bluuebunny/crossref_metadata_2025 huggingface dataset:
What dictates soft clay-like lithium superionic conductor formation from rigid salts mixture
Authors: Gupta Sunny , Yang Xiaochen , Ceder Gerbrand
Published: October 2023

Soft clay-like Li-superionic conductors, integral to realizing all-solid-state batteries, have been recently synthesized by mixing rigid-salts. Here, through computational and experimental analysis, we clarify how a soft clay-like material can be created from a mixture of rigid-salts. Using molecular dynamics simulations with a deep learning-based interatomic potential energy model, we uncover the microscopic features responsible for soft clay-formation from ionic solid mixtures. We find that salt mixtures capable of forming molecular solid units on anion exchange, along with the slow kinetics of such reactions, are key to soft-clay formation. Molecular solid units serve as sites for shear transformation zones, and their inherent softness enables plasticity at low stress. Extended X-ray absorption fine structure spectroscopy confirms the formation of molecular solid units. A general strategy for creating soft clay-like materials from ionic solid mixtures is formulated.
Hierarchical AI enables global interpretation of culture plates in the era of digital microbiology
Authors: Signoroni Alberto , Ferrari Alessandro , Lombardi Stefano , Savardi Mattia , Fontana Stefania , Culbreath Karissa
Published: October 2023

Full Laboratory Automation is revolutionizing work habits in an increasing number of clinical microbiology facilities worldwide, generating huge streams of digital images for interpretation. Contextually, deep learning architectures are leading to paradigm shifts in the way computers can assist with difficult visual interpretation tasks in several domains. At the crossroads of these epochal trends, we present a system able to tackle a core task in clinical microbiology, namely the global interpretation of diagnostic bacterial culture plates, including presumptive pathogen identification. This is achieved by decomposing the problem into a hierarchy of complex subtasks and addressing them with a multi-network architecture we callDeepColony. Working on a large stream of clinical data and a complete set of 32 pathogens, the proposed system is capable of effectively assist plate interpretation with a surprising degree of accuracy in the widespread and demanding framework of Urinary Tract Infections. Moreover, thanks to the rich species-related generated information,DeepColonycan be used for developing trustworthy clinical decision support services in laboratory automation ecosystems from local to global scale.
A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability
Authors: Li Ke , Guo Jiawei , Ming Yue , Chen Shuang , Zhang Tingting , Ma Hulin , Fu Xin , Wang Jin , Liu Wenrong , Peng Yong
Published: October 2023

Metastasis is the leading cause of cancer-related death, where TGFβ-induced epithelial-mesenchymal transition (EMT) process confers on cancer cells increased metastatic potential. However, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA called circITGB6 as an indispensable factor during the TGFβ-mediated EMT process. circITGB6 is significantly upregulated in metastatic cancer samples and its higher abundance is closely correlated to worse prognosis of colorectal cancer (CRC) patients. Through gain- and loss-of-function assays, circITGB6 is found to potently promote EMT process and tumor metastasis in various models in vitro and in vivo. Mechanistically, circITGB6 enhances the mRNA stability of PDPN, an EMT-promoting gene, by directly interacting with IGF2BP3. Notably, interfering circITGB6 with PEI-coated specific siRNA effectively represses liver metastasis. Therefore, our study reveals the function of a TGFβ-regulated circRNA in tumor metastasis and suggests that targeting circITGB6 is a promising strategy for cancer therapy.
Enhanced clinical assessment of hematologic malignancies through routine paired tumor and normal sequencing
Authors: Ptashkin Ryan N. , Ewalt Mark D. , Jayakumaran Gowtham , Kiecka Iwona , Bowman Anita S. , Yao JinJuan , Casanova Jacklyn , Lin Yun-Te David , Petrova-Drus Kseniya , Mohanty Abhinita S. , Bacares Ruben , Benhamida Jamal , Rana Satshil , Razumova Anna , Vanderbilt Chad , Balakrishnan Rema Anoop , Rijo Ivelise , Son-Garcia Julie , de Bruijn Ino , Zhu Menglei , Lachhander Sean , Wang Wei , Haque Mohammad S. , Seshan Venkatraman E. , Wang Jiajing , Liu Ying , Nafa Khedoudja , Borsu Laetitia , Zhang Yanming , Aypar Umut , Suehnholz Sarah P. , Chakravarty Debyani , Park Jae H. , Abdel-Wahab Omar , Mato Anthony R. , Xiao Wenbin , Roshal Mikhail , Yabe Mariko , Batlevi Connie Lee , Giralt Sergio , Salles Gilles , Rampal Raajit , Tallman Martin , Stein Eytan M. , Younes Anas , Levine Ross L. , Perales Miguel-Angel , van den Brink Marcel R. M. , Dogan Ahmet , Ladanyi Marc , Berger Michael F. , Brannon A. Rose , Benayed Ryma , Zehir Ahmet , Arcila Maria E.
Published: October 2023

Genomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.
XMAP: Cross-population fine-mapping by leveraging genetic diversity and accounting for confounding bias
Authors: Cai Mingxuan , Wang Zhiwei , Xiao Jiashun , Hu Xianghong , Chen Gang , Yang Can
Published: October 2023

Fine-mapping prioritizes risk variants identified by genome-wide association studies (GWASs), serving as a critical step to uncover biological mechanisms underlying complex traits. However, several major challenges still remain for existing fine-mapping methods. First, the strong linkage disequilibrium among variants can limit the statistical power and resolution of fine-mapping. Second, it is computationally expensive to simultaneously search for multiple causal variants. Third, the confounding bias hidden in GWAS summary statistics can produce spurious signals. To address these challenges, we develop a statistical method for cross-population fine-mapping (XMAP) by leveraging genetic diversity and accounting for confounding bias. By using cross-population GWAS summary statistics from global biobanks and genomic consortia, we show that XMAP can achieve greater statistical power, better control of false positive rate, and substantially higher computational efficiency for identifying multiple causal signals, compared to existing methods. Importantly, we show that the output of XMAP can be integrated with single-cell datasets, which greatly improves the interpretation of putative causal variants in their cellular context at single-cell resolution.
Impact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study
Authors: Otiende M. , Nyaguara A. , Bottomley C. , Walumbe D. , Mochamah G. , Amadi D. , Nyundo C. , Kagucia E. W. , Etyang A. O. , Adetifa I. M. O. , Brand S. P. C. , Maitha E. , Chondo E. , Nzomo E. , Aman R. , Mwangangi M. , Amoth P. , Kasera K. , Ng’ang’a W. , Barasa E. , Tsofa B. , Mwangangi J. , Bejon P. , Agweyu A. , Williams T. N. , Scott J. A. G.
Published: October 2023

The mortality impact of COVID-19 in Africa remains controversial because most countries lack vital registration. We analysed excess mortality in Kilifi Health and Demographic Surveillance System, Kenya, using 9 years of baseline data. SARS-CoV-2 seroprevalence studies suggest most adults here were infected before May 2022. During 5 waves of COVID-19 (April 2020-May 2022) an overall excess mortality of 4.8% (95% PI 1.2%, 9.4%) concealed a significant excess (11.6%, 95% PI 5.9%, 18.9%) among older adults ( ≥ 65 years) and a deficit among children aged 1–14 years (−7.7%, 95% PI −20.9%, 6.9%). The excess mortality rate for January 2020-December 2021, age-standardised to the Kenyan population, was 27.4/100,000 person-years (95% CI 23.2-31.6). In Coastal Kenya, excess mortality during the pandemic was substantially lower than in most high-income countries but the significant excess mortality in older adults emphasizes the value of achieving high vaccine coverage in this risk group.
Shade-induced RTFL/DVL peptides negatively regulate the shade response by directly interacting with BSKs in Arabidopsis
Authors: Huang Sha , Ma Yu , Xu Yitian , Lu Pengfei , Yang Jie , Xie Yu , Gan Jianhua , Li Lin
Published: October 2023

For shade-intolerant species, shade light indicates the close proximity of neighboring plants and triggers the shade avoidance syndrome (SAS), which causes exaggerated growth and reduced crop yield. Here, we report that non-secreted ROT FOUR LIKE (RTFL)/DEVIL (DVL) peptides negatively regulate SAS by interacting with BRASSINOSTEROID SIGNALING KINASEs (BSKs) and reducing the protein level of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) in Arabidopsis. The transcription of at least five RTFLs (RTFL13/16/17/18/21) is induced by low R:FR light. The RTFL18 (DVL1) protein is stabilized under low R:FR conditions and localized to the plasma membrane. A phenotype analysis reveals that RTFL18 negatively regulates low R:FR-promoted petiole elongation. BSK3 and BSK6 are identified as partners of RTFL18 through binding assays and structural modeling. The overexpression of RTFL18 or knockdown of BSK3/6 reduces BRASSINOSTEROID signaling and reduces low R:FR-stabilized PIF4 levels. Genetically, the overexpression of BSK3/6 and PIF4 restores the petiole phenotype acquired by RTFL18-overexpressing lines. Collectively, our work characterizes a signaling cascade (the RTFLs-BSK3/6-PIF4 pathway) that prevents the excessive activation of the shade avoidance response in Arabidopsis.
Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state
Authors: You In-Jee , Bae Yeeun , Beck Alec R. , Shin Sora
Published: October 2023

Psychological stressors, like the nearby presence of a predator, can be strong enough to induce physiological/hormonal alterations, leading to appetite changes. However, little is known about how threats can alter feeding-related hypothalamic circuit functions. Here, we found that proenkephalin (Penk)-expressing lateral hypothalamic (LHPenk) neurons of mice exposed to predator scent stimulus (PSS) show sensitized responses to high-fat diet (HFD) eating, whereas silencing of the same neurons normalizes PSS-induced HFD overconsumption associated with a negative emotional state. Downregulation of endogenous enkephalin peptides in the LH is crucial for inhibiting the neuronal and behavioral changes developed after PSS exposure. Furthermore, elevated corticosterone after PSS contributes to enhance the reactivity of glucocorticoid receptor (GR)-containing LHPenk neurons to HFD, whereas pharmacological inhibition of GR in the LH suppresses PSS-induced maladaptive behavioral responses. We have thus identified the LHPenk neurons as a critical component in the threat-induced neuronal adaptation that leads to emotional overconsumption.
A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
Authors: Liu Di-Ao , Tao Kai , Wu Bin , Yu Ziyan , Szczepaniak Malwina , Rames Matthew , Yang Changsong , Svitkina Tatyana , Zhu Yueyao , Xu Fengyuan , Nan Xiaolin , Guo Wei
Published: October 2023

Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion.
α-Synuclein aggregates amplified from patient-derived Lewy bodies recapitulate Lewy body diseases in mice
Authors: Uemura Norihito , Marotta Nicholas P. , Ara Jahan , Meymand Emily S. , Zhang Bin , Kameda Hiroshi , Koike Masato , Luk Kelvin C. , Trojanowski John Q. , Lee Virginia M.-Y.
Published: October 2023

Extraction of α-Synuclein (αSyn) aggregates from Lewy body disease (LBD) brains has been widely described yet templated fibrillization of LB-αSyn often fails to propagate its structural and functional properties. We recently demonstrated that aggregates amplified from LB-αSyn (ampLB) show distinct biological activities in vitro compared to human αSyn preformed fibrils (hPFF) formed de novo. Here we compare the in vivo biological activities of hPFF and ampLB regarding seeding activity, latency in inducing pathology, distribution of pathology, inclusion morphology, and cell-type preference. Injection of ampLB into mice expressing only human αSyn (male Thy1:SNCA/Snca–/– mice) induced pathologies similar to those of LBD subjects that were distinct from those induced by hPFF-injection or developing spontaneously with aging. Importantly, αSyn aggregates in ampLB-injected Thy1:SNCA/Snca–/– mice maintained the unique biological and conformational features of original LB-αSyn. These results indicate that ampLB-injection, rather than conventional PFF-injection or αSyn overexpression, faithfully models key aspects of LBD.
Structural titration reveals Ca2+-dependent conformational landscape of the IP3 receptor
Authors: Paknejad Navid , Sapuru Vinay , Hite Richard K.
Published: October 2023

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are endoplasmic reticulum Ca2+ channels whose biphasic dependence on cytosolic Ca2+ gives rise to Ca2+ oscillations that regulate fertilization, cell division and cell death. Despite the critical roles of IP3R-mediated Ca2+ responses, the structural underpinnings of the biphasic Ca2+ dependence that underlies Ca2+ oscillations are incompletely understood. Here, we collect cryo-EM images of an IP3R with Ca2+ concentrations spanning five orders of magnitude. Unbiased image analysis reveals that Ca2+ binding does not explicitly induce conformational changes but rather biases a complex conformational landscape consisting of resting, preactivated, activated, and inhibited states. Using particle counts as a proxy for relative conformational free energy, we demonstrate that Ca2+ binding at a high-affinity site allows IP3Rs to activate by escaping a low-energy resting state through an ensemble of preactivated states. At high Ca2+ concentrations, IP3Rs preferentially enter an inhibited state stabilized by a second, low-affinity Ca2+ binding site. Together, these studies provide a mechanistic basis for the biphasic Ca2+-dependence of IP3R channel activity.
Efficient photocatalytic production of hydrogen peroxide using dispersible and photoactive porous polymers
Authors: Wang Shengdong , Xie Zhipeng , Zhu Da , Fu Shuai , Wu Yishi , Yu Hongling , Lu Chuangye , Zhou Panke , Bonn Mischa , Wang Hai I. , Liao Qing , Xu Hong , Chen Xiong , Gu Cheng
Published: October 2023

Developing efficient artificial photocatalysts for the biomimetic photocatalytic production of molecular materials, including medicines and clean energy carriers, remains a fundamentally and technologically essential challenge. Hydrogen peroxide is widely used in chemical synthesis, medical disinfection, and clean energy. However, the current industrial production, predominantly by anthraquinone oxidation, suffers from hefty energy penalties and toxic byproducts. Herein, we report the efficient photocatalytic production of hydrogen peroxide by protonation-induced dispersible porous polymers with good charge-carrier transport properties. Significant photocatalytic hydrogen peroxide generation occurs under ambient conditions at an unprecedented rate of 23.7 mmol g–1 h–1 and an apparent quantum efficiency of 11.3% at 450 nm. Combined simulations and spectroscopies indicate that sub-picosecond ultrafast electron “localization” from both free carriers and exciton states at the catalytic reaction centers underlie the remarkable photocatalytic performance of the dispersible porous polymers.
Mapping the spatial heterogeneity of global land use and land cover from 2020 to 2100 at a 1 km resolution
Authors: Zhang Tianyuan , Cheng Changxiu , Wu Xudong
Published: October 2023

A fine global future land use/land cover (LULC) is critical for demonstrating the geographic heterogeneity of earth system dynamics and human-earth interaction. In this study, we produced a 1 km global future LULC dataset that takes into account future climate and socio-economic changes as well as the impact of simulated results of the former year on temporally adjacent periods. By incorporating the variations in climatic and socio-economic factors, we differentiated LULC suitability probabilities for historical and future periods across representative SSP-RCP scenarios. Then, by using an improved cellular automata model-PLUS to simulate the patch-level changes of various land classes, we iteratively downscaled water-basin-level LULC demands in various future scenarios to a spatial resolution of 1 km. Our dataset achieves a high degree of simulation accuracy (Kappa = 0.94, OA = 0.97, FoM = 0.10) and precisely captures the spatial-temporal heterogeneity of global LULC changes under the combined effects of climate change and socio-economic development. This robust and fine-scale LULC dataset provides valuable spatially-explicit information essential for earth system modeling and intricate dynamics between anthropogenic activities and the environment.
Shared biomarkers and immune cell infiltration signatures in ulcerative colitis and nonalcoholic steatohepatitis
Authors: Wang Wenxin , Gao Xin , Kang Ning , Wang Chen , Li Chenyang , Yu Huan , Zhang Xiaolan
Published: October 2023

The coexistence of ulcerative colitis (UC) and nonalcoholic steatohepatitis (NASH) involves a intricate interplay, though the precise pathophysiological mechanisms remain elusive. To shed light on this, our study endeavors to unravel the shared gene signatures and molecular mechanisms by employing quantitative bioinformatics analysis on a publicly available RNA-sequencing database. Gene expression profiles of UC (GSE87466) and NASH (GSE89632) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using R software. After identifying common DEGs, functional enrichment analysis, protein–protein interaction (PPI) network analysis and module construction were performed to obtain candidate hub genes. GSE47908 for UC and GSE159676 for NASH were selected to validate the obtained candidate genes. A total of 119 common DEGs were found in NASH and UC patients. Functional and pathway analyses emphasized that viral infection, inflammation and immune response were enriched in these two diseases. After module construction and validation, CD2, CD8A, GNLY, IFI44, NKG7 and OAS2 were identified as hub genes. 6 hub genes and their combined prediction scores were found with an impressive accuracy and sensitivity. Functional estimation, gene set enrichment analysis and immune infiltration signature identification showed notable associations of the six hub genes with T cells, natural killer cells and type I interferon levels. In addition, we constructed UC combined with NASH mice model successfully with significantly higher expression of hub genes in both liver and colonic tissues than those in control group. Our study elucidates 6 hub genes of UC and NASH, which may participate in immune, inflammatory and antiviral effects. These findings provide some potential biochemical markers for further exploration of UC coexistence with NASH.
The impact of over-distraction on adjacent segment pathology and cage subsidence in anterior cervical discectomy and fusion
Authors: Hsueh Lan-Li , Yeh Yu-Cheng , Lu Meng-Ling , Luo Chi-An , Chiu Ping-Yeh , Lai Po-Liang , Niu Chi-Chien
Published: October 2023

Over-distraction has been shown to be a risk factor for cage subsidence and postoperative neck pain after anterior cervical discectomy and fusion (ACDF). Biomechanical studies have demonstrated increased adjacent segment intradiscal pressure after ACDF. The purpose of this study is to determine if over-distraction of the index disc has an effect on adjacent segment pathology. A consecutive series of 145 patients who received primary ACDF for cervical degenerative pathologies from January 2010 to December 2017 were retrospectively reviewed. The patients were divided into: (1) Over-distraction group (postoperative–preoperative index disc height ≥ 2 mm), and (2) No-distraction group (postoperative–preoperative index disc height < 2 mm). Outcome measures included radiographic parameters, Japanese Orthopaedic Association (JOA) score, and incidences of cage subsidence, radiological and clinical adjacent segment pathologies (RASP and CASP) were compared between the two groups preoperatively, postoperatively, and at the final follow-up. The two groups were comparable with respect to age, follow-up length, JOA score, incidence of CASP, and radiographic parameters. The Over-distraction group (83 patients; 115 levels) had smaller preoperative index disc height (4.5 vs. 5.2 mm, p < 0.001), but taller postoperative index disc height (7.7 vs. 6.6 mm, p < 0.001) than No-distraction group (62 patients; 90 levels) Furthermore, significantly higher incidences of cage subsidence (47% vs. 31%, p = 0.04) and RASP (any progression: 48% vs. 15%, p < 0.001; progress ≥ 2 grades: 25% vs. 7%, p = 0.001) were observed in the Over-distraction group. The multivariate analysis indicated that over-distraction and multilevel fusion were independent risk factors for RASP. There were no clinical outcome differences between the Over-distraction group and the No-distraction group in ACDF. Over-distraction of the index level of ≥ 2 mm should be avoided because it significantly increases the incidences of RASP and cage subsidence.
Fuzzy logic control for watering system
Authors: Neugebauer Maciej , Akdeniz Cengiz , Demir Vedat , Yurdem Hüseyin
Published: October 2023

A two-dimensional finite element (FEM) model was developed to simulate water propagation in soil during irrigation. The first dimension was water distribution depth in soil, and the second dimension was time. The developed model was tested by analyzing water distribution in a conventional (clock-controlled) irrigation model. The values in the conventional model were calculated based on the literature. The results were consistent with the results obtained from the model. In the next step, a fuzzy logic model for irrigation control was developed. The input variables were ambient temperature, soil moisture content and time of day (which is related to solar radiation and evapotranspiration), and the output variable was irrigation intensity. The fuzzy logic control (FLC) model was tested by simulating water distribution in soil and comparing water consumption in both models. The study demonstrated that the depth of the soil moisture sensor affected water use in the fuzzy logic-controlled irrigation system relative to the conventional model. Water consumption was reduced by around 12% when the soil moisture sensor was positioned at an optimal depth, but it increased by around 20% when sensor depth was not optimal. The extent to which the distribution of fuzzy variables affects irrigation performance was examined, and the analysis revealed that inadequate distribution of fuzzy variables in the irrigation control system can increase total water consumption by up to 38% relative to the conventional model. It can be concluded that a fuzzy logic-controlled irrigation system can reduce water consumption, but the system’s operating parameters should be always selected based on an analysis of local conditions to avoid an unintended increase in water use. A well-designed FLC can decrease water use in agriculture (thus contributing to rational management of scarce water resources), decrease energy consumption, and reduce the risk of crop pollution with contaminated groundwater.
Early to sustained impacts of lethal radiation on circulating miRNAs in a minipig model
Authors: Chakraborty Nabarun , Holmes-Hampton Gregory P. , Gautam Aarti , Kumar Raina , Hritzo Bernadette , Legesse Betre , Dimitrov George , Ghosh Sanchita P. , Hammamieh Rasha
Published: October 2023

Early diagnosis of lethal radiation is imperative since its intervention time windows are considerably short. Hence, ideal diagnostic candidates of radiation should be easily accessible, enable to inform about the stress history and objectively triage subjects in a time-efficient manner. Therefore, the small molecules such as metabolites and microRNAs (miRNAs) from plasma are legitimate biomarker candidate for lethal radiation. Our objectives were to comprehend the radiation-driven molecular pathogenesis and thereby determine biomarkers of translational potential. We investigated an established minipig model of LD70/45 total body irradiation (TBI). In this pilot study, plasma was collected pre-TBI and at multiple time points post-TBI. The majority of differentially expressed miRNAs and metabolites were perturbed immediately after TBI that potentially underlined the severity of its acute impact. The integrative network analysis of miRNA and metabolites showed a cohesive response; the early and consistent perturbations of networks were linked to cancer and the shift in musculoskeletal atrophy synchronized with the comorbidity-networks associated with inflammation and bioenergy synthesis. Subsequent comparative pipeline delivered 92 miRNAs, which demonstrated sequential homology between human and minipig, and potentially similar responses to lethal radiation across these two species. This panel promised to retrospectively inform the time since the radiation occurred; thereby could facilitate knowledge-driven interventions.
Effect of restrictive cumulative fluid balance on 28-day survival in invasively ventilated patients with moderate to severe ARDS due to COVID-19
Authors: Esper Treml Ricardo , Caldonazo Tulio , Filho Pedro Hilton A. , Mori Andréia L. , Carvalho André S. , Serrano Juliana S. F. , Dall-Aglio Pedro A. T. , Radermacher Peter , Manoel João Silva
Published: October 2023

This study aimed to evaluate the effect of two restrictive cumulative fluid balance (CFB) trends on survival and on major clinical outcomes in invasively ventilated patients with moderate to severe respiratory distress syndrome (ARDS) due to SARS-CoV-2. Prospective data collection was conducted on patients in the intensive care unit (ICU) originating from a tertiary university hospital. The primary outcomes were the risk association between the CFB trend during D0to D7and 28-day survival. The secondary outcomes were ICU mortality, in-hospital mortality, the need for invasive ventilation at D28, administration of vasoactive drugs at D7, time on invasive ventilation after D7, and length of ICU and hospital stay. 171 patients were enrolled in the study and divided according to their CFB trends during seven days of follow-up using model-based clustering [median CFB negative trend (n = 89) – 279 ml (− 664 to 203) and (n = 82) median CFB positive trend 1362 ml (619–2026)]. The group with CFB negative trend showed a higher chance of surviving 28-day in the ICU (HR: 0.62, 95% CI 0.41–0.94, p = 0.038). Moreover, this group had a reduced length of stay in the ICU, 11 (8–19) days versus 16.5 (9–29) daysp = 0.004 and presented lower rates (OR = 0.22; 95% CI 0.09–0.52) of invasive ventilation after 28-days in the ICU. In patients invasively ventilated with moderate to severe ARDS due to COVID-19, the collective who showed a negative trend in the CFB after seven days of invasive ventilation had a higher chance of surviving 28 days in the ICU and lower length of stay in the ICU.
Spatial correlation of 2D hard-tissue histology with 3D microCT scans through 3D printed phantoms
Authors: Nolte Philipp , Brettmacher Marcel , Gröger Chris Johann , Gellhaus Tim , Svetlove Angelika , Schilling Arndt F. , Alves Frauke , Rußmann Christoph , Dullin Christian
Published: October 2023

Hard-tissue histology—the analysis of thin two-dimensional (2D) sections—is hampered by the opaque nature of most biological specimens, especially bone. Therefore, the cutting process cannot be assigned to regions of interest. In addition, the applied cutting-grinding method is characterized by significant material loss. As a result, relevant structures might be missed or destroyed, and 3D features can hardly be evaluated. Here, we present a novel workflow, based on conventual microCT scans of the specimen prior to the cutting process, to be used for the analysis of 3D structural features and for directing the sectioning process to the regions of interest. 3D printed fiducial markers, embedded together with the specimen in resin, are utilized to retrospectively register the obtained 2D histological images into the 3D anatomical context. This not only allows to identify the cutting position, but also enables the co-registration of the cell and extracellular matrix morphological analysis to local 3D information obtained from the microCT data. We have successfully applied our new approach to assess hard-tissue specimens of different species. After matching the predicted microCT cut plane with the histology image, we validated a high accuracy of the registration process by computing quality measures namely Jaccard and Dice similarity coefficients achieving an average score of 0.90 ± 0.04 and 0.95 ± 0.02, respectively. Thus, we believe that the novel, easy to implement correlative imaging approach holds great potential for improving the reliability and diagnostic power of classical hard-tissue histology.
A solvent-free HPLC method for the simultaneous determination of Favipiravir and its hydrolytic degradation product
Authors: Sharaf Yasmine Ahmed , Abd El-Fattah Mai H. , El-Sayed Heba M. , Hassan Said A.
Published: October 2023

During COVID-19 pandemic, Favipiravir (FPV) showed a great efficacy against COVID-19 virus, it produced noticeable improvements in recovery of the patients. The aim of this study was to develop a new, green and simple method for the simultaneous determination of FPV and its acid-induced degradation product (ADP) in its pure and pharmaceutical dosage forms. This method will be key for the inevitable development of FPV solution and inhaler formulations. A green micellar RP-HPLC method was developed using an RP-VDSPHERE PUR 100 column (5 µm, 250 × 4.6 mm) and an isocratic mixed micellar mobile phase composed of 0.02 M Brij-35, 0.1 M SDS and 0.01 M potassium dihydrogen orthophosphate anhydrous and adjusted to pH 3.0 with 1.0 mL min−1flow rate. The detection was performed at 280 nm with a run time of less than six min. Under the optimized chromatographic conditions, linear relationship has been established between peak area and concentration of FPV and its ADP in the range of 5–100 and 10–100 µg mL−1with elution time of 3.8 and 5.7 min, respectively. The developed method was validated according to the ICH guidelines and applied successfully for determination of FPV in its pharmaceutical dosage form.
Genetic variation in the human leukocyte antigen region confers susceptibility to Clostridioides difficile infection
Authors: Ferar Kathleen , Hall Taryn O. , Crawford Dana C. , Rowley Robb , Satterfield Benjamin A. , Li Rongling , Gragert Loren , Karlson Elizabeth W. , de Andrade Mariza , Kullo Iftikhar J. , McCarty Catherine A. , Kho Abel , Hayes M. Geoffrey , Ritchie Marylyn D. , Crane Paul K. , Mirel Daniel B. , Carlson Christopher , Connolly John J. , Hakonarson Hakon , Crenshaw Andrew T. , Carrell David , Luo Yuan , Dikilitas Ozan , Denny Joshua C. , Jarvik Gail P. , Crosslin David R.
Published: October 2023

Clostridioides difficile (C. diff.) infection (CDI) is a leading cause of hospital acquired diarrhea in North America and Europe and a major cause of morbidity and mortality. Known risk factors do not fully explain CDI susceptibility, and genetic susceptibility is suggested by the fact that some patients with colons that are colonized with C. diff. do not develop any infection while others develop severe or recurrent infections. To identify common genetic variants associated with CDI, we performed a genome-wide association analysis in 19,861 participants (1349 cases; 18,512 controls) from the Electronic Medical Records and Genomics (eMERGE) Network. Using logistic regression, we found strong evidence for genetic variation in the DRB locus of the MHC (HLA) II region that predisposes individuals to CDI (P > 1.0 × 10–14; OR 1.56). Altered transcriptional regulation in the HLA region may play a role in conferring susceptibility to this opportunistic enteric pathogen.
Annealing-free fabrication of high-quality indium tin oxide films for free-carrier-based hybrid metal–semiconductor nanophotonics
Authors: Korneluk Alexander , Szymczak Julia , Stefaniuk Tomasz
Published: October 2023

Recent discoveries have revealed that indium tin oxide (ITO), due to the presence of an epsilon-near-zero (ENZ) point and suitable carrier concentration and mobility, can be used to modulate the refractive index, confine fields in the nanoscale, enhance nonlinear effects, achieve ultrafast light switching or to construct so-called time-varying media. While this potential positions ITO as a key material for future nanophotonic devices, producing ITO films with precisely engineered properties remains a significant challenge. Especially when the device’s complex geometry or incorporated materials require the fabrication process to be conducted at substrate temperatures below 100 °C and without any post-annealing treatment. Here we present a comprehensive study on the low-temperature deposition of 70 nm thick ITO films using an e-beam PVD system. The nanolayers evaporated under different conditions were characterized by SEM and AFM microscopy, Hall effect measurement system as well as spectroscopic ellipsometry. We discuss the factors influencing the optical, electrical, and morphological properties of ITO films. We show that smooth nanolayers of similar quality to annealed samples can be obtained at 80 °C by controlling the oxygen plasma parameters, and the ENZ wavelength can be tuned throughout the NIR spectral range. Finally, we show that using the proposed methodology, we fabricated ITO films with resistivity as low as 5.2 × 10–4 Ω cm, smooth surface with RMS < 1 nm, high carrier concentration reaching 1.2 × 1021 cm−3 and high transmittance (85%) in the Vis/NIR spectrum.
Plants forage for soil patches free of plastic pollution but cannot bag the profits
Authors: Speißer Benedikt , van Kleunen Mark
Published: October 2023

Microplastics can affect their surroundings physically and chemically, resulting in diverse effects on plant-soil systems. Similar to other substances (e.g. nutrients and water), microplastics in the environment occur in patches. Such heterogeneous distributions could affect plant responses to plastic pollution. Yet, this has remained untested. We conducted a multispecies experiment including 29 herbaceous plant species and three different microplastic treatments (a control without microplastics, a homogeneous and a heterogeneous microplastic distribution). Based on biomass and root-morphological traits, we assessed how different plastic distributions affect the performance and root-foraging behavior of plants, and whether stronger root foraging is beneficial when microplastics are distributed patchily. Next to general effects on plant productivity and root morphology, we found very strong evidence for root-foraging responses to patchy plastic distributions, with a clear preference for plastic-free patches, resulting in 25% longer roots and 20% more root biomass in the plastic-free patches. Interestingly, however, these foraging responses were correlated with a reduced plant performance, indicating that the benefits of plastic avoidance did not compensate for the associated investments. Our results provide new insights in plant-microplastic interactions and suggest that plants might not just be passively affected by but could also actively respond to environmental plastic pollution.
Alleviation of cadmium and drought stress in wheat by improving growth and chlorophyll contents amended with GA3 enriched deashed biochar
Authors: Anwar Tauseef , Shehzadi Asma , Qureshi Huma , Shah Muhammad Nadeem , Danish Subhan , Salmen Saleh H. , Ansari Mohammad Javed
Published: October 2023

Drought and cadmium (Cd) stress are both major issues that significantly affect the growth and development of wheat plants. Both drought stress and Cd toxicity disrupt physiological processes i.e., nutrient uptake, cell expansion, and enzymatic reactions resulting in poor crop growth. To overcome these issues, the use of activated carbon and gibberellic acid (GA3) are considered valuable amendments. However, the current study aimed to add value using GA3-enriched biochar (GA3-BC). That’s why, a lab experiment was conducted on wheat to assess the effectiveness of GA3-BC against Cd and drought stress. For GA3 enrichment in biochar, 10 µg GA3/g biochar was mixed. There were 3 levels of GA3-BC i.e., 0, 0.6 (GA3-BC1), and 0.9% (GA3-BC). All levels were applied in 3 replicates under no stress (0Cd + no drought), drought stress (DS), and 6 mg Cd/ kg soil (6Cd). Results showed that GA3-BC2 caused a significant improvement in shoot length (44.99%), root length (99.73%), seedling length (60.13%) and shoot fresh weight (63.59%) over control at 6Cd + drought stress. A significant improvement in chlorophyll a, chlorophyll b, and total chlorophyll while a decrease in electrolyte leakage and regulation of antioxidants i.e., lipid peroxidation, SOD, CAT, APx, GR, GPx, GST, and DPHH also signified the effectiveness of GA3-BC2 compared to control at 6Cd + drought stress. In conclusion, GA3-BC2 is an efficacious amendment for simultaneously alleviating drought and Cd stress in wheat. More investigations are recommended at the field level on different cereal crops cultivated in different soil textures to declare GA3-BC2 as the best treatment for mitigation of drought stress and Cd toxicity.
Compressed models for co-reference resolution: enhancing efficiency with debiased word embeddings
Authors: Ioannides Georgios , Jadhav Aishwarya , Sharma Aditi , Navali Samarth , Black Alan W.
Published: October 2023

This work presents a comprehensive approach to reduce bias in word embedding vectors and evaluate the impact on various Natural Language Processing (NLP) tasks. Two GloVe variations (840B and 50) are debiased by identifying the gender direction in the word embedding space and then removing or reducing the gender component from the embeddings of target words, while preserving useful semantic information. Their gender bias is assessed through the Word Embedding Association Test. The performance of co-reference resolution and text classification models trained on both original and debiased embeddings is evaluated in terms of accuracy. A compressed co-reference resolution model is examined to gauge the effectiveness of debiasing techniques on resource-efficient models. To the best of the authors’ knowledge, this is the first attempt to apply compression techniques to debiased models. By analyzing the context preservation of debiased embeddings using a Twitter misinformation dataset, this study contributes valuable insights into the practical implications of debiasing methods for real-world applications such as person profiling.
A conceptual framework for assessing behavioral flexibility of species in response to extreme climatic events
Authors: Ameca Eric I. , Chamart Lucy , Garber Paul A.
Published: October 2023

Inherent differences in the adaptive capacity of species to flexibly respond to extreme climatic events (ECEs) represent a key factor in their survivorship. We introduce and apply a conceptual framework linking knowledge about species’ current ecology and biology with variation in behavioral flexibility to ECEs. We applied it to 199 non-human primate species currently exposed to cyclones across the global tropics. Our findings suggest that species characterized by an increased ability to exploit a broad range of food types, social systems that permit subgrouping, and habitat types that span a range of environmental conditions may have greater success in coping with cyclones than more narrowly constrained or less adaptable primates. Overall, 15% of species, predominantly of the families Atelidae and Cercopithecidae, were assessed as having high or very high flexibility. In contrast, ~ 60% of primates were assessed with low or very low flexibility. These were species mainly belonging to the Cheirogaleidae, Lemuridae, Lepilemuridae, and Indriidae. While much work remains to better understand mechanisms driving differences in behavioral flexibility of species exposed to extreme climate across vertebrate lineages, our framework provides a workable approach that can improve estimates of current vulnerability to these phenomena and better inform conservation and management strategies.
Fuel mixing enhancement of transverse coaxial air and fuel jet by upstream shock wave on in scramjet engines: numerical study
Authors: Abdollahi Seyyed Amirreza , Jafari Moharram , Aminian Saman , Fattahi M. , Uyen P. D.
Published: October 2023

In this study, computational fluid dynamics (CFD) is used to disclose the impacts of upstream shock waves on fuel mixing of cross coaxial air and fuel jet at a scramjet engine. This study has tried to investigate the impact of three different lobe injectors (2-lobe, 3-lobe, and 4-lobe nozzle) on the fuel penetrations along the scramjet combustor. The supersonic air stream is M = 4 while cross hydrogen and air jet are released in sonic velocity. This study uses CFD simulations to analyze the effects of upstream shock waves on fuel mixing in the transverse coaxial jet and assess their potential for improving combustion efficiency. The results demonstrate that the usage of upstream shock waves significantly increases shock interactions and augments the vortex region downstream of the jet. Our results show that the impacts of shock waves on the penetration of fuel jet released from the coaxial lobe nozzle are substantial.
Hemoglobin as a prognostic marker for neurological outcomes in post-cardiac arrest patients: a meta-analysis
Authors: Hou Hongxiang , Pang Li , Zhao Liang , Liu Zuolong , Xing Ji-Hong
Published: October 2023

The aim of this study was to investigate the relationship between serum level of hemoglobin and neurological outcomes following cardiac arrest. Relevant studies were identified by searching electronic databases including PubMed, Web of Science, Cochrane Library, and Embase from June 2012 through April 2023. Articles were rigorously reviewed for their study inclusion and exclusion criteria. Pooled effect date was determined using the standardized mean difference (SMD) and 95% confidence intervals (CI). The Newcastle–Ottawa Scale was used to evaluate study quality. Subgroup analyses were conducted to determine confounding factors affecting patient outcomes. Study heterogeneity, sensitivity, and publication bias were also determined.

This meta-analysis included 11 studies involving 2519 patients. Our results suggest that high serum level of hemoglobin may improve neurological prognosis(SMD = 0.60, 95%CI = 0.49–0.71, I2 = 10.85). The findings of this study indicate that serum level of hemoglobin may be associated with better neurological prognosis, perhaps an appropriate increase in serum haemoglobin levels can improve the neurological prognosis of patients in cardiac arrest.
Predicting survival of advanced laryngeal squamous cell carcinoma: comparison of machine learning models and Cox regression models
Authors: Zhang Yi-Fan , Shen Yu-Jie , Huang Qiang , Wu Chun-Ping , Zhou Liang , Ren Heng-Lei
Published: October 2023

Laryngeal squamous cell carcinoma (LSCC) is a common tumor type. High recurrence rates remain an important factor affecting the survival and quality of life of advanced LSCC patients. We aimed to build a new nomogram and a random survival forest model using machine learning to predict the risk of LSCC progress. The study included 671 patients with AJCC stages III–IV LSCC. To develop a prognostic model, Cox regression analyses were used to assess the relationship between clinic-pathologic factors and disease-free survival (DFS). RSF analysis was also used to predict the DFS of LSCC patients. The ROC curve revealed that the Cox model exhibited good sensitivity and specificity in predicting DFS in the training and validation cohorts (1 year, validation AUC = 0.679, training AUC = 0.693; 3 years, validation AUC = 0.716, training AUC = 0.655; 5 years, validation AUC = 0.717, training AUC = 0.659). Random survival forest analysis showed that N stage, clinical stage, and postoperative chemoradiotherapy were prognostically significant variables associated with survival. The random forest model exhibited better prediction ability than the Cox regression model in the training cohort; however, the two models showed similar prediction ability in the validation cohort.
Combinatorial multimer staining and spectral flow cytometry facilitate quantification and characterization of polysaccharide-specific B cell immunity
Authors: Hoving Dennis , Marques Alexandre H. C. , Huisman Wesley , Nosoh Beckley A. , de Kroon Alicia C. , van Hengel Oscar R. J. , Wu Bing-Ru , Steenbergen Rosanne A. M. , van Helden Pauline M. , Urban Britta C. , Dhar Nisha , Ferreira Daniela M. , Kwatra Gaurav , Hokke Cornelis H. , Jochems Simon P.
Published: October 2023

Bacterial capsular polysaccharides are important vaccine immunogens. However, the study of polysaccharide-specific immune responses has been hindered by technical restrictions. Here, we developed and validated a high-throughput method to analyse antigen-specific B cells using combinatorial staining with fluorescently-labelled capsular polysaccharide multimers. Concurrent staining of 25 cellular markers further enables the in-depth characterization of polysaccharide-specific cells. We used this assay to simultaneously analyse 14 Streptococcus pneumoniae or 5 Streptococcus agalactiae serotype-specific B cell populations. The phenotype of polysaccharide-specific B cells was associated with serotype specificity, vaccination history and donor population. For example, we observed a link between non-class switched (IgM+) memory B cells and vaccine-inefficient S. pneumoniae serotypes 1 and 3. Moreover, B cells had increased activation in donors from South Africa, which has high-incidence of S. agalactiae invasive disease, compared to Dutch donors. This assay allows for the characterization of heterogeneity in B cell immunity that may underlie immunization efficacy.