Miracle-dz/UniFAR-FTUs huggingface dataset:
Ovarian cancer: screening and future directions

Ovarian cancer carries a lifetime risk of approximately 2% for women and is the leading cause of death from any gynecologic malignancy. Currently, no screening program for ovarian cancer exists for the general population in the UK. This review focuses on the evidence surrounding the efficacy of current markers and discusses future improvements in screening for this disease. One-off cancer antigen 125 (CA125) measurements for detecting ovarian cancer have been well researched. However, studies have highlighted low positive predictive values (5%) and high false positive rates leading to patient anxiety and unnecessary invasive follow-up. Commonly, in the UK, CA125 is combined with transvaginal ultrasound, but there is little evidence that this approach can decrease mortality from ovarian cancer. Recently the Risk of Ovarian Cancer Algorithm, involving a combination of serial CA125 measurements and age, has been shown to detect more early stage cancers. Nevertheless, these measures are not robust in decreasing mortality from ovarian cancer and are costly to implement. Newer markers, such as human epididymis protein 4, have shown greater specificity. Its combination with CA125 and menopausal status in the Risk of Ovarian Malignancy Algorithm can predict the risk of malignancy but provides no additional benefit as a screening tool. Advanced techniques are emerging, including ultrasound molecular imaging techniques using microbubbles targeted to kinase domain receptors, and fallopian tube cytology. To reduce mortality from ovarian cancer, detection of pre-invasive lesions is imperative as ovarian cancer may develop in the fallopian tube and spread to the peritoneal cavity before being detected systemically. It seems that screening tools for ovarian cancer are currently not worthwhile for implementation into a national program. An emphasis on reducing false positives rates, associated anxiety and subsequent overdiagnosis is needed.
Profiles and academic trajectories of cognitively gifted children with autism spectrum disorder

Gifted children with autism spectrum disorder (ASD) are often referred to as twice-exceptional, the term that highlights the co-occurrence of exceptional challenges and exceptional giftedness. This study performed secondary data analysis on samples of twice-exceptional children from the Pre-Elementary Education Longitudinal Study and the Special Education Elementary Longitudinal Study datasets. The results provide a descriptive profile of twice-exceptional (e.g. demographics, average academic performance, and services utilized), trajectory plots that indicate how academic performance changes over time, and multilevel analyses that model growth in academic outcomes using demographics, school services, and giftedness as predictors. Some of the key findings are that twice-exceptional students show not only higher initial levels of academic performance, but they improve over time relative to the non-gifted ASD counterparts and—with the exception of Letter Word Matching—even relative to the general population. Moreover, they benefit from mental health services disproportionately. Together, the results offer a deeper understanding of the twice-exceptional autistic population, their academic performance over time, and the services that they utilize.
Are low‐carbohydrate diets safe in diabetic and nondiabetic chronic kidney disease?

Diabetes mellitus and obesity both contribute to chronic kidney disease (CKD) and diabetic kidney disease (DKD), and they can accelerate the loss of kidney function. Dietary intake can potentially have wide‐reaching effects on the risk of CKD/DKD and their progression by reducing weight and blood pressure, improving glycemic control, reducing hyperfiltration, and modulating inflammation. Low‐carbohydrate (LC) diets can reduce weight and improve glycemic control, but the relatively higher protein content also raises concern in CKD/DKD. Empiric evidence supporting the kidney‐related benefits or risks of LC diets is needed to understand the balance of these potential harms and benefits for patients with DKD and is the subject of our review.
Magnetic resonance imaging (MRI) compared with computed tomography (CT) for interobserver agreement of gross tumor volume delineation in pancreatic cancer: a multi-institutional contouring study on behalf of the AIRO group for gastrointestinal cancers

Abstract Background: Due to the high soft tissue resolution, magnetic resonance imaging (MRI) could improve the accuracy of pancreatic tumor delineation in radiation treatment planning. A multi-institutional study was proposed to evaluate the impact of MRI on inter-observer agreement in gross tumor volume (GTV) and duodenum delineation for pancreatic cancer compared with computer tomography (CT). Material and Methods: Two clinical cases of borderline resectable (Case 1) and unresectable (Case 2) pancreatic cancer were selected. In two sequential steps, diagnostic contrast-enhanced CT scan and MRI sequences were sent to the participating centers. CT-GTVs were contoured while blinded to MRI data sets. DICE index was used to evaluate the spatial overlap accuracy. Results: Thirty-one radiation oncologists from different Institutions submitted the delineated volumes. CT- and MRI-GTV mean volumes were 21.6 ± 9.0 cm3 and 17.2 ± 6.0 cm3, respectively for Case 1, and 31.3 ± 15.6 cm3 and 33.2 ± 20.2 cm3, respectively for Case 2. Resulting MRI-GTV mean volume was significantly smaller than CT–GTV in the borderline resectable case (p < .05). A substantial agreement was shown by the median DICE index for CT– and MRI–GTV resulting as 0.74 (IQR: 0.67–0.75) and 0.61 (IQR: 0.57–0.67) for Case 1; a moderate agreement was instead reported for Case 2: 0.59 (IQR:0.52–0.66) and 0.53 (IQR:0.42–0.62) for CT– and MRI–GTV, respectively. Conclusion: Diagnostic MRI resulted in smaller GTV in borderline resectable case with a substantial agreement between observers, and was comparable to CT scan in interobserver variability, in both cases. The greater variability in the unresectable case underlines the critical issues related to the outlining when vascular structures are more involved. The integration of MRI with contrast-enhancement CT, thanks to its high definition of tumor relationship with neighboring vessels, could offer a greater accuracy of target delineation.
Accuracy of Frozen-Section Diagnosis of Brain Tumors: An 11-Year Experience from a Tertiary Care Center.

AIM To analyze the frozen section (FS) diagnostic accuracy in correlation with the final diagnosis of brain tumors. MATERIAL AND METHODS This retrospective study comprised all brain tumor cases with FS diagnosis and permanent section diagnosis in Jordan University Hospital from July 1, 2007 to December 31, 2017. Data were obtained by reviewing slides and reports from the histopathology archives. Statistical Package for the Social Science (SPSS) software v20 was used for analysis. RESULTS A total of 179 cases with frozen section and permanent section diagnoses were analyzed. Eighty-four (47%) patients were males and 95 (53%) females.The ages ranged from 1 to 85 years. Diagnostic accuracy of FS was 88.8%. Discrepancy was noted in 20 cases. Of the discrepancies, misclassification of tumor type was the most common category (12 cases, 60%), followed by grading mismatch (7 cases, 35%) and misdiagnosis of tumor versus non-tumor conditions (1 case, 5%). Patient age and gender were not significantly associated with the discrepancy between FS and final diagnosis. CONCLUSION Our results were comparable to international reports. However, more emphasis on diagnostic cytology in intraoperative consultation is required as an effective adjunct to frozen section to overcome limitations.
A Systematic Review of Closed Head Injury Models of Mild Traumatic Brain Injury in Mice and Rats

Abstract Mild TBI (mTBI) is a significant health concern. Animal models of mTBI are essential for understanding mechanisms, and pathological outcomes, as well as to test therapeutic interventions. A variety of closed head models of mTBI that incorporate different aspects (i.e., biomechanics) of the mTBI have been reported. The aim of the current review was to compile a comprehensive list of the closed head mTBI rodent models, along with the common data elements, and outcomes, with the goal to summarize the current state of the field. Publications were identified from a search of PubMed and Web of Science and screened for eligibility following PRISMA guidelines. Articles were included that were closed head injuries in which the authors classified the injury as mild in rats or mice. Injury model and animal-specific common data elements, as well as behavioral and histological outcomes, were collected and compiled from a total of 402 articles. Our results outline the wide variety of methods used to model mTBI. We also discovered that female rodents and both young and aged animals are under-represented in experimental mTBI studies. Our findings will aid in providing context comparing the injury models and provide a starting point for the selection of the most appropriate model of mTBI to address a specific hypothesis. We believe this review will be a useful starting place for determining what has been done and what knowledge is missing in the field to reduce the burden of mTBI.
Direct Hospitalization Cost of Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Vietnam

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have been found to contribute, predominantly, to increasing costs of COPD—a major public health issue. This study aimed to fill the gap in literature concerning costs of AECOPD in Vietnam, by examining the direct cost of AECOPD hospitalization and determining potentially associated factors. A cross-sectional study was conducted at the Respiratory Center of Bach Mai Hospital, Hanoi. A total of 57 participants were selected. Information regarding sociodemographic features, clinical characteristics, and hospitalization costs were collected. A multivariate generalized linear regression model was utilized to determine the factors associated with hospitalization costs. The mean total and daily hospitalization cost were 18.3 million VND (SD = 12.9) and 2.5 million VND (SD = 3.2), respectively. Medication cost accounted for 53.9% of hospitalization cost (from 44.0% in the Global Initiative for Chronic Obstructive Lung Disease Classification A (GOLD A) to 55.3% in GOLD C). Patients having GOLD D COPD (Coef. = 5.78; 95% CI = 0.73–10.83), higher age (Coef. = 0.37; 95% CI = 0.13–0.61), and higher duration of hospitalization (Coef. = 1.91; 95% CI = 1.28–2.53) had higher hospitalization costs (p < 0.05). This study suggested that interventions to screen COPD patients as well as provide timely treatment should be conducted widely in the community in order to avoid any unnecessary hospitalization cost, consequently reducing the economic burden of COPD.
Differential YAP expression in glioma cells induces cell competition and promotes tumorigenesis

ABSTRACT Intratumor heterogeneity associates with cancer progression and may account for a substantial portion of therapeutic resistance. Although extensive studies have focused on the origin of the heterogeneity, biological interactions between heterogeneous malignant cells within a tumor are largely unexplored. Glioblastoma (GBM) is the most aggressive primary brain tumor. Here, we found that the expression of Yes-associated protein (YAP, also known as YAP1) is intratumorally heterogeneous in GBM. In a xenograft mouse model, differential YAP expression in glioma cells promotes tumorigenesis and leads to clonal dominance by cells expressing more YAP. Such clonal dominance also occurs in vitro when cells reach confluence in the two-dimensional culture condition or grow into tumor spheroids. During this process, growth of the dominant cell population is enhanced. In the tumor spheroid, such enhanced growth is accompanied by increased apoptosis in cells expressing less YAP. The cellular interaction during clonal dominance appears to be reminiscent of cell competition. RNA-seq analysis suggests that this interaction induces expression of tumorigenic genes, which may contribute to the enhanced tumor growth. These results suggest that tumorigenesis benefits from competitive interactions between heterogeneous tumor cells. Summary: This study reveals a functional consequence of intratumor heterogeneity in YAP expression, and suggests that tumorigenesis benefits from competitive interactions between heterogeneous tumor cells.
Impact of the Nutrition-Friendly School Initiative: analysis of anthropometric and biochemical data among school-aged children in Ouagadougou

The Nutrition-Friendly School Initiative was developed in 2006 to counter the double burden of malnutrition and implemented on a pilot basis in primary schools in Ouagadougou (Burkina Faso) in 2009. A baseline study was conducted in intervention and control schools and repeated in 2014 to assess the impact. This paper reports on anthropometric and biochemical data in the final and baseline surveys. Both studies were conducted in the fifth grade classes of the same primary schools in Ouagadougou. Six intervention schools had been selected and matched at baseline with six control schools. The total sample consisted of 699 and 651 pupils in 2009 and 2014, respectively. Anthropometric and hemoglobin measurements were performed on all children, whereas serum retinol was measured in a random subsample to assess Vitamin A Deficiency (VAD). Independent t-tests and chi-squared tests were used for comparison of means and proportions, respectively, and multiple logistic regressions were conducted to examine associations between nutritional parameters and school characteristics. Final rates of anaemia and VAD were 32.6% and 26.1%, respectively, down from 40.4% and 38.7% at baseline. The final prevalence rate of stunting was 8.1%, thinness was 8.7% and overweight/obesity was 4.4%. Thinness declined significantly in 2014 compared to 2009, but there was no change in the rate of stunting even though the rate of overweight/obesity showed an upward trend. When comparing intervention with control schoolchildren, the only significant differences found in the final survey were less thinness and less anaemia in the intervention children. However, the prevalence of anaemia was also significantly lower in the intervention group at baseline. Our results point to a significant improvement in the nutritional status of schoolchildren in Ouagadougou and suggest a positive, although modest, role for the Nutrition-Friendly School Initiative in reducing thinness, but not overweight.
Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK

Increasing evidence indicates that environmental tobacco smoke (ETS) impairs cognitive function and induces oxidative stress in the brain. Recently, astaxanthin (ATX), a marine bioactive compound, has been reported to ameliorate cognitive deficits. However, the underlying pathogenesis remains unclear. In this study, ATX administration (40 mg/kg and 80 mg/kg, oral gavage) and cigarette smoking were carried out once a day for 10 weeks to investigate whether the p38 MAPK is involved in cognitive function in response to ATX treatment in the cortex and hippocampus of ETS mice. Results indicated that ATX administration improved spatial learning and memory of ETS mice (p < 0.05 or p < 0.01). Furthermore, exposure to ATX prevented the increases in the protein levels of the p38mitogen-activated protein kinase (p38 MAPK; p < 0.05 or p < 0.01) and nuclear factor-kappa B (NF-κB p65; p < 0.05 or p < 0.01), reversed the decreases in the mRNA and protein levels of synapsin I (SYN) and postsynaptic density protein 95 (PSD-95) (all p < 0.05 or p < 0.01). Moreover, ATX significantly down-regulated the increased levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) (all p < 0.05 or p < 0.01). Meanwhile, the increased level of malondialdehyde (MDA) and the decreased activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were suppressed after exposure to ATX (all p < 0.05 or p < 0.01). Also, the results of the molecular docking study of ATX into the p38 MAPK binding site revealed that its mechanism was possibly similar to that of PH797804, a p38 MAPK inhibitor. Therefore, our results indicated that the ATX might be a critical agent in protecting the brain against neuroinflammation, synaptic plasticity impairment, and oxidative stress in the cortex and hippocampus of ETS mice.
Denosumab effects on serum levels of the bone morphogenetic proteins antagonist noggin in patients with transfusion-dependent thalassemia and osteoporosis

ABSTRACT Introduction: Noggin is an antagonist of bone morphogenetic proteins (BMPs) and has a strong effect on osteogenesis. Osteoporosis is a common complication of transfusion dependent beta-thalassemia (TDT) and denosumab has been recently emerged as a promising therapeutic option. This was a post hoc investigation of serum noggin levels among TDT patients with osteoporosis who participated in a randomized, placebo-control, phase 2b study. Methods: Patients received either 60 mg denosumab (n = 32) or placebo (n = 31) every 6 months for 12 months. Noggin was measured, for the first time in thalassemia patients, at baseline and at 12 months, using a recently developed high sensitivity fluorescent immunoassay. Results: Both groups showed a significant increase in noggin serum levels (denosumab p < 0.001; placebo p < 0.0001). Interestingly, the increase was higher in the placebo group. Furthermore, we observed a strong correlation between noggin and wrist bone mineral density (r = −0.641, p = 0.002) only in the denosumab group. Conclusion: In conclusion, higher noggin levels reflected more BMP inhibition, since our assay detects free bioactive noggin, which in turn impaired bone formation in placebo group. Therefore, denosumab possibly regulates noggin and favours bone turnover in TDT patients with osteoporosis through a novel mechanism of action. Trial registration: ClinicalTrials.gov identifier: NCT02559648.
Sex‐related differences of clinical features in hidradenitis suppurativa: analysis of an Italian‐based cohort

The clinical characteristics associated with hidradenitis suppurativa (HS) severity are poorly understood. In this study, 124 patients with HS from 6 Italian dermatology centres participated in this study. Disease severity was assessed using the Hidradenitis Suppurativa Physician's Global Assessment score (HS‐PGA) and Hurley score. The impact of clinical characteristics on disease severity was assessed by logistic regression. Clinical characteristics were similar between men (n = 53) and women (n = 71). Disease severity was also similar; 75% of the patients had Hurley stage II or III disease, and > 60% had moderate, severe or very severe HS as judged by HS‐PGA. Lesions were more frequent in the gluteal region in men (32.3% in men vs. 8.7% in women, P < 0.001) and more frequent on the breast in women (16.3% in women vs. 4.6% in men, P = 0.02). Obesity was associated with increased disease severity as measured by HS‐PGA (OR: 3.28, 95% CI 1.55–6.95, P < 0.01) and Hurley classification (OR: 3.22, 95% CI 1.34–7.31, P < 0.01). Although severity of HS is similar between the sexes, the localization of lesions is different.
Clinical, Radiologic, and Prognostic Features of Myelitis Associated With Myelin Oligodendrocyte Glycoprotein Autoantibody

Importance Recognizing the characteristics of myelin oligodendrocyte glycoprotein autoantibody (MOG-IgG) myelitis is essential for early accurate diagnosis and treatment. Objective To evaluate the clinical, radiologic, and prognostic features of MOG-IgG myelitis and compare with myelitis with aquaporin-4–IgG (AQP4-IgG) and multiple sclerosis (MS). Design, Setting, and Participants We retrospectively identified 199 MOG-IgG–positive Mayo Clinic patients from January 1, 2000, through December 31, 2017, through our neuroimmunology laboratory. Fifty-four patients met inclusion criteria of (1) clinical myelitis; (2) MOG-IgG positivity; and (3) medical records available. We excluded 145 patients without documented myelitis. Myelitis of AQP4-IgG (n = 46) and MS (n = 26) were used for comparison. Main Outcomes and Measures Outcome variables included modified Rankin score and need for gait aid. A neuroradiologist analyzed spine magnetic resonance imaging of patients with MOG-IgG and control patients blinded to diagnosis. Results Of 54 included patients with MOG-IgG myelitis, the median age was 25 years (range, 3-73 years) and 24 were women (44%). Isolated transverse myelitis was the initial manifestation in 29 patients (54%), and 10 (19%) were initially diagnosed as having viral/postviral acute flaccid myelitis. Cerebrospinal fluid–elevated oligoclonal bands occurred in 1 of 38 (3%). At final follow-up (median, 24 months; range, 2-120 months), 32 patients (59%) had developed 1 or more relapses of optic neuritis (n = 31); transverse myelitis (n = 7); or acute disseminated encephalomyelitis (n = 1). Clinical features favoring MOG-IgG myelitis vs AQP4-IgG or MS myelitis included prodromal symptoms and concurrent acute disseminated encephalomyelitis. Magnetic resonance imaging features favoring MOG-IgG over AQP4-IgG or MS myelitis were T2-signal abnormality confined to gray matter (sagittal line and axial H sign) and lack of enhancement. Longitudinally extensive T2 lesions were of similar frequency in MOG-IgG and AQP4-IgG myelitis (37 of 47 [79%] vs 28 of 34 [82%]; P = .52) but not found in MS. Multiple spinal cord lesions and conus involvement were more frequent with MOG-IgG than AQP4-IgG but not different from MS. Wheelchair dependence at myelitis nadir occurred in one-third of patients with MOG-IgG and AQP4-IgG but never with MS, although patients with MOG-IgG myelitis recovered better than those with AQP4-IgG. Conclusions and Relevance Myelitis is an early manifestation of MOG-IgG–related disease and may have a clinical phenotype of acute flaccid myelitis. We identified a variety of clinical and magnetic resonance imaging features that may help clinicians identify those at risk in whom MOG-IgG should be tested.
A self‐excited threshold autoregressive state‐space model for menstrual cycles: Forecasting menstruation and identifying within‐cycle stages based on basal body temperature

The menstrual cycle is divided into hypothermic and hyperthermic phases based on the periodic shift in the basal body temperature (BBT), reflecting events occurring in the ovary. In the present study, we proposed a state‐space model that explicitly incorporates the biphasic nature of the menstrual cycle, in which the probability density distributions for the advancement of the menstrual phase and that for the BBT switch depending on a latent state variable. Our model derives the predictive distribution of the day of the next menstruation onset that is adaptively adjusted by accommodating new observations of the BBT sequentially. It also enables us to obtain conditional probabilities of the woman being in the early or late stages of the cycle, which can be used to identify the duration of hypothermic and hyperthermic phases, possibly as well as the day of ovulation. By applying the model to real BBT and menstruation data, we show that the proposed model can properly capture the biphasic characteristics of menstrual cycles, providing a good prediction of the menstruation onset in a wide range of age groups. The application of the proposed model to a large data set containing 25 622 cycles provided by 3533 women further highlighted the between‐age differences in the population characteristics of menstrual cycles, suggesting its wide applicability.