julilili42/papers huggingface dataset:
Population‐based cohort imaging: skeletal muscle mass by magnetic resonance imaging in correlation to bioelectrical‐impedance analysis
2022-01-25

Abstract Background Skeletal muscle mass is subjected to constant changes and is considered a good predictor for outcome in various diseases. Bioelectrical‐impedance analysis (BIA) and magnetic resonance imaging (MRI) are approved methodologies for its assessment. However, muscle mass estimations by BIA may be influenced by excess intramuscular lipids and adipose tissue in obesity. The objective of this study was to evaluate the feasibility of quantitative assessment of skeletal muscle mass by MRI as compared with BIA. Methods Subjects from a population‐based cohort underwent BIA (50 kHz, 0.8 mA) and whole‐body MRI including chemical‐shift encoded MRI (six echo times). Abdominal muscle mass by MRI was quantified as total and fat‐free cross‐sectional area by a standardized manual segmentation‐algorithm and normalized to subjects' body height 2 (abdominal muscle mass indices: AMMI MRI ). Results Among 335 included subjects (56.3 ± 9.1 years, 56.1% male), 95 (28.4%) were obese (BMI ≥ 30 kg/m 2 ). MRI‐based and BIA‐based measures of muscle mass were strongly correlated, particularly in non‐obese subjects [ r &lt; 0.74 in non‐obese ( P &lt; 0.001) vs. r &lt; 0.56 in obese ( P &lt; 0.001)]. Median AMMI Total(MRI) was significantly higher in obese as compared with non‐obese subjects (3246.7 ± 606.1 mm 2 /m 2 vs. 2839.0 ± 535.8 mm 2 /m 2 , P &lt; 0.001, respectively), whereas the ratio AMMI Fat‐free /AMMI Total (by MRI) was significantly higher in non‐obese individuals (59.3 ± 10.1% vs. 53.5 ± 10.6%, P &lt; 0.001, respectively). No significant difference was found regarding AMMI Fat‐free(MRI) ( P = 0.424). In analyses adjusted for age and sex, impaired glucose tolerance and measures of obesity were significantly and positively associated with AMMI Total(MRI) and significantly and inversely with the ratio AMMI Fat‐free(MRI) /AMMI Total(MRI) ( P &lt; 0.001). Conclusions MRI‐based assessment of muscle mass is feasible in population‐based imaging and strongly correlated with BIA. However, the observed weaker correlation in obese subjects may explain the known limitation of BIA in obesity and promote MRI‐based assessments. Thus, skeletal muscle mass parameters by MRI may serve as practical imaging biomarkers independent of subjects' body weight.
Does body posture reduce the Stroop effect? Evidence from two conceptual replications and a meta-analysis
2022-01-25

Standing compared to sitting, for instance at work, is associated with positive physical and mental health consequences. Indeed, studies suggest that performance in cognitive conflict tasks (e.g., Color Stroop tasks) is improved when subjects perform the task while standing compared to sitting (Rosenbaum et al., 2018; Smith et al., 2019). However, a recent study failed to replicate these findings in five attempts (Caron et al., 2020). We aimed to shed light on these discrepant results by means of two conceptual replications and a meta-analysis. Replication experiments showed typical congruency effects in the Color Stroop task, but failed to find any influence of posture on the Stroop effect even when we subjected data to a more sensitive analysis that controlled for individual variances between participants. Additionally, an explorative Bayesian analysis confirmed that both replications provided strong evidence against an interaction between body posture and the Stroop effect. Meta-analytic results showed that the confidence interval of the overall effect size for a modulation of the Stroop effect by body posture includes the null. Together, our results question whether standing modulates the Stroop effect in Color Stroop tasks and points out limitations of the influence of body posture on cognitive control tasks.
The m6A writer FIONA1 methylates the 3’UTR of FLC and controls flowering in Arabidopsis
2022-01-25

ABSTRACT Adenosine bases of RNA can be transiently modified by the deposition of a methyl-group to form N 6 -methyladenosine (m 6 A). This adenosine-methylation is an ancient process and the enzymes involved are evolutionary highly conserved. A genetic screen designed to identified suppressors of late flowering transgenic Arabidopsis plants overexpressing the miP1a microProtein yielded a new allele of the FIONA1 (FIO1) m 6 A-methyltransferase. To characterize the early flowering phenotype of fio1 mutant plants we employed an integrative approach of mRNA-seq, Nanopore direct RNA-sequencing and meRIP-seq to identify differentially expressed transcripts as well as differentially methylated mRNAs. We provide evidence that FIO1 is the elusive methylase responsible for the 3’-end methylation of the FLOWERING LOCUS C ( FLC ) transcript. Furthermore, our genetic and biochemical data suggest that 3’-methylation stabilizes FLC mRNAs and non-methylated FLC is a target for rapid degradation.
The scotopic band: primate detailed scotopic vision and perceptual uncertainty
2022-01-25

Abstract Primates perceive detailed images in photopic (daylight) vision via a preferred-processing, high-acuity pathway, made up of a small photopic center (the fovea), and dedicated eye movements, whose function is to shift images of target objects to the fovea and keep them while foveal cones sense the image. Thus, the preferred processing pathway processes images serially, not in parallel. No such pathway is known for scotopic (night-light) vision or mesopic (twilight) vision – though details are informative in dim light, even vital; it remains unclear whether and how scotopic vision of details is accomplished. Here we show that primates do have a scotopic preferred-processing pathway. It consists of a ‘scotopic center’, located on a ‘scotopic band’, and eye movements that shift target images not to the fovea but directly to the scotopic center. In contrast to the stationary fovea, the scotopic center can relocate over the scotopic band. The scotopic center relocates to match changing visual conditions and contextual needs. Ambient light intensity is mapped monotonically onto the scotopic band, with mesopic vision at one end. The dimmer the light is, the more dorsal the scotopic center relocates on the scotopic band. Importantly, the scotopic center relocates (or ‘set’) not only in passive response to ambient light but also actively, driven by internal factors. In near-threshold conditions the scotopic center relocates to a more dorsal band location than in salient conditions. That the same relocation of the scotopic center can be instigated both by dimming the ambient light and by reducing the detectability of targets indicates that, at the core, the longitudinal axis of the scotopic band encodes the level of perceptual uncertainty.
Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer
2022-01-26

Significance Efforts to understand and find new treatment options for high-grade serous ovarian cancer (HGSOC) have been confounded by a paucity of immune-competent models that accurately reflect the genetics and biology of the disease. Here, we leverage somatic tissue engineering to develop a fast and flexible immune-competent mouse model of HGSOC and reveal mechanistic insights into factors that dictate the response of ovarian tumors to conventional chemotherapy and immune checkpoint blockade. Our results identify a genotype-dependent therapy-induced senescence program that mediates sensitivity and resistance to first line chemotherapy and point to strategies to harness the senescence program to sensitize ovarian tumors to immune checkpoint blockade.
Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials
2022-01-26

The potential of gossypol and of its R-(−)-enantiomer (R-(−)-gossypol acetic acid, AT-101), has been evaluated for treatment of cancer as an independent agent and in combination with standard chemo-radiation-therapies, respectively. This review assesses the evidence for safety and clinical effectiveness of oral gossypol/AT-101 in treating various types of cancer. The databases PubMed, MEDLINE, Cochrane, and ClinicalTrials.gov were examined. Phase I and II trials as well as single arm and randomized trials were included in this review. Results were screened to determine if they met inclusion criteria and then summarized using a narrative approach. A total of 17 trials involving 759 patients met the inclusion criteria. Overall, orally applied gossypol/AT-101 at low doses (30 mg daily or lower) was determined as well tolerable either as monotherapy or in combination with chemo-radiation. Adverse events should be strictly monitored and were successfully managed by dose-reduction or treating symptoms. There are four randomized trials, two performed in patients with advanced non-small cell lung cancer, one in subjects with head and neck cancer, and one in patients with metastatic castration-resistant prostate cancer. Thereby, standard chemotherapy (either docetaxel (two trials) or docetaxel plus cisplatin or docetaxel plus prednisone) was tested with and without AT-101. Within these trials, a potential benefit was observed in high-risk patients or in some patients with prolongation in progression-free survival or in overall survival. Strikingly, the most recent clinical trial combined low dose AT-101 with docetaxel, fluorouracil, and radiation, achieving complete responses in 11 of 13 patients with gastroesophageal carcinoma (median duration of 12 months) and a median progression-free survival of 52 months. The promising results shown in subsets of patients supports the need of further specification of AT-101 sensitive cancers as well as for the establishment of effective AT-101-based therapy. In addition, the lowest recommended dose of gossypol and its precise toxicity profile need to be confirmed in further studies. Randomized placebo-controlled trials should be performed to validate these data in large cohorts.
Mysterious odd radio circle near the large magellanic cloud – an intergalactic supernova remnant?
2022-01-26

ABSTRACT We report the discovery of J0624–6948, a low-surface brightness radio ring, lying between the Galactic Plane and the large magellanic cloud (LMC). It was first detected at 888 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP), and with a diameter of ∼196 arcsec. This source has phenomenological similarities to odd radio circles (ORCs). Significant differences to the known ORCs – a flatter radio spectral index, the lack of a prominent central galaxy as a possible host, and larger apparent size – suggest that J0624–6948 may be a different type of object. We argue that the most plausible explanation for J0624–6948 is an intergalactic supernova remnant due to a star that resided in the LMC outskirts that had undergone a single-degenerate type Ia supernova, and we are seeing its remnant expand into a rarefied, intergalactic environment. We also examine if a massive star or a white dwarf binary ejected from either galaxy could be the supernova progenitor. Finally, we consider several other hypotheses for the nature of the object, including the jets of an active galactic nucleus (30Dor) or the remnant of a nearby stellar super-flare.
Evolution of flexible biting in hyperdiverse parasitoid wasps
2022-01-26

One key event in insect evolution was the development of mandibles with two joints, which allowed powerful biting but restricted their movement to a single degree of freedom. These mandibles define the Dicondylia, which constitute over 99% of all extant insect species. It was common doctrine that the dicondylic articulation of chewing mandibles remained unaltered for more than 400 million years. We report highly modified mandibles overcoming the restrictions of a single degree of freedom and hypothesize their major role in insect diversification. These mandibles are defining features of parasitoid chalcid wasps, one of the most species-rich lineages of insects. The shift from powerful chewing to precise cutting likely facilitated adaptations to parasitize hosts hidden in hard substrates, which pose challenges to the emerging wasps. We reveal a crucial step in insect evolution and highlight the importance of comprehensive studies even of putatively well-known systems.
Juxtacellular opto-tagging of hippocampal CA1 neurons in freely moving mice
2022-01-26

Neural circuits are made of a vast diversity of neuronal cell types. While immense progress has been made in classifying neurons based on morphological, molecular, and functional properties, understanding how this heterogeneity contributes to brain function during natural behavior has remained largely unresolved. In the present study, we combined the juxtacellular recording and labeling technique with optogenetics in freely moving mice. This allowed us to selectively target molecularly defined cell classes for in vivo single-cell recordings and morphological analysis. We validated this strategy in the CA1 region of the mouse hippocampus by restricting Channelrhodopsin expression to Calbindin-positive neurons. Directly versus indirectly light-activated neurons could be readily distinguished based on the latencies of light-evoked spikes, with juxtacellular labeling and post hoc histological analysis providing ‘ground-truth’ validation. Using these opto-juxtacellular procedures in freely moving mice, we found that Calbindin-positive CA1 pyramidal cells were weakly spatially modulated and conveyed less spatial information than Calbindin-negative neurons – pointing to pyramidal cell identity as a key determinant for neuronal recruitment into the hippocampal spatial map. Thus, our method complements current in vivo techniques by enabling optogenetic-assisted structure–function analysis of single neurons recorded during natural, unrestrained behavior.
Pyridoxine or pyridoxal‐5‐phosphate treatment for seizures in glycosylphosphatidylinositol deficiency: A cohort study
2022-01-26

Aim To investigate the short‐term efficacy and safety of high‐dose pyridoxine and pyridoxal 5‐phosphate (P5P) in the treatment of inherited glycosylphosphatidylinositol (GPI) deficiency‐associated epilepsy. Method Participants with genetically confirmed GPI deficiency were treated with oral pyridoxine or P5P as compassionate use in an agreed‐upon clinical regimen. Pyridoxine (20–30 mg/kg/day) was used for 3 months. Baseline evaluation included 4 weeks of prospective seizure data and one video electroencephalogram (EEG). Seizure frequency was captured daily. The EEG was repeated after reaching maximum dosage of pyridoxine. Pyridoxine was switched to P5P (20–30 mg/kg/day) if seizure burden was unchanged after 3 months' treatment. Another EEG was done after 3 months of P5P treatment. Primary outcome measures were reduction of seizure frequency and EEG improvements. Results Seven participants (one female, six males; age range 5–23 year; mean age 11 years 10 months, SD 5 year 2 months) were included. The genetic causes of inherited GPI deficiency were phosphatidylinositol N‐acetylglucosaminyltransferase subunit A/T/V deficiency. All had drug‐resistant epilepsy and neurodevelopmental impairment. We observed more than 50% seizure frequency reduction in 2 out of 7 and less than 50% reduction in another 3 out of 7 participants. No participants reached seizure freedom. No remarkable changes in electrophysiological findings were observed in 6 out of 7 participants treated with pyridoxine or P5P when comparing the baseline and follow‐up EEGs. Interpretation We observed no long‐lasting electrophysiological improvements during treatment but pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency. What this paper adds Inherited glycosylphosphatidylinositol (GPI) deficiency often causes early‐onset and drug‐resistant epilepsy. Vitamin B 6 is a potential disease‐specific treatment; however, efficacy and safety are ill‐defined. Pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency. Pyridoxine and P5P could prove to be a useful treatment in some individuals with inherited GPI deficiency and epilepsy.
Fully Automated Artery-Specific Calcium Scoring Based on Machine Learning in Low-Dose Computed Tomography Screening
2022-01-26

Purpose Evaluation of machine learning-based fully automated artery-specific coronary artery calcium (CAC) scoring software, using semi-automated software as a reference. Methods A total of 505 patients underwent non-contrast-enhanced calcium scoring computed tomography (CSCT). Automated, machine learning-based software quantified the Agatston score (AS), volume score (VS), and mass score (MS) of each coronary artery [right coronary artery (RCA), left main (LM), circumflex (CX) and left anterior descending (LAD)]. Identified CAC of readers who annotated the data with semi-automated software served as a reference standard. Statistics included comparisons of evaluation time, agreement of identified CAC, and comparisons of the AS, VS, and MS of the reference standard and the fully automated algorithm. Results The machine learning-based software correlated strongly with the reference standard for the AS, VS, and MS (Spearmanʼs rho &gt; 0.969) (p &lt; 0.001), with excellent agreement (ICC &gt; 0.919) (p &lt; 0.001). The mean assessment time of the reference standard was 59 seconds (IQR 39–140) and that of the automated algorithm was 5.9 seconds (IQR 3.9–16) (p &lt; 0.001). The Bland-Altman plots mean difference and 1.96 upper and lower limits of agreement for all arteries combined were: AS 0.996 (1.33 to 0.74), VS 0.995 (1.40 to 0.71), and MS 0.995 (1.35 to 0.74). The mean bias was minimal: 0.964–1.0429. Risk class assignment showed high accuracy for the AS in total (weighed κ = 0.99) and for each individual artery (κ = 0.96–0.99) with corresponding correct risk group assignment in 497 of 505 patients (98.4 %). Conclusion The fully automated artery-specific coronary calcium scoring algorithm is a time-saving procedure and shows excellent correlation and agreement compared with the clinically established semi-automated approach. Key points: Citation Format
Serum creatinine baseline fluctuation and acute kidney injury after intravenous or intra-arterial contrast agent administration—an intraindividual comparison as part of a randomized controlled trial
2022-01-26

Contrast agents are widely used for imaging procedures and thus adverse reactions have wide-ranging consequences [1, 2]. However, there is mounting evidence that the contrast agent itself, especially when administered intravenously (IV), plays a limited role in the development of acute kidney injury (AKI) [3]. In case of intraarterial (IA) administration, the observed association with atheroembolism might result from catherization and not the contrast agent. While several studies suggest that the rate of contrast-agent-associated AKI is overestimated [4–7], determining the actual rate of AKI that is attributable to contrast agent administration would require randomizing patients to contrast- or non-contrast imaging, which is ethically not feasible [2]. Nonrandomized studies found no difference in AKI between patients who underwent non-contrast computed tomography (CT) versus contrast-enhanced CT [4, 6, 8, 9]. Because of the lack of control groups in...
People With Parkinson’s Disease and Freezing of Gait Show Abnormal Low Frequency Activity of Antagonistic Leg Muscles
2022-01-26

Objective Freezing of gait is detrimental to patients with idiopathic Parkinson’s disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity. Methods We analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBS only) or the substantia nigra pars reticulate (SNr-DBS only ), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in ‘regular gait’ and during the ‘freezing’ episodes. Results In stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing. Conclusion We found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator.
Hybrid Representations for Composition Optimization and Parallelizing MOEAs
2022-01-26

We present a hybrid EA representation suitable to optimize composition optimization problems ranging from optimizing recipes for catalytic materials to cardinality constrained portfolio selection. On several problem instances we can show that this new representation performs better than standard repair mechanisms with Lamarckism. Additionally, we investigate the a clustering based parallelization scheme for MOEAs. We prove that typical "divide and conquer'' approaches are not suitable for the standard test functions like ZDT 1-6. Therefore, we suggest a new test function based on the portfolio selection problem and prove the feasibility of "divide and conquer'' approaches on this test function.
SepN is essential for assembly and gating of septal junctions in Nostoc sp. PCC 7120
2022-01-26

Summary The multicellular life style of filamentous cyanobacteria like Nostoc sp. PCC7120 relies on a cell-cell communication system involving so called septal junctions. These are multiprotein complexes, which traverse the septal peptidoglycan through nanopores, connecting the neighboring cells and enabling molecule transfer along the filament. The intercellular communication is crucial when different cell types in the filament, vegetative cells and heterocysts, have to exchange metabolites and signaling molecules. Septal junctions of cyanobacteria can even control the molecule exchange by gating. The multiprotein complex consists of three modules: the septum spanning tube, the plug residing within the cytoplasmic membrane at both ends of the tube and a membrane associated cap module, covering the plug/tube modules on the cytoplasmic side of each neighboring cell. Until now, FraD was the only identified protein component of the septal junction protein complexes and localizes to the plug module. Here, we identified SepN as a new component via co-immunoprecipitation using FraD as bait and further demonstrated its essential role in septal junction assembly. Despite normal septal nanopore formation, a mutant in sepN exhibited a highly reduced rate of intercellular communication and was unable to gate the exchange of molecules. Cryo-electron tomography of cryo-focused ion beam thinned sepN -mutant filaments revealed septal junctions lacking the plug module and lateral cap openings. The combination of missing plug but present cap allowed to deduce the importance of the plug module in ensuring the correct cap architecture and, more importantly, in sealing the diffusion area in the closed septal junction state.