bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinations, chains and caps: resolving problems with the DCJ-indel model
Authors: Bohnenkämper Leonard 
Published: February 2024

AbstractOne of the most fundamental problems in genome rearrangement studies is the (genomic) distance problem. It is typically formulated as finding the minimum number of rearrangements under a model that are needed to transform one genome into the other. A powerful multi-chromosomal model is the Double Cut and Join (DCJ) model.While the DCJ model is not able to deal with some situations that occur in practice, like duplicated or lost regions, it was extended over time to handle these cases. First, it was extended to the DCJ-indel model, solving the issue of lost markers. Later ILP-solutions for so called natural genomes, in which each genomic region may occur an arbitrary number of times, were developed, enabling in theory to solve the distance problem for any pair of genomes. However, some theoretical and practical issues remained unsolved. On the theoretical side of things, there exist two disparate views of the DCJ-indel model, motivated in the same way, but with different conceptualizations that could not be reconciled so far. On the practical side, while ILP solutions for natural genomes typically perform well on telomere to telomere resolved genomes, they have been shown in recent years to quickly loose performance on genomes with a large number of contigs or linear chromosomes. This has been linked to a particular technique, namely capping. Simply put, capping circularizes linear chromosomes by concatenating them during solving time, increasing the solution space of the ILP superexponentially. Recently, we introduced a new conceptualization of the DCJ-indel model within the context of another rearrangement problem. In this manuscript, we will apply this new conceptualization to the distance problem. In doing this, we uncover the relation between the disparate conceptualizations of the DCJ-indel model. We are also able to derive an ILP solution to the distance problem that does not rely on capping. This solution significantly improves upon the performance of previous solutions on genomes with high numbers of contigs while still solving the problem exactly and being competitive in performance otherwise. We demonstrate the performance advantage on simulated genomes as well as showing its practical usefulness in an analysis of 11 Drosophila genomes.
An innovative lab-scale production for a novel therapeutic DNA vaccine candidate against rheumatoid arthritis
Authors: Long Juan , Zhao Xiao , Liang Fei , Zeng Yang , Liu Nan , Sun Yuying , Xi Yongzhi 
Published: February 2024

Abstract
Background
Recent therapeutic-plasmid DNA vaccine strategies for rheumatoid arthritis (RA) have significantly improved. Our pcDNA-CCOL2A1 vaccine is the most prominent and the first antigen-specific tolerising DNA vaccine with potent therapeutic and prophylactic effects compared with methotrexate (MTX), the current “gold standard” treatment for collagen-induced arthritis (CIA). This study developed a highly efficient, cost-effective, and easy-to-operate system for the lab-scale production of endotoxin-free supercoiled plasmids with high quality and high yield. Based on optimised fermentation culture, we obtained a high yield of pcDNA-CCOL2A1 vaccine by PEG/MgCl2 precipitation and TRION-114. We then established a method for quality control of the pcDNA-CCOL2A1 vaccine. Collagen-induced arthritis (CIA) model rats were subjected to intramuscular injection of the pcDNA-CCOL2A1 vaccine (300 μg/kg) to test its biological activity.

Results
An average yield of 11.81 ± 1.03 mg purified supercoiled plasmid was obtained from 1 L of fermentation broth at 670.6 ± 57.42 mg/L, which was significantly higher than that obtained using anion exchange column chromatography and a commercial purification kit. Our supercoiled plasmid had high purity, biological activity, and yield, conforming to the international guidelines for DNA vaccines.

Conclusion
The proposed innovative downstream process for the pcDNA-CCOL2A1 vaccine can not only provide a large-scale high-quality supercoiled plasmid DNA for preclinical research but also facilitate further pilot-scale and even industrial-scale production of pcDNA-CCOL2A1 vaccine.
Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response
Authors: Smabers Lidwien P. , Wensink Emerens , Verissimo Carla S. , Koedoot Esmee , Pitsa Katerina-Chara , Huismans Maarten A. , Higuera Barón Celia , Doorn Mayke , Valkenburg-van Iersel Liselot B. , Cirkel Geert A. , Brousali Anneta , Overmeer René , Koopman Miriam , Braat Manon N. , Penning de Vries Bas , Elias Sjoerd G. , Vries Robert G. , Kranenburg Onno , Boj Sylvia F. , Roodhart Jeanine M. 
Published: February 2024

Abstract
Background
The inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard chemotherapies.

Methods
We optimized drug screen methods on 5–11 PDOs per condition of the complete set of 23 PDOs from patients treated for metastatic colorectal cancer (mCRC). PDOs were exposed to 5-fluorouracil (5-FU), irinotecan- and oxaliplatin-based chemotherapy. We compared medium with and without N-acetylcysteine (NAC), different readouts and different combination treatment set-ups to capture the strongest association with patient response. We expanded the screens using the optimized methods for all PDOs. Organoid sensitivity was correlated to the patient’s response, determined by % change in the size of target lesions. We assessed organoid sensitivity in relation to prior exposure to chemotherapy, mutational status and sidedness.

Results
Drug screen optimization involved excluding N-acetylcysteine from the medium and biphasic curve fitting for 5-FU & oxaliplatin combination screens. CellTiter-Glo measurements were comparable with CyQUANT and did not affect the correlation with patient response. Furthermore, the correlation improved with application of growth rate metrics, when 5-FU & oxaliplatin was screened in a ratio, and 5-FU & SN-38 using a fixed dose of SN-38. Area under the curve was the most robust drug response curve metric. After optimization, organoid and patient response showed a correlation coefficient of 0.58 for 5-FU (n = 6, 95% CI -0.44,0.95), 0.61 for irinotecan- (n = 10, 95% CI -0.03,0.90) and 0.60 for oxaliplatin-based chemotherapy (n = 11, 95% CI -0.01,0.88). Median progression-free survival of patients with resistant PDOs to oxaliplatin-based chemotherapy was significantly shorter than sensitive PDOs (3.3 vs 10.9 months, p = 0.007). Increased resistance to 5-FU in patients with prior exposure to 5-FU/capecitabine was adequately reflected in PDOs (p = 0.003).

Conclusions
Our study emphasizes the critical impact of the screening methods for determining correlation between PDO drug screens and mCRC patient outcomes. Our 5-step optimization strategy provides a basis for future research on the clinical utility of PDO screens.
ITC-net-audio-5: an audio streaming dataset for application identification in network traffic classification
Authors: Nikbakht Mohammad , Teimouri Mehdi 
Published: February 2024

Abstract
Objectives
An essential aspect of network traffic classification is application identification. This involves capturing and analyzing the traffic patterns of applications. There are a few publicly available datasets that specifically capture streaming data from network-based applications. Therefore, our objective is to generate an up-to-date dataset with a focus on audio streaming data. This dataset can be a valuable resource for identifying audio streaming applications in the field of network traffic classification.

Data description
The dataset contains network traffic captured during audio streaming communications on five trending applications: Google Meet, Skype, Telegram, WhatsApp, and SoundCloud. It includes 500 files in PCAP format captured by Wireshark and PCAPdroid tools during voice calls and online music playback. The concurrent utilization of these tools facilitates the avoidance of capturing background traffic.
Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury
Authors: Yin Zhiyuan , Ge Lingling , Cha Zhe , Gao Hui , A Luodan , Zeng Yuxiao , Huang Xiaona , Cheng Xuan , Yao Kai , Tao Zui , Xu Haiwei 
Published: February 2024

Abstract
Background
Unlike in lower vertebrates, Müller glia (MG) in adult mammalian retinas lack the ability to reprogram into neurons after retinal injury or degeneration and exhibit reactive gliosis instead. Whether a transition in MG cell fate from gliosis to reprogramming would help preserve photoreceptors is still under exploration.

Methods
A mouse model of retinitis pigmentosa (RP) was established using MG cell lineage tracing mice by intraperitoneal injection of sodium iodate (SI). The critical time point for the fate determination of MG gliosis was determined through immunohistochemical staining methods. Then, bulk-RNA and single-cell RNA seq techniques were used to elucidate the changes in RNA transcription of the retina and MG at that time point, and new genes that may determine the fate transition of MG were screened. Finally, the selected gene was specifically overexpressed in MG cells through adeno-associated viruses (AAV) in the mouse RP model. Bulk-RNA seq technique, immunohistochemical staining methods, and visual function testing were used to elucidate and validate the mechanism of new genes function on MG cell fate transition and retinal function.

Results
Here, we found the critical time point for MG gliosis fate determination was 3 days post SI injection. Hmga2 was screened out as a candidate regulator for the cell fate transition of MG. After retinal injury caused by SI, the Hmga2 protein is temporarily and lowly expressed in MG cells. Overexpression of Hmga2 in MG down-regulated glial cell related genes and up-regulated photoreceptor related genes. Besides, overexpressing Hmga2 exclusively to MG reduced MG gliosis, made MG obtain cone’s marker, and retained visual function in mice with acute retinal injury.

Conclusion
Our results suggested the unique reprogramming properties of Hmga2 in regulating the fate transition of MG and neuroprotective effects on the retina with acute injury. This work uncovers the reprogramming ability of epigenetic factors in MG.
Preventing lipophilic aggregation in cosolvent molecular dynamics simulations with hydrophobic probes using Plumed Automatic Restraining Tool (PART)
Authors: Beyens Olivier , De Winter Hans 
Published: February 2024

AbstractCosolvent molecular dynamics (MD) simulations are molecular dynamics simulations used to identify preferable locations of small organic fragments on a protein target. Most cosolvent molecular dynamics workflows make use of only water-soluble fragments, as hydrophobic fragments would cause lipophilic aggregation. To date the two approaches that allow usage of hydrophobic cosolvent molecules are to use a low (0.2 M) concentration of hydrophobic probes, with the disadvantage of a lower sampling speed, or to use force field modifications, with the disadvantage of a difficult and inflexible setup procedure. Here we present a third alternative, that does not suffer from low sampling speed nor from cumbersome preparation procedures. We have built an easy-to-use open source command line tool PART (Plumed Automatic Restraining Tool) to generate a PLUMED file handling all intermolecular restraints to prevent lipophilic aggregation. We have compared restrained and unrestrained cosolvent MD simulations, showing that restraints are necessary to prevent lipophilic aggregation at hydrophobic probe concentrations of 0.5 M. Furthermore, we benchmarked PART generated restraints on a test set of four proteins (Factor-Xa, HIV protease, P38 MAP kinase and RNase A), showing that cosolvent MD with PART generated restraints qualitatively reproduces binding features of cocrystallised ligands.
Asymmetric division of stem cells and its cancer relevance
Authors: Chao Shanshan , Yan Huiwen , Bu Pengcheng 
Published: February 2024

AbstractAsymmetric division is a fundamental process for generating cell diversity and maintaining the stem cell population. During asymmetric division, proteins, organelles, and even RNA are distributed unequally between the two daughter cells, determining their distinct cell fates. The mechanisms orchestrating this process are extremely complex. Dysregulation of asymmetric division can potentially trigger cancer progression. Cancer stem cells, in particular, undergo asymmetric division, leading to intra-tumoral heterogeneity, which contributes to treatment refractoriness. In this review, we delve into the cellular and molecular mechanisms that govern asymmetric division and explore its relevance to tumorigenesis.
Pharmacokinetics and bioequivalence evaluation of two oral formulations of cotrimoxazole tablets in healthy Chinese volunteers under fasting conditions
Authors: Zuo Xu , Zhao Xin , Shi Jinjin , Zhang Tiandong 
Published: February 2024

AbstractThis bioequivalence study was conducted to evaluate two oral formulations of cotrimoxazole tablets in healthy Chinese subjects. All 26 subjects recruited to this study were randomly and evenly classified into two groups and received a single dose (sulfamethoxazole: 400 mg and trimethoprim: 80 mg) of test cotrimoxazole tablets (generic drug) or reference cotrimoxazole tablets (branded drug). After a 7-day washout period, these subjects received one dose of reference drug or test drug. Blood samples were collected from participants before and up to 48 h after dosing to assess the concentration of sulfamethoxazole (SMX) and trimethoprim (TMP) in plasma and a plasma concentration-time curve was drawn. Then, the pharmacokinetics parameters were calculated accordingly. Our data revealed that there were no significant differences observed in the maximum plasma concentration (Cmax), area under the curve from time 0 to the last measurable concentration (AUC0-t), and area under the curve from time 0 to infinity (AUC0-∞) between the two formulations. For SMX, the 90% confidence intervals (CI) of the geometric mean ratio for Cmax, AUC0-t, and AUC0-∞ were 104.03-113.92%, 100.46-103.70%, and 100.41-103.81%, respectively. Similarly, for Trimethoprim (TMP), the 90% CI ranged from 98.54 to 106.95% for Cmax, from 99.31 to 107.68% for AUC0-t, and from 99.49 to 107.55% for AUC0-∞. Importantly, all these 90% CI values fell within the range of 80.00–125.00%, indicating that the test drug is bioequivalent to the reference drug. Furthermore, throughout the entire trial, no suspected serious adverse events were reported, indicating the safety profile of the newly developed generic cotrimoxazole. In summary, our study demonstrates that the newly developed generic formulation of cotrimoxazole is bioequivalent to the branded formulation under fasting conditions.
Exploring graphene structure, material properties, and electrochemical characteristics through laser-induced temperature analysis
Authors: Yang Na-Kyoung , Shin Yoo-Kyum , Park Saeyoung , Kim Sang-Min , Koo Bon-Jae , Jeong Joonsoo , Seo Min-Ho 
Published: February 2024

AbstractLaser-induced graphene (LIG) is a three-dimensional graphene structure fabricated through the irradiation of a polymer substrate with laser energy (or fluence, equivalently). This methodology offers a cost-effective and facile means of producing 3D nanostructures, yielding graphene materials characterized by extremely high surface area and superior electrical properties, rendering them advantageous for various electrochemical applications. Nonetheless, it is imperative to acknowledge that the structures and material properties of LIG are subject to substantial variations contingent upon processing parameters, thereby underscoring the necessity for systematic inquiry and systematic comprehension of processing conditions, such as fluence and multi-passing, and resultant outcomes. Herein, we explored the impact of different laser fluence levels on the structural and material properties of LIG. We, especially, focused on how laser fluence affected substrate temperature and found that it caused polyimide (PI) substrate pyrolysis, resulting in changes in 3D structures and material density to LIG properties. We also investigated the effects of a multi-passing process on 3D LIG structures and material qualities, varying fluences, and temperature fluctuations. Lastly, we assessed electrochemical properties using LIGs produced under different conditions as working electrodes, leading to distinct impedance profiles and cyclic voltammetry (CV) curves. These variations were linked to the unique structural and material characteristics of the LIG samples.
Rethinking our world: a perspective on a cleaner globe emerging from reduced anthropogenic activities
Authors: Nguyen Kim-Anh , Liou Yuei-An 
Published: February 2024

AbstractStringent measures, such as lockdowns, were implemented to curb the virus's spread, leading to reduced pollution levels and environmental improvements at various geographic scales, from cities to regions and nations. Such positive effects have been found and reported for regional scales, but not for a global scale till nowadays. This study aims to fill the gap by uncovering the modifications of global spatiotemporal eco-environmental vulnerability patterns between pre-pandemic (2016) and amid-pandemic (2020) periods. By analyzing various factors influencing the eco-environmental health or geo-health, such as human activities, climate change, and ecological dynamics, we seek to understand the intricate relationships and dynamics within these influential factors. We examined six categories of environmental vulnerability, which encompassed socioeconomics, land resources, natural hazards, hydrometeorology, and topography, using a five-dimensional stressor framework. Our analysis revealed a significant decrease in vulnerability levels across all categories, except for the very low level increased by 78.5% globally. These findings emphasize the detrimental impact of human activities on the global environment. They underscore the urgency of implementing spatial management strategies that prioritize sustainable geo-health development and foster a more resilient Earth.
Knee Biomechanics During Neurocognitively Challenged Drop Landings in Male Elite Soccer Players with Anterior Cruciate Ligament Reconstruction
Authors: Gholipour Aghdam Ghazal Mohammad , Alizadeh Mohammad Hossein , Minoonejad Hooman , Shirzad Elham , Wilke Jan 
Published: February 2024

Abstract
Background
Reactive decision-making during athletic movement has been demonstrated to evoke unfavorable biomechanics associated with anterior cruciate ligament (ACL) rupture. However, the current evidence is based on assessments of healthy individuals. We aimed to investigate unplanned jump landing kinetics and knee kinematics in ACL-reconstructed (ACLR) and non-injured athletes.

Methods
A total of 30 male professional soccer players (n = 15 ACLR after return to play, n = 15 matched controls) performed six drop landings onto a force plate. As a neurocognitive challenge requiring decision-making, a diode flashing in randomly selected colors indicated the requested landing location. Knee joint kinematics (flexion, valgus and tibial rotation angles) assessed with a 10-camera motion capture system, vertical ground reaction force (vGRF), time to stabilization (TTS) and length of the center of pressure (COP) trace (all analyzed from force plate data) were calculated. Cognitive function was assessed using the CNS Vital Signs battery.

Results
The ACLR group produced lower knee flexion angles than the control group (median [interquartile range] 50.00° [6.60] vs. 55.20° [4.45], p = .02). In addition, path length of the center of pressure (379 mm [56.20] vs. 344 mm [37.00], p = .04) and ground reaction force (3.21 N/kg [0.66] vs. 2.87 N/kg [0.48], p = .01) were higher for the ACLR group. No differences were found for knee valgus (p = .96), tibial rotation (p = .83) and TTS (p = .82). ACLR participants scored lower for reaction time (p = .02) and processing speed (p = .01). Unfavorable knee biomechanics were more often related to cognitive function in the ACLR group than in the control group (p < .05).

Conclusions
Impaired reactive decision-making during athletic movement may contribute to the high re-injury risk in individuals with ACLR. Prospective studies confirming potential cause-effect relationships are warranted.
Protocol for a single-arm, pilot trial of creatine monohydrate supplementation in patients with Alzheimer’s disease
Authors: Taylor Matthew K. , Burns Jeffrey M. , Choi In-Young , Herda Trent J. , Lee Phil , Smith Aaron N. , Sullivan Debra K. , Swerdlow Russell H. , Wilkins Heather M. 
Published: February 2024

Abstract
Background
Impaired brain bioenergetics is a pathological hallmark of Alzheimer’s disease (AD) and is a compelling target for AD treatment. Patients with AD exhibit dysfunction in the brain creatine (Cr) system, which is integral in maintaining bioenergetic flux. Recent studies in AD mouse models suggest Cr supplementation improves brain mitochondrial function and may be protective of AD peptide pathology and cognition.

Aims
The Creatine to Augment Bioenergetics in Alzheimer’s disease (CABA) study is designed to primarily assess the feasibility of supplementation with 20 g/day of creatine monohydrate (CrM) in patients with cognitive impairment due to AD. Secondary aims are designed to generate preliminary data investigating changes in brain Cr levels, cognition, peripheral and brain mitochondrial function, and muscle strength and size.

Methods
CABA is an 8-week, single-arm pilot study that will recruit 20 patients with cognitive impairment due to AD. Participants attend five in-person study visits: two visits at baseline to conduct screening and baseline assessments, a 4-week visit, and two 8-week visits. Outcomes assessment includes recruitment, retention, and compliance, cognitive testing, magnetic resonance spectroscopy of brain metabolites, platelet and lymphocyte mitochondrial function, and muscle strength and morphology at baseline and 8 weeks.

Discussion
CABA is the first study to investigate CrM as a potential treatment in patients with AD. The pilot data generated by this study are pertinent to inform the design of future large-scale efficacy trials.

Trial registration
ClinicalTrials.gov, NCT05383833, registered on 20 May 2022.