bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights Into NOx and HONO Chemistry in the Tropical Marine Boundary Layer at Cape Verde During the MarParCloud Campaign
Authors: Jiang Ying , Hoffmann Erik H. , Tilgner Andreas , Aiyuk Marvel B. E. , Andersen Simone T. , Wen Liang , van Pinxteren Manuela , Shen Hengqing , Xue Likun , Wang Wenxing , Herrmann Hartmut
Published: August 2023

Chemical processing of reactive nitrogen species, especially of NOx (= NO + NO2) and nitrous acid (HONO), determines the photochemical ozone production and oxidation capacity in the troposphere. However, sources of HONO and NOx in the remote marine atmosphere are still poorly understood. In this work, the multiphase chemistry mechanism CAPRAM in the model framework SPACCIM was used to study HONO formation at Cape Verde (CVAO) in October 2017, adopted with the input of current parameterizations for various HONO sources. Three simulations were performed that adequately reproduced ambient HONO levels and its diurnal pattern. The model performance for NOx and O3 improves significantly when considering dust‐surface‐photocatalytic conversions of reactive nitrogen compounds with high correlation coefficients up to 0.93, 0.56, and 0.89 for NO, NO2, and O3, respectively. Photocatalytic conversion of the adsorbed HNO3 on dust is modeled to be the predominant contributor for daytime HONO at CVAO, that is, accounting for about 62% of the chemical formation rate at noontime. In contrast, the ocean‐surface‐mediated conversion of NO2 to HONO and other discussed pathways are less important. The average OH levels at midday (9:00–16:00) modeled for cluster trajectory 1, 2, and 3 are 5.2, 5.1, and 5.2 × 106 molecules cm−3, respectively. Main OH formation is driven by O3 photolysis with a contribution of 74.6% to the total source rate, while HONO photolysis is negligible (∼1.8%). In summary, this study highlights the key role of dust aerosols for HONO formation and NOx cycling at CVAO and possibly in other dust‐affected regions, urgently calling for further investigations using field and model studies.
Glasdegib plus intensive or non-intensive chemotherapy for untreated acute myeloid leukemia: results from the randomized, phase 3 BRIGHT AML 1019 trial
Authors: Sekeres Mikkael A. , Montesinos Pau , Novak Jan , Wang Jianxiang , Jeyakumar Deepa , Tomlinson Benjamin , Mayer Jiri , Jou Erin , Robak Tadeusz , Taussig David C. , Dombret Hervé , Merchant Akil , Shaik Naveed , O’Brien Thomas , Roh Whijae , Liu Xueli , Ma Wendy , DiRienzo Christine G. , Chan Geoffrey , Cortes Jorge E.
Published: August 2023

This is the primary report of the randomized, placebo-controlled phase 3 BRIGHT AML 1019 clinical trial of glasdegib in combination with intensive chemotherapy (cytarabine and daunorubicin) or non-intensive chemotherapy (azacitidine) in patients with untreated acute myeloid leukemia. Overall survival (primary endpoint) was similar between the glasdegib and placebo arms in the intensive (n = 404; hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.782–1.408; two-sided p = 0.749) and non-intensive (n = 325; HR 0.99; 95% CI: 0.768–1.289; two-sided p = 0.969) studies. The proportion of patients who experienced treatment-emergent adverse events was similar for glasdegib versus placebo (intensive: 99.0% vs. 98.5%; non-intensive: 99.4% vs. 98.8%). The most common treatment-emergent adverse events were nausea, febrile neutropenia, and anemia in the intensive study and anemia, constipation, and nausea in the non-intensive study. The addition of glasdegib to either cytarabine and daunorubicin or azacitidine did not significantly improve overall survival and the primary efficacy endpoint for the BRIGHT AML 1019 phase 3 trial was not met. Clinical trial registration: ClinicalTrials.gov: NCT03416179.
Double-antibody-based nano-biosensing system for the onsite monitoring of SARS-CoV-2 variants
Authors: Hussein Heba A. , Kandeil Ahmed , Gomaa Mokhtar , Hassan Rabeay Y. A.
Published: August 2023

The fast and reliable diagnosis of COVID-19 is the foremost priority for promoting public health interventions. Therefore, double-antibody-based immunobiosensor chips were designed, constructed, and exploited for clinical diagnosis. Gold nanoparticles/tungsten oxide/carbon nanotubes (AuNPs/WO3/CNTs) were used as the active working sensor surface to support the chemical immobilization of a mixture of SARS-CoV-2 antibodies (anti-RBD-S and anti-RBD-S-anti-Llama monoclonal antibodies). The morphology and chemical functionalization of the fabricated disposable immunochips was characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). After full assay optimization, the immunobiosensor showed a high sensitivity to detect SARS-CoV-2-S protein with limits of detection and quantification of 1.8 and 5.6 pg/mL, respectively. On the other hand, for the SARS-CoV-2 whole virus particle analysis, the detection and quantification limits were determined to be 5.7 and 17 pg/mL, respectively. The biosensor showed a highly selective response toward SARS-CoV-2, even in the presence of influenza, nontargeting human coronaviruses, and Middle East respiratory syndrome coronavirus (MERS-CoV). The immunochips exhibited distinct responses toward the variants of concern: B.1>C.36.3>Omicron> Delta> Alpha coronavirus variants. For biosensor validation, twenty-nine clinical specimens were analyzed, and the impedimetric responses were positively detected for two Delta samples, eighteen Omicron samples, and six B.1-type samples in addition to three negative samples. Eventually, the immunobiosensor was fabricated in the form of ready-to-use chips capable of sensitive detection of virus variants, especially variants of concern (VOC) and interest, in a specimen within 15 min. The chips provided instantaneous detection with the direct application of clinical samples and are considered a point-of-care device that could be used in public places and hot spots.
Methylotrophic methanogens and bacteria synergistically demethylate dimethylarsenate in paddy soil and alleviate rice straighthead disease
Authors: Chen Chuan , Li Lingyan , Wang Yanfen , Dong Xiuzhu , Zhao Fang-Jie
Published: August 2023

Microorganisms play a key role in arsenic (As) biogeochemistry, transforming As species between inorganic and organic forms and different oxidation states. Microbial As methylation is enhanced in anoxic paddy soil, producing primarily dimethylarsenic (DMAs), which can cause rice straighthead disease and large yield losses. DMAs can also be demethylated in paddy soil, but the microorganisms driving this process remain unclear. In this study, we showed that the enrichment culture of methylotrophic methanogens from paddy soil demethylated pentavalent DMAs(V) efficiently. DMAs(V) was reduced to DMAs(III) before demethylation. 16S rRNA gene diversity and metagenomic analysis showed that Methanomassiliicoccus dominated in the enrichment culture, with Methanosarcina and Methanoculleus also being present. We isolated Methanomassiliicoccus luminyensis CZDD1 and Methanosarcina mazei CZ1 from the enrichment culture; the former could partially demethylate trivalent DMAs(III) but not DMAs(V) and the latter could demethylate neither. Addition of strain CZDD1 to the enrichment culture greatly accelerated DMAs(V) demethylation. Demethylation of DMAs(V) in the enrichment culture was suppressed by ampicillin, suggesting the involvement of bacteria. We isolated three anaerobic bacterial strains including Clostridium from the enrichment culture, which could produce hydrogen and reduce DMAs(V) to DMAs(III). Furthermore, augmentation of the Methanomassiliicoccus-Clostridium coculture to a paddy soil decreased DMAs accumulation by rice and alleviated straighthead disease. The results reveal a synergistic relationship whereby anaerobic bacteria reduce DMAs(V) to DMAs(III) for demethylation by Methanomassiliicoccus and also produce hydrogen to promote the growth of Methanomassiliicoccus; enhancing their populations in paddy soil can help alleviate rice straighthead disease.
Brain mediators of negative affect-induced physical symptom reporting in patients with functional somatic syndromes
Authors: Bogaerts Katleen , Van Den Houte Maaike , Jongen Daniëlle , Ly Huynh Giao , Coppens Eline , Schruers Koen , Van Diest Ilse , Jan Tack , Van Wambeke Peter , Petre Bogdan , Kragel Philip A. , Lindquist Martin A. , Wager Tor D. , Van Oudenhove Lukas , Van den Bergh Omer
Published: August 2023

Functional somatic syndromes (FSS) include fibromyalgia, irritable bowel syndrome (IBS), and others. In FSS patients, merely viewing negative affective pictures can elicit increased physical symptoms. Our aim was to investigate the neural mechanisms underlying such negative affect-induced physical symptoms in FSS patients. Thirty patients with fibromyalgia and/or IBS and 30 healthy controls (all women) watched neutral, positive and negative affective picture blocks during functional MRI scanning and rated negative affect and physical symptoms after every block. We compared brain-wide activation during negative versus neutral picture viewing in FSS patients versus controls using robust general linear model analysis. Further, we compared neurologic pain signature (NPS), stimulus intensity-independent pain signature (SIIPS) and picture-induced negative emotion signature (PINES) responses to the negative versus neutral affect contrast and investigated whether they mediated between-group differences in affective picture-induced physical symptom reporting. More physical symptoms were reported after viewing negative compared to neutral pictures, and this effect was larger in patients than controls (p = 0.025). Accordingly, patients showed stronger activation in somatosensory regions during negative versus neutral picture viewing. NPS, but not SIIPS nor PINES, responses were higher in patients than controls during negative versus neutral pictures (p = 0.026). These differential NPS responses partially mediated between-group differences in physical symptoms. In conclusion, picture-induced negative affect elicits physical symptoms in FSS patients as a result of activation of somatosensory and nociceptive brain patterns, supporting the idea that affect-driven alterations in processing of somatic signals is a critical mechanism underlying FSS.
Knockdown of SETD2 promotes erastin-induced ferroptosis in ccRCC
Authors: Xue Wei , Jian Wengang , Meng Yuyang , Wang Tengda , Cai Licheng , Yu Yongchun , Yu Yipeng , Xia Zhinan , Zhang Cheng
Published: August 2023

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is associated with poor prognosis. The histone H3 lysine 36 methyltransferase SET-domain-containing 2 (SETD2) has been reported to be expressed at low levels and frequently mutated in ccRCC. Ferroptosis, a form of death distinct from apoptosis and necrosis, has been reported in recent years in renal cancer. However, the relationship between SETD2 and ferroptosis in renal cancer is not clear. Here, we demonstrated that SETD2 was expressed at low levels in ccRCC and was associated with poor prognosis. Moreover, we found that knockdown of SETD2 increased lipid peroxidation and Fe2+ levels in tumor cells, thereby increasing the sensitivity of erastin, a ferroptosis inducer. Mechanistically, histone H3 lysine 36 trimethylation (H3K36me3) which was catalyzed by SETD2, interacted with the promoter of ferrochelatase (FECH) to regulate its transcription and ferroptosis-related signaling pathways. In conclusion, the presesnt study revealed that knockdown of the epigenetic molecule, SETD2, significantly increases the sensitivity of ferroptosis inducers which promotes tumor cell death, thereby indicating that SETD2 may be a potential therapeutic target for ccRCC.
Erythropoietin re-wires cognition-associated transcriptional networks
Authors: Singh Manvendra , Zhao Ying , Gastaldi Vinicius Daguano , Wojcik Sonja M. , Curto Yasmina , Kawaguchi Riki , Merino Ricardo M. , Garcia-Agudo Laura Fernandez , Taschenberger Holger , Brose Nils , Geschwind Daniel , Nave Klaus-Armin , Ehrenreich Hannelore
Published: August 2023

Recombinant human erythropoietin (rhEPO) has potent procognitive effects, likely hematopoiesis-independent, but underlying mechanisms and physiological role of brain-expressed EPO remained obscure. Here, we provide transcriptional hippocampal profiling of male mice treated with rhEPO. Based on ~108,000 single nuclei, we unmask multiple pyramidal lineages with their comprehensive molecular signatures. By temporal profiling and gene regulatory analysis, we build developmental trajectory of CA1 pyramidal neurons derived from multiple predecessor lineages and elucidate gene regulatory networks underlying their fate determination. With EPO as ‘tool’, we discover populations of newly differentiating pyramidal neurons, overpopulating to ~200% upon rhEPO with upregulation of genes crucial for neurodifferentiation, dendrite growth, synaptogenesis, memory formation, and cognition. Using a Cre-based approach to visually distinguish pre-existing from newly formed pyramidal neurons for patch-clamp recordings, we learn that rhEPO treatment differentially affects excitatory and inhibitory inputs. Our findings provide mechanistic insight into how EPO modulates neuronal functions and networks.
Linking emotional valence and anxiety in a mouse insula-amygdala circuit
Authors: Nicolas C. , Ju A. , Wu Y. , Eldirdiri H. , Delcasso S. , Couderc Y. , Fornari C. , Mitra A. , Supiot L. , Vérité A. , Masson M. , Rodriguez-Rozada S. , Jacky D. , Wiegert J. S. , Beyeler A.
Published: August 2023

Responses of the insular cortex (IC) and amygdala to stimuli of positive and negative valence are altered in patients with anxiety disorders. However, neural coding of both anxiety and valence by IC neurons remains unknown. Using fiber photometry recordings in mice, we uncover a selective increase of activity in IC projection neurons of the anterior (aIC), but not posterior (pIC) section, when animals are exploring anxiogenic spaces, and this activity is proportional to the level of anxiety of mice. Neurons in aIC also respond to stimuli of positive and negative valence, and the strength of response to strong negative stimuli is proportional to mice levels of anxiety. Using ex vivo electrophysiology, we characterized the IC connection to the basolateral amygdala (BLA), and employed projection-specific optogenetics to reveal anxiogenic properties of aIC-BLA neurons. Finally, we identified that aIC-BLA neurons are activated in anxiogenic spaces, as well as in response to aversive stimuli, and that both activities are positively correlated. Altogether, we identified a common neurobiological substrate linking negative valence with anxiety-related information and behaviors, which provides a starting point to understand how alterations of these neural populations contribute to psychiatric disorders.
Environmental and genetic predictors of human cardiovascular ageing
Authors: Shah Mit , de A. Inácio Marco H. , Lu Chang , Schiratti Pierre-Raphaël , Zheng Sean L. , Clement Adam , de Marvao Antonio , Bai Wenjia , King Andrew P. , Ware James S. , Wilkins Martin R. , Mielke Johanna , Elci Eren , Kryukov Ivan , McGurk Kathryn A. , Bender Christian , Freitag Daniel F. , O’Regan Declan P.
Published: August 2023

Cardiovascular ageing is a process that begins early in life and leads to a progressive change in structure and decline in function due to accumulated damage across diverse cell types, tissues and organs contributing to multi-morbidity. Damaging biophysical, metabolic and immunological factors exceed endogenous repair mechanisms resulting in a pro-fibrotic state, cellular senescence and end-organ damage, however the genetic architecture of cardiovascular ageing is not known. Here we use machine learning approaches to quantify cardiovascular age from image-derived traits of vascular function, cardiac motion and myocardial fibrosis, as well as conduction traits from electrocardiograms, in 39,559 participants of UK Biobank. Cardiovascular ageing is found to be significantly associated with common or rare variants in genes regulating sarcomere homeostasis, myocardial immunomodulation, and tissue responses to biophysical stress. Ageing is accelerated by cardiometabolic risk factors and we also identify prescribed medications that are potential modifiers of ageing. Through large-scale modelling of ageing across multiple traits our results reveal insights into the mechanisms driving premature cardiovascular ageing and reveal potential molecular targets to attenuate age-related processes.
Contribution of boundary non-stoichiometry to the lower-temperature plasticity in high-pressure sintered boron carbide
Authors: Xu Haiyue , Ji Wei , Jiang Jiawei , Liu Junliang , Wang Hao , Zhang Fan , Yu Ruohan , Tu Bingtian , Zhang Jinyong , Zou Ji , Wang Weimin , Wu Jinsong , Fu Zhengyi
Published: August 2023

The improvement of non-oxide ceramic plasticity while maintaining the high-temperature strength is a great challenge through the classical strategy, which generally includes decreasing grain size to several nanometers or adding ductile binder phase. Here, we report that the plasticity of fully dense boron carbide (B4C) is greatly enhanced due to the boundary non-stoichiometry induced by high-pressure sintering technology. The effect decreases the plastic deformation temperature of B4C by 200 °C compared to that of conventionally-sintered specimens. Promoted grain boundary diffusion is found to enhance grain boundary sliding, which dominate the lower-temperature plasticity. In addition, the as-produced specimen maintains extraordinary strength before the occurrence of plasticity. The study provides an efficient strategy by boundary chemical change to facilitate the plasticity of ceramic materials.
Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history
Authors: Hornsby Hailey , Nicols Alexander R. , Longet Stephanie , Liu Chang , Tomic Adriana , Angyal Adrienn , Kronsteiner Barbara , Tyerman Jessica K. , Tipton Tom , Zhang Peijun , Gallis Marta , Supasa Piyada , Selvaraj Muneeswaran , Abraham Priyanka , Neale Isabel , Ali Mohammad , Barratt Natalie A. , Nell Jeremy M. , Gustafsson Lotta , Strickland Scarlett , Grouneva Irina , Rostron Timothy , Moore Shona C. , Hering Luisa M. , Dobson Susan L. , Bibi Sagida , Mongkolsapaya Juthathip , Lambe Teresa , Wootton Dan , Hall Victoria , Hopkins Susan , Dong Tao , Barnes Eleanor , Screaton Gavin ,   The PITCH Consortium, Richter Alex , Turtle Lance , Rowland-Jones Sarah L. , Carroll Miles , Duncan Christopher J. A. , Klenerman Paul , Dunachie Susanna J. , Payne Rebecca P. , de Silva Thushan I.
Published: August 2023

Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.
TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
Authors: Scaramuzza Shaun , Jones Rebecca M. , Sadurni Martina Muste , Reynolds-Winczura Alicja , Poovathumkadavil Divyasree , Farrell Abigail , Natsume Toyoaki , Rojas Patricia , Cuesta Cyntia Fernandez , Kanemaki Masato T. , Saponaro Marco , Gambus Agnieszka
Published: August 2023

Cell division is the basis for the propagation of life and requires accurate duplication of all genetic information. DNA damage created during replication (replication stress) is a major cause of cancer, premature aging and a spectrum of other human disorders. Over the years, TRAIP E3 ubiquitin ligase has been shown to play a role in various cellular processes that govern genome integrity and faultless segregation. TRAIP is essential for cell viability, and mutations in TRAIP ubiquitin ligase activity lead to primordial dwarfism in patients. Here, we have determined the mechanism of inhibition of cell proliferation in TRAIP-depleted cells. We have taken advantage of the auxin induced degron system to rapidly degrade TRAIP within cells and to dissect the importance of various functions of TRAIP in different stages of the cell cycle. We conclude that upon rapid TRAIP degradation, specifically in S-phase, cells cease to proliferate, arrest in G2 stage of the cell cycle and undergo senescence. Our findings reveal that TRAIP works in S-phase to prevent DNA damage at transcription start sites, caused by replication-transcription conflicts.
Crystal structure and functional implications of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases
Authors: Yang Chia-Shin , Ko Tzu-Ping , Chen Chao-Jung , Hou Mei-Hui , Wang Yu-Chuan , Chen Yeh
Published: August 2023

Purine-containing nucleotide second messengers regulate diverse cellular activities. Cyclic di-pyrimidines mediate anti-phage functions in bacteria; however, the synthesis mechanism remains elusive. Here, we determine the high-resolution structures of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases (CD-NTases) in clade E (CdnE) in its apo, substrate-, and intermediate-bound states. A conserved (R/Q)xW motif controlling the pyrimidine specificity of donor nucleotide is identified. Mutation of Trp or Arg from the (R/Q)xW motif to Ala rewires its specificity to purine nucleotides, producing mixed purine-pyrimidine cyclic dinucleotides (CDNs). Preferential binding of uracil over cytosine bases explains the product specificity of cyclic di-pyrimidine-synthesizing CdnE to cyclic di-UMP (cUU). Based on the intermediate-bound structures, a synthetic pathway for cUU containing a unique 2’3’-phosphodiester linkage through intermediate pppU[3’−5’]pU is deduced. Our results provide a framework for pyrimidine selection and establish the importance of conserved residues at the C-terminal loop for the specificity determination of CD-NTases.
Redox driven B12-ligand switch drives CarH photoresponse
Authors: Poddar Harshwardhan , Rios-Santacruz Ronald , Heyes Derren J. , Shanmugam Muralidharan , Brookfield Adam , Johannissen Linus O. , Levy Colin W. , Jeffreys Laura N. , Zhang Shaowei , Sakuma Michiyo , Colletier Jacques-Philippe , Hay Sam , Schirò Giorgio , Weik Martin , Scrutton Nigel S. , Leys David
Published: August 2023

CarH is a coenzyme B12-dependent photoreceptor involved in regulating carotenoid biosynthesis. How light-triggered cleavage of the B12 Co-C bond culminates in CarH tetramer dissociation to initiate transcription remains unclear. Here, a series of crystal structures of the CarH B12-binding domain after illumination suggest formation of unforeseen intermediate states prior to tetramer dissociation. Unexpectedly, in the absence of oxygen, Co-C bond cleavage is followed by reorientation of the corrin ring and a switch from a lower to upper histidine-Co ligation, corresponding to a pentacoordinate state. Under aerobic conditions, rapid flash-cooling of crystals prior to deterioration upon illumination confirm a similar B12-ligand switch occurs. Removal of the upper His-ligating residue prevents monomer formation upon illumination. Combined with detailed solution spectroscopy and computational studies, these data demonstrate the CarH photoresponse integrates B12 photo- and redox-chemistry to drive large-scale conformational changes through stepwise Co-ligation changes.
CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis
Authors: Tang Zihan , Xu Yanyan , Tan Yun , Shi Hui , Jin Peipei , Li Yunqi , Teng Jialin , Liu Honglei , Pan Haoyu , Hu Qiongyi , Cheng Xiaobing , Ye Junna , Su Yutong , Sun Yue , Meng Jianfen , Zhou Zhuochao , Chi Huihui , Wang Xuefeng , Liu Junling , Lu Yong , Liu Feng , Dai Jing , Yang Chengde , Chen Saijuan , Liu Tingting
Published: August 2023

Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.
NFIB facilitates replication licensing by acting as a genome organizer
Authors: Zhang Wenting , Wang Yue , Liu Yongjie , Liu Cuifang , Wang Yizhou , He Lin , Cheng Xiao , Peng Yani , Xia Lu , Wu Xiaodi , Wu Jiajing , Zhang Yu , Sun Luyang , Chen Ping , Li Guohong , Tu Qiang , Liang Jing , Shang Yongfeng
Published: August 2023

The chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes.
At-home wearables and machine learning sensitively capture disease progression in amyotrophic lateral sclerosis
Authors: Gupta Anoopum S. , Patel Siddharth , Premasiri Alan , Vieira Fernando
Published: August 2023

Amyotrophic lateral sclerosis causes degeneration of motor neurons, resulting in progressive muscle weakness and impairment in motor function. Promising drug development efforts have accelerated in amyotrophic lateral sclerosis, but are constrained by a lack of objective, sensitive, and accessible outcome measures. Here we investigate the use of wearable sensors, worn on four limbs at home during natural behavior, to quantify motor function and disease progression in 376 individuals with amyotrophic lateral sclerosis. We use an analysis approach that automatically detects and characterizes submovements from passively collected accelerometer data and produces a machine-learned severity score for each limb that is independent of clinical ratings. We show that this approach produces scores that progress faster than the gold standard Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (−0.86 ± 0.70 SD/year versus −0.73 ± 0.74 SD/year), resulting in smaller clinical trial sample size estimates (N = 76 versusN = 121). This method offers an ecologically valid and scalable measure for potential use in amyotrophic lateral sclerosis trials and clinical care.
Heat is associated with short-term increases in household food insecurity in 150 countries and this is mediated by income
Authors: Kroeger Carolin
Published: August 2023

Rising temperatures are expected to stall progress on food insecurity by reducing agricultural yields in the coming decades. But hot periods may also increase food insecurity within days when it gets too hot to work and earn an income, thus limiting households’ capability to purchase food. Here I exploit variations in heat levels during a household survey spanning 150 countries in a quasi-natural experiment to show that particularly hot weeks are associated with higher chances of food insecurity among households (0.5767, 95% confidence interval 0.2958–0.8576, t = 4.024, d.f. = 427,816, P < 0.001). This association is mediated by reductions in income and health for households and the effects are stronger in countries with lower incomes and more agricultural or precarious forms of employment. The results highlight the importance of labour market disruptions for food insecurity and suggest integration of these concerns into heat action plans and food programmes.
Postacute sequelae of COVID-19 at 2 years
Authors: Bowe Benjamin , Xie Yan , Al-Aly Ziyad
Published: August 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection. The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals. Within the 80 prespecified sequelae, 69% and 35% of them became not significant at 2 years after infection among nonhospitalized and hospitalized individuals, respectively. Cumulatively at 2 years, PASC contributed 80.4 (95% confidence interval (CI): 71.6–89.6) and 642.8 (95% CI: 596.9–689.3) disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% (18.9–31.0%) and 21.3% (18.2–24.5%) of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year. In sum, while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection.
DUO-GAIT: A gait dataset for walking under dual-task and fatigue conditions with inertial measurement units
Authors: Zhou Lin , Fischer Eric , Brahms Clemens Markus , Granacher Urs , Arnrich Bert
Published: August 2023

In recent years, there has been a growing interest in developing and evaluating gait analysis algorithms based on inertial measurement unit (IMU) data, which has important implications, including sports, assessment of diseases, and rehabilitation. Multi-tasking and physical fatigue are two relevant aspects of daily life gait monitoring, but there is a lack of publicly available datasets to support the development and testing of methods using a mobile IMU setup. We present a dataset consisting of 6-minute walks under single- (only walking) and dual-task (walking while performing a cognitive task) conditions in unfatigued and fatigued states from sixteen healthy adults. Especially, nine IMUs were placed on the head, chest, lower back, wrists, legs, and feet to record under each of the above-mentioned conditions. The dataset also includes a rich set of spatio-temporal gait parameters that capture the aspects of pace, symmetry, and variability, as well as additional study-related information to support further analysis. This dataset can serve as a foundation for future research on gait monitoring in free-living environments.
Body mass trajectory from diagnosis to the end of treatment in a pediatric acute lymphoblastic leukemia cohort
Authors: Galati Paula Cristina , Rocha Priscilla Roberta Silva , Gruezo Nádia Dias , Amato Angélica Amorim
Published: August 2023

The advances in pediatric acute lymphoblastic leukemia (ALL) care have substantially increased survival, and the late effects of treatment are a growing concern. Obesity development is frequent following ALL therapy and may significantly contribute to long-term morbidity and mortality. We examined the body mass trajectory of 208 children with ALL, from the diagnosis to the completion of therapy. We found that 7.2% of children were overweight or obese at diagnosis, which increased to 19.7% at the end of induction therapy and 20.8% after completion of treatment. In a multivariable linear regression model, age at ALL diagnosis, the type of chemotherapy regimen, and body mass index (BMI) z-score at diagnosis were significant predictors of BMI z-score after induction therapy, whereas BMI z-score at diagnosis was the only significant predictor of BMI z-score at the completion of treatment. In a subgroup of 120 children, we found no association between nutrition status at diagnosis and the risk of ALL relapse or poorer overall survival. Our findings indicate that weight gain occurs early during ALL therapy and is predicted by weight status at diagnosis. Therefore, nutritional status should be assessed throughout treatment, and weight management interventions should be considered early, particularly for patients with higher weight at diagnosis.
Modeling abundance and risk impact of Vespa velutina nigrithorax (Hymenoptera: Vespidae) in Korea: application of a species abundance model
Authors: Kim Min-Jung , Bak Seongbin , Jung Chuleui
Published: August 2023

The Asian yellow-legged hornet, Vespa velutina nigrithorax, is native to Southeast Asia. However, it has invaded many countries in temperate regions, causing serious threats to honeybees and human health. With a growing demand for estimating the potential distribution of this species, multiple studies have resorted to occurrence-based models. However, they are less informative for predicting local abundance patterns associated with the species’ impact. Thus, we aimed to develop an abundance-based distribution model for V. v. nigrithorax in Korea to support the forecast of its impact and associated management strategies. The abundance data of V. v. nigrithorax were collected from 254 sites for 4 years covering the country and used to develop a model with bioclimatic and land composition variables. Along with the abundance model, the classical occurrence model was tested to determine whether it could provide a reasonable prediction on the estimation of local abundance. As a result, the abundance model provided higher discriminative power and accuracy than the occurrence model to evaluate the impacts caused by V. v. nigrithorax. On the other hand, the occurrence model was not able to discriminate abundance in the areas occupied by V. v. nigrithorax, indicating an unclear occurrence-abundance relationship or oversimplification of the estimated niche created by the occurrence model. Based on the final abundance model, risk indices for human health and honeybee losses were suggested. These results could help to provide support for risk management of V. v. nigrithorax in Korea and to give biological information to other countries where this species has already become established or which it is likely to invade in the near future.
Effect of the isotiazole adjuvants in combination with cisplatin in chemotherapy of neuroepithelial tumors: experimental results and modeling
Authors: Potkin Vladimir , Pushkarchuk Aliaxandr , Zamaro Alexandra , Zhou Hongwei , Kilin Sergey , Petkevich Sergey , Kolesnik Irina , Michels Dominik L. , Lyakhov Dmitry A. , Kulchitsky Vladimir A.
Published: August 2023

Chemotherapy is one of the main treatment options for cancer, but it is usually accompanied with negative side effects. The classical drugs combination with synergistic adjuvants can be the solution to this problem, allowing reducing therapeutic dose. Elucidating the mechanism of adjuvant action is of key importance for the selection of the optimal agent. Here we examine the system drug-adjuvant to explain the observed effect in practice. We used the first line drug cisplatin. Morpholinium and 4-methylpiperazinium 4,5-dichloro isothiazol-3-carboxylates were selected as adjuvants. The study of the cisplatin-adjuvant system was carried out by quantum chemical modeling using DFT. It turned out that adjuvants form conjugates with cisplatin that lead to the relocation of frontier molecular orbitals as well as increase of conjugate’s dipole moment. It resulted in change of the interaction character with DNA and increase of the bioactivity of the system. The data obtained are the basis for expanding the studies to include other drugs and adjuvants. Oncologists will have opportunity to use “classical” chemotherapy drugs in combination with synergists for those patients who have not been previously recommended to such a treatment because of pronounced toxic side effects.
Stabilization and racetrack application of asymmetric Néel skyrmions in hybrid nanostructures
Authors: Zelent Mateusz , Moalic Mathieu , Mruczkiewicz Michal , Li Xiaoguang , Zhou Yan , Krawczyk Maciej
Published: August 2023

Magnetic skyrmions, topological quasiparticles, are small stable magnetic textures that possess intriguing properties and potential for data storage applications. Hybrid nanostructures comprised of skyrmions and soft magnetic material can offer additional advantages for developing skyrmion-based spintronic and magnonic devices. We show that a Néel-type skyrmion confined within a nanodot placed on top of a ferromagnetic in-plane magnetized stripe produces a unique and compelling platform for exploring the mutual coupling between magnetization textures. The skyrmion induces an imprint upon the stripe, which, in turn, asymmetrically squeezes the skyrmion in the dot, increasing their size and the range of skyrmion stability at small values of Dzyaloshinskii–Moriya interaction, as well as introducing skyrmion bi-stability. Finally, by exploiting the properties of the skyrmion in a hybrid system, we demonstrate unlimited skyrmion transport along a racetrack, free of the skyrmion Hall effect.
Supply chain management with uncertainty in consumer perception of product greenness under an eco-label policy
Authors: Gao Jingzhe , Wei Haixiao
Published: August 2023

The urgency of environmental preservation necessitates green manufacturing and supply chain advancements. This research examines a green supply chain problem influenced by eco-label policies, focusing on two prevalent market eco-label types. One allows the manufacturer to determine product greenness, while the other requires compliance with standards set by a non-governmental organization (NGO). We also explore the variability in consumer comprehension of eco-label implications and purchasing behaviors with different eco-labeled products. Through consumer utility and manufacturer profit models, we discover that the manufacturer's production and pricing choices significantly impact consumer behavior. Increased investigation costs may enhance consumer utility through improved product greenness, potentially boosting manufacturer profit via price hikes. However, if investigation costs are minimal, the NGO-label may be rejected due to decreased utility and profit. These insights could help direct supply chains by providing a theoretical foundation for green production decisions and future eco-label policies, whether determined by an NGO or the manufacturer.
A content analysis of YouTube videos on tinnitus in South Korea
Authors: Seo Hee Won , Ha Jung Woo , Kwak Jin Hye , Kim Moo Keon , Byun Hayoung , Lee Seung Hwan , Chung Jae Ho
Published: August 2023

More people use the internet for medical information, especially YouTube. Nevertheless, no study has been conducted to analyze the quality of YouTube videos about tinnitus in Korea. This study aims to review the contents and quality of YouTube videos on tinnitus. The top 100 Korean YouTube videos on tinnitus were reviewed by a tinnitus expert. This study assessed video details: title, creator, length, and popularity indicators—subscribers, views, and likes. The contents of the video clips were analyzed to determine the relevance, understandability, actionability, and quality of information. Out of 100 tinnitus videos, 27 were created by otolaryngologists, 25 by traditional Korean medicine doctors, 25 by other medical professionals, and 3 by lay persons. Sensorineural tinnitus was frequently dealt, and hearing loss, stress, and noise were introduced as main causes of tinnitus. Otolaryngologists' videos covered verified treatments, but others suggested unproven therapies including herbal medicine or acupressure. Otolaryngologists' videos showed significantly higher understandability and quality of information compared to others (p < 0.001). This study found that tinnitus YouTube videos frequently present low-quality and incorrect material, which could have an adverse effect on patients. Results highlight the need for tinnitus specialists to provide accurate information.
Site-specific phosphorylations of the Arf activator GBF1 differentially regulate GBF1 function in Golgi homeostasis and secretion versus cytokinesis
Authors: Walton Kendall , Nawara Tomasz J. , Angermeier Allyson R. , Rosengrant Hadley , Lee Eunjoo , Wynn Bridge , Victorova Ekaterina , Belov George , Sztul Elizabeth
Published: August 2023

Diverse cellular processes, including membrane traffic, lipid homeostasis, cytokinesis, mitochondrial positioning, and cell motility are critically dependent on the Sec7 domain guanine nucleotide exchange factor GBF1. Yet, how the participation of GBF1 in a particular cellular function is regulated is unknown. Here, we show that the phosphorylation of specific highly conserved serine and tyrosine residues within the N-terminal domain of GBF1 differentially regulates its function in maintaining Golgi homeostasis and facilitating secretion versus its role in cytokinesis. Specifically, GBF1 mutants containing single amino acid substitutions that mimic a stably phosphorylated S233, S371, Y377, and Y515 or the S233A mutant that can’t be phosphorylated are fully able to maintain Golgi architecture and support cargo traffic through the secretory pathway when assessed in multiple functional assays. However, the same mutants cause multi-nucleation when expressed in cells, and appear to inhibit the progression through mitosis and the resolution of cytokinetic bridges. Thus, GBF1 participates in distinct interactive networks when mediating Golgi homeostasis and secretion versus facilitating cytokinesis, and GBF1 integration into such networks is differentially regulated by the phosphorylation of specific GBF1 residues.
An active learning machine technique based prediction of cardiovascular heart disease from UCI-repository database
Authors: Srinivasan Saravanan , Gunasekaran Subathra , Mathivanan Sandeep Kumar , M. B Benjula Anbu Malar , Jayagopal Prabhu , Dalu Gemmachis Teshite
Published: August 2023

Heart disease is a significant global cause of mortality, and predicting it through clinical data analysis poses challenges. Machine learning (ML) has emerged as a valuable tool for diagnosing and predicting heart disease by analyzing healthcare data. Previous studies have extensively employed ML techniques in medical research for heart disease prediction. In this study, eight ML classifiers were utilized to identify crucial features that enhance the accuracy of heart disease prediction. Various combinations of features and well-known classification algorithms were employed to develop the prediction model. Neural network models, such as Naïve Bayes and Radial Basis Functions, were implemented, achieving accuracies of 94.78% and 90.78% respectively in heart disease prediction. Among the state-of-the-art methods for cardiovascular problem prediction, Learning Vector Quantization exhibited the highest accuracy rate of 98.7%. The motivation behind predicting Cardiovascular Heart Disease lies in its potential to save lives, improves health outcomes, and allocates healthcare resources efficiently. The key contributions encompass early intervention, personalized medicine, technological advancements, the impact on public health, and ongoing research, all of which collectively work toward reducing the burden of CHD on both individual patients and society as a whole.
Development of a thoron calibration chamber based on computational fluid dynamics simulation and validation with measurements
Authors: Adelikhah Mohammademad , Imani Morteza , Kovács Tibor
Published: August 2023

Recently, interest in measuring the concentration of 220Rn in air has increased greatly following the development of standards and the calibration of monitoring instruments. In this study, a 220Rn calibration chamber was designed and developed at the Institute of Radiochemistry and Radioecology (RRI) based on the computational fluid dynamics (CFD) method implemented in ANSYS Fluent 2020 R1 code at the University of Pannonia in Hungary. The behavior of 220Rn and its spatial distribution inside the 220Rn calibration chamber at RRI were investigated at different flow rates. The 220Rn concentration was close to homogeneous under higher flow regimes due to thorough mixing of the gas inside the chamber. Predictions based on CFD simulations were compared with experimentally measured transmission factors (Cout/Cin). The spatial distribution of 220Rn was dependent on the flow rate and the positions of the inlet and outlet. Our results clearly demonstrate the suitability of the 220Rn calibration chamber at RRI for calibrating monitoring instruments. Furthermore, the CFD-based predictions were in good agreement with the results obtained at higher flow rates using experimental and analytical models according to the relative deviation, with a maximum of approximately 9%.