bluuebunny/crossref_metadata_2025 huggingface dataset:
Molnupiravir and risk of post-acute sequelae of covid-19: cohort study
Authors: Xie Yan , Choi Taeyoung , Al-Aly Ziyad
Published: April 2023

Objective

To examine whether treatment with the antiviral agent molnupiravir during the first five days of SARS-CoV-2 infection is associated with reduced risk of post-acute adverse health outcomes.

Design

Cohort study.

Setting

US Department of Veterans Affairs.

Participants

229 286 participants who tested positive for SARS-CoV-2 between 5 January 2022 and 15 January 2023, had at least one risk factor for progression to severe covid-19, and survived the first 30 days after testing positive were enrolled. 11 472 participants received a prescription for molnupiravir within five days of the positive test result and 217 814 received no covid-19 antiviral or antibody treatment (no treatment group).

Main outcome measures

Risks of post-acute sequelae of SARS-CoV-2 (PASC, defined based on a prespecified set of 13 post-acute sequelae), post-acute death, post-acute hospital admission, and each individual post-acute sequela between the molnupiravir group and no treatment group were examined after application of inverse probability weighting to balance the treatment and no treatment groups. Post-acute outcomes were ascertained from 30 days after the first SARS-CoV-2 positive test result until end of follow-up. Risks on the relative scale (relative risk or hazard ratio) and absolute scale (absolute risk reduction at 180 days) were estimated.

Results

Compared with no treatment, molnupiravir use within five days of a positive SARS-CoV-2 test result was associated with reduced risk of PASC (relative risk 0.86 (95% confidence interval 0.83 to 0.89); absolute risk reduction at 180 days 2.97% (95% confidence interval 2.31% to 3.60%)), post-acute death (hazard ratio 0.62 (0.52 to 0.74); 0.87% (0.62% to 1.13%)), and post-acute hospital admission (0.86 (0.80 to 0.93); 1.32% (0.72% to 1.92%)). Molnupiravir was associated with reduced risk of eight of the 13 post-acute sequelae: dysrhythmia, pulmonary embolism, deep vein thrombosis, fatigue and malaise, liver disease, acute kidney injury, muscle pain, and neurocognitive impairment. Molnupiravir was also associated with reduced risk of PASC in people who had not received a covid-19 vaccine, had received at one or two vaccine doses, and had received a booster dose, and in people with primary SARS-CoV-2 infection and reinfection.

Conclusions

In people with SARS-CoV-2 infection and at least one risk factor for progression to severe covid-19, compared with no treatment, molnupiravir use within five days of infection was associated with reduced risk of PASC in people who had not received a covid-19 vaccine, had received one or two vaccine doses, and had received a booster dose, and in those with primary SARS-CoV-2 infection and reinfection. Among people at high risk of progression to severe covid-19, molnupiravir use within five days of SARS-CoV-2 infection may be a viable approach to reduce the risk of PASC.
Food handlers’ knowledge, attitudes and self-reported practices regarding safe food handling in charitable food assistance programmes in the eThekwini District, South Africa: cross-sectional study
Authors: Makhunga Sizwe Earl , Macherera Margaret , Hlongwana Khumbulani
Published: April 2023

Objective

This study aimed to assess food handlers’ knowledge, attitudes and self-reported practices towards safer donated foods.

Design

This cross-sectional study was conducted from January to May 2021.

Setting

This study was conducted in the eThekwini District, South Africa.

Participants

A convenience sampling-based cross-sectional survey of food handlers (n=252) served as the study’s main source of data. A total of eight study sites across five municipal planning regions of eThekwini District were visited. The principal investigator administered the validated structured standardised questionnaire, using participants’ language of choice, which was either English or isiZulu. All the questions in the questionnaire were asked in exactly the same manner, following the same flow, in order to avoid bias and ensure consistency. Furthermore, the close-ended nature of questions in the questionnaire mitigated the risks of question manipulation. The questionnaire was adapted from the WHO’s five keys to a safer food manual.

Primary and secondary outcome measures

The primary outcome was the knowledge, attitudes and self-reported practices towards safer donated foods. The secondary outcomes were the sanitary conditions of infrastructure and facilities, food handlers’ observed food handling behaviour and nutritional information/labelling.

Results

The results show that the food handlers had good knowledge, positive attitude and acceptable behaviours towards safe food handling and general hygiene, with mean scores (SD) of 62.8 (14.6), 92.5 (14.1) and 80.4 (13.3), respectively. Significant correlations were found between knowledge and attitudes (p=0001), knowledge and practices (p<0001), and attitudes and practices (p=0.02). However, the correlations between knowledge versus attitude and attitude versus practice were poor (Spearman’s r<0.3), and the association between knowledge versus practice was moderate (0.3–0.7). The majority of food handlers (92.5%) did not understand the value of thorough cooking and temperature control. About 53% of respondents acknowledged to never adequately reheating cooked meals, 5% did not see the significance of preventing cross-contamination and 5% were unsure.

Conclusions

Despite the relatively positive knowledge, attitude and practice levels of the food handlers, safe food handling and hygiene practices, such as thorough cooking and temperature control, properly reheating cooked meals and taking precautions to prevent cross-contamination, require some emphasis.
Associations between autistic traits and early ear and upper respiratory signs: a prospective observational study of the Avon Longitudinal Study of Parents and Children (ALSPAC) geographically defined childhood population
Authors: Hall Amanda , Maw Richard , Iles-Caven Yasmin , Gregory Steven , Rai Dheeraj , Golding Jean
Published: April 2023

Objective

To determine whether early ear and upper respiratory signs are associated with the development of high levels of autistic traits or diagnosed autism.

Design

Longitudinal birth cohort: Avon Longitudinal Study of Parents and Children (ALSPAC).

Setting

Area centred on the city of Bristol in Southwest England. Eligible pregnant women resident in the area with expected date of delivery between April 1991 and December 1992 inclusive.

Participants

10 000+ young children followed throughout their first 4 years. Their mothers completed three questionnaires between 18–42 months recording the frequency of nine different signs and symptoms relating to the upper respiratory system, as well as ear and hearing problems.

Outcome measures

Primary—high levels of autism traits (social communication, coherent speech, sociability, and repetitive behaviour); secondary—diagnosed autism.

Results

Early evidence of mouth breathing, snoring, pulling/poking ears, ears going red, hearing worse during a cold, and rarely listening were associated with high scores on each autism trait and with a diagnosis of autism. There was also evidence of associations of pus or sticky mucus discharge from ears, especially with autism and with poor coherent speech. Adjustment for 10 environmental characteristics made little difference to the results, and substantially more adjusted associations were at p<0.001 than expected by chance (41 observed; 0.01 expected). For example, for discharge of pus or sticky mucus from ears the adjusted odds ratio (aOR) for autism at 30 months was 3.29 (95% CI 1.85 to 5.86, p<0.001), and for impaired hearing during a cold the aOR was 2.18 (95% CI 1.43 to 3.31, p<0.001).

Conclusions

Very young children exhibiting common ear and upper respiratory signs appear to have an increased risk of a subsequent diagnosis of autism or demonstrated high levels of autism traits. Results suggest the need for identification and management of ear, nose and throat conditions in autistic children and may provide possible indicators of causal mechanisms.
Building an understanding of Ethnic minority people’s Service Use Relating to Emergency care for injuries: the BE SURE study protocol
Authors: Baghdadi Fadi , Evans Bridie Angela , Goodacre Steve , John Paul Anthony , Hettiarachchi Thanuja , John Ann , Lyons Ronan A , Porter Alison , Safari Solmaz , Siriwardena Aloysius Niroshan , Snooks Helen , Watkins Alan , Williams Julia , Khanom Ashrafunnesa
Published: April 2023

Introduction

Injuries are a major public health problem which can lead to disability or death. However, little is known about the incidence, presentation, management and outcomes of emergency care for patients with injuries among people from ethnic minorities in the UK. The aim of this study is to investigate what may differ for people from ethnic minorities compared with white British people when presenting with injury to ambulance and Emergency Departments (EDs).

Methods and analysis

This mixed methods study covers eight services, four ambulance services (three in England and one in Scotland) and four hospital EDs, located within each ambulance service. The study has five Work Packages (WP): (WP1) scoping review comparing mortality by ethnicity of people presenting with injury to emergency services; (WP2) retrospective analysis of linked NHS routine data from patients who present to ambulances or EDs with injury over 5 years (2016–2021); (WP3) postal questionnaire survey of 2000 patients (1000 patients from ethnic minorities and 1000 white British patients) who present with injury to ambulances or EDs including self-reported outcomes (measured by Quality of Care Monitor and Health Related Quality of Life measured by SF-12); (WP4) qualitative interviews with patients from ethnic minorities (n=40) and focus groups—four with asylum seekers and refugees and four with care providers and (WP5) a synthesis of quantitative and qualitative findings.

Ethics and dissemination

This study received a favourable opinion by the Wales Research Ethics Committee (305391). The Health Research Authority has approved the study and, on advice from the Confidentiality Advisory Group, has supported the use of confidential patient information without consent for anonymised data. Results will be shared with ambulance and ED services, government bodies and third-sector organisations through direct communications summarising scientific conference proceedings and publications.
Association of trajectories of non-high-density lipoprotein cholesterol concentration with risk of cardiovascular disease: the Kailuan Study
Authors: Ding Xiong , Zhou Hui , Yue Qing , Shu Zhe , Ma Xiaoxu , Li Yun , Wu Shouling
Published: April 2023

Objectives

This study aimed to assess the association between longitudinal change in non-high-density lipoprotein cholesterol (non-HDL-C) and subsequent cardiovascular disease (CVD) risk.

Design

A retrospective study.

Setting

Data were obtained from the Kailuan Study, a dynamic cohort study initiated in 2006 in Tangshan, China.

Participants

The current study included 41 085 participants (mean age 53.9±11.6 years) free of CVD events in or before 2012. The non-HDL-C trajectory was developed according to the repeated measurement during 2006–2012 surveys to predict the CVD risk from 2012 to 2020.

Primary outcome measures

CVD events included myocardial infarction and stroke.

Results

3 discrete non-HDL-C trajectories were identified: low-increasing (n=20 038), moderate-increasing (n=17 987) and high-increasing (n=3060). During 8 years of follow-up, 1797 CVD events were documented. Relative to the low-increasing pattern, adjusted HRs were 1.25 (95% CI: 1.13 to 1.38) for the moderate-increasing pattern and 1.46 (95% CI: 1.24 to 1.71) for the high-increasing pattern after adjustment for potential confounders such as age, sex, education background, smoking status, drinking status, physical activity, body mass index, low-density lipoprotein cholesterol, hypertension, diabetes and lipid-lowering medications.

Conclusions

Changes in non-HDL-C were significantly associated with subsequent risk of CVD events, and participants with a high-increasing pattern had a higher CVD risk. Long-term monitoring of non-HDL-C could be useful to improve the prediction of CVD risk.

Trial registration number

ChiCTR-TNC-1100148.
A national longitudinal cohort study of factors contributing to UK medical students’ mental ill-health symptoms
Authors: Medisauskaite Asta , Silkens Milou E W M , Rich Antonia
Published: April 2023

Background

The mental health of current medical students is predictive of their mental health as future doctors. The prevalence of anxiety, depression and burnout is high among medical students, but less is known about the occurrence of other mental ill-health symptoms, such as eating or personality disorders, and factors contributing to mental ill-health.

Aims

(1) To explore the prevalence of various mental ill-health symptoms in medical students and (2) to investigate what medical school factors and students’ attitudes contribute to these mental ill-health symptoms.

Methods

Between November 2020 and May 2021, medical students from nine geographically spread medical schools in the UK participated by completing online questionnaires at two points in time, approximately 3 months apart.

Results

Of the 792 participants who filled in the questionnaire at baseline, over half experienced medium to high somatic symptoms (50.8%; 402) and drank alcohol at hazardous levels (62.4%; 494). Adjusted longitudinal data analysis of 407 students who completed the follow-up questionnaire demonstrated that less supportive educational climates that were more competitive and less centralised around the students, lower feelings of belongingness, greater stigma towards mental ill-health and lower intentions to seek help for mental ill-health, all contributed to students’ mental ill-health symptoms.

Conclusions

Medical students experience a high prevalence of various mental ill-health symptoms. This study suggests that medical school factors and students’ attitudes towards mental ill-health are significantly associated with students’ mental health.
Causal links between socioeconomic status, leisure sedentary behaviours and gastro-oesophageal reflux disease: a multivariable two-sample Mendelian randomisation study
Authors: Lian Xingji , Lin Yifen , Peng Xiaohui , Wang Yanhui , He Ting , He Ziyong , Gu Wenlong , Wang Hongwu , He Feng , Huang Yuyu
Published: April 2023

Introduction

We implemented a two-sample multivariable Mendelian randomisation (MR) analyses to estimate the causal effect of socioeconomic status and leisure sedentary behaviours on gastro-oesophageal reflux disease (GERD).

Methods

Independent single-nucleotide polymorphisms associated with socioeconomic status and leisure sedentary behaviours at the genome-wide significance level from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) UK Biobank were selected as instrumental variables. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. Univariable and multivariable two-sample MR analyses, using inverse variance weighted method for primary analyses, were performed to jointly evaluate the effect of socioeconomic status and leisure sedentary behaviours on GERD risk.

Results

Three socioeconomic status, including educational attainment (OR 0.46; 95% CI 0.30 to 0.69; p<0.001), average total household income before tax (OR 0.65; 95% CI 0.47 to 0.90; p=0.009) and Townsend Deprivation Index at recruitment (OR 1.60; 95% CI 1.06 to 2.41; p=0.026), were independently and predominately responsible for the genetic causal effect on GERD. In addition, one leisure sedentary behaviour, such as time spent watching television, was independently and predominately responsible for genetic causal effect on GERD (OR 3.74; 95% CI 2.89 to 4.84; p<0.001). No causal effects of social activities and driving on GERD were observed.

Conclusions

Genetically predicted Townsend Deprivation Index at recruitment and leisure watching television were causally associated with increased risk of GERD, and age at completion of full-time education and average total household income before tax were causally associated with decreased risk of GERD.
ARF1-related disorder: phenotypic and molecular spectrum
Authors: de Sainte Agathe Jean-Madeleine , Pode-Shakked Ben , Naudion Sophie , Michaud Vincent , Arveiler Benoit , Fergelot Patricia , Delmas Jean , Keren Boris , Poirsier Céline , Alkuraya Fowzan S , Tabarki Brahim , Bend Eric , Davis Kellie , Bebin Martina , Thompson Michelle L , Bryant Emily M , Wagner Matias , Hannibal Iris , Lenberg Jerica , Krenn Martin , Wigby Kristen M , Friedman Jennifer R , Iascone Maria , Cereda Anna , Miao Térence , LeGuern Eric , Argilli Emanuela , Sherr Elliott , Caluseriu Oana , Tidwell Timothy , Bayrak-Toydemir Pinar , Hagedorn Caroline , Brugger Melanie , Vill Katharina , Morneau-Jacob Francois-Dominique , Chung Wendy , Weaver Kathryn N , Owens Joshua W , Husami Ammar , Chaudhari Bimal P , Stone Brandon S , Burns Katie , Li Rachel , de Lange Iris M , Biehler Margaux , Ginglinger Emmanuelle , Gérard Bénédicte , Stottmann Rolf W , Trimouille Aurélien
Published: April 2023

Purpose

ARF1was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum ofARF1-related neurodevelopmental disorder.

Methods

We collected detailed phenotypes of an international cohort of individuals (n=17) withARF1variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated.

Results

De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) inARF1were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder.

Conclusion

We confirm the role ofARF1in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration.
Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects
Authors: Wu Haiyin , Huang Zhenquan , Wang Xuan , Chen Mingyu , Chen Wei , Hua Yao , Ren Jian , Shen Luyao , Song Yixuan , Zhou Ying , Luo Chunxia , Lin Yuhui , Wang Yilong , Chang Lei , Li Fei , Zhu Dongya
Published: April 2023

Background

Poststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke. ZL006-05, a dual-target analgesic we developed, dissociates nitric oxide synthase from postsynaptic density-95 while potentiates α2-containing γ-aminobutyric acid type A receptor. This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects.

Methods

Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice. Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride) staining or Nissl staining. Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores. Grid-walking, cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions. Spatial learning was assessed using Morris water maze task. Depression and anxiety were induced by unpredictable chronic mild stress. Depressive behaviours were assessed by tail suspension, forced swim and sucrose preference tests. Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests. Pharmacokinetics, toxicokinetics and long-term toxicity studies were performed in rats.

Results

Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly, with a treatment window of 12 hours after ischemia, and reduced plasminogen activato-induced haemorrhagic transformation. ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice, had antidepressant and anxiolytic effects in stroke mice. ZL006-05 crossed the blood–brain barrier and distributed into the brain rapidly, and had a high safety profile in toxicokinetics and long-term toxicological studies.

Conclusion

ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy, safety and targeting of clinical issues.
Photochemically induced thalamus infarction impairs cognition in a mouse model
Authors: Zhang Chen , Li Shiping , Wang Yongjun , Shi Jiong
Published: April 2023

Background

Small subcortical infarcts account for up to 25% of ischaemic strokes. Thalamus is one of the subcortical structures that commonly manifest with lacunar infarcts on MRI of the brain. Studies have shown that thalamus infarction is associated with cognitive decline. However, due to the lack of proper animal models, little is known about the mechanism. We aimed to establish a focal thalamus infarction model, characterise the infarct lesion and assess functional effects.

Methods

Male C57BL/6J mice were anaesthetised, and Rose Bengal dye was injected through the tail vein. The right thalamus was illuminated with green laser light by stereotactic implantation of optic fibre. Characteristics of the infarct and lesion evolution were evaluated by histological analysis and 7T MRI at various times. The cognitive and neurological functions were assessed by behavioural tests. Retrograde tracing was performed to analyse neural connections.

Results

An ischaemic lesion with small vessel occlusion was observed in the thalamus. It became a small circumscribed infarct with reactive astrocytes accumulated in the infarct periphery on day 21. The mice with thalamic infarction demonstrated impaired learning and memory without significant neurological deficits. Retrogradely labelled neurons in the retrosplenial granular cortex were reduced.

Conclusion

This study established a mouse model of thalamic lacunar infarction that exhibits cognitive impairment. Neural connection dysfunctions may play a potential role in post-stroke cognitive impairment. This model helps to clarify the pathophysiology of post-stroke cognitive impairment and to develop potential therapies.
From color to shape: ontogenetic shifts in traits of the freshwater crab Dilocarcinus pagei (Brachyura: Trichodactylidae)
Authors: da Silva Alexandre R. , Nogueira Caio S.
Published: April 2023

Crustaceans usually undergo a series of changes after the puberty molt. These changes are often associated with size increases in the body and in structures such as the abdomen and claws so that they can achieve higher reproductive fitness. These morphological changes allow the animal to fight, court, and signal for its conspecific with better performance. To compare ontogenetic changes, we used the freshwater crab Dilocarcinus pagei Stimpson, 1851 as a model. We analyzed differences in carapace and claw shape, force generation (via the apodeme area), morphological integration of claws, and color changes among demographic groups. Adult crabs had an increase in claw and carapace size followed by a shape change that makes the claws more robust. In addition, the animals changed from a dark brown coloration in juveniles to a dark red coloration in adult males, while adult females presented a dark red-brown coloration. Presumably, phenotypic changes may enhance crabs’ ability to obtain different food sources, as well as fight for sexual partners, and manipulate females during courtship. Color changes can be a strategy by which adult males can signal to females, while the dark brown coloration of juveniles can help in camouflage in the substrate.
Why Does Volatility Uncertainty Predict Equity Option Returns?
Authors: Cao Jie Jay , Vasquez Aurelio , Xiao Xiao , Zhan Xintong Eunice
Published: April 2023

Delta-hedged option returns consistently decrease in volatility of volatility changes (volatility uncertainty), for both implied and realized volatilities. We provide a thorough investigation of the underlying mechanisms including model-risk and gambling-preference channels. Uncertainty of both volatilities amplifies the model risk, leading to a higher option premium charged by dealers. Volatility of volatility-increases, rather than that of volatility-decreases, contributes to the effect of implied volatility uncertainty, supporting the gambling-preference channel. We further strengthen this channel by examining the effects of option end-users net demand and lottery-like features, and by decomposing implied volatility changes into systematic and idiosyncratic components.
ARKODE: A Flexible IVP Solver Infrastructure for One-step Methods
Authors: Reynolds Daniel R. , Gardner David J. , Woodward Carol S. , Chinomona Rujeko
Published: April 2023

We describe the ARKODE library of one-step time integration methods for ordinary differential equation (ODE) initial-value problems (IVPs). In addition to providing standard explicit and diagonally implicit Runge–Kutta methods, ARKODE supports one-step methods designed to treat additive splittings of the IVP, including implicit-explicit (ImEx) additive Runge–Kutta methods and multirate infinitesimal (MRI) methods. We present the role of ARKODE within the SUNDIALS suite of time integration and nonlinear solver libraries, the core ARKODE infrastructure for utilities common to large classes of one-step methods, as well as its use of “time stepper” modules enabling easy incorporation of novel algorithms into the library. Numerical results show example problems of increasing complexity, highlighting the algorithmic flexibility afforded through this infrastructure, and include a larger multiphysics application leveraging multiple algorithmic features from ARKODE and SUNDIALS.
Modelling Water Transport Limitations and Ionic Voltage Losses in Bipolar Membrane Water Electrolysis
Authors: Weiland Oskar , Trinke Patrick , Bensmann Boris , Hanke-Rauschenbach Richard
Published: April 2023

This work analyses the water transport and ionic losses in bipolar membranes at water electrolysis cells conditions. In common bipolar setups, water is split at the bipolar interface between the anion exchange membrane (AEM) and the cation exchange membrane (CEM). Accordingly, ions (protons and hydroxide ions) are transported to the electrodes, carrying the water out of both membranes via electro-osmotic drag. These outfluxes plus the required water amount for the splitting process have to be compensated by water diffusion towards the bipolar interface. The effect of water transport on the polarisation behaviour is additionally shown. Mayerhöfer et al. [ACS Appl. Energy Mater.,
3, 9635 (2020)] and Oener et al.[ACS Energy Lett.,
6, 1 (2021)] decreased polarization losses and increased the current density range by reducing either the AEM or the CEM thickness, respectively. Our model validates these improvements by calculating the limiting current density caused by dehydration of the membranes. Further analysis shows that thinner AEM thicknesses decrease membrane voltage losses more than thinner CEM due to lower ionic conductivities and faster dehydration of AEMs. Thin CEMs on the other hand, are more efficient at increasing the limiting current density.
Electro- and Photocatalytic Conversion of N2 to NH3 by Chemically Modified Transition Metal Dichalcogenides, MoS2, and WS2
Authors: Ganesan Ashwin , Alhowity Samar , Alsaleh Ajyal Z. , Guragain Manan , Omolere Olatomide , Cundari Thomas R. , Kelber Jeffry , D’Souza Francis
Published: April 2023

Electro- and photocatalytic reduction of N2 to NH3—the nitrogen reduction reaction (NRR)—is an environmentally- and energy-friendly alternative to the Haber-Bosch process for ammonia production. There is a great demand for the development of novel semiconductor-based electrocatalysts with high efficiency and stability for the direct conversion of inert substrates—including N2 to ammonia—using visible light irradiation under ambient conditions. Herein we report electro-, and photocatalytic NRR with transition metal dichalcogenides (TMDCs), viz MoS2 and WS2. Improved acid treatment of bulk TMDCs yields exfoliated TMDCs (exTMDCs) only a few layers thick with ∼10% S vacancies. Linear scan voltammograms on exMoS2 and exWS2 electrodes reveal significant NRR activity for exTMDC-modified electrodes, which is greatly enhanced by visible light illumination. Spectral measurements confirm ammonia as the main reaction product of electrocatalytic and photocatalytic NRR, and the absence of hydrazine byproduct. Femtosecond-resolved transient absorption studies provide direct evidence of interaction between photo-generated excitons/trions with N2 adsorbed at S vacancies. DFT calculations corroborate N2 binding to exMoS2 at S-vacancies, with substantial π-backbonding to activate dinitrogen. Our findings suggest that chemically functionalized exTMDC materials could fulfill the need for highly-desired, inexpensive catalysts for the sustainable production of NH3 using Sunlight under neutral pH conditions without appreciable competing production of H2.
LT-LiNi1/3Mn1/3Co1/3O2: A Partially-Disordered, Composite Rock Salt Cathode Prepared by Flame Spray Pyrolysis for Li-Ion Batteries
Authors: Ku Kyojin , Han Jinhyup , Li Linze , Gim Jihyeon , Park Jehee , Shi Boyu , Liang Yujia , Stark Anthony , Wang Chongmin , Croy Jason R. , Thackeray Michael M. , Libera Joseph , Lee Eungje
Published: April 2023

A unique composite cathode structure for Li-ion batteries, designated LT-LiNi1/3Mn1/3Co1/3O2 (or LT-NMC111), has been prepared by flame spray pyrolysis and subsequent annealing between 400 and 650 °C. It is composed predominantly of structurally-integrated and partially-disordered lithiated-spinel and layered components, both of which can be broadly described as partially-disordered rock salt constituents. The paper describes the evolution of the LT-NMC111 structure as a function of the synthesis method, annealing temperature, and electrochemical properties in the context of other recently reported “low-temperature” (LT) materials, such as LT-LiCo1−xAlxO2 and LT-LiMn0.5Ni0.5O2 or, in spinel notation, LT-Li2Co2–2xAl2xO4 and LT-Li2MnNiO4, respectively.
Length-Weight Relationships of Twenty-Nine Native Fish Species from Hongshui River, Southern China
Authors: He Jiayang , Wu Zhiqiang , Huang Liangliang , Li Yusen , Sun Yangyan , Wang Dongjie , Feng Jie , Lin Yong , He Anyou
Published: April 2023

Twenty-nine native freshwater fish species belonging to the four orders and eight families were collected from the Hongshui River, which belongs to the upper reaches of the Pearl River, to analyze their length-weight relationships (LWRs). Twenty-nine freshwater native fish were sourced using cages (0.2 m in height, 0.25 m in width, and 8 m in length, with a mesh size of 5 mm) and triple gillnets (20–40 m long, 1–3 m high, and mesh size, 2−3 cm) between December 2021 and July 2022. For each freshwater fish, the total length (TL) and weight were measured to the nearest 1.0 mm and 0.1 g. All LWR parameters of the twenty-nine species were statistically significant

P
<
0.001

. The length-weight relationships for the nine species were new to the FishBase and new maximum lengths were recorded for the twenty species. The LWR values provided for the first time will help to validate the accuracy and predictability of the Bayesian models for estimating the species-specific growth parameters of the data-poor species.
Evaluating Pore Structure of Shale Reservoirs through Pore Space Multifractal Characterization
Authors: Dai Quanqi , He Yingfu , Zheng Da , Zhu Yangwen , Wang Rui , Yu Hongmin , Zhou Yinbang , Wang Guiwen , Li Yafeng , Wu Hao
Published: April 2023

Characteristics of pore structure are crucial to oil exploration and development in shale reservoirs, but practical evaluation of shale pore structure remains a longstanding challenge. In this study, based on nuclear magnetic resonance transverse relaxation time (T2) spectra under water-saturated and irreducible conditions, total pore space and moveable fluid space were skillfully determined. Meanwhile, multifractal spectra were used to characterize T2 distributions of total pore space and movable fluid space. The results show characteristic parameters of high probability measure areas of multifractal spectra (multifractal parameters) have strong negative correlations with T2 geometric mean value, and average radii of pore and throat increase with a decrease in the multifractal parameters, indicating the shale reservoirs with low values of the multifractal parameters may have good pore structure. Moreover, clay mineral content has strong positive effects on the multifractal parameters. In contrast, (quartz+feldspar) mineral content negatively influences on the multifractal parameters. Finally, new accurate models for permeability estimation in core scale and well-logging scale of shales are both proposed based on the multifractal parameters, which are also applicable for the other reservoirs. Overall, this study is important and timely for evaluating pore structure and predicting permeability in shale reservoirs.
Porous Media Model of Reservoir considering Seepage Stress Coupling and Seepage Field Analysis
Authors: Wang Xu , Jia Zhenzhen
Published: April 2023

In the process of reservoir exploitation, the range of rock stress field changes is much larger than the reservoir area where the seepage occurs; so the amount of calculation of the existing seepage stress full coupling method is often very huge. Based on the theory of seepage mechanics and rock mechanics, a coupling analysis model of reservoir multiphase seepage and stress is established, and a numerical solution is established by using finite element and finite difference methods. The evolution law of the seepage field and stress field and the change of rock mechanics parameters can be studied, with emphasis on the readjustment of rock stress distribution and its deformation characteristics under the influence of the seepage field. At the same time, to improve the calculation efficiency of numerical simulation, considering the difference between the seepage calculation area and stress calculation area, the finite element method is improved. The percolation area of the reservoir is calculated with a fine grid to obtain a more accurate distribution of underground fluid. The coarse grid is used to calculate the stress calculation area and to reduce the calculation time. The mechanical equilibrium equation in the fully coupled theory is discretized on the coarse grid by the finite element method. The mass conservation equation is discretized on the fine grid by the finite volume method. The numerical simulation of Terzaghi’s one-dimensional consolidation problem and Mandel’s two-dimensional consolidation problem shows that the calculation results of this method are in good agreement with the analytical solution. Through the numerical calculation of a two-dimensional single-phase flow single well production problem and a three-dimensional two-phase flow five-point well pattern production problem, the influence of the seepage stress coupling effect in reservoir numerical simulation is analyzed.
Immune Cell Response during COVID-19 Infection and following SARS-CoV-2 Vaccination in Patients Admitted to Intensive Care Unit
Authors: Bahrini Khadija , Stambouli Nejla , Ben Azaiez Mouna , Rebai Aicha , Abid Ferid , Romdhani Chihebeddine , Labben Iheb , Gharsallah Hédi , Ferjani Mustapha
Published: April 2023

Background. Immune response plays a crucial role in virus clearance during COVID-19 infection and underpins vaccine efficacy. Herein, we aimed to assess the immune response during COVID-19 infection and following SARS-CoV-2 vaccination. Methods. In this retrospective study, 94 confirmed COVID-19 patients admitted to the intensive care unit were categorized into unvaccinated patients (n = 50), including 33 deceased and 17 discharged patients, and vaccinated group (n = 44) with 26 deceased and 18 discharged patients. Records of patients with severe COVID-19 admitted to the ICU between March, 2021 and March, 2022 were gathered and analyzed. Result. The assessment of immune cell counts revealed a large rise of neutrophils associated to decrease number of lymphocytes in patients with COVID-19 infection. In dead patients, we detected a significant correlation between neutrophils and inflammatory parameters such as IL-6 and CRP. Moreover, analysis of immune cell count following vaccination did not reveal any significant difference. However, the most substantial result, herein, detected is the decrease level of IL-6 in vaccinated patients as compared to unvaccinated. The reduce level of IL-6 following vaccination is observed in discharged patients as compared to deceased. Regarding the level of mortality after vaccination, we showed that all patients who received the first dose were died (46.1%, n = 12) as compared to those who have received two doses (34.6%, n = 9) and the third dose of vaccine (19.23%, n = 3) (

p
=
0.0018

). Strikingly, studying the inflammatory parameters after each vaccine dose, we revealed a significant decrease of IL-6 level after the booster dose (third dose), especially in vaccinated discharged patients. Conclusions. Neutrophils combined with IL-6 and CRP can be very useful markers to predict disease severity in patients admitted to ICU. The decrease level of IL-6 in vaccinated group pointed out the impact of vaccination to prevent inflammatory cytokine release.
Inhibition of the SARS-CoV-2 Main Protease by Isoquercitrin γ-Cyclodextrin Inclusion Complex Formulations: A Biochemical and In Silico Study
Authors: Wurtele Martin , Coelho Camila , Gallo Gloria , Campos Claudia , Hardy Leon , Perez Castillo Yunierkis , Moriwaki Masamitsu , Kapoor Mahendra P. , de Sousa Damião Pergentino
Published: April 2023

The main protease (Mpro) of SARS-CoV-2 is a well-established drug target for rational drug design of COVID-19 inhibitors. To address the serious challenge of COVID-19, we have performed biochemical inhibition screens with recombinantly expressed SARS-CoV-2 main protease (Mpro). A fluorescent assay was used to identify the flavonoid isoquercitrin as an Mpro inhibitor. Both isoquercitrin encapsulated in γ-cyclodextrin (inclusion complex formulations) and alone inhibited SARS-CoV-2 Mpro. For isoquercitrin, a Ki value of 32 μM (IC50 = 63 μM) was obtained. Isoquercitrin γ-cyclodextrin inclusion complex formulations additionally inhibited Zika virus NS2B-NS3pro leading to an IC50 value of 98 μM. Formulations containing the other flavonoid compounds diosmetin-7-O-glucoside, hesperetin-7-O-glucoside, and naringenin-7-O-glucoside did not inhibit SARS-CoV-2 Mpro. Steady-state kinetics indicate that the inhibition mechanism of Mpro by isoquercitrin is potentially competitive. Molecular modeling studies carried out with MM/PBSA confirm the likely modes of isoquercitrin binding to both proteases. These modeling results can be used in the development of structural analogs of isoquercitrin with better inhibitory profiles and potential candidates for anti-coronavirus drugs. Since the targeted proteases are essential for viral activity, the delivery isoquercitrin-cyclodextrin inclusion complex formulations could be of great interest for the development of future antiviral drugs to target intracellular virus proteins or other components.
A Lifetime of Play: Group Medical Clowning with Older Adults
Authors: Korin Orly , Babis Deby , Ben-Shalom Uzi , Gruber Alejandro Alex
Published: April 2023

Play is fundamental to a person’s well-being. However, cultural norms and ageism have negatively impacted this practice among older adults. This study explored to what extent medical clowning promotes play among older adults. Qualitative data were collected in weekly group sessions of medical clowning in an Israeli retirement home. Group medical clowning offered participants a new sort of playground, which combined body play, cognitive play, and role-play. The clown created an ambience that legitimized older adults’ loosening-up, expanding their space, feeling happy, and developing new creative interactions. He enabled participants to get involved in free play, thus freeing them of social constructions regarding older adults. The medical clown created a community of play and legitimized play among older adults, thereby breaking rules based on social stereotypes, the convention that older adults should not behave nonsensically and challenging the accepted social norms of the retirement home.
Observations of Agonistic Behavior between Two Male Gobies Acentrogobius virgatulus (Jordan & Snyder, 1901), in Maizuru Bay, Kyoto Prefecture, Japan
Authors: Godfrey Hunter Harter , Henmi Yumi
Published: April 2023

Acentrogobius virgatulus (Jordan & Snyder, 1901) is a small coastal species of goby found along the Western Pacific. It is commonly found in Maizuru bay along the muddy sediment between the intertidal zone and depths of 10 m. In June and July of 2022, two independent agonistic interactions between male A. virgatulus were observed and recorded during its spawning season. One interaction, lasting over 4 minutes, included certain aggressive behaviors such as jaw locking, mouth gaping, fin extensions, rapid color changes, and fast strikes to the head and body. Another interaction exhibited similar mouth gaping, fin extension, and rapid color changes but did not lead to further escalation. These behaviors coincide with those found in similar species and provides in situ evidence of these uncommon interactions. This is the first record of agonistic behavior by an Acentrogobius species. Accumulating findings such as these can contextualize intraspecific interactions, reveal differences across multiple species, and guide future experiments.
Supplementary Table S4 from SALVO: Single-Arm Trial of Ipilimumab and Nivolumab as Adjuvant Therapy for Resected Mucosal Melanoma
Authors: Kottschade Lisa A. , Pond Gregory Russell , Olszanski Anthony J. , Zakharia Yousef , Domingo-Musibay Evidio , Hauke Ralph J. , Curti Brendan D. , Schober Sarah , Milhem Mohammed M. , Block Matthew Stephen , Hieken Tina , McWilliams Robert R.
Published: April 2023

Outcomes by Subgroups of Primary Site, Adjuvant Radiation, and R0/R1 Resection Margin Status
Supplementary Table S1 from An Immune-Related Gene Expression Signature Predicts Benefit from Adding Atezolizumab to FOLFOXIRI plus Bevacizumab in Metastatic Colorectal Cancer
Authors: Antoniotti Carlotta , Boccaccino Alessandra , Seitz Robert , Giordano Mirella , Catteau Aurélie , Rossini Daniele , Pietrantonio Filippo , Salvatore Lisa , McGregor Kimberly , Bergamo Francesca , Conca Veronica , Leonetti Simone , Morano Federica , Papiani Giorgio , Tamburini Emiliano , Bensi Maria , Murgioni Sabina , Ross Douglas Teller , Passardi Alessandro , Boquet Isabelle , Nielsen Tyler J. , Galon Jérôme , Varga Matthew Gordon , Schweitzer Brock L. , Cremolini Chiara
Published: April 2023

Baseline characteristics of patients according to the predefined and optimized DetermaIO score positivity cut-point in the pMMR tumours group.
Data from Somatic Exonic Deletions in RUNX1 Constitutes a Novel Recurrent Genomic Abnormality in Acute Myeloid Leukemia
Authors: Eriksson Anna , Engvall Marie , Mathot Lucy , Österroos Albin , Rippin Martin , Cavelier Lucia , Ladenvall Claes , Baliakas Panagiotis
Published: April 2023

AbstractPurpose:
In acute myeloid leukemia (AML), somatic mutations (commonly missense, nonsense, and frameshift indels) in RUNX1 are associated with a dismal clinical outcome. Inherited RUNX1 mutations cause familial platelet disorder. As approximately 5%–10% of germline RUNX1 mutations are large exonic deletions, we hypothesized that such exonic RUNX1 aberrations may also be acquired during the development of AML.
Experimental Design:
Sixty patients with well-characterized AML were analyzed with multiplex ligation-dependent probe amplification (n = 60), microarray (n = 11), and/or whole-genome sequencing (n = 8).
Results:
In total, 25 (42% of the cohort) RUNX1-aberrant patients (defined by the presence of classical mutations and/or exonic deletions) were identified. Sixteen patients (27%) carried only exonic deletions, 5 (8%) carried classical mutations, and 4 (7%) carried both exonic deletions and mutations. No significant difference was observed between patients with classical RUNX1 mutations and RUNX1 exonic deletions in median overall survival (OS, 53.1 vs. 38.8 months, respectively, P = 0.63). When applying the European Leukemia Net (ELN) classification including the RUNX1-aberrant group, 20% of the patients initially stratified as intermediate-risk (5% of the whole cohort) were reassigned to the high-risk group, which improved the performance of ELN classification regarding OS between intermediate- and high-risk groups (18.9 vs. 9.6 months, P = 0.09).
Conclusions:
Somatic RUNX1 exonic deletions constitute a novel recurrent aberration in AML. Our findings have important clinical implications regarding AML classification, risk stratification, and treatment decision. Moreover, they argue in favor of further investigating such genomic aberrations not only in RUNX1 but also in other genes implicated in cancer biology and management.
Supplementary Tables S1-S11 from Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer
Authors: Pradat Yoann , Viot Julien , Yurchenko Andrey A. , Gunbin Konstantin , Cerbone Luigi , Deloger Marc , Grisay Guillaume , Verlingue Loic , Scott Véronique , Padioleau Ismael , Panunzi Leonardo , Michiels Stefan , Hollebecque Antoine , Jules-Clément Gérôme , Mezquita Laura , Lainé Antoine , Loriot Yohann , Besse Benjamin , Friboulet Luc , André Fabrice , Cournède Paul-Henry , Gautheret Daniel , Nikolaev Sergey I.
Published: April 2023

These tables present clinical data, sample data, whole-exome and transcriptome sequencing results, literature references, and external data sources that were used for the analyses presented in the main text.
Supplementary Figures S1-S24 from Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer
Authors: Pradat Yoann , Viot Julien , Yurchenko Andrey A. , Gunbin Konstantin , Cerbone Luigi , Deloger Marc , Grisay Guillaume , Verlingue Loic , Scott Véronique , Padioleau Ismael , Panunzi Leonardo , Michiels Stefan , Hollebecque Antoine , Jules-Clément Gérôme , Mezquita Laura , Lainé Antoine , Loriot Yohann , Besse Benjamin , Friboulet Luc , André Fabrice , Cournède Paul-Henry , Gautheret Daniel , Nikolaev Sergey I.
Published: April 2023

These figures provide complementary informationfor the figures presented in the main text and illustrations of the methods section.
Supplemental Figure S7 from Reprogramming Cancer into Antigen-Presenting Cells as a Novel Immunotherapy
Authors: Linde Miles H. , Fan Amy C. , Köhnke Thomas , Trotman-Grant Aaron C. , Gurev Sarah F. , Phan Paul , Zhao Feifei , Haddock Naomi L. , Nuno Kevin A. , Gars Eric J. , Stafford Melissa , Marshall Payton L. , Dove Christopher G. , Linde Ian L. , Landberg Niklas , Miller Lindsay P. , Majzner Robbie G. , Zhang Tian Yi , Majeti Ravindra
Published: April 2023

Benchmarking antigen presentation by TR-APCs