bluuebunny/crossref_metadata_2025 huggingface dataset:
Phanerozoic Record of Northern Ellesmere Island, Canadian High Arctic, Resolved Through 40Ar/39Ar and (U‐Th)/He Geochronology
Authors: Powell Jeremy W. , Schneider David A.
Published: August 2022

The northern margin of Ellesmere Island, Canada, has experienced a complex geological history throughout the Phanerozoic, including multiple episodes of orogenesis and first‐order depositional cycles related to Circum‐Arctic evolution. Whereas previous studies have documented the structural and stratigraphic record of these events, supporting geochronological data are sparse. To constrain the age of these tectonic episodes, we apply 40Ar/39Ar geochronology and (U‐Th)/He low‐temperature thermochronology methods to polydeformed fault zones that bisect the Pearya terrane and Franklinian Basin of northern Ellesmere Island. Multiple single crystal 40Ar/39Ar dating of micas resulted in sample‐dependent date dispersion, with some samples exhibiting robust Paleozoic ages corresponding to the assembly and accretion of the Pearya terrane. Other samples yielded intra‐sample date dispersion that spanned the Late Paleozoic and Mesozoic, suggestive of a previously unreported post‐Ellesmerian and pre‐Eurekan history. Zircon and apatite (U‐Th)/He dates are largely Eocene in age, with dominant populations of c. 48 and c. 41 Ma, respectively. Inverse thermal history modeling of (U‐Th)/He data indicates episodic Mesozoic burial and unroofing coinciding with changes in the regional stress regime, and rapid cooling during nascent (>53 Ma) and initial (53–47 Ma) phases of Eurekan deformation. When integrated, our data provide temporal constraints on the timing of deformation, structural reactivation, and the Phanerozoic burial and erosive history of northern Ellesmere Island.
Shake, Rattle, and Probe
Authors: Benningfield Damond
Published: August 2022

Helioseismology allows scientists to study the interior of the Sun, solve some basic physics mysteries, and forecast space weather.
Eastern Mediterranean and Middle East Face Rapid Climate Change
Authors: Zittis George , Lelieveld Jos
Published: August 2022

Observational and modeling studies identify the Eastern Mediterranean and Middle East as a prominent climate change hotspot associated with weather extremes that have major impacts on society.
Future Changes of the Eddy Moisture Convergence in Winter Over Coastal Lands in Eastern North America and East Asia
Authors: Liang Wengui , Zhang Minghua
Published: August 2022

Previous studies have shown that increasing moisture convergence by transient eddies will cause winter precipitation increase in the future over the coastal lands in Eastern North America (ENA) and East Asia (EA). Using moisture budget and composite analyses, we investigate the physical processes responsible for the change of eddy moisture convergence and compare them between the two regions. We find that in addition to the “wet get wetter and dry get drier” (“WWDD”) thermodynamic effect, changes in eddy moisture advection cause enhanced eddy moisture convergence north of 30°N and divergence to the south, with magnitudes comparable to the “WWDD” effect in these regions. The north‐south dipole pattern is reflected in the precipitation change of drying over the southern coastal lands in the future climate. It is caused by enhanced downgradient eddy moisture transport in the north and upgradient eddy moisture transport in the south, which is explained by the locations of the maximum magnitude of eddy relative humidity in conjunction with increase of mean saturation specific humidity. The eddy dynamic intensities associated with extreme precipitation events are found to increase in the future, contributing to the increase of eddy moisture convergence, but it plays a secondary role. The strong similarities of the underlying processes of eddy moisture change between ENA and EA suggest robust response of the spatially varying role of eddies in impacting future change of regional precipitation in ENA and EA.
KLHL3 deficiency in mice ameliorates obesity, insulin resistance, and nonalcoholic fatty liver disease by regulating energy expenditure
Authors: Jang Ju-hong , Lee Jeong Woong , Cho Min Ji , Hwang Byungtae , Kwon Min-Gi , Kim Dong-Hwan , Lee Nam-Kyung , Lee Jangwook , Park Young-Jun , Yang Yong Ryoul , Kim Jinchul , Kim Yong-Hoon , An Tae Hyeon , Oh Kyoung-Jin , Bae Kwang-Hee , Park Jong-Gil , Min Jeong-Ki
Published: August 2022

Obesity is a growing global epidemic that can cause serious adverse health consequences, including insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). Obesity development can be attributed to energy imbalance and metabolic inflexibility. Here, we demonstrated that lack of Kelch-like protein 3 (KLHL3) mitigated the development of obesity, IR, and NAFLD by increasing energy expenditure. KLHL3 mutations in humans cause Gordon’s hypertension syndrome; however, the role of KLHL3 in obesity was previously unknown. We examined differences in obesity-related parameters between control and Klhl3−/− mice. A significant decrease in body weight concomitant with fat mass loss and improved IR and NAFLD were observed in Klhl3−/− mice fed a high-fat (HF) diet and aged. KLHL3 deficiency inhibited obesity, IR, and NAFLD by increasing energy expenditure with augmentation of O2 consumption and CO2 production. Delivering dominant-negative (DN) Klhl3 using adeno-associated virus into mice, thereby dominantly expressing DN-KLHL3 in the liver, ameliorated diet-induced obesity, IR, and NAFLD. Finally, adenoviral overexpression of DN-KLHL3, but not wild-type KLHL3, in hepatocytes revealed an energetic phenotype with an increase in the oxygen consumption rate. The present findings demonstrate a novel function of KLHL3 mutation in extrarenal tissues, such as the liver, and may provide a therapeutic target against obesity and obesity-related diseases.
Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults
Authors: Gui Yuanyuan , Zhou Xiaocheng , Wang Zixin , Zhang Yiliang , Wang Zhaobin , Zhou Geyu , Zhao Yize , Liu Manhua , Lu Hui , Zhao Hongyu
Published: August 2022

Although there are pronounced sex differences for psychiatric disorders, relatively little has been published on the heterogeneity of sex-specific genetic effects for these traits until very recently for adults. Much less is known about children because most psychiatric disorders will not manifest until later in life and existing studies for children on psychiatric traits such as cognitive functions are underpowered. We used results from publicly available genome-wide association studies for six psychiatric disorders and individual-level data from the Adolescent Brain Cognitive Development (ABCD) study and the UK Biobank (UKB) study to evaluate the associations between the predicted polygenic risk scores (PRS) of these six disorders and observed cognitive functions, behavioral and brain imaging traits. We further investigated the mediation effects of the brain structure and function, which showed heterogeneity between males and females on the correlation between genetic risk of schizophrenia and fluid intelligence. There was significant heterogeneity in genetic associations between the cognitive traits and psychiatric disorders between sexes. Specifically, the PRSs of schizophrenia of boys showed stronger correlation with eight of the ten cognitive functions in the ABCD data set; whereas the PRSs of autism of females showed a stronger correlation with fluid intelligence in the UKB data set. Besides cognitive traits, we also found significant sexual heterogeneity in genetic associations between psychiatric disorders and behavior and brain imaging. These results demonstrate the underlying early etiology of psychiatric disease and reveal a shared and unique genetic basis between the disorders and cognition traits involved in brain functions between the sexes.
SerpinE1 drives a cell-autonomous pathogenic signaling in Hutchinson–Gilford progeria syndrome
Authors: Catarinella Giorgia , Nicoletti Chiara , Bracaglia Andrea , Procopio Paola , Salvatori Illari , Taggi Marilena , Valle Cristiana , Ferri Alberto , Canipari Rita , Puri Pier Lorenzo , Latella Lucia
Published: August 2022

Hutchinson–Gilford progeria syndrome (HGPS) is a rare, fatal disease caused by Lamin A mutation, leading to altered nuclear architecture, loss of peripheral heterochromatin and deregulated gene expression. HGPS patients eventually die by coronary artery disease and cardiovascular alterations. Yet, how deregulated transcriptional networks at the cellular level impact on the systemic disease phenotype is currently unclear. A genome-wide analysis of gene expression in cultures of primary HGPS fibroblasts identified SerpinE1, also known as Plasminogen Activator Inhibitor (PAI-1), as central gene that propels a cell-autonomous pathogenic signaling from the altered nuclear lamina. Indeed, siRNA-mediated downregulation and pharmacological inhibition of SerpinE1 by TM5441 could revert key pathological features of HGPS in patient-derived fibroblasts, including re-activation of cell cycle progression, reduced DNA damage signaling, decreased expression of pro-fibrotic genes and recovery of mitochondrial defects. These effects were accompanied by the correction of nuclear abnormalities. These data point to SerpinE1 as a novel potential effector and target for therapeutic interventions in HGPS pathogenesis.
Autophagy-targeted nanoparticles for effective cancer treatment: advances and outlook
Authors: Long Xuehua , Yan Jianqin , Zhang Zhuoran , Chang Jing , He Bin , Sun Yong , Liang Yan
Published: August 2022

Autophagy enables the maintenance of nutrient recycling and metabolic homeostasis through a multistep lysosomal degradation pathway, and it has been demonstrated that autophagy can act as a tumor suppressor or tumor promoter, depending on the tumor microenvironment (TME). The dual role of autophagy in tumorigenesis results in two opposing therapeutic strategies, namely, inhibition versus promotion. However, due to the protective mechanisms of tumor cells and the absence of specific strategies for autophagy regulation, the modulation of autophagy has become a major consideration in cancer treatment. Owing to their unique properties, nanoparticles (NPs) have demonstrated excellent potential for overcoming these limitations. Here, we provide a summary of the latest progress in autophagy-targeting NPs for effective cancer treatment, and we conclude with recent advances in relevant clinical and preclinical studies. This summary of typical autophagy-targeted nano-drug delivery systems aims to provide references and expand ideas for researchers intending to explore this field. Finally, we provide an outlook on the potential of autophagy modulation in cancer treatment, and several key objective problems are carefully highlighted.
Efficient DNA fluorescence labeling via base excision trapping
Authors: Jun Yong Woong , Harcourt Emily M. , Xiao Lu , Wilson David L. , Kool Eric T.
Published: August 2022

Fluorescence labeling of DNAs is broadly useful, but methods for labeling are expensive and labor-intensive. Here we describe a general method for fluorescence labeling of oligonucleotides readily and cost-efficiently via base excision trapping (BETr), employing deaminated DNA bases to mark label positions, which are excised by base excision repair enzymes generating AP sites. Specially designed aminooxy-substituted rotor dyes trap the AP sites, yielding high emission intensities. BETr is orthogonal to DNA synthesis by polymerases, enabling multi-uracil incorporation into an amplicon and in situ BETr labeling without washing. BETr also enables labeling of dsDNA such as genomic DNA at a high labeling density in a single tube by use of nick translation. Use of two different deaminated bases facilitates two-color site-specific labeling. Use of a multi-labeled DNA construct as a bright fluorescence tag is demonstrated through the conjugation to an antibody for imaging proteins. Finally, double-strand selectivity of a repair enzyme is harnessed in sensitive reporting on the presence of a target DNA or RNA in a mixture with isothermal turnover and single nucleotide specificity. Overall, the results document a convenient and versatile method for general fluorescence labeling of DNAs.
High-surface-area corundum nanoparticles by resistive hotspot-induced phase transformation
Authors: Deng Bing , Advincula Paul A. , Luong Duy Xuan , Zhou Jingan , Zhang Boyu , Wang Zhe , McHugh Emily A. , Chen Jinhang , Carter Robert A. , Kittrell Carter , Lou Jun , Zhao Yuji , Yakobson Boris I. , Zhao Yufeng , Tour James M.
Published: August 2022

High-surface-area α-Al2O3 nanoparticles are used in high-strength ceramics and stable catalyst supports. The production of α-Al2O3 by phase transformation from γ-Al2O3 is hampered by a high activation energy barrier, which usually requires extended high-temperature annealing (~1500 K, > 10 h) and suffers from aggregation. Here, we report the synthesis of dehydrated α-Al2O3 nanoparticles (phase purity ~100%, particle size ~23 nm, surface area ~65 m2 g−1) by a pulsed direct current Joule heating of γ-Al2O3. The phase transformation is completed at a reduced bulk temperature and duration (~573 K, < 1 s) via an intermediate δʹ-Al2O3 phase. Numerical simulations reveal the resistive hotspot-induced local heating in the pulsed current process enables the rapid transformation. Theoretical calculations show the topotactic transition (from γ- to δʹ- to α-Al2O3) is driven by their surface energy differences. The α-Al2O3 nanoparticles are sintered to nanograined ceramics with hardness superior to commercial alumina and approaching that of sapphire.
The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation
Authors: Bai Xuemei , Sui Chao , Liu Feng , Chen Tian , Zhang Lei , Zheng Yi , Liu Bingyu , Gao Chengjiang
Published: August 2022

The signaling adaptor MAVS forms prion-like aggregates to activate the innate antiviral immune response after viral infection. However, spontaneous aggregation of MAVS can lead to autoimmune diseases. The molecular mechanism that prevents MAVS from spontaneous aggregation in resting cells has been enigmatic. Here we report that protein arginine methyltransferase 9 targets MAVS directly and catalyzes the arginine methylation of MAVS at the Arg41 and Arg43. In the resting state, this modification inhibits MAVS aggregation and autoactivation of MAVS. Upon virus infection, PRMT9 dissociates from the mitochondria, leading to the aggregation and activation of MAVS. Our study implicates a form of post-translational modification on MAVS, which can keep MAVS inactive in physiological conditions to maintain innate immune homeostasis.
DAXX-ATRX regulation of p53 chromatin binding and DNA damage response
Authors: Gulve Nitish , Su Chenhe , Deng Zhong , Soldan Samantha S. , Vladimirova Olga , Wickramasinghe Jayamanna , Zheng Hongwu , Kossenkov Andrew V. , Lieberman Paul. M.
Published: August 2022

DAXX and ATRX are tumor suppressor proteins that form a histone H3.3 chaperone complex and are frequently mutated in cancers with the alternative lengthening of telomeres (ALT). Here, we show that DAXX and ATRX knock-out (KO) U87-T cells that have acquired ALT-like features have defects in p53 chromatin binding and DNA damage response. RNA-seq analysis revealed that p53 pathway is among the most perturbed. ChIP-seq and ATAC-seq revealed a genome-wide reduction in p53 DNA-binding and corresponding loss of chromatin accessibility at many p53 response elements across the genome. Both DAXX and ATRX null cells showed a depletion of histone H3.3 and accumulation of γH2AX at many p53 sites, including subtelomeres. These findings indicate that loss of DAXX or ATRX can compromise p53 chromatin binding and p53 DNA damage response in ALT-like cells, providing a link between histone composition, chromatin accessibility and tumor suppressor function of p53.
Touchless interactive teaching of soft robots through flexible bimodal sensory interfaces
Authors: Liu Wenbo , Duo Youning , Liu Jiaqi , Yuan Feiyang , Li Lei , Li Luchen , Wang Gang , Chen Bohan , Wang Siqi , Yang Hui , Liu Yuchen , Mo Yanru , Wang Yun , Fang Bin , Sun Fuchun , Ding Xilun , Zhang Chi , Wen Li
Published: August 2022

In this paper, we propose a multimodal flexible sensory interface for interactively teaching soft robots to perform skilled locomotion using bare human hands. First, we develop a flexible bimodal smart skin (FBSS) based on triboelectric nanogenerator and liquid metal sensing that can perform simultaneous tactile and touchless sensing and distinguish these two modes in real time. With the FBSS, soft robots can react on their own to tactile and touchless stimuli. We then propose a distance control method that enabled humans to teach soft robots movements via bare hand-eye coordination. The results showed that participants can effectively teach a self-reacting soft continuum manipulator complex motions in three-dimensional space through a “shifting sensors and teaching” method within just a few minutes. The soft manipulator can repeat the human-taught motions and replay them at different speeds. Finally, we demonstrate that humans can easily teach the soft manipulator to complete specific tasks such as completing a pen-and-paper maze, taking a throat swab, and crossing a barrier to grasp an object. We envision that this user-friendly, non-programmable teaching method based on flexible multimodal sensory interfaces could broadly expand the domains in which humans interact with and utilize soft robots.
Directed evolution of phosphite dehydrogenase to cycle noncanonical redox cofactors via universal growth selection platform
Authors: Zhang Linyue , King Edward , Black William B. , Heckmann Christian M. , Wolder Allison , Cui Youtian , Nicklen Francis , Siegel Justin B. , Luo Ray , Paul Caroline E. , Li Han
Published: August 2022

Noncanonical redox cofactors are attractive low-cost alternatives to nicotinamide adenine dinucleotide (phosphate) (NAD(P)+) in biotransformation. However, engineering enzymes to utilize them is challenging. Here, we present a high-throughput directed evolution platform which couples cell growth to the in vivo cycling of a noncanonical cofactor, nicotinamide mononucleotide (NMN+). We achieve this by engineering the life-essential glutathione reductase in Escherichia coli to exclusively rely on the reduced NMN+ (NMNH). Using this system, we develop a phosphite dehydrogenase (PTDH) to cycle NMN+ with ~147-fold improved catalytic efficiency, which translates to an industrially viable total turnover number of ~45,000 in cell-free biotransformation without requiring high cofactor concentrations. Moreover, the PTDH variants also exhibit improved activity with another structurally deviant noncanonical cofactor, 1-benzylnicotinamide (BNA+), showcasing their broad applications. Structural modeling prediction reveals a general design principle where the mutations and the smaller, noncanonical cofactors together mimic the steric interactions of the larger, natural cofactors NAD(P)+.
Inequality can double the energy required to secure universal decent living
Authors: Millward-Hopkins Joel
Published: August 2022

Ecological breakdown and economic inequality are among the largest contemporary global challenges, and the issues are thoroughly entangled – as they have been throughout the history of civilisations. Yet, the global economy continues toward ecological crises, and inequalities remain far higher than citizens believe to be fair. Here, we explore the role of inequality, alongside traditional drivers of ecological impacts, in determining global energy requirements for providing universal decent living. We consider scenarios from fair inequality – where inequalities mirror public ideals – through a fairly unequal world, to one with a super-rich global elite. The energy-costs of inequality appear far more significant than population: even fair levels increase the energy required to provide universal decent living by 40%, and a super-rich global 1% could consume as much energy as would providing decent living to 1.7 billion. We finish by arguing that total population remains important nonetheless, but for reasons beyond ecological impacts.
Perforin-2 clockwise hand-over-hand pre-pore to pore transition mechanism
Authors: Jiao Fang , Dehez François , Ni Tao , Yu Xiulian , Dittman Jeremy S. , Gilbert Robert , Chipot Christophe , Scheuring Simon
Published: August 2022

Perforin-2 (PFN2, MPEG1) is a pore-forming protein that acts as a first line of defense in the mammalian immune system, rapidly killing engulfed microbes within the phagolysosome in macrophages. PFN2 self-assembles into hexadecameric pre-pore rings that transition upon acidification into pores damaging target cell membranes. Here, using high-speed atomic force microscopy (HS-AFM) imaging and line-scanning and molecular dynamics simulation, we elucidate PFN2 pre-pore to pore transition pathways and dynamics. Upon acidification, the pre-pore rings (pre-pore-I) display frequent, 1.8 s−1, ring-opening dynamics that eventually, 0.2 s−1, initiate transition into an intermediate, short-lived, ~75 ms, pre-pore-II state, inducing a clockwise pre-pore-I to pre-pore-II propagation. Concomitantly, the first pre-pore-II subunit, undergoes a major conformational change to the pore state that propagates also clockwise at a rate ~15 s−1. Thus, the pre-pore to pore transition is a clockwise hand-over-hand mechanism that is accomplished within ~1.3 s. Our findings suggest a clockwise mechanism of membrane insertion that with variations may be general for the MACPF/CDC superfamily.
Liquid-infused microstructured bioadhesives halt non-compressible hemorrhage
Authors: Bao Guangyu , Gao Qiman , Cau Massimo , Ali-Mohamad Nabil , Strong Mitchell , Jiang Shuaibing , Yang Zhen , Valiei Amin , Ma Zhenwei , Amabili Marco , Gao Zu-Hua , Mongeau Luc , Kastrup Christian , Li Jianyu
Published: August 2022

Non-compressible hemorrhage is an unmet clinical challenge that accounts for high mortality in trauma. Rapid pressurized blood flows under hemorrhage impair the function and integrity of hemostatic agents and the adhesion of bioadhesive sealants. Here, we report the design and performance of bioinspired microstructured bioadhesives, formed with a macroporous tough xerogel infused with functional liquids. The xerogel can rapidly absorb interfacial fluids such as whole blood and promote blood clotting, while the infused liquids facilitate interfacial bonding, sealing, and antibacterial function. Their synergy enables the bioadhesives to form tough adhesion on ex vivo human and porcine tissues and diverse engineered surfaces without the need for compression, as well as on-demand instant removal and storage stability. We demonstrate a significantly improved hemostatic efficacy and biocompatibility in rats and pigs compared to non-structured counterparts and commercial products. This work opens new avenues for the development of bioadhesives and hemostatic sealants.
Whole-exome analysis of 177 pediatric patients with undiagnosed diseases
Authors: Narita Kotaro , Muramatsu Hideki , Narumi Satoshi , Nakamura Yuji , Okuno Yusuke , Suzuki Kyogo , Hamada Motoharu , Yamaguchi Naoya , Suzuki Atsushi , Nishio Yosuke , Shiraki Anna , Yamamori Ayako , Tsumura Yusuke , Sawamura Fumi , Kawaguchi Masahiro , Wakamatsu Manabu , Kataoka Shinsuke , Kato Kohji , Asada Hideyuki , Kubota Tetsuo , Muramatsu Yukako , Kidokoro Hiroyuki , Natsume Jun , Mizuno Seiji , Nakata Tomohiko , Inagaki Hidehito , Ishihara Naoko , Yonekawa Takahiro , Okumura Akihisa , Ogi Tomoo , Kojima Seiji , Kaname Tadashi , Hasegawa Tomonobu , Saitoh Shinji , Takahashi Yoshiyuki
Published: August 2022

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24–35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.
Contactless doping characterization of $${\mathrm{Ga}_{2}\mathrm{O}_{3}}$$ using acceptor Cd probes
Authors: Barbosa Marcelo B. , Correia João Guilherme , Lorenz Katharina , Lopes Armandina M. L. , Oliveira Gonçalo N. P. , Fenta Abel S. , Schell Juliana , Teixeira Ricardo , Nogales Emilio , Méndez Bianchi , Stroppa Alessandro , Araújo João Pedro
Published: August 2022

Finding suitable p-type dopants, as well as reliable doping and characterization methods for the emerging wide bandgap semiconductor $$\beta$$
β
-$${\mathrm{Ga}_{2}\mathrm{O}_{3}}$$

Ga
2

O
3

could strongly influence and contribute to the development of the next generation of power electronics. In this work, we combine easily accessible ion implantation, diffusion and nuclear transmutation methods to properly incorporate the Cd dopant into the $$\beta$$
β
-$${\mathrm{Ga}_{2}\mathrm{O}_{3}}$$

Ga
2

O
3

lattice, being subsequently characterized at the atomic scale with the Perturbed Angular Correlation (PAC) technique and Density Functional Theory (DFT) simulations. The acceptor character of Cd in $$\beta$$
β
-$${\mathrm{Ga}_{2}\mathrm{O}_{3}}$$

Ga
2

O
3

is demonstrated, with Cd sitting in the octahedral Ga site having a negative charge state, showing no evidence of polaron deformations nor extra point defects nearby. The possibility to determine the charge state of Cd will allow assessing the doping type, in particular proving p-type character, without the need for ohmic contacts. Furthermore, a possible approach for contactless charge mobility studies is demonstrated, revealing thermally activated free electrons for temperatures above $$\sim$$
∼
648 K with an activation energy of 0.54(1) and local electron transport dominated by a tunneling process between defect levels and the Cd probes at lower temperatures.
Feasibility of low-cost particle sensor types in long-term indoor air pollution health studies after repeated calibration, 2019–2021
Authors: Anastasiou Elle , Vilcassim M. J. Ruzmyn , Adragna John , Gill Emily , Tovar Albert , Thorpe Lorna E. , Gordon Terry
Published: August 2022

Previous studies have explored using calibrated low-cost particulate matter (PM) sensors, but important research gaps remain regarding long-term performance and reliability. Evaluate longitudinal performance of low-cost particle sensors by measuring sensor performance changes over 2 years of use. 51 low-cost particle sensors (Airbeam 1 N = 29; Airbeam 2 N = 22) were calibrated four times over a 2-year timeframe between 2019 and 2021. Cigarette smoke-specific calibration curves for Airbeam 1 and 2 PM sensors were created by directly comparing simultaneous 1-min readings of a Thermo Scientific Personal DataRAM PDR-1500 unit with a 2.5 µm inlet. Inter-sensor variability in calibration coefficient was high, particularly in Airbeam 1 sensors at study initiation. Calibration coefficients for both sensor types trended downwards over time to < 1 at final calibration timepoint [Airbeam 1 Mean (SD) = 0.87 (0.20); Airbeam 2 Mean (SD) = 0.96 (0.27)]. We lost more Airbeam 1 sensors (N = 27 out of 56, failure rate 48.2%) than Airbeam 2 (N = 2 out of 24, failure rate 8.3%) due to electronics, battery, or data output issues. Evidence suggests degradation over time might depend more on particle sensor type, rather than individual usage. Repeated calibrations of low-cost particle sensors may increase confidence in reported PM levels in longitudinal indoor air pollution studies.
Phenome of coeliac disease vs. inflammatory bowel disease
Authors: Kleinjans Moritz , Schneider Carolin V. , Bruns Tony , Strnad Pavel
Published: August 2022

Coeliac disease (CeD) is characterized by gliadin-induced intestinal inflammation appearing in genetically susceptible individuals, such as HLA-DQ2.5 carriers. CeD, as well as other chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis, has been associated with increased morbidity and mortality, but the causes are unknown. We systematically analysed CeD-associated diagnoses and compared them to conditions enriched in subjects with CD/UC as well as in HLA-DQ2.5 carriers without CeD. We compared the overall and cause-specific mortality and morbidity of 3,001 patients with CeD, 2,020 with CD, 4,399 with UC and 492,200 controls in the community-based UK Biobank. Disease-specific phenotypes were assessed with the multivariable Phenome Wide Association Study (PheWAS) method. Associations were adjusted for age, sex and body mass index. All disease groups displayed higher overall mortality than controls (CD: aHR = 1.91[1.70–2.17]; UC: aHR = 1.32 [1.20–1.46]; CeD: aHR = 1.38 [1.22–1.55]). Cardiovascular and cancer-related deaths were responsible for the majority of fatalities. PheWAS analysis revealed 166 Phecodes overrepresented in all three disorders, whereas only ~ 20% of enriched Phecodes were disease specific. Seven of the 58 identified CeD-specific Phecodes were enriched in individuals homozygous for HLA-DQ2.5 without diagnosed CeD. Four out of these seven Phecodes and eight out of 19 HLA-DQ2.5 specific Phecodes were more common in homozygous HLA-DQ2.5 subjects with vs. without CeD, highlighting the interplay between genetics and diagnosis-related factors. Our study illustrates that the morbidity and mortality in CeD share similarities with CD/UC, while the CeD-restricted conditions might be driven by both inherited and acquired factors.
Quality and timeliness of emergency obstetric care and its association with maternal outcome in Keren Hospital, Eritrea
Authors: Zewde Henos Kiflom
Published: August 2022

Despite the critical role quality comprehensive emergency obstetric care (CEmOC) plays in ensuring safe motherhood, only a few studies have attempted to measure the impact of substandard and delayed care on maternal outcome thus far. This study evaluates the association between various process and timeliness indicators of CEmOC and adverse maternal outcome in Keren Hospital. This study compared women with potentially life-threatening condition (PLTC) and women with severe maternal outcome (SMO) with respect to various process and timeliness indicators. Logistic regression analysis was employed to assess the association of timeliness and process indicators with SMO using SPSS version-22 computer software. In this study, we included 491 cases of PLTC and 210 cases of SMO (171 maternal near misses and 39 maternal deaths). The following process indicators showed significant association with SMO: failure to give uterotonics for the treatment of postpartum hemorrhage, failure to administer prophylactic antibiotics, and delayed laporatomy for uterine rupture. Moreover, delays in referral, triaging, seeing an obstetrician, and receiving definitive treatement were strongly associated with SMO. The following causes of delay were also found to be independently associated with SMO: erroneous diagnosis, inappropriate management, multiple referrals between health facilities, unavailability of a senior obstetrician, and poor communication during referral. Among the miscellaneous factors, nighttime admission and referral during the rainy season showed significant association with SMO. Findings of this study indicate that huge gap exists in providing quality and timely care in Keren Hospital. In general, most incidents of substandard and delayed care were due to poor referral system, insufficiency of medical staff, inadequacy of drugs and equipment, and unavailability of standard management protocol. Improving the referral system, upgrading the technical skills of health professionals, making sure life-saving drugs and equipment are available all the time, and posting standard treatment and management protocols in the maternity and emergency rooms will play a vital role in reducing the occurrence of SMO in Keren Hospital.
Relationship between serum 25 hydroxyvitamin D (25(OH)D) levels and mental health in shift female nurses
Authors: Tang Hsin-Ya , Ko Wang-Sheng , Yan Yuan-Horng , Yu Su-Chen , Chiou Ya-ling
Published: August 2022

The nurses work long hours and in various shifts, and often accompanied by depression, fatigue, and sleep disorders. Many studies have found that 25 hydroxyvitamin D (25(OH)D) is related to mental health. We aimed to investigate the relationship between depression, sleep problems, fatigue, and serum 25(OH)D levels in shift nurses. We recruited 34 day-shift, 30 evening-shift and 31 night-shift nurses. The Beck Depression Inventory II (BDI-II), Numerical Rating Scale and General Sleep Disturbance Scale to evaluate the levels of depression, sleep problems, fatigue. Blood samples (20 ml) were collected under a fasting state to determine basic biochemistry and inflammatory parameters. In central of Taiwan, approximately 96.1% of shift nurses had deficient (< 20 ng/ml) (45 females and 1 male) and inadequate (20–29 ng/ml) (39 females and 2 male) 25(OH)D levels. Approximately 84.2% of shift nurses experienced fatigue. In sleep disturbance, night-shift nurses experienced significantly more severe sleep disturbance than day-shift and evening-shift nurses. However, no significant correlation was observed between 25(OH)D levels and mental health when the 25(OH)D level was categorized. 25(OH)D deficiency, sleep disturbance, depression, and fatigue were common in shift female nurses, but it was not possible to demonstrate the impact of 25(OH)D deficiency on the mental health of shift nurses in Taiwan.
Experimental characterization of $${\text {H}}_2$$/water multiphase flow in heterogeneous sandstone rock at the core scale relevant for underground hydrogen storage (UHS)
Authors: Boon Maartje , Hajibeygi Hadi
Published: August 2022

Geological porous reservoirs provide the volume capacity needed for large scale underground hydrogen storage (UHS). To effectively exploit these reservoirs for UHS, it is crucial to characterize the hydrogen transport properties inside porous rocks. In this work, for the first time in the community, we have performed $${\text {H}}_2$$

H
2

/water multiphase flow experiments at core scale under medical X-ray CT scanner. This has allowed us to directly image the complex transport properties of $${\text {H}}_2$$

H
2

when it is injected or retracted from the porous rock. The important effective functions of capillary pressure and relative permeability are also measured, for both drainage and imbibition. The capillary pressure measurements are combined with MICP data to derive a receding contact angle for the $${\text {H}}_2$$

H
2

/water/sandstone rock system. The rock core sample is a heterogeneous Berea sandstone (17 cm long and 3.8 cm diameter). Our investigation reveals the interplay between gravitational, capillary, and viscous forces. More specifically, it illustrates complex displacement patterns in the rock, including gravity segregation, enhancement of spreading of $${\text {H}}_2$$

H
2

due to capillary barriers, and the formation of fingers/channel during imbibition which lead to significant trapping of hydrogen. These findings shed new light on our fundamental understanding of the transport characteristics of $${\text {H}}_2$$

H
2

/water relevant for UHS.
Distance-based paper device using combined SYBR safe and gold nanoparticle probe LAMP assay to detect Leishmania among patients with HIV
Authors: Ruang-areerate Toon , Saengsawang Natkrittaya , Ruang-areerate Panthita , Ratnarathorn Nalin , Thita Thanyapit , Leelayoova Saovanee , Siripattanapipong Suradej , Choowongkomon Kiattawee , Dungchai Wijitar
Published: August 2022

Asymptomatic visceral leishmaniasis cases increase continuously, particularly among patients with HIV who are at risk to develop further symptoms of leishmaniasis. A simple, sensitive and reliable diagnosis is crucially needed due to risk populations mostly residing in rural communities with limited resources of laboratory equipment. In this study, a highly sensitive and selective determination of Leishmania among asymptomatic patients with Leishmania/HIV co-infection was achieved to simultaneously interpret and semi-quantify using colorimetric precipitates (gold-nanoparticle probe; AuNP-probe) and fluorescence (SYBR safe dye and distance-based paper device; dPAD) in one-step loop-mediated isothermal amplification (LAMP) assay. The sensitivities and specificities of 3 detection methods were equivalent and had reliable performances achieving as high as 95.5%. Detection limits were 102 parasites/mL (0.0147 ng/µL) which were 10 times more sensitive than other related studies. To empower leishmaniasis surveillance as well as prevention and control, this dPAD combined with SYBR safe and gold nanoparticle probe LAMP assay is reliably fast, simple, inexpensive and practical for field diagnostics to point-of-care settings in resource-limited areas which can be set up in all levels of healthcare facilities, especially in low to middle income countries.
Using of geographic information systems (GIS) to determine the suitable site for collecting agricultural residues
Authors: Khater El-Sayed G. , Ali Samir A. , Afify Mohamed T. , Bayomy Magdy A. , Abbas Rasha S.
Published: August 2022

The main aim of this study is to use the Geographic Information Systems (GIS) techniques to determine the optimum site to collect the residues in order to reduce cost and increase the benefits. To achieve these three scenarios were studied to reach the best collection sites for recycling rice straw in Sinbilawin center. The results indicate that the first scenario: The result was forty (40) collection sites in this status the cost of transfer will be very high because the collecting starts from inside village to the 40 sites and transfer to main sites to recycle operation. The second scenario: The total lengths of roads are not much then the cost of transfer is low and save time and efforts. The third scenario: The result was five collecting sites. It was shortest length and lowest cost. Transportation costs in the first scenario were difficult to calculate because of the difficulty to access a network of documented roads from satellite maps to use it with the GIS program. The total internal transport costs were 987,308.86 and 826,966.43 L.E (Egyptian pound, $ = 19.15 L.E) for second and third scenarios, respectively. The average transport costs per ton were 17 and 14 L.E/ton for the second and third scenarios, respectively. Also, the total lengths of roads were 817.62 and 615.65 km for the second and third scenarios, respectively.
Efficacy, safety and prognostic factors in patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil plus bevacizumab in a real-world setting
Authors: Martínez-Lago Nieves , Chucla Teresa Calleja , De Castro Beatriz Alonso , Ponte Rafael Varela , Rendo Cristina Reboredo , Rodriguez Martin Igor Gomez-Randulfe , Diaz Sofia Silva , Suarez Begoña Graña , de la Cámara Gomez Juan , Fernández Fernando Busto , Salvador María Mateos , Lopez Margarita Reboredo
Published: August 2022

We evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab in treating refractory metastatic colorectal cancer (mCRC) in a retrospective, observational study. Patients refractory or intolerant to standard therapies received TAS-102 (30–35 mg/m2 twice daily on days 1–5 and days 8–12 every 28 days) plus bevacizumab 5 mg/kg on days 1 and 15. Clinical and pathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) data were collected and analysed. Thirty-five patients were treated from July 2019 to October 2021 (median age 64 years). The majority of patients (68.6%) were receiving TAS-102 plus bevacizumab as third-line treatment. Patients received a median of 4 (range 2–15) cycles of treatment. Among 31 patients evaluable for response (88.6%), ORR and DCR were 3.2% and 51.6%, respectively. After a median 11.6 months’ follow-up, median PFS was 4.3 (95% confidence interval [CI] 3.4–5.1) months and median OS was 9.3 (95% CI 6.6–12.1) months. The most common grade 3–4 toxicities were neutropenia, asthenia and nausea/vomiting, and there were no treatment-related deaths. This real-world study confirms the efficacy and safety of TAS-102 plus bevacizumab in patients with refractory mCRC.
The benefit of anti-angiogenic therapy in EGFR exon 21 L858R mutant non-small cell lung cancer patients: a retrospective study
Authors: You Liangkun , Zheng Xinnan , Deng Danchen , Pan Hongming , Han Weidong
Published: August 2022

Patients with epidermal growth factor receptor (EGFR) exon 21 L858R substitution benefit less from standard EGFR tyrosine kinase inhibitor (TKI) treatment, and whether anti-angiogenic therapy was beneficial to the EGFR L858R subpopulation was inconclusive. A retrospective study was conducted to investigate the survival benefit and the target characteristics of the anti-angiogenic agent in the EGFR L858R patients in our center, comparing those treated with or without anti-angiogenic therapy (cohort A and cohort B). At the median follow-up time of 31.0 months vs 32.7 months (cohort A vs. B) respectively, Cohort A (n = 58) had a significantly prolonged median OS compared to Cohort B (n = 101) (60.0 months vs.37.0 months, HR 0.51, p = 0.016). Anti-angiogenic therapy significantly prolonged the OS in patients with liver metastases (NA vs.26.0 months, HR 0.17, p = 0.023) comparing to patients without liver metastases (60.0 months vs.37.0 months, HR 0.63, p = 0.129). For brain metastatic patients, anti-angiogenic treatment tended to improve median OS with (65.0 months vs.35.0 months, HR 0.29, p = 0.068) or without brain radiotherapy (73.0 months vs.29.0 months, HR 0.24, p = 0.171). The grade 3 or more adverse events were manageable and consistent with previous studies. Patients with EGFR L858R mutation treated with anti-angiogenic therapy in their course of treatment had a significantly prolonged OS compared to those who had never received an anti-angiogenic agent. Patients with liver metastases might benefit more from anti-angiogenic therapy than those without.
UDP-glucose, cereblon-dependent proinsulin degrader
Authors: Cho Jaeyong , Miyagawa Atsushi , Yamaguchi Kazuki , Abe Wakana , Tsugawa Yoji , Yamamura Hatsuo , Imai Takeshi
Published: August 2022

Insulin secretion is regulated in multiple steps, and one of the main steps is in the endoplasmic reticulum (ER). Here, we show that UDP-glucose induces proinsulin ubiquitination by cereblon, and uridine binds and competes for proinsulin degradation and behaves as sustainable insulin secretagogue. Using insulin mutagenesis of neonatal diabetes variant-C43G and maturity-onset diabetes of the young 10 (MODY10) variant-R46Q, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) protects cereblon-dependent proinsulin ubiquitination in the ER. Cereblon is a ligand-inducible E3 ubiquitin ligase, and we found that UDP-glucose is the first identified endogenous proinsulin protein degrader. Uridine-containing compounds, such as uridine, UMP, UTP, and UDP-galactose, inhibit cereblon-dependent proinsulin degradation and stimulate insulin secretion from 3 to 24 h after administration in β-cell lines as well as mice. This late and long-term insulin secretion stimulation is designated a day sustainable insulin secretion stimulation. Uridine-containing compounds are designated as proinsulin degradation regulators.
External validation of the hospital frailty risk score among older adults receiving mechanical ventilation
Authors: Sy Eric , Kassir Sandy , Mailman Jonathan F. , Sy Sarah L.
Published: August 2022

To externally validate the Hospital Frailty Risk Score (HFRS) in critically ill patients. We selected older adult (≥ 75 years old) hospitalizations receiving mechanical ventilation, using the Nationwide Readmissions Database (January 1, 2016-November 30, 2018). Frailty risk was subcategorized into low-risk (HFRS score < 5), intermediate-risk (score 5–15), and high-risk (score > 15). We evaluated the HFRS to predict in-hospital mortality, prolonged hospitalization, and 30-day readmissions, using multivariable logistic regression, adjusting for patient and hospital characteristics. Model performance was assessed using the c-statistic, Brier score, and calibration plots. Among 649,330 weighted hospitalizations, 9.5%, 68.3%, and 22.2% were subcategorized as low-, intermediate-, and high-risk for frailty, respectively. After adjustment, high-risk patient hospitalizations were associated with increased risks of prolonged hospitalization (adjusted odds ratio [aOR] 5.59 [95% confidence interval [CI] 5.24–5.97], c-statistic 0.694, Brier 0.216) and 30-day readmissions (aOR 1.20 [95% CI 1.13–1.27], c-statistic 0.595, Brier 0.162), compared to low-risk hospitalizations. Conversely, high-risk hospitalizations were inversely associated with in-hospital mortality (aOR 0.46 [95% CI 0.45–0.48], c-statistic 0.712, Brier 0.214). The HFRS was not successfully validated to predict in-hospital mortality in critically ill older adults. While it may predict other outcomes, its use should be avoided in the critically ill.
Calcium and phosphorus supplemented diet increases bone volume after thirty days of high speed treadmill exercise in adult mice
Authors: Friedman Michael A. , Kohn David H.
Published: August 2022

Weight-bearing exercise increases bone mass and strength. Increasing bone loading frequency during exercise can strengthen bone. Combining exercise with a calcium- and phosphorus-supplemented diet increases cortical area more than exercise alone in mice. Thus, we hypothesized that combining high-speed treadmill exercise while feeding mice a mineral-supplemented diet would lead to greater cortical area than high-speed exercise on a standard diet and low-speed exercise on a supplemented diet. Fifteen-week old male C57BL/6 mice were assigned to seven groups—(1) baseline, (2) non-exercise fed a control diet, (3) non-exercise fed a supplemented diet, (4) low-speed exercise fed a control diet, (5) low-speed exercise fed a supplemented diet, (6) high-speed exercise fed a control diet, and (7) high-speed exercise fed a supplemented diet. Mice exercised thirty days for 20 min/day at 12 m/min or 20 m/min. Tibiae were assessed by micro-CT and 4-point bending. Cortical area fraction and trabecular bone volume fraction (BV/TV) were significantly increased by the supplemented diet. High-speed exercised mice had significantly lower body weight, with no detrimental effects to bone health. Increasing running speed can decrease body weight while maintaining the benefits of exercise and nutrition on bone health. Running can lower body weight without harming bone health.
Development and characterisation of cysteine-based gold electrodes for the electrochemical biosensing of the SARS-CoV-2 spike antigen
Authors: Olgaç Nursel , Şahin Yücel , Liv Lokman
Published: August 2022

Cysteine-based two novel biosensing platforms were used for determining the SARS-CoV-2 spike antigen protein in spiked-saliva and clinical samples.
Development of a paper-based lateral flow prothrombin assay
Authors: Saidykhan Jerro , Pointon Louise , Cinti Stefano , May Jennifer E. , Killard Anthony J.
Published: August 2022

Devices fabricated using chromatography paper and wax printing, modified with thromboplastin (top left). Distance travelled by plasma samples (bottom right) is proportional to hospital prothrombin time (PT) (main graph) from normal (green) to significantly prolonged (red).