bluuebunny/crossref_metadata_2025_split huggingface dataset:
The alteration of intrauterine microbiota in chronic endometritis patients based on 16S rRNA sequencing analysis
Authors: Chen Qing , Zhang Xiaowei , Hu Qicai , Zhang Wei , Xie Yi , Wei Weixia 
Published: January 2023

Abstract
Background
Chronic endometritis (CE) is a disease of continuous and subtle inflammation occurring in the endometrial stromal area, which is often asymptomatic or present with non-specific clinical symptoms.

Methods
This study investigated the composition and distribution of the intrauterine microbiota of 71 patients who underwent hysteroscopy during the routine clinical inspection of infertility. Among them, patients who were diagnosed with chronic endometritis (CE) were allocated into CE group (n = 29) and others into non-CE group (n = 42). There was no significant difference in average age between the two groups (P = 0.19). Uterine flushing fluid was collected by the self-developed cervical trocar uterine cavity sampler and 16S rRNA sequencing was performed.

Results
The alpha diversity in the CE group was significantly higher than that in the non-CE group (P < 0.05). Firmicutes (newly named Bacillota) were the dominant phylum in the non-CE group (72.23%), while their abundance was much lower in the CE group (49.92%), but there was no statistically significant difference between the two groups. The abundances of Actinobacteriota and Cyanobacteria in the CE group were significantly higher than those in the non-CE group (P < 0.05). At the genus level, the abundance of Lactobacillus dominated in all samples, which presented a significantly lower abundance in the CE group (40.88%) than that in the non-CE group (64.22%) (P < 0.05). Correspondingly, the abundance of non-Lactobacillus was higher in the CE group, among which Pseudomonas and Cutibacterium increased significantly (P < 0.01). Moreover, compared with the non-CE group, the pathways involved in arginine and proline metabolism and retinol metabolism were significantly enriched in the CE group (P < 0.05), while the metabolism of lipid and prenyltransferases were significantly decreased in the CE group (P < 0.05).

Conclusions
A certain microbial community was colonized in the uterine cavity, which was dominated by Lactobacillus. The structure and distribution of intrauterine microbiota in the CE group were different from those in the non-CE group by showing a lower abundance of Lactobacillus, and a significantly higher abundance of Pseudomonas and Cutibacterium. Additionally, the microbial metabolism was altered in the CE group. This study elaborated the alteration of intrauterine microbiota in CE patients, which may contribute to the diagnosis of CE and provide a reference for antibiotic treatment of CE.
Advancements in nanoparticle-based treatment approaches for skin cancer therapy
Authors: Zeng Leli , Gowda B. H. Jaswanth , Ahmed Mohammed Gulzar , Abourehab Mohammed A. S. , Chen Zhe-Sheng , Zhang Changhua , Li Jia , Kesharwani Prashant 
Published: January 2023

AbstractSkin cancer has emerged as the fifth most commonly reported cancer in the world, causing a burden on global health and the economy. The enormously rising environmental changes, industrialization, and genetic modification have further exacerbated skin cancer statistics. Current treatment modalities such as surgery, radiotherapy, conventional chemotherapy, targeted therapy, and immunotherapy are facing several issues related to cost, toxicity, and bioavailability thereby leading to declined anti-skin cancer therapeutic efficacy and poor patient compliance. In the context of overcoming this limitation, several nanotechnological advancements have been witnessed so far. Among various nanomaterials, nanoparticles have endowed exorbitant advantages by acting as both therapeutic agents and drug carriers for the remarkable treatment of skin cancer. The small size and large surface area to volume ratio of nanoparticles escalate the skin tumor uptake through their leaky vasculature resulting in enhanced therapeutic efficacy. In this context, the present review provides up to date information about different types and pathology of skin cancer, followed by their current treatment modalities and associated drawbacks. Furthermore, it meticulously discusses the role of numerous inorganic, polymer, and lipid-based nanoparticles in skin cancer therapy with subsequent descriptions of their patents and clinical trials.
Graphical Abstract
CircNDC80 promotes glioblastoma multiforme tumorigenesis via the miR-139-5p/ECE1 pathway
Authors: Wang Yuhang , Wang Binbin , Zhou Fengqi , Lv Kun , Xu Xiupeng , Cao Wenping 
Published: January 2023

Abstract
Background
Circular RNAs (circRNAs) have been shown to be essential for the emergence and growth of different cancers. However, further research is required to validate the function of circRNA in glioblastoma (GBM).

Methods
CircNDC80 expression in both normal brain tissues (NBTs) and glioma tissues was determined using real-time PCR. The impact of circNDC80 on GBM cell proliferation, migration, and invasion was then confirmed by CCK-8, colony formation, EdU incorporation, Transwell, and wound healing assays. To determine how circNDC80 affects the capacity of glioma stem cells (GSCs) to maintain their stemness and self-renewal, a CellTiter-Glo assay, clonogenic assay and extreme limiting dilution assay were utilized. To ascertain the impact of circNDC80 in vivo, intracranial xenograft models were established.

Results
When compared to NBT, glioblastoma tissue had a higher level of circNDC80 expression. In functional assays, circNDC80 promoted glioblastoma cell proliferation, migration, and invasion, while sustaining the stemness and fostering the self-renewal of glioma stem cells. In addition, a dual luciferase reporter assay and circRIP were used to verify that circNDC80 simultaneously affects the expression of ECE1 mRNA by sponging miR-139-5p, and a rescue experiment was used to verify the above results further.

Conclusions
According to our research, circNDC80 is an oncogenic factor that promotes glioblastoma through the miR-139-5p/ECE1 pathway. This implies that circNDC80 may be employed as a novel therapeutic target and a possible predictive biomarker.
A machine learning framework develops a DNA replication stress model for predicting clinical outcomes and therapeutic vulnerability in primary prostate cancer
Authors: Huang Rong-Hua , Hong Ying-Kai , Du Heng , Ke Wei-Qi , Lin Bing-Biao , Li Ya-Lan 
Published: January 2023

AbstractRecent studies have identified DNA replication stress as an important feature of advanced prostate cancer (PCa). The identification of biomarkers for DNA replication stress could therefore facilitate risk stratification and help inform treatment options for PCa. Here, we designed a robust machine learning-based framework to comprehensively explore the impact of DNA replication stress on prognosis and treatment in 5 PCa bulk transcriptomic cohorts with a total of 905 patients. Bootstrap resampling-based univariate Cox regression and Boruta algorithm were applied to select a subset of DNA replication stress genes that were more clinically relevant. Next, we benchmarked 7 survival-related machine-learning algorithms for PCa recurrence using nested cross-validation. Multi-omic and drug sensitivity data were also utilized to characterize PCa with various DNA replication stress. We found that the hyperparameter-tuned eXtreme Gradient Boosting model outperformed other tuned models and was therefore used to establish a robust replication stress signature (RSS). RSS demonstrated superior performance over most clinical features and other PCa signatures in predicting PCa recurrence across cohorts. Lower RSS was characterized by enriched metabolism pathways, high androgen activity, and a favorable prognosis. In contrast, higher RSS was significantly associated with TP53, RB1, and PTEN deletion, exhibited increased proliferation and DNA replication stress, and was more immune-suppressive with a higher chance of immunotherapy response. In silico screening identified 13 potential targets (e.g. TOP2A, CDK9, and RRM2) from 2249 druggable targets, and 2 therapeutic agents (irinotecan and topotecan) for RSS-high patients. Additionally, RSS-high patients were more responsive to taxane-based chemotherapy and Poly (ADP-ribose) polymerase inhibitors, whereas RSS-low patients were more sensitive to androgen deprivation therapy. In conclusion, a robust machine-learning framework was used to reveal the great potential of RSS for personalized risk stratification and therapeutic implications in PCa.
The uptake of key elements of sexual and reproductive health services and its predictors among rural adolescents in Southern Ethiopia, 2020: application of a Poisson regression analysis
Authors: Habte Aklilu , Dessu Samuel 
Published: January 2023

Abstract
Background
Although 25% of the Ethiopian population is young, Sexual and Reproductive Health (SRH) Services have not been adequately researched and intervened, leaving adolescents with many reproductive health challenges. Assessment of the uptake of each element of SRH service and its determinants among those age groups is essential to improving service uptake and reducing the burden of illness and disability in adolescents. Thus, this study aimed at assessing the uptake of key elements of SRH services and its determinants among adolescents residing in rural districts of Guraghe zone, Southern Ethiopia.

Methods
A community-based cross-sectional study was carried out from May 1 to 30, 2020, and a multi-stage sampling technique was employed to randomly select 1028 adolescents. The data were collected by using a pre-tested interviewer-administered questionnaire. The data were coded and entered into Epi-Data version 3.1 and exported into SPSS version 23 for analysis. Independent t-tests and analysis of variance (ANOVA) were run to determine whether there were statistically significant differences in the mean number of SRH services used across each categorical variable. A multivariable generalized linear regression (GLM) model with a Poisson link was used to determine the effect of each variable on the mean number of SRH services used. Adjusted odds ratios with their corresponding 95% confidence interval were used to declare the statistical significance of the independent variables.

Results
The study included 1,009 adolescents, yielding a response rate of 98.1%. The use of the SRH service was assessed using eight elements, and the mean (± SD) score of service uptake was 4.05 (± 1.94), with only 6.8% of adolescents receiving all key elements. Comprehensive sexuality education (55.1%) and voluntary HIV/AIDS counseling and testing (51.0%) were the commonest service items used by adolescents, while the provision of contraceptives was the lowest service item received (25.9%). Educational level (AOR: 1.28, 95% CI: 1.03–1.56), having a parental discussion (AOR: 1.31, 95% CI: 1.13–1.51), lack of youth clubs (AOR: 0.71, 95% CI: 0.66–0.87), and knowledge on SRH issues (AOR: 0.79, 95% CI: 0.73–0.85) were identified as significant predictors of the uptake of key elements of SRH services.

Conclusion
The overall uptake of SRH services was found to be low in the study area. Schools should be an excellent means of educating adolescents to increase their knowledge of key elements of SRH services. Furthermore, stakeholders must work together to improve the culture of parental discussion with adolescents and establish and strengthen youth clubs, as measures for encouraging the use of SRH services.
Assessing cultural competency among Canadian chiropractors: a cross-sectional survey of Canadian Chiropractic Association members
Authors: Bakaa Nora , Southerst Danielle , Côté Pierre , Macedo Luciana , Carlesso Lisa C. , MacDermid Joy , Mior Silvano 
Published: January 2023

AbstractBackgroundThere is a paucity of research assessing cultural competency among Canadian chiropractors. Therefore, the aims of this study were to (1) measure cultural competency among Canadian chiropractors, (2) understand chiropractors’ perspectives of challenges and attitudes regarding the delivery of chiropractic services to equity-seeking communities, and (3) assess contextual factors associated with cultural competency.MethodsWe conducted a cross-sectional survey of members of the Canadian Chiropractic Association (CCA) (May–July 2021). The survey instrument consisted of 57 questions related to demographics, cultural competency, perceptions about health disparities, and challenges in delivery of rehabilitation. Cultural competency was measured using the Cultural Awareness and Sensitivity and Cultural Competence Behaviours subscales of the Cultural Competence Assessment Instrument. We conducted a multivariate linear regression to assess factors that may be associated with cultural competency.ResultsA total of 3143 CCA members responded (response rate of 41%). Mean scores for the Cultural Awareness and Sensitivity subscale were 5.8/7 (95% CI 5.7; 5.8) and 4.2/7 (95% CI 4.1; 4.2) for the Cultural Competence Behaviour subscale. Most chiropractors (72–78%) reported observing important cultural health disparities across various care-related outcomes. Cost of services and language were identified as barriers to providing care to equity-seeking communities. Cultural Awareness and Sensitivity scores were weakly associated with gender (men), years of clinical practice, cultural health disparities, the statement “I think some people have an agenda to look for discrimination even where it does not exist (DEI attitudes),” race (Caucasian), and prior DEI training, (R2 = 0.15,p < 0.0001). Cultural Competence Behaviour scores were weakly associated with race (Caucasian), cultural health disparities, prior DEI training, increased years of clinical experience, and higher Cultural Awareness and Sensitivity scores (R2 = 0.19,p < 0.0001).ConclusionThis study provides the first description of cultural competency within the chiropractic profession in Canada. Findings suggest a gap between knowledge and behaviour and uncover several barriers and challenges that may inform the development of profession-specific training in cultural competence.
COVID-19: critical case of a patient with an atypical manifestation of the disease
Authors: Barrón-Palma Eira Valeria , Ríos-Zaragoza Siddhartha , Sanchez-Sandoval Ana Laura 
Published: January 2023

AbstractBackgroundCOVID-19 was initially described as a severe acute respiratory disease that could drive to pneumonia, compromising the life of the patients in the worst scenario. However, even though in most of the cases the respiratory symptoms are still the most common manifestations of the disease, nowadays it is considered as a complex multisystem illness, affecting a variety of organs and tissues. Asymptomatic and atypic cases have also been described, where symptoms are not related to those first described, as is the case of this report.Case presentationOn November 23, 2020, a 53-year-old woman goes to the emergency room due to gastrointestinal symptoms. The admission diagnosis was inflammatory bowel disease and a mild event of idiopathic chronic ulcerative colitis, and the initial treatment was focused on the metabolic acidosis, and the reestablishment the hydroelectrolytic and hemodynamic balance. Then, she was transferred to the Gastroenterology Unit where she was treated for one week. During her hospitalization, she showed a refractory shock caused by progressive organ deterioration (renal and neurological), requiring a double-vasopressor support, oxygenation, and ventilation. Considering the laboratory tests results and computed tomography scans, a COVID-19 test was carried out, obtaining a positive result with a high viral load. The S gene of the virus was amplified and sequenced, finding an uncommon mutation rarely reported worldwide. After considerable systemic deterioration, the patient presented cardiorespiratory arrest, with no response and died on December 1, after 8 days of hospitalization.ConclusionsIn this report we describe the pathogenesis, clinical manifestations, and outcome of a patient with atypical COVID-19 symptoms (mainly gastrointestinal), rapidly evolving and with lethal consequences. Therefore, it is important to emphasize the need to strengthen patient surveillance in health centers, including those who do not present typical symptoms of COVID-19.In addition, it will be important to track the identified mutation (H1058Y) in the S viral gene and assess whether it could be associated with a different clinical manifestation of the disease or if it was just an isolated event.
On-treatment derived neutrophil-to-lymphocyte ratio and survival with palbociclib and endocrine treatment: analysis of a multicenter retrospective cohort and the PALOMA-2/3 study with immune correlates
Authors: Kim Chang Gon , Kim Min Hwan , Kim Jee Hung , Kim Seul-Gi , Kim Gun Min , Kim Tae Yeong , Ryu Won-Ji , Kim Jee Ye , Park Hyung Seok , Park Seho , Cho Young Up , Park Byeong Woo , Kim Seung Il , Jeong Joon , Sohn Joohyuk 
Published: January 2023

Abstract
Background
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated.

Methods
Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics.

Results
In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P < 0.001). In the PALOMA-2 validation cohort, higher on-treatment dNLRs were associated with inferior PFS in patients treated with palbociclib and letrozole (hazard ratio = 1.498, P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency.

Conclusions
On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment.
Systemic interindividual epigenetic variation in humans is associated with transposable elements and under strong genetic control
Authors: Gunasekara Chathura J. , MacKay Harry , Scott C. Anthony , Li Shaobo , Laritsky Eleonora , Baker Maria S. , Grimm Sandra L. , Jun Goo , Li Yumei , Chen Rui , Wiemels Joseph L. , Coarfa Cristian , Waterland Robert A. 
Published: January 2023

Abstract
Background
Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition.

Results
We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program. At CoRSIVs, DNA methylation in peripheral blood correlates with methylation and gene expression in internal organs. We also discover unprecedented mQTL at these regions. Genetic influences on CoRSIV methylation are extremely strong (median R2=0.76), cumulatively comprising over 70-fold more human mQTL than detected in the most powerful previous study. Moreover, mQTL beta coefficients at CoRSIVs are highly skewed (i.e., the major allele predicts higher methylation). Both surprising findings are independently validated in a cohort of 47 non-GTEx individuals. Genomic regions flanking CoRSIVs show long-range enrichments for LINE-1 and LTR transposable elements; the skewed beta coefficients may therefore reflect evolutionary selection of genetic variants that promote their methylation and silencing. Analyses of GWAS summary statistics show that mQTL polymorphisms at CoRSIVs are associated with metabolic and other classes of disease.

Conclusions
A focus on systemic interindividual epigenetic variants, clearly enhanced in mQTL content, should likewise benefit studies attempting to link human epigenetic variation to the risk of disease.
The effects of imaging markers on clinical trajectory in cerebral amyloid angiopathy: a longitudinal study in a memory clinic
Authors: Jang Hyemin , Chun Min Young , Kim Hee Jin , Na Duk L. , Seo Sang Won 
Published: January 2023

Abstract
Background
We investigated the relevance of various imaging markers for the clinical trajectory of cerebral amyloid angiopathy (CAA) patients in a memory clinic.

Methods
A total of 226 patients with probable CAA were included in this study with a mean follow-up period of 3.5 ± 2.7 years. Although all had more than one follow-up visit, 173 underwent follow-up Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SB) ranging from 2 to 15 time points. Among 226, 122 patients underwent amyloid-β (Aβ) PET imaging. The prevalence of intracerebral hemorrhage (ICH) and its imaging predictors was investigated. The effects of CAA imaging markers and Aβ PET positivity on longitudinal cognition based on the MMSE and CDR-SB were evaluated using mixed effects models.

Results
During the follow-up, 10 (4.4%) patients developed ICH: cortical superficial siderosis (cSS; hazard ratio [HR], 6.45) and previous lobar ICH (HR, 4.9), but lobar cerebral microbleeds (CMBs) were not predictors of ICH development. The presence of CMIs (p = 0.045) and Aβ positivity (p = 0.002) were associated with worse MMSE trajectory in CAA patients. Regarding CDR-SB trajectory, only Aβ positivity was marginally associated with worse longitudinal change (p = 0.050).

Conclusion
The results of the present study indicated that various imaging markers in CAA patients have different clinical relevance and predictive values for further clinical courses.