bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in diagnosis and treatment of bladder cancer
Authors: Lopez-Beltran Antonio , Cookson Michael S , Guercio Brendan J , Cheng Liang 
Published: February 2024

Abstract
Bladder cancer remains a leading cause of cancer death worldwide and is associated with substantial impacts on patient quality of life, morbidity, mortality, and cost to the healthcare system. Gross hematuria frequently precedes the diagnosis of bladder cancer. Non-muscle-invasive bladder cancer (NMIBC) is managed initially with transurethral resection of a bladder tumor (TURBT), followed by a risk stratified approach to adjuvant intravesical therapy (IVe), and is associated with an overall survival of 90%. However, cure rates remain lower for muscle invasive bladder cancer (MIBC) owing to a variety of factors. NMIBC and MIBC groupings are heterogeneous and have unique pathological and molecular characteristics. Indeed, The Cancer Genome Atlas project identified genetic drivers and luminal and basal molecular subtypes of MIBC with distinct treatment responses. For NMIBC, IVe immunotherapy (primarily BCG) is the gold standard treatment for high grade and high risk NMIBC to reduce or prevent both recurrence and progression after initial TURBT; novel trials incorporate immune checkpoint inhibitors. IVe gene therapy and combination IVe chemotherapy have recently been completed, with promising results. For localized MIBC, essential goals are improving care and reducing morbidity following cystectomy or bladder preserving strategies. In metastatic disease, advances in understanding of the genomic landscape and tumor microenvironment have led to the implementation of immune checkpoint inhibitors, targeted treatments, and antibody-drug conjugates. Defining better selection criteria to identify the patients most likely to benefit from a specific treatment is an urgent need.
Association between macro- and microvascular damage and sarcopenia index in individuals with type 2 diabetes mellitus
Authors: Xu Hui , Xiang Qun-Yan , Zhan Jun-Kun , Wang Yi , Wang Yan-Jiao , Li Shuang , Liu You-Shuo 
Published: February 2024

Sarcopenia was recently reported to be relevant to an increased macro-and microvascular disease risk. Sarcopenia index (SI) has been identified as a surrogate marker for sarcopenia. The aim of the present study was to investigate the association between macro- and microvascular disease and SI in patients with type 2 diabetes mellitus (T2DM). A total of 783 patients with T2DM were enrolled in this cross-sectional study. The SI was calculated by (serum creatinine [mg/dL]/cystatin C [mg/L]) × 100. The subjects were divided into three groups according to SI tertiles: T1 (41.27–81.37), T2 (81.38– 99.55), and T3 (99.56–192.31). Parameters of macro- and microvascular complications, including diabetic retinopathy (DR), micro- and macroalbuminuria (MAU), diabetic peripheral neuropathy (DPN), and lower extremity peripheral artery disease (LEAD) were evaluated. Multivariate logistic regression analysis revealed that when taking the top tertile of SI as a reference, an increasing trend of the prevalence of DR, MAU, DPN, and LEAD were presented (all P for trend < 0.05), where the OR (95% CI) for DR prevalence was 1.967 (1.252–3.090) in T2, 2.195 (1.278–3.769) in T1, for MAU was 1.805 (1.149–2.837) in T2, 2.537 (1.490–4.320) in T1, for DPN was 2.244 (1.485–3.391) in T2, 3.172 (1.884–5.341) in T1, and for LEAD was 2.017 (1.002–4.057) in T2, 2.405 (1.107–5.225) in T1 (all P < 0.05). Patients with lower SI were more inclined to have an increased risk of macro- and microvascular damage in T2DM population, which may be related to sarcopenia.
Evaluation of the effects of hempseed cake on plasma metabolites and cytokines in response to an LPS challenge in finishing steers
Authors: Winders Thomas M. , Amat Samat , Swanson Kendall C. 
Published: February 2024

A lipopolysaccharide (LPS; 0.25 µg LPS/kg of body weight (BW)) challenge in steers ( n = 5; initial BW = 542 kg, SD = 40 kg; Youden square) was conducted to evaluate feeding 0% (dry matter basis; control) or 20% hempseed cake (HEMP) or corn distillers grains (DDGS) on plasma metabolites and cytokines. Plasma isoleucine, leucine, tryptophan, aspartic acid, glycine, tyrosine, total nonessential amino acids, interleukin-1α (IL-1α), interleukin-36 receptor antagonist (IL-36RA), and tumor necrosis factor-α (TNF-α) decreased ( P ≤ 0.04) in steers fed hempseed cake compared to steers fed DDGS after the LPS challenge. These data suggest that hempseed cake may influence inflammation by altering cytokine production and by increasing degradation and/or utilization of some amino acids.
Evaluation of a baseline for the study of azimuthal correlations of charmed mesons in heavy-ion collisions using PYTHIA 8 and Herwig++ models
Authors: Gwiździel Katarzyna , Kikoła Daniel , Trzeciak Barbara 
Published: February 2024

AbstractMeasurements of azimuthal correlations of charmed mesons in high-energy heavy-ion collisions can shed light on transport properties of the Quark-Gluon Plasma. The STAR experiment collected in 2014 and 2016 a large sample of Au+Au reactions at $$\sqrt{s_{NN}}$$

s

NN

= 200 GeV, making such a study possible. However, such a measurement in p+p collisions at the same energy is not feasible so far. To provide such a baseline, we report a model study of the azimuthal correlations between charmed mesons in p+p collisions at $$\sqrt{s}$$

s

= 200 GeV, 500 GeV and 1.96 TeV. We used two Monte Carlo generators, PYTHIA 8 and Herwig++. We compare their predictions and validate them against available data from the STAR and CDF experiments to provide a reliable p+p baseline for the correlation studies in heavy-ion collisions at experiments at RHIC. We also discuss prospects for such measurements.
Unveiling SU(3) flux tubes at nonzero temperature: electric fields and magnetic currents
Authors: Baker M. , Chelnokov V. , Cosmai L. , Cuteri F. , Papa A. 
Published: February 2024

AbstractWe report on the results of measuring the chromoelectric fields in a flux tube created by a static quark-antiquark pair in finite-temperature SU(3) gauge theory. Below the deconfinement temperature the field behavior is similar to the zero-temperature case. Above the deconfinement temperature the field shape remains the same, but the field values drop when the distance between the quark and antiquark increases, thus showing the disappearance of the confining potential.
Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M. 
Published: February 2024

Abstract

Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into emergent aggressive variant prostate cancer (AVPC), which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflect and retain key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. We compared 15 NE versus 33 AdCa samples, which included six different PDX tumors for each group in biological replicates, and identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of concordance from PDX tumor-matched protein and mRNA revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa.

Implications:
Overall, our study highlights the importance of protein-based identification when compared with RNA and provides a rich resource of new and feasible targets for clinical assay development and in understanding the underlying biology of these tumors.
Intragenic Rearrangement Burden Associates with Immune Cell Infiltration and Response to Immune Checkpoint Blockade in Cancer
Authors: Zhang Han , Lee Sanghoon , Muthakana Renee R. , Lu Binfeng , Boone David N. , Lee Daniel , Wang Xiao-Song 
Published: February 2024

Abstract
Immune checkpoint blockade (ICB) can induce durable cancer remission. However, only a small subset of patients gains benefits. While tumor mutation burden (TMB) differentiates responders from nonresponders in some cases, it is a weak predictor in tumor types with low mutation rates. Thus, there is an unmet need to discover a new class of genetic aberrations that predict ICB responses in these tumor types. Here, we report analyses of pan-cancer whole genomes which revealed that intragenic rearrangement (IGR) burden is significantly associated with immune infiltration in breast, ovarian, esophageal, and endometrial cancers, particularly with increased M1 macrophage and CD8+ T-cell signatures. Multivariate regression against spatially counted tumor-infiltrating lymphocytes in breast, endometrial, and ovarian cancers suggested that IGR burden is a more influential covariate than other genetic aberrations in these cancers. In the MEDI4736 trial evaluating durvalumab in esophageal adenocarcinoma, IGR burden correlated with patient benefits. In the IMVigor210 trial evaluating atezolizumab in urothelial carcinoma, IGR burden increased with platinum exposure and predicted patient benefit among TMB-low, platinum-exposed tumors. Altogether, we have demonstrated that IGR burden correlates with T-cell inflammation and predicts ICB benefit in TMB-low, IGR-dominant tumors, and in platinum-exposed tumors.
High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models
Authors: Degagné Émilie , Donohoue Paul D. , Roy Suparna , Scherer Jessica , Fowler Tristan W. , Davis Ryan T. , Reyes Gustavo A. , Kwong George , Stanaway Morena , Larroca Vicena Vanina , Mutha Devin , Guo Raymond , Edwards Leslie , Schilling Benjamin , Shaw McKay , Smith Stephen C. , Kohrs Bryan , Kufeldt Heinrich J. , Churchward Glen , Ruan Finey , Nyer David B. , McSweeney Kyle , Irby Matthew J. , Fuller Christopher K. , Banh Lynda , Toh Mckenzi S. , Thompson Matthew , Owen Arthur L.G. , An Zili , Gradia Scott , Skoble Justin , Bryan Mara , Garner Elizabeth , Kanner Steven B. 
Published: February 2024

Abstract
Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include prevention of graft-vs-host disease (GvHD) and suppression of allograft rejection. Here, we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma. CB-011 is a hypoimmunogenic, allogeneic anti–B-cell maturation antigen (BCMA) CAR T cell therapy candidate. CB-011 cells feature 4 genomic alterations and were engineered from healthy donor–derived T cells using a Cas12a CRISPR hybrid RNA–DNA (chRDNA) genome-editing technology platform. To address allograft rejection, CAR T cells were engineered to prevent endogenous HLA class I complex expression and overexpress a single-chain polyprotein complex composed of beta-2 microglobulin (B2M) tethered to HLA-E. In addition, T-cell receptor (TCR) expression was disrupted at the TCR alpha constant locus in combination with the site-specific insertion of a humanized BCMA-specific CAR. CB-011 cells exhibited robust plasmablast cytotoxicity in vitro in a mixed lymphocyte reaction in cell cocultures derived from patients with multiple myeloma. In addition, CB-011 cells demonstrated suppressed recognition by and cytotoxicity from HLA-mismatched T cells. CB-011 cells were protected from natural killer cell–mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M–HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma.
See related Spotlight by Caimi and Melenhorst, p. 385
Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation
Authors: Maizels Leonid , Heller Eyal , Landesberg Michal , Glatstein Shany , Huber Irit , Arbel Gil , Gepstein Amira , Aronson Doron , Sharabi Shirley , Beinart Roy , Segev Amit , Maor Elad , Gepstein Lior 
Published: February 2024

BACKGROUND:
Electroporation is a promising nonthermal ablation method for cardiac arrhythmia treatment. Although initial clinical studies found electroporation pulsed-field ablation (PFA) both safe and efficacious, there are significant knowledge gaps concerning the mechanistic nature and electrophysiological consequences of cardiomyocyte electroporation, contributed by the paucity of suitable human in vitro models. Here, we aimed to establish and characterize a functional in vitro model based on human-induced pluripotent stem cells (hiPSCs)-derived cardiac tissue, and to study the fundamentals of cardiac PFA.

METHODS:
hiPSC-derived cardiomyocytes were seeded as circular cell sheets and subjected to different PFA protocols. Detailed optical mapping, cellular, and molecular characterizations were performed to study PFA mechanisms and electrophysiological outcomes.

RESULTS:

PFA generated electrically silenced lesions within the hiPSC-derived cardiac circular cell sheets, resulting in areas of conduction block. Both reversible and irreversible electroporation components were identified. Significant electroporation reversibility was documented within 5 to 15-minutes post-PFA. Irreversibly electroporated regions persisted at 24-hours post-PFA. Per single pulse, high-frequency PFA was less efficacious than standard (monophasic) PFA, whereas increasing pulse-number augmented lesion size and diminished reversible electroporation. PFA augmentation could also be achieved by increasing extracellular Ca
2+
levels. Flow-cytometry experiments revealed that regulated cell death played an important role following PFA. Assessing for PFA antiarrhythmic properties, sustainable lines of conduction block could be generated using PFA, which could either terminate or isolate arrhythmic activity in the hiPSC-derived cardiac circular cell sheets.

CONCLUSIONS:
Cardiac electroporation may be studied using hiPSC-derived cardiac tissue, providing novel insights into PFA temporal and electrophysiological characteristics, facilitating electroporation protocol optimization, screening for potential PFA-sensitizers, and investigating the mechanistic nature of PFA antiarrhythmic properties.
The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft
Authors: Li Xiao , Turaga Diwakar , Li Rich G. , Tsai Chang-Ru , Quinn Julianna N. , Zhao Yi , Wilson Ruby , Carlson Katherine , Wang Jun , Spinner Joseph A. , Hickey Edward J. , Adachi Iki , Martin James F. 
Published: February 2024

BACKGROUND:
Much of our knowledge of organ rejection after transplantation is derived from rodent models.

METHODS:
We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data.

RESULTS:
Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell signatures similar to donor-derived resident macrophages; however, they lack signatures of pro-reparative phagocytic activity typical of donor-derived resident macrophages and instead express profibrotic genes. In contrast, recipient MP1s express genes consistent with hallmarks of cellular rejection. Our data suggest that recipient MP1s activate a subset of natural killer cells, turning them into a cytotoxic cell population through feed-forward signaling between recipient MP1s and natural killer cells.

CONCLUSIONS:
Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure.
A Brief Guide to Establishing Phylogenetically Defined Names under the International Code of Phylogenetic Nomenclature (PhyloCode)
Authors: Cantino Philip D. , De Queiroz Kevin , Cellinese Nico 
Published: February 2024

To facilitate preparation of nomenclatural treatments that follow the PhyloCode, we provide here an outline of the requirements in the form of a checklist. Rules are categorized as pertaining to publication requirements, protologue content, the defined clade name, or the phylogenetic definition. Two sample protologues are included to illustrate the elements that need to be included to establish a name under the PhyloCode. In addition, we provide detailed instructions for registering a name in RegNum, as required by the PhyloCode.
Health service and medication costs associated with common mental disorders and subthreshold symptoms in women: Findings from the Geelong Osteoporosis Study in Australia
Authors: Chatterton Mary Lou , Faller Jan , Le Long Khanh-Dao , Engel Lidia , Williams Lana J , Pasco Julie A , Mihalopoulos Cathy 
Published: February 2024

Objective: This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women. Methods: Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups. Results: Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p < .05) compared to no common mental disorder. Conclusions: Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers.
Development and Testing of the School Healthcare Partnership Scale for Parents
Authors: Uhm Ju-Yeon , Kim Suhee 
Published: February 2024

Background: Cooperation between parents and school nurses is essential for the successful completion of school courses and a healthy school life for children with long-term conditions. Therefore, this study aimed to develop and test a scale to measure parental perceptions of partnerships between school nurses and parents in the school health care (SHC) system for children with type 1 diabetes (T1D). Methods: The content validity, factorial structure validity, convergent validity, discriminant validity, known-group validity, internal consistency reliability, and test-retest reliability of the School Healthcare Partnership Scale for Parents (SHCPS-P) were evaluated. Data were analyzed by performing exploratory factor analysis (EFA), Pearson’s correlation, Cronbach’s α, and independent t-tests. The total sample included 155 parents for the EFA and 49 parents for the stability test. Seventeen items, grouped into 3 dimensions, were extracted through principal axis factoring. Results: The total variance explained by these factors was 53.57%. The scale demonstrated a high correlation with parental satisfaction regarding school nursing and a moderate correlation with diabetes-related safety, thereby showing convergent validity. A low correlation with empathy demonstrated discriminant validity. A significant difference existed in the partnership scores in known-group comparisons. Cronbach’s α was 0.95, and the test-retest correlation coefficient was 0.95, which showed reliability. Conclusions: This study suggests that the SHCPS-P is a reliable and valid tool for measuring the perception of SHC partnership among parents of children with T1D and can be used as an indicator to measure parents’ perspectives about SHC.
The clinical and economic impact of chronic venous insufficiency-associated lymphedema and the prevalence of persistent edema after venous intervention
Authors: Genet Matthew , Labropoulos Nicos , Gasparis Antonios , O’Donnell Thomas , Desai Kush 
Published: February 2024

Objectives To determine the demographics, outcomes, and healthcare utilization of patients with chronic venous insufficiency-associated lymphedema (CVI-LED) and the prevalence of lymphedema-specific therapy use after venous intervention. Methods The IBM MarketScan Commercial and Medicare Claims Databases were examined for patients with CVI-LED. Patient demographics and the use of lymphedema-specific therapy before and after venous intervention were collected. Results Of 85,601 LED patients identified, 8,406 also had a diagnosis of CVI. In the CVI-LED group, 1051 underwent endovenous ablation or venous stent placement. The use of lymphedema-specific therapy before and after venous intervention was 52% and 39%, respectively ( p < .05). The mean time of initiation of LED-specific therapy following venous intervention was 265 days after ablation and 347 days after stent placement. Conclusion Treating venous hypertension improves certain venous-related signs and symptoms of CVI. However, a significant proportion of patients have persistent edema which may reflect underlying, sub-optimally treated LED.