bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility and Acceptability of the Mazi Umntanakho Digital Tool in South African Settings: A Qualitative Evaluation
Authors: Draper Catherine E. , Cook Caylee J. , Ankrah Elizabeth A. , Beltran Jesus A. , Cibrian Franceli L. , Lakes Kimberley D. , Mofid Hanna , Williams Lucretia , Hayes Gillian R.
Published: January 2025

To address the need for interventions targeting social emotional development and mental health of young children in South Africa, the Mazi Umntanakho (‘know your child’) digital tool was co‐designed, and piloted with caregivers and 3–5‐year‐old children involved in home visiting programmes promoting early childhood development. The aim of this study was to qualitatively evaluate the feasibility and acceptability of this tool in four urban and four rural low‐income communities, from the perspective of home visitors and caregivers. Focus groups were conducted with home visitors (n = 117) and caregivers (n = 72). Issues relating to the feasibility of implementing the tool included timing of using the tool, technical and social implementation challenges, WhatsApp as the preferred platform, and participants' recommendations for future implementation. Overall, the tool was acceptable for home visitors and caregivers and was perceived to have a positive impact on children's development, and the relationship between caregivers and children.
Comparison of ovarian reserve after laparoscopic cystectomy in patients with ovarian endometriosis differ in cyst size: A systematic review and meta‐analysis
Authors: Liu Weihe , Zhao Tingting , Zheng Zetong , Huang Jia , Tan Jifan
Published: January 2025

Background

Whether cyst size affects ovarian reserve before and after surgery remains controversial.

Objective

The objective of this study is to determine whether cyst size causes differences in pre‐ and post‐ovarian reserve impairment among patients with endometrioma.

Search Strategy

PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure were searched from inception to October 13, 2023.

Selection Criteria

We included prospective studies comparing the ovarian reserve parameters of patients with endometrioma preoperatively and at different time points postoperatively between large and small groups, determined by self‐defined cut‐off values in eligible studies.

Data Collection and Analysis

Bias was assessed using the Newcastle–Ottawa Scale. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were used for outcome measures.

Main Outcome Measure(s)

The main outcome measures are serum anti‐Müllerian hormone (AMH) and antral follicle count (AFC) preoperatively and at different time points postoperatively (primary and secondary aims).

Main Results

Seven trials (603 participants) were included, all of which qualified for meta‐analysis. Irrespective of the cut‐off values, the SMD showed that the serum AMH level was significantly lower in large groups at 1 month postoperatively (SMD = −0.515 ng/mL, 95% CI [−0.858, −0.172], P = 0.003, = 44.3%). Subgroup analyses indicated that when the cut‐off values were limited to 5 cm in diameter, the AMH levels were significantly lower in large groups (SMD = −0.822 ng/mL, 95% CI [−1.605, −0.039], P = 0.040, = 58.3%) 1 month after the surgery, and when cut‐off values were limited to 7 cm, even at 3 months postoperatively, the serum AMH levels of patients with large endometrioma were still significantly lower than those with small endometrioma (SMD = −0.531 ng/mL, 95% CI [−0.818, −0.245], P = 0.000, = 0.0%). However, when cut‐off values were not limited, the serum AMH levels did not differ significantly (P > 0.05) between the groups preoperatively and at 3, 6, and 12 months postoperatively. Additionally, there were no significant differences (P > 0.05) in the AFC between the groups preoperatively and 1 month postoperatively.

Conclusion

AMH in patients with different endometrioma sizes recovered to the same level at 6 months postoperatively. Our study provides guidance for the clinical prognostic assessment of patients with large endometriomas after laparoscopic cystectomy.

Systematic review registration: CRD42023481967(PROSPERO).
Sustainable Intensification of Forage Cactus by Intercropping Increases Productivity, Profitability and Water Use Efficiency
Authors: Salvador Kaique Renan da Silva , Jardim Alexandre Maniçoba da Rosa Ferraz , Alves Cleber Pereira , Morais José Edson Florentino de , Araújo Júnior George do Nascimento , Souza Carlos André Alves de , Silva Marcelo José da , Santos João Pedro Alves de Souza , Silva Gabriel Italo Novaes da , Santos Agda Raiany Mota dos , Souza Luciana Sandra Bastos de , Queiroz Mário Adriano Ávila , Tabosa José Nildo , Silva Thieres George Freire da
Published: January 2025

The objective of this study was to evaluate the changes in growth, productive performance, soil water dynamics, efficiency and economic return in production systems with forage cactus under monoculture and intercropping. The two experiments were conducted during 2017 and 2020 in the semi‐arid region of Brazil. The forage cactus experiment involved monoculture and intercropping with pigeon pea, forage sunflower and sorghum (‘2502’) in all systems with mulch in the soil. The second forage cactus experiment involved monoculture and intercropping with millet and sorghum varieties (‘SF15’ and ‘1011’) without mulch in the soil. The cutting time was reduced by 155 accumulated degree‐days (51 days) in the cactus‐‘1011’ system. The cactus‐‘2502’ and cactus‐‘SF15’ systems presented the highest yields, with fresh and dry matter values equal to 272 and 52 Mg ha−1 (~13 months) and 1025 and 93 Mg ha−1 (~16 months), respectively. In general, the actual evapotranspiration of the intercropped crops was relatively high in terms of revenue, with the cactus‐‘SF15’ crop standing out (US$ 26,100). Although intercropping affects the individual growth of the forage cactus, it promotes greater productivity (cactus‐‘2502’ and cactus‐‘SF15’), earlier cutting (cactus‐‘1011’), water use efficiency (cactus‐‘2502’ and cactus‐‘SF15’) and economic return for the production system (cactus‐‘2502’ and cactus‐‘SF15’).
Hypoxia‐Inducible Factor‐1α Regulates BNIP3‐Dependent Mitophagy and Mediates Metabolic Reprogramming Through Histone Lysine Lactylation Modification to Affect Glioma Proliferation and Invasion
Authors: Dong Feng , Yin Haichang , Zheng Zhixing
Published: January 2025

Objective

Gliomas are the predominant form of malignant brain tumors. We investigated the mechanism of hypoxia‐inducible factor‐1α (HIF‐1α) affecting glioma metabolic reprogramming, proliferation and invasion.

Methods

Human glioma cell U87 was cultured under hypoxia and treated with small interfering (si)HIF‐1α, si‐B cell lymphoma‐2/adenovirus E1B 19‐kDa interacting protein 3 (siBNIP3), si‐YT521‐B homology domain 2 (siYTHDF2), 3‐methyladenine and 2‐deoxyglucose, with exogenous sodium lactate‐treated normally‐cultured cells as a lactate‐positive control. Cellular hexokinase 2, lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 enzyme activities, glucose uptake, and levels of lactic acid and adenosine triphosphate (ATP), and HIF‐1α, glycolysis‐related proteins, mitophagy‐related proteins, histone H3 lysine 18 lactylation (H3K18la) and YTHDF2 were determined by ELISA, 2‐NBDG, kits, and Western blot. Extracellular acidification rate (ECAR), and cell proliferation, invasion, apoptosis and mitophagy were evaluated by extracellular flux analysis, CCK‐8, Transwell, flow cytometry, and immunofluorescence staining. H3K18la‐YTHDF2 relationship and YTHDF2‐BNIP3 interaction were assessed by ChIP and Co‐IP assays.

Results

Hypoxia‐induced highly‐expressed HIF‐1α in glioma cells increased glycolysis‐related protein levels, glycolytic enzyme activities, glucose uptake, lactic acid production, ATP level and ECAR, thereby promoting metabolic reprogramming, invasion and proliferation. HIF‐1α mediated metabolic reprogramming, proliferation and invasion through BNIP3‐dependent mitophagy, which were partly negated by mitophagy inhibition. HIF‐1α induced histone Kla modification to upregulate YTHDF2. YTHDF2 downregulation impeded YTHDF2‐BNIP3 interaction and inhibited HIF‐1α‐induced BNIP3‐dependent mitophagy, curbing glioma cell metabolic reprogramming, proliferation and invasion.

Conclusions

Hypoxia‐induced high HIF‐1α expression upregulated YTHDF2 through hH3K18la modification, enhanced YTHDF2‐BNIP3 interaction, and regulated BNIP3‐dependent mitophagy‐mediated metabolic reprogramming to affect glioma proliferation and invasion.
B4GALNT1 Regulates Hepatocellular Carcinoma Cell Proliferation and Apoptosis via the PI3K–AKT–mTOR Pathway
Authors: Bie Lihan , Chen Guangquan , Lei Xin , Xiao Feng , Xu Zheng , Xiang Zhouhong , Lu Zhicheng , Jiang Xiudi
Published: January 2025

Background

Hepatocellular carcinoma (HCC) is a ubiquitous malignancy linked to significant mortality. The abnormal expression of β‐1,4‐N‐acetyl‐galactosaminyltransferase 1 (B4GALNT1) seemed to be implicated in tumorigenesis. Nonetheless, this enzyme's roles in HCC are unclear.

Methods

By analyzing the TCGA_LIHC, GSE77509, and GSE135631 datasets, the levels of B4GALNT1 expression in HCC and surrounding non‐cancerous tissues were compared. The prognostic implications of B4GALNT1 were assessed using the Cox regression analysis (CRA). The relationship of B4GALNT1 mutations with CpG island methylation levels and prognosis was examined by analyzing the cBioPortal and MethSurv databases. We sifted the evidence of B4GALNT1 expression correlating with 28 immune cell types' infiltration by harnessing the “GSVA” R package. To delve into the influences of genes associated with B4GALNT1 on HCC, we implemented gene set enrichment analysis (GSEA). We constructed a lentiviral vector expressing B4GALNT1 and knocked down B4GALNT1 in HepG2 cells. The resulting effects on HCC cell proliferation and apoptosis were analyzed via cell proliferation assays and flow cytometry.

Results

HCC tissues presented significant B4GALNT1 overexpression relative to surrounding non‐cancerous tissues, marking it as a standalone risk factor for HCC progression. Methylation levels of two CpG islands were high, suggesting poor prognosis. It was detectable that B4GALNT1 expression interrelated with the infiltration extent of natural killer T cells in HCC tissues. B4GALNT1‐fueled cell proliferation and enhanced resistance to apoptosis in HCC cells.

Conclusion

B4GALNT1 is a strong regulator of HCC progression and holds promise as a marker for prognosis and a hallmark for therapy in HCC.
Prevalence of Cachexia and Outcomes in Patients With Chronic Diseases: A National Database Analysis of 5 484 103 Hospitalisations
Authors: Lainscak Mitja , Zupanic Tina , Omersa Daniel , Erzen Ivan , Farkas Jerneja
Published: January 2025

Background

Cachexia is a frequent companion of chronic diseases and a well‐established predictor of poor patient performance and outcome. Since cachexia as a discharge diagnosis is not much investigated, we aimed to investigate prevalence of cachexia in hospitalised patients and their outcome.

Methods

We conducted a retrospective analysis of the National Hospital Health Care Statistics Database using the 10th revision of the International Classification of Diseases codes. During period 2004–2019, patients with cachexia were identified, as well as patients with cancer, heart failure, chronic obstructive pulmonary disease and chronic kidney disease. The primary endpoint was the discharge code of cachexia; secondary endpoints were length of hospital stay, in‐hospital and post discharge all‐cause mortality.

Results

In period 2004–2019, 5 484 103 hospitalisations were screened; cachexia was coded 19 348 times (0.35%) in 14 089 patients (67 ± 13 years, 42% women). From 2004 to 2019, prevalence of cachexia increased steadily from 1.2% to 1.9%, which was most prominent for cancer and chronic obstructive pulmonary disease. At one year post discharge, 49% patients with cachexia were dead as compared to 26% in patients without cachexia. In Cox multivariate analysis, cachexia predicted post‐discharge death in any of chronic diseases (hazard ratio of 1.28 in heart failure to 1.47 in chronic kidney disease).

Conclusions

In our report from a National Hospital Health Care Statistics Database, we found that cachexia was underreported as ICD‐10 coded discharge diagnosis in patients with chronic diseases. When diagnosed, it was associated with higher hazard of post discharge mortality.
The extinction burst: Effects of reinforcement magnitude
Authors: Shahan Timothy A. , Avellaneda Matias
Published: January 2025

The extinction burst is an increase in an operant behavior early in the transition to extinction. A matching‐law‐based quantitative theory suggests that it results from the elimination of competition from reinforcement‐related behavior that accompanies the transition to extinction. This experiment examined the effects of reinforcement magnitude on the extinction burst with rats. Responding produced either 1 pellet or 6 pellets prior to a within‐session transition to extinction. Baseline response rates were lower with 6 pellets than with 1 pellet but increased more in the first minute of extinction following 6 pellets. Furthermore, an order effect was observed where rats having first experienced extinction following 1 pellet showed a smaller extinction burst when subsequently trained with 6 pellets—an outcome resulting from a faster deceleration of responding during extinction. The model described the data well, including the order effect, when augmented to include the potential asymmetrical influence of learning to discriminate the continued absence of different magnitudes of reinforcement. We conclude that the approach holds promise by formally incorporating the extinction burst into the corpus of matching theory and serving as an example of the utility of better aligning basic research methods and theorizing with areas of applied concern.
A Single‐Center Retrospective Cohort Study of Biopterin Metabolism Disorders in the United Arab Emirates
Authors: Jarrah Omar , Nouri Mahmood , Al Shamsi Aisha
Published: January 2025

Background

Tetrahydrobiopterin (BH4) deficiencies comprise a group of five neurometabolic disorders caused by five genetic defects responsible for BH4 biosynthesis and regeneration. Their global prevalence remains unknown, and variance exists among different countries.

Aims

To describe clinical, biochemical, molecular genetic data and follow‐up of patients with BH4 deficiency seen in Tawam Hospital.

Methods

A retrospective study of all patients with BH4 disorders who were followed up between January 2010 and December 2023 in Tawam Hospital. All data were retrieved from patients' electronic charts, including baseline characteristics, developmental milestones, family history, and clinical examination. Radiological and laboratory investigations, including phenylalanine levels, prolactin levels, CSF study, urine and plasma pterin profiles, and molecular tests, were reviewed.

Results

Ten patients with BH4 deficiencies were found. The youngest patient was diagnosed at 3‐ weeks, and the oldest was nine; 70% were male, consanguineous 80%, and 40% were Emirati. Prematurity was reported in two patients. Intrauterine growth restriction was found in 70%, and microcephaly in 40%. Eighty percent had developmental delay, and 2 patients had behavioral issues. Seizure and movement disorders were reported in five and three patients, respectively. Brain MRI showed cortical atrophic changes, corpus callosum hypoplasia, hyperintensities in the parieto‐occipital region, and periventricular white matter. Abnormal Newborn screening was found in 60%, with initial high phenylalanine levels (>120 μmol/L) in 80%. Prolactin level was high in all studied patients. Four patients' cerebrospinal fluid neurotransmitter metabolites were evaluated. Blood for DHPR screening and urine pterin profile were done on eight patients. Nine patients had molecular testing. DHPR deficiency was most commonly reported among studied patients (50%), with five novel variants in the QDPR gene. The second prevalent disorder was PTPS deficiency and only one patient with SR deficiency.

Conclusion

This cohort offers an in‐depth clinical and genetic understanding of BH4 deficiencies from a single center in the UAE. It describes new genetic variants and addresses diagnostic challenges to enhance the patient's diagnosis and treatment.
Ecomorphology of South American Penguins
Authors: Bloom Elliott , Torres‐Mura Juan Carlos , Bertellotti Marcelo , Hertel Fritz
Published: January 2025

A major goal of evolutionary ecology is to understand the interaction between ecological differences and the functional morphology of organisms. Studies of this type are common among flying birds but less so in penguins. Penguins (Spheniscidae) are the most derived extant underwater flying birds using their wings for swimming and beak when foraging. The Humboldt Penguin (Spheniscus humboldti) and Magellanic Penguin (S. magellanicus) occur along the coast of South America and their morphology was compared in allopatry and sympatry throughout their ranges. Measurements included: mass, tarsus length, four beak/head dimensions, bite force, wing loading, and aspect ratio. A thin‐plate spline/relative warp analysis was also used to detect subtle differences in wing shape. Both species generally overlapped in trait morphology, but Magellanic Penguins showed greater trait diversity. Wing morphology was more homogenous between species than beak morphology indicating a similar mode of locomotion but potential differences in prey procurement. Morphological character displacement in sympatry was only evident in beak length. Local adaptation was common in other traits, and Punta Norte (Argentina) was often distinct in having high variation, notably in beak depth, wing loading, and wing shape (relative warp 1). This may be attributed to the fact that penguins here dive deep and forage farther from their colony; they also have a greater colony size that may contribute to greater intraspecific competition for resources. These results support a potentially optimal wing design for aquatic movement, which likely applies to other penguin species. Differences in morphology may also be related to differences between Atlantic and Pacific ecosystems.
Human Cytomegalovirus Infection Induces Long‐Term Changes in the Cytokine Milieu of Kidney Transplant Recipients
Authors: Redondo Natalia , Valverde‐Manso Andrea , Ruiz‐Merlo Tamara , Rodríguez‐Goncer Isabel , Parra Patricia , López‐Medrano Francisco , González Esther , Polanco Natalia , San Juan Rafael , Andrés Amado , Aguado José María , Fernández‐Ruiz Mario
Published: January 2025

The impact of human cytomegalovirus (HCMV) infection on the mid‐ and long‐term balance between pro‐inflammatory and anti‐inflammatory cytokines among kidney transplant recipients (KTRs) remains unclear. We measured plasma levels of 12 Th1/Th2‐type cytokines (granulocyte‐macrophage colony‐stimulating factor, interferon‐γ, interleukin [IL]‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐18 and tumor necrosis factor‐α) in a cohort of 290 KTRs at four time points through month 12 after transplantation. Cytokine levels at each point were compared according to the previous documentation of HCMV replication by two approaches: “cumulative exposure” from the time of transplantation and “recent exposure” within the 2–3 months preceding cytokine assessment. Significance levels were Bonferroni‐corrected for multiple pairwise comparisons. Plasma levels of IL‐6, IL‐10, and IL‐12p70 at month 1 were significantly increased in KTRs that had experienced HCMV infection during the first 30 days. By month 3, IL‐6 and IL‐10 remained increased in KTRs with cumulative exposure through day 90. Cumulative exposure to HCMV replication through day 180 was also associated to increased IL‐10 levels at month 6. In addition, KTRs with recent HCMV exposure had increased IL‐10 levels at months 3 and 6. After multivariable adjustment, cumulative exposure to HCMV infection and/or the area under curve of HCMV DNAemia during the corresponding period were associated to IL‐10 levels within the highest quartile at months 1, 3, and 6. Preceding HCMV infection induces sustained changes in the plasma cytokine milieu of KTRs, with elevated IL‐6 and IL‐10 levels throughout the first 6 months after transplantation.
Modulation of Lymphotoxin β Surface Expression by Kaposi's Sarcoma‐Associated Herpesvirus K3 Through Glycosylation Interference
Authors: Kang Soowon , Brulois Kevin , Choi Youn Jung , Zhang Shaoyan , Jung Jae U.
Published: January 2025

Kaposi's sarcoma‐associated herpesvirus (KSHV) employs diverse mechanisms to subvert host immune responses, contributing to its infection and pathogenicity. As an immune evasion strategy, KSHV encodes the Membrane‐Associated RING‐CH (MARCH)‐family E3 ligases, K3, and K5, which target and remove several immune regulators from the cell surface. In this study, we investigate the impact of K3 and K5 on lymphotoxin receptor (LTβR) ligands, LTβ and LIGHT, which are type II transmembrane proteins and function as pivotal immune mediators during virus infection. Upon co‐expression of viral MARCH proteins with LTβR ligands, we showed that K3 and K5 selectively targeted LTβ, but not LIGHT, for the downregulation of surface expression. Specifically, K3 and K5 E3 ligases interacted with the transmembrane domain of LTβ. Intriguingly, K3 interacted with an immature form of LTβ, whereas K5 targeted the fully mature form. Subsequent biochemical analyses revealed that K3 disrupted the initial steps of N‐glycosylation maturation of LTβ. This interference resulted in the sequestration of LTβ within the endoplasmic reticulum, impeding its trafficking to the plasma membrane. Consequently, the K3‐mediated downregulation of LTβ surface expression suppressed the LTβR downstream signaling pathway. These findings uncover a novel mechanism by which KSHV K3 E3 ligase inhibits the membrane trafficking pathway of the LTβ inflammatory ligand through glycosylation interference, potentially evading LTβR‐mediated antiviral immunity.
Single‐Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Small‐Cell Neuroendocrine Carcinoma of the Cervix
Authors: Chen Xinyi , Wang Kunyu , Liao Xingyu , Zheng Xingzheng , Yang Shuli , Han Chao , Lu Chang , Wang Xiaodan , Jin Lingge , Kang Haili , Han Yiding , Wei Jiacong , Fan Linyuan , Zhang Zhan , Kong Weimin
Published: January 2025

Small‐cell neuroendocrine cancer (SCNEC) of the uterine cervix is an exceedingly rare, highly aggressive tumor with an extremely poor prognosis. The cellular heterogeneity, origin, and tumorigenesis trajectories of SCNEC of the cervix remain largely unclear. We performed single‐cell RNA sequencing and whole‐exome sequencing on tumor tissues and adjacent normal cervical tissues from two patients diagnosed with SCNEC of the cervix. Here, we provide the first comprehensive insights into the cellular composition, HPV infection‐related features, and gene expression profiles of SCNEC of the cervix at single‐cell resolution. Correlation analyses suggested that SCNEC of the cervix may originate from squamous epithelial cells, and this observation was validated with bulk RNA‐seq data from external cervical neuroendocrine cancer. Furthermore, sex‐determining region Y‐box 2 (SOX2), a key transcription factor that functions in direct neural differentiation, was located in the copy number gain region and highly expressed in neuroendocrine tumor cells from both patients. Notable, the distributions of the HPV‐infected epithelium and SOX2 highly expressed epithelium were consistent with each other. Therefore, we supposed that high‐risk HPV infection and amplification of SOX2 in the squamous epithelium may contribute to the progression of small‐cell neuroendocrine tumorigenesis in the cervix.
Women's Participation in Operational and High Managerial Positions in Family Businesses: Evidence From Saudi Context
Authors: Khan Subuhi , Aloulou Wassim J. , Shahab Sana , Aliani Khaoula
Published: January 2025

This research explores the increasing participation of women in family businesses in Saudi Arabia, focusing on their roles in operational and high managerial positions within the context of Saudi Vision 2030. The research aims to fill the gap in understanding the profiles and drivers that encourage Saudi women to assume leadership roles in traditionally male‐dominated family businesses. Using a survey of 80 female participants, this study applies multiple correspondence analysis (MCA) and multinomial logistic regression (MLR) to explore the influence of factors such as education, sibling order, and family support on their advancement. The findings reveal that women's progression in family businesses is strongly linked to educational attainment and family backing, with significant emphasis on the growing support for women in the Kingdom in the last decade. While cultural and social barriers persist, there is a drastic shift in how women increasingly find opportunities for jobs and entrepreneurial ventures and contribute to the economy, even if in a smaller percentage than in other countries. The paper highlights that familial encouragement, higher education, and entrepreneurial spirit propel Saudi women to break through traditional limitations. Support from male family members, such as fathers or husbands, emerges as a critical driver that enables women to overcome traditional cultural barriers and assume leadership roles. The research also contributes to ongoing discussions about gender equality. It offers practical insights into creating supportive environments for women in leadership, thus fostering a more inclusive and diverse business landscape in Saudi Arabia. Additionally, the study draws attention to the importance of Saudi Vision 2030, which emphasizes women's empowerment and their economic contribution to eventually promoting gender equality and the advancement of the kingdom. This vision and various government initiatives, combined with increasing access to resources, social media, and digital platforms, open previously closed doors and present new opportunities for Saudi women to engage in business operations, particularly in fashion, healthcare, education, and retail. The findings are expected to inspire future research on women's leadership in the context of family businesses.
Extinction, Ultimate Boundedness, and Persistence in the Mean of a Stochastic Heroin Epidemic Model With Distributed Delay
Authors: Zhang Xiaofeng
Published: January 2025

In this paper, we consider a stochastic heroin epidemic model with distributed delay. We analyze the model in detail: We prove the existence and uniqueness of the global positive solution of the system, the asymptotic behavior around the equilibrium point of the deterministic system, the stochastically ultimate boundedness, and the persistence in the mean of the disease. Finally, we verify the main conclusions of this paper through numerical simulation and explore the influence of system parameters on the persistence and extinction of diseases. According to the numerical simulation results, we can give some suggestions on controlling diseases.
Deterministic, Stochastic, and Deep Learning Approaches to Understand the Economic Fluctuations in India
Authors: Karmakar Saptaporni , Chakraborty Arkaprovo
Published: January 2025

In the present work, a new mathematical framework is proposed for studying the interrelation among population growth rate, GDP, inflation rate, and unemployment rate within deterministic and stochastic frameworks. The values of the parameters of the proposed model are estimated using real data from India. The local and global uniqueness of solutions is established for the stochastic model. The deterministic model is solved by using the Adams‐Bashforth‐Moulton predictor‐corrector method, and Milstein's method is used for solving the stochastic model. Numerical simulations correlated quite strongly with observed data, while projections for the 2024–2030 period indicate that controlled population growth bodes well for the outlook of the economy for India, supporting economic prosperity alongside reduced inflation and better employment conditions. The findings presented in this work are correlational; therefore, to find the possible cause for this phenomenon, further research is required with detailed datasets. Comparing our model's GDP predictions with that obtained using a long short‐term memory recurrent neural network model returned very high values of predictive accuracy, thus reinforcing the strength and reliability of our framework.
Associations Between TCF7L2, PPARγ, and KCNJ11 Genotypes and Insulin Response to an Oral Glucose Tolerance Test: A Systematic Review
Authors: Blanken Carmen P. S. , Bayer Sandra , Buchner Carro Sophie , Hauner Hans , Holzapfel Christina
Published: January 2025

Scope: Insulin responses to standardized meals differ between individuals. This variability may in part be explained by genotype. This systematic review evaluates associations between genotype and insulin response to an oral glucose tolerance test (OGTT) in terms of insulin area under the curve (AUC). Methods and results: Three electronic databases (Web of Science, Embase, PubMed) were searched for studies investigating associations between insulin AUC after an OGTT and single nucleotide polymorphisms (SNPs) belonging to the transcription factor 7 like 2 (TCF7L2) gene, the peroxisome proliferator‐activated receptor gamma (PPARγ) gene, or the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene in persons without diabetes. A total of 5199 articles were identified, of which 38 were included. Among them were family‐based studies (9), twin studies (2), and studies with unrelated participants (27). Seventeen articles investigated TCF7L2 (7 SNPs), 14 investigated PPARγ (1 SNP), and 8 investigated KCNJ11 (5 SNPs). For all investigated SNPs, at least half of the reports indicated no statistically significant association with postprandial insulin AUC. Conclusion: No evidence was found for associations between TCF7L2, PPARγ, and KCNJ11 genotypes and insulin AUC after an OGTT. Future studies should investigate the effect of genetic risk scores on postprandial insulin.
Scalar Auxiliary Variable (SAV) Stabilization of Implicit‐Explicit (IMEX) Time Integration Schemes for Non‐Linear Structural Dynamics
Authors: Kwon Sun‐Beom , Prakash Arun
Published: January 2025

Implicit‐explicit (IMEX) time integration schemes are well suited for non‐linear structural dynamics because of their low computational cost and high accuracy. However, the stability of IMEX schemes cannot be guaranteed for general non‐linear problems. In this article, we present a scalar auxiliary variable (SAV) stabilization of high‐order IMEX time integration schemes that leads to unconditional stability. The proposed IMEX‐BDFk‐SAV schemes treat linear terms implicitly using kth‐order backward difference formulas (BDFk) and non‐linear terms explicitly. This eliminates the need for iterations in non‐linear problems and leads to low computational costs. Truncation error analysis of the proposed IMEX‐BDFk‐SAV schemes confirms that up to kth‐order accuracy can be achieved and this is verified through a series of convergence tests. Unlike existing SAV schemes for first‐order ordinary differential equations (ODEs), we introduce a novel SAV for the proposed schemes that allows direct solution of the second‐order ODEs without transforming them into a system of first‐order ODEs. Finally, we demonstrate the performance of the proposed schemes by solving several non‐linear problems in structural dynamics and show that the proposed schemes can achieve high accuracy at a low computational cost while maintaining unconditional stability.
A Crack‐Length Control Technique for Phase‐Field Fracture in FFT Homogenization
Authors: Aranda Pedro , Segurado Javier
Published: January 2025

Modeling the propagation of cracks at the microscopic level is fundamental to understand the effect of the microstructure on the fracture process. Nevertheless, microscopic propagation is often unstable and when using phase‐field fracture poor convergence is found or, in the case of using staggered algorithms, leads to the presence of jumps in the evolution of the cracks. In this work, a novel method is proposed to perform micromechanical simulations with phase‐field fracture imposing monotonic increases of crack length and allowing the use of monolithic implementations, being able to resolve all the snap‐backs during the unstable propagation phases. The method is derived for FFT‐based solvers in order to exploit its very high numerical performance in micromechanical problems, but an equivalent method is also developed for Finite Elements (FE) showing the equivalence of both implementations. It is shown that the stress‐strain curves and the crack paths obtained using the crack control method are superposed in stable propagation regimes to those obtained using strain control with a staggered scheme. J‐integral calculations confirm that during the propagation process in the crack control method, the energy release rate remains constant and equal to an effective fracture energy that has been determined as a function of the concretization for FFT simulations. Finally, to show the potential of the method, the technique is applied to simulate crack propagation through the microstructure of composites and porous materials providing an estimation of the effective fracture toughness.
A Novel ADI‐Weak Galerkin Method for Singularly Perturbed Two‐Parameter 2D Parabolic Pdes
Authors: Raina Aayushman , Natesan Srinivasan , Toprakseven Şuayip
Published: January 2025

In this article, we propose an Alternating Direction Implicit (ADI) type operator splitting weak Galerkin finite element method (WG‐FEM) for solving a parabolic singularly perturbed problem with two‐parameters in 2D over a layer‐adapted mesh. The suggested operator splitting approach divides the original model problem into two subproblems each in 1D, then solving each subproblem using WG‐FEM in spatial direction eventually reduces the computational difficulty and high storage requirements. Backward–Euler time discretization has been taken over a uniform mesh. Stability and convergence results have been proved for the fully‐discrete scheme. Numerical examples are presented corroborating in practice our theoretical findings.
The renin‐angiotensin‐aldosterone system and salt sensitivity of blood pressure offer new insights in obesity phenotypes
Authors: Yuan Yan Emily , Haas Andrea V. , Rosner Bernard , Williams Gordon H. , McDonnell Marie E. , Adler Gail K.
Published: January 2025

Objective

Individuals who have metabolically healthy overweight/obesity (MHOO) do not have cardiometabolic complications despite an elevated BMI. Renin‐angiotensin‐aldosterone system (RAAS) activation and salt sensitivity of blood pressure (SSBP) are cardiovascular disease (CVD) risks, which are increased in individuals with higher BMI values. Little is known about the differences in RAAS activation and SSBP between MHOO and metabolically unhealthy overweight/obesity (MUOO) phenotypes.

Methods

We studied 1430 adults on controlled dietary sodium. Individuals in the MHOO group had BMI ≥ 25 kg/m2 without comorbidities (e.g., diabetes, dyslipidemia, hypertension, CVD), whereas individuals in the MUOO group had BMI ≥ 25 kg/m2 and at least one comorbidity. The control group included healthy individuals (BMI 18.5–24.9 kg/m2).

Results

BMI was similar between the MHOO (28.9 kg/m2) and MUOO groups (29.3 kg/m2; p = 0.317). On liberal sodium, the MUOO group had activated RAAS compared with the MHOO group, including higher plasma aldosterone concentration (mean [SD], 1.11 [0.48] ng/dL; p = 0.020), plasma angiotensin II levels (4.11 [2.0] pg/mL; p = 0.040), and percentage of individuals with plasma renin activity ≥ 1.0 ng/mL/h (+3.6%; p = 0.017). The MUOO group had higher SSBP than the MHOO group (6.0 [1.9] mm Hg; p = 0.002). Applying a zero‐to‐six‐point metabolic health score found that a worse score was associated with higher measurements of RAAS activity and SSBP (p < 0.001).

Conclusions

Compared to the MHOO group, the MUOO group was characterized by an increase in the following two CVD risk factors: higher RAAS activity and SSBP on controlled sodium diets. Therapeutic interventions targeting the effects of angiotensin II and/or aldosterone may offer cardiometabolic protection for individuals with the MUOO phenotype.
Ionic Liquid Aided [11C]CO Fixation for Synthesis of 11C‐carbonyls
Authors: Lindberg Anton , Mokhtarinori Narges , Yang Zhenzhen , Dai Sheng , Popovs Ilja , Vasdev Neil
Published: January 2025

Tributyl(ethyl)phosphonium oxopentenolate ([P4442][Pen]) is an ionic liquid developed to capture CO and has shown ability to catalyze carbonylation reactions in organic chemistry. Carbon‐11 (11C, t1/2=20.4 min) labeled CO is a highly versatile building block for the synthesis of positron emission tomography (PET) radiotracers that are applied for medical imaging. The use of [11C]CO is limited by its low solubility in organic solvents. Herein, we report a proof‐of‐concept study evaluating a new method to prepare 11C‐labeled amides, ureas and carbamates via reaction of [11C]CO in [P4442][Pen] and applied for fully automated radiosyntheses of Bruton's tyrosine kinase inhibitors, [11C]evobrutinib and [11C]ibrutinib.
The Association of Physical Activity With Overweight/Obesity and Type 2 Diabetes in Nepalese Adults: Evidence From a Nationwide Non‐Communicable Disease Risk Factor Survey
Authors: Chimoriya Ritesh , Rana Kritika , Adhikari Jonas , Aitken Sarah J. , Poudel Prakash , Baral Aayush , Rawal Lal , Piya Milan K.
Published: January 2025

Background

The rising prevalence of obesity and type 2 diabetes (T2DM) is a significant public health concern, particularly in low‐ and middle‐income countries. This study aimed to explore the association between physical activity levels, overweight/obesity, and T2DM in a nationwide survey of Nepalese adults.

Methods

This was a secondary analysis of the 2019 non‐communicable diseases (NCD) risk factors STEPS survey conducted in Nepal. Demographic and anthropometric data, body mass index (BMI) and T2DM status were collected along with assessment of physical activity using Global Physical Activity Questionnaire (GPAQ). A two‐stage data analysis was conducted, first using descriptive statistics to summarize participant characteristics and differences across BMI and T2DM status, and then applying multivariate analyses to assess associations between physical activity levels, BMI and T2DM.

Results

Of the 5284 participants included, 28.0% had overweight/obesity, 5.8% had obesity, and 6.5% had T2DM. The mean age of the participants was 40.1 years (95% CI: 39.8–40.6), and 63.9% were female. The overall physical activity energy expenditure was higher in the lean group (BMI < 25 kg/m2) compared to the those with overweight/obesity, and among participants without T2DM compared to those with T2DM. Sedentary behavior was more common among individuals with overweight/obesity and T2DM. A higher proportion of participants with low physical activity was observed in the overweight/obesity group compared to the lean group (8.9% vs. 6.3%) and the T2DM group compared to the non‐T2DM group (11.7% vs. 6.7%). Low physical activity was associated with overweight/obesity (OR:1.4; 95% CI:1.1–1.8), obesity (OR:2.1; 95% CI:1.5–2.3), T2DM (OR:1.6; 95% CI:1.1–2.3) and T2DM in the presence of obesity (OR:3.6; 95% CI:1.7–7.8).

Conclusion

This study highlights the low rates of physical activity and higher rates of sedentary behavior among adults with overweight/obesity and T2DM in Nepal. Public health interventions promoting physical activity and reducing sedentary behavior may help reduce the burden of these NCDs.
Coblation Versus Radiofrequency for Tongue Base Reduction in Obstructive Sleep Apnea: A Meta‐analysis
Authors: Hussain Salman , Hayat Jafar , Chowdhury Raisa , Ebrahim Mahmoud , Alterki Abdulmohsen , Bahgat Ahmed , Al‐Sayed Ahmed A. , Padhye Vikram , Capasso Robson
Published: January 2025

Objective

The objective of this study is to determine the effectiveness and safety profile of coblation tongue base reduction (CBTR) compared to radiofrequency base of tongue (RFBOT) reduction on sleep‐related outcomes in patients with obstructive sleep apnea (OSA).

Data Sources

PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews databases.

Review Methods

Literature search by 2 independent authors was conducted using the abovementioned databases. Studies on CBTR and RFBOT as part of OSA treatment in adult patients with pre‐ and postoperative apnea–hypopnea index (AHI) were included. Direct meta‐analysis and single‐arm meta‐analysis were conducted to compare sleep‐related outcomes (AHI, apnea index [AI], surgical success rates, Epworth sleepiness score [ESS], SpO2, body mass index [BMI], and visual analog scale [VAS]) between both groups.

Results

A total of 40 studies with a total of 1940 patients were included, of which 1440 individuals who underwent tongue base reduction interventions (RF = 306, RF + UPPP = 656, and coblation + UPPP = 482) met inclusion criteria. Pooled analysis showed significant improvements in AHI (CBTR = −22.84, RFBOT = −11.14), AI (CBTR = 15.64, RFBOT = −5.26), ESS (CBTR = −7.59, RFBOT = −7.18), mean oxygen saturation (CBTR = 7.43, RFBOT = 4.25), mean BMI (CBTR = −0.69, RFBOT = −4.09), and snoring visual analog scale (CBTR = −16.20, RFBOT = −18.21). Surgical success rate (postoperative AHI < 20 and drop >50% from baselines) was 70% for CBTR and 43% for RFBOT.

Conclusion

Both interventions decreased sleep‐related outcomes in adult patients with OSA. Coblation appears to exhibit superiority over radiofrequency with a similar safety profile. However, further studies with direct comparisons between both interventions must be performed.
CHIT1 regulates the neuroinflammation and phagocytosis of microglia and suppresses Aβ plaque deposition in Alzheimer's disease
Authors: Yuan Shiyun , Zhong Fuxin , Wan Tianchi , Qin Zhangjin , Chen Lihua , Xing Dianxia , Zhang Wenbo , Yu Wuhan , Huang Lihong , Song Jiaqi , Yu Weihua , Lü Yang
Published: January 2025

Chitinase 1 (CHIT1), as a chitin‐specific hydrolase, significantly influences the progression of Alzheimer's disease (AD) through microglia‐associated inflammation and amyloid beta (Aβ) plaque accumulation. However, the precise mechanism of CHIT1 action in AD remains uncertain. The effects of CHIT1 on cerebral blood flow (CBF), hippocampal volume, and cognitive function were investigated in APP/PS1 mice. Protein alterations resulting from CHIT1 overexpression were analyzed using four‐dimensional (4D) label‐free quantitative (LFQ) protein spectrometry. Additionally, the influence of CHIT1 on microglial electrophysiology was assessed using patch clamp measurements, and its effects on neuroinflammation, phagocytosis, microglia migration, and neuronal apoptosis under AD‐like conditions were examined using the cell lines N9, BV‐2, and HT‐22. CHIT1 ameliorated hippocampal atrophy, hypoperfusion, and cognitive function deficits in the APP/PS1 mouse. CHIT1 regulates microglial function and neuronal protection through its interactions in AD. Increased levels of CHIT1/IDH1 contributed to an anti‐inflammatory phenotype in microglia via the Ca2+‐activated K+ channel, enhanced microglial phagocytosis, and promoted Aβ clearance. Conversely, knocking down IDH1 reduced the secretion of anti‐inflammatory agents and increased the production of inflammatory factors, as well as diminishing the expression of phagocytic factors and inhibiting Aβ endocytosis. Moreover, CHIT1 reduced neuronal apoptosis by diminishing the expression of apoptotic factors. However, IDH1 knockdown abrogated the protective effect of CHIT1 on neurons. CHIT1 exerts a protective role in AD pathogenesis through its interaction with IDH1. The CHIT1/IDH1 pathway promotes Aβ clearance via a shift in microglia toward an anti‐inflammatory state and prevents neuronal apoptosis and dysfunction caused by Aβ toxicity. © 2025 The Pathological Society of Great Britain and Ireland.
The Influence of Postmenstrual Age and Neurological Impairments on the Modified Pain Assessment Tool Score in Infants Admitted to Neonatal Intensive Care: A Retrospective Medical Record Review
Authors: Murray Jamie , Lam Jeremy , Jyoti Jeewan , Spence Kaye , Popat Himanshu , Ilhan Emre
Published: January 2025

Repetitive and prolonged experience of pain by infants in neonatal intensive care units (NICUs) may adversely affect growth and alter pain responses. The degree of infant prematurity and/or presence of neurological impairment (NI) may impact an infant's ability to behaviorally respond to pain. This study aimed to determine whether the scores on the mPAT, a widely used pain assessment tool, is impacted by postmenstrual age (PMA) at assessment, irrespective of neurological impairment. Data from medical records were collected on infants admitted to the NICU who underwent a pain assessment with the modified Pain Assessment Tool (mPAT) between March 2019 and September 2021. Total mPAT, behavioral, and physiological pain scores were independently analyzed using logistic regression to detect differences based on PMA categories (< 33 weeks, 33–36 weeks, ≥ 37 weeks) and presence of NI. Significant differences were indicated when p < 0.05. Of 204 infants sampled, 62% were male, and 71% were born at term‐age (i.e., ≥ 37 wks). Thirty‐six (18%) infants had a queried or confirmed NI and 28 (14%) infants were postsurgical. Logistic regression analysis showed that neither PMA nor presence of NI predicted pain for total mPAT scores (χ2 (3) = 3.9, p > 0.05) or physiological scores (χ2 (3) = 2.7, p > 0.05). Higher behavioral scores were 3.7 times (OR 0.27, 95% CI 0.10–0.77, p = 0.01) more likely in extremely‐to‐very preterm (< 33 weeks) infants when compared to term (≥ 37 weeks) infants. The mPAT may be suitable for clinicians to utilize when assessing infants in NICUs regardless of PMA or NI status. The higher behavioral responses in younger infants require further investigation in a future prospective study.
Unmanned aerial vehicle phenotyping of agronomic and physiological traits in mungbean
Authors: Van Haeften Shanice , Smith Daniel , Robinson Hannah , Dudley Caitlin , Kang Yichen , Douglas Colin A. , Hickey Lee T. , Potgieter Andries , Chapman Scott , Smith Millicent R.
Published: January 2025

Mungbean is an important sub‐tropical legume crop grown across Asia, Africa, and Australia. Yield improvement is crucial for expanding production, but phenotyping important traits across diverse environments using current approaches is challenging, limiting the scale and complexity of information captured. High‐throughput phenotyping platforms offer a solution by rapidly screening traits at scale. This study deploys an unmanned aerial vehicle (UAV) platform to determine the potential of phenotyping a range of agronomic and physiological traits within a diverse mungbean population evaluated across three field trials. Three predictive data‐driven modeling approaches were undertaken to evaluate performance accuracy in predicting these traits: linear regression, stepwise regression, and partial least squares regression. Results show that using the geometric trait “coverage” as a proxy is most suitable for screening visual traits like early vigor. For functional traits (i.e., aboveground biomass), predictive data‐driven models demonstrate high accuracy during early‐ and mid‐canopy development stages (R2 0.79, root mean square error [RMSE] 4.08 and R2 0.8, RMSE 26.92, respectively), but accuracy declines in late‐canopy development (R2 0.33 and RMSE 43.15). Prediction accuracy can be optimized by using different modeling approaches at different stages during the transition from early‐ to mid‐canopy development as well as canopy closure. Similar findings were observed when examining the prediction models for the physiological trait, stomatal conductance (R2 0.69 and RMSE 0.10). These approaches are expected to enable breeders and researchers to incorporate UAV‐based phenotyping systems into mungbean improvement programs. Such approaches might be most efficiently used at scale if applied as part of a “real‐time” calibration approach.