Miracle-dz/UniFAR-FTUs huggingface dataset:
Vibratory testing with the 64 Hz Rydel‐Seiffer tuning fork and its relation to the sural nerve action potential

Despite its widespread use, little is known regarding the ability of the semi‐quantitative Rydel‐Seiffer tuning fork to designate peripheral nerve function. We sought to determine in a large sample of normal and abnormal nerves the relationship between vibration sense and compound sensory nerve action potential (SNAP) parameters recorded in a corresponding innervation area. Vibratory thresholds were determined on a scale of 0 to 8 with a 64 Hz Rydel‐Seiffer tuning fork placed on the lateral malleolus of 303 subjects. Sural nerve sensory neurography was employed to derive SNAP parameters, which were related to vibration sense by means of multiple linear regression. ROC curve analysis was performed to determine the classification efficacy of the tuning fork in distinguishing normal from abnormal sural nerve responses. SNAP amplitude was the most significant predictor in the whole subjects group and in the subgroup of subjects with normal SNAPs, whereas conduction velocity played a major role in subjects with abnormal SNAPs. Age was significantly associated with vibration perception, particularly in subjects with normal SNAPs. With an area under the curve of 0.730, vibration sense was a fair classifier for decreased SNAP amplitudes. The optimal vibratory cutoff was 4.2. Age is a major determinant of vibratory test results, highlighting the importance of aging of central and peripheral pathways in mediating vibration sense. Hence, neurophysiological testing cannot be omitted in the context of polyneuropathy work‐up, since even at the optimal cutoff threshold, vibratory examination still displays 40% false negative test results.
A high-performance potassium metal battery using safe ionic liquid electrolyte

Significance Rechargeable potassium batteries are promising alternatives of Li batteries owing to the earth abundance and low cost of potassium. The safety of K metal battery involving highly reactive potassium metal and flammable organic electrolyte remains poor, risking fire hazards during use. This work presents the development of an ionic liquid electrolyte that allows safe and high-performance potassium metal batteries. An impressive capacity retention of 89% after 820 cycles is achieved with a high average Coulombic efficiency of 99.9%. Moreover, the K metal battery can safely and stably work at 60 °C. This work provides insights to future design and innovation of other metal batteries toward safe and long-life energy storage. Potassium secondary batteries are contenders of next-generation energy storage devices owing to the much higher abundance of potassium than lithium. However, safety issues and poor cycle life of K metal battery have been key bottlenecks. Here we report an ionic liquid electrolyte comprising 1-ethyl-3-methylimidazolium chloride/AlCl3/KCl/potassium bis(fluorosulfonyl) imide for safe and high-performance batteries. The electrolyte is nonflammable and exhibits a high ionic conductivity of 13.1 mS cm−1 at room temperature. A 3.6-V battery with K anode and Prussian blue/reduced graphene oxide cathode delivers a high energy and power density of 381 and 1,350 W kg−1, respectively. The battery shows an excellent cycling stability over 820 cycles, retaining ∼89% of the original capacity with high Coulombic efficiencies of ∼99.9%. High cyclability is also achieved at elevated temperatures up to 60 °C. Uniquely, robust K, Al, F, and Cl-containing passivating interphases are afforded with this electrolyte, which is key to superior battery cycling performances.
Inhibition of Prolyl-Hydroxylase Domain Enzymes Protects From Reoxygenation Injury in Engineered Human Myocardium.

Die zeitnahe Wiederherstellung der Herzdurchblutung ist die wichtigste Maßnahme, um den Schaden durch einen Herzinfarkt möglichst gering zu halten. Die Reperfusion des hypoxischen Herzmuskels kann jedoch auch zu zusätzlicher Zellschädigung im Sinne eines Reoxygenierungsschadens führen. Zentral für die Anpassung an eine Hypoxie ist das HIF1 System, das wichtige zelluläre Funktionen bei Sauerstoffmangel aufrechterhalten kann. Für die Entdeckung dieses Systems wurde 2019 der Nobelpreis für Physiologie und Medizin verliehen. In dieser Arbeit wurde der Effekt einer HIF1 stabilisierenden Substanz (Roxadustat) in einem humanen, präklinischen Modell von Herzmuskulatur, die durch Hypoxie und Reoxygenierung geschädigt wurde, getestet. Dabei zeigte eine kurzzeitige Gabe von Roxadustat im Anschluss an die Hypoxie einen protektiven Effekt vor einem Reoxygenierungsschaden mit deutlich verbesserter kontraktiler Funktion. Da sich Roxadustat bereits als Therapie der renalen Anämie im europäischen Zulassungsverfahren befindet, besteht die Hoffnung, dass die kardioprotektive Wirkung von Roxadustat zügig in eine kardioprotektive Therapie nach Herzinfarkt weiterentwickelt werden kann.
†Tugenchromis pickfordi, gen. et sp. nov., from the Upper Miocene—A Stem-Group Cichlid of the ‘East African Radiation’

ABSTRACT The highly diverse tropical freshwater fish family Cichlidae is sparsely represented in the fossil record. Here we describe the new cichlid †Tugenchromis pickfordi, gen. et sp. nov., from the Upper Miocene (9–10 Ma) of central Kenya. The new taxon possesses a unique combination of characters, including six lateral line foramina on the lacrimal, three lateral line segments, cycloid scales, and a low number of vertebrae (29), dorsal fin spines (13), and dorsal soft rays (9). Its lacrimal morphology and tripartite lateral line suggest an affinity with the present-day Lake Tanganyika tribes Ectodini and Limnochromini, and thus with members of the ‘East African Radiation’ among the African cichlids. To further elucidate the relationships of †T. pickfordi, we used a comprehensive comparative data set comprising meristic data from all present-day tribes of the ‘East African Radiation. ’ Principal coordinates analyses support links between the fossil and Ectodini + Limnochromini, and additionally with modern Haplochromini. We conclude that †T. pickfordi could be an extinct lineage within the ‘most ancient Tanganyika tribes,’ or a stem lineage of the ‘ancient Tanganyika mouthbrooders. ’ A direct relationship to the Haplochromini is unlikely because its members do not exhibit the derived characteristics of the lacrimal as seen in †T. pickfordi. Because Lake Tanganyika is located in the western branch of the East African Rift System, †T. pickfordi from the eastern branch supports the ‘melting-pot Tanganyika hypothesis,’ which posits that the cichlids of modern Lake Tanganyika are derived from riverine lineages that had already diversified prior to the lake formation.
Age Changes and Suicidal Activity in Iran Over the Past Decade: A Systematic Review and Meta-Analysis

This review study fills an important gap by aiming to determine the age changes in attempted and completed suicide in Iran during the past decade. A systematic review of related articles in international and Iranian databases from January 2008 to January 2020 was first conducted and relevant studies were extracted based on established criteria. Results showed that the mean age of suicide in Iran is 29.8 (range 27.7 – 31.8) years old for men and 27.4 (range 25.8 – 28.9) for women (P < 0.0001). The youngest and oldest populations of completed suicide belong to eastern and central regions of the country respectively. Findings imply the critical importance of increasing awareness through educational programs and public health campaigns to increase awareness and reduce suicidal behavior in Iran.
Histological and Immunohistochemical Observation of the Furcation Area Formation with the Subpulpal Lobus of Rat Molar

In the human molar, multirooted tooth formation occurs through the formation of dentin islands, termed subpulpal lobus, in the dental papilla. However, the mechanisms underlying subpulpal lobus formation currently remain unclear. Thus, using the rat molar, in which multirooted teeth formed through subpulpal lobus formation, similar to that in humans, we observed the process of subpulpal lobus formation over multirooted tooth formation histologically and immunohistologically, and discussed accessory root canal formation in the furcation area. The upper second molar (M2) was examined from rats 8 to 18 days after birth, stained with hematoxylin, and observed under a stereoscopic microscope. The maxilla including M2 was dissected out en bloc and decalcified, and paraffin-embedded sections were prepared following the standard method. Sections were subjected to hematoxylin-eosin double staining and immunohistochemical staining with anti-pan-keratin (PK), anti-heat shock protein 27 (HSP27), and anti-sonic hedgehog (Shh) antibodies. After the completion of tooth crown formation, a part of Hertwig’s epithelial root sheath (HERS) in the cervical region extended and formed an epithelial projection (EP) that was reactive with the anti-PK antibody. The EP induced the differentiation of dental papilla cells facing it into anti-Hsp27 antibody-reactive odontoblasts and formed the subpulpal lobus. EP and subpulpal lobus-forming odontoblasts reacted with the anti-Shh antibody, suggesting that cell differentiation in subpulpal lobus formation occurs through the epithelial-mesenchymal interaction. While forming subpulpal lobus, the EP extended without making contact with the opposing EP or HERS in the cervical region. The furcation area was formed by fusion between the dentin projection (DP) formed in the cervical region and subpulpal lobus and between subpulpal lobus. HERS in the cervical region and EP formed the furcation area without making contact with each other, suggesting that the accessory root canal is formed where DP and the subpulpal lobus do not fuse.
Different Roles of Stem/progenitor Cells in Vascular Remodelling.

SIGNIFICANCE Since the discovery of vascular stem cells, there has been significant progress in understanding the nature and functions of these cells. Due to their differentiation potential to repair endothelial cells and to participate in lesion formation during vascular remodelling, it is crucial to elucidate vascular stem cell behaviors and the mechanisms underlying this process, which may provide new possibilities for the development of clinical therapeutic application of stem cells. Recent Advances: Over the past decades, major progress has been made on vascular stem/progenitor cells in the field of cardiovascular research. Vascular stem cells are mostly quiescent in their niches, and can be activated in response to injury and participate in endothelial repair and smooth muscle cell accumulation to form neointima. Accumulating evidence has been shown recently, using genetic mouse models for cell lineage tracing, to specifically address the nature of vascular stem cells, and to monitor both cell migration and differentiation processes during physiological angiogenesis and in vascular diseases. CRITICAL ISSUES This article reviews and summarizes the current research progress of vascular stem cells in this field, and highlights future prospects for stem cell research in regenerative medicine. FUTURE DIRECTIONS Despite recent advances and achievements of stem cells in cardiovascular research, the nature and cell fate of vascular stem cells remain elusive. Further comprehensive studies using new techniques including genetic cell lineage tracing and single cell RNA sequencing are essential to fully illuminate the role of stem cells in vascular development and diseases.
Renewable Polysaccharides Micro/Nanostructures for Food and Cosmetic Applications

The worldwide diffusion of nanotechnologies into products nowadays has completely revolutionized human life, providing novel comfort and benefits. Their inclusion in food and cosmetic has a heavy impact over the market, allowing the development of higher value products with enhanced properties. Natural origin polymers and in particular polysaccharides represent a versatile platform of materials for the development of micro/nanostructured additives for food and cosmetic products due to their chemical versatility, biocompatibility, and abundance. Here, we review the current applications of polysaccharides-based micro/nanostructures, taking into consideration the precursors’ production, isolation, and extraction methods and highlighting the advantages, possible drawbacks, and market diffusion.
Exosomes derived from T regulatory cells relieve inflammatory bowel disease by transferring miR‐195a‐3p

Previous studies have demonstrated the therapeutic effects of regulatory T (Treg) cells on inflammatory bowel disease (IBD), but the mechanism is not well‐understood. Exosomes have been proposed as a novel mechanism underlying the action of Tregs. This study aimed to investigate the therapeutic effects of exosomes secreted by Treg cells (Treg‐Exo) on IBD and to explore the underlying mechanism. Treg‐Exo was isolated from BALB/c mouse spleen mononuclear cells and then injected into a murine model of IBD induced by dextran sodium sulfate (DSS) exposure. A co‐culture model of Treg‐Exo and colonic epithelial YAMC cells in the presence of TNF‐α was used to investigate the communication between Tregs and intestinal epithelial cells. in vitro results showed that Treg‐Exo could be transferred to YAMC cells where Treg‐Exo promoted cell proliferation and inhibited cell apoptosis. Animal experiments showed that Treg‐Exo administration alleviated the DSS‐induced IBD in mice. The therapeutic effects of Treg‐Exo both in vitro and in vivo were eliminated when miR‐195a‐3p expression was inhibited in Treg‐Exo. The pro‐apoptotic Caspase 12 was identified as a direct target of miR‐195a‐3p. In conclusion, Treg‐Exo alleviated the DSS‐induced IBD through transferring miR‐195a‐3p.
Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. Nuclear magnetic resonance (1H-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.
Effect of Different Concentration of Seaweed Saps on Quality, Green Fodder and Seed Yields of Berseem (Trifolium alexandrium)

A field experiment was conducted during rabi seasons 2012 and 2013 at research farm of Department of Agronomy Jawaharlal Nehru Krishi Vishwa-Vidyalaya, Jabalpur, Madhya Pradesh, India. The experiment was laid out in Randomized Block Design in three replications with ten treatments are as follows: RDF+2.5% K-sap, RDF+5% K sap, RDF+7.5% K sap, RDF+10% K sap, RDF+2.5% G sap, RDF+5% G sap, RDF+7.5% G sap, RDF+10% G sap, RDF+water spray, 50% RDF+6.25% K sap. The sowing date of Berseem varietyJB-5 were sown on 17th November, 2012 and 19th November of 2013. The highest GFY and DMY were recorded with the application of RDF with 10% G sap (613.45 and 83.24 q ha-1) followed by application of RDF+10% K sap (607.35 and 82.01 q ha-1), similarly the maximum seed yield and stover yield were recorded with the application of RDF with 10% G sap (4.72 and 62.36 q ha-1) followed by application of RDF+10% K sap (4.07 and 60.59 q ha-1), respectively due to presence of growth promoting hormones (Auxins, Cytokinins, Gibberellins), trace elements, vitamins, amino acids, antibiotics and micronutrients in these saps. The higher crude protein yield and crude fiber yield were observed under application of 10% G sap+RDF (11.67 and 15.10 q ha-1) followed by10% K sap+RDF (11.83 and 15.34 q ha-1). Art ic le History
Therapeutic Effect of Teriparatide for Osteoporotic Thoracolumbar Burst Fracture in Elderly Female Patients

Objective Teriparatide is known as an effective anabolic agent not only for severe osteoporosis but also for bone healing and union. We explored the possibility of teriparatide as an alternative treatment option for osteoporotic thoracolumbar (TL) burst fracture. Methods This retrospective study enrolled 35 female patients with mean age of 73.77±6.71 years (61–88) diagnosed as osteoporotic TL burst fracture with ≥4 of thoracolumbar injury classification and severity (TLICS) score and no neurological deficits. All patients were treated by teriparatide only (12 of group A), teriparatide plus vertebroplasty (12 of group B), or surgical fixation with fusion (11 of group C), and followed up for 12 months. Radiological outcomes were evaluated using radiological parameters including kyphotic angle (KA), segmental vertebral kyphotic angle (SVKA), compression ratio (CR), and vertebral body height (anterior [AH], middle [MH], posterior [PH]). Functional outcomes were evaluated using visual analog scale (VAS) and Macnab classification (MC). Results There were no statistical significant differences in age, bone mineral density (-3.36±0.73), and TLICS score (4.34±0.48) among the three groups (p>0.05). Teriparatide was administered during 8.63±2.32 months in group A and B. In 12-month radiological outcomes, there were significant restoration in SVKA, CR, AH, and MH of group B and KA, SVKA, CR, AH, and MH of group C compared to group A with no radiological changes (p<0.05). All groups showed similar significant improvements in 12-month functional outcomes, although group B and C showed a better 1-month VAS, 1-month MC, 3-month MC compared to group A (p<0.05). Conclusion Non-surgical treatment with teriparatide showed similar 12-month functional outcomes compared to surgical fixation with fusion. The additional vertebroplasty to teriparatide and surgical fixation with fusion were more helpful to improve short-term functional outcomes with structural restoration compared to teriparatide only.
High-Spatial-Resolution Three-dimensional Imaging of Human Spinal Cord and Column Anatomy with Postmortem X-ray Phase-Contrast Micro-CT.

Background Modern high-spatial-resolution radiologic methods enable increasingly detailed volumetric postmortem investigations of human neuroanatomy for diagnostic, research, and educational purposes. Purpose To evaluate the viability of postmortem x-ray phase-contrast micro-CT to provide tissue-conserving, high-spatial-resolution, three-dimensional neuroimaging of the human spinal cord and column by comparing quality of x-ray phase-contrast micro-CT images of nondissected Thiel-embalmed human spines with images of extracted formalin-fixed human spinal cords. Specific focus was placed on assessing the detection of micrometric spinal cord soft-tissue structure and vasculature. Materials and Methods In this study from August 2015 to August 2019, three Thiel-embalmed human spinal column samples, unilaterally perfused with an iodinated vascular contrast agent, and three extracted formalin-fixed spinal cord samples were imaged postmortem at a synchrotron radiation facility. Propagation-based x-ray phase-contrast micro-CT was used with monochromatic 60-keV x-rays and a detector with either 46-µm or 8-µm pixel sizes. A single-distance phase-retrieval algorithm was applied to the acquired CT projection images in advance of filtered back projection CT reconstruction. The influence on image quality of Thiel versus formalin embalming was examined, and images were qualitatively evaluated in terms of the value of their anatomic representations. Results The x-ray phase-contrast micro-CT of Thiel-embalmed samples resulted in soft-tissue contrast within the vertebral canal, despite evident nervous tissue deterioration after Thiel embalming. Gross spinal cord anatomy, spinal meninges, contrast agent-enhanced spinal vasculature, and spinal nerves were all well rendered alongside surrounding vertebral bone structure. The x-ray phase-contrast micro-CT of formalin-fixed boneless cords led to much higher gray versus white matter contrast and to microscale visualization of deep medullary vasculature and neuronal perikarya. Conclusion This work demonstrated the use of x-ray phase-contrast micro-CT for detailed volumetric anatomic visualization of embalmed human spines. The method provided three-dimensional display of bone, nervous tissue, and vasculature at microscale resolutions without exogenous contrast agents. © RSNA, 2020 Online supplemental material is available for this article.
The human CRY1 tail controls circadian timing by regulating its association with CLOCK:BMAL1

Significance Cryptochromes (CRYs) are structurally defined by an evolutionarily conserved PHR domain and divergent intrinsically disordered tails of variable length. Photosensory cryptochromes from plants and insects use reversible interactions between their PHR domain and disordered tails to control signal transduction. Although several studies have suggested that the tails of vertebrate cryptochromes influence circadian rhythms, nothing was known about the molecular mechanism. We used the DSPD CRY1Δ11 splice site variant to discover that the CRY1 tail interacts directly with its PHR domain and that the segment encoded by exon 11 regulates its affinity for CLOCK:BMAL1. Developing mechanistic insight into CRY1 regulation reveals common signaling mechanisms in cryptochromes and suggests strategies for treating prevalent circadian rhythm and sleep disorders. Circadian rhythms are generated by interlocked transcription–translation feedback loops that establish cell-autonomous biological timing of ∼24 h. Mutations in core clock genes that alter their stability or affinity for one another lead to changes in circadian period. The human CRY1Δ11 mutant lengthens circadian period to cause delayed sleep phase disorder (DSPD), characterized by a very late onset of sleep. CRY1 is a repressor that binds to the transcription factor CLOCK:BMAL1 to inhibit its activity and close the core feedback loop. We previously showed how the PHR (photolyase homology region) domain of CRY1 interacts with distinct sites on CLOCK and BMAL1 to sequester the transactivation domain from coactivators. However, the Δ11 variant alters an intrinsically disordered tail in CRY1 downstream of the PHR. We show here that the CRY1 tail, and in particular the region encoded by exon 11, modulates the affinity of the PHR domain for CLOCK:BMAL1. The PHR-binding epitope in exon 11 is necessary and sufficient to disrupt the interaction between CRY1 and the subunit CLOCK. Moreover, PHR–tail interactions are conserved in the paralog CRY2 and reduced when either CRY is bound to the circadian corepressor PERIOD2. Discovery of this autoregulatory role for the mammalian CRY1 tail and conservation of PHR–tail interactions in both mammalian cryptochromes highlights functional conservation with plant and insect cryptochromes, which also utilize PHR–tail interactions to reversibly control their activity.