Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrodiagnostic, Sonographic, and Clinical Features of Carpal Tunnel Syndrome with Bifid Median Nerve

Purpose A bifid median nerve (BMN) is not a rare variant. This study aimed to investigate the features of carpal tunnel syndrome (CTS) accompanied by BMN. Patients and Methods In this retrospective study, we defined a BMN group as CTS with BMN and a non-bifid median nerve (NMN) group as CTS without BMN. All hands were assigned to four severity grades according to the findings of electrodiagnosis (EDx): very mild, mild, moderate, and severe. The cross-sectional area (CSA) of the median nerve, palmar bowing of the flexor retinaculum, and persistent median artery (PMA) were assessed by ultrasonography. Numerical pain rating scale (NRS) and symptom duration were assessed as clinical variables. Results Sixty-four hands (57 patients) and 442 hands (341 patients) were enrolled in the BMN and the NMN groups, respectively. BMN was prevalent in 12.6% of all CTS hands. The distribution of EDx severity grade was milder in the BMN group than in the NMN group (P<0.001). The CSA of the BMN group was 16.2±4.1 mm2, slightly larger than 15.1±4.2 mm2 in the NMN group (P=0.056). The BMN group showed higher NRS than the NMN group (5.5±1.5 and 4.4±1.7, respectively; P<0.001). In the subgroup analysis, NRS was significantly higher in the BMN group than in the NMN group at all EDx severity grades. In the BMN group, the PMA group showed greater EDx severity (P=0.037) and higher NRS (6.0 and 5.0, respectively; P=0.012) than the non-PMA group. The radial side branch’s CSA was larger than that of the ulnar side branch (10.0 mm2 and 6.0 mm2, respectively; P<0.001). Conclusion CTS with BMN presented more severe symptoms and relatively milder EDx severity. When assessing the severity of CTS with BMN, the clinical symptoms should primarily be considered, as well as we should complementarily evaluate the EDx and ultrasonography.
Targeting KRAS in Solid Tumors: Current Challenges and Future Opportunities of Novel KRAS Inhibitors

Activating mutations in RAS family proteins are found in ~25% of all human cancers. Different solid tumors are correlated with mutations in certain isoforms of RAS, with Kirsten RAS (KRAS) being the most frequently mutated isoform. Historically, KRAS has been acknowledged as “undruggable”, largely because the RAS proteins do not appear to present suitable pockets to which small inhibitory molecules can bind. However, this scenario has changed over the last years with the advent of novel KRAS inhibitors. In this review, we describe the role of KRAS mutation across different solid tumors, providing data on novel KRAS inhibitors currently under development and an updated overview of ongoing research in this field. A literature search was performed to select papers, abstracts, and oral presentation on KRAS inhibitory strategies in KRAS mutated solid tumors. Overall, the most promising therapeutic results have been obtained with molecules targeting KRAS G12C, thus paving the way for a significant therapeutic improvement in non-small cell lung cancer. Unfortunately, KRAS G12C mutation is rather uncommon in other solid tumors, namely pancreatic ductal adenocarcinoma and colorectal cancer. Several combination strategies are currently under evaluation in clinical trials, in order to bypass the resistance mechanisms responsible for the intrinsic resistance of mutated KRAS to the main therapeutic strategies adopted to date. Results suggest that the therapeutic scenario of KRAS has started to change, and further research will bring therapeutic results in this field.
Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug

Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands.
Functional Health Literacy in Patients with Cardiovascular Diseases: Cross-Sectional Study in Ethiopia

Objective This study assessed functional health literacy and associated factors among adult patients with cardiovascular diseases (CVDs) in Ethiopia. Methods A cross-sectional study was conducted on 410 respondents from May 1 to July 1, 2020, using a functional health literacy questionnaire consisting of 14 items that covers three conceptually distinct functional health literacy domains: having sufficient information to manage my health, ability to find good health information and understand health information well enough to know what to do. Data were analyzed using the Statistical Package for Social Sciences (SPSS) Version 23. Data were collected by exit face-to-face interview using an interviewer administered and pre-tested questionnaire. Statistical significance of associated variables had been declared based on the adjusted odds ratio (AOR) with its 95% CI and p-value <0.05. Results Adequate functional health literacy was determined in 55.4% of CVD patients understanding health information whereas inadequate functional health literacy was determined in 53.9% participants for finding health information and in 50.5% of them having sufficient information to manage my health. Educational status was found to have a statistically significant association across the three domains. Conclusion The functional health literacy level of CVD patients varied by domain. Educational status of the participant is significantly associated with the three domains of functional health literacy whereas household monthly income and number of information sources are significantly associated with having sufficient information and the ability to find good health information. The findings indicate the need to streamline medical communication that improves the functional health literacy of CVD patients.
The Cause of Hereditary Hearing Loss in GJB2 Heterozygotes—A Comprehensive Study of the GJB2/DFNB1 Region

Hearing loss is a genetically heterogeneous sensory defect, and the frequent causes are biallelic pathogenic variants in the GJB2 gene. However, patients carrying only one heterozygous pathogenic (monoallelic) GJB2 variant represent a long-lasting diagnostic problem. Interestingly, previous results showed that individuals with a heterozygous pathogenic GJB2 variant are two times more prevalent among those with hearing loss compared to normal-hearing individuals. This excess among patients led us to hypothesize that there could be another pathogenic variant in the GJB2 region/DFNB1 locus. A hitherto undiscovered variant could, in part, explain the cause of hearing loss in patients and would mean reclassifying them as patients with GJB2 biallelic pathogenic variants. In order to detect an unknown causal variant, we examined 28 patients using NGS with probes that continuously cover the 0.4 Mb in the DFNB1 region. An additional 49 patients were examined by WES to uncover only carriers. We did not reveal a second pathogenic variant in the DFNB1 region. However, in 19% of the WES-examined patients, the cause of hearing loss was found to be in genes other than the GJB2. We present evidence to show that a substantial number of patients are carriers of the GJB2 pathogenic variant, albeit only by chance.
L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678. 1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446. 1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.
COL12A1 Single Nucleotide Polymorphisms rs240736 and rs970547 Are Not Associated with Temporomandibular Joint Disc Displacement without Reduction

Temporomandibular disorders (TMDs) may affect up to 25% of the population, with almost 70% of these TMD cases developing malpositioning of the disc over time in what is known as internal derangement (ID). Despite significant efforts, the molecular mechanism underlying disease progression is not yet very well known. In this study, the role of COL12A1 rs970547 and rs240736 polymorphisms as potential genetic factors regulating ID was investigated. The study included 124 Caucasian patients of both sexes after disc displacement without reduction (DDwoR) in either one or two temporomandibular joints (TMJs), either of which meet the criteria for this condition. All patients underwent clinical examination and 3D digital imaging. The COL12A1 rs970547 and rs240736 polymorphisms were evaluated. There were no statistically significant differences in the chi-square test between the study group and healthy controls. The examined COL12A1 rs240736 and rs970547 polymorphisms do not contribute to DDwoR in Polish Caucasians.
Use of Grape Peels By-Product for Wheat Pasta Manufacturing

Grape peels (GP) use in pasta formulation represents an economic and eco-friendly way to create value-added products with multiple nutritional benefits. This study aimed to evaluate the effect of the GP by-product on common wheat flour (Triticum aestivum), dough and pasta properties in order to achieve the optimal level that can be incorporated. Response surface methodology (RSM) was performed taking into account the influence of GP level on flour viscosity, dough cohesiveness and complex modulus, pasta color, fracturability, chewiness, cooking loss, total polyphenols, dietary fibers and resistant starch amounts. The result show that 4.62% GP can be added to wheat flour to obtain higher total polyphenols, resistant starch and dietary fiber contents with minimum negative effects on pasta quality. Flour viscosity, dough cohesiveness, complex modulus and pasta fracturability of the optimal sample were higher compared to the control, while chewiness was lower. Proteins’ secondary structures were influenced by GP addition, while starch was not affected. Smooth starch grains embedded in a compact protein structure containing GP fiber was observed. These results show that GP can be successfully incorporated in wheat pasta, offering nutritional benefits by their antioxidants and fiber contents, without many negative effects on the final product’s properties.
Meet the Insidious Players: Review of Viral Infections in Head and Neck Cancer Etiology with an Update on Clinical Trials

Head and neck cancers (HNC) occur in the upper aerodigestive tract and are among the most common cancers. The etiology of HNC is complex, involving many factors, including excessive tobacco and alcohol consumption; over the last two decades, oncogenic viruses have also been recognized as an important cause of HNC. Major etiological agents of nasopharynx carcinoma and oropharyngeal carcinoma include Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), both of which are able to interfere with cell cycle control. Additionally, the association of hepatitis C and hepatitis B infection was observed in oral cavity, oropharyngeal, laryngeal, and nasopharyngeal cancers. Overall prognoses depend on anatomic site, stage, and viral status. Current treatment options, including radiotherapy, chemotherapy, targeted therapies and immunotherapies, are distributed in order to improve overall patient prognosis and survival rates. However, the interplay between viral genome sequences and the health, disease, geography, and ethnicity of the host are crucial for understanding the role of viruses and for development of potential personalized treatment and prevention strategies. This review provides the most comprehensive analysis to date of a vast field, including HNC risk factors, as well as viral mechanisms of infection and their role in HNC development. Additionally, currently available treatment options investigated through clinical practice are emphasized in the paper.
Association of rs11780592 Polymorphism in the Human Soluble Epoxide Hydrolase Gene (EPHX2) with Oxidized LDL and Mortality in Patients with Diabetic Chronic Kidney Disease

Soluble epoxide hydrolase 2 (EPHX2) is an enzyme promoting increased cellular apoptosis through induction of oxidative stress (OS) and inflammation. The EPHX2 gene which encodes soluble EPHX2 might be implicated in the pathogenesis and development of OS and atherosclerosis. We aimed to assess the possible association between two functional polymorphisms of the EPHX2 gene (rs2741335 and rs11780592) with oxidized LDL (ox-LDL), carotid atherosclerosis, mortality, and cardiovascular (CV) disease in 118 patients with diabetic chronic kidney disease (CKD). At baseline, ox-LDL and carotid intima-media thickness (cIMT) were evaluated and all patients were followed for seven years with outcomes all-cause mortality and CV events. rs11780592 EPHX2 polymorphism was associated with ox-LDL, cIMT, albuminuria, and hypertension. Compared to AG and GG, AA homozygotes had higher values of albuminuria, ox-LDL, and cIMT (p = 0.046, p = 0.003, and p = 0.038, respectively). These associations remained significant, even after grouping for the G allele. After the follow-up period, 42/118 patients died (30/60 with AA genotype, 11/42 with AG genotype, and 1/12 with GG genotype) and 49/118 experienced a new CV event (fatal or nonfatal). The Kaplan-Meier analysis revealed that patients with the AA genotype exhibited a significantly higher mortality risk, compared to patients with AG and GG genotypes (p = 0.006). This association became even stronger, when AG and GG genotypes were grouped (AA vs. AG/GG, p = 0.002). AA homozygotes were strongly associated with all-cause mortality in both univariate (hazard ratio (HR) = 2.74, confidence interval (CI) = 1.40–5.35, p = 0.003) and multivariate Cox regression analysis (HR = 2.61, CI = 1.32–5.17, p = 0.006). In conclusion, our study demonstrated that genetic variations of EPHX2 gene were associated with increased circulating ox-LDL, increased cIMT, and all-cause mortality in diabetic CKD. Since EPHX2 regulates the cholesterol efflux and the oxidation of LDL in foam cells and macrophages, our study suggests that a genetic basis to endothelial dysfunction and OS might be present in diabetic CKD.
High-Throughput Sequencing Indicates Novel Varicosavirus, Emaravirus, and Deltapartitivirus Infections in Vitis coignetiae

Vitis coignetiae samples were collected from several locations in the northern area of Japan, and virome analysis using a high-throughput sequencing technique was performed. The data indicated that some of the collected samples were in mixed infections by various RNA viruses. Among these viruses, three were identified as newly recognized species with support of sequence identity and phylogenetic analysis. The viruses have been provisionally named the Vitis varicosavirus, Vitis emaravirus, and Vitis crypticvirus, and were assigned to the genus Varicosavirus, Emaravirus, and Deltapartitivirus, respectively.
SIRT5 Inhibition Induces Brown Fat-Like Phenotype in 3T3-L1 Preadipocytes

Brown adipose tissue (BAT) activity plays a key role in regulating systemic energy. The activation of BAT results in increased energy expenditure, making this tissue an attractive pharmacological target for therapies against obesity and type 2 diabetes. Sirtuin 5 (SIRT5) affects BAT function by regulating adipogenic transcription factor expression and mitochondrial respiration. We analyzed the expression of SIRT5 in the different adipose depots of mice. We treated 3T3-L1 preadipocytes and mouse primary preadipocyte cultures with the SIRT5 inhibitor MC3482 and investigated the effects of this compound on adipose differentiation and function. The administration of MC3482 during the early stages of differentiation promoted the expression of brown adipocyte and mitochondrial biogenesis markers. Upon treatment with MC3482, 3T3-L1 adipocytes showed an increased activation of the AMP-activated protein kinase (AMPK), which is known to stimulate brown adipocyte differentiation. This effect was paralleled by an increase in autophagic/mitophagic flux and a reduction in lipid droplet size, mediated by a higher lipolytic rate. Of note, MC3482 increased the expression and the activity of adipose triglyceride lipase, without modulating hormone-sensitive lipase. Our findings reveal that SIRT5 inhibition stimulates brown adipogenesis in vitro, supporting this approach as a strategy to stimulate BAT and counteract obesity.
Analysis of Risk Factors for Surgical Complications of Endoscopic Thyroidectomy via Total Areola Approach

Background Increased surgical technology has led broad acceptance endoscopic thyroidectomy and its application in the treatment of thyroid diseases, including thyroid carcinoma. Although the incidence of complications and mortality of thyroid surgery has been significantly reduced, serious complications still occur from time to time. The purpose of this retrospective study is to identify the factors that influence the complications of endoscopic thyroidectomy. Methods This study was carried out between January 2012 and December 2019, where a total of 630 patients undergoing endoscopic thyroidectomy via the total areola approach were retrospectively evaluated to identify the key influencing factors of complications. Results The study established that the common complications included recurrent laryngeal nerve injury (3.33%), superior laryngeal nerve injury (2.54%), hypocalcemia (8.57%), and the incidence of complications was acceptable. Both univariate and multivariate analysis showed that thyroid carcinoma (P = 0.041), operation time lasting more than 150 minutes (P = 0.034) and operation before 2017 (P = 0.001) were risk factors of recurrent laryngeal nerve injury. We established that operation after 2017 (P < 0.005) was the only protective factor of superior laryngeal nerve injury. Thyroid carcinoma (P=0.04), operation mode (P=0.001), and surgery before 2017 (P<0.001) are risk factors for parathyroid injury. Among the clinical groups, operation before 2017 was an independent risk factor for all complications. Conclusion For thyroid specialists, after the early learning curve, with the continuous improvement of endoscopic operation technology, high-definition equipment and more sophisticated operation equipment can be used in clinical practice, which can prevent and reduce the occurrence of complications.
Diet–Microbiota Interactions in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although the precise etiology of IBD is largely unknown, it is widely thought that diet contributes to the development of IBD. Diet shapes the composition of the gut microbiota, which plays critical roles in intestinal homeostasis. In contrast, intestinal inflammation induces gut dysbiosis and may affect the use of dietary nutrients by host cells and the gut microbiota. The interaction of diet and the gut microbiota is perturbed in patients with IBD. Herein, we review the current knowledge of diet and gut microbiota interaction in intestinal homeostasis. We also discuss alterations of diet and gut microbiota interaction that influence the outcome and the nutritional treatment of IBD. Understanding the complex relationships between diet and the gut microbiota provides crucial insight into the pathogenesis of IBD and advances the development of new therapeutic approaches.
COVID-19 and Obesity: An Epidemiologic Analysis of the Brazilian Data

Brazil has the second highest number of deaths due to COVID-19. Obesity has been associated with an important role in disease development and a worse prognosis. We aimed to explore epidemiological data from Brazil, discussing the potential relationships between obesity and COVID-19 severity in this country. We used a public database made available by the Ministry of Health of Brazil (182700 patients diagnosed with COVID-19). Descriptive statistics were used to characterize our database. Continuous data were expressed as median and analyzed by the nonparametric tests Mann–Whitney or one-sample Wilcoxon. The frequencies of categorical variables have been analyzed by chi-square tests of independence or goodness-of-fit. Among the number of deaths, 74% of patients were 60 years of age or older. Patients with obesity who died of COVID-19 were younger (59 years (IQR = 23)) than those without obesity (71 years (IQR = 20), P < 0.001, and η2 = 0.0424). Women with obesity who died of COVID-19 were older than men (55 years (IQR = 25) vs. 50 (IQR = 22), P < 0.001, and η2 = 0.0263). Furthermore, obesity increases the chances of needing intensive care unit (OR: 1.783, CI: 95%, and P < 0.001), needing ventilatory support (OR: 1.537, CI: 95%, and P < 0.001 and OR: 2.302, CI: 95%, and P < 0.001, for noninvasive and invasive, respectively), and death (OR: 1.411, CI: 95%, and P < 0.001) of patients hospitalized with COVID-19. Our analysis supports obesity as a significant risk factor for the development of more severe forms of COVID-19. The present study can direct a more effective prevention campaign and appropriate management of subjects with obesity.