bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicity dependent photoresistance measurement vs. beam-shift thermal gradient
Authors: Yang Haozhe , Schmoranzerová Eva , Jang Pyunghwa , Nath Jayshankar , Guillet Thomas , Joumard Isabelle , Auffret Stéphane , Jamet Matthieu , Němec Petr , Gaudin Gilles , Miron Ioan-Mihai 
Published: November 2022

AbstractOptical detection techniques are among the most powerful methods used to characterize spintronic phenomena. The spin orientation can affect the light polarization, which, by the reciprocal mechanism, can modify the spin density. Numerous recent experiments, report local changes in the spin density induced by a circularly polarized focused laser beam. These effects are typically probed electrically, by detecting the variations of the photoresistance or photocurrent associated to the reversal of the light helicity. Here we show that in general, when the light helicity is modified, the beam profile is slightly altered, and the barycenter of the laser spot is displaced. Consequently, the temperature gradients produced by the laser heating will be modulated, producing thermo-electric signals that alternate in phase with the light polarization. These unintended signals, having no connection with the electron spin, appear under the same experimental conditions and can be easily misinterpreted. We show how this contribution can be experimentally assessed and removed from the measured data. We find that even when the beam profile is optimized, this effect is large, and completely overshadows the spin related signals in all the materials and experimental conditions that we have tested.
Low cost and massively parallel force spectroscopy with fluid loading on a chip
Authors: Akbari Ehsan , Shahhosseini Melika , Robbins Ariel , Poirier Michael G. , Song Jonathan W. , Castro Carlos E. 
Published: November 2022

AbstractCurrent approaches for single molecule force spectroscopy are typically constrained by low throughput and high instrumentation cost. Herein, a low-cost, high throughput technique is demonstrated using microfluidics for multiplexed mechanical manipulation of up to ~4000 individual molecules via molecular fluid loading on-a-chip (FLO-Chip). The FLO-Chip consists of serially connected microchannels with varying width, allowing for simultaneous testing at multiple loading rates. Molecular force measurements are demonstrated by dissociating Biotin-Streptavidin and Digoxigenin-AntiDigoxigenin interactions along with unzipping of double stranded DNA of varying sequence under different dynamic loading rates and solution conditions. Rupture force results under varying loading rates and solution conditions are in good agreement with prior studies, verifying a versatile approach for single molecule biophysics and molecular mechanobiology. FLO-Chip enables straightforward, rapid, low-cost, and portable mechanical testing of single molecules that can be implemented on a wide range of microscopes to broaden access and may enable new applications of molecular force spectroscopy.
Statistical inference links data and theory in network science
Authors: Peel Leto , Peixoto Tiago P. , De Domenico Manlio 
Published: November 2022

AbstractThe number of network science applications across many different fields has been rapidly increasing. Surprisingly, the development of theory and domain-specific applications often occur in isolation, risking an effective disconnect between theoretical and methodological advances and the way network science is employed in practice. Here we address this risk constructively, discussing good practices to guarantee more successful applications and reproducible results. We endorse designing statistically grounded methodologies to address challenges in network science. This approach allows one to explain observational data in terms of generative models, naturally deal with intrinsic uncertainties, and strengthen the link between theory and applications.
Integrase-mediated differentiation circuits improve evolutionary stability of burdensome and toxic functions in E. coli
Authors: Williams Rory L. , Murray Richard M. 
Published: November 2022

AbstractAdvances in synthetic biology, bioengineering, and computation allow us to rapidly and reliably program cells with increasingly complex and useful functions. However, because the functions we engineer cells to perform are typically burdensome to cell growth, they can be rapidly lost due to the processes of mutation and natural selection. Here, we show that a strategy of terminal differentiation improves the evolutionary stability of burdensome functions in a general manner by realizing a reproductive and metabolic division of labor. To implement this strategy, we develop a genetic differentiation circuit in Escherichia coli using unidirectional integrase-recombination. With terminal differentiation, differentiated cells uniquely express burdensome functions driven by the orthogonal T7 RNA polymerase, but their capacity to proliferate is limited to prevent the propagation of advantageous loss-of-function mutations that inevitably occur. We demonstrate computationally and experimentally that terminal differentiation increases duration and yield of high-burden expression and that its evolutionary stability can be improved with strategic redundancy. Further, we show this strategy can even be applied to toxic functions. Overall, this study provides an effective, generalizable approach for protecting burdensome engineered functions from evolutionary degradation.
The Neo-PLANET phase II trial of neoadjuvant camrelizumab plus concurrent chemoradiotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction
Authors: Tang Zhaoqing , Wang Yan , Liu Dan , Wang Xuefei , Xu Chen , Yu Yiyi , Cui Yuehong , Tang Cheng , Li Qian , Sun Jing , Zhang Qian , Ji Yuan , Ma Guifen , Li Haojie , Shen Zhenbin , Shen Kuntang , Zheng Rongrong , Hou Zhiguo , Liu Tianshu , Wang Jiping , Sun Yihong 
Published: November 2022

AbstractThe synergistic effect of neoadjuvant immunotherapy and chemoradiotherapy in gastric adenocarcinoma is unclear. This phase II trial (NCT03631615) investigated this neoadjuvant combination in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Thirty-six patients received capecitabine 850 mg/m2 twice daily and simultaneous radiotherapy for 5 weeks, sandwiched by a 21-day cycle of oxaliplatin 130 mg/m2 (day 1) plus capecitabine 1000 mg/m2 twice daily (days 1–14), respectively, followed by surgery. Camrelizumab 200 mg (day 1) was given for 5 cycles since initiating chemotherapy. Primary endpoint was pathological complete response (pCR, ypT0) rate. Secondary endpoints included total pCR (tpCR, ypT0N0) rate, major pathological response (MPR, < 10% residual tumor cells) rate, margin-free (R0) resection rate, downstaging, progression-free survival (PFS), overall survival (OS), and safety. The pCR rate was 33.3% (95% CI, 18.6–51.0), meeting pre-specified endpoint. TpCR, MPR, and R0 resection rates were 33.3%, 44.4%, and 91.7%, respectively. Twenty-eight (77.8%) patients reached ypN0. Two-year PFS and OS rates were 66.9% and 76.1%, respectively. The most common grade 3–4 adverse event was decreased lymphocyte count (27 [75.0%]). Neoadjuvant camrelizumab plus concurrent chemoradiotherapy exhibits promising pathological response in patients with locally advanced gastric adenocarcinoma, with an acceptable safety profile.
De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee
Authors: Liu Yunxi , Elworth R. A. Leo , Jochum Michael D. , Aagaard Kjersti M. , Treangen Todd J. 
Published: November 2022

AbstractComputational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low-biomass environments. Contamination from DNA extraction kits or sampling lab environments leaves taxonomic "bread crumbs" across multiple distinct sample types. Here we describe Squeegee, a de novo contamination detection tool that is based upon this principle, allowing the detection of microbial contaminants when negative controls are unavailable. On the low-biomass samples, we compare Squeegee predictions to experimental negative control data and show that Squeegee accurately recovers putative contaminants. We analyze samples of varying biomass from the Human Microbiome Project and identify likely, previously unreported kit contamination. Collectively, our results highlight that Squeegee can identify microbial contaminants with high precision and thus represents a computational approach for contaminant detection when negative controls are unavailable.
Lipidomic signatures align with inflammatory patterns and outcomes in critical illness
Authors: Wu Junru , Cyr Anthony , Gruen Danielle S. , Lovelace Tyler C. , Benos Panayiotis V. , Das Jishnu , Kar Upendra K. , Chen Tianmeng , Guyette Francis X. , Yazer Mark H. , Daley Brian J. , Miller Richard S. , Harbrecht Brian G. , Claridge Jeffrey A. , Phelan Herb A. , Zuckerbraun Brian S. , Neal Matthew D. , Johansson Pär I. , Stensballe Jakob , Namas Rami A. , Vodovotz Yoram , Sperry Jason L. , Billiar Timothy R. ,   PAMPer study group, Zenati Mazen S. , Brown Joshua B. , Triulzi Darrell J. , Young Barbara J. Early , Adams Peter W. , Alarcon Louis H. , Callaway Clifton W. , Forsythe Raquel M. , Yealy Donald M. , Peitzman Andrew B. , Buck Meghan L. , Ryman Ashley M. , Gimbel Elizabeth A. , Gilchrist Erin G. , Buhay Meghan , Chang Chung-Chou H. , Talisa Victor B. , Xu Tianyuan , Kalloway Kyle , Yates Andrew , Rawn Susan , Jenkins Judith M. , Trachtenberg Laura S. , Eden Randi K. , Fraifogl Joanne , Bates Craig , Howard Christina , Stebbins Cari , Witham William R. , McNeill Cathy , Putnam A. Tyler. , Snyder Amy , Ropp Jason , Duane Therese M. , Caliman Celeste , Beamon Mieshia 
Published: November 2022

AbstractAlterations in lipid metabolism have the potential to be markers as well as drivers of pathobiology of acute critical illness. Here, we took advantage of the temporal precision offered by trauma as a common cause of critical illness to identify the dynamic patterns in the circulating lipidome in critically ill humans. The major findings include an early loss of all classes of circulating lipids followed by a delayed and selective lipogenesis in patients destined to remain critically ill. The previously reported survival benefit of early thawed plasma administration was associated with preserved lipid levels that related to favorable changes in coagulation and inflammation biomarkers in causal modelling. Phosphatidylethanolamines (PE) were elevated in patients with persistent critical illness and PE levels were prognostic for worse outcomes not only in trauma but also severe COVID-19 patients. Here we show selective rise in systemic PE as a common prognostic feature of critical illness.
Ferritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still’s disease pathogenesis
Authors: Jia Jinchao , Wang Mengyan , Meng Jianfen , Ma Yuning , Wang Yang , Miao Naijun , Teng Jialin , Zhu Dehao , Shi Hui , Sun Yue , Liu Honglei , Cheng Xiaobing , Su Yutong , Ye Junna , Chi Huihui , Liu Tingting , Zhou Zhuochao , Wan Liyan , Chen Xia , Wang Fan , Zhang Hao , Ben Jingjing , Wang Jing , Yang Chengde , Hu Qiongyi 
Published: November 2022

AbstractHyperferritinemic syndrome, an overwhelming inflammatory condition, is characterized by high ferritin levels, systemic inflammation and multi-organ dysfunction, but the pathogenic role of ferritin remains largely unknown. Here we show in an animal model that ferritin administration leads to systemic and hepatic inflammation characterized by excessive neutrophil leukocyte infiltration and neutrophil extracellular trap (NET) formation in the liver tissue. Ferritin-induced NET formation depends on the expression of peptidylarginine deiminase 4 and neutrophil elastase and on reactive oxygen species production. Mechanistically, ferritin exposure increases both overall and cell surface expression of Msr1 on neutrophil leukocytes, and also acts as ligand to Msr1 to trigger the NET formation pathway. Depletion of neutrophil leukocytes or ablation of Msr1 protect mice from tissue damage and the hyperinflammatory response, which further confirms the role of Msr1 as ferritin receptor. The relevance of the animal model is underscored by the observation that enhanced NET formation, increased Msr1 expression and signalling on neutrophil leukocytes are also characteristic to adult-onset Still’s disease (AOSD), a typical hyperferritinemic syndrome. Collectively, our findings demonstrate an essential role of ferritin in NET-mediated cytokine storm, and suggest that targeting NETs or Msr1 may benefit AOSD patients.
Systematic characterization of cancer transcriptome at transcript resolution
Authors: Hu Wei , Wu Yangjun , Shi Qili , Wu Jingni , Kong Deping , Wu Xiaohua , He Xianghuo , Liu Teng , Li Shengli 
Published: November 2022

AbstractTranscribed RNAs undergo various regulation and modification to become functional transcripts. Notably, cancer transcriptome has not been fully characterized at transcript resolution. Herein, we carry out a reference-based transcript assembly across >1000 cancer cell lines. We identify 498,255 transcripts, approximately half of which are unannotated. Unannotated transcripts are closely associated with cancer-related hallmarks and show clinical significance. We build a high-confidence RNA binding protein (RBP)-transcript regulatory network, wherein most RBPs tend to regulate transcripts involved in cell proliferation. We identify numerous transcripts that are highly associated with anti-cancer drug sensitivity. Furthermore, we establish RBP-transcript-drug axes, wherein PTBP1 is experimentally validated to affect the sensitivity to decitabine by regulating KIAA1522-a6 transcript. Finally, we establish a user-friendly data portal to serve as a valuable resource for understanding cancer transcriptome diversity and its potential clinical utility at transcript level. Our study substantially extends cancer RNA repository and will facilitate anti-cancer drug discovery.
An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss
Authors: Asrani Kaushal , Woo Juhyung , Mendes Adrianna A. , Schaffer Ethan , Vidotto Thiago , Villanueva Clarence Rachel , Feng Kewen , Oliveira Lia , Murali Sanjana , Liu Hans B. , Salles Daniela C. , Lam Brandon , Argani Pedram , Lotan Tamara L. 
Published: November 2022

AbstractThe mechanistic target of rapamycin complex 1 (mTORC1) integrates inputs from growth factors and nutrients, but how mTORC1 autoregulates its activity remains unclear. The MiT/TFE transcription factors are phosphorylated and inactivated by mTORC1 following lysosomal recruitment by RagC/D GTPases in response to amino acid stimulation. We find that starvation-induced lysosomal localization of the RagC/D GAP complex, FLCN:FNIP2, is markedly impaired in a mTORC1-sensitive manner in renal cells with TSC2 loss, resulting in unexpected TFEB hypophosphorylation and activation upon feeding. TFEB phosphorylation in TSC2-null renal cells is partially restored by destabilization of the lysosomal folliculin complex (LFC) induced by FLCN mutants and is fully rescued by forced lysosomal localization of the FLCN:FNIP2 dimer. Our data indicate that a negative feedback loop constrains amino acid-induced, FLCN:FNIP2-mediated RagC activity in renal cells with constitutive mTORC1 signaling, and the resulting MiT/TFE hyperactivation may drive oncogenesis with loss of the TSC2 tumor suppressor.
Development and validation of self-monitoring auto-updating prognostic models of survival for hospitalized COVID-19 patients
Authors: Levy Todd J. , Coppa Kevin , Cang Jinxuan , Barnaby Douglas P. , Paradis Marc D. , Cohen Stuart L. , Makhnevich Alex , van Klaveren David , Kent David M. , Davidson Karina W. , Hirsch Jamie S. , Zanos Theodoros P. 
Published: November 2022

AbstractClinical prognostic models can assist patient care decisions. However, their performance can drift over time and location, necessitating model monitoring and updating. Despite rapid and significant changes during the pandemic, prognostic models for COVID-19 patients do not currently account for these drifts. We develop a framework for continuously monitoring and updating prognostic models and apply it to predict 28-day survival in COVID-19 patients. We use demographic, laboratory, and clinical data from electronic health records of 34912 hospitalized COVID-19 patients from March 2020 until May 2022 and compare three modeling methods. Model calibration performance drift is immediately detected with minor fluctuations in discrimination. The overall calibration on the prospective validation cohort is significantly improved when comparing the dynamically updated models against their static counterparts. Our findings suggest that, using this framework, models remain accurate and well-calibrated across various waves, variants, race and sex and yield positive net-benefits.
Maprotiline restores ER homeostasis and rescues neurodegeneration via Histamine Receptor H1 inhibition in retinal ganglion cells
Authors: Chen Wei , Liu Pingting , Liu Dong , Huang Haoliang , Feng Xue , Fang Fang , Li Liang , Wu Jian , Liu Liang , Solow-Cordero David E. , Hu Yang 
Published: November 2022

AbstractWhen the protein or calcium homeostasis of the endoplasmic reticulum (ER) is adversely altered, cells experience ER stress that leads to various diseases including neurodegeneration. Genetic deletion of an ER stress downstream effector, CHOP, significantly protects neuron somata and axons. Here we report that three tricyclic compounds identified through a small-scale high throughput screening using a CHOP promoter-driven luciferase cell-based assay, effectively inhibit ER stress by antagonizing their common target, histamine receptor H1 (HRH1). We further demonstrated that systemic administration of one of these compounds, maprotiline, or CRISPR-mediated retinal ganglion cell (RGC)-specific HRH1 inhibition, delivers considerable neuroprotection of both RGC somata and axons and preservation of visual function in two mouse optic neuropathy models. Finally, we determine that maprotiline restores ER homeostasis by inhibiting HRH1-mediated Ca2+ release from ER. In this work we establish maprotiline as a candidate neuroprotectant and HRH1 as a potential therapeutic target for glaucoma.
Rare and common genetic determinants of metabolic individuality and their effects on human health
Authors: Surendran Praveen , Stewart Isobel D. , Au Yeung Victoria P. W. , Pietzner Maik , Raffler Johannes , Wörheide Maria A. , Li Chen , Smith Rebecca F. , Wittemans Laura B. L. , Bomba Lorenzo , Menni Cristina , Zierer Jonas , Rossi Niccolò , Sheridan Patricia A. , Watkins Nicholas A. , Mangino Massimo , Hysi Pirro G. , Di Angelantonio Emanuele , Falchi Mario , Spector Tim D. , Soranzo Nicole , Michelotti Gregory A. , Arlt Wiebke , Lotta Luca A. , Denaxas Spiros , Hemingway Harry , Gamazon Eric R. , Howson Joanna M. M. , Wood Angela M. , Danesh John , Wareham Nicholas J. , Kastenmüller Gabi , Fauman Eric B. , Suhre Karsten , Butterworth Adam S. , Langenberg Claudia 
Published: November 2022

AbstractGarrod’s concept of ‘chemical individuality’ has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant–metabolite associations (P < 1.25 × 10−11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant–metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships.
Acute and postacute sequelae associated with SARS-CoV-2 reinfection
Authors: Bowe Benjamin , Xie Yan , Al-Aly Ziyad 
Published: November 2022

AbstractFirst infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risk of acute and postacute death and sequelae in various organ systems. Whether reinfection adds to risks incurred after first infection is unclear. Here we used the US Department of Veterans Affairs’ national healthcare database to build a cohort of individuals with one SARS-CoV-2 infection (n = 443,588), reinfection (two or more infections, n = 40,947) and a noninfected control (n = 5,334,729). We used inverse probability-weighted survival models to estimate risks and 6-month burdens of death, hospitalization and incident sequelae. Compared to no reinfection, reinfection contributed additional risks of death (hazard ratio (HR) = 2.17, 95% confidence intervals (CI) 1.93–2.45), hospitalization (HR = 3.32, 95% CI 3.13–3.51) and sequelae including pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders. The risks were evident regardless of vaccination status. The risks were most pronounced in the acute phase but persisted in the postacute phase at 6 months. Compared to noninfected controls, cumulative risks and burdens of repeat infection increased according to the number of infections. Limitations included a cohort of mostly white males. The evidence shows that reinfection further increases risks of death, hospitalization and sequelae in multiple organ systems in the acute and postacute phase. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.