Miracle-dz/UniFAR-FTUs huggingface dataset:
Host cell maturation modulates parasite invasion and sexual differentiation in Plasmodium berghei

Malaria remains a global health problem causing more than 400,000 deaths annually. Plasmodium parasites, the causative agents of malaria, replicate asexually in red blood cells (RBCs) of their vertebrate host, while a subset differentiates into sexual stages (gametocytes) for mosquito transmission. Parasite replication and gametocyte maturation in the erythropoietic niches of the bone marrow and spleen contribute to pathogenesis and drive transmission, but the mechanisms underlying this organ enrichment remain unknown. Here, we performed a comprehensive analysis of rodent P. berghei infection by flow cytometry and single-cell RNA sequencing. We identified CD71 as a host receptor for reticulocyte invasion and found that parasites metabolically adapt to the host cell environment. Transcriptional analysis and functional assays further revealed a nutrient-dependent tropism for gametocyte formation in reticulocytes. Together, we provide a thorough characterization of host-parasite interactions in erythropoietic niches and define host cell maturation state as the key driver of parasite adaptation.
Interactive Effects of Five Dental Implant Design Parameters on the Peak Strains at the Interfacial Bone: A Finite Element Study.

PURPOSE The aim of this study was to evaluate and compare the effect of changing five macrostructural design parameters of dental implants on the peak strains experienced by the interfacial bone. MATERIALS AND METHODS Five geometric variables, including three body-related (implant length, diameter, and taper) and two thread-related (thread depth and thread angle) parameters, were defined. The alveolar bone was modeled as a block with anisotropic and linearly elastic properties with 20-mm height and 12-mm buccolingual and mesiodistal dimensions. Oblique occlusal loads (100-N vertical and 20-N horizontal) were applied to the abutment surface. A total of 162 models with different designs were defined by implementation of a full-factorial design. The peak values of the compressive and tensile principal strains in the cortical and cancellous bones were calculated by finite element analysis (FEA). RESULTS Implant diameter and length had maximum and minimum effects on the peak compressive and tensile strains at the cortical interface, respectively. Implant diameter and thread depth had maximum and minimum effects on the maximum compressive strain at the cancellous interface, while thread angle and length had maximum and minimum significant effects on the maximum tensile strain at the cancellous interface. CONCLUSION The interaction of thread parameters and taper has the greatest effect on the peak compressive and tensile strains at the cancellous interface and also on the peak tensile strain at the cortical interface, while body-related parameters are more effective on the peak compressive strain at the cortical interface.
Use of WhatsApp messaging technology to strengthen obstetric referrals in the Greater Accra Region, Ghana: Findings from a feasibility study

In Ghana, the high-risk obstetric referral system is inadequate. Delay is common and patients often arrive to receiving hospitals in compromised states. An effective referral system should include an adequately resourced referral hospital, communication across sectors, accountability, transport, monitoring capability and policy support, which are currently lacking. A pilot program was undertaken to facilitate communication between hospital staffs. Additionally, data was collected to better understand and characterize obstetric referrals in Accra. Thirteen institutions were selected based on referral volume to implement the use of pre-referral treatment guidelines and WhatsApp as a mobile technology communication platform (Platform). Participants included healthcare workers from 8 health centers, 4 district hospitals, the Greater Accra Regional Hospital (GARH), administrators, doctors from other tertiary hospitals in Accra and medical consultants abroad. Facilities were provided smartphones and guidelines on using WhatsApp for advice on patient care or referral. Data were collected on WhatsApp communications among participants (March-August 2017). During this period, 618 cases were posted on the Platform and users increased from 69 to 81. The median response time was 17 min, a receiving hospital was identified 511 (82.7%) times and pre-referral treatment was initiated in 341 (55.2%). Subsequently, data collected on 597 referrals to GARH (September-November 2017) included 319 (53.4%) from Platform and 278 (46.6%) from non-Platform hospitals. Of these, 515 (86.3%) were urgent referrals; the median (interquartile range) referral to arrival time was 293 (111–1887) minutes without variation by facility grouping. Taxis were utilized for transportation in 80.2%; however, referral time shortened when patients arrived by ambulance and with a midwife. Only 23.5% of urgent referrals arrived within two hours. This project demonstrates that WhatsApp can be used as a communication tool for high-risk obstetric referrals and highlights the need to continue to improve urban referral processes due to identified delays which may contribute to poor outcomes.
Direct oral anticoagulation in atrial fibrillation and heart valve surgery—a meta-analysis and systematic review

Aims: Oral anticoagulation with direct oral anticoagulants (DOAC) could provide an alternative to vitamin K antagonists (VKA) for patients with atrial fibrillation (AF) undergoing bioprosthetic heart valve replacement or valve repair. Methods and results: The aim of this meta-analysis was to review the safety and efficacy of DOAC in patients with surgical implanted bioprosthetic heart valves or valve repairs and AF including data from six clinical trials with a total of 1,857 patients. The efficacy and safety data of DOAC and VKA were pooled to perform random-effects meta-analyses using the Mantel–Haenszel method with pooled risk ratios (RR) and 95% confidence interval (CI). A trial sequential analysis (TSA) was performed to assess statistical robustness. Death caused by cardiovascular cause or thromboembolic events were comparable (RR 0.67, 95% CI: 0.42–1.08; p = 0.10) as DOAC significantly reduced the risk for major bleeding (RR 0.55, 95% CI: 0.35–0.88; p = 0.01) and thromboembolic stroke or systemic embolism rates (RR 0.54, 95% CI: 0.32–0.90; p = 0.02). Rates for intracranial bleeding and hemorrhagic stroke (RR 0.27, 95% CI: 0.07–0.99; p = 0.05) show a trend toward fewer events in the DOAC group. Outcomes for major or minor bleeding events and all-cause mortality were comparable for DOAC and VKA. Conclusion: Cumulative data analysis reveals that DOAC may provide an effective and safe alternative to VKA in patients with AF after surgically implanted bioprosthetic heart valves or repair with AF. Within a relatively heterogeneous study population, this meta-analysis shows a risk reduction of major bleedings and thromboembolic stroke or systemic embolisms for DOAC.
In vitro and in vivo evaluation of brimonidine loaded silica nanoparticles-laden silicone contact lenses to manage glaucoma

Glaucoma is treated by frequent instillation of 0.2% w/v brimonidine tartrate eye drop solution, which showed poor ocular bioavailability of 1–3%. Medicated contact lenses can be used to improve the ocular drug bioavailability. However, drug loading in the contact lens matrix showed high burst release and changes the optophysical properties of the contact lens material. In this paper, a novel brimonidine loaded silica nanoparticles-laden silicone contact lenses (Bri-Si) were designed to achieve controlled drug delivery without altering the optophysical properties of the contact lens. Silica nanoparticles were prepared by polymerizing octadecyltrimethoxysilane (OTMS) molecules at the oil/water interface of microemulsion. Traditional soaking method (Bri-SM), direct brimonidine-loading method (Bri-DL) and microemulsion-laden contact lens (Bri-ME) were developed for comparison. The Bri-Si lens showed improved swelling, transmittance, oxygen permeability and lysozyme adherence compared to Bri-SM, Bri-DL and Bri-ME lenses. The Bri-DL lens showed high brimonidine leaching during extraction and sterilization steps, with low cumulative drug release. While, Bri-Si lens show controlled brimonidine release for 144 h. In a rabbit tear fluid model, the Bri-Si lens showed high brimonidine concentration for 96 h compared to Bri-ME lens and eye drop therapy. Based on histopathological studies of cornea, the Bri-Si lens was found to be safe for human applications. The data demonstrated the novel application of silica nanoparticles to control brimonidine release from the contact lens without altering the optophysical properties of the contact lens. Graphical Abstract
Disuse-induced skeletal muscle atrophy in disease and non-disease states in humans: mechanisms, prevention, and recovery strategies.

Decreased skeletal muscle contractile activity (disuse) or unloading leads to muscle mass loss, also known as muscle atrophy. The balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) is the primary determinant of skeletal muscle mass. A reduced mechanical load on skeletal muscle is one of the main external factors leading to muscle atrophy. However, endocrine and inflammatory factors can act synergistically in catabolic states, amplifying the atrophy process and accelerating its progression. Additionally, older individuals display aging-induced anabolic resistance, which can predispose this population to more pronounced effects when exposed to periods of reduced physical activity or mechanical unloading. Different cellular mechanisms contribute to the regulation of muscle protein balance during skeletal muscle atrophy. This review summarizes the effects of muscle disuse on muscle protein balance and the molecular mechanisms involved in muscle atrophy in the absence or presence of disease. Finally, a discussion of the current literature describing efficient strategies to prevent or improve the recovery from muscle atrophy is also presented.
Low Complexity Regions in Mammalian Proteins are Associated with Low Protein Abundance and High Transcript Abundance

Abstract Low Complexity Regions (LCRs) are present in a surprisingly large number of eukaryotic proteins. These highly repetitive and compositionally biased sequences are often structurally disordered, bind promiscuously, and evolve rapidly. Frequently studied in terms of evolutionary dynamics, little is known about how LCRs affect the expression of the proteins which contain them. It would be expected that rapidly evolving LCRs are unlikely to be tolerated in strongly conserved, highly abundant proteins, leading to lower overall abundance in proteins which contain LCRs. To test this hypothesis and examine the associations of protein abundance and transcript abundance with the presence of LCRs, we have integrated high-throughput data from across mammals. We have found that LCRs are indeed associated with reduced protein abundance, but are also associated with elevated transcript abundance. These associations are qualitatively consistent across 12 human tissues and nine mammalian species. The differential impacts of LCRs on abundance at the protein and transcript level are not explained by differences in either protein degradation rates or the inefficiency of translation for LCR containing proteins. We suggest that rapidly evolving LCRs are a source of selective pressure on the regulatory mechanisms which maintain steady-state protein abundance levels.
Electrotactile Perception Properties and Its Applications: A Review

With the increased demands of human-machine interaction, haptic feedback is becoming increasingly critical. However, the high cost, large size and low efficiency of current haptic systems severely hinder further development. As a portable and efficient technology, cutaneous electrotactile stimulation has shown promising potential for these issues. This paper presents a review on and insight into cutaneous electrotactile perception and its applications. Research results on perceptual properties and evaluation methods have been summarized and discussed to understand the effects of electrotactile stimulation on humans. Electrotactile applications are presented in categories to understand the methods and progress in various fields such as prostheses control, sensory substitution, sensory restoration and sensorimotor restoration. State of the art has demonstrated the superiority of electrotactile feedback, its efficiency and its flexibility. However, the complex factors and the limitations of evaluation methods made it challenging for precise electrotactile control. Groundbreaking innovation in electrotactile theory is expected to overcome challenges such as precise perception control, information capacity increasing, comprehension burden reducing and implementation costs.
3D Customized Biological Tibial Intramedullary Nail Fixation for the Treatment of Fracture after Massive Allograft Bone Transplantation of Tibial Osteosarcoma: A Case Report

Allograft bone fractures are critical complications in massive allograft bone transplantations. There are limited studies available on the application of 3D printing for massive allograft bone transplantation complications, and no related reports on the treatment of an allograft bone fracture with a complete biological intramedullary nail. A complex case of allograft bone fracture after massive bone transplantation for a right tibial osteosarcoma was treated with fixation of an individualized 3D printed biological tibial intramedullary nail. Prior to the operation, the intramedullary nail was designed and printed based on the results of computed tomography examination of the affected limb, and the surface of the intramedullary nail was treated with a hydroxyapatite coating. Intraoperatively, the intramedullary nail was implanted according to the preoperative 3D design plan. The intraoperative and postoperative examinations showed that the 3D printed intramedullary nail achieved good matching between the implant and the medullary cavity, and the biological coating integrated well with surrounding bone. The follow‐up results 44 months postoperatively showed that the patient was satisfied with the surgical results, where his ankle function met his daily needs, and the Musculoskeletal Tumor Society score was 24. 3D printing tibial intramedullary nail fixation can be successful in the treatment of allograft bone fractures and should be considered as a treatment of choice. In this case, the intramedullary nail matched the surrounding bone well, had good osseointegration, and the patient regained basic function.
Multistep Multiagent Reinforcement Learning for Optimal Energy Schedule Strategy of Charging Stations in Smart Grid

An efficient energy scheduling strategy of a charging station is crucial for stabilizing the electricity market and accommodating the charging demand of electric vehicles (EVs). Most of the existing studies on energy scheduling strategies fail to coordinate the process of energy purchasing and distribution and, thus, cannot balance the energy supply and demand. Besides, the existence of multiple charging stations in a complex scenario makes it difficult to develop a unified schedule strategy for different charging stations. In order to solve these problems, we propose a multiagent reinforcement learning (MARL) method to learn the optimal energy purchasing strategy and an online heuristic dispatching scheme to develop a energy distribution strategy in this article. Unlike the traditional scheduling methods, the two proposed strategies are coordinated with each other in both temporal and spatial dimensions to develop the unified energy scheduling strategy for charging stations. Specifically, the proposed MARL method combines the multiagent deep deterministic policy gradient (MADDPG) principles for learning purchasing strategy and a long short-term memory (LSTM) neural network for predicting the charging demand of EVs. Moreover, a multistep reward function is developed to accelerate the learning process. The proposed method is verified by comprehensive simulation experiments based on real data of the electricity market in Chicago. The experiment results show that the proposed method can achieve better performance than other state-of-the-art energy scheduling methods in the charging market in terms of the economic profits and users’ satisfaction ratio.
Anti-Mycobacterium abscessus Activity of Tuberculosis F-ATP Synthase Inhibitor GaMF1

New drug targets and molecules with bactericidal activity are needed against the respiratory mycobacterial pathogen Mycobacterium abscessus. Employing a lead repurposing strategy, the antituberculosis compound GaMF1 was tested against M. abscessus. ABSTRACT New drug targets and molecules with bactericidal activity are needed against the respiratory mycobacterial pathogen Mycobacterium abscessus. Employing a lead repurposing strategy, the antituberculosis compound GaMF1 was tested against M. abscessus. Whole-cell and ATP synthesis assays demonstrated that GaMF1 inhibits growth and kills M. abscessus by targeting the F-ATP synthase. GaMF1’s anti-M. abscessus activity increased in combination with clofazimine, rifabutin, or amikacin. The study expands the repertoire of anti-M. abscessus compounds targeting oxidative phosphorylation.
Hepcidin and Erythroferrone Complement the Athlete Biological Passport in the Detection of Autologous Blood Transfusion

ABSTRACT Purpose We investigated whether hepcidin and erythroferrone (ERFE) could complement the athlete biological passport (ABP) in indirectly detecting a 130-mL packed red blood cells (RBC) autologous blood transfusion. Endurance performance was evaluated. Methods Forty-eight healthy men (n = 24) and women (n = 24) participated. Baseline samples were collected weekly followed by randomization to a blood transfusion (BT, n = 24) or control group (CON, n = 24). Only the BT group donated 450 mL whole blood from which 130 mL red blood cell was reinfused 4 wk later. Blood samples were collected 3, 7, 14, 21, and 28 d after donation, and 3, 6, and 24 h and 2, 3, and 6 d after reinfusion. In the CON group samples were collected with the same frequency. Endurance performance was evaluated by a 650-kCal time trial (n = 13) before and 1 and 6 d after reinfusion. Results A time–treatment effect existed (P < 0.05) for hepcidin and ERFE. Hepcidin was increased (P < 0.01) ~110 and 89% 6 and 24 h after reinfusion. Using an individual approach (99% specificity, e.g., allowing 1:100 false-positive), sensitivities, i.e., true positives, of 30% and 61% was found for hepcidin and ERFE, respectively. For the ABP, the most sensitive marker was Off-hr score ([Hb] (g·L−1) − 60 × √RET%) (P < 0.05) with a maximal sensitivity of ~58% and ~9% after donation and reinfusion, respectively. Combining the findings for hepcidin, ERFE, and the ABP yielded a sensitivity across all time-points of 83% after reinfusion in BT. Endurance performance increased 24 h (+6.4%, P < 0.01) and 6 d after reinfusion (+5.8%, P < 0.01). Conclusions Hepcidin and ERFE may serve as biomarkers in an antidoping context after an ergogenic, small-volume blood transfusion.
Transplanted human cones incorporate into the retina and function in a murine cone degeneration model

Once human photoreceptors die, they do not regenerate, thus, photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation, and synaptic connectivity to the host will be critical in advancing this technology for use in clinical practice. Unlike the unstructured grafts of prior cell-suspension transplantations into end-stage degeneration models, we describe the extensive incorporation of induced pluripotent stem cell (iPSC) retinal organoid–derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extended throughout the graft, even forming a series of adherens junctions between mouse and human cells, reminiscent of an outer limiting membrane. Donor-host interaction appeared to promote polarization as well as the development of morphological features critical for light detection, namely the formation of inner and well-stacked outer segments oriented toward the retinal pigment epithelium. Putative synapse formation and graft function were evident at both structural and electrophysiological levels. Overall, these results show that human photoreceptors interacted readily with a partially degenerated retina. Moreover, incorporation into the host retina appeared to be beneficial to graft maturation, polarization, and function.
Physical activity and exercise recommendations for people receiving dialysis: A scoping review

Introduction Remaining physically active is important to patients undertaking dialysis, however, clinical recommendations regarding exercise type, timing, intensity, and safety precautions vary. The purpose of this scoping review was to analyse and summarise recommendations for physical activity and exercise for people undertaking dialysis and identify areas that require further research or clarification. Materials and methods A scoping review of literature from five bibliographic databases (Medline, Scopus, Web of Science, CINAHL, and SPORTDiscus) was conducted. Eligible articles included consensus guidelines, position statements, reviews, or clinical practice guidelines that included specific physical activity and exercise recommendations for people undertaking dialysis. Key search terms included "kidney disease" OR "kidney failure" OR "chronic kidney disease" OR "end stage kidney disease" AND guideline* OR consensus OR "position statement" OR prescription OR statement AND exercise OR "physical activity". Hand searching for relevant articles in all first twenty quartile 1 journals listed on SCImago under ‘medicine—nephrology’ and ‘physical therapy, sports therapy and rehabilitation’ using the terms ‘exercise and dialysis’ was undertaken. Finally, home pages of key societies and professional organisations in the field of sports medicine and nephrology were searched. Results The systematic search strategy identified 19 articles met the inclusion criteria. Two were specific to pediatric dialysis and three to peritoneal dialysis. Whilst many publications provided recommendations on aerobic exercise, progressive resistance training and flexibility, few provided explicit guidance. Recommendations for the intensity, duration and frequency of aerobic and resistance training varied. Discrepancies or gaps in guidance about precautions, contraindications, termination criteria, progression, and access site precautions were also apparent. Conclusion Future guidelines should include specific guidance regarding physical activity, safety precautions, and timing and intensity of exercise for individuals who undertake dialysis. Collaborative multidisciplinary guideline development and appropriate exercise counselling may lead to increased participation in physical activity and exercise and facilitate better patient outcomes.