Miracle-dz/UniFAR-FTUs huggingface dataset:
Heat But Not Mechanical Hypersensitivity Depends on Voltage-Gated CaV2.2 Calcium Channel Activity in Peripheral Axon Terminals Innervating Skin

Voltage-gated CaV2.2 calcium channels are expressed in nociceptors at presynaptic terminals, soma, and axons. CaV2.2 channel inhibitors applied to the spinal cord relieve pain in humans and rodents, especially during pathologic pain, but a biological function of nociceptor CaV2.2 channels in processing of nociception, outside presynaptic terminals in the spinal cord, is underappreciated. Here, we demonstrate that functional CaV2.2 channels in peripheral axons innervating skin are required for capsaicin-induced heat hypersensitivity in male and female mice. We show that CaV2.2 channels in TRPV1-nociceptor endings are activated by capsaicin-induced depolarization and contribute to increased intracellular calcium. Capsaicin induces hypersensitivity of both thermal nociceptors and mechanoreceptors, but only heat hypersensitivity depends on peripheral CaV2.2 channel activity, and especially a cell-type-specific CaV2.2 splice isoform. CaV2.2 channels at peripheral nerve endings might be important therapeutic targets to mitigate certain forms of chronic pain. SIGNIFICANCE STATEMENT It is generally assumed that nociceptor termini in the spinal cord dorsal horn are the functionally significant sites of CaV2.2 channel in control of transmitter release and the transmission of sensory information from the periphery to central sites. We show that peripheral CaV2.2 channels are essential for the classic heat hypersensitivity response to develop in skin following capsaicin exposure. This function of CaV2.2 is highly selective for heat, but not mechanical hypersensitivity induced by capsaicin exposure, and is not a property of closely related CaV2.1 channels. Our findings suggest that interrupting CaV2.2-dependent calcium entry in skin might reduce heat hypersensitivity that develops after noxious heat exposure and may limit the degree of heat hypersensitivity associated with certain other forms of pain.
Qualitative examination of the attitudes of healthcare workers in Turkey regarding COVID‐19 vaccines

Abstract Purpose The attitudes of healthcare workers toward COVID‐19 vaccines ensure that health services are able to run without interruption and potentially have a role in the messaging about vaccination that they convey to the public. Hence, healthcare workers’ attitudes ultimately have a significant role in controlling the pandemic. This study aimed to qualitatively investigate the attitudes of healthcare workers in Turkey in relation to COVID‐19 vaccines. Methods The study used the phenomenological approach. The sample consisted of 36 healthcare workers who were employed during the COVID‐19 pandemic. Data were collected online using focus group interviews. A total of four focus group interviews were conducted. Findings Following analysis of the data, the attitudes of healthcare workers in Turkey toward the COVID‐19 vaccine were divided into three themes: “influencing factors,” “priority group” and “trust. ” Conclusions Vaccination was found to create negative emotions among some of the healthcare workers. Their opinions about the COVID‐19 vaccines were affected by the negative emotions and burnout they experienced during the pandemic. In addition, they saw the vaccination process as impacted by contraindications and uncertainty about the duration of the protection, the balance of the benefits and harm of the vaccines, and by vaccine myths and prejudices about the country where the vaccine was developed. Healthcare professionals expressed the need for trust to be established in the whole vaccination process. They suggested that different vaccine options should be offered, that the appointment and process notification system for vaccination should be improved, that evidence‐based information about vaccines should be provided and that a safe environment should be created. Practice Implications Vaccine hesitancy can be addressed by careful attention to the application of vaccination programs, correct and effective use of social media, transparent, and precise management of political processes, and the provision of evidence‐based information about the vaccines.
NetControl4BioMed: a web-based platform for controllability analysis of protein–protein interaction networks

Abstract Motivation There is an increasing amount of data coming from genome-wide studies identifying disease-specific survivability-essential proteins and host factors critical to a cell becoming infected. Targeting such proteins has a strong potential for targeted, precision therapies. Typically however, too few of them are drug targetable. An alternative approach is to influence them through drug targetable proteins upstream of them. Structural target network controllability is a suitable solution to this problem. It aims to discover suitable source nodes (e.g. drug targetable proteins) in a directed interaction network that can control (through a suitable set of input functions) a desired set of targets. Results We introduce NetControl4BioMed, a free open-source web-based application that allows users to generate or upload directed protein–protein interaction networks and to perform target structural network controllability analyses on them. The analyses can be customized to focus the search on drug targetable source nodes, thus providing drug therapeutic suggestions. The application integrates protein data from HGNC, Ensemble, UniProt, NCBI and InnateDB, directed interaction data from InnateDB, Omnipath and SIGNOR, cell-line data from COLT and DepMap, and drug–target data from DrugBank. Availabilityand implementation The application and data are available online at https://netcontrol.combio. org/. The source code is available at https://github.com/Vilksar/NetControl4BioMed under an MIT license.
A MATHEMATICAL MODEL OF THE HUMAN CARDIAC SODIUM CHANNEL

Sodium ion (Na+) channels play an important role in excitable cells, as they are responsible for the initiation of action potentials. Understanding the electrical characteristics of sodium channels is essential in predicting their behavior under different physiological conditions. We investigated several Markov models for the human cardiac sodium channel (NaV1.5) to derive a minimal mathematical model that can describe the reported experimental data obtained using major voltage-clamp protocols. We obtained simulation results for current-voltage relationships, steady-state inactivation, the voltage dependence of normalized ion channel conductance; activation and deactivation, fast and slow inactivation and recovery from inactivation kinetics. Good agreement with the experimental data provides us with the mechanisms of the fast and slow inactivation of the human sodium channel and the coupling of its inactivation states to the closed and open states in the activation pathway. INDEX WORDS: Markov model, NaV1.5 channel, Inactivation, Recovery from inactivation, Voltage-clamp, Ion channel A MATHEMATICAL MODEL OF THE HUMAN CARDIAC SODIUM CHANNEL
The comparison of Kardia Mobile and Hartmann Veroval 2 in 1 in detecting first diagnosed atrial fibrillation

Background Atrial fibrillation (AF) is the leading cause of stroke. The European Society of Cardiology (ESC) advises opportunistic AF screening among patients aged ≥ 65 years. Considering this, the aim herein, was compare the feasibility of two different systems of smartphone-based electrocardiogram (ECG) recordings to identify AF among those without a previous arrhythmia history. Methods Prospective AF screening was conducted at six pharmacies using Kardia Mobile and Hartmann Veroval 2 in 1. A single-lead ECG was acquired by the placement of fingers on the pads. A cardiologist evaluated findings from both devices. Results Atrial fibrillation was identified in 3.60% and previously unknown AF was detected in 1.92% of the study participants. Sensitivity and specificity of the Kardia application in detecting AF were 66.7% (95% confidence interval [CI] 38.4–88.2%) and 98.5% (95% CI 96.7–99.5%), and for Veroval 10.0% (95% CI 0.23–44.5%) and 94.96% (95% CI 92.15–96.98%), accordingly. Inter-rater agreement was k = 0.088 (95% CI 1.59–16.1%). Conclusions Mobile devices can detect AF, but each finding must be verified by a professional. The Kardia application appeared to be more user-friendly than Veroval. Cardiovascular screening using mobile devices is feasible at pharmacies. Hence it might be considered for routine use.
In silico identification of natural antiviral compounds as a potential inhibitor of chikungunya virus non-structural protein 3 macrodomain

Abstract Chikungunya Virus (CHIKV) is having a major impact on humans with potentially life-threatening and debilitating arthritis. The lack of a specific antiviral drug against the CHIKV disease has created an alarming situation to identify or develop potent chemical molecules for its remedial measures. Antiviral therapies for viral diseases are generally expensive and have adverse side effects. Plant-based antiviral natural compounds are the most suitable and best alternative of current antiviral drugs because of less toxicity. In the present study, non-structural protein 3 macrodomain (nsP3MD) of the CHIKV that is essential for virus replication has been selected for anti CHIKV drug target. The compounds were identified using molecular docking, virtual screening and further evaluated by molecular dynamics (MD) simulation studies. The binding mechanism of each compound was analyzed considering the stability and energetic parameter. We have found six plant-based natural antiviral compounds Baicalin, Rutaecarpine, Amentoflavone, Apigetrin, Luteoloside, and Baloxavir as strong inhibitors of nsP3MD of CHIKV. ADMET prediction and target analysis of the selected compounds showed drug likeliness of these compounds. MD simulation studies indicated energetically favorable complex formation between nsP3MD and the selected antiviral compounds. Furthermore, the structural effects on these substitutions were analyzed using the principles of each trajectory, which validated the interaction studies. Our analysis suggests a very high probability of these compounds to inhibit nsP3MD of CHIKV and could be evaluated for Chikungunya fever drug development. Communicated by Ramaswamy H. Sarma
Streamwise and lateral maneuvers of a fish-inspired hydrofoil

Fish are highly maneuverable compared to human-made underwater vehicles. Maneuvers are inherently transient, so they are often studied via observations of fish and fish-like robots, where their dynamics cannot be recorded directly. To study maneuvers in isolation, we designed a new kind of wireless carriage whose air bushings allow a hydrofoil to maneuver semi-autonomously in a water channel. We show that modulating the hydrofoil's frequency, amplitude, pitch bias, and stroke speed ratio (pitching speed of left vs right stroke) produces streamwise and lateral maneuvers with mixed effectiveness. Modulating pitch bias, for example, produces quasi-steady lateral maneuvers with classic reverse von Kármán wakes, whereas modulating the stroke speed ratio produces sudden yaw torques and vortex pairs like those observed behind turning zebrafish. Our findings provide a new framework for considering in-plane maneuvers and streamwise/lateral trajectory corrections in fish and fish-inspired robots.
Impact of 18F-FET PET/MRI on Clinical Management of Brain Tumor Patients

Visual Abstract Multiparametric PET/MRI with the amino-acid analog O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) enables the simultaneous assessment of molecular, morphologic, and functional brain tumor characteristics. Although it is considered the most accurate noninvasive approach in brain tumors, its relevance for patient management is still under debate. Here, we report the diagnostic performance of 18F-FET PET/MRI and its impact on clinical management in a retrospective patient cohort. Methods: We retrospectively analyzed brain tumor patients who underwent 18F-FET PET/MRI between 2017 and 2018. 18F-FET PET/MRI examinations were indicated clinically because of equivocal standard imaging results or the clinical course. Histologic confirmation or clinical and standard imaging follow-up served as the reference standard. We evaluated 18F-FET PET/MRI accuracy in identifying malignancy in untreated suspected lesions (category, new diagnosis) and true progression during adjuvant treatment (category, detection of progression) in a clinical setting. Using multiple regression, we also estimated the contribution of single modalities to produce an optimal PET/MRI outcome. We assessed the recommended and applied therapies before and after 18F-FET PET/MRI and noted whether the treatment changed on the basis of the 18F-FET PET/MRI outcome. Results: We included 189 patients in the study. 18F-FET PET/MRI allowed the identification of malignancy at new diagnosis with an accuracy of 85% and identified true progression with an accuracy of 93%. Contrast enhancement, 18F-FET PET uptake, and tracer kinetics were the major contributors to an optimal PET/MRI outcome. In the previously equivocal patients, 18F-FET PET/MRI changed the clinical management in 33% of the untreated lesions and 53% of the cases of tumor progression. Conclusion: Our results suggest that 18F-FET PET/MRI helps clarify equivocal conditions and profoundly supports the clinical management of brain tumor patients. The optimal modality setting for 18F-FET PET/MRI and the clinical value of a simultaneous examination need further exploration. At a new diagnosis, multiparametric 18F-FET PET/MRI might help prevent unnecessary invasive procedures by ruling out malignancy; however, adding static 18F-FET PET to an already existing MRI examination seems to be of equal value. At detection of progression, multiparametric 18F-FET PET/MRI may increase therapy effectiveness by distinguishing between tumor progression and therapy-related imaging alterations.
Deceased Donor Liver Transplantation After Radioembolization for Hepatocellular Carcinoma and Portal Vein Tumoral Thrombosis: A Pilot Study

Hepatocellular carcinoma (HCC) with portal vein tumoral thrombosis (PVTT) represents a major concern especially in the field of deceased donor liver transplantation (DDLT). However, when receiving transarterial radioembolization (TARE), a considerable percentage of such patients are able to achieve a radiologic complete response with adequate survival rates. In this pilot prospective study, we evaluated the effect of TARE in downstaging HCC patients with PVTT to meet criteria for DDLT. Between May 2013 and November 2016, patients were evaluated to be enrolled into our “Superdownstaging” protocol. Patients received yttrium‐90 TARE and were enlisted for DDLT in case of complete and sustained (6 months) radiological response. Patients with tumor thrombus in the main trunk and/or in the contralateral portal vein branch were excluded. TARE was effective in downstaging and receiving DDLT in 5/17 patients (29.4%). The 5‐year overall survival was significantly higher in patients who underwent DDLT compared with those who were not transplanted (60.0% versus 0.0%, P = 0.03). Three out of 5 patients developed recurrence within 1 year after LT. The current series showed a clear survival gain in those patients who were able to receive DDLT after TARE but careful selection for DDLT is however advised.
Relationship Between Symptom Distress and Fatigue Characteristics in Patients with Gastric Cancer During 1 Month after Gastrectomy

This study’s purpose was to describe changes in symptom distress and fatigue characteristics identifying which symptoms significantly impacted fatigue characteristics of patients with Gastric Cancer (GC) within 1 month after gastrectomy. A prospective longitudinal study was conducted. Patients with GC who were scheduled for gastrectomy were recruited from surgical outpatient clinics and surgery wards in northern Taiwan. Data were collected using a set of questionnaires before (T0) and 7 (T1) and 28 days (T2) after gastrectomy. Over all, 86 patients experienced mild levels of fatigue and symptom distress. The changes in worst fatigue and fatigue interference were greatest at T1. Anxiety had a significant negative effect on both worst fatigue and fatigue interference. Dry mouth, pain, and body image had significant deleterious effects on worst fatigue. The co-occurring symptoms affecting fatigue for patients with GC in the acute phase after gastrectomy should be actively assessed to ensure optimal fatigue management.
Recent trends in impurity profiling and forced degradation of antihypertensive drugs

ABSTRACT This review describes the recent trends in analytical perspectives of impurity profiling and forced degradation of pharmaceutical drug and drug products used for the treatment of hypertension. Hypertension classes include diuretics, angiotensin receptor blocker, β adrenergic blocker, calcium channel blocker. Description based on use of various chromatographic methods, stationary phase, column, detectors are mentioned. Recent advancement in the field of impurity and stability study are focused on drugs belonging to these categories. GRAPHICAL ABSTRACT
Hematopoietic Stem Cells in Wound Healing Response

Significance: Emerging evidence has shown a link between the status of hematopoietic stem cells (HSCs) and wound healing responses. Thus, better understanding HSCs will contribute to further advances in wound healing research. Recent Advances: Myeloid cells such as neutrophils and monocyte-derived macrophages are critical players in the process of wound healing. HSCs actively respond to wound injury and other tissue insults, including infection and produce the effector myeloid cells, and a failing of the HSC response can result in impaired wound healing. Technological advances such as transcriptome at single-cell resolution, epigenetics, three-dimensional imaging, transgenic animals, and animal models, have provided novel concepts of myeloid generation (myelopoiesis) from HSCs, and have revealed cell-intrinsic and -extrinsic mechanisms that can impact HSC functions in the context of health conditions. Critical Issues: The newer concepts include—the programmed cellular fate at a differentiation stage that is used to be considered as the multilineage, the signaling pathways that can activate HSCs directly and indirectly, the mechanisms that can deteriorate HSCs, the roles and remodeling of the surrounding environment for HSCs and their progenitors (the niche). Future Directions: The researches on HSCs, which produce blood cells, should contribute to the development of blood biomarkers predicting a risk of chronic wounds, which may transform clinical practice of wound care with precision medicine for patients at high risk of poor healing.
Chronic Kidney Disease Testing Among At-Risk Adults in the U.S. Remains Low: Real-World Evidence From a National Laboratory Database

OBJECTIVE An estimated 37 million Americans have chronic kidney disease (CKD). Nearly 90% do not know about their condition because of low awareness about the importance of CKD testing and diagnosis among practitioners and people at risk for CKD. This study uses data from a national clinical laboratory to identify guideline-recommended CKD testing rates across the U.S. RESEARCH DESIGN AND METHODS Patients with Laboratory Corporation of America Holdings (Labcorp) testing between 2013 and 2019 were defined as at risk for CKD if they had any testing ordered with diagnosis codes for diabetes and/or hypertension. Guideline-concordant CKD assessment was defined by estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR) testing within the study year. RESULTS We identified 28,295,982 at-risk patients (mean age 60.6 ± 14.8 years; 53.6% women): 16.2% had diabetes, 63.8% had hypertension, and 20.1% had both comorbidities. Of these, 80.3% did not receive guideline-concordant assessment during the study period. Furthermore, only 21.0% had uACR testing versus 89.6% with eGFR. CKD assessment occurred at least once in 28.7% of patients with diabetes, 10.5% of patients with hypertension, and 41.4% of patients with both conditions. In a state-by-state comparison, annual testing rates ranged from 5 to 30%. The nationwide rate increased modestly each year between 2013 and 2018 (from 10.7% to 15.2%). CONCLUSIONS Despite guideline recommendations, testing for CKD with uACR and eGFR in U.S. adults with diabetes and hypertension is low in routine clinical care. These data highlight the need for strategies to improve routine CKD assessment nationwide.
RdRp or RT, That is the Question

Abstract The RNA-dependent RNA polymerase (RdRp) of all known double-stranded RNA viruses is located within the viral particle and is responsible for the transcription and replication of the viral genome. Through an RT-PCR assay, we determined that purified virions, in vitro translated RdRp proteins, and purified recombinant RdRp proteins of partitiviruses also have reverse transcriptase (RT) function. We show that partitivirus RdRps 1) synthesized DNA from homologous and heterologous dsRNA templates; 2) are active using both ssRNA and dsRNA templates; and 3) are active at lower temperatures compared to an optimal reaction temperature of commercial RT enzymes. This finding poses an intriguing question: why do partitiviruses, with dsRNA genomes, have a polymerase with RT functions? In comparison, 3Dpol, the RdRp of poliovirus, did not show any RT activity. Our findings lead us to propose a new evolutionary model for RNA viruses where the RdRp of dsRNA viruses could be the ancestor of RdRps.
Living well with dementia: The role volunteer-based social recreational programs in promoting social connectedness of people with dementia and their caregivers

Abstract Objectives: This evaluation study was designed to examine the factors that contribute the promotion of social connectedness among people with dementia and their caregivers through social recreational programs; develop an understanding of volunteer’s impact on program success; and identify the barriers and facilitators to improve the volunteer-based programs to promote social connectedness. Method: A qualitative descriptive research design was used to explore the study participants’ lived experiences of social recreational programs from Alzheimer’s Society of Durham Region (ASDR) in Ontario, Canada. A final sample of 31 participants was recruited including people with dementia, informal caregivers, and community volunteers. Qualitative data was collected through face-to-face semi-structured interviews. Emerging themes were derived from the qualitative descriptive data using thematic analysis. Results: The qualitative interviews highlighted the impact of social recreational programs on people with dementia, caregivers and volunteers in the promotion of social connectedness, as well as the examination of barriers and facilitators to identify opportunities for the future improvement of ASDR programs that would benefit the dementia populations. The study findings revealed that the project ‘Living Well with Dementia’ has been able to successfully foster social connectedness through its volunteer-led social recreational programs by promoting the physical and mental well-being of people with dementia and their caregivers. Conclusion: Our study findings underscored the critical roles of volunteers who contributed to the success of community-based programs. Future research is needed to identify the opportunities to address current gaps in services and to strengthen the social recreational programs using evidence-based practices and client-centered approaches. Supplemental data for this article can be accessed online at http://doi.org/10.1080/13607863.2021. 1950614.