Structural Abnormalities Research Articles

Prenatal alcohol exposure and associations with physical size, dysmorphology and neurodevelopment: a systematic review and meta-analysis

BackgroundFetal alcohol spectrum disorder (FASD) is a significant public health concern, yet there is no internationally agreed set of diagnostic criteria or summary of underlying evidence to inform diagnostic decision-making. This systematic review assesses associations of prenatal alcohol exposure (PAE) and outcomes of diagnostic assessments, providing an evidence base for the improvement of FASD diagnostic criteria.MethodsSix databases were searched (inception–February 2023). Case-controls or cohort studies examining associations between participants with/without PAE or a FASD diagnosis and the domains of physical size, dysmorphology, functional neurodevelopment and/or brain structure/neurology were included. Excluded studies were non-empirical, sample size < 10, PAE determined via biological markers only, or no suitable comparison group. Summary data were extracted and associations between outcomes and standardised levels of PAE or FASD diagnosis determined using random-effects meta-analyses. Certainty of the evidence was assessed using GRADE.ResultsOf the 306 included studies, 106 reported physical size, 43 dysmorphology, 195 functional neurodevelopment and 110 structural/neurological outcomes, with 292 different outcomes examined. There was a dose–response relationship between PAE and head circumference, as well as measures of physical size, particularly at birth. There was also an association between higher PAE levels and characteristic sentinel facial dysmorphology, as well as many of the current functional neurodevelopmental outcomes considered during diagnosis. However, data were often lacking across the full range of exposures. There was a lack of evidence from studies examining PAE to support inclusion of non-sentinel dysmorphic features, social cognition, speech-sound impairments, neurological conditions, seizures, sensory processing or structural brain abnormalities (via clinical MRI) in diagnostic criteria. GRADE ratings ranged from very low to moderate certainty of evidence.ConclusionsThis comprehensive review provides guidance on which components are most useful to consider in the diagnostic criteria for FASD. It also highlights numerous gaps in the available evidence. Future well-designed pregnancy cohort studies should specifically focus on dose–response relationships between PAE and dysmorphology, neurodevelopment and brain structure/neurological outcomes.Systematic review registrationPROSPERO: CRD42021230522.

Systemic treatments for radioiodine-refractory thyroid cancers.

Differentiated thyroid cancers (DTCs) constitute the primary histological subtype within thyroid cancer. Due to DTCs' distinctive radioiodine (RAI) uptake mechanism, standard treatment involving surgery, with or without adjunctive therapy using RAI and levothyroxine inhibition, typically yields favorable prognoses for the majority of patients with DTCs. However, this favorable outcome does not extend to individuals with decreased RAI uptake, termed radioiodine-refractory thyroid cancers (RAI-RTCs). Recent research has revealed that the genetic mutations and gene rearrangements affecting sites such as RTKs, RAS, BRAF and TERTp lead to structural and functional abnormalities in encoded proteins. These abnormalities aberrantly activate signaling pathways like the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-hydroxykinase (PI3K) signaling pathways, resulting in thyroid cells dedifferentiation, sodium/iodide symporter (NIS) dysfunction, and consequent the RAI-refractory nature of DTCs. Targeted therapy tailored to mutations presents a promising avenue for the treatment of RAI-RTCs. Lenvatinib and sorafenib, multi-kinase inhibitors, represent the standard first-line systemic treatment options, while cabozantinib is the standard second-line treatment option, for this purpose. Furthermore, ongoing clinical trials are exploring selective kinase inhibitors, immune checkpoint inhibitors, and combination therapies. Notably, numerous clinical trials have demonstrated that selective kinase inhibitors like BRAF, MEK and mTOR inhibitors can restore RAI uptake in tumor cells. However, further validation through multicenter, large-sample, double-blinded randomized controlled trials are essential. Enhanced treatment strategies and innovative therapies are expected to benefit a broader spectrum of patients as these advancements progress.

Hippocampal contributions to biologic, behavioral and cognitive deficits in autism: An update review

The most characteristic symptoms for the diagnosis of autism spectrum disorder (ASD) and the future life of the individual are deterioration in social communication and stereotyped or repetitive behaviors. ASD is associated with diverse atypical difficulties, including memory, learning, language, emotion, and cognitive impairment. Consequently, the hippocampus is important for memory, learning, language ability, emotional regulation, and cognitive mapping. Thus, the hippocampus plays an influential role in the pathophysiological mechanisms of ASD. Here, we provide an updated review of hippocampal structural and functional abnormalities and highlight the hippocampus as an important area for future research.

Intermittent Fasting Ameliorates Age-Induced Morphological Changes in Aged Albino Rat Kidney via Autophagy Activation and Reduction of Apoptosis and Inflammation

Abstract Aging is a biological process with gradual decrease of cell function. Kidneys are one of the organs with higher susceptibility to the development of age-dependent tissue damage. Intermittent fasting has several beneficial effects on age-related degenerative changes. The aim of this study was to investigate the possible beneficial effect of intermittent fasting in delaying age-related renal changes and the possible mechanisms of this effect. Thirty male albino rats were classified into three groups: control, adult rats aged 3 months; aged group, 15-month-old rats and maintained until the age of 18 months; and intermittent fasting-aged groups, 15-month-old rats maintained on intermittent fasting for 3 months. Kidneys were processed for histological and immunohistochemical study. Aging resulted in a significant reduction in renal function and significant several degenerative changes in renal corpuscles and tubules which showed abnormal histological structure with increased collagen deposition. Aging caused significant reduction in the expression of autophagic marker light chain 3 with increased expression of active caspase-3 and inducible nitric oxide synthase. Intermittent fasting significantly improved these age-related renal changes. Intermittent fasting effectively prevents age-related renal changes through the reduction of age-related oxidative stress, inflammation, apoptosis, and activation of autophagy.

Cytokines Measured in Nasal Lavage Compared to Induced Sputum in Patients with Mild Cystic Fibrosis

The measurement of cytokines in induced sputum and nasal lavage (NL) samples has been performed for years in people with cystic fibrosis (CF). The aim of this study was to directly compare sputum and NL samples and interpret results based on disease severity in patients who were categorized as having mild or severe lung disease. The categorization was based primarily on structural abnormalities detected on lung computed tomography and secondarily on lung function. The serum inflammatory markers neutrophil elastase (NE), IL-1β, 2, 6, 8, 10 and 17a were measured in each sputum and NL sample. Thirty-two sample pairs from 29 patients were included in this study (13 mild, 19 severe). In the patients classified as severe, many systemic inflammatory markers as well as sputum cytokines were significantly higher compared to those in the mild patients. However, all the markers measured in the NL were higher in the mild patients (p =&lt; 0.05 for NE, IL-6 and IL-8). In addition, many cytokines in the NL correlated negatively with those in the sputum samples. Major differences in the cytokine levels were shown although the samples were obtained at the same time in the same patient. Advanced structural lung disease was closely related to systemic and lower airway inflammation, whereas preserved lung function was associated with higher levels in the NL. We hypothesize that the main part of the immune response takes place in the nasal mucosa in patients with minor pulmonary changes. Our results suggest that inflammation must be interpreted individually depending on the compartment in which it is measured. Further research is needed to accurately understand inflammatory markers measured in NL.

A review on achromatopsia: Exploring genetic basis, diagnostic innovations, and therapeutic prospects

Achromatopsia (ACHM) is a rare inherited retinal disorder characterized by partial or complete color blindness, which impacts individuals' quality of life and daily functioning. This review delves into the genetic basis, diagnostic innovations, and therapeutic prospects associated with ACHM. The main objective is to comprehensively explore the current understanding of ACHM, including genetic mutations, diagnostic techniques, and management approaches, while also discussing potential therapeutic interventions. Achromatopsia primarily results from mutations in genes encoding cone photoreceptor proteins, such as GNAT2, ATF6, PDE6H, PDE6C, CNGA3, and CNGB3. Various diagnostic methods, including electroretinography (ERG) and optical coherence tomography (OCT), are pivotal in confirming ACHM diagnosis by assessing cone function and structural abnormalities in dysfunctional cone cells. This review also highlights gene therapy interventions aimed at restoring cone function, highlighting promising advancements in preclinical and clinical settings. Additionally, it discusses the clinical features of ACHM, such as reduced visual acuity, photophobia, and color vision impairment, emphasizing the need for tailored management strategies to increase patients' quality of life. This review underscores the complex genetic landscape of ACHM and the importance of accurate diagnosis through advanced diagnostic modalities such as ERG and OCT. While there is currently no cure for ACHM, management approaches focus on symptom alleviation and improving patients' daily functioning. Gene therapy has emerged as a promising avenue for potential treatment, with ongoing research aiming to address the underlying genetic defects and restore cone photoreceptor function. The findings of this review hold clinical relevance by providing insights into the pathogenesis, diagnosis, and management of ACHM, guiding healthcare professionals in delivering personalized care to affected individuals. Continued research and advancements in gene therapy offer hope for future therapeutic interventions, highlighting the importance of updating the latest developments in the field of ACHM.

The biogeography of the mucosa-associated microbiome in health and disease.

Little is known about the biogeography of the mucosa associated microbiome (MAM) in patients with inflammatory bowel disease (IBD) versus controls in different segments of the gastrointestinal tract, as well as the links between the MAM, gastrointestinal symptoms, and use of proton pump inhibitors (PPI). We recruited 59 controls (without structural abnormalities and gastrointestinal symptoms), 44 patients with ulcerative colitis (UC) and 31 with Crohn's disease (CD). Biopsies from various segments of the upper and lower gastrointestinal tract were collected. Microbial composition was assessed via 16S rRNA gene amplicon analysis and the bacterial load of the mucosal biopsies were assessed via qPCR. The MAM was examined in the context of disease status, PPI usage, the severity of gastrointestinal symptoms, and the symptom response to a standardised nutrient challenge (SNC). Microbial communities of the MAM in the upper and lower gastrointestinal tract differed. IBD patients were characterised by relative and absolute depletion of numerous genera known to produce butyrate and/or propionate, with the largest differentiation being the depletion of Faecalibacterium in the lower gastrointestinal tract of CD patients. Notably, PPI users exhibited an enrichment of Faecalibacterium in the lower gastrointestinal tract. The severity of gastrointestinal symptoms, as well as the symptom response to the SNC, were significantly associated with MAM composition in the gastrointestinal tract. The absolute and relative composition of the MAM is variable across different segments of the gastrointestinal tract. These quantitative changes indicates that MAM can be targeted in specific segments of the GI tract to improve patient outcomes.

Efficacy and Safety of Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by structural and functional abnormalities. Current management strategies, such as medications and septal reduction therapies, have significant limitations and risks. Recently, cardiac myosin inhibitors (CMIs) like mavacamten and aficamten have shown promise as noninvasive treatment options. This meta-analysis aims to evaluate the efficacy and safety of CMIs in HCM patients. PubMed/MEDLINE, Embase, the Cochrane Library, Ovid, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared CMIs to control treatments in HCM patients from inception till June 15, 2024. A random-effects model was used to pool odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes along with the corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the χ2 test and Higgins I 2 statistic, and sensitivity and subgroup analyses were performed. Six RCTs involving 826 patients were included. CMI therapy significantly reduced resting left ventricular outflow tract (LVOT) gradient (MD, −37.64; 95% CI, −46.71 to −28.56), Valsalva LVOT gradient (MD, −46.04; 95% CI, −57.60 to −34.48), post-exercise LVOT peak gradient (MD, −48.64; 95% CI, −68.20 to −28.88), N-terminal pro-b-type natriuretic peptide levels (MD, −1.05; 95% CI, −1.64 to −0.47), and cardiac troponin I levels (MD, −7.96; 95% CI, −12.84 to −3.07). Improvements were observed in peak oxygen consumption (MD, 1.20; 95% CI, 0.23–2.17) and patient-reported outcomes (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score: MD, 6.44; 95% CI, 3.50–9.37), with more patients achieving New York Heart Association class improvement &gt;1 (OR, 4.05; 95% CI, 2.61–6.30). Treatment-emergent adverse events were higher with CMI therapy (OR, 1.45; 95% CI, 1.02–2.05), but serious adverse events and other safety outcomes were comparable in both groups. CMIs, including mavacamten and aficamten, significantly improve clinical outcomes in HCM patients with a manageable safety profile. These results indicate that CMIs offer a promising noninvasive alternative to septal reduction therapies.

Association of concussion history with psychiatric symptoms, limbic system structure, and kynurenine pathway metabolites in healthy, collegiate-aged athletes

Psychiatric outcomes are commonly observed in individuals with repeated concussions, though their underlying mechanism is unknown. One potential mechanism linking concussion with psychiatric symptoms is inflammation-induced activation of the kynurenine pathway, which is thought to play a role in the pathogenesis of mood disorders. Here, we investigated the association of prior concussion with multiple psychiatric-related outcomes in otherwise healthy male and female collegiate-aged athletes (N = 212) with varying histories of concussion recruited from the community. Specially, we tested the hypotheses that concussion history is associated with worse psychiatric symptoms, limbic system structural abnormalities (hippocampal volume, white matter microstructure assessed using neurite orientation dispersion and density imaging; NODDI), and elevations in kynurenine pathway (KP) metabolites (e.g., Quinolinic acid; QuinA). Given known sex-effects on concussion risk and recovery, psychiatric outcomes, and the kynurenine pathway, the moderating effect of sex was considered for all analyses. More concussions were associated with greater depression, anxiety, and anhedonia symptoms in female athletes (ps ≤ 0.005) and greater depression symptoms in male athletes (p = 0.011). More concussions were associated with smaller bilateral hippocampal tail (ps < 0.010) and left hippocampal body (p < 0.001) volumes across male and female athletes. Prior concussion was also associated with elevations in the orientation dispersion index (ODI) and lower intracellular volume fraction in several white matter tracts including the in uncinate fasciculus, cingulum-gyrus, and forceps major and minor, with evidence of female-specific associations in select regions. Regarding serum KP metabolites, more concussions were associated with elevated QuinA in females and lower tryptophan in males (ps ≤ 0.010). Finally, serum levels of QuinA were associated with elevated ODI (male and female athletes) and worse anxiety symptoms (females only), while higher ODI in female athletes and smaller hippocampal volumes in male athletes were associated with more severe anxiety and depression symptoms (ps ≤ 0.05). These data suggest that cumulative concussion is associated with psychiatric symptoms and limbic system structure in healthy athletes, with increased susceptibility to these effects in female athletes. Moreover, the associations of outcomes with serum KP metabolites highlight the KP as one potential molecular pathway underlying these observations.

Technologies for prenatal diagnosis

The possibility of examining the foetus during the first months of gestation in order to diagnose any structural abnormalities is a recent acquisition in modern obstetrics. This has been made possible by the introduction of the use of ultrasound for diagnostic purposes, and the refinement of the technique of taking amniotic fluid (amniocentesis).

Resistance physical exercise modulates metabolic adipokines, decreases body weight, and improves glomerular filtration in patients with chronic kidney disease in hemodialysis.

Chronic kidney disease (CKD) is a condition characterized by abnormalities in kidney structure and function that persist for more than 3months. It is estimated that more than 800 million people in the world have a diagnosis of CKD. To remove the harmful metabolic substances from the body, people with CKD need to perform hemodialysis. Due to their beneficial effects against a wide range of clinical conditions, physical exercise is considered a non-pharmacological therapy. This study aimed to evaluate the beneficial effects of resistance exercise during hemodialysis on metabolic adipokines, myokines, body weight, and glomerular filtration rate in patients living with CKD. Briefly, the blood samples were collected in two moments: immediately before the start of the resistance exercise protocol and 1week after the end of the protocol. Resistance exercise protocol was performed thrice a week for 12weeks and applied during hemodialysis sessions. Here, resistance exercise increases the circulating irisin (14.56%; p = 0.0112), handgrip strength (5.70%; p = 0.0036), glomerular filtration rate (25.9%; p = 0.022) and significantly decreases adiponectin (- 55.7%; p = 0.0044), body weight (- 3.7%; p = 0.0001), glucose (- 22%; p = 0.009), and albumin levels (- 9.55%; p = 0.0001). Conversely, leptin levels (- 10.9%; p = 0.38), iron (3.05%; p = 0.705), ferritin (3.24%; p = 0.880), hemoglobin (- 0.52%; p = 0.75), total cholesterol (7.9%; p = 0.19), LDL (- 9.99%; p = 0.15) and HDL (- 4.8%; p = 0.45), did not change after resistance exercise. Interestingly, 1,25 hydroxyvitamin D levels were significantly increased (14.5%; p = 0.01) following resistance exercise. Considering the effect of sex (males vs. females), we found that irisin levels increased in females but not in males after the resistance exercise protocol. Furthermore, handgrip strength and body weight were different, indicating that males had the highest strength and weight. We demonstrated that both males and females had lower albumin levels after the resistance exercise protocol. In conclusion, we suggest that resistance exercise has beneficial effects in the CKD population by modulating adipokines and metabolic myokines and therefore can be used as a non-pharmacological adjunctive therapy in CKD patients undergoing HD.

Gray matter and cognitive alteration related to chronic obstructive pulmonary disease patients: combining ALE meta-analysis and MACM analysis.

Chronic obstructive pulmonary disease (COPD) is frequently comorbid with cognitive impairment, but it has not been paid enough attention, and its neuroanatomical characteristics have not been fully identified. Voxel-based morphometric (VBM) studies comparing gray matter (GM) abnormalities in COPD patients with healthy controls (HCs) were searched using 8 electronic databases from the inception to March 2023. Stereotactic data were extracted and tested for convergence and differences using the activation likelihood estimation (ALE) method. Moreover, based on the ALE results, a structural meta-analytic connectivity modeling (MACM) was conducted to explore the co-atrophy pattern in patients with COPD. Last, behavioral analysis was performed to assess the functional roles of the regions affected by COPD. In total, 11 studies on COPD with 949 participants were included. Voxel-based meta-analysis revealed significant GM abnormalities in the right postcentral gyrus (including inferior parietal lobule), left precentral gyrus, and left cingulate gyrus (including paracentral lobule) in patients with COPD compared with HCs. Further MACM analysis revealed a deeper co-atrophy pattern between the brain regions with abnormal GM structure and the insula in COPD patients. Behavioral analysis showed that the abnormal GM structure in the left cingulate gyrus (including paracentral lobule) was strongly associated with cognitive function, especially executive function. COPD comorbid with cognitive impairment has a specific neurostructural basis of GM structural abnormalities, which may also involve a deeper co-atrophy pattern between the insula. These findings enhance our understanding of the underlying neuropathogenesis and suggest potential imaging markers for cognitive impairment in COPD patients. PROSPERO registration number: CRD42022298722.

Bovine aortic arch: a potential indicator that may not serve in prenatal diagnosis - a study based on fetal anatomy, genetics, and postnatal clinical outcomes

ObjectiveTo investigate the structural abnormalities, genetic results, and postnatal clinical outcomes of fetuses with bovine aortic arch (Bovine Aortic Arch, BAA) to provide a basis for prenatal counseling and management.MethodsA retrospective analysis was conducted on 216 fetuses diagnosed with bovine aortic arch through prenatal ultrasound screening at the First Affiliated Hospital of Anhui Medical University and the No.901 Hospital of the Joint Service of the People’s Liberation Army from January 2019 to February 2023. Their family history of genetic diseases, prenatal screening results, and postnatal follow-up data were collected. The fetuses were divided into an isolated BAA group (n = 192) and a non-isolated BAA group (n = 24). Chromosomal karyotyping and copy number variation (CNV) testing were conducted, and statistical analysis was performed using SPSS 22.0 software.ResultsOf the 216 fetuses with BAA, 192 were isolated BAA (88.89%), and 24 were non-isolated BAA (11.11%). Among the isolated BAA fetuses, only 1 case (0.52%) had chromosomal karyotype and pathogenic CNV abnormalities. Among the non-isolated BAA fetuses, 4 cases (16.67%) had chromosomal or CNV abnormalities, but the overall risk was low. The postnatal outcomes of isolated BAA fetuses were good (99.48%), while 79.17% of non-isolated BAA fetuses had good postnatal outcomes.ConclusionMost BAA fetuses are isolated, with a very low incidence of chromosomal abnormalities and pathogenic CNVs, and have good postnatal outcomes. The clinical value of isolated BAA is limited, and invasive prenatal diagnosis is not recommended for low-risk populations. Prenatal screening should focus on the risk of concurrent severe structural anomalies and chromosomal abnormalities.

The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies.

Background: Osteoarthritis (OA) is the most common degenerative joint disease and affects millions of people worldwide, particularly the elderly population. The pathophysiology of OA is complex and involves multiple factors. Methods: Several studies have emphasized the crucial role of inflammation in this process. The receptor activator of NF-κB ligand (RANKL), the receptor activator of NF-κB (RANK), and osteoprotegerin (OPG) trigger a signaling cascade that leads to the excessive production of RANKL in the serum. Conclusions: The aim of this narrative review is (i) to assess the role of the RANK/RANKL/OPG signaling pathway in the context of OA progression, focusing especially on the physiopathology and on all the mechanisms leading to the activation of the inflammatory cascade, and (ii) to evaluate all the potential therapeutic strategies currently available that restore balance to bone formation and resorption, reducing structural abnormalities and relieving pain in patients with OA.

Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells.

From their early genesis, tumour cells integrate with the surrounding normal cells to form an abnormal structure that is tightly integrated with the host organism via blood and lymphatic vessels and even neural associations. Using these connections, emerging cancers send a plethora of mediators that efficiently perturb the entire organism and induce changes in distant tissues. These perturbations serendipitously favour early metastatic establishment by promoting a more favourable tissue environment (niche) that supports the persistence of disseminated tumour cells within a foreign tissue. Because the establishment of early metastatic niches represents a key limiting step for metastasis, the creation of a more suitable pre-conditioned tissue strongly enhances metastatic success. In this Review, we provide an updated view of the mechanisms and mediators of primary tumours described so far that induce a pro-metastatic conditioning of distant organs, which favours early metastatic niche formation. We reflect on the nature of cancer-induced systemic conditioning, considering that non-cancer-dependent perturbations of tissue homeostasis are also able to trigger pro-metastatic conditioning. We argue that a more holistic view of the processes catalysing metastatic progression is needed to identify preventive or therapeutic opportunities.

Structural and functional whole brain changes in autism spectrum disorder at different age stages.

Autism spectrum disorder (ASD) is a developmental disorder involving regional changes and local neural disturbances. However, few studies have investigated the dysfunctional phenomenon across different age stages. This study explores the structural and functional brain changes across different developmental stages in individuals with ASD, focusing on childhood (6-12 years), adolescence (12-18 years), and adulthood (18 + years). Using a comprehensive set of neuroimaging metrics, including modulated and non-modulated voxel-based morphometry (VBM), regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF), we identified significant stage-specific alterations in both VBM and functional measurements. Our results reveal that ASD is associated with progressive and stage-specific abnormalities in brain structure and function, with distinct patterns emerging at each developmental stage. Specifically, we observed significant modulated VBM reductions in the precuneus, lentiform nucleus, and inferior parietal lobule, accompanied by increases in the midbrain and sub-gyral regions. Moreover, we observed unmodulated VBM increment in regions including lentiform nucleus and thalamus. Functionally, ReHo analyses demonstrated disrupted local synchronization in the medial frontal gyrus, while ALFF and fALFF metrics highlighted altered spontaneous brain activity in the sub-gyral and sub-lobar. Finally, correlation analyses revealed that stage-specific findings are closely linked to clinical social- and behavior-related scores, with VBM in the inferior parietal lobule and putamen as well as ReHo in supplemental motor area being significantly associated with restrictive repetitive behaviors in childhood. These findings underscore the importance of considering age-specific brain changes when studying ASD and suggest that targeted interventions may be necessary at different developmental stages.

Emerging Role of Natriuretic Peptides in Diabetes Care: A Brief Review of Pertinent Recent Literature

Diabetes markedly increases susceptibility to adverse cardiovascular events, including heart failure (HF), leading to heightened morbidity and mortality rates. Elevated levels of natriuretic peptides (NPs), notably B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP), correlate with cardiac structural and functional abnormalities, aiding in risk stratification and treatment strategies in individuals with diabetes. This article reviews the intricate relationship between diabetes and HF, emphasizing the role of NPs in risk assessment and guiding therapeutic strategies, particularly in individuals with type 2 diabetes mellitus (T2DM). We also explore the analytical and clinical considerations in the use of natriuretic peptide testing and the challenges and prospects of natriuretic-peptide-guided therapy in managing cardiovascular risk in patients with diabetes. We conclude with some reflections on future prospects for NPs.

CLPr_in_ML: Cleft Lip and Palate Reconstructed Features with Machine Learning

Background: Cleft lip and palate are two of the most common craniofacial congenital malformations in humans. It influences tens of millions of patients worldwide. The hazards of this disease are multifaceted, extending beyond the obvious facial malformation to encompass physiological functions, oral health, psychological well-being, and social aspects. Objective: The primary objective of our study is to demonstrate the importance of imaging in detecting cleft lip and palate. By observing the morphological and structural abnormalities involving the lip and palate through imaging methods, this study aims to establish imaging as the primary diagnostic approach for this disease. Methods: In this work, we proposed a novel model to analyze unilateral complete cleft lip and palate after velopharyngeal closure and non-left lip and palate patients from the Department of Stomatology of Xuzhou First People's Hospital, Conical Beam CT (CBCT) images in silicon. In order to demonstrate the generalization, the simulated dataset was constructed using the random disturbance factor, which is from the actual dataset. We extracted several raw features from CBCT images in detail. Then, we proposed a novel feature reconstruction method, including six types of reconstructed factors, to reconstruct the existing features. Then, the reconstructed features weretrained with machine learning algorithms. Finally, the testing and independent data model was utilized to analyze the performance of this work. Results: By comparing different operator features, the min operator, max operator, average operator, and all operators can achieve good performances in both the testing set and the independent set. result: none Conclusion: With the different operator features, the majority of classification models, including Gradient Boosting, Hist Gradient Boosting, Multilayer Perceptron, lightGBM, and broadened learning, classification algorithms can get the well-performances in the selected reconstructed feature operators.

A Novel Homozygous Variant in CPLANE1 Gene in a Patient with Developmental Deficits

Background: Oral-facial-digital syndrome (OFDS) type 6 is a rare subtype of Joubert syndrome characterized by orofacial anomalies and polydactyly with neurological features of Joubert syndrome. This rare syndrome is divided into thirteen subtypes, all of which demonstrate autosomal recessive inheritance, except for OFDS type 1 which demonstrates X-linked dominant inheritance. Case Presentation: A 19-year-old man with mild developmental delay was brought to a rural community clinic, as he had become irritable and angry, in the recent past. There was no history of prior medical conditions. In view of orofacial anomalies, and developmental deficits, a genetic analysis was requested. Karyotype analysis revealed a normal male karyotype (46,XY) in all 30 metaphase spreads analyzed. No numerical or structural chromosomal abnormalities were observed. Clinical exome sequencing and chromosomal microarray detected a variant of uncertain significance in exon 5 of CPLANE1 gene c.365T&amp;gt;G (p.Val122Gly) leading to substitution of Glycine for Valine. This was confirmed by Sanger sequencing. Parents were heterozygous, and the unaffected sibling was homozygous for the wild-type allele. This variant has not been reported earlier in the mutation databases or gnomAD. Runs of homozygosity (ROH) analysis showed a 3.2 Mb ROH around the CPLANE1 gene in the proband, which was absent in both parents and the unaffected sibling. Conclusion: We find a novel homozygous mutation in the CPLANE1 gene in a patient of non-consanguineous parentage with atypical orofacial features. This suggests that potentially deleterious, rare variants may occur in the heterozygous state in the population. Hence, sequencing of population samples might help understand the genetic epidemiology of rare syndromes.

Global Knowledge Map and Emerging Research Trends in Induced Pluripotent Stem Cells and Hereditary Diseases: A CiteSpace-based Visualization and Analysis.

The rise of induced pluripotent stem cells (iPSCs) technology has ushered in a landmark shift in the study of hereditary diseases. However, there is a scarcity of reports that offer a comprehensive and objective overview of the current state of research at the intersection of iPSCs and hereditary diseases. Therefore, this study endeavors to categorize and synthesize the publications in this field over the past decade through bibliometric methods and visual knowledge mapping, aiming to visually analyze their research focus and clinical trends. The English language literature on iPSCs and hereditary diseases, published from 2014 to 2023 in the Web of Science Core Collection (WoSCC), was examined. The CiteSpace (version 6.3.R1) software was utilized to visualize and analyze country/region, institution, scholar, co-cited authors, and co-cited journals. Additionally, the co-occurrence, clustering, and bursting of co-cited references were displayed. Analysis of 347 articles that met the inclusion criteria revealed a steady increase in the number of published articles and citation frequency in the field over the past decade. With regard to the countries/regions, institutions, scholars, and journals where the articles were published, the highest numbers were found in the USA, the University of California System, Suren M. Zakian, and Stem Cell Research, respectively. The current research is focused on the construction of disease models, both before and after correction, as well as drug target testing for single-gene hereditary diseases. Chromosome transplantation genomic therapy for hereditary diseases with abnormal chromosome structures may emerge as a future research hotspot in this field.