bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transcriptional regulator Lrp activates the expression of genes involved in the biosynthesis of tilimycin and tilivalline enterotoxins in
Klebsiella oxytoca
Authors: De la Cruz Miguel A. , Valdez-Salazar Hilda A. , Rodríguez-Valverde Diana , Mejia-Ventura Santa , Robles-Leyva Nayely , Siqueiros-Cendón Tania , Rascón-Cruz Quintín , León-Montes Nancy , Soria-Bustos Jorge , Chimal-Cázares Fernando , Rosales-Reyes Roberto , Cedillo María L. , Yañez-Santos Jorge A. , Ibarra J. Antonio , Torres Javier , Girón Jorge A. , Fox James G. , Ares Miguel A. 
Published: December 2024

ABSTRACT

The toxigenic
Klebsiella oxytoca
strains secrete tilymicin and tilivalline enterotoxins, which cause antibiotic-associated hemorrhagic colitis. Both enterotoxins are non-ribosomal peptides synthesized by enzymes encoded in two divergent operons clustered in a pathogenicity island. The transcriptional regulator Lrp (

l

eucine-responsive

r

egulatory

p

rotein) controls the expression of several bacterial genes involved in virulence. In this work, we have uncovered novel findings that have significant implications. We determined the transcriptional expression of
aroX
and
npsA
, the first genes of each tilimycin (TM)/tilivalline (TV) biosynthetic operon in
K. oxytoca
MIT 09-7231 wild-type and its derivatives Δ
lrp
mutant and complemented strains. Our results suggest that Lrp directly activates the transcription of both
aroX
and
npsA
genes by binding to the intergenic regulatory region in a leucine-dependent manner. Furthermore, the lack of Lrp significantly diminished the cytotoxicity of
K. oxytoca
on HeLa cells due to reduced production of TM and TV. Altogether, our data present a new perspective on the role of Lrp as a regulator in cytotoxin-producing
K. oxytoca
strains and how it controls the expression of genes involved in the biosynthesis of their main virulence factors.

IMPORTANCE

Tilimycin (TM) and tilivalline (TV) are enterotoxins that are a hallmark for the cytotoxin-producing
Klebsiella oxytoca
strains, which cause antibiotic-associated hemorrhagic colitis. The biosynthesis of TM and TV is driven by enzymes encoded by the
aroX
- and NRPS-operons. In this study, we discovered that the transcriptional regulator Lrp plays a crucial role in activating the expression of the
aroX
- and NRPS-operons, thereby initiating TM and TV biosynthesis. Our results underscore a molecular mechanism by which TM and TV production by toxigenic
K. oxytoca
strains is regulated and shed further light on developing strategies to prevent the intestinal illness caused by this enteric pathogen.
ZnO/P3HT nanocomposite photoanodes for photoelectrochemical applications
Authors: Majumder Tanmoy , Mondal Suvra Prakash 
Published: December 2024

ZnO nanoparticle/poly(3-hexylthiophene) conducting polymer hybrid nanocomposite photoanode has been grown on FTO-coated glass substrates. ZnO nanoparticles (ZnO NPs) were synthesised using sol–gel methods. Structural and optical properties of ZnO NPs studied using AFM, TEM and UV–Vis spectroscopy. The size of the ZnO nanoparticles varies from 10[Formula: see text]nm to 45[Formula: see text]nm. The photoelectrochemical properties of the P3HT film, ZnO nanoparticles and ZnO/P3HT nanocomposite photoanodes have been studied under dark and illumination of white light. The ZnO/P3HT hybrid photoanode shows photosensing properties with a high on-off ratio (∼90) at 0[Formula: see text]V. Open circuit photovoltage (OCPV) response and OCPV delay of ZnO/P3HT nanocomposite has been studied. The stability of ZnO nanoparticle-poly(3-hexylthiophene) nanocomposite as a photoanode has been investigated using 1[Formula: see text]Hz chopped light pulse.
Procedural Content Generation - The Open Source Success Story of Wave Function Collapse
Authors: Lux Mathias 
Published: December 2024

With OpenAI's Dall-E, Midjourney, and Adobe Firefly, computer-generated visual content has hit the mass market. Machine learning-based algorithms can now create, and re-mix multimedia content based on huge corpora of images and videos and relieve creative professionals of tedious work. While this has gained much momentum lately, procedurally generated content (PCG) has been around for quite some time already. Especially in video game development, randomized levels, behavior, aesthetics, and even narratives increase replayability and engage the audience longer. Prominent examples are Minecraft and Diablo, where the game world is randomly generated, and Borderlands, where in-game items are generated on the fly. PCG is applied on multiple levels with different purposes, like generating terrain, weather, road and transport networks, house layouts, puzzles, textures, and mazes, just to name a few. Hedrikx et al. [1] give a comprehensive overview of the topic.
In a typical scenario, a mix of algorithms is employed to create content on the fly. Generative grammar algorithms are often employed for vegetation, fractal noise is used to generate terrain and clouds, and simulation is used to create road networks or to erode terrain further. Lately, deep learning-based approaches have become available. The most notable example is AI Dungeon [2], where users converse with GPT in a text adventure. However, large neural networks require significant computational power and are hard to explain and constrain, so procedural content generation tends to use less complex algorithms, where game designers can give hard constraints to influence the outcome.
Free Movement of Services and Non-EU Citizen Staff – a U-turn from the CJEU? Comments on Case C-540/22, SN, ECLI:EU:C:2024:530
Authors: Peers Steve 
Published: December 2024

Abstract
The CJEU has recently decided that non-EU employees of EU companies providing services in another Member State require residence permits to work there for more than 90 days. This case note explores the rationale and implications of the Court’s judgment.
Numerical computations on thermal performance of large-scale Ti-Mn-based metal hydride storage reactor via open source CFD software
Authors: Babou Allal , Kerboua Ziari Yasmina , Kerkoub Youcef 
Published: December 2024

Certain metals and metal alloys can absorb hydrogen through an exothermic chemical reaction, resulting in the formation of metal hydrides. To maintain a rapid charging rate, the produced heat must be extracted as rapidly as it is generated. This study was attempted to evaluate the heat transfer enhancement in a cylindrical hydrogen storage reactor equipped with a central tube for large-scale applications using a 3D transient model. Finite-volume simulations are carried out using the open-source software package OpenFOAM to systematically investigate the impacts of material thermophysical properties, cooling media, and heat exchanger design on the heat transfer behaviors and hydrogen storage rate. The reactor’s performance was evaluated in terms of temperature and total hydrogen mass history profiles, in addition to pressure drop. The findings indicated that the charging time was improved by roughly 86%, compared to the case without thermal enhancement to attain 90% hydrogen storage capacity. A diminished pressure drop was observed between the water-based Al2O3 nanofluid with 5 vol% concentration and pure water at lowered coolant flow velocities, hence enhancing pumping power efficiency. Moreover, the results demonstrated that the storage rate is markedly improved by enhancing the effective thermal conductivity of the hydride bed, increasing the heat exchange area, accelerating the coolant flow rate, and lowering its temperature. The outcomes highlighted the possibility of advancing the current metal hydride reactor for practical application.
Hand Osteoarthritis in Elderly Women with Primary Knee Osteoarthritis: Prevalence and Pattern in the Indian Population
Authors: Dhaon Pooja , Singh Astha , Singh Kushal , Tiwari Siddharth , Khan Haseeb 
Published: December 2024

Aim: The aim of this study was to estimate prevalence of hand osteoarthritis (HOA) and identify patterns in female patients with symptomatic primary knee osteoarthritis (KOA) presenting in a rheumatology outpatient department (OPD). Methods: A hospital-based cross-sectional study was done among 145 female patients with primary KOA, as per American College of Rheumatology (ACR) criteria, utilising the right knee as the index knee. The presence of Kellgren–Lawrence (K-L) grade ≥2 radiological changes in two of three groups of hand joints in dominant hand was used to identify hand arthritis (HOA). Symptomatic HOA (SHOA) was defined as existence of hand discomfort within preceding month. Hand disability was measured using the Health Assessment Questionnaire (HAQ); a mean score of >0.5 was deemed to be a significant disability. Global Hand Kellgren–Lawrence Score (KLTOT) was used to assess radiographic severity of HOA. Results: The prevalence of HOA was found in 96 (66%) patients, with a higher prevalence in patients above 60 years of age. At the individual joint level, 102 (71.7%) patients had DIP involvement, 96 (66.2%) had PIP involvement, 40 (27.5%) had metacarpophalangeal (MCP) involvement, and 57 (34.4%) had involvement in the base of the thumb. SHOA was found in 48 (33%) patients, and significant disability was noted in 38 (26.2%) patients. There was a significant positive correlation between global KLTOT and body mass index (BMI) ( P = .004) and between global KLTOT and HAQ ( P = .002). A significant difference was found between HOA and the radiographic severity of the KOA ( P = .003) in comparison to patients without HOA. Conclusion: HOA is common in elderly women, especially those with primary KOA.
NR1D1exon6::MAML2exon2 Fusion-Positive Sarcomas: Two Additional Cases of an Emerging Soft Tissue Tumor Entity
Authors: Kantak Anura , Rekhi Bharat , Barwad Adarsh , Rastogi Sameer 
Published: December 2024

NR1D1::MAML1/L2 fusion-positive sarcomas constitute an emerging subtype of undifferentiated sarcomas, histopathologically composed of epithelioid and spindle cells. We describe two NR1D1exon6::MAML2exon2 fusion-positive sarcomas occurring in the occipital region of a 53-year-old female patient and the left shoulder of a 25-year-old male patient. Histopathologically, the former tumor comprised spindle and polygonal-shaped/epithelioid cells, while the latter comprised epithelioid cells. Immunohistochemically, the cells of the first tumor were positive for keratin cocktail (AE1/AE3), EMA, and p40. The other tumor lacked any epithelial marker immunoexpression and showed SATB2 positivity. Both the tumors were SMARCB1 proficient. While the former tumor was initially diagnosed as a sarcomatoid carcinoma, the latter was diagnosed as an undifferentiated sarcoma. Both patients underwent surgical resection as the primary treatment. One patient received adjuvant radiotherapy, whereas the other received ifosfamide and doxorubicin-based therapy. However, both the patients developed progressive disease, with one developing lung metastasis during relapse. There was a suboptimal response to chemotherapy in both patients. This study highlights the clinicopathological features of two rare and emerging sarcomas. It further emphasizes the value of high-throughput molecular testing, such as next-generation sequencing in the undifferentiated epithelioid, and spindle-cell sarcomas to identify the prognostic subtypes and differentiate these neoplasms from their histopathological mimics.
Evaluation of Motor Skills With Functional Dexterity Test in Children With ADHD and Comparison With Healthy Controls
Authors: Akkaya Nuray , Kabukçu Başay Bürge , Urak Özkan , Başay Ömer , Şahin Füsun 
Published: December 2024

Objective: The study aimed to investigate whether the fine motor skills measured by the Functional Dexterity Test (FDT) in ADHD children differ from healthy controls. The second aim was to assess the applicability of the FDT assessment method among ADHD children. Method: The FDT results as an objective assessment of hand skills were compared between 7 and 17 years old ADHD cases ( n = 146) and age and gender-matched healthy controls ( n = 213). Results: We found lower dominant and non-dominant processing time (respectively for dominant hand and non-dominant hand p = .001, effect size Cliff’s Delta = .22; p = .001, ES Cliff’s Delta = .29), higher peg processing speed ( p = .001, ES Cliff’s Delta = .23; p = .001, ES Cliff’s Delta = .29), higher total error ( p = .001, ES Cliff’s Delta = .40; p = .001, ES Cliff’s Delta = .51), and total FDT time ( p = .0017, ES Cliff’s Delta = .14; p = .011, ES Cliff’s Delta = .16) in ADHD patients compared to healthy controls. Conclusion: Manual dexterity evaluation would be helpful to detect the fine motor skill deficits of ADHD children. Although ADHD children were advantageous regarding speed, they were disadvantageous regarding processing errors and total process time. Therefore, the error time data should be considered in evaluating ADHD children, unlike healthy children.
Phylodynamic Investigation of Yellow Fever Virus Sheds New Insight on Geographic Dispersal Across Africa
Authors: Motayo Babatunde Olanrewaju , Opayele Adewale , Akinduti Paul Akiniyi , Faneye Adedayo Omotayo , Omoregie Isibor Patrick 
Published: December 2024

Background: Molecular epidemiology has shown the presence of four genotypes circulating across Africa, a paucity of data exists regarding phylogeography of the African Yellow fever (YF) genotypes. The need to fill this gap with spatiotemporal data from continuous YF outbreaks in Africa conceptualized this study; which aims to investigate the most recent transmission events and directional spread of yellow fever virus (YFV) using updated genomic sequence data. Methods: Yellow fever sequence data was utilized along with epidemiologic data from outbreaks in Africa, to analyze the case/fatality distribution and genetic diversity. Phylodynamic and phylogeographic were utilized to investigate ancestral history, virus population dynamics, and geographic dispersal of yellow fever across Africa. Results: There was a sharp increase in laboratory confirmed cases after year 2015, with Nigeria and the Democratic Republic of Congo having the highest numbers of cases. Phylogeny of the YF genotypes followed a previously reported pattern with distinct geographic clustering. Historical dispersal of YFV was discovered to have occurred from West into Central/East Africa, with recent introductions occurring in West Africa. Conclusions: We have shown the continuous circulation of YF in Africa, with distinct genotype distributions within the west and central African sub-regions. We have also shown the potential contribution of African genotypes, in the historical dispersal of yellow fever. We advocate for expanded and integrated molecular surveillance of YFV and other Arboviruses in Africa.
Multi-epitope Based Peptide Vaccine Candidate Against Babesia Infection From Rhoptry-Associated Protein 1 (RAP-1) Antigen Using Immuno-Informatics: An In Silico Approach
Authors: Malgwi Samson Anjikwi , Adeleke Victoria T , Adeleke Matthew Adekunle , Okpeku Moses 
Published: December 2024

Objective: Babesiosis is a significant haemoparasitic infection caused by apicomplexan parasites of the genus Babesia. This infection has continuously threatened cattle farmers owing to its devastating effects on productivity and severe economic implications. Failure to curb the increase of the infection has been attributed to largely ineffective vaccines. This study was designed to develop a potential vaccine candidate. Method: Rhoptry-associated protein-1 (RAP-1) was used to identify and design a potential multi-epitope vaccine candidate due to its immunogenic properties through an immunoinformatics approach. Results and conclusions: A multi-epitope vaccine comprising 11 CD8+, 17 CD4+, and 3 B-cell epitopes was constructed using the AAY, GPGPG, and KK linkers. Beta-defensin-3 was added as an adjuvant to potentiate the immune response using the EAAK linker. The designed vaccine was computationally predicted to be antigenic (antigenicity scores: 0.6), soluble (solubility index: 0.730), and non-allergenic. The vaccine construct comprises 595 amino acids with a molecular weight of 64 152 kDa, an instability and aliphatic index of 13.89 and 65.82, which confers stability with a Grand average of hydropathicity (GRAVY) value of 0.122, indicating the hydrophobicity of the construct. Europe has the highest combined class population coverage, with a percentage of 96.07%, while Central America has the lowest population coverage, with a value of 22.94%. The DNA sequence of the vaccine construct was optimized and successfully cloned into a pET-28a (+) plasmid vector. Analysis of binding interactions indicated the stability of the complex when docked with Toll-like receptor-2 (TLR-2). The subunit vaccine construct was predicted to induce and boost sufficient host cellular and humoral responses in silico. However, further experimental research and analysis is required to validate the findings. Limitation: This study is purely computational, and further experimental validation of these findings through in vivo and in vitro conditions is required.
Association between plant-based dietary patterns and cognitive function in middle-aged and older residents of China
Authors: Peng Jianying , Li Xiaolong , Wang Jie , Li Fengping , Gao Jianfeng , Deng Yan , Li Benchao , Li Tingting , Li Yuanyuan , Tang Sui , Lu Likang , Zhou Peiyang , Rong Shuang 
Published: December 2024

Background Plant-based diets may protect against cognitive impairment; however, observational data have not been consistent. Objective This study aimed to evaluate the association between plant-based dietary patterns and cognitive function. Methods The study recruited 937 participants who were asked to complete food frequency questionnaires to assess the quality of their plant-based diets using the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Cognitive function evaluated using the Montreal Cognitive Assessment (MoCA) test. Logistic regression was used to explore the association between plant-based dietary patterns and the prevalence of mild cognitive impairment (MCI), while multiple linear regression was used to analyze the association between plant-based dietary patterns and cognitive scores. Results The prevalence of MCI was 26% among the 937 participants. There was a significant association between higher uPDI scores and higher odds of MCI, with Quintile 4 compared with Quintile 1 showing an odds ratio of 2.21 (95% confidence interval 1.35, 3.60). Higher uPDI scores were associated with a lower total MoCA score and poorer performance in various cognitive domains. There were no significant associations between the PDI, the hPDI, and cognitive function. Consuming whole grains, nuts, and eggs once a week or more were associated with a lower risk of MCI, whereas frequently consumption of pickled vegetables was associated with an increased risk of MCI. Conclusions Unhealthy plant-based diets were associated with cognitive impairment, while whole grains, nuts, and eggs may protect cognitive function; pickled vegetables are associated with cognitive impairment.
Factors influencing rates of unsupervised assessment of short-term learning in cognitively unimpaired adults
Authors: Lim Yen Ying , Mills Andrea , Norfolk Maya , Rosenich Emily , Maruff Paul 
Published: December 2024

Background In older adults with preclinical Alzheimer's disease (AD), learning curves derived from validated psychological learning paradigms are reduced to an extent greater than impairment, or decline, on neuropsychological memory tests. Objective This study aimed to examine how age, sex, education, mood, and general dementia risk, which also increases risk for preclinical AD, could influence learning curves. Methods 1050 adults enrolled in the BetterBrains trial completed 10 blocks of ORCA-LLT learning trials over 5 days. Learning curves were derived from improvement in accuracy over trials. Participants also completed questionnaires of demography and mood, and the CAIDE risk score was computed for each participant. Results Most participants (67%) completed ≥6 blocks of ORCA-LLT. Older age (d = 0.75), lower education (d = 0.50), and higher dementia risk (d = 0.36) were associated significantly with slower learning rates. Conclusions In older adults, learning curves are influenced subtly by age, education, and dementia risk but not by sex or mood.
Associations between antidiabetic medications and cerebrospinal fluid biomarkers of Alzheimer's disease
Authors: García-Lluch Gemma , Marseglia Anna , Royo Lucrecia Moreno , Albiach Juan Pardo , Garcia-Zamora Mar , Baquero Miquel , Peña-Bautista Carmen , Álvarez Lourdes , Westman Eric , Cháfer-Pericás Consuelo 
Published: December 2024

Background It has been hypothesized that insulin resistance is pivotal in mediating amyloid and tau dysregulations in Alzheimer's disease (AD). Objective To investigate the impact of different antidiabetic agents, their daily dosage intake, and treatment duration on cerebrospinal fluid (CSF) AD biomarkers among patients with type 2 diabetes. Methods This cross-sectional study selected patients between 50 and 80 years with diabetes and CSF AD biomarkers screened between 2017 and 2023 in the VALCODIS Cohort. CSF biomarkers were total tau (t-tau), phosphorylated tau 181 (p-tau), and amyloid-β 42 (Aβ42). Analytical variables were obtained. Antidiabetic prescriptions were recorded in defined daily doses (DDD), according to the ATC/DDD 2021 system, and years of drug exposure duration before lumbar puncture. Logistic regressions were performed to establish the correlations between drug usage and AD biomarker alteration. Results Among patients with diabetes, Insulin consumption was associated with lower odds of abnormal Aβ42 levels (OR 0.36 [95% CI 0.15, 0.76]) and tau pathology (OR 0.49 [95% CI 0.24–0.98]). Metformin was related to lower odds of pathological p-tau when diabetes was uncontrolled, acting on t-tau and t-tau/Aβ42 ratio when it was concomitant with insulin, and patients had controlled diabetes. Lower odds of pathological levels of tau were observed when additional oral antidiabetic drugs were added among metformin users. iSGLT2 was associated with tau pathology. Conclusions The impact of antidiabetics on AD-related pathological biomarkers may depend on diabetes management.