bluuebunny/crossref_metadata_2025_split huggingface dataset:
Road performance evaluation of prestressed high-strength concrete pile waste powder as alternative filler in asphalt concrete
Authors: Tu Botao , Yang Xinkui , Xu Shi , Zhao Zenggang , Zhou Yuheng , Jiang Jian , Fan Lulu , Tu Liangliang 
Published: November 2023

As a kind of solid waste, using Prestressed High-Strength Concrete Pile Waste Concrete (PPWC) as the replacement for limestone filler in asphalt concrete can not only reduce the accumulation of PPWC and increase its utilization but also avoid the increased road construction costs and environmental degradation associated with limestone mining. This study aims to investigate the effect of using PPWC filler to replace limestone filler on the road performance of asphalt concrete. Firstly, PPWC was ground into filler particles with a diameter less than 0.075 mm. The particle characteristics such as surface morphology, particle size distribution and chemical composition of PPWC filler and limestone filler were compared. Then, PPWC filler was used to replace limestone filler with different volume fractions to prepare asphalt concrete, and the water damage resistance, high-temperature rutting resistance, low-temperature crack resistance, fatigue resistance and adhesion performance of asphalt concrete were tested. The results showed that PPWC filler has a smaller particle size and rougher surface than limestone filler, and it contains Ca(OH)2 produced by hydration. The addition of PPWC filler can effectively improve the mechanical properties of asphalt concrete without reducing its water damage resistance. PPWC filler can improve the high-temperature rutting resistance and low-temperature crack resistance of asphalt concrete, but reduce its low-temperature fatigue resistance. The low content of PPWC filler will enhance the adhesion between asphalt mortar and aggregate. However, when the content of PPWC filler exceeds 50%, Ca (OH)2 in PPWC will reduce the adhesion between acid asphalt mortar and alkaline basalt aggregate. Therefore, the use of PPWC as filler in asphalt mixtures provides a reliable solution for the sustainable development of road materials.
Computational study of the motor neuron protein KIF5A to identify nsSNPs, bioactive compounds, and its key regulators
Authors: Kumar Rupesh , Madhavan Thirumurthy , Ponnusamy Kalaiarasan , Sohn Honglae , Haider Shazia 
Published: November 2023

Introduction: Kinesin family member 5A (KIF5A) is a motor neuron protein expressed in neurons and involved in anterograde transportation of organelles, proteins, and RNA. Variations in the KIF5A gene that interfere with axonal transport have emerged as a distinguishing feature in several neurodegenerative disorders, including hereditary spastic paraplegia (HSP10), Charcot-Marie-Tooth disease type 2 (CMT2), and Amyotrophic Lateral Sclerosis (ALS).Methods: In this study, we implemented a computational structural and systems biology approach to uncover the role of KIF5A in ALS. Using the computational structural biology method, we explored the role of non-synonymous Single Nucleotide Polymorphism (nsSNPs) in KIF5A. Further, to identify the potential inhibitory molecule against the highly destabilizing structure variant, we docked 24 plant-derived phytochemicals involved in ALS.Results: We found KIF5AS291F variant showed the most structure destabilizing behavior and the phytocompound “epigallocatechin gallate” showed the highest binding affinity (−9.0 Kcal/mol) as compared to wild KIF5A (−8.4 Kcal/mol). Further, with the systems biology approach, we constructed the KIF5A protein-protein interaction (PPI) network to identify the associated Kinesin Families (KIFs) proteins, modules, and their function. We also constructed a transcriptional and post-transcriptional regulatory network of KIF5A. With the network topological parameters of PPIN (Degree, Bottleneck, Closeness, and MNC) using CytoHubba and computational knock-out experiment using Network Analyzer, we found KIF1A, 5B, and 5C were the significant proteins. The functional modules were highly enriched with microtubule motor activity, chemical synaptic transmission in neurons, GTP binding, and GABA receptor activity. In regulatory network analysis, we found KIF5A post-transcriptionally down-regulated by miR-107 which is further transcriptionally up-regulated by four TFs (HIF1A, PPARA, SREBF1, and TP53) and down-regulated by three TFs (ZEB1, ZEB2, and LIN28A).Discussion: We concluded our study by finding a crucial variant of KIF5A and its potential therapeutic target (epigallocatechin gallate) and KIF5A associated significant genes with important regulators which could decrypt the novel therapeutics in ALS and other neurodegenerative diseases.
Advances on two serological assays for human papillomavirus provide insights on the reactivity of antibodies against a cross-neutralization epitope of the minor capsid protein L2
Authors: Mariz Filipe Colaco , Putzker Kerstin , Sehr Peter , Müller Martin 
Published: November 2023

IntroductionA second generation of prophylactic human papillomavirus (HPV) vaccines based on the minor capsid protein L2 has entered clinical trials as promising alternative to meet the gaps left out by the current vaccines concerning type-restricted protection, high costs and low penetrance in immunization programs of lowand middle-income countries. Most of the serological assays available to assess anti-HPV humoral responses are, however, not well suited for measuring vaccine-induced anti-L2 antibody responses.MethodsIn this work, we have advanced our automated, purely add-on High-Throughput Pseudovirion-Based Neutralization Assay (HT-PBNA) in an L2-oriented approach for measuring antibody-mediated neutralization of HPV types 6/16/18/31/33/52/58.Results and discussionWith the optimized settings, we observed 24- to 120-fold higher sensitivity for detection of neutralizing Ab to the L2 protein of HPV6, HPV16, HPV18, and HPV31, compared to the standard HT-PBNA. Alternatively, we have also developed a highly sensitive, cell-free, colorimetric L2-peptide capture ELISA for which the results were strongly concordant with those of the advanced neutralization assay, named HT-fc-PBNA. These two high-throughput scalable assays represent attractive approaches to determine antibody-based correlates of protection for the HPV L2 vaccines that are to come.
Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse
Authors: Moamin Mohammed Ridha , Allen Richard , Woods Steven Leslie , Brown Janet Elizabeth , Nunns Harry , Juncker-Jensen Anna , Lewis Claire Elizabeth 
Published: November 2023

IntroductionPatients with high-risk, triple negative breast cancer (TNBC) often receive neoadjuvant chemotherapy (NAC) alone or with immunotherapy. Various single-cell and spatially resolved techniques have demonstrated heterogeneity in the phenotype and distribution of macrophages and T cells in this form of breast cancer. Furthermore, recent studies in mice have implicated immune cells in perivascular (PV) areas of tumors in the regulation of metastasis and anti-tumor immunity. However, little is known of how the latter change during NAC in human TNBC or their impact on subsequent relapse, or the likely efficacy of immunotherapy given with or after NAC.MethodsWe have used multiplex immunofluorescence and AI-based image analysis to compare the immune landscape in untreated and NAC-treated human TNBCs. We quantified changes in the phenotype, distribution and intercellular contacts of subsets of tumor-associated macrophages (TAMs), CD4+ and CD8+ T cells, and regulatory T cells (Tregs) in PV and non-PV various areas of the stroma and tumor cell islands. These were compared in tumors from patients who had either developed metastases or were disease-free (DF) after a three-year follow up period.ResultsIn tumors from patients who remained DF after NAC, there was a marked increase in stromal CD163+ TAMs, especially those expressing the negative checkpoint regulator, T-cell immunoglobulin and mucin domain 3 (TIM-3). Whereas CD4+ T cells preferentially located to PV areas in the stroma of both untreated and NAC-treated tumors, specific subsets of TAMs and Tregs only did so only after NAC. Distinct subsets of CD4+ and CD8+ T cells formed PV clusters with CD163+ TAMs and Tregs. These were retained after NAC.DiscussionQuantification of stromal TIM-3+CD163+ TAMs in tumor residues after NAC may represent a new way of identifying patients at high risk of relapse. PV clustering of immune cells is highly likely to regulate the activation and function of T cells, and thus the efficacy of T cell-based immunotherapies administered with or after NAC.
Medical students on the COVID-19 frontline: a qualitative investigation of experiences of relief, stress, and mental health
Authors: Klasen Jennifer M. , Poljo Adisa , Sortino Rosita , Bogie Bryce J. M. , Schoenbaechler Zoe , Meienberg Andrea , Nickel Christian , Bingisser Roland , LaDonna Kori A. 
Published: November 2023

ObjectiveDuring the early stages of the COVID-19 pandemic, medical students were abruptly removed from clinical rotations and transitioned to virtual learning. This study investigates the impact of this shift on students’ wellbeing and preparedness for advanced training.MethodsThrough qualitative research methods, including semi-structured interviews, the experiences of medical students working on the COVID-19 frontline were explored.ResultsThe comprehensive findings of the study shed light on the profound emotional journey that medical students embarked upon during the relentless public health crisis. Within the chaos and overwhelming demands of the pandemic, medical students discovered a profound sense of purpose and fulfillment in their contributions to the welfare of the community. Despite the personal sacrifices they had to make, such as long hours, limited social interactions, and potentially risking their own health, students reported feelings of relief and gratitude.ConclusionTailored support systems for medical students’ wellbeing are crucial for improving healthcare delivery during crises. Medical schools should adopt a holistic curriculum approach, integrating interdisciplinary learning and prioritizing student wellbeing. Recognizing the pandemic’s impact on students and implementing targeted support measures ensures resilience and contributes to an improved healthcare system.
First insights into multidisciplinary and multispecialty long COVID networks—a SWOT analysis from the perspective of ambulatory health care professionals
Authors: Stengel Sandra , Gölz Lea , Kolb Joachim , Tarbet Karin , Völler Stefanie , Koetsenruijter Jan , Szecsenyi Joachim , Merle Uta 
Published: November 2023

IntroductionMultidisciplinary and multispecialty approaches with central integration of primary care, individualized long-term rehabilitative care, and multidisciplinary care pathways are recommended by international consortia to face the challenges of care of long COVID. Two regional long COVID networks—Rhein-Neckar (RN) and Ludwigsburg (LU) have emerged as ad hoc examples of best practice in Southern Germany. The aim of the community case study is to provide first insights into the experiences of the networks.MethodsThe exploratory observational study was conducted between April and June 2023, focusing on an observation period of just under 24 months and using a document analysis supported by MAXQDA and SWOT analysis with ambulatory health care professionals in two online group discussions.ResultsThe document analysis revealed that both networks have defined network participants who have agreed on common goals and patient pathways and have established ways of communicating, organizing, and collaborating. Both networks agreed on a primary care-based, multidisciplinary and multispecialty approach. The main differences in realization emerged in LU as a focus on the ambulatory setting and very concrete application to individual patients, while RN showed a focus on an intersectoral character with participation of the specialized university hospital sector, knowledge transfer and a supra-regional approach with the involvement of the meso and macro level. The SWOT analysis (n = 14 participants, n = 6 male, 7 physicians (4 disciplines), 7 therapists (5 professions)) showed strengths such as resulting collaboration, contribution to knowledge transfer, and improvement of care for individual patients. As barriers, e.g., lack of reimbursement, high efforts of care, and persistent motivation gaps became apparent. Potentials mentioned were, e.g., transferability to other diseases such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, promotion of addressing a “difficult topic” and promotion of intersectoral care concepts; risks mentioned were, e.g., limited network resources and negative effects on the development of other structures.ConclusionResulting implications for practice and research address a call to policy makers and funders to support further research to find out what generalizable results regarding usefulness, effectiveness, and efficiency including transferability to other post-infectious diseases can be derived.
Association of direct bilirubin to total bilirubin ratio with 90-day mortality in patients with acute-on-chronic liver failure
Authors: Ma Yuanji , Du Lingyao , Zhou Shaoqun , Bai Lang , Tang Hong 
Published: November 2023

BackgroundHyperbilirubinemia occurs when the liver fails to process bilirubin properly. A disproportionate increase in direct bilirubin indicates a decreased ability of the hepatocytes to uptake and/or convert bilirubin, which may impact the prognosis of patients with acute-on-chronic liver failure (ACLF). However, the association of direct bilirubin to total bilirubin ratio (DB/TB) with outcomes in patients with ACLF remains unclear.MethodsA retrospective study was conducted in West China Hospital of Sichuan University to assess the association between DB/TB and 90-day mortality in patients with ACLF. The diagnosis of ACLF was based on the Chinese Group on the Study of Severe Hepatitis B (COSSH) ACLF criteria. Ordinal logistic regression models, linear regression models, and Cox proportional hazards models were applied to evaluate the association between DB/TB and hepatic encephalopathy, disease severity, and outcome, respectively.ResultsA total of 258 patients with ACLF were included. The surviving patients were less likely to have liver cirrhosis and comorbidities, and their disease severities were milder than the dead. DB/TB was negatively correlated to cerebral score for hepatic encephalopathy (adjusted odds ratio: 0.01, p = 0.043), and disease severity (adjusted standardized coefficients: −0.42~−0.31, all p &lt; 0.001), respectively. A significant 90-day mortality risk of DB/TB was observed [all adjusted hazard ratio (aHR) &lt; 0.20 and all p ≤ 0.001]. Compared with patients with DB/TB &lt; 0.80, patients with ACLF and DB/TB ≥ 0.80 had much lower 90-day mortality risk (all aHR &lt; 0.75 and all p &lt; 0.01).ConclusionDB/TB could be an independent risk factor to predict the short-term prognosis in patients with ACLF. More attention should be paid to patients with lower DB/TB due to their poorer prognosis and more urgent need for liver transplantation.Clinical trial registration:http://www.chictr.org.cn/showproj.aspx?proj=56960, identifier, ChiCTR2000035013.
Composition, antibiotic resistance, and virulence analysis of microbiota in dormitory drain pipes
Authors: Hu Yan , Zhang Kunyuan , Li Nan , Wang Shengqin 
Published: November 2023

IntroductionDormitory washbasins can breed microorganisms that produce odorous gases, polluting the indoor environment.MethodsWe utilized metagenome sequencing to analyze the microbiota of 40 samples from the drain pipes of dormitory washbasins. Our study aimed to investigate the microbial community structure, antibiotic resistance genes, and virulence factors, and to identify potential influencing factors such as gender, hometown, frequency of hand sanitizer usage, and number of dormitory residents.ResultsThe analysis revealed 12 phyla and 147 genera, with Proteobacteria and Actinobacteria being the dominant phyla, and Mycobacterium and Nakamurella being the dominant genera. We found that the factors influencing the microbial community structure of the dormitory washbasin drain pipe are complex. The investigated factors have a slight influence on the drain pipe microbial community, with gender exerting a discernible influence. The annotation results revealed the presence of various virulence factors, pathogenic toxins and antibiotic resistance genes, including 246 different toxin types and 30 different types of antibiotic resistance genes. In contrast to the observed differences in microbial composition among samples, the distribution of resistance genes shows relatively small changes among samples. Antibiotics should be a contributing factor in the overall increase of antibiotic resistance genes in drain pipes.DiscussionOverall, our study provides important insights into the community structure and function of microorganisms in dormitory drainage systems, and can guide efforts to prevent and control microbial pollution.
DNA methylation of the oxytocin receptor interacts with age to impact neural response to social stimuli
Authors: Puglia Meghan H. , Lynch Morgan E. , Nance Madelyn G. , Connelly Jessica J. , Morris James P. 
Published: November 2023

IntroductionSocial isolation is one of the strongest predictors of increased risk of mortality in older adulthood. The ability to form and maintain the social relationships that mitigate this risk is partially regulated by the oxytocinergic system and one’s ability to attend to and process social information. We have previously shown that an epigenetic change to the DNA of the oxytocin receptor gene (OXTR methylation) affects the salience of social information in young adults. Little is known about how the oxytocinergic system ages and what effect this aging system has on social cognitive abilities throughout the lifespan.MethodsHere we explored age-related differences in the association between neural response during selective social attention and OXTR DNA methylation in young (age 18–31) and older (age 58-81) adults. Participants underwent fMRI during a selective social attention task and provided a DNA sample for the assessment of OXTR methylation.Results and DiscussionWe found that older adults activated diffuse areas of visual cortex and dorsolateral prefrontal cortex during selective social attention, consistent with the dedifferentiation and compensatory neural activation commonly reported in aging. We found a significant age-by-OXTR methylation interaction on neural response when attending to social stimuli in a complex display; young adults displayed a positive association between OXTR methylation and neural activation, replicating our prior finding that young adults with presumed diminished endogenous access to oxytocin recruit regions of the attentional cortex to a greater extent. This association did not hold for older adults. Instead, perceived social support interacted with OXTR methylation to influence neural response during selective social attention. These data suggest that environmental factors like social support moderate biological processes in aging and highlight the importance of a lifespan perspective for understanding associations between individual differences in the oxytocinergic system, neural function, and social behavior.
Active contact proximity to the cerebellothalamic tract predicts initial therapeutic current requirement with DBS for ET: an application of 7T MRI
Authors: Ikramuddin Salman S. , Brinda Annemarie K. , Butler Rebecca D. , Hill Meghan E. , Dharnipragada Rajiv , Aman Joshua E. , Schrock Lauren E. , Cooper Scott E. , Palnitkar Tara , Patriat Rémi , Harel Noam , Vitek Jerrold L. , Johnson Matthew D. 
Published: November 2023

ObjectiveTo characterize how the proximity of deep brain stimulation (DBS) active contact locations relative to the cerebellothalamic tract (CTT) affect clinical outcomes in patients with essential tremor (ET).BackgroundDBS is an effective treatment for refractory ET. However, the role of the CTT in mediating the effect of DBS for ET is not well characterized. 7-Tesla (T) MRI-derived tractography provides a means to measure the distance between the active contact and the CTT more precisely.MethodsA retrospective review was conducted of 12 brain hemispheres in 7 patients at a single center who underwent 7T MRI prior to ventral intermediate nucleus (VIM) DBS lead placement for ET following failed medical management. 7T-derived diffusion tractography imaging was used to identify the CTT and was merged with the post-operative CT to calculate the Euclidean distance from the active contact to the CTT. We collected optimized stimulation parameters at initial programing, 1- and 2-year follow up, as well as a baseline and postoperative Fahn-Tolosa-Marin (FTM) scores.ResultsThe therapeutic DBS current mean (SD) across implants was 1.8 mA (1.8) at initial programming, 2.5 mA (0.6) at 1 year, and 2.9 mA (1.1) at 2-year follow up. Proximity of the clinically-optimized active contact to the CTT was 3.1 mm (1.2), which correlated with lower current requirements at the time of initial programming (R2 = 0.458, p = 0.009), but not at the 1- and 2-year follow up visits. Subjects achieved mean (SD) improvement in tremor control of 77.9% (14.5) at mean follow-up time of 22.2 (18.9) months. Active contact distance to the CTT did not predict post-operative tremor control at the time of the longer term clinical follow up (R2 = -0.073, p = 0.58).ConclusionActive DBS contact proximity to the CTT was associated with lower therapeutic current requirement following DBS surgery for ET, but therapeutic current was increased over time. Distance to CTT did not predict the need for increased current over time, or longer term post-operative tremor control in this cohort. Further study is needed to characterize the role of the CTT in long-term DBS outcomes.
Outcomes of fertility preservation treatments in patients with endometrial cancer with different molecular classifications based on an NGS panel
Authors: Xu Yan , Zhao Mingming , Zhang Li , Wang Tianyou , Wang Bo , Xue Yu , Xu Zhiying , Shao Wenyu , Chen Xiaojun , Wang Chao 
Published: November 2023

BackgroundThe molecular classification of endometrial cancer has previously been shown to be associated with clinical outcomes. However, there are insufficient data to support the routine use of molecular classification for the treatment of patients seeking fertility preservation.MethodsHere, we retrospectively investigated 90 patients received fertility-sparing treatment. We used a next generation sequencing (NGS) panel to classify these patients into four subtypes. All patients received hormonal therapy combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every three months during the treatment.ResultsPatients with POLE mutations had the highest disease progression rate (50.0%, P=0.013), while the microsatellite instability-high (MSI-H) group had the highest recurrence rate (50.0%, P=0.042). PIK3CA mutation (hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.37–0.99; P=0.046), overweight (HR: 0.56; 95% CI: 0.32–0.96; P=0.033) and obesity (HR: 0.44; 95% CI: 0.20–0.95; P=0.036) were associated with a significantly lower cumulative complete response (CR) rate. The combination of gonadotropin-releasing hormone analogues (GnRH-a) and letrozole (HR: 3.43; 95% CI: 1.81–6.52; P&lt; 0.001) was associated with a significantly higher cumulative CR rate. KRAS mutation was significantly associated with disease progression (P=0.002). In wild-type TP53 patients, PTEN and PIK3CA mutations significantly prolonged the duration of treatment to achieve CR (log rank P=0.034; P=0.018).ConclusionThe implementation of molecular classification for EC patients undergoing fertility-sparing treatment is promising and can facilitate the selection of appropriate medical regimes to achieve better outcomes in patients with EC who require fertility preservation treatment.