Miracle-dz/UniFAR-FTUs huggingface dataset:
Die Sensitivität und Spezifität des Mini-Audio-Tests (MAT) für unterschiedliche Hörverlustschwellen

ZusaMmenfassung Hintergrund Eine nichtbehandelte Schwerhörigkeit hat einen erheblichen Einfluss auf die Morbidität. Zur Früherkennung wurde der Mini-Audio-Test (MAT) entwickelt. Im Rahmen einer Nachuntersuchung soll untersucht werden, welche Werte sich für die Sensitivität, Spezifität und prädiktiven Werte für einen minimal zu detektierenden Hörverlust von 25, 30, 35 und 40 dB sowohl in mindestens 1 der 4 Oktavfrequenzen zwischen 0,5 und 4 kHz als auch in den über diesen Frequenzen gemittelten Hörverlust ergeben. Methode Nachuntersucht wurden Daten, die 2016 und 2017 erhoben wurden. Bestimmt wurden die Sensitivität, Spezifität und die negativ und positiv prädiktiven Werte mittels einer logistischen Regression. Ergebnisse Die Sensitivität des MAT stieg in beiden Altersgruppen mit zunehmendem zu detektierendem Hörverlust an, die Spezifität sank analog. Die positiv prädiktiven Werte waren für die Älteren höher als für die Jüngeren und sanken mit steigendem, minimal zu detektierendem Hörverlust. Dabei lagen die Werte für die gemittelten Frequenzen deutlich unter denen, die den Hörverlust nur in 1 Frequenz berücksichtigen. Die negativ prädiktiven Werte verhielten sich genau entgegengesetzt. Schlussfolgerung Die Werte sind für Ältere ab dem 60. Lebensjahr deutlich schlechter als für Jüngere ab dem 50. Lebensjahr. Dies lässt es umso wichtiger erscheinen, dass bereits ein erstes Hörscreening ab dem 50. Lebensjahr durchgeführt wird, um einen individuellen Hörverlust realistisch einschätzen zu können. Nur durch eine rechtzeitige Hörrehabilitation können negative Folgen einer unbehandelten Schwerhörigkeit positiv beeinflusst werden.
Codon usage bias affects α-amylase mRNA level by altering RNA stability and cytosine methylation patterns in Escherichia coli.

Codon usage bias exists in almost every organism, and has been reported to regulate protein translation efficiency and folding. Besides the translational level, the preliminary role of codon usage bias on gene transcription has also been revealed in some eukaryotes such as Neurospora crassa. Here we took the α-amylase coding gene (amyA) as an example, and examined the role of codon usage bias in regulating gene expression in the typical prokaryote Escherichia coli. We confirmed the higher translation efficiency on codon optimized amyA RNAs, and found that RNA level itself was also affected by codon optimization. The decreased RNA level was at least partially contributed by altered mRNA stability at the post-transcriptional level. Codon optimization also altered the number of cytosine methylation sites. Examinations on dcm knockouts suggested that cytosine methylation may be a minor mechanism adopted by codon bias to regulate gene RNA levels. More studies are required to verify its global effect and the detailed mechanism on transcription.
Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives

Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of hepatocellular carcinoma (HCC). Despite different mechanism of primary liver injury and disease-specific cell responses, the progression of fibrotic liver disease follows shared patterns across the main liver disease etiologies. Scientific discoveries within the last decade have transformed the understanding of the mechanisms of liver fibrosis. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. However, reversal often occurs too slowly or too infrequent to avoid life-threatening complications particularly in advanced fibrosis. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, their anti-fibrotic effects in clinical trials have been limited or absent. Thus, no approved therapy exists for liver fibrosis. In this review we summarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.
Sodium Imbalance in Mice Results Primarily in Compensatory Gene Regulatory Responses in Kidney and Colon, but Not in Taste Tissue

Renal excretion and sodium appetite provide the basis for sodium homeostasis. In both the kidney and tongue, the epithelial sodium channel (ENaC) is involved in sodium uptake and sensing. The diuretic drug amiloride is known to block ENaC, producing a mild natriuresis. However, amiloride is further reported to induce salt appetite in rodents after prolonged exposure as well as bitter taste impressions in humans. To examine how dietary sodium content and amiloride impact on sodium appetite, mice were subjected to dietary salt and amiloride intervention and subsequently analyzed for ENaC expression and taste reactivity. We observed substantial changes of ENaC expression in the colon and kidney confirming the role of these tissues for sodium homeostasis, whereas effects on lingual ENaC expression and taste preferences were negligible. In comparison, prolonged exposure to amiloride-containing drinking water affected β- and αENaC expression in fungiform and posterior taste papillae, respectively, next to changes in salt taste. However, amiloride did not only change salt taste sensation but also perception of sucrose, glutamate, and citric acid, which might be explained by the fact that amiloride itself activates bitter taste receptors in mice. Accordingly, exposure to amiloride generally affects taste impression and should be evaluated with care.
Diffuse Lacy Reticular Calcinosis in Juvenile Dermatomyositis.

A 14-year-old girl presented with multiple tender skin-colored to hyperpigmented firm-to-hard nodules over lower abdomen, buttocks, and thighs (Fig. 1A), along with proximal muscle weakness affecting both upper and lower limbs. There was history of periorbital erythema and edema, suggestive of a heliotrope rash. Her laboratory parameters were significant for positive antinuclear antibody (1:100, 1+ speckled pattern) and elevated lactate dehydrogenase level (708 U/L; reference range, 200–420 U/L) and erythrocyte sedimentation rate (45 mm/h). Complete blood cell count, liver and renal function tests, serum calcium, and creatine phosphokinase were within normal limits. Electromyography showed an inflammatory myopathic pattern. Histopathology from the nodule on left thigh showed irregular basophilic calcium deposits in the deep dermis and subcutis, along with foci of hyalinization in the lobular panniculus (Fig. 1B). Radiographic imaging demonstrated subcutaneous calcification in a lacy reticular pattern encasing the lower trunk, thighs, and legs (Fig. 2). The patient was initiated on monthly pulsed corticosteroids (dexamethasone 50mg daily for 3 days), weeklymethotrexate 10mg, hydroxychloroquine sulphate 100 mg/d, and intravenous pamidronate (1 mg/kg per day for 3 days every month), along with supportive physiotherapy. There was good improvement in muscle strength in the next 3 months, but only minimal improvement in calcinosis cutis. Juvenile dermatomyositis is characterized by a combination of cutaneous lesions such as heliotrope rash, Gottron's papules and confluent violaceous macular erythema, and symmetrical proximal myopathy. Unlike its adult counterpart, juvenile dermatomyositis has a higher incidence of calcinosis, vasculopathy, and metabolic abnormalities such as insulin resistance. Calcinosis cutis occurs due to dystrophic deposition of insoluble calcium salts in the skin, subcutaneous tissues, fascia, and muscle, and has been reported to occur in 10% to 70% of patients with juvenile dermatomyositis. It is usually related to longstanding and severe disease, delayed initiation of treatment, or inadequately treated disease, and is potentially linked to genetic polymorphisms in TNF-α-308 allele. Radiologically, 4 patterns of calcinosis in juvenile dermatomyositis have been described:
Downgrading from Biopsy Grade Group 4 Prostate Cancer in Patients Undergoing Radical Prostatectomy for High or Very High Risk Prostate Cancer.

OBJECTIVES To examine rates of Grade Group (GG) 4 downgrading at radical prostatectomy (RP) among men diagnosed with high (HR)- and very-high risk (VHR) prostate cancer (PCa) at biopsy. METHODS A pooled cohort of 1776 patients from three tertiary referral centers who underwent RP for either National Comprehensive Cancer Network (NCCN) HR (PSA >20 ng/ml, or GG 4-5, or clinical stage ≥T3) or VHR (primary Gleason pattern 5, or more than 4 biopsy cores with GG 4-5, or ≥2 HR features) disease from 2005-2015 were reviewed. 893 patients with GG 4 disease at biopsy were identified and 726 patients were available for analysis. Multivariable logistic regression models were fit to determine factors associated with downgrading to GG ≤ 3 at RP. RESULTS Obtained: Overall, 333 (45%) patients were downgraded to GG ≤3 at RP. 198 (27%) patients had concordant GG 4 biopsy and RP pathology and 195 (27%) were upgraded at RP to GG 5. 49% of HR patients with biopsy GG 4 had any downgrading versus 29% of VHR patients (p<.0001). Downgrading to GG ≤ 2 occurred in 16% (98/604) of HR and 7% (8/122) of VHR patients (p<0.01). Downgraded patients had a lower PSA, fewer positive biopsy cores, and lower clinical stage (p<0.01). On multivariable analysis, fewer positive biopsy cores were significantly associated with downgrading at RP (p<0.01. CONCLUSION In this cohort of patients with HR/VHR PCa, downgrading from biopsy GG 4 at RP occurred less frequently than in other published reports. Any downgrading was significantly less common in VHR compared to HR patients, and downgrading to GG ≤2 occurred in a minority of cases in both HR and VHR patients.
Potential Health Effects of Tea

Brewed tea (from the Camellia sinensis plant) is the second most commonly consumed beverage in the world, and its consumption has been associated with several human health benefits. Tea polyphenols are absorbed in the intestine following consumption and metabolized by both human and microbial systems to yield a mixture of complex metabolites that can be found in circulation and throughout the body. Identification of tea phenolic constituents and their metabolites has served to strengthen the association between tea consumption and specific health benefits, as well as to measure potential differences between tea product forms. The current state of research suggests that long-term consumption of tea and tea polyphenols may provide distinct health benefits, with the strongest associations being the promotion of cardiovascular health, as well as antidiabetic and antiobesity effects. However, much regarding tea and health remains to be discovered. This includes development of a better understanding of the role of abundant oxidized polyphenol forms in oolong and black tea, whose bioavailability and specific role in health benefits remain unknown. This technical summary focuses on tea polyphenol bioaccessibility/bioavailability, discusses potential bioactivity, and highlights studies that link tea consumption and health. Nutr Today. 2018;53(5):213Y228
Brief Exposure to Infants Activates Social and Intergroup Vigilance

Among humans, simply looking at infants can activate affiliative and nurturant behaviors. However, it remains unknown whether mere exposure to infants also activates other aspects of the caregiving motivational system, such as generalized defensiveness in the absence of immediate threats. Here, we demonstrate that simply viewing faces of infants (especially from the ingroup) may heighten vigilance against social threats and support for institutions that purportedly maintain security. Across two studies, participants viewed and rated one among several image types (between-subjects design): Infants, adult males, adult females, and puppies in Study 1, and infants of varying racial/ethnic groups (including one’s ingroup) and puppies in Study 2. Following exposure to one of these image types, participants completed measures of intergroup bias from a range of outgroups that differed in perceived threat, belief in a dangerous world, right-wing authoritarianism and social-political conservatism (relative to liberalism). In Study 1 (United States), stronger affiliative reactions to images of infants (but not adults or puppies) predicted stronger perceptions of a dangerous world, endorsement of right-wing authoritarianism, and support for social-political conservatism (relative to liberalism). Study 2 (Italy) revealed that exposure to images of ingroup infants (compared to outgroup infants) increased intergroup bias against outgroups that are characterized as threatening (immigrants and Arabs) and increased conservatism. These findings suggest a predisposed preparedness for social vigilance in the mere suggested presence of infants (e.g., viewing images) even in the absence of salient external threats.
Integrating GWAS with bulk and single-cell RNA-sequencing reveals a role for LY86 in the anti-Candida host response

Candida bloodstream infection, i.e. candidemia, is the most frequently encountered life-threatening fungal infection worldwide, with mortality rates up to almost 50%. In the majority of candidemia cases, Candida albicans is responsible. Worryingly, a global increase in the number of patients who are susceptible to infection (e.g. immunocompromised patients), has led to a rise in the incidence of candidemia in the last few decades. Therefore, a better understanding of the anti-Candida host response is essential to overcome this poor prognosis and to lower disease incidence. Here, we integrated genome-wide association studies with bulk and single-cell transcriptomic analyses of immune cells stimulated with Candida albicans to further our understanding of the anti-Candida host response. We show that differential expression analysis upon Candida stimulation in single-cell expression data can reveal the important cell types involved in the host response against Candida. This confirmed the known major role of monocytes, but more interestingly, also uncovered an important role for NK cells. Moreover, combining the power of bulk RNA-seq with the high resolution of single-cell RNA-seq data led to the identification of 27 Candida-response QTLs and revealed the cell types potentially involved herein. Integration of these response QTLs with a GWAS on candidemia susceptibility uncovered a potential new role for LY86 in candidemia susceptibility. Finally, experimental follow-up confirmed that LY86 knockdown results in reduced monocyte migration towards the chemokine MCP-1, thereby implying that this reduced migration may underlie the increased susceptibility to candidemia. Altogether, our integrative systems genetics approach identifies previously unknown mechanisms underlying the immune response to Candida infection.
Potential Molecular Pathways Related to Pulmonary Artery Aneurysm Development: Lessons to Learn from the Aorta

Pulmonary arterial hypertension (PAH) is a rare disease caused by pulmonary vascular remodeling. Current vasodilator treatments have substantially improved patients’ survival. This improved survival has led to the appearance of complications related to conditions previously underdiagnosed or even ignored, such as pulmonary artery aneurysm (PAA). The presence of a dilated pulmonary artery has been shown to be related to an increased risk of sudden cardiac death among PAH patients. This increased risk could be associated to the development of left main coronary artery compression or pulmonary artery dissection. Nevertheless, very little is currently known about the molecular mechanisms related to PAA. Thoracic aortic aneurysm (TAA) is a well-known condition with an increased risk of sudden death caused by acute aortic dissection. TAA may be secondary to chronic exposure to classic cardiovascular risk factors. In addition, a number of genetic variants have been shown to be related to a marked risk of TAA and dissection as part of multisystemic syndromes or isolated familial TAA. The molecular pathways implied in the development of TAA have been widely studied and described. Many of these molecular pathways are involved in the pathogenesis of PAH and could be involved in PAA. This review aims to describe all these common pathways to open new research lines that could help lead to a better understanding of the pathophysiology of PAH and PAA and their clinical implications.
Evaluation of factors affecting morbidity and mortality in pneumonectomy patients

Abstract Background The aim of this study was to evaluate risk factors associated with morbidity and mortality after pneumonectomy in non-small cell lung cancer patients. Methods The study included 107 patients who underwent pneumonectomy for non-small cell lung cancer between January 2013 and December 2018. Prognostic factors affecting mortality and morbidity were investigated. Results The patient group included 10 women (9.3%) and 97 men (90.7%) with a mean age of 59.5 ± 8.5 years. Seventy-three patients (68.2%) underwent standard pneumonectomy and 34 (31.8%) underwent extended pneumonectomy. Nine patients (8.4%) received induction chemotherapy. Complications occurred in 33 patients (30.8%). Complications were classified as surgical, cardiovascular, pulmonary, or infectious. Charlson Comorbidity Index (CCI) > 3 and right-side resection were significant risk factors for the development of complications. The most common complication was atrial fibrillation. Eleven patients developed a bronchopleural fistula. The 30-day postoperative mortality rate was 6.5% (n = 7). Mortality was not associated with any demographic and surgical characteristics other than CCI > 3 (p = .05). Conclusion The results of this study indicate that our pneumonectomy outcomes are acceptable despite high morbidity and mortality rates. Appropriate patient selection for pneumonectomy is as important as complication management. High-comorbidity patients should undergo these procedures in experienced centers.
Incidence and prevalence of intravenous medication errors in the UK: a systematic review

Objectives Medication error is the most common type of medical error, and intravenous medicines are at a higher risk as they are complex to prepare and administer. The WHO advocates a 50% reduction of harmful medication errors by 2022, but there is a lack of data in the UK that accurately estimates the true rate of intravenous medication errors. This study aimed to estimate the number of intravenous medication errors per 1000 administrations in the UK National Health Service and their associated economic costs. The rate of errors in prescribing, preparation and administration, and rate of different types of errors were also extracted. Methods MEDLINE, Embase, Cochrane central register of clinical trials, Database of Abstracts of Reviews of Effectiveness, National Health Service Economic Evaluation Database and the Health Technology Appraisals Database were searched from inception to July 2017. Epidemiological studies to determine the incidence of intravenous medication errors set wholly or in part in the UK were included. 228 studies were identified, and after screening, eight papers were included, presenting 2576 infusions. Data were reviewed and extracted by a team of five reviewers with discrepancies in data extraction agreed by consensus. Results Five of eight studies used a comparable denominator, and these data were pooled to determine a weighted mean incidence of 101 intravenous medication errors per 1000 administrations (95% CI 84 to 121). Three studies presented prevalence data but these were based on spontaneous reports only; therefore it did not support a true estimate. 32.1% (95% CI 30.6% to 33.7%) of intravenous medication errors were administration errors and ‘wrong rate’ errors accounted for 57.9% (95% CI 54.7% to 61.1%) of these. Conclusion Intravenous medication errors in the UK are common, with half these of errors related to medication administration. National strategies are aimed at mitigating errors in prescribing and preparation. It is now time to focus on reducing administration error, particularly wrong rate errors.
Posterior Corneal Surface Changes After Pterygium Excision Surgery.

PURPOSE To evaluate the effect of pterygium excision on the posterior corneal surface and analyze the factors associated with those changes. METHODS A prospective, interventional study including 33 eyes of 31 patients who underwent pterygium excision at the Tel Aviv Medical Center (Tel Aviv, Israel). Exclusion criteria included corneal dystrophy, pseudopterygium, corneal scarring, or previous ocular surgery in the treated eye. Data were obtained by using the Galilei dual Scheimpflug analyzer. Recorded posterior corneal data included steep keratometry, flat keratometry, mean keratometry, corneal astigmatism, best-fit sphere, and the squared eccentricity index (e). Posterior surgically induced astigmatism (SIA) was calculated to demonstrate the astigmatic effect of surgery. Anterior-segment high resolution optical coherence tomography was used to measure pterygium dimensions (depth and horizontal/vertical size). RESULTS The mean age was 53.7 ± 16.7 years. Posterior corneal SIA was 0.9 ± 1.1 D (P < 0.001) and was significantly correlated with age (r = 0.568, P = 0.002), horizontal pterygium size (r = 0.387, P = 0.046), and preoperative posterior astigmatism (r = 0.688, P < 0.001). In a multivariable analysis, only age (coefficient = 0.010, P = 0.038) and preoperative posterior astigmatism (coefficient = 0.648, P = 0.002) remained significant. Pterygium dimensions were not significantly associated with SIA magnitude. Flat keratometry steepened by 0.5 ± 1.1 D (P = 0.019), mean keratometry steepened by 0.3 ±0.6 D (P = 0.035), posterior astigmatism was reduced by 0.4 ± 1.2 D (P = 0.072), and e decreased by 5.1 ± 17.3 (P = 0.021). CONCLUSIONS Pterygium excision has a significant astigmatic effect on the posterior corneal surface. The astigmatic effect increases with age and with higher preoperative posterior astigmatism. Pterygium depth and size are not associated with the degree of surgical astigmatic effect.
Patient personality and psychotherapist reactions in individual psychotherapy setting: a systematic review.

Despite the importance of psychotherapists' subjective experience working with patients with mental issues, little is known about the relationship between therapists' emotional reactions and patients' personality problems. The present study is a systematic review of quantitative research on the association between patients' personality pathology and psychotherapists' emotional, cognitive and behavioural reactions in individual psychotherapy setting. A systematic database search (from January 1980 to August 2019) supplemented by manual searches of references and citations identified seven relevant studies. Significant and consistent relationships were found between therapist reactions and specific personality traits or disorders. In general, odd and eccentric patients tend to evoke feelings of distance and disconnection; emotionally dysregulated patients tend to evoke anxiety and incompetence, and anxious and withdrawn patients tend to evoke sympathy and concern. However, the relatively small sample of studies and methodological inconsistencies across studies limit firm conclusions and suggest the need for more systematic research. Findings from this review indicate that patients who share the same personality disorder or symptoms tend to evoke specific and similar cognitive, emotional and behavioural reactions in their therapists. This suggests that therapists overall reactions toward patients may be source of valuable diagnostic information.