Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Serotonin Transporter (SERT) Polymorphisms with Opioid Dependence and Dimensional Aspects of Cocaine Use in a Caucasian Cohort of Opioid Users

Introduction A functional tandem repeat polymorphism in the promoter of the serotonin transporter (SERT) gene (SLC6A4) has been studied for association to neuropsychiatric conditions, including substance use disorders. Short (S) forms of this repeat result in reduced transcription, and presumably greater synaptic levels of serotonin, which are involved in opioid and cocaine-induced reward. Dual exposure to heroin and cocaine is a common pattern of poly-drug use and is associated with considerable morbidity. We hypothesize that SLC6A4 variants are associated with cocaine exposure in subjects with an opioid dependence diagnosis (OD), and also in non-dependent opioid users (NOD). Other single nucleotide polymorphisms (SNPs) of SLC6A4 may also be likewise associated. Materials and Methods This study determined whether variants of the SLC6A4 promoter repeats and two intronic SNPs, rs16965628 and rs2066713, are associated with categorical diagnoses of opioid dependence (DSM-IV criteria) and with dimensional aspects of cocaine use, in a Caucasian cohort (n=591). Three groups of subjects were examined: (1) 276 subjects with opioid dependence diagnosis (OD); (2) 163 subjects who had used opioids for non-medical reasons but never had an opioid dependence diagnosis (NOD); (3) 152 healthy controls (HC). Results Aside from high exposure to heroin in the OD group, relatively high exposure to cocaine was detected in both OD and NOD groups. The SERT repeat genotype (classified as “long-long” [LL] versus ”short-long” plus “short-short” [SL+SS]) was not associated with categorical opioid dependence diagnoses. A nominally signiﬁcant association was identiﬁed with the [SL+SS] genotype of SLC6A4 and cocaine KMSK scores ≥“cutpoint” for a cocaine dependence diagnosis (p=0.026). The [SL+SS] genotype was associated with more rapid cocaine escalation than the LL genotype. No signiﬁcant associations of rs16965628 and rs2066713 SNPs were found overall. Conclusion The functional SERT promoter tandem repeat genotype may be associated to heavy cocaine exposure and more rapid escalation of cocaine use, in persons with and without opioid dependence diagnosis.
Development of Fish Parasite Vaccines in the OMICs Era: Progress and Opportunities

Globally, parasites are increasingly being recognized as catastrophic agents in both aquaculture sector and in the wild aquatic habitats leading to an estimated annual loss between 1.05 billion and 9.58 billion USD. The currently available therapeutic and control measures are accompanied by many limitations. Hence, vaccines are recommended as the “only green and effective solution” to address these concerns and protect fish from pathogens. However, vaccine development warrants a better understanding of host–parasite interaction and parasite biology. Currently, only one commercial parasite vaccine is available against the ectoparasite sea lice. Additionally, only a few trials have reported potential vaccine candidates against endoparasites. Transcriptome, genome, and proteomic data at present are available only for a limited number of aquatic parasites. Omics-based interventions can be significant in the identification of suitable vaccine candidates, finally leading to the development of multivalent vaccines for significant protection against parasitic infections in fish. The present review highlights the progress in the immunobiology of pathogenic parasites and the prospects of vaccine development. Finally, an approach for developing a multivalent vaccine for parasitic diseases is presented. Data sources to prepare this review included Pubmed, google scholar, official reports, and websites.
Extrahepatic cytochrome P450 epoxygenases: pathophysiology and clinical significance in human gastrointestinal cancers

Cytochrome P450 (CYP) epoxygenases, a multi-gene superfamily of heme-containing enzymes, are commonly known to metabolize endogenous arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs). The role of CYPs is mostly studied in liver drugs metabolism, cardiac pathophysiology, and hypertension fields. Particularly, the biological functions of these enzymes have increasingly attracted a growing interest in cancer biology. Most published studies on CYPs in cancer have been limited to their role as drug metabolizing systems. The activity of these enzymes may affect drug pharmacokinetics and bioavailability as well as exogenous compounds turnover. Some CYP isoforms are selectively highly expressed in tumors, suggesting a potential mechanistic role in promoting resistance to chemotherapy. Majority of drugs elicit their effects in extrahepatic tissues whereby their metabolism can significantly determine treatment outcome. Nonetheless, the role of extrahepatic CYPs is not fully understood and targeting these enzymes as effective anti-cancer therapies are yet to be developed. This review article summarizes an up-to-date body of information from published studies on CYP enzymes expression levels and pathophysiological functions in human normal and malignant gastrointestinal (GI) tract tissues. Specifically, we reviewed and discussed the current research initiatives by emphasizing on the clinical significance and the pathological implication of CYPs in GI malignancies of esophagus, stomach, and colon.
Antimicrobial Stewardship Programmes in Saudi Hospitals: Evidence from a National Survey

Saudi hospitals and healthcare facilities are facing increasing rates of antimicrobial resistance and the emergence of new multi-drug resistant strains. This is placing an unprecedented threat to successful treatments and outcomes of patients accessing those facilities. The inappropriate use of antimicrobials is fueling this crisis, warranting urgent implementation of interventions to preserve antimicrobials and reduce resistance rates. Antimicrobial stewardship programmes (ASPs) can improve antimicrobial use, treatment success rates and reduce the levels of antimicrobial resistance. The Saudi Ministry of Health (MOH) devised a national antimicrobial stewardship plan to implement ASPs in hospitals, but little is known about the progress of implementation and the factors affecting it. This study aims to assess the level and the factors affecting the adoption and implementation of ASPs in Saudi hospitals at a national level. A nationwide cross-sectional survey was conducted in 2017 using an online questionnaire sent to all MOH hospitals. Overall, 147 out 247 MOH hospitals responded to the survey (54%). Only 26% of the hospitals reported the implementation of ASPs. Hospitals lack the knowledge, technological and staff resources to adopt and implement ASPs. Alternative models of ASP adoption could be explored to improve the rates of implementation of ASPs.
“Double Prosthesis Implantation”: Biometry and Refractive Outcomes in Combined Intraocular Lens and Artificial Iris Surgery

Purpose To assess the biometry and postoperative refraction in iris repair using ArtificialIris in combination with an intraocular lens (IOL). Setting Department of Ophthalmology, University Hospital Heidelberg, University of Heidelberg, Germany. Design Retrospective observational study. Methods We included 44 aniridic and aphakic eyes for IOL implantation in combination with iris prosthesis reconstruction. The iris prostheses were either sutured into the ciliary sulcus and fixed by transscleral suturing or were implanted together with a capsular tension ring and the IOL in the capsular bag. The primary outcomes measured were pre- and postoperative best corrected visual acuity (CDVA), objective and subjective refraction, anterior chamber depth and optical biometry comparing common IOL formulae. Results Reasons for surgery were trauma (39 eyes), iatrogenic causes (1 eye), aniridic state after severe iritis (2 eyes) or iris tumor (2 eyes). Monocular CDVA improved significantly (p<0.0001) from median 0.55 logMAR (0.0 to 1.98) to 0.16 logMAR (−0.08 to 2.0). There were no significant differences between the postoperative target refraction calculated by the formulae “Haigis”, “Hoffer-Q”, “SRK/T” and “Holladay 1” (p=0.68). The absolute deviation from target refraction did not differ significantly between the formulae (p=0.87). Median target refraction was −0.42 D (−4.0 to 1.68). Postoperatively median spherical equivalent was 0.00 D (−5.38 to 2.38). Median absolute deviation from target refraction after 5 months of follow-up was 0.98 D (0.06 to 5.17). Conclusion Postoperative refraction using common techniques and using preoperative biometry revealed a well predictable postoperative refraction. There is no correction factor needed.
Roles of Phosphate Solubilizing Microorganisms from Managing Soil Phosphorus Deficiency to Mediating Biogeochemical P Cycle

Simple Summary Phosphate solubilizing microorganisms (PSMs), a large microflora that mediate bioavailable soil P, play a critical role in soil by mineralizing organic P, solubilizing inorganic P minerals, and storing large amounts of P in biomass. Given that the basic soil P forms and orthophosphate levels can be mediated by PSMs, we conclude that PSMs also play a critical role in the soil P cycle. The present review summarizes the comprehensive and recent understanding about the roles of PSMs in P geochemical processes. Abstract Phosphorus (P) is a vital element in biological molecules, and one of the main limiting elements for biomass production as plant-available P represents only a small fraction of total soil P. Increasing global food demand and modern agricultural consumption of P fertilizers could lead to excessive inputs of inorganic P in intensively managed croplands, consequently rising P losses and ongoing eutrophication of surface waters. Despite phosphate solubilizing microorganisms (PSMs) are widely accepted as eco-friendly P fertilizers for increasing agricultural productivity, a comprehensive and deeper understanding of the role of PSMs in P geochemical processes for managing P deficiency has received inadequate attention. In this review, we summarize the basic P forms and their geochemical and biological cycles in soil systems, how PSMs mediate soil P biogeochemical cycles, and the metabolic and enzymatic mechanisms behind these processes. We also highlight the important roles of PSMs in the biogeochemical P cycle and provide perspectives on several environmental issues to prioritize in future PSM applications.
Recent Advances in Small Peptides of Marine Origin in Cancer Therapy

Cancer is one of the leading causes of death in the world, and antineoplastic drug research continues to be a major field in medicine development. The marine milieu has thousands of biological species that are a valuable source of novel functional proteins and peptides, which have been used in the treatment of many diseases, including cancer. In contrast with proteins and polypeptides, small peptides (with a molecular weight of less than 1000 Da) have overwhelming advantages, such as preferential and fast absorption, which can decrease the burden on human gastrointestinal function. Besides, these peptides are only connected by a few peptide bonds, and their small molecular weight makes it easy to modify and synthesize them. Specifically, small peptides can deliver nutrients and drugs to cells and tissues in the body. These characteristics make them stand out in relation to targeted drug therapy. Nowadays, the anticancer mechanisms of the small marine peptides are still largely not well understood; however, several marine peptides have been applied in preclinical treatment. This paper highlights the anticancer linear and cyclic small peptides in marine resources and presents a review of peptides and the derivatives and their mechanisms.
The complete chloroplast genome sequence of Ficus altissima (Moraceae)

Abstract Ficus altissima plays an important role on biodiversity in tropical forests. In this study, the complete chloroplast genome sequence and the genome features of F. altissima were analyzed using the Illumina NovaSeq platform. The whole chloroplast genome sequence of F. altissima is 160,251 including a large single-copy region (LSC, 88,468 bp), a small single-copy region (SSC, 20,009 bp), and a pair of repeat regions (IRs, 25,887 bp, each). Further gene annotation revealed the chloroplast genome contains 124 genes, including 79 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. A total of 82 simple sequence repeats (SSRs) were identified in the chloroplast genome. Phylogenetic development was analyzed based on F. altissima with other species of Moraceae. This information will be useful for study on the evolution and genetic diversity of F. altissima in the future.
Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (disc1) Mutant Zebrafish

Synthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (DISC1) is a gene with important roles in neurodevelopment that has been associated with psychiatric disorders in pedigree analyses. Using zebrafish as a model, we investigated (1) the behavioral impact of developmental exposure to 3 μM 1-pentyl-3-(1-naphthoyl)-indole (JWH-018; a common psychoactive synthetic cannabinoid) and (2) whether disc1 moderates the effects of JWH-018. As altered anxiety responses are seen in several psychiatric disorders, we focused on zebrafish anxiety-like behavior. Zebrafish embryos were exposed to JWH-018 from one to six days post-fertilization. Anxiety-like behavior was assessed using forced light/dark and acoustic startle assays in larvae and novel tank diving in adults. Compared to controls, both acutely and developmentally exposed zebrafish larvae had impaired locomotion during the forced light/dark test, but anxiety levels and response to startle stimuli were unaltered. Adult zebrafish developmentally exposed to JWH-018 spent less time on the bottom of the tank, suggesting decreased anxiety. Loss-of-function in disc1 increased anxiety-like behavior in the tank diving assay but did not alter sensitivity to JWH-018. Results suggest developmental exposure to JWH-018 has a long-term behavioral impact in zebrafish, which is not moderated by disc1.
Multi-Omics Characterization and Origin Assessment of Bilateral Lung Adenoid Cystic Carcinoma: A Case Report

Background Primary adenoid cystic carcinoma (ACC) of the lung, which arises from the bronchial gland and is rare, accounting for only 0.04–0.2% of all primary lung tumors. The genetic profiling of bilateral ACC of unknown primary site and application in postoperative decision-making are less reported. Case Presentation A 57-year-old male with a smoking history of over 30 years and multiple nodules in both lungs was present to our department. After assessing the bilateral solid nodules in his Positron Emission Tomography–Computed Tomography (PET/CT) scan, malignant lesions at the left lower lung, right lower lung, and right middle lung are suspected. Sequential selective video-assisted thoracoscopic surgeries (VATS) were performed. A genetic alteration test of 425 cancer-related genes and global gene expression profile of the specimens revealed intrapulmonary metastasis existed. The patient was followed up for three years without recurrence and tissue mutations in liquid biopsy. Conclusion We present a way of omics-based multiple pulmonary lesions origin assessment, facilitating post-operative differential diagnosis and treatment decision for difficult cases.
Control of Cell Growth and Proliferation by the Tribbles Pseudokinase: Lessons from Drosophila

Simple Summary Tribbles pseudokinases represent a sub-branch of the CAMK (Ca2+/calmodulin-dependent protein kinase) subfamily and are associated with disease-associated signaling pathways associated with various cancers, including melanoma, lung, liver, and acute leukemia. The ability of this class of molecules to regulate cell proliferation was first recognized in the model organism Drosophila and the fruit fly genetic model and continues to provide insight into the molecular mechanism by which this family of adapter molecules regulates both normal development and disease associated with corruption of their proper regulation and function. Abstract The Tribbles (Trib) family of pseudokinase proteins regulate cell growth, proliferation, and differentiation during normal development and in response to environmental stress. Mutations in human Trib isoforms (Trib1, 2, and 3) have been associated with metabolic disease and linked to leukemia and the formation of solid tumors, including melanomas, hepatomas, and lung cancers. Drosophila Tribbles (Trbl) was the first identified member of this sub-family of pseudokinases and shares a conserved structure and similar functions to bind and direct the degradation of key mediators of cell growth and proliferation. Common Trib targets include Akt kinase (also known as protein kinase B), C/EBP (CAAT/enhancer binding protein) transcription factors, and Cdc25 phosphatases, leading to the notion that Trib family members stand athwart multiple pathways modulating their growth-promoting activities. Recent work using the Drosophila model has provided important insights into novel facets of conserved Tribbles functions in stem cell quiescence, tissue regeneration, metabolism connected to insulin signaling, and tumor formation linked to the Hippo signaling pathway. Here we highlight some of these recent studies and discuss their implications for understanding the complex roles Tribs play in cancers and disease pathologies.
Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell’s scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = −7%, (95% CI −12.00 to −1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.
The Photochemistry of Carbamates, I

Abstract The photodecomposition of 4-dimethylamino-3,5-xylyl-N-methyl carbamate (Zectran) in aerated and degassed solution has been carried out. Three major photoproducts were detected and characterized to be: 4-dirnethylamino-3,5-dimethyl Rhenol, 4-hydroxy-2,6-dimethyl-N-methyl benzamide and 4-monomethylamino-3,5-xylyl-N-methyl carbamate. The phenol and benzamide products suggest that one of the pathways of photodecomposition of Zectran is via a photo-Fries rearrangement. The ortho-benzamide (5-dimethylamino-4,6-dimethyl-2-hydroxy-N-methyl benzamide) which could also be expected to occur in a photo-Fries reaction, was not observed. The excitation wavelength was > 296.7 nm, i.e. radiation available in the solar spectrum. Thus the products observed in this study may be expected to occur in the environment as a result of the action of sunlight on Zectran.
Developing Crash Severity Model Handling Class Imbalance and Implementing Ordered Nature: Focusing on Elderly Drivers

Along with the rapid demographic change, there has been increased attention to the risk of vehicle crashes relative to older drivers. Due to senior involvement and their physical vulnerability, it is crucial to develop models that accurately predict the severity of senior-involved crashes. However, the challenge is how to cope with an imbalanced severity class distribution and the ordered nature of crash severities, as these can complicate the classification of the severity of crashes. In that regard, this study investigates the influence of implementing ordinal nature and handling imbalanced class distribution on the prediction performance. Using vehicle crash data in Ohio, U.S., as an example, the eight machine learning classifiers (logistic and ordered logistic regressions and random forest and ordered random forest with or without handling imbalanced classes) are suggested and then compared with their respective performances. The analysis outcomes show that balancing strategy enhances performance in predicting severe crashes. In contrast, the effects of implementing ordinal nature vary across models. Specifically, the ordered random forest classifier without balancing appears to be superior in terms of overall prediction accuracy, and the ordered random forest with balancing outperforms others in predicting severer crashes.
Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas

Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely understood. Within the “Metabolomic profiles throughout the continuum of colorectal cancer” (MetaboCCC) consortium we analyzed data generated by untargeted, mass spectrometry-based metabolomics using plasma from 88 colorectal cancer patients, 200 patients with high-risk adenomas and 200 patients with low-risk adenomas recruited within the “Colorectal Cancer Study of Austria” (CORSA). Univariate logistic regression models comparing colorectal cancer to adenomas resulted in 442 statistically significant molecular features. Metabolites discriminating colorectal cancer patients from those with adenomas in our dataset included acylcarnitines, caffeine, amino acids, glycerophospholipids, fatty acids, bilirubin, bile acids and bacterial metabolites of tryptophan. The data obtained discovers metabolite profiles reflecting metabolic differences between colorectal cancer and colorectal adenomas and delineates a potentially underlying biological interpretation.