bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood maltreatment contributes to the medical morbidity of individuals with bipolar disorders
Authors: Godin Ophélia , Leboyer Marion , Grillault Laroche Diane , Aubin Valérie , Belzeaux Raoul , Courtet Philippe , Dubertret Caroline , Gard Sébastien , Haffen Emmanuel , Olie Emilie , Polosan Mircea , Roux Paul , Samalin Ludovic , Schwan Raymund ,   FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE-BD) Collaborators, Bellivier Frank , Etain Bruno
Published: April 2023

Background

Individuals with bipolar disorders (BD) are at risk of premature death, mainly due to medical comorbidities. Childhood maltreatment might contribute to this medical morbidity, which remains underexplored in the literature.

Methods

We assessed 2891 outpatients with BD (according to DSM-IV criteria). Childhood maltreatment was assessed using the Childhood Trauma Questionnaire. Lifetime diagnoses for medical disorders were retrospectively assessed using a systematic interview and checked against medical notes. Medical morbidity was defined by the sum of medical disorders. We investigated associations between childhood maltreatment (neglect and abuse) and medical morbidity while adjusting for potential confounders.

Results

One quarter of individuals had no medical comorbidities, while almost half of them had at least two. Multivariable regression showed that childhood maltreatment (mainly abuse, but also sexual abuse) was associated with a higher medical morbidity. Medical morbidity was also associated with sex, age, body mass index, sleep disturbances, lifetime anxiety disorders and lifetime density of mood episodes. Childhood maltreatment was associated with an increased prevalence of four (i.e. migraine/headache, drug eruption, duodenal ulcer, and thyroid diseases) of the fifteen most frequent medical disorders, however with no difference in terms of age at onset.

Conclusions

This large cross-sectional study confirmed a high medical morbidity in BD and its association with childhood maltreatment. The assessment of childhood maltreatment in individuals with BD should be systematically included in routine care and the potential impact on physical health of psycho-social interventions targeting childhood maltreatment and its consequences should be evaluated.
“The Hidden Life”: Ellen Gates Starr, Vida Dutton Scudder, and Catholic Socialist Progressivism
Authors: Modaff Abigail
Published: April 2023

Ellen Gates Starr and Vida Dutton Scudder are not the best-known names of the Progressive Era. Yet they were at the forefront of progressive reform in the 1880s through the 1910s, and they helped to create the ideas and institutions that defined the settlement house movement. Their prominent historical role demands that we pay serious attention to their alternative visions of progressivism. Starr and Scudder were more politically radical, and more religiously traditional, than many of their peers. Each woman integrated a radical embrace of social transformation with High Church Christian cosmology, creating a Catholic socialist progressivism that contrasts to both other settlement workers and the male leaders of Christian socialism. This article explicates Starr's and Scudder's belief systems and argues for their importance to the history of progressive reform and to the intellectual history of American social change. Although each thinker had her own emphasis—Starr foregrounded art, while Scudder focused on uniting Marxism with Catholicism—Starr, Scudder, and their friendship represent a lost destiny of the progressive movement: a worker-led movement grounded in religious faith.
Maternal protein restriction during the lactation period disrupts the ontogenetic development of behavioral traits in male Wistar rat offspring
Authors: de Oliveira-Silva Juliana , Lisboa Patrícia C. , Lotufo-Denucci Bruna , Fraga Mabel , de Moura Egberto G. , Nunes Fernanda C. , Ribeiro-Carvalho Anderson , Filgueiras Cláudio C. , Abreu-Villaça Yael , Manhães Alex C.
Published: April 2023

Neonatal undernutrition in rats results in short- and long-term behavioral and hormonal alterations in the offspring. It is not clear, however, whether these effects are present since the original insult or if they develop at some specific age later in life. Here, we assessed the ontogenetic profile of behavioral parameters associated with anxiety, exploration and memory/learning of Wistar rat offspring that were subjected to protein malnutrition during lactation. Dams and respective litters were separated into two groups: (1) protein-restricted (PR), which received a hypoproteic chow (8% protein) from birth to weaning [postnatal day (PN) 21]; (2) control (C), which received normoproteic chow. Offspring’s behaviors, corticosterone, catecholamines, T3 and T4 levels were assessed at PN21 (weaning), PN45 (adolescence), PN90 (young adulthood) or PN180 (adulthood). PR offspring showed an age-independent reduction in the levels of anxiety-like behaviors in the Elevated Plus Maze and better memory performance in the Radial Arm Water Maze. PR offspring showed peak exploratory activity in the Open Field earlier in life, at PN45, than C, which showed theirs at PN90. Corticosterone was reduced in PR offspring, particularly at young adulthood, while catecholamines were increased at weaning and adulthood. The current study shows that considerable age-dependent variations in the expression of the observed behaviors and hormonal levels exist from weaning to adulthood in rats, and that protein restriction during lactation has complex variable-dependent effects on the ontogenesis of the assessed parameters.
Rückenschmerzen
Authors: Luomajoki Hannu , Pfeiffer Fabian , Benz Thomas
Published: April 2023

Zusammenfassung. Die Physiotherapie spielt eine zentrale Rolle bei der Prävention und der Behandlung von lumbalen Rückenschmerzen. In der Wissenschaft gibt es keine klaren Hinweise auf die Effektivität einzelner präventiver Massnahmen; Bewegung und aktives Training als zentrale Elemente sind hier jedoch nicht wegzudenken. In der Behandlung von lumbalen Rückenschmerzen ist das Bild jedoch eindeutig: während passive Massnahmen wie Wärme- oder Kälteanwendungen sowie Ultraschall und Elektrotherapie aufgrund der mangelnden Evidenz nicht mehr alleinstehend angewendet werden sollten, zeigt die Kombination von aktiven Übungen und Patientenedukation vielversprechende Erfolge. Werden diese durch vereinzelt eingesetzte manuelle Therapiemassnahmen ergänzt, ergibt sich ein evidenzbasiertes Management von sowohl akuten als auch chronischen lumbalen Rückenschmerzen. Ein Beispiel für eine gelungene Implementierung aktueller Evidenz zur Behandlung von Rückenschmerzen ist GLA:D®, das seit dem Jahr 2021 auch in der Schweiz eingesetzt wird.
Interventionelle Schmerztherapie
Authors: Triebel Jan
Published: April 2023

Zusammenfassung. Die interventionelle Schmerztherapie bei Kreuzschmerzen versteht sich als wichtiges Bindeglied zwischen nichtinvasiven Therapiemassnahmen und operativen Verfahren mit irreversiblen Strukturänderungen. Sie soll (wie auch die anderen Massnahmen) im interdisziplinären Kontext und nicht als Monotherapie zur Anwendung kommen. Diagnostische Infiltrationen können bei der Schmerzlokalisation helfen. Bei akuten Kreuzschmerzen (mit oder ohne radikuläre Symptomatik) kann die interventionelle Schmerztherapie in vielen Fällen eine kurz- bis mittelfristige Beschwerdelinderung bringen. Die interventionelle Schmerztherapie ist eine Subspezialität, welche ein hohes Mass an Erfahrung und Know-how erfordert, welches in der Schweiz mit dem Fähigkeitsausweis SSIPM dokumentiert wird.
Evolution of Global Ocean Tide Levels Since the Last Glacial Maximum
Authors: Sulzbach R. , Klemann V. , Knorr G. , Dobslaw H. , Dümpelmann H. , Lohmann G. , Thomas M.
Published: April 2023

This study addresses the evolution of global tidal dynamics since the Last Glacial Maximum focusing on the extraction of tidal levels that are vital for the interpretation of geologic sea‐level markers. For this purpose, we employ a truly‐global barotropic ocean tide model which considers the non‐local effect of Self‐Attraction and Loading. A comparison to a global tide gauge data set for modern conditions yields agreement levels of 65%–70%. As the chosen model is data‐unconstrained, and the considered dissipation mechanisms are well understood, it does not have to be re‐tuned for altered paleoceanographic conditions. In agreement with prior studies, we find that changes in bathymetry during glaciation and deglaciation do exert critical control over the modeling results with minor impact by ocean stratification and sea ice friction. Simulations of 4 major partial tides are repeated in time steps of 0.5–1 ka and augmented by 4 additional partial tides estimated via linear admittance. These are then used to derive time series from which the tidal levels are determined and provided as a global data set conforming to the HOLSEA format. The modeling results indicate a strengthened tidal resonance by M2, but also by O1, under glacial conditions, in accordance with prior studies. Especially, a number of prominent changes in local resonance conditions are identified, that impact the tidal levels up to several meters difference. Among other regions, resonant features are predicted for the North Atlantic, the South China Sea, and the Arctic Ocean.
Air‐Sea Fluxes of CO2 in the Indian Ocean Between 1985 and 2018: A Synthesis Based on Observation‐Based Surface CO2, Hindcast and Atmospheric Inversion Models
Authors: Sarma V. V. S. S. , Sridevi B. , Metzl N. , Patra P. K. , Lachkar Z. , Chakraborty Kunal , Goyet C. , Levy M. , Mehari M. , Chandra N.
Published: April 2023

The Indian Ocean significantly influences the global carbon cycle but it is one of the undersampled regions with reference to surface ocean pCO2. As a part of the Regional Carbon Cycle Assessment and Processes‐2 (RECCAP2) project, several approaches, such as interpolated observational climatology, hindcast model, observation‐based surface CO2 (empirical models), and atmospheric inversion models have been employed for estimating net sea‐to‐air CO2 fluxes between 1985 and 2018. The seasonal, spatial and long‐term variability in sea‐to‐air fluxes of CO2 were compared with observational climatology. The mean value of CO2 in the Indian Ocean (north of 37.5°S) for the period of 1985–2018 using all models is estimated to be −0.19 ± 0.1 PgC yr−1 and it is consistent with the observational climatology (−0.07 ± 0.14 PgC yr−1). The Indian Ocean north of 18°S is found to be the mean annual source (0.04 ± 0.05 PgC yr−1) whereas a net sink (−0.23 ± 0.11 PgC yr−1) in the south of 18°S. All models captured observed spatial patterns but underestimated the net source of CO2 in the Oman/Somalia upwelling, the Equatorial Indian Ocean and the Bay of Bengal whereas CO2 sink is overestimated in the South Indian Ocean. Overall, all models captured the seasonality in pCO2 levels and CO2 fluxes but overestimated the amplitude of their variability. All models suggested the strengthening of the sink over the period between 1985 and 2018 by 0.02 PgC yr−1 decade−1. A significant increase in the collection of surface ocean pCO2 and atmospheric CO2 measurements improves the model simulations in the Indian Ocean.
Diverging Northern Hemisphere Trends in Meteorological Versus Ecological Indicators of Spring Onset in CMIP6
Authors: Li Xiaolu , Ault Toby , Evans Colin P. , Lehner Flavio , Carrillo Carlos M. , Donnelly Alison , Crimmins Theresa , Gallinat Amanda S. , Schwartz Mark D.
Published: April 2023

Plant phenology regulates the carbon cycle and land‐atmosphere coupling. Currently, climate models often disagree with observations on the seasonal cycle of vegetation growth, partially due to how spring onset is measured and simulated. Here we use both thermal and leaf area index (LAI) based indicators to characterize spring onset in CMIP6 models. Although the historical timing varies considerably across models, most agree that spring has advanced in recent decades and will continue to arrive earlier with future warming. Across the Northern Hemisphere for the periods 1950–2014, 1981–2014, and 2015–2099 in the historical and SSP5‐8.5 simulations, thermal‐based indicators estimate spring advances of −0.7 ± 0.2, −1.4 ± 0.4, and −2.4 ± 0.7 days/decade, while LAI‐based indicators estimate −0.4 ± 0.3, −0.1 ± 0.3, and −1±1.1 days/decade. Thereby, LAI‐based indicators exhibit weaker trends toward earlier onset, leading to uncertainties from different indices being as large or larger than model uncertainty. Reconciling these discrepancies is critical for understanding future changes in spring onset.
Simulations of Halos Produced by Carbon Dioxide Ice Crystals in the Martian Atmosphere
Authors: Ding Jiachen , Yang Ping , Lemmon Mark T. , Zhang Yuheng
Published: April 2023

It has been known for decades that carbon dioxide (CO2) ice clouds exist in the Martian atmosphere. According to remote sensing observations and previous modeling studies, the Martian CO2 ice crystals may be sufficiently large to generate halos. However, observations of CO2 ice crystal halos have not been reported so far. This study simulates the scattering and polarized phase functions at a wavelength of 0.48 μm based on state‐of‐the‐art light‐scattering computational capabilities. The specific CO2 ice crystal habits considered in the simulations include cubes, octahedrons, cubo‐octahedrons, and truncated octahedrons of various sizes. The halos produced by CO2 ice crystals peak at approximately 29° and 42°. Moreover, large CO2 ice crystals may cause strong scattering peaks at 155° and 180°. An ensemble of water (H2O) ice crystals and CO2 ice crystals with appropriate mixing fractions might be responsible for a halo occurrence recently observed on Mars.
Solar Hysteresis Pattern and Spectral Components in TEC Time Series (GPS and TIE‐GCM) of the Quadrilaterally Coupled Geomagnetic Conjugate Low‐Latitude Stations
Authors: Rao S. S. , Chakrabarty D. , Srivastava Nandita
Published: April 2023

The current study is a first‐of‐its‐kind in that it compares the Total Electron Content (TEC) of the solar cycle from the Global Positioning System (GPS) and Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model (TIE‐GCM) over the geomagnetically conjugate low‐latitude stations with the particular scenario of lower atmospheric conditions over land‐ and sea‐locked locations. For this, TEC data for the period 2009–2017 is used from northern hemispheric stations Varanasi (25.31°N; 82.97°E) and LHAZ (29.65°N; 91.10°E) and southern hemispheric stations DGAR (7.27°S; 72.37°E) and COCO Island (12.18°S; 96.83°E). The solar cycle variation in TEC is identified by two distinct maxima and hysteresis between the ascending and descending phases. The solar cycle trends are modulated by the equatorial ionization anomaly as well as longitudinal biases. The Lomb‐Scargle periodogram shows that the improved TIE‐GCM version 2.0, which incorporates variable eddy diffusion to provide an accurate simulation of seasonal variability, is largely successful in simulating semi‐annual and annual oscillations but still needs to resolve the seasonal anomaly feature, particularly in the case of southern low latitude stations. Terannual (120‐day) and 1.4‐year (500‐day) periodicities in the TEC time series are observed only at EIA region stations, not at off‐crest location LHAZ, and are most likely caused by E x B drift. The wavelet coherence analysis reveals that the Quasi Biannual Oscillations (QBO) in the TEC time series (597‐, 773‐, and 930‐day) have a strong physical affinity with the QBO oscillation of F10.7 flux. Results indicate that both solar activity and equatorial electrodynamics significantly influence the QBO oscillation in the TEC.
The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome
Authors: Külp Marius , Larghero Patrizia , Alten Julia , Cario Gunnar , Eckert Cornelia , Caye-Eude Aurélie , Cavé Hélène , Schmachtel Tessa , Bardini Michela , Cazzaniga Giovanni , De Lorenzo Paola , Valsecchi Maria Grazia , Bonig Halvard , Meyer Claus , Rieger Michael A. , Marschalek Rolf
Published: April 2023

KMT2A-rearranged acute lymphoblastic infant leukemia (KMT2A-r iALL) is associated with outsize risk of relapse and relapse mortality. We previously reported strong upregulation of the immediate early gene EGR3 in KMT2A::AFF1 iALL at relapse; now we provide analyses of the EGR3 regulome, which we assessed through binding and expression target analysis of an EGR3-overexpressing t(4;11) cell culture model. Our data identify EGR3 as a regulator of early B-lineage commitment. Principal component analysis of 50 KMT2A-r iALL patients at diagnosis and 18 at relapse provided strictly dichotomous separation of patients based on the expression of four B-lineage genes. Absence of B-lineage gene expression translates to more than two-fold poorer long-term event-free survival. In conclusion, our study presents four B-lineage genes with prognostic significance, suitable for gene expression-based risk stratification of KMT2A-r iALL patients.
Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex
Authors: Cai Sihui , Zhang Chenqiu , Zhuang Zhen , Zhang Shengnan , Ma Ling , Yang Shuai , Zhou Tao , Wang Zheyu , Xie Weihong , Jin Shouheng , Zhao Jincun , Guan Xiangdong , Wu Jianfeng , Cui Jun , Wu Yaoxing
Published: April 2023

Currently, the incidence and fatality rate of SARS-CoV-2 remain continually high worldwide. COVID-19 patients infected with SARS-CoV-2 exhibited decreased type I interferon (IFN-I) signal, along with limited activation of antiviral immune responses as well as enhanced viral infectivity. Dramatic progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing pathways. However, it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during infection. In the current study, we figure out that SARS-CoV-2 infection leads to the accumulation of released mitochondria DNA (mtDNA), which in turn triggers cGAS to activate IFN-I signaling. As countermeasures, SARS-CoV-2 nucleocapsid (N) protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I signaling. Mechanically, N protein disrupts the assembly of cGAS with its co-factor G3BP1 by undergoing DNA-induced liquid-liquid phase separation (LLPS), subsequently impairs the double-strand DNA (dsDNA) detection ability of cGAS. Taken together, our findings unravel a novel antagonistic strategy by which SARS-CoV-2 reduces DNA-triggered IFN-I pathway through interfering with cGAS-DNA phase separation.
Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis
Authors: Wu Yutong , Ai Hongbo , Xi Yuhang , Yin Pengbin , Qu Ying , Xu Jianzhong , Dou Ce , Luo Fei
Published: April 2023

Osteoporosis is associated with excessive activity of osteoclasts. In bone turn over, most osteoclasts undergo apoptosis after bone resorption and produce a large number of apoptotic bodies (ABs). However, the biological function of osteoclast-derived apoptotic bodies (OC-ABs) in the progression of osteoporosis is still unknow. In our study, we identified a reduction of OC-AB quantity in the bone marrow cavity during the progression of osteoporosis, an apoptotic body-deficient MRL/lpr mice were used to study the pro-osteogenic ability of OC-ABs. Mechanistically, OC-ABs promote osteogenesis of bone mesenchymal stem cells (BMSCs) by activating the downstream mTOR pathway via RANKL-mediated reverse signaling. Moreover, systemic infusion of exogenous OC-ABs effectively delayed the bone loss in ovariectomized (OVX) mice, validated the role of OC-ABs as bone protective factor in the pathogenesis of osteoporosis. Taken together, our study elucidates the biological function of OC-ABs in the pathological progression of osteoporotic bone loss and suggests a potential therapeutic strategy to delay bone loss.
Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM
Authors: Saotome Kei , Dudgeon Drew , Colotti Kiersten , Moore Michael J. , Jones Jennifer , Zhou Yi , Rafique Ashique , Yancopoulos George D. , Murphy Andrew J. , Lin John C. , Olson William C. , Franklin Matthew C.
Published: April 2023

The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length α/β TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230–239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230–239) peptide and the closely related MAGEA8 (232–241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions.
Sequence-structure-function relationships in the microbial protein universe
Authors: Koehler Leman Julia , Szczerbiak Pawel , Renfrew P. Douglas , Gligorijevic Vladimir , Berenberg Daniel , Vatanen Tommi , Taylor Bryn C. , Chandler Chris , Janssen Stefan , Pataki Andras , Carriero Nick , Fisk Ian , Xavier Ramnik J. , Knight Rob , Bonneau Richard , Kosciolek Tomasz
Published: April 2023

For the past half-century, structural biologists relied on the notion that similar protein sequences give rise to similar structures and functions. While this assumption has driven research to explore certain parts of the protein universe, it disregards spaces that don’t rely on this assumption. Here we explore areas of the protein universe where similar protein functions can be achieved by different sequences and different structures. We predict ~200,000 structures for diverse protein sequences from 1,003 representative genomes across the microbial tree of life and annotate them functionally on a per-residue basis. Structure prediction is accomplished using the World Community Grid, a large-scale citizen science initiative. The resulting database of structural models is complementary to the AlphaFold database, with regards to domains of life as well as sequence diversity and sequence length. We identify 148 novel folds and describe examples where we map specific functions to structural motifs. We also show that the structural space is continuous and largely saturated, highlighting the need for a shift in focus across all branches of biology, from obtaining structures to putting them into context and from sequence-based to sequence-structure-function based meta-omics analyses.
Cell surface-localized CsgF condensate is a gatekeeper in bacterial curli subunit secretion
Authors: Swasthi Hema M. , Basalla Joseph L. , Dudley Claire E. , Vecchiarelli Anthony G. , Chapman Matthew R.
Published: April 2023

Curli are functional amyloids present on the outer membrane of E. coli. CsgF is required for the proper assembly of curli. Here, we found that the CsgF phase separates in vitro and that the ability of CsgF variants to phase-separate is tightly correlated with CsgF function during curli biogenesis. Substitution of phenylalanine residues in the CsgF N-terminus both reduced the propensity of CsgF to phase-separate and impaired curli assembly. Exogenous addition of purified CsgF complemented csgF − cells. This exogenous addition assay was used to assess the ability of CsgF variants to complement csgF ‒ cells. CsgF on the cell surface modulated the secretion of CsgA, the curli major subunit, to the cell surface. We also found that the CsgB nucleator protein can form SDS-insoluble aggregates within the dynamic CsgF condensate. We propose that these multicomponent CsgF-B condensates form a nucleation-competent complex that templates CsgA amyloid formation on the cell surface.
Designing tailored combinations of structural units in polymer dielectrics for high-temperature capacitive energy storage
Authors: Wang Rui , Zhu Yujie , Fu Jing , Yang Mingcong , Ran Zhaoyu , Li Junluo , Li Manxi , Hu Jun , He Jinliang , Li Qi
Published: April 2023

Many mainstream dielectric energy storage technologies in the emergent applications, such as renewable energy, electrified transportations and advanced propulsion systems, are usually required to operate under harsh-temperature conditions. However, excellent capacitive performance and thermal stability tend to be mutually exclusive in the current polymer dielectric materials and applications. Here, we report a strategy to tailor structural units for the design of high-temperature polymer dielectrics. A library of polyimide-derived polymers from diverse combinations of structural units are predicted, and 12 representative polymers are synthesized for direct experimental investigation. This study provides important insights into decisive structural factors necessary to achieve robust and stable dielectrics with high energy storage capabilities at elevated temperature. We also find that the high-temperature insulation performance would experience diminishing marginal utility as the bandgap increases beyond a critical point, which is strongly correlated to the dihedral angle between neighboring planes of conjugation in these polymers. By experimentally testing the optimized and predicted structures, an increased energy storage at temperatures up to 250 °C is observed. We discuss the possibility for this strategy to be generally applied to other polymer dielectrics to achieve further performance enhancement.
Importance of incorporating spatial and temporal variability of biomass yield and quality in bioenergy supply chain
Authors: Roni Mohammad S. , Lin Yingqian , Hartley Damon S. , Thompson David N. , Hoover Amber N. , Emerson Rachel M.
Published: April 2023

Biofuels made from biomass and waste residues will largely contribute to United States’ 2050 decarbonization goal in the aviation sector. While cellulosic biofuels have the potential fuel performance equivalent to petroleum-based jet fuel, the biofuel industry needs to overcome the supply chain barrier caused by temporal and spatial variability of biomass yield and quality. This study highlights the importance of incorporating spatial and temporal variability during biomass supply chain planning via optimization modeling that incorporates 10 years of drought index data, a primary factor contributing to yield and quality variability. The results imply that the cost of delivering biomass to biorefinery may be significantly underestimated if the multi-year temporal and spatial variation in biomass yield and quality is not captured. For long term sustainable biorefinery operations, the industry should optimize supply chain strategy by studying the variability of yield and quality of biomass in their supply sheds.
Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients
Authors: Klussmann Jens Peter , Grosheva Maria , Meiser Peter , Lehmann Clara , Nagy Eszter , Szijártó Valéria , Nagy Gábor , Konrat Robert , Flegel Michael , Holzer Frank , Groß Dorothea , Steinmetz Charlotte , Scherer Barbara , Gruell Henning , Schlotz Maike , Klein Florian , de Aragão Paula Aguiar , Morr Henning , Al Saleh Helal , Bilstein Andreas , Russo Belisa , Müller-Scholtz Susanne , Acikel Cengizhan , Sahin Hacer , Werkhäuser Nina , Allekotte Silke , Mösges Ralph
Published: April 2023

With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients’ status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine’s potential as an antiviral treatment.

Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.
Never in mitosis gene A-related kinase-8 promotes proliferation, migration, invasion, and stemness of breast cancer cells via β-catenin signalling activation
Authors: Kang Eunji , Kim Hong-Kyu , Lee Han-Byoel , Han Wonshik
Published: April 2023

Never in mitosis gene A (NIMA)-related kinase-8 (NEK8) is involved in cell cycle progression, cytoskeleton development, and DNA damage repair. However, its role in breast cancer has not yet been explored. To investigate this, NEK8 was knocked down in MDA-MB-231, BT549, and HCC38 breast cancer cell lines. We observed a decrease in cell proliferation and colony formation owing to regulation of the G1/S and G2/M transitions. Furthermore, the expression of several cell cycle regulatory proteins was altered, including that of cyclin D1, cyclin B1, CDK4, CDK2, and surviving. NEK8 knockdown impaired cell migration and invasion as well as reduced the expression of epithelial-mesenchymal transition markers. Regarding stem-cell characteristics, NEK8 knockdown decreased the tumour sphere formation, aldehyde dehydrogenase activity, and stem-cell marker expression, including that of CD44, Sox2, Oct4a, and Nanog. Further analysis revealed that NEK8 interacts with β-catenin. Also, NEK8 knockdown promoted β-catenin degradation. NEK8-silenced MDA-MB-231 cells inhibited xenograft tumour growth, metastasis, and tumour initiation in vivo. Using the Oncomine and TNMplot public databases, we found a significant correlation between NEK8 overexpression and poor clinical outcomes in breast cancer patients. Thus, NEK8 may be a crucial regulator of breast cancer progression and a potential therapeutic target.
Prevalence and incidence of stroke in Latin America and the Caribbean: a systematic review and meta-analysis
Authors: Cagna-Castillo Diego , Salcedo-Carrillo A. Lucia , Carrillo-Larco Rodrigo M. , Bernabé-Ortiz Antonio
Published: April 2023

Stroke is a recurrent and well-known cardiovascular event and a leading cause of death worldwide. We identified reliable epidemiological evidence of stroke in Latin America and the Caribbean (LAC) and estimated the prevalence and incidence of stroke, overall and by sex, in that region. A systematic search in OVID (Medline, Embase and Global Health) and in the Latin America and Caribbean Health Sciences Literature (LILACS) until the end of 2020 was made for all cross-sectional or longitudinal studies estimating (or allowing the estimation of) the prevalence or incidence of stroke among individuals of the general population ≥ 18 years from LAC countries. No language restriction was applied. Studies were assessed for methodological quality and risk of bias. Pooled estimates were calculated using random effect meta-analysis as high heterogeneity was expected. A total of 31 papers for prevalence and 11 papers for incidence were included in the review for analysis. The overall pooled stroke prevalence was 32 (95% CI 26–38) per 1000 subjects and were similar among men (21; 95% CI 17–25) and women (20; 95% CI 16–23) per 1000 subjects. The overall pooled stroke incidence was 255 (95% CI 217–293) per 100 000 person-years, being higher in men (261; 95% CI 221–301) compared to women (217; 95% CI 184–250) per 100 000 person-years. Our results highlight the relevance of the prevalence and incidence of stroke in the LAC region. The estimates were similar in stroke prevalence by sex, but with higher incidence rates among males than females. Subgroup analyses highlight the need for standardized methodologies to obtain appropriate prevalence and incidence estimates at the population level in a region with a great burden of cardiovascular events.
Evidence for unconventional superconductivity and nontrivial topology in PdTe
Authors: Chapai Ramakanta , Reddy P. V. Sreenivasa , Xing Lingyi , Graf David E. , Karki Amar B. , Chang Tay-Rong , Jin Rongying
Published: April 2023

PdTe is a superconductor with Tc ~ 4.25 K. Recently, evidence for bulk-nodal and surface-nodeless gap features has been reported in PdTe. Here, we investigate the physical properties of PdTe in both the normal and superconducting states via specific heat and magnetic torque measurements and first-principles calculations. Below Tc, the electronic specific heat initially decreases in T3 behavior (1.5 K < T < Tc) then exponentially decays. Using the two-band model, the superconducting specific heat can be well described with two energy gaps: one is 0.372 meV and another 1.93 meV. The calculated bulk band structure consists of two electron bands (α and β) and two hole bands (γ and η) at the Fermi level. Experimental detection of the de Haas-van Alphen (dHvA) oscillations allows us to identify four frequencies (Fα = 65 T, Fβ = 658 T, Fγ = 1154 T, and Fη = 1867 T for H // a), consistent with theoretical predictions. Nontrivial α and β bands are further identified via both calculations and the angle dependence of the dHvA oscillations. Our results suggest that PdTe is a candidate for unconventional superconductivity.
Adsorption of radon on silver exchanged zeolites at ambient temperatures
Authors: Heinitz Stephan , Mermans Jasper , Maertens Dominic , Skliarova Hanna , Aerts Alexander , Cardinaels Thomas , Gueibe Christophe , Rutten Jos , Ireland Natalie , Kuznicki Daniel , Kuznicki Steven
Published: April 2023

Since more than 100 years, the adsorption of the radioactive noble gas radon (222Rn) is performed on activated charcoal at cryogenic temperatures. There is little—if any—progress in the field of radon adsorption at ambient conditions to facilitate the development of simple and compact radon adsorption systems. We report here on the truly remarkable property of the synthetic silver-exchanged zeolites Ag-ETS-10 and Ag-ZSM-5 to strongly adsorb radon gas at room temperature. 222Rn breakthrough experiments in nitrogen carrier gas have shown that these materials exhibit radon adsorption coefficients exceeding 3000 m3/kg at 293 K, more than two orders of magnitude larger than any noble gas adsorbent known to date. Water vapor and carrier gas type were found to strongly influence radon adsorption, practically qualifying these silver exchanged materials as a new class of radon adsorbents. Our results demonstrate that Ag-ETS-10 and Ag-ZSM-5 are materials that show high affinity towards radon gas at ambient temperatures making them candidate materials for environmental and industrial 222Rn mitigation applications. Adsorption systems based on silver loaded zeolites have the potential to replace activated charcoal as material of choice in many radon related research areas by avoiding the necessity of cryogenic cooling.
The aorta in humans and African great apes, and cardiac output and metabolic levels in human evolution
Authors: Ríos Luis , Sleeper Meg M. , Danforth Marietta D. , Murphy Hayley Weston , Kutinsky Ilana , Rosas Antonio , Bastir Markus , Gómez-Cambronero José , Sanjurjo Ricardo , Campens Laurence , Rider Oliver , Pastor Francisco
Published: April 2023

Humans have a larger energy budget than great apes, allowing the combination of the metabolically expensive traits that define our life history. This budget is ultimately related to the cardiac output, the product of the blood pumped from the ventricle and the number of heart beats per minute, a measure of the blood available for the whole organism physiological activity. To show the relationship between cardiac output and energy expenditure in hominid evolution, we study a surrogate measure of cardiac output, the aortic root diameter, in humans and great apes. When compared to gorillas and chimpanzees, humans present an increased body mass adjusted aortic root diameter. We also use data from the literature to show that over the human lifespan, cardiac output and total energy expenditure follow almost identical trajectories, with a marked increase during the period of brain growth, and a plateau during most of the adult life. The limited variation of adjusted cardiac output with sex, age and physical activity supports the compensation model of energy expenditure in humans. Finally, we present a first study of cardiac output in the skeleton through the study of the aortic impression in the vertebral bodies of the spine. It is absent in great apes, and present in humans and Neanderthals, large-brained hominins with an extended life cycle. An increased adjusted cardiac output, underlying higher total energy expenditure, would have been a key process in human evolution.
Reliability analysis of the compressed air supplying system in underground mines
Authors: Rahimdel Mohammad Javad , Ghodrati Behzad
Published: April 2023

Despite the high cost and low efficiency, compressed air is mostly used in underground mining for ore extraction, hoisting, and mineral processing operations. Failures of compressed air systems not only threaten the health and safety of workers but also contribute to inefficient control of airflow and stopped all equipment that operates by compressed air. In such uncertain conditions, mine managers are faced with the big challenge to supply enough compressed air, and therefore, the reliability evaluation of these systems is essential. This paper aims to analyze the reliability of the compressed air system using the Markov modeling approach as a case study, Qaleh-Zari Copper Mine, Iran. To achieve this, the state space diagram was constructed considering all relevant states for all compressors in the main compressor house of the mine. The failure and repair rate of all main and reserve compressors were calculated for all possible transitions between states to obtain the probability of being of the system in each of the states. Moreover, the probability of failure at any time period was considered to study the reliability behavior. The results of this study show that there is 31.5% probability that the compressed air supplying system is in operating condition with two main and one standby compressors. The system probability that two main compressors are remain in the operation without failure for one months is 92.32%. Furthermore, the lifetime of the system is estimated 33 months when at least one main compressor is active.
Antagonistic fatigue crack acceleration/deceleration phenomena in Ni-based superalloy 718 under hydrogen-supply
Authors: Takakuwa Osamu , Ogawa Yuhei , Miyata Ryunosuke
Published: April 2023

Mechanical properties of structural alloys, including Ni-based superalloy 718 (Alloy718), are degraded when hydrogen (H) is supplied: hydrogen embrittlement (HE). The presence of H notably deteriorates fatigue crack growth (FCG) property, which renders the growth rate much higher and shortens the lifetime of the components operating in the hydrogenating environment. Hence, the mechanisms behind such acceleration phenomenon in FCG should be understood comprehensively toward developing promising alloys resistant to hydrogen occlusion. In particular, Alloy718 has a meager resistance to HE, even regularly displaying superior mechanical and physical performances. Notwithstanding, the present study unveiled that the FCG acceleration by dissolved H in Alloy718 can be negligible. An abnormal deceleration of FCG can instead be pronounced by optimizing the metallurgical state, a hopeful prospect in Ni-based alloys applied to the hydrogenating environment.
Imaging the subsurface architecture in porphyry copper deposits using local earthquake tomography
Authors: Comte Diana , Palma Gisella , Vargas Jimena , Calle-Gardella Daniela , Peña Matías , García-Fierro Sergio , D’Andres Joëlle , Roecker Steven , Pichott Sergio
Published: April 2023

An essential part of the world's remaining mineral resources is expected to reside deep in the crust or under post-mineralization cover. For porphyry copper deposits, the world’s primary source of Cu, Mo, and Re, identifying the dynamic processes that control their emplacement in the upper crust can guide future exploration. Seismic tomography can constrain these processes through imaging deep-seated structures at the regional scale. Here we construct a three-dimensional model of the Vp/Vs ratio, based on arrival times of P and S seismic waves, beneath the Cerro Colorado porphyry Cu–(Mo) deposit in northern Chile. Our images show that low Vp/Vs (~ 1.55–1.65) anomalies, extending to ~ 5–15 km depth, coincide with the surface expression of known porphyry copper deposits and prospects, as well as delimit structures that host orebodies and related hydrothermal alteration zones. Medium Vp/Vs (~ 1.68–1.74) and high Vp/Vs (Vp/Vs ~ 1.85) bodies correspond to intermediate-felsic plutonic precursors for porphyry intrusions and mafic magma reservoirs that underlie shallower orebodies, respectively. Imaging these precursor and parental plutons is crucial to the identification of orebodies as they act as the source of fluids for porphyry copper generation. This study demonstrates the potential of local earthquake tomography as a tool to identify future deep mineral resources with minimal environmental impact.
Factors associated with adverse drug reactions or death in very elderly hospitalized patients with pulmonary tuberculosis
Authors: Yagi Mitsuaki , Shindo Yuichiro , Mutoh Yoshikazu , Sano Masahiro , Sakakibara Toshihiro , Kobayashi Hironori , Matsuura Akinobu , Emoto Ryo , Matsui Shigeyuki , Nakagawa Taku , Ogawa Kenji
Published: April 2023

The aging of patients with tuberculosis and better therapeutic management for them are recent concerns. This study aimed to identify risk factors for adverse drug reactions (ADRs) or death in very elderly patients with pulmonary tuberculosis and to assess the association between the dosage of antituberculosis drugs and outcomes. We conducted a multicenter retrospective study at two hospitals. Hospitalized patients (≥ 80 years old) with pulmonary tuberculosis who were treated with antituberculosis drugs were enrolled. Multivariate analysis was performed to assess factors associated with ADRs or death within 60 days after treatment initiation. In total, 632 patients were included. The primary endpoint occurred in 268 patients (190 ADRs and 78 deaths). A serum albumin level < 2.5 g/dL, respiratory failure, and dependent activities of daily living were independent risk factors for ADRs or death. However, a low dosage (< 8 mg/kg/day) of rifampicin was associated with a lower risk of the primary outcomes. Delayed time to negative sputum culture conversion was not observed in the lower dosage of rifampicin group. Very elderly hospitalized tuberculosis patients with the aforementioned risk factors should be carefully monitored to receive safer treatment. Rifampicin dosage reduction may be considered for very elderly tuberculosis patients to prevent ADRs/death.
Complete remission in children and adolescents with type 1 diabetes mellitus—prevalence and factors
Authors: Podolakova Kristina , Barak Lubomir , Jancova Emilia , Tarnokova Simona , Podracka Ludmila , Dobiasova Zuzana , Skopkova Martina , Gasperikova Daniela , Stanik Juraj
Published: April 2023

Little is known about complete remission in Type 1 diabetes mellitus (T1D) with the discontinuance of insulin treatment for a period of time. In this retrospective study we analysed the frequency and factors of onset and duration of 1. remission and 2. complete remission in children and adolescents with T1D from the Children Diabetes Centre in Bratislava, Slovakia. A total of 529 individuals with T1D, aged < 19 years (8.5 ± 4.3 years) at diabetes onset were included in the study. Remission was defined by HbA1c < 7.0% (53 mmol/mol) and an insulin daily dose < 0.5 IU/kg (and 0 IU/kg for complete remission). Remission occurred in 210 (39.7%) participants, and 15 of them had complete remission (2.8% from all participants). We have identified a new independent factor of complete remission onset (higher C-peptide). Complete remitters had a longer duration of remission compared with other remitters and also differed in lower HbA1c levels. No association was seen with autoantibodies or genetic risk score for T1D. Thus, not only partial but also complete remission is influenced by factors pointing toward an early diagnosis of T1D, which is important for better patient outcome.
Microvascular and oxidative stress responses to acute high-altitude exposure in prematurely born adults
Authors: Manferdelli Giorgio , Narang Benjamin J. , Pialoux Vincent , Giardini Guido , Debevec Tadej , Millet Grégoire P.
Published: April 2023

Premature birth is associated with endothelial and mitochondrial dysfunction, and chronic oxidative stress, which might impair the physiological responses to acute altitude exposure. We assessed peripheral and oxidative stress responses to acute high-altitude exposure in preterm adults compared to term born controls. Post-occlusive skeletal muscle microvascular reactivity and oxidative capacity from the muscle oxygen consumption recovery rate constant (k) were determined by Near-Infrared Spectroscopy in the vastus lateralis of seventeen preterm and seventeen term born adults. Measurements were performed at sea-level and within 1 h of arrival at high-altitude (3375 m). Plasma markers of pro/antioxidant balance were assessed in both conditions. Upon acute altitude exposure, compared to sea-level, preterm participants exhibited a lower reperfusion rate (7 ± 31% vs. 30 ± 30%, p = 0.046) at microvascular level, but higher k (6 ± 32% vs. −15 ± 21%, p = 0.039), than their term born peers. The altitude-induced increases in plasma advanced oxidation protein products and catalase were higher (35 ± 61% vs. −13 ± 48% and 67 ± 64% vs. 15 ± 61%, p = 0.034 and p = 0.010, respectively) and in xanthine oxidase were lower (29 ± 82% vs. 159 ± 162%, p = 0.030) in preterm compared to term born adults. In conclusion, the blunted microvascular responsiveness, larger increases in oxidative stress and skeletal muscle oxidative capacity may compromise altitude acclimatization in healthy adults born preterm.
Self-emergent vortex flow of microtubule and kinesin in cell-sized droplets under water/water phase separation
Authors: Sakuta Hiroki , Nakatani Naoki , Torisawa Takayuki , Sumino Yutaka , Tsumoto Kanta , Oiwa Kazuhiro , Yoshikawa Kenichi
Published: April 2023

By facilitating a water/water phase separation (w/wPS), crowded biopolymers in cells form droplets that contribute to the spatial localization of biological components and their biochemical reactions. However, their influence on mechanical processes driven by protein motors has not been well studied. Here, we show that the w/wPS droplet spontaneously entraps kinesins as well as microtubules (MTs) and generates a micrometre-scale vortex flow inside the droplet. Active droplets with a size of 10–100 µm are generated through w/wPS of dextran and polyethylene glycol mixed with MTs, molecular-engineered chimeric four-headed kinesins and ATP after mechanical mixing. MTs and kinesin rapidly created contractile network accumulated at the interface of the droplet and gradually generated vortical flow, which can drive translational motion of a droplet. Our work reveals that the interface of w/wPS contributes not only to chemical processes but also produces mechanical motion by assembling species of protein motors in a functioning manner.