bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic Roles of RAD51AP1 in Tumor Tissues Related to Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma
Authors: Zhuang Liping , Zhang Yuan , Meng Zhiqiang , Yang Zongguo 
Published: December 2020

Objective: This study aimed to investigate the associations between RAD51AP1 and the outcomes of hepatocellular carcinoma (HCC). Methods: RAD51AP1 expression levels were compared in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The Liver Hepatocellular Carcinoma (TCGA, Provisional) and GSE36376 datasets were used for survival analysis. RAD51AP1 associations with clinicopathological features were determined with the GSE36376 dataset. Results: RAD51AP1 mRNA expression was significantly upregulated in advanced liver fibrosis samples (S3-4 vs. S0-2 and G3-4 vs. G0-2) from hepatitis B virus (HBV)-related liver fibrosis patients and in tumor tissues and peripheral blood mononuclear cells (PBMCs) from HCC patients (all P < 0.05). HCC patients with high RAD51AP1 expression had significantly worse overall survival (OS) and disease-free survival (DFS) than those with low RAD51AP1 expression ( P = 0.0034 and P = 0.0012, respectively) in the TCGA dataset, and these findings were validated with the GSE36376 dataset ( P = 0.0074 and P = 0.0003, respectively). A Cox regression model indicated that RAD51AP1 was a risk factor for OS and DFS in HCC patients in GSE36376 (HR = 1.54, 95% CI = 1.02-2.32, P = 0.04 and HR = 1.71, 95% CI = 1.22-2.39, P = 0.002, respectively). Moreover, RAD51AP1 mRNA expression increased gradually with increasing tumor stage, including stratification by American Joint Committee on Cancer (AJCC) stages, Barcelona Clinic Liver Cancer (BCLC) stages and Edmondson grades. In addition, RAD51AP1 was overexpressed in HCC patients with intrahepatic metastasis, major portal vein invasion, vascular invasion and/or an alpha-fetoprotein (AFP) level > 300 ng/ml. Conclusions: Contributing to an advanced tumor stage, intrahepatic metastasis, vascular invasion and AFP level elevation, RAD51AP1 upregulation was significantly associated with OS and DFS in HCC patients.
Long-term effect of neutering on plasma luteinising hormone concentration in cats
Authors: Aguiar Joana , Crossley Victoria J , Davison Lucy J , Fowkes Robert C , Syme Harriet M 
Published: December 2020

Objectives The objectives of this study were to validate a commercially available luteinising hormone (LH) cat ELISA, to determine whether the increases in plasma LH concentration that occur after neutering are maintained throughout cats’ lives and if other factors such as calendar seasons in both intact and neutered cats, and neutering age in neutered cats, influence plasma LH concentrations. Methods Stored plasma samples from client-owned cats were used for the measurement of LH concentrations. Clinical data, including age, sex, age at neutering and medical history, were reviewed. Two populations were included in this study: (1) a senior and geriatric cat population (⩾9 years old), including 18 intact and 18 neutered cats matched for age, sex and month of sample collection; and (2) an adult cat population (2–8 years old), including 45 neutered cats. LH concentrations were measured using a commercially available feline ELISA. Results Senior and geriatric neutered cats had higher plasma LH concentrations than age-matched intact cats ( P <0.001). Calendar season did not influence plasma LH concentrations in the adult ( P = 0.727) or senior/geriatric ( P = 0.745) cats included in this study. No influence of age at neutering was observed on plasma LH concentrations ( P = 0.296). Conclusions and relevance Neutering causes a significant long-term increase in LH concentrations in cats and further studies are required to determine the consequences on feline health.
Prevalence, prognosis, and treatment of atherosclerotic intracranial stenosis in Caucasians
Authors: Hurford Robert , Rothwell Peter M 
Published: December 2020

Background Intracranial atherosclerotic stenosis is a highly prevalent cause of stroke worldwide with important ethnic disparities. Widely considered to be a common cause of stroke in Asian and Afro-Caribbean populations, relatively less is known about the burden and significance of intracranial atherosclerotic stenosis in Caucasians. Aims We aim to highlight recent insights and advances into the prevalence, prognosis, and treatment of symptomatic and asymptomatic atherosclerotic intracranial atherosclerotic stenosis in Caucasian patients. Summary of review We identified 48 articles studying intracranial atherosclerotic stenosis in Caucasian patients with ischemic stroke or transient ischemic attack. Most studies were on hospital-based cohorts of consecutive patients and half were graded as “fair” quality. There was significant variation between studies in the definition of intracranial atherosclerotic stenosis and in the imaging modalities used to detect intracranial atherosclerotic stenosis. Overall, 12.1% of Caucasian patients were found to have any intracranial atherosclerotic stenosis, 6.4% symptomatic intracranial atherosclerotic stenosis and 11.1% asymptomatic intracranial atherosclerotic stenosis, with higher rates at older ages. In studies reporting prognosis, there were 61 and 10 same-territory ischemic strokes in 1000 person-years in patients with symptomatic and asymptomatic intracranial atherosclerotic stenosis, respectively. Percutaneous stenting and angioplasty have not proven superior to intensive medical management in patients with symptomatic intracranial atherosclerotic stenosis. Conclusions Intracranial atherosclerotic stenosis has previously been neglected as a cause of stroke in Caucasians but is highly prevalent at older ages and frequently discovered with the growing use of noninvasive angiography. Intensive medical therapy is the treatment of choice, but there is a need to develop novel treatments or therapeutic approaches to lower the risk of stroke in higher risk patients.
From Patient to Procedure: The Process of Creating a Custom 3D-Printed Medical Device for Foot and Ankle Pathology
Authors: Kadakia Rishin J. , Wixted Colleen M. , Kelly Cambre N. , Hanselman Andrew E. , Adams Samuel B. 
Published: December 2020

Three-dimensional (3D) printing technology has advanced greatly over the past decade and is being used extensively throughout the field of medicine. Several orthopaedic surgery specialties have demonstrated that 3D printing technology can improve patient care and physician education. Foot and ankle pathology can be complex as the 3D anatomy can be challenging to appreciate. Deformity can occur in several planes simultaneously and bone defects either from previous surgery or trauma can further complicate surgical correction. Three-dimensional printing technology provides an avenue to tackle the challenges associated with complex foot and ankle pathology. A basic understanding of how these implants are designed and made is important for surgeons as this technology is becoming more widespread and the clinical applications continue to grow within foot and ankle surgery. Levels of Evidence: Level V
Self-care practice and associated factors among hypertensive patients in public health facilities in Harar Town, Eastern Ethiopia: A cross-sectional study
Authors: Hussen Feysal Mohammed , Adem Hassen Abdi , Roba Hirbo Shore , Mengistie Bezatu , Assefa Nega 
Published: December 2020

Background: Self-care practice is the activity that a hypertensive patient undertakes intending to improve their health. Poor self-care practice leads to uncontrolled hypertension. Therefore, strategies designed to prevent and control hypertension-related death, disability, and morbidity should consider the level of the patient’s self-care practice and risk factors. This study assessed self-care practice and associated factors among hypertensive patients in public health facilities of Harar Town in eastern Ethiopia. Method: An institution-based cross-sectional study was conducted among 398 randomly selected hypertensive patients from 25 March 2019 to 16 April 2019. Pretested structured questionnaires adapted from validated tools were used to collect data from participants using electronic Open Data Kit software through face-to-face exit interview. Data were analyzed by SPSS version 24. Bivariable and multivariable logistic regression analyses were conducted to identify factors associated with self-care practice. Adjusted odds ratio with 95% confidence interval was used to report association and the significance was declared at p-value < 0.05. Results: Level of good self-care practice was 29.9% (95% confidence interval: 25.3% and 34.7%). Age ⩾ 60 years (adjusted odds ratio = 3.4, 95% confidence interval: 1.2 and 9.3), formal education (adjusted odds ratio = 2.3, 95% confidence interval: 1.3 and 4.2), absence of comorbidities (adjusted odds ratio = 1.8, 95% confidence interval: 1.1 and 3.1), adequate knowledge about hypertension (adjusted odds ratio = 4.7, 95% confidence interval: 2.5 and 8.8), good social support (adjusted odds ratio = 2.7, 95% confidence interval: 1.6 and 4.7), and being khat abstainer (adjusted odds ratio = 1.9, 95% confidence interval: 1.1 and 3.5) were significantly associated with good self-care practice. Conclusion: The prevalence of good self-care practice was low. In this study, good self-care practice was significantly associated with age, formal education, comorbidities, knowledge about hypertension, social support, and current khat chewing condition. Regular check-up and follow-up of patients’ compliance with self-management protocol, and more emphasis should be given to identify factors that potentially impeding patients’ adherence to hypertension self-management protocol.
Graduating With Honors in Resilience: Creating a Whole New Doctor
Authors: Mikhaiel John Paul , Pollack Jack , Buck Emory , Williams Matt , Lott Aisha , Penner John C , Ann Cary Margaret 
Published: December 2020

Background Although coaching programs have become a prominent piece of graduate medical education, they have yet to become an integral part of undergraduate medical education. A handful of medical schools have utilized longitudinal coaching experiences as a method for professional identity formation, developing emotional intelligence and leadership. Objective We developed A Whole New Doctor (AWND), a medical student leadership development and coaching program at Georgetown University, with the aim of fostering resilience, leadership, and emotional intelligence at the nascent stage of physician training. To our knowledge, ours is the only program that is largely student-managed and uses certified executive coaches in the medical student population. Methods Cohort 1 of AWND started in October 2016. For each cohort, we hold a kickoff workshop that is highly interactive, fast-paced and covers coaching, complex thinking, reflective writing, and a coaching panel for Q&A. Following the workshop, students work with coaches individually to address self-identified weaknesses, tensions, and areas of conflict. We believe the program’s student-driven nature provides a new structural approach to professional development and leadership programs, offering students a simultaneously reflective and growth-oriented opportunity to develop essential non-technical skills for physician leaders. Results Of the 132 students in the program, 107 have worked with one of our coaches (81%). Student testimonials have been uniformly positive with students remarking on an increased sense of presence, improvements in communication, and more specific direction in their careers. Conclusion Our pilot coaching program has received positive feedback from students early in their medical training. It will be important to further scale the program to reach an increasing number of students and quantitatively evaluate participants for the long-term effects of our interventions.
Interrater Agreement of an Arthroscopic Anterior Cruciate Ligament Tear Classification System
Authors:   BEAR-MOON, Vega José F. , Strnad Gregory J. , Briskin Isaac , Cox Charles L. , Farrow Lutul D. , Fadale Paul , Flanigan David , Hulstyn Michael , Imrey Peter B. , Kaeding Christopher C. , Owens Brett D. , Saluan Paul , Wright Rick , Yen Yi-Meng , Spindler Kurt P. 
Published: December 2020

Background: Anterior cruciate ligament (ACL) rupture is the most common ligament injury treated surgically by orthopaedic surgeons. The gold standard for the treatment of the majority of primary ACL tears is ACL reconstruction. However, novel methods of repair, such as bridge-enhanced ACL repair (BEAR), are currently being investigated as alternatives to reconstruction. To assess patients for midsubstance repair suitability, clarify the prognostic implications of injury location and damage, and evaluate the results of a repair technique, it is important to have a baseline classification system or grading scale that is reproducible across surgeons, particularly for multicenter collaboration. Currently, no such system or scale exists. Purpose: To develop an arthroscopic ACL tear classification system and to evaluate its interobserver reliability. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: Eleven fellowship-trained orthopaedic surgeon investigators reviewed 75 video clips containing arthroscopic evaluation of a torn ACL and then completed the 6-question ACL Pathology Evaluation Form. Agreement statistics including exact agreement, Fleiss κ, Gwet agreement coefficient 1 (AC1), and Gwet AC2 were then calculated to assess interobserver reliability. Results: In aggregate, the multiple assessments of observer reproducibility revealed that surgeon participants in this study, when evaluating the same injury, agreed roughly 80% of the time on whether (1) at least 50% of the tibial footprint remained, (2) the remaining tibial stump was ≥10 mm, and (3) the injury was therefore reparable using the BEAR procedure. Participants also agreed roughly 60% of the time on exactly how many suturable bundles were available. These characteristics are believed to be most important, among those studied, in determining whether a torn ACL is amenable to midsubstance repair. Conclusion: This study is the first of its kind to demonstrate the interobserver reliability of arthroscopic classification of ACL tears. We have demonstrated that this classification system, though not ideally reproducible, is reliable enough across surgeons at multiple institutions for use in multicenter studies. Registration: NCT03776162 ( ClinicalTrials.gov identifier).
CRISPR screen identifies genes that sensitize AML cells to double-negative T-cell therapy
Authors: Soares Fraser , Chen Branson , Lee Jong Bok , Ahmed Musaddeque , Ly Dalam , Tin Enoch , Kang Hyeonjeong , Zeng Yong , Akhtar Nayeema , Minden Mark D. , He Housheng Hansen , Zhang Li 
Published: December 2020

Abstract
Acute myeloid leukemia (AML) remains a devastating disease in need of new therapies to improve patient survival. Targeted adoptive T-cell therapies have achieved impressive clinical outcomes in some B-cell leukemias and lymphomas but not in AML. Double-negative T cells (DNTs) effectively kill blast cells from the majority of AML patients and are now being tested in clinical trials. However, AML blasts obtained from ∼30% of patients show resistance to DNT-mediated cytotoxicity; the markers or mechanisms underlying this resistance have not been elucidated. Here, we used a targeted clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) screen to identify genes that cause susceptibility of AML cells to DNT therapy. Inactivation of the Spt-Ada-Gcn5-acetyltransferase (SAGA) deubiquitinating complex components sensitized AML cells to DNT-mediated cytotoxicity. In contrast, CD64 inactivation resulted in resistance to DNT-mediated cytotoxicity. Importantly, the level of CD64 expression correlated strongly with the sensitivity of AML cells to DNT treatment. Furthermore, the ectopic expression of CD64 overcame AML resistance to DNTs in vitro and in vivo. Altogether, our data demonstrate the utility of CRISPR/Cas9 screens to uncover mechanisms underlying the sensitivity to DNT therapy and suggest CD64 as a predictive marker for response in AML patients.
Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors
Authors: Dunbar Andrew , Bolton Kelly L. , Devlin Sean M. , Sanchez-Vega Francisco , Gao Jianjiong , Mones Jodi V. , Wills Jonathan , Kelly Daniel , Farina Mirko , Cordner Keith B. , Park Young , Kishore Sirish , Juluru Krishna , Iyengar Neil M. , Levine Ross L. , Zehir Ahmet , Park Wungki , Khorana Alok A. , Soff Gerald A. , Mantha Simon 
Published: December 2020

Abstract
Venous thromboembolism (VTE) associated with cancer (CAT) is a well-described complication of cancer and a leading cause of death in patients with cancer. The purpose of this study was to assess potential associations of molecular signatures with CAT, including tumor-specific mutations and the presence of clonal hematopoiesis. We analyzed deep-coverage targeted DNA-sequencing data of &gt;14 000 solid tumor samples using the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets platform to identify somatic alterations associated with VTE. End point was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis. Cause-specific Cox proportional hazards regression was used, adjusting for pertinent clinical covariates. Of 11 695 evaluable individuals, 72% had metastatic disease at time of analysis. Tumor-specific mutations in KRAS (hazard ratio [HR], 1.34; 95% confidence interval (CI), 1.09-1.64; adjusted P = .08), STK11 (HR, 2.12; 95% CI, 1.55-2.89; adjusted P &lt; .001), KEAP1 (HR, 1.84; 95% CI, 1.21-2.79; adjusted P = .07), CTNNB1 (HR, 1.73; 95% CI, 1.15-2.60; adjusted P = .09), CDKN2B (HR, 1.45; 95% CI, 1.13-1.85; adjusted P = .07), and MET (HR, 1.83; 95% CI, 1.15-2.92; adjusted P = .09) were associated with a significantly increased risk of CAT independent of tumor type. Mutations in SETD2 were associated with a decreased risk of CAT (HR, 0.35; 95% CI, 0.16-0.79; adjusted P = .09). The presence of clonal hematopoiesis was not associated with an increased VTE rate. This is the first large-scale analysis to elucidate tumor-specific genomic events associated with CAT. Somatic tumor mutations of STK11, KRAS, CTNNB1, KEAP1, CDKN2B, and MET were associated with an increased risk of VTE in patients with solid tumors. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types.
Clinical effects of administering leukemia-specific donor T cells to patients with AML/MDS after allogeneic transplant
Authors: Lulla Premal D. , Naik Swati , Vasileiou Spyridoula , Tzannou Ifigeneia , Watanabe Ayumi , Kuvalekar Manik , Lulla Suhasini , Carrum George , Ramos Carlos A. , Kamble Rammurti , Hill LaQuisa , Randhawa Jasleen , Gottschalk Stephen , Krance Robert , Wang Tao , Wu Mengfen , Robertson Catherine , Gee Adrian P. , Chung Betty , Grilley Bambi , Brenner Malcolm K. , Heslop Helen E. , Vera Juan F. , Leen Ann M. 
Published: December 2020

Abstract
Relapse after allogeneic hematopoietic stem cell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Infusion of unselected donor lymphocytes (DLIs) enhances the graft-versus-leukemia (GVL) effect. However, because the infused lymphocytes are not selected for leukemia specificity, the GVL effect is often accompanied by life-threatening graft-versus-host disease (GVHD), related to the concurrent transfer of alloreactive lymphocytes. Thus, to minimize GVHD and maximize GVL, we selectively activated and expanded stem cell donor–derived T cells reactive to multiple antigens expressed by AML/MDS cells (PRAME, WT1, Survivin, and NY-ESO-1). Products that demonstrated leukemia antigen specificity were generated from 29 HCT donors. In contrast to DLIs, leukemia-specific T cells (mLSTs) selectively recognized and killed leukemia antigen–pulsed cells, with no activity against recipient's normal cells in vitro. We administered escalating doses of mLSTs (0.5 to 10 × 107 cells per square meter) to 25 trial enrollees, 17 with high risk of relapse and 8 with relapsed disease. Infusions were well tolerated with no grade &gt;2 acute or extensive chronic GVHD seen. We observed antileukemia effects in vivo that translated into not-yet-reached median leukemia-free and overall survival at 1.9 years of follow-up and objective responses in the active disease cohort (1 complete response and 1 partial response). In summary, mLSTs are safe and promising for the prevention and treatment of AML/MDS after HCT. This trial is registered at www.clinicaltrials.com as #NCT02494167.
The prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures prior to FVIII inhibitor development
Authors: Reipert B. M. , Gangadharan B. , Hofbauer C. J. , Berg V. , Schweiger H. , Bowen J. , Blatny J. , Fijnvandraat K. , Mullins E. S. , Klintman J. , Male C. , McGuinn C. , Meeks S. L. , Radulescu V. C. , Ragni M. V. , Recht M. , Shapiro A. D. , Staber J. M. , Yaish H. M. , Santagostino E. , Brown D. L. 
Published: December 2020

Abstract
Preventing factor VIII (FVIII) inhibitors following replacement therapies with FVIII products in patients with hemophilia A remains an unmet medical need. Better understanding of the early events of evolving FVIII inhibitors is essential for risk identification and the design of novel strategies to prevent inhibitor development. The Hemophilia Inhibitor Previously Untreated Patients (PUPs) Study (HIPS; www.clinicaltrials.gov #NCT01652027) is the first prospective cohort study to evaluate comprehensive changes in the immune system during the first 50 exposure days (EDs) to FVIII in patients with severe hemophilia A. HIPS participants were enrolled prior to their first exposure to FVIII or blood products (“true PUPs”) and were evaluated for different immunological and clinical parameters at specified time points during their first 50 EDs to a single source of recombinant FVIII. Longitudinal antibody data resulting from this study indicate that there are 4 subgroups of patients expressing distinct signatures of FVIII-binding antibodies. Subgroup 1 did not develop any detectable FVIII-binding immunoglobulin G (IgG) antibodies. Subgroup 2 developed nonneutralizing, FVIII-binding IgG1 antibodies, but other FVIII-binding IgG subclasses were not observed. Subgroup 3 developed transient FVIII inhibitors associated with FVIII-binding IgG1 antibodies, similar to subgroup 2. Subgroup 4 developed persistent FVIII inhibitors associated with an initial development of high-affinity, FVIII-binding IgG1 antibodies, followed by IgG3 and IgG4 antibodies. Appearance of FVIII-binding IgG3 was always associated with persistent FVIII inhibitors and the subsequent development of FVIII-binding IgG4. Some of the antibody signatures identified in HIPS could serve as candidates for early biomarkers of FVIII inhibitor development.