bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge and attitude of spouses of puerperas towards breastfeeding
Authors: Yuan Zhan-Wang , Ma Li , Chen Yu-Ling , Ge Wen-Li , Zhao Hong , Du Yun , Li Xiu-Xiu 
Published: May 2024

Abstract
Objective
To investigate the extent of knowledge about breastfeeding and attitudes towards infant feeding among spouses of puerperas at the time of discharge from hospital, and explore the factors influencing spousal attitudes toward breastfeeding.

Methods
We conducted a questionnaire survey among 204 spouses of puerperas who were admitted in the maternity wards at a tertiary hospital in Shaanxi Province between October 2021 and December 2021. Respondents who fulfilled the inclusion criteria were identified using convenient sampling.

Results
(1) The score of breastfeeding knowledge among spouses prior to discharge from the hospital was (10.56 ± 3.78), with an accuracy rate of 59.6%, and the lowest accuracy rate was for Item 1 “Newborns should be fed on time, not on demand” (42.6%) and Item 5 “Breastfeeding can prevent infant rickets” (49.5%). (2) The average score of spouses’ infant feeding attitudes was (58.15 ± 5.55), and the lowest scoring was for Item 17 “Daily urine volume of infants is a reliable indicator to judge whether they get enough breast milk” (1.99 ± 1.14). (3) Generalized linear model analysis showed a more positive attitude (higher score) among spousal attitudes towards infant feeding in those who had received breastfeeding education [OR = 4.588, 95% CI (0.160 ∼ 3.598)] and those with a master’s degree or above [OR = 18.278, 95% CI (3.471 ∼ 9.346)].

Conclusion
(1) Spouses that received breastfeeding education and those that had a Masters Degree and above had more positive attitude towards infant feeding. (2) Medical staff should focus on puerperas’spouses with degrees below master’s level who had not received breastfeeding education. We recommend using a variety of education methods to enable them to acquire more knowledge on breastfeeding and develop a more positive attitude towards breastfeeding, which will further enhance spousal support for breastfeeding, thus positivizing postpartum co-parenting attitudes and improving the rate of exclusive breastfeeding.
The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study
Authors: Ghanbari Parisa , Raiesi Davoud , Alboebadi Roghayeh , Zarejavid Ahmad , Dianati Mostafa , Razmi Hamidreza , Bazyar Hadi 
Published: May 2024

Abstract
Background
Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD.

Methods
In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520 mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention.

Results
The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-β and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002).

Conclusions
It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients.

Trial Registration
The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413. (The registration date: 30/03/2022)
Nurturing transformative local structures of multisectoral collaboration for primary health care: qualitative insights from select states in India
Authors: Singh Shalini , Miller Emily , Closser Svea 
Published: May 2024

Abstract
Background
Multisectoral collaboration is essential for advancing primary health care (PHC). In low- and middle-income countries (LMICs), limited institutional capacities, governance issues, and inadequate stakeholder engagement impede multisectoral collaboration. India faces similar challenges, especially at the meso-level (districts and subdistricts). Owing to its dependence on context, and insufficient evidence, understanding “How” to improve multisectoral collaboration remains challenging. This study aims to elicit specific recommendations to strengthen meso-level stewardship in India for multisectoral collaboration. The findings from this study may offer lessons for other LMICs.

Methods
Using purposive, maximum variation sampling, the study team conducted semi-structured interviews with 20 diverse participants, including policymakers, implementers, development agency representatives, and academics experienced in multisectoral initiatives. The interviews delved into participants’ experiences, the current situation, enablers, and recommendations for enhancing stakeholder engagement and capacities at the meso-level for multisectoral collaboration.

Results
Context and power are critical elements to consider in fostering effective collaboration. Multisectoral collaboration was particularly successful in three distinct governance contexts: the social-democratic context as in Kerala, the social governance context in Chhattisgarh, and the public health governance context in Tamil Nadu. Adequate health system input and timely guidance instil confidence among local implementers to collaborate. While power plays a role through local leadership’s influence in setting agendas, convening stakeholders, and ensuring accountability. To nurture transformative local leaders for collaboration, holistic, equity-driven, community-informed approaches are essential. The study participants proposed several concrete steps: at the state level, establish “central management units” for supervising local implementers and ensuring bottom-up feedback; at the district level, rationalise committees and assign deliverables to stakeholders; and at the block level, expand convergence structures and involve local self-governments. Development partners can support data-driven priority setting, but local implementers with contextual familiarity should develop decentralised plans collaboratively, articulating rationales, activities, and resources. Finally, innovative training programs are required at all levels, fostering humility, motivation, equity awareness, leadership, problem- solving, and data use proficiency.

Conclusion
This study offers multiple solutions to enhance local implementers’ engagement in multisectoral efforts, advocating for the development, piloting, and evaluation of innovative approaches such as the block convergence model, locally-led collaboration efforts, and novel training methods for local implementers.
Generalizability of polygenic prediction models: how is the R2 defined on test data?
Authors: Staerk Christian , Klinkhammer Hannah , Wistuba Tobias , Maj Carlo , Mayr Andreas 
Published: May 2024

Abstract
Background
Polygenic risk scores (PRS) quantify an individual’s genetic predisposition for different traits and are expected to play an increasingly important role in personalized medicine. A crucial challenge in clinical practice is the generalizability and transferability of PRS models to populations with different ancestries. When assessing the generalizability of PRS models for continuous traits, the $$R^2$$

R
2

is a commonly used measure to evaluate prediction accuracy. While the $$R^2$$

R
2

is a well-defined goodness-of-fit measure for statistical linear models, there exist different definitions for its application on test data, which complicates interpretation and comparison of results.

Methods
Based on large-scale genotype data from the UK Biobank, we compare three definitions of the $$R^2$$

R
2

on test data for evaluating the generalizability of PRS models to different populations. Polygenic models for several phenotypes, including height, BMI and lipoprotein A, are derived based on training data with European ancestry using state-of-the-art regression methods and are evaluated on various test populations with different ancestries.

Results
Our analysis shows that the choice of the $$R^2$$

R
2

definition can lead to considerably different results on test data, making the comparison of $$R^2$$

R
2

values from the literature problematic. While the definition as the squared correlation between predicted and observed phenotypes solely addresses the discriminative performance and always yields values between 0 and 1, definitions of the $$R^2$$

R
2

based on the mean squared prediction error (MSPE) with reference to intercept-only models assess both discrimination and calibration. These MSPE-based definitions can yield negative values indicating miscalibrated predictions for out-of-target populations. We argue that the choice of the most appropriate definition depends on the aim of PRS analysis — whether it primarily serves for risk stratification or also for individual phenotype prediction. Moreover, both correlation-based and MSPE-based definitions of $$R^2$$

R
2

can provide valuable complementary information.

Conclusions
Awareness of the different definitions of the $$R^2$$

R
2

on test data is necessary to facilitate the reporting and interpretation of results on PRS generalizability. It is recommended to explicitly state which definition was used when reporting $$R^2$$

R
2

values on test data. Further research is warranted to develop and evaluate well-calibrated polygenic models for diverse populations.
Intelligent nanovesicle for remodeling tumor microenvironment and circulating tumor chemoimmunotherapy amplification
Authors: Huai Manxiu , Wang Yingjie , Li Junhao , Pan Jiaxing , Sun Fang , Zhang Feiyu , Zhang Yi , Xu Leiming 
Published: May 2024

AbstractImperceptible examination and unideal treatment effect are still intractable difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). At present, despite 5-fluorouracil (5-FU), as a clinical first-line FOLFIRINOX chemo-drug, has achieved significant therapeutic effects. Nevertheless, these unavoidable factors such as low solubility, lack of biological specificity and easy to induce immunosuppressive surroundings formation, severely limit their treatment in PDAC. As an important source of energy for many tumor cells, tryptophan (Trp), is easily degraded to kynurenine (Kyn) by indolamine 2,3- dioxygenase 1 (IDO1), which activates the axis of Kyn-AHR to form special suppressive immune microenvironment that promotes tumor growth and metastasis. However, our research findings that 5-FU can induce effectively immunogenic cell death (ICD) to further treat tumor by activating immune systems, while the secretion of interferon-γ (IFN-γ) re-induce the Kyn-AHR axis activation, leading to poor treatment efficiency. Therefore, a metal matrix protease-2 (MMP-2) and endogenous GSH dual-responsive liposomal-based nanovesicle, co-loading with 5-FU (anti-cancer drug) and NLG919 (IDO1 inhibitor), was constructed (named as ENP919@5-FU). The multifunctional ENP919@5-FU can effectively reshape the tumor immunosuppression microenvironment to enhance the effect of chemoimmunotherapy, thereby effectively inhibiting cancer growth. Mechanistically, PDAC with high expression of MMP-2 will propel the as-prepared nanovesicle to dwell in tumor region via shedding PEG on the nanovesicle surface, effectively enhancing tumor uptake. Subsequently, the S-S bond containing nanovesicle was cut via high endogenous GSH, leading to the continued release of 5-FU and NLG919, thereby enabling circulating chemoimmunotherapy to effectively cause tumor ablation. Moreover, the combination of ENP919@5-FU and PD-L1 antibody (αPD-L1) showed a synergistic anti-tumor effect on the PDAC model with abdominal cavity metastasis. Collectively, ENP919@5-FU nanovesicle, as a PDAC treatment strategy, showed excellent antitumor efficacy by remodeling tumor microenvironment to circulate tumor chemoimmunotherapy amplification, which has promising potential in a precision medicine approach.
The impact of the COVID-19 pandemic on people who use drugs in three Canadian cities: a cross-sectional analysis
Authors: Mitra Sanjana , Bouck Zachary , Larney Sarah , Zolopa Camille , Høj Stine , Minoyan Nanor , Upham Katie , Rammohan Indhu , Mok Wing Yin , Hayashi Kanna , Milloy M-J , DeBeck Kora , Scheim Ayden , Werb Dan 
Published: May 2024

Abstract
Background
The COVID-19 pandemic had a disproportionate impact on the health and wellbeing of people who use drugs (PWUD) in Canada. However less is known about jurisdictional commonalities and differences in COVID-19 exposure and impacts of pandemic-related restrictions on competing health and social risks among PWUD living in large urban centres.

Methods
Between May 2020 and March 2021, leveraging infrastructure from ongoing cohorts of PWUD, we surveyed 1,025 participants from Vancouver (n = 640), Toronto (n = 158), and Montreal (n = 227), Canada to describe the impacts of pandemic-related restrictions on basic, health, and harm reduction needs.

Results
Among participants, awareness of COVID-19 protective measures was high; however, between 10 and 24% of participants in each city-specific sample reported being unable to self-isolate. Overall, 3–19% of participants reported experiencing homelessness after the onset of the pandemic, while 20–41% reported that they went hungry more often than usual. Furthermore, 8–33% of participants reported experiencing an overdose during the pandemic, though most indicated no change in overdose frequency compared the pre-pandemic period. Most participants receiving opioid agonist therapy in the past six months reported treatment continuity during the pandemic (87–93%), however, 32% and 22% of participants in Toronto and Montreal reported missing doses due to service disruptions. There were some reports of difficulty accessing supervised consumption sites in all three sites, and drug checking services in Vancouver.

Conclusion
Findings suggest PWUD in Canada experienced difficulties meeting essential needs and accessing some harm reduction services during the COVID-19 pandemic. These findings can inform preparedness planning for future public health emergencies.
Characteristics of built food environments associated with alternative protein food choices: a systematic review
Authors: Zaleskiewicz Hanna , Kulis Ewa , Siwa Maria , Szczuka Zofia , Banik Anna , Grossi Francesca , Chrysochou Polymeros , Nystrand Bjørn Tore , Perrea Toula , Samoggia Antonella , Xhelili Arlind , Krystallis Athanasios , Luszczynska Aleksandra 
Published: May 2024

Abstract
Background
This systematic review contributes to the understanding of the characteristics of built food environments that may be associated with choices of alternative protein foods (APF). Using the built food environment typology proposed by Downs et al., we investigated various environmental structures (e.g., supermarkets, other retailers, farmers’ markets, restaurants, schools, and online vendors) and the characteristics that may facilitate or hinder consumers’ choices. For example, facilitators and barriers may refer to the physical characteristics of environmental structures, food presentation practices, the organizational strategies or policies operating in the setting, or the actions that retailers or consumers engage in while selling, serving, choosing, trying, or purchasing APF in these environmental structures.

Methods
A systematic review (PROSPERO database preregistration; no. CRD42023388700) was conducted by searching 13 databases for peer-reviewed journals focusing on the fields of economics and business, agriculture, medical sciences, and social sciences. Data searches, coding, and quality evaluations were conducted by at least 2 researchers. A total of 31 papers (36 original studies) were included. The risk of bias was evaluated with the Joanna Briggs Institute quality evaluation tool, with 24 publications presenting low risk of bias.

Results
The findings indicate that perceived and actual availability facilitate consumers’ APF choices across a built food environment. Several barriers/facilitators were associated with APF choices in specific types of built food environments: the way food is presented in produce sections (supermarkets), consumer habits in terms of green and specialty shopping (grocery stores), and mismatches among retailer actions in regard to making APF available in one type of food environment structure (e-commerce) and consumers’ preferences for APF being available in other food environment structures (supermarkets, grocery stores). The effect of a barrier/facilitator may depend on the APF type; for example, social norms regarding masculinity were a barrier affecting plant-based APF choices in restaurants, but these norms were not a barrier affecting the choice of insect-based APF in restaurants.

Conclusions
Addressing barriers/facilitators identified in this review will help in developing environment-matching interventions that aim to make alternative proteins mainstream.

Trial registration
PROSPERO database registration: #CRD42023388700.
Endothelial EGLN3-PKM2 signaling induces the formation of acute astrocytic barrier to alleviate immune cell infiltration after subarachnoid hemorrhage
Authors: Duan Mingxu , Ru Xufang , Zhou Jiru , Li Yuanshu , Guo Peiwen , Kang Wenbo , Li Wenyan , Chen Zhi , Feng Hua , Chen Yujie 
Published: May 2024

Abstract
Background
Most subarachnoid hemorrhage (SAH) patients have no obvious hematoma lesions but exhibit blood–brain barrier dysfunction and vasogenic brain edema. However, there is a few days between blood‒brain barrier dysfunction and vasogenic brain edema. The present study sought to investigate whether this phenomenon is caused by endothelial injury induced by the acute astrocytic barrier, also known as the glial limitans.

Methods
Bioinformatics analyses of human endothelial cells and astrocytes under hypoxia were performed based on the GEO database. Wild-type, EGLN3 and PKM2 conditional knock-in mice were used to confirm glial limitan formation after SAH. Then, the effect of endothelial EGLN3-PKM2 signaling on temporal and spatial changes in glial limitans was evaluated in both in vivo and in vitro models of SAH.

Results
The data indicate that in the acute phase after SAH, astrocytes can form a temporary protective barrier, the glia limitans, around blood vessels that helps maintain barrier function and improve neurological prognosis. Molecular docking studies have shown that endothelial cells and astrocytes can promote glial limitans-based protection against early brain injury through EGLN3/PKM2 signaling and further activation of the PKC/ERK/MAPK signaling pathway in astrocytes after SAH.

Conclusion
Improving the ability to maintain glial limitans may be a new therapeutic strategy for improving the prognosis of SAH patients.
Targeted treatment in complex lymphatic anomaly: a case of synergistic efficacy of trametinib and sirolimus
Authors: Seront Emmanuel , Froidure Antoine , Revencu Nicole , Dekeuleneer Valerie , Clapuyt Philippe , Dumitriu Dana , Vikkula Miikka , Boon Laurence M. 
Published: May 2024

AbstractRepurposing anticancer drugs to vascular malformations has significantly improved patient outcomes. Complex Lymphatic Anomalies (CLA) are part of the spectrum of lymphatic malformations (LMs) that share similar oncogenic mutations to cancer. We report the case of a young patient with highly symptomatic CLA who was initially treated with sirolimus, due to the frequent involvement of the PI3K-AKT-mTOR pathway in CLA pathogenesis. Despite an initial reduction in symptoms, sirolimus progressively lost its effectiveness. After an unsuccessful attempt with trametinib alone, sirolimus was added to trametinib and resulted in a significant, rapid and sustained improvement in symptoms. This suggests that, contrary to current dogmas, combination therapy using sub-therapeutic doses targeting both the PI3K and RAS pathways retains efficacy without generating the toxicity known for combination therapies, and is beneficial in the management of CLAs and potentially other vascular anomalies.
Worldwide absence of canonical benzimidazole resistance-associated mutations within β-tubulin genes from Ascaris
Authors: Jones Ben P. , Kozel Kezia , Alonte Allen Jethro I. , Llanes Kennesa Klariz R. , Juhász Alexandra , Chaudhry Umer , Roose Sara , Geldhof Peter , Belizario Vicente Y. , Nejsum Peter , Stothard J. Russell , LaCourse E. James , van Vliet Arnoud H. M. , Paller Vachel Gay V. , Betson Martha 
Published: May 2024

Abstract
Background
The giant roundworm Ascaris is an intestinal nematode, causing ascariasis by infecting humans and pigs worldwide. Recent estimates suggest that Ascaris infects over half a billion people, with chronic infections leading to reduced growth and cognitive ability. Ascariasis affects innumerable pigs worldwide and is known to reduce production yields via decreased growth and condemnation of livers. The predominant anthelminthic drugs used to treat ascariasis are the benzimidazoles. Benzimidazoles interact with β-tubulins and block their function, and several benzimidazole resistance-associated mutations have been described in the β-tubulins of ruminant nematodes. Recent research on ascarids has shown that these canonical benzimidazole resistance-associated mutations are likely not present in the β-tubulins of Ascaris, Ascaridia or Parascaris, even in phenotypically resistant populations.

Methods
To further determine the putative absence of key β-tubulin polymorphisms, we screened two β-tubulin isotypes of Ascaris, highly expressed in adult worms. Using adult and egg samples of Ascaris obtained from pigs and humans worldwide, we performed deep amplicon sequencing to look for canonical resistance-associated mutations in Ascaris β-tubulins. Subsequently, we examined these data in closer detail to study the population dynamics of Ascaris and genetic diversity within the two isotypes and tested whether genotypes appeared to partition across human and pig hosts.

Results
In the 187 isolates, 69 genotypes were found, made up of eight haplotypes of β-tubulin isotype A and 20 haplotypes of isotype B. Single nucleotide polymorphisms were seen at 14 and 37 positions for β-tubulin isotype A and isotype B, respectively. No evidence of any canonical benzimidazole resistance-associated mutations was found in either human- or pig-derived Ascaris isolates. There was, however, a difference in the genetic diversity of each isotype and distribution of β-tubulin genotypes between human- and pig-derived Ascaris. Statistical tests of population differentiation show significant differences (p < 0.001) between pig- and human-derived worms; however, more diversity was seen between worms from different populations than worms from different hosts.

Conclusions
Our work suggests an absence of canonical β-tubulin mutations within Ascaris, but alternative modes of anthelminthic resistance may emerge necessitating continued genetic scrutiny alongside monitoring of drug efficacy.

Graphical Abstract