Miracle-dz/UniFAR-FTUs huggingface dataset:
The macula densa is worth its salt.

Ultrafiltration of plasma in the glomerulus and the subsequent absorption of water and solutes across the tubular epithelium have evolved as the fundamental processes responsible for formation of urine by the vertebrate kidney. In mammals, this filtration/absorption process is remarkable for its magnitude. The entire extracellular fluid volume is filtered through the renal glomeruli 15 times per day in humans, 50 times per day in rats, and 100 times per day in mice. Almost all the filtered salt and water is absorbed by the renal tubules, so that the volume of excreted urine is usually less than one hundredth of the filtrate volume. Whatever the evolutionary advantages of this design, it is evident that it carries inherent vulnerability: salt excretion and, therefore, maintenance of extracellular fluid volume, circulatory volume, and organ perfusion become critically dependent upon a perfect match between the rate of ultrafiltration and tubular absorption. Catastrophic salt losses and salt gains by the kidneys are prevented by a set of mechanistic interactions between filtration and absorption. Changes in filtration lead to changes in absorption, and changes in tubular transport cause changes in filtration, relationships described as glomerular-tubular balance and tubuloglomerular feedback (TGF), respectively (1, 2). Protective adjustments in the filtration/absorption match are so much a part of regulation of kidney function that massive salt losses through the kidneys — the renal equivalent of cholera — rarely occur. Just how effective these adjustments are has been recently underscored by the demonstration that genetic defects in major renal salt and fluid transporters have surprisingly small consequences for body Na balance. Even though transporters such as the Na-K-2Cl cotransporter, the NaCl cotransporter, the ClC-Kb Cl channel, aquaporin 1, and NHE3 are each responsible for the absorption of major fractions of filtered salt and water, their complete absence is fully compatible with maintenance of Na balance, albeit at a somewhat reduced level of extracel
Treatment patterns, glycemic control & bodyweight with canagliflozin 300 mg versus GLP1RAs in Type II diabetes patients.

Aim: Real-world effectiveness of canagliflozin 300 mg versus glucagon-like peptide-1 receptor agonists (GLP1RAs) was examined in patients with Type II diabetes. Patients & methods: Patients were selected from the Optum integrated database of administrative claims and electronic health record data (1 January 2013 to 31 March 2015). Results: Patients were less likely to discontinue (p < 0.0001) or switch (p = 0.0048), more likely to add-on treatment (p = 0.0314), and achieve HbA1c <8.0% (p = 0.0364) or weight loss ≥5% (p < 0.0001) with canagliflozin versus GLP1RAs over 9 months. Mean HbA1c was similar at 3-month intervals over 9 months with canagliflozin and GLP1RAs. Conclusion: Patients were less likely to discontinue or switch with canagliflozin than GLP1RA, and were more likely to add-on. Canagliflozin patients were more likely to achieve HbA1c <8.0% and weight loss ≥5% than GLP1RA patients.
Tumor-Surveillance bei chronisch entzündlichen Darmerkrankungen

Was ist neu? Empfehlungen zur Surveillance-Koloskopie Aufgrund des erhöhten Kolonkarzinomrisikos bei Patienten mit Colitis ulcerosa (CU) sowie Patienten mit Colitis bei Morbus Crohn wird die Durchführung der ersten Überwachungskoloskopie nun zwischen dem 6. und 8. Krankheitsjahr empfohlen. Danach wird durch Evaluation der individuellen Risikofaktoren eine Risikostratifizierung vorgenommen und das individuelle Surveillance-Intervall festgelegt. Bei Patienten mit einer gleichzeitig vorliegenden primär sklerosierenden Cholangitis (PSC) wird eine jährliche Kontrollkoloskopie beginnend mit Diagnosestellung empfohlen. Bei Patienten mit Pouch wird eine Pouchoskopie alle 1 bis 2 Jahre empfohlen. Tumor-Surveillance unter Immunsuppression Immunsuppressiva und Biologika senken zwar aufgrund ihrer anti-inflammatorischen Wirkung das Risiko eines Kolonkarzinoms. Gleichzeitig können extraintestinale Malignome begünstigt werden: Gesichert ist die Risikoerhöhung für die Entstehung von Basaliomen und bestimmten EBV-assoziierten Lymphomen unter Thiopurinen. Daher wird die Bestimmung des EBV-Status insbesondere bei Männern < 35 Jahren vor Einleitung einer Immunsuppression empfohlen. Anti-TNF-Antikörper hingegen erhöhen das Risiko für Melanome, die damit eine Kontraindikation für diese Therapie darstellen. Patienten unter Immunsuppression sollten jährliche Hautkrebs-Screeninguntersuchungen wahrnehmen; für Frauen ist die regelmäßige gynäkologische Vorsorge obligat.
Short- and Long-Range Mechanical and Chemical Interphases Caused by Interaction of Boehmite (γ-AlOOH) with Anhydride-Cured Epoxy Resins

Understanding the interaction between boehmite and epoxy and the formation of their interphases with different mechanical and chemical structures is crucial to predict and optimize the properties of epoxy-boehmite nanocomposites. Probing the interfacial properties with atomic force microscopy (AFM)-based methods, especially particle-matrix long-range interactions, is challenging. This is due to size limitations of various analytical methods in resolving nanoparticles and their interphases, the overlap of interphases, and the effect of buried particles that prevent the accurate interphase property measurement. Here, we develop a layered model system in which the epoxy is cured in contact with a thin layer of hydrothermally synthesized boehmite. Different microscopy methods are employed to evaluate the interfacial properties. With intermodulation atomic force microscopy (ImAFM) and amplitude dependence force spectroscopy (ADFS), which contain information about stiffness, electrostatic, and van der Waals forces, a soft interphase was detected between the epoxy and boehmite. Surface potential maps obtained by scanning Kelvin probe microscopy (SKPM) revealed another interphase about one order of magnitude larger than the mechanical interphase. The AFM-infrared spectroscopy (AFM-IR) technique reveals that the soft interphase consists of unreacted curing agent. The long-range electrical interphase is attributed to the chemical alteration of the bulk epoxy and the formation of new absorption bands.
Fatally injured drivers in Norway 2005–2015—Trends in substance use and crash characteristics

Abstract Objective: Norway introduced a “Vision Zero” strategy in 2001, using multiple approaches, aiming toward a future in which no one will be killed or seriously injured in road traffic crashes (RTCs). Official statistics show that the number of fatally injured road users has declined substantially from 341 deaths in 2000 to 117 in 2015. In-depth crash investigations of all fatal RTCs started in Norway in 2005. The aim of this study was to investigate whether fatal crash characteristics, vehicle safety features, and prevalence of drugs and/or alcohol among fatally injured drivers and riders has changed during 2005–2015, accompanying the reduction in road fatalities. Methods: Data on all car/van drivers and motorcycle/moped riders fatally injured in RTCs during 2005–2015 were extracted from Norwegian road traffic crash registries and combined with forensic toxicology data. Results: The proportion of cars and motorcycles with antilock braking systems and cars with electronic stability control, increased significantly during the study period. The prevalence of nonuse of seat belts/helmets and speeding declined among both fatally injured drivers and riders. In addition, the prevalence of alcohol declined, though no significant change in the total prevalence of other substances was noted. Conclusion: The observed changes toward more safety installations in cars and motorcycles and lower prevalence of driver-related risk factors like alcohol use, speeding, and nonuse of seat belts/helmets among fatally injured drivers/riders may have contributed to the decrease in road traffic deaths.
Impaired Retinal Vascular Reactivity in Diabetic Retinopathy as Assessed by Optical Coherence Tomography Angiography

Purpose To assess retinal vascular reactivity in healthy controls and subjects with diabetic retinopathy (DR). Methods A total of 22 healthy control eyes and 16 eyes with DR were enrolled. Images were acquired using a commercially available swept-source optical coherence tomography angiography (SS-OCTA) system. Three conditions were tested for each patient (hyperoxia, hypercapnia, and room-air) by employing a non-rebreathing apparatus that delivered appropriate gas mixtures (100% O2, 5% CO2, room air). Vessel skeleton density (VSD) and vessel diameter index (VDI) were compared between the conditions using mixed-model ANOVA adjusting for age and hypertension. Significant gas or interaction effects were followed by a Bonferroni adjusted pairwise post hoc analysis. Statistical significance was defined at P < 0.05. Results The mixed-model ANOVA of the VSD found a significant intraindividual gas effect (F[2, 70] = 20.3, P < 0.001) and intergroup effect (F[1, 35] = 6.9, P = 0.001), and interaction effects (F[2, 70] = 4.6, P = 0.03). The post hoc pairwise comparison found significant differences among all three gas conditions in the healthy controls. In the subjects with DR, there were significant differences in VSD between hyperoxic and room air, and between hyperoxic and hypercapnic conditions, but not between hypercapnic and room-air conditions. Similar results were found for VDI. Conclusions The retinal capillaries, assessed with SS-OCTA, in subjects with DR preferentially reacted to hyperoxia but not hypercapnia, while the healthy controls reacted to both. The difference in the vascular reactivity may be indicative of the underlying pathophysiology of DR.
Tensile strength and dilatational elasticity of giant sarcolemmal vesicles shed from rabbit muscle.

1. Mechanical properties of the surface membrane of skeletal muscle were determined on sarcolemmal vesicles (mean diameter, 71 microns) shed by rabbit psoas muscle swelling in 140 mM KC1 containing collagenase. 2. Vesicles were stressed by partial aspiration into parallel bore pipettes. The isotropic membrane tension so created caused an increase in membrane area which expresses itself in an elongation of the vesicle projection into the pipette. 3. For individual vesicles, a linear relationship between membrane tension and membrane area increase was found up to the point when the vesicle burst, i.e. sarcolemmal vesicles behaved as perfectly elastic structures. 4. The maximum tension sarcolemmal vesicles could sustain before bursting was 12.4 +/‐ 0.2 mN m‐1 (median +/‐ 95% confidence interval), and the corresponding fractional increase in membrane area was 0.026 +/‐ 0.005 (median +/‐ 95% confidence interval). The elastic modulus of area expansion was 490 +/‐ 88 mN m‐1 (mean +/‐ S.D.). 5. In conformity with cited comparable work on red blood cells and artificial lipid vesicles, the strength and area elasticity of the skeletal muscle membrane are considered properties of the fluid lipid matrix of the membrane and of the degree to which the bilayer is perturbed by lipid‐protein interaction.
Intrinsic Disorder-Based Emergence in Cellular Biology: Physiological and Pathological Liquid-Liquid Phase Transitions in Cells

The visible outcome of liquid-liquid phase transitions (LLPTs) in cells is the formation and disintegration of various proteinaceous membrane-less organelles (PMLOs). Although LLPTs and related PMLOs have been observed in living cells for over 200 years, the physiological functions of these transitions (also known as liquid-liquid phase separation, LLPS) are just starting to be understood. While unveiling the functionality of these transitions is important, they have come into light more recently due to the association of abnormal LLPTs with various pathological conditions. In fact, several maladies, such as various cancers, different neurodegenerative diseases, and cardiovascular diseases, are known to be associated with either aberrant LLPTs or some pathological transformations within the resultant PMLOs. Here, we will highlight both the physiological functions of cellular liquid-liquid phase transitions as well as the pathological consequences produced through both dysregulated biogenesis of PMLOs and the loss of their dynamics. We will also discuss the potential downstream toxic effects of proteins that are involved in pathological formations.
How Does the Regulatory Genome Work?

The regulatory genome controls genome activity throughout the life of an organism. This requires that complex information processing functions are encoded in, and operated by, the regulatory genome. Although much remains to be learned about how the regulatory genome works, we here discuss two cases where regulatory functions have been experimentally dissected in great detail and at the systems level, and formalized by computational logic models. Both examples derive from the sea urchin embryo, but assess two distinct organizational levels of genomic information processing. The first example shows how the regulatory system of a single gene, endo16, executes logic operations through individual transcription factor binding sites and cis-regulatory modules that control the expression of this gene. The second example shows information processing at the gene regulatory network (GRN) level. The GRN controlling development of the sea urchin endomesoderm has been experimentally explored at an almost complete level. A Boolean logic model of this GRN suggests that the modular logic functions encoded at the single-gene level show compositionality and suffice to account for integrated function at the network level. We discuss these examples both from a biological-experimental point of view and from a computer science-informational point of view, as both illuminate principles of how the regulatory genome works.
Developing and Testing Electronic Health Record-Derived Caries Indices

Caries indices, the basis of epidemiologic caries measures, are not easily obtained in clinical settings. This study’s objective was to design, test, and validate an automated program (Valid Electronic Health Record Dental Caries Indices Calculator Tool [VERDICT]) to calculate caries indices from an electronic health record (EHR). Synthetic use case scenarios and actual patient cases of primary, mixed, and permanent dentition, including decayed, missing, and filled teeth (DMFT/dmft) and tooth surfaces (DMFS/dmfs) were entered into the EHR. VERDICT measures were compared to a previously validated clinical electronic data capture (EDC) system and statistical program to calculate caries indices. Four university clinician-researchers abstracted EHR caries exam data for 45 synthetic use cases into the EDC and post-processed with SAS software creating a gold standard to compare the VERDICT-derived caries indices. Then, 2 senior researchers abstracted EHR caries exam data and calculated caries indices for 24 patients, allowing further comparisons to VERDICT indices. Agreement statistics were computed among abstractors, and discrepancies were resolved by consensus. Agreement statistics between the 2 final-phase abstractors and the VERDICT measures showed extremely high concordance: Lin’s concordance coefficients (LCCs) >0.99 for dmfs, dmft, DS, ds, DT, dt, ms, mt, FS, fs, FT, and ft; LCCs >0.95 for DMFS and DMFT; and LCCs of 0.92–0.93 for MS and MT. Caries indices, essential to developing primary health outcome measures for research, can be reliably derived from an EHR using VERDICT. Using these indices will enable population oral health management approaches and inform quality improvement efforts.
Nucleolar and Ribosomal Dysfunction—A Common Pathomechanism in Childhood Progerias?

The nucleolus organizes around the sites of transcription by RNA polymerase I (RNA Pol I). rDNA transcription by this enzyme is the key step of ribosome biogenesis and most of the assembly and maturation processes of the ribosome occur co-transcriptionally. Therefore, disturbances in rRNA transcription and processing translate to ribosomal malfunction. Nucleolar malfunction has recently been described in the classical progeria of childhood, Hutchinson–Gilford syndrome (HGPS), which is characterized by severe signs of premature aging, including atherosclerosis, alopecia, and osteoporosis. A deregulated ribosomal biogenesis with enlarged nucleoli is not only characteristic for HGPS patients, but it is also found in the fibroblasts of “normal” aging individuals. Cockayne syndrome (CS) is also characterized by signs of premature aging, including the loss of subcutaneous fat, alopecia, and cataracts. It has been shown that all genes in which a mutation causes CS, are involved in rDNA transcription by RNA Pol I. A disturbed ribosomal biogenesis affects mitochondria and translates into ribosomes with a reduced translational fidelity that causes endoplasmic reticulum (ER) stress and apoptosis. Therefore, it is speculated that disease-causing disturbances in the process of ribosomal biogenesis may be more common than hitherto anticipated.
Analysis of methylation in the c‐MYC gene in five human myeloma cell lines

Genomic alterations of the human c‐MYC gene were analysed in five human myeloma cell lines established in Kawasaki Medical School and compared with those of normal lymphocytes, Raji cells from Burkitt's lymphoma, and an Epstein‐Barr virus positive lymphoblastoid cell line (LCL). Although no structural chromosome aberrations at 8q24, the c‐MYC locus, were distinct, the mRNA level of c‐MYC in these myeloma cell lines was 30–50‐fold that in normal peripheral blood lymphocytes. Regarding the methylation of c‐MYC, DNAs of the myeloma cell lines were digested with MspI plus EcoRI or HpaII plus EcoRI, and hybridized with three genomic 32P‐labelled probes; the first, second and third exons of the human c‐MYC gene, respectively. The extent of methylation in cytosine at a single CCGG site in the third exon substantially decreased in these myeloma cell lines as compared with that in normal tonsillar B, LCL and Raji cells. No significant differences in hypomethylation between these myeloma, normal B, LCL and Raji cells was detected in the first and second exon of c‐MVC. These results suggest that the hypomethylation in the third exon of c‐MYC might be related to the enhanced expression of c‐MYC in these human myeloma cell lines.
Floor Identification Using Magnetic Field Data with Smartphone Sensors

Floor identification plays a key role in multi-story indoor positioning and localization systems. Current floor identification systems rely primarily on Wi-Fi signals and barometric pressure data. Barometric systems require installation of additional standalone sensors to perform floor identification. Wi-Fi systems, on the other hand, are vulnerable to the dynamic environment and adverse effects of path loss, shadowing, and multipath fading. In this paper, we take advantage of a pervasive magnetic field to compensate for the limitations of these systems. We employ smartphone sensors to make the proposed scheme infrastructure free and cost-effective. We use smartphone magnetic sensors to identify the floors in a multi-story building with improved accuracy. Floor identification is performed with user activities of normal walking, call listening, and phone swinging. Various machine learning techniques are leveraged to identify user activities. Extensive experiments are performed to evaluate the proposed magnetic-data-based floor identification scheme. Additionally, the impact of device heterogeneity on floor identification is investigated using Samsung Galaxy S8, LG G6, and LG G7 smartphones. Research results demonstrate that the magnetic floor identification outperforms barometric and Wi-Fi-enabled floor detection techniques. A floor change module is incorporated to further enhance the accuracy of floor identification.
Genetic and Molecular Control of Floral Organ Identity in Cereals

Grasses represent a major family of monocots comprising mostly cereals. When compared to their eudicot counterparts, cereals show a remarkable morphological diversity. Understanding the molecular basis of floral organ identity and inflorescence development is crucial to gain insight into the grain development for yield improvement purposes in cereals, however, the exact genetic mechanism of floral organogenesis remains elusive due to their complex inflorescence architecture. Extensive molecular analyses of Arabidopsis and other plant genera and species have established the ABCDE floral organ identity model. According to this model, hierarchical combinatorial activities of A, B, C, D, and E classes of homeotic genes regulate the identity of different floral organs with partial conservation and partial diversification between eudicots and cereals. Here, we review the developmental role of A, B, C, D, and E gene classes and explore the recent advances in understanding the floral development and subsequent organ specification in major cereals with reference to model plants. Furthermore, we discuss the evolutionary relationships among known floral organ identity genes. This comparative overview of floral developmental genes and associated regulatory factors, within and between species, will provide a thorough understanding of underlying complex genetic and molecular control of flower development and floral organ identity, which can be helpful to devise innovative strategies for grain yield improvement in cereals.
Impulse control disorders in Parkinson’s disease: A systematic review on the psychometric properties of the existing measures

Background A significant percentage of patients suffering from Parkinson’s Disease (PD) experience Impulse Control Disorders (ICDs), contributing to reduced quality of life. As they can be managed by reducing the dopamine dosage, the detection of their presence is crucial for PD treatment plan. Nevertheless, they tend to be under-recognized in clinical practice, since routine screening is not common–despite existing instruments that may support clinicians. This work presents a systematic review on the psychometric properties of instruments measuring ICDs in PD, to test whether clinicians dispose of valid tools that may help them in clinical assessment. Method A systematic literature search in three databases (EMBASE, MEDLINE, and PsycINFO) was conducted. Quality of the instruments’ psychometric properties was evaluated with Terwee et al.’s criteria, and methodological quality of the studies was evaluated with the COSMIN Checklist. Results Ten studies examining seven instruments were selected. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) and the Ardouin Scale of Behavior in Parkinson’s Disease (ASBPD) resulted to be the best from a psychometric point of view. Conclusions Though the gold standard for diagnosis remains a detailed diagnostic interview, this review will encourage clinicians to use validated tools to accurately assess ICDs.
Ablative Verfahren in der Therapie von Lebermetastasen

Zusammenfassung Wenn keine extrahepatischen Metastasen vorliegen, kann ein verbessertes Überleben mit chirurgischen und interventionellen Techniken erreicht werden. Interventionelle Techniken sind entweder definiert als perkutane oder intraoperative Laparoskopie bzw. die Anwendung von thermischer Ablation. In diesem Review konzentrieren wir uns hierbei auf die beiden etablierten Techniken der Radiofrequenzablation (RFA) und der Mikrowellenablation (MWA) zur Therapie von kolorektalen Lebermetastasen. Diese beiden Techniken erlauben eine sichere Ablation von Metastasen bis zu 3 cm Größe und haben eine niedrige Komplikationsrate. In aktuellen Leitlinien haben beide Therapien ihren Stellenwert. Im Falle von schwierig zu resezierenden Metastasen stellen sie eine gute Alternative dar. Weiterhin können sie in Kombination mit Chirurgie eingesetzt werden, um das chirurgische Trauma zu reduzieren. Bei Rezidivmetastasen kann die Durchführung einer Intervention aufgrund des operativen Traumas niedrigere Morbidität für den Patienten bedeuten. Darüber hinaus sind die interventionellen Verfahren in Kombination mit einer systemischen Therapie der alleinigen Chemotherapie überlegen.