Miracle-dz/UniFAR-FTUs huggingface dataset:
Ratiometric pH imaging using a 1,2-dioxetane chemiluminescence resonance energy transfer sensor in live animals.

Regulation of physiological pH is integral for proper whole-body and cellular function, and disruptions in pH homeostasis can be both a cause and effect of disease. In light of this, many methods have been developed to monitor pH in cells and animals. In this study, we report a chemiluminescence resonance energy transfer (CRET) probe Ratio-pHCL-1, comprised of an acrylamide 1,2-dioxetane chemiluminescent scaffold with an appended pH-sensitive carbofluorescein fluorophore. The probe provides an accurate measurement of pH between 6.8-8.4, making it a viable tool for measuring pH in biological systems. Further, its ratiometric output is independent of confounding variables. Quantification of pH can be accomplished both using common luminescence spectroscopy and advanced optical imaging methods. Using an IVIS Spectrum, pH can be measured through tissue with Ratio-pHCL-1, which is shown in vitro and calibrated in sacrificed mouse models. Intraperitoneal injections of Ratio-pHCL-1 into live mice show high photon outputs and consistent increases in flux ratio when measured at pH 6, 7, and 8.
Clinician and patient beliefs about diagnostic imaging for low back pain: a systematic qualitative evidence synthesis

Objective Overuse of diagnostic imaging for patients with low back pain remains common. The underlying beliefs about diagnostic imaging that could drive overuse remain unclear. We synthesised qualitative research that has explored clinician, patient or general public beliefs about diagnostic imaging for low back pain. Design A qualitative evidence synthesis using a thematic analysis. Methods We searched MEDLINE, EMBASE, CINAHL, AMED and PsycINFO from inception to 17 June 2019. Qualitative studies that interviewed clinicians, patients and/or general public exploring beliefs about diagnostic imaging for low back pain were included. Four review authors independently extracted data and organised these according to themes and subthemes. We used the Critical Appraisal Skills Programme tool to critically appraise included studies. To assess confidence in review findings, we used the GRADE-Confidence in the Evidence from Reviews of Qualitative Research method. Results We included 69 qualitative studies with 1747 participants. Key findings included: Patients and clinicians believe diagnostic imaging is an important test to locate the source of low back pain (33 studies, high confidence); patients with chronic low back pain believe pathological findings on diagnostic imaging provide evidence that pain is real (12 studies, moderate confidence); and clinicians ordered diagnostic imaging to reduce the risk of a missed diagnosis that could lead to litigation, and to manage patients’ expectations (12 studies, moderate confidence). Conclusion Clinicians and patients can believe that diagnostic imaging is an important tool for locating the source of non-specific low back pain. Patients may underestimate the harms of unnecessary imaging tests. These beliefs could be important targets for intervention. PROSPERO registration number CRD42017076047.
Developmental Biology of Forensically Important Beetle, Necrophila (Calosilpha) brunnicollis (Coleoptera: Silphidae)

Abstract The postmortem interval (PMI) estimation, in cases where the body was discovered in an advanced stage of decomposition, is predominantly based on entomological evidence. However, very few forensically important species are sufficiently known in detail to allow a practical application. One of them is the carrion beetle, Necrophila (Calosilpha) brunnicollis (Kraatz, 1877). Its development from egg to adulthood was studied under a range of ecologically relevant constant temperatures to find parameters of thermal summation models. Developmental sexual dimorphism and the presence of developmental rate isomorphy were investigated. Herein we present the lower developmental thresholds and sum of effective temperatures for all developmental stages of N. brunnicollis (egg, first–third larval instar, postfeeding stage, and pupae). We did not find any evidence of developmental sexual dimorphism nor was the presence of developmental rate isomorphy confirmed. Our results present the first thermal summation model of the East Asian carrion beetle that can be used for the PMI estimation.
Shared and modality-specific brain regions that mediate auditory and visual word comprehension

Visual speech carried by lip movements is an integral part of communication. Yet, it remains unclear in how far visual and acoustic speech comprehension are mediated by the same brain regions. Using multivariate classification of full-brain MEG data, we first probed where the brain represents acoustically and visually conveyed word identities. We then tested where these sensory-driven representations are predictive of participants’ trial-wise comprehension. The comprehension-relevant representations of auditory and visual speech converged only in anterior angular and inferior frontal regions and were spatially dissociated from those representations that best reflected the sensory-driven word identity. These results provide a neural explanation for the behavioural dissociation of acoustic and visual speech comprehension and suggest that cerebral representations encoding word identities may be more modality-specific than often upheld.
A clinical-radiological framework of the right temporal variant of frontotemporal dementia

Abstract The concept of the right temporal variant of frontotemporal dementia (rtvFTD) is still equivocal. The syndrome accompanying predominant right anterior temporal atrophy has previously been described as memory loss, prosopagnosia, getting lost and behavioural changes. Accurate detection is challenging, as the clinical syndrome might be confused with either behavioural variant FTD (bvFTD) or Alzheimer’s disease. Furthermore, based on neuroimaging features, the syndrome has been considered a right-sided variant of semantic variant primary progressive aphasia (svPPA). Therefore, we aimed to demarcate the clinical and neuropsychological characteristics of rtvFTD versus svPPA, bvFTD and Alzheimer’s disease. Moreover, we aimed to compare its neuroimaging profile against svPPA, which is associated with predominant left anterior temporal atrophy. Of 619 subjects with a clinical diagnosis of frontotemporal dementia or primary progressive aphasia, we included 70 subjects with a negative amyloid status in whom predominant right temporal lobar atrophy was identified based on blinded visual assessment of their initial brain MRI scans. Clinical symptoms were assessed retrospectively and compared with age- and sex-matched patients with svPPA (n = 70), bvFTD (n = 70) and Alzheimer’s disease (n = 70). Prosopagnosia, episodic memory impairment and behavioural changes such as disinhibition, apathy, compulsiveness and loss of empathy were the most common initial symptoms, whereas during the disease course, patients developed language problems such as word-finding difficulties and anomia. Distinctive symptoms of rtvFTD compared to the other groups included depression, somatic complaints, and motor/mental slowness. Aside from right temporal atrophy, the imaging pattern showed volume loss of the right ventral frontal area and the left temporal lobe, which represented a close mirror image of svPPA. Atrophy of the bilateral temporal poles and the fusiform gyrus were associated with prosopagnosia in rtvFTD. Our results highlight that rtvFTD has a unique clinical presentation. Since current diagnostic criteria do not cover specific symptoms of the rtvFTD, we propose a diagnostic tree to be used to define diagnostic criteria and call for an international validation.
BANΔIT: B’‐Factor Analysis for Drug Design and Structural Biology

The analysis of B‐factor profiles from X‐ray protein structures can be utilized for structure‐based drug design since protein mobility changes have been associated with the quality of protein‐ligand interactions. With the BANΔIT (B’‐factor analysis and ΔB’ interpretation toolkit), we have developed a JavaScript‐based browser application that provides a graphical user interface for the normalization and analysis of B’‐factor profiles. To emphasize the usability for rational drug design applications, we have analyzed a selection of crystallographic protein‐ligand complexes and have given exemplary conclusions for further drug optimization including the development of a B’‐factor‐supported pharmacophore model for SARS CoV‐2 main protease inhibitors. BANΔIT is available online at https://bandit.uni‐mainz.de. The source code can be downloaded from https://github.com/FBarthels/BANDIT.
The genetic dissection of differential growth in Plasmodium falciparum and its relationship to chloroquine drug selection

by Heather B. Reilly Plasmodium falciparum malaria is responsible for severe morbidity and mortality throughout the world. Anti-malarials used to treat malaria, such as chloroquine (CQ), exhibit increased failure and have an effect on the parasite genome potentially resulting in differences in parasite growth. Differences in erythrocytic growth rates between parasite clones affect parasite virulence (Chotivanich et al., 2000; Dondorp et al., 2005). Parasite growth is complex, composed of discrete biological steps contributing to differences in overall ‘growth. ’ To identify genes and mechanisms regulating differential growth, a series of phenotypes ranging from bulk growth (e.g. blood smears and Hxincorporation) to its nested steps (merozoite production, invasion efficiency, and cycle time) were measured in progeny of a cross between a CQ resistant and CQ sensitive parasite, Dd2 and HB3 respectively, and used in quantitative trait loci (QTL) mapping. Progeny exhibit quantitative distributions of growth in all five growth assays. Significant QTLs from the two bulk growth assays and cycle time produce a preliminary list of 167 candidate genes. An unbiased method using whole genome datasets and bioinformatics
Multiplexed Proximity Biotinylation Coupled to Mass Spectrometry for Defining Integrin Adhesion Complexes

BioID, a proximity biotinylation technique, offers a valuable approach to examine the interactions occurring within protein complexes that complements traditional protein biochemical methods. BioID has various advantages that are beneficial to the study of complexes, including an ability to detect insoluble and transient proteins. We have applied BioID to the study of integrin adhesion complexes (IACs), which are located at the junction between the plasma membrane and actin cytoskeleton. The use of multiple BioID baits enables a complex‐wide, spatial annotation of IACs, which in turn facilitates the detection of novel proximal interactors and provides insights into IAC architecture. This article describes the labeling and affinity purification of IAC‐proximal proteins and their analysis by label‐free quantitative mass spectrometry. The article also outlines steps to identify high‐confidence proximity interactors, and to interrogate the topology and functional relevance of proximity interaction networks through bioinformatic analyses. © 2020 The Authors.
Construction of a middle fragment-deleted class II molecule transactivator mutant by modified OE-PCR technique

Objective:To develop a simple and efficient method for constructing a middle fragment-deleted mutant of MHC class Ⅱ molecule transactivator(CⅡTA)mutant with the 109~(th)to 226~(th) amino acid codons deleted.Methods: Two gene fragments at each end of the deleted CⅡTA gene were obtained by OE-PCR method and were mixed together for 8 PCR cycles without primers to achieve effective overlapping,then 2 primers was added for amplification of the desired fragments.The amplification products were subsequently cloned into eukaryotic vector pIRES for identification.Results: A mutant of CⅡTA with the 109~(th)to 226~(th) amino acids deleted was successfully constructed.Conclusion: This modified OE-PCR technique overcomes some shortcomings of traditional method and is very suitable for constructing mutants with middle fragment deletion,making it worth to be popularized.
Specialized Nutritious Food Combined With Cash Transfers and Social and Behavior Change Communication to Prevent Stunting Among Children Aged 6 to 23 Months in Pakistan: Protocol for a Cluster Randomized Controlled Trial

Background In Pakistan, the prevalence of stunting in children younger than 5 years has remained above global critical levels over the past two decades, with the stunting rate being 40.2% in 2018. Children living in rural areas and in the poorest households suffer the most from stunting across the country—43.2% in rural areas and 51.4% in the lowest wealth quintile. As a continuing public health concern, it is essential that stunting prevention is a national priority in order to ensure human capital development, especially among the poorest households. Objective The primary objective of this study is to determine the effect of a medium quantity of a lipid-based nutrient supplement (LNS) combined with unconditional cash transfers and social and behavior change communication (SBCC) on reduction of stunting in children aged 6 to 23 months. Methods A 5-arm cluster randomized controlled trial will be conducted in the district of Rahim Yar Khan in Punjab, Pakistan. The intervention packages will be (1) cash only, (2) cash with LNS, (3) cash with SBCC, and (4) cash with SBCC and LNS. The control arm will receive routine standard of care. We will enroll children at 6 months of age and follow up on a monthly basis up to 24 months of age. A total of 2000 children, 400 in each arm, will be enrolled to detect a 20% reduction in the prevalence of stunting among children aged 24 months. Length, weight, food intake, compliance to interventions, morbidities, and other relevant data will be collected at enrollment and on a monthly basis over the period of 18 months. The process evaluation will assess acceptability of the interventions and potential barriers to implementation through focus group discussions and in-depth interviews with the target population and relevant stakeholders. Furthermore, a cost analysis will be conducted to assess the cost-effectiveness of each intervention package. Results The study protocol was approved by the Ethics Review Committee of Aga Khan University in Pakistan on January 4, 2017. Data collection began in May 2017 and was completed in July 2019. Data analyses are yet to be completed. This study will explore the effectiveness of intervention packages comprised of cash transfers from Benazir Income Support Programme with or without additional LNS and SBCC in preventing childhood stunting. We expect the results to be published in peer-reviewed journals by autumn of 2020. Conclusions The findings of this trial will provide robust evidence as to which intervention packages can have significant effects on linear growth of children and design effective intervention packages to prevent stunting in children aged 6 to 23 months. Trial Registration ClinicalTrials.gov NCT03299218; https://clinicaltrials.gov/ct2/show/NCT03299218 International Registered Report Identifier (IRRID) DERR1-10.2196/19001
Prediction, pattern recognition and modelling of complications post-endovascular infra renal aneurysm repair by artificial intelligence

Objectives The study evaluates the plausibility and applicability of prediction, pattern recognition and modelling of complications post-endovascular aneurysm repair (EVAR) by artificial intelligence for more accurate surveillance in practice. Methods A single-centre prospective data collection on (n = 250) EVAR cases with n = 26 preoperative attributes (factors) on endpoint of endoleak (types I–VI), occlusion, migration and mortality over a 13-year period was conducted. In addition to the traditional statistical analysis, data was subjected to machine learning algorithm through artificial neural network. The predictive accuracy (specificity and –1 sensitivity) on each endpoint is presented with percentage and receiver operative curve. The pattern recognition and model classification were conducted using discriminate analysis, decision tree, logistic regression, naive Bayes and support vector machines, and the best fit model was deployed for pattern recognition and modelling. Results The accuracy of the training, validation and predictive ability of artificial neural network in detection of endoleak type I was 95, 96 and 94%, type II (94, 83, 90 and 82%) and type III was 96, 94 and 96%, respectively. Endpoints are associated with increase in weights through predictive modeling that were not detected through statistical analytics. The overall accuracy of the model was >86%. Conclusion The study highlights the applicability, accuracy and reliability of artificial intelligence in the detection of adverse outcomes post-EVAR for an accurate surveillance stratification.
Antihypertensive Drugs and Risk of Depression

Hypertension, cardiovascular diseases, and cerebrovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with antihypertensive agents decreases or increases this risk. The effects of individual drugs are also unknown. We used Danish population-based registers to systematically investigate whether the 41 most used individual antihypertensive drugs were associated with an altered risk of incident depression. Analyses of diuretics were included for comparisons. Participants were included in the study in January 2005 and followed until December 2015. Two different outcome measures were included: (1) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and (2) a combined measure of a diagnosis of depression or use of antidepressants. Continued use of classes of angiotensin agents, calcium antagonists, and β-blockers was associated with significantly decreased rates of depression, whereas diuretic use was not. Individual drugs associated with decreased depression included 2 of 16 angiotensin agents: enalapril and ramipril; 3 of 10 calcium antagonists: amlodipine, verapamil, and verapamil combinations; and 4 of 15 β-blockers: propranolol, atenolol, bisoprolol, and carvedilol. No drug was associated with an increased risk of depression. In conclusion, real-life population-based data suggest a positive effect of continued use of 9 individual antihypertensive agents. This evidence should be used in guiding prescriptions for patients at risk of developing depression including those with prior depression or anxiety and patients with a family history of depression.
Predicament Of Doctors; Discerning Burnout Level Amongst Surgical Residents Of Karachi, Pakistan.

BACKGROUND Stress and burnout have been soaring among doctors. It does not only have deleterious effects during working hours but also impact personal lives of the doctors. The primary focus of this study is to gauge level of burnout among surgical residents working in two major tertiary care hospital of Karachi, Pakistan. METHODS This was a cross sectional study comprising of 118 candidates who completed the questionnaire based on demographics variables, professional details and Maslach Burnout Inventory (MBI), which scores the burnout level on the basis of three components namely emotional exhaustion, depersonalization and personal accomplishment. The duration of study was one month starting from 1st January to 31st January 2019. Residents working in Department of General Surgery were part of inclusion criteria. Consultants and medical students met the exclusion criteria. Data was analysed by SPSS-23. RESULTS Mean MBI score was 57.15 with mean scores of Emotional Fatigue, Personal Fulfilment and Depersonalization were 22.42, 19.89 and 14.81 respectively. In terms of emotional fatigue, female residents (49.2%) were more likely to suffer than their male counterpart (50.8%) (p=0.018). Married residents (37.3%) tend to have higher mean personal fulfilment scores (p=0.02). Residents who were living alone (31%) have higher mean depersonalization score (p=0.02). With respect to personal factors, higher MBI scores were observed among doctors who were married, worked about 75-90 hours and remain sleep-deprived and those who were not able to sustain their families financially. CONCLUSIONS On the basis of higher MBI scores in married, sleep deprived residents who were working for extensive hours and felt financial constraints, there is an extensive need of comprehensive support groups, humane number of working hours, improved salary packages, de-stressing activities like sports etc. to ameliorate the mental health of resident physicians and enhance their productivity.
Clonality and cycling status of leukemic progenitors from patients with acute myeloid leukemia (AML)

We have detected a high concentration of cytogenetically normal long term culture-initiating cells (LTC-IC) in the peripheral blood (PB) of 12 patients with newly-diagnosed AML. To determine if these progenitors originated from normal polyclonal hematopoiesis the PCR-based human androgen receptor allele (HUMARA) assay was used to study PB cells from 5 female patients with cytogenetically abnormal AML. In 4/5 samples cytogenetics and clonality data from LTC indicate that a substantial number of normal polyclonal hematopoietic progenitors often persist in A M L PB at diagnosis. However, the fifth A M L sample contrasted with the others since the HUMARA assay demonstrated that LTC-derived colonies were predominantly clonal although the majority of the progenitors were cytogenetically normal. Thus, it appears that the abnormality detected on routine cytogenetics is not a reliable marker of the leukemic clone in this case. The second goal of this thesis was to characterize cycling status of different leukemic progenitors. An overnight H-thymidine (H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in CFC, LTC-IC and NOD/SCID mouse leukemia initiating cell (NOD/SL-IC) assays from the peripheral blood of 15 patients with newly-diagnosed AML. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC from the 15 samples as well as cytogenetically normal LTC-IC detected were actively cycling. However, the same assay has demonstrated that some A M L LTC-IC and most NOD/SL-IC were largely quiescent. The growth factor responsiveness of quiescent A M L cells was then studied and their functional properties compared to those of AML cells in active cell cycle. Hoechst 33342/Pyronin Y staining and FACS sorting were used to isolate Go cells in from the Gi and S/G2+M subpopulations of peripheral blood cells from 4 newly diagnosed A M L patients. Go