bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon alpha treatment of relapsing–remitting multiple sclerosis: long-term study of the correlations between clinical and magnetic resonance imaging results and effects on the immune function
Authors: Durelli L , Bongioanni MR , Cavallo R , Ferrero B , Ferri R , Verdun E , Bradac GB , Riva A , Geuna M , Bergamini L , Bergamasco B
Published: January 2025

Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) are proinflammatory cytokines which may be involved in the pathogenesis of MS. IFN-α counteracts many of the proinflammatory actions of IFN-γ and TNF-α. We treated 20 patients with relapsing-remitting (RR) MS with 9 MIU of recombinant IFN-α-2a (rIFN-α) (n =12) or placebo (n=8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions at serial MRI occurred in 2/12 rlFN-α-treated and in 7/8 placebo-treated patients (P<0.005). Only one new MRI lesion was detected in the rIFN-a group, while 27 new or enlarging lesions were detected in placebo group (P<0.0/J. Baseline lymphocyte IFN-γ (I9.I0±7.I2 U ml-1) and TNF-α (I8.05±5.34 pg ml-1) production significantly decreased to 3.03±0.66 (P<0.04) (for IFN-γ) and to 5.78±0.90 (P<0.04) (for TNF-α) after rIFN-α treatment. IFN-γ and TNF-α production was unchanged in the placebo group. rIFN-α was tolerated without drop-outs or serious side-effects, but fever, malaise, fatigue (interfering with daily activities in two patients) and leukopenia frequently occurred. High-dose chronic systemic rIFN-α might reduce clinical and MRI signs of disease activity in RRMS. The changes in cytokine production suggest that the effect is probably mediated by a down-regulation of proinflammatory cytokine.
Effect of interferon gamma on T lymphocytes from patients with multiple sclerosis
Authors: Grimaldi LME , Martino G
Published: January 2025

A central role in the complex immunology of MS is played by activated T lymphocytes. Proper antigenic stimulation, adequate major histocompatibility complex (MHC) coactivation and multiple cytokine signals regulate T-cell activation via the generation of intracellular calcium (Ca2+) transients necessary to up-regulate the genes controlling lymphocyte growth and differenbation. Interferon gamma (IFN-γ) exerts an autocrine/paracrine control of T-lymphocyte activity and is able to co-mediate most demyelinating events occurring in MS patients. The mechanisms by which IFN-γ exerts its effects include increased expression of MHC class II molecules on the surface of glial cells and stimulation of macrophage/microglial cell production of molecules toxic to myelin. Most intracellular events regulating these processes in lymphocytes are, however, still unknown. We have reported that in the majority of MS patients T lymphocytes (mainly CD4+) exposed to IFN-γ show a Ca2+ influx whose ion permeability and pharmacological properties differ from those of all Ca2+ influxes so far described. This IFN-γ-activated Ca2+ influx, which is probably sustained by a cationic channel, was observed in the majority of patients with MS, but only in a limited number of subjects affected by other neurological, active immune-mediated diseases or healthy control subjects. Moreover, the presence of the influx correlates with clinical and radiological evidence of disease activity and induces T-lymphocyte proliferation even when cells are suboptimally stimulated by activatory stimuli. We conclude that this new IFN-y-activated Ca2+ influx seems to be highly specific for MS (especially during its active phase), and could be important for the intracellular regulation of cells involved in demyelination. The presence of the influx in T lymphocytes from MS patients could account for the reported temporal association between infections and clinical relapses.
A “drop in the ocean”? Emerging adults’ experiences and understanding of targeted political advertising on social media
Authors: Hirsch Melanie , Binder Alice , Matthes Jörg
Published: January 2025

Political microtargeting practices aim at exposing social media users to political content that aligns with their preferences and interests. Hence, such exposure becomes a personal experience, dependent on individual perceptions. So far, research has rarely investigated young social media users’ personal experiences with targeted political advertising (TPA). In the present study, five qualitative focus group interviews with 20 young social media users ( Mage = 19.30, SD = 1.59) were conducted to descriptively explore young social media users’ experiences with TPA. The insights indicated little intuitive reflection about TPA and targeting disclosures on social media. Participants often based their knowledge on algorithms for commercial advertising. This awareness did not seem to translate to TPA automatically. Once aware of TPA, however, they intuitively understood its potential threats. Our insights highlight the importance of educational programs to increase adolescents’ and young adults’ TPA-related awareness.
Exploring a low sense of social belonging in first-generation students in post-pandemic university in Austria
Authors: Resch Katharina , Bleicher Ulrike
Published: January 2025

The study explores the social belonging of first-generation students in a large university in Austria after the pandemic. While social belonging is a complex notion and nebulous to define, this study applies n enhanced concept of student engagement, which views student engagement as active involvement and social belonging on behalf of a student, and as integration and social support measures on behalf of the university. A strong sense of social belonging is on the one hand fundamental to becoming a student and the likelihood to graduate, however, the institution must also provide social support and academic integration on the other hand. This study explores the social belonging of seven first-generation students in Austrian higher education applying a qualitative approach using narrative interviews. The findings illustrate that first-generation students navigate higher education under significant economic constraints and experience intermittent access to social support measures. They hold strong feelings of social belonging with friends outside the university and do not make new friends at university easily. The study shows that first-generation-students depend on financial and social support by their families more than others and that negative sentiments during studying block their active involvement in class, and thus their sense of belonging.
Provider Confidence in LSL Strategies With the d/Deaf+ Population
Authors: Richlin Blair , Blaiser Kristina M. , Bargen Gabriel Anne , Gallup Jenn
Published: January 2025

Although existing literature demonstrates the efficacy of cochlear implants for the d/Deaf+ (DHH+) population as well as use of listening & spoken language (LSL) strategies, there is a degree of provider discomfort working with the population. This study investigates confidence in the use of LSL strategies by providers working with children who are DHH+ and investigates levels of provider confidence applying LSL skills/knowledge with this same population. Despite responses from highly qualified and experienced providers, results indicate evidence that disparities in strategy utilization and provider confidence exist with the DHH+ population. Although providers report benefits and utilization of strategies there is a paucity of available research in applying LSL strategies with children who are DHH+. To better support providers, there is a need to operationally define the DHH+ population including how additional diagnoses impact language learning as well as understand how skills are categorized by developmental levels of language acquisition.
Open Distal Venous Arterialization Technique as an Opportunity for Patients With Critical Limb Ischemia: A Latin American Experience
Authors: Randial-Pérez Leonardo Jose , Portilla-Rojas Esteban , Pinzón-Pinto Mariana , Suárez-Gómez Santiago Andrés , Amorocho-Suárez Mateo , Contreras Carla , Cabrera-Vargas Luis Felipe
Published: January 2025

Background

Chronic limb-threatening ischemia (CLTI) leads to decreased quality of life and increased disease burden, resulting in progressive patient deterioration, limb amputation, and mortality.

Objectives

This study aims to present the outcomes of a Latin American experience using the open distal venous arterialization (DVA) technique for no-option limb salvage in a high volume CLTI center.

Methods

A retrospective case series study was performed including patients from 2018 to 2022 using a population from Bogotá, Colombia. Patients with no-option chronic limb-threatening ischemia underwent open DVA with a 12 month follow-up period. Variables such as operative time, hospital and ICU length of stay, graft material, re-interventions, 1-year patency, amputations and 1-year mortality were recorded.

Results

5 patients with a mean age of 71 years were intervened. 60% were male and 80% had a diabetes mellitus diagnosis. Four patients underwent a reverse great saphenous vein graft procedure and 1 composite polytetrafluoroethylene graft. A total of 80% of patients demonstrated graft patency after 1 year. No perioperative mortalities were recorded but one late postoperative mortality due to myocardial infarction occurred. One major amputation was required, minor amputations were performed in 2 of the patients.

Conclusion

Open DVA is a feasible low cost technique for adequately selected patients with favorable saphenous vein, as evidenced by the limb salvage and graft patency outcomes.
The Feasibility of Occupation-Based Coaching for Autistic Children and Primary Caregivers
Authors: Tkach Melanie Morriss , Dunn Winnie , Wolf Timothy J.
Published: January 2025

Autistic children participate less and have fewer opportunities to develop participation skills than nonautistic peers. The extent to which occupation-based coaching (OBC), a metacognitive strategy training intervention, affects participation in school-age autistic children is unknown. We conducted a single-group pretest-posttest design to evaluate the feasibility and preliminary effect of telehealth OBC for autistic children ( n = 13) and primary caregivers ( n = 12). Participants completed eight telehealth OBC sessions to address activity-based goals; they completed child, caregiver, and family outcomes pre- and post-intervention. Recruitment, retention, caregiver measure completion, and intervention adherence rates exceeded feasibility benchmarks. OBC had large effects on child performance (Hedge’s g = 1.65) and satisfaction (Hedge’s g = 1.89), a moderate effect on child sleep disturbance (Hedge’s g = 0.60), and small effects on child participation (Hedge’s g = 0.23) and family quality of life (Hedge’s g = 0.26). Further research in a large-scale study is warranted with changes to better support child measure completion and enhance the study protocol.
Precision medicine using molecular-target drugs in psoriatic arthritis
Authors: Miyagawa Ippei , Tanaka Yoshiya
Published: January 2025

Psoriatic arthritis (PsA) presents various clinical manifestations, including skin lesions, peripheral arthritis, axial involvement, enthesitis, nail involvement, dactylitis, and uveitis. In addition, it causes a high incidence of lifestyle-related diseases and an increase in cerebrovascular and cardiovascular events. As the pathology of PsA has been clarified, molecular-targeted drugs targeting tumor necrosis factor-α, interleukin (IL)-17A, IL-17A/F, IL-17 receptor, IL-12/23(p40), IL-23p19, Cytotoxic T-lymphocyte Antigen-4 (CTLA-4), Janus kinase, and phosphodiesterase-4 have been developed and are widely used in clinical practice. PsA is clinically and molecularly heterogeneous, and it is necessary to improve various clinical symptoms with limited treatment options simultaneously; therefore, rheumatologists sometimes encounter difficult situations in clinical practice. Hence, the development of precision medicine may improve treatment outcomes. Recently, the strategic use of molecular-targeted drugs based on the stratification of patients with PsA by peripheral blood lymphocyte phenotyping and serum cytokine concentrations has been reported to possibly lead to a higher therapeutic response. A randomized controlled trial was initiated to verify the efficacy of this treatment strategy. However, to make precision medicine in PsA feasible, shifting from conventional clinical trials to clinical trials based on biomarker profiles and accumulating further data are necessary.
Beyond de Patient: A Lesson in Vigilance and Care
Authors: Peschard-Franco Mariana
Published: January 2025

A neurology resident reflects on a pivotal moment during the assessment of an elderly patient, when attention shifts unexpectedly to the patient’s caregiver, his wife. The resident quickly recognizes a neurological deficit that could potentially be treated. Sensing the urgency, the resident rushes her to the emergency department, where immediate treatment enables the caregiver to regain her ability to continue caring for her husband. This experience teaches the resident a profound lesson about the importance of vigilance not only toward primary patients but also toward those quietly supporting them. It highlights how timely intervention can preserve the connections that bind families, emphasizing the role of healthcare providers in maintaining these bonds.
Single-center experience of venetoclax combined with azacitidine in young patients with newly diagnosed acute myeloid leukemia
Authors: Xu Xuezhu , Liu Rui , Chen Hongli , Yang Ruoyu , Gao Gongzhizi , He Aili , Wang Fangxia
Published: January 2025

Background:

Medical resources, especially blood products, were in short supply during the COVID-19. Less intensive therapy with hypomethylating agents/venetoclax (VEN) seems an effective treatment option for patients with acute myeloid leukemia (AML).

Objectives:

To retrospectively analyze the efficacy and safety of VEN combined with azacitidine (AZA) in young adult patients with newly diagnosed (ND) AML.

Design:

This was a retrospective study.

Methods:

The clinical data of 25 AML patients treated with the VEN + AZA regimen from January 2021 to December 2023 at our center were collected, compared with a randomized historical study cohort that was administered intensive chemotherapy (IC) from January 2018 to December 2019.

Results:

No rate of complete remission/complete remission with incomplete count recovery differences observed between the two arms reached statistical significance. Compared to traditional IC, minimal residual disease (MRD)-negative remission was achieved more quickly in patients treated with VEN + AZA regimens (after cycle 1: 8% in the IC group vs 56% in the VEN group, p = 0.0004; after cycle 2: 16% in the IC group vs 72% in the VEN group, p = 0.0001), especially in those AML patients who had a poor prognosis. The dependency of transfusion of red blood cell (RBC) and platelets during induction treatment was significantly lower in the VEN + AZA group (RBC: p = 0.0269; platelet: p = 0.0054). Compared with the standard IC, the incidence rate of non-hematological adverse events in VEN + AZA group was significantly decreased (infection: 100% vs 20%, p = 0.0001; gastrointestinal side effects: 48% vs 12%, p = 0.0055). The total hospitalization cost of the VEN group was significantly less than that of the IC group ( p = 0.0395).

Conclusion:

In conclusion, our study indicated that VEN + AZA with a higher MRD-negative remission rate and less toxic appeared to be a therapy option for young patients with ND AML. However, further well-designed studies with larger numbers of patients are needed to confirm the benefits of VEN + AZA in this population.
Workplace Attitudes  and Work-life Challenges-based Side-hustling Intentions of the Tech Professionals: A PLS-SEM-Based Approach
Authors: Seema Seema , Sachdeva Geeta , Mor Kiran , Mittal Amit
Published: January 2025

Alternative work arrangements especially side-hustling grew as a huge disrupting force in shaping the post-pandemic workplaces. The present study entails the empirical investigation of withdrawal cognitions of employees by quantifying the impact of job attitudes, particularly their workplace attitudes (WPAs) and work-life challenges (WLCs) on the moonlighting intentions (MLIs) of the tech professionals. As per the best knowledge of the authors, this is the earliest attempt to study both the WPAs and WLCs of tech professionals towards their MLIs through the lens of the attitudes and alternatives model of withdrawal cognitions. The study tests eight hypotheses to fulfil its objectives. Organisational commitment, turnover intentions, financial strain, entrepreneurial motivation and job strain are found to be positively and significantly impacting the MLIs of the workforce. Through this study, it is advised to both the organisational leadership and the Indian government to watch out for the long-run impacts before prohibiting moonlighting for their workforce and propose robust regulations on a national level in light of the evolution of hybrid workplaces. Research limitations, theoretical and practical implications along with future directions have also been revealed.
Supporting Self-Advocacy in Nutritional Health: Using Health Imaginaries to Navigate Student Wellness and University Resources
Authors: Kelly Jacquelyn , Gielstra Dianna , Oberding Tomáš J , Bruno Jim , Jordan Chris
Published: January 2025

This IRB-exempt, exploratory, mixed-methods study aims to show how integrating social representations of people, places, and things known as imaginaries can enhance a nutrition course for non-traditional adult learners early in academic programs to support their success. Using an Elicit, Design, Create, Deploy, and Research (EDCDR) process, the accommodations-eligible health imaginaries were embedded into resources and activities in the nutrition course to achieve universal design goals. Through an exploratory mixed methods approach, we evaluated the impact of these health and wellness-focused imaginaries on improving learners’ self-awareness and advocacy following curriculum adjustments. Pre-test and post-test course surveys of the intervention led to a small positive shift in scores, indicating increased student awareness and confidence regarding accommodation eligibility, timing, success, and faculty fairness. The Mann–Whitney U test revealed significant difference in students’ awareness and knowledge of accommodations and ADA resources following the intervention. Key areas of improvement included understanding accommodation eligibility ( z = −11.51, p < .001, r = 0.10), the request process ( z = −17.83, p < .001, r = 0.15), timing of requests ( z = −16.39, p < .001, r = 0.14), perceptions of accommodation success ( z = −15.02, p < .001, r = 0.13), and faculty fairness ( z = −10.92, p < .001, r = 0.09), with small but meaningful effect sizes. Qualitative results showed participants found the health and wellness course engaging and relatable, especially due to the realistic, diverse characters and their connection to real-life challenges in nutrition and health, though some noted issues with course-material alignment and imaginary character development. The intervention led to small but significant improvements in students’ knowledge and perceptions of accommodations, demonstrating its effectiveness as a low cost, scalable solution for supporting students in higher education.
Methods to account for shallow site effects in hybrid broadband ground-motion simulations
Authors: Kuncar Felipe , Bradley Brendon A , de la Torre Christopher A , Rodriguez-Marek Adrian , Zhu Chuanbin , Lee Robin L
Published: January 2025

Shallow site effects are indirectly considered in conventional hybrid broadband ground-motion simulations, and their proper incorporation may be key to improving ground-motion predictions at soil sites. This article presents and examines five methods to adjust hybrid simulations to account for these effects. These methods use different approaches to modeling site response and require different amounts of site-characterization data: Methods 1 and 2 use only proxy parameters (e.g. [Formula: see text], [Formula: see text]) to describe the site conditions, with Method 1 relying solely on proposed site response scaling factors in existing semi-empirical ground-motion models, and Method 2 incorporating a host-to-target velocity-profile adjustment; Methods 3 and 4 use a shear-wave velocity profile along with two different frequency-domain approaches to predict the linear site response, coupled with the nonlinear component of Method 1; and Method 5 uses 1D time-domain nonlinear site-response analysis and generally requires additional data to constrain nonlinear constitutive-model input parameters. The five methods are applied to four sites subjected to two levels of ground-motion intensity to illustrate the challenges involved in their implementation and to compare and contrast the resulting adjustments in terms of site amplification. The suitability and performance of each method will depend on multiple factors, including the availability of site-characterization data and complexity of the site, and hence, their relative advantages and disadvantages are discussed considering a broad range of scenarios.
Glucarpidase for Treatment of High-Dose Methotrexate Toxicity
Authors: Gupta Shruti , Kaunfer Sarah Allison , Chen Kevin L , Dias Julie-Alexia , Vijayan Anitha , Rajasekaran Arun , Prosek Jason , Truong Huong L. , Wood Anthony , Bassil Claude , Renaghan Amanda DeMauro , Shah Chintan V , Zhang Jingjing , Glezerman Ilya , Carlos Christopher , Kelly Katherine , Passero Christopher J , Drappatz Jan , Abudayyeh Ala , Shin Daniel , Sperati C. John , Yelvington Bradley J , Kanduri Swetha Rani , Neyra Javier A , Edmonston Daniel , Shirali Anushree C , Bansal Anip , Geara Abdallah , Mithani Zain , Ziolkowski Susan L , Rashidi Arash , Jakubowski Jonathan , Pujari Ashwini , Bond David A , Dotson Emily K , Wall Sarah A , Patton John T. , Barreto Jason N , Hermann Sandra M , Sheikh Mohammad Salman , Baz Rachid C , Lee Jae Hui , Lucchesi Nicholas , Kolman Michael , Rasheed Muhammad Ahsan , Afzal Afsheen , Kang Dasol , Mahesh Amrita , Hsu Raymond , Nicolaysen Anthony , Tefera Kibrewessen , Schretlen Claire , Miller Ryan M , Velez Juan Carlos Q , Flannery Alexander H , Aklilu Abinet M , Anand Shuchi , Chandrasekhara Soniya , Donley Vicki , Patel Ashka , Ni Jian , Krishnamurthy Shobana , Ali Rafia , Yilmam Osman A , Wells Sophia L , Ortega Jessica L , Green-Lingren Olivia L , Leaf Rebecca Karp , Sise Meghan E , Nayak Lakshmi , LaCasce Ann S. , Leung Nelson , Leaf David E
Published: January 2025

High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the U.S using a sequential target trial emulation framework. The primary end point was kidney recovery at hospital discharge, defined as survival to discharge with serum creatinine <1.5-fold baseline and without dialysis-dependence. Key secondary end points were time-to-kidney recovery, neutropenia and transaminitis on day 7, and time-to-death. Using multivariable logistic and Cox regression models, we compared outcomes in patients who received glucarpidase within 4 days following MTX initiation with those in patients who did not. Among 708 patients with MTX-AKI, 209 (29.5%) received glucarpidase. Overall, 183 (25.8%) had a primary end point event. Glucarpidase receipt was associated with a 2.70-fold higher adjusted odds of kidney recovery (95% CI, 1.69-4.31) compared to no glucarpidase receipt. Patients treated with glucarpidase also had faster time-to-kidney recovery (adjusted hazard ratio [aHR], 1.88, 95% CI, 1.18-3.33) and lower risks of grade ≥2 neutropenia (adjusted odds ratio [aOR], 0.50, 95% CI, 0.28-0.91) and grade ≥2 transaminitis (aOR, 0.50, 95% CI, 0.28-0.91) on day 7. There was no difference in time-to-death (aHR, 0.76; 95 CI, 0.49-1.18). These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI.
Age-dependent decline in sperm quality and function in a naturally short-lived vertebrate
Authors: Cattelan Silvia , Valenzano Dario Riccardo
Published: January 2025

Maximizing the life-long reproductive output would lead to the prediction that short-lived and fast aging species would undergo no – if any – reproductive senescence. Turquoise killifish (Nothobranchius furzeri) are naturally short-lived teleosts, and undergo extensive somatic aging, characterized by molecular, cellular, and organ dysfunction following the onset of sexual maturation. Here, we tested whether naturally short-lived and fast aging male turquoise killifish maximize reproduction and display minimal – if any, reproductive senescence. We analysed age-related changes in sperm traits, the proportion of fertilized eggs, as well as embryo survival. Contrary to the expectation of no reproductive aging, we found that turquoise killifish males undergo extensive reproductive aging, consisting in the age-dependent decline in sperm quality, decreased proportion of fertilized eggs and lower embryo survival. Our results indicate that male turquoise killifish do not trade-off age-dependent soma decline with life-long sustained reproductive fitness. Instead, somatic and reproductive aging appear to occur simultaneously. Our findings question generalized soma vs. reproductive senescence trade-off models and highlight the importance of integrating species-specific ecological and demographic constraints to explain observed life history traits.
Fusarium oxysporum assisted green synthesis of small-sized silver nanoparticles for high antibacterial, and photocatalytic decolorization performances
Authors: El-Sharkawy Reyad M. , Ahmed Inas A. , Kharboush Taghrid G.
Published: January 2025

Background

Novel platforms using nanotechnology-based medicines have exponentially increased in our daily lives. The unique characteristics of metal oxide and noble metals nanoparticles make them suitable for different fields including antimicrobial agents, cosmetics, textiles, wound dressings, and anticancer drug carriers.

Methods

This study focuses on the biosynthesis of small-sized SNPs using exo-metabolites of Fusarium oxysporum via bioprocess optimization using Plackett-Burman (PBD) and central composite designs (CCD) while evaluating their multifaceted bioactivities.

Results

The successful biofabrication of smaller-sized SNPs with an average particle size of ~ 5 nm was achieved upon the bioprocess optimization. The developed SNPs exhibited significant antibacterial activity against multidrug-resistant bacterial pathogens in a concentration- and time-dependent manner. The minimum inhibitory concentrations (MICs) for SNPs were 0.078 µg/ml (Escherichia coli), 0.156 µg/ml (Pseudomonas aeruginosa), and 1.25 µg/ml (Enterococcus faecalis), while the minimum bactericidal concentrations (MBCs) were correspondingly 0.156 µg/ml, 0.312 µg/l, and 1.25 µg/ml. SNPs-treated cells displayed bacteriostatic and bactericidal effects as revealed by time-kill assay and the ultrastructure changes observed in SEM and TEM analyses. The results marked the potent antioxidant activity of SNPs against DPPH, O2•−, H2O2, and OH-radicals with IC50 values of 74.3, 96.7, 116.6, and 167.9 µg/ml, respectively. Significantly, the biosynthesized SNPs displayed cytotoxic activity on MCF-7, A549, and HepG-2 cell lines with IC50 values of 89.4, 121.4, and 138.9 µg/ml, respectively. SNPs exhibited promising photocatalytic efficiency at different concentrations and times compared with dark conditions. The highest decolorization percentage of crystal violet dye was 98.60% after 240 min at 100 µg SNPs concentration.

Conclusions

The green synthesis of SNPs by F. oxysporum exometabolites is eco-friendly, and inexpensive, with the production of small-size, and greatly stabilized nanoparticles. This study corroborated that SNPs can be highly promising enough to be applied for antibacterial and anticancer control systems, for ameliorating free radical-related disorders, and as a photocatalyst for wastewater treatment.
Therapeutic extraction of second molars in orthodontics: a scoping review
Authors: Montasser Ziad M. , Montasser Mona A.
Published: January 2025

Objective

To review the literature to identify the present evidence on the extraction of second molars in orthodontics.

Materials & method

A search of the MEDLINE/PubMed®, Scopus, Web of Science™, and ProQuest® databases for full-text articles was done on March 5, 2024. The search went back till the 1st of January 1991 and was limited to articles in English. The results of the first search went through a preliminary check to remove duplicates and then the titles and abstracts of the articles were read to exclude the irrelevant studies, case studies, or reviews. The abstracts of the selected studies were read carefully to verify if the inclusion criteria were met. Finally, the full texts of the potentially eligible studies were read to apply the eligibility criteria and decide whether to include them in the review or not. The eligibility criteria were set following the PICO (population, intervention, comparison, and outcome) standard. The included studies were thoroughly summarized by extracting the most important information.

Results

The electronic search located a total of 103 articles distributed among the databases. Removing duplicates left 48 Studies. After careful assessment of the titles and abstracts, 32 studies were excluded leaving 16 studies. Applying the inclusion/exclusion criteria resulted in the exclusion of 2 studies and including 14 studies in the scoping review.

Conclusions

There is quite low level of evidence to support second molar extraction in orthodontics. Conducting a systematic review would not add much to the evidence as well-conducted RCTs are needed first.
Promising new drugs and therapeutic approaches for treatment of ovarian cancer—targeting the hallmarks of cancer
Authors: Hillmann Julia , Maass Nicolai , Bauerschlag Dirk O. , Flörkemeier Inken
Published: January 2025

Ovarian cancer remains the most lethal gynecological malignancy. Despite the approval of promising targeted therapy such as bevacizumab and PARP inhibitors, 5-year survival has not improved significantly. Thus, there is an urgent need for new therapeutics. New advancements in therapeutic strategies target the pivotal hallmarks of cancer. This review is giving an updated overview of innovative and upcoming therapies for the treatment of ovarian cancer that focuses specific on the hallmarks of cancer. The hallmarks of cancer constitute a broad concept to reenact complexity of malignancies and furthermore identify possible targets for new treatment strategies. For this purpose, we analyzed approvals and current clinical phase III studies (registered at ClinicalTrials.gov (National Library of Medicine, National Institutes of Health; U.S. Department of Health and Human Services, 2024)) for new drugs on the basis of their mechanisms of action and identified new target approaches. A broad spectrum of new promising drugs is currently under investigation in clinical phase III studies targeting mainly the hallmarks “self-sufficiency in growth signals,” “genomic instability,” and “angiogenesis.” The benefit of immune checkpoint inhibitors in ovarian cancer has been demonstrated for the first time. Besides, targeting the tumor microenvironment is of growing interest. Replicative immortality, energy metabolism, tumor promoting inflammation, and the microbiome of ovarian cancer are still barely targeted by drugs. Nevertheless, precision medicine, which focuses on specific disease characteristics, is becoming increasingly important in cancer treatment.

Graphical Abstract
Single cell and spatial analysis of immune-hot and immune-cold tumours identifies fibroblast subtypes associated with distinct immunological niches and positive immunotherapy response
Authors: Jenkins Benjamin H. , Tracy Ian , Rodrigues Maria Fernanda S. D. , Smith Melanie J. L. , Martinez Begoña R. , Edmond Mark , Mahadevan Sangeetha , Rao Anjali , Zong Hailing , Liu Kai , Aggarwal Abhishek , Li Li , Diehl Lauri , King Emma V. , Bates Jamie G. , Hanley Christopher J. , Thomas Gareth J.
Published: January 2025

Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like). IL-11 + iCAF were spatially associated with inflammatory monocytes and regulated in vitro through synergistic activation of canonical NF-κB signalling by IL-1β and TNF-α. FRC-like were enriched in immune-hot HPV+ve tumours, associated with CD4 + T-cells and B-cells in tertiary lymphoid structures and regulated through non-canonical NF-κB signalling via lymphotoxin. Pan-cancer analysis revealed several ‘iCAF’ subgroups present in both normal and cancer tissues; IL11 + iCAF were found in cancers from the gastrointestinal (GI) tract and transcriptomically distinct from iCAFs previously described in pancreatic and breast cancers with greater inflammatory properties; FRC-like fibroblasts were present at low frequencies in all tumour types, and were associated with significantly better survival in patients receiving checkpoint immunotherapy. This work clarifies and expands current literature on immunomodulatory CAFs, highlighting links with important immunological niches.
Transforming dementia research into practice: a multiple case study of academic research utilization strategies in Dutch Alzheimer Centres
Authors: Zhu Eden Meng , Buljac-Samardžić Martina , Ahaus Kees , Huijsman Robbert
Published: January 2025

Background

Non-pharmacological dementia research products, such as social and behavioural interventions, are generated in traditional university settings. These often experience challenges to impact practices that they were developed for. The Netherlands established five specialized academic health science centres, referred to as Alzheimer Centres, to structurally coordinate and facilitate the utilization of dementia research knowledge. This study leverages implementation science to systematically explore the research utilization strategies used by academic researchers from each Alzheimer Centre, on the basis of the “knowledge-to-action” (KTA) framework that includes knowledge creation, adaptation, dissemination and implementation.

Methods

Individual semi-structured qualitative interviews were conducted with 29 respondents across the five Alzheimer Centres in the Netherlands. Participants were selected through purposive (snowball) sampling. Interviews were conducted in-person and virtually through Microsoft Teams, and all were audio-recorded and transcribed verbatim. Data analysis was guided by the dimensions of the KTA framework.

Result

There was a high variation in the strategies used across the five Alzheimer Centres to bring non-pharmacological dementia research into practice. Selected strategies in each Centre were influenced by the typology of research products produced and the Centres’ organizational heritage. The knowledge creation and adaptation phases were mainly facilitated by funders’ guidance towards research impact and research product co-creation with patients and implementing organizations. Dissemination and implementation phases were often facilitated through utilizing support from university-based technology transfer offices to facilitate implementation and valorization and establishing and strategically leveraging formal infrastructure, such as public–private partnerships and professional collaborative networks.

Conclusions

Successful research utilization requires evolving researcher competencies to meet environmental demands and facilitating co-creation with research end-users and implementing partners. Understanding external determinants influencing research utilization in the Dutch dementia research ecosystem is crucial for capacity-building and aligning cross-sector agendas. The KTA framework appears to reveal the intricacies of research utilization, guiding future studies to explore strategies employed across various contexts.
Optimizing transcutaneous spinal stimulation: excitability of evoked spinal reflexes is dependent on electrode montage
Authors: Thatcher Kelly Lynn , Nielsen Karen Emily , Sandler Evan Blake , Daliet Oliver John , Iddings Jennifer Ann , Field-Fote Edelle Carmen
Published: January 2025

Background

There is growing interest in use of transcutaneous spinal stimulation (TSS) for people with neurologic conditions both to augment volitional control (by facilitating motoneuron excitability), and to decrease spasticity (by activating inhibitory networks). Various electrode montages are used during TSS, with little understanding of how electrode position influences spinal circuit activation. We sought to identify the thoracolumbar electrode montage associated with the most robust activation of spinal circuits by comparing posterior root-muscle reflexes (PRM reflexes) elicited by 6 montages. Additionally, we assessed tolerability of the stimulation during PRM reflex testing.

Methods

Fifteen adults with intact neurological systems participated in this randomized crossover study. PRM reflexes were evoked transcutaneously using electrode montages with dorsal–ventral (DV) or dorsal-midline (DM) current flow. DV montages included: [1] cathode over T11/T12, anodes over iliac crests (DV-I), [2] cathode over T11/T12, anodes over umbilicus (DV-U), [3] dual paraspinal cathodes at T11/12, anodes over iliac crests (DV-PI), and [4] dual paraspinal cathodes at T11/12, anodes over umbilicus (DV-PU). DM montages included: [5] cathode over T11/12, anode 5 cm caudal (DM-C), and [6] cathode over T11/12, anode 5 cm rostral (DM-R). PRM reflex recruitment curves were obtained in the soleus muscle of both lower extremities.

Results

Lower reflex thresholds (mA) for dominant (D) and nondominant (ND) soleus muscles were elicited in DV-U (D: 46.7[33.9, 59.4], ND: 45.4[32.5, 58.2]) and DV-I (D: 48.1[35.3, 60.8], ND: 45.4[32.5, 58.2]) montages compared to DV-PU (D: 64.3[51.4, 77.1], ND:61.7[48.8, 74.6]), DV-PI (D:64.9[52.1, 77.7], ND:61.4[48.5, 75.5]), DM-C(D:60.0[46.9, 73.1], ND:63.6[50.8, 76.5]), and DM-R(D:63.1[50.3, 76.0], ND:62.6[49.8, 75.5]). DV-U and DV-I montages demonstrated larger recruitment curve area than other montages. There were no differences in response amplitude at 120% of RT(1.2xRT) or tolerability among montages.

Conclusions

Differences in spinal circuit recruitment are reflected in the response amplitude of the PRM reflexes. DV-I and DV-U montages were associated with lower reflex thresholds, indicating that motor responses can be evoked with lower stimulation intensity. DV-I and DV-U montages therefore have the potential for lower and more tolerable interventional stimulation intensities. Our findings optimize electrode placement for interventional TSS and PRM reflex assessments.

Clinical Trial Number: NCT04243044.
Benefits of targeted deployment of physician-led interprofessional pre-hospital teams on the care of critically Ill and injured patients: a systematic review and meta-analysis
Authors: Lavery Matthew D. , Aulakh Arshbir , Christian Michael D.
Published: January 2025

Introduction

Over the past three decades, more advanced pre-hospital systems have increasingly integrated physicians into targeted roles, forming interprofessional teams. These teams focus on providing early senior decision-making and advanced interventions while also ensuring rapid transport to hospitals based on individual patient needs. This paper aims to evaluate the benefits of an inter-professional care model compared to a model where care is delivered solely by paramedics.

Methodology

A meta-analysis and systematic review were conducted using the guidelines of PRISMA 2020. Articles were identified through a systematic search of three databases and snowballing references. A systematic review was conducted of articles that met the inclusion criteria, and a suitable subset was included in a meta-analysis. The survival and mortality outcomes from the studies were then pooled using the statistical software Review Manager (RevMan) Version 8.2.0.

Results

Two thousand two hundred ninety-six articles were found from the online databases and 86 from other sources. However, only 23 articles met the inclusion criteria of our study. A pooled analysis of the outcomes reported in these studies indicated that the mortality risk was significantly reduced in patients who received pre-hospital care from interprofessional teams led by physicians compared with those who received care from paramedics alone (AOR 0.80; 95% CI [0.68, 0.91] p = 0.001). The survival rate of critically ill or injured patients who received pre-hospital care from interprofessional teams led by physicians was increased compared to those who received care from paramedics alone (AOR 1.49; 95% CI [1.31, 1.69] P < 0.00001).

Conclusions

The results of our analysis indicate that the targeted deployment of interprofessional teams led by physicians in the pre-hospital care of critically ill or injured patients improves patient outcomes.
Benchmarking Alzheimer’s disease prediction: personalised risk assessment using polygenic risk scores across various methodologies and genome-wide studies
Authors: Bellou Eftychia , Kim Woori , Leonenko Ganna , Tao Feifei , Simmonds Emily , Wu Ying , Mattsson-Carlgren Niklas , Hansson Oskar , Nagle Michael W. , Escott-Price Valentina ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

Background

The success of selecting high risk or early-stage Alzheimer’s disease individuals for the delivery of clinical trials depends on the design and the appropriate recruitment of participants. Polygenic risk scores (PRS) show potential for identifying individuals at risk for Alzheimer’s disease (AD). Our study comprehensively examines AD PRS utility using various methods and models.

Methods

We compared the PRS prediction accuracy in ADNI (N = 568) and BioFINDER (N = 766) cohorts using five disease risk modelling approaches, three PRS derivation methods, two AD genome-wide association study (GWAS) statistics and two sets of SNPs: the whole genome and microglia-selective regions only.

Results

The best prediction accuracy was achieved when modelling genetic risk by using two predictors: APOE and remaining PRS (AUC = 0.72–0.76). Microglial PRS showed comparable accuracy to the whole genome (AUC = 0.71–0.74). The individuals’ risk scores differed substantially, with the largest discrepancies (up to 70%) attributable to the GWAS statistics used.

Conclusions

Our work benchmarks the best PRS derivation and modelling strategies for AD genetic prediction.
Applications of Babalola q-convolution operator on subclass of analytic functions
Authors: Shaba Timilehin Gideon , Gunasekar Saravanan , Saliu Afis , Tchier Fairouz , Sudharsanan Baskaran
Published: January 2025

In this study, we present a specific type of analytic functions called $\mathfrak{B}_{\gamma}(q)$

B
γ

(
q
)
, characterized by the Babalola q-convolution operator. We examine the characteristics of this category and set the limits for the initial four coefficients. In addition, we establish the limits for the Toeplitz determinants of second and third order for the functions within this category. Our discoveries offer fresh perspectives on the behavior of these functions and aid in comprehending their structural characteristics.
No-tillage practice enhances soil total carbon content in a sandy Cyperus esculentus L. field
Authors: Wang Cong , Hu Yuxiang , Wu Hui , Wang Zhirui , Cai Jiangping , Liu Heyong , Ren Wei , Yang Ning , Wang Zhengwen , Jiang Yong , Li Hui
Published: January 2025

Background

No-tillage (NT) is a widely used field management to reduce soil erosion and degradation and is suggested to be beneficial for enhancing soil carbon (C) sequestration capacity. Nonetheless, the effects of NT on soil total carbon (TC) content in aeolian sandy soils are not extensively explored, and the underlying mechanisms are not clear. In our field experiments, the influence of NT and conventional tillage (CT) on sandy soil was studied.

Methods

We estimated the changes in soil TC in response to NT practice in a Cyperus esculentus L. field located at semi-arid Horqin sandy land, China. To unravel the underlying mechanisms, plant traits, soil properties and soil microbial characteristics were measured in parallel. The variations in soil bacterial community structure were investigated by 16S rRNA amplicon sequencing. The functionality of soil bacterial community was predicted based on OTU tables by using PICRUSt2.

Results

NT increased soil TC content in this sandy agroecosystem within a short-term experimental period, compared to CT. The underlying mechanisms might rely on three aspects. First, NT increased soil TC content through increasing photosynthesis and plant biomass, and thus, the plant-derived dissolved organic C. Second, NT increased the C immobilized in soil microbial biomass by increasing microbial C demands and C use efficiency. Third, NT increased the dominance of oligotrophic members in bacterial communities by decreasing available nutrient levels, which is associated with the recalcitrance and stability of the soil organic carbon.

Conclusions

The present study enriched our knowledge on the changes in the plant-soil-microbe continuum in response to NT in a semi-arid sandy agroecosystem. Still, this study provides a reference for modifying tillage practices to benefit crop yield as well as soil C sequestration.