In semiconductor production, the technology node of a device is becoming extremely small below 5 nm. Area selective deposition (ASD) is a promising technique for creating improved overlay or self-alignment, remedying a conventional top-down method. However, the conventional materials and process (self-assembled monolayer, polymer and carbon film fabricated by chemical vapor deposition, and spin coating) for ASD are not suitable for highly conformal deposition. Thus, we investigated a new strategy to deposit conformal films in ASD by molecular layer deposition (MLD). The MLD processes were conducted for an indicone film deposited by INCA-1 (bis(trimethysily)amidodiethyl indium) and hydroquinone (HQ), as well as an alucone film deposited by TMA (trimethylaluminum) and HQ. After thermal heat treatment of the MLD films, variations in thickness, refractive index, and constituent elements of the annealed MLD films were investigated. The indicone film was used as an inhibiting layer for ASD and was etchable with a dry-etching process. The reactive ion etching process on annealed indicone film was optimized according to plasma power, gas concentration, and working pressure. Ruthenium (Ru) ALD was then performed on the annealed MLD films to investigate nucleation delaying cycles and inhibiting properties. A patterned substrate with an MLD/Si line was created via the RIE process, which was allowed to observe the selectivity of the annealed MLD films. In addition, a patterned substrate of SiO2/annealed indicone/Mo was used to investigate the Ru-selective ALD at the nanoscale. The Ru thin film was selectively deposited on the Mo side-wall surface of a 3D trench structure. The growth of the Ru film was inhibited selectively on an annealed indicone surface of approximately 5 nm.Aqueous zinc batteries are of great interest as a rechargeable energy storage system, particularly owing to the low cost and high safety of aqueous electrolytes, as well as the high capacity of zinc anodes. Unfortunately, the wide commercialization of aqueous zinc batteries is impeded by the irreversible water reduction and irregular zinc evolution issues on the anode side. Hereby, a hydrophobic and ultrathin polystyrene molecule brush layer is tethered onto the surface of zinc metal anodes to tackle the above limitations. Experimental investigations reveal that the waterproof artificial layer can sustain fast interfacial ionic transportation, minimize hydrogen evolution, and smoothen Zn deposition, thus conferring enhanced electrochemical performance to the as-protected Zn anode in both symmetric Zn//Zn cells and Zn//LiV3O8 full cells.With a view to improving the sensor lifetime, solid-contact ion-selective electrodes (ISEs) were prepared with a plasticizer-free and cross-linked poly(decyl methacrylate) matrix, to which only the ionic sites, only the ionophore, or both the ionic sites and ionophore were covalently attached. In earlier work with covalently attached ionophores or ionic sites, it was difficult to discount the presence of ionophores or ionic site impurities that were not covalently attached to the polymer backbone because the reagents used to introduce the ionophore or ionic sites had high hydrophobicities. In this work, we deliberately chose readily available hydrophilic reagents for the introduction of covalently attached H+ ionophores with tertiary amino groups and covalently attached sulfonate groups as ionic sites. This simplified the synthesis and made it possible to thoroughly remove ionophores and ionic sites not covalently attached to the polymer backbone. Our results confirm the expectation that hydrophobic ISE membranes with both covalently attached ionophores and ionic sites have impractically long response times. In contrast, ISEs with either covalently attached H+ ionophores or covalently attached ionic sites responded to pH with quick Nernstian responses and high selectivity. Both conventional plasticized poly(vinyl chloride) (PVC)-based ISEs and the new poly(decyl methacrylate) membranes were exposed to 90 °C heat for 2 h, 10% ethanol for 1 day, or undiluted blood serum for 5 days. In all three cases, the poly(decyl methacrylate) ISEs exhibited properties superior to conventional PVC-based ISEs, confirming the advantages of the covalent attachment.

Remodeling in asthma refers to structural changes in airways. The relationship between the remodeling and asthma severity remains under investigation, and data on the intensity of airway remodeling by the Global Initiative for Asthma (GINA) asthma severity classification is still scarce. Computed tomography and post-processing applications are effective tools to assess airway remodeling.

The aim of this study was to assess the severity of morphometric abnormalities of the respiratory tract in patients with various degrees of asthma severity according to GINA guidelines.

The study included 70 patients with asthma and 29 healthy volunteers corresponding to age, sex, and Body Mass Index. Patients were examined with a 128-multi-slice scanner at full inspiration. The measurements were made from the third to the ninth bronchi generations. Bronchial parameters were compared between severe asthma patients, non-severe asthma patients, and healthy volunteers.

We found no differences in the thickness of the bronchial wall, the percentage of the wall area, the inner and outer diameter, and the size of the bronchial lumen between severe and non-severe asthma groups. Significant differences were noted in the thickness of the bronchial wall and the percentage of the wall area between the severe asthma group and the healthy volunteers’ group (P value <0.017) as well as between the non-severe asthma group and the healthy volunteers’ group (P value <0.017).

Our findings indicate a similar intensity of computed tomography morphological measures of airway remodeling in all asthma severity groups as defined by GINA guidelines.

Our findings indicate a similar intensity of computed tomography morphological measures of airway remodeling in all asthma severity groups as defined by GINA guidelines.Studies have confirmed the involvement of androgens in bird erythropoiesis, suggesting its potential function as a mediator thereof. However, little is known on whether anti-androgenic treatment reduces erythropoiesis and whether changes in endogenous androgen levels are reflected in red blood cell (RBC) indices in birds. Clarifying such issues would highlight the importance of androgens in mediating avian erythropoiesis and bring attention to the effects of endocrine-disrupting chemicals with anti-androgenic activity on their ecology. The present study focused on hematocrit levels among the RBC indices, as well as the relationship between androgens and hematocrit levels in the Japanese quail (Coturnix japonica). In experiment 1, daily injections (i.m.) of testosterone propionate administered to immature quails for a week dose-dependently increased their hematocrit levels. In experiment 2, daily injections (i.m.) of flutamide, a general antagonist of the androgen receptor (AR), administered to adult male quails for a week dose-dependently decreased their hematocrit levels. In experiment 3, weekly blood collection from male quails through the immature to mature stages revealed that changes in endogenous testosterone concentrations were correlated with changes in hematocrit levels along with sexual maturation. The aforementioned results suggested that androgen stimulates erythropoiesis via the ARs and further highlighted the biological importance of androgens on erythropoiesis in quails. Moreover, given that hematocrit is considered a key determinant of aerobic performance related to migration in birds, these findings highlight the need for investigating the effects of anti-androgenic chemicals on the hematology of migratory species for their conservation.

Evaluate for differences in demographic and clinical characteristics and subjective and objective measures of cognitive function (CF) between younger older adults (YOA, 60-69years) and older adults (OA, ≥70years).

Cross-sectional.

Older oncology patients (n=139) completed subjective (Attentional Function Index, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) CF scale) and objective (Montreal Cognitive Assessment, Trail Making Test (TMT) A & B) measures of CF prior to chemotherapy. Data were analyzed using parametric and nonparametric tests.

No differences were found between the two groups for any of the subjective or objective CF measures, except that OA patients had higher TMT B scores. Compared with the general population, OAs had significantly higher EORTC CF scores and YOAs had significantly worse scores for all of the objective tests. Clinically meaningful difference between group differences was found for the TMT B test.

No differences were found between the two groups for any of the subjective or objective CF measures, except that OA patients had higher TMT B scores. Compared with the general population, OAs had significantly higher EORTC CF scores and YOAs had significantly worse scores for all of the objective tests. Clinically meaningful difference between group differences was found for the TMT B test.

Frailty is a syndrome characterized by reduced physiologic reserve and increased vulnerability to poor health outcomes. Disruption of sensorineural function appears to serve as a novel biomarker of frailty. Using population-level data, we sought to characterize the association between otolaryngic sensory dysfunction and frailty.

A cross-sectional analysis of the 2011-2012 US National Health and Nutrition Examination Survey was performed on adults ≥40 years of age (n=2138). Participants were grouped by subjective gustatory dysfunction (sGD), olfactory dysfunction (sOD), hearing loss (sHL), and measured hearing loss (mHL) with pure tone averages (PTAs). Frailty was operationalized using a continuous 36-item frailty index (FI) scored from 0 to 1, stratified in 4 categories („non-frail,” „vulnerable,” „frail,” or „most frail”).

All sensory loss groups had significantly higher FI scores than those without sensory loss (sGD = 0.15; sOD = 0.14; sHL = 0.15; low-frequency mHL = 0.16; high-frequency mHL = 0.14vs viduals with modifiable risk factors.

Social rank has a profound influence on the behavior and health of humans and animals.

To explore the effect of a combination of living Bifidobacterium, Lactobacillus and Streptococcus (CLB) on anxiety- and depression-like behaviors and social rank, mice were subjected to a social dominance tube test (SDTT). The behaviors, rank, gut microbiota, and expression of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured.

The results indicated that CLB improved the SDTT ranking score of the losers and alleviated anxiety-like behaviors of the winners. CLB decreased the level of Desulfovibrio and augmented the level of Mollicutes in the feces, increased BDNF content, and reduced the level of tumor necrosis factor-α in the hippocampus.

These findings indicated that CLB may be used for the treatment of anxiety and improvement of the rank score via regulation of gut microbiota and anti-inflammatory effects.

These findings indicated that CLB may be used for the treatment of anxiety and improvement of the rank score via regulation of gut microbiota and anti-inflammatory effects.Data tables for machine learning and structure-activity relationship modelling (QSAR) are often naturally organized in blocks of data, where multiple molecular representations or sets of descriptors form the blocks. Multi-block Orthogonal Component Analysis (MOCA), a new analytical tool, can be used to explore such data structures in a single model, identifying principal components that are unique to a single block or joint over multiple blocks. We applied MOCA to two sets of 550 and 300 molecules and up to 9213 molecular descriptors organized in 11 blocks. The MOCA models reveal relationships between the blocks and overarching trends across the whole dataset. Based on the MOCA joint components, we propose a quantitative metric for the redundancy of blocks, useful for a priori block-wise feature selection or evaluation of new molecular representations. The second data set includes 7 ecotoxicological study endpoints for crop protection chemicals, for which we (re-)discovered some general trends and linked them to molecular properties. Using a single MOCA model we estimated the predictive potential of each block and the model-ability of the target block.Turbo Similarity Searching (TSS) is the simplest and most recent chemical similarity searching (SS) approach, which improves the effectiveness of SS by performing a multi-target searching. TSS has four important elements, namely structural representation, similarity coefficient, number of nearest neighbours (NNs), and fusion rule, and any changes in these elements could affect the TSS results. A previous study suggested the advantage of using large numbers of reference compounds with small fractions of the database structures to obtain a better recall in group fusion. Therefore, this study aims to investigate the effect of partial ranking on TSS utilising different fusion rules and different numbers of NNs on the ChEMBL database and to evaluate whether these observations hold in TSS. Furthermore, the objective is to observe the effect of the indirect relationship feature of TSS on the partial ranking investigation. The results showed that the effect of using partial ranking on TSS was significant. This study also found that the performance of TSS improved as the database proportions used in the fusion process decreased and by using a small number of NNs. In addition, fusion rules based on reciprocal rank positions (RKP), maximum similarity score (sMAX), and sMNZ were superior to all the other fusion rules.Composites based on carbon nanotubes (CNTs) are promising patternable materials that can be engineered to incorporate the outstanding properties of CNTs into various applications via printing technologies. However, conventional printing methods for CNTs require further improvement to overcome the major drawbacks that limit the patterning resolution and target substrate. Herein, an intaglio contact printing method based on a CNT/paraffin composite is presented for realizing highly precise CNT network patterns without restrictions on the substrate. In this method, the CNT/paraffin composite can be patterned with a high resolution ( less then 10 µm) and neatly transferred onto various substrates with a wide range of surface energies, including human skin. The patterned composite exhibits high durability against structural deformations, and structural damage caused by fatigue accumulation can be cured in a few seconds. In addition, miniaturized sensing and energy-harvesting applications are demonstrated with high performances. The present method facilitates the rapid fabrication of highly precise interdigitated electrodes via one-step printing, enabling high-performance operation and miniaturization of the devices. It is anticipated that these results will not only spur the further development of various applications of CNTs but also contribute to advances in soft lithography methods applicable to many fields of science and engineering.

To test the feasibility of a new device for gasless laparoscopy in providing working space for diaphragmatic hernia repair in an ex vivo canine model as a pre-clinical study.

Technical feasibility study.

Eight beagles and two greyhound cadavers (not client-owned).

The new device was used for abdominal traction in gasless laparoscopic reconstruction of diaphragmatic hernias produced in dog cadavers. It consists of three main parts (vertical and horizontal rods, a three-piece structure, and a 3D-printed unit that incorporates slots for haemostatic forceps). Composite hernias (two incisions of about 4cm) were closed by an intra-corporeal suture [suture group (GS), n=5] or by a central suture and a polypropylene mesh [mesh group (GM), n=5]. Surgical steps were T1 (primary port access up to third port placement), T2 (defect development), and T3 (diaphragmatic reconstruction). Total surgical time (TT) was also recorded.

The defect was successfully developed and reconstructed in all cadavers. To close the defect, 7.0 ± 0.7 crossed mattress sutures were required in the GS, and 15.2 ± 1.9 hernia staples and one intra-corporal suture were used in the GM. T3 was longer (p=0.0076) in GS (50.00 ± 16.46min) than in GM (23.24 ± 5.25min). TT was 87.22 ± 19.23min in GS and 66.45 ± 6.38min in GM (p=0.0547).

Gasless laparoscopic diaphragmatic hernia repair using the developed device is feasible in the canine cadaver model. Both suture and mesh graft techniques for experimental diaphragmatic herniorrhaphy can be performed using this new device in this pre-clinical model.

This new device for gasless laparoscopy allows diaphragmatic herniorrhaphy by intra-corporeal suture or mesh implantation in ex vivo canine model. The device demonstrates potential for future use in clinical cases.

This new device for gasless laparoscopy allows diaphragmatic herniorrhaphy by intra-corporeal suture or mesh implantation in ex vivo canine model. The device demonstrates potential for future use in clinical cases.To explore the effect and magnitude of effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on haematocrit and haemoglobin and the related cardiorenal benefits in patients with type 2 diabetes mellitus (T2DM), PubMed, Web of Science, CENTRAL and EMBASE were searched to identify eligible trials. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Seventy-eight studies were included in the meta-analysis. SGLT2 inhibitors significantly increased haematocrit and haemoglobin levels compared with control (total WMD 2.27% [95% CI 2.08, 2.47] and 6.20 g/L [95% CI 5.68, 6.73], respectively). Except for dapagliflozin (p = 0.000), no notable dose-dependent relationship was revealed for other SGLT2 inhibitors. The effect could be sustained or even slightly increased with long-term therapy (coef. =0.009, 95% CI [0.005, 0.013], p = 0.000). In subgroup analyses, haematocrit elevation increased with higher body mass index (BMI). A greater haematocrit elevation could be observed in white patients or when compared with active controls. In conclusion, SGLT2 inhibitors increased haematocrit and haemoglobin levels in T2DM patients. Changes in haematocrit and haemoglobin seem to be surrogate markers of improvement in renal metabolic stress, and important mediators involved in cardiorenal protection.The „Hodgkin-like” lymphomas including classic Hodgkin lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, T cell/histiocyte rich large B cell lymphoma, and primary mediastinal large B cell lymphoma have been shown to be pathobiologically related. With the exception of primary mediastinal large B cell lymphoma, these lymphomas have similar morphologic growth patterns with occasional neoplastic cells within a prominent reactive cell background. Historically, distinguishing these entities was difficult by flow cytometry; however, over the past 15 years, our laboratory has developed antibody-fluorochrome combinations capable of accurately distinguishing these entities by their immunoprofile. Additionally, an algorithmic approach based on characterization of the background reactive B-cell and T-cell populations can aid in narrowing the differential diagnosis. This review summarizes both the morphologic and immunophenotypic features and the current flow cytometric insights of the neoplastic and reactive populations found in this unique subset of lymphomas.In recent years, to overcome the problem of low tissue penetration power of light in photodynamic therapy (PDT), sonodynamic therapy (SDT) with ultrasound (US) as the drug stimulus has emerged as a potential alternative to PDT. The significantly higher tissue penetration capacity of US is reported to allow the treatment of deep-seated tumours. In general, organic molecules and nanomaterials dominate as the sonosensitizers in this area of research, and the potential of metal complexes in SDT is not yet well explored. In this highlight, we have summarized two recent literature reports in which researchers have explored the efficiency of metal complexes as sonosensitizers for the first time. These reports indicate the high potential of metal complexes in SDT.Primary pulmonary meningioma (PPM) is a very rare and mostly benign disease. Although PPM is incidentally detected as a solitary pulmonary nodule on X-ray or chest computed tomography, it does not have unique radiological characteristics; thus, it is difficult to differentiate it from other lung tumors. A healthy 54-year-old man visited our hospital because of multiple variable-sized lung nodules. He had no contributive medical history and no abnormality that was suggestive of extrapulmonary malignancy. Video-assisted thoracoscopic wedge resection was undertaken for diagnosis, and the tumor cells were histopathologically confirmed as PPM. Brain magnetic resonance imaging revealed no intracranial tumor. The patient has been well and without any progression of the remaining lesions over 24 months. Here, we present the clinicopathological features of this case in which the patient’s nodules were mistaken for multiple metastatic lung nodules.A chance encounter in 1975 with David Crews in Harvard Square led to 3 years of research in his lab, investigating the role of testosterone (T) in male sexual behavior of the lizard, Anolis carolinensis. In 1988 when I began my practice as a urologist and specialist in men’s health, my research experience with lizards led me to offer testosterone therapy (TTh) to men suffering with symptoms of testosterone deficiency, despite the universal belief that TTh caused prostate cancer (PCa). My investigation of this topic over 30+ years has led to revolutionary changes in the diagnosis and treatment of men with testosterone deficiency and our understanding of the biology of testosterone and PCa. Today, it is routine for men successfully treated for PCa to receive TTh, a remarkable fact given that standard treatment for men with advanced PCa has been androgen deprivation for the last 80 years. Our research showed low T was not protective for PCa; TTh did not appear to worsen PCa for various cancer stages; and provided the theoretical framework for understanding why androgen deprivation shrinks PCa tumors, yet TTh appears to not cause PCa growth under most conditions. This is based on the Saturation Model, which recognizes there is a finite ability of androgens to stimulate PCa growth, which becomes maximal at low T concentrations. David Crews was an outstanding mentor-the lessons I learned from him inspired a lifetime of work, which in turn led to improved quality of life for millions of men.

Staphylococcus aureus cause diseases both in humans and animals. These diseases range from mild to fatal infections thus necessitating development of a specific molecular method for detection of pathogenic S. aureus.

To identify and analyze genetic profile of pathogenic S. aureus using bacteriophage based genetic biomarkers.

Using culture and biochemical methods, 148 S. aureus (87 %) were isolated from 170 raw milk samples taken from 10 dairy farms in Marsabit and Isiolo counties in Northern Kenya between June 2016 and February 2017. The samples were collected directly from dairy lactating cows previously diagnosed with S. aureus in a follow-up study. The isolates were analyzed by PCR and sequencing of beta hemolysin (hlb) gene. The genetic relationship between five Kenyan S. aureus isolates and five isolates previously identified was inferred.

From the 96 isolates screened for hlb gene, 75 (78.1%) tested positive. Some of the positive isolates yielded a band size of 975bp, while others 1100bp. Through Basic Local Alignment Search Tool (BLAST) search analysis, the two different band sizes (975bp and 1100bp) were both confirmed to be hlb gene from S. aureus isolates indicating that the difference in band size may have been due to deletions that were detected in the 975bp hlb gene. Some S. aureus isolates from Kenya appeared to be closely related to isolates from other parts of the world, while some showed a distant relationship.

Phage-derived hlb gene is a suitable molecular marker for detection of pathogenic S. aureus.

Phage-derived hlb gene is a suitable molecular marker for detection of pathogenic S. aureus.

Arterial spin labeling (ASL) is a functional neuroimaging technique that has been frequently used to investigate acute pain states. A major advantage of ASL as opposed to blood-oxygen-level-dependent functional neuroimaging is its applicability for low-frequency designs. As such, ASL represents an interesting option for studies in which repeating an experimental event would reduce its ecological validity. Whereas most ASL pain studies so far have used thermal stimuli, to our knowledge, no ASL study so far has investigated pain responses to sharp mechanical pain.

As a proof of concept, we investigated whether ASL has the sensitivity to detect brain activation within core areas of the nociceptive network in healthy controls following a single stimulation block based on 96 s of mechanical painful stimulation using a blunt blade.

We found significant increases in perfusion across many regions of the nociceptive network such as primary and secondary somatosensory cortices, premotor cortex, posterior insula, ted to investigate acute pain in a single event paradigm, although to detect activation within some regions of the nociceptive network, the sensitivity of our paradigm seemed to be limited. Regarding the posterior insula, our paradigm was sensitive enough to detect a correlation between pain intensity ratings and pain-induced perfusion increase. Previous experimental pain studies have proposed that intensity coding in this region may be restricted to thermal stimulation. Our result demonstrates that the posterior insula encodes intensity information for mechanical stimuli as well.Given the worldwide increasing prevalence of severe obesity and considering the amount of scientific evidence demonstrating the beneficial effects of bariatric surgery (BS), it is surprising that only a fraction of patients with obesity undergo BS. We therefore conducted an anonymized online survey among individuals with a history of BS to understand factors influencing the deciding process leading to BS. Respondents were recruited on a voluntary basis from obesity-related social media groups between April and June 2020. The self-designed, non-validated questionnaire consisted of 20 questions and was open to any participants with a history of BS. Of 851 participants who started the survey, 665 completed the questionnaire (completion rate of 78.1%). Five years after BS, still 70% of the survey-participants were very satisfied or satisfied with the surgical result. However, the majority (73.3%) would have undergone BS earlier. The main motivation to choose BS was related to health status or quality of life. Important characteristics for a bariatric surgeon to obtain patients’ trust are „taking time and listen” (74.7%), empathy (64%) and sympathy (56%). Post-operative satisfaction with the surgical outcome was high and long-lasting in this large cohort of BS patients. However, most participants would retrospectively have undergone BS earlier. The main reason to choose BS as treatment for their obesity were impaired physical health or reduced quality of life. Nearby location to patients’ residence and availability of surgeons with empathy were decisive motives for bariatric centre selection.The English grain aphid, Sitobion avenae, is a major agricultural pest of wheat, barley and oats, and one of the principal vectors of Barley Yellow Dwarf Virus (BYDV) leading to significant reductions in grain yield, annually. Emerging resistance to and increasing regulation of insecticides has resulted in limited options for their control. Using PacBio HiFi data, we have produced a high quality draft assembly of the S. avenae genome; generating a primary assembly with a total assembly size of 475.7 Mb, and an alternate assembly with a total assembly size of 430.8 Mb. Our primary assembly was highly contiguous with only 326 contigs and a contig N50 of 15.95 Mb. Assembly completeness was estimated at 97.7% using BUSCO analysis and 31,007 and 29,037 protein coding genes were predicted from the primary and alternate assemblies, respectively. This assembly, which is to our knowledge the first for an insecticide resistant clonal lineage of English grain aphid, will provide novel insight into the molecular and mechanistic determinants of resistance and will facilitate future research into mechanisms of viral transmission and aphid behavior.Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (226, DHA)-containing phospholipids (DHA-PLs) in physiology. Here, we investigated the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) triggered by RhoA inhibition-associated cell spreading. Lipidomic analyses showed that human umbilical vein endothelial cells (HUVECs) subjected to a DHA diet undergo a 6-fold enrichment in DHA-PLs at the plasma membrane (PM) at the expense of monounsaturated oleic acid-containing PLs (OA-PLs). Consequently, DHA-PL enrichment at the PM induces a reduction in cell thickness and shifts cellular membranes towards a permissive mode of membrane fusion for transcellular tunnel initiation. We provide evidence that a global homeostatic control of membrane tension and cell cortex rigidity minimizes overall changes of TEM area through a decrease of TEM size and lifetime. Conversely, low DHA-PL levels at the PM lead to the opening of unstable and wider TEMs. Together, this provides evidence that variations of DHA-PL levels in membranes affect cell biomechanical properties.Tricuspid regurgitation (TR) is a highly prevalent condition and an independent risk factor for adverse outcomes. Multiple clinical guidelines exist for the diagnosis and management of TR, but the recommendations may sometimes vary. We systematically reviewed high-quality guidelines with a specific focus on areas of agreement, disagreement and gaps in evidence. We searched MEDLINE and EMBASE (01/01/2011 – 30/08/2021), the Guidelines International Network International, Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, Google Scholar and websites of relevant organizations for contemporary guidelines that were rigorously developed (as assessed by the Appraisal of Guidelines for Research and Evaluation II tool). Three guidelines were finally retained. There was consensus on a TR grading system, recognition of isolated functional TR associated with atrial fibrillation, and indications for valve surgery in symptomatic vs asymptomatic patients, primary vs secondary, and isolated TR forms. Discrepancies exist on the role of biomarkers, complementary multi-modality imaging, exercise echocardiography and cardiopulmonary exercise testing for risk stratification and clinical decision-making of progressive TR and asymptomatic severe TR, management of atrial functional TR and choice of transcatheter tricuspid valve intervention (TTVI). Risk-based thresholds for quantitative TR grading, robust risk score models for TR surgery, surveillance intervals, population-based screening programmes, TTVI indications and consensus on endpoint definitions are lacking.When intracellular, pathogenic Salmonella reside in a membrane compartment composed of interconnected vacuoles and tubules, the formation of which depends on the translocation of bacterial effectors into the host cell. Cytoskeletons and their molecular motors are prime targets for these effectors. In this study, we show that the microtubule molecular motor KIF1Bβ (a splice variant of KIF1B), a member of the kinesin-3 family, is a key element for the establishment of the Salmonella replication niche as its absence is detrimental to the stability of bacterial vacuoles and the formation of associated tubules. Kinesin-3 interacts with the Salmonella effector SifA but also with SKIP (also known as PLEKHM2), a host protein complexed to SifA. The interaction with SifA is essential for the recruitment of kinesin-3 on Salmonella vacuoles whereas that with SKIP is incidental. In the non-infectious context, however, the interaction with SKIP is essential for the recruitment and activity of kinesin-3 only on a fraction of the lysosomes. Finally, our results show that, in infected cells, the presence of SifA establishes a kinesin-1 and kinesin-3 recruitment pathway that is analogous to and functions independently of that mediated by the Arl8a and Arl8b GTPases. This article has an associated First Person interview with the first author of the paper.An important and often overlooked subpopulation of cancer survivors is individuals who are diagnosed with or progress to advanced or metastatic cancer. Living longer with advanced or metastatic cancer often comes with a cost of burdensome physical and psychosocial symptoms and complex care needs, however research is limited on this population. Thus, in May 2021, the National Cancer Institute convened subject matter experts, researchers, clinicians, survivors, and advocates a for a 2-day virtual meeting. The purpose of this report is to provide a summary of the evidence gaps identified by subject matter experts and attendees and key opportunities identified by NCI in five research areas epidemiology and surveillance, symptom management, psychosocial research, healthcare delivery, and health behaviors. Identified gaps and opportunities include the need to develop new strategies to estimate the number of individuals living with advanced and metastatic cancers, understand and address emerging symptom trajectories, improve prognostic understanding and communication between providers, patients, and caregivers, develop and test models of comprehensive survivorship care tailored to these populations, and assess patient and provider preferences for health behavior discussions throughout the survivorship trajectory. To best address the needs of individuals living with advanced and metastatic cancer and to deliver comprehensive evidence-based quality care, research is urgently needed to fill evidence gaps, and it is essential to incorporate the survivor perspective. Developing such an evidence base is critical to inform policy and practice.

Bone remodelling can be followed through the bone turnover markers (BTMs). Aim of the present study was to record the fluctuation of an osteoclastic and an osteoblastic BTM [C-terminal telopeptide of type I collagen (CTX) and N-terminal pro-peptide of type I pro-collagen (PINP), respectively] in both the gingival crevicular fluid (GCF) and the serum of orthodontic patients before and after the initial application of orthodontic forces.

Twenty-one Caucasian patients were prospectively evaluated. GCF and blood samples were collected in order to measure the selected biomarkers by ELISA at three time-points exactly before, 5 days, and 14 days after bonding of the appliances. Standardized sample handling and patient preparation procedures were adopted in order to reduce pre-analytical variability.

GCF and serum CTX levels were found to be independent of age, although higher in the serum of female subjects. PINP levels were found higher in the serum of patients ≥25 years old, as well as in the GCF of males. A positive correlation between serum and GCF baseline PINP levels was observed.

The effect of orthodontic treatment on bone remodelling might not be absolutely representative of the local bone microenvironment as the levels of the specific BTMs where measured within the GCF of the lower front teeth.

This is the first time PINP and CTX have been evaluated in the GCF and serum of orthodontic patients with fixed appliances. No statistically significant alterations of CTX and PINP levels in the GCF and the serum of patients were recorded over time during the initial stages of orthodontic treatment.

This is the first time PINP and CTX have been evaluated in the GCF and serum of orthodontic patients with fixed appliances. No statistically significant alterations of CTX and PINP levels in the GCF and the serum of patients were recorded over time during the initial stages of orthodontic treatment.Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.

Constraint-based reconstruction and analysis (COBRA) is a widely used modeling framework for analyzing and designing metabolic networks. Here we present CNApy, an open source cross-platform desktop application written in Python, which offers a state-of-the-art graphical front-end for the intuitive analysis of metabolic networks with COBRA methods. While the basic look-and-feel of CNApy is similar to the user interface of the MATLAB toolbox CellNetAnalyzer (CNA), it provides various enhanced features by using components of the powerful Qt library. CNApy supports a number of standard and advanced COBRA techniques and further functionalities can be easily embedded in its GUI facilitating modular extension in the future.

CNApy can be installed via conda and its source code is freely available at https//github.com/cnapy-org/CNApy under the Apache 2 license.

CNApy can be installed via conda and its source code is freely available at https//github.com/cnapy-org/CNApy under the Apache 2 license.The invasive avian vampire fly (Philornis downsi, Diptera Muscidae) is considered one of the greatest threats to the endemic avifauna of the Galápagos Islands. The fly larvae parasitize nearly every passerine species, including Darwin’s finches. Most P. downsi research to date has focused on the effects of the fly on avian host fitness and mitigation methods. A lag in research related to the genetics of this invasion demonstrates, in part, the need to develop full-scale genomic resources with which to address further questions within this system. In this study, an adult female P. downsi was sequenced to generate a high-quality genome assembly. We examined various features of the genome (e.g., coding regions and noncoding transposable elements) and carried out comparative genomics analysis against other dipteran genomes. We identified lists of gene families that are significantly expanding or contracting in P. downsi that are related to insecticide resistance, detoxification, and counter defense against host immune responses. The P. downsi genome assembly provides an important resource for studying the molecular basis of successful invasion in the Galápagos and the dynamics of its population across multiple islands. The findings of significantly changing gene families associated with insecticide resistance and immune responses highlight the need for further investigations into the role of different gene families in aiding the fly’s successful invasion. Furthermore, this genomic resource provides a necessary tool to better inform future research studies and mitigation strategies aimed at minimizing the fly’s impact on Galápagos birds.

Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease (CAD). This study evaluated the effects of revascularization on CFC as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging.

A total of 314 patients with stable CAD underwent [15O]H2O PET imaging at baseline and after myocardial revascularization to assess changes in hMBF, CFR, and CFC in 415 revascularized vessels. Using thresholds for ischaemia and normal perfusion, vessels were stratified in five CFC categories myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC, and normal flow. Additionally, the association between CFC increase and the composite endpoint of death and non-fatal myocardial infarction (MI) was studied. Vessel-specific CFC improved after revascularization (P < 0.01). Furthermore, baseline CFC was an independent predictor of CFC increase (P < 0.01). The largest changes in ΔhMBF (0.90 ± 0.74, 0.93 ± 0.65, 0.79 ± 0.74, 0.48 ± 0.61, and 0.29 ± 0.66 mL/min/g) and ΔCFR (1.01 ± 0.88, 0.99 ± 0.69, 0.87 ± 0.88, 0.66 ± 0.91, and -0.01 ± 1.06) were observed in vessels with lower baseline CFC (P < 0.01 for both). During a median follow-up of 3.5 (95% CI 3.1-3.9) years, an increase in CFC was independently associated with lower rates of death and non-fatal MI (HR 0.43, 95% CI 0.19-0.98, P = 0.04).

Successful revascularization results in an increase in CFC. Furthermore, baseline CFC was an independent predictor of change in hMBF, CFR, and subsequently CFC. In addition, an increase in CFC was associated with a favourable outcome in terms of death and non-fatal MI.

Successful revascularization results in an increase in CFC. Furthermore, baseline CFC was an independent predictor of change in hMBF, CFR, and subsequently CFC. In addition, an increase in CFC was associated with a favourable outcome in terms of death and non-fatal MI.The canonical Wnt/β-catenin pathway governs a multitude of developmental processes in various cell lineages, including the melanocyte lineage. Indeed, β-catenin regulates transcription of Mitf-M, the master regulator of this lineage. The first wave of melanocytes to colonize the skin is directly derived from neural crest cells, whereas the second wave of melanocytes is derived from Schwann cell precursors (SCPs). We investigated the influence of β-catenin in the development of melanocytes of the first and second waves by generating mice expressing a constitutively active form of β-catenin in cells expressing tyrosinase. Constitutive activation of β-catenin did not affect the development of truncal melanoblasts but led to marked hyperpigmentation of the paws. By activating β-catenin at various stages of development (E8.5-E11.5), we showed that the activation of β-catenin in bipotent SCPs favored melanoblast specification at the expense of Schwann cells in the limbs within a specific temporal window. Furthermore, in vitro hyperactivation of the Wnt/β-catenin pathway, which is required for melanocyte development, induces activation of Mitf-M, in turn repressing FoxD3 expression. In conclusion, β-catenin overexpression promotes SCP cell fate decisions towards the melanocyte lineage.Despite playing a critical role in evolutionary processes and outcomes, relatively little is known about rates of recombination in the vast majority of species, including squamate reptiles-the second largest order of extant vertebrates, many species of which serve as important model organisms in evolutionary and ecological studies. This paucity of data has resulted in limited resolution on questions related to the causes and consequences of rate variation between species and populations, the determinants of within-genome rate variation, as well as the general tempo of recombination rate evolution on this branch of the tree of life. In order to address these questions, it is thus necessary to begin broadening our phylogenetic sampling. We here provide the first fine-scale recombination maps for two species of spiny lizards, Sceloporus jarrovii and Sceloporus megalepidurus, which diverged at least 12 Mya. As might be expected from similarities in karyotype, population-scaled recombination landscapes are largely conserved on the broad-scale. At the same time, considerable variation exists at the fine-scale, highlighting the importance of incorporating species-specific recombination maps in future population genomic studies.

Minimally invasive mitral valve surgery (MIMVS) has been performed increasingly for the past 2 decades; however, large comparative studies on short- and long-term outcomes have been lacking. This study aims to compare short- and long-term outcomes of patients undergoing MIMVS versus median sternotomy (MST) based on real-world data, extracted from the Netherlands Heart Registration.

Patients undergoing mitral valve surgery, with or without tricuspid valve, atrial septal closure and/or rhythm surgery between 2013 and 2018 were included. Primary outcomes were short-term morbidity and mortality and long-term survival. Propensity score matching analyses were performed.

In total, 2501 patients were included, 1776 were operated through MST and 725 using an MIMVS approach. After propensity matching, no significant differences in baseline characteristics persisted. There were no between-group differences in 30-day mortality (1.1% vs 0.7%, P = 0.58), 1-year mortality (2.6% vs 2.1%, P = 0.60) or perioperative stroke rate (1.1% vs 0.6%, P = 0.25) between MST and MIMVS, respectively. An increased rate of postoperative arrhythmia was observed in the MST group (31.3% vs 22.4%, P < 0.001). A higher repair rate was found in the MST group (80.9% vs 76.3%, P = 0.04). No difference in 5-year survival was found between the matched groups (95.0% vs 94.3%, P = 0.49). Freedom from mitral reintervention was 97.9% for MST and 96.8% in the MIMVS group (P = 0.01), without a difference in reintervention-free survival (P = 0.30).

The MIMVS approach is as safe as the sternotomy approach for the surgical treatment of mitral valve disease. However, it comes at a cost of a reduced repair rate and more reinterventions in the long term, in the real-world.

The MIMVS approach is as safe as the sternotomy approach for the surgical treatment of mitral valve disease. However, it comes at a cost of a reduced repair rate and more reinterventions in the long term, in the real-world.The structure of the microbial community during sand crab juice fermentation was analyzed using culture-based methods and high-throughput 16S rRNA gene sequencing. Additionally, the changes in amino acid nitrogen (AAN) and total volatile basic nitrogen (TVB-N) were evaluated. Staphylococcus equorum, Staphylococcus arlettae, Staphylococcus saprophyticus, Salinicoccus amylolyticus and Bacillus cereus were isolated by traditional culture isolation technique. The Good’s coverage obtained by high-throughput sequencing was over 99.5%, and the Chao1 and Simpson indices showed small fluctuations, indicating that the species abundance and diversity did not change significantly during the fermentation process, although the abundance decreased. Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria were the dominant bacterial phyla observed during fermentation, whereas Aquabacterium, Roseovarius, Muribaculaceae, and Silicimonas were the dominant bacterial genera. The AAN content increased from 0.15 to 0.43 g/100 mL during the 15-day fermentation, indicating the production of small peptides and amino acids during fermentation. The TVB-N content (25.2 mg/100 mL) on day 15 indicated slight spoilage of sand crab juice, although the freshness conformed to the production standard. These results provide a theoretical basis for improving the quality and optimizing the production process of sand crab juice.Gamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation is incompletely understood. Set2, which deposits H3K36me3 modifications, is required for GSC differentiation during Drosophila oogenesis. We discovered that the H3K36me3 reader Male-specific lethal 3 (Msl3) and histone acetyltransferase complex Ada2a-containing (ATAC) cooperate with Set2 to regulate GSC differentiation in female Drosophila. Msl3, acting independently of the rest of the male-specific lethal complex, promotes transcription of genes, including a germline-enriched ribosomal protein S19 paralog RpS19b. RpS19b upregulation is required for translation of RNA-binding Fox protein 1 (Rbfox1), a known meiotic cell cycle entry factor. Thus, Msl3 regulates GSC differentiation by modulating translation of a key factor that promotes transition to an oocyte fate.Expansion of interstitial cells in the adult kidney is a hallmark of chronic disease, whereas their proliferation during fetal development is necessary for organ formation. An intriguing difference between adult and neonatal kidneys is that the neonatal kidney has the capacity to control interstitial cell proliferation when the target number has been reached. In this study, we define the consequences of inactivating the TGFβ/Smad response in the mouse interstitial cell lineage. We find that pathway inactivation through loss of Smad4 leads to overproliferation of interstitial cells regionally in the kidney medulla. Analysis of markers for BMP and TGFβ pathway activation reveals that loss of Smad4 primarily reduces TGFβ signaling in the interstitium. Whereas TGFβ signaling is reduced in these cells, marker analysis shows that Wnt/β-catenin signaling is increased. Our analysis supports a model in which Wnt/β-catenin-mediated proliferation is attenuated by TGFβ/Smad to ensure that proliferation ceases when the target number of interstitial cells has been reached in the neonatal medulla.Transcriptome analyses performed in both human and zebrafish indicate strong expression of Apoe and Apoc1 by microglia. Apoe expression by microglia is well appreciated, but Apoc1 expression has not been well-examined. PPAR/RXR and LXR/RXR receptors appear to regulate expression of the apolipoprotein gene cluster in macrophages, but a similar role in microglia in vivo has not been studied. Here, we characterized microglial expression of apoc1 in the zebrafish central nervous system (CNS) in situ and demonstrate that in the CNS, apoc1 expression is unique to microglia. We then examined the effects of PPAR/RXR and LXR/RXR modulation on microglial expression of apoc1 and apoeb during early CNS development using a pharmacological approach. Changes in apoc1 and apoeb transcripts in response to pharmacological modulation were quantified by RT-qPCR in whole heads, and in individual microglia using hybridization chain reaction (HCR) in situ hybridization. We found that expression of apoc1 and apoeb by microglia were differentially regulated by LXR/RXR and PPAR/RXR modulating compounds, respectively, during development.