Miracle-dz/UniFAR-FTUs huggingface dataset:
Minimally Invasive Screw Fixation Technique of Calcaneal Fractures

Orthopedic surgeons continue to seek new and better ways to successfully treat intra-articular calcaneus fractures. There is an increasing trend toward managing fractures through minimally invasive techniques. Such practices have been applied with increasing frequency to fractures of the calcaneus. Traditionally, limited-incision treatment has been reserved for Essex-Lopresti tongue-type fractures, but over the past decade practitioners have expanded the practice to joint depression variant fractures as well. The following discussion addresses considerations and techniques in managing calcaneus fractures by a small-incision approach.
The Importance of Accurate Diagnosis of ME/CFS in Children and Adolescents: A Commentary

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness that causes a range of debilitating symptoms. While most research has focused on adults, the illness also presents in children and adolescents. Many physicians find it difficult to diagnose the illness. In this commentary paper, we discuss a range of salient themes that have emerged from our ongoing research into the prevalence of ME/CFS in children and adolescents. We discuss reasons why pediatric prevalence estimates vary widely in the literature, from almost 0% to as high as 3%. We argue that there is considerable misdiagnosis of pediatric cases and over-inflation of estimates of pediatric ME/CFS. Many children and teenagers with general fatigue and other medical complaints may meet loose diagnostic criteria for ME/CFS. We make recommendations for improving epidemiological research and identifying pediatric ME/CFS in clinical practice.
High Dose Vitamin E Attenuates Diabetic Nephropathy via Alleviation of Autophagic Stress

It has been reported that autophagic stress, which is involved in many diseases, plays a key role in the development of diabetic nephropathy (DN). In this study, we investigated the effects of high dose vitamin E on renal tubular epithelial cells and autophagic stress-related mechanisms in diabetes condition. In diabetic rats, high dose vitamin E treatment significantly decreased the serum creatinine, urea nitrogen, urinary albumin and urinary protein, reduced the levels of LCN2, HAVCR1, LDH and 8-OHdG in urine, and attenuated the cellular apoptosis and interstitial fibrosis in renal cortex. In vitro, vitamin E could reduce the release of LCN2 and HAVCR1 and the protein levels of caspase 3 and TGF-β1, as well as improve the growth inhibition in cultured HK-2 cells after exposure to advanced glycation end products (AGEs). Also, LC3-II and SQSTM1-positive dots were significantly increased in the renal tubular epithelial cells of DN patients and diabetic rats, and in HK-2 cells after exposure to AGEs, which were markedly declined by vitamin E. In addition, we found that the autophagosome formation was not affected by AGEs, as assessed by the mRNA levels of LC3B, Beclin-1, and ATG7. However, AGEs blocked the lysosomal degradation of autophagosome, which was characterized by a decrease in the enzymatic activity of cathepsin B/cathepsin L and DQ-ovalbumin degradation in HK-2 cells, indicating that AGEs-induced accumulation of autophagic vacuoles was a sign of autophagic stress. Interestingly, vitamin E exerted a protective effect on lysosomes to reduce the autophagic stress. Taken together, we conclude that autophagic stress may play an important part in the progression of DN, and alleviation of autophagic stress though improvement of lysosomal function provides a promising novel approach for treating DN.
Nitration of Wheat Amylase Trypsin Inhibitors Increases Their Innate and Adaptive Immunostimulatory Potential in vitro

Amylase trypsin inhibitors (ATI) can be found in all gluten containing cereals and are, therefore, ingredient of basic foods like bread or pasta. In the gut ATI can mediate innate immunity via activation of the Toll-like receptor 4 (TLR4) on immune cells residing in the lamina propria, promoting intestinal, as well as extra-intestinal, inflammation. Inflammatory conditions can induce formation of peroxynitrite (ONOO−) and, thereby, endogenous protein nitration in the body. Moreover, air pollutants like ozone (O3) and nitrogen dioxide (NO2) can cause exogenous protein nitration in the environment. Both reaction pathways may lead to the nitration of ATI. To investigate if and how nitration modulates the immunostimulatory properties of ATI, they were chemically modified by three different methods simulating endogenous and exogenous protein nitration and tested in vitro. Here we show that ATI nitration was achieved by all three methods and lead to increased immune reactions. We found that ATI nitrated by tetranitromethane (TNM) or ONOO− lead to a significantly enhanced TLR4 activation. Furthermore, in human primary immune cells, TNM nitrated ATI induced a significantly higher T cell proliferation and release of Th1 and Th2 cytokines compared to unmodified ATI. Our findings implicate a causative chain between nitration, enhanced TLR4 stimulation, and adaptive immune responses, providing major implications for public health, as nitrated ATI may strongly promote inhalative wheat allergies (baker's asthma), non-celiac wheat sensitivity (NCWS), other allergies, and autoimmune diseases. This underlines the importance of future work analyzing the relationship between endo- and exogenous protein nitration, and the rise in incidence of ATI-related and other food hypersensitivities.
Moxibustion Modulates Sympathoexcitatory Cardiovascular Reflex Responses Through Paraventricular Nucleus

Electroacupuncture (EA) point specific (ST36-37) stimulation decreases cardiovascular reflex responses through supraspinal regions such as the hypothalamic paraventricular nucleus (PVN) while mechanical stimulation of acupoints decreases pressor responses through peripheral thermal transient receptor potential vanilloid type-1 (TRPV1). Moxibustion generating heat applied at acupoint in combination with antihypertensive drugs decreases elevated blood pressure. We hypothesized that moxibustion modulates sympathoexcitatory cardiovascular responses through the hypothalamic PVN and peripheral heat sensitive TRPV1 in the absence of antihypertensive drugs. Rats were anesthetized, ventilated, and heart rate and mean blood pressure were monitored. Gastric distention induced consistent pressor reflex responses every 10-min. Thirty-minutes of bilateral moxibustion at the acupoint ST36, overlying the deep peroneal nerves, reduced the gastric distention evoked elevation in blood pressure. Blood pressure reflex responses were not reduced by both EA and moxibustion at G39. The moxibustion inhibition but not EA inhibition of the cardiovascular responses was reversed with blockade of local heat sensitive TRPV1 at ST36. Accordingly, activation of thermal TRPV1 by moxibustion at an average of 44.2°C in contrast to 40°C reduced the pressor responses. Naloxone, an opioid receptor antagonist, microinjected into PVN inhibited transiently the effect of moxibustion. Thus, activation of peripheral heat sensitive TRPV1 mediated the moxibustion-inhibition, but not EA-inhibition, of sympathoexcitatory cardiovascular reflex responses through hypothalamic PVN opioid system.
TREC and KREC Levels as a Predictors of Lymphocyte Subpopulations Measured by Flow Cytometry

Primary immunodeficiency diseases (PID) is a heterogeneous group of disorders caused by genetic defects of the immune system, which manifests clinically as recurrent infections, autoimmune diseases, or malignancies. Early detection of other PID remains a challenge, particularly in older children due to milder and less specific symptoms, a low level of clinician PID awareness and poor provision of hospital laboratories with appropriate devices. T-cell recombination excision circles (TREC) and kappa-deleting element recombination circle (KREC) in a dried blood spot and in peripheral blood using real-time polymerase chain reaction (PCR) are used as a tool for severe combined immune deficiency but not in PID. They represent an attractive and cheap target for a more extensive use in clinical practice. This study aimed to assess TREC/KREC correspondence with lymphocyte subpopulations, measured by flow cytometry and evaluate correlations between TREC/KREC, lymphocyte subpopulations and immunoglobulins. We carried out analysis of data from children assessed by clinical immunologists at Speransky Children’s Hospital, Moscow, Russia with suspected immunodeficiencies between May 2013 and August 2016. Peripheral blood samples were sent for TREC/KREC, flow cytometry (CD3, CD4, CD8, and CD19), IgA, IgM, and IgG analysis. A total of 839 samples were analyzed for using TREC assay and flow cytometry and 931 KREC/flow cytometry. TREC demonstrated an AUC of 0.73 (95% CI 0.70–0.76) for CD3, 0.74 (95% CI 0.71–0.77) for CD4 and 0.67 (95% CI 0.63–0.70) for CD8, respectively, while KREC demonstrated an AUC of 0.72 (95% CI 0.69–0.76) for CD19. Moderate correlation was found between the levels of TREC and CD4 (r = 0.55, p < 0.01) and KREC with CD19 (r = 0.56, p < 0.01). In this study, promising prediction models were tested. We found that TREC and KREC are able to moderately detect abnormal levels of individual lymphocyte subpopulations. Future research should assess associations between TREC/KREC and other lymphocyte subpopulations and approach TREC/KREC use in PID diagnosis.
Fluid balance: sweat loss and fluid intake in humans

Hypohydration can impair the performance of exercise, and fluid balance is therefore of importance to athletes. This thesis aimed to investigate factors regarding fluid losses and gains, with a view to the performance of exercise. Chapter 3 investigated the effect of ingesting 600ml of hypotonic and hypertonic glucose solutions on blood, plasma and red cell volume in resting individuals. Ingestion of 6% and 12% hypertonic glucose solutions showed evidence of a transient decrease in blood and plasma volume possibly due to fluid movement into the intestinal lumen from the body. There was also a suggestion that ingestion of a 2% glucose solution increases blood and plasma volume in comparison to a 0% glucose solution. [Continues. ]
Increasing Sustained Participation in Free Mass Prostate Cancer Screening Clinics

Abstract : The overall objective of this study was to determine factors associated with sustaining regular participation in free prostate cancer screening clinics, particularly among African American men. Intervention strategies were designed and used at the community level by nurses in free screening clinics to improve screening sustainability. Strategies used in this study show that African American participation can be increased significantly. Men will respond to tailored messages. African American men who should be targeted for mass screening programs are those from lower educational attainment (less than high school and high school); African American men at age 40 and older who have never been screened; men who present for screening in their 40 s and 50 s but who decrease screening as they age; and African American men who present for an initial screening with no follow up screening in subsequent years. The challenge remains to sustain high participation in the free prostate cancer screening from one year to the next, and over several years. Churches can be a source of prostate cancer screening promotion once the church leaders identify men s health as a priority. The study sample contained 1,882 individuals primarily of African American and Caucasian ethnicity. Sustainability was at 40% for Blacks and 46% for Whites. Recruitment efforts in this study continued to be in the risk and age-related screening range that is supported by national health care organizations. We increased participation by African American men, and the majority of participants fell primarily in their 50 s and the next larger group in their 40 s. Consistency from one year to the next in scheduling free clinics and in developing marketing materials is important.
Automatic differentiation evaluated as a tool for rotorcraft design and optimization

This paper investigates the use of automatic differentiation (AD) as a means for generating sensitivity analyses in rotorcraft design and optimization. This technique transforms an existing computer program into a new program that performs sensitivity analysis in addition to the original analysis. The original FORTRAN program calculates a set of dependent (output) variables from a set of independent (input) variables, the new FORTRAN program calculates the partial derivatives of the dependent variables with respect to the independent variables. The AD technique is a systematic implementation of the chain rule of differentiation, this method produces derivatives to machine accuracy at a cost that is comparable with that of finite-differencing methods. For this study, an analysis code that consists of the Langley-developed hover analysis HOVT, the comprehensive rotor analysis CAMRAD/JA, and associated preprocessors is processed through the AD preprocessor ADIFOR 2.0. The resulting derivatives are compared with derivatives obtained from finite-differencing techniques. The derivatives obtained with ADIFOR 2.0 are exact within machine accuracy and do not depend on the selection of step-size, as are the derivatives obtained with finite-differencing techniques.
THE RENAL LESIONS OF ELECTROLYTE IMBALANCE

A dietary depletion of magnesium in rats leads to the production in the thin limb of Henle's loop of the nephrons of spherical microliths composed of a matrix of PAS-positive substances and calcium phosphate (3). These microliths grow by accretion to form intranephronic calculi. The classical pathological syndrome of clinical nephrolithiasis is thus reproduced within the nephron; to wit, the origin of the calculus at a certain level, local traumatic damage at the site of its origin, passage with the fluid flow down the urinary passages, lodgment of the calculus at some restricting point, obstruction of fluid flow and the usual consequent localized intrarenal "hydronephrotic" alterations of regressive atrophic cellular dysplasias within the nephron. To the classical description of the two forms of urinary lithiases occurring in the bladder and in the renal pelvis must therefore be added a third form, intranephronic calculosis. From the first origin of a microlith to its ultimate form as a calculus its organized structure is characterized by its matrix (PAS-positive materials) in which the periodic precipitation of crystalline mineral (Ca++, PO3 ---) occurs in a pattern simulating Liesegang rings.
Communications phase synchronization using the adaptive network fuzzy inference system (anfis)

The use of soft computing (SC) techniques in communications phase synchronization provides an alternative to analytical or hard computing methods. A review of current literature indicates that the application of soft computing to communications phase synchronization is in its infancy. In this work we derive new lower bounds on synchronizer performance, and demonstrate the use of a fuzzy logic-based approach in phase synchronization for a multiple-phase-shift-keying (M-PSK) communications system. Maximum Likelihood (ML) Estimation theory provides a basis for the most widely used phase estimation schemes. In this context, a review of ML statistical communication phase estimation theory and ad-hoc techniques for M-PSK modulation is presented first. New lower bounds on phase estimator performance are derived. These new Cramer-Rao Bounds (CRBs) provide the lower bound on which to judge the performance of any estimator for M-PSK modulation with a random phase model. Computational complexities and non-linear systems that result from statistical estimation theory for M-PSK systems are also addressed. Next the fundamentals of the principle constituents of soft computing, namely fuzzy logic and neural networks, are reviewed. The fundamentals of a hybrid soft computing technique known as Adaptive Neural Fuzzy Inference System (ANFIS) are discussed. Recent advances in communications that utilize soft computing approaches to phase synchronization are reviewed. Finally, the ANFIS approach is applied to phase synchronization for M-PSK. It is shown that the ANFIS approach overcomes many of the limitations of the Mamdani and statistical approaches. A comparison of statistical and ANFIS estimator performance is presented.
Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs

A retinal pigment epithelial patch derived from mutation-free pluripotent stem cells shows therapeutic effects in rats and pigs. A pipeline for retinal stem cell therapy Autologous induced pluripotent stem cell (iPSC)–derived retinal pigment epithelium (RPE) transplantation has been shown to improve visual function in animal models of age-related macular degeneration (AMD) and is currently being tested in human patients. However, oncogenic mutations might occur during the cell reprogramming process. Now, Sharma et al. used CD34+ peripheral blood cells from patients with AMD to generate oncogenic mutation-free iPSCs. These cells were used for the production of clinical-grade RPE cell patches. Transplantation of the RPE patches in rodent and pig models of retinal degeneration showed therapeutic effects. The authors suggest that the production process presented here might accelerate the development of safer iPSC-derived stem cell therapies. Considerable progress has been made in testing stem cell–derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.
Mapping the stochastic sequence of individual ligand-receptor binding events to cellular activation: T cells act on the rare events

Low-affinity ligands stimulate T cell responses when sequential antigen recognition events occur in nearby membrane regions. Linked events activate T cells How T cells discriminate between T cell receptor (TCR) ligands that do or do not stimulate cellular activation remains unclear. Lin et al mapped both the TCR input and NFAT activation response in single live T cells using simultaneous single-molecule and epifluorescence microscopy. By varying both the density and TCR affinity of the peptide-MHC input, they found that neither the total number nor the duration of input binding events fully explained T cell activation to all stimuli. Instead, correlation analysis indicated that T cells were activated by inputs coupled in space and time. These data clarify how T cells respond to low-affinity ligands, which may inform the development and use of cancer immunotherapies. T cell receptor (TCR) binding to agonist peptide major histocompatibility complex (pMHC) triggers signaling events that initiate T cell responses. This system is remarkably sensitive, requiring only a few binding events to successfully activate a cellular response. On average, activating pMHC ligands exhibit mean dwell times of at least a few seconds when bound to the TCR. However, a T cell accumulates pMHC-TCR interactions as a stochastic series of discrete, single-molecule binding events whose individual dwell times are broadly distributed. With activation occurring in response to only a handful of such binding events, individual cells are unlikely to experience the average binding time. Here, we mapped the ensemble of pMHC-TCR binding events in space and time while simultaneously monitoring cellular activation. Our findings revealed that T cell activation hinges on rare, long–dwell time binding events that are an order of magnitude longer than the average agonist pMHC-TCR dwell time. Furthermore, we observed that short pMHC-TCR binding events that were spatially correlated and temporally sequential led to cellular activation. These observations indicate that T cell antigen discrimination likely occurs by sensing the tail end of the pMHC-TCR binding dwell time distribution rather than its average properties.
Learning ambidextrous robot grasping policies

An ambidextrous grasping policy trained on synthetic datasets consistently clears bins of up to 25 novel objects with a physical robot. Universal picking (UP), or reliable robot grasping of a diverse range of novel objects from heaps, is a grand challenge for e-commerce order fulfillment, manufacturing, inspection, and home service robots. Optimizing the rate, reliability, and range of UP is difficult due to inherent uncertainty in sensing, control, and contact physics. This paper explores “ambidextrous” robot grasping, where two or more heterogeneous grippers are used. We present Dexterity Network (Dex-Net) 4.0, a substantial extension to previous versions of Dex-Net that learns policies for a given set of grippers by training on synthetic datasets using domain randomization with analytic models of physics and geometry. We train policies for a parallel-jaw and a vacuum-based suction cup gripper on 5 million synthetic depth images, grasps, and rewards generated from heaps of three-dimensional objects. On a physical robot with two grippers, the Dex-Net 4.0 policy consistently clears bins of up to 25 novel objects with reliability greater than 95% at a rate of more than 300 mean picks per hour.
Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

Serotherapy treats a transplant hurdle Cytomegalovirus (CMV) infection and reactivation are common and potentially fatal complications after bone marrow or hematopoietic stem cell transplantation (BMT). Martins et al. developed faithful preclinical murine models of CMV reactivation following BMT and found that humoral immunity can prevent this process (see the Perspective by Alegre). After BMT, antiviral antibodies that would have kept CMV at bay dwindle because host plasma cells are ablated and the donor B cell pool reconstitutes poorly. CMV reactivation was prevented by transferring antibody-containing immune serum. Such a therapeutic strategy would avoid some limitations of cellular therapies for BMT patients. Science, this issue p. 288; see also p. 232 Transfer of strain-specific antibodies after bone marrow transplant prevents cytomelagovirus reactivation in the recipient. Cytomegalovirus infection is a frequent and life-threatening complication that significantly limits positive transplantation outcomes. We developed preclinical mouse models of cytomegalovirus reactivation after transplantation and found that humoral immunity is essential for preventing viral recrudescence. Preexisting antiviral antibodies decreased after transplant in the presence of graft-versus-host disease and were not replaced, owing to poor reconstitution of donor B cells and elimination of recipient plasma cells. Viral reactivation was prevented by the transfer of immune serum, without a need to identify and target specific antigenic determinants. Notably, serotherapy afforded complete protection, provided that the serum was matched to the infecting viral strain. Thus, we define the mechanisms for cytomegalovirus reactivation after transplantation and identify a readily translatable strategy of exceptional potency, which avoids the constraints of cellular therapies.