bluuebunny/crossref_metadata_2025_split huggingface dataset:
The value of conventional ultrasound combined with superb microvascular imaging and color Doppler flow imaging in the diagnosis of thyroid malignant nodules: a systematic review and meta-analysis
Authors: Jiang Li , Zhang Dian , Chen Yue-Nan , Yu Xue-Juan , Pan Mei-Fang , Lian Lian 
Published: June 2023

PurposeTo evaluate and compare the value of conventional ultrasound-based superb microvascular imaging (SMI) and color Doppler flow imaging (CDFI) in the diagnosis of malignant thyroid nodule by meta-analysis.MethodsThe literature included in the Cochrane Library, PubMed, and Embase were searched by using “ superb microvascular imaging (SMI), color Doppler flow imaging (CDFI), ultrasound, thyroid nodules” as the keywords from inception through February 1, 2023. According to the inclusion and exclusion criteria, the clinical studies using SMI and CDFI to diagnose thyroid nodules were selected, and histopathology of thyroid nodules was used as reference standard. The diagnostic accuracy research quality assessment tool (QUADAS-2) was used to evaluate the quality of included literature, and the Review Manager 5.4 was used to make the quality evaluation chart. The heterogeneity test was performed on the literature that met the requirements, the combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were pooled, and a comprehensive ROC curve analysis was performed. Meta-DiSc version 1.4, StataSE 12, and Review Manager 5.4 software were used.ResultsFinally, 13 studies were included in this meta-analysis. A total of 815 thyroid malignant nodules were assessed. All thyroid nodules were histologically confirmed after SMI or CDFI. The combined sensitivity, specificity, PLR, NLR, DOR, and area under the SROC curve of SMI for the diagnosis of malignant thyroid nodules were 0.80(95%CI: 0.77-0.83), 0.79(95%CI: 0.77-0.82), 4.37(95%CI: 3.0-6.36), 0.23(95%CI: 0.15-0.35), 22.29(95%CI: 12.18-40.78), and 0.8944, respectively; the corresponding values of CDFI were 0.62(95%CI: 0.57-0.67), 0.81(95%CI: 0.78-0.85), 3.33(95%CI: 2.18-5.07), 0.41(95%CI: 0.27-0.64), 8.93(95%CI: 3.96-20.16), and 0.8498. Deek funnel pattern showed no significant publication bias.ConclusionThe diagnostic efficiency of SMI for malignant thyroid nodules is better than CDFI, and SMI technology can provide significantly more information on vascularity, make up for the deficiency of CDFI, and has better clinical application value.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023402064.
Behavioral and neuropsychiatric challenges across the lifespan in individuals with Rubinstein-Taybi syndrome
Authors: Qu’d Dima , Schmitt Lauren M. , Leston Amber , Harris Jacqueline R. , Slavotinek Anne , Riddle Ilka , Brightman Diana S. , Simpson Brittany N. 
Published: June 2023

Introduction: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder characterized by developmental and intellectual disability, broadening of thumbs and halluces, and characteristic facial features. Pathogenic variants in CREBBP lead to RSTS type 1 (RSTS1) and in EP300 lead to RSTS type 2 (RSTS2). Individuals with RSTS can demonstrate a variety of behavioral and neuropsychiatric challenges, including anxiety, hyperactivity/inattention, self-injury, repetitive behaviors, and aggression. Behavioral challenges are consistently reported as one of the primary factors impacting quality of life. Despite the high prevalence and morbidity of behavioral and neuropsychiatric features of RSTS, a paucity of data exists regarding its natural history.Methods: To better understand the neurocognitive and behavioral challenges faced by individuals with RSTS, 71 caregivers of individuals with RSTS, ranging in age from one to 61 years, completed four questionnaires measuring obsessive compulsive disorder (OCD)-like symptoms, anxiety, challenging behaviors, and adaptive behavior and living skills.Results: Results revealed a high prevalence of neuropsychiatric and behavioral challenges across ages. We found specific challenging behaviors were worse in school age individuals. Scaled adaptive behavior and living skill scores differed across ages with an increased gap between typically developing peers becoming more apparent at older ages. Between types, individuals with RSTS2 had better adaptive behavior and living skills and less stereotypic behaviors but higher social phobia than individuals with RSTS1. Further, female individuals with RSTS1 appear to have increased hyperactivity. However, both groups had impairments in adaptive functioning compared to typically developing peers.Discussion: Our findings support and expand previous reports of a high prevalence of neuropsychiatric and behavioral challenges in individuals with RSTS. However, we are the first to report differences between types of RSTS. Further, age-related differences were seen with higher challenging behaviors within school-age individuals, which may improve over time, and lower adaptive behavioral skills compared to normative scales. Anticipation of these potential differential challenges across age is vital for proactive management for individuals with RSTS. Our study underscores the importance of enacting neuropsychiatric and behavioral screening earlier in childhood so appropriate management can be implemented. However, further longitudinal studies in larger cohorts are needed to understand better how behavioral and neuropsychiatric characteristics of RSTS evolve over the lifespan and differentially affect subpopulation groups.
Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders
Authors: Lee Evan M. , Verma Megha , Palaniappan Nila , Pope Emiko M. , Lee Sammie , Blacher Lindsey , Neerumalla Pooja , An William , Campbell Toko , Brown Cris , Hurst Stacy , Marshall Bess , Hershey Tamara , Nunes Virginia , López de Heredia Miguel , Urano Fumihiko 
Published: June 2023

Objective: Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity and prognosis of Wolfram syndrome more accurately.Approach: Patient data from the Washington University International Registry and Clinical Study for Wolfram Syndrome and patient case reports were analyzed to select for patients with two recessive mutations in the WFS1 gene. Mutations were classified as being either nonsense/frameshift variants or missense/in-frame insertion/deletion variants. Missense/in-frame variants were further classified as transmembrane or non-transmembrane based on whether they affected amino acid residues predicted to be in transmembrane domains of WFS1. Statistical analysis was performed using Wilcoxon rank-sum tests with multiple test adjustment applied via the Bonferonni correction.Results: A greater number of genotype variants correlated with earlier onset and a more severe presentation of Wolfram syndrome. Secondly, non-sense and frameshift variants had more severe phenotypic presentations than missense variants, as evidenced by diabetes mellitus and optic atrophy emerging significantly earlier in patients with two nonsense/frameshift variants compared with zero or one nonsense/frameshift variants. In addition, the number of transmembrane in-frame variants demonstrated a statistically significant dose-effect on age of onset of diabetes mellitus and optic atrophy among patients with either one or two in-frame variants.Summary/Conclusion: The results contribute to our current understanding of the genotype-phenotype relationship of Wolfram syndrome, suggesting that alterations in coding sequences result in significant changes in the presentation and severity of Wolfram. The impact of these findings is significant, as the results will aid clinicians in predicting more accurate prognoses and pave the way for personalized treatments for Wolfram syndrome.
MK2 drives progression of pancreas and colon cancers by suppressing CD8+ T cell cytotoxic function and is a potential immunotherapy target
Authors: Jacenik Damian , Lebish Eric J. , Beswick Ellen J. 
Published: June 2023

BackgroundImmune cell composition is a critical and dynamic component of the tumor microenvironment, which has an impact on immunosuppression and progression of cancer. T cells, especially CD8+ T cells, are one of the major immune cell types responsible for tumor cell killing employing receptor-ligand mediated apoptosis and/or releasing lytic granules among others. Accumulating evidence highlighted that adoptive transfer of activated and/or modified immune cells can enhance anti-tumorigenic immune responses and serve as promising therapy approach for patients with cancers. The mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a serine/threonine protein kinase, which controls production and secretion of numerous pro-inflammatory cytokines and chemokines involved in tumorigenesis. However, limited efforts have been made to learn how MK2 may affects CD8+ T cell action and function in the tumor microenvironment especially in gastrointestinal cancers.MethodsTo explore the therapeutic potential of MK2 in the immune response mediated by CD8+ T cells, RAG1 knockout mice with PK5L1940 and BRAF cells-derived allograft tumors were treated with WT or MK2 knockout CD8+ T cells. The phenotype of CD8+ T cells with MK2 depletion were evaluated in vitro. Immunofluorescence staining, real-time PCR and multiplex analysis were utilized to estimate the expression of apoptotic and lytic factors.ResultsHere, we show that CD8+ T cells with MK2 depletion prevent gastrointestinal cancer growth, which is accompanied by enhanced expression and secretion of factors related to apoptosis. Moreover, using in vitro and in vivo approaches, we found that depletion of MK2 lead to hyperactivation of CD8+ T cells and enhanced anti-tumor immunity.ConclusionOverall, we documented that MK2 drives the progression of gastrointestinal cancers and prevents immune response generated by CD8+ T cells suggesting potential implications of MK2 in the immunotherapy of gastrointestinal cancers.
Effects of fucoidan on growth performance, immunity, antioxidant ability, digestive enzyme activity, and hepatic morphology in juvenile common carp (Cyprinus carpio)
Authors: Li Fang , Sun Hanchang , Li Yang , He Die , Ren Chaoying , Zhu Chengke , Lv Guangjun 
Published: June 2023

Fucoidan with its excellent biological activities such as growth promotion, antioxidant and strong immunity, is widely used in animal production. The present study was conducted to investigate the influences of feeding fucoidan on growth performance, biochemical indices, immunity, the antibacterial ability of plasma, the digestive enzyme activity of the intestine, antioxidant capacity, and the histological structure of liver in juvenile common carp. Five experimental diets added with 0 (Diet 1), 500 (Diet 2), 1,000 (Diet 3), 1,500 (Diet 4), and 2,000 (Diet 5) mg/kg fucoidan were fed to triplicate groups of 30 fish (35.83 ± 0.24 g) respectively for 8 weeks. The results showed that fish fed diets with a fucoidan supplementation of 1,666.67–1,757 mg/kg might have the best growth performance (p&lt; 0.05). The levels of plasma total protein (TP) and albumin (ALB) in Diet 3, Diet 4, and Diet 5 were higher than those in Diet 1 and Diet 2 (p&lt; 0.05). Moreover, the contents of plasma C3, LYZ, and IgM; the antibacterial ability of serum; and the activity of SOD, CAT, POD, and GPX in the liver, and ACP, AKP, LPS, AMS, and TRY in the intestine significantly improved; the contents of LPO and MDA in the liver were notably decreased in diets with fucoidan supplement (p&lt; 0.05). Furthermore, the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the contents of total bilirubin (TB) and glucose (Glu) in Diet 5 were the highest among the groups. Meanwhile, proinflammatory factors (plasma IL-6 and IL-1β) had a higher expression, but anti-inflammatory factors (plasma IL-1) had a lower expression in Diet 5 (p &gt; 0.05). It indicated that a higher dose (2,000 mg/kg) of fucoidan may induce inflammation and metabolic disorders. Interestingly, histological results of liver also indicated that dietary fucoidan intake in certain amounts (500–1,500 mg/kg) could ameliorate hepatic morphology, but the high dosage (2,000 mg/kg) probably damaged the liver. To the best of our knowledge, this is the first study on the application of fucoidan as a functional additive to juvenile common carp. The results of the present study can be used to guide the application of fucoidan in healthy aquaculture and can further reveal the effect and mechanism of fucoidan on the nutritional physiology of aquatic animals.
Clinical observation and mechanism of acupuncture on amnestic mild cognitive impairment based on the gut-brain axis: study protocol for a randomized controlled trial
Authors: Bao Qiongnan , Liu Yiwei , Zhang Xinyue , Li Yaqin , Wang Ziqi , Ye Fang , He Xia , Xia Manze , Chen Zhenghong , Yao Jin , Zhong Wanqi , Wu Kexin , Wang Ziwen , Sun Mingsheng , Chen Jiao , Hong Xiaojuan , Zhao Ling , Yin Zihan , Liang Fanrong 
Published: June 2023

BackgroundAmnestic mild cognitive impairment (aMCI) is a pre-dementia condition associated with declined cognitive function dominated by memory impairment. The occurrence of aMCI is associated with the gut-brain axis. Previous studies have shown cognitive improvements in MCI after acupuncture treatment. This study evaluates whether acupuncture can produce a therapeutic effect in patients with aMCI by modulating the gut-brain axis.Methods and designThis is a prospective, parallel, multicenter randomized controlled trial. A total of 40 patients with aMCI will be randomly assigned to an acupuncture group (AG) or a waiting-list group (WG), participants in both groups will receive health education on improving cognitive function at each visit, and acupuncture will be conducted twice a week for 12 weeks in the AG. Another 20 matched healthy volunteers will be enrolled as normal control. The primary outcome will be the change in Alzheimer’s Disease Assessment Scale-cognitive scale score before and after treatment. Additionally, functional magnetic resonance imaging data, faeces, and blood will be collected from each participant to characterize the brain function, gut microbiota, and inflammatory cytokines, respectively. The differences between patients with aMCI and healthy participants, and the changes in the AG and WG groups before and after treatment will be observed. Ultimately, the correlation among brain function, gut microbiota, inflammatory cytokines, and clinical efficacy evaluation in patients with aMCI will be analyzed.DiscussionThis study will identify the efficacy and provide preliminary data on the possible mechanism of acupuncture in treating aMCI. Furthermore, it will also identify biomarkers of the gut microbiota, inflammatory cytokines, and brain function correlated with therapeutic effects. The results of this study will be published in peer-reviewed journals.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2200062084.
Association of changes in obesity and abdominal obesity status with early-onset colorectal cancer risk: a nationwide population-based cohort study
Authors: Song Ji Hyun , Seo Ji Yeon , Jin Eun Hyo , Chung Goh Eun , Kim Young Sun , Bae Jung Ho , Kim Sunmie , Han Kyung-Do , Yang Sun Young 
Published: June 2023

Background and aimsThe incidence of early-onset colorectal cancer (EO-CRC, diagnosed before 50 years of age) has increased in recent decades. The aim of this study was to investigate the association between changes in obesity status and EO-CRC risk.MethodsFrom a nationwide population-based cohort, individuals &lt;50 years old who participated in the national health checkup program in both 2009 and 2011 were included. Obesity was defined as a body mass index ≥25 kg/m2. Abdominal obesity was defined as a waist circumference ≥ 90 cm in men and ≥ 85 cm in women. Participants were classified into 4 groups according to the change in obesity (normal/normal, normal/obese, obese/normal, persistent obese) and abdominal obesity (normal/normal, normal/abdominal obesity, abdominal obesity/normal, persistent abdominal obesity) status. Participants were followed up until 2019 and censored when they became 50 years old.ResultsAmong 3,340,635 participants, 7,492 patients were diagnosed with EO-CRC during 7.1 years of follow-up. The risk of EO-CRC was higher in the persistent obesity and persistent abdominal obesity groups than in the normal/normal groups (hazard ratio (HR) [95% confidence interval (CI)] = 1.09 [1.03–1.16] and 1.18 [1.09–1.29], respectively). Participants with both persistent obesity and abdominal obesity had a higher EO-CRC risk than those in the normal/normal groups for both [HR (95% CI) = 1.19 (1.09–1.30)].ConclusionPersistent obesity and persistent abdominal obesity before the age of 50 are associated with a slightly increased risk of EO-CRC. Addressing obesity and abdominal obesity in young individuals might be beneficial in reducing the risk of EO-CRC.
SAELGMDA: Identifying human microbe–disease associations based on sparse autoencoder and LightGBM
Authors: Wang Feixiang , Yang Huandong , Wu Yan , Peng Lihong , Li Xiaoling 
Published: June 2023

IntroductionIdentification of complex associations between diseases and microbes is important to understand the pathogenesis of diseases and design therapeutic strategies. Biomedical experiment-based Microbe-Disease Association (MDA) detection methods are expensive, time-consuming, and laborious.MethodsHere, we developed a computational method called SAELGMDA for potential MDA prediction. First, microbe similarity and disease similarity are computed by integrating their functional similarity and Gaussian interaction profile kernel similarity. Second, one microbe-disease pair is presented as a feature vector by combining the microbe and disease similarity matrices. Next, the obtained feature vectors are mapped to a low-dimensional space based on a Sparse AutoEncoder. Finally, unknown microbe-disease pairs are classified based on Light Gradient boosting machine.ResultsThe proposed SAELGMDA method was compared with four state-of-the-art MDA methods (MNNMDA, GATMDA, NTSHMDA, and LRLSHMDA) under five-fold cross validations on diseases, microbes, and microbe-disease pairs on the HMDAD and Disbiome databases. The results show that SAELGMDA computed the best accuracy, Matthews correlation coefficient, AUC, and AUPR under the majority of conditions, outperforming the other four MDA prediction models. In particular, SAELGMDA obtained the best AUCs of 0.8358 and 0.9301 under cross validation on diseases, 0.9838 and 0.9293 under cross validation on microbes, and 0.9857 and 0.9358 under cross validation on microbe-disease pairs on the HMDAD and Disbiome databases. Colorectal cancer, inflammatory bowel disease, and lung cancer are diseases that severely threat human health. We used the proposed SAELGMDA method to find possible microbes for the three diseases. The results demonstrate that there are potential associations between Clostridium coccoides and colorectal cancer and one between Sphingomonadaceae and inflammatory bowel disease. In addition, Veillonella may associate with autism. The inferred MDAs need further validation.ConclusionWe anticipate that the proposed SAELGMDA method contributes to the identification of new MDAs.
Alzheimer's early detection in post-acute COVID-19 syndrome: a systematic review and expert consensus on preclinical assessments
Authors: Vandersteen Clair , Plonka Alexandra , Manera Valeria , Sawchuk Kim , Lafontaine Constance , Galery Kevin , Rouaud Olivier , Bengaied Nouha , Launay Cyrille , Guérin Olivier , Robert Philippe , Allali Gilles , Beauchet Olivier , Gros Auriane 
Published: June 2023

IntroductionThe risk of developing Alzheimer's disease (AD) in older adults increasingly is being discussed in the literature on Post-Acute COVID-19 Syndrome (PACS). Remote digital Assessments for Preclinical AD (RAPAs) are becoming more important in screening for early AD, and should always be available for PACS patients, especially for patients at risk of AD. This systematic review examines the potential for using RAPA to identify impairments in PACS patients, scrutinizes the supporting evidence, and describes the recommendations of experts regarding their use.MethodsWe conducted a thorough search using the PubMed and Embase databases. Systematic reviews (with or without meta-analysis), narrative reviews, and observational studies that assessed patients with PACS on specific RAPAs were included. The RAPAs that were identified looked for impairments in olfactory, eye-tracking, graphical, speech and language, central auditory, or spatial navigation abilities. The recommendations' final grades were determined by evaluating the strength of the evidence and by having a consensus discussion about the results of the Delphi rounds among an international Delphi consensus panel called IMPACT, sponsored by the French National Research Agency. The consensus panel included 11 international experts from France, Switzerland, and Canada.ResultsBased on the available evidence, olfaction is the most long-lasting impairment found in PACS patients. However, while olfaction is the most prevalent impairment, expert consensus statements recommend that AD olfactory screening should not be used on patients with a history of PACS at this point in time. Experts recommend that olfactory screenings can only be recommended once those under study have reported full recovery. This is particularly important for the deployment of the olfactory identification subdimension. The expert assessment that more long-term studies are needed after a period of full recovery, suggests that this consensus statement requires an update in a few years.ConclusionBased on available evidence, olfaction could be long-lasting in PACS patients. However, according to expert consensus statements, AD olfactory screening is not recommended for patients with a history of PACS until complete recovery has been confirmed in the literature, particularly for the identification sub-dimension. This consensus statement may require an update in a few years.