Objective: Although life stress and adversity have emerged as risk factors for mental health problems and cognitive impairment among older adults, prior studies on this topic have been cross-sectional and based on relatively homogeneous samples. To address these issues, we examined prospective associations between lifetime adversity and symptoms of depression, anxiety, and cognitive impairment in a nationally representative, longitudinal sample of older adults in the U.S. Method: We analyzed data from the Health and Retirement Study (1992-2016). The sample included 3,496 individuals (59.9% female), aged ≥64 years old (M age=76.0 ±7.6 years). We used the individual-level panel data and ordinary least squares regressions to estimate associations between childhood and adulthood adversities and later-life depression, anxiety, and cognitive impairment. Results: Many participants experienced a significant early life (38%) or adulthood (79%) stressor. Second, experiencing a childhood adversity was associated with a 17.4% increased risk of experiencing an adulthood adversity. Finally, childhood and adulthood adversities both prospectively predicted more symptoms of late-life depression, anxiety, and cognitive impairment. Discussion: These findings are among the first to demonstrate prospective associations between lifetime adversity and symptoms of depression, anxiety, and cognitive impairment in older adults. Screening for lifetime stressors may thus help health care professionals and policymakers identify individuals who could benefit from interventions designed to reduce stress and enhance resilience.

Background: Patients with attention-deficit/hyperactivity disorder (ADHD) and patients with borderline personality disorder (BPD) show symptomatic overlaps. They both suffer from deficits in emotional regulation, are impulsive and have problems with their self-concept. Therefore, a precise diagnostic differentiation is of great importance. The aim of this study was to find symptom overlaps and differences in patients with ADHD and BPD. Methods: 80 patients with ADHD, 55 patients with BPD and 55 healthy controls were examined regarding their ADHD and BPD symptoms and their degree of emotional dysregulation using self-report instruments. Results: Patients with ADHD and patients with BPD did not differ significantly in their expression of emotional dysregulation. However, the ADHD patients showed higher scores in impulsivity, inattention, and hyperactivity, whereas the group with BPD showed higher scores in self-concept problems and suicidal behaviour. The two clinical groups showed significantly higher scores in emotional dysregulation and all other symptom domains compared to the control group. Conclusion: The symptom overlap in emotional dysregulation yields implications for both further research and diagnosis of ADHD. Further studies should define emotional dysregulation consistently in order to examine the same construct.

This study examined possible impact of social support on food insecurity in South Africa’s Soshanguve township. Binomial logit models, combine statistical and maximum likelihood features to estimate odds of household food insecurity in Soshanguve, adjusted separately for gender and employment of household head. Predictably, economic factors are weakly associated with increased risk of general food insecurity at lower household incomes, with large families, the unemployed, and those with lower education. Social support, in the form of access to child and/or pension grant or special relief of COVID distress, has no significant impact on food insecurity, neither is receiving in-kind help. The study is interdisciplinary and contributes to the understanding of the link between COVID-19 pandemic, and the attainment of United Nations sustainable development goals (SDGs) through urban metabolic flows, and the relationships between physical, social and economic factors in the urban environment.

Carbon nanotubes are excellent candidates for the development of nano-reinforced polymer composite materials. However, assurance of homogeneous dispersion, interfacial compatibility between the carbon nanotube and the polymer, and exfoliation of the aggregates of carbon nanotubes, are required for the successful integration of carbon nanotubes into nanocomposites. The present study is focused primarily upon the electrical and mechanical properties of catalytically-grown multi-walled carbon nanotube-reinforced epoxy composite materials. Particular emphasis is placed upon the effect of carbon loading on the electrical conductivity and the influence of temperature on the loss factor and modulus for the composite materials. The results indicate that the electrical properties of the composite would not be changed from those of the bulk polymer until the average distance between the carbon nanotubes is reduced such that either electron tunneling through the polymer or physical contacts may be formed. Among the challenges introduced in the fabrication of carbon nanotube-filled polymer composites is the necessity to creatively control and make use of surface interactions between carbon nanotubes and polymeric chains in order to obtain an adequate dispersion throughout the matrix without destroying the integrity of the carbon nanotubes. Frequency domain material properties are therefore limited to applications where strains are small and stress is approximately linear with strain and the strain rate. Frequency domain material properties become irrelevant if the material exhibits nonlinear elastic behavior or is subjected to large strains. Depending on the type of polymers in the matrix, above a certain temperature limit, degradation starts or cross-linking starts. The deformed elastic body possess an amount of potential energy equal to the initial amount of potential energy minus the amount of energy irreversibly dissipated. The modulus and loss factor variables of a damping material are highly dependent upon the temperature of the damping material and the vibration frequency. Because of their viscoelastic nature, the stress and strain in viscoelastic materials are not in phase, and, in fact, exhibit hysteresis. The resonant frequency is related to the modulus of the catalytically-grown multi-walled carbon nanotube-reinforced epoxy composite.Keywords: Composite materials; Electrical properties; Mechanical properties; Carbon nanotubes; Electrical conductivity; Loss modulus

Background and Purpose: PARP and HDAC inhibitors are approved for the clinical treatment of malignancies, but acquired resistance or limited effects on solid tumors with single-agent present challenges. Therefore, there is an urgent need to design and synthesis of dual inhibitors involving a different mechanism of action can provide new treatments. Experimental Approach: We validate the correlation and synergy between PARP and HDAC by database analysis and colony formation assay. Novel dual PARP and HDAC inhibitors antitumor effects in vitro were validated by flow cytometry and cell biology analysis. Pharmacological characterization was characterized by enzymatic inhibition assays, cell viability assays, western blot, real-time PCR, immunofluorescence analyses. The antitumor effect in vivo was validated in MDA-MB-436 and 4T1 xenograft mouse models. Key Results: Bioinformatics analyses and a combination of experiments demonstrate the synergistic effects of PARP and HDAC inhibitors in triple-negative breast cancer. Novel dual PARP and HDAC inhibitors were rationally designed and synthesized, and exhibited high enzyme inhibition activity, showing excellent antitumor effects in vitro and in vivo. Mechanistically, dual PARP and HDAC inhibitors significantly induced BRCAness to restore synthetic lethality and the accumulation of cytosolic DNA to activate the cGAS–STING pathway and produce proinflammatory chemokines through type Ⅰ IFN-mediated JAK–STAT signaling. Moreover, these inhibitors promoted neoantigen generation and upregulated antigen presentation genes and PD-L1. Conclusion and Implications: Novel dual PARP and HDAC inhibitors showing excellent antitumor effect via the activation of the tumoral IFN signaling and cytokine production to enhance the immune response for triple-negative breast cancer.

Carnivores participate in forest disturbance recovery by dispersing the seeds that pass through their digestive systems. The objective of this study was to evaluate the capacity of mammals for Juniperus deppeana seed dispersal with an experimental evaluation of endozoochory and diploendozoochory, through indices of recovery, viability, changes in testas, and retention of seeds in the digestive tract. Juniperus deppeana fruits were collected in the Sierra Fría Natural Protected Area, Aguascalientes, Mexico, and were administered in the diet of gray fox (Urocyon cinereoargenteus), coati (Nasua narica) and domestic rabbits (Oryctolagus cuniculus) these three mammals represented the endozoochory. For the diploendozoochory, seeds excreted by rabbits were incorporated into the diets of bobcat (Lynx rufus) and cougar (Puma concolor) in a local zoo. The seeds present in the scats were collected, and recovery rates and retention times were estimated; viability was estimated by X-ray optical densitometry, and testa thicknesses and surfaces were checked by scanning electron microscopy. The results showed a recovery of seeds greater than 70% in all the animals; the retention time was < 24 h in the endozoochory, but the time was longer (24-96 h) in the diploendozoochory (P < 0.05). Seed viability (x ̵̅ ± SD) was decreased in rabbits (74.0 ± 11.5 %) compared to fruits obtained directly from the canopy (89.7 ± 2.0 %), while gray fox, coati, bobcat and puma did not affect viability (P < 0.05). An increase in the thickness of the testas was also observed in seeds excreted from all mammals (P < 0.05). Through evaluation, our results suggest that mammalian endozoochory and diploendozoochory contribute to dispersal of J. deppeana by maintaining viable seeds with adaptive characteristics in the testa to promote resilience and forest restoration. In particular, felines (predators) can provide an ecosystem service through scarification and seed dispersal.

Background: Intrapartum decision-making for women with a previous caesarean section (CS) is complex due to competing risks of trial of labour after cesarean (TOLAC) and elective repeat CS (ERCS). Objective: Determine rates of TOLAC and vaginal birth after cesarean (VBAC) in sub-Saharan Africa (SSA) and estimate rates of adverse events associated with TOLAC versus ERCS. Search Strategy: We searched PubMed, MEDLINE, CAB, EMBASE, and African-specific databases. Selection Criteria: We included studies with at least one previous CS conducted in SSA. Data Collection and Analysis: We extracted data on study design, planned and actual delivery mode, and maternal and perinatal outcomes. We calculated median TOLAC and VBAC rates pooled mean uterine rupture rate and compared uterine rupture rates and mortality between TOLAC and ERCS. Main Results: From 51 included studies, the median TOLAC and VBAC rates, weighted for sample size, were 75% (IQR: 40-100%) and 34% (IQR: 24-44%) , respectively; and the weighted mean uterine rupture rate was 1.3% (SD: 1.6%). The uterine rupture rate [1.2% vs 0.2%, OR 1.54 (95% CI 0.63-3.75)] and maternal mortality [0.3% vs <0.1%, OR 0.77 (95% CI 0.30-1.98)] did not differ significantly between TOLAC and ERCS groups, respectively, however perinatal mortality was higher for the TOLAC group (5% vs 1%, OR 3.3 ; 95% CI 1.5-6.9) Conclusions: We found high rates of TOLAC and moderate rates of VBAC across SSA, with a perinatal but no maternal benefit to ERCS compared to TOLAC. Further research is needed to understand delivery outcomes in this population of women.

In this work, we study the inverse problem of finding the initial condition for one-dimensional Burgers' equation from the interior observation. Using the variational method, the inverse problem is reformulated as a optimal control problem. The necessary optimality condition will be calculated. We also use the conjugate gradient method to find the minimum of objective functional.

Objective: to investigate progressive muscle relaxation exercises and relaxation music on the severity of restless legs syndrome (RLS) and sleep quality in pregnant women. Design: Randomized clinical trial. Setting: A university clinic in Turkey. Population: 67 pregnant women with RLS. Methods: Participants were allocated into three groups; the control group, progressive muscle relaxation (PMR) group and relaxation music (RM) group. The PMR and RM programs were explained toall participants, and the first program was tested under the supervision of the researcher. PMR and RM group participants performed the program daily throughout 4 weeks. Severity of RLS with the International Restless Leg Syndrome Scale (IRLSS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI) were assessed at baseline, 2 and 4 weeks for all the groups. Results: The groups were similar in terms of demographic and clinical characteristics, as well as IRLSS and PSQI scores at baseline. The PMR and RM groups showed significant improvement in terms of IRLSS (severity of RLS) score; the PMR group, however, experienced better alleviation in IRLSS score than the RM group. The PMR and RM groups showed significant improvement in terms of PSQI (sleep quality) score; however, there was no statistical difference, when PMR compared to RM group. Conclusion: PMR and also RM as complementary therapies could be used to alleviate the severity of RLS and improve sleep quality during pregnancy. PMR have better improvement in alleviating the severity of RLS.

Objective: The study was conducted to know the impact of COVID-19 vaccination on menstrual cycle patterns, pre- and post-menstrual symptoms in women aged 18-45 years. Design & Setting: Multicentric observational study conducted in six institutes of national importance in different states of India over one year. Population: A total of 5709 female participants fulfilling inclusion criteria were enrolled. Methods: Data about impact of vaccines (COVISHIELD and COVAXIN) and prior COVID-19 infection on menstrual cycle and its associated symptoms were obtained using an online and offline survey. Main Outcome: COVID-19 vaccination with COVISHILED/COVAXIN resulted in menstrual cycle disturbances. Results: Of 5709 participants, 78.2% received COVISHIELD, 21.8% COVAXIN. Of all, 333(5.8%) developed post-vaccination menstrual disturbances with 32.7% frequent cycles, 63.7% prolonged cycles, and 3.6% inter-menstrual bleed. 301 participants, noticed changes in the amount of bleeding, with 50.2% excessive, 48.8% scanty, and 0.99% amenorrhea followed by heavy bleeding. Furthermore, the irregularities of menstrual cycle (p=0.011) and length (0.001) were significantly higher in the COVAXIN group (7.2%) as compared to COVISHIELD (5.3%). A total of 721 participants complained of newly developed/worsening pre- and post-menstrual symptoms. These symptoms were significantly higher in COVISHIELD group (p=0.031) with generalized weakness and body pains as main complaints (p=0.001). No significant difference was observed in COVID-19 infection incidence with these vaccines. When comparing menstrual abnormalities among those with COVID-19 infection, no significant associations were observed (p >0.05). Conclusions: COVISHILED and COVAXIN resulted in menstrual cycle disturbances and pre-and post-menstrual symptoms. The menstrual irregularities were significantly higher with COVAXIN vaccine.

Background: The role of early diagnosis of fetal cardiac abnormalities (both structural and functional) on the postnatal outcome has been controversial in literature for decade. Our objective was to evaluate the role of fetal echocardiography (FE) as a diagnostic tool for early detection of fetal cardiac abnormalities and its appropriate management plan. Results: This is a cross-sectional analytical and descriptive study that included 4366 singleton pregnant women (4366 fetuses) referred for FE from 2014 to 2022. Indications for referral and perinatal risk factors were documented. FE and postnatal transthoracic echocardiography were done. Maximum number of fetal echo done for the indication of presence of ICEF (1538, 35.2%). Routine FE done in 1199 (27.5%) individual. In 501(11.5%) individual had bad obstetric history. Fetal cardiac abnormalities were detected in 175 fetuses (4%). CHDs in 149 (3.4%), fetal arrhythmia in 17 (0.4%)cardiomyopathy in 3 (0.07%) fetuses and cardiac mass (Rhabdomyoma) in 6 fetuses (0.14%). Of the structural CHDs, maximum number of cases were large VSD, found in 24 (13.7%) cases, Four cases with tiny muscular ventricular septal defects and two cases with coarctation of aorta, one case of TGA with IVS and one case of large VSD were missed by FE and were diagnosed postnatal. Six cases of critical congenital heart disease were underwent early lifesaving neonatal intervention. Conclusions: FE can accurately diagnose most of the cardiac anomalies though few errors remain challenging (aortic coarctation). It also offers a good chance for successful early life saving management of some types of cardiac lesions.

Objectives: To evaluate the predictive significance of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in the prognosis of high-grade endometrial carcinoma and to establish a novel predictive model. Design: A retrospective multicenter study. Setting: Fifteen hospitals of the Chinese Endometrial Carcinoma Consortium. Population: This study included 910 high-grade epithelial endometrial carcinoma patients from the multicenter who underwent initial surgical treatment between January 1, 2005, and December 31, 2019. Methods: Data was retrospectively obtained from the medical records and follow-up information of patients. Cox proportional hazard regression models were developed to predict the risk of recurrence and death at 3, 5, and 10 years, and the models were validated and calibrated. The area under the curve was used to measure the predictive performance of the model. Main outcomes measures: Disease-free survival and overall survival. Result: Platelet-lymphocyte ratio and neutrophil-lymphocyte ratio were risk factors for recurrence, and neutrophil-lymphocyte ratio was a risk factor for death. We established models for predicting death and recurrence. In the validation cohort, the area under receiver operating characteristic curve of disease-free survival model at 3,5 and 10 years was 0.72, 0.77, 0.77, and of overall survival model was 0.72, 0.81, and 0.84. Kaplan–Meier survival analysis showed a significant difference between low-risk and high-risk groups. Conclusions: Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are risk factors affecting the prognosis of high-grade endometrial carcinoma patients. This novel prediction model for high-grade endometrial carcinoma can provide accurate postoperative risk classification and prognosis prediction for patients. Keywords: Endometrial carcinoma, prognostic model, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio

Background: The vein of Marshall ethanol infusion (VOM-EI) provides an opportunity to achieve bidirectional conduction block of mitral isthmus. However, this technique may induce traumatic pericarditis. There is a lack of research on which populations are prone to pericarditis after VOM-EI and how to treat it more effectively. Methods: This retrospective study included 77 consecutive patients who voluntarily underwent persistent atrial fibrillation radiofrequency ablation combined with VOM-EI. With the occurrence of postoperative pericarditis as the end point, the characteristics and risk factors of postoperative pericarditis were analyzed. The curative effect was evaluated by the symptom relief rate of pericarditis 48 hours after treatment. Results: 15 had postoperative pericarditis among the 77 patients, accounting for 19.5%. The hospital stay of the patients with pericarditis was longer than that without pericarditis (10.0 vs 8.0 days, P = 0.045). Of the 15 patients with postoperative pericarditis, 8 received colchicine. Among the patients treated with colchicine, the average treatment intensity was 1.04 mg/d, 7 patients were relieved within 48 hours, and the symptomatic remission rate was 87.5%. Among the remaining 7 patients who did not receive colchicine, only 2 patients had symptomatic remission. Compared with the group without colchicine, the duration of symptoms was significantly shorter (27.88 vs 51.93 hours, P = 0.024). In the multivariate logistic regression analysis, colchicine was the only effective method to relieve the 48 hours symptoms of postoperative pericarditis ( OR =17.500, CI 1.223-250.4, P = 0.035). Conclusion: Postoperative pericarditis is one of the complications of VOM-EI, and colchicine may have a good short-term effect on it.

Objective: In the study, it was aimed to determine the effect of ice massage applied to SP6 point during labor on labor pain, labor comfort, labor duration, and anxiety. Design: A single blind, randomized controlled experimental trial Setting and Participants: 100 primiparas, 50 in the intervention group and 50 in the control group, with 4-5 cm cervical dilatations were included in the study. Ice massage was applied to the SP6 point of the pregnant women in the intervention group at 4-5 cm, 6-7 cm, and 8-9 cm dilatations during three contractions. Measurement Tools: The Pregnant Information Form, VAS, the Partograph Form, Childbirth Comfort Questionnaire (CCQ), and the State Anxiety Scale were used to collect data. Result: It was found that VAS scores of the pregnant women in the intervention group were significantly lower compared to the control group following the intervention at 4-5 cm, 6-7 cm, and 8-9 cm cervical dilatations (p=0.001, p=0.003, p<0.001, respectively). Total CCQ and comfort level scores of the pregnant women in the intervention group at 8-9 cm cervical dilatation were determined to be significantly higher compared to the control group (p=0.044,p=0.027, respectively). In addition, it was determined that as the anxiety levels of the pregnant women increased, their total comfort score decreased (p<0.05). Conclusions: It was found that ice application to SP6 point during stage 1 of childbirth decreased labor pain and provided positive comfort. Therefore, this method can be used as a safe and effective midwife intervention in childbirth.

Abstract Aim: Blood pressure-lowering treatment is beneficial for preventing cardiovascular disease risk among elderly patients. However, the most appropriate BP targets for elderly patients are controversial. Methods: We extracted the individual-level data of participants over 60 years from the SPRINT study and ACCORD study first and then conducted a meta-analysis of major adverse cardiovascular events (MACEs) and adverse events (hypotension and syncope) and renal outcomes across the SPRINT, STEP, and ACCORD BP trials, which included 18,806 participants over 60. Participants were randomized to receive standard BP treatment or intensive BP treatment. Results: In this meta-analysis, intensive treatment exhibited a nominal trend toward decreases in all-cause death (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.76-1.26; p=0.87) and cardiovascular mortality (HR: 0.77; 95%CI: 0.54-1.08; p=0.13). The incidence of MACEs (HR: 0.83; 95%CI: 0.74-0.94; p=0.003) and stroke (HR: 0.70; 95% CI: 0.56-0.88; p=0.002) was reduced. Intensive treatment had an inconspicuous effect on coronary disease (HR: 0.87; 95% CI: 0.69-1.10; p=0.24) and heart failure (HR: 0.70; 95%CI: 0.40-1.22; p=0.21). Intensive treatment increased the risk of hypotension (HR: 1.46; 95%CI: 1.12-1.91; p=0.006) and syncope (HR: 1.43; 95%CI: 1.06-1.93; p=0.02). Intensive treatment did not increase the risk of either impaired kidney function among patients with chronic kidney disease (CKD) (HR: 0.98; 95% CI: 0.41-2.34; p=0.96) or without CKD (HR: 1.77; 95%CI: 0.48-6.56; p=0.40) at baseline. Conclusions: Intensive BP goals reduced the incidence of MACEs and increased the risk of adverse events without significant mortality or renal outcome changes.

Symphysis-Fundus Measurement; the Human Factor

Background: Fear of hospitalization in addition to uncertainties about appropriate treatment at the beginning of COVID -19 pandemic may have affected the health and outcome of pregnant women. Lack of transportation, closed out -patient services, and lack of employment has directly linked to poor maternal and perinatal outcomes during nationwide lockdown. This study aimed to assess perinatal outcome during the first COVID-19 pandemic lockdown at BPKIHS. Methods: This is a Descriptive Cross- Sectional Study conducted in a tertiary care center in Eastern Nepal from 24th march 2020 to 23rd July 2020 during the first COVID- 19 lockdown. Poor perinatal outcomes: perinatal death, preterm delivery, intrauterine growth restriction, newborn admission, and different reasons for admission were analyzed using descriptive statistics. Results: There were a total of 2685 obstetric admissions and 2442 deliveries during the study period of 4 months. The perinatal death rate was 26.2 per 1000 births. One hundred and twenty- eight newborns required neonatal admission and prematurity was the most common cause. Mean age and gestational age of women with poor perinatal outcome were 27.16 ± 6.02 years and 36.38± 4.54 weeks respectively. Conclusions: Despite the availability of comprehensive Emergency Obstetric Care (CEOC) at our center, poor perinatal outcome is still high. Which was directly or indirectly affected by COVID-19 pandemic lockdown as there was closure of OPD services, elective surgery, and most importantly lack of transportation.

Ferroptosis, a cohering network integrating iron, amino acids, lipids, and redox chemicals together，is a unique regulated cell death (RCD). Iron overload, excessive reactive oxygen species (ROS), and lipid peroxidation all contribute to the onset of ferroptosis. In recent years, a growing body of evidence suggests that ferroptosis is associated with some female reproductive diseases. The purpose of our review is to give a brief description of ferroptosis activation mechanism and relationship to female reproductive diseases including infertility, pregnancy associated diseases and ovarian cancer.

Multiplication of weights may or may not be a practical biological solution (the hypotheses is that biological neurons do not have symmetric feedback and exact 32-bit multiplication). As an approximation of universal approximation theorem, bit-shift (which is a non-differentiable symbol) is proposed. There are two variants of this problem (both of which can be solved using backpropagation): First variant is addition of bit-shift with non-negative float (without subtraction); The second variant is addition and subtraction of integers (without float). So, combining these two, we get additive-shift of float. The accuracy of this version is only about 2% lesser than the original DNN. The idea is to try to avoid clock-cycles and make it easier to do inference almost at the speed of electricity in semiconductor (without memory or with relatively less memory). Another idea is to improve the ML-training and inference process so that they are compute-constrained.

This paper proposes a new cost criterion to enhance the precision of a zonotopic state estimator for discrete-time descriptor linear systems. Originally, the algorithm solves a minimum-trace problem involving zonotopes, whose evolution is given by an interval observer structure containing extra design matrices, called degrees of freedom. Although the minimization of trace yields explicit solutions, it does not necessarily imply minimization of volume, and thereby, the precision of the output zonotope cannot be improved effectively. The volume measure for zonotopes is computationally expensive and, when used as cost criterion, implies nonlinear optimization problems. Motivated by such issues, we here propose a minimum-radius criterion where the smallest box enclosing the output zonotope is minimized. The resulting optimization problem is nonlinear, but its convexity is exploited to yield an equivalent linear program. The effectiveness of our approach is illustrated over two numerical examples.

Objective: We aimed at discussing additional cuts, a common problem in cervical conization. Whether the doctor’s choice of additional cuts in conization surgery could reduce the occurrence of positive cone margin. Design: A retrospective study. Setting: First Affiliated Hospital of Dalian Medical University (Dalian, China). Population: 965 patients underwent cervical conization. Methods: Statistical analysis of patients’ pathological reports. Main outcome measures: The age, preoperative pathology, pathological results of conization, whether or not to make additional cuts, cone depth and cone volume were studied. Result: Of the 965 patients included, age, pathology result of conization, whether to make additional cuts, cone depth and cone volume, there were significant difference between positive and negative cone groups. Next, the Multivariable logistic regression analysis suggested that older age (OR,1.036; 95%CI, 1.017 to 1.054; p<0.001), the pathology result of conization was HSIL or cervical cancer (OR,13.203; 95%CI,6.024 to 28.936; p<0.001), additional cuts (OR, 2.480; 95%CI 1.608 to 3.826; p=0.01) and smaller cone depth (OR, 0.591; 95%CI, 0.362 to 0.965, p=0.036), these factors were the independent risk for the positive margin group. Conclusions: A certain proportion of additional cuts can be effectively excised the positive margin that cannot be cut in the initial conization. Moreover, choosing the appropriate cone size can maintain a low positive margin rate without additional cuts. Keywords: Additional cuts; Cone depth; Cone volume; Doctor’s habit; High-grade squamous intraepithelial lesion; Cervical cancer

In this paper, we study the optimal control of a discrete-time stochastic differential equation (SDE) of mean-field type, where the coefficients can depend on both a function of the law and the state of the process. We establish a new version of the maximum principle for discrete-time mean-field type stochastic optimal control problems. Moreover, the cost functional is also of the mean-field type. This maximum principle differs from the classical principle one since we introduce new discrete-time mean-field backward (matrix) stochastic equations. Based on the discrete-time mean-field backward stochastic equations where the adjoint equations turn out to be discrete backward SDEs with mean field, we obtain necessary first-order and sufficient optimality conditions for the stochastic discrete mean-field optimal control problem. To verify, we apply the result to production and consumption choice optimization problem.

Parkinson’s Disease (PD) and vitamin D share a unique link as Vitamin D deficiency (VDD) prevails in PD. Thus, an in-depth understanding of Vitamin D biology in PD might be crucial for therapeutic strategies emphasizing Vitamin D. Specifically, explicating the effect of VDD and genetic polymorphisms of vitamin D-associated genes in PD, like VDR (Vitamin D Receptor) or GC (Vitamin D Binding Protein), may aid the process along with polymorphisms of Vitamin D metabolizing genes (e.g., CYP2R1, CYP27A1) in PD. Literature review of single nucleotide polymorphisms (SNPs) related to Vitamin D levels [GC (GC1-rs7041, GC2-rs4588), CYP2R1, CYP24A1, CYP27B1] and Vitamin D function [VDR (FokI - rs2228570, ApaI - rs7976091, BsmI-rs1544410, TaqI-rs731236)] was conducted to explore their relationship with PD severity globally. Furthermore, the DisGeNET database was utilized to explore the gene-disease associations in PD, and STRING alongside Cytoscape was utilized to identify critical genes associated with PD. VDR-FokI polymorphism was reported to be significantly associated with PD in Hungarian, Chinese, and Japanese populations, whereas VDR-ApaI polymorphism was found to affect PD in the Iranian population. However, VDR-TaqI and BsmI polymorphisms had no significant association with PD severity. Conversely, GC1 polymorphisms reportedly affected Vitamin D levels without influencing the disease severity. CYP2R1 (excluding rs1993116) was also reportedly linked to clinical manifestations of PD. Genetic polymorphisms might cause VDD despite enough sunlight exposure and vitamin D-rich food intake, enhancing inflammation, and thereby influencing PD pathophysiology. Knowledge of the polymorphisms associated with vitamin D appears promising for developing new therapeutic strategies against PD.

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