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Background: Gender-affirming bilateral orchiectomy (GABO) may be completed as either a standalone procedure (sGABO) or at the same time as gender-affirming vaginoplasty (vGABO). GABO is postulated to decrease gender-affirming hormone therapy (GAHT) dosages and reduce gender dysphoria, but these phenomena are not empirically described in the medical literature., Aim: The primary aim of this study was to describe changes in GAHT dosages after sGABO and vGABO. A secondary aim was to assess sGABO patients' preoperative decision-making priorities and postoperative satisfaction., Methods: A retrospective chart review identified 204 patients who completed GABO as either a standalone procedure (64% of patients) or at the same time as vaginoplasty (36%). Patient demographic data, surgical outcomes, and pre- and postoperative GAHT dosage data were recorded. Patients completed an opinion questionnaire to assessed decision-making priorities, as well as postoperative satisfaction and changes in quality-of-life measures., Outcomes: Primary outcomes included pre- and postoperative dosages of estradiol, progesterone, and spironolactone. Secondary outcomes included sGABO patient priorities, satisfaction with sGABO, changes in quality-of-life measures between sGABO and vGABO patients, and sGABO recommendations to future patients., Results: The sGABO and vGABO patients experienced a statistically significant dosage reduction in all three GAHT assessed: estradiol, progesterone, and spironolactone ( P  < .05). All patients discontinued spironolactone postoperatively. Zero complications related to GABO were recorded for patients in either group. The patient questionnaire revealed that sGABO patients prioritize decreasing endogenous testosterone and reducing their GAHT as most important in their decision to undergo sGABO prior to vaginoplasty. A majority of sGABO patients reported improvement in all nine quality-of-life indices. None of the sGABO patients would recommend against sGABO to a friend who is waiting for vaginoplasty., Clinical Implications: For patients who are interested in vaginoplasty, sGABO may serve as a more immediate, low-risk, intermediary step that comes with the benefits of GABO, including significant GAHT medication reduction and gender dysphoria relief., Strengths and Limitations: This study offers a comprehensive evaluation of the impact of GABO on patients, combining empirical data with subjective patient feedback. Limitations include the retrospective design and the use of unvalidated survey questions., Conclusion: Prevaginoplasty GABO is a viable option to more immediately alleviate gender dysphoria and reduce GAHT medications for patients who are interested in gender-affirming vaginoplasty., Competing Interests: Author M.M.G. is the principal investigator for NIH R01 clinical study #1R01CA201709-01; owner/coinventor of MLM Sante, LLC; cofounder of Safe Medical Designs, LLC; and lecture honoraria for WPATH's Global Education Initiative Foundation., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Copy number variations (CNVs) play pivotal roles in disease susceptibility and have been intensively investigated in human disease studies. Long-read sequencing technologies offer opportunities for comprehensive structural variation (SV) detection, and numerous methodologies have been developed recently. Consequently, there is a pressing need to assess these methods and aid researchers in selecting appropriate techniques for CNV detection using long-read sequencing. Hence, we conducted an evaluation of eight CNV calling methods across 22 datasets from nine publicly available samples and 15 simulated datasets, covering multiple sequencing platforms. The overall performance of CNV callers varied substantially and was influenced by the input dataset type, sequencing depth, and CNV type, among others. Specifically, the PacBio CCS sequencing platform outperformed PacBio CLR and Nanopore platforms regarding CNV detection recall rates. A sequencing depth of 10x demonstrated the capability to identify 85% of the CNVs detected in a 50x dataset. Moreover, deletions were more generally detectable than duplications. Among the eight benchmarked methods, cuteSV, Delly, pbsv, and Sniffles2 demonstrated superior accuracy, while SVIM exhibited high recall rates., (© The Author(s) 2024. Published by Oxford University Press.)

The recent discovery of public antibodies targeting Plasmodium falciparum -encoded repetitive interspersed families of polypeptides (RIFINs), which contain extracellular immunoglobulin-like domains from LAIR1 or LILRB1, constitutes a significant step forward in comprehending the reactivity of the Plasmodium parasite. These antibodies arise from unique B cell clones and demonstrate extensive cross-reactivity through their interaction with P. falciparum RIFINs. LAIR1 and LILRBs are specialized type I transmembrane glycoproteins, classified as immune inhibitory receptors, restricted to primates and mainly found on hematopoietic cells. They are instrumental in modulating interactions within the tumor microenvironment and across the immune system, and are increasingly recognized as important in anti-cancer immunotherapy and pathogen defense. The presence of LAIR1/LILRB1-containing antibodies offers new insights into malaria parasite evasion strategies and the immune system's response. Additionally, the innovative method of integrating extra exons into the antibody switch region is a noteworthy advancement, enriching the strategies for the generation of a varied array of bispecific and multispecific antibodies., Competing Interests: C.Z. has patents licensed to, holds equity in, and has Sponsored Research Agreements with Immune-Onc Therapeutics. All the other authors declare that they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Antibody Therapeutics.)

Large-scale genome-wide association studies (GWAS) have provided profound insights into complex traits and diseases. Yet, deciphering the fine-scale molecular mechanisms of how genetic variants manifest to cause the phenotypes remains a daunting task. Here, we present COLOCdb (https://ngdc.cncb.ac.cn/colocdb), a comprehensive genetic colocalization database by integrating more than 3000 GWAS summary statistics and 13 types of xQTL to date. By employing two representative approaches for the colocalization analysis, COLOCdb deposits results from three key components: (i) GWAS-xQTL, pair-wise colocalization between GWAS loci and different types of xQTL, (ii) GWAS-GWAS, pair-wise colocalization between the trait-associated genetic loci from GWASs and (iii) xQTL-xQTL, pair-wise colocalization between the genetic loci associated with molecular phenotypes in xQTLs. These results together represent the most comprehensive colocalization analysis, which also greatly expands the list of shared variants with genetic pleiotropy. We expect that COLOCdb can serve as a unique and useful resource in advancing the discovery of new biological mechanisms and benefit future functional studies., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Leveraging genetics insights to promote drug repurposing has become a promising and active strategy in pharmacology. Indeed, among the 50 drugs approved by FDA in 2021, two-thirds have genetically supported evidence. In this regard, the increasing amount of widely available genome-wide association studies (GWAS) datasets have provided substantial opportunities for drug repurposing based on genetics discoveries. Here, we developed PharmGWAS, a comprehensive knowledgebase designed to identify candidate drugs through the integration of GWAS data. PharmGWAS focuses on novel connections between diseases and small-molecule compounds derived using a reverse relationship between the genetically-regulated expression signature and the drug-induced signature. Specifically, we collected and processed 1929 GWAS datasets across a diverse spectrum of diseases and 724 485 perturbation signatures pertaining to a substantial 33609 molecular compounds. To obtain reliable and robust predictions for the reverse connections, we implemented six distinct connectivity methods. In the current version, PharmGWAS deposits a total of 740 227 genetically-informed disease-drug pairs derived from drug-perturbation signatures, presenting a valuable and comprehensive catalog. Further equipped with its user-friendly web design, PharmGWAS is expected to greatly aid the discovery of novel drugs, the exploration of drug combination therapies and the identification of drug resistance or side effects. PharmGWAS is available at https://ngdc.cncb.ac.cn/pharmgwas., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background and Aims: Early diagnosis of aortic stenosis (AS) is critical to prevent morbidity and mortality but requires skilled examination with Doppler imaging. This study reports the development and validation of a novel deep learning model that relies on two-dimensional (2D) parasternal long axis videos from transthoracic echocardiography without Doppler imaging to identify severe AS, suitable for point-of-care ultrasonography., Methods and Results: In a training set of 5257 studies (17 570 videos) from 2016 to 2020 [Yale-New Haven Hospital (YNHH), Connecticut], an ensemble of three-dimensional convolutional neural networks was developed to detect severe AS, leveraging self-supervised contrastive pretraining for label-efficient model development. This deep learning model was validated in a temporally distinct set of 2040 consecutive studies from 2021 from YNHH as well as two geographically distinct cohorts of 4226 and 3072 studies, from California and other hospitals in New England, respectively. The deep learning model achieved an area under the receiver operating characteristic curve (AUROC) of 0.978 (95% CI: 0.966, 0.988) for detecting severe AS in the temporally distinct test set, maintaining its diagnostic performance in geographically distinct cohorts [0.952 AUROC (95% CI: 0.941, 0.963) in California and 0.942 AUROC (95% CI: 0.909, 0.966) in New England]. The model was interpretable with saliency maps identifying the aortic valve, mitral annulus, and left atrium as the predictive regions. Among non-severe AS cases, predicted probabilities were associated with worse quantitative metrics of AS suggesting an association with various stages of AS severity., Conclusion: This study developed and externally validated an automated approach for severe AS detection using single-view 2D echocardiography, with potential utility for point-of-care screening., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The effects of male circumcision on sexual function remain controversial. Heterogeneity across previous studies and low-quality scientific evidence have resulted in poor understanding of the effects of circumcision on erogenous sensation of the penis and orgasm function., Aim: In this study we sought to describe and assess differences in erogenous genital sensation and reported orgasm function in circumcised compared with uncircumcised men., Methods: Adult male subjects who were recruited on a paid anonymous online survey platform were shown illustrations of 12 anatomic regions of the penis. Subjects were prompted to designate regions as pleasurable when touched during partnered sex and to rate each on a 1-10 scale, with higher erogeneity scores correlating with greater pleasure. Subjects were also asked to characterize their orgasms across 6 experiential domains., Outcomes: Outcomes were differences between circumcised and uncircumcised men in the probabilities that regions would be designated as pleasurable, average pleasure scores, and self-reported orgasm parameters., Results: In total, 227 circumcised (mean [SD] age 46.6 [17.7] years) and 175 uncircumcised men (47.8 [18.1] years) completed the survey. There were no significant differences in average ratings across all regions between circumcised and uncircumcised men. However, significantly more circumcised men reported preferences for the tip of the penis (38% vs 17%, P = .02) and the middle third of the ventral penile shaft (63% vs 48%, P = .04). Additionally, there were no significant differences in orgasm quality and function across all queried domains between circumcised and uncircumcised cohorts., Clinical Implications: Our findings suggest that circumcision does not change how men describe erogenous genital sensation or how they experience orgasm., Strengths and Limitations: In this study we expanded upon existing literature regarding comparison of sexual function in circumcised and uncircumcised men in its scale and investigation of diverse domains. Limitations include the survey format of data collection., Conclusion: We found no differences in reported erogenous ratings or orgasm function between circumcised and uncircumcised men. These findings suggest that male circumcision does not negatively impact penile erogeneity or orgasm function., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A broad range of complex phenotypes are related to dysfunctions in brain (hereafter referred to as brain-related traits), including various mental and behavioral disorders and diseases of the nervous system. These traits in general share overlapping symptoms, pathogenesis, and genetic components. Here, we present Brain Catalog (https://ngdc.cncb.ac.cn/braincatalog), a comprehensive database aiming to delineate the genetic components of more than 500 GWAS summary statistics datasets for brain-related traits from multiple aspects. First, Brain Catalog provides results of candidate causal variants, causal genes, and functional tissues and cell types for each trait identified by multiple methods using comprehensive annotation datasets (58 QTL datasets spanning 6 types of QTLs). Second, Brain Catalog estimates the SNP-based heritability, the partitioning heritability based on functional annotations, and genetic correlations among traits. Finally, through bidirectional Mendelian randomization analyses, Brain Catalog presents inference of risk factors that are likely causal to each trait. In conclusion, Brain Catalog presents a one-stop shop for the genetic components of brain-related traits, potentially serving as a valuable resource for worldwide researchers to advance the understanding of how GWAS signals may contribute to the biological etiology of brain-related traits., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: No nomogram exists to predict maximum achievable neovaginal depth before penile inversion vaginoplasty (PIV) based on available penile & scrotal skin (SS). Maximal depth is important to patients and is determined by available skin and available anatomic space within the pelvis and varies with surgical technique., Aim: We endeavored to create a nomogram to predict expected postoperative vaginal depth., Methods: Retrospective review of all patients undergoing primary PIV at a single institution from June 2017 to February 2020 (n = 60). Pre-op: Dorsal penile and midline scrotal skin length were measured. Intra-op: Tubularized scrotal skin length measured on a dilator. Immediate post-op: Final vaginal depth measured with a dilator., Outcomes: The amount of available penile and scrotal skin was not associated with vaginal depth. The only variable that did significantly increase depth was the use of penile + scrotal skin, as compared to penile skin alone. (P < .001) RESULTS: In patients who underwent PIV-SS, the final vaginal depth (13.3 ± 1.9 cm) was 87% of pre-op measured penile skin length (15.3 ±- 3.0 cm). In patients who underwent PIV+SS, pre-op penile skin length was 11.1 ± 4.7±cm and pre-op midline scrotal length was 22.8 ± 2.6 cm. with a final post-op vaginal canal depth of 15.2 ± 1.3 cm. In 45/46 (98%) surgeries utilizing SS grafts, SS tube length exceeded the length necessary to achieve maximal vaginal depth, and required trimming and discard. Given that in most cases there was an excess of SS, final post-op depth equaled the maximal vaginal depth that could be surgically dissected, and was not limited by the amount of available skin., Clinical Implications: Our findings suggest that for most patients it should not be necessary to include additional tissue sources (eg, peritoneum) to create a vaginal canal during primary vaginoplasty., Strengths and Limitations: Any penile skin that was discarded due to poor quality (eg, tight phimosis, poor viability) was not measured and accounted for. This likely resulted in a slight overestimation of the contribution of the penile skin to the final vaginal depth, but did not change the overall finding that final depth was not limited by available skin., Conclusion: SS grafts, when harvested and tubularized using optimized technique, supplied an excess of skin necessary to line a vaginal canal space of maximal achievable depth. We found that additional tissue sources can, instead, be reserved for future salvage surgery if it becomes necessary to augment depth. Smith SM, Yuan N, Stelmar J, et al. Penile and Scrotal Skin Measurements to Predict Final Vaginal Depth With Penile Inversion Vaginoplasty. Sex Med 2022;10:100569., Competing Interests: Disclosures None., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Gender-affirming peritoneal vaginoplasty has been described, and previous descriptions are modifications of the Davydov technique., Aim: To describe our alternative technique for gender-affirming peritoneal vaginoplasty (PV) using a single-pedicled, urachus-peritoneal hinge flap, discussing proposed advantages., Methods: Retrospective review of all consecutive transfeminine patients with neovaginal shortening after prior penile inversion vaginoplasty (PIV) who underwent our PV technique from May 2019 to July 2022.  PV was performed via combined transperineal and laparoscopic (robot-assisted) approaches. After spatulation of the neovaginal remnant, a midline, inferiorly based urachus-peritoneal hinge flap was elevated craniocaudally from the umbilicus to the mid-posterior bladder. The free end of the flap was flipped posteriorly and sutured to posterior edge of the open canal remnant, forming a peritoneal pouch. The lateral edges of the pouch were sutured together for water-tight closure. Patients resumed dilation on POD 6 and douching on POD 10., Main Outcome Measures: Ten transfeminine patients underwent PV, with good outcomes. We measured: Pre-op penile and scrotal skin lengths, intra-op tubularized scrotal skin length, pre and post-op vaginal depth and width (immediate and at last follow-up)., Results: Pre-op: mean neovaginal depth was 9.2cm (SD 1.5); width was 12cm. Immediate post-op: mean depth was 15.1 cm (SD 2.2 cm, mean net increase: 5.9 cm). At mean follow-up of 18.3 months, mean depth was 12.5 cm (SD 2.1 cm, mean net increase: 3.3 cm) and width was 12 cm. There were no immediate post-op complications. Eight (80%) of the 10 patients report satisfactory vaginal receptive intercourse. The other 2 have not yet attempted vaginal receptive intercourse., Clinical Implications: Advantages of the proposed technique over existing techniques include no tension on peritoneal suture lines and total exclusion of the rectum., Strengths and Limitations: Strengths include a short learning curve for urologic surgeons with robotic experience.  The study is limited by small sample size., Conclusions: Our PV technique is a safe and effective option for salvage peritoneal vaginoplasty after primary PIV. Smith SM, Yuan N, Stelmar J, et al. An Alternative Option for Gender-Affirming Revision Vaginoplasty: The Tubularized Urachus-Peritoneal Hinge Flap. Sex Med 2022;10:100572., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Permanent genital hair removal is required before gender-affirming vaginoplasty to prevent hair-related complications. No previous studies have directly compared the relative efficacy, costs, and patient experiences with laser hair removal (LHR) vs electrolysis treatments. Food and Drug Administration (FDA) oversight of medical devices is poorly understood and commonly misrepresented, adversely affecting patient care., Aim: This study compares treatment outcomes of electrolysis and LHR for genital hair removal and investigates FDA regulation of electrolysis and LHR devices., Methods: Penile-inversion vaginoplasty and shallow-depth vaginoplasty patients completed surveys about their preoperative hair removal, including procedure type, number/frequency of sessions, cost, and discomfort. Publicly available FDA-review documents and databases were reviewed., Main Outcomes Measure: Compared to electrolysis, LHR was associated with greater efficiency, decreased cost, decreased pain, and improved patient satisfaction., Results: Of 52 total (44 full-depth and 8 shallow-depth) vaginoplasty patients, 22 of 52 underwent electrolysis only, 15 of 52 underwent laser only, and 15 of 52 used both techniques. Compared to patients that underwent LHR only, patients that underwent only electrolysis required a significantly greater number of treatment sessions (mean 24.3 electrolysis vs 8.1 LHR sessions, P < .01) and more frequent sessions (every 2.4 weeks for electrolysis vs 5.3 weeks for LHR, P < .01) to complete treatment (defined as absence of re-growth over 2 months). Electrolysis sessions were significantly longer than LHR sessions (152 minutes vs 26 minutes, P < .01). Total treatment costs for electrolysis ($5,161) were significantly greater than for laser ($981, P < .01). Electrolysis was associated with greater pain and significantly increased need for pretreatment analgesia, which further contributed to higher net costs for treatment with electrolysis vs laser. Many LHR and electrolysis devices have been FDA-cleared for safety, but the FDA does not assess or compare clinical efficacy or efficiency., Clinical Implications: For patients with dark-pigmented hair, providers should consider LHR as the first-line treatment option for preoperative hair removal before gender-affirming vaginoplasty., Strength and Limitations: This is the first study to compare electrolysis and LHR for genital hair removal. The discussion addresses FDA review/oversight of devices, which is commonly misrepresented. Limitations include the survey format for data collection., Conclusion: When compared with electrolysis, LHR showed greater treatment efficiency (shorter and fewer treatment sessions to complete treatment), less pain, greater tolerability, and lower total cost. Our data suggests that, for patients with dark genital hair, providers should consider recommending laser as the first-line treatment for permanent genital hair removal before vaginoplasty. Yuan N, Feldman A, Chin P, et al. Comparison of Permanent Hair Removal Procedures before Gender-Affirming Vaginoplasty: Why We Should Consider Laser Hair Removal as a First-Line Treatment for Patients Who Meet Criteria. Sex Med 2022;10:100545., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Most complications after masculinizing genital gender-affirming surgery (gGAS) are associated with urethral lengthening (+UL). While many transmasculine patients desire +UL for standing urination, not all patients prioritize this benefit over the significantly increased risk of complications. Currently, phalloplasty without UL (-UL) appears to be seldom offered, and previous -UL techniques create genital anatomy that is visibly different from the anatomy created by phallourethroplasty+UL (P+UL)., Aim: To describe a novel surgical technique to create a normal-appearing phallus tip, scrotum, and perineal urethral opening that avoids urethral complications associated with +UL., Methods: We describe our surgical technique and approach to patient counseling. We report patient satisfaction outcomes from the first cohort of patients to undergo this 'modified phallourethroplasty' (-UL) approach to date., Outcomes: Among patients who elected phalloplasty over metoidioplasty, 13/40 (32.5%) patients elected P-UL. Prior to 1/2020, before we standardized how we presented this option to patients, 17.4% elected this option. Of the patients that elected P-UL, 8 have completed first-stage and 7 have completed second-stage surgeries., Results: All patients that have undergone P-UL have expressed satisfaction with body image and urinary function. Among patients asked to rank which of 14 preoperative factors were most important (1 = most important, 14 = least important), having a normal-appearing phallus (mean rank 4.14) and minimizing complications (mean rank 8.14) were ranked more highly than ability to urinate in a standing position (mean rank 9.14). When asked what factors most influenced their choice to have -UL (ranked from 1 to 9), elimination of risks was rated the most important (mean rank 2.71) and expected decrease in risk of needing revision surgery was rated the second most important (mean rank 3.57)., Clinical Implications: The significant reduction in +UL-related complications decrease morbidity, urgent revision surgeries, and cost to our healthcare system., Strengths and Limitations: Strengths include a novel technique that provides a surgical alternative to P+UL that eliminates the majority of phalloplasty related postoperative complications. Limitations include the small number of patients who have completed first and second stage surgery, and short follow up time., Conclusion: It is important to understand what factors drive individual patients' choices. Patients considering masculinizing gGAS should be offered both +UL and -UL options. The costs and benefits of each option should be presented objectively and in the context of each patient's unique priorities and needs. Smith SM, Yuan N, Lee G, et al. 'Modified Phallourethroplasty' as a Surgical Alternative to Phalloplasty With Urethral Lengthening: Technique, How We Present This Option to Patients, and Clinical Outcomes. Sex Med 2022;10:100495., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The age at which transgender women (TW) and men (TM) first experience gender dysphoria (GD) has not been reported in a U.S. population of adults seeking genital gender-affirming surgery (gGAS). Because gender is an innate part of identity, we hypothesized that untreated GD would be a part of individuals' earliest memories. Understanding GD onset can help guide providers with when and how to focus care to patients not yet identified as "transgender AIM: (i) Determine the age at which transgender adults seeking gGAS first experience GD (ii) Determine the number of life-years that transgender adults spend living with untreated GD METHODS: During initial consultation for gGAS, we asked patients the earliest age at which they experienced GD and the age at which they had their earliest episodic memory. We also queried history of anxiety, depression, and suicide attempt., Main Outcome Measures: Patients self-reported their earliest recollections of experiencing GD, earliest memories in general, and history of anxiety, depression, and suicide attempt., Results: Data from 155 TW (mean age 41.3; SD 16.3) and 55 TM (mean age 35.4; SD 10.8) were collected. Most patients (TM: 78%; TW: 73%) reported experiencing GD for the first time between ages 3 and 7 years.  For TM the mean age of onset was 6.17 years; for TW it was 6.71 years. A total of 81% of TW and 80% of TM described their first recollection of GD as one of their earliest memories. Mean years of persistent GD before the start of gender transition were 22.9 (TM) and 27.1 (TW). Rates of depression, anxiety, and suicide ideation decreased following gender transition., Conclusion: Our findings suggest that GD typically manifests in early childhood and persists untreated for many years before individuals commence gender transition. Diagnosis and early management during childhood and adolescence can improve quality of life and survival. Zaliznyak M, Yuan N, Bresee C, et al. How Early in Life do Transgender Adults Begin to Experience Gender Dysphoria? Why This Matters for Patients, Providers, and for Our Healthcare System. Sex Med 2021;9:100448., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of the Study: The aim of our study was to investigate potential adverse reactions in healthcare professionals working in Level 3 barrier protection personal protective equipment (L3PPE) to treat patients with COVID-19., Study Design: By using a convenience sampling approach, 129 out of 205 randomly selected healthcare professionals from the First Affiliated Hospital of Zhejiang University School of Medicine were invited to take part in a WeChat messaging app survey, Questionnaire Star, via a survey link. Healthcare personnel details were collected, including profession, years of professional experience and adverse reactions while wearing L3PPE. Survey results were divided by profession and years of professional experience; differences in adverse reactions were compared., Results: Among the 129 healthcare professionals surveyed, 21 (16.28%) were doctors and 108 (83.72%) were nurses. A total of 122 (94.57%) healthcare professionals experienced discomfort while wearing L3PPE to treat patients with COVID-19. The main reasons for adverse reactions and discomfort include varying degrees of adverse skin reactions, respiratory difficulties, heat stress, dizziness and nausea. Doctors had a lower incidence of rashes (χ 2 =4.519, p=0.034) and dizziness (χ 2 =4.123, p=0.042) when compared with nurses. Junior (8.5 years of experience or fewer) healthcare personnel also experienced a higher rate of heat stress when compared with senior personnel (more than 8.5 years greater) (χ 2 =5.228, p=0.022)., Conclusion: More attention should be offered to healthcare personnel wearing L3PPE to treat patients with COVID-19 because they are susceptible to developing adverse reactions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

MicroRNA396 (miR396) has been demonstrated to regulate flower development by targeting growth-regulating factors (GRFs) in annual species. However, its role in perennial grasses and its potential involvement in flowering time control remain unexplored. Here we report that overexpression of miR396 in a perennial species, creeping bentgrass (Agrostis stolonifera L.), alters flower development. Most significantly, transgenic (TG) plants bypass the vernalization requirement for flowering. Gene expression analysis reveals that miR396 is induced by long-day (LD) photoperiod and vernalization. Further study identifies VRN1, VRN2, and VRN3 homologs whose expression patterns in wild-type (WT) plants are similar to those observed in wheat and barley during transition from short-day (SD) to LD, and SD to cold conditions. However, compared to WT controls, TG plants overexpressing miR396 exhibit significantly enhanced VRN1 and VRN3 expression, but repressed VRN2 expression under SD to LD conditions without vernalization, which might be associated with modified expression of methyltransferase genes. Collectively, our results unveil a potentially novel mechanism by which miR396 suppresses the vernalization requirement for flowering which might be related to the epigenetic regulation of VRN genes and provide important new insight into critical roles of a miRNA in regulating vernalization-mediated transition from vegetative to reproductive growth in monocots.

The purpose of our article was to probe the influence of GRINA on rectal cancer and how GRINA is regulated in rectal cancer. Based on the public data, we found that GRINA was highly expressed in rectal cancer tissues and related to worse prognosis in rectal cancer patients. MiR-296 was predicted as an upstream regulatory miRNA of GRINA, which was further verified by dual-luciferase reporter assay. Moreover, we revealed that up-regulation/down-regulation of GRINA facilitated/suppressed SW1463/SW837 cell proliferation, migration, and invasion. Rescue assays indicated that the facilitating impact of GRINA on SW1463 cell proliferation and motility was abolished by miR-296 over-expression whilst the suppressing influence of GRINA on SW837 cell proliferation, migration, and invasion was reversed by miR-296 depletion. These consequences indicated that GRINA, which might be regulated by miR-296, acted stimulative important impact on rectal cancer cells, insinuating that GRINA might be a novel potential target for rectal cancer therapy.

Precision medicine calls upon deeper coverage of population-based sequencing and thorough gene-content and phenotype-based analysis, which lead to a population-associated genomic variation map or database. The Chinese Genomic Variation Database (CGVD; https://bigd.big.ac.cn/cgvd/) is such a database that has combined 48.30 million (M) SNVs and 5.77 M small indels, identified from 991 Chinese individuals of the Chinese Academy of Sciences Precision Medicine Initiative Project (CASPMI) and 301 Chinese individuals of the 1000 Genomes Project (1KGP). The CASPMI project includes whole-genome sequencing data (WGS, 25-30×) from ∼1000 healthy individuals of the CASPMI cohort. To facilitate the usage of such variations for pharmacogenomics studies, star-allele frequencies of the drug-related genes in the CASPMI and 1KGP populations are calculated and provided in CGVD. As one of the important database resources in BIG Data Center, CGVD will continue to collect more genomic variations and to curate structural and functional annotations to support population-based healthcare projects and studies in China and worldwide., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: The 2018 National NLP Clinical Challenge (2018 n2c2) focused on the task of cohort selection for clinical trials, where participating systems were tasked with analyzing longitudinal patient records to determine if the patients met or did not meet any of the 13 selection criteria. This article describes our participation in this shared task., Materials and Methods: We followed a hybrid approach combining pattern-based, knowledge-intensive, and feature weighting techniques. After preprocessing the notes using publicly available natural language processing tools, we developed individual criterion-specific components that relied on collecting knowledge resources relevant for these criteria and pattern-based and weighting approaches to identify "met" and "not met" cases., Results: As part of the 2018 n2c2 challenge, 3 runs were submitted. The overall micro-averaged F1 on the training set was 0.9444. On the test set, the micro-averaged F1 for the 3 submitted runs were 0.9075, 0.9065, and 0.9056. The best run was placed second in the overall challenge and all 3 runs were statistically similar to the top-ranked system. A reimplemented system achieved the best overall F1 of 0.9111 on the test set., Discussion: We highlight the need for a focused resource-intensive effort to address the class imbalance in the cohort selection identification task., Conclusion: Our hybrid approach was able to identify all selection criteria with high F1 performance on both training and test sets. Based on our participation in the 2018 n2c2 task, we conclude that there is merit in continuing a focused criterion-specific analysis and developing appropriate knowledge resources to build a quality cohort selection system., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Electronic health records (EHRs) were expected to yield numerous benefits. However, early studies found mixed evidence of this. We sought to determine whether widespread adoption of modern EHRs in the US has improved clinical care., Methods: We studied hospitals reporting performance measures from 2008-2015 in the Centers for Medicare and Medicaid Services Hospital Compare database that also reported having an EHR in the American Hospital Association 2015 IT supplement. Using interrupted time-series analysis, we examined the association of EHR implementation, EHR vendor, and Meaningful Use status with 11 process measures and 30-day hospital readmission and mortality rates for heart failure, pneumonia, and acute myocardial infarction., Results: A total of 1246 hospitals contributed 8222 hospital-years. Compared to hospitals without EHRs, hospitals with EHRs had significant improvements over time on 5 of 11 process measures. There were no substantial differences in readmission or mortality rates. Hospitals with CPSI EHR systems performed worse on several process and outcome measures. Otherwise, we found no substantial improvements in process measures or condition-specific outcomes by duration of EHR use, EHR vendor, or a hospital's Meaningful Use Stage 1 or Stage 2 status., Conclusion: In this national study of hospitals with modern EHRs, EHR use was associated with better process of care measure performance but did not improve condition-specific readmission or mortality rates regardless of duration of EHR use, vendor choice, or Meaningful Use status. Further research is required to understand why EHRs have yet to improve standard outcome measures and how to better realize the potential benefits of EHR systems., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The conserved microRNA396 (miR396) is involved in plant growth, development, and abiotic stress response in multiple plant species through regulating its targets, Growth Regulating Factor ( GRF ) transcription factor genes. However, the role of miR396 has not yet been characterized in perennial monocot species. In addition, the molecular mechanism of miR396-mediated abiotic stress response remains unclear. To elucidate the role of miR396 in perennial monocot species, we generated transgenic creeping bentgrass ( Agrostis stolonifera ) overexpressing Osa-miR396c , a rice miRNA396 gene. Transgenic plants exhibited altered development, including less shoot and root biomass, shorter internodes, smaller leaf area, fewer leaf veins, and epidermis cells per unit area than those of WT controls. In addition, transgenics showed enhanced salt tolerance associated with improved water retention, increased chlorophyll content, cell membrane integrity, and Na + exclusion during high salinity exposure. Four potential targets of miR396 were identified in creeping bentgrass and up-regulated in response to salt stress. RNA-seq analysis indicates that miR396-mediated salt stress tolerance requires the coordination of stress-related functional proteins (antioxidant enzymes and Na + /H + antiporter) and regulatory proteins (transcription factors and protein kinases). This study establishes a miR396-associated molecular pathway to connect the upstream regulatory and downstream functional elements, and provides insight into the miRNA-mediated regulatory networks., Competing Interests: The authors declare that they have no conflict of interest.

Plant organ development to a specific size and shape is controlled by cell proliferation and cell expansion. Here, we identify a novel Myb-like Arabidopsis gene, Development Related Myb-like1 (DRMY1), which controls cell expansion in both vegetative and reproductive organs. DRMY1 is strongly expressed in developing organs and its expression is reduced by ethylene while it is induced by ABA. DRMY1 has a Myb-like DNA-binding domain, which is predominantly localized in the nucleus and does not exhibit transcriptional activation activity. The loss-of-function T-DNA insertion mutant drmy1 shows reduced organ growth and cell expansion, which is associated with changes in the cell wall matrix polysaccharides. Interestingly, overexpression of DRMY1 in Arabidopsis does not lead to enhanced organ growth. Expression of genes involved in cell wall biosynthesis/remodeling, ribosome biogenesis and in ethylene and ABA signaling pathways is changed with the deficiency of DRMY1. Our results suggest that DRMY1 plays an essential role in organ development by regulating cell expansion either directly by affecting cell wall architecture and/or cytoplasmic growth or indirectly through the ethylene and/or ABA signaling pathways., (� The Author(s) 2018. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A high-performance liquid chromatography with ultraviolet detection (HPLC-UV) is established for the simultaneous determination of p-phthalic acid, benzoic acid, 4-carboxybenzaldehyde, m-phthalic acid, o-phthalic acid, phthalide, o-toluic acid, m-toluic acid and p-toluic acid in the residue generated during the production of p-phthalic acid (PPA). On a narrow-diameter reversed-phase C18 column, gradient elution is applied with a methanol-water-ammonium acetate-acetic acid buffer (100 mmol/L, pH 4.70) as mobile phase at a flow rate of 0.2 mL/min, and detection is operated by UV absorption at a wavelength of 254 nm. Under the conditions, these nine relative compounds, including organic acids, are well separated. The detection limits (S/N = 3) are 0.05 µg/mL-0.20 µg/mL, and the correlation coefficients of standard curves are between 0.99995 and 0.99999. Relative standard deviations for analyses of real samples are below 5.3%, and recoveries of these determined compounds ranges from 90.0 to 104.9%. The method, which provides accurate and reliable results, can effectively guide the recycling and reutilization of organic acids and related substances in PPA residue., (© The Author [2012]. Published by Oxford University Press. All rights reserved.)

As the second most abundant transition metal in humans, zinc plays essential roles in normal cellular biological functions, including metabolism, signalling, proliferation, gene expression and apoptosis. We use ZnSO(4) as a stressor in this study to investigate for the first time the effects of exogenous Zn(2+) on both the cellular distribution of zinc and zinc-related proteins and the cell cycle of human lung adenocarcinoma (A549) cells. The cellular distribution of zinc and soluble proteins was determined in the whole cell as well as in the cytoplasmic and nuclear fractions. Exogenous zinc in the tested exposure range (0-100 µM) resulted in an altered cellular distribution of both zinc and the soluble proteins, together with total glutathione (GSx), the ratio of glutathione (GSH) to glutathione disulfide (GSSG) and non-protein sulphydryl (NPSH). Surprisingly, a turning point was observed in the re-distribution trend at a concentration of approximately 50 µM ZnSO(4). It is concluded that there exists a regulatory system in A549 cells that maintains the cellular zinc content stable in the presence of a certain range of extracellular zinc concentration. In addition, an MTT assay and flow cytometric analysis showed that the ZnSO(4) treatment led to a bi-phasic variation in viability and a slight fluctuation in the apoptosis of A549 cells. Our results will help to further elucidate zinc-related cell biology and biochemistry.

A psychrophilic protease-producing bacterium, HW08, was isolated from sediment of the Yellow Sea in eastern China. On the basis of 16S rDNA sequence analysis and physiological properties, the isolate was identified as Pseudomonas lundensis. The secreted protease, named Ps5, was purified from the culture supernatant as a monomer with an apparent molecular mass of 46 kDa on SDS-PAGE. As a metalloprotease (inhibited by EDTA), the enzyme showed maximum activity at 30 degrees C at pH 10.4. It had no activity loss exposed at 4 degrees C for 60 d or under repeated freezing and thawing. Broad temperature (25-40 degrees C) and pH (7.0-11.0) stability was observed in the presence of 5 mm Ca(2+). Furthermore, the enzyme was resistant to detergent additives such as non-ionic surfactants and bleaches. It showed considerable potential for industry that requires alkaline-protease.