bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and molecular description of the first Italian cohort of 33 subjects with hypophosphatasia
Authors: Cinque Luigia , Pugliese Flavia , Salcuni Antonio Stefano , Trombetta Domenico , Battista Claudia , Biagini Tommaso , Augello Bartolomeo , Nardella Grazia , Conti Francesco , Corbetta Sabrina , Fischetto Rita , Foiadelli Thomas , Gaudio Agostino , Giannini Cosimo , Grosso Enrico , Guabello Gregorio , Massuras Stefania , Palermo Andrea , Politano Luisa , Pigliaru Francesca , Ruggeri Rosaria Maddalena , Scarano Emanuela , Vicchio Piera , Cannavò Salvatore , Celli Mauro , Petrizzelli Francesco , Mastroianno Mario , Castori Marco , Scillitani Alfredo , Guarnieri Vito 
Published: August 2023

IntroductionHypophosphatasia (HPP) is a rare genetic disease caused by inactivating variants of the ALPL gene. Few data are available on the clinical presentation in Italy and/or on Italian HPP surveys.MethodsThere were 30 suspected HPP patients recruited from different Italian tertiary cares. Biological samples and related clinical, biochemical, and anamnestic data were collected and the ALPL gene sequenced. Search for large genomic deletions at the ALPL locus (1p36) was done. Phylogenetic conservation and modeling were applied to infer the effect of the variants on the protein structure.ResultsThere were 21 ALPL variants and one large genomic deletion found in 20 out of 30 patients. Unexpectedly, NGS-driven differential diagnosis allowed uncovering three hidden additional HPP cases, for a total of 33 HPP subjects. Eight out of 24 coding variants were novel and classified as “pathogenic”, “likely pathogenic”, and “variants of uncertain significance”. Bioinformatic analysis confirmed that all the variants strongly destabilize the homodimer structure. There were 10 cases with low ALP and high VitB6 that resulted negative to genetic testing, whereas two positive cases have an unexpected normal ALP value. No association was evident with other biochemical/clinical parameters.DiscussionWe present the survey of HPP Italian patients with the highest ALPL mutation rate so far reported and confirm the complexity of a prompt recognition of the syndrome, mostly for HPP in adults. Low ALP and high VitB6 values are mandatory for the genetic screening, this latter remaining the gold standard not only to confirm the clinical diagnosis but also to make differential diagnosis, to identify carriers, to avoid likely dangerous therapy in unrecognized cases.
Neuropilin 2 in osteoblasts regulates trabecular bone mass in male mice
Authors: Verlinden Lieve , Doms Stefanie , Janssens Iris , Meyer Mark B. , Pike J. Wesley , Carmeliet Geert , Verstuyf Annemieke 
Published: August 2023

IntroductionNeuropilin 2 (NRP2) mediates the effects of class 3 semaphorins and vascular endothelial growth factor and is implicated in axonal guidance and angiogenesis. Moreover, NRP2 expression is suggested to be involved in the regulation of bone homeostasis. Indeed, osteoblasts and osteoclasts express NRP2 and male and female global Nrp2 knockout mice have a reduced bone mass accompanied by reduced osteoblast and increased osteoclast counts.MethodsWe first examined the in vitro effect of the calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on Nrp2 transcription in osteoblasts. We next generated mice with a conditional deletion of Nrp2 in the osteoblast cell lineage under control of the paired related homeobox 1 promoter and mice with a conditional Nrp2 knockdown in osteoclasts under control of the Lysozyme promoter. Mice were examined under basal conditions or after treatment with either the bone anabolic vitamin D3 analog WY 1048 or with 1,25(OH)2D3.Results and discussionWe show that Nrp2 expression is induced by 1,25(OH)2D3 in osteoblasts and is associated with enrichment of the vitamin D receptor in an intronic region of the Nrp2 gene. In male mice, conditional deletion of Nrp2 in osteoblast precursors and mature osteoblasts recapitulated the bone phenotype of global Nrp2 knockout mice, with a reduced cortical cross-sectional tissue area and lower trabecular bone content. However, female mice with reduced osteoblastic Nrp2 expression display a reduced cross-sectional tissue area but have a normal trabecular bone mass. Treatment with the vitamin D3 analog WY 1048 (0.4 μg/kg/d, 14 days, ip) resulted in a similar increase in bone mass in both genotypes and genders. Deleting Nrp2 from the osteoclast lineage did not result in a bone phenotype, even though in vitro osteoclastogenesis of hematopoietic cells derived from mutant mice was significantly increased. Moreover, treatment with a high dose of 1,25(OH)2D3 (0.5 μg/kg/d, 6 days, ip), to induce osteoclast-mediated bone resorption, resulted in a similar reduction in trabecular and cortical bone mass. In conclusion, osteoblastic Nrp2 expression is suggested to regulate bone homeostasis in a sex-specific manner.
The predictive values of admission characteristics for 28-day all-cause mortality in septic patients with diabetes mellitus: a study from the MIMIC database
Authors: Yang Chengyu , Jiang Yu , Zhang Cailin , Min Yu , Huang Xin 
Published: August 2023

BackgroundSeptic patients with diabetes mellitus (DM) are more venerable to subsequent complications and the resultant increase in associated mortality. Therefore, it is important to make tailored clinical decisions for this subpopulation at admission.MethodData from large-scale real-world databases named the Medical Information Mart for Intensive Care Database (MIMIC) were reviewed. The least absolute selection and shrinkage operator (LASSO) was performed with 10 times cross-validation methods to select the optimal prognostic factors. Multivariate COX regression analysis was conducted to identify the independent prognostic factors and nomogram construction. The nomogram was internally validated via the bootstrapping method and externally validated by the MIMIC III database with receiver operating characteristic (ROC), calibration curves, decision curve analysis (DCA), and Kaplan-Meier curves for robustness check.ResultsA total of 3,291 septic patients with DM were included in this study, 2,227 in the MIMIC IV database and 1,064 in the MIMIC III database, respectively. In the training cohort, the 28-day all-cause mortality rate is 23.9% septic patients with DM. The multivariate Cox regression analysis reveals age (hazard ratio (HR)=1.023, 95%CI: 1.016-1.031, p&lt;0.001), respiratory failure (HR=1.872, 95%CI: 1.554-2.254, p&lt;0.001), Sequential Organ Failure Assessment score (HR=1.056, 95%CI: 1.018-1.094, p=0.004); base excess (HR=0.980, 95%CI: 0.967-0.992, p=0.002), anion gap (HR=1.100, 95%CI: 1.080-1.120, p&lt;0.001), albumin (HR=0.679, 95%CI: 0.574-0.802, p&lt;0.001), international normalized ratio (HR=1.087, 95%CI: 1.027-1.150, p=0.004), red cell distribution width (HR=1.056, 95%CI: 1.021-1.092, p=0.001), temperature (HR=0.857, 95%CI: 0.789-0.932, p&lt;0.001), and glycosylated hemoglobin (HR=1.358, 95%CI: 1.320-1.401, p&lt;0.001) at admission are independent prognostic factors for 28-day all-cause mortality of septic patients with DM. The established nomogram shows satisfied accuracy and clinical utility with AUCs of 0.870 in the internal validation and 0.830 in the external validation cohort as well as 0.820 in the septic shock subpopulation, which is superior to the predictive value of the single SOFA score.ConclusionOur results suggest that admission characteristics show an optimal prediction value for short-term mortality in septic patients with DM. The established model can support intensive care unit physicians in making better initial clinical decisions for this subpopulation.
Impaired Abcb1a function and red meat in a translational colitis mouse model induces inflammation and alters microbiota composition
Authors: Stensballe Allan , Bennike Tue Bjerg , Ravn-Haren Gitte , Mortensen Alicja , Aboo Christopher , Knudsen Lina Almind , Rühlemann Malte C. , Birkelund Svend , Bang Corinne , Franke Andre , Vogel Ulla , Hansen Axel Kornerup , Andersen Vibeke 
Published: August 2023

Inflammatory Bowel Disease (IBD) affects approximately 0.3% of the global population, with incidence rates rising dramatically worldwide. Emerging evidence points to an interplay between exposome factors such as diet and gut microbiota, host genetics, and the immune system as crucial elements in IBD development. ATP-binding cassette (ABC) transporters, including human p-glycoprotein encoded by the Abcb1 gene, influence intestinal inflammation, and their expression may interact with environmental factors such as diet and gut microbes. Our study aimed to examine the impact of protein sources on a genetic colitis mouse model.MethodsAbcb1a-deficient colitis mice were fed either casein or red meat-supplemented diets to investigate potential colitis-aggravating components in red meat and their effects on host-microbiota interactions. We conducted deep label free quantitative proteomic inflammation profiling of gastrointestinal tissue (colon, ileum) and urine, and determined the overall microbiome in feces using 16S rRNA gene sequencing. Microbiota shifts by diet and protein transporter impairment were addressed by multivariate statistical analysis. Colon and systemic gut inflammation were validated through histology and immune assays, respectively.ResultsA quantitative discovery based proteomic analysis of intestinal tissue and urine revealed associations between ileum and urine proteomes in relation to Abcb1a deficiency. The absence of Abcb1a efflux pump function and diet-induced intestinal inflammation impacted multiple systemic immune processes, including extensive neutrophil extracellular trap (NET) components observed in relation to neutrophil degranulation throughout the gastrointestinal tract. The colitis model’s microbiome differed significantly from that of wild-type mice, indicating the substantial influence of efflux transporter deficiency on microbiota.ConclusionThe proteomic and microbiota analyzes of a well-established murine model enabled the correlation of gastrointestinal interactions not readily identifiable in human cohorts. Insights into dysregulated biological pathways in this disease model might offer translational biomarkers based on NETs and improved understanding of IBD pathogenesis in human patients. Our findings demonstrate that drug transporter deficiency induces substantial changes in the microbiota, leading to increased levels of IBD-associated strains and resulting in intestinal inflammation.GRAPHICAL ABSTRACT
SSVEP unsupervised adaptive feature recognition method based on self-similarity of same-frequency signals
Authors: Yan Wenqiang , He Bo , Zhao Jin 
Published: August 2023

IntroductionAs an important human-computer interaction technology, steady-state visual evoked potential (SSVEP) plays a key role in the application of brain computer interface (BCI) systems by accurately decoding SSVEP signals. Currently, the majority SSVEP feature recognition methods use a static classifier. However, electroencephalogram (EEG) signals are non-stationary and time-varying. Hence, an adaptive classification method would be an alternative option to a static classifier for tracking the changes in EEG feature distribution, as its parameters can be re-estimated and updated with the input of new EEG data.MethodsIn this study, an unsupervised adaptive classification algorithm is designed based on the self-similarity of same-frequency signals. The proposed classification algorithm saves the EEG data that has undergone feature recognition as a template signal in accordance with its estimated label, and the new testing signal is superimposed with the template signals at each stimulus frequency as the new test signals to be analyzed. With the continuous input of EEG data, the template signals are continuously updated.ResultsBy comparing the classification accuracy of the original testing signal and the testing signal superimposed with the template signals, this study demonstrates the effectiveness of using the self-similarity of same-frequency signals in the adaptive classification algorithm. The experimental results also show that the longer the SSVEP-BCI system is used, the better the responses of users on SSVEP are, and the more significantly the adaptive classification algorithm performs in terms of feature recognition. The testing results of two public datasets show that the adaptive classification algorithm outperforms the static classification method in terms of feature recognition.DiscussionThe proposed adaptive classification algorithm can update the parameters with the input of new EEG data, which is of favorable impact for the accurate analysis of EEG data with time-varying characteristics.
Predicting weight loss success on a new Nordic diet: an untargeted multi-platform metabolomics and machine learning approach
Authors: Pigsborg Kristina , Stentoft-Larsen Valdemar , Demharter Samuel , Aldubayan Mona Adnan , Trimigno Alessia , Khakimov Bekzod , Engelsen Søren Balling , Astrup Arne , Hjorth Mads Fiil , Dragsted Lars Ove , Magkos Faidon 
Published: August 2023

Background and aimResults from randomized controlled trials indicate that no single diet performs better than other for all people living with obesity. Regardless of the diet plan, there is always large inter-individual variability in weight changes, with some individuals losing weight and some not losing or even gaining weight. This raises the possibility that, for different individuals, the optimal diet for successful weight loss may differ. The current study utilized machine learning to build a predictive model for successful weight loss in subjects with overweight or obesity on a New Nordic Diet (NND).MethodsNinety-one subjects consumed an NND ad libitum for 26 weeks. Based on their weight loss, individuals were classified as responders (weight loss ≥5%, n = 46) or non-responders (weight loss &lt;2%, n = 24). We used clinical baseline data combined with baseline urine and plasma untargeted metabolomics data from two different analytical platforms, resulting in a data set including 2,766 features, and employed symbolic regression (QLattice) to develop a predictive model for weight loss success.ResultsThere were no differences in clinical parameters at baseline between responders and non-responders, except age (47 ± 13 vs. 39 ± 11 years, respectively, p = 0.009). The final predictive model for weight loss contained adipic acid and argininic acid from urine (both metabolites were found at lower levels in responders) and generalized from the training (AUC 0.88) to the test set (AUC 0.81). Responders were also able to maintain a weight loss of 4.3% in a 12 month follow-up period.ConclusionWe identified a model containing two metabolites that were able to predict the likelihood of achieving a clinically significant weight loss on an ad libitum NND. This work demonstrates that models based on an untargeted multi-platform metabolomics approach can be used to optimize precision dietary treatment for obesity.
The effect of maternal vitamin D deficiency during pregnancy on glycolipid metabolism of offspring rats and the improvement of vitamin D intervention after weaning
Authors: Chen Zhaojun , Zhu Yunxia , Wu Ting , Qian Xia , Hu Ye , Hu Wensheng 
Published: August 2023

BackgroundVitamin D deficiency during pregnancy is common, but whether maternal vitamin D status affects glycolipid metabolism of offspring remains unclear.ObjectiveTo evaluate the effect of maternal vitamin D deficiency during pregnancy on the glycolipid metabolism of offspring at different life-cycles (from birth to adulthood) and to explore the improvement of different dosages of vitamin D supplementation.MethodsSprague–Dawley rats were fed vitamin D-deprived (VDD group) or standard vitamin D diets (SC group) during pregnancy, and their diets were changed to standard vitamin D diets during lactation (the offspring were sorted into VDDoffspring and SCoffspring groups). After weaning, rats in the VDDoffspring group were randomly assigned to the VDDoffspring, VDDoffspring-S3300 and VDDoffspring-S10000 groups with diets containing standard, medium and high dosages of vitamin D for 12 wk. Serum was collected for biochemical analyses at postnatal Day 21, postnatal Day 56 and postnatal Day 84. Oral glucose tolerance test (OGTT) was performed at postnatal Day 70.ResultsCompared to SCoffspring, rats in the VDDoffspring group had significantly lower birth weight with faster weight gain and higher levels of lipid metabolism in early life. After near adulthood, the differences in weight and lipid metabolism between the two groups disappeared. OGTT showed significantly higher blood glucose levels in the VDDoffspring group at 30 min, 60 min, and 90 min. The continuation of vitamin D supplementation at medium and high dosages after weaning did not cause any obvious changes in weight or glycolipid metabolism (except for postprandial hyperglycemia). OGTT demonstrated that the glucose levels in the VDDoffspring-S3300 group were lowest at all the time points and that those in the VDDoffspring-S10000 group were the highest at 30 min, 60 min, and 90 min among the three groups.ConclusionThe adverse effects of vitamin D deficiency during pregnancy on glycolipid metabolism in offspring vary in different stages. Over a long time period, adequate vitamin D supplementation is beneficial to glycolipid metabolism for the offspring of subjects with vitamin D deficiency during pregnancy; however, further improvement is required.
Self-care in children and young people with complex chronic conditions: a qualitative study using Emotional Text Mining
Authors: Spitaletta Giuseppina , Biagioli Valentina , Greco Francesca , Mascolo Rachele , Liburdi Annachiara , Manzi Giulia , Gawronski Orsola , Ricci Riccardo , Tiozzo Emanuela , Vellone Ercole , Grimaldi Capitello Teresa , Salata Michele , Raponi Massimiliano , Dall’Oglio Immacolata ,   Self-care CYP Study Group
Published: August 2023

ObjectivesTo explore: (1) self-care behaviors in children and young people (range: 6 months–24 years) with complex chronic conditions, characterized by the diagnosis of a severe chronic condition, substantial family-identified needs, functional limitations associated with technology dependence, and intensive use of healthcare services; (2) the contribution to self-care of family members and other persons involved in the child's health and daily life context (e.g., health professionals and teachers), and (3) the principal factors that might have influenced the self-care process associated with developmental age.MethodsA qualitative descriptive study was conducted in an Italian academic tertiary pediatric hospital between September 2020 and May 2021. Overall, 25 focus groups and 7 online interviews were conducted via videoconferencing. Textual data were analyzed using Emotional Text Mining to identify three levels of communication: the factors, the main themes (clusters), and the sub-themes.ResultsA total of 104 participants were enrolled, including 27 patients with complex chronic conditions (12 males, mean age = 11.1 ± 4.40), 33 parents, 6 siblings, 33 health professionals, and 5 teachers. Participants described the process of self-care through four main factors: “self-care”, “external settings”, “family”, and “management”. Five clusters (themes) were identified: (1) Self-care management (device; consulting); (2) Shift of agency (influencing factors; parents; school); (3) Self-care support (normal life and personal development; multidisciplinary support); (4) Daily self-care maintenance/monitoring; (5) Treatment adherence. Self-care management was mostly relevant for parents of children aged between 6 months and 3 years.ConclusionThe self-care process varies according to the needs related to the specific developmental age and the evolution of the clinical condition over time. The contribution of the family, health professionals, and social networks is fundamental for adequate self-care. To help families manage the unstable condition of their children at home, it is necessary to strengthen support networks implement home care, and ensure continuity of care.
Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts aqueous extract mitigates cisplatin-induced nephrotoxicity via attenuation of inflammation, and DNA damage
Authors: Mufti Afoua , Feriani Anouar , Ouchari Wafae , Mandour Yasmine M. , Tlili Nizar , Ibrahim Mohammed Auwal , Mahmoud Mona F. , Sobeh Mansour 
Published: August 2023

Herein, we explored the protective effect of Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts extract (LO) against cisplatin (CP)-induced nephrotoxicity in rats and profiled their phytocontents. A total of 31 compounds belonging to organic and phenolic acids and their glycosides as well as flavonoids and their O- and C-glycosides were identified through LC-MS/MS. The DPPH and FRAP assays revealed that the extract had powerful antioxidant properties. The in vivo results demonstrated that administering LO extract for 30 days (40 and 80 mg/kg b. w.) significantly improved the altered renal injury markers via reducing creatinine (high dose only) and uric acid levels compared to the Cp-group. The deleterious action of cisplatin on renal oxidative stress markers (GSH, MDA, SOD, and CAT) were also mitigated by LO-pretreatment. The reduction of the inflammatory marker (IL-6), and inhibition of DNA fragmentation, highlighted the prophylactic action of LO in kidney tissue. Molecular docking followed by a 100 ns molecular dynamic simulation analyses revealed that, amongst the 31 identified compounds in LO, chlorogenic and caffeoylmalic acids had the most stable binding to IL-6. The nephroprotective effects were further confirmed by histopathological observations, which showed improvement in ultrastructural changes induced by cisplatin. The observed findings reinforce the conclusion that L. ocymifolia extract exerts nephroprotective properties, which could be related to its antioxidant and anti-inflammatory activities. Further studies are required to determine the therapeutic doses and the proper administration time.
Do applicants from Generation X, Y, Z differ in personality traits? data from selection procedures in aviation (1987–2019)
Authors: Stelling Dirk 
Published: August 2023

IntroductionThe objective of this study is to research personality trait differences across generations and the impact of age, gender and self-presentation on these traits.MethodsA total of 82,147 applicants (aged 17–24) for aviation training (pilot, air traffic controller), born between 1965 and 2002, were divided into three cohorts (Generation X, Y, Z). We analysed data from the temperament structure scales (TSS) personality questionnaire, which was collected during selection procedures between 1987 and 2019. Generational differences were analysed by ANCOVAs with generation and gender as group factors, controlled by age and self-presentation (social desirability).ResultsAge had no significant impact, but we observed slight gender differences in emotional stability, vitality, empathy, and self-presentation across all generations. The generational differences found exhibited extremely small effect sizes, suggesting that applicants have become more extraverted, controlled (with lower aggression and higher rigidity), and inclined to present themselves in a more favourable manner.DiscussionWe discuss the implications of these findings for the aviation industry and the applicability of Generation theory in personality trait research.