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Introduction: Cranial electrotherapy stimulation (CES) is beneficial in reducing anxiety in psychiatric patients. However, no studies have reported on elderly patients with generalized anxiety disorders (GAD). This study aimed to determine the efficacy and safety of a 6-week CES intervention for late-life GAD. Materials and methods: This single-arm pilot study assessed 6-week CES treatment (Alpha-Stim AID) for late-life GAD and 4-week follow-up post intervention. The Hamilton Rating Scale for Anxiety (HAMA) and Beck Anxiety Inventory (BAI) were used as baseline and outcome measures at weeks 4, 6, and 10, respectively. Treatment response was defined as 50 % or more reduction of the HAMA score and remission was defined as a of score ≤7 on the HAMA. Other measures included depression, sleep quality, and quality of life assessment. Results: We included participants (n = 27) aged 68.0 ± 5.0 years, 81.5 % of whom were female. Fifteen (55.6 %), 18 (66.7 %), and 15 (55.6 %) patients were concurrently treated with antidepressants, BZDs, and antipsychotics, respectively. Intention-to-treat (ITT) analysis revealed a significant decrease in HAMA scores from baseline (20.96 ± 3.30) to week 6 (12.26 ± 7.09) and one-month (12.85 ± 7.08) follow-up at W10 (all p

Abstract Background Entrustable Professional Activities (EPA)-based assessment is easily and intuitively used in evaluating the learning outcomes of competency-based medical education (CBME). This study aimed to develop an EPA for occupational therapy focused on providing health education and consultation (TP-EPA3) and examine its validity. Methods Nineteen occupational therapists who had completed online training on the EQual rubric evaluation participated in this study. An expert committee identified six core EPAs for pediatric occupational therapy. TP-EPA3 was developed following the EPA template and refined through consensus meetings. The EQual rubric, a 14-item, five-point criterion-based anchor system, encompassing discrete units of work (DU), entrustable, essential, and important tasks of the profession (EEIT), and curricular role (CR), was used to evaluate the quality of TP-EPA3. Overall scores below 4.07, or scores for DU, EEIT, and CR domains below 4.17. 4.00, and 4.00, respectively, indicate the need for modifications. Results The TP-EPA3 demonstrated good validity, surpassing the required cut-off score with an average overall EQual score of 4.21 (SD = 0.41). Specific domain scores for DU, EEIT, and CR were 3.90 (SD = 0.69), 4.46 (SD = 0.44), and 4.42 (SD = 0.45), respectively. Subsequent revisions clarified observation contexts, enhancing specificity and focus. Further validation of the revised TP-EPA3 and a thorough examination of its reliability and validity are needed. Conclusion The successful validation of TP-EPA3 suggests its potential as a valid assessment tool in occupational therapy education, offering a structured approach for developing competency in providing health education and consultation. This process model for EPA development and validation can guide occupational therapists in creating tailored EPAs for diverse specialties and settings.

Abstract Diabetes mellitus affected more than 500 million of people globally, with an annual mortality of 1.5 million directly attributable to diabetic complications. Oxidative stress, in particularly in post-prandial state, plays a vital role in the pathogenesis of the diabetic complications. However, oxidative status marker is generally poorly characterized and their mechanisms of action are not well understood. In this work, we proposed a new framework for deep characterization of oxidative stress in erythrocytes (and in urine) using home-built micro-scale NMR system. The dynamic of post-prandial oxidative status (against a wide variety of nutritional load) in individual was assessed based on the proposed oxidative status of the red blood cells, with respect to the traditional risk-factors such as urinary isoprostane, reveals new insights into our understanding of diabetes. This new method can be potentially important in drafting guidelines for sub-stratification of diabetes mellitus for clinical care and management.

Abstract This study aimed to investigate the association between obesity and herpes zoster (HZ) occurrence. This study used data covering 2 million people in Taiwan in 2000, which were obtained from the National Health Insurance Research Database. The cohort study observed aged 20–100 years with obesity from 2000 to 2017 (tracking to 2018). Obesity was indicated by the presence of two or more outpatient diagnoses or at least one admission record. And, obesity was categorized into non-morbid obesity and morbid obesity. Patients with HZ before the index date were excluded. The obesity cohort and control cohort were matched 1:1 according to age, sex, comorbidities, and index year. There were 18,855 patients in both the obesity and control cohorts. The obesity cohort [adjusted hazard ratio (aHR) 1.09] had a higher risk of HZ than the control cohort. Further analysis, the morbid obesity group (aHR 1.47), had a significantly higher risk of HZ than the non-morbid obesity group. Among the patients without any comorbidities, the patients with obesity had a significantly higher risk of developing HZ than the patients without obesity (aHR 1.18). Obese patients are at a higher risk of HZ development, especially in the patients with morbid obesity. Weight reduction is critical for preventing the onset of chronic diseases and decreasing the risk of HZ in patients with obesity.

Abstract Cryptophytes are ancestral photosynthetic organisms evolved from red algae through secondary endosymbiosis. They have developed alloxanthin-chlorophyll a/c2-binding proteins (ACPs) as light-harvesting complexes (LHCs). The distinctive properties of cryptophytes contribute to efficient oxygenic photosynthesis and underscore the evolutionary relationships of red-lineage plastids. Here we present the cryo-electron microscopy structure of the Photosystem II (PSII)–ACPII supercomplex from the cryptophyte Chroomonas placoidea. The structure includes a PSII dimer and twelve ACPII monomers forming four linear trimers. These trimers structurally resemble red algae LHCs and cryptophyte ACPI trimers that associate with Photosystem I (PSI), suggesting their close evolutionary links. We also determine a Chl a-binding subunit, Psb-γ, essential for stabilizing PSII–ACPII association. Furthermore, computational calculation provides insights into the excitation energy transfer pathways. Our study lays a solid structural foundation for understanding the light-energy capture and transfer in cryptophyte PSII–ACPII, evolutionary variations in PSII–LHCII, and the origin of red-lineage LHCIIs.

Abstract Background Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. Methods We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. Results The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. Conclusion Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

Abstract Multiferroic materials, which simultaneously exhibit ferroelectricity and magnetism, have attracted substantial attention due to their fascinating physical properties and potential technological applications. With the trends towards device miniaturization, there is an increasing demand for the persistence of multiferroicity in single-layer materials at elevated temperatures. Here, we report high-temperature multiferroicity in single-layer CuCrSe2, which hosts room-temperature ferroelectricity and 120 K ferromagnetism. Notably, the ferromagnetic coupling in single-layer CuCrSe2 is enhanced by the ferroelectricity-induced orbital shift of Cr atoms, which is distinct from both types I and II multiferroicity. These findings are supported by a combination of second-harmonic generation, piezo-response force microscopy, scanning transmission electron microscopy, magnetic, and Hall measurements. Our research provides not only an exemplary platform for delving into intrinsic magnetoelectric interactions at the single-layer limit but also sheds light on potential development of electronic and spintronic devices utilizing two-dimensional multiferroics.

Abstract RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B’s involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.

Abstract Background The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes. Results In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50–9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench. Conclusions Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench. Video Abstract

Abstract Background MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), original found in synthetic heroin, causes Parkinson’s disease (PD) in human through its metabolite MPP+ by inhibiting complex I of mitochondrial respiratory chain in dopaminergic neurons. This study explored whether yeast internal NADH-quinone oxidoreductase (NDI1) has therapeutic effects in MPTP- induced PD models by functionally compensating for the impaired complex I. MPP+-treated SH-SY5Y cells and MPTP-treated mice were used as the PD cell culture and mouse models respectively. The recombinant NDI1 lentivirus was transduced into SH-SY5Y cells, or the recombinant NDI1 adeno-associated virus (rAAV5-NDI1) was injected into substantia nigra pars compacta (SNpc) of mice. Results The study in vitro showed NDI1 prevented MPP+-induced change in cell morphology and decreased cell viability, mitochondrial coupling efficiency, complex I-dependent oxygen consumption, and mitochondria-derived ATP. The study in vivo revealed that rAAV-NDI1 injection significantly improved the motor ability and exploration behavior of MPTP-induced PD mice. Accordingly, NDI1 notably improved dopaminergic neuron survival, reduced the inflammatory response, and significantly increased the dopamine content in striatum and complex I activity in substantia nigra. Conclusions NDI1 compensates for the defective complex I in MPP+/MPTP-induced models, and vastly alleviates MPTP-induced toxic effect on dopaminergic neurons. Our study may provide a basis for gene therapy of sporadic PD with defective complex I caused by MPTP-like substance.

Abstract Controlling the direction of ferromagnetism and antiferromagnetism by an electric field in single-phase multiferroics will open the door to the next generation of devices for spintronics and electronics. The typical magnetoelectric coupling such as the linear magnetoelectric effect is very weak in type-I multiferroics and therefore the magnetoelectric switching is rarely achieved. Here, using first-principles simulations, we propose a magnetoelectric switching mechanism to achieve such highly desired control in orthorhombic multiferroics. One class of two-dimensional proper multiferroics (CrX 2Se3 and MnX 2Te3, X = Sn, Ge) and perovskite multiferroics (EuTiO3 and BiFeO3/LaFeO3 superlattice) are taken as examples to show the mechanism. In the ferroelectric switching process, the proper polarization rotates its direction by 180° and keeps its magnitude almost unchanged, the ferromagnetic or antiferromagnetic vector is rotationally switched by 180° following the rotation of ferroelectric polarization. This rotational magnetoelectric switching results from in-plane structural anisotropy and magnetic anisotropy, and the process of switching is governed by c o s i n e functions from the phenomenological Landau-type models. This study addresses the challenge of magnetoelectric switching in type-I multiferroics by proposing a general magnetoelectric switching mechanism.

Abstract Background Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. Main text This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. Conclusions By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health. Graphical Abstract

Abstract Cell type annotation and lineage construction are two of the most critical tasks conducted in the analyses of single-cell RNA sequencing (scRNA-seq). Four recent scRNA-seq studies of differentiating xylem propose four models on differentiating xylem development in Populus. The differences are mostly caused by the use of different strategies for cell type annotation and subsequent lineage interpretation. Here, we emphasize the necessity of using in situ transcriptomes and anatomical information to construct the most plausible xylem development model.

Abstract Background The oral health of older people is closely related to their overall health. Timely and effective intervention in oral issues is necessary to maintain their overall health. This study aimed to evaluate the feasibility and effectiveness of an Oral Health Promotion Program (OHPP) in Geriatric Care Facilities (GCFs). Methods The OHPP was implemented in two GCFs and evaluated using a pre/post-design. Questionnaires on self-efficacy and attitude for providing oral care were sent to 42 nurse participants before and three months after the implementation of the OHPP. Outcomes of 295 patient participants were assessed at four time points (T1-baseline, T2-one month, T3-two months, and T4-three months post-implementation) including Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE), and Oral Health Assessment Tool (OHAT). Results The oral health and daily activity ability of patient participants showed an improving trend at four time points pre/post-implementation of the OHPP. The proportion of patients with healthy mouths (OHAT: 0–3 points) increased from 29.8 to 67.8% and their scores of OHAT and ADL were significantly better at T4 compared to T1, T2, and T3 (p

Abstract Symbiodinium are the photosynthetic endosymbionts for corals and play a vital role in supplying their coral hosts with photosynthetic products, forming the nutritional foundation for high-yield coral reef ecosystems. Here, we determine the cryo-electron microscopy structure of Symbiodinium photosystem I (PSI) supercomplex with a PSI core composed of 13 subunits including 2 previously unidentified subunits, PsaT and PsaU, as well as 13 peridinin-Chl a/c-binding light-harvesting antenna proteins (AcpPCIs). The PSI–AcpPCI supercomplex exhibits distinctive structural features compared to their red lineage counterparts, including extended termini of PsaD/E/I/J/L/M/R and AcpPCI-1/3/5/7/8/11 subunits, conformational changes in the surface loops of PsaA and PsaB subunits, facilitating the association between the PSI core and peripheral antennae. Structural analysis and computational calculation of excitation energy transfer rates unravel specific pigment networks in Symbiodinium PSI–AcpPCI for efficient excitation energy transfer. Overall, this study provides a structural basis for deciphering the mechanisms governing light harvesting and energy transfer in Symbiodinium PSI–AcpPCI supercomplexes adapted to their symbiotic ecosystem, as well as insights into the evolutionary diversity of PSI–LHCI among various photosynthetic organisms.

Abstract Background and purpose The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION). Materials and methods This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7–14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement. Results No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up (p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7–14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups (p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 (p = 0.045). Conclusion Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact.

Abstract Background The atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism. Methods Participants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis. Results 398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90–1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99–1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01–2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03–2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables. Conclusions In middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism.

Abstract Recent studies have suggested that ferroptosis participates in various renal diseases. However, its effect on focal segmental glomerulosclerosis remains unclear. This study analyzed the GSE125779 and GSE121211 datasets to identify the differentially expressed genes (DEGs) in renal tubular samples with and without FSGS. The Cytoscape was used to construct the protein–protein interaction network. Moreover, the ferroptosis-related genes (FRGs) were obtained from the ferroptosis database, while ferroptosis-related DEGs were obtained by intersection with DEGs. The target genes were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The GSE108112 dataset was used to verify the expression of target FRGs. Besides, we built the mRNA-miRNA network regarding FRGs using the NetworkAnalyst database, and circRNAs corresponding to key miRNAs were predicted in the ENCORI database. In this study, 16 ferroptosis-related DEGs were identified between FSGS and healthy subjects, while five co-expressed genes were obtained by three topological algorithms in Cytoscape. These included the most concerned Hub genes JUN, HIF1A, ALB, DUSP1 and ATF3. The KEGG enrichment analysis indicated that FRGs were associated with mitophagy, renal cell carcinoma, and metabolic pathways. Simultaneously, the co-expressed hub genes were analyzed to construct the mRNA-miRNA interaction network and important miRNAs such as hsa-mir-155-5p, hsa-mir-1-3p, and hsa-mir-124-3p were obtained. Finally, 75 drugs targeting 54 important circRNAs and FRGs were predicted. This study identified the Hub FRGs and transcriptomic molecules from FSGS in renal tubules, thus providing novel diagnostic and therapeutic targets for FSGS.

Abstract Objective To analyze the clinical phenotype and genetic characteristics of a female proband carrying a novel mutation in the DMD gene with non-random X-chromosome inactivation in a large pedigree with pseudohypertrophic muscular dystrophy. Methods Clinical information of the female proband, her monozygotic twin sister, and other family members were collected. Potential pathogenic variants were detected with Multiplex Ligation-dependent Probe Amplification (MLPA) and whole-exome sequencing (WES). Methylation-sensitive restriction enzyme (HhaI) was employed for X-chromosome inactivation analysis. Results The proband was a female over 5 years old, displayed clinical manifestations such as elevated creatine kinase (CK) levels and mild calf muscle hypertrophy. Her monozygotic twin sister exhibited normal CK levels and motor ability. Her uncle and cousin had a history of DMD. WES revealed that the proband carried a novel variant in the DMD (OMIM: 300,377) gene: NM_004006.3: c.3051_3053dup; NP_003997.2: p.Tyr1018*. In this pedigree, five out of six female members were carriers of this variant, while the cousin and uncle were hemizygous for this variant. X-chromosome inactivation analysis suggested non-random inactivation in the proband. Conclusion The c.3051_3053dup (p.Tyr1018*) variant in the DMD gene is considered to be the pathogenic variant significantly associated with the clinical phenotype of the proband, her cousin, and her uncle within this family. Integrating genetic testing with clinical phenotype assessment can be a valuable tool for physicians in the diagnosis of progressive muscular dystrophies, such as Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD).

Abstract Background Brucellosis is a severe zoonotic disease that is often overlooked, particularly in impoverished countries. Timely identification of focal complications in brucellosis is crucial for improving treatment outcomes. However, there is currently a lack of established indicators or biomarkers for diagnosing these complications. Therefore, this study aimed to investigate potential warning signs of focal complications in human brucellosis, with the goal of providing practical parameters for clinicians to aid in the diagnosis and management of patients. Methods A multi-center cross-sectional study was conducted in China from December 2019 to August 2021. The study aimed to investigate the clinical characteristics and complications of patients with brucellosis using a questionnaire survey and medical record system. The presence of warning signs for complications was assessed using univariate and multivariate logistic regression models. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used for variable screening and model evaluation. Results A total of 880 participants diagnosed with human brucellosis were enrolled. The median age of the patients was 50 years [interquartile range (IQR): 41.5–58.0], and 54.8% had complications. The most common organ system affected by complications was the osteoarticular system (43.1%), with peripheral arthritis (30.0%), spondylitis (16.6%), paravertebral abscess (5.0%), and sacroiliitis (2.7%) being the most prevalent. Complications in other organ systems included the genitourinary system (4.7%), respiratory system (4.7%), and hematologic system (4.6%). Several factors were found to be associated with focal brucellosis. These factors included a long delay in diagnosis [odds ratio (OR) = 3.963, 95% confidence interval (CI) 1.906–8.238 for > 90 days], the presence of underlying disease (OR = 1.675, 95% CI 1.176–2.384), arthralgia (OR = 3.197, 95% CI 1.986–5.148), eye bulging pain (OR = 3.482, 95% CI 1.349–8.988), C-reactive protein (CRP) > 10 mg/L (OR = 1.910, 95% CI 1.310–2.784) and erythrocyte sedimentation rate (ESR) elevation (OR = 1.663, 95% CI 1.145–2.415). The optimal cutoff value in ROC analysis was > 5.4 mg/L for CRP (sensitivity 73.4% and specificity 51.9%) and > 25 mm/h for ESR (sensitivity 47.9% and specificity 71.1%). Conclusions More than 50% of patients with brucellosis experienced complications. Factors such as diagnostic delay, underlying disease, arthralgia, eye pain, and elevated levels of CRP and ESR were identified as significant markers for the development of complications. Therefore, patients presenting with these conditions should be closely monitored for potential complications, regardless of their culture results and standard tube agglutination test titers.

BackgroundAngiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes.MethodsWe performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software.ResultsA total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: −2.85 mmHg), clinic SBP (MD: −3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: −1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: −3.59 mmHg), 24-h ABPM mean DBP (MD: −2.62 mmHg), clinic SBP (MD: −4.42 mmHg), clinic DBP (MD: −3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in the 40-mg AZL-M group. Analysis of patients with diabetes revealed that AZL-M can provide superior management, while safety and tolerability were similar to those of control therapy.ConclusionsAZL-M appears to reduce BP to a greater extent than dose-control therapy and does not increase the risk of adverse events in patients with hypertension and diabetes compared with placebo.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=464284, identifier PROSPERO CRD42023464284.

Abstract Background This prospective real‐world study aimed to assess the efficacy and safety of eribulin in the clinical practice against advanced breast cancer (ABC) in China. Patients and Methods In this study, eligible patients with inoperable locally advanced or metastatic breast cancer who had experienced prior neo−/adjuvant or failed the palliative treatment with anthracycline/taxanes were included. Eribulin (1.4 mg/m2) was infused intravenously on Day 1 and Day 8 every 3 weeks until disease progression or intolerable toxicity occurred. The progression‐free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety of the treatment were assessed. Results One hundred and thirty‐four patients were enrolled. The median PFS (mPFS) was 4.3 months (95% CI: 0.3–15.4). The ORR and DCR was 32.1% and 79.1%, respectively. The mPFS of patients who received eribulin as first‐ or second‐line treatment was significantly better than those who received eribulin as ≥3‐line treatment (6.9 months [95% CI: 3.2–8.8] vs. 4.0 months [95% CI: 3.4–4.6], p = 0.006). The mPFS of patients with triple‐negative, HER2‐positive, and HER2(−)/HR(+) was 3.4 (95% CI: 2.7–4.1), 6.2 (95% CI: 2.3–10.1) and 5.0 months (95% CI: 4.1–5.9), respectively. HER2(+) patients had significantly longer PFS than TNBC patients (p = 0.022). Patients received combination therapy had a significantly longer mPFS than those who received eribulin monotherapy (5.0 months [95% CI 3.6–6.3] vs. 4.0 months [95% CI: 3.3–4.7] [p = 0.016]). Multivariate analysis revealed that MBC patients with a molecular typing of non‐TNBC receiving eribulin as ≤2‐line therapy and combination therapy had a low risk of disease progression. Neutropenia (33.58%), leukopenia (11.94%), and thrombocytopenia (4.48%) were the most common treatment‐related adverse events. Conclusion Eribulin demonstrated effective clinical activity and a favorable tolerability profile in Chinese patients with ABC in the real‐world. The efficacy and safety profile were consistent with those reported in previous randomized phase 3 trials.

Objectives The study aimed to understand the composition, epidemiological characteristics and disease burden of chronic non-communicable diseases and to evaluate the association between sociodemographic factors and chronic non-communicable diseases.Design A cross-sectional study.Setting and participants Medical records of 196 761 residents were collected from Dongfang disease surveillance system from January to December 2021.Primary outcome Prevalence and disability burden were recorded. Logistic regression was used to investigate the relationship between sociodemography factors and diseases.Results Cardiovascular diseases, chronic lower respiratory diseases and other upper respiratory tract diseases were the main chronic non-communicable diseases. In multivariable analysis, men were associated with increased risk of cardiovascular diseases (OR=1.210, 95% CI 1.162 to 1.261) and chronic lower respiratory diseases (OR=1.128, 95% CI 1.079 to 1.180). Older age was associated with increased risk of cardiovascular diseases (OR=83.952, 95% CI 58.954 to 119.550), whereas was associated with decreased risk of chronic lower respiratory diseases (OR=0.442, 95% CI 0.415 to 0.471) and other upper respiratory tract diseases (OR=0.450, 95% CI 0.411 to 0.493). The unemployed and poor household were associated with decreased risk of cardiovascular diseases (OR=0.463, 95% CI 0.412 to 0.521 and OR=0.390, 95% CI 0.342 to 0.444, respectively), whereas were associated with increased risk of chronic lower respiratory diseases (OR=12.219, 95% CI 6.343 to 23.539 and OR=10.954, 95% CI 5.666 to 21.177, respectively) and other upper respiratory tract diseases (OR=2.246, 95% CI 1.719 to 2.936 and OR=3.035, 95% CI 2.308 to 3.991, respectively). Gender and age moderated the association between personnel category and major diseases.Conclusions The spectrum and epidemiological characteristics of chronic diseases observed in Dongfang is good evidence for developing prevention guides and health policies for region.

Background & Aims: Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration. Methods: Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration. Results: We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy. Conclusions: These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.

Although drilling open holes in fibre metal laminates reduces weight, it brings potential crack initiation sites. This paper investigates the effect of laser shock peening (LSP) on fatigue performance of open-hole titanium-based carbon-fibre/epoxy laminates (Ti-CF FMLs). A method based on multi-step simulation was proposed for the reconstruction of LSP induced residual stress field in open-hole Ti-CF FMLs. The results show that the fatigue initiation life of open-hole Ti-CF FMLs is improved by 22.1 %–81.0 % after LSP, depending on the structure of FMLs and the applied fatigue load. The improved fatigue crack initiation life attributes to compressive residual stress generated throughout the entire depth of the hole wall in outer titanium layer in Ti-CF FMLs after LSP. However, LSP leads to the formation of tensile residual stress far from the hole edge, resulting in accelerated propagation of fatigue crack. The fatigue initiation lives of open-hole Ti-CF FMLs before and after LSP were calculated by finite element simulation and theoretical method, showing good consistency.

Ralstonia solanacearum causes a lethal bacterial wilt disease in many crops, leading to huge losses in crop production every year. Understanding of plant–R. solanacearum interactions will aid to develop efficient strategies to control the disease. As a soilborne pathogen, R. solanacearum naturally infects plants via roots. A huge limitation in studying plant–R. solanacearum interactions is the large variation of R. solanacearum infection assay due to the variable soil conditions and uneven inoculum exposure. Here, we developed a robust and reliable Petri-dish inoculation method which allows consistent and stable infection in young plant seedlings. This method is easy to use, takes about only 10 days from seed germination to the completion of inoculation assay, and requires less inoculum of bacteria as well as growth chamber space. We proved the efficacy of the seedling Petri-dish inoculation method by analyzing plant defense primed by molecular patterns, resistance of defense-related plant mutants, and virulence of R. solanacearum mutants. Furthermore, we demonstrated that the seedling Petri-dish inoculation method can be applied to other host plants such as tobacco and has great potential for high-throughput screening of resistant plant germplasms to bacterial wilt in the future.

Abstract Background Breast cancer is the leading cause of cancer death for women worldwide. Most of the breast cancer death are due to disease recurrence and metastasis. Increasingly accumulating evidence indicates that mitochondria play key roles in cancer progression and metastasis. Our recent study revealed that transmembrane protein PRRG4 promotes the metastasis of breast cancer. However, it is not clear whether PRRG4 can affect the migration and invasion of breast cancer cells through regulating mitochondria function. Methods RNA-seq analyses were performed on breast cancer cells expressing control and PRRG4 shRNAs. Quantitative PCR analysis and measurements of mitochondrial ATP content and oxygen consumption were carried out to explore the roles of PRRG4 in regulating mitochondrial function. Luciferase reporter plasmids containing different lengths of promoter fragments were constructed. Luciferase activities in breast cancer cells transiently transfected with these reporter plasmids were analyzed to examine the effects of PRRG4 overexpression on promoter activity. Transwell assays were performed to determine the effects of PRRG4-regulated pathway on migratory behaviors of breast cancer cells. Results Analysis of the RNA-seq data revealed that PRRG4 knockdown decreased the transcript levels of all the mitochondrial protein-encoding genes. Subsequently, studies with PRRG4 knockdown and overexpression showed that PRRG4 expression increased mitochondrial DNA (mtDNA) content. Mechanistically, PRRG4 via Src activated STAT3 in breast cancer cells. Activated STAT3 in turn promoted the transcription of mtDNA polymerase POLG through a STAT3 DNA binding site present in the POLG promoter region, and increased mtDNA content as well as mitochondrial ATP production and oxygen consumption. In addition, PRRG4-mediated activation of STAT3 also enhanced filopodia formation, migration, and invasion of breast cancer cells. Moreover, PRRG4 elevated migratory behaviors and mitochondrial function of breast cancer cells through POLG. Conclusion Our results indicate that PRRG4 via the Src-STAT3-POLG axis enhances mitochondrial function and promotes migratory behaviors of breast cancer cells.

The positive effects of multimodal instruction have been widely assumed, but few studies have looked into the impact of multimodal tutorials within the context of an Intensive English Program (IEP). Hence, to address the research gap, the aim of this study was to investigate the impact of multimodality and tutoring assistance within an IEP on the language proficiency of EFL learners. The IEP program consisted of two phases, featuring three forms of tutoring: non-tutoring, multimodality tutoring, and multimodality mentor-tutoring. The research questions were answered using both experimental and survey methods. The quasi-experimental study was conducted (N = 467) with two fixed factors, that is, Type of Tutoring and Phase. A questionnaire was further distributed to measure students' perceptions of learning, including learning effort (LE), perception of TA scaffolding (TASCAF), and willingness to continue learning (WTL). The results of two-way ANCOVA indicated a significant effect of Type of Tutoring (p < 0.001), and interaction between Type of Tutoring and Phase (p < 0.05). Structural equation modeling testing the model fitness (i.e., LE contributes significantly both directly and indirectly through TASCAF) indicated an acceptable goodness of fit (CFI = 0.952, SRMR = 0.036, and RMSEA = 0.80), supporting the significant contribution of Type of Tutoring to students' English learning. In summary, the multimodal tutorial environment reinforced the contemporary tenet that language learning is fundamentally socially mediated. This aspect underscores the creation of a multimodal learning context with an optimal interplay among mentors, tutors, instructors, and students.

Abstract Aim This research aims to offer a reference point for relevant departments to enhance the allocation of ageing resources and formulate policies accordingly. Design This study is designed as empirical quantitative research. Methods Data from the National Bureau of Statistics and the Ministry of Civil Affairs regarding older adults (aged≥60) from 2000 to 2022 and nursing beds from 1978 to 2022 were analysed. The differential autoregressive integrated moving averages model and Monte Carlo simulation were used to predict the growth of nursing beds per 1000 older people in China for the Years 2023–2025. Results It is projected that from 2023 to 2025, China will experience a further increase in its ageing population, with an average annual growth rate of 3.1%. By 2025, the number of older people in China is expected to surpass 300 million. Additionally, there will be a rise in the number of nursing beds, with an average annual growth rate of 1.9%, leading to a total of 8.79 million nursing beds by 2025. However, due to the rapid growth of the older population, there will be a slight decline in the number of nursing beds per 1000 older people in China, with an average annual growth rate of −1.00%.

ObjectiveThis retrospective study aimed to investigate the clinical features of optic neuritis associated with COVID-19 (COVID-19 ON), comparing them with neuromyelitis optica-associated optic neuritis (NMO-ON), myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON), and antibody-negative optic neuritis (antibody-negative ON).MethodsData from 117 patients (145 eyes) with optic neuritis at the Shantou International Eye Center (March 2020–June 2023) were categorized into four groups based on etiology: Group 1 (neuromyelitis optica-related optic neuritis, NMO-ON), Group 2 (myelin oligodendrocyte glycoprotein optic neuritis, MOG-ON), Group 3 (antibody-negative optic neuritis, antibody-negative ON), and Group 4 (optic neuritis associated with COVID-19, COVID-19 ON). Characteristics of T2 and enhancement in orbital magnetic resonance imaging (MRI) were assessed. Best-corrected visual acuity (BCVA) was compared before treatment, at a short-term follow-up (14 days), and at the last follow-up after treatment.ResultsThe COVID-19-associated optic neuritis (COVID-19 ON) group exhibited 100% bilateral involvement, significantly surpassing other groups (P < 0.001). Optic disk edema was observed in 100% of COVID-19 ON cases, markedly differing from neuromyelitis optica-related optic neuritis (NMO-ON) (P = 0.023). Orbital magnetic resonance imaging (MRI) revealed distinctive long-segment lesions without intracranial involvement in T1-enhanced sequences for the COVID-19 ON group compared to the other three groups (P < 0.001). Discrepancies in optic nerve sheath involvement were noted between the COVID-19 ON group and both NMO-ON and antibody-negative optic neuritis (antibody-negative ON) groups (P = 0.028). Before treatment, no significant difference in best-corrected visual acuity (BCVA) existed between the COVID-19 ON group and other groups. At the 14-day follow-up, BCVA in the COVID-19 ON group outperformed the NMO-ON (P < 0.001) and antibody-negative ON (P = 0.028) groups, with no significant difference observed compared to the myelin oligodendrocyte glycoprotein optic neuritis (MOG-ON) group. At the last follow-up after treatment, BCVA in the COVID-19 ON group significantly differed from the NMO-ON group (P < 0.001).ConclusionOptic neuritis associated with COVID-19 (COVID-19 ON) predominantly presents with bilateral onset and optic disk edema. Orbital magnetic resonance imaging (MRI) demonstrates that COVID-19 ON presents as long-segment enhancement without the involvement of the intracranial segment of the optic nerve in T1-enhanced images. Glucocorticoid therapy showed positive outcomes.

Background: Bibliometrics can trace general research trends in a particular field. Mucopolysaccharidoses (MPS), as a group of rare genetic diseases, seriously affect the quality of life of patients and their families. Scholars have devoted themselves to studying MPS’s pathogenesis and treatment modalities and have published many papers. Therefore, we conducted a bibliometric and visual study of the top 100 most highly cited articles to provide researchers with an indication of the current state of research and potential directions in the field.Methods: The Web of Science Core Collection was searched for articles on MPS from 1 January 1900, to 8 November 2023, and the top 100 most cited articles were screened. The title, year of publication, institution, country, and first author of the articles were extracted and statistically analyzed using Microsoft Excel 2007. Keyword co-occurrence and collaborative networks were analyzed using VOSviewer 1.6.16.Results: A total of 9,273 articles were retrieved, and the top 100 most cited articles were filtered out. The articles were cited 18,790 times, with an annual average of 188 citations (122–507). Forty-two journals published these articles, with Molecular Genetics and Metabolism and Proceedings of the National Academy of Sciences of the United States being the most published journal (N = 8), followed by Pediatrics (N = 7), Blood (N = 6). The United States (N = 68), the UK (N = 25), and Germany (N = 20) were the top contributing countries. The Royal Manchester Children’s Hospital (N = 20) and the University of North Carolina (N = 18) were the most contributing institutions. Muenzer J was the most prolific author (N = 14).Conclusion: We conducted a bibliometric and visual analysis of the top 100 cited articles in MPS. This study identifies the most influential articles currently available in the field of MPS, which provides a good basis for a better understanding of the disease and informs future research directions.

Tyrosine kinase inhibitors (TKIs) have emerged as the first-line small molecule drugs in many cancer therapies, exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways. However, there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites, which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments, alongside other potential side effects or adverse reactions. Therefore, an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods, clinical pharmacokinetics, and therapeutic drug monitoring of different TKIs. This paper provides a comprehensive overview of the advancements in pretreatment methods, such as protein precipitation (PPT), liquid-liquid extraction (LLE), solid-phase extraction (SPE), micro-SPE (μ-SPE), magnetic SPE (MSPE), and vortex-assisted dispersive SPE (VA-DSPE) achieved since 2017. It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) methods, capillary electrophoresis (CE), gas chromatography (GC), supercritical fluid chromatography (SFC) procedures, surface plasmon resonance (SPR) assays as well as novel nanoprobes-based biosensing techniques. In addition, a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.

Background: There are limited population studies on the neurodevelopmental effects of bisphenol F (BPF), a substitute for bisphenol A. Furthermore, the role of placental estradiol as a potential mediator linking these two factors remains unclear. Objective: To examine the association between maternal prenatal BPF exposure and infant neurodevelopment in a prospective cohort study and to explore the mediating effects of placental estradiol between BPF exposure and neurodevelopment in a nested case-control study. Methods: The prospective cohort study included 1077 mother-neonate pairs from the Wuhu city cohort study in China. Maternal BPF was determined using the liquid/liquid extraction and Ultra-performance liquid chromatography tandem mass spectrometry method. Children's neurodevelopment was assessed at ages 3, 6, and 12 months using Ages and Stages Questionnaires. The nested case-control study included 150 neurodevelopmental delay cases and 150 healthy controls. Placental estradiol levels were measured using enzyme-linked immunosorbent assay kits. Generalized estimating equation models and robust Poisson regression models were used to examine the associations between BPF exposure and children's neurodevelopment. In the nested case-control study, causal mediation analysis was conducted to assess the role of placental estradiol as a mediator in multivariate models. Results: In the prospective cohort study, the pregnancy-average BPF concentration was positively associated with developmental delays in gross-motor, fine-motor, and problem-solving ( ORtotal ASQ: 1.14(1.05, 1.25), ORgross-motor: 1.22(1.10, 1.36), ORfine-motor: 1.19(1.07, 1.31), ORproblem-solving: 1.11(1.01, 1.23)). After sex-stratified analyses, pregnancy-average BPF concentration was associated with an increased risk of neurodevelopmental delays in the gross-motor (ORgross-motor:1.30(1.12, 1.51)) and fine-motor (ORfine-motor: 1.22(1.06, 1.40)) domains in boys. In the nested case-control study, placental estradiol mediated 16.6% (95%CI: 4.4%, 35.0%) of the effects of prenatal BPF exposure on developmental delay. Conclusions: Our study supports an inverse relationship between prenatal BPF exposure and child neurodevelopment in infancy, particularly in boys. Decreased placental estradiol may be an underlying biological pathway linking prenatal BPF exposure to neurodevelopmental delay in offspring.

Abstract Objective This study explored using an improved ultrasound (US) for quantitative evaluation of the degree of pelvic organ prolapse(POP). Design A transluminal probe was used to standardize ultrasound imaging of pelvic floor organ displacements. A US reference line was fixed between the lower edge of the pubic symphysis and the central axis of the pubic symphysis at a 30°counterclockwise angle. Method Points Aa, Ba, C and Bp on pelvic organ prolapse quantification (POP-Q) were then compared with the points on pelvic floor ultrasound (PFUS). Results One hundred thirteen patients were included in the analysis of the standard US plane. Correlations were good in the anterior and middle compartments (PBN:Aa, ICC = 0.922; PBB:Ba, ICC = 0.923; and PC:C, ICC = 0.925), and Bland-Altman statistical maps corresponding to the average difference around the 30°horizontal line were close to 0. Correlations were poor in the posterior compartment (PRA:Bp, ICC = 0.444). However, eight (7.1%) cases of intestinal hernia and 21 (18.6%) cases of rectocele were diagnosed. Conclusions Introital PFUS using an intracavitary probe, which is gently placed at the introitus of the urethra and the vagina, may be accurately used to evaluate organ displacement. The application of a 30°horizontal line may improve the repeatability of the US diagnosis of POP.

Synthesizing hyperspectral images (HSI) from an ordinary camera has been accomplished recently. However, such computation models require detailed properties of the target camera, which can only be measured in a professional lab. This prerequisite prevents the synthesizing model from being installed on arbitrary cameras for end-users. This study offers a calibration-free method for transforming any camera into an HSI camera. Our solution requires no controllable light sources and spectrometers. Any consumer installing the program should produce high-quality HSI without the assistance of optical laboratories. Our approach facilitates a cycle-generative adversarial network (cycle-GAN) and sparse assimilation method to render the illumination-dependent spectral response function (SRF) of the underlying camera at the first part of the setup stage. The current illuminating function (CIF) must be identified for each image and decoupled from the underlying model. The HSI model is then integrated with the static SRF and dynamic CIF in the second part of the stage. The estimated SRFs and CIFs have been double-checked with the results by the standard laboratory method. The reconstructed HSIs have errors under 3% in the root mean square.