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Yi-Ping He, Sheng-Sheng Xu, Ting-Ping Fu, Dan-Na Zhao Shenzhen Second People’s Hospital, Shenzhen, Guangdong, 518037, People’s Republic of ChinaCorrespondence: Yi-Ping He, Shenzhen Second People’s Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong, 518037, People’s Republic of China, Tel +86 0755-83366388, Email he_1324_yipi@yeah.netBackground: With the transformation of China’s economy and society, the floating population has also shown a new development trend, from individual migration to co-migration with family members. In 2020, among the 376 million floating population, the population flowing to cities and towns was 330 million, accounting for nearly 88.1%. The family mobility of the floating population is not just a simple personal gathering or geographical migration, but a profound adjustment of the living environment, social interaction and the interests of family members. Migrants no longer simply play the role of “ urban passers-by”, but gradually move with spouses, children, parents, and even settle in the city, which will inevitably produce different public service and social security needs.Objective: To explore the impact of floating population’s familyization on the participation of medical insurance in the inflow areas.Methods: This study adopted the form of non-systematic literature review. The key words were floating population and medical insurance. The related analysis of PubMed, Embase, CNKI, Wanfang, and VIP databases were reviewed and summarized.Results: Due to the flow between domestic immigrants and regions, their medical insurance is difficult to be guaranteed. The domestic floating population’s demand for health services is increasing, but the coverage of medical services provided by medical insurance is not comprehensive enough.Conclusion: It is necessary to integrate the medical insurance system and improve the adaptability of medical insurance to family mobility; protect the welfare needs of migrant families and increase their willingness to participate in medical insurance at the destination; pay attention to the interaction and integration of floating population families, understand and guide them to participate in the status quo of medical insurance, and improve the status quo.Keywords: domestic migration, health insurance, family mobility

Wei-Fu Chang,1– 3 Ai-Jing Luo,1,3,4 Yi-Feng Yuan,5 Yang Chen,5 Zi-Rui Xin,3,5 Shuai-Shuai Xu1 1Xiangya School of Public Health, Central South University, Changsha 410008, Hunan, People’s Republic of China; 2The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan, People’s Republic of China; 3Key Laboratory of Medical Information Research, Central South University, Changsha 410013, Hunan, People’s Republic of China; 4The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, People’s Republic of China; 5School of Life Sciences, Central South University, Changsha 410013, Hunan, People’s Republic of ChinaCorrespondence: Ai-Jing LuoThe Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Furong District, Changsha 410011, Hunan, People’s Republic of ChinaEmail 574224075@qq.comPurpose: To evaluate the perioperative complications of patients with cervical cancer who are treated with robot-assisted radical hysterectomy (RRH) and to further evaluate the safety of patients undergoing NACT.Methods: A total of 805 consecutive cervical cancer patients undergoing RRH were involved in this report. Their clinical characteristics were retrieved from hospital medical records. Perioperative complications were subdivided into intraoperative and postoperative complications, which were graded according to the Clavien–Dindo classification (CDC), and the complications of grade III and above were defined as severe complications. Furthermore, the two-level logistic regression model was used to estimate the risk factors of perioperative and severe complications and to further confirm the relationship between NACT and perioperative and severe complications.Results: The perioperative complication rate and severe complications were 45.09% and 7.83%, respectively. Poorly differentiated tumor and NACT were identified as independent risk factors for perioperative complications by multifactor analysis. Furthermore, we concentrated on the relations between NACT and complications. The risk of perioperative complications of the group with NACT (OR = 11.08, 95% CI: 5.70– 21.54) was significantly higher than the group without NACT, especially in postoperative complications (OR=17.65, 95% CI: 8.63– 36.08), even after adjusting confounding factors. However, there was no statistically significant difference in terms of severe complications (OR=1.68, 95% CI: 0.64– 4.41) and intraoperative complications (OR=0.51, 95% CI: 0.18– 1.41). Moreover, as the times of NACT increase, the impact on perioperative complications is more pronounced. A similar trend was observed in postoperative complications, while this statistical difference was still not observed in intraoperative and severe complications.Conclusion: This result demonstrates the feasibility and safety of RRH of cervical carcinoma after NACT in generally, since it only causes mild complications, not severe complications.Keywords: cervical carcinoma, robot-assisted radical hysterectomy, neoadjuvant chemotherapy, Clavien–Dindo classification, perioperative complications

Understanding the origin and dynamics of hadron structure and in turn that of atomic nuclei is a central goal of nuclear physics. This challenge entails the questions of how does the roughly 1GeV mass-scale that characterizes atomic nuclei appear; why does it have the observed value; and, enigmatically, why are the composite Nambu-Goldstone (NG) bosons in quantum chromodynamics (QCD) abnormally light in comparison? In this perspective, we provide an analysis of the mass budget of the pion and proton in QCD; discuss the special role of the kaon, which lies near the boundary between dominance of strong and Higgs mass-generation mechanisms; and explain the need for a coherent effort in QCD phenomenology and continuum calculations, in exa-scale computing as provided by lattice QCD, and in experiments to make progress in understanding the origins of hadron masses and the distribution of that mass within them. We compare the unique capabilities foreseen at the electron-ion collider (EIC) with those at the hadron-electron ring accelerator (HERA), the only previous electron-proton collider; and describe five key experimental measurements, enabled by the EIC and aimed at delivering fundamental insights that will generate concrete answers to the questions of how mass and structure arise in the pion and kaon, the Standard Model's NG modes, whose surprisingly low mass is critical to the evolution of our Universe.

An organocatalytic asymmetric vinylogous Michael/oxa-Michael tandem reaction between β,γ-unsaturated pyrazoleamides and isatin-derived β,γ-unsaturated ketoesters has been developed with excellent regio-, diastereo-, and enantioselectivities. The methodology provides an effective approach to construct enantiomerically pure 3,4'-pyranyl spirooxindole derivatives containing three contiguous chiral centers. Moreover, the transformations of the chiral products, including the removal and reduction of the pyrazole group, have been investigated.

Key Message: Robust QTLs conferring resistance to bacterial leaf streak in wheat were mapped on chromosomes 3B and 5A from the variety Boost and on chromosome 7D from the synthetic wheat line W-7984. Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa poses a significant threat to global wheat production. High levels of BLS resistance are rare in hexaploid wheat. Here, we screened 101 diverse wheat genotypes under greenhouse conditions to identify new sources of BLS resistance. Five lines showed good levels of resistance including the wheat variety Boost and the synthetic hexaploid wheat line W-7984. Recombinant inbred populations derived from the cross of Boost × ND830 (BoostND population) and W-7984 × Opata 85 (ITMI population) were subsequently evaluated in greenhouse and field experiments to investigate the genetic basis of resistance. QTLs on chromosomes 3B, 5A, and 5B were identified in the BoostND population. The 3B and 5A QTLs were significant in all environments, but the 3B QTL was the strongest under greenhouse conditions explaining 38% of the phenotypic variation, and the 5A QTL was the most significant in the field explaining up to 29% of the variation. In the ITMI population, a QTL on chromosome 7D explained as much as 46% of the phenotypic variation in the greenhouse and 18% in the field. BLS severity in both populations was negatively correlated with days to heading, and some QTLs for these traits overlapped, which explained the tendency of later maturing lines to have relatively higher levels of BLS resistance. Markers associated with the QTLs were converted to KASP markers, which will aid in the deployment of the QTLs into elite lines for the development of BLS-resistant wheat varieties., Competing Interests: Declarations Conflict of interest The authors have no relevant financial or non-financial interests to disclose. Ethics approval NA. Consent to participate NA. Consent to publish NA., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Septoria nodorum blotch is an important disease of both durum and hard red spring wheat (HRSW) worldwide. The disease is caused by the necrotrophic fungal pathogen Parastagonospora nodorum when compatible gene-for-gene interactions occur between pathogen-produced necrotrophic effectors (NEs) and corresponding host sensitivity genes. To date, nine sensitivity gene-NE interactions have been identified, but there is little information available regarding their overall frequency in durum and HRSW. Here, we infiltrated a global HRSW panel (HRSWP) and the Global Durum Panel (GDP) with P. nodorum NEs SnToxA, SnTox1, SnTox267, SnTox3, and SnTox5. Frequencies of sensitivity to SnTox1 and SnTox5 were higher in durum compared to HRSW and vice versa for SnTox267 and SnTox3. Strong associations for the known sensitivity loci Tsn1, Snn1, Snn2, Snn3, Snn5, and Snn7 along with potentially novel sensitivity loci on chromosome arms 7DS and 3BL associated with SnToxA and SnTox267, respectively, were identified in the HRSWP. In the GDP, Snn1, Snn3, and Snn5 were identified along with novel loci associated with sensitivity to SnTox267 on chromosome arms 2AS, 2AL, and 6AS and with SnTox5 sensitivity on 2BS and 7BL. These results reveal additional NE sensitivity loci beyond those previously described demonstrating a higher level of genetic complexity of the wheat-P. nodorum system than previously thought. Knowledge regarding the prevalence and genomic locations of SNB susceptibility genes in HRSW and durum will prove useful for developing efficient breeding strategies and improving varieties for SNB resistance.

Objective: This study updates a previous paper that examined trends in the sale of cigarettes and heated tobacco products (HTPs) in Japan between 2011 and part way through 2019. The current study includes complete unit sales data through 2023., Methods: Data on cigarette and HTP sales were obtained from public sources available from the websites and stockholder reports for the Tobacco Institute of Japan, Philip Morris International and Japan Tobacco. We used joinpoint regression using the parametric method to test for trends in both per capita and total sales for the three outcome variables assessed between 2011 and 2023: (1) cigarette sales, (2) HTP sales and (3) combined cigarette and HTP sales. Joinpoint regression identifies changes in trends and estimates the annual per cent change (APC) for each trend segment., Results: Between 2011 and 2023, per capita and total cigarette sales declined by 52.6% and 52.7%, respectively. From 2011 to 2015, per capita cigarette sales in Japan decreased -1.5% APC; from 2015 to 2018, the decline accelerated to -10.5% APC and continued to fall -7.3% APC between 2018 and 2023. Between 2016 and 2018, per capita HTP sales increased by 149.0% APC, and since 2018, they have increased by 8.1% APC., Conclusion: While many factors may account for the decreased sale of cigarettes in Japan over the past 12 years, the increased sale of HTPs appears to be a factor., Competing Interests: Competing interests: KMC has been a paid expert witness in litigation against the cigarette industry. MLG received a research grant from Pfizer and served as a member of the scientific advisory board of Johnson & Johnson. GTF has served as an expert witness and consultant for governments defending their country’s tobacco control policies and regulations in litigation, and was and unpaid member of he Health Canada Vaping Products Scientific Advisory Group 2017-2020. All others have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This review summarizes the latest progress in orthopedic nanotechnology, explores innovative applications of nanofibers in tendon repair, and evaluates the potential of selenium and cerium oxide nanoparticles in osteoarthritis and osteoblast differentiation. This review also describes the emerging applications of injectable hydrogels in cartilage engineering, emphasizing the critical role of interdisciplinary research and highlighting the challenges and future prospects of integrating nanotechnology into orthopedic clinical practice. This comprehensive approach provides a holistic perspective on the transformative impact of nanotechnology in orthopedics, offering valuable insights for future research and clinical applications., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: In April 2020, Japan's revised Health Promotion Act (HPA) banned cigarette smoking and heated tobacco products (HTP) use in indoor public places but exempted small establishments and permitted smoking-designated/HTP-designated rooms. This pre-post study evaluated the effectiveness of the HPA., Methods: Data were from waves 1 to 4 (2018-2021) of the International Tobacco Control Japan Surveys among a national cohort of adults who smoke cigarettes, use HTPs and do not use any tobacco products. The sample sizes in the respective surveys were 4615, 4222, 4387 and 4254. Multivariable logistic regression models employing generalised estimating equations estimated the prevalence of observed and self-reported indoor smoking/HTP use in key public venues (restaurants/cafés, bars/pubs and workplaces), smoke-free places, and homes, and smoke-free/HTP aerosol-free home policies (model 1). The models were additionally adjusted for waves 1-4 to estimate the impacts of the HPA (model 2)., Results: The implementation of the HPA significantly reduced observed indoor smoking in bars/pubs (model 1: 82.2% (pre) to 55.5% (post), model 2: p=0.04) but not in restaurants/cafés (model 1: 53.0%-24.9%, model 2: p=0.15) or workplaces (model 1: 35.3%-30.1%, model 2: p=0.62). Observed indoor HTP use was also common postimplementation (restaurants/cafés: 19.6%, bars/pubs: 53.9%, workplaces: 36.4%). The implementation of the HPA was associated with a significant increase in observed HTP use in smoke-free places (model 1: 26.3%-33.3%, model 2: p=0.001) and a suggestive increase in homes without HTP aerosol-free policies among adults who smoke (model 1: 64.0%-77.0%, model 2: p=0.09)., Conclusions: The implementation of the HPA was limited in its effectiveness. Comprehensive regulations with no exemptions are needed in Japan., Competing Interests: Competing interests: GF has served as an expert witness or consultant for governments defending their country’s policies or regulations in litigation. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Hessian fly, Mayetiola destructor (Say) belonging to the order Diptera (family: Cecidomyiidae), is a destructive pest of host wheat (Triticum aestivum L.) causing significant economic losses. Although planting resistant wheat cultivars harboring an effective Hessian fly resistance gene (H) is the most economical and environmentally friendly pest management strategy, it imposes selection pressure on the insect populations and can lead to the evolution of Hessian fly virulence. This results in the eventual failure of the deployed H gene. New sources and novel types of resistance are urgently needed to expand the repertoire of H genes and enable strategies that are more effective and durable over the long-term. New sources of Hessian fly resistance have been identified from tetraploid (T. turgidum L., AABB) and hexaploid (T. aestivum, AABBDD) wheat species, as well as from wheat's D-genome donor (Aegilops tauschii Coss., DD). In contrast, diploid einkorn wheat (T. monococcum L., AA) has not been extensively explored for Hessian fly resistance. In this study, we phenotyped 506 T. monococcum accessions belonging to 2 subspecies, T. monococcum L. subsp. monococcum (205 accessions) and T. monococcum subsp. aegilopoides (Link) Thell. (301 accessions), for resistance against 2 predominant Hessian fly biotypes, L and GP (Great Plains). Three and 6 accessions belonging to subsp. monococcum and aegilopoides, respectively, showed > 70% resistance. These accessions provide additional resources for improving wheat cultivars as mitigating strategies for Hessian fly management., (Published by Oxford University Press on behalf of Entomological Society of America 2024.)

Simnotrelvir (SIM0417), an inhibitor of the 3CL protease of SARS-CoV-2, has been identified as a CYP3A sensitive substrate. This study investigated the pharmacokinetics, metabolism, and mass balance of simnotrelvir following a single oral dose of 750 mg in six healthy Chinese male subjects, co-administered with four doses of 100 mg ritonavir. Analysis using 19 F qNMR combined with LC-MS/MS showed that the parent drug M0 constituted over 90% of the drug-related components in plasma. Of the administered dose, 55.4% (54.3% of M0) was recovered in urine, while 36.7% (4.57% of M0) was excreted in feces. UPLC/Q-TOF MS was used to identify metabolites in human plasma, urine and feces. Notably, oxidative metabolites catalyzed by CYP3A were scarcely detected in these matrixes. The amide hydrolyzed metabolite M9 and the cyano hydrolyzed metabolite M10 were recognized as the predominant metabolites, with the main excretion being through feces (19.0% and 12.7% of the administered dose, respectively). In vitro experiments indicated that M10 is primarily formed in the duodenum and jejunum, with further metabolism to M9 by microbiota in the large intestine. Overall, the co-administration of simnotrelvir with ritonavir led to predominant metabolism by intestinal enzymes or microbiota, resulting in hydrolyzed metabolites. These findings highlight the critical role of intestinal metabolism in the pharmacokinetics of simnotrelvir and emphasize the need to consider interactions with antibiotics and individual differences of intestinal microbiota., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Smokeless tobacco (SLT) packaging in India had a single symbolic (a scorpion) health warning label (HWL) in 2009 covering 40% of the front surface. In 2011, it was replaced with four pictorial images. In 2016, HWLs were enlarged to 85% on the front and back. This study aimed to assess the effectiveness of the old (symbolic and smaller images) and larger HWLs., Methods: Data were from the Tobacco Control Project India Survey and included respondents who used SLT in Wave 1 (2010-2011, n=5911), Wave 2 (2012-2013, n=5613) and Wave 3 (2018-2019, n=5636). Using a repeated-measures design, weighted logistic regression models assessed whether there were changes in seven HWL effectiveness measures within the domains of awareness, salience, cognitive and behavioural responses. A cohort design was employed to test whether HWL effectiveness in Waves 1 and 2 was associated with quitting SLT in Waves 2 and 3, respectively., Results: The 2011 HWL revision did not result in any significant changes in HWL effectiveness. There was no significant change in HWL awareness and salience after larger HWLs were introduced in 2016, but respondents were more likely to consider SLT health risks (Wave 2=17.9%, Wave 3=33.6%, p<0.001) and quitting SLT (Wave 2=18.9%, Wave 3=36.5, p<0.001). There was no change in HWLs stopping SLT use (Wave 2=36.6%, Wave 3=35.2%, p=0.829); however, respondents were more likely to avoid looking at HWLs (Wave 2=10.1%, Wave 3=40.2%, p<0.001). Effectiveness of older, symbolic and smaller pictorial HWLs was not associated with quitting SLT., Discussion: There was no significant change in HWL effectiveness following the revision from a symbolic to a pictorial image, but enlarging pictorial images resulted in some improved cognitive and behavioural effects. Results suggested wear-out of HWL salience and that the effectiveness of warnings depends on both their design and time since implementation., Competing Interests: Competing interests: GF has served as an expert witness or a consultant for governments defending their country’s policies or regulations in litigation. GF and SG served as paid expert consultants to the Ministry of Health of Singapore in reviewing the evidence on plain/standardised packaging. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Since their introduction in 2015, directional leads have practically replaced conventional leads for deep brain stimulation (DBS) in Parkinson's disease (PD). Yet, the benefits of directional DBS (dDBS) over omnidirectional DBS (oDBS) remain unclear. This meta-analysis and systematic review compares the literature on dDBS and oDBS for PD., Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Database searches included Pubmed, Cochrane (CENTRAL) and EmBase, using relevant keywords such as 'directional', 'segmented', 'brain stimulation' and 'neuromodulation'. The screening was based on the title and abstract., Results: 23 papers reporting on 1273 participants (1542 leads) were included. The therapeutic window was 0.70 mA wider when using dDBS (95% CI 0.13 to 1.26 mA, p=0.02), with a lower therapeutic current (0.41 mA, 95% CI 0.27 to 0.54 mA, p=0.01) and a higher side-effect threshold (0.56 mA, 95% CI 0.38 to 0.73 mA, p<0.01). However, there was no relevant difference in mean Unified Parkinson's Disease Rating Scale III change after dDBS (45.8%, 95% CI 30.7% to 60.9%) compared with oDBS (39.0%, 95% CI 36.9% to 41.2%, p=0.39), in the medication-OFF state. Median follow-up time for dDBS and oDBS studies was 6 months and 3 months, respectively (range 3-12 for both). The use of directionality often improves dyskinesia, dysarthria, dysesthesia and pyramidal side effects. Directionality was used in 55% of directional leads at 3-6 months, remaining stable over time (56% at a mean of 14.1 months)., Conclusions: These findings suggest that stimulation parameters favour dDBS. However, these do not appear to have a significant impact on motor scores, and the availability of long-term data is limited. dDBS is widely accepted, but clinical data justifying its increased complexity and cost are currently sparse., Prospero Registration Number: CRD42023438056., Competing Interests: Competing interests: MK is a consultant for Boston Scientific, Brainlab and Elekta and has received travel and research funding from Medtronic. LZ is a consultant for Boston Scientific, Medtronic and Brainlab., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Simnotrelvir is a small-molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp. Hence, the drug-drug interaction potential of simnotrelvir/ritonavir should be investigated., Methods: This drug-drug interaction study was an open-label, fixed-sequence, two-period phase I clinical trial in Chinese healthy adult subjects, divided into three cohorts, including simnotrelvir/ritonavir co-administrated with a strong CYP3A and P-gp inhibitor (itraconazole) and inducer (rifampicin), and with a specific CYP3A substrate (midazolam)., Results: The results demonstrated that compared with administration of simnotrelvir/ritonavir alone, the co-administration with itraconazole increased the geometric least-square mean ratio (GMR) of the expose (area under the plasma concentration-time curve from time zero to the lowest detectable plasma concentration [AUC 0-t ]) of simnotrelvir by 25% (GMR 125%, 90% CI 114-137%), whereas co-administration with rifampicin significantly decreased the AUC 0-t of simnotrelvir by 81.5% (GMR 18.5%, 90% CI 16.4-20.9%). Notably, simnotrelvir/ritonavir increased the AUC 0-t of midazolam by 16.69-fold (GMR 1769%, 90% CI 1551-2018%). The co-administration of simnotrelvir/ritonavir and rifampicin caused the increased amount and severity of treatment-emergent adverse events, especially hepatotoxicity., Discussion: The co-administration of simnotrelvir/ritonavir with CYP3A and P-gp inhibitors can be safely used, whereas the co-administration with CYP3A and P-gp strong inducer should be avoided to minimize the risk of under-exposure. Co-administration of midazolam with simnotrelvir/ritonavir increased systemic exposure of midazolam., Clinicaltrials: gov Identifier: NCT05665647., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Freezing of gait (FOG) is a disabling and heterogeneous symptom in patients with Parkinson's disease (PD). Among them, dopamine-induced FOG is rare and difficult to identify. The treatment of dopamine-induced FOG is complex., Case Presentation: We herein presented a case of PD patient who complicated with refractory FOG. It was identified as dopamine-induced FOG during levodopa challenge test. Her symptoms were alleviated after we reduced the total equivalent dosage of levodopa., Conclusion: Our report emphasizes the importance of levodopa challenge test in identifying different types of FOG, which is very important for further adjusting treatment., 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 © 2024 Xu, Zhu, Yuan, Zeng, Li, Liu, Huang, Zhang and Wang.)

Bread wheat (Triticum aestivum) is a globally dominant crop and major source of calories and proteins for the human diet. Compared with its wild ancestors, modern bread wheat shows lower genetic diversity, caused by polyploidisation, domestication and breeding bottlenecks 1,2 . Wild wheat relatives represent genetic reservoirs, and harbour diversity and beneficial alleles that have not been incorporated into bread wheat. Here we establish and analyse extensive genome resources for Tausch's goatgrass (Aegilops tauschii), the donor of the bread wheat D genome. Our analysis of 46 Ae. tauschii genomes enabled us to clone a disease resistance gene and perform haplotype analysis across a complex disease resistance locus, allowing us to discern alleles from paralogous gene copies. We also reveal the complex genetic composition and history of the bread wheat D genome, which involves contributions from genetically and geographically discrete Ae. tauschii subpopulations. Together, our results reveal the complex history of the bread wheat D genome and demonstrate the potential of wild relatives in crop improvement., (© 2024. The Author(s).)

This study was designed to evaluate the diagnostic efficacy of relevant parameters of 18 F-prostate-specific membrane antigen (PSMA)-1007 PET/CT in predicting the pathological grade of primary prostate cancer. Briefly, a prospective analysis was performed on 53 patients diagnosed with prostate cancer by systematic puncture biopsy, followed by 18 F-PSMA-1007 PET/CT examination prior to treatment within 10 d. The patients were grouped in accordance with the Gleason grading system revised by the International Association of Urology Pathology (ISUP). They were divided into high-grade group (ISUP 4-5 group) and low-grade group (ISUP 1-3 group). The differences in maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), intraprostatic PSMA-derived tumor volume (iPSMA-TV), and intraprostatic total lesion PSMA (iTL-PSMA) between the high- and low-grade group were statistically significant ( p  < .001). No significant difference was found for mean standardized uptake value (SUVmean) between the high- and low-grade groups (Z =  -1.131, p  = .258). Besides, binary multivariate logistic regression analysis showed that only iPSMA-TV and iTL-PSMA were independent predictors of the pathological grading, for which the odds ratios were 18.821 [95% confidence interval (CI): 2.040-173.614, p  = .010] and 0.758 (95% CI: 0.613-0.938, p  = .011), respectively. The area under the ROC of this regression model was 0.983 (95% CI: 0.958-1.00, p  < .001). Only iTL-PSMA was a significant parameter for distinguishing ISUP-4 and ISUP-5 groups (Z =  -2.043, p  = .041). In a nutshell, 18 F-PSMA-1007 PET/CT has good application value in predicting the histopathological grade of primary prostate cancer. Three-dimensional volume metabolism parameters iPSMA-TV and iTL-PSMA were found to be independent predictors for pathological grade.

Objective: This study aimed to initially adopt an International Healthy Eating Report Card for Preschool-Aged Children to assess the prevalence of healthy eating behaviours and favourable family home food environments (FHFEs) among preschool-aged children in Australia, Hong Kong, Singapore, and the US. We also examined which cultural contexts would exhibit significant differences in the report card scores among the four cultural contexts., Methods: In this cross-cultural study, 2059 parent-child dyads, with approximately 500 dyads in each cultural context, were recruited. The parents were asked to complete the validated International Healthy Eating Report Card Scale to assess the dimensions of the Report Card [i.e., Indicator of Children's Eating Behaviours: (1) Children's Dietary Patterns and (2) Children's Mealtime Behaviours, and Indicator of FHFEs: (3) Parental Food Choices and Preparation, (4) Home Healthier Food Availability and Accessibility and (5) Family Mealtime Environments]. Each indicator received a letter grade [i.e., A (≥80%) = excellent, B (60-79%) = good, C (40-59%) = fair, D (20-39%) = poor, F (<20%) = very poor and including the plus (+) and minus (-) signs] to represent the proportion of participants who could meet the predefined benchmarks. We also employed ANCOVA and Bonferroni's post-hoc test to examine the differences in the report card scores between the four cultural contexts. A significance level was set at p  < 0.05., Results: The average overall report card grade across the four cultural contexts was "B-" (Good), ranging from "C+" (Singapore and the US) to "B-" (Australia and Hong Kong). The average grade for Children's Eating Behaviours was classified as Fair ("C-"), while the average grade for FHFEs was classified as Good ("B+") for all cultural contexts. A comparison of the overall report card scores revealed that Australia exhibited a significantly higher report card score than Singapore and the US, while Hong Kong achieved a significantly higher score than Singapore., Conclusion: The International Healthy Eating Report Card provided an overview of the prevalence of healthy eating in different cultural contexts. We believe that the International Healthy Eating Report Card may offer new perspectives on interventions for fostering healthy eating in young children., 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 © 2024 Wan, Chung, Li, Xu and Chan.)

Genetic variants in genes encoding subunits of the γ-aminobutyric acid-A receptor (GABA A R) have been found to cause neurodevelopmental disorders and epileptic encephalopathy. In a patient with epilepsy and developmental delay, a de novo heterozygous missense mutation c.671 T > C (p.F224S) was discovered in the GABRB2 gene, which encodes the β2 subunit of GABA A R. Based on previous studies on GABRB2 variants, this new GABRB2 variant (F224S) would be pathogenic. To confirm and investigate the effects of this GABRB2 mutation on GABA A R channel function, we conducted transient expression experiments using GABA A R subunits in HEK293T cells. The GABA A Rs containing mutant β2 (F224S) subunit showed poor trafficking to the cell membrane, while the expression and distribution of the normal α1 and γ2 subunits were unaffected. Furthermore, the peak current amplitude of the GABA A R containing the β2 (F224S) subunit was significantly smaller compared to the wild type GABA A R. We propose that GABRB2 variant F224S is pathogenic and GABA A Rs containing this β2 mutant reduce response to GABA under physiological conditions, which could potentially disrupt the excitation/inhibition balance in the brain, leading to epilepsy., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Septoria nodorum blotch (SNB), caused by Parastagonospora nodorum, is a disease of durum and common wheat initiated by the recognition of pathogen-produced necrotrophic effectors (NEs) by specific wheat genes. The wheat gene Snn1 was previously cloned, and it encodes a wall-associated kinase that directly interacts with the NE SnTox1 leading to programmed cell death and ultimately the development of SNB. Here, sequence analysis of Snn1 from 114 accessions including diploid, tetraploid, and hexaploid wheat species revealed that some wheat lines possess two copies of Snn1 (designated Snn1-B1 and Snn1-B2) approximately 120 kb apart. Snn1-B2 evolved relatively recently as a paralog of Snn1-B1, and both genes have undergone diversifying selection. Three point mutations associated with the formation of the first SnTox1-sensitive Snn1-B1 allele from a primitive wild wheat were identified. Four subsequent and independent SNPs, three in Snn1-B1 and one in Snn1-B2, converted the sensitive alleles to insensitive forms. Protein modeling indicated these four mutations could abolish Snn1-SnTox1 compatibility either through destabilization of the Snn1 protein or direct disruption of the protein-protein interaction. A high-throughput marker was developed for the absent allele of Snn1, and it was 100% accurate at predicting SnTox1-insensitive lines in both durum and spring wheat. Results of this study increase our understanding of the evolution, diversity, and function of Snn1-B1 and Snn1-B2 genes and will be useful for marker-assisted elimination of these genes for better host resistance., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Key Message: A total of 65 SNPs associated with resistance to tan spot and septoria nodorum blotch were identified in a panel of 180 cultivated emmer accessions through association mapping Tan spot and septoria nodorum blotch (SNB) are foliar diseases caused by the respective fungal pathogens Pyrenophora tritici-repentis and Parastagonospora nodorum that affect global wheat production. To find new sources of resistance, we evaluated a panel of 180 cultivated emmer wheat (Triticum turgidum ssp. dicoccum) accessions for reactions to four P. tritici-repentis isolates Pti2, 86-124, 331-9 and DW5, two P. nodorum isolate, Sn4 and Sn2000, and four necrotrophic effectors (NEs) produced by the pathogens. About 8-36% of the accessions exhibited resistance to the four P. tritici-repentis isolates, with five accessions demonstrating resistance to all isolates. For SNB, 64% accessions showed resistance to Sn4, 43% to Sn2000 and 36% to both isolates, with Spain (11% accessions) as the most common origin of resistance. To understand the genetic basis of resistance, association mapping was performed using SNP (single nucleotide polymorphism) markers generated by genotype-by-sequencing and the 9 K SNP Infinium array. A total of 46 SNPs were significantly associated with tan spot and 19 SNPs with SNB resistance or susceptibility. Six trait loci on chromosome arms 1BL, 3BL, 4AL (2), 6BL and 7AL conferred resistance to two or more isolates. Known NE sensitivity genes for disease development were undetected except Snn5 for Sn2000, suggesting novel genetic factors are controlling host-pathogen interaction in cultivated emmer. The emmer accessions with the highest levels of resistance to the six pathogen isolates (e.g., CItr 14133-1, PI 94634-1 and PI 377672) could serve as donors for tan spot and SNB resistance in wheat breeding programs., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Powdery mildew, caused by the fungal pathogen Blumeria graminis (DC.) E. O. Speer f. sp. tritici Em. Marchal (Bgt), is a constant threat to global wheat (Triticum aestivum L.) production. Although ∼100 powdery mildew (Pm) resistance genes and alleles have been identified in wheat and its relatives, more is needed to minimize Bgt's fast evolving virulence. In tetraploid wheat (Triticum turgidum L.), wild emmer wheat [T. turgidum ssp. dicoccoides (Körn. ex Asch. & Graebn.) Thell.] accessions from Israel have contributed many Pm resistance genes. However, the diverse genetic reservoirs of cultivated emmer wheat [T. turgidum ssp. dicoccum (Schrank ex Schübl.) Thell.] have not been fully exploited. In the present study, we evaluated a diverse panel of 174 cultivated emmer accessions for their reaction to Bgt isolate OKS(14)-B-3-1 and found that 66% of accessions, particularly those of Ethiopian (30.5%) and Indian (6.3%) origins, exhibited high resistance. To determine the genetic basis of Bgt resistance in the panel, genome-wide association studies were performed using 46,383 single nucleotide polymorphisms (SNPs) from genotype-by-sequencing and 4331 SNPs from the 9K SNP Infinium array. Twenty-five significant SNP markers were identified to be associated with Bgt resistance, of which 21 SNPs are likely novel loci, whereas four possibly represent emmer derived Pm4a, Pm5a, PmG16, and Pm64. Most novel loci exhibited minor effects, whereas three novel loci on chromosome arms 2AS, 3BS, and 5AL had major effect on the phenotypic variance. This study demonstrates cultivated emmer as a rich source of powdery mildew resistance, and the resistant accessions and novel loci found herein can be utilized in wheat breeding programs to enhance Bgt resistance in wheat., (© 2024 The Author(s). The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: Teprotumumab plays an important role in thyroid eye disease pathogenesis and progression. We intend to mine the adverse event (AE) signals from a relevant database, thereby contributing to the safe use of teprotumumab., Methods: The data obtained from the ASCII data packages in the FAERS database from January 2020 to the second quarter of 2023 were imported into the SAS software (version 9.4) for data cleaning and analysis. Disproportionality analysis was performed using the reporting odds ratio (ROR) in conjunction with the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) omnibus standard method to detect positive signals., Participants: This retrospective observational study relied on adverse drug reactions reported to the FDA through FAERS, which is a standard public system for spontaneous reporting., Results: Collectively, 2171 AE reports for teprotumumab were collected, among which 108 significant signals were identified involving 17 system organ classes. The SOC of ear and labyrinth disorders included the most AE signals and reports. Muscle spasms, fatigue, headache, nausea, diarrhea, alopecia, blood glucose increased, hypoacusis, tinnitus, and diabetes mellitus were the top ten PTs ranked by the frequency of reporting, meanwhile, the two high-strength signals of thyroid-stimulating immunoglobulin increase (ROR 662.89, 95% CI 182.40-2409.19) and gingival recession (ROR 125.13, 95% CI 79.70-196.45) were not documented in the drug instruction. Meanwhile, we found a higher risk of increased blood glucose, deafness, and decreased appetite for male patients, and headache for female patients., Conclusions: Clinical application of teprotumumab should be closely monitored for ototoxicity, nail abnormalities, and menstrual changes, as well as for AEs not mentioned in the drug instruction, including gingival recession, thyroid-stimulating immunoglobulin increase, and so on., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19., Methods: We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications., Results: 56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58-0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59-0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69-0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26-1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50-0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76-0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62-0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81-0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79-0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12-1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography., Conclusion: Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies., (© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Background: However, the connection between smoking and the prognosis of patients with bladder cancer remains unclear., Aim: To determine whether smoking is linked to the recurrence and progression of bladder cancer., Methods: As of July 20, 2022, relevant English-language research was identified by searching PubMed, the Web of Science, and the Cochrane Library. We pooled the available data from the included studies using a random effects model. Subgroup analysis and sensitivity analysis were also conducted., Results: A total of 12 studies were included in this meta-analysis. The combined analysis revealed that tobacco exposure was associated with a significantly greater recurrence rate than nonsmoking status [odd ratios (OR) = 1.76, 95%CI: 1.84-2.93], and the progression of bladder cancer was significantly greater in smokers than in nonsmokers (OR = 1.21, 95%CI: 1.02-1.44). Stratified analysis further revealed that current smokers were more likely to experience relapse than never-smokers were (OR = 1.85, 95%CI: 1.11-3.07). Former smokers also had a greater risk of relapse than did never-smokers (OR = 1.73, 95%CI: 1.09-2.73). Subgroup analysis indicated that non-Caucasians may be more susceptible to bladder cancer recurrence than Caucasians are (OR = 2.13, 95%CI: 1.74-2.61)., Conclusion: This meta-analysis revealed that tobacco exposure may be a significant risk factor for both the recurrence and progression of bladder cancer., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest related to this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Dual use of e-cigarettes and cigarettes is a growing usage pattern in adults, but little is known about the motivations underlying this trend. We investigated the reasons for e-cigarette use among adults who smoke, considering variation in sociodemographic subgroups., Methods: This repeated cross-sectional study analysed adults who smoked at least weekly and vaped at any frequency. Data were from the International Tobacco Control Korea Surveys conducted in 2016 (n=164) and 2020 (n=1088). Fourteen reasons for e-cigarette use were assessed in both waves. Subgroup analyses were performed by age, sex and educational level., Results: The top reasons for e-cigarette use in 2020 were curiosity (62.8%), less harmful than smoking (45.4%) and taste (43.2%). Curiosity was the most cited across age, sex and education subgroups. Significant differences were observed in 2020 compared with 2016, with lower percentages in goal-oriented reasons: helping quit smoking (36.3% vs 48.9%; p=0.017), helping cut down smoking (35.3% vs 52.7%; p=0.001), less harmful to others (39.0% vs 54.6%; p=0.003) and more acceptable (31.6% vs 61.2%; p<0.001). By contrast, non-goal-oriented reasons showed higher percentages in 2020, such as curiosity (62.8% vs 27.9%; p<0.001), taste (43.2% vs 22.1%; p<0.001) and enjoyment (26.8% vs 8.6%; p<0.001). In 2020, a majority of adults who smoked and vaped (53.3%) reported no intention to quit or reduce smoking., Conclusions: E-cigarette use for curiosity and pleasure predominated among adults who smoked. The reasons for dual use in adults have shifted from goal-oriented to non-goal-oriented., Competing Interests: Competing interests: GTF has served as an expert witness or consultant for governments defending their country’s policies or regulations in litigation. All other authors have no competing interest to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Arsenic (As) is a notorious environmental toxicant widely present in various natural environments. As exposure has been correlated with the decline in sperm motility. Yet, the mechanism has not been fully elucidated. Adult male C57 mice were given 0, 1, or 15 mg/L NaAsO 2 for 10 weeks. The mature seminiferous tubules and sperm count were decreased in As-exposed mice. Sperm motility and several sperm motility parameters, including average path velocity (VAP), straight-line velocity (VSL), curvilinear velocity (VCL), beat-cross frequency (BCF), linearity (LIN), straightness (STR), and amplitude of lateral head displacement (ALH), were declined in As-exposed mice. RNA sequencing and transcriptomics analyses revealed that differentially expressed genes (DEGs) were mainly enriched in metabolic pathways. Untargeted metabolomics analyses indicated that energy metabolism was disrupted in As-exposed mouse testes. Gene set enrichment analysis showed that glycolysis and oxidative phosphorylation were disturbed in As-exposed mouse testes. As-induced disruption of testicular glucose metabolism and oxidative phosphorylation was further validated by RT-PCR and Western blotting. In conclusion, As exposure causes decline in sperm motility accompanied by energy metabolism disorders in mouse testes., 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. Published by Elsevier Ltd.)

This article is a comprehensive study based on research on the connection between diabetes mellitus (DM) and prostate cancer (PCa). It investigates the potential role of DM as an independent risk factor for PCa, delving into the biological links, including insulin resistance and hormonal changes. The paper critically analyzes previous studies that have shown varying results and introduces mendelian randomization as a method for establishing causality. It emphasizes the importance of early DM screening and lifestyle modifications in preventing PCa, and proposes future research directions for further under-standing the DM - PCa relationship., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)