bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the dyslipidemias: to fast or not to fast?
Authors: Farukhi Zareen , Mora Samia 
Published: January 2021

Purpose of review
Nonfasting lipid testing has been introduced into several guidelines over the past decade or so however, the uptake into clinical practice has not been universal. This review highlights some of the prevalent reasons for provider reluctance to use nonfasting testing and the evidence to support nonfasting testing for routine screening in most patients.

Recent findings
Several studies have found nonfasting lipids to be as, or more, strongly associated with cardiovascular disease (CVD) risk prediction. In particular, nonfasting tests improve system efficiency, are safe for patients with diabetes, the elderly, children, and in the vast majority of patients, do not need to be followed up with fasting studies due to severe hypertriglyceridemia.

Summary
Nonfasting lipids are a convenient first test for screening that offers equivalent, if not improved CVD risk prediction. Common misconceptions about nonfasting tests are not supported by the evidence.
Targeted pharmacotherapy of irritable bowel syndrome
Authors: Arokiadoss Abishek , Weber H. Christian 
Published: January 2021

Purpose of review
Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal (GI) disorder with negative impact on quality of life and it represents a substantial economic burden on healthcare cost. The medical management of IBS is symptom directed. This review provides an update related to clinical trial data for novel treatment modalities in IBS targeting the gut epithelium secretagogue receptors and channels.

Recent findings
The new Rome IV criteria define functional gastrointestinal disorders (FGID) as disorders of the gut–brain interaction. Pharmacological treatment modalities for IBS target gastrointestinal receptors and ion channels, peripheral opioid receptor, gut serotonin receptors, and the gut microbiome. New targeted pharmacotherapies have shown efficacy and safety in the treatment of patients with IBS.

Summary
Diagnostic criteria for FGID, including IBS, have been revised in Rome IV and are defined as gut-brain disorders. Newly approved pharmacotherapy options with proven efficacy and acceptable side-effect profiles are available for the symptom-based management of IBS.
Changes in Patient Reported Pain Measures With the Citrate-free Adalimumab Formulation in Pediatric Inflammatory Bowel Disease Patients
Authors: Patel Ashish S. , Luu Phuong 
Published: January 2021

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation in the gastrointestinal tract. The perception of pain in children is very complex and involves psychological, physiological, behavioral, and developmental factors. For children with chronic diseases, the medical procedures and treatments are often painful, unexpected, and heightened by situational stress and anxiety leading to an overall unpleasant experience. Pain and injection-site reaction are major predictors of nonadherence to antitumor necrosis factor treatment.
The most commonly reported adalimumab adverse event was injection-site reaction. This study compares reported pain in pediatric IBD patients between the 2 formulations using a visual analog scale (VAS). Our hypothesis is that the citrate-free formulation would have significantly less injection-site pain than the original formulation.
We evaluated injection-site pain in 6- to 17-year olds with IBD between the original formulation and citrate-free using the Faces Pain Scale-Revised for pain from 0 (no pain) to 10 (worse pain possible).
Ninety-five percent of patients reported that their pain score was greater than 3 with original formulation, while only 5% of them reported their pain score was greater than 3 with citrate free. The McNemar’s test showed significant difference in the pain score between the 2 types of injection (P < 0.0001).
Gut Microbial Changes and their Contribution to Post-Burn Pathology
Authors: Luck Marisa E. , Herrnreiter Caroline J. , Choudhry Mashkoor A. 
Published: January 2021

ABSTRACT
Burn injuries are a common form of traumatic injury that leads to significant morbidity and mortality worldwide. Burn injuries are characterized by inflammatory processes and alterations in numerous organ systems and functions. Recently, it has become apparent that the gastrointestinal bacterial microbiome is a key component of regulating the immune response and recovery from burn and can also contribute to significant detrimental sequelae after injury, such as sepsis and multiple organ failure. Microbial dysbiosis has been linked to multiple disease states; however, its role in exacerbating acute traumatic injuries, such as burn, is poorly understood. In this article, we review studies that document changes in the intestinal microbiome after burn injury, assess the implications in post-burn pathogenesis, and the potential for further discovery and research.
Clinicopathological Analysis of Uterine Allografts Including Proposed Scoring of Ischemia Reperfusion Injury and T-cell–mediated Rejection—Dallas UtErus Transplant Study: A Pilot Study
Authors: Agarwal Atin , Johannesson Liza , Findeis Sarah K. , Punar Metin , Askar Medhat , Ma Tsung-Wei , Pinto Karen , Demetris Anthony J. , Testa Giuliano 
Published: January 2021

Background.
Uterus transplantation (UTx) enables pregnancy in infertile women. This study describes the histopathological changes of ischemia reperfusion injury and mostly acute T-cell–mediated rejection (TCMR) in UTx and proposes modification toward a working formulation grading system with associated treatments.

Methods.
Protocol and indication biopsies from 11 living and 2 deceased donor UTx recipients were analyzed. Serving as a control were 49 age-matched nontransplanted uteri. All posttransplant histopathological specimens were evaluated in a blinded fashion by 3 pathologists. Response to treatment was assessed by follow-up biopsies. Serial serum donor-specific antibody (DSA) responses were also recorded.

Results.
Changes attributed to ischemia reperfusion resolved within 2 wk of UTx in most of the patients. For TCMR grading, perivascular inflammation, focal capillary disruption, and interstitial hemorrhage were added to interface inflammation, intercellular edema, stromal inflammation, and epithelial apoptotic bodies. Of the 173 protocol biopsies, 98 were classified as negative for TCMR; 34 as indeterminate-borderline; 35 as mild; 3 as moderate; and 3 as severe, 1 of which occurred in a DSA-positive recipient and also showed microvascular injury. Corticosteroids successfully treated all moderate-to-severe TCMR episodes. Mild TCMR was treated by increasing existing baseline immunosuppression. Indeterminate-borderline episodes were not treated. Neither ischemia-reperfusion injury nor TCMR with DSA adversely affected embryo transfer.

Conclusions.
Relying on a modified histopathological grading system, we developed a treatment strategy resulting in resolution of TCMR and successful pregnancies.
Retrospective SARS-CoV-2 Real-Time PCR Testing of Stored Bronchoalveolar Lavage Samples from February 2020
Authors: Challener Douglas , Shah Aditya , Binnicker Matthew , Badley Andrew , O’Horo John 
Published: January 2021

AbstractBronchoalveolar lavage samples (n=34) collected in February, 2020 prior to the wide availability of molecular testing for SARS-CoV-2 were retrospectively assayed for presence of viral RNA. None of these patients qualified for SARS-CoV-2 testing based on Centers for Disease Control criteria at the time. None of the samples tested positive for SARS-CoV-2, suggesting that the virus was not yet widespread in Minnesota at the time these samples were obtained.
Head-to-head comparison of direct-input RT-PCR and RT-LAMP against RT-qPCR on extracted RNA for rapid SARS-CoV-2 diagnostics
Authors: Kellner Max J. , Matl Martin , Ross James J. , Schnabl Jakob , Handler Dominik , Heinen Robert , Schaeffer Justine , Hufnagl Peter , Indra Alexander , Dekens Marcus P.S. , Fritsche-Polanz Robert , Födinger Manuela , Zuber Johannes ,   Vienna Covid-19 Detection Initiative (VCDI), Allerberger Franz , Pauli Andrea , Brennecke Julius 
Published: January 2021

SUMMARYViral pandemics, such as Covid-19, pose serious threats to human societies. To control the spread of highly contagious viruses such as SARS-CoV-2, effective test-trace-isolate strategies require population-wide, systematic testing. Currently, RT-qPCR on extracted RNA is the only broadly accepted test for SARS-CoV-2 diagnostics, which bears the risk of supply chain bottlenecks, often exaggerated by dependencies on proprietary reagents. Here, we directly compare the performance of gold standard diagnostic RT-qPCR on extracted RNA to direct input RT-PCR, RT-LAMP and bead-LAMP on 384 primary patient samples collected from individuals with suspected Covid-19 infection. With a simple five minute crude sample inactivation step and one hour of total reaction time, we achieve assay sensitivities of 98% (direct RT-PCR), 93% (bead-LAMP) and 82% (RT-LAMP) for clinically relevant samples (diagnostic RT-qPCR Ct <35) and a specificity of >98%. For direct RT-PCR, our data further demonstrate a perfect agreement between real-time and end-point measurements, which allow a simple binary classification similar to the powerful visual readout of colorimetric LAMP assays. Our study provides highly sensitive and specific, easy to implement, rapid and cost-effective alternatives to diagnostic RT-qPCR tests.
The Association of COVID-19 Incidence with Sport and Face Mask Use in United States High School Athletes
Authors: Watson Andrew M. , Haraldsdottir Kristin , Biese Kevin , Goodavish Leslie , Stevens Bethany , McGuine Timothy 
Published: January 2021

ABSTRACTPurposeTo evaluate the influence of sport characteristics and face mask use on COVID-19 incidence among high school athletes.MethodsSurveys were distributed to high school athletic directors throughout the United States regarding sport re-initiation, COVID-19 cases, and risk reduction procedures in fall 2020.Separate mixed effects Poisson regression models were developed to evaluate the associations between reported COVID-19 incidence and 1) sport characteristics (contact/non-contact, individual/team, indoor/outdoor) and 2) face mask use while playing (yes/no).Results991 schools had restarted fall sports, representing 152,484 athletes on 5,854 teams. 2,565 cases of COVID-19 were reported, representing a case rate of 1,682 cases per 100,000 athletes and an incidence rate of 24.6 cases per 100,000 player-days. COVID-19 incidence was lower among outdoor versus indoor sports (incidence rate ratio [IRR]=0.54, 95% CI=0.49-0.60, p<0.001) and non-contact versus contact sports (IRR=0.78 [0.70-0.87], p<0.001), but not team versus individual sports (IRR=0.96 [0.84-1.1], p=0.49). Face mask use was associated with a decreased incidence in girls’ volleyball (IRR=0.53 [0.37-0.73], p<0.001), boys’ basketball (IRR=0.53 [0.33-0.83], p=0.008) and girls’ basketball (IRR=0.36 [0.19-0.63], p<0.001), and approached statistical significance in football (IRR=0.79 [0.59-1.04], p=0.10) and cheer/dance (IRR=0.75 [0.53-1.03], p=0.081).ConclusionsIn this nationwide survey of US high school athletic directors representing 152,484 athletes, lower COVID-19 incidence was independently associated with participation in outdoor versus indoor and non-contact versus contact sports, but not team versus individual sports. Face mask use was associated with decreased COVID-19 incidence among indoor sports, and may be protective among outdoor sports with prolonged close contact between participants.
Clinical Associations of Functional Dyspepsia with Gastric Dysrhythmia on Electrogastrography: A Comprehensive Systematic Review and Meta-Analysis
Authors: Varghese C , Carson DA , Bhat S , Hayes TCL , Gharibans AA , Andrews CN , O’Grady G 
Published: January 2021

AbstractBackgroundFunctional dyspepsia (FD) is a common gastroduodenal disorder, yet its pathophysiology remains poorly understood. Bioelectrical gastric slow wave abnormalities are thought to contribute to its multifactorial pathophysiology. Electrogastrography (EGG) has been used to record gastric electrical activity, however the clinical associations require further evaluation.AimsThis study aimed to systematically assess the clinical associations of EGG in FD.MethodsMEDLINE, EMBASE, and CENTRAL databases were systematically searched for articles using EGG in adults with FD. Primary outcomes were percentage normal vs abnormal rhythm (bradygastria, normogastria, tachygastria). Secondary outcomes were dominant power, dominant frequency, percentage coupling and the meal responses.Results1751 FD patients and 555 controls from 47 studies were included. FD patients spent less time in normogastria while fasted (SMD −0.74; 95%CI −1.22 - −0.25) and postprandially (−0.86; 95%CI −1.35 - −0.37) compared to controls. FD patients also spent more fasted time in bradygastria (0.63; 95%CI 0.33 – 0.93) and tachygastria (0.45; 95%CI 0.12 – 0.78%). The power ratio (−0.17; 95%CI −0.83 - 0.48), and dominant frequency meal-response ratio (0.06; 95%CI −0.08 - 0.21) were not significantly different to controls. Correlations between EGG metrics and the presence and timing of FD symptoms were inconsistent. EGG methodologies were diverse and variably applied.ConclusionAbnormal gastric slow wave rhythms are a consistent abnormality present in FD, as defined by EGG, and therefore likely play a role in pathophysiology. The aberrant electrophysiology identified in FD warrants further investigation, including into underlying mechanisms, associated spatial patterns, and symptom correlations.
N-glycan chitobiose core biosynthesis by Agl24 strengthens the hypothesis of an archaeal origin of the eukaryal N-glycosylation
Authors: Meyer Benjamin H. , Wagstaff Ben A. , Adam Panagiotis S. , Albers Sonja-Verena , Dorfmueller Helge C. 
Published: January 2021

AbstractProtein N-glycosylation is the most common posttranslational modifications found in all three domains of life. The crenarchaeal N-glycosylation begins with the synthesis of a lipid-linked chitobiose core structure, identical to that in eukaryotes. Here, we report the identification of a thermostable archaeal beta-1,4-N-acetylglucosaminyltransferase, named archaeal glycosylation enzyme 24 (Agl24), responsible for the synthesis of the N-glycan chitobiose core. Biochemical characterization confirmed the function as an inverting β-D-GlcNAc-(1→4)-α-D-GlcNAc-diphosphodolichol glycosyltransferase. Substitution of a conserved histidine residue, found also in the eukaryotic and bacterial homologs, demonstrated its functional importance for Agl24. Furthermore, bioinformatics and structural modeling revealed strong similarities between Agl24 and both the eukaryotic Alg14/13 and a distant relation to the bacterial MurG, which catalyze the identical or a similar process, respectively. Our data, complemented by phylogenetic analysis of Alg13 and Alg14, revealed similar sequences in Asgardarchaeota, further supporting the hypothesis that the Alg13/14 homologs in eukaryotes have been acquired during eukaryogenesis.HighlightsFirst identification and characterization of a thermostable β-D-GlcNAc-(1→4)-α-D-GlcNAc-diphosphodolichol glycosyltransferase (GT family 28) in Archaea.A highly conserved histidine, within a GGH motif in Agl24, Alg14, and MurG, is essential for function of Agl24.Agl24-like homologs are broadly distributed among Archaea.The eukaryotic Alg13 and Alg14 are closely related to the Asgard homologs, suggesting their acquisition during eukaryogenesis.
Conserved and non-conserved triggers of 24-nt reproductive phasiRNAs in eudicots
Authors: Pokhrel Suresh , Huang Kun , Meyers Blake C. 
Published: January 2021

AbstractPlant small RNAs (sRNAs) play important roles in plant growth and development by modulating expression of genes and transposons. In many flowering plant species, male reproductive organs, the anthers, produce abundant phased small interfering RNAs (phasiRNAs). Two classes of reproductive phasiRNAs are generally known, mostly from monocots: pre-meiotic 21-nt phasiRNAs triggered by miR2118, and meiotic 24-nt phasiRNAs triggered by miR2275. Here, we describe conserved and non-conserved triggers of 24-nt phasiRNAs in several eudicots. We found that the abundant 24-nt phasiRNAs in the basal eudicot columbine are produced by the canonical trigger, miR2275, as well as by other non-conserved triggers, miR482/2118 and aco_cand81. These triggering miRNAs are localized in microspore mother cells (MMC) and tapetal cells of meiotic and post-meiotic stage anthers. Furthermore, we identified a new trigger (miR11308) of 24-nt phasiRNAs and an expanded number of 24-PHASloci in wild strawberry. We validated the presence of miR2275-derived 24-nt phasiRNAs pathway in rose. Finally, we evaluated all the eudicots that have been validated for the presence of 24-nt phasiRNAs as models to study biogenesis and function of 24-nt phasiRNAs and conclude that columbine would be an excellent model because of its extensive number of 24-PHASloci and its diversity of trigger miRNAs.
Adaptive laboratory evolution triggers pathogen-dependent broad-spectrum antimicrobial potency inStreptomyces
Authors: Harwani Dharmesh , Begani Jyotsna , Barupal Sweta , Lakhani Jyoti 
Published: January 2021

AbstractIn the present study, adaptive laboratory evolution was used to stimulate antibiotic production in a weak antibiotic-producingStreptomycesstrain JB140. The seven different competition experiments utilized three serial passages (three cycles of adaptation-selection of 15 days each) of a weak antibiotic-producingStreptomycesstrain (wild-type) against one (biculture) or two (triculture) or three (quadriculture) target pathogens. This resulted in the evolution of a weak antibiotic-producing strain into the seven unique mutant phenotypes that acquired the ability to constitutively exhibit increased antimicrobial activity against bacterial pathogens. The mutant not only effectively inhibited the growth of the tested pathogens but also observed to produce antimicrobial against multidrug-resistant (MDR)E. coli.Intriguingly, the highest antimicrobial activity was registered with theStreptomycesmutants that were adaptively evolved against the three pathogens (quadriculture competition). In contrast to the adaptively evolved mutants, a weak antimicrobial activity was detected in the un-evolved, wild-typeStreptomyces. To get molecular evidence of evolution, RAPD profiles of the wild-typeStreptomycesand its evolved mutants were compared that revealed significant polymorphism among them. These results demonstrated that competition-based adaptive laboratory evolution method can constitute a platform for evolutionary engineering to select improved phenotypes (mutants) with increased production of antibiotics against targeted pathogens.
Coiled coils 9-to-5: Rationalde novodesign of α-helical barrels with tunable oligomeric states
Authors: Dawson William M. , Martin Freddie J.O. , Rhys Guto G. , Shelley Kathryn L. , Brady R. Leo , Woolfson Derek N. 
Published: January 2021

ABSTRACTThe rational design of linear peptides that assemble controllably and predictably in water is challenging. Sequences must encode unique target structures and avoid alternative states. However, the stabilizing and discriminating non-covalent forces available are weak in water. Nonetheless, for α-helical coiled-coil assemblies considerable progress has been made in rationalde novodesign. In these, sequence repeats of nominally hydrophobic (h) and polar (p) residues,hpphppp, direct the assembly of amphipathic helices into dimeric to tetrameric bundles. Expanding this pattern tohpphhphcan produce larger α-helical barrels. Here, we show that pentamers to nonamers are achieved simply by varying the residue at one of thesehsites. In L/I-K-E-I-A-x-Z repeats, decreasing the size of Z from threonine to serine to alanine to glycine gives progressively larger oligomers. X-ray crystal structures of the resulting α-helical barrels rationalize this: side chains at Z point directly into the helical interfaces, and smaller residues allow closer helix contacts and larger assemblies.
Enrichment of Zα domains at cytoplasmic stress granules is due to their innate ability to bind nucleic acids
Authors: Gabriel Luisa , Srinivasan Bharath , Kuś Krzysztof , Mata João F. , Amorim Maria João , Jansen Lars E.T. , Athanasiadis Alekos 
Published: January 2021

AbstractZα domains are a subfamily of winged Helix-Turn-Helix (wHTH) domains found exclusively in proteins involved in the nucleic acids sensory pathway of vertebrate innate immune system and host evasion by viral pathogens. Interestingly, they are the only known protein domains that recognise the left-handed helical conformation of both dsDNA and dsRNA, known as Z-DNA and Z-RNA. Previously, it has been demonstrated that ADAR1 and ZBP1, two proteins possessing the Zα domains, localize to cytosolic stress granules. It was further speculated that such localization is principally mediated by Zα domains. To characterize and better understand such distinct and specific localization, we characterised thein vivointeractions and localization pattern for the amino terminal region of human DAI harbouring two Zα domains (ZαβDAI). Using immunoprecipitation and mass spectrometry, we identified several interacting partners that were components of the complex formed by Zα domains and RNAs. Differential interacting partners to wild-type Zα, relative to mutant proteins, demonstrated that most of the physiologically relevant interactions are mediated by the nucleic acid binding ability of the Zαβ. Further, we also show enrichment of selected complex components in cytoplasmic stress granules under conditions of stress. This ability is mostly lost in the mutants of ZαβDAI(ZαβDAI4×mut) that lack nucleic-acid binding ability. Thus, we posit that the mechanism for the translocation of Zα domain-containing proteins to stress granules is mainly mediated by the nucleic acid binding ability of their Zα domains. Finally, we demonstrate that FUS and PSF/p54nrb, two RNA binding proteins with established roles in stress granules, interact with Zα, which provides strong evidence for a role of these proteins in the innate immune system.
Systemic inflammation recruits fast-acting anti-inflammatory innate myeloid progenitors from BM into lymphatics
Authors: Serrano-Lopez Juana , Hegde Shailaja , Kumar Sachin , Serrano Josefina , Fang Jing , Wellendorf Ashley M. , Roche Paul A. , Rangel Yamileth , Carrington Léolène J. , Geiger Hartmut , Grimes H. Leighton , Luther Sanjiv , Maillard Ivan , Sanchez-Garcia Joaquin , Starczynowski Daniel T. , Cancelas Jose A. 
Published: January 2021

ABSTRACTInnate immune cellular effectors are actively consumed during systemic inflammation but the systemic traffic and the mechanisms that support their replenishment remain unknown. Here we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migration of granulocyte-macrophage progenitors and committed macrophage-dendritic progenitors, but not other progenitors or stem cells, from bone marrow (BM) to lymphatic capillaries. The progenitor traffic to the systemic lymphatic circulation is mediated by Ccl19/Ccr7 and is NFκB independent, Traf6/IκB-kinase/SNAP23 activation which is responsible for the secretion of pre-stored Ccl19 by a subpopulation of CD205+/CD172a+conventional dendritic cells type 2 (cDC2) and upregulation of BM myeloid progenitor Ccr7 signaling. The consequence of this progenitor traffic is anti-inflammatory with promotion of early survival and initiation of replenishment of lymph node cDC.