bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dapagliflozin improves podocytes injury in diabetic nephropathy via regulating cholesterol balance through KLF5 targeting the ABCA1 signalling pathway
Authors: Sun Jingshu , Zhang Xinyu , Wang Simeng , Chen Dandan , Shu Jianqiang , Chong Nannan , Wang Qinglian , Xu Ying 
Published: February 2024

AbstractDiabetic nephropathy (DN), one of the more prevalent microvascular complications in patients diagnosed with diabetes mellitus, is attributed as the main cause of end-stage renal disease (ESRD). Lipotoxicity in podocytes caused by hyperglycemia has been recognised as a significant pathology change, resulting in the deterioration of the glomerular filtration barrier. Research has demonstrated how dapagliflozin, a kind of SGLT2i, exhibits a multifaceted and powerful protective effect in DN, entirely independent of the hypoglycemic effect, with the specific mechanism verified. In this present study, we found that dapagliflozin has the potential to alleviate apoptosis and restore cytoskeleton triggered by high glucose (HG) in vivo and in vitro. We also discovered that dapagliflozin could mitigate podocyte cholesterol accumulation by restoring the expression of ABCA1, which is the key pathway for cholesterol outflows. This research also mechanistically demonstrates that the protective effect of dapagliflozin can be mediated by KLF-5, which is the upstream transcription factor of ABCA1. Taken together, our data suggest that dapagliflozin offers significant potential in alleviating podocyte injury and cholesterol accumulation triggered by high glucose. In terms of the mechanism, we herein reveal that dapagliflozin could accelerate cholesterol efflux by restoring the expression of ABCA1, which is directly regulated by KLF-5.
Low persistence of Phytophthora ramorum (Werres, De Cock, and Man in ‘t Veld) in western France after implementation of eradication measures
Authors: Beltran Arielle , Laubray Simon , Ioos Renaud , Husson Claude , Marçais Benoit 
Published: February 2024

Abstract
Key message
Presence of Phytophthora ramorum (Werres, De Cock, and Man in ‘t Veld) in western France was studied after the detection of this invasive pathogen in 2017 in Larix kaempferi (Lamb.) and eradication of the affected stands. P. ramorum was seldom detected in the area of the outbreak in the year following eradication. However, we confirm that P. ramorum can multiply to epidemic level on chestnuts (Castanea sativa Mill.) in the absence of larch (Larix spp.). This represents the major risk in France.

Context
Phytophthora ramorum is an invasive oomycete that causes significant damage in the USA and Europe. Although the pathogen has been present in nurseries in France since 2002, the first outbreaks in forest stands were identified in 2017 in plantations of Larix kaempferi in two forests in western France (Saint-Cadou and Hanvec). In order to limit the development of the epidemic, neighboring larch stands were clear-cut.

Aim
This study investigated the presence of P. ramorum in the affected area after the eradication treatment.

Methods
Larch stands located within a 18-km radius of the reported outbreaks were investigated. We also monitored the native woody hosts present in infected clear-cut larch stands and in the vicinity of seven ornamental nurseries that had been infected by P. ramorum on several occasions in the past.

Results
Overall, a very limited presence of P. ramorum was detected in 2018–2021. Two new stands of infected L. kaempferi were found close to the main initial outbreak, in Saint-Cadou and Saint-Rivoal. The pathogen was only detected on rhododendrons and chestnut trees (Castanea sativa Mill.) in the vicinity of the outbreaks. In the Saint-Cadou state Forest, an outbreak of the disease developed in 2019–2021 on chestnut trees even though all the mature larch trees had been felled. P. ramorum was also detected near two of the formerly infected ornamental nurseries, on Castanea sativa and on rhododendrons.

Conclusion
While larches and rhododendrons are uncommon in the forests of north-western France, chestnut trees are present in 21–25% of the forest and therefore represent the major risk for the survival of P. ramorum in the region.
Time variation of high-risk groups for liver function deteriorations within fluctuating long-term liver function after hepatic radiotherapy in patients with hepatocellular carcinoma
Authors: Tsai Yu-Lun , Yu Pei-Chieh , Nien Hsin-Hua , Lu Tzu-Pin 
Published: February 2024

Abstract
Purpose
The purpose of this study is to find essential risk factors associated with liver function (LF) deteriorations within fluctuating long-term LF and their time-varying effects in patients with hepatocellular carcinoma (HCC) receiving hepatic radiotherapy and to identify high-risk groups for adverse LF deteriorations and their changes over time in facilitating the prevention of hepatic decompensation and the improvement of survival.

Materials and methods
A total of 133 HCC patients treated by hepatic radiotherapy were enrolled. A study design was conducted to convert posttreatment long-term LF with fluctuating levels over time to recurrent LF events using defined upgrades in a grading scale. The hazard ratios (HR) of pretreatment biochemical, demographic, clinical, and dosimetric factors in developing posttreatment LF events were estimated using the Cox model. Methodologies of the counting process approach, robust variance estimation, goodness-of-fit testing based on the Schoenfeld residuals, and time-dependent covariates in survival analysis were employed to handle the correlation within subjects and evaluate the time-varying effects during long-term follow-up.

Results
Baseline LF score before radiotherapy and gender were significant factors. Initial HR in developing LF events was 1.17 (95% CI 1.11–1.23; P < 0.001) for each increase of baseline LF score and kept almost constant over time (HR, 1.00; 95% CI 1.00–1.01; P = 0.065). However, no difference was observed regarding initial hazards for gender (HR, 1.00; 95% CI 0.64–1.56; P = 0.994), but the hazard for women got higher monthly over time compared with men (HR, 1.04; 95% CI 1.01–1.07; P = 0.006).

Conclusions
High-risk groups for adverse LF deteriorations after hepatic radiotherapy may change over time. Patients with poor baseline LF are vulnerable from the beginning. Women require prevention strategies and careful monitoring for deteriorations at a later stage.
Divergent maturational patterns of the infant bacterial and fungal gut microbiome in the first year of life are associated with inter-kingdom community dynamics and infant nutrition
Authors: Mercer Emily M. , Ramay Hena R. , Moossavi Shirin , Laforest-Lapointe Isabelle , Reyna Myrtha E. , Becker Allan B. , Simons Elinor , Mandhane Piush J. , Turvey Stuart E. , Moraes Theo J. , Sears Malcolm R. , Subbarao Padmaja , Azad Meghan B. , Arrieta Marie-Claire 
Published: February 2024

Abstract
Background
The gut microbiome undergoes primary ecological succession over the course of early life before achieving ecosystem stability around 3 years of age. These maturational patterns have been well-characterized for bacteria, but limited descriptions exist for other microbiota members, such as fungi. Further, our current understanding of the prevalence of different patterns of bacterial and fungal microbiome maturation and how inter-kingdom dynamics influence early-life microbiome establishment is limited.

Results
We examined individual shifts in bacterial and fungal alpha diversity from 3 to 12 months of age in 100 infants from the CHILD Cohort Study. We identified divergent patterns of gut bacterial or fungal microbiome maturation in over 40% of infants, which were characterized by differences in community composition, inter-kingdom dynamics, and microbe-derived metabolites in urine, suggestive of alterations in the timing of ecosystem transitions. Known microbiome-modifying factors, such as formula feeding and delivery by C-section, were associated with atypical bacterial, but not fungal, microbiome maturation patterns. Instead, fungal microbiome maturation was influenced by prenatal exposure to artificially sweetened beverages and the bacterial microbiome, emphasizing the importance of inter-kingdom dynamics in early-life colonization patterns.

Conclusions
These findings highlight the ecological and environmental factors underlying atypical patterns of microbiome maturation in infants, and the need to incorporate multi-kingdom and individual-level perspectives in microbiome research to improve our understandings of gut microbiome maturation patterns in early life and how they relate to host health.
Assault-related traumatic brain injury hospitalizations in Canada from 2010 to 2021: rates, trends and comorbidity
Authors: Saxena Shikha , Zutrauen Sarah , McFaull Steven R. 
Published: February 2024

Abstract
Background
Traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. TBI is often associated with other physical or psychological issues resulting in high hospitalization costs. TBI incidence and recovery can vary with the external cause being intentional or unintentional. It is important to monitor the rates of TBI hospitalizations related to different external causes. This study examined the annual rate, comorbidity and length of stay associated with assault-related TBI hospitalizations and compare it with other external causes, by age and sex in Canada from 2010 to 2021.

Methods
Discharge Abstract Database was used to extract cases of TBI (2010–2021). ICD-10-CA codes were used to classify all cases with TBI as per assault and other external causes (falls; transport; sport, physical activity and recreation; struck by). Additional variables, including age, sex, comorbidity and length of stay, were examined. Time trends were quantified using Joinpoint regression.

Results
The average annual percent increase for all TBI hospitalizations from 2010 to 2021 was not significant at 0.1%. Females accounted for 35.8% of these TBI hospitalizations. From 2010 to 2021, assault-related TBI hospitalizations showed a significant annual decline of 4.1% for males and a significant increase of 1.2% for females. Increase in TBI hospitalizations related to falls showed an average annual percent increase of 1.4% for males and 2.2% for females. A significant decrease was observed for TBI hospitalizations related to the other three (transport, SPAR and struck by) external causes for both sexes from 2010 to 2021. Infants and children under 10 years of age had higher percentages of cases with comorbidities and higher length of stay for assault-related TBI hospitalizations.

Conclusions
Assault-related TBI hospitalization rates decreased overall and among males, rates among females increased from 2010 to 2021. These results underscore the importance of targeted prevention efforts for TBI related to different external causes, age and sex, and continued surveillance to monitor the epidemiology of assault-related TBI.
The practical clinical role of machine learning models with different algorithms in predicting prostate cancer local recurrence after radical prostatectomy
Authors: Hu Chenhan , Qiao Xiaomeng , Hu Chunhong , Cao Changhao , Wang Ximing , Bao Jie 
Published: February 2024

Abstract
Background
The detection of local recurrence for prostate cancer (PCa) patients following radical prostatectomy (RP) is challenging and can influence the treatment plan. Our aim was to construct and verify machine learning models with three different algorithms based on post-operative mpMRI for predicting local recurrence of PCa after RP and explore their potential clinical value compared with the Prostate Imaging for Recurrence Reporting (PI-RR) score of expert-level radiologists.

Methods
A total of 176 patients were retrospectively enrolled and randomly divided into training (n = 123) and testing (n = 53) sets. The PI-RR assessments were performed by two expert-level radiologists with access to the operative histopathological and pre-surgical clinical results. The radiomics models to predict local recurrence were built by utilizing three different algorithms (i.e., support vector machine [SVM], linear discriminant analysis [LDA], and logistic regression-least absolute shrinkage and selection operator [LR-LASSO]). The combined model integrating radiomics features and PI-RR score was developed using the most effective classifier. The classification performances of the proposed models were assessed by receiver operating characteristic (ROC) curve analysis.

Results
There were no significant differences between the training and testing sets concerning age, prostate-specific antigen (PSA), Gleason score, T-stage, seminal vesicle invasion (SVI), perineural invasion (PNI), and positive surgical margins (PSM). The radiomics model based on LR-LASSO exhibited superior performance than other radiomics models, with an AUC of 0.858 in the testing set; the PI-RR yielded an AUC of 0.833, and there was no significant difference between the best radiomics model and the PI-RR score. The combined model achieved the best predictive performance with an AUC of 0.924, and a significant difference was observed between the combined model and PI-RR score.

Conclusions
Our radiomics model is an effective tool to predict PCa local recurrence after RP. By integrating radiomics features with the PI-RR score, our combined model exhibited significantly better predictive performance of local recurrence than expert-level radiologists’ PI-RR assessment.
How do breast cancer clinical trials approach cardiovascular safety: targeted or generalized?
Authors: Hamid Arsalan , Fonarow Gregg C. , Butler Javed , Hall Michael E. 
Published: February 2024

Abstract
Background
Different breast cancer pharmacotherapy agents cause different forms of cardiovascular toxicity. We aim to assess if breast cancer pharmacotherapy trials approach cardiovascular safety in a targeted or generalized manner when administering different agents.

Methods
We searched Embase and Medline for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion for cardiovascular conditions and cardiovascular safety assessment through cardiovascular imaging, electrocardiogram, troponin, or natriuretic peptides. Fisher’s exact test was utilized to compare reporting.

Results
Fifty breast cancer clinical trials were included in this study. Trials administering microtubule inhibitors were most likely to exclude patients with any CV condition compared with trials administering other agents (93.5% vs. 68.4%; p < 0.05), particularly coronary artery disease (77.4% vs. 36.8%; p < 0.01) but reported performing an electrocardiogram in 13 (41.9%) trials. Trials administering anti-HER 2 agents excluded all patients with at least one CV condition, particularly patients with heart failure (100.0% vs. 62.9%) and were more likely to perform echocardiograms (80.0% vs. 22.9%, p < 0.001) compared with other agents. Other agents excluded participants in a generalized manner and do not frequently perform targeted safety assessments.

Conclusions
Only trials administering microtubule inhibitors or anti-HER 2 therapy exclude patients with cardiovascular disease in a targeted approach. However, anti-HER 2 therapy trials are the only breast cancer clinical trials that perform targeted safety assessments. Breast cancer clinical trials need to develop a targeted approach to cardiovascular safety assessments to permit inclusion of high-risk participants and generate clinical trial data generalizable to patients with cardiovascular disease undergoing cancer therapy.
Forest thinning and prescribed burning treatments reduce wildfire severity and buffer the impacts of severe fire weather
Authors: Brodie Emily G. , Knapp Eric E. , Brooks Wesley R. , Drury Stacy A. , Ritchie Martin W. 
Published: February 2024

Abstract
Background
The capacity of forest fuel treatments to moderate the behavior and severity of subsequent wildfires depends on weather and fuel conditions at the time of burning. However, in-depth evaluations of how treatments perform are limited because encounters between wildfires and areas with extensive pre-fire data are rare. Here, we took advantage of a 1200-ha randomized and replicated experiment that burned almost entirely in a subsequent wildfire under a wide range of weather conditions. We compared the impacts of four fuel treatments on fire severity, including two thin-only, a thin-burn, a burn-only, and an untreated control. We evaluated four fire severity metrics—tree mortality, average bole char height, percent crown volume consumed (PCVC), and percent crown volume affected (PCVA)—and leveraged data from pre-fire surface and canopy fuels to better understand the mechanisms driving differences in wildfire severity among treatments and how they changed with fire weather.

Results
We found strong mitigating effects of treatments on fire behavior and tree mortality, despite 20 years having elapsed since mechanical thinning and 10 years since the second entry of prescribed fire. The thin-burn treatment resulted in the lowest fire severity across all four metrics and the untreated control the highest. All four fire severity metrics were positively associated with pre-fire canopy and surface fuel loads, with the exception that PCVC (a fire severity metric related to crown fire behavior) was not associated with surface fuel load. The fire weather conditions under which fuel treatment was most effective varied among fire severity metrics. Fuel treatment benefit was maximized at intermediate burning index values for tree mortality, intermediate to high burning index values for PCVA, and high burning index for bole char height and PCVC.

Conclusions
We conclude that reducing canopy bulk density via mechanical thinning treatments can help to limit crown fire behavior for 20 years or more. However, reducing surface fuels is necessary to limit scorching and the total crown impacts associated with tree mortality. Further, while fuel treatment effectiveness may decline under the most severe fire weather conditions for fire severity metrics associated with tree mortality, it is maximized under severe fire weather conditions for fire severity metrics associated with crown fire behavior (bole charring and torching). Our results provide strong evidence for the use of fuel treatments to mitigate fire behavior and resulting fire severity even under extreme fire weather conditions.
Adult attention-deficit hyperactivity disorder: time for a rethink?
Authors: Matheiken Shevonne , Erden Meriç , Krishnadas Rajeev , Pinto da Costa Mariana 
Published: February 2024

SUMMARYRecent years have seen a rise in media coverage as well as demand for specialist attention-deficit hyperactivity disorder (ADHD) assessments in adults and children. This article explores the challenges in the diagnostic process for adult ADHD, amidst much misinformation and controversy. In doing so, we look at the social model of ADHD; a glossary of terms to better understand lived experience; underdiagnosis and misdiagnosis; and the fallacy of the ‘high functioning’ label. We propose the use of co-production to bridge the gap between the medical and social models. We conclude with suggestions for future research. The article includes anonymous contributions from doctors with ADHD.
Equity Investment in Physician Practices: What's All This Brouhaha?
Authors: Pauly Mark V. , Burns Lawton Robert 
Published: February 2024

Abstract
There have been two waves of equity-based investment in physician practices. Both used a combination of public and private sources but in different mixes. The first investment wave, in the 1990s, was led by public equity and physician practice management companies, with less involvement by private equity (PE). The second investment wave followed the Affordable Care Act and was led by PE firms. It has generated concerns of wasteful spending, less cost-effective care, and initiatives harmful to patient welfare. This article compares the two waves and asks if they are parallel in important ways. It describes the similarities in the players, driving forces, acquisition dynamics, spurs to consolidation, types of equity involved, models to organize physicians, and levels of market penetration achieved. The article then tackles three unresolved issues: Does PE investment differ from other investment vehicles in concerning ways? Does PE possess capabilities that other investment vehicles lack and confer competitive advantage? Does physician practice investment offer opportunities for supernormal profits? It then discusses ongoing trends that may disrupt PE and curtail its practice investment. It concludes that past may be prologue, that is, what happened during the 1990s may well repeat, suggesting the PE threat is overblown.
Artificial Sweeteners and Pancreatic Cancer: Is Aspartame a Culprit or a Coincidence?
Authors: Han Sanghoon , Yang Jieun , Park Ji Eun , Kim Jung Ho 
Published: February 2024

doi: https://doi.org/10.12669/pjms.40.4.8490
How to cite this: Han S, Yang J, Park JE, Kim JH. Artificial Sweeteners and Pancreatic Cancer: Is Aspartame a Culprit or a Coincidence? Pak J Med Sci. 2024;40(4):790. doi: https://doi.org/10.12669/pjms.40.4.8490
Corticosteroid injection for carpal tunnel syndrome: A meta-analysis comparing ultrasound guided approach with landmark approach
Authors: Jiang Anqing , Qian Yushun , Yan Jun , Zhang Shouchun , Zhu Siqiang 
Published: February 2024

Objective: To assess and compare the clinical and functional outcomes of corticosteroid injections in patients with carpal tunnel syndrome, focusing on two different approaches: ultrasound-guided and landmark-guided.
Methods: A systematic search was conducted in PubMed, Scopus and Embase databases for relevant studies published prior to 30th April 2023. Studies that were either randomized controlled trials or had a cohort design were included. The review assessed symptom severity, functional status, electrodiagnostic parameters, complications, need for surgical intervention, visual analogue score, and grip strength. Pooled effect sizes were reported as relative risk (RR) or weighted mean difference (WMD).
Results: A total of 8 articles were included. Compared to those that received steroid injection using landmark approach, those with ultrasound guided approach had lower symptom severity scale (SSS) score on Boston Carpal Tunnel Questionnaire (BCTQ) [WMD -0.50, 95% CI: -0.94, -0.07; I2=78.0%, N=7], lower risk of “any complications” [RR 0.58, 95% CI: 0.36, 0.93; I2= 22.9%, N=3] and lower risk of need for surgical intervention [RR 0.55, 95% CI: 0.34, 0.89; I2= 3.0%, N=2]. All other parameters were similar in the two groups i.e., functional status scale (FSS) score, visual analogue score (VAS) and grip strength. The electrophysiological findings were similar in the two groups.
Conclusion: Findings suggest that ultrasound guided approach may be better than landmark guided approach especially in terms of alleviation of symptoms, reducing the risk of complications and need for surgical intervention. However, larger trials with long term follow up may provide conclusive evidence.
doi: https://doi.org/10.12669/pjms.40.4.8749
How to cite this: Jiang A, Qian Y, Yan J, Zhang S, Zhu S. Corticosteroid injection for carpal tunnel syndrome: A meta-analysis comparing ultrasound guided approach with landmark approach. Pak J Med Sci. 2024;40(4):773-778. doi: https://doi.org/10.12669/pjms.40.4.8749
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