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Preimplantation genetic testing for aneuploidy (PGT-A) has become a useful approach for embryo selection following IVF and ICSI. However, the biopsy process associated with PGT-A is expensive, prone to errors in embryo ploidy determination, and potentially damaging, impacting competence and implantation potential. Therefore, a less invasive method of PGT-A would be desirable and more cost-effective. Noninvasive methods for PGT-A (ni-PGT-A) have been well-studied but present limitations in terms of cf-DNA origin and diagnostic accuracy. Minimally invasive pre-implantation genetic testing (mi-PGT-A) for frozen-thawed embryo transfer is a promising, less studied approach that utilizes a combination of spent culture media (SCM) and blastocoelic fluid (BF)-derived cell-free (CF)-DNA for genetic testing. This study aimed to optimize the effectiveness of mi-PGT-A for aneuploidy diagnosis by investigating the optimal temporal sequence for this protocol. SCM+BF was collected at either 48 or 72 h of culture after thawing day 3 preimplantation embryos. cf-DNA in the SCM+BF was amplified, analyzed by next-generation sequencing (NGS) and compared with results from the corresponding whole embryos (WEs) obtained from human embryos donated for research. Fifty-three (42 expanded blastocysts, 9 early blastocysts, and 2 morula) WE and SCM+BF samples were analyzed and compared. The overall concordance rate between SCM+BF and WE was 60%. Gender and ploidy concordance improved with extended culture time from 48 h (73% and 45%) to 72 h (100% and 64%), respectively. These results demonstrate that SCM+BF-derived cf-DNA can be successfully used for mi-PGT-A. Our findings indicate that longer embryo culture time prior to SCM+BF-derived cf-DNA analysis improves DNA detection rate and concordance with WEs and decreases the proportion of false positive results.

Objectives Early treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and improving patients’ quality of life. The PRAIRI study was a randomised, double-blind, placebo-controlled trial with the B-cell depleting agent rituximab (RTX), which resulted in a significant delay of arthritis development of up to 12 months in seropositive RA-risk individuals. Here, we report our findings on patient-reported outcomes (PROs) in this study population.Methods Seventy-eight RA-risk individuals were treated with one single dose of either placebo (PBO) or 1000 mg RTX plus 100 mg methylprednisolone (MP) and anti-histamines, regardless of treatment allocation, as co-medication. Data on quality of life were collected at baseline and 1, 4, 6, 12 and 24 months using established PRO questionnaires (visual analogue scale (VAS) pain, health assessment questionnaire disability index (HAQ-DI) score, EuroQol five dimension (EQ-5D) and both physical and mental component score of the 36-item short-form heath survey (SF-36)).Results No significant changes in quality of life over a 2 year follow-up were observed in at-risk individuals treated with RTX compared to PBO given the PRO scores at 24 months (mean difference±SEM: HAQ score=0.07±0.16; EQ-5D=−0.02±0.05; VAS pain=11.11±7.40). Furthermore, no significant effect of treatment on perceived arthritis severity at the time of clinically manifest disease (arthritis) was found.Conclusion One single dose of RTX plus MP administered to RA-risk individuals does not have a meaningful and measurable positive effect on PROs after 2 years of follow-up and/or perceived disease severity at the time of arthritis development.Trial registration number Trial registered at EU Clinical Trial Register, EudraCT Number: 2009-010955-29 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=Prevention+of+RA+by+B+cell+directed+therapy).

Abstatct: Introduction: Immune checkpoints are regulators of the immune system response that allow self-tolerance. Molecules such as Programmed Cell Death Protein 1 (PD-1) and its Ligand (PD-L1) participate in the immune checkpoint by signaling co-inhibition of lymphocyte responses. In cancers, PD-L1 expression is associated with the immune evasion mechanism, which favors tumor growth. The use of anti-PD-1/PD-L1 drugs is already well described in solid tumors, but still not fully understood in hematologic malignancies. Myelodysplastic neoplasms (MDSs) are heterogeneous bone marrow disorders with an increased risk of progression to Acute Myeloid Leukemia (AML). The MDS affects hematopoietic stem cells and its pathogenesis is linked to genetic and epigenetic defects, in addition to immune dysregulation. The influence of the PD-L1 on the MDS remains unknown. Methods: In this study, we evaluated the mRNA expression of the PD-L1 in 53 patients with MDS, classified according to the WHO 2016 Classification. Results: Patients with dyserythropoiesis presented significantly higher PD-L1 expression than patients without dyserythropoiesis (p = 0.050). Patients classified as having MDS with an excess of blasts 2 (MDS-EB2) presented a significant upregulation in the mRNA expression of the PD-L1 compared to the MDS with an excess of blasts 1 (MDS-EB1) (p = 0.050). Furthermore, we detected three patients with very high levels of PD-L1 expression, being statistically classified as outliers. Conclusion: We suggested that the high expression of the PD-L1 is associated with a worse prognosis in the MDS and functional studies are necessary to evaluate the possible use of anti-PD-L1 therapies for high-risk MDS, such as the MDS-EBs.

Hardware-based acceleration approaches for Machine Learning (ML) workloads have been embracing the significant potential of post-CMOS switching devices to attain reduced footprint and/or energy-efficient execution relative to transistor-based GPU and/or TPU-based accelerator architectures. Meanwhile, the promulgation of fabless IC chip manufacturing paradigms has heightened the hardware security concerns inherent in such approaches. Namely, unauthorized access to various supply chain stages may expose significant vulnerabilities resulting in malfunctions including subtle adversarial outcomes via the malicious generation of differentially-corrupted outputs. Whereas the Spin-Orbit Torque Magnetic Tunnel Junction (SOT-MTJ) is a leading spintronic device for use in ML accelerators, as well as holding security tokens, their manufacturing-only security exposures are identified and evaluated herein. Results indicate a novel vulnerability profile whereby an adversary without access to the circuit netlist could differentially-influence the machine learning application’s behavior. Specifically, ML recognition outputs can be significantly swayed via a global modification of oxide thickness (Tox) resulting in bit-flips of the weights in the crossbar array, thus corrupting the recognition of selected digits in MNIST dataset differentially creating an opportunity for an adversary. With just 0.05% of bits in crossbar having a flipped resistance state, digits “4” and “5” show the highest overall error rates, and digit “9” exhibit the lowest impact, with recognition accuracy of digits “2,” “3,” and “8” unaffected by changing the oxide thickness of SOT-MTJs uniformly from 0.75 nm to 1.2 nm without modifying the netlist nor even having access to the circuit design itself. Exposures and mitigation approaches to such novel and potentially damaging manufacturing-side intrusions are identified, postulated, and quantitatively assessed.

Summary: The striatum integrates dopaminergic and glutamatergic inputs to select preferred versus alternative actions. However, the precise mechanisms underlying this process remain unclear. One way to study action selection is to understand how it breaks down in pathological states. Here, we explored the cellular and synaptic mechanisms of levodopa-induced dyskinesia (LID), a complication of Parkinson’s disease therapy characterized by involuntary movements. We used an activity-dependent tool (FosTRAP) in conjunction with a mouse model of LID to investigate functionally distinct subsets of striatal direct pathway medium spiny neurons (dMSNs). In vivo, levodopa differentially activates dyskinesia-associated (TRAPed) dMSNs compared to other dMSNs. We found this differential activation of TRAPed dMSNs is likely to be driven by higher dopamine receptor expression, dopamine-dependent excitability, and excitatory input from the motor cortex and thalamus. Together, these findings suggest how the intrinsic and synaptic properties of heterogeneous dMSN subpopulations integrate to support action selection.

Objective To evaluate the long-term sustainability of response to the Janus kinase inhibitor upadacitinib among patients with rheumatoid arthritis and an inadequate response or intolerance to biological disease-modifying antirheumatic drugs (bDMARD-IR) in the SELECT-BEYOND phase 3 trial.Methods Patients on background conventional synthetic DMARDs (csDMARDs) were treated once daily with upadacitinib 15 mg or placebo. Patients who completed the week 24 visit could enter a long-term extension of up to 5 years. The sustainability of response was assessed based on achievement of Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and Disease Activity Score 28-joint count using C-reactive protein (DAS28 (CRP)) targets and evaluated up to week 260 in all patients receiving the approved upadacitinib 15 mg dose, including those randomised to upadacitinib 15 mg and those who switched from placebo to upadacitinib 15 mg at week 12.Results In this bDMARD-IR population, 45% (n=104/229) and 79% (n=172/219) of patients treated with upadacitinib 15 mg plus background csDMARD(s) achieved CDAI remission or CDAI low disease activity (LDA) at any point during the 5-year study, respectively. Of those who achieved CDAI remission/LDA, 25%/43% maintained their initial response through 240 weeks of follow-up after first achieving response. Most patients who lost remission or LDA were able to recapture that response by the cut-off date. Similar overall results were observed for SDAI and DAS28 (CRP). No strong predictors of response were identified.Conclusions Over three-quarters of bDMARD-IR patients achieved CDAI LDA with upadacitinib, and almost half of those maintained LDA through 240 weeks of follow-up. Remission was achieved by nearly half of all patients and maintained in approximately a quarter of those achieving remission.Trial registration number NCT02706847.

Background Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort.Methods Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up.Results Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1).Conclusion Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

Objective This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA).Methods This report included 793 participants with untreated early RA from the randomised, longitudinal NORD-STAR trial, all of whom had their body mass index (BMI) assessed at baseline. Obesity was defined as BMI ≥30 kg/m2. All participants were randomised 1:1:1:1 to one of four treatment arms: active conventional treatment, certolizumab-pegol, abatacept and tocilizumab. Clinical and laboratory measurements were performed at baseline and at 8, 12, 24 and 48-week follow-up. The primary endpoint for this report was response to treatment based on Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission and Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP)

Abstract Remission is the established therapeutic goal for patients with systemic lupus erythematosus (SLE) and is currently defined by the widely adopted Definition Of Remission In SLE (DORIS) criteria. Attainment of remission is rare in the clinical setting, thus an alternative, pragmatic treatment target of low disease activity, as defined by the Lupus Low Disease Activity State (LLDAS), provides a less stringent and more attainable treatment goal for a wider proportion of patients compared with DORIS remission. Randomized controlled trials and real-world analyses have confirmed the positive clinical benefits of achieving either DORIS remission or LLDAS. The treat-to-target (T2T) approach utilizes practical clinical targets to proactively tailor individual treatment regimens. Studies in other chronic inflammatory diseases using the T2T approach demonstrated significantly improved clinical outcomes and quality-of-life measures compared with established standard of care. However, such trials have not yet been performed in patients with SLE. Here we review the evolution of DORIS remission and LLDAS definitions and the evidence supporting the positive clinical outcomes following DORIS remission or LLDAS attainment, before discussing considerations for implementation of these outcome measures as potential T2T objectives. Adoption of DORIS remission and LLDAS treatment goals may result in favorable patient outcomes compared with established standard of care for patients with SLE.

Managing annual row crops on marginally productive croplands can be environmentally unsustainable and result in variable economic returns. Incorporating perennial bioenergy feedstocks into marginally productive cropland can engender ecosystem services and enhance climate resiliency while also diversifying farm incomes. We use one of the oldest bioenergy-specific field experiments in North America to evaluate economically and environmentally sustainable management practices for growing perennial grasses on marginal cropland. This long-term field trial called 9804 was established in 1998 in eastern Nebraska and compared the productivity and sustainability of corn (Zea mays L.)—both corn grain and corn stover—and switchgrass (Panicum virgatum L.) bioenergy systems under different harvest strategies and nitrogen (N) fertilizer rates. This experiment demonstrated that switchgrass, compared to corn, is a reliable and sustainable bioenergy feedstock. This experiment has been a catalyst for other bioenergy projects which have also expanded our understanding of growing and managing bioenergy feedstocks on marginal cropland. We (1) synthesize research from this long-term experiment and (2) provide perspective concerning both the knowledge gained from this experiment and knowledge gaps and how to fill them as well as the role switchgrass will play in the future of bioenergy.

Despite the continued improvements in pancreas transplant outcomes in recent decades, a subset of recipients experience graft failure and can experience substantial morbidity and mortality. Here, we summarize what is known about the failed pancreas allograft and what factors are important for consideration of retransplantation. The current definition of pancreas allograft failure and its challenges for the transplant community are explored. The impacts of a failed pancreas allograft are presented, including patient survival and resultant morbidities. The signs, symptoms, and medical and surgical management of a failed pancreas allograft are described, whereas the options and consequences of immunosuppression withdrawal are reviewed. Medical and surgical factors necessary for successful retransplant candidacy are detailed with emphasis on how well-selected patients may achieve excellent retransplant outcomes. To achieve substantial medical mitigation and even pancreas retransplantation, patients with a failed pancreas allograft warrant special attention to their residual renal, cardiovascular, and pulmonary function. Future studies of the failed pancreas allograft will require improved reporting of graft failure from transplant centers and continued investigation from experienced centers.

The study found that maximum precipitation and water retention occur in February for the Cacao sector and in October and February for the Caliza sector, with minimum values in July. The correlation between precipitation and temperature is −0.43 for both sectors, while the negative correlation between retentivity and temperature is stronger in the Caliza sector (−0.467) than in the Cacao sector (−0.096). Precipitation explains 82.07% and 89.92% of the variability in retentivity for the Cacao and Caliza sectors, respectively, according to the R2 coefficients. The environmental impact analysis indicates a medium impact with a value of 5.6.

Introduction: A simple visual score based on chest computed tomography (CT) findings is desirable for defining prognosis in patients with COVID-19 pneumonia. This study evaluated the diagnostic performance of chest CT using a visual quantification score of lung involvement that predicts the clinical outcome and management area of patients with COVID-19 pneumonia. We also compared the accuracy of this score with clinical severity scores and inflammatory markers. Materials and methods: A chest CT quantitative evaluation (CT-QE) ranging from 0 to 15 points was created. Scores were found to be correlated with the patient management areas such as home, hospital ward, and intensive care unit (ICU). Receiver operating characteristic (ROC) curves were compared with the diagnostic performance of the CT-QE score with clinical severity scales and inflammatory markers to predict clinical outcomes. Results: A total of 178 patients with COVID-19 pneumonia were included. The CT-QE score (AUC, 0.78) had a higher accuracy for adverse clinical outcomes than the CURB-65 score (AUC, 0.65) and the P/F ratio (AUC, 0.69) (p < 0.001). Furthermore, the CT-QE score (AUC, 0.86) outperformed CRP (AUC, 0.77), D-dimer (AUC, 0.73), and ferritin (AUC, 0.76) (p < 0.001) in predicting the clinical outcomes. The CT-QE score was 6-9 points for hospital ward management (p < 0.001) and ≥ 10 points for admission to the ICU or death (p < 0.001). Conclusion: The CT-QE score is a simple and practical visual quantification tool based on chest CT findings for prognosis, which predicts the clinical outcome and management area in patients with COVID-19 pneumonia.

Objective Evidence indicates reduced treatment effectiveness of TNFi in women with axial spondyloarthritis (axSpA) compared with men. We aimed to investigate sex differences in treatment response and retention rates over 24 months of follow-up in axSpA patients initiating their first TNFi.Methods Data from axSpA patients initiating a TNFi in 1 of 15 registries within EuroSpA collaboration were pooled. We investigated the association of sex with treatment response using logistic regression. The primary outcome was clinically important improvement (CII) at 6 months according to Ankylosing Spondylitis Disease Activity Score with C-reactive protein (CRP) (≥1.1 decrease). We adjusted for age, country and TNFi start year. A secondary outcome was retention rates over 24 months of follow-up assessed by Kaplan-Meier estimator.Results In total, 6451 axSpA patients with data on CII were assessed for treatment response; 2538 (39%) were women and 3913 (61%) were men. Women presented at baseline with lower CRP levels but had higher scores on patient-reported outcome measures. At 6 months, 53% of the women and 66% of the men had CII. Women had a lower relative risk of CII compared with men (0.81; 95% CI 0.77 to 0.84). This sex difference was similar in adjusted analysis (0.85; 95% CI 0.82 to 0.88). Retention rates were evaluated in 27 702 patients. The TNFi 6/12/24 months retention rates were significantly lower among women (79%/66%/53%) than men (88%/79%/69%).Conclusion Treatment response and retention rates are lower among women with axSpA initiating their first TNFi. Sex differences in treatment effectiveness were present regardless of the outcome measure used for treatment response, and differences in retention rates transpired early and increased as time progressed.

The dynamic complexity and individualization of running biomechanics has challenged the development of objective and comparative gait measures. Here, we present and explore several novel biomechanical metrics for running that are informed by a canonical inter-species gait template–the spring-mass model. The measures assess running mechanics systemically against the template via quantifying characteristics of a runner’s kinetics relative to the energy-conserving elastic system–i.e., their “spring-mass similarity”. Applying these metrics in a retrospective cohort investigation, we studied the overground kinetics of two heterogenous populations of runners in two footwear conditions: elite and recreational athletes in shod and barefoot conditions. Across all measures and within foot strike types, the elite runners exhibited mechanics that were more similar to those of the ideally elastic spring-mass template. The elite runners had more symmetric bounces, less discrepancy (i.e., greater coordination) between horizontal and vertical kinetic changes, and better fit to a spring-mass vertical ground reaction force time series. Barefoot running elicited greater kinetic coordination in the recreational runners. At a faster speed, the elites further improved their similarity to the template. Overall, the more economical elite group exhibited greater likeness to the linearly elastic, energy-conserving spring-mass system than their recreational counterparts. This study introduces novel biomechanical measures related to performance in distance running. More broadly, it provides new, approachable metrics for systemic quantification of gait biomechanics in runners across all demographics. These metrics may be applied to assess a runner’s global biomechanical response to a variety of interventions, including training adaptations, rehabilitation programs, and footwear conditions.

Given several different populations, the relative proportions of each in the high (or low) end of the distribution of a given characteristic are often more important than the overall average values or standard deviations. In the case of two different normally-distributed random variables, as is shown here, one of the (right) tail ratios will not only eventually be greater than 1 from some point on, but will even become infinitely large. More generally, in every finite mixture of different normal distributions, there will always be exactly one of those distributions that is not only overrepresented in the right tail of the mixture but even completely overwhelms all other subpopulations in the rightmost tails. This property (and the analogous result for the left tails), although not unique to normal distributions, is not shared by other common continuous centrally symmetric unimodal distributions, such as Laplace, nor even by other bell-shaped distributions, such as Cauchy (Lorentz) distributions.

California Leafy Green Products Handler Marketing Agreement (LGMA) established food safety metrics with guidance recommendations of 366 m (1,200 feet) and 1,609 m (1 mile) distances between production fields of leafy greens and a concentrated animal feeding operation (CAFO) containing >1,000 and >80,000 head of cattle, respectively. This study evaluated the effect of these distance metrics and environmental factors on the occurrence of airborne Escherichia coli in proximity to seven commercial beef cattle feedlots located in Imperial Valley, California. A total of 168 air samples were collected from seven beef cattle feedlots during March and April 2020, which were the months implicated in the 2018 Yuma Arizona lettuce outbreak of E. coli O157:H7. The distance between air sampling sites and the edge of the feedlot ranged from ∼0 to ∼2,200 m (∼1.3 mile), with each sample comprised of 1,000 L of processed air taken at a 1.2 m elevation over a 10-minute duration. E. coli colonies were enumerated on CHROMagar ECC selective agar and confirmed with conventional PCR. Meteorological data (air temperature, wind speed, wind direction, relative humidity) were collected in situ. The prevalence and mean concentration of E. coli were 6.55% (11/168) and 0.09 CFU per 1,000 L of air, with positive samples limited to within 37 m (120 ft) of the feedlot. Based on logistic regression, the odds of airborne E. coli detection were associated with little to no wind and close proximity to a feedlot. This pilot study found limited dispersal of airborne E. coli in proximity to commercial feedlots in Imperial Valley, with light-to-no wind and proximity within 37 m of a feedlot significant factor-associated airborne E. coli in this produce-growing region of California.

Common envelope evolution (CEE) is vital for forming short-orbital-period compact binaries. It covers many objects, such as double compact merging binaries, Type Ia supernovae progenitors, binary pulsars, and X-ray binaries. Knowledge of the common envelope (CE) ejection efficiency still needs to be improved, though progress has been made recently. Short-orbital-period hot subdwarf B star (sdB) plus white dwarf (WD) binaries are the most straightforward samples with which to constrain CEE physics. We apply the known orbital period–WD mass relation to constrain the sdB progenitors of seven sdB+WD binaries with a known inclination angle. The average CE efficiency parameter is 0.32. This is consistent with previous studies. However, the CE efficiency need not be constant, but a function of the initial mass ratio, based on well-constrained sdB progenitor mass and evolutionary stage. Our results can be used as physical inputs for binary population synthesis simulations of related objects. A similar method can also be applied to study other short-orbital-period WD binaries.

Environmental cues (e.g. achievement-related words and pictures) can prime/activate, in the absence of awareness, a mental representation of importance stored in memory. Chen et al.'s 2021 Applied Psychology: An International Review 70, 216–253. (doi:10.1111/apps.12239) meta-analysis revealed a moderate, significant overall effect for the goal priming-organizational behaviour relationship, with three moderators identified: context-specific versus a general prime, prime modality (i.e. visual versus linguistic) and experimental setting (field versus laboratory). An independent researcher found that their finding was negligibly affected by a publication bias. Shanks & Vadillo (2021), Royal Society Open Science 8, 210544. (doi:10.1098/rsos.210544) (field: k = 13, N = 683, d = 0.64), questioned Chen et al.'s conclusion regarding the effect size found in field studies (field: k = 8, N = 357, d = 0.68). In this paper, we discussed Shanks & Vadillo's selection of additional field experiments that led to their conclusion of a publication bias. We updated Chen et al.'s meta-analysis to include relevant studies conducted since that study's publication. The present meta-analysis reproduced the original findings in Chen et al. (field: k = 11, N = 534, d = 0.67). The updated findings are consistent with: (i) laboratory findings, (ii) the findings obtained in field experiments on consciously set goals and (iii) goal setting theory (Latham & Locke, 2018 In Handbook of industrial, work & organizational Psychology, vol. 1 (eds D Ones, N Anderson, C Viswesvaran, H Sinangil), pp. 103–124).

BackgroundSoil-derived prokaryotic gut communities of the Japanese beetle Popillia japonica Newman (JB) larval gut include heterotrophic, ammonia-oxidizing, and methanogenic microbes potentially capable of promoting greenhouse gas (GHG) emissions. However, no research has directly explored GHG emissions or the eukaryotic microbiota associated with the larval gut of this invasive species. In particular, fungi are frequently associated with the insect gut where they produce digestive enzymes and aid in nutrient acquisition. Using a series of laboratory and field experiments, this study aimed to (1) assess the impact of JB larvae on soil GHG emissions; (2) characterize gut mycobiota associated with these larvae; and (3) examine how soil biological and physicochemical characteristics influence variation in both GHG emissions and the composition of larval gut mycobiota.MethodsManipulative laboratory experiments consisted of microcosms containing increasing densities of JB larvae alone or in clean (uninfested) soil. Field experiments included 10 locations across Indiana and Wisconsin where gas samples from soils, as well as JB and their associated soil were collected to analyze soil GHG emissions, and mycobiota (ITS survey), respectively.ResultsIn laboratory trials, emission rates of CO2, CH4, and N2O from infested soil were ≥ 6.3× higher per larva than emissions from JB larvae alone whereas CO2 emission rates from soils previously infested by JB larvae were 1.3× higher than emissions from JB larvae alone. In the field, JB larval density was a significant predictor of CO2 emissions from infested soils, and both CO2 and CH4 emissions were higher in previously infested soils. We found that geographic location had the greatest influence on variation in larval gut mycobiota, although the effects of compartment (i.e., soil, midgut and hindgut) were also significant. There was substantial overlap in the composition and prevalence of the core fungal mycobiota across compartments with prominent fungal taxa being associated with cellulose degradation and prokaryotic methane production/consumption. Soil physicochemical characteristics such as organic matter, cation exchange capacity, sand, and water holding capacity, were also correlated with both soil GHG emission, and fungal a-diversity within the JB larval gut. Conclusions: Results indicate JB larvae promote GHG emissions from the soil directly through metabolic activities, and indirectly by creating soil conditions that favor GHG-associated microbial activity. Fungal communities associated with the JB larval gut are primarily influenced by adaptation to local soils, with many prominent members of that consortium potentially contributing to C and N transformations capable of influencing GHG emissions from infested soil.

Introduction EXCELLENT (NCT03685578; Cerenovus) is a large, prospective, international, real‐world registry of endovascular clot removal in acute ischemic stroke (AIS) with EmboTrap as the first line mechanical thrombectomy (MT) device, which included collection and analysis of the retrieved thrombus material. Methods Between September 2018 and March 2021, 1000 “all‐comer” patients were enrolled at 34 global sites (27 US, 5 EU, 1 UK, 1 Israel) and treated according to standard of care at each center (with Embrotrap as first line). The study employed blind endpoint evaluation, including a core imaging lab and an independent 90‐day mRS assessment. Retrieved clot was collected per each MT maneuver from 538 subjects across 26 sites and clot analysis was performed by independent central labs blinded to clinical data. Results mITT population included 998 subjects. Mean age was 69.9±14.18 years (range 18–102), 51.8% (517/998) subjects were female and 9.9% (97/997) had a pre‐stroke mRS 3–5. Baseline NIHSS was 15.6±6.87 (range 0–36); 10.1% (82/815) subjects had a large core (ASPECTS 0–5); 5.8% (57/990) had posterior stroke; 56.3% (523/929) underwent MT ≤ 6hrs of onset and 38.1% (380/998) received IV‐tPA prior to MT. First pass eTICI 2c‐3 was achieved in 38.3% (377/984) and final 2b‐3 in 94.5 % (930/984; median number of passes = 1) of subjects. 90‐day mRS≤2 or ≤pre‐stroke was 46.9% (429/915) and 90‐day all‐cause mortality was 19.0% (175/921). The univariate analysis of clot components showed high red blood cell and low platelet content were significant predictors of good mRS outcome (p

Abstract Background Patients with systemic lupus erythematosus (SLE) have substantial unmet medical need. Baricitinib is a Janus kinase (JAK)1 and 2 inhibitor that was shown to have therapeutic benefit in patients with SLE in a phase II clinical trial. The purpose of this study was to evaluate the median change from baseline in conventional serologic biomarkers in subgroups and the overall population of baricitinib-treated patients with SLE, and the SLE Responder Index-4 (SRI-4) response by normalization of anti-dsDNA. Methods Data were assessed from the phase II trial I4V-MC-JAHH (NCT02708095). The median change from baseline in anti-dsDNA, IgG, and other conventional serologic markers was evaluated over time in patients who had elevated levels of markers at baseline, and in all patients for IgG. Median change from baseline for baricitinib treatments were compared with placebo. Among patients who were anti-dsDNA positive at baseline, SRI-4 responder rate was compared for those who stayed positive or achieved normal levels by week 24. Results Significant decreases of anti-dsDNA antibodies were observed in response to baricitinib 2 mg and 4 mg compared to placebo beginning at weeks 2 (baricitinib 2 mg = − 14.3 IU/mL, placebo = 0.1 IU/mL) and 4 (baricitinib 4 mg = − 17.9 IU/mL, placebo = 0.02 IU/mL), respectively, continuing through week 24 (baricitinib 2 mg = − 29.6 IU/mL, baricitinib 4 mg = − 15.1 IU/mL, placebo=3.0 IU/mL). Significant reductions from baseline of IgG levels were found for baricitinib 4 mg-treated patients compared to placebo at weeks 12 (baricitinib 4 mg = − 0.65 g/L, placebo = 0.09 g/L) and 24 (baricitinib 4 mg = − 0.60 g/L, placebo = − 0.04 g/L). For patients who were anti-dsDNA positive at baseline, no relationship between achieving SRI-4 responder and normalization of anti-dsDNA was observed by week 24. Conclusions Baricitinib treatment resulted in a rapid and sustained significant decrease in anti-dsDNA antibodies compared to placebo among those with positive anti-dsDNA antibodies at baseline, as well as a significant decrease in IgG levels in the 4 mg group at weeks 12 and 24. These data suggest that baricitinib may influence B cell activity in SLE. Further studies are needed to evaluate if reductions in anti-dsDNA levels with baricitinib treatment reflect the impact of baricitinib on B cell activity. Trial registration NCT02708095 .

Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome measures to accelerate development of lupus therapeutics.

Background Systems of care surrounding endovascular therapy for stroke have garnered much attention in recent years. In‐hospital metrics, such as “door‐to‐puncture” and procedure times have been areas for quality improvement. The temporal trend and clinical significance of prehospital “onset‐to‐door” time, however, remains unknown. Methods We performed a systematic review of time metric data from all published randomized controlled and investigational device exemption trials involving endovascular therapy for stroke between 2005 and 2019 (n=26). Second, we conducted a record‐level observational analysis on a total of 3512 patients from 3 real‐world registries (Mechanical Embolus Removal in Cerebral Ischemia [MERCI], Thrombectomy REvascularization of Large Vessel Occlusions in Acute Ischemic Stroke [TREVO], and TREVO Stent‐Retriever Acute Stroke [TRACK]), together with 4 prospective trials (MERCI trial, Multi‐MERCI, TREVO‐EU, and TREVO‐2). Only patients receiving mechanical thrombectomy within 9 hours from onset‐to‐puncture time were included. Predictors of good outcome were identified using generalized linear mixed modeling. Results Door‐to‐puncture times (slope=−5.83 min/y; R2=0.25; P=0.046), procedure times (slope=−3.78 min/y; R2=0.54; P

The impact of agro-industrial waste can be reduced by using it in crop fertilization. The aim of this study was to evaluate the stomatal density and yield of radish (Raphanus Sativus L.) fertilized with biol at different concentrations, produced from sugar cane residues. A completely randomized blocks design statistical model was used, which consisted of 5 tests with 3 repetitions for each one, being T1 the control trial, and T2, T3, T4 and T5 the treatments using 2, 3, 4 and 5 L of biol in 200 L of water respectively. In terms of crop physical characteristics, the T5 treatment excelled in plant length, equatorial diameter, plant weight, as well as yield with 12.71 t/ha. Likewise, in the chemical analysis of the radish leaves, the T5 treatment showed an increase in K, Ca, Zn and MN, while the T2 did it in N, P and Cu, the T3 in Fe and the T4 in Mg. In terms of stomatal density, T5 stood out with 122 stomatal/mm2. Based on this, it is concluded that the increase in the dose of biol influences the increase in nutrient and stomatal density and hence the yield of the radish crop.

This research aims to determine the effect of activated carbon obtained from cocoa husks (Theobroma cacao L.) on the adsorption of iron (II) present in water of an aquifer for human consumption. Charcoal was prepared at different carbonization temperatures (500, 600 and 700 °C) for 30 minutes and activated with phosphoric acid in the proportions of 1:1. Iron (II) adsorption was determined as a function of variations in mixing speed, contact time, charcoal dosage and stirring speed. It was determined that, over the range considered, agitation speeds had no significant effect on the percentage of iron (II) removal, being the dose of activated carbon and temperature, the most influential variables. The water samples had an initial iron concentration of 3.15 mg/L and 4 mg/L. The best iron (II) adsorption result was obtained with activated carbon at the carbonization temperature of 700 °C, with a mass of 1.5 g of carbon, with efficiencies of 93 % and 98 % for both samples considered. Based on the results, it was concluded water for human consumption is treatable with activated carbon derived from Theobroma cacao L. for the adsorption of iron (II), considering that this parameter is below the maximum limit of 0.3 mg/L allowed by current regulations.

We used principal component analysis (PCA) to examine the component structure of a neuropsychological test battery administered to 943 cognitively-normal adults enrolled in the Southern Illinois University (SIU) Longitudinal Cognitive Aging Study (LCAS). Four components explaining the most variance (63.9%) in the dataset were identified: speed/cognitive flexibility, visuospatial skills, word-list learning/memory, and story memory. Regression analyses confirmed that increased age was associated with decreased component scores after controlling for gender and education. Our identified components differ slightly from previous studies using PCA on similar test batteries. Factors such as the demographic characteristics of the study sample, the inclusion of mixed patient and control samples, the inclusion of different test measures in previous studies, and the fact that many neuropsychological test measures assess multiple cognitive processes simultaneously, may help to explain these inconsistencies.

For higher yields in vegetable cultivation, the availability of soil nutrients must be improved. Therefore, the aim of this research was to establish the relationship between stomatal density and the yield of the radish crop fertilized with compost made from organic market waste. A completely randomized block design was used, which consisted of 3 blocks and 5 treatments, which were T1, T2, T3, T4 and T5 with 00, 10, 15, 15, 20 and 25 g compost/plant respectively. The physical characteristics of the plants were evaluated from sowing to harvest and the data obtained were processed by analysis of variance and Duncan's test. Chemical analysis of the compost and soil was carried out, as well as a foliar analysis to determine the nutrient concentration by treatment. The results determined that the treatment (T4) stood out in plant length with 28.96 cm, plant weight with 43.33 g, yield of 10.82 t/ha and bulb diameter of 3.92 cm; likewise, in the concentration of nutrients in the leaves, the treatment (T5) highlighted in N with 5.94%, Ca 4.84%, Mg 1.29%, Zn 64.58 ppm and a stomatal density of 642 stomas/mm2. It is concluded that, at an adequate dose of compost, the concentration of nutrients increases, as well as the stomatal density, resulting in higher yields.

A study was conducted to identify balsam fir (Abies balsamea) for use in Christmas tree breeding programs in Northeastern North America. A total of sixty-four phenotypically good trees were identified from a provincial clonal seed orchard in New Brunswick, a multi-aged natural seed production area in Nova Scotia, and an operational plantation in Quebec, Canada. Trees were selected for good growth and form, numbers, and vigour of internodal branches, acceptable crown taper, needle colour, age class, branch angle, needle configuration, and freedom from insects and diseases or deformities, all traits deemed desirable in a Christmas tree. Three branches from each tree were collected at two harvest dates each year, one early and one late during the normal harvesting season in 2020, 2021, and 2022. Qualitative assessments of colour and branch pliability were performed weekly in conjunction with needle loss rub tests. A quantitative assessment of moisture loss was conducted weekly by measuring branch weights. The combination of qualitative and quantitative assessments was used to identify 7 of the 64 trees for which one or more tested branches consistently remained green and pliable, retained the majority of their needles, and lost moisture at a significantly reduced rate in all six testing periods. Grafts of the seven ‘Select’ trees are currently being integrated into seed orchards in the three participating provinces. These second-generation seed orchards are part of breeding programs designed to develop Christmas trees that will perform well under warm fall conditions, an outcome of climate change. The results from this study combined with the progeny testing of the ‘Select’ trees will be used to test for the heritability of needle retention, a key trait for the next generation of Christmas trees in the Northeast.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by dysplasias, ineffective hematopoiesis and risk of acute myeloid leukemia transformation. Approximately 90% of MDS patients present mutations in genes involved in various cell signaling pathways. Specialized DNA polymerases, such as POLN, POLI, POLK, POLQ, POLH, POLL and REV3L, insert a nucleotide opposite replication–blocking DNA lesions in an error-prone manner and, in this way, sometimes can actively promote the generation of mutation. For the best of our knowledge, has not been described the mutations of these genes in MDS. DNA target sequencing CDS regions of the REV3L gene was performed in a 58-year-old man diagnosed as High Risk Myelodysplastic Syndrome. The patient presented very low hemoglobin, increased number of blasts, karyotype:47,XY,+8[6]/47,XY,del(7)(q32),+8[7], no response to hypomethylating therapy (decitabine), all markers of poor prognosis. Target sequencing identified a mutation c.9253-6T>C REV3L (Substitution - intronic) with VAF (variant allele frequency) = 16% considered pathogenic according to Functional Analysis through. Hidden Markov Models (FATHMM). This is the first evidence of REV3L mutation in MDS and, of utmost importance, associated with poor prognosis.

Abstract Background A substantial proportion of rheumatoid arthritis (RA) patients discontinues treatment with tumour necrosis factor inhibitors (TNFi) due to inefficacy or intolerance. After the failure of treatment with a TNFi, treatment can be switched to another TNFi or a bDMARD with a different mode of action (non-TNFi). Measurement of serum drug concentrations and/or anti-drug antibodies (therapeutic drug monitoring (TDM)) may help to inform the choice for the next step. However, the clinical utility of TDM to guide switching has not been investigated in a randomised test-treatment study. Methods ADDORA-switch is a 24-week, multi-centre, triple-blinded, superiority test-treatment randomised controlled trial. A total of 84 RA patients failing adalimumab treatment (treatment failure defined as DAS28-CRP > 2.9) will be randomised in a 1:1 ratio to a switching strategy to either TNFi or non-TNFi based on adalimumab serum trough level (intervention group) or random allocation (control group). The primary outcome is the between-group difference in mean time-weighted DAS28 over 24 weeks. Discussion The trial design differs in many aspects from previously published and ongoing TDM studies and is considered the first blinded test-treatment trial using TDM in RA. Several choices in the design of this trial are described, and overarching principles regarding test-treatment trials and clinical utility of TDM are discussed in further detail. Trial registration Dutch Trial Register NL8210 . Registered on 3 December 2019 (CMO NL69841.091.19).

The aim of this research was to determine the efficiency of activated carbon obtained from coconut (Cocos nucifera) endocarp in the reduction of color in runoff water to improve its quality. For this purpose, activated carbon was produced at a carbonization temperature of 700 °C in a time of 30 minutes and phosphoric acid at a concentration of 85% was used as an activating agent. A completely randomized design was used, consisting of 3 treatments (100, 50 and 25 g of activated carbon) and a control (without treatment), with three replicates of each treatment, where 1 L of water from the uptake was filtered. It was determined that the best percentage removal was obtained with treatment 3 (T3) in the reduction of color and turbidity with average values of 97.56% and 97.11%, respectively. An activated carbon filter was installed in the San Lorenzo - Moyobamba sector in a similar way to the laboratory tests, in which the efficiency of this product in reducing the color and turbidity of the water was demonstrated, achieving values suitable for human consumption.

Myelodysplastic syndrome (MDS) is a hematological disorder characterized by abnormal stem cell differentiation and a high risk of acute myeloid leukemia transformation. Treatment options for MDS are still limited, making the identification of molecular signatures for MDS progression a vital task. Thus, we evaluated the proteome of bone marrow plasma from patients (n = 28) diagnosed with MDS with ring sideroblasts (MDS-RS) and MDS with blasts in the bone marrow (MDS-EB) using label-free mass spectrometry. This strategy allowed the identification of 1,194 proteins in the bone marrow plasma samples. Polyubiquitin-C (UBC), moesin (MSN), and Talin-1 (TLN1) showed the highest abundances in MDS-EB, and centrosomal protein of 55 kDa (CEP55) showed the highest relative abundance in the bone marrow plasma of MDS-RS patients. In a follow-up, in the second phase of the study, expressions of UBC, MSN, TLN1, and CEP55 genes were evaluated in bone marrow mononuclear cells from 45 patients by using qPCR. This second cohort included only seven patients from the first study. CEP55, MSN, and UBC expressions were similar in mononuclear cells from MDS-RS and MDS-EB individuals. However, TLN1 gene expression was greater in mononuclear cells from MDS-RS (p = 0.049) as compared to MDS-EB patients. Irrespective of the MDS subtype, CEP55 expression was higher (p = 0.045) in MDS patients with abnormal karyotypes, while MSN, UBC, and TALIN1 transcripts were similar in MDS with normal vs. abnormal karyotypes. In conclusion, proteomic and gene expression approaches brought evidence of altered TLN1 and CEP55 expressions in cellular and non-cellular bone marrow compartments of patients with low-risk (MDS-RS) and high-risk (MDS-EB) MDSs and with normal vs. abnormal karyotypes. As MDS is characterized by disrupted apoptosis and chromosomal alterations, leading to mitotic slippage, TLN1 and CEP55 represent potential markers for MDS prognosis and/or targeted therapy.

The preclinical phase of autoimmune disorders is characterized by an initial asymptomatic phase of varying length followed by nonspecific signs and symptoms. A variety of autoimmune and inflammatory manifestations can be present and tend to increase in the last months to years before a clinical diagnosis can be made. The phenotype of an autoimmune disease depends on the involved organs, the underlying genetic susceptibility and pathophysiological processes. There are different as well as shared genetic or environmental risk factors and pathophysiological mechanisms between separate diseases. To shed more light on this, in this narrative review we compare the preclinical disease course of four important autoimmune diseases with distinct phenotypes: rheumatoid arthritis (RA), Systemic Lupus Erythematosus (SLE), multiple sclerosis (MS) and type 1 diabetes (T1D). In general, we observed some notable similarities such as a North-South gradient of decreasing prevalence, a female preponderance (except for T1D), major genetic risk factors at the HLA level, partly overlapping cytokine profiles and lifestyle risk factors such as obesity, smoking and stress. The latter risk factors are known to produce a state of chronic systemic low grade inflammation. A central characteristic of all four diseases is an on average lengthy prodromal phase with no or minor symptoms which can last many years, suggesting a gradually evolving interaction between the genetic profile and the environment. Part of the abnormalities may be present in unaffected family members, and autoimmune diseases can also cluster in families. In conclusion, a promising strategy for prevention of autoimmune diseases might be to address adverse life style factors by public health measures at the population level.

Although several factors influence Hispanic Latina/o/x degree attainment, less is known regarding student-to-faculty ratio at Hispanic-Serving Institutions (HSI) in Florida. We examined publicly available data for HSI (n = 14) and non-HSI (n = 88) degree attainment among Hispanic Latina/o/x students in Florida. Pearson correlations and regression analyses indicated statistically significant correlations between student-to-faculty ratio and Hispanic Latino/a/x students who earned bachelor's degrees. Implications for hiring and promotion are discussed.

Abstract Background Soil microbial communities cope with an imbalanced supply of resources by adjusting their element acquisition and utilization strategies. Although soil pH has long been considered an essential driver of microbial growth and community composition, little is known about how soil acidification affects microbial acquisition and utilization of carbon (C) and nitrogen (N). To close the knowledge gap, we simulated soil acidification and created a pH gradient by adding eight levels of elemental sulfur (S) to the soil in a meadow steppe. Results We found that S-induced soil acidification strongly enhanced the ratio of fungi to bacteria (F:B) and microbial biomass C to N (MBC:MBN) and subsequently decreased the C:N imbalance between microbial biomass and their resources. The linear decrease in the C:N imbalance with decreasing soil pH implied a conversion from N limitation to C limitation. To cope with enhanced C versus N limitation, soil microbial communities regulated the relative production of enzymes by increasing the ratio of β-glucosidase (BG, C-acquiring enzyme) to leucine aminopeptidase (LAP, N-acquiring enzyme), even though both enzymatic activities decreased with S addition. Structural equation modeling (SEM) suggested that higher C limitation and C:N-acquiring enzyme stimulated microbial carbon-use efficiency (CUE), which counteracted the negative effect of metal stress (i.e., aluminum and manganese) under soil acidification. Conclusions Overall, these results highlight the importance of stoichiometric controls in microbial adaption to soil acidification, which may help predict soil microbial responses to future acid deposition.

Abstract Elite middle distance runners present as a unique population in which to explore biomechanical phenomena in relation to running speed, as their training and racing spans a broad spectrum of paces. However, there have been no comprehensive investigations of running mechanics across speeds within this population. Here, we used the spring-mass model of running to explore global mechanical behavior across speeds in these runners. Ten elite-level 1500 m and mile runners (mean 1500 m best: 3:37.3 ± 3.6 s; mile: 3:54.6 ± 3.9 s) and ten highly trained 1500 m and mile runners (mean 1500 m best: 4:07.6 ± 3.7 s; mile: 4:27.4 ± 4.1 s) ran on a treadmill at 10 speeds where temporal measures were recorded. Spatiotemporal and spring-mass characteristics and their corresponding variation were calculated within and across speeds. All spatiotemporal measures changed with speed in both groups, but the changes were less substantial in the elites. The elite runners ran with greater approximated vertical forces (+ 0.16 BW) and steeper impact angles (+ 3.1°) across speeds. Moreover, the elites ran with greater leg and vertical stiffnesses (+ 2.1 kN/m and + 3.6 kN/m) across speeds. Neither group changed leg stiffness with increasing speeds, but both groups increased vertical stiffness (1.6 kN/m per km/h), and the elite runners more so (further + 0.4 kN/m per km/h). The elite runners also demonstrated lower variability in their spatiotemporal behavior across speeds. Together, these findings suggested that elite middle distance runners may have distinct global mechanical patterns across running speeds, where they behave as stiffer, less variable spring-mass systems compared to highly trained, but sub-elite counterparts.

This research aims to determine and analyze the law consequences of overmacht in credit agreements due to the Covid-19 Pandemic and as legal remedies for settlement of the credit agreement due to the Covid-19 Pandemic. This research is socio-legal research, a combination research method between doctrinal law research methods and empirical legal research methods. This research was conducted in banking institutions and financing institutions in Ambon City, namely at Bank Mandiri Ambon Branch Office, BCA Ambon Branch Office, Bank Artha Graha Ambon Branch Office, and BFI Limited Company Ambon Branch Office. The types of research data are primary data and secondary data, obtained through literature study and interviews. Based on the results of the research, the Covid-19 Pandemic is a non-natural disaster, so it is categorized as a relative overmacht, so the result of the comparative overmacht law in the credit agreement due to the Covid-19 Pandemic in Ambon City has not changed the risk burden in the sense that the Debtor still fulfills their achievements after the outbreak of Covid - 19 Pandemic is over. The legal effort that can be taken to settle credit agreements due to Covid-19 Pandemic in Ambon City is through credit restructuring in the form of lowering interest rates, extending the period, reducing principal arrears, and reducing interest arrears as determined by the government to be implemented by the bank or financing institutions with debtors.

Two-terminal magnetoresistive random access memory (MRAM) devices provide a recent approach to intrinsically realizing stochastic neuronal behavior in cognitive architectures such as restricted Boltzmann machines (RBMs) for deep belief networks (DBNs). MRAM-based DBNs have achieved substantial energy and area improvements in comparison with the prior DBN hardware implementations. However, MRAM-based DBNs suffer from low accuracy in image classification. In order to resolve this problem, we present a new DBN-fuzzy system based on the combination of MRAM-based DBNs and fuzzy systems in the interest of improving the accuracy of MRAM-based neural networks. First, the MRAM-based DBN is employed to identify the top recognition results with the highest probability. Second, the fuzzy system is utilized to obtain the top-1 recognition results. We assess the accuracy of neural networks on the MNIST dataset, finding that the top-1 accuracy of the DBN-fuzzy neural network is improved from 64% to 82% in comparison to the MRAM-based DBNs for a $784\times10$ network.

Previous research finds that low achievers and students from lower socioeconomic status backgrounds are more likely to bully peers, but fails to satisfactorily explain why. This paper tests the hypothesis that feelings of insecurity mediate the relationship between family background and low achievement, as predictors, and self-perception of being a bully, as the outcome. It operationalizes feelings of insecurity as self-esteem and academic-status insecurity. Using a large and diverse dataset of survey responses from secondary school males in the U.S. (N = 7,291, 45% White, 30% Black, 25% Latino from 6th-12th grade), the paper applies multi-level mediation analyses to test the hypothesis separately for Blacks, Whites, and Latinos. For all three groups, the insecurity measures account for virtually all of the relationship between a grade point average and self-perception of being a bully, and about a third of the relationship between family background and the same bullying measure. Implications are discussed.

BackgroundThe Onduo virtual care program for people with type 2 diabetes (T2D) includes a mobile app, remote lifestyle coaching, connected devices, and telemedicine consultations with endocrinologists for medication management and prescription of real-time continuous glucose monitoring (RT-CGM) devices. In a previously described 4-month prospective study of this program, adults with T2D and baseline glycated hemoglobin (HbA1c) ≥8.0% to ≤12.0% experienced a mean HbA1c decrease of 1.6% with no significant increase in hypoglycemia. ObjectiveThe objective of this analysis was to evaluate medication optimization and management in the 4-month prospective T2D study. MethodsStudy participants received at least 1 telemedicine consultation with an Onduo endocrinologist for diabetes medication management and used RT-CGM intermittently to guide therapy and dosing. Medication changes were analyzed. ResultsOf 55 participants, 48 (87%) had a medication change consisting of a dose change, addition, or discontinuation. Of these, 15 (31%) participants had a net increase in number of diabetes medication classes from baseline. Mean time to first medication change for these participants was 36 days. The percentage of participants taking a glucagon-like peptide-1 receptor agonist increased from 25% (12/48) to 56% (n=27), while the percentages of participants taking a sulfonylurea or dipeptidyl peptidase 4 inhibitor decreased from 56% (n=27) to 33% (n=16) and 17% (n=8) to 6% (n=3), respectively. Prescriptions of other antidiabetic medication classes including insulin did not change significantly. ConclusionsThe Onduo virtual care program can play an important role in providing timely access to guideline-based diabetes management medications and technologies for people with T2D. Trial RegistrationClinicalTrials.gov NCT03865381; https://clinicaltrials.gov/ct2/show/NCT03865381

Acutely, non-selective cannabinoid (CB) agonists have been shown to increase morphine antinociceptive effects, and we and others have also demonstrated that non-selective CB agonists attenuate morphine antinociceptive tolerance. Activation of cannabinoid CB2 receptors reverses allodynia and hyperalgesia in models of chronic pain, and co-administration of morphine with CB2 receptor selective agonists has been shown to be synergistic. CB2 receptor activation has also been shown to reduce morphine-induced hyperalgesia in rodents, an effect attributed to CB2 receptor modulation of inflammation. In the present set of experiments, we tested both the acute and chronic interactions between morphine and the CB2 receptor selective agonist O-1966 treatments on antinociception and antinociceptive tolerance in C57Bl6 mice. Co-administration of morphine and O-1966 was tested under three dosing regimens: simultaneous administration, morphine pre-treated with O-1966, and O-1966 pre-treated with morphine. The effects of O-1966 on mu-opioid receptor binding were determined using [3H]DAMGO and [35S]GTPγS binding assays, and these interactions were further examined by FRET analysis linked to flow cytometry. Results yielded surprising evidence of interactions between the CB2 receptor selective agonist O-1966 and morphine that were dependent upon the order of administration. When O-1966 was administered prior to or simultaneous with morphine, morphine antinociception was attenuated and antinociceptive tolerance was exacerbated. When O-1966 was administered following morphine, morphine antinociception was not affected and antinociceptive tolerance was attenuated. The [35S]GTPγS results suggest that O-1966 interrupts functional activity of morphine at the mu-opioid receptor, leading to decreased potency of morphine to produce acute thermal antinociceptive effects and potentiation of morphine antinociceptive tolerance. However, O-1966 administered after morphine blocked morphine hyperalgesia and led to an attenuation of morphine tolerance, perhaps due to well-documented anti-inflammatory effects of CB2 receptor agonism.

Invasive scarab beetles, like the Japanese beetle Popillia japonica Newman (JB), spend most of their lives as larvae feeding in the soil matrix. Despite the potential importance of the larval gut microbial community in driving the behavior, physiology, and nutritional ecology of this invasive insect, the role of soil biological and physicochemical characteristics in shaping this community are relatively unknown. Our objectives were to (1) characterize the degree to which larval gut microbial communities are environmentally acquired, (2) examine the combined effects of the gut region (i.e., midgut, hindgut) and local soil environments on gut microbial communities, and (3) search for soil physicochemical correlates that could be useful in future studies aimed at characterizing gut microbial community variation in soil-dwelling scarabs. Gut communities from neonates that were never in contact with the soil were different from gut communities of third instar larvae collected from the field, with neonate gut communities being significantly less rich and diverse. The influence of compartment (soil, midgut, or hindgut) on prokaryotic α- and β-diversity varied with location, suggesting that JB larval gut communities are at least partially shaped by the local environment even though the influence of compartment was more pronounced. Midgut microbiota contained transient communities that varied with the surrounding soil environment whereas hindgut microbiota was more conserved. Prokaryotic communities in the hindgut clustered separately from those of soil and midgut, which displayed greater interspersion in ordination space. Soil cation exchange capacity, organic matter, water holding capacity, and texture were moderately correlated (≥29%) with gut prokaryotic microbial composition, especially within the midgut. Findings suggest that microbial communities associated with the JB gut are partially a function of adaptation to local soil environments. However, conditions within each gut compartment appear to shape those communities in transit through the alimentary canal.