bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifocal osteochondromatous proliferation and paraneoplastic hematologic dyscrasia in the context of latent Epstein-Barr virus reactivation: a case of oncologic and infectious pathophysiology
Authors: Khalil Zeyad Hossam Atta , Osman Taha Ali
Published: January 2025

This case report describes a 15-year-old male with multifocal osteochondromatous proliferation and paraneoplastic hematologic dyscrasia, linked to latent Epstein-Barr virus reactivation. Radiographic and advanced imaging revealed widespread skeletal lesions consistent with osteochondromatosis. Hematologic evaluation indicated pancytopenia with dysplastic megakaryocytes and marrow infiltration. Immunohistochemical staining confirmed latent Epstein-Barr virus infection, suggesting its role in the pathogenesis of both the osteochondromatous and hematologic abnormalities. This case highlights the correlation between Epstein-Barr virus reactivation, bone proliferation, and paraneoplastic hematologic processes, which we believe has not yet been reported in the literature, emphasizing the need for a comprehensive diagnostic approach.
Integrated care for multi-domain vulnerability during pregnancy: a retrospective cohort study
Authors: Munshi Sushma C. , Hoex Eline C. I. , Weggelaar-Jansen Anne Marie , Knijff Esther M. , van der Wilk Eline C. , Steegers Eric A. P. , Bijma Hilmar H.
Published: January 2025

Purpose

Psychosocial risk factors are frequently present in pregnant women and are associated with adverse maternal and neonatal outcomes. Professional guidelines recommend early detection of vulnerability and provision of multidisciplinary care, including an integrated care plan for pregnant women with social factors, such as residing in deprived areas, teenage pregnancy, and psychiatric illness. However, to date, such approach is impeded by lack of data on co-occurrence of vulnerability. Therefore, we aim to describe co-occurrence of psychiatric illness, social factors or substance use during pregnancy.

Methods

A retrospective cohort study of 1002 pregnant women referred for evaluation by a multidisciplinary team because of psychiatric illness, social factors or substance use in a university hospital in a large city in the Netherlands. Data from medical charts between January 2017 and May 2022 were extracted and analyzed by univariate and bivariate analysis.

Results

Multi-domain vulnerability was present in 83% of women and most frequently involved the following patterns: psychiatric illness with social factors and chronic physical illness (24%), psychiatric illness with social factors (14%), social factors with chronic physical illness (13%) and psychiatric illness with chronic physical illness (12%). Single-domain vulnerability was present in 17% of women, involving most frequently social factors (9%) and psychiatric illness (8%).

Conclusion

The majority of women with psychiatric illness, social factors or substance use have multi-domain vulnerability. There is a need for a novel approach to care to address vulnerability in pregnant women.
Advancements in gene therapies targeting mutant KRAS in cancers
Authors: Wang Yuhang , Bui Thuy Anh , Yang Xinpu , Hutvagner Gyorgy , Deng Wei
Published: January 2025

Mutations in the KRAS gene are well-known tumourigenic drivers of colorectal, pancreatic and lung cancers. Mechanistically, these mutations promote uncontrolled cell proliferation and alter the tumour microenvironment during early carcinoma stages. Given their critical carcinogenic functions, significant progress has been made in developing KRAS inhibitors for cancer treatment. However, clinical applications of these KRAS inhibitor compounds are limited to specific cancer types which carry the relevant KRAS mutations. Additionally, clinical findings have shown that these compounds can induce moderate to serious side effects. Therefore, new approaches have emerged focusing on the development of universal therapeutics capable of targeting a wider range of KRAS mutations, minimising toxicity and enhancing the therapeutic efficacy. This review aims to examine these therapeutic strategies in the context of cancer treatment. It firstly provides an overview of fundamental KRAS biology within the cell signalling landscape and how KRAS mutations are associated with cancer pathogenesis. Subsequently, it introduces the development of current KRAS inhibitors which target certain KRAS mutants in different types of cancer. It then explores the potential of gene therapy approaches, including siRNA, miRNA and CRISPR methodologies. Furthermore, it discusses the use of lipid-based nanocarriers to deliver gene cargos for targeting KRAS gene mutants. Finally, it provides the insights into the future prospects for combatting KRAS mutation-associated cancers.

Graphical Abstract
Inefficient incentives for energy saving in tenancy law and policy options to remedy the landlord-tenant dilemma
Authors: Reutter Leo
Published: January 2025

The rental building sector faces challenges due to the so-called landlord-tenant dilemma. This issue arises because landlords have no direct financial benefits from energy efficiency retrofits if the tenant pays the energy bill. On the other hand, tenants have little motivation to save energy if the landlord covers this cost. The primary landlord-tenant dilemma results from rent control limiting rent levels in existing tenancies. The secondary dilemma is due to the undervaluation of energy cost savings in the new rental market. Tenancy law, through the allocation system for energy and retrofit costs, can either address or worsen these issues. This paper develops an analytical model to examine how efficiently various allocation systems incentivize retrofits and energy conservation and how they compare in terms of improving the welfare of both landlords and tenants. I analyze several systems: a free market model without and with rent control, the current German system, a slight variation of the German system, the Swedish inclusive rent system, a consumption-based partially inclusive rent system, and a novel demand-based partially inclusive rent system. The German status quo could theoretically offer optimal incentives if it were ideally set up; however, it interacts in a complex way with other aspects of German tenancy law, hindering optimal design. In contrast, the demand-based partially inclusive rent system is more likely to set efficient incentives consistently but would require substantial reforms in tenancy law.
The hyperintensionality of art
Authors: Vacek Daniela , Vacek Martin
Published: January 2025

Daniel Nolan successfully predicted a hyperintensional revolution in metaphysics in his 2014 paper ‘Hyperintensional Metaphysicsʼ. He argued that hyperintensionality is not restricted to representations. However, it seems that one of the most promising candidates for non-representational hyperintensionality has not yet been considered as such: art. We will argue that art can provide a rather strong case for non-representational hyperintensionality. One reason for this is that the hyperintensionality of art cannot be captured via a representational kind of hyperintensionality.
The bright and dark side of blue-enriched light on sleep and activity in older adults
Authors: Barroggi Constantino Débora , Lederle Katharina A. , Middleton Benita , Revell Victoria L. , Sletten Tracey L. , Williams Peter , Skene Debra J. , van der Veen Daan R.
Published: January 2025

Low indoor light in urban housing can disrupt health and wellbeing, especially in older adults who experience reduced light sensitivity and sleep/circadian disruptions with natural aging. While controlled studies suggest that enhancing indoor lighting may alleviate the negative effects of reduced light sensitivity, evidence for this to be effective in the real world is lacking. This study investigates the effects of two light conditions on actigraphic rest-activity rhythms and subjective sleep in healthy older adults (≥ 60 years) living at home. Two photon-matched lights were compared; a control white light (4000 K) and a blue-enriched white light (17000 K) at two different intensities (300–450 lx and 1100–1200 lx respectively). Participants (n = 36, 25 female) completed an 11-week randomized, cross-over study, comprising 1 week of baseline, 3 weeks of self-administered light exposure (2 h in the morning and 2 h in the evening), and 2 weeks of washout for each light condition. Participants completed sleep diaries, wore a wrist actigraph and a light sensor necklace, and collected urine to measure 6-sulphatoxymelatonin. Longer duration of morning blue-enriched light significantly improved rest-activity rhythm stability and decreased sleep fragmentation. More time spent above 2500 lx increased actigraphy amplitude, daytime activity, and advanced bedtime. Evening light exposure, however, increased sleep latency and lowered sleep efficiency. Our findings show morning blue-enriched light is beneficial whereas evening light should be avoided. Optimal timing of self-administered light interventions thus may offer a promising strategy to improve sleep and rest-activity rhythms in older adults in real-world settings.
Robotic hiatus hernia surgery: learning curve and lessons learned
Authors: Garsot Elisenda , Company-Se Georgina , Clavell Arantxa , Viciano Marta , Herrero Christian , Nescolarde Lexa
Published: January 2025

New procedures like the robotic approach require proficiency to ensure patient safety and satisfactory functional results. Hiatal hernia surgery serves as a suitable training procedure for upper gastrointestinal tract surgeons transitioning to the robotic approach. This study aims to evaluate the outcomes of implementing the robotic approach in hiatal hernia surgery at a tertiary hospital and to assess the associated learning curve. A retrospective review was conducted on 54 patients (58 surgeries) between June 2019 and March 2024, including both primary and revision robotic antireflux surgeries. The study focused on perioperative outcomes, symptom resolution, and the surgical learning curve, assessed using Cumulative Sum analysis. The results showed that global surgical time averaged 124 ± 57 (54–350) min, 127 ± 38 (116–139) for Primary Surgery and 164 ± 84 (115–212) min for Revisional Surgery. There were no conversions to laparoscopic or open approach. The global median of hospital stay was 2 days (2 for Primary Surgery and 3 for Revisional Surgery) and three patients required readmission (2 for Primary Surgery and 1 for Revisional Surgery). Postoperative complications occurred in 3 patients. Symptom resolution was achieved in 90% of Primary Surgery group and 85.7% of Revisional Surgery group. Learning curve described three phases: 1-training (case 1 to 14), 2-plateau (15 to 25) and 3-expertise phase (25 onwards). The robotic approach in hiatal hernia surgery is feasible with minimal morbidity, short hospital stays, and excellent functional results. With previous experience in laparoscopic approach and esophagogastric surgery the learning curve can be reduced to 14 procedures.
Grocery Shopping Under Simplified Marginal Value Theorem Predictions
Authors: Schlender Tabea , Rieger Alex , Eggert Frank
Published: January 2025

This study examined whether supermarkets can be considered patches in the marginal value theorem (MVT) sense despite their particular features and whether they are models of human food foraging in resource-dense conditions. On the basis of the MVT, the quantitative relationship between gains in the Euro and patch residence time was modeled as an exponential growth function toward an upper asymptote, allowing the choice of an optimal strategy under diminishing returns. N = 61 participants were interviewed about their current shopping trip and contextual variables at a German supermarket and provided data to estimate relevant model parameters. A nonlinear model of the patch residence time and resulting gain based on an exponential function was fitted via nonlinear orthogonal distance regression. The results generally revealed the relationships predicted by the model, with some uncertainty regarding the estimation of the upper asymptote due to a lack of data from participants with long residence times. Despite this limitation, the data support the applicability of the MVT-based model. The results show that approaches from optimal foraging theory, such as the MVT, can be used successfully to model human shopping behavior even when participants’ verbal reports are used.
Sensorless Position Estimation in Electromagnetic Launchers Using Recurrent Neural Networks with Repeated k-Fold Cross-Validation
Authors: Özbay Harun , Özer İlyas , Dalcali Adem , Çetin Onursal , Temurtaş Feyzullah
Published: January 2025

Systems utilizing electromagnetic launchers transform energy from one state to another. In electromagnetic launchers, the launched object follows the magnetic field generated by one or more fixed coils to achieve motion. Knowing the position of the projectile within the coil is crucial for efficient launching. In traditional systems, the position of the projectile is detected using different sensors. In this study, a sensorless method is proposed using Recurrent Neural Networks (RNNs) to estimate the projectile’s position based on current and voltage signals. Various RNNs architectures, including SimpleRNN, Long Short-Term Memory (LSTM), Gated Recurrent Unit (GRU), and Bidirectional GRU (Bi-GRU), are evaluated through repeated k-fold cross-validation. The GRU model achieved the highest accuracy with 94.88%, demonstrating the feasibility of sensorless position estimation in electromagnetic launchers. However, limitations such as the sensitivity of the model to noise in electrical measurements and the need for extensive data for training must be addressed. Despite these challenges, the proposed method offers a cost-effective and simplified alternative to sensor-based systems, particularly in environments where sensor integration is impractical. This approach has the potential to enhance the reliability and performance of electromagnetic launch systems.
Chronic Urticaria in Africa, What We Know and What We Do Not: A Systematic Review
Authors: Day Cascia , Peter Jonny
Published: January 2025

Purpose of Review

Despite global incidence, considerable morbidity, and diverse triggers, CU is poorly characterized amongst diverse African populations. This systematic review aims to describe available African CU studies and unmet needs.

Recent Findings

Overall 221 publications were screened and 29 were eligible for full review. These publications represented only 12 of 54 African countries, with 38% from Nigeria. Most publications described CU within the context of dermatology out-patient clinics(21/29), with a CU prevalence of 0.03–10.4%. Two studies detailed CU demographics, with a female predominance and median age of 30–40 years. CU patients reported variable associations with infections, including T.canis(Egypt), and H.pylori(Nigeria and South Africa), with other risk factors including foods, food additives, and low vitamin D levels. UAS was reported for < 100 CU patients, and only two studies detailed and CU co-morbidities, while none addressed other patient-reported outcome or quality-of-life measures, treatment access and/or efficacy.

Despite considerable disease prevalence, CU is poorly detailed in African populations. Further CU studies are required to detail phenotypes, disease severity and describe treatment use and unmet needs.
Effect of artificial viscosity on shocked particle-laden flows for staggered grid Lagrangian methods
Authors: Barclay Paul L. , Harrison Alan K.
Published: January 2025

Shocked particle-laden flows are important to many natural and industrial processes. When simulating these systems, artificial viscosity is often required to prevent numerical artifacts, such as ringing, from arising in the pressure and density fields. The linear and quadratic coefficients of the artificial viscosity determine the amount of smoothing that occurs in these fields. For particle-laden flows, however, many of the fluid–particle interaction forces, for example, the pressure gradient force and unsteady forces, depend on gradients in the fluid fields. Furthermore, while the shock passes over a particle, these forces can be more dominant than drag. This means that the artificial viscosity coefficients affect how a particle and fluid interact when simulating shocked particle systems. Here this effect is investigated for isolated particles and for a particle curtain using a staggered grid Lagrangian approach. The artificial viscosity coefficients have a significant impact on the maximum force that a fluid imparts to a particle, which is important for determining whether a particle will break up in response to the shock. Furthermore, it is found that the density ratio between the particle and the fluid is important in determining whether the artificial viscosity coefficients have a significant impact on the particle’s motion.
Exponiertheit im Sportunterricht
Authors: Edelmann Tino , Müller Arno , Jurkowski Susanne
Published: January 2025

Im Sportunterricht sind Schüler:innen aufgrund der Öffentlichkeit unterrichtlicher Handlungen besonders exponiert. Die damit einhergehende mögliche soziale Bewertung durch Mitschüler:innen kann das emotionale Erleben des Sportunterrichts beeinflussen. Positive Sozialbeziehungen, die einen sicheren Rahmen für die Lernenden schaffen, erscheinen unverzichtbar. In der vorliegenden Studie wurde der Zusammenhang zwischen der Qualität der Sozialbeziehungen und dem emotionalen Erleben in exponierten Sportunterrichtsphasen untersucht. Es nahmen N = 82 Schüler:innen aus vier Klassen der Jahrgangsstufen fünf bis sieben an der Untersuchung teil (M = 11,65, SD = 0,91, 56,1 % weibl.). Über Selbsteinschätzungen der Schüler:innen wurden die Qualität der Lehrer:in-Schüler:innen-Beziehung und die Qualität der Peerbeziehungen erfasst. Exponiertheit wurde für insgesamt 36 einzelne Unterrichtsphasen aus zwölf Sportstunden anhand eines Kodiersystems auf der Grundlage von Beobachtungen beurteilt. Darüber hinaus berichteten die Schüler:innen für jede Unterrichtsphase über ihr emotionales Erleben (Zufriedenheit, Freude, Wut/Ärger). Mehrebenenanalysen zeigen, dass eine stärkere Exponiertheit mit weniger Zufriedenheit und Freude und mehr Wut/Ärger zusammenhängt. Günstige Sozialbeziehungen wirken sich hingegen positiv auf das emotionale Erleben aus. Eine positive Beziehung zur Lehrkraft moderiert zudem den Zusammenhang zwischen der Exponiertheit und dem emotionalen Erleben in dem Sinne, dass auch bei stärkerer Exponiertheit mehr Freude und weniger Wut/Ärger erlebt werden. Die Ergebnisse unterstreichen die Bedeutung von Beziehungsqualitäten im Sportunterricht und verweisen darauf, Überlegungen zur Exponiertheit in der Unterrichtsgestaltung zu berücksichtigen.
Effects of Intermittent Sprint-Based Heat Acclimation at Various Pedal Resistances on Physiological Responses During Incremental Exercise
Authors: McGregor Callum , Marley Andrew , Babraj John
Published: January 2025

Purpose

Standard heat acclimation (HA) protocols (low-moderate intensity over a continuous 7–14 days) restore performance and thermoregulation but lack specificity and practicality for intermittent sports athletes. This study compared different pedal resistances in a 3-week intermittent sprint-based HA protocol.

Methods

Fourteen physically active adults were assigned to a sprint pedal resistance training group (TG): 0.075 kg/kg (7.5TG, 6 males, 1 female) or 0.085 kg/kg (8.5TG, 5 males, 2 females). Participants completed baseline incremental time to exhaustion test (TTE), continued with own training for 3 weeks before post-control TTE, then carried out 6 × 15 s cycle sprints with 30 s recovery followed by 30 min low intensity cycling thrice weekly for 3 weeks before completing post-HA TTE test. Testing and HA were completed at 38 °C and 30% relative humidity.

Results

Both groups improved TTE from baseline to post-HA (7.5TG: 9.6% ± 10.8%, 8.5TG: 7.4% ± 3.1%) and post-control to post-HA (7.5TG: 11.0% ± 11.7%, 8.5TG: 6.7% ± 3.9%). Maximal power improved from baseline to post-HA (7.5TG: 293 ± 40 W vs. 321 ± 46 W, 8.5TG: 318 ± 90 W vs. 339 ± 96 W), while only 7.5TG improved maximal power from post-control to post-HA (289 ± 42 W vs. 321 ± 46 W). From baseline to post-HA and post-control to post-HA, only 7.5TG increased time till maximum skin temperature (460 ± 76 s vs. 509 ± 75 s, 461 ± 72 s vs. 509 ± 75 s, respectively) and minimum core-skin gradient (461 ± 71 s vs. 510 ± 74 s, 455 ± 75 s vs. 510 ± 74 s, respectively), while exercising core temperature remained unchanged in both groups. Both groups increased sweat rate (7.5TG: 7.0 ± 3.4 mg/cm2/min vs. 9.6 ± 4.1 mg/cm2/min, 8.5TG: 5.7 ± 3.6 mg/cm2/min vs. 8.3 ± 4.3 mg/cm2/min). Only 7.5TG delayed the onset of blood lactate accumulation from baseline to post-HA (259 ± 126 s vs. 354 ± 86 s).

Conclusion

Intermittent sprint-based HA improves TTE performance and sweat rate while a lighter sprint pedal resistance offers, greater thermal adaptation and fatigue tolerance.
Comparative efficacy of NIBS and Physical Exercise on cognitive function in patients with MCI or AD: a systematic review and meta-analysis
Authors: Jiang Yi , Guo Zhiwei , Zhou Xiaobo , He Jiayuan , Wang Yanyan , Jiang Ning
Published: January 2025

Non-invasive brain stimulation (NIBS) and physical exercise (PE) intervention are currently the main and promising non-pharmacologic therapies for Alzheimer’s Disease (AD) or Mild cognitive impairment (MCI), but it is not clear which one is the most effective. Therefore, the aim was to compare the effectiveness of NIBS and PE interventions on cognitive function in MCI/AD, which can further elucidate their advantages and disadvantages in cognitive efficacy and facilitate the optimization of treatment strategies based on the specific cognitive status of patients. Randomized controlled trials (RCTs) were searched from online databases until December 2023. Standardized Mean Changes pre- and post-treatment were calculated for cognitive outcomes measures. 79 RCTs met the inclusion criteria. For the global cognitive scale, PE significantly affected AD and MCI. Both NIBS and PE had a sustained and significant impact on AD/MCI based on the follow-up. In sub-category functions, NIBS had a significant effect on memory for both AD and MCI. However, PE only had a significant effect on AD, not on MCI. For executive function, only NIBS had a significant effect on AD. For language, NIBS and PE both had a significant impact only on AD. For attention, the only significant effect was NIBS on AD. NIBS significantly affects more cognitive domains of AD than PE, and significantly improves the memory function of MCI. Given the current evidence, NIBS appears to be a more promising intervention approach for delaying cognitive decline in patients with MCI or AD compared to PE.

Graphical Abstract
Developing a curriculum on antimicrobial stewardship for pediatric residents: a needs assessment
Authors: Sattler Matthew M. , Greer Sara , Lockowitz Christine R. , Newland Jason G. , Facer Evan E. , Wolfe Katie
Published: January 2025

Objective:

Identify essential components of a curriculum on antimicrobial stewardship (AS) for pediatric residents.

Design:

Survey.

Setting:

Academic tertiary care children’s hospital.

Participants:

Pediatric residents and infectious diseases (ID)/AS content experts (CE), including pediatric ID faculty, fellows, nurse practitioners, and pharmacists.

Methods:

Residents were surveyed to assess prior AS experiences and usefulness of education in different AS domains (e.g., antimicrobial resistance [AMR]). CE was surveyed to identify content to include in an AS curriculum. A specific topic (e.g., resistance in Staphylococcus aureus) achieved consensus if ≥80% of CE identified the topic as “very” or “extremely” important.

Results:

Thirty-three of 110 pediatric residents responded to the resident survey (response rate 30%). Spectrum of activity (97%), empiric therapy (94%), and duration of therapy (94%) were the domains identified by the most residents as “very” or “extremely” useful. All CE responded to the CE survey (n=26). Thirty-nine of 105 topics (37%) met the consensus threshold. The domains with most topics achieving consensus were empiric therapy (11/13 topics, 85%) and duration of therapy (5/8 topics, 63%). Only one topic was identified within the domains of antibiotic allergies, diagnostics, and AMR, reflecting 18%, 14%, and 6% of the potential topics within each domain, respectively.

Conclusions:

A pediatric AS curriculum focused on empiric therapy and duration of therapy is likely to meet the needs of both learners and CEs.
Antitrust and corporate taxation
Authors: Lee Jonghoon , Pond Amy
Published: January 2025

Although citizens value competitive markets and support small businesses, we observe substantial variation in market concentration. Why do politicians abstain from taking action to reduce concentration? We propose an often overlooked political benefit to concentrated markets: When concentration increases, competition is less pronounced and firms earn larger profits. These profits can be taxed for government revenue or used to reward business-friendly politicians. We expect politicians to impose more lenient competition policies toward firms that provide larger sources of revenue. Moreover, this relationship should be especially strong under authoritarian political institutions, where politicians only weakly value the free market and consumer outcomes and where institutional commitments to unbiased policies are weak. We derive our theoretical claims from a formal model. We draw on both cross-country evidence and evidence from Turkey at the firm and industry level to evaluate our claims. We find that as political institutions become less representative, firms that make higher tax payments tend to control more assets, operate in more concentrated industries, and engage in higher value M&As. Our study points to the weak provision of competition policies as a source of rent-seeking.
Governing intelligence: Singapore’s evolving AI governance framework
Authors: Allen Jason Grant , Loo Jane , Campoverde Jose Luis Luna
Published: January 2025

This paper provides an outline analysis of the evolving governance framework for artificial intelligence (AI) in Singapore. Across the Singapore government, AI solutions are being adopted in line with Singapore’s “Smart Nation Initiative” to leverage technology to make impactful changes across society and the economy. In tandem, Singaporean authorities have been assiduous to release a growing number of governance documents, which we analyse together to chart the city-state’s approach to AI governance in international comparison. The characteristics of Singapore’s AI governance approach include an emphasis on consensus-building between stakeholders (particularly government and industry but also citizens) and voluntary or “quasi” regulation, lately with an emphasis on promulgating standards (AI Standards, n.d.) and audit-like frameworks. Singaporean regulators have also been early movers (globally, and especially in the region) in the promulgation of normative instruments on AI governance including developing the world’s first AI Governance Testing Framework and Toolkit, AI Verify. The Singapore approach may be compelling for other jurisdictions in the region and around the world with an interest in a collaborative, balanced and consensual approach to governing AI outside of strict regulatory mechanisms. However, any jurisdiction adopting aspects of its evolving model would have to duly account for relevant differences in social and institutional conditions.
The effect of probiotics, prebiotics and synbiotics on gut microbial community profile in overweight and obese Latin American and Caribbean populations: a systematic review of human trials
Authors: Bineid Manahil M. , Liu Litai , Ventura Eduard F. , Bansal Sakshi , Curi-Quinto Katherine , del Valle-Mendoza Juana , Walton Gemma E. , Vimaleswaran Karani Santhanakrishnan
Published: January 2025

Oral supplementation with probiotics, prebiotics, and synbiotics is a novel potential complementary therapy for addressing overweight and obesity through gut microbiota modulation. This systematic review provides a comprehensive summary of the existing evidence to guide future research. Literature searches were conducted in four databases to identify human trials published until May 2024 that examined the impact of probiotic, prebiotic, or synbiotic interventions on faecal microbiota composition changes in overweight and obese participants from Latin American and Caribbean populations (LACPs). Of the 13,090 identified records, five randomised controlled trials (RCTs) from Brazil, Mexico, and Chile met the inclusion criteria for this review. The included RCTs evaluated different forms of therapies over short-term interventions (6 or 8 weeks), with sample sizes ranging from 21 to 39 participants across the studies. Variations in the reported outcomes were observed due to differences in supplement formulation, dosage, population characteristics, and methodological heterogeneity. The findings indicate that the available data are inadequate to establish definitive conclusions regarding the impact of biotic treatments on gut microbiota profiles in LACP. Further research with larger sample sizes and precise microbiota analysis is required to elucidate the implications of dietary interventions on gut microbiota in obesity and related disorders.
Relationship between bilingual experiences and social biases: the moderating role of motivation to respond without prejudice
Authors: Castro Sofía , Kałamała Patrycja , Bukowski Marcin , Wodniecka Zofia
Published: January 2025

Previous studies have reported fewer social biases in bilinguals compared to monolinguals. However, it is unclear whether the expression of social biases varies across the bilingualism spectrum. This article investigates the connections between different dimensions of bilingual experience and the expression of explicit bias. We analyzed the responses of 389 bilinguals to a battery of questionnaires on bilingual and multicultural experiences, explicit bias, internal and external motivation to respond without prejudice and executive control. The results show that more diverse language-use and language-learning experiences were associated with lower explicit bias among bilinguals who had lower internal motivation to respond without prejudice (i.e., motivation driven by personal values). This study presents novel evidence on the relationships between bilingual experiences and the expression of social biases.
Predicting vocabulary knowledge in adult L2 learners: The role of word-level variables across educational backgrounds
Authors: Vanbuel Marieke
Published: January 2025

This study examines how word characteristics like frequency, concreteness, part of speech and length predict Dutch vocabulary knowledge in 763 adult migrant L2 learners who vary widely in their educational levels in their L1, from minimal to extensive formal education. While the impact of these features on vocabulary learning is well-documented among tertiary-educated adult and adolescent L2 learners in the academic track of secondary education, its effect on low-educated adult L2 learners has hardly been explored. Findings confirm that word frequency, concreteness and length significantly predict receptive vocabulary knowledge, aligning with prior research. However, the study also reveals variations in the predictive power of word frequency and length among adults with different educational backgrounds. These results highlight the necessity to reassess the applicability of findings from current research on L2 receptive vocabulary, particularly concerning adult learners with reduced educational backgrounds.
Responsive judicial remedies
Authors: Dixon Rosalind , Yap Po Jen
Published: January 2025

Judicial remedies are the critical means by which courts worldwide enforce and implement constitutional rights. Yet constitutional remedies were largely overlooked by early political process theorists, such as John Hart Ely. Contemporary comparative political process theory (CPPT) or comparative representation-reinforcing theory (CRRT) pays much greater attention to remedial questions, including the use of a range of ‘weak’ judicial remedies. These CPPT/CRRT scholars have highlighted the risks as well as advantages associated with the use of such remedies, but they have not reached any consensus on how to strike this balance and optimise their use. The article therefore draws on one specific recent version of CPPT/CRRT, namely the theory of ‘responsive judicial review’, to propose one way to strike this balance, namely: In cases impacting the ‘democratic minimum core’, courts should generally prefer strong remedies, with delayed relief only applied for prudential reasons; for other cases, courts should deploy more dialogic remedies, but generally these delayed or suspended remedies should be accompanied by a judicial statement of pre-defined strong remedies that take effect automatically in the event of legislative inaction. In this way, this article suggests that courts can give weak remedies ‘bite’, and hence promote actual legislative debate and dialogue, rather than incentivise legislative inaction after their rulings.
Two Sites in East Asia Add to Spatiotemporal Heterogeneity of Wildfire Activity Across the Paleocene–Eocene Thermal Maximum
Authors: Chen Zuoling , Li Chenyan , Yang Shiling , Lü Peizong , Tang Zihua , Sun Jimin , Ni Xijun , Fang Linhao , Ding Zhongli
Published: January 2025

The Paleocene–Eocene Thermal Maximum (PETM; ∼56 Ma) was a period of extreme global warming associated with a massive influx of isotopically light carbon into the ocean–atmosphere system. The burning of Paleocene peatland (wildfire hypothesis) has been proposed as a potential light carbon source. In addition, numerical models have predicted that wildfire activity would intensify in response to CO2‐induced global warming. In this study, we tested the wildfire hypothesis and model prediction by tracing the wildfire history across the PETM in East Asia using polycyclic aromatic hydrocarbons (PAHs). The PAH record exhibited notable spatiotemporal heterogeneity, indicating that wildfire activity varied widely across different regions and time periods during the PETM and highlighting the complex interplay between climate, vegetation, and fire dynamics. Global wildfire records do not support the global burning of Paleocene peatland; therefore, a wildfire‐related light carbon source requires close scrutiny.
A Planetary Perturbation Like No Other
Authors: Micalizio Caryl-Sue
Published: January 2025

Scientists are tackling “the most profound questions about life itself” with complex computer modeling, billion-year-old bacteria, and old-fashioned fieldwork.
Dynamic hydrogen-bonding enables high-performance and mechanically robust organic solar cells processed with non-halogenated solvent
Authors: He Haozhe , Li Xiaojun , Zhang Jingyuan , Chen Zekun , Gong Yufei , Zhuo Hongmei , Wu Xiangxi , Li Yuechen , Wang Shijie , Bi Zhaozhao , Song Bohao , Zhou Kangkang , Liang Tongling , Ma Wei , Lu Guanghao , Ye Long , Meng Lei , Zhang Ben , Li Yaowen , Li Yongfang
Published: January 2025

Developing active-layer systems with both high performance and mechanical robustness is a crucial step towards achieving future commercialization of flexible and stretchable organic solar cells (OSCs). Herein, we design and synthesize a series of acceptors BTA-C6, BTA-E3, BTA-E6, and BTA-E9, featuring the side chains of hexyl, and 3, 6, and 9 carbon-chain with ethyl ester end groups respectively. Benefiting from suitable phase separation and vertical phase distribution, the PM6:BTA-E3-based OSCs processed by o-xylene exhibit lower energy loss and improved charge transport characteristic and achieve a power conversion efficiency of 19.92% (certified 19.57%), which stands as the highest recorded value in binary OSCs processed by green solvents. Moreover, due to the additional hydrogen-bonding provided by ethyl ester side chain, the PM6:BTA-E3-based active-layer systems achieve enhanced stretchability and thermal stability. Our work reveals the significance of dynamic hydrogen-bonding in improving the photovoltaic performance, mechanical robustness, and morphological stability of OSCs.
Lipidic folding pathway of α-Synuclein via a toxic oligomer
Authors: Sant Vrinda , Matthes Dirk , Mazal Hisham , Antonschmidt Leif , Wieser Franz , Movellan Kumar T. , Xue Kai , Nimerovsky Evgeny , Stampolaki Marianna , Nathan Magdeline , Riedel Dietmar , Becker Stefan , Sandoghdar Vahid , de Groot Bert L. , Griesinger Christian , Andreas Loren B.
Published: January 2025

Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized. We report an atomic-resolution structural characterization of a toxic pre-fibrillar aggregation intermediate (I1) on pathway to the formation of lipidic fibrils, which incorporate lipid molecules on protofilament surfaces during fibril growth on membranes. Super-resolution microscopy reveals a tetrameric state, providing insights into the early oligomeric assembly. Time resolved nuclear magnetic resonance (NMR) measurements uncover a structural reorganization essential for the transition of I1 to mature lipidic L2 fibrils. The reorganization involves the transformation of anti-parallel β-strands during the pre-fibrillar I1 state into a β-arc characteristic of amyloid fibrils. This structural reconfiguration occurs in a conserved structural kernel shared by a vast number of αS-fibril polymorphs including extracted fibrils from Parkinson’s and Lewy Body Dementia patients. Consistent with reports of anti-parallel β-strands being a defining feature of toxic αS pre-fibrillar intermediates, I1 impacts viability of neuroblasts and disrupts cell membranes, resulting in an increased calcium influx. Our results integrate the occurrence of anti-parallel β-strands as salient features of toxic oligomers with their significant role in the amyloid fibril assembly pathway. These structural insights have implications for the development of therapies and biomarkers.
RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses
Authors: Kabrani Eleni , Rahjouei Ali , Berruezo-Llacuna Maria , Ebeling Svenja , Saha Tannishtha , Altwasser Robert , Delgado-Benito Veronica , Pavri Rushad , Di Virgilio Michela
Published: January 2025

The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its DNA end protection activity during class switch recombination. In this study, we showed that RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into plasma cells upon immunization. Mechanistically, this phenotype is independent from RIF1’s role in DNA repair and class switch recombination, and reflects its ability to modulate the transcriptional status of a subset of BLIMP1 target genes. Therefore, here we show that, in addition to promoting antibody diversification, RIF1 fine-tunes the kinetics of late B cell differentiation, thus providing an additional layer of control in the establishment of humoral immunity.
Adaptive evolution of SARS-CoV-2 during a persistent infection for 521 days in an immunocompromised patient
Authors: Schmidt Hanno , Schick Lea , Podlech Jürgen , Renzaho Angélique , Lieb Bettina , Diederich Stefan , Hankeln Thomas , Plachter Bodo , Kriege Oliver
Published: January 2025

Immunocompromised patients struggle to adequately clear viral infections, offering the virus the opportunity to adapt to the immune system in the host. Here we present a case study of a patient undergoing allogeneic hematopoietic stem cell transplantation with a 521-day follow-up of a SARS-CoV-2 infection with the BF.7.21 variant. Virus samples from five time points were submitted to whole genome sequencing. Between the first detection of SARS-CoV-2 infection and its clearance, the patient’s virus population acquired 34 amino acid substitutions and 8 deletions in coding regions. With 11 amino acid substitutions in the receptor binding domain of the virus’ spike protein, substitutions were 15 times more abundant than expected for a random distribution in this highly functional region. Amongst them were the substitutions S:K417T, S:N440S, S:K444R, S:V445A, S:G446N, S:L452Q, S:N460K, and S:E484V at positions that are notorious for their resistance-mediating effects. The substitution patterns found indicate ongoing adaptive evolution.
Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington’s disease decades before clinical motor diagnosis
Authors: Scahill Rachael I. , Farag Mena , Murphy Michael J. , Hobbs Nicola Z. , Leocadi Michela , Langley Christelle , Knights Harry , Ciosi Marc , Fayer Kate , Nakajima Mitsuko , Thackeray Olivia , Gobom Johan , Rönnholm John , Weiner Sophia , Hassan Yara R. , Ponraj Nehaa K. P. , Estevez-Fraga Carlos , Parker Christopher S. , Malone Ian B. , Hyare Harpreet , Long Jeffrey D. , Heslegrave Amanda , Sampaio Cristina , Zhang Hui , Robbins Trevor W. , Zetterberg Henrik , Wild Edward J. , Rees Geraint , Rowe James B. , Sahakian Barbara J. , Monckton Darren G. , Langbehn Douglas R. , Tabrizi Sarah J.
Published: January 2025

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.5 years compared with 46 controls (false discovery rate (FDR) > 0.3). However, cerebrospinal fluid (CSF) markers showed very early signs of neurodegeneration in HDGE with elevated neurofilament light (NfL) protein, an indicator of neuroaxonal damage (FDR = 3.2 × 10−12), and reduced proenkephalin (PENK), a surrogate marker for the state of striatal medium spiny neurons (FDR = 2.6 × 10−3), accompanied by brain atrophy, predominantly in the caudate (FDR = 5.5 × 10−10) and putamen (FDR = 1.2 × 10−9). Longitudinal increase in somatic CAG repeat expansion ratio (SER) in blood was a significant predictor of subsequent caudate (FDR = 0.072) and putamen (FDR = 0.148) atrophy. Atypical loss of interruption HTT repeat structures, known to predict earlier age at clinical motor diagnosis, was associated with substantially faster caudate and putamen atrophy. We provide evidence in living humans that the influence of CAG length on HD neuropathology is mediated by somatic CAG repeat expansion. These critical mechanistic insights into the earliest neurodegenerative changes will inform the design of preventative clinical trials aimed at modulating somatic expansion. ClinicalTrials.gov registration: NCT06391619.
Database energy saving strategy using blockchain and Internet of Things
Authors: Yang Dexian , Yu Jiong , He Zhenzhen , Li Ping
Published: January 2025

This paper aims to construct a green environmental protection system by advancing database energy-saving techniques and optimizing the energy-saving mechanism against the backdrop of blockchain integration. The protocol classification of wireless sensor networks is examined within the context of the rapid growth of information technology. The analysis draws upon the database storage and sharing model and recent research examples that connect blockchain and database technology. Additionally, the paper investigates the blockchain data structure and storage path by analyzing the spatial–temporal correlation properties of blockchain data. The findings demonstrate that increasing the number of network nodes in the database system within a reasonable range can reduce the overall execution time. Additionally, as time progresses, the query traffic of the system database continues to increase. The research has practical implications in the domains of databases and the Internet of Things.
Mini-open transosseous repair with bursal augmentation improves outcomes in massive rotator cuff tears
Authors: El Safoury Yasser , Sabry Ahmed O.
Published: January 2025

Treatment of Massive rotator cuff tears (MRCT) is difficult, with high rates of retears. Using biological augmentation in the form of the highly vascular subacromial bursa, was used to improve tendon healing. This work aimed to evaluate the results of arthroscopic guided mini-open transosseous repair with bursal augmentation in the treatment of MRCTs in a five-step approach. Forty-eight patients, with a mean age of 63.15 years, were treated with this technique. The patients were evaluated with the constant, UCLA and VAS scores. Plain X-rays were performed to evaluate the CSA and MRI was done to confirm the diagnosis of MRCT and determine the degree of fatty degeneration. Ultrasound was done at 1 year post-operative to determine any retears. The mean follow-up period was 29 months ± 4.95. The Constant and UCLA mean scores improved from (52.52) to (89) and (13.2) to (30.5) respectively (p < 0.0001). The post-operative active flexion and abduction improved from a mean of (112° to 170°) and (136.2° to 167°) respectively, while ER improved from (62.8° to 70°) with their p values (p < 0.0001). Pain improved from a mean VAS of (5.85) to (0.5) (p < 0.0001). No deterioration of function was noted throughout the follow-up period, and no retears occurred on post-operative ultrasound evaluation. Mini-open transosseous repair with bursal augmentation in the treatment of MRCT is an effective and low-cost method that achieves satisfactory results with no retears.
Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells
Authors: Mohamed Hanan R. H. , Mohamed Basma A. , Hakeem George M. , Elnawasani Shahd H. , Nagy Maria , Essam Rawan , Diab Ayman , Safwat Gehan
Published: January 2025

Nanotherapy has emerged as a promising strategy for the targeted and efficient treatment of melanoma, the most aggressive and lethal form of skin cancer, with minimized systemic toxicity. However, the therapeutic efficacy of cobalt oxide nanoparticles (Co3O4NPs) in melanoma treatment remains unexplored. This study aimed to assess the therapeutic potential of Co3O4NPs in melanoma treatment by evaluating their impact on cell viability, genomic DNA and mitochondrial integrity, reactive oxygen species (ROS) generation and apoptosis induction in melanoma A-375 cells. Our findings demonstrated a concentration-dependent reduction in cell viability upon treatment with five Co3O4NP concentrations (0.2, 2, 20, 200, and 2000 µg/ml), with an IC50 value of 303.80 µg/ml. Treatment with this IC50 concentration significantly increased ROS generation, induced dramatic DNA damage, and disrupted mitochondrial membrane potential integrity. Flow cytometric analysis revealed apoptosis and necrosis induction following Co3O4NP exposure at the IC50 concentration value. Results of qRT-PCR analysis demonstrated remarkable dysregulation of apoptotic and mitochondrial genes, including a significant downregulation of apoptotic p53 and mitochondrial ND3 genes and marked upregulation of the anti-apoptotic gene Bcl2. These findings highlight the novel potential of Co3O4NPs as potent inducers of melanoma A-375 cell death in a concentration-dependent manner through excessive ROS production, genomic instability, mitochondrial dysfunction and dysregulation of apoptotic and mitochondrial gene expression, ultimately promoting apoptosis in A-375 cells. This study thus underscores the potential of Co3O4NPs as a promising nanotherapeutic candidate for melanoma treatment, warranting further exploration to elucidate their full biological and clinical applicability.