Miracle-dz/UniFAR-FTUs huggingface dataset:
Shedding of Cryptosporidium in calves and dams: evidence of re-infection and shedding of different gp60 subtypes

Abstract One of the most common causes of calf diarrhoea is the parasite Cryptosporidium parvum. Two longitudinal studies were carried out on a dairy farm Scotland to determine the prevalence of Cryptosporidium species and subtypes in a group of calves and to determine whether dams were a possible source of calfhood infection. Fecal samples were collected from 25 calves from birth to 12 months in the first year. In the second year, fecal samples were collected from pregnant cows (n = 29) and their calves (n = 30) from birth to 6 months. The samples were tested for Cryptosporidium and speciated. Cryptosporidium parvum-positive samples were subtyped by GP60 fragment analysis. All calves in both studies shed Cryptosporidium during the study period. Cryptosporidium parvum was the predominant species detected in calves ⩽6 weeks of age and at 6 months of age, C. bovis and C. ryanae were detected in calves older than 4 weeks of age but ⩽6 months of age. The prevalence of Cryptosporidium was higher in younger animals than in older animals. GP60 subtyping revealed two subtypes in calves on this farm (IIaA15G2R1 and IIaA19G2R1) that differed in frequency by age. Adult cattle also shed C. parvum, of four gp60 genotypes.
A journey through follow‐up for neurodevelopmentally at‐risk infants—A qualitative study on views of parents and professionals in Liverpool

Abstract Background With improving neonatal intensive care, more preterm babies or those with hypoxic‐ischaemic encephalopathy are surviving the newborn period. These babies are at high risk of neurodevelopmental delay. No studies to date have looked at the views of parents and professionals in relation to the processes of follow‐up for these infants. Methods We conducted a qualitative study in order to understand the views of parents of preterm babies or those with hypoxic‐ischaemic encephalopathy as well as the views of professionals who manage and support these families. Parents were recruited through general neonatal follow‐up clinics, neonatal nurse liaison services and community child health clinics and professionals through the neonatal unit and neurodevelopmental paediatrics services. We conducted in‐depth interviews using an open‐ended topic guide, which were audio recorded, transcribed and coded. We conducted a thematic content analysis where themes were inductively highlighted and grouped by consensus in order to conclude on major themes and subthemes. Results Three major themes were identified for parents and professionals. These were the following: (a) What is the future, (b) What is the journey and (c) Who can help me? Parents wanted better information earlier about the prognosis and diagnoses through face to face, honest consultations with follow‐up information available on the Internet. The most important requirements for follow‐up clinics were honesty, reassurance, consistent pathways of follow‐up and the need for a lead professional in the process. Alongside the follow‐up process, there was a need for support groups and psychological support Conclusions This study highlights the desire by parents for early information on the likely long‐term outlook for their babies but the need to ensure that the information and support, which is given, is provided appropriately and with consideration in order to provide the best care of the whole family.
Sliding mode position/force control for motion synchronization of a flexible-joint manipulator system with time delay

A robust adaptive control strategy based on a sliding mode is designed for the motion synchronization of multiple flexible-joint robotic manipulators system with time delay. First, synchronization motion of the system is considered as constraint conditions and is simplified to the position/force control. Then the time delay is considered as a first-order and compensated by the controller. By utilizing a sliding mode consisting of position error and force error, an adaptive controller based on back stepping is designed to drive the closed-loop system states to reach the adopted sliding model surface, thus can guarantee the asymptotic convergence of the position error and force error. For uncertainties of the manipulator parameters, joint stiffness and actuator inertia, an adaptive control law and robust control is applied to the online parameter estimation and bound compensation respectively. Finally, the simulation results show the feasibility of the proposed method.
Distinct Regioselectivity of Fungal P450 Enzymes for Steroidal Hydroxylation

The steroidal hydroxylases CYP5150AP3 and CYP5150AN1 together with the previously characterized CYP5150AP2 belong to the CYP5150A family of P450 enzymes with high amino acid sequence identity, but they showed completely different regioselectivities toward 11-deoxycortisol, suggesting the regioselectivity diversity of steroidal hydroxylases of CYP5150 family. They are also distinct from the known bacterial and fungal steroidal hydroxylases in substrate specificity and regioselectivity. Biocatalytic hydroxylation is one of the important transformations for the functionalization of steroid nucleus rings but remains a very challenging task in organic synthesis. These hydroxylases are useful additions to the toolbox of hydroxylase enzymes for the functionalization of steroids at various positions. ABSTRACT In this study, we identified two P450 enzymes (CYP5150AP3 and CYP5150AN1) from Thanatephorus cucumeris NBRC 6298 by combination of transcriptome sequencing and heterologous expression in Pichia pastoris. The biotransformation of 11-deoxycortisol and testosterone by Pichia pastoris whole cells coexpressing the cyp5150ap3 and por genes demonstrated that the CYP5150AP3 enzyme possessed steroidal 7β-hydroxylase activities toward these substrates, and the regioselectivity was dependent on the structures of steroidal compounds. CYP5150AN1 catalyzed the 2β-hydroxylation of 11-deoxycortisol. It is interesting that they display different regioselectivity of hydroxylation from that of their isoenzyme, CYP5150AP2, which possesses 19- and 11β-hydroxylase activities. IMPORTANCE The steroidal hydroxylases CYP5150AP3 and CYP5150AN1 together with the previously characterized CYP5150AP2 belong to the CYP5150A family of P450 enzymes with high amino acid sequence identity, but they showed completely different regioselectivities toward 11-deoxycortisol, suggesting the regioselectivity diversity of steroidal hydroxylases of CYP5150 family. They are also distinct from the known bacterial and fungal steroidal hydroxylases in substrate specificity and regioselectivity. Biocatalytic hydroxylation is one of the important transformations for the functionalization of steroid nucleus rings but remains a very challenging task in organic synthesis. These hydroxylases are useful additions to the toolbox of hydroxylase enzymes for the functionalization of steroids at various positions.
Performance Analysis of Wireless Information Surveillance in Machine-Type Communication at Finite Blocklength Regime

The Internet of Things (IoT) will feature pervasive sensing and control capabilities via the massive deployment of machine-type communication devices in order to greatly improve daily life. However, machine-type communications can be illegally used (e.g., by criminals or terrorists) which is difficult to monitor, and thus presents new security challenges. The information exchanged in machine-type communications is usually transmitted in short packets. Thus, this paper investigates a legitimate surveillance system via proactive eavesdropping at finite blocklength regime. Under the finite blocklength regime, we analyze the channel coding rate of the eavesdropping link and the suspicious link. We find that the legitimate monitor can still eavesdrop the information sent by the suspicious transmitter as the blocklength decreases, even when the eavesdropping is failed under the Shannon capacity regime. Moreover, we define a metric called the effective eavesdropping rate and study the monotonicity. From the analysis of monotonicity, the existence of a maximum effective eavesdropping rate for a moderate or even high signal-to-noise (SNR) is verified. Finally, numerical results are provided and discussed. In the simulation, we also find that the maximum effective eavesdropping rate slowly increases with the blocklength.
Cooperation among Gastroenterological, Pathological and Microbiological Departments Is Needed to Avoid the Misdiagnosis of Intestinal Tuberculosis as Inflammatory Bowel Disease

To the Editor We read with great interest the article entitled, “Ten Cases of Intestinal Tuberculosis, which were Initially Misdiagnosed as Inflammatory Bowel Disease” by Sato et al. in Intern Med Advance publication 2019; 236118 (1). This retrospective descriptive research revealed important issues related to two different diseases, specifically intestinal tuberculosis and inflammatory bowel disease, which have a similar presentation but different treatment approaches. It would be useful to inform all gastroenterologists in Japan, which has a moderate prevalence of tuberculosis (13.3/100,000), of this extremely important clinical fact (2). Criticism of the gastroenterologists who initially misdiagnose these cases should be avoided because the most important point is how to distinguish intestinal tuberculosis from inflammatory bowel syndrome correctly in the future. In particular, we would like to stress one additional point in the proposals, in addition to careful evaluation of both misleading X-rays and acid-fast bacilli of pathology specimens. Since pathology departments and microbiology departments usually belong to different regimentations and work independently in Japanese clinical settings, gastroenterologists have to send specimens to two different departments separately to obtain a correct diagnosis of intestinal tuberculosis. In addition, under the Japanese health insurance policy, requests between different departments are not allowed without a physician’s permission. Thus, reimbursement for pathologists who send specimens from cases of suspected tuberculosis to microbiology laboratories might be an option for obtaining a prompt diagnosis. We know that pathologic specimens are usually treated with formalin and that such treatments complicate bacterial recovery. However, new techniques, including polymerase chain reaction (PCR)based techniques such as nested PCR and real-time PCR, allow the possibility of bacterial recovery (3).
Understanding the impacts of missense mutations on structures and functions of human cancer-related genes: A preliminary computational analysis of the COSMIC Cancer Gene Census

Genomics and genome screening are proving central to the study of cancer. However, a good appreciation of the protein structures coded by cancer genes is also invaluable, especially for the understanding of functions, for assessing ligandability of potential targets, and for designing new drugs. To complement the wealth of information on the genetics of cancer in COSMIC, the most comprehensive database for cancer somatic mutations available, structural information obtained experimentally has been brought together recently in COSMIC-3D. Even where structural information is available for a gene in the Cancer Gene Census, a list of genes in COSMIC with substantial evidence supporting their impacts in cancer, this information is quite often for a single domain in a larger protein or for a single protomer in a multiprotein assembly. Here, we show that over 60% of the genes included in the Cancer Gene Census are predicted to possess multiple domains. Many are also multicomponent and membrane-associated molecular assemblies, with mutations recorded in COSMIC affecting such assemblies. However, only 469 of the gene products have a structure represented in the PDB, and of these only 87 structures have 90–100% coverage over the sequence and 69 have less than 10% coverage. As a first step to bridging gaps in our knowledge in the many cases where individual protein structures and domains are lacking, we discuss our attempts of protein structure modelling using our pipeline and investigating the effects of mutations using two of our in-house methods (SDM2 and mCSM) and identifying potential driver mutations. This allows us to begin to understand the effects of mutations not only on protein stability but also on protein-protein, protein-ligand and protein-nucleic acid interactions. In addition, we consider ways to combine the structural information with the wealth of mutation data available in COSMIC. We discuss the impacts of COSMIC missense mutations on protein structure in order to identify and assess the molecular consequences of cancer-driving mutations.
Effect of extrusion conditions on the physical properties of desi chickpea-barley extrudates, and quality attributes of their resulting flours.

In this study, response surface methodology (RSM) was used to evaluate the effect of extrusion conditions on physical properties of chickpea: barley extrudates (60:40), and the resulting protein quality of their flours. Barrel temperature (150-170°C) and moisture content (16-20%) were chosen as independent variables to generate central composite design. Hardness, expansion index, bulk density and protein quality were analyzed as responses parameters. Expansion was found to be higher at lower temperatures and higher moisture for the 60:40 chickpea: barley blend; bulk density became reduced with increased moisture; and hardness was found to increase at higher temperatures and lower moistures. The protein quality of their resulting flours was found to be greater at moisture contents higher than 16%. The composition, protein quality and functional attributes were also examined for raw and pre-cooked flours of chickpea, barley and blend at the center point of the RSM design (18% moisture, 160°C). Extrusion also lead to improved water hydration capacities and reduced viscosities for pre-cooked individual and blended flours relative to the raw. Moreover, extrusion also led to improved protein quality in the chickpea and chickpea-barley blend, but not the individual barley flour. This article is protected by copyright. All rights reserved.
Shifts in phenological mean and synchrony interact to shape competitive outcomes.

Climate change-induced phenological shifts are ubiquitous and have the potential to disrupt natural communities by changing the timing of species interactions. Shifts in first and/or mean phenological date are well documented, but recent studies indicate that shifts in synchrony (individual variation around these metrics) can be just as common. However, we know little about how both types of phenological shifts interact to affect species interactions and communities. Here, we experimentally manipulated the hatching phenologies of two competing species of larval amphibians to address this conceptual gap. Specifically, we manipulated the relative mean hatching time (early, same, or late relative to competitor) and population synchrony (high, medium, or low levels of variation around the mean) in a full 3x3 factorial design to measure independent and interactive effects of phenological mean and population phenological synchrony on competitive outcomes. Our results indicate that phenological synchrony within a population strongly influences intraspecific competition by changing the density of individuals and relative strength of early vs. late arriving individuals. Individuals from high synchrony populations competed symmetrically whereas individuals from low synchrony populations competed asymmetrically. At the community scale, shifts in population phenological synchrony interact with shifts in phenological mean to strongly affect key demographic rates (survival, biomass export, per capita mass, and emergence timing). Furthermore, changes in mean timing of species interactions altered phenological synchrony within a population at the next life stage, and phenological synchrony at one life stage altered the mean timing of the next life stage. Thus, shifts in phenological synchrony within populations can not only alter species interactions but species interactions in turn can also drive shifts in phenology. This article is protected by copyright. All rights reserved.
Suppression of Brown Adipocyte Autophagy Improves Energy Metabolism by Regulating Mitochondrial Turnover

The high abundance of mitochondria and the expression of mitochondrial uncoupling protein 1 (UCP1) confer upon brown adipose tissue (BAT) the unique capacity to convert chemical energy into heat at the expense of ATP synthesis. It was long believed that BAT is present only in infants, and so, it was not considered as a potential therapeutic target for metabolic syndrome; however, the discovery of metabolically active BAT in adult humans has re-stimulated interest in the contributions of BAT metabolic regulation and dysfunction to health and disease. Here we demonstrate that brown adipocyte autophagy plays a critical role in the regulation BAT activity and systemic energy metabolism. Mice deficient in brown adipocyte autophagy due to BAT-specific deletion of Atg7—a gene essential for autophagosome generation—maintained higher mitochondrial content due to suppression of mitochondrial clearance and exhibited improved insulin sensitivity and energy metabolism. Autophagy was upregulated in BAT of older mice compared to younger mice, suggesting its involvement in the age-dependent decline of BAT activity and metabolic rate. These findings suggest that brown adipocyte autophagy plays a crucial role in metabolism and that targeting this pathway may be a potential therapeutic strategy for metabolic syndrome.
An 18F-Labeled PSMA Ligand for PET/CT of Prostate Cancer: First-in-Humans Observational Study and Clinical Experience with 18F-JK-PSMA-7 During the First Year of Application

In preclinical trials, the recently developed tracer 2-methoxy-18F-DCFPyL (18F-JK-prostate-specific membrane antigen [PSMA]-7) has shown favorable properties regarding clinical performance and radiochemical accessibility. The aim of this study was to evaluate the clinical utility of 18F-JK-PSMA-7 for PET/CT imaging of patients with prostate cancer. Methods: In an Institutional Review Board–approved pilot study, the initial clinical utility of PET/CT imaging with 18F-JK-PSMA-7 was directly compared with 68Ga-PSMA-11 PET/CT in a group of 10 patients with prostate cancer. The 2 PSMA tracers were administered to each patient less than 3 wk apart. Next, we analyzed the data of 75 consecutive patients who had undergone clinical 18F-JK-PSMA-7 PET/CT imaging for tumor localization of biochemical recurrence (BCR). Results: The pilot study in 10 patients who were examined with both PSMA tracers demonstrated that 18F-JK-PSMA-7 was at least equivalent to 68Ga-PSMA-11. All unequivocally 68Ga-PSMA-11–positive lesions could be also detected using 18F-JK-PSMA-7, and in 4 patients additional suspected PSMA-positive lesions were identified (1 patient changed from PSMA-negative to PSMA-positive). In patients with BCR (after prostatectomy or radiotherapy), the capacity of 18F-JK-PSMA-7 PET/CT to detect at least one PSMA-positive lesion was 84.8%. The prostate-specific antigen (PSA)–stratified detection rate of 18F-JK-PSMA-7 after prostatectomy varied among 54.5% (6/11 patients; PSA < 0.5 μg/L), 87.5% (14/16 patients; PSA 0.5–2 μg/L), and 90.9% (20/22 patients; PSA > 2 μg/L). Conclusion: The tracer 18F-JK-PSMA-7 was found to be safe and clinically useful. We demonstrated that 18F-JK-PSMA-7 was not inferior when directly compared with 68Ga-PSMA-11 in a pilot study but indeed identified additional PSMA-avid suspected lesions in oligometastasized patients with BCR. In a subsequent analysis of a clinical cohort of BCR patients, 18F-JK-PSMA-7 was useful in tumor localization. 18F-JK-PSMA-7 is recommended for future prospective trials.
Use of Ambulatory Glucose Profile for Improving Monitoring and Management of T2DM.

Aim To demonstrate glycemic variability in type 2 diabetic patients and consequent control of the same. Methods 108 patients with type 2 diabetes with an HbA1c level of 7.5-8.5% were selected for the study. A Freestyle Libre Pro AGP sensor was applied to the patients after explaining the patient about the same. Next, they were called for follow up at 3rd, 7th, 11th and 14th days. Based on the readings and graph obtained, diet and treatment changes were made on various follow-up days. The sensor was removed at the end of 14 days. Results Out of the 108 subjects, 106 completed the study. There were no adverse device effects. 98 patients had therapy changes while the rest had diet and lifestyle modifications. The mean HbA1c decreased from 7.96% to 7.03% by the end of 15 days. The glycemic variability curves helped in recognizing and treating masked or asymptomatic hypoglycemic events. It also graphically shows intervals of optimal and sub-optimal glycemia. Conclusion AGP is one of the most recent, innovative developments that are being used to monitor Glycaemic variability in DM patients. AGP is generated from the Flash Glucose Monitoring device which is like a CGM device attached to the patient for a maximum period of 14 days, which checks the ISF glucose at every 15 minutes. We are able to get a Glycaemic variability curve, a median, a modal, various percentiles and statistical data generated through this. AGP study in the patient provides the doctor with an opportunity to have a complete glycemic picture of the patient l. It offers a reliable, predictive, standardized visualization of the glucose data. We were able to not only reduce the Glycaemic variability but were also able to improve their Quality of Life by reducing the frequency of hypos. The data lead to breaking of the clinical inertia and provided a valuable insight into Glycaemic patterns. The achievement of near to normal Glycaemic status at the end of 14 days reflected the use of AGP as an interventional tool.
Time-resolved volumetric MRI in MRI-guided radiotherapy: an in silico comparative analysis

MRI-treatment units enable 2D cine-MRI centred in the tumour for motion detection in radiotherapy, but they lack 3D information due to spatio-temporal limits. To derive time-resolved 3D information, different approaches have been proposed in the literature, but a rigorous comparison among these strategies has not yet been performed. The goal of this study is to quantitatively investigate five published strategies that derive time-resolved volumetric MRI in MRI-guided radiotherapy: Propagation, out-of-plane motion compensation, Fayad model, ROI-based model and Stemkens model. Comparisons were performed using an MRI digital phantom generated with six different patient-derived motion signals and tumour-shapes. An average 4D cycle was generated as well as 2D cine-MRI data with corresponding 3D in-room ground truth. Quantitative analysis was performed by comparing the estimated 3D volume to the ground truth available for each 2D cine-MRI sample. A grouped patient statistical analysis was performed to evaluate the performance of the selected methods, in case of tumour tracking or motion estimation of the whole anatomy. Analyses were also performed based on patient characteristics. Quantitative ranking of the investigated methods highlighted that Propagation and ROI-based model strategies achieved an overall median tumour centre of mass 3D distance from the ground truth of 1.1 mm and 1.3 mm, respectively, and a diaphragm distance below 1.6 mm. Higher errors and variabilities were instead obtained for other methods, which lack the ability to compensate for in-room variations and to account for regional changes. These results were especially evident when further analysing patient characteristics, where errors above 2 mm/5 mm in tumour/diaphragm were found for more irregular breathing patterns in case of out-of-plane motion compensation, Fayad and Stemkens models. These findings suggest the potential of the proposed in silico framework to develop and compare strategies to estimate time-resolved 3DMRI in MRI-guided radiotherapy.