Pathogenic variants in human DNA damage repair genes mostly arose after the latest human out-of-Africa migration.

Introduction: The DNA damage repair (DDR) system in human genome is pivotal in maintaining genomic integrity. Pathogenic variation (PV) in DDR genes impairs their function, leading to genome instability and increased susceptibility to diseases, especially cancer. Understanding the evolution origin and arising time of DDR PV is crucial for comprehending disease susceptibility in modern humans. Methods: We used big data approach to identify the PVs in DDR genes in modern humans. We mined multiple genomic databases derived from 251,214 modern humans of African and non-Africans. We compared the DDR PVs between African and non-African. We also mined the DDR PVs in the genomic data derived from 5,031 ancient humans. We used the DDR PVs from ancient humans as the intermediate to further the DDR PVs between African and non-African. Results and discussion: We identified 1,060 single-base DDR PVs across 77 DDR genes in modern humans of African and non-African. Direct comparison of the DDR PVs between African and non-African showed that 82.1% of the non-African PVs were not present in African. We further identified 397 single-base DDR PVs in 56 DDR genes in the 5,031 ancient humans dated between 45,045 and 100 years before present (BP) lived in Eurasian continent therefore the descendants of the latest out-of-Africa human migrants occurred 50,000-60,000 years ago. By referring to the ancient DDR PVs, we observed that 276 of the 397 (70.3%) ancient DDR PVs were exclusive in non-African, 106 (26.7%) were shared between non-African and African, and only 15 (3.8%) were exclusive in African. We further validated the distribution pattern by testing the PVs in BRCA and TP53, two of the important genes in genome stability maintenance, in African, non-African, and Ancient humans. Our study revealed that DDR PVs in modern humans mostly emerged after the latest out-of-Africa migration. The data provides a foundation to understand the evolutionary basis of disease susceptibility, in particular cancer, in modern humans.

Chronic stress induces wide-spread hyperalgesia: The involvement of spinal CCK1 receptors.

Chronic primary pain (CPP) occurs in the absence of tissue injury and includes temporomandibular disorders (TMD), fibromyalgia syndrome (FMS) and irritable bowel syndrome (IBS). CPP is commonly considered a stress-related chronic pain and often presents as wide-spread pain or comorbid pain conditions in different regions of the body. However, whether prolonged stress can directly result in the development of CPP comorbidity remains unclear. In the present study, we adapted a 21 day heterotypic stress paradigm in mice and examined whether chronic stress induced wide-spread hyperalgesia, modeling comorbid CPP in the clinic. We found that chronic stress induced anxiety- and depression-like behaviors, and resulted in long-lasting wide-spread hyperalgesia over several body regions such as the orofacial area, hindpaw, thigh, upper back and abdomen in female mice. We further found that the expression of cholecystokinin (CCK)1 receptors was significantly increased in the L4-L5 spinal dorsal horn of the female mice after 14 and 21 day heterotypic stress compared with the control animals. Intrathecal injection of the CCK1 receptor antagonist CR-1505 blocked pain hypersensitivity in the subcervical body including the upper back, thigh, hindpaw and abdomen. These findings suggest that the upregulation of spinal CCK1 receptors after chronic stress contributes to the central mechanisms underlying the development of wide-spread hyperalgesia, and may provide a potential and novel central target for clinical treatment of CPP.

Factors influencing the continuance intention of the women's health WeChat public account: an integrated model of UTAUT2 and HBM.

Background: Women's health WeChat public accounts play a crucial role in enhancing health literacy and fostering the development of healthy behaviors among women by disseminating women's health knowledge. Improving users' continuous usage behavior and retention rates for the women's health WeChat public account is vital for influencing the overall effectiveness of health communication on WeChat. Objective: This study aimed to construct a comprehensive model, delving into the key factors influencing women's continuance intention of the women's health public accounts from the perspectives of perceived health threats, individual abilities, and technological perceptions. The goal is to provide valuable insights for enhancing user stickiness and the effectiveness of health communication on WeChat public accounts. Method: An online survey was conducted among women receiving gynecological care at a certain hospital to gage their willingness for sustained use of the women's health WeChat public accounts. Through structural equation modeling, the study investigated the influencing factors on women's sustained intention to use the women's health WeChat public accounts. Results: The study included a total of 853 adult women. Among them, 241 (28.3%) women had followed women's health official accounts in the past but do not currently follow them, 240 (28.1%) women had followed women's health official accounts in the past and are still following them, and 372 (43.6%) women had never followed women's health official accounts. Currently, 240 women are still browsing women's health public accounts, 52 of whom read women's health public accounts every day, and most of them read women's health public accounts for 10-20 min at a time (100, 11.7%). The results of the structural equation model revealed that performance expectancy, social influence, hedonic motivation, habit, and e-health literacy had significantly positive effects on women's sustained intention to use public accounts (performance expectancy: ß = 0.341, p < 0.001; social influence: ß = 0.087, p = 0.047; hedonic motivation: ß = 0.119, p = 0.048; habit: ß = 0.102, p < 0.001; e-health literacy: ß = 0.158, p < 0.001). E-health literacy and self-efficacy indirectly influence sustained intention by affecting performance expectancy, effort expectancy, social influence, facilitating conditions, hedonic motivation, and habit. The effect sizes of e-health literacy on performance expectancy, effort expectancy, social influence, facilitating conditions, hedonic motivation, and habit were 0.244 (p < 0.001), 0.316 (p < 0.001), 0.188 (p < 0.001), 0.226(p < 0.001), 0.154 (p < 0.001), and 0.073 (p = 0.046). The effect sizes of self-efficacy on performance expectancy, effort expectancy, social influence, facilitating conditions, hedonic motivation, and habit were 0.502 (p < 0.001), 0.559 (p < 0.001), 0.454 (p < 0.001), 0.662 (p < 0.001), 0.707 (p < 0.001), and 0.682 (p < 0.001). Additionally, perceived severity and perceived susceptibility indirectly affected sustained intention by influencing performance expectancy and social influence. The effect sizes of perceived severity on performance expectancy and social influence were 0.223 (p < 0.001) and 0.146 (p < 0.001). The effect size of perceived susceptibility to social influence was 0.069 (p = 0.042). Conclusion: Users' e-health literacy, self-efficacy, perception of disease threat, and users' technological perceptions of the WeChat public accounts are critical factors influencing women's continuance intention of using the WeChat public accounts. Therefore, for female users, attention should be given to improving user experience and enhancing the professionalism and credibility of health information in public account design and promotion. Simultaneously, efforts should be made to strengthen users' health awareness and cultivate e-health literacy, ultimately promoting sustained attention and usage behavior among women toward health-focused public accounts.

Observation of dichotomic field-tunable electronic structure in twisted monolayer-bilayer graphene.

Twisted bilayer graphene (tBLG) provides a fascinating platform for engineering flat bands and inducing correlated phenomena. By designing the stacking architecture of graphene layers, twisted multilayer graphene can exhibit different symmetries with rich tunability. For example, in twisted monolayer-bilayer graphene (tMBG) which breaks the C2z symmetry, transport measurements reveal an asymmetric phase diagram under an out-of-plane electric field, exhibiting correlated insulating state and ferromagnetic state respectively when reversing the field direction. Revealing how the electronic structure evolves with electric field is critical for providing a better understanding of such asymmetric field-tunable properties. Here we report the experimental observation of field-tunable dichotomic electronic structure of tMBG by nanospot angle-resolved photoemission spectroscopy (NanoARPES) with operando gating. Interestingly, selective enhancement of the relative spectral weight contributions from monolayer and bilayer graphene is observed when switching the polarity of the bias voltage. Combining experimental results with theoretical calculations, the origin of such field-tunable electronic structure, resembling either tBLG or twisted double-bilayer graphene (tDBG), is attributed to the selectively enhanced contribution from different stacking graphene layers with a strong electron-hole asymmetry. Our work provides electronic structure insights for understanding the rich field-tunable physics of tMBG.

Pathogenic variants in human DNA damage repair genes mostly arose in recent human history.

BACKGROUND: Genome stability is maintained by the DNA damage repair (DDR) system composed of multiple DNA repair pathways of hundreds of genes. Germline pathogenic variation (PV) in DDR genes damages function of the affected DDR genes, leading to genome instability and high risk of diseases, in particular, cancer. Knowing evolutionary origin of the PVs in human DDR genes is essential to understand the etiology of human diseases. However, answer to the issue remains largely elusive. In this study, we analyzed evolutionary origin for the PVs in human DDR genes. METHODS: We identified 169 DDR genes by referring to various databases and identified PVs in the DDR genes of modern humans from ClinVar database. We performed a phylogenetic analysis to analyze the conservation of human DDR PVs in 100 vertebrates through cross-species genomic data comparison using the phyloFit program of the PHAST package and visualized the results using the GraphPad Prism software and the ggplot module. We identified DDR PVs from over 5000 ancient humans developed a database to host the DDR PVs ( https://genemutation.fhs.um.edu.mo/dbDDR-AncientHumans ). Using the PV data, we performed a molecular archeological analysis to compare the DDR PVs between modern humans and ancient humans. We analyzed evolution selection of DDR genes across 20 vertebrates using the CodeML in PAML for phylogenetic analysis. RESULTS: Our phylogenic analysis ruled out cross-species conservation as the origin of human DDR PVs. Our archeological approach identified rich DDR PVs shared between modern and ancient humans, which were mostly dated within the last 5000 years. We also observed similar pattern of quantitative PV distribution between modern and ancient humans. We further detected a set of ATM, BRCA2 and CHEK2 PVs shared between human and Neanderthals. CONCLUSIONS: Our study reveals that human DDR PVs mostly arose in recent human history. We propose that human high cancer risk caused by DDR PVs can be a by-product of human evolution.

Microfluidic particle counter visualizing mucosal antibodies against SARS-CoV-2 in the upper respiratory tract for rapid evaluation of immune protection.

Mucosal antibodies in the upper respiratory tract are the earliest and most critical responders to prevent respiratory infections, providing an indication for the rapid evaluation of immune protection. Here, we report a microfluidic particle counter that directly visualizes mucosal antibody levels in nasal mucus. The mucosal anti-SARS-CoV-2 spike receptor binding domain (RBD) antibodies in nasal secretions first react with magnetic microparticles (MMPs) and polystyrene microparticles (PMPs) that are surface-modified to form a "MMPs-anti-spike RBD IgG-PMPs" complex when RBD is present. After magnetic separation and loading into the microfluidic particle counter, the free PMPs, which are reduced with increasing anti-spike RBD IgG antibody levels, are trapped by a microfluidic particle dam and accumulate in the trapping channel. A sensitive mode [limit of detection (LOD): 14.0 ng mL-1; sample-to-answer time: 70 min] and an equipment-free rapid mode (LOD: 37.4 ng mL-1; sample-to-answer time: 20 min) were achieved. Eighty-seven nasal secretion (NS) samples from vaccinees were analyzed using our microfluidic particle counter, and the results closely resemble those of the gold-standard enzyme-linked immunosorbent assay (ELISA). The analysis shows that higher antibody levels were found in convalescent volunteers compared to noninfected volunteers. Together, we demonstrate a rapid kit that directly indicates immune status, which can guide vaccine strategy for individuals and the government.

Do serum vitamin D levels affect assisted reproductive outcomes and perinatal outcomes in young non-PCOS patients? A retrospective study.

PURPOSE: This study aimed to determine the influence of serum vitamin D levels on assisted reproductive and perinatal outcomes in young non-polycystic ovary syndrome (PCOS) patients. METHODS: A total of 3397 non-PCOS women under 35 years who underwent their first IVF/ICSI cycle at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University, from 2018 to 2019, were included. The women were categorized into two groups based on their serum 25(OH)D concentrations: deficient group [25(OH)D < 50 nmol/L] and non-deficient group [25(OH)D ≥ 50 nmol/L]. Ovulation induction results, clinical pregnancy rate, cumulative live birth rate (CLBR), and perinatal outcomes of both groups were compared. RESULTS: A total of 1113 non-PCOS women had successful pregnancies in their first completed IVF cycle. Comparison of laboratory results between the two groups revealed a significantly higher number of oocytes retrieved in the vitamin D-non-deficient group (15.2 ± 6.8 vs. 14.5 ± 6.7, p = 0.015). After controlling for confounding factors, there was no significant difference in the CLBR between the vitamin D-deficient group and the non-deficient group (71.0%, 1,973/2,778 vs. 69.0%, 427/619, p = 0.314, unadjusted). The prevalence of gestational diabetes mellitus (GDM) was higher in the vitamin D-deficient group than in the vitamin D-non-deficient group in both fresh-cycle singleton live births (3.8% vs. 1.2%) and twin live births (2.3% vs. 1.5%). CONCLUSION: This study demonstrated that vitamin D-deficient group had a lower number of oocytes retrieved than the non-deficient group and a higher prevalence of GDM, suggesting that vitamin D deficiency impacts assisted pregnancies and perinatal outcomes in infertile non-PCOS women. However, further studies are required to confirm these findings.

Thyroid-stimulating hormone levels are associated with estradiol levels and impact reproductive outcomes in preconceptionally euthyroid women undergoing their first IVF/ICSI cycles.

PURPOSE: Controlled ovarian hyperstimulation (COH) has been reported to affect thyroid function; however, the impact of thyroid-stimulating hormone (TSH) levels during COH on embryo development and early reproductive outcomes has largely not been determined. Therefore, the aim of the present study was to investigate whether TSH levels are associated with COH and impact early reproductive outcomes in preconceptionally euthyroid women. METHODS: This was a prospective cohort study. A total of 338 euthyroid women who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the gonadotropin releasing hormone agonist (GnRH-a) protocol were included. Samples were collected at different representative time points for TSH and estradiol measurements. RESULTS: TSH levels significantly increased with the administration of Gn and maintained this tendency until the trigger day. Basal TSH levels increased along with basal estradiol levels and remained stable when estradiol levels were higher than 150 pmol/L. On the trigger day, TSH levels changed with increasing estradiol levels in the high-normal basal TSH group but not in the low TSH group. TSH did not impact clinical pregnancy or early pregnancy loss after adjusting for age, stage or number of embryos. CONCLUSION(S): Serum TSH levels change significantly during COH and are associated with significant changes in estradiol levels. However, euthyroid women with high-normal TSH levels showed similar development potential for inseminated embryos and early reproductive outcomes compared to those with low TSH levels.

OGT and OGA: Sweet guardians of the genome.

The past 4 decades have witnessed tremendous efforts in deciphering the role of O-GlcNAcylation in a plethora of biological processes. Chemists and biologists have joined hand in hand in the sweet adventure to unravel this unique and universal yet uncharted post-translational modification, and the recent advent of cutting-edge chemical biology and mass spectrometry tools has greatly facilitated the process. Compared with O-GlcNAc, DNA damage response (DDR) is a relatively intensively studied area that could be traced to before the elucidation of the structure of DNA. Unexpectedly, yet somewhat expectedly, O-GlcNAc has been found to regulate various DDR pathways: homologous recombination, nonhomologous end joining, base excision repair, and translesion DNA synthesis. In this review, we first cover the recent structural studies of the O-GlcNAc transferase and O-GlcNAcase, the elegant duo that "writes" and "erases" O-GlcNAc modification. Then we delineate the intricate roles of O-GlcNAc transferase and O-GlcNAcase in DDR. We envision that this is only the beginning of our full appreciation of how O-GlcNAc regulates the blueprint of life-DNA.

Evaluation of multiscale mechanisms of ultrasound-assisted extraction from porous plant materials: Experiment and modeling on this intensified process.

Ultrasound-assisted extraction (UAE) is an intensified mass transfer process, which can utilize natural resources effectively, but still lacks detailed mechanisms for multiscale effects. This study investigates the mass transfer mechanisms of UAE combined with material's pore structure at multiscale. Porous material was prepared by roasting green coffee beans (GCB) at 120 °C (RCB120) and 180 °C (RCB180), and their UAE efficiency for phytochemicals (caffeine, trigonelline, chlorogenic acid, caffeic acid) were evaluated by experiment and modeling. Besides, the physicochemical properties, mass transfer kinetics, and multi-physical field simulation were studied. Results indicated that positive synergy effects on extraction existed between ultrasound and material's pore structure. Higher mass transfer coefficients of UAE (GCB 0.16 min-1, RCB120 0.38 min-1, RCB180 0.46 min-1) was achieved with higher total porosity (4.47 %, 9.17 %, 13.52 %) and connected porosity (0 %, 3.79 %, 5.98 %). Moreover, simulation results revealed that micro acoustic streaming and pressure difference around particles were the main driving force for enhancing mass transfer, and the velocity (0.29-0.36 m/s) increased with power density (0.64-1.01 W/mL). The microscale model proved that increased yield from UAE-RCB was attributed to internal convection diffusion within particles. This study exploited a novel benefit of ultrasound on extraction and inspired its future application in non-thermal food processing.

Establishment and application of a rapid assay for GII.4/GII.17 NoV detection based on the combination of CRISPR/Cas13a and isothermal amplification.

Introduction: Norovirus (NoV) is one of the most important agents responsible for viral acute gastroenteritis, among which GII.4 NoV is the predominant strain worldwide, and GII.17 NoV surpassed GII.4 in some epidemic seasons. Rapid and accurate gene recognition is essential for a timely response to NoV outbreaks. Methods: In the present study, the highly conserved regions of GII.4 and GII.17 NoVs were identified in the junction of open reading frame (ORF) 1 and ORF2 and then amplified by isothermal recombinase-aided amplification (RAA), followed by the cleavage of CRISPR-Cas13a with screened CRISPR RNAs (crRNAs) and RAA primers. The entire detection procedure could be completed within 40 min using a thermostat, and the results could be read out by the naked eye under a portable blue light transilluminator. Discussion: The assay showed a high sensitivity of 97.96% and a high specificity of 100.0%. It offered a low limit of detection (LOD) of 2.5×100 copies/reaction and a coincidence rate of 96.75% in 71 clinical fecal samples. Overall, rapid and inexpensive detection of GII.4/GII.17 NoVs was established, which makes it possible to be used in areas with limited resources, particularly in low-income countries. Furthermore, it will contribute to assessing transmission risks and implementing control measures for GII.4/GII.17 NoVs, making healthcare more accessible worldwide.

Comparison of the perinatal outcomes of expected high ovarian response patients and normal ovarian response patients undergoing frozen-thawed embryo transfer in natural/small amount of HMG induced ovulation cycles.

BACKGROUND: Due to the high risk of complications in fresh transfer cycles among expected high ovarian response patients, most choose frozen-thawed embryo transfer (FET). There are currently few researches on whether the FET outcomes of expected high ovarian response patients with regular menstrual cycles are similar to those of normal ovarian response. Therefore, our objective was to explore and compare pregnancy outcomes and maternal and neonatal outcomes of natural FET cycles between patients with expected high ovarian response and normal ovarian response with regular menstrual cycles based on the antral follicle count (AFC). METHODS: This retrospective cohort study included 5082 women undergoing natural or small amount of HMG induced ovulation FET cycles at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 1, 2017, to March 31, 2021. The population was divided into expected high ovarian response group and normal ovarian response group based on the AFC, and the differences in patient characteristics, clinical outcomes and perinatal outcomes between the two groups were compared. RESULTS: Regarding clinical outcomes, compared with the normal ovarian response group, patients in the expected high ovarian response group had a higher clinical pregnancy rate (57.34% vs. 48.50%) and live birth rate (48.12% vs. 38.97%). There was no difference in the early miscarriage rate or twin pregnancy rate between the groups. Multivariate logistic regression analysis suggested that the clinical pregnancy rate (adjusted OR 1.190) and live birth rate (adjusted OR 1.171) of the expected high ovarian response group were higher than those of the normal ovarian response group. In terms of maternal and infant outcomes, the incidence of very preterm delivery in the normal ovarian response group was higher than that in the expected high ovarian response group (0.86% vs. 0.16%, adjusted OR 0.131), Other maternal and infant outcomes were not significantly different. After grouping by age (< 30 y, 30-34 y, 35-39 y), there was no difference in the incidence of very preterm delivery among the age subgroups. CONCLUSION: For patients with expected high ovarian response and regular menstrual cycles undergoing natural or small amount of HMG induced ovulation FET cycles, the clinical and perinatal outcomes are reassuring. For patients undergoing natural or small amount of HMG induced ovulation FET cycles, as age increases, perinatal care should be strengthened during pregnancy to reduce the incidence of very preterm delivery.

Evolutionary origin of germline pathogenic variants in human DNA mismatch repair genes.

BACKGROUND: Mismatch repair (MMR) system is evolutionarily conserved for genome stability maintenance. Germline pathogenic variants (PVs) in MMR genes that lead to MMR functional deficiency are associated with high cancer risk. Knowing the evolutionary origin of germline PVs in human MMR genes will facilitate understanding the biological base of MMR deficiency in cancer. However, systematic knowledge is lacking to address the issue. In this study, we performed a comprehensive analysis to know the evolutionary origin of human MMR PVs. METHODS: We retrieved MMR gene variants from the ClinVar database. The genomes of 100 vertebrates were collected from the UCSC genome browser and ancient human sequencing data were obtained through comprehensive data mining. Cross-species conservation analysis was performed based on the phylogenetic relationship among 100 vertebrates. Rescaled ancient sequencing data were used to perform variant calling for archeological analysis. RESULTS: Using the phylogenetic approach, we traced the 3369 MMR PVs identified in modern humans in 99 non-human vertebrate genomes but found no evidence for cross-species conservation as the source for human MMR PVs. Using the archeological approach, we searched the human MMR PVs in over 5000 ancient human genomes dated from 45,045 to 100 years before present and identified a group of MMR PVs shared between modern and ancient humans mostly within 10,000 years with similar quantitative patterns. CONCLUSION: Our study reveals that MMR PVs in modern humans were arisen within the recent human evolutionary history.

The association between chronotype profile and temporomandibular disorders among college students.

BACKGROUND: Temporomandibular joint disorders (TMDs) are common in young adults, and the link between chronotype profile and TMDs is unclear. OBJECTIVE: This study examined TMD prevalence and chronotype distribution and explored the relationship between chronotype and TMDs in young adults. MATERIALS AND METHODS: A total of 663 students from Sichuan University completed questionnaires. Chronotype profiles were assessed using the Morningness-Eveningness Questionnaire, and TMDs were screened using the Fonseca Memory Index. To validate the findings, 68 TMD patients and 136 controls were enrolled. RESULTS: The prevalence of TMDs was 69.7%, with significant differences among chronotype profiles. The intermediate profile was the most common chronotype. Eveningness profile was associated with higher TMDs prevalence and severity. Muscle pain and side movement difficulty scores were higher in eveningness and intermediate profiles. Female gender (OR 2.345; 95% CI 1.668-3.297) was a TMD risk factor, while morningness profile (OR 0.537; 95% CI 0.297-0.970) was protective. Validation with TMD patients and controls supported these findings, showing higher eveningness profile prevalence in the TMD groups. CONCLUSIONS: TMDs have a high prevalence in college students, chronotype profiles shown to be associated with TMDs. Morningness is the protection factor in TMDs and PT, eveningness is a risk factor for IT.

Copper(I)-Catalyzed Asymmetric Allylation of Ketones with 2-Aza-1,4-Dienes.

Catalytic asymmetric allylation of ketones under proton-transfer conditions is a challenging issue due to the limited pronucleophiles and the electrophilic inertness of ketones. Herein, a copper(I)-catalyzed asymmetric allylation of ketones with 2-aza-1,4-dienes (N-allyl-1,1-diphenylmethanimines) is disclosed, which affords a series of functionalized homoallyl tertiary alcohols in high to excellent enantioselectivity. Interestingly, N-allyl-1,1-diphenylmethanimines work as synthetic equivalents of propanals. Upon the acidic workup, a formal asymmetric ß-addition of propanals to ketones is achieved. An investigation on KIE effect indicates that the deprotonation of N-allyl-1,1-diphenylmethanimines is the rate-determining step, which generates nucleophilic allyl copper(I) species. Finally, the synthetic utility of the present method is demonstrated by the asymmetric synthesis of (R)-boivinianin A and (R)-gossonorol.

Safety and Accuracy of Robot-Assisted Cervical Screw Placement: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to compare the accuracy and safety of robot-assisted (RA) cervical screw placement with conventional freehand (FH) technique. METHODS: Computer-based searches were conducted on various databases including PubMed, Embase, Cochrane Library, Web of Science, the China Biology Medicine, the China National Knowledge Infrastructure, and Wanfang Database. Inclusion criteria were studies reporting the use of RA techniques for cervical screw placement and providing data on safety and accuracy outcomes. Primary outcome indicators focused on the accuracy of screw placement, while secondary outcome indicators included operative time, intraoperative blood loss, length of hospital stay, complication rate, and radiation dose. Data from eligible studies were extracted and synthesized using a forest plot analysis. RESULTS: A total of 312 patients (1233 screws) from 6 studies were included, with 148 patients (47.4% with 567 screws) in the RA group. Perfect screw accuracy, as categorized by Gertzbein-Robbins grade A, was significantly superior with RA surgery compared to FH technique. RA screw implantation significantly reduced complication rates, intraoperative blood loss, length of hospitalization, and radiation dose compared to the conventional FH group. However, there was no statistically significant difference in surgery time between the RA and FH groups. CONCLUSIONS: RA surgery significantly improves the accuracy of cervical screw insertion and offers potential advantages in terms of reduced complications and blood loss, shorter hospital stays, and decreased radiation exposure. However, the impact on operative time remains uncertain. Further high-quality studies, including large-scale randomized controlled trials, are needed to strengthen the evidence base.

High-Temperature Failure Evolution Analysis of K-Type Film Thermocouples.

Ni90%Cr10% and Ni97%Si3% thin-film thermocouples (TFTCs) were fabricated on a silicon substrate using magnetron sputtering technology. Static calibration yielded a Seebeck coefficient of 23.00 µV/°C. During staged temperature elevation of the TFTCs while continuously monitoring their thermoelectric output, a rapid decline in thermoelectric potential was observed upon the hot junction reaching 600 °C; the device had failed. Through three cycles of repetitive static calibration tests ranging from room temperature to 500 °C, it was observed that the thermoelectric performance of the TFTCs deteriorated as the testing progressed. Utilizing the same methodology, Ni-Cr and Ni-Si thin films corresponding to the positive and negative electrodes of the TFTCs were prepared. Their resistivity after undergoing various temperature annealing treatments was measured. Additionally, their surfaces were characterized using Scanning Electron Microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS). The causes behind the decline in thermoelectric performance at elevated temperatures were analyzed from both chemical composition and microstructural perspectives.

Classification of PTEN missense VUS through exascale simulations.

Phosphatase and tensin homolog (PTEN), a tumor suppressor with dual phosphatase properties, is a key factor in PI3K/AKT signaling pathway. Pathogenic germline variation in PTEN can abrogate its ability to dephosphorylate, causing high cancer risk. Lack of functional evidence lets numerous PTEN variants be classified as variants of uncertain significance (VUS). Utilizing Molecular Dynamics (MD) simulations, we performed a thorough evaluation for 147 PTEN missense VUS, sorting them into 66 deleterious and 81 tolerated variants. Utilizing replica exchange molecular dynamic (REMD) simulations, we further assessed the variants situated in the catalytic core of PTEN's phosphatase domain and uncovered conformational alterations influencing the structural stability of the phosphatase domain. There was a high degree of agreement between our results and the variants classified by Variant Abundance by Massively Parallel Sequencing, saturation mutagenesis, multiplexed functional data and experimental assays. Our extensive analysis of PTEN missense VUS should benefit their clinical applications in PTEN-related cancer. SIGNIFICANCE STATEMENT: Classification of PTEN variants affecting its lipid phosphatase activity is important for understanding the roles of PTEN variation in the pathogenesis of hereditary and sporadic malignancies. Of the 3000 variants identified in PTEN, 1296 (43%) were assigned as VUS. Here, we applied MD and REMD simulations to investigate the effects of PTEN missense VUS on the structural integrity of the PTEN phosphatase domain consisting the WPD, P and TI active sites. We classified a total of 147 missense VUS into 66 deleterious and 81 tolerated variants by referring to the control group comprising 54 pathogenic and 12 benign variants. The classification was largely in concordance with these classified by experimental approaches.

Analysis of cumulative live birth rate outcomes of three ovarian stimulation protocols in patients after laparoscopic cystectomy of ovarial endometrioma: a retrospective cohort study.

BACKGROUND: Previous studies have reported that after laparoscopic cystectomy of ovarial endometrioma, the ovarian response to gonadotropin (Gn) significantly decreased. However, for patients with diminished ovarian reserve (DOR) after ovarian surgery, how to choose the most appropriate controlled ovarian hyperstimulation protocol has not been concluded. Compared with the traditional agonist regimen, the gonadotropin (Gn)-releasing hormone (GnRH) antagonist, microstimulation, and progestin-primed ovarian stimulation (PPOS) protocols are simple to operate and have a shorter cycle, which are often used in patients with DOR. So the purpose of our study is to compare the assisted reproductive outcomes of these three controlled ovarian hyperstimulation protocols in patients with DOR following laparoscopic cystectomy of ovarial endometrioma. METHODS: In this retrospective cohort study, 89 patients with DOR who had undergone in vitro fertilisation/intracytoplasmic sperm injection at the Department of Reproductive Medicine at the Third Affiliated Hospital of Zhengzhou University from 1 to 2018 to 31 December 2020 were included. According to the controlled ovarian hyperstimulation protocols employed, the patients were divided into GnRH antagonist (38 patients), PPOS (27 patients), and microstimulation (24 patients) groups. The basic data and clinical outcomes of the three groups were compared. The main outcome measure was the cumulative live birth rate. RESULTS: No significant differences in the age of the female patients and their spouses and female patients' body mass index and basal endocrine levels (follicle-stimulating hormone and oestradiol) were noted among the three groups (P > 0.05). The GnRH antagonist group had higher antral follicle counts, greater endometrial thickness on the human chorionic Gn injection day, greater number of oocytes retrieved, and higher two pronuclear embryo counts than did the other two groups. However, the starting dosage of Gn was lower in the GnRH antagonist group than in the other two groups. The microstimulation group had a significantly higher oocyte output rate and high-quality embryo rate than did the other two groups (P < 0.05). No significant differences in the total dosage of Gn, cumulative pregnancy rate, cumulative live birth rate, viable embryo rate, and blastocyst formation rate were observed among the three groups (P > 0.05). CONCLUSION: In conclusion, for patients aged under 40 years who experienced DOR after laparoscopic cystectomy of ovarial endometrioma, GnRH antagonist protocol and PPOS protocol can obtain better ovulation induction outcomes and cumulative live birth rate than microstimulation protocol, and are more suitable ovulation induction protocols.

Development and evaluation of a new luciferase immunosorbent assay to detect GII.6 norovirus-specific IgG in different domestic and wild animals.

Noroviruses (NoVs) are the leading viral pathogens globally causing acute gastroenteritis (AGE) in humans, posing a significant global health threat and economic burden. Recent investigations revealed that human NoVs had been detected in different animals, which raises concerns about whether NoVs are potential zoonotic diseases. This study developed a novel luciferase immunosorbent assay (LISA) to detect GII.6 NoV IgG based on P protein of VP1. The LISA showed high specificity (99.20%) and sensitivity (92.00%) with 4-16 times more sensitivity compared with an ELISA. NoV-LISA was reproducible with human serum regarding the inter- and intra-assay coefficient of variance values. Potential cross-reactivity was also evaluated using mice serum immunized by other antigens, which showed that NoV-LISA could differentiate GII.6 NoV from rotavirus and various genotypes of NoV. Specific GII.6 NoV IgG was widely detected in different domestic and wild animals, including dogs, pigs, bats, rats, and home shrews, with various IgG-positive rates ranging from 2.5 to 74.4%. In conclusion, our newly developed NoV-LISA assay is suitable for NoV-specific IgG detection in humans and animals. The wide distribution of IgG antibodies against human NoV indicates potential zoonotic transmission between humans and animals.