bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell type and sex specific mitochondrial phenotypes in iPSC derived models of Alzheimer’s disease
Authors: Flannagan Kaitlin , Stopperan Julia A. , Hauger Brittany M. , Troutwine Benjamin R. , Lysaker Colton R. , Strope Taylor A. , Csikos Drummond Vivien , Gilmore Caleb A. , Swerdlow Natalie A. , Draper Julia M. , Gouvion Cynthia M. , Vivian Jay L. , Haeri Mohammad , Swerdlow Russell H. , Wilkins Heather M. 
Published: August 2023

IntroductionMitochondrial dysfunction is observed in Alzheimer’s disease (AD). Altered mitochondrial respiration, cytochrome oxidase (COX) Vmax, and mitophagy are observed in human subjects and animal models of AD. Models derived from induced pluripotent stem cells (iPSCs) may not recapitulate these phenotypes after reprogramming from differentiated adult cells.MethodsWe examined mitochondrial function across iPSC derived models including cerebral organoids, forebrain neurons, and astrocytes. iPSCs were reprogrammed from fibroblasts either from the University of Kansas Alzheimer’s Disease Research Center (KU ADRC) cohort or purchased from WiCell. A total of four non-demented and four sporadic AD iPSC lines were examined. Models were subjected to mitochondrial respiration analysis using Seahorse XF technology, spectrophotometric cytochrome oxidase (COX) Vmax assays, fluorescent assays to determine mitochondrial mass, mitochondrial membrane potential, calcium, mitochondrial dynamics, and mitophagy levels. AD pathological hallmarks were also measured.ResultsiPSC derived neurons and cerebral organoids showed reduced COX Vmax in AD subjects with more profound defects in the female cohort. These results were not observed in astrocytes. iPSC derived neurons and astrocytes from AD subjects had reduced mitochondrial respiration parameters with increased glycolytic flux. iPSC derived neurons and astrocytes from AD subjects showed sex dependent effects on mitochondrial membrane potential, mitochondrial superoxide production, and mitochondrial calcium. iPSC derived neurons from AD subjects had reduced mitochondrial localization in lysosomes with sex dependent effects on mitochondrial mass, while iPSC derived astrocytes from female AD subjects had increased mitochondrial localization to lysosomes. Both iPSC derived neurons and astrocytes from AD subjects showed altered mitochondrial dynamics. iPSC derived neurons had increased secreted Aβ, and sex dependent effects on total APP protein expression. iPSC derived astrocytes showed sex dependent changes in GFAP expression in AD derived cells.ConclusionOverall, iPSC derived models from AD subjects show mitochondrial phenotypes and AD pathological hallmarks in a cell type and sex dependent manner. These results highlight the importance of sex as a biological variable in cell culture studies.
Prognostic values of geriatric nutrition risk index on elderly patients after spinal tuberculosis surgery
Authors: Huang Yong , Wu Ruibang , Xia Qinghong , Liu Limin , Feng Ganjun 
Published: August 2023

BackgroundSpinal tuberculosis (STB) is a significant public health concern, especially in elderly patients, due to its chronic and debilitating nature. Nutritional status is a critical factor affecting the prognosis of STB patients. The geriatric nutritional risk index (GNRI) has been established as a reliable predictor of adverse outcomes in various diseases, but its correlation with surgical outcomes in elderly STB patients has not been studied.ObjectiveThe study aimed to assess the prognostic value of the GNRI in elderly patients with STB who underwent surgery.MethodsWe conducted a retrospective analysis of medical records of elderly patients (65 years or older) diagnosed with active STB who underwent surgical treatment. Data collection included patient demographics, comorbidities, clinical history, laboratory testing, and surgical factors. GNRI was calculated using serum albumin levels and body weight. Postoperative complications were observed and recorded. The patients were followed up for at least 1 year, and their clinical cure status was assessed based on predefined criteria.ResultsA total of 91 patients were included in the study. We found that a GNRI value of &lt;98.63 g/dL was a cutoff value for predicting unfavorable clinical prognosis in elderly STB patients undergoing surgery. Patients with a low GNRI had higher Charlson Comorbidity Index scores, were more likely to receive red blood cell transfusions, and had a higher prevalence of overall complications, particularly pneumonia. The unfavorable clinical prognosis group had lower GNRI scores compared to the favorable prognosis group. Multivariate analysis showed that lower GNRI independently predicted unfavorable clinical outcomes in elderly STB patients.ConclusionThe study concluded that the GNRI is a valuable biomarker for predicting prognosis in elderly STB patients undergoing surgical intervention. Patients with lower GNRI scores had worse outcomes and a higher incidence of complications.
Identification of broadly-conserved parasitic nematode proteins that activate immunity
Authors: Rosa Bruce A. , Zarlenga Dante S. , Fournet Valsin M. , Beshah Ethiopia , Hill Dolores E. , Zarlenga Alexander , Yee Angela , Liang Xiaowu , Shandling Adam D. , Oberai Amit , Urban Joseph F. , Mitreva Makedonka 
Published: August 2023

IntroductionSoil transmitted nematodes are impediments to human health and agricultural production. Poor anthelmintic efficiencies, the emergence of resistant strains, and the persistence of infective stages highlight the need for more effective control strategies. Parasitic nematodes elicit a Th2-type immune response that most often is not protective. Vaccination has thus far been unsuccessful due to unrealized antigenic characters and unknown mechanisms that nematodes use to circumvent host immunity.MethodsHere, we used a genomics/proteomics approach (including immunoblot experiments from pigs infected with T. suis) to prioritize putative immunogenic excretory/secretory (E/S) proteins conserved across and specific to several gastrointestinal (GI) parasitic nematode species. A cocktail of five recombinant proteins optimized for conserved GI nematode targets was used immunize pigs and test for active antibody responses in both the serum and intestinal ileal fluid of immunized pigs. An antibody-protein array of putative immunogenic proteins was developed from a combined bioinformatic, experimental, and literature-based prioritization of homologous parasite proteins.ResultsScreening the array with sera and ileal fluid samples from immunized pigs suggested cross-reactivity among homologous proteins and a general activation of immunity. PCA clustering showed that the overall immune responses were altered by immunization, but no substantial changes were observed following direct worm challenge with either Ascaris suum or Trichuris suis.DiscussionProteins that activated immunity are potential antigens for immunization and the multi-omics phylum-spanning prioritization database that was created is a valuable resource for identifying target proteins in a wide array of different parasitic nematodes. This research strongly supports future studies using a computational, comparative genomics/proteomics approach to produce an effective parasite vaccine.
Effects of infection control measures towards preventing SARS-CoV-2 outbreaks in a German choir boarding school from March 2020 to April 2022
Authors: Lampl Benedikt M. J. , Schöberl Patricia , Atzenbeck Noah , Erdl Michael , Dillitzer Nepomuk , Wallbrecher Jakov , Weigl Marcus , Sauer Michael , Kheiroddin Parastoo , Niggel Jakob , Mauerer Richard , Ambrosch Andreas , Kabesch Michael 
Published: August 2023

BackgroundSinging in a choir was associated with larger outbreaks in the beginning of the SARS-CoV-2 pandemic.Materials and methodsWe report on the effect and acceptance of various infection control measures on the occurrence of SARS-CoV-2 infections in the world famous Domspatzen boys' choir from March 2020 to April 2022.ResultsIn addition to basic general hygiene measures, systematic rRT-PCR testing and scientifically approved concepts of distancing during singing were applied. While single infections of choir members could not be avoided, singing-related outbreaks were not observed. Until the Omicron variant emerged, potential transmission of SARS-CoV-2 in the school was limited to only one case. Incidences at the school were never higher than in the comparable general population until then. While the impact of the pandemic on daily life and singing was rated as severe, especially by staff members, most students agreed with the usefulness of protection measures and rated them as acceptable. Students viewed regular testing as the most important tool to increase safety in the school.DiscussionA bundle of infection control measures including regular testing can prevent outbreaks of SARS-CoV-2 even in the setting of choir singing. Measures are acceptable for choir members if they allow to continue with singing and performing.
Evaluation of the effect of direct-acting antiviral agents on melatonin level and lipid peroxidation in chronic hepatitis C patients
Authors: El-Mahdy Nageh Ahmed , Abou-Saif Sabry , Abd EL hamid Medhat Ismail , Hashem Heba M. , Hammad Mohamed Anwar , Abu-Risha Sally El-Sayed 
Published: August 2023

Background: Oxidative stress and its end products, such as malondialdehyde (MDA) play a leading role in the pathogenesis of hepatitis C. Melatonin is a hormone that helps regulate circadian rhythms, which likely play a role in infectious diseases in terms of susceptibility, clinical expression, and outcome.Objective: The present study was conducted to assess serum malondialdehyde and melatonin levels in patients with chronic hepatitis C infection before and after the intake of direct-acting antivirals.Method: Forty hepatitis C patients were the subjects of this study. While ten healthy volunteers who matched in age and socioeconomic status served as the control subjects. Malondialdehyde and melatonin were assayed in the serum of the three groups, and the results were statistically analyzed.Results: Hepatitis C patients had significantly higher malondialdehyde (p &lt; 0.001) but significantly lower melatonin (p &lt; 0.001) as compared to the healthy controls. After 12 weeks of treatment with direct-acting antivirals, the malondialdehyde level decreased significantly (p &lt; 0.001) and the melatonin level increased significantly (p &lt; 0.001). A significant negative correlation between malondialdehyde and melatonin was observed.Conclusion: The present findings suggest that treatment of hepatitis C patients with Direct-acting antivirals improves liver function parameters and antioxidant profiles.
The immune and metabolic treatment approach of using testosterone on mice models of liver injury
Authors: Amer Johnny , Salhab Ahmad , Snobar Hadeel , Alhabil Yazan 
Published: August 2023

Background: Natural killer (NK) cells showed an anti-fibrotic effect; however, their function is thought to be impaired in advanced liver injury. In the current study, we aimed to assess the immune and metabolic impact of testosterone on mice models of liver injury.Methods: Carbon-tetrachloride induced liver fibrosis male mice models was i.p injected for 2 weeks (acute) and 4 weeks (chronic) (n = 36). Testosterone (4 mg/kg mouse body weight) was injected i.p. following the first week of the acute model of CCl4 and following the second week of the chronic model of CCl4. At the end of the experiments, mice were sacrificed, and serum was collected for assessing liver enzymes of ALT and AST, as well as inflammatory markers of IL-6, metabolic makers of C-peptide levels, and lipid and glucose profiles. Livers were harvested and used for histological assessments for inflammation and fibrosis. Fibrosis profiles from liver extracts, αSMA and Collagen III, were assessed by RT-PCR. Moreover, liver tissue-resident NK cells were isolated and evaluated for their activity by assessing INF-γ and IL-6 receptors using ELISA and flow cytometry, respectively.Results: Serum ALT, AST, and IL-6, as well as metabolic assessments of cholesterol, triglyceride, C-peptide, fasting blood sugar, and fibrotic profiles, were linearly correlated with disease progressions. Histological characterization of the liver was worsened in the chronic model of liver injury. Testosterone-treated mice exhibit a significant reduction in collagen depositions with less dense fibrosis tissue associated with reduced liver injury enzymes and metabolic markers in both the acute and chronic CCl4 mice models in favor of the latter one (p &lt; 0.05). Moreover, testosterone treatments displayed a significant decrease in serum IL-6 of 2.4-fold (p = 0.0001) and 2.3-fold (p = 0.0003) in the acute and chronic models, respectively (p = 0.002), and data showed an increase in INF-γ release from NK associated with a reduction in their IL-6 receptor expressions (p &lt; 0.05).Conclusion: Our results indicated effects of testosterone on mediating a decreased expressions of NK IL-6 receptors and consequently inducing their activation; which in part, could explain the amelioration of liver injury. Our data suggest an anti-inflammatory and anti-fibrotic treatment approach of using testosterone for delaying disease progressions.
Risk of herpes zoster associated with JAK inhibitors in immune-mediated inflammatory diseases: a systematic review and network meta-analysis
Authors: Xu Qingling , He Liyuan , Yin Yufeng 
Published: August 2023

Objective: Janus kinase (JAK) inhibitors are a novel class of drugs that have shown efficacy in treating immune-mediated inflammatory diseases (IMIDs). However, their safety profile in terms of herpes zoster infection remains unclear. We aimed to evaluate the risk of herpes zoster associated with JAK inhibitors in patients with IMIDs.Methods: A systematic search of electronic databases was conducted to identify randomized controlled trials (RCTs) that evaluated the safety of JAK inhibitors in patients with IMIDs including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriasis (PsO), and psoriatic arthritis (PsA). The primary outcome of interest was the incidence of herpes zoster infection. Network meta-analysis was performed to compare the risk of herpes zoster among different JAK inhibitors and placebo.Results: A network meta-analysis was conducted using data from 47 RCTs including 24,142 patients. In patients with IMIDs, peficitinib 100 mg QD was associated with the highest risk of herpes zoster infection in patients with IMIDs, followed by baricitinib 4 mg QD and upadacitinib 30 mg QD. No difference in herpes zoster risk was found for other JAK inhibitors compared with placebo. Subgroup analysis indicated that higher incidence of herpes zoster was found in patients treated by baricitinib 4 mg QD, peficitinib 100 mg QD, and upadacitinib 30 mg QD only in patients with RA.Conclusion: Our study suggests that some JAK inhibitors, particularly peficitinib, baricitinib, and tofacitinib, are associated with a higher risk of herpes zoster infection in patients with IMIDs.
Can a personalised music listening intervention decrease agitation in hospitalised patients with dementia? A feasibility trial
Authors: Lee Shanna , Chan Lily , Maddison John 
Published: August 2023

IntroductionAgitation is a common manifestation of the behavioural and psychological symptoms of dementia (BPSD). Pharmacotherapy is not the first-line management because of its potential harms, particularly in the elderly. Music as a non-pharmacological intervention for agitation has been explored in residential aged-care facilities, but few studies have been situated in hospitals. This pilot aims to evaluate the feasibility of a personalised music listening intervention for reducing agitation in hospitalised patients with dementia in a metropolitan Geriatric Evaluation and Management (GEM) unit.MethodsTwo-arm randomised control feasibility trial. Eligible patients were assigned to the music intervention or control group, with the intervention group receiving music daily between 15:00–16:00, and agitation levels measured in both groups hourly based on the Pittsburgh Agitation Score (PAS) over 5 days of hospitalisation. Post-trial semi-structured interviews assessed feasibility of the intervention.ResultsTwenty-one patients were recruited over 8 months. Interviews with staff involved indicated that the music intervention was manageable to deliver, assisted engagement with patients which increased efficiency of some clinical tasks, and challenged staff mindset around using psychotropic medication to address agitation. PAS results were inconclusive, because of underpowered numbers in this pilot study.ConclusionIt is feasible for nursing staff to deliver a personalised music listening intervention to patients with dementia in a geriatric unit of a tertiary hospital, without compromising on usual clinical care.
Optomyography-based sensing of facial expression derived arousal and valence in adults with depression
Authors: Broulidakis M. John , Kiprijanovska Ivana , Severs Liberty , Stankoski Simon , Gjoreski Martin , Mavridou Ifigeneia , Gjoreski Hristijan , Cox Sophia , Bradwell Daisy , Stone James M. , Nduka Charles 
Published: August 2023

BackgroundContinuous assessment of affective behaviors could improve the diagnosis, assessment and monitoring of chronic mental health and neurological conditions such as depression. However, there are no technologies well suited to this, limiting potential clinical applications.AimTo test if we could replicate previous evidence of hypo reactivity to emotional salient material using an entirely new sensing technique called optomyography which is well suited to remote monitoring.MethodsThirty-eight depressed and 37 controls (≥18, ≤40 years) who met a research diagnosis of depression and an age-matched non-depressed control group. Changes in facial muscle activity over the brow (corrugator supercilli) and cheek (zygomaticus major) were measured whilst volunteers watched videos varying in emotional salience.ResultsAcross all participants, videos rated as subjectively positive were associated with activation of muscles in the cheek relative to videos rated as neutral or negative. Videos rated as subjectively negative were associated with brow activation relative to videos judged as neutral or positive. Self-reported arousal was associated with a step increase in facial muscle activation across the brow and cheek. Group differences were significantly reduced activation in facial muscles during videos considered subjectively negative or rated as high arousal in depressed volunteers compared with controls.ConclusionWe demonstrate for the first time that it is possible to detect facial expression hypo-reactivity in adults with depression in response to emotional content using glasses-based optomyography sensing. It is hoped these results may encourage the use of optomyography-based sensing to track facial expressions in the real-world, outside of a specialized testing environment.
Advocating for children's surgery within country health plans: lessons from Nigeria and the global stage
Authors: Seyi-Olajide Justina O. , Faboya Omolara , Williams Omolara , Lakhoo Kokila , Ameh Emmanuel A. 
Published: August 2023

BackgroundDespite the growing emphasis on provision of quality safe and affordable surgical care in low- and middle-income countries, and the World Health Assembly resolution 68. 15 on strengthening emergency and essential surgical care and anesthesia as components of universal health coverage, a review of published surgical plans of various countries, revealed a lack of emphasis on children's surgery. Due to the peculiarities of the human resource, infrastructure and equipment required for children's surgery, a lack of deliberate actions and policies targeted at strengthening surgical care for children implies that achieving universal health coverage for children may not be a reality in this setting.MethodsA baseline assessment of children's surgical capacity was conducted in Nigeria as a part of the National Surgical Obstetrics Anesthesia and Nursing Plan (NSOANP) process. The assessment was done using the World Health Organization (WHO) hospital assessment tool modified for children's surgery (Children Surgical Assessment Tool).ResultsSignificant infrastructural gaps were found, with an abysmally low density of pediatric surgeons and anaesthesiologists, poor emergency preparedness, lack of reliable surgical data and non-inclusion of children's surgery in the national strategic health plan. Using the Global Initiative for Children's Surgery's (GICS) Optimal Resources for Children's Surgical Care (OReCS) document and focusing on the strategic goals and priorities, children's surgery was incorporated into the NSOANP. Implementation of the plan is currently ongoing.ConclusionFrom Nigeria's experience, appropriate advocacy and inclusion of children surgery providers in policy making will promote prioritization of children's surgery in country health and surgical plans.
Enhancing Student Wellbeing Through Social Prescribing: A Rapid Realist Review
Authors: Davies Mark , Elliott Megan , Wallace Sarah , Wallace Carolyn 
Published: August 2023

Objectives: A Rapid Realist Review of social prescribing in Higher Education (HE) was undertaken to determine what works, for whom, how, why, and within what circumstances. The review resulted in the development of a Realist Programme Theory articulating the way in which social prescribing can be implemented within the HE environment.Methods: Searches of 12 electronic databases were supplemented by citation chaining and grey literature surfaced by the Project Advisory Group. The RAMESES Quality Standards for Realist Review were followed, and the retrieved articles were systematically screened and iteratively analysed to develop Context-Mechanism-Outcome Configurations (CMOCs) and an overarching Realist Programme Theory.Results: A total of 57 documents were included. The overarching programme theory was developed from the analysis of these documents and comprised of a social prescribing pathway with the following components: (1) An Accessible Gateway, (2) A Skilled Peer, (3) Trusted-Safe-Credible Resources, and (4) A Healthy Setting.Conclusion: A Realist Programme Theory was developed—this model and associated principles will provide a theoretical basis for the implementation of social prescribing pathways within higher education. Whilst the direct project outputs are of particular significance to the UK HE audience, the underpinning principles can support practice within the global arena.