Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemical Analysis of CYP11B2, CYP11B1 and β-catenin Helps Subtyping and Relates With Clinical Characteristics of Unilateral Primary Aldosteronism

Background: Primary aldosteronism is caused by aldosterone overproduction. While conventional hematoxylin-eosin staining can demonstrate morphological abnormality, it cannot provide any functional histopathological information. We aimed to identify the diagnostic, functional and prognostic value of CYP11B2, CYP11B1, and β-catenin immunostaining in unilateral hyperaldosteronism. Method: A total of 134 patients with unilateral hyperaldosteronism were recruited in our study. The expression of CYP11B2, CYP11B1, and β-catenin was evaluated semiquantitatively on 134 patients’ sections using immunohistochemistry technology and the relationship with clinical data was assessed. Results: Patients were classified into four subtypes based on CYP11B2 staining as below: (1)118 patients with unilateral single aldosterone-producing adenoma (APA), (2)11 with unilateral multiple APA, (3)four with aldosterone-producing cell cluster (APCC), and (4)one with an undefined source. Adjusted CYP11B2 H-score was correlated with serum aldosterone, aldosterone to renin ratio (ARR), and serum potassium. In the abnormal β-catenin staining group, hypertension duration, aldosterone, ARR, cortisol, tumor diameter, tumor area, and CYP11B2 H-score were significantly higher than those of the wild-type group. Serum potassium level was significantly lower in the abnormal β-catenin staining group. Age, gender, BMI, family history of hypertension, adjusted CYP11B2 and CYP11B1 H-scores differed significantly between complete clinical success and incomplete clinical success groups. Age, gender and family history of hypertension were independently associated with complete clinical success based on multivariate logistic regression analysis. Conclusion: CYP11B2 immunostaining could improve the differential diagnosis of unilateral hyperaldosteronism. Adjusted CYP11B2 H-score could be used as a histopathological marker to reflect the severity of unilateral APA. Dysregulation of Wnt/β-catenin signaling and impaired β-catenin degradation may provoke the proliferation and enhance the steroidogenic ability of APA tumor cells, indicating that the Wnt pathway might be a potential, actionable, therapeutic target in the treatment of hyperaldosteronism. Age, sex and family history of hypertension were independent predictors of clinical outcome after adrenalectomy for unilateral hyperaldosteronism.
In-House, Open-Source 3D-Software-Based, CAD/CAM-Planned Mandibular Reconstructions in 20 Consecutive Free Fibula Flap Cases: An Explorative Cross-Sectional Study With Three-Dimensional Performance Analysis

Background Mandibular reconstruction is conventionally performed freehand, CAD/CAM-assisted, or by using partially adjustable resection aids. CAD/CAM-assisted reconstructions are usually done in cooperation with osteosynthesis manufacturers, which entails additional costs and longer lead time. The purpose of this study is to analyze an in-house, open-source software-based solution for virtual planning. Methods and Materials All consecutive cases between January 2019 and April 2021 that underwent in-house, software-based (Blender) mandibular reconstruction with a free fibula flap (FFF) were included in this cross-sectional study. The pre- and postoperative Digital Imaging and Com munications in Medicine (DICOM) data were converted to standard tessellation language (STL) files. In addition to documenting general information (sex, age, indication for surgery, extent of resection, number of segments, duration of surgery, and ischemia time), conventional measurements and three-dimensional analysis methods (root mean square error [RMSE], mean surface distance [MSD], and Hausdorff distance [HD]) were used. Results Twenty consecutive cases were enrolled. Three-dimensional analysis of preoperative and virtually planned neomandibula models was associated with a median RMSE of 1.4 (0.4–7.2), MSD of 0.3 (-0.1–2.9), and HD of 0.7 (0.1–3.1). Three-dimensional comparison of preoperative and postoperative models showed a median RMSE of 2.2 (1.5–11.1), MSD of 0.5 (-0.6–6.1), and HD of 1.5 (1.1–6.5) and the differences were significantly different for RMSE (p < 0.001) and HD (p < 0.001). The difference was not significantly different for MSD (p = 0.554). Three-dimensional analysis of virtual and postoperative models had a median RMSE of 2.3 (1.3–10.7), MSD of -0.1 (-1.0–5.6), and HD of 1.7 (0.1–5.9). Conclusions Open-source software-based in-house planning is a feasible, inexpensive, and fast method that enables accurate reconstructions. Additionally, it is excellent for teaching purposes.
Editorial: Tau Pathology in Neurological Disorders

Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada, Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, United Kingdom, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada, Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada, Department of Pharmacology, Oxford University, Oxford, United Kingdom
Clinical Characteristics of Pediatric Cases of COVID-19 in Hunan, China: A Retrospective, Multi-Center Case Series

Objective: Aimed to investigate the epidemiological characteristics, clinical features, treatment, and short-term prognosis of COVID-19 in children. Methods: Retrospective analysis was conducted in 48 children with COVID-19 admitted to 12 hospitals in eight cities in Hunan province, China, from January 26, 2020 to June 30, 2020. Results: Of the 48 cases, Familial clusters were confirmed for 46 children (96%). 16 (33%) were imported from other provinces. There were 11 (23%) asymptomatic cases. only 2 cases (4%) were severe. The most common symptom was fever (n = 20, 42%). Other symptoms included cough (n = 19, 40%), fatigue (n = 8, 17%), and diarrhea (n = 5, 10%). In the early stage, the total peripheral blood leukocytes count increased in 3(6%) cases and the lymphocytes count decreased in 5 (10%) cases. C-reactive protein and procalcitonin were elevated respectively in 3 (6%) cases and 2 (4%) cases. There were abnormal chest CT changes in 22 (46%) children, including 15 (68%) with patchy ground glass opacity, 5 (22%) with consolidation, and 2 (10%) with mixed shadowing. In addition to supportive treatment, antiviral therapy was received by 41 (85%) children, 11 (23%) patients were treated with antibiotics, and 2 (4%) were treated with methylprednisolone and intravenous immunoglobulin. Compared to 2 weeks follow-up, one child developed low fever and headache during the 4 weeks follow-up, 3 (6%) children had runny noses, one of them got mild cough, and 4 (12%) children had elevated white blood cells and lymphocytes. However, LDH and CK increased at 2 weeks and 4 weeks follow-up. 2 weeks follow-up identified normal chest radiographs in 33 (69%) pediatric patients. RT-PCR detection of SARS-CoV-2 was negative in all follow-up patients at 2 and 4 weeks follow-up. All 48 pediatric patients were visited by calling after 1 year of discharge. Conclusions: Most cases of COVID-19 in children in Hunan province were asymptomatic, mild, or moderate. Close family contact was the main route of infection. It appeared that the younger the patient, the less obvious their symptoms. Epidemiological history, nucleic acid test, and chest imaging were important tools for diagnosis in children.
Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) has poor prognosis with limited treatment options, with little therapeutic progress made during the past several decades. DNA damage response (DDR) associated therapies, including radiation and inhibitors of DDR, demonstrate potential efficacy against TNBC, especially under the guidance of genomic subtype-directed treatment. The tumor immune microenvironment also contributes greatly to TNBC malignancy and response to conventional and targeted therapies. Immunotherapy represents a developing trend in targeted therapies directed against TNBC and strategies combining immunotherapy and modulators of the DDR pathways are being pursued. There is increasing understanding of the potential interplay between DDR pathways and immune-associated signaling. As such, the question of how we treat TNBC regarding novel immuno-molecular strategies is continually evolving. In this review, we explore the current and upcoming treatment options of TNBC in the context of DNA repair mechanisms and immune-based therapies, with a focus on implications of recent genomic analyses and clinical trial findings.
Steering Mast Cells or Their Mediators as a Prospective Novel Therapeutic Approach for the Treatment of Hematological Malignancies

Tumor cells require signaling and close interaction with their microenvironment for their survival and proliferation. In the recent years, Mast cells have earned a greater importance for their presence and role in cancers. It is known that mast cells are attracted towards tumor microenvironment by secreted soluble chemotactic factors. Mast cells seem to exert a pro-tumorigenic role in hematological malignancies with a few exceptions where they showed anti-cancerous role. This dual role of mast cells in tumor growth and survival may be dependent on the intrinsic characteristics of the particular tumor, differences in tumor microenvironment according to tumor type, and the interactions and heterogeneity of mediators released by mast cells in the tumor microenvironment. In many studies, Mast cells and their mediators have been shown to affect tumor survival and growth, prognosis, inflammation, tumor vascularization and angiogenesis. Modulating mast cell accumulation, viability, activity and mediator release patterns may thus be important in controlling these malignancies. In this review, we emphasize on the role of mast cells in lymphoid malignancies and discuss strategies for targeting and steering mast cells or their mediators as a potential therapeutic approach for the treatment of these malignancies.
Prognostic Significance of Admission Systemic Inflammation Response Index in Patients With Spontaneous Intracerebral Hemorrhage: A Propensity Score Matching Analysis

Intracerebral hemorrhage (ICH) accounts for ~15% of all strokes and is associated with high mortality and disability rates. The systemic inflammation response index (SIRI) is a novel systemic inflammatory marker based on peripheral neutrophil, monocyte, and lymphocyte counts. This study aimed to evaluate the prognostic significance of admission SIRI in patients with spontaneous ICH and compare its predictive ability with that of the neutrophil-to-lymphocyte ratio (NLR). This retrospective study was conducted based on a prospectively collected database of patients with ICH between June 2016 and January 2019. Propensity score matching (PSM) was conducted to adjust for potential imbalances in the clinical parameters. A total of 403 patients were included in the original cohort. The optimal SIRI cut-off value was 2.76. After 1:1 PSM based on potential confounding variables, a new cohort containing 262 patients was established for further analysis. In the original cohort, SIRI served as an independent predictor of 3-month functional outcome [odds ratio (OR), 1.302; 95% CI, 1.120–1.512; p = 0.001] and 1-month mortality (OR, 1.072; 95% CI, 1.020–1.126; p = 0.006), while NLR was independently associated with only 3-month functional outcomes (OR, 1.051; 95% CI, 1.004–1.100; p = 0.031) and not 1-month mortality. The same applied to the PSM cohort. Receiver operating characteristic analyses and predictive models indicated that in most instances, SIRI was superior to NLR and their components in predicting the outcomes of patients with ICH. Our study found that SIRI is determined to be an independent predictive indicator for ICH patients in 3-month functional outcomes and 1-month mortality. The prognostic predictive ability of SIRI was stronger than that of NLR.
Diagnostic and Therapeutic Maneuvers for Anterior Canal BPPV Canalithiasis: Three-Dimensional Simulations

Background and Objectives: Anterior canal BPPV is a rare BPPV variant. Various diagnostic and therapeutic maneuvers have been described for its management. The aim of this study was to use three-dimensional simulation models to visualize otoconial debris movement within the anterior canal during diagnostic tests and different liberatory maneuvers. This can help to optimize existing treatment maneuvers and help in the development of better management protocols. Methods: Based on reconstructed MRI images and fluid dynamics, a 3D dynamic simulation model (as a function of time) was developed and applied. Simulations of the supine head-hanging test for diagnosis of ac-BPPV were studied. Three repositioning maneuvers were simulated: 1) the Yacovino maneuver and its modifications, 2) the reverse Epley maneuver and 3) the short canal repositioning (CRP) maneuver. Results: The simulation showed that the supine head-hanging test is a good test for diagnosis of ac-BPPV affecting both labyrinths and demonstrated why there is no inversion of nystagmus on sitting up. The Yacovino maneuver was seen to be an effective treatment option for ac-BPPV without having to determine the side involved. However, simulations showed that the classical Yacovino maneuver carried a risk of canal switch to the posterior canal. To overcome this risk, a modified Yacovino maneuver is suggested. The reverse Epley maneuver was not an effective treatment. Short CRP is useful in ac-BPPV treatment; however, it requires determination of side of involvement. Conclusion: The 3D simulator of the movement of the otoconial debris presented here can be used to test the mechanism of action and the theoretical efficacy of existing diagnostic tests and maneuvers as well as to develop new treatment maneuvers to optimize BPPV treatment.
Predicting Blood Concentration of Tacrolimus in Patients With Autoimmune Diseases Using Machine Learning Techniques Based on Real-World Evidence

Tacrolimus is a widely used immunosuppressive drug in patients with autoimmune diseases. It has a narrow therapeutic window, thus requiring therapeutic drug monitoring (TDM) to guide the clinical regimen. This study included 193 cases of tacrolimus TDM data in patients with autoimmune diseases at Southern Medical University Nanfang Hospital from June 7, 2018, to December 31, 2020. The study identified nine important variables for tacrolimus concentration using sequential forward selection, including height, tacrolimus daily dose, other immunosuppressants, low-density lipoprotein cholesterol, mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, direct bilirubin, and hematocrit. The prediction abilities of 14 models based on regression analysis or machine learning algorithms were compared. Ultimately, a prediction model of tacrolimus concentration was established through eXtreme Gradient Boosting (XGBoost) algorithm with the best predictive ability (R 2 = 0.54, mean absolute error = 0.25, and root mean square error = 0.33). Then, SHapley Additive exPlanations was used to visually interpret the variable’s impacts on tacrolimus concentration. In conclusion, the XGBoost model for predicting blood concentration of tacrolimus on the basis of real-world evidence has good predictive performance, providing guidance for the adjustment of regimen in clinical practice.
Help-Seeking Intention in Obsessive-Compulsive Disorder: Predictors and Barriers in South Africa

Introduction: Many individuals with obsessive-compulsive disorder (OCD) delay seeking help, leading to greater illness severity, additional comorbidity, and increased functional impairment. Patterns of help-seeking for OCD have however not yet been described in South Africa, a low-and middle-income country with many health service challenges. Using the health belief model as a conceptual framework, study aims were to identify predictors of and barriers to help-seeking among South Africans with OCD. Methods: Fifty adults with OCD completed an online survey to assess (1) socio-demographic characteristics, (2) OCD symptom severity, (3) treatment barriers, (4) perceived treatment benefits, (5) self-efficacy, and (6) help-seeking intention. Multiple linear regression analysis was used to establish predictors of help-seeking intention. Descriptive statistics were used to determine the most endorsed help-seeking barriers. Results: 42.6% of the variance in help-seeking intention was explained by the investigated constructs (R2 = 0.426, F = 4.45 and p < 0.01). Perceived treatment benefits were the only significant predictor of help-seeking intention (B = 1.37, t = 5.16, and p < 0.01). More than a third (36%) of the sample endorsed wanting to handle the problem independently as a significant barrier, followed by treatment concerns (26%), affordability (22%), and shame (20%). Conclusion: An innovative analysis of help-seeking patterns suggested that perceived treatment benefits were the only significant predictor of help-seeking intention among South African adults with OCD. Psychoeducation and mental health literacy programmes may be useful in increasing public appreciation of the benefits of OCD treatment, and in mitigating key help-seeking barriers.
Inhabiting the Body(ies) in Female Soccer Players: The Protective Role of Positive Body Image

In a social and sports world dominated by weight-centred beliefs and highly exigent and gendered athletic and beauty body standards, the vulnerability for eating pathology, i.e., disordered eating and eating disorders (EDs), is elevated among women athletes. The aim of this study was to explore body image facets and ED risk among female athletes in masculinised sports such as soccer. Forty-five federated amateur female soccer players from Spain participated in this study, voluntarily complying with an extensive evaluation protocol on attitudes towards body and appearance and eating practises. The participants overall reported self-representations of their bodies that corresponded to their reality as athletes, but their body ideals were also more demanding in terms of low fat and muscularity, in association with the functionality of their body and the physical demands of their athletic activity. Despite having a fairly high positive body image and body satisfaction, they also expressed negative attitudes towards their bodies. Around 2 out of 10 players were at risk of suffering from an ED. Players with negative attitudes towards their bodies had an odd 12 times likely to develop an ED compared to those with lower self-devaluation, after adjusting for BMI and body perceptions (OR = 12.3, p < 0.01). On the contrary, players who appreciate their bodies and hold a positive body image had an odd 83% lower to suffer from eating pathology, after adjusting for BMI and body satisfaction (OR = 0.17, p < 0.05). Our findings support the healthy and protective role of positive body image in sports contexts. Body attitudes should be addressed in preventive and therapeutic efforts for reducing the prevalence of EDs in women's sports, within both a “negative” and a “positive” paradigm of body image.
Establishment and Characterization of a Novel Multidrug Resistant Human Ovarian Cancer Cell Line With Heterogenous MRP7 Overexpression

Ovarian cancer is one of the leading female malignancies which accounts for the highest mortality rate among gynecologic cancers. Surgical cytoreduction followed by chemotherapy is the mainstay of treatment. However, patients with recurrent ovarian cancer are likely to exhibit resistance to chemotherapy due to reduced sensitivity to chemotherapeutic drugs. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been extensively studied as multidrug resistance (MDR) mediators since they are responsible for the efflux of various anticancer drugs. Multidrug resistance protein 7 (MRP7, or ABCC10) was discovered in 2001 and revealed to transport chemotherapeutic drugs. Till now, only limited knowledge was obtained regarding its roles in ovarian cancer. In this study, we established an MRP7-overexpressing ovarian cancer cell line SKOV3/MRP7 via transfecting recombinant MRP7 plasmids. The SKOV3/MRP7 cell line was resistant to multiple anticancer drugs including paclitaxel, docetaxel, vincristine and vinorelbine with a maximum of 8-fold resistance. Biological function of MRP7 protein was further determined by efflux-accumulation assays. Additionally, MTT results showed that the drug resistance of the SKOV3/MRP7 cells was reversed by cepharanthine, a known inhibitor of MRP7. Moreover, we also found that the overexpression of MRP7 enhanced the migration and epithelial-mesenchymal transition (EMT) induction. In conclusion, we established an in vitro model of MDR in ovarian cancer and suggested MRP7 overexpression as the leading mechanism of chemoresistance in this cell line. Our results demonstrated the potential relationship between MRP7 and ovarian cancer MDR.
3D Domain Swapping Dimerization of the Receiver Domain of Cytokinin Receptor CRE1 From Arabidopsis thaliana and Medicago truncatula

Cytokinins are phytohormones regulating many biological processes that are vital to plants. CYTOKININ RESPONSE1 (CRE1), the main cytokinin receptor, has a modular architecture composed of a cytokinin-binding CHASE (Cyclases/Histidine kinases Associated Sensory Extracellular) domain, followed by a transmembrane fragment, an intracellular histidine kinase (HK) domain, and a receiver domain (REC). Perception of cytokinin signaling involves (i) a hormone molecule binding to the CHASE domain, (ii) CRE1 autophosphorylation at a conserved His residue in the HK domain, followed by a phosphorelay to (iii) a conserved Asp residue in the REC domain, (iv) a histidine-containing phosphotransfer protein (HPt), and (v) a response regulator (RR). This work focuses on the crystal structures of the REC domain of CRE1 from the model plant Arabidopsis thaliana and from the model legume Medicago truncatula. Both REC domains form tight 3D-domain-swapped dimers. Dimerization of the REC domain agrees with the quaternary assembly of the entire CRE1 but is incompatible with a model of its complex with HPt, suggesting that a considerable conformational change should occur to enable the signal transduction. Indeed, phosphorylation of the REC domain can change the HPt-binding properties of CRE1, as shown by functional studies.