bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of Vonoprazan and Tegoprazan in Helicobacter pylori eradication: a comprehensive systematic review and meta-analysis of randomized controlled trials
Authors: Jin Ting , Wu Wei , Zhang Lei , Xuan Han , Zhang Haixiang , Zhong Li 
Published: January 2025

Background: Potassium-competitive acid blocker (P-CAB)-based therapies are emerging as promising alternatives for eradicating Helicobacter pylori infection. However, the comparative efficacy of P-CAB-based therapy versus proton-pump inhibitor (PPI)-based therapy in treating H. pylori infection remains uncertain. Objectives: This meta-analysis evaluated the efficacy and safety of P-CAB-based therapies, including Vonoprazan (VPZ) and Tegoprazan (TPZ), compared to PPI-based therapies for H. pylori infection. Subgroup analysis assessed the influence of drug history, experimental drug, treatment duration, combination therapies, and geographic regions on treatment outcomes. Design: Meta-analysis. Data sources and methods: Comprehensive searches were conducted in major databases, including PubMed, Embase, the Cochrane Library, and Web of Science, up to January 1, 2024. The primary outcome was the eradication rate, analyzed by intention-to-treat (ITT). Secondary outcomes included adverse events. Heterogeneity among studies was assessed using the χ2 test and the I2 test. I2 > 50% or p < 0.05 indicated significant heterogeneity. Results: The analysis totally included 28 randomized controlled trials (RCTs) comprising 37 studies and 8818 patients diagnosed with H. pylori infection. Of these, 14 RCTs, including 20 studies and 4286 patients, compared P-CAB-based therapy with 14-day bismuth-based quadruple therapy (BQT). P-CAB-based therapy exhibited superior eradication rates compared to both 14-day BQT and PPI-based therapy (ITT analysis: 87.0% vs 79.8%, risk ratio (RR) = 1.08, 95% CI: 1.04–1.12, p < 0.0001; and 85.6% vs 77.8%, RR = 1.09, 95% CI: 1.05–1.12, p < 0.00001, respectively). This enhanced efficacy was particularly pronounced in patients with clarithromycin-resistant infections (73.7% vs 41.5%, RR = 1.53, 95% CI: 1.07–2.20, p = 0.02). Subgroup analysis demonstrated higher eradication rates with P-CAB-based therapy in treatment-naïve participants, VPZ recipients, and those receiving 7- or 14-day regimens (dual, triple, or quadruple therapy). However, no significant differences were observed in treatment-experienced subgroups, TPZ recipients, or those on 10-day regimens. In addition, P-CAB-based therapy showed a lower incidence of adverse events than PPI-based treatments (RR = 0.73, 95% CI: 0.63–0.86, p < 0.0001). Conclusion: P-CAB-based therapies are more effective than traditional PPI-based treatments for eradicating H. pylori infection, with a reduced incidence of adverse events. PROSPERO registration: CRD42024503665.
Heterogeneous treatment effects of BCG vaccine on Alzheimer's disease risk
Authors: Chaudhuri Irfan , Das Sudeshna 
Published: January 2025

Background This project has investigated the role of the Bacillus Calmette-Guérin (BCG) vaccine as a potential treatment against Alzheimer's disease (AD) and related dementias (ADRD). Objective To further establish that BCG treatment results in lower risk of ADRD through novel machine learning methods and to analyze the heterogeneity of treatment effects. Methods This retrospective cohort study was conducted from May 28, 1987 to May 6, 2021, in patients who were 50 years or older and were diagnosed with non-muscle-invasive bladder cancer (NMIBC). Follow-up duration was 15-years. Machine learning algorithms using survival analysis and the random forest algorithm were the primary methods of data analysis. Results The research has found that on average, NMIBC patients who received BCG treatment had a 6.9% (95% CI: 0.43%, 13.4%) lower risk of developing ADRD compared to those who did not. Heterogeneous treatment effects were also detected for those with a history of mental health disorders and also for those with a history of respiratory diseases. Those with mental health disorders were at a 14.7% (95% CI: 0.6%, 28.9%) reduced risk of ADRD if they received BCG treatment compared to no BCG treatment. Additionally, those taking BCG with respiratory diseases increased risk of ADRD by 13.6% (95% CI: 1.1%, 26.1%) compared to those with no BCG treatment. Conclusions BCG is associated with a lower risk of ADRD through novel analysis methods and has detected heterogeneity of treatment effects. This presents BCG as a potential low-cost method, with few side-effects, to prevent ADRD.
Reliability of nociceptive monitors vs. standard practice during general anesthesia: a prospective observational study
Authors: Norbeck Daniel Widarsson , Lindgren Sophie , Wolf Axel , Jildenstål Pether 
Published: January 2025

Abstract

Background
Inadequate or excessive nociceptive control during general anesthesia can result in significant adverse outcomes. Using traditional clinical variables, such as heart rate, systolic blood pressure, and respiratory rate, to assess and manage nociceptive responses is often insufficient and could lead to overtreatment with both anesthetics and opioids. This study evaluated the feasibility and effectiveness of three nociception monitoring techniques Nociception Level Index (NOL), Skin Conductance Algesimeter (SCA) and heart rate monitoring in patients undergoing image-guided, minimally invasive abdominal interventions under general anesthesia.

Method
This prospective observational study collected data from 2022 to 2024. All patients were anesthetized according to the department’s routine, and predetermined events were recorded. Two commercially available nociception monitors, the PMD-200 from Medasense (NOL) and PainSensor from MedStorm (SCA), were used, and their data were collected along with various hemodynamic parameters. The three nociception monitoring techniques were compared during predetermined events.

Result
A total of 49 patients were included in this study. NOL and SCA demonstrated higher responsiveness than HR for all events except for skin incision. The comparison of the values above and below the threshold for each nociceptive stimulus showed significance for all measurements using the SCA and NOL. However, using HR as a surrogate for nociception with a threshold of a 10% increase from baseline, the difference was significant only at skin incision. There was no variation in the peak values attributable to differences in patients’ age. Weight was a significant predictor of the peak NOL values.

Conclusion
NOL and SCA demonstrated superior sensitivity and responsiveness to nociceptive stimuli compared to HR, effectively detecting significant changes in nociceptive thresholds across various stimuli, although responses during skin incision showed no such advantage.

Trial registration
Clinical trial - NCT05218551.
Association of frailty with physical activity behaviour and well-being in older employees: moderated mediation by functional difficulty
Authors: Danquah Emelia , Asiamah Nestor , Jnr Reginald Arthur-Mensah , Chan Alex Sui Wing , Khan Hafiz T. A. 
Published: January 2025

Abstract

Background
Many studies have highlighted the association between frailty, physical activity behaviour (PAB), and well-being, but no study has investigated a potential moderated mediating role of functional difficulty in this relationship. This association may not be the same between different income levels. This study, therefore, assessed the above moderated mediation between low- and higher-income samples.

Methods
This research employed a cross-sectional design in accordance with established research-reporting guidelines. The study population comprised two distinct Ghanaian samples, with N = 942 individuals in the low-income group and N = 600 individuals in the higher income group. Data analysis was carried out using Hayes's Process model through structural equation modelling, with additional sensitivity analyses performed through hierarchical linear regression.

Results
Frailty had a direct negative effect and an indirect negative effect (through functional difficulty) on well-being in both samples. A partial mediation of functional difficulty was found in the relationship between frailty and well-being in both samples. We also found evidence of a moderated mediation by functional difficulty in both samples; however, this effect was stronger in the higher-income sample.

Conclusion
Older employees with frailty are less likely to report lower functional difficulty and well-being at higher PAB. Our results suggest a need for workplace programmes aimed at encouraging PAB. It also reinforces the importance of individuals performing and maintaining PAB.
Use of erectile dysfunction treatments after prostate cancer treatment and their perceived impact on men’s sex life: an analysis of patient reported outcome survey data
Authors: Charlick Megan , Tiruye Tenaw , Ettridge Kerry , O’Callaghan Michael , Jay Alex , Beckmann Kerri 
Published: January 2025

Abstract

Background
Although sexual dysfunction is a common treatment side-effect affecting men’s quality of life, many prostate cancer patients do not receive or seek out treatments for erectile dysfunction (ED). The aims of this study are to investigate the extent and patterns of use of ED treatments and their perceived impact at different times following prostate cancer treatment.

Methods
This retrospective cohort study included all men on the South Australian prostate cancer registry who completed one or more Patient Reported Outcome Measures (PROMs) survey from 2016 to 2023 (n = 5561). Outcomes included self-reported use of ED treatment (oral medications, intra-cavernosal injections (ICI) and vacuum pumps) and their impact men’s sex life at various time points after treatment. The type and timing of ED treatments used was analysed descriptively. Sociodemographic and clinical characteristics associated with utilisation and self-reported satisfaction were examined using multivariable mixed-effects binomial logistic regression.

Results
Post-treatment use of ED treatments did not exceed 43% at any timepoint, with utilisation rates decreasing over time. Oral medications were most frequently used, while vacuum pump and ICI use was limited. Oral medications were more likely to be used at three-months (odds ratio [OR] = 2.48; 95% confidence interval [95%CI] = 1.88–3.27) and six-months (OR = 2.10; 95%CI = 1.63–2.27) than at 12-months post-treatment, and among men from higher socioeconomic areas (OR = 2.41; 95%CI = 1.47–3.93, highest vs. lowest quintile), and following prostatectomy (OR = 4.37; 95%CI = 2.92–6.42), and less likely among older men (OR = 0.08; 95%CI = 0.05–0.13, < 60yrs vs. 70-79yrs). Men were more likely to report an improved sex life with oral medication use at two-years (OR = 3.79; 95%CI = 1.69–8.47) and five-years (OR = 3.07; 95%CI = 1.51–6.25) post-treatment compared with 12-months or if they were socioeconomically advantaged (OR = 3.22; 95%CI = 1.30–7.96, highest vs. lowest quintile).

Conclusions
A substantial proportion of Australian men do not access or continue to use ED treatments after prostate cancer treatment, with many users reporting only modest effects on their sex life. There is a need to improve access to and maintenance of ED treatments following prostate cancer treatment.
Heterozygous pathogenic STT3A variation leads to dominant congenital glycosylation disorders and functional validation in zebrafish
Authors: Meng Linxue , Fang Zhixu , Jiang Li , Zheng Yinglan , Hong Siqi , Deng Yu , Xie Lingling 
Published: January 2025

Abstract

Background
Congenital disorders of glycosylation are a rare group of disorders characterized by impaired glycosylation, wherein STT3A encodes the catalytic subunit of the oligosaccharyltransferase complex, which is crucial for protein N-glycosylation. Previous studies have reported that STT3A-CDG is caused by autosomal recessive inheritance. However, in this study, we propose that STT3A-CDG can be pathogenic through autosomal dominant inheritance.

Methods
The variant was identified via trio whole-exome sequencing. We constructed wild-type and variant plasmids, transfected them into HEK293T cells and detected the expression levels of the STT3A protein. We performed CRISPR-Cas9 to establish heterozygous knockdown zebrafish to validate the functional implications of autosomal dominant inheritance of STT3A in pathogenesis.

Results
The patient presented with developmental delay, distinctive facial features, short stature, and abnormal discharges. The heterozygous pathogenic missense variant (NM_001278503.2: c.499G > T, NP_001265432.1:p. Asp167Tyr) was identified, and the Western blot results revealed a significant decrease in protein levels. Heterozygous knockdown zebrafish exhibit phenotypes similar to those of patients, including craniofacial dysmorphology (increased eye distance, increased Basihyal’s length, increased Ceratohyal’s angle), skeletal abnormalities (reduced number of mineralized bones), developmental delay (reduced adaptability under light‒dark stimuli suggesting abnormal locomotion, orientation, and social behavior), and electrophysiological abnormalities.

Conclusion
We report a proband with a dominant congenital glycosylation disorder caused by heterozygous pathogenic STT3A variation, which is a new inheritance pattern of STT3A. Our report expands the known phenotype of dominant STT3A-CDGs. Furthermore, we provide in vivo validation through the establishment of a heterozygous knockdown zebrafish model for stt3a and strengthened the compelling evidence for dominant STT3A-related pathogenesis.
Hallucinations and disturbed behaviour in the critically ill: incidence, patient characteristics, associations, trajectory, and outcomes
Authors: Niccol Thomas , Young Marcus , Holmes Natasha E. , Kishore Kartik , Amjad Sobia , Gaca Michele , Bellomo Rinaldo , Serpa Neto Ary 
Published: January 2025

Abstract

Purpose
To use natural language processing (NLP) to study the incidence, characteristics, trajectory, associations, and outcomes of hallucinations and disturbed behaviour in intensive care unit (ICU) patients.

Methods
We used NLP to scan clinical progress notes of a large cohort of ICU patients to detect words indicating that a patient had experienced hallucinations. We also used NLP to detected disturbed behaviour during ICU stay. Moreover, we studied the use of antipsychotic medications in a nested cohort. Finally, we obtained the demographics, trajectory, associations, and outcome of these patients.

Results
We conducted a non-interventional, observational study of 7525 patients. We found that 625 (8.31%) had experienced hallucinations. Among these, 623 (99.7%) also had NLP-diagnosed behavioural disturbance (NLP-Dx-BD). In contrast, in patients without hallucinations, only 3274 (47.4%) were NLP-Dx-BD positive. Among the 2904 nested cohort patients with electronic medications data, 252 (8.7%) experienced hallucinations. Of these, 60 (23.8%) received medications compared with 147 (5.5%) (p < 0.001) patients without hallucinations. There was no difference on outcomes in patients with or without hallucination.

Conclusions
Hallucinations affect one in 12 ICU patients and are strongly associated with disturbed behaviour, and the use of antipsychotic medications. Hallucinations may represent another phenotype of critical illness associated neurocognitive dysfunction and require a dedicated research program.
Spray vaccination with a safe and bivalent H9N2 recombinant chimeric NDV vector vaccine elicits complete protection against NDV and H9N2 AIV challenge
Authors: Wang Xiaoquan , Dai Jing , Yang Wenhao , Yao Yao , Zhang Jin , Liu Kaituo , Lu Xiaolong , Gao Ruyi , Chen Yu , Hu Jiao , Gu Min , Hu Shunlin , Liu Xiufan , Liu Xiaowen 
Published: January 2025

Abstract
Newcastle disease virus (NDV) and H9N2 avian influenza virus (AIV) represent significant pathogenic risks to the poultry industry, leading to considerable economic losses. Vaccination is a widely used preventive measure against these pathogens, yet the lack of a live bivalent vaccine targeting NDV and H9N2 AIV imposes a heavy vaccination burden. Previously, we constructed a genotype-matched chimeric NDV vector, LX-OAI4S, in which the genotype I NDV backbone was replaced with the ectodomain of haemagglutinin-neuraminidase (HN) and modified using the attenuated F gene from the genotype VII vaccine strain A-VII. Based on the LX-OAI4S vector, we successfully generated three H9N2 recombinant viruses: LX-OAI4S-NPU-HA, LX-OAI4S-MU-HA, and LX-OAI4S-HNU-HA. These recombinants incorporated the H9N2 HA gene, flanked by untranslated regions (UTRs) from the NP, M, or HN gene of the NDV LX strain, inserted between the P and M genes of LX-OAI4S. The vaccine candidate LX-OAI4S-NPU-HA induced a more robust immune response in chickens against H9N2 AIV and NDV than the other two recombinants. This response effectively protects against virus shedding and lethal virus challenge. Furthermore, spray vaccination with LX-OAI4S-NPU-HA showed protective efficacy against H9N2 AIV and NDV. This study offers a promising strategy for comprehensive protection in regions threatened by H9N2 AIV and NDV.
Lactoferrin exhibits PEDV antiviral activity by interfering with spike-heparan sulfate proteoglycans binding and activating mucosal immune response
Authors: Liu Peng , Zuo Jinjiao , Lu Hui , Zhang Bin , Wu Caihong 
Published: January 2025

Abstract
Neonatal piglets infected with Porcine Epidemic Diarrhea Virus (PEDV) experience a mortality rate of up to 90%, resulting in significant economic losses to the swine industry in China. Current strategies using specific antibodies in sow milk to prevent Porcine Epidemic Diarrhea (PED) in these piglets through specific antibodies in sow milk is unsatisfactory. Preliminary studies have shown limited success. Emerging evidence suggests that general immune factors in sow milk provide protection to neonatal piglets, particularly, lactoferrin, play a crucial role in protecting piglets by inhibiting PEDV replication. However, the precise mechanism by which lactoferrin exerts its antiviral effects remains unclear. This study sought to clarify these mechanisms through both in vitro and in vivo approaches, proposing that higher concentrations of lactoferrin lead to greater antiviral activity. It was hypothesized that lactoferrin can impede PEDV by blocking its binding to heparan sulfate proteoglycans (HSPG) on the surface of target cells, and molecular docking experiments was conducted to identify the binding sites between lactoferrin and HSPG. Additionally, the findings indicated that lactoferrin can effectively trigger the maturation of porcine dendritic cells and boosts their antigen-presenting functions, thereby improving intestinal mucosal immunity in neonatal piglets against PEDV. Overall, these findings aid to elucidate the antiviral actions and mechanisms of lactoferrin in sow colostrum, offering new insights for the effective prevention and control of PED in neonatal piglets.
Determination of present-day crustal deformation along the Kenyan rift system using InSAR
Authors: Kirui Pius Kipng’etich , Riedel Bjorn , Gerke Markus 
Published: January 2025

Abstract
The Kenyan rift system is prone to deformation due to various geological processes and human activities, such as overexploitation of groundwater and exploitation of geothermal energy. Crustal deformation monitoring is essential for understanding the geodynamics of the rift and assessing potential hazards as the rift passes through densely populated areas. However, retrieving InSAR displacement measurements along the Kenya rift system is challenging due to the high variability in tropospheric delay caused by its location in the tropics and the significant topographic variations along the rift. Here, we leverage Sentinel-1 data to analyze both local and large-scale deformation in the rift using multi-temporal InSAR processing with an improved tropospheric correction method, which we previously proposed with a modification on variance covariance modeling. We provide evidence for the previously reported ground displacement of 5

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7.5 cm southwest of the Suswa volcano as being a misidentification of a tropospheric delay, that was dominant on March 27, 2018. Moreover, we observe episodic ground displacement at Suswa and Longonot, attributable to magma movement. Our results indicate that Suswa experienced a 9 cm movement towards the satellite line of sight between 2018-2020, while Longonot moved 4 cm towards satellite line of sight between 2016-2018 and also underwent 3 cm displacement away from the satellite line of sight between 2019-2021. In addition, we observe land subsidence associated with geothermal exploitation in the range of 1

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3.6 cm/yr in Olkaria as well as in multiple locations in Nairobi at a rate of up to 6 cm/yr, primarily attributed to groundwater overexploitation. Moreover, we detect undocumented ground displacement at the Chalbi salt flat and along the Elgeiyo escarpment, at rates of up to 4.8 cm/yr and 5.7 cm/yr, respectively. Long-wavelength, low-amplitude deformation at the Turkana depression aligned well with the current kinematics of the Kenyan rift system. We find that localized deformations, caused by magmatism and human activity, dominate the south segment of the rift, whereas large-scale low-amplitude deformations dominate the north segment. In summary, our results emphasize the importance of tropospheric delay correction in retrieving InSAR-derived displacement measurements along the Kenyan rift system.

Graphical Abstract
Survival outcome prediction of esophageal squamous cell carcinoma patients based on radiomics and mutation signature
Authors: Yan Ting , Yan Zhenpeng , Chen Guohui , Xu Songrui , Wu Chenxuan , Zhou Qichao , Wang Guolan , Li Ying , Jia Mengjiu , Zhuang Xiaofei , Yang Jie , Liu Lili , Wang Lu , Wu Qinglu , Wang Bin , Yan Tianyi 
Published: January 2025

Abstract

Background
The present study aimed to develop a nomogram model for predicting overall survival (OS) in esophageal squamous cell carcinoma (ESCC) patients.

Methods
A total of 205 patients with ESCC were enrolled and randomly divided into a training cohort (n = 153) and a test cohort (n = 52) at a ratio of 7:3. Multivariate Cox regression was used to construct the radiomics model based on CT data. The mutation signature was constructed based on whole genome sequencing data and found to be significantly associated with the prognosis of patients with ESCC. A nomogram model combining the Rad-score and mutation signature was constructed. An integrated nomogram model combining the Rad-score, mutation signature, and clinical factors was constructed.

Results
A total of 8 CT features were selected for multivariate Cox regression analysis to determine whether the Rad-score was significantly correlated with OS. The area under the curve (AUC) of the radiomics model was 0.834 (95% CI, 0.767–0.900) for the training cohort and 0.733 (95% CI, 0.574–0.892) for the test cohort. The Rad-score, S3, and S6 were used to construct an integrated RM nomogram. The predictive performance of the RM nomogram model was better than that of the radiomics model, with an AUC of 0. 830 (95% CI, 0.761–0.899) in the training cohort and 0.793 (95% CI, 0.653–0.934) in the test cohort. The Rad-score, TNM stage, lymph node metastasis status, S3, and S6 were used to construct an integrated RMC nomogram. The predictive performance of the RMC nomogram model was better than that of the radiomics model and RM nomogram model, with an AUC of 0. 862 (95% CI, 0.795–0.928) in the training cohort and 0. 837 (95% CI, 0.705–0.969) in the test cohort.

Conclusion
An integrated nomogram model combining the Rad-score, mutation signature, and clinical factors can better predict the prognosis of patients with ESCC.