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Amyotrophic lateral sclerosis (ALS) primarily affects motor and speech abilities. In addition, cognitive functions are impaired in a subset of patients. There is a need to establish an eye movement-based method of neuropsychological assessment suitable for severely physically impaired patients with ALS. Forty-eight ALS patients and thirty-two healthy controls matched for age, sex and education performed a hand and speech motor-free version of the Raven’s coloured progressive matrices (CPM) and the D2-test which had been especially adapted for eye-tracking control. Data were compared to a classical motor-dependent paper–pencil version. The association of parameters of the eye-tracking and the paper–pencil version of the tests and the differences between and within groups were studied. Subjects presented similar results in the eye-tracking and the corresponding paper–pencil versions of the CPM and D2-test: a correlation between performance accuracy for the CPM was observed for ALS patients ( p  < 0.001) and controls ( p  < 0.001) and in the D2-test for controls ( p  = 0.048), whereas this correlation did not reach statistical significance for ALS patients ( p  = 0.096). ALS patients performed worse in the CPM than controls in the eye-tracking ( p  = 0.053) and the paper–pencil version ( p  = 0.042). Most importantly, eye-tracking versions of the CPM ( p  < 0.001) and the D2-test ( p  = 0.024) reliably distinguished between more and less cognitively impaired patients. Eye-tracking-based neuropsychological testing is a promising approach for assessing cognitive deficits in patients who are unable to speak or write such as patients with severe ALS.

COVID-19 is associated with cardiac dysfunction. This study tested the relative prognostic role of left (LV), right and bi- (BiV) ventricular dysfunction on mortality in a large multicenter cohort of patients during and after acute COVID-19 hospitalization. All hospitalized COVID-19 patients who underwent clinically indicated transthoracic echocardiography within 30 days of admission at four NYC hospitals between March 2020 and January 2021 were studied. Images were re-analyzed by a central core lab blinded to clinical data. Nine hundred patients were studied (28% Hispanic, 16% African-American), and LV, RV and BiV dysfunction were observed in 50%, 38% and 17%, respectively. Within the overall cohort, 194 patients had TTEs prior to COVID-19 diagnosis, among whom LV, RV, BiV dysfunction prevalence increased following acute infection (p<0.001). Cardiac dysfunction was linked to biomarker-evidenced myocardial injury, with higher prevalence of troponin elevation in patients with LV (14%), RV (16%) and BiV (21%) dysfunction compared to those with normal BiV function (8%, all p<0.05). During in- and out-patient follow-up, 290 patients died (32%), among whom 230 died in the hospital and 60 post-discharge. Unadjusted mortality risk was greatest among patients with BiV (41%), followed by RV (39%) and LV dysfunction (37%), compared to patients without dysfunction (27%, all p<0.01). In multivariable analysis, any RV dysfunction, but not LV dysfunction, was independently associated with increased mortality risk (p<0.01). LV, RV and BiV function declines during acute COVID-19 infection with each contributing to increased in- and out-patient mortality risk. RV dysfunction independently increases mortality risk.

Plant-based food-webs (‘green food-webs’) have historically been articulated as distinct from detritus-based food-webs (‘brown food-webs’). It has proven difficult to integrate these two spheres using a shared metric because of the difficulties in identifying and quantifying biodiversity within the microbiome. As a result, the trophic ecology of brown food-webs is much less well-understood than that of their green counterparts. Here we characterise the trophic niches of microorganisms by testing how animals and microbes assimilate stable isotopes within specific amino acids. Amino acid isotopic ‘fingerprinting’ provides unprecedented accuracy in the estimation of animal trophic tendency. Using this approach, we measured the isotopic signatures of amino acids extracted from a diversity of fungal species, as well as from crustaceans, fish, insects, and mammals (taxa representing the vast majority of global fauna). Fungal and animal taxa were trophically indistinguishable from one another when fed the same diet. Thus, despite profound phylogenetic disparities, these consumers exhibited similar patterns of isotopic fractionation and were trophically interchangeable, allowing fungi and animals to be interdigitated within food-webs. We brought this approach to bear upon the fungus-gardens of tropical leaf-cutter ants (Acromyrmex), revealing four discrete trophic levels within the fungus-gardens. Our data suggest that leaf-cutter ants are not the dominant herbivores of the Neotropics; rather, it is the fungi they cultivate. Further, the bacteria used by the ants as anti-fungal agents were shown to feed exclusively on the ants, indicating a tightly linked ant-bacterial mutualism. Because amino acid isotopic analysis quantifies trophic position independent of phylogeny, it facilitates unambiguous measurement of trophic function across biological kingdoms, effectively uniting ‘green’ and ‘brown’ food-webs.

Many monogenic disorders cause a characteristic facial morphology. Artificial intelligence can support physicians in recognizing these patterns by associating facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this ‘supervised’ approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we developed GestaltMatcher, an encoder for portraits that is based on a deep convolutional neural network. Photographs of 17,560 patients with 1,115 rare disorders were used to define a Clinical Face Phenotype Space, in which distances between cases define syndromic similarity. Here we show that patients can be matched to others with the same molecular diagnosis even when the disorder was not included in the training set. Together with mutation data, GestaltMatcher could not only accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism but also enable the delineation of new phenotypes. GestaltMatcher uses a deep convolutional neural network to improve recognition of rare disorders based on facial morphology. The framework detects similarities among patients with previously unseen syndromes, aiding discovery of new disease genes.

Circulating tumor cells (CTCs) play an important role in metastasis formation. Aberrant signaling of oncogenic pathways (e.g., PI3K/AKT/mTOR pathway) drives tumor progression. In this work, the susceptibility of the colon cancer CTC‐derived cell line CTC‐MCC‐41 to AKT and mammalian target of rapamycin (mTOR) inhibitors was evaluated. Additionally, the functional role of the expressed AKT isoforms was characterized in this cell line. The efficacy of the AKT inhibitor MK2206, the mTOR inhibitor RAD001, and the combination was examined in CTC‐MCC‐41 cells in a murine intracardiac xenotransplantation model. Furthermore, stable isoform‐specific AKT1 or AKT2 knockdowns (KDs) as well as AKT1/AKT2 double‐KD cells were generated. Differentially regulated proteins and phospho‐peptides were identified using liquid chromatography coupled mass spectrometry (LC–MS). CTC‐MCC‐41 cells showed a high susceptibility for dual targeting of AKT and mTOR in vivo, indicating that selective eradication of CTCs by AKT/mTOR inhibitors may be considered a new treatment option in cancer. KD of AKT1 or AKT2 significantly reduced the proliferation of CTC‐MCC‐41 cells. AKT KDs share commonly regulated proteins and phospho‐proteins, but also regulate a large number uniquely. AKT1/AKT2 double‐KD cells show a strongly dysregulated replication machinery, as well as a decrease in cell cycle activity and stem‐cell‐associated processes, underlining the non‐redundant role of AKT isoforms. Dual targeting of AKT and mTOR using MK2206 and RAD001 reduces tumor burden in an intracardiac colon cancer circulating tumor cell xenotransplantation model. Analysis of AKT isoform‐specific knockdowns in CTC‐MCC‐41 reveals differentially regulated proteins and phospho‐proteins by liquid chromatography coupled mass spectrometry.

Tics are unique from most movement disorders, in that they are partially suppressible. As part of the inhibitory motor network, the pre-supplementary motor area is engaged in motor control and may be involved in tic physiology. We used dual-site transcranial magnetic stimulation to assess inhibitory connectivity between right pre-supplementary motor area and left primary motor cortex, which has previously been demonstrated in healthy adults. We also used diffusion tensor imaging to investigate white matter connectivity in children with chronic tics. Twelve children with chronic tic disorder and fourteen typically developing controls underwent MRI with diffusion tensor imaging indices analysis followed by single and paired-pulse transcranial magnetic stimulation with conditioning pulse over the right pre-supplementary motor area followed by left motor cortex test pulse. Neurophysiologic and imaging data relationships to measures of tic severity and suppressibility were also evaluated in tic patients. Pre-supplementary motor area-mediated inhibition of left motor cortex was present in healthy control children but not in chronic tic disorder participants. Less inhibition correlated with worse tic suppressibility (ρ = − 0.73, p = 0.047). Imaging analysis showed increased fractional anisotropy in the right superior longitudinal fasciculus, corpus callosum, corona radiata and posterior limb of the internal capsule (p < 0.05) in tic participants, which correlated with lower self-reported tic suppressibility (ρ = − 0.70, p = 0.05). Physiologic data revealed impaired frontal-mediated motor cortex inhibition in chronic tic participants, and imaging analysis showed abnormalities in motor pathways. Collectively, the neurophysiologic and neuroanatomic data correlate with tic suppressibility, supporting the relevancy to tic pathophysiology.

Background The “Positive Action for Today’s Health” (PATH) trial tested an environmental intervention to increase walking in underserved communities. Methods Three matched communities were randomized to a police-patrolled walking plus social marketing, a police-patrolled walking-only, or a no-walking intervention. The 24-month intervention addressed safety and access for physical activity (PA) and utilized social marketing to enhance environmental supports for PA. African-Americans ( N  = 434; 62 % females; aged 51 ± 16 years) provided accelerometry and psychosocial measures at baseline and 12, 18, and 24 months. Walking attendance and trail use were obtained over 24 months. Results There were no significant differences across communities over 24 months for moderate-to-vigorous PA. Walking attendance in the social marketing community showed an increase from 40 to 400 walkers per month at 9 months and sustained ~200 walkers per month through 24 months. No change in attendance was observed in the walking-only community. Conclusions Findings support integrating social marketing strategies to increase walking in underserved African-Americans (ClinicalTrials.gov #NCT01025726).

Popular methods for analyzing accelerometer data often use a single physical activity outcome variable such as average-weekly or total physical activity. These approaches limit the types of research questions that can be answered and fail to utilize the detailed, time-specific information available from accelerometers. This study proposes the use of multilevel modeling, which tested intervention effects at specific time periods. The motivating example was the Active by Choice Today trial. Simulations were used to test whether the application of time-specific hypotheses about when physical activity intervention treatment effects were expected to occur (e.g., after-school hours) increased power to detect effects compared to traditional methods. Six simulation conditions were tested: (1) no treatment effects (to test the type 1 error rate), (2) time-specific effects, but no traditionally-tested effects, (3) traditionally-tested effects, but no time-specific effects, and (4) combinations of traditional and time-specific effects in 3 proportions. Results showed the proposed multilevel approach demonstrated appropriate type 1 error rates and increased power to detect treatment effects during hypothesized times by 31–38 percentage points compared to traditional approaches. This was consistent across varying proportions of traditional versus time-specific effects, and there was no loss of power using the multilevel approach when only traditional effects were present. The current study showed potential advantages of testing time-specific hypotheses about intervention effects using a multilevel time-specific approach. This approach may show intervention effects when traditional approaches do not. Future research should explore the application of this additional analytic tool for accelerometer physical activity estimates.

The livestock industry negatively impacts the environment by producing high organic and mineral loaded manure and wastewater. On the contrary, manure is also considered as the major focal point of resource recovery. The microfiltration (MF) process in manure treatment is well known for being the least complex and highly energy efficient. However, the major fraction of the dissolve nutrients easily bypasses the MF membranes. In this research work, we reported the efficiency of using MF–nanofiltration (NF) treatment train in a dead-end filtration system for the treatment of raw manure. The objectives were to produce nutrient rich separate streams in reduced volumes and a particle and pathogen-free product water. MF removed TSS above 98% and the COD and phosphorus (P) retention were noticed above 60 and 80%, respectively, within a reduced MF concentrate volume, which accounted for 40% of the initial feed volume. The NF of MF permeate by NF270 showed most promising results by concentrating overall 50 and 70% of the total nitrogen (TN) and potassium (K) within a reduced NF concentrate volume, which accounted for 30% of the initial MF feed volume. Finally, the MF–NF treatment train of raw pig manure could produce a particle-free product water that can be reused in farms to wash barns, to irrigate nearby cultures, or can be applied to specific fields based on the demand.