Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial.

Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

Trends in Reported Calcium and Magnesium Intake from Diet and Supplements by Demographic Factors: National Health and Nutrition Examination Survey, 2003-2018.

BACKGROUND: Calcium and magnesium are important micronutrients necessary for normal body functioning. OBJECTIVE: The objective of the study was to approximate usual nutrient intakes and estimate proportion of adults meeting the estimated average requirement (EAR) of calcium and magnesium from diet, and diet plus supplements (total intake). Trends in the proportion of adults meeting the EAR were estimated by sex, age, and race and ethnicity. DESIGN: The study utilized data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of the United States civilian and noninstitutionalized population. PARTICIPANTS AND SETTING: The continuous NHANES survey data from 2003-2004 through 2017-2018 for dietary intake, and 2007-2008 through 2017-2018 for total intake were analyzed. The study sample included males and females (not lactating/pregnant) aged ≥19 years with two reliable 24-hour dietary recalls and energy intake >500 - <6000 kcal/day (n=35,037). MAIN OUTCOME MEASURES: Mean daily intake and trends of proportion of adults meeting/exceeding the EAR for calcium and magnesium were estimated. STATISTICAL ANALYSES PERFORMED: The National Cancer Institute's (NCI) method was used to calculate daily intakes for calcium and magnesium by demographic subgroups. SAS SURVEYMEAN AND SURVEYFREQ procedures were used to estimate means and standard errors (SE) for continuous variables and frequencies and percentages for categorical variables, and two sample t-test for p-values. Trends were estimated with NCI's Joinpoint trend analysis program. RESULTS: Mean daily dietary calcium intake and proportions of adults meeting the EAR from both diet and supplements was lowest among females (859 mg / 61.9%), adults aged ≥71 years (865 mg / 60.3%) and non-Hispanic black (NHB) individuals (782 mg / 48.6%) compared to males, younger age groups and other races and ethnicities. Magnesium intake reported from diet was lowest in adults ≥71 years (276 mg) while total magnesium intake and proportion of meeting the EAR from both diet and supplements was lowest in females (302 mg) and males (52%) respectively, adults 19-30 years (305 mg / 48.5%) and NHB individuals (274 mg / 35.5%). The trends in the proportion of females and NH white (NHW) adults meeting the EAR from total calcium intake decreased significantly (p-value <0.05) by 2.9% and 2.0% respectively. CONCLUSIONS: Females and adults aged ≥71 years had the lowest reported mean daily dietary calcium intake and proportion meeting the EAR for calcium from diet and supplements. Males and adults aged 19-30 years had the lowest proportion meeting the EAR for magnesium from diet and supplements with adults aged 19-30 years also having the lowest reported total magnesium intake from diet and supplements. NHB individuals had the lowest proportion of meeting the EARs for calcium and magnesium from reported total intake. The trends in the proportion of females and NHW individuals meeting the EARs for calcium through total intake decreased over time and remained stable in other subpopulations and for magnesium.

Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer.

Introduction: Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC and explore the effects and potential treatment by disulfidptosis-related risk stratification. Methods: The disulfidptosis-related genes were first analyzed in bulk RNA-Seq and a prognostic nomogram was developed and validated by LASSO algorithm and multivariate cox regression. Then we systematically assessed the clinicopathological and mutational characteristics, pathway enrichment analysis, immune cell infiltration, single-cell-level expression, and drug sensitivity according to DRPS. Results: The DRPS was established with 6 genes (MYL6, PDLIM1, ACTN4, FLNB, SLC7A11, and CD2AP) and the corresponding prognostic nomogram was constructed based on the DRPS, FIGO stage, grade, and residual disease. Stratified by the risk score derived from DRPS, patients in high-risk group tended to have worse prognosis, lower level of disulfidptosis, activated oncogenic pathways, inhibitory tumor immune microenvironment, and higher sensitivity to specific drugs including epirubicin, stauroporine, navitoclax, and tamoxifen. Single-cell transcriptomic analysis revealed the expression level of genes in the DRPS significantly varied in different cell types between tumor and normal tissues. The protein-level expression of genes in the DRPS was validated by the immunohistochemical staining analysis. Conclusion: In this study, the DRPS and corresponding prognostic nomogram for OC were developed, which was important for OC prognostic assessment, tumor microenvironment modification, drug sensitivity prediction, and exploration of potential mechanisms in tumor development.

Corrigendum to "SEMA4D acts as a novel oligogenic pathogenic gene of idiopathic hypogonadotropic hypogonadism through the PlexinB1/MET/RND1/RHOA/RAF1/MAPK signaling axis" [Genes & Diseases 10 (2023) 65-68].

[This corrects the article DOI: 10.1016/j.gendis.2022.05.030.].

Intimate Partner Violence and Antenatal Depression Among Underserved Pregnant Women.

Introduction: Few studies have examined the associations of intimate partner violence (IPV) exposure during pregnancy and types of IPV with antenatal depression among underserved pregnant women. Methods: Data came from participants from a Healthy Start program in South Carolina between 2015 and 2019 (n = 1,629). The first two questions in the Woman Abuse Screening Tool (WAST) were used to measure IPV exposure, that is, having a problematic relationship with their partner. Those who had IPV exposure were assessed with six additional questions of the WAST. Principal component analysis was conducted on the 8-item WAST data to identify underlying types of IPV exposure. Antenatal depression was defined as the Center for Epidemiologic Studies Depression scores ≥16. Results: Participants were racially diverse (71% black, 21% white) with 85% Medicaid recipients. Nearly 12% of participants reported IPV exposure and 30% reported antenatal depression. The odds of having IPV exposure were higher among unmarried women, those with less than a high school education, and those who lacked family support. The odds of having antenatal depression were 2.5 times higher (95% CI: 1.9-3.5) among women with IPV exposure. After controlling for covariates, a one-point increase in the scores for psychological IPV (Factor 1) or a problematic relationship (Factor 3) was associated with increased odds of antenatal depression. Conclusion: This is one of the first studies to estimate the prevalence of IPV exposure using a proxy measure (a problematic relationship) among underserved U.S. pregnant women. Its positive association with antenatal depression suggests the utility of screening for a problematic relationship using a two-item WAST and providing assistance to those with IPV exposure.

Associations between sleep duration, sleep disturbance and cardiovascular disease biomarkers among adults in the United States.

BACKGROUND: Sleep problems are associated with abnormal cardiovascular biomarkers and an increased risk of cardiovascular diseases (CVDs). However, studies investigating associations between sleep problems and CVD biomarkers have reported conflicting findings. This study examined the associations between sleep problems and CVD biomarkers in the United States. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) (2007-2018) and analyses were restricted to adults ≥ 20 years (n = 23,749). CVD biomarkers [C-reactive Protein (CRP), low-density lipoproteins, high-density lipoproteins (HDL), triglycerides, insulin, glycosylated hemoglobin (HbA1c), and fasting blood glucose] were categorized as abnormal or normal using standardized cut-off points. Sleep problems were assessed by sleep duration (short [≤ 6 h], long [≥ 9 h], and recommended [> 6 to < 9 h) and self-reported sleep disturbance (yes, no). Multivariable logistic regression models explored the associations between sleep duration, sleep disturbance, and CVD biomarkers adjusting for sociodemographic characteristics and lifestyle behaviors. RESULTS: The mean sleep duration was 7.1 ± 1.5 h and 25.1% of participants reported sleep disturbances. Compared to participants with the recommended sleep duration, those with short sleep duration had higher odds of abnormal levels of HDL (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.05-1.39), CRP (aOR = 3.08, 95% CI = 1.18-8.05), HbA1c (aOR = 1.25, 95% CI = 1.05-1.49), and insulin (aOR = 1.24, 95% CI = 1.03-1.51). Long sleep duration was associated with increased odds of abnormal CRP (aOR = 6.12, 95% CI = 2.19-17.15), HbA1c (aOR = 1.54, 95% CI = 1.09-2.17), and blood glucose levels (aOR = 1.45, 95% CI = 1.07-1.95). Sleep disturbance predicted abnormal triglyceride (aOR = 1.18, 95% CI = 1.01-1.37) and blood glucose levels (aOR = 1.24, 95% CI = 1.04-1.49). CONCLUSION: Short and long sleep durations were positively associated with abnormal CRP, HDL, HbA1c, blood glucose, and insulin levels, while sleep disturbance was associated with abnormal triglyceride and blood glucose levels. Since sleep is a modifiable factor, adopting healthy sleeping habits may create a balanced metabolism and reduce the risk of developing a CVD. Our study may provide insights into the relationship between sleep duration, sleep disturbance, and CVD risk.

Antenatal depressive symptoms and adverse birth outcomes in healthy start participants: The modifying role of utilization of mental health services.

OBJECTIVE: We examined the association between antenatal depressive symptoms and adverse birth outcomes in Midland Healthy Start (MHS) participants and determined whether receiving mental health services reduced the odds of adverse outcomes among those with elevated antenatal depressive symptoms. METHOD: Data from a retrospective cohort of participants (N = 1,733) served by the MHS in South Carolina (2010-2019) were linked with their birth certificates. A score of ≥16 on the Center for Epidemiologic Studies Depression Scale was defined as elevated antenatal depressive symptoms. Services provided by MHS were categorized into: (1) receiving mental health services, (2) receiving other services, and (3) not receiving any services. Adverse birth outcomes included preterm birth, low birth weight, and small for gestational age. RESULTS: Around 31 % had elevated antenatal depressive symptoms. The prevalences of preterm birth, low birthweight, and small for gestational age were 9.5 %, 9.1 %, and 14.6 %, respectively. No significant associations were observed between elevated depressive symptoms and adverse outcomes. Among women with elevated antenatal depressive symptoms, the odds for small for gestational age were lower in those who received mental health services (AOR 0.33, 95 % CI 0.15-0.72) or other services (AOR 0.34, 95 % CI 0.16-0.74) compared to those who did not receive any services. The odds for low birth weight (AOR 0.34, 95 % CI 0.13-0.93) were also lower in those who received mental health services. CONCLUSIONS: Receiving screening and referral services for antenatal depression reduced the risks of having small for gestational age or low birth weight babies among MHS participants.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). CONCLUSION: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

Revealing the mechanism of ethyl acetate extracts of Semen Impatientis against prostate cancer based on network pharmacology and transcriptomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer (PCa) is the most common malignancy of the male genitourinary system and currently lacks effective treatment. Semen Impatientis, the dried ripe seed of Impatiens balsamina L., is described by the Chinese Pharmacopoeia as a traditional Chinese medicine (TCM) and is used in clinical practice to treat tumors, abdominal masses, etc. In our previous study, the ethyl acetate extracts of Semen Impatientis (EAESI) was demonstrated to be the most effective extract against PCa among various extracts. However, the biological effects of EAESI against PCa in vivo and the specific antitumor mechanisms involved remain unknown. AIM OF THE STUDY: In this study, we aimed to investigate the antitumor effect of EAESI on PCa in vitro and in vivo by performing network pharmacology analysis, transcriptomic analysis, and experiments to explore and verify the underlying mechanisms involved. MATERIALS AND METHODS: The antitumor effect of EAESI on PCa in vitro and in vivo was investigated via CCK-8, EdU, flow cytometry, and wound healing assays and xenograft tumor models. Network pharmacology analysis and transcriptomic analysis were employed to explore the underlying mechanism of EAESI against PCa. Activating transcription factor 3 (ATF3) and androgen receptor (AR) were confirmed to be the targets of EAESI against PCa by RT‒qPCR, western blotting, and rescue assays. In addition, the interaction between ATF3 and AR was assessed by coimmunoprecipitation, immunofluorescence, and nuclear-cytoplasmic separation assays. RESULTS: EAESI decreased cell viability, inhibited cell proliferation and migration, and induced apoptosis in AR+ and AR- PCa cells. Moreover, EAESI suppressed the growth of xenograft tumors in vivo. Network pharmacology analysis revealed that the hub targets of EAESI against PCa included AR, AKT1, TP53, and CCND1. Transcriptomic analysis indicated that activating transcription factor 3 (ATF3) was the most likely critical target of EAESI. EAESI downregulated AR expression and decreased the transcriptional activity of AR through ATF3 in AR+ PCa cells; and EAESI promoted the expression of ATF3 and exerted its antitumor effect via ATF3 in AR+ and AR- PCa cells. CONCLUSIONS: EAESI exerts good antitumor effects on PCa both in vitro and in vivo, and ATF3 and AR are the critical targets through which EAESI exerts antitumor effects on AR+ and AR- PCa cells.

Maternal care utilization and provision during the COVID-19 pandemic: Voices from minoritized pregnant and postpartum women and maternal care providers in Deep South.

BACKGROUND: The COVID-19 pandemic has significantly affected maternal care services especially for minoritized individuals, creating challenges for both service users (i.e., African American and Hispanic pregnant/postpartum women) and maternal care providers (MCPs). Guided by a socioecological framework, this study aims to investigate the experiences of African American and Hispanic pregnant and postpartum women, as well as MCPs, in accessing and providing maternal care services during the COVID-19 pandemic in the Deep South. METHODS: We conducted semi-structured interviews with 19 African American women, 20 Hispanic women, and 9 MCPs between January and August 2022. Participants were recruited from Obstetrics and Gynecology clinics, pediatric clinics, and community health organizations in South Carolina, and all births took place in 2021. Interview transcripts were analyzed thematically. RESULTS: Maternal care utilization and provision were influenced by various factors at different socioecological levels. At the intrapersonal level, women's personal beliefs, fears, concerns, and stress related to COVID-19 had negative impacts on their experiences. Some women resorted to substance use as a coping strategy or home remedy for pregnancy-induced symptoms. At the interpersonal level, family and social networks played a crucial role in accessing care, and the discontinuation of group-based prenatal care had negative consequences. Participants reported a desire for support groups to alleviate the pressures of pregnancy and provide a platform for shared experiences. Language barriers were identified as an obstacle for Hispanic participants. Community-level impacts, such as availability and access to doulas and community health workers, provided essential information and support, but limitations in accessing doula support and implicit bias were also identified. At the institutional level, mandatory pre-admission COVID-19 testing, visitation restrictions, and reduced patient-MCP interactions were women's common concerns. Short staffing and inadequate care due to the impact of COVID-19 on the health care workforce were reported, along with anxiety among MCPs about personal protective equipment availability. MCPs emphasized the quality of care was maintained, with changes primarily attributed to safety protocols rather than a decline in care quality. CONCLUSION: The pandemic has disrupted maternal care services. To overcome these issues, health facilities should integrate community resources, adopt telehealth, and develop culturally tailored education programs for pregnant and postpartum women. Supporting MCPs with resources will enhance the quality of care and address health disparities in African American and Hispanic women.

Quantitative proteome and lysine succinylome characterization of zinc chloride smoke-induced lung injury in mice.

The inhalation of zinc chloride (ZnCl2) smoke is one of common resources of lung injury, potentially resulting in severe pulmonary complications and even mortality. The influence of ZnCl2 smoke on lysine succinylation (Ksucc) in the lungs remains uncertain. In this study, we used a ZnCl2 smoke inhalation mouse model to perform global proteomic and lysine succinylome analyses. A total of 6781 Ksucc sites were identified in the lungs, with injured lungs demonstrating a reduction to approximately 2000 Ksucc sites, and 91 proteins exhibiting at least five differences in the number of Ksucc sites. Quantitative analysis revealed variations in expression of 384 proteins and 749 Ksucc sites. The analysis of protein-protein interactions was conducted for proteins displaying differential expression and differentially expressed lysine succinylation. Notably, proteins with altered Ksucc exhibited increased connectivity compared with that in differentially expressed proteins. Beyond metabolic pathways, these highly connected proteins were also involved in lung injury-associated pathological reactions, including processes such as focal adhesion, adherens junction, and complement and coagulation cascades. Collectively, our findings contribute to the understanding of the molecular mechanisms underlaying ZnCl2 smoke-induced lung injury with a specific emphasis on lysine succinylation. These findings could pave the way for targeted interventions and therapeutic strategies to mitigate severe pulmonary complications and mortality associated with such injuries in humans.

Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study.

INTRODUCTION: The prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China. MATERIALS AND METHODS: We analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status. Endpoints were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) algorithm was used to balance the confounding factors. The survival was examined using Kaplan-Meier analysis. Cox proportional hazards regression analyses were used to find prognostic independent risk factors. RESULTS: Among 3715 EC patients, LVSI positive rate was 9.31% (346/3715). After matching, LVSI present group had shorter DFS (P = 0.005), and similar OS (P = 0.656) than LVSI absent group for endometrioid EC patients. For non-endometrioid EC patients, there was no statistical difference in either DFS (P = 0.536) or OS (P = 0.512) after matching. The multivariate Cox analysis showed that LVSI was an independent risk factor of DFS [hazard ratio (HR) 2.62, 95% confidence intervals (CI) 1.35-5.10, P = 0.005] and not OS (HR 1.24, 95%CI 0.49-3.13, P = 0.656) for endometrioid EC patients. It was not a prognostic factor of either DFS (HR 1.28, 95%CI 0.58-2.81, P = 0.539) or OS (HR 1.33, 95%CI 0.55-3.13, P = 0.515) for non-endometrioid EC patients. CONCLUSION: LVSI is an adverse prognostic factor for endometrioid EC patients and has no impact on non-endometrioid EC patients. Necessity of postoperative adjuvant therapy based on LVSI needs to be carefully considered for non-endometrioid EC patients.

Enhancing rice panicle branching and grain yield through tissue-specific brassinosteroid inhibition.

Crop yield potential is constrained by the inherent trade-offs among traits such as between grain size and number. Brassinosteroids (BRs) promote grain size, yet their role in regulating grain number is unclear. By deciphering the clustered-spikelet rice germplasm, we show that activation of the BR catabolic gene BRASSINOSTEROID-DEFICIENT DWARF3 (BRD3) markedly increases grain number. We establish a molecular pathway in which the BR signaling inhibitor GSK3/SHAGGY-LIKE KINASE2 phosphorylates and stabilizes OsMADS1 transcriptional factor, which targets TERMINAL FLOWER1-like gene RICE CENTRORADIALIS2. The tissue-specific activation of BRD3 in the secondary branch meristems enhances panicle branching, minimizing negative effects on grain size, and improves grain yield. Our study showcases the power of tissue-specific hormonal manipulation in dismantling the trade-offs among various traits and thus unleashing crop yield potential in rice.

Efficacy of non-pharmacological interventions for sleep quality in Parkinson's disease: a systematic review and network meta-analysis.

Background: Sleep disorders are one of the most common non-motor symptoms in PD. It can cause a notable decrease in quality of life and functioning in PD patients, as well as place a huge burden on both patients and caregivers. Currently, there are numerous non-pharmacological interventions available to improve sleep quality in PD, with disagreement as to which intervention is most effective. This network meta-analysis was performed to compare and rank non-pharmacological interventions to explore their efficacy in improving sleep quality in PD and to select the best interventions, with a view to providing references and bases for the development of clinical treatments and care programs. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched from inception to December 6, 2023. Two authors independently screened all studies, extracted the data, and evaluated risk of bias of included studies. STATA software version 17.0 was used to conduct the network meta-analysis. Results: Our network meta-analysis included 29 studies involving 1,477 participants and 16 non-pharmacological interventions. Although most nonpharmacological interventions showed non-significant effects, the surface under the cumulative ranking curve (SUCRA) values indicated that the best non-pharmacological intervention for sleep disorders was massage therapy (97.3%), followed by music therapy (94.2%), and Treadmill training (85.7%). Conclusion: Massage therapy can be considered as an effective therapy for improving sleep quality in patients with PD. Due to limited quantity and quality of the included studies, more high quality studies are required to verify the conclusions of this network meta-analysis. Systematic review registration: identifier CRD42023429339, PROSPERO (york.ac.uk).

High effects of climate oscillations on population diversity and structure of endangered Myricaria laxiflora.

Exploring the effects of climate oscillations on the population diversity and structure of endangered organisms in the Three Gorges Reservoir (TGR) area is essential for hydrological environment changes on endangered organism evolution. Myricaria laxiflora is an endemic and endangered shrub restricted to the TGR along the banks of Yangtze River, China. Recently, six natural populations of this species were newly found upstream and downstream of the TGR, whose habitats have been dramatically changed by the summer flooding regulated by large dams. To study the water level fluctuations and climatic shifts on the genetic diversity and genetic differentiation of the six natural populations, 303 individuals from six populations were analyzed based on one nuclear DNA (ITS) and four chloroplast fragments (trnL-F, psbA-trnH, rps16, and rpl16). The phylogenetic tree and significant genetic divergence identified in the cpDNA and ITS with genetic isolation and limited gene flow among regions suggested that the six populations separated well to two groups distributed upstream and downstream. The MaxEnt modeling results indicated that obvious unidirectional eastward migration via Yangtze River gorges watercourse mediated from Last Interglacial to Last Glacial Maximum were showed with the narrow scale distributions of six remnant populations and nine extirpated populations. The initial habitat fragmentation could be triggered by the accumulation of local habitat loss of the impoundment of the TGR during the Present period and might remain stable restoration with bidirectional diffusion in the Future. Divergences among M. laxiflora populations might have been induced by the drastic changes of the external environment and limited seed/pollen dispersal capacity, as the results of long-term ecological adaptability of summer flooding stress. The haplotypes of nuclear gene could be used for population's differentiation and germplasm protection. This identified gene flow and range dynamics have provided support for the gene-flow and geology hypothesis. It is also crucial for rescuing conservation to understand the impact of environmental dynamics on endangered organism evolution.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Is It Safe for Me to Get It? Factors Influencing COVID-19 Vaccination Decision-Making among Postpartum Women Who Are Black and Hispanic in Deep South.

BACKGROUND: COVID-19 vaccination is vital for ending the pandemic, yet safety concerns persist among pregnant and postpartum women, especially those who are Black and Hispanic. This study aims to explore factors that influence postpartum women's vaccination decision-making during pregnancy and postpartum through women's lived experiences and maternal care providers' (MCPs) observations. METHODS: From January to August 2022, we conducted semi-structured interviews with postpartum women who are Black and Hispanic and with MCPs. Participants were recruited from obstetric and pediatric clinics in South Carolina and had given birth in 2021. Thematic analysis was employed for data analysis. RESULTS: The study involved 19 Black and 20 Hispanic women, along with 9 MCPs, and revealed both barriers and facilitators to COVID-19 vaccination. The factors that influence pregnant and postpartum women's decision about COVID-19 vaccine uptake included: 1) awareness of health threats associated with COVID-19 vaccines, 2) vaccine availability and accessibility, 3) vaccine-related knowledge and exposure to misinformation, 4) concerns regarding pre-existing health conditions and potential side effects of COVID-19 vaccines, 5) emotional factors associated with vaccination decision-making processes, 6) concerns about the well-being of infants, 7) cultural perspectives, and 8) encouragement by trusted supporters. CONCLUSION: The findings suggest that reliable information, social support, and trusted MCPs' advice can motivate COVID-19 vaccination among pregnant and postpartum women who are Black and Hispanic. However, barriers such as misinformation, mistrust in the health care system, and fears of potential side effects impede vaccination uptake. Future interventions should address these barriers, consider health disparities, involve trusted MCPs, and initiate conversations about vaccines to promote vaccination among these populations.