Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced survival of total knee arthroplasty after previous unicompartmental knee arthroplasty compared with previous high tibial osteotomy: a propensity-score weighted mid-term cohort study based on 2,133 observations from the Danish Knee Arthroplasty Registry

Background and purpose — Both medial unicompartmental knee arthroplasties (UKA) and high tibial osteotomies (HTO) are reliable treatments for isolated medial knee osteoarthritis. However, both may with time need conversion to a total knee arthroplasty (TKA). We conducted the largest nationwide registry comparison of the survival of TKA following UKA with TKA following HTO. Patients and methods — From the Danish Knee Arthroplasty Registry, aseptic conversions to TKA from UKA and TKA converted from HTO within the period of 1997–2018 were retrieved. The Kaplan–Meier method and the Cox proportional hazards regression were used to estimate the survival and hazard ratio (HR) for revision, considering confounding by indication utilizing propensity-score based inverse probability of treatment weighting (PS-IPTW). Results — PS-IPTW yielded a well-balanced pseudo-cohort (standard mean difference (SMD) < 0.1 for all covariates, except implant supplementation) of 963.8 TKAs following UKA and 1139.1 TKAs following HTO. The survival of TKA following UKA was significantly less than that of TKA following HTO with a 5-year estimated survival of 0.88 (95% confidence interval (CI) 0.85–0.90) and 0.94 (CI 0.93–0.96), respectively. The differences in survival corresponded to an implant-supplementation adjusted HR of 2.7 (CI 2.4–3.1) for TKA following UKA compared with TKA following HTO. Interpretation — Previous UKA more than doubled the revision risk of a subsequent TKA compared with previous HTO. This potential risk should be considered in the shared treatment decision of patients who are candidates for both UKA and HTO.
Predictive factors and prognostic value of pathologic complete response of ipsilateral supraclavicular lymph nodes in breast cancer after neoadjuvant chemotherapy.

Background Breast cancer with ipsilateral supraclavicular lymph node metastasis is one of the indicators of poor prognosis. Patients who attain pathologic complete response in breast and axillary sites have improved survival and are highest in aggressive HR-HER2- and HER2-positive tumor subtypes. However, there is no study on the related factors and prognostic value of supraclavicular pathologic complete response in breast cancer after neoadjuvant chemotherapy. The aim of our work was to investigate the factors and prognostic significance of pathologic complete response of ipsilateral supraclavicular lymph node metastasis in breast cancer after neoadjuvant chemotherapy. Methods A total of 214 patients with breast cancer who had primary ISLN metastasis, receiving NAC and subsequent ISLN dissection, were retrospectively and consecutively reviewed. Univariate and multivariate analyses were performed using χ2 test and the logistic regression model, and the prognosis was analyzed by Kaplan-Meier curve. Results All patients included were women who were 26-74 years old. The rate of supraclavicular pathologic complete response (pCR) was 53.7%. Multivariate analysis showed that the expression of Ki67, breast pCR, and axillary pCR were independent predictors of supraclavicular pCR (P<0.05). After a median follow-up of 16.2 months, the risk of recurrence and metastasis in patients with supraclavicular pCR was half reduced compared to that of the non-pCR group (HR 0.51, 95% CI, 0.32-0.80, P<0.01), mainly manifested in HR-HER2- and HER2-positive disease. Conclusions The expression level of Ki67, breast pCR, and axillary pCR were independent predictors of supraclavicular pCR. Supraclavicular pCR was an independent predictor of disease-free survival (DFS). Surgical removal of supraclavicular lymph nodes can accurately evaluate the rate of supraclavicular pCR, which is of great significance for patient prognosis.
Expression of two glutamate decarboxylase genes in Lactobacillus brevis during gamma-aminobutyric acid production with date residue extract

ABSTRACT Gamma-aminobutyric acid (GABA) is produced by Lactobacillus brevis using date residue fermentation. In this study, the GABA production method was improved, for which L. brevis strain JCM 1059T was the most efficient among the four L. brevis strains examined. This was presumably due to a difference in the expression level of the gene encoding glutamate decarboxylase that catalyzes GABA synthesis. Abbreviation GABA: gamma-aminobutyric acid
Super-Resolution Imaging Using a Novel High-Fidelity Antibody Reveals Close Association of the Neuronal Sodium Channel NaV1.6 with Ryanodine Receptors in Cardiac Muscle

Abstract The voltage-gated sodium channel [pore-forming subunit of the neuronal voltage-gated sodium channel (NaV1.6)] has recently been found in cardiac myocytes. Emerging studies indicate a role for NaV1.6 in ionic homeostasis as well as arrhythmogenesis. Little is known about the spatial organization of these channels in cardiac muscle, mainly due to the lack of high-fidelity antibodies. Therefore, we developed and rigorously validated a novel rabbit polyclonal NaV1.6 antibody and undertook super-resolution microscopy studies of NaV1.6 localization in cardiac muscle. We developed and validated a novel rabbit polyclonal antibody against a C-terminal epitope on the neuronal sodium channel 1.6 (NaV1.6). Raw sera showed high affinity in immuno-fluorescence studies, which was improved with affinity purification. The antibody was rigorously validated for specificity via multiple approaches. Lastly, we used this antibody in proximity ligation assay (PLA) and super-resolution STochastic Optical Reconstruction Microscopy (STORM) studies, which revealed enrichment of NaV1.6 in close proximity to ryanodine receptor (RyR2), a key calcium (Ca2+) cycling protein, in cardiac myocytes. In summary, our novel NaV1.6 antibody demonstrates high degrees of specificity and fidelity in multiple preparations. It enabled multimodal microscopic studies and revealed that over half of the NaV1.6 channels in cardiac myocytes are located within 100 nm of ryanodine receptor Ca2+ release channels.
Endovascular Treatment of Persistent Sciatic Artery Aneurysms With Primary Stenting: A Systematic Review of the Literature

Persistent sciatic artery (PSA) is an embryologic remnant of the internal iliac artery, and when is present, it undergoes aneurysmal degeneration in up to 60% of the cases. Endovascular repair is an increasingly utilized treatment strategy for PSA aneurysms (PSAAs). The objective was to demonstrate the safety and efficacy of the endovascular repair in patients with PSAA and to identify potential risk factors for loss of patency or limb loss. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and eligible studies were identified through search of the PubMed, Scopus, and Cochrane Central databases. Fifteen case reports, comprising 15 patients overall, were included. The median age of the patients was 68 years old (mean age 66 ± 13.4 years) with half of the reported patients being women. Most patients presented with progressive limb claudication, complaining about an enlarging palpable pulsatile buttock mass. The onset of symptoms was sudden in 78% of the reported cases. Additionally, the distal pulses on PSAA side were diminished or absent in 91% of the patients. Acute limb ischemia was the primary diagnosis in 75% of the cases. All patients underwent endovascular repair of the PSAA with a covered stent. Procedural outcomes were favorable in all patients demonstrating no symptoms recurrence, aneurysmal regression, or total obliteration evaluated by angiographic studies (computed tomography angiography [CTA] and angiogram). Periprocedural imaging evaluation was determined either with CTA or duplex ultrasound (DUS). Periprocedural complications included only 1 endoleak with distal dissection. This endoleak was identified after stent deployment and dissection distal to the aneurysm. Mean follow-up (with CTA and/or DUS) was 22 months, with all patients being asymptomatic with no recurrence of symptom. The endovascular treatment of PSAA with covered stent is safe and effective. Persistent sciatic artery aneurysms is associated with high procedural success, low periprocedural compilations, and favorable mid-term follow-up.
Staging Alzheimer’s disease in the brain and retina of B6.APP/PS1 mice by transcriptional profiling

Alzheimer’s disease (AD) is a common form of dementia characterized by amyloid plaque deposition, TAU pathology, neuroinflammation and neurodegeneration. Mouse models recapitulate some key features of AD. For instance, the B6.APP/PS1 model (carrying human transgenes for mutant forms of APP and PSEN1) shows plaque deposition and associated neuroinflammatory responses involving both astrocytes and microglia beginning around 6 months of age. However, in our colony, TAU pathology, significant neurodegeneration and cognitive decline are not apparent in this model even at older ages. Therefore, this model is ideal for studying neuroinflammatory responses to amyloid deposition. Here, RNA sequencing of brain and retinal tissue, generalized linear modeling (GLM), functional annotation followed by validation by immunofluorescence (IF) was performed in B6.APP/PS1 mice to determine the earliest molecular changes prior to and around the onset of plaque deposition (2-6 months of age). Multiple pathways were shown to be activated in response to amyloid deposition including the JAK/STAT and NALFD pathways. Putative, cell-specific targets of STAT3, a central component of the JAK/STAT pathway, were identified that we propose provide more precise options for assessing the potential for targeting activation of the JAK/STAT pathway as a treatment for human AD. In the retina, GLM predicted activation of vascular-related pathways. However, many of the gene expression changes comparing B6 with B6.APP/PS1 retina samples occurred prior to plaque onset (2 months of age). This suggests retinal changes in B6.APP/PS1 mice may be an artefact of overexpression of mutant forms of APP and PSEN1 providing limited translatability to human AD. Therefore, caution should be taken when using this mouse model to assess the potential of using the eye as a window to the brain for AD.
A Small Hypoxia Signature Predicted pCR Response to Bevacizumab in the Neoadjuvant GeparQuinto Breast Cancer Trial

Purpose: In breast cancer, bevacizumab increased pCR rate but not long-term survival and no predictive markers are available to identify patients with long-term benefit from the drug. Experimental Design: We profiled 289 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) biopsies of HER2-negative patients from the GeparQuinto trial of neoadjuvant chemotherapy ± bevacizumab by exome-capture RNA-sequencing (RNA-seq). In a prospectively planned study, we tested molecular signatures for response prediction. IHC validation was performed using tissue microarrays. Results: We found strong agreement of molecular and pathologic parameters as hormone receptors, grading, and lymphocyte infiltration in 221 high-quality samples. Response rates (49.3% pCR overall) were higher in basal-like (68.9%) and HER2-enriched (45.5%) than in luminal B (35.7%), luminal A (17.9%), and normal-like (20.0%) subtypes. T-cell (OR = 1.60; 95% confidence interval, 1.21–2.12; P = 0.001), proliferation (OR = 2.88; 95% CI, 2.00–4.15; P < 0.001), and hypoxia signatures (OR = 1.92; 95% CI, 1.41–2.60; P < 0.001) significantly predicted pCR in univariate analysis. In a prespecified multivariate logistic regression, a small hypoxia signature predicted pCR (OR = 2.40; 95% CI, 1.28–4.51; P = 0.006) with a significant interaction with bevacizumab treatment (P = 0.020). IHC validation using NDRG1 as marker revealed highly heterogenous expression within tissue leading to profound loss of sensitivity in TMA analysis, still a significant predictive value for pCR was detected (P = 0.025). Conclusions: Exome-capture RNA-seq characterizes small FFPE core biopsies by reliably detecting factors as for example ER status, grade, and tumor-infiltrating lymphocytes levels. Beside molecular subtypes and immune signatures, a small hypoxia signature predicted pCR to bevacizumab, which could be validated by IHC. The signature can have important applications for bevacizumab treatment in different cancer types and might also have a role for novel combination therapies of bevacizumab with immune checkpoint inhibition.
Comparison of efficacy between video-assisted thoracoscopic surgery and thoracotomy in children with mediastinal tumors: 6-year experience.

Background Video-assisted thoracic surgery (VATS) has been increasingly used in pediatric patients. We evaluated the outcomes of VATS and thoracotomy for pediatric mediastinal tumors. Methods A total of 137 patients who underwent surgery for mediastinal tumors at our department from March 2012 to September 2018 were recruited in this retrospective study. Forty-three patients were treated by VATS and ninety-four underwent thoracotomy (two patients who underwent open surgery were excluded from the study because they were lost to follow-up). Data including demographic information, tumor characteristics, operative time, conversion of surgery, blood transfusion, postoperative hospital stay, mortality and recurrence were collected and compared between the two groups. Results No significant difference was found in gender, age, weight and tumor distribution between the two groups. The number of patients with malignant tumors who underwent thoracotomy was significantly higher than those who received VATS (78.0% vs. 22.0%, P=0.04). Patients received thoracotomy had signiﬁcantly larger mean tumor diameter than those who underwent VATS (7.6±3.8 vs. 4.4±1.7 cm, P<0.001). The intraoperative transfusion rate in the thoracotomy group was significantly higher than that in the VATS group (67.4% vs. 14.0%, P<0.001), so was the amount of blood transfusion (148.1±150.7 vs. 23.3±61.1 mL, P<0.001). The VATS group had significantly shorter operative time as compared with the thoracotomy group (94.3±40.9 vs. 133.5±72.1 min, P=0.002). During follow-up, local recurrence was found in 8 (8.7%) patients who underwent thoracotomy, and no significant difference was found in local recurrence rate between the two groups. Four patients who underwent thoracotomy died, and no significant difference was found in mortality between two groups. Conclusions Due to less blood transfusion, shorter operative time and postoperative hospital stay, VATS is a safer surgical treatment for pediatric mediastinal tumors than thoracotomy.
Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial

Abstract Background This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. Methods This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. Results A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. Conclusions After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.
Doxorubicin modulated clock genes and cytokines in macrophages extracted from tumor-bearing mice

ABSTRACT Circadian rhythm is essential for cellular regulation of physiological, metabolic, and immune functions. Perturbations of circadian rhythms have been correlated with increased susceptibility to cancer and poor prognosis in the cancer treatment. Our aim is to investigate the role of doxorubicin (DOX) treatment on clock genes expression and inflammation in intraperitoneal macrophages and the antitumoral response. Methods: Macrophages were extracted from intraperitoneal cavity of mice without or with Lewis lung carcinoma (LLC) and treated with DOX totaling four groups (CTL, LLC, LLC+DOX and DOX) and analyzes of clock genes in six time points (ZT02, ZT06, ZT10, ZT14, ZT18 AND ZT22). Intraperitoneal macrophages cell culture was stimulated with LPS and DOX and clock genes and inflammatory profile were analyzed. In tumor were analyzed macrophages markers. Results: The expression of F4/80 (ZT22) and CD11c (ZT06) tumor tissue was significantly differed between LLC and LCC+DOX groups. In the intraperitoneal macrophages, DOX increased Clock (ZT10), Rev-Erbα (ZT18 and ZT22) and Per2 expressions (ZT18); in the LLC+DOX group was increased Bmal1 (ZT10), Per2 (ZT18) and NF-kB (ZT22) expressions; IL-6 expression increased in the LCC group (ZT02). In intraperitoneal macrophages cell culture stimulated with DOX and LPS after 24 h decreased Clock and Per1. DOX causes depression after 6 and 24 h in TNF-α content and Per2 gene expression after 24 h IL-1β expression was reduced also. Conclusion: DOX treatment in vivo disrupted cytokine and clock genes expression in intraperitoneal macrophages suppressing immune response. Moreover, macrophages cultured with DOX had decreased expression of LPS-stimulated inflammatory cytokines.
Association of BTNL2 single nucleotide polymorphisms with knee osteoarthritis susceptibility.

OBJECTIVE To investigate the association between SNP in the BTNL2 gene region and the susceptibility to osteoarthritis of the knee. METHODS The blood samples of 103 knee osteoarthritis and 134 healthy subjects were collected. Four SNP in the BTNL2 gene region were selected, whole DNA was extracted using the QIAamp blood DNA purification mini reagent, the BTNL2 gene fragment was amplified and sequenced, and the genotype and corresponding frequency were counted. The results were statistically analyzed. RESULTS The four SNP (rs41521946, rs28362677, rs28362678, rs28362675) in the BTNL2 gene region were analyzed using a chi-square test (mutation heterozygote, homozygous, and normal homozygote), and the genotypes of the four mutation points were found to be statistically significant (P=0.003, 0.013, 0.005, and 0.045, respectively). Among the four SNP, the first three SNP were in Hardy-Weinberg equilibrium, and a multivariate logistic regression analysis was used to correlate them with knee osteoarthritis (P=0.003, 0.013, 0.005, respectively). rs28362675 was not in Hardy-Weinberg equilibrium but was associated with knee osteoarthritis (P=0.045), which might be smaller samples or an ethnicity differential allelic variation. The P values of the statistical analysis of age and height in the baseline data of both groups were less than 0.05. Considering the possible impact on the results, they were used as covariates in the analysis. The SNP of rs41521946 and rs28362677 showed a significant change in their associations with mutations, and the genotype P values of rs41521946 (AC+AA)/CC and rs2836267 (AG+AA)/GG were 0.002, 0.006, respectively. CONCLUSION Four SNP (rs41521946, rs28362677, rs28362678, rs28362675) in the BTNL2 gene region were significantly associated with knee osteoarthritis, and the target population might be significantly affected by rs28362675.
Individual identification and individual variability analysis based on cortical folding features in developing infant singletons and twins

Studying the early dynamic development of cortical folding with remarkable individual variability is critical for understanding normal early brain development and related neurodevelopmental disorders. This study focuses on the fingerprinting capability and the individual variability of cortical folding during early brain development. Specifically, we aim to explore (a) whether the developing neonatal cortical folding is unique enough to be considered as a “fingerprint” that can reliably identify an individual within a cohort of infants; (b) which cortical regions manifest more individual variability and thus contribute more for infant identification; (c) whether the infant twins can be distinguished by cortical folding. Hence, for the first time, we conduct infant individual identification and individual variability analysis involving twins based on the developing cortical folding features (mean curvature, average convexity, and sulcal depth) in 472 neonates with 1,141 longitudinal MRI scans. Experimental results show that the infant individual identification achieves 100% accuracy when using the neonatal cortical folding features to predict the identities of 1‐ and 2‐year‐olds. Besides, we observe high identification capability in the high‐order association cortices (i.e., prefrontal, lateral temporal, and inferior parietal regions) and two unimodal cortices (i.e., precentral gyrus and lateral occipital cortex), which largely overlap with the regions encoding remarkable individual variability in cortical folding during the first 2 years. For twins study, we show that even for monozygotic twins with identical genes and similar developmental environments, their cortical folding features are unique enough for accurate individual identification; and in some high‐order association cortices, the differences between monozygotic twin pairs are significantly lower than those between dizygotic twins. This study thus provides important insights into individual identification and individual variability based on cortical folding during infancy.