Miracle-dz/UniFAR-FTUs huggingface dataset:
Recapitulating bone development through engineered mesenchymal condensations and mechanical cues for tissue regeneration

Mechanical loading regulates mesenchymal condensation–mediated endochondral bone regeneration. Taking cues from development One way that bone forms during development is termed endochondral ossification, a process requiring a cartilage intermediate. McDermott et al. mimicked this process during bone defect repair in rats, implanting cylindrical constructs of human mesenchymal stem cells and transforming growth factor–β1 into critical-sized femur defects and using fixation plates to apply mechanical loading. Loading altered cartilage persistence, blood vessel formation, and bone regeneration. Applying mechanical forces 4 weeks after construct implantation resulted in better bone bridging than loading at the time of implantation. This study demonstrates how mechanical loading can be used with tissue engineering to augment bone regeneration. Large bone defects cannot form a callus and exhibit high complication rates even with the best treatment strategies available. Tissue engineering approaches often use scaffolds designed to match the properties of mature bone. However, natural fracture healing is most efficient when it recapitulates development, forming bone via a cartilage intermediate (endochondral ossification). Because mechanical forces are critical for proper endochondral bone development and fracture repair, we hypothesized that recapitulating developmental mechanical forces would be essential for large bone defect regeneration in rats. Here, we engineered mesenchymal condensations that mimic the cellular organization and lineage progression of the early limb bud in response to local transforming growth factor–β1 presentation from incorporated gelatin microspheres. We then controlled mechanical loading in vivo by dynamically tuning fixator compliance. Mechanical loading enhanced mesenchymal condensation–induced endochondral bone formation in vivo, restoring functional bone properties when load initiation was delayed to week 4 after defect formation. Live cell transplantation produced zonal human cartilage and primary spongiosa mimetic of the native growth plate, whereas condensation devitalization before transplantation abrogated bone formation. Mechanical loading induced regeneration comparable to high-dose bone morphogenetic protein-2 delivery, but without heterotopic bone formation and with order-of-magnitude greater mechanosensitivity. In vitro, mechanical loading promoted chondrogenesis and up-regulated pericellular matrix deposition and angiogenic gene expression. In vivo, mechanical loading regulated cartilage formation and neovascular invasion, dependent on load timing. This study establishes mechanical cues as key regulators of endochondral bone defect regeneration and provides a paradigm for recapitulating developmental programs for tissue engineering.
Classification and Prediction of atherosclerosis diseases using machine learning algorithms

atherosclerosis disease is the major reason that increases the mortality rate around the world. This ailment diagnosis becomes difficult due to the inattention of initial symptoms. Thus, there is a need to improve the prediction accuracy of cardiovascular diseases in order to minimize treatment costs and to avoid critical cases. This contribution is articulated to define a medical decision support system (MDSS) of atherosclerosis disease. This system is able to give heart disease prediction using the patient's clinical data. This MDSS is based on machine learning techniques such as K-medoids and k-means clustering for classification, Artificial Neural Network (ANN) and K-Nearest Neighbor (KNN) for prediction the presence and the absence of Atherosclerosis disease. The system is validated on the Cleveland heart diseases database. This data is split into training and testing data with 13 features for each patient. We evaluated the proposed system using many similarity measures such as Matthews’s correlation coefficient (MCC). We reached 96% accuracy and 0.92 MCC, significantly outperforms currently published research.
Pregnancy and Family Planning in Multiple Sclerosis.

PURPOSE OF REVIEW This article provides practical guidance on successful management of women with multiple sclerosis (MS) through pregnancy and the postpartum period. RECENT FINDINGS Recent studies indicate that most women diagnosed with MS today can have children, breast-feed, and resume beta interferons or glatiramer acetate per their preferences without incurring an increased risk of relapses during the postpartum period. More than 40% of women with mild MS do not require any treatment before conception or in the postpartum period. Women with highly active MS can now become well-controlled before, throughout, and after pregnancy via highly effective treatments. Unfortunately, pregnancy does not protect against relapses following the cessation of fingolimod or natalizumab, and some women experience severe rebound relapses during pregnancy. Accidental first-trimester exposure to teriflunomide or fingolimod increases the risk of fetal harm. SUMMARY Most women with MS can have normal pregnancies and breast-feed without incurring harm. Clinicians should avoid prescribing medications with known teratogenic potential (teriflunomide, fingolimod), known risk of severe rebound relapses (fingolimod, natalizumab), or unclear but plausible risks (dimethyl fumarate, alemtuzumab) to women of childbearing age who desire pregnancy or are not on reliable birth control. If a treatment needs to be resumed during breast-feeding, clinicians should opt for glatiramer acetate, interferon beta, natalizumab, or rituximab/ocrelizumab, as biologically plausible risks to the infant are exceedingly low.
Relative Contributions of Bone Density, Bone Turnover, and Clinical Risk Factors to Long‐Term Fracture Prediction

Long‐term fracture prediction using bone mineral density remains controversial, as does the additional contribution from assessing bone turnover or clinical risk factors. We measured bone mineral density at various sites, along with biochemical markers of bone turnover, sex steroid levels, and over 100 clinical variables, at baseline on an age‐stratified sample of 304 Rochester, MN women in 1980. The 225 postmenopausal women were subsequently followed for 3146 person‐years (median, 16.2 years per subject), wherein they experienced 302 new fractures: 81% resulted from minimal or moderate trauma and 60% of these involved the proximal femur, thoracic or lumbar vertebrae, or distal forearm. Accounting for multiple fractures per subject, these osteoporotic fractures together were best predicted by baseline femoral neck bone mineral density (age‐adjusted hazard ratio [HR] per SD decrease, 1.37; 95% CI, 1.10–1.70); 19 moderate trauma forearm fractures were best predicted by distal radius bone mineral content, whereas 28 hip fractures and 100 vertebral fractures were best predicted by femoral neck bone mineral density. Femoral neck bone mineral density performed comparably in predicting osteoporotic fracture risk within the first decade of follow‐up (HR, 1.38; 95% CI, 1.10–1.74) as well as more than 10 years after baseline (HR, 1.39; 95% CI, 1.05–1.84). The older biochemical markers were not associated with fractures, but serum “free” estradiol index was independently predictive of short‐ and long‐term fracture risk. Consistent clinical risk factors were not identified, but statistical power was limited. Identifying patients at increased long‐term risk of fracture is challenging, but it is reassuring that femoral neck bone mineral density can predict osteoporotic fractures up to 20 years later.
Perceived Weight Discrimination Mediates the Prospective Association Between Obesity and Physiological Dysregulation: Evidence From a Population-Based Cohort

Obesity is thought to cause ill health because of the biological strain that excess fat has on physiological function. We tested an alternative explanation in a population-based sample of 3,609 older English adults—that the pervasive discrimination experienced by individuals with excess weight may in part explain why obesity is associated with subsequent multisystem physiological dysregulation, measured via clinical indicators of cardiovascular, metabolic, and immune function. We found that both obesity and perceived weight discrimination predicted an increase in physiological dysregulation from baseline to follow-up 4 years later. Perceived discrimination because of body weight experienced by individuals with obesity explained more than one quarter of the prospective association between obesity and a deterioration in biomarkers of health status. These findings highlight the possibility that the stigma experienced by individuals with obesity may play an important role in explaining the obesity-related disease burden.
Distance to trauma centres among gunshot wound victims: identifying trauma ‘deserts’ and ‘oases’ in Detroit

Introduction Among the factors related to survival among individuals with gun shot wounds (GSW) is distance to trauma care. Relatively little is known about neighbourhood-level patterns of GSW mortality and distance to hospitals with trauma centres. This study focuses on distance to the nearest trauma centre as a correlate of survival among GSW victims. Methods Fatal and non-fatal shooting incident data for 9,205 victimisation in Detroit, Michigan between 2011 and 2017 were collected. A Bayesian conditional autoregressive model was utilised to estimate block-group levels of GSW mortality. Clustering techniques were used to identify spatially proximate neighbourhoods with higher or lower than expected rates of GSW mortality. Results Distance to the nearest trauma centre was associated with a 22% increase in fatal outcomes, per-mile (OR 1.22, 95% CI, 1.06 to 1.40) after adjusting for block-group level covariates. A Getis-Ord Gi* analysis identified 91 block groups with lower than expected rates of GSW mortality and 12 block-groups with higher than expected rates. Conclusion Distance to the nearest trauma centre is associated with GSW victim survival. Clusters of block-groups with below-average GSW mortality were observed within close proximity of major trauma centres in Detroit. Improving speed and access to trauma care may play a role in reducing GSW mortality.
The dual lifestyle of genome‐integrating virophages in protists

DNA viruses with efficient host genome integration capability were unknown in eukaryotes until recently. The discovery of virophages, satellite‐like DNA viruses that depend on lytic giant viruses that infect protists, revealed a genetically diverse group of viruses with high genome mobility. Virophages can act as strong inhibitors of their associated giant viruses, and the resulting beneficial effects on their unicellular hosts resemble a population‐based antiviral defense mechanism. By comparing various aspects of genome‐integrating virophages, in particular the virophage mavirus, with other mobile genetic elements and parasite‐derived defense mechanisms in eukaryotes and prokaryotes, we show that virophages share many features with other host–parasite systems. Yet, the dual lifestyle exhibited by mavirus remains unprecedented among eukaryotic DNA viruses, with potentially far‐reaching ecological and evolutionary consequences for the host.
Set Relations in Social Research: Evaluating Their Consistency and Coverage

Because of its inherently asymmetric nature, set-theoretic analysis offers many interesting contrasts with analysis based on correlations. Until recently, however, social scientists have been slow to embrace set-theoretic approaches. The perception was that this type of analysis is restricted to primitive, binary variables and that it has little or no tolerance for error. With the advent of “fuzzy” sets and the recognition that even rough set-theoretic relations are relevant to theory, these old barriers have crumbled. This paper advances the set-theoretic approach by presenting simple descriptive measures that can be used to evaluate set-theoretic relationships, especially relations between fuzzy sets. The first measure, “consistency,” assesses the degree to which a subset relation has been approximated, whereas the second measure, “coverage,” assesses the empirical relevance of a consistent subset. This paper demonstrates further that set-theoretic coverage can be partitioned in a manner somewhat analogous to the partitioning of explained variation in multiple regression analysis.
Gene therapy for rheumatoid arthritis

Rheumatoid arthritis (RA) is a disabling, painful disorder affecting 1% of the world’s population. Although the aetiology of RA remains unknown, recent advances in understanding its pathophysiology have led to the characterisation of several proteins whose activities may be anti-arthritic. Clinical application of such proteins has greatly improved the treatment of RA, but the disease remains incurable and difficult to manage in a substantial number of patients. Thus, there are continued efforts to develop new therapeutic strategies. Because RA is a chronic condition, effective treatment will probably require the presence of therapeutic agents for extended periods of time. In the case of proteins, this is problematic. Gene therapy may offer a solution to this problem. Experimental studies have confirmed the feasibility, efficacy and safety of gene therapy for the treatment of animal models of arthritis. Several different approaches have shown promise in this regard, including gene transfer to the synovial lining cells of individual joints and the systemic delivery of genes to extra-articular locations. One unexpected finding has been the ‘contralateral effect’ in which gene delivery to one joint of an animal with polyarticular disease leads to improvement of multiple joints. Investigation of this phenomenon has led to interest in cell trafficking and the genetic modification of antigen-presenting cells (APC). The first Phase I clinical trial tested the feasibility and safety of ex vivo gene transfer to the synovial lining of human joints. This clinical trial has been successfully completed and two other Phase I trials are in progress. A Phase II study is now being planned to investigate the efficacy of gene transfer to the joints of patients with early stage RA.
The Developmental Phases of Zebrafish Myogenesis

The development and growth of vertebrate axial muscle have been studied for decades at both the descriptive and molecular level. The zebrafish has provided an attractive model system for investigating both muscle patterning and growth due to its simple axial musculature with spatially separated fibre types, which contrasts to complex muscle groups often deployed in amniotes. In recent years, new findings have reshaped previous concepts that define how final teleost muscle form is established and maintained. Here, we summarise recent findings in zebrafish embryonic myogenesis with a focus on fibre type specification, followed by an examination of the molecular mechanisms that control muscle growth with emphasis on the role of the dermomyotome-like external cell layer. We also consider these data sets in a comparative context to gain insight into the evolution of axial myogenic patterning systems within the vertebrate lineage.
Epidemiological Trends and Resistance Associated with Stenotrophomonas maltophilia Bacteremia: A 10-Year Retrospective Cohort Study in a Tertiary-Care Hospital in Hungary

Stenotrophomonas maltophilia has been recognized as an emerging nosocomial pathogen in invasive infections of immunocompromised, severely debilitated patients with significant underlying illnesses. The first-choice drug in these infections is sulfamethoxazole-trimethoprim (SMX/TMP), and resistance to this antimicrobial is a daunting challenge for clinicians. The aim of this study was to assess the prevalence of S. maltophilia bacteremia and SMX/TMP-resistance levels at a tertiary-care university hospital. A total of 175 episodes of S. maltophilia bacteremia were identified (2008–2012: n = 82, 2013–2017: n = 93; p = 0.061), 52% of affected patients were 60 years of age, and had recent surgery, severe injuries or underlying conditions (malignant hematologic diseases and solid tumors) in their history. Sixteen percent of isolates were resistant to SMX/TMP (2008–2012: n = 13.8%, 2013–2017: n = 17.2%; p = 0.076), and out of the resistant strains, 32.7% were also resistant to levofloxacin and colistin. Our findings on the SMX/TMP-resistance were similar to global literature data.
CD4 T Cell Depletion at the Cervix during HIV Infection Is Associated with Accumulation of Terminally Differentiated T Cells

ABSTRACT In blood, the accumulation of terminally differentiated (TD) T cells during HIV infection is associated with CD4 T cell loss and HIV disease progression. Here, we investigated the maintenance and functional characteristics of memory T cells at the cervix. We found that CD4 T cell depletion at the cervix mirrors CD4 depletion in blood. In all women, depletion of CD4 T cells at the cervix was associated with significant reductions in CD45RA− CCR7+ (central memory [CM]) T cells and the accumulation of CD45RA+ CCR7− (TD T cells). We determined whether inflammation in the genital tract was associated with the local differentiation of T cells at the cervix. In uninfected women, genital tract inflammation was associated with the accumulation of CD45RA− CCR7+ CM CD4 T cells and reduced frequencies of CD45RA+ CCR7− TD cells at the cervix. This finding may reflect the fact that, in the absence of HIV infection, TD T cells may be slowly lost in the presence of genital inflammation, while CD45RA− CCR7+ CM T cells are recruited to replenish the diminishing CD4 T cell pool. Following global stimulation with phorbol myristate acetate (PMA)-ionomycin, we noted a significant interleukin 2 (IL-2) deficit in both cervical and blood CD4 T cells from HIV-infected women compared to uninfected women, while gamma interferon (IFN-γ) production was similar, irrespective of HIV status. Few HIV-infected women had detectable IFN-γ and IL-2 HIV-specific T cell responses at the cervix, and these responses were significantly lower in magnitude than the corresponding responses in blood. These data suggest that CD4 depletion was associated with the accumulation of terminally differentiated T cell phenotypes at the cervical mucosa defective in their ability to produce IL-2. CD4 depletion and compromised immunity at the cervix may be accompanied by progressive decline of central memory-like T cells and development of T cells toward terminally differentiated phenotypes.
The Complement Receptor C5aR2: A Powerful Modulator of Innate and Adaptive Immunity

Complement activation generates the core effector protein C5a, a potent immune molecule that is linked to multiple inflammatory diseases. Two C5a receptors, C5aR1 (C5aR, CD88) and C5aR2 (C5L2, GPR77), mediate the biological activities of C5a. Although C5aR1 has broadly acknowledged proinflammatory roles, C5aR2 remains at the center of controversy, with existing findings supporting both immune-activating and immune-dampening functions. Recent progress has been made toward resolving these issues. Instead of being a pure recycler and sequester of C5a, C5aR2 is capable of mediating its own set of signaling events and through these events exerting significant immunomodulatory effects not only toward C5aR1 but also other pattern recognition receptors and innate immune systems, such as NLRP3 inflammasomes. This review highlights the existing knowns and unknowns concerning C5aR2 and provides a timely update on recent breakthroughs which are expected to have a substantial impact on future fundamental and translational C5aR2 research.
Occipital Mega Encephalocele Associated with Acute Inflammation

scopically, yellow-green-colored granular tissue examination showed patchy, dense polymorphonuclear neutrophil infiltration. The baby had no more problems and was discharged from the hospital. At follow-up, the neurological examination was normal, and no abnormal increase in the head circumference was observed. Almost 70% of the encephaloceles occur in the occipital region and are most commonly located in close proxA 4-hour-old newborn was referred to our hospital because of a large sac at the back of the head ( fig. 1 ). The past medical history revealed no pathology for the antenatal period. At physical examination, the head circumference was 33 cm, and both fontanels were pulsatile but not tense. A 25 ! 30 ! 20-cm liquid-filled, large sac originating around the external occipital protuberance was present. The sac was soft, fluctuant, and translucence, and its walls were intact. A computed tomography scan showed a bone defect at the occipital region and neural structures related to inflammatory areas, including hypodense areas. The ventricular system was within normal limits. The sac was excised and the defect repaired. Macroscopically, in the inner surface of the sac, highly vascularized, congested, yellow-green-colored, granular, fragile atypical tissue was seen ( fig. 2 ). A control cranial computed tomography scan showed dilations at third and lateral ventricles. A right ventriculoperitoneal shunt was placed. Cranial magnetic resonance imaging revealed corpus callosum dysgenesis. Microscopic examination of resected tissues revealed keratinized multilayered squamous tissue beneath the epithelia, covered with ectatic, congestive vascular proliferation extending to the deep layers, and neural tissue at the deep layers ( fig. 3 a). Microscopic examination of the green-yellow-colored granular tissues revealed dense microcystic areas containing polymorphonuclear leukocytes ( fig. 3 b). Macro-
β‐Adrenoceptor signaling regulates proliferation and contraction of human bladder smooth muscle cells under pathological hydrostatic pressure

Partial bladder outlet obstruction (PBOO) promotes bladder detrusor hyperplasia, increases bladder pressure, and decreases bladder compliance. To extensively explore its underlying mechanism, our study aimed to investigate the effect of pathological hydrostatic pressure on human bladder smooth muscle cell (hBSMC) proliferation and contraction through β‐adrenoceptor (ADRB) signaling in vitro.
Genome-Wide Profiling of the Microrna Transcriptome Regulatory Network to Identify Putative Candidate Genes Associated with Backfat Deposition in Pigs

Simple Summary Backfat thickness is an important characteristic in pig breeding. In this study, the key microRNAs (miRNAs) and genes associated with pig backfat deposition were detected and characterized using RNA sequencing between adipose tissues of high-backfat and low-backfat pigs. Strong candidate mRNA‒miRNA interaction pairs were identified to affect backfat deposition through the regulation of target genes by miRNAs. These results provide novel insights into the backfat deposition mechanism in pigs. Abstract Backfat deposition is strongly related to carcass traits, growth rate, feed conversion rate, and reproductive performance in pig production. To understand the molecular mechanisms underlying porcine backfat thickness phenotypes, transcriptome and miRNA profiling of backfat from high-backfat thickness and low-backfat thickness pigs were performed by RNA sequencing. Twenty genes encoding for miRNAs and 126 genes encoding for protein-coding genes were found to be differentially expressed between the two libraries. After integrative analysis of DEMs targets and DEGs, a total of 33 mRNA‒miRNA interaction pairs were identified, and the regulatory networks of these pairs were determined. Among these genes, five (AQP9, DKK3, GLYCTK, GLIPR1, and DUSP2) related to fat deposition were found to be strong candidate genes, and mir-31-5p/AQP9 and mir-31-5p/GLIPR1 may play important roles in fat deposition. Additionally, potential adipogenesis-related genes and miRNAs were identified. These findings improve the current understanding of the molecular genetic mechanisms of subcutaneous fat deposition in pigs and provide a foundation for further studies.