bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total Neoadjuvant Therapy with Short-course Radiotherapy versus Long-course Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer, Korean trial (TV- LARK trial): study protocol of a multicentre randomized controlled trial
Authors: Kim Min Jung , Lee Dae Won , Kang Hyun Cheol , Park Ji Won , Ryoo Seung-Bum , Han Sae-Won , Kim Kyung Su , Chie Eui Kyu , Oh Jae Hwan , Jeong Woon Kyung , Kim Byoung Hyuck , Nam Eun Mi , Jeong Seung-Yong 
Published: July 2023

Abstract
Background
For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC.
Methods
This is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2–4 weeks in the TNT group and 6–10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate.
Discussion
The TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients.
Trial registration:
cris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.
MLST-FENet: Network traffic classification based on multilevel spatiotemporal feature fusion enhancement
Authors: Zhang Yu , Yu Xuecheng , Huang Yan , Zhang Xiaoyan , Jia Zhenhong , Qin Xizhong 
Published: July 2023

Abstract
Network traffic classification is an important task for ensuring network security and managing resources. The existing solution strategies are based on predefined features extracted by experts, which leads to high uncertainty when applied to network traffic classification. At the same time, it is necessary to continuously update features, making it difficult to achieve model migration and application. In contrast, in this study, a novel deep learning-based method was proposed to accurately determine network traffic characteristics. First, the traffic data were transformed into image data with texture features. Then, based on the characteristics of the input data, we proposed a multitask classification model for malicious and encrypted traffic called the multilevel spatiotemporal feature fusion enhanced network traffic classification model (MLST-FENet). This model automatically learns the nonlinear relationship between input and output and is an end-to-end framework. Experiments showed that MLST-FENet achieves better detection and classification performance for malicious and encrypted traffic on the USTC-TFC2016 and ISCX VPN -NONVPN datasets and has strong generalization ability, so it can be used in many practical application scenarios, providing more valuable information for the field of network security.
Protective efficacies of multi-epitope DNA subunit vaccine constructed from common antigens of Eimeria species in chickens
Authors: Chen Chen , Su Junzhi , Lu Mingmin , Xu Lixin , Yan Ruofeng , Li Xiangrui , Song Xiaokai 
Published: July 2023

Abstract
Clinical avian coccidiosis is typically caused by co-infection with several Eimeria species. Recombinant protein and DNA vaccines have shown promising prospects in controlling coccidiosis. On this basis, DNA vaccines that encode multiple epitopes from different Eimeria species may provide broad protection against co-infections. In this study, we designed a fusion gene fragment, 14EGT, that contained concentrated T-cell epitopes from four common antigens of Eimeria species (14-3-3, elongation factor 2, glyceraldehyde-3-phosphate dehydrogenase, and transhydrogenase). Multi-epitope DNA vaccine pVAX1-14EGT and recombinant protein vaccine pET-32a-14EGT (r14EGT) were then created based on the 14EGT fragment. Subsequently, cellular and humoral immune responses were measured in vaccinated chickens. Vaccination-challenge trials were also conducted, where the birds were vaccinated with the 14EGT preparations and later exposed to single or multiple Eimeria species to evaluate the protective efficacy of the vaccines. According to the results, vaccination with 14EGT preparations effectively upregulated the proportions of CD4+ and CD8+ T cells and the levels of Th1 and Th2 hallmark cytokines. The levels of serum IgG antibodies were also significantly increased. Animal vaccination trials revealed the alleviated enteric lesions, weight loss, and oocysts output compared to the control groups. The preparations were found to be moderately effective against single Eimeria species, with the anticoccidial index (ACI) ranging from 160 to 180. However, when challenged with multiple Eimeria species, the protection provided by the 14EGT preparations was not satisfactory, with ACI of 142.18 and 146.41, respectively. Collectively, the results suggest that a multi-epitope vaccine that encodes the T-cell epitopes of common antigens derived from Eimeria parasites could be a potential and effective strategy to control avian coccidiosis.
Potentiating humoral and cellular immunity using a novel hybrid polymer-lipid nanoparticle adjuvant for HBsAg-VLP vaccine
Authors: Liu Xuhan , Min Qiuxia , Song Huiping , Yue Aochun , Li Qin , Zhou Qing , Han Wei 
Published: July 2023

Abstract
Aluminum adjuvants are commonly used in vaccines to stimulate the immune system, but they have limited ability to promote cellular immunity which is necessary for clearing viral infections like hepatitis B. Current adjuvants that do promote cellular immunity often have undesired side effects due to the immunostimulants they contain. In this study, a hybrid polymer lipid nanoparticle (HPLNP) was developed as an efficient adjuvant for the hepatitis B surface antigen (HBsAg) virus-like particle (VLP) vaccine to potentiate both humoral and cellular immunity. The HPLNP is composed of FDA approved polyethylene glycol-b-poly (L-lactic acid) (PEG-PLLA) polymer and cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and can be easily prepared by a one-step method. The cationic optimised vaccine formulation HBsAg/HPLNP (w/w = 1/600) can maximise the cell uptake of the antigen due to the electrostatic adsorption between the vaccine nanoparticle and the cell membrane of antigen-presenting cells. The HPLNP prolonged the retention of the antigen at the injection site and enhanced the lymph node drainage of antigen, resulting in a higher concentration of serum anti-HBsAg IgG compared to the HBsAg group or the HBsAg/Al group after the boost immunisation in mice. The HPLNP also promoted a strong Th1-driven immune response, as demonstrated by the significantly improved IgG2a/IgG1 ratio, increased production of IFN-γ, and activation of CD4 + and CD8 + T cells in the spleen and lymph nodes. Importantly, the HPLNP demonstrated no systemic toxicity during immunisation. The advantages of the HPLNP, including good biocompatibility, easy preparation, low cost, and its ability to enhance both humoral and cellular immune responses, suggest its suitability as an efficient adjuvant for protein-based vaccines such as HBsAg-VLP. These findings highlight the promising potential of the HPLNP as an HBV vaccine adjuvant, offering an alternative to aluminum adjuvants currently used in vaccines.
WearNControl: Textile-Based Multimodal Customizable Activators
Authors: Sakif Mustasin Mahmood , Ihalainen Tiina , Merilampi Sari , Raumonen Pasi , Vuohijoki Tiina , Virkki Johanna 
Published: July 2023

Abstract
This paper presents early prototypes of WearNControl, textile-based multimodal customizable activators. The prototypes were targeted at turning our ordinary clothing and accessories assistive. The activators are part of a system with a web-based interface that allows the user to tailor the functionalities of the activators. These first prototypes can be activated by three different methods; pushing, touching, and pulling, and the interface allows the following functionalities: sending text messages and emails, making phone calls, and playing music. Based on preliminary prototype testing and system evaluation by five testers, an overall success rate of 98% was achieved for all activator inputs and text message outputs. Next, more types of activator prototypes will be created, and user opinions will be gathered for desired activator functionalities. Further, by using better servers and services, optimal system performance can be achieved.
Blockade of OX40/OX40L signaling using anti-OX40L delays disease progression in murine lupus
Authors: Zhao Junpeng , Li Liming , Feng Xiwei , Zhao Ming , Yin Huiqi , Lu Qianjin 
Published: July 2023

Abstract
Objectives
OX40 ligand (OX40L) locus genetic variants have relationships with the risk for systemic lupus erythematosus (SLE), OX40L blockade has been shown to ameliorate renal damage and suppress autoantibody production in NZB/W F1 mice. However, it is unclear how OX40L blockade delays lupus phenotype.
Methods
In present study, we examined the impact of blocking OX40L using anti-OX40L in the MRL/lpr murine model of lupus. Mice were sorted into 3 groups with 9 ~ 11 mice per group as follows: IgG treatment, Cyclophosphamide (CTX) treatment, and anti-OX40L treatment. Treated mice were harvested, and samples of serum, kidney, and spleen were collected for outcome evaluation. Next, we investigated the impact of anti-OX40L on immunosuppression in KLH-immunized C57BL/6J mice aged 8 weeks through the detection of serum immunoglobulins (Igs) and splenocyte flow cytometry. In vitro treatment of anti-OX40L in CD4+ T and CD19+ B cells were used for exploring the roles of OX40L in SLE pathogenesis.
Results
Anti-OX40L delayed disease progression in MRL/lpr mice, accompanied by decreased production of anti-dsDNA, proteinuria, and Ig deposition in kidney, as well as lower frequencies of Th1 and Tfh cells in the spleen. Compared to the IgG group, anti-OX40L was found to up-regulate polyclonal CD4+ T cell differentiation into Tregs in vitro. In KLH-immunized mice, decreased levels of Igs, and plasmablast cells were observed in anti-OX40L group. Blocking OX40/OX40L signaling also inhibited TLR7-mediated differentiation of antibody secreting cells (ASCs) and production of antibody through the up-regulation of SPI-B, IRF8, and PAX5, and down-regulation of Xbp-1 in B cells in vitro.
Conclusion
Together, these results propose OX40L as a promising therapeutic target for SLE.
Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia
Authors: Ahmad Mostapha , Anillo Margarita Rosa Ríos , Lopez Johan E Acosta , Henriquez Martha L Cervantes , Banfi Martha Martinez , Halhusema Wilmar Pineda , Rozo Pedro Puentes , Barros Cristian Sanchez , Pinzon Andres , Patel Hardip , Velez Jorge I , Camacho Jose Luis Villarreal , Pineda David A , Burgos Mauricio Arcos , Rojas Manuel Sanchez 
Published: July 2023

Abstract
Background
The second world's most extensive cluster of patients affected with Huntington’s disease (HD), a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene, inhabits Juan de Acosta, a city located on the Caribbean coast of Colombia. This group represents the second most extensive pedigree clustering HD in the world.
Methods
We included 291 descendants of families living in Juan de Acosta, Colombia, who had at least one member with HD. Blood samples were obtained, and genomic DNA was extracted. The HTT CAG expansion was quantified using an amplicon sequencing protocol. Statistical and bioinformatic analyses were conducted using several modules implemented in R. Statistical threshold significance was set at P < 0.05.
Results
A total of 33 HD patients were analyzed, and a mean of 21.91 HTT CAG repeats with a standard deviation of 8.92 copies was obtained. The most affected individuals were adults, and the most common primary and secondary alleles were 17/7 and 17/10, respectively. Mosaicism increased with age in participants with HD, and slippage analyses revealed differences by HD allele type for the secondary allele, but no significant differences were observed by sex. Slippage tended to increase with the number of CAG repeats in participants with HD, but the increase was not statistically significant. The most common haplotype was 17/7_17/10.
Conclusion
This study analyzed the genetic and molecular features of HD by examining 291 participants, including 33 with HD. Mosaicism was found to increase with age in subjects with HD, particularly for the secondary allele; the most common haplotype was 17/7_17/10. Slippage for the secondary allele varied by HD allele type, but no significant difference in slippage was observed by sex. The findings offer valuable insights into the disease and could have implications for future research and clinical management.
Early warning of potential epidemics: A pilot application of an early warning tool to data from the pulmonary clinic of the university hospital of Thessaly, Greece
Authors: Meletis Eleftherios , Poulakida Irene , Perlepe Garyfallia , Katsea Asimina , Boutlas Stylianos , Papadamou Georgia , Gourgouliannis Konstantinos , Kostoulas Polychronis 
Published: July 2023

Abstract
This paper describes a pilot application of the Epidemic Volatility Index (EVI) to data from the pulmonary clinic of the University Hospital of Thessaly, Greece, for monitoring respiratory infections, COVID-19, and flu cases. EVI, a simple and easily implemented early warning method based on the volatility of newly reported cases, exhibited consistent and stable performance in detecting new waves of epidemics. The study highlights the importance of implementing early warning tools to address the effects of epidemics, including containment of outbreaks, timely intervention strategies, and resource allocation within real-world clinical settings as part of a broader public health strategy. The results presented in the figures demonstrate the association between successive early warnings and the onset of new waves, providing valuable insights for proactive decision-making. A web-based application enabling real-time monitoring and informed decision-making by healthcare professionals, public health officials, and policymakers was developed. This study emphasizes the significant role of early warning methods in managing epidemics and safeguarding public health. Future research may explore extensions and combinations of multiple warning systems for optimal outbreak interventions and application of the methods in the context of personalized medicine.
Intracerebral administration of a novel self-assembling peptide hydrogel is safe and supports cell proliferation in experimental intracerebral haemorrhage
Authors: Bolan Faye , Dickie Ben R , Cook James R , Thomas Josephine M , Pinteaux Emmanuel , Allan Stuart M , Saiani Alberto , Lawrence Catherine B 
Published: July 2023

Abstract
Intracerebral haemorrhage (ICH) is the deadliest form of stroke but current treatment options are limited, meaning ICH survivors are often left with life-changing disabilities. The significant unmet clinical need and socioeconomic burden of ICH means novel regenerative medicine approaches are gaining interest. To facilitate regeneration of the ICH lesion, injectable biomimetic hydrogels are proposed as both scaffolds for endogenous repair and delivery platforms for pro-regenerative therapies. In this paper, the objective was to explore whether injection of a novel self-assembling peptide hydrogel (SAPH) Alpha2 was feasible, safe and could stimulate brain tissue regeneration, in a collagenase-induced ICH model in rat. Alpha2 was administered intracerebrally at 7 days post ICH and functional outcome measures, histological markers of damage and repair and RNA-sequencing were investigated for up to 8 weeks. The hydrogel Alpha2 was safe, well-tolerated and was retained in the lesion for several weeks, where it allowed infiltration of host cells. The hydrogel had a largely neutral effect on functional outcomes and expression of angiogenic and neurogenic markers but led to increased numbers of proliferating cells. RNAseq and pathway analysis showed that ICH induced genes related to inflammatory and phagocytic pathways and these changes were also observed after administration of hydrogel. Overall, the results show that the novel hydrogel was safe when injected intracerebrally, had no negative effects on functional outcomes but increased cell proliferation. To elicit a regenerative effect, future studies could use a functionalised hydrogel or combine it with an adjunct therapy.
The attitude of Iranian directors and screenwriters toward patients with mental disorders in comparison with a general population group
Authors: Kamalinejad Kiandokht , Shariat Seved Vahid , Eissazade Negin , Shalbafan Mohammadreza 
Published: July 2023

Abstract
Background: Mental disorders are accountable for 16% of disability-adjusted life years (DALYs) worldwide. Therefore, accessible, cost-effective interventions are needed to help provide preventive and therapeutic options. As directors and screenwriters can reach a great audience, they can use their job to either promote stigma or educate the public with the correct definition and conception of mental disorders. Therefore, we aimed to measure the attitude of contemporary Iranian directors and screenwriters toward patients with mental disorders in comparison with a general population group. Methods: In this cross-sectional study we included 72 directors and screenwriters between 18-65 years old who had worked in at least one movie/television show, and 72 age- and education-matched controls. We collected the demographic data of the participants, and used the Persian version of the Level of Contact Report (LCR) to measure their familiarity with mental disorders, and used the Persian version of Social Distance Scale (SDS) and Dangerousness Scale (DS) to measure their attitude toward them.
Results: Compared to the general population group, directors and screenwriters had significantly lower SDS (12.51±3.8 vs. 13.65±3.73) and DS (12.51±3.8 vs. 13.65±3.73) scores (P<0.001), indicating a more positive attitude toward patients with mental disorders. Familiarity with mental disorders was not significantly different between the groups. Female gender was associated with a more negative attitude in the directors and screenwriters group. Additionally, among the SDS items, ‘How would you feel about someone with severe mental disorder marrying your children?’ and ‘How would you feel about someone with severe mental disorder taking care of your children for a couple of hours?’ received the most negative feedback in both groups. Among the DS items, ‘there should be a law forbidding a former mental patient the right to obtain a hunting license’ received the most negative feedback in both groups.
Conclusions: Directors and screenwriters had a more positive attitude toward patients with mental disorders. Due to this relatively positive attitude, this group of artists can potentially contribute to anti-stigma initiatives by offering educational materials and resources, promoting mental health care, and improving access to mental health care.
WITHDRAWN: TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin
Authors: Zhang Yu , Yuan Xiaoxue , Wang Jun , Han Ming , Lu Hongping , Wang Yun , Liu Shunai , Cheng Jun , Xing Huichun 
Published: July 2023

Abstract

Background
Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti-HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed.
Results
In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion-related molecules on HBV replication. The in-depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA-histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA-dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication.
Conclusions
These data suggest that TRPV4 exerts multifaceted HBV-related synergistic factors and may serve as a therapeutic target for CHB.
Ecopolyols from spent coffee grounds through acid liquefaction using polyol: Synthesis and its optimization
Authors: Paria Sarbaranjan , Kim Gyuri , Lee Jung Wook , Jeong Seongrok , Sahu Pranabesh , Park Sung Hwan , Oh Jeong Seok 
Published: July 2023

Abstract
Recently, colossal research interests have been paid in the scientific community to synthesize biomass-based polyols due to their availability, sustainability, and low toxicity. Here, in this work, the main objective involves an effective synthesis of bio-polyol from spent coffee ground through an acid-catalyzed liquefaction reaction by employing sulfuric acid and a mixed solvent of polyether polyol and glycerol at a reasonable reaction temperature. The effect of experimental liquefaction conditions on the extent of conversion was optimized by the design of experiments and statistical analysis using a 23-full-factorial design with temperature, time, and acid concentration as the process parameters. Also, the analysis of variance results with a 95% confidence level reveals that acid concentration is the most influencing factor on biomass conversion. However, the achieved maximum conversion was 65.3 wt% at 170°C, 120 min, and 4 wt% of catalyst. The prepared polyol at the optimized condition showed an acid value of 18.6 mg KOH/g polyol, a hydroxyl value of 77.9 mg KOH/g polyol, and a viscosity of 348.2 cPs at 25 ºC. Thus, this work demonstrates a promising and efficient approach to synthesize bio-based liquid polyols using acid liquefaction at a reasonable temperature.