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Abstract Background To assess the efficacy of artificial intelligence (AI) models in diagnosing and prognosticating acute appendicitis (AA) in adult patients compared to traditional methods. AA is a common cause of emergency department visits and abdominal surgeries. It is typically diagnosed through clinical assessments, laboratory tests, and imaging studies. However, traditional diagnostic methods can be time-consuming and inaccurate. Machine learning models have shown promise in improving diagnostic accuracy and predicting outcomes. Main body A systematic review following the PRISMA guidelines was conducted, searching PubMed, Embase, Scopus, and Web of Science databases. Studies were evaluated for risk of bias using the Prediction Model Risk of Bias Assessment Tool. Data points extracted included model type, input features, validation strategies, and key performance metrics. Results In total, 29 studies were analyzed, out of which 21 focused on diagnosis, seven on prognosis, and one on both. Artificial neural networks (ANNs) were the most commonly employed algorithm for diagnosis. Both ANN and logistic regression were also widely used for categorizing types of AA. ANNs showed high performance in most cases, with accuracy rates often exceeding 80% and AUC values peaking at 0.985. The models also demonstrated promising results in predicting postoperative outcomes such as sepsis risk and ICU admission. Risk of bias was identified in a majority of studies, with selection bias and lack of internal validation being the most common issues. Conclusion AI algorithms demonstrate significant promise in diagnosing and prognosticating AA, often surpassing traditional methods and clinical scores such as the Alvarado scoring system in terms of speed and accuracy.

Abstract Background Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder associated with a wide range of clinical symptoms. Some researchers have used cluster analysis (CA), a group of non-supervised learning methods that identifies homogenous clusters within different entities based on their similarity. Objective and methods This literature review aims to identify published articles that apply CA to IBS patients. We searched relevant keywords in PubMed, Embase, Web of Science, and Scopus. We reviewed studies in terms of the selected variables, participants’ characteristics, data collection, methodology, number of clusters, clusters’ profiles, and results. Results Among the 14 articles focused on the heterogeneity of IBS, eight of them utilized K-means Cluster Analysis (K-means CA), four employed Hierarchical Cluster Analysis, and only two studies utilized Latent Class Analysis. Seven studies focused on clinical symptoms, while four articles examined anocolorectal functions. Two studies were centered around immunological findings, and only one study explored microbial composition. The number of clusters obtained ranged from two to seven, showing variation across the studies. Males exhibited lower symptom severity and fewer psychological findings. The association between symptom severity and rectal perception suggests that altered rectal perception serves as a biological indicator of IBS. Ultra-slow waves observed in IBS patients are linked to increased activity of the anal sphincter, higher anal pressure, dystonia, and dyschezia. Conclusion IBS has different subgroups based on different factors. Most IBS patients have low clinical severity, good QoL, high rectal sensitivity, delayed left colon transit time, increased systemic cytokines, and changes in microbial composition, including increased Firmicutes-associated taxa and depleted Bacteroidetes-related taxa. However, the number of clusters is inconsistent across studies due to the methodological heterogeneity. CA, a valuable non-supervised learning method, is sensitive to hyperparameters like the number of clusters and random initialization of cluster centers. The random nature of these parameters leads to diverse outcomes even with the same algorithm. This has implications for future research and practical applications, necessitating further studies to improve our understanding of IBS and develop personalized treatments.

The burden of metabolic disorders is alarmingly increasing globally. On the other hand, sustainability is the key project of the 21st century. Natural products offer a coherent option for the complementary management of both these challenges. Ficus carica (FC), commonly known as the fig fruit, has an experimentally proven potency for the modulation of cell cycle, immunity, inflammation, metabolism, and oxidative stress. Here, we review the potential of FC-derived products (FCDP) in slowing down the progression of cancers, acute/chronic inflammation-related conditions, infections, metabolic disorders, toxicities, neurological and neuromuscular diseases, gastrointestinal disorders, vascular diseases, and skin-stressing conditions, as well as, in boosting normal healthy functions of the endocrine, immune, metabolic, and nervous systems. It reveals a variety of cellular and molecular targets for FCDP: cytokines (TNF-α, IL-1β, IL-6, IL-10, IL-12, IL-18, IFN-γ), chemokines (CCL2), other inflammatory mediators (CRP, PGE2), immune receptors (TLR-2, TLR-4, FcεRI), oxidative stress-related markers (SOD, GSH, MDA, GPx, catalase, ROS, NO, protein carbonyls), kinases (MAPKs, hexokinase, G6Pase, FBPase, PEPCK, Akt, AMPK, GSK3, CDKs), other enzymes (COX-2, iNOS, MMPs, caspases), growth factors/receptors (VEGF, EGFR), hormones (DHEAS, prolactin, GnRH, FSH, LH, estradiol, DHT, insulin), cell death-related markers (Bcl-2, Bax, Bak, FasL, gasdermins, cytochrome C), glucose transporter protein (Glut4), and transcription factors (NF-κB, HNF-4α, Foxo, PGC-1α, PPAR-γ, C/EBP-α, CREB, NFATC1, STAT3). FCDP cause both activation and inhibition of AMPK, MAPK, and NF-κB signaling to confer condition-specific advantages. Such a broad-range activity might be attributed to different mechanisms of action of FCDP in modulating functions within the classical immunometabolic system, but also beyond.

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

Loneliness has been associated with different health outcomes in the following domains: general health, well-being, physical health, mental health, sleep, and cognitive function. However, the most significant associations fall into mental health- and well-being-related outcomes. Moreover, loneliness is an identified risk factor for all-cause mortality. This article overviews the systematic and meta-analytic studies, which have investigated epidemiology and etiology, associated medical and neuropsychiatric conditions, and interventions for loneliness. Meta-analyses have associated higher levels/prevalence of loneliness with pathological conditions, including physical (cardiovascular diseases, obesity, and cancer) and mental health conditions (dementia, cognitive impairment, depression, anxiety, suicide, substance abuse, frailty, and addiction). Furthermore, loneliness commonly occurs to people during particular physiological conditions, for example, childhood, adulthood, elderly, pregnancy, and taking care of others. Moreover, young adults commonly experience transient loneliness. For all these pathological/physiological conditions, COVID-19 has been confirmed as a loneliness-worsening condition. Genetic background, in addition to environmental factors, plays a role in the etiology of loneliness. Biomarkers mainly include neural correlates, including aberrations in the structure/function of cognitive or emotional control-related brain regions, inflammatory correlates, and anthropometric measures. The current interventions for loneliness alleviation are mostly focused on older people, for whom the evidence derived from systematic or meta-analytic studies shows none-to-moderate benefits and substantial heterogeneity across studies. The evidence is not adequate to conclude about the effectiveness of interventions in youth. In addition to the need for pathology- and population-specific interventions for loneliness reduction/prevention, there is a need to survey loneliness longitudinally to examine the causality of loneliness-health associations.

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophic factor expressed in several tissues, including the brain, gut, and pancreas. Activation of the BDNF/TrkB/CREB reduces hepatic gluconeogenesis, induces hepatic insulin signal transduction, and protects against pancreatic beta-cell loss in diabetes mellitus (DM). Several studies have investigated the possible association between BDNF and DM and its complications, but the results have been conflicting.AimIn the present study, we aimed at systematically reviewing the literature on the serum and plasma levels of BDNF in DM and its subgroups such as T2DM, DM patients with depression, and patients with retinopathy.MethodsA comprehensive search was conducted in PubMed, Scopus, and Web of Science. We identified 28 eligible studies and calculated the standardized mean difference (SMD) of outcomes as an effect measure.ResultsThe meta-analysis included 2734 patients with DM and 6004 controls. Serum BDNF levels were significantly lower in patients with DM vs. controls (SMD = -1.00, PConclusionsSerum BDNF levels were lower in patients with DM, T2DM, DM with depression, and DM and DR than the controls. Our findings are in line with the hypothesis that decreased BDNF levels might impair glucose metabolism and contribute to the pathogenesis of DM and its complications.

Background Cancers are among the most common causes of mortality and morbidity. Recently, bispecific antibodies (BsAbs) have been used for cancer treatment. The aim of this systematic review and meta-analysis will be to determine the safety and efficacy of BsAbs in the treatment of solid tumors. Methods We will search five electronic databases, PubMed, EMBASE, Scopus, Web of Science, and CENTRAL, in addition to Clinical-Trials.gov and metaRegister of controlled trials and backward and forward citation searching of included studies. Eligible studies will be controlled clinical trials evaluating safety and/or efficacy of BsAbs in adult patients with solid tumors. The primary outcomes will be the incidence of safety and efficacy measures. Title and/or abstract screening, full text reviewing, data collection, and quality assessment will be done by two reviewers. We will use The Cochrane Collaboration’s risk of bias tool 2 (RoB2) to assess the quality of included studies. If I-square heterogeneity was greater than 40%, we will implement random effect model. Subgroup analysis and meta-regression will be undertaken if applicable. The metaprop command of STATA will be used to calculate frequency of AEs. Funnel plot, Egger’s and Peter’s tests will be utilized to evaluate publication bias in case of including at least ten studies. We will use sensitivity analysis to evaluate the effects of funding sources and continuity correction on effects size. Conclusions The findings of the present study will provide information on safety and efficacy of BsAbs for physicians and researchers in the management of solid tumors. Trial registration Registration on PROSPERO CRD42021227879 Also, important protocol amendments will be stated on PROSPERO registration.

BackgroundChanges in endothelial function are implicated in the spread of tuberculosis (TB). Studies suggest a role for the vascular endothelial growth factor (VEGF) in TB-related endothelial function changes. However, the findings of studies investigating the VGEF profile in TB are not consistent, and no formal systematic review and meta-analysis exists summarizing these studies.MethodsWe did a meta-analysis of studies assessing VEGF levels in patients with TB. A systematic search on June 25, 2021, was conducted for eligible studies that made VEGF measurements in an unstimulated sample, e.g., a blood fraction (plasma or serum), cerebrospinal fluid (CSF), pleural effusion (PE), or bronchoalveolar lavage fluid, and ascites or pericardial fluid for patients with TB and controls without TB. Also, studies that made simultaneous measurements of VEGF in blood and PE or CSF in the same patients with TB were included. Longitudinal studies that provided these data at baseline or compared pre-post anti-tuberculosis treatment (ATT) levels of VEGF were included. The primary outcome was the standardized mean difference (SMD) of VEGF levels between the comparison groups.Results52 studies were included in the meta-analysis. There were 1787 patients with TB and 3352 control subjects of eight categories: 107 patients with transudative pleural effusion, 228 patients with congestive heart failure (CHF)/chronic renal failure (CRF), 261 patients with empyema and parapneumonic effusion (PPE), 241 patients with cirrhosis, 694 healthy controls (with latent TB infection or uninfected individuals), 20 patients with inactive tuberculous meningitis (TBM), 123 patients with non-TBM, and 1678 patients with malignancy. The main findings are as follows: (1) serum levels of VEGF are higher in patients with active TB compared with healthy controls without other respiratory diseases, including those with latent TB infection or uninfected individuals; (2) both serum and pleural levels of VEGF are increased in patients with TPE compared with patients with transudative, CHF/CRF, or cirrhotic pleural effusion; (3) ascitic/pericardial fluid, serum, and pleural levels of VEGF are decreased in patients with TB compared with patients with malignancy; (4) pleural levels of VEGF are lower in patients with TPE compared with those with empyema and PPE, whereas serum levels of VEGF are not different between these patients; (5) both CSF and serum levels of VEGF are increased in patients with active TBM compared with controls, including patients with inactive TBM or non-TBM subjects; (6) post-ATT levels of VEGF are increased compared with pre-ATT levels of VEGF; and (7) the mean age and male percentage of the TB group explained large and total amount of heterogeneity for the meta-analysis of blood and pleural VEGF levels compared with healthy controls and patients with PPE, respectively, whereas these moderators did not show any significant interaction with the effect size for other analyses.DiscussionThe important limitation of the study is that we could not address the high heterogeneity among studies. There might be unmeasured factors behind this heterogeneity that need to be explored in future research. Meta-analysis findings align with the hypothesis that TB may be associated with abnormal vascular function, and both local and systemic levels of VEGF can be used to trace this abnormality.

Abstract Background Amyotrophic lateral sclerosis (ALS) is a highly progressive and debilitating neurodegenerative disease, which usually leads to the death of affected individuals within a few years after the onset of symptoms. ALS is currently incurable and very little is known about its pathophysiology. Finding validated biomarkers will help us to advance our understanding of ALS etiology and find better strategies for early diagnosis and management of the disease. The main aim of the present systematic review is to evaluate the concentration of 11 frequently reported biomarkers for ALS in peripheral blood and CSF of patients diagnosed with ALS compared with controls. Methods This systematic review protocol has been established according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 guideline. We will include all types of observational studies with human subjects that investigated the concentrations of intended biomarkers (amyloid beta (Aβ-42), tau and phosphorylated tau (p-Tau), neurofilaments, S100β, cystatin C, progranulin (PGRN), glial fibrillary acidic protein (GFAP), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), TAR DNA-binding protein-43 (TDP43), YKL-40, and CHIT1 in CSF or peripheral blood of ALS patients for initial assessment. Also, we will include case series with a minimum of 10 cases and clinical trials which have measured baseline biomarker levels. Case studies, case reports, reviews, letters, and animal and in vitro studies will be excluded. Multiple electronic databases including Cochrane Library, MEDLINE (PubMed), ISI Web of Science, and EMBASE will be searched to find all eligible articles published since 1980. No language restriction will be applied. All titles and abstracts retrieved by searching information sources will be evaluated independently by two authors against the eligibility criteria. The following information will be extracted from each included study by two independent authors: bibliographic details (first author, study title, year of publication, country), demographics and clinical information (number of patients and controls, type of ALS and controls, study design, age, gender, specimen, biomarkers levels, ALS functional rating scale Revised (ALSFRS-R), duration of disease), and measurements (method, value type, biomarkers levels). We will use the extracted mean and standard deviation (SD) of biomarkers concentrations to calculate the standardized mean difference (SMD) and 95% confidence intervals (CI). The primary outcome measures are the mean difference of biomarker levels between ALS patients and controls, different types of ALS, and ALS patients with genetic mutations. Discussion We will systematically review the literature and analyze studies of biomarker level in CSF and peripheral blood of patients with ALS and controls. The results will help us to identify biomarkers with possible diagnostic and prognostic value. Systematic review registration PROSPERO CRD42017078127

BackgroundBrain-derived neurotrophic factor (BDNF) plays a crucial role in the survival, differentiation, growth, and plasticity of the central nervous system (CNS). Post-traumatic stress disorder (PTSD) is a complex syndrome that affects CNS function. Evidence indicates that changes in peripheral levels of BDNF may interfere with stress. However, the results are mixed. This study investigates whether blood levels of BDNF in patients with post-traumatic stress disorder (PTSD) are different.MethodsWe conducted a systematic search in the major electronic medical databases from inception through September 2019 and identified Observational studies that measured serum levels of BDNF in patients with PTSD compared to controls without PTSD.Results20 studies were eligible to be included in the present meta-analysis. Subjects with PTSD (n = 909) showed lower BDNF levels compared to Non-PTSD controls (n = 1679) (SMD = 0.52; 95% confidence interval: 0.18 to 0.85). Subgroup meta-analyses confirmed higher levels of BDNF in patients with PTSD compared to non-PTSD controls in plasma, not serum, and in studies that used sandwich ELISA, not ELISA, for BDNF measurement. Meta-regressions showed no significant effect of age, gender, NOS, and sample size.ConclusionsPTSD patients had increased serum BDNF levels compared to healthy controls. Our finding of higher BDNF levels in patients with PTSD supports the notion that PTSD is a neuroplastic disorder.

BACKGROUND:TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to contribute to the various intracellular signals and immune responses, importantly the regulation of Th1 and Th17 cell differentiation, which plays a remarked role in fight against inflammatory and autoimmune diseases. Association of TIM family gene polymorphisms with rheumatoid arthritis (RA) has been frequently investigated. The findings however are not entirely consistent. Therefore, we carried out the present meta-analysis to examine the association between RA and the following TIM family gene polymorphisms: rs41297579, rs1036199, rs10515746, and rs7700944. METHODS:A systematic search of Scopus, PubMed, and Web of Science databases was conducted through December 2018. Combined odds ratios (OR) with their corresponding 95% confidence intervals (CI) were calculated under different possible genetic models. RESULTS:A total of eight case-control studies were included in the present meta-analysis. The results demonstrated significant association of RA with TIM-3 rs1036199 polymorphism under dominant (OR, 1.93, 95% CI, 1.43-2.61) and allelic models (OR, 1.74, 95% CI, 1.31-2.30). None of the other examined polymorphisms indicated significant association with RA. CONCLUSIONS:The present meta-analysis revealed that the TIM-3 rs1036199 polymorphism might confer susceptibility to RA. Further studies are required to reassert our findings.

The ATP8A2 protein is mainly located in the brain and takes part in the lipid flipping process. Mutations in the ATP8A2 gene and chromosomal translocations that interfere with the ATP8A2 gene product have been reported in association with global developmental delay and hypotonia. Here, we will report a three-year-old male presented with major phenotypic features of dysequilibrium syndrome (DES), including severe hypotonia, global developmental delay, speech problem, and strabismus. Whole exome sequencing revealed a homozygous in-frame deletion in the ATP8A2 gene (c.1286_1288delAGA, p.Lys429del). This ATP8A2 variant has not been reported yet and seems to be linked to the phenotypic features of dysequilibrium syndrome.

Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (p

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Friedreich’s ataxia (FRDA) is a rare autosomal recessive spinocerebellar ataxia which in the majority of cases is associated with a GAA-trinucleotide repeat expansion in the first intron of Frataxin gene located on chromosome 9. The clinical features include progressive gait and limb ataxia, cerebellar dysarthria, neuropathy, optic atrophy, and loss of vibration and proprioception. Ataxia with ocular motor apraxia type 1 (AOA1) is another autosomal recessive cerebellar ataxia which is associated with oculomotor apraxia, hypoalbuminaemia, and hypercholesterolemia. Here we describe two siblings (13- and 10-year-old) display overlapping clinical features of both early-onset FRDA and AOA1. Almost all of laboratory test (including urinary analysis/culture, biochemistry, peripheral blood smear, C-reactive protein level, erythrocyte sedimentation rate-1h) results were within the normal range for both patients. Due to the normal laboratory test results; we concluded that the diagnosis was more likely to be FRDA than AOA1. Therefore, neurologists should bear in mind that clinical presentations of FRDA may vary widely from the classical phenotype of gait and limb ataxia to atypical manifestations such as oculomotor apraxia.

Different metabolic profiles as well as comorbidities are common in people with Down Syndrome (DS). Therefore it is relevant to know whether micronutrient levels in people with DS are also different. This systematic review was designed to review the literature on micronutrient levels in people with DS compared to age and sex-matched controls without DS. We identified sixty nine studies from January 1967 to April 2016 through main electronic medical databases PubMed, Scopus, and Web of knowledge. We carried out meta-analysis of the data on four essential trace elements (Cu, Fe, Se, and Zn), six minerals (Ca, Cl, K, Mg, Na, and P), and five vitamins (vitamin A, B9, B12, D, and E). People with DS showed lower blood levels of Ca (standard mean difference (SMD) = -0.63; 95% confidence interval (CI): -1.16 to -0.09), Se (SMD = -0.99; 95% CI: -1.55 to -0.43), and Zn (SMD = -1.30; 95% CI: -1.75 to -0.84), while red cell levels of Zn (SMD = 1.88; 95% CI: 0.48 to 3.28) and Cu (SMD = 2.77; 95% CI: 1.96 to 3.57) were higher. They had also higher salivary levels of Ca (SMD = 0.85; 95% CI: 0.38 to 1.33) and Na (SMD = 1.04; 95% CI: 0.39 to 1.69). Our findings that micronutrient levels are different in people with DS raise the question whether these differences are related to the different metabolic profiles, the common comorbidities or merely reflect DS.