Miracle-dz/UniFAR-FTUs huggingface dataset:
Deletion of VDAC1 Hinders Recovery of Mitochondrial and Renal Functions After Acute Kidney Injury

Voltage-dependent anion channels (VDACs) constitute major transporters mediating bidirectional movement of solutes between cytoplasm and mitochondria. We aimed to determine if VDAC1 plays a role in recovery of mitochondrial and kidney functions after ischemia-induced acute kidney injury (AKI). Kidney function decreased after ischemia and recovered in wild-type (WT), but not in VDAC1-deficient mice. Mitochondrial maximum respiration, activities of respiratory complexes and FoF1-ATPase, and ATP content in renal cortex decreased after ischemia and recovered in WT mice. VDAC1 deletion reduced respiration and ATP content in non-injured kidneys. Further, VDAC1 deletion blocked return of activities of respiratory complexes and FoF1-ATPase, and recovery of respiration and ATP content after ischemia. Deletion of VDAC1 exacerbated ischemia-induced mitochondrial fission, but did not aggravate morphological damage to proximal tubules after ischemia. However, VDAC1 deficiency impaired recovery of kidney morphology and increased renal interstitial collagen accumulation. Thus, our data show a novel role for VDAC1 in regulating renal mitochondrial dynamics and recovery of mitochondrial function and ATP levels after AKI. We conclude that the presence of VDAC1 (1) stimulates capacity of renal mitochondria for respiration and ATP production, (2) reduces mitochondrial fission, (3) promotes recovery of mitochondrial function and dynamics, renal morphology, and kidney functions, and (4) increases survival after AKI.
Increased Myocardial Oxygen Consumption Precedes Contractile Dysfunction in Hypertrophic Cardiomyopathy Caused by Pathogenic TNNT2 Gene Variants

Background Hypertrophic cardiomyopathy is caused by pathogenic sarcomere gene variants. Individuals with a thin‐filament variant present with milder hypertrophy than carriers of thick‐filament variants, although prognosis is poorer. Herein, we defined if decreased energetic status of the heart is an early pathomechanism in TNNT2 (troponin T gene) variant carriers. Methods and Results Fourteen individuals with TNNT2 variants (genotype positive), without left ventricular hypertrophy (G+/LVH−; n=6) and with LVH (G+/LVH+; n=8) and 14 healthy controls were included. All participants underwent cardiac magnetic resonance and [11C]‐acetate positron emission tomography imaging to assess LV myocardial oxygen consumption, contractile parameters and myocardial external efficiency. Cardiac efficiency was significantly reduced compared with controls in G+/LVH− and G+/LVH+. Lower myocardial external efficiency in G+/LVH− is explained by higher global and regional oxygen consumption compared with controls without changes in contractile parameters. Reduced myocardial external efficiency in G+/LVH+ is explained by the increase in LV mass and higher oxygen consumption. Septal oxygen consumption was significantly lower in G+/LVH+ compared with G+/LVH−. Although LV ejection fraction was higher in G+/LVH+, both systolic and diastolic strain parameters were lower compared with controls, which was most evident in the hypertrophied septal wall. Conclusions Using cardiac magnetic resonance and [11C]‐acetate positron emission tomography imaging, we show that G+/LVH− have an initial increase in oxygen consumption preceding contractile dysfunction and cardiac hypertrophy, followed by a decline in oxygen consumption in G+/LVH+. This suggests that high oxygen consumption and reduced myocardial external efficiency characterize the early gene variant–mediated disease mechanisms that may be used for early diagnosis and development of preventive treatments.
Newly diagnosed multiple myeloma: current treatment strategies, emerging therapeutic approaches and beyond

ABSTRACT Introduction As we have just stepped into a new decade of hopes, the mountain of knowledge learned from multiple myeloma (MM) remains unmatched among cancers. In the last decade alone, this rapid-sequence learning curve has led to regulatory approvals of eight drugs with mechanisms of actions representing five different areas of cell biology some of which made to the frontline setting, sparking debates about how to best sequence them in the treatment continuum of induction, consolidation, and maintenance and gained momentum with the realization of the implications of an effective upfront therapeutic approach with potential impact on survival. Areas covered This review was written with an intent to introduce the reader to the current treatment approach of a newly diagnosed myeloma patient and acquaint with promising targets and mechanistic strategies. Medline and clinicaltrials.gov databases (2000–2020) and relevant meetings (ASH, ASCO, EHA, ESMO, IMW) reports were queried and guidelines (IMWG) were reviewed to distill to expert opinion in an inundating field. Expert opinion Future holds promise with new targets on the horizon. It is likely that the new age of myeloma will belong to quadruplets with the addition of acellular or cellular biologics to first-generation novel agents, leading to new paradigms.
PDMeter: A Wrist Wearable Device for an at-Home Assessment of the Parkinson’s Disease Rigidity

This work focuses on the design and the validation of a wearable mechatronic device for an at-home assessment of wrist stiffness in patients affected by Parkinson’s Disease (PD). The device includes one actuated joint and four passive revolute joints with a high overall intrinsic backdriveability. In order to allow the user to freely move the wrist during activities of daily living, we implemented a transparent controller on the basis of the interaction force sensed by the embedded load cell. Conversely, in order to provide perturbations for estimating the wrist flexion-extension rigidity, we implemented a torque controller. Firstly, we report a pilot study that aimed at characterizing the device in terms of range of motion (ROM) allowed, transparency perceived and torque-tracking capability. Then, we present a case study in which we tested our device with seven PD patients in both drug-OFF and drug-ON conditions and we compared the measured stiffness with the one measured in fourteen healthy controls and with the outcome of the most used clinical scale (MDS-UPDRS). The device allowed to successfully estimate the stiffness as different depending on the movement direction. Indeed, extension stiffness was higher than the flexion one, accordingly to the literature. Moreover, the device allowed to discriminate both Healthy subjects from PD subjects, and PD subjects in OFF condition from PD subjects in ON condition. In conclusion, we demonstrate the feasibility of the device in measuring wrist rigidity, thus enabling the possibility to implement an at-home assessment of the PD rigidity.
Alphaherpesvirus gB Homologs Are Targeted to Extracellular Vesicles, but They Differentially Affect MHC Class II Molecules

Herpesvirus envelope glycoprotein B (gB) is one of the best-documented extracellular vesicle (EVs)-incorporated viral proteins. Regarding the sequence and structure conservation between gB homologs, we asked whether bovine herpesvirus-1 (BoHV-1) and pseudorabies virus (PRV)-encoded gB share the property of herpes simplex-1 (HSV-1) gB to be trafficked to EVs and affect major histocompatibility complex (MHC) class II. Our data highlight some conserved and differential features of the three gBs. We demonstrate that mature, fully processed BoHV-1 and PRV gBs localize to EVs isolated from constructed stable cell lines and EVs-enriched fractions from virus-infected cells. gB also shares the ability to co-localize with CD63 and MHC II in late endosomes. However, we report here a differential effect of the HSV-1, BoHV-1, and PRV glycoprotein on the surface MHC II levels, and MHC II loading to EVs in stable cell lines, which may result from their adverse ability to bind HLA-DR, with PRV gB being the most divergent. BoHV-1 and HSV-1 gB could retard HLA-DR exports to the plasma membrane. Our results confirm that the differential effect of gB on MHC II may require various mechanisms, either dependent on its complex formation or on inducing general alterations to the vesicular transport. EVs from virus-infected cells also contained other viral glycoproteins, like gD or gE, and they were enriched in MHC II. As shown for BoHV-1 gB- or BoHV-1-infected cell-derived vesicles, those EVs could bind anti-virus antibodies in ELISA, which supports the immunoregulatory potential of alphaherpesvirus gB.
Description of a Digital Work-Flow for CBCT-Guided Construction of Micro-Implant Supported Maxillary Skeletal Expander

The introduction of miniscrew-assisted rapid palatal expansion (MARPE) has widened the boundaries of orthodontic skeletal correction of maxillary transversal deficiency to late adolescence and adult patients. In this respect, Maxillary Skeletal Expander (MSE) is a particular device characterized by the engagement of four miniscrews in the palatal and nasal cortical bone layers. Thus, the availability of sufficient supporting bone and the perforation of both cortical laminas (bi-corticalism) are two mandatory parameters for mini-screw stability, especially when orthopedic forces are used. Virtual planning and construction of MSE based on cone-beam computed tomography (CBCT)-derived stereolithography (.stl) files have been recently described in the literature. In this manuscript we described: (a) a user-friendly digital workflow which can provide a predictable placement of maxillary skeletal expander (MSE) appliance according to the patient’s anatomical characteristics, (b) the construction of a positional template of the MSE that allows lab technician to construct the MSE appliance in a reliable and accurate position, according to the virtual project planned by the orthodontist on the patient CBCT scans. We also described a case report of an adult female patient affected by skeletal transversal maxillary deficiency treated with MSE appliance that was projected according to the described workflow.
Differences in the Response to DNA Double-Strand Breaks between Rod Photoreceptors of Rodents, Pigs, and Humans

Genome editing (GE) represents a powerful approach to fight inherited blinding diseases in which the underlying mutations cause the degeneration of the light sensing photoreceptor cells of the retina. Successful GE requires the efficient repair of DNA double-stranded breaks (DSBs) generated during the treatment. Rod photoreceptors of adult mice have a highly specialized chromatin organization, do not efficiently express a variety of DSB response genes and repair DSBs very inefficiently. The DSB repair efficiency in rods of other species including humans is unknown. Here, we used ionizing radiation to analyze the DSB response in rods of various nocturnal and diurnal species, including genetically modified mice, pigs, and humans. We show that the inefficient repair of DSBs in adult mouse rods does not result from their specialized chromatin organization. Instead, the DSB repair efficiency in rods correlates with the level of Kruppel-associated protein-1 (KAP1) expression and its ataxia-telangiectasia mutated (ATM)-dependent phosphorylation. Strikingly, we detected robust KAP1 expression and phosphorylation only in human rods but not in rods of other diurnal species including pigs. Hence, our study provides important information about the uniqueness of the DSB response in human rods which needs to be considered when choosing model systems for the development of GE strategies.
Social Human-Robot Interaction for Gait Rehabilitation

Robot-assisted therapy for gait rehabilitation of patients with neurological disorders usually combines a body weight support system with a treadmill system. Lokomat is one of the most used devices for gait rehabilitation. This device allows therapists to focus on the patient and the therapy. However, this therapy session is based on multi-tasking processes, which are often difficult for a therapist to manage. In this work, a Socially Assistive Robot (SAR) was integrated into a neurorehabilitation program as a collaborator agent to promote patient engagement and performance during the therapy. This short-term study presents the effects comparing the social robot condition and control condition with a group of four neurological patients using repeated measurement design. As a remarkable result, patients improved thoracic 18.44% and cervical 32.23% posture on average with SAR assistance. This study demonstrated the feasibility of the integration of a social robot as a complement of gait rehabilitation programs.
Preparation and Structural Characterization of Complex Oxide Eutectic Precursors from Polymer–Salt Xerogels Obtained by Microwave-Assisted Drying

Sol–gel synthesis is an acknowledged method for obtaining fine inorganic powders of a different nature. Implementation of water-soluble polymers as gel-forming media makes this technique even more readily available, especially in cases where conventional gel formation is suppressed. In polymer–salt solutions, polymers serve as scaffolds for salt constituents’ bulk crystallization. When dried, solid salt particles are deposited on the polymer surface or in polymer matrix pores, which leads to higher grain size uniformity. The present work discusses the effect of drying conditions on phase composition and structure characteristics of complex oxide eutectics in ternary systems, CaO–Al2O3–Y2O3 (CAY) and MgO–Al2O3–Y2O3 (MAY), obtained from polymer–salt compositions based on polyvinyl alcohol (PVA), Na-salt of carboxymethylcellulose (Na-CMC) or polyvinylpyrrolidone (PVP). Microwave-assisted drying proved to be more efficient compared to convective process; however such technique requires careful selection of gel-forming polymer.
ResearchCOVID‐19 Preparedness in Michigan Nursing Homes

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately high mortality among older adults, particularly those with comorbidities. Nursing homes (NHs) are particularly vulnerable to widespread transmission and poor outcomes. The objectives of this study were (1) to understand preparedness among Michigan NHs in the midst of an ongoing pandemic and (2) to compare with a 2007 survey on pandemic influenza preparedness in Michigan NHs.
A Durable Hybrid RAM Disk with a Rapid Resilience for Sustainable IoT Devices

Flash-based storage is considered to be a de facto storage module for sustainable Internet of things (IoT) platforms under a harsh environment due to its relatively fast speed and operational stability compared to disk storage. Although their performance is considerably faster than disk-based mechanical storage devices, the read and write latency still could not catch up with that of Random-access memory (RAM). Therefore, RAM could be used as storage devices or systems for time-critical IoT applications. Despite such advantages of RAM, a RAM-based storage system has limitations in its use for sustainable IoT devices due to its nature of volatile storage. As a remedy to this problem, this paper presents a durable hybrid RAM disk enhanced with a new read interface. The proposed durable hybrid RAM disk is designed for sustainable IoT devices that require not only high read/write performance but also data durability. It includes two performance improvement schemes: rapid resilience with a fast initialization and direct byte read (DBR). The rapid resilience with a fast initialization shortens the long booting time required to initialize the durable hybrid RAM disk. The new read interface, DBR, enables the durable hybrid RAM disk to bypass the disk cache, which is an overhead in RAM-based storages. DBR performs byte–range I/O, whereas direct I/O requires block-range I/O; therefore, it provides a more efficient interface than direct I/O. The presented schemes and device were implemented in the Linux kernel. Experimental evaluations were performed using various benchmarks at the block level till the file level. In workloads where reads and writes were mixed, the durable hybrid RAM disk showed 15 times better performance than that of Solid-state drive (SSD) itself.
Gait Characteristics under Imposed Challenge Speed Conditions in Patients with Parkinson’s Disease During Overground Walking

Evaluating gait stability at slower or faster speeds and self-preferred speeds based on continuous steps may assist in determining the severity of motor symptoms in Parkinson’s disease (PD) patients. This study aimed to investigate the gait ability at imposed speed conditions in PD patients during overground walking. Overall, 74 PD patients and 52 age-matched healthy controls were recruited. Levodopa was administered to patients in the PD group, and all participants completed imposed slower, preferred, and faster speed walking tests along a straight 15-m walkway wearing shoe-type inertial measurement units. Reliability of the slower and faster conditions between the estimated and measured speeds indicated excellent agreement for PD patients and controls. PD patients demonstrated higher gait asymmetry (GA) and coefficient of variance (CV) for stride length and stance phase than the controls at slower speeds and higher CVs for phases for single support, double support, and stance. CV of the double support phase could distinguish between PD patients and controls at faster speeds. The GA and CVs of stride length and phase-related variables were associated with motor symptoms in PD patients. Speed conditions should be considered during gait analysis. Gait variability could evaluate the severity of motor symptoms in PD patients.
Highly Efficient Symmetric Key Based Authentication and Key Agreement Protocol Using Keccak

Efficient authentication and key agreement protocols between two entities are required in many application areas. In particular, for client–server type of architectures, the client is mostly represented by a constrained device and thus highly efficient protocols are needed. We propose in this paper two protocols enabling the construction of a mutual authenticated key ensuring anonymity and unlinkability of the client and resisting the most well known attacks. The main difference between the two proposed protocols is in the storage requirements on the server side. The innovation of our protocols relies on the fact that, thanks to the usage of the sponge construction, available in the newly proposed SHA3 standard with underlying Keccak design, the computation cost can be reduced to only one hash operation on the client side in case of the protocol with storage and two hash operations for the protocol without storage and thus leads to a very efficient solution.
Detection of Atrial Fibrillation Using 1D Convolutional Neural Network

The automatic detection of atrial fibrillation (AF) is crucial for its association with the risk of embolic stroke. Most of the existing AF detection methods usually convert 1D time-series electrocardiogram (ECG) signal into 2D spectrogram to train a complex AF detection system, which results in heavy training computation and high implementation cost. This paper proposes an AF detection method based on an end-to-end 1D convolutional neural network (CNN) architecture to raise the detection accuracy and reduce network complexity. By investigating the impact of major components of a convolutional block on detection accuracy and using grid search to obtain optimal hyperparameters of the CNN, we develop a simple, yet effective 1D CNN. Since the dataset provided by PhysioNet Challenge 2017 contains ECG recordings with different lengths, we also propose a length normalization algorithm to generate equal-length records to meet the requirement of CNN. Experimental results and analysis indicate that our method of 1D CNN achieves an average F1 score of 78.2%, which has better detection accuracy with lower network complexity, as compared with the existing deep learning-based methods.
Coherent Integration Method Based on Radon-NUFFT for Moving Target Detection Using Frequency Agile Radar

This paper considers the coherent integration problem for moving target detection using frequency agile (FA) radar, involving range cell migration (RCM) and the nonuniform phase fluctuations among different pulses caused by range-agile frequency (R-AF) coupling and velocity-time-agile frequency (V-T-AF) coupling. After the analysis of the term corresponding to the phase fluctuation caused by V-T-AF coupling, the term can be regarded as related to an equivalent non-uniform slow time, and nonuniform fast Fourier transform (NUFFT) could be the solution. So a fast coherent integration method combining Radon Fourier transform (RFT) and NUFFT based on low-rank approximation, i.e., Radon-NUFFT, is proposed. In this method, the RCM is solved by Radon algorithm via target trajectory searching, the non-uniform phase fluctuation caused by R-AF coupling is compensated by constructing a compensation item corresponding to the range and agile frequency. In addition, the compensation of the non-uniform phase fluctuation caused by V-T-AF coupling is converted into a problem of spectral analysis of non-uniform sampling complex-valued signal, which is solved by the NUFFT based on low rank approximation. Compared with the existing methods, the proposed method can realize the coherent integration for FA radar accurately and quickly. The effectiveness of the proposed method is verified by simulation experiments.
AKT3 deficiency in M2 macrophages impairs cutaneous wound healing by disrupting tissue remodeling

AKT signaling and M2 macrophage-guided tissue repair are key factors in cutaneous wound healing. A delay in this process threatens human health worldwide. However, the role of AKT3 in delayed cutaneous wound healing is largely unknown. In this study, histological staining and transcriptomics demonstrated that prolonged tissue remodeling delayed wound healing. This delay was accompanied by defects in AKT3, collagen alpha-1(I) chain (COL1A1), and collagen alpha-1(XI) chain (COL11A1) expression and AKT signaling. The defect in AKT3 expression was M2 macrophage-specific, and decreased AKT3 protein levels were observed in CD68/CD206-positive macrophages from delayed wound tissue. Downregulation of AKT3 in M2 macrophages did not influence cell polarization but impaired collagen organization by inhibiting COL1A1 and COL11A1 expression in human skin fibroblasts (HSFs). Moreover, a co-culture model revealed that the downregulation of AKT3 in the human monocytic cell line (THP-1)-derived M2 macrophages impaired HSF proliferation and migration. Finally, cutaneous wound healing in AKT3-/- mice was much slower than that of AKT3+/+ mice, and F4/80 macrophages from the AKT3-/- mice had an impaired ability to promote wound healing. Thus, the downregulation of AKT3 in M2 macrophages prolonged tissue remodeling and delayed cutaneous wound healing.
Multiscale Modeling of Human Skin Oil-Induced Indoor Air Chemistry: Combining Kinetic Models and Molecular Dynamics.

We performed classical molecular dynamics simulations to quantify and understand the non-reactive, dermal uptake of volatile organic compounds formed during the ozonolysis of human skin oils. Our results include surface accommodation coefficients, partitioning constants, bulk diffusivities, and desorption lifetimes. These parameters were used to improve and to constrain the kinetic multilayer model of the surface and bulk chemistry of skin (KM-SUB-Skin). By comparing common outputs (bulk accommodation coefficients), we cross-validate the two approaches, and thus increase the level of trust in their predictions relevant to indoor air chemistry.