bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nontuberculous mycobacterium could solve the mystery of the lady from the Franciscan church in Basel, Switzerland
Authors: Sarhan Mohamed S. , Wurst Christina , Tzankov Alexandar , Bircher Andreas J. , Wittig Holger , Briellmann Thomas , Augsburger Marc , Hotz Gerhard , Zink Albert , Maixner Frank 
Published: February 2023

AbstractBackgroundIn 1975, the mummified body of a female has been found in the Franciscan church in Basel, Switzerland. Molecular and genealogic analyses unveiled her identity as Anna Catharina Bischoff (ACB), a member of the upper class of post-reformed Basel, who died at the age of 68 years, in 1787. The reason behind her death is still a mystery, especially that toxicological analyses revealed high levels of mercury, a common treatment against infections at that time, in different body organs. The computed tomography (CT) and histological analysis showed bone lesions in the femurs, the rib cage, and the skull, which refers to a potential syphilis case.ResultsAlthough we could not detect any molecular signs of the syphilis-causing pathogenTreponema pallidumsubsp. pallidum, we realized high prevalence of a nontuberculous mycobacterium (NTM) species in brain tissue sample. The genome analysis of this NTM displayed richness of virulence genes and toxins, and similarity to other infectious NTM, known to infect immunocompromised patients. In addition, it displayed potential resistance to mercury compounds, which might indicate a selective advantage against the applied treatment. This suggests that ACB might have suffered from an atypical mycobacteriosis during her life, which could explain the mummy’s bone lesion and high mercury concentrations.ConclusionsThe study of this mummy exemplifies the importance of employing differential diagnostic approaches in paleopathological analysis, by combining classical anthropological, radiological, histological, and toxicological observations with molecular analysis. It represents a proof-of-concept for the discovery of not-yet-described ancient pathogens in well-preserved specimens, using de novo metagenomic assembly.
Palmitoyl-glucosamine co-micronized with curcumin for maintenance of meloxicam-induced pain relief in dogs with osteoarthritis pain
Authors: della Rocca Giorgia , Schievano Carlo , Di Salvo Alessandra , Conti Maria Beatrice , della Valle Maria Federica 
Published: February 2023

Abstract
Background
Osteoarthritis (OA) pain is the number one cause of chronic pain in dogs. Multimodal treatment, including combining safe and effective nutritional interventions with non-steroidal anti-inflammatory drugs (NSAIDs), is currently considered one of the most appropriate choices for managing OA pain. Palmitoyl-glucosamine is a feed material belonging to the ALIAmide family, whose parent molecule is the prohomeostatic lipid amide N-palmitoyl-ethanolamine. Curcumin is a promising plant antioxidant. The present study aimed at investigating whether 18-week dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain pain relief in dogs with OA-associated chronic pain receiving meloxicam (1.5 mg/ml oral suspension) on a tapering regimen (progressive 25% decrease of the original 0.1 mg/kg/day dose, on a biweekly basis) during the first 8 weeks of treatment. Pain was assessed both by the owners and veterinary surgeons, with the first using both subjective evaluation and validated metrology instruments—i.e., Helsinki Chronic Pain Index (HCPI) and Canine Brief Pain Inventory (CBPI)—while the second rating the severity of lameness and pain on palpation on two previously used 5-point scales.

Results
A total of fifty-eight dogs with OA chronic pain entered the uncontrolled study. Pain on HCPI was considered severe at baseline (range 18–39). Based on owner’s assessment, 90% of dogs who responded to meloxicam at the full-dose regimen could reduce meloxicam up to 25% of the original dose without experiencing pain worsening. Moreover, 75% of dogs was assessed as having no pain increase ten weeks after meloxicam withdrawal. A statistically significant decrease of pain severity as scored by HCPI (P < 0.0001) was observed two and ten weeks after meloxicam withdrawal compared to study entry (17.0 ± 1.05 and 15.1 ± 1.02, respectively, vs 29.0 ± 0.74; mean ± SEM). After meloxicam withdrawal, no statistically significant change in the CBPI scores was recorded. Pain on palpation and lameness significantly changed to less severe distributions along the study period (P < 0.0001).

Conclusion
The findings appear to suggest that dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain meloxicam-induced pain relief in dogs with severe OA chronic pain.
CXCR3 predicts the prognosis of endometrial adenocarcinoma
Authors: Dong He , Sun Mengzi , Li Hua , Yue Ying 
Published: February 2023

Abstract
Objectives
Currently, endometrial adenocarcinoma lacks an effective prognostic indicator. This study was to develop and validate a gene biomarker and a nomogram to predict the survival of endometrial adenocarcinoma, explore potential mechanisms and select sensitive drugs.

Methods
425 endometrial adenocarcinoma cases with RNA sequencing data from TCGA were used to identify the most immune-related module by WGCNA. As an external test set, 103 cases from GSE17025 were used. Immune-related genes were downloaded from Innate DB. The three sets of data were used to identify the prognostic genes. Based on 397 cases with complete clinical data from TCGA, randomly divided into the training set (n = 199) and test set (n = 198), we identified CXCR3 as the prognostic gene biomarker. Age, grade, FIGO stage, and risk were used to develop and validate a predictive nomogram. AUC, C-index, calibration curve and K–M estimate evaluated the model's predictive performance. KEGG enrichment analysis, immune functions, TMB, the effectiveness of immunotherapy, and drug sensitivity between the high-risk and low-risk groups.

Results
CXCR3 was identified as a prognostic biomarker. We calculated the risk score and divided the cases into the high-risk and low-risk groups by the median value of the risk score. The OS of the high-risk group was better than the low-risk group. The risk was the prognostic indicator independent of age, grade, and FIGO stage. We constructed the nomogram including age, grade, FIGO stage, and risk to predict the prognosis of endometrial adenocarcinoma. The top five KEGG pathways enriched by the DEGs between the high- and low-risk groups were viral protein interaction with cytokine and cytokine receptors, cytokine-cytokine receptor interaction, chemokine signaling pathway, natural killer cell-mediated cytotoxicity, and cell adhesion molecules. We analyzed the difference in immune cells and found that CD8+ T cells, activated CD4+ T cells, T helper cells, monocytes, and M1 macrophages were infiltrated more in the low-risk group. However, M0 macrophages and activated dendritic cells were more in the high-risk group. The immune function including APC coinhibition, APC costimulation, CCR, checkpoint, cytolytic activity, HLA, inflammation-promoting, MHC-I, parainflammation, T cell coinhibition, T cell costimulation, type I-IFN-response, and type II-IFN-response were better in the low-risk group. TMB and TIDE scores were both better in the low-risk group. By ‘the pRRophetic’ package, we found 56 sensitive drugs for different risk groups.

Conclusion
We identified CXCR3 as the prognostic biomarker. We also developed and validated a predictive nomogram model combining CXCR3, age, histological grade, and FIGO stage for endometrial adenocarcinoma, which could help explore the precise treatment.
The chromatin-associated RNAs in gene regulation and cancer
Authors: Tang Jun , Wang Xiang , Xiao Desheng , Liu Shuang , Tao Yongguang 
Published: February 2023

AbstractEukaryotic genomes are prevalently transcribed into many types of RNAs that translate into proteins or execute gene regulatory functions. Many RNAs associate with chromatin directly or indirectly and are called chromatin-associated RNAs (caRNAs). To date, caRNAs have been found to be involved in gene and transcriptional regulation through multiple mechanisms and have important roles in different types of cancers. In this review, we first present different categories of caRNAs and the modes of interaction between caRNAs and chromatin. We then detail the mechanisms of chromatin-associated nascent RNAs, chromatin-associated noncoding RNAs and emerging m6A on caRNAs in transcription and gene regulation. Finally, we discuss the roles of caRNAs in cancer as well as epigenetic and epitranscriptomic mechanisms contributing to cancer, which could provide insights into the relationship between different caRNAs and cancer, as well as tumor treatment and intervention.
Longitudinal associations of movement behaviours with body composition and physical fitness from 4 to 9 years of age: structural equation and mediation analysis with compositional data
Authors: Migueles Jairo H. , Delisle Nyström Christine , Dumuid Dorothea , Leppänen Marja H. , Henriksson Pontus , Löf Marie 
Published: February 2023

Abstract
Background
The associations of movement behaviours (physical activity [PA], sedentary behaviour [SB], and sleep) with body composition and physical fitness from pre-school to childhood, as well as the direction of the associations, could provide important information for healthy lifestyle promotion in children. This study investigated the longitudinal and bidirectional associations of movement behaviours with body composition and physical fitness measured at 4 and 9 years of age.

Methods
This longitudinal study included baseline (n = 315, 4.5 [SD = 0.1] years) and follow-up data (n = 231, 9.6 [SD = 0.1] years) from the MINISTOP study. Movement behaviours were measured for 7 days using wrist-worn accelerometers, body composition with air-displacement plethysmography, and physical fitness with the ALPHA health-related fitness test battery. Cross-lagged panel models and mediation analyses were performed in combination with compositional data analysis.

Results
We did not observe direct associations of the movement behaviours at 4 years with either body composition or physical fitness at 9 years (all P > 0.05). However, fat mass index at 4 years was negatively associated with vigorous PA (VPA), relative to remaining behaviours (VPA, β = − 0.22, P = 0.002) and light PA (LPA), relative to SB and sleep (β = − 0.19, P = 0.016) at 9 years. VPA (relative to remaining), moderate PA (MPA) (relative to LPA, SB, and sleep), and SB (relative to sleep) tracked from 4 to 9 years (all β ≥ 0.17, all P < 0.002), and these behaviours shared variance with fat mass index (all|β| ≥ 0.19, all P < 0.019), and aerobic, motor, and muscular fitness (all|β| ≥ 0.19, all P < 0.014) at 9 years. Mediation analysis suggested that the tracking of VPA (relative to remaining behaviours) from 4 to 9 years was negatively associated with fat mass index (β ≥ − 0.45, P = 0.012), and positively with aerobic fitness at 9 years (β ≥ 1.64, P = 0.016).

Conclusion
PA and SB tracked from the pre-school years into childhood. Fat mass index at 4 years of age was negatively associated with VPA (relative to remaining behaviours) and LPA (relative to SB and sleep) at 9 years of age. The tracking of VPA was associated with lower fat mass index and higher aerobic fitness at 9 years of age. These findings suggest that higher levels of VPA in pre-school age, if maintained throughout childhood, may support the development of healthy body composition and aerobic fitness levels in later childhood.
Shorter sleep among adolescents is associated with lower fruit and vegetable consumption the following day
Authors: Winpenny Eleanor M. , Rowthorn Harriet , Hollidge Stefanie , Westgate Kate , Goodyer Ian M. , Brage Soren , van Sluijs Esther M. F. 
Published: February 2023

Abstract

Background
Insufficient sleep has been associated with weight gain and metabolic dysregulation, with one suggested mechanism being through reduction in diet quality. Experimental evidence supports a causal effect of sleep timings on diet but this may not be applicable to a free-living adolescent population. In this analysis we use daily measures of sleep timings and diet quality, to examine the effect of sleep duration and timing on diet quality the following day among free-living adolescents.

Methods
The ROOTS study is a prospective cohort recruited from secondary schools in Cambridgeshire and Suffolk (UK). Participants (n = 815) at mean age 15.0y (SD 0.3y) completed a diet diary and wore a combined heart rate and accelerometer device over 4 consecutive days. Sleep duration and timing (midpoint) were derived from acceleration and heart rate traces, while daily energy density and fruit and vegetable intake were calculated from dietary data. Analyses were performed at day-level (1815 person-days). Multilevel random effects models were used to test associations between sleep each night and subsequent day diet, with daily sleep and diet measures nested within individuals and schools, and adjusted for day-level and individual-level confounding variables.

Results
Adolescents slept a mean of 7.88 hrs (SD 1.10) per night, reporting a mean energy density of 2.12 kcal/g (SD 0.48) and median energy-adjusted daily fruit and vegetable intake of 137.3 g (IQR 130.4). One hour shorter sleep duration was associated with lower intake of fruit and vegetables (-6.42 g, 95%CI -1.84, -10.99) the following day. An association with higher dietary energy density (0.016 kcal/g, 95%CI 0.034, -0.002) the following day was observed but did not reach statistical significance. Sleep timing was not associated with either fruit and vegetable intake (-2.52 g/d, 95%CI -7.66, 2.62) or dietary energy density (-0.001 kcal/g, 95%CI -0.022, 0.020).

Conclusions
Our observational findings from a free-living adolescent population support the experimental evidence for a causal role of sleep on diet, with shorter sleep duration at night leading to a small decrease in diet quality the following day. These findings support experimental evidence to suggest inclusion of sleep duration as one component of interventions designed to improve diet quality and weight status in adolescents.
Association between sleep duration and metabolic syndrome: linear and nonlinear Mendelian randomization analyses
Authors: Liang Yannis Yan , Chen Jie , Peng Miaoguan , Zhou Jiajin , Chen Xinru , Tan Xiao , Wang Ningjian , Ma Huan , Guo Lan , Zhang Jihui , Wing Yun-Kwok , Geng Qingshan , Ai Sizhi 
Published: February 2023

Abstract
Background
Observational studies have found that both short and long sleep duration are associated with increased risk of metabolic syndrome (MetS). This study aimed to examine the associations of genetically determined sleep durations with MetS and its five components (i.e., central obesity, high blood pressure, dyslipidemia, hypertriglyceridemia, and hyperglycemia) among a group of elderly population.

Methods
In 335,727 participants of White British from the UK Biobank, linear Mendelian randomization (MR) methods were first employed to examine the causal association of genetically predicted continuous sleep duration with MetS and its each component. Nonlinear MR analyses were performed to determine the nonlinearity of these associations. The causal associations of short and long sleep duration with MetS and its components were further assessed by using genetic variants that associated with short (≤ 6 h) and long sleep (≥ 9 h) durations.

Results
Linear MR analyses demonstrated that genetically predicted 1-h longer sleep duration was associated with a 13% lower risk of MetS, a 30% lower risk of central obesity, and a 26% lower risk of hyperglycemia. Non-linear MR analyses provided evidence for non-linear associations of genetically predicted sleep duration with MetS and its five components (all P values < 0.008). Genetically predicted short sleep duration was moderately associated with MetS and its four components, including central obesity, dyslipidemia, hypertriglyceridemia, and hyperglycemia (all P values < 0.002), whereas genetically long sleep duration was not associated with MetS and any of its components.

Conclusions
Genetically predicted short sleep duration, but not genetically predicted long sleep duration, is a potentially causal risk factor for MetS.

Graphical Abstract
Robust SNP-based prediction of rheumatoid arthritis through machine-learning-optimized polygenic risk score
Authors: Lim Ashley J. W. , Tyniana C. Tera , Lim Lee Jin , Tan Justina Wei Lynn , Koh Ee Tzun ,   TTSH Rheumatoid Arthritis Study Group, Ang Andrea Ee Ling , Chan Grace Yin Lai , Chan Madelynn Tsu-Li , Chia Faith Li-Ann , Chng Hiok Hee , Chua Choon Guan , Howe Hwee Siew , Koh Li Wearn , Kong Kok Ooi , Law Weng Giap , Lee Samuel Shang Ming , Lian Tsui Yee , Lim Xin Rong , Loh Jess Mung Ee , Manghani Mona , Tan Sze-Chin , Teo Claire Min-Li , Thong Bernard Yu-Hor , Tjokrosaputro Paula Permatasari , Xu Chuanhui , Chong Samuel S. , Khor Chiea Chuen , Leong Khai Pang , Lee Caroline G. 
Published: February 2023

Abstract
Background
The popular statistics-based Genome-wide association studies (GWAS) have provided deep insights into the field of complex disorder genetics. However, its clinical applicability to predict disease/trait outcomes remains unclear as statistical models are not designed to make predictions. This study employs statistics-free machine-learning (ML)-optimized polygenic risk score (PRS) to complement existing GWAS and bring the prediction of disease/trait outcomes closer to clinical application. Rheumatoid Arthritis (RA) was selected as a model disease to demonstrate the robustness of ML in disease prediction as RA is a prevalent chronic inflammatory joint disease with high mortality rates, affecting adults at the economic prime. Early identification of at-risk individuals may facilitate measures to mitigate the effects of the disease.

Methods
This study employs a robust ML feature selection algorithm to identify single nucleotide polymorphisms (SNPs) that can predict RA from a set of training data comprising RA patients and population control samples. Thereafter, selected SNPs were evaluated for their predictive performances across 3 independent, unseen test datasets. The selected SNPs were subsequently used to generate PRS which was also evaluated for its predictive capacity as a sole feature.

Results
Through robust ML feature selection, 9 SNPs were found to be the minimum number of features for excellent predictive performance (AUC > 0.9) in 3 independent, unseen test datasets. PRS based on these 9 SNPs was significantly associated with (P < 1 × 10–16) and predictive (AUC > 0.9) of RA in the 3 unseen datasets. A RA ML-PRS calculator of these 9 SNPs was developed (https://xistance.shinyapps.io/prs-ra/) to facilitate individualized clinical applicability. The majority of the predictive SNPs are protective, reside in non-coding regions, and are either predicted to be potentially functional SNPs (pfSNPs) or in high linkage disequilibrium (r2 > 0.8) with un-interrogated pfSNPs.

Conclusions
These findings highlight the promise of this ML strategy to identify useful genetic features that can robustly predict disease and amenable to translation for clinical application.
Multi-omics data reveals the important role of glycerophospholipid metabolism in the crosstalk between gut and brain in depression
Authors: Xie Jing , Zhong Qi , Wu Wen-tao , Chen Jian-jun 
Published: February 2023

Abstract
Background
Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to observe the characteristics of gut microbiota, lipid metabolism and neurotransmitters in Gut-Liver-Brain axis in depressed mice (DM), and identify some novel perceptions on relationships between gut microbiota and depression.

Methods
A mouse model of depression was built used chronic unpredictable mild stress (CUMS). Fecal samples (measuring gut microbiota compositions, microbial genes and lipid metabolites), liver samples (measuring lipid metabolites), and hippocampus (measuring neurotransmitters) were collected. Both univariate and multivariate statistical analyses were used to identify the differential gut microbiota, metabolic signatures and neurotransmitters in DM.

Results
There were significant differences on both microbial and metabolic signatures between DM and control mice (CM): 71 significantly changed operational taxonomic units (OTUs) (60.56% belonged to phylum Firmicutes) and 405 differential lipid metabolites (51.11% belonged to Glycerophospholipid (GP) metabolism) were identified. Functional analysis showed that depressive-like behaviors (DLB)-related differential microbial genes were mainly enriched in GP metabolism. Weighted correlation network analysis (WGCNA) showed that DLB-related differential metabolites mainly belonged to GPs. Meanwhile, seven differential neurotransmitters were identified. Comprehensive analysis found that Lachnospiraceae and gamma-aminobutyric acid (GABA) were significantly correlated with 94.20% and 53.14% differential GPs, respectively, and GABA was significantly correlated with three main DLB phenotypes.

Conclusion
Our results provided novel perceptions on the role of Gut-Liver-Brain axis in the onset of depression, and showed that GP metabolism might be the bridge between gut microbiota and depression. “Lachnospiraceae-GP metabolism-GABA” held the promise as a potential way between gut microbiota and brain functions in DM.
Stratum corneum hydration inversely correlates with certain serum cytokine levels in the elderly, possibly contributing to inflammaging
Authors: Yang Bin , Lv Chengzhi , Ye Li , Wang Zhen , Kim Yoon , Luo Wenhai , Elias Peter M. , Man Mao-Qiang 
Published: February 2023

Abstract
Background
Chronic, low-grade inflammation, also termed ‘inflammaging’, has been linked to the development of some aging-associated disorders. Recent studies suggest that inflammaging is attributable to aging-associated epidermal dysfunction. However, abnormality in which epidermal function contributes to inflammaging is not clear.

Objective
We delineated the correlation of epidermal functions with circulating levels of proinflammatory cytokines in the elderly.

Methods
Blood sample was collected from a total of 255 participants aged ≥ 65 years. Epidermal biophysical properties were measured on the left forearm and the right shin. Serum cytokine levels were measured by Multiplex Luminex Assays.

Results
Neither skin surface pH nor transepidermal water loss rates (TEWL) correlated with serum cytokine levels except TEWL on the right shin for TNFa (p < 0.05). In contrast, stratum corneum hydration levels on both the forearm and the shin correlated negatively with serum cytokine levels (p < 0.05).

Conclusion
Reduced stratum corneum hydration likely contributes to inflammaging.