bluuebunny/crossref_metadata_2025 huggingface dataset:
Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data
Authors: Guccione Caitlin , Patel Lucas , Tomofuji Yoshihiko , McDonald Daniel , Gonzalez Antonio , Sepich-Poore Gregory D. , Sonehara Kyuto , Zakeri Mohsen , Chen Yang , Dilmore Amanda Hazel , Damle Neil , Baranzini Sergio E. , Hightower George , Nakatsuji Teruaki , Gallo Richard L. , Langmead Ben , Okada Yukinori , Curtius Kit , Knight Rob
Published: January 2025

As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples. We find that these methods are important for obtaining accurate results in low biomass samples (e.g., tissue, skin). Overall, we demonstrate that rigorous host filtration is a key component of privacy-minded analyses of patient microbiomes and provide computationally efficient pipelines for accomplishing this task on large-scale datasets.
Association between wide-ranging food intake and Parkinson’s disease: a comprehensive mendelian randomization study
Authors: Su Yana , Hao Yulei , Dong Wanhui , Qiu Ruqing , Zhang Ying
Published: January 2025

Parkinson’s disease (PD) is a complex neurodegenerative disorder influenced by both genetic and environmental factors, including dietary habits. Despite considerable research, the relationship between food intake and PD risk remains poorly understood. Here, we conducted a comprehensive Mendelian randomization analysis to investigate the association between a wide spectrum of food intake and PD risk. Utilizing data from large-scale genome-wide association studies (GWAS) and dietary databases, we constructed genetic instruments for various dietary factors, including fruit, vegetable, meat, fish, dairy, and grain intake, among others, totaling 170 different food items. Using multivariable inverse variance weighted methods, we found a causal relationship between Mozzarella intake and Parkinson’s disease (odds ratio [OR] = 9.83, 95% confidence interval [CI] = 2.52–38.34, P-value < 0.05). Additionally, a causal relationship was observed between Pancake intake and Parkinson’s disease (odds ratio [OR] = 0.20, 95% confidence interval [CI] = 0.07–0.59, P-value < 0.05). Furthermore, our reverse Mendelian randomization analysis and multivariable Mendelian randomization analysis provided further support for these findings. To our knowledge, we are the first to investigate the causal relationship between the broad intake of 170 different food items and Parkinson’s disease. Our study reveals the causal relationships between Pancake intake, and Mozzarella intake with Parkinson’s disease.
Translation and validation of the meat attachment questionnaire (MAQ) in a French general practice population
Authors: Delaunay Bruno , Tudrej Benoit , Bernard Augustin , Dupuy Alexandra , Malavergne Claire , Bacon Trystan , Sebo Paul , Maisonneuve Hubert
Published: January 2025

Meat consumption has significant implications for both individual health and the environment. Understanding individuals’ attachment to meat is crucial for designing effective interventions to reduce consumption. The MAQ is a tool developed to assess individuals’ attachment to meat. This study aims to translate and validate the MAQ into French for use in a general practice population in France. The study was conducted in three phases: translation, pretesting through cognitive interviews, and testing through a cross-sectional study of general practice patients. Descriptive, factorial, and internal consistency analyses were performed to validate the French version of the MAQ. The French version of the MAQ consists of 17 items in four dimensions: Hedonism, Affinity, Entitlement, and Dependence. Face validity was confirmed by cognitive interviews. The RMSEA and CFI were 0.06 and 0.92 respectively, showing acceptable goodness-of-fit. Internal consistency was demonstrated with Cronbach’s alpha and Loevinger’s H coefficients exceeding 0.7 and 0.3, respectively. The French version of the MAQ is a valid and reliable tool for assessing individuals’ attachment to meat in a general practice population. Its application shows promise for the design of targeted interventions to reduce meat consumption, benefiting both individual health and environmental sustainability.
Advanced IoT-integrated parking systems with automated license plate recognition and payment management
Authors: Pradhan Gulmini , Prusty Manas Ranjan , Negi Vipul Singh , Chinara Suchismita
Published: January 2025

Urban parking management is a growing challenge with increasing vehicle numbers and limited parking space. Traditional methods often fail during peak hours, leading to inefficiencies, unauthorized usage, and revenue losses. For instance, a parking lot designed for 300 vehicles often exceeds 90% occupancy during peak times, creating congestion and billing inaccuracies. This research proposes an automated system integrating sensors, image processing, and database management to address these issues. A single camera monitors multiple parking slots, with predefined coordinates linked to IR sensors for dual verification. Image processing algorithms, including Optical Character Recognition (OCR), enable accurate license plate recognition. Testing under real-world conditions showed 95% accuracy in daylight, 90% in low light, and 93% for plates at 45-degree angles. Detection accuracy reached 88% at distances of 1.5–3 m, ensuring reliable operation even at the camera’s range limits. Occupancy tracking achieved less than a 5% error margin compared to manual methods, while the fare calculation module reduced billing errors by 90%, enhancing efficiency and revenue. The system’s scalable design supports applications in parking management, toll collection, and traffic monitoring. By improving vehicle detection, occupancy tracking, and billing accuracy, this solution addresses critical challenges in urban parking and contributes to smarter city infrastructure.
Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition
Authors: Kim Min Jung , Yang Ye Jin , Min Ga-Yul , Heo Ji Woong , Son Jae Dong , You Young Zoo , Kim Hun Hwan , Kim Gon Sup , Lee Hu-Jang , Yang Ju-Hye , Park Kwang Il
Published: January 2025

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and excessive cytokine production. This study aimed to explore the potential of Camellia sinensis L. water extract (CSE) as a treatment for AD by the impact of CSE on inflammatory responses in keratinocytes, particularly concerning the production of inflammatory cytokines and the modulation of signaling pathways relevant to AD pathogenesis. CSE was obtained via hot water extraction from Camellia sinensis L. Ultra-high-performance liquid chromatography (UPLC) analyzed catechin and caffeine content. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), polyphenol and flavonoid content were determined. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay measured antioxidant activity. Enzyme-Linked Immunosorbent Assay (ELISA), western blotting, and Immunofluorescence (IF) assays examined cytokines, pathways, and protein localization, respectively. Molecular docking assessed compound binding with inflammation-related proteins. UPLC identified six CSE components including epigallocatechin (EGC) epicatechin (EC), caffeine (CF), catechin (C), epigallocatechin gallate (EGCG), and epicatechin gallate (ECG). CSE demonstrated a significant reduction in the production of inflammatory cytokines interleukin (IL)-2 and IL-6 in TNF-α/IFN-γ activated keratinocytes. Treatment with CSE inhibited the mitogen-activated protein kinase (MAPK) pathway, which resulted in decreased phosphorylation of p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Exposure of TNF-α/IFN-γ- stimulated human keratinocytes (HaCaT) cells to CSE resulted in a 200 µg/mL dependent inhibition of p65 and signal transducer and activator of transcription 1 (STAT-1) translocation from the cytosol to the nucleus, as confirmed through immunofluorescence (IF) staining. Molecular docking simulations provided insights into the underlying mechanisms of CSE action, which supported its potential as a therapeutic agent for AD. CSE might be a potential candidate for its therapeutic efficacy for inflammatory skin conditions like AD. Thus, based on this evidence, the authors suggest that CSE should be studied further for its anti-inflammatory activities and topical application in the treatment of AD.
Three-dimensional imaging of topologically protected strings in a multiferroic nanocrystal
Authors: Najeeb Mansoor A. , Serban David , Porter Daniel G. , Lichtenberg Frank , Collins Stephen P. , Bombardi Alessandro , Spaldin Nicola A. , Newton Marcus C.
Published: January 2025

Multiferroic materials can host a plethora of intriguing phenomena due to the presence of multiple ferroic properties that break both spatial inversion symmetry and time reversal symmetry at an observable scale. Hexagonal manganite multiferroics are of particular interest as the properties of their symmetry-lowering phase transition can be described by a Mexican-hat-like potential energy surface. The early universe is proposed to have undergone a symmetry-lowering phase transition that is described by a similar Mexican-hat-like potential that gives rise to the formation of one-dimensional topologically protected defects known as cosmic strings. According to the Kibble-Zurek mechanism, hexagonal manganite multiferroics can host the crystallographic equivalent of cosmic strings and can therefore serve as a testing ground for exploration of concepts in cosmology. To date, however, direct imaging of 1D topological defects in a condensed matter material system has not been achieved. Here we report on robust three-dimensional imaging of topologically protected strings in a single hexagonal manganite nanocrystal, enabled by advances in experimental techniques. Our findings reveal multiferroic strings with a preferred phase vortex winding direction and average separation of  ~93 nm.
Piecewise pulse‐width modulation for neutral‐point current reduction in NPC inverter
Authors: Savastianov Mikhail , Smedley Keyue
Published: January 2025

Effective neutral‐point balancing in a neutral‐point‐clamped inverter can yield substantial benefits, including cost reduction and efficiency improvement for the system. This article proposes a new piecewise pulse‐width modulation designed to reduce low‐frequency oscillations of the neutral‐point current without compromising the inverter power losses. The proposed piecewise modulation is simple to implement as it has one reference signal per phase. The performance of the proposed modulation is validated through comprehensive comparisons with alternative methods. The obtained simulation and experimental results demonstrate the effectiveness of the proposed piecewise modulation.
Inexpensive SAR testbed for 3D mmWave imaging applications
Authors: Mahbub S M Yahea , Dawood Muhammad , Shareef Ehtesham
Published: January 2025

In this paper, the authors investigate and develop a low‐cost synthetic aperture radar (SAR) testbed and utilise it to capture and reconstruct high‐resolution 3D mmWave SAR images. Despite much attention from both industrial and academic scholars, cost restraints and complexity have hindered the deployment of SAR systems, particularly in the mmWave domain. This paper outlines the major components and systems of the 3D SAR testbed. The authors build a testbed with low‐cost, commercially available hardware components and include open‐source software that is highly reconfigurable and simple to reproduce. The multiple‐input multiple‐output (MIMO) radar sensor uses a frequency‐modulated continuous wave (FMCW) chirp at the V‐band (40–75 GHz) and synthesises a rectilinear two‐dimensional planar aperture. The authors presented several reconstructed 3D images imitating real‐world scenarios using the testbed. A non‐linear sampling technique that has significantly decreased the amount of time required for data acquisition was implemented. In addition, the authors employed multiple image quality metrics to quantify and compare the images produced by the testbed. The testbed can be used to test and validate new techniques and algorithms.
Irradiated Homologous Costal Cartilage Grafts in Complex Functional Septorhinoplasty
Authors: Jama Guled M. , Bhanwala Sindhuja , Pericleous Agamemnon , Acharya Vikas , Unadkat Samit N. , Randhawa Premjit S. , Andrews Peter J.
Published: January 2025

Optimal results in complex nasal reconstruction, particularly in the context of post-traumatic and revision septorhinoplasty, often require the use of cartilage grafts to provide additional structural support to the nose. While autologous costal cartilage (ACC) has been traditionally used, this can be limited by donor site morbidity, increased operative time, and in some cases, lack of suitable cartilage for grafting. There has been a trend towards using irradiated homologous costal cartilage (IHCC) as an alternative source of graft material. We review our departmental experience of using IHCC in functional septorhinoplasty surgery. We performed a retrospective review of electronic medical records of all patients who underwent septorhinoplasty using IHCC at a tertiary referral center between May 1, 2022, and April 30, 2024. Demographic data, surgical details, and postoperative outcomes, including rates of infection, resorption, warping, and revision were recorded and analyzed. Fifty-seven patients (34 males, 23 females) with a mean age of 41.0 years (range: 18–65 years) were included. Forty-one were revision septorhinoplasty operations, while 16 were primary cases. Almost all were performed via an open approach (98.2%). Three patients developed postoperative infection (5.3%) while one developed columellar dehiscence needing further revision surgery (1.8%). Functional and aesthetic results were otherwise satisfactory in all patients. We observed no cases of warping, resorption, or extrusion. The median length of follow-up was 279 days (interquartile range: 171–527 days). We present the largest United Kingdom series to date on the use of IHCC in septorhinoplasty surgery. Our findings support its use as a safe and effective graft material and a viable alternative to autologous sources, offering the benefits of a robust reconstructive material and shortened operative time, without the risk of donor site complications. A longer follow-up period is ideally required to evaluate its long-term structural stability.
Autogenous Block Graft with Simultaneous Implant Placement in the Aesthetic Zone: A Case Report
Authors: Heriasti Maudina Dwi , Yunial Muhammad Aryaditha , Mahendra Tri Ardi , Julia Vera , Sulistyani Lilies Dwi , Utomo Yudy Ardilla
Published: January 2025

Osseus defects in the alveolar ridge can occur from trauma events, periodontal disease, and infections. Reconstruction of osseus defects requires bone augmentation, which is a crucial component of dental implant procedures, particularly in the aesthetic zone where the availability of sufficient bone volume can be a challenge. The symphysis block graft is a technique that has gained popularity in recent years for bone augmentation, by harvesting a small section of bone from the mandible. The standard procedure usually takes up to 3 to 6 months of a waiting period for implant placement after a bone graft procedure; however, it is not impossible to simultaneously do the single stage surgery of block graft and implant placement in the aesthetic zone. This article aims to evaluate the outcome of autogenous block graft with simultaneous implant placement procedure in the aesthetic zone in one single visit. A 21-year-old man presented with an edentulous area in the upper front teeth and wanted to get tooth replacements of his missing central and left incisors. The front teeth were avulsed and extracted after a road traffic accident 3 months earlier, and the treatment given was a closed reduction with arch bars for 2 months. The osseus defects in labio-palatal width was reconstructed with a symphysis block graft as the donor and two implants were inserted into the recipient site in a single stage surgery. A single stage surgery involving an autogenous block graft with simultaneous implant placement is an effective technique and can be considered safe with a high survival rate. However, further studies with long-term evaluations need to be conducted to provide more evidence to support this protocol.
Pedicled Abdominal Flap in the Youngest Patient Yet? A Case Report of a Newborn with Neonatal Compartment Syndrome
Authors: Sabapathy S. Raja , Dharanipriya A. , Mohan Monusha , Ramani Subramanian , Selvaraj M. , Shanmuga Krishnan R. Raja
Published: January 2025

Pedicled abdominal flaps continue to be popular in most parts of the world for covering soft tissue defects of the upper limb. There is apprehension if distant pedicled flaps can be used in children for fear of disruption. We recently had a newborn baby with neonatal compartment syndrome (NCS) of her left upper limb in whom a pedicled abdominal flap was successfully used to cover the raw area in the forearm at 41 days of life. A severely swollen limb with ischemic skin lesions associated with lack of motion of the upper limb often points to NCS. Since no guidelines exist for the diagnosis and management of NCS, a high index of suspicion and urgent fasciotomy are required to limit its sequelae. Our patient had an emergency fasciotomy elsewhere was referred to us with a precariously viable limb for salvage. The raw area in the forearm with exposed bone was successfully covered with a pedicled abdominal flap at 41 days of life. Our patient is probably the youngest patient ever to receive a pedicled abdominal flap.
Green growth dynamics: unraveling the complex role of financial development and natural resources in shaping renewable energy in Sub-Saharan Africa
Authors: Osman Alhasan , Afjal Mohd , Alharthi Majed , Elheddad Mohamed , Djellouli Nassima , He Zhang
Published: January 2025

This study examines the complex interplay between financial development, natural resources, and renewable energy consumption in Sub-Saharan Africa from 2000 to 2020, highlighting the pivotal role of financial strategies in enhancing sustainable energy practices. Employing an array of analytical techniques, including panel-corrected standard errors (PCSE), fixed effects, random effects models, and panel-fixed quantile regression, we delve into the nuanced relationships among these critical variables. The findings reveal that while natural resources and financial development generally exert negative impacts on renewable energy consumption when considered in isolation, a significant transformation occurs when these factors interact. Specifically, the detrimental effects of natural resources on renewable energy usage are substantially mitigated by robust financial development, which not only offsets the negative impacts but also promotes renewable energy adoption. This interaction points to a synergistic relationship where strategic financial development can leverage natural resources for progressive energy outcomes. Such insights underscore the necessity of well-coordinated financial policies and resource management to foster green growth in Sub-Saharan Africa, demonstrating the urgent need for integrated approaches to achieve sustainability in the region. This research not only clarifies the dynamics of financial and natural resource interdependencies but also motivates significant policy implications for enhancing renewable energy landscapes in developing economies.
Chickpea (Cicer arietinum) genetic diversity: genetic resources, breeding progress, and future prospects
Authors: Shahnaz Zeba , Shahnaz Arooba , Ismail Asif , Manzoor Zahid , Iqbal Rashid , Zia Muhammad Abu Bakar
Published: January 2025

Chickpea (Cicer arietinum) is the third most significant grain legume grown in dry and semi-arid regions. Ensuring global food security necessitates sustainable practices, such as improving agricultural productivity with cultivars that provide increased yields and adaptability. The major limits on chickpea production are poor genetic diversity, low and variable yield, and vulnerability to biotic and abiotic stresses. Despite the abundance of germplasm accessions, their impact on improving chickpea genetics has been limited. Combining contemporary genomic resources with conventional breeding techniques holds the potential to develop climate-resilient chickpea varieties. To close the genome-to-phenome gap, contemporary genomic technology must be integrated with molecular breeding initiatives. Furthermore, major genetic resources, such as molecular markers and transcript sequences, have been identified. Recent advances in genomic methods and technologies have eased large-scale sequencing and genotyping in chickpea as well as in other crops. These tools are intended to help identify trait-specific germplasm, map phenotypes, and mine alleles for biotic and abiotic stress tolerance, as well as agronomic qualities. This review focuses on recent improvements that have opened new opportunities for establishing and screening breeding populations and tactics for improving selection efficiency and speeding genetic gain in chickpea.
Natural genetic adaptation allows flexible reproductive behaviour: the case of wild carrot (Daucus carota L. subsp. carota) vs cultivated carrot (Daucus carota L. subsp. sativus)
Authors: Godwin Asharp , Pieralli Simone , Sofkova-Bobcheva Svetla , McGill Craig
Published: January 2025

Context Comparing the life cycles of wild and cultivated carrots is vital for identifying any overlapping flowering periods, as wild carrots have the potential to compromise the genetic purity of commercial carrot seeds via pollen flow. However, little information is known about how juvenility, vernalization, and their interactions impact the flowering pattern of wild and cultivated carrots in New Zealand. Aims We evaluated the influence of different juvenile phases, and vernalization phases on floral characteristics and flowering behaviour of cultivated and wild carrots. Methods The study was a factorial randomized complete block design with four blocks of five plants per block, incorporating treatments of different carrot genotypes (G1, cultivated; G2, wild carrots), juvenile phases (J1, 12 weeks; J2, 8 weeks; J3, 4 weeks), and vernalization phases (V1, 12 weeks; V2, 4 weeks; V3, no vernalization). Flowering percentage, flowering time, percentage of overwinter survival, and floral traits, including number of umbels and branches, and height of floral stem were recorded and analyzed by ANOVA. Key results Cultivated carrots flowered only when exposed to 12 weeks vernalization, while wild carrots have shown 100% flowering across all treatment combinations. Wild carrots exhibited a higher overwintering survival rate (94.9–100%) than cultivated carrots (66.1–98.3%). Prolonged exposure to vernalization significantly affected the floral traits of wild carrots. Conclusions There is a high likelihood of overlapping flowering periods between wild and cultivated carrots, as wild carrots can survive as both winter and summer annuals. Implications To avoid undesirable pollen flow during overlapping flowering periods of wild and cultivated carrots, we recommend timely weed management strategies to control wild carrots.
CATI++: empirical study and evaluation for adjacent instruction enhanced type inference
Authors: Chen Ligeng , He Zhongling , Qian Yi , Mao Bing
Published: January 2025

Variable-type information is fundamental, and it greatly helps in understanding the program semantics. Previous work applies rule-based and machine learning-based methods to recover variable types from commercial off-the-shelf binaries, heavily relying on the data flow or control flow. However, according to our study, about half of the variables lacked or even had no data flow; this problem has not received much attention from previous work. We empirically explore the severity of this problem to the type inference task and analyze its root causes. Based on compilation properties, we find that the instructions surrounding the instructions that operate on variables provide good contextual information that can be used for co-encoding to overcome the above problem. In this paper, we present an effective machine learning-based method to infer variable types and overcome the challenge of limited data dependency via adjacent instructions co-encoding. Therefore, we implement a system called CATI++, which locates variables from stripped binaries and infers 19 types of variables. We evaluate CATI++ on different compilation options, all of which outperforms state-of-the-art methods. The ablation experiments verify that our scheme is not sensitive to compilation conditions, while our designed method effectively alleviates the problems caused by missing data dependency.
Systematic review on definitions of intestinal ultrasound treatment response and remission in inflammatory bowel disease
Authors: Allocca Mariangela , D’Amico Ferdinando , Fiorino Gionata , Jairath Vipul , Kucharzik Torsten , Peyrin-Biroulet Laurent , Danese Silvio
Published: January 2025

Background

Intestinal ultrasound (IUS) is emerging as a valuable tool to assess treatment response in inflammatory bowel disease (IBD) clinical trials. This study details how IUS defines response and remission to evaluate treatment efficacy in IBD patients.

Methods

We conducted a comprehensive search of studies from 1984 to March 31, 2024, focusing on IUS use in assessing treatment efficacy in IBD.

Results

A total of 51 studies were included: 31 on Crohn’s disease (CD), 12 on ulcerative colitis (UC) and 8 on IBD. Ileocolonoscopy was used as a reference standard in 53% of studies. IUS-defined response was reported in 47% of studies, with the majority (71%) using changes in bowel wall thickness (BWT) and color Doppler signals (CDS) as key indicators. IUS-defined remission was reported in 53% of studies, primarily using normalization of BWT to <3 mm and CDS to grades 0 or 1 as criteria. Ultrasonographic activity scores were used in 16% of studies, including the Bowel Ultrasound Score (BUSS) in two CD studies, the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in one CD study, and the Milan Ultrasound Criteria (MUC) in one UC study The remaining four studies used unvalidated scores without clear definitions of response or remission. Assessment times varied, most commonly at weeks 8–16, and at 6, 12, and 24 months.

Conclusions

This systematic review reveals significant variability in IUS definitions of response and remission in IBD, highlighting the need to standardize eligibility criteria and outcome measures for IUS in IBD clinical trials.
Fighting for Lemons: The Balancing Effect of Private Information on Incentives in Dynamic Contests
Authors: Möller Marc
Published: January 2025

In a common value environment with multi-stage competition, losing a stage conveys positive news about a rival’s estimation of a contested prize, capable of balancing the discouraging effect of falling behind. We show that, due to players’ learning from stage-outcomes, aggregate incentives under private information are often greater than under public information and may even exceed the static competition benchmark. Moreover, laggards can become more motivated than leaders, giving rise to long-lasting fights. Our results have implications for the duration of R&D races, the desirability of feedback in labor- and procurement-contests, and the campaign spending and selective efficiency of presidential primaries.
Drought tolerance as an evolutionary precursor to frost and winter tolerance in grasses
Authors: Schat Laura , Schubert Marian , Fjellheim Siri , Humphreys Aelys M
Published: January 2025

Accumulating evidence is suggesting more frequent tropical-to-temperate transitions than previously thought. This raises the possibility that biome transitions could be facilitated by precursor traits. A wealth of ecological, genetic, and physiological evidence suggests overlap between drought and frost stress responses, but the origin of this overlap, i.e., the evolution of these responses relative to each other, is poorly known. Here, we test whether adaptation to frost and/or severe winters in grasses (Poaceae) was facilitated by ancestral adaptation to drought. We used occurrence patterns across Köppen–Geiger climate zones to classify species as drought, frost, and/or winter tolerant, followed by comparative analyses. Ancestral state reconstructions revealed different evolutionary trajectories in different clades, suggesting both drought-first and frost-first scenarios. Explicit simultaneous modelling of drought and frost/winter tolerance provided some support for correlated evolution, but suggested higher rates of gain of frost/winter tolerance in drought-sensitive rather than drought-tolerant lineages. Overall, there is limited support across grasses as a whole that drought tolerance acted as an evolutionary precursor to frost or severe winter tolerance. Different scenarios in different clades is consistent with present-day grasses being either cold or drought specialists, possibly as a consequence of trade-offs between different stress tolerance responses.
In vitro enzyme characterization and several inhibitors for monkeypox virus core protease I7L
Authors: Wei Lin , Wu Yuqi , Li Shuai , Weng Jun , Geng Miaomiao , Mei Meng , Wei Zigong
Published: January 2025

Monkeypox is a zoonotic viral disease caused by the monkeypox virus, a member of the genus Orthopoxvirus within the family Poxviridae, which also includes the variola virus. On 14 August 2024, WHO Director-General declared monkeypox outbreak a public health emergency of international concern. Similar to variola virus core protease K7L, I7L could be identified as a promising target to fight against monkeypox virus. Our work provides a solid foundation as well as specific molecular tools (protease production methods, assay design, inhibitor design) that can now be used to probe the function of I7L in vitro. Notably, in this work, various reported covalent lead compounds for COVID-19 proteases were screened and A68, shikonin, and myricetin were identified as exhibiting high inhibitory activity against I7L. This work not only sheds light on effective inhibitors for the monkeypox virus core protease but also contributes to the broader search for antiviral agents targeting this enzyme.
Reciprocal and non-reciprocal effects of clinically relevant SETBP1 protein dosage changes
Authors: Antonyan Lilit , Zhang Xin , Ni Anjie , Peng Huashan , Alsuwaidi Shaima , Fleming Peter , Zhang Ying , Semenak Amelia , Macintosh Julia , Wu Hanrong , Hettige Nuwan C , Jefri Malvin , Ernst Carl
Published: January 2025

Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells. We find that extremes of SETBP1 protein dose reciprocally influence important signalling molecules such as AKT, suggesting that the SETBP1 protein operates within a narrow dosage range and that extreme doses are detrimental. We identified SETBP1 nuclear bodies as interacting with the nuclear lamina and suggest that SETBP1 may organize higher order chromatin structure via links to the nuclear envelope. SETBP1 protein doses may exert significant influence on global gene expression patterns via these SETBP1 nuclear bodies. This work provides evidence for the importance of SETBP1 protein dose in human brain development, with implications for two neurodevelopmental disorders.
Lysine succinylome analysis of MRSA reveals critical roles in energy metabolism and virulence
Authors: Zhu Xiangqin , Min Hui , Tang Yishan , Gao Min
Published: January 2025

Methicillin-resistant Staphylococcus aureus’s (MRSA) resistance poses a global health challenge. This study investigates lysine succinylation in MRSA using proteomics and bioinformatics approaches to uncover metabolic and virulence mechanisms, with the goal of identifying novel therapeutic targets. Mass spectrometry and bioinformatics analyses mapped the MRSA succinylome, identifying 8048 succinylation sites on 1210 proteins. These analyses included Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein–protein interaction (PPI) network construction (e.g. using the STRING database, a widely used online tool for analyzing protein-protein interactions), providing a comprehensive functional and interactive landscape of succinylated proteins. The succinylated proteins were predominantly involved in cytoplasmic metabolic processes, with enrichment in glycolysis/gluconeogenesis and the tricarboxylic acid cycle. Both of these pathways are critical for MRSA’s energy production, growth, and virulence, supplying the necessary metabolic intermediates and energy to support bacterial survival and pathogenicity. Motif analysis revealed 13 conserved motifs, while PPI analysis highlighted fibronectin-binding protein A (FnbA) as a central virulence factor. Succinylation significantly influences MRSA’s metabolism and virulence, potentially impacting biofilm by modifying key proteins such as FnbA, bifunctional autolysin, and S-ribosylhomocysteine lyase(LuxS). These findings provide new avenues for developing antibiofilm strategies and therapeutic interventions against MRSA.
Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications
Authors: Lei Qi , Deng Hongkui , Sun Shicheng
Published: January 2025

Cell-based immunotherapy, recognized as living drugs, is revolutionizing clinical treatment to advanced cancer and shaping the landscape of biomedical research for complex diseases. The differentiation of human pluripotent stem cells (PSCs) emerges as a novel platform with the potential to generate an unlimited supply of therapeutic immune cells, especially when coupled with gene modification techniques. PSC-based immunotherapy is expected to meet the vast clinical demand for living drugs. Here, we examine recent preclinical and clinical advances in PSC-based immunotherapy, focusing on PSC gene modification strategies and differentiation methods for producing therapeutic immune cells. We also discuss opportunities in this field and challenges in cell quality and safety, and stresses the need for further research and transparency to unlock the full potential of PSC immunotherapies.
Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets
Authors: Kendsersky Nathan M , Odrobina Michal , Mabe Nathaniel W , Farrel Alvin , Grossmann Liron , Tsang Matthew , Groff David , Wolpaw Adam J , Narch Alaa , Zammarchi Francesca , van Berkel Patrick H , Dang Chi V , Mossé Yaël P , Stegmaier Kimberly , Maris John M
Published: January 2025

Background

Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods

We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets. Targets were validated with ChIP-sequencing, immunoblotting, and flow cytometry in neuroblastoma cell lines and isogenic ADRN-to-MES transition cell line models. Finally, we evaluated the activity of MES-specific agents in vivo and in vitro.

Results

Most immunotherapeutic targets being developed for neuroblastoma showed significantly higher expression in the ADRN subtype with limited expression in MES-like tumor cells. In contrast, CD276 (B7-H3) and L1CAM maintained expression across both ADRN and MES states. We identified several receptor tyrosine kinases (RTKs) enriched in MES-dominant samples and showed that AXL targeting with ADCT-601 was potently cytotoxic in MES-dominant cell lines and showed specific anti-tumor activity in a MES cell line-derived xenograft.

Conclusions

Immunotherapeutic strategies for neuroblastoma must address the potential of epigenetic downregulation of antigen density as a mechanism for immune evasion. We identified several RTKs as candidate MES-specific immunotherapeutic target proteins for the elimination of therapy-resistant cells. We hypothesize that the phenomena of immune escape will be less likely when targeting pan-neuroblastoma cell surface proteins such as B7-H3 and L1CAM, and/or dual targeting strategies that consider both the ADRN- and MES-cell states.
Kikuchi-Fujimoto disease: 6 years old boy rare case in Syria
Authors: Daoo Baseel Tawfik , Alhayek Shahd , Alakhrass Dana , Shibani Mosa , Khallouf Mohammad Samih
Published: January 2025

Kikuchi-Fujimoto disease (KFD) is a rare condition first identified in Japan in 1972. It typically presents with high fever and lymph node swelling, and may be linked to autoimmune conditions or viral infections. A 6-year-old boy presented with cervical enlargement and recurrent high fever. Physical examination revealed enlarged lymph nodes in the neck, axillary, and inguinal regions, along with hepatosplenomegaly. CT scans confirmed widespread lymphadenopathy, and blood tests showed elevated white blood cell count and C-reactive protein levels. Although lymphoma was suspected, biopsies indicated atypical lymphadenitis. Despite a positive Epstein–Barr virus test, no treatment was effective. Further lymph node biopsies ruled out lymphoma, EBV, and TB, ultimately confirming Kikuchi-Fujimoto Disease.
Disseminated fungal infection with Saprochaete capitata in acute myeloid leukemia patient: a case report from a developing country
Authors: Sweileh Mamoun W , Dawoud Ayman , Malhis Razan , Aiesh Banan M
Published: January 2025

Background: Saprochaete capitata may cause fatal infections in immunocompromised patients. This is the first case report of invasive Saprochaete capitate infection at an academic-tertiary care center in Palestine. Case presentation: We report a 36—year—old woman who presented with fever and severe neutropenia and was found to have AML/Non M3. While receiving her initial chemotherapy treatment, she encountered a rare fungal infection (Saprochaete capitata) that spread throughout her lungs, stomach, spleen, liver, and kidneys, presenting difficulties in both diagnosing and treatment. In addition to being treated with both voriconazole and amphotericin B, the patient underwent surgery to remove the infection source, resulting in a cure. Conclusion: In immunocompromised patients, Saprochaete capitata infection is frequently overlooked. It is essential to give antifungal combinations and to control the source of infection to enhance the outcome for patients.
Arising of autoimmune gastritis after helicobacter pylori eradication in an elderly female patient
Authors: Kiba Takayoshi , Nose Soichiro
Published: January 2025

Autoimmune gastritis (AIG) is a chronic condition in which the body’s immune system mistakenly attacks the stomach lining, specifically targeting parietal cells that produce stomach acid and intrinsic factors. After the H. pylori infection was eradicated, AIG developed in an elderly woman with symptoms of the disease. 1.5 years after eradication, esophagogastroduodenoscopy revealed remnants of the oxyntic mucosa sticky adherent dense mucus and scattered minute whitish protrusions at the greater curvature of the gastric corpus. Biopsy specimens from the greater curvature site of the gastric corpus before H. pylori eradication revealed neutrophilic cells in the superficial mucosa of the stomach that were mildly inflammatory and infiltrating. With the removal of H. pylori, the number of infiltrating inflammatory neutrophilic cells in the superficial mucosa decreased, whereas that of infiltrating lymphocytes increased in the sub-superficial mucosa. This case suggests that further studies regarding the detailed time course of AIG are required.
A single giant frontoparietal intraaxial hydatid cyst in a 5-year-old female: a case report and review of literature
Authors: AL-Ihribat Alaa R , Qunaibi Yaman N , Amro Rawand B , Ahmed Jamal , Rije Rama F , Shalalfeh Husam , Ibedo Falah , Itkaidek Saeed
Published: January 2025

Echinococcus larval stage or a hydatid cyst, a parasitic disease that passes from animals to humans. Echinococcus granulosus and, less commonly, Echinococcus multilocularis species cause the disease. Intracranial echinococcosis is rare, with an incidence of approximately 1%–2%. Primary and secondary intracranial hydatid cysts can be found. A primary one, the most common type, is always solitary. CT and MRI have significantly contributed to the accurate diagnosis of hydatids. Surgical removal of the cyst is the treatment of choice, resulting in most cases in a complete recovery. In this report, we aim to emphasize the presentation of such an isolated primary cerebral hydatid cyst in a 5-year-old girl with neurological symptoms of a space-occupying lesion. Radiology revealed a giant left frontoparietal hydatid cyst. A cerebral hydatid cyst was operated on. The patient showed an uneventful recovery and was discharged. There was no recurrence at follow-up.
Circadian Misalignment Impacts Cardiac Autonomic Modulation in Adolescence
Authors: Morales-Ghinaglia Natasha , He Fan , Calhoun Susan L , Vgontzas Alexandros N , Liao Jiangang , Liao Duanping , Bixler Edward O , Fernandez-Mendoza Julio
Published: January 2025

Study Objectives

Although heart rate variability (HRV), a marker of cardiac autonomic modulation (CAM), is known to predict cardiovascular morbidity, the circadian timing of sleep (CTS) is also involved in autonomic modulation. We examined whether circadian misalignment is associated with blunted HRV in adolescents as a function of entrainment to school or on-breaks.

Methods

We evaluated 360 subjects from the Penn State Child Cohort (median 16y) who had at least 3-night at-home actigraphy (ACT), in-lab 9-h polysomnography (PSG) and 24-h Holter-monitoring heart rate variability (HRV) data. ACT-measured metrics of circadian misalignment included sleep midpoint (SM), sleep irregularity (SI), and social jetlag (SJL). Five 24-h, daytime and nighttime frequency- and time-domain HRV indices were the primary outcomes. Linear regression models adjusted for sex, race/ethnicity, age, body mass index, apnea/hypopnea index, sleep duration and its variability. These associations were also examined as a function of being in-school or on-break.

Results

While on-break, a later SM on weekends was significantly associated with all five nighttime HRV indices. While in-school, greater SI on weekdays was significantly associated with three daytime and three nighttime HRV indices. Greater SJL was not associated with any HRV index. Longitudinal analyses confirmed the association of adolescent SM, SI and SJL with change in nighttime HRV since childhood.

Conclusions

An irregular sleep phase during days of entrainment to social demands and a delayed sleep phase during ad-libitum days are associated with blunted HRV in adolescents. Circadian misalignment contributes to increased cardiovascular risk via an altered CAM in youth.
Didactic transposition of loan repayments in economics and the place of the discrete-continuous interplay
Authors: Milin Šipuš Željka , González-Martín Alejandro S , Bašić Matija
Published: January 2025

The study reported in this paper is motivated by an article published on a financial portal that presented loan repayments with a continuous approach, as opposed to the discrete approach of addressing loan repayments applied in mathematics courses for economists. Using the Anthropological Theory of the Didactic, we analyse the current didactic transposition of this content, based on a textbook for mathematics in economics and five interviews with teachers of mathematics and of economics, inquiring about their practices in teaching related to loan repayments in economics. The interviewed teachers indicated that this content is presented in a discrete way in mathematics courses for economics, although for reasons that do not seem directly connected to the content itself. Additionally, although the participants see the interest of considering the use of continuous variables and graphs, several constraints prevent them from their use in the context of loan repayments.
Quantifying protein unfolding kinetics with a high-throughput microfluidic platform
Authors: Atsavapranee B. , Sunden F. , Herschlag D. , Fordyce P.M.
Published: January 2025

Even after folding, proteins transiently sample unfolded or partially unfolded intermediates, and these species are often at risk of irreversible alteration (e.g.via proteolysis, aggregation, or post-translational modification). Kinetic stability, in addition to thermodynamic stability, can directly impact protein lifetime, abundance, and the formation of alternative, sometimes disruptive states. However, we have very few measurements of protein unfolding rates or how mutations alter these rates, largely due to technical challenges associated with their measurement. To address this need, we developed SPARKfold (Simultaneous Proteolysis Assay Revealing Kinetics of Folding), a microfluidic platform to express, purify, and measure unfolding rate constants for >1000 protein variants in parallel via on-chip native proteolysis. To demonstrate the power and potential of SPARKfold, we determined unfolding rate constants for 1,104 protein samples in parallel. We built a library of 31 dihydrofolate reductase (DHFR) orthologs with up to 78 chamber replicates per variant to provide the statistical power required to evaluate the system’s ability to resolve subtle effects. SPARKfold rate constants for 5 constructs agreed with those obtained using traditional techniques across a 150-fold range, validating the accuracy of the technique. Comparisons of mutant kinetic effects via SPARKfold with previously published measurements impacts on folding thermodynamics provided information about the folding transition state and pathways via φ analysis. Overall, SPARKfold enables rapid characterization of protein variants to dissect the nature of the unfolding transition state. In future work, SPARKfold can reveal mutations that drive misfolding and aggregation and enable rational design of kinetically hyperstable variants for industrial use in harsh environments.