Miracle-dz/UniFAR-FTUs huggingface dataset:
Three‐dimensional reconstruction of Kambin's triangle based on automated magnetic resonance image segmentation

The three‐dimensional (3D) anatomy of Kambin's triangle is crucial for surgical planning in minimally invasive spine surgery via the transforaminal approach. Few pieces of research have, however, used image segmentation to explore the 3D reconstruction of Kambin's triangle. This study aimed to develop a new method of 3D reconstruction of Kambin's triangle based on automated magnetic resonance image (MRI) segmentation of the lumbar spinal structures. An experienced (>5 years) “ground truth” spinal pain physician meticulously segmented and labeled spinal structures (e.g., bones, dura mater, discs, and nerve roots) on MRI. Subsequently, a 3D U‐Net algorithm was developed for automatically segmenting lumbar spinal structures for the 3D reconstruction of Kambin's triangle. The Dice similarity coefficient (DSC), precision, recall, and the area of Kambin's triangle were used to assess anatomical performance. The automatic segmentation of all spinal structures at the L4/L5 levels and L5/S1 levels resulted in good performance: DSC = 0.878/0.883, precision = 0.889/0.890, recall = 0.873/0.882. Furthermore, the area measurements of Kambin's triangle revealed no significant difference between ground truth and automatic segmentation (p = 0.333 at the L4/L5 level, p = 0.302 at the L5/S1 level). The 3D U‐Net model used in this study performed well in terms of simultaneous segmentation of multi‐class spinal structures (including bones, dura mater, discs, and nerve roots) on MRI, allowing for accurate 3D reconstruction of Kambin's triangle.
Histone methyltransferase WHSC1 loss dampens MHC-I antigen presentation pathway to impair IFN-γ–stimulated antitumor immunity

IFN-γ–stimulated MHC class I (MHC-I) antigen presentation underlies the core of antitumor immunity. However, sustained IFN-γ signaling also enhances the programmed death ligand 1 (PD-L1) checkpoint pathway to dampen antitumor immunity. It remains unclear how these opposing effects of IFN-γ are regulated. Here, we report that loss of the histone dimethyltransferase WHSC1 impaired the antitumor effect of IFN-γ signaling by transcriptional downregulation of the MHC-I machinery without affecting PD-L1 expression in colorectal cancer (CRC) cells. Whsc1 loss promoted tumorigenesis via a non-cell-autonomous mechanism in an Apcmin/+ mouse model, CRC organoids, and xenografts. Mechanistically, we found that the IFN-γ/STAT1 signaling axis stimulated WHSC1 expression and, in turn, that WHSC1 directly interacted with NLRC5 to promote MHC-I gene expression, but not that of PD-L1. Concordantly, silencing Whsc1 diminished MHC-I levels, impaired antitumor immunity, and blunted the effect of immune checkpoint blockade. Patient cohort analysis revealed that WHSC1 expression positively correlated with enhanced MHC-I expression, tumor-infiltrating T cells, and favorable disease outcomes. Together, our findings establish a tumor-suppressive function of WHSC1 that relays IFN-γ signaling to promote antigen presentation on CRC cells and provide a rationale for boosting WHSC1 activity in immunotherapy.
Curcumin regulates the homeostasis of Th17/Treg and improves the composition of gut microbiota in type 2 diabetic mice with colitis

Diabetes mellitus (DM) is one of the most common complications in patients with ulcerative colitis (UC). Curcumin has a wide range of bioactive and pharmacological properties and is commonly used as an adjunct to the treatment of UC and DM. However, the role of curcumin in UC complicated by DM has not been elucidated. Therefore, this study was conducted to construct a model of UC complicating diabetes by inducing UC in DB mice (spontaneously diabetic) with dextran sodium sulfate. In this study, curcumin (100 mg/kg/day) significantly improved the symptoms of diabetes complicated by UC, with a lower insulin level, heavier weight, longer and lighter colons, fewer mucosal ulcers and less inflammatory cell infiltration. Moreover, compared to untreated DB mice with colitis, curcumin‐treated mice showed weaker Th17 responses and stronger Treg responses. In addition, curcumin regulated the diversity and relative abundance of intestinal microbiota in mice with UC complicated by DM at the phylum, class, order, family and genus levels. Collectively, curcumin effectively alleviated colitis in mice with type 2 diabetes mellitus by restoring the homeostasis of Th17/Treg and improving the composition of the intestinal microbiota
Strain evolution and novel downstream processing with integrated catalysis enable highly efficient coproduction of 1,3‐propanediol and organic acid esters from crude glycerol

Bioconversion of natural microorganisms generally results in a mixture of various compounds. Downstream processing (DSP) which only targets a single product often lacks economic competitiveness due to incomplete use of raw material and high cost of waste treatment for by‐products. Here, we show with the efficient microbial conversion of crude glycerol by an artificially evolved strain and how a catalytic conversion strategy can improve the total products yield and process economy of the DSP. Specifically, Clostridium pasteurianum was first adapted to increased concentration of crude glycerol in a novel automatic laboratory evolution system. At m3 scale bioreactor the strain achieved a simultaneous production of 1,3‐propanediol (PDO), acetic and butyric acids at 81.21, 18.72, and 11.09 g/L within only 19 h, respectively, representing the most efficient fermentation of crude glycerol to targeted products. A heterogeneous catalytic step was developed and integrated into the DSP process to obtain high‐value methyl esters from acetic and butyric acids at high yields. The coproduction of the esters also greatly simplified the recovery of PDO. For example, a cosmetic grade PDO (96% PDO) was easily obtained by a simple single‐stage distillation process (with an overall yield more than 77%). This integrated approach provides an industrially attractive route for the simultaneous production of three appealing products from the crude glycerol fermentation broth, which greatly improve the process economy and ecology.
Correlation among cystatin C, homocysteine and arteriosclerosis indexes in patients with chronic kidney disease.

OBJECTIVES Chronic kidney disease (CKD) has become an important public health problem in the world. The occurrence of cardiovascular events is the main cause of death in patients with CKD, and arteriosclerosis is an important pathophysiological basis for cardiovascular diseases. Nowadays, brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) are clinically important indicators to reflect early atherosclerosis. Cystatin C (Cys C)and homocysteine (Hcy) are related to arteriosclerosis in healthy, hypertensive, and diabetic people, while there are few studies on the correlation among Hcy, CysC and arteriosclerosis in patients with CKD. This study aims to investigate the relationship between Cys C, Hcy and atherosclerosis in patients with CKD. METHODS A total of 611 individuals, who met the diagnostic criteria for CKD and underwent physical examination in the Health Management Center of Third Xiangya Hospital, Central South University from June 2019 to June 2020, were selected as the research subjects. Height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured and recorded, and body mass index (BMI) was calculated. Blood samples (5 mL) were collected and Cys C, Hcy, fasting blood glucose (FBG), total cholesterol (TC), serum creatinine (SCr), and other blood indexes were tested. Urine was collected to detect microalbumin and creatinine, and the albumin/creatinine ratio (UACR) was calculated. baPWV and ABI were measured by automatic arteriosclerosis detector. The quartiles of Cys C and Hcy were divided into groups, and the proportion of baPWV and ABI abnormalities among groups was compared pairwise. The correlation between Cys C, Hcy, and baPWV was analyzed by Pearson correlation analysis. Univariate and multivariate logistic regression were used to analyze the effects of Cys C and Hcy on ABI and baPWV. RESULTS Among 611 patients with CKD, 435 (71.19%) had abnormal baPWV and 48 (7.86%) had abnormal ABI. With the increase of Cys C and Hcy levels, the proportion of baPWV and ABI abnormalities were gradually increased. BaPWV was positively correlated with Cys C (r=0.32) and Hcy (r=0.20). After adjusting for confounding factors such as gender, BMI, and FBG, Cys C (OR=6.54, 95% CI 1.93 to 22.14, P<0.01) and Hcy (OR=1.08, 95% CI 1.01 to 1.16, P=0.02) were independent risk factors for abnormal baPWV. Also, after adjusting for confounding factors such as age, sex, BMI, and FBG, Cys C (OR=9.95, 95% CI 2.84 to 34.92, P<0.01) and Hcy (OR=1.06, 95% CI 1.01 to 1.11, P=0.02) were independent risk factors for abnormal ABI. CONCLUSIONS In patients with CKD, baPWV and ABI are significantly correlated with Cys C and Hcy levels. Detection of Cys C and Hcy levels is helpful for the early diagnosis of arteriosclerosis.
Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials

Significance Statement Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. In this systematic review, we summarized evidence from randomized and nonrandomized clinical trials investigating effects of interventions that might attenuate progression of vascular calcification in CKD; interventions were compared with placebo, other comparators, or standard of care. We reviewed 77 heterogeneous clinical trials (63 randomized) involving 6898 participants. Therapy involving magnesium or sodium thiosulfate appears the most promising, with consistent findings of attenuation of vascular calcification progression, but evaluable studies were small and of short duration. Many other studies had inconclusive or conflicting outcomes. This study highlights the need for more definitive trials to evaluate interventions targeting vascular calcification in people with CKD, preferably in association with patient-centered outcomes. Background Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in CKD remain uncertain. Methods We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compared with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3–5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiologic methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method. Results There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E–coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal. Conclusions Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.
A vulnerable residential environment is associated with higher risk of mortality and early transition to permanent residential aged care for community dwelling older South Australians

Abstract Objectives This study examined the impact of the residential environment, measured by the Healthy Ageing/Vulnerable ENvironment (HAVEN) Index, on risk of mortality or entry into Permanent Residential Aged Care (PRAC). Design A retrospective cohort study using data from the Registry of Senior Australians (ROSA) was conducted. HAVEN Index values were matched to the ROSA by residential postcode. Study setting and Participants Older individuals living in metropolitan Adelaide and receiving their first eligibility assessment for aged care services between 2014 and 2016 (N = 16,944). Main Outcome Measure Time to death and entry into PRAC were the main outcomes. Results A higher HAVEN Index value, which represents a favourable residential environment, was associated with a lower risk of mortality and delayed entry to PRAC. For every 0.1 unit increase in HAVEN Index value, the risk of mortality is 3% lower (adjusted hazard ratio [HR], 95% confidence interval [CI] = 0.97, 0.96–0.99) and the risk of entry to PRAC is 5% lower (adjusted subdistribution HR, 95%CI = 0.95, 0.94–0.97) in the first 2 years following aged care assessment. After 2 years, the HAVEN Index was not associated with the risk of transition to PRAC. Conclusion Place-based health inequalities were identified in Australians seeking aged care services, demonstrating that a better understanding of local neighbourhoods may provide insight into addressing ageing inequalities. Spatial indexes, such as the HAVEN Index, are useful tools to identify areas where populations are more vulnerable to adverse health outcomes, informing responses to prioritise local improvements and health interventions to enable healthy ageing.
Deep learning based on biologically interpretable genome representation predicts two types of human adaptation of SARS-CoV-2 variants

Abstract Explosively emerging SARS-CoV-2 variants challenge current nomenclature schemes based on genetic diversity and biological significance. Genomic composition-based machine learning methods have recently performed well in identifying phenotype–genotype relationships. We introduced a framework involving dinucleotide (DNT) composition representation (DCR) to parse the general human adaptation of RNA viruses and applied a three-dimensional convolutional neural network (3D CNN) analysis to learn the human adaptation of other existing coronaviruses (CoVs) and predict the adaptation of SARS-CoV-2 variants of concern (VOCs). A markedly separable, linear DCR distribution was observed in two major genes—receptor-binding glycoprotein and RNA-dependent RNA polymerase (RdRp)—of six families of single-stranded (ssRNA) viruses. Additionally, there was a general host-specific distribution of both the spike proteins and RdRps of CoVs. The 3D CNN based on spike DCR predicted a dominant type II adaptation of most Beta, Delta and Omicron VOCs, with high transmissibility and low pathogenicity. Type I adaptation with opposite transmissibility and pathogenicity was predicted for SARS-CoV-2 Alpha VOCs (77%) and Kappa variants of interest (58%). The identified adaptive determinants included D1118H and A570D mutations and local DNTs. Thus, the 3D CNN model based on DCR features predicts SARS-CoV-2, a major type II human adaptation and is qualified to predict variant adaptation in real time, facilitating the risk-assessment of emerging SARS-CoV-2 variants and COVID-19 control.
Exercise-mediated reinnervation of skeletal muscle in elderly people: An update

Sarcopenia is defined by the loss of muscle mass and function. In aging sarcopenia is due to mild chronic inflammation but also to fiber-intrinsic defects, such as mitochondrial dysfunction. Age-related sarcopenia is associated with physical disability and lowered quality of life. In addition to skeletal muscle, the nervous tissue is also affected in elderly people. With aging, type 2 fast fibers preferentially undergo denervation and are reinnervated by slow-twitch motor neurons. They spread forming new neuro-muscular junctions with the denervated fibers: the result is an increased proportion of slow fibers that group together since they are associated in the same motor unit. Grouping and fiber type shifting are indeed major histological features of aging skeletal muscle. Exercise has been proposed as an intervention for age-related sarcopenia due to its numerous beneficial effects on muscle mechanical and biochemical features. In 2013, a precursor study in humans was published in the European Journal of Translation Myology (formerly known as Basic and Applied Myology), highlighting the occurrence of reinnervation in the musculature of aged, exercise-trained individuals as compared to the matching control. This paper, entitled «Reinnervation of Vastus lateralis is increased significantly in seniors (70-years old) with a lifelong history of high-level exercise», is now being reprinted for the second issue of the «Ejtm Seminal Paper Series». In this short review we discuss those results in the light of the most recent advances confirming the occurrence of exercise-mediated reinnervation, ultimately preserving muscle structure and function in elderly people who exercise.
Prevalence of (Epi)genetic Predisposing Factors in a 5-Year Unselected National Wilms Tumor Cohort: A Comprehensive Clinical and Genomic Characterization

PURPOSE Wilms tumor (WT) is associated with (epi)genetic predisposing factors affecting a growing number of WT predisposing genes and loci, including those causing Beckwith-Wiedemann spectrum (BWSp) or WT1-related syndromes. To guide genetic counseling and testing, we need insight into the prevalence of WT predisposing (epi)genetic factors. PATIENTS AND METHODS All children diagnosed with WT in the Netherlands between 2015 and 2020 were referred to a clinical geneticist. Phenotypic data, disease characteristics, and diagnostic test results were collected. If no genetic predisposition was identified by targeted diagnostic testing, germline (trio-)whole-exome sequencing and BWSp testing on normal kidney-derived DNA were offered. RESULTS A total of 126 cases were analyzed of 128 identified patients. (Epi)genetic predisposing factors were present in 42 of 126 patients (33.3%) on the basis of a molecular diagnosis in blood-derived DNA (n = 26), normal kidney-derived DNA (n = 12), or solely a clinical diagnosis of BWSp (n = 4). Constitutional, heterozygous DIS3L2 variants were identified as a recurrent predisposing factor in five patients (4%), with a second somatic hit in 4 of 5 tumors. Twenty patients (16%) were diagnosed with BWSp while four additional patients without BWSp features harbored chromosome 11p15 methylation defects in normal kidney tissue. Remaining findings included WT1-related syndromes (n = 10), Fanconi anemia (n = 1), neurofibromatosis type 1 (n = 1), and a pathogenic REST variant (n = 1). In addition, (likely) pathogenic variants in adult-onset cancer predisposition genes (BRCA2, PMS2, CHEK2, and MUTYH) were identified in 5 of 56 (8.9%) patients with available whole-exome sequencing data. Several candidate WT predisposition genes were identified, which require further validation. CONCLUSION (Epi)genetic WT predisposing factors, including mosaic aberrations and recurrent heterozygous DIS3L2 variants, were present in at least 33.3% of patients with WT. On the basis of these results, we encourage standard genetic testing after counseling by a clinical geneticist. In this study, a 5-year Dutch national cohort of children with Wilms tumor (WT) was referred for genetic evaluation, aiming to determine the prevalence and distribution of (epi)genetic predisposing factors. If no genetic predisposition was identified by targeted diagnostic testing, (trio-) whole exome sequencing was offered. (Epi)genetic predisposing factors, including mosaic aberrations, were found to be present in 33.3% of the patients. We identified an important role for constitutional heterozygous DIS3L2 variants. Based on these results, standard genetic testing after counseling by a clinical geneticist is encouraged for all children with WT.
A Meta-Analysis of the Effects of Childhood Maltreatment on Elderly Depression

Background: The present study aimed to synthesize the effects of five types of child maltreatment (physical abuse, emotional abuse, sexual abuse, physical neglect and emotional neglect) on late-life depression. Method: Four English-language databases (Web of Science, PsycINFO and PsycARTICLES, PubMed, and Cochrane Library) and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Weipu Database) were systematically reviewed, and data related to the association between child maltreatment and late-life depression were extracted. Ten studies involving 30,308 older adults were included, and the effect sizes were pooled using random-effect models. Findings: Except for sexual abuse, four types of child maltreatment were found to be positively associated with late-life depression. Physical abuse, emotional abuse and physical neglect were associated with elderly depression (PA: OR = 1.73, 95% CI = 1.55–1.95, p < .001; EA: OR = 1.92, 95% CI = 1.73–2.12, p < .001; PN: OR = 2.05, 95% CI = 1.15–3.67, p < .01) at a small level, and emotional neglect was associated with elderly depression (OR = 3.25, 95% CI = 1.43–7.39, p < .001) at an approximately moderate level. Gender moderated the relationship between physical neglect, emotional neglect, and late-life depression. Conclusion: Our findings highlight the significance of child maltreatment in the development of late-life depression, and underscore the need for future research and practice to explore potential ways to address late-life depression among older adults who suffered child maltreatment.
Prozess zur Implementierung Evidenzbasierter Parenteraler Ernährung in Deutschen Perinatalzentren – Ergebnisse eines Multidisziplinären Netzwerks

Zusammenfassung Einleitung Die parenterale Ernährung (PE) ist gewöhnlich bei Frühgeborenen<1500 g Geburtsgewicht und kranken Neugeborenen indiziert und gewährleistet eine Versorgung mit essentiellen Nährstoffen. Da ein hohes Maß Therapiesicherheit erforderlich ist, gibt die europäische Leitlinie Empfehlungen zur sicheren Anwendung. Dieses Projekt zielte darauf ab, die Anwendung der europäischen Leitlinie in deutschen Perinatalzentren zu evaluieren und Barrieren, die die Umsetzung erschweren oder verhindern, abzubilden. Zusätzlich sollten Lösungsansätze zur Überwindung möglicher Barrieren erarbeitet werden. Methodik und Ergebnisse In einer multidisziplinären Kooperation wurde eine Online-Umfrage durchgeführt, in der PädiaterInnen und KrankenhausapothekerInnen aus Perinatalzentren zur Umsetzung der europäischen Leitlinien befragt wurden. Die Umfrageergebnisse wiesen auf Barrieren entlang des Bereitstellungsprozesses der PE hin, die eine leitliniengerechte Anwendung erschweren. Basierend auf den Ergebnissen erarbeitete das Expertennetzwerk ein interaktives Toolkit mit vereinfachten Leitlinienempfehlungen, leitlinienkonformen Anwendungsratschlägen, Best-Practice-Beispielen, Formularen und Handouts. Es soll zur kritischen Reflexion der Routineprozesse anregen und liefert konkrete Lösungsansätze zur Überwindung der Barrieren in der Praxis. Schlussfolgerung Die Anwendung der PE bei Früh- und kranken Neugeborenen weicht von den Leitlinienempfehlungen ab. Das erarbeitete Toolkit liefert praxisorientiere Hilfestellungen mit dem Ziel, eine leitliniengerechte Anwendung in Perinatalzentren zu fördern.