Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Diagnostic Decision Support System for Medical Professionals: Prospective Feasibility Study

Background Continuously growing medical knowledge and the increasing amount of data make it difficult for medical professionals to keep track of all new information and to place it in the context of existing information. A variety of digital technologies and artificial intelligence–based methods are currently available as persuasive tools to empower physicians in clinical decision-making and improve health care quality. A novel diagnostic decision support system (DDSS) prototype developed by Ada Health GmbH with a focus on traceability, transparency, and usability will be examined more closely in this study. Objective The aim of this study is to test the feasibility and functionality of a novel DDSS prototype, exploring its potential and performance in identifying the underlying cause of acute dyspnea in patients at the University Hospital Basel. Methods A prospective, observational feasibility study was conducted at the emergency department (ED) and internal medicine ward of the University Hospital Basel, Switzerland. A convenience sample of 20 adult patients admitted to the ED with dyspnea as the chief complaint and a high probability of inpatient admission was selected. A study physician followed the patients admitted to the ED throughout the hospitalization without interfering with the routine clinical work. Routinely collected health-related personal data from these patients were entered into the DDSS prototype. The DDSS prototype’s resulting disease probability list was compared with the gold-standard main diagnosis provided by the treating physician. Results The DDSS presented information with high clarity and had a user-friendly, novel, and transparent interface. The DDSS prototype was not perfectly suited for the ED as case entry was time-consuming (1.5-2 hours per case). It provided accurate decision support in the clinical inpatient setting (average of cases in which the correct diagnosis was the first diagnosis listed: 6/20, 30%, SD 2.10%; average of cases in which the correct diagnosis was listed as one of the top 3: 11/20, 55%, SD 2.39%; average of cases in which the correct diagnosis was listed as one of the top 5: 14/20, 70%, SD 2.26%) in patients with dyspnea as the main presenting complaint. Conclusions The study of the feasibility and functionality of the tool was successful, with some limitations. Used in the right place, the DDSS has the potential to support physicians in their decision-making process by showing new pathways and unintentionally ignored diagnoses. The DDSS prototype had some limitations regarding the process of data input, diagnostic accuracy, and completeness of the integrated medical knowledge. The results of this study provide a basis for the tool’s further development. In addition, future studies should be conducted with the aim to overcome the current limitations of the tool and study design. Trial Registration ClinicalTrials.gov NCT04827342; https://clinicaltrials.gov/ct2/show/NCT04827342
Hyaluronan-mediated motility receptor antisense RNA 1 promotes hepatitis B virus-related hepatocellular carcinoma progression by regulating miR-627-3p/High Mobility Group AT-hook 2 axis

ABSTRACT Hepatocellular carcinoma (HCC) is a common malignancy in the world, with high mortality and poor prognosis. Hepatitis B virus (HBV) is one of the key factors implicated in the occurrence of HCC. Increasing evidence suggests that miRNAs play important roles in the development and metastasis of HBV-associated HCC (HBV-HCC). Here, we performed CCK8 (Cell count kit-8), EdU (5-ethynyl-2’-deoxyuridine) incorporation assay, wound-healing assay, transwell assay to study the changes in the cellular phenotype. Luciferase reporter assay, RNA pull-down experiment, RT-qPCR and western blotting were employed to study molecular mechanism. In addition, we also constructed a mouse HCC xenograft model to verify the functional role of HMMR-AS1/miR-627-3p/HMGA2 signal axis in vivo. Our study demonstrated that HMMR-AS1 was highly expressed in HCC tissues and cell lines, suggesting its implication in the progression of HCC. In addition, in vitro experiments showed that high HMMR-AS1 expression facilitated the migration, invasion, and proliferation of HCC cells. We further revealed that HMMR-AS1 promoted the malignant phenotype of HCC cells by regulating miR-627-3p/HMGA2 axis. Together, our data suggest that HMMR-AS1 regulates HBV-HCC progression via miR-627-3p/HMGA2 axis. GRAPHICAL ABSTRACT
Regional Cardiac Motion Scoring With Multi-Scale Motion-Based Spatial Attention

Regional cardiac motion scoring aims to classify the motion status of each myocardium segment into one of the four categories (normal, hypokinetic, akinetic, and dyskinetic) from multiple short-axis MR sequences. It is essential for prognosis and early diagnosis for various cardiac diseases. However, the complex motion procedure of the myocardium and the invisible pattern differences pose great challenges, leading to low performance for automatic methods. Most existing works mitigate the task by differentiating the normal motion patterns from the abnormal ones, without fine-grained motion scoring. We propose an effective method for the task of cardiac motion scoring by connecting a bottom-up and another top-down branch with a novel motion-based spatial attention module in multi-scale space. Specifically, we use the convolution blocks for low-level feature extraction that acts as a bottom-up mechanism, and the task of optical flow for explicit motion extraction that acts as a top-down mechanism for high-level allocation of spatial attention. To this end, a newly designed Multi-scale Motion-based Spatial Attention (MMSA) module is used as the pivot connecting the bottom-up part and the top-down part, and adaptively weight the low-level features according to the motion information. Experimental results on a newly constructed dataset of 1440 myocardium segments from 90 subjects demonstrate that the proposed MMSA can accurately analyze the regional myocardium motion, with accuracies of 79.3% for 4-way motion scoring, 89.0% for abnormality detection, and correlation of 0.943 for estimation of motion score index. This work has great potential for practical assessmentof cardiac motion function.
The effect of technological processes on contamination with B-class trichothecenes and quality of spring wheat products from grain harvested at different times

Abstract The study aimed to investigate the effect of technological processes on deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON) and 15-acetyl-deoxynivalenol (15-ADON) concentrations and quality of spring wheat products from grain harvested at different times. In this study, 408 samples were analysed for DON, 3-ADON and 15-ADON contamination by the HPLC method with UV detection. Delays in harvesting due to cool and rainy weather conditions resulted in increased DON, 3-ADON and 15-ADON levels. The highest DON concentrations were determined in bran. Higher DON concentrations in the bran indicate the protective function of the grain hull. On the other hand, the highest levels of minerals have been found in bran and whole grain flours, highlighting the importance of consuming these milling fractions as a mineral source with sustained health benefits. Our results showed that DON is stable at 170 °C, and high DON levels in whole-meal flour and white flour could not be converted or decomposed during baking. The levels of 3-ADON and 15-ADON in whole-meal flour bread and white flour bread were significantly reduced but not completely removed. The levels of DON and its derivatives 3-ADON and 15-ADON were significantly reduced in starch and gluten produced from contaminated whole meal flour; however, the washing process did not completely eliminate these toxic compounds. The concentrations of mycotoxins in starch and gluten remained relatively high. Negative correlation was found in highly contaminated samples between DON and bread baking properties. Also, inverse relationship was found between high mycotoxin concentrations and mineral element content in white flour.
Force feedback in surgery: physical constraints and haptic information

Force feedback is widely assumed to enhance performance in robotic surgery, but its benefits have not yet been systematically assessed. Further, the cost of force sensors that allow force feedback is prohibitive, due to the stringent specifications imposed by the surgical environment. We address both sides of this cost benefit analysis of force feedback by investigating the specific benefits allowed by force feedback and by proposing a novel force sensor design. We demonstrate the benefit of force feedback in surgery through a series of psychophysical experiments. By investigating performance on tasks with and without force feedback, we find that the primary benefit of force feedback is that interaction forces are reduced. This results in an increase in patient safety, because high forces correlate directly with tissue trauma. Two mechanisms enable force reduction and other benefits: (1) force feedback transforms environmental interaction forces into mechanical constraints and (2) forces act as a source of information. Mechanical constraints passively reduce intrusions into environmental structures (and, thereby, forces) due to the interactions between hand compliance and environment stiffness. Because this benefit is passive, it happens without a cognitive response. Accordingly, these benefits occur instantaneously, on the time scale of mechanical interactions. Force feedback also allows additional manipulation strategies that take advantage of these physical interactions, potentially reducing mental workload of the surgeon. We also find that force feedback provides information to the surgeon. While the number of ways that forces can potentially inform surgeons is large, the interaction between training and other sources of information is complex. We find that training is necessary, in some contexts, to take full advantage of the informational benefits of force feedback in surgery. We propose a three axis force sensor design using strain gages and Shape Deposition Manufacturing (SDM), where components are embedded inside a pourable epoxy. The resulting sensor (+/-2 N range, 0.15 RMS calibration error, 0.15 N drift over five minutes) is small enough for minimally invasive surgery, waterproof, and temperature insensitive. Adapting the SDM design for mass production is straightforward (sensors are cast inreusable molds), resulting in high performance, low cost, disposable sensors.
Activating cryptic biosynthetic gene cluster through a CRISPR–Cas12a-mediated direct cloning approach

Abstract Direct cloning of biosynthetic gene clusters (BGCs) from microbial genomes facilitates natural product-based drug discovery. Here, by combining Cas12a and the advanced features of bacterial artificial chromosome library construction, we developed a fast yet efficient in vitro platform for directly capturing large BGCs, named CAT-FISHING (CRISPR/Cas12a-mediated fast direct biosynthetic gene cluster cloning). As demonstrations, several large BGCs from different actinomycetal genomic DNA samples were efficiently captured by CAT-FISHING, the largest of which was 145 kb with 75% GC content. Furthermore, the directly cloned, 110 kb long, cryptic polyketide encoding BGC from Micromonospora sp. 181 was then heterologously expressed in a Streptomyces chassis. It turned out to be a new macrolactam compound, marinolactam A, which showed promising anticancer activity. Our results indicate that CAT-FISHING is a powerful method for complicated BGC cloning, and we believe that it would be an important asset to the entire community of natural product-based drug discovery.
ICP-MS determination of elemental abundance in traditional medicinal plants commonly used in the Kingdom of Saudi Arabia

ABSTRACT Medicinal plants are widely used in the Kingdom of Saudi Arabia to treat various ailments in the form of folk medicine. Forty four such medicinal plant samples were collected from local markets and evaluated for the presence of 14 elements (Mn, Cr, Co, Ni, Cu, Mo, Al, Pb, Ba, Zn, Ag, Hg, Bi, Cd). Microwave-assisted digestion with inductively coupled plasma-mass spectrometry (ICP-MS) was applied to determine the elemental composition in these medicinal plants. Widespread occurrence of these elements was observed in all plant samples, except for Bi and Co where the lowest mean values of 0.03 ± 0.04 and 0.03 ± 0.15 were observed, respectively. The descending order for mean (μg/g) elemental occurrence observed was as follows: Ba > Al > Zn > Ni > Mn > Ba > Hg > Mo > Cu > Cr > Ag > Cd > Co > Bi, whereas the range for these elements in the 44-medicinal plants was as follows: Pb > Al > Zn > Ni > Mn > Cu > Mo > Ag > Ba > Hg > Co > Cd > Cr > Bi. Pb, Hg and Cd were found beyond the maximum limits in these medicinal plants, while the remaining elements were found well within the range of maximum limits. A number of medicinal plants showed high amounts of these elements. Some plants contained more than one element, such as Foeniculum vulgare Mill (Pb, Hg, Cd), Ricinus communis (Pb, Cd), Vigna radiata (Pb, Cd) and Sesamum indicum (Pb, Hg). The data matrix was validated through the statistical tools of principal component analysis (X2 = 160.44, P = .00), Pearson’s correlation (P = .01 and 0.05), and K-mean cluster analysis (F = 104.55, P = .00). The findings of the study provide baseline data for the comparative analysis of these medicinal plants, which may help select safe medicinal plants in terms of consumer-based use and its utilisation for the treatment of various ailments.
Biopsy-proven CKD etiology and outcomes: the Chronic Kidney Disease Japan Cohort (CKD-JAC) study

ABSTRACT Background The Kidney Disease: Improving Global Outcomes guidelines advocate the cause–glomerular filtration rate (GFR)–albuminuria (CGA) classification for predicting outcomes. However, there is a dearth of data supporting the use of the cause of chronic kidney disease. This study aimed to address how to incorporate a prior biopsy-proven diagnosis in outcome prediction. Methods We examined the association of biopsy-proven kidney disease diagnoses with kidney failure with replacement therapy (KFRT) and all-cause death before KFRT in patients with various biopsy-proven diagnoses (n = 778, analysis A) and patients with diabetes mellitus labeled with biopsy-proven diabetic nephropathy (DN), other biopsy-proven diseases and no biopsy (n = 1117, analysis B). Results In analysis A, adding biopsy-proven diagnoses to the GFR–albuminuria (GA) classification improved the prediction of 8-year incidence of KFRT and all-cause death significantly regarding integrated discrimination improvement and net reclassification index. Fine–Gray (FG) models with KFRT as a competing event showed significantly higher subdistribution hazard ratios (SHRs) for all-cause death in nephrosclerosis {4.12 [95% confidence interval (CI) 1.11–15.2)], focal segmental glomerulosclerosis [3.77 (95% CI 1.09–13.1)]} and membranous nephropathy (MN) [2.91 (95% CI 1.02–8.30)] than in immunoglobulin A nephropathy (IgAN), while the Cox model failed to show significant associations. Crescentic glomerulonephritis had the highest risk of all-cause death [SHR 5.90 (95% CI 2.05–17.0)]. MN had a significantly lower risk of KFRT than IgAN [SHR 0.45 (95% CI 0.24–0.84)]. In analysis B, other biopsy-proven diseases had a lower risk of KFRT than biopsy-proven DN in the FG model, with death as a competing event [SHR 0.62 (95% CI 0.39–0.97)]. Conclusions The CGA classification is of greater value in predicting outcomes than the GA classification.
Population balance modelling captures host cell protein dynamics in CHO cell cultures

Monoclonal antibodies (mAbs) have been extensively studied for their wide therapeutic and research applications. Increases in mAb titre has been achieved mainly by cell culture media/feed improvement and cell line engineering to increase cell density and specific mAb productivity. However, this improvement has shifted the bottleneck to downstream purification steps. The higher accumulation of the main cell-derived impurities, host cell proteins (HCPs), in the supernatant can negatively affect product integrity and immunogenicity in addition to increasing the cost of capture and polishing steps. Mathematical modelling of bioprocess dynamics is a valuable tool to improve industrial production at fast rate and low cost. Herein, a single stage volume-based population balance model (PBM) has been built to capture Chinese hamster ovary (CHO) cell behaviour in fed-batch bioreactors. Using cell volume as the internal variable, the model captures the dynamics of mAb and HCP accumulation extracellularly under physiological and mild hypothermic culture conditions. Model-based analysis and orthogonal measurements of lactate dehydrogenase activity and double-stranded DNA concentration in the supernatant show that a significant proportion of HCPs found in the extracellular matrix is secreted by viable cells. The PBM then served as a platform for generating operating strategies that optimise antibody titre and increase cost-efficiency while minimising impurity levels.
Metabolic syndrome and its association with components of sarcopenia in older community-dwelling Chinese

Aging and obesity contribute to muscle dysfunction. This study aimed to determine the cross-sectional associations between components of metabolic syndrome (MetS) and sarcopenia in 251 older community-dwelling Chinese. The total fat-free mass was measured by dual-energy X-ray absorptiometry, muscle strength (handgrip strength) by a handheld dynamometer, physical performance by 4-meter walk, 5-time chair stand test, and the short physical performance battery (SPPB). MetS was defined using the International Diabetes Federation (IDF) criteria. The participants with MetS had a higher appendicular skeletal muscle mass (ASM) and relative ASM (RASM). The males with MetS had higher handgrip strength, and the females with MetS had higher SPPB scores. After adjusting for age and body mass index, the participants with an increased waist circumference had a higher ASM, and those with increased diastolic blood pressure (DBP) also had higher handgrip strength. The males with elevated fasting blood glucose (FBG) levels had a lower gait speed. Components of MetS, such as DPB and FBG, were associated with muscle strength and physical performance in older adults. These results suggest that muscle strength and function should be considered in treating older adults with MetS.
Can routine screening for alcohol consumption in pregnancy be ethically and legally justified?

In the UK, it has been proposed that alongside the current advice to abstain from alcohol completely in pregnancy, there should be increased screening of pregnant women for alcohol consumption in order to prevent instances of fetal alcohol spectrum disorder. The Scottish Intercollegiate Guidelines Network published guidelines in 2019 recommending that standardised screening questionnaires and associated use of biomarkers should be considered to identify alcohol exposure in pregnancy. This was followed in 2020 by the National Institute for Health and Care Excellence Draft Quality Standard, which recommended that pregnant women should have information on their alcohol consumption recorded throughout their pregnancy and this information transferred to the child’s health records. Most recently, Public Health England has stated that the alcohol intake of all women should be recorded throughout pregnancy, not just at the initial booking appointment and that tools such as blood biomarkers and meconium testing should be researched in order to determine true prevalence rates of alcohol in pregnancy. We argue that this proposed enhanced screening undermines women’s autonomy and their legal right to be sufficiently informed to consent to screening. We argue that there is no evidence that this kind of screening will result in a reduction of fetal harm and there is a danger that undermining the autonomy of women and the trust relationship between women and healthcare professionals may even increase harm to future children.
A qualitative exploration to understand barriers and facilitators to daily oral PrEP uptake and sustained adherence among HIV‐negative women planning for or with pregnancy in rural Southwestern Uganda

Antiretroviral pre‐exposure prophylaxis (PrEP) may reduce periconception and pregnancy HIV incidence among women in settings, where gender power imbalances limit HIV testing, engagement in care and HIV viral suppression. We conducted qualitative interviews to understand factors influencing periconception and pregnancy PrEP uptake and use in a cohort of women (Trial registration: NCT03832530) offered safer conception counselling in rural Southwestern Uganda, where PrEP uptake was high.
Five-gene signature predicts acute kidney injury in early kidney transplant patients

Patients with acute kidney injury (AKI) show high morbidity and mortality, and a lack of effective biomarkers increases difficulty in its early detection. Weighted gene co-expression network analysis (WGCNA) detected a total of 22 gene modules and 6 miRNA modules, of which 4 gene modules and 3 miRNA modules were phenotypically co-related. Functional analysis revealed that these modules were related to different molecular pathways, which mainly involved PI3K-Akt signaling pathway and ECM-receptor interaction. The brown modules related to transplantation mainly involved immune-related pathways. Finally, five genes with the highest AUC were used to establish a diagnosis and prediction model of AKI. The model showed a high area under curve (AUC) in the training set and validation set, and their prediction accuracy for AKI was as high as 100%. Similarly, the prediction accuracy of AKI after 24 h in the 0 h transplant sample was 100%. This study may provide new features for the diagnosis and prediction of AKI after kidney transplantation, and facilitate the diagnosis and drug development of AKI in kidney transplant patients.
Ethics Roundtable: “Organ Donation After Cardiac Death” in a Patient with Developmental Delay

JG is a 34-year-old female resident of a group home with a history of developmental delay. She has no living family and, in the past, was able to make decisions regarding meals and clothing. She was relatively healthy and never had to make any medical decisions for herself other than consenting to a feeding gastrostomy tube that was placed due to chronic aspiration 1 year ago. She still desired to eat and was known to aspirate frequently by the group home staff. On the day of admission, JG was found collapsed, comatose, and pulseless in her room. Cardiopulmonary resuscitation (CPR) was initiated, and when Emergency medical services (EMS) arrived, a large bolus of food was found occluding her airway. There was loss of pulse, which returned after IV epi-nephrine. The duration of her anoxic episode was unknown. During the next 16 days, JG did not regain consciousness. Computerized tomography (CT) of the brain without contrast was non-revealing. She was supported on mechanical venti-lation and pressors for shock. On day 12, brain death determination was considered due to loss of brain stem re ﬂ exes. On further examination, however, JG retained minimal gag and pupillary re ﬂ exes. On day 13, total loss of brain stem re ﬂ exes was reported, and a nuclear medicine brain ﬂ ow study reported, “ no cerebral perfusion