bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol of the HD-MED study aiming to personalize drug treatment in Huntington’s disease: a longitudinal, observational study to assess medication use and efficacy in relation to pharmacogenetics
Authors: Feleus Stephanie , van der Lee Maaike , Swen Jesse J. , Roos Raymund A. C. , de Bot Susanne T. 
Published: November 2023

Background: Huntington’s disease (HD) is a hereditary, neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Currently, HD can only be managed symptomatically, including a large variety of prescribed drugs. Many HD patients experience negative medication effects (e.g. side effects or non-response). Pharmacogenetic (PGx) studies show how genetic variation affects both medication efficacy and toxicity and holds the potential to improve these outcomes of drug treatment. Primary objective: To classify the effect of the PGx profile of CYP2C19 and CYP2D6 in HD gene expansion carriers on negative medication effects of HD-related medication. Design: Multicenter, observational study with 1-year follow-up. Adult HD gene expansion carriers who use one or more HD-related medications are eligible to participate. Methods and analysis: A detailed overview of medication use, medication efficacy, and side effects is retrospectively and prospectively collected via medication diaries, questionnaires, phone calls, and pharmacy medication verification schemes. PGx analysis on whole blood-extracted DNA is performed with Agena Bioscience VeriDose® Core Panel and long-range polymerase chain reaction copy number variation analysis. Per the study protocol-defined negative medication effects in HD gene expansion carriers with a genotype predicted poor or ultrarapid metabolizer phenotype will be compared with HD gene expansion carriers with a predicted intermediate and normal metabolizer phenotype. Frequencies will be analyzed via χ2 and logistic multivariate regression analysis. In addition, we summarize in this manuscript HD-relevant PGx prescription recommendations to improve drug therapy. Ethics: The original study protocol was approved by the medical research ethics committee Leiden Den Haag Delft on 26 November 2019. Discussion: HD-MED is a low-risk study that will generate personalized PGx results that can immediately be implemented in clinical practice, thus potentially improving pharmacovigilance and patients’ quality of life. Registration: This study is registered in the International Clinical Trial Registry Platform under registration number NL8251, URL https://trialsearch.who.int/Trial2.aspx?TrialID=NL8251 .
Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas: results of a phase 1 trial
Authors: Brudno Jennifer N. , Natrakul Danielle A. , Karrs Jeremiah , Patel Nisha , Maass-Moreno Roberto , Ahlman Mark A. , Mikkilineni Lekha , Mann Jennifer , Stroncek David F. , Highfill Steven L. , Fromm Genevieve C. , Patel Rashmika , Pittaluga Stefania , Kochenderfer James N. 
Published: November 2023

Abstract
New treatments are needed for relapsed and refractory CD30-expressing lymphomas. We developed a novel anti-CD30 chimeric antigen receptor (CAR), designated 5F11-28Z. Safety and feasibility of 5F11-28Z–transduced T cells (5F11-Ts) were evaluated in a phase 1 dose escalation clinical trial. Patients with CD30-expressing lymphomas received 300 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days −5 to −3, followed by infusion of 5F11-Ts on day 0. Twenty-one patients received 5F11-T infusions. Twenty patients had classical Hodgkin lymphoma, and 1 had anaplastic large-cell lymphoma. Patients were heavily pretreated, with a median of 7 prior lines of therapy and substantial tumor burden, with a median metabolic tumor volume of 66.1 mL (range, 6.4-486.7 mL). The overall response rate was 43%; 1 patient achieved a complete remission. Median event-free survival was 13 weeks. Eleven patients had cytokine release syndrome (CRS; 52%). One patient had grade 3 CRS, and there was no grade 4/5 CRS. Neurologic toxicity was minimal. Nine patients (43%) had new-onset rashes. Two patients (9.5%) received extended courses of corticosteroids for prolonged severe rashes. Five patients (24%) had grade 3/4 cytopenias, with recovery time of ≥30 days, and 2 of these patients (9.5%) had prolonged cytopenias with courses complicated by life-threatening sepsis. The trial was halted early because of toxicity. Median peak blood CAR+ cells per μL was 26 (range, 1-513 cells per μL), but no infiltration of CAR+ cells was detected in lymph node biopsies. 5F11-Ts had low efficacy and substantial toxicities, which limit further development of 5F11-Ts. This trial was registered at www.clinicaltrials.gov as #NCT03049449.
Candidate biomarkers for treatment benefit from sunitinib in patients with advanced renal cell carcinoma using mass spectrometry-based (phospho)proteomics
Authors: van der Wijngaart Hanneke , Beekhof Robin , Knol Jaco C. , Henneman Alex A. , de Goeij-de Haas Richard , Piersma Sander R. , Pham Thang V. , Jimenez Connie R. , Verheul Henk M. W. , Labots Mariette 
Published: November 2023

AbstractThe tyrosine kinase inhibitor sunitinib is an effective first-line treatment for patients with advanced renal cell carcinoma (RCC). Hypothesizing that a functional read-out by mass spectrometry-based (phospho, p-)proteomics will identify predictive biomarkers for treatment outcome of sunitinib, tumor tissues of 26 RCC patients were analyzed. Eight patients had primary resistant (RES) and 18 sensitive (SENS) RCC. A 78 phosphosite signature (p < 0.05, fold-change > 2) was identified; 22 p-sites were upregulated in RES (unique in RES: BCAR3, NOP58, EIF4A2, GDI1) and 56 in SENS (35 unique). EIF4A1/EIF4A2 were differentially expressed in RES at the (p-)proteome and, in an independent cohort, transcriptome level. Inferred kinase activity of MAPK3 (p = 0.026) and EGFR (p = 0.045) as determined by INKA was higher in SENS. Posttranslational modifications signature enrichment analysis showed that different p-site-centric signatures were enriched (p < 0.05), of which FGF1 and prolactin pathways in RES and, in SENS, vanadate and thrombin treatment pathways, were most significant. In conclusion, the RCC (phospho)proteome revealed differential p-sites and kinase activities associated with sunitinib resistance and sensitivity. Independent validation is warranted to develop an assay for upfront identification of patients who are intrinsically resistant to sunitinib.
Tacrolimus reverses pemphigus vulgaris serum-induced depletion of desmoglein in HaCaT cells via inhibition of heat shock protein 27 phosphorylation
Authors: Xie Zhimin , Dai Xiangnong , Li Qingqing , Lin Sifan , Ye Xingdong 
Published: November 2023

Abstract
Background
Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has been reported to have an adjuvant treatment effect against PV. However, the mechanism underlying the inhibitory effect of FK506 on PV-IgG-induced acantholysis is unclear.

Objective
The objective of this study was to explore the effect of FK506 on desmoglein (Dsg) expression and cell adhesion in an immortalized human keratinocyte cell line (HaCaT cells) stimulated with PV sera.

Methods
A cell culture model of PV was established by stimulating HaCaT cells with 5% PV sera with or without FK506 and clobetasol propionate (CP) treatment. The effects of PV sera on intercellular junctions and protein levels of p38 mitogen-activated protein kinase (p38MAPK), heat shock protein 27 (HSP27), and Dsg were assayed using western blot analysis, immunofluorescence staining, and a keratinocyte dissociation assay.

Results
PV sera-induced downregulation of Dsg3 was observed in HaCaT cells and was blocked by FK506 and/or CP. Immunofluorescence staining revealed that linear deposits of Dsg3 on the surface of HaCaT cells in the PV sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface; however, this effect was reversed by FK506 and/or CP treatment. Furthermore, cell dissociation assays showed that FK506 alone or in combination with CP increased cell adhesion in HaCaT cells and ameliorated loss of cell adhesion induced by PV sera. Additionally, FK506 noticeably decreased the PV serum-induced phosphorylation of HSP 27, but had no effect on p38MAPK phosphorylation.

Conclusion
FK506 reverses PV-IgG induced-Dsg depletion and desmosomal dissociation in HaCaT cells, and this effect may be obtained by inhibiting HSP27 phosphorylation.
Transcriptomic characterization of Trichoderma harzianum T34 primed tomato plants: assessment of biocontrol agent induced host specific gene expression and plant growth promotion
Authors: Aamir Mohd , Shanmugam V. , Dubey Manish Kumar , Husain Fohad Mabood , Adil Mohd , Ansari Waquar Akhter , Rai Ashutosh , Sah Pankaj 
Published: November 2023

AbstractIn this study, we investigated the intricate interplay between Trichoderma and the tomato genome, focusing on the transcriptional and metabolic changes triggered during the late colonization event. Microarray probe set (GSE76332) was utilized to analyze the gene expression profiles changes of the un-inoculated control (tomato) and Trichoderma-tomato interactions for identification of the differentially expressed significant genes. Based on principal component analysis and R-based correlation, we observed a positive correlation between the two cross-comaparable groups, corroborating the existence of transcriptional responses in the host triggered by Trichoderma priming. The statistically significant genes based on different p-value cut-off scores [(padj-values or q-value); padj-value < 0.05], [(pcal-values); pcal-value < 0.05; pcal < 0.01; pcal < 0.001)] were cross compared. Through cross-comparison, we identified 156 common genes that were consistently significant across all probability thresholds, and showing a strong positive corelation between p-value and q-value in the selected probe sets. We reported TD2, CPT1, pectin synthase, EXT-3 (extensin-3), Lox C, and pyruvate kinase (PK), which exhibited upregulated expression, and Glb1 and nitrate reductase (nii), which demonstrated downregulated expression during Trichoderma-tomato interaction. In addition, microbial priming with Trichoderma resulted into differential expression of transcription factors related to systemic defense and flowering including MYB13, MYB78, ERF2, ERF3, ERF5, ERF-1B, NAC, MADS box, ZF3, ZAT10, A20/AN1, polyol sugar transporter like zinc finger proteins, and a novel plant defensin protein. The potential bottleneck and hub genes involved in this dynamic response were also identified. The protein–protein interaction (PPI) network analysis based on 25 topmost DEGS (pcal-value < 0.05) and the Weighted Correlation Gene Network Analysis (WGCNA) of the 1786 significant DEGs (pcal-value < 0.05) we reported the hits associated with carbohydrate metabolism, secondary metabolite biosynthesis, and the nitrogen metabolism. We conclude that the Trichoderma-induced microbial priming re-programmed the host genome for transcriptional response during the late colonization event and were characterized by metabolic shifting and biochemical changes specific to plant growth and development. The work also highlights the relevance of statistical parameters in understanding the gene regulatory dynamics and complex regulatory networks based on differential expression, co-expression, and protein interaction networks orchestrating the host responses to beneficial microbial interactions.
Clinical characteristics of hospitalized patients with Nocardia genus detection by metagenomic next generation sequencing in a tertiary hospital from southern China
Authors: Liang Yingjian , Lin Minmin , Qiu Lidi , Chen Meizhu , Tan Cuiyan , Tu Changli , Zheng Xiaobin , Liu Jing 
Published: November 2023

Abstract
Objective
As an opportunistic pathogen, Nocardia often occurring in the immunocompromised hosts. As the unspecifc clinical presentation and low identification rate of the culture dependent methods, Nocardia infection may be under-diagnosis. Recent study have reported physicians could benefit from metagenomic next-generation sequencing (mNGS) in Nocardia diagnosis. Herein, we present patients with a positive detection of nocardiosis in mNGS, aiming to provide useful information for an differential diagnosis and patients management.

Methods
A total of 3756 samples detected for mNGS from March 2019 to April 2022 at the Fifth Affifiliated Hospital of Sun Yat-sen University, were screened. Clinical records, laboratory finding, CT images and mNGS results were reviewed for 19 patients who were positive for Nocardia genus.

Results
Samples from low respiratory tract obtained by bronchoscope took the major part of the positive (15/19). 12 of 19 cases were diagnosis as Nocardiosis Disease (ND) and over half of the ND individuals (7/12) were geriatric. Nearly all of them (10/12) were immunocompetent and 2 patients in ND group were impressively asymptomatic. Cough was the most common symptom. Nocardia cyriacigeorgica (4/12) was more frequently occurring in ND, followed by Nocardia abscessus (3/12). There are 3 individuals detected more than one kind of Nocardia species (Supplementary table 1). Except one with renal failure and one allergic to sulfamethoxazole, all of them received co-sulfonamide treatment and relieved eventually.

Conclusion
Our study deciphered the clinical features of patients with positive nocardiosis detected by mNGS. Greater attention should be paid to the ND that occurred in the immunocompetent host and the geriatric. Due to the difficulties in establishing diagnosis of Nocardiosis disease, mNGS should play a much more essential role for a better assessment in those intractable cases. Co-sulfonamide treatment should still be the first choice of Nocardiosis disease.
Bacterial profile and prevalence of urinary tract infections in pregnant women in Latin America: a systematic review and meta-analysis
Authors: de Souza Henrique Diório , Diório Giselle Rodrigues Mota , Peres Stela Verzinhasse , Francisco Rossana Pulcineli Vieira , Galletta Marco Aurélio Knippel 
Published: November 2023

Abstract
Background
Given the physiological changes during pregnancy, pregnant women are likely to develop recurrent urinary tract infections (UTIs) and pyelonephritis, which may result in adverse obstetric outcomes, including prematurity and low birth weight preeclampsia. However, data on UTI prevalence and bacterial profile in Latin American pregnant women remain scarce, necessitating the present systematic review to address this issue.

Methods
To identify eligible observational studies published up to September 2022, keywords were systematically searched in Medline/PubMed, Cochrane Library, Embase, Web of Science, and Bireme/Lilacs electronic databases and Google Scholar. The systematic review with meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the quality of studies was classified according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. The meta-analysis employed a random-effects method with double-arcsine transformation in the R software.

Results
Database and manual searches identified 253,550 citations published until September 2022. Among the identified citations, 67 met the inclusion criteria and were included in the systematic review, corresponding to a sample of 111,249 pregnant women from nine Latin American countries. Among Latin American pregnant women, the prevalence rates of asymptomatic bacteriuria, lower UTI, and pyelonephritis were estimated at 18.45% (95% confidence interval [CI]: 15.45–21.53), 7.54% (95% CI: 4.76–10.87), and 2.34% (95% CI: 0.68–4.85), respectively. Some regional differences were also detected. Among the included studies, Escherichia coli (70%) was identified as the most frequently isolated bacterial species, followed by Klebsiella sp. (6.8%).

Conclusion
Pregnant women in Latin America exhibit a higher prevalence of bacteriuria, UTI, and pyelonephritis than pregnant women globally. This scenario reinforces the importance of universal screening with urine culture during early prenatal care to ensure improved outcomes. Future investigations should assess the microbial susceptibility profiles of uropathogens isolated from pregnant women in Latin America.

Trial registration
This research was registered at PROSPERO (No. CRD42020212601).
Frequency of depression and correlates among Chinese children and adolescents living in poor areas under the background of targeted poverty alleviation: results of a survey in Weining county
Authors: Yuan Xiaofei , Hu Tingting , Zhu Xiaorui , Dong Sixin , Wang Gang , Chen Xu , Zhou Jiaojiao 
Published: November 2023

Abstract
Background
There is a lack of epidemiological data on depressive morbidity in children and adolescents in rural China. This study determines the frequency and correlates of depression among children and adolescents to offer useful insights for family education and government policy-making in rural China.

Methods
A cross-sectional online survey was conducted between April 20 to May 10, 2022. Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), and the correlative factors of depression were analyzed.

Results
In this study, 23,180 children and adolescents were enrolled (median (range) age: 12 (9–18) years); of them, 8,261 (35.6%) suffered from depression with a CES-D score of > 15. The onset of depression was significantly related to age, grade, gender, parental absence, attending key schools or classes, presence of moderate or severe internet addiction (IA), school record, social relationships, parental occupation, and education status. Furthermore, female gender (OR = 1.175; 95% CI: 1.108–1.247; p < 0.001), junior middle school (OR = 1.487; 95% CI: 1.380–1.601; p < 0.001), parental absence (OR = 1.272; 95% CI: 1.183–1.367; p < 0.001), attending key schools (OR = 1.221; 95% CI: 1.120–1.332; p < 0.001), attending key classes (OR = 1.099; 95% CI: 1.001–1.207; p = 0.048), and presence of moderate or above IA (OR = 13.593; 95% CI: 12.028–15.361; p < 0.001) were the most prominent independent factors for depression.

Conclusion
Depression is very common among Chinese children and adolescents living in poor areas of Weining County. Older age, higher school grade, female gender, parental absence, attending key schools or classes, and the presence of moderate to severe IA are some important factors that may dictate the occurrence of depression in these children and adolescents.
Effects of health education during public health emergencies on the health literacy, emotion and coping style of Chinese junior middle school students: a randomized controlled trial
Authors: Wang Zhou , Gao Tingye , Li Guangjian , Dong Gengjuan , Zhan Yan , Wang Bingqin , Sun Xugui 
Published: November 2023

Abstract
Background
Schools are high incidence places for public health emergencies. Good health literacy helps students cope with public health emergencies. Overall, the health literacy of young students is relatively low. Health education can promote health literacy, but the health education related to public health emergencies for Chinese junior middle school students needs to be improved. To design and implement health education courses related to public health emergencies for junior middle school students and examine the impact on their health literacy, emotions, and coping styles.

Methods
From March to December 2022, 724 students in Grade 7 and Grade 8 of two junior middle schools in Changzhou were randomly divided into a course group (n = 359) and a control group (n = 365). The course group received an age-appropriate health education course that addressed public health emergencies; there were 12 classes, one per week. The control group received general health education. One week before and after the courses, the two groups of students were assessed with the Adolescent Health Literacy Evaluation Scale under Public Health Emergencies (AHLES-PHE), the Depression Self-Rating Scale for Children (DSRSC), the Generalized Anxiety Disorder 7-item scale (GAD-7), and the Simplified Coping Style Questionnaire (SCSQ).

Results
After the courses were completed, the scores of AHLES-PHE [156.0 (45.0,180.0) vs. 165.0 (54.0,180.0), P < 0. 05] in the course group increased significantly. The positive rate of DSRSC [81 (22.6%) vs. 57 (15.9%), P < 0.05] and GAD-7 [45 (12.5%) vs. 29 (8.1), P < 0.05]in the course group were significantly lower than those before courses. There was no significant difference in the above indices before and after courses in the control group (P > 0.05).

Conclusion
This suggests that the health education courses related to public health emergencies designed in this study has an effect on improving health literacy, depression and anxiety in junior middle school students.
Comparison of short-term efficacy analysis of medium-rectal cancer surgery with robotic natural orifice specimen extraction and robotic transabdominal specimen extraction
Authors: Ye Shan-ping , Lu Wei-jie , Liu Dong-ning , Yu Hong-xin , Wu Can , Xu Hao-cheng , Li Tai-yuan 
Published: November 2023

Abstract
Background
With the development of minimally invasive technology, the trauma caused by surgery get smaller, At the same time, the specimen extraction surgery through the natural orifice is more favored by experts domestically and abroad, robotic surgery has further promoted the development of specimen extraction surgery through the natural orifice. The aim of current study is to compare the short-term outcomes of robotic-assisted natural orifice specimen extraction (NOSES ) and transabdominal specimen extraction(TRSE ) in median rectal cancer surgery.

Methods
From January 2020 to January 2023, 87 patients who underwent the NOSES or TRSE at the First Affiliated Hospital of Nanchang University were included in the study, 4 patients were excluded due to liver metastasis. Of these, 50 patients were in the TRSE and 33 patients in the NOSES. Short-term efficacy was compared in the two groups.

Results
The NOSES group had less operation time (P < 0.001), faster recovery of gastrointestinal function (P < 0.001), shorter abdominal incisions (P < 0.001), lower pain scores(P < 0.001). lower Inflammatory indicators of the white blood cell count and C-reactive protein content at 1, 3, and 5 days after surgery (P < 0.001, P = 0.037). There were 9 complications in the NOSES group and 11 complications in the TRSE group(P = 0.583). However, there were no wound complications in the NOSES group. The number of postoperative hospital stays seems to be same in the two groups. And there was no significant difference in postoperative anus function (P = 0.591).

Conclusions
This study shows that NOSES and TRSE can achieve similar radical treatment effects, NOSES is a feasible and safe way to take specimens for rectal cancer surgery in accordance with the indication for NOSES.