bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Stability Evaluation of Two Internal Fixation Patterns of Extracapsular Condylar Fracture Based on One Novel Measuring Method
Authors: Liao Qian , Liang Zhuangzhuang , Zhang Peng , Xu Bing , Gui Haijun 
Published: July 2020

Purpose:
The most stable internal fixation pattern for extracapsular condylar fracture (ECF) has been controversial. In this study we aimed to evaluate the stability of 2 common internal fixation patterns using 1 or 2 miniplates separately. One novel measuring method based on the angle of miniplates’ localization was introduced.

Materials and Methods:
Twenty-seven patients with 30 sides of extracapsular condylar fracture were enrolled in this retrospective study. All cases were performed open reduction and internal fixation using 1 or 2 titanium plates with both the postoperative immediate CT (T1) and the over 6 months’ follow-up CT (T2). Mandibles and implants were segmented and reconstructed respectively using SIMPANT 14.04 software. For 1 miniplate group, the sagittal crossing angle (<1) between miniplate (P1) and posterior border of ipsilateral ramus was measured. For 2 miniplates group, the sagittal crossing angle (<2) between 2 miniplates (P2a, P2b) was measured. Both anteroposterior (∠AP) and mediolateral angle change (∠ML) of each miniplate between T1 and T2 was measured. The stability of 2 internal fixation patterns was measured and evaluated based on the angle change of miniplates. And also the stability of each internal fixation pattern could be investigated based on the relationship between the placement patterns of miniplates and the angle change.

Results:
Fifty-two miniplates were finally segmented and reconstructed successfully, including 8 of 1 miniplate group and 44 of 2 miniplate group. For 1 miniplate group, the average ∠AP and ∠ML were 6.10° and 8.54°, respectively. For 2 miniplate group, the average ∠AP and ∠ML of P2a were 3.02° and 2.56°, respectively, as well as 3.12° and 3.07° of P2b.

Conclusions:
The novel measuring method based on the angle of miniplates’ localization showed potential for the stability evaluation of internal fixation of condylar fracture. In summary, the internal fixation patterns using 2 miniplates shows better stability than that of 1 miniplate.
The Initial Experience on Thoracoscopic Sleeve Lobectomy: Continuous Suturing Technique of the Bronchial Anastomosis in 12 Cases
Authors: Ceylan Kenan C. , Acar Arkin , Örs Kaya Şeyda 
Published: July 2020

Background:
Sleeve resection is a widely performed type of operation in the surgical treatment of non–small cell lung cancer. Video-assisted thoracoscopic surgery (VATS) is now used even in central tumor surgeries of the lung with the increasing technology and experience. Sleeve resection cases performed through VATS in our clinic in recent years were presented with demographic, surgical, pathologic, and survey characteristics.

Materials and Methods:
Twelve patients who underwent sleeve resection with VATS in our clinic between November 2015 and August 2019 were included in the study. Operative, pathologic, and postoperative characteristics of the patients were examined.

Results:
A total of 12 patients, 3 female and 9 male individuals, were included in the study. The mean age of the patients was 61.7±12.9 years. According to the localization of the tumors, left upper lobectomy was performed in 4 patients and 8 patients underwent right upper lobectomy. During the sleeve anastomosis of the patients, 3/0 prolene sutures were used in 5 patients (36%) and 4/0 prolene sutures in 4 patients (36%), whereas 3/0 polydioxanone suture (PDS) was used in 3 patients (28%). The mean operation time was 288.2±77.1 (205 to 460) minutes and the mean anastomosis time was 70±18.5 (55 to 110) minutes. In the postoperative period, 1 patient who had acute myocardial infarction died on the fourth postoperative day. The mean postoperative drainage duration of the patients was 5.5±1.9 (3 to 10) days and the mean length of hospital stay was 6.4±1.9 (4 to 11) days. When the pathologic features were examined, the mean tumor diameter was found to be 2.5±1.2 (1 to 5.5) cm. The mean follow-up period was calculated as 26.1±15.6 months (2 to 47). Other than 1 patient who died, the follow-up of 11 patients still proceeds.

Conclusions:
VATS approach of sleeve resections, which is performed cautiously even by thoracotomy, is becoming more common. These operations, which could be performed in experienced centers, offer a postoperative period of less morbidity to the patients with the advantage of reduced postoperative pain, drainage time, and hospital stay.
Five-Year Weight Loss Outcomes in Laparoscopic Vertical Sleeve Gastrectomy (LVSG) Versus Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) Procedures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Osland Emma J. , Yunus Rossita M. , Khan Shahjahan , Memon Muhammed A. 
Published: July 2020

Background:
Laparoscopic vertical sleeve gastrectomy (LVSG) has overtaken the laparoscopic Roux-en-Y gastric bypass (LRYGB) as the most frequently performed bariatric surgical procedure. To date little has been reported on the long-term outcomes of the LVSG procedure comparative to the traditionally favoured LRYGB. We undertook a systematic review and meta-analysis to review the 5-year outcomes of comparing LVSG and LRYGB. We undertook a systematic review and meta-analysis to compare 5-year weight loss outcomes of randomized controlled trials comparing LVSG to LRYGB.

Materials and Methods:
Searches of electronic databases (PubMed, Embase, CINAHL, Cochrane) were undertaken for randomized controlled trials describing weight loss outcomes in adults at 5 years postoperatively. Where sufficient data was available to undertake meta-analysis, the Hartung-Knapp-Sidik-Jonkman estimation method for random effects model was utilized. The review was registered with PROSPERO and reported following in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Results:
Five studies met the inclusion criteria totaling 1028 patients (LVSG=520, LRYGB=508). Moderate but comparable levels of bias were observed within studies. Statistically significant body mass index loss ranged from −11.37 kg/m2 (range: −6.3 to −15.7 kg/m2) in the LVSG group and −12.6 kg/m2 (range: −9.5 to −15.4 kg/m2) for LRYGB at 5 years (P<0.001). Systematic review suggested that LRYGB produced a greater weight loss expressed as percent excess weight and percent excess body mass index loss than LVSG: this was not corroborated in the meta-analysis.

Conclusions:
Five year weight loss outcomes suggest both LRYGB and LVSG are effective in achieving significant weight loss at 5 years postoperatively, however, differences in reporting parameters limit the ability to reliably compare the outcomes using statistical methods. Furthermore, results may be impacted by large dropout rates and per protocol analysis of the 2 largest included studies. Further long-term studies are required to contradict or validate the results of this meta-analysis.
Rapid progression of aortic stenosis after initiation of teriparatide treatment: a case report
Authors: Solomon Arie , Birkenfeld Shlomo 
Published: July 2020

Introduction
Teriparatide, a recombinant formulation of endogenous PTH, is indicated for the treatment of osteoporosis in patients at high risk for fracture including postmenopausal women, men with primary or hypogonadal osteoporosis and patients with glucocorticoid-induced osteoporosis.

Case report
A 64-year-old Jewish osteoporotic woman initiated use of Teriparatide (FORTEOTM, 250 µg per 1 ml subcutaneously per day) in April 2018. Prior to therapy initiation, the patient has undergone eight echocardiograms with an aortic valve pressure gradient ranging between 29 and 39 mmHg, defined as mild aortic stenosis (AS), with no clear trend of progression. In two subsequent echo tests conducted 4 and 7 months after treatment initiation, there was a rapid progression of AS with gradient pressures of 55 and 58 mmHg, respectively.

Conclusion
Intermittent exposure to PTH analogues may be one of the causes of rapid progression of AS. Studies with sizeable populations are required to assess causal relationship between PTH analogues use and progression of AS.
A trade-off between resistance to infection and reproduction in primate evolution
Authors: Singh Sumnima , Thompson Jessica A. , Weis Sebastian , Sobral Daniel , Truglio Mauro , Yilmaz Bahtiyar , Rebelo Sofia , Cardoso Silvia , Gjini Erida , Nuñez Gabriel , Soares Miguel P. 
Published: July 2020

SUMMARYMost mammals express a functionalGGTA1gene encoding the N-acetyllactosaminide α-1,3-galactosyltransferase enzyme, which synthesizes Galα1-3Galβ1-4GlcNAc (αGal) and are thus tolerant to this self-expressed glycan epitope. Old World primates including humans, however, carryGGTA1loss-of-function mutations and lack αGal. Presumably, fixation of such mutations was propelled by natural selection, favoring the emergence of αGal-specific immunity, which conferred resistance to αGal-expressing pathogens. Here we show that loss ofGgta1function in mice enhances resistance to bacterial sepsis, irrespectively of αGal-specific immunity. Rather, the absence of αGal from IgG-associated glycans increases IgG effector function, via a mechanism associated with enhanced IgG-Fc gamma receptor (FcγR) binding. The ensuing survival advantage against sepsis comes alongside a cost of earlier onset of reproductive senescence. Mathematical modeling of this trade-off shows that under conditions of high exposure to virulent pathogens, selective pressure can fixGGTA1loss-of-function mutations, as likely occurred during the evolution of primates towards humans.
A diffusion-like process enables expansion of advantaged gene mutations in human colonic epithelium
Authors: Olpe Cora , Khamis Doran , Chukanova Maria , Kemp Richard , Marks Kate , Tatton Cerys , Lindskog Cecilia , Skoufou-Papoutsaki Nefeli , Nicholson Anna , Brunton-Sim Roxanne , Malhotra Shalini , ten Hoopen Rogier , Stanley Rachel , Winton Doug , Morrissey Edward 
Published: July 2020

AbstractColorectal cancer is thought to arise when the mutational burden of the clonal population of stem cells within a colonic crypt exceeds a certain threshold. Therefore, quantification of the fixation and subsequent expansion of somatic mutations in histologically normal epithelium is key to understanding colorectal cancer initiation. Here, using immunohistochemistry, loss of the histone demethylase KDM6A in normal human colonic epithelium is visualised. Interpretation of the age-related behaviour of KDM6A-negative clones revealed significant competitive advantage in intra-crypt dynamics. Further, subsequent clonal expansion into multi-crypt patches was quantified to reveal a significant 5-fold increase in crypt fission rate. To accomodate the local accumulation of new crypts, the role of crypt fusion was considered. However, no compensatory increase in fusion rate was found. Instead, evidence for crypt diffusion is presented and proposed as a means of accommodating clonal expansions. The threshold fission rate at which diffusion fails to accommodate new crypts, and which may promote polyp growth, is defined.
Macromolecular refinement of X-ray and cryo-electron microscopy structures with Phenix / OPLS3e for improved structure and ligand quality
Authors: van Zundert Gydo C.P. , Moriarty Nigel W. , Sobolev Oleg V. , Adams Paul D. , Borrelli Kenneth W. 
Published: July 2020

AbstractAccurate macromolecular structure refinement is of paramount importance in structure based drug discovery as it provides a gateway to using ligand binding free energy calculations and ligand docking techniques. When dealing with high-resolution data, a simple restraint model may be preferred when the data is able to guide atom parameters to an unambiguous location. However, at lower resolution, the additional information contained in a complex force field may aid in refinement by avoiding implausible structures permitted by the simpler restraints. With the advent of the resolution revolution in cryo-electron microscopy, low resolution refinement is common, and likewise increases the need for a reliable force field. Here we report on the incorporation of the OPLS3e force field with the VSGB2.1 solvation model in the widely used structure determination package Phenix. The implementation is versatile and can be used in both reciprocal and real space refinement, alleviating the need for manually creating accurate ligand restraint dictionaries in the form of CIF files. Our results show significantly improved structure quality at lower resolution for X-ray refinement with reduced ligand strain, while showing only a slight increase in Rfree. For real space refinement of cryo-EM based structures, we find comparable quality structures, goodness-of-fit and reduced ligand strain. In addition, we explicitly show how structure quality is related to the map-model cross correlation as a function of data weight, and how it can be an insightful tool for detecting both over- and underfitting, especially when coupled with ligand energies. Further, we have compiled a user-friendly start-to-end script for refining structures with Phenix/OPLS3e, which is available starting with the Schrödinger 2020-3 distribution.
“Single-nucleus RNA-seq2 reveals a functional crosstalk between liver zonation and ploidy”
Authors: Richter M. L. , Deligiannis I.K. , Danese A. , Lleshi E. , Coupland P. , Vallejos C.A. , Colome-Tatche M. , Martinez-Jimenez C.P. 
Published: July 2020

AbstractSingle-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity we have developed a single-nucleus RNA-seq2 method that allows deep characterization of nuclei isolated from frozen archived tissues. We have used this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobe. Our work has revealed a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.
STING Promotes Breast Cancer Cell Survival by an Inflammatory-Independent Nuclear Pathway Enhancing the DNA Damage Response
Authors: Cheradame Laura , Guerrera Ida Chiara , Gaston Julie , Schmitt Alain , Jung Vincent , Pouillard Marion , Radosevic-Robin Nina , Modesti Mauro , Judde Jean-Gabriel , Cairo Stefano , Goffin Vincent 
Published: July 2020

AbstractSTING (Stimulator of Interferon Genes) is a well-known endoplasmic reticulum-anchored adaptor of the innate immunity that triggers the expression of inflammatory cytokines in response to pathogen infection. In cancer cells, this pro-inflammatory pathway can be activated by genomic DNA damage potentiating antitumor immune responses. Here we report that STING promotes cancer cell survival and resistance to genotoxic treatment in a cell-autonomous manner. Mechanistically, we show that STING partly localizes at the inner nuclear membrane in various breast cancer cell lines and clinical tumor samples, and interacts with several proteins of the DNA damage response (DDR). STING overexpression enhances the amount of chromatin-bound DNA-dependent Protein Kinase (DNA-PK) complex, while STING silencing impairs DDR foci formation and DNA repair efficacy. Importantly, this function of STING is independent of its canonical pro-inflammatory pathway. This study highlights a previously unappreciated cell-autonomous tumor-promoting mechanism of STING that opposes its well-documented role in tumor immunosurveillance.Graphical abstract
Sparse parallel independent component analysis and its application to identify linked genomic and gray matter alterations underlying working memory impairment in attention-deficit/hyperactivity disorder
Authors: Duan Kuaikuai , Chen Jiayu , Calhoun Vince D. , Jiang Wenhao , Rootes-Murdy Kelly , Schoenmacker Gido , Silva Rogers F. , Franke Barbara , Buitelaar Jan K. , Hoogman Martine , Oosterlaan Jaap , Hoekstra Pieter J , Heslenfeld Dirk , Hartman Catharina A , Sprooten Emma , Arias-Vasquez Alejandro , Turner Jessica A. , Liu Jingyu 
Published: July 2020

AbstractMost psychiatric disorders are highly heritable and associated with altered brain structural and functional patterns. Data fusion analyses on brain imaging and genetics, one of which is parallel independent component analysis (pICA), enable the link of genomic factors to brain patterns. Due to the small to modest effect sizes of common genetic variants in psychiatric disorders, it is usually challenging to reliably separate disorder-related genetic factors from the rest of the genome with the typical size of clinical samples. To alleviate this problem, we propose sparse parallel independent component analysis (spICA) to leverage the sparsity of individual genomic sources. The sparsity is enforced by performing Hoyer projection on the estimated independent sources. Simulation results demonstrate that the proposed spICA yields improved detection of independent sources and imaging-genomic associations compared to pICA. We applied spICA to gray matter volume (GMV) and single nucleotide polymorphism (SNP) data of 341 unrelated adults, including 127 controls, 167 attention-deficit/hyperactivity disorder (ADHD) cases, and 47 unaffected siblings. We identified one SNP source significantly and positively associated with a GMV source in superior/middle frontal regions. This association was replicated with a smaller effect size in 317 adolescents from ADHD families, including 188 individuals with ADHD and 129 unaffected siblings. The association was found to be more significant in ADHD families than controls, and stronger in adults and older adolescents than younger ones. The identified GMV source in superior/middle frontal regions was not correlated with head motion parameters and its loadings (expression levels) were reduced in adolescent (but not adult) individuals with ADHD. This GMV source was associated with working memory deficits in both adult and adolescent individuals with ADHD. The identified SNP component highlights SNPs in genes encoding long non-coding RNAs and SNPs in genes MEF2C, CADM2, and CADPS2, which have known functions relevant for modulating neuronal substrates underlying high-level cognition in ADHD.
Impact of genetic susceptibility to multiple sclerosis on the T cell epigenome: proximal and distal effects
Authors: Roostaei Tina , Klein Hans-Ulrich , Felsky Daniel , Kivisäkk Pia , Connor Sarah M. , Kroshilina Alexandra , Yung Christina , Ma Yiyi , Kaskow Belinda J. , Shao Xiaorong , Rhead Brooke , Liu Jia , Patsopoulos Nikolaos , Barcellos Lisa F. , Weiner Howard L. , De Jager Philip L. 
Published: July 2020

ABSTRACTWe establish a genome-wide map of DNA methylation quantitative trait locus (mQTL) effects in CD4+T cells isolated from multiple sclerosis (MS) patients. Utilizing this map in a colocalization analysis, we identify 19 loci where the same haplotype drives both MS susceptibility and local (cis-) DNA methylation. We also identify two distant (trans-) mQTL effects of MS susceptibility loci: (1) a chromosome 16 MS locus affectsPRDM8methylation (a chromosome 4 region not previously associated with MS susceptibility), and (2) the aggregate effect of MS variants in the major histocompatibility complex (MHC, chromosome 6) influences DNA methylation nearPRKCAon chromosome 17. Both effects are replicated in independent samples. Overall, we present a new methylome-wide mQTL resource for a key cell type in inflammatory disease research, uncover functional consequences of MS susceptibility variants, including the convergence of MHC risk alleles onto a new gene target involved in predisposition to MS.
Endophilin Recruitment via GPCR Interactions Enables Membrane Curvature Generation in the Absence of Anionic Lipids
Authors: Mondal Samsuzzoha , Powers Imania , Narayan Karthik , Botterbusch Samuel , Baumgart Tobias 
Published: July 2020

AbstractThe Bin/Amphiphysin/Rvs (BAR) family protein endophilin plays key roles in membrane curvature generation during endocytosis of cellular receptors. The Src homology 3 (SH3) domain of endophilin interacts with the proline rich third intracellular loop (TIL) of various G-protein coupled receptors (GPCRs). While electrostatic interactions between BAR domain and anionic membrane lipids have been considered to be the major driving force in curvature generation, it is unclear how the direct interaction between TIL and SH3 affects this function and its coupling with receptor internalization. Here we show that TIL mediated interactions alone not only recruit endophilin to the membrane but also facilitate curvature sorting and curvature generating behavior of endophilin. To demonstrate this, we designed model membranes with covalently lipid-conjugated TIL and lipids without net negative charge so that endophilin was recruited exclusively via SH3/TIL interactions. We find curvature generation and curvature sorting under those conditions. Furthermore, we show that TIL interacts electrostatically with membranes in the presence of anionic lipids and that this interaction can interfere with binding of SH3. Overall, our study suggests that an interplay between TIL, charged membranes, BAR domain, and SH3 domain mediate membrane curvature generation to regulate receptor endocytosis following receptor stimulation.
Multi-Drug-Resistance in Drug-Naive and Drug-Exposed Ovarian Cancer Cell Lines Responds Differently to Cell Culture Dimensionality
Authors: Koshkin Vasilij , de Oliveira Mariana Bleker , Peng Chun , Ailles Laurie E. , Liu Geoffrey , Covens Allan , Krylov Sergey N. 
Published: July 2020

AbstractDoes cell clustering influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naïve (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust “cell number vs. MDR efflux rate constant (kMDR)” histograms. Both drug-naïve and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naïve cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells.
PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response
Authors: Kim Chiho , Wang Xu-dong , Yu Yonghao 
Published: July 2020

AbstractIt is being increasingly appreciated that the immunomodulatory functions of PARP inhibitors (PARPi) underlie their clinical activities in variousBRCA-mutated tumors. PARPi possess both PARP1 inhibition and PARP1 trapping activities. The relative contribution of these two mechanisms toward PARPi-induced innate immune signaling, however, is poorly understood. We find that the presence of the PARP1 protein with uncompromised DNA-binding activities is required for PARPi-induced innate immune response. The activation of cGAS-STING signaling induced by various PARPi closely depends on their PARP1 trapping activities. Finally, we show that a small molecule PARP1 degrader blocks the enzymatic activity of PARP1 without eliciting PARP1 trapping or cGAS-STING activation. Our findings thus identify PARP1 trapping as a major contributor of the immunomodulatory functions of PARPi. Although PARPi-induced innate immunity is highly desirable in human malignancies, the ability of “non-trapping” PARP1 degraders to avoid the activation of innate immune response could be useful in non-oncological diseases.