bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of pancreatic fistula on survival after upfront pancreatoduodenectomy for pancreatic ductal adenocarcinoma: multicentre retrospective study
Authors: Castanet Fanny , Dembinski Jeanne , Cabarrou Bastien , Garnier Jonathan , Laurent Christophe , Regenet Nicolas , Sa Cunha Antonio , Maulat Charlotte , Chiche Laurence , Pittau Gabriella , Carrère Nicolas , Regimbeau Jean-Marc , Turrini Olivier , Sauvanet Alain , Muscari Fabrice 
Published: October 2024

Abstract

Background
The effects of postoperative pancreatic fistula on survival rates remain controversial. The aim of the present study was to evaluate the influence of postoperative pancreatic fistula on overall survival and recurrence-free survival after upfront pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

Methods
Patients operated on between January 2007 and December 2017 at seven tertiary pancreatic centres for pancreatic ductal adenocarcinoma were included in the study. Postoperative pancreatic fistula was defined using the 2016 International Study Group on Pancreatic Surgery grading system. The impact of postoperative pancreatic fistula on overall survival, recurrence-free survival (excluding 90-day postoperative deaths) and corresponding risk factors were investigated by univariable and multivariable analyses. Comparisons between groups were made using the chi-squared or Fisher’s exact test for categorical variables and the Mann–Whitney U test for continuous variables. Odds ratios were estimated with their 95% confidence intervals. Survival rates were calculated using the Kaplan–Meier method with their 95% confidence intervals.

Results
A total of 819 patients were included between 2007 and 2017. Postoperative pancreatic fistula occurred in 14.4% (n = 118) of patients; of those, 7.8% (n = 64) and 6.6% (n = 54) accounted for grade B and grade C postoperative pancreatic fistula respectively. The 5-year overall survival was 37.0% in the non-postoperative pancreatic fistula group and 45.3% in the postoperative pancreatic fistula cohort (P = 0.127). Grade C postoperative pancreatic fistula (excluding 90-day postoperative deaths) was not a prognostic factor for overall survival. The 5-year recurrence-free survival was 26.0% for patients without postoperative pancreatic fistula and 43.7% for patients with postoperative pancreatic fistula (P = 0.003). Eight independent prognostic factors for recurrence-free survival were identified: age over 70 years, diabetes, moderate or poor tumour differentiation, T3/T4 tumour stage, lymph node positive status, resection margins R1, vascular emboli and perineural invasion.

Conclusion
This high-volume cohort showed that grade C postoperative pancreatic fistula, based on the 2016 International Study Group on Pancreatic Surgery grading system, does not impact overall or recurrence-free survival (excluding 90-day postoperative deaths).
CCL2 blockade combined with PD-1/P-selectin immunomodulators impedes breast cancer brain metastasis
Authors: Israeli Dangoor Sahar , Khoury Rami , Salomon Koren , Pozzi Sabina , Shahar Shir , Miari Adan , Leichtmann-Bardoogo Yael , Bar-Hai Neta , Frommer Neta , Yeini Eilam , Winkler Tom , Balint Lahat Nora , Kamer Iris , Hadad Ori , Laue Kathrin , Brem Henry , Hyde Thomas M , Bar Jair , Barshack Iris , Ben-David Uri , Ishay-Ronen Dana , Maoz Ben M , Satchi-Fainaro Ronit 
Published: October 2024

Abstract
Over the last two decades, the diagnosis and treatment of breast cancer patients have improved considerably. However, brain metastases remain a major clinical challenge and a leading cause of mortality. Thus, a better understanding of the pathways involved in the metastatic cascade is essential.
To this end, we have investigated the reciprocal effects of astrocytes and breast cancer cells, employing traditional 2D cell culture and our unique 3D multicellular tumouroid models.
Our findings revealed that astrocytes enhance the proliferation, migration and invasion of breast cancer cells, suggesting a supportive role for astrocytes in breast cancer outgrowth to the brain. Elucidating the key players in astrocyte-breast cancer cells crosstalk, we found that CCL2 is highly expressed in breast cancer brain metastases tissue sections from both patients and mice. Our in vitro and in vivo models further confirmed that CCL2 has a functional role in brain metastasis. Given their aggressive nature, we sought additional immune checkpoints for rationale combination therapy. Among the promising candidates were the adhesion molecule P-selectin, which we have recently shown to play a key role in the crosstalk with microglia cells and the co-inhibitory receptor PD-1, the main target of currently approved immunotherapies. Finally, combining CCL2 inhibition with immunomodulators targeting either PD-1/PD-L1 or P-selectin/P-Selectin Ligand-1 axes in our human 3D tumouroid models and in vivo presented more favourable outcomes than each monotherapy.
Taken together, we propose that CCL2-CCR2/CCR4 is a key pathway promoting breast cancer brain metastases and a promising target for an immunotherapeutic combination approach.
Cerebellar activity in hemi-parkinsonian rats during volitional gait and freezing
Authors: DeAngelo Valerie , Gehan Arianna , Paliwal Siya , Ho Katherine , Hilliard Justin D , Chiang Chia-Han , Viventi Jonathan , McConnell George C 
Published: October 2024

Abstract
Parkinson’s disease is a neurodegenerative disease characterized by gait dysfunction in the advanced stages of the disease. The unilateral 6-hydroxydopamine toxin-induced model is the most studied animal model of Parkinson’s disease, which reproduces gait dysfunction after &gt;68% dopamine loss in the substantia nigra pars compacta. The extent to which the neural activity in hemi-parkinsonian rats correlates to gait dysfunction and dopaminergic cell loss is not clear. In this article, we report the effects of unilateral dopamine depletion on cerebellar vermis activity using micro-electrocorticography during walking and freezing on a runway. Gait and neural activity were measured in 6-hydroxydopamine- and sham-lesioned rats aged between 4 and 5 months at 14, 21 and 28 days after infusion of 6-hydroxydopamine or control vehicle into the medial forebrain bundle (n = 20). Gait deficits in 6-hydroxydopamine rats were different from sham rats at 14 days (P &lt; 0.05). Gait deficits in 6-hydroxydopamine rats improved at 21 and 28 days except for run speed, which decreased at 28 days (P = 0.018). No differences in gait deficits were observed in sham-lesioned rats at any time points. Hemi-parkinsonian rats showed hyperactivity in the cerebellar vermis at 21 days (P &lt; 0.05), but not at 14 and 28 days, and the activity was reduced during freezing epochs in Lobules VIa, VIb and VIc (P &lt; 0.05). These results suggest that dopaminergic cell loss causes pathological cerebellar activity at 21 days post-lesion and suggest that compensatory mechanisms from the intact hemisphere contribute to normalized cerebellar activity at 28 days. The decrease in cerebellar oscillatory activity during freezing may be indicative of neurological changes during freezing of gait in patients with Parkinson’s disease making this region a potential location for biomarker detection. Although the unilateral 6-hydroxydopamine model presents gait deficits that parallel clinical presentations of Parkinson’s disease, further studies in animal models of bilateral dopamine loss are needed to understand the role of the cerebellar vermis in Parkinson’s disease.
Cerebellar activity in PINK1 knockout rats during volitional gait
Authors: DeAngelo Valerie , Hilliard Justin D , Chiang Chia-Han , Viventi Jonathan , McConnell George C 
Published: October 2024

Abstract
Preclinical models of Parkinson's disease are imperative to gain insight into the neural circuits that contribute to gait dysfunction in advanced stages of the disease. A PTEN-induced putative kinase 1 knockout early-onset model of Parkinson's disease may be a useful rodent model to study the effects of neurotransmitter degeneration caused by a loss of PTEN-induced putative kinase 1 function on brain activity during volitional gait. The goal of this study was to measure changes in neural activity at the cerebellar vermis at 8 months of age. It was found that gait deficits, except run speed, were not significantly different from age-matched wild-type controls, as previously reported. PTEN-induced putative kinase 1 knockout (n = 4) and wild-type (n = 4) rats were implanted with a micro-electrocorticographic array placed over cerebellar vermis Lobules VI (a–c) and VII. Local field potential recordings were obtained during volitional gait across a runway. Power spectral analysis and coherence analysis were used to quantify network oscillatory activity in frequency bands of interest. Cerebellar vermis power was hypoactive in the beta (VIb, VIc and VII) and alpha (VII) bands at cerebellar vermis Lobules VIb, VIc and VII in PTEN-induced putative kinase 1 knockout rats compared with wild-type controls during gait (P &lt; 0.05). These results suggest that gait improvement in PTEN-induced putative kinase 1 knockout rats at 8 months may be a compensatory mechanism attributed to movement corrections caused by a decreased inhibition of the alpha band of cerebellar vermis Lobule VII and beta band of Lobules VIb, VIc and VII. The PTEN-induced putative kinase 1 knockout model may be a valuable tool for understanding the circuit mechanisms underlying gait dysfunction in patients with early-onset Parkinson's disease with a functional loss of PTEN-induced putative kinase 1. Future studies investigating the cerebellar vermis as a potential biomarker and therapeutic target for the treatment of gait dysfunction in Parkinson's disease are warranted.
Cerebral hyperactivation across the Alzheimer’s disease pathological cascade
Authors: Corriveau-Lecavalier Nick , Adams Jenna N , Fischer Larissa , Molloy Eóin N , Maass Anne 
Published: October 2024

Abstract
Neuronal dysfunction in specific brain regions or across distributed brain networks is a known feature of Alzheimer’s disease. An often reported finding in the early stage of the disease is the presence of increased functional MRI (fMRI) blood oxygenation level-dependent signal under task conditions relative to cognitively normal controls, a phenomenon known as ‘hyperactivation’. However, research in the past decades yielded complex, sometimes conflicting results. The magnitude and topology of fMRI hyperactivation patterns have been found to vary across the preclinical and clinical spectrum of Alzheimer’s disease, including concomitant ‘hypoactivation’ in some cases. These incongruences are likely due to a range of factors, including the disease stage at which the cohort is examined, the brain areas or networks studied and the fMRI paradigm utilized to evoke these functional abnormalities. Additionally, a perennial question pertains to the nature of hyperactivation in the context of Alzheimer’s disease. Some propose it reflects compensatory mechanisms to sustain cognitive performance, while others suggest it is linked to the pathological disruption of a highly regulated homeostatic cycle that contributes to, or even drives, disease progression. Providing a coherent narrative for these empirical and conceptual discrepancies is paramount to develop disease models, understand the synergy between hyperactivation and the Alzheimer’s disease pathological cascade and tailor effective interventions. We first provide a comprehensive overview of functional brain changes spanning the course from normal ageing to the clinical spectrum of Alzheimer’s disease. We then highlight evidence supporting a close relationship between fMRI hyperactivation and in vivo markers of Alzheimer’s pathology. We primarily focus on task-based fMRI studies in humans, but also consider studies using different functional imaging techniques and animal models. We then discuss the potential mechanisms underlying hyperactivation in the context of Alzheimer’s disease and provide a testable framework bridging hyperactivation, ageing, cognition and the Alzheimer’s disease pathological cascade. We conclude with a discussion of future challenges and opportunities to advance our understanding of the fundamental disease mechanisms of Alzheimer’s disease, and the promising development of therapeutic interventions incorporating or aimed at hyperactivation and large-scale functional systems.
Estimating state of charge of battery in renewable energy systems: a data-driven approach with artificial neural networks
Authors: Kharseh Mohamad , Balah Mohamed , Alamara Kadhim 
Published: October 2024

Abstract
Accurately determining the state of charge is crucial for efficient battery management and reliable operation in renewable energy systems. This study presents a novel approach utilizing an artificial neural network to estimate the state of charge of a battery based on key variables such as battery voltage, charging current, load current, and temperature. A photovoltaic solar energy system was installed at the American University of Ras Al Khaimah, where a comprehensive experiment was conducted over 146 hours, resulting in the collection of 3930 high-resolution data points at 2-minute intervals. The artificial neural network model was trained on 70% of the data, while the remaining 30% was used for validation and testing. The trained model achieved a mean square error of 0.000896 and an error rate of less than 2% in the state of charge estimation. The model demonstrated excellent predictive accuracy, with a determination coefficient (R²) of 99.9%, indicating a strong correlation between the predicted and actual state of charge values. These results validate the robustness of the developed artificial neural network model and its potential for real-time state of charge estimation in renewable energy systems, providing a reliable and computationally efficient alternative to traditional state of charge estimation methods.
Diagnostic validity and solute-corrected prevalence for hyponatremia and hypernatremia among 1 813 356 admissions
Authors: Okada Akira , Yamana Hayato , Watanabe Hideaki , Manaka Katsunori , Ono Sachiko , Kurakawa Kayo Ikeda , Nishikawa Masako , Kurano Makoto , Inoue Reiko , Yasunaga Hideo , Yamauchi Toshimasa , Kadowaki Takashi , Yamaguchi Satoko , Nangaku Masaomi 
Published: October 2024

ABSTRACT

Background and hypothesis
We aimed to evaluate the diagnostic validity of the International Classification of Diseases, 10th Revision (ICD-10) codes for hyponatremia and hypernatremia, using a database containing laboratory data. We also aimed to clarify whether corrections for blood glucose, triglyceride, and total protein may affect the prevalence and the diagnostic validity.

Methods
We retrospectively identified admissions with laboratory values using a Japanese hospital-based database. We calculated the sensitivity, specificity, and positive/negative predictive values of recorded ICD-10-based diagnoses of hyponatremia (E87.1) and hypernatremia (E87.2), using serum sodium measurements during hospitalization (&lt;135 and &gt;145 mmol/l, respectively) as the reference standard. We also performed analyses with corrections of sodium concentrations for blood glucose, triglyceride, and total protein.

Results
We identified 1 813 356 hospitalizations, including 419 470 hyponatremic and 132 563 hypernatremic cases based on laboratory measurements, and 18 378 hyponatremic and 2950 hypernatremic cases based on ICD-10 codes. The sensitivity, specificity, positive predictive value, and negative predictive value of the ICD-10 codes were 4.1%, 99.9%, 92.5%, and 77.6%, respectively, for hyponatremia and 2.2%, &gt;99.9%, 96.5%, and 92.8%, respectively, for hypernatremia. Corrections for blood glucose, triglyceride, and total protein did not largely alter diagnostic values, although prevalence changed especially after corrections for blood glucose and total protein.

Conclusions
The ICD-10 diagnostic codes showed low sensitivity, high specificity, and high positive predictive value for identifying hyponatremia and hypernatremia. Corrections for glucose or total protein did not affect diagnostic values but would be necessary for accurate prevalence calculation.
Post-transplant glomerular diseases: update on pathophysiology, risk factors and management strategies
Authors: Regalia Anna , Abinti Matteo , Alfieri Carlo Maria , Campise Mariarosaria , Verdesca Simona , Zanoni Francesca , Castellano Giuseppe 
Published: October 2024

ABSTRACT
In recent years, advancements in immunosuppressive medications and post-transplant management have led to a significant decrease in acute rejection rates in renal allografts and consequent improvement in short-term graft survival. In contrast, recent data have shown an increased incidence of post-transplant glomerular diseases, which currently represent a leading cause of allograft loss. Although pathogenesis is not fully understood, growing evidence supports the role of inherited and immunological factors and has identified potential pre- and post-transplant predictors. In this review, we illustrate recent advancements in the pathogenesis of post-transplant glomerular disease and the role of risk factors and immunological triggers. In addition, we discuss potential prevention and management strategies.
Adding biomarker change information to the kidney failure risk equation improves predictive ability for dialysis dependency in eGFR &lt;30 ml/min/1.73 m2
Authors: Okada Akira , Aso Shotaro , Kurakawa Kayo Ikeda , Inoue Reiko , Watanabe Hideaki , Sasabuchi Yusuke , Yamauchi Toshimasa , Yasunaga Hideo , Kadowaki Takashi , Yamaguchi Satoko , Nangaku Masaomi 
Published: October 2024

ABSTRACT

Background
Although the kidney failure risk equation (KFRE), a well-known predictive model for predicting dialysis dependency, is useful, it remains unclear whether the addition of biomarker changes to the KFRE model in patients with an estimated glomerular filtration rate (eGFR) &lt;30 ml/min/1.73 m2 will improve its predictive value.

Methods
We retrospectively identified adults with eGFR &lt;30 ml/min/1.73 m2 without dialysis dependency, and available health checkup data for two successive years using a large Japanese claims database (DeSC, Tokyo, Japan). We dichotomized the entire population into a training set (50%) and a validation set (the other half). To assess the incremental value in the predictive ability for dialysis dependency by the addition of changes in eGFR and proteinuria, we calculated the difference in the C-statistics and net reclassification index (NRI).

Results
We identified 4499 individuals and observed 422 individuals (incidence of 45.2 per 1000 person-years) who developed dialysis dependency during the observation period (9343 person-years). Adding biomarker changes to the KFRE model improved C-statistics from 0.862 to 0.921, with an improvement of 0.060 (95% confidence intervals (CI) of 0.043–0.076, P &lt; .001). The corresponding NRI was 0.773 (95% CI: 0.637–0.908), with an NRI for events of 0.544 (95% CI of 0.415–0.672) and NRI for non-events of 0.229 (95% CI of 0.186–0.272).

Conclusions
The KFRE model was improved by incorporating yearly changes in its components. The added information may help clinicians identify high-risk individuals and improve their care.
Captivity conditions matter for the gut microbiota of an endangered obligate hibernator
Authors: van Leeuwen Pauline M L , Mastromonaco Gabriela F , Mykytczuk Nadia , Schulte-Hostedde Albrecht I 
Published: October 2024

Abstract
Conservation breeding programmes include translocations of animals across breeding facilities, both in and ex situ, and to/from their natural habitat. Newly reintroduced Vancouver Island marmots (VIMs) originating from the captive breeding programme are known to experience high winter mortality once reintroduced. Whilst high winter mortality rates amongst reintroduced VIM populations remain a concern of unknown causes, this health issue could potentially be linked to changes in gut microbiota prior to hibernation. Furthermore, captivity is known to impact the gut microbiota of mammals that could be crucial for hibernation. In this study, we explored the diversity of bacterial communities in the gut of captive marmots during the entire active season, both kept in captivity at in situ and ex situ facilities, as well as free-ranging marmots during the summer period. Gut microbial diversity was higher in marmots held in ex situ facilities, outside of their habitat range, compared to captive marmots held within their habitat range, and in the wild, and differences in composition were also observed. In the entire active season, animals kept in the ex situ facility had increased abundance in taxa known to be mucin degraders, sulphate producers and possible cross-feeders, whilst an increase in fibre degraders of in situ and free-ranging marmots is potentially linked to diet variation between facilities. These results confirm the interest to transfer animals held at zoos to an in situ facility before relocation and expand our understanding of microbiota variation according to hibernation cycles in the context of conservation biology.
Older women with non-ST-elevation acute coronary syndrome undergoing invasive or conservative management: an individual patient data meta-analysis
Authors: Rubino Francesca , Pompei Graziella , Mills Gregory B , Kotanidis Christos P , Laudani Claudio , Bendz Bjørn , Berg Erlend S , Hildick-Smith David , Hirlekar Geir , Morici Nuccia , Myat Aung , Tegn Nicolai , Sanchis Forés Juan , Savonitto Stefano , De Servi Stefano , Kunadian Vijay 
Published: October 2024

Abstract

Aims
Women and older patients are underrepresented in randomized controlled trials (RCTs) investigating treatment strategies following acute coronary syndrome. This study aims to evaluate the benefit of invasive vs. conservative strategy of older women with non-ST-elevation acute coronary syndrome (NSTEACS).

Methods and results
This analysis from an individual patient data meta-analysis included six RCTs comparing an invasive management with a conservative management in older NSTEACS patients. The primary endpoint was the composite of all-cause mortality or myocardial infarction (MI). Secondary endpoints included all-cause mortality, cardiovascular death, MI, urgent revascularization, and stroke. Follow-up time was censored at 1 year. In total, 717 women [median age 84.0 (interquartile range 81.0–87.0) years] were included. The primary endpoint occurred in 21.0% in the invasive strategy vs. 27.8% in the conservative strategy [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.52–1.13, P = 0.160 using random effect] at 1-year follow-up. The invasive management was associated with reduced risk of MI (HR 0.49, 95% CI 0.32–0.73, P &lt; 0.001) and urgent revascularization (HR 0.44, 95% CI 0.20–0.98, P = 0.045). No significant differences were identified in the risk of all-cause mortality, cardiovascular death, and stroke. Among males, there was no significant association between the treatment strategy and primary or secondary endpoints.

Conclusion
An invasive strategy compared with a conservative strategy did not reduce the composite outcome of all-cause mortality or MI in older NSTEACS women at 1-year follow-up. An invasive strategy reduced the individual risk of MI and urgent revascularization. Our results support the beneficial role of the invasive strategy in older NSTEACS women.

Registration
This meta-analysis is registered with PROSPERO (CRD42023379819).