The identification of novel drug-target interactions is a labor-intensive and low-throughput process. In silico alternatives have proved to be of immense importance in assisting the drug discovery process. Here, we present TransDTI, a multiclass classification and regression workflow employing transformer-based language models to segregate interactions between drug-target pairs as active, inactive, and intermediate. The models were trained with large-scale drug-target interaction (DTI) data sets, which reported an improvement in performance in terms of the area under receiver operating characteristic (auROC), the area under precision recall (auPR), Matthew’s correlation coefficient (MCC), and R2 over baseline methods. The results showed that models based on transformer-based language models effectively predict novel drug-target interactions from sequence data. The proposed models significantly outperformed existing methods like DeepConvDTI, DeepDTA, and DeepDTI on a test data set. Further, the validity of novel interactions predicted by TransDTI was found to be backed by molecular docking and simulation analysis, where the model prediction had similar or better interaction potential for MAP2k and transforming growth factor-β (TGFβ) and their known inhibitors. Proposed approaches can have a significant impact on the development of personalized therapy and clinical decision making.For an energy-intensive sweetening process, it is common that sour gases from different sources are sent to a single sweetening plant in industries. In our previous work, a multiple gas feed sweetening process was proposed, which can simultaneously improve the purity of H2S and reduce the energy consumption of the plant. This study aims to develop the superstructure of that process and use a simulation-based optimization framework with Aspen HYSYS as the process simulator and particle swarm optimization algorithm as the optimizer. In addition, by taking full advantage of the robustness of the built-in algorithm of the simulator, the convergence of the model is improved; meanwhile, simplification of the process and reduction of the optimization time are accessible with the proposed design specifications and assumptions. For a convergence-difficult column, a stepwise convergence adjustment was used to ensure their convergence. Based on this, the robustness and effectiveness of the method is proven through a case study, and it can also provide guidance for model selection, process simplification, and optimization of the same type of absorption process.The gas-liquid contact area can be increased by the gas-liquid swirl flow, and the heat and mass transfer efficiency between gas and liquid can be enhanced by the gas-liquid swirl flow. The gas hydrate formation can be promoted by the swirl flow. The swirl flow can ensure the safety of the natural gas hydrate slurry. The flow pattern and conversion law of gas-liquid swirl with a twist tape should be investigated, and numerical simulation has been carried out by using the Reynolds stress model and the level set model. As a result, four different flow patterns are obtained, namely, swirl-stratified flow, swirl bubble flow, swirl slug flow, and swirl annular flow. The influence of gas-liquid-phase velocity on the flow pattern is investigated. The drag force generated by the two-phase slip velocity can change the gas form. At the same time, the flow pattern at different positions of the pipe will also change because of the attenuation of the swirl flow. Finally, the flow pattern map of the gas-liquid swirl flow is accomplished, and it is compared with the Mandhane flow pattern map. The flow boundary of the swirl bubble flow and the swirl annular flow is predicted.Theory and computer simulation studies have predicted that water molecules around hydrophobic molecules should undergo an order-disorder transition with increasing solute size around a 1 nm length scale. Some theories predict the formation of a clathrate-like ordered structure around smaller hydrophobic solutes (1 nm) and surfaces. Experimental validation of these predictions has often been elusive and contradictory. High-resolution Raman spectroscopy has detected that water around small hydrophobic solutes shows a signature similar to that of bulk water at lower temperature (increased ordering and a stronger hydrogen-bonded network). Similarly, water around larger solutes shows an increasing population of dangling OH bonds very similar to higher temperature bulk water. Thus, the solute size dependence of the structure and dynamics of water around hydrophobic molecules seems to have an analogy with the temperature dependence in bulk water. In this work, using atomistic classical molecular dynamics (MD) simulaon.Hydroxymethylsilanetriol undergoes condensation reactions to form new structures with an organic part in the formed bridges. As a first step to explore the formation of these bridges, we studied the corresponding mechanisms using simple models and theoretical methods. Three mechanisms were studied for the formation of dimers of hydroxymethylsilanetriol with bridges Si-O-C-Si, Si-O-Si, and Si-C-O-C-Si. Energies are calculated using M06/6-311+G(d,p) single-point calculations on B3LYP-optimized geometries in solution and including B3LYP thermodynamic corrections. The first mechanism for the formation of the Si-O-C-Si bridge consists of one step. The second mechanism for the formation of the Si-O-Si bridge consists of two steps. The barrier for the last mechanism for the formation of the Si-C-O-C-Si bridge is too high and cannot occur at room temperature. The energy barriers are 31.8, 27.6, and 65.9 kcal mol-1 for the first, second, and third mechanisms, respectively. When adding one explicit water molecule, these energies are 25.9, 22.9, and 80.3 kcal mol-1, respectively. The first and second mechanisms can occur at room temperature, which is in agreement with the experimental results.A prion’s pathogenic character is enciphered in its conformation, which also defines the chemical environments of its amino acids. Differences in chemical environments influence the reactivity of amino acid side chains, in a conformation-dependent manner. Chemical oxidation of susceptible methionines would identify those methionines on the surface of a prion, which would reveal conformation-dependent information. We identified a set of methionine-containing peptides derived from the tryptic, chymotryptic, or tryptic/chymotryptic digestion of recombinant prion protein and the Sc237 strain of hamster-adapted scrapie. We developed a multiple reaction monitoring-based method of quantifying the extent of the methionine oxidation in those peptides. This approach can be used to define a prion’s conformation and to distinguish among prion strains, which is an important component of food safety.The optical manipulation of nanoscale objects via structured light has attracted significant attention for its various applications, as well as for its fundamental physics. In such cases, the detailed behavior of nano-objects driven by optical forces must be precisely predicted and controlled, despite the thermal fluctuation of small particles in liquids. In this study, the optical forces of an optical vortex acting on gold nanoparticles (Au NPs) are visualized using dark-field microscopic observations in a nanofluidic channel with strictly suppressed forced convection. Manipulating Au NPs with an optical vortex allows the evaluation of the three optical force components, namely, gradient, scattering, and absorption forces, from the in-plane trajectory. We develop a Langevin dynamics simulation model coupled with Rayleigh scattering theory and compare the theoretical results with the experimental ones. Experimental results using Au NPs with diameters of 80-150 nm indicate that our experimental method can determine the radial trapping stiffness and tangential force with accuracies on the order of 0.1 fN/nm and 1 fN, respectively. Our experimental method will contribute to broadening not only applications of the optical-vortex manipulation of nano-objects, but also investigations of optical properties on unknown nanoscale materials via optical force analyses.The materials science community has been increasingly interested in harnessing the power of deep learning to solve various domain challenges. However, despite their effectiveness in building highly predictive models, e.g., predicting material properties from microstructure imaging, due to their opaque nature fundamental challenges exist in extracting meaningful domain knowledge from the deep neural networks. In this work, we propose a technique for interpreting the behavior of deep learning models by injecting domain-specific attributes as tunable „knobs” in the material optimization analysis pipeline. By incorporating the material concepts in a generative modeling framework, we are able to explain what structure-to-property linkages these black-box models have learned, which provides scientists with a tool to leverage the full potential of deep learning for domain discoveries.Electrical power can be extracted from interactions at the interface of water/materials, known as the „hydrovoltaic” phenomenon. Devices based on this emerging technology hold a lot of promise for meeting renewable energy demands, but materials reported to date largely require specific weather conditions, such as low humidity (∼10-30%), thus hindering widespread application. Herein, we report a new use of plates for thin layer chromatography (TLC) that provide a continuous support of capillary-driven water flow. When coated with α-Al2O3, this simple 8 cm2 device can produce a continuous voltage of ∼0.33 V and a short circuit current of ∼0.85 μA over a wide range of humidity (10-90%). Low cost, stability against surface reactions, ease of fabrication, and power output under varied weather conditions make this device a realistic possibility for use in renewable power generation applications.In metal-N-C systems, doped metals have an obvious valence change in the process of Li-ion deintercalation, which is in agreement with the operational principle of traditional anode materials. Doped metals will transfer some electrons to the neighboring N atoms to improve the valence state. Along with Li adsorption, the charge transferred to the nearest N or C from Li is less compared to that transferred to the doped metal. Hence, doped metals have an obvious valence change in the process of Li-ion deintercalation, and doped N just serves as a container for holding electrons. The local states of C and N p electrons in the Co-N-C structure can be fully destroyed, which can effectively improve the electronic properties of graphene.Four complexes from lanthanides, 3-pyridylacetate, and 1,10-phenanthroline, formulated as [Ln2(3-PAA)2(μ-Cl)2(phen)4](ClO4)2 [Ln = Gd(1), Dy(2), Eu(3), Tb(4), 3-PAA = 3-pyridylacetic acid, phen = 1,10-phenanthroline], were obtained. The four compounds were characterized by IR spectra, thermogravimetric analyses, powder X-ray diffraction, and single-crystal X-ray diffraction. Compounds 1-4 are isomorphous, and they have a dinuclear structure. Magnetic studies reveal that 1 shows the magnetocaloric effect with -ΔS m max = 19.03 J kg-1 K-1 at 2 K for ΔH = 5 T, and 2 displays a field-induced single-molecule magnet with U eff = 19.02 K. The photoluminescent spectra of 3 and 4 exhibit strong characteristic emission, which demonstrate that the ligand-to-EuIII/TbIII energy transfer is efficient.Colchicine, the main active alkaloid from Colchicum autumnale L., is a potent tubulin binder and represents an interesting lead structure for the development of potential anticancer chemotherapeutics. We report on the synthesis and investigation of potentially reactive colchicinoids and their surprising biological activities. In particular, the previously undescribed colchicinoid PT-100, a B-ring contracted 6-exo-methylene colchicinoid, exhibits extraordinarily high antiproliferative and apoptosis-inducing effects on various types of cancer cell lines like acute lymphoblastic leukemia (Nalm6), acute myeloid leukemia (HL-60), Burkitt-like lymphoma (BJAB), human melanoma (MelHO), and human breast adenocarcinoma (MCF7) cells at low nanomolar concentrations. Apoptosis induction proved to be especially high in multidrug-resistant Nalm6-derived cancer cell lines, while healthy human leukocytes and hepatocytes were not affected by the concentration range studied. Furthermore, caspase-independent initiation of apoptosis via an intrinsic pathway was observed. PT-100 also shows strong synergistic effects in combination with vincristine on BJAB and Nalm6 cells. Cocrystallization of PT-100 with tubulin dimers revealed its (noncovalent) binding to the colchicine-binding site of β-tubulin at the interface to the α-subunit. A pronounced effect of PT-100 on the cytoskeleton morphology was shown by fluorescence microscopy. While the reactivity of PT-100 as a weak Michael acceptor toward thiols was chemically proven, it remains unclear whether this contributes to the remarkable biological properties of this unusual colchicinoid.Etoposide (VP-16) is used for the treatment of various cancers, including nasopharyngeal carcinoma (NPC); however, cancers develop resistance to this agent by promoting DNA repair. The DNA-PK (DNA-PKcs) catalytic subunit and poly(ADP-ribose) polymerase 1 (PARP1) mediate acquired resistance and poor survival in NPC cells exposed to DNA damaging agents. DNA repair can alter the sensitivity of NPC cells to DNA damaging agents, and these two enzymes function concomitantly in response to DNA damage in vivo. Therefore, we explored the relationship between DNA-PKcs and PARP1, which may affect NPC cell survival by regulating DNA repair after VP-16 treatment. We performed quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunoassays and found that DNA-PKcs knockdown downregulated the PARP1 and PAR expression. Conversely, PARP1 knockdown reduced DNA-PKcs activity, indicating the mutual regulation between DNA-PKcs and PARP1 in VP-16-induced DNA repair. Moreover, a combination treatment with olaparib (a PARP1 inhibitor) and NU7441 (a DNA-PKcs inhibitor) sensitized NPC cells to VP-16 in vitro and in vivo, suggesting that the combined treatment of olaparib, NU7441, and a DNA-damaging agent may be a successful treatment regimen in patients with NPC.Examples on the real-world field application of Raman spectroscopy with systematic analysis of the intensity variation of D and G bands corresponding to the change of excitation laser energy to characterize and compare coke species from various industrial processes are presented. The findings indicate the different degree of sp2 and sp3 hybridized bonding structures of amorphous carbon collected from different industrial processes as well as heavy carbonaceous deposits generated by industrial catalysts. This spectroscopic methodology is practical and highly beneficial in identifying coke formation mechanisms in industrial processes, as well as supporting design strategies to abate the undesired coke formation on industrial catalysts.157Gd (natural abundance = 15.7%) has the highest thermal neutron capture cross section (σ) of 254,000 barns (1 barn = 10-28 m2) among stable (nonradioactive) isotopes in the periodic table. Another stable isotope, 155Gd (natural abundance = 14.8%), also has a high σ value of 60,700 barns. These σ values are higher than that of 10B (3840 barns, natural abundance = 19.9%), which is currently used as a neutron-absorbing isotope for boron neutron capture therapy agents. Energetic particles such as electrons and γ-rays emitted from Gd-isotopes after neutron beam absorption kill cancer cells by damaging DNAs inside cancer-cell nuclei without damaging normal cells if Gd-chemicals are positioned in cancer cells. To date, various Gd-chemicals such as commercial Gd-chelates used as magnetic resonance imaging contrast agents, modified Gd-chelates, nanocomposites containing Gd-chelates, fullerenes containing Gd, and solid-state Gd-nanoparticles have been investigated as gadolinium neutron capture therapy (GdNCT) agents. All GdNCT agents had exhibited cancer-cell killing effects, and the degree of the effects depended on the GdNCT agents used. This confirms that GdNCT is a promising cancer therapeutic technique. However, the commercial Gd-chelates were observed to be inadequate in clinical use because of their low accumulation in cancer cells due to their extracellular and noncancer targeting properties and rapid excretion. The other GdNCT agents exhibited higher accumulation in cancer cells, compared to Gd-chelates; consequently, they demonstrated higher cancer-cell killing effects. However, they still displayed limitations such as poor specificity to cancer cells. Therefore, continuous efforts should be made to synthesize GdNCT agents suitable in clinical applications. Herein, the principle of GdNCT, current status of GdNCT agents, and general design strategy for GdNCT agents in clinical use are discussed and reviewed.Various functional chemical materials have been widely used in imaging and tumor therapy. Targeted ligands such as antibodies, peptides, and small molecules have been combined with functional materials to enhance cellular uptake and are used for active targeting of cancer cells and tumors. Among them, phenylboronic acid (PBA), as a small molecular ligand, has the characteristics of low cytotoxicity and easy modification. PBA improves the cancer cell imaging and tumor treatment effect by binding to glycans on the surface of cancer cells. In this Mini-Review, we introduced the modification strategy and targeting strategy of PBA. We focused on the applications of PBA-based functional materials in fluorescence imaging and tumor therapy. For fluorescence imaging, the potential of PBA-based functional chemical materials in cancer diagnosis and tumor targeting was proved by cell imaging and in vivo imaging. For tumor therapy, we mainly discussed the applications of PBA-based functional chemical materials in chemotherapy, gene therapy, phototherapy, and immunotherapy. PBA-based functional chemical materials provide a useful method for cancer diagnosis and treatment.Artificial intelligence (AI) and machine learning (ML) are transforming industries, where low-cost, big data can utilize computing power to optimize system performance. Oil and gas (O&G) fields are getting mature, where well integrity (WI) problems become more common and field operations are now more challenging. Hence, they are good candidates for transformation due to the low cost of data storage, highlighting the oil market decline, along with dynamic risk posed during operations. This paper is presenting a comprehensive compilation of different ML applications in diverse disciplines of the petroleum industry. The pool of AI and ML with respect to different areas of applications along with publication years has been categorized. The main focus of this study is classifying well integrity failures where the authors found that the potential of AI and ML in predicting well integrity failures has not been efficiently tapped, and there is an explicit gap in the literature. First, the applications of AI, ML, and data analytics in the O&G industry are discussed thoroughly, so this paper can be a comprehensive reference for readers and future researchers. Then data preprocessing is explained. This includes data gathering, cleaning, and feature engineering. Next, the different ML models are compared and discussed. Finally, model performance evaluation and best model selection are described. This study would be a concrete foundation in the design and construction of ML programs that can be deployed for WI risk management. The developed model can be simply used for any well stock, providing quick and easy assessment instead of subjective and tedious assessment. The layout can be simply adjusted to reflect the risk profile of any well type or any field.Epilepsy is a chronic neurological disorder in the brain, affecting individuals of all age groups. Nearly 1% of the world population is affected by seizure disorder, of which 80% of the patients are observed in underdeveloped and developing countries. The predominant treatment option for epilepsy includes an antiepileptic drug named brivaracetam. This drug emerged as an unusual success of rational drug discovery in clinical development by exhibiting magnificent affinity toward synaptic vesicle glycoprotein as compared to conventional drug levetiracetam and piracetam. Given its efficiency in limiting the progression of epilepsy, this drug has drawn considerable attention of researchers to devise novel routes of its synthesis. The present review encapsulates the reported literature on synthetic strategies for brivaracetam, which will assist medicinal chemists in the further progress of its synthesis.On September 10, 2021, a special tribunal established by the French government launched an inquiry into the activities of former health minister Dr. Agnes Buzyn who was charged with „endangering the lives of others”. It is surprising to learn of this accusation and inquiry into the actions of a public health official whose response to the epidemic was, to all appearances, exemplary.Ureteroiliac fistula is a rare complication associated with ureteral stenting and iliac artery reconstruction and can lead to life-threatening hemorrhage. We report a case of acute bleeding from a ureteroiliac fistula in an 89-year-old man with bladder cancer who had undergone pelvic radiation, radical cystectomy, and ileal conduit complicated by ureteral strictures requiring routine stent exchanges. Multidisciplinary diagnostic therapies revealed the fistula, which was treated with hypogastric artery coiling and covered stent placement. No further bleeding issues had resulted from the fistula at 11 months of follow-up. The presence of a ureteroiliac fistula should be considered in any patient with a similar history.Middle aortic syndrome presents with segment narrowing of the descending thoracic and abdominal aorta. A common manifestation is uncontrolled hypertension, which can lead to severe aortic regurgitation in the long term. We have presented the case of a 31-year-old woman with worsening heart failure symptoms and longstanding uncontrolled hypertension. Echocardiography revealed severe aortic regurgitation. Aortic computed tomography showed severe stenosis of the aorta at the diaphragm level. Stent graft implantation was performed, followed by Bentall surgery 1 year later. Endovascular stent graft implantation of the descending aorta can be used safely as a bridging surgery for the Bentall procedure to reduce the patient’s blood pressure and relieve heart failure symptoms.Lymphoceles result from either trauma to the lymphatic vessels or after vein graft harvest, which occurs in 10% to 16% of patients. When a lymphocele persists despite conservative treatment, patients can experience undue distress. We have reported the case of successful treatment using lymphatic venous anastomosis (LVA) of an intractable lymphocele that had been refractory to conservative treatment, including stretch bandaging, drainage, and local injection for 2 years after great saphenous vein harvest. The lymphocele resolved shortly after the LVA without any adverse effects. LVA can be a useful and minimally invasive alternative treatment of lymphocele after harvesting the great saphenous vein.Vascular closure devices have become more popular in some clinical settings because they allow for quicker hemostasis and earlier ambulation. Although these devices have several benefits compared with manual compression, errors in deployment can result in a multitude of complications. We have presented two cases in which the Celt arterial closure device was maldeployed and caused significant patient morbidity.Pathogenic fungi hide from their hosts by camouflage, obscuring immunogenic cell wall components such as beta-glucan with innocuous coverings such as mannoproteins and alpha-glucan that are less readily recognised by the host. Attempts to understand how such processes are regulated have met with varying success. Typically studies focus on understanding the transcriptional response of fungi to either their reservoir environment or the host. However, such approaches do not fully address this research question, due to the layers of post-transcriptional and post-translational regulation that occur within a cell. Although in animals the impact of post-transcriptional and post-translational regulation has been well characterised, our knowledge of these processes in the fungal kingdom is more limited. Mutations in RNA-binding proteins, like Ssd1 and Candida albicans Slr1, affect cell wall composition and fungal virulence indicating that post-transcriptional regulation plays a key role in these processes. Here, we review the current state of knowledge of fungal post-transcriptional regulation, and link this to potential mechanisms of immune evasion by drawing on studies from model yeast and plant pathogenic fungi. We highlight several RNA-binding proteins that regulate cell wall synthesis and could be involved in local translation of cell wall components. Expanding our knowledge on post-transcriptional regulation in human fungal pathogens is essential to fully comprehend fungal virulence strategies and for the design of novel antifungal therapies.

Radiation therapy (RT)-associated lymphopenia may adversely affect treatment outcomes, particularly in the era of immunotherapy. We sought to determine dosimetric factors correlated with lymphopenia after palliative RT in a cohort of patients with advanced cancer treated with anti-PD-1 immune checkpoint inhibitors.

We included patients with metastatic lung cancer, melanoma, or renal cell carcinoma who were treated with either pembrolizumab or nivolumab and received palliative RT to an extracranial site. Baseline and nadir absolute lymphocyte counts (ALCs) within 6 weeks of RT were recorded. Dosimetric factors were extracted from the corresponding dose-volume histograms and also used to model the dose to circulating lymphocytes via a whole-body blood flow model that simulates the spatiotemporal distribution of blood particles in major organs during RT.

We analyzed 55 patients who underwent 80 total courses of palliative RT; most (94%) were treated with 3-dimensional conformal RT. Doses to the whole body,tting.

The RT dose to the whole body, bone, and LBVs and the modeled dose to circulating lymphocytes were correlated with lymphopenia in patients treated with palliative RT and anti-PD-1 immune checkpoint inhibitors. These findings may inform future radiation planning in this setting.

To report 3 otherwise healthy patients with Herpes zoster reactivation shortly after administration of a mRNA vaccine against the novel COVID-19 virus.

Patient 1 is a 54 year old who presented with Herpes zoster meningitis complicated by enhancing nodular leptomeningeal lesions of the spinal cord. The subsequent two patients had Herpes zoster ophthalmicus of the cornea (Case 2) and eyelid (Case 3). All three presented within 2 weeks of receiving the Pfizer/BioNTech COVID-19 vaccine.

Herpes zoster may be a side effect of m RNA vaccination against the Sars-CoV2 vaccine and requires further investigation.

Herpes zoster may be a side effect of m RNA vaccination against the Sars-CoV2 vaccine and requires further investigation.

Covid-19 has profoundly affected the day-to-day lives of individual citizens. It has strained all aspects of health care including eye banking and corneal transplantation. Although elective procedures like optical Keratoplasty can be postponed, management of perforating ulcers needs tectonic Keratoplasty to avoid permanent ocular morbidities. It has become inevitable for corneal surgeons to innovate newer methods of treatment for such corneal diseases. The large corneal perforations if left untreated may lead to permanent visual loss. An alternative method of managing a large peripheral corneal perforation of size 5×5.5 mm was done using Tenons patch graft with Gore-tex in a 50-year-old female patient, during the lockdown.

Tenons graft with Gore-tex, effectively sealed the large corneal perforation in our case without iris incarceration, favourable for future visual rehabilitation.

Tenons and Gore-tex are readily available. It is not necessary to rely on the donor corneas or the distributing eye banks during this pandemic situation. In the future, this procedure can reduce the burden of the pre-existing increase in the gap between the need and supply of donor corneas in developing countries.

Tenons and Gore-tex are readily available. It is not necessary to rely on the donor corneas or the distributing eye banks during this pandemic situation. In the future, this procedure can reduce the burden of the pre-existing increase in the gap between the need and supply of donor corneas in developing countries.Polycyclic, highly fused and, perforce, highly conjugated aromatic organic compounds (PACs) have been of interest to chemists since the discovery of naphthalene in 1821. In modern decades these have attracted ever-growing attention because of their architectures, properties, and wide-ranging practical applications (cf. The Bigger Picture). Given the unabated interest in such molecules, the development of new methods and strategies for the practical synthesis of PACs having new structural motifs is important. Here we describe one-pot, purely thermal cyclizations of substrates containing sets of independent triynes, each arrayed upon a common core structure. This produces topologically unique products through sequential generation/trapping of a series of benzyne intermediates. More specifically, these all conform to processes that can be considered as radial-hexadehydro-Diels-Alder (HDDA) reactions. The late-stage and de novo creation of multiple arenes in these multi-benzyne processes constitutes a fundamentally new synthetic strategy for constructing novel molecular topologies.

Dyskeratosis congenita (DC) is a rare disease and is a heterogenous disorder, with its inheritance patterns as autosomal dominant, autosomal recessive, and X-linked recessive. This disorder occurs due to faulty maintenance of telomeres in stem cells. This congenital condition is diagnosed with three symptoms oral leukoplakia, nail dystrophy, and abnormal skin pigmentation. However, because it has a wide range of symptoms, it may have phenotypes similar to other diseases. For this reason, it is necessary to use methods of measuring the Telomere Length (TL) and determining the shortness of the telomere in these patients so that it can be distinguished from other diseases. Today, the Next Generation Sequencing technique accurately detects mutations in the target genes.

This work aims to review and summarize how each of the DC genes is involved in TL, and how to diagnose and differentiate the disease using clinical signs and methods to measure TL. It also offers treatments for DC patients, such as Hematopoietic Stem Cell Transplantation and Androgen therapy.

In DC patients, the genes involved in telomere homeostasis are mutated. Because these patients may have an overlapping phenotype with other diseases, it is best to perform whole-exome sequencing after genetics counseling to find the relevant mutation. As DC is a multi-systemic disease, we need to monitor patients frequently through annual lung function tests, ultrasounds, gynecological examinations, and skin examinations.

In DC patients, the genes involved in telomere homeostasis are mutated. Because these patients may have an overlapping phenotype with other diseases, it is best to perform whole-exome sequencing after genetics counseling to find the relevant mutation. As DC is a multi-systemic disease, we need to monitor patients frequently through annual lung function tests, ultrasounds, gynecological examinations, and skin examinations.

Tobacco use is one of the most important causes of obstetric and perinatal pathologies. Its frequency during pregnancy is high and could be related to various socioeconomic and cultural characteristics of the mothers.

The aim of this study is to determine the trend and prevalence of smoking in pregnant mothers in our area over the years and the socio-cultural or obstetric factors associated with smoking as well as the repercussions on the newborns related to its consumption.

Retrospective study of 18,959 mothers of healthy newborns in the maternity ward of the regional hospital during the years 2002-2019. The variable under study was maternal smoking during pregnancy compared with various maternal, obstetric, and perinatal factors.

A mean percentage of 20.4% of the mothers smoked, with significantly decreasing percentages over the years. There was a significant association between smoking and mothers’ age, origin, level of education, the occurrence of previous abortions, parity, type of breastfeeding at discharge, type of delivery, low birth weight, and need for neonatal resuscitation.

This defines a profile of pregnant smokers on whom it is important to act young, Spanish, with a low level of education, multiparous, and with previous miscarriages. Its repercussions are also evident with a lower birth weight in newborns. Knowledge of these factors will make it possible to design more effective intervention strategies to reduce smoking during pregnancy.

Any effort that reduces smoking habits can improve the health status of mothers and newborns and the first step is to know who are risk pregnants.

Any effort that reduces smoking habits can improve the health status of mothers and newborns and the first step is to know who are risk pregnants.

Recent studies suggest that the prevalence of cardiac involvement in young competitive athletes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears to be low.

This study aimed to determine the prevalence of cardiovascular involvement in young competitive athletes.

In this single-center retrospective cohort study from one Division I university; we assessed the prevalence of cardiovascular involvement among collegiate athletes who tested positive for SARS-CoV-2 by polymerase chain reaction testing. Data were collected from June 25, 2020, to May 15, 2021. The primary outcome was the prevalence of cardiac involvement based on a comparison of pre- and post-infection electrocardiogram (ECGs). The secondary outcome was to evaluate for any association between ethnicity and the presence or absence of symptoms.

Among 99 athletes who tested positive for the SARS-CoV-2 virus (mean age 19.9 years [standard deviation 1.7 years]; 31% female), baseline ECG changes suggestive of cardiovs.

To compare the impact of COVID-19 pandemic on 2-[

F]FDG PET/CT imaging work-flow during the three waves in a medical institution of southern of Italy.

We retrospectively reviewed the numbers and results of 2-[

F]FDG PET/CT studies acquired during the following three periods of the COVID-19 waves 1) February 3-April 30, 2020; 2) October 15, 2020-January 15, 2021; and 3) January 18-April 16, 2021.

A total of 861 PET/CT studies in 725 patients (388 men, mean age 64 ± 4 years) was acquired during the three waves of COVID-19 pandemic. The majority (94%) was performed for diagnosis/staging (n = 300) or follow-up (n = 512) of neoplastic diseases. The remaining 49 studies (6%) were acquired for non-oncological patients. The distribution of number and type of clinical indications for PET/CT studies in the three waves were comparable (p = 0.06). Conversely, the occurrence of patients positive for COVID-19 infection progressively increased (p < 0.0001) from the first to third wave; in particular, patients with COVID-19 had active infection before PET/CT study as confirmed by molecular oro/nasopharyngeal swab.

Despite the restrictive medical measures for the emergency, the number of 2-[

F]FDG PET/CT studies was unchanged during the three waves guaranteeing the diagnostic performance of PET/CT imaging for oncological patients.

Despite the restrictive medical measures for the emergency, the number of 2-[18F]FDG PET/CT studies was unchanged during the three waves guaranteeing the diagnostic performance of PET/CT imaging for oncological patients.Steam inhalation therapy can be a contemporary approach for COVID-19 affected patients of all age groups to manage respiratory conditions, though it presently lacks the scientific backing to establish itself as a befitting practice. The age of COVID-19 has facilitated this traditional home remedy to resurface among the general mass as a helpful approach for the prevention and adjuvant treatment of the disease. In this review, the means of SARS-CoV-2 infection and impact of the parameters, namely steam inhalation and heat on such infection has been delineated via enumerating the effect of the parameters in the human body and against SARS-CoV-2. The literature search was conducted using PubMed, Web of Science, Scopus, ScienceDirect, Wiley Online Library, Google Scholar, and CNKI Scholar databases. The keywords used in the survey include 'Steam inhalation’, 'SARS-CoV-2′, 'COVID-19′, 'Clinical study’, 'Mechanism of action’, 'Traditional uses’, 'Phytochemistry’ and 'Adverse effects’. Clinical studies concerning steam inhalation by COVID-19 patients have been comprehended to demarcate the scientific obscurity of the practice. The safety profile of the procedure has also been outlined emphasizing evading measures against COVID-19 and other related disease states. To recapitulate, application of the steam inhalation with herbal concoctions and phytochemicals having folkloric prevalence as an inhalable remedy against respiratory illnesses has been explored in this review work to focus on a new aspect in the COVID-19 treatment paradigm using steam and progress of further research hither.

The study aimed to investigate the osteogenic ability of bioactive glass (bioglass) combined with recombinant human bone morphogenetic protein-9 (rhBMP-9) on rat bone marrow mesenchymal stem cells (BMSCs) in vitro. The study also compares bone regeneration using rhBMP9 soaked with different carrier systems, including bioglass or collagen membranes (BioGide, BG) in a rat alveolar bone site preservation model in vivo.

Scanning electron microscopy was employed to analyze bioglass surface. The absorption and release potential of rhBMP9 from bioglass were researched by ELISA.The cell viability, adhesion, proliferation, and differentiation were assessed for rhBMP9 soaked on bioglass by cck-8 kit, alkaline phosphatase (ALP) activity assay, alizarin red staining, and real-time PCR. Furthermore, prepared grafts (bioglass + BG, bioglass/rhBMP9+BG, and bioglass + BG/rhBMP9) were implanted into the maxillary right first incisor sockets of Sprague Dawley rats for 8 weeks, and new bone formation was quantified by microgating site preservation effect after tooth extraction when associated with rhBMP9 and provides a practical clinical solution to the problem of bone deficiency caused by alveolar bone atrophy.

Both bioglass and BG can be applied in GBR surgery as effective carriers of rhBMP9. However, BG may be more suitable than bioglass for investigating site preservation effect after tooth extraction when associated with rhBMP9 and provides a practical clinical solution to the problem of bone deficiency caused by alveolar bone atrophy.The diffusion phenomena of sucrose and lactitol in cherries using different proportions during osmotic dehydration was quantified by means of a mathematical model based on Fick’s second law. The average effective diffusion coefficient for soluble solids in skin and flesh are 5.37 10-11 m2∕s and 1.24 10-10 m2∕s. Whereas, for water in skin and flesh are 9.27 10-09 m2∕s and 5.48 10-08 m2∕s. A significant difference for water diffusion coefficients (p less then 0.05) was observed between the treatments. This could indicate that the diffusion between species and treatments is differential. Effective diffusion coefficients for water in skin and flesh are 2 orders of magnitude greater than effective diffusion coefficients for soluble solids. This is probably due to its lesser molecular weight. Furthermore, the effective diffusion coefficients for water and soluble solids in cherry skin are between 1 and 2 orders of magnitude lower than effective diffusion coefficients for both in cherry flesh, possibly due to the barrier effect exerted by the cherry skin.Sacha inchi seed oil is a promising substance for applications in food, pharmaceutical, and nutraceutical industries because of its valuable components, particularly omega-3. In this research, sacha inchi oil was extracted from the seed kernels using supercritical carbon dioxide (CO2) extraction compared with Soxhlet extraction. The influences of extraction time, type of solvents (hexane, ethanol, butanol, and i-propanol), and solvent volume on the oil yield and compositions were investigated in the Soxhlet. In the supercritical CO2 extraction, the effects of extraction time, temperature, and pressure were evaluated. The physicochemical properties of sacha inchi oils extracted with supercritical CO2 were characterized. Scanning electron microscopy (SEM) equipped with energy dispersive X-ray analysis (EDX), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) were also carried out. The results showed the advantage of using supercritical CO2 extraction to increase the omega-3 content in the extracted oil within a shorter extraction time. The omega-3 content of 46.08% was obtained from the supercritical CO2 extraction at 400 bar and 60 °C. Supercritical CO2 extraction is a safe and environmentally friendly method that yields a toxic-free oil.Currently available screening instruments for evaluation of individuals with intellectual disabilities do not capture all the complications associated with Down Syndrome (DS). Here, we examined age and gender-specific variability revolving around major challenges related to ophthalmologic and auditory health, social integration, daily life, and behavioral problems in 468 (age 2-84 years) individuals with DS living in all eight divisions of Bangladesh. More than half of the children presented with significant difficulty in walking or other targeted movements compared with 37.9% of adolescents (p = 0.03). Nearly 70% of children exhibited communication difficulties, particularly revolving around the understanding of speech, comprehending or learning tasks or new materials, and in expressing thoughts in words or behaviors (p = 0.003-0.006). Uncontrolled urination was frequent and predominantly found among children (p = 0.04). No significant differences were present in females vs. males except for concern about physical appearance (females 58.5% vs. males 47.5%; p = 0.02). The severity of DS was associated with intellectual performance, communication difficulties, and self-sufficiency (i.e., uncontrolled micturition or bowel movements) but not with psychotic, ophthalmologic, auditory, or motor skills-related problems. Increased awareness of DS phenotypic profiles among professionals and caregivers can foster earlier detection and counselling and help formulate appropriate interventions to reduce long-term sequelae and enhance cognitive and behavioral developmental outcomes.Complex problem solving (CPS) is considered an important educational outcome in the 21st century. Despite its importance, we have only little only knowledge of its measurability, development, or comparability in some countries, in particular in those with a short history of computer-based assessment. The results of the current study provide insights into the validity of CPS measurements and shed light on the different behavioral patterns and test-taking behavior in two convenience samples with different sample characteristics of Jordanian (N = 431) and Hungarian (N = 1844) students as they solve complex problems. CPS proved to be measurement-invariant in Jordan and Hungary among university students. Analyzing log data, we identified differences in students’ test-taking behavior in terms of the effectiveness of their exploration strategy, time-on-task, and number of trials. Based on the students’ exploration strategy behavior, we identified four latent classes in both samples. The tested process indicators proved to be non-invariant over the different latent profiles; that is, there are differences in the role of the number of manipulations executed, time-on-task, and type of strategy used in actual problem-solving achievement between students that fall within different profiles. This study contributes to our understanding of how students from different educational contexts behave while solving complex problems.

Perfluorooctanoic acid (PFOA) is an environmental contaminant associated with adverse metabolic outcomes in developmentally exposed human populations and mouse models. Hexafluoropropylene oxide-dimer acid (HFPO-DA, commonly called GenX) has replaced PFOA in many industrial applications in the U.S. and Europe and has been measured in global water systems from <1 to 9350 ng/L HFPO-DA. Health effects data for GenX are lacking.

Determine the effects of gestational exposure to GenX on offspring weight gain trajectory, adult metabolic health, liver pathology and key adipose gene pathways in male and female CD-1 mice.

Daily oral doses of GenX (0.2, 1.0, 2.0 mg/kg), PFOA (0.1, 1.0 mg/kg), or vehicle control were administered to pregnant mice (gestation days 1.5-17.5). Offspring were fed a high- or low-fat diet (HFD or LFD) at weaning until necropsy at 6 or 18 weeks, and metabolic endpoints were measured over time. PFOA and GenX serum and urine concentrations, weight gain, serum lipid parameters, body mass coes adverse metabolic outcomes in adult mice that are diet- and sex-dependent. GenX also accumulated in pup serum, suggesting that placental and potentially lactational transfer are important exposure routes for GenX.

Prenatal exposure to 1 mg/kg GenX and 1 mg/kg PFOA induces adverse metabolic outcomes in adult mice that are diet- and sex-dependent. GenX also accumulated in pup serum, suggesting that placental and potentially lactational transfer are important exposure routes for GenX.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the leading causes of cancer-related deaths in the world. For patients with PDAC who are not eligible for surgery, radiation therapy improves local disease control, yet safely delivering therapeutic doses of radiation remains challenging due to off-target toxicities in surrounding normal tissues. NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide crystalline nanoparticles, has recently shown clinical activity in soft tissue sarcoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, and advanced solid malignancies with lung or liver metastases. Here we report the first patient with pancreatic cancer treated with NBTXR3.

A 66-year-old male with unresectable locally advanced PDAC was enrolled on our clinical trial to receive NBTXR3 activated by radiation therapy. Local endoscopic delivery of NBTXR3 was followed by intensity modulated radiation therapy (IMRT). Follow-up assessment consisted of physical examination, laboratory studies including CA19-9, and CT of the chest, abdomen, and pelvis.

The patient received NBTXR3 by local endoscopic delivery without any acute adverse events. Radiation treatment consisted of 45Gy in 15 daily fractions using IMRT. The patient began radiation twelve days after NBTXR3 injection. Daily CT-on-rails imaging demonstrated retention of NBTXR3 within the tumor for the duration of treatment. At initial follow-up evaluation, the lesion remained radiographically stable and the patient did not demonstrate treatment-related toxicity.

This report demonstrates initial feasibility of local endoscopic delivery of NBTXR3 activated by radiation therapy for patients with pancreatic cancer who are not eligible for surgery.

This report demonstrates initial feasibility of local endoscopic delivery of NBTXR3 activated by radiation therapy for patients with pancreatic cancer who are not eligible for surgery.The microbial model of mammalian drug metabolism, Cunninghamella elegans, has three cytochrome P450 reductase genes in its genome g1631 (CPR_A), g4301 (CPR_B), and g7609 (CPR_C). The nitroreductase activity of the encoded enzymes was investigated via expression of the genes in the yeast Pichia pastoris X33. Whole cell assays with the recombinant yeast demonstrated that the reductases converted the anticancer drug flutamide to the nitroreduced metabolite that was also produced from the same substrate when incubated with human NADPH cytochrome P450 reductase. The nitroreductase activity extended to other substrates such as the related drug nilutamide and the environmental contaminants 1-nitronaphthalene and 1,3-dinitronaphthalene. Comparative experiments with cell lysates of recombinant yeast were conducted under aerobic and reduced oxygen conditions and demonstrated that the reductases are oxygen sensitive.

Prior research into the prevalence of SARS-CoV-2 infection amongst people experiencing homelessness (PEH) largely relates to people in communal forms of temporary accommodation in contexts where this type of accommodation remained a major part of the response to homelessness during the COVID-19 pandemic. Little is known about the prevalence of SARS-CoV-2 amongst PEH more broadly, and in a policy and practice context that favoured self-contained accommodation, such as Wales, UK.

Describe the prevalence of SARS-CoV-2 amongst PEH in Wales, UK, using routinely collected administrative data from the Secure Anonymised Information Linkage Databank.

Routinely collected data were used to identify PEH in Wales between 1

March 2020 and 1

March 2021. Using SARS-CoV-2 pathology testing data, prevalence rates were generated for PEH and three comparator groups (1) the not-homeless population; (2) a cohort 'exact matched’ for age, sex, local authority and area deprivation; and (3) a matched comparison group createdible for the reduced SAR-CoV-2 infection amongst PEH.

Our analysis revealed that a year into the COVID-19 pandemic, the prevalence of SARS-CoV-2 amongst PEH in Wales was lower than the general population. A policy response to homelessness that moved away from communal accommodation may be partly responsible for the reduced SAR-CoV-2 infection amongst PEH.

To combat and mitigate the transmission of the SARS-CoV-2 virus, reducing the number of social contacts within a population is highly effective. Non-pharmaceutical policy interventions, e.g. stay-at-home orders, closing schools, universities, and (non-essential) businesses, are expected to decrease pedestrian flows in public areas, leading to reduced social contacts. The extent to which such interventions show the targeted effect is often measured retrospectively by surveying behavioural changes. Approaches that use data generated through mobile phones are hindered by data confidentiality and privacy regulations and complicated by selection effects. Furthermore, access to such sensitive data is limited. However, a complex pandemic situation requires a fast evaluation of the effectiveness of the introduced interventions aiming to reduce social contacts. Location-based sensor systems installed in cities, providing objective measurements of spatial mobility in the form of pedestrian flows, are suited for such a purpose.