bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canonical and Nuclear mTOR Specify Distinct Transcriptional Programs in Androgen-Dependent Prostate Cancer Cells
Authors: Chen Yonghong , Han Lingwei , Dufour Catherine Rosa , Alfonso Anthony , Giguère Vincent 
Published: October 2023

Abstract

mTOR is a serine/threonine kinase that controls prostate cancer cell growth in part by regulating gene programs associated with metabolic and cell proliferation pathways. mTOR-mediated control of gene expression can be achieved via phosphorylation of transcription factors, leading to changes in their cellular localization and activities. mTOR also directly associates with chromatin in complex with transcriptional regulators, including the androgen receptor (AR). Nuclear mTOR (nmTOR) has been previously shown to act as a transcriptional integrator of the androgen signaling pathway in association with the chromatin remodeling machinery, AR, and FOXA1. However, the contribution of cytoplasmic mTOR (cmTOR) and nmTOR and the role played by FOXA1 in this process remains to be explored. Herein, we engineered cells expressing mTOR tagged with nuclear localization and export signals dictating mTOR localization. Transcriptome profiling in AR-positive prostate cancer cells revealed that nmTOR generally downregulates a subset of the androgen response pathway independently of its kinase activity, while cmTOR upregulates a cell cycle–related gene signature in a kinase-dependent manner. Biochemical and genome-wide transcriptomic analyses demonstrate that nmTOR functionally interacts with AR and FOXA1. Ablation of FOXA1 reprograms the nmTOR cistrome and transcriptome of androgen responsive prostate cancer cells. This works highlights a transcriptional regulatory pathway in which direct interactions between nmTOR, AR and FOXA1 dictate a combinatorial role for these factors in the control of specific gene programs in prostate cancer cells.

Implications:
The finding that canonical and nuclear mTOR signaling pathways control distinct gene programs opens therapeutic opportunities to modulate mTOR activity in prostate cancer cells.
Chance Combinatorics: The Theory that History Forgot
Authors: Norton John D. 
Published: October 2023

Abstract
Seventeenth-century “chance combinatorics” was a self-contained theory. It had an objective notion of chance derived from physical devices with chance properties, such as casts of dice, combinatorics to count chances and, to interpret their significance, a rule for converting these counts into fair wagers. It lacked a notion of chance as a measure of belief, a precise way to connect chance counts with frequencies and a way to compare chances across different games. These omissions were not needed for the theory’s interpretation of chance counts: determining which are fair wagers. The theory provided a model for how indefinitenesses could be treated with mathematical precision in a special case and stimulated efforts to seek a broader theory.
Redescription of Irodes callionymi (Yamaguti, 1939) (Copepoda, Cyclopoida, Taeniacanthidae) recovered from Synchiropus altivelis (Temminck & Schlegel, 1845) (Actinopterygii) in Japan, with description of the male and copepodids V and IV
Authors: Izawa Kunihiko 
Published: October 2023

Abstract
Irodes callionymi (Yamaguti, 1939) is redescribed based on specimens of both sexes recovered from the bucco-branchial cavity and the body surface of Synchiropus altivelis (Temminck & Schlegel, 1845) (Callionymidae) in Japan. The male, as well as copepodids V and IV are described for the first time for the species.
Research on genetic diversity and population structure of Capitulum mitella in the Western Taiwan Strait based on mitochondrial 16S rRNA sequences
Authors: Xing Bingpeng , Wu Qiong , Zhou Qianqian , Liu Siwei , Sun Rouxin , Chen Xiaoyin , Xiang Peng , Wang Chunguang , Wang Yanguo 
Published: October 2023

Abstract
Capitulum mitella is an important species in the intertidal ecosystem and in the economy in China. This study explored the genetic diversity and population structure of C. mitella using mitochondrial 16S ribosomal subunit (16S rRNA) gene sequences. The researchers sequenced a 527 bp fragment of 16S rRNA from 390 samples collected from six localities along Western Taiwan Strait and identified 45 distinct haplotypes with an average haplotype diversity (h) of 0.451 and an average nucleotide diversity (π) of 0.00124. The pairwise statistics and AMOVA indicated a lack of significant population structure. The results indicated a recent expansion of the population of C. mitella in the study area. This expansion, combined with the species’ high dispersal capabilities, limited physical barriers, and the influence of oceanic currents, may be the factors contributing to its current phylogeographic structure. This study provides particularly important information for managing and protecting the resources of C. mitella in Southern China.
Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer
Authors: Hageman Elizabeth , Lussier Mia E. 
Published: October 2023

Objective: This article aims to discuss elacestrant, an oral selective estrogen receptor downregulator approved by the Food and Drug Administration (FDA) in January 2023 for the treatment of hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer. Data sources: PubMed, Embase, Medline, Clinicaltrials.gov, and the National Comprehensive Cancer Network (NCCN) were searched from inception to August 31, 2023. Study selection and data extraction: Clinical trials published in English were included and relevant information regarding methodology and results were extracted. Data synthesis: Phase 1 and 3 trials showed elacestrant was safe and improved progression-free survival in patients with endocrine receptor 1 (ESR1) mutations who failed cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) plus 1 prior endocrine therapy compared with standard of care (SOC) (fulvestrant, anastrozole, letrozole, or exemestane monotherapy). Relevance to patient care and clinical practice in comparison to existing drugs: Elacestrant maintains a comparable adverse event profile with other endocrine therapies and offers an alternative to typical sequential therapy which can delay the use of or be used after traditional chemotherapy. Elacestrant is currently being studied in CDK 4/6 inhibitor naïve patients and as a component of combination therapy for first-line use which could lead to future indications. Conclusions: Elacestrant gained FDA approval in January 2023 and can be considered in patients with HR+ HER2− advanced breast cancer and ESR1 mutations who have progressed despite therapy with either CDK 4/6i plus aromatase inhibitors (AI) or fulvestrant or chemotherapy.
Talent Development versus Talent Management: Unblurring the Lines for Workforce and Organizational Performance
Authors: Osolase Ehikioya H. , Mohd Rasdi Roziah , Mansor Zuraina D. 
Published: October 2023

The Problem In reference to workforce development for organizational performance, the blurry lines between talent development and talent management have resulted to several HRD scholars interchangeably using talent management in replacement of talent development. However, talent development as an HRD function supersedes talent management. Therefore, to demarcate the existing lines which exists between both, it is important that HRD practitioners develop the required awareness. The Solution Talent development is a necessity for efficient management of people. To bring about a fundamental change on the need to clearly differentiate between talent development and talent management, the expertise of HRD practitioners in collaboration with industry professionals, is required to develop new knowledge and models for workforce and organizational performance. The Stakeholders Scholars and practitioners of human resource development and other fields within the management discipline, in addition to managers and the workforce across all sectors in various industries.
Chronic illness and psychological problems in emerging adults: Moderation by perceived parental distress
Authors: Kukay Abigail , McKinney Cliff 
Published: October 2023

Objective The aim of the current study was to better understand if perceived parental distress moderates the effects of having a chronic illness and poor physical quality of life on psychological problems reported by emerging adults. Methods Participants consisted of 538 college-attending emerging adults (53.5% women; 46.5% men). Participants completed an online study that was composed of questions regarding chronic illness, the World Health Organization Quality of Life – Brief, the Adult Self-Report scale, and the Adult Behavior Checklist. Results In both emerging adult women and men, endorsing a chronic illness is significantly associated with psychological problems. Psychological problems in both emerging adult women and men were significantly predicted by the three-way interaction between endorsing a chronic illness, physical quality of life, and perceived maternal distress. Specifically, increased perceived maternal distress was associated with higher psychological problems in both emerging adult women and men with chronic illnesses and low physical quality of life. Discussion For emerging adult women and men with a chronic illness, higher perceived maternal distress was associated with poorer psychological adjustment, while lower perceived maternal distress was associated with better psychological adjustment.
Bedside ultrasound in post-anaesthetic care unit for the diagnosis of post-extubation negative pressure pulmonary oedema: A paediatric case
Authors: Pereira Dulce , Pereira Sofia , Neves Clarinda , Segura Elena , Assunção José Pedro 
Published: October 2023

Background: Post-extubation negative pressure pulmonary oedema is a rare, potentially life-threatening complication associated with general anaesthesia. Chest radiography is used as a diagnostic tool, but it implies a non-negligible radiation exposure, a very important consideration, especially for the paediatric population. However, lung ultrasound can overcome this problem and can be used to detect postoperative pulmonary complications. Case report: A 16-year-old male was scheduled for tympanoplasty. General anaesthesia was conducted, and after extubation, the patient developed a laryngospasm. On arrival at the post-anaesthetic care unit, the patient started to cough, a pink frothy sputum and hypoxemia were noticed, and auscultation revealed crepitations. A bedside lung ultrasound showed more than three B-lines per intercostal window, suggesting an alveolar-interstitial syndrome. Discussion: With this case report, we would like to raise awareness to this clinical entity and demonstrate bedside ultrasound has an important role in the diagnostic and therapeutic assessment during the perioperative period.
Cardiovascular risk factors among Cameroonian adolescents: Comparison between public and private schools and association with physical activity practice—a cross-sectional study
Authors: Kamdem Felicite , Bika Léle Elysée Claude , Mekoulou Ndongo Jerson , Ba Hamadou , Obe Meyong Marie Ange Prisca , Fenkeu Kweban Jaff , Moussa Oumarou , Ngono Atéba Glwadys , Mouliom Sidick , Viché Lade , Ngoté Henri , Kenmegne Caroline , Ndom Ebongue Marie Solange , Djibrilla Siddikatou , Dzudié Anastase , Ménanga Alain 
Published: October 2023

Aim Cardiovascular diseases are the leading cause of death worldwide and physical activity (PA) practice is recommended as the most efficient preventive measure to curse their burden in sub-Saharan Africa. Our study aimed to compare cardiovascular risk factors (CVRFs) in adolescents in public and private schools in Cameroon and assess the impact of PA practice. Methods We conducted a cross-sectional study on students from private and public secondary schools in the city of Douala. Anthropometric parameters, blood glucose, and blood pressure (BP) were collected. PA was assessed using the short form of the International Physical Activity Questionnaire. Multivariate logistic regression was used to assess the influence of PA levels on different CVRFs. The differences were considered significant for p < .05. Results We recruited 771 participants, aged 16 ± 1years, 51.4% female, and 48.6% private school students. Prevalence of CVRFs was 38.4%; 11.5%; 5.6%; 5.4%, and 3% for overweight/obesity, abdominal obesity, smoking, glucose homeostasis abnormalities, and high BP (HBP) respectively. Around 41% of participants had low PA level (LPA). Abdominal obesity and LPA were more common among girls ( p < .0001 both) and 1.3% of participants had more than four CVRF. In multivariate analysis, LPA was significantly associated with a higher odd of HBP ( OR = 7.69; p < .0001). Conclusion The prevalence of various CVRF is high among Cameroonian adolescent schoolers. Public policies should focus on prevention programs through physical exercise and the reduction of smoking.
Intention to use PrEP among men who have sex with men and engage in chemsex: an international descriptive study
Authors: Sousa Álvaro Francisco Lopes de , Nunes Ribeiro Caíque Jordan , Santos Guilherme Reis de Santana , Oliveira Layze Braz de , Camargo Emerson Lucas Silva , Lima Shirley Verônica Melo Almeida , Oliveira Sena Inara Viviane de , Bezerra-Santos Márcio , Batista Odinéa Maria Amorim , Reis de Sousa Anderson , Mendes Isabel Amélia Costa 
Published: October 2023

Background: Pre-exposure prophylaxis (PrEP) is a valuable tool in the response to the HIV epidemic, recommended for groups with a higher risk of HIV infection, such as men who have sex with men (MSM), particularly in the context of high-risk sexual behavior such as chemsex. Purpose: This study aimed to analyze the prevalence and factors associated with the intention to use PrEP among MSM who engage in chemsex in Brazil and Portugal. Methods: This was a cross-sectional study of a secondary dataset from a larger study conducted between January 2020 and May 2021 throughout Brazil and Portugal involving 1852 MSM who engage in chemsex. An initial descriptive analysis was performed to calculate the absolute and relative frequencies of independent variables related to the intention to use PrEP among MSM. A multivariate regression model was developed to identify factors independently associated with the intention to use PrEP. Results: Although a high level of PrEP knowledge (85.75%) was observed among MSM who engage in chemsex, the prevalence of intention to use PrEP was only 59.07%. Five variables were associated with a higher prevalence of intention to use PrEP [engaging in double penetration – adjusted prevalence ratio (aPR): 1.56, 95% CI: 1.44–1.69; being assigned female sex at birth – aPR: 1.34, 95% CI: 1.12–1.61; cruising – aPR: 1.21, 95% CI: 1.06–1.38; not using condoms – aPR: 1.20, 95% CI: 1.05–1.36; and being an immigrant – aPR: 1.16; 95% CI: 1.07–1.25], while having knowledge of postexposure prophylaxis (aPR: 0.91; 95% CI: 0.84–0.98), having a casual sexual partner (aPR: 0.86 and 0.85; 95% CI: 0.74–0.99 and 0.74–0.98), and engaging in group sex (aPR: 0.81; 95% CI: 0.73–0.90) were associated with a lower intention to use PrEP. Conclusion: The intention to use PrEP among MSM who engage in chemsex was high, and several factors were associated with this intention. Understanding the factors associated with the intention to use PrEP among MSM practicing chemsex is crucial for developing targeted interventions to increase PrEP uptake in this population. The results of this study suggest that tailored approaches are necessary to promote PrEP use in this population.
Two-Stage Revision ACL Reconstruction with Arthroscopic Tunnel Bone Grafting
Authors: Barnes Ryan H. , Kaeding Christopher C. , Magnussen Robert A. , Flanigan David C. 
Published: October 2023

Background: Anterior cruciate ligament (ACL) reconstruction is a common orthopedic surgery, and due to the increased number of primary reconstructions being performed, the number of revision ACL reconstructions is also increasing. Indications: Two-stage revision ACL reconstruction has lower failure rates compared to 1-stage and is indicated when significant tunnel expansion has occurred or malpositioned tunnels prohibit an adequate reconstruction. In this presentation, 2-stage revision ACL reconstruction was performed with an arthroscopic bone grafting technique of both the femoral and tibial tunnels secondary to tunnel osteolysis. Technique Description: Standard diagnostic arthroscopy is performed, and any chondral or meniscal pathology is addressed. The remnant ACL graft and all hardware are removed. The tunnels are debrided thoroughly. Using a modified syringe, the tunnels are packed with a mixture of cancellous bone chips and cortical fibers that have been hydrated with whole blood and platelet-rich plasma (PRP). The patient is placed into a brace postoperatively, and a computed tomography (CT) is obtained approximately 4 to 6 months postoperatively to assess for bone healing. Revision ACL reconstruction is performed once indicated with standard rehabilitation and return to play protocol. Results: Both 1-stage and 2-stage revision ACL reconstructions have been demonstrated to have significant improvement in outcomes scores preoperatively to postoperatively. However, 2-stage has lower failure rates compared to single-stage and has a high return to level of play. Discussion/Conclusion: Revision ACL reconstruction is becoming more commonly performed, and 2-stage revision is frequently required due to multiple factors. In this video, we demonstrate bone grafting for revision ACL reconstruction for tunnel osteolysis. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Differentiation of BCMA-specific induced pluripotent stem cells into rejuvenated CD8αβ+ T cells targeting multiple myeloma
Authors: Bae Jooeun , Kitayama Shuichi , Herbert Zach , Daheron Laurence , Kurata Keiji , Keskin Derin B. , Livak Kenneth , Li Shuqiang , Tarannum Mubin , Romee Rizwan , Samur Mehmet , Munshi Nikhil C. , Kaneko Shin , Ritz Jerome , Anderson Kenneth C. 
Published: October 2023

Abstract
A major hurdle in adoptive T-cell therapy is cell exhaustion and failure to maintain antitumor responses. Here, we introduce an induced pluripotent stem cell (iPSC) strategy for reprogramming and revitalizing precursor exhausted B-cell maturation antigen (BCMA)-specific T cells to effectively target multiple myeloma (MM). Heteroclitic BCMA72-80 (YLMFLLRKI)–specific CD8+ memory cytotoxic T lymphocytes (CTL) were epigenetically reprogrammed to a pluripotent state, developed into hematopoietic progenitor cells (CD34+ CD43+/CD14− CD235a−), differentiated into the T-cell lineage and evaluated for their polyfunctional activities against MM. The final T-cell products demonstrated (1) mature CD8αβ+ memory phenotype, (2) high expression of activation or costimulatory molecules (CD38, CD28, and 41BB), (3) no expression of immune checkpoint and senescence markers (CTLA4, PD1, LAG3, and TIM3; CD57), and (4) robust proliferation and polyfunctional immune responses to MM. The BCMA-specific iPSC–T cells possessed a single T-cell receptor clonotype with cognate BCMA peptide recognition and specificity for targeting MM. RNA sequencing analyses revealed distinct genome-wide shifts and a distinctive transcriptional profile in selected iPSC clones, which can develop CD8αβ+ memory T cells. This includes a repertoire of gene regulators promoting T-cell lineage development, memory CTL activation, and immune response regulation (LCK, IL7R, 4-1BB, TRAIL, GZMB, FOXF1, and ITGA1). This study highlights the potential application of iPSC technology to an adaptive T-cell therapy protocol and identifies specific transcriptional patterns that could serve as a biomarker for selection of suitable iPSC clones for the successful development of antigen-specific CD8αβ+ memory T cells to improve the outcome in patients with MM.
Acute myeloid leukemias with UBTF tandem duplications are sensitive to menin inhibitors
Authors: Barajas Juan M. , Rasouli Milad , Umeda Masayuki , Hiltenbrand Ryan , Abdelhamed Sherif , Mohnani Rebecca , Arthur Bright , Westover Tamara , Thomas Melvin E. , Ashtiani Minoo , Janke Laura J. , Xu Beisi , Chang Ti-Cheng , Rosikiewicz Wojciech , Xiong Emily , Rolle Chandra , Low Jonathan , Krishan Reethu , Song Guangchun , Walsh Michael P. , Ma Jing , Rubnitz Jeffrey E. , Iacobucci Ilaria , Chen Taosheng , Krippner-Heidenreich Anja , Zwaan Christian M. , Heidenreich Olaf , Klco Jeffery M. 
Published: October 2023

Abstract
UBTF tandem duplications (UBTF-TDs) have recently emerged as a recurrent alteration in pediatric and adult acute myeloid leukemia (AML). UBTF-TD leukemias are characterized by a poor response to conventional chemotherapy and a transcriptional signature that mirrors NUP98-rearranged and NPM1-mutant AMLs, including HOX-gene dysregulation. However, the mechanism by which UBTF-TD drives leukemogenesis remains unknown. In this study, we investigated the genomic occupancy of UBTF-TD in transformed cord blood CD34+ cells and patient-derived xenograft models. We found that UBTF-TD protein maintained genomic occupancy at ribosomal DNA loci while also occupying genomic targets commonly dysregulated in UBTF-TD myeloid malignancies, such as the HOXA/HOXB gene clusters and MEIS1. These data suggest that UBTF-TD is a gain-of-function alteration that results in mislocalization to genomic loci dysregulated in UBTF-TD leukemias. UBTF-TD also co-occupies key genomic loci with KMT2A and menin, which are known to be key partners involved in HOX-dysregulated leukemias. Using a protein degradation system, we showed that stemness, proliferation, and transcriptional signatures are dependent on sustained UBTF-TD localization to chromatin. Finally, we demonstrate that primary cells from UBTF-TD leukemias are sensitive to the menin inhibitor SNDX-5613, resulting in markedly reduced in vitro and in vivo tumor growth, myeloid differentiation, and abrogation of the UBTF-TD leukemic expression signature. These findings provide a viable therapeutic strategy for patients with this high-risk AML subtype.