bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening of Natural Compounds for CYP11A1 Stimulation Against Cell Renal Cell Carcinoma
Authors: Ong Hien Thi My , Ates Eda , Kwon Oh-Seung , Kang Min-Jung 
Published: November 2023

Abstract
Background
Renal cancer therapies are challenging owing to the extensive spreading of this cancer to other organs and its ability to pose resistance to current medications. Therefore, drugs targeting novel targets are urgently required to overcome these challenges. The cholesterol side-chain cleavage enzyme (CYP11A1) is closely associated with steroidogenesis, and its downregulation is linked to adrenal dysfunction and several types of carcinoma. We previously found that overexpression of CYP11A1 inhibited epithelial-mesenchymal transition and induced G2/M arrest in the kidney cancer Caki-1 cell line. In this context, natural compounds that exhibit potent CYP11A1 stimulation activity can be promising therpaeutic agents for kidney cancer.

Methods
We screened a panel of 1374 natural compounds in a wound-healing assay using CYP11A1-transfected Caki-1 cells. Of these, 167 promising biologically active compounds that inhibited cancer cell migration by more than 75% were selected, and their half-maximal inhibitory concentrations (IC50) were determined. The IC50 of 159 compounds was determined and 38 compounds with IC50 values less than 50 µM were selected for further analysis. Steroid hormones (cholesterol and pregnenolone) levels in cells treated with the selected compounds were quantitated using LC–MS/MS to determine their effect on CYP11A1 activity. Western blotting for CYP11A1, autophagy signaling proteins, and ferroptosis regulators were performed to ivestigate the mechanisms underlying the action of the selected compounds.

Results
We screened five promising natural lead compounds that inhibited cancer cell proliferation after three screening steps. The IC50 of these compounds was determined to be between 5.9 and 14.6 μM. These candidate compounds increased the expression of CYP11A1 and suppressed cholesterol levels while increasing pregnenolone levels, which is consistent with the activation of CYP11A1. Our results showed that CYP11A1 activation inhibited the migration of cancer cells, promoted ferroptosis, and triggered autophagy signaling.

Conclusions
This study indicates that the CYP11A1-overexpressing Caki-1 cell line is useful for screening drugs against kidney cancer. The two selected compounds could be utilized as lead compounds for anticancer drug discovery, and specifically for the development of antirenal cancer medication.
Genetic insights into the dissolution of dioecy in diploid persimmon Diospyros oleifera Cheng
Authors: Sun Peng , Nishiyama Soichiro , Li Huawei , Mai Yini , Han Weijuan , Suo Yujing , Liang Chengzhi , Du Huilong , Diao Songfeng , Wang Yiru , Yuan Jiaying , Zhang Yue , Tao Ryutaro , Li Fangdong , Fu Jianmin 
Published: November 2023

Abstract
Background
Dioecy, a sexual system of single-sexual (gynoecious/androecious) individuals, is rare in flowering plants. This rarity may be a result of the frequent transition from dioecy into systems with co-sexual individuals.

Results
In this study, co-sexual expression (monoecy and hermaphroditic development), previously thought to be polyploid-specific in Diospyros species, was identified in the diploid D. oleifeara historically. We characterized potential genetic mechanisms that underlie the dissolution of dioecy to monoecy and andro(gyno)monoecy, based on multiscale genome-wide investigations of 150 accessions of Diospyros oleifera. We found all co-sexual plants, including monoecious and andro(gyno)monoecious individuals, possessed the male determinant gene OGI, implying the presence of genetic factors controlling gynoecia development in genetically male D. oleifera. Importantly, discrepancies in the OGI/MeGI module were found in diploid monoecious D. oleifera compared with polyploid monoecious D. kaki, including no Kali insertion on the promoter of OGI, no different abundance of smRNAs targeting MeGI (a counterpart of OGI), and no different expression of MeGI between female and male floral buds. On the contrary, in both single- and co-sexual plants, female function was expressed in the presence of a genome-wide decrease in methylation levels, along with sexually distinct regulatory networks of smRNAs and their targets. Furthermore, a genome-wide association study (GWAS) identified a genomic region and a DUF247 gene cluster strongly associated with the monoecious phenotype and several regions that may contribute to andromonoecy.

Conclusions
Collectively, our findings demonstrate stable breakdown of the dioecious system in D. oleifera, presumably also a result of genomic features of the Y-linked region.
Whole-genome resequencing and transcriptome analyses of four generation mutants to reveal spur-type and skin-color related genes in apple (Malus domestica Borkh. Cv. Red delicious)
Authors: Ren Jiaxuan , Li Wenfang , Guo Zhigang , Ma Zonghuan , Wan Dongshi , Lu Shixiong , Guo Lili , Gou Huimin , Chen Baihong , Mao Juan 
Published: November 2023

Abstract
Background
Bud sport is a kind of somatic mutation that usually occurred in apple. ‘Red Delicious’ is considered to be a special plant material of bud sport, whereas the genetic basis of plant mutants is still unknown. In this study, we used whole-genome resequencing and transcriptome sequencing to identify genes related to spur-type and skin-color in the ‘Red Delicious’ (G0) and its four generation mutants including ‘Starking Red’ (G1), ‘Starkrimson’ (G2), ‘Campbell Redchief’ (G3) and ‘Vallee Spur’ (G4).

Results
The number of single nucleotide polymorphisms (SNPs), insertions and deletions (InDels) and structural variations (SVs) were decreased in four generation mutants compared to G0, and the number of unique SNPs and InDels were over 9-fold and 4-fold higher in G1 versus (vs.) G2 and G2 vs. G3, respectively. Chromosomes 2, 5, 11 and 15 carried the most SNPs, InDels and SVs, while chromosomes 1 and 6 carried the least. Meanwhile, we identified 4,356 variation genes by whole-genome resequencing and transcriptome, and obtained 13 and 16 differentially expressed genes (DEGs) related to spur-type and skin-color by gene expression levels. Among them, DELLA and 4CL7 were the potential genes that regulate the difference of spur-type and skin-color characters, respectively.

Conclusions
Our study identified potential genes associated with spur-type and skin-color differences in ‘Red Delicious’ and its four generation mutants, which provides a theoretical foundation for the mechanism of the apple bud sport.
Egg consumption and risk of cardiovascular disease: a PERSIAN cohort-based study
Authors: Mohseni Golsa khalatbari , Mohammadi Saeideh , Aghakhaninejad Zohreh , Tajadod Shirin , Abbasi Khadijeh , Askarpour Seyed Ali , Salimi Zahra , Shafaei Kachaei Hanieh , Rajabi Harsini Asma , Alami Farkhondeh , Bagheri Seyedeh Elaheh , Mosavi Jarrahi Seyed Alireza , Gohari Ali , Khoshdooz Sara , Doaei Saeid , Kooshki Akram , Gholamalizadeh Maryam 
Published: November 2023

Abstract
Background
Cardiovascular diseases (CVDs) are one of the main causes of death worldwide. Data on the effect of eggs consumption on the risk of CVDs are still unreliable. Therefore, this study aimed to investigate the association between CVDs and the consumption of eggs.

Methods
In this case-control study, the required data were extracted from the Prospective Epidemiologic Research Studies in Iran (PERSIAN) cohort in Sabzevar, Iran. A total of 4241 adults participated including 1535 patients with CVDs as the case group and 2706 healthy people as controls. Egg consumption was assessed using a valid food frequency questionnaire (FFQ).

Results
A significant association was observed between eggs consumption and stroke after adjustment for physical activity, body mass index (BMI), smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), using alcohol, lipid profile, diabetes, and the intake of energy, lipid, protein, carbohydrate, and cholestrol (OR:1.007, 95% CI:1.001–1.013, P = 0.03). No association was found between egg consumption with hypertension, cardiac ischemia, and myocardial infarction.

Conclusions
There was a significant association between the consumption of eggs and stroke. However, more studies are needed to examine the effect of eggs on CVDs.
Relationship between obesity indicators and hypertension–diabetes comorbidity in an elderly population: a retrospective cohort study
Authors: Li Haojie , Shi Zhan , Chen Xuejiao , Wang Junjie , Ding Jiacheng , Geng Shuoji , Sheng Xinyuan , Shi Songhe 
Published: November 2023

Abstract
Background
The prevalence of obesity, hypertension and diabetes is increasing. Hypertension and diabetes are common complications. Additionally, obesity and hypertension–diabetes comorbidity (HDC) are both closely related to insulin resistance. The aim of this study was to determine the association of obesity indicators with HDC in elderly individuals.

Methods
This retrospective cohort study included 74,955 subjects aged ≥ 60 years living in Xinzheng, Henan Province, from January 2011 to December 2019. The data were collected from the annual health examination dataset. Cox proportional hazard regression models and competing-risk survival regression models were used to examine the relationships between the three indicators and HDC risk.

Results
After 346,504 person-years of follow-up, HDC developed in 9,647 subjects. After further adjustments for confounders and death competing risks, compared with a body mass index (BMI) of 18.5–23.9 kg/m2, the fully adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of BMI < 18.5, 24–27.9 and ≥ 28 kg/m2 for HDC morbidity were 0.651(0.538,0.788),1.00,1.396(1.336,1.459) and 1.769(1.666,1.878), respectively. Moreover, participants with abdominal obesity measured via waist circumference (WC) or waist-to-height ratio (WtHR) had a higher risk of HDC (HR:1.513; 95% CI: 1.45,1.578 and HR:1.412;95% CI: 1.353,1.473), respectively, than participants with low WC or with low WtHR. In the joint analyses, the highest risk was observed in participants who were overweight and who had central obesity (HR: 1.721; 95% CI: 1.635, 1.811) compared with the nonoverweight and noncentral obesity groups.

Conclusions
Increased BMI, WC and WtHR were associated with an increased risk of HDC. There was an additive interaction between general body adiposity (as measured via BMI) and central obesity (as measured via WC and WtHR) for HDC. Therefore, reasonable control of BMI, WC and WtHR may be an effective measure to prevent HDC among elderly individuals.
Cognitive decline as the main manifestation of diabetic striatal disease but without involuntary movements: a case report
Authors: Li He , Cheng YiRan , Tang Wei , Hu YiBin , Jia GeHui , Wu Tong , Wang KangFeng 
Published: November 2023

AbstractDiabetic striatopathy (DS) is a rare central nervous system complication of diabetes mellitus, characterized mainly by non-ketotic hyperglycemia and lateralized involuntary movements. Patients with diabetic striatopathy manifested solely by subacute cognitive decline were rarely reported. In this paper, we report a patient with DS who presented solely with subacute cognitive decline without involuntary movements, and cranial CT showed bilateral high density in the basal ganglia. In contrast, SWI showed microhemorrhages in the right caudate nucleus head. After one week of treatment, including glycemic control, the patient showed significant improvement in cognitive function, while a repeat cranial CT showed improved hyperdensity in the right basal ganglia region. 1 month later, at telephone follow-up, the patient’s symptoms did not recur.
A national perspective on exposure to essential surgical procedures among medical trainees in Nigeria: a cross-sectional survey and recommendations
Authors: KingPriest Paul Tunde , Alayande Barnabas Tobi , Clement Emmanuel Walong , Muhammed Mustapha , Egbiri Joy Ohejem , Shanabo Miracle , Osayande Etinosa Kevin , Atunrase Abiodun Ayomide , Abubakar Jamiu Israel , Eze Daniel Chukwuma , Adekoya Stephen , Chiroma Gideon Bulus , Aikhuomogbe Onosegbe Moses , Gaila Fatima Shuwa , Yaga Dennis , Thomas Nomsu Noble , Chukwunta Chukwudi Anthony , Hey Matthew T. , Forbes Callum , Riviello Robert R. , Ismaila Bashiru O. 
Published: November 2023

Abstract
Background
In sub-Saharan Africa, recent graduates from medical school provide more direct surgical and procedural care to patients than their counterparts from the Global North. Nigeria has no nationally representative data on the procedures performed by trainees before graduation from medical school and their confidence in performing these procedures upon graduation has also not been evaluated.

Methods
We performed an internet-based, cross-sectional survey of recent medical school graduates from 15 accredited Federal, State, and private Nigerian medical schools spanning six geopolitical zones. Essential surgical procedures, bedside interventions and three Bellwether procedures were incorporated into the survey. Self-reported confidence immediately after graduation was calculated and compared using cumulative confidence scores with subgroup analysis of results by type and location of institution. Qualitative analysis of free text recommendations by participants was performed using the constant comparative method in grounded theory.

Results
Four hundred ninety-nine recent graduates from 6 geopolitical zones participated, representing 15 out of a total of 44 medical schools in Nigeria. Male to female ratio was 2:1, and most respondents (59%) graduated from Federal institutions. Students had greatest practical mean exposure to bedside procedures like intravenous access and passing urethral foley catheters and were most confident performing these. Less than 23% had performed over 10 of any of the assessed procedures.
They had least exposures to chest tube insertion (0.24/person), caesarean Sect. (0.12/person), and laparotomy (0.09/person). Recent graduates from Federal institutions had less procedural exposure in urethral catheterization (p < 0.001), reduction (p = 0.035), and debridement (p < 0.035).
Respondents that studied in the underserved North-East and North-West performed the highest median number of procedures prior to graduation. Cumulative confidence scores were low across all graduates (maximum 25/60), but highest in graduates from Northern Nigeria and private institutions. Graduates recommended prioritizing medical students over senior trainees, using simulation-based training and constructive individualized non-toxic feedback from faculty.

Conclusion
Nigerian medical students have poor exposure to procedures and low confidence in performing basic procedures after graduation. More attention should be placed on training for essential surgeries and procedures in medical schools.
How initial policy responses to COVID-19 contributed to shaping dying at home preferences and care provision: key informant perspectives from Canada
Authors: Cherba Maria , Funk Laura , Scott Erin , Salman Bora , Rounce Andrea , Mackenzie Corey , Stajduhar Kelli , Dujela Carren , Krawczyk Marian , Cohen S. Robin 
Published: November 2023

Abstract
Objectives
In response to COVID-19’s first wave, provincial governments rapidly implemented several public health directives, including isolation measures and care facility visitor restrictions, which profoundly affected healthcare delivery at the end of life and dying experiences and perceptions. The objective of this study was to identify implications of early policy changes for dying at home.

Methods
Analysis of interviews with 29 key informants with expertise in the policy and practice context of dying at home and care for those dying at home was conducted as part of a larger mixed-methods study on dying at home in Canada.

Results
Initial pandemic policy responses, especially visitor restrictions and limitations to home care services, shaped dying at home in relation to three themes: (1) increasing preferences and demand for, yet constrained system ability to support dying at home; (2) reinforcing and illuminating systemic reliance on and need for family/friend caregivers and community organizations, while constraining their abilities to help people die at home; and (3) illuminating challenges in developing and implementing policy changes during a pandemic, including equity-related implications.

Conclusion
This study contributes to broader understanding of the multifaceted impacts of COVID-19 policy responses in various areas within Canadian healthcare systems. Implications for healthcare delivery and policy development include (1) recognizing the role of family/friend caregivers and community organizations in end-of-life care, (2) recognizing health inequities at the end of life, and (3) considering possible changes in future end-of-life preferences and public attitudes about dying at home and responsibility for end-of-life care.
Implementing PCR testing in general practice—a qualitative study using normalization process theory
Authors: Shahrzad Sinead , Balasubramaniam Kirubakaran , Kousgaard Marius Brostrøm , Thilsing Trine , Søndergaard Jens , Overbeck Gritt 
Published: November 2023

Abstract
Background
The COVID-19 pandemic brought attention to a need for rapid testing of large populations. Experiences from community-based testing settings show that there can be workload difficulties, logistical challenges and socioeconomic downsides to large scale Polymerase Chain Reaction (PCR) testing. Alternative testing arenas have therefore been considered. Rapid point-of-care (POC) PCR test methods have since been developed and could have potential to surveille viral respiratory infections. It is, however, unknown if PCR testing can be successfully implemented routinely in general practice. The aim of this study was to assess factors that enable and inhibit the implementation of point-of-care PCR testing for acute respiratory tract infection in general practice.

Methods
Fourteen general practices in the east Zealand area in Denmark were included in the study and given access to POC PCR testing equipment during a flu season. The participating clinics were initially trained in the use of a POC PCR testing device and then spent 6 weeks testing it. We conducted qualitative interviews with general practitioners (GPs) and their staff, before and after the testing period, specifically focusing on their clinical decision-making and internal collaboration in relation to POC PCR testing. We used normalization process theory to design the interview guides and to analyze the data.

Results
Professionals reported no clinical need for a POC PCR testing device in a non-pandemic clinical setting. Results were delivered faster, but this was only timesaving for the patient and not the GP, who had to perform more tasks.

Conclusion
In its current form, the added diagnostic value of using POC PCR testing in general practice was not sufficient for the professionals to justify the increased work connected to the usage of the diagnostic procedure in daily practice.

Trial registration
n/a.
Multi-classification model incorporating radiomics and clinic-radiological features for predicting invasiveness and differentiation of pulmonary adenocarcinoma nodules
Authors: Sun Haitao , Zhang Chunling , Ouyang Aimei , Dai Zhengjun , Song Peiji , Yao Jian 
Published: November 2023

Abstract
Purpose
To develop a comprehensive multi-classification model that combines radiomics and clinic-radiological features to accurately predict the invasiveness and differentiation of pulmonary adenocarcinoma nodules.

Methods
A retrospective analysis was conducted on a cohort comprising 500 patients diagnosed with lung adenocarcinoma between January 2020 and December 2022. The dataset included preoperative CT images and histological reports of adenocarcinoma in situ (AIS, n = 97), minimally invasive adenocarcinoma (MIA, n = 139), and invasive adenocarcinoma (IAC, n = 264) with well-differentiated (WIAC, n = 99), moderately differentiated (MIAC, n = 84), and poorly differentiated IAC (PIAC, n = 81). The patients were classified into two groups (IAC and non-IAC) for binary classification and further divided into three and five groups for multi-classification. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO) algorithm to identify the most informative radiomics and clinic-radiological features. Eight machine learning (ML) models were developed using these features, and their performance was evaluated using accuracy (ACC) and the area under the receiver-operating characteristic curve (AUC).

Results
The combined model, utilizing the support vector machine (SVM) algorithm, demonstrated improved performance in the testing cohort, achieving an AUC of 0.942 and an ACC of 0.894 for the two-classification task. For the three- and five-classification tasks, the combined model employing the one versus one strategy of SVM (SVM-OVO) outperformed other models, with ACC values of 0.767 and 0.607, respectively. The AUC values for histological subtypes ranged from 0.787 to 0.929 in the testing cohort, while the Macro-AUC and Micro-AUC of the multi-classification models ranged from 0.858 to 0.896.

Conclusions
A multi-classification radiomics model combined with clinic-radiological features, using the SVM-OVO algorithm, holds promise for accurately predicting the histological characteristics of pulmonary adenocarcinoma nodules, which contributes to personalized treatment strategies for patients with lung adenocarcinoma.
The role of extracellular vesicles in circulating tumor cell-mediated distant metastasis
Authors: Guo Siyin , Huang Jing , Li Genpeng , Chen Wenjie , Li Zhihui , Lei Jianyong 
Published: November 2023

AbstractCurrent research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor metastasis. Primary tumors are shed and released into the bloodstream to form CTCs that are referred to as seeds to colonize and grow in soil-like distant target organs, while EVs of tumor and nontumor origin act as fertilizers in the process of tumor metastasis. There is no previous text that provides a comprehensive review of the role of EVs on CTCs during tumor metastasis. In this paper, we reviewed the mechanisms of EVs on CTCs during tumor metastasis, including the ability of EVs to enhance the shedding of CTCs, protect CTCs in circulation and determine the direction of CTC metastasis, thus affecting the distant metastasis of tumors.
A step change model analysis of the establishment of pill testing in one Australian jurisdiction
Authors: Caldicott David , Makkai Toni , McLeod Malcolm , Tzanetis Stephanie , Vumbaca Gino 
Published: November 2023

AbstractThis paper applies the theory of change model (Kotter in Harv Bus Rev 2:59–67, 1995; Moore et al. in Viet Nam J Public Health 1(1):66–75, 2013) to describe the pathway that lead to Australia’s first pill testing/drug checking services in Canberra, in the Australian Capital Territory. The paper takes each step of the model and illustrates the key activities that largely occurred over an approximately 24 month period resulting in the service being operational on 29 April 2018. The paper demonstrates that leadership, advocacy and activism are key components, alongside evidence, to bringing about public policy change. It provides a unique insight to the extensive efforts undertaken to achieving the first legally sanctioned pill testing at festivals in Australia and provides a positive case study for those seeking to introduce contested harm reduction services in the drug and alcohol field.