bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Care Implications of Terrorist Attacks in South Asia
Authors: Tin Derrick , Abelanes Sally-Mae , Bin Adnan Mohd Syafwan , Kole Tamorish , Ciottone Gregory R.
Published: April 2022

Background:

The recent United States (US) troop withdrawal out of Afghanistan under a February 2020 US-Taliban agreement and the rapid concurrent collapse of the Afghan military, followed by the ascendance of the Taliban, has placed an international spotlight around the future of South Asian countries. Security threats, in particular, will likely escalate within the region and beyond, with significant concerns around the resurgence of terrorism and violence in the region. This study aims to provide an epidemiological description of all terrorism-related attacks in South Asia sustained from 1970 – 2019. These data will be useful in the development of education programs in Counter-Terrorism Medicine and provide an insight into potential attacks in the future.

Methods:

Data collection was performed using a retrospective database search through the Global Terrorism Database (GTD). The GTD was searched using the internal database search functions for all events which occurred in Afghanistan, Bangladesh, Bhutan, India, Maldives, Mauritius, Nepal, Pakistan, and Sri Lanka (collectively referred to as South Asia) from January 1, 1970 - December 31, 2019. Primary weapon type, primary target type, country where the incident occurred, and number of deaths and injuries were collated and exported for analysis.

Results:

In total, 23.69% of all terrorist attacks from 1970-2019 occurred in the South Asia region, causing 96,092 deaths and 141,333 non-fatal injuries. Of those, 50.1% of attacks in South Asia used explosives, 31.9% used firearms, 9.4% used unknown weapons, 5.9% used incendiary attacks, 2.3% were melee attacks, and <0.5% used chemical, biological, and other weapon types.

Conclusion:

Over 88% of the attacks occurred in Afghanistan, Pakistan, and India combined. While there has been a decline in attacks since a peak in 2014, there are concerns of a significant increase in terrorism activity in recent months which could impact an already fragmented health care system. The use of explosives and firearms as attack modalities accounted for 82.0 % of all weapon types used, but the impact of terrorism and conflict expands beyond simple death and casualty tolls.
Exploring the association of dietary patterns with the risk of hypertension using principal balances analysis and principal component analysis
Authors: Zhao Junkang , Guo Wenjing , Wang Juping , Wang Tong
Published: April 2022

Objective:

In the field of nutritional epidemiology, principal component analysis (PCA) has been used extensively in identifying dietary patterns. Recently, compositional data analysis (CoDA) has emerged as an alternative approach for obtaining dietary patterns. We aimed to directly compare and evaluate the ability of PCA and principal balances analysis (PBA), a data-driven method in CoDA, in identifying dietary patterns and their associations with the risk of hypertension.

Design:

Cohort study. A 24-h dietary recall questionnaire was used to collect dietary data. Multivariate logistic regression analysis was used to analyse the association between dietary patterns and hypertension.

Setting:

2004 and 2009 China Health and Nutrition Survey.

Participants:

A total of 3892 study participants aged 18–60 years were included as the subjects.

Results:

PCA and PBA identified five patterns each. PCA patterns comprised a linear combination of all food groups, whereas PBA patterns included several food groups with zero loadings. The coarse cereals pattern identified by PBA was inversely associated with hypertension risk (highest quintile: OR = 0·74 (95 % CI 0·57, 0·95); Pfor trend = 0·037). None of the five PCA patterns was associated with hypertension. Compared with the PCA patterns, the PBA patterns were clearly interpretable and accounted for a higher percentage of variance in food intake.

Conclusions:

Findings showed that PBA might be an appropriate and promising approach in dietary pattern analysis. Higher adherence to the coarse cereals dietary pattern was associated with a lower risk of hypertension. Nevertheless, the advantages of PBA over PCA should be confirmed in future studies.
Design of dual band-notched UWB hexagonal printed microstrip antenna
Authors: Mukherjee Surajit , Roy Avisankar , Maity Smarajit , Tewary Tapas , Sarkar Partha Pratim , Bhunia Sunandan
Published: April 2022

This article presents the design and performance analysis of a printed microstrip ultra-wideband (UWB) antenna consisting of the slots in the ground plane and radiating patch. A meandered S-shaped slot has been introduced on the patch and an inverted U-shaped slot has been incorporated in the ground plane to realize the band-notch effect for WiMAX (3.2–3.8 GHz) and WLAN (5.1–5.8 GHz) bands respectively. The total dimension of the proposed design is 44 × 44 mm2. The fabricated antenna exhibits wide impedance bandwidth of 10 GHz (2.4–12.4 GHz), i.e., 135% of center frequency. The design prototype is fabricated, and the measured results have good agreement with simulated values. The effects of the slots have been analyzed by simulated surface current distribution. The designed antenna shows almost omnidirectional radiation patter and stable gain. The proposed hexagonal antenna may be suitable for UWB applications removing WiMAX and WLAN bands.
Seed germination ecology of leucaena (Leucaena leucocephala) as influenced by various environmental parameters
Authors: Dhanda Sachin , Chauhan Bhagirath Singh
Published: April 2022

Leucaena [Leucaena leucocephala (Lam.) de Wit] is a perennial weed in more than 25 countries, including Australia. Knowledge regarding the seed biology of L. leucocephala could help in making weed management decisions. Experiments were conducted to study the effect of hot water (scarification), alternating temperatures, heat stress, salt stress, water stress, and burial depth on seed germination of two populations of L. leucocephala collected from Toowoomba and Gatton, Australia. The optimum duration of hot water treatment to break the hard seed coat dormancy was 2 min for both populations. The highest germination (92% to 98%) was recorded at 35/25 C for both populations, and similar germination occurred at 30/20 C. The Toowoomba population recorded greater germination at low temperature (15/5 to 25/15 C) than the Gatton population. Additionally, the Gatton population had higher germination than the Toowoomba population after 5 min of exposure to temperatures of up to 100 C, suggesting that the Gatton population may be more tolerant to heat stress. Germination was completely inhibited at pretreatment (5 min) temperatures of 150 to 250 C. The Toowoomba population recorded 17% greater germination than the Gatton population at a high salt concentration (160 mM NaCl), indicating its greater salt tolerance. At low moisture stress (−0.1 and −0.2 MPa), higher germination was observed in the Toowoomba population than in the Gatton population, whereas germination was similar for both populations at higher water stress levels (−0.4 MPa or lower). Germination was similar for both populations at shallow depths (0 and 1 cm) but higher emergence was recorded for the Toowoomba population at 2 to 8 cm than the Gatton population. Differential germination behaviors of both populations suggest that they adapted differently in their respective local environments. Knowledge gained from this study will help in formulating integrated management practices for L. leucocephala.
Lived Future in Addiction
Authors: Moskalewicz Marcin , Messas Guilherme
Published: April 2022

Abstract: Aim: The article presents the basic tenants of dialectical phenomenological psychopathology (DPP) of temporal experience in substance-related disorders. Results: DPP examines the conditions of possibility of lived experiences. It goes beyond mere qualitative descriptions of subjective psychological states to identify their pre-reflective structures. The modifications of these structures are considered essential to mental disorders, including additions. The paper argues that the phenomenon of addiction arises when there is a failure of the dynamic process of temporal balances and imbalances between the dimensions of lived past, present, and future. In such an altered state, the present pathologically dominates over past and future. Personal history and future consequences of intoxicated behaviour are disregarded. The future in particular loses its ‘normal’ characteristic of a probable horizon of present experience and becomes ‘actualized’ as present continuous. At the same time, a part of the future ‘dissociates’ from the present objective situation and becomes improbable. To substantiate these claims, the article presents four case vignettes of clients suffering from such pathological entanglement of temporal dimensions. Conclusions: DPP may be seen as an invaluable approach to examine the dialectical structure of human experience. As such, it constitutes a promising paradigm for the 21st century person-centered psychiatry.
Eine Frau mit Unruhe und Synkopen im Altersheim
Authors: Hodel Vera , Flury Gian
Published: April 2022

Zusammenfassung. Synkopen haben eine breite Differenzialdiagnose. Am häufigsten sind kardiovaskuläre und neurologische Ursachen. Bei Krampfanfällen mit plötzlichen Tonusverlusten müssen neben einer Epilepsie auch iktal getriggerte Arrhythmien gesucht werden. Iktale Bradykardien und Asystolien sind meist benigne und selbstlimitierend. Im Gegensatz dazu sind Bradykardien und Asystolien im Rahmen eines SUDEP meist fatal und Folge einer iktal induzierten zerebralen Hypoxämie.
Examining Relationships Between Groundwater Nitrate Concentrations in Drinking Water and Landscape Characteristics to Understand Health Risks
Authors: Hamlin Q. F. , Martin S. L. , Kendall A. D. , Hyndman D. W.
Published: April 2022

Nitrate ingested from drinking water has been linked to adverse health outcomes (e.g., cancer, birth defects) at levels as low as ∼2 mg/L NO3‐N, far below the regulatory limits of 10 mg/L. In many areas, groundwater is a common drinking water source and may contain elevated nitrate, but limited data on the patterns and concentrations are available. Using an extensive regulatory data set of over 100,000 nitrate drinking water well samples, we developed new maps of groundwater nitrate concentrations from 76,724 wells in Michigan's Lower Peninsula, USA for the 2006–2015 period. Kriging, a geostatistical method, was used to interpolate concentrations and quantify probability of exceeding relevant thresholds (>0.4 [common detection limit], >2 mg/L NO3‐N). We summarized this probability in small watersheds (∼80 km2) to identify correlated variables using the machine learning method classification and regression trees (CARTs). We found 79% of wells had concentrations below the detection limit in this analysis (<0.4 mg/L NO3‐N). In the shallow aquifer (focus of study), 13% of wells exceeded 2 mg/L NO3‐N and 2% exceeded the EPA maximum contaminant level of 10 mg/L. CART explained 40%–45% of variation in each model and identified three categories of critical correlated variables: source (high agricultural nitrogen inputs), vulnerable soil conditions (low soil organic carbon and high hydraulic conductivity), and transport mechanisms (high aquifer recharge). These findings add to the body of literature seeking to identify communities at risk of elevated nitrate and study associated adverse health outcomes.
Rate and State Friction as a Spatially Regularized Transient Viscous Flow Law
Authors: Pranger Casper , Sanan Patrick , May Dave A. , Le Pourhiet Laetitia , Gabriel Alice‐Agnes
Published: April 2022

The theory of rate and state friction unifies field, laboratory, and theoretical analysis of the evolution of slip on natural faults. While the observational study of earthquakes and aseismic fault slip is hampered by its strong multi‐scale character in space and time, numerical simulations are well‐positioned to link the laboratory study of grain‐scale processes to the scale at which rock masses move. However, challenges remain in accurately representing the complex and permanently evolving sub‐surface fault networks that exist in nature. Additionally, the common representation of faults as interfaces may miss important physical aspects governing volumetric fault system behavior. In response, we propose a transient viscous rheology that produces shear bands that closely mimic the rate‐ and state‐dependent sliding behavior of equivalent fault interfaces. Critically, we show that the expected tendency of the continuum rheology for runaway localization and mesh dependence can be halted by including an artificial diffusion‐type regularization of anelastic strain rate in the softening law. We demonstrate analytically and numerically using a simplified fault transect that important aspects of the frictional behavior are not significantly affected by the introduced regularization. Any discrepancies with respect to the interfacial description of fault behavior are critically evaluated using one dimensional numerical velocity stepping and spring‐slider experiments. Since no new physical parameters are introduced, our model may be straightforwardly used to extend the existing modeling techniques. The model predicts the emergence of complex patterns of shear localization and delocalization that may inform the interpretation of complex damage distributions observed around faults in nature.
Biogeochemical Equilibrium Responses to Maximal Productivity in High Nutrient Low Chlorophyll Regions
Authors: Fu Weiwei , Wang Wei‐Lei
Published: April 2022

Whether ocean iron fertilization in high nutrient low chlorophyll (HNLC) regions is a practical geoengineering strategy to combat climate warming has been debated because the fate of absorbed carbon by the ocean remains unclear. We use an optimized oceanic biogeochemical inverse model to explore the equilibrium responses to increased productivity in major HNLC regions. We find that an overall downward shift of nutrients and carbon from the surface and intermediate to the deep waters with maximal productivity in the HNLC Southern Ocean (SO), North Pacific (NP) and eastern equatorial Pacific (EP). The efficiency of soft tissue pump is increased by 37.8%, 2.7% and 5.4% in the SO, EP and NP simulation while atmospheric CO2 concentration is drawn down by 45.1, 3.4 and 6.7 ppm, respectively. Meanwhile, global mean oxygen is decreased by 21.1%, 1.3% and 2.4% in the SO, EP and NP simulation, accompanied by an expansion of oxygen minimum zones by 400%, 26% and 63%, respectively. Our study indicates that iron fertilization has the potential to be an effective geoengineering approach to mitigate climate warming but also has a strong impact on the development of ocean hypoxia.
Remote Sensing of Mid‐Latitude Ionospheric Magnetic Field Fluctuations Using Cosmic Radio Sources
Authors: Helmboldt J. F. , Clarke T. E. , Kassim N. E.
Published: April 2022

This paper describes a new method for remote sensing of magnetic field fluctuations at ionospheric altitudes using a relatively long‐baseline interferometer and exceptionally bright cosmic radio sources at 35 MHz. The technique uses sensitive measurements of the difference in phase between two phased array telescopes separated by about 75 km and between the right and left circular polarizations to measure the amount of differential Faraday rotation. Combined with estimates of the background magnetic field and total electron content, these can be converted to measurements of fluctuations in the differential magnetic field parallel to the line of sight, ΔB‖. The temporal gradient in ΔB‖ roughly follows the diurnal pattern expected for B‖ due to the vertical gradient in the background electric field, but at roughly 25% the magnitude and offset by ∼50 nT hr−1. This suggests that the diurnal variation in the electric fields observed by the two telescopes are similar but slightly different (|ΔE| ≲ 0.1 mV m−1). Fluctuations in ΔB‖ were typically ∼10–30 nT with wavelike fluctuations often apparent. These typically have oscillation periods of about 10–30 min, similar to traveling ionospheric disturbances (TIDs). Simultaneous observations toward two sources separated by 25.4° on the sky (∼140 km in the F‐region) show a few detections of wavelike disturbances with lags of ±10–30 min between them. These imply speeds on the order of 100–200 m s−1, also similar to TIDs. We estimate that gravity waves with amplitudes within the dynamo region of ∼10 m s−1 could generate the observed fluctuations in ΔB‖.
Thank You to Our 2021 Peer Reviewers
Authors: Trumbore Susan , Barros Ana P. , Becker Thorsten W. , Davidson Eric A. , Ehlmann Bethany L. , Gruber Nicolas , Hofmann Eileen E. , Hudson Mary K. , Illangasekare Tissa H. , Kang Sarah , Montanari Alberto , Nimmo Francis , Parsons Tom , Salters Vincent J. M. , Schimel David , Stevens Bjorn , Wuebbles Donald J. , Zeitler Peter , Zhu Tong
Published: April 2022

The editorial board of AGU Advances thanks the individuals who reviewed for the journal in 2021.
Intensification of Pacific Trade Wind and Related Changes in the Relationship Between Sea Surface Temperature and Sea Level Pressure
Authors: Yang Fan , Zhang Lujun , Long Mengyuan
Published: April 2022

This study applies a quantitative method to analyze variation in Pacific trade winds in 1950–2020. It's found that the southeast and northeast trade winds enter an acceleration period since the mid to late 1990s while the wind are enhanced in each month of the year. The enhancement of southeast trade wind is less intense than that of northeast trade wind. Further analysis shows that after the acceleration, the correlation between sea level pressure/sea surface temperature (SST) and the trade wind speed in the Pacific subtropical high area are obviously strengthened. The negative correlation between sea level pressure and SST in this area is also enhanced, which may be due to the enhancement of trade wind that have caused a decrease in SST. The reduction further enhanced and maintained a higher sea level pressure, thus forming a configuration which is conducive to the intensification of trade wind.
High-performance polarization management devices based on thin-film lithium niobate
Authors: Lin Zhongjin , Lin Yanmei , Li Hao , Xu Mengyue , He Mingbo , Ke Wei , Tan Heyun , Han Ya , Li Zhaohui , Wang Dawei , Yao X. Steve , Fu Songnian , Yu Siyuan , Cai Xinlun
Published: April 2022

High-speed polarization management is highly desirable for many applications, such as remote sensing, telecommunication, and medical diagnosis. However, most of the approaches for polarization management rely on bulky optical components that are slow to respond, cumbersome to use, and sometimes with high drive voltages. Here, we overcome these limitations by harnessing photonic integrated circuits based on thin-film lithium niobate platform. We successfully realize a portfolio of thin-film lithium niobate devices for essential polarization management functionalities, including arbitrary polarization generation, fast polarization measurement, polarization scrambling, and automatic polarization control. The present devices feature ultra-fast control speeds, low drive voltages, low optical losses and compact footprints. Using these devices, we achieve high fidelity polarization generation with a polarization extinction ratio up to 41.9 dB and fast polarization scrambling with a scrambling rate up to 65 Mrad s−1, both of which are best results in integrated optics. We also demonstrate the endless polarization state tracking operation in our devices. The demonstrated devices unlock a drastically new level of performance and scales in polarization management devices, leading to a paradigm shift in polarization management.
Primary CD33-targeting CAR-NK cells for the treatment of acute myeloid leukemia
Authors: Albinger Nawid , Pfeifer Rita , Nitsche Marcus , Mertlitz Sarah , Campe Julia , Stein Katja , Kreyenberg Hermann , Schubert Ralf , Quadflieg Melissa , Schneider Dina , Kühn Michael W. M. , Penack Olaf , Zhang Congcong , Möker Nina , Ullrich Evelyn
Published: April 2022

Acute myeloid leukemia (AML) is a malignant disorder derived from neoplastic myeloid progenitor cells characterized by abnormal proliferation and differentiation. Although novel therapeutics have recently been introduced, AML remains a therapeutic challenge with insufficient cure rates. In the last years, immune-directed therapies such as chimeric antigen receptor (CAR)-T cells were introduced, which showed outstanding clinical activity against B-cell malignancies including acute lymphoblastic leukemia (ALL). However, the application of CAR-T cells appears to be challenging due to the enormous molecular heterogeneity of the disease and potential long-term suppression of hematopoiesis. Here we report on the generation of CD33-targeted CAR-modified natural killer (NK) cells by transduction of blood-derived primary NK cells using baboon envelope pseudotyped lentiviral vectors (BaEV-LVs). Transduced cells displayed stable CAR-expression, unimpeded proliferation, and increased cytotoxic activity against CD33-positive OCI-AML2 and primary AML cells in vitro. Furthermore, CD33-CAR-NK cells strongly reduced leukemic burden and prevented bone marrow engraftment of leukemic cells in OCI-AML2 xenograft mouse models without observable side effects.
Downregulation of REST in the cochlea contributes to age-related hearing loss via the p53 apoptosis pathway
Authors: Li Hongchen , Lu Mingshun , Zhang Haiwei , Wang Shengnan , Wang Fei , Ma Xueya , Liu Jiaxi , Li Xinyu , Yang Haichao , Shen Haitao , Lv Ping
Published: April 2022

Age-related hearing loss (AHL) is the most common sensory disorder amongst the elderly population. Although the degeneration of spiral ganglion neurons (SGNs) and hair cells (HCs) is considered to play a critical role in AHL, the mechanism has not been fully outlined. The repressor element 1-silencing transcription factor (REST) has recently been associated with mediating cell death in neurodegenerative diseases. However, whether REST induces degeneration of cochlear HCs and SGNs to contribute to AHL remains unknown. Here, we report that REST expression was decreased in HCs and SGNs in AHL mice. Conditional deletion ofRestin HCs and SGNs of 2-month-old mice resulted in hearing loss accompanied by the upregulation of p53, TNFR1(tumor necrosis factor receptor-1), and cleaved caspase-3. The p53 inhibitor pifithrin-α significantly attenuated SGN and HC damage and rescued hearing impairment inRestcKO mice. Furthermore, downregulation of REST by H2O2treatment induced apoptosis in the House Ear Institute Organ of Corti 1 cell, through the upregulation of p53. In contrast, overexpression of REST reversed the changes in p53 expression. In addition, REST was further shown to bind directly to the p53 promoter site, thereby inhibiting the effect of p53. Finally, in aged mice, the p53 inhibitor significantly reduced loss of HCs and SGNs, and subsequently improved hearing. In summary, our findings indicate that REST has a protective role in AHL, and that its deficiency upregulates p53 and induces cochlear cell apoptosis, which that leads to deafness.
TGF-β induces GBM mesenchymal transition through upregulation of CLDN4 and nuclear translocation to activate TNF-α/NF-κB signal pathway
Authors: Yan Tengfeng , Tan Yinqiu , Deng Gang , Sun Zhiqiang , Liu Baohui , Wang Yixuan , Yuan Fanen , Sun Qian , Hu Ping , Gao Lun , Tian Daofeng , Chen Qianxue
Published: April 2022

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. The unregulated expression of Claudin-4 (CLDN4) plays an important role in tumor progression. However, the biological role of CLDN4 in GBM is still unknown. This study aimed to determine whether CLDN4 mediates glioma malignant progression, if so, it would further explore the molecular mechanisms of carcinogenesis. Our results revealed that CLDN4 was significantly upregulated in glioma specimens and cells. The inhibition of CLND4 expression could inhibit mesenchymal transformation, cell invasion, cell migration and tumor growth in vitro and in vivo. Moreover, combined with in vitro analysis, we found that CLDN4 can modulate tumor necrosis factor-α (TNF-α) signal pathway. Meanwhile, we also validated that the transforming growth factor-β (TGF-β) signal pathway can upregulate the expression of CLDN4, and promote the invasion ability of GBM cells. Conversely, TGF-β signal pathway inhibitor ITD-1 can downregulate the expression of CLDN4, and inhibit the invasion ability of GBM cells. Furthermore, we found that TGF-β can promote the nuclear translocation of CLDN4. In summary, our findings indicated that the TGF-β/CLDN4/TNF-α/NF-κB signal axis plays a key role in the biological progression of glioma. Disrupting the function of this signal axis may represent a new treatment strategy for patients with GBM.
IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis
Authors: Song Chengcheng , Wang Shuqiang , Fu Zhangning , Chi Kun , Geng Xiaodong , Liu Chao , Cai Guangyan , Chen Xiangmei , Wu Di , Hong Quan
Published: April 2022

Renal inflammation is a critical pathophysiological characteristic of diabetic kidney disease (DKD). The mechanism of the inflammatory response is complicated, and there are few effective treatments for renal inflammation that can be used clinically. Insulin-like growth factor-binding protein 5 (IGFBP5) is an important secretory protein that is related to inflammation and fibrosis in several tissues. Studies have shown that the IGFBP5 level is significantly upregulated in DKD. However, the function of IGFBP5 and its mechanism in DKD remain unclear. Here, we showed that IGFBP5 levels were significantly increased in the kidneys of diabetic mice. Ablation of IGFBP5 alleviated kidney inflammation in DKD mice. Mechanistically, IGFBP5 increased glycolysis, which was characterized by increases in lactic acid and the extracellular acidification rate, by activating the transcription factor early growth response 1 (EGR1) and enhancing the expression of PFKFB3 in endothelial cells. Furthermore, a mutation in PFKFB3 attenuated renal inflammation in DKD mice. Taken together, we provided evidence that IGFBP5 enhanced kidney inflammation through metabolic reprogramming of glomerular endothelial cells. Our results provide new mechanistic insights into the effect of IGFBP5 on kidney and highlight potential therapeutic opportunities for IGFBP5 and the metabolic regulators involved in DKD.
Ultrastrong underwater adhesion on diverse substrates using non-canonical phenolic groups
Authors: Cheng Bohan , Yu Jinhong , Arisawa Toma , Hayashi Koki , Richardson Joseph J. , Shibuta Yasushi , Ejima Hirotaka
Published: April 2022

Robust underwater adhesion is challenging because a hydration layer impedes the interaction between substrates and adhesives. Phenolic adhesives inspired by marine creatures such as mussels were extensively studied, but these adhesives have not reached the adhesion strength and substrate diversity of Man-made dry adhesives. Here, we report a class of ultrastrong underwater adhesives with molecular phenolic designs extending beyond what nature has produced. These non-canonical phenolic polymers show versatile adhesion on various materials, with adhesion strengths exceeding 10 MPa on metal. Incorporating even just a small amount (<10%) of non-canonical phenolic groups into a polymer is sufficient for dramatically enhancing underwater adhesion, suggesting that this new class of phenolic materials will be incorporated into various industrial polymer systems in the future.
Structural basis for the assembly and quinone transport mechanisms of the dimeric photosynthetic RC–LH1 supercomplex
Authors: Cao Peng , Bracun Laura , Yamagata Atsushi , Christianson Bern M. , Negami Tatsuki , Zou Baohua , Terada Tohru , Canniffe Daniel P. , Shirouzu Mikako , Li Mei , Liu Lu-Ning
Published: April 2022

The reaction center (RC) and light-harvesting complex 1 (LH1) form a RC–LH1 core supercomplex that is vital for the primary reactions of photosynthesis in purple phototrophic bacteria. Some species possess the dimeric RC–LH1 complex with a transmembrane polypeptide PufX, representing the largest photosynthetic complex in anoxygenic phototrophs. However, the details of the architecture and assembly mechanism of the RC–LH1 dimer are unclear. Here we report seven cryo-electron microscopy (cryo-EM) structures of RC–LH1 supercomplexes fromRhodobacter sphaeroides. Our structures reveal that two PufX polypeptides are positioned in the center of the S-shaped RC–LH1 dimer, interlocking association between the components and mediating RC–LH1 dimerization. Moreover, we identify another transmembrane peptide, designated PufY, which is located between the RC and LH1 subunits near the LH1 opening. PufY binds a quinone molecule and prevents LH1 subunits from completely encircling the RC, creating a channel for quinone/quinol exchange. Genetic mutagenesis, cryo-EM structures, and computational simulations provide a mechanistic understanding of the assembly and electron transport pathways of the RC–LH1 dimer and elucidate the roles of individual components in ensuring the structural and functional integrity of the photosynthetic supercomplex.
Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer
Authors: Hao Yujun , He Baoyu , Wu Liping , Li Yamu , Wang Chao , Wang Ting , Sun Longci , Zhang Yanhua , Zhan Yangyang , Zhao Yiqing , Markowitz Sanford , Veigl Martina , Conlon Ronald A. , Wang Zhenghe
Published: April 2022

PI3Ks consist of p110 catalytic subunits and p85 regulatory subunits. PIK3CA, encoding p110α, is frequently mutated in human cancers. Most PIK3CA mutations are clustered in the helical domain or the kinase domain. Here, we report that p85β disassociates from p110α helical domain mutant protein and translocates into the nucleus through a nuclear localization sequence (NLS). Nuclear p85β recruits deubiquitinase USP7 to stabilize EZH1 and EZH2 and enhances H3K27 trimethylation. Knockout of p85β or p85β NLS mutant reduces the growth of tumors harboring a PIK3CA helical domain mutation. Our studies illuminate a novel mechanism by which PIK3CA helical domain mutations exert their oncogenic function. Finally, a combination of Alpelisib, a p110α-specific inhibitor, and an EZH inhibitor, Tazemetostat, induces regression of xenograft tumors harboring a PIK3CA helical domain mutation, but not tumors with either a WT PIK3CA or a PIK3CA kinase domain mutation, suggesting that the drug combination could be an effective therapeutic approach for PIK3CA helical domain mutant tumors.
CHD7 regulates bone-fat balance by suppressing PPAR-γ signaling
Authors: Liu Caojie , Xiong Qiuchan , Li Qiwen , Lin Weimin , Jiang Shuang , Zhang Danting , Wang Yuan , Duan Xiaobo , Gong Ping , Kang Ning
Published: April 2022

Chromodomain helicase DNA-binding protein 7 (CHD7), an ATP-dependent eukaryotic chromatin remodeling enzyme, is essential for the development of organs. The mutation of CHD7 is the main cause of CHARGE syndrome, but its function and mechanism in skeletal system remain unclear. Here, we show conditional knockout of Chd7 in bone marrow mesenchymal stem cells (MSCs) and preosteoblasts leads to a pathological phenotype manifested as low bone mass and severely high marrow adiposity. Mechanistically, we identify enhancement of the peroxisome proliferator-activated receptor (PPAR) signaling in Chd7-deficient MSCs. Loss of Chd7 reduces the restriction of PPAR-γ and then PPAR-γ associates with trimethylated histone H3 at lysine 4 (H3K4me3), which subsequently activates the transcription of downstream adipogenic genes and disrupts the balance between osteogenic and adipogenic differentiation. Our data illustrate the pathological manifestations of Chd7 mutation in MSCs and reveal an epigenetic mechanism in skeletal health and diseases.
Nasal symbiont Staphylococcus epidermidis restricts the cellular entry of influenza virus into the nasal epithelium
Authors: Jo Ara , Won Jina , Gil Chan Hee , Kim Su Keun , Lee Kang-Mu , Yoon Sang Sun , Kim Hyun Jik
Published: April 2022

Our recent study presented that human nasal commensal Staphylococcus epidermidis could potentiate antiviral immunity in the nasal mucosa through interferon-related innate responses. Here, we found that human nasal commensal S. epidermidis promoted protease–protease inhibitor balance in favor of the host and prevented influenza A virus (IAV) replication in the nasal mucosa and lungs. A relatively higher induction of Serpine1 exhibited in S. epidermidis-inoculated nasal epithelium and S. epidermidis-induced Serpine1 significantly decreased the expression of serine proteases. Furthermore, the transcription of urokinase plasminogen activator (uPA) and Serpine1 was biologically relevant in S. epidermidis-inoculated nasal epithelium, and the induction of uPA might be related to the sequential increase of Serpine1 in human nasal epithelium. Our findings reveal that human nasal commensal S. epidermidis manipulates the cellular environment lacking serine proteases in the nasal epithelium through Serpine1 induction and disturbs IAV spread to the lungs at the level of the nasal mucosa.
The upregulation of circFNDC3B aggravates the recurrence after endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) patients
Authors: Zhang Jing , Bai Jun , Zhu Hongbing , Li Wei , An Qunxing , Wang Dongxu
Published: April 2022

It has been reported that the expression of CD44 variant 9 could be utilized as a predictive marker for the recurrence in early gastric cancer (EGC) after endoscopic submucosal dissection (ESD). And circFNDC3B was proved to increase the migration and invasion of gastric cancer (GC) cells. In this study, we recruited 96 EGC patients after ESD treatment and grouped them into High circFNDC3B expression group (High expression group) and Low circFNDC3B expression group (Low expression group). Accordingly, we found that the recurrence-free rate in the High expression group was lower than that in the Low expression group. In the High expression group, the relative expression of miR-942 and miR-510 was both suppressed while the relative expression of CDH1 mRNA and CD44 mRNA/protein was increased compared with those in the Low expression group. CircFNDC3B was found to target miR-942 and miR-510 and suppress their expressions respectively. Moreover, miR-942 was found to target CD44 mRNA while miR-510 was found to target CDH1 mRNA. The overexpression of circFNDC3B led to the down-regulation of miR-942 and miR-510, which accordingly resulted in the up-regulation of CD44 and CDH1 in MKN28 cells. Moreover, we found H. pylori infection could promote the expression of circFNDC3B, which also resulted in up-regulated CD44 and CDH1 mRNA level in rTip-α cultivated MKN28 cells. In summary, our study demonstrated that a higher level of circFNDC3B could lead to the increased expression of CD44 and CDH1 via modulating the signaling pathways of miR-942/CD44 and miR-510/CDH1 in EGC patients. And the up-regulation of CD44 and CDH1 would accordingly result in a higher recurrence rate of EGC patients treated by ESD.
Evaluating efficacy of indoor non-pharmaceutical interventions against COVID-19 outbreaks with a coupled spatial-SIR agent-based simulation framework
Authors: Gunaratne Chathika , Reyes Rene , Hemberg Erik , O’Reilly Una-May
Published: April 2022

Contagious respiratory diseases, such as COVID-19, depend on sufficiently prolonged exposures for the successful transmission of the underlying pathogen. It is important that organizations evaluate the efficacy of non-pharmaceutical interventions aimed at mitigating viral transmission among their personnel. We have developed a operational risk assessment simulation framework that couples a spatial agent-based model of movement with an agent-based SIR model to assess the relative risks of different intervention strategies. By applying our model on MIT’s Stata center, we assess the impacts of three possible dimensions of intervention: one-way vs unrestricted movement, population size allowed onsite, and frequency of leaving designated work location for breaks. We find that there is no significant impact made by one-way movement restrictions over unrestricted movement. Instead, we find that reducing the frequency at which individuals leave their workstations combined with lowering the number of individuals admitted below the current recommendations lowers the likelihood of highly connected individuals within the contact networks that emerge, which in turn lowers the overall risk of infection. We discover three classes of possible interventions based on their epidemiological effects. By assuming a direct relationship between data on secondary attack rates and transmissibility in the agent-based SIR model, we compare relative infection risk of four respiratory illnesses, MERS, SARS, COVID-19, and Measles, within the simulated area, and recommend appropriate intervention guidelines.
Impact of temperature, inoculum flow pattern, inoculum type, and their ratio on dry anaerobic digestion for biogas production
Authors: Hossain Md Shahadat , Karim Tahmid ul , Onik Mahade Hassan , Kumar Deepak , Rahman Md Anisur , Yousuf Abu , Uddin Mohammad Rakib
Published: April 2022

This study is aimed to apply dry anaerobic digestion (DAD) for methane (CH4) enriched biogas production from unsorted organic municipal solid waste (MSW). Cumulative biogas production was monitored for 35 days of operation in batch digesters at fixed feedstock to inoculum (F/I) ratio 2. Anaerobic sludge (AS) and cow manure (CM) were used as inoculum in single and mixed modes. Several process parameters such as inoculum flow pattern (single layer, multilayer, and spiral), digestion temperature (25 to 40 °C), inoculation modes (single and mixed mode), and inoculation proportion (AS:CM = 1:1, 1:2, 1:3, and 2:1) were investigated to determine the optimum DAD conditions to maximize the CH4 laden biogas yield. The study of inoculum flow pattern showed that digester with multilayer inoculum configuration generated the maximum 555 mL cumulative biogas with the production rate of 195 mL/day (at 25 °C). Biogas production rate and cumulative biogas production were found to increase with a rise in temperature and the maximum values of 380 mL/day and 1515 mL respectively were observed at 37 °C. The mixed mode of inoculation containing AS and CM augmented the biogas yield at previously optimized conditions. Final results showed that digester with multilayer inoculum flow pattern at 37 °C produced 1850 mL cumulative biogas with 1256.58 mL CH4/kg volatile solid (VS) when the mixed inoculum was used at the AS:CM—1:2 ratio. Biogas production with this significant amount of CH4 justifies the use of the DAD process for energy (biogas) generation from widely available biomass feedstock (MSW), offering various advantages to the environment.
The relationship between stability of interpersonal coordination and inter-brain EEG synchronization during anti-phase tapping
Authors: Kurihara Yuto , Takahashi Toru , Osu Rieko
Published: April 2022

Inter-brain synchronization is enhanced when individuals perform rhythmic interpersonal coordination tasks, such as playing instruments in music ensembles. Experimentally, synchronization has been shown to correlate with the performance of joint tapping tasks. However, it is unclear whether inter-brain synchronization is related to the stability of interpersonal coordination represented as the standard deviation of relative phase (SDRP). In this study, we simultaneously recorded electroencephalograms of two paired individuals during anti-phase tapping in three interactive tapping conditions: slow (reference inter-tap interval [ITI]: 0.5 s), fast (reference ITI: 0.25 s), and free (preferred ITI), and pseudo tapping where each participant tapped according to the metronome sounds without interaction. We calculated the inter-brain synchronization between pairs of six regions of interest (ROI): frontal, central, left/right temporal, parietal, and occipital regions. During the fast tapping, the inter-brain synchronization significantly increased in multiple ROI pairs including temporoparietal junction in comparison to pseudo tapping. Synchronization between the central and left-temporal regions was positively correlated with SDRP in the theta in the fast condition. These results demonstrate that inter-brain synchronization occurs when task requirements are high and increases with the instability of the coordination.
Deep learning of chest X-rays can predict mechanical ventilation outcome in ICU-admitted COVID-19 patients
Authors: Gourdeau Daniel , Potvin Olivier , Biem Jason Henry , Cloutier Florence , Abrougui Lyna , Archambault Patrick , Chartrand-Lefebvre Carl , Dieumegarde Louis , Gagné Christian , Gagnon Louis , Giguère Raphaelle , Hains Alexandre , Le Huy , Lemieux Simon , Lévesque Marie-Hélène , Nepveu Simon , Rosenbloom Lorne , Tang An , Yang Issac , Duchesne Nathalie , Duchesne Simon
Published: April 2022

The COVID-19 pandemic repeatedly overwhelms healthcare systems capacity and forced the development and implementation of triage guidelines in ICU for scarce resources (e.g. mechanical ventilation). These guidelines were often based on known risk factors for COVID-19. It is proposed that image data, specifically bedside computed X-ray (CXR), provide additional predictive information on mortality following mechanical ventilation that can be incorporated in the guidelines. Deep transfer learning was used to extract convolutional features from a systematically collected, multi-institutional dataset of COVID-19 ICU patients. A model predicting outcome of mechanical ventilation (remission or mortality) was trained on the extracted features and compared to a model based on known, aggregated risk factors. The model reached a 0.702 area under the curve (95% CI 0.707-0.694) at predicting mechanical ventilation outcome from pre-intubation CXRs, higher than the risk factor model. Combining imaging data and risk factors increased model performance to 0.743 AUC (95% CI 0.746-0.732). Additionally, a post-hoc analysis showed an increase performance on high-quality than low-quality CXRs, suggesting that using only high-quality images would result in an even stronger model.
Uncovering the hydride ion diffusion pathway in barium hydride via neutron spectroscopy
Authors: Novak Eric , Daemen Luke , Ramirez-Cuesta Anibal Javier , Cheng Yongqiang , Smith Robert , Egami Takeshi , Jalarvo Niina
Published: April 2022

Solid state materials possessing the ability for fast ionic diffusion of hydrogen have immense appeal for a wide range of energy-related applications. Ionic hydrogen transport research is dominated by proton conductors, but recently a few examples of hydride ion conductors have been observed as well. Barium hydride, BaH2, undergoes a structural phase transition around 775 K that leads to an order of magnitude increase in the ionic conductivity. This material provides a prototypical system to understand hydride ion diffusion and how the altered structure produced by the phase transition can have an enormous impact on the diffusion. We employ quasielastic and inelastic neutron scattering to probe the atomic scale diffusion mechanism and vibrational dynamics of hydride ions in both the low- and high-temperature phases. Jump lengths, residence times, diffusion coefficients, and activation energies are extracted and compared to the crystal structure to uncover the diffusion pathways. We find that the hydrogen jump distances, residence times, and energy barriers become reduced following the phase transition, allowing for the efficient conduction of hydride ions through a series of hydrogen jumps of length L = 3.1 Å.
The association between institutional delivery and neonatal mortality based on the quality of maternal and newborn health system in India
Authors: Lee Hwa-Young , Leslie Hannah H. , Oh Juhwan , Kim Rockli , Kumar Alok , Subramanian S. V. , Kruk Margaret E.
Published: April 2022

Over 600,000 newborns in India died in their first month of life in 2017 despite large increases in access to maternal health services. We assess whether maternal and newborn health system quality in India is adequate for institutional delivery to reduce neonatal mortality. We identified recent births from the cross-sectional 2015–2016 National Family Health Survey and used reported content of antenatal care and immediate postpartum care averaged at the district level to characterize health system quality for maternity and newborn services. We used random effect logistic models to assess the relationship between institutional delivery and neonatal (death within the first 28 days of life) and early neonatal (death within 7 days of live births) mortality by quintile of district maternal and newborn health system quality. Three quarters of 191,963 births were in health facilities; 2% of newborns died within 28 days. District-level quality scores ranged from 40 to 90% of expected interventions. Institutional delivery was not protective against newborn mortality in the districts with poorest health system quality, but was associated with decreased mortality in districts with higher quality. Predicted neonatal mortality in the highest quintile of quality would be 0.018 (95% CI 0.010, 0.026) for home delivery and 0.010 (0.007, 0.013) for institutional delivery. Measurement of quality is limited by lack of data on quality of acute and referral care. Institutional delivery is associated with meaningful survival gains where quality of maternity services is higher. Addressing health system quality is an essential element of achieving the promise of increased access to maternal health services.
The appropriate and sequential value of standard radiograph, computed tomography and magnetic resonance imaging to characterize a bone tumor
Authors: Gaume M. , Chevret S. , Campagna R. , Larousserie F. , Biau D.
Published: April 2022

Radiographs (XR), computed tomography (CT) or magnetic resonance imaging (MRI) are regularly analyzed to determine whether a bone lesion is benign or malignant. An online quiz was created providing 15 cases with a clinical summary, MRI, CT, and XR. After each image, participants were asked to rate the probability (0–100%) the bone tumor was malignant. Order and difficulty of the images were randomly determined. Probability statements regarding the diagnosis were actualized along the sequence of exam, to quantify how the degree of belief changed to account for evidence from those exams. 64 physicians participated and provided 154 assessments from 1 (n = 18) to 3 (n = 44) different cases. After the first image, participants favored the correct malignancy status at 70%; 80% after the second and 80% after the third one. Participants were more likely to favor the correct malignancy status when the lesion was malignant and when first confronted with XR or CT, rather than MRI, though the most predictive factor of correct diagnosis was the difficulty of the case. In conclusion, the additional information provided by successive imaging studies was moderate. XR or CT seemed more appropriate than MRI as first imaging study. Bypassing XR should be discouraged.