bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Phase II Trial of Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance after Upfront Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: BMT CTN 1401
Authors: Chung David J. , Shah Nina , Wu Juan , Logan Brent , Bisharat Lina , Callander Natalie , Cheloni Giulia , Anderson Kenneth , Chodon Thinle , Dhakal Binod , Devine Steve , Somaiya Dutt Poorvi , Efebera Yvonne , Geller Nancy , Ghiasuddin Haider , Hematti Peiman , Holmberg Leona , Howard Alan , Johnson Bryon , Karagkouni Dimitra , Lazarus Hillard M. , Malek Ehsan , McCarthy Philip , McKenna David , Mendizabal Adam , Nooka Ajay , Munshi Nikhil , O'Donnell Lynn , Rapoport Aaron P. , Reese Jane , Rosenblatt Jacalyn , Soiffer Robert , Stroopinsky Dina , Uhl Lynne , Vlachos Ioannis S. , Waller Edmund K. , Young James W. , Pasquini Marcelo C. , Avigan David 
Published: July 2023

Abstract

Purpose:
Vaccination with dendritic cell (DC)/multiple myeloma (MM) fusions has been shown to induce the expansion of circulating multiple myeloma–reactive lymphocytes and consolidation of clinical response following autologous hematopoietic cell transplant (auto-HCT).

Patients and Methods:
In this randomized phase II trial (NCT02728102), we assessed the effect of DC/MM fusion vaccination, GM-CSF, and lenalidomide maintenance as compared with control arms of GM-CSF and lenalidomide or lenalidomide maintenance alone on clinical response rates and induction of multiple myeloma–specific immunity at 1-year posttransplant.

Results:
The study enrolled 203 patients, with 140 randomized posttransplantation. Vaccine production was successful in 63 of 68 patients. At 1 year, rates of CR were 52.9% (vaccine) and 50% (control; P = 0.37, 80% CI 44.5%, 61.3%, and 41.6%, 58.4%, respectively), and rates of VGPR or better were 85.3% (vaccine) and 77.8% (control; P = 0.2). Conversion to CR at 1 year was 34.8% (vaccine) and 27.3% (control; P = 0.4). Vaccination induced a statistically significant expansion of multiple myeloma–reactive T cells at 1 year compared with before vaccination (P = 0.024) and in contrast to the nonvaccine arm (P = 0.026). Single-cell transcriptomics revealed clonotypic expansion of activated CD8 cells and shared dominant clonotypes between patients at 1-year posttransplant.

Conclusions:
DC/MM fusion vaccination with lenalidomide did not result in a statistically significant increase in CR rates at 1 year posttransplant but was associated with a significant increase in circulating multiple myeloma–reactive lymphocytes indicative of tumor-specific immunity. Site-specific production of a personalized cell therapy with centralized product characterization was effectively accomplished in the context of a multicenter cooperative group study.
See related commentary by Qazilbash and Kwak, p. 4703
Women With Large Vessel Occlusion Acute Ischemic Stroke Are Less Likely to Be Routed to Comprehensive Stroke Centers
Authors: Tariq Muhammad Bilal , Ali Iman , Salazar‐Marioni Sergio , Iyyangar Ananya S. , Azeem Hussain M. , Khose Swapnil , Lopez Victor , Abdelkhaleq Rania , McCullough Louise D. , Sheth Sunil A. , Kim Youngran 
Published: July 2023

Background
Prehospital routing of patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) to centers capable of performing endovascular therapy may improve clinical outcomes. Here, we explore whether distance to comprehensive stroke centers (CSCs), stroke severity, and sex are associated with direct‐to‐CSC prehospital routing in patients with LVO AIS.

Methods and Results

In this cross‐sectional study, we identified consecutive patients with LVO AIS from a prospectively collected multihospital registry throughout the greater Houston area from January 2019 to June 2020. Primary outcome was prehospital routing to CSC and was compared between men and women using modified Poisson regression including age, sex, race or ethnicity, first in‐hospital National Institutes of Health Stroke Scale score, travel time, and distances to the closest primary stroke center and CSC. Among 503 patients with LVO AIS, 413 (82%) were routed to CSCs, and women comprised 46% of the study participants. Women with LVO AIS compared with men were older (73 versus 65,
P
<0.01) and presented with greater National Institutes of Health Stroke Scale score (14 versus 12,
P
=0.01). In modified Poisson regression, women were 9% less likely to be routed to CSCs compared with men (adjusted relative risk [aRR], 0.91 [0.84–0.99],
P
=0.024) and distance to nearest CSC ≤10 miles was associated with 38% increased chance of routing to CSC (aRR, 1.38 [1.26–1.52],
P
<0.001).

Conclusions
Despite presenting with more significant stroke syndromes and living within comparable distance to CSCs, women with LVO AIS were less likely to be routed to CSCs compared with men. Further study of the mechanisms behind this disparity is needed.
Biomechanical Analysis of Tibial Motion and ACL Graft Forces After ACLR With and Without LET at Varying Tibial Slopes
Authors: Pearce Stephanie L. , Bryniarski Anna R. , Brown Justin R. , Brady Alex W. , Gruskay Jordan A. , Dornan Grant J. , Vidal Armando F. , Godin Jonathan A. 
Published: July 2023

Background: Lateral extra-articular tenodesis (LET) is being performed more frequently with anterior cruciate ligament (ACL) reconstruction (ACLR) to decrease graft failure rates. The posterior tibial slope (PTS) affects ACL graft failure rates. The effect of ACLR + LET on tibial motion and graft forces with increasing PTS has not been elucidated. Hypothesis: LET would decrease anterior tibial translation (ATT), tibial rotation, and ACL graft force versus ACLR alone with increasing tibial slope throughout knee range of motion. Study Design: Controlled laboratory study. Methods: Twelve fresh-frozen cadaveric knees (mean donor age, 40.5 years; all female) were tested in 4 conditions (intact, ACL cut, ACLR, and ACLR + LET) with varying PTSs (5°, 10°, 15°, and 20°) at 3 flexion angles (0°, 30°, and 60°). Specimens were mounted to a load frame that applied a 500-N axial load with 1 N·m of internal rotation (IR) torque. The amount of tibial translation, IR, and graft force was measured. Results: Increasing PTS revealed a linear and significant increase in graft force at all flexion angles. LET reduced graft force by 8.3% (–5.8 N) compared with ACLR alone at 30° of flexion. At the same position, slope reduction resulted in reduced graft force by 17% to 22% (−12.3 to −15.2 N) per 5° of slope correction, with a 46% (−40.7 N) reduction seen from 20° to 5° of slope correction. For ATT, ACLR returned tibial translation to preinjury levels, as did ACLR + LET at all flexion angles, except full extension, where ACLR + LET reduced ATT by 2.5 mm compared with the intact state ( P = .019). Conclusion: Increased PTS was confirmed to increase graft forces linearly. Although ACLR + LET reduced graft force compared with ACLR alone, slope reduction had a larger effect across all testing conditions. No other clinically significant differences were noted between ACLR with versus without LET in regard to graft force, ATT, or IR. Clinical Relevance: Many authors have proposed LET in the setting of ACLR, revision surgery, hyperlaxity, high-grade pivot shift, and elevated PTS, but the indications remain unclear. The biomechanical performance of ACLR + LET at varying PTSs may affect daily practice and provide clarity on these indications.
Determinants of 1-Year Unfavorable Outcomes of Intravenous Alteplase Thrombolysis for Acute Ischemic Stroke
Authors: Zhai Mingfeng , Yang Jinwei , Cao Xiaoyan , Li Yingying , Xu Hui , Wang Yu 
Published: July 2023

Objective Intravenous thrombolytic therapy has become the standard of treatment for eligible patients with ischemic stroke. However, outcomes after receiving intravenous thrombolytic therapy vary widely. This study aims to investigate determinants of 1-year clinical outcomes of intravenous thrombolytic therapy for patients with acute ischemic stroke. Methods In a prospective, observational study, patients with acute ischemic stroke treated with intravenous thrombolysis were consecutively included, and clinical information and laboratory data were collected. The patients were followed up for 12 months after onset, and the 1-year clinical outcome was evaluated using modified Rankin Scale scores. A score ≥ 3 was defined as unfavorable functional outcome. Univariate and multivariate logistic regressions were used to assess the determinants of the 1-year clinical outcomes of intravenous thrombolysis for acute ischemic stroke. Results A total of 222 patients with intravenous thrombolysis were enrolled, and we identified 58 patients (26.1%) had unfavorable functional outcomes. Multivariate logistic regression analysis revealed that mean platelet volume-to-lymphocyte ratio (MPVLR) (odds ratio [OR] = 1.114, 95% confidence interval [CI]: 1.024–1.211, P = .012), atrial fibrillation (OR =  2.553, 95% CI: 1.086-6.002, P = .032), symptomatic stenosis occlusion (OR =  2.547, 95% CI: 1.269-5.110, P = .009), and baseline National Institutes of Health Stroke Scale (NIHSS) score (OR = 1.141, 95% CI: 1.074-1.212, P < .001) were independent predictors of unfavorable functional outcomes at 1 year. Conclusions In patients receiving intravenous thrombolysis, we found that MPVLR, atrial fibrillation, symptomatic stenosis occlusion, and baseline NIHSS score were significant predictors of unfavorable functional outcomes at 1 year.
Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis
Authors: Hu Yan , Chen Chen , Liang Zhengting , Liu Tao , Hu Xiaoling , Wang Guanying , Hu Jinxia , Xie Xiaolin , Liu Zhiyan 
Published: July 2023

Abstract
Background
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN.

Methods
Rats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected.

Results
CQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs.

Conclusions
CQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.
The landscape of PBMC methylome in canine mammary tumors reveals the epigenetic regulation of immune marker genes and its potential application in predicting tumor malignancy
Authors: Nam A-Reum , Heo Min , Lee Kang-Hoon , Kim Ji-Yoon , Won Sung-Ho , Cho Je-Yoel 
Published: July 2023

Abstract
Background
Genome-wide dysregulation of CpG methylation accompanies tumor progression and characteristic states of cancer cells, prompting a rationale for biomarker development. Understanding how the archetypic epigenetic modification determines systemic contributions of immune cell types is the key to further clinical benefits.

Results
In this study, we characterized the differential DNA methylome landscapes of peripheral blood mononuclear cells (PBMCs) from 76 canines using methylated CpG-binding domain sequencing (MBD-seq). Through gene set enrichment analysis, we discovered that genes involved in the growth and differentiation of T- and B-cells are highly methylated in tumor PBMCs. We also revealed the increased methylation at single CpG resolution and reversed expression in representative marker genes regulating immune cell proliferation (BACH2, SH2D1A, TXK, UHRF1). Furthermore, we utilized the PBMC methylome to effectively differentiate between benign and malignant tumors and the presence of mammary gland tumors through a machine-learning approach.

Conclusions
This research contributes to a better knowledge of the comprehensive epigenetic regulation of circulating immune cells responding to tumors and suggests a new framework for identifying benign and malignant cancers using genome-wide methylome.
Gene expression profile of the developing endosperm in durum wheat provides insight into starch biosynthesis
Authors: Chen Jiawen , Watson-Lazowski Alexander , Kamble Nitin Uttam , Vickers Martin , Seung David 
Published: July 2023

Abstract
Background
Durum wheat (Triticum turgidum subsp. durum) is widely grown for pasta production, and more recently, is gaining additional interest due to its resilience to warm, dry climates and its use as an experimental model for wheat research. Like in bread wheat, the starch and protein accumulated in the endosperm during grain development are the primary contributors to the calorific value of durum grains.

Results
To enable further research into endosperm development and storage reserve synthesis, we generated a high-quality transcriptomics dataset from developing endosperms of variety Kronos, to complement the extensive mutant resources available for this variety. Endosperms were dissected from grains harvested at eight timepoints during grain development (6 to 30 days post anthesis (dpa)), then RNA sequencing was used to profile the transcriptome at each stage. The largest changes in gene expression profile were observed between the earlier timepoints, prior to 15 dpa. We detected a total of 29,925 genes that were significantly differentially expressed between at least two timepoints, and clustering analysis revealed nine distinct expression patterns. We demonstrate the potential of our dataset to provide new insights into key processes that occur during endosperm development, using starch metabolism as an example.

Conclusion
We provide a valuable resource for studying endosperm development in this increasingly important crop species.
Immediate and long-term changes in infectious diseases in China at the “First-level-response”, “Normalized-control” and “Dynamic-COVID-zero” stages from 2020 to 2022: a multistage interrupted-time-series-analysis
Authors: Shi Tianshan , Zhang Xiaoshu , Meng Lei , Li Donghua , Jin Na , Zhao Xin , Zheng Hongmiao , Wang Tingrong , Li Rui , Ren Xiaowei 
Published: July 2023

Abstract
Background
From January 2020 to December 2022, China implemented “First-level-response”, “Normalized-control” and “Dynamic-COVID-zero” to block the COVID-19 epidemic; however, the immediate and long-term impact of three strategies on other infectious diseases and the difference in their impact is currently unknown. We aim to provide a more comprehensive understanding of the impact of non-pharmacological interventions (NPIs) on infectious diseases in China.

Methods
We collected data on the monthly case count of infectious diseases in China from January 2015 to July 2022. After considering long-term trends using the Cox-Stuart test, we performed the two ratio Z tests to preliminary analyze the impact of three strategies on infectious diseases. Next, we used a multistage interrupted-time-series analysis fitted by the Poisson regression to evaluate and compare the immediate and long-term impact of three strategies on infectious diseases in China.

Results
Compared to before COVID-19, the incidence of almost all infectious diseases decreased immediately at stages 1, 2, and 3; meanwhile, the slope in the incidence of many infectious diseases also decreased at the three stages. However, the slope in the incidence of all sexually transmitted diseases increased at stage 1, the slope in the incidence of all gastrointestinal infectious diseases increased at stage 2, and the slope in the incidence of some diseases such as pertussis, influenza, and brucellosis increased at stage 3. The immediate and long-term limiting effects of “Normalized-control” on respiratory-transmitted diseases were weaker than “First-level-response” and the long-term limiting effects of “Dynamic-COVID-zero” on pertussis, influenza, and hydatid disease were weaker than “Normalized-control”.

Conclusions
Three COVID-19 control strategies in China have immediate and long-term limiting effects on many infectious diseases, but there are differences in their limiting effects. Evidence from this study shows that pertussis, influenza, brucellosis, and hydatid disease began to recover at stage 3, and relaxation of NPIs may lead to the resurgence of respiratory-transmitted diseases and vector-borne diseases.
Causal association between body mass index and temporomandibular disorders: a bidirectional two-sample Mendelian randomization analysis
Authors: Chen Xin , Cheng Zheng , Xu Junyu , Zhao Zhibai , Jiang Qianglin 
Published: July 2023

AbstractBackgroundObservational studies have shown that body mass index (BMI) is highly correlated with the occurrence of temporomandibular disorders (TMDs). However, these studies failed to present a causal relationship. Thus, we aimed to performed a Mendelian randomization (MR) study to investigate causality between BMI and TMDs.MethodsWe performed a two-sample bidirectional MR analysis using large-scale genome-wide association studies (GWAS). Data were obtained from a large-scale BMI dataset (N = 322,154), TMDs dataset (N = 134,280). The causal effects were estimated with inverse-variance weighted (IVW) method, MR Egger, weighted median. Sensitivity analyses were implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot.ResultsIn the forward MR analysis, a genetic prediction of low BMI was causally associated with a higher risk of TMDs (IVW OR: 0.575, 95% CI: 0.415–0.798,p: 0.001). Similar results were obtained using other complementary methods (MR Egger OR: 0.270, 95% CI: 0.104–0.698,p: 0.009; weighted median OR: 0.496, 95% CI: 0.298–0.826,p: 0.007). In the reverse MR results, TMDs was shown to have no significant effect on BMI (allp > 0.05). No pleiotropy and heterogeneity were detected in the bidirectional analysis (p > 0.05).ConclusionA lower BMI might be causally associated with increased risk of TMDs, supporting the importance of weight control for the prevention of TMDs. Clinicians should pay more attention to the low-BMI patients among those seeking medical advice due to temporomandibular joint discomfort.
Male pseudohermaphroditism in a complex malformed calf born with an acardius amorphus cotwin—a case report
Authors: Kusaka Hiromi , Sugiyama Makoto , Kameshima Satoshi , Kakizaki Takehiko , Suzuki Yasunori , Ando Ryo , Miura Hiroshi , Kikuchi Motohiro , Kawaguchi Hiroaki , Sakaguchi Minoru 
Published: July 2023

Abstract
Background
Male pseudohermaphroditism is a developmental anomaly wherein animals are genetically and gonadally male, but their internal and/or external genitalia resemble those of females. In cattle, pseudohermaphroditism is often accompanied by multiple severe malformations. To the best of our knowledge, this is the first report of male pseudohermaphroditism in a complex malformed calf born with an acardius amorphous cotwin.

Case presentation
This report describes the case of a three-day-old, male anurous Japanese Black calf born with an acardius amorphous cotwin, complete absence of the tail, agenesis of the anus, separate scrota, and umbilical hernia. Transthoracic echocardiography and computed tomography revealed serious malformations in the skeletal system and the circulatory, digestive, urinary, and genital organs. Necropsy revealed rectal atresia, immature testes, epididymis, and penis, but no male accessory gonads. Histological analyses revealed vaginal- and uterine-like tissues adjacent to or fused to the rectum. Fluorescence in situ hybridization detected X and Y chromosomes, and some cells presented two X-probe signals in the same nucleus.

Conclusions
In contrast to the male genitalia, the female genitalia derived from the Müllerian ducts were difficult to detect by necropsy in the presented case. Many similar cases may be overlooked in clinical practice.
Exploring the role and mechanism of Fuzi decoction in the treatment of osteoporosis by integrating network pharmacology and experimental verification
Authors: Li Fudong , Guo Chuan , Zhang Shikai , Zheng Bing , Sun Kaiqiang , Shi Jiangang 
Published: July 2023

Abstract
Background
Fuzi decoction (FZD), a traditional Chinese medicine formula, was used to treat musculoskeletal diseases by warming channels, strengthening yang and dispelling pathogenic cold and dampness. In clinical practice, FZD has been used to treat rheumatoid arthritis and osteoarthritis. It alleviated osteoarticular disorders through ameliorating the degradation of cartilage and improving meniscal damage in osteoarthritis, while its roles and mechanisms in the treatment of bone loss diseases remain unclear. This study aims to investigate the underlying mechanisms of FZD in treating osteoporosis using an integrative method of network pharmacology and experimental study.

Methods
In this study, network pharmacology was used to predict the core targets and potential pathways of the bioactive ingredients of FZD to attenuate osteoporosis. Molecular docking was performed to evaluate the interactions between core compounds and key targets. In addition, both cell and animal experiments were carried out to validate the role and potential mechanism in treating osteoporosis.

Results
In the present study, data revealed that kaempferol, beta-sitosterol, stigmasterol, fumarine, and (+)-catechin may be the primary bioactive ingredients of FZD in the treatment of osteoporosis, which were closely associated with the osteoporosis-related targets. And the KEGG results indicated that the NF-κB pathway was closely associated with the function of FZD in treating osteoporosis. In addition, in vivo demonstrated that FZD ameliorated osteoporosis. In vitro experiments showed that the pro-apoptotic factors indicators including CASP3 and BAX were decreased by FZD and the anti-apoptotic factor BCL2 was increased by FZD. In addition, FZD significantly suppressed the osteoclast differentiation in culture and the expression levels of osteoclast-related genes including TRAF6, CTSK, and MMP9. And the NF-κB pathway was confirmed, via in vitro experiment, to be involved in osteoclast differentiation.

Conclusions
This study demonstrated that FZD played a pivotal role in suppressing the osteoclast differentiation via regulating the NF-κB pathway, indicating that FZD could be a promising antiosteoporosis drug and deserve further investigation.