bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of pegylated interferon α-2b-based immunotherapy for inactive hepatitis B surface antigen carriers
Authors: Ning Huibin , Li Kuan , Peng Zhen , Jin Huiming , Zhao Hong , Shang Jia 
Published: August 2023

Objectives
Pegylated interferon α-2b (PegIFNα-2b) therapy can help inactive hepatitis B surface antigen (HBsAg) carriers (IHCs) achieve clinical cure. To explore and compare the efficacy, safety, and relevant influential factors of PegIFNα-2b monotherapy and PegIFNα-2b-based immunotherapy for IHCs.

Methods
This exploratory, prospective, single-center, randomized controlled trial enrolled 40 IHCs who were randomized into group A (PegIFNα-2b treatment for 68 weeks) and group B (two cycles of PegIFNα-2b treatment with a lead-in period of GM-CSF and vaccine treatment before each cycle). The primary endpoint was 68-week HBsAg loss rate.

Results
At week 68, the HBsAg loss rates were 45.45% [full analysis set (FAS)] and 46.67% [per-protocol set (PPS)]. There was no statistically significant difference in HBsAg loss rate between groups A and B (P > 0.05). Univariate analysis revealed that age ≤40 years old, baseline HBsAg <200 IU/ml, and 24-week HBsAg decline ≥2 log10 IU/ml were significantly associated with HBsAg loss in FAS population (P < 0.05). Multivariate analysis showed that only 24-week HBsAg decline ≥2 log10 IU/ml was the independent influencing factor in both FAS and PPS populations (P < 0.05). The adverse events were common and mild, and the therapies were well-tolerated.

Conclusion
Treatment of IHCs with PegIFNα-2b-based therapy could result in a high HBsAg loss rate. The HBsAg loss rate of combined immunotherapy was similar to that of PegIFNα-2b monotherapy, and the safety was good.

ClinicalTrials.gov ID:
NCT05451420.
The prognostic value of 99mTc-glucosamine imaging in patients with rheumatoid arthritis: a single center prospective study
Authors: Evbuomwan Osayande , Engelbrecht Gerrit , Driver Cathryn , Jansen van Rensburg Barend , Labuschagne Mathys , Horn-Lodewyk Je’nine 
Published: August 2023

Objectives
Poor prognostic factors in rheumatoid arthritis (RA) are associated with a more severe form of the disease. Nuclear medicine functional imaging has shown remarkable merit at identifying active disease in patients with RA and is increasingly being used in this regard. However, its prognostic value has not been evaluated thoroughly. We aimed to assess the prognostic value of technetium-99m (99mTc-) glucosamine imaging in patients with RA.

Methods
Twenty-two participants diagnosed by an experienced rheumatologist with RA were recruited for inclusion in the study. Blood samples were obtained from each participant for baseline C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody titer. On the same day, each participant was injected with 20–25 millicurie (mCi) of 99mTc-glucosamine. Planar and single-photon emission computed tomography images of known disease sites were acquired up to 2 hours after radiopharmaceutical administration. Affected joints were qualitatively assessed and graded for 99mTc-glucosamine uptake and compared with blood results.

Results
All participants affected joints had an increased uptake of the radiopharmaceutical, with 14 (63.6%) having elevated RF and anti-CCP antibody titers. Eight of the 14 patients with increased RF and anti-CCP antibodies had grade 3 uptake of 99mTc-glucosamine. The remaining 6 had grade 2 uptake. A significant correlation between higher grade uptake and increased levels of RF and anti-CCP antibodies (P = 0.031) was observed.

Conclusion
We found a strong correlation between high-grade disease on imaging and the presence of RF and anti-CCP antibodies in patients with RA.
The effect of burnout syndrome on the job satisfaction of employees in the municipalities of South Lima: a cross-sectional study
Authors: Pacheco Alex , Alvarez Ana , Peñaranda Cesar , Pineda Flor , Quispe Julio , Felix-Poicon Edwin , Ruiz Mario 
Published: August 2023

Introduction and importance:Nowadays, improving the performance of employees is essential to increase productivity and achieve continuous improvement; therefore, it is necessary to achieve job satisfaction among all members of the organisation to avoid negative attitudes, professional burnout, health problems and a lack of commitment. Therefore, our objective was to determine the level of burnout and its relationship with the level of job satisfaction among employees in the municipalities of southern Lima.Methods:The research is basic research, with a quantitative approach and a cross-sectional, nonexperimental, correlational design. The survey technique was used and the data collection instrument was a questionnaire addressed to 271 workers of the municipalities of South Lima on the variable burnout syndrome with the dimensions depersonalisation and emotional exhaustion, as well as on the variable job satisfaction with the dimensions work benefits, administrative policies and social relations, with a Cronbach’s alpha reliability of 0.801.Results:The results show that 50.2% of the employees state that they have an overload of mental effort that causes a high level of emotional exhaustion, 50.2% state that the work develops in them negative and insensitive attitudes that increase their level of depersonalisation and 77.9% state that the company is unable to satisfy the personal demands of the employees through the work benefits it offers.Conclusions:These findings reflect that burnout is a common illness in organisations due to workload, poor organisational climate and neglect of employees’ emotional health. Therefore, more research is needed on the role of organisations in reducing levels of occupational burnout in order to promote improvements in mental health.
Pachydermoperiostosis: a case report of initial improvement with etoricoxib
Authors: Vaidya Nirish , Acharya Nabaraj , Katila Shreesuna , Adhikari Samyog , Pandey Urmila 
Published: August 2023

Introduction and importance:
Pachydermoperiostosis (PDP) is a syndrome characterised by the triad of pachydermia, digital clubbing and periostosis of long bones and its scarce incidence and similarity in clinical features with acromegaly makes the diagnosis challenging. The elevated PGE2 levels have been hypothesised as one of its mechanisms and therapies have been targeted to inhibit this prostaglandin.

Case presentation:
A 25-year-old man with no comorbidities presented to OPD with a 10-year history of bilateral pain and swelling of the hands and feets associated with hyperhidrosis, grade IV clubbing and marked skin thickening on his forehead. X-rays revealed hyperostosis of the metacarpals, proximal and middle phalanges and periosteal bone formation with cortical thickening of the ankle joint. Tests done to rule out differentials such as thyroid acropachy, acromegaly, psoriatic arthritis were normal and a clinical diagnosis of PDP, a rare genetic disease characterised by pachyderma, digital clubbing and periostosis was made.

Clinical discussion:
The patient was managed conservatively with etoricoxib for 6 months on a follow-up basis. The symptoms were improving and a repeat X-ray showed partial improvement of soft tissue thickening and periostosis.

Conclusion:
PDP is a rare diagnosis with no clear consensus on a management approach. Its management with selective COX-2 inhibitors such as etoricoxib should be considered but its long-term effects should be studied further.
Imaging of Fontan-Associated Liver Disease
Authors: Brown Mark J. , Kolbe Amy B. , Hull Nathan C. , Hilscher Moira , Kamath Patrick S. , Yalon Mariana , Gu Chris N. , Amawi Ali Dean T. , Venkatesh Sudhakar K. , Wells Michael L. 
Published: August 2023

Abstract
The Fontan procedure is the definitive treatment for patients with single-ventricle physiology. Surgical advances have led to a growing number of patients surviving into adulthood. Fontan-associated liver disease (FALD) encompasses a spectrum of pathologic liver changes that occur secondary to altered physiology including congestion, fibrosis, and the development of liver masses. Assessment of FALD is difficult and relies on using imaging alongside of clinical, laboratory, and pathology information. Ultrasound, computed tomography, and magnetic resonance imaging are capable of demonstrating physiologic and hepatic parenchymal abnormalities commonly seen in FALD. Several novel imaging techniques including magnetic resonance elastography are under study for use as biomarkers for FALD progression. Imaging has a central role in detection and characterization of liver masses as benign or malignant. Benign FNH-like masses are commonly encountered; however, these can display atypical features and be mistaken for hepatocellular carcinoma (HCC). Fontan patients are at elevated risk for HCC, which is a feared complication and has a poor prognosis in this population. While imaging screening for HCC is widely advocated, no consensus has been reached regarding an optimal surveillance regimen.
<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">A rare and fatal case of tubo-ovarian abscess due to&#160;<em>Burkholderia pseudomallei</em>&#160;presenting as puerperal sepsis
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Authors: Bhaskar M Maanasa , Rajamanikam Soundarya , Raj Sruthi , Sistla Sujatha , Nichanahalli Kubera Siddappa 
Published: August 2023

Introduction : Melioidosis is an emerging life threatening infectious disease caused by Gram negative bacilli Burkholderia pseudomallei found in contaminated soil and surface ground water . It often presents with varied clinical manifestations and has a high mortality if left untreated due to lack of clinical suspicion. Here we report a rare and fatal case of puerperal sepsis due to Burkholderia pseudomallei in a young woman.
Case report: A 25-year-old female comes to a medical consultation at day 43 post partum with complains of fever on and off for the past 40 days associated with vomiting. On per speculum examination, greenish discharge from the cervix was seen and a right adnexal mass was felt which was cystic in consistency, non-tender and pushing cervix to the left side. Exploratory laparotomy was carried out and pus was drained from below the rectus sheath, and from right tubo-ovarian mass. Peripheral blood sample and the pus samples collected intraoperatively grew Burkholderia pseudomallei . The patient expired on the 5 th post operative day due to septic shock with disseminated intravascular coagulation secondary to puerperal sepsis.
Conclusion: Melioidosis is a fatal but treatable disease when it is promptly diagnosed. In a country like India, where tuberculosis is highly endemic, underdiagnosis of melioidosis can be a common consequence. Clinicians and Microbiologists should have high index of suspicion especially in individuals with underlying illness.
Showing the limitations of available phenotypic assays to detect B. pseudomallei from clinical specimens in Nigeria
Authors: Orababa Oluwatosin Qawiyy , Adesida Solayide A. , Peters Rebecca F. , AbdulGanniyu Zainab , Olakojo Olawale , Abioye Adefunke 
Published: August 2023

Burkholderia is a genus comprising Gram-negative bacteria that are metabolically complex and versatile, thriving in frequently hostile settings. Burkholderia pseudomallei, the causative agent of melioidosis, is a prominent member of the genus and a clinical pathogen of tropical and sub-tropical regions. This pathogen is well known for its multidrug resistance nature and possible bioweapon potential. There is currently no report of the pathogen from clinical specimens in Nigeria, this might be due to misdiagnosis with phenotypic assays. This study aims to explore the accuracy in the use of phenotypic assays to accurately diagnose B. pseudomallei in Nigeria. Two hundred and seventeen (217) clinical samples and twenty-eight (28) Gram-negative clinical isolates were collected and analysed using Ashdown selective agar and monoclonal antibody-based latex agglutination. The species-level identification was achieved using the Analytical profile index (API) 20NE system. The susceptibility of the isolates to nine different antimicrobial agents was determined using the disk diffusion method. Sixty-seven (74) culture-positive isolates were obtained using Ashdown selective agar. Twenty-two isolates were believed to be B. pseudomallei through the monoclonal antibody-based latex agglutination test and API 20NE system subsequently identified 14 isolates as Burkholderia. The predominant Burkholderia species was B. cepacia with isolation rate of 30.8% (8/26). No isolate was distinctively identified as B. pseudomallei but five isolates were highly suspected to be B. pseudomallei with similarity indices ranging from 81.9 – 91.3%. Other bacterial species with definitive identity include Aeromonas sp., Sphingomonas sp. and Pseudomonas aeruginosa. The antibiotic susceptibility results revealed an overall resistance to amoxicillin-clavullanic acid (71.4%), cefepime (33.3%), trimethoprim-sulfamethoxazole (38.1%), piperacillin-tazobactam (33.3%), imipenem (66.7%), doxycycline (57.1%), and ceftazidime (66.7%). The highest intermediate resistance was observed for cefepime and piperacillin-tazobactam with a value 66.7% each while no intermediate-resistance for gentamicin, colistin and imipenem. Our findings, therefore, show that phenotypic assays alone are not enough in the diagnosis of melioidosis. Additionally, it provides a robust basis for supporting present and future decisions to expand diagnostic capability for melioidosis beyond phenotypic assays in low-resource settings.
Mechanisms of Pathogenicity of Hypertrophic Cardiomyopathy-Associated Troponin T (TNNT2) Variant R278C+/-During Development
Authors: Shafaatalab Sanam , Li Alison Y , Jayousi Farah , Maaref Yasaman , Dababneh Saif , Hamledari Homa , Baygi Dina Hosseini , Barszczewski Tiffany , Ruprai Balwinder , Jannati Shayan , Nagalingam Raghu , Cool Austin M , Langa Paulina , Chiao Mu , Roston Thomas , Solaro R John , Sanatani Shubhayan , Toepfer Christopher , Lindert Steffen , Lange Philipp , Tibbits Glen F 
Published: August 2023

AbstractHypertrophic cardiomyopathy (HCM) is one of the most common heritable cardiovascular diseases and variants ofTNNT2(cardiac troponin T) are linked to increased risk of sudden cardiac arrest despite causing limited hypertrophy. In this study, aTNNT2variant, R278C+/-, was generated in both human cardiac recombinant/reconstituted thin filaments (hcRTF) and human-induced pluripotent stem cells (hiPSCs) to investigate the mechanisms by which the R278C+/-variant affects cardiomyocytes at the proteomic and functional levels. The results of proteomics analysis showed a significant upregulation of markers of cardiac hypertrophy and remodeling in R278C+/-vs. the isogenic control. Functional measurements showed that R278C+/-variant enhances the myofilament sensitivity to Ca2+, increases the kinetics of contraction, and causes arrhythmia at frequencies >75 bpm. This study uniquely shows the profound impact of theTNNT2R278C+/-variant on the cardiomyocyte proteomic profile, cardiac electrical and contractile function in the early stages of cardiac development.Translational PerspectiveHypertrophic cardiomyopathy (HCM) is the leading known cause of sudden cardiac arrest in the young. Thin-variant associated HCM variants make up to 15% of familial HCM yet their molecular mechanisms remain less clear relative to thick filament variants. Here, we employ computational modeling, human cardiac recombinant/reconstituted thin filaments (hcRTF), and hiPSC-CMs to study the thin filamentTNNT2R278C+/-variant, revealing its extensive pathogenicity and potential mechanisms by which it can lead to HCM and sudden death. Mavacamten, the recently FDA-approved treatment, was effective in alleviating contractile dysfunction inTNNT2R278C+/-hiPSC-CMs, positing it as a potential therapy for thin filament HCM.Graphical Abstract
Detection of Neuron-Derived cfDNA in Blood Plasma: A New Diagnostic Approach for Neurodegenerative Conditions
Authors: Pollard Chad A. , Aston Kenneth , Emery Benjamin R. , Hill Jonathon , Jenkins Timothy 
Published: August 2023

AbstractNeurodegenerative diseases, such as Alzheimer’s disease (AD), pose significant challenges in early diagnosis, leading to irreversible brain damage and cognitive decline. In this study, we present a novel diagnostic approach that utilizes whole molecule analysis of neuron-derived cell-free DNA (cfDNA) as a biomarker for early detection of neurodegenerative diseases. By analyzing Differential Methylation Regions (DMRs) between purified cortical neurons and blood plasma samples, we identified robust biomarkers that accurately distinguish between neuronal and non-neuronal cfDNA. The use of cfDNA offers the advantage of convenient and minimally invasive sample collection compared to traditional cerebrospinal fluid or tissue biopsies, making this approach more accessible and patient friendly. Targeted sequencing at the identified DMR locus demonstrated that a conservative cutoff of 5% of neuron-derived cfDNA in blood plasma accurately identifies 100% of patients diagnosed with AD, showing promising potential for early disease detection. Additionally, this method effectively differentiated between patients with mild cognitive impairment (MCI) who later progressed to AD and those who did not, highlighting its prognostic capabilities. Importantly, the differentiation between patients with neurodegenerative diseases and healthy controls demonstrated the specificity of our approach. Furthermore, this cfDNA-based diagnostic strategy outperforms recently developed protein-based assays, which often lack accuracy and convenience. While our current approach focused on a limited set of loci, future research should explore the development of a more comprehensive model incorporating multiple loci to increase diagnostic accuracy further. Although certain limitations, such as technical variance associated with PCR amplification and bisulfite conversion, need to be addressed, this study emphasizes the potential of cfDNA analysis as a valuable tool for pre-symptomatic detection and monitoring of neurodegenerative diseases. With further development and validation, this innovative diagnostic strategy has the potential to significantly impact the field of neurodegenerative disease research and patient care, offering a promising avenue for early intervention and personalized therapeutic approaches.
Integration of population-level data sources into an individual-level clinical prediction model for dengue virus test positivity
Authors: Williams RJ , Brintz Ben J. , Dos Santos Gabriel Ribeiro , Huang Angkana , Buddhari Darunee , Kaewhiran Surachai , Iamsirithaworn Sopon , Rothman Alan L. , Thomas Stephen , Farmer Aaron , Fernandez Stefan , Cummings Derek A T , Anderson Kathryn B , Salje Henrik , Leung Daniel T. 
Published: August 2023

AbstractThe differentiation of dengue virus (DENV) infection, a major cause of acute febrile illness in tropical regions, from other etiologies, may help prioritize laboratory testing and limit the inappropriate use of antibiotics. While traditional clinical prediction models focus on individual patient-level parameters, we hypothesize that for infectious diseases, population-level data sources may improve predictive ability. To create a clinical prediction model that integrates patient-extrinsic data for identifying DENV among febrile patients presenting to a hospital in Thailand, we fit random forest classifiers combining clinical data with climate and population-level epidemiologic data. In cross validation, compared to a parsimonious model with the top clinical predictors, a model with the addition of climate data, reconstructed susceptibility estimates, force of infection estimates, and a recent case clustering metric, significantly improved model performance.
Age-dependent effects of adiposity on asthma risk during childhood and adulthood: a lifecourse Mendelian randomization study
Authors: Urquijo Helena , Leyden Genevieve M , Davey Smith George , Richardson Tom G 
Published: August 2023

AbstractBackgroundSeparating the direct and long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse.MethodsIn this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n=13,962 cases) and adult-onset asthma (n=26,582 cases) with a common set of controls (n=300,671) using a technique known as lifecourse Mendelian randomization.FindingsWe found that childhood adiposity increases risk of pediatric asthma (OR=1.20, 95% CI=1.03 to 1.37, P=0.03), whereas there was weak evidence that it has a long-term influence on adult-onset asthma (OR=1.05, 95% CI=0.93 to 1.17, P=0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife using our lifecourse approach (OR=1.37, 95% CI=1.28 to 1.46, P=7×10−12).InterpretationThese findings suggest that adiposity in childhood and adulthood are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse. This inference would not be possible without the application of human genetic data, emphasizing the value of this approach in uncovering risk factors that begin to exert their influence on disease at early stages in life.FundingThe Medical Research Council and the British Heart Foundation.
Metabolomics Identifies and Validates Serum Androstenedione as Novel Biomarker for Diagnosing Primary Angle Closure Glaucoma and Predicting the Visual Field Progression
Authors: Li Shengjie , Ren Jun , Qiu Yichao , Jiang Zhendong , Shao Mingxi , Li Yingzhu , Wu Jianing , Song Yunxiao , Sun Xinghuai , Gao Shunxiang , Cao Wenjun 
Published: August 2023

AbstractBackgroundPrimary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. we aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG.MethodsHere, we used a 5-phases (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui central hospital), cross-sectional, prospective cohort study design to perform widely-targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-Nearest neighbor, and Gaussian NB) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots.ResultsStudied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, areas under the receiver operating characteristic curve [AUC] =1.0 [95%CI, 1.00-1.00]; discovery set, AUC=0.85 [95%CI, 0.80-0.90]) and validation phases (internal validation, AUC=0.86 [95%CI, 0.81-0.91]; external validation, AUC=0.87 [95%CI, 0.80-0.95]).Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, P=0.038) and significantly (P=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio=2.71 [95% CI: 1.199-6.104], P=0.017) were associated with faster visual field progression.ConclusionOur study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression.