bluuebunny/crossref_metadata_2025_split huggingface dataset:
Archaeal pseudomurein and bacterial murein cell wall biosynthesis share a common evolutionary ancestry
Authors: Subedi Bishwa P , Martin William F , Carbone Vincenzo , Duin Eduardus C , Cronin Bryan , Sauter Julia , Schofield Linley R , Sutherland-Smith Andrew J , Ronimus Ron S 
Published: August 2021

ABSTRACTBacteria near-universally contain a cell wall sacculus of murein (peptidoglycan), the synthesis of which has been intensively studied for over 50 years. In striking contrast, archaeal species possess a variety of other cell wall types, none of them closely resembling murein. Interestingly though, one type of archaeal cell wall termed pseudomurein found in the methanogen orders Methanobacteriales and Methanopyrales is a structural analogue of murein in that it contains a glycan backbone that is cross-linked by a L-amino acid peptide. Here, we present taxonomic distribution, gene cluster and phylogenetic analyses that confirm orthologues of 13 bacterial murein biosynthesis enzymes in pseudomurein-containing methanogens, most of which are distantly related to their bacterial counterparts. We also present the first structure of an archaeal pseudomurein peptide ligase from Methanothermus fervidus DSM1088 (Mfer336) to a resolution of 2.5 Å and show that it possesses a similar overall tertiary three domain structure to bacterial MurC and MurD type murein peptide ligases. Taken together the data strongly indicate that murein and pseudomurein biosynthetic pathways share a common evolutionary history.
LD-CNV: rapid and simple discovery of chromosomal translocations using linkage disequilibrium between copy number variable loci
Authors: Comai Luca , Amundson Kirk R , Ordoñez Benny , Zhao Xin , Braz Guilherme Tomaz , Jiang Jiming , Henry Isabelle M 
Published: August 2021

AbstractLarge-scale structural variations, such as chromosomal translocations, can have profound effects on fitness and phenotype, but are difficult to identify and characterize. Here, we describe a simple and effective method aimed at identifying translocations using only the dosage of sequence reads mapped on the reference genome. We binned reads on genomic segments sized according to sequencing coverage and identified instances when copy number segregated in populations. For each dosage-polymorphic 1 Mb bin, we tested independence, effectively an apparent linkage disequilibrium (LD), with other variable bins. In nine potato (Solanum tuberosum) dihaploid families translocations affecting pericentromeric regions were common and in two cases were due to genomic misassembly. In two populations, we found evidence for translocation affecting euchromatic arms. In cv. PI 310467, a nonreciprocal translocation between chromosomes (chr.) 7 and 8 resulted in a 5–3 copy number change affecting several Mb at the respective chromosome tips. In cv. “Alca Tarma,” the terminal arm of chr. 4 translocated to the tip of chr. 1. Using oligonucleotide-based fluorescent in situ hybridization painting probes (oligo-FISH), we tested and confirmed the predicted arrangement in PI 310467. In 192 natural accessions of Arabidopsis thaliana, dosage haplotypes tended to vary continuously and resulted in higher noise, while apparent LD between pericentromeric regions suggested the effect of repeats. This method, LD-CNV, should be useful in species where translocations are suspected because it tests linkage without the need for genotyping.
Association of Circulating Fibrocytes With Fibrostenotic Small Bowel Crohn’s Disease
Authors: Ueno Aito , Jijon Humberto B , Peng Richard , Sparksman Steven , Mainoli Barbara , Filyk Alexis , Li Yan , Wilson Stephanie , Novak Kerri , Panaccione Remo , Hirota Simon , Dufour Antoine , Lu Cathy , Beck Paul L 
Published: August 2021

AbstractBackgroundFibrocytes are hematopoietic cells with features of mesenchymal cells found in the circulation and inflammatory sites implicated in promoting fibrosis in many fibroinflammatory diseases. However, their role(s) in the development of intestinal fibrosis is poorly understood. Here, we investigated a potential role of fibrocytes in the development of fibrosis in Crohn’s disease (CD) and sought factors that may impact their development and function.MethodsPlasma and mononuclear cells were collected from patients with and without fibrostenotic CD. Fibrocytes defined as CD11b+, CD34+, and Collagen 1+ were correlated with clinical assessments of fibrosis, including evaluation using intestinal ultrasound. We measured the levels of relevant circulating molecules via Luminex and studied the effect of patient plasma proteins on fibrocyte differentiation.ResultsFibrocyte numbers were increased in CD patients with stricturing Crohn’s disease compared with patients with an inflammatory phenotype (P = .0013), with strong correlation between fibrocyte numbers and acoustic radiation force impulse (ARFI), a measure of bowel elasticity on intestinal ultrasound (R = .8383, P = .0127). Fibrostenotic plasma was a more potent inducer of fibrocyte differentiation in both primary human monocytes and cell line and contained increased levels of cytokines implicated in fibrocyte differentiation compared with plasma from inflammatory patients. Interestingly, increased fibrocyte numbers at time of ultrasound were associated with escalation of medical therapy and endoscopic/surgical management of small bowel strictures at 30 months follow-up.ConclusionsCirculating fibrocytes strongly correlate with fibrostenotic disease in CD, and they may serve as predictors for escalation of medical +/- surgical therapy.
Antitumor Necrosis Factor-like Ligand 1A Therapy Targets Tissue Inflammation and Fibrosis Pathways and Reduces Gut Pathobionts in Ulcerative Colitis
Authors: Hassan-Zahraee Mina , Ye Zhan , Xi Li , Baniecki Mary Lynn , Li Xingpeng , Hyde Craig L , Zhang Jenny , Raha Nancy , Karlsson Fridrik , Quan Jie , Ziemek Daniel , Neelakantan Srividya , Lepsy Christopher , Allegretti Jessica R , Romatowski Jacek , Scherl Ellen J , Klopocka Maria , Danese Silvio , Chandra Deepa E , Schoenbeck Uwe , Vincent Michael S , Longman Randy , Hung Kenneth E 
Published: August 2021

AbstractBackgroundThe first-in-class treatment PF-06480605 targets the tumor necrosis factor-like ligand 1A (TL1A) molecule in humans. Results from the phase 2a TUSCANY trial highlighted the safety and efficacy of PF-06480605 in ulcerative colitis. Preclinical and in vitro models have identified a role for TL1A in both innate and adaptive immune responses, but the mechanisms underlying the efficacy of anti-TL1A treatment in inflammatory bowel disease (IBD) are not known.MethodsHere, we provide analysis of tissue transcriptomic, peripheral blood proteomic, and fecal metagenomic data from the recently completed phase 2a TUSCANY trial and demonstrate endoscopic improvement post-treatment with PF-06480605 in participants with ulcerative colitis.ResultsOur results revealed robust TL1A target engagement in colonic tissue and a distinct colonic transcriptional response reflecting a reduction in inflammatory T helper 17 cell, macrophage, and fibrosis pathways in patients with endoscopic improvement. Proteomic analysis of peripheral blood revealed a corresponding decrease in inflammatory T-cell cytokines. Finally, microbiome analysis showed significant changes in IBD-associated pathobionts, Streptococcus salivarius, S. parasanguinis, and Haemophilus parainfluenzae post-therapy.ConclusionsThe ability of PF-06480605 to engage and inhibit colonic TL1A, targeting inflammatory T cell and fibrosis pathways, provides the first-in-human mechanistic data to guide anti-TL1A therapy for the treatment of IBD.
Risk Factors for Postpartum Disease Activity in Women With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
Authors: Malhi Gurpreet , Tandon Parul , Perlmutter Jonah Wiseman , Nguyen Geoffrey , Huang Vivian 
Published: August 2021

Abstract

Background
Women with inflammatory bowel disease (IBD) have an increased risk of postpartum disease activity. We aimed to systematically determine the effect of various risk factors on postpartum IBD disease activity.

Methods
Electronic databases were searched through January 2021 for studies that reported risk of postpartum disease activity in women with IBD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the impact of IBD phenotype, disease activity, therapy de-escalation, mode of delivery, and breastfeeding on postpartum disease activity. Study bias was determined using the Quality in Prognostic Studies tool.

Results
Twenty-seven observational studies (3825 patients) were included, 15 of which had a high risk of confounding bias. The pooled incidence of women with postpartum active IBD was 31.9% (95% CI, 25.6–38.1). Similar results were seen with ulcerative colitis and Crohn’s disease (CD; OR, 0.96; 95% CI, 0.58–1.59). Those with stricturing (OR, 3.64; 95% CI, 1.31–10.08) and penetrating (OR, 4.25; 95% CI, 1.11–16.26) CD had higher odds of postpartum active IBD. Active disease at conception (OR, 10.59; 95% CI, 1.48–76.02) and during pregnancy (OR, 4.91; 95% CI, 1.82–13.23) increased the odds of postpartum disease activity. Similarly, biologic discontinuation in the third trimester (OR, 1.77; 95% CI, 1.01–3.10) and therapy de-escalation after delivery (OR, 7.36; 95% CI, 3.38–16.0) was associated with postpartum disease activity.

Conclusions
Complicated Crohn’s disease, disease activity at conception and during pregnancy, and de-escalation of biologics during pregnancy or after delivery are associated with postpartum disease activity in women with IBD.
Smooth Fano Intrinsic Grassmannians of Type 2,n with Picard Number Two
Authors: Qureshi Muhammad Imran , Wrobel Milena 
Published: August 2021

AbstractWe introduce the notion of intrinsic Grassmannians that generalizes the well-known weighted Grassmannians. An intrinsic Grassmannian is a normal projective variety whose Cox ring is defined by the Plucker ideal $I_{d,n}$ of the Grassmannian $\textrm{Gr}(d,n)$. We give a complete classification of all smooth Fano intrinsic Grassmannians of type $(2,n)$ with Picard number two and prove an explicit formula to compute the total number of such varieties for an arbitrary $n$. We study their geometry and show that they satisfy Fujita’s freeness conjecture.
Autologous Fat Grafting to the Breast: An Educational Review
Authors: Winkler Nicole S , Tran Alexander , Kwok Alvin C , Freer Phoebe E , Fajardo Laurie L 
Published: August 2021

AbstractAutologous fat grafting (AFG) is a technique that is increasingly utilized in breast cosmetic and reconstructive surgery. In this procedure, fat is aspirated by liposuction from one area of the body and injected into the breast. The procedure and process of AFG has evolved over the last few decades, leading to more widespread use, though there is no standard method. Autologous fat grafting is generally considered a safe procedure but may result in higher utilization of diagnostic imaging due to development of palpable lumps related to fat necrosis. Imaging findings depend on surgical technique but typically include bilateral, symmetric, retromammary oil cysts and scattered dystrophic and/or coarse calcifications when AFG is used for primary breast augmentation. More focal findings occur when AFG is used to improve specific areas of cosmetic deformity, scarring, or pain following breast cancer surgery. As with any cause of fat necrosis, imaging features tend to appear more benign over time, with development of rim calcifications associated with oil cysts and a shift in echogenicity of oil cyst contents on ultrasound towards anechoic in some cases. This article reviews the AFG procedure, uses, complications, and imaging findings.
Tomato SlPP2C5 Is Involved in the Regulation of Fruit Development and Ripening
Authors: Wang Juan , Xu Yandan , Zhang Wenbo , Zheng Yu , Yuan Bing , Li Qian , Leng Ping 
Published: August 2021

Abstract
Abscisic acid (ABA) regulates plant development mainly through its signaling, in which ABA binds to receptors to inhibit type 2C protein phosphatases (PP2Cs). The exact roles of PP2Cs in fruit development are still unclear. In this work, we verify that tomato SlPP2C5 works as a negative regulator in ABA signaling during fruit development. SlPP2C5 was inhibited by both monomeric and dimeric ABA receptors SlPYLs through ABA dose–dependent way, and it interacted physically with SlPYLs and SlSnRK2s. SlPP2C5 was highly expressed in fruits induced by exogenous ABA. Plants with overexpressed SlPP2C5 had lower sensitivity to ABA, which showed faster seed germination and primary root growth compared to Wild type (WT), while SlPP2C5-suppressed plants were more sensitive to ABA. SlPP2C5-over-expression (OE) delayed fruit ripening onset, while SlPP2C5-RNAi advanced fruit ripening. Alteration of SlPP2C5 expression impacts fruit quality parameters as well, including pericarp thickness, fruit shape index, seed number and weight and the soluble solid content. RNA-seq analysis revealed that there were significant expression differences of genes related to ethylene release and lycopene synthesis between WT and both SlPP2C5-OE and SlPP2C5-RNAi lines with an inversed variation. Taken together, our findings demonstrate that SlPP2C5 plays an important role in the regulation of fruit development, ripening and quality.
Genetic assessments of breast cancer risk that do not account for polygenic background are incomplete and lead to incorrect preventative strategies
Authors: Busby George B. , Craig Paul , Yousfi Nesrine , Hebbalkar Saurabh , Di Domenico Paolo , Bottà Giordano 
Published: August 2021

AbstractBreast cancer is the most common cancer among women and is a leading cause of cancer mortality worldwide. There is a significant genetic component to breast cancer risk which is the result of both rare pathogenic mutations and common genome-wide variation. However, the penetrance of pathogenic mutations varies widely and their frequency is low, both at a population level and amongst breast cancer cases. Polygenic risk scores, which aggregate the effect of hundreds to millions of common genome-wide variants offer a way to further understand the contribution of genetics to disease risk. Here we analyse genome-wide data from 221,479 women and 90,307 high coverage exomes to understand how rare and common variation affect lifetime breast cancer risk. We show that PRS strongly modulates the penetrance of mutations in 8 breast cancer susceptibility genes. For example, lifetime risk in BRCA1 carriers with low polygenic risk is almost one third that of carriers with high PRS (26% v 69% in the bottom and top PRS deciles, respectively). Adding family history of breast cancer provides additional stratification on the potential outcome of disease in carriers of rare mutations. PRS also identifies a significant fraction of the population at equivalent risk to carriers of moderate impact pathogenic variants and who are an order of magnitude more common at a population level. These results have important implications for breast cancer risk mitigation strategies, indicating that the genetic risk of breast cancer is determined by both monogenic mutation and polygenic background, and that assessments of genetic risk for breast cancer risk that do not consider the polygenic background are imprecise and unreliable.
First-in-human autologous oral mucosal epithelial sheet transplantation to prevent anastomotic re-stenosis in congenital esophageal atresia
Authors: Fujino Akihiro , Fuchimoto Yasushi , Baba Yoshiyuki , Isogawa Nobutaka , Iwata Takanori , Arai Katsuhiro , Abe Makoto , Kanai Nobuo , Takagi Ryo , Maeda Masanori , Umezawa Akihiro 
Published: August 2021

AbstractBackgroundCongenital esophageal atresia postoperative anastomotic stricture occurs in 30-50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture.MethodsEpithelial cell sheets were fabricated from a patient’s oral epithelial tissue, and their safety was confirmed by quality control tests. The epithelial cell sheets were transported under controlled conditions from the fabrication facility to the transplantation facility and successfully transplanted onto the lacerations caused by EBD using a newly developed transplantation device for pediatric patients. The safety of the transplantation was confirmed by follow-up examinations over 48 weeks.ResultsThe number of EBDs required after transplantation and the number of days between EDBs were recorded. Before transplantation, EBDs were performed approximately every two weeks, whereas after transplantation, the interval was extended to a maximum of four weeks. The patient was also aware of a reduction in dysphagia.ConclusionsThis study suggests that cell sheet transplantation might be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia. We chose this very severe case for the first clinical study in humans. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation.
Tau spreading is driven by neuronal connectivity in primary tauopathies - evidence from tau-PET and histopathology
Authors: Franzmeier Nicolai , Brendel Matthias , Beyer Leonie , Kovacs Gabor , Arzberger Thomas , Kurz Carolin , Respondek Gesine , Lukic Milica Jecmenica , Biel Davina , Rubinski Anna , Frontzkowski Lukas , Finze Anika , Palleis Carla , Joseph Emanuel , Weidinger Endy , Katzdobler Sabrina , Song Mengmeng , Biechele Gloria , Kern Maike , Scheifele Maximilian , Rauchmann Boris-Stephan , Perneczky Robert , Rullman Michael , Patt Marianne , Schildan Andreas , Barthel Henryk , Sabri Osama , Rumpf Jost J. , Schroeter Matthias L. , Classen Joseph , Villemagne Victor , Seybl John , Stephens Andrew W. , Lee Edward B. , Coughlin David G. , Giese Armin , Grossman Murray , McMillan Corey T. , Gelpi Ellen , Molina-Porcel Laura , Compta Yaroslau , van Swieten John C. , Laat Laura Donker , Troakes Claire , Al-Sarraj Safa , Robinson John L. , Xie Sharon X. , Irwin David J. , Roeber Sigrun , Herms Jochen , Simons Mikael , Bartenstein Peter , Lee Virginia M. , Trojanowski John Q. , Levin Johannes , Höglinger Günter U. , Ewers Michael ,   For the German Imaging Initiative for Tauopathies (GII4T) & the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2021

ABSTRACTTau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies (4RT), including cortico-basal degeneration and progressive supranuclear palsy (PSP). Tau is assumed to spread prion-like across connected neurons, but the mechanisms of tau propagation are largely elusive in 4RTs, characterized not only by neuronal but also by astroglial and oligodendroglial tau accumulation. Here, we assessed whether connectivity drives 4R-tau spreading patterns by combining resting-state fMRI connectomics with both 2nd generation 18F- PI-2620 tau-PET in 46 patients with clinically diagnosed 4RTs and post-mortem cell-type- specific regional tau assessments from two independent PSP samples (n=97/96). We found that inter-regional connectivity was associated with higher inter-regional correlation of both tau- PET and post-mortem tau levels in 4RTs. In regional cell-type specific post-mortem tau assessments, this association was stronger for neuronal than for astroglial or oligodendroglial tau, suggesting that connectivity is primarily associated with trans-neuronal tau spread. Using tau-PET we found that patient-level tau patterns can be predicted by the connectivity of subcortical tau epicenters. Together, the current study provides combined in vivo tau-PET and histopathological evidence for brain connectivity as a key mediator of trans-neuronal tau spreading in 4RTs.
A Longitudinal Normative Dataset and Protocol for Speech and Language Biomarker Research
Authors: Schwoebel James W. , Schwartz Joel , Warrenburg Lindsay A. , Brown Roland , Awasthi Ashi , New Austin , Butler Monroe , Moss Mark , Pissadaki Eleftheria K. 
Published: August 2021

AbstractAlthough speech and language biomarker (SLB) research studies have shown methodological and clinical promise, some common limitations of these studies include small sample sizes, limited longitudinal data, and a lack of a standardized survey protocol. Here, we introduce the Voiceome Protocol and the corresponding Voiceome Dataset as standards which can be utilized and adapted by other SLB researchers. The Voiceome Protocol includes 12 types of voice tasks, along with health and demographic questions that have been shown to affect speech. The longitudinal Voiceome Dataset consisted of the Voiceome Protocol survey taken on (up to) four occasions, each separated by roughly three weeks (22.80 +/- 20.91 days). Of 6,650 total participants, 1,382 completed at least two Voiceome surveys. The results of the Voiceome Dataset are largely consistent with results from standard clinical literature, suggesting that the Voiceome Study is a high-fidelity, normative dataset and scalable protocol that can be used to advance SLB research.
The SARS-CoV-2 Alpha variant is associated with increased clinical severity of COVID-19 in Scotland: a genomics-based retrospective cohort analysis
Authors: Pascall David J. , Vink Elen , Blacow Rachel , Bulteel Naomi , Campbell Alasdair , Campbell Robyn , Clifford Sarah , Davis Chris , da Silva Filipe Ana , Sakka Noha El , Fjodorova Ludmila , Forrest Ruth , Goldstein Emily , Gunson Rory , Haughney John , Holden Matthew T.G. , Honour Patrick , Hughes Joseph , James Edward , Lewis Tim , Lycett Samantha , MacLean Oscar , McHugh Martin , Mollett Guy , Onishi Yusuke , Parcell Ben , Ray Surajit , Robertson David L , Shabaan Sharif , Shepherd James G. , Smollett Katherine , Templeton Kate , Wastnedge Elizabeth , Wilkie Craig , Williams Thomas ,   The COVID-19 Genomics UK (COG-UK) consortium, Thomson Emma C. 
Published: August 2021

AbstractObjectivesThe SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this.MethodsIn this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1stNovember 2020 and 30thJanuary 2021 were sequenced. We matched sequence data to clinical outcomes as the variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death.ResultsOur cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus non-Alpha variant).ConclusionsThe Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.