bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell type-specific DNA replication initiation and termination in human primary cancer whole genomes
Authors: Peifer Martin , Yang Tsun-Po , Etich Julia , Acht Torsten , Cartolano Maria , George Julie , Thomas Roman , Fischer Matthias 
Published: September 2023

Abstract
The understanding of where exactly, and how differently, DNA replication starts and ends in the cancer genomes remain limited. Although DNA sequences that underwent somatic alterations across human primary cancers have been comprehensively studied, the entire accurately replicated sequences of the same primary cancer genomes have not been widely explored. Here, we present a novel in silico framework to assess the tumour replication timing (RT) programme directly using 256 primary cancer whole genomes across three tumour types. We introduce a novel bootstrap-based replication fork directionality (RFD) method to model the bi-directional replication, and simultaneously map the replication origin and terminus domains at 1 kb resolution. ﻿Unexpectedly, our high-resolution results suggest that the genome-wide distribution of termination zones (TZs) is tightly coordinated with the initiation zones (IZs) in both normal and cancer genomes, which has not been previously reported using in vitro directional sequencing of Okazaki fragments (OK-seq) method. Overall, our data demonstrate that the cell type specificity of the tumour replication timing domains is preserved in closely related normal tissues and in lineage-specific cancer cell lines. Finally, comparing altered replication initiations between normal and cancer genomes, our data identifies delocalisation of replication initiations near highly expressed proliferation-associated PIF1 gene in small cell lung cancer (SCLC) genome, suggesting a potential cancer-specific target.
Repurposing dimethyl fumarate as an antiepileptogenic and disease-modifying treatment for drug-resistant epilepsy
Authors: Sandouka Sereen , Singh Prince Kumar , Saadi Aseel , Taiwo Rhoda Olowe , Sheeni Yara , Zhang Taige , Deeb Larin , Guignet Michelle , White Steve H. , Shekh-Ahmad Tawfeeq 
Published: September 2023

Abstract
Background
Epilepsy affects over 65 million people worldwide and significantly burdens patients, caregivers, and society. Drug-resistant epilepsy occurs in approximately 30% of patients and growing evidence indicates that oxidative stress contributes to the development of such epilepsies. Activation of the Nrf2 pathway, which is involved in cellular defense, offers a potential strategy for reducing oxidative stress and epilepsy treatment. Dimethyl fumarate (DMF), an Nrf2 activator, exhibits antioxidant and anti-inflammatory effects and is used to treat multiple sclerosis.
Methods
The expression of Nrf2 and its related genes in vehicle or DMF treated rats were determined via RT-PCR and Western blot analysis. Neuronal cell death was evaluated by immunohistochemical staining. The effects of DMF in preventing the onset of epilepsy and modifying the disease were investigated in the kainic acid-induced status epilepticus model of temporal lobe epilepsy in rats.
The open field, elevated plus maze and T-Maze spontaneous alterations tests were used for behavioral assessments.
Results
We demonstrate that administration of DMF following status epilepticus increased Nrf2 activity, attenuated status epilepticus-induced neuronal cell death, and decreased seizure frequency and the total number of seizures compared to vehicle-treated animals. Moreover, DMF treatment reversed epilepsy-induced behavioral deficits in the treated rats.
Moreover, DMF treatment even when initiated well after the diagnosis of epilepsy, reduced symptomatic seizures long after the drug was eliminated from the body.
Conclusions
Taken together, these findings suggest that DMF, through the activation of Nrf2, has the potential to serve as a therapeutic target for preventing epileptogenesis and modifying epilepsy.
Evaluation of large language models for discovery of gene set function
Authors: Pratt Dexter , Hu Mengzhou , Alkhairy Sahar , Lee Ingoo , Pillich Rudolf , Bachelder Robin , Ideker Trey 
Published: September 2023

Abstract

Gene set analysis is a mainstay of functional genomics, but it relies on manually curated databases of gene functions that are incomplete and unaware of biological context. Here we evaluate the ability of OpenAI’s GPT-4, a Large Language Model (LLM), to develop hypotheses about common gene functions from its embedded biomedical knowledge. We created a GPT-4 pipeline to label gene sets with names that summarize their consensus functions, substantiated by analysis text and citations. Benchmarking against named gene sets in the Gene Ontology, GPT-4 generated very similar names in 50% of cases, while in most remaining cases it recovered the name of a more general concept. In gene sets discovered in ‘omics data, GPT-4 names were more informative than gene set enrichment, with supporting statements and citations that largely verified in human review. The ability to rapidly synthesize common gene functions positions LLMs as valuable functional genomics assistants.
Unexpected long-term variations of Saturn’s ring current revealed by energetic neutral atom imaging
Authors: Yue C. 
Published: September 2023

Abstract

In a magnetosphere, the inhomogeneity of the magnetic field leads to gradient and curvature drifts of charged particles. Ions and electrons drift in opposite directions, leading to a transverse current known as the “ring current”, whose radial profile, intensity and thickness depend on the properties of the plasma ions and electrons. Ring current is an essential part of Saturn’s magnetospheric current system. Previous studies have used in-situ magnetic field or charged particle measurements to analyze its characteristics, and constructed corresponding distribution models. However, those models can only present a long-term average of the ring current distribution due to the limited spatial coverage from individual spacecraft orbits. In contrast, energetic neutral atom (ENA) imaging provides us with a complementary and effective method to observe the global distribution of energetic particles, which enables statistics over a shorter interval. In this study, we make use of ENA imaging observations from Cassini to statistically analyze the ring current, which reveals previously unexpected long-term variations. We suggest these variations are driven by both solar cycle and seasonal variations, which may influence the energetic particle acceleration process, primarily magnetic reconnection.
Statin Improves Early-Phase Obesity-Induced Renal Injury via Restoring Autophagy Failure Through Rho/Rho Kinase/mTOR Pathway Inhibition
Authors: Yasuda Marie , Tokuyama Hirobumi , Kanda Takeshi , Hasegawa Kazuhiro , Wakino Shu , Itoh Hiroshi , Hayashi Kaori , Adachi Keika , Yasuda Itaru 
Published: September 2023

Abstract
Obesity-induced renal injury serves as a preceding phase to the majority of diabetic nephropathy. We investigated the cascading pathophysiology of renal dysfunction induced by obesity and, as a result, identified the significant role of disrupted autophagy within the proximal tubular cells. In mice subjected to obesity induction through a high-fat diet, we observed weight gain, increased adipose tissue mass, decreased glucose tolerance, and insulin resistance, accompanied by the expression of albuminuria. This was further associated with glomerular hypertrophy and tubular epithelial cell enlargement. Among the histological changes, the most prominent was the enlargement of tubular epithelial cells, within which we witnessed substantial lipid accumulation in lysosomes. This observation indicated signs of autophagy dysfunction, raising the possibility that mTOR-mediated autophagy impairment in obesity could be a significant factor in renal function deterioration. Therapeutic intervention with statins, inhibiting the Rho/Rho kinase, simultaneously suppressed the Rho and mTOR cascades, ameliorating autophagy dysfunction. This intervention led to histological improvements and a reduction in albuminuria. The potential of statins to ameliorate changes in tubular and glomerular structures induced by obesity became evident, suggesting their viability as an effective therapeutic strategy for obesity- induced renal injury.
Systemic inflammation plays a central role in sarcopenia and prognosis of patients with metastatic colorectal cancer: A retrospective study
Authors: Yang Ran , Tang Hui-juan , Qiu Wen-li , Ma Yu-yang , Shu Peng 
Published: September 2023

Abstract
Background
Systemic inflammatory response (SIR) affects the prognosis of metastatic colorectal cancer (mCRC) and is reportedly a crucial triggering factor for sarcopenia. Furthermore, sarcopenia has recently been reported to be associated with shorter overall survival in patients with mCRC; however, the existing evidence is insufficient and inconsistent. Therefore, we aimed to investigate the impact of the body composition of patients on the prognosis of mCRC in relation to the SIR.
Methods
This retrospective study collected data from 317 patients with mCRC in China between January 2015 and 2020. The data of patients at baseline and after three cycles of first-line treatment were evaluated, primarily including modified Glasgow Prognostic Score (mGPS) [inflammation level calculated using C-reactive protein (CRP) and albumin], body composition parameters [total adipose tissue index, total adipose tissue density, skeletal muscle index (SMI), and skeletal muscle density (SMD)], and overall survival. The Kaplan–Meier survival curve was drawn to verify the predictive effect of mGPS on overall survival. Furthermore, non-parametric tests and the empirical cumulative distribution function were used to evaluate the relationship between mGPS and body composition and univariate and multivariate Cox regression analysis was used to determine the factors related to the prognosis of mCRC.
Results
In our cohort, the survival curve showed that the baseline mGPS had a strong predictive effect on overall survival. The empirical cumulative distribution function showed that a high mGPS level was associated with a low baseline SMD and SMI and a low SMI after treatment, indicating a significant correlation between sarcopenia and mGPS. Univariate analysis showed that factors affecting prognosis included CRP, albumin, mGPS, and specific body compositions. In multivariate analysis, only mGPS retained independent prognostic value, and a high baseline mGPS level indicated poor prognosis.
Conclusions
Regarding SIR, we found that body composition and overall survival were affected in patients with mCRC, and sarcopenia and poor prognosis had no direct causal relationship. Furthermore, mGPS was found to be a simple and effective prognostic factor; therefore, it should be monitored during treatment. These findings could help clinicians formulate effective individualised anti-inflammatory strategies and improve the prognosis of mCRC.
Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-GFP mice
Authors: Gerber Susanne , Butto Tamer , Winter Jennifer , Chongtham Monika , Hartwich Dewi , Linke Matthias , Ruffini Nicolas , Radyushkin Konstantin , Schweiger Susann , Mungikar Kanak 
Published: September 2023

Abstract
Chronic stress has become a predominant factor associated with a variety of psychiatric disorders, such as depression and anxiety, in both humans and animal models. Although multiple studies have looked at transcriptional changes after social defeat stress, these studies mostly focus on bulk tissues, which might dilute important molecular signatures of social interaction in activated cells. In this study, we employed the Arc-GFP mouse model in conjunction with chronic social defeat (CSD) to selectively isolate activated nuclei (AN) populations in the ventral hippocampus (vHIP) and prefrontal cortex (PFC) of resilient and susceptible animals. Nuclear RNA-seq of susceptible vs. resilient populations revealed distinct transcriptional profiles linked predominantly with neuronal and synaptic regulation mechanisms. In the vHIP, susceptible AN exhibited increased expression of genes related to cytoskeleton and synaptic organization while resilient AN showed upregulation of cell adhesion genes and differential expression of major glutamatergic subunits. In the PFC, susceptible mice exhibited upregulation of synaptotagmins, and immediate early genes (IEGs), suggesting a potentially over-amplified neuronal activity state. Our findings provide a novel view of stress-exposed neuronal activation and the molecular response mechanisms in stress-susceptible versus resilient animals, which may have important implications for understanding mental resilience.
Midwives’ lived experiences of caring for women with mobility disabilities during pregnancy, labour and puerperium in Eswatini: A qualitative study
Authors: Magagula Fortunate , Temane Annie , Nolte Anna 
Published: September 2023

Abstract
Background
Midwives encounter various difficulties while aiming to achieve excellence in providing maternity care to women with mobility disabilities. The study aimed to explore and describe midwives’ experiences caring for women with mobility disabilities during pregnancy, labour and puerperium in Eswatini and formulate guidelines to facilitate support and holistic maternity care for these women.
Methods
A qualitative, exploratory, descriptive, contextual research design with a phenomenological approach was followed. Twelve midwives working in maternal health facilities in the Hhohho and Manzini regions in Eswatini were interviewed. Purposive sampling was used to select midwives to participate in the research. In-depth phenomenological interviews were conducted, and Giorgi’s descriptive phenomenological method was used for data analysis.
Results
Three themes emerged from the data analysis: midwives experienced physical and emotional strain in providing maternity care to women with mobility disabilities, they experienced frustration due to the lack of equipment to meet the needs of women with mobility disabilities, and they faced challenges in providing support and holistic care to women with mobility disabilities during pregnancy, labour and puerperium.
Conclusions
Midwives experienced challenges caring for women with mobility disabilities during pregnancy, labour and the puerperium in Eswatini. There is a need to develop and empower midwives with the knowledge and skill to implement guidelines and enact protocols. Moreover, equipment and infrastructure are required to facilitate support and holistic maternity care for women with mobility disabilities.
Sustainable Astronomy: A comparative Life Cycle Assessment of Off-grid Hybrid Energy Systems to supply large Telescopes
Authors: Viole Isabelle , Shen Li , Camargo Luis Ramirez , Zeyringer Marianne , Sartori Sabrina 
Published: September 2023

Abstract

Purpose
Supplying off-grid facilities such as astronomical observatories with renewable energy-based systems (RES) instead of diesel generators can considerably reduce their environmental impact. However, RES require oversized capacities to counter intermittency and comply with reliability requirements, hence shifting the environmental impact from operation to construction phase. We assess whether 100% RES scenarios are favorable from an environmental point of view, and discuss the trade-offs in systems with backup fossil generators versus 100% renewable ones.
Methods
In this comparative life cycle assessment (LCA), we study various RES supply systems to power a new telescope in the Atacama desert, Chile. We compare six setups, including 100% RES scenarios, namely photovoltaics (PV) with batteries and hydrogen energy storage; high-renewable scenarios, with fossil fuel power generation next to RES and storage; and a system combining PV with diesel generation. We base system sizing on a techno-economical optimization for the start of operation in 2030. Foreground data stem from recent life cycle inventories of RES components and 2030 electricity mix assumptions of production places. We assess environmental impact in the categories climate change, mineral resource depletion and water use.
Results and discussion
We find that 100% RES and high-renewable scenarios result in emissions of 0.077-0.115kg CO2e/kWh supplied, compared to 0.917kg CO2e/kWh in the reference case with solely diesel generation. 100% RES scenarios have a lower CO2e impact than high-renewable scenarios. However, the latter lower the mineral resource depletion and water use by about 27% compared to 100% RES scenarios. Applying hybrid energy storage systems increases the water use impact, while reducing the mineral resource depletion.
Conclusions
None of the six energy systems we compared was clearly the best in all environmental impacts considered. Trade-offs must be taken when choosing an energy system to supply the prospective off-grid telescope in Chile. We find high-renewable systems with some fossil generation as the better option regarding power reliability, mineral resource depletion and water use, while inducing slightly higher greenhouse gas emissions than the 100% RES scenarios.
As remote research facilities and off-grid settlements today are mainly supplied by fossil fuels, we expect to motivate more multifaceted decisions for implementing larger shares of RES for these areas. To advance the LCA community in the field of energy systems, we should strive to incorporate temporal and regional realities into our life cycle inventories. To ease the path for upcoming studies, we publish this work’s inventories as detailed activity level datasets.
Assessment of the seasonal and altitudinal gradients in fish diversity of a tropical river of western ghats biosphere using multivariate analysis
Authors: PAUL THANKAM Theresa , Sudheesan Deepa , Saha Ajoy , Madayil Roshith Chakkiyath , Suresh Vettath Raghavan , Sharma Sravan , Manoharan Shanmugham , Ratheesan Athira Nambrattil , Ramachandran Srinath , Srika Samantha 
Published: September 2023

Abstract
The study attempted to investigate the seasonal and spatial (altitudinal) gradients in fish diversity with respect to hydrobiological variables of Chaliyar river (encompassed in western Ghats biosphere). Fish and water quality samples were collected seasonally and analysed inorder to identify the drivers determining fish diversity of the river. 66 fish sp. belonging to 57 families and 12 orders were recorded during the study period (2017–2020). The year-wise diversity analysis revealed that higher diversity was recorded in 2019(1.43) compared to 2018. Seasonal and altitudinal (stretch wise) diversity analysis showed that the pre-monsoon season of 2017 (3.19) and lower stretch (2.18) of the river recorded the highest diversity. Phosphate (0.036ppm ± 0.039), calcium hardness (35.18 ± 101.61ppm), transparency (1.04 ± 0.6m), total hardness (330.21 ± 795.66ppm), and magnesium hardness (60.57ppm ± 142.42) were positive drivers influencing the diversity of Chaliyar as assessed using step-wise regression. Majority of fishes belong to least concern category except Horabagrus brachysoma (yellow spotted catfish) and Bhavania australis (westernghat loach). Community mobilisation, enhanced scientific interpretation and identification of appropriate habitat indices would be considered the next step in devising management measures in Chaliyar river.
Geomorphological and Geotechnical Investigations of Shallow-rainfall Induced Landslides Along Murree Expressway, a Case Study of Khajut Landslide, District Rawalpindi, Pakistan
Authors: Ahmed Shahid , Hussain Khadim , Lu Baoliang , Ishtiaq Muhammad 
Published: September 2023

Abstract
Landslide is a recurrent environmental hazard in the hilly regions and effects the socioeconomic development in Pakistan. The study area lies in the Tehsil Murree, Western Himalayas, Pakistan. The present study deals with detailed geomorphological mapping and geotechnical investigations of shallow rainfall-induced landslide i.e., Khajut Landslide, the Murree Expressway. The extensive field survey and detailed geomorphological, geological mapping and laboratory testing was carried out. Based on field observations, geotechnical investigations and longitudinal profiling, the Khajut landslide is classified as a rotational slide. The slope angle of the Khajut landslide is > 42º. The particle size distribution analysis of soil samples of Khajut landslide indicate that the landslide body consists of coarser particles i.e., sand and gravels. The average specific gravity of the soil sample collected from the Khajut landslide range from 2.89 kg/m3. The liquid limit of Khajut landslide soil samples ranges from 14%- 19%. The plasticity chart shows that soil is inorganic silt and inorganic clays of low to medium plasticity. The plastic limit of Khajut landslide ranges from 5%- 16%. Based on these results, it is concluded that frequent, cyclic wetting & drying during heavy rainfall strongly influence the shrink & swell behavior of the soil on the studied landslide which as a result can deform soils & damage Murree Expressway and other man-made structures.
An update of Clinical value of circulating tumor DNA in esophageal cancer： a systematic review and meta- analysis
Authors: Zhang Yaozhong , Du Huazhen , Wang Na , Wang Lei , Hang Yajie 
Published: September 2023

Abstract
Background
Esophageal cancer is a deadly disease with limited therapeutic options. Circulating tumor DNA (ctDNA) could be a promising tool in this regard, although the data is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and list its current challenges.
Methods
We systematically searched MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library from January, 2000 to April, 2023. Progression-free survival (PFS) and overall survival (OS) were set as primary outcome endpoints. Pathologic response was evaluated by tumor regression grade (TRG), accord to the eighth edition of the American Joint Committee on Cancer (AJCC). Major pathologic regression (MPR) was defined as TRG 1 and 2. The MPR was set as secondary endpoint. Hazard rate (HR) and associated 95% CI were used as the effect indicators the association between ctDNA and prognosis of EC. MPR rates were also calculated. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity.
Results
Twenty-two studies, containing 1144 patients with EC, were included in this meta-analysis. The results showed that OS (HR = 3.87; 95% CI, 2.86–5.23) and PFS (HR = 4.28; 95% CI, 3.34–5.48) were worse in ctDNA-positive patients. In the neoadjuvant therapy, the sensitivity analysis showed the clarified HR of ctDNA-positive was 1.13(95% CI, 1.01–1.28). In addition, the estimated MPR rate was 50% (95%CI:14%-86%) of patients changed positive to negative; and 51% (95%CI:33%-69%) for patients kept negative from beginning to end. We also found that TP53, NOTCH1, CCND1 and CNKN2A are most frequent mutation genes.
Conclusions
Detection of ctDNA had prognostic value for EC patients. Positive ctDNA is associated with poor prognosis. A standardized technique needs to be established in order to introduce ctDNA analysis into routine clinical practice. Longitudinal ctDNA monitoring might be a better strategy in the neoadjuvant therapy. In an era of personalized medicine, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in esophageal cancer.