bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of common variants in GDF5 gene on the susceptibility to chronic postsurgical pain
Authors: Yan Shaoyao , Nie Huiyong , Bu Gang , Yuan Weili , Wang Suoliang 
Published: July 2021

Abstract
Background
The growth differentiation factor 5 (GDF5) gene regulates the growth of neuronal axons and dendrites and plays a role in the inflammatory response and tissue damage. The gene may also be associated with chronic postsurgical pain. This study aimed to reveal the relationship between SNPs in the GDF5 gene and orthopedic chronic postsurgical pain in Han Chinese population based on a case-control study.

Methods
We genotyped 8 SNPs within GDF5 gene in 1048 surgical patients with chronic postsurgical pain as the case group and 2062 surgical patients who were pain free as the control group. SNP and haplotypic analyses were performed, and stratified analyses were conducted to determine the correlations between significant SNPs and clinical characteristics.

Results
Only rs143384 in the 5′UTR of GDF5 was identified as significantly associated with increased susceptibility to chronic postsurgical pain, and the risk of A allele carriers was increased approximately 1.35-fold compared with that of G allele carriers. Haplotypes AGG and GGG in the LD block rs143384-rs224335-rs739329 also showed similar association patterns. Furthermore, we found that rs143384 was significantly correlated with chronic postsurgical pain in the subgroup aged ≤ 61 years, subgroup with a BMI ≤ 26, subgroup with no-smoking or no pain history, and subgroup with a drinking history.

Conclusion
Our study provided supportive evidence that genetic variations in the GDF5 gene are potential genetic factors that can increase the risk of chronic postsurgical pain in the Han Chinese population, but further research is necessary to elucidate the underlying mechanism.
Stakeholders’ perspectives on integrating the management of depression into routine HIV care in Uganda: qualitative findings from a feasibility study
Authors: Rutakumwa Rwamahe , Ssebunnya Joshua , Mugisha James , Mpango Richard Steven , Tusiime Christine , Kyohangirwe Leticia , Taasi Geoffrey , Sentongo Hafsa , Kaleebu Pontiano , Patel Vikram , Kinyanda Eugene 
Published: July 2021

Abstract
Background
HIV/AIDS continues to be a major global public health problem with Eastern and Southern Africa being the regions most affected. With increased access to effective antiretroviral therapy, HIV has become a chronic and manageable disease, bringing to the fore issues of quality of life including mental wellbeing. Despite this, the majority of HIV care providers in sub-Saharan Africa, including Uganda’s Ministry of Health, do not routinely provide mental health care including depression management. The purpose of this paper is to explore stakeholders’ perspectives on the feasibility and acceptability of integrating depression management into routine adult HIV care. The paper addresses a specific objective of the formative phase of the HIV + D study aimed at developing and evaluating a model for integrating depression management into routine HIV care in Uganda.

Methods
This was a qualitative study. Data were collected through in-depth interviews with 11 patients at enrollment and follow-up in the pilot phase, and exit interviews with 11 adherent patients (those who completed their psychotherapy sessions) and six non-adherent patients (those missing at least two sessions) at the end of the pilot phase. Key informant interviews were held with four clinicians, five supervisors and one mental health specialist, as were three focus group discussions with lay health workers. These were purposively sampled at four public health facilities in Mpigi District. Data were analysed thematically.

Results
Patients highlighted the benefits of treating depression in the context of HIV care, including improved adherence to antiretroviral therapy, overcoming sleeplessness and suicidal ideation, and regaining a sense of self-efficacy. Although clinicians and other stakeholders reported benefits of treating depression, they cited challenges in managing depression with HIV care, which were organisational (increased workload) and patient related (extended waiting time and perceptions of preferential treatment). Stakeholders generally shared perspectives on how best to integrate, including recommendations for organisational level interventions–training, harmonisation in scheduling appointments and structural changes–and patient level interventions to enhance knowledge about depression.

Conclusions
Integrating depression management into routine HIV care in Uganda is acceptable among key stakeholders, but the technical and operational feasibility of integration would require changes both at the organisational and patient levels.
Inhibiting the redox function of APE1 suppresses cervical cancer metastasis via disengagement of ZEB1 from E-cadherin in EMT
Authors: Li Qing , Zhou Zhi-Wei , Duan Wei , Qian Cheng-Yuan , Wang Shu-Nan , Deng Meng-Sheng , Zi Dan , Wang Jian-Min , Mao Cheng-Yi , Song Guanbin , Wang Dong , Westover Kenneth D. , Xu Cheng-Xiong 
Published: July 2021

Abstract
Background
Metastasis is a major challenge in cervical cancer treatment. Previous studies have shown that the dual functional protein apurinic/apyrimidinic endonuclease 1 (APE1) promotes tumor metastasis and is overexpressed in cervical cancer. However, the biological role and mechanism of APE1 in cervical cancer metastasis have rarely been studied.

Methods
We used gene set enrichment analysis (GSEA) to determine the APE1-related signaling pathways in cervical cancer. To investigate the role and mechanism of APE1 in cervical cancer metastasis and invasion, immunohistochemistry, immunofluorescence, western blotting, secondary structure prediction, coimmunoprecipitation, luciferase reporter, and electrophoretic mobility shift assays were performed. The inhibitory effects of the APE1 redox function inhibitor APX3330 on cervical cancer metastasis were evaluated using animal models.

Results
Clinical data showed that high expression of APE1 was associated with lymph node metastasis in cervical cancer patients. GSEA results showed that APE1 was associated with epithelial to mesenchymal transition (EMT) in cervical cancer. Ectopic expression of APE1 promoted EMT and invasion of cervical cancer cells, whereas inhibition of APE1 suppressed EMT and invasion of cervical cancer cells in a redox function-dependent manner. Notably, APE1 redox function inhibitor APX3330 treatment dramatically suppressed cervical cancer cell lymph node and distant metastasis in vivo. Furthermore, we found that APE1 enhanced the interaction between ZEB1 and the E-cadherin promoter by binding to ZEB1, thereby suppressing the expression of E-cadherin, a negative regulator of EMT.

Conclusion
Our findings help to elucidate the role played by APE1 in cervical cancer metastasis and targeting APE1 redox function may be a novel strategy for inhibiting cervical cancer metastasis.
Massive hemobilia caused by rupture of gastroduodenal artery pseudoaneurysm, a delayed complication of laparoscopic cholecystectomy: a case report
Authors: Kurniawan Kurniawan , Wibawa I Dewa Nyoman , Somayana Gde , Mariadi I Ketut , Mulyawan I Made 
Published: July 2021

Abstract
Background
Hemobilia is a rare cause of upper gastrointestinal bleeding that originates from the biliary tract. It is infrequently considered in diagnosis, especially in the absence of abdominal trauma or history of hepatopancreatobiliary procedure, such as cholecystectomy, which can cause arterial pseudoaneurysm. Prompt diagnosis is crucial because its management strategy is distinct from other types of upper gastrointestinal bleeding. Here, we present a case of massive hemobilia caused by the rupture of a gastroduodenal artery pseudoaneurysm in a patient with a history of laparoscopic cholecystectomy 3 years prior to presentation.

Case presentation
A 44-year-old Indonesian female presented to the emergency department with complaint of hematemesis and melena accompanied by abdominal pain and icterus. History of an abdominal trauma was denied. However, she reported having undergone a laparoscopic cholecystectomy 3 years prior to presentation. On physical examination, we found anemic conjunctiva and icteric sclera. Nonvariceal bleeding was suspected, but esophagogastroduodenoscopy showed a blood clot at the ampulla of Vater. Angiography showed contrast extravasation from a gastroduodenal artery pseudoaneurysm. The patient underwent pseudoaneurysm ligation and excision surgery to stop the bleeding. After surgery, the patient’s vital signs were stable, and there was no sign of rebleeding.

Conclusion
Gastroduodenal artery pseudoaneurysm is a rare complication of laparoscopic cholecystectomy. The prolonged time interval, as compared with other postcholecystectomy hemobilia cases, resulted in hemobilia not being considered as an etiology of the gastrointestinal bleeding at presentation. Hemobilia should be considered as a possible etiology of gastrointestinal bleeding in patients with history of cholecystectomy, regardless of the time interval between the invasive procedure and onset of bleeding.
Bin2vec: learning representations of binary executable programs for security tasks
Authors: Arakelyan Shushan , Arasteh Sima , Hauser Christophe , Kline Erik , Galstyan Aram 
Published: July 2021

AbstractTackling binary program analysis problems has traditionally implied manually defining rules and heuristics, a tedious and time consuming task for human analysts. In order to improve automation and scalability, we propose an alternative direction based on distributed representations of binary programs with applicability to a number of downstream tasks. We introduce Bin2vec, a new approach leveraging Graph Convolutional Networks (GCN) along with computational program graphs in order to learn a high dimensional representation of binary executable programs. We demonstrate the versatility of this approach by using our representations to solve two semantically different binary analysis tasks – functional algorithm classification and vulnerability discovery. We compare the proposed approach to our own strong baseline as well as published results, and demonstrate improvement over state-of-the-art methods for both tasks. We evaluated Bin2vec on 49191 binaries for the functional algorithm classification task, and on 30 different CWE-IDs including at least 100 CVE entries each for the vulnerability discovery task. We set a new state-of-the-art result by reducing the classification error by 40% compared to the source-code based inst2vec approach, while working on binary code. For almost every vulnerability class in our dataset, our prediction accuracy is over 80% (and over 90% in multiple classes).
Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial
Authors: D'Amico Anthony V. , Xie Wanling , McMahon Elizabeth , Loffredo Marian , Medeiros Shana , Joseph David , Denham Jim , Kumar Parvesh , Bubley Glenn , Sullivan Molly , Hellwig Richard , Carlos Vera Juan , Freter Rolf , Jeffrey Baker W. , Wong Jeffrey Y. , Renshaw Andrew A. , Kantoff Philip W. 
Published: July 2021

PURPOSEAlthough docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.METHODSBetween September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2once every 3 weeks for three cycles before RT and 20 mg/m2once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors.RESULTSAfter a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL.CONCLUSIONAdding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.
EHF is essential for epidermal and colonic epithelial homeostasis, and suppresses Apc-initiated colonic tumorigenesis
Authors: Reehorst Camilla M. , Nightingale Rebecca , Luk Ian Y. , Jenkins Laura , Koentgen Frank , Williams David S. , Darido Charbel , Tan Fiona , Anderton Holly , Chopin Michael , Schoffer Kael , Eissmann Moritz F. , Buchert Michael , Mouradov Dmitri , Sieber Oliver M. , Ernst Matthias , Dhillon Amardeep S. , Mariadason John M. 
Published: July 2021

ABSTRACT
Ets homologous factor (EHF) is a member of the epithelial-specific Ets (ESE) family of transcription factors. To investigate its role in development and epithelial homeostasis, we generated a series of novel mouse strains in which the Ets DNA-binding domain of Ehf was deleted in all tissues (Ehf−/−) or specifically in the gut epithelium. Ehf−/− mice were born at the expected Mendelian ratio, but showed reduced body weight gain, and developed a series of pathologies requiring most Ehf−/− mice to reach an ethical endpoint before reaching 1 year of age. These included papillomas in the facial skin, abscesses in the preputial glands (males) or vulvae (females), and corneal ulcers. Ehf−/−mice also displayed increased susceptibility to experimentally induced colitis, which was confirmed in intestinal-specific Ehf knockout mice. Gut-specific Ehf deletion also impaired goblet cell differentiation, induced extensive transcriptional reprogramming in the colonic epithelium and enhanced Apc-initiated adenoma development. The Ets DNA-binding domain of EHF is therefore essential for postnatal homeostasis of the epidermis and colonic epithelium, and its loss promotes colonic tumour development.
Case Report: Pseudomonas can take a toll on a patient
Authors: Buchbinder David K. , Singh Jasjit , Dao Tuan , Sassoon Aaron , Arrieta Antonio 
Published: July 2021

Pseudomonas aeruginosa (P. aeruginosa) is an aerobic Gram-negative bacterium that is implicated in the development of severe systemic infections among pediatric patients. It is identified in hospitalized chronically ill pediatric patients in association with genitourinary, respiratory tract, and skin or soft tissue infections as well as severe and life-threating infection including sepsis. A variety of immunologic mechanisms play a vital role in the host defense mechanisms against invasive infections with P. aeruginosa. Rarely, specific inborn errors of immune function are implicated in deficiencies that predispose to invasive infections with P. aeruginosa. Innate immune function including germ-line encoded pattern recognition receptors such as toll-like receptors (TLRs) and their downstream signaling is vital in the host defense against P. aeruginosa through the generation of antimicrobial peptides, cytokines/chemokines, and shaping of adaptive immune responses. Herein, we describe a previously healthy two-year-old female with an invasive skin, soft tissue, and central nervous system infection secondary to P. aeruginosa. The invasive nature of this infection prompted a careful evaluation for an inborn error of immunity. Decreased cytokine response to agonists of TLRs was documented. Targeted sequencing of interleukin-1 receptor-associated kinase (IRAK)-4 documented a homozygous deletion of exons 8-13 consistent with IRAK-4 deficiency. This report provides a vital educative message in the existing scientific literature by underscoring the importance of considering inborn errors of immunity in all patients with severe P. aeruginosa infections. Functional assessments of immune function often in combination with sequencing can accurately assign a diagnosis in a timely fashion allowing for definitive treatment and the use of necessary supportive care.
DIE ATTRIBUTE DER REVALER KAUFLEUTE – EIN BLICK AUF DAS RETABEL DES MARIENALTARES DER BRUDERSCHAFT DER SCHWARZENHÄUPTER
Authors: Palginõmm Kerttu 
Published: July 2021

The article focuses on the Tallinn (Reval) altarpiece of St. Mary's altar ofthe Brotherhood of the Blackheads, attributed to the Bruges Master ofthe Legend of St. Lucy, which arrived in the late medieval city in 1493.The altarpiece is noteworthy for its very dense network of luxuriousdetails like silk, velvet and gold cloth from Italy, ceramics from Spain,tapestries from Netherlands and an oriental carpet from Anatolia. Early
Netherlandish painting is notable for the very detailed, texture andlight-sensitive rendering of everyday and luxury objects, from whichthe works of Jan van Eyck are the best examples.
Transitional vertebrae and numerical variants of the spine
Authors: Sugiura Kosuke , Morimoto Masatoshi , Higashino Kosaku , Takeuchi Makoto , Manabe Akihiro , Takao Shoichiro , Maeda Toru , Sairyo Koichi 
Published: July 2021

Aims Although lumbosacral transitional vertebrae (LSTV) are well-documented, few large-scale studies have investigated thoracolumbar transitional vertebrae (TLTV) and spinal numerical variants. This study sought to establish the prevalence of numerical variants and to evaluate their relationship with clinical problems. Methods A total of 1,179 patients who had undergone thoracic, abdominal, and pelvic CT scanning were divided into groups according to the number of thoracic and lumbar vertebrae, and the presence or absence of TLTV or LSTV. The prevalence of spinal anomalies was noted. The relationship of spinal anomalies to clinical symptoms (low back pain, Japanese Orthopaedic Association score, Roland-Morris Disability Questionnaire) and degenerative spondylolisthesis (DS) was also investigated. Results Normal vertebral morphology (12 thoracic and five lumbar vertebrae without TLTV and LSTV) was present in 531 male (76.7%) and 369 female patients (75.8%). Thoracolumbar transitional vertebrae were present in 15.8% of males and 16.0% of females. LSTV were present in 7.1% of males and 9.0% of females. The prevalence of the anomaly of 16 presacral mobile vertebrae (total number of thoracolumbar vertebrae and TLTV) without LSTV was 1.0% in males and 4.1% in females, and that of the anomaly of 18 vertebrae without LSTV was 5.3% in males and 1.2% in females. The prevalence of DS was significantly higher in females with a total of 16 vertebrae than in those with normal morphology. There was no significant correlation between a spinal anomaly and clinical symptoms. Conclusion Overall, 24% of subjects had anomalies in the thoracolumbar region: the type of anomaly differed between males and females, which could have significant implications for spinal surgery. A decreased number of vertebrae was associated with DS: numerical variants may potentially be a clinical problem. Cite this article: Bone Joint J 2021;103-B(7):1301–1308.
Is there a problem with modular dual mobility acetabular components in revision total hip arthroplasty at mid-term follow-up?
Authors: Hernandez Nicholas M. , Hinton Zoe W. , Wu Christine J. , Lachiewicz Paul F. , Ryan Sean P. , Wellman Samuel S. 
Published: July 2021

Aims Modular dual mobility (MDM) acetabular components are often used with the aim of reducing the risk of dislocation in revision total hip arthroplasty (THA). There is, however, little information in the literature about its use in this context. The aim of this study, therefore, was to evaluate the outcomes in a cohort of patients in whom MDM components were used at revision THA, with a mean follow-up of more than five years. Methods Using the database of a single academic centre, 126 revision THAs in 117 patients using a single design of an MDM acetabular component were retrospectively reviewed. A total of 94 revision THAs in 88 patients with a mean follow-up of 5.5 years were included in the study. Survivorship was analyzed with the endpoints of dislocation, reoperation for dislocation, acetabular revision for aseptic loosening, and acetabular revision for any reason. The secondary endpoints were surgical complications and the radiological outcome. Results The overall rate of dislocation was 11%, with a six-year survival of 91%. Reoperation for dislocation was performed in seven patients (7%), with a six-year survival of 94%. The dislocations were early (at a mean of 33 days) in six patients, and late (at a mean of 4.3 years) in four patients. There were three intraprosthetic dissociations. An outer head diameter of ≥ 48 mm was associated with a lower risk of dislocation (p = 0.013). Lumbrosacral fusion was associated with increased dislocation (p = 0.004). Four revision THAs (4%) were further revised for aseptic acetabular loosening, and severe bone loss (Paprosky III) at the time of the initial revision was significantly associated with further revision for aseptic acetabular loosening (p = 0.008). Fourteen acetabular components (15%) were re-revised for infection, and a pre-revision diagnosis of reimplantation after periprosthetic joint infection (PJI) was associated with subsequent PJI (p < 0.001). Two THAs had visible metallic changes on the backside of the cobalt chromium liner. Conclusion When using this MDM component in revision THA, at a mean follow-up of 5.5 years, there was a higher rate of dislocation (11%) than previously reported. The size of the outer bearing was related to the risk of dislocation. There was a low rate of aseptic acetabular loosening. Longer follow-up of this MDM component and evaluation of other designs are warranted. Cite this article: Bone Joint J 2021;103-B(7 Supple B):66–72.