bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human papillomavirus disease in GATA2 deficiency: a genetic predisposition to HPV-associated female anogenital malignancy
Authors: Dancy Ehren , Stratton Pamela , Pichard Dominique C. , Marciano Beatriz E. , Cowen Edward W. , McBride Alison A. , Van Doorslaer Koenraad , Merideth Melissa A. , Salmeri Noemi , Hughes Marybeth S. , Heller Theo , Parta Mark , Hickstein Dennis D. , Kong Heidi H. , Holland Steven M. , Zerbe Christa S. 
Published: August 2024

ObjectivePatients with pathogenic variants in the GATA Binding Protein 2 (GATA2), a hematopoietic transcription factor, are at risk for human papillomavirus-related (HPV) anogenital cancer at younger than expected ages. A female cohort with GATA2 haploinsufficiency was systematically assessed by two gynecologists to characterize the extent and severity of anogenital HPV disease, which was also compared with affected males.MethodsA 17-year retrospective review of medical records, including laboratory, histopathology and cytopathology records was performed for patients diagnosed with GATA2 haploinsufficiency followed at the National Institutes of Health. Student’s t-test and Mann-Whitney U test or Fisher’s exact test were used to compare differences in continuous or categorical variables, respectively. Spearman’s rho coefficient was employed for correlations.ResultsOf 68 patients with GATA2 haploinsufficiency, HPV disease was the initial manifestation in 27 (40%). HPV occurred at median 18.9 (15.2-26.2) years in females, and 25.6 (23.4-26.9) years in males. Fifty-two (76%), 27 females and 25 males, developed HPV-related squamous intraepithelial lesions (SIL) including two males with oral cancer. Twenty-one patients developed anogenital high-grade SIL (HSIL) or carcinoma (16 females versus 5 males, (59% versus 20%, respectively, p=0.005) at median 27 (18.6-59.3) years for females and 33 (16.5-40.1) years for males. Females were more likely than males to require &gt;2 surgeries to treat recurrent HSIL (p=0.0009). Of 30 patients undergoing hematopoietic stem cell transplant (HSCT) to manage disease arising from GATA2 haploinsufficiency, 12 (nine females, three males) had persistent HSIL/HPV disease. Of these nine females, eight underwent peri-transplant surgical treatment of HSIL. Five of seven who survived post-HSCT received HPV vaccination and had no or minimal evidence of HPV disease 2 years post-HSCT. HPV disease persisted in two receiving immunosuppression. HPV disease/low SIL (LSIL) resolved in all three males.ConclusionFemales with GATA2 haploinsufficiency exhibit a heightened risk of recurrent, multifocal anogenital HSIL requiring frequent surveillance and multiple treatments. GATA2 haploinsufficiency must be considered in a female with extensive, multifocal genital HSIL unresponsive to multiple surgeries. This population may benefit from early intervention like HSCT accompanied by continued, enhanced surveillance and treatment by gynecologic oncologists and gynecologists in those with anogenital HPV disease.
Evaluating the efficacy and safety of different neoadjuvant immunotherapy combinations in locally advanced HNSCC: a systematic review and meta-analysis
Authors: Liu Chang , Li Mingzhu , Liu Xiaojie , Shi Ting , Wang Yun , Sui Chaoyang , Zhang Wenan , Wang Bowen 
Published: August 2024

BackgroundImmune checkpoint inhibitors have demonstrated promising therapeutic outcomes in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC), prompting numerous clinical trials to investigate the safety and efficacy of this approach in neoadjuvant therapy. This systematic review aims to consolidate and analyze the findings from various clinical trials combining neoadjuvant immunotherapy for HNSCC, with the goal of identifying the most effective neoadjuvant immunotherapy regimen.MethodsThe system conducted searches across electronic databases including PubMed, Embase, the Cochrane Library and Web of science from their inception to July 1, 2024. The primary focus was on evaluating efficacy (particularly pathological complete response (pCR), major pathological response (MPR), and overall response rate (ORR)) and safety (primarily assessed by grade 3-4 treatment-related adverse reactions).ResultsA total of 1943 patients from 32 studies were analyzed. Combining neoadjuvant immunotherapy with chemotherapy or radiotherapy demonstrated superiority over neoadjuvant immunotherapy alone in terms of the MPR rate, while showing no statistically significant difference in the pCR rate. Furthermore, the combination of neoadjuvant immunotherapy with chemotherapy or radiotherapy exhibited a lower CR rate compared to neoadjuvant immunotherapy with radiotherapy alone, but a higher PR rate and SD rate. Apart from the neoadjuvant immunotherapy group in isolation, there were no statistically significant differences in grade ≥3 treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) among the other three combination therapy groups.ConclusionThis systematic review and meta-analysis indicate that patients with locally advanced HNSCC might benefit from neoadjuvant immunotherapy, particularly when used in conjunction with chemotherapy or radiotherapy. Nonetheless, additional data is required to definitively confirm its efficacy.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=553753, identifier CRD42024553753.
Cancellation of the more complicated ophthalmic inpatient surgeries in a tertiary general hospital: a 10-year retrospective study
Authors: Zhao Xinyu , Zhao Qing , Wu Yanfang , Cheng Shiyu , Wang Chuting , Meng Lihui , Gu Xingwang , Chen Youxin 
Published: August 2024

BackgroundAlthough ophthalmic ambulatory surgeries are less costly and may enhance the more efficient utilization of hospital resources, inpatient surgeries were preferable alternatives for patients with complicated eye diseases or poor general health. However, the incidence, causes, and related factors of ophthalmic inpatient surgery cancellation remained largely unknown.MethodsThe electronic medical records of ophthalmic inpatient surgeries between January 2012 and December 2022 was retrospectively reviewed. Cancellation-related factors were explored using multivariate logistic regression analysis and the reasons of cancellation were also evaluated.ResultsIn total, 820 cancelled surgeries and 42,073 performed surgeries were included, with a cancellation rate of 1.9%. Any other ocular comorbidities were risk factors for cancellation (odds ratio (OR) 1.872, 95% confidence intervals (CI) 1.504–2.331; p &lt; 0.001), while older age (OR 0.990, 95% CI 0.986–0.995; p &lt; 0.001), local residence (OR 0.809, 95% CI 0.692–0.947; p = 0.008), any systemic comorbidities (OR 0.740, 95% CI 0.616–0.889; p = 0.001), and previous history of surgeries (OR 0.403, 95% CI 0.341–0.476; p &lt; 0.001) were negatively associated with surgery cancellation. The top two categorical cancellation reasons were medical factors (508, 62.0%) and patient-related factors (285, 34.8%). “Patient/family refused surgery” (127, 15.5%), “acute conjunctivitis or uveitis relapse” (103, 12.6%), and “ocular condition improved and procedure no longer indicated” (71, 8.7%) were the three most common single cancellation reasons.ConclusionAny other ocular comorbidities, younger age, no systemic comorbidities, non-local residence, and no past surgical history were related factors for ophthalmic inpatient surgery cancellation. The majority of cancellations were due to patient-related or medical factors. Great importance should be attached to the cancellation of the more complicated inpatient surgeries and further efforts are warranted to explore how to reduce cancellation.
Elucidation of mechanisms underlying active oxygen burst in Citrus sinensis after Diaporthe citri infection using transcriptome analysis
Authors: Liu Tiantian , Zhou Zehua , Luo Changwei , Luo Hua , Tang Jun , Shi Xiaojiang , Li Diping , Zhang Qiong , Li Jin , Xia Yonggang , Song Na , Yi Tuyong 
Published: August 2024

IntroductionReactive oxygen species (ROS) generation is a common disease defense mechanism in plants. However, it is unclear whether Citrus host activates defense response against Diaporthe citri causing citrus melanose disease by producing ROS, and the underlying molecular mechanisms are unknown.MethodsDAB staining and RNA-Seq technology were used to compare the active oxygen burst and differential gene expression, respectively, in uninfected and infected Citrus sinensis leaves at different time points during D. citri infection in vivo. The functions of CsRBOH (a significant DEG) were confirmed in N. benthamiana through the Agrobacterium-mediated transient expression system.ResultsDAB staining indicated that C. sinensis initiated defense against D. citri infection within 24 h by generating ROS. Illumina sequencing revealed 25,557 expressed genes of C. sinensis. The most upregulated DEGs (n = 1,570) were identified 72 h after fungal inoculation (sample denoted as CD72). In the CD72 vs. Cs (samples at 0 h after fungal inoculation) comparison, the KEGG pathway category with the highest number of genes (n = 62) and most significant enrichment was Protein processing in endoplasmic reticulum, followed by Glutathione metabolism and MAPK signaling pathway-plant. GO analysis revealed that the DEGs of CD72 vs. Cs related to active oxygen burst and chitin recognition were significantly grouped into the regulation of biological processes and molecular functions, with GO terms including response to ROS, response to fungus, and oxidoreductase activity. Remarkably, CsRBOH was significantly enriched in the GO and KEGG analyses, and its expression pattern in qRT-PCR and DAB staining results were consistent. Among the 63 ROS-related DEGs, HSP genes and genes associated with the peroxidase family were highly significant as revealed by protein–protein interaction networks. Furthermore, ROS accumulation, cell death, and upregulation of defense-related genes were observed in N. benthamiana leaves with CsRBOH expressed through the Agrobacterium-mediated transient expression system.ConclusionOur findings suggested that C. sinensis activates CsRBOH and ROS-related genes, leading to ROS accumulation to resist the invasion by D. citri. This study laid the foundation for future research on molecular mechanisms and breeding of C. sinensis cultivars resistant to citrus melanose.
Genes associated with fitness and disease severity in the pan-genome of mastitis-associated Escherichia coli
Authors: Olson Michael A. , Cullimore Caz , Hutchison Weston D. , Grimsrud Aleksander , Nobrega Diego , De Buck Jeroen , Barkema Herman W. , Wilson Eric , Pickett Brett E. , Erickson David L. 
Published: August 2024

IntroductionBovine mastitis caused by Escherichia coli compromises animal health and inflicts substantial product losses in dairy farming. It may manifest as subclinical through severe acute disease and can be transient or persistent in nature. Little is known about bacterial factors that impact clinical outcomes or allow some strains to outcompete others in the mammary gland (MG) environment. Mastitis-associated E. coli (MAEC) may have distinctive characteristics which may contribute to the varied nature of the disease. Given their high levels of intraspecies genetic variability, virulence factors of commonly used MAEC model strains may not be relevant to all members of this group.MethodsIn this study, we sequenced the genomes of 96 MAEC strains isolated from cattle with clinical mastitis (CM). We utilized clinical severity data to perform genome-wide association studies to identify accessory genes associated with strains isolated from mild or severe CM, or with high or low competitive fitness during in vivo competition assays. Genes associated with mastitis pathogens or commensal strains isolated from bovine sources were also identified.ResultsA type-2 secretion system (T2SS) and a chitinase (ChiA) exported by this system were strongly associated with pathogenic isolates compared with commensal strains. Deletion of chiA from MAEC isolates decreased their adherence to cultured bovine mammary epithelial cells.DiscussionThe increased fitness associated with strains possessing this gene may be due to better attachment in the MG. Overall, these results provide a much richer understanding of MAEC and suggest bacterial processes that may underlie the clinical diversity associated with mastitis and their adaptation to this unique environment.
Speed of processing training to improve cognition in moderate to severe TBI: a randomized clinical trial
Authors: Chiaravalloti Nancy D. , Costa Silvana L , Armknecht Caroline , Costanza Kristin , Wallace Sean , Moore Nancy B. , DeLuca John 
Published: August 2024

BackgroundModerate to severe traumatic brain injury (TBI) often results in cognitive deficits. Processing speed (PS) deficits are common, exerting a significant impact on daily life. Few studies have examined the efficacy of cognitive rehabilitation specifically for PS deficits in moderate to severe TBI.ObjectiveExamine the efficacy of Speed of Processing Training (SOPT) in moderate to severe TBI. This protocol is a 10-session behavioral intervention for PS deficits that has been successfully used with other cognitively impaired populations.MethodsThis double-blind, placebo-controlled, randomized clinical trial included 46 participants with moderate to severe TBI, 22 randomly assigned to the treatment group and 24 to the placebo-control group. Baseline and follow-up measures included a task similar to the training task (UFOV), measures of near transfer (neuropsychological measures of processing speed: Symbol Digit Modalities Test (SDMT), Wechsler Adult Intelligence Scale-IV (WAIS-IV) Symbol Search, WAIS-IV Coding) and measures of far transfer [neuropsychological measures of learning and memory: the California Verbal Learning Test-II (CVLT-II), Memory Assessment Scales - Prose Memory (MAS-PM)].ResultsSignificant improvement from pre-to post-SOPT was observed on all subtests of the UFOV, which is similar to the training task. There was no significant difference on neuropsychological measures of PS or new learning and memory post-treatment. Neuropsychological assessment 6-months post-treatment showed no significant change in PS ability over time. Monthly booster sessions did not impact performance at the 6-month follow-up.ConclusionConsistent with the SOPT literature, SOPT improves PS ability as measured by the UFOV, a task similar to the training task, in moderate to severe TBI. However, neither near nor far transfer was noted. That is, no improvement was noted on neuropsychological measures of PS.
Research trends on cancer neuroscience: a bibliometric and visualized analysis
Authors: Ma Xinru , Deng Kun , Sun Yingnan , Wu Minghua 
Published: August 2024

BackgroundRecently, cancer neuroscience has become the focus for scientists. Interactions between the nervous system and cancer (both systemic and local) can regulate tumorigenesis, progression, treatment resistance, compromise of anti-cancer immunity, and provocation of tumor-promoting inflammation. We assessed the related research on cancer neuroscience through bibliometric analysis and explored the research status and hotspots from 2020 to 2024.MethodsPublications on cancer neuroscience retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and Scimago Graphica were used to analyze and visualize the result.ResultsA total of 744 publications were retrieved, with an upward trend in the overall number of articles published over the last 5 years. As it has the highest number of publications (n = 242) and citations (average 13.63 citations per article), the United States holds an absolute voice in the field of cancer neuroscience. The most productive organizations and journals were Shanghai Jiaotong University (n = 24) and Cancers (n = 45), respectively. Monje M (H-index = 53), Hondermarck H (H-index = 42), and Amit M (H-index = 39) were the three researchers who have contributed most to the field. From a global perspective, research hotspots in cancer neuroscience comprise nerve/neuron-tumor cell interactions, crosstalk between the nervous system and other components of the tumor microenvironment (such as immune cells), as well as the impact of tumors and tumor therapies on nervous system function.ConclusionThe United States and European countries are dominating the field of cancer neuroscience, while developing countries such as China are growing rapidly but with limited impact. The next focal point in this field is likely to be neurotrophic factors. Cancer neuroscience is still in its infancy, which means that many of the interactions and mechanisms between the nervous system and cancer are not yet fully understood. Further investigation is necessary to probe the interactions of the nervous system with cancer cell subpopulations and other components of the tumor microenvironment.
Prognosis in HR-positive metastatic breast cancer with HER2-low versus HER2-zero treated with CDK4/6 inhibitor and endocrine therapy: a meta-analysis
Authors: Xia Lin-Yu , Cao Xu-Chen , Hu Qing-Lin , Xu Wei-Yun 
Published: August 2024

BackgroundThe combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) is currently the standard first-line treatment for patients with metastatic hormone receptor positive (HR+), and HER2-negative (HER2-) breast cancer. However, the impact of HER2 status on the prognosis of patients receiving CDK4/6i and ET remains unclear. The meta-analysis was conducted to evaluate different outcomes between HER2-low and HER2-zero patients in advanced HR+ breast cancer receiving CDK4/6i and ET.MethodsA systematic search was performed in PubMed and EMBASE databases for relevant published literature. Objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) were pooled by fixed or random effects models.ResultsOverall, 12 studies with 3567 patients were eligible for analysis. The pooled analysis suggested that no significant differences were observed in terms of ORR and OS between HER2-low and HER2-zero patients who underwent CDK4/6i and ET. Similarly, no significant difference in PFS was found between HER2-low and HER2-zero patients who underwent post-line CDK4/6i and ET or first-line Palbociclib and ET. However, in patients who received mixed-line (not a single treatment line) or first-line CDK4/6i and ET, the PFS was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup (mixed-line: HR = 1.36; 95% CI = 1.11–1.65; P = 0.002; first-line: HR = 1.14; 95% CI = 1.01–1.28; P = 0.04). A similar phenomenon was observed in patients who received mixed-line or post-line Palbociclib and ET (mixed-line: HR = 1.60; 95% CI = 1.09–2.34; P = 0.02; post-line: HR = 1.43; 95% CI = 1.03–2.00; P = 0.03).ConclusionThese results indicated that HER2-low status did not have a significant association with ORR and OS, but it may have a worse impact on PFS in patients who received mixed-line or first-line CDK4/6i and ET, as well as mixed-line or post-line palbociclib plus ET.
The antitumor effect of diisopropylamine dichloroacetate on non-small cell lung cancer and its influence on the tumor immune microenvironment
Authors: Wei Min , Shen Xiaoyan , Liu Ye , Chen Xiaotong , Su Shu , Lv Xin , Qian Xiaoping , Yu Lixia , Wang Lifeng 
Published: August 2024

ObjectiveTo evaluate the antitumor effects of diisopropylamine dichloroacetate (DADA) alone or in combination with chemotherapy/radiotherapy/immunotherapy in NSCLC and explore the underlying mechanisms involved.MethodsMTT, UV spectrophotometry, flow cytometry, fluorescence microscopy, and clonogenic survival assays were used. In LLC mouse models, the antitumor effects of radiotherapy, DADA, and the anti-PD-1 antibody alone or in combination were evaluated, and the T cell numbers were evaluated in different groups.ResultsDADA significantly inhibited lactate production and promoted apoptosis in NSCLC in vitro. Compared with pemetrexed or DADA alone, the combination of DADA with pemetrexed significantly inhibited proliferation and promoted apoptosis (p&lt;0.05). This may be related to the decrease in the mitochondrial membrane potential in the combined group. Moreover, compared with radiotherapy alone, the combination of DADA with radiotherapy induced remarkable DNA damage. In vivo, the combination of radiotherapy, an anti-PD-1 antibody and DADA resulted in superior tumor inhibition than the combination of radiotherapy and anti-PD-1 antibody did (p &lt; 0.05). The underlying mechanism may be partially related to the increased number of CD3+ T cells in the triplet combination group (p &lt; 0.05).DiscussionOur results showed that DADA has strong antitumor effects on NSCLC, either alone or in combination with chemotherapy or radiotherapy. Interestingly, the combination of radiotherapy, anti-PD-1 antibody and DADA had a more pronounced tumor-suppressing effect, which may be related to DADA-induced T-cell generation by reducing local lactic acid production in the tumor microenvironment. This study lays the foundation for further exploration of DADA in lung cancer, especially in the era of immunotherapy, on the basis of its possible immunomodulatory effects.
Markers of chronic disease risk in term low birthweight Indian children aged 8–14 years
Authors: Gusain Yamini , Malik Anku , Filteau Suzanne , Pathak Renuka , Sachdev Harshpal Singh , Trilok-Kumar Geeta 
Published: August 2024

BackgroundLow birth weight (LBW) is a public health problem in India with consequences in the short and long term. It increases the risk of obesity and its related comorbidities including type 2 diabetes and cardiovascular disease (CVD) in later life. This study aimed to assess the risk markers of chronic disease in term born low birthweight Indian children aged 8–14 years.MethodsThis was a cross-sectional follow-up of LBW children from DIViDS (Delhi Infant Vitamin D Supplementation) cohort and involved assessment of their anthropometric measurements, body composition, levels of adipokines and biomarkers of chronic diseases. Neighbourhood children born normal birth weight (NBW) (&gt;2.5 kg) were enrolled for comparison.ResultsThe study included 667 LBW and 87 NBW children. Height-for-age, body mass index for-age (BMIZ), fat-free mass index, and waist circumference of LBW children were lower than those of NBW children. LBW children could jump farther. LBW children who were now overweight had higher leptin, triglyceride and VLDL and lower HDL, compared to NBW children in the same BMIZ category. Currently underweight LBW children had higher adiponectin and lower leptin levels than the reference group. There were no differences between LBW and NBW children in visfatin, fasting glucose and insulin, hemoglobin A1c, triglyceride, low density lipoprotein or C-reactive protein.ConclusionAt 8–14 years few children were overweight and there were few differences in some risk markers of chronic disease between LBW and NBW children. Overweight, which was associated with some increased risk markers, may increase with age, thus timely counselling and monitoring of these LBW children will be important to mitigate these risks.