bluuebunny/crossref_metadata_2025_split huggingface dataset:
Based polymer nanoparticles from bee pollen attenuate non-small lung cancer through enhancement of apoptosis and cell cycle arrest in vivo
Authors: Salim Elsayed I. , Mahfouz Magdy E. , Eltonouby Eman A. , Hanafy Nemany A. N. , Hafez Ezar H. 
Published: October 2023

AbstractBee pollen extract (BPE)-based polymer nanoparticles (BPENP) were fabricated using bovine serum albumin (BSA) and targeted with folic acid and were further characterized. Mice groups are: Group 1 received saline, whereas Groups 2, 3, 4, 5, and 6 received a single dose of urethane, followed by weekly injections of butylated hydroxy-toluene (BHT). After the BHT injection, the mice in Groups 3, 4, 5, and 6 received BPE, Avastin, BPENP, and BPENP + Avastin, respectively. The number and size of tumors were decreased in Group 6 compared to those in the other groups. The ratios of early and late apoptotic cells in Groups 3, 4, 5, and 6 (42.8%, 41.4%, 26.2%, and 45.4%, respectively) were higher than that in the untreated group. The PCNA-labeling indexes (LI)% in tissues and lesions from Group 6 were lower than those in the other groups; on the other hand, the Caspase-3 LI (%) was higher than those in the other groups. No significant differences in HRAS and MAPK levels were observed between Group 6 and the other groups. However, the level of Bax was significantly increased, whereas those of Bcl2 and P21 were decreased in Group 6 compared to those in Groups 4 and 5. According to the results of the current study's in vivo lung cancer mouse model, adjuvant chemotherapy given in conjunction with a polyphenolic substance derived from bee pollen significantly activates the apoptotic pathways as measured by flow cytometry, immunohistochemistry, and apoptotic genes. It also significantly reduces tumor volume and growth as measured by histopathology.
Graphical Abstract
Identification of Wolbachia new strains from Aedes aegypti mosquitoes, the vector of dengue fever in Jeddah Province
Authors: Somia E. Sharawi , Ullah Ihsan , Alyahya Hanan S. , Mahyoub Jazem A. 
Published: October 2023

AbstractWolbachia are endosymbiotic bacteria found within many arthropods, including insects. A variety of benefits are provided by these bacteria to human and insect hosts, including protection from viruses and parasites and the ability to kill males. In this study, Wolbachia was identified in Aedes aegypti present in Jeddah, Saudi Arabia. A population of mosquitoes was collected from eight different areas, processed, and tested for Wolbachia using 16 S rRNA specific to Wolbachia bacteria and Wolbachia surface protein (wsp) under optimized PCR conditions. In five ecologically diverse sites to determine Wolbachia prevalence, we identified eleven diverse novel resident Wolbachia strains within Ae. Aegypti for the first time in Jeddah, Saudi Arabia. Future studies to evaluate the possible use of Wolbachia as a control agent in Aedes sp. in Saudi Arabia are necessary. Wolbachia prevalence rates and strain characterization through Sanger sequencing with multilocus sequence typing (MLST) and phylogenetic analysis revealed significant diversity. In developing biocontrol strategies, it is beneficial to consider the implications of resident Wolbachia strains.
Metagenomic analysis of microbiological changes on the ocular surface of diabetic children and adolescents with a dry eye
Authors: Chen Zhangling , Xiao Ying , Jia Yan , Lin Qiurong , Qian Yu , Cui Lipu , Xiang Zhaoyu , Li Mingfang , Yang Chenhao , Zou Haidong 
Published: October 2023

Abstract
Background
Microbiome changes on the ocular surface may cause dry eyes. A metagenome assay was used to compare the microbiome composition and function of the ocular surface between diabetic children and adolescents with dry eye, diabetic children and adolescents without dry eye, and normal children.

Materials and methods
Twenty children and adolescents aged 8 to 16 with diabetes were selected from the Shanghai Children and Adolescent Diabetes Eye Study. Ten healthy children and adolescents belonging to the same age group were selected from the outpatient clinic during the same period. The participants were classified into the dry eye group (DM-DE group, n = 10), the non-dry eye group (DM-NDE group, n = 10) and the normal group (NDM group, n = 10). A conjunctival sac swab was collected for metagenomic sequencing, and the relationship between the microbiome composition and functional gene differences on the ocular surface with dry eye was studied.

Results
The classification composition and metabolic function of the microorganisms on the ocular surface of children in the 3 groups were analyzed. It was found that children’s ocular microbiota was composed of bacteria, viruses and fungi. There were significant differences in α diversity and β diversity of microbial composition of ocular surface between DM-DE group and NDM group(P<0.05). There were significant differences in α and β diversity of metabolic pathways between the two groups(P<0.05). The functional pathways of ocular surface microorganisms in diabetic children with dry eyes were mainly derived from human disease, antibiotic resistance genes, carbohydrate, coenzyme and lipid transport and metabolism-related functional genes; In normal children, the functional pathways were mainly derived from replication, recombination, repair, signal transduction and defense-related functional genes.

Conclusion
The DM-DE group have unique microbial composition and functional metabolic pathways. The dominant species and unique metabolic pathways of the ocular surface in the DM-DE group may be involved in the pathogenesis of dry eye in diabetic children.
Anti-HBc: a significant host predictor of spontaneous HBsAg seroclearance in chronic hepatitis B patients - a retrospective longitudinal study
Authors: Kan Karin , Wong Danny Ka-Ho , Hui Rex Wan-Hin , Seto Wai Kay , Yuen Man-Fung , Mak Lung-Yi 
Published: October 2023

Abstract
Background and Aim
: In chronic hepatitis B infection (CHB), seroclearance of hepatitis B surface antigen (HBsAg) is associated with favourable clinical outcomes compared to those with persistent HBsAg seropositivity, and thus considered as a desired treatment endpoint. This current study explores the possibility of serum antibody to hepatitis B core antigen (anti-HBc) as a potential predictive factor of HBsAg seroclearance.

Methods
This is a retrospective study that analyzed the plasma samples of CHB patients using the LUMIPULSE® G1200 analyzer. The longitudinal anti-HBc level between patients who subsequently achieved HBsAg seroclearance (S-losers) and those with persistent HBsAg-positivity (controls) were compared at multiple time points before the event.

Results
A total of 240 subjects (120 S-losers and 120 controls; age- and gender-matched) were included (mean age 56.42 ± 10.81, 65% male). Compared to controls, S-losers had significantly lower plasma anti-HBc levels prior to HBsAg seroclearance, with a significant trend of declining plasma anti-HBc 8–5 years prior to HBsAg seroclearance (p < 0.01), while such trend was not observed in controls. ROC curve analysis revealed that plasma anti-HBc at multiple time points before HBsAg seroclearance return AUC greater than 0.7. Plasma anti-HBc level at the cut-off value of 82.50 COI was 68.3% sensitive and 90% specific for HBsAg seroclearance within 1 year. Combining with quantitative HBsAg < 100 IU/mL, anti-HBc < 82.5 COI identified 88.2% patients who would develop HBsAg seroclearance within 1 year.

Conclusion
Plasma anti-HBc level began to decline 10 years prior to HBsAg seroclearance and can serve as a potential predictor for subsequent HBsAg seroclearance.
Influence of medical care tasks on subjective burden and gain among older adults’ family caregivers: structural equation modeling for testing the role of formal and informal support
Authors: Sugihara Yoko , Sugisawa Hidehiro 
Published: October 2023

Abstract
Background
The number of caregivers performing medical care tasks at home for older adults is expected to increase. Family caregivers, who are not healthcare professionals, are likely to find these activities difficult and burdensome. However, appropriate support may decrease the negative and increase the positive aspects of caregiving. This study investigated direct associations between caregivers providing medical care at home and their negative and positive appraisals of caregiving (burden and gain), indirect associations through healthcare professional support and informal support, and whether the associations between medical care tasks and caregivers’ appraisals of caregiving differed based on the support received.

Methods
Interview surveys were conducted in 2013, 2016, and 2019 in a Tokyo Metropolitan Area city with family caregivers of community-dwelling older adults who were certified as requiring care in Japan’s long-term care insurance system. This study analyzed the combined data from each survey (n = 983). Structural equation modeling (SEM) analysis was utilized to examine direct associations between providing medical care and caregiver appraisals and indirect relationships through healthcare professional support and informal support. The modulating effects of these forms of support on the relationship between medical care and caregiver appraisals were assessed using multigroup SEM analyses.

Results
Approximately 9% of family caregivers provided medical care at home. The results of SEM analyses, controlled for care recipients’ physical and cognitive difficulties; caregivers’ age, sex, and economic condition; and survey year, revealed no direct associations between providing medical care and caregivers’ sense of burden and gain. They also did not reveal any indirect effects through either healthcare professional support or informal support. However, the results of multigroup SEM analyses indicated that caregivers providing medical care who used home-visit services by physicians and/or nurses, compared to those who did not, tended to exhibit a greater sense of gain.

Conclusions
These results suggest that family caregivers providing medical care at home can positively change their appraisals of caregiving if they receive appropriate support. Home medical care services provided by healthcare professionals can effectively support caregivers. Developing strategies and policies to make medical care services at home more accessible to caregivers is crucial.
Correlation of balance posturographic parameters during quiet standing with the berg balance scale in patients with parkinson’s disease
Authors: Bao Wei , Tan Yuyan , Yang Ying , Chen Kai , Liu Jun 
Published: October 2023

Abstract
Background
Parkinson’s disease (PD) is often clinically associated with posture instability and more easily falling. The Berg balance scale is a clinical indicator commonly used to subjectively evaluate a patient’s balance ability. Meanwhile, computerized force platforms have been used in research on postural control. The various parameters obtained from posturography are interpreted to assess balance ability. The present study aims to explore the correlations between posturographic variables and the BBS, and furthermore to efficiently evaluate postural instability and fall risk of early and moderate PD patients.

Methods
A total of 46 PD patients were involved in the experiment. Patients were asked to perform BBS tests and force platform tests under eye open (EO) and eye closed (EC) conditions. The recorded COP signal was analyzed with the time domain statistical method, the frequency domain method of Power Spectral Density (PSD), and structural methods of Stabilogram Diffusion Analysis (SDA), Sway Density Plot (SDP) to retrieve different posturographic variables. The correlation between posturographic variables under EO and EC conditions with BBS was compared statistically. The significantly correlated posturographic parameters were then applied to analyze posturographic differences between different groups: faller vs. non-faller (patients with/without a history of falls in the past 12 months).

Results
Among the different posturographic parameters, the prediction ellipse area, the slope of the regression line at a high-frequency band of PSD in the medial-lateral (ML) direction, the crossover point of the regression lines of SDA in the anterior-posterior (AP) direction, and the distance between successive peaks of SDP had significant correlations with BBS. These selected BBS-related parameters also showed significant differences between faller and non-faller. The selected posturographic parameters can be used as effective indicators to evaluate the balance ability of Parkinson’s disease patients.
An endometrium of type C along with an endometrial thickness of < 8 mm are risk factors for ectopic pregnancy after stimulated cycles with fresh embryo transfer
Authors: Zhao Ying , Xu Aizhuang , Liu Dong’e , Liu Nenghui , Li Yumei , Yao Zhongyuan , Tian Fen , Tang Hongying , Li Yanping 
Published: October 2023

Abstract
Background
The study investigated whether specific ultrasonographically observed endometrial features (including endometrium type and thickness) were linked to ectopic pregnancy after stimulated cycles with fresh embryo transfer.

Method
Of 6246 pregnancy cycles after fresh embryo transfer, 6076 resulted in intrauterine pregnancy and 170 in ectopic pregnancy. The primary outcome of the study was ectopic pregnancy, with the main variables being endometrium type and endometrial thickness. Univariate and subsequent multiple-stepwise logistic regression analyses were used to identify the risk factors of ectopic pregnancy.

Results
1. Compared with patients with an endometrial thickness ≥ 8 mm, the adjusted odds ratio for those with an endometrial thickness < 8 mm was 3.368 (P < 0.001). The adjusted odds ratio for women with a type-C endometrium was 1.897 (P = 0.019) compared with non-type C. 2. A larger dose of gonadotropin used during controlled ovarian hyperstimulation was a protective factor against ectopic pregnancy (P = 0.008). 3. The GnRH antagonist protocol (P = 0.007) was a risk factor for ectopic pregnancy, compared with the use of GnRH agonists.

Conclusion
(1) An endometrial thickness < 8 mm coupled with a type C endometrium significantly increased the risk of ectopic pregnancy after fresh embryo transfer. (2) A thin endometrial thickness and a type C endometrium could be further related to an abnormal endometrial receptivity/peristaltic wave. (3) Patients at a high risk of ectopic pregnancy should therefore be given special attention, with early diagnosis during the peri-transplantation period may assist in the prevention of ectopic pregnancy.
Epigenomic perturbation of novel EGFR enhancers reduces the proliferative and invasive capacity of glioblastoma and increases sensitivity to temozolomide
Authors: Vincent Craig A. , Nissen Itzel , Dakhel Soran , Hörnblad Andreas , Remeseiro Silvia 
Published: October 2023

Abstract
Background
Glioblastoma (GB) is the most aggressive of all primary brain tumours and due to its highly invasive nature, surgical resection is nearly impossible. Patients typically rely on radiotherapy with concurrent temozolomide (TMZ) treatment and face a median survival of ~ 14 months. Alterations in the Epidermal Growth Factor Receptor gene (EGFR) are common in GB tumours, but therapies targeting EGFR have not shown significant clinical efficacy.

Methods
Here, we investigated the influence of the EGFR regulatory genome on GB cells and identified novel EGFR enhancers located near the GB-associated SNP rs723527. We used CRISPR/Cas9-based approaches to target the EGFR enhancer regions, generating multiple modified GB cell lines, which enabled us to study the functional response to enhancer perturbation.

Results
Epigenomic perturbation of the EGFR regulatory region decreases EGFR expression and reduces the proliferative and invasive capacity of glioblastoma cells, which also undergo a metabolic reprogramming in favour of mitochondrial respiration and present increased apoptosis. Moreover, EGFR enhancer-perturbation increases the sensitivity of GB cells to TMZ, the first-choice chemotherapeutic agent to treat glioblastoma.

Conclusions
Our findings demonstrate how epigenomic perturbation of EGFR enhancers can ameliorate the aggressiveness of glioblastoma cells and enhance the efficacy of TMZ treatment. This study demonstrates how CRISPR/Cas9-based perturbation of enhancers can be used to modulate the expression of key cancer genes, which can help improve the effectiveness of existing cancer treatments and potentially the prognosis of difficult-to-treat cancers such as glioblastoma.
Phosphorylation of EZH2 differs HER2-positive breast cancer invasiveness in a site-specific manner
Authors: Yu Feng , Li Lili , Zhang Mengwen , Sun Shanshan 
Published: October 2023

AbstractHER2-positive breast cancer (BC) invasiveness and drug-resistance issue is the critical treatment obstacle recently. We investigated the total and phosphorylated status EZH2 expression in database and BC tissue microarray. We demonstrated for the first time that EZH2 is distributed both in cytoplasm and nucleus of breast cancer cells in a phosphorylation site-specific manner. High expressed-EZH2 cases more frequently had an advanced clinical stage (lymph node metastasis) and aggressive features than EZH2-low cases, potentially indicating the high risk of HER2-positive BC (p < 0.05). Notably, highly expressed phosphorylated EZH2 is differently located in cytoplasm or nucleus in a site-specific manner in breast cancer cells. Nucleus-located pEZH2-S21 is expressed in invasive and lymph node metastatic HER2-positive BC cases (p = 0.144, p = 0.001). Cytoplasmic pEZH2-T487 is correlated with HER2 positive status (p = 0.014).In conclusion, high expression of nucleus-located EZH2 might be a predictor of invasive BC. Activation of phosphorylated EZH2-S21 site in nucleus would be a potential predictor of HER2-positve BC and poor efficacy of HER2-target therapy. These results point to a PRC2-independent non-epigenetic mechanism and therapeutic strategy of EZH2 in HER2-positive BC.
Prescription drugs with potential for misuse in Irish prisons: analysis of national prison prescribing trends, by gender and history of opioid use disorder, 2012 to 2020
Authors: Durand Louise , Keenan Eamon , O’Reilly Deirdre , Bennett Kathleen , O’Hara Andy , Cousins Gráinne 
Published: October 2023

Abstract
Background
Pharmacotherapy is essential for the delivery of an equivalent standard of care in prison. Prescribing can be challenging due to the complex health needs of prisoners and the risk of misuse of prescription drugs. This study examines prescribing trends for drugs with potential for misuse (opioids, benzodiazepines, Z-drugs, and gabapentinoids) in Irish prisons and whether trends vary by gender and history of opioid use disorder (OUD).

Methods
A repeated cross-sectional study between 2012 and 2020 using electronic prescribing records from the Irish Prison Services, covering all prisons in the Republic of Ireland was carried out. Prescribing rates per 1,000 prison population were calculated. Negative binomial (presenting adjusted rate ratios (ARR) per year and 95% confidence intervals) and joinpoint regressions were used to estimate time trends adjusting for gender, and for gender specific analyses of prescribing trends over time by history of OUD.

Results
A total of 10,371 individuals were prescribed opioid agonist treatment (OAT), opioids, benzodiazepines, Z-drugs or gabapentinoids during study period. History of OUD was higher in women, with a median rate of 597 per 1,000 female prisoners, compared to 161 per 1,000 male prisoners. Prescribing time trends, adjusted for gender, showed prescribing rates decreased over time for prescription opioids (ARR 0.82, 95% CI 0.80–0.85), benzodiazepines (ARR 0.99, 95% CI 0.98–0.999), Z-drugs (ARR 0.90, 95% CI 0.88–0.92), but increased for gabapentinoids (ARR 1.07, 95% CI 1.05–1.08). However, prescribing rates declined for each drug class between 2019 and 2020. Women were significantly more likely to be prescribed benzodiazepines, Z-drugs and gabapentinoids relative to men. Gender-specific analyses found that men with OUD, relative to men without, were more likely to be prescribed benzodiazepines (ARR 1.49, 95% CI 1.41–1.58), Z-drugs (ARR 10.09, 95% CI 9.0-11.31), gabapentinoids (ARR 2.81, 95% CI 2.66–2.97). For women, history of OUD was associated with reduced gabapentinoid prescribing (ARR 0.33, 95% CI 0.28–0.39).

Conclusions
While the observed reductions in prescription opioid, benzodiazepine and Z-drug prescribing is consistent with guidance for safe prescribing in prisons, the increase in gabapentinoid (primarily pregabalin) prescribing and the high level of prescribing to women is concerning. Our findings suggest targeted interventions may be needed to address prescribing in women, and men with a history of OUD.
Evaluating the association of vitamin D3, parathyroid hormone, and C-reactive protein serum levels in patients with an acute psychotic episode: a cross-sectional study in tertiary centre in Iran
Authors: Arya Shahrzad , Kamyab Amirhossein , Sanatkar Seyed Amir , Pourmehdiardebili Mohammad , Ebrahimi Alireza , Kamyab Parnia , Alavi Kaveh , Zarei Zhina , Ahmadkhaniha Hamid Reza 
Published: October 2023

Abstract
Background
The high impact of vitamin D on brain development and its relationship with inflammatory markers in the clinical course of psychiatric disorders have compelled researchers to investigate the potential association between vitamin D levels, C-reactive protein (CRP) levels, and the incidence of mental disorders. In the present study, we aimed to compare the serum levels of vitamin D and its related markers, including calcium, phosphorus, and parathyroid hormone (PTH), along with CRP, in 3 groups of patients with acute psychotic episodes, including schizophrenia, bipolar disorder, and methamphetamine-induced psychosis, with a standard control group of the Iranian population.

Methods
This descriptive cross-sectional study was conducted at a psychiatric hospital in Tehran, Iran, and involved a total of 185 subjects. The subjects included four groups: acute phase of schizophrenia (n = 49), acute manic episodes of bipolar disorder (n = 43), methamphetamine-induced psychotic disorder (n = 46), and control group (n = 47). Among 138 patients in acute psychotic episodes, 33 patients were in their first episode of psychosis, while 105 patients were in acute exacerbation of their chronic psychotic disorders. The Brief Psychiatric Rating Scale (BPRS) was measured by an expert attending psychiatrist for all patients. Then, serum levels of calcium, phosphorus, parathormone, vitamin D, and CRP were assessed in all study groups.

Results
Among our 185 study subjects, it was observed that individuals with higher education levels and those who were married had a lower prevalence of mental disorders. In all patient groups, the serum levels of CRP were significantly higher, and PTH levels were significantly lower than in the control group (p < 0.001). The serum levels of calcium, phosphorus, and vitamin D were not statistically significantly different between the patient and control groups of the study. In chronic psychotic patients, CRP levels were significantly higher (p < 0.031), and vitamin D levels were significantly lower (p < 0.044) compared to first-episode psychotic patients.

Conclusion
This study suggests that CRP levels are significantly higher and PHT level is significantly lower in acute psychotic patients. Moreover, vitamin D levels were significantly lower in chronic psychotic patients compared to first-episode psychotic patients.