bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Xa Activity Monitoring for Optimizing Rivaroxaban Dosage in Chinese Patients with Cerebral Venous Thrombosis
Authors: Zhang Xiaoming , Gao Meini , Lan Duo , Wang Zhongao , Fang Kun , Ren Xiangyu , Liu Naiqi , Zhou Da , Ji Xunming , Meng Ran 
Published: September 2024

Background Rivaroxaban, a direct Factor Xa inhibitor, is commonly used for cerebral venous thrombosis (CVT) correction. However, pharmacokinetic differences in Chinese may vary in sensitivity and tolerance, resulting in either insufficient or excessive anticoagulation. Herein, the optimizing dosages of rivaroxaban in Chinese patients with CVT were analyzed based on monitoring anti-Xa activity dynamically, to maintain therapeutic efficacy and reduce rivaroxaban-related bleeding. Methods A real-world cohort study was conducted involving 112 CVT patients in Xuanwu Hospital, from August 2021 through January 2024. Patients were grouped according to their doses of rivaroxaban use (5, 10, 15, and 20 mg daily) based on dynamic plasma anti-Xa activity monitored using the chromogenic anti-Xa assay. Plasma levels of anti-Xa activity reached the therapeutic range, bleeding events and the dosage of rivaroxaban among these groups were analyzed. Results The ratios of the patients whose plasma anti-Xa levels reached the standard therapeutic level (0.3–0.7 IU/mL) between the cohorts less than 20 mg/d and 20 mg/d showed no statistical difference, and no significant disparities were observed among 5, 10, 15, and 20 mg/d dose groups. There was a discernible increase in the proportion of patients with bleeding events in the 20 mg/d group, even though the results did not reach a statistical difference. Meanwhile, in patients with bleeding events, their plasma anti-Xa levels could exceed 0.7 IU/mL. Conclusion Sensitivity and tolerance to rivaroxaban in Chinese may vary. Individualized therapy dosage under the guidance of anti-Xa activity monitoring may not only guarantee anticoagulation effect, but also reduce rivaroxaban-related bleeding events.
Higher 10-Year Survival with Breast-Conserving Therapy over Mastectomy for Women with Early-Stage (I-II) Breast Cancer: Analysis of the CDC Patterns of Care Data Base
Authors: Shrestha Pratibha , Hsieh Mei-Chin , Ferguson Tekeda , Peters Edward S , Trapido Edward , Yu Qingzhao , Chu Quyen D , Wu Xiao-Cheng 
Published: September 2024

Background: Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC). Objective: To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival. Design: Cohort study. Methods: We analyzed data on women aged 20 years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding. Results: Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR = 1.22, 95% CI = [1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR = 1.26, 95% CI = [1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD ( P < .05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates. Conclusion: ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients.
Serum Albumin as a Prognostic Biomarker for Febrile Neutropenia Outcome and Complications: A Prospective Observational Trial
Authors: Dimitrijević Jelena , Čalamać Marina , Đurmez Ognjen , Krstić Danijela , Stojanović Marko 
Published: September 2024

Background: Febrile neutropenia (FN) poses a significant challenge in cancer treatment, with a high incidence among patients undergoing standard therapies. Predicting FN complications and outcomes remains crucial for improving patient management strategies. Biomarkers, including procalcitonin and albumin, have garnered attention for their potential prognostic value in FN. Methods: We conducted a prospective observational study at a tertiary hospital, enrolling 185 adult cancer patients experiencing FN episodes. We assessed serum albumin levels and incorporated them into the Multinational Association for Supportive Care in Cancer (MASCC) risk index to enhance risk stratification. Results: Serum albumin levels displayed promising prognostic utility in febrile neutropenia (FN). They exhibited moderate specificity and sensitivity in predicting mortality during FN and 28-day mortality. Serum albumin levels were significantly associated with gastrointestinal infections, serving as an independent predictor. Integrating serum albumin into the MASCC risk index improved predictive accuracy for FN mortality by 50%, 28-day mortality by 66.67%, and respiratory tract infections by 62.50%, enhancing in this way risk stratification for FN-related complications. Conclusion: Serum albumin emerges as a promising biomarker for prognostication in FN, complementing existing risk assessment frameworks. Its incorporation into the MASCC risk index enhances predictive capabilities, aiding clinicians in identifying high-risk patients promptly. While albumin shows potential in predicting mortality and complications, further research is warranted to optimize sensitivity and specificity, ensuring its clinical utility.
Is the ulnar fovea sign positive only in foveal tears of the triangular fibrocartilage complex?
Authors: Choudhury Muntasir Mannan , Ling Angeline Aw Ai , Yap Robert Tze Jin 
Published: September 2024

A positive ulnar fovea sign is usually considered to be specific for foveal disruption of the distal radioulnar ligaments. A retrospective review was done of 73 patients with a positive ulnar fovea sign. Only 21 patients had a foveal tear on arthroscopic examination. Level of evidence: IV
The Impact of COVID-19 Service Learning on Medical Student Professional Identity Formation
Authors: Lu Wei-Hsin , Pang Lindsy , Strano-Paul Lisa 
Published: September 2024

OBJECTIVE The COVID-19 pandemic affected in-person educational activities and required medical schools to adapt and enrich their curriculum to ensure ongoing professional development. During the height of the COVID-19 pandemic, students expressed a significant desire to contribute and continue their medical education. Service learning promotes experiential learning and Professional Identity Formation (PIF). This study examines the impact that a service-learning elective had on medical students’ education and PIF. METHODS Offering a service-learning elective allowed students to remain engaged in educational activities and pandemic-relief efforts. We conducted a qualitative analysis of 132 written reflections by medical students who completed a 2- or a 4-week service-learning elective to assess for major themes and impact on PIF. RESULTS Participation in service learning had a favorable impact on PIF as expressed by the personal qualities student identified as having developed or improved upon because of their participation. Enhancement of communication skills, teamwork skills, compassion, and empathy were major themes conveyed in student reflections. Qualities of resilience were also portrayed through the write-up as students noted how the elective allowed for active engagement in community pandemic-relief efforts and created opportunities for overcoming obstacles related to service learning projects they participated in. CONCLUSIONS Service learning in medical school has a dual purpose of providing community support while imparting significant learning opportunities for PIF in medical students.
The current landscape of frontline large B-cell lymphoma trials
Authors: Qualls David , Armand Philippe , Salles Gilles 
Published: September 2024

Abstract
At least 25% to 35% of patients with large B-cell lymphoma (LBCL) are not cured with frontline treatment, with generally poor subsequent outcomes. This motivates ongoing and intense interest in improving the frontline treatment of this disease. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has remained the standard of care for 20 years despite dozens of trials aiming to improve upon this regimen, and only recently has a novel regimen (pola-R-CHP [polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone]) challenged its supremacy. Fortunately, at least 15 promising randomized trials evaluating new treatments in frontline LBCL treatment are underway. They differ not only in the therapy evaluated in the experimental arm, but in the choice of control arm, primary end point, and patient selection strategy, with some targeting specific biologic subtypes, some focusing on specific high-risk patient populations, and others enrolling older or frail patients. Novel response-adapted strategies leveraging circulating tumor DNA are also underway. Although this variety of approaches provides a welcome increase in the overall likelihood of success, it will also present challenges if several of these trials are successful and we must choose among multiple potential treatment options that were not all tested in the same fashion. In this review, we summarize the main ongoing frontline randomized trials and discuss some of the questions that we will face in interpreting and applying their results in clinical practice in the next few years.
Disruption of cotranscriptional splicing suggests RBM39 is a therapeutic target in acute lymphoblastic leukemia
Authors: Jin Qi , Harris Ethan , Myers Jacquelyn A. , Mehmood Rashid , Cotton Anitria , Shirnekhi Hazheen K. , Baggett David W. , Wen Jeremy Qiang , Schild Andrew B. , Bhansali Rahul S. , Klein Jonathon , Narina Shilpa , Pieters Tim , Yoshimi Akihide , Pruett-Miller Shondra M. , Kriwacki Richard , Abdel-Wahab Omar , Malinge Sebastien , Ntziachristos Panagiotis , Obeng Esther A. , Crispino John D. 
Published: September 2024

Abstract
There are only a few options for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), thus, this is a major area of unmet medical need. In this study, we reveal that the inclusion of a poison exon in RBM39, which could be induced by both CDK9 or CDK9 independent cyclin-dependent kinases, mitogen-activated protein kinases, glycogen synthase kinases, CDC-like kinases (CMGC) kinase inhibition, is recognized by the nonsense-mediated messenger RNA decay pathway for degradation. Targeting this poison exon in RBM39 with CMGC inhibitors led to protein downregulation and the inhibition of ALL growth, particularly in relapsed/refractory B-ALL. Mechanistically, disruption of cotranscriptional splicing by the inhibition of CMGC kinases, including DYRK1A, or inhibition of CDK9, which phosphorylate the C-terminal domain of RNA polymerase II (Pol II), led to alteration in the SF3B1 and Pol II association. Disruption of SF3B1 and the transcriptional elongation complex altered Pol II pausing, which promoted the inclusion of a poison exon in RBM39. Moreover, RBM39 ablation suppressed the growth of human B-ALL, and targeting RBM39 with sulfonamides, which degrade RBM39 protein, showed strong antitumor activity in preclinical models. Our data reveal that relapsed/refractory B-ALL is susceptible to pharmacologic and genetic inhibition of RBM39 and provide 2 potential strategies to target this axis.
Focal deletions of a promoter tether activate the IRX3 oncogene in T-cell acute lymphoblastic leukemia
Authors: Rahman Sunniyat , Bloye Gianna , Farah Nadine , Demeulemeester Jonas , Costa Joana R. , O’Connor David , Pocock Rachael , Rapoz-D’Silva Tanya , Turna Adam , Wang Lingyi , Lee SooWah , Fielding Adele K. , Roels Juliette , Jaksik Roman , Dawidowska Małgorzata , Van Vlierberghe Pieter , Hadjur Suzana , Hughes Jim R. , Davies James O. J. , Gutierrez Alejandro , Kelliher Michelle A. , Van Loo Peter , Dawson Mark A. , Mansour Marc R. 
Published: September 2024

Abstract
Oncogenes can be activated in cis through multiple mechanisms including enhancer hijacking events and noncoding mutations that create enhancers or promoters de novo. These paradigms have helped parse somatic variation of noncoding cancer genomes, thereby providing a rationale to identify noncanonical mechanisms of gene activation. Here we describe a novel mechanism of oncogene activation whereby focal copy number loss of an intronic element within the FTO gene leads to aberrant expression of IRX3, an oncogene in T-cell acute lymphoblastic leukemia (T-ALL). Loss of this CTCF-bound element downstream to IRX3 (+224 kb) leads to enhancer hijack of an upstream developmentally active super-enhancer of the CRNDE long noncoding RNA (−644 kb). Unexpectedly, the CRNDE super-enhancer interacts with the IRX3 promoter with no transcriptional output until it is untethered from the FTO intronic site. We propose that “promoter tethering” of oncogenes to inert regions of the genome is a previously unappreciated biological mechanism preventing tumorigenesis.
Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutations
Authors: Gutierrez-Rodrigues Fernanda , Groarke Emma M. , Thongon Natthakan , Rodriguez-Sevilla Juan Jose , Catto Luiz Fernando B. , Niewisch Marena R. , Shalhoub Ruba , McReynolds Lisa J. , Clé Diego V. , Patel Bhavisha A. , Ma Xiaoyang , Hironaka Dalton , Donaires Flávia S. , Spitofsky Nina , Santana Barbara A. , Lai Tsung-Po , Alemu Lemlem , Kajigaya Sachiko , Darden Ivana , Zhou Weiyin , Browne Paul V. , Paul Subrata , Lack Justin , Young David J. , DiNardo Courtney D. , Aviv Abraham , Ma Feiyang , De Oliveira Michel Michels , de Azambuja Ana Paula , Dunbar Cynthia E. , Olszewska Malgorzata , Olivier Emmanuel , Papapetrou Eirini P. , Giri Neelam , Alter Blanche P. , Bonfim Carmem , Wu Colin O. , Garcia-Manero Guillermo , Savage Sharon A. , Young Neal S. , Colla Simona , Calado Rodrigo T. 
Published: September 2024

Abstract
Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype. CH occurred predominantly in symptomatic patients and in signature genes typically associated with cancers: PPM1D, POT1, TERT promoter (TERTp), U2AF1S34, and/or TP53. Chromosome 1q gain (Chr1q+) was the commonest karyotypic abnormality. Clinically, multiorgan involvement and CH in TERTp, TP53, and splicing factor genes were associated with poorer overall survival. Chr1q+ and splicing factor or TP53 mutations significantly increased the risk of hematologic malignancies, regardless of clonal burden. Chr1q+ and U2AF1S34 mutated clones were premalignant events associated with the secondary acquisition of mutations in genes related to hematologic malignancies. Similar to the known effects of Chr1q+ and TP53-CH, functional studies demonstrated that U2AF1S34 mutations primarily compensated for aberrant upregulation of TP53 and interferon pathways in telomere-dysfunctional hematopoietic stem cells, highlighting the TP53 pathway as a canonical route of malignancy in TBD. In contrast, somatic POT1/PPM1D/TERTp mutations had distinct trajectories unrelated to cancer development. With implications beyond TBD, our data show that telomere dysfunction is a strong selective pressure for CH. In TBD, CH is a poor prognostic marker associated with worse overall survival. The identification of key regulatory pathways that drive clonal transformation in TBD allows for the identification of patients at a higher risk of cancer development.
A weekly low-dose regimen of decitabine and venetoclax is efficacious and less myelotoxic in a racially diverse cohort
Authors: Goldfinger Mendel , Mantzaris Ioannis , Shastri Aditi , Saunthararajah Yogen , Gritsman Kira , Sica R. Alejandro , Kornblum Noah , Shah Nishi , Levitz David , Rockwell Bradley , Shapiro Lauren C. , Gupta Ridhi , Pradhan Kith , Xue Xiaonan , Munoz Anne , Dhawan Aradhika , Fehn Karen , Comas Monica , Verceles Jhannine Alyssa , Jonas Brian A. , Kambhampati Suman , Shi Yang , Braunschweig Ira , Cooper Dennis L. , Konopleva Marina , Feldman Eric J. , Verma Amit 
Published: September 2024

Abstract
A metronomic, low-dose schedule of decitabine and venetoclax was safe and effective in myeloid malignancies with few dose reductions or interruptions in an older diverse population. Median overall survival for patients with acute myeloid leukemia and a TP53-mutation was 16.1 and 11.3 months, respectively. This trial was registered at www.clinicaltrials.gov as #NCT05184842.
Pretransplant MRD detection of fusion transcripts is strongly prognostic in KMT2A-rearranged acute myeloid leukemia
Authors: Loo Sun , Potter Nicola , Ivey Adam , O’Nions Jenny , Moon Roderick , Jovanovic Jelena , Fong Chun Y. , Anstee Natasha S. , Tiong Ing Soo , Othman Jad , Chua Chong Chyn , Renshaw Hanna , Baker Robert , Fleming Shaun , Russell Nigel H. , Ritchie David , Bajel Ashish , Hou Hsin-An , Dillon Richard , Wei Andrew H. 
Published: September 2024

Abstract
Pretransplant detection of KMT2Ar measurable residual disease ≥0.001% by quantitative polymerase chain reaction was associated with significantly inferior posttransplant survival (2-year relapse-free survival 17% vs 59%; P = .001) and increased 2-year cumulative incidence of relapse (75% vs 25%, P = .0004).
Neurodevelopmental outcome at two years of age and predictive value of General Movement Assessment in infants exposed to alcohol and/or drugs during pregnancy: a prospective cohort study
Authors: Fjørtoft Toril , Brandal Merethe , Adde Lars , Osland Siril , Rygh Hilde , Ustad Tordis , Evensen Kari Anne I. 
Published: September 2024

Abstract
Background
Exposure to alcohol and/or other addictive drugs in pregnancy is a documented risk factor for neurological impairment. We aimed to assess neurodevelopmental outcome at two years of age in infants exposed to prenatal alcohol and/or other addictive drugs and to examine the predictive value of early motor assessment.

Methods
This was a follow-up at two years of age in the prospective cohort study Children Exposed to Alcohol and/or Drugs in Intrauterine Life (CEADIL). The exposed group comprised 73 infants recruited from primary health care and included in a hospital follow-up programme at St. Olavs Hospital, Trondheim University Hospital, Norway. The control group comprised 93 healthy, unexposed infants recruited from the maternity ward at the same hospital. All children had been assessed by physiotherapists using the General Movement Assessment (GMA) at three months of age. Presence of fidgety movements, movement character and the Motor Optimality Score – Revised (MOS-R) were used. At two years of age, the children were assessed by trained examiners using the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III), Ages & Stages Questionnaires: Social-Emotional (ASQ:SE) and the Hollingshead Two-Factor Index of Social Position (SES).

Results
The cognitive, language and motor composite scores of BSID-III were considerably lower in the exposed group than in the control group. Mean differences adjusted for age and parental SES ranged from − 13.3 (95% confidence interval, CI: -18.6 to -8.0) to -17.7 (95% CI: -23.3 to -12.2). Suboptimal fidgety movements and monotonous movement character had high sensitivity (0.94 to 0.74), but low specificity (0.10 to 0.32), while sensitivity and specificity of the MOS-R was around 50 and 60%, respectively.

Conclusions
Neurodevelopmental outcome at two years of age was poorer in a group of children exposed to alcohol and/or drugs in pregnancy compared with a control group of healthy, unexposed children. Sensitivity of suboptimal fidgety movements and monotonous movement character at three months of age for later neurodevelopmental outcome was high to acceptable, but the MOS-R had limited sensitivity.
Prevalence and short-term clinical impacts of new-onset diabetes mellitus among patients with COVID-19 in jazan region, Saudi Arabia
Authors: Mohamed Amal H. , Darraj Majid , Yassin Abuobaida , Somaili Mohammed , Sayed Ahmed , Oraibi Omar , Mohrag Mostafa , Madkhali Mohammed Ali , Alqassimi Sameer , Madkhali Mohammed A. 
Published: September 2024

Abstract
Background
Diabetes Mellitus is a major predictor for severity and mortality that is increased by 50% in COVID-19 infection. The aim of this study is to estimate the prevalence of new-onset DM among patients with COVID-19 and examined the short clinical outcomes of the disease.

Method
This is a retrospective study of revising electronic medical records to assess the prevalence of new-onset DM in COVID-19 patients and its impact on the severity of the disease. Adult patients with confirmed COVID-19 during the period from June 2020 to December 2021 were enrolled.

Results
725 patients were included. 53.8% of them were males and 46.2 were females, the mean age was 43.35 ± 16.76. 13.2% were diabetics; 2.2% with preexisting DM and 11.0% had new-onset DM. 6.34% had coexisting medical conditions. DKA at presentation was observed in 6 patients (0.8%) of newly diagnosed DM. There is a significant correlation between age and family history (FH), and BMI and new-onset DM (P < 0.05). The overall mortality rate was 2.2%, and it was significantly higher in diabetics in comparison to non-diabetics (P < 0.001). 8.6% had persistent hyperglycemia after 4 months of follow-up.

Conclusion
The prevalence of COVID-19 related new-onset DM was correlated significantly with disease severity and mortality rate. Age, FH, and BMI, were the major predictors. We recommend that frequent monitoring of blood glucose for patients with COVID-19 infections to detect DM, therefore, prompt treatment can be initiated.