bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative Outcomes of Closed Versus Nonclosed Mesentery Laparoscopic Colectomy: A Retrospective Single-center Study
Authors: Nitta Takeo , Ebihara Yuma , Hirano Satoshi 
Published: June 2021

Purpose:
This study aimed to clarify the clinical significance of closing the mesenteric defect in laparoscopic colectomy.

Materials and Methods:
We retrospectively evaluated 369 patients who underwent left-sided or right-sided resection via laparoscopic colectomy at our institute. Patients were stratified by open versus closed handling of the mesenteric defect. The perioperative clinical factors, surgical maneuvers, and postoperative complications were statistically analyzed.

Results:
No significant intergroup differences were found in the perioperative clinical factors or surgical maneuvers except for number of days to the first soft diet (P=0.0214) and postoperative complications (P=0.0379). Among the postoperative complications, only ileus occurred more frequently in the closed group than in the open group (P=0.0227).

Conclusions:
This study revealed that closure of the mesenteric defect following laparoscopic colectomy might be associated with an increased incidence of postoperative ileus.
Critical decisions in the trauma intensive care unit: Are we practicing primary palliative care?
Authors: Edsall Andrew , Howard Shannon , Dewey Elizabeth N. , Siegel Timothy , Zonies David , Brasel Karen , Cook Mackenzie R. , Nagengast Andrea K. 
Published: June 2021

BACKGROUND
Devastating injuries require both urgent assessment by a trauma service and early attention to patients’ goals of care (GOC). American College of Surgeons Trauma Quality Improvement Program (TQIP) guidelines recommend an initial palliative assessment within 24 hours of admission and family meeting, if needed, within 72 hours. We hypothesize that a primary palliative care–based practice improves adherence to TQIP guidelines in trauma patients.

METHODS
All adult trauma patients who died while inpatient from January 2014 to December 2018 were reviewed. Timing of GOC discussions, transition to comfort measures only (CMO), and the utilization of specialty palliative services were analyzed with univariate analysis.

RESULTS
During the study period, 415 inpatients died. Median Injury Severity Score was 26 (interquartile range [IQR], 17–34), median age was 67 years (IQR, 51–81 years), and 72% (n = 299) transitioned to CMO before death. Documented GOC discussions increased from 77% of patients in 2014 to 95% of patients in 2018 (p < 0.001), and in 2018, the median time to the first GOC discussion was 15 hours (IQR, 7– 24 hours). Specialty palliative care was consulted in 7% of all patients. Of patients who had at least one GOC discussion, 98% were led by the trauma intensive care unit (TICU) team. Median time from admission to first GOC discussion was 27 hours (IQR, 6–91 hours). Median number of GOC discussions was 1 (IQR, 1–2). Median time to CMO after the final GOC discussion was 0 hours (IQR, 0–3). Median time to death after transition to CMO was 4 hours (IQR, 1–18 hours).

CONCLUSION
Of those who died during index admission, we demonstrated significant improvement in adherence to American College of Surgeons TQIP palliative guidelines across the 5-year study period, with the TICU team guiding the majority of GOC discussions. Our TICU team has developed an effective primary palliative care approach, selectively consulting specialty palliative care only when needed.

LEVEL OF EVIDENCE
Therapeutic/care management, level III.
Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection
Authors: Feng Shuo , Phillips Daniel J. , White Thomas , Sayal Homesh , Aley Parvinder K. , Bibi Sagida , Dold Christina , Fuskova Michelle , Gilbert Sarah C. , Hirsch Ian , Humphries Holly E. , Jepson Brett , Kelly Elizabeth J. , Plested Emma , Shoemaker Kathryn , Thomas Kelly M. , Vekemans Johan , Villafana Tonya L. , Lambe Teresa , Pollard Andrew J , Voysey Merryn ,   the Oxford COVID Vaccine Trial Group
Published: June 2021

AbstractBackgroundAlthough 6 COVID-19 vaccines have been approved by the World Health Organisation as of 16th June 2021, global supply remains limited. An understanding of the immune response associated with protection could facilitate rapid licensure of new vaccines.MethodsData from a randomised efficacy trial of ChAdOx1 nCoV-19 (AZD1222) vaccine in the UK was analysed to determine the antibody levels associated with protection against SARS-CoV-2. Anti-spike and anti-RBD IgG by multiplex immunoassay, pseudovirus and live neutralising antibody at 28 days after the second dose were measured in infected and non-infected vaccine recipients. Weighted generalised additive models for binary data were applied to symptomatic and asymptomatic SARS-CoV-2 infection data from ChAdOx1 nCoV-19 recipients. Cubic spline smoothed log antibody levels, and weights were applied to account for potential selection bias in sample processing. Models were adjusted for baseline risk of exposure to SARS-CoV-2 infection.ResultsHigher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Vaccine efficacy of 80% against primary symptomatic COVID-19 was achieved with an antibody level of 40923 (95% CI: 16748, 125017) and 63383 (95% CI: 16903, not computed (NC)) for anti-spike and anti-RBD, and 185 (95% CI: NC, NC) and 247 (95% CI: 101, NC) for pseudo- and live-neutralisation assays respectively. Antibody responses did not correlate with overall protection against asymptomatic infection.ConclusionsCorrelates of protection can be used to bridge to new populations using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where large efficacy trials cannot be conducted. More work is needed to assess correlates for emerging variants.
Dystrophin regulates peripheral circadian SRF signalling
Authors: Betts Corinne A , Jagannath Aarti , van Westering Tirsa LE , Bowerman Melissa , Banerjee Subhashis , Meng Jinhong , Falzarano Maria Sofia , Cravo Lara , McClorey Graham , Meijboom Katharina E , Bhomra Amarjit , Lim Wooi Fang , Rinaldi Carlo , Counsell John R , Chwalenia Katarzyna , O’Donovan Elizabeth , Saleh Amer F , Gait Michael J , Morgan Jennifer E , Ferlini Alessandra , Foster Russell G , Wood Matthew JA 
Published: June 2021

AbstractDystrophin is a sarcolemmal protein essential for muscle contraction and maintenance, absence of which leads to the devastating muscle wasting disease Duchenne muscular dystrophy (DMD)[1, 2]. Dystrophin has an actin-binding domain [3–5], which specifically binds and stabilises filamentous (F)-actin[6], an integral component of the RhoA-actin-serum response factor (SRF)-pathway[7]. The RhoA-actin-SRF-pathway plays an essential role in circadian signalling whereby the hypothalamic suprachiasmatic nucleus, transmits systemic cues to peripheral tissues, activating SRF and transcription of clock target genes[8, 9]. Given dystrophin binds F-actin and disturbed SRF-signalling disrupts clock entrainment, we hypothesised that dystrophin loss causes circadian deficits. Here we show for the first time alterations in the RhoA-actin-SRF-signalling-pathway, in both dystrophin-deficient myotubes and dystrophic mouse models. Specifically, we demonstrate reduced F/G-actin ratios and nuclear MRTF, dysregulation of core clock and downstream target-genes, and down-regulation of key circadian genes in muscle biopsies from DMD patients harbouring an array of mutations. Further, disrupted circadian locomotor behaviour was observed in dystrophic mice indicative of disrupted SCN signalling, and indeed dystrophin protein was absent in the SCN of dystrophic animals. Dystrophin is thus a critically important component of the RhoA-actin-SRF-pathway and a novel mediator of circadian signalling in peripheral tissues, loss of which leads to circadian dysregulation.
utR.annotation: a tool for annotating genomic variants that could influence post-transcriptional regulation
Authors: Liu Yating , Dougherty Joseph D. 
Published: June 2021

AbstractSummaryWhole genome sequencing of patient populations is identifying thousands of new variants in UnTranslated Regions(UTRs). While the consequences of UTR mutations are not as easily predicted from primary sequence as coding mutations are, there are some known features of UTRs modulate their function. utR.annotation is an R package that can be used to annotate potential deleterious variants in the UTR regions for both human and mouse species. Given a CSV or VCF format variant file, utR.annotation provides information of each variant on whether and how it alters known translational regulators including:upstream Open Reading Frames (uORFs), upstream Kozak sequences, polyA signals, the Kozak sequence at the annotated translation initiation site, start codon, and stop codon, conservation scores in the variant position, and whether and how it changes ribosome loading based on a model from empirical data.Availability and implementationutR.annotation is freely available on Bitbucket (https://bitbucket.org/jdlabteam/utr.annotation/src/master/) and CRAN (to be updated)Supplementary informationSupplementary data are available athttps://wustl.box.com/s/yye99bryfin89nav45gv91l5k35fxo7z
Integrative COVID-19 Biological Network Inference with Probabilistic Core Decomposition
Authors: Guo Yang , Esfahani Fatemeh , Shao Xiaojian , Srinivasan Venkatesh , Thomo Alex , Xing Li , Zhang Xuekui 
Published: June 2021

AbstractThe SARS-CoV-2 coronavirus is responsible for millions of deaths around the world. To help contribute to the understanding of crucial knowledge and to further generate new hypotheses relevant to SARS-CoV-2 and human protein interactions, we make use of the information abundant Biomine probabilistic database and extend the experimentally identified SARS-CoV-2-human protein-protein interaction (PPI) networkin silico. We generate an extended network by integrating information from the Biomine database, the PPI network, and other experimentally validated results. To generate novel hypotheses, we focus on the high-connectivity sub-communities that overlap most with the integrated experimentally validated results in the extended network. Therefore, we propose a new data analysis pipeline that can efficiently compute core decomposition on the extended network and identify dense subgraphs. We then evaluate the identified dense subgraph and the generated hypotheses in three contexts: literature validation for uncovered virus targeting genes and proteins, gene function enrichment analysis on subgraphs, and literature support on drug repurposing for identified tissues and diseases related to COVID-19. The majority types of the generated hypotheses are proteins with their encoding genes and we rank them by sorting their connections to the integrated experimentally validated nodes. In addition, we compile a comprehensive list of novel genes, and proteins potentially related to COVID-19, as well as novel diseases which might be comorbidities. Together with the generated hypotheses, our results provide novel knowledge relevant to COVID-19 for further validation.
Aliquoting of isobaric labeling reagents for low concentration and single cell proteomics samples
Authors: Yuan Yuting , Orsburn Benjamin C. 
Published: June 2021

AbstractThe introduction of isobaric tagging reagents enabled more accurate, high-throughput quantitative proteomics by enabling multiple samples to be multiplexed. One drawback of these workflows is the relative expense of the proprietary isobaric reagents, which is often only second to the expense of the instruments themselves. These highly reactive chemical tags are only commercially available in relatively large aliquots compared to the typical amounts of peptides analyzed in proteomic workflows today. Excess reagents are typically disposed of following a single labeling experiment or those performed within a few days of opening a new kit. We present a simple procedure to aliquot commercial isobaric tagging reagents and demonstrate the successful and high efficiency labeling of multiple samples over a period of six months. The samples presented herein were selected as the most diverse ones labeled by prepared aliquots from a single labeling reagent kit over this period. We observe comparable labeling efficiency from 100 microgram to 100 picograms of peptide when labeling samples from both human digest standards, cancer cell lines prepared in-house and from cells directly obtained from human organ donors, despite differences in cell type, lysis, and digestion procedures. No labeling experiment of whole human proteomics samples achieved less than 92% labeling efficiency over this period. When preparing phosphoproteomic samples 6 months after the date of the aliquoting procedure, we observed a decrease in labeling efficiency to approximately 86%, indicating the end of the useful lifetime of aliquots prepared in this manner. Over this period, we have effectively reduced the reagent costs of each experiment to less than 10% of the predicted costs when following the manufacturer instructions for use and disposal. While aliquoting of reagents can be performed by hand, we provide a complete template for automatic aliquoting using an affordable liquid handling robot, including plans for 3D printing of two parts we have found useful for streamlining this procedure.Abstract Graphic
A TREM2-derived circRNA is upregulated in the entorhinal cortex of Alzheimer’s disease patients
Authors: Urdánoz-Casado Amaya , Gordoa Javier Sánchez-Ruiz de , Robles Maitane , Roldan Miren , Zelaya María Victoria , Blanco-Luquin Idoia , Mendioroz Maite 
Published: June 2021

AbstractCircular RNAs (circRNAs) are a novel class of noncoding RNAs characterized by a covalent and stable closed loop structure. circRNAs are enriched in neural tissues, particularly at synapses, where they are involved in synaptic plasticity. Alzheimer’s disease (AD) is considered a synaptopathy since neurodegeneration causes loss or dysfunction of synapses. Microglia participate in synaptic pruning and also play a crucial role in developing AD. For instance, genetic variants in TREM2, a microglia-related gene, are risk factors for AD. Alterations in circRNAs expression have been described in different neurological diseases, including AD. However, no TREM2-derived circRNAs have been described so far. TREM2 has 3 linear RNA variants due to alternative splicing. We hypothesized that alternative splicing of exon 4 might be favoring circRNAs originating from TREM2 (circTREM2s), which in turn might be involved in AD pathogenesis. First, divergent primers (overlapping exons 3-4 and 4-5) were designed to amplify circRNAs by RT-PCR, which were confirmed by Sanger sequencing. Three candidate TREM2-derived circRNAs were identified on control human entorhinal samples. Then, additional primer sets were used to confirm back-splicing junctions. One of the circRNAs, circTREM2_1, was consistently amplified with all primer sets. In addition, circTREM2_1 was also present in AD entorhinal cortex samples and in HMC3 cells. We observed that circTREM2_1 is up-regulated in AD entorhinal cortex samples compared to controls, particularly at early stages of the disease, when we performed RT-qPCR. In conclusion, we have identified a novel circRNA derived from the TREM2 gene that could play a role in AD pathogenesis.
Prolonged and distributed processing of facial identity in the human brain
Authors: Stecher Rico , Muukkonen Ilkka , Salmela Viljami , Rostalski Sophie-Marie , Ambrus Géza Gergely , Kovács Gyula 
Published: June 2021

AbstractThe recognition of facial identity is essential for social interactions. Despite extensive prior fMRI and EEG/MEG research on the neural representations of familiar faces, we know little about the spatio-temporal dynamics of face identity information. Therefore, we applied a novel multimodal approach by fusing the neuronal responses recorded in an fMRI and an EEG experiment. We analyzed the neural responses to naturally varying famous faces and traced how face identity emerges over time in different areas of the brain. We found that image invariant face identity information prevails over an extended time period (from 150 to 810 ms after stimulus onset) in the representational geometry of a broadly distributed network of parietal, temporal, and frontal areas with overlapping temporal profiles. These results challenge the current hierarchical models of face perception and suggest instead concerted and parallel activation of multiple nodes in the brain’s identity coding network while processing information of familiar faces.
Dopamine Neurons Evaluate Natural Fluctuations in Performance Quality
Authors: Duffy Alison , Latimer Kenneth W. , Goldberg Jesse H. , Fairhall Adrienne L. , Gadagkar Vikram 
Published: June 2021

SUMMARYMany motor skills are learned by comparing ongoing behavior to internal performance benchmarks. Dopamine neurons encode performance error in behavioral paradigms where error is externally induced, but it remains unknown if dopamine also signals the quality of natural performance fluctuations. Here we recorded dopamine neurons in singing birds and examined how spontaneous dopamine spiking activity correlated with natural fluctuations in ongoing song. Antidromically identified basal ganglia-projecting dopamine neurons correlated with recent, and not future, song variations, consistent with a role in evaluation, not production. Furthermore, dopamine spiking was suppressed following the production of outlying vocal variations, consistent with a role for active song maintenance. These data show for the first time that spontaneous dopamine spiking can evaluate natural behavioral fluctuations unperturbed by experimental events such as cues or rewards.
MethodsJ2: A Software Tool to Improve Microscopy Methods Reporting
Authors: Ryan Joel , Pengo Thomas , Rigano Alex , Llopis Paula Montero , Itano Michelle S. , Cameron Lisa , Marqués Guillermo , Strambio-De-Castillia Caterina , Sanders Mark A. , Brown Claire M. 
Published: June 2021

ABSTRACTProper reporting of metadata is essential to reproduce microscopy experiments, interpret results and share images. Experimental scientists can report details about sample preparation and imaging conditions while imaging scientists have the expertise required to collect and report the image acquisition, hardware and software metadata information. MethodsJ2 is an ImageJ/Fiji based software tool that gathers metadata and automatically generates text for the methods section of publications.
Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength
Authors: Kong Jennifer H. , Young Cullen B. , Pusapati Ganesh V. , Espinoza F Hernán , Patel Chandni B. , Beckert Francis , Ho Sebastian , Patel Bhaven B. , Gabriel George C. , Aravind L. , Bazan J Fernando , Gunn Teresa M. , Lo Cecilia W. , Rohatgi Rajat 
Published: June 2021

SUMMARYBirth defects result from interactions between genetic and environmental factors, but the mechanisms remain poorly understood. We find that mutations and teratogens interact in predictable ways to cause birth defects by changing target cell sensitivity to Hedgehog (Hh) ligands. These interactions converge on a membrane protein complex, the MMM complex, that promotes degradation of the Hh transducer Smoothened (SMO). Deficiency of the MMM component MOSMO results in elevated SMO and increased Hh signaling, causing multiple birth defects. In utero exposure to a teratogen that directly inhibits SMO reduces the penetrance and expressivity of birth defects in Mosmo-/- embryos. Additionally, tissues that develop normally in Mosmo-/- embryos are refractory to the teratogen. Thus, changes in the abundance of the protein target of a teratogen can change birth defect outcomes by quantitative shifts in Hh signaling. Consequently, small molecules that re-calibrate signaling strength could be harnessed to rescue structural birth defects.
Sulfation of glycosaminoglycans depends on catalytic activity of a lithium-inhibited phosphatase
Authors: Eisele Brynna S. , Luka Zigmund A. , Wu Alice J. , Yang Fei , Hale Andrew T. , York John D. 
Published: June 2021

AbstractGolgi-resident bisphosphate nucleotidase 2 (BPNT2) is a member of a family of magnesium-dependent/lithium-inhibited phosphatases that share a three-dimensional structural motif that directly coordinates metal binding to effect phosphate hydrolysis. BPNT2 is responsible for the breakdown of 3’-phosphoadenosine-5’-phosphate (PAP), a by-product of glycosaminoglycan (GAG) sulfation. Disruption of BPNT2 in mice leads to skeletal abnormalities due to impaired GAG sulfation, especially chondroitin-4-sulfation. Mutations in BPNT2 have also been found to underlie a chondrodysplastic disorder in humans. The precise mechanism by which loss of BPNT2 impairs sulfation remains unclear. Here, we utilize an in vitro approach using mouse embryonic fibroblasts (MEFs) to test the hypothesis that catalytic activity of BPNT2 is required for GAG sulfation. We show that a catalytic-dead Bpnt2 construct (D108A) does not rescue impairments in intracellular or secreted sulfated GAG, including decreased chondroitin-4-sulfate, present in Bpnt2-knockout MEFs. We also demonstrate that missense mutations in Bpnt2 which are adjacent to the catalytic site (and known to cause chondrodysplasia in humans) recapitulate defects in overall GAG sulfation and chondroitin-4-sulfation in MEF cultures. We further show that treatment of MEFs with lithium inhibits GAG sulfation, and that this effect depends on the presence of BPNT2. This work demonstrates that the catalytic activity of an enzyme potently inhibited by lithium can modulate GAG sulfation and therefore extracellular matrix composition, revealing new insights into lithium pharmacology and the pathophysiology of psychiatric disorders responsive to lithium.
Predictors of behavioral intention to adopt e-AgriFinance app among the farmers in Sarawak, Malaysia
Authors: Omar Quistina , Yap Ching Seng , Ho Poh Ling , Keling William 
Published: June 2021

PurposeThis study examines the predictors of behavioral intention of farmers to adopt a mobile agricultural finance application called e-AgriFinance using the Unified Theory of Acceptance and Use of Technology (UTAUT) and perceived cost as an additional predictor.Design/methodology/approachUsing a questionnaire survey, data are collected from 337 farmers in Sarawak, Malaysia. The collected data are analyzed using partial least squares structural equation modelling (PLS-SEM).FindingsThe research finds that performance expectancy, effort expectancy, social influence and facilitating conditions are positively related to behavioral intention to adopt the e-AgriFinance app, with social influence being the strongest predictor. Perceived cost is also found to be positively related to behavioral intention which contradicts the prediction of the model.Research limitations/implicationsThis study contributes to the use of UTAUT in predicting the adoption of mobile agricultural finance applications among farmers.Practical implicationsFor practice, this study provides implications for the Sarawak government to promote digital and financial inclusivity for all communities. This study also provides insights into important features of the e-AgriFinance app for digital finance providers to develop the apps that will be well accepted by farmers in the future.Originality/valueThis research is one of the few studies that focused on farmers' mobile technology adoption in agribusiness from the perspective of an emerging economy.