Miracle-dz/UniFAR-FTUs huggingface dataset:
The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics.

Background CYP2D6 and CYP2C19 enzymes are essential in the metabolism of antidepressants and antipsychotics. Genetic variation in these genes may increase risk of adverse drug reactions. Antidepressants and antipsychotics have previously been associated with risk of diabetes. We examined whether individual genetic differences in CYP2D6 and CYP2C19 contribute to these effects. Methods We identified 31,579 individuals taking antidepressants and 2,699 taking antipsychotics within UK Biobank. Participants were classified as poor, intermediate or normal metabolisers of CYP2D6, and as poor, intermediate, normal, rapid and ultra-rapid metabolisers of CYP2C19. Risk of diabetes mellitus represented by HbA1c level was examined in relation to the metabolic phenotypes. We analysed drugs either individually (where sample size permitted) or grouped by class. Results CYP2D6 poor metabolisers taking paroxetine had higher Hb1Ac than normal metabolizers (mean difference: 2.29mmol/mol; p < 0.001). Among participants with diabetes who were taking venlafaxine, CYP2D6 poor metabolisers had higher HbA1c levels compared to normal metabolisers (mean differences: 10.15 mmol/mol; p < 0.001. Among participants with diabetes who were taking fluoxetine, we observe that CYP2D6 intermediate metabolisers and decreased HbA1c, compared to normal metabolisers (mean difference -7.74mmol/mol; p=0.017). We did not observe any relationship between CYP2D6 or CYP2C19 metabolic status and HbA1c levels in participants taking antipsychotic medication. Conclusion Our results indicate that the impact of genetic variation in CYP2D6 differs depending on diabetes status. Although our findings support existing clinical guidelines, further research is essential to inform pharmacogenetic testing for people taking antidepressants and antipsychotics.
Vaccine package inserts and prescribing habits of obstetricians-gynecologists for maternal vaccination

ABSTRACT Despite ample evidence of the safety and efficacy of the influenza vaccine and the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy, two-thirds of pregnant women do not receive these vaccines. Providers have a significant role in increasing prenatal vaccine uptake. It is important to understand how different sources of vaccine prescribing information, such as Food and Drug Administration package inserts, influence provider recommendations. We aimed to examine the role of vaccine package inserts in provider recommendations and perceptions of safety and effectiveness of vaccines during pregnancy. A cross-sectional survey was mailed to a random, weighted sample of American College of Obstetricians and Gynecologists Fellows living in the United States in March 2019. Providers were asked about their attitudes toward package inserts, and to evaluate sample package insert statements following two different labeling rules. Their evaluations of each rule were then compared. Of the 321 respondents, the majority (90%, 288/321) recommended and/or administered maternal vaccinations. Few respondents (7.8%, 25/321) read package inserts for information regarding vaccination. Respondents were less likely to recommend sample vaccines with Pregnancy and Lactation Labeling Rule-complying inserts (46.1%, 148/321) than vaccines with Pregnancy Category inserts (87.5%, 282/321). Although most providers did not actively utilize vaccine package inserts to inform recommendations, the previous Pregnancy Categories rule was preferred compared to the Pregnancy and Lactation Labeling Rule. Collaborative efforts to update inserts with current clinical practices for pregnancy would be valuable in reducing apprehensiveness around package inserts to generate safer and more cogent recommendations for pregnant women.
Sweetness is in the ear of the beholder: chord preference across United Kingdom and Pakistani listeners

The majority of research in the field of music perception has been conducted with Western participants, and it has remained unclear which aspects of music perception are culture dependent, and which are universal. The current study compared how participants unfamiliar with Western music (people from the Khowar and Kalash tribes native to Northwest Pakistan with minimal exposure to Western music) perceive affect (positive versus negative) in musical chords compared with United Kingdom (UK) listeners, as well as the overall preference for these chords. The stimuli consisted of four distinct chord types (major, minor, augmented, and chromatic) and were played as both vertical blocks (pitches presented concurrently) and arpeggios (pitches presented successively). The results suggest that the Western listener major‐positive minor‐negative affective distinction is opposite for Northwest Pakistani listeners, arguably because of the reversed prevalence of these chords in the two music cultures. The aversion to the harsh dissonance of the chromatic cluster is present cross‐culturally, but the preference for the consonance of the major triad varies between UK and Northwest Pakistani listeners, depending on cultural familiarity. Our findings imply not only notable cultural variation but also commonalities in chord perception across Western and non‐Western listeners.
Examining suicide assessment measures for research use: Using item response theory to optimize psychometric assessment for research on suicidal ideation in major depressive disorder.

INTRODUCTION Progress reducing suicide death will require randomized clinical trials (RCTs) specifically targeting suicide risk. Even large RCTs may not stipulate suicide death as the primary outcome, as suicide death is relatively uncommon. Therefore, RCTs may need to specify suicidal ideation as a proxy indicator of risk. There is no consensus on the best tool for measuring suicidal ideation within RCTs. We contrasted the psychometric performance of three suicidal ideation measures to address this need. METHODS We applied item response theory to the Beck Scale for Suicide Ideation (BSSI), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the suicide item of the Hamilton Rating Scale for Depression (HRSD) for 101 outpatients with depression and suicidal ideation participating in a RCT with suicidal ideation as the primary outcome. RESULTS All measures of suicidal ideation were equally able to detect low and very high levels of suicidal ideation. CONCLUSIONS The choice of the specific measure of suicidal ideation in a clinical trial may be dictated by time and financial resources versus the need for granularity in the interpretation of the scores.
Visual Performance of Two Diffractive Trifocal Intraocular Lenses: A Randomized Trial.

PURPOSE To compare two trifocal intraocular lenses (IOLs), the RayOne Trifocal RAO603F IOL (closed-loop haptic IOL; Rayner Intraocular Lenses Limited) and the AT Lisa tri 839 MP IOL (plate-haptic IOL; Carl Zeiss Meditec AG), concerning optical and capsular bag performance. METHODS Patients scheduled for cataract surgery received either a closed-loop haptic IOL or a plate-haptic IOL in the first eye and the other IOL in the second eye. Three months postoperatively, autorefraction and subjective refraction, uncorrected and corrected distance visual acuity at 4 m, 80 cm, and 40 cm, an objective reading test (Salzburg Reading Desk; SRD Vision), a defocus curve, IOL tilt and decentration, a questionnaire about dysphotopsia, and grading of halos with a halometer were performed. RESULTS Eighty-eight eyes of 44 patients were included. Visual acuity was comparable between both IOLs. The closed-loop haptic IOL performed better in the defocus curve at -1.50 diopters (D) (0.08 ± 0.10 vs 0.12 ± 0.09 logMAR; P < .01). The plate-haptic IOL had better contrast sensitivity without glare under mesopic and photopic conditions in miosis (P = .0018 and .002, respectively) and mydriasis (P = .017 and .003, respectively). Significant differences were found for less overall subjective disturbance (P = .047) and starbursts (P = .039) for the plate-haptic IOL, but not for the other positive dysphotopsia symptoms. CONCLUSIONS Both trifocal IOLs delivered good and comparable visual function with low degrees of disturbing dysphotopsia. The closed-loop haptic IOL was slightly superior in the defocus curve, whereas the plate-haptic IOL was slightly superior concerning contrast sensitivity and positive dysphotopsia. [J Refract Surg. 2021;37(7):460-465. ].
Synchronization of Complex Dynamical Networks Subject to DoS Attacks: An Improved Coding–Decoding Protocol

This article investigates the synchronization of communication-constrained complex dynamic networks subject to malicious attacks. An observer-based controller is designed by virtue of the bounded encode sequence derived from an improved coding–decoding communication protocol. Moreover, taking the security of data transmission into consideration, the denial-of-service attacks with the frequency and duration characterized by the average dwell-time constraint are introduced into data communication, and their influence on the coder string is analyzed explicitly. Thereafter, by imposing reasonable restrictions on the transmission protocol and the occurrence of attacks, the boundedness of coding intervals can be obtained. Since the precision of data is generally limited, it may lead to the situation that the signal to be encoded overflows the coding interval such that it results in the unavailability of the developed coding scheme. To cope with this problem, a dynamic variable is introduced to the design of the protocol. Subsequently, based on the Lyapunov stability theory, sufficient conditions for ensuring the input-to-state stability of the synchronization error systems under the communication-constrained condition and malicious attacks are presented. The validity of the developed method is finally verified by a simulation example of chaotic networks.
Intra-amniotic infection and sterile intra-amniotic inflammation in women with preterm labor with intact membranes are associated with a higher rate of Ureaplasma species DNA presence in the cervical fluid

Abstract Objective To determine the prevalence of Ureaplasma spp. DNA and its load in the cervical fluid in women with preterm labor with intact membranes (PTL) complicated by intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation) or sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation alone). Methods Overall, 115 women with singleton pregnancies complicated by PTL between gestational ages of 22 + 0 and 34 + 6 weeks were included in this study. Paired amniotic and cervical fluid samples were collected at the time of admission via transabdominal amniocentesis using a Dacron polyester swab. Microbial invasion of the amniotic cavity was diagnosed based on a combination of culture and molecular biology methods. Intra-amniotic inflammation was determined based on the concentration of interleukin-6 in the amniotic fluid. Bacterial and Ureaplasma spp. DNA loads were assessed in the cervical fluid using PCR. Results Intra-amniotic infection and sterile inflammation were identified in 14% (16/115) and 25% (29/115) of the women, respectively. Ureaplasma spp. DNA in the cervical fluid was identified in 51% (59/115) of women. The presence of Ureaplasma spp. DNA in the cervical fluid was higher in women with intra-amniotic infection (75% (12/16)) and sterile intra-amniotic inflammation (76% (22/29)) than in women without intra-amniotic inflammation (36% (25/70); p = . 0002). Concurrent presence of Ureaplasma spp. and Mycoplasma hominis DNA was higher in women with intra-amniotic infection (42% (5/12)) than women with sterile intra-amniotic inflammation (7% (2/29)) and women without intra-amniotic inflammation (7% (5/70); p = . 001). There were no differences in the load of Ureaplasma spp. DNA in the cervical fluid among women with intra-amniotic infection, sterile intra-amniotic inflammation, and those without intra-amniotic inflammation (median values; infection: 1.2 × 104 copies DNA/mL; sterile: 5.0 × 105 copies DNA/mL; without: 8.4 × 104 copies DNA/mL; p = .18). Conclusions In PTL , both forms of intra-amniotic inflammation were associated with a higher prevalence of Ureaplasma spp. DNA in the cervical fluid. The presence of intra-amniotic infection was related to a higher rate of concurrent Ureaplasma spp. and M. hominis DNA in the cervical fluid.
Metabolic derangements are associated with impaired glucose delivery following traumatic brain injury

Abstract Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited. Eighteen volunteers were excluded for age over 60 years (n = 11), movement-related artefact (n = 3) or physiological instability during imaging (n = 4). We measured cerebral blood flow, blood volume, oxygen extraction fraction, and 18F-FDG transport into the brain (K1) and its phosphorylation (k3). We calculated oxygen metabolism, 18F-FDG influx rate constant (Ki), glucose metabolism and the oxygen/glucose metabolic ratio. Lesion core, penumbra and peri-penumbra, and normal-appearing brain, ischaemic brain volume and k3 hotspot regions were compared with plasma and microdialysis glucose in patients. Twenty-six head injury patients, median age 40 years (22 male, four female) underwent 34 combined 18F-FDG and oxygen-15 PET at early, intermediate, and late time points (within 24 h, Days 2–5, and Days 6–12 post-injury; n = 12, 8, and 14, respectively), and were compared with 20 volunteers, median age 43 years (15 male, five female) who underwent oxygen-15, and nine volunteers, median age 56 years (three male, six female) who underwent 18F-FDG PET. Higher plasma glucose was associated with higher microdialysate glucose. Blood flow and K1 were decreased in the vicinity of lesions, and closely related when blood flow was <25 ml/100 ml/min. Within normal-appearing brain, K1 was maintained despite lower blood flow than volunteers. Glucose utilization was globally reduced in comparison with volunteers (P < 0.001). k3 was variable; highest within lesions with some patients showing increases with blood flow <25 ml/100 ml/min, but falling steeply with blood flow lower than 12 ml/100 ml/min. k3 hotspots were found distant from lesions, with k3 increases associated with lower plasma glucose (Rho −0.33, P < 0.001) and microdialysis glucose (Rho −0.73, P = 0.02). k3 hotspots showed similar K1 and glucose metabolism to volunteers despite lower blood flow and oxygen metabolism (P < 0.001, both comparisons); oxygen extraction fraction increases consistent with ischaemia were uncommon. We show that glucose delivery was dependent on plasma glucose and cerebral blood flow. Overall glucose utilization was low, but regional increases were associated with reductions in glucose availability, blood flow and oxygen metabolism in the absence of ischaemia. Clinical management should optimize blood flow and glucose delivery and could explore the use of alternative energy substrates.
Prevalence of malnutrition/malnutrition risk and nutrition-related risk factors among patients with Parkinson’s disease: systematic review and meta-analysis

ABSTRACT Introduction The clinical symptoms and nutritional status of patients with Parkinson's disease (PwP) are interrelated, and the clinical outcomes in malnourished patients are often poor. Only a few studies have reviewed the prevalence of malnutrition and nutrition-related risk factors in PwP. Objective To explore the prevalence of malnutrition/ malnutrition risk among PwP, and estimate nutrition-related risk factors. Methods PubMed, EMBASE, and Cochrane Library were systematically searched. Literatures published between 1 January 1995 and 1 November 2020, subjects were patients with idiopathic PD underwent Mini Nutritional Assessment (MNA) were included. Result Sixteen articles, including 1650 PwP from 13 countries/regions, were included in the meta-analysis. The prevalence of malnutrition and malnutrition risk were 8.8% (Confidence interval [CI] 95%, 5.3%–12.2%) and 35.3% (CI 95%, 29.0%–41.7%), and the prevalence of nutritional disorders was 42.3% (CI 95%, 33.7%–51%). The prevalence of malnutrition in developing countries was higher than that in the developed countries. Meta-analysis reveals there were significant differences in the course of the disease (0.88 years; 95% CI, 0.26–1.50), levodopa equivalent daily dose (LEDD; 60.77 mg/day; 95% CI, 2.7–118.8), Hoehn and Yahr (H&Y) staging (0.323; CI 95%, 0.164–0.482), and unified Parkinson's disease rating scale (UPDRS) scores (total: 13.66, CI 95%: 10.57–16.75 and part III: 5.52, CI 95%: 3.79–7.25) between normal and nutritional disorder groups. Conclusions Malnutrition/malnutrition risk prevalence in PwP are high. The duration of the disease, LEDD, H&Y staging, and UPDRS score (part III and total) may be nutrition-related risk factors in PwP.
Impact of dermal matrix thickness on split‐thickness skin graft survival and wound contraction in a single‐stage procedure

Optimal treatment of full‐thickness skin injuries requires dermal and epidermal replacement. To spare donor dermis, dermal substitutes can be used ahead of split‐thickness skin graft (STSG) application. However, this two‐stage procedure requires an additional general anaesthetic, often prolongs hospitalisation, and increases outpatient services. Although a few case series have described successful single‐stage reconstructions, with application of both STSG and dermal substitute at the index operation, we have little understanding of how the physical characteristics of dermal substitutes affects the success of a single‐stage procedure. Here, we evaluated several dermal substitutes to optimise single‐stage skin replacement in a preclinical porcine model. A porcine full‐thickness excisional wound model was used to evaluate the following dermal substitutes: autologous dermal graft (ADG; thicknesses 0.15‐0.60 mm), Integra (0.4‐0.8 mm), Alloderm (0.9‐1.6 mm), and chitosan‐based hydrogel (0.1‐0.2 mm). After excision, each wound was treated with either a dermal substitute followed by STSG or STSG alone (control). Endpoints included graft take at postoperative days (PODs) 7 and 14, wound closure at POD 28, and wound contracture from POD 28‐120. Graft take was highest in the STSG alone and hydrogel groups at POD 14 (86.9% ± 19.5% and 81.3% ± 12.3%, respectively; P < .001). There were no differences in graft take at POD 7 or in wound closure at POD 28, though highest rates of wound closure were seen in the STSG alone and hydrogel groups (93.6% ± 9.1% and 99.8% ± 0.5%, respectively). ADG‐treated wounds demonstrated the least amount of wound contracture at each time point. Increase dermal substitute thickness was associated with worse percent graft take at PODs 14 and 28 (Spearman ρ of −0.50 and −0.45, respectively; P < .001). In this preclinical single‐stage skin reconstruction model, thinner ADG and hydrogel dermal substitutes outperformed thicker dermal substitutes. Both substitute thickness and composition affect treatment success. Further preclinical and clinical studies to optimise this treatment modality are warranted.
Impact of patients’ attitudes and dynamics in needs and life experiences during their journey in COPD: an ethnographic study

ABSTRACT Objectives Despite its importance in determining coping behaviors, few studies have assessed the reality of chronic obstructive pulmonary disease (COPD) and its management perceived by patients. This study aimed at an in-depth understanding of this reality to identify COPD patients’ attitudes, COPD-shaped experiences, and overlooked needs during their journey. Methods Qualitative ethnographic study including 28 adult patients with moderate and severe COPD and 20 healthcare professionals. Study phases were (1) in-depth individual and (2) ethnographic interviews (qualitative), and (3) online questionnaires (quantitative), including 400 patients. Qualitative data were collected using audio, video, and observation notes. Three ethnographers analyzed data using a template covering different themes: attitudes of COPD patients, COPD-shaped experiences, and overlooked needs. Results We identified four attitudinal profiles of COPD patients: ‘active controller,’ ‘naïve minimizer,’ ‘defeated sufferer,’ and ‘struggling bon vivant,’ which were validated in 400 COPD patients, as well as five stages in the COPD patient journey and overlookedneeds. The ‘active controller’ profile was associated with slower disease progression compared with the ‘defeated sufferer’ and ‘struggling bon vivant’ profiles. Conclusion Four attitudinal profiles were distinguished and validated in a large sample of COPD patients. Patients’ attitudes impacted in COPD-associated experiences, limitations, and unmet needs, which differed among profiles.
Clinical and molecular findings in patients with pattern dystrophy

ABSTRACT Purposes: To study the clinical and genetic background of a series of Italian patients affected by pattern dystrophy (PD). Methods: We reviewed patients with a clinical diagnosis of PD examined at the Eye Clinic in Florence from 2012 to 2019. We took into consideration patients with a standard ophthalmological examination, personal and familial ophthalmological history, fundus imaging, and molecular genetic analysis of genes PRPH2 and BEST1. We labelled patients with BEST1 and PRPH2 mutations as m-PD group (mutated) whereas patients with no mutations in these 2 genes as nm-PD group (non-mutated). Results: Seventy-seven PD patients were assessed (average age 59.7 ± 14.2, range 31–88 years). Fifty patients were placed in the nm-PD group and 27 in the m-PD. Pathogenic BEST1 and PRPH2 mutations were detected in 7% and 22% of PD patients, respectively. In total, we reported 1 BEST1 and 8 PRPH2 novel mutations. Ten patients were characterized by drusen in the nm-PD group whereas in no patients in the m-PD group drusen were detected at the fundus. Conclusions: An important proportion of patients affected by PD showed BEST1 or PRPH2 mutations. Patients affected by drusen represent a different sub-phenotype. Genetic examination is recommended for a correct clinical management.
Assessment of Liaison XL Murex Chagas diagnostic performance in blood screening for Chagas disease using a reference array of chimeric antigens

Chagas disease (CD) serological screening at blood banks is usually performed by a single highly sensitive serological assay, with chemiluminescent immunoassays (CLIAs) being the method of choice. CLIAs employ recombinant, fusion peptides and/or chimeric antigens that selectively capture anti‐Trypanosoma cruzi antibodies. However, despite high sensitivity, the ability of these tests to identify CD‐positive cases should be evaluated against T. cruzi strains circulating in specific locales. Herein, we used a latent class analysis (LCA) approach employing an array of four chimeric antigens to assess the diagnostic performance of the Liaison XL Murex Chagas CLIA for the detection of anti‐T. cruzi IgG in serum samples.