bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative analysis of the impact of respiratory state on the heartbeat-induced movements of the heart and its substructures
Authors: Liang Benzhe , Gong Guanzhong , Tong Ying , Wang Lizhen , Su Ya , Wang Huadong , Li Zhenkai , Yan Hongyu , Zhang Xiaohong , Yin Yong 
Published: February 2024

Abstract
Purpose
This study seeks to examine the influence of the heartbeat on the position, volume, and shape of the heart and its substructures during various breathing states. The findings of this study will serve as a valuable reference for dose-volume evaluation of the heart and its substructures in radiotherapy for treating thoracic tumors.

Methods
Twenty-three healthy volunteers were enrolled in this study, and cine four-dimensional magnetic resonance images were acquired during periods of end-inspiration breath holding (EIBH), end-expiration breath holding (EEBH), and deep end-inspiration breath holding (DIBH). The MR images were used to delineate the heart and its substructures, including the heart, pericardium, left ventricle (LV), left ventricular myocardium, right ventricle (RV), right ventricular myocardium (RVM), ventricular septum (VS), atrial septum (AS), proximal and middle portions of the left anterior descending branch (pmLAD), and proximal portion of the left circumflex coronary branch (pLCX). The changes in each structure with heartbeat were compared among different respiratory states.

Results
Compared with EIBH, EEBH increased the volume of the heart and its substructures by 0.25–3.66%, while the average Dice similarity coefficient (DSC) increased by − 0.25 to 8.7%; however, the differences were not statistically significant. Conversely, the VS decreased by 0.89 mm in the left–right (LR) direction, and the displacement of the RV in the anterior–posterior (AP) direction significantly decreased by 0.76 mm (p < 0.05). Compared with EIBH and EEBH, the average volume of the heart and its substructures decreased by 3.08–17.57% and 4.09–20.43%, respectively, during DIBH. Accordingly, statistically significant differences (p < 0.05) were observed in the volume of the heart, pericardium, LV, RV, RVM, and AS. The average DSC increased by 0–37.04% and − 2.6 to 32.14%, respectively, with statistically significant differences (p < 0.05) found in the right ventricular myocardium and interatrial septum. Furthermore, the displacements under DIBH decreased in the three directions (i.e.,− 1.73 to 3.47 mm and − 0.36 to 2.51 mm). In this regard, the AP displacement of the heart, LV, RV, RVM, LR direction, LV, RV, and AS showed statistically significant differences (p < 0.05). The Hausdorff distance (HD) of the heart and its substructures under the three breathing states are all greater than 11 mm.

Conclusion
The variations in the displacement and shape alterations of the heart and its substructures during cardiac motion under various respiratory states are significant. When assessing the dose-volume index of the heart and its substructures during radiotherapy for thoracic tumors, it is essential to account for the combined impacts of cardiac motion and respiration.
Clinical effect of the internal fixation for rib fracture with single utility port complete video-assisted thoracoscopic surgery
Authors: Wang Jindong , Sun Zhiguang , Liu Yongshuai , Gong Weiyong , Wang Jianxin , Deng Junyi , Fu Yue , Lan Jishan 
Published: February 2024

AbstractBackgroundsThe internal fixation for rib fracture with single-operation-port (two ports) complete video-assisted thoracoscopic surgery (VATS) is a promising surgical approach for treating multiple rib fractures. The study aimed to investigate the minimally invasive surgical procedure’s clinical effect in treating multiple rib fractures.MethodsSeventy-three patients with multiple rib fractures were divided into two groups according to surgical procedure. In the study group, 42 patients were operated on with the internal fixation of rib fracture with single-operation-port complete VATS. In the control group, this study performed the open operative internal fixation for rib fracture with traditional thoracotomy on 31 patients. The surgical-related indexes were retrospectively analyzed. These included the operative time, the intraoperative blood loss, the drainage amount of the chest tube, the placement time of the chest tube, the postoperative hospital stay, the incidence of postoperative complications, the imaging efficacy of rib fixation of rib fractures, and visual analog scale of pain scoring (VAS scoring).ResultsThere was no difference in the operative time between the study and control groups (P = 0.806). The intraoperative blood loss, the chest tube drainage amount, the chest tube placement time, the postoperative hospital stay, and the incidence of postoperative complications in the study group were lower than those in the control group (P < 0.05). There was no significant difference in the imaging efficacy of rib fixation of rib fractures between the two groups (P = 0.806). VAS scores in the study group on the seventh postoperative day were significantly reduced compared with the control group (P = 0.026).ConclusionThe internal fixation for rib fractures with single-operation-port complete VATS is a feasible, safe, simple, and minimally invasive surgical procedure to treat multiple rib fractures, which is worthy of clinical application.
Nrf2/HO-1 signaling activation alleviates cigarette smoke-induced inflammation in chronic obstructive pulmonary disease by suppressing NLRP3-mediated pyroptosis
Authors: Zhang Yanan , Wang Jinxia , Wang Yuling , Lei Kai 
Published: February 2024

Abstract
Background
This study examined the effect of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway on chronic obstructive pulmonary disease (COPD) and the potential molecular mechanism.

Methods
A COPD mouse model was established by cigarette smoke exposure and administered with either ML385 or dimethyl fumarate (DMF). Airway resistance of mice was detected. IL-1β and IL-6 levels in mice alveolar lavage fluid were examined by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining and immunohistochemical of lung tissues were utilized to detect lung injury and NLRP3 expression. DMF was used to treat COPD cell model constructed by exposing normal human bronchial epithelial (NHBE) cells to cigarette smoke extract. NHBE cells were transfected by NLRP3-expression vectors. Expression of proteins was detected by Western blot.

Results
COPD mice showed the enhanced airway resistance, the inactivated Nrf2/HO-1 pathway and the overexpressed NLRP3, Caspase-1 and GSDMD-N proteins in lung tissues, and the increased IL-1β and IL-6 levels in alveolar lavage fluid. ML385 treatment augmented these indicators and lung injury in COPD mice. However, DMF intervention attenuated these indicators and lung injury in COPD mice. Nrf2/HO-1 pathway inactivation and overexpression of NLRP3, Caspase-1 and GSDMD-N proteins were observed in COPD cells. DMF intervention activated Nrf2/HO-1 pathway and down-regulated NLRP3, Caspase-1 and GSDMD-N proteins in COPD cells. However, NLRP3 overexpression abolished the effect of DMF on COPD cells.

Conclusion
Nrf2/HO-1 pathway activation may alleviate inflammation in COPD by suppressing the NLRP3-related pyroptosis. Activating the Nrf2/HO-1 pathway may be an effective method to treat COPD.
Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice
Authors: Yamamoto Naoki , Yokose Jun , Ramesh Kritika , Kitamura Takashi , Ogawa Sachie K. 
Published: February 2024

AbstractEntorhinal cortical (EC)-hippocampal (HPC) circuits are crucial for learning and memory. Although it was traditionally believed that superficial layers (II/III) of the EC mainly project to the HPC and deep layers (V/VI) receive input from the HPC, recent studies have highlighted the significant projections from layers Va and VI of the EC into the HPC. However, it still remains unknown whether Vb neurons in the EC provide projections to the hippocampus. In this study, using a molecular marker for Vb and retrograde tracers, we identified that the outer layer of Vb neurons in the medial EC (MEC) directly project to both dorsal and ventral hippocampal dentate gyrus (DG), with a significant preference for the ventral DG. In contrast to the distribution of DG-projecting Vb cells, anterior thalamus-projecting Vb cells are distributed through the outer to the inner layer of Vb. Furthermore, dual tracer injections revealed that DG-projecting Vb cells and anterior thalamus-projecting Vb cells are distinct populations. These results suggest that the roles of MEC Vb neurons are not merely limited to the formation of EC-HPC loop circuits, but rather contribute to multiple neural processes for learning and memory.
Clinical characteristics and outcomes of patients with TSH-secreting pituitary adenoma and Graves’ disease - a case report and systematic review
Authors: Khan Adeel Ahmad , Ibrahim Shahd I. , Ata Fateen , Wazwaz Bara , Hanoun Mohammad Abdulalim , Belkhair Sirajeddin , Rohani Zaina Seros , Dabbous Zeinab 
Published: February 2024

Abstract
Background
Coexistence of TSH-secreting pituitary adenoma (TSHoma) and Graves’ disease (GD) is rare and complicates the management decision.

Methods
We present a case of the co-existence of TSHoma and GD. In addition, we systematically searched articles describing TSHoma and GD in the same patient published until 20th March 2023, using Pubmed, Scopus and Embase.

Case presentation
A 46-year-old man presented with symptoms of thyrotoxicosis. His thyroid function tests showed serum TSH 3.35 (reference range 0.3–4.2) mIU/L, FT3 19.7 (3.7–6.4) pmol/L, and FT4 68.9 (11-23.3) pmol/L. The serum TSH receptor antibody was 11.5 mIU/L (positive at ≥ 1.75 mIU/L). Pituitary magnetic resonance imaging showed macroadenoma compressing the optic chiasm. The patient underwent trans-sphenoidal resection of pituitary adenoma. Postoperatively, he remained on maintenance carbimazole and octreotide.

Results
Fourteen articles comprising 15 patients were identified from the systemic search. A total of 16 patients (including the current case) were included in the systematic review. The mean (± SD) age at diagnosis was 41 ± 13.6 years. The majority were females (75%). The median (IQR) TSH was 1.95 (0.12–5.5) mIU/L, the median (IQR) free T3 was 11.7 (7.6–19.7) pmol/L and the median (IQR) free T4 level was 47.6 (33.3–64.4) pmol/L. Ten (76.9%) patients had positive TSH receptor antibody levels. 84.6% had pituitary macroadenoma. Pituitary surgery was performed in 12 (75%) patients. At the last follow-up, 4 (25%) patients had complete resolution of symptoms after pituitary surgery, 3 (18.7%) were on maintenance treatment with thionamides for GD, 1 (6.25%) on beta-blockers and 1 (6.25%) on somatostatin analog.

Conclusion
TSHoma and GD can co-exist, and it is essential to identify this rare association as it can significantly impact treatment strategies.
SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer
Authors: Yang Hongjuan , Sui Lei , Cai Cuicui , Chu Huijun , Diao Yuchao 
Published: February 2024

Abstract
Background
Ovarian cancer (OC) is the most lethal gynecologic malignant tumour. The mechanism promoting OC initiation and progression remains unclear. SET domain bifurcated histone lysine methyltransferase 1(SETDB1) acts as an oncogene in a variety of tumours. This study aims to explore the role of SETDB1 in OC.

Methods
GEO, TCGA, CSIOVDB and CPTAC databases jointly analysed SETDB1 mRNA and protein expression. Effect of SETDB1 expression on the clinical prognosis of OC patients was analysed through online Kaplan‒Meier plotter and CSIOVDB database. Then, the effect of SETDB1 in OC cells progression and mobility was examined using MTT, EdU, colony formation and transwell assay. Additionally, Cistrome DB database was used to visualize the binding of SETDB1 protein and splicing factor 3b subunit 4 (SF3B4) promoter, and dual-luciferase reporter gene assay was performed to confirm the interaction. Finally, bioinformatics analysis was employed to reveal the relationship between SETDB1 and the microenvironment of OC.

Results
In the present study, we found that SETDB1 was obviously upregulated in OC and its overexpression predicted poor prognosis of OC patients. Then, we verified that SETDB1 promoted the progression and motility of OC cells in vitro. Knockdown of SETDB1 had the opposite effect. Further research showed that SETDB1 acted as a transcription factor to activate SF3B4 expression. SF3B4 knockdown impaired the effect of SETDB1 to promote the proliferative capacity and motility of OC cells. Finally, the results of bioinformatics analysis confirmed that SETDB1 regulated the immune microenvironment of ovarian cancer.

Conclusion
SETDB1 promoted ovarian cancer progression by upregulating the expression of SF3B4 and inhibiting the tumour immunity. SETDB1 may be a promising prognostic and therapeutic marker for OC.
How many sites should an orthopedic trauma prospective multicenter trial have? A marginal analysis of the Major Extremity Trauma Research Consortium completed trials
Authors: Allen Lauren , O’Toole Robert V. , Bosse Michael J. , Obremskey William T. , Archer Kristin R. , Cannada Lisa K. , Shores Jaimie , Reider Lisa M. , Frey Katherine P. , Carlini Anthony R. , Staguhn Elena D. , Castillo Renan C. 
Published: February 2024

Abstract
Background
Multicenter trials in orthopedic trauma are costly, yet crucial to advance the science behind clinical care. The number of sites is a key cost determinant. Each site has a fixed overhead cost, so more sites cost more to the study. However, more sites can reduce total costs by shortening the study duration. We propose to determine the optimal number of sites based on known costs and predictable site enrollment.

Methods
This retrospective marginal analysis utilized administrative and financial data from 12 trials completed by the Major Extremity Trauma Research Consortium. The studies varied in size, design, and clinical focus. Enrollment across the studies ranged from 1054 to 33 patients. Design ranged from an observational study with light data collection to a placebo-controlled, double-blinded, randomized controlled trial. Initial modeling identified the optimal number of sites for each study and sensitivity analyses determined the sensitivity of the model to variation in fixed overhead costs.

Results
No study was optimized in terms of the number of participating sites. Excess sites ranged from 2 to 39. Excess costs associated with extra sites ranged from $17K to $330K with a median excess cost of $96K. Excess costs were, on average, 7% of the total study budget. Sensitivity analyses demonstrated that studies with higher overhead costs require more sites to complete the study as quickly as possible.

Conclusions
Our data support that this model may be used by clinical researchers to achieve future study goals in a more cost-effective manner.

Trial registration
Please see Table 1 for individual trial registration numbers and dates of registration.
Pro-inflammatory feedback loops define immune responses to pathogenic Lentivirus infection
Authors: Wilk Aaron J. , Marceau Joshua O. , Kazer Samuel W. , Fleming Ira , Miao Vincent N. , Galvez-Reyes Jennyfer , Kimata Jason T. , Shalek Alex K. , Holmes Susan , Overbaugh Julie , Blish Catherine A. 
Published: February 2024

Abstract
Background
The Lentivirus human immunodeficiency virus (HIV) causes chronic inflammation and AIDS in humans, with variable rates of disease progression between individuals driven by both host and viral factors. Similarly, simian lentiviruses vary in their pathogenicity based on characteristics of both the host species and the virus strain, yet the immune underpinnings that drive differential Lentivirus pathogenicity remain incompletely understood.

Methods
We profile immune responses in a unique model of differential lentiviral pathogenicity where pig-tailed macaques are infected with highly genetically similar variants of SIV that differ in virulence. We apply longitudinal single-cell transcriptomics to this cohort, along with single-cell resolution cell-cell communication techniques, to understand the immune mechanisms underlying lentiviral pathogenicity.

Results
Compared to a minimally pathogenic lentiviral variant, infection with a highly pathogenic variant results in a more delayed, broad, and sustained activation of inflammatory pathways, including an extensive global interferon signature. Conversely, individual cells infected with highly pathogenic Lentivirus upregulated fewer interferon-stimulated genes at a lower magnitude, indicating that highly pathogenic Lentivirus has evolved to partially escape from interferon responses. Further, we identify CXCL10 and CXCL16 as important molecular drivers of inflammatory pathways specifically in response to highly pathogenic Lentivirus infection. Immune responses to highly pathogenic Lentivirus infection are characterized by amplifying regulatory circuits of pro-inflammatory cytokines with dense longitudinal connectivity.

Conclusions
Our work presents a model of lentiviral pathogenicity where failures in early viral control mechanisms lead to delayed, sustained, and amplifying pro-inflammatory circuits, which in turn drives disease progression.
Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification
Authors: Wang Xinan , Zhang Ziwei , Ding Yi , Chen Tony , Mucci Lorelei , Albanes Demetrios , Landi Maria Teresa , Caporaso Neil E. , Lam Stephen , Tardon Adonina , Chen Chu , Bojesen Stig E. , Johansson Mattias , Risch Angela , Bickeböller Heike , Wichmann H-Erich , Rennert Gadi , Arnold Susanne , Brennan Paul , McKay James D. , Field John K. , Shete Sanjay S. , Le Marchand Loic , Liu Geoffrey , Andrew Angeline S. , Kiemeney Lambertus A. , Zienolddiny-Narui Shan , Behndig Annelie , Johansson Mikael , Cox Angie , Lazarus Philip , Schabath Matthew B. , Aldrich Melinda C. , Hung Rayjean J. , Amos Christopher I. , Lin Xihong , Christiani David C. 
Published: February 2024

Abstract
Background
Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored.

Methods
Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold.

Results
Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12–3.50, P-value = 4.13 × 10−15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99–2.49, P-value = 5.70 × 10−46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72–0.74).

Conclusions
Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.
The effectiveness of fatigue on repositioning sense of lower extremities: systematic review and meta-analysis
Authors: Sayyadi Parisa , Minoonejad Hooman , Seidi Foad , Shikhhoseini Rahman , Arghadeh Ramin 
Published: February 2024

Abstract
Introduction
An injury can significantly harm both individual and team performance. One of the most important risk factors for sports-related injuries, especially non-collision injuries, is fatigue. It seems that poor proprioception may play an essential role to impose athletes to further injuries. This systematic review and meta-analysis aimed to examine the effectiveness of fatigue on the repositioning sense of the lower extremity joints.

Method
The electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar were systematically searched from inception to 11January 2024. The obtained records were exported to the EndNote Software version 8. Then, two investigators examined the records independently to find eligible studies based on the inclusion/exclusion criteria. In the case of disagreements, a consequence method was utilized. The quality of the eligible studies was evaluated using the Downs and Black checklist. Comprehensive Meta-Analysis (CMA) software ver. 3 software was used for statistical analysis. Q-test and I2 were employed to examine the data homogeneity. In addition, considering the risk of bias, the Funnel Plot and trim-and-fill method were used.

Results
After reviewing the titles and abstracts of 3883 studies found in the selected databases, 43 articles were found to be eligible to include in meta-analyses. The results showed that fatigue led to a significant increase in the active absolute error of the knee (SDM = 0.524, 95% CI = 0.406–0.841), ankle in the horizontal plane (SDM = 0.541, 95% CI = 0.367–0.715), ankle in the sagittal plane (SDM = 0.443, 95% CI = 0.088–0.798), and hip (SDM = 0.988, 95% CI = 0.135–1.841). However, fatigue had no significant effects on the passive absolute error of the knee and ankle in horizontal plane and relative angular error of the knee.

Conclusion
Fatigue can diminish the active joint position sense of the lower extremities and thus may increase the risk of injury by reducing proprioception. Therefore, future research could be conducted to investigate the potential impact of integrated fatigue-mitigating exercises into athletes’ training programs, with the aim of reducing the incidence of sports-related injuries.