Miracle-dz/UniFAR-FTUs huggingface dataset:
Rethinking Psychiatry

[0 overview as large a field as psychiatry takes special skill. :oming from Canada's 2 largest medical schools, Joel Paris md Paul Garfinkel with Barbara Dorian offer their views. Their perspectives largely converge. To wit, the contributors oerceive the increasing importance of evidence-based care withinpsychiatry and a need for better integrating the science andart ofour profession-combining the neurobiological unIerstanding of the disease with the appreciation of human suffering, a scientific approach with the attentive presence of 1humanistic healer. Psychiatry's welcome return to its founlation in medicine has increased its respect; however, it risks iroducing clinicians not inclined to developing a holistic, . omprehensive understanding of their patients. The healer ole, which has been with us for so long (5), may be lost. The uimanistic calling, more than counting symptoms, searches or meaning to individual distress. To develop fully, our proession must integrate the biological and psychosocial subtrates. The contributions here also appreciate the lemonstrated efficacy of certain techniques of psychother.py and perceive a need for greater effort in this direction.
Can visual interpretation of NucliSens graphs reduce the need for repeat viral load testing?

Background In Zimbabwe, viral load (VL) testing for people living with HIV on antiretroviral therapy is performed at the National Microbiology Reference Laboratory using a NucliSens machine. Anecdotal evidence has shown that invalid graphs for “Target Not Detectable (TND)” will upon repeat VL testing produce a valid result for virus not detected, therefore removing the need to repeat the test. This needs formal assessment. Objectives To determine i) intra- and inter-rater agreement of the visual interpretation of NucliSens graphs (Target Detectable [TD], TND and No Line [NL]) between two laboratory scientists and ii) sensitivity, specificity and predictive values of the NucliSens graphs compared with repeat VL results. Method Cross sectional study using secondary data. Two laboratory scientists independently rated graphs one week apart for intra-rater agreement and compared final ratings with each other for inter-rater agreement. Consensus interpretations of graphs were compared with repeat VL results. Kappa coefficients were used to obtain measures of agreement. Results There were 562 patients with NucliSens graphs and repeat VL. Kappa scores were: 0.98 (Scientist A); 0.99 (Scientist B); 0.96 (Scientist A versus Scientist B); and 0.65 (NucliSens graphs versus VL). Sensitivity, specificity, positive predictive value and negative predictive value for graphs compared with VL were 71%, 92%, 79% and 89% respectively. Conclusion Intra-and inter-rater agreements were almost perfect. The negative predictive value translates to a false negative rate of 11%. If repeat VL testing is not done, the clinical consequences need to be balanced against cost savings and the risks outweigh the benefits.
Clinical Applicability of FANCD2 Mono-Ubiquitination Test for Fanconi Anemia Diagnosis and a Suggestion for

Objectives: Fanconi anemia is caused by mutations in related FANC genes that are involved in DNA repair pathways. Diepoxybutane induced chromosome break test in lymphocytes if positive is affirmative for the diagnosis. However, in 20-25% of the cases the test results have intermediate values which are mostly attributed to somatic mosaicism and cause an ambiguity for diagnosis. Here, we utilize the relatively new and rarely used FANCD2 mono-ubiquitination test to facilitate and resolve the diagnostic problem in a clinical scheme. Methods: Fifteen patients with different diepoxybutane test results (positive, intermediate, negative) and four control subjects were included to the study. Western blot analyses in cultured peripheral blood lymphocyte-isolates were done with a specific antibody to discriminate between ubiquitinated and non-ubiquitinated forms of FANCD2. Results: The test confirmed the diagnosis in one of the diepoxybutane positive patients. In four cases out of seven with intermediate test values we were able to make the right diagnoses. For the other three in this group, FANCD2 test neither confirmed nor rejected the diagnoses which may be due to high somatic mosaicism or due to a defect in the downstream part of the Fanconi pathway. The ubiquitinated isoform of FANCD2 were detected in all six diepoxybutane negative cases. Conclusion: It is expected that adopting FANCD2 mono-ubiquitination Western blot analysis as a diagnostic tool with the proposed algorithm could facilitate the management of Fanconi Anemia without compromise.
Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-β-lactamases: a molecular and evolutionary study

ABSTRACT Resistance to β-lactams is one of the most serious problems associated with Gram-negative infections. β-Lactamases are able to hydrolyze β-lactams such as cephalosporins and/or carbapenems. Evolutionary origin of metallo-β-lactamases (MBLs), conferring critical antibiotic resistance threats, remains unknown. We discovered PNGM-1, the novel subclass B3 MBL, in deep-sea sediments that predate the antibiotic era. Here, our phylogenetic analysis suggests that PNGM-1 yields insights into the evolutionary origin of subclass B3 MBLs. We reveal the structural similarities between tRNase Zs and PNGM-1, and demonstrate that PNGM-1 has both MBL and tRNase Z activities, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 MBLs and tRNase Zs. These comparisons revealed that the B3 MBL activity of PNGM-1 is a promiscuous activity and subclass B3 MBLs are thought to have evolved through PNGM-1 activity.
The effect of alpha‑lipoic acid on oxidative parameters and liver injury in rats with obstructive jaundice.

INTRODUCTION The aim of this study is to investigate the effects of obstructive jaundice on the liver and effectivity of alpha‑lipoic acid on liver damage and oxidative stress. MATERIALS AND METHODS Thirty‑six male Sprague‑Dawley rats were divided into 3 groups per 12 animals, namely into Group I (control group): the bile duct was only mobilized by laparotomy, Group II (bile duct ligation group - BDL): the common bile duct was closed with clips and OJ was caused after laparotomy, and Group III (bile duct ligation and alpha‑lipoic acid group - BDL+LA): after closing the common bile duct, LA was administered in an intramuscular dose of 50 mg/kg for 10 days. On the 10th day, malondialdehyde, glutathione and superoxide dismutase levels were measured in liver and histopathological evaluation was performed. RESULTS AST (U/L)/ALT(U/L) in groups I, II and III were 155.33/51.83, 445.28/165.89, 380.78/173.33, respectively (p < 0.005). Superoxide dismutase and glutathione levels were lower in patient groups than in the control group (0.31 μl/g vs 0.36 µl/g; p < 0.05). After the lipoic acid treatment, none of the biochemical markers of liver improved. Only the increase in superoxide dismutase (0.31 µl/g and 0.34 µl/g in groups II and III, respectively) and glutathione levels (0.16 µl/g and 0.22 µl/g in groups II and III, respectively) was statistically significant (p < 0.05). CONCLUSIONS Histopathological damage was statistically significantly decreased and antioxidant levels were statistically significantly increased after LA treatment (Tab. 1, Fig. 6, Ref. 23).
Binocular 3D Otolith-Ocular Reflexes: Responses of Normal Chinchillas to Tilt and Translation.

Head rotation, translation, and tilt with respect to a gravitational field elicit reflexive eye movements that partially stabilize images of Earth-fixed objects on the retinae of humans and other vertebrates. Compared to the angular vestibulo-ocular reflex, responses to translation and tilt, collectively called the otolith-ocular reflex (OOR), are less completely characterized, typically smaller, generally disconjugate (different for the two eyes) and more complicated in their relationship to the natural stimuli that elicit them. We measured binocular 3-dimensional OOR responses of six alert normal chinchillas in darkness during whole-body tilts around 16 Earth-horizontal axes and translations along 21 axes in horizontal, coronal and sagittal planes. Ocular counter-tilt responses to 40-second whole-body tilts about Earth-horizontal axes grew linearly with head tilt amplitude, but responses were disconjugate, with each eye's response greatest for whole-body tilts about axes near the other eye's resting line of sight. OOR response magnitude during 1 Hz sinusoidal whole-body translations along Earth-horizontal axes also grew with stimulus amplitude. Translational OOR responses were similarly disconjugate, with each eye's response greatest for whole-body translations along its resting line of sight. Responses to Earth-horizontal translation were similar to those that would be expected for tilts that would cause a similar peak deviation of the gravitoinertial acceleration (GIA) vector with respect to the head, consistent with the "perceived tilt" model of the OOR. However, that model poorly fit responses to translations along non-Earth-horizontal axes and was insufficient to explain why responses are larger for the eye toward which the GIA vector deviates.
Activation of anthrachamycin biosynthesis in Streptomyces chattanoogensis L10 by site-directed mutagenesis of rpoB

Genome sequencing projects revealed massive cryptic gene clusters encoding the undiscovered secondary metabolites in Streptomyces. To investigate the metabolic products of silent gene clusters in Streptomyces chattanoogensis L10 (CGMCC 2644), we used site-directed mutagenesis to generate ten mutants with point mutations in the highly conserved region of rpsL (encoding the ribosomal protein S12) or rpoB (encoding the RNA polymerase β-subunit). Among them, L10/RpoB (H437Y) accumulated a dark pigment on a yeast extract-malt extract-glucose (YMG) plate. This was absent in the wild type. After further investigation, a novel angucycline antibiotic named anthrachamycin was isolated and determined using nuclear magnetic resonance (NMR) spectroscopic techniques. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and electrophoretic mobility shift assay (EMSA) were performed to investigate the mechanism underlying the activation effect on the anthrachamycin biosynthetic gene cluster. This work indicated that the rpoB-specific missense H437Y mutation had activated anthrachamycin biosynthesis in S. chattanoogensis L10. This may be helpful in the investigation of the pleiotropic regulation system in Streptomyces.
Responses of water accumulation and solute metabolism in tomato fruit to water scarcity and implications for main fruit quality variables

Abstract Fruit is important for human health, and applying deficit irrigation in fruit production is a strategy to regulate fruit quality and support environmental sustainability. Responses of different fruit quality variables to deficit irrigation have been widely documented, and much progress has been made in understanding the mechanisms of these responses. We review the effects of water shortage on fruit water accumulation considering water transport from the parent plant into the fruit determined by hydraulic properties of the pathway (including xylem water transport and transmembrane water transport regulated by aquaporins) and the driving force for water movement. We discuss water relations and solute metabolism that affect the main fruit quality variables (e.g. size, flavour, nutrition, and firmness) at the cellular level under water shortage. We also summarize the most recent advances in the understanding of responses of the main fruit quality variables to water shortage, considering the effects of variety, the severity of water deficit imposed, and the developmental stage of the fruit. We finally identify knowledge gaps and suggest avenues for future research. This review provides new insights into the stress physiology of fleshy fruit, which will be beneficial for the sustainable production of high-quality fruit under deficit irrigation.
Examining the ecological validity of the prototype willingness model for adolescent and young adult alcohol use.

The present study is the first ecologically valid, daily level test of the prototype willingness model (PWM), a model previously tested with hypothetical scenarios to investigate the social reaction and reasoned pathways toward engaging in health-risk behavior. The purpose of the present study is to examine whether days with elevated alcohol-favorable PWM cognitions are also associated with greater intentions and willingness to drink and increased drinking behavior on that day. Participants included 15-25-year-olds (N = 124; 57.3% female; Mage =18.7; SD = 2.87) who were part of an ecological momentary assessment study on drinking cognitions (including willingness, intentions, perceived vulnerability, social norms, prototype favorability) and alcohol use, reported across 3 weeks. Analyses accounted for the multilevel structure of the data and the various outcome distributions. Findings supported and advanced the PWM by using real-time, real-world daily data that captured within-person variation of PWM cognitions across days and showed daily level associations between PWM cognitions and alcohol use and negative consequences among adolescents and young adults, thus supporting the social reaction and reasoned pathways at the daily level. Current results may improve interventions by precisely informing the use of technology to bring interventions to adolescents and young adults in moments when they are at highest risk (i.e., days with higher than usual PMW alcohol cognitions). (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Early Intervention and Sustaining the Management of Vulnerability

Objective: The purpose of this article is to consider the issue of how long early intervention needs to be sustained to have a long-term impact on the course of psychosis. Method: Factors relevant to the concept of secondary prevention in psychosis are discussed. The need for sustained intervention for long-term impact on psychosis is examined. Evidence concerning the length of time required for the maximal impact of early intervention services and interventions that have been demonstrated as effective in achieving long-term change is reviewed. Thearticle discusses individuals of low and high vulnerability to schizophrenia and the interaction between this vulnerability and the length and type of treatment they require to change the deteriorating course of psychosis. Results: There is increasing evidence for the concept of a 'critical period' lasting up to 5 years after first presentation, during which the long-term level of vulnerability to relapse and disability may be determined. Conclusions: For manyhighly vulnerable patients, early intervention must be sustained for a minimum of 3 years to prevent or limit the potential for early decline. A core unanswered question is whether effective early intervention prevents potential long-term disability or merely delays it.
Operant Conditioning of Schizophrenic Children *

Since the early descriptions by Kanner (34), Bender (10) and Mahler (41), childhood schizophrenia has 'become an increasingly fascinating area of investi­ gation. Though there have been many studies, there are few facts on which investigators can agree. There is little agreement regarding the disease entity, though nine descriptive points are gain­ ing greater acceptance (14) as a basis for diagnosis. The incidence and prevalance is not known (56) though there is an apparent increase with increasing awareness of the symptomatology (12). Most investigators would agree chat there is an underlying ego or develop­ mental dysfunction, but the etiology is still hotly debated (49). The one fact on which they do agree is that treatment has been uniformly unsuccessful (15, 9, 27). Eisenburg (18) stated that there "appears to be little if any correlation between formal psychiatric treatment and clinical outcome. "
Evaluation of temporomandibular disorders and oral health-related quality of life with obese patients

ABSTRACT Objective: The aim of this study was to investigate the relationship between temporomandibular disorders and oral health impact profile in healthy, overweight, and obese patients. Methods: This study was carried out on 1528 individuals divided into three groups as healthy, overweight, and obese patients. Diagnostic Criteria for Temporomandibular Disorders, Fonseca’s questionnaire, and Oral Health Impact Profile-14 (OHIP-14) forms were used. Results: Gender, classification, pain, temporomandibular joint noise, and open-lock of the jaw of healthy, overweight, and obese groups were found to be related. The differences in the Fonseca and the OHIP-14 total scores according to the groups were found to be statistically significant. The correlation between the Fonseca total score and age was positive and significant. Conclusion: In the obese patients, both total Fonseca and OHIP-14 values were found to be higher. Also, the presence of pain in the obese patients was found to be higher.
Asymmetric Total Synthesis of (-)-Pavidolide B via a Thiyl-Radical-Mediated [3+2] Annulation Reaction.

The development of an efficient strategy for the asymmetric total synthesis of the bioactive marine natural product (-)-pavidolide B is described in detail. The development process and detours leading to the key thiyl-radical-mediated [3+2] annulation reaction, which constructed the central C ring with 4 contiguous stereogenic centers in one step, is depicted. Subsequently, the seven-membered D ring is constructed via a ring-closing metathesis reaction followed by a Rh(III)-catalyzed isomerization. This strategy enables the total synthesis of (-)-pavidolide B in a longest linear sequence of 10 steps.
Epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus isolates colonizing pigs with different exposure to antibiotics

Background In 2016, very high rates of methicillin-resistant Staphylococcus aureus (MRSA)-ST398 (99%) were found in Portuguese pig farms that used colistin, amoxicillin, and zinc oxide as feed additives. Since then, farms A and B banned the use of colistin, and farm C banned the use of both antibiotics. Objective The aim of the present study was to evaluate the impact of the ban of colistin and amoxicillin on pig MRSA carriage rates, clonal types and antimicrobial resistance, compared to the results obtained in 2016. Methods In 2018, 103 pigs (52 from farm B using amoxicillin only as a feed additive and 51 from farm C where no antibiotics were included in the feed regimen) were nasally swabbed for MRSA colonization. Isolates were tested for antimicrobial susceptibility, and characterised by spa typing, SCCmec typing and MLST. Whole genome sequencing (WGS) was performed for representative isolates. Results Overall, 96% of the pigs swabbed in 2018 carried MRSA, mostly ST398-SCCmec V-spa types t011/t108. MRSA from pigs not receiving antibiotics in the feed regimen showed susceptibility to a higher number of antibiotics, namely erythromycin, ciprofloxacin, gentamicin, and chloramphenicol. Notably, most of these isolates (n = 52) presented an unusual erythromycin-susceptibility/clindamycin-resistance phenotype. WGS showed that these isolates lacked the erm and the lnu genes encoding resistance to macrolides and lincosamides, respectively, but carried the vgaALC gene encoding resistance to lincosamides, which is here firstly identified in S. aureus ST398. Conclusion After two years the ban of colistin and amoxicillin as feed additives had no significant impact on the MRSA nasal carriage rates. Nevertheless, the MRSA strains circulating in those farms showed resistance to a lower number of antibiotic classes.
Benzodioxane‐Benzamides as Antibacterial Agents: Computational and SAR Studies to Evaluate the Influence of the 7‐Substitution in FtsZ Interaction

FtsZ is a crucial prokaryotic protein involved in bacterial cell replication. It recently arose as a promising target in the search for antimicrobial agents able to fight antimicrobial resistance. In this work, going on with our structure‐activity relationship (SAR) study, we developed variously 7‐substituted 1,4‐benzodioxane compounds, linked to the 2,6‐difluorobenzamide by a methylenoxy bridge. Compounds exhibit promising antibacterial activities not only against multidrug‐resistant Staphylococcus aureus, but also on mutated Escherichia coli strains, thus enlarging their spectrum of action toward Gram‐negative bacteria as well. Computational studies elucidated, through a validated FtsZ binding protocol, the structural features of new promising derivatives as FtsZ inhibitors.
Clinical determinants of social media use in individuals with schizophrenia

This study aimed to examine the prevalence of social media use and its association with symptoms in individuals with schizophrenia. 265 individuals with schizophrenia were assessed. Symptoms were assessed on the Positive and Negative Syndrome Scale (PANSS) and the Clinical Assessment Interview for Negative Symptoms (CAINS). Information on social media use was collected. Logistic regressions were used to explore the association between social media use and socio-demographic and clinical characteristics of the participants. Of the 265 study participants, 139 (52.5%) used social media in the last week. Fifty-six (21.1%) of the study participants used more than one social media site in the last week. Facebook was the most popular social media site. Age, highest education level, monthly household income, PANSS negative and depression factor scores were significantly associated with social media use. Amongst negative symptoms, the CAINS motivation-pleasure (MAP) social factor scores were found to be significantly associated with social media use. Our study results suggested that the assessment of social interactions via social media should be considered in the clinical assessment of individuals with schizophrenia. Secondly, our results suggested that the development of treatment programs supported by social media platforms may be useful for certain groups of individuals with schizophrenia. Younger patients with above secondary level education, higher family income and lower symptom severity are likely to be avid users of social media and would be suitable candidates to receive illness related information or clinical interventions via social media.
A Molecular Mechanism Underlying Genotype‐Specific Intrahepatic Cholestasis Resulting From MYO5B Mutations

Progressive familial intrahepatic cholestasis (PFIC) 6 has been associated with missense but not biallelic nonsense or frameshift mutations in MYO5B, encoding the motor protein myosin Vb (myoVb). This genotype‐phenotype correlation and the mechanism through which MYO5B mutations give rise to PFIC are not understood. The aim of this study was to determine whether the loss of myoVb or expression of patient‐specific myoVb mutants can be causally related to defects in canalicular protein localization and, if so, through which mechanism.