Miracle-dz/UniFAR-FTUs huggingface dataset:
Mental Health Burden of the COVID-19 Outbreak in Germany: Predictors of Mental Health Impairment

Introduction: COVID-19 is causing an enormous psychological burden for most people. This study aims to assess individual changes in mental health and health status before and after the COVID-19 outbreak, and to explore potential predictors of change. Methods: A cross-sectional study in Germany (n = 15 037) were conducted. Demographics, depression and anxiety symptoms (PHQ-2, GAD-2), distress (DT), and health status (EQ-5D-3L) were assessed. Additionally, all instruments used were adapted to measure the participants’ mental health and health status before the COVID-19 outbreak. COVID-19-related fear, trust in governmental actions to face COVID-19, and the subjective level of information about COVID-19 were examined. Results: Overall, the participants showed a significant increase in depression and anxiety symptoms, and distress, while health status deteriorated since the COVID-19 outbreak. Impairment in mental health was predicted by COVID-19-related fear. Pre-existing mental illness predicted an increase in depression symptoms and a deterioration in health status. Trust in governmental actions and the subjective level of information predicted less increase in psychological burden. Conclusions: Our data revealed that there have been changes in mental health and health status at an individual level since the outbreak of COVID-19. In order to maintain mental health, the observed predictors should be addressed.
In vitro reconstitution and characterization of pyruvate dehydrogenase and 2‐oxoglutarate dehydrogenase hybrid complex from Corynebacterium glutamicum

Pyruvate dehydrogenase (PDH) and 2‐oxoglutarate dehydrogenase (ODH) are critical enzymes in central carbon metabolism. In Corynebacterium glutamicum, an unusual hybrid complex consisting of CgE1p (thiamine diphosphate‐dependent pyruvate dehydrogenase, AceE), CgE2 (dihydrolipoamide acetyltransferase, AceF), CgE3 (dihydrolipoamide dehydrogenase, Lpd), and CgE1o (thiamine diphosphate‐dependent 2‐oxoglutarate dehydrogenase, OdhA) has been suggested. Here, we elucidated that the PDH‐ODH hybrid complex in C. glutamicum probably consists of six copies of CgE2 in its core, which is rather compact compared with PDH and ODH in other microorganisms that have twenty‐four copies of E2. We found that CgE2 formed a stable complex with CgE3 (CgE2‐E3 subcomplex) in vitro, hypothetically comprised of two CgE2 trimers and four CgE3 dimers. We also found that CgE1o exists mainly as a hexamer in solution and is ready to form an active ODH complex when mixed with the CgE2‐E3 subcomplex. Our in vitro reconstituted system showed CgE1p‐ and CgE1o‐dependent inhibition of ODH and PDH, respectively, actively supporting the formation of the hybrid complex, in which both CgE1p and CgE1o associate with a single CgE2‐E3. In gel filtration chromatography, all the subunits of CgODH were eluted in the same fraction, whereas CgE1p was eluted separately from CgE2‐E3, suggesting a weak association of CgE1p with CgE2 compared with that of CgE1o. This study revealed the unique molecular architecture of the hybrid complex from C. glutamicum and the compact‐sized complex would provide an advantage to determine the whole structure of the unusual hybrid complex.
Effectiveness and safety of switching from originator to biosimilar adalimumab in patients with psoriasis

Dear Editor, Real-life data regarding the effectiveness and safety of switching from an originator to a biosimilar drug for treatment of psoriasis are still lacking. We present data from psoriasis patients who were administratively switched from originator adalimumab (Humira is manufactured by AbbVie) to the biosimilar Hyrimoz (Hyrimoz is manufactured by Sandoz) from 1 November 2018 to 21 January 2019 at a tertiary dermatological care center, University Hospital Bispebjerg, Copenhagen, Denmark. Data were obtained through a questionnaire and electronic patient files accessed through the registry DERMBIO (www.dermbio. dk), which covers all dermatological patients with psoriasis who have been treated with biologics in Denmark. The questionnaire was administered 3 months after switching from originator to biosimilar with questions on patients' evaluation of treatment effect, Dermatology Life Quality Index (DLQI) and adverse events. A total of 43 patients were switched from Humira to Hyrimoz. Mean age was 53 years (min-max: 25-77), 62.9% were men (n = 27), the patients had received Humira for 6.3 years on average (SD 3.1) and 25.6% (n = 11) had received another biologic drug prior to adalimumab. Twenty-seven and four patients (n = 31, 72.1%) reported same or better effect, respectively, after switching, whereas 12 (27.9%) reported worse effect. After switching to the biosimilar, overall mean score in Psoriasis Area and Severity Index (PASI) and DLQI increased with 0.21 points (CI: −0.32 to 0.76, P = .42) and 1.09 points (CI: −0.46 to 2.63, P = .16), respectively (Table 1). Although no significant difference in effectiveness based on PASI scoring and DLQI questionnaire could be detected after switching from originator to biosimilar, the differences in mean for PASI and DLQI were significantly lower in patients who reported same or better effect, −1.51 points (CI: 0.37-2.65, P = .01) and −3.62 points (CI: 0.27-6.98, P = .04), respectively, when compared to patients reporting worse effect. After switching, the fraction of patients with a PASI score of 0 decreased from 63.2% to 55.3% (P = .63), whereas the fraction of patients with a DLQI score ≤1 decreased from 74.3% to 62.9% (P = .34). Change in PASI after switching was correlated to change in DLQI (r = .77, P < 0.001). In a linear regression model with change in DLQI as outcome measure, we found a significant interaction between change in PASI score and self-reported effect, meaning that patients who reported a worse subjective effect of the treatment after
Effects of pH, Temperature, Ethanol, and Malate Concentration onLactobacillus plantarumandLeuconostoc oenos:Modelling of the Malolactic Activity

The effects of several chemico-physical factors (pH, SO2, and ethanol concentration) on the growth and malolactic activity of Lactobacillus plantarum and Leuconostoc oenos strains, isolated from different Italian red wines, were evaluated. A large individual variability of stress resistance was observed within the two species. The isolates of L. plantarum showed, under the various conditions better growth performances with respect to Leuc. oenos. Ethanol and malic acid concentration, temperature, pH, and inoculum size were modulated according a Central Composite Design (CCD). Two representative strains of each of the two species were individually grown in the various combinations of the CCD, and their activity was evaluated by gas chromatograph on the basis of the CO2 concentration in the head space of sealed vials. The malolactic activity of the various runs were modelled according to the Gompertz equation. The Gompertz parameters, µmax and length of lag phase, were calculated in order to obtain polynomial equations. The comparison of the models obtained indicated that different factors limit the activities of the two species and that L. plantarum is more resistant to the combined action of various stresses. Having revealed a weaker dependence on the medium modifications as well as higher decarboxylation performances, L. plantarum can be considered as a more efficient alternative to Leuc. oenos for the induction of malolactic fermentation in musts.
Distribución geográfica y hábitat de la familia Trochillidae (Aves)en el estado de Guerrero, México

Geographical distribution and habitat of Trochilidae (Aves) in the state of Guerrero, Mexico. The distribution and abundance of species of Trochillidae family is usually influenced by the flowering and phenology of plants used as a feeding source, mainly in primary forest, so that changes in vegetation cover could impact their populations. We analyzed and characterized the geographical distribution and habitat for 22 species of resident hummingbirds in the state of Guerrero using the vegetation and the land use map of INEGI Series IV (2007-2010). Distribution models were generated with the Genetic Algorithm for Rule Set Production (GARP), using historical records of scientific collections and fieldwork (2001-2009), in combination with climatic and topographic variables. Of the 22 modeled species, six are endemic to Mexico, the same number of species found in a risk category. The highest concentration with regards to richness (14-20 species), endemism (5-6 species) and number of threatened species of hummingbirds (5-6 species) occurred in the biotic province of Sierra Madre del Sur. However, the potential distribution of most of the hummingbirds occurred in disturbed sites or agroecosystems, as a result of changes in land-use. For Campylopterus hemileucurus, Lamprolaima rhami and Heliomaster longisrostris, their potential distribution was highest in areas of primary vegetation. Areas of high hummingbirds presence do not coincide with the Important Bird Areas proposed for bird conservation in Guerrero, considering that, despite its diversity and its extreme popularity, from the conservation perspective hummingbirds have received relatively little attention. Rev. Biol. Trop. 64 (1): 363-376. Epub 2016 March 01.
Worsening Baroreflex Sensitivity on Progression to Type II Diabetes: Localized vs. Systemic Inflammation and Role of Antidiabetic Therapy.

Cardiac autonomic neuropathy (CAN) is an early cardiovascular manifestation of type 2 diabetes (T2D) that constitutes an independent risk factor for cardiovascular mortality and morbidity. Nevertheless, its underlying pathophysiology remains poorly understood. We recently showed that localized perivascular adipose tissue (PVAT) inflammation underlies the incidence of parasympathetic CAN in prediabetes. Here, we extend our investigation to provide a mechanistic framework for the evolution of autonomic impairment as the metabolic insult worsens. Early metabolic dysfunction was induced in rats fed a mild hypercaloric diet. Two low-dose streptozotocin injections were used to evoke a state of late decompensated T2D. Cardiac autonomic function was assessed by invasive measurement of baroreflex sensitivity using the vasoactive method. Progression into T2D was associated with aggravation of CAN to include both sympathetic and parasympathetic arms. Unlike prediabetic rats, T2D rats showed markers of brainstem neuronal injury and inflammation as well as increased serum levels of IL-1b. Experiments on PC12 cells differentiated into sympathetic-like neurons demonstrated that brainstem injury observed in T2D rats resulted from exposure to possible pro-inflammatory mediators in rat serum rather than a direct effect of the altered metabolic profile. CAN and the associated cardiovascular damage in T2D only responded to combined treatment with insulin to manage hyperglycemia in addition to a non-hypoglycemic dose of metformin or pioglitazone providing an anti-inflammatory effect, coincident with the effect of these combinations on serum IL-1b. Our present results indicate that CAN worsening upon progression to T2D involves brainstem inflammatory changes likely triggered by systemic inflammation.
Clinical efficacy of anesthesia with intensive care nursing in attenuating postoperative complications in patients with breast cancer

Objective Complications frequently occur in patients with breast cancer after surgery. Anesthesia nursing plays an important role in decreasing complications for such patients. Thus, this study investigated the effects of anesthesia with intensive care nursing (AICN) on complication rates in patients with breast cancer after surgery. Methods Eighty-two patients with breast cancer were recruited in this study. Complications were compared between the anesthesia with usual nursing care (AUCN) and AICN groups. Results The results demonstrated that AICN decreased the rates of incision infection, drug extravasation, and catheter exposure, as well as pain and inflammation scores, compared with the findings in the AUCN group. AICN improved the time to orientation and decreased the incidence of nausea, anxiety, depression, and vomiting versus AUCN. In addition, AICN shortened the time to awakening after anesthesia compared with the effects of AUCN. Furthermore, AICN shortened hospital stay and increased survival rates. Notably, AICN improved health-related quality of life as measured using the EORTC QLQ-C30 questionnaire. Conclusion AICN provided more benefits and better postoperative outcomes than AUCN, suggesting its utility for minimizing complications in patients with breast cancer after surgery.
OPtical Coherence Tomography Guided Coronary Stent IMplantation Compared to Angiography: A Multicenter Randomized TriaL in PCI - Design and Rationale of ILUMIEN IV: OPTIMAL PCI.

AIMS Randomized trials have demonstrated improvement in clinical outcomes with intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI. The ILUMIEN III trial demonstrated non-inferiority of an optical coherence tomography (OCT)- versus IVUS-guided PCI strategy in achieving similar post-PCI lumen dimensions. ILUMIEN IV is a large-scale, multicenter, randomized trial designed to demonstrate the superiority of OCT- versus angiography-guided stent implantation in patients with high-risk clinical characteristics (diabetes) and/or complex angiographic lesions in achieving larger post-PCI lumen dimensions and improving clinical outcomes. METHODS AND RESULTS ILUMIEN IV is a prospective, single-blind clinical investigation that will randomize between 2490 and 3656 patients using an adaptive design to OCT-guided versus angiography-guided coronary stent implantation in a 1:1 ratio. The primary endpoints are: (1) Post-PCI minimal stent area assessed by OCT in each randomized arm, and (2) target vessel failure, the composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target vessel revascularization. Clinical follow-up will continue for up to 2 years. The trial is currently enrolling, and the principal results are expected in 2022. CONCLUSIONS The large-scale ILUMIEN IV randomized controlled trial will evaluate the effectiveness of OCT-guided versus angiography-guided PCI in improving post-PCI lumen dimensions and clinical outcomes in patients with diabetes and/or with complex coronary lesions.
Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia.

BACKGROUND Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known. METHODS We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24. RESULTS A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was -44.5% in the evolocumab group and -6.2% in the placebo group, for a difference of -38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was -77.5 mg per deciliter (-2.0 mmol per liter) in the evolocumab group and -9.0 mg per deciliter (-0.2 mmol per liter) in the placebo group, for a difference of -68.6 mg per deciliter (-1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. CONCLUSIONS In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. (Funded by Amgen; HAUSER-RCT ClinicalTrials.gov number, NCT02392559.).
The effects of acute and chronic exposure to 900 MHz radiofrequency radiation on auditory brainstem response in adult rats

ABSTRACT The aim of this study was to determine the effects of short and long-term RFR exposure on ABR by evaluating lipid peroxidation and antioxidant status in adult rats. Sixty male albino Wistar rats were randomly divided into four groups. S1:1 week sham, S10:10 weeks sham, E1:1 week RFR, E10:10 weeks RFR. Experimental group rats were exposed to RFR 2 h/day, 5 days/week during the test period. Sham rats were kept in the same conditions without RFR. After the experiment, ABRs were recorded from the mastoids of rats using tone burst acoustic stimuli. Biochemical investigations in rat brain and ultrastructural analysis in temporal cortex were performed. ABR wave I latency prolonged in E1-group and shortened in E10-group compared to their shams. TBARS level increased in E1-group, decreased in E10-group, on the contrary, SOD and CAT activities and GSH level decreased in E1-group, increased in E10-group compared to their sham groups. Edema was present in the neuron and astrocyte cytoplasms and astrocyte end-feet in both E1 and E10 groups. Our results suggest that 900 MHz RFR may have negative effects on the auditory system in acute exposure and no adverse effects in chronic exposure without weekends.
Spectroscopy integration to miniature bioreactors and large scale production bioreactors–Increasing current capabilities and model transfer

Spectroscopy techniques are being implemented within the biopharmaceutical industry due to their non‐destructive ability to measure multiple analytes simultaneously, however, minimal work has been applied focussing on their application at small scale. Miniature bioreactor systems are being applied across the industry for cell line development as they offer a high‐throughput solution for screening and process optimization. The application of small volume, high‐throughput, automated analyses to miniature bioreactors has the potential to significantly augment the type and quality of data from these systems and enhance alignment with large‐scale bioreactors. Here, we present an evaluation of 1. a prototype that fully integrates spectroscopy to a miniature bioreactor system (ambr®15, Sartorius Stedim Biotech) enabling automated Raman spectra acquisition, 2. In 50 L single‐use bioreactor bag (SUB) prototype with an integrated spectral window. OPLS models were developed demonstrating good accuracy for multiple analytes at both scales. Furthermore, the 50 L SUB prototype enabled on‐line monitoring without the need for sterilization of the probe prior to use and minimal light interference was observed. We also demonstrate the ability to build robust models due to induced changes that are hard and costly to perform at large scale and the potential of transferring these models across the scales. The implementation of this technology enables integration of spectroscopy at the small scale for better process understanding and generation of robust models over a large design space while facilitating model transfer throughout the scales enabling continuity throughout process development and utilization and transfer of ever‐increasing data generation from development to manufacturing.
PSYLLIDS AND THEIR MANAGEMENT

Psyllids are economically important as pests of several horticultural crops and also as biocontrol agents of weeds. Diaphorina citri, Apsylla cistellata and Heteropsylla cubana are the predominant psyllid pests in India. Asian citrus psylla, D. citri is one of the major threats to citrus cultivation not only as a pest but also as a vector of citrus greening, while A. cistellata is a gall inducer affecting panicle emergence in mango. Heteropsylla cubana infests Leucana leucocephala, an important fodder and agroforestry crop. Systemic insecticides like imidacloprid against D.citri and dimethoate against A. cistellata were reported effective. Bioagents of D.citri are Mallada boninensis, Cheilomenes sexmaculata and eulophid parasitoid, Tamarixia radiata while Curinus coerulus is an efficient predator of H.cubana. A brief account on these pests and management strategies are presented.
Natural history of achondroplasia: A retrospective review of longitudinal clinical data

There are limited data on the longitudinal frequency and severity of the symptoms and complications of achondroplasia. We undertook a retrospective electronic chart review of 114 patients to develop a more thorough understanding of the lifetime impact of achondroplasia. Craniocervical stenosis (involving the foramen magnum with or without cervical vertebrae C1 and/or C2) was noted in nearly 50% of patients with craniovertebral junction imaging; however, corrective decompression surgery was only needed in 6% of patients. No children in our cohort died at 4 years of age or under. Kyphosis was present in most patients but usually resolved in early childhood. Cervical and lumbar stenosis were diagnosed in children and adults while, genu varum, elbow contractures, and radial head dislocations were identified during childhood. Central sleep apnea and obstructive sleep apnea were present in children, while the diagnosis of obstructive sleep apnea was shown to recur in adulthood. Cardiovascular risk factors were present in only 7% of patients. A range of mental health disorders were identified, with most diagnoses being made before 18 years of age. Our data show that achondroplasia has a significant impact on patients' physical health, and complications continue to be reported and require intervention throughout patients' lifetimes. This highlights the need for continuous support beyond pediatric care, by adult care clinicians experienced with managing the long‐term complications of achondroplasia.
Transduction of surface and basal cells in Rhesus macaque lung following repeat dosing with AAV1CFTR.

To test the effectiveness of repeat dosing, we sprayed two doses (1013 vg each) of AAV1Δ27-264-CFTR into airways of four Rhesus monkeys at 0 and 30 days, followed by a single dose of 1013 vg of AAV1GFP on day 60. Monkeys were sacrificed on day 90. No adverse events occurred, indicating that AAV1 vectors are safe. An elevated anti-AAV1 neutralizing titer was established by the third dose. A positive ELISPOT to AAV capsid but not to CFTR occurred after the third dose in three monkeys. AAV1-CFTR and GFP vector were detectable in all lung sections and in heart, liver, and spleen. CFTR protein was higher in treated monkeys than in an untreated monkey. GFP protein was detected in treated lungs. Lung surface and keratin 5-positive basal cells showed higher CFTR staining than in the un-infected monkey and were positive for GFP staining, indicating widespread gene transduction by AAV1CFTR and GFP. Conclusion: AAV1 safely and effectively transduces monkey airway and basal cells. Both the significant numbers of vector genomes and transduction from AAV1CFTR and GFP virus seen in the monkeys 3 months after the first instillation suggest that repeat dosing with AAV1-based vectors is achievable.