bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a Context-Bound Model for Hospital Triage in Disasters and Mass Casualty Incidents in the Health System of Iran
Authors: Bazyar Jafar , Farrokhi Mehrdad , Salari Amir , Noroozi Mehdi , Khankeh Hamidreza
Published: June 2021

Objective:

The aim of this study was to develop a context-bound model of hospital triage in disasters and mass casualty incidents in the health system of Iran.

Methods:

This study was done using a sequential mixed method. Data were analyzed using Expert Choice software program.

Results:

In the qualitative phase, 27 specialists were interviewed. Walking and purposeful movement, airway and respiration, circulatory status, and mental indices were included in the finalized model. In the quantitative phase, 21 participants responded to a questionnaire for weighting and ranking the final indices based on 3 competing options, including clinical importance of the index, lack of complexity and simplicity in implementation, and speed of implementation. The index of walking and purposeful movements weighing 0.300 and ranking 1, airway and respiration weighing 0.276 and ranking 2, blood circulatory status weighing 0.245 and ranking 3, and finally mental status weighing 0.179 and ranking 4 were obtained.

Conclusions:

This is the first attempt to design and develop a new context-bound model of hospital triage in disasters and mass casualties in Iran. The development of new triage models is a dynamic and continuous process, and changes will be applied to them, in case further developments and improvements are required.
Self-Medication in the COVID-19 Pandemic: Survival of the Fittest
Authors: Rafiq Kiran , Nesar Shagufta , Anser Humaira , Leghari Qurat-ul-Ain , Hassan Alisha , Rizvi Alina , Raza Aleeza , Saify Zafar Saied
Published: June 2021

Objective:

After the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic, intense efforts to combat the novel coronavirus were undertaken, with many fatalities in most regions of the world. The high fatality rate and socioeconomic collapse affected the health of uninfected individuals because healthcare measures and scheduled clinical and hospital visits were avoided by people in an attempt to reduce their exposure to the contagion. The general population began self-medication practices as means to safeguard against exposure to the virus.

Methods:

The present study investigated the effectiveness of self-medication compliance among the general population. For this purpose, a questionnaire on the Zenodo scale was developed and adults and teen respondents were asked to complete it, after providing consent. The data gathered were analyzed using IBM SPSS Statistics Version 26.

Results:

The study amazingly found high compliance with self-medication among the focused population during the period of COVID-19. Estimated results showed a highly significant correlation of 0.000, P < 0.05, between the adaptation of self-medication and pandemic situation, which was estimated from chi-squared and Fisher test results.

Conclusions:

However, the fear of coronavirus made the practice, or malpractice, a survival of the fittest, innate ability of human nature.
Importance of Pharmacy Partnerships in Effective COVID-19 Vaccine Distribution
Authors: Pammal Rajkumar S. , Kreinces Jason B. , Pohlman Kevin L.
Published: June 2021

The goal of vaccinating the majority of Americans against coronavirus disease 2019 (COVID-19) in a timely manner requires a robust federal vaccine distribution plan involving pharmacy partnerships. Previously, the 2009 Centers for Disease Control and Prevention (CDC) H1N1 Vaccine Pharmacy Initiative resulted in approximately 10% of adults who received a vaccine during the 2009 pandemic reporting they were vaccinated at a pharmacy. This proportion has already largely increased for COVID-19 vaccinations, with the US Department of Health and Human Services (HHS) using similar channels for vaccination as existing partnerships with national pharmacy and grocery retail chains for the COVID-19 Community-Based Testing Program. It continues to prove crucial that the Biden administration’s national COVID-19 vaccine distribution plan, including the Federal Retail Pharmacy Program, focus on ensuring equitable vaccine distribution and access in medically underserved areas and to vulnerable populations, enabling maximum uptake of COVID-19 vaccines.
COVID-19: A Comprehensive Analysis of the Pandemic’s Effect on an Emergency Department
Authors: Flamm Avram , Lee Alexander , Mencl Francis
Published: June 2021

Objective:

Coronavirus disease 2019 (COVID-19, caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is a historic pandemic severely impacting health care. This study examines its early effect on a busy academic emergency department.

Methods:

A retrospective analysis of patients from an academic tertiary care Level I trauma, cardiac and stroke center’s emergency department seeing an average of 54,000 adults and 21,000 pediatric patients per year. Total visits, reasons for patient visits, demographics, disposition, and length of stay were analyzed from January through July 2020 and compared with the same time period in the previous 2 y.

Results:

From March through July 2020 there were statistically significant decreases in the total number of patient visits (-47%) especially among pediatric (-73%) and elderly (-43%) patients and those with cardiovascular (-39%), neurological (-63%) complaints, headaches (-60%), back pain (-64%), abdominal pain (-51%), and minor trauma (-71%). There was, however, a significant increase in pulmonary complaints (+54%), as well as admissions (+32%), and length of stay (+40%).

Conclusions:

There was a significant drop in overall patients and select groups early in the pandemic, while admissions and emergency department length of stay both increased. This has implications for future pandemic planning.
The Usefulness of Shock Index and Modified Shock Index in Predicting the Outcome of COVID-19 Patients
Authors: Kurt Erdem , Bahadirli Suphi
Published: June 2021

Objective:

The aim of this study is to investigate the accuracy of shock index (SI) and modified shock index (mSI) in predicting the intensive care unit (ICU) requirement and in-hospital mortality among coronavirus disease (COVID-19) patients who are admitted to the emergency department (ED). Likewise, the effects of patients’ conditions such as age, gender, and comorbidity on prognosis will be analyzed.

Methods:

The files were retrospectively scanned for all COVID-19 patients over the age of 18 years who were admitted to the ED and hospitalized between January 1, 2021, and March 15, 2021. The area under the receiver operating characteristic curve and the area under the curve (AUC) were used to assess each scoring system discriminatory for predicting in-hospital mortality and ICU admission.

Results:

There were 464 patients included in this study. The mean age of the patients was 62.4 ± 16.7, of which 245 were men and 219 were women. The most common comorbidity in patients was hypertension (200; 43.1%), followed by chronic obstructive pulmonary disease (174; 37.5%), and coronary artery disease (154; 33.2%). In terms of in-hospital mortality, the AUC of SI, and mSI were 0.719 and 0.739, respectively. In terms of an ICU requirement, the AUC of SI, and mSI were 0.704 and 0.729, respectively.

Conclusion:

In this study, it was concluded that SI and mSI are useful in predicting in-hospital mortality and ICU requirement in COVID-19 patients. In addition, another important result of the study is that advanced age, male gender, and hypertension may be associated with a poor prognosis.
Two Sources for Abu Dhuʾayb al-Hudhali's Famous Elegy
Authors: Hussein Ali Ahmad
Published: June 2021

This article considers the celebrated elegy by the classical 7th-century Arabic poet, Abu Dhuʾayb al-Hudhali — his ʿayniyya, which ends with ʿayn as a rhyming letter. Analyzing the poem's structure and comparing it with that of two poems composed by Abu Dhuʾayb's teacher, Saʿida b. Juʾayya al-Hudhali, leads to the conclusion that Saʿida's two poems were the main sources on which the pupil drew to create his poem. The sophisticated changes that Abu Dhuʾayb introduced in structure and content, however, made his poem more memorable than those of his teacher. The article raises another question, to which there is, as yet, no definitive answer: what was the true inspiration for Abu Dhuʾayb's poem? Was it the death of his sons, as is traditionally believed, or was it literary: to surpass his teacher in composing a more skillful poem?
Pandemics and Political Development
Authors: Gingerich Daniel W. , Vogler Jan P.
Published: June 2021

Do pandemics have lasting consequences for political behavior? The authors address this question by examining the consequences of the deadliest pandemic of the last millennium: the Black Death (1347–1351). They claim that pandemics can influence politics in the long run if the loss of life is high enough to increase the price of labor relative to other factors of production. When this occurs, labor-repressive regimes, such as serfdom, become untenable, which ultimately leads to the development of proto-democratic institutions and associated political cultures that shape modalities of political engagement for generations. The authors test their theory by tracing the consequences of the Black Death in German-speaking Central Europe. They find that areas hit hardest by that pandemic were more likely to adopt inclusive political institutions and equitable land ownership patterns, to exhibit electoral behavior indicating independence from landed elite influence during the transition to mass politics, and to have significantly lower vote shares for Hitler’s National Socialist Party in the Weimar Republic’s fateful 1930 and July 1932 elections.
Consistency analysis of global positioning system position errors with typical statistical distributions
Authors: Specht Mariusz
Published: June 2021

Research into statistical distributions ofφ,λand two-dimensional (2D) position errors of the global positioning system (GPS) enables the evaluation of its accuracy. Based on this, the navigation applications in which the positioning system can be used are determined. However, studies of GPS accuracy indicate that the empiricalφandλerrors deviate from the typical normal distribution, significantly affecting the statistical distribution of 2D position errors. Therefore, determining the actual statistical distributions of position errors (1D and 2D) is decisive for the precision of calculating the actual accuracy of the GPS system. In this paper, based on two measurement sessions (900,000 and 237,000 fixes), the distributions of GPS position error statistics in both 1D and 2D space are analysed. Statistical distribution measures are determined using statistical tests, the hypothesis on the normal distribution ofφandλerrors is verified, and the consistency of GPS position errors with commonly used statistical distributions is assessed together with finding the best fit. Research has shown thatφandλerrors for the GPS system are normally distributed. It is proven thatφandλerrors are more concentrated around the central value than in a typical normal distribution (positive kurtosis) with a low value of asymmetry. Moreover,φerrors are clearly more concentrated thanλerrors. This results in larger standard deviation values forφerrors thanλerrors. The differences in both values were 25–39%. Regarding the 2D position error, it should be noted that the value of twice the distance root mean square (2DRMS) is about 10–14% greater than the value of R95. In addition, studies show that statistical distributions such as beta, gamma, lognormal and Weibull are the best fit for 2D position errors in the GPS system.
Improved diagnosis of SARS-CoV-2 by using nucleoprotein and spike protein fragment 2 in quantitative dual ELISA tests
Authors: De Marco Verissimo Carolina , O'Brien Carol , López Corrales Jesús , Dorey Amber , Cwiklinski Krystyna , Lalor Richard , Doyle Jack M. , Field Stephen , Masterson Claire , Ribes Martinez Eduardo , Hughes Gerry , Bergin Colm , Walshe Kieran , McNicholas Bairbre , Laffey John G. , Dalton John P. , Kerr Colm , Doyle Sean
Published: June 2021

The novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative enzyme-linked immunosorbent assays (ELISAs) that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive coronavirus disease-2019 (COVID-19) cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients who had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.
Atom Probe Analysis of Nanoparticles Through Pick and Coat Sample Preparation
Authors: Josten Jan P , Felfer Peter J
Published: June 2021

The ability to analyze nanoparticles in the atom probe has often been limited by the complexity of the sample preparation. In this work, we present a method to lift–out single nanoparticles in the scanning electron microscope. First, nanoparticles are dispersed on a lacey carbon grid, then positioned on a sharp substrate tip and coated on all sides with a metallic matrix by physical vapor deposition. Compositional and structural insights are provided for spherical gold nanoparticles and a segregation of silver and copper in silver copper oxide nanorods is shown in 3D atom maps. Using the standard atom probe reconstruction algorithm, data quality is limited by typical standard reconstruction artifacts for heterogeneous specimens (trajectory aberrations) and the choice of suitable coatings for the particles. This approach can be applied to various unsupported free-standing nanoparticles, enables preselection of particles via correlative techniques, and reliably produces well-defined structured samples. The only prerequisite is that the nanoparticles must be large enough to be manipulated, which was done for sizes down to ~50 nm.
Traumatic events and psychotic experiences: a nationally representative study in Thailand
Authors: Kilian C. , Supanya S. , Probst C. , Morgan C. , Bärnighausen T. , Kittirattanapaiboon P. , Kwansanit P. , Reininghaus U. ,   for the Thai Mental Health Survey Working Group
Published: June 2021

Aims

Most research exploring the link between traumatic events and psychotic experiences has focused on either Australia, Europe or North America. In this study, we expand the existing knowledge to Thailand and investigate the impact of the type and the number of traumatic events on psychotic experiences in Thailand.

Methods

We used data from the nationally representative 2013 Thai National Mental Health Survey (TNMHS), including questions on traumatic events and psychotic experiences. We regressed the lifetime experience of hallucinations or delusions against the following independent variables: the experience of any traumatic event during lifetime (dichotomous; hypothesis 1); the experience of either no traumatic event, one interpersonal, one unintentional or both interpersonal and unintentional traumatic events (categorical; hypothesis 2) and the number of traumatic events experienced during lifetime (categorical; hypothesis 3). We adjusted the regression models for sociodemographic indicators and psychiatric disorders, and considered survey weights.

Results

About 6% (95% confidence interval: 4.9–7.0) of the respondents stated that they had either hallucinatory or delusional experiences during their lifetime. The risk of reporting such experiences was more than doubled as high among respondents who had experienced at least one traumatic event during their lifetime than among those who had not yet experienced one, with higher risks for interpersonal or multiple traumatic events. Our results further indicated an increase in the risk of psychotic experiences as the number of traumatic events increased, with up to an eight-fold higher risk for people exposed to five or more traumatic events in their lifetime, compared to those with no traumatic events.

Conclusions

Individuals reporting interpersonal or multiple traumatic events face much higher risk of psychotic experiences. Effective and widely accessible secondary prevention programmes for people having experienced interpersonal or multiple traumatic events constitute a key intervention option.
Psychopathic Traits, Academic Fraud, and the Mediating Role of Motivation, Opportunity, Rationalization and Perceived Capability
Authors: Dias-Oliveira Eva , Morais Catarina , Pasion Rita
Published: June 2021

Abstract. This study provides initial insights on the relation between psychopathic traits (disinhibition, meanness, and boldness) and academic fraud (prevalence and severity), while considering important mediators of fraud (perceived capability, opportunity, motivation, and rationalization). Based on a large sample of university students ( N = 967), two structural equation models (test and replication) were built to test the study’s main hypothesis and probe the robustness of the results. A direct link from disinhibition to prevalence was found, suggesting that disinhibition is associated with social deviance in the academic context. Higher motivation for cheating exclusively mediated this path. In meanness, rationalization explained lower rates of perceived severity of academic fraud, indicating that cognitive self-justifications trigger dishonest behavior in meanness. Boldness explained the prevalence of academic fraud via perceived capability, suggesting that low-fear, although adaptive in evaluation contexts, may increase the perceived capability for cheating. The reported significant associations support that academic fraud is part of the nomological network of psychopathy and unveil the complexity of the phenomenon.
Evaluation of the Drivers Responsible for Flooding in Africa
Authors: Tramblay Yves , Villarini Gabriele , El Khalki El Mahdi , Gründemann Gaby , Hughes Denis
Published: June 2021

Africa is severely affected by floods, with an increasing vulnerability to these events in the most recent decades. Our improved preparation against and response to this hazard would benefit from an enhanced understanding of the physical processes at play. Here, a database of 399 African stream gauges is used to analyze the seasonality of observed annual maximum flood, precipitation and soil moisture between 1981 and 2018. The database includes a total of 11,302 flood events, covering most African regions. The analysis is based on directional statistics to compare the annual maximum river flood with annual maximum rainfall and soil moisture. The results show that the annual maximum flood in most areas is more strongly linked to the annual peak of soil moisture than of annual maximum precipitation. In addition, the interannual variability of flood magnitudes is better explained by the variability of annual maximum soil moisture than by the variability in the annual maximum precipitation. These results have important implications for flood forecasting and the analysis of the long‐term evolution of these hydrological hazards in relation with their drivers.
Using Mendelian Randomisation methods to understand whether diurnal preference is causally related to mental health
Authors: O’Loughlin Jessica , Casanova Francesco , Jones Samuel E. , Hagenaars Saskia P. , Beaumont Robin N. , Freathy Rachel M. , Watkins Edward R. , Vetter Céline , Rutter Martin K. , Cain Sean W. , Phillips Andrew J. K. , Windred Daniel P. , Wood Andrew R. , Weedon Michael N. , Tyrrell Jessica
Published: June 2021

Late diurnal preference has been linked to poorer mental health outcomes, but the understanding of the causal role of diurnal preference on mental health and wellbeing is currently limited. Late diurnal preference is often associated with circadian misalignment (a mismatch between the timing of the endogenous circadian system and behavioural rhythms), so that evening people live more frequently against their internal clock. This study aims to quantify the causal contribution of diurnal preference on mental health outcomes, including anxiety, depression and general wellbeing and test the hypothesis that more misaligned individuals have poorer mental health and wellbeing using an actigraphy-based measure of circadian misalignment. Multiple Mendelian Randomisation (MR) approaches were used to test causal pathways between diurnal preference and seven well-validated mental health and wellbeing outcomes in up to 451,025 individuals. In addition, observational analyses tested the association between a novel, objective measure of behavioural misalignment (Composite Phase Deviation, CPD) and seven mental health and wellbeing outcomes. Using genetic instruments identified in the largest GWAS for diurnal preference, we provide robust evidence that early diurnal preference is protective for depression and improves wellbeing. For example, using one-sample MR, a twofold higher genetic liability of morningness was associated with lower odds of depressive symptoms (OR: 0.92, 95% CI: 0.88, 0.97). It is possible that behavioural factors including circadian misalignment may contribute in the chronotype depression relationship, but further work is needed to confirm these findings.
Transglutaminase 2 promotes tumorigenicity of colon cancer cells by inactivation of the tumor suppressor p53
Authors: Malkomes Patrizia , Lunger Ilaria , Oppermann Elsie , Abou-El-Ardat Khalil , Oellerich Thomas , Günther Stefan , Canbulat Can , Bothur Sabrina , Schnütgen Frank , Yu Weijia , Wingert Susanne , Haetscher Nadine , Catapano Claudia , Dietz Marina S. , Heilemann Mike , Kvasnicka Hans-Michael , Holzer Katharina , Serve Hubert , Bechstein Wolf Otto , Rieger Michael A.
Published: June 2021

Despite a high clinical need for the treatment of colorectal carcinoma (CRC) as the second leading cause of cancer-related deaths, targeted therapies are still limited. The multifunctional enzyme Transglutaminase 2 (TGM2), which harbors transamidation and GTPase activity, has been implicated in the development and progression of different types of human cancers. However, the mechanism and role of TGM2 in colorectal cancer are poorly understood. Here, we present TGM2 as a promising drug target.

In primary patient material of CRC patients, we detected an increased expression and enzymatic activity of TGM2 in colon cancer tissue in comparison to matched normal colon mucosa cells. The genetic ablation of TGM2 in CRC cell lines using shRNAs or CRISPR/Cas9 inhibited cell expansion and tumorsphere formation. In vivo, tumor initiation and growth were reduced upon genetic knockdown of TGM2 in xenotransplantations. TGM2 ablation led to the induction of Caspase-3-driven apoptosis in CRC cells. Functional rescue experiments with TGM2 variants revealed that the transamidation activity is critical for the pro-survival function of TGM2. Transcriptomic and protein–protein interaction analyses applying various methods including super-resolution and time-lapse microscopy showed that TGM2 directly binds to the tumor suppressor p53, leading to its inactivation and escape of apoptosis induction.

We demonstrate here that TGM2 is an essential survival factor in CRC, highlighting the therapeutic potential of TGM2 inhibitors in CRC patients with high TGM2 expression. The inactivation of p53 by TGM2 binding indicates a general anti-apoptotic function, which may be relevant in cancers beyond CRC.
Detection of acute ventilatory problems via magnetic induction in a newborn animal model
Authors: Behr Sabrina C. , Platen Christopher , Vetter Pascal , Heussen Nicole , Leonhardt Steffen , Orlikowsky Thorsten , Heimann Konrad
Published: June 2021

Background

Magnetic induction measurement (MIM) is a noninvasive method for the contactless registration of respiration in newborn piglets by using measurement coils positioned at the bottom of an incubator. Acute pulmonary problems may be determinants of poor neurological and psychomotor outcomes in preterm infants. The current study tested the detection of pulmonary ventilation disorders via MIM in 11 newborn piglets.

Methods

Six measurement coils determined changes in magnetic induction, depending on the ventilation of the lung, in comparison with flow resistance. Contactless registration of induced acute pulmonary ventilation disorders (apnea, atelectasis, pneumothorax, and aspiration) was detected by MIM.

Results

All pathologies except aspiration were detected by MIM. Significant changes occurred after induction of apnea (three coils), malposition of the tube (one coil), and pneumothorax (three coils) (p ≤ 0.05). No significant changes occurred after induction of aspiration (p = 0.12).

Conclusions

MIM seems to have some potential to detect acute ventilation disorders in newborn piglets. The location of the measurement coil related to the animal’s position plays a critical role in this process. In addition to an early detection of acute pulmonary problems, potential information pointing to a therapeutic intervention, for example, inhalations or medical respiratory analepsis, may be conceivable with MIM in the future.

Impact

MIM seems to be a method in which noncontact ventilation disorders of premature and mature infants can be detected.

This study is an extension of the experimental setup to obtain preliminary evidence for detection of respiratory activity in neonatal piglets. For the first time, MIM is used to register acute ventilation problems of neonates.

The possibility of an early detection of acute ventilation problems via MIM may provide an opportunity to receive patient-side information for therapeutical interventions like inhalations or medical respiratory analepsis.
G-MDSCs promote aging-related cardiac fibrosis by activating myofibroblasts and preventing senescence
Authors: Sun Shu-Ning , Ni Shi-Hao , Li Yue , Liu Xin , Deng Jian-Ping , Chen Zi-Xin , Li Huan , Feng Wen-Jun , Huang Yu-Sheng , Li Da-Nian , Xian Shao-Xiang , Yang Zhong-Qi , Wang Ling-Jun , Lu Lu
Published: June 2021

Aging is one of the most prominent risk factors for heart failure. Myeloid-derived suppressor cells (MDSCs) accumulate in aged tissue and have been confirmed to be associated with various aging-related diseases. However, the role of MDSCs in the aging heart remains unknown. Through RNA-seq and biochemical approaches, we found that granulocytic MDSCs (G-MDSCs) accumulated significantly in the aging heart compared with monocytic MDSCs (M-MDSCs). Therefore, we explored the effects of G-MDSCs on the aging heart. We found that the adoptive transfer of G-MDSCs of aging mice to young hearts resulted in cardiac diastolic dysfunction by inducing cardiac fibrosis, similar to that in aging hearts. S100A8/A9 derived from G-MDSCs induced inflammatory phenotypes and increased the osteopontin (OPN) level in fibroblasts. The upregulation of fibroblast growth factor 2 (FGF2) expression in fibroblasts mediated by G-MDSCs promoted antisenescence and antiapoptotic phenotypes of fibroblasts. SOX9 is the downstream gene of FGF2 and is required for FGF2-mediated and G-MDSC-mediated profibrotic effects. Interestingly, both FGF2 levels and SOX9 levels were upregulated in fibroblasts but not in G-MDSCs and were independent of S100A8/9. Therefore, a novel FGF2-SOX9 signaling axis that regulates fibroblast self-renewal and antiapoptotic phenotypes was identified. Our study revealed the mechanism by which G-MDSCs promote cardiac fibrosis via the secretion of S100A8/A9 and the regulation of FGF2-SOX9 signaling in fibroblasts during aging.
Genome-wide copy number variation analysis of hepatitis B infection in a Japanese population
Authors: Kikuchi Masataka , Kobayashi Kaori , Nishida Nao , Sawai Hiromi , Sugiyama Masaya , Mizokami Masashi , Tokunaga Katsushi , Nakaya Akihiro
Published: June 2021

Genome-wide association studies have been performed to identify common genetic variants associated with hepatitis B (HB). However, little is known about copy number variations (CNVs) in HB. In this study, we performed a genome-wide CNV analysis between 1830 healthy controls and 1031 patients with HB infection after quality control. Using signal calling by the Axiom Analysis Suite and CNV detection by PennCNV software, we obtained a total of 4494 CNVs across all individuals. The genes with CNVs that were found only in the HB patients were associated with the immune system, such as antigen processing. A gene-level CNV association test revealed statistically significant CNVs in the contactin 6 (CNTN6) gene. Moreover, we also performed gene-level CNV association tests in disease subgroups, including hepatocellular carcinoma patients, liver cirrhosis patients, and HBV carriers, including asymptomatic carriers and patients with HBV-derived chronic hepatitis. Our findings from germline cells suggested that patient-specific CNVs may be inherent genetic risk factors for HB.
Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers
Authors: Amin Ladan , Harris David A.
Published: June 2021

Several cell-surface receptors for neurotoxic forms of amyloid-β (Aβ) have been described, but their molecular interactions with Aβ assemblies and their relative contributions to mediating Alzheimer’s disease pathology have remained uncertain. Here, we used super-resolution microscopy to directly visualize Aβ-receptor interactions at the nanometer scale. We report that one documented Aβ receptor, PrPC, specifically inhibits the polymerization of Aβ fibrils by binding to the rapidly growing end of each fibril, thereby blocking polarized elongation at that end. PrPC binds neurotoxic oligomers and protofibrils in a similar fashion, suggesting that it may recognize a common, end-specific, structural motif on all of these assemblies. Finally, two other Aβ receptors, FcγRIIb and LilrB2, affect Aβ fibril growth in a manner similar to PrPC. Our results suggest that receptors may trap Aβ oligomers and protofibrils on the neuronal surface by binding to a common molecular determinant on these assemblies, thereby initiating a neurotoxic signal.
Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema
Authors: Szőke Dániel , Kovács Gábor , Kemecsei Éva , Bálint László , Szoták-Ajtay Kitti , Aradi Petra , Styevkóné Dinnyés Andrea , Mui Barbara L. , Tam Ying K. , Madden Thomas D. , Karikó Katalin , Kataru Raghu P. , Hope Michael J. , Weissman Drew , Mehrara Babak J. , Pardi Norbert , Jakus Zoltán
Published: June 2021

Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. We demonstrated that administration of a single low-dose of VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema by restoring lymphatic function without inducing any obvious adverse events. Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe a model for identifying the organ-specific physiological and pathophysiological roles of the lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic tool to reduce lymphedema.
Molecular evidence of SARS-CoV-2 in New York before the first pandemic wave
Authors: Hernandez Matthew M. , Gonzalez-Reiche Ana S. , Alshammary Hala , Fabre Shelcie , Khan Zenab , van De Guchte Adriana , Obla Ajay , Ellis Ethan , Sullivan Mitchell J. , Tan Jessica , Alburquerque Bremy , Soto Juan , Wang Ching-Yi , Sridhar Shwetha Hara , Wang Ying-Chih , Smith Melissa , Sebra Robert , Paniz-Mondolfi Alberto E. , Gitman Melissa R. , Nowak Michael D. , Cordon-Cardo Carlos , Luksza Marta , Krammer Florian , van Bakel Harm , Simon Viviana , Sordillo Emilia Mia
Published: June 2021

Numerous reports document the spread of SARS-CoV-2, but there is limited information on its introduction before the identification of a local case. This may lead to incorrect assumptions when modeling viral origins and transmission. Here, we utilize a sample pooling strategy to screen for previously undetected SARS-CoV-2 in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across the Mount Sinai Health System in New York. The patients had been previously evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We identify SARS-CoV-2 RNA from specimens collected as early as 25 January 2020, and complete SARS-CoV-2 genome sequences from multiple pools of samples collected between late February and early March, documenting an increase prior to the later surge. Our results provide evidence of sporadic SARS-CoV-2 infections a full month before both the first officially documented case and emergence of New York as a COVID-19 epicenter in March 2020.
Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix
Authors: Zhou Jujun , Horton John R. , Blumenthal Robert M. , Zhang Xing , Cheng Xiaodong
Published: June 2021

Clostridioides difficile infections are an urgent medical problem. The newly discovered C.difficileadenine methyltransferase A (CamA) is specified by all C. difficile genomes sequenced to date (>300), but is rare among other bacteria. CamA is an orphan methyltransferase, unassociated with a restriction endonuclease. CamA-mediated methylation at CAAAAA is required for normal sporulation, biofilm formation, and intestinal colonization by C. difficile. We characterized CamA kinetic parameters, and determined its structure bound to DNA containing the recognition sequence. CamA contains an N-terminal domain for catalyzing methyl transfer, and a C-terminal DNA recognition domain. Major and minor groove DNA contacts in the recognition site involve base-specific hydrogen bonds, van der Waals contacts and the Watson-Crick pairing of a rearranged A:T base pair. These provide sufficient sequence discrimination to ensure high specificity. Finally, the surprisingly weak binding of the methyl donor S-adenosyl-l-methionine (SAM) might provide avenues for inhibiting CamA activity using SAM analogs.
MOGONET integrates multi-omics data using graph convolutional networks allowing patient classification and biomarker identification
Authors: Wang Tongxin , Shao Wei , Huang Zhi , Tang Haixu , Zhang Jie , Ding Zhengming , Huang Kun
Published: June 2021

To fully utilize the advances in omics technologies and achieve a more comprehensive understanding of human diseases, novel computational methods are required for integrative analysis of multiple types of omics data. Here, we present a novel multi-omics integrative method named Multi-Omics Graph cOnvolutional NETworks (MOGONET) for biomedical classification. MOGONET jointly explores omics-specific learning and cross-omics correlation learning for effective multi-omics data classification. We demonstrate that MOGONET outperforms other state-of-the-art supervised multi-omics integrative analysis approaches from different biomedical classification applications using mRNA expression data, DNA methylation data, and microRNA expression data. Furthermore, MOGONET can identify important biomarkers from different omics data types related to the investigated biomedical problems.
Two decades of neuroscience publication trends in Africa
Authors: Maina M. B. , Ahmad U. , Ibrahim H. A. , Hamidu S. K. , Nasr F. E. , Salihu A. T. , Abushouk A. I. , Abdurrazak M. , Awadelkareem M. A. , Amin A. , Imam A. , Akinrinade I. D. , Yakubu A. H. , Azeez I. A. , Mohammed Y. G. , Adamu A. A. , Ibrahim H. B. , Bukar A. M. , Yaro A. U. , Goni B. W. , Prieto-Godino L. L. , Baden T.
Published: June 2021

Neuroscience research in Africa remains sparse. Devising new policies to boost Africa’s neuroscience landscape is imperative, but these must be based on accurate data on research outputs which is largely lacking. Such data must reflect the heterogeneity of research environments across the continent’s 54 countries. Here, we analyse neuroscience publications affiliated with African institutions between 1996 and 2017. Of 12,326 PubMed indexed publications, 5,219 show clear evidence that the work was performed in Africa and led by African-based researchers - on average ~5 per country and year. From here, we extract information on journals and citations, funding, international coauthorships and techniques used. For reference, we also extract the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our dataset provides insights into the current state of African neuroscience research in a global context.
Deep learning connects DNA traces to transcription to reveal predictive features beyond enhancer–promoter contact
Authors: Rajpurkar Aparna R. , Mateo Leslie J. , Murphy Sedona E. , Boettiger Alistair N.
Published: June 2021

Chromatin architecture plays an important role in gene regulation. Recent advances in super-resolution microscopy have made it possible to measure chromatin 3D structure and transcription in thousands of single cells. However, leveraging these complex data sets with a computationally unbiased method has been challenging. Here, we present a deep learning-based approach to better understand to what degree chromatin structure relates to transcriptional state of individual cells. Furthermore, we explore methods to “unpack the black box” to determine in an unbiased manner which structural features of chromatin regulation are most important for gene expression state. We apply this approach to an Optical Reconstruction of Chromatin Architecture dataset of the Bithorax gene cluster inDrosophilaand show it outperforms previous contact-focused methods in predicting expression state from 3D structure. We find the structural information is distributed across the domain, overlapping and extending beyond domains identified by prior genetic analyses. Individual enhancer-promoter interactions are a minor contributor to predictions of activity.
Saturated free fatty acids and association with memory formation
Authors: Wallis Tristan P. , Venkatesh Bharat G. , Narayana Vinod K. , Kvaskoff David , Ho Alan , Sullivan Robert K. , Windels François , Sah Pankaj , Meunier Frédéric A.
Published: June 2021

Polyunsaturated free fatty acids (FFAs) such as arachidonic acid, released by phospholipase activity on membrane phospholipids, have long been considered beneficial for learning and memory and are known modulators of neurotransmission and synaptic plasticity. However, the precise nature of other FFA and phospholipid changes in specific areas of the brain during learning is unknown. Here, using a targeted lipidomics approach to characterise FFAs and phospholipids across the rat brain, we demonstrated that the highest concentrations of these analytes were found in areas of the brain classically involved in fear learning and memory, such as the amygdala. Auditory fear conditioning led to an increase in saturated (particularly myristic and palmitic acids) and to a lesser extent unsaturated FFAs (predominantly arachidonic acid) in the amygdala and prefrontal cortex. Both fear conditioning and changes in FFA required activation of NMDA receptors. These results suggest a role for saturated FFAs in memory acquisition.
Mechanistic data-driven prediction of as-built mechanical properties in metal additive manufacturing
Authors: Xie Xiaoyu , Bennett Jennifer , Saha Sourav , Lu Ye , Cao Jian , Liu Wing Kam , Gan Zhengtao
Published: June 2021

Metal additive manufacturing provides remarkable flexibility in geometry and component design, but localized heating/cooling heterogeneity leads to spatial variations of as-built mechanical properties, significantly complicating the materials design process. To this end, we develop a mechanistic data-driven framework integrating wavelet transforms and convolutional neural networks to predict location-dependent mechanical properties over fabricated parts based on process-induced temperature sequences, i.e., thermal histories. The framework enables multiresolution analysis and importance analysis to reveal dominant mechanistic features underlying the additive manufacturing process, such as critical temperature ranges and fundamental thermal frequencies. We systematically compare the developed approach with other machine learning methods. The results demonstrate that the developed approach achieves reasonably good predictive capability using a small amount of noisy experimental data. It provides a concrete foundation for a revolutionary methodology that predicts spatial and temporal evolution of mechanical properties leveraging domain-specific knowledge and cutting-edge machine and deep learning technologies.
Trends in the hyperfine interactions of magnetic adatoms on thin insulating layers
Authors: Shehada Sufyan , dos Santos Dias Manuel , Guimarães Filipe Souza Mendes , Abusaa Muayad , Lounis Samir
Published: June 2021

Nuclear spins are among the potential candidates prospected for quantum information technology. A recent breakthrough enabled to atomically resolve their interaction with the electron spin, the so-called hyperfine interaction, within individual atoms utilizing scanning tunneling microscopy (STM). Intriguingly, this was only realized for a few species put on a two-layers thick MgO. Here, we systematically quantify from first-principles the hyperfine interactions of the whole series of 3d transition adatoms deposited on various thicknesses of MgO, NaF, NaCl, h–BN, and Cu2N films. We identify the adatom-substrate complexes with the largest hyperfine interactions and unveil the main trends and exceptions. We reveal the core mechanisms at play, such as the interplay of the local bonding geometry and the chemical nature of the thin films, which trigger transitions between high- and low-spin states accompanied with subtle internal rearrangements of the magnetic electrons. By providing a general map of hyperfine interactions, our work has immediate implications in future STM investigations aiming at detecting and realizing quantum concepts hinging on nuclear spins.
Full daylight quantum-key-distribution at 1550 nm enabled by integrated silicon photonics
Authors: Avesani M. , Calderaro L. , Schiavon M. , Stanco A. , Agnesi C. , Santamato A. , Zahidy M. , Scriminich A. , Foletto G. , Contestabile G. , Chiesa M. , Rotta D. , Artiglia M. , Montanaro A. , Romagnoli M. , Sorianello V. , Vedovato F. , Vallone G. , Villoresi P.
Published: June 2021

The future envisaged global-scale quantum-communication network will comprise various nodes interconnected via optical fibers or free-space channels, depending on the link distance. The free-space segment of such a network should guarantee certain key requirements, such as daytime operation and the compatibility with the complementary telecom-based fiber infrastructure. In addition, space-to-ground links will require the capability of designing light and compact quantum devices to be placed in orbit. For these reasons, investigating available solutions matching all the above requirements is still necessary. Here we present a full prototype for daylight quantum key distribution at 1550 nm exploiting an integrated silicon-photonics chip as state encoder. We tested our prototype in the urban area of Padua (Italy) over a 145 m-long free-space link, obtaining a quantum bit error rate around 0.5% and an averaged secret key rate of 30 kbps during a whole sunny day (from 11:00 to 20:00). The developed chip represents a cost-effective solution for portable free-space transmitters and a promising resource to design quantum optical payloads for future satellite missions.
Elimination of fosfomycin during dialysis with the Genius system in septic patients
Authors: Dimski T. , Brandenburger T. , Janczyk M. , Slowinski T. , MacKenzie C. , Kindgen-Milles D.
Published: June 2021

To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4–6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.
Cooperation and competition between pair and multi-player social games in spatial populations
Authors: Szolnoki Attila , Chen Xiaojie
Published: June 2021

The conflict between individual and collective interests is in the heart of every social dilemmas established by evolutionary game theory. We cannot avoid these conflicts but sometimes we may choose which interaction framework to use as a battlefield. For instance some people like to be part of a larger group while other persons prefer to interact in a more personalized, individual way. Both attitudes can be formulated via appropriately chosen traditional games. In particular, the prisoner’s dilemma game is based on pair interaction while the public goods game represents multi-point interactions of group members. To reveal the possible advantage of a certain attitude we extend these models by allowing players not simply to change their strategies but also let them to vary their attitudes for a higher individual income. We show that both attitudes could be the winner at a specific parameter value. Interestingly, however, the subtle interplay between different states may result in a counterintuitive evolutionary outcome where the increase of the multiplication factor of public goods game drives the population to a fully defector state. We point out that the accompanying pattern formation can only be understood via the multipoint or multi-player interactions of different microscopic states where the vicinity of a particular state may influence the relation of two other competitors.