Miracle-dz/UniFAR-FTUs huggingface dataset:
A pharmacoeconomic evaluation of the pharmacotherapeutic options for painful diabetic neuropathy

ABSTRACT Introduction Painful diabetic neuropathy (PDN) is a high incidence and severe complication of diabetes mellitus, significantly compromising patients’ quality of life and causing tremendous economic burden. Considering drug costs becomes part of treatment decisions, with the growing choice of monotherapy or combination treatment strategies for PDN treatment. Areas covered This systematic review aims to identify the cost-effectiveness of pharmacotherapies in PDN, summarize key findings, and assess the quality of studies to inform healthcare resource allocation decisions and future research. Economic evaluations were identified by searching PubMed, Web of Science, Scopus and health technology assessment (HTA) databases, as well as screening reference lists of previously identified studies. Relevant data was extracted, and the CHEERS checklist was used to assess the quality of the studies. Expert opinion Collectively, the findings indicate that more pharmacoeconomics research is urgently needed to directly compare high-quality research for PDN combination medication/sequential treatment, and which is performed from a societal perspective. Simultaneously, to strengthen the reliability of the analysis, metrics such as adherence, incidence of adverse drug reactions, and pain levels utility value should be examined to verify the robustness of the basic results.
A Fully Convolutional Network (FCN) based Automated Ischemic Stroke Segment Method using Chemical Exchange Saturation Transfer Imaging.

BACKGROUND Chemical exchange saturation transfer (CEST) MRI is a promising imaging modality in ischemic stroke detection for its sensitivity in sensing post-ischemic pH alteration. However, the accurate segmentation of pH-altered regions remains difficult due to the complicated sources in water signal changes of CEST MRI. Meanwhile, manual localization and quantification of stroke lesions are laborious and time-consuming, which cannot meet the urgent need for timely therapeutic interventions. PURPOSE The goal of this study was to develop an automatic lesion segmentation approach of ischemic region based on CEST MR images. A novel segmentation framework based on fully convolutional neural network was investigated for our task. METHODS Z-spectra from 10 rats were manually labeled as ground truth and split into two datasets, where the training dataset including 3 rats was used to generate a segmentation model, and the remaining rats were used as test datasets to evaluate the model's performance. Then a 1-D fully convolutional neural network equipped with bottleneck structures was set up, and a Grad-CAM approach was used to produce a coarse localization map, which can reflect the relevancy to the 'ischemia' class of each pixel. RESULTS As compared with the ground truth, the proposed network model achieved satisfying segmentation results with high values of evaluation metrics including specificity (SPE), sensitivity (SEN), accuracy (ACC), and Dice similarity coefficient (DSC), especially in some intractable situations where conventional MRI modalities and CEST quantitative method failed to distinguish between ischemic and normal tissues, and the model with augmentation was robust to input perturbations. The Grad-CAM maps performed clear tissue change distributions and interpreted the segmentations, and showed a strong correlation with the quantitative method, gave extended thinking to the function of networks. CONCLUSIONS The proposed method can segment ischemia region from CEST images, with the Grad-CAM maps give access to interpretative information about the segmentations, which demonstrates great potential in clinical routines. This article is protected by copyright. All rights reserved.
Ambulatory blood pressure and hypertension control in children with autosomal recessive polycystic kidney disease: clinical experience from two central European tertiary centres

Objective : Arterial hypertension is a common complication in patients with autosomal recessive polycystic kidney disease (ARPKD), occurring in 33–75% of children when measured by office blood pressure (OBP). Ambulatory blood pressure monitoring (ABPM) is a superior tool for investigating blood pressure relative to OBP. The aim of our study was to investigate the prevalence and control of hypertension in children with ARPKD based on ABPM. Methods: This retrospective study evaluated 36 children with ARPKD and at least one ABPM performed in two our tertiary paediatric nephrology centres and 29 children with at least two ABPM. Ambulatory hypertension was defined as mean daytime or night-time BP at least 95th percentile or use of antihypertensives and controlled hypertension as normal ambulatory BP in children on antihypertensive drugs. Results: The first ABPM study revealed ambulatory hypertension in 94% of children. Untreated or uncontrolled ambulatory hypertension was diagnosed in 67% and controlled hypertension in only 28%. Masked hypertension was found in 5.5% and white-coat hypertension in 14%. The last ABPM study revealed ambulatory hypertension in 86% (all 86% hypertensive children on drugs, i.e. no untreated hypertension), the prevalence of controlled hypertension increased to 59%. Masked hypertension was detected in 8.3% and white-coat hypertension in 10%. Ambulatory blood pressure correlated neither with kidney length nor with glomerular filtration rate. Echocardiography demonstrated left ventricular hypertrophy (LVH) in 27% of children at the time of their first ABPM. Conclusion: The prevalence of ambulatory hypertension is very high in children with ARPKD, while the control of hypertension improves over time.
Distributed Fault-Tolerant Formation Tracking Control for Multiagent Systems With Multiple Leaders and Constrained Actuators

The distributed formation tracking control problem with multiple leaders under actuator faults and constraints is investigated in this article. All followers in the multiagent system should achieve a desired time-varying formation and track the convex combination of multiple leaders. To accomplish the control task, an active reconfigurable control scheme is proposed using the local information between agents, as well as the fault values of individuals provided by fault estimation observers. Combining with the Lyapunov stability theorem and the property of the Laplacian matrix, the control gains are calculated using the adaptive technique with a formation tracking feasibility condition. The original reconfigurable protocol is modified by utilizing anti-windup compensators to against saturation phenomenons (both magnitude and rate) in actuators. The simulation results validate that the presented scheme can address the faults as well as the actuator saturation.
A stress-associated protein OsSAP8 modulates gibberellic acid biosynthesis by reducing the promotive effect of transcription factor OsbZIP58 on OsKO2.

Gibberellic acid (GA) is a vital phytohormone for plant growth and development. GA biosynthesis is a complex pathway regulated by various transcription factors. Here we report a stress-associated protein OsSAP8 negatively involved in GA biosynthesis. Overexpression of OsSAP8 in rice resulted in a semi-dwarfism phenotype and reduced endogenous GA3 content. By contrast, higher endogenous GA3 content and slightly higher plant height were observed in OsSAP8 knockout mutant. Subcellular localization analysis of OsSAP8 showed it could enter into nucleus. Based on electrophoretic mobility shift assay and yeast one hybrid experiment, OsSAP8 could bind to cis-acting regulatory element GADOWNAT of ent-kaurene oxidases (KO2, KO3, KO5). The results from dual-luciferase reporter assays showed OsSAP8 doesn't activate LUC reporter gene expression. However, it could interact with OsbZIP58, which has strong transcriptional activation potential on OsKO2. Moreover, the interaction between OsSAP8, OsLOL1, and OsbZIP58 could reduce the promotive effect of transcription factor OsbZIP58 on OsKO2. These results provide some new clues on the regulation of GA biosynthesis in rice.
Clinical Applications of 4D Flow MRI in the Portal Venous System

Evaluation of the hemodynamics in the portal venous system plays an essential role in many hepatic pathologies. Changes in portal flow and vessel morphology are often indicative of disease.Routinely used imaging modalities, such as CT, ultrasound, invasive angiography, and MRI, often focus on either hemodynamics or anatomical imaging. In contrast, 4D flow MRI facilitiates a more comprehensive understanding of pathophysiological mechanisms by simultaneously and noninvasively acquiring time-resolved flow and anatomical information in a 3D imaging volume. Though promising, 4D flow MRI in the portal venous system is especially challenging due to small vessel calibers, slow flow velocities, and breathing motion. In this review article, we will discuss how to account for these challenges when planning and conducting 4D flow MRI acquisitions in the upper abdomen. We will address patient preparation, sequence acquisition, postprocessing, quality control, and analysis of 4D flow data. In the second part of this article, we will review potential clinical applications of 4D flow MRI in the portal venous system. The most promising area for clinical utilization is the diagnosis and grading of liver cirrhosis and its complications. Relevant parameters acquired by 4D flow MRI include the detection of reduced or reversed flow in the portal venous system, characterization of portosystemic collaterals, and impaired response to a meal challenge. In patients with cirrhosis, 4D flow MRI has the potential to address the major unmet need of noninvasive detection of gastroesophageal varices at high risk for bleeding. This could replace many unnecessary, purely diagnostic, and invasive esophagogastroduodenoscopy procedures, thereby improving patient compliance with follow-up. Moreover, 4D flow MRI offers unique insights and added value for surgical planning and follow-up of multiple hepatic interventions, including transjugular intrahepatic portosystemic shunts, liver transplantation, and hepatic disease in children. Lastly, we will discuss the path to clinical implementation and remaining challenges.
Guidance in selecting analytical techniques for identification and quantification of non-intentionally added substances (NIAS) in food contact materials (FCMS)

ABSTRACT There are numerous approaches and methodologies for assessing the identity and quantities of non-intentionally added substances (NIAS) in food contact materials (FCMs). They can give different results and it can be difficult to make meaningful comparisons. The initial approach was to attempt to prepare a prescriptive methodology but as this proved impossible; this paper develops guidelines that need to be taken into consideration when assessing NIAS. Different approaches to analysing NIAS in FCMs are reviewed and compared. The approaches for preparing the sample for analysis, recommended procedures for screening, identification, and quantification of NIAS as well as the reporting requirements are outlined. Different analytical equipment and procedures are compared. Limitations of today’s capabilities are raised along with some research needs.
What Is Healthy Eating? Exploring Profiles of Intuitive Eating and Nutritionally Healthy Eating in College Women

Purpose Research suggests that food’s nutritional content and the feelings and behaviors associated with eating contribute to overall health, yet these constructs are rarely considered simultaneously. The current cross-sectional study investigated healthy eating profiles in college women that included both nutritional quality and intuitive eating (IE), with IE being an eating style that prioritizes physiological hunger/satiety cues and minimizes dieting and emotional eating. Design/Setting/Subjects Undergraduate women (n = 352) completed an online assessment and daily diaries (80% retention). Measures Nutritionally healthy eating, IE, dieting, body dissatisfaction, disordered eating, and psychological health were examined. Analysis Latent profile analysis explored patterns of nutritionally healthy eating and IE, and determined how these patterns related to psychological and disordered eating outcomes. Results A four-profile solution emerged: 1) Dieting (high nutritionally healthy eating + intermediate IE), 2) Unhealthy Eating (low nutritionally healthy eating + low IE), 3) Intuitive Eating (moderately high nutritionally healthy eating + high IE), and 4) Non-Dieting (low nutritionally healthy eating + intermediate IE). These profiles significantly differed from one another, such that the Intuitive Eating and Non-Dieting profiles reported lower psychological distress, body mass index, and disordered eating compared to other profiles, while the Dieting and Unhealthy Eating profiles showed the healthiest and poorest nutritional eating, respectively. Conclusion These findings suggest that IE and nutritionally healthy eating are distinct factors in conceptualizing the eating patterns of college women, and both should be considered when developing interventions. Future research should replicate these findings in larger/more diverse samples and examine eating profiles longitudinally.
LRET-derived HADDOCK structural models describe the conformational heterogeneity required for DNA cleavage by the Mre11-Rad50 DNA damage repair complex

The Mre11-Rad50-Nbs1 protein complex is one of the first responders to DNA double-strand breaks. Studies have shown that the catalytic activities of the evolutionarily conserved Mre11-Rad50 (MR) core complex depend on an ATP-dependent global conformational change that takes the macromolecule from an open, extended structure in the absence of ATP to a closed, globular structure when ATP is bound. We have previously identified an additional ‘partially open’ conformation using luminescence resonance energy transfer (LRET) experiments. Here, a combination of LRET and the molecular docking program HADDOCK was used to further investigate this partially open state and identify three conformations of MR in solution: closed, partially open, and open, which are in addition to the extended, apo conformation. Mutants disrupting specific Mre11-Rad50 interactions within each conformation were used in nuclease activity assays on a variety of DNA substrates to help put the three states into a functional perspective. LRET data collected on MR bound to DNA demonstrate that the three conformations also exist when nuclease substrates are bound. These models were further supported with small-angle X-ray scattering data, which corroborate the presence of multiple states in solution. Together, the data suggest a mechanism for the nuclease activity of the MR complex along the DNA.
A widely distributed phosphate-insensitive phosphatase presents a route for rapid organophosphorus remineralization in the biosphere

Significance At several locations across the globe, terrestrial and marine primary production, which underpin global food security, biodiversity, and climate regulation, are limited by inorganic phosphate availability. A major fraction of the total phosphorus pool exists in organic form, requiring mineralization to phosphate by enzymes known as phosphatases prior to incorporation into cellular biomolecules. Phosphatases are typically synthesized in response to phosphate depletion, assisting with phosphorus acquisition. Here, we reveal that a unique bacterial phosphatase, PafA, is widely distributed in the biosphere and has a distinct functional role in carbon acquisition, releasing phosphate as a by-product. PafA, therefore, represents an overlooked mechanism in the global phosphorus cycle and a hitherto cryptic route for the regeneration of bioavailable phosphorus in nature. The regeneration of bioavailable phosphate from immobilized organophosphorus represents a key process in the global phosphorus cycle and is facilitated by enzymes known as phosphatases. Most bacteria possess at least one of three phosphatases with broad substrate specificity, known as PhoA, PhoX, and PhoD, whose activity is optimal under alkaline conditions. The production and activity of these phosphatases is repressed by phosphate availability. Therefore, they are only fully functional when bacteria experience phosphorus-limiting growth conditions. Here, we reveal a previously overlooked phosphate-insensitive phosphatase, PafA, prevalent in Bacteroidetes, which is highly abundant in nature and represents a major route for the regeneration of environmental phosphate. Using the enzyme from Flavobacterium johnsoniae, we show that PafA is highly active toward phosphomonoesters, is fully functional in the presence of excess phosphate, and is essential for growth on phosphorylated carbohydrates as a sole carbon source. These distinct properties of PafA may expand the metabolic niche of Bacteroidetes by enabling the utilization of abundant organophosphorus substrates as C and P sources, providing a competitive advantage when inhabiting zones of high microbial activity and nutrient demand. PafA, which is constitutively synthesized by soil and marine flavobacteria, rapidly remineralizes phosphomonoesters releasing bioavailable phosphate that can be acquired by neighboring cells. The pafA gene is highly diverse in plant rhizospheres and is abundant in the global ocean, where it is expressed independently of phosphate availability. PafA therefore represents an important enzyme in the context of global biogeochemical cycling and has potential applications in sustainable agriculture.
Efficacy and safety of same‐day discharge after atrial fibrillation ablation: A systematic review and meta‐analysis

Conventionally, patients have been admitted overnight after atrial fibrillation (AF) catheter ablation. Several centers have recently adopted a same‐day discharge (SDD) protocol for patients undergoing AF catheter ablation. We aimed to systematically review the current evidence for the safety and efficacy of SDD after AF catheter ablation. A systematic search was performed in PubMed, Embase, Scopus, Web of Science, and the Cochrane library until August 21, 2021. The risk of bias was assessed with the “Methodological Index for Non‐Randomized Studies” (MINORS). The pooled efficacy rate of SDD protocol (defined as the proportion of patients discharged the same day of ablation among the patients who were planned for SDD) was calculated. Meanwhile, pooled major complication rates and early readmission or emergency department (ED) visit rates were evaluated in successful and planned SDD groups separately. Overall, 12 observational studies consisting of 18,065 catheter ablations were included, among which 7320 (40.52%) were discharged the same‐day after ablation. The pooled efficacy was 90.3% (95% confidence interval [CI] [82.7–96.0]). The major complication rates were 1.1% (95%CI [0.5–1.9]), and 0.7% (95% CI [0.0–3.1]) in planned SDD and successful SDD groups, respectively. In addition, readmission/ED visit rate were 3.0% (95%CI [0.9–6.1]), and 3.1% (95% CI [0.8–6.5]) in the same groups. There were no significant differences between planned SDD and overnight groups with respect to major complication rate (risk ratio = 0.70, 95%CI [0.35–1.42], p‐value = .369). The available data indicates that SDD after AF ablation is safe and efficient. Further prospective and randomized studies are warranted to elucidate the safety of SDD after AF ablation and develop a standardized SDD protocol.
Mouse Cre drivers: tools for studying disorders of the human female neuroendocrine-reproductive axis

Abstract Benign disorders of the human female reproductive system, such primary ovarian insufficiency and polycystic ovary syndrome are associated with infertility and recurrent miscarriage, as well as increased risk of adverse health outcomes, including cardiovascular disease and type 2 diabetes. For many of these conditions, the contributing molecular and cellular processes are poorly understood. The overarching similarities between mice and humans have rendered mouse models irreplaceable in understanding normal physiology and elucidating pathological processes that underlie disorders of the female reproductive system. The utilization of Cre-LoxP recombination technology, which allows for spatial and temporal control of gene expression, has identified the role of numerous genes in development of the female reproductive system and in processes, such as ovulation and endometrial decidualization, that are required for the establishment and maintenance of pregnancy in mammals. In this comprehensive review, we provide a detailed overview of Cre drivers with activity in the neuroendocrine-reproductive axis that have been used to study disruptions in key intracellular signaling pathways. We first summarize normal development of the hypothalamus, pituitary, ovary, and uterus, highlighting similarities and differences between mice and humans. We then describe human conditions resulting from abnormal development and/or function of the organ. Finally, we describe loss-of-function models for each Cre driver that elegantly recapitulate some key features of the human condition and are associated with impaired fertility. The examples we provide illustrate use of each Cre driver as a tool for elucidating genetic and molecular underpinnings of reproductive dysfunction. Summary of significance The creation of mouse models with conditional deletions via Cre-LoxP technology has elucidated mechanisms of human reproductive disorders. Graphical Abstract
Cost-Effectiveness of Community-to-Clinic Tailored Navigation for Colorectal Cancer Screening in an Underserved Population: Economic Evaluation Alongside a Group-Randomized Trial

Purpose Although screening for colorectal cancer (CRC) lowers mortality and morbidity and is generally cost-effective, little is known about the cost-effectiveness of screening promotion. Design Cost-effectiveness analysis alongside a group-randomized trial. Setting: Multicultural, underinsured communities in the Phoenix, Arizona, area. Subjects English- or Spanish-speaking adults who were out of compliance for CRC screening guidelines. Intervention All participants received community-based group education (GE), and the intervention group also received tailored community-to-clinic navigation (GE+TN). Measures Number of participants screened and costs of tailored navigation, clinic visits, and CRC screening tests. Analysis Incremental cost per additional person screened from the perspective of the healthcare system with bootstrapped confidence intervals. Results Community sites were recruited and randomized to GE (n = 120) and GE + TN (n = 119). Across these sites 1154 individuals were screened, 504 were eligible, and 345 attended the group education class (n = 134 GE; n = 211 GE + TN). Screening rates (26.5% GE + TN; 10.4% GE; 16.1% increase 95% CI: 7%, 23%) and costs per participant ($271 GE + TN; $167 GE; a net cost increase of $104 95% CI: $1, $189) were significantly higher in the intervention group. Incremental cost-effectiveness was $646 (95% CI: -$68, $953) per additional person screened. Conclusion Depending on the value placed on an additional person screened, the addition of community-to-clinic tailored navigation to a community-based CRC screening promotion program may be highly cost-effective.
Investigating the role of dystrophin isoform deficiency in motor function in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is caused by DMD mutations leading to dystrophin loss. Full‐length Dp427 is the primary dystrophin isoform expressed in muscle and is also expressed in the central nervous system (CNS). Two shorter isoforms, Dp140 and Dp71, are highly expressed in the CNS. While a role for Dp140 and Dp71 on DMD CNS comorbidities is well known, relationships between mutations expected to disrupt Dp140 and Dp71 and motor outcomes are not.