bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analysis of a susceptibility gene (HIPP27) in the Arabidopsis thaliana-Meloidogyne incognita pathosystem by using a genome editing strategy
Authors: Dutta Tushar K. , Vashisth Neeraj , Ray Soham , Phani Victor , Chinnusamy Viswanathan , Sirohi Anil 
Published: August 2023

Abstract
Background
Plant-parasitic root-knot nematodes cause immense yield declines in crop plants that ultimately obviate global food security. They maintain an intimate relationship with their host plants and hijack the host metabolic machinery to their own advantage. The existing resistance breeding strategies utilizing RNAi and resistance (R) genes might not be particularly effective. Alternatively, knocking out the susceptibility (S) genes in crop plants appears to be a feasible approach, as the induced mutations in S genes are likely to be long-lasting and may confer broad-spectrum resistance. This could be facilitated by the use of CRISPR/Cas9-based genome editing technology that precisely edits the gene of interest using customizable guide RNAs (gRNAs) and Cas9 endonuclease.

Results
Initially, we characterized the nematode-responsive S gene HIPP27 from Arabidopsis thaliana by generating HIPP27 overexpression lines, which were inoculated with Meloidogyne incognita. Next, two gRNAs (corresponding to the HIPP27 gene) were artificially synthesized using laboratory protocols, sequentially cloned into a Cas9 editor plasmid, mobilized into Agrobacterium tumefaciens strain GV3101, and transformed into Arabidopsis plants using the floral dip method. Apart from 1–3 bp deletions and 1 bp insertions adjacent to the PAM site, a long deletion of approximately 161 bp was documented in the T0 generation. Phenotypic analysis of homozygous, ‘transgene-free’ T2 plants revealed reduced nematode infection compared to wild-type plants. Additionally, no growth impairment was observed in gene-edited plants.

Conclusion
Our results suggest that the loss of function of HIPP27 in A. thaliana by CRISPR/Cas9-induced mutagenesis can improve host resistance to M. incognita.
ST-segment elevation myocardial infarction heart of Charlotte one-year (STEMI HOC-1) study: a prospective study protocol
Authors: Badianyama Marheb , Mutyaba Arthur , Nel Samantha , Tsabedze Nqoba 
Published: August 2023

Abstract
Background
ST-segment elevation myocardial infarction (STEMI) is a clinically distinguishable yet lethal sequela of ischaemic heart disease (IHD). In sub-Saharan Africa (SSA), death due to acute STEMI is increasing. In South Africa, there is a paucity of data available on the clinical outcomes of acute STEMI within one year for individuals treated in the public healthcare sector. This study primarily seeks to determine the one-year all-cause mortality rate of acute STEMI. The study also assesses the value of serum cardiac biomarkers of myocardial damage and serum uric acid in predicting all-cause mortality in STEMI.

Methods
This is a single-centre observational prospective cohort of all consecutive individuals presenting with an acute STEMI to the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa. Research data will be sourced on admission through electronic medical records, blood laboratory results and coronary angiography reports, and at follow-up through periodic telephonic interviews and standardised echocardiograms. At least 355 eligible participants will be continuously followed over one year, and clinical outcomes will be measured 30 days, three months, six months and one year after the index hospitalisation.

Discussion
This study provides insights into the demographic, risk factors and clinical profiles of individuals with STEMI in South Africa. Its findings may improve the risk stratification, prognostication, and therapeutic management of STEMI patients in our setting. By comparing the clinical outcomes between the different coronary reperfusion strategies, our results may guide clinicians in providing better patient treatment, particularly in sub-Saharan Africa, where access to percutaneous coronary intervention may be limited. Furthermore, the study offers insights into the routine use of baseline serum uric acid as a potential low-cost prognostic biomarker of all-cause mortality in STEMI. Finally, this study’s findings may be of public health significance to local policymakers to aid in reinforcing primary prevention strategies and developing structured referral networks for timely coronary reperfusion of acute STEMI.
Laparoscopic common bile duct exploration with primary closure could be safely performed among elderly patients with choledocholithiasis
Authors: Fan Lili , Wang Yan , Wu Meilong , Wu Tianchong , Deng Lingna , Wang Yawei , Liu Linsen , An Tailai 
Published: August 2023

Abstract
Background
For patients with choledocholithiasis, laparoscopic common bile duct exploration (LCBDE) is preferred over open surgery. Whether primary closure of the common bile duct (CBD) should be performed upon completion of choledochotomy remains unclear, and the corresponding indications for primary closure of the common bile duct have yet to be fully identified. This study was performed to evaluate the safety and feasibility of primary closure of CBD among elderly patients (≥ 70 years) after LCBDE.

Methods
Patients with choledocholithiasis who had undergone LCBDE with primary closure of the CBD between July 2014 and December 2020 were retrospectively reviewed. Included patients were assigned into two groups (Group A: ≥70 years and Group B: <70 years) according to age. Group A was compared with Group B in terms of preoperative characteristics, intraoperative results and postoperative outcomes.

Results
The mean operative time for Group A was 176.59 min (± 68.950), while the mean operative time for Group B was 167.64 min (± 69.635) (P = 0.324). The mean hospital stay after surgery for Group A was 8.43 days (± 4.440), while that for Group B was 8.30 days (± 5.203) (P = 0.849). Three patients in Group A experienced bile leakage, while bile leakage occurred in 10 patients in Group B (3.8% vs. 4.5%, P = 0.781). Group A was not significantly different from Group B in terms of postoperative complications and 30-day mortality except pneumonia (P = 0.016), acute cardiovascular event (P = 0.005) and ICU observation (P = 0.037). After a median follow-up time of 60 months, 2 patients in Group A and 2 patients in Group B experienced stone recurrence (2.5% vs. 0.9%, P = 0.612). One patient in Group A experienced stenosis of the CBD, while stenosis of the CBD occurred in 5 patients in Group B (1.3% vs. 2.2%, P = 0.937).

Conclusions
Primary closure of CBD upon completion of LCBDE could be safely performed among patients ≥ 70 years.
Transitions in robust and prefrail octogenarians after 1 year: the influence of activities of daily living, social participation, and psychological resilience on the frailty state
Authors: Costenoble Axelle , Knoop Veerle , Debain Aziz , Bautmans Ivan , Van Laere Sven , Lieten Siddhartha , Rossi Gina , Verté Dominique , Gorus Ellen , De Vriendt Patricia ,   the Gerontopole Brussels Study Group, Verté Dominque , Beyer Ingo , Petrovic Mirko , De Witte Nico , Kardol Tinie , Clarys Peter , Scafoglieri Aldo , Cattrysse Eric , de Hert Paul , Jansen Bart 
Published: August 2023

Abstract
Background
Knowledge opportunities lie ahead as everyday activities, social participation, and psychological resilience might be important predictors for frailty state transitioning in the oldest old. Therefore, this article aims to examine whether changes in basic-, instrumental-, advanced- activities of daily living (b-, i-, a-ADLs), social participation, and psychological resilience predict both a transition from robustness to prefrailty or frailty and vice versa among community-dwelling octogenarians over a follow-up period of one year.

Methods
To evaluate worsened and improved frailty transitions after one year in 322 octogenarians (Mage = 83.04 ± 2.78), the variables sex, ADLs (b-ADL-DI, i-ADL-DI, a-ADL-DI as baseline and as difference after 6 months values), the CD-RISC (Connor-Davidson Resilience Scale, as baseline and as difference after 6 months), the social participation variables (total participation score, being a member, total number of memberships, level of social participation, being a board member, volunteering, and formal participation as baseline and as difference after 6 months values), were included in a logistic regression analysis.

Results
Limitations in a-ADLs at baseline (OR: 1.048, 95% confidence interval, 1.010–1.090) and an increment of limitations in a-ADLs after 6 months (OR: 1.044, 95% confidence interval, 1.007–1.085) were predictors to shift from robust to a worsened frailty state after one year follow-up. Additionally, being a woman (OR: 3.682, 95% confidence interval, 1.379–10.139) and social participation, specifically becoming a board member in 6 months (OR: 4.343, 95% confidence interval, 1.082–16.347), were protectors of robustness and thus related to an improved frailty transition after one year.

Conclusions
Encouraging healthy lifestyle behaviors to help the maintenance of ADLs, possibly leading to more social participation, could be promising in the prevention of frailty.
Impact of adenomyosis on perinatal outcomes: a large cohort study (JSOG database)
Authors: Komatsu Hiroaki , Taniguchi Fuminori , Harada Tasuku 
Published: August 2023

Abstract
Background
A previous study investigated the effect of adenomyosis on perinatal outcomes. Some studies have reported varying effect of adenomyosis on pregnancy outcomes in some patients and dependence on the degree and subtype of uterine lesions. To elucidate the impact of adenomyosis on perinatal outcomes.

Methods
This large-scale cohort study used the perinatal registry database of the Japan Society of Obstetrics and Gynecology. A dataset of 203,745 mothers who gave birth between January 2020 and December 2020 in Japan was included in the study. The participants were divided into two groups based on the presence or absence of adenomyosis. Information regarding the use of fertility treatment, delivery, obstetric complications, maternal treatments, infant, fetal appendages, obstetric history, underlying diseases, infectious diseases, use of drugs, and maternal and infant death were compared between the groups.

Results
In total, 1,204 participants had a history of adenomyosis and 151,105 did not. The adenomyosis group had higher rates of uterine rupture (0.2% vs. 0.01%, P = 0.02) and placenta accreta (2.0% vs. 0.5%, P < 0.001) than the non-adenomyosis group. A history of adenomyosis (odds ratio: 2.26; 95% confidence interval: 1.43–3.27; P < 0.001), uterine rupture (odds ratio: 3.45; 95% confidence interval: 0.89–19.65; P = 0.02), placental abruption (odds ratio: 2.11; 95% confidence interval: 1.27–3.31; P < 0.01), and fetal growth restriction (odds ratio: 2.66; 95% confidence interval: 2.00–3.48; P < 0.01) were independent risk factors for placenta accreta.

Conclusion
Adenomyosis in pregnancies is associated with an increased risk of placenta accreta, uterine rupture, placental abruption, and fetal growth restriction.

Trial registration
Institutional Review Board of Tottori University Hospital (IRB no. 21A244).
AGR2 and FOXA1 as prognostic markers in ER-positive breast cancer
Authors: Zhou Meng , Gan Xing-li , Ren Yue-xiang , Chen Qian-xin , Yang Yuan-zhong , Weng Zi-jin , Zhang Xiao-fang , Guan Jie-xia , Tang Lu-ying , Ren Ze-fang 
Published: August 2023

Abstract
Background
The prognostic role of either forkhead box A1 (FOXA1) or anterior gradient 2 (AGR2) in breast cancer has been found separately. Considering that there were interplays between them depending on ER status, we aimed to assess the statistical interaction between AGR2 and FOXA1 on breast cancer prognosis and examine the prognostic role of the combination of them by ER status.

Methods
AGR2 and FOXA1 expression in tumor tissues were evaluated with tissue microarrays by immunohistochemistry in 915 breast cancer patients with follow up data. The expression levels of these two markers were treated as binary variables, and many different cutoff values were tried for each marker. Survival and Cox proportional hazard analyses were used to evaluate the relationship between AGR2, FOXA1 and prognosis, and the statistical interaction between them on the prognosis was assessed on multiplicative scale.

Results
Statistical interaction between AGR2 and FOXA1 on the PFS was significant with all the cutoff points in ER-positive breast cancer patients but not ER-negative ones. Among ER-positive patients, the poor prognostic role of the high level of FOXA1 was significant only in patients with the low level of AGR2, and vice versa. When AGR2 and FOXA1 were considered together, patients with low levels of both markers had significantly longer PFS compared with all other groups.

Conclusions
There was a statistical interaction between AGR2 and FOXA1 on the prognosis of ER-positive breast cancer. The combination of AGR2 and FOXA1 was a more useful marker for the prognosis of ER-positive breast cancer patients.
Mechanism of prognostic marker SPOCK3 affecting malignant progression of prostate cancer and construction of prognostic model
Authors: Luo Jiawen , Lai Cong , Xu Xiaoting , Shi Juanyi , Hu Jintao , Guo Kaixuan , Mulati Yelisudan , Xiao Yunfei , Kong Degeng , Liu Cheng , Xu Kewei 
Published: August 2023

Abstract
Background
SPOCK3 is a secreted extracellular matrix proteoglycan. This study aimed to investigate the effect of SPOCK3 on the malignant progression of prostate cancer and to construct a prognostic model to predict DFS of patients with prostate cancer.

Methods
Clinical and transcriptome sequencing data for prostate cancer were download from the TCGA and GEO databases. The survival curve showed that SPOCK3 has prognostic significance. GO, KEGG, and GSEA enrichment analysis were used to investigate how SPOCK3 affects the malignant progression of prostate cancer. Based on ESTIMATE and ssGSEA, the relationship between SPOCK3 and immune cell infiltration in prostate cancer tissue was clarified. Univariate and multivariate COX regression analysis was used to identify the independent prognostic factors of prostate cancer OS and to construct a nomogram. The calibration curve and ROC curves were drawn to assess the nomogram's predictive power.

Results
The survival curve revealed that patients in the low-expression group of SPOCK3 had a poor prognosis. According to enrichment analysis, SOPCK3-related genes were enriched in collagen-containing extracellular matrix, PI3K-Akt, and MAPK signaling pathway. ESTIMATE analysis revealed that SPOCK3 expression was positively correlated with the interstitial score, immune score, and ESTIMATE score. The results of ssGSEA analysis revealed that the infiltration levels of Mast cells, NK cells, and B cells were higher in the SPOCK3 high expression group. Cox regression analysis showed that SPOCK3 expression level, T and Gleason score were independent risk factors of patient prognosis, and a nomogram was constructed. The ROC curve showed the AUCs of DFS at 2, 3, and 5 years.

Conclusion
SPOCK3 is a protective factor for DFS in prostate cancer patients. SPOCK3 is significantly associated with immune cell infiltration. The prognostic model constructed based on SPOCK3 has excellent predictive performance.
Intrinsic functional connectivity correlates of cognitive deficits involving sustained attention and executive function in bipolar disorder
Authors: Wu Yan-Kun , Su Yun-Ai , Zhu Lin-Lin , Li Ji-Tao , Li Qian , Dai You-Ran , Lin Jing-Yu , Li Ke , Si Tian-Mei 
Published: August 2023

Abstract
Background
The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further investigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the different relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs).

Methods
Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic resonance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clinical assessment. A seed-based approach was used to evaluate the intrinsic FC alterations in three core neurocognitive networks (the default mode network [DMN], the central executive network [CEN] and the salience network [SN]). Finally, we examined the relationship between FC and cognitive performance by using linear regression analyses.

Results
Decreased FC was observed within the DMN, in the DMN-SN and DMN-CEN and increased FC was observed in the SN-CEN in BD. The alteration direction of regional FC was consistent with that of FC at the brain network level. Decreased FC between the left posterior cingulate cortex and right anterior cingulate cortex was associated with longer WCST completion time in BD patients (but not in HCs).

Conclusions
These findings emphasize the dominant role of the DMN in the psychopathology of BD and provide evidence that cognitive deficits in BD may be associated with aberrant FC between the anterior and posterior DMN.
Emergency department use and geospatial variation in social determinants of health: a pilot study from South Carolina
Authors: DeMass Reid , Gupta Deeksha , Self Stella , Thomas Darin , Rudisill Caroline 
Published: August 2023

AbstractBackgroundHealth systems are increasingly addressing patients’ social determinants of health (SDoH)-related needs and investigating their effects on health resource use. SDoH needs vary geographically; however, little is known about how this geographic variation in SDoH needs impacts the relationship between SDoH needs and health resource use.MethodsThis study uses data from a SDoH survey administered to a pilot patient population in a single health system and the electronic medical records of the surveyed patients to determine if the impact of SDoH needs on emergency department use varies geospatially at the US Census block group level. A Bayesian zero-inflated negative binomial model was used to determine if emergency department visits after SDoH screening varied across block groups. Additionally, the relationships between the number of emergency department visits and the response to each SDoH screening question was assessed using Bayesian negative binomial hurdle models with spatially varying coefficients following a conditional autoregressive (CAR) model at the census block group level.ResultsStatistically important differences in emergency department visits after screening were found between block groups. Statistically important spatial variation was found in the association between patient responses to the questions concerning unhealthy home environments (e.g. mold, bugs/rodents, not enough air conditioning/heat) or domestic violence/abuse and the mean number of emergency department visits after the screen.ConclusionsNotable spatial variation was found in the relationships between screening positive for unhealthy home environments or domestic violence/abuse and emergency department use. Despite the limitation of a relatively small sample size, sensitivity analyses suggest spatially varying relationships between other SDoH-related needs and emergency department use.
Cost-effectiveness and potential budget impact of non-pharmacological interventions for early management in prehypertensive people: an economic evaluation for China
Authors: Liang Leyi , Shao Taihang , Li Hao , Zhao Mingye , Tang Wenxi 
Published: August 2023

Abstract
Background
Non-pharmacological interventions (NPIs) could be considered in the early management of prehypertensive population. This study aimed to evaluate the potential cost-effectiveness of NPIs and the budget impact of implementing NPIs on prehypertensive population in China and provide evidence of chronic disease management innovation for decision-makers.

Methods
Five NPIs including usual care, lifestyle, strengthen exercise, relaxation, and diet therapy were selected based on the practice of hypertension management in China. A nine-state Markov model was constructed to evaluate the lifetime costs and health outcomes of five NPIs and a non-intervention group from the perspective of Chinese healthcare system. The effectiveness of NPIs was obtained from a published study. Parameters including transition probabilities, costs and utilities were extracted or calculated from published literature and open-access databases. Sensitivity analyses were conducted to test the uncertainty of all parameters. The impact of duration of intervention was considered in scenario analyses. A budget impact analysis (BIA) was conducted to evaluate the total cost and the medical cost saving of a hypothetical nationwide implementation of potential cost-effective NPI in prehypertensive people. Management strategies including focusing on patients with specific ages or different CVE risk levels, and different duration of implementation were taken into consideration.

Results
Strengthen exercise was the most cost-effective intervention with a probability of 78.1% under the given WTP threshold. Our results were sensitive to the cost of interventions, and the utility of prehypertension and hypertension. The duration of implementation had limited impact on the results. BIA results showed that the program cost was hefty and far more than the medical cost saving with the course of simulation time. Applying management strategies which focused on individual characteristics could largely reduce the program cost despite it remained higher than medical cost saving.

Conclusions
Strengthen exercise was a potential NPI that can be considered in priority for early management in prehypertensive population. Although early management can acquire medical cost saving, the related program cost can be quite hefty. Precise strategies which may help reduce the cost of early management should be taken into consideration in program design.