bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1−/− rats
Authors: Lechner Sarah A. , Barnett David G. S. , Gammie Stephen C. , Kelm-Nelson Cynthia A. 
Published: March 2024

Abstract
Background
Parkinson disease (PD) is the fastest growing neurodegenerative disease. The molecular pathology of PD in the prodromal phase is poorly understood; as such, there are no specific prognostic or diagnostic tests. A validated Pink1 genetic knockout rat was used to model early-onset and progressive PD. Male Pink1−/− rats exhibit progressive declines in ultrasonic vocalizations as well as hindlimb and forelimb motor deficits by mid-to-late adulthood. Previous RNA-sequencing work identified upregulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. The purpose of this study was to identify gene pathways within the whole blood of young Pink1−/− rats (3 months of age) and to link gene expression to early acoustical changes. To accomplish this, limb motor testing (open field and cylinder tests) and ultrasonic vocalization data were collected, immediately followed by the collection of whole blood and RNA extraction. Illumina® Total RNA-Seq TruSeq platform was used to profile differential expression of genes. Statistically significant genes were identified and Weighted Gene Co-expression Network Analysis was used to construct co-expression networks and modules from the whole blood gene expression dataset as well as the open field, cylinder, and USV acoustical dataset. ENRICHR was used to identify the top up-regulated biological pathways.

Results
The data suggest that inflammation and interferon signaling upregulation in the whole blood is present during early PD. We also identified genes involved in the dysregulation of ribosomal protein and RNA processing gene expression as well as prion protein gene expression.

Conclusions
These data identified several potential blood biomarkers and pathways that may be linked to anxiety and vocalization acoustic parameters and are key candidates for future drug-repurposing work and comparison to human datasets.
Non-alcoholic fatty liver disease in Tanzania: prevalence, determinants, and diagnostic performance of triglycerides-glucose index and triglycerides-glucose index –body mass index compared to the hepatic ultrasound in overweight and obese individuals
Authors: Kilonzo Semvua B. , Kamala Eliud , Jaka Hyasinta , Ngoya Patrick 
Published: March 2024

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD), which is closely associated with metabolic syndrome (MetS), is rarely reported in Tanzania, where MetS is prevalent. The purpose of this study was to determine the prevalence and associated factors of this condition in overweight and obese individuals and to correlate standard ultrasound diagnosis with triglyceride-glucose index (TyG) and TyG-body mass index (TyG-BMI).

Methods
A cross-sectional analysis was performed in 181 adult outpatients attending a general medical clinic. The presence of fatty liver was detected by ultrasound. Demographic, clinical, and laboratory data were collected and analyzed using STATA 15. To compare categorical variables, a chi-square test was employed, while a Student’s t-test was used to compare continuous variables. Additionally, a multivariate regression analysis was conducted to identify the determinants of NAFLD. A significance level was set at p < 0.05. The discriminatory power of TyG and TyG-BMI for diagnosing NAFLD was evaluated using Receiver Operating Characteristic (ROC) Curve analysis and the Area Under the ROC Curve (AUC) was reported.

Results
The overall prevalence of NAFLD was 30.4% (55/181). The prevalence’s of NAFLD in patients with class III obesity, class II obesity, class I obesity and overweight were 50.0% (12/24),, 38% (19/50), 23.7% (18/76), and 19.5% (6/31),respectively. NAFLD was strongly predicted by hyperuricemia (≥ 360 μmol/L) (p = 0.04) and TyG ≥ 8.99 (p = 0.003). The best cut-off values of TyG and TyG-BMI to predict NAFLD were 8.99 [AUC 0.735; sensitivity 70.9%, specificity 79.3%] and 312 [AUC 0.711; sensitivity 60% and specificity 75.4%] respectively.

Conclusions
The prevalence of NAFLD is high among people with overweight and obesity in Tanzania. We did not find sufficient evidence to recommend the use of TyG and TyG-BMI as surrogates for hepatic ultrasound in detecting NAFLD, and further evaluation is recommended.
Comparison of prognostic outcomes between endoscopic submucosal dissection and surgical treatment for early gastric cancer: a retrospective cohort study
Authors: Zhang Yifan , Shi Fangzhen , Fan Yuxiang , Liu Gang , Xia Chengkai , Wang Haodong 
Published: March 2024

Abstract
Background and aim
The optimal management strategy for early gastric cancer (EGC) a topic of contention. This study aims to compare the prognostic outcomes of endoscopic submucosal dissection (ESD) and surgical treatment in patients diagnosed with EGC.

Methods
In thisretrospective cohort study, we analyzed data from539 patients diagnosed with EGC between January 2012 and December 2020 from two centers. We compared Clinicopathological features, procedure-related complications, recurrence rate, overall survival, and disease specific survival between the 262 patients who underwent ESD and the 277 patients who underwent surgical treatment. ESD procedures were conducted using a dual knife by experienced endoscopists, while surgical treatments included laparoscopic or open gastrectomy. Regular ollow-up examinations were conducted post-treatment.

Results
The two groups exhibited comparable baseline characteristics. Multivariable Cox regression analysis identified vascular invasion as a risk factor for worse recurrence-free survival (RFS), and overall survival (OS) in patients with early gastric cancer. The ESD group experienced fewer overall postoperative complications compared to the surgical treatment group. Kaplan-Meier curves demonstrated no significant differences in recurrence rate or overall survival between the two groups.

Conclusions
Both ESD and surgical treatment emerged as safe and effective approaches for managing EGC. The choice of treatment should be tailored to individual patient factors. ESD can be considered an alternative treatment option for selected patients who are not suitable candidates for surgery. Further studies are warranted to determine the long-term outcomes of ESD and surgical treatment for EGC.
Development of a multidisciplinary medication management program in nursing homes: protocol for a randomized controlled trial
Authors: Lee Hye Jun , Jang Sunmee , Lee Ju-Yeun , Ah Young-Mi , Lee Mi-Kyung , Jang Suhyun , An Sena , Kim Jung-Ha 
Published: March 2024

Abstract
Background
Polypharmacy and the use of potentially inappropriate medications are common among nursing home residents and are associated with negative outcomes. Although deprescribing has been proposed as a way to curtail these problems, the best way to implement multidisciplinary comprehensive medication review and deprescribing and its real impact in specific high-risk populations, such as nursing home residents, is still unclear. This multicenter randomized controlled clinical trial aims to assess the effects of a multidisciplinary mediation management program on medication use and health problems.

Methods
A total of 1,672 residents aged ≥ 65 years from 22 nursing homes in South Korea who meet the targeted criteria, such as the use of ≥ 10 medications, are eligible to participate. The experimental group will receive a comprehensive medication review, deprescription, and multidisciplinary case conference with the help of platform. Outcomes will be measured at baseline, at the end of the intervention, as well as at 3, 6, 9, and 12 months after the end of the intervention. The primary endpoints will be the rate of adverse drug events, number of potentially inappropriate medications/potentially inappropriate medication users/two or more central nervous system drug/ central nervous system drug users, delirium, emergency department visits, hospitalization, and falls. The secondary endpoint will be the number of medications taken and polypharmacy users.

Discussion
Our trial design is unique in that it aims to introduce a structured operationalized clinical program focused on reducing polypharmacy and potentially inappropriate medications in a nursing home setting with large samples.

Trial registration
Ethical approval was granted by the public institutional review board of the Ministry of Health and Welfare (2022-1092-009). The study is also registered with the Clinical Research Information Service (Identifier: KCT0008157, Development and evaluation of a multidisciplinary medication management program in long-term care facility residents Status: Approved First Submitted Date: 2023/01/18 Registered Date: 2023/02/03 Last Updated Date: 2023/01/18 (nih.go.kr) https://cris.nih.go.kr/), which includes all items from the World Health Organization Trial Registration Dataset.
The RdRp genotyping of SARS-CoV-2 isolated from patients with different clinical spectrum of COVID-19
Authors: Majchrzak Michał , Madej Łukasz , Łysek-Gładysińska Małgorzata , Zarębska-Michaluk Dorota , Zegadło Katarzyna , Dziuba Anna , Nogal-Nowak Katarzyna , Kondziołka Wioleta , Sufin Iwona , Myszona-Tarnowska Mieczysława , Jaśkowski Mateusz , Kędzierski Mateusz , Maciukajć Jadwiga , Matykiewicz Jarosław , Głuszek Stanisław , Adamus-Białek Wioletta 
Published: March 2024

Abstract
Background
The evolution of SARS-CoV-2 has been observed from the very beginning of the fight against COVID-19, some mutations are indicators of potentially dangerous variants of the virus. However, there is no clear association between the genetic variants of SARS-CoV-2 and the severity of COVID-19. We aimed to analyze the genetic variability of RdRp in correlation with different courses of COVID-19.

Results
The prospective study included 77 samples of SARS-CoV-2 isolated from outpatients (1st degree of severity) and hospitalized patients (2nd, 3rd and 4th degree of severity). The retrospective analyses included 15,898,266 cases of SARS-CoV-2 genome sequences deposited in the GISAID repository. Single-nucleotide variants were identified based on the four sequenced amplified fragments of SARS-CoV-2. The analysis of the results was performed using appropriate statistical methods, with p < 0.05, considered statistically significant. Additionally, logistic regression analysis was performed to predict the strongest determinants of the observed relationships. The number of mutations was positively correlated with the severity of the COVID-19, and older male patients. We detected four mutations that significantly increased the risk of hospitalization of COVID-19 patients (14676C > T, 14697C > T, 15096 T > C, and 15279C > T), while the 15240C > T mutation was common among strains isolated from outpatients. The selected mutations were searched worldwide in the GISAID database, their presence was correlated with the severity of COVID-19.

Conclusion
Identified mutations have the potential to be used to assess the increased risk of hospitalization in COVID-19 positive patients. Experimental studies and extensive epidemiological data are needed to investigate the association between individual mutations and the severity of COVID-19.
Comparison of therapeutic effects between big-bubble deep anterior lamellar keratoplasty and penetrating keratoplasty for medically unresponsive Acanthamoeba keratitis
Authors: Qi Xiaolin , Mao Huilin , Liu Jinhui , Dong Yanling , Du Man , Liu Ting , Zhang Ting , Lu Xiuhai , Gao Hua 
Published: March 2024

Abstract
Purpose
To compare the outcomes of big-bubble deep anterior lamellar keratoplasty (BB-DALK) and penetrating keratoplasty (PKP) in the management of medically unresponsive Acanthamoeba keratitis (AK).

Methods
This retrospective study included 27 eyes of BB-DALK and 24 eyes of PKP from a tertiary ophthalmology care centre. Glucocorticoid eye drops were subsequently added to the treatment plan 2 months postoperatively based on the evaluation using confocal laser scanning microscopy. The clinical presentations, best-corrected visual acuity (BCVA), postoperative refractive outcomes, graft survival, and Acanthamoeba recurrence were analyzed.

Results
The AK patients included in the study were in stage 2 or stage 3, and the percentage of patients in stage 3 was higher in the PKP group (P = 0.003). Clinical presentations were mainly corneal ulcers and ring infiltrates, and endothelial plaques, hypopyon, uveitis and glaucoma were more common in the PKP group (P = 0.007). The BCVA and the graft survival rate showed no statistically significant differences between the two groups at 1 year after surgery. However, 3 years postoperatively, the BCVA of 0.71 ± 0.64 logMAR, the graft survival rate of 89.5%, and the endothelial cell density of 1899 ± 125 cells per square millimeter in the BB-DALK group were significantly better than those of the PKP group (P = 0.010, 0.046, and 0.032, respectively). 3 eyes (11.1%) in the BB-DALK group and 2 eyes (8.3%) in the PKP group experienced Acanthamoeba recurrence, but the rates showed no statistically significant difference between the two groups (P = 1.000). In the PKP group, immune rejection and elevated intraocular pressure were observed in 5 and 6 eyes, respectively.

Conclusion
Corneal transplantation is recommended for AK patients unresponsive to antiamoebic agents. The visual acuity and graft survival can be maintained after BB-DALK surgery. Acanthamoeba recurrence is not related to the surgical approach performed, whereas complete dissection of the infected corneal stroma and delayed prescribing of glucocorticoid eye drops were important to prevent recurrence.
Causal effects of gut microbiome on HIV infection: a two-sample mendelian randomization analysis
Authors: Li Kangjie , Zhang Cong , Deng Jielian , Zeng Haijiao , Zhang Yuan , Lai Guichuan , Zhong Xiaoni , Xie Biao 
Published: March 2024

Abstract
Background
The causal association between gut microbiome and HIV infection remains to be elucidated. We conducted a two-sample mendelian randomization analysis to estimate the causality between gut microbiome and HIV infection.

Methods
Publicly released genome-wide association studies summary data were collected to perform the mendelian analysis. The GWAS summary data of gut microbiome was retrieved from the MiBioGen consortium, which contains 18 340 samples from 24 cohorts. GWAS summary data of HIV infection was collected from the R5 release of FinnGen consortium, including 357 HIV infected cases and 218 435 controls. The SNPs were selected as instrumental variables according to our selection rules. And SNPs with a F-statistics less than ten were regarded as weak instrumental variables and excluded. Mendelian randomization analysis was conducted by five methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. The Cochran’s Q test and MR-Egger intercept test were performed to identify heterogeneity and pleiotropy. Leave-one-out analysis were used to test the sensitivity of the results.

Results
Fifteen gut microbiota taxa showed causal effects on HIV infection according to the MR methods. Four taxa were observed to increase the risk of HIV infection, including Ruminococcaceae (OR: 2.468[1.043, 5.842], P: 0.039), RuminococcaceaeUCG005 (OR: 2.051[1.048, 4.011], P: 0.036), Subdoligranulum (OR: 3.957[1.762, 8.887], P < 0.001) and Victivallis (OR: 1.605[1.012, 2.547], P=0.044). Erysipelotrichaceae was protective factor of HIV infection (OR: 0.278[0.106, 0.731], P < 0.001) and Methanobrevibacter was also found to be associated with reduced risk of HIV infection (OR: 0.509[0.265, 0.980], P=0.043). Horizontal pleiotropy was found for Fusicatenibacter (P<0.05) according to the MR-Egger regression intercept analysis. No heterogeneity was detected.

Conclusion
Our results demonstrate significant causal effects of gut microbiome on HIV infection. These findings facilitate future studies to develop better strategies for HIV prophylaxis through gut microbiome regulation. Further explorations are also warranted to dissect the mechanism of how gut microbiome affects HIV susceptibility.
Comprehensive evaluation of serum hepatic proteins in predicting prognosis among cancer patients with cachexia: an observational cohort study
Authors: Huang Jia-Xin , Zhang Xi , Tang Meng , Zhang Qi , Deng Li , Song Chun-Hua , Li Wei , Shi Han-Ping , Cong Ming-Hua 
Published: March 2024

Abstract
Background
Hepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia.

Methods
This multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan–Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL).

Results
C-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28–1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19–1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25–1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels.

Conclusion
Low albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.
Identification of PANoptosis-related signature reveals immune infiltration characteristics and immunotherapy responses for renal cell carcinoma
Authors: Xu Yan , Hua Jingqi , Que Hongliang , Zeng Tengyue , Li Quan , Deng Junpeng , Xie Jianjun 
Published: March 2024

AbstractPANoptosis is a specific type of inflammatory programmed cell death (PCD) modality that can be involved in three key modes of cellular programmed cell death-pyroptosis, apoptosis and necroptosis. We analyzed PANoptosis activity in three common renal cell carcinoma subtypes (Clear cell renal cell carcinoma, Papillary renal cell carcinoma, and Chromophobe renal cell carcinoma) separately and constructed a new PANoptosis immunity index (PANII). In three renal cell carcinomas, we found that PANII was an effective predictor of immunotherapy efficacy in KIRC, KIRP and KICH, and the high PANII group was characterized by high immune infiltration and sensitivity to immunotherapy, while the low PANII group was prone to immune escape and immunotherapy resistance. We performed molecular docking prediction of each core protein comprising PANII and identified natural small molecule compounds with the highest affinity to target proteins. In addition, we found that down-regulation of PYCARD inhibited the proliferation and migration of renal clear cell carcinoma cells by in vitro functional assays, suggesting that PYCARD could be a novel target for renal clear cell carcinoma therapy. Our findings that the PANoptosis characterization-based index (PANII) helps to elucidate the tumor microenvironmental features of three common renal cell carcinoma subtypes and identify patient populations that will benefit from immunotherapy, providing a new tool for the clinical diagnosis and treatment of patients with intermediate- and advanced-stage renal cell carcinoma.
Assessment of prevalence and risk factors associated with Hepatitis B virus infection among blood donors in Mogadishu Somalia
Authors: Mohamud Abdirahman Khalif , Inchon Pamornsri , Suwannaporn Sirinan , Prasert Kriengkrai , Dirie Najib Isse 
Published: March 2024

Abstract
Background
The Hepatitis B virus (HBV) is transmitted through contaminated blood or bodily fluids. Globally, over 81 million blood units are donated annually, a crucial therapeutic procedure without alternatives. However, blood-borne infections, including HBV, pose a significant hurdle to safe transfusions, especially in HBV-endemic regions like Somalia with limited screening. Therefore, this study aims to estimate the prevalence of Hepatitis B virus infection and identify risk factors associated with it among blood donors in Mogadishu, Somalia.

Method
A hospital-based cross-sectional study was conducted between February and April 2023. Research tools included a 5-ml blood sample and a structured questionnaire. The presence or absence of HB markers was determined using a multi-HB rapid test and CDC’s HB marker interpretation guideline. Logistic regression was used in univariate and multivariate models to identify risk factors associated with HBV infection, with significance set at a p-value < 0.05 in the final model.

Result
A total of 494 blood donors were recruited for this study; 93.9% were male, with a mean age of 31.5 (SD = 8.11). The prevalence of Hepatitis B virus (HBV) infection among blood donors was 9.7%, with a 95% CI of 7.1–12.3. In multivariable logistic regression, those with a monthly income of less than 200 USD (AOR = 5.20, 95% CI = 1.61–16.79), those with an income between 200 and 400 (AOR = 3.59, 95% CI = 1.38–9.34), Jobless blood donors (AOR = 3.78, 95% CI = 1.17–12.20), those in business occupations (AOR = 3.35, 95% CI = 1.24–9.08), those with a history of STDs (AOR = 4.83, 95% CI = 2.03–11.50), those without a history of HB vaccine (AOR = 13.81, 95% CI = 2.46–77.41), those with a history of tooth extraction (AOR = 6.90, 95% CI = 2.66–17.88), and those who shared sharp equipment (AOR = 2.90, 95% CI = 1.07–7.82) were more likely to become infected with the Hepatitis B virus (HBV) compared to their counterparts.

Conclusion
This study highlights a high prevalence of Hepatitis B virus (HBV) infection. Implementation efforts against HBV infection should specifically focus on low-income individuals, the jobless, and donors with a history of STD to mitigate the burden of HBV infection and promote safer blood donation. In addition, discouraging the sharing of sharp equipment, improving infection control practices during tooth extraction procedures, and enhancing HB vaccination uptake, particularly among individuals lacking a history of HB vaccine, is highly recommended.