bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allelic diversity of the pharmacogene CYP2D6 in New Zealand Māori and Pacific peoples
Authors: Hitchman Leonie M. , Faatoese Allamanda , Merriman Tony R. , Miller Allison L. , Liau Yusmiati , Graham Oscar E. E. , Kee Ping Siu , Pearson John F. , Fakahau Tony , Cameron Vicky A. , Kennedy Martin A. , Maggo Simran D. S. 
Published: October 2022

The enzyme cytochrome P450 2D6 (CYP2D6) metabolises approximately 25% of commonly prescribed drugs, including analgesics, anti-hypertensives, and anti-depressants, among many others. Genetic variation in drug metabolising genes can alter how an individual responds to prescribed drugs, including predisposing to adverse drug reactions. The majority of research on the CYP2D6 gene has been carried out in European and East Asian populations, with many Indigenous and minority populations, such as those from Oceania, greatly underrepresented. However, genetic variation is often population specific and analysis of diverse ethnic groups can reveal differences in alleles that may be of clinical significance. For this reason, we set out to examine the range and frequency of CYP2D6 variants in a sample of 202 Māori and Pacific people living in Aotearoa (New Zealand). We carried out long PCR to isolate the CYP2D6 region before performing nanopore sequencing to identify all variants and alleles in these samples. We identified twelve variants which have previously not been reported in the PharmVar CYP2D6 database, three of which were exonic missense variations. Six of these occurred in single samples and one was found in 19 samples (9.4% of the cohort). The remaining five variants were identified in two samples each. Identified variants formed twelve new CYP2D6 suballeles and four new star alleles, now recorded in the PharmVar database. One striking finding was that CYP2D6*71, an allele of uncertain functional status which has been rarely observed in previous studies, occurs at a relatively high frequency (8.9%) within this cohort. These data will help to ensure that CYP2D6 genetic analysis for pharmacogenetic purposes can be carried out accurately and effectively in this population group.
Identification of senescence-associated long non-coding RNAs to predict prognosis and immune microenvironment in patients with hepatocellular carcinoma
Authors: Gao Chengzhi , Zhou Guangming , Cheng Min , Feng Lan , Cao Pengbo , Zhou Gangqiao 
Published: October 2022

Background: Cellular senescence plays a complicated and vital role in cancer development because of its divergent effects on tumorigenicity. However, the long non-coding RNAs (lncRNAs) associated with tumor senescence and their prognostic value in hepatocellular carcinoma (HCC) remain unexplored.Methods: The trans-cancer oncogene-induced senescence (OIS) signature was determined by gene set variation analysis (GSVA) in the cancer genome atlas (TCGA) dataset. The OIS-related lncRNAs were identified by correlation analyses. Cox regression analyses were used to screen lncRNAs associated with prognosis, and an optimal predictive model was created by regression analysis of the least absolute shrinkage and selection operator (LASSO). The performance of the model was evaluated by Kaplan-Meier survival analyses, nomograms, stratified survival analyses, and receiver operating characteristic curve (ROC) analyses. Gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) were carried out to explore the functional relevance and immune cell infiltration, respectively.Results: Firstly, we examined the pan-cancer OIS signature, and found several types of cancer with OIS strongly associated with the survival of patients, including HCC. Subsequently, based on the OIS signature, we identified 76 OIS-related lncRNAs with prognostic values in HCC. We then established an optimal prognostic model based on 11 (including NRAV, AC015908.3, MIR100HG, AL365203.2, AC009005.1, SNHG3, LINC01138, AC090192.2, AC008622.2, AL139423.1, and AC026356.1) of these lncRNAs by LASSO-Cox regression analysis. It was then confirmed that the risk score was an independent and potential risk indicator for overall survival (OS) (HR [95% CI] = 4.90 [2.74–8.70], p &lt; 0.001), which outperforms those traditional clinicopathological factors. Furthermore, patients with higher risk scores also showed more advanced levels of a proinflammatory senescence-associated secretory phenotype (SASP), higher infiltration of regulatory T (Treg) cells and lower infiltration of naïve B cells, suggesting the regulatory effects of OIS on immune microenvironment. Additionally, we identified NRAV as a representative OIS-related lncRNA, which is over-expressed in HCC tumors mainly driven by DNA hypomethylation.Conclusion: Based on 11 OIS-related lncRNAs, we established a promising prognostic predictor for HCC patients, and highlighted the potential immune microenvironment-modulatory roles of OIS in HCC, providing a broad molecular perspective of tumor senescence.
Sex-specific association between alcohol consumption and liver cirrhosis: An updated systematic review and meta-analysis
Authors: Llamosas-Falcón Laura , Probst Charlotte , Buckley Charlotte , Jiang Huan , Lasserre Aurélie M. , Puka Klajdi , Tran Alexander , Rehm Jürgen 
Published: October 2022

Different studies have shown that females develop liver diseases at lower levels of alcohol consumption than males. Our aim was to quantify the dose-response relationship between alcohol consumption and the risk of liver cirrhosis by sex and identify the differences between females and males. A systematic review was conducted using PubMed/Medline and Embase to identify longitudinal and case-control studies that analyzed the relationship between the level of alcohol use and liver cirrhosis (LC) incidence, and mortality (ICD-8 and ICD-9 codes 571 and ICD-10 codes K70, K73, K74). Pooled relative risks (RR) were calculated by random effects models. Restricted cubic splines were used to model the dose-response relationship. A total of 24 studies were included in the analysis. There were collectively 2,112,476 females and 924,853 males, and a total of 4,301 and 4,231 cases of LC for females and males, respectively. We identified a non-linear dose-response relationship. Females showed a higher risk for LC compared to males with the same amount of alcohol consumed daily. For instance, drinking 40 g/day showed RRs of 9.35 (95% CI 7.64-11.45) in females and 2.82 (95% CI 2.53-3.14) in males, while drinking 80 g/day presented RRs of 23.32 (95% CI 18.24-29.82) in females and 7.93 (95% CI 7.12-8.83) in males. Additional analyses showed that a higher risk for females was found for morbidity and for mortality. Understanding the influence of sex on the association of alcohol consumption and the risk of LC is needed to develop recommendations and clinical guidelines for prevention and treatment.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022299680, identifier CRD42022299680.
Effect of calorie-restriction and rapamycin on autophagy and the severity of caerulein-induced experimental acute pancreatitis in mice
Authors: Sharma Manish Kumar , Priyam Kumari , Kumar Punit , Garg Pramod Kumar , Roy Tara Sankar , Jacob Tony George 
Published: October 2022

BackgroundImpaired autophagy contributes to development of acute pancreatitis (AP). We studied the effect of inducing autophagy by calorie-restriction and rapamycin, separately, in the caerulein-induced model of severe AP.MethodsAdult, male, Swiss albino mice were given eight, hourly, intraperitoneal injections of caerulein (Ce) (50µg/Kg/dose). The interventions were calorie restriction (CR) and rapamycin (2mg/Kg). Mice were sacrificed at the 9th hour. Pancreas was harvested for histopathology and immunoblotting. Amylase activity and the levels of cytokines were measured in plasma.ResultsThe histopathological score and amylase activity were significantly lower in calorie-restricted caerulein-induced AP (CRCeAP) in comparison to animals that had unrestricted access to chow. In the CRCeAP group, levels of IL-6 and GM-CSF in plasma were lower and the expression of LC3II and Beclin-1 were higher. On transmission electron-microscopy, the area occupied by autophagic vacuoles was higher in CRCeAP. The expression of caspase-8 and caspase-9 was also higher in CRCeAP. In rapamycin with caerulein-induced AP (Rapa+CeAP), the histopathological score and amylase activity were significantly lower than caerulein-induced AP (CeAP). In Rapa+CeAP, the expression of LC3II and Beclin-1 were higher, whereas; SQSTM1 was decreased. The number of autophagic vacuoles in Rapa+CeAP group was fewer. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were lower in Rapa+CeAP. Caspase-3 increased and high mobility group box 1 (HMGB1) decreased in Rapa+CeAP.ConclusionCalorie-restriction and rapamycin can individually decrease the severity of injury in the caerulein-induced model of severe AP.
Prognostic analysis and validation of diagnostic marker genes in patients with osteoporosis
Authors: Wang Xing , Pei Zhiwei , Hao Ting , Ariben Jirigala , Li Siqin , He Wanxiong , Kong Xiangyu , Chang Jiale , Zhao Zhenqun , Zhang Baoxin 
Published: October 2022

BackgroundsAs a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass and bone microarchitectural damage. The global incidences of OP are high.MethodsData were retrieved from databases like Gene Expression Omnibus (GEO), GeneCards, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Gene Expression Profiling Interactive Analysis (GEPIA2), and other databases. R software (version 4.1.1) was used to identify differentially expressed genes (DEGs) and perform functional analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and random forest algorithm were combined and used for screening diagnostic markers for OP. The diagnostic value was assessed by the receiver operating characteristic (ROC) curve. Molecular signature subtypes were identified using a consensus clustering approach, and prognostic analysis was performed. The level of immune cell infiltration was assessed by the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. The hub gene was identified using the CytoHubba algorithm. Real-time fluorescence quantitative PCR (RT-qPCR) was performed on the plasma of osteoporosis patients and control samples. The interaction network was constructed between the hub genes and miRNAs, transcription factors, RNA binding proteins, and drugs.ResultsA total of 40 DEGs, eight OP-related differential genes, six OP diagnostic marker genes, four OP key diagnostic marker genes, and ten hub genes (TNF, RARRES2, FLNA, STXBP2, EGR2, MAP4K2, NFKBIA, JUNB, SPI1, CTSD) were identified. RT-qPCR results revealed a total of eight genes had significant differential expression between osteoporosis patients and control samples. Enrichment analysis showed these genes were mainly related to MAPK signaling pathways, TNF signaling pathway, apoptosis, and Salmonella infection. RT-qPCR also revealed that the MAPK signaling pathway (p38, TRAF6) and NF-kappa B signaling pathway (c-FLIP, MIP1β) were significantly different between osteoporosis patients and control samples. The analysis of immune cell infiltration revealed that monocytes, activated CD4 memory T cells, and memory and naïve B cells may be related to the occurrence and development of OP.ConclusionsWe identified six novel OP diagnostic marker genes and ten OP-hub genes. These genes can be used to improve the prognostic of OP and to identify potential relationships between the immune microenvironment and OP. Our research will provide insights into the potential therapeutic targets and pathogenesis of osteoporosis.
Stereoscopic vs. monoscopic photographs on optic disc evaluation and glaucoma diagnosis among general ophthalmologists: A cloud-based real-world multicenter study
Authors: Yang Jingyuan , Qu Yi , Zhao Jianchun , Cong Jingwu , Sun Zixi , Du Yunfeng , Yang Gang , Ding Dayong , Chen Youxin , Cheng Gangwei 
Published: October 2022

PurposeTo investigate whether stereoscopic vs. monoscopic viewing condition influences the evaluation of optic disc photographs for morphologic features and glaucoma likelihood in a general ophthalmologist population from multicenters on a cloud-based platform.MethodsA cross-sectional study of 519 pairs of stereoscopic and monoscopic photographs of optic discs with adequate quality were selected and presented using a cloud-based platform. A total of 21 general ophthalmologists from 14 centers assessed 15 morphologic features based on 5R's rules and estimated glaucoma likelihood for each assigned photograph. There were 93 pairs of stereoscopic and monoscopic photographs evaluated by a panel of glaucoma specialists and set as ground truth. The main outcome measures were the agreement between estimates and ground truth and the inter-grader agreements.ResultsThere were good agreements between ground truth and both monoscopic and stereoscopic estimates (stereo κ 0.532 and mono κ 0.494). There was also a substantial intra-grader agreement between monoscopic and stereoscopic evaluation of glaucoma likelihood (κ 0.636). In eyes with probable glaucoma, the accuracy of the stereo method was greater than that of the mono method (stereo 0.238 vs. mono 0.118) When compared with ground truth, stereoscopic photographs had a better agreement for disc size (stereo κ 0.447 vs. mono κ 0.183), disc color (stereo κ 0.612 vs. mono κ 0.549), neuroretinal rim shape (stereo κ 0.356 vs. mono κ 0.274) on the whole. The stereoscopic method also had a better inter-grade agreement for disc size, disc color, neuroretinal rim shape, and glaucoma likelihood (stereo κ 0.402 vs. mono κ 0.359) on the whole.ConclusionsIn the evaluation of optic disc photographs for morphologic features and glaucoma likelihood, the stereoscopic method showed superiority compared to the monoscopic method for general ophthalmologists. The stereoscopic method is more likely to identify glaucomatous eyes which need medical intervention.
Monocytohigh-density lipoprotein ratio has a high predictive value for the diagnosis of multiple system atrophy and the differentiation from Parkinson’s disease
Authors: Jiang Lijuan , Zhong Zhen , Huang Juan , Bian Hetao , Huang Wei 
Published: October 2022

Background and purposeInflammation is closely related to the pathogenesis of multiple system atrophy (MSA). As markers of inflammation, the monocyte to high-density lipoprotein ratio (MHR), neutrophil to lymphocyte ratio (NLR), and red cell distribution width to platelet ratio (RPR) have been proven to be associated with a large variety of diseases. The aim of this study was to explore the association between inflammatory markers (MHR, NLR, and RPR) and MSA, and the difference between MSA and Parkinson’s disease (PD) was further compared by these inflammatory markers.Materials and methodsThis study was divided into three groups: 47 patients with MSA, 125 patients with PD, and 124 healthy controls. The corresponding laboratory indicators of subjects were collected and analyzed to obtain MHR, NLR, and RPR values.ResultsCompared with healthy controls, the MHR, NLR, and RPR were higher in the MSA group (P &lt; 0.05), and the MHR was higher in the MSA group than in the PD group (P &lt; 0.001). Multivariate logistic regression analysis showed that MHR*10 (corrected OR = 1.312, 95% CI 1.093–1.575) and RPR*100 (corrected OR = 1.262, 95% CI 1.055–1.509) were positively correlated with the risk of MSA. The receiver operating characteristic (ROC) curve indicated that the areas under the curve (AUCs) of the MHR, NLR, and RPR for predicting MSA were 0.651 (95% CI 0.562–0.74; P &lt; 0.05), 0.6 (95% CI 0.501–0.699; P &lt; 0.05), and 0.612 (95% CI 0.516–0.708; P &lt; 0.05), respectively. The AUC of MSA and PD predicted by the MHR was 0.727 (P &lt; 0.001). When the cut-off value was 0.38, the sensitivity and specificity were 60 and 77%, respectively. Spearman correlation analysis showed that the MHR was significantly and positively correlated with the course of MSA cerebellar type (MSA-C) patients.ConclusionThere may be peripheral inflammation in patients with MSA. Compared with NLR and RPR, MHR has higher predictive value for the diagnosis and differential diagnosis of MSA.
Dose-staged Gamma Knife radiosurgery for meningiomas: A retrospective study in a single center
Authors: Gong Xiu , Ding Jianbo , Knisely Jonathan P. S. , Wang Enmin , Pan Li , Wang Binjiang , Zhang Nan , Wu Hanfeng , Dai Jiazhong , Yu Tonggang , Tang Xuqun 
Published: October 2022

ObjectiveThis study aimed to study the efficiency and safety of a dose-staged Gamma Knife radiosurgery strategy for large meningiomas or meningiomas close to important nerve structures.MethodsThis study evaluates the outcome of a prospectively accrued series of 71 consecutive patients with meningiomas treated with staged dose-fractionated Gamma Knife radiosurgery. The average peripheral doses for the first and second fractions were 9.0 ± 0.9 Gy (8–12 Gy) and 8.6 ± 0.7 Gy (range, 7–10 Gy), respectively. The interval between fractions was 6.1 ± 1.9 months (range, 3–12 months). The median follow-up time was 36 months (12–96 months).ResultsDuring the follow-up period after the second fraction, 97.2% achieved tumor control in our series. A total of 2 patients exhibited local recurrence at 30 and 60 months after the second fraction, respectively. No treatment-related complications or new long-term neurological dysfunctions were reported. MRIs observed slightly or moderately increased peritumoral edema in six patients, but no specific neurological complaints are attributed to this finding.ConclusionThis study investigates the efficiency and safety of dose-staged Gamma Knife radiosurgery as an alternative option for meningiomas that were large in volume, adjacent to crucial structures, or in patients with contraindications to craniotomy.
Surgical quadriceps lengthening can reduce quadriceps spasticity in chronic stroke patients. A case-control study
Authors: Merlo Andrea , Galletti Martina , Zerbinati Paolo , Prati Paolo , Mascioli Francesca , Basini Giacomo , Rambelli Chiara , Masiero Stefano , Mazzoli Davide 
Published: October 2022

BackgroundMuscle overactivity is one of the positive signs of upper motor neuron lesions. In these patients, the loss of muscle length and extensibility resulting from soft tissue rearrangement has been suggested as a contributing cause of muscle overactivity in response to stretching.ObjectiveTo assess the effects of surgical lengthening of the quadriceps femoris (QF) muscle-tendon unit by aponeurectomy on muscle spasticity.MethodsThis is a case-control study on chronic stroke patients with hemiparesis that have undergone lower limb functional surgery over a 8-year period. CASEs underwent corrective surgery for both the foot and knee deviations, inclusive of a QF aponeurectomy. Controls (CTRLs) underwent corrective surgery for foot deviations only. QF spasticity was assessed with the Modified Tardieu Scale (MTS) before and 1 month after surgery. The Wilcoxon test was used to assess MTS variations over time and the Mann–Whitney test was used to verify the presence of group differences at the 1 month mark.ResultsNinety-three patients were included: 57 cases (30F, 1–34 years from lesion) and 36 controls (12F, 1–35 years from lesion). Before surgery, both CASEs and CTRLs had similar MTS scores (median MTS = 3) and functional characteristics. One month after surgery, QF spasticity was significantly lower in the CASEs compared to CTRLs (p = 0.033) due to a significant reduction of the median MTS score from 3 to 0 in the CASE group (p &lt; 0.001) and no variations in the CTRL group (p = 0.468). About half of the cases attained clinically significant MTS reductions and complete symptom relief even many years from the stroke.ConclusionsFunctional surgery inclusive of QF aponeurectomy can be effective in reducing or suppressing spasticity in chronic stroke patients. This is possibly a result of the reduction in neuromuscular spindle activation due to a decrease in muscle shortening, passive tension, and stiffness.
Early nutritional intake influences the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor in preterm newborns
Authors: De Nardo Maria Chiara , Petrella Carla , Di Chiara Maria , Di Mario Chiara , Deli Giorgia , Travaglia Elisa , Baldini Laura , Russo Alessia , Parisi Pasquale , Fiore Marco , Terrin Gianluca 
Published: October 2022

IntroductionParenteral nutrition (PN) may have detrimental effects on neurodevelopment in preterm newborns. Moreover, enteral nutrition (EN) seems to be protective. To understand the mechanisms of how neurological development can be influenced by the route of administration of nutritional intake, we investigated the relationship between the serum levels of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and nutritional intake received in early life by preterm newborns.Materials and methodsSpecimens of blood were obtained at 28 days of life (DOL) for NGF/BDNF determination in neonates &lt;32 weeks of gestation and/or with birth weight &lt;1,500 g, consecutively observed in the neonatal intensive care unit. We analyzed the relation between amino acid content and energy intake and NGF/BDNF measurements at 28 DOL. PN protein intake was referred to as the total amounts of amino acid intake received daily.ResultsWe enrolled 20 newborns (gestational age 30.45 ± 1.76 weeks, birth weight 1,340 ± 352.63 g). Serum NGF value at 28 DOL was positively correlated with enteral protein and energy intake (r = 0.767; r = 0.746, p &lt; 0.001), whereas, negatively correlated with parenteral amino acid and energy intake (r = −0.652, p &lt; 0.001; r = −0.466, p &lt; 0.05). Similar significant correlations were described between BDNF level at 28 DOL and enteral energy intake (r = 0.493, p &lt; 0.05). Multivariate regression analysis showed that NGF level at 28 DOL depends on enteral protein and energy intake administrated in the 1st week of life.ConclusionNeurotrophin values varied according to the route of nutrition administration in preterm newborns. NGF/BDNF serum levels are influenced positively and negatively by EN and PN, respectively.
Comparisons of tri-ponderal mass index and body mass index in discriminating hypertension at three separate visits in adolescents: A retrospective cohort study
Authors: Hu Jia , Zhong Yi , Ge WenXin , Lv Huiling , Ding Ziyao , Han Di , Hai Bo , Shen Hui , Yin Jieyun , Gu Aihua , Yang Haibing 
Published: October 2022

ObjectiveTo estimate whether the new obesity indicator tri-ponderal mass index (TMI) has a better capacity to predict adolescent hypertension (HTN) and HTN subtypes at three separate blood pressure (BP) visits than the conventionally used body mass index (BMI).MethodsA total of 36,950 adolescents who had initial normal BP from 2012 to 2019 were included in Suzhou, China. HTN was defined as having three separate visits of elevated BP in 2020. The area under the receiver-operating characteristic curve (AUC), false-positive rate, false-negative rate, total misclassification rates, net reclassification improvement (NRI), and integrated discrimination improvement were calculated to compare the discriminative ability of HTN between BMI and TMI.ResultsTMI had better predictive abilities than BMI among all of the participants when predicting HTN (difference in AUC = 0.019, 95% CI = 0.007–0.031; NRI = 0.067, 95% CI = 0.008–0.127) and isolated systolic hypertension (difference in AUC = 0.021, 95% CI = 0.005–0.036; NRI = 0.106, 95% CI = 0.029–0.183). The difference in prediction abilities between BMI and TMI was more obvious in the subgroup of age ≥16. Also, TMI outperformed BMI in predicting adolescent HTN in girls but not in boys.ConclusionCompared with BMI, TMI may have a better predictive capacity for HTN, particularly in girls and older adolescents. TMI has the potential to be used as an effective predictor for HTN in clinic practice. Further studies are needed to verify the utility of TMI.