Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation in individual reproductive performance amplified with population size in a long-lived carnivore.

Individual variation in reproductive ability is a key component of natural selection within populations, driving the evolution of life histories and population responses to changing environmental conditions. Evidence that population density affects individual-level fitness in wild populations is limited, particularly for long-lived animals which are difficult to observe on a biologically relevant scales. We tested for individual heterogeneity in reproductive performance in female grey seals (Halichoerus 16 grypus) using 35 years of mark-resighting data at Sable Island, Canada (43.93N 59.91W). We used Bayesian generalized linear mixed-effect models and multi-state open robust design mark-resight models to investigate whether population size negatively influences individual reproductive performance. We measured reproductive performance in two ways: reproductive frequency (the probability of returning to the island to breed) and annual provisioning performance (the probability of successfully weaning a pup given a female bred). Sighting histories of 1655 known-aged females with a total of 22961 pupping events were used for analysis. After accounting for effects of female age, parity, and random year effects, we found that both provisioning performance and reproductive frequency demonstrated a strong, positive correlation with population size. Among-individual variance in reproductive traits and responses to population size indicated considerable heterogeneity in overall reproductive performance. As population size grew, "robust" females increased their reproductive performance more than their more "frail" conspecifics in both reproductive traits, resulting in an amplification of differences among individuals. Consequently, simulations from posterior distributions revealed a large fitness consequence of heterogeneity in this population, with "frail" individuals having 47.1% fewer successful pups than more "robust" females (mean reproductive output ± SD: 9.12 ± 3.77 pups for frail individuals, 16.97 ± 2.94 for robust individuals). Repeatability of overall reproductive performance across environments indicates individual quality may be more influential to lifetime reproductive success than costs associated with reproductive investment. This quantification of relative fitness and its dynamics is crucial to understanding broad evolutionary processes in natural populations.
Analysis of the Machinability of Copper Alloy Ampcoloy by WEDM

The unconventional technology of wire electrical discharge machining is widely used in all areas of industry. For this reason, there is always an effort for efficient machining at the lowest possible cost. For this purpose, the following comprehensive study has been carried out to optimize the machining of the copper alloy Ampcoloy 35, which is particularly useful in plastic injection moulds. Within the study, a half-factor experiment of 25-1 with 10 axial points and seven central points of a total of 33 rounds was carried out, which was focused on the response monitoring of the input factors in the form of the machine parameters setup: gap voltage, pulse on time, pulse off time, discharge current, and wire speed. Based on the study of the response in the form of cutting speed and surface topography, their statistical models were created, while the optimal setting of machine parameters was determined to maximize the cutting speed and minimize the topography parameters. Further, a detailed cross-sectional analysis of surface and subsurface layer morphology was performed using electron microscopy including chemical composition analysis. In order to study microstructural changes in the material at the atomic level, a lamella was created, which was then studied using a transmission electron microscope.
SMAD4 protein is decreased in the dorsolateral prefrontal and anterior cingulate cortices in schizophrenia

Abstract Objectives Signal transduction through the mothers against decapentaplegic (SMAD) is a family of signal transduction factors that mediate signalling of the transforming growth factor B (TGFB)-superfamily of cell regulatory proteins. A recent transcriptomic analysis of post-mortem, cortical tissue from subjects with schizophrenia found decreased mRNA expression of SMAD2 and SMAD4 in the dorsolateral prefrontal cortex (DLPFC) associated with the disorder. To expand this initial finding, we sought to determine whether SMAD2 and SMAD4 protein were also altered in the cortex from subjects with schizophrenia. Methods Western blotting was used to measure SMAD2 and SMAD4 protein levels in DLPFC and anterior cingulate cortex (ACC) taken post-mortem from subjects with schizophrenia (n = 20) and matched control (n = 20) subjects. Results Compared to controls, levels of SMAD4 were 25% lower in the DLPFC and 38% lower in the ACC from subjects with schizophrenia. By contrast, SMAD2 levels were not altered in either DLPFC or ACC. Conclusions Our finding of lower SMAD4 protein in the cortex suggests there are likely to be abnormalities in cortical TGFB-superfamily signalling in schizophrenia.
Critical role for iron accumulation in the pathogenesis of fibrotic lung disease

Increased iron levels and dysregulated iron homeostasis, or both, occur in several lung diseases. Here, the effects of iron accumulation on the pathogenesis of pulmonary fibrosis and associated lung function decline was investigated using a combination of murine models of iron overload and bleomycin‐induced pulmonary fibrosis, primary human lung fibroblasts treated with iron, and histological samples from patients with or without idiopathic pulmonary fibrosis (IPF). Iron levels are significantly increased in iron overloaded transferrin receptor 2 (Tfr2) mutant mice and homeostatic iron regulator (Hfe) gene–deficient mice and this is associated with increases in airway fibrosis and reduced lung function. Furthermore, fibrosis and lung function decline are associated with pulmonary iron accumulation in bleomycin‐induced pulmonary fibrosis. In addition, we show that iron accumulation is increased in lung sections from patients with IPF and that human lung fibroblasts show greater proliferation and cytokine and extracellular matrix responses when exposed to increased iron levels. Significantly, we show that intranasal treatment with the iron chelator, deferoxamine (DFO), from the time when pulmonary iron levels accumulate, prevents airway fibrosis and decline in lung function in experimental pulmonary fibrosis. Pulmonary fibrosis is associated with an increase in Tfr1+ macrophages that display altered phenotype in disease, and DFO treatment modified the abundance of these cells. These experimental and clinical data demonstrate that increased accumulation of pulmonary iron plays a key role in the pathogenesis of pulmonary fibrosis and lung function decline. Furthermore, these data highlight the potential for the therapeutic targeting of increased pulmonary iron in the treatment of fibrotic lung diseases such as IPF. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Prehospital Mortality Due to Hemorrhagic Shock Remains High and Unchanged: A Summary of Current Civilian EMS Practices and New Military Changes

ABSTRACT Mortality secondary to trauma-related hemorrhagic shock has not improved for several decades. Underlying the stall in progress is the conundrum of effective prehospital interventions for hemorrhage control. As we know, neither pressing hard on the gas nor “stay and play” has changed mortality over the last 20 years. For this reason, when dealing with effective changes that will improve severe hemorrhage mortality outcomes, there is a need for the creation of a hybrid prehospital model. Improvements in mortality outcomes for patients with severe hemorrhage based on evidence for common civilian prehospital procedures such as in-field intubation and immediate fluid resuscitation with crystalloid solution are weak at best. The use of tourniquets, once considered too risky to use, however, has risen dramatically in large part due to success seen during their use in the military. Their use in the civilian setting shows promising results. Recently updated military Advanced Resuscitative Care guidelines propose the use of prehospital whole blood transfusion as well as in-field use of Zone 1 Resuscitative Endovascular Balloon Occlusion of the Aorta. Several case studies from Europe suggest these strategies are feasible for use in the civilian population, but could they be implemented in the US?
Effect of Exergaming on Muscle Strength, Pain, and Functionality of Shoulders in Cancer Patients.

Objective: To compare the strength of the middle deltoid muscle by means of dynamometry and the Shoulder Pain and Disability Index (SPADI) in participants in treatment for cancer after the practice of an exergaming protocol. Materials and Methods: We conducted a randomized controlled clinical trial. Thirty-eight voluntary participants were divided into two groups: cancer group (n = 19; age = 61.46 ± 8.79 years; body mass index [BMI] = 28.36 ± 4.94 kg/m3) and control group (n = 19; age = 57.62 ± 7.57 years; BMI = 28.06 ± 3.74 kg/m3), and they participated in the study. All participants performed an exergame protocol by using Xbox 360 Kinect® (Microsoft, Redmond) with the game Your Shape Fitness Evolved 2012 two to three times per week for 20 sessions. They were evaluated through the isometric dynamometer in the middle deltoid muscle and the SPADI at three moments: preintervention (EV1), after 10 sessions (EV2), and after 20 sessions (EV3). Results: The cancer group scored higher on both the disability index, in all three evaluations, and the pain index, in EV2 and EV3, when compared with the control group. There was a significant reduction in the disability score in EV2 and EV3 when compared with EV1 in the cancer group, whereas pain was lower in EV2 and EV3 when compared with EV1 in the control group. There were no significant interevaluation or intergroup differences in the maximal isometric voluntary contraction of the deltoid muscle of both upper limbs. Conclusion: At the end of the exergaming, protocol reduced the disability of the shoulder joint of the cancer group and decreased the differences between the groups for disability and pain scores, without changing isometric force.
Community Reintegration Following Holistic Milieu-Oriented Neurorehabilitation up to 30 Years Post-Discharge.

BACKGROUND The primary goal of neurorehabilitation for individuals with acquired brain injury (ABI) is successful community reintegration, which commonly focuses on home independence, productivity, and social engagement. Previous research has demonstrated that holistic treatment approaches have better long-term outcomes than other treatment approaches. Holistic approaches go beyond the fundamental components of neurorehabilitation and address metacognition and self-awareness, as well as interpersonal and functional skills. OBJECTIVES The present study aimed to examine community reintegration of individuals with ABI who completed holistic milieu-oriented neurorehabilitation at the Center for Transitional Neuro-Rehabilitation (CTN), Barrow Neurological Institute (BNI) at up to 30-years post-discharge. We evaluated (a) functional independence, (b) productivity and driving status, and (c) psychosocial profiles of the brain injury survivors. METHOD Participants included 107 individuals with ABI with heterogeneous etiologies who attended holistic milieu-oriented neurorehabilitation between 1986 and 2016. These participants completed the Mayo-Portland Adaptability Inventory-4 (MPAI-4) and a long-term outcome questionnaire (LOQ) specifically developed for this study. RESULTS The results demonstrate that 89% of participants were productive at up to 30 years post-discharge (73% engaged in competitive work and/or school) after excluding the retired participants. Almost all of the participants who were engaged in work and/or school reported using compensatory strategies on a long-term basis. Furthermore, only 14% out of 102 study participants were driving at the time of program admission; whereas 58% out of 96 were driving at the time of discharge; and impressively, 70% out of 107 participants were driving at the time of follow-up. Regression analyses revealed that older age at the time of injury, shorter duration between injury and treatment, and better functionality indicated by lower MPAI-4 Ability Index scores significantly predicted a return to driving status at the time of study participation. Psychosocial data from the LOQ revealed positive findings with respect to patients' marital status, living situation, income, and quality of social life. CONCLUSION The findings from this study suggest that functional gains made during holistic neurorehabilitation have enduring effects and that patients can benefit highly from holistic milieu therapy beyond the early post-acute phases of their recovery. Additionally, they provide evidence that there is potential to return to driving, years after treatment completion.Our holistic milieu treatment approach addressing metacognition, self-awareness, social and coping skills training, and actively transitioning to community settings, is thought to have contributed to the exceptional and long-lasting outcomes in this study.
Three is not enough

In the current issue of Transplant International, Assfalg et al. address the important question whether, in times of organ shortage, it is justified to perform a repeat kidney re-transplant (e.g. third or fourth transplant) (1). Compared to a first or second allograft, repeat kidney re-transplants were reported to show strongly impaired outcome (2). The authors analyzed 1,464 patients from 42 centers in the Eurotransplant area who received a third or fourth kidney transplant during 1996-2010.
The hTERT core promoter forms three parallel G-quadruplexes

Abstract The structure of the 68 nt sequence with G-quadruplex forming potential within the hTERT promoter is disputed. One model features a structure with three stacked parallel G-quadruplex units, while another features an unusual duplex hairpin structure adjoined to two stacked parallel and antiparallel quadruplexes. We report here the results of an integrated structural biology study designed to distinguish between these possibilities. As part of our study, we designed a sequence with an optimized hairpin structure and show that its biophysical and biochemical properties are inconsistent with the structure formed by the hTERT wild-type sequence. By using circular dichroism, thermal denaturation, nuclear magnetic resonance spectroscopy, analytical ultracentrifugation, small-angle X-ray scattering, molecular dynamics simulations and a DNase I cleavage assay we found that the wild type hTERT core promoter folds into a stacked, three-parallel G-quadruplex structure. The hairpin structure is inconsistent with all of our experimental data obtained with the wild-type sequence. All-atom models for both structures were constructed using molecular dynamics simulations. These models accurately predicted the experimental hydrodynamic properties measured for each structure. We found with certainty that the wild-type hTERT promoter sequence does not form a hairpin structure in solution, but rather folds into a compact stacked three-G-quadruplex conformation.
Dentin Bonding and SEM Analysis of a New Experimental Universal Adhesive System Containing a Dendrimer

Due to their polymerization characteristics, hyper-branched dendrimers have lately shown to be promising candidates for use in dental materials. In this study, a new dental adhesive system was prepared, using a dendrimer derived from 2-isocyanatoethyl methacrylate (G-IEMA), and its adhesive properties were investigated. The exposed dentin was treated with four universal adhesives (UAs): SBU (Scotchbond Universal™), FUT (Futurabond M+™), AE1 (experimental adhesive with Bis-GMA) and AE2 (experimental adhesive with G-IEMA), using Etch & Rinse (ER) or Self Etch (SE) protocols. Composite build-ups were prepared and stored for 24 h at 37 °C in distilled water. Composite/dentin beams were prepared with cross-sectional areas of 1 ± 0.3 mm2 and µTBS (Micro-tensile bond strength) test was performed at 0.5 mm/min. Failures modes were evaluated by stereomicroscopy, and bonding interfaces were observed by scanning electron microscopy (SEM). Statistical analysis of µTBS data was performed using General Linear (GLM) and Linear Mixed Models (LMM). The effect of adhesive type on µTBS was significant (p = 0.010), with AE1 presenting significantly higher µTBS than SBU (p = 0.019). No other differences between adhesives were observed. ER showed significantly better results than SE (p = 0.019), and no significant interactions between the adhesives and protocols were determined. Results obtained so far pinpoint the emergence of a new paradigm in the dental materials field, as G-IEMA can be used successfully as an alternative to Bis-GMA.
Developments in the treatment of Fabry disease

Enzyme replacement therapy (ERT) with recombinant α‐galactosidase A (r‐αGAL A) for the treatment of Fabry disease has been available for over 15 years. Long‐term treatment may slow down disease progression, but cardiac, renal, and cerebral complications still develop in most patients. In addition, lifelong intravenous treatment is burdensome. Therefore, several new treatment approaches have been explored over the past decade. Chaperone therapy (Migalastat; 1‐deoxygalactonojirimycin) is the only other currently approved therapy for Fabry disease. This oral small molecule aims to improve enzyme activity of mutated α‐galactosidase A and can only be used in patients with specific mutations. Treatments currently under evaluation in (pre)clinical trials are second generation enzyme replacement therapies (Pegunigalsidase‐alfa, Moss‐aGal), substrate reduction therapies (Venglustat and Lucerastat), mRNA‐ and gene‐based therapy. This review summarises the knowledge on currently available and potential future options for the treatment of Fabry disease.
Reelin signaling modulates GABAB receptor function in the neocortex

Reelin is a protein that is best known for its role in controlling neuronal layer formation in the developing cortex. Here, we studied its role for post‐natal cortical network function, which is poorly explored. To preclude early cortical migration defects caused by Reelin deficiency, we used a conditional Reelin knock‐out (RelncKO) mouse, and induced Reelin deficiency post‐natally. Induced Reelin deficiency caused hyperexcitability of the neocortical network in vitro and ex vivo. Blocking Reelin binding to its receptors ApoER2 and VLDLR resulted in a similar effect. Hyperexcitability in RelncKO organotypic slice cultures could be rescued by co‐culture with wild‐type organotypic slice cultures. Moreover, the GABAB receptor (GABABR) agonist baclofen failed to activate and the antagonist CGP35348 failed to block GABABRs in RelncKO mice. Immunolabeling of RelncKO cortical slices revealed a reduction in GABABR1 and GABABR2 surface expression at the plasma membrane and western blot of RelncKO cortical tissue revealed decreased phosphorylation of the GABABR2 subunit at serine 892 and increased phosphorylation at serine 783, reflecting receptor deactivation and proteolysis. These data show a role of Reelin in controlling early network activity, by modulating GABABR function.
Questionable Classification Accuracy Reported in “Designing a Sum of Squared Correlations Framework for Enhancing SSVEP-Based BCIs”

This commentary presents a replication study to verify the effectiveness of a sum of squared correlations (SSCOR)-based steady-state visual evoked potentials (SSVEPs) decoding method proposed by Kumar et al. We implemented the SSCOR-based method in accordance with their descriptions and estimated its classification accuracy using a benchmark SSVEP dataset with cross validation. Our results showed significantly lower classification accuracy compared with the ones reported in Kumar et al.’s study. We further investigated the sources of performance discrepancy by simulating data leakage between training and test datasets. The classification performance of the simulation was remarkably similar to those reported by Kumar et al. We, therefore, question the validity of evaluation and conclusions drawn in Kumar et al.’s study.
Comparative efficacy of teat sealants given prepartum for prevention of intramammary infections and clinical mastitis: a systematic review and network meta-analysis

Abstract A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.
Understanding the Performance of a Novel Direct Compression Excipient Comprising Roller Compacted Chitin

Chitin has been investigated in the context of finding new excipients suitable for direct compression, when subjected to roller compaction. Ball milling was concurrently carried out to compare effects from different energy or stress-inducing techniques. Samples of chitin powders (raw, processed, dried and humidified) were compared for variations in morphology, X-ray diffraction patterns, densities, FT-IR, flowability, compressibility and compactibility. Results confirmed the suitability of roller compaction to convert the fluffy powder of raw chitin to a bulky material with improved flow. X-ray powder diffraction studies showed that, in contrast to the high decrease in crystallinity upon ball milling, roller compaction manifested a slight deformation in the crystal lattice. Moreover, the new excipient showed high resistance to compression, due to the high compactibility of the granules formed. This was correlated to the significant extent of plastic deformation compared to the raw and ball milled forms of chitin. On the other hand, drying and humidification of raw and processed materials presented no added value to the compressibility and compactibility of the directly compressed excipient. Finally, compacted chitin showed direct compression similarity with microcrystalline cellulose when formulated with metronidazole (200 mg) without affecting the immediate drug release action of the drug.