bluuebunny/crossref_metadata_2025 huggingface dataset:
The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury
Authors: Ning Li , Rui Xiong , Bo Wang , Qing Geng
Published: July 2021

Histone deacetylase 3 (HDAC3) plays a crucial role in chromatin remodeling, which, in turn, regulates gene transcription. Hence, HDAC3 has been implicated in various diseases, including ischemic injury, fibrosis, neurodegeneration, infections, and inflammatory conditions. In addition, HDAC3 plays vital roles under physiological conditions by regulating circadian rhythms, metabolism, and development. In this review, we summarize the current knowledge of the physiological functions of HDAC3 and its role in organ injury. We also discuss the therapeutic value of HDAC3 in various diseases.
Identification of a prognostic ferroptosis-related lncRNA signature in the tumor microenvironment of lung adenocarcinoma
Authors: Guo Yugang , Qu Zhongyu , Li Dandan , Bai Fanghui , Xing Juan , Ding Qian , Zhou Jiawei , Yao Lunguang , Xu Qian
Published: July 2021

Ferroptosis is closely linked to various cancers, including lung adenocarcinoma (LUAD); however, the factors involved in the regulation of ferroptosis-related genes are not well established. In this study, we identified and characterized ferroptosis-related long noncoding RNAs (lncRNAs) in LUAD. In particular, a coexpression network of ferroptosis-related mRNAs and lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic ferroptosis-related lncRNA signature (FerRLSig). We obtained a prognostic risk model consisting of 10 ferroptosis-related lncRNAs: AL606489.1, AC106047.1, LINC02081, AC090559.1, AC026355.1, FAM83A-AS1, AL034397.3, AC092171.5, AC010980.2, and AC123595.1. High risk scores according to the FerRLSig were significantly associated with poor overall survival (hazard ratio (HR) = 1.412, 95% CI = 1.271–1.568; P < 0.001). Receiver operating characteristic (ROC) curves and a principal component analysis further supported the accuracy of the model. Next, a prognostic nomogram combining FerRLSig with clinical features was established and showed favorable predictive efficacy for survival risk stratification. In addition, gene set enrichment analysis (GSEA) revealed that FerRLSig is involved in many malignancy-associated immunoregulatory pathways. Based on the risk model, we found that the immune status and response to immunotherapy, chemotherapy, and targeted therapy differed significantly between the high-risk and low-risk groups. These results offer novel insights into the pathogenesis of LUAD, including the contribution of ferroptosis-related lncRNAs, and reveal a prognostic indicator with the potential to inform immunological research and treatment.
Quantitative imaging of transcription in living Drosophila embryos reveals the impact of core promoter motifs on promoter state dynamics
Authors: Pimmett Virginia L. , Dejean Matthieu , Fernandez Carola , Trullo Antonio , Bertrand Edouard , Radulescu Ovidiu , Lagha Mounia
Published: July 2021

Genes are expressed in stochastic transcriptional bursts linked to alternating active and inactive promoter states. A major challenge in transcription is understanding how promoter composition dictates bursting, particularly in multicellular organisms. We investigate two key Drosophila developmental promoter motifs, the TATA box (TATA) and the Initiator (INR). Using live imaging in Drosophila embryos and new computational methods, we demonstrate that bursting occurs on multiple timescales ranging from seconds to minutes. TATA-containing promoters and INR-containing promoters exhibit distinct dynamics, with one or two separate rate-limiting steps respectively. A TATA box is associated with long active states, high rates of polymerase initiation, and short-lived, infrequent inactive states. In contrast, the INR motif leads to two inactive states, one of which relates to promoter-proximal polymerase pausing. Surprisingly, the model suggests pausing is not obligatory, but occurs stochastically for a subset of polymerases. Overall, our results provide a rationale for promoter switching during zygotic genome activation.
Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks
Authors: Karapinar Raziye , Schwitalla Jan Claudius , Eickelbeck Dennis , Pakusch Johanna , Mücher Brix , Grömmke Michelle , Surdin Tatjana , Knöpfel Thomas , Mark Melanie D. , Siveke Ida , Herlitze Stefan
Published: July 2021

Opn7b is a non-visual G protein-coupled receptor expressed in zebrafish. Here we find that Opn7b expressed in HEK cells constitutively activates the Gi/o pathway and illumination with blue/green light inactivates G protein-coupled inwardly rectifying potassium channels. This suggests that light acts as an inverse agonist for Opn7b and can be used as an optogenetic tool to inhibit neuronal networks in the dark and interrupt constitutive inhibition in the light. Consistent with this prediction, illumination of recombinant expressed Opn7b in cortical pyramidal cells results in increased neuronal activity. In awake mice, light stimulation of Opn7b expressed in pyramidal cells of somatosensory cortex reliably induces generalized epileptiform activity within a short (<10 s) delay after onset of stimulation. Our study demonstrates a reversed mechanism for G protein-coupled receptor control and Opn7b as a tool for controlling neural circuit properties.
Past and future trends of Egypt’s water consumption and its sources
Authors: Nikiel Catherine A. , Eltahir Elfatih A. B.
Published: July 2021

For millennia the Nile supplied Egypt with more water than needed. As the population grew and the economy expanded, demand on water increased accordingly. Here, we present a comprehensive analysis to reconstruct how total demand on water outstripped supply of the Nile water in the late 1970s, starting from a surplus of about 20 km3 per year in the 1960s leading to a deficit of about 40 km3 per year by the late 2010s. The gap is satisfied by import of virtual water. The role of economic growth in driving per capita demand on water is quantified based on detailed analysis of water use by agriculture and other sectors. We develop and test an empirical model of water demand in Egypt that relates demand on water to growth rates in the economy and population. Looking forward, we project that within this decade of the 2020 s, under nominal scenarios of population and economic growth, Egypt is likely to import more virtual water than the water supplied by the Nile, bringing into question the historical characterization of Egypt as “the gift of the Nile”.
Auditory input enhances somatosensory encoding and tactile goal-directed behavior
Authors: Godenzini L. , Alwis D. , Guzulaitis R. , Honnuraiah S. , Stuart G. J. , Palmer L. M.
Published: July 2021

The capacity of the brain to encode multiple types of sensory input is key to survival. Yet, how neurons integrate information from multiple sensory pathways and to what extent this influences behavior is largely unknown. Using two-photon Ca2+ imaging, optogenetics and electrophysiology in vivo and in vitro, we report the influence of auditory input on sensory encoding in the somatosensory cortex and show its impact on goal-directed behavior. Monosynaptic input from the auditory cortex enhanced dendritic and somatic encoding of tactile stimulation in layer 2/3 (L2/3), but not layer 5 (L5), pyramidal neurons in forepaw somatosensory cortex (S1). During a tactile-based goal-directed task, auditory input increased dendritic activity and reduced reaction time, which was abolished by photoinhibition of auditory cortex projections to forepaw S1. Taken together, these results indicate that dendrites of L2/3 pyramidal neurons encode multisensory information, leading to enhanced neuronal output and reduced response latency during goal-directed behavior.
Deacetylation as a receptor-regulated direct activation switch for pannexin channels
Authors: Chiu Yu-Hsin , Medina Christopher B. , Doyle Catherine A. , Zhou Ming , Narahari Adishesh K. , Sandilos Joanna K. , Gonye Elizabeth C. , Gao Hong-Yu , Guo Shih Yi , Parlak Mahmut , Lorenz Ulrike M. , Conrads Thomas P. , Desai Bimal N. , Ravichandran Kodi S. , Bayliss Douglas A.
Published: July 2021

Activation of Pannexin 1 (PANX1) ion channels causes release of intercellular signaling molecules in a variety of (patho)physiological contexts. PANX1 can be activated by G protein-coupled receptors (GPCRs), including α1-adrenergic receptors (α1-ARs), but how receptor engagement leads to channel opening remains unclear. Here, we show that GPCR-mediated PANX1 activation can occur via channel deacetylation. We find that α1-AR-mediated activation of PANX1 channels requires Gαq but is independent of phospholipase C or intracellular calcium. Instead, α1-AR-mediated PANX1 activation involves RhoA, mammalian diaphanous (mDia)-related formin, and a cytosolic lysine deacetylase activated by mDia – histone deacetylase 6. HDAC6 associates with PANX1 and activates PANX1 channels, even in excised membrane patches, suggesting direct deacetylation of PANX1. Substitution of basally-acetylated intracellular lysine residues identified on PANX1 by mass spectrometry either prevents HDAC6-mediated activation (K140/409Q) or renders the channels constitutively active (K140R). These data define a non-canonical RhoA-mDia-HDAC6 signaling pathway for GαqPCR activation of PANX1 channels and uncover lysine acetylation-deacetylation as an ion channel silencing-activation mechanism.
Update on the effects of microgravity on the musculoskeletal system
Authors: Juhl Otto J. , Buettmann Evan G. , Friedman Michael A. , DeNapoli Rachel C. , Hoppock Gabriel A. , Donahue Henry J.
Published: July 2021

With the reignited push for manned spaceflight and the development of companies focused on commercializing spaceflight, increased human ventures into space are inevitable. However, this venture would not be without risk. The lower gravitational force, known as microgravity, that would be experienced during spaceflight significantly disrupts many physiological systems. One of the most notably affected systems is the musculoskeletal system, where exposure to microgravity causes both bone and skeletal muscle loss, both of which have significant clinical implications. In this review, we focus on recent advancements in our understanding of how exposure to microgravity affects the musculoskeletal system. We will focus on the catabolic effects microgravity exposure has on both bone and skeletal muscle cells, as well as their respective progenitor stem cells. Additionally, we report on the mechanisms that underlie bone and muscle tissue loss resulting from exposure to microgravity and then discuss current countermeasures being evaluated. We reveal the gaps in the current knowledge and expound upon how current research is filling these gaps while also identifying new avenues of study as we continue to pursue manned spaceflight.
Phenethylamine in chlorella alleviates high-fat diet-induced mouse liver damage by regulating generation of methylglyoxal
Authors: Zheng Yifeng , Martin-Morales Agustin , Wang Jing , Fujishima Masaki , Okumura Eri , Sato Kenji
Published: July 2021

This study examined the effects of oral administration of water extract of chlorella (WEC) (100 mg/kg bodyweight) and phenethylamine (10 μg/kg bodyweight) on high-fat diet (HFD)-induced liver damage in mice. Phenethylamine significantly mitigated HFD-induced lipid oxidation (generation of malondialdehyde) and liver damage without markedly decreasing hepatic lipid accumulation. WEC exerted similar effects although with decreased efficacy. In addition, WEC and phenethylamine decreased the methylglyoxal levels and increased the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein levels in the liver. Methylglyoxal is generated from substrates of GAPDH, dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. These facts indicate that methylglyoxal triggers oxidation of accumulated lipid, which generates malondialdehyde and consequently induces liver damage. Suppression of generation of toxic aldehydes by WEC and phenethylamine was also confirmed by maintaining hepatic cysteine, highly reactive to aldehydes. Thus, trace amounts of phenethylamine alleviate HFD-induced liver damage by regulating methylglyoxal via increase of GAPDH.
A large-scale multi-institutional study evaluating prognostic aspects of positive ascites cytology and effects of therapeutic interventions in epithelial ovarian cancer
Authors: Yoshihara Masato , Emoto Ryo , Kitami Kazuhisa , Iyoshi Shohei , Uno Kaname , Mogi Kazumasa , Tano Sho , Yoshikawa Nobuhisa , Matsui Shigeyuki , Kajiyama Hiroaki
Published: July 2021

Positive ascites cytology is a strong prognostic factor in patients with early-stage ovarian cancer (OvCa). However, limited information is currently available on the impact of positive ascites cytology on patient prognoses under each clinical background. We herein investigated the comprehensive impact of positive ascites cytology on patients with epithelial OvCa and the effectiveness of additional therapeutic interventions, including complete staging surgery and chemotherapy. Among 4730 patients with malignant ovarian neoplasms, retrospectively identified in multiple institutions, 1906 with epithelial OvCa were included. In the investigation of its effects on clinical factors using a multivariate analysis, positive ascites cytology correlated with a poor prognosis. Positive ascites cytology had a significantly worse prognosis than those with negative cytology in all subgroups except for patients with stage IV tumors and a mucinous histology. Chemotherapy may be effective in reducing the negative impact of positive ascites cytology on the prognosis of patients in terms of progression-free and overall survivals, while complete staging surgery did not improve the prognosis of patients with positive ascites cytology. Collectively, our findings suggested that positive ascites cytology had a negative impact on the prognosis of patients with epithelial OvCa, but not those with stage IV tumors or a mucinous histology.
A new strategy to uncover fragile X proteomic biomarkers using the nascent proteome of peripheral blood mononuclear cells (PBMCs)
Authors: Dionne Olivier , Corbin François
Published: July 2021

Fragile X syndrome (FXS) is the most prevalent inherited cause of intellectual disabilities and autism spectrum disorders. FXS result from the loss of expression of the FMRP protein, an RNA-binding protein that regulates the expression of key synaptic effectors. FXS is also characterized by a wide array of behavioural, cognitive and metabolic impairments. The severity and penetrance of those comorbidities are extremely variable, meaning that a considerable phenotypic heterogeneity is found among fragile X individuals. Unfortunately, clinicians currently have no tools at their disposal to assay a patient prognosis upon diagnosis. Since the absence of FMRP was repeatedly associated with an aberrant protein synthesis, we decided to study the nascent proteome in order to screen for potential proteomic biomarkers of FXS. We used a BONCAT (Biorthogonal Non-canonical Amino Acids Tagging) method coupled to label-free mass spectrometry to purify and quantify nascent proteins of peripheral blood mononuclear cells (PBMCs) from 7 fragile X male patients and 7 age-matched controls. The proteomic analysis identified several proteins which were either up or downregulated in PBMCs from FXS individuals. Eleven of those proteins were considered as potential biomarkers, of which 5 were further validated by Western blot. The gene ontology enrichment analysis highlighted molecular pathways that may contribute to FXS physiopathology. Our results suggest that the nascent proteome of PBMCs is well suited for the discovery of FXS biomarkers.
Novel CuO/Mn3O4/ZnO nanocomposite with superior photocatalytic activity for removal of Rabeprazole from water
Authors: Raha Sauvik , Mohanta Dipyaman , Ahmaruzzaman Md.
Published: July 2021

In this work, a nanohybrid of CuO/Mn3O4/ZnO was generated through a simple hydrothermal based procedure. The CuO/Mn3O4/ZnO nanohybrid has been characterized using X-ray diffraction, transmission electron microscopy high resolution transmission electron microscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and energy dispersive X-ray analysis. UV–visible spectrophotometry and photoluminescence techniques allowed evaluation of optical properties that additionally suggested the prevalence of strong interfacial interaction between the three moieties of the nanohybrid and suppressed electron–hole recombination. The hybrid photocatalyst brought on ~ 97.02 ± 1.15% disintegration of rabeprazole when illuminated with visible light. The progress of the photodegradation was in conformity with pseudo-first order kinetic model and had a velocity constant of 0.07773 min−1. Additionally, ~ 84.45% of total organic carbon removal was achieved while chemical oxygen demand was reduced by ~ 73.01%. Using high resolution liquid chromatograph mass spectrometry technique, identification of the degraded products was made and accordingly the mechanistic route of the aforesaid degradation was proposed.
Defect localization by an extended laser source on a hemisphere
Authors: Veira Canle Daniel , Mäkinen Joni , Blomqvist Richard , Gritsevich Maria , Salmi Ari , Hæggström Edward
Published: July 2021

The primary goal of this study is to localize a defect (cavity) in a curved geometry. Curved topologies exhibit multiple resonances and the presence of hotspots for acoustic waves. Launching acoustic waves along a specific direction e.g. by means of an extended laser source reduces the complexity of the scattering problem. We performed experiments to demonstrate the use of a laser line source and verified the experimental results in FEM simulations. In both cases, we could locate and determine the size of a pit in a steel hemisphere which allowed us to visualize the defect on a 3D model of the sample. Such an approach could benefit patients by enabling contactless inspection of acetabular cups.
Correlation between gastroesophageal flap valve abnormality and novel parameters in patients with gastroesophageal reflux disease symptoms by the lyon consensus
Authors: Guo Zihao , Wu Yanhong , Zhan Yutao , Zhang Chuan
Published: July 2021

Gastroesophageal flap valve (GEFV) grading is a simple and reproducible parameter. There is limited information about the association between GEFV abnormality and novel parameters in patients with gastroesophageal reflux disease(GERD) symptoms by the Lyon Consensus. To investigate the value of GEFV grading in GERD, the clinical data of 320 patients with GERD symptoms who underwent endoscopy, 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, and high-resolution manometry (HRM) were retrospectively analyzed. The percentage of acid exposure time (AET%)(4.2 [1.5–7.4] vs. 1.3 [0.3–4.2], P < 0.001) and the proportion of abnormal esophagogastric junction (EGJ) morphology (71 [87.7%] vs. 172 [72.0%], P = 0.011) were significantly higher, while the mean nocturnal baseline impedance (MNBI) (2068.3 [1658.4–2432.4] vs. 2228.5 [1794.8–2705.3]Ω, P = 0.012) and post-reflux swallow-induced peristaltic wave index (PSPWI) (19.7 [13.9–29.0] vs. 33.3 [25.0–44.0]%, P < 0.001) were significantly lower in the abnormal GEFV group compared with the normal GEFV group. AET% and EGJ morphology showed positive correlations with GEFV grade, while PSPWI and MNBI showed negative correlations. Patients with an abnormal GEFV had a significantly greater risk of conclusive evidence of GERD compared to those with a normal GEFV (OR 3.035, 95% CI 1.758–5.240, P < 0.001). Further, when identifying patients with conclusive evidence of GERD, abnormal GEFV had a specificity of 80.4% (95% CI 75.3–85.5%). GEFV grading might be regarded as supportive evidence for GERD diagnosis.
Niche partitioning among dead wood-dependent beetles
Authors: Horák Jakub
Published: July 2021

Niche partitioning among species with virtually the same requirements is a fundamental concept in ecology. Nevertheless, some authors suggest that niches have little involvement in structuring communities. This study was done in the Pardubice Region (Czech Republic) on saproxylic beetles with morphologically similar larvae and very specific requirements, which are related to their obligatory dependence on dead wood material: Cucujus cinnaberinus, Pyrochroa coccinea, and Schizotus pectinicornis. This work was performed on 232 dead wood pieces at the landscape scale over six years. Based on the factors studied, the relationships among these species indicated that their co-occurrence based on species presence and absence was low, which indicated niche partitioning. However, based on analyses of habitat requirements and species composition using observed species abundances, there was no strong evidence for niche partitioning at either studied habitat levels, the tree and the microhabitat. The most likely reasons for the lack of strong niche partitioning were that dead wood is a rich resource and co-occurrence of saproxylic community was not driven by resource competition. This might be consistent with the theory that biodiversity could be controlled by the neutral drift of species abundance. Nevertheless, niche partitioning could be ongoing, meaning that the expanding C. cinnaberinus may have an advantage over the pyrochroids and could dominate in the long term.
Multi-pass probing for high-sensitivity tomographic interferometry
Authors: Karatodorov Stefan , Lera Roberto , Raclavsky Marek , Lorenz Sebastian , Chaulagain Uddhab , Nejdl Jaroslav
Published: July 2021

Optical probing is an indispensable tool in research and development. In fact, it has always been the most natural way for humankind to explore nature. However, objects consisting of transparent materials with a refractive index close to unity, such as low-density gas jets, are a typical example of samples that often reach the sensitivity limits of optical probing techniques. We introduce an advanced optical probing method employing multiple passes of the probe through the object to increase phase sensitivity, and relay-imaging of the object between individual passes to preserve spatial resolution. An interferometer with four-passes was set up and the concept was validated by tomographic characterization of low-density supersonic gas jets. The results show an evident increase of sensitivity, which allows for the accurate quantitation of fine features such as a shock formed by an obstacle or a barrel shock on the jet boundary in low ambient gas pressures. Despite its limitations in temporal resolution, this novel method has demonstrated an increase in phase sensitivity in transmission, however, it can also be employed to boost the absorption or polarization contrast of weakly interacting objects in both transmission and reflection setups, thus, upgrading the sensitivity of various optical characterization methods.
Qualitative speed-accuracy tradeoff effects can be explained by a diffusion/fast-guess mixture model
Authors: Ratcliff Roger , Kang Inhan
Published: July 2021

Rafiei and Rahnev (2021) presented an analysis of an experiment in which they manipulated speed-accuracy stress and stimulus contrast in an orientation discrimination task. They argued that the standard diffusion model could not account for the patterns of data their experiment produced. However, their experiment encouraged and produced fast guesses in the higher speed-stress conditions. These fast guesses are responses with chance accuracy and response times (RTs) less than 300 ms. We developed a simple mixture model in which fast guesses were represented by a simple normal distribution with fixed mean and standard deviation and other responses by the standard diffusion process. The model fit the whole pattern of accuracy and RTs as a function of speed/accuracy stress and stimulus contrast, including the sometimes bimodal shapes of RT distributions. In the model, speed-accuracy stress affected some model parameters while stimulus contrast affected a different one showing selective influence. Rafiei and Rahnev’s failure to fit the diffusion model was the result of driving subjects to fast guess in their experiment.
Deep radiomics-based survival prediction in patients with chronic obstructive pulmonary disease
Authors: Yun Jihye , Cho Young Hoon , Lee Sang Min , Hwang Jeongeun , Lee Jae Seung , Oh Yeon-Mok , Lee Sang-Do , Loh Li-Cher , Ong Choo-Khoon , Seo Joon Beom , Kim Namkug
Published: July 2021

Heterogeneous clinical manifestations and progression of chronic obstructive pulmonary disease (COPD) affect patient health risk assessment, stratification, and management. Pulmonary function tests are used to diagnose and classify the severity of COPD, but they cannot fully represent the type or range of pathophysiologic abnormalities of the disease. To evaluate whether deep radiomics from chest computed tomography (CT) images can predict mortality in patients with COPD, we designed a convolutional neural network (CNN) model for extracting representative features from CT images and then performed random survival forest to predict survival in COPD patients. We trained CNN-based binary classifier based on six-minute walk distance results (> 440 m or not) and extracted high-throughput image features (i.e., deep radiomics) directly from the last fully connected layer of it. The various sizes of fully connected layers and combinations of deep features were experimented using a discovery cohort with 344 patients from the Korean Obstructive Lung Disease cohort and an external validation cohort with 102 patients from Penang General Hospital in Malaysia. In the integrative analysis of discovery and external validation cohorts, with combining 256 deep features from the coronal slice of the vertebral body and two sagittal slices of the left/right lung, deep radiomics for survival prediction achieved concordance indices of 0.8008 (95% CI, 0.7642–0.8373) and 0.7156 (95% CI, 0.7024–0.7288), respectively. Deep radiomics from CT images could be used to predict mortality in COPD patients.
Taiwan’s ecological footprint and overshoot day
Authors: Lee Yung-Jaan , Chai Lei , Wu Po-Shu
Published: July 2021

This study examines Taiwan’s ecological footprint (EF) and its Overshoot Day from 2000 to 2018. The latest EF calculation method is used to determine the conversion rates and equivalent factors of bioproductive lands in each year to establish a database of Taiwan’s EF in that period. The results reveal that Taiwan’s EF was 7.69 gha/person in 2000, dropping steadily to 6.46 gha/person in 2018. Taiwan’s carbon footprint accounted for about 61% of Taiwan’s total EF, slightly higher than the world average (60%). The carbon footprint as a proportion of the total EF has been increasing annually. This study adopts social communication tools, such as the overshoot day and the earth clock, to promote sustainable development goals and climate change policy initiatives. Global Footprint Network (GFN) updates the overshoot day of each country in its database yearly, based on each country’s EF and biocapacity. Since Taiwan is not included in GFN, this study adopts the same method and finds out that Taiwan's Overshoot Day in 2018 was March 14th, meaning that on March 14th, 2018, Taiwan exhausted all of the biological resources that its bioproductive lands can regenerate in the year. If the global population lived like Taiwanese, four Earths would be required to provide the resources used. This result not only reflects the consumption of natural resources in Taiwan, but also indicates that Taiwan should focus on sustainable development and reduce that consumption.
Role and effectiveness of complex and supervised rehabilitation on overall and hand function in systemic sclerosis patients—one-year follow-up study
Authors: Waszczykowski Michał , Dziankowska-Bartkowiak Bożena , Podgórski Michał , Fabiś Jarosław , Waszczykowska Arleta
Published: July 2021

The aim of this study was to estimate the long-term results of complex and supervised rehabilitation of the hands in systemic sclerosis (SSc) patients. Fifty-one patients were enrolled in this study: 27 patients (study group) were treated with a 4-week complex, supervised rehabilitation protocol. The control group of 24 patients was prescribed a home exercise program alone. Both groups were evaluated at baseline and after 1-, 3-, 6-, and 12-months of follow-up with the Disability of the Arm, Shoulder and Hand Questionnaire (DAHS) as the primary outcome, pain (VAS—visual analog scale), Cochin Hand Function Scale (CHFS), Health Assessment Questionnaire Disability Index (HAQ-DI), Scleroderma-HAQ (SHAQ), range of motion (d-FTP—delta finger to palm, Kapandji finger opposition test) and hand grip and pinch as the secondary outcomes. Only the study group showed significant improvements in the DASH, VAS, CHFS and SHAQ after 1, 3 and 6 months of follow-up (P = 0.0001). Additionally, moderate correlations between the DASH, CHFS and SHAQ (R = 0.7203; R = 0.6788; P = 0.0001) were found. Complex, supervised rehabilitation improves hand and overall function in SSc patients up to 6 months after the treatment but not in the long term. The regular repetition of this rehabilitation program should be recommended every 3–6 months to maintain better hand and overall function.
Detectability of pulmonary ossifications in fibrotic lung on ultra-high-resolution CT using 2048 matrix size and 0.25-mm slice thickness
Authors: Hata Akinori , Yanagawa Masahiro , Tsubamoto Mitsuko , Doi Shuhei , Yoshida Yuriko , Miyata Tomo , Kikuchi Noriko , Kashiwagi Nobuo , Tomiyama Noriyuki
Published: July 2021

To investigate the prevalence of nodular pulmonary ossifications (POs) in patients with honeycombing on ultra-high-resolution CT (UHRCT) and to compare the detectability of nodular POs between images reconstructed using the ultra-high-resolution setting (UHR-setting) and those using the conventional setting (C-setting) on UHRCT. Twenty patients with honeycombing in the lung were evaluated retrospectively. All patients underwent non-contrast-enhanced UHRCT. Images were reconstructed with UHR-setting (matrix, 2048 × 2048; slice thickness, 0.25 mm) and with C-setting (matrix size, 512 × 512; slice thickness, 0.5 mm). Two chest radiologists independently recorded the number of nodular POs (< 4 mm diameter) in each lung lobes. Each lobe was classified as one of the following five categories according to the number of POs: C0, none; C1, 1–4 POs; C2, 5–9 POs; C3, 10–49 POs; and C4, ≥ 50 POs. The maximum CT values of the POs were measured and compared between the two settings. PO categories were significantly higher with UHR-setting than with C-setting (p < 0.001). Maximum CT values were significantly higher with UHR-setting than with C-setting (p < 0.001). Nodular POs were seen in 80% or more of patients with honeycombing and more easily detected in images reconstructed with UHR-setting than in those with C-setting.
Efficient plant regeneration from embryogenic cell suspension cultures of Euonymus alatus
Authors: Woo Hyun-A , Ku Seong Sub , Jie Eun Yee , Kim HyeRan , Kim Hyun-Soon , Cho Hye Sun , Jeong Won-Joong , Park Sang Un , Min Sung Ran , Kim Suk Weon
Published: July 2021

To establish an efficient plant regeneration system from cell suspension cultures of Euonymus alatus, embryogenic callus formation from immature embryos was investigated. The highest frequency of embryogenic callus formation reached 50% when the immature zygotic embryos were incubated on Murashige and Skoog (MS) medium supplemented with 1 mg/L 2,4-dichlorophenoxy acetic acid (2,4-D). At higher concentrations of 2,4-D (over 2 mg/L), the frequency of embryogenic callus formation declined significantly. The total number of somatic embryos development was highest with the 3% (w/v) sucrose treatment, which was found to be the optimal concentration for somatic embryo formation. Activated charcoal (AC) and 6-benzyladenine (BA) significantly increased the frequency of plantlet conversion from somatic embryos, but gibberellic acid (GA3) had a negative effect on plantlet conversion and subsequent development from somatic embryos. Even though the cell suspension cultures were maintained for more than 1 year, cell aggregates from embryogenic cell suspension cultures were successfully converted into normal somatic embryos with two cotyledons. To our knowledge, this is the first successful report of a plant regeneration system of E. alatus via somatic embryogenesis. Thus, the embryogenic cell line and plant regeneration system established in this study can be applied to mass proliferation and production of pharmaceutical metabolite in E. alatus.
Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits
Authors: Thouta Samrat , Zhang Yiming , Garcia Esperanza , Snutch Terrance P.
Published: July 2021

Kv1.1 containing potassium channels play crucial roles towards dampening neuronal excitability. Mice lacking Kv1.1 subunits (Kcna1−/−) display recurrent spontaneous seizures and often exhibit sudden unexpected death. Seizures in Kcna1−/− mice resemble those in well-characterized models of temporal lobe epilepsy known to involve limbic brain regions and spontaneous seizures result in enhanced cFos expression and neuronal death in the amygdala. Yet, the functional alterations leading to amygdala hyperexcitability have not been identified. In this study, we used Kcna1−/− mice to examine the contributions of Kv1.1 subunits to excitability in neuronal subtypes from basolateral (BLA) and central lateral (CeL) amygdala known to exhibit distinct firing patterns. We also analyzed synaptic transmission properties in an amygdala local circuit predicted to be involved in epilepsy-related comorbidities. Our data implicate Kv1.1 subunits in controlling spontaneous excitatory synaptic activity in BLA pyramidal neurons. In the CeL, Kv1.1 loss enhances intrinsic excitability and impairs inhibitory synaptic transmission, notably resulting in dysfunction of feed-forward inhibition, a critical mechanism for controlling spike timing. Overall, we find inhibitory control of CeL interneurons is reduced in Kcna1−/− mice suggesting that basal inhibitory network functioning is less able to prevent recurrent hyperexcitation related to seizures.
Health-related quality of life in ICU survivors—10 years later
Authors: Hofhuis José G. M. , Schrijvers Augustinus J. P. , Schermer Tjard , Spronk Peter E.
Published: July 2021

Many Intensive Care (ICU) survivors experience long lasting impairments in physical and psychological health as well as social functioning. The objective of our study was to evaluate these effects up to 10 years after ICU discharge. We performed a long-term prospective cohort study in patients admitted for longer than 48 h in a medical-surgical ICU. We evaluated health-related quality of life (HRQOL) before ICU admission using the Short-form-36 (SF-36), at ICU discharge, at hospital discharge and at 1, 2, 5 and 10 years follow up (all by patients). Changes in HRQOL were assessed based on linear mixed modeling. We included a total of 749 patients (from 2000 to 2008). During 10 years 475 (63.4%) patients had died, 125 (16.7%) patients were lost to follow up and 149 (19.9%) patients could be evaluated. The mean scores of four HRQOL dimensions (i.e., physical functioning (p < 0.001; mean 54, SD 32, effect size 0.77, 95% CI [0.54–1.0]), role-physical (p < 0.001; mean 44, SD 47, effect size 0.65, 95% CI [0.41–0.68] general health (p < 0.001; mean 52, SD 27, effect size 0.48; 95% CI 0.25–0.71) and social functioning (p < 0.001; mean 72, SD 32, effect size 0.41, 95% CI [0.19–0.64]) were still lower 10 years after ICU discharge compared with pre-admission levels (n = 149) and with an age reference population. Almost all SF-36 dimensions changed significantly over time from ICU discharge up to 10 years after ICU discharge. Over the 10 year follow up physical functioning of medical-surgical ICU survivors remains impaired compared with their pre-admission values and an age reference population. However, effect sizes showed no significant differences suggesting that surviving patients largely regained their age-specific HRQOL at 10 years.
High thermal durability of Ru-based synthetic antiferromagnet by interfacial engineering with Re insertion
Authors: Yang Chun-Liang , Lai Chih-Huang
Published: July 2021

Synthetic antiferromagnets (SAFs), composed of Ru spacer with a Re insertion layer, reveal superior thermal stability up to 450 °C annealing, making the back-end of line process a wider manufacturing window and tolerance to integrate the perpendicular magnetic tunneling junctions (P-MTJs) into CMOS process. The coupling strength decays significantly for SAFs with single Ru spacer after annealing above 400 °C. Due to the characteristics of refractory metals, Re can behave as a diffusion barrier during annealing. Furthermore, the Re spacer can still keep reasonable RKKY coupling strength. Therefore, the SAFs with Ru/Re composite spacers exhibit higher RKKY coupling strength than Ru spacers after 450 °C annealing. In addition, we discovered the different enhancements for the upper and lower interfacial Re insertion, which was attributed to the varied defect formation at interfaces. The stacking fault was formed at the upper Ru/Co interface in as-deposited state. When Re was inserted at the upper interface, the diffusion between Co and Ru was significantly suppressed and the stacking fault can be eliminated during annealing, leading to enhanced interlayer coupling. Through the interfacial engineering, we may have more degrees of freedom to tune the SAF performance and thus enhance process compatibility of P-MTJ to the CMOS process.
Predictability of sinusoidally moving stimuli does not improve the accuracy of the accommodative response
Authors: Águila-Carrasco Antonio J. Del , Marín-Franch Iván
Published: July 2021

Previous research work suggests that predictable target motion such as sinusoidal movement can be anticipated by the visual system, thereby improving the accommodative response. The validity of predictable motion for studying human dynamic accommodation is sometimes put into question. The aim of this work was to assess the effect of anticipation along with learning (and motivation, etc.) and fatigue (and boredom, loss of attention, etc.) on dynamic accommodation experiments from a practical perspective. Specifically, changes in amplitude and temporal phase lag were estimated within and between trials as 9 adult observers were instructed to focus on a stimulus that oscillated sinusoidally towards and away from the eye at specific temporal frequencies. On average, amplitude decreased whereas phase increased within trials. No evidence of anticipation or learning was observed either within or between trials. Fatigue consistently dominated anticipation and learning within the course of each trial. Even if the eye is equipped by a prediction operator as it is often assumed, fatigue confounds the results from dynamic accommodation experiments more than anticipation or learning.
Incidence, demographics, and survival of patients with primary pituitary tumors: a SEER database study in 2004–2016
Authors: Chen Cheng , Hu Yu , Lyu Liang , Yin Senlin , Yu Yang , Jiang Shu , Zhou Peizhi
Published: July 2021

Comprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Extensive clinical and demographic characteristics were extracted and submitted to group comparisons. The standardized incidence rate was calculated and stratified by year at diagnosis, age/sex and age/treatment groups. The Kaplan–Meier analysis and multivariable regressions were performed to identify the factors associated with overall survival. A total of 47,180 pituitary tumors were identified, including 47,030 typical adenomas, 111 uncertain behavior pituitary adenomas, and 39 pituitary carcinomas. The overall standardized incidence rate was 4.8 cases per 100,000 person-years and the annual incidence rate continually trended upwards, with a peak seen in 2015. We noticed a bimodal age-related distribution in females and a unimodal distribution in males. In the multivariate regression analysis, the factors associated with prolonged survival included typical adenoma, younger age, and smaller tumor size. Whereas, black and male patients had worse overall survival. Our study provides a reliable estimate on the incidence of pituitary adenoma and confirms that the annual standardized incidence rate is increasing. Pituitary adenomas have a satisfactory long-term prognosis and age, tumor size, and tumor subtypes are related to overall survival. Though statistically significant, our inferential findings should be constrained within the limitations of SEER database.
Profiles for identifying problematic dietary habits in a sample of recreational Spanish cyclists and triathletes
Authors: Muros José J. , Knox Emily , Hinojosa-Nogueira Daniel , Rufián-Henares José Á. , Zabala Mikel
Published: July 2021

There is a lack of sufficient information on the dietary intake and nutritional supplementation of recreational endurance athletes throughout the year. The present observational study sought to assess the dietary intake and nutritional supplementation habits of recreational cyclists and triathletes from Spain. 4,037 cyclists and triathletes completed self-report measures. Nutritional profiles were developed and differences were examined according to sporting discipline and gender. Differences between groups were compared using the Mann–Whitney U or chi-squared test. Next, micro- and macro-nutrients were grouped according to whether or not guideline intake amounts were met. The clustering of dietary habits was then examined via K-means cluster analysis. Triathletes took more supplements than cyclists (X2 = 36.489; p value = .000) and females took more supplements than males (X2 = 5.920; p value = .017). Females and triathletes reported greater protein and CHO consumption than males and cyclists, respectively. Triathletes also reported a higher consumption of total fat, MUFA, PUFA, EPA, DHA and fibre. Females and triathletes tended to consume more vitamins and minerals than males and cyclists, respectively. Two main dietary habit clusters emerged which may be used to inform nutritional interventions targeting recreational athletes not meeting nutritional requirements. There is an imbalance in the main nutrients making up the diet of recreational Spanish athletes, characterised by insufficient CHO and excessive protein.
Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)
Authors: Es Hamidreza Aboulkheyr , Mahdizadeh Hamid , Asl Amir Abbas Hedayati , Totonchi Mehdi
Published: July 2021

Carcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is the only state-of-art treatment option for CUP patients. The molecular profiling of the tumour, particularly mutation detection, offers a new treatment approach for CUP in a personalized fashion using targeted agents. We analyzed the mutation and copy number alterations profile of 1709 CUP samples deposited in the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) cohort and explored potentially druggable mutations. We identified 52 significant mutated genes (SMGs) among CUP samples, in which 13 (25%) of SMGs were potentially targetable with either drugs are approved for the know primary tumour or undergoing clinical trials. The most variants detected were TP53 (43%), KRAS (19.90%), KMT2D (12.60%), and CDKN2A (10.30%). Additionally, using pan-cancer analysis, we found similar variants of TERT promoter in CUP and NSCLC samples, suggesting that these mutations may serve as a diagnostic marker for identifying the primary tumour in CUP. Taken together, the mutation profiling analysis of the CUP tumours may open a new way of identifying druggable targets and consequently administrating appropriate treatment in a personalized manner.
Faecal biomarkers in type 1 diabetes with and without diabetic nephropathy
Authors: Winther Signe Abitz , Mannerla Miia Maininki , Frimodt-Møller Marie , Persson Frederik , Hansen Tine Willum , Lehto Markku , Hörkkö Sohvi , Blaut Michael , Forsblom Carol , Groop Per-Henrik , Rossing Peter
Published: July 2021

Gastrointestinal dysbiosis is common among persons with type 1 diabetes (T1D), but its potential impact on diabetic nephropathy (DN) remains obscure. We examined whether faecal biomarkers, previously associated with low-grade gastrointestinal inflammation, differ between healthy controls and T1D subjects with and without DN. Faecal samples were analyzed for levels of calprotectin, intestinal alkaline phosphatase (IAP), short-chain fatty acids (SCFA) and immunoglobulins in subjects with T1D (n = 159) and healthy controls (NDC; n = 50). The subjects with T1D were stratified based on albuminuria: normoalbuminuria (< 30 mg/g; n = 49), microalbuminuria (30–299 mg/g; n = 50) and macroalbuminuria (≥ 300 mg/g; n = 60). aecal calprotectin, IAP and immunoglobulin levels did not differ between the T1D albuminuria groups. However, when subjects were stratified based on faecal calprotectin cut-off level (50 µg/g), macroalbuminuric T1D subjects exceeded the threshold more frequently than NDC (p = 0.02). Concentrations of faecal propionate and butyrate were lower in T1D subjects compared with NDC (p = 0.04 and p = 0.03, respectively). Among T1D subjects, levels of branched SCFA (BCFA) correlated positively with current albuminuria level (isobutyrate, p = 0.03; isovalerate, p = 0.005). In our study cohort, fatty acid metabolism seemed to be altered among T1D subjects and those with albuminuria compared to NDC. This may reflect gastrointestinal imbalances associated with T1D and renal complications.
Genetic architecture of type 1 diabetes with low genetic risk score informed by 41 unreported loci
Authors: Qu Hui-Qi , Qu Jingchun , Bradfield Jonathan , Marchand Luc , Glessner Joseph , Chang Xiao , March Michael , Li Jin , Connolly John J. , Roizen Jeffrey D. , Sleiman Patrick , Polychronakos Constantin , Hakonarson Hakon
Published: July 2021

Type 1 diabetes (T1D) patients with low genetic risk scores (GRS) may be non-autoimmune or autoimmune mediated by other genetic loci. The T1D-GRS2 provides us an opportunity to look into the genetic architecture of these patients. A total of 18,949 European individuals were included in this study, including 6599 T1D cases and 12,323 controls. 957 (14.5%) T1D patients were identified with low GRS (GRS < 8.43). The genome-wide association study on these patients identified 41 unreported loci. Two loci with common variants and 39 loci with rare variants were identified in this study. This study identified common SNPs associated with both low GRS T1D and expression levels of the interferon-α-inducedMNDAgene, indicating the role of viral infection in T1D. Interestingly, 16 of the 41 unreported loci have been linked to autism spectrum disorder (ASD) by previous studies, suggesting that genes residing at these loci may underlie both T1D and autism.