bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting social, emotional, and cognitive development in early childhood: A protocol for early valuation of a culturally adapted digital tool for supporting optimal childrearing practices
Authors: LaMonica Haley M , Song Yun J. C. , Loblay Victoria , Ekambareshwar Mahalakshmi , Naderbagi Aila , Zahed Iqthyer Uddin Md , Troy Jakelin , Hickie Ian B. 
Published: April 2024

Objective The Thrive by Five app promotes positive interactions between children and parents, extended family, and trusted community members that support optimal socio-emotional and cognitive development in the early years. This article aims to describe the protocol for a prospective mixed-methods multi-site study evaluating Thrive by Five using surveys, interviews, workshops, audio diaries from citizen ethnographers and app usage data. Methods The study activities and timelines differ by site, with an extensive longitudinal evaluation being conducted at two sites and a basic evaluation being conducted at five sites. The learnings from the more comprehensive evaluations inform the iterative research and development processes while also ensuring ongoing evaluation of usability, acceptability and effectiveness of the app and its content across varying contexts. The study evaluates: (1) the impact of the Thrive by Five content on caregiver knowledge, behaviours, attitudes and confidence; (2) how the content changes relationships at the familial, community and system level; (3) how cultural and contextual factors influence content engagement and effectiveness and (4) the processes that facilitate or disrupt the success of the implementation and dissemination. Results All in-country partners have been identified and data collection has been completed in Indonesia, Malaysia, Afghanistan, Kyrgyzstan, Uzbekistan, Namibia and Cameroon. Conclusions Very few digital health solutions have been trialled for usability and effectiveness in diverse cultural contexts. By combining quantitative, qualitative, process and ethnographic methodologies, this innovative study informs the iterative and ongoing optimisation of the cultural and contextual sensitivity of the Thrive by Five content and the processes supporting implementation and dissemination.
SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms
Authors: Wang Tairan , Jin Yan , Wang Mengyao , Chen Boya , Sun Jinyu , Zhang Jiaying , Yang Hui , Deng Xinyao , Cao Xingyue , Wang Lidong , Tang Yuanyuan 
Published: April 2024

AbstractEffective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.
Escaping from CRISPR–Cas-mediated knockout: the facts, mechanisms, and applications
Authors: Wang Ying , Zhai Yujing , Zhang Mingzhe , Song Chunlin , Zhang Yuqing , Zhang Gang 
Published: April 2024

AbstractClustered regularly interspaced short palindromic repeats and associated Cas protein (CRISPR–Cas), a powerful genome editing tool, has revolutionized gene function investigation and exhibits huge potential for clinical applications. CRISPR–Cas-mediated gene knockout has already become a routine method in research laboratories. However, in the last few years, accumulating evidences have demonstrated that genes knocked out by CRISPR–Cas may not be truly silenced. Functional residual proteins could be generated in such knockout organisms to compensate the putative loss of function, termed herein knockout escaping. In line with this, several CRISPR–Cas-mediated knockout screenings have discovered much less abnormal phenotypes than expected. How does knockout escaping happen and how often does it happen have not been systematically reviewed yet. Without knowing this, knockout results could easily be misinterpreted. In this review, we summarize these evidences and propose two main mechanisms allowing knockout escaping. To avoid the confusion caused by knockout escaping, several strategies are discussed as well as their advantages and disadvantages. On the other hand, knockout escaping also provides convenient tools for studying essential genes and treating monogenic disorders such as Duchenne muscular dystrophy, which are discussed in the end.
G6PD maintains the VSMC synthetic phenotype and accelerates vascular neointimal hyperplasia by inhibiting the VDAC1–Bax-mediated mitochondrial apoptosis pathway
Authors: Zhang Ting , Cao Rui-Jie , Niu Jiang-Ling , Chen Zhi-Huan , Mu Shi-Qing , Cao Tong , Pang Jie-Xin , Dong Li-Hua 
Published: April 2024

Abstract
Background
Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in vascular smooth muscle cell (VSMC) phenotypic switching, which is an early pathogenic event in various vascular remodeling diseases (VRDs). However, the underlying mechanism is not fully understood.

Methods
An IP‒LC‒MS/MS assay was conducted to identify new binding partners of G6PD involved in the regulation of VSMC phenotypic switching under platelet-derived growth factor-BB (PDGF-BB) stimulation. Co-IP, GST pull-down, and immunofluorescence colocalization were employed to clarify the interaction between G6PD and voltage-dependent anion-selective channel protein 1 (VDAC1). The molecular mechanisms involved were elucidated by examining the interaction between VDAC1 and apoptosis-related biomarkers, as well as the oligomerization state of VDAC1.

Results
The G6PD level was significantly elevated and positively correlated with the synthetic characteristics of VSMCs induced by PDGF-BB. We identified VDAC1 as a novel G6PD-interacting molecule essential for apoptosis. Specifically, the G6PD-NTD region was found to predominantly contribute to this interaction. G6PD promotes VSMC survival and accelerates vascular neointimal hyperplasia by inhibiting VSMC apoptosis. Mechanistically, G6PD interacts with VDAC1 upon stimulation with PDGF-BB. By competing with Bax for VDAC1 binding, G6PD reduces VDAC1 oligomerization and counteracts VDAC1–Bax-mediated apoptosis, thereby accelerating neointimal hyperplasia.

Conclusion
Our study showed that the G6PD–VDAC1–Bax axis is a vital switch in VSMC apoptosis and is essential for VSMC phenotypic switching and neointimal hyperplasia, providing mechanistic insight into early VRDs.

Graphical Abstract
Origin, evolution, and diversification of inositol 1,4,5-trisphosphate 3-kinases in plants and animals
Authors: Xiong Tao , Zhang Zaibao , Fan Tianyu , Ye Fan , Ye Ziyi 
Published: April 2024

Abstract
Background
In Eukaryotes, inositol polyphosphates (InsPs) represent a large family of secondary messengers and play crucial roes in various cellular processes. InsPs are synthesized through a series of pohophorylation reactions catalyzed by various InsP kinases in a sequential manner. Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP3K), one member of InsP kinase, plays important regulation roles in InsPs metabolism by specifically phosphorylating inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP4) in animal cells. IP3Ks were widespread in fungi, plants and animals. However, its evolutionary history and patterns have not been examined systematically.

Results
A total of 104 and 31 IP3K orthologues were identified across 57 plant genomes and 13 animal genomes, respectively. Phylogenetic analyses indicate that IP3K originated in the common ancestor before the divergence of fungi, plants and animals. In most plants and animals, IP3K maintained low-copy numbers suggesting functional conservation during plant and animal evolution. In Brassicaceae and vertebrate, IP3K underwent one and two duplication events, respectively, resulting in multiple gene copies. Whole-genome duplication (WGD) was the main mechanism for IP3K duplications, and the IP3K duplicates have experienced functional divergence. Finally, a hypothetical evolutionary model for the IP3K proteins is proposed based on phylogenetic theory.

Conclusion
Our study reveals the evolutionary history of IP3K proteins and guides the future functions of animal, plant, and fungal IP3K proteins.
Impacts of ABCG2 loss of function variant (p. Gln141Lys, c.421 C > A, rs2231142) on lipid levels and statin efficiency: a systematic review and meta-analysis
Authors: Liu Yang , Chen Yuan , Wei Baozhu , Li Hang , Peng Yuanyuan , Luo Zhi 
Published: April 2024

Abstract
Background
The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency.

Methods
PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023.

Results
Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals.

Conclusions
The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.
Segmentation of patients with small cell lung cancer into responders and non-responders using the optimal cross-validation technique
Authors: Majd Elham , Xing Li , Zhang Xuekui 
Published: April 2024

Abstract
Background
The timing of treating cancer patients is an essential factor in the efficacy of treatment. So, patients who will not respond to current therapy should receive a different treatment as early as possible. Machine learning models can be built to classify responders and nonresponders. Such classification models predict the probability of a patient being a responder. Most methods use a probability threshold of 0.5 to convert the probabilities into binary group membership. However, the cutoff of 0.5 is not always the optimal choice.

Methods
In this study, we propose a novel data-driven approach to select a better cutoff value based on the optimal cross-validation technique. To illustrate our novel method, we applied it to three clinical trial datasets of small-cell lung cancer patients. We used two different datasets to build a scoring system to segment patients. Then the models were applied to segment patients into the test data.

Results
We found that, in test data, the predicted responders and non-responders had significantly different long-term survival outcomes. Our proposed novel method segments patients better than the standard approach using a cutoff of 0.5. Comparing clinical outcomes of responders versus non-responders, our novel method had a p-value of 0.009 with a hazard ratio of 0.668 for grouping patients using the Cox proportion hazard model and a p-value of 0.011 using the accelerated failure time model which approved a significant difference between responders and non-responders. In contrast, the standard approach had a p-value of 0.194 with a hazard ratio of 0.823 using the Cox proportion hazard model and a p-value of 0.240 using the accelerated failure time model indicating the responders and non-responders do not differ significantly in survival.

Conclusion
In summary, our novel prediction method can successfully segment new patients into responders and non-responders. Clinicians can use our prediction to decide if a patient should receive a different treatment or stay with the current treatment.
Novel synergistic interactions between monolaurin, a mono-acyl glycerol and β lactam antibiotics against Staphylococcus aureus: an in vitro study
Authors: Ghany Shimaa Salah Hassan Abd El , Ibrahem Reham A. , EL-Gendy Ahmed Osama , El-Baky Rehab Mahmoud Abd , Mustafa Ahmad , Azmy Ahmed Farag 
Published: April 2024

Abstract
Background
A major worldwide health issue is the rising frequency of resistance of bacteria.Drug combinations are a winning strategy in fighting resistant bacteria and might help in protecting the existing drugs.Monolaurin is natural compound extracted from coconut oil and has a promising antimicrobial activity against Staphylococcus.aureus. This study aims to examine the efficacy of monolaurin both individually and in combination with β-lactam antibiotics against Staphylococcus aureus isolates.

Methods
Agar dilution method was used for determination of minimum inhibitory concentration (MIC) of monolaurin against S.aureus isolates. Scanning electron microscope (SEM) was used to detect morphological changes in S.aureus after treatment with monolaurin. Conventional and Real-time Polymerase chain reaction (RT-PCR) were performed to detect of beta-lactamase (blaZ) gene and its expressional levels after monolaurin treatment. Combination therapy of monolaurin and antibiotics was assessed through fractional inhibitory concentration and time-kill method.

Results
The antibacterial activity of monolaurin was assessed on 115 S.aureus isolates, the MIC of monolaurin were 250 to 2000 µg/ml. SEM showed cell elongation and swelling in the outer membrane of S.aureus in the prescence of 1xMIC of monolaurin. blaZ gene was found in 73.9% of S.aureus isolates. RT-PCR shows a significant decrease in of blaZ gene expression at 250 and 500 µg/ml of monolaurin. Synergistic effects were detected through FIC method and time killing curve. Combination therapy established a significant reduction on the MIC value. The collective findings from the antibiotic combinations with monolaurin indicated synergism rates ranging from 83.3% to 100%.In time-kill studies, combination of monolaurin and β-lactam antibiotics produced a synergistic effect.

Conclusion
This study showed that monolaurin may be a natural antibacterial agent against S. aureus, and may be an outstanding modulator of β-lactam drugs. The concurrent application of monolaurin and β-lactam antibiotics, exhibiting synergistic effects against S. aureus in vitro, holds promise as potential candidates for the development of combination therapies that target particularly, patients with bacterial infections that are nearly incurable.
Dynamic radiomics based on contrast-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma
Authors: Zhang Rui , Wang Yao , Li Zhi , Shi Yushu , Yu Danping , Huang Qiang , Chen Feng , Xiao Wenbo , Hong Yuan , Feng Zhan 
Published: April 2024

Abstract
Objective
To exploit the improved prediction performance based on dynamic contrast-enhanced (DCE) MRI by using dynamic radiomics for microvascular invasion (MVI) in hepatocellular carcinoma (HCC).

Methods
We retrospectively included 175 and 75 HCC patients who underwent preoperative DCE-MRI from September 2019 to August 2022 in institution 1 (development cohort) and institution 2 (validation cohort), respectively. Static radiomics features were extracted from the mask, arterial, portal venous, and equilibrium phase images and used to construct dynamic features. The static, dynamic, and dynamic–static radiomics (SR, DR, and DSR) signatures were separately constructed based on the feature selection method of LASSO and classification algorithm of logistic regression. The receiver operating characteristic (ROC) curves and the area under the curve (AUC) were plotted to evaluate and compare the predictive performance of each signature.

Results
In the three radiomics signatures, the DSR signature performed the best. The AUCs of the SR, DR, and DSR signatures in the training set were 0.750, 0.751 and 0.805, respectively, while in the external validation set, the corresponding AUCs were 0.706, 0756 and 0.777. The DSR signature showed significant improvement over the SR signature in predicting MVI status (training cohort: P = 0.019; validation cohort: P = 0.044). After external validation, the AUC value of the SR signature decreased from 0.750 to 0.706, while the AUC value of the DR signature did not show a decline (AUCs: 0.756 vs. 0.751).

Conclusions
The dynamic radiomics had an improved effect on the MVI prediction in HCC, compared with the static DCE MRI-based radiomics models.
Do tuition-free lower secondary education policies matter for antenatal care among women in sub-saharan African countries?
Authors: Bose Bijetri , Raub Amy , Sprague Aleta , Martin Alfredo , Bhuwania Pragya , Kidman Rachel , Heymann Jody 
Published: April 2024

Abstract
Background
Antenatal care (ANC) is critical to reducing maternal and infant mortality. However, sub-Saharan Africa (SSA) continues to have among the lowest levels of ANC receipt globally, with half of mothers not meeting the WHO minimum recommendation of at least four visits. Increasing ANC coverage will require not only directly reducing geographic and financial barriers to care but also addressing the social determinants of health that shape access. Among those with the greatest potential for impact is maternal education: past research has documented a relationship between higher educational attainment and antenatal healthcare access, as well as related outcomes like health literacy and autonomy in health decision-making. Yet little causal evidence exists about whether changing educational policies can improve ANC coverage. This study fills this research gap by investigating the impact of national-level policies that eliminate tuition fees for lower secondary education in SSA on the number of ANC visits.

Methods
To estimate the effect of women’s exposure to tuition-free education policies at the primary and lower secondary levels on their ANC visits, a difference-in-difference methodology was employed. This analysis leverages the variation in the timing of education policies across nine SSA countries.

Results
Exposure to tuition-free primary and lower secondary education is associated with improvements in the number of ANC visits, increasing the share of women meeting the WHO recommendation of at least four ANC visits by 6–14%. Moreover, the impact of both education policies combined is greater than that of tuition-free primary education alone. However, the effects vary across individual treatment countries, suggesting the need for further investigation into country-specific dynamics.

Conclusions
The findings of this study have significant implications for policymakers and stakeholders seeking to improve ANC coverage. Removing the tuition barrier at the secondary level has shown to be a powerful strategy for advancing health outcomes and educational attainment. As governments across Africa consider eliminating tuition fees at the secondary level, this study provides valuable evidence about the impacts on reproductive health outcomes. While investing in free education requires initial investment, the long-term benefits for both human development and economic growth far outweigh the costs.
Umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis
Authors: Watson Estelle D. , Roberts Lily F , Harding Jane E , Crowther Caroline A , Lin Luling 
Published: April 2024

Abstract
Background
Placental management strategies such as umbilical cord milking and delayed cord clamping may provide a range of benefits for the newborn. The aim of this review was to assess the effectiveness of umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia.

Methods
Three databases and five clinical trial registries were systematically reviewed to identify randomised controlled trials comparing umbilical cord milking or delayed cord clamping with control in term and preterm infants. The primary outcome was neonatal hypoglycaemia (study defined). Two independent reviewers conducted screening, data extraction and quality assessment. Quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB-2). Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis using a random effect model was done using Review Manager 5.4. The review was registered prospectively on PROSPERO (CRD42022356553).

Results
Data from 71 studies and 14 268 infants were included in this review; 22 (2 537 infants) compared umbilical cord milking with control, and 50 studies (11 731 infants) compared delayed with early cord clamping. For umbilical cord milking there were no data on neonatal hypoglycaemia, and no differences between groups for any of the secondary outcomes. We found no evidence that delayed cord clamping reduced the incidence of hypoglycaemia (6 studies, 444 infants, RR = 0.87, CI: 0.58 to 1.30, p = 0.49, I2 = 0%). Delayed cord clamping was associated with a 27% reduction in neonatal mortality (15 studies, 3 041 infants, RR = 0.73, CI: 0.55 to 0.98, p = 0.03, I2 = 0%). We found no evidence for the effect of delayed cord clamping for any of the other outcomes. The certainty of evidence was low for all outcomes.

Conclusion
We found no data for the effectiveness of umbilical cord milking on neonatal hypoglycaemia, and no evidence that delayed cord clamping reduced the incidence of hypoglycaemia, but the certainty of the evidence was low.