bluuebunny/crossref_metadata_2025 huggingface dataset:
Number of intra-operative cyclic knee motion required to achieve stable graft tension in anterior cruciate ligament reconstruction; a prospective clinical study
Authors: Horii Manato , Akagi Ryuichiro , Watanabe Shotaro , Enomoto Takahiro , Hosokawa Hiroaki , Ohtori Seiji , Sasho Takahisa
Published: February 2024

Background

Applying pretension by cyclic knee motion immediately before graft fixation in anterior cruciate ligament (ACL) reconstruction surgery decreases graft elongation during the postoperative course. However, the expected change in graft tension caused by cyclic knee motion remains unclear. We measured graft tension changes caused by cyclic knee motion during double-bundle ACL reconstruction.

Methods

We included 39 patients undergoing primary anatomical double-bundle ACL reconstruction with autologous hamstrings as graft sources, at multiple centers between February 2021 and August 2022. After securing the anteromedial (AM) and posterolateral (PL) bundle grafts to the femoral cortex, they were initially tensioned to 40 N per bundle. After 10 cycles of knee extension and flexion motion, ranging from 0 to 90–110°, tension was re-measured and re-tensioned to 40 N if the graft tension had decreased. This was repeated thrice for 10 cycles on each graft. Every 10 cycles, we recorded graft tension changes (ΔGT) and compared the mean ΔGT in the AM and PL bundles. Furthermore, we assessed relationships between total ΔGT in each bundle, age, sex, and graft diameter.

Results

Twenty-five women and 14 men with a mean age of 27.4 ± 12.4 years were included. The mean ΔGT in AM and PL bundles after every 10 cycles were 6.6 ± 3.7 N, 3.0 ± 2.3 N, 1.4 ± 1.5 N, and 9.9 ± 3.8 N, 4.9 ± 2.6 N, and 2.5 ± 1.9 N, respectively. There were significant differences in ΔGT in both bundles after every 10 cycles (p < 0.01). ΔGT in the AM bundle was significantly lower than in the PM bundle at the same number of cycles (p < 0.01). No correlation was observed between ΔGT in either bundle and age, sex, or graft diameter.

Conclusions

The initially applied graft tension decreased by intra-operative cyclic knee movement, and the changes in graft tension decreased after retention and repeated cycles. Three sets of 10 cycles knee motion may avoid initial tension loss of the hamstring autograft in the early phase after double-bundle ACL reconstruction.
Progression of vertebral deformity of prevalent vertebral fractures in the elderly: a population-based study
Authors: Akeda Koji , Nakase Kazuma , Yamada Junichi , Takegami Norihiko , Fujiwara Tatsuhiko , Sudo Akihiro
Published: February 2024

Background

Little is known about the progression pattern of vertebral deformities in elderly patients with prevalent vertebral fractures. This population-based cohort study investigated the incidence, progression pattern, and risk factors of vertebral deformity in prevalent vertebral fractures over a finite period of four years in a population-based cohort study.

Methods

A total of 224 inhabitants of a typical mountain village underwent medical examinations every second year from 1997 to 2009, and each participant was followed up for four years. The extent (mild, moderate, severe) and type (wedge, biconcave, crush) of prevalent vertebral fractures on spinal radiographs were evaluated using the Genant semi-quantitative method. Of these participants, 116 with prevalent vertebral fractures at baseline (32 men and 84 women; mean age: 70.0 years) were included in this study. The progression patterns of the 187 vertebral fractures with mild and moderate deformities (except severe deformity) were evaluated. Logistic regression analysis was used to identify the risk factors associated with deformity progression.

Results

The progression of vertebral deformities was identified in 13.4% (25 vertebral fractures) of the total 187 prevalent (mild and moderate) vertebral fracture deformities over four years. Among the three deformity types, the prevalence of deformity progression was significantly lower in wedge-type vertebral fractures (P < 0.05). Age and number of prevalent vertebral fractures per participant were independent risk factors associated with the progression of prevalent vertebral deformities.

Conclusion

This study clarified the natural history of the progression pattern of vertebral deformities in radiographic prevalent vertebral fractures in elderly individuals. Multiple vertebral fractures in the elderly present a risk for the progression of vertebral deformities.
The role of oral microbiota in the development of oral mucositis in pediatric oncology patients treated with antineoplastic drugs: a systematic review
Authors: Filetici Pierfrancesco , Gallottini Sofia Germana , Corvaglia Andrea , Amendolea Martina , Sangiovanni Roberta , Nicoletti Fabrizio , D’Addona Antonio , Dassatti Leonardo
Published: February 2024

Background

In the pediatric oncology population, oral mucositis as a consequence of chemotherapy is a highly prevalent complication which strongly affects both the quality of life and treatment possibilities of the patients. Still, the etiopathological mechanisms carrying to its development are not fully understood, although a possible role of oral dysbiosis has been previously investigated with unclear conclusions. The aim of this systematic review was to assess the available evidence on the role of microbiota in the development of oral mucositis.

Methods

A systematic literature search was performed following PRISMA guidelines. Three electronic databases were searched up until April 2023 and a following manual search included the reference lists of the included studies and reviews. Studies reporting microbiological and clinical data of pediatric patients treated by antineoplastic drugs were included.

Results

Thirteen studies met the inclusion criteria, reporting an average mucositis prevalence of 57,6%. Candida albicans infections were frequently observed in studies performing microbiological analysis on oral lesions, in contrast with the low rate detection of the Herpes simplex viruses. Bacterial species such as coagulase-negative Staphylococci and Streptococcus viridans were detected more frequently on lesion sites. Studies reporting a quantitative analysis of the general flora did not show comparable results. Risk of bias assessment among studies was generally considered high or very high.

Conclusions

While the specific role of certain microbiological agents, such as Candida albicans, was frequently reported among studies, data regarding the general dynamics of oral microbiota in the development of oral mucositis are lacking in the current literature. Thus, more studies are needed to provide the knowledge required in order to improve protocols for the prevention and treatment of this threatening complication.
A new chromosome-scale duck genome shows a major histocompatibility complex with several expanded multigene families
Authors: Hu Jiaxiang , Song Linfei , Ning Mengfei , Niu Xinyu , Han Mengying , Gao Chuze , Feng Xingwei , Cai Han , Li Te , Li Fangtao , Li Huifang , Gong Daoqing , Song Weitao , Liu Long , Pu Juan , Liu Jinhua , Smith Jacqueline , Sun Honglei , Huang Yinhua
Published: February 2024

Background

The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A virus (IAV), harbors almost all subtypes of IAVs and resists to many IAVs which cause extreme virulence in chicken and human. However, the response of duck’s adaptive immune system to IAV infection is poorly characterized due to lack of a detailed gene map of the major histocompatibility complex (MHC).

Results

We herein reported a chromosome-scale Beijing duck assembly by integrating Nanopore, Bionano, and Hi-C data. This new reference genome SKLA1.0 covers 40 chromosomes, improves the contig N50 of the previous duck assembly with highest contiguity (ZJU1.0) of more than a 5.79-fold, surpasses the chicken and zebra finch references in sequence contiguity and contains a complete genomic map of the MHC. Our 3D MHC genomic map demonstrated that gene family arrangement in this region was primordial; however, families such as AnplMHCI, AnplMHCIIβ, AnplDMB, NKRL (NK cell receptor-like genes) and BTN underwent gene expansion events making this area complex. These gene families are distributed in two TADs and genes sharing the same TAD may work in a co-regulated model.

Conclusions

These observations supported the hypothesis that duck’s adaptive immunity had been optimized with expanded and diversified key immune genes which might help duck to combat influenza virus. This work provided a high-quality Beijing duck genome for biological research and shed light on new strategies for AIV control.
The functional role of spatial anisotropies in ensemble perception
Authors: Tiurina Natalia A. , Markov Yuri A. , Whitney David , Pascucci David
Published: February 2024

Background

The human brain can rapidly represent sets of similar stimuli by their ensemble summary statistics, like the average orientation or size. Classic models assume that ensemble statistics are computed by integrating all elements with equal weight. Challenging this view, here, we show that ensemble statistics are estimated by combining parafoveal and foveal statistics in proportion to their reliability. In a series of experiments, observers reproduced the average orientation of an ensemble of stimuli under varying levels of visual uncertainty.

Results

Ensemble statistics were affected by multiple spatial biases, in particular, a strong and persistent bias towards the center of the visual field. This bias, evident in the majority of subjects and in all experiments, scaled with uncertainty: the higher the uncertainty in the ensemble statistics, the larger the bias towards the element shown at the fovea.

Conclusion

Our findings indicate that ensemble perception cannot be explained by simple uniform pooling. The visual system weights information anisotropically from both the parafovea and the fovea, taking the intrinsic spatial anisotropies of vision into account to compensate for visual uncertainty.
Comprehensive analysis reveals the prognostic and immunogenic characteristics of DNA methylation regulators in lung adenocarcinoma
Authors: Huang Jing , Huang Chujian , Huang Can , Xiang Zichang , Ni Yao , Zeng Jian , Cai Songhua
Published: February 2024

DNA methylation regulators (DMRs) play a key role in DNA methylation, thus mediating tumor occurrence, metastasis, and immunomodulation. However, the effects of DMRs on clinical outcomes and immunotherapy response remain unexplored in lung adenocarcinoma (LUAD). In this study, eight LUAD cohorts and one immunotherapeutic cohort of lung cancer were utilized. We constructed a DNA methylation regulators-related signature (DMRRS) using univariate and multivariate COX regression analysis. The DMRRS-defined low-risk group was preferentially associated with favorable prognosis, tumor-inhibiting microenvironment, more sensitivity to several targeted therapy drugs, and better immune response. Afterward, the prognostic value and predictive potential in immunotherapy response were validated. Collectively, our findings uncovered that the DMRRS was closely associated with the tumor immune microenvironment and could effectively predict the clinical outcome and immune response of LUAD patients.
MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence
Authors: Lu Fang , Yao Li-peng , Gao Dan-dan , Alinejad Tahereh , Jiang Xin-qing , Wu Qi , Zhai Qiao-cheng , Liu Ming , Zhu Sheng-mei , Qian Mao-xiang , Xu Li-feng , Chen Cheng-shui , Zhang Feng
Published: February 2024

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.
Impact of ambient temperature on respiratory disease: a case-crossover study in Seoul
Authors: Lee Hyewon , Yoon Hee-Young
Published: February 2024

Background

Respiratory diseases contribute to global morbidity and mortality, and temperature is a significant factor. We investigated the association between ambient temperature and emergency department (ED) visits for various respiratory diseases in Seoul, South Korea.

Methods

Using data from the National Emergency Department Information System (2008–2017), we analysed 1,616,644 ED visits for respiratory diseases, categorised according to the Korean Standard Classification of Diseases 7th revision codes (J00-J99). Using a time-stratified case-crossover design and a distributed lag nonlinear model, we investigated the effect of temperature exposure on ED visits for respiratory diseases, calculating the relative risk (RR) for the maximum risk temperature (MaxRT) of both cold and hot extremes compared to the minimum risk temperature (MinRT).

Results

Cold temperatures (MaxRT: -9.0 °C) resulted in a 2.68-fold increase (RR = 2.68, 95% CI = 2.26–3.14) in ED visits for total respiratory diseases, while hot temperatures (MaxRT: 29.4 °C) led to a 1.26-fold increase (RR = 1.26, 95% CI = 1.11–1.42) compared to the MinRT (24.8 °C). Cold temperatures increased the risk of most respiratory diseases, except interstitial lung disease, whereas hot temperatures increased ED visits for acute upper respiratory infections and influenza. Cold temperatures increased ED visits for all age groups, especially those aged 18–64 (RR = 3.54, 95% CI = 2.90–4.33), while hot temperatures significantly affected those < 18 (RR = 1.45, 95% CI = 1.27–1.66). The risk levels were similar in both males and females, regardless of hot and cold temperatures.

Conclusion

Our findings underscore the significant impact of both cold and heat exposure on ED visits for respiratory diseases, with varying intensities and risk profiles across different population groups.
Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia
Authors: Yang Hu-Qin , Sun Han , Li Kang , Shao Ming-Ming , Zhai Kan , Tong Zhao-Hui
Published: February 2024

Background

Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited.

Methods

In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models.

Results

Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP.

Conclusion

Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP’s cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.
Efficacy and safety of anticoagulant for treatment and prophylaxis of VTE patients with renal insufficiency: a systemic review and meta-analysis
Authors: Ma Shuangshuang , Fan Guohui , Xu Feiya , Zhang Xiaomeng , Chen Yinong , Tao Yuzhi , Li Yishan , Lyu Yanshuang , Yang Peiran , Wang Dingyi , Zhai Zhenguo , Wang Chen
Published: February 2024

Patients with venous thromboembolism (VTE) comorbid renal insufficiency (RI) are at higher risk of bleeding and thrombosis. Recommendations in guidelines on anticoagulation therapy for those patients remain ambiguous. The goal of this study is to compare the efficacy and safety between different anticoagulant regimens in VTE patients comorbid RI at different stages of treatment and prophylaxis. We performed English-language searches of Pubmed, EMBASE, and Web of Science (inception to Nov 2022). RCTs evaluated anticoagulants for VTE treatment at the acute phase, extension phase, and prophylaxis in patients with RI and reported efficacy and safety outcomes were selected. The methodological quality of the studies was assessed at the outcome level using the risk-of-bias assessment tool developed by the Cochrane Bias Methods Group. A meta-analysis of twenty-five RCTs was conducted, comprising data from twenty-three articles, encompassing a total of 9,680 participants with RI. In the acute phase, the risk of bleeding was increased with novel oral anticoagulants (NOACs) compared to LMWH (RR 1.29, 95% CI 1.04–1.60). For the prophylaxis of VTE, NOACs were associated with an elevated risk of bleeding compared with placebo (RR 1.31, 95%CI 1.02–1.68). In comparison to non-RI patients, both NOACs and vitamin K antagonists (VKA) could increase the risk of bleeding among RI patients (RR 1.45, 95%CI 1.14–1.84 and RR 1.53, 95%CI 1.25–1.88, respectively) during acute phase, while NOACs may increase the incidence of VTE in RI population (RR 1.74, 95%CI 1.29–2.34). RI patients who are under routine anticoagulation have a significantly higher risk of adverse outcomes. LMWH is the most effective and safe option for VTE treatment or prophylaxis in patients with RI.
GOLGA7 is essential for NRAS trafficking from the Golgi to the plasma membrane but not for its palmitoylation
Authors: Liu Chenxuan , Jiao Bo , Wang Peihong , Zhang Baoyuan , Gao Jiaming , Li Donghe , Xie Xi , Yao Yunying , Yan Lei , Qin Zhenghong , Liu Ping , Ren Ruibao
Published: February 2024

NRAS mutations are most frequently observed in hematological malignancies and are also common in some solid tumors such as melanoma and colon cancer. Despite its pivotal role in oncogenesis, no effective therapies targeting NRAS has been developed. Targeting NRAS localization to the plasma membrane (PM) is a promising strategy for cancer therapy, as its signaling requires PM localization. However, the process governing NRAS translocation from the Golgi apparatus to the PM after lipid modification remains elusive. This study identifies GOLGA7 as a crucial factor controlling NRAS’ PM translocation, demonstrating that its depletion blocks NRAS, but not HRAS, KRAS4A and KRAS4B, translocating to PM. GOLGA7 is known to stabilize the palmitoyltransferase ZDHHC9 for NRAS and HRAS palmitoylation, but we found that GOLGA7 depletion does not affect NRAS’ palmitoylation level. Further studies show that loss of GOLGA7 disrupts NRAS anterograde trafficking, leading to its cis-Golgi accumulation. Remarkably, depleting GOLGA7 effectively inhibits cell proliferation in multiple NRAS-mutant cancer cell lines and attenuates NRASG12D-induced oncogenic transformation in vivo. These findings elucidate a specific intracellular trafficking route for NRAS under GOLGA7 regulation, highlighting GOLGA7 as a promising therapeutic target for NRAS-driven cancers.
The current state of complex systems research on socioeconomic inequalities in health and health behavior—a systematic scoping review
Authors: Mudd Andrea L. , Bal Michèlle , Verra Sanne E. , Poelman Maartje P. , de Wit John , Kamphuis Carlijn B. M.
Published: February 2024

Background

Interest in applying a complex systems approach to understanding socioeconomic inequalities in health is growing, but an overview of existing research on this topic is lacking. In this systematic scoping review, we summarize the current state of the literature, identify shared drivers of multiple health and health behavior outcomes, and highlight areas ripe for future research.

Methods

SCOPUS, Web of Science, and PubMed databases were searched in April 2023 for peer-reviewed, English-language studies in high-income OECD countries containing a conceptual systems model or simulation model of socioeconomic inequalities in health or health behavior in the adult general population. Two independent reviewers screened abstracts and full texts. Data on study aim, type of model, all model elements, and all relationships were extracted. Model elements were categorized based on the Commission on Social Determinants of Health framework, and relationships between grouped elements were visualized in a summary conceptual systems map.

Results

A total of 42 publications were included; 18 only contained a simulation model, 20 only contained a conceptual model, and 4 contained both types of models. General health outcomes (e.g., health status, well-being) were modeled more often than specific outcomes like obesity. Dietary behavior and physical activity were by far the most commonly modeled health behaviors. Intermediary determinants of health (e.g., material circumstances, social cohesion) were included in nearly all models, whereas structural determinants (e.g., policies, societal values) were included in about a third of models. Using the summary conceptual systems map, we identified 15 shared drivers of socioeconomic inequalities in multiple health and health behavior outcomes.

Conclusions

The interconnectedness of socioeconomic position, multiple health and health behavior outcomes, and determinants of socioeconomic inequalities in health is clear from this review. Factors central to the complex system as it is currently understood in the literature (e.g., financial strain) may be both efficient and effective policy levers, and factors less well represented in the literature (e.g., sleep, structural determinants) may warrant more research. Our systematic, comprehensive synthesis of the literature may serve as a basis for, among other things, a complex systems framework for socioeconomic inequalities in health.
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

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

Backgrounds

The 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.

Methods

Seventy-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).

Results

There 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).

Conclusion

The 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

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

Entorhinal 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

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

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

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

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

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

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.