Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Stimulated Cycles with Low Dose r-FSH versus Hormone Replacement Cycles for Endometrial Preparation Prior to Frozen-Thawed Embryo Transfer in Young Women with Polycystic Ovarian Syndrome: A Single-Center Retrospective Cohort Study from China

Objective The principal purpose of this study was to compare reproductive outcomes for stimulated cycles (STC) and hormone replacement cycles (HRC) for endometrial preparation before frozen-thawed embryo transfer (FET) in young women with polycystic ovary syndrome (PCOS). Methods We conducted a retrospective study of 1434 FET cycles from January, 2017 to March, 2020 in our reproductive center, in which stimulated and hormone replacement cycles were used for endometrial preparation. Pregnancy outcomes of couples undergoing routine STC-FET or HRC-FET were analyzed by propensity score matching (PSM) and multivariable logistic regression analyses. Results Data on 1234 HRC protocols (86% of the total) and 200 STC protocols (14%) were collected. After PSM, 199 patients were included in both groups, respectively. There was no significant difference in positive pregnancy rate (52.7% vs 54.8%, p=0.763), clinical pregnancy rate (51.8% vs 52.8%, p=0.841), live birth rate (45.2% vs 43.7%, p=0.762), pregnancy loss rate (9.7% vs 16.2%, p=0.164) and ectopic pregnancy rate (1.5% vs 0.5%, p=0.615) between STC and HRC protocols. Subsequent multivariate logistic regression analysis also yielded similar results. Conclusion STC for endometrial preparation had similar pregnancy outcomes compared with HRC protocols. Evidence is available which shows that for young women with PCOS in preparation for FET, HRC could be a reasonable choice for patients who are unwilling to accept injections. However, STC may reduce unnecessary anxiety and operational costs and offer more flexibility for patients. Eventually, we must embrace the concepts of individualization, securitization, and optimization in the clinic.
Healthy Hearts for an Abundant Life: Feasibility of a Culturally Adapted Cardiovascular Disease Prevention Curriculum for African American Women

Background: This study tested the feasibility of implementing Healthy Hearts for an Abundant Life (HHAL), a cultural adaptation for African American (AA) women of the evidence-based cardiovascular disease prevention program Strong Women-Healthy Hearts (SWHH). Methods: Using a quasi-experimental pre-post study design, this 12-week program was implemented in four faith-based organizations between 2017 and 2018. Eligible participants were AA women between 40 and 65 years who had a body mass index of 25 or higher and were currently sedentary. HHAL program participants met weekly for 2-h sessions led by program leaders. The curriculum has four modules: total health; relationships, family, and networks; material security and the environment; and emotional wellness. Each class included walking for 30 min, goal-setting session, and a group dialog called “making it work” for building collective efficacy. Results: Of the 27 participants (mean age=54.2±5.9), 24 completed postassessments (93% retention rate). All outcome measures proved feasible and weekly program attendance was 73%. Findings from in-depth interviews show high satisfaction with the program and suggest extending the class time and adding cooking demonstrations. Conclusions: The culturally adapted HHAL proved feasible and was positively received by the participants. Future studies will evaluate the effectiveness of the program.
Prevalence and Determinants of Pre-Cancerous Cervical Lesion and Human Papillomavirus Among HIV-Infected and HIV-Uninfected Women in North-West Ethiopia: A Comparative Retrospective Cross-Sectional Study

Background The poor socio-economic status, underdeveloped health care system, and the high HIV/AIDS burden have potentially increased the incidence of cervical cancer in sub-Saharan Africa (SSA) including Ethiopia. Studies on the magnitude of pre-cancerous cervical lesion and human papillomavirus (HPV) among HIV-infected women are still limited, particularly in the current study setting. Thus, we determined the prevalence of pre-cancerous cervical lesion and HPV among HIV-infected women in comparison with HIV-uninfected women at Debre Tabor Comprehensive Specialized Hospital (DTCSH), North-West Ethiopia. Methods Hospital-based comparative retrospective cross-sectional study was conducted among 546 women from July 2018 to January 2020 at DTCSH. All records during the study period were collected using a structured checklist. Epi data version 4.02 and SPSS version 25.0 were used for data entry and analysis, respectively. Results The overall prevalence of pre-cancerous cervical lesion among 546 women was 8.8%. The prevalence of pre-cancerous cervical lesion was comparable between HIV-infected (9.3%) and HIV-uninfected women (8.6%) (p = 0.859). Age >45 years old, widowed marital status, multiparous (women ≥ 5 childbirths), and educational status were independent contributing factors of a pre-cancerous cervical lesion. Regarding HPV prevalence, among 109 screened women, 7 (6.4%) were positive for both HPV 16 and 18 strains. Conclusion HIV infection was not statistically correlated with the magnitude of pre-cancerous cervical lesion (p = 0.859). Women in the study setting developed pre-cancerous cervical lesions irrespective of their HIV status. Hence, we recommend routine screening of women for pre-cancerous cervical lesion and HPV infection regardless of their HIV status for early management and prevention of associated morbidity and/or mortality.
Effective Strategies to Predict Survival of Colorectal Peritoneal Metastases Patients Eligible for Cytoreductive Surgery and HIPEC

Abstract Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), often combined with systemic therapy, can be offered to selected colorectal peritoneal metastases (PM) patients. However, clinical heterogeneity and the lack of high-level evidence challenges determination of the correct treatment strategy. This review aims to provide an overview of current strategies to predict survival of colorectal PM patients treated with CRS and HIPEC, guiding clinicians to select a suitable treatment-strategy and to inform patients about their prognosis. First, the prognostic relevance of several clinicopathological prognostic factors, such as extent of PM, location of primary tumor, histology type, and the presence of lymph node or liver metastases will be discussed. Subsequently, special attention will be given to recent developments in several aspects of tumor biology such as RAF/RAS mutations, circulating tumor DNA, immunoprofiling, and consensus molecular subtypes. Finally, currently available prognostic models to predict survival will be evaluated, concluding these models perform moderate to good, but most of them partly rely on intra-operative data. New insights in tumor biology, as well as the reliable assessment of extent of peritoneal disease by diffusion weighted MRI pose promising opportunities to establish an adequate and clinically meaningful preoperative prognostic model in the near future.
A Calibrated Multiexit Neural Network for Detecting Urothelial Cancer Cells

Deep convolutional networks have become a powerful tool for medical imaging diagnostic. In pathology, most efforts have been focused in the subfield of histology, while cytopathology (which studies diagnostic tools at the cellular level) remains underexplored. In this paper, we propose a novel deep learning model for cancer detection from urinary cytopathology screening images. We leverage recent ideas from the field of multioutput neural networks to provide a model that can efficiently train even on small-scale datasets, such as those typically found in real-world scenarios. Additionally, we argue that calibration (i.e., providing confidence levels that are aligned with the ground truth probability of an event) has been a major shortcoming of prior works, and we experiment a number of techniques to provide a well-calibrated model. We evaluate the proposed algorithm on a novel dataset, and we show that the combination of focal loss, multiple outputs, and temperature scaling provides a model that is significantly more accurate and calibrated than a baseline deep convolutional network.
Insulin sensitization causes accelerated sinus nodal dysfunction through autophagic dysregulation in hypertensive mice

Insulin sensitizers, while effective in glucose-lowering for diabetes control, are linked to an increased risk of heart disease through mechanisms that are not well understood. In this study, we investigated the molecular mechanisms underlying the effects of insulin sensitization on cardiac sinus node dysfunction. We used pharmacologic or genetic approaches to enhance insulin sensitivity, by treating with pioglitazone or rosiglitazone, or through phosphatase and tensin homolog (PTEN) deletion in cardiomyocytes respectively. We employed an angiotensin II (Ang II)-induced hypertensive animal model which causes sinus node dysfunction and accumulation of oxidized calcium/calmodulin-dependent protein kinase II (CaMKII), which also serves as a biomarker for this defect. While neither PTEN deficiency nor insulin sensitizers caused sinus node dysfunction in normotensive mice, both accelerated the onset of sinus node dysfunction and CaMKII oxidation in hypertensive mice. These abnormalities were accompanied by a significant defect in autophagy as revealed by unc-51 like autophagy activating kinase 1 (ULK1) signaling. Indeed, mice deficient in ulk1 in cardiomyocytes and the sinus node also showed early onset of slow atrial impulse conduction with frequent sinus pauses and upregulated CaMKII oxidation following Ang II infusion similar to that seen with PTEN deficiency, or treatment with insulin sensitizers. To further elucidate the role of autophagy in sinus node dysfunction, we treated mice with a peptide D-Tat-beclin1 that enhanced autophagy, which significantly abrogated the frequent sinus pauses and accumulation of oxidized CaMKII induced by insulin sensitizers treatment, or PTEN deficiency in hypertensive animals. Together, these findings provide clear evidence of the detrimental cardiac effects of insulin sensitization that occurs through failure of autophagy-mediated proteolytic clearance.
Using strain gradient elasticity in conjunction with Gurtin–Murdoch theory for modeling the coupled effects of surface and size phenomena on the instability of narrow nano-switch

While comprehensive researches have been conducted on modeling the electromechanical stability of wide-enough beam-plate nano-switches, few researchers have focused on modeling the electromechanical instability of narrow-width nano-switches. For such systems, considering the coupled effects of surface stresses and size dependency of material characteristics is crucial as well as applying appropriate force models. In this paper, Gurtin–Murdoch surface theory incorporating with strain gradient elasticity is employed to study the pull-in instability of narrow-width beam-type nano-switch with small width to height ratio. The model accounts for the force corrections, i.e. the impact of finite dimensions on the fringing field, Casimir attraction and van der Waals force. Furthermore, a modified gas damping model has been incorporated in the governing equation. The nonlinear governing equation was solved using analytical Rayleigh–Ritz method. The influences of the above-mentioned corrections on the static and dynamic pull-in parameters, phase planes and stability threshold of the switch are demonstrated. The modified model is compared with conventional parallel beam-plate models in the literature.
LncRNA AFAP1-AS1 Modulates the Proliferation and Invasion of Gastric Cancer Cells by Regulating AFAP1 via miR-205-5p

Purpose The present study investigated the expression and function of the long noncoding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) related to gastric cancer (GC), based on previous results from a microarray analysis. Methods Real-time quantitative polymerase chain reaction (qPCR) was used to verify the expression of AFAP1-AS1 in 97 fresh GC tissues and paired non-GC tissues, as well as in six different GC cell lines (BGC-823, SGC-7901, MGC-803, AGS, MKN-45, and MKN-28). The expression levels were subsequently correlated with the clinicopathological features of patients. siRNA against AFAP1-AS1 was transfected into GC cell lines, and cell proliferation, migration, and invasion were detected before and after silencing of AFAP1-AS1 expression. Luciferase reporter gene analysis was used to confirm the target gene of microRNA-205-5p (miR-205-5p) in 293T cells. The potential mechanism was subsequently investigated. Results qPCR results showed that AFAP1-AS1 was significantly overexpressed in GC tumor tissues and also GC cell lines, comparing to their paired non-GC tissues. Furthermore, statistical analysis revealed that the overexpression of AFAP1-AS1 was significantly correlated with tumor size (p=0.018) and grade of differentiation (p=0.042). Subsequently, artificially decreasing the expression of AFAP1-AS1 with its specific siRNA dramatically inhibited the proliferation, migration and invasion of GC cell lines (SGC-7901 and BGC-823 cells). Mechanical analysis suggested that AFAP1-AS1 is involved in regulation of its maternal gene, AFAP1, at both mRNA level and protein level. Luciferase reporter gene assay indicated that lncRNA AFAP1-AS1, as a ceRNA, is able to sponge miR-205-5p. Moreover, miR-205-5p has been well demonstrated to participate in the regulation of AFAP1 expression and the phenotypes of GC cells, including proliferation, migration and invasion. Conclusion AFAP1-AS1, as a novel biomarker of GC, promotes the proliferation migration and invasion of GC cells and function as ceRNA to target AFAP1 by sponging miR-205-5p.
Development and External Validation of Safe Discharge Criteria After Radical Gastrectomy

Aim Enhanced recovery after surgery (ERAS) gradually shortens the length of stay but increases the rate of unplanned readmission after discharge. Currently, objective discharge criteria for patients after radical gastrectomy is lacking. This study aimed to construct and validate a nomogram for estimation of the possibility of safe discharge on the fifth-day post radical gastrectomy. Methods We enrolled 496 consecutive patients undergoing radical gastrectomy as the development cohort. After the fifth day of surgery, patients were assigned to the postoperative complication group and no postoperative complication group. Multivariate logistic regression analyses were performed for both groups. Then, we constructed the risk prediction model of postoperative severe complications (PSCs) and applied it to evaluate whether the patient could be discharged safely. The external validation cohort comprised 245 patients, whom we used to evaluate the capability of our model to predict the risk of PSCs. The primary measure was the negative predictive rate (NPR) and the area under the curve (AUC). Results Through multivariate analysis, gender, maximum body temperature on the 4th postoperative day (POD4), oral intake and ambulatory duration on POD4, the proportion of neutrophils (≥75% or <75%) and pain score (≥4 or <4) on POD5, and defecation with 5 days after the procedure (yes or no) were identified as independent predictors for PSCs. Upon incorporation of these variables, the nomogram demonstrated a good NPR of 0.957 and 0.916 and AUC of 0.918 and 0.719 in the two cohorts, respectively. With a nomogram score of 110, patients were stratified into low and high risk of PSCs. Conclusion The nomogram demonstrated good predictive potential for low-risk patients. It could serve as an objective safe discharge approach for patients after the fifth day of radical gastrectomy.
Targeting KRAS mutations with HLA class II-restricted TCRs for the treatment of solid tumors

ABSTRACT T-cell receptor (TCR) redirected T cells are considered as the next generation of care for the treatment of numerous solid tumors. KRAS mutations are driver neoantigens that are expressed in over 25% of all cancers and are thus regarded as ideal targets for Adoptive Cell Therapy (ACT). We have isolated four KRAS-specific TCRs from a long-term surviving pancreatic cancer patient vaccinated with a mix of mutated KRAS peptides. The sequence of these TCRs could be identified and expressed in primary cells. We demonstrated stable expression of all TCRs as well as target-specific functionality when expressing T cells were co-incubated with target cells presenting KRAS peptides. In addition, these TCRs were all partially co-receptor independent since they were functional in both CD4 and CD8 T cells, thus indicating high affinity. Interestingly, we observed that certain TCRs were able to recognize several KRAS mutations in complex with their cognate Human leukocyte antigen (HLA), suggesting that, here, the point mutations were less important for the HLA binding and TCR recognition, whereas others were single-mutation restricted. Finally, we demonstrated that these peptides were indeed processed and presented, since HLA-matched antigen presenting cells exogenously loaded with KRAS proteins were recognized by TCR-transduced T cells. Taken together, our data demonstrate that KRAS mutations are immunogenic for CD4 T cells and are interesting targets for TCR-based cancer immunotherapy.
Asymmetry of Edema Formation: The Possibility of a Somatic Mosaic

A 57-year-old woman experienced an abnormal feeling on the left side of her neck and difficulty breathing 90 minutes after eating Chinese noodles. She had a history of removal of a left sphenoid ridge meningioma one year earlier. She had experienced rigidity of her left neck and peripheral cold sensation on her left side in winter since approximately 10 years of age. She had experienced peripheral swelling of her left side and lower back pain of unknown origin on her left side several times. She had suffered for oral allergy syndrome since she was young. She sometimes experienced a tingling sensation on her lips and an unpleasant feeling in her throat after eating some types of fruit. On arrival, 180 minutes after eating the noodles, she had clear consciousness and stable vital signs. She had left neck and chest swelling without color change. Her difficulty breathing subsided spontaneously. A blood analysis revealed an increased level of immunoglobulin E. Neck computed tomography (CT) with contrast medium and magnetic resonance imaging (MRI) revealed left-side-limited edema in the subcutaneous area and surrounding esophagus and bronchus. These radiological findings denied hemorrhaging or pseudoaneurysmal formation. She underwent observational admission. After her edema improved, she was discharged on the third hospital day. A follow-up examination one week later showed the complete resolution of the neck and chest edema. A blood allergen test did not reveal the cause of the edema. The mechanism underlying the asymmetric transient edema after eating in the present case may involve somatic mosaic.
Outcomes of “Real-World” Insulin Strategies in the Management of Hospital Hyperglycemia

Abstract Context Guidelines recommend scheduled long-acting basal and short-acting bolus insulin several times daily to manage inpatient hyperglycemia. In the “real world,” insulin therapy is complicated, with limited data on the comparative effectiveness of different insulin strategies. Objective This work aimed to evaluate the association of different insulin strategies with glucose control and hospital outcomes after adjustment for patient and physician factors that influence choice of therapy. Methods This retrospective, observational study took place at an academic hospital. Participants included noncritically ill hospitalized medical/surgical patients (n = 4558) receiving subcutaneous insulin for 75% or longer during admission. Insulin therapy was grouped into 3 strategies within the first 48 hours: basal bolus (BB: scheduled long and short/rapid n = 2358), sliding scale (SS: short/rapid acting n = 1855), or basal only (BO: long only: n = 345). Main outcome measures included glucose control: hypoglycemic days, hyperglycemic days, euglycemic days, mean glucose; and hospitalization: in-hospital mortality, length of stay (LOS), and readmissions. Results Initial therapy with BB was associated with more hypoglycemic (2.40; CI, 2.04 to 2.82) (P < .001) and fewer euglycemic days (0.90; CI, 0.85 to 0.97) (P = .003) than SS, whereas BO was associated with fewer hyperglycemic days (0.70; CI, 0.62 to 0.79) (P < .001), lower mean glucose (–18.03; CI, –22.46 to –12.61) (P < .001), and more euglycemic days (1.22; CI, 1.09 to 1.37) (P < .001) compared to SS. No difference in mortality, LOS, and readmissions was found. However, decreased LOS was observed in the BB subgroup with a medical diagnostic related group (0.93; CI, 0.89 to 0.97) (P < .001). Conclusion BO had a more favorable hyperglycemia profile than SS. BB, on the other hand, showed worse glycemic control as compared to SS. In the real-world hospital, BO may be a simpler and more effective insulin strategy.
Safety Profile of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease

Abstract Autosomal dominant polycystic kidney disease constitutes the most prevalent hereditary kidney disease, associated with high rates of morbidity leading eventually to end-stage renal disease. Tolvaptan is a selective vasopressin antagonist and has emerged as a promising therapeutic option for patients with autosomal dominant polycystic kidney disease. The present review summarized current evidence regarding the safety profile of tolvaptan in patients with the disease. Consistent with its pharmacological action, aquaretic adverse events represent the most common side effects of tolvaptan, consisting of polyuria, pollakiuria and polydipsia. Gradual dose titration based on urinary osmolality, as well as dietary interventions aiming to reduce solute excretion, have been proposed as potential strategies to mitigate polyuria. In addition, tolvaptan administration may be complicated by liver injury, characterized by alanine aminotransferase and bilirubin elevations. Hepatotoxicity has been suggested to be triggered by impaired biliary clearance, activation of innate immunity and increased oxidative stress. Frequent monitoring of liver function tests has been shown to be effective in preventing Hy’s Law and liver failure cases. Uric acid elevation due to reduced renal excretion may lead to hyperuricemia and gout, although no drug discontinuations have been linked to these events. Future studies should confirm the safety profile of tolvaptan in large-scale real-world studies, clarify the pathogenetic pathways leading to hepatotoxicity and define its role in special populations, especially pediatric patients.