bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Pimecrolimus on apoptotic pathways in H2O2-treated neuron like differentiated-SH-SY5Y cells: a molecular docking and mechanistic study
Authors: Kocanci Fatma Gonca 
Published: February 2025

Abstract
Neurodegenerative diseases (NDs), including Alzheimer’s and Parkinson’s, are marked by progressive neuronal loss, driven largely by oxidative stress and apoptosis. Developing neuroprotective strategies to counteract these processes is critical for managing such disorders. This study explores the neuroprotective effects of pimecrolimus, a calcineurin inhibitor, in mitigating hydrogen peroxide (H₂O₂)-induced cytotoxicity in neuron-like differentiated SH-SY5Y (d-SH-SY5Y) cells. The investigation focuses on apoptosis modulation, cell viability, and molecular docking interactions with apoptotic proteins.
SH-SY5Y cells were differentiated with retinoic acid and treated with H₂O₂ (250 μM) alone or in combination with pimecrolimus (0.01, 0.1, and 1 μM) for 24 h. Cell viability was assessed using lactate dehydrogenase (LDH) assays. Additionally, malondialdehyde (MDA) levels were measured to assess oxidative stress in SH-SY5Y cells following the treatment conditions. Molecular docking analyses evaluated pimecrolimus’ interactions with bax, bcl-2, caspase-3 and caspase-8 proteins, using Venetoclax as a positive control. Apoptosis-related protein levels were analyzed via ELISA, qRT-PCR, and immunofluorescence staining (cleaved caspase-3 and DAPI).
Molecular docking showed strong binding of pimecrolimus to bax, bcl-2, caspase-3 and caspase-8, with comparable binding energies to Venetoclax. LDH and MDA assays demonstrated significant reductions in H₂O₂-induced cytotoxicity with pimecrolimus. ELISA and qRT-PCR revealed that H₂O₂ increased pro-apoptotic bax, caspase-3 and caspase-8 levels while decreasing anti-apoptotic bcl-2 levels. Pimecrolimus co-treatment reversed these effects in a dose-dependent manner. Immunofluorescence confirmed reduced apoptosis and cell death with pimecrolimus.
Pimecrolimus effectively mitigates oxidative stress and apoptosis in H₂O₂-treated d-SH-SY5Y cells. These findings suggest its potential as a neuroprotective agent for managing (NDs).
Distribution of perfluorooctanoic acid in exposed female postpubertal pigs in thermal neutral or heat-stressed conditions
Authors: Good Samantha L , Antwi-Boasiako Collins , González-Alvarez M Estefanía , Buol Bridget M , Baumgard Lance H , Keating Aileen F , Charbonnet Joseph A 
Published: February 2025

Abstract
Perfluorooctanoic acid (PFOA), a legacy perfluoroalkyl substance with immuno- and repro-toxicant effects, has poorly characterized bioaccumulation and distribution patterns in postpubertal female pigs. The potential for heat stress (HS) to influence PFOA partitioning, potentially through intestinal hyperpermeability and alterations in systemic blood flow, also warrants investigation. This study investigated PFOA uptake, accumulation, and distribution in thermal neutral (TN) and heat-stressed gilts. Pigs (n = 48) were estrus synchronized and experienced TN (20 °C) or HS (26.6 to 32.2 °C) conditions during which they consumed 70 ng/kg bodyweight PFOA via cookie dough as vehicle control daily. Plasma was collected on d 1, 15, and 20. Liver, ovary, and follicular fluid were collected at euthanasia (d 20). Post-exposure, PFOA was detected in serum, liver, ovary, and follicular fluid. HS increased (P &lt; 0.05) plasma PFOA compared with TN pigs on d 15, but on d 20, plasma PFOA levels in TN and HS pigs were similar. Liver PFOA concentrations were similar between TN and HS pigs. Ovarian PFOA levels tended (P = 0.06) to be higher in TN relative to HS pigs, with an opposing pattern in follicular fluid, in which PFOA concentrations were greater (P &lt; 0.05) in HS pigs. These findings suggest that PFOA apportions to plasma, liver, ovary, and follicular fluid of exposed pigs and that HS alters PFOA distribution, which could negatively impact reproductive health. This study underscores the need to consider the interaction of HS and toxicant exposure in environmental health risk assessments.
Physiological adjustments of temperate tree species and herbs in response to low root temperatures
Authors: Li Yating , Hoch Guenter 
Published: February 2025

Abstract
Hydraulic constraints induced by low root temperature might be a major cause for the low temperature limit of plants. However, up to date most of our knowledge on the physiological effects of low root temperatures derived from short-term lab experiments, with very limited information on potential adjustments to continuous low temperature stress.
In this study, we quantified the cold sensitivity of root water uptake and transport to leaves in seedlings of different functional plant types (conifers, broadleaved trees and annual herbs) by 2H-H2O labelling after exposure to three constant root temperatures (15°C, 7°C and 2°C) but the same higher aboveground temperatures (between 20-25 °C). We investigated changes in the cold sensitivity of roots after 0, 10 and 20-days prolonged exposure to the respective root temperatures.
Plant water uptake and transport was decreased by lowered root temperature in all species, with a stronger effect at 2°C compared to 7°C. The water uptake and transport capacity of tree species gradually declined over the 20-day treatment, while the two investigated herbs exhibited immediately strong decreases that were kept at the same low level throughout the entire experiment time. The speed of the water uptake reduction across the 20 days observation period differed among the tree species and was faster in species that reach their natural upper distribution limits at lower elevations compared to species that occur at subalpine regions. The restricted root water uptake and transport was accompanied by reductions in leaf water potential, stomatal conductance and growth.
Overall, our study showed increasingly reduced capacity for water uptake and transport across functional plant groups at continuous cold root conditions. This result might indicate accumulative negative effects on cell membrane permeability for water in roots, or a controlled reduction of root water conductivity of temperate trees in preparation for winter dormancy.
OsHARBI1‐1 enhances cadmium tolerance in yeast through YAP1 mediated modulation of cell wall integrity genes and catalase genes
Authors: Shi Yang , Jiang Nan , Jiang Wenjun , Chen Ji , Wu Lijuan , Jiao Yuan , Zhou Yingxu , Wu Longying , Huang Yanyan , Li Deqiang , Kumar Vinod , Hu Binhua , Huang Jin 
Published: February 2025

AbstractHarbinger transposase‐derived 1 proteins (HARBI1s) play important roles in plant growth, development, and response to abiotic stress. OsHARBI1‐1 has been identified as a gene encoding HARBI1‐1 protein in rice and has been shown to be responsive to Cadmium (Cd) stress. However, the function of OsHARBI1‐1 protein under heavy metal stress remains unclear. In this study, the function of a novel rice Cd‐responsive gene, OsHARBI1‐1, under Cd stress was characterized by heterologous expression in yeast. The heterologous expression OsHARBI1‐1 conferred yeast with increased tolerance to Cd. In addition, the yeast cells expressing OsHARBI1‐1 exhibited enhanced tolerance to Congo red and exhibited an increase in cell wall thickness under Cd stress, suggesting a potential correlation between increased Cd tolerance and cell wall thickness in the transgenic yeast. When OsHARBI1‐1 was expressed in ∆yap1 or ∆yap1∆ycf1 yeast mutants, there was no significant difference in the tolerance of transgenic yeast to Cd and Congo red, as well as in cell wall thickness compared to the control. Meanwhile, the expression of cell wall integrity (CWI) genes and catalase genes in transgenic yeast was up‐regulated in a YAP1‐dependent manner under Cd or Congo red stress. The above facts supported the inference that OsHARBI1‐1 may counteract Cd toxicity by enhancing the expression of YAP1, thereby increasing the thickness of the cell wall and activating the expression of catalase genes.
Multi-institutional Analysis of Immune-Oncology Combination Therapy for Metastatic MiT Family Translocation Renal Cell Carcinoma
Authors: Ged Yasser , Touma Amina , Meza Contreras Luis , Elias Roy , Van Galen Joseph , Cupo Olivia , Baraban Ezra , Singla Nirmish , Lee Chung-Han , Pal Sumanta , Zibelman Matthew , Kotecha Ritesh R. 
Published: February 2025

Summary:
Metastatic translocation renal cell carcinomas (mtRCCs) are rare and aggressive tumors with limited treatment options. Recent studies demonstrated promising activity of immune-oncology (IO) combinations in mtRCC. However, the effectiveness of dual IO combinations versus IO plus VEGF-TKI combinations remains unclear. We conducted a retrospective analysis of IO combinations in mtRCC patients at 4 institutions. Eligible patients had confirmed mtRCC by genitourinary pathologist and received IO combination therapy (IO+IO or IO+VEGF-TKI). Clinical data and treatment outcomes were recorded from the start of systemic therapy. Objective response rate (ORR) was retrospectively evaluated, and time to treatment failure (TTF), and overall survival (OS) were compared for IO+IO and IO+VEGF-TKI groups. We identified 22 mtRCC patients who received IO combinations, all confirmed to have TFE3 rearrangement by FISH. Most patients were female (68%) with a median age of 41 years (16–79). Treatment breakdown included: IO+IO (n=8, 36%) and IO+VEGF-TKI (n=14, 64%). In the evaluable patients for the efficacy analysis, ORR was 14% (1/7) for the IO+IO group and 54% (6/11) for the IO+VEGF-TKI group. With a median follow-up of 32.4 months, the median TTF was 1.2 months and 6.2 months in the IO+IO and IO+VEGF-TKI groups, respectively (P=0.12). There was no statistically significant difference in median OS between both groups, 36.7 months in the IO+IO group and 15.6 months in IO+VEGF-TKI (P=0.9). Our findings demonstrate that IO+VEGF-TKI resulted in higher ORR and TTF point estimates without statistically detectable differences, compared with IO+IO therapy. Larger studies are needed to validate these findings and optimize treatment selection.
Impact of Consensus Guidelines, Clinical Trials, and COVID-19 on Fractionation Practices for Node-negative Intact Breast Cancer
Authors: Cruttenden Jessica , Grant Jonathan , Evans Jaden , Cannon George , Gaffney David K. , Poppe Matthew , Burt Lindsay M. , Avizonis Vilija , Boothe Dustin 
Published: February 2025

Objective:
To evaluate whether hypofractionated radiotherapy (HF-RT) in node-negative intact breast cancer significantly increased after guideline updates, trial publications, and COVID-19.

Methods:
Patients with node-negative breast cancer undergoing lumpectomy and adjuvant RT were identified in the National Cancer Database. Receiving ≥25 and <50 Gy in 5-20 fractions defined HF-RT. Receiving 50 to 66 Gy in >20 fractions defined conventional RT (CF-RT). Patient characteristics were compared with X2 testing. Joinpoint analysis identified when fractionation significantly changed. Variables associated with HF-RT were identified by univariate and multivariate (MVA) logistic regression. Two-sided P-value <0.05 was significant.

Results:
Patients meeting criteria totaled 236,336; 54.8% received CF-RT and 45.2% HF-RT. HF-RT and 5-fraction RT significantly increased after 2015 and 2019, respectively (P<0.05). On MVA, HF-RT was positively associated with: age older than or equal to 65 years (OR 2.14, P<0.001); private insurance (OR 1.27, P=0.03); treatment in Midwest (OR 1.66, P<0.001) or Western United States (US) (OR 3.77, P<0.001); distance ≥50 miles (OR 1.16, P=0.001); later year of diagnosis (OR 1.44, P<0.001); and partial breast irradiation (OR 2.08, P<0.001). HF-RT was negatively associated with: community (OR 0.49, P<0.001) or integrated network (0.55, P<0.001) centers; grade 2 (OR 0.83, P<0.001) or 3 (OR 0.49, P<0.001), hormone receptor negative (OR 0.66, P<0.001), and HER2+ (OR 0.74, P<0.001) disease; positive surgical margins (OR 0.61, P<0.001); and presence of lympho-vascular invasion (OR 0.86, P<0.001).

Conclusions:
HF-RT in node-negative intact breast cancer increased after 2015, coinciding with US and European guideline updates. Five-fraction RT increased after 2019, coinciding with COVID-19 and FAST-Forward trial results.
Mucosal immunity in acute HIV: a review of recent work
Authors: Shacklett Barbara L. 
Published: February 2025

Purpose of review
This review summarizes recent research literature relevant to mucosal immunity and acute/early HIV infection.

Recent findings
Recent findings include new insights on the HIV transmission “bottleneck” at mucosal surfaces, the impact of acute HIV on germinal centers and mucosal B-cell function, the expression of cytotoxic effector molecules by mucosal CD8+ T-cells, and an enhanced understanding of the impact of acute HIV on innate cell-mediated defenses including mucosa-associated invariant T-cells invarant natural killer T-cells and natural killer cells.

Summary
Now more than 40 years since the beginning of the HIV/AIDS pandemic, extensive research has elucidated the dynamics of HIV replication and the corresponding host response. However, the vast majority of HIV-related immunopathogenesis studies have focused on innate and adaptive immune responses in peripheral blood. Mucosal tissues serve as the primary portals of entry for HIV and house the majority of the body's lymphocytes. Innate and adaptive immune responses in mucosal tissues are of particular relevance during the acute phase of HIV disease, as successful defenses can both limit viral dissemination within the host and prevent transmission to a new host, yet until recently these responses were poorly understood.
Population Pharmacokinetics of Perampanel in Chinese Pediatric and Adult Patients With Epilepsy
Authors: Yang Jiayu , Zhang Sitian , Zhao Zhigang , Mei Shenghui , Feng Weixing 
Published: February 2025

Background:
Perampanel is a promising epilepsy treatment with an innovative mechanism of action. This study was performed to investigate the factors affecting perampanel clearance in a population pharmacokinetic (PPK) model of Chinese pediatric and adult patients with epilepsy.

Methods:
A total of 135 perampanel plasma concentrations from 125 patients with epilepsy were analyzed using the PPK model with nonlinear mixed-effects modeling. One-compartment and proportional residual models best described the pharmacokinetics of perampanel. Covariate effects on the model parameters were assessed using forward and backward elimination. Goodness-of-fit, bootstrapping, visual predictive checks, and normalized prediction distribution errors were used to evaluate the model. Monte Carlo simulations were conducted to assess the impact of covariate combinations on perampanel plasma concentrations at different dosages.

Results:
In the final PPK model, body weight (BW), concomitant carbamazepine (CBZ), oxcarbazepine (OXC), and C-reactive protein (CRP) levels significantly influenced perampanel clearance. The interindividual clearance was calculated as follows: 0.84 × (BW/70)0.53 × eCBZ × eOXC × eCRP (CBZ = 0.98, when comedicated with carbamazepine; OXC = 0.43, when comedicated with oxcarbazepine; CRP = −0.69, when CRP >15 mg/L, otherwise = 0). The estimates (relative standard error) for clearance and apparent volume of distribution of the final model were 0.84 L/h (8.75%) and 64.35 L (19.78%), respectively. The model maintained its stability and effectiveness with moderate predictability.

Conclusions:
BW and CBZ, OXC, and CRP levels may influence perampanel clearance in both pediatric and adult patients with epilepsy according to a population pharmacokinetic model that included real-world data.
Management and Outcomes of Coronary Artery Aneurysms: A Patient-level Systematic Review
Authors: Rahimov Daler , Nasher Nayeem , Ahmad Danial , Morris Rohinton J. , Upadhyaya Anjali , Yost Colin , Wong Daniella , Patel Preeyal , Vishnevsky Alec , Ruggiero Nicholas J. , Entwistle John W. , Tchantchaleishvili Vakhtang 
Published: February 2025

Background:
Data are lacking to guide standardized management of coronary artery aneurysms (CAA). We sought to analyze the available evidence in a quantitative manner.

Methods:
Electronic search identified 431 case reports or case series on CAA, comprising 488 patients. Patient-level data were extracted. Subgroups with (CAAF) and without fistulous connections (CAAO) were analyzed separately.

Results:
Fistulous connection was present in 24.0% (117/488) of patients with CAA. Angina was a presenting symptom in 64.7% (301/465), with higher preponderance in the CAAO group [CAAO: 71.1 % (249/350) vs CAAF: 45.2% (52/115), p<0.01). Median largest aneurysm diameter was higher in the CAAF group [CAAO: 3.0 [1.5–5.0] cm vs CAAF: 5.0 [3.0–7.0], p<0.01], and rupture was more frequently observed in the CAAF group [CAAO: 3.1% (11/353) vs CAAF: 13.8% (16/116), p<0.01]. For any given diameter, CAAF had a higher risk of rupture compared to CAAO. Surgery was the most common management strategy, particularly in patients with CAAF [CAAO: 50.9% (189/371) vs CAAF: 75.2% (88/117), p<0.01]. Kaplan-Meier analysis showed a trend toward more favorable survival in CAAF. Hazard of mortality was associated with aneurysm diameter in both subsets but was higher in the CAAO group independent of surgical vs interventional management.

Conclusion:
CAAF appears to have a higher risk of rupture but may be associated with better survival than CAAO. Management for patients with CAA differs based on presence or absence of fistula, however, both surgical and interventional mode of management result in similar survival.
Optical coherence tomography features of atypical congenital hypertrophy of retinal pigment epithelium in a patient with familial adenomatous polyposis
Authors: Mennecozzi Stefano , Spada Elena , Sacconi Riccardo , Bandello Francesco , Querques Giuseppe 
Published: February 2025

Purpose:
To describe optical coherence tomography (OCT) features of atypical congenital hypertrophy of retinal pigment epithelium (CHRPE) associated with familial adenomatous polyposis (FAP).

Methods:
Case report.

Results:
A 34-year-old patient diagnosed with FAP was referred to our clinic for fundus examination. We characterized the lesions we found using multimodal imaging (infrared, autofluorescence, OCT and widefield and ultra-widefield fundus image). We described 3 possible stages of progression of the lesions in a single patient and we found a possible evolutionary stage with a “2 binary reflective sign”.

Conclusions:
CHRPE lesions can show a progression from only retinal pigment epithelium (RPE) hyperreflectivity to complete outer retinal atrophy and even intraretinal RPE migration. We hypothesize that the 2 binary reflective sign could represent an hemorrhage between RPE and outer retina which could lead, together with the reduced catabolic activity of pathological RPE, to overlying retinal atrophy.
Evaluation of the Long-Term Effects of Selective Laser Trabeculoplasty on Patients with Primary Open Angle Glaucoma
Authors: Lanza Michele , Serra Luigi , Boccia Rosa , Cangiano Teresa , Coniglio Maria , Fattore Italo , Simonelli Francesca 
Published: February 2025

Precis:
Data coming from this study suggest that selective laser trabeculoplasty could be a very important tool in the overall management of glaucoma patients at every stages, aiming to better control the visual field deterioration.

Purpose:
To evaluate selective laser trabeculoplasty (SLT) effectiveness in lowering intraocular pressure (IOP) and in visual field defect progression in eyes affected by primary open angle glaucoma (POAG) at long term follow up.

Methods:
A retrospective study were conducted with 67 eyes of 67 patients affected by POAG who underwent SLT between 2014 and 2021. Each patient was routinely observed in the Glaucoma Office of Università della Campania Luigi Vanvitelli and underwent a complete eye visit and visual field (VF) test with 30-2 SITA standard automated perimetry (SAP) every 6 months. When both eyes in same patient were treated, only the eye with lower mean deviation (MD) of SAP was included. Patients were observed at 6, 12, 18, 24, 30, 36, 42, 48, 54 months.

Results:
A mean significant (P<0.01) lower IOP was detected at 6 months (12.92±2.7 mm Hg) ad at 54 months (13.08±2.42 mm Hg) compared to baseline (17.91±4 mm Hg). Mean MD values showed significant (P<0.01) reduction both at 6 month follow up (−0.07±0.21 dB) and at 54 month follow up (−0.3±0.34 dB) demonstrating satisfactory clinical deceleration of the progression of the disease.
Mean IOP medical lowering therapy was 1.34±0.9 drugs, showing a significant (P<0.01) decrease 6 months after SLT (0.87±0.85), that remained stable (P= at 54 month follow up (0.9±0.76).

Conclusions:
The results observed confirm not only the high level of effectiveness of SLT in lowering IOP and reducing the need for topical medications, but also its role in decelerating visual field deterioration in eyes affected by POAG.
Walking More Than 10,000 Steps Per Day May be Associated with Increased Optic Disc Vessel Density in Patients With Primary Open Angle Glaucoma
Authors: Liang Yuanbo , Yu Yun , Wen Xin , Wang Mei , Lan Yuqing , Pan Xiafei 
Published: February 2025

Purpose:
The study aimed to investigate the relationship between average daily steps (ADS) and optic disc angioflow vessel density (VD) in patients with primary open angle glaucoma (POAG).

Materials and Methods:
This is a cross-sectional study. Forty-one POAG patients (74 eyes) were recruited from Wenzhou Glaucoma Progression Study (WGPS) who were divided into two groups based on international physical activity guidelines: 21 subjects (38 eyes) in the ADS>10,000 group and 20 patients (36 eyes) in the ADS≤10,000 group. ADS was monitored using a waist-worn accelerometer (ActiGraph wGT3x-BT) worn on the waist for seven consecutive days, while optic disc VD was assessed by the optical coherence tomography angiography.

Results:
Papillary VD was significantly denser in the ADS>10,000 group (ADS:12782±2925) compared to the ADS≤10,000 group (ADS:7418±1543) for both whole image-all VD (WIAVD) and whole image-capillary VD (WICVD) (P=0.026, 0.032, respectively). Univariate analysis indicates that WIAVD was more denser in ADS>10,000 vs ADS≤10,000 (P=0.013) and that WICVD was more denser in ADS>10,000 vs ADS≤10,000 (P=0.019). Furthermore, every 1 μm thicker in retinal nerve fiber layer (RNFL) thickness was associated with a 0.24 denser in WIAVD (P<0.0001) and a 0.23 denser in WICVD (P<0.0001). Each 1-dB improvement in mean deviation (MD) was linked to a 0.75 increase in WIAVD (P<0.0001) and a 0.83 increase in WICVD (P<0.0001). Additionally, a 1 mmHg increase in intraocular pressure was associated with a 0.5 decrease in WIAVD (P<0.009) in univariate analysis and a 0.31 decrease in multivariate analysis (P<0.012). Multivariate analysis revealed that patients with ADS>10,000 had 1.75 higher WIAVD and 1.64 higher WICVD compared to those with ADS≤10,000 after adjusting for other risk factors.

Conclusion:
POAG patients with ADS>10,000 exhibited higher papillary VD compared to those with ADS≤10,000, implying that increasing daily steps, particularly exceeding 10,000 steps, may potentially enhance ocular blood flow.