Head and neck cancer (HNC) is the sixth leading cause of cancer death worldwide. Due to the low early diagnosis rate of HNC, local recurrence and high distant metastasis rate are the main reasons for treatment failure. Therefore, it is important to establish a method of diagnosis and monitoring, which is convenient, safe, reproducible, sensitive and specific. Compared with tissue biopsy, liquid biopsy is an emerging biopsy technique, which has the advantages of re-sampling, noninvasive and cost-effectiveness, and has shown good diagnostic and prognostic value in studies for various types of malignant solid tumors. This review introduces liquid biopsy, its research progress and prospects in HNC including early diagnosis, staging, grading, prognosis assessment and disease surveillance.Efforts to impart responsiveness to environmental stimuli in artificial hydrogel fibers are crucial to intelligent, shape-memory electronics and weavable soft robots. However, owing to the vulnerable mechanical property, poor processability, and the dearth of scalable assembly protocols, such functional hydrogel fibers are still far from practical usage. Herein, we demonstrate an approach toward the continuous fabrication of an electro-responsive hydrogel fiber by using the self-lubricated spinning (SLS) strategy. The polyelectrolyte inside the hydrogel fiber endows it with a fast electro-response property. After solvent exchange with triethylene glycol (TEG), the maximum tensile strength of the hydrogel fiber increases from 114 kPa to 5.6 MPa, far superior to those hydrogel fiber-based actuators reported previously. Consequently, the flexible and mechanical stable hydrogel fiber is knitted into various complex geometries on demand such as a crochet flower, triple knot, thread tube, pentagram, and hollow cage. Additionally, the electrochemical-responsive ionic hydrogel fiber is capable of acting as soft robots underwater to mimic biological motions, such as Mobula-like flapping, jellyfish-mimicking grabbing, sea worm-mimicking multi-degree of freedom movements, and human finger-like smart gesturing. This work not only demonstrates an example for the large-scale production of previous infeasible hydrogel fibers, but also provides a solution for the rational design and fabrication of hydrogel woven intelligent devices.There is no doubt that electric fields of a specific frequency and intensity could excite certain vibrational modes of a macromolecule, which alters its mode coupling and conformation. Motivated by recent experiments and theories, we study the mode coupling between the Fe-CO mode and CO-stretch mode and vibration energy transfer among the active site and proteins in carboxyhemoglobin (HbCO) under different electric fields using the quasi-static two-dimensional infrared spectra. This study uses iron-porphyrin-imidazole-CO and two distal histidines in HbCO as the subsystem. The potential energy and dipole moment surfaces of the subsystem are calculated using an all-electron ab initio (B3LYP-D3(BJ)) method with the basis set Lanl2dz for the Fe atom and 6-31G(d,p) for C, H, O, and N atoms. Although the subsystem is reduced dimensionally, the anharmonic frequency and anharmonicity of the CO-stretch mode show excellent agreement with experimental values. We use the revealing noncovalent interaction method to confirm the hydrogen bond between the Hε atom of the His63 and the CO molecule. Our study confirms that the mode coupling between the Fe-CO mode and CO-stretch mode does not exist when the subsystem is free of electric field perturbation, which is coupled when the electric field is -0.5142 V/nm. In addition, with the increases of distance between the active site and the His92, there is no vibrational energy transfer between them when the electric field is 1.028 V/nm. We believe that our work could provide new ideas for increasing the dissociation efficiency of the Fe-CO bond and theoretical references for experimental research.The only recently discovered gem-hydrogenation of internal alkynes is a fundamentally new transformation, in which both H atoms of dihydrogen are transferred to the same C atom of a triple bond while the other position transforms into a discrete metal carbene complex. [Cp*RuCl]4 is presently the catalyst of choice the resulting piano-stool ruthenium carbenes can engage a tethered alkene into either cyclopropanation or metathesis, and a prototypical example of such a reactive intermediate with an olefin ligated to the ruthenium center has been isolated and characterized by X-ray diffraction. It is the substitution pattern of the olefin that determines whether metathesis or cyclopropanation takes place a systematic survey using alkenes of largely different character in combination with a computational study of the mechanism at the local coupled cluster level of theory allowed the preparative results to be sorted and an intuitive model with predictive power to be proposed. This model links the course of the reace.We show that the self-assembly of monodisperse CdSe nanocrystals synthesized at lower temperature (∼310 °C) into three-dimensional supercrystals results in the formation of separate regions within the supercrystals that display photoluminescence at two distinctly different wavelengths. Specifically, the central portions of the supercrystals display photoluminescence and absorption in the orange region of the spectrum, around 585 nm, compared to the 575 nm photoluminescence maximum for the nanocrystals dispersed in toluene. Distinct domains on the surfaces and edges of the supercrystals, by contrast, display photoluminescence and absorption in the green region of the spectrum, around 570 nm. We attribute the different-colored domains to two subpopulations of NCs in the monodisperse ensemble the nanocrystals in the „orange” regions are chemically stable, whereas the nanocrystals in the „green” regions are partially oxidized. The susceptibility of the „green” nanocrystals to oxidation indicates a lower coverage of capping molecules on these nanocrystals. We propose that the two subpopulations correspond to nanocrystals with different surfaces that we attribute to the polytypism of CdSe.The first vertical ionization energy of an atom or molecule is encoded in the rate of exponential decay of the exact natural orbitals. For natural orbitals represented in terms of Gaussian basis functions, this property does not hold even approximately. We show that it is nevertheless possible to deduce the first ionization energy from the long-range behavior of Gaussian-basis-set wave functions by evaluating the asymptotic limit of a quantity called the average local electron energy (ALEE), provided that the most diffuse functions of the basis set have a suitable shape and location. The ALEE method exposes subtle qualitative differences between seemingly analogous Gaussian basis sets and complements the extended Koopmans theorem by being robust in situations where the one-electron reduced density matrix is ill-conditioned.2-Aryl/alkylbenzofurans, which constitute an important subclass of naturally occurring lignans and neolignans, have attracted extensive synthetic efforts due to their useful biological activities and significant pharmacological potential. Herein, we report a general and efficient approach to divergent 2-arylbenzofurans through a one-pot synthesis of versatile 2-bromobenzofurans as key intermediates. Using this approach, the first total synthesis of a series of trisubstituted and tetrasubstituted benzofurans bearing the hydroxyethyl unit, including the natural compounds isolated from Lavandula agustifolia (1-3) and their non-natural derivatives (4-8), was accomplished. We also report a modified synthesis of ailanthoidol, homoegonol, and egonol that enables the divergent synthesis of their derivatives for future exploration. Among these, the representative phenolic natural compound 2 and its derivatives 7 and 5 induced apoptotic cell death related poly(ADP-ribose) polymerase (PARP) cleavage in MCF74, A549, PC3, HepG2, and Hep3B cancer cell lines. Additionally, the tumor suppressor protein p53 was also induced in p53 wild type cancer cells.As a large enveloped RNA virus, coronavirus is of considerable medical and veterinary significance, and anticoronavirus treatment is challenging due to its biodiversity and rapid variability. In this study, Au@Ag nanorods (Au@AgNRs) were successfully synthesized by coating AuNRs with silver and were shown for the first time to have activity against the replication of porcine epidemic diarrhea virus (PEDV). Viral titer analysis demonstrated that Au@AgNRs could inhibit PEDV infection by 4 orders of magnitude at 12 h post-infection, which was verified by viral protein expression analysis. The potential mechanism of action showed that Au@AgNRs could inhibit the entry of PEDV and decrease the mitochondrial membrane potential and caspase-3 activity. Additionally, we demonstrated that a large amount of virus proliferation can cause the generation of reactive oxygen species in cells, and the released Ag+ and exposed AuNRs by Au@AgNRs after the stimulation of reactive oxygen species has superior antiviral activity to ensure long-term inhibition of the PEDV replication cycle. The integrated results support that Au@AgNRs can serve as a potential therapeutic strategy to prevent the replication of coronavirus.The bicyclic ditopic linker 2,2′-biselenophene-5,5′-dicarboxylic acid (H 2 SpSp), specifically designed for metal-organic framework (MOF) construction, has been synthesized in good yield and fully characterized. The corresponding zirconium MOF (Zr-MOF) [Zr6O4(OH)4(SpSp)3.8Cl4.4] (1; where missing linkers are replaced by chloride anions as shown by X-ray fluorescence and elemental analysis) is isostructural with its bithiophene and bithiazole analogues. Starting from 1, an extension of the biselenophene-based Zr-MOF family has been successfully achieved, exploiting the structural analogy of the five-membered heterocycles selenophene, thiophene, and thiazole. Thus, three mixed-linker MOFs containing variable amounts of different bis(heterocyclic) dicarboxylic acids have been prepared and fully characterized the two double-mixed [Zr6O4(OH)4(SpSp)2.6(TpTp)1.3Cl4.2] (2; H2TpTp = 2,2′-bithiophene-5,5′-dicarboxylic acid) and [Zr6O4(OH)4(SpSp)2(TzTz)1.8Cl4.4] (3; H2TzTz = 2,2′-bithiazole-5,5′-dicarboxylic acid) materials, as well as the triple-mixed [Zr6O4(OH)4(SpSp)1.6(TpTp)1.2(TzTz)1.4Cl3.6] (4) compound. The four MOFs are luminescent under UV irradiation, exhibiting emission wavelengths falling in the blue-green visible region, as observed for their constitutive linkers. These materials open new horizons in the preparation of porous luminescent sensors or multicolor emitters for light-emitting diodes.Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral pathogen. Traditionally associated with self-limited respiratory, gastrointestinal, and conjunctival infections, mainly in immunocompromised patients, HAdV is currently considered to be a pathogen presenting significant morbidity and mortality in both immunosuppressed and otherwise healthy individuals. Currently available therapeutic options are limited because of their lack of effectivity and related side effects. In this context, there is an urgent need to develop effective anti-HAdV drugs with suitable therapeutic indexes. In this work, we identified new serinol-derived benzoic acid esters as novel scaffolds for the inhibition of HAdV infections. A set of 38 compounds were designed and synthesized, and their antiviral activity and cytotoxicity were evaluated. Four compounds (13, 14, 27, and 32) inhibited HAdV infection at low micromolar concentrations (2.82-5.35 μM). Their half maximal inhibitory concentration (IC50) values were lower compared to that of cidofovir, the current drug of choice. All compounds significantly reduced the HAdV DNA replication process, while they did not block any step of the viral entry. Our results showed that compounds 13, 14, and 32 seem to be targeting the expression of the E1A early gene. Moreover, all four derivatives demonstrated a significant inhibition of human cytomegalovirus (HCMV) DNA replication. This new scaffold may represent a potential tool useful for the development of effective anti-HAdV drugs.In the 5G era, for portable electronics to operate at high performance and low power levels, the incorporation of superior electromagnetic interference (EMI) shielding materials within the packages is of critical importance. A desirable wearable EMI shielding material is one that is lightweight, structurally flexible, air-permeable, and able to self-clean. To this end, a bioinspired electroless silver plating strategy and a one-step electrodeposition method are utilized to prepare an EMI shielding fabric (CEF-NF/PDA/Ag/50-30) that possesses these desirable properties. Porous CEF-NF mats with a spatially distributed silver coating create efficient pathways for electron movement and enable a remarkable conductivity of 370 S mm-1. When tested within a frequency range of 8.2-12.4 GHz, this highly conductive fabric not only achieves an EMI shielding effectiveness (EMI SE of 101.27 dB at 5028 dB cm2 g-1) comparable to a very thin and light metal but also retains the unique properties of fabrics-being light, structurally flexible, and breathable. In addition, it exhibits a high contact angle (CA) of 156.4° with reversible surface wettability. After having been subjected to 1000 cycles of bending, the performance of the fabric only decreases minimally. This strategy potentially provides a novel way to design and manufacture an easily integrated EMI shielding fabric for flexible wearable devices.Thiolate-gold nanoclusters have various applications. However, most of the synthesis methods require prolonged synthesis times from several hours to days. In the present study, we report a rapid synthesis method for [Au25(Cys)18] nanoclusters and their application for photobactericidal enhancement. For [Au25(Cys)18] synthesis, we employed a tube-in-tube membrane reactor using CO as a reducing agent at elevated temperatures. This approach allows continuous generation of high-quality [Au25(Cys)18] within 3 min. Photobactericidal tests against Staphylococcus aureus showed that crystal violet-treated polymer did not have photobactericidal activity, but addition of [Au25(Cys)18] in the treated polymer demonstrated a potent photobactericidal activity at a low white light flux, resulting in >4.29 log reduction in viable bacteria numbers. Steady-state and time-resolved photoluminescence spectroscopies demonstrated that after light irradiation, photoexcited electrons in crystal violet flowed to [Au25(Cys)18] in the silicone, suggesting that redox reaction from [Au25(Cys)18] enhanced the photobactericidal activity. Stability tests revealed that leaching of crystal violet and [Au25(Cys)18] from the treated silicone was negligible and cyclic testing showed that the silicone maintained a strong photobactericidal activity after repeated use.Charge transfer across conjugated organic molecules is the functional basis of many optoelectronic and semiconductor devices. The ability to design such molecules to suit a given device application is highly desirable; yet, realizing this prospect is impeded by the lack of an algorithm that quantifies the extent of intramolecular charge transfer (ICT) in absolute terms. In turn, an algorithm to describe ICT is held back by a poor definition of one of its key dependent terms conjugation. Current equations assume that π-bonding operates solely across two bonds, even though conjugation extends beyond these limits, and such equations only yield relative measures of π-conjugation. This work presents a four-step algorithm that enumerates ICT on an absolute scale. The method is applied successfully to four types of optoelectronic materials; results demonstrate the need to reconsider certain fundamental chemical-bonding and ICT concepts for conjugated molecules. These findings have implications for all optoelectronic and semiconducting materials.The variational quantum eigensolver (VQE) is one of the most appealing quantum algorithms to simulate electronic structure properties of molecules on near-term noisy intermediate-scale quantum devices. In this work, we generalize the VQE algorithm for simulating periodic systems. However, the numerical study of a one-dimensional (1D) infinite hydrogen chain using existing VQE algorithms shows a remarkable deviation of the ground-state energy with respect to the exact full configuration interaction (FCI) result. Here, we present two schemes to improve the accuracy of quantum simulations for periodic systems. The first one is a modified VQE algorithm, which introduces a unitary transformation of Hartree-Fock orbitals to avoid the complex wave function. The second one is combining VQE with the quantum subspace expansion approach (VQE/QSE). Numerical benchmark calculations demonstrate that both of the two schemes provide an accurate description of the potential energy curve of the 1D hydrogen chain. In addition, excited states computed with the VQE/QSE approach also agree very well with FCI results.The inadequate clinical efficacy of the present anti-Alzheimer’s disease (AD) drugs and their low impact on the progression of Alzheimer’s disease in patients have revised the research focus from single targets to multitarget-directed ligands. A novel series of substituted triazinoindole derivatives were obtained by introducing various substituents on the indole ring for the development of multitarget-directed ligands as anti-AD agents. The experimental data indicated that some of these compounds exhibited significant anti-AD properties. Among them, 8-(piperidin-1-yl)-N-(6-(pyrrolidin-1-yl)hexyl)-5H-[1,2,4]triazino[5,6-b]indol-3-amine (60), the most potent cholinesterase inhibitor (AChE, IC50 value of 0.32 μM; BuChE, IC50 value of 0.21 μM), was also found to possess significant self-mediated Aβ1-42 aggregation inhibitory activity (54% at 25 μM concentration). Additionally, compound 60 showed strong antioxidant activity. In the PAMPA assay, compound 60 exhibited blood-brain barrier penetrating ability. An acute toxicity study in rats demonstrated no sign of toxicity at doses up to 2000 mg/kg. Furthermore, compound 60 significantly restored the cognitive deficits in the scopolamine-induced mice model and Aβ1-42-induced rat model. In the in silico ADMET prediction studies, the compound satisfied all the parameters of CNS acting drugs. These results highlighted the potential of compound 60 to be a promising multitarget-directed ligand for the development of potential anti-AD drugs.When subjected to arylboranes, anionic trifluoromethyl and difluorobenzyl palladium(II) complexes undergo fluoride abstraction followed by 1,1-migratory insertion. The resulting intermediate fluoroalkyl species can be induced to undergo a subsequent transmetalation and reductive elimination from either an in situ formed fluoroboronate (FB(Ar3)-) or an exogenous boronic acid/ester (ArB(OR)2) and nucleophilic activator, representing a net defluorinative arylation reaction. The latter method enabled a structurally diverse substrate scope to be prepared from either an isolated palladium-CF3 complex, or from Pd(PPh3)4 and other commercially available reagents.Nanostructuring and metal-support interactions have been explored as effective methods to improve the electrocatalytic activity in heterogeneous catalysis. In this study, we have fabricated ultrasmall Ru nanoparticles (NPs) dispersed on S-doped graphene (denoted as Ru/S-rGO) by a facile „one-pot” procedure. The experimental results indicated that both the S doping and moderate degree of oxidization of GO can induce the formation and high dispersion of the ultrasmall Ru NPs with larger electrochemically active surface areas for exposing more active sites. Metal-support interaction between S-doped graphene and Ru NPs was observed from the X-ray photoelectron spectroscopy and electronic charge-difference studies. It resulted in the decrease in the electron density of Ru, which facilitated electron release from H2O and H-OH bond breakage. The results of density functional theory calculation confirmed that the S-dopants could reduce the energy barrier for breaking the H-OH bond to accelerate water dissociation during the alkaline hydrogen evolution reaction (HER). At a current density 20 mA cm-2, the lowest overpotential of 14 mV, superior to that of Pt/C in alkaline solution, was observed for Ru/S-rGO-24. The observed lowest value of overpotential was because of the ultrasmall size, high dispersion, and metal-support interaction. This work provides a simple and effective method in designing advanced electrocatalysts for the HER in an alkaline electrolyte.The thermoelectric efficiency of skutterudite materials can be improved by lowering the lattice thermal conductivity via the uniform dispersion of a nanosized second phase in the matrix of filled Co4Sb12. In this work, nanocomposites of Ba0.3Co4Sb12 and InSb were synthesized using ball-milling and spark plasma sintering. The thermoelectric transport properties were studied from 4.2 to 773 K. The InSb nanoparticles of ∼20 nm were found to be dispersed in the Ba0.3Co4Sb12 grains with a few larger grains of about 10 μm due to the agglomeration of the InSb nanoparticles. The +2 oxidation state of Ba in Co4Sb12 resulted in a low electrical resistivity, ρ, value of the matrix. The enhancement of the Seebeck coefficient, S, and the electrical resistivity values of Ba0.3Co4Sb12 with the addition of InSb can be credited to the energy-filtering effect of electrons with low energy at the interfaces. The power factor of the composites could not be enhanced compared to the matrix because of the very high ρ value. A minimum possible lattice thermal conductivity (0.45 W/m·K at 773 K) was achieved due to the combined effect of rattling of Ba atoms in the voids and enhanced phonon scattering at the interfaces induced by nanosized InSb particles. As a result, the (InSb)0.15 + Ba0.3Co4Sb12 composite exhibited improved thermoelectric properties with the highest zT of 1.4 at 773 K and improved mechanical properties with a higher hardness, higher Young’s modulus, and lower brittleness.We report a case of a 55-year-old male admitted for cardiogenic embolic ischemic stroke work up. A transesophageal (TE) echocardiography (E) with contrast study to rule out patent foramen ovale (PFO) was performed; two-dimensional (2D) analysis did not detect any bubbles passage during Valsalva manoeuvre in the standard 2D cross sectional planes; further real time three-dimensional (3D) TEE imaging revealed passage of bubbles in the left atrium (LA) by both real-time 3DTEE imaging and by the 2D unconventional cross-sectional planes allowed by 3DTEE imaging. Even though 2DTEE is considered to be the gold standard modality for diagnosing PFO, it has some limitations. It has never been reported about usefulness of 3DTEE in PFO imaging. Even in the presence of only a report, our case suggests that 3DE could have an additional value and will compliment 2D imaging in PFO assessment.

Nuclear medicine plays a crucial role for personalized therapy, mainly in oncology. Chemotherapy and radiotherapy present some disadvantages and research is shifting toward nanotechnology with significant improvements in therapy and diagnosis of several cancers. Indeed, nanoparticles can be tagged with different radioisotopes for single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging and for therapy. This review describes the current state of the art of

Copper-labeled nanoparticles for PET imaging of cancer.

We performed a systematic analysis of literature using the terms „64CuCl<inf>2</inf>,” „64Cu,” „Copper” AND „nanoparticle” AND „PET” in online databases i.e. PubMed/MEDLINE and Scopus. The search was limited to English papers and original articles. We excluded articles not in English language, abstracts, case reports, review articles and meeting presentations.

Amongst the 116 articles retrieved, 88 were excluded because reviews, or not in English, or only in-vitro studies or meeting presentations. We considered only 28 original papers. The most used nanoparticles are liposomes and they are mainly used in breast cancer although other animal models of cancer have been also investigated.

The results showed that nanoparticles can be considered a promising radiopharmaceutical for PET imaging of different type of cancer.

The results showed that nanoparticles can be considered a promising radiopharmaceutical for PET imaging of different type of cancer.

Biobanks are imperative infrastructures, particularly during outbreaks, when there is an obligation to acquire and share knowledge as quick as possible to allow for implementation of science-based preventive, diagnostic, prognostic and therapeutic strategies.

We established a COVID-19 biobank with the aim of collecting high-quality and well-annotated human biospecimens, in the effort to understand the pathogenic mechanisms underlying COVID-19 and identify therapeutic targets (COVID-BioB, NCT04318366). Here we describe our experience and briefly review the characteristics of the biobanks for COVID-19 that have been so far established.

A total of 46,677 samples have been collected from 913 participants (63.3% males, median [IQR] age 62.2 [51.2 – 74.0] years) since the beginning of the program. Most patients (66.9%) had been admitted to hospital for COVID-19, with a median length of stay of 15.0 (9.0 – 27.0) days. A minority of patients (13.3% of the total) had been admitted for other reasons and subsequently tested positive for SARS-CoV-2. The remainder were managed at home after being seen at the Emergency Department.

Having a solid research infrastructure already in place, along with flexibility and adaptability to new requirements, allowed for the quick building of a COVID-19 biobank that will help expand and share the knowledge of SARS-CoV-2.

Having a solid research infrastructure already in place, along with flexibility and adaptability to new requirements, allowed for the quick building of a COVID-19 biobank that will help expand and share the knowledge of SARS-CoV-2.Chronic hepatitis B virus (HBV) infection encompasses a wide virologic and clinical spectrum with heterogeneous outcomes. The natural history of chronic HBV infection ranges from an inactive carrier state (hepatitis B e antigen-negative chronic infection) to progressive chronic hepatitis that may evolve in end-stage liver disease and hepatocellular carcinoma. The issue becomes even more complicated when we consider the unique biology of the virus; the HBV covalently-closed-circular DNA, that acts as virus transcription template, is the key factor responsible of the persistence of the infection even after hepatitis B surface antigen loss. In the last decade, novel serological and immunological biomarkers associated to the core protein of HBV have been approached in different clinical conditions. Remarkable results have been obtained both in the setting of overt and occult HBV infection. Here, we reviewed the meaning and the potential clinical applications of the measurement of core antigen and antibodies.The ongoing global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been posing challenges to proper patients’ management. Lungs are the first, and often the most affected organ by SARS-CoV-2; viral infection involves and damages both epithelial and vascular compartments, sometimes leading to severe and even fatal acute respiratory distress syndrome. Histopathological findings, mainly from postmortem examination of COVID-19 deceased patients, have been increasingly published in the last few months, helping to elucidate the sequence of events resulting in organ injury, and the complex multifactorial pathogenesis of this novel disease. A multidisciplinary approach to autopsy, including light microscopy examination along with the detection of viral proteins and/or RNA in tissue samples through ancillary techniques, provided crucial information on the mechanisms underlying the often-heterogeneous clinical picture of COVID-19.

The aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.

We searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915).

From 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria.equired to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events.

Due to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events.This article is the second in a series on asthma. The first article identified that the UK is experiencing an 'epidemic’ of childhood asthma and one of the major culprits is air pollution. This article examines the main causes of air pollution and how they affect the lung health of children from before birth and onwards. It considers the contribution of indoor and outdoor air pollution, how these have changed over time and the unequal effect they may have on vulnerable populations. The nurse’s role is discussed, not only in terms of clinical care, but also as adviser to families and schools on what actions to take to limit their exposure and reduce their own emissions of pollutants.The insertion of an indwelling urethral urinary catheter is an invasive procedure that is commonly undertaken in healthcare settings. However, there are several risks and potential complications associated with these devices, so their use should be avoided where possible. It is important that nurses are equipped with the necessary knowledge and skills not only to assess if a patient requires a catheter, but also to minimise the risk of associated complications and to understand how these can be managed. This article discusses some of the common complications that can occur with the use of indwelling urinary catheters, including catheter-associated urinary tract infections; catheter blockages; encrustation; negative pressure; bladder spasm and trauma; and, in men, paraphimosis. It also explains the steps that nurses can take to reduce the risk of these complications and how to manage them effectively.The newest generation of drug delivery systems (DDSs) exploits ligands to mediate specific targeting of cells and/or tissues. However, studies investigating the link between ligand density and nanoparticle (NP) uptake are limited to a small number of ligand-receptor systems. C-type lectin-like molecule-1 (CLL1) is uniquely expressed on myeloid cells, which enables the development of receptors specifically targeting treat various diseases. This study aims to investigate how NPs with different CLL1 targeting peptide density impact cellular uptake. To this end, poly(styrene-alt-maleic anhydride)-b-poly(styrene) NPs are functionalized with cyclized CLL1 binding peptides (cCBP) ranging from 240 ± 12 to 31 000 ± 940 peptides per NP. Unexpectedly, the percentage of cells with internalized NPs is decreased for all cCBP-NP designs regardless of ligand density compared to unmodified NPs. Internalization through CLL1 receptor-mediated processes is further investigated without confounding the effects of NP size and surface charge. Interestingly, high density cCBP-NPs (>7000 cCBP per NP) uptake is dominated by CLL1 receptor-mediated processes while low density cCBP-NPs (≈200 cCBP per NP) and untargeted NP occurred through non-specific clathrin and caveolin-mediated endocytosis. Altogether, these studies show that ligand density and uptake mechanism should be carefully investigated for specific ligand-receptor systems for the design of targeted DDSs to achieve effective drug delivery.The heterogeneous and anisotropic articular cartilage is generally studied as a layered structure of „zones” with unique composition and architecture, which is difficult to recapitulate using current approaches. A novel hybrid bioprinting strategy is presented here to generate zonally stratified cartilage. Scaffold-free tissue strands (TSs) are made of human adipose-derived stem cells (ADSCs) or predifferentiated ADSCs. Cartilage TSs with predifferentiated ADSCs exhibit improved mechanical properties and upregulated expression of cartilage-specific markers at both transcription and protein levels as compared to TSs with ADSCs being differentiated in the form of strands and TSs of nontransfected ADSCs. Using the novel hybrid approach integrating new aspiration-assisted and extrusion-based bioprinting techniques, the bioprinting of zonally stratified cartilage with vertically aligned TSs at the bottom zone and horizontally aligned TSs at the superficial zone is demonstrated, in which collagen fibers are aligned with designated orientation in each zone imitating the anatomical regions and matrix orientation of native articular cartilage. In addition, mechanical testing study reveals a compression modulus of ≈1.1 MPa, which is similar to that of human articular cartilage. The prominent findings highlight the potential of this novel bioprinting approach for building biologically, mechanically, and histologically relevant cartilage for tissue engineering purposes.

Platinum-based chemotherapy is currently the most frequently applied first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) without targetable mutations or high PD-L1 expression. Unfortunately, chemotherapy-induced toxicity is prevalent and may affect patients’ quality of life to a considerable extent. Presumably, genetic variants of genes, coding for proteins involved in the processes of the development of toxicity, may be of interest as predictors of benefits and harms of platinum-based chemotherapy. The primary objective of the study is to investigate the influence of genetic variants on the incidence of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy. The main secondary objectives are to study the association between genetic variants and treatment response and to study the association between skeletal muscle mass (SMM) as well as patient-reported health-related quality of life (HRQOL) and treatment response and toxicity.

ce of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy.T lymphocytes are the central coordinator and executor of many immune functions. The activation and function of T lymphocytes are mediated through the engagement of cell surface receptors and regulated by a myriad of intracellular signaling network. Bioengineering tools, including imaging modalities and fluorescent probes, have been developed and employed to elucidate the cellular events throughout the functional lifespan of T cells. A better understanding of these events can broaden our knowledge in the immune systems biology, as well as accelerate the development of effective diagnostics and immunotherapies. Here we review the commonly used and recently developed techniques and probes for monitoring T lymphocyte intracellular events, following the order of intracellular events in T cells from activation, signaling, metabolism to apoptosis. The techniques introduced here can be broadly applied to other immune cells and cell systems. This article is categorized under Immune System Diseases > Molecular and Cellular Physiology Immune System Diseases > Biomedical Engineering Infectious Diseases > Biomedical Engineering.Drug-drug interactions (DDIs) occur when the pharmacological activity of one drug is altered by a second drug. As multimorbidity and polypharmacotherapy are becoming more common due to the increasing age of the population, the risk of DDIs is massively increasing. Therefore, in vitro testing methods are needed to capture such multiorgan events. Here, a scalable, gravity-driven microfluidic system featuring 3D microtissues (MTs) that represent different organs for the prediction of drug-drug interactions is used. Human liver microtissues (hLiMTs) are combined with tumor microtissues (TuMTs) and treated with drug combinations that are known to cause DDIs in vivo. The testing system is able to capture and quantify DDIs upon co-administration of the anticancer prodrugs cyclophosphamide or ifosfamide with the antiretroviral drug ritonavir. Dosage of ritonavir inhibits hepatic metabolization of the two prodrugs to different extents and decreases their efficacy in acting on TuMTs. The flexible MT compartment design of the system, the use of polystyrene as chip material, and the assembly of several chips in stackable plates offer the potential to significantly advance preclinical substance testing. The possibility of testing a broad variety of drug combinations to identify possible DDIs will improve the drug development process and increase patient safety.Tissue engineered vascular grafts (TEVGs) are a promising technology, but are hindered by occlusion. Seeding with bone-marrow derived mononuclear cells (BM-MNCs) mitigates occlusion, yet the precise mechanism remains unclear. Seeded cells disappear quickly and potentially mediate an anti-inflammatory effect through paracrine signaling. Here, a series of reciprocal genetic TEVG implantations plus recombinant protein treatment is reported to investigate what role interleukin-10, an anti-inflammatory cytokine, plays from both host and seeded cells. TEVGs seeded with BM-MNCs from wild-type and IL-10 KO mice, plus unseeded grafts, are implanted into wild-type and IL-10 KO mice. Wild-type mice with unseeded grafts also receive recombinant IL-10. Serial ultrasound evaluates occlusion and TEVGs are harvested at 14 d for immunohistochemical analysis. TEVGs in IL-10 KO mice have significantly higher occlusion incidence compared to wild-type mice attributed to acute ( less then 3 d) thrombosis. Cell seeding rescues TEVGs in IL-10 KO mice comparable to wild-type patency. IL-10 from the host and seeded cells do not significantly influence graft inflammation and macrophage phenotype, yet IL-10 treatment shows interesting biologic effects including decreasing cell proliferation and increasing M2 macrophage polarization. IL-10 from the host is critical for preventing TEVG thrombosis and seeded BM-MNCs exert a significant anti-thrombotic effect in IL-10 KO mice.The purpose of the current study was to examine the prevalence of attention deficit hyperactivity disorder (ADHD) symptoms among young children with autism spectrum disorder (ASD), child and parent-related demographic and clinical correlates of ADHD symptoms, and the relationships between co-occurring mental health problems and ADHD symptoms. Data for this cross-sectional study came from 979 toddlers and preschoolers, ages 1.5-5 years, with ASD. The primary outcome, ADHD symptoms, was measured using the Child Behavior Check List 1.5-5 (CBCL). Additional information from the medical record included demographics, parenting stress, and Autism Diagnostic Observation Schedule Second Edition. Descriptive and bivariate (ANOVA, Chi-Square) statistics and multivariate, multinomial regression analyses were used to examine demographic and clinical differences between low, moderate, and high ADHD symptom groups, as defined by 2 ADHD-related subscales. There were 418 (43%) children in the low ADHD symptom group, 294 (30%) stress and greater level of other psychopathologies, both internalizing and externalizing problems.Osteocytes are mechanosensitive cells that orchestrate signaling in bone and cartilage across the osteochondral unit. The mechanisms by which osteocytes regulate osteochondral homeostasis and degeneration in response to mechanical cues remain unclear. This study introduces a novel 3D hydrogel bilayer composite designed to support osteocyte differentiation and bone matrix deposition in a bone-like layer and to recapitulate key aspects of the osteochondral unit’s complex loading environment. The bilayer hydrogel is fabricated with a soft cartilage-like layer overlaying a stiff bone-like layer. The bone-like layer contains a stiff 3D-printed hydrogel structure infilled with a soft, degradable, cellular hydrogel. The IDG-SW3 cells embedded within the soft hydrogel mature into osteocytes and produce a mineralized collagen matrix. Under dynamic compressive strains, near-physiological levels of strain are achieved in the bone layer (≤ 0.08%), while the cartilage layer bears the majority of the strains (>99%). Under loading, the model induces an osteocyte response, measured by prostaglandin E2, that is frequency, but not strain, dependent a finding attributed to altered fluid flow within the composite. Overall, this new hydrogel platform provides a novel approach to study osteocyte mechanobiology in vitro in an osteochondral tissue-mimetic environment.Evidences indicate that the decline of female fertility is becoming a common problem over the past few decades. Environmental exposure of Bisphenol A (BPA) has been considered as an endocrine-disrupting chemical deleteriously affecting human reproductions. To better understand the effect of BPA exposure on human ovarian granulosa cells, we treated human ovarian granulosa cell line (KGN) with increasing concentrations (0.1, 1, 10, and 100 μM) of BPA for 24 hr. About 0.1, 1, and 10 μM BPA did not significantly affect the viability of KGN while 100 μM of BPA caused a statistically significant decrease in the viability of KGN. Treatment KGN with 10 μM BPA resulted in a significant decrease in progesterone biosynthesis. The treatment also significantly increased the expression of ATP binding cassette subfamily A member 1 (ABCA1) and steroidogenic acute regulatory protein (STAR). In the current study, exposure to BPA could lead to decreased progesterone production probably through the upregulation of ABCA1 in human granulosa cells.Activating mutations in RAS are present in ~ 30% of human tumors, and the resulting aberrations in ERK/MAPK signaling play a central role in oncogenesis. However, the form of these signaling changes is uncertain, with activating RAS mutants linked to both increased and decreased ERK activation in vivo. Rationally targeting the kinase activity of this pathway requires clarification of the quantitative effects of RAS mutations. Here, we use live-cell imaging in cells expressing only one RAS isoform to quantify ERK activity with a new level of accuracy. We find that despite large differences in their biochemical activity, mutant KRAS isoforms within cells have similar ranges of ERK output. We identify roles for pathway-level effects, including variation in feedback strength and feedforward modulation of phosphatase activity, that act to rescale pathway sensitivity, ultimately resisting changes in the dynamic range of ERK activity while preserving responsiveness to growth factor stimuli. Our results reconcile seemingly inconsistent reports within the literature and imply that the signaling changes induced by RAS mutations early in oncogenesis are subtle.

To help differentiate CLN3 (Batten) disease, a devastating childhood metabolic disorder, from the similarly presenting early-onset Stargardt disease (STGD1). Early clinical identification of children with CLN3 disease is essential for adequate referral, counselling and rehabilitation.

Medical chart review of 38 children who were referred to a specialized ophthalmological centre because of rapid vision loss. The patients were subsequently diagnosed with either CLN3 disease (18 patients) or early-onset STGD1 (20 patients).

Both children who were later diagnosed with CLN3 disease, as children who were later diagnosed with early-onset STGD1, initially presented with visual acuity (VA) loss due to macular dystrophy at 5-10years of age. VA in CLN3 disease decreased significantly faster than in STGD1 (p=0.01). Colour vision was often already severely affected in CLN3 disease while unaffected or only mildly affected in STGD1. Optic disc pallor on fundoscopy and an abnormal nerve fibre layer on optical coherence tomography were common in CLN3 disease compared to generally unaffected in STGD1. In CLN3 disease, dark-adapted (DA) full-field electroretinogram (ERG) responses were either absent or electronegative. In early-onset STGD1, DA ERG responses were generally unaffected. None of the STGD1 patients had an electronegative ERG.

Already upon presentation at the ophthalmologist, the retina in CLN3 disease is more extensively and more severely affected compared to the retina in early-onset STGD1. This results in more rapid VA loss, severe colour vision abnormalities and abnormal DA ERG responses as the main differentiating early clinical features of CLN3 disease.

Already upon presentation at the ophthalmologist, the retina in CLN3 disease is more extensively and more severely affected compared to the retina in early-onset STGD1. This results in more rapid VA loss, severe colour vision abnormalities and abnormal DA ERG responses as the main differentiating early clinical features of CLN3 disease.Collagen is the most abundant extracellular matrix protein that is widely used in tissue engineering (TE). There is little research done on printing pure collagen. To understand the bottlenecks in printing pure collagen, it is imperative to understand collagen from a bottom-up approach. Here it is aimed to provide a comprehensive overview of collagen printing, where collagen assembly in vivo and the various sources of collagen available for TE application are first understood. Next, the current printing technologies and strategy for printing collagen-based materials are highlighted. Considerations and key challenges faced in collagen printing are identified. Finally, the key research areas that would enhance the functionality of printed collagen are presented.The size, shape, and underlying chemistries of drug delivery particles are key parameters which govern their ultimate performance in vivo. Responsive particles are desirable for triggered drug delivery, achievable through architecture change and biodegradation to control in vivo fate. Here, polymeric materials are synthesized with linear, hyperbranched, star, and micellar-like architectures based on 2-hydroxypropyl methacrylamide (HPMA), and the effects of 3D architecture and redox-responsive biodegradation on biological transport are investigated. Variations in „stealth” behavior between the materials are quantified in vitro and in vivo, whereby reduction-responsive hyperbranched polymers most successfully avoid accumulation within the liver, and none of the materials target the spleen or lungs. Functionalization of selected architectures with doxorubicin (DOX) demonstrates enhanced efficacy over the free drug in 2D and 3D in vitro models, and enhanced efficacy in vivo in a highly aggressive orthotopic breast cancer model when dosed over schedules accounting for the biodistribution of the carriers. These data show it is possible to direct materials of the same chemistries into different cellular and physiological regions via modulation of their 3D architectures, and thus the work overall provides valuable new insight into how nanoparticle architecture and programmed degradation can be tailored to elicit specific biological responses for drug delivery.

To compare the clinical outcomes of plate fixation and arthroscopic-assisted plate fixation in patients with displaced isolated medium-sized fractures of the greater tuberosity.

From July 2013 to October 2017, patients with displaced isolated medium-sized fractures of the greater tuberosity who underwent arthroscopic-assisted plate fixation (ASPF group) or open reduction and internal plate fixation (ORIF group) were retrospectively reviewed and analyzed. There were 19 patients in the ASPF group and 27 patients in the ORIF group, with comparable demographic characteristics. The average age of patients was 49.4 ± 12.1 years in the ASPF group and 46.9 ± 11.4 years in the ORIF group. The shoulder function reflected by the Constant-Murley (CS) scores, the American Shoulder and Elbow Surgeons (ASES) scores, and the range of motion (ROM) in the both groups at the last follow-up were analyzed in the study. Surgery time, postoperative pain, and postoperative complications were also reviewed.

A total of 46 eligibacture nonunion, pullout of the suture anchor, and screw penetration, were not observed in either group.

Arthroscopic-assisted plate fixation is effective and may be an alternative in the treatment of displaced isolated medium-sized fractures of the greater tuberosity.

Arthroscopic-assisted plate fixation is effective and may be an alternative in the treatment of displaced isolated medium-sized fractures of the greater tuberosity.

Like other autoimmune diseases, systemic sclerosis (SSc) has been described to be associated with accelerated atherosclerosis (ATS). Before clinical manifestations of cardiovascular disease (CVD) occur, subclinical ATS can be investigated in different ways.

To evaluate the presence of subclinical ATS in a group of patients with SSc, and to identify different risk profiles among patients.

Subclinical ATS was reviewed in 43 SSc patients and 27 healthy controls, using 2 methods carotid ultrasound and flow mediated dilation (FMD) of the brachial artery.

Plaques were statistically more frequent in SSc patients than in controls (65% vs 30%, P=.006); intima-media thickness of common carotid artery (CCA-IMT) resulted in statistically higher (median value 0.8mm vs 0.55mm; P<.0001) while FMD was significantly lower (median value 9% vs 14%; P=.0086) in patients compared to healthy controls. Among the SSc patients, thickening of CCA-IMT was significantly associated with the presence of diastolic dysfunction of left ventricle (absence of diastolic dysfunction odds ratio [OR] 0.