bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis
Authors: Fang Jialing , Lei Jun , He Boxiao , Wu Yankang , Chen Peng , Sun Zaiqiao , Wu Ning , Huang Yafei , Wei Pengcheng , Yin Lei , Chen Yongshun 
Published: February 2024

AbstractResident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade.
The burden of disease in metachromatic leukodystrophy: results of a caregiver survey in the UK and Republic of Ireland
Authors: Thomas Sophie , Morrison Alexandra , Morton Georgina , Roberts Pat , Clark Vivienne , Imrie Jackie 
Published: February 2024

Abstract
Background
Metachromatic Leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease characterised by the progressive loss of motor function and severe decline in cognitive function. Limited information is available on the burden MLD places on patients and their families and the medical and social support these patients need. Three UK-based MLD patient organisations commissioned an online survey, and follow-up semi-structured interviews to describe and quantify these burdens across MLD subtypes, stage of disease (including end of life) and treatment status (untreated, gene therapy or hematopoietic stem cell transplant [HSCT]).

Results
A total of 24 patients were included in the study: thirteen late infantile (LI), six early juvenile (EJ), two late juvenile (LJ) and three adult onset (AO). Six patients had received gene therapy and one had received an HSCT. MLD patients receiving no disease modifying treatment bore a high symptom burden: 94% were wheelchair dependent, 88% required tube feeding, 88% were incontinent, 82% had lost their speech and all the children were either unable to attend education or needed specialist provision. Patients were reliant on numerous medical interventions and assistive equipment. All early-onset patients (LI and EJ) were wheelchair dependent, and tube fed, with all EJ patients having lost all speech. The caregiving responsibilities of parents impacted their employment, finances, relationships and health. Patients treated with gene therapy or HSCT were more mobile and were able to eat normally and two thirds of the children were able to attend mainstream school.

Conclusions
The impact of illness that patients and their caregivers faced was extensive, and the level of care, amount of medication, number of hospital visits and educational support required were substantial. Financial constraints often brought about by inability to work also placed considerable strain on families. The study increases understanding of the burden of MLD on patients and their families, and the level of unmet need in the treatment of the disease.
Analysis of the first ten years of FDA’s rare pediatric disease priority review voucher program: designations, diseases, and drug development
Authors: Mease Catherine , Miller Kathleen L. , Fermaglich Lewis J. , Best Jeanine , Liu Gumei , Torjusen Erika 
Published: February 2024

Abstract
Background
The Rare Pediatric Disease (RPD) Priority Review Voucher (PRV) Program was enacted in 2012 to support the development of new products for children. Prior to requesting a voucher, applicants can request RPD designation, which confirms their product treats or prevents a rare disease in which the serious manifestations primarily affect children. This study describes the trends and characteristics of these designations. Details of RPD designations are not publicly disclosable; this research represents the first analysis of the RPD designation component of the program.

Results
We used an internal US Food and Drug Administration database to analyze all RPD designations between 2013 and 2022. Multiple characteristics were analyzed, including the diseases targeted by RPD designation, whether the product targeted a neonatal disease, product type (drug/biologic), and the level of evidence (preclinical/clinical) to support designation. There were 569 RPD designations during the study period. The top therapeutic areas were neurology (26%, n = 149), metabolism (23%, n = 131), oncology (18%, n = 105). The top diseases targeted by RPD designation were Duchenne muscular dystrophy, neuroblastoma, and sickle cell disease. Neonatology products represented 6% (n = 33), over half were for drug products and 38% were supported by clinical data.

Conclusions
The RPD PRV program was created to encourage development of new products for children. The results of this study establish that a wide range of diseases have seen development—from rare pediatric cancers to rare genetic disorders. Continued support of product development for children with rare diseases is needed to find treatments for all children with unmet needs.
Impact of emergency physician performed ultrasound in the evaluation of adult patients with acute abdominal pain: a prospective randomized bicentric trial
Authors: Brau François , Papin Mathilde , Batard Eric , Abet Emeric , Frampas Eric , Le Thuaut Aurélie , Montassier Emmanuel , Le Bastard Quentin , Le Conte Philippe 
Published: February 2024

Abstract
Background
Abdominal pain is common in patients visiting the emergency department (ED). The aim of this study was to assess the diagnostic contribution of point-of-care ultrasound (POCUS) in patients presenting to the ED with acute abdominal pain.

Methods
We designed an interventional randomized, controlled, open label, parallel-group, trial in two French EDs. We included adult patients presenting to the ED with acute abdominal pain. Exclusion criteria were a documented end-of-life, an immediate need of life-support therapy and pregnant or breast-feeding women. Patients were randomized in the experimental group (i.e., workup including POCUS) or control group (usual care). The primary objective of the study was to assess the added value of POCUS on diagnostic pathway in the ED, according to the diagnostic established a posteriori by an adjudication committee. The primary endpoint was the proportion of exact preliminary diagnosis between the 2 groups. The preliminary diagnosis made after clinical examination and biological results with POCUS (intervention arm) or without POCUS (usual care) was considered exact if it was similar to the adjudication committee diagnosis.

Results
Between June 2021 11th and June 2022 23th, 256 patients were randomized, but five were not included in the primary analysis, leaving 125 patients in the POCUS group and 126 patients in the usual care group (130 women and 121 men, median [Q1-Q3] age: 42 [30;57]). There was no difference for exact diagnosis between the two groups (POCUS 70/125, 56% versus control 78/126 (62%), RD 1.23 [95% CI 0.74–2.04]). There was no difference in the accuracy for the diagnosis of non-specific abdominal pain nor number of biological or radiological exams. Diagnostic delays and length of stay in the ED were also similar.

Conclusions
In this trial, systematic POCUS did not improve the rate of diagnostic accuracy in unselected patients presenting to the ED with acute abdominal pain. However, as it was a safe procedure, further research should focus on patients with suspected etiologies where POCUS is particularly useful.
Trial registration: This trial was registered on ClinicalTrials.gov on 2022/07/20 (https://clinicaltrials.gov/study/NCT04912206?id=NCT04912206&rank=1) (NCT04912206).
High dietary inflammatory index associates with inflammatory proteins in plasma
Authors: Mattavelli Elisa , Piperni Elisa , Asnicar Francesco , Redaelli Laura , Grigore Liliana , Pellegatta Fabio , Nabinejad Amir , Tamburini Sabrina , Segata Nicola , Catapano Alberico Luigi , Baragetti Andrea 
Published: February 2024

Abstract
Background and aim
Unhealthy dietary habits and highly caloric foods induce metabolic alterations and promote the development of the inflammatory consequences of obesity, insulin resistance, diabetes and cardiovascular diseases. Describing an inflammatory effect of diet is difficult to pursue, owing lacks of standardized quali-quantitative dietary assessments. The Dietary Inflammatory Index (DII) has been proposed as an estimator of the pro- or anti-inflammatory effect of nutrients and higher DII values, which indicate an increased intake of nutrients with pro-inflammatory effects, relate to an increased risk of metabolic and cardiovascular diseases and we here assessed whether they reflect biologically relevant plasmatic variations of inflammatory proteins.

Methods
In this cross-sectional study, seven days dietary records from 663 subjects in primary prevention for cardiovascular diseases were analyzed to derive the intake of nutrients, foods and to calculate DII. To associate DII with the Normalized Protein eXpression (NPX), an index of abundance, of a targeted panel of 368 inflammatory biomarkers (Olink™) measured in the plasma, we divided the population by the median value of DII (1.60 (0.83–2.30)).

Results
332 subjects with estimated DII over the median value reported a higher intake of saturated fats but lower intakes of poly-unsaturated fats, including omega-3 and omega-6 fats, versus subjects with estimated dietary DII below the median value (N = 331). The NPX of 61 proteins was increased in the plasma of subjects with DII > median vs. subjects with DII < median. By contrast, in the latter group, we underscored only 3 proteins with increased NPX. Only 23, out of these 64 proteins, accurately identified subjects with DII > median (Area Under the Curve = 0.601 (0.519–0.668), p = 0.035).

Conclusion
This large-scale proteomic study supports that higher DII reflects changes in the plasmatic abundance of inflammatory proteins. Larger studies are warranted to validate.
The chronic rhinosinusitis with nasal polyp patient journey in the United States and Europe
Authors: Hwee Jeremiah , Lee Lauren , Small Mark , Smith Steven G. , Benson Victoria S. , Zhang Shiyuan 
Published: February 2024

AbstractIn this letter to the editor, we present questionnaire-based data assessing the patient journey of adults with moderate–severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the USA and five European countries. These data highlight how long and difficult the patient journey with CRSwNP can be and how improved disease awareness among physicians could lead to more timely diagnosis and treatment, and hence improved management of patients.
Metastasis of cervical cancer indicated by elevation of serum CA125 produced by mediastinal lymph nodes: a case report
Authors: Honda Ken-ichi , Miyama Masato , Nishii Yuko , Tasaka Reiko , Nakano Yusuke , Umesaki Naohiko , Fukuda Takeshi , Ichimura Tomoyuki , Yasui Tomoyo , Sumi Toshiyuki 
Published: February 2024

Abstract
Background
In patient assessment for recurrence of neoplasia, a biomarker that shows an elevated serum value before the first treatment is a candidate for follow-up examination. The biomarker squamous cell carcinoma antigen is usually utilized for follow-up of squamous cell cancer of the cervix.

Case presentation
We herein report a 30-year-old Japanese woman of postoperative metastasis of cervical squamous cell cancer to the mediastinal and supraclavicular lymph nodes as indicated by an elevated serum cancer antigen 125 concentration and not by the squamous cell carcinoma antigen value. After chemoradiotherapy and chemotherapy, the serum cancer antigen 125 concentration decreased to a normal value. Squamous cell carcinoma antigen was found to be distributed in both the squamous cell cancer tissue of the cervix and the supraclavicular lymph node metastatic tissue. By contrast, cancer antigen 125 was distributed in the supraclavicular lymph node metastatic tissue but not in the original squamous cell cancer tissue of the cervix.

Conclusion
In this case, metastasis of cervical cancer to the mediastinal and supraclavicular lymph nodes was shown by the biomarker cancer antigen 125, which was not present in the original neoplasia.
Prediction of chemical reaction yields with large-scale multi-view pre-training
Authors: Shi Runhan , Yu Gufeng , Huo Xiaohong , Yang Yang 
Published: February 2024

AbstractDeveloping machine learning models with high generalization capability for predicting chemical reaction yields is of significant interest and importance. The efficacy of such models depends heavily on the representation of chemical reactions, which has commonly been learned from SMILES or graphs of molecules using deep neural networks. However, the progression of chemical reactions is inherently determined by the molecular 3D geometric properties, which have been recently highlighted as crucial features in accurately predicting molecular properties and chemical reactions. Additionally, large-scale pre-training has been shown to be essential in enhancing the generalization capability of complex deep learning models. Based on these considerations, we propose the Reaction Multi-View Pre-training (ReaMVP) framework, which leverages self-supervised learning techniques and a two-stage pre-training strategy to predict chemical reaction yields. By incorporating multi-view learning with 3D geometric information, ReaMVP achieves state-of-the-art performance on two benchmark datasets. Notably, the experimental results indicate that ReaMVP has a significant advantage in predicting out-of-sample data, suggesting an enhanced generalization ability to predict new reactions. Scientific Contribution: This study presents the ReaMVP framework, which improves the generalization capability of machine learning models for predicting chemical reaction yields. By integrating sequential and geometric views and leveraging self-supervised learning techniques with a two-stage pre-training strategy, ReaMVP achieves state-of-the-art performance on benchmark datasets. The framework demonstrates superior predictive ability for out-of-sample data and enhances the prediction of new reactions.
Transcriptome-wide association studies associated with Crohn’s disease: challenges and perspectives
Authors: Jia Keyu , Shen Jun 
Published: February 2024

AbstractCrohn’s disease (CD) is regarded as a lifelong progressive disease affecting all segments of the intestinal tract and multiple organs. Based on genome-wide association studies (GWAS) and gene expression data, transcriptome-wide association studies (TWAS) can help identify susceptibility genes associated with pathogenesis and disease behavior. In this review, we overview seven reported TWASs of CD, summarize their study designs, and discuss the key methods and steps used in TWAS, which affect the prioritization of susceptibility genes. This article summarized the screening of tissue-specific susceptibility genes for CD, and discussed the reported potential pathological mechanisms of overlapping susceptibility genes related to CD in a certain tissue type. We observed that ileal lipid-related metabolism and colonic extracellular vesicles may be involved in the pathogenesis of CD by performing GO pathway enrichment analysis for susceptibility genes. We further pointed the low reproducibility of TWAS associated with CD and discussed the reasons for these issues, strategies for solving them. In the future, more TWAS are needed to be designed into large-scale, unified cohorts, unified analysis pipelines, and fully classified databases of expression trait loci.
Automated visual quality assessment for virtual and augmented reality based digital twins
Authors: Roullier Ben , McQuade Frank , Anjum Ashiq , Bower Craig , Liu Lu 
Published: February 2024

AbstractVirtual and augmented reality digital twins are becoming increasingly prevalent in a number of industries, though the production of digital-twin systems applications is still prohibitively expensive for many smaller organisations. A key step towards reducing the cost of digital twins lies in automating the production of 3D assets, however efforts are complicated by the lack of suitable automated methods for determining the visual quality of these assets. While visual quality assessment has been an active area of research for a number of years, few publications consider this process in the context of asset creation in digital twins. In this work, we introduce an automated decimation procedure using machine learning to assess the visual impact of decimation, a process commonly used in the production of 3D assets which has thus far been underrepresented in the visual assessment literature. Our model combines 108 geometric and perceptual metrics to determine if a 3D object has been unacceptably distorted during decimation. Our model is trained on almost 4, 000 distorted meshes, giving a significantly wider range of applicability than many models in the literature. Our results show a precision of over 97% against a set of test models, and performance tests show our model is capable of performing assessments within 2 minutes on models of up to 25, 000 polygons. Based on these results we believe our model presents both a significant advance in the field of visual quality assessment and an important step towards reducing the cost of virtual and augmented reality-based digital-twins.
Enhanced impacts of the North Pacific Victoria mode on the Indian summer monsoon onset in recent decades
Authors: Zhang Suqin , Qu Xia , Huang Gang 
Published: February 2024

AbstractVictoria mode (VM), the second dominant mode of North Pacific sea surface temperature variability, has been identified as one of the important factors influencing the Indian summer monsoon (ISM) onset. The positive phase of the May VM delays the ISM onset by both tropical and extratropical pathways. Here, we found a significant interdecadal enhancement of their relationship since the early 1990s, which is mainly attributed to the structure changes and increased variance of the VM. In recent decades, the VM has shown more significant warm SST anomalies in the tropical central Pacific, which drive the large-scale divergent circulation more effectively. This enhanced divergent circulation leads to low-level divergence and reduced rainfall in the tropical Asian summer monsoon region. The reduced rainfall excites equatorial Rossby wave response and anomalous easterly winds in the northern Indian Ocean, delaying the ISM onset. Besides, the increased variance of the VM after 1992/1993 stimulates a stronger extratropical Rossby wave train. This stationary Rossby wave train induces a stronger cooling to the northwest of India, which weakens the land-sea thermal contrast and leads to the delayed ISM onset. This finding should be taken into account to improve short-term predictions of the monsoon onset.
Engaging adolescents in chronic disease prevention research: insights from researchers about establishing and facilitating a youth advisory group
Authors: Partridge Stephanie R. , Mandoh Mariam , Todd Allyson , Raeside Rebecca 
Published: February 2024

AbstractOur comment discusses our experience establishing a youth advisory group focused on chronic disease prevention research. The comment highlights three key learnings: the need for researchers to adapt their working style, the importance of redefining the power dynamics, and disrupting traditional research structures to align with co-researcher engagement models.
Safety and efficacy of favipiravir in COVID-19 patients with pneumonia. A randomized, double-blind, placebo-controlled study (FAVID)
Authors: Horcajada Juan P. , Aldonza Rebeca , Real Mónica , Castañeda-Espinosa Silvia , Sendra Elena , Gomez-Junyent Joan , López-Montesinos Inmaculada , Gómez-Zorrilla Silvia , Briansó Silvia , Duran-Taberna Montserrat , Fernández Andrés , Tarragó Cristina , Auguet-Quintillá Teresa ,   the COVID-MAR Research group, Arenas-Miras Maria , Arrieta‐Aldea Itziar , Cañas-Ruano Esperanza , Güerri‐Fernandez Roberto , Knobel Hernando , Montero Maria Milagro , Pelegrín Ivan , Sánchez‐Martínez Francisca , Sorlí Luisa , Villar‐García Judith ,   the COVID-HJ23 group, Alibalic Ajla , Camaron Javier , Febrer Anna Maria , Bertran Laia , Barrientos Andrea 
Published: February 2024

Abstract
Purpose
To design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia.

Methods
A randomized, double blind, placebo-controlled clinical trial of favipiravir in patients with COVID-19 pneumonia was conducted in three Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was “time to clinical improvement,” measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame.

Results
Forty-four patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms.
The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment group.

Conclusions
Favipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.