bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased neutrophil extracellular trap formation in oligoarticular, polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis: biomarkers for diagnosis and disease activity
Authors: Tang Hongxia , Zhong Yucheng , Wu Yali , Huang Yanmei , Liu Yi , Chen Jing , Xi Ting , Wen Yini , He Ting , Yang Shanshan , Liu Fan , Xiong Runji , Jin Runming 
Published: August 2024

ObjectiveNeutrophil extracellular traps (NETs) are important factors in initiating and perpetuating inflammation. However, the role of NETs in different subtypes of juvenile idiopathic arthritis (JIA) has been rarely studied. Therefore, we aimed to explore the ability of JIA-derived neutrophils to release NETs and the effect of TNF-α (tumor necrosis factor-alpha) inhibitors on NET formation both in vitro and in vivo, and evaluate the associations of NET-derived products with clinical and immune-related parameters.MethodsThe ability of neutrophils to release NETs and the effect of adalimumab on NET formation was assessed via in vitro stimulation and inhibition studies. Plasma NET-derived products were detected to assess the incidence of NET formation in vivo. Furthermore, flow cytometry and western blotting were used to detect NET-associated signaling components in neutrophils.ResultsCompared to those derived from HCs, neutrophils derived from patients with oligoarticular-JIA, polyarticular-JIA and enthesitis-related arthritis were more prone to generate NETs spontaneously and in response to TNF-α or PMA in vitro. Excessive NET formation existed in peripheral circulation of JIA patients, and elevated plasma levels of NET-derived products (cell-free DNA and MPO-DNA complexes) could accurately distinguish JIA patients from HCs and were positively correlated with disease activity. Multiple linear regression analysis showed that erythrocyte sedimentation rate and TNF-α levels were independent variables and were positively correlated with cell-free DNA concentration. Notably, TNF-α inhibitors could effectively prevent NET formation both in vitro and in vivo. Moreover, the phosphorylation levels of NET-associated kinases in JIA-derived neutrophils were markedly increased.ConclusionOur data suggest that NETs might play pathogenic roles and may be involved in TNF-α-mediated inflammation in JIA. Circulating NET-derived products possess potential diagnostic and disease monitoring value. Furthermore, the preliminary results related to the molecular mechanisms of NET formation in JIA patients provide a theoretical basis for NET-targeted therapy.
Investigating the impact of STING pathway activation on breast cancer treatment outcomes: development and validation of a prognostic model
Authors: Zhong YangYan , Cao Hong , Li Wei , Deng Jian , Li Dan , Deng JunJie 
Published: August 2024

IntroductionBreast cancer (BRCA) is a significant cause of cancer-associated mortality across the globe. Current therapeutic approaches face challenges such as drug resistance and metastasis. Immune signaling is triggered by chromosomal instability (CIN) generates misplaced DNA structures that activate the cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, triggering. Studies have linked STING activation to BRCA treatment.MethodsThe bulk RNA-seq data for patients with BRCA were collected from the TCGA-BRCA cohort, GSE20685, and GSE96058 cohorts. STING pathway-related genes (SRGs) were obtained from the Reactome database. Differentially expressed genes were analyzed using the limma package. Immune cell infiltration was analyzed using the IOBR package. Gene Ontology biological processes, Kyoto Encyclopedia of Genes and Genomes pathways, and cancer hallmark pathways were analyzed using the MSigDB database. Prognostic models were prepared using the least absolute shrinkage and selection operator and multiple-factor Cox regression analysis. Single-cell analysis was performed using the Seurat and SCP pipeline.ResultsThe expression patterns and clinical relevance of SRGs were analyzed in patients with BRCA. Transcriptional differences in the SRGs were observed between normal and tumorous tissues, with global down-regulated STING1 and up-regulated TBK1 in BRCA tissue. Tumor tissues were classified through consensus clustering analysis into two distinct groups, with differences in clinical characteristics and immune infiltration. A prognostic model related to the differences in STING pathway activity—high prognostic stratification potency—was developed and validated. Correlation analysis revealed suppressed overall immune activation in patients with BRCA having higher risk scores. Gemcitabine had a more favorable outcome in the low-risk group. The activity of the prognostic model at the single-cell level was confirmed through single-cell analysis, particularly in CD8 T cells and intratumor natural killer cells.ConclusionA STING pathway-related prognostic model developed and validated and the model could accurately predict BRCA patient outcomes. These findings have important implications for the personalized treatment and management of patients with BRCA.
Strengthening surgical healthcare research capacity in sub-Saharan Africa: impact of a research training programme in Nigeria
Authors: Ameh Emmanuel A. , Seyi-Olajide Justina O. , Ameh Nkeiruka , Michael Afieharo , Abdullahi Mohammed AS , Aria Oti Nimi , Obi Nkeiruka , Chukwu Isaac 
Published: August 2024

BackgroundLimited research capacity has contributed to the lack of high-quality research from low-and middle-income countries. This is compounded by limited research training opportunities. Research capacity scale-up training was deployed as part of the implementation of the National Surgical, Obstetrics, Anaesthesia, and Nursing Plan for Nigeria. We report the impact of this locally contextualized efforts to scale up research capacity in sub-Saharan Africa.MethodsThis is an evaluation of the training of 65 participants in research, grant writing and manuscript writing and publication. Pre- and post-training surveys using a 5-point Likert scale and open-ended questions were administered to evaluate the impact of the programme.ResultsThere were 39 (60%) males and 26 (40%) females aged 26–62 years (median 42 years). Thirty-nine (60%) participants had previous training in research, but only 12 (18.5%) had previously received grant writing training, and 17 (26.2%) had previously received manuscript writing and publishing training. Following training, 45 (70.3%) participants agreed that the training was relevant. The research, grant writing and manuscript writing, and publication components of the training were rated high by the participants (45–59, 70.3–92.2%). However, 41.2% felt that there was not enough time, and 32.4% felt that the training was too comprehensive. Nearly all the participants agreed that the training had improved their skills in research, grant writing and manuscript writing and publication, and more than two-thirds subsequently engaged in informal mentoring of others. Overall, participants achieved success in designing their own research projects and publishing manuscripts and grants. Three (4.6%) of the participants had gone on to become faculty for the research training programme. The three top barriers encountered following training were time constraints (67.3%), lack of funding (36.5%) and not being able to find research collaborators (25%).ConclusionOutcome of this training programme is encouraging and highlights the feasibility and potential impact of deploying such programmes in low and middle income countries (LMICs). Despite the positive outcomes, barriers including time constraints, funding limitations, and difficulties in finding research collaborators remain to be addressed. Such training programmes need to be supported to strengthen the research capacity in this and similar settings.
In-utero exposure to tenofovir disoproxil fumarate pre-exposure prophylaxis and growth metrics in HIV unexposed breastfed infants in South Africa: a post hoc analysis of the CAP 016 PrEP in pregnancy RCT
Authors: Naidoo Megeshinee , Naidoo Kimesh L. , Lombard Carl , Desmond Alicia C. , Clark Richard , Rooney James F. , Gray Glenda , Moodley Dhayendre 
Published: August 2024

ObjectiveWe evaluated growth metrics in HIV unexposed African breastfed infants in the first 18 months of life in association with in-utero exposure to Tenofovir Diphosphate Fumarate (TDF) containing pre-exposure prophylaxis (PrEP).DesignWe conducted a secondary data analysis of a TDF-PrEP randomized control trial (CAP016 RCT). Pregnant women without HIV were randomized to initiating TDF-PrEP in pregnancy (Immediate-PrEP-IP) or deferred initiation of TDF-PrEP at cessation of breastfeeding (Deferred-PrEP-DP).MethodsInfant weight (W), length (L), and head circumference (HC) were measured at birth and 6, 26, 50, and 74 weeks of age. Stored dried blood spot samples from pregnant women randomized to the IP arm were used to measure tenofovir-diphosphate (TFV-DP) levels. Age-stratified mean weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), and head circumference-for-age (HCAZ) Z-scores were compared between infants exposed to varying TFV-DP concentrations and infants in the DP arm.ResultsA total of 455 mother-infant pairs were included in the secondary analysis, 228 in the IP arm and 227 in the DP arm. WAZ, LAZ, WLZ, and HCAZ scores were comparable between infants in the Deferred-PrEP arm and Immediate-PrEP arm. In a mixed-effects linear regression model adjusting for maternal age, body mass index, socioeconomic and newborn characteristics, in-utero exposure to varying TFV-DP levels was not associated with WAZ (β = −0.52), LAZ (β = −0.46), WLZ (β = −0.43) and HCAZ (β = −0.11) scores over time.ConclusionThere was no evidence of an association between growth metrics in the first 18 months of life and in-utero exposure to TFV-DP among breastfed HIV unexposed infants.
Safety, effectiveness, and usefulness of higher-dose tablets of generic pirfenidone in patients with IPF: a nationwide observational study in South Korea
Authors: Kang Jieun , Lee Kwan Ho , Lee Jae Ha , Jeong Yi Yeong , Choi Sun Mi , Kim Ho Cheol , Park Joo Hun , Lee Hyun-Kyung , Yong Suk Joong , Choi Hye Sook , Kim Hak Ryul , Jegal Yangjin , Choi Won-il , Lee Eun Joo , Song Jin Woo 
Published: August 2024

BackgroundPirfenidone is an antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF). Fybro®, a generic version of pirfenidone developed in South Korea, gained approval and is available in 200 mg and in higher-dose formulations of 400 and 600 mg. This real-world prospective cohort study investigated the safety and effectiveness of Fybro®.MethodsA nationwide observational study was conducted in patients with IPF. Patients were followed up for 6 months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected. Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens were compared.ResultsOf the 359 enrolled patients, 352 received pirfenidone (Fybro®) at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. The median treatment duration was 186.0 days. A total of 253 patients (71.9%) experienced adverse events, with decreased appetite being the most common (16.5%). The adjusted decline rates in lung function were −1.5% and −2.2% predicted per year for forced vital capacity and diffusing capacity, respectively. No significant differences were observed based on the pirfenidone dose. For a daily intake of 1,200 or 1800 mg of pirfenidone, a significantly longer duration of drug administration was observed with the fewer-pill regimen than with multiple-pill regimen.ConclusionThe safety and effectiveness of Fybro® observed in this real-world cohort study are consistent with previous studies. Using higher-strength tablets to reduce pill burden may improve medication adherence.
Complete mitochondrial genome assembly of Zizania latifolia and comparative genome analysis
Authors: Luo Xianyang , Gu Cuicui , Gao Sijia , Li Man , Zhang Haixiang , Zhu Shidong 
Published: August 2024

Zizania latifolia (Griseb.) Turcz. ex Stapf has been cultivated as a popular aquatic vegetable in China due to its important nutritional, medicinal, ecological, and economic values. The complete mitochondrial genome (mitogenome) of Z. latifolia has not been previously studied and reported, which has hindered its molecular systematics and understanding of evolutionary processes. Here, we assembled the complete mitogenome of Z. latifolia and performed a comprehensive analysis including genome organization, repetitive sequences, RNA editing event, intercellular gene transfer, phylogenetic analysis, and comparative mitogenome analysis. The mitogenome of Z. latifolia was estimated to have a circular molecule of 392,219 bp and 58 genes consisting of three rRNA genes, 20 tRNA genes, and 35 protein-coding genes (PCGs). There were 46 and 20 simple sequence repeats (SSRs) with different motifs identified from the mitogenome and chloroplast genome of Z. latifolia, respectively. Furthermore, 49 homologous fragments were observed to transfer from the chloroplast genome to the mitogenome of Z. latifolia, accounting for 47,500 bp, presenting 12.1% of the whole mitogenome. In addition, there were 11 gene-containing homologous regions between the mitogenome and chloroplast genome of Z. latifolia. Also, approximately 85% of fragments from the mitogenome were duplicated in the Z. latifolia nuclear genome. Selection pressure analysis revealed that most of the mitochondrial genes were highly conserved except for ccmFc, ccmFn, matR, rps1, and rps3. A total of 93 RNA editing sites were found in the PCGs of the mitogenome. Z. latifolia and Oryza minuta are the most closely related, as shown by collinear analysis and the phylogenetic analysis. We found that repeat sequences and foreign sequences in the mitogenomes of Oryzoideae plants were associated with genome rearrangements. In general, the availability of the Z. latifolia mitogenome will contribute valuable information to our understanding of the molecular and genomic aspects of Zizania.
Filling the gap: brief neuropsychological assessment protocol for glioma patients undergoing awake surgeries
Authors: Ohy Juliana Bastos , Formentin Cleiton , Gripp Daniel Andrade , Nicácio Jr Joab Alves , Velho Maíra Cristina , Vilany Larissa Núbia , Greggianin Gabriel Frizon , Sartori Beatriz , Campos Ana Carolina Pinheiro , Verst Silvia Mazzali , Maldaun Marcos Vinicius Calfat 
Published: August 2024

IntroductionThe literature lacks a concise neurocognitive test for assessing primary cognitive domains in neuro-oncological patients. This study aims to describe and assess the feasibility of the Ohy-Maldaun Fast Track Cognitive Test (OMFTCT), used to pre- and post-operatively evaluate patients undergoing brain tumor surgery in language eloquent areas. The cognitive diagnosis was used to safely guide intraoperative language assessment.MethodsThis is a prospective longitudinal observational clinical study conducted on a cohort of 50 glioma patients eligible for awake craniotomies. The proposed protocol assesses multiple cognitive domains, including language, short-term verbal and visual memories, working memory, praxis, executive functions, and calculation ability. The protocol comprises 10 different subtests, with a maximum score of 50 points, and was applied at three time points: preoperative, immediately postoperative period, and 30 days after surgery.ResultsAmong the initial 50 patients enrolled, 36 underwent assessment at all three designated time points. The mean age of the patients was 45.3 years, and they presented an average of 15 years of education. The predominant tumor types included Glioblastoma, IDH-wt (44.1%), and diffuse astrocytoma, IDH-mutant (41.2%). The tumors were located in the left temporal lobe (27.8%), followed by the left frontal lobe (25%). The full test had an average application time of 23 min.ConclusionOMFTCT provided pre- and postoperative assessments of different cognitive domains, enabling more accurate planning of intraoperative language testing. Additionally, recognition of post-operative cognitive impairments played a crucial role in optimizing patient care.
Psychiatrists as forensic authorities: evaluation of dangerous habitual offenders in West Germany during the 1960s – the Helmut Hoinka case
Authors: Kosenko Oxana , Skuban-Eiseler Tobias , Steger Florian 
Published: August 2024

BackgroundPreventive detention for highly dangerous habitual offenders has been in force in Germany for 90 years. The necessity of this measure is hotly debated from a legal perspective. However, the assignment of preventive detention is largely determined by the opinion of medical experts. This article discusses the role of medical experts and the issues they face in evaluating the dangerousness of habitual offenders using the case of the marriage swindler Helmut Hoinka, prosecuted several times in the Federal Republic of Germany in the 1960s.MethodsHelmut Hoinka’s case was chosen for analysis because of the rare opportunity to access detailed materials that allowed us to follow in detail the reasoning of the medical experts who evaluated Hoinka: medical reports stored in the Gerd Huber Archive at the University of Ulm, and Hoinka’s court case from the State Archive of North Rhine-Westphalia. To examine these sources, we implemented the historical-critical method.ResultsThe medical experts who evaluated Hoinka were aware of the defendant’s criminal record prior to the evaluation, which was a source of bias. In addition, the criteria for classifying the offender as a dangerous habitual offender were open to a wide range of interpretations. Hoinka’s high level of intelligence was negatively emphasized. Some test results were considered unreliable because it was assumed that Hoinka had manipulated his answers. Personal value judgments were allowed in assessing Hoinka’s personality. Hoinka’s criminal behavior was considered a medical symptom of psychopathy because it violated general moral and social norms. The medical reports of both experts showed that the psychiatrists believed in the genetic nature of psychopathy and criminal behavior. Their criminological prognosis was fully supported by the court in imposing the sentence.ConclusionChallenges to Hoinka’s criminological prognosis were the experts’ personal biases, their belief in the theory of genetic predisposition to crime, the lack of clear criteria for antisocial personality disorder, and the absence of forensic recommendations for “psychopathic” criminals. The experts’ opinion on Hoinka’s criminal predisposition was crucial to the imposition of the sentence.
A randomized controlled add-on trial of fluoxetine and cognitive behavioral therapy for help-seeking men with a sexual interest in children: presentation of the PARACHUTES trial protocol and initial feasibility data
Authors: Adebahr Roberth , Görts Öberg Katarina , Rahm Christoffer , Byström Markus , Sparre Charlotte , Desai Boström Adrian E. , Bottai Matteo , Jokinen Jussi , Savard Josephine 
Published: August 2024

BackgroundSexual Interest in Children (SIC) is a major risk factor for sexual offending, yet clinical trials are sparse. The present protocol outlines a randomized controlled trial (RCT) that aims to investigate the effectiveness of fluoxetine and Cognitive Behavioral Therapy (CBT) in help-seeking men with SIC.MethodsAdult men contacting the Swedish telephone helpline PrevenTell are screened for inclusion and invited to further assessment on site. One hundred and eleven men with SIC (defined as DSM-5 pedophilic disorder or hebephilia) will be randomized (1:1:1 ratio) to receive one of three interventions for 14 weeks: (1) an internet-administered psychoeducational program (iPP), (2) iPP and the addition of fluoxetine 20-40 mg or (3) iPP and the addition of internet-administered CBT (iCBT). Exclusion criteria include severe psychiatric illness, contraindicating treatment and an elevated risk of committing hands-on sexual offences. Symptom intensity is assessed at baseline, pre-treatment, every other week for 12 weeks, and post treatment. The primary outcome measure is the Sexual Interest in Children: Current Assessment Scale (SIC: CAS) that quantifies sexual behaviors associated with SIC as well as perceived distress and impairment. Secondary outcomes include measures of dynamic risk-factors for committing sexual offences.ResultsThe data collected during the initial 20 months of recruitment were analyzed to predict the required number of individuals to be screened and estimate the probable length of the data collection phase. As of March 2022 to November 2023, 146 men have called PrevenTell and disclosed a sexual interest in minors. Following pre-screening, 110 men were excluded from participation in the trial. Current SSRI therapy was the primary reason for exclusion (n = 24; 22%), followed by an elevated risk of committing hands-on sexual offences (n = 14; 13%). Among the 31 men who underwent the screening procedure on site, 26 were allocated to either iPP, iPP+fluoxetine, or iPP+iCBT. The recruitment rate indicates that the trial will be concluded within the pre-estimated timeframe.DiscussionThis is the first RCT of treatment with SSRI and iCBT in a population of help-seeking men with SIC. The significance of this trial and its methodological strengths and limitations are discussed.