bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health and economic outcomes of a universal early intervention for parents and children from birth to age five: evaluation of the Salut Programme using a natural experiment
Authors: Sampaio Filipa , Häggström Jenny , Ssegonja Richard , Eurenius Eva , Ivarsson Anneli , Pulkki-Brännström Anni-Maria , Feldman Inna 
Published: May 2023

Abstract
Background
The aim of this study was to investigate the health and economic outcomes of a universal early intervention for parents and children, the Salut Programme, from birth to when the child completed five years of age.

Methods
This study adopted a retrospective observational design using routinely collected linked register data with respect to both exposures and outcomes from Västerbotten county, in northern Sweden. Making use of a natural experiment, areas that received care-as-usual (non-Salut area) were compared to areas where the Programme was implemented after 2006 (Salut area) in terms of: (i) health outcomes, healthcare resource use and costs around pregnancy, delivery and birth, and (ii) healthcare resource use and related costs, as well as costs of care of sick child. We estimated total cumulative costs related to inpatient and specialised outpatient care for mothers and children, and financial benefits paid to mothers to stay home from work to care for a sick child. Two analyses were conducted: a matched difference-in difference analysis using the total sample and an analysis including a longitudinal subsample.

Results
The longitudinal analysis on mothers who gave birth in both pre- and post-measure periods showed that mothers exposed to the Programme had on average 6% (95% CI 3–9%) more full-term pregnancies and 2% (95% CI 0.03-3%) more babies with a birth weight ≥ 2500 g, compared to mothers who had care-as-usual. Savings were incurred in terms of outpatient care costs for children of mothers in the Salut area ($826). The difference-in-difference analysis using the total sample did not result in any significant differences in health outcomes or cumulative resource use over time.

Conclusions
The Salut Programme achieved health gains, as a health promotion early intervention for children and parents, in terms of more full-term pregnancies and more babies with a birth weight ≥ 2500 g, at reasonable cost, and may lead to lower usage of outpatient care. Other indicators point towards positive effects, but the small sample size may have led to underestimation of true differences.
Inadequate receipt of ANC components and associated factors among pregnant women in Northwest Ethiopia, 2020–2021: a community-based cross-sectional study
Authors: Gelagay Abebaw Addis , Belachew Tadele Biresaw , Asmamaw Desale Bihonegn , Bitew Desalegn Anmut , Fentie Elsa Awoke , Worku Abebaw Gebeyehu , Bashah Debrework Tesgera , Tebeje Nigusie Birhan , Gebrie Mignote Hailu , Yeshita Hedija Yenus , Cherkose Endeshaw Adimasu , Ayana Birhanu Abera , Lakew Ayenew Molla , Negash Wubshet Debebe 
Published: May 2023

Abstract
Background
Women's health and pregnancy outcomes are directly depends on the extent of ANC components received during their ANC visits. There are limited information about the components of ANC and associated factors. Therefore, the aim of this study was to assess the magnitude of inadequate recipient of ANC components and associated factors in northwest Ethiopia.

Methods
This is a community based cross sectional survey conducted in Dabat Demographic and health survey from December 10/2020 to January 10/2021 among women who gave birth within two years before the survey. This study applied a census method to identify and select eligible pregnant women. A structured and pretested questionnaire was used to collect the data. The data was entered into Epi-data version 3.1 and exported to STATA version 14 for analysis purpose. Adjusted Odds Ratio at 95% confidence interval was used to show the association between dependent and independent variables. Statistical significance was declared at a P value less than 0.05.

Results
A total of 871 pregnant women were identified from the survey and included in this study. Overall, 96.67% (95% CI: 95.24, 97.67) had not get adequate (all components) ANC. The components of ANC services were increased from 3.35 to 32.34%, 2.52 to 46.33% 1.96 to 55.8%, 2.31 to 46.53%, 3.54 to 55.75%, 2.46 to 44.62%, 1.18 to 45.96%, and 2.45 to 54.6% for tetanus toxoid Vaccine, HIV/AIDS testing and counseling, danger sign, place of delivery, deworming, iron folic acid, family planning, and breast feeding counseling, from first ANC visit to fourth ANC visit, respectively. Rural residence (AOR = 4.89, 95% CI: 1.21, 19.86), and less than four number of ANC visit (AOR = 5.15, 95% CI: 2.06, 12.86) were significantly associated with inadequate uptake of ANC components.

Conclusion
Only three in hundred pregnant women were received adequate ANC components in the study area. Rural residence and less than four number of ANC visit were factors significantly associated with inadequate ANC uptake. Therefore, the district health department managers and program implementers need to train the health care providers about the components of ANC. As well, increasing community and facility awareness of WHO recommendations on ANC visits focusing on rural women is needed.
Echinomycin as a promising therapeutic agent against KSHV-related malignancies
Authors: Chen Jungang , Lin Zhen , Song Jiao , Plaisance-Bonstaff Karlie , James Jennifer , Mu Shengyu , Post Steven R. , Dai Lu , Qin Zhiqiang 
Published: May 2023

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, through simultaneously inhibiting Myc and HIF1α expression. Echinomycin treatment also induces viral lytic gene expression whereas not increasing infectious virions production from KSHV + tumor cells. Our comparative transcriptomic analysis has identified a bunch of new Echinomycin-regulated, Myc- and HIF1α-related genes contributed to KSHV pathogenesis, including KDM4B and Tau, which are required for the survival of KSHV + tumor cells with functional validation. These data together reveal that dual targeting Myc and HIF1α such as using Echinomycin may represent a new and promising option for treatments of these virus-associated malignancies.
Boosting the epoxidation of squalene to produce triterpenoids in Saccharomyces cerevisiae
Authors: Du Meng-Meng , Zhang Ge-Ge , Zhu Zhan-Tao , Zhao Yun-Qiu , Gao Bei , Tao Xin-Yi , Wang Feng-Qing , Wei Dong-Zhi 
Published: May 2023

AbstractBackgroundPolycyclic triterpenoids (PTs) are common in plants, and have attracted considerable interest due to their remarkable biological activities. Currently, engineering the ergosterol synthesis pathway inSaccharomyces cerevisiaeis a safe and cost-competitive way to produce triterpenoids. However, the strict regulation of ERG1 involved in the epoxidation of squalene limits the triterpenoid production.ResultsIn this study, we found that the decrease in ERG7 protein level could dramatically boost the epoxidation of squalene by improving the protein stability of ERG1. We next explored the potential factors that affected the degradation process of ERG1 and confirmed that ERG7 was involved in the degradation process of ERG1. Subsequently, expression of four different triterpene cyclases utilizing either 2,3-oxidosqualene or 2,3:22,23-dioxidosqualene as the substrate in ERG7-degraded strains showed that the degradation of ERG7 to prompt the epoxidation of squalene could significantly increase triterpenoid production. To better display the potential of the strategy, we increased the supply of 2,3-oxidosqualene, optimized flux distribution between ergosterol synthesis pathway and β-amyrin synthesis pathway, and modified the GAL-regulation system to separate the growth stage from the production stage. The best-performing strain ultimately produced 4216.6 ± 68.4 mg/L of β-amyrin in a two-stage fed-fermentation (a 47-fold improvement over the initial strain).ConclusionsThis study showed that deregulation of the native restriction in ergosterol pathway was an effective strategy to increase triterpenoid production in yeast, which provided a new insight into triterpenoids biosynthesis.
Urticaria after breakthrough Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 infection in a triple-vaccinated (Pfizer) patient: a case report
Authors: Ciuoderis Karl , Perez Laura , Alvarez Catalina , Usuga Jaime , Carvajal Leidi , Cardona Andrés , Maya Maria A. , Cloherty Gavin , Hernandez-Ortiz Juan P. , Osorio Jorge E. 
Published: May 2023

Abstract
Background
Severe acute respiratory syndrome coronavirus 2 continues to threaten public health. The virus is causing breakthrough infections in vaccinated individuals. Also, scarce information is available about cutaneous manifestations after severe acute respiratory syndrome coronavirus 2 infection.

Case presentation and findings
A case of a triple-vaccinated (Pfizer) 37-year-old Hispanic American (Colombian) male who developed urticaria after Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 breakthrough infection is described. Virus isolation and whole genome sequencing along with immune and molecular assays were performed. Dermatological manifestations (skin rash and urticaria) after Omicron BA.5.1 infection were observed. Sequence analysis of the Omicron BA.5.1 isolate also revealed several important mutations. Hemogram analysis revealed leukocytosis and neutrophilia. Serology testing revealed anti-spike immunoglobulin G serum titers but negative detection of immunoglobulin M at 10 days after symptom onset. Anti-nucleocapsid, anti-spike 1 immunoglobulin G, anti-spike trimer, and anti-receptor-binding-domain immunoglobulin G and immunoglobulin E sera were detected at different titers 10 days after symptom onset. Several serum levels of chemokines/cytokines (Interferon-α, interferon-γ, interleukin-12/interleukin-23p40, interleukin-18, interferon gamma-induced protein-10, monocyte chemoattractant protein-1, monokine induced by gamma, macrophage inflammatory protein-1α, chemokine (C-C motif) ligand-5 , tumor necrosis factor-β1, Tumor necrosis factor-α) were detected, but interleukin-2, interleukin-4, interleukin-6, interleukin-8, and interleukin-17A were below the limit of detection.

Interpretation and conclusions
To our knowledge, this is the first study describing skin effects of a severe acute respiratory syndrome coronavirus 2 Omicron BA.5 variant breakthrough infection in a triple-vaccinated patient in Colombia. Several important mutations were found in the spike glycoprotein of the virus isolated; these mutations are associated with immune evasion and changes in antigenic properties of the virus. Physicians overseeing coronavirus disease 2019 cases should be aware of the potential skin effects of the infection. Pathogenesis of severe acute respiratory syndrome coronavirus 2 infection and its association with proinflammatory cytokines and chemokines may enhance the development of urticaria and other skin manifestations in immunized individuals. However, further studies are needed to better understand the complexity of coronavirus disease in such situations.
TMT-based quantitative proteomic analysis of spheroid cells of endometrial cancer possessing cancer stem cell properties
Authors: Cao Mingzhu , Liu Zhi , You Danming , Pan Yingying , Zhang Qingyan 
Published: May 2023

Abstract
Background
Cancer stem cells (CSCs) play an important role in endometrial cancer progression and it is potential to isolate CSCs from spheroid cells. Further understanding of spheroid cells at protein level would help find novel CSC markers.

Methods
Spheroid cells from endometrial cancer cell lines, Ishikawa and HEC1A, exhibited increased colony forming, subsphere forming, chemo-drug resistance, migration, invasion ability and tumorigenicity, verifying their cancer stem-like cell properties. The up-regulated CD90, CD117, CD133 and W5C5 expression also indicated stemness of spheroid cells. TMT-based quantitative proteomic analysis was performed to explore the potential alterations between parent cells and cancer stem-like spheroid cells. HK2-siRNA was transfected to Ishikawa and HEC1A cells to explore the roles and molecular mechanism of HK2 in endometrial cancer.

Results
We identified and quantified a total of 5735 proteins and 167 overlapped differentially expressed proteins of two cell types, 43 proteins were up-regulated and 124 were down-regulated in spheroid cells comparing with parent cells. KEGG pathway revealed a significant role of HIF-1 pathway in spheroid cells. qRT-PCR and western blot results of GPRC5A, PFKFB3 and HK2 of HIF-1 pathway confirmed their elevated expressions in spheroid cells which were consistent with proteomic results. HK2 promoted cancer stemness in endometrial cancer.

Conclusion
These findings indicate that spheroid cells from endometrial cancer cell lines possess cancer stem-like cell properties and enrich CSCs. HIF-1 pathway is activated in endometrial cancer stem-like spheroid cells.
Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson’s disease
Authors: Constantin Ioana Medeleine , Voruz Philippe , Péron Julie Anne 
Published: May 2023

Abstract
Background
Non-motor symptoms are an important early feature of Parkinson’s disease (PD), encompassing a variety of cognitive and psychiatric symptoms that seem to manifest differently depending on motor symptom asymmetry. Different factors, such as uric acid (UA) and sex, seem to influence cognitive and psychiatric expression in PD, however their interplay remains to be better understood.

Methods
Participants taking part in the Parkinson’s Progression Marker Initiative were studied based on the side of motor symptom asymmetry and sex. Three-way interaction modeling was used to examine the moderating effects of sex and UA on cognitive functions and psychiatric symptoms.

Results
Significant three-way interactions were highlighted at 1-year follow-up between motor symptom asymmetry, UA and sex for immediate and long-term memory in female patients exhibiting predominantly left-sided motor symptoms, and for processing speed and sleepiness in female patients exhibiting predominantly right-sided motor symptoms. No significant interactions were observed for male patients. Moreover, female patients exhibiting predominantly right-sided motor symptoms demonstrated lower serum UA concentrations and had overall better outcomes, while male patients with predominantly right-sided motor symptoms demonstrated particularly poor outcomes.

Conclusions
These findings suggest that in the earliest stages of the disease, UA and sex moderate cognitive functions and psychiatric symptoms differently depending on motor asymmetry, holding important clinical implications for symptom management in patients.
School-based Psychosocial interventions on mental health among Chinese rural children with traumatic experiences: a protocol using cluster randomized controlled trial
Authors: Guo Jing , Liu Xiaohan , Huang Ning , Yang Fan , Bai Yashuang , Zhang Bo , Lodder Paul 
Published: May 2023

Abstract
Background
The first aim of this study is to test the effectiveness of school-based psychosocial interventions for improving mental health in rural Chinese children with traumatic experiences. The second aim is to examine which individual, family and school related factors could explain the effectiveness of school-based psychosocial interventions. Third, we will investigate whether individual, family, and school related conditions play a moderator role on the effectiveness of school-based psychosocial interventions.

Methods
This study will conduct a cluster randomized controlled trial (RCT) in a large sample of Chinese rural children. Four rural counties in Shandong (Central China), Henan (Central China), Inner Mongolia (Northern China), and Xinjiang (Western China) will be selected as study settings from which schools will be sampled. Each sampled school will be randomly allocated either the intervention groups or a control group. Randomization will be performed by the research member who is not involved in the intervention stage. In each school students in grade 5 or higher will be recruited to ensure that approximately 50 children aged 10 to 18 years will be included. In each county, one high school, one middle school, and one primary school will be randomly chosen as the intervention group, and the other three similar schools will be chosen as control (waiting list) groups. A standardized and uniform research protocol will be applied in all intervention schools. All school social workers and psychological teachers would receive one week of in-person training following procedures. School-based psychosocial interventions included 14 group sessions for 14 consecutive weeks.

Discussion
This study would develop school-based mental health promotion policy recommendations to improve Chinese rural children’s mental health. This study can provide solid evidence for the promotion of school-based intervention in general.

Trial registration
ChiCTR2300069405, Registered on 15 March 2023.
Performance and safety effectiveness evaluation of mini-roundabouts in Michigan
Authors: Qawasmeh Baraah , Kwigizile Valerian , Oh Jun-Seok 
Published: May 2023

AbstractThis study evaluates the performance and safety effectiveness of mini-roundabouts. Crash, operational, and geometric data for 14 mini-roundabouts located in the state of Michigan were collected for both before and after installation time periods between 2007 and 2016. Three years of complete before and after installation crash data were analyzed utilizing the Before-and-After study with Comparison Group methodology. A total 28 untreated sites with similar characteristics to the 14 mini-roundabouts sites were used to account for changes in crashes unrelated to the treatment (mini-roundabout installation), evaluate the impacts of the treatment on the intersection, and develop the crash modification factors (CMFs). The results for overall safety effectiveness indicate a decrease in total crashes at signalized intersections when converted into mini-roundabouts, and an increase in total crashes at two-way stop-controlled (TWSC) and all-way stop-controlled (AWSC) intersections when converted into mini-roundabouts. The recommended CMFs for converting a TWSC, AWSC, and signalized intersection into a mini-roundabout are 1.039, 1.051, and 0.755 for total crashes, respectively.
Cyclin-Dependent Kinase 4/6 Inhibitors Beyond Progression in Metastatic Breast Cancer: A Retrospective Real-World Biomarker Analysis
Authors: Gerratana Lorenzo , Davis Andrew A. , Velimirovic Marko , Reduzzi Carolina , Clifton Katherine , Bucheit Leslie , Hensing Whitney L. , Shah Ami N. , Pivetta Tania , Dai Charles S. , D'Amico Paolo , Wehbe Firas , Medford Arielle , Wander Seth A. , Gradishar William J. , Behdad Amir , Ma Cynthia X. , Puglisi Fabio , Bardia Aditya , Cristofanilli Massimo 
Published: May 2023

PURPOSE As the continuation beyond progression (BP) of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is becoming increasingly attractive for the treatment of patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer (MBC), the definition of resistance factors is crucial. The aim of the study was to investigate the impact of CDK 4/6i BP and to explore potential genomic stratification factors. MATERIALS AND METHODS We retrospectively analyzed a multi-institutional cohort of patients with HR-positive HER2-negative MBC characterized for circulating tumor DNA through next-generation sequencing before treatment start. Differences across subgroups were analyzed by chi-square test, and survival was tested by univariable and multivariable Cox regression. Further correction was applied by propensity score matching. RESULTS Among the 214 patients previously exposed to CDK4/6i, 172 were treated with non–CDK4/6i-based treatment (non-CDK) and 42 with CDK4/6i BP. Multivariable analysis showed a significant impact of CDK4/6i BP, TP53 single-nucleotide variants, liver involvement, and treatment line on both progression-free survival (PFS) and overall survival (OS). Propensity score matching confirmed the prognostic role of CDK4/6i BP both for PFS and OS. The favorable impact of CDK4/6i BP was consistent across all subgroups, and a differential benefit was suggested for ESR1-mutated patients. ESR1 and RB1 mutations were more represented in the CDK4/6i BP subgroup with respect to CDK4/6i upfront. CONCLUSION The study highlighted a significant prognostic impact of the CDK4/6i BP strategy with a potential added benefit in patients with ESR1 mutations suggesting the need for an extensive biomarker characterization.
Fibroblast Growth Factor 23, Glucose Homeostasis, and Incident Diabetes: Findings of 2 Cohort Studies
Authors: van der Vaart Amarens , Eelderink Coby , van Beek André P , Bakker Stephan J L , van Dijk Peter R , de Borst Martin H 
Published: May 2023

Abstract

Context
The phosphate-regulating hormone fibroblast growth factor 23 (FGF23) has been linked to deregulations in glucose metabolism, but its role is insufficiently understood.

Objective
This study investigates potential crosstalk between FGF23 and glucose homeostasis.

Methods
First, we investigated the effect of glucose loading on plasma C-terminal FGF23 levels and its temporal relationship with changes in plasma phosphate in 45 overweight (body mass index [BMI] 25-30) individuals using time-lag analyses. Second, we studied cross-sectional associations of plasma C-terminal FGF23 levels with glucose homeostasis using multivariable linear regression in a population-based cohort. We also investigated associations of FGF23 with incident diabetes and obesity (BMI &gt; 30) in individuals without diabetes or obesity at baseline, respectively, using multivariable Cox regression analyses. Finally, we explored whether the association between FGF23 and diabetes depends on BMI.

Results
After glucose loading, changes in FGF23 preceded changes in plasma phosphate (Ptime-lag = .04). In the population-based cohort (N = 5482; mean age 52 years, 52% women, median FGF23 69 RU/mL), FGF23 was associated with plasma glucose (β = .13 [.03-.23]; P = .01), insulin (β = .10 [.03-.17]; P &lt; .001), and proinsulin (β = .06 [0.02-0.10]; P = .01) at baseline. On longitudinal analyses, a higher baseline FGF23 was independently associated with development of diabetes (199 events [4%]; fully adjusted hazard ratio [HR] 1.66 [95% CI, 1.06-2.60]; P = .03) and development of obesity (241 events [6%]; fully adjusted HR 1.84 [95% CI, 1.34-2.50]; P &lt; .001). The association between FGF23 and incident diabetes lost significance after additional adjustment for BMI.

Conclusion
Glucose loading has phosphate-independent effects on FGF23 and, vice versa, FGF23 is associated with glucose, insulin and proinsulin levels, and obesity. These findings suggest crosstalk between FGF23 and glucose homeostasis, which may promote susceptibility to incident diabetes.