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The objective of this review was to answer the global prevalence of premature ovarian insufficiency (POI), and explore the associated factors including etiopathology and regions with POI.The search was conducted on reports from a total of eight databases that comprised Chinese National Knowledge Infrastructure (CNKI), Wanfang, China BioMedical Literature Database (CBM), PubMed, the Cochrane Library, Embase, Web of Science and Ovid MEDLINEThe results showed that the global overall prevalence of POI among women was 3.5%. By subgroup analysis, the prevalence of POI among women with iatrogenic etiology was 11.2%, followed by autoimmunity (10.5%); the prevalence of POI by region was 11.3% at the highest in North America followed by South America (5.4%); and the prevalence of POI was 5.3% in a developing country, higher than 3.1% in a developed country. The trend of prevalence of POI over the past 20 years was on the rise (althoughWe recommend that health and medical institutions strengthen public health awareness, achieve health-education goals related to POI and increase women's awareness of and attention to POI.

To study the cost-effectiveness of incorporating home semen analysis in screening for oligospermia and expediting time to evaluation.A decision analytic model was built using inputs from the medical literature. The index patient is the male partner in a couple seeking fertility, and entry into the model was assumed to be at the inception of the couple's attempts to conceive via natural means. Three main strategies are described and analyzed: (1) baseline strategy of no testing, (2) utilization of a home semen testing kit, (3) universal testing via a clinic visit and gold standard lab semen analysis. The primary outcome was detection of oligospermia (defined as sperm concentration15 million/mL). Strategies were ranked by months to evaluation by a male infertility specialist saved. Costs were considered from the patient perspective and were incorporated to determine the incremental cost per month saved to evaluation (ICMS) per 100,000 patients.Compared to a baseline strategy of no screening, utilizing a home test would save 89,000 months at the incremental cost of $7,418,000 for an ICMS of $45.51. Shifting to a strategy of universal gold standard clinic and lab testing saves an additional 3000 months but at an ICMS of $17,691 compared to the home testing strategy.Widespread adoption and the early usage of home semen analysis may be a cost-effective method of screening for oligospermia and facilitating further evaluation with an andrology specialist.

To examine the association between selective serotonin reuptake inhibitor (SSRI) use and semen quality.We performed a retrospective review of all men undergoing semen analysis (SA) for fertility evaluation from 2002-2020 at a single academic medical center. Men were excluded if they had prior exposure to spermatotoxic medications, clomiphene citrate, gonadotropins, selective estrogen receptor modulators, or medical conditions known to impact male fertility. SSRI exposure was defined by an outpatient prescription within 90 days prior to any semen test. Differences between men with and without SSRI exposure were assessed with Wilcoxon rank sum for continuous variables and chi-squared testing for proportions. Univariable and multivariable linear regression models were fit to evaluate the relationship between SSRI use and individual semen parameters, controlling for age at the time of the semen analysis and non-SSRI drug use.A total of 8861 men were identified, of whom 153 men (1.7%) were exposed to SSRIs prior to SA. Median age was 35 years (interquartile range: 32-39) and was similar between groups (P = .999). Non-SSRI medication use was significantly higher in men taking SSRIs (78.4% vs 23.3%,.001). On univariable and multivariable analyses, SSRI exposure was not associated with differences in semen volume, sperm concentration, motility, total motile sperm count, or normal morphology.In adult men undergoing fertility evaluation, SSRI exposure was not associated with impaired semen parameters. These data may help inform reproductive counseling and medical decision-making regarding SSRI use in men seeking paternity.

Objective To examine infertility-related fund-raising campaigns on a popular crowdfunding website and to compare campaign characteristics across states with and without legislative mandates for insurance coverage for infertility-related care. Design Retrospective cohort study. Setting Online crowdfunding platform (GoFundMe) between 2010 and 2020. Patient(s) GoFundMe campaigns in the United States containing the keywords “fertility” and “infertility.” Intervention(s) State insurance mandates for infertility treatment coverage. Main Outcome Measure(s) Primary outcomes included fund-raising goals, funds raised, campaign location, and campaigns per capita. Result(s) Of the 3,332 infertility-related campaigns analyzed, a total goal of $52.6 million was requested, with $22.5 million (42.8%) successfully raised. The average goal was $18,639 (standard deviation [SD] $32,904), and the average amount raised was $6,759 (SD $14,270). States with insurance mandates for infertility coverage had fewer crowdfunding campaigns per capita (0.75 vs. 1.15 campaigns per 100,000 population than states without insurance mandates. Conclusion(s) We found a large number of campaigns requesting financial assistance for costs associated with infertility care, indicating a substantial unmet financial burden. States with insurance mandates had fewer campaigns per capita, suggesting that mandates are effective in mitigating this financial burden. These data can inform future health policy legislation on the state and federal levels to assist with the financial burden of infertility.

The characteristics of men who use direct-to-consumer (DTC) men's health services are not well understood. We conducted an online survey of adult men via ResearchMatch, assessing sociodemographic data, health behaviors, and concern for low testosterone and infertility. Logistic regression estimated the association between participant characteristics and familiarity with and reported use of DTC services such as Hims® and Roman®. Among 1276 men surveyed, 62.2% were concerned about low testosterone. While almost half (48.5%) were familiar with men's DTC health services, only 37 (2.9%) reported using these services. On multivariable analysis, men who used DTC men's health services were more likely to be younger (age 18-39: odds ratio [OR] 2.94, 95% confidence interval [CI] 1.03-8.38, p = 0.04; age 40-59: OR 3.26, CI 1.17-9.10, p = 0.02; referent age ≥60), have annual income between $75k and $100k (OR 5.25, CI 1.39-19.87.45, p = 0.02), and be concerned about low testosterone (OR 3.81, CI 1.46-9.96, p = 0.01). In conclusion, younger men and those with mid-range incomes were more likely to use online DTC men's health services compared to older or wealthier men. Likewise, men with concerns about low testosterone were more likely to use DTC services, but other health-conscious behaviors and frequency of doctor visits did not predict use.

The influence of local thinning thickness defects on the buckling of cylindrical shells is investigated. A static buckling model of cylindrical shells with defects is established based on the Hamil...

Four azoles with similar element percentages but different heterocyclic rings and functional groups are investigated with fs laser-induced breakdown spectroscopy (LIBS) as regards the influence of the interaction between the functional groups and heterocyclic rings on laser-induced plasma (LIP) emission. Temporally and spatially resolved measurements of the CN and C2 emissions are obtained and analyzed. The functional group affects the π-electron delocalization of the heterocyclic ring and consequently changes the dissociation pathways of the heterocyclic ring. At the early stage, CN is formed from the atomic recombination or native fragments, while at the late stage, through the remaining native fragments. In the whole plasma lifetime, C2 is mainly transformed from CN. Furthermore, dynamic CN and C2 distributions mediated by the laser-induced shock waves are discussed.

Based on the Reissner shell theory and a new symplectic method, an analytical exact solution approach is presented in this paper to deal with free vibration of stepped cylindrical shells with thickness variations in both the axial and circumferential directions. Such cylindrical shells are often applied for designing aeronautics and space structures and hence any local defects and local geometric variations will result in significant design consequences. For this reason, this paper intends to establish a cylindrical shell model with local wall defects including local wall thinning and wall thickness stepped variations. A new exact solution approach for free vibration of the model are obtained by superposing the eigensolutions of the perfect shell. To ensure validity of the present result and the universality of the method, the solutions for three forms of stepped shells are compared with published data and finite element analysis. The effects of geometric parameters of the local thinning defect on free vibration characteristics are also investigated and presented.

To assess the reliability of peer-review of TURBT videos as a means to evaluate surgeon skill and its relationship to detrusor sampling.Urologists from an academic health system submitted TURBT videos in 2019. Ten blinded peers evaluated each surgeon's performance using a 10-item scoring instrument to quantify surgeon skill. Normalized composite skill scores for each surgeon were calculated using peer ratings. For surgeons submitting videos, we retrospectively reviewed all TURBT pathology results (2018-2019) to assess surgeon-specific detrusor sampling. A hierarchical logistic regression model was fit to evaluate the association between skill and detrusor sampling, adjusting for patient and surgeon factors.Surgeon skill scores and detrusor sampling rates were determined for 13 surgeons performing 245 TURBTs. Skill scores varied from -6.0 to 5.1 [mean: 0; standard deviation (SD): 2.40]. Muscle was sampled in 72% of cases, varying considerably across surgeons (mean: 64.5%; SD: 30.7%). Among 8 surgeons performing5 TURBTs during the study period, adjusted detrusor sampling rate was associated with sending separate deep specimens (odds ratio [OR]: 1.97; 95% confidence interval [CI]: 1.02-3.81, P = .045) but not skill (OR: 0.81; 95% CI: 0.57-1.17, P = .191).Surgeon skill was not associated with detrusor sampling, suggesting there may be other drivers of variability of detrusor sampling in TURBT.

Aid of a metallic overlayer to nickel/yttrium-stabilized-zirconia (Ni/YSZ) anode is investigated in Direct Methane Fuel Cell. Copper modified nickel metallic overlayer shows high activity for fuel cell performance and good stability to coking in methane atmosphere. The copper-nickel overlayer provides advantages of material compatibility with the substrate and catalytic function on copper-modified nickel sites. The results suggest that the overlayer is effective for decomposition of methane and tolerant to coking by removal of deposited carbon via oxidation and gasification reaction.

Digital elevation model (DEM) is an important geospatial data, which can provide a lot of topographic information. Currently, most commonly DEM data is derived from SAR images acquired before 2011, which has poor timeliness and is difficult to reflect the latest topographic features in many areas, especially in urban areas where the topographic features are rapidly updated. Therefore, it is necessary to explore DEM generation methods in urban areas to provide technical support for further studies on municipal planning and surface deformation in urban areas.This paper used two SAR images with bistatic mode, single-polarization (HH), and single look complex as experimental data from TerraSAR-X/TanDEM-X. The imaging time was January 30, 2013. The spatial baseline was 248.467 m. The research obtained good timeliness and high-resolution DEM of Maanshan area based on the iteration and fusion technology using two TerraSAR-X/Tandem-X SAR images and AW3D30 DEM from JAXA/EORC.With a comparison of 90m SRTM and 30 m AW3D30, this paper found that the DEM based on iteration and fusion technology could show more ground details, especially for the large single buildings at the sparse area. However, the extracted DEM at the dense-buildings area had the low reliability and still needed to further explore the solution, due to the obstruct of sensor line of sight and the distribution of shadow.In conclusion, this paper confirmed that it is feasible to obtain high-resolution and high time efficiency DEM using the iteration and fusion technology. It is able to improve the resolution of DEM and update the topographic from the original DEM by iteratively fused with AW3D30 to eliminate overlay and shadow.

This study examined the relationship between stimulant medications used for the treatment of attention deficit hyperactivity disorder and semen parameters. We performed a retrospective cohort study at a large, academic institution between 2002 and 2020. We included men with a semen analysis without prior spermatotoxic medication use, empiric medical therapy exposure or confounding medical diagnoses (varicocele, Klinefelter’s syndrome, cryptorchidism, cystic fibrosis, diabetes, cancer or cancer-related treatment, and azoospermia). Men were stratified by stimulant exposure (methylphenidate or amphetamines). A multivariable linear regression was fit to assess the association between individual semen parameters, age, stimulant exposure and non-stimulant medication use. Of 8,861 men identified, 106 men had active prescriptions for stimulants within 90 days prior to semen testing. After controlling for age and exposure to non-stimulant medications, stimulant use was associated with decreased total motile sperm count (β: −18.00 mil/ejaculate and standard error: 8.44, p = 0.033) in the setting of decreased semen volume (β: −0.35 ml, and standard error: 0.16, p = 0.035), but not sperm concentration, motility and morphology. These findings suggest a role for reproductive physicians and mental health providers to consider counselling men on the potential negative impact of stimulants prescribed for attention deficit hyperactivity disorder on semen volume during fertility planning.

免疫治疗与传统的肿瘤治疗方式相比具有更大的优势，在一些难治的癌症以及晚期癌症患者中取得了令人鼓舞的效果和良好预后，但在患者中的响应率不高。在肿瘤发展过程中，免疫系统与肿瘤相互作用过程称为肿瘤免疫编辑，并进一步细分为免疫清除、免疫平衡、免疫逃逸3个阶段。本文概述了肿瘤免疫编辑3个阶段中肿瘤微环境的变化，研究这些变化，对解决免疫治疗抗性，针对性用药设计以及联合用药方案都具有重要意义。.

蛋白酶激活受体2（protease activated receptor 2，PAR2）是G蛋白耦联受体超家族的成员，广泛表达于肠上皮细胞中。在结直肠癌的肿瘤微环境中，存在着多种蛋白酶，可以激活肿瘤细胞或间质细胞中的PAR2，从而调控肿瘤细胞的行为。在本综述中，作者关注于PAR2在结直肠癌发生发展过程中调控的信号通路，对PAR2的作用机制展开阐述。.

INTRODUCTION AND OBJECTIVE:Prior work has shown that detrusor muscle sampling (MS) from transurethral resection of bladder tumor (TURBT) is related to oncologic outcomes. It is unknown if surgeon s...

INTRODUCTION AND OBJECTIVE:Recent work shows that reproductive endocrinologists (REI) are the primary referral base for reproductive urologists; however, many men with infertility do not undergo fe...

INTRODUCTION AND OBJECTIVE:Transperineal (TP) biopsy and adoption of magnetic resonance imaging (MRI) prior to biopsy are both increasingly utilized. Few studies have examined the cost-effectivenes...

在结直肠普通型腺瘤、锯齿状病变/息肉、炎性病变相关性息肉和错构瘤性息肉系列介绍的基础上，进一步对结直肠炎症性肠病相关性良性病变和息肉病进行阐述。结合原来分类，根据病变的组织形态学、发生机制和相关遗传学特征不同，建议将结直肠非浸润性上皮性病变分为6类病理组织学类型。对异型增生、上皮内瘤变和黏膜内癌的相关概念及进展进行讨论。.

BackgroundGenome-wide association studies have been conducted in alcohol use disorder (AUD), and they permit the use of polygenic risk scores (PRSs), in combination with clinical variables, to predict the onset of AUD in vulnerable populations.MethodsA total of 2794 adolescent/young adult subjects from the Collaborative Study on the Genetics of Alcoholism were followed, with clinical assessments every 2 years. Subjects were genotyped using a genome-wide chip. Separate PRS analyses were performed for subjects of European ancestry and African ancestry. Age of onset of DSM-5 AUD was evaluated using the Cox proportional hazard model. Predictive power was assessed using receiver operating characteristic curves and by analysis of the distribution of PRS.ResultsEuropean ancestry subjects with higher than median PRSs were at greater risk for onset of AUD than subjects with lower than median PRSs (p= 3× 10-7). Area under the curve for the receiver operating characteristic analysis peaked at 0.88 to 0.95 using PRS plus sex, family history, comorbid disorders, age at first drink, and peer drinking; predictive power was primarily driven by clinical variables. In this high-risk sample, European ancestry subjects with a PRS score in the highest quartile showed a 72% risk for developing AUD and a 35% risk of developing severe AUD (compared with risks of 54% and 16%, respectively, in the lowest quartile).ConclusionsPredictive power for PRSs in the extremes of the distribution suggests that these may have future clinical utility. Uncertainties in interpretation at the individual level still preclude current application.

To determine whether health-conscious men are more likely to be concerned about infertility and self-initiate semen analysis at a laboratory/clinic or through a direct-to-consumer at-home product without a health care provider recommendation.Cross-sectional survey conducted online via ResearchMatch.org between November 2019 and January 2020. Men age 18 and older without children (n = 634) were included for analysis. Outcomes were likelihood of self-initiating a semen analysis, prevalence of infertility concern.Of the 634 participants, 186 expressed concern about infertility but only 29% were likely to discuss these concerns with a health care provider. More men would self-initiate a semen analysis using an at-home product than through a traditional laboratory/clinic (14.2% vs 10.4%, P = .04). Odds of self-initiating a traditional semen analysis were higher for men concerned about low testosterone (odds ratio [OR] 2.30, 95% confidence interval [CI] 1.12-4.74, P = .023) and infertility (OR 3.91, 95% CI 2.14-7.15, P.001). Self-initiating an at-home semen analysis was associated with concern for low testosterone and infertility as well as middle age (age 40-59: OR 3.02, 95% CI 1.16-7.88, P = .024) and fitness tracker use (OR: 1.95, 95% CI 1.12-3.39, P = .018).Many men were unlikely to discuss infertility concerns with a health care provider. Middle aged men and those who used fitness trackers were more likely to self-initiate fertility evaluation through at-home semen analysis. Concern about low serum testosterone was pervasive and strongly associated with concern for being infertile and self-initiating a semen analysis of any kind.

SUMMARYFrontotemporal dementia (FTD) due to MAPT mutation causes pathological accumulation of tau and glutamatergic cortical neuronal death by unknown mechanisms. We used human induced pluripotent stem cell (iPSC)-derived cerebral organoids expressing tau-V337M and isogenic corrected controls to discover early alterations due to the mutation that precede neurodegeneration. At 2 months, mutant organoids show upregulated expression of MAPT, and glutamatergic signaling pathways and regulators including the RNA-binding protein ELAVL4. Over the following 4 months, mutant organoids accumulate splicing changes, disruption of autophagy function and build-up of tau and P-tau S396. By 6 months, tau-V337M organoids show specific loss of glutamatergic neurons of layers affected in patients. Mutant neurons are susceptible to glutamate toxicity which was rescued pharmacologically by treatment with the PIKFYVE kinase inhibitor apilimod. Our results demonstrate a sequence of events that precede cell death, revealing molecular pathways associated with glutamate signaling as potential targets for therapeutic intervention in FTD.