bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation abnormalities induced by advanced maternal age in villi prime a high-risk state for spontaneous abortion
Authors: Qin Meng , Chen Wei , Hua Lingyue , Meng Yan , Wang Jing , Li Hanna , Yang Rui , Yan Liying , Qiao Jie 
Published: March 2023

Abstract
Background
Advanced maternal age (AMA) has increased in many high-income countries in recent decades. AMA is generally associated with a higher risk of various pregnancy complications, and the underlying molecular mechanisms are largely unknown. In the current study, we profiled the DNA methylome of 24 human chorionic villi samples (CVSs) from early pregnancies in AMA and young maternal age (YMA), 11 CVSs from early spontaneous abortion (SA) cases using reduced representation bisulfite sequencing (RRBS), and the transcriptome of 10 CVSs from AMA and YMA pregnancies with mRNA sequencing(mRNA-seq). Single-cell villous transcriptional atlas presented expression patterns of targeted AMA-/SA-related genes. Trophoblast cellular impairment was investigated through the knockdown of GNE expression in HTR8-S/Vneo cells.

Results
AMA-induced local DNA methylation changes, defined as AMA-related differentially methylated regions (DMRs), may be derived from the abnormal expression of genes involved in DNA demethylation, such as GADD45B. These DNA methylation changes were significantly enriched in the processes involved in NOTCH signaling and extracellular matrix organization and were reflected in the transcriptional alterations in the corresponding biological processes and specific genes. Furthermore, the DNA methylation level of special AMA-related DMRs not only significantly changed in AMA but also showed more excessive defects in CVS from spontaneous abortion (SA), including four AMA-related DMRs whose nearby genes overlapped with AMA-related differentially expressed genes (DEGs) (CDK11A, C19orf71, COL5A1, and GNE). The decreased DNA methylation level of DMR near GNE was positively correlated with the downregulated expression of GNE in AMA. Single-cell atlas further revealed comparatively high expression of GNE in the trophoblast lineage, and knockdown of GNE in HTR8-S/Vneo cells significantly impaired cellular proliferation and migration.

Conclusion
Our study provides valuable resources for investigating AMA-induced epigenetic abnormalities and provides new insights for explaining the increased risks of pregnancy complications in AMA pregnancies.

Graphical Abstract
Temporal changes in plankton diversity in relation to hydrographical characteristics at Perumal Lake, Cuddalore District, Tamil Nadu, India
Authors: Aravinth Annamalai , Kannan Radhakrishnan , Chinnadurai Gunasekaran , Manickam Narasimman , Raju Piliyan , Perumal Pachiappan , Santhanam Perumal 
Published: March 2023

Abstract
Background
The fresh water environment supports the productivity of phyto- and zooplankters and fin and shell fishes. The rate of fish productivity of an aquatic ecosystem solely depends on the rate of plankton productivity, and which in turn critically depend on the concentration and variation of hydrographical features. The current investigation was focused on the distributional pattern of phyto- and zooplankton vis-à-vis physicochemical characteristics in Perumal Lake, Cuddalore District, Tamil Nadu State (India).

Results
The hydrographical factors and phytoplankton as well as zooplankton diversity were studied at the monthly interval of 12 months by following the standard methods in freshwater of Perumal Lake from September 2018 to August 2019. Presently a total of 15 species of phytoplankton and 15 species of zooplankton were recorded in Perumal Lake. The present study reveals good variation in the hydrographical characteristics, such as temperature (24.2–30.1 °C), turbidity (10.4–43.2 NTU), total suspended solids (300.2–1800.8 mg/L), conductivity (3.25–10.54 mhos/cm), pH (6.92–8.2), total hardness (8.58–23.8 mg/L), dissolved oxygen (2.8–7.26 mg/L), dissolved carbon dioxide (0.96–13.2 mg/L), chloride (1.92–23.8 mg/L), nitrate (0.28–3.18 mg/L), sulphate (1.1–8.2 mg/L) and phosphate (0.19–3.34 mg/L).

Conclusions
The findings of the present study indicate that the temperature has influence on phytoplankton as well as zooplankton diversity of species. Regular monitoring of hydro-biological parameters is necessary to assess the health of the lake ecosystem.
Mother and father depression symptoms and child emotional difficulties: a network model
Authors: Martin Alex F. , Maughan Barbara , Konac Deniz , Barker Edward D. 
Published: March 2023

BackgroundMother and father depression symptoms often co-occur, and together can have a substantial impact on child emotional well-being. Little is understood about symptom-level mechanisms underlying the co-occurrence of depression symptoms within families.AimsThe objective was to use network analysis to examine depression symptoms in mothers and fathers after having a baby, and emotional symptoms in children in early adolescence.MethodWe examined data from 4492 mother–father–child trios taken from a prospective, population-based cohort in the UK. Symptoms were examined using two unregularised partial correlation network models. The initial model was used to examine the pattern of associations, i.e. the overall network structure, for mother and father depression symptoms, and then to identify bridge symptoms that reinforce depression symptoms between parents during offspring infancy. The second model examined associations between the parent symptom network, including bridge symptoms, with later child emotional difficulties.ResultsThe study included 4492 mother–father–child trios; 2204 (49.1%) children were female. Bridge symptoms reinforcing mother and father depression symptoms were feeling guilty and self-harm ideation. For mothers, the bridge symptom of feeling guilty, and symptoms of anhedonia, panic and sadness were highly connected with child emotional difficulties. For fathers, the symptom of feeling overwhelmed associated with child emotional difficulties. Guilt and anhedonia in fathers appeared to indirectly associate with child emotional difficulties through the same symptom in mothers.ConclusionsOur findings suggest that specific symptom cascades are central for co-occurring depression in parents and increased vulnerability in children, providing potential therapeutic targets.
Implementation of Systematic Financial Screening in an Outpatient Breast Oncology Setting
Authors: Beauchemin Melissa P. , DeStephano David , Raghunathan Rohit , Harden Erik , Accordino Melissa , Hillyer Grace C. , Kahn Justine M. , May Benjamin L. , Mei Billy , Rosenblat Todd , Law Cynthia , Elkin Elena B. , Kukafka Rita , Wright Jason D. , Hershman Dawn L. 
Published: March 2023

PURPOSEImplementation of routine financial screening is a critical step toward mitigating financial toxicity. We evaluated the feasibility, sustainability, and acceptability of systematic financial screening in the outpatient breast oncology clinic at a large, urban cancer center.METHODSWe developed and implemented a stakeholder-informed process to systematically screen for financial hardship and worry. A 2-item assessment in English or Spanish was administered to patients through the electronic medical record portal or using paper forms. We evaluated completion rates and mode of completion. Through feedback from patients, clinicians, and staff, we identified strategies to improve completion rates and acceptability.RESULTSFrom March, 2021, to February, 2022, 3,500 patients were seen in the breast oncology clinic. Of them, 39% (n = 1,349) responded to the screening items, either by paper or portal, 12% (n = 437) preferred not to answer, and the remaining 49% (n = 1,714) did not have data in their electronic health record, meaning they were not offered screening or did not complete the paper forms. Young adults (18-39 years) were more likely to respond compared with patients 70 years or older (61% v 30%, P < .01). English-preferring patients were more likely to complete the screening compared with those who preferred Spanish (46% v 28%, P < .01). Non-Hispanic White patients were more likely to respond compared with Non-Hispanic Black patients and with Hispanic patients (46% v 39% v 32%, P < .01). Strategies to improve completion rates included partnering with staff to facilitate paper form administration, optimizing patient engagement with the portal, and clearly communicating the purpose of the screening.CONCLUSIONSystematic financial screening is feasible, and electronic data capture facilitates successful implementation. However, inclusive procedures that address language and technology preferences are needed to optimize screening.
Open questions in marine mammal sensory research
Authors: De Vreese Steffen , Sørensen Kenneth , Biolsi Kristy , Fasick Jeffry I. , Reidenberg Joy S. , Hanke Frederike D. 
Published: March 2023

ABSTRACTAlthough much research has focused on marine mammal sensory systems over the last several decades, we still lack basic knowledge for many of the species within this diverse group of animals. Our conference workshop allowed all participants to present recent developments in the field and culminated in discussions on current knowledge gaps. This report summarizes open questions regarding marine mammal sensory ecology and will hopefully serve as a platform for future research.
Ratiometric sensing of Pnt and Yan transcription factor levels confers ultrasensitivity to photoreceptor fate transitions in Drosophila
Authors: Bernasek Sebastian M. , Hur Suzy S. J. , Peláez-Restrepo Nicolás , Boisclair Lachance Jean-François , Bakker Rachael , Navarro Heliodoro Tejedor , Sanchez-Luege Nicelio , Amaral Luís A. N. , Bagheri Neda , Rebay Ilaria , Carthew Richard W. 
Published: March 2023

ABSTRACT
Cell state transitions are often triggered by large changes in the concentrations of transcription factors and therefore large differences in their stoichiometric ratios. Whether cells can elicit transitions using modest changes in the ratios of co-expressed factors is unclear. Here, we investigate how cells in the Drosophila eye resolve state transitions by quantifying the expression dynamics of the ETS transcription factors Pnt and Yan. Eye progenitor cells maintain a relatively constant ratio of Pnt/Yan protein, despite expressing both proteins with pulsatile dynamics. A rapid and sustained twofold increase in the Pnt/Yan ratio accompanies transitions to photoreceptor fates. Genetic perturbations that modestly disrupt the Pnt/Yan ratio produce fate transition defects consistent with the hypothesis that transitions are normally driven by a twofold shift in the ratio. A biophysical model based on cooperative Yan-DNA binding coupled with non-cooperative Pnt-DNA binding illustrates how twofold ratio changes could generate ultrasensitive changes in target gene transcription to drive fate transitions. Thus, coupling cell state transitions to the Pnt/Yan ratio sensitizes the system to modest fold-changes, conferring robustness and ultrasensitivity to the developmental program.
SLC25A46 promotes mitochondrial fission and mediates resistance to lipotoxic stress in INS-1E insulin-secreting cells
Authors: Santo-Domingo Jaime , Lassueur Steve , Galindo Antonio Núñez , Alvarez-Illera Pilar , Romero-Sanz Silvia , Caldero-Escudero Elena , de la Fuente Sergio , Dayon Loïc , Wiederkehr Andreas 
Published: March 2023

ABSTRACT
Glucose sensing in pancreatic β-cells depends on oxidative phosphorylation and mitochondria-derived signals that promote insulin secretion. Using mass spectrometry-based phosphoproteomics to search for downstream effectors of glucose-dependent signal transduction in INS-1E insulinoma cells, we identified the outer mitochondrial membrane protein SLC25A46. Under resting glucose concentrations, SLC25A46 was phosphorylated on a pair of threonine residues (T44/T45) and was dephosphorylated in response to glucose-induced Ca2+ signals. Overexpression of SLC25A46 in INS-1E cells caused complete mitochondrial fragmentation, resulting in a mild mitochondrial defect associated with lowered glucose-induced insulin secretion. In contrast, inactivation of the Slc25a46 gene resulted in dramatic mitochondrial hyperfusion, without affecting respiratory activity or insulin secretion. Consequently, SLC25A46 is not essential for metabolism–secretion coupling under normal nutrient conditions. Importantly, insulin-secreting cells lacking SLC25A46 had an exacerbated sensitivity to lipotoxic conditions, undergoing massive apoptosis when exposed to palmitate. Therefore, in addition to its role in mitochondrial dynamics, SLC25A46 plays a role in preventing mitochondria-induced apoptosis in INS-E cells exposed to nutrient stress. By protecting mitochondria, SLC25A46 might help to maintain β-cell mass essential for blood glucose control.
Digital Twins along the product lifecycle: A systematic literature review of applications in manufacturing
Authors: Pronost Guillaume , Mayer Frédérique , Camargo Mauricio , Dupont Laurent 
Published: March 2023

Background: The evolution of product expectations in the era of mass customization implies an improvement and a better control of individualized creation and production processes throughout the product lifecycle. The application of the digital twin (DT) seems to be a favoured solution in this context, but its study during the lifecycle of a product has only been partially evoked in the literature. Methods: The purpose of this state-of-the-art article is to identify current trends of applications of the digital twin concept in the literature under two main dimensions: its nature regarding the interaction structure between digital and physical objects (defined as: Pre-Digital Twin, digital model, digital shadow, and digital twin), but also its applications, along the product lifecycle (Design, Production, Operation, Disposal). To achieve this analysis a systematic literature review was carried out. The publications selection was based on the presence in this of a case of application of a digital twin with a focus in the Manufacturing sector. Within this review, 188 scientific papers were compiled and analyzed. Results: Results showed that although the term digital twin is widely used, the deployment of DT technologies in manufacturing is still at an early stage as most of the digital twin applications were in fact prototypes focused on the real-time observability of the physical system, either for optimization or predictive maintenance. Moreover, regarding the product lifecycle, most of the applications have been focused on the production and operational phases whereas those at the design and disposal phases are still limited. Conclusions: This paper presents an original approach to the study of digital twins, not focusing on a single application area or lifecycle phase but which aims to establish future perspectives on the use of digital twins along the lifecycle.
A cross-sectional survey among parents to report challenges and barriers in the administration of medicines to children in United Arab Emirates
Authors: AlKaddour Nour Aliyan , Shah Rawa Banoori , Gillani Syed Wasif , Sharafi Niloofar Hadi , Khan Aiman Fatima , Elshafie Riham Mohamed , Rathore Hassaan Anwer 
Published: March 2023

Background: Lack of knowledge among parents can result in inappropriate administration practices. After analyzing different studies among children, there was no data on challenges and barriers in the administration of medicines among children in this region because of the diverse environmental issues and challenges in the UAE. The objective of this study was to determine the reported administration practices of parents and challenges and barriers in the administration of medicines among children in UAE. Methods: A questionnaire-based survey was conducted. A convenience sampling technique was used to collect the data. An online Raosoft® sample size calculator was applied (n = 248). The inclusion criteria were parents who had a child under 10 years of age and gave consent to participate in this study. Children with vision problems, cognitive/physical disabilities, and caregivers other than parents were excluded from this study. Results: The study reported response rate of 73.2%. The mean ± S.D age of the parents in years was 35.5 ± 7.8, and the mean ± S.D of children aged years was 2.60 ± 1.54. 26.2% of parents reported treatment failure due to oral medicine administration. A total of 22.2% of parents reported that they gave medicines in doses higher than prescribed by the doctor to treat their children more quickly. Similarly, a total of 64.5% of the parents reported self-medication without consultation from a healthcare provider. Conclusions: The study concluded that there were inappropriate medicine administration practices among parents. Parents reported administration of higher doses to treat their children quickly.
Virtual screening for chemical analogues similar to phytochemicals that inhibit aldose reductase in the development of diabetic microvascular complications
Authors: Otieno Filex , Kagia Richard 
Published: March 2023

Background: The polyol pathway contributes to the development of diabetic complications but can be inhibited by plant phytochemicals. This study aimed at assessing analogs of specific flavonoids that delay onset of microvascular complications with better pharmacokinetic and toxicology profiles. Methods: An in silico study design was employed. The phytochemicals luteolin and quercetin were selected. Analogs were obtained from ZINC database and prepared using Avogadro software. Docking analysis was done using AutoDock Vina embedded in Chimera. Ligand enzyme interaction was carried out using Biovia Discovery studio. Pharmacokinetic and toxicological profiling was carried out using SWISSADME and protox server. A total of 40 analogues were analyzed. Sulindac was used as the comparator besides original phytochemicals. Results: Docking analysis showed both luteolin and quercetin (-9.7) had a slightly stronger affinity for inhibiting aldose reductase compared with sulindac (-9.6). Eight analogues of luteolin and 14 analogues of quercetin showed stronger affinity with the highest registered at -10.6. Both luteolin and quercetin did not violate the Lipinski rule, had high GI absorption, did not cross the blood brain barrier nor were p-glycoprotein substrates, and inhibited CYP1A2, CYP2D6 and CYP3A4. The LD50 of luteolin (3,919 mg/kg) was high indicating excellent safety profile. Quercetin had a low LD50 (159 mg/kg). All 22 analogues exhibited similar pharmacokinetic profiles to their respective phytochemical. However, they did differ in terms of docking strength and toxicology analysis. Six out of the eight luteolin analogues had LD50=3,919 mg/kg, while the remaining had LD50=159 mg/kg. Five quercetin analogues had LD50 of 159 mg/kg, another five had LD50=3,919 mg/kg and the rest had LD50=4,000 mg/kg, while the other two had a LD50 of 5,000 mg/kg. Conclusions: In conclusion, six ZINC compounds similar to luteolin and nine similar to quercetin had stronger binding affinity for aldose reductase and superior toxicological profile compared to parent phytochemicals.
Promising effect of cisplatin and melatonin combination on the inhibition of cisplatin resistance in ovarian cancer
Authors: Adeya Adella Cut , Siregar M Fidel Ganis , Putra Imam B , Hasibuan Poppy Anjelisa , Andrijono Andrijono , Bachtiar Adang , Lumbanraja Sarma N , Nasution Iqbal P 
Published: March 2023

Background: Ovarian cancer management has not yet given a satisfactory result, and the recurrence rate is still high. One of the reasons for this is resistance to chemotherapy. Melatonin and cisplatin may be involved in the chemotherapy resistance of ovarian cancer. Methods: A laboratory experiment was performed using melatonin and cisplatin in the SKOV3 cell, from September 2020 to November 2021 at the SCTE and Integrated Laboratory & Research Center Universitas Indonesia. Several variables were used, such as doxorubicin, melatonin, cisplatin, and combination of cisplatin and melatonin at several concentrations (1×, 3/4×, 1/2×, and 1/4×). A total of 24 samples were included and divided into 8 groups. The IC50 values of melatonin, doxorubicin, and cisplatin as well as cell viability was calculated via MTS assay. Subsequently, flow cytometry was performed to assess the effect of cisplatin and melatonin on the mechanisms of CTR1, p-glycoprotein, GSH, ERCC1, e-cadherin, and apoptosis. Analysis of variance and Bonferroni test were employed for the study. Results: The IC50 values of melatonin, cisplatin, and doxorubicin were 1.841 mM, 117.5 mM, and 14.72 mM, respectively. The combination groups of cisplatin and melatonin reduced cell viability; decreased the CTR1 mean (19.73), Pgp (6.7), GSH (11.73), and ERCC1 (4.27) in the combination 1 (C1) group; and increased e-cadherin (32.2) and annexin V (53.57) also in the combination 1 (C1) group. Conclusions: The combination of melatonin and cisplatin might have an impact on drug resistance via several mechanisms in ovarian cancer.
Enhancing workplace exercise and physical fitness: university workers’ attitudes
Authors: Boonsem Aungkana , Malarat Anan , Na Phatthalung Aditep 
Published: March 2023

Background: Workplace exercise (WE) has become the focus of a number of studies in Thailand universities as it is believed to prevent numerous chronic diseases. This study aims to illustrate and investigate the behavioral factors related to the physical fitness of university workers and attitudes in work performance. Methods: We conducted a quasi-experimental study on 93 workers with purposive sampling using the Taro Yamane method, to examine exercise behaviors and knowledge, attitude, and exercise practice. Then, 31 selected participants who were at a moderate level of attitude and exercise practice joined the workplace exercise program for two months. Participants’ exercise behavior and knowledge, attitude, and exercise practice before and after joining the program were analyzed using an independent t-test. The physical fitness and work attitude were examined. Results: The results show that the university workers who participated in the program had an adjustment in exercise behavior after engaging in WE with a high level of knowledge, attitude (3.14+.18) and exercise practice (3.32+.31). In addition, we found that programs improved physical fitness with a significant increase in resting heart rate and leg strength (p<0.05). A direct relationship between work attitude and physical fitness after adapting intervention were revealed with work attitude in 3.35+.44 high agreement. Conclusion: The results correspond to earlier studies on exercise factors with the increasing exercise behavior level in terms of knowledge, attitude, and exercise practice. The WE is important for university workers. Therefore, the developed WE in the workplace increased the health and work attitude.
State-of-the-art of miliary tuberculosis in children: protocol for a scoping review of the literature
Authors: Buonsenso Danilo , Mariani Francesco , Morello Rosa , Song Rinn 
Published: March 2023

Background: Miliary Tuberculosis (TB) is a rare manifestation of TB described in both adults and children. Pediatirc reports are rare and therefore evidence about diagnostics and management is scarce. Methods: We will start our research in March 2023 in the following bibliographic databases: PubMed, EMBASE, Cochrane and SCOPUS. The main review question will be “What are the main clinical characteristics and outcomes of pediatric miliary TB reported in the literature?” We will include randomized and non-randomized controlled trials, prospective and retrospective observational studies, performed on children and adolescents (younger than 18 years), hospitalized or not, with a confirmed diagnosis of miliary TB. To report our findings, we will follow Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. Dissemination: The findings of this review will be published in international peer-reviewed journals and presented in pediatric infectious diseases national and international conferences.