bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic diversity and population structure of the Leonberger dog breed
Authors: Letko Anna , Minor Katie M. , Jagannathan Vidhya , Seefried Franz R. , Mickelson James R. , Oliehoek Pieter , Drögemüller Cord 
Published: October 2020

AbstractBackgroundLeonberger is a giant dog breed formed in the 1850s in Germany. Its post-World War II popularity has resulted in a current global population of ~ 30,000 dogs. The breed has predispositions to neurodegenerative disorders and cancer, which is likely due in large part to limited genetic diversity. However, to date there is no scientific literature on the overall demography and genomic architecture of this breed.ResultsWe assessed extensive pedigree records, SNP array genotype data, and whole-genome sequences (WGS) on 142,072, 1203 and 39 Leonberger dogs, respectively. Pedigree analyses identified 22 founder animals and revealed an apparent popular sire effect. The average pedigree-based inbreeding coefficient of 0.29 and average kinship of 0.31 show a dramatic loss of genetic diversity. The observed average life span decreased over time from 9.4 years in 1989 to 7.7 years in 2004. A global health survey confirmed a high prevalence of cancer and neurological disorders. Analysis of SNP-based runs of homozygosity (ROH) identified 125,653 ROH with an average length of 5.88 Mb, and confirmed an average inbreeding coefficient of 0.28. Genome-wide filtering of the WGS data revealed 28 non-protein-changing variants that were present in all Leonberger individuals and a list of 22 potentially pathogenic variants for neurological disorders of which 50% occurred only in Leonbergers and 50% occurred rarely in other breeds. Furthermore, one of the two mtDNA haplogroups detected was present in one dog only.ConclusionsThe increasing size of the Leonberger population has been accompanied by a considerable loss of genetic diversity after the bottleneck that occurred in the 1940s due to the intensive use of popular sires resulting in high levels of inbreeding. This might explain the high prevalence of certain disorders; however, genomic data provide no evidence for fixed coding variants that explain these predispositions. The list of candidate causative variants for polyneuropathy needs to be further evaluated. Preserving the current genetic diversity is possible by increasing the number of individuals for breeding while restricting the number of litters per sire/dam. In addition, outcrossing would help optimize long-term genetic diversity and contribute to the sustainability and health of the population.
Spatial and temporal modulation of enterotoxigenic E. coli H10407 pathogenesis and interplay with microbiota in human gut models
Authors: Roussel Charlène , De Paepe Kim , Galia Wessam , De Bodt Jana , Chalancon Sandrine , Leriche Françoise , Ballet Nathalie , Denis Sylvain , Alric Monique , Van de Wiele Tom , Blanquet-Diot Stéphanie 
Published: October 2020

AbstractBackgroundEnterotoxigenicEscherichia coli(ETEC) substantially contributes to the burden of diarrheal illnesses in developing countries. With the use of complementary in vitro models of the human digestive environment, TNO gastrointestinal model (TIM-1), and Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), we provided the first detailed report on the spatial-temporal modulation of ETEC H10407 survival, virulence, and its interplay with gut microbiota. These systems integrate the main physicochemical parameters of the human upper digestion (TIM-1) and simulate the ileumvsascending colon microbial communities and luminalvsmucosal microenvironments, captured from six fecal donors (M-SHIME).ResultsA loss of ETEC viability was noticed upon gastric digestion, while a growth renewal was found at the end of jejunal and ileal digestion. The remarkable ETEC mucosal attachment helped to maintain luminal concentrations above 6 log10 mL−1in the ileum and ascending colon up to 5 days post-infection. Seven ETEC virulence genes were monitored. Most of them were switched on in the stomach and switched off in the TIM-1 ileal effluents and in a late post-infectious stage in the M-SHIME ascending colon. No heat-labile enterotoxin production was measured in the stomach in contrast to the ileum and ascending colon. Using16SrRNA gene-based amplicon sequencing, ETEC infection modulated the microbial community structure of the ileum mucus and ascending colon lumen.ConclusionsThis study provides a better understanding of the interplay between ETEC and gastrointestinal cues and may serve to complete knowledge on ETEC pathogenesis and inspire novel prophylactic strategies for diarrheal diseases.
Platelet-to-lymphocyte ratio is correlated with a delay in feeding resumption following a transhiatal esophagectomy with cervical anastomosis
Authors: El Asmar Antoine , Ghabi Elie , Saber Toufic , Abou-Malhab Christina , Akl Bernard , El Rassi Ziad 
Published: October 2020

Abstract
Introduction
The lymphocytic population, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are prognostic tools predictive of adverse outcomes for several solid tumors and oncologic surgeries, one of which is esophageal adenocarcinoma. Furthermore, delayed resumption of oral feeding postoperatively is associated with significant morbidity. Given the controversies regarding post-op nutritional support in these patients, this study investigates the prognostic role of the lymphocytic percentage, the NLR, and the PLR in predicting prolonged length of hospital stay (LOHS) and ICU stay (LOICUS) as well as delayed oral feeding following transhiatal esophagectomy (THE) for adenocarcinoma of the esophagogastric junction (AEG).

Methods
Forty consecutive patients who underwent transhiatal esophagectomy performed by a single surgeon for Siewert type II and type III adenocarcinoma of the esophagogastric junction at a tertiary referral center were selected. Retrospective data collection was performed from the patients’ medical records, and statistical analysis was performed using Pearson correlation and Student’s t test and Chi-square testing.

Results
An increased LOHS was correlated with a lower preoperative lymphocyte percentage (p = 0.043), higher NLR (p = 0.010) and PLR (p = 0.015), and an increased number of packed red blood cell (PRBC) transfusions perioperatively (p = 0.030). An increased LOICUS was correlated with a lower preoperative lymphocyte percentage (p = 0.033), higher NLR (p = 0.018) and PLR (p = 0.044), an increased number of PRBC transfusions (p = 0.001), and patients’ comorbidities (p < 0.05). A delay in feeding resumption was correlated with a lower preoperative lymphocyte percentage (p = 0.022), higher NLR (p = 0.004) and PLR (p = 0.001), an increased PRBC transfusions (p = 0.001), and diabetes mellitus (p = 0.033). Multivariate analysis with automatic linear modeling showed that only the preoperative PLR was a powerful predictor for the delay of feeding resumption (p < 0.01).

Conclusion
The lymphocyte percentage, PLR, and NLR are found to be associated with prolonged hospitalization and ICU stay and delayed oral feeding following THE for Siewert types II and III AEG. We hope by this series, to have set, at least one preliminary cornerstone, in the creation of a prognostic model, capable of assessing the need for an intraoperative jejunostomy placement, in patients undergoing esophagectomy for distal esophageal carcinoma.
Human pegivirus (HPgV, GBV-C) RNA in volunteer blood donors from a public hemotherapy service in Northern Brazil
Authors: Silva Aniel de Sarom Negrão , Silva Clayton Pereira , Barata Rafael Ribeiro , da Silva Pedro Victor Reis , Monteiro Patrícia Danin Jordão , Lamarão Letícia , Burbano Rommel Mário Rodríguez , Nunes Márcio Roberto Teixeira , de Lima Patrícia Danielle Lima 
Published: October 2020

Abstract
Background
Human pegivirus (HPgV)—formerly known as GBV-C—is a member of the Flaviviridae family and belongs to the species Pegivirus C. It is a non-pathogenic virus and is transmitted among humans mainly through the exposure to contaminated blood and is often associated with human immunodeficiency virus (HIV) infection, among other viruses. This study aimed to determine the prevalence of HPgV viremia, its association with HIV and clinical epidemiological factors, as well as the full-length sequencing and genome characterization of HPgV recovered from blood donors of the HEMOPA Foundation in Belém-PA-Brazil.

Methods
Plasma samples were obtained from 459 donors, tested for the presence of HPgV RNA by the RT-qPCR. From these, a total of 26 RT-qPCR positive samples were submitted to the NGS sequencing approach in order to obtain the full genome. Genome characterization and phylogenetic analysis were conducted.

Results
The prevalence of HPgV was 12.42%. We observed the highest prevalences among donors aged between 18 and 30 years old (16.5%), with brown skin color (13.2%) and men (15.8%). The newly diagnosed HIV-1 prevalence was 26.67%. The HPgV genotype 2 (2a and 2b) was identified. No data on viral load value was found to corroborate the protective effect of HPgV on HIV evolution.

Conclusions
This study provided information regarding the HPgV infection among blood donors from HEMOPA Foundation. Furthermore, we genetically characterized the HPgV circulating strains and described by the first time nearly complete genomes of genotype 2 in Brazilian Amazon.
Diagnostic value of clusterin immunostaining in hepatocellular carcinoma
Authors: Li Yuan , Liu Fangfang , Zhou Wendi , Zhang Sharon , Chu Peiguo , Lin Fan , Wang Hanlin L. 
Published: October 2020

Abstract
Background
Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenge. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC.

Methods
Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs.

Results
Enhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26 and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC.

Conclusions
CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish well to moderately differentiated HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.
Leaf open time sinogram (LOTS): a novel approach for patient specific quality assurance of total marrow irradiation
Authors: Thiyagarajan Rajesh , Sharma Dayananda Shamurailatpam , Kaushik Suryakant , Sawant Mayur , Ganapathy K. , Nambi Raj N. Arunai , Chilukuri Srinivas , Sundar Sham C. , Patro Kartikeswar Ch. , Manikandan Arjunan , Noufal M. P. , Sivaraman Rangasamy , Easow Jose , Jalali Rakesh 
Published: October 2020

AbstractThere is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for Total Marrow (TMI) and Lymphoid (TMLI) Irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured Leaf Open Time Sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with (a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and (b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98% (D98%) and 2% (D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ± 1.80% of planned and IC measurement. The planned dose distribution agreed with reconstructed and ArcCheck measured dose with mean (SD) 3Dγ of 98.70% (1.57%) and 2Dγ of 99.48% (0.81%). The deviation in D98% and D2% were within 1.71% and 4.10% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agreed within ± 1.20%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from the five upper body TMI/TMLI plans showed mean ± SD 2Dγ of 97.82% ± 1.27%, the reconstruction method resulted poor mean (SD) 3Dγ of 92.00% (± 5.83%), 64.80% (± 28.28%), 69.20% (± 30.46%), 60.80% (± 19.37%) and 73.2% (± 20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were < 3.80% and 9.50%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% < 1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5 cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.
The prognostic value of the lymph node ratio for local advanced gastric cancer patients with intensity-modulated radiation therapy and concurrent chemotherapy after radical gastrectomy in China
Authors: Yang Yongqiang , Ma Yifu , Xiang Xiaoyong , Xing Pengfei , Wu Yongyou , Zhang Liyuan , Tian Ye 
Published: October 2020

Abstract
Background
Nearly 50% of new gastric cancer cases and gastric cancer-related deaths worldwide occur in China. No global consensus has been reached about the optimal management of locally advanced gastric cancer. Although the Guidelines for the Diagnosis and Treatment of Gastric Cancer from the National Health Commission of China, which has been updated three times since 2010, explicitly emphasize the necessity of adjuvant chemoradiation, few clinical institutions in China routinely adhere to the recommended radiotherapy guidelines. This study aimed to examine the efficacy, in terms of locoregional control and long-term survival, and the safety of adjuvant radiotherapy using intensity-modulated radiation therapy (IMRT) with concurrent and adjuvant fluoropyrimidine-based chemotherapy for gastric cancer.

Methods
This was a retrospective evaluation of 156 patients with high-risk gastric cancer who underwent adjuvant chemoradiotherapy between September 2008 and May 2019. The prescribed planning target volume median dose was 45 Gy in 1.8 Gy daily fractions, and all patients received concurrent and adjuvant fluoropyrimidine-based chemotherapy. Locoregional control, distant metastasis, and overall survival rates were estimated. Clinicopathological characteristics and patterns of failure were retrospectively reviewed to identify factors associated with survival and recurrence.

Results
The median follow-up duration was 56 months (range 3–130 months) for all patients. Of the patients, 11 (7.1%) were lost to follow-up, and 49 (31.4%) and 104 (66.7%) had stage II or III disease according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging criteria. The frequencies of acute grade 3 or 4 gastrointestinal and hematological toxicity were 9.6% and 10.9%, respectively. In total, 152 patients (97.4%) completed the entire chemoradiation regimen. No toxicity-related deaths occurred. Nineteen patients (12.2%) had locoregional recurrence, 26 (16.7%) had distant metastases, and 12 (7.7%) had peritoneal metastasis. The overall survival (OS) rates were 83.5%, 65.0%, and 59.5%, while the disease-free survival rates were 75.1%, 61.0%, and 55.6% at 1, 3, and 5 years, respectively. In the multivariate analysis, age, pathological T stage and lymph node ratio (LNR) were found to be independent predictors of OS.

Conclusion
Postoperative concomitant IMRT and chemotherapy were well tolerated, with acceptable toxicities and encouraging locoregional tumor control and long-term survival. The LNR can be used as an important prognostic indicator for OS. Adjuvant chemoradiotherapy should be considered for all patients with a high risk of locoregional recurrence, especially in China.
Long-term results of endoclamping in patients undergoing minimally invasive mitral valve surgery where external aortic clamping cannot be used – a propensity matched analysis
Authors: Cetinkaya Ayse , Ebraheem Emad , Bramlage Karin , Hein Stefan , Bramlage Peter , Choi Yeong-Hoon , Schönburg Markus , Richter Manfred 
Published: October 2020

Abstract
Background
Minimally invasive mitral valve surgery is standard of care in many centres and it is commonly associated with the need for cardiopulmonary bypass. Conventional external aortic clamping (exoclamping) is not always feasible, so endoaortic clamping (endoclamping) has evolved as a viable alternative. The aim of this study is to compare endoclamping (Intraclude™, Edwards Lifesciences) with exoclamping (Chitwood) during minimally invasive mitral valve procedures.

Methods
This single-centre study included 822 consecutive patients undergoing minimally invasive mitral valve procedures. The endoclamp was used in 64 patients and the exoclamp in 758. Propensity-score (PS) matching was performed resulting in 63 patients per group. Outcome measures included procedural variables, length of intensive care unit (ICU) and hospital stay, major adverse cardiac and cerebrovascular events (MACCE) and repeat surgery.

Results
The mean age was similar in the two group (62.2 [endoclamp] vs. 63.5 [exoclamp] years; p = 0.554), as were the cardiopulmonary bypass (145 vs. 156 min; p = 0.707) and the procedure time (203 vs. 211 min; p = 0.648). The X-clamp time was significantly shorter in the endoclamp group (88 vs. 99 min; p = 0.042). Length of ICU stay (25.0 vs. 23.0 h) and length of hospital stay (10.0 vs. 9.0 days) were slightly longer in the endoclamp group, but without statistical significance. There were nominal but no statistically significant differences between the groups in the rates of stroke, vascular complications, myocardial infarction or repeat mitral valve surgery. The conversion rate to open sternotomy approach was 2.4% without difference between groups. The estimated 7-year survival rate was similar for both groups (89.9% [endoclamp]; 84.0% [exoclamp]) with a hazard ratio of 1.291 (95% CI 0.453–3.680).

Conclusions
Endoaortic clamping is an appropriate and reasonably safe alternative to the conventional Chitwood exoclamp for patients in which the exoclamp cannot be used because the ascending aorta cannot be safely mobilised.
Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants
Authors: Tian Wen , Huang Yingzhao , Sun Liying , Guo Yang , Zhao Sen , Lin Mao , Dong Xiying , Zhong Wenyao , Yin Yuehan , Chen Zefu , Zhang Nan , Zhang Yuanqiang , Wang Lianlei , Lin Jiachen , Yan Zihui , Yang Xinzhuang , Zhao Junhui , Qiu Guixing , Zhang Jianguo , Wu Zhihong , Wu Nan ,   (Deciphering Disorders Involving Scoliosis, COmorbidities) study group
Published: October 2020

Abstract
Background
Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly.

Results
We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease.
Targeted next-generation sequencing was performed using patients’ blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype–phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005).

Conclusions
Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly.
Designing low-cost, accurate cervical screening strategies that take into account COVID-19: a role for self-sampled HPV typing
Authors: Ajenifuja Kayode Olusegun , Belinson Jerome , Goldstein Andrew , Desai Kanan T. , de Sanjose Silvia , Schiffman Mark 
Published: October 2020

Abstract
Background
We propose an economical cervical screening research and implementation strategy designed to take into account the typically slow natural history of cervical cancer and the severe but hopefully temporary impact of COVID-19. The commentary introduces the practical validation of some critical components of the strategy, described in three manuscripts detailing recent project results in Asia and Africa.
The main phases of a cervical screening program are 1) primary screening of women in the general population, 2) triage testing of the small minority of women that screen positive to determine need for treatment, and 3) treatment of triage-positive women thought to be at highest risk of precancer or even cancer. In each phase, attention must now be paid to safety in relation to SARS-CoV-2 transmission. The new imperatives of the COVID-19 pandemic support self-sampled HPV testing as the primary cervical screening method. Most women can be reassured for several years by a negative test performed on a self-sample collected at home, without need of clinic visit and speculum examination. The advent of relatively inexpensive, rapid and accurate HPV DNA testing makes it possible to return screening results from self-sampling very soon after specimen collection, minimizing loss to follow-up. Partial HPV typing provides important risk stratification useful for triage of HPV-positive women. A second “triage” test is often useful to guide management. In lower-resource settings, visual inspection with acetic acid (VIA) is still proposed but it is inaccurate and poorly reproducible, misclassifying the risk stratification gained by primary HPV testing. A deep-learning based approach to recognizing cervical precancer, adaptable to a smartphone camera, is being validated to improve VIA performance. The advent and approval of thermal ablation permits quick, affordable and safe, immediate treatment at the triage clinic of the majority of HPV-positive, triage-positive women.

Conclusions
Overall, only a small percentage of women in cervical screening programs need to attend the hospital clinic for a surgical procedure, particularly when screening is targeted to the optimal age range for detection of precancer rather than older ages with decreased visual screening performance and higher risks of hard-to-treat outcomes including invasive cancer.