Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple Breath Washout for Diagnosing Asthma and Persistent Wheeze in Young Children

Rationale: There is an unmet need for sensitive lung function tests for young children to aid in the diagnosis of asthma and wheezy disorders. We hypothesized that multiple breath washout (MBW) could be a valuable tool for such a purpose. Objectives: To compare the ability of MBW lung clearance index with traditional lung function measurements to discriminate between preschool children with well‐controlled asthma/persistent wheeze and healthy children. Methods: We investigated 646 children from the COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) mother‐child cohort, who completed MBW testing with nitrogen, spirometry, and plethysmography before age 6 years. Asthma/persistent wheeze was prospectively diagnosed according to a validated symptom‐based algorithm at the COPSAC clinic. Student's t tests and receiver operating characteristic curves were applied to analyze the discriminative ability of the lung function indices. Results: A total of 144 (22.3%) children were diagnosed with asthma/persistent wheeze during their first 6 years of life. Lung clearance index from MBW was not significantly different in children with versus those without asthma/persistent wheeze (mean standard deviation [SD] = 6.96 [1.14] vs. 6.95 [0.93], mean difference [95% confidence interval] = 0.02 [‐0.18 to 0.22], P = 0.86, area under the curve [AUC] = 0.48), whereas significant differences were observed for specific airway resistance from plethysmography (1.21 kPa/s [0.31] vs. 1.14 kPa/s [0.25]; +0.07 kPa/s [0.02‐0.13]; P < 0.01; AUC = 0.56) and spirometry forced expiratory volume in 1 second (FEV1) % predicted (99.4% [12.0] vs. 102.6% [12.5]; ‐3.2% [‐5.6 to ‐0.9]; P < 0.01; AUC = 0.56) and forced expiratory flow at 25‐75% (1.55 L/s [0.44] vs. 1.68 L/s [0.46]; ‐0.14 L/s [‐0.22 to ‐0.05]; P < 0.01; AUC = 0.58). FEV1 (L/s) and FEV1/forced vital capacity ratio were not significantly different (P > 0.4). Conclusions: MBW, spirometry, and plethysmography are not sensitive tools for diagnosing mild asthmatic disease in young children.
A Review of Automated Microinjection of Zebrafish Embryos

Cell microinjection is a technique of precise delivery of substances into cells and is widely used for studying cell transfection, signaling pathways, and organelle functions. Microinjection of the embryos of zebrafish, the third most important animal model, has become a very useful technique in bioscience. However, factors such as the small cell size, high cell deformation tendency, and transparent zebrafish embryo membrane make the microinjection process difficult. Furthermore, this process has strict, specific requirements, such as chorion softening, avoiding contacting the first polar body, and high-precision detection. Therefore, highly accurate control and detection platforms are critical for achieving the automated microinjection of zebrafish embryos. This article reviews the latest technologies and methods used in the automated microinjection of zebrafish embryos and provides a detailed description of the current developments and applications of robotic microinjection systems. The review covers key areas related to automated embryo injection, including cell searching and location, cell position and posture adjustment, microscopic visual servoing control, sensors, actuators, puncturing mechanisms, and microinjection.
Prognostic value of right ventricular dysfunction or elevated cardiac biomarkers in patients with low-risk pulmonary embolism: a systematic review and meta-analysis

Abstract Aims Patients with acute pulmonary embolism (PE) classified as low risk by the Pulmonary Embolism Severity Index (PESI), its simplified version (sPESI), or the Hestia criteria may be considered for early discharge. We investigated whether the presence of right ventricular (RV) dysfunction may aggravate the early prognosis of these patients. Methods and results We did a systematic review and meta-analysis of studies including low-risk patients with acute PE to investigate the prognostic value of RV dysfunction. Diagnosis of RV dysfunction was based on echocardiography or computed tomography pulmonary angiography. In addition, we investigated the prognostic value of elevated troponin or natriuretic peptide levels. The primary outcome was all-cause mortality at 30 days or during hospitalization. We included 22 studies (N = 3295 low-risk patients) in the systematic review: 21 were selected for quantitative analysis. Early all-cause mortality rates in patients with vs. without RV dysfunction on imaging were 1.8% [95% confidence interval (CI) 0.9–3.5%] vs. 0.2% (95% CI 0.03–1.7%), respectively, [odds ratio (OR) 4.19, 95% CI 1.39–12.58]. For troponins, rates were 3.8% (95% CI 2.1–6.8%) vs. 0.5% (95% CI 0.2–1.3%), (OR 6.25, 95% CI 1.95–20.05). For natriuretic peptides, only data on early PE-related mortality were available: rates were 1.7% (95% CI 0.4–6.9%) vs. 0.4% (95% CI 0.1–1.1%), (OR 3.71, 95% CI 0.81–17.02). Conclusions In low-risk patients with acute PE, the presence of RV dysfunction on admission was associated with early mortality. Our results may have implications for the management of patients who appear at low risk based on clinical criteria alone, but present with RV dysfunction as indicated by imaging findings or laboratory markers.
Mobile Microfluidics

Microfluidics platforms can program small amounts of fluids to execute a bio-protocol, and thus, can automate the work of a technician and also integrate a large part of laboratory equipment. Although most microfluidic systems have considerably reduced the size of a laboratory, they are still benchtop units, of a size comparable to a desktop computer. In this paper, we argue that achieving true mobility in microfluidics would revolutionize the domain by making laboratory services accessible during traveling or even in daily situations, such as sport and outdoor activities. We review the existing efforts to achieve mobility in microfluidics, and we discuss the conditions mobile biochips need to satisfy. In particular, we show how we adapted an existing biochip for mobile use, and we present the results when using it during a train ride. Based on these results and our systematic discussion, we identify the challenges that need to be overcome at technical, usability and social levels. In analogy to the history of computing, we make some predictions on the future of mobile biochips. In our vision, mobile biochips will disrupt how people interact with a wide range of healthcare processes, including medical testing and synthesis of on-demand medicine.
Updated S3-Guideline Ulcerative Colitis. German Society for Digestive and Metabolic Diseases (DGVS)

Abstract This guideline provides evidence-based key recommendations for diagnosis and treatment of ulcerative colitis and upgrades the 2011 version. The guideline was developed by an interdisciplinary team of gastroenterologists, surgeons, pathologists, nutrition experts, and patient support groups under the auspice of the German Society for Gastroenterology and Metabolic Diseases. The guideline used structural S3 consensus-based methodology and includes statements on clinical practice, prevention, infectiological problems, surgery and nutrition.
Association of metformin use with ovarian cancer incidence and prognosis: a systematic review and meta-analysis

Background Some clinical and basic research studies have indicated that exposure to metformin might have protective effects against ovarian cancer. However, results from epidemiologic studies have been inconsistent. We performed a meta-analysis to evaluate the effect of metformin use on the risk of ovarian cancer occurrence and mortality. Methods Multiple databases were searched to identify studies on the association between use of metformin and risk of ovarian cancer or prognosis, up to August 2018. Relevant information for analysis was extracted. A random-effects model was used to calculate the pooled risk estimate. Results Thirteen articles were included, of which six articles focused on ovarian cancer incidence and the others focused on prognosis. The pooled OR for ovarian cancer occurrence and mortality comparing metformin use with non-use or use of other hypoglycemic drugs was 0.76 (95% CI 0.62 to 0.93, p = 0.008) and 0.55 (95% CI 0.36 to 0.84, p = 0.006), respectively. Moderate to substantial heterogeneity was observed across included studies. Conclusions Our findings demonstrate that use of metformin was significantly associated with a lower incidence and a better prognosis of ovarian cancer in patients with diabetes. Well-designed interventional studies are warranted to confirm our findings.
Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder

With the recent 50th anniversary of the first publication on Rett syndrome, and the almost 20 years since the first report on the link between Rett syndrome and MECP2 mutations, it is important to reflect on the tremendous advances in our understanding and their implications for the diagnosis and treatment of this neurodevelopmental disorder. Rett syndrome features an interesting challenge for biologists and clinicians, as the disorder lies at the intersection of molecular mechanisms of epigenetic regulation and neurophysiological alterations in synapses and circuits that together contribute to severe pathophysiological endophenotypes. Genetic, clinical, and neurobiological evidences support the notion that Rett syndrome is primarily a synaptic disorder, and a disease model for both intellectual disability and autism spectrum disorder. This review examines major developments in both recent neurobiological and preclinical findings of Rett syndrome, and to what extent they are beginning to impact our understanding and management of the disorder. It also discusses potential applications of knowledge on synaptic plasticity abnormalities in Rett syndrome to its diagnosis and treatment.
Documentation of asthma control and severity in pediatrics: analysis of national office-based visits

Abstract Objective: To evaluate the extent of documentation of asthma control and severity and associated characteristics among pediatric asthma patients in office-based settings. Methods: This cross-sectional study utilized data from the 2012–2015 National Ambulatory Medical Care Survey (NAMCS). Patients aged 6–17 years with a diagnosis of asthma were included. Weighted descriptive analysis examined the extent of documentation and uncontrolled asthma; while logistic regression evaluated associated characteristics. Results: Overall, there were 2.47 million (95% confidence interval, 95% CI: 2.04–2.90) average annual visits with asthma as a primary diagnosis. Asthma control and severity was documented in only 36.1% and 33.8% of the visits, respectively. An established patient (odds ratio, OR = 3.81), Hispanic ethnicity (OR = 2.10), chronic sinusitis (OR = 5.59), and visits in the Northeast (OR = 2.12) and Midwest (OR = 2.25) regions had higher odds of documented asthma control status, whereas undocumented asthma severity (OR = 0.02), and visits in spring (OR = 0.34), had lower odds. Osteopathic doctors (OR = 0.18), visits in the Northeast region (OR = 0.23), chronic sinusitis (OR = 0.08), and undocumented asthma control status (OR = 0.03) had lower odds of documented asthma severity, whereas visits in spring (OR = 3.88) and autumn (OR = 3.32) had higher odds. Moderate/severe persistent asthma (OR = 15.35) had higher odds of uncontrolled asthma (as compared to intermittent asthma), while visits in the summer (OR = 0.14) had lower odds. Conclusion: The findings of this study suggest a critical need to increase the documentation of asthma severity and control to improve quality of asthma care in children.
Impact of External Quality Assurance on the Quality of Xpert MTB/RIF Testing in Viet Nam

Following the endorsement of the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) by the World Health Organization (WHO) in 2010, Viet Nam’s National Tuberculosis Control Program (NTP) began using GeneXpert instruments in NTP laboratories. In 2013, Viet Nam’s NTP implemented an Xpert MTB/RIF external quality assurance (EQA) program in collaboration with the U.S. ABSTRACT Following the endorsement of the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) by the World Health Organization (WHO) in 2010, Viet Nam’s National Tuberculosis Control Program (NTP) began using GeneXpert instruments in NTP laboratories. In 2013, Viet Nam’s NTP implemented an Xpert MTB/RIF external quality assurance (EQA) program in collaboration with the U.S. Centers for Disease Control and Prevention (CDC) and the Foundation for Innovative New Diagnostics (FIND). Proficiency-testing (PT) panels comprising five dried tube specimens (DTS) were sent to participating sites approximately twice a year from October 2013 to July 2016. The number of enrolled laboratories increased from 22 to 39 during the study period. Testing accuracy was assessed by comparing reported and expected results; percentage scores were assigned; and feedback reports were provided to sites. On-site evaluation (OSE) was conducted for underperforming laboratories. The results from the first five rounds demonstrate the positive impact of PT and targeted OSE visits on testing quality. On average, for every additional round of feedback, the odds of achieving PT scores of ≥80% increased 2.04-fold (95% confidence interval, 1.39- to 3.00-fold). Future work will include scaling up PT to all sites and maintaining the performance of participating laboratories while developing local panel production capacity.
The sympathetic role of glutamatergic paraventricular nucleus neurons in blood pressure regulation

Hypertension is among the most powerful modifiable risk factors for cardiovascular and cerebrovascular diseases. Although the underlying mechanism is complex and still under investigation, it is well-accepted that the sympathetic nervous system probably plays a central role. A vast network of neurons, including the hypothalamic paraventricular nucleus (PVN) and regions of the brainstem are crucially involved in autonomic control of blood pressure (BP). PVN circuitry provides tonic input to the rostral ventrolateral medulla (RVLM) controlling sympathetic outflow through an array of glutamatergic and gamma-aminobutyric acid (GABA)-ergic neurons. However, it is still unknown how PVN glutamatergic neurons contribute to BP regulation. In a recent issue of The Journal of Physiology, Basting and colleagues (2018) hypothesized that overexcitation of the PVN-RVLM glutamatergic interneuronal population leads to excess sympathetic outflow, evoking an increase in baseline BP and contributing to hypertension. To address the unknown role of PVN-RVLM excitatory glutamatergic interneurons in the development of hypertension through overactivation of the sympathetic nervous system, Basting et al. (2018) completed a set of experiments in mouse models that involved unilateral and bilateral manipulation of PVN-RVLM excitatory glutamatergic interneurons, and assessed their role in both RVLM activity and BP. First, the researchers conducted an in vivo optogenetic procedure in conscious mice to investigate the effects of PVN-RVLM glutamatergic interneuronal activation on BP using channelrhodopsin-2 (ChR2) under the calcium/calmodulin-dependent protein kinase type Iiα (CaMKIIα) promoter (AAV-CamKIIα-ChR2-eYFP sero-type 2) in a selective manner such that they would activate these neurons unilaterally. This approach demonstrated causally the role of PVN-RVLM excitatory glutamatergic interneurons in increasing BP to hypertensive levels. Second, PVN-RVLM excitatory glutamatergic interneuronal lesioning using AAV-flex-taCasp3-TEVp in a bilateral manner in vesicular glutamate2 Cre-recombinase (vGlut2-Cre) mice was used to test the effects of complete disruption of excitatory signalling between the PVN and RVLM on downstream sympathetic outflow and BP. For further investigation, the researchers used the deoxycorticosterone acetate (DOCA)-salt model to investigate the role of PVN-RVLM excitatory glutamatergic interneurons in the development of hypertension through gainand loss-of-function procedures. This study supported their hypothesis by demonstrating that disrupting a portion of the PVN-RVLM excitatory glutamatergic interneurons neuronal population led to a loss of both BP regulation and sympathetic outflow, contributing to the manifestation of hypertension.
Muscle wasting and branched‐chain amino acid, alpha‐ketoglutarate, and ATP depletion in a rat model of liver cirrhosis

The aim of the study was to examine whether a rat model of liver cirrhosis induced by carbon tetrachloride (CCl4) is a suitable model of muscle wasting and alterations in amino acid metabolism in cirrhotic humans. Rats were treated by intragastric gavage of CCl4 or vehicle for 45 days. Blood plasma and different muscle types—tibialis anterior (mostly white fibres), soleus (red muscle) and extensor digitorum longus (white muscle) ‐ were analysed at the end of the study. Characteristic biomarkers of impaired hepatic function were found in the plasma of cirrhotic animals. The weights and protein contents of all muscles of CCl4‐treated animals were lower when compared with controls. Increased concentrations of glutamine (GLN) and aromatic amino acids (phenylalanine and tyrosine) and decreased concentrations of branched‐chain amino acids (BCAA), glutamate (GLU), alanine and aspartate were found in plasma and muscles. In the soleus muscle, GLN increased more and GLU and BCAA decreased less than in the extensor digitorum and tibialis muscles. Increased chymotrypsin‐like activity (indicating enhanced proteolysis) and decreased α‐ketoglutarate and ATP levels were found in muscles of cirrhotic animals. ATP concentration also decreased in blood plasma. It is concluded that a rat model of CCl4‐induced cirrhosis is a valid model for the investigation of hepatic cachexia that exhibits alterations in line with a theory of role of ammonia in pathogenesis of BCAA depletion, citric cycle and mitochondria dysfunction, and muscle wasting in cirrhotic subjects. The findings indicate more effective ammonia detoxification to GLN in red than in white muscles.
Aquaporins in Renal Diseases

Aquaporins (AQPs) are a family of highly selective transmembrane channels that mainly transport water across the cell and some facilitate low-molecular-weight solutes. Eight AQPs, including AQP1, AQP2, AQP3, AQP4, AQP5, AQP6, AQP7, and AQP11, are expressed in different segments and various cells in the kidney to maintain normal urine concentration function. AQP2 is critical in regulating urine concentrating ability. The expression and function of AQP2 are regulated by a series of transcriptional factors and post-transcriptional phosphorylation, ubiquitination, and glycosylation. Mutation or functional deficiency of AQP2 leads to severe nephrogenic diabetes insipidus. Studies with animal models show AQPs are related to acute kidney injury and various chronic kidney diseases, such as diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma. Experimental data suggest ideal prospects for AQPs as biomarkers and therapeutic targets in clinic. This review article mainly focuses on recent advances in studying AQPs in renal diseases.
Acupuncture or metformin to improve insulin resistance in women with polycystic ovary syndrome: study protocol of a combined multinational cross sectional case-control study and a randomised controlled trial

Introduction Polycystic ovary syndrome (PCOS) is linked to hyperinsulinemia and insulin resistance with dysfunctional glucose metabolism. Pilot studies suggests that acupuncture treatment with combined manual and low-frequency electrical stimulation (electroacupuncture (EA)) of the needles decrease circulating glycated haemoglobulin (HbA1c) and homeostatic model assessment-insulin resistance. Therefore, we here aim to investigate if acupuncture treatment or metformin together with lifestyle or lifestyle management alone improves insulin sensitivity and related symptoms in overweight/obese women with PCOS. Methods and analysis This is a two-centre multinational (Sweden and China), cross-sectional case–control study combined with an open-labelled randomised controlled trial (RCT). Participants are randomised to one of three groups: (1) EA 2–3 times/week during 4 months+lifestyle management; (2) metformin, 500 mg, three/day during 4 months+lifestyle management; or (3) lifestyle management alone. The primary outcome measure in the RCT is changes in HbA1C. A total of 123 obese overweight women with PCOS will be enrolled and randomised into one of the three groups with a target power of at least 80% and 5% significance level based on two-sided tests. Ethics and dissemination The study has been approved by the Regional Ethical Review Board of Stockholm and of Peking University Third Hospital, China. Primary outcome data of the RCT will be published in a relevant journal together with supporting secondary outcome measurements. Further, outcome measurements will be published in separate papers as well as case–control data. Expected results We anticipate that EA and metformin, both with lifestyle management, are equally effective and superior to lifestyle management alone for improvement of glycaemic control. Trial registration numbers NCT02647827 and EudraCT2015-004250-18.
Afraid of one afraid of all: When threat associations spread across face-types

Abstract Fear can be acquired for objects not inherently associated with threat (e.g. birds), and this threat may generalize from prototypical to peripheral category members (e.g. crows vs. penguins). When categorizing people, pervasive stereotypes link Black men to assumed violence and criminality. Faces with Afrocentric features (prototypical) are more often associated with threat and criminality than non-Afrocentric (peripheral) faces regardless of whether the individual is Black or White. In this study, using a priming paradigm, threat associations related to negative racial stereotypes were tested as a vehicle for spreading fear across face-type categories. Results showed more negative than positive judgments for White face targets but only when the prime was primarily non-Afrocentric (i.e. Eurocentric). Black face targets were judged more negatively than positively regardless of prime. This suggests some cognitive processes related to threat generalizations of objects extend to complex social categories.