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Objective: To evaluate trends in the incidence and serotype profile of invasive pneumococcal disease (IPD) in Australian children under 2 years of age after the introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV).Design and Setting: Analysis of incidence rates calculated using IPD surveillance data (including age, Indigenous status and serotype of the pneumococcal isolate) from 2002 to 2007 obtained from the National Notifiable Diseases Surveillance System and population estimates obtained from the Australian Bureau of Statistics.Main Outcome Measures: Trends in IPD incidence among Indigenous and non-Indigenous children between 2002 and 2007; change in the serotype profile of IPD in non-Indigenous children after the introduction of universal 7vPCV vaccination in 2005.Results: Overall incidence of IPD decreased by 74% in all children < 2 years of age between 2002 and 2007 (P < 0.001). While the incidence of IPD caused by 7vPCV serotypes decreased significantly among both Indigenous and non-Indigenous children, the incidence of non-7vPCV serotype IPD increased significantly in non-Indigenous children (from 9.7 to 15.7 per 100 000, P < 0.001). Compared with a pre-vaccination period (2002-2004), the 2007 incidence of serotype 19A IPD in non-Indigenous children increased significantly (from 2.7 to 8.6 per 100 000, P < 0.001). In 2007, 19A was the predominant serotype causing IPD (37.7%) in all children aged < 2 years.Conclusions: The overall incidence of IPD decreased from 2002 to 2007, primarily driven by a reduction in IPD caused by 7vPCV serotypes. However, this was partially offset by a significant increase in the incidence of IPD caused by non-7vPCV serotypes, particularly 19A, in non-Indigenous children. [ABSTRACT FROM AUTHOR]

Objective: The potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) has been found through a genome-wide association study to be a strong candidate for conferring susceptibility to type 2 diabetes in East Asian and European populations. Our objective was to describe the association between polymorphisms at the KCNQ1 locus with insulin resistance, beta-cell function, and other type 2 diabetes-related traits in a sample of Chinese, Malays, and Asian Indians living in Singapore.Research Design and Methods: We examined the associations between four previously reported KCNQ1 single-nucleotide polymorphisms (SNPs) with type 2 diabetes-related traits in 3,734 participants from the population-based 1998 Singapore National Health Survey cohort (2,520 Chinese, 693 Malay, and 521 Asian Indians). Insulin resistance was calculated from fasting insulin and glucose using the homeostasis model assessment method, whereas pancreatic beta-cell function was assessed using the corrected insulin response at 120 min (CIR(120)).Results: SNPs rs2237897, rs2237892, and rs2283228 were significantly associated with type 2 diabetes (odds ratio [OR] 1.48, P = 3 x 10(-4); OR 1.38, P = 0.002; OR 1.31, P = 0.012, respectively). Within the Chinese population, the risk alleles for rs2237897, rs2237892, and rs2283228 were significantly associated with higher fasting glucose levels (P = 0.014, 0.011, and 0.034, respectively) and reduced CIR(120)(P = 0.007, 0.013, and 0.014, respectively). A similar trend was observed among the Malay and Asian Indian minority groups, although this did not reach statistical significance because of limited sample sizes.Conclusions: The increased risk for type 2 diabetes associated with KCNQ1 is likely to be caused by a reduction in insulin secretion. Further studies will be useful to replicate these findings and to fully delineate the role of KCNQ1 and its related pathways in disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Optimal glycaemic control has well-established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver-related outcomes., Aims: To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver-related mortality., Methods: In a population-based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3-year lead-in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver-related mortality., Results: We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow-up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver-related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61-0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29-1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54-0.80), sex (SHR 0.68-0.69), BMI <25 or ≥25 kg/m 2 (SHR 0.63-0.75), smoking (SHR 0.61-0.72), hepatic steatosis (SHR 0.67-0.68) and aspirin/statin/metformin use (SHR 0.67-0.75). A lower risk of liver-related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61-0.80)., Conclusions: Glycaemic control is an independent risk factor for HCC and liver-related mortality, and should be incorporated into oncoprotective strategies in the general DM population., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Osteoporotic fracture is a prevalent noncommunicable disease globally, causing significant mortality, morbidity, and disability. As the population ages, the healthcare and economic burden of osteoporotic fracture is expected to increase further. Due to its multifactorial features, the development of osteoporotic fracture involves a complex interplay of multiple risk factors, including genetic, environmental, and lifestyle factors. Helicobacter pylori, which infects approximately 43% of the world's population, has been associated with increased fracture risk due to hypochlorhydria from atrophic gastritis and systemic inflammation from elevated pro-inflammatory cytokines. However, the potential impact of H. pylori infection and eradication on fracture risk remains contentious among various studies due to the study design and inadequate adjustment of confounding factors including baseline gastritis phenotype. In this review, we provided a comprehensive evaluation of the current evidence focusing on the underlying mechanisms and clinical evidence of the association between H. pylori infection and osteoporotic fracture. We also discussed the potential benefits of H. pylori eradication on fracture risk., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aims: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus., Approach and Results: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05)., Conclusions: Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261)., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Cardiac organoids differentiated from induced pluripotent stem cells are emerging as a promising platform for pre-clinical drug screening, assessing cardiotoxicity, and disease modelling. However, it is challenging to simultaneously measure mechanical contractile forces and electrophysiological signals of cardiac organoids in real-time and in-situ with the existing methods. Here, we present a biting-inspired sensory system based on a resistive skin sensor and a microelectrode array. The bite-like contact can be established with a micromanipulator to precisely position the resistive skin sensor on the top of the cardiac organoid while the 3D microneedle electrode array probes from underneath. Such reliable contact is key to achieving simultaneous electro-mechanical measurements. We demonstrate the use of our system for modelling cardiotoxicity with the anti-cancer drug doxorubicin. The electro-mechanical parameters described here elucidate the acute cardiotoxic effects induced by doxorubicin. This integrated electro-mechanical system enables a suite of new diagnostic options for assessing cardiac organoids and tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%., Methods: This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance., Results: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively., Conclusions: VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection., Trial Registration: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

Background and Aim: We aimed to investigate the effect of metabolic dysfunction-associated steatotic liver disease (MASLD) on three-dose BNT162b2 immunogenicity to the omicron variant., Methods: Adult recipients of three doses of BNT162b2 were prospectively recruited between May and December 2021. The serology of the neutralizing antibody by live virus microneutralization (vMN) to the omicron variant was measured at baseline, day 180, and day 360 after the first dose. The primary outcome was seroconversion (vMN titer ≥ 10) at day 360. Exposure of interest was MASLD, defined as hepatic steatosis (controlled attenuation parameter ≥ 248 dB/m on transient elastography) plus at least one of five cardiometabolic risk factors. Subjects with prior COVID-19 were excluded. A multivariable logistic regression model was used to derive the adjusted odds ratio of seroconversion with MASLD by adjusting for age, sex, antibiotic use, and proton pump inhibitor use., Results: One hundred forty-eight BNT162b2 recipients (male: 48 [32.4%]; median age: 51.0 years [interquartile range, IQR: 44.5-57.3]) were recruited. The median time from the first dose to the third dose was 8.5 months (IQR: 7.9-8.9). MASLD subjects had a lower seroconversion rate than non-MASLD ones (89.6% vs 99.0%; P = 0.007). MASLD was the only independent risk factor for seroconversion (adjusted odds ratio: 0.051, 95% confidence interval: 0.002-0.440). Subgroup analysis of immunogenicity at 4 months after the third dose shows significantly lower vMN titer (13.06 [IQR: 7.69-22.20] vs 33.49 [IQR: 24.05-46.53]; P = 0.004) and seroconversion rate (76.9% vs 97.4%; P = 0.016) in MASLD than non-MASLD subjects, but not within 4 months from the third dose (vMN titer: 46.87 [IQR: 33.12-66.02] vs 41.86 [IQR: 34.47-50.91], P = 0.240; seroconversion rate: 94.3% vs 100%, P = 0.131)., Conclusion: Metabolic dysfunction-associated steatotic liver disease was a risk factor for poorer immunogenicity to the omicron variant, with a more pronounced waning effect compared among three-dose BNT162b2 recipients., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2., Methods: Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis., Results: A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2-59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. Streptococcus parasanguinis (log 10 LDA score = 2.38, p = 0.003; relative abundance of 2.97 × 10 -5 vs. 0.03%, p = 0.001), Bacteroides stercoris (log 10 LDA score = 4.29, p = 0.024; relative abundance of 0.14% vs. 2.40%, p = 0.014) and Haemophilus parainfluenzae (log 10 LDA score = 2.15, p = 0.022; relative abundance of 0.01% vs. 0, p = 0.010) were enriched in low responders. Bifidobacterium pseudocatenulatum (log 10 LDA score = 2.99, p = 0.048; relative abundance of 0.09% vs. 0.36%, p = 0.049) and Clostridium leptum (log 10 LDA score = 2.38, p = 0.014; relative abundance of 1.2 × 10 -5 % vs. 0, p = 0.044) were enriched in high responders. S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log 10 LDA score = 2.63), which contributes to inflammation and antibody production. H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log 10 LDA score = 2.14)., Conclusion: Among three-dose BNT162b2 recipients, S. parasanguinis , B. stercoris and H. parainfluenzae were associated with poorer immunogenicity at one year, while B. pseudocatenulatum and C. leptum was associated with a better response.

To evaluate the impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients, focusing on CD3 + , CD4 + , CD8 + , and natural killer (NK) cells, as well as the CD4 + /CD8 + ratio. We retrospectively reviewed medical records of breast cancer patients who underwent surgery with or without neoadjuvant chemotherapy at our medical center from January 2020 to December 2022. Patients were matched 1:1 based on propensity scores. Immune cell proportions and the CD4 + /CD8 + ratio were compared on preoperative day one and postoperative days one and seven. Among matched patients, immune cell proportions and the CD4 + /CD8 + ratio did not significantly differ between those who received neoadjuvant chemotherapy and those who did not at any of the three time points. Similar results were observed in chemotherapy-sensitive patients compared to the entire group of patients who did not receive neoadjuvant chemotherapy. However, chemotherapy-insensitive patients had significantly lower proportions of CD4 + and NK cells, as well as a lower CD4 + /CD8 + ratio, at all three time points compared to patients who did not receive neoadjuvant chemotherapy. Neoadjuvant chemotherapy may impair immune function in chemotherapy-insensitive patients, but not in those who are sensitive to the treatment., (© 2024. The Author(s).)

Intraosseous pneumatocysts are benign, gas-filled cystic structures of bone, typically asymptomatic and discovered incidentally on imaging. Their precise aetiology remains unclear, with the prevailing hypothesis being that they result from air accumulation within the bone due to a vacuum phenomenon, typically linked to an adjacent joint space or intervertebral disc. We report the case of a 37-year-old man with an incidental intraosseous pneumatocyst of the scapula, which was evaluated with CT and MRI. Using thin-slice CT, we are able to detect a tiny cortical breach suggestive of a communication between the lesion and the adjacent glenohumeral joint, lending support to the aforementioned aetiological hypothesis., (Crown Copyright © 2024 Published by Elsevier Inc. on behalf of University of Washington.)

The direct co-conversion of methane and carbon dioxide into valuable chemicals has been a longstanding scientific pursuit for carbon neutrality and combating climate change. Herein, we present a photo-driven chemical process that reforms these two major greenhouse gases together to generate green methanol and CO, two high-valued industrial chemicals. Isotopic labeling and control experiments indicate an oxygen-atom-graft occurs, wherein CO 2 transfers one O into the C-H bond of CH 4 via photo-activated interfacial catalysis with AuPd nanoparticles supported on GaN. The photoexcited AuPd/GaN interface effectively orchestrates the CH 4 oxidation and the CO 2 reduction producing 13.66 mmol g -1 of CH 3 OH yield over 10 h. This design provides a solid scientific basis for the photo-driven oxygen-atom-grafting process to be further extended to visible light region., (© 2024. The Author(s).)

Objective: Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain., Design: Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up., Results: Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5-9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (P trend <0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73-0.87)., Conclusion: Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient., Competing Interests: Competing interests: C-LC received research funding from AstraZeneca, Merck KGaA and Taiho. L-YM is an advisory board member of Gilead Sciences. WKL received speaker’s fees from AbbVie, Ferring Pharmaceuticals and Janssen. MFY received research funding from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex, Roche and is an advisory board member and/or received research funding from AbbVie, Aligos therarpeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, Roche. W-KS received speaker’s fees from AstraZeneca, is an advisory board member and received speaker’s fees of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects., Methods: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome., Results: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice., Conclusions: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes., Competing Interests: Financial disclosure/conflicts of interest: V.P. received past funding from Sigvaris AG. M.P. received institutional funding from University of Melbourne (Internal Grant Schemes), Royal Women's Hospital (Internal grant scheme), and Cancer Council NSW Project Grant RG 21-06, Centre for Research Excellence in Women's Health in Reproductive Life (CREWHiRL) Seed Funding and Project Support Grant, NHMRC (APP1163202), and Royal Children's Hospital Foundation. She received past funding from FertilityIQ webinar honorarium. She has received fee registration fees as an invited speaker by the Pacific Society of Reproductive Medicine 2023 Conference and had subsidized flights and accommodations as an invited speaker for the European Society of Human Reproduction and Embryology 2022 Conference. She was also given free registration as an invited speaker for the Annual Scientific Meeting of Breast Cancer Trials 2021. D.A. has consulted for Evestra, Exeltis, Lupin, Mithra, ObsEva, and TherapeuticsMD, received industry support for research from AbbVie, Mithra, Myovant, and ObsEva, and has stock holdings in Agile Therapeutics, InnovaGyn, Inc. N.A. receives ongoing institutional funding from the National Cancer Institute. J.C. is owner of JSCarpenter, LLC which received scale licensing fees from Mapi Research Trust (2022), consulting fees from the University of Wisconsin (spring 2022), and consulting fees from Simumetrix SMX Health (spring 2022). M.C. has been paid for developing and delivering educational presentations for Alliance Chicago, received fees for an educational video and speaking engagements with Fertility IQ, wrote a White Paper on GSM for Materna (no financial reimbursement), and is a member of The Menopause Society Board of Trustees. M.D. receives current institutional funding from National Institute of Health Research. She serves as a chief investigator on POISE study (research relevant to HRT) and a chief investigator for BLUSH study (research on treatment of menopause). She received past institutional funding from Best Practice & Research Clinical Obstetrics & Gynaecology as editor of volume on menopause management published 2022. She is an elected member of the Medical Advisory Council of the British Menopause Society, is a member of the ESHRE guideline update group on Premature Ovarian Insufficiency, is a member of the British Endocrine Society working group producing clinical guidelines on estrogen treatment, and is a member of the British Gynaecological Cancer Society working group producing clinical guidelines on HRT. T.H. received past funding from Besins and Astellas. M.H. receives ongoing funding from Rightsteps and current funding from Hello Therapeutics. L.K. has lectured and/or acted in an advisory capacity for Gedeon Richter, Dr. KADE Besins and Mithra. P.M. has received compensation as a member of the scientific advisory board of Astellas, Bayer, and Johnson & Johnson; compensation from AbbVie and Pfizer for consulting; and serves as a member of the scientific advisory board and has/had equity in Alloy, Estrigenix, and MidiHealth. She has received speaking fees and travel support from Mithra. R.E.N. has ongoing relationships with Abbott, Astellas, Bayer HealthCare AG, Besins Healthcare, Exeltis, Fidia, Gedeon Richter, HRA Pharma, Merck Healthcare, Novo Nordisk, Shionogi Limited, Theramex, and Viatris. N.P. has lectured and/or acted in an advisory capacity for Abbott, Lawley, Mithra, Novo, SeCur, and Viatris. S.R. has lectured and/or acted in an advisory capacity or conducted studies for Abbott, Bayer, Gedeon Richter, Mylan, Amgen, UCB, Theramex, and Viatris. J.S. receives grant/research support from AbbVie, Inc., Bayer Healthcare LLC., Dare´ Bioscience; Ipsen, Mylan/Viatris Inc., Myovant Sciences, Sebela Pharmaceuticals Inc. He acts as a consultant is on advisory boards for Bayer HealthCare Pharmaceuticals Inc., Besins Healthcare, California Institute of Integral Studies (CIIS), Dare´ Bioscience, Femasys Inc., Khyria, Madorra Pty Ltd., Mayne Pharma, Inc., and Vella Bioscience Inc. He serves on speaker's bureaus for Astellas Pharma, Inc., Mayne Pharma, Inc., Myovant Sciences, Inc., Pfizer Inc., Pharmavite LLC., Scynexis Inc. He is a stockholder (direct purchase) of Sermonix Pharmaceuticals. P.S. has received fees for giving educational presentations, participating in advisory boards and conducting research by Besins Healthcare, Astellas, Mylan, Labatec, Exeltis, Effik, Theramex, and Gedeon-Richter. A.J.V. has received fees for presentations and participation in an advisory board from Besins and Theramex. W.W. has received institutional support with an unrestricted grant from Pfizer and sits on the advisory boards of Pfizer, Lupin, and Biosyent. She has received fees for educational presentations for Lupin, Astellas, Bayer and Pfizer, and Biosyent. She is a board member of the International Menopause Society and the President of the Canadian Menopause Society. M.H. has received funding from Madorra for a study of a device to manage GU symptoms and is a clinical expert for the NICE Menopause Guidelines. J.T.G. is a speaker for NurtureMed Pharma, Bayer Phils, Corbridge Phils, and Zuellig Pharma. P.S. has a research consultancy relationship with Chugai Pharmaceuticals. H.J. receives grant funding from the National Institutes of Health, Merck, and Pfizer and is a consultant to Bayer, Merck, and Hello Therapeutics. She receives in kind support from Sage to her institution (drug provided to support NIH-funded trial), funds from Bayer support a pilot grant program she lead within an NIH-funded Center grant. Her spouse is employed by Arsenal Biosciences and receives equity from Merck Research Labs. N.J. is on the advisory board of Vira Health, UK. All other authors report no conflicts of interest., (Copyright © 2024 by The North American Menopause Society.)

Background: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac., Methods: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors., Results: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9-56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. Eubacterium rectale (log 10 LDA score = 4.15, p = 0.001; relative abundance of 1.4% vs. 0, p = 0.002), Collinsella aerofaciens (log 10 LDA score = 3.31, p = 0.037; 0.39% vs. 0.18%, p = 0.038), and Streptococcus salivarius (log 10 LDA score = 2.79, p = 0.021; 0.05% vs. 0.02%, p = 0.022) were enriched in low responders. The aOR of high immune response with E. rectale, C. aerofaciens , and S. salivarius was 0.03 (95% CI: 9.56 × 10 -4 -0.32), 0.03 (95% CI: 4.47 × 10 -4 -0.59), and 10.19 (95% CI: 0.81-323.88), respectively. S. salivarius had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log 10 LDA score = 2.23). C. aerofaciens similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions., Conclusion: E. rectale, C. aerofaciens , and S. salivarius correlated with poorer long-term immunogenicity following three doses of CoronaVac.

Implicit biases may negatively influence healthcare providers' behaviors toward patients from historically marginalized communities, impacting providers' communication style, clinical decision-making, and delivery of quality care. Existing interventions to mitigate negative experiences of implicit biases are primarily designed to increase recognition and management of stereotypes and prejudices through provider-facing tools and resources. However, there is a gap in understanding and designing interventions from patient perspectives. We conducted seven participatory co-design workshops with 32 Black, Indigenous, People of Color (BIPOC), Lesbian, Gay, Bisexual, Transgender, Queer/Questioning (LGBTQ+), and Queer, Transgender, Black, Indigenous, People of Color (QTBIPOC) individuals to design patient-centered interventions that help them address and recover from provider implicit biases in primary care. Participants designed four types of solutions: accountability measures, real-time correction, patient enablement tools, and provider resources. These informatics interventions extend the research on implicit biases in healthcare through inclusion of valuable, firsthand patient perspectives and experiences., (©2023 AMIA - All rights reserved.)

Objectives: This study aims to describe the effectiveness of low initial alprostadil dosages to maintain a patent ductus arteriosus (PDA) in infants with ductal-dependent congenital heart disease (DDCHD). Secondary objectives were to describe any adverse drug events, describe prescribing trends, describe ductus arteriosus diameter changes, and compare the safety and efficacy of very low and low initial alprostadil dosage regimens., Methods: This retrospective observational cohort study at the British Columbia's Women's and Children's Hospital neonatal intensive care unit and pediatric intensive care unit examined neonates admitted with DDCHD who received alprostadil to maintain ductal patency. Very low-dose alprostadil (less than 0.01 mcg/kg/min) versus low-dose alprostadil (equal to or greater than 0.01 mcg/kg/min) was examined. Effectiveness was defined as survival and infants not requiring a resuscitation event (cardiac arrest, cardiogenic shock, code blue, extracorporeal life support, requirement for emergent cardiac surgery, and respiratory acidosis). Adverse drug events with a Naranjo score of 3 or more were included., Results: Alprostadil was effective for 88% of patients, with no difference between the very low-dose and low-dose groups. Of the 75 patients included, 25 received very low-dose alprostadil. Adverse drug events were common (51%) with neonates in the low-dose group experiencing more apnea and pyrexia than neonates in the very low-dose group., Conclusions: Alprostadil therapy was effective in maintaining the PDA in neonates with DDCHD with low-dosage regimens. Adverse drug events were common with both dosage regimens; however, the very low dosage appeared to have less apnea and pyrexia., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org.)

Ovarian cancer is one of the most common malignant tumours affecting the female reproductive organs. CD147 (BSG) and CD98hc (SLC3A2) are oncogenes that form the CD98hc-CD147 complex, which regulates the proliferation, metastasis, metabolism, and cell cycle of cancer cells. The roles of the CD98hc-CD147 complex in ovarian cancer remain unclear. We analysed the expression and prognostic value of CD147 and CD98hc in ovarian cancer using the TCGA and ICGC databases. The effect of CD147 and CD98hc on the tumour immune response was analysed using the TIMER database. CD98hc was more highly expressed in normal tissues than primary tumour tissues, while CD147 was more highly expressed in primary tumour tissues than normal tissues. CD98hc expression was significantly associated with neutrophil and dendritic cell levels. CD147 and CD98hc were correlated with DNA repair, the cell cycle, and DNA replication. The CD98hc-CD147 complex could serve as a target for ovarian cancer treatment.

Herein, we present a protocol for the on-demand preparation of methanol and formic acid via selective photo-oxidation of methane with H 2 O and O 2 catalyzed by GaN. The detailed photosyntheses of methanol or formic acid from CH 4 /H 2 O or CH 4 /H 2 O/O 2 are described, respectively. In addition, we provide experimental details for the accurate quantifications of the final gas/liquid products and photoexcited oxygenated radicals. Finally, we deliver the procedure for scaling up the transformation. For complete details on the use and execution of this protocol, please refer to Han et al. (2023). 1 ., Competing Interests: Declaration of interests A US Patent for this work has been applied and is pending., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Alkanes are naturally abundant chemical building blocks that contain plentiful C(sp 3 )-H bonds. While inert, the activation of C(sp 3 )-H via hydrogen atom abstraction (HAT) stages an appealing approach to generate alkyl radicals. However, prevailing shortcomings include the excessive use of oxidants and alkanes that impede scope. We herein show the use of gallium nitride (GaN) as a non-toxic, recyclable, heterogeneous photocatalyst to enable alkyl C(sp 3 )-H in conjunction with the catalytic use of simple photosensitizer, benzophenone, to promote the desired alkyl radical generation. The dual photocatalytic cycle enables cross-dehydrogenative Minisci alkylation under mild and chemical oxidant-free conditions., (© 2023. Springer Nature Limited.)

Aim: Given a lack of interventions to identify and engage individuals with early psychosis in jail and connect them to specialty care in the community upon release, we designed a Targeted Educational Campaign (TEC) for correction officers working in jails. We report on impacts of the TEC on officers' cognitive and attitudinal outcomes., Methods: Three different cohorts of officers-totaling n = 451-took part in a survey: 200 at baseline before the TEC began, 123 at 6-months into the TEC, and 128 at 12-months into the TEC. Among each cohort of officers, four constructs were measured: (1) knowledge about early psychosis; (2) self-efficacy around detecting early psychosis and referring to mental health services within the jail; (3) expectations about the benefits of detection and referral to specialty care; and (4) social distance stigma toward detainees with early psychosis., Results: While exposure to TEC elements was as-planned in the first 6-months, exposure diminished substantially at 12-months, coinciding with increasing fatigue among correction officers due to the COVID-19 pandemic as well as serious staffing shortages. Knowledge, behavioural expectations, and self-efficacy scores improved from baseline to 6-months, with greater exposure to roll-call messages driving scores. Knowledge and behavioural expectations at 12-months were associated with having received an information post card. Social distance stigma worsened across timepoints., Conclusions: An educational campaign for jail staff can enhance knowledge, self-efficacy, and behavioural expectations regarding early psychosis, though only while the campaign elements are active. Further research should investigate whether or not social distance stigma or other types of stigma increase alongside improvements., (© 2023 John Wiley & Sons Australia, Ltd.)

The decarboxylative Minisci reaction is a versatile tool for the direct C-H alkylation of heteroarenes, where stoichiometric amounts of oxidants or expensive, precious metal reagents are commonly used. Herein, we reported a photodriven decarboxylative Minisci reaction enabled by a gallium nitride-based heterogeneous photocatalyst under mild conditions. This method can be effectively applied to a broad substrate scope of acids, including primary, secondary, and tertiary carboxylic acids and N -heteroarenes effectively. The practicability and robustness of the approach are demonstrated for the functionalization of biologically active compounds., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Co-published by University of Science and Technology of China and American Chemical Society.)

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has had a significant impact on all walks of life, in particular, environmental services workers in healthcare settings had higher workload, increased stress and greater susceptibility to COVID-19 infections during the pandemic. Despite extensive literature describing the impact of the pandemic on healthcare workers such as doctors and nurses, studies on the lived experiences of environmental services workers in healthcare settings are sparse and none has been conducted in the Asian context. This qualitative study thus aimed to examine the experiences of those who worked for a year of the COVID-19 pandemic., Methods: A purposive sample of environmental services workers was recruited from a major tertiary hospital in Singapore. Semi-structured interviews were conducted in-person, lasting around 30min, and included open-ended questions pertaining to five main domains: work experiences during COVID-19, training and education needs, resource and supplies availability, communication with management and other healthcare staff, and perceived stressors and support. These domains were identified based on team discussions and literature review. The interviews were recorded and transcribed for thematic analysis, as guided by Braun and Clarke., Results: A total of 12 environmental services workers were interviewed. After the first seven interviews, no new themes emerged but an additional five interviews were done to ensure data saturation. The analysis yielded three main themes and nine subthemes, including (1) practical and health concerns, (2) coping and resilience, and (3) occupational adaptations during the pandemic. Many expressed confidence in the preventive efficacy of proper PPE, infection control practice and COVID-19 vaccination in protecting them against COVID-19 and severe illness. Having prior experience with infectious disease outbreaks and previous training in infection control and prevention appeared to be useful as well for these workers. Despite the various challenges presented by the pandemic, they could still find meaning in their everyday work by positively impacting the wellbeing of patients and other healthcare workers in the hospital., Conclusion: Besides uncovering the concerns shared by these workers, we identified helpful coping strategies, resilience factors and certain occupational adaptations, which have implications for future pandemic planning and readiness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ng, Koh, Xin, Zainal, Tan, Thumboo and Fong.)

Background: To explore the effect and mechanism of action of miR-210 on postmenopausal osteoporosis (PMPO) in ovariectomized rats in vivo., Methods: An ovariectomized (OVX) rat model was established by ovariectomy. Tail vein injection was performed to overexpress and knock down miR-210 in OVX rats, followed by the collection of blood and femoral tissues from each group of rats. And quantitative real-time polymerase chain reaction (qRT-PCR) was applied to assess the expression level of miR-210 in femoral tissues of each group. Micro computed tomography (Micro CT) was adopted to scan the microstructure of the femoral trabecula in each group to obtain relevant data like bone mineral density (BMD), bone mineral content (BMC), trabecular bone volume fraction (BV/TV), trabecular thickness (Tb.Th), bone surface-to-volume ratio (BS/BV), and trabecular separation (Tb.Sp). ELISA was used for determining the level of bone alkaline phosphatase (BALP), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OCN), and C-terminal telopeptide of type I collagen (CTX-1) in serum; and Western blot for the protein level of Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and collagen type I alpha 1 (COL1A1) in femoral tissues., Results: MiR-210 expression was significantly decreased in femoral tissues of OVX rats. Overexpression of miR-210 could obviously increase BMD, BMC, BV/TV and Tb.Th, whereas significantly decrease BS/BV and Tb.Sp in femurs of OVX rats. Moreover, miR-210 also downregulated BALP and CTX-1 level, upregulated PINP and OCN level in the serum of OVX rats promoted the expression of osteogenesis-related markers (Runx2, OPN and COL1A1) in the femur of OVX rats. Additionally, further pathway analysis revealed that high expression of miR-210 activated the vascular endothelial growth factor (VEGF)/Notch1 signaling pathway in the femur of OVX rats., Conclusion: High expression of miR-210 may improve the micromorphology of bone tissue and modulate bone formation and resorption in OVX rats by activating the VEGF/Notch1 signaling pathway, thereby alleviating osteoporosis. Consequently, miR-210 can serve as a biomarker for the diagnosis and treatment of osteoporosis in postmenopausal rats., (© 2023. The Author(s).)

People with serious mental illnesses are disproportionately involved in the criminal legal system, often for low-level, non-violent misdemeanors. This paper examines how decision-makers at different stages of the criminal legal system articulate unique visions of the "best approach" for addressing this problem of over-representation. Focus groups and in-depth interviews were conducted with 94 stakeholders from Atlanta, Chicago, New York City, and Philadelphia to understand how decision-makers from different agencies use and process specific misdemeanor charges in relation to people with serious mental illnesses. Data were analyzed using a thematic approach. The data reveal a series of tensions regarding how criminal legal system stakeholders process people with serious mental illnesses through the misdemeanor system. Three key themes emerged from analysis. The first characterizes the shared commitment across agencies to reducing system contact among people with mental illnesses. The second explores how agencies differ on how to make good on that commitment because of the distinct values and goals they bring to the table. The final theme explores the limits of current approaches to reducing system contact for people with mental illnesses. Findings are discussed in the context of literature on "loose coupling" and the focal concerns framework and demonstrate that decisions about how and when to intervene with people with mental illnesses in the criminal legal system are influenced by the varying orientations, goals, and values of stakeholder agencies. Understanding these core differences is a critical step toward value alignment in strategies to reduce system involvement among people with mental illnesses., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers., Methods: Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review., Results: A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9-54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%-13.5%), and median duration of response was 18.4 (range, 4.2-47.2+) months. ORR was 8.7% (95% CI, 2.4%-20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3-5, 14.6%)., Conclusions: Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD-L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study., (© 2023 Merck Sharp & Dohme LLC and The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: People with mental illnesses are disproportionately entangled in the criminal legal system. Historically, this involvement has resulted from minor offending, often accompanied by misdemeanor charges. In recent years, policymakers have worked to reduce the footprint of the criminal legal system. This paper seeks to better understand how misdemeanor systems intervene in the lives of people with mental illnesses., Methods: System mapping exercises were conducted with misdemeanor system stakeholders from the jurisdictions of Atlanta, Chicago, Manhattan, and Philadelphia. Narrative detail on decision-making and case processing, both generally and in relation to specific types of behavior, including trespassing, retail theft/shoplifting, and simple assault, were coded and analyzed for thematic patterns. Based on the qualitative analysis, this paper offers a conceptual diagram of contexts shaping misdemeanor system interventions among people with mental illnesses., Results: All four sites have been engaged in efforts to reduce the use of misdemeanor charges both generally and in relation to people with mental illnesses. Decision-makers across all sites experience contexts that shape how, when, and where they intervene, which are: (1) law and policy environments; (2) location of the behavior; (3) expectations of stakeholders; (4) knowledge of mental illnesses; and (5) access to community resources. Law and policy environments expand or constrain opportunities for diversion. The location of offending is relevant to who has a stake in the behavior, and what demands they have. Clinical, experiential, and system-level knowledge of mental illnesses inform a chain of decisions about what to do. The capacity to address mental health needs is contingent on access to social services, including housing., Conclusion: People making decisions along the criminal legal continuum are critical to illuminating the dynamic, inter-related contexts that facilitate and frustrate attempts to address defendants' mental health needs while balancing considerations of public safety. Multi-sector, scenario-based or case study exercises could help identify concrete ways of improving each of the contexts that surround whole-of-system decisions., (© 2023. The Author(s).)

Background: We aimed to investigate the effect of non-alcoholic fatty liver disease (NAFLD) on BNT162b2 immunogenicity against wild-type SARS-CoV-2 and variants and infection outcome, as data are lacking., Methods: Recipients of two doses of BNT162b2 were prospectively recruited. Outcomes of interest were seroconversion of neutralizing antibody by live virus microneutralization (vMN) to SARS-CoV-2 strains (wild-type, delta and omicron variants) at day 21, 56 and 180 after first dose. Exposure of interest was moderate-to-severe NAFLD (controlled attenuation parameter ≥ 268 dB/M on transient elastography). We calculated adjusted odds ratio (aOR) of infection with NAFLD by adjusting for age, sex, overweight/obesity, diabetes and antibiotic use., Results: Of 259 BNT162b2 recipients (90 (34.7%) male; median age: 50.8 years (IQR: 43.6-57.8)), 68 (26.3%) had NAFLD. For wild type, there was no difference in seroconversion rate between NAFLD and control groups at day 21 (72.1% vs. 77.0%; p = 0.42), day 56 (100% vs. 100%) and day 180 (100% and 97.2%; p = 0.22), respectively. For the delta variant, there was no difference also at day 21 (25.0% vs. 29.5%; p = 0.70), day 56 (100% vs. 98.4%; p = 0.57) and day 180 (89.5% vs. 93.3%; p = 0.58), respectively. For the omicron variant, none achieved seroconversion at day 21 and 180. At day 56, there was no difference in seroconversion rate (15.0% vs. 18.0%; p = 0.76). NAFLD was not an independent risk factor of infection (aOR: 1.50; 95% CI: 0.68-3.24)., Conclusions: NAFLD patients receiving two doses of BNT162b2 had good immunogenicity to wild-type SARS-CoV-2 and the delta variant but not the omicron variant, and they were not at higher risk of infection compared with controls.

Introduction: The current treatment options for localized prostate cancer are radical prostatectomy and external beam radiotherapy (EBRT) with stereotactic body radiation therapy (SBRT) gaining interest as a treatment option compared to standard fractionation radiation therapy. This present study is a retrospective study evaluating the correlations between the biochemical efficacy, and treatment toxicity in SBRT for localized prostate cancer., Methods: All organ-confined prostate cancer patients treated with SBRT from 2010 to 2018, at Beacon Hospital, Malaysia were included in this study. Patient demographics, dosimetric parameters, and disease information were retrospectively collected. The primary endpoint was biochemical recurrence-free survival assessed using the Phoenix definition (Nadir + 2 ng/mL). Toxicity outcomes were scored using the Radiation Therapy Oncology Group scale., Results: Fourty-nine patients who met the inclusion criteria (5 low-, 13 intermediate- and 31 high-risk according to the D'amico Risk Classification) received SBRT. The most common dose regime was 34-35Gy in 5 fractions (n=18). Other dose regimes were 24Gy in 3 fractions and 25-33Gy in 5 fractions. Median follow-up was 45.4 months. The median pre-treatment prostate-specific antigen (PSA) was 11.22 ng/mL, which decreased to a median PSA of 0.1 ng/mL by 2 years post-treatment. Out of the 49 cases, only 1 case of biochemical recurrence occurred, yielding a 3- and 5-year overall survival of 100%, and a 3- and 5- year biochemical recurrence-free rate of 100% and 95.2%. Acute grade III urinary toxicities occurred in 1 (2%); whereas acute grade I urinary and rectal toxicities were seen in 22 (44.9%) and 7 (14.3%) patients respectively. Grade I and grade III late rectal toxicities occurred in 3 and 1 patients respectively, while 3 and 1 patient reported late grade I and III urethral stricture respectively., Conclusion: SBRT for clinically-localized and locally advanced prostate cancer provided promising outcomes with low toxicity and good biochemical control.

The direct and selective transformation of naturally abundant methane (CH 4 ) into high-value-added oxygenates, e.g., methanol, ethanol, and formic acid, is one of the "Holy Grails" in chemistry and chemical productions. However, complex mixtures of products, often due to over-oxidations, make such transformations highly challenging. Herein, gallium nitride (GaN), a methane-active semiconductor, catalyzes the photooxidation of methane and empowers the fine-controlling of chemoselectivity toward methanol and formic acids, simply by regulating the O 2 content in water. In contrast to previous methods, no overoxidation products (CO 2 and CO) were observed in this process. Mechanistic investigations and the corresponding quantitative experiments indicated that the controllable generation of moderately reactive oxygen radicals (•OOH and •OH) in combination with the direct methane activation triggered by GaN is responsible for the highly selective reactivity and tunability through a photo-generated radical process., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

While existing studies have reported and recognized country-of-origin effects on the intentions to vaccinate against COVID-19 among individual citizens in some countries, the causal mechanism behind such effects to inform public health policymakers remain unexplored. Adding up a quality cue explanation for such effects to the existing literature, the authors argue that individual consumers are less willing to get a vaccine designed and manufactured by a country with a significantly lower quality perception than other countries. A survey experiment that recruited a nationally representative sample of Taiwanese adults (n = 1951) between December 13, 2020 and January 11, 2021 was designed and conducted to test the argument. We find that all else equal, Taiwanese respondents were on average less likely to express stronger willingness to take a vaccine from China than from the US, Germany, and Taiwan. Furthermore, even when the intrinsic quality of the vaccine was held constant by the experimental design, respondents still had a significantly lower quality perception of the vaccine from China, both in terms of perceived protection and severe side effects. Further evidence from casual mediation analyses shows that about 33% and 11% of the total average causal effects of the "China" country-of-origin label on vaccine uptake intention were respectively mediated through the perceived efficacy of protection and perceived risk of experiencing severe side effects. We conclude that quality cue constitutes one of many casual mechanisms behind widely reported country-of-origin effects on intention to vaccinate against COVID-19., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To examine the association between human leukocyte antigen (HLA) and nevirapine (NVP)- and efavirenz (EFV)-induced cutaneous adverse reactions in human immunodeficiency virus (HIV) patients, we conducted a case-control study at our center consisting of 96 patients. Patients were further assigned based on the occurrence of cutaneous adverse events and the drugs involved. All patients were subjected to next generation sequencing (NGS)-based screening with focus on HLA phenotype, including the presence of HLA-B, HLA-C, and HLA-DRB1. Our data indicated that the HLA-C*01:02:01 allele presence was observed in 47.4% (18/38) of patients in the EFV-hypersensitivity group compared with 18.9% (7/30) in the control group [odds ratio (OR) = 5.837; 95% confidence interval (CI) = 1.727-19.722, p  = .005]. In contrast, the occurrence of HLA-DRB1*08:03 was found to be significantly lower in the EFV-hypersensitivity group (4/38, 10.5%) compared with the corresponding control group (12/37, 32.4%) (OR = 0.148; 95% CI = 0.035-0.625, p  = .009). In addition, the HLA-DRB1*04:05:01 antigen was expressed more frequently in the NVP-hypersensitivity group (23.8%, 5/21) compared with the control group (10.8%, 4/37) (OR = 7; 95% CI = 1.265-38.793, p  = .026). Our data not only revealed a significant association between HLA-C*01:02:01 and EFV-induced cutaneous adverse reactions but may also shed light on defining the treatment for Chinese HIV patients.

A copper-catalyzed three-component reaction of ynones, aryl iodides, and elemental sulfur via a syn -addition process is established. The reaction features operational practicality, broad substrate scope, and readily accessible scale-up synthesis by affording a series of ( Z )-1,2-bis(arylthio)alkenes in good to excellent yield. Moreover, benzo[ b ][1,4]dithiines can be also constructed efficiently by using 1,2-diiodobenzene as the coupling partner.

Rationale: Strongyloidiasis is a parasitic disease caused by Strongyloides stercoralis. The clinical presentation varies according to the stage of infection. Diagnosing strongyloidiasis is a challenge in clinical practice due to the inconsistency of eosinophilia and the low sensitivity of standard microscopic stool examination. Strongyloides infection presenting with shock is rare., Patient Concerns: In this case, the condition of a 77-year-old immunocompromised patient with intermittent diarrhea progressed to shock and hypoalbuminemia. Reviewing her medical records, we learned that she had experienced intermittent peripheral eosinophilia during the past 10 months. Although a series of examinations were done, the disease progressed and the diagnosis remained uncertain., Diagnosis: Using standard microscopic stool examination and gastroduodenscopy with biopsy, a diagnosis of strongyloidiasis was made., Interventions: After the diagnosis of strongyloidiasis was made, 2 courses of ivermectin were administered., Outcomes: The patient recovered uneventfully after treatment and there is no recurrence of eosinophilia in 1 year follow-up., Lessons: This report provides a brief review of the current modalities used for diagnosing strongyloidiasis. It emphasizes the low sensitivity of microscopic examination, and highlights the role of gastroduodenoscopy in the diagnosis of strongyloidiasis. This report also assures that patients with strongyloidiasis have a good prognosis when they are treated timely and appropriately., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Three subcategories of high-risk flat and depressed lesions (FDLs), laterally spreading tumors non-granular type (LST-NG), depressed lesions, and large sessile serrated lesions (SSLs), are highly attributable to post-colonoscopy colorectal cancer (CRC). Efficient and organized educational programs on detecting high-risk FDLs are lacking. We aimed to explore whether a web-based educational intervention with training on FIND clues (fold deformation, intensive stool/mucus attachment, no vessel visibility, and demarcated reddish area) may improve the ability to detect high-risk FDLs., Methods: This was an international web-based randomized control trial that enrolled non-expert endoscopists in 13 Asian countries. The participants were randomized into either education or non-education group. All participants took the pre-test and post-test to read 60 endoscopic images (40 high-risk FDLs, five polypoid, 15 no lesions) and answered whether there was a lesion. Only the education group received a self-education program (video and training questions and answers) between the tests. The primary outcome was a detection rate of high-risk FDLs., Results: In total, 284 participants were randomized. After excluding non-responders, the final data analyses were based on 139 participants in the education group and 130 in the non-education group. The detection rate of high-risk FDLs in the education group significantly improved by 14.7% (66.6-81.3%) compared with -0.8% (70.8-70.0%) in the non-education group. Similarly, the detection rate of LST-NG, depressed lesions, and large SSLs significantly increased only in the education group by 12.7%, 12.0%, and 21.6%, respectively., Conclusion: Short self-education focusing on detecting high-risk FDLs was effective for Asian non-expert endoscopists. (UMIN000042348)., (© 2022 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)