bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute introduction of monomeric or multimeric α‐synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses
Authors: Román‐Vendrell Cristina , Wallace Jaqulin N. , Watson Aurelia Hays , Celikag Meral , Bartels Tim , Morgan Jennifer R. 
Published: November 2024

AbstractSynaptic aggregation of α‐synuclein often occurs in Parkinson's disease (PD), dementia with Lewy bodies (DLB) and other synucleinopathies and is associated with cognitive deficits and dementia. Thus, it is important to understand how accumulation of α‐synuclein affects synapse structure and function. Native, physiological α‐synuclein comprises a mixture of tetramers and related physiological oligomers (60–100 kDa) in equilibrium with monomeric α‐synuclein. We previously demonstrated that acutely increasing the levels of physiological α‐synuclein impaired intracellular synaptic vesicle trafficking and produced a pleiotropic phenotype, raising questions about which aspects of the synaptic phenotype were due to multimeric versus monomeric α‐synuclein. Here, we address this by taking advantage of the unique features of the lamprey giant reticulospinal (RS) synapse, a vertebrate synapse that is amenable to acute perturbations of presynaptic processes via microinjection of purified proteins. α‐Synuclein monomers and multimers were purified from HEK cells and separately introduced to lamprey synapses. Ultrastructural analysis revealed that both multimeric and monomeric α‐synuclein impaired intracellular vesicle trafficking, leading to a loss of synaptic vesicles and buildup of endosomes. However, while monomeric α‐synuclein additionally induced atypical fusion/fission at the active zone and impaired clathrin‐mediated endocytosis, multimeric α‐synuclein did not. Conversely, multimeric α‐synuclein led to a decrease in synaptic vesicle docking, which was not observed with monomeric α‐synuclein. These data provide further evidence that different molecular species of α‐synuclein produce distinct and complex impacts on synaptic vesicle trafficking and reveal important insights into the cell biological processes that are affected in PD and DLB.
imageKey points
α‐Synuclein accumulation at synapses is associated with cognitive decline and dementia in Parkinson's disease and other synucleinopathies.
We previously showed that acute introduction of excess human brain‐derived α‐synuclein to lamprey giant synapses caused pleiotropic phenotypes on synaptic vesicle trafficking, probably due to the mixture of molecular species of α‐synuclein.
Here, we dissected which aspects of the synaptic phenotypes were caused by monomeric (14 kDa) or multimeric (60–100 kDa) α‐synuclein by purifying each molecular species and introducing each one separately to synapses via axonal microinjection.
While monomeric α‐synuclein inhibited clathrin‐mediated synaptic vesicle endocytosis, multimeric α‐synuclein primarily impaired endosomal trafficking.
These findings reveal that different molecular species of α‐synuclein have distinct impacts on synapses, suggesting different cellular and molecular targets.
Rock glacier inventory and predictive modeling in the Mackenzie Mountains: predicting rock glacier likelihood with a generalized additive model
Authors: Thiessen Rabecca , Bonnaventure Philip P. , Lapalme Caitlin M. 
Published: November 2024

Rock glaciers have been the subject of extensive research in recent years due to their potential to serve as indicators of past and present climate conditions and their potential impacts on water resources. Location and descriptive rock glacier data within the Mackenzie Mountains were used to build a rock glacier inventory that will serve as a valuable resource for future research and monitoring efforts. Additionally, this study maps the likelihood of rock glacier presence using extracted variables in a generalized additive model (GAM). The model incorporates attribute data, including potential incoming solar radiation (PISR), topographic position index (TPI), slope, elevation, and lithology as controls for rock glacier development. Topographic data were compiled for three study regions of the Mackenzie Mountains from a 30 m digital elevation model (DEM). The analysis of the GAM showed that the most significant explanatory variables were PISR, elevation, slope, and TPI. The GAM model had an accuracy of 0.87 with a sensitivity of 0.92. This study provides important insights into the controls, distribution, and dynamics of rock glaciers in the Mackenzie Mountains, as well as both the limitations and the potential of statistical models in predicting their occurrence.
DeePathNet: A Transformer-Based Deep Learning Model Integrating Multiomic Data with Cancer Pathways
Authors: Cai Zhaoxiang , Poulos Rebecca C. , Aref Adel , Robinson Phillip J. , Reddel Roger R. , Zhong Qing 
Published: November 2024

Abstract
Multiomic data analysis incorporating machine learning has the potential to significantly improve cancer diagnosis and prognosis. Traditional machine learning methods are usually limited to omic measurements, omitting existing domain knowledge, such as the biological networks that link molecular entities in various omic data types. Here, we develop a transformer-based explainable deep learning model, DeePathNet, which integrates cancer-specific pathway information into multiomic data analysis. Using a variety of big datasets, including ProCan-DepMapSanger, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas, we demonstrate and validate that DeePathNet outperforms traditional methods for predicting drug response and classifying cancer type and subtype. Combining biomedical knowledge and state-of-the-art deep learning methods, DeePathNet enables biomarker discovery at the pathway level, maximizing the power of data-driven approaches to cancer research. DeePathNet is available on GitHub at https://github.com/CMRI-ProCan/DeePathNet.

Significance:
DeePathNet integrates cancer-specific biological pathways using transformer-based deep learning for enhanced cancer analysis. It outperforms existing models in predicting drug responses, cancer types, and subtypes. By enabling pathway-level biomarker discovery, DeePathNet represents a significant advancement in cancer research and could lead to more effective treatments.
Financial Performance among Selected Liquified Petroleum Gas (LPG) Retail Stores in Talisay City, Cebu
Authors: Romero Charlotte , Polinar Mark Anthony N. , Delantar Alexander Franco A. 
Published: November 2024

The Liquified Petroleum Gas (LPG) sector plays a noteworthy part in the local economy, supplying essential energy resources for residential and commercial use. The COVID-19 pandemic has brought massive distractions that significantly affect the financial performance of companies, regardless of the sector they belong to, and this sector is not exempted. This study examined the financial performance of these LPG retail stores in Talisay City, Cebu, to know if they recovered financially, particularly in recent economic downturns and market forces. After examining the financial data for the years 2022 and 2023 using the identified financial ratios, the authors found that all participating LPG retail stores showed a positive financial performance in terms of their net profit margin, current ratio, debt-to-equity, asset turnover, and cash flow to debt ratios. This implies that LPG retail stores operate efficiently, maintain robust profitability, manage financial obligations correctly, and ensure sufficient liquidity. Additionally, it can give owners a positive perspective on the growth and stability in Talisay City, Cebu.
A importância dos conceitos de “paisagem” para o ambientalismo brasileiro
Authors: Andrade Júnior José Roberto Porto de 
Published: November 2024

This article intends to contribute to the debate on the importance of the concepts of “landscape” for national environmentalism, especially in the context of socio-environmental collapse we are currently experiencing, marked by the intensification of the negative consequences of climate change. The discussion starts with a characterization and critical analysis of the use of the concepts of “landscape” in three fields: Ecology, Environmental Education, and Law by means of a non-systematic bibliographic review and analysis of secondary data.
From Apocalypse to Empowerment: Reframing Climate Action
Authors: Steinberg Paul F. 
Published: November 2024

Abstract
This article proposes empowerment as a new frame for analyzing, communicating, and practicing climate action. I first discuss the role of collective action frames in social movements and the limitations of the predominant apocalyptic climate narratives. I then elaborate the concept of empowerment, which has received little attention from political scientists, who have emphasized “power-over” rather than “power-to.” Empowerment has long been a focus of attention within critical social work, feminist theory, community psychology, and social movement theory. Drawing on these literatures and others, I identify three dimensions of empowerment—critical awareness, resources and opportunities, and autonomy—and consider practical steps that climate leaders can take to empower others to simultaneously pursue personal development and social transformation.
The Impact of Non-trauma Factors on Trauma Patient Mortality and Hospital Resource Utilization: Population-Based Retrospective Review
Authors: Javier Mariel , Luque Ilko , Kliewer Jaclyn , Lopez Nicole Yordan , Ritchie David , Dominguez Beatriz Cobo , Morejon Orlando 
Published: November 2024

Background The death of trauma patients with low injury severity scores (ISS) may not be fully explained by the severity of their injuries. Our objective was to evaluate preexisting conditions (PECs) that may contribute to the mortality rate of and hospital resources consumed by patients with low ISS. Methods Trauma patients with ISS <9 were selected from the National Trauma Database Bank [NTDB] [2019-21]. Bivariate and multivariate analysis identified the risk factors associated with mortality, adjusting for secondary PECs, mechanism of injury, AIS body region, vital signs, and blood transfusion. A t test was used to compare PEC status with intensive care unit (ICU) and hospital length of stay (LOS) for significant differences ( P < .05). Results 1,689,392 patients suffered mild injuries [59.1% male, mean age 45.2, 8579 expired (0.5%)]. Mortality was associated with the presence of several risk factors, especially advanced directive [OR = 9.13, P < .001], cirrhosis [OR = 8.55, P < .001], disseminated cancer [OR = 8.53, P < .001], congestive heart failure (CHF) [OR = 6.62, P < .001], chronic renal failure (CRF) [OR = 6.16, P < .001], chemotherapy for cancer [OR = 5.64, P < .001], peripheral arterial disease (PAD) [OR = 5.32, P < .001], myocardial infarction (MI) [OR = 4.96, P < .001], dementia [OR = 4.62, P < .001], and functionally dependent health [OR = 4.57, P < .001]. In addition, there was a relationship between the presence of several PECs and increased ICU and hospital LOS, especially cirrhosis, CRF, CHF, and PAD. Discussion Nontraumatic factors and preexisting conditions are associated with increased mortality and hospital resource consumption in trauma patients with a low ISS. They should be considered during clinical decision-making for these patients, who may otherwise masquerade as part of a low-risk population.
Enlarged Frontal Sinusotomy and Chronic Rhinosinusitis with Nasal Polyps: An Effective Strategy to Control the Disease
Authors: Saccardo Tommaso , Nicolas Valentine , Chebib Emilien , Manca di Villahermosa Stefano , Verillaud Benjamin , Vinciguerra Alessandro , Herman Philippe 
Published: November 2024

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with a strong impact on the quality of life (QoL) which treatment is based on local intranasal corticosteroids (ICS) and iterative courses of systemic corticosteroids (SCS) in case of relapse. When medical treatment is insufficient, surgery is indicated. We investigated the impact of enlarged frontal sinusotomies (EFS: Draf IIb or Draf III) on QoL and annual SCS consumption of patients with severe uncontrolled CRSwNP. Methods: This is a retrospective cohort study of 38 patients, who underwent EFS at Lariboisière University Hospital (CHU) in Paris, France, between 2006 and 2020. All patients were asked to complete SNOT-22 questionnaires concerning pre- and post-op status. Patients’ medical and sinus surgery history as well as the number of SCS treatments per year before and after surgery were also collected. Results: Of the 38 patients, 33 underwent a Draf III procedure and 5 a Draf IIb, with no major complications reported. Surgery resulted in a significant improvement in SNOT-22 scores (−32.7 ± 19.3, P < 0.001), with 19/22 items improving significantly. The number of annual SCS treatments decreased significantly from a mean of 4.8 ± 4.3 to 0.6 ± 1.2 ( P < 0.001). During the follow-up (mean 88 months), 95% of our patients showed a satisfying disease control and only 2 patients required revision surgery for poor disease control 5 years after EFS. Conclusion: EFS appears to be an effective and durable therapeutic option to improve the QoL of patients with severe CRSwNP and to reduce their SCS consumption without major complications.
Bivariate Generalized Exponential Distribution with Positive Probability at (X = 0, Y = 0) and Estimation of Parameters for a Particular Case
Authors: George Saju Verghese , Dixit Vaijayanti Ullas 
Published: November 2024

Kundu and Gupta, 2009, J Multivar Anal, 100, 581–593, provided a bivariate generalized exponential distribution (BVGED [Formula: see text]), which is a bivariate continuous lifetime distribution. In practice, however, sometimes both the components may fail instantaneously. Thus, we get a mixture bivariate distribution with positive probability at instantaneous failure of each component. The main aim of this article is to define a BVGED with positive probability at instantaneous failure of each component (BVGEDP [Formula: see text]), where PX=0P(X = 0) and P(Y = 0) is a function of parameter [Formula: see text]. It is observed that the joint probability density function and the cumulative distribution function can be expressed in compact forms. Several properties of the distribution have been discussed. For a particular case (BVGEDP ([Formula: see text] 1, 1, 1)), moment type estimators are obtained which are in closed form and maximum likelihood estimators of parameters ([Formula: see text]) are obtained using an iterative procedure. Also, their finite sample and asymptotic properties are discussed using simulation. A final section presents an application to a real data set on which the proposed BVGEDP ([Formula: see text], 1, 1, 1) distribution is fitted. AMS Subject Classification: 62E99
Topical Therapies for Management of Olfactory Dysfunction in Chronic Rhinosinusitis with Nasal Polyps: Steroid-Eluting Stents
Authors: Zhang Zhidi , Zuo Qiang , Du Yali , Jiang Hailing , Wang Jiayue , Ma Furong , Zhang Yinghong 
Published: November 2024

Objectives: Steroid-eluting stent implantation after endoscopic sinus surgery (ESS) effectively alleviates postoperative symptoms and polyp recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, the efficacy of steroid-eluting stents for the treatment of olfactory dysfunction in CRSwNP and the influencing factors therein have not been studied. Methods: Fifty-nine patients with CRSwNP with olfactory dysfunction from Peking University Third Hospital who were hospitalized for ESS were recruited and randomly divided into a stent group (n = 30) and a control group (n = 29), and were assessed for symptom scores, olfactory function, endoscopic findings, and type 2 inflammatory mediators (IL-4, IL-5, IL-13, IL-33, eotaxin-3, periostin) expression. Results: Postoperative olfactory Visual Analogue Scale (VAS) scores, T&T olfactometer scores, SNOT-22 scores, and Lund-Kennedy (LK) scores were reduced in patients with CRSwNP ( P < .01). Postoperative olfactory VAS scores, T&T olfactometer scores, SNOT-22 scores, and LK scores, IL-5, IL-13, and periostin were significantly lower in the stent group than in the control group ( P < .05). Correlation analysis was performed and found that the postoperative olfactory VAS scores were strongly correlated with IL-5 and IL-13 ( r = .496, P < .001 and r = .289, P = .026), and the postoperative T&T olfactometer scores were strongly correlated with IL-5 and IL-13 ( r = .553, P < .001 and r = .398, P = .002). Conclusions: Steroid-eluting stent implantation after ESS is an effective treatment for olfactory deficits in patients with CRSwNP and may be related to the stent’s more effective reduction of local type 2 inflammatory mediators in the nasal cavity.
Correlation between common iliac vein geometry and the risk of deep vein thrombosis in patients with May-Thurner syndrome
Authors: Ngo Dac Hong An , Nguyen Quoc Bao , Vo Quoc Huy , Le Minh Tuan , Huyen Ton Nu Hong Hanh , Nguyen Thanh Thao , Le Trong Binh 
Published: November 2024

Background May-Thurner syndrome (MTS) is a continuous pathological change of the left common iliac vein intraluminal wall due to compression between the right common iliac artery and a lumbar vertebra, with clinical signs of compromised venous drainage of the left leg, which eventually leads to development of left-sided deep vein thrombosis (DVT). Purpose To analyze the correlation between iliac vessel geometry and probability of DVT in patients with MTS. Material and Methods This study consists of two age-matched female groups: DVT (n = 21) and control (n = 28). Iliac vein geometry, including left common iliac vein (LCIV) diameter, percentage of stenosis, angle between LCIV and right common iliac vein (RCIV), tilt angle of each CIV with horizontal line, and crossing angle between right common iliac artery (RCIA) and LCIV, were measured on computed tomography venography (CTV) images. The probability of DVT development was assessed using logistic regression. Results Comparing the DVT and control groups, the mean LCIV diameter was 2.4 mm and 3.7 mm ( P = 0.001), and mean LCIV stenosis was 77.7% and 68.3% ( P = 0.001), respectively. After age-adjustment, the odds of left DVT in patients with MTS correlated with LCIV diameter (odds ratio [OR]=0.25, P < 0.001, 95% confidence interval [CI]=0.11–0.54), LCIV stenosis (%) (OR=1.12, P = 0.003, 95% CI=1.04–1.21), LCIV tilt angle (OR=0.95, P < 0.038, 95% CI=0.91–0.99), and angle between two CIVs (OR=1.04, P < 0.039, 95% CI=1.00–1.09). Conclusion LCIV diameter and percentage of stenosis, LCIV tilt angle, and CIV angle were independent risk factors for the development of DVT in patients with MTS.
Nomograms combining clinical factors and apparent diffusion coefficient to predict downstaging and progression-free survival after concurrent chemoradiotherapy in patients with cervical cancer
Authors: Fan Jiawei , Li Wenfei , Cheng Mengyu , Wang Zhehan , Wang Zhanqiu , Chen Tao , Gu Tao 
Published: November 2024

Background Concurrent chemoradiotherapy (CCRT) is used as the primary treatment modality for currently limited cervical cancer and lacks non-invasive quantitative parameters to assess clinical outcomes of treatment for cervical cancer treatment. Purpose To develop nomograms based on clinical prognostic factors and apparent diffusion coefficient (ADC) in predicting downstaging and progression-free survival (PFS) after CCRT for cervical cancer. Material and Methods X-tile was used to calculate the optimal threshold for ΔADCmean(%) for prognostic stratification. Kaplan–Meier curves were used to calculate the difference in PFS between high- and low-risk groups. Univariate and multivariate Cox proportional risk regression models were used to identify clinical and radiological risk factors for prognosis and construct a prognostic nomogram model. Results ΔADCmean(%) was significantly correlated with tumor downstaging; the area under the receiver operating characteristic curve (AUC) was 0.868. X-tile showed that the optimal threshold for ΔADCmean(%) to diagnose prognosis was 40.8. Kaplan–Meier curves showed that the low-risk population in the training group had significantly longer PFS within 3 years ( P < 0.001). Multivariate Cox regression showed that ΔADC (%) is independent risk factor for PFS. The C-index of ΔADC(%) predicting 3-year PFS in the training set is 0.761 and the C-index of the nomogram model is 0.862. Conclusion ΔADCmean(%) is a non-invasive biomarker for predicting tumor downstaging in cervical cancer after CCRT. The nomograms based on ΔADCmean(%) predict PFS of patients with cervical cancer with moderate accuracy.
Antiproliferative and Apoptotic Potential of Chicoric Acid, a Major Phytoconstituent of Cichorium intybus, against Colon Cancer Cells: A Possible Inhibition of CDC25 Phosphatases
Authors: Alotaibi Modhi O. , Verma Mahima , Fatima Shireen , Alotaibi Nahaa M. , Alshammari Nawaf , Saeed Mohd , Alharbi F. K. , Ansari Irfan Ahmad 
Published: November 2024

Background: Over the years, plants have been utilized worldwide for the treatment of cancer in the traditional system of medicine, notably in the majority of developing nations. The use of chemotherapeutic drugs is frequently associated with lethal side effects when treating cancer. Therefore, the panacea to the vicious side effects linked to synthetic pharmaceuticals is the alternative usage of widely accessible and affordable therapeutic approaches. Chicoric acid, a major constituent of Cichorium intybus, has recently been shown to exhibit antioxidant, anti-inflammatory, antidiabetic, antiviral, neuroprotective, hepatoprotective, and anticancer properties. Purpose: Except for a few preliminary studies, no detailed study on the chemotherapeutic efficacy of chicoric acid against cancer cells has been done till now. Therefore, the aim of this study is to assess the potential of chicoric acid against colon cancer cells. Methods: Different in vitro assays like MTT, DAPI staining, rhodamine staining, H2DCFDA staining, caspase activity, and cell analysis were performed on colon cancer HCT116 cells to assess their growth inhibitory properties. Results: According to the results, chicoric acid dose-dependently suppressed the growth of colon cancer HCT116 cells by inducing cell cycle arrest at G0/G1 phase and apoptosis via both intrinsic and extrinsic pathways. In silico findings unveiled the cell cycle regulatory capacity of chicoric acid through binding CDC25 phosphatases, implying its potential as an antiproliferative agent capable of suppressing cell growth. Conclusion: Collectively, the results suggested strong chemopreventive potential of chicoric acid against colon cancer cells. Thus, chicoric acid may turn out to be an excellent anticancer agent, which may be explored in the future for the therapeutic drug development against cancer.