Miracle-dz/UniFAR-FTUs huggingface dataset:
How Microbes Use Force To Control Adhesion

Microbial adhesion and biofilm formation are usually studied using molecular and cellular biology assays, optical and electron microscopy, or laminar flow chamber experiments. Today, atomic force microscopy (AFM) represents a valuable addition to these approaches, enabling the measurement of forces involved in microbial adhesion at the single-molecule level. In this minireview, we discuss recent discoveries made applying state-of-the-art AFM techniques to microbial specimens in order to understand the strength and dynamics of adhesive interactions. ABSTRACT Microbial adhesion and biofilm formation are usually studied using molecular and cellular biology assays, optical and electron microscopy, or laminar flow chamber experiments. Today, atomic force microscopy (AFM) represents a valuable addition to these approaches, enabling the measurement of forces involved in microbial adhesion at the single-molecule level. In this minireview, we discuss recent discoveries made applying state-of-the-art AFM techniques to microbial specimens in order to understand the strength and dynamics of adhesive interactions. These studies shed new light on the molecular mechanisms of adhesion and demonstrate an intimate relationship between force and function in microbial adhesins.
Maternal Thyroid Disorders and Risk of Autism Spectrum Disorder in Progeny

Supplemental Digital Content is available in the text. Background: Maternal thyroid dysfunction is suspected of causing adverse neurodevelopmental effects, but current evidence is inconclusive. Epidemiologic investigations generally suggest an association between maternal thyroid dysfunction and neurodevelopment impairments in progeny, but clinical trials of thyroid treatment during pregnancy reported null effects. To better understand these discrepant findings, we evaluated the association between maternal thyroid conditions and autism spectrum disorder (ASD), including examining the role of gestational thyroid-related hormone concentrations and thyroid medications use. Methods: Analyses considered 437,222 singleton live births occurring in a large Israeli health fund in 1999–2013, followed through 2016. Thyroid conditions and ASD cases were identified through International Classification of Diseases-9 codes with subsequent validation through review of medical records. Laboratory gestational thyroid hormone measurements were also considered. Results: Children of mothers who ever experienced hypothyroidism had a higher risk of ASD compared with children of mothers without hypothyroidism (adjusted odds ratio [aOR] = 1.26, 95% confidence interval [CI] = 1.12, 1.42). The association with hyperthyroidism was less consistent, but elevated in main analyses (aOR = 1.42, 95% CI = 1.04, 1.94). These associations were not explained by maternal gestational thyroid hormones levels nor mitigated by gestational use of thyroid medications. Conclusions: Results indicate that maternal thyroid conditions are associated with increased ASD risk in progeny, but suggestively not due to direct effects of thyroid hormones. Instead, factors that influence maternal thyroid function could have etiologic roles in ASD through pathways independent of maternal gestational thyroid hormones and thus be unaffected by medication treatment. Factors known to disrupt thyroid function should be examined for possible involvement in ASD etiology.
Bladder Cancer Involving Smooth Muscle of Indeterminate Type or Muscularis Mucosae in Transurethral Biopsy Specimens.

OBJECTIVES Bladder cancers invading the muscularis mucosae (MM) are treated differently from those invading the muscularis propria (MP). However, it may be difficult to determine the type of smooth muscle in transurethral resection (TUR) or biopsy specimens. We aimed to investigate the clinicopathologic features of bladder cancers involving smooth muscle of indeterminate type (SMIT) in TUR specimens in comparison with those invading the MM. METHODS We identified 103 patients with bladder cancer involving SMIT (n = 27) or the MM (n = 76) in TUR specimens. All patients underwent subsequent restaging TUR or cystectomy. RESULTS Bladder cancer with SMIT invasion showed a significantly higher rate of MP invasion in the subsequent specimens than those invading the MM (52% vs 29%). Lack of MP in the TUR specimens had a significantly higher risk of MP invasion in the subsequent specimens than those with the MP (61% vs 40%). The overall survival time for patients with SMIT invasion was significantly shorter than those with MM invasion. CONCLUSIONS Bladder cancers with SMIT invasion in TUR specimens show more frequent cancer upstaging in the subsequent specimens and a poorer clinical outcome than those invading the MM, which highlights the importance of a cancer restaging procedure for these patients.
BAI1 acts as a tumor suppressor in lung cancer A549 cells by inducing metabolic reprogramming via the SCD1/HMGCR module.

Brain angiogenesis inhibitor 1 (BAI1) is an important tumor suppressor in multiple cancers. However, the mechanisms behind its anti-tumor activity, particularly the relationship between BAI1 and metabolic aberrant of a tumor, remained unveiled. This study aimed to investigate whether BAI1 could inhibit biological functions in lung cancer A549 cells and the critical regulating molecules that induce metabolic reprogramming. Immunohistochemistry staining was performed to analyze whether variations in the expression of BAI1 in tumor tissues contributes to poor prognosis of lung cancer. Overexpressed BAI1 (BAI1-OE-A549) and control (Vector-NC-A549) were generated by lentiviral transfection. Biological function assays (proliferation, apoptosis, colony formation, invasion and in vivo metastasis), as well as metabolic reprogramming (by the Warburg effect and the glycolytic rate), were performed in both groups. Our results indicated that lower levels of BAI1 contributed to poor prognosis of lung cancer patients. Furthermore, overexpressed of BAI1 dramatically inhibited proliferation, migration, invasion, colony formation, and in vivo metastasis of A549 cells. The Warburg effect and the Seahorse assay revealed that BAI1-OE induced metabolism reprogramming by inhibiting the Warburg effect and glycolysis. Further exploration indicated that BAI1 induced metabolic reprogramming by upregulating stearoyl-CoA desaturase 1 (SCD1) and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Our study revealed a novel mechanism through which BAI1 acted as tumor-suppressor by inducing metabolic reprogramming via the SCD1 and HMGCR module.
Can machine-learning methods really help predict suicide?

PURPOSE OF REVIEW In recent years there has been interest in the use of machine learning in suicide research in reaction to the failure of traditional statistical methods to produce clinically useful models of future suicide. The current review summarizes recent prediction studies in the suicide literature including those using machine learning approaches to understand what value these novel approaches add. RECENT FINDINGS Studies using machine learning to predict suicide deaths report area under the curve that are only modestly greater than, and sensitivities that are equal to, those reported in studies using more conventional predictive methods. Positive predictive value remains around 1% among the cohort studies with a base rate that was not inflated by case-control methodology. SUMMARY Machine learning or artificial intelligence may afford opportunities in mental health research and in the clinical care of suicidal patients. However, application of such techniques should be carefully considered to avoid repeating the mistakes of existing methodologies. Prediction studies using machine-learning methods have yet to make a major contribution to our understanding of the field and are unproven as clinically useful tools.
SOCIO-DEMOGRAPHIC CHARACTERISTICS AND REPORTED PSY-CHO-MEDICAL SYMPTOMS FOR CHILDREN WITH RARE DISEASES. A COMPARATIVE STUDY BETWEEN PATIENTS WITH PHENYLKE-TONURIA, CYSTIC FIBROSIS AND HYPOTHYROIDISM

Rare diseases have great impact on both patients and family members’ life. The aim of the study was to identify socio-demographic characteristics and factors related to psychological and medical condition for pediatric patients diagnosed with phenylketonuria, cystic fibrosis and hypothyroidism. Material and methods: 37 children (24 boys and 13 girls) aged M = 7.61 ± 6.37 (1-22-years-old) were included in the research. A total of 44.7% are diagnosed with cystic fibrosis, 31.6% with phenylketonuria and 23.7% with hypothyroidism. Socio-demographic characteristics and psychological and medical data reported by mothers were registered to point the presence of some characteristics related to the diseases and to identify differences between the three categories of patients. Data have been processed using SPSS Statistics v23.0. 0 for MAC.OSX. Results: Almost 1/5 of children diagnosed with hypothyroidism and phenylketonuria were found to have depression symp-toms and 1/3 of patients with hypothyroidism are having cognitive impairment associated in 40% of cases with language difficulties, and 20% of them present difficulties to adapt to so-cial environment. A total of 18.3% of children with cystic fibrosis presented enuresis and 20% of them has bruxism. Conclusions: children with rare disease present several psycho-logical symptoms and social difficulties, psychotherapeutically and educational support for both patients and families are needed.
Assessment of White Matter Integrity Following Pediatric Traumatic Brain Injury.

White matter (WM) abnormalities, such as atrophy and hyperintensities (WMH), can be accessed via magnetic resonance imaging (MRI) following pediatric traumatic brain injury (TBI). Several methods are available to classify WM abnormalities (i.e. total WM volumes and WMHs), but automated and manual volumes and clinical ratings have yet to be compared in pediatric TBI. Additionally, WM integrity has been reliably associated with processing speed. Consequently, methods of assessing WM integrity should relate to processing speed to have clinical application. This study had two goals: (1) to compare Scheltens rating scale, manual tracing, FreeSurfer, and NeuroQuant® methods of assessing WM abnormalities, (2) to relate WM methods to processing speed scores. We report findings from the Social Outcomes of Brain Injury in Kids (SOBIK) study, a multicenter study of 60 children with chronic TBI (65% male) from ages 8-13. Scheltens WMH ratings had good to excellent agreement with WMH volumes for both NeuroQuant® (ICC = .62; r = .29, p = .005) and manual tracing (ICC = .82; r = .50, p = .000). NeuroQuant® WMH volumes did not correlate with manually traced WMH volumes (r = .12, p = .21) and had poor agreement (ICC = .24). NeuroQuant® and FreeSurfer total WM volumes correlated (r = .38, p = .004) and had fair agreement (ICC = .52). WMH assessment methods, both ratings and volumes, were associated with processing speed scores. In contrast, total WM volume was not related to processing speed. Measures of WMH may hold clinical utility for predicting cognitive functioning after pediatric TBI.
CDK6 Inhibition: A Novel Approach in AML Management

Acute myeloid leukemia (AML) is a complex disease with an aggressive clinical course and high mortality rate. The standard of care for patients has only changed minimally over the past 40 years. However, potentially useful agents have moved from bench to bedside with the potential to revolutionize therapeutic strategies. As such, cell-cycle inhibitors have been discussed as alternative treatment options for AML. In this review, we focus on cyclin-dependent kinase 6 (CDK6) emerging as a key molecule with distinct functions in different subsets of AML. CDK6 exerts its effects in a kinase-dependent and -independent manner which is of clinical significance as current inhibitors only target the enzymatic activity.
Gemcitabine‐based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score‐matched cohort study

Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score‐matched analysis.
Quasi-Periodic Dendritic Metasurface for Integral Operation in Visible Light

A reflective metasurface model composed of silver dendritic units is designed in this study. The integral property of this metasurface, which consists of an upper layer of dendritic structures, a silica spacer, and a bottom silver substrate was demonstrated at visible wavelengths. The simulation results revealed that the metasurface can perform integral operation in the yellow and red bands; this can be easily generalized to the infrared and communication bands by scaling the transverse dimensions of this metasurface. A dendritic metasurface sample responding to red light was prepared via the bottom-up electrochemical deposition method. The integral operation property of the sample was verified experimentally. This dendritic metasurface, which can perform integral operation in visible light, can be used for big data processing technology, real-time signal processing, and beam shaping, and provides a new method for miniaturized and integrated all-optical signal processing systems.
Histone demethylase SlJMJ6 promotes fruit ripening by removing H3K27 methylation of ripening-related genes in tomato.

Fruit ripening is governed by a complex regulatory network. Reversible histone methylation and demethylation regulate chromatin structure and gene expression. However, little is known about the involvement of histone demethylases in regulating fruit ripening. Here, we found that the tomato SlJMJ6 encodes a histone lysine demethylase that specifically demethylates H3K27 methylation. Overexpression of SlJMJ6 accelerates tomato fruit ripening, which is associated with the upregulated expression of a large number of ripening-related genes. Integrated analysis of RNA-seq and ChIP-seq identified 32 genes directly targeted by SlJMJ6 and transcriptionally upregulated with decreased H3K27m3 in SlJMJ6-overexpressed fruit. Numerous SlJMJ6-regulated genes are involved in transcription regulation, ethylene biosynthesis, cell wall degradation, and hormone signaling. Eleven ripening-related genes including RIN, ACS4, ACO1, PL, TBG4, and a DNA demethylase DML2, were confirmed to be directly regulated by SlJMJ6 through removing H3K27me3. Our results demonstrate that SlJMJ6 is a ripening-prompting H3K27me3 demethylase that activates the expression of the ripening-related genes by modulating H3K27me3, thereby facilitating tomato fruit ripening. Our work also reveals a novel link between histone demethylation and DNA demethylation in regulating fruit ripening. To our knowledge, this is the first report of the involvement of a histone lysine demethylase in the regulation of fruit ripening.
An unusual case of aggregatibacter aphrophilus liver abscess

Liver abscess of oropharyngeal origin in an immunocompetent patient is a rare condition. Furthermore, microbiologic diagnosis of liver abscess can be challenging due to the tremendous diversity of the microorganisms implicated and culture difficulties under laboratory conditions. We report a case of a previously healthy 23-year-old male, who presented multiple liver abscesses, attributed to aggregatibacter aphrophilus, an obligatory oral gram-negative microorganism, that normally is a component of the commensal oral microbiota and non-virulent. The etiopathogenic microorganism was identified after needle aspiration of a liver abscess cavity. Treatment with broad-spectrum antimicrobials and percutaneous catheter drainage under computed tomography guidance of both abscesses, resulted in full recovery. A. aphrophilus represents a rare entity of liver abscess in healthy individuals and suggests that a pathogen of oropharyngeal origin should be suspected when an overt source of infection cannot be documented.
Ecklonia stolonifera Extract Suppresses Lipid Accumulation by Promoting Lipolysis and Adipose Browning in High-Fat Diet-Induced Obese Male Mice

Obesity develops due to an energy imbalance and manifests as the storage of excess triglyceride (TG) in white adipose tissue (WAT). Recent studies have determined that edible natural materials can reduce lipid accumulation and promote browning in WAT. We aimed to determine whether Ecklonia stolonifera extract (ESE) would increase the energy expenditure in high-fat diet (HFD)-induced obese mice and 3T3-L1 cells by upregulating lipolysis and browning. ESE is an edible brown marine alga that belongs to the family Laminariaceae and contains dieckol, a phlorotannin. We report that ESE inhibits body mass gain by regulating the expression of proteins involved in adipogenesis and lipogenesis. In addition, ESE activates protein kinase A (PKA) and increases the expression of lipolytic enzymes including adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and monoacylglycerol lipase (MGL) and also thermogenic genes, such as carnitine palmitoyltransferase 1 (CPT1), PR domain-containing 16 (PRDM16), and uncoupling protein 1 (UCP1). These findings indicate that ESE may represent a promising natural means of preventing obesity and obesity-related metabolic diseases.
Microbial Resources as a Tool for Enhancing Sustainability in Winemaking

In agriculture, the wine sector is one of the industries most affected by the sustainability issue. It is responsible for about 0.3% of annual global greenhouse gas emissions from anthropogenic activities. Sustainability in vitiviniculture was firstly linked to vineyard management, where the use of fertilizers, pesticides and heavy metals is a major concern. More recently, the contribution of winemaking, from grape harvest to bottling, has also been considered. Several cellar processes could be improved for reducing the environmental impact of the whole chain, including microbe-driven transformations. This paper reviews the potential of microorganisms and interactions thereof as a natural, environmentally friendly tool to improve the sustainability aspects of winemaking, all along the production chain. The main phases identified as potentially interesting for exploiting microbial activities to lower inputs are: (i) pre-fermentative stages, (ii) alcoholic fermentation, (iii) stage between alcoholic and malolactic fermentation, (iv) malolactic fermentation, (v) stabilization and spoilage risk management, and (vi) by-products and wastewater treatment. The presence of proper yeast or bacterial strains, the management and timing of inoculation of starter cultures, and some appropriate technological modifications that favor selected microbial activities can lead to several positive effects, including (among other) energy savings, reduction of chemical additives such as sulfites, and reuse of certain residues.
Early pH Changes in Musculoskeletal Tissues upon Injury—Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release.
Clinical Practice Guideline for Endoscopic Resection of Early Gastrointestinal Cancer

Although surgery was the standard treatment for early gastrointestinal cancers, endoscopic resection is now a standard treatment for early gastrointestinal cancers without regional lymph node metastasis. High-definition white light endoscopy, chromoendoscopy, and image-enhanced endoscopy such as narrow band imaging are performed to assess the edge and depth of early gastrointestinal cancers for delineation of resection boundaries and prediction of the possibility of lymph node metastasis before the decision of endoscopic resection. Endoscopic mucosal resection and/or endoscopic submucosal dissection can be performed to remove early gastrointestinal cancers completely by en bloc fashion. Histopathological evaluation should be carefully made to investigate the presence of risk factors for lymph node metastasis such as depth of cancer invasion and lymphovascular invasion. Additional treatment such as radical surgery with regional lymphadenectomy should be considered if the endoscopically resected specimen shows risk factors for lymph node metastasis. This is the first Korean clinical practice guideline for endoscopic resection of early gastrointestinal cancer. This guideline was developed by using mainly de novo methods and encompasses endoscopic management of superficial esophageal squamous cell carcinoma, early gastric cancer, and early colorectal cancer. This guideline will be revised as new data on early gastrointestinal cancer are collected.
COVID-19 Pandemic: Public Health Implications in Nepal

Over the past few decades, we have seen several outbreaks of zoonotic coronavirus infections. These viruses have the potential of interspecies transmission leading to pathogenesis in humans. This particular respiratory coronavirus initially named 2019-nCOV, is known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current situation, abiding to the general health guidelines is utmost important to maintain stronger immunity for fighting infections and protection from other environmental hazards.
High-specific-activity iodine 131 metaiodobenzylguanidine for the treatment of metastatic pheochromocytoma or paraganglioma: a novel therapy for an orphan disease.

PURPOSE OF REVIEW Pheochromocytomas and paragangliomas represent less than 1% of all endocrine tumors. Approximately 15-20% of these tumors are malignant. The definition of malignancy relies on the presence of metastasis. Metastatic pheochromocytomas and paragangliomas are usually advanced, incurable tumors with limited therapeutic options. About 50-60% of these tumors express the noradrenaline transporter in their cell membranes. Recently, the United States Food and Drug Administration approved high-specific-activity iodine 131 metaiodobenzylguanidine (HSA-I-131-MIBG) for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter. This review reports the benefits and toxicity of HSA-I-131-MIBG, its physical and dosimetric aspects, and radiation safety precautions, as well as its potential therapeutic value for other malignancies (neuroblastoma, gastroenteropancreatic neuroendocrine tumors, and medullary thyroid carcinoma). RECENT FINDINGS A phase 2 clinical trial with HSA-I-131-MIBG reported an impressive clinical benefit rate, acceptable toxicity and long-term benefits. SUMMARY HSA-I-131-MIBG is an effective medication for metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter.