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Findings for greenspace's impacts on birth outcomes are largely dependent on vegetation indexes. Examinations are needed for various greenspace indicators given varying pathways for fetal development. This prospective cohort study assessed the impacts of prenatal greenspace exposure on preterm birth (PTB), term low birthweight (TLBW), birthweight, and estimated fetal weight (EFW) for pregnant women in the New York City area, 2016-2023 (n=2765). Longitudinal greenspace exposure was measured for residential histories during pregnancy using the Enhanced Vegetation Index (EVI) for 1000m buffers and four park metrics, namely, the total number, sum of area, and the accessibility of parks within residential buffers (500 m) and the distance to the closest park. Multivariable regression models were used to estimate the associations for quartiles of exposure (with the first quartile [Q1] as reference). Greenspace exposure was not associated with TLBW, birthweight, or EFW. Odds ratios of PTB for the Q2, Q3, and Q4 EVI exposure groups compared to the Q1 group were 0.65 (95% CI: 0.43-0.98), 0.51 (0.32-0.80), and 0.56 (0.35-0.90), respectively. PTB risks decreased in higher exposure groups (Q2-Q4) of the total park number. Results indicate the benefits of prenatal greenspace exposure for fetal maturity and neonatal outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The methods available for treating metastatic Ewing sarcoma (ES) are inadequate; thus, innovative therapeutic approaches need to be developed. However, the lack of clinically relevant ES models has hindered the discovery of drugs for this disease. In this study, we established and characterized a patient-derived xenograft (PDX) cell line model, which was constructed using tumor tissue from a patient with metastatic extraskeletal ES. The cells were found to recapitulate the morphological and histopathological features of the patient tumor and were designated as ES-ZSS-1. The cells harbor the characteristic EWSR1-FLI1 infusion and underwent successive passages in vitro. By performing gene expression profiling, we found that the mutation in STAG2 was the most frequent. An increase in Twist1 and epithelial-to-mesenchymal transition (EMT) was recorded. These genetic features might be relevant to metastasis and resistance to chemotherapy. To summarize, the novel patient-derived ES cell line we developed closely mimics the phenotype and genotype of patient tumors, making it a reliable tool for research on metastatic ES., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Effective hydrogen evolution reaction (HER) under high current density and enhanced hydrogen oxidation reaction (HOR) over a wide potential range remain challenges for Ru-based electrocatalysts because its strong affinity to the adsorbed hydroxyl (OH ad ) inhibits the supply of the adsorbed hydrogen (Had). Herein, the coexisting RuOTi and Ru-Ti bonds are constructed by taking TiO 2 crystal confined flat-Ru clusters (F-Ru@TiO 2 ) to cope with above-mentioned obstacles. The different electronegativity (χ Ti = 1.54 < χ Ru = 2.20 < χ O = 3.44) can endow Ti sites in RuOTi bonds with more positive charge and stabilize Ru atoms of RuTi bonds with the low-valence. The strength of Ru-OH ad is then weakened by the oxophilicity of positively charged Ti atom in Ru-O-Ti bonds and the stronger Ti-OH ad bond could release active Ru sites, especially for low-valence Ru in RuTi bonds, to serve as exclusive Had sites. As expected, F-Ru@TiO 2 shows a low HER overpotential of 74 mV at 1000 mA cm -2 and an ultrahigh mass activity of 3155 A g Ru -1 for HOR. More importantly, F-Ru@TiO 2 can tolerate the HER current density of 1000 mA cm -2 for 100 h and the high anodic potential for HOR up to 0.5 V versus RHE., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The knee adduction moment(KAM) of both lower limbs in patients with unilateral knee osteoarthritis(KOA) exhibits asymmetry during walking, but the factors influencing this asymmetry remain unclear. This study aimed to explore the influencing factors of KAM asymmetry in patients with unilateral KOA., Methods: A total of 148 patients with unilateral medial compartment KOA were selected for this retrospective study, and general data such as gender, age, and duration of disease were collected. The hip-knee-ankle (HKA) angle, degree of pain, and knee-extension muscle strength on the affected side were assessed through radiographic outcomes, the visual analog scale(VAS), and the Biodex isokinetic system. The peak KAM of both lower limbs was analyzed using a BTS motion-capture system and force platform. The asymmetry index(ASI) of KAM was calculated, and the patients were further categorized into the KAM symmetry group(ASI value ≤ 10%) and the KAM asymmetry group(ASI value>10%).Binary logistic regression analysis was employed to analyze the factors influencing the asymmetry of KAM., Results: 90 patients were categorized into the KAM asymmetry group, representing 60.8% of the cohort. A significant difference in the ASI value of KAM was observed between the two groups. Correlation analysis identified nine factors, including sex, age, and BMI, that were positively correlated with the ASI value of KAM. In contrast, knee-extension muscle strength and per-capita monthly household income were negatively correlated with the ASI value of KAM. Regression analysis revealed that being female(OR = 1.752), older age(OR = 2.472), increased BMI(OR = 1.535), larger varus angle(OR = 3.965), higher VAS score(OR = 2.617), Kellgren-Lawrence(K-L) grade IV(OR = 4.474), history of knee joint trauma(OR = 5.684), and living in a rural location(OR = 1.554) increased the risk of KAM asymmetry. Conversely, increased knee-extension muscle strength(OR = 0.758) and a per-capita monthly household income of 3000 ~ 6000 yuan(OR = 0.814) decreased the risk of KAM asymmetry., Conclusion: Female gender, older age, increased BMI, larger varus angle, higher VAS score, K-L grade IV, history of knee joint trauma, and living in a rural location are identified as risk factors for KAM asymmetry. Conversely, increased knee-extension muscle strength and a per-capita monthly household income of 3000 ~ 6000 yuan serve as protective factors against this asymmetry., (© 2024. The Author(s).)

Purpose: To examine the association between cumulative exposure to neighborhood walkability (NW) and diabetes risk., Methods: A total of 11,037 women free of diabetes at enrollment were included. We constructed a 4-item NW index at baseline, and a 2-item average annual NW across years of follow-up that captured both changes in neighborhood features and residential moves. We used multivariable Cox PH regression models with robust variance to estimate the hazard ratios (HRs) of diabetes by NW scores., Results: Compared with women living in areas with lowest NW (Q1), those living in areas with highest NW (Q4) had 33 % (26 %-39 %) reduced risk of incident diabetes, using baseline NW, and 25 % (95 % CI 11 %-36 %), using average annual NW. Analysis using time-varying exposure showed that diabetes risks decreased by 13 % (10 %-16 %) per -standard deviation increase in NW. The associations remained similar when using inverse probability of attrition weights and/or competing risk models to account for the effect of censoring due to death or non-response. The associations of average annual NW with incident diabetes were stronger in postmenopausal women as compared to premenopausal women., Conclusion: Long-term residence in more walkable neighborhoods may be protective against diabetes in women, especially postmenopausal women., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Yu Chen reports a relationship with New York University Grossman School of Medicine that includes: employment. If there are other authors, they 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 Inc.)

Previous studies have provided evidence for associations between glyphosate and aminomethylphosphonic acid (AMPA) exposure and adverse birth outcomes. However, few pregnancy cohort studies have investigated dietary and other determinants of glyphosate and AMPA exposure. We aimed to identify dietary and sociodemographic factors that predict glyphosate and AMPA exposure in a contemporary, urban pregnancy cohort in the US. The study included 725 pregnant participants from the New York University Children's Health and Environment Study (NYU CHES) in New York City. Urinary concentrations of glyphosate and AMPA, determined by high-performance liquid chromatography and tandem mass spectrometry, were analyzed in urine collected from NYU CHES participants across three prenatal time points. The Diet Health Questionnaire II was completed to capture dietary intake during the prenatal period. Descriptive statistics and bivariate linear models were used to assess determinants of urinary glyphosate and AMPA concentrations. Median urinary glyphosate and AMPA levels were 0.36 ng/mL and 0.37 ng/mL, respectively. Lower glyphosate levels were associated with younger age, obesity, public insurance, being single, and lower educational attainment. Nuts, seeds and whole grain intake was associated with increased urinary glyphosate concentrations. Urinary glyphosate concentrations were lower in summer than in winter. The study findings highlight widespread exposure to glyphosate and AMPA in this pregnancy cohort, with nuts/seeds and whole grains identified as possible dietary sources of exposure. High detection rates in the study population necessitate further research on dietary exposure patterns and perinatal outcomes to inform targeted interventions and reduce exposure in vulnerable populations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Whitney Cowell reports financial support was provided by National Institute of Environmental Health Sciences. Leonardo Trasande reports financial support was provided by National Institute of Health. If there are other authors, they 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 Elsevier Ltd. All rights reserved.)

In studies with time-to-event outcomes, multiple, inter-correlated, and time-varying covariates are commonly observed. It is of great interest to model their joint effects by allowing a flexible functional form and to delineate their relative contributions to survival risk. A class of semiparametric transformation (ST) models offers flexible specifications of the intensity function and can be a general framework to accommodate nonlinear covariate effects. In this paper, we propose a partial-linear single-index (PLSI) transformation model that reduces the dimensionality of multiple covariates into a single index and provides interpretable estimates of the covariate effects. We develop an iterative algorithm using the regression spline technique to model the nonparametric single-index function for possibly nonlinear joint effects, followed by nonparametric maximum likelihood estimation. We also propose a nonparametric testing procedure to formally examine the linearity of covariate effects. We conduct Monte Carlo simulation studies to compare the PLSI transformation model with the standard ST model and apply it to NYU Langone Health de-identified electronic health record data on COVID-19 hospitalized patients' mortality and a Veteran's Administration lung cancer trial., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Colorectal cancer (CRC) with BRAF V600E mutation presents a formidable scientific and clinical challenge due to its aggressive nature and poor response to standard therapeutic approaches. BRAF V600E mutation-induced conspicuous activation of the MAPK pathway contributes to the relentless tumor progression. Nevertheless, the efficacy of multi-targeted MAPK pathway inhibition remains suboptimal in clinical practice. Patients with high microsatellite instability (MSI-H) have shown favorable results with immune checkpoint inhibitors (ICIs). The combination of the MAPK pathway inhibition with ICIs has recently emerged as a promising regimen to improve clinical outcomes in the microsatellite stable (MSS) subgroup of BRAF V600E-mutant metastatic CRC patients. In this review, we elucidate the unique tumor biology of BRAF V600E-mutant CRC, with a particular focus on the immune features underlying the rationale for ICI treatments in the MSI-H and MSS subpopulations, then highlight the trends in clinical trials of the ICI therapy for BRAF V600E-mutant metastatic CRC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

It is important to understand the impact of consumer chemical exposure and fecundity, a couple's measure of probability of successful conception, given approximately 15% of couples experience infertility. Prior research has generally found null associations between bisphenol and phthalate exposure and fecundability, measured via time to pregnancy (TTP). However, this research has not been updated with current chemical exposures and have often lacked diversity in their study populations. We evaluated the associations between common bisphenol and phthalate chemical exposure groups and TTP as well as subfecundity (TTP>12 months) in the New York University Children's Health Study, a diverse pregnancy cohort from 2016 onward. Using first-trimester spot-urine samples to measure chemical exposure and self-reported TTP from first-trimester questionnaires, we observed a significant adverse association between total bisphenol exposure and certain phthalate groups on TTP and odds of subfecundity. Furthermore, in a mixtures analysis to explore the joint effects of the chemical groups on the outcomes, we found evidence of a potential interaction between total bisphenol exposure and low-molecular weight phthalates on TTP. Future research should continue to update our knowledge regarding the complex and potentially interacting effects of these chemicals on reproductive health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mia Charifson reports financial support was provided by National Science Foundation. Mengling Liu reports financial support was provided by National Institute of Environmental Health Sciences. Eunsil Seok reports financial support was provided by National Institute of Environmental Health Sciences. Yuyan Wang reports financial support was provided by National Institute of Environmental Health Sciences. Leonardo Trasande reports financial support was provided by National Institutes of HealthOffice of the Director. Linda Kahn reports financial support was provided by National Institute of Environmental Health Sciences. If there are other authors, they 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 Elsevier Ltd. All rights reserved.)

The optimization of the adsorption of oxygen-containing intermediates on platinum (Pt) sites of Pt-based electrocatalysts is crucial for the oxygen reduction reaction process. Currently, a large amount of researches mainly focus on modifying the bulk structure of the electrocatalysts, however, the vital role of solvent effect on the phase interfaces is often overlooked. Here, we successfully developed an electrocatalyst in which the ordered PtCo alloy anchors on the cobalt (Co) single-atoms/clusters decorated support (Co 1,n NC) and its surface is further optimized using hydrophobic ionic liquid (IL). Experimental studies and theoretical calculations indicate that compressive stress on Pt lattice contributed by intrinsic structure and the local hydrophobicity caused by IL on the surface can suppress the stabilization of *OH on Pt. This synergistic effect affords outstanding catalytic performance, exhibiting a half-wave potential (E 1/2 ) of 0.916 V vs. RHE and a mass activity (MA) of 1350.3 mA mg Pt -1 in 0.1 mol/L perchloric acid (0.1 M HClO 4 ) electrolyte, much better than the commercial Pt/C (0.849 V vs. RHE and 145.5 mA mg Pt -1 for E 1/2 and MA, respectively). Moreover, the E 1/2 of IL-PtCo/Co 1,n NC only lost 5 mV after 10,000 cyclic voltammetry (CV) cycles due to a strong and synergistic contact of the intermetallic PtCo alloy with the Co 1,n NC support and IL. This research provides an effective method for designing efficient electrocatalysts by combining intrinsic structure and surface modification., 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 Elsevier Inc. All rights reserved.)

Background: Treatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients., Methods: Cancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed., Results: Fifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2-186) days and the median duration of tofacitinib treatment was 52.5 (range, 3-277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P < 0.01). Tofacitinib was well-tolerated with 4 patients (7.5%) developing infectious events. From the ICI initiation, the overall median OS was 16.1 (95% CI 7.8-26.9) months., Conclusion: Tofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroids or experienced relapse during steroid tapering. Moreover, and most importantly, tofacitinib exhibited a favorable safety profile in cancer patients developing irAEs in terms of both toxicity and anti-tumor activity. Future prospective studies are warranted., (© 2024. The Author(s).)

Background: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms., Methods: Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life., Discussion: Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care., Trial Registration: Name of Primary Registry: "Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)". Trial Identifying Number: NCT05216133 . Date of Registration: January 31, 2022., (© 2024. The Author(s).)

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at three time points. Fetal biometrics were obtained from ultrasounds in the second (n=773) and third (n=535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z-scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (-0.15 SD; 95% CI: -0.29, -0.01), head circumference (-0.11 SD; CI: -0.22, 0.01), biparietal diameter (-0.14 SD; CI: -0.27, -0.01), and abdominal circumference (-0.12 SD; CI: -0.26, 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (-0.14 SD; CI: -0.28, 0.00) and biparietal diameter (-0.12 SD; CI: -0.26, 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Environmental exposure-associated disease is an active area of study, especially in the context of increasing global air pollution and use of inhalants. Our group is dedicated to the study of exposure-related inflammation and downstream health effects. While many studies have focused on the impact of inhalants on respiratory sequelae, there is growing evidence of the involvement of other systems including autoimmune, endocrine, and gastrointestinal. This systematic review aims to provide a recent update that will underscore the associations between inhalation exposures and upper gastrointestinal disease in the contexts of our evolving environmental exposures. Keywords focused on inhalational exposures and gastrointestinal disease. Primary search identified n = 764 studies, of which n = 64 met eligibility criteria. In particular, there was support for existing evidence that PM increases the risk of upper gastrointestinal diseases. Smoking was also confirmed to be major risk factor. Interestingly, studies in this review have also identified waterpipe use as a significant risk factor for gastroesophageal reflux and gastric cancer. Our systematic review identified inhalational exposures as risk factors for aerodigestive disease, further supporting the association between environmental exposure and digestive disease. However, due to limitations on our review's scope, further studies must be done to better understand this interaction., Competing Interests: Competing interests The authors declare no competing interests.

Background: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations., Methods: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors., Findings: In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) μg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05)., Interpretation: We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve., Funding: This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences., Competing Interests: SMB is supported by the Royal Netherlands Academy of Arts and Sciences. JSL declares grants from Ferring Pharmaceuticals and Merck, consulting fees from Ferring Pharmaceuticals and Gedeon Richter, honoraria for lectures and support for attending meetings from Ferring Pharmaceuticals, participation to the advisory board of LOCI Trial UK, and is president of the AE PCOS society. LT is supported by the National Institute of Environmental Health Sciences. All other authors declare no conflict of interest., (© 2024 The Author(s).)

In recent years, immunotherapy, particularly PD-1 antibodies, have significantly enhanced the outcome of gastric cancer patients. Despite these advances, some patients do not respond well to treatment, highlighting the need to understand resistance mechanisms and develop predictive markers of treatment effectiveness. This study retrospectively analyzed data from 106 patients with stage IV gastric cancer who were treated with first-line immunotherapy in combination with chemotherapy. By comparing plasma cytokine levels between patients resistant and sensitive to PD-1 antibody therapy, the researchers identified elevated IL-4 expression in the resistant patients. Mechanical investigations revealed that IL-4 induces metabolic changes in macrophages that activate the PI3K/AKT/mTOR pathway. This alteration promotes ATP production, enhances glycolysis, increases lactic acid production, and upregulates FcγRIIB expression in macrophages. Ultimately, these changes lead to CD8+ T cell dysfunction and resistance to PD-1 antibody therapy in gastric cancer. These findings highlight the role of IL-4-induced macrophage polarization and metabolic reprogramming in immune resistance and verify IL-4 as potential targets for improving treatment outcomes in gastric cancer patients., (© 2024. The Author(s).)

Aims: A severe lockdown occurred in Wuhan during the COVID-19 pandemic, followed by a remission phase in the pandemic's aftermath. This study analyzed the bacterial and fungal profiles of respiratory pathogens in patients hospitalized with non-COVID-19 lower respiratory tract infections (LRTIs) during this period to determine the pathogen profile distributions in different age groups and hospital departments in Wuhan., Methods and Results: We collected reports of pathogen testing in the medical records of patients hospitalized with non-COVID-19 LRTI between 2019 and 2021. These cases were tested for bacterial and fungal pathogens using 16S and internal transcribed spacer sequencing methods on bronchoalveolar lavage fluid samples. The study included 1368 cases. The bacteria most commonly identified were Streptococcus pneumoniae (12.50%) and Mycoplasma pneumoniae (8.33%). The most commonly identified fungi were Aspergillus fumigatus (2.49%) and Pneumocystis jirovecii (1.75%). Compared to 2019, the S. pneumoniae detection rates increased significantly in 2021, and those of M. pneumoniae decreased. Streptococcus pneumoniae was detected mainly in children. The detection rates of almost all fungi were greater in the respiratory Intensive Care Unit compared to respiratory medicine. Streptococcus pneumoniae and M. pneumoniae were detected more frequently in the pediatric department., Conclusions: Before and after the COVID-19 outbreak, a change in the common pathogen spectrum was detected in patients with non-COVID-19 in Wuhan, with the greatest change occurring among children. The major pathogens varied by the patient's age and the hospital department., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Approximately 20% of colorectal cancer (CRC) patients are first diagnosed with metastatic colorectal cancer (mCRC) because they develop symptoms at an advanced stage. Despite advancements in treatment, patients with metastatic disease still experience inferior survival rates. Our objective is to investigate the association between long noncoding RNAs (lncRNAs) and prognosis and to explore their role in mCRC. In this study, we find that elevated expression of PCAT6 is independently linked to unfavourable survival outcomes in The Cancer Genome Atlas (TCGA) data, and this finding is further confirmed in CRC samples obtained from Fudan University Shanghai Cancer Center. Cell lines and xenograft mouse models are used to examine the impact of PCAT6 on tumor metastasis. Knockdown of PCAT6 is observed to impede the metastatic phenotype of CRC, as evidenced by functional assays, demonstrating the suppression of epithelial-mesenchymal transition (EMT) and stemness. Our findings show the significance of PCAT6 in mCRC and its potential use as a prognostic biomarker.

Background: The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in community-acquired pneumonia (CAP). In this study, we aim to further evaluate the etiological diagnostic value of mNGS in suspected CAP., Methods: A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy., Results: Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy., Conclusions: Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious., (© 2024. The Author(s).)

Background: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed fifirst responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal Refux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms., Methods: Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett's and Underdiagnosed Refux Noninvasively (BAD-BURN) . Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i . AHR only ii . GERD only iii . BE iv . GERD/BE and AHR overlap or v . No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life., Discussion: Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of Refux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care., Trial Registration: ClinicalTrials.gov Identifier: NCT05216133; January 18, 2022., Competing Interests: Competing interests. The authors declare that they have no competing interests. Additional Declarations: No competing interests reported.

Background: Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates during pregnancy may disrupt fetal developmental programming and influence early-life growth. We hypothesized that prenatal bisphenol and phthalate exposure was associated with alterations in adiposity through 4 years. This associations might change over time., Methods: Among 1091 mother-child pairs in a New York City birth cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at three time points in pregnancy and child weight, height, and triceps and subscapular skinfold thickness at ages 1, 2, 3, and 4 years. We used linear mixed models to assess associations of prenatal individual and grouped bisphenols and phthalates with overall and time-point-specific adiposity outcomes from birth to 4 years., Results: We observed associations of higher maternal urinary second trimester total bisphenol and bisphenol A concentrations in pregnancy and overall child weight between birth and 4 years only (Beta 0.10 (95 % confidence interval 0.04, 0.16) and 0.07 (0.02, 0.12) standard deviation score (SDS) change in weight per natural log increase in exposure), We reported an interaction of the exposures with time, and analysis showed associations of higher pregnancy-averaged mono-(2-carboxymethyl) phthalate with higher child weight at 3 years (0.14 (0.06, 0.22)), and of higher high-molecular-weight phthalate, di-2-ethylhexyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-carboxymethyl) phthalate, and mono-(2-ethylhexyl) phthalate with higher child weight at 4 years (0.16 (0.04, 0.28), 0.15 (0.03, 0.27), 0.19 (0.07, 0.31), 0.16 (0.07, 0.24), 0.11 (0.03, 0.19)). Higher pregnancy-averaged high-molecular-weight phthalate, di-2-ethylhexyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-2(ethyl-5-oxohexyl) phthalate concentrations were associated with higher child BMI at 4 years (0.20 (0.05, 0.35), 0.20 (0.05, 0.35), 0.22 (0.06, 0.37), 0.20 (0.05, 0.34), 0.20 (0.05, 0.34)). For skinfold thicknesses, we observed no associations., Discussion: This study contributes to the evidence suggesting associations of prenatal exposure to bisphenols and high-molecular-weight phthalates on childhood weight and BMI., 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.)

Gastric carcinoma (GC) is regarded as one of the deadliest cancer characterized by diversity and haste metastasis and suffers limited understanding of the spatial variation between primary and metastatic GC tumors. In this project, transcriptome analysis on 46 primary tumorous, adjacent non-tumorous, and metastatic GC tissues was performed. The results demonstrated that metastatic tumorous tissues had diminished CD8 + T cells compared to primary tumors, which is mechanistically attributed to being due to innate immunity differences represented by marked differences in macrophages between metastatic and primary tumors, particularly those expressing ApoE, where their abundance is linked to unfavorable prognoses. Examining variations in gene expression and interactions indicated possible strategies of immune evasion hindering the growth of CD8 + T cells in metastatic tumor tissues. More insights could be gained into the immune evasion mechanisms by portraying information about the GC ecosystem., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Kinesiology Taping(KT) is commonly used as a physical therapy to prevent exercise-induced fatigue. This study aims to evaluate the immediate effects of KT on muscle strength, static balance, and proprioception after eccentric muscle fatigue on ankle., Methods: Twenty healthy male university students were recruited. The experimental protocol was structured into four sessions, each separated by a one-week washout period to prevent carryover effects. Participants were randomly allocated to one of four intervention conditions in each session, ensuring no participant received the same intervention twice. These conditions were: no taping(NT),sham taping(ST),athletic taping(AT),and kinesiology taping(KT).Taping was applied immediately following an eccentric muscle fatigue protocol targeting the ankle, and assessments were conducted in the order of proprioception, muscle strength and static balance. Isometric muscle strength and proprioception were evaluated using the Biodex isokinetic system. Static balance was measured using the TecnoBody balance platform., Results: KT had a significantly higher plantarflexion/dorsiflexion peak torque, dorsiflexion average peak torque, and plantarflexion/dorsiflexion average power at 60°/s compared with NT and ST in terms of isometric muscle strength (p < 0.05).Furthermore, the plantarflexion peak torque of KT was significantly greater than AT at 60°/s[p = 0.005,95% confidence interval(CI) = 3.39 to 18.20] and 180°/s[p = 0.006,95%CI(2.62,21.98)]. In terms of proprioception, KT showed a lower absolute error in 25° plantarflexion and 10° dorsiflexion compared to NT, ST and AT. For static balance with eyes-open and eyes-closed conditions, AT and KT had a lower total sway area than NT and ST (p < 0.05). Additionally, a significant difference in total sway length with eyes-open condition was observed between AT and KT[p < 0.001,95%CI(-431.81,-168.25)];total sway area and the center of pressure(COP) velocity in the mediolateral(ML) and anteroposterior(AP) directions with eyes-closed condition were significantly lower in AT compared to KT., Conclusion: This study suggests that KT is more effective than other taping conditions in improving muscle strength and proprioception after eccentric muscle fatigue on ankle. However, AT is more helpful in increasing static postural control ability after ankle muscle fatigue than KT., Trial Registration: This study was registered with www.chictr.org.cn (registration number: ChiCTR2300068278) on 13/2/2023., (© 2024. The Author(s).)

Tumor cell stemness stands out as a pivotal factor driving tumor recurrence or metastasis and significantly contributes to the mortality of patients with colorectal cancer (CRC). Recent research has unveiled a link between immune-active cells and the induction of tumor cell stemness, ultimately leading to heightened resistance to treatment. In this study, stemness in CRC cell lines was assessed after co-culture with natural killer (NK) cells, both with and without sulfarotene administration. Furthermore, a CRC xenograft model was utilized to scrutinize the in vivo efficacy of sulfarotene in overcoming stemness induced by NK cell activation. As a result, CRC cells exhibited significant stemness after NK cell co-culture, as evidenced by the upregulation of several stemness markers associated with cancer stem cells. Moreover, these cells demonstrated remarkable resistance to commonly used chemotherapy agents for CRC, such as oxaliplatin and irinotecan. Importantly, sulfarotene effectively reversed the altered stemness of CRC cells in both in vitro and in vivo assays. In conclusion, sulfarotene emerges as a promising therapeutic strategy for overcoming colorectal cancer resistance to NK cells by effectively inhibiting stemness remodeling. This study underscores the potential of sulfarotene in augmenting NK-cell-mediated immune surveillance, proposing a novel immunotherapeutic approach against colorectal cancer.

Purpose: Tuberculous sclerosis complex (TSC) is an autosomal dominant multi-system disease. In TSC patients, the inhibition of mTOR pathway is weakened, which leads to the uncontrolled proliferation of normal resting cells. Therefore, mTOR inhibitors have many therapeutic potentials in the treatment of TSC. However, there is no consensus on the safety and efficacy of mTOR inhibitors so far. This article aimed to present new evidence for the efficacy and safety of mTOR inhibitors in the treatment of TSC by evaluating published clinical trials., Methods: A systemic search of online databases, such as Cochrane Library, Embase, PubMed, and the US National Institutes of Health Clinical Trials Registry, was conducted. The researchers selected studies that met the following entry criteria: randomized, double-blinded or single-blinded, placebo-controlled, parallel-group studies with active and control arms receiving rapamycin or everolimus and matched placebo, respectively. The meta-analysis included seven studies. Tumor response or epilepsy seizure frequency response rates were considered efficacy outcomes., Results: In seven studies involving 877 patients, using of mTOR inhibitors therapy showed an improvement in both tumor response and seizure frequency outcomes in TSC. In combination of AML (angiomyolipomas), SEGA (subependymal giant cell astrocytoma), epilepsy, and facial angiofibroma subjects, the RR is 3.01 (95% CI 2.03 to 4.45, p = 0.000) with observed heterogeneity (I-squared = 55.4%). The main side effect of mTOR inhibitors was stomatitis., Conclusion: The updated meta-analysis suggests that the use of mTOR inhibitors is an effective therapy for patients with TSC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bisphenol AF (BPAF) is extensively used in industrial production as an emerging substitute for the earlier-used bisphenol A (BPA). Studies have found that BPAF had stronger estrogenic activities than BPA. However, the effects of BPAF on the luteal function of pregnancy and its possible mechanisms are largely unknown. In this study, pregnant mice were orally administered 3.0 and 30 mg/kg/day of BPAF from gestational day (GD) 1 to 8, and samples were collected on GD 8 and GD 19. Results showed that maternal exposure to BPAF impaired embryo implantation and reduced ovarian weight, and interfered with steroid hormone secretion, and decreased the numbers and areas of corpus luteum. BPAF treatment significantly down-regulated expression levels of ovarian Star, Cyp11a, Hsd3b1, and Cyp19a1 mRNA and CYP19a1 and ERα proteins. BPAF also disrupted markers of redox/inflammation key, including silent information regulator of transcript-1 (SIRT-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-B (NF-ĸB) expressions along with reduced ovarian antioxidant (CAT and SOD) capacity, enhanced oxidant (H 2 O 2 and MDA) and inflammatory factor (Il6 and Tnfa) activities. Furthermore, BPAF exposure inhibited macrophages with a pro-angiogenic phenotype that specifically expressed TIE-2, accompanied by inhibition of angiogenic factors (HIF1a, VEGFA, and Angpt1) and promotion of anti-angiogenic factor Ang-2 to suppress luteal angiogenesis. In addition, BPAF administration also induced luteolysis and apoptosis by up-regulation of COX-2, BAX/BCL-2, and Cleaved-Caspase-3 protein. Collectively, our current data demonstrated that gestational exposure to BPAF caused luteal endocrine disorder by altering ovarian SIRT-1/Nrf2/NF-kB expressions and macrophage proangiogenic function in mice., 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 © 2023 Elsevier Inc. All rights reserved.)

Rationale & Objective: This study aimed to assess the effect of exposure to organic pollutants in adults with chronic kidney disease (CKD)., Study Design: This was a cross-sectional and longitudinal analysis., Setting and Participants: Forty adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC)., Exposures: Exposure at baseline and longitudinally to various organic chemical pollutants., Outcomes: The outcomes were as follows: death; composite of congestive heart failure, myocardial infarction, and stroke; event-free survival from kidney failure or ≥50% decline in estimated glomerular filtration rate (eGFR); and longitudinal trajectory of eGFR., Analytical Approach: We used high-performance liquid chromatography with tandem mass spectrometry to measure urinary concentrations of bisphenols, phthalates, organophosphate pesticides, polycyclic aromatic hydrocarbons, melamine, and cyanuric acid at years 1, 3, and 5 after enrollment in the CRIC. Univariate and multivariable logistic regression were used to examine the association of individual compounds and classes of pollutants with the outcomes. The Cox proportional hazards model and Kaplan-Meier method were used to calculate hazard ratios and 95% CIs for each class of pollutants., Results: Median baseline eGFR and urinary protein-to-creatinine ratio were 33 mL/min/1.73 m 2 and 0.58 mg/g, respectively. Of 52 compounds assayed, 30 were detectable in ≥50% of participants. Urinary chemical concentrations were comparable in patients with CKD and healthy individuals from contemporaneous National Health and Nutrition Examination Survey cohorts. Phthalates were the only class with a trend toward higher exposure in patients with CKD. There was an inverse relationship between exposure and the eGFR slopes for bisphenol F, mono-(3-carboxypropyl) phthalate, mono-benzyl phthalate, mono-[2-(carboxymethyl)hexyl] phthalate, and melamine. There were no associations between organic pollutant exposure and cardiovascular outcomes., Limitations: Small sample size, evaluation of single rather than combined exposures., Conclusions: Simultaneous measurement of multiple organic pollutants in adults with CKD is feasible. Exposure levels are comparable with healthy individuals. Select contaminants, especially in the phthalate class, may be associated with more rapid deterioration in kidney function., (© 2023 The Authors.)

Currently, platinum-containing regimens are the most commonly used regimens for advanced gastric cancer patients, and chemotherapy resistance is one of the main reasons for treatment failure. Thus, it is important to reveal the mechanism of oxaliplatin resistance and to seek effective intervention strategies to improve chemotherapy sensitivity, thereby improving the survival and prognosis of gastric cancer patients. To understand the molecular mechanisms of oxaliplatin resistance, we generate an oxaliplatin-resistant gastric cancer cell line and conduct assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) for both parental and oxaliplatin-resistant AGS cells. A total of 3232 genomic regions are identified to have higher accessibility in oxaliplatin-resistant cells, and DNA-binding motif analysis identifies JUNB as the core transcription factor in the regulatory network. JUNB is overexpressed in oxaliplatin-resistant gastric cancer cells, and its upregulation is associated with poor prognosis in gastric cancer patients, which is validated by our tissue microarray data. Moreover, chromatin immunoprecipitation sequencing (ChIP-seq) analysis reveals that JUNB binds to the transcriptional start site of key genes involved in the MAPK signaling pathway. Knockdown of JUNB inhibits the MAPK signaling pathway and restores sensitivity to oxaliplatin. Combined treatment with the ERK inhibitor piperlongumine or MEK inhibitor trametinib effectively overcomes oxaliplatin resistance. This study provides evidence that JUNB mediates oxaliplatin resistance in gastric cancer by activating the MAPK pathway. The combination of MAPK inhibitors with oxaliplatin overcomes resistance to oxaliplatin, providing a promising treatment opportunity for oxaliplatin-resistant gastric cancer patients.

Background: Living in neighborhoods with higher levels of walkability has been associated with a reduced risk of obesity and higher levels of physical activity. Obesity has been linked to increased risk of 13 cancers in women. However, long-term prospective studies of neighborhood walkability and risk for obesity-related cancer are scarce., Objectives: We evaluated the association between long-term average neighborhood walkability and obesity-related cancer risk in women., Methods: The New York University Women's Health Study (NYUWHS) is a prospective cohort with 14,274 women recruited between 1985 and 1991 in New York City and followed over nearly three decades. We geocoded residential addresses for each participant throughout follow-up and calculated an average annual measure of neighborhood walkability across years of follow-up using data on population density and accessibility to destinations associated with geocoded residential addresses. We used ICD-9 codes to characterize first primary obesity-related cancers and employed Cox proportional hazards models to assess the association between average neighborhood walkability and risk of overall and site-specific obesity-related cancers., Results: Residing in neighborhoods with a higher walkability level was associated with a reduced risk of overall and site-specific obesity-related cancers. The hazards ratios associated with a 1-standard deviation increase in average annual neighborhood walkability were 0.88 (95% CI: 0.85, 0.93) for overall obesity-related cancer, 0.89 (95% CI: 0.84, 0.95) for postmenopausal breast cancer, 0.82 (95% CI: 0.68, 0.99) for ovarian cancer, 0.87 (95% CI: 0.76, 0.99) for endometrial cancer, and 0.68 (95% CI: 0.49, 0.94) for multiple myeloma, adjusting for potential confounders at both the individual and neighborhood level. The association between neighborhood walkability and risk of overall obesity-related cancer was stronger among women living in neighborhoods with higher levels of poverty compared with women living in areas with lower poverty levels ( p Interaction = 0.006 )., Discussion: Our study highlights a potential protective role of neighborhood walkability in preventing obesity-related cancers in women. https://doi.org/10.1289/EHP11538.

Studying time-dependent exposure mixtures has gained increasing attentions in environmental health research. When a scalar outcome is of interest, distributed lag (DL) models have been employed to characterize the exposures effects distributed over time on the mean of final outcome. However, there is a methodological gap on investigating time-dependent exposure mixtures with different quantiles of outcome. In this paper, we introduce semiparametric partial-linear single-index (PLSI) DL quantile regression, which can describe the DL effects of time-dependent exposure mixtures on different quantiles of outcome and identify susceptible periods of exposures. We consider two time-dependent exposure settings: discrete and functional, when exposures are measured in a small number of time points and at dense time grids, respectively. Spline techniques are used to approximate the nonparametric DL function and single-index link function, and a profile estimation algorithm is proposed. Through extensive simulations, we demonstrate the performance and value of our proposed models and inference procedures. We further apply the proposed methods to study the effects of maternal exposures to ambient air pollutants of fine particulate and nitrogen dioxide on birth weight in New York University Children's Health and Environment Study (NYU CHES)., (© 2022 The International Biometric Society.)

Detecting and characterizing subgroups with differential effects of a binary treatment has been widely studied and led to improvements in patient outcomes and population risk management. Under the setting of a continuous treatment, however, such investigations remain scarce. We propose a semiparametric change-plane model and consequently a doubly robust test statistic for assessing the existence of two subgroups with differential treatment effects under a continuous treatment. The proposed testing procedure is valid when either the baseline function for the covariate effects or the generalized propensity score function for the continuous treatment is correctly specified. The asymptotic distributions of the test statistic under the null and local alternative hypotheses are established. When the null hypothesis of no subgroup is rejected, the change-plane parameters that define the subgroups can be estimated. This paper provides a unified framework of the change-plane method to handle various types of outcomes, including the exponential family of distributions and time-to-event outcomes. Additional extensions with nonparametric estimation approaches are also provided. We evaluate the performance of our proposed methods through extensive simulation studies under various scenarios. An application to the Health Effects of Arsenic Longitudinal Study with a continuous environmental exposure of arsenic is presented., (© 2022 The International Biometric Society.)

Study Objective: To study associations between nighttime sleep characteristics and time to pregnancy., Methods: Pregnant people age ≥18 years and<18 weeks' gestation were recruited from 3 New York University Grossman School of Medicine affiliated hospitals in Manhattan and Brooklyn (n = 1428) and enrolled into the New York University Children's Health and Environment Study. Participants in the first trimester of pregnancy were asked to recall their time to pregnancy and their sleep characteristics in the 3 months before conception., Results: Participants who reported sleeping<7 hours per night tended to have shorter time to pregnancy than those who slept 7-9 hours per night (adjusted fecundability odds ratio = 1.16, 95% confidence interval: 0.94, 1.41). Participants with a sleep midpoint of 4 AM or later tended to have longer time to pregnancy compared with those with earlier sleep midpoints (before 4 AM) (adjusted fecundability odds ratio = 0.88, 95% confidence interval: 0.74, 1.04). When stratified by sleep midpoint, sleeping<7 hours was significantly associated with shorter time to pregnancy only among those whose sleep midpoint was before 4 AM (adjusted fecundability odds ratio = 1.33, 95% confidence interval: 1.07, 1.67)., Conclusions: The association of sleep duration with time to pregnancy was modified by chronotype, suggesting that both biological and behavioral aspects of sleep may influence fecundability., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

High-risk neuroblastoma exhibits transcriptional activation of the mevalonate pathway that produces cholesterol and nonsterol isoprenoids. A better understanding of how this metabolic reprogramming contributes to neuroblastoma development could help identify potential prevention and treatment strategies. Here, we report that both the cholesterol and nonsterol geranylgeranyl-pyrophosphate branches of the mevalonate pathway are critical to sustain neuroblastoma cell growth. Blocking the mevalonate pathway by simvastatin, a cholesterol-lowering drug, impeded neuroblastoma growth in neuroblastoma cell line xenograft, patient-derived xenograft (PDX), and TH-MYCN transgenic mouse models. Transcriptional profiling revealed that the mevalonate pathway was required to maintain the FOXM1-mediated transcriptional program that drives mitosis. High FOXM1 expression contributed to statin resistance and led to a therapeutic vulnerability to the combination of simvastatin and FOXM1 inhibition. Furthermore, caffeine synergized with simvastatin to inhibit the growth of neuroblastoma cells and PDX tumors by blocking statin-induced feedback activation of the mevalonate pathway. This function of caffeine depended on its activity as an adenosine receptor antagonist, and the A2A adenosine receptor antagonist istradefylline, an add-on drug for Parkinson's disease, could recapitulate the synergistic effect of caffeine with simvastatin. This study reveals that the FOXM1-mediated mitotic program is a molecular statin target in cancer and identifies classes of agents for maximizing the therapeutic efficacy of statins, with implications for treatment of high-risk neuroblastoma., Significance: Caffeine treatment and FOXM1 inhibition can both enhance the antitumor effect of statins by blocking the molecular and metabolic processes that confer statin resistance, indicating potential combination therapeutic strategies for neuroblastoma. See related commentary by Stouth et al., p. 2091., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Air pollution is a health risk in pregnant women and children. Despite the importance of refined exposure assessment, the characterisation of personalised air pollution exposure remains a challenge in paediatric and perinatal epidemiology., Objective: We used portable personal air monitors to characterise personalised exposure to air pollutants in pregnant women., Methods: Between November 2019 and May 2022, we offered personal air monitors to pregnant women participating in a birth cohort in New York City. During pregnancy, women used air monitors, which measured particulate matter (PM), nitrogen dioxide (NO 2 ), and volatile organic compounds (average use = 14 days). Data were stored in real-time on a secure database via synchronisation with a smartphone application. Of 497 women who agreed to use air monitors, 273 women (55%) were successful in using air monitors for longer than a day. For these participants, we identified daily patterns of exposure to air pollutants using functional principal component analysis (3827 days of air monitoring)., Results: Compared to women with no pollution data (n = 224), women who successfully used monitors were more likely to be non-Hispanic White and Asian (vs. Hispanic), nulliparous, unemployed, married/partnered, and received the device in-person (vs. mailed). We identified different daily patterns of exposure to air pollutants. The most dominant pattern for all pollutants was low exposure levels with little variations within 24 h, followed by a pattern that showed differences between day and night levels. NO 2 had higher daily variations compared to PM., Conclusions: Small wearables are useful for the measurement of personalised air pollution exposure in birth cohorts and identify daily patterns that cannot be captured otherwise. Successful participation, however, depends on certain individual characteristics. Future studies should consider strategies in design and analysis to account for selective participation., (© 2023 John Wiley & Sons Ltd.)

The emergence of anti-EGFR therapy has revolutionized the treatment of colorectal cancer (CRC). However, not all patients respond consistently well. Therefore, it is imperative to conduct further research to identify the molecular mechanisms underlying the development of cetuximab resistance in CRC. In this study, we find that the expressions of many metabolism-related genes are downregulated in cetuximab-resistant CRC cells compared to their sensitive counterparts. Specifically, acetyl-CoA acyltransferase 2 (ACAA2), a key enzyme in fatty acid metabolism, is downregulated during the development of cetuximab resistance. Silencing of ACAA2 promotes proliferation and increases cetuximab tolerance in CRC cells, while overexpression of ACAA2 exerts the opposite effect. RTK-Kras signaling might contribute to the downregulation of ACAA2 expression in CRC, and ACAA2 predicts CRC prognosis in patients with Kras mutations. Collectively, our data suggest that modulating ACAA2 expression contributes to secondary cetuximab resistance in Kras wild-type CRC patients. ACAA2 expression is related to Kras mutation and demonstrates a prognostic role in CRC patients with Kras mutation. Thus, ACAA2 is a potential target in CRC with Kras mutation.

Background: Isolated small airway abnormalities may be demonstrable at rest in patients with normal spirometry; however, the relationship of these abnormalities to exertional symptoms remains uncertain. This study uses an augmented cardiopulmonary exercise test (CPET) to include evaluation of small airway function during and following exercise to unmask abnormalities not evident with standard testing in individuals with dyspnoea and normal spirometry., Methods: Three groups of subjects were studied: 1) World Trade Center (WTC) dust exposure (n=20); 2) Clinical Referral (n=15); and Control (n=13). Baseline evaluation included respiratory oscillometry. Airway function during an incremental workload CPET was assessed by: 1) tidal flow versus volume curves during exercise to assess for dynamic hyperinflation and expiratory flow limitation; and 2) post-exercise spirometry and oscillometry to evaluate for airway hyperreactivity., Results: All subjects demonstrated normal baseline forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC). Dyspnoea was reproduced during CPET in WTC and Clinical Referral groups versus Control without abnormality in respiratory pattern and minute ventilation. Tidal flow-volume curves uncovered expiratory flow limitation and/or dynamic hyperinflation with increased prevalence in WTC and Clinical Referral versus Control (55%, 87% versus 15%; p<0.001). Post-exercise oscillometry uncovered small airway hyperreactivity with increased prevalence in WTC and Clinical Referral versus Control (40%, 47% versus 0%, p < 0.05)., Conclusions: We uncovered mechanisms for exertional dyspnoea in subject with normal spirometry that was attributable to either small airway dysfunction during exercise and/or small airway hyperreactivity following exercise. The similarity of findings in WTC environmentally exposed and clinically referred cohorts suggests broad relevance for these evaluations., Competing Interests: Conflict of interest: None of the authors have a conflict of interest to declare., (Copyright ©The authors 2023.)

Study Question: How did the first two coronavirus disease 2019 (COVID-19) waves affect fertility rates in the USA?, Summary Answer: States differed widely in how their fertility rates changed following the COVID-19 outbreak and these changes were influenced more by state-level economic, racial, political, and social factors than by COVID-19 wave severity., What Is Known Already: The outbreak of the COVID-19 pandemic contributed to already declining fertility rates in the USA, but not equally across states. Identifying drivers of differential changes in fertility rates can help explain variations in demographic shifts across states in the USA and motivate policies that support families in general, not only during crises., Study Design, Size, Duration: This is an ecological study using state-level data from 50 US states and the District of Columbia (n = 51). The study period extends from 2020 to 2021 with historical data from 2016 to 2019. We identified Wave 1 as the first apex for each state after February 2020 and Wave 2 as the second apex, during Fall/Winter 2020-2021., Participants/materials, Setting, Methods: State-level COVID-19 wave severity, defined as case acceleration during each 3-month COVID-19 wave (cases/100 000 population/month), was derived from 7-day weekly moving average COVID-19 case rates from the US Centers for Disease Control and Prevention (CDC). State-level fertility rate changes (change in average monthly fertility rate/100 000 women of reproductive age (WRA)/year) were derived from the CDC Bureau of Vital Statistics and from 2020 US Census and University of Virginia 2021 population estimates 9 months after each COVID-19 wave. We performed univariate analyses to describe national and state-level fertility rate changes following each wave, and simple and multivariable linear regression analyses to assess the relation of COVID-19 wave severity and other state-level characteristics with fertility rate changes., Main Results and the Role of Chance: Nationwide, fertility dropped by 17.5 births/month/100 000 WRA/year following Wave 1 and 9.2 births/month/100 000 WRA/year following Wave 2. The declines following Wave 1 were largest among majority-Democrat, more non-White states where people practiced greater social distancing. Greater COVID-19 wave severity was associated with steeper fertility rate decline post-Wave 1 in simple regression, but the association was attenuated when adjusted for other covariates. Adjusting for the economic impact of the pandemic (hypothesized mediator) also attenuated the effect. There was no relation between COVID-19 wave severity and fertility rate change following Wave 2., Limitations, Reasons for Caution: Our study harnesses state-level data so individual-level conclusions cannot be inferred. There may be residual confounding in our multivariable regression and we were underpowered to detect some effects., Wider Implications of the Findings: The COVID-19 pandemic initially impacted the national fertility rate but, overall, the fertility rate rebounded to the pre-pandemic level following Wave 2. Consistent with prior literature, COVID-19 wave severity did not appear to predict fertility rate change. Economic, racial, political, and social factors influenced state-specific fertility rates during the pandemic more than the severity of the outbreak alone. Future studies in other countries should also consider whether these factors account for internal heterogeneity when examining the impact of the COVID-19 pandemic and other crises on fertility., Study Funding/competing Interest(s): L.G.K. received funding from the National Institute of Environmental Health Sciences (R00ES030403), M.C. from the National Science Foundation Graduate Research Fellowship Program (20-A0-00-1005789), and M.L. and E.S. from the National Institute of Environmental Health Sciences (R01ES032808). None of the authors have competing interests., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Reproducible translation of transcriptomics data has been hampered by the ubiquitous presence of batch effects. Statistical methods for managing batch effects were initially developed in the setting of sample group comparison and later borrowed for other settings such as survival outcome prediction. The most notable such method is ComBat, which adjusts for batches by including it as a covariate alongside sample groups in a linear regression. In survival prediction, however, ComBat is used without definable groups for survival outcome and is done sequentially with survival regression for a potentially batch-confounded outcome. To address these issues, we propose a new method called BATch MitigAtion via stratificatioN (BatMan). It adjusts batches as strata in survival regression and uses variable selection methods such as the regularized regression to handle high dimensionality. We assess the performance of BatMan in comparison with ComBat, each used either alone or in conjunction with data normalization, in a resampling-based simulation study under various levels of predictive signal strength and patterns of batch-outcome association. Our simulations show that (1) BatMan outperforms ComBat in nearly all scenarios when there are batch effects in the data and (2) their performance can be worsened by the addition of data normalization. We further evaluate them using microRNA data for ovarian cancer from the Cancer Genome Atlas and find that BatMan outforms ComBat while the addition of data normalization worsens the prediction. Our study thus shows the advantage of BatMan and raises caution about the use of data normalization in the context of developing survival prediction models. The BatMan method and the simulation tool for performance assessment are implemented in R and publicly available at LXQin/PRECISION.survival-GitHub.

Background: Sub-cohort sampling designs such as a case-cohort study play a key role in studying biomarker-disease associations due to their cost effectiveness. Time-to-event outcome is often the focus in cohort studies, and the research goal is to assess the association between the event risk and risk factors. In this paper, we propose a novel goodness-of-fit two-phase sampling design for time-to-event outcomes when some covariates (e.g., biomarkers) can only be measured on a subgroup of study subjects., Methods: Assuming that an external model, which can be the well-established risk models such as the Gail model for breast cancer, Gleason score for prostate cancer, and Framingham risk models for heart diseases, or built from preliminary data, is available to relate the outcome and complete covariates, we propose to oversample subjects with worse goodness-of-fit (GOF) based on an external survival model and time-to-event. With the cases and controls sampled using the GOF two-phase design, the inverse sampling probability weighting method is used to estimate the log hazard ratio of both incomplete and complete covariates. We conducted extensive simulations to evaluate the efficiency gain of our proposed GOF two-phase sampling designs over case-cohort study designs., Results: Through extensive simulations based on a dataset from the New York University Women's Health Study, we showed that the proposed GOF two-phase sampling designs were unbiased and generally had higher efficiency compared to the standard case-cohort study designs., Conclusion: In cohort studies with rare outcomes, an important design question is how to select informative subjects to reduce sampling costs while maintaining statistical efficiency. Our proposed goodness-of-fit two-phase design provides efficient alternatives to standard case-cohort designs for assessing the association between time-to-event outcome and risk factors. This method is conveniently implemented in standard software., (© 2023. The Author(s).)

The infections caused by Gram-positive bacteria (G + ) have seriously endangered public heath due to their high morbidity and mortality. Therefore, it is urgent to develop a multifunctional system for selective recognition, imaging and efficient eradication of G + . Aggregation-induced emission materials have shown great promise for microbial detection and antimicrobial therapy. In this paper, a multifunctional ruthenium (II) polypyridine complex Ru2 with aggregation-induced emission (AIE) characteristic, was developed and used for selective discrimination and efficient extermination of G + from other bacteria with unique selectivity. The selective G + recognition benefited from the interaction between lipoteichoic acids (LTA) and Ru2. Accumulation of Ru2 on the G + membrane turned on its AIE luminescence and allowed specific G + staining. Meanwhile, Ru2 under light irradiation also possessed robust antibacterial activity for G + in vitro and in vivo antibacterial experiments. To the best of our knowledge, Ru2 is the first Ru-based AIEgen photosensitizer for simultaneous dual applications of G + detection and treatment, and inspires the development of promising antibacterial agents in the future., 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 © 2023 Elsevier Masson SAS. All rights reserved.)

Capping and oxidation by lanthanum-modified bentonite (LMB) and calcium nitrate (CN) has a dual effect of deep phosphorus (P)/arsenic (As) clearance and surface P/As blockade. However, little information is available on the effect of LMB and CN on heavy metals. In this study, we hypothesize that LMB and CN exerted the same synergistic effect on heavy metals as P and As. We verified this through Rhizon samplers, diffusive gradients in thin films technology (DGT) and planar optode (PO) methods. The results showed that individual and combined LMB and CN treatments temporarily decreased but eventually increased the dissolved oxygen of the sediment-water interface (SWI). DGT-labile sulfide in the surface 110 mm sediment, soluble Fe(II) and DGT-labile Fe(II) in the surface 80 mm sediment were eliminated within 30 days by CN and LMB + CN treatments. A temporary sharp increase in soluble Fe, Mn, Co, and DGT-labile Mn, Co, Cu, and Ni was observed in CN and LMB + CN groups probably due to sulfide oxidation and carbonate dissolution. LMB + CN group showed a less-intense increase in DGT-labile metals and less metal release than the CN group (inferred from the total metal content). This indicates that LMB and CN had a synergistic effect on heavy metals. When using the LMB + CN treatment, LMB partly adsorbed and blocked metal release in sulfide and carbonate bound forms and finally transformed them into Fe and Mn oxides and residual forms. We suggest that CN should be combined with capping agents (at an appropriate pH) to compact sediments and block metal exchange at the SWI., 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 © 2023 Elsevier B.V. All rights reserved.)

Purpose: Lamina cribrosa (LC) deformation is hypothesized to play a major role in glaucoma pathogenesis. The purpose of this study was to determine in vivo how varying intraocular pressure (IOP) under fixed intracranial pressure (ICP), and vice versa, deforms the pore paths throughout the LC volume., Methods: Spectral-domain optical coherence tomography scans of the optic nerve head were acquired from healthy adult rhesus monkeys under different pressures. IOP and ICP were controlled with gravity-based perfusion systems into the anterior chamber and lateral ventricle, respectively. IOP and ICP were modulated from baseline to high (19-30 mmHg) and highest (35-50 mmHg) levels while maintaining a fixed ICP of 8 to 12 mmHg and IOP of 15 mmHg, respectively. After three-dimensional registration and segmentation, the paths of pores visible in all settings were tracked based on their geometric centroids. Pore path tortuosity was defined as the measured distance divided by the minimal distance between the most anterior and posterior centroids., Results: The median pore tortuosity at baseline varied among the eyes (range, 1.16-1.68). For the IOP effect under fixed ICP (six eyes, five animals), two eyes showed statistically significant increased tortuosity and one showed a decrease (P < 0.05, mixed-effects model). No significant change was detected in three eyes. When modulating ICP under fixed IOP (five eyes, four animals), a similar response pattern was detected., Conclusions: Baseline pore tortuosity and the response to acute pressure increase vary substantially across eyes., Translational Relevance: LC pore path tortuosity could be associated with glaucoma susceptibility.

Background: Bisphenols and phthalates are high production volume chemicals used as additives in a variety of plastic consumer products leading to near ubiquitous human exposure. These chemicals have established endocrine disrupting properties and have been linked to a range of adverse reproductive and developmental outcomes. Here, we investigated exposure in relation to fetal growth., Methods: Participants included 855 mother-fetal pairs enrolled in the population-based New York University Children's Health and Environment Study (NYU CHES). Bisphenols and phthalates were measured in maternal urine collected repeatedly during pregnancy. Analyses included 15 phthalate metabolites and 2 bisphenols that were detected in 50 % of participants or more. Fetal biometry data were extracted from electronic ultrasonography records and estimated fetal weight (EFW) was predicted for all fetuses at 20, 30, and 36 weeks gestation. We used quantile regression adjusted for covariates to model exposure-outcome relations across percentiles of fetal weight at each gestational timepoint. We examined sex differences using stratified models., Results: Few statistically significant associations were observed across chemicals, gestational time periods, percentiles, and sexes. However, within gestational timepoints, we found that among females, the molar sums of the phthalates DiNP and DnOP were generally associated with decreases in EFW among smaller babies and increases in EFW among larger babies. Among males, the opposite trend was observed. However, confidence intervals were generally wide at the tails of the distribution., Conclusion: In this sample, exposure to bisphenols and phthalates was associated with small sex-specific shifts in fetal growth; however, few associations were observed at the median of fetal weight and confidence intervals in the tails were wide. Findings were strongest for DiNP and DnOP, which are increasingly used as replacements for DEHP, supporting the need for future research on these contaminants., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Whitney Cowell reports financial support was provided by National Institutes of Health. Linda Kahn reports financial support was provided by National Institutes of Health. Leonardo Trasande reports financial support was provided by National Institutes of Health]., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Glyphosate-based herbicides (GBHs) are the most widely used agrochemicals worldwide, increasing the risk of their occurrence in the environment. This study aimed to explore effects and mechanisms of GBH exposure on placental development in vivo during pregnancy in mice. Pregnant mice received GBH by gavage at 0, 5, and 50 mg⋅kg -1 ⋅day -1 doses from gestational day (GD) 1 to GD 13 and were sacrificed on GD 13 or GD19. Our data indicated that GBH administration significantly increased the number of resorbed fetuses, reduced the weight of fetuses and placentas, and inhibited placental growth, as evident from decreased placental total area and spongiotrophoblast area on GD 19. GBH treatment also inhibited proliferation and induced apoptosis of placenta via upregulation of Bax, cleaved caspase-3 and -12 expression, and downregulation of B cell lymphoma (Bcl)-2 expression. Further study showed that GBH exposure significantly increased expression levels of glucose-regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) mRNAs and proteins and triggered oxidative stress in placenta on GD 13 and GD 19. In conclusion, our findings suggest that maternal exposure to GBH can impair placental development through the endoplasmic reticulum stress-mediated activation of GRP78/PERK/CHOP signaling pathway in mice., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR), is effective for RAS wild-type metastatic colorectal cancer (mCRC) patients. However, cetuximab resistance often occur and the mechanism has not been fully elucidated. The purpose of this study was to investigate the role of asparaginyl endopeptidase (AEP) in cetuximab resistance., Methods: Differentially expressed genes between cetuximab responders and non-responders were identified by analyzing the gene expression profile GSE5851, retrieved from Gene Expression Omnibus (GEO). The potential genes were further validated in cetuximab-resistant CRC cell lines. The expression of AEP in the peripheral blood and tumor tissues of mCRC patients in our hospital were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The survival analysis was carried out by Kaplan-Meier method. The function and associated pathways of AEP were further investigated by lentivirus transfection, CCK8 assay, colony formation assay, real-time polymerase chain reaction (qPCR) and western blot., Results: Through bioinformatics analysis, we found that the expression of AEP gene was related to progress free survival (PFS) of mCRC patients treated with cetuximab alone (P = 0.00133). The expression of AEP was significantly higher in the cetuximab-resistant CRC cell lines, as well as in mCRC patients with shorter PFS treated with cetuximab-containing therapy. Furthermore, AEP could decrease the sensitivity of CRC cells to cetuximab in vitro. And the phosphorylation level of MEK and ERK1/2 was increased in AEP overexpression cells. The downregulation of AEP using specific inhibitors could partially restore the sensitivity of CRC cells to cetuximab., Conclusion: The higher expression of AEP could contribute to the shorter PFS of cetuximab treatment in mCRC. The reason might be that AEP could promote the phosphorylation of MEK/ERK protein in the downstream signal pathway of EGFR., (© 2023. The Author(s).)

It is increasingly important to study the impact of environmental inhalation exposures on human health in natural or man-made disasters in civilian populations. The members of the World Trade Center Environmental Health Center (WTC EHC; WTC Survivors) had complex exposures to environmental disaster from the destruction of WTC towers and can serve to reveal the effects of WTC exposure on the entire spectrum of lung functions. We aimed to investigate the associations between complex WTC exposures and measures of spirometry and oscillometry in WTC Survivors and included 3605 patients enrolled between Oct 1, 2009 and Mar 31, 2018. We performed latent class analysis and identified five latent exposure groups. We applied linear and quantile regressions to estimate the exposure effects on the means and various quantiles of pre-bronchodilator (BD) % predicted forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC ratio, as well as the resistance at an oscillating frequency of 5 Hz (R 5 ), frequency dependence of resistance R 5-20 , and reactance area (AX). Compared with Group 5, which had low or unknown exposure and was treated as the reference group, Group 1, the local workers with both acute and chronic exposures, had a lower median of % predicted FVC (-3.6; 95% CI: -5.4, -1.7) and higher (more abnormal) measures of AX at 10th quantile (0.77 cmH 2 O L -1 s; 95% CI: 0.41, 1.13) and 25th quantile (0.80 cmH 2 O L -1 s; 95% CI: 0.41, 1.20). Results suggested heterogeneous exposures to the WTC disaster had differential effects on the distributions of lung functions in the WTC Survivors. These findings could provide insights for future investigation of environmental disaster exposures., (© 2023. The Author(s).)

Background: Regular exercise has been shown to have a beneficial effect on primary osteoporosis (POP). However, current exercise prescriptions have limitations such as insufficient individualized features and low participant compliance, which in turn limit their application in clinical practice. In this study, we propose to establish a personalized exercise prescription based on the Chinese traditional exercise-Yi Jin Jing, combined with treadmill exercises and strength training, and then observe its effects on pain, muscle strength, balance, bone mineral density (BMD) and bone metabolic indexes in patients with POP., Methods: This trial is a single-center, randomized, assessor-blinded, controlled clinical study. We will recruit 40 patients with POP and assign them to the control group and the experimental group in a 1:1 ratio according to the intended protocol. The control group received 24 weeks of conventional medication and health promotion, and the experimental group received 24 weeks of personalized exercise prescription intervention (Yijinjing, treadmill exercises, and strength training). Outcome measures include pain (visual analogue scale), muscle strength (bilateral upper limb grip strength and isometric muscle strength of the trunk, hip, and knee), balance (Balance test with eyes open and closed while standing on one leg), and BMD (Lumbar spine 2-4 and femoral neck). In addition, bone metabolism indicators include parathyroid hormone, osteocalcin, 25-hydroxyvitamin D3 (1,25(OH) 2D3), type I procollagen aminoterminal peptide and type I collagen carboxy-terminal peptide. Outcome measures will be assessed before and after 24 weeks of intervention. Statistical analysis was performed by SPSS22.0., Discussion: This trial aimed to enrich the content and form of exercise rehabilitation prescriptions for patients with POP, which is conducive to improving the exercise rehabilitation effect and quality of life in this population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Particulate matter (PM) exposure is responsible for seven million deaths annually and has been implicated in the pathogenesis of respiratory infections such as severe acute respiratory syndrome (SARS). Understanding modifiable risk factors of high mortality, resource burdensome C19 and exposure risks such as PM is key to mitigating their devastating effects. This systematic review focuses on the literature available, identifying the spatial and temporal variation in the role of quantified PM exposure in SARS disease outcome and planning our future experimental studies., Methods: The systematic review utilized keywords adhered to the PRISMA guidelines. We included original human research studies in English., Results: Initial search yielded N = 906, application of eligibility criteria yielded N = 46. Upon analysis of risk of bias N = 41 demonstrated high risk. Studies found a positive association between elevated PM 2.5 , PM 10 and SARS-related outcomes. A geographic and temporal variation in both PM and C19's role was observed., Conclusion: C19 is a high mortality and resource intensive disease which devastated the globe. PM exposure is also a global health crisis. Our systematic review focuses on the intersection of this impactful disease-exposure dyad and understanding the role of PM is important in the development of interventions to prevent future spread of viral infections.