bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations
Authors: Degenhardt Frauke , Mayr Gabriele , Wendorff Mareike , Boucher Gabrielle , Ellinghaus Eva , Ellinghaus David , ElAbd Hesham , Rosati Elisa , Hübenthal Matthias , Juzenas Simonas , Abedian Shifteh , Vahedi Homayon , Thelma B K , Yang Suk-Kyun , Ye Byong Duk , Cheon Jae Hee , Datta Lisa Wu , Daryani Naser Ebrahim , Ellul Pierre , Esaki Motohiro , Fuyuno Yuta , McGovern Dermot P B , Haritunians Talin , Hong Myhunghee , Juyal Garima , Jung Eun Suk , Kubo Michiaki , Kugathasan Subra , Lenz Tobias L , Leslie Stephen , Malekzadeh Reza , Midha Vandana , Motyer Allan , Ng Siew C , Okou David T , Raychaudhuri Soumya , Schembri John , Schreiber Stefan , Song Kyuyoung , Sood Ajit , Takahashi Atsushi , Torres Esther A , Umeno Junji , Alizadeh Behrooz Z , Weersma Rinse K , Wong Sunny H , Yamazaki Keiko , Karlsen Tom H , Rioux John D , Brant Steven R ,   for the MAAIS Recruitment Center, Franke Andre ,   for the International IBD Genetics Consortium
Published: January 2021

Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
Care the epicardial pacemaker wires
Authors: Gonçalves Luísa , Máximo José , Almeida Jorge , Pinho Paulo 
Published: January 2021

Abstract
A patient with previous CABG was hospitalized for fever and Staphylococcus aureus bacteraemia without cardiac involvement. After appropriate antibiotic cycle, the patient recovered and was discharged. Six months later, symptoms and bacteraemia relapsed. A small intriguing ‘cystic’ mass was visualized in the right atrium by echocardiography. Once again, was discharged after successful antibiotic treatment. Four months later, symptoms and Staphylococcus bacteraemia reappeared with increasing mass size and surgery was decided. Intraoperatively, it was perceived that the mass was related to an epicardial pacemaker wire. Retained epicardial wires should be remembered in endocarditis evaluation.
Behavioral Deficits Induced by Somatostatin-Positive GABA Neuron Silencing Are Rescued by Alpha 5 GABA-A Receptor Potentiation
Authors: Fee Corey , Prevot Thomas D , Misquitta Keith , Knutson Daniel E , Li Guanguan , Mondal Prithu , Cook James M , Banasr Mounira , Sibille Etienne 
Published: January 2021

Abstract

Introduction
Deficits in somatostatin-positive gamma-aminobutyric acid interneurons (SST+ GABA cells) are commonly reported in human studies of mood and anxiety disorder patients. A causal link between SST+ cell dysfunction and symptom-related behaviors has been proposed based on rodent studies showing that chronic stress, a major risk factor for mood and anxiety disorders, induces a low SST+ GABA cellular phenotype across corticolimbic brain regions; that lowering Sst, SST+ cell, or GABA functions induces depressive-/anxiety-like behaviors (a rodent behavioral construct collectively defined as “behavioral emotionality”); and that disinhibiting SST+ cells has antidepressant-like effects. Recent studies found that compounds preferentially potentiating receptors mediating SST+ cell functions, α5-GABAA receptor positive allosteric modulators (α5-PAMs), achieved antidepressant-like effects. Together, the evidence suggests that SST+ cells regulate mood and cognitive functions that are disrupted in mood disorders and that rescuing SST+ cell function via α5-PAM may represent a targeted therapeutic strategy.

Methods
We developed a mouse model allowing chemogenetic manipulation of brain-wide SST+ cells and employed behavioral characterization 30 minutes after repeated acute silencing to identify contributions to symptom-related behaviors. We then assessed whether an α5-PAM, GL-II-73, could rescue behavioral deficits.

Results
Brain-wide SST+ cell silencing induced features of stress-related illnesses, including elevated neuronal activity and plasma corticosterone levels, increased anxiety- and anhedonia-like behaviors, and impaired short-term memory. GL-II-73 led to antidepressant- and anxiolytic-like improvements among behavioral deficits induced by brain-wide SST+ cell silencing.

Conclusion
Our data validate SST+ cells as regulators of mood and cognitive functions and demonstrate that bypassing low SST+ cell function via α5-PAM represents a targeted therapeutic strategy.
Complementary and competitive framing of driverless cars: framing effects, attitude volatility, or attitude resistance?
Authors: Ho Shirley S 
Published: January 2021

AbstractThis study answers two research questions regarding framing theory. First, what happens when frames are challenged? Second, how resistant are the opinions that initial frames induce? 1,006 participants completed an online experiment where they were randomly assigned to first view a blog post with either complementary or competitive framing on driverless cars. Participants also viewed a blog post that challenged the stance of the first blog post. Results revealed that complementary frames polarized opinions, while competitive frames neutralized framing effects. Competitive frames induced more resistant opinions than complementary frames did. Attitude and support were susceptible to new, antagonistic information. This study concludes that framing effects are ephemeral and easily challenged by different information.
Development and validation of a machine learning model predicting illness trajectory and hospital utilization of COVID-19 patients: A nationwide study
Authors: Roimi Michael , Gutman Rom , Somer Jonathan , Ben Arie Asaf , Calman Ido , Bar-Lavie Yaron , Gelbshtein Udi , Liverant-Taub Sigal , Ziv Arnona , Eytan Danny , Gorfine Malka , Shalit Uri 
Published: January 2021

Abstract

Objective
The spread of coronavirus disease 2019 (COVID-19) has led to severe strain on hospital capacity in many countries. We aim to develop a model helping planners assess expected COVID-19 hospital resource utilization based on individual patient characteristics.

Materials and Methods
We develop a model of patient clinical course based on an advanced multistate survival model. The model predicts the patient's disease course in terms of clinical states—critical, severe, or moderate. The model also predicts hospital utilization on the level of entire hospitals or healthcare systems. We cross-validated the model using a nationwide registry following the day-by-day clinical status of all hospitalized COVID-19 patients in Israel from March 1 to May 2, 2020 (n = 2703).

Results
Per-day mean absolute errors for predicted total and critical care hospital bed utilization were 4.72 ± 1.07 and 1.68 ± 0.40, respectively, over cohorts of 330 hospitalized patients; areas under the curve for prediction of critical illness and in-hospital mortality were 0.88 ± 0.04 and 0.96 ± 0.04, respectively. We further present the impact of patient influx scenarios on day-by-day healthcare system utilization. We provide an accompanying R software package.

Discussion
The proposed model accurately predicts total and critical care hospital utilization. The model enables evaluating impacts of patient influx scenarios on utilization, accounting for the state of currently hospitalized patients and characteristics of incoming patients. We show that accurate hospital load predictions were possible using only a patient’s age, sex, and day-by-day clinical state (critical, severe, or moderate).

Conclusions
The multistate model we develop is a powerful tool for predicting individual-level patient outcomes and hospital-level utilization.
Analytical Study of the Antifungal Posaconazole in Raw Material: Quantitative Bioassay, Decomposition Chemical Kinetics, and Degradation Impurities by LC-QTOF-MS
Authors: Garcia Cássia V , Bitencourt Andressa S , Oliveira Sendy S , Gobetti Caren , Mendez Andreas S L 
Published: January 2021

Abstract

Background
Posaconazole is a triazole antifungal drug that was approved by the U.S. Food and Drug Administration in 2006. No bioassay of it is available in the literature nor official codes for potency determination in bulk.

Objective
To conduct an analytical study focused on posaconazole in bulk.

Methods
An alternative microbiological assay was validated for drug quantitation, applying agar diffusion technics (3 × 3 design), using Saccharomyces cerevisiae ATCC MYA 1942 as a test microorganism (2% inoculum). An isocratic HPLC–DAD method, with C8 Shim-pack column (250 × 4.6 mm, 5 μm) and methanol–water (75:25 v/v) mobile phase was used for stress stability by photolysis and oxidation, indicating the formation of degradation products, which were investigated by ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry.

Results
The established conditions for the bioassay were satisfactory. It was linear in the range evaluated (2.5–10.0 µg/mL), as well as precise, accurate, and robust. Stress tests showed drug susceptibility to the factors evaluated (60% of degradation after 120 min). Kinetics curves for photolytic decomposition followed first-order kinetics. From a photolytic and oxidative degraded matrix, three major degradation products were identified as being derivatives with modifications in the piperazine central ring and in the triazole and triazolone side chains, whose mass spectra results were m/z 683 (DP1), m/z 411 (DP2), and m/z 465 (DP3).

Conclusions
The microbiological method was adequately validated and demonstrated to be equivalent to physico-chemical ones. The impurities found are described for the first time in studies with posaconazole raw material.

Highlights
A microbiological bioassay was developed for posaconazole, first-order kinetics was determined for photolytic degradation, and structures for new degradation products were suggested.
Expression and affinity purification of recombinant mammalian mitochondrial ribosomal small subunit (MRPS) proteins and protein–protein interaction analysis indicate putative role in tumourigenic cellular processes
Authors: Revathi Paramasivam Oviya , Gopisetty Gopal , Subramani Jayavelu , Thangarajan Rajkumar 
Published: January 2021

Abstract
Mitochondrial ribosomal small subunit (MRPS) group of proteins is structural constituents of the small subunit of mitoribosomes involved in translation. Recent studies indicate role in tumourigenic process, however, unlike cytosolic ribosomal proteins, knowledge on the role of MRPS proteins in alternate cellular processes is very limited. Mapping protein–protein interactions (PPIs) onto known cellular processes can be a valuable tool to identify novel protein functions. In this study, to identify PPIs of MRPS proteins, we have constructed 31 glutathione-S-transferase (GST)/MRPS fusion clones. GST/MRPS fusion proteins were confirmed by MALDI-TOF analysis. GST pull-downs were performed using eight GST/MRPS proteins (MRPS9, MRPS10, MRPS11, MRPS18B, MRPS31, MRPS33, MRPS38 and MRPS39), GST alone as pull-down control and HEK293 cell lysate as the source for anchor proteins followed by nLC/MS/MS analysis and probable PPIs of eight MRPS proteins were identified. Three PPIs from GST pull-downs and interaction between six MRPS proteins and p53 previously reported in PPI database were validated. The PPI network analysis revealed putative role in cellular processes with implications for tumourigenesis. Gene expression screening of a cancer cell line panel indicated overexpression of MRPS10 and MRPS31 in breast cancer. Co-expression module identification tool analysis of breast cancer gene expression and MRPS10 and MRPS31 PPIs revealed putative role for PPI with acyl-CoA dehydrogenase in fatty acid oxidation process regulated by brain-derived neurotrophic factor signalling pathway.
Buzz-Pollinated Crops: A Global Review and Meta-analysis of the Effects of Supplemental Bee Pollination in Tomato
Authors: Cooley Hazel , Vallejo-Marín Mario 
Published: January 2021

AbstractBuzz-pollinated plants require visitation from vibration producing bee species to elicit full pollen release. Several important food crops are buzz-pollinated including tomato, eggplant, kiwi, and blueberry. Although more than half of all bee species can buzz pollinate, the most commonly deployed supplemental pollinator, Apis mellifera L. (Hymenoptera: Apidae; honey bees), cannot produce vibrations to remove pollen. Here, we provide a list of buzz-pollinated food crops and discuss the extent to which they rely on pollination by vibration-producing bees. We then use the most commonly cultivated of these crops, the tomato, Solanum lycopersicum L. (Solanales: Solanaceae), as a case study to investigate the effect of different pollination treatments on aspects of fruit quality. Following a systematic review of the literature, we statistically analyzed 71 experiments from 24 studies across different geopolitical regions and conducted a meta-analysis on a subset of 21 of these experiments. Our results show that both supplemental pollination by buzz-pollinating bees and open pollination by assemblages of bees, which include buzz pollinators, significantly increase tomato fruit weight compared to a no-pollination control. In contrast, auxin treatment, artificial mechanical vibrations, or supplemental pollination by non-buzz-pollinating bees (including Apis spp.), do not significantly increase fruit weight. Finally, we compare strategies for providing bee pollination in tomato cultivation around the globe and highlight how using buzz-pollinating bees might improve tomato yield, particularly in some geographic regions. We conclude that employing native, wild buzz pollinators can deliver important economic benefits with reduced environmental risks and increased advantages for both developed and emerging economies.
Comparative Pathogenesis of Generalist AcMNPV and Specific RanuNPV in Larvae of Rachiplusia nu (Lepidoptera: Noctuidae) Following Single and Mixed Inoculations
Authors: Decker-Franco Cecilia , Taibo Catalina B , Di Rienzo Julio A , Alfonso Victoria , Arneodo Joel D 
Published: January 2021

Abstract
The South American soybean pest, Rachiplusia nu (Guenée), is naturally infected by Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Rachiplusia nu nucleopolyhedrovirus (RanuNPV). We compared their pathogenicity to fourth-instar R. nu larvae, by evaluating time to death and virus spread throughout the tissues in single and mixed infections. Bioassays showed that generalist AcMNPV had a faster speed of kill than specific RanuNPV, while the mixed-virus treatment did not statistically differ from AcMNPV alone. Histopathology evidenced similar tissue tropism for both viruses, but co-inoculation resulted in mostly AcMNPV-infected cells. In sequential inoculations, however, the first virus administered predominated over the second one. Implications on baculovirus interactions and biocontrol potential are discussed.
Does human germline genome editing violate human dignity? An African perspective
Authors: Shozi Bonginkosi 
Published: January 2021

ABSTRACT
It has been variously claimed that alterations to the human genome for reproductive purposes ought to be prohibited on the basis that doing so is contrary to human dignity. This claim leads to the conclusion that germline genome editing (GGE) ought to be categorically banned in all states committed to upholding human dignity as a right recognized in international human rights documents, and which has been entrenched in the constitutions of many liberal democracies. But is it the case that the right to human dignity is necessarily opposed to GGE? This paper explores this question through critical examination of the concept of human dignity in international human rights, and how it has been interpreted by individual states. Recognizing that the interpretation of human dignity is shaped by cultural context, the paper explores an African perspective on this issue, using South African constitutional jurisprudence on human dignity as an example. It concludes that when viewed through the lens of the African ethic of Ubuntu, there is no justification for a categorical prohibition on GGE, on the grounds that it is contrary to human dignity. This illustrates the need for a global discourse on the regulation on genome editing to be sensitive to varying perspectives—specifically on value-laden questions such as the interpretation of human rights.
Protected areas and unpaved roads mediate habitat use of the giant anteater in anthropogenic landscapes
Authors: Versiani Natalia F , Bailey Larissa L , Pasqualotto Nielson , Rodrigues Thiago F , Paolino Roberta M , Alberici Vinicius , Chiarello Adriano G 
Published: January 2021

AbstractThe drastic reduction of the Brazilian Cerrado has transformed this savanna hotspot into vast swaths of commodity-based agriculture fields, mainly soybean, sugarcane, and beef-production pasturelands. The resulting habitat loss and fragmentation are the principal factors underlying population decline of native species inhabiting the Cerrado, particularly those with a high demand for space, low population density, and specialized diet, such as the endangered giant anteater (Myrmecophaga tridactyla). Although the species has been studied in protected areas, we know much less about its ability to endure in disturbed landscapes. Here, we analyzed camera-trapping data to estimate a proxy of habitat use (ψ^; occupancy) and detection probabilities of the giant anteater, identifying environmental covariates influencing these parameters in landscapes with intensive agriculture and commercial forestry. We found this species using about half of the study area (model average ψ^ = 0.51, CI = 0.40–0.62), with two predictors strongly influencing habitat use: protected areas and unpaved roads. In turn, detection probability correlates positively with area of open Cerrado and negatively with area of settlements. The species is more likely to use unpaved roads inside protected areas (ψ^ = 0.90, CI = 0.47–0.75), compared to off road sites in the surrounding areas (ψ^ = 0.19, CI = 0.10–0.34). Our findings indicate that giant anteaters are dependent on nature reserves and native vegetation areas existing on private properties, whose protection is regulated by the Brazilian Native Vegetation Protection Law. Given the relative paucity of state-owned protected areas in the Brazilian Cerrado, increasing the adherence of rural owners to this law is, therefore, key for the conservation of the giant anteater. The intense use of unpaved roads might reflect travelling and/or foraging optimization, a behavioral response that, nevertheless, may compound this species’ susceptibility to suffer mortality from roadkill.
Colorectal Cancer Risk by Genetic Variants in Populations With and Without Colonoscopy History
Authors: Guo Feng , Chen Xuechen , Chang-Claude Jenny , Hoffmeister Michael , Brenner Hermann 
Published: January 2021

Abstract

Background
Polygenic risk scores (PRS), which are derived from results of large genome-wide association studies, are increasingly propagated for colorectal cancer (CRC) risk stratification. The majority of studies included in the large genome-wide association studies consortia were conducted in the United States and Germany, where colonoscopy with detection and removal of polyps has been widely practiced over the last decades. We aimed to assess if and to what extent the history of colonoscopy with polypectomy may alter metrics of the predictive ability of PRS for CRC risk.

Methods
A PRS based on 140 single nucleotide polymorphisms was compared between 4939 CRC patients and 3797 control persons of the Darmkrebs: Chancen der Verhütung durch Screening (DACHS) study, a population-based case-control study conducted in Germany. Risk discrimination was quantified according to the history of colonoscopy and polypectomy by areas under the curves (AUCs) and their 95% confidence intervals (CIs). All statistical tests were 2-sided.

Results
AUCs and 95% CIs were higher among subjects without previous colonoscopy (AUC = 0.622, 95% CI = 0.606 to 0.639) than among those with previous colonoscopy and polypectomy (AUC = 0.568, 95% CI = 0.536 to 0.601; difference [Δ AUC] = 0.054, P = .004). Such differences were consistently seen in sex-specific groups (women: Δ AUC = 0.073, P = .02; men: Δ AUC = 0.046, P = .048) and age-specific groups (younger than 70 years: Δ AUC = 0.052, P = .07; 70 years or older: Δ AUC = 0.049, P = .045).

Conclusions
Predictive performance of PRS may be underestimated in populations with widespread use of colonoscopy. Future studies using PRS to develop CRC prediction models should carefully consider colonoscopy history to provide more accurate estimates.
Primary renal lymphoma: unique presentation in a rare disease
Authors: Youssef Mohamed , Davis Faustina , Rao Praveen 
Published: January 2021

Abstract
As the kidney is an extra-nodal organ and does not have lymphatic tissues, the existence of primary renal non-Hodgkin’s lymphoma has been continuously questioned. It is very rare. However, differentiation between renal cell carcinoma and renal lymphoma is necessary in patients presenting with solitary renal mass. We present a 70-year-old-man who presented with a renal mass and was diagnosed with diffuse large B-cell lymphoma. We feel that this case report may be of benefit to clinicians who may encounter a similar scenario.
Extracorporeal cardiopulmonary resuscitation for the treatment of amlodipine overdose in a pediatric patient
Authors: Giuliano Katherine , Chen Y Julia , Coletti Kristen , O’Brien Caitlin , Jelin Eric , Garcia Alejandro 
Published: January 2021

Abstract
We present the case of a 16-year-old female with systemic lupus erythematosus who presented with shock of unclear etiology, refractory to fluid resuscitation and triple vasopressors. She suffered pulseless electrical activity and underwent cannulation onto veno-arterial extracorporeal membrane oxygenation (ECMO). After cannulation, it was discovered she had intentionally overdosed on her home medication, amlodipine, a calcium channel blocker (CCB). She was supported on ECMO, treated with IV calcium and insulin, and was able to be weaned off ECMO after 4 days. She developed oligoanuric acute kidney injury, treated with continuous renal replacement therapy followed by intermittent hemodialysis. At discharge, she was neurologically intact and did not require dialysis. Herein, we review the treatment of CCB overdose, review the literature on the use of ECMO in refractory shock due to cardiovascular medication overdose, and highlight the utility of ECMO in pediatric refractory shock and/or cardiac arrest of unclear etiology.