bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning Algorithms for understanding the determinants of under-five Mortality
Authors: Saroj Rakesh Kumar , Yadav Pawan Kumar , Singh Rajneesh , Chilyabanyama Obvious.N. 
Published: September 2022

Abstract
Background
Under-five mortality is a matter of serious concern for child health as well as the social development of any country. The paper aimed to find the accuracy of machine learning models in predicting under-five mortality and identify the most significant factors associated with under-five mortality.

Method
The data was taken from the National Family Health Survey (NFHS-IV) of Uttar Pradesh. First, we used multivariate logistic regression due to its capability for predicting the important factors, then we used machine learning techniques such as decision tree, random forest, Naïve Bayes, K- nearest neighbor (KNN), logistic regression, support vector machine (SVM), neural network, and ridge classifier. Each model’s accuracy was checked by a confusion matrix, accuracy, precision, recall, F1 score, Cohen’s Kappa, and area under the receiver operating characteristics curve (AUROC). Information gain rank was used to find the important factors for under-five mortality. Data analysis was performed using, STATA-16.0, Python 3.3, and IBM SPSS Statistics for Windows, Version 27.0 software.

Result
By applying the machine learning models, results showed that the neural network model was the best predictive model for under-five mortality when compared with other predictive models, with model accuracy of (95.29% to 95.96%), recall (71.51% to 81.03%), precision (36.64% to 51.83%), F1 score (50.46% to 62.68%), Cohen’s Kappa value (0.48 to 0.60), AUROC range (93.51% to 96.22%) and precision-recall curve range (99.52% to 99.73%). The neural network was the most efficient model, but logistic regression also shows well for predicting under-five mortality with accuracy (94% to 95%)., AUROC range (93.4% to 94.8%), and precision-recall curve (99.5% to 99.6%). The number of living children, survival time, wealth index, child size at birth, birth in the last five years, the total number of children ever born, mother’s education level, and birth order were identified as important factors influencing under-five mortality.

Conclusion
The neural network model was a better predictive model compared to other machine learning models in predicting under-five mortality, but logistic regression analysis also shows good results. These models may be helpful for the analysis of high-dimensional data for health research.
Wild-type IDH1 inhibition enhances chemotherapy response in melanoma
Authors: Zarei Mehrdad , Hajihassani Omid , Hue Jonathan J. , Graor Hallie J. , Loftus Alexander W. , Rathore Moeez , Vaziri-Gohar Ali , Asara John M. , Winter Jordan M. , Rothermel Luke D. 
Published: September 2022

Abstract
Background
Alternative treatment strategies in melanoma beyond immunotherapy and mutation-targeted therapy are urgently needed. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme protects cancer cells under metabolic stress, including nutrient limited conditions in the tumor microenvironment. Specifically, IDH1 generates NADPH to maintain redox homeostasis and produces α-ketoglutarate to support mitochondrial function through anaplerosis. Herein, the role of wtIDH1 in melanoma is further explored.

Methods
The expression of wtIDH1 was determined by qRT-PCR, and Western blot in melanoma cell lines and the effect of wtIDH1 on metabolic reprogramming in melanoma was interrogated by LC-MS. The impact of wtIDH1 inhibition alone and in combination with chemotherapy was determined in cell culture and mouse melanoma models.

Results
Melanoma patients express higher levels of the wtIDH1 enzyme compared to normal skin tissue, and elevated wtIDH1 expression portends poor patient survival. Knockdown of IDH1 by RNA interference inhibited cell proliferation and migration under low nutrient levels. Suppression of IDH1 expression in melanoma also decreased NADPH and glutathione levels, resulting in increased reactive oxygen species. An FDA-approved inhibitor of mutant IDH1, ivosidenib (AG-120), exhibited potent anti-wtIDH1 properties under low magnesium and nutrient levels, reflective of the tumor microenvironment in natura. Thus, similar findings were replicated in murine models of melanoma. In light of the impact of wtIDH1 inhibition on oxidative stress, enzyme blockade was synergistic with conventional anti-melanoma chemotherapy in pre-clinical models.

Conclusions
These results demonstrate the clinical potential of wtIDH1 inhibition as a novel and readily available combination treatment strategy for patients with advanced and refractory melanoma.

Graphical Abstract
Schematic shows increased wild-type IDH1 expression and activity as an adaptive response to metabolic stress induced by chemotherapy.
Differences in characteristics between patients ≥ 65 and < 65 years of age with orthopaedic injuries after severe trauma
Authors: Slørdal Tora Julie , Brattebø Guttorm , Geisner Thomas , Kristoffersen Målfrid Holen 
Published: September 2022

Abstract
Aim
Many trauma patients have associated orthopaedic injuries at admission. The existing literature regarding orthopaedic trauma often focuses on single injuries, but there is a paucity of information that gives an overview of this group of patients. Our aim was to describe the differences in characteristics between polytrauma patients ≥ 65 and < 65 years of age suffering orthopaedic injuries.

Methods
Patients registered in the Norwegian Trauma Registry (NTR) with an injury severity score (ISS) > 15 and orthopaedic injuries, who were admitted to Haukeland University Hospital in 2016–2018, were included. Data retrieved from the patients’ hospital records and NTR were analysed. The patients were divided into two groups based on age.

Results
The study comprised 175 patients, of which 128 (73%) and 47 (27%) were aged < 65 (Group 1) and ≥ 65 years (Group 2), respectively. The ISS and the new injury severity score (NISS) were similar in both groups. The dominating injury mechanism was traffic-related and thoracic injury was the most common location of main injury in both groups. The groups suffered a similar number of orthopaedic injuries. A significantly higher proportion of Group 1 underwent operative treatment for their orthopaedic injuries than in Group 2 (74% vs. 53%). The mortality in Group 2 was significantly higher than that in Group 1 (15% vs. 3%). In Group 2 most deaths were related to traffic injuries (71%). High energy falls and traffic-related incidents caused the same number of deaths in Group 1. In Group 1 abdominal injuries resulted in most deaths, while head injuries was the primary reason for deaths in Group 2.

Conclusions
Although the ISS and NISS were similar, mortality was significantly higher among patients aged ≥ 65 years compared to patients < 65 years of age. The younger age group underwent more frequently surgery for orthopaedic injuries than the elderly. There may be multiple reasons for this difference, but our study does not have sufficient data to draw any conclusions. Future studies may provide a deeper understanding of what causes treatment variation between age groups, which would hopefully help to further develop strategies to improve outcome for the elderly polytrauma patient.
The impact of interactive book sharing on child cognitive and socio-cognitive development (the REaL trial): study protocol for a randomized controlled trial
Authors: Forssman Linda , Gottwald Janna M. 
Published: September 2022

Abstract
Background
The quality of children’s early home learning environment has an influence on their cognitive development, preliteracy skills, and subsequent educational outcomes. Early intervention programs that promote positive parenting behaviors and child cognition have great potential to positively influence children’s school readiness and thereby support social equality. One often advocated parental practice for promoting child language and cognition is interactive book sharing.

Methods
We have conducted a randomized controlled trial to evaluate the effects of a parent-child interactive book sharing intervention on early child language, cognition, and parental behaviors. Participating caregivers and their 10-month-old child were randomized to an interactive book sharing intervention group (n = 59) or to an active control group (n = 56). The intervention was delivered by a facilitator to small groups of parent-child dyads on a weekly basis over 5 weeks. The primary outcomes were child language and socio-cognition; secondary outcomes were child executive function and parental scaffolding, sensitivity and reciprocity during book sharing, and problem-solving tasks. Data were collected at baseline, post-intervention, and at 6 and 12 months post-intervention.

Discussion
The Roadmap to Executive function and Language (REaL) trial aims to evaluate the impact of a brief early parenting intervention on key factors for child development, including child cognition and parental behaviors. If this intervention is beneficial for child outcomes, that would be of significance for the development of early interventions to promote child development.

Trial registration
The REaL trial is registered on the International Standard Randomized Controlled Trial Number database, registration number ISRCTN22319305. Retrospectively registered on 7 February 2020.
A novel 2B4 receptor leads to worse pregnancy outcomes by facilitating TNF-α and IFN-γ production in dNK cells during Toxoplasma gondii infection
Authors: Xu Xiaoyan , Zheng Guangmei , Ren Yushan , He Xiaohua , Peng Biwen , Hu Xuemei , Liu Wanhong 
Published: September 2022

AbstractBackgroundInfections are a major threat to human reproductive health because they can induce pregnancy failure, including recurrent abortion, stillbirth, and preterm birth.Toxoplasma gondii(T. gondii) infection can result in adverse pregnancy outcomes by affecting certain immune molecules and cytokines. However, the detailed mechanisms behindT. gondii-induced pregnancy failure are poorly understood.MethodsToxoplasma gondii-infected wild-type (WT) pregnant mice and 2B4 knockout (2B4−/−) pregnant mice were established for in vivo study. Human decidual natural killer (dNK) cells were cultured for in vitro study. Abnormal pregnancy outcomes were observed, and the expression of 2B4, functional molecules (CD69, CD107a, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), and signaling molecules (SHP-2, Fyn, p-ERK, p-P38) in dNK cells were detected by flow cytometry, Western blot, reverse transcriptase polymerase chain reaction (RT-PCR), and/or immunofluorescence. The direct interactions (2B4 interacts with SHP-2 and Fyn; SHP-2 interacts with p-P38 and 2B4; Fyn interacts with p-ERK and 2B4) were verified by co-immunoprecipitation (co-IP) in NK-92 cells.ResultsHere, results showed that 2B4 was significantly downregulated afterT. gondiiinfection. Subsequently, infected 2B4−/−pregnant mice displayed worse pregnancy outcomes compared with infected WT pregnant mice. Also, increased TNF-α and IFN-γ expression and elevated dNK cell cytotoxicity were found in 2B4−/−pregnant mice duringT. gondiiinfection. In contrast, reduced TNF-α and IFN-γ expression and decreased human dNK cell activity were found following 2B4 activation duringT. gondiiinfection. Interestingly, results showed that 2B4 binds to adaptor SHP-2 or Fyn, which then triggers different signaling pathways to regulate TNF-α and IFN-γ expression in dNK cells duringT. gondiiinfection. Further, SHP-2 binds 2B4 and p-P38 directly after 2B4 activation, which generates an inhibitory signal for TNF-α and IFN-γ in NK-92 cells. In addition, Fyn can bind to 2B4 and p-ERK after activation of 2B4, thereby inhibiting TNF-α and IFN-γ expression in NK-92 cells followingT. gondiiinfection.ConclusionsThese data suggest that 2B4 may be a novel danger-signaling molecule that is implicated in pregnancy failure duringT. gondiiinfection. Unraveling the mechanism by which 2B4 regulates dNK cell activity will provide novel insights to aid our understanding ofT. gondii-induced adverse pregnancy outcomes.Graphical Abstract
Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination
Authors: Rosen Sarah F. , Soung Allison L. , Yang Wei , Ai Shenjian , Kanmogne Marlene , Davé Veronica A. , Artyomov Maxim , Magee Jeffrey A. , Klein Robyn S. 
Published: September 2022

Abstract
Background
Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS-resident memory T (TRM) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown.

Methods
Here, we examined immune cells within the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation and genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss.

Results
Profiling of host transcriptome immune cells at 25 days post-infection in mice revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in TRM cell biology, was identified as critically regulating CXCR6 expressing CD8+ TRM cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highly expressed by all myeloid cells, and its unique receptor, CXCR6, is highly expressed on all CD8+ T cells. Using genetic and pharmacological approaches, we demonstrate that CXCL16/CXCR6 not only is required for the maintenance of WNV-specific CD8 TRM cells in the post-infectious CNS, but also contributes to their expression of TRM cell markers. Moreover, CXCR6+CD8+ T cells are required for glial activation and ongoing synapse elimination.

Conclusions
We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8+ T cells that maintains forebrain TRM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 in mice during recovery may reduce CNS CD8+ TRM cells.
Reduced gut microbiota diversity in patients with congenital generalized lipodystrophy
Authors: Montenegro Junior Renan Magalhães , Ponte Clarisse Mourão Melo , Castelo Maria Helane Costa Gurgel , de Oliveira Silveira Alessandro Conrado , Fernandes Virgínia Oliveira , D’Alva Catarina Brasil , Oliveira Luiz Felipe Valter , Hristov Angélica Domingues , Bandeira Silviane Praciano , da Cruz Paiva Grayce Ellen , Levi José Eduardo 
Published: September 2022

Abstract
Background
Previous studies suggest intestinal dysbiosis is associated with metabolic diseases. However, the causal relationship between them is not fully elucidated. Gut microbiota evaluation of patients with congenital generalized lipodystrophy (CGL), a disease characterized by the absence of subcutaneous adipose tissue, insulin resistance, and diabetes since the first years of life, could provide insights into these relationships.

Methods
A cross-sectional study was conducted with patients with CGL (n = 17) and healthy individuals (n = 17). The gut microbiome study was performed by sequencing the 16S rRNA gene through High-Throughput Sequencing (BiomeHub Biotechnologies, Brazil).

Results
The median age was 20.0 years old, and 64.7% were female. There was no difference between groups in pubertal stage, BMI, ethnicity, origin (rural or urban), delivery, breastfeeding, caloric intake, macronutrient, or fiber consumption. Lipodystrophic patients presented a lower alpha diversity (Richness index: 54.0 versus 67.5; p = 0.008). No differences were observed in the diversity parameters when analyzing the presence of diabetes, its complications, or the CGL subtype.

Conclusion
In this study, we demonstrate for the first time a reduced gut microbiota diversity in individuals with CGL. Dysbiosis was present despite dietary treatment and was also observed in young patients. Our findings allow us to speculate that the loss of intestinal microbiota diversity may be due to metabolic abnormalities present since the first years of life in CGL. Longitudinal studies are needed to confirm these findings, clarifying the possible causal link between dysbiosis and insulin resistance in humans.
The failure of success: four lessons learned in five years of research on research integrity and research assessments
Authors: Aubert Bonn Noémie , De Vries Raymond G. , Pinxten Wim 
Published: September 2022

AbstractIn the past 5 years, we captured the perspectives from a broad array of research stakeholders to better understand the impact that current approaches to success and research assessment may have on the integrity and the quality of research. Here, we translate our findings in four actions that are urgently needed to foster better research. First, we need to address core research structures to overcome systemic problems of the research enterprise; second, we must realign research assessments to value elements that advance and strengthen science; third, we need to remodel, diversify, and secure research careers; and finally, we need to unite and coordinate efforts for change.
Does shift-and-persist strategy buffer career choice anxiety and affect career exploration?
Authors: Lee Sumin , Kobayashi Ryota , Oda Mami , Noritake Yoshihide , Nakashima Ken’ichiro 
Published: September 2022

Abstract
Objective
The transition from school to the workforce is important for concrete future planning. During this period, people are more likely to experience psychological health problems, such as anxiety and feelings of hopelessness and helplessness. In particular, job hunting in individuals with low socioeconomic status (SES) leads to various impulsive behaviors and physical and psychological problems due to a scarcity of economic and time resources. There is a lack of research examining career education and intervention approaches that consider the backgrounds of those experiencing adversities and difficulties due to low SES. Considering these situations, we examined whether shift-and-persist coping strategies (S-P) could buffer the career choice anxiety of individuals with low SES and improve career exploration.

Results
The results from 311 students who preparing/doing for job hunting showed a negative association between S-P and career choice anxiety and a positive association with career exploration. There are no significant effects of the direct link between SES to career exploration and the indirect link between SES and career exploration via career choice anxiety. There was also no buffering effect of S-P use on the above mediating process.
Atypical gaze patterns in autistic adults are heterogeneous across but reliable within individuals
Authors: Keles Umit , Kliemann Dorit , Byrge Lisa , Saarimäki Heini , Paul Lynn K. , Kennedy Daniel P. , Adolphs Ralph 
Published: September 2022

AbstractBackgroundAcross behavioral studies, autistic individuals show greater variability than typically developing individuals. However, it remains unknown to what extent this variability arises from heterogeneity across individuals, or from unreliability within individuals. Here, we focus on eye tracking, which provides rich dependent measures that have been used extensively in studies of autism. Autistic individuals have an atypical gaze onto both static visual images and dynamic videos that could be leveraged for diagnostic purposes if the above open question could be addressed.MethodsWe tested three competing hypotheses: (1) that gaze patterns of autistic individuals are less reliable or noisier than those of controls, (2) that atypical gaze patterns are individually reliable but heterogeneous across autistic individuals, or (3) that atypical gaze patterns are individually reliable and also homogeneous among autistic individuals. We collected desktop-based eye tracking data from two different full-length television sitcom episodes, at two independent sites (Caltech and Indiana University), in a total of over 150 adult participants (N = 48 autistic individuals with IQ in the normal range, 105 controls) and quantified gaze onto features of the videos using automated computer vision-based feature extraction.ResultsWe found support for the second of these hypotheses. Autistic people and controls showed equivalently reliable gaze onto specific features of videos, such as faces, so much so that individuals could be identified significantly above chance using a fingerprinting approach from video epochs as short as 2 min. However, classification of participants into diagnostic groups based on their eye tracking data failed to produce clear group classifications, due to heterogeneity in the autistic group.LimitationsThree limitations are the relatively small sample size, assessment across only two videos (from the same television series), and the absence of other dependent measures (e.g., neuroimaging or genetics) that might have revealed individual-level variability that was not evident with eye tracking. Future studies should expand to larger samples across longer longitudinal epochs, an aim that is now becoming feasible with Internet- and phone-based eye tracking.ConclusionsThese findings pave the way for the investigation of autism subtypes, and for elucidating the specific visual features that best discriminate gaze patterns—directions that will also combine with and inform neuroimaging and genetic studies of this complex disorder.
The SP-ET index is a new index for assessing the vertical position of patella
Authors: Li Jia , Yuan Mao , Qiu Lanyu , Sheng Bo , Yu Fan , Yang Haitao , Lv Furong , Lv Fajin , Huang Wei 
Published: September 2022

Abstract
Background
Some parameters in previous studies did not better reflect the vertical position of the patella relative to the femoral trochlear. This study aimed to assess the value of the most superior point of patella-entrance of femoral trochlea distance ratio (SP-ET index) as a newer index in defining the vertical position of patella relative to the trochlea, correlate it with the Insall–Salvati ratio, and investigate the effect of the new index on patellar cartilage lesions.

Methods
A total of 99 knees of 77 patients with patellar cartilage lesions were retrospectively analyzed using magnetic resonance imaging (MRI) data. The Insall–Salvati ratio and SP-ET index were measured on MR images. Ninety-nine knees just with meniscus rupture were enrolled as the control group. The two parameters of the patellar cartilage lesions were compared with those of the control group.

Results
The Insall–Salvati ratio and SP-ET index in the patellar cartilage lesions group were significantly higher than those in the control group (p < 0.001). The SP-ET index showed a moderate positive correlation with the Insall–Salvati ratio (r = 0.307, p < 0.001). Receiver operating characteristic (ROC) analysis showed that the diagnostic efficiency of the SP-ET index was better than that of the Insall–Salvati ratio in patients with patellar cartilage lesions.

Conclusion
The SP-ET index may be a useful complement parameter to define the vertical position of the patella relative to the femoral trochlear. Increased SP-ET index may be an important risk factor for patellar cartilage lesions.