bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 infection dysregulates NAD metabolism
Authors: Izadpanah Amin , Mudd Joseph C. , Garcia Joe G. N. , Srivastav Sudesh , Abdel-Mohsen Mohamed , Palmer Clovis , Goldman Aaron R. , Kolls Jay K. , Qin Xuebin , Rappaport Jay 
Published: June 2023

IntroductionSevere COVID-19 results initially in pulmonary infection and inflammation. Symptoms can persist beyond the period of acute infection, and patients with Post-Acute Sequelae of COVID (PASC) often exhibit a variety of symptoms weeks or months following acute phase resolution including continued pulmonary dysfunction, fatigue, and neurocognitive abnormalities. We hypothesized that dysregulated NAD metabolism contributes to these abnormalities.MethodsRNAsequencing of lungs from transgenic mice expressing human ACE2 (K18-hACE2) challenged with SARS-CoV-2 revealed upregulation of NAD biosynthetic enzymes, including NAPRT1, NMNAT1, NAMPT, and IDO1 6 days post-infection.ResultsOur data also demonstrate increased gene expression of NAD consuming enzymes: PARP 9,10,14 and CD38. At the same time, SIRT1, a protein deacetylase (requiring NAD as a cofactor and involved in control of inflammation) is downregulated. We confirmed our findings by mining sequencing data from lungs of patients that died from SARS-CoV-2 infection. Our validated findings demonstrating increased NAD turnover in SARS-CoV-2 infection suggested that modulating NAD pathways may alter disease progression and may offer therapeutic benefits. Specifically, we hypothesized that treating K18-hACE2 mice with nicotinamide riboside (NR), a potent NAD precursor, may mitigate lethality and improve recovery from SARS-CoV-2 infection. We also tested the therapeutic potential of an anti- monomeric NAMPT antibody using the same infection model. Treatment with high dose anti-NAMPT antibody resulted in significantly decreased body weight compared to control, which was mitigated by combining HD anti-NAMPT antibody with NR. We observed a significant increase in lipid metabolites, including eicosadienoic acid, oleic acid, and palmitoyl carnitine in the low dose antibody + NR group. We also observed significantly increased nicotinamide related metabolites in NR treated animals.DiscussionOur data suggest that infection perturbs NAD pathways, identify novel mechanisms that may explain some pathophysiology of CoVID-19 and suggest novel strategies for both treatment and prevention.
Prognostic models for predicting postoperative recurrence in Crohn’s disease: a systematic review and critical appraisal
Authors: Chen Rirong , Zheng Jieqi , Li Chao , Chen Qia , Zeng Zhirong , Li Li , Chen Minhu , Zhang Shenghong 
Published: June 2023

Background and AimsProphylaxis of postoperative recurrence is an intractable problem for clinicians and patients with Crohn’s disease. Prognostic models are effective tools for patient stratification and personalised management. This systematic review aimed to provide an overview and critically appraise the existing models for predicting postoperative recurrence of Crohn’s disease.MethodsSystematic retrieval was performed using PubMed and Web of Science in January 2022. Original articles on prognostic models for predicting postoperative recurrence of Crohn’s disease were included in the analysis. The risk of bias was assessed using the Prediction Model Risk of Bias Assessment (PROBAST) tool. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO; number CRD42022311737).ResultsIn total, 1948 articles were screened, of which 15 were ultimately considered. Twelve studies developed 15 new prognostic models for Crohn’s disease and the other three validated the performance of three existing models. Seven models utilised regression algorithms, six utilised scoring indices, and five utilised machine learning. The area under the receiver operating characteristic curve of the models ranged from 0.51 to 0.97. Six models showed good discrimination, with an area under the receiver operating characteristic curve of &gt;0.80. All models were determined to have a high risk of bias in modelling or analysis, while they were at low risk of applicability concerns.ConclusionsPrognostic models have great potential for facilitating the assessment of postoperative recurrence risk in patients with Crohn’s disease. Existing prognostic models require further validation regarding their reliability and applicability.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022311737.
The first mass drug administration campaign for schistosomiasis control in Lagos, Nigeria: lessons for future control programs
Authors: Olamiju Francisca O. , Nebe Obiageli , Mogaji Hammed , Abdus-Salam Ismail , Jenrola Lanre , Marcus Ayodele J. , Olamiju Olatunwa J. , Isiyaku Sunday , Amodu-Agbi Perpetua , Nwoye Ikenna , Achu Ijeoma , Abah Emmanuel 
Published: June 2023

BackgroundIn this study we summarized the lessons learnt during the first effective mass drug administration (MDA) campaign in one of the most urbanized states in Nigeria. We particularly discuss the implementation approach including associated challenges and future prospects.MethodsWe implemented schistosomiasis MDA with praziquantel in seven endemic districts of the state, using a sub-district/ward-level implementation approach. Upon completion, we conducted desk reviews of field reports and a high-level stakeholder meeting among 95 key personnel involved in the MDA. We reviewed excerpts from the meetings to highlight the strengths, weaknesses, threats and opportunities (SWOT) of the sub-district/ward-level implementation approach. Quantitative data were summarized using basic descriptive statistics, while qualitative data were analyzed to identify emerging themes.ResultsAbout 1.45 million children between age 5 and 15 were targeted for treatment, and a geographic (100%) and therapeutic coverage of 85.5% was achieved. Therapeutic coverage was optimal (&gt;75%), across all the implementation districts (Range:76.2- 95.3%). Ifako-Ijaiye had the highest therapeutic coverage (95.3%), while Oshodi-Isolo as the least (76.2%). Strategies supporting high coverage includes; (1) adequate delineation of hard-to reach areas and allocation of commensurate resources, (2) improved consultation and microplanning among programmers, (3) addressing traffic congestion on transportation routes, (4) strengthened engagements and collaborations with community gatekeepers, (5) optimizing cash flow to mitigate financial risk, (6) capacity building of field stakeholders and, (7) regular advocacy and sensitization among stakeholders.ConclusionThis study provides possible directions for implementation of schistosomiasis control by programs and agencies at sub-district/ward-level in a cosmopolitan and urbanized state, like that of Lagos, Nigeria.
Taxonomic diversity of microbial communities in sub-seafloor hydrothermal sediments of the active Santorini-Kolumbo volcanic field
Authors: Polymenakou Paraskevi N. , Nomikou Paraskevi , Hannington Mark , Petersen Sven , Kilias Stephanos P. , Anastasiou Thekla I. , Papadimitriou Vasiliki , Zaka Eleutheria , Kristoffersen Jon Bent , Lampridou Danai , Wind Sandra , Heinath Verena , Lange Sabine , Magoulas Antonios 
Published: June 2023

IntroductionActive hydrothermal vents of volcanic origin provide a remarkable manifestation of life on Earth under extreme conditions, which may have consequences for our understanding of habitability on other terrestrial bodies as well.MethodsHere, we performed for the first time Illumina sequencing of bacterial and archaeal communities on sub-seafloor samples collected from the Santorini-Kolumbo volcanic field. A total of 19 (3-m long) gravity corers were collected and processed for microbial community analysis.ResultsFrom a total of 6,46,671 produced V4 sequences for all samples, a total of 10,496 different Operational Taxonomic Units (OTUs) were identified that were assigned to 40 bacterial and 9 archaeal phyla and 14 candidate divisions. On average, the most abundant phyla in all samples were Chloroflexi (Chloroflexota) (24.62%), followed by Proteobacteria (Pseudomonadota) (11.29%), Firmicutes (Bacillota) (10.73%), Crenarchaeota (Thermoproteota) (8.55%), and Acidobacteria (Acidobacteriota) (8.07%). At the genus level, a total of 286 known genera and candidate genera were mostly dominated by members of Bacillus, Thermoflexus, Desulfatiglans, Pseudoalteromonas, and Pseudomonas.DiscussionIn most of the stations, the Chao1 values at the deeper layers were comparable to the surface sediment samples denoting the high diversity in the subsurface of these ecosystems. Heatmap analysis based on the 100 most abundant OTUs, grouped the sampling stations according to their geographical location, placing together the two hottest stations (up to 99°C). This result indicates that this specific area within the active Kolumbo crater create a distinct niche, where microorganisms with adaptation strategies to withstand heat stresses can thrive, such as the endospore-forming Firmicutes.
Bacterial co-infection raises in-hospital mortality of COVID-19 patients: a retrospective study
Authors: Zong Kaican , Li Wen , Fu Yingya , Zhang Sha , Liu Yi , Li Shiying 
Published: June 2023

BackgroundWe aim to explore whether the bacterial co-infection with COVID-19 will raise the in-hospital mortality.MethodsCOVID-19 patients’ information were collected for analysis in our retrospective study. Neutrophil count and procalcitonin (PCT) were used to estimate whether there was a suspected bacterial co-infection.ResultsThe main baselines between the suspected bacterial infection (SBI) and no evidence of bacterial infection (NBI) groups were no significant differences. In SBI group, patients required more therapies than NBI group. There was significantly higher in-hospital mortality (26% vs.9%, P &lt; 0.001) between SBI and NBI groups in overall population. And in each subgroup based on pneumonia inflammation index (PII), it also showed higher in-hospital mortality of COVID-19 patients with bacterial co-infection. With logistic regression models, it showed that bacterial co-infection was associated with significantly higher in-hospital mortality in overall population (OR 1.694, 95% CI 1.179–2.434, p = 0.004) and mild subgroup (OR 2.374, 95% CI 1.249–4.514, p = 0.008). The rate of bacterial co-infection in overall population was 51%. At the same time, it showed a significantly higher rate of bacterial co-infection in critical subgroup than severe subgroup (63% vs. 49%, p = 0.003), and than that in moderate subgroup (63% vs. 48%, p = 0.002) based on clinical classification. It showed a significantly higher rates of bacterial co-infection in severe subgroup than moderate subgroup (66% vs. 49%, p = 0.001) based on PII. The result showed that the risk factor associated with significantly higher in-hospital mortality was PII (OR 1.018, 95%CI 1.012 to 1.024, P &lt; 0.001) with logistic regression models.InterpretationBacterial co-infection estimated by Neutrophil count and procalcitonin significantly raises in-hospital mortality of COVID-19 patients in overall population in our study. Its impact is more significant in mild and moderate PII subgroups. PII based on CT imaging combined with neutrophil count and PCT is beneficial for accurate differentiation of bacterial co-infection of COVID-19.
The dose–response relationship between smoking and the risk factor for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome
Authors: Dai Yan , Pu Qinqin , Hu Nannan , Zhu Jin , Han Yaping , Shi Ping , Li Jun , Jin Ke 
Published: June 2023

ObjectivesInvasive pulmonary aspergillosis (IPA) is common in immuno-compromised people, and a high incidence of IPA has been found in patients with severe fever with thrombocytopenia syndrome (SFTS). Our study aimed to determine the independent risk factors for IPA and the relationship between smoking status and the risk of IPA in SFTS patients.MethodsA retrospective analysis of SFTS patients in the First Affiliated Hospital of Nanjing Medical University from May 2011 to December 2021 was reviewed. The patients were divided into two groups: IPA and non-IPA groups. We compared demographic characteristics, clinical manifestation, laboratory parameters, treatment, and prognosis, and explored the risk factors of IPA using logistic regression and ROC curve. The dose-dependent effect of smoking on the risk of IPA was further estimated, including the age of smoking initiation, daily smoking amount, smoking duration, and pack-years of smoking.ResultsIn total, 189 individuals were included. Compared with the non-IPA group, the IPA group had higher levels of smoking, drinking, cough, dyspnea, aCCI scores, Dabie bandavirus (DBV) RNA load, ferritin, PCT, IL-6, APTT, LDH, BUN, creatinine, and lower levels of FT4 and TSH. The incidences of MODS, admission to ICU, ventilation, and broad-spectrum antibiotic treatment were significantly higher in the IPA group than in the non-IPA group. Multivariable logistic analysis showed that smoking history, cough, creatinine, admission to ICU, broad-spectrum, and corticosteroid therapies were the independent risk factors for IPA in SFTS patients. We further confirmed that the age of smoking initiation &lt;30 years, smoking at least one pack per day, smoking for at least 40 years, and having at least 40 pack-years of smoking exposure were the independent risk factors for IPA among smokers.ConclusionThe prognosis of SFTS patients in the IPA group is worse than that of the non-IPA group. Attention should be paid to SFTS patients with a smoking history, cough, creatinine, admission to ICU, and broad-spectrum and corticosteroid therapies. There is a strong dose-dependent association between smoking and IPA development in SFTS patients. Prophylactic antifungal therapy should be considered for SFTS patients with these risk factors, but further studies are necessary to determine if it is beneficial for the prognosis of these patients.
Identifying key multi-modal predictors of incipient dementia in Parkinson’s disease: a machine learning analysis and Tree SHAP interpretation
Authors: McFall G. Peggy , Bohn Linzy , Gee Myrlene , Drouin Shannon M. , Fah Harrison , Han Wei , Li Liang , Camicioli Richard , Dixon Roger A. 
Published: June 2023

BackgroundPersons with Parkinson’s disease (PD) differentially progress to cognitive impairment and dementia. With a 3-year longitudinal sample of initially non-demented PD patients measured on multiple dementia risk factors, we demonstrate that machine learning classifier algorithms can be combined with explainable artificial intelligence methods to identify and interpret leading predictors that discriminate those who later converted to dementia from those who did not.MethodParticipants were 48 well-characterized PD patients (Mbaseline age = 71.6; SD = 4.8; 44% female). We tested 38 multi-modal predictors from 10 domains (e.g., motor, cognitive) in a computationally competitive context to identify those that best discriminated two unobserved baseline groups, PD No Dementia (PDND), and PD Incipient Dementia (PDID). We used Random Forest (RF) classifier models for the discrimination goal and Tree SHapley Additive exPlanation (Tree SHAP) values for deep interpretation.ResultsAn excellent RF model discriminated baseline PDID from PDND (AUC = 0.84; normalized Matthews Correlation Coefficient = 0.76). Tree SHAP showed that ten leading predictors of PDID accounted for 62.5% of the model, as well as their relative importance, direction, and magnitude (risk threshold). These predictors represented the motor (e.g., poorer gait), cognitive (e.g., slower Trail A), molecular (up-regulated metabolite panel), demographic (age), imaging (ventricular volume), and lifestyle (activities of daily living) domains.ConclusionOur data-driven protocol integrated RF classifier models and Tree SHAP applications to selectively identify and interpret early dementia risk factors in a well-characterized sample of initially non-demented persons with PD. Results indicate that leading dementia predictors derive from multiple complementary risk domains.
Brain age prediction using the graph neural network based on resting-state functional MRI in Alzheimer's disease
Authors: Gao Jingjing , Liu Jiaxin , Xu Yuhang , Peng Dawei , Wang Zhengning 
Published: June 2023

IntroductionAlzheimer's disease (AD) is a neurodegenerative disease that significantly impacts the quality of life of patients and their families. Neuroimaging-driven brain age prediction has been proposed as a potential biomarker to detect mental disorders, such as AD, aiding in studying its effects on functional brain networks. Previous studies have shown that individuals with AD display impaired resting-state functional connections. However, most studies on brain age prediction have used structural magnetic resonance imaging (MRI), with limited studies based on resting-state functional MRI (rs-fMRI).MethodsIn this study, we applied a graph neural network (GNN) model on controls to predict brain ages using rs-fMRI in patients with AD. We compared the performance of the GNN model with traditional machine learning models. Finally, the post hoc model was also used to identify the critical brain regions in AD.ResultsThe experimental results demonstrate that our GNN model can predict brain ages of normal controls using rs-fMRI data from the ADNI database. Moreover the differences between brain ages and chronological ages were more significant in AD patients than in normal controls. Our results also suggest that AD is associated with accelerated brain aging and that the GNN model based on resting-state functional connectivity is an effective tool for predicting brain age.DiscussionOur study provides evidence that rs-fMRI is a promising modality for brain age prediction in AD research, and the GNN model proves to be effective in predicting brain age. Furthermore, the effects of the hippocampus, parahippocampal gyrus, and amygdala on brain age prediction are verified.
Eicosapentaenoic acid and branched-chain amino acids fortified complete nutrition drink improved muscle strength in older individuals with inadequate protein intake
Authors: Khoonin Watcharapol , Shantavasinkul Prapimporn Chattranukulchai , Santivarangkna Chalat , Praengam Kemika , Trachootham Dunyaporn 
Published: June 2023

BackgroundElevated inflammation and negative nutritional balance contribute to sarcopenia, a progressive loss of muscle mass, strength, and function. This study investigated the effect of energy supplementation and the combination of anti-inflammatory factor (eicosapentaenoic acid; EPA) and muscle-synthesis promotor (branched-chain amino acids; BCAA) on body composition, muscle, and inflammatory biomarkers in elderly with inadequate protein intake.MethodsA randomized blinded placebo-controlled trial was conducted on 84 elderly with inadequate protein intake. The participants were randomly assigned into four groups receiving a complete nutrition drink; (1) control formula, (2) fortified with 2.2 g EPA, (3) with 2.2 g EPA and 5 g BCAA (2:1:1 of Leu: Ile: Val), and (4) with 2.2 g EPA plus 5g BCAA (4:1:1 of Leu: Ile: Val). Each subject consumed two sachets of the drink to gain 500 kcal/day and performed arm muscle exercises for 3 weeks. Body compositions and handgrip strength were measured using BIA and a dynamometer, respectively. Plasma EPA and BCAA levels were determined using LC-MS/MS to ensure compliance. Muscle protein biomarkers including histidine, β-alanine, and carnosine were measured using LC-MS/MS. Serum inflammatory (IL-6) and anti-inflammatory cytokines (IL-10) were measured by using ELISA.ResultsNo symptoms and signs of adverse events were observed. The right arm muscle mass and handgrip strength were significantly increased after consuming a complete nutrition drink fortified with EPA + BCAA 2:1:1 and 4:1:1 of Leu: Ile: Val (p &lt; 0.05 and p &lt; 0.01, respectively. Consistently, consuming such combinatory formula non-significantly elevated carnosine with reduced histidine, and increased IL-10 with decreased IL-6. All relevant intervention groups showed a significant increase in plasma levels of BCAA and EPA.ConclusionConsuming a complete nutrition drink fortified with 2.2g EPA and 5g BCAA 2:1:1 or 4:1:1 of Leu: Ile: Val for 3 weeks may increase right arm muscle mass and strength in elderly with inadequate protein intake. The tendency of increased dipeptide (carnosine)/decreased free amino acid (histidine) suggests a shift toward muscle protein synthesis. The trend of decreased inflammatory/increased anti-inflammatory cytokines suggests an anti-inflammatory effect. Future long-term studies are warranted to confirm the combinatory effect of BCAA and EPA in the prevention of sarcopenia.Clinical trial registrationThailand Clinical Trial Registry No. TCTR20230116005.
Effects of 8 weeks of resistance training in combination with a high protein diet on body composition, muscular performance, and markers of liver and kidney function in untrained older ex-military men
Authors: Bagheri Reza , Shakibaee Abolfazl , Camera Donny M. , Sobhani Vahid , Ghobadi Hamid , Nazar Eisa , Fakhari Hadi , Dutheil Fred 
Published: June 2023

BackgroundThe effects of a high protein diet in combination with chronic resistance training (RT) on skeletal muscle adaptation responses in untrained older ex-military men is unknown. Therefore, we compared the effects of 8 weeks of RT in combination with either a high (1.6 g/kg/d) or low protein diet (0.8 g/kg/d) on body composition [skeletal muscle mass (SMM) and body fat percentage (BFP)], muscular strength, power, and endurance (upper and lower body), markers of liver [alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)] and kidney (creatinine and urea) function, and lipid profile low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cholesterol levels in a cohort of healthy, untrained older ex-military males.MethodsForty healthy untrained older ex-military males (age: 61 ± 2 yr, body mass index: 23.2 ± 1.3 kg.m−2) performed 8 weeks (three sessions·w−1) of RT with either 1.6 g/kg/d (RHP; n = 20) or 0.8 g/kg/d of protein (RLP; n = 20). Body composition (assessed by Inbody 720), muscular strength (1-RM for chest and leg press), power (Wingate test), endurance (75% 1-RM for chest and leg press), and markers of liver and kidney function (biochemical kits) were assessed pre and post-intervention.ResultsSMM and muscular strength (upper and lower body) increased post-intervention in both groups and were significantly greater in RHP compared to RLP, while muscular power increased to the same extent in both groups (p &lt; 0.05) with no between-group differences (p &gt; 0.05). In contrast, there were no post-intervention changes in muscular endurance, HDL, and BFP remained in either group (p &gt; 0.05). ALT and creatinine significantly increased in RHP compared to RLP while GGT, AST, and urea only increased in the RLP group (p &lt; 0.05). LDL and cholesterol significantly decreased in both groups (p &lt; 0.05).ConclusionA daily intake of 1.6 g/kg/d protein was superior to 0.8 g/kg/d (current recommended daily intake) for promoting greater improvements in SMM and muscle strength and thus may be a more suitable level of intake for promoting such adaptive responses. Notwithstanding observed between-group differences in ALT and creatinine and the fact that levels remained within normal ranges, it is feasible to conclude that this daily protein intake is efficacious and well tolerated by healthy, untrained older ex-military males.