bluuebunny/crossref_metadata_2025_split huggingface dataset:
Octamer-binding transcription factor 4-positive circulating tumor cell predicts worse treatment response and survival in advanced cholangiocarcinoma patients who receive immune checkpoint inhibitors treatment
Authors: Pei Fei , Tao Zhen , Lu Qi , Fang Tao , Peng Shasha 
Published: April 2024

Abstract
Background
Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4+CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4+CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment.

Methods
In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4−CTC, and OCT4+CTC groups. Patients were followed up for a median of 10.4 months.

Results
The percentages of patients in none CTC, OCT4−CTC, and OCT4+CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4+CTC group, followed by none CTC group, and lowest in OCT4−CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4+CTC group, moderate in OCT4−CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4+CTC group than in none CTC & OCT4−CTC group. Moreover, OCT4+CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients.

Conclusion
OCT4+CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment.
xWAS analysis in neuropsychiatric disorders by integrating multi-molecular phenotype quantitative trait loci and GWAS summary data
Authors: Luo Lingxue , Pang Tao , Zheng Haohao , Liufu Chao , Chang Suhua 
Published: April 2024

Abstract
Background
Integrating quantitative trait loci (QTL) data related to molecular phenotypes with genome-wide association study (GWAS) data is an important post-GWAS strategic approach employed to identify disease-associated molecular features. Various types of molecular phenotypes have been investigated in neuropsychiatric disorders. However, these findings pertaining to distinct molecular features are often independent of each other, posing challenges for having an overview of the mapped genes.

Methods
In this study, we comprehensively summarized published analyses focusing on four types of risk-related molecular features (gene expression, splicing transcriptome, protein abundance, and DNA methylation) across five common neuropsychiatric disorders. Subsequently, we conducted supplementary analyses with the latest GWAS dataset and corresponding deficient molecular phenotypes using Functional Summary-based Imputation (FUSION) and summary data-based Mendelian randomization (SMR). Based on the curated and supplemented results, novel reliable genes and their functions were explored.

Results
Our findings revealed that eQTL exhibited superior ability in prioritizing risk genes compared to the other QTL, followed by sQTL. Approximately half of the genes associated with splicing transcriptome, protein abundance, and DNA methylation were successfully replicated by eQTL-associated genes across all five disorders. Furthermore, we identified 436 novel reliable genes, which enriched in pathways related with neurotransmitter transportation such as synaptic, dendrite, vesicles, axon along with correlations with other neuropsychiatric disorders. Finally, we identified ten multiple molecular involved regulation patterns (MMRP), which may provide valuable insights into understanding the contribution of molecular regulation network targeting these disease-associated genes.

Conclusions
The analyses prioritized novel and reliable gene sets related with five molecular features based on published and supplementary results for five common neuropsychiatric disorders, which were missed in the original GWAS analysis. Besides, the involved MMRP behind these genes could be given priority for further investigation to elucidate the pathogenic molecular mechanisms underlying neuropsychiatric disorders in future studies.
A PCR-independent approach for mtDNA enrichment and next-generation sequencing: comprehensive evaluation and clinical application
Authors: Liang Dong , Zhu Lin , Zhu Yuqing , Huang Mingtao , Lin Ying , Li Hang , Hu Ping , Zhang Jun , Shen Bin , Xu Zhengfeng 
Published: April 2024

Abstract
Background
Sequencing the mitochondrial genome has been increasingly important for the investigation of primary mitochondrial diseases (PMD) and mitochondrial genetics. To overcome the limitations originating from PCR-based mtDNA enrichment, we set out to develop and evaluate a PCR-independent approach in this study, named Pime-Seq (PCR-independent mtDNA enrichment and next generation Sequencing).

Results
By using the optimized mtDNA enrichment procedure, the mtDNA reads ratio reached 88.0 ± 7.9% in the sequencing library when applied on human PBMC samples. We found the variants called by Pime-Seq were highly consistent among technical repeats. To evaluate the accuracy and reliability of this method, we compared Pime-Seq with lrPCR based NGS by performing both methods simultaneously on 45 samples, yielding 1677 concordant variants, as well as 146 discordant variants with low-level heteroplasmic fraction, in which Pime-Seq showed higher reliability. Furthermore, we applied Pime-Seq on 4 samples of PMD patients retrospectively, and successfully detected all the pathogenic mtDNA variants. In addition, we performed a prospective study on 192 apparently healthy pregnant women during prenatal screening, in which Pime-Seq identified pathogenic mtDNA variants in 4 samples, providing extra information for better health monitoring in these cases.

Conclusions
Pime-Seq can obtain highly enriched mtDNA in a PCR-independent manner for high quality and reliable mtDNA deep-sequencing, which provides us an effective and promising tool for detecting mtDNA variants for both clinical and research purposes.
Antiviral screening of natural, anti-inflammatory compound library against African swine fever virus
Authors: Jackman Joshua A. , Hakobyan Astghik , Grigoryan Rafayela , Izmailyan Roza , Elrod Charles C. , Zakaryan Hovakim 
Published: April 2024

Abstract
Background
African swine fever virus (ASFV) is a major threat to pig production and the lack of effective vaccines underscores the need to develop robust antiviral countermeasures. Pathologically, a significant elevation in pro-inflammatory cytokine production is associated with ASFV infection in pigs and there is high interest in identifying dual-acting natural compounds that exhibit antiviral and anti-inflammatory activities.

Methods
Using the laboratory-adapted ASFV BA71V strain, we screened a library of 297 natural, anti-inflammatory compounds to identify promising candidates that protected Vero cells against virus-induced cytopathic effect (CPE). Virus yield reduction, virucidal, and cell cytotoxicity experiments were performed on positive hits and two lead compounds were further characterized in dose-dependent assays along with time-of-addition, time-of-removal, virus entry, and viral protein synthesis assays. The antiviral effects of the two lead compounds on mitigating virulent ASFV infection in porcine macrophages (PAMs) were also tested using similar methods, and the ability to inhibit pro-inflammatory cytokine production during virulent ASFV infection was assessed by enzyme-linked immunosorbent assay (ELISA).

Results
The screen identified five compounds that inhibited ASFV-induced CPE by greater than 50% and virus yield reduction experiments showed that two of these compounds, tetrandrine and berbamine, exhibited particularly high levels of anti-ASFV activity. Mechanistic analysis confirmed that both compounds potently inhibited early stages of ASFV infection and that the compounds also inhibited infection of PAMs by the virulent ASFV Arm/07 isolate. Importantly, during ASFV infection in PAM cells, both compounds markedly reduced the production of pro-inflammatory cytokines involved in disease pathogenesis while tetrandrine had a greater and more sustained anti-inflammatory effect than berbamine.

Conclusions
Together, these findings support that dual-acting natural compounds with antiviral and anti-inflammatory properties hold promise as preventative and therapeutic agents to combat ASFV infection by simultaneously inhibiting viral replication and reducing virus-induced cytokine production.
Harnessing the potential of African youth for transforming health research in Africa
Authors: Adebisi Yusuff Adebayo , Jimoh Nafisat Dasola , Bassey Archibong Edem , Alaka Hassan Olayemi , Marah Mohamed , Ngoma Chimwemwe , Ogunkola Isaac Olushola , Bouaddi Oumnia , Courage Idahor , Abdelatif El-Abasiri Radwa Abdalla , Boutahar Rime , Ogbodum Molly Unoh , Ekpenyong Aniekan Michael , Uwizeyimana Theogene , Oghenerukevwe Oviri Edith , Olawade David Bamidele 
Published: April 2024

AbstractAfrica faces a significant burden of infectious diseases, including Malaria and HIV/AIDS, along with an increasing prevalence of non-infectious diseases such as diabetes and cancer. This dual health challenge is amplified by socioeconomic difficulties, restricted access to healthcare, and lifestyle changes, thus present unique scientific needs. Effectively addressing these issues requires a skilled scientific workforce adept in comprehensive healthcare strategies. This analysis explores the critical landscape of health research in Africa, emphasizing the unique opportunity presented by the continent’s youthful population, projected to reach almost 1 billion by 2050. The youth’s innovative potential and fresh perspectives offer a chance to overcome development barriers in health research. Nevertheless, challenges such as under-resourced education, limited research training, inadequate mentorship, and funding difficulties persist. This paper urgently calls upon African leaders, international partners, and stakeholders to prioritize health research, mobilize funding, forge strategic partnerships, and empower the youth as essential steps to capitalize on the continent’s dynamic youth for breakthrough health outcomes. Such investments are vital not just for health but for the overall economic, social, and strategic growth of the continent. Through shared responsibility and a united effort, the potential of African youth can be harnessed, leading to transformative research, improved health outcomes, and a prosperous future. This perspective represents the collective voice of passionate young researchers and advocates across Africa, calling for a new era of health research on the continent.
Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis
Authors: Xu Shanshan , Qiu Lixia , Xu Liang , Liu Yali , Zhang Jing 
Published: April 2024

Abstract
Background
Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use.

Method
Risk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis.

Results
During the median follow-up period of 61.00 (57.00–66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02–1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10–5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86–1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01–1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram’s 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80–0.88), 0.83 (95% CI 0.79–0.87), and 0.81 (95% CI 0.77–0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05).

Conclusions
Older age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.
The effect of COVID-19 on the non-COVID health outcomes of crisis-affected peoples: a systematic review
Authors: Thompson N. , Kyaw K. W. Y. , Singh L. , Cikomola J. C. , Singh N. S. , Roberts Bayard 
Published: April 2024

Abstract
Background
The COVID-19 pandemic posed considerable risks to populations affected by humanitarian crises in low- and middle-income countries (LMICs). However, there is limited understanding of how the pandemic may have affected non-COVID health outcomes among crisis-affected populations. Our aim was to examine the evidence on the impact of the COVID-19 pandemic on non-COVID-19 health outcomes for crisis-affected populations in LMICs.

Methods
A systematic review methodology was applied following PRISMA guidelines. Eligibility criteria were: crisis-affected populations in LMICS; COVID-19; and all health topics, except for sexual and reproductive health which was covered in a linked review. Five bibliographic databases and additional grey literature sources were searched. The search period was from 2019 to 31 July 2022. Eligible papers were extracted and analysed using a narrative synthesis approach based on the study objectives and relevant health access and systems frameworks. A quality appraisal was also conducted.

Findings
4320 articles were screened, and 15 eligible studies were identified and included in this review. Ten studies collected health outcomes data. Eight related to mental health, which generally showed worse mental health outcomes because of the pandemic, and pandemic-related stressors were identified. Two studies assessed physical health outcomes in children, while none addressed physical health outcomes among adults. Nine studies reported on access to healthcare, revealing worse access levels due to the pandemic and noting key barriers to care. Seven studies reported on the impact on health systems, with key challenges including reduced and distorted health care funding, reduced staff capacity, interrupted medicines and supplies, weak information and mixed-messaging, and weak leadership. All fifteen studies on the social determinants of health, particularly highlighting the effect of increasing poverty, the role of gender, and food insecurity on health outcomes. The quality of papers was limited overall.

Conclusion
This review found some limited evidence indicating negative mental health effects, increased barriers to accessing care, damage to health systems and magnified impacts on the social determinants of health for crisis-affected people during the COVID-19 pandemic. However, the small number and limited quality of the studies make the overall strength of evidence quite weak.
Centrifuger: lossless compression of microbial genomes for efficient and accurate metagenomic sequence classification
Authors: Song Li , Langmead Ben 
Published: April 2024

AbstractCentrifuger is an efficient taxonomic classification method that compares sequencing reads against a microbial genome database. In Centrifuger, the Burrows-Wheeler transformed genome sequences are losslessly compressed using a novel scheme called run-block compression. Run-block compression achieves sublinear space complexity and is effective at compressing diverse microbial databases like RefSeq while supporting fast rank queries. Combining this compression method with other strategies for compacting the Ferragina-Manzini (FM) index, Centrifuger reduces the memory footprint by half compared to other FM-index-based approaches. Furthermore, the lossless compression and the unconstrained match length help Centrifuger achieve greater accuracy than competing methods at lower taxonomic levels.
Thyroid hormone induces ossification and terminal maturation in a preserved OA cartilage biomimetic model
Authors: Korthagen N. M. , Houtman E. , Boone I. , Coutinho de Almeida R. , Sivasubramaniyan K. , Mahdad R. , Nelissen R. G. H. H , Ramos Y. F. M. , Tessari M. A , Meulenbelt I. 
Published: April 2024

Abstract
Objective
To characterize aspects of triiodothyronine (T3) induced chondrocyte terminal maturation within the molecular osteoarthritis pathophysiology using the previously established T3 human ex vivo osteochondral explant model.

Designs
RNA-sequencing was performed on explant cartilage obtained from OA patients (n = 8), that was cultured ex vivo with or without T3 (10 ng/ml), and main findings were validated using RT-qPCR in an independent sample set (n = 22). Enrichment analysis was used for functional clustering and comparisons with available OA patient RNA-sequencing and GWAS datasets were used to establish relevance for OA pathophysiology by linking to OA patient genomic profiles.

Results
Besides the upregulation of known hypertrophic genes EPAS1 and ANKH, T3 treatment resulted in differential expression of 247 genes with main pathways linked to extracellular matrix and ossification. CCDC80, CDON, ANKH and ATOH8 were among the genes found to consistently mark early, ongoing and terminal maturational OA processes in patients. Furthermore, among the 37 OA risk genes that were significantly affected in cartilage by T3 were COL12A1, TNC, SPARC and PAPPA.

Conclusions
RNA-sequencing results show that metabolic activation and recuperation of growth plate morphology are induced by T3 in OA chondrocytes, indicating terminal maturation is accelerated. The molecular mechanisms involved in hypertrophy were linked to all stages of OA pathophysiology and will be used to validate disease models for drug testing.
Optic neuritis and mydriasis after vaccination: a case report
Authors: Bonamigo Elcio Luiz , Kuyava Pamela , Reginatto Taísa Sacomori Paula Zanotto , Duran Arthur Gabriel , Truculo Luisa , Rossi Eglas Emanuel , Stock Ricardo Alexandre , Grasel Claudia Elisa 
Published: April 2024

Abstract
Background
Optic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve, with various causes. Its incidence is higher in children and young adults than in older adults of both genders, but is more common in women than in men. ON is rarely associated with mydriasis, and it is seldom triggered by vaccines against tetanus and diphtheria.

Case report
A 36-year-old Caucasian woman presented with bilateral ON that had started 18 days after administration of a booster dose of the double adult vaccine (dT) against diphtheria and tetanus. Bilateral mydriasis persisted after treatment and clinical resolution of the ON. She experienced severe headache, blurred vision, decreased visual acuity in the right eye and bilateral mydriasis, a diagnosis confirmed by imaging tests. Treatment with oral corticosteroids resulted in rapid resolution of the neuritis; however, mydriasis persisted for several months.

Conclusion
This study describes a very unusual case of bilateral ON associated with prolonged mydriasis after vaccination against tetanus and diphtheria that regressed after treatment with oral corticosteroids. Prolonged mydriasis was the manifestation that differed from the other cases previously described.
Recurrent ventilator-associated pneumonia in severe Covid-19 ARDS patients requiring ECMO support
Authors: Collado-Lledó Elena , Moyon Quentin , Chommeloux Juliette , Pineton de Chambrun Marc , Hékimian Guillaume , Saura Ouriel , Lévy David , Schmidt Matthieu , Combes Alain , Luyt Charles-Edouard , Le Fevre Lucie 
Published: April 2024

Abstract
Objective
To describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence.

Methods
Adult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence.

Results
Among the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7–13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [< 8 days, median (IQR) duration 6 (5–7) days] and 52 (25%) received a prolonged course of antibiotics [≥ 8 days, median (IQR) duration 9 (8–10) days]. Estimated cumulative incidence of VAP recurrence, taking into account death and extubation as competing risks, was not different in patients with short– and prolonged–antimicrobial treatment.

Conclusions
In patients with severe Covid-19–ARDS requiring ECMO support, VAP recurrence occurs frequently, with Enterobacteriaceae and Pseudomonas aeruginosa as predominant causative microorganisms. An antimicrobial treatment of ≥ 8 days for the treatment of first VAP episode did not reduce the risk of VAP recurrence, as compared to shorter duration.
Psychometric properties of the Spanish version of the functionality appreciation scale
Authors: Zamora Ángel , Desdentado Lorena , Herrero Rocío , Miragall Marta , Baños Rosa 
Published: April 2024

Abstract
Background
The Functionality Appreciation Scale is a 7-item measure of an individual’s appreciation of his or her body for what it can do and is capable of doing. While this instrument has been increasingly used in intervention-based research, its psychometric properties have not been extensively studied in non-English-speaking populations. The psychometric properties of a novel Spanish translation of the FAS were examined.

Methods
An online sample of 838 Spanish adults (mean age = 31.79 ± 11.95 years, 50.48% men) completed the Spanish FAS and validated measures of body appreciation, eating disorder symptomatology, intuitive eating, and life satisfaction.

Results
Exploratory factor analysis supported a 1-dimensional factor structure of the FAS, which was further supported by confirmatory factor analysis (SBχ²(14) = 83.82, SBχ²normed = 1.48, robust RMSEA = 0.094 (90% CI = 0.074, 0.115), SRMR = 0.040, robust CFI = 0.946, robust TLI = 0.924). Invariance across genders was shown, and there were no significant differences according to gender (t(417) = 0.77, p =.444, d = 0.07). Construct validity was also supported through significant associations with the other measures of the study. Incremental validity was established in women. Thus, appreciation of functionality predicted life satisfaction over and above the variance accounted for by other body image and eating disorder-related measures (F(4, 399) = 18.86, p <.001, ΔR2 = 0.03).

Conclusions
These results support the psychometric properties of the Spanish FAS and demonstrate the importance of the appreciation of functionality in relation to a healthier body image and psychological wellbeing.