bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-specific kinetics of neutralizing antibodies and infection enhancement among ≤1 year-old Indian infants
Authors: Chelluboina Shweta , Mishra Akhilesh Chandra , Arankalle Vidya Avinash , Shrivastava Shubham
Published: February 2025

Background

Infants born to dengue-immune mothers acquire maternal antibodies to dengue. Maternal antibodies decline over time, making infants susceptible to primary dengue infections. Another important concern is the role of maternal antibodies in causing antibody-dependent enhancement (ADE) during primary infections. In this study, we aimed to investigate the kinetics of dengue virus (DENV)-neutralizing antibodies and infection-enhancing activity in Indian infants.

Methods

Healthy infants at birth (cord blood), and at 3, 6, 9, and 12 months of age (n=32/group) were included in this cross-sectional study. Serum samples were tested for neutralizing antibodies using the foci-reduction neutralization test and enhancing antibodies using the ADE assay against DENV1-4 serotypes.

Results

Neutralizing antibody positivity declined with the increasing age of the infants. Undetectable levels of neutralizing antibodies to DENV1-4 serotypes were reported in 84% of infants by 9 months. Significantly lower neutralizing antibody titers were also reported in 9-month-old infants compared to that in 6-month-old infants and infants at birth. Comparable levels of enhancement of DENV1-4 infection at a particular dilution to at least one serotype were noted in infants at 3 and 6 months of age. Fold enhancement of DENV1-4 infection was found to be highest in 6-month-old infants at a dilution of 1:20. In summary, our data suggests that DENV infection–enhancing activity aligns with the decline of neutralizing antibodies.

Conclusion

Our study indicates that maternally acquired neutralizing antibodies could be protective until 6 months of age and capable of facilitating ADE on exposure to dengue infections in later months of life.
Impact of self-reported SARS-CoV-2 antibody positivity on cardiac structure and function: findings from UK Biobank CMR cohort
Authors: Liu Chang , Ma Yao , Qiao Shiyuan , Li Kexin , Qi Mengyao , Gu Chunyu , Zhang Lanxin , Wei Jia , Gao Dengfeng
Published: February 2025

Background

SARS-CoV-2 antibody positivity, whether due to natural infection or vaccination, is known to be associated with specific cardiac and vascular damage, yet its impact on cardiac structure and function in prospective cohorts remains incompletely understood.

Objective

We aimed to assess cardiac changes in the UK Biobank cohort among individuals with self-reported seropositive results for SARS-CoV-2 antibodies.

Methods

UK Biobank participants with self-reported serological results for SARS-CoV-2 antibodies, who underwent their first cardiac magnetic resonance (CMR) scan after 2019 were included. Cardiac changes potentially associated with SARS-CoV-2 antibody positivity were assessed, with measurements of left ventricular (LV) parameters, including volume, dimensions, wall thickness, myocardial mass, cardiac output (CO), and cardiac index (CI), manually extracted from the CMR images. Propensity score matching (PSM) was used to pair seropositive and seronegative individuals. Native T1 was used to assess the within-subject changes in seropositive individuals. Logistic regression was performed to assess the association between SARS-CoV-2 antibody status and the incidence of LV hypertrophy.

Results

A total of 720 participants were included, with 453 individuals self-reporting as SARS-CoV-2 antibody positive. After PSM, 261 participants remained in each group. Over an average follow-up period of 110 days, significant decreases in CO and CI were observed in the paired participants. Additionally, native T1 values appeared to be elevated in seropositive participants (852.77 ± 53.55 ms vs. 860.01 ± 47.81 ms, P = 0.012). Logistic regression analysis in the overall cohort indicated an association between SARS-CoV-2 antibody positivity and an increased risk of LV hypertrophy, with an adjusted odds ratio of 3.257 [95% CI (1.036–10.239), P = 0.043].

Conclusions

Our findings suggest subtle cardiac changes associated with SARS-CoV-2 antibody positivity within approximately hundred days. SARS-CoV-2 antibody positivity appeared to be associated with an increased risk of LV hypertrophy. However, these results are exploratory, and further longitudinal studies with extended follow-up are needed to better understand the long-term cardiac impact of SARS-CoV-2 antibody positivity.
Comparative effectiveness of exercise interventions on arterial stiffness in individuals at risk for cardiovascular disease: a systematic review and network meta-analysis
Authors: Wu Ruo-Shan , Zhang Yan , Yuan Xin-Wang , Yan Xin , Fu Xiao-Lei
Published: February 2025

Background

Previous studies have shown that exercise can improve arterial stiffness (AS). However, it remains unclear which type of exercise is most effective for managing AS, particularly in individuals at high risk for cardiovascular diseases (CVD). This review aims to evaluate the effects of various exercises on AS and related variables in individuals at high risk for CVD.

Methods

A comprehensive search strategy was employed to systematically explore MEDLINE (PubMed), Embase, Cochrane Library, EBSCOhost, and Web of Science to identify relevant studies. Inclusion criteria were: (1) randomized controlled trials; (2) participants with known CVD risk factors as per the American College of Sports Medicine guidelines; (3) interventions including interval training (INT), aerobic exercise (AE), resistance exercise, and combined exercise (CT); (4) control groups engaging in no intervention, routine care, or health education; (5) outcome measures of pulse wave velocity (PWV), systolic blood pressure (SBP), and diastolic blood pressure; and (6) studies published in English. Studies were assessed using the Cochrane risk of bias tool and analyzed with a random-effects network meta-analysis.

Results

The review included 2,034 participants from 43 studies. Both CT [standardized mean difference (SMD) = −0.98, p < 0.001, I2 = 84%] and INT (SMD = −0.77, p < 0.001, I2 = 61%) significantly reduced PWV, but both showed considerable heterogeneity. INT (SMD = −0.382, p < 0.001, I2 = 45%) and AE (SMD = −0.369, p < 0.001, I2 = 43%) significantly reduced SBP. Surface under the cumulative ranking curve (SUCRA) showed that CT (SUCRA = 87.2) was the most effective for lowering PWV, while INT (SUCRA = 81.3) was the most effective for lowering SBP.

Conclusion

In high-risk populations for CVD, CT was most effective in improving AS, while INT demonstrated the greatest reduction in SBP. AE showed greater benefits at moderate to low intensities. Due to significant heterogeneity in CT, its results should be interpreted with caution. Further research with larger sample sizes is needed to confirm these findings.
Using a wider digital ecosystem to improve self-regulated learning
Authors: Domino Molly , Shaffer Clifford A.
Published: February 2025

Introduction

Self-regulated learning skills are necessary for academic success. While not all students entering post-secondary education are proficient at many of these critical skills, they can be improved upon when practiced. However, self-regulation tends to be highly internal, making it difficult to measure. One form of measurement comes from using data traces collected from educational software. These allow researchers to make strong empirical inferences about a student's internal state. Automatically captured data traces also make it possible to provide automated interventions that help students practice and master self-regulated learning skills.

Methods/results

Using an experimental methodology we created a set of promising data traces that are grounded in theory to study self-regulated learning within a typical Computer Science course. Extra attention is given to studying the skill of help-seeking, which is both a key to success in CS and requires unobtrusive observation to properly measure.

Discussion

We also make the case for taking a broader perspective with our data collection efforts. The traces identified in this paper are not from one source, but the full ecosystem of software tools common to CS courses.
Nurturing bonds that empower learning: a systematic review of the significance of teacher-student relationship in education
Authors: Di Lisio Giulia , Milá Roa Antonio , Halty Amaia , Berástegui Ana , Couso Losada Alba , Pitillas Carlos
Published: February 2025

Background

Teachers are regarded as attachment-like figures, with positive and supportive teacher-student relationships (TSRs) being linked to improved academic performance and outcomes, while negative TSRs are associated with lower academic results. This systematic review aims to map the relational dimensions of the TSR and its impact on academic (dis)engagement, (under)achievement and early school leaving (ESL), focusing on Secure Base and Safe Haven attachment dimensions and the influence of vulnerability factors.

Methods

The review followed the PRISMA guidelines and included 45 empirical quantitative studies (2018–2022) sourced from Academic Search Complete, ERIC, Scopus and Web of Science. Inclusion criteria were English-written quantitative methodology studies, with TSR as the independent variable and academic outcomes as the dependent variable. Exclusion criteria included longitudinal designs, purely qualitative studies, correlational analyses, studies lacking key variables or presenting reversed relationships, those conducted in e-learning environments, university settings, extreme schooling conditions and non-English language studies. A descriptive and narrative style analysis was used to synthesize the results based on Safe Haven, Secure Base and Global dimensions.

Results and discussion

Key findings highlighted the significant role of TSR in influencing academic engagement, achievement, and ESL, particularly from vulnerable populations. The synthesis of results indicated that positive TSRs are associated with improved academic outcomes, while negative TSRs can exacerbate disengagement and underachievement. Limitations of the evidence included potential publication bias and the lack of quality control measures, as well as the exclusion of longitudinal and qualitative studies. The findings underscore the significance of a holistic understanding of the TSR in education, highlighting its multifaceted impact on student success and suggesting that future research should consider qualitative and longitudinal studies and expand the scope to studies in non-English language.
Implementing artificial intelligence in academic and administrative processes through responsible strategic leadership in the higher education institutions
Authors: Khairullah Suleman Ahmad , Harris Sheetal , Hadi Hassan Jalil , Sandhu Rida Anjum , Ahmad Naveed , Alshara Mohammed Ali
Published: February 2025

Artificial Intelligence (AI) has enormous potential to make a transformative impact in multiple fields. It has made significant strides in Higher Education by reshaping traditional administrative processes, learning, leadership, and teaching. This review explores the substantial impact of integrating AI in Higher Education Institutions (HEIs), from improving education delivery to enhancing student outcomes and streamlining administrative processes and strategic leadership. By catering to the diverse learning needs of students with the help of tools that directly affect academics, monitor student engagement and performance, and provide data-driven interventions, AI offers what the HEIs have long been waiting for to revolutionize the overall Higher Education landscape. This review also highlights that with AI's ability to streamline administrative tasks by enhancing admissions and enrolment processes, academic records management system, and financial aid and scholarships processes, AI not only facilitates improving the overall processes but also makes staff and faculty members focus less on mundane and monotonous tasks, hence concentrating more on the responsibilities and strategic initiatives that require focused attention. We identified that the key to unlocking the significant potential of AI is responsible strategic leadership. Strategic leadership requires aligning AI integration goals with the strategic mission of HEIs, fostering an environment ready to embrace innovation and ensuring that the required accountability and governance frameworks are in place for AI integration and usage. It is also the role of leadership to consider ethical considerations, collaborations with the relevant stakeholders, concerns about job displacement, and potential biases, ensuring that AI is used to its full potential for the benefit of faculty, staff, students, and society. We conclude the paper with AI-driven future implications, i.e., emerging technologies, continuous enhancement and AI-based enhanced research accomplishments.
The genomics of postglacial vicariance and freshwater adaptations in European subarctic threespine sticklebacks
Authors: Adhikari Dhurba , Karlsen Bård Ove , Jørgensen Tor Erik , Johansen Steinar Daae , Nordeide Jarle Tryti , Moum Truls Borg
Published: February 2025

Marine threespine sticklebacks (Gasterosteus aculeatus) have colonized numerous freshwater lakes since the last ice age. The loss of body armor, such as reduced pelvic spines and lateral plate numbers, is a recurrent feature upon freshwater colonization and is attributed to parallel evolution. This study examines genome-wide genetic diversity and differentiation among sticklebacks from a marine site and two freshwater lakes of the same watercourse in subarctic Europe. The upper lake is unique in that it harbors a population of polymorphic sticklebacks, some with fully developed and others with reduced pelvic structures. Our results based on deep sequencing of pooled population samples showed common signatures of selection for freshwater sticklebacks in certain parts of the genome, such as the Eda containing region, but also evidence of differential selection, and the presence of large chromosomal inversions that seem to play an essential role in stickleback evolution. Pelvic reduction in sticklebacks has previously been linked to deletions in the enhancers of the pituitary homeobox transcription factor gene (Pitx1). While the genetics of Pitx1 seem unable to fully explain pelvic spine polymorphism in this population, we found differentiation between spined and spineless sticklebacks in several genomic regions, which harbor genes that might be involved in pelvic development. Most significantly, genetic differentiation between spined and spineless sticklebacks was noted in a region of chromosome 9 where the gene Hand2, previously implicated in limb development, is located. Our findings suggest that pelvic reduction in these sticklebacks involves multiple genetic factors, indicating parallel evolution through polygenic influences.
Growth arrest and DNA damage-inducible 45: a new player on inflammatory diseases
Authors: Ma Yanmei , Hossen Md Munnaf , Huang Jennifer Jin , Yin Zhihua , Du Jing , Ye Zhizhong , Zeng Miaoyu , Huang Zhong
Published: February 2025

Growth arrest and DNA damage-inducible 45 (GADD45) proteins are critical stress sensors rapidly induced in response to genotoxic/physiological stress and regulate many cellular functions. Even though the primary function of the proteins is to block the cell cycle, inhibit cell proliferation, promote cell apoptosis, and repair DNA damage to cope with the damage caused by internal and external stress on the body, evidence has shown that GADD45 also has the function to modulate innate and adaptive immunity and plays a broader role in inflammatory and autoimmune diseases. In this review, we focus on the immunomodulatory role of GADD45 in inflammatory and autoimmune diseases. First, we describe the regulatory factors that affect the expression of GADD45. Then, we introduce its immunoregulatory roles on immune cells and the critical signaling pathways mediated by GADD45. Finally, we discuss its immunomodulatory effects in various inflammatory and autoimmune diseases.
Increased sputum peripheral helper T cells are associated with the severity of rheumatoid arthritis but not with the severity of airway disease
Authors: Yokoi Eito , Wakahara Keiko , Nakamura Saya , Fukutani Eriko , Asai Shuji , Takahashi Nobunori , Kojima Toshihisa , Iwano Shingo , Shimada Satoko , Chen-Yoshikawa Toyofumi Fengshi , Hashimoto Naozumi , Ishii Makoto
Published: February 2025

Objective

Peripheral helper T (Tph) cells, together with plasma cells, are the major pathogenic lymphocytes in the synovium in rheumatoid arthritis (RA). However, whether these cells are involved in RA-associated lung and/or airway disease is unknown.

Methods

Tph cells in sputum were analyzed by flow cytometry and compared with those in synovial fluid and synovial tissue. Forty RA subjects for whom induced sputum could be collected were analyzed along with sputum Tph cells and several clinical parameters; RA severity was assessed using the Disease Activity Score for 28 joints (DAS28). Lung and airway disease was assessed by chest computed tomography (CT), pulmonary function test, the chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), and sputum culture. Tph cells in the lung of RA subjects were analyzed using lung resection samples in a separate cohort.

Results

Tph cells were observed in the sputum, as well as the lung, synovial fluid, and synovial tissue of RA patients. Sputum Tph cells were increased in patients with airway disease. Among these patients, Tph cells were more frequent in those with high DAS28, high serum immunoglobulin G (IgG), and high sputum IgG. However, there was no association between Tph cells and the severity of airway disease as assessed by chest CT findings, lung function, CAT, and sputum culture.

Conclusions

Tph cells were increased in the airways as well as in the synovium in patients with RA. Airway Tph cells were associated with severity of RA but not with the severity of airway disease. Airway Tph cells may represent a novel target for disease management and treatment.
Yiqi Huayu Jiedu Decoction reduces colorectal cancer liver metastasis by promoting N1 neutrophil chemotaxis
Authors: Zhou Hua-Jian , Mu Bai-Xiang , Wen Meng-Chao , Zhao Qi , Li Yuanxiang , Zhao Wen-Xuan , Yin Hong-Ye , Ren Shuai , Zhou Jin-Yong , Chen Min
Published: February 2025

Objective

To observe the inhibitory effect and potential mechanism of Yiqi Huayu Jiedu Decoction (YHJD) on liver metastasis of colorectal cancer (CRC).

Methods

We compared the changes of liver weight and liver index before and after YHJD treatment in CRC liver metastasis mouse models. HE staining was employed to observe the pathological changes in mouse liver tissue sections. Flow cytometry was used to analyze the number and marker of neutrophils treated with YHJD. Transcriptomics, proteomics, and multiplex cytokine array analyses were conducted to further verify the role of YHJD on CXCL1. Differential gene analysis was performed to further explore the mechanism by which YHJD inhibits liver metastasis of CRC.

Results

Animal studies demonstrated that YHJD reduces liver metastases. Flow cytometry results revealed that YHJD promotes N1 neutrophils in liver. Combining multi-omics and multiple cytokine arrays, we observed a significant increase in the expression of CXCL1 in the liver and plasma. GO and KEGG enrichment analyses indicated that YHJD may regulate the chemotaxis of neutrophils to inhibit the liver metastasis of CRC by participating in the regulation of cell adhesion molecule binding, adhesion protein binding, and multiple metabolic pathways.

Conclusions

YHJD inhibits CRC liver metastasis by upregulating CXCL1, thereby promoting N1 neutrophil chemotaxis towards the liver, and concurrently raising the expression of N1 neutrophil markers.
Identification of B-cell epitopes of Indian Zika virus strains using immunoinformatics
Authors: Roy Rohan Raj , Tadkalkar Nitali , Deshpande Gururaj Rao , Atre Nitin M. , Shil Pratip , Sapkal Gajanan
Published: February 2025

Introduction

The Zika virus is an emerging Flavivirus known to cause Zika infection in humans. It is associated with severe health problems such as microcephaly and Guillain-Barré syndrome post the Brazilian epidemic in 2015-16. The spread of the Zika virus to the Asian subcontinent, especially to India is a matter of great concern. Two recent co-circulating Indian Zika virus strains such as Rajasthan and Maharashtra detected in 2018 and 2021 were studied to identify B-cell epitopes in the envelope and non-structural 1 protein as these epitopes are major indicators of robust humoral immune response. The study aimed at identifying novel epitopes, followed by molecular docking with potent Zika virus-specific monoclonal antibodies. The novel epitopes identified in this study shall be essential in designing multi-epitope vaccines capable of inducing antibody response against Zika virus infection.

Methods

ABCpred, BepiPred 2.0 and Kolaskar-Tongaonkar methods were used for predicting the linear B-cell epitopes, and Discotope 2.0 and ElliPro were used for the prediction of conformational epitopes. Linear epitopes were further checked for protective antigenicity, allergenicity and toxicity. Based on the stringent study design criteria, only the novel epitopes were considered for molecular docking with complementary determining regions of potent Zika virus-specific monoclonal antibodies.

Results

Nineteen linear and five conformational epitopes were shortlisted based on protective potential, non-allergic and non-toxic properties for Zika virus E protein, from which nine linear and three conformational epitopes were identified as novel. Molecular docking studies revealed that the novel linear epitopes, one each from EDIII, EDII, EDI and EDI/DIII hinge were involved in epitope-CDR interactions with potent neutralizing Zika virus E-specific mouse monoclonal antibody ZV-67. Moreover, the novel EDII epitope was exclusively engaged in epitope-CDR interactions of potent neutralizing Zika virus E-specific human monoclonal antibody Z3L1. None of the linear epitopes of Zika virus NS1 were ascertained as novel based on our study criteria. Conformational epitopes were identified as novel for NS1 protein.

Conclusion

This study identified Zika virus-specific novel epitopes of envelope and non-structural -1 proteins in the currently co-circulating Indian strains. Furthermore, in-silico validation through molecular docking added insight into antigen-antibody interactions, paving way for future in vitro and in vivo studies.
Community-based models for neglected tropical diseases affecting the skin: a scoping review
Authors: Hotopf India , Chowdhury Shahreen , Robert Guillermo , Sellers Mary Ellen , Phillip Maneesh , Fastenau Anil , del Mar Marais Maria , Vettel Constanze , Rahman Mijanur , Singh Rajni Kant , Hill Becks , Bekere Ahmed , Dean Laura
Published: February 2025

Skin neglected tropical diseases (NTDs) cause physical impairments, and socioeconomic and mental health impacts, often exacerbated by social stigma. The WHO 2030 road map calls for integrated, person-centred care; community-based groups (CBGs) present a community-led solution. However, evidence is limited and CBGs are not consistently being operationalised across health systems. The UPLIFT study is developing and piloting a harmonised CBG tool. This scoping review aimed to identify preferred practices in existing skin-NTD CBG models and recommend a holistic framework for best practice. We searched four peer-reviewed databases and key organisations’ websites, for terms related to CBGs and skin-NTDs. Eligible studies explored community models and skin NTDs and were published in English from 2000 onwards. Studies with quantitative, qualitative, or mixed method approaches, and secondary analysis or evidence synthesis were eligible. Studies failing to fulfil the criteria, opinion pieces, cross-sectional surveys, editorials, and case studies were excluded. Outcomes on key CBG domains were thematically identified and explored from literature and discussions with subject matter experts: self-care, mental health, livelihood, and governance. Data were compiled in Excel and charted according to CBG domain and other key information (e.g., outcome and method of measurement), before writing up findings thematically. Fifty-four eligible citations were identified, including 38 peer-reviewed papers. Most studies were pretest/posttests conducted in Asia, targeting mainly leprosy, with heterogeneity in study designs and evaluative measures. Only four studies explored all CBG domains, with few CBGs including formal mental health support, livelihood activities and advocacy and awareness activities. Current research on the burden of skin-NTDs is predominantly focused on leprosy, leaving a significant gap in research on other skin-NTDs, particularly in the African region. Most CBGs are failing to integrate into health systems and mainstream important programmatic components such as sustainability and gender considerations. To address these gaps and work towards a harmonised CBG approach, we present a framework of best practice and recommend further research, targeting multiple skin-NTDs in unison.
Assessment of laser ablation and solution-based ICP-MS applications commonly used in otolith geochemical analysis of marine teleosts
Authors: Zapp Sluis Michelle , Lippi Daniel L. , Sanchez Phillip J. , Miller Nathaniel R. , Stephens Shane A. , Ferreira Beatrice P. , Rooker Jay R.
Published: February 2025

Different applications of inductively coupled plasma mass spectrometry (ICP-MS) have the potential to influence results of otolith geochemical assays. Laser ablation and solution-based ICP-MS were compared on paired otoliths from three species of juvenile fish representative of estuarine (red drum [Sciaenops ocellatus]), coastal/reef (gray parrotfish [Sparisoma axillare]), and pelagic (blackfin tuna [Thunnus atlanticus]) ecosystems. Additionally, two laser ablation techniques (continuous line transects and series of spots) were performed to determine whether these two commonly used approaches yielded comparable results. No significant differences existed between line transects and spots for any of the three species investigated, with high correlations occurring for all otolith element:Ca (E:Ca) values retained for statistical testing (Mg:Ca, Mn:Ca, Sr:Ca, Ba:Ca), suggesting that both laser ablation techniques produced equivalent otolith E:Ca values. In contrast, pronounced differences in E:Ca values were detected between laser ablation (across otolith transverse section) and solution-based (whole otolith dilution) applications on paired sagittal otoliths. While some E:Ca discrepancies varied among the three species, overall otolith E:Ca values were higher when quantified by laser ablation, except for Ba:Ca which tended to be higher when analyzed by solution-based ICP-MS. Differences observed between laser ablation and solution-based applications are the result of the allometric growth of the otolith and may become more pronounced in older, larger individuals as the differential growth along the otolith axes becomes less uniform with age. Further, laser ablation techniques can examine life history profiles and discern fluctuations over time, proving a preferred application over solution-based analysis.
Effects of stiffener area in composite steel-concrete beam with web opening: numerical, experimental and theoretical investigation
Authors: Mastan Sheik , Sekar Anandh , S. Sindhu Nachiar
Published: February 2025

Generally, the Openings in composite steel-concrete beams (CBs) for conduits and pipelines often compromise their flexural capacity. To mitigate this, longitudinal stiffeners (LS) and transverse stiffeners (TS) are strategically placed near the web openings. While previous research has explored various opening shapes and stiffener placements, limited studies have examined the impact of stiffener area on flexural performance. This study investigates the influence of stiffener area on the bending performance of composite beams with openings (CBOs). Numerical analysis using ABAQUS (v6.14) was conducted on beams with circular (CBC), rectangular (CBR), and triangular (CBT) openings, varying the breadth of stiffener (b) of LS and TS as 4 mm, 6 mm, 8 mm, and 10 mm. Results indicate that the ultimate load-carrying capacity of CBC with LS and TS increased from 290.50 kN (without stiffeners) to 375.56 kN, 383.46 kN, 387.42 kN, and 400.00 kN as the stiffener breadths were increased to 4 mm, 6 mm, 8 mm, and 10 mm, respectively, finally achieving a 37.6% improvement and comparable to 401.70 kN capacity of a beam without openings (CB). For CBR and CBT with the maximum breath of stiffener, the load-carrying capacities were 37% (380.50 kN) and 73% (336.86 kN) greater, respectively, compared to CBR and CBT without stiffeners. Thus, numerical results indicate that with an increase in the area of both stiffeners, the beam with openings exhibits an ultimate bearing capacity comparable to a beam without web openings. Further experimental investigation was performed on three specimens scaled down at a ratio of 1:0.32; here, the load-bearing capacity of the CBC with both stiffeners of the breath of 10 mm is 156.40 kN, which is 44% greater than the scaled-down CBC of 108.80 kN and comparable to the scaled-down CB’s capacity of 151.12 kN. These experimental and numerical results emphasise that combining LS and TS with the maximum area of stiffeners, i.e., l × b (b = 10 mm), is most effective in maintaining the stability and load capacity of CBOs. Finally, the numerical and experimental results are validated against the theoretical results.
Molecular mechanism of crisaborole combined with erythromycin against methicillin-resistant Staphylococcus aureus in vivo and in vitro
Authors: Zou Yinuo , Yu Lei , Xue Jinjing , Fang Tianqi , Sun Liping , Wang Jianfeng , Cui Minhe , Zhang Peng , Zhou Yonglin
Published: February 2025

The widespread presence of methicillin-resistant Staphylococcus aureus (MRSA) severely threatens convenient therapeutic options in the postantibiotic era. The use of combinations of existing drugs at this stage may be a viable strategy for dealing with complex drug-resistant MRSA infections. An checkerboard MIC (Minimum Inhibitory Concentration) assay, growth curve assay, bactericidal test and scanning electron microscope (SEM) assays were performed to determine whether crisaborole (AN2728), a PDE4 inhibitor for treating atopic dermatitis (AD), produced bactericidal effect with different antibiotics. Here, we identified (AN2728) produced a significant synergistic bactericidal effect with erythromycin, cefuroxime and rifampicin against different bacterial strains of Staphylococcus aureus (S. aureus), especially MRSA (FIC < 0.5) (p < 0.05). Transcriptome analysis, bacterial biofilm assay and several kit assays revealed that AN2728 could also simultaneously affect the membrane and transporter capacity of MRSA. Moreover, in a mouse skin infection model of MRSA, the combination of AN2728 and erythromycin showed remarkable treatment benefits, as shown by significantly reduced bacterial loading (p < 0.05), pathological lesions of the skin and an obvious anti-inflammatory effect (p < 0.05). To our knowledge, this study is the first to establish that AN2728 can cooperate with antibiotics such as erythromycin to completely kill MRSA and that AN2728 can be used to extend the usage life of different antibiotics to address the inevitability of severe MRSA infection.
The skin microbiome on healthy and inflammatory altered canine skin determined by next generation sequencing
Authors: Štempelová Lucia , Micenková Lenka , Andrla Petr , Strompfová Viola
Published: February 2025

Introduction

Human and animal skin is colonized by a complex microbial population. An imbalance of these microorganisms is often associated with dermatological diseases.

Methods

The aim of this work was to describe the skin bacterial microbiota composition of healthy dogs and dogs with inflammatory skin lesions. Genomic DNA was sequenced using primers that target the V4 region of the bacterial 16S rRNA gene. Superficial skin swabs were collected from eight body areas of six healthy dogs (n = 48) and directly from inflammatory altered canine skin (n = 16).

Results

The skin of healthy dogs was predominantly colonized by phylum Bacillota (34.4 ± 27.2%), followed by Actinomycetota (32.2 ± 20.3%), Pseudomonadota (16.4 ± 12.2%), and Bacteroidota (8.7 ± 11.6%). At the level of genera, Streptococcus spp. (19.4 ± 26.1%) was the most abundant genus across all samples collected from healthy skin, followed by Curtobacterium (5.4 ± 12.1%), Bacteroides (5.2 ± 11.1%) and Corynebacterium_1 (4.3 ± 13.2%). More specifically, Streptococcus spp. was the most abundant on the chin (49.0 ± 35.5%), nose (37.9 ± 32.1%), perianal region (21.1 ± 28.2%), abdomen (11.0 ± 12.8%), dorsal back (12.4 ± 10.3%) and interdigital area (5.5 ± 2.2%). Curtobacterium spp. was predominant on inner pinna (17.8 ± 24.8%) and axilla (6.7 ± 10.8%). Alpha diversity analysis (Shannon index) showed maximum on interdigital area but minimum on a chin (p-value: 0.0416). Beta diversity analysis showed clustering across samples from the individual skin sites but also across samples collected from individual dogs. Staphylococcus spp. was the most abundant genus in 12/16 samples collected from inflammatory skin. In addition, a lower bacterial diversity was observed in samples from skin lesions compared to samples from healthy canine skin.

Discussion

The results confirm the fact that the microbiome of healthy skin is very diverse. Compared to other studies, streptococci predominated on healthy canine skin. Shannon index showed only minor differences in diversity between different parts of canine skin. Results of beta-diversity showed the fact that the main force driving the skin microbiota composition is the individual, followed by the skin site. On the area of skin lesions, dysbiosis was observed with a significant predominance of staphylococci.
Recent insights and advances in gut microbiota's influence on host antiviral immunity
Authors: Liu Ying , Yan Danying , Chen Ran , Zhang Yingying , Wang Chuwen , Qian Guoqing
Published: February 2025

A diverse array of microbial organisms colonizes the human body, collectively known as symbiotic microbial communities. Among the various pathogen infections that hosts encounter, viral infections represent one of the most significant public health challenges worldwide. The gut microbiota is considered an important biological barrier against viral infections and may serve as a promising target for adjuvant antiviral therapy. However, the potential impact of symbiotic microbiota on viral infection remains relatively understudied. In this review, we discuss the specific regulatory mechanisms of gut microbiota in antiviral immunity, highlighting recent advances in how gut microbiota regulate the host immune response, produce immune-related molecules, and enhance the host's defense against viruses. Finally, we also discuss the antiviral potential of oral probiotics.
Rhythmic auditory cues improve gait asymmetry during unobstructed walking in people with Parkinson’s disease but have no effect on obstacle avoidance - AsymmGait-Parkinson study
Authors: Cursiol Jônatas Augusto , dos Santos Paulo Cezar Rocha , Beretta Victor Spiandor , Orcioli-Silva Diego , Simieli Lucas , Schlenstedt Christian , Coelho Daniel Boari , Barbieri Fabio Augusto
Published: February 2025

Introduction

This study investigated the influence of rhythmic auditory cues (RAC) on gait asymmetry (GA) during unobstructed and obstacle avoidance walking in people with Parkinson’s disease (PD) and neurologically healthy individuals.

Methods

Thirteen individuals with PD (70.33 ± 6.02 years) and 13 healthy controls (CG) (70.77 ± 7.56 years) participated in this study. They performed a total of five trials during unobstructed walking and 10 trials during obstacle walking under each auditory cue condition (without and with RAC). For obstacle walking, five trials were performed with each limb as leading during obstacle avoidance. First, the volunteers performed the trials without RAC. The trial order, unobstructed or obstacle walking, was randomly defined, and the cues (controlled by a metronome) were personalized according to participants’ cadence. The symmetric index of gait parameters was analyzed using 2 × 2 factorial analysis of variance (group and RAC as factors) separately for each gait type (unobstructed and obstructed walking).

Results

A group-by-auditory cue interaction for step velocity (p = 0.027) showed that the PD group exhibited 57.6% reduced asymmetry with RAC during unobstructed walking, with no significant effects observed for the CG. However, RAC had no effect on GA during obstacle avoidance walking in people with PD. Conversely, the CG exhibited 10.5% greater step length asymmetry, 7.1% greater step duration asymmetry, 7.0% greater step velocity asymmetry, and 10.6% greater double support duration asymmetry during obstacle avoidance with RAC (p < 0.001).

Conclusion

We conclude that RAC can reduce GA in people with PD during unobstructed walking, but appear to have no effect and negative effects on GA during obstacle walking in people with PD and neurologically healthy individuals, respectively.
Relevance of persistent perfusion deficits on clinical outcomes after successful endovascular treatment: a prospective serial magnetic resonance study
Authors: Valls Carbó Adrián , Palomar Alicia , Laredo Carlos , Werner Mariano , Dorado Laura , Remollo Sebastià , Munuera Josep , Puig Josep , Silva Yolanda , Pérez de la Ossa Natalia , Gomis Meritxell , Bustamante Alejandro , Castaño Carlos , Muñoz Lucía , Domenech Sira , Terceño Mikel , Millán Mònica , Hernández-Pérez María
Published: February 2025

Background

Half of the patients who undergo successful recanalization after endovascular treatment (EVT) experience poor clinical outcomes. Impaired microvascular reperfusion (IMR) may explain this lack of improvement, but its frequency and clinical significance remain unclear. The study aims to describe the frequency and associated factors of IMR.

Materials and methods

We conducted a study on a cohort of patients with anterior large artery occlusion, treated with EVT at a single center, who achieved mTICI ≥2C. Perfusion MRI was obtained at arrival, up to 2 h after EVT (post-EVT MRI), and on day 5. IMR was observed only on the post-EVT relative cerebral blood volume (rCBV) maps as voxels within the follow-up ischemic lesion, exhibiting a > 15% asymmetry compared to a mirror homolog, in the absence of internal carotid occlusion, hemorrhagic transformation, or arterial reocclusion. Patients with an IMR volume greater than 5 mL were defined as having significant IMR. IMR was analyzed as a binary variable (presence/absence using the 5 mL cut-off) and by total and relative volume.

Results

IMR was present in 8 out of 33 patients (24.2%), with 4 out of 11 (36.4%) having mTICI 2C, and 4 out of 22 (18.2%) having mTICI 3. After adjustment for relevant variables, absolute and relative IMR volumes were associated with higher National Institutes of Health Stroke Scale (NIHSS) scores at 5 days (adjusted beta =0.50 [0.05, 0.96], p = 0.03) and at 24 h (adjusted beta = 0.11 [0.02, 0.19], p = 0.01). No independent associations were found between IMR and the 90-day modified Rankin Scale (mRS).

Conclusion

IMR is present in one-quarter of patients and is associated with worse early neurological outcomes.
A new nomogram for predicting 90-day outcomes of intravenous thrombolysis in patients with acute ischaemic stroke
Authors: Zhao Yingjie , Zhang Rui , Li Pan , Zhang Zhen , Yu Huan , Su Zhaoya , Xia Yandong , Meng Aiguo
Published: February 2025

Background

The aim of this study was to construct and validate a new nomogram to predict the risk of poor outcome in patients with acute ischemic stroke (AIS) after intravenous thrombolytic therapy (IVT).

Methods

A total of 425 patients who received IVT within 4.5 h of stroke onset were included in a retrospective study. All the patients were divided into training (70%, n = 298) and validation cohorts (30%, n = 127). Poor outcome (defined as a 90-day modified Rankin Scale score 3–5) was the primary outcome. Logistic regression was used for analysis of independent risk factors for poor outcome in patients with AIS. Nomograms of poor outcome in AIS patients were constructed using R software. Discrimination and calibration of the models were assessed using area under the receiver operating characteristic (ROC) curve (AUC) and calibration plots.

Results

Multifactorial logistic regression analysis showed that SII (OR = 1.001, 95% CI: 1.000–1.002, p = 0.008), SIRI (OR = 1.584, 95% CI: 1.122–2.236, p = 0.009), NIHSS (OR = 1.101, 95% CI: 1.044–1.160, p < 0.001), and history of diabetes mellitus (OR = 2.582, 95% CI: 1.285–5.188, p = 0.008) were the independent risk factors for the occurrence of poor outcome in AIS patients. The poor outcome nomogram for AIS patients was constructed based on the above independent risk factors. The training and validation cohort AUCs of the nomogram were 0.854 (95% CI: 0.807–0.901) and 0.855 (95% CI: 0.783–0.927), respectively. The prediction models were well calibrated in both the training and validation cohorts. The net benefit of the nomograms was better when the threshold probability ranges were 4.28–66.4% and 4.01–67.8% for the training and validation cohorts, respectively.

Conclusion

New nomogram includes NIHSS, SII, SIRI and diabetes as variables with the potential to predict the risk of 90-day outcomes in patients with AIS following IVT.
Effect of natural and synthetic noise data augmentation on physical action classification by brain–computer interface and deep learning
Authors: Gordienko Yuri , Gordienko Nikita , Taran Vladyslav , Rojbi Anis , Telenyk Sergii , Stirenko Sergii
Published: February 2025

Analysis of electroencephalography (EEG) signals gathered by brain–computer interface (BCI) recently demonstrated that deep neural networks (DNNs) can be effectively used for investigation of time sequences for physical actions (PA) classification. In this study, the relatively simple DNN with fully connected network (FCN) components and convolutional neural network (CNN) components was considered to classify finger-palm-hand manipulations each from the grasp-and-lift (GAL) dataset. The main aim of this study was to imitate and investigate environmental influence by the proposed noise data augmentation (NDA) of two kinds: (i) natural NDA by inclusion of noise EEG data from neighboring regions by increasing the sampling size N and the different offset values for sample labeling and (ii) synthetic NDA by adding the generated Gaussian noise. The natural NDA by increasing N leads to the higher micro and macro area under the curve (AUC) for receiver operating curve values for the bigger N values than usage of synthetic NDA. The detrended fluctuation analysis (DFA) was applied to investigate the fluctuation properties and calculate the correspondent Hurst exponents H for the quantitative characterization of the fluctuation variability. H values for the low time window scales (< 2 s) are higher in comparison with ones for the bigger time window scales. For example, H more than 2–3 times higher for some PAs, i.e., it means that the shorter EEG fragments (< 2 s) demonstrate the scaling behavior of the higher complexity than the longer fragments. As far as these results were obtained by the relatively small DNN with the low resource requirements, this approach can be promising for porting such models to Edge Computing infrastructures on devices with the very limited computational resources.
Hypofractionated stereotactic radiotherapy using coplanar VMAT for single small brain metastasis: dosimetric analysis and clinical outcomes
Authors: Lai Jialu , Li An , Zeng Xianhu , Liu Jia , Zhou Lin
Published: February 2025

Purpose

To evaluate the dosimetric parameters and clinical outcomes of hypofractionated stereotactic radiotherapy (HSRT) for small brain metastases [BMs; planning target volume (PTV) ≤ 4 cm3) via coplanar volumetric modulated arc therapy (C-VMAT).

Methods

Between March 2019 and February 2023, 68 patients with a single BM treated with Linac-based HSRT (24–39 Gy in three fractions) via C-VMAT and a 3-mm PTV margin were enrolled in this retrospective analysis. A frameless head–neck–shoulder thermoplastic mask, whose immobilization accuracy is inferior to that of specialized mask fixation systems, was used to immobilize patients. Dosimetric parameters and clinical outcomes were evaluated.

Results

C-VMAT provided clinically satisfactory treatment plans, with median gradient index, conformity index, homogeneity index, and PTV coverage values of 4.30, 1.05, 1.28, and 98%, respectively. The median volumes of normal brain tissue receiving 18 Gy, 21 Gy, and 23 Gy were 7.29 cm3, 5.33 cm3, and 4.40 cm3, respectively. High delivery accuracy was observed, with a gamma passing rate ≥90% for all plans. As of June 2023, the median follow-up time was 9.1 months. The intracranial objective response rate and disease control rate were 64% and 96%, respectively. The median intracranial progression-free survival was 26.9 (95% CI, 12.7–41.1) months. The 1- and 2-year local control (LC) rates were 91.5% (95% CI, 80.1%–100%) and 83.2% (95% CI, 64.6%–100%), respectively. The 1- and 2-year intracranial control rates were 70.9% (95% CI, 55.2%–86.6%) and 51.2% (95% CI, 32.6%–69.8%), respectively. Only four irradiated lesions progressed at the end of follow-up. The cerebral radiation necrosis rate of all patients was 7.4%.

Conclusion

C-VMAT HSRT combined with a 3-mm PTV margin is an effective and safe treatment modality for small BMs.
XueBiJing injection reduced mortality in sepsis patients with diabetes
Authors: Liu Yan , Dai Hengheng , Li Yixuan , Yang Tianyi , Zhang Dandan , Hu Chaoyue , Liu Si , Feng Zhiqiao , Zhang Chi , Yang Xiaohui
Published: February 2025

Introduction

Sepsis patients with diabetes are at a high clinical risk. It is well reported that XueBiJing injection has good clinical benefit in sepsis individuals. However, there is no relevant report about the efficacy and safety of XBJ in sepsis patients with comorbid diabetes.

Methods

Data of two large randomized controlled clinical trials (XBJ-SAP (ChiCTR-TRC-13003534) and EXIT-SEP (NCT0323874)) were combined, and post hoc analyses were performed. Sepsis patients with diabetes were further divided into the XBJ-treated group and placebo group based on inclusion and exclusion criteria. The primary (28-day mortality) and secondary outcomes (mortality in the ICU and in the post-randomization hospital, acute physiology, and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score) were compared between the XBJ treatment and placebo groups in sepsis patients with the diabetes status at baseline. Moreover, the occurrence of adverse events (AEs) was also assessed.

Results

At the study baseline, a total of 378 sepsis patients (227 men [60.0%] and 151 women [40.0%]; mean [SD] age, 60.3 [11.1] years) were considered to have diabetes, of which 177 received XBJ and 201 received placebo administration. Among these sepsis patients with diabetes, the mortality at 28 days was significantly lower in the XBJ group than in the placebo group (29 of 173 patients [16.8%] vs. 56 of 198 patients [28.3%], P = 0.01), and the absolute risk difference was 11.5% (95% CI, 3.1%–19.9%). Furthermore, there was no difference in the overall incidence of adverse events (AEs) when XBJ was used (24.4% [42 of 172 patients] vs. 27.7% [54 of 195 patients].

Discussion

The present study underscores the pivotal role of XBJ in modulating the immune response among sepsis patients suffering from diabetes mellitus, exploring the positive effects of XBJ on sepsis patients with diabetes mellitus. The efficacy and safety of XBJ compared with those of the placebo were consistent with the overall trial findings, demonstrating that XBJ is efficacious in sepsis patients with diabetes and suggesting that there is no need for special safety precautions.

Trial Registration Identifier

ChiCTR-TRC-13003534 and NCT0323874.