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Abstract Background and objectives Currently, research on the role of B cells in esophageal cancer (EC) is limited, and existing studies on their impact are controversial. Therefore, this study was conducted to elucidate the complex causal relationship between B cells and EC, expand the understanding of esophageal cancer immunology. Methods Bidirectional two-sample Mendelian randomization (MR) was performed to assess the causal relationships between 190 B cell phenotypes and EC. To complement the MR analysis, Bayesian Weighted Mendelian Randomization (BWMR) was employed, and sensitivity analyses were conducted to evaluate the robustness of the findings. Positive results were further validated in independent cohorts of esophageal cancer studies. In addition, RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) were utilized for validation, incorporating B cell-related gene expression analysis and functional enrichment analysis to support the MR findings. Results In the primary analysis, significant causal relationships were observed between 5 B cell types and the risk of EC; the onset of EC was causally linked to 3 B cell phenotypes. Validation in other cohorts revealed that 4 outcomes aligned with the primary analysis, included were CD19 on IgD + CD38-, CD20 on IgD- CD27-, CD20 on IgD- CD38br, and CD38 on PB/PC. Further validation using RNA-seq data showed that CD38 mRNA was significantly overexpressed in EC tissues, whereas CD19 and MS4A1 mRNA levels did not differ significantly between tumor and normal tissues. Functional enrichment analysis revealed that CD19, MS4A1, and CD38 are involved in multiple tumor-related immune pathways, suggesting their pivotal role in regulating the tumor immune microenvironment. Conclusions Our study suggests a potential connection between B cell phenotypes and EC through bidirectional two-sample MR combined with BWMR analysis, providing a preliminary basis for future research.

Abstract Background In recent decades, early rehabilitation after Achilles tendon rupture (ATR) repair has been proposed. The aim of this prospective cohort study was to compare different immobilisation durations in order to determine the optimal duration after open surgery for ATR repair. Methods This study included 1088 patients (mean age, 34.9 ± 5.9 years) who underwent open surgery for acute ATR repair. The patients were categorised into four groups (A, B, C, and D) according to postoperative immobilisation durations of 0, 2, 4, and 6 weeks, respectively. All patients received the same suture technique and a similar rehabilitation protocol after brace removal,; they were clinically examined at 2, 4, 6, 8, 10, 12, 14, and 16 weeks postoperatively, with a final follow-up at a mean of 19.0 months. The primary outcome was the recovery time for the one-leg heel-rise height (OHRH). Secondary outcomes included the time required to return to light exercise (LE) and the recovery times for the range of motion (ROM). Data regarding the surgical duration, complications, the visual analogue scale (VAS) score for pain, the Achilles tendon Total Rupture Score (ATRS), and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score were also collected. Results The recovery times for OHRH, LE, and ROM were significantly shorter in groups A and B than in groups C and D (P

Livestock are the largest source of anthropogenic methane (CH4) emissions, and in intensive dairy systems, manure management can contribute half of livestock CH4. Recent policies such as California's short-lived climate pollutant reduction law (SB 1383) and the Global Methane Pledge call for cuts to livestock CH4 by 2030. However, investments in CH4 reduction strategies are primarily aimed at liquid dairy manure, whereas stockpiled solids remain a large source of CH4. Here, we measure the CH4 and net greenhouse gas reduction potential of dairy manure biochar-composting, a novel manure management strategy, through a composting experiment and life-cycle analysis. We found that biochar-composting reduces CH4 by 79%, compared to composting without biochar. In addition to reducing CH4 during composting, we show that the added climate benefit from biochar production and application contributes to a substantially reduced life-cycle global warming potential for biochar-composting: -535 kg CO2e Mg-1 manure compared to -194 kg CO2e Mg-1 for composting and 102 kg CO2e Mg-1 for stockpiling. If biochar-composting replaces manure stockpiling and complements anaerobic digestion, California could meet SB 1383 with 132 less digesters. When scaled up globally, biochar-composting could mitigate 1.59 Tg CH4 yr-1 while doubling the climate change mitigation potential from dairy manure management.

BackgroundMorphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.MethodsInterregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.ResultsAcross the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.ConclusionsOur findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Background and objectivesHashimoto’s thyroiditis (HT), a chronic autoimmune disorder impacting thyroid function, is a growing public health concern. The relationship between Treg cells and HT has been extensively studied, with Treg cells considered crucial in suppressing HT progression. However, these studies have mainly been observational, limiting our understanding of Treg cells’ impact on HT risk. Leveraging large datasets, we utilized Mendelian randomization (MR) analysis to examine the causal association between Treg cell biomarkers and HT, providing additional validation for these relationships.MethodsComprehensive two-sample Mendelian randomization analysis was performed to determine the causal association between Treg cells signatures and HT in this study. Based on publicly available genetic data, we explored causal associations between 165 Treg cells signatures and HT risk.ResultsThe European cohort study has identified five Treg cell phenotypes that causally protect against HT risk. Resting Treg %CD4 (OR = 0.975, 95% CI = 0.954~0.998, P = 0.030); CD4 on resting Treg (OR = 0.938, 95% CI = 0.882~0.997, P = 0.041; CD28- CD8dim %CD8dim (OR = 0.983, 95% CI = 0.969~0.998, P = 0.030); CD25 on CD39+ resting Treg (OR = 0.926, 95% CI = 0.864~0.991, P = 0.026); 5) CD28 on activated & secreting Treg (OR = 0.969, 95% CI = 0.942~0.996, P = 0.025). The Asian cohort study has identified four Treg cell phenotypes negatively correlated with the risk of HT. CD25hi %T cell (OR = 0.635, 95% CI = 0.473~852, P = 0.002); CD4 Treg %CD4 (OR = 0.829, 95% CI = 0.687~1.000, P = 0.050); CD127-CD8br %T cell (OR = 0.463, 95% CI =0.311~0.687, P< 0.001); CD3 on resting Treg (OR = 0.786, 95% CI = 0.621~0.994, P = 0.044).ConclusionOur study has demonstrated the close connection between Treg cells and HT by genetic means, thus providing foundational basis for future research.

Objective Surgical strategy for spinal kyphosis in patients with ankylosing spondylitis (AS) has been challenging. Pedicle subtraction osteotomy (PSO) through a minimally invasive (MI) approach has been developed with promising clinical outcomes. We aimed to compare the effectiveness and safety of PSO via an MI approach and a standard posterior approach (SPA) for treating AS‐related spinal kyphosis. Methods A total of 41 patients with AS‐related spinal kyphosis who underwent PSO through an MI approach (MI surgery [MIS] group: n = 25) or SPA (SPA group: n = 16) between January 2015 and July 2020 were retrospectively included. Spinopelvic parameters were evaluated before the surgery, immediately after the surgery, and at the 2‐year follow‐up. Clinical data including operative time, estimated blood loss, blood transfusion, level of fusion, incision length, bed rest period, length of hospitalization, and surgical complications were compared between the two groups. The Scoliosis Research Society outcomes instrument‐22 (SRS‐22) was administered to assess patients' quality of life at the latest follow‐up. Comparisons between the two groups were performed using independent sample t‐test or Chi‐square test. Results Characteristics and baseline kyphosis of the two groups were matched. At the 2‐year follow‐up, in the MIS group, the average correction values of the sagittal vertical axis and global kyphosis (GK) were 9.5 cm and 44.3°, respectively. Compared with the SPA group, the MIS group had similar correction values and correction losses after surgery. No obvious differences were observed in any radiographic parameters, except for GK, immediately after surgery and at the 2‐year follow‐up between the two groups (p > 0.05). The MIS group had a significantly shorter operative time, lesser blood loss, lesser transfusion volume, shorter fusion level, and lesser time to mobilization than did the SPA group. Higher average functional activity scores of SRS‐22 were obtained in the MIS group than in the SPA group. Conclusion Mini‐open PSO may be an effective alternative to the SPA for treating AS‐related spinal kyphosis, with comparable correction effect, lesser surgical trauma and faster recovery. This comparative study may provide valuable guidance for surgical decision‐making and patient counseling.