bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydro‐Mechanical Interactions of a Rock Slope With a Retreating Temperate Valley Glacier
Authors: Hugentobler Marc , Aaron Jordan , Loew Simon , Roques Clément
Published: March 2022

Rock slope failures often result from progressive rock mass damage which accumulates over long timescales. In deglaciating environments, rock slopes are affected by stress perturbations driven by mechanical unloading due to ice downwasting and concurrent changes in thermal and hydraulic boundary conditions. Since in‐situ data are rare, the different processes and their relative contribution to slope damage remain poorly understood. Here, we analyze borehole monitoring data from a rock slope adjacent to the retreating Great Aletsch Glacier (Switzerland) and compare it to englacial water levels, climate data, and decreasing ice levels. Rock slope pore pressures show a seasonal signal controlled by infiltration events as well as effects from the connectivity to the englacial hydrological system. We find that reversible and irreversible strains are driven by: (a) hydromechanical effects caused by englacial pressure fluctuations and infiltration events, (b) stress transfer related to changing mechanical glacial loads from short‐term englacial water level fluctuations and longer term ice downwasting, and (c) thermomechanical effects from annual temperature cycles penetrating the shallow subsurface, which primarily result in reversible deformation. We relate most observed irreversible strain (damage) to mechanical unloading from ice downwasting. Damage is strongest directly at the ice margin and moves through the slope at the pace of glacial retreat and advance. Locations with many retreat/advance cycles are very sensitive to landslide formation. The current climate warming impacts very sensitive valley sectors, which is confirmed by landslide distributions and activity in the study area.
Space Weathering of the Chang'e‐5 Lunar Sample From a Mid‐High Latitude Region on the Moon
Authors: Gu Lixin , Chen Yongjin , Xu Yuchen , Tang Xu , Lin Yangting , Noguchi Takaaki , Li Jinhua
Published: March 2022

Micrometeorite impacts and solar wind irradiation, the dominant space weathering (SW) processes, largely modified compositions and microtexture of soil materials on the Moon. Here, we report the SW characteristics of the Chang'e‐5 lunar soils from mid‐high latitude (43.06°N). All mineral phases exposed on the surface of a single basalt clast have a vapor deposit layer, whereas the textures of the solar wind irradiation‐damaged zone are dependent on the host mineral species. Nanophase Fe (npFe0) particles are spherical in the amorphized zone of pyroxenes, elongated in ilmenite, and irregular on the jagged surface of iron sulfide, but not found in Fe‐poor merrillite. Vesicles were found in the damaged zone of ilmenite and merrillite, but with different shapes. The observations were compared to Apollo samples and demonstrate no significant altitude‐dependent effects on the SW, which is important for decoding the reflectance spectra of the Moon.
The blood-brain barrier in aging and neurodegeneration
Authors: Knox Emily G. , Aburto Maria R. , Clarke Gerard , Cryan John F. , O’Driscoll Caitriona M.
Published: March 2022

The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange of compounds between the blood and the brain parenchyma. Moreover, the BBB prevents unwanted toxins and pathogens from entering the brain. This barrier, however, breaks down with age and further disruption is a hallmark of many age-related disorders. Several drugs have been explored, thus far, to protect or restore BBB function. With the recent connection between the BBB and gut microbiota, microbial-derived metabolites have been explored for their capabilities to protect and restore BBB physiology. This review, will focus on the vital components that make up the BBB, dissect levels of disruption of the barrier, and discuss current drugs and therapeutics that maintain barrier integrity and the recent discoveries of effects microbial-derived metabolites have on BBB physiology.
Developing symptom clusters: linking inflammatory biomarkers to depressive symptom profiles
Authors: Franklyn Sabina I. , Stewart Jayme , Beaurepaire Cecile , Thaw Emily , McQuaid Robyn J.
Published: March 2022

Considering the burden of depression and the lack of efficacy of available treatments, there is a need for biomarkers to predict tailored or personalized treatments. However, identifying reliable biomarkers for depression has been challenging, likely owing to the vast symptom heterogeneity and high rates of comorbidity that exists. Examining biomarkers that map onto dimensions of depression as well as shared symptoms/constructs that cut across disorders could be most effective for informing personalized treatment approaches. With a sample of 539 young adults, we conducted a principal component analysis (PCA) followed by hierarchical cluster analysis to develop transdiagnostic clusters of depression and anxiety symptoms. We collected blood to assess whether neuroendocrine (cortisol) and inflammatory profiles (C-reactive protein (CRP), Interleukin (IL)-6, and tumor necrosis factor (TNF) – α) could be used to differentiate symptom clusters. Six distinct clusters were identified that differed significantly on symptom dimensions including somatic anxiety, general anxiety, anhedonia, and neurovegetative depression. Moreover, the neurovegetative depression cluster displayed significantly elevated CRP levels compared to other clusters. In fact, inflammation was not strongly associated with overall depression scores or severity, but rather related to specific features of depression marked by eating, appetite, and tiredness. This study emphasizes the importance of characterizing the biological underpinnings of symptom dimensions and subtypes to better understand the etiology of complex mental health disorders such as depression.
DNA methylation signatures in human neonatal blood following maternal antenatal corticosteroid treatment
Authors: Kim Bona , Sasaki Aya , Murphy Kellie , Matthews Stephen G.
Published: March 2022

Antenatal corticosteroids (ACS) are used to treat women at risk of preterm birth to improve neonatal survival. Though affected children may be at long-term risk of neurobehavioural disorders, the driving mechanisms remain unknown. Animal studies have shown that ACS exposure can lead to overlapping changes in DNA methylation between the blood and the brain, identifying gene pathways for neurodevelopment, which highlights the potential to examine peripheral blood as a surrogate for inaccessible human brain tissue. We hypothesized that differential methylation will be identified in blood of term-born neonates following ACS. Mother-infant dyads that received ACS were retrospectively identified through the Ontario Birth Study at Sinai Health Complex and matched to untreated controls for maternal age, BMI, parity and foetal sex (n = 14/group). Genome-wide methylation differences were examined at single-nucleotide resolution in DNA extracted from dried bloodspot cards using reduced representative bisulfite sequencing approaches. 505 differentially methylated CpG sites (DMCs) were identified, wherein 231 were hypermethylated and 274 were hypomethylated. These sites were annotated to 219 genes, of which USP48, SH3PXD2A, NTM, CAMK2N2, MAP6D1 were five of the top ten genes with known neurological function. Collectively, the set of hypermethylated genes were enriched for pathways of transcription regulation, while pathways of proteasome activity were enriched among the set of hypomethylated genes. This study is the first to identify DNA methylation changes in human neonatal blood following ACS. Understanding the epigenetic changes that occur in response to ACS will support future investigations to delineate the effects of prenatal glucocorticoid exposure on human development.
Cell cycle regulation: p53-p21-RB signaling
Authors: Engeland Kurt
Published: March 2022

The retinoblastoma protein RB and the transcription factor p53 are central tumor suppressors. They are often found inactivated in various tumor types. Both proteins play central roles in regulating the cell division cycle. RB forms complexes with the E2F family of transcription factors and downregulates numerous genes. Among the RB-E2F target genes, a large number code for key cell cycle regulators. Their transcriptional repression by the RB-E2F complex is released through phosphorylation of RB, leading to expression of the cell cycle regulators. The release from repression can be prevented by the cyclin-dependent kinase inhibitor p21/CDKN1A. The CDKN1A gene is transcriptionally activated by p53. Taken together, these elements constitute the p53-p21-RB signaling pathway. Following activation of p53, for example by viral infection or induction of DNA damage, p21 expression is upregulated. High levels of p21 then result in RB-E2F complex formation and downregulation of a large number of cell cycle genes. Thus, p53-dependent transcriptional repression is indirect. The reduced expression of the many regulators leads to cell cycle arrest. Examination of the p53-p21-RB targets and genes controlled by the related p53-p21-DREAM signaling pathway reveals that there is a large overlap of the two groups. Mechanistically this can be explained by replacing RB-E2F complexes with the DREAM transcriptional repressor complex at E2F sites in target promoters. In contrast to RB-E2F, DREAM can downregulate genes also through CHR transcription factor binding sites. This results in a distinct gene set controlled by p53-p21-DREAM signaling independent of RB-E2F. Furthermore, RB has non-canonical functions without binding to E2F and DNA. Such a role of RB supporting DREAM formation may be exerted by the RB-SKP2-p27-cyclin A/E-CDK2-p130-DREAM link. In the current synopsis, the mechanism of regulation by p53-p21-RB signaling is assessed and the overlap with p53-p21-DREAM signaling is examined.
Hyper-CEST NMR of metal organic polyhedral cages reveals hidden diastereomers with diverse guest exchange kinetics
Authors: Jayapaul Jabadurai , Komulainen Sanna , Zhivonitko Vladimir V. , Mareš Jiří , Giri Chandan , Rissanen Kari , Lantto Perttu , Telkki Ville-Veikko , Schröder Leif
Published: March 2022

Guest capture and release are important properties of self-assembling nanostructures. Over time, a significant fraction of guests might engage in short-lived states with different symmetry and stereoselectivity and transit frequently between multiple environments, thereby escaping common spectroscopy techniques. Here, we investigate the cavity of an iron-based metal organic polyhedron (Fe-MOP) using spin-hyperpolarized 129Xe Chemical Exchange Saturation Transfer (hyper-CEST) NMR. We report strong signals unknown from previous studies that persist under different perturbations. On-the-fly delivery of hyperpolarized gas yields CEST signatures that reflect different Xe exchange kinetics from multiple environments. Dilute pools with ~ 104-fold lower spin numbers than reported for directly detected hyperpolarized nuclei are readily detected due to efficient guest turnover. The system is further probed by instantaneous and medium timescale perturbations. Computational modeling indicates that these signals originate likely from Xe bound to three Fe-MOP diastereomers (T, C3, S4). The symmetry thus induces steric effects with aperture size changes that tunes selective spin manipulation as it is employed in CEST MRI agents and, potentially, impacts other processes occurring on the millisecond time scale.
Magnetic refrigeration material operating at a full temperature range required for hydrogen liquefaction
Authors: Tang Xin , Sepehri-Amin H. , Terada N. , Martin-Cid A. , Kurniawan I. , Kobayashi S. , Kotani Y. , Takeya H. , Lai J. , Matsushita Y. , Ohkubo T. , Miura Y. , Nakamura T. , Hono K.
Published: March 2022

Magnetic refrigeration (MR) is a key technique for hydrogen liquefaction. Although the MR has ideally higher performance than the conventional gas compression technique around the hydrogen liquefaction temperature, the lack of MR materials with high magnetic entropy change in a wide temperature range required for the hydrogen liquefaction is a bottle-neck for practical applications of MR cooling systems. Here, we show a series of materials with a giant magnetocaloric effect (MCE) in magnetic entropy change (-∆Sm > 0.2 J cm−3K−1) in the Er(Ho)Co2-based compounds, suitable for operation in the full temperature range required for hydrogen liquefaction (20-77 K). We also demonstrate that the giant MCE becomes reversible, enabling sustainable use of the MR materials, by eliminating the magneto-structural phase transition that leads to deterioration of the MCE. This discovery can lead to the application of Er(Ho)Co2-based alloys for the hydrogen liquefaction using MR cooling technology for the future green fuel society.
Human seasonal influenza under COVID-19 and the potential consequences of influenza lineage elimination
Authors: Dhanasekaran Vijaykrishna , Sullivan Sheena , Edwards Kimberly M. , Xie Ruopeng , Khvorov Arseniy , Valkenburg Sophie A. , Cowling Benjamin J. , Barr Ian G.
Published: March 2022

Annual epidemics of seasonal influenza cause hundreds of thousands of deaths, high levels of morbidity, and substantial economic loss. Yet, global influenza circulation has been heavily suppressed by public health measures and travel restrictions since the onset of the COVID-19 pandemic. Notably, the influenza B/Yamagata lineage has not been conclusively detected since April 2020, and A(H3N2), A(H1N1), and B/Victoria viruses have since circulated with considerably less genetic diversity. Travel restrictions have largely confined regional outbreaks of A(H3N2) to South and Southeast Asia, B/Victoria to China, and A(H1N1) to West Africa. Seasonal influenza transmission lineages continue to perish globally, except in these select hotspots, which will likely seed future epidemics. Waning population immunity and sporadic case detection will further challenge influenza vaccine strain selection and epidemic control. We offer a perspective on the potential short- and long-term evolutionary dynamics of seasonal influenza and discuss potential consequences and mitigation strategies as global travel gradually returns to pre-pandemic levels.
Individual experience as a key to success for the cuckoo catfish brood parasitism
Authors: Zimmermann Holger , Blažek Radim , Polačik Matej , Reichard Martin
Published: March 2022

Brood parasites are involved in coevolutionary arms races with their hosts, whereby adaptations of one partner elicit the rapid evolution of counter-adaptations in the other partner. Hosts can also mitigate fitness costs of brood parasitism by learning from individual or social experience. In brood parasites, however, the role of learning can be obscured by their stealthy behaviour. Cuckoo catfish (Synodontis multipunctatus) parasitise clutches of mouthbrooding cichlids in Lake Tanganyika and are the only non-avian obligate brood parasites among vertebrates. We experimentally demonstrate that cuckoo catfish greatly enhance their efficiency in parasitising their hosts as they learn to overcome host defences. With increasing experience, cuckoo catfish increased their parasitism success by greater efficiency through improved timing and coordination of intrusions of host spawnings. Hence, within the coevolutionary arms races, brood parasites learn to overcome host defences during their lifetime.
Integration of resonant band with asymmetry in ferroelectric tunnel junctions
Authors: Su Jing , Li Jing , Zheng Xingwen , Xie Shijie , Liu Xiaohui
Published: March 2022

We propose that the asymmetry-induced tunneling electroresistance (TER) effect in a ferroelectric tunnel junction (FTJ) could be improved by integrating a polarization-controlled resonant band. Using first-principles calculations and a quantum-mechanical tunneling model, we studied an asymmetric FTJ SrRuO3/BaTiO3/SrTiO3/SrRuO3. The resonant band is integrated into this FTJ by two atomic layers of BaSnO3embedded in the barrier. In the elaborated FTJ SrRuO3/BaTiO3/BaSnO3/SrTiO3/SrRuO3, both resonant band and asymmetry work together. For one polarization direction, the BaSnO3and SrTiO3dielectric layers work together as barriers to provide considerable efficient barrier height for direct tunneling and lead to large tunneling resistance. For the opposite polarization, the BaSnO3layer serves as a quantum well to induce resonant tunneling across the barrier and considerably reduces the tunneling resistance of the ON state. The integration of resonant band with asymmetry may provide a more efficient and applicable way to further improve the functionalities of FTJs.
Estimating medical risk in human spaceflight
Authors: Antonsen Erik L. , Myers Jerry G. , Boley Lynn , Arellano John , Kerstman Eric , Kadwa Binaifer , Buckland Daniel M. , Van Baalen Mary
Published: March 2022

NASA and commercial spaceflight companies will soon be retuning humans to the Moon and then eventually sending them on to Mars. These distant planetary destinations will pose new risks—in particular for the health of the astronaut crews. The bulk of the evidence characterizing human health and performance in spaceflight has come from missions in Low Earth Orbit. As missions last longer and travel farther from Earth, medical risk is expected to contribute an increasing proportion of total mission risk. To date, there have been no reliable estimates of how much. The Integrated Medical Model (IMM) is a Probabilistic Risk Assessment (PRA) Monte-Carlo simulation tool developed by NASA for medical risk assessment. This paper uses the IMM to provide an evidence-based, quantified medical risk estimate comparison across different spaceflight mission durations. We discuss model limitations and unimplemented capabilities providing insight into the complexity of medical risk estimation for human spaceflight. The results enable prioritization of medical needs in the context of other mission risks. These findings provide a reasonable bounding estimate for medical risk in missions to the Moon and Mars and hold value for risk managers and mission planners in performing cost-benefit trades for mission capability and research investments.
A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves
Authors: Chen Joshua C. , Kan Peter , Yu Zhanghao , Alrashdan Fatima , Garcia Roberto , Singer Amanda , Lai C. S. Edwin , Avants Ben , Crosby Scott , Li Zhongxi , Wang Boshuo , Felicella Michelle M. , Robledo Ariadna , Peterchev Angel V. , Goetz Stefan M. , Hartgerink Jeffrey D. , Sheth Sunil A. , Yang Kaiyuan , Robinson Jacob T.
Published: March 2022

Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via a digitally programmable 1 mm × 0.8 mm system-on-a-chip. Implantation of the device directly on top of the sciatic nerve in rats and near a femoral artery in pigs (with a stimulation lead introduced into a blood vessel through a catheter) allowed for wireless stimulation of the animals’ sciatic and femoral nerves. Minimally invasive magnetoelectric implants may allow for the stimulation of nerves without the need for open surgery or the implantation of battery-powered pulse generators.
1H NMR based urinary metabolites profiling dataset of canine mammary tumors
Authors: Lee Songyeon , Seung Byung-Joon , Yang In Seok , Lee Jueun , Ha Taewoong , Park Hee-Myung , Cheong Jae-Ho , Kim Sangwoo , Sur Jung-Hyang , Hwang Geum-Sook , Nam Hojung
Published: March 2022

The identification of efficient and sensitive biomarkers for non-invasive tests is one of the major challenges in cancer diagnosis. To address this challenge, metabolomics is widely applied for identifying biomarkers that detect abnormal changes in cancer patients. Canine mammary tumors exhibit physiological characteristics identical to those in human breast cancer and serve as a useful animal model to conduct breast cancer research. Here, we aimed to provide a reliable large-scale metabolite dataset collected from dogs with mammary tumors, using proton nuclear magnetic resonance spectroscopy. We identified 55 metabolites in urine samples from 20 benign, 87 malignant, and 49 healthy control subjects. This dataset provides details of mammary tumor-specific metabolites in dogs and insights into cancer-specific metabolic alterations that share similar molecular characteristics.
Small brains predisposed Late Quaternary mammals to extinction
Authors: Dembitzer Jacob , Castiglione Silvia , Raia Pasquale , Meiri Shai
Published: March 2022

The Late Quaternary witnessed a dramatic wave of large mammal extinctions, that are usually attributed to either human hunting or climatic change. We hypothesized that the large mammals that survived the extinctions might have been endowed with larger brain sizes than their relatives, which could have conferred enhanced behavioral plasticity and the ability to cope with the rapidly changing Late Quaternary environmental conditions. We assembled data on brain sizes of 291 extant mammal species plus 50 more that went extinct during the Late Quaternary. Using logistic, and mixed effect models, and controlling for phylogeny and body mass, we found that large brains were associated with higher probability to survive the Late Quaternary extinctions, and that extant species have brains that are, on average, 53% larger when accounting for order as a random effect, and 83% when fitting a single regression line. Moreover, we found that models that used brain size in addition to body size predicted extinction status better than models that used only body size. We propose that possessing a large brain was an important, yet so far neglected characteristic of surviving megafauna species.
Newly discovered dimensional effects of electrodes on liquid crystal THz phase shifters enable novel switching between in-plane and out-of-plane
Authors: Oh-e Masahito , Zheng Deng-Yun
Published: March 2022

To unveil a novel switching mechanism in liquid crystal (LC)-based phase shifters for the THz range, we analyse how the dimensions of the electrode structures enable a new type of switching, namely, THz in-plane and THz out-of-plane (TIP–TOP) switching. Specifically, we determine how varying these electrode dimensions influences the LC in-plane states with the corresponding phase shifts by calculating these effects in virtual devices. Interestingly, we found that significant dimensional effects of the in-plane electrode structures statically and dynamically influence the phase shift and response time of LC switching. Analysing the electromagnetic fields in the TIP–TOP cell clearly reveals that these dimensional effects are due to changes in the electric field strengths caused by lateral bus-line electrodes that were originally assumed not to contribute to the switching. Further, we discover that the ultimate dimensional effect produces a novel type of LC switching, which results in hexadirectional switching between the initial, intrinsic in-plane, and out-of-plane reorientations of the LCs, suggesting a broader range of phase shifts while maintaining a rapid response.
NeuroSCORE is a genome-wide omics-based model that identifies candidate disease genes of the central nervous system
Authors: Davis Kyle W. , Bilancia Colleen G. , Martin Megan , Vanzo Rena , Rimmasch Megan , Hom Yolanda , Uddin Mohammed , Serrano Moises A.
Published: March 2022

To identify candidate disease genes of central nervous system (CNS) phenotypes, we created the Neurogenetic Systematic Correlation of Omics-Related Evidence (NeuroSCORE). We identified five genome-wide metrics highly associated with CNS phenotypes to score 19,601 protein-coding genes. Genes scored one point per metric (range: 0–5), identifying 8298 scored genes (scores ≥ 1) and 1601 “high scoring” genes (scores ≥ 3). Using logistic regression, we determined the odds ratio that genes with a NeuroSCORE from 1 to 5 would be associated with known CNS-related phenotypes compared to genes that scored zero. We tested NeuroSCORE using microarray copy number variants (CNVs) in case–control cohorts and aggregate mouse model data. High scoring genes are associated with CNS phenotypes (OR = 5.5, p < 2e-16), enriched in case CNVs, and mouse ortholog genes that cause behavioral and nervous system abnormalities. We identified 1058 high scoring genes with no disease association in OMIM. Transforming the logistic regression results indicates high scoring genes have an 84–92% chance of being associated with a CNS phenotype. Top scoring genes include GRIA1, MAP4K4, SF1, TNPO2, and ZSWIM8. Finally, we interrogated CNVs in the Clinical Genome Resource, finding the majority of clinically significant CNVs contain high scoring genes. These findings can direct future research and improve molecular diagnostics.
Combination of mean CT value and maximum CT value as a novel predictor of lepidic predominant lesions in small lung adenocarcinoma presenting as solid nodules
Authors: Koezuka Satoshi , Sano Atsushi , Azuma Yoko , Sakai Takashi , Matsumoto Keiko , Shiraga Nobuyuki , Mikami Tetuo , Tochigi Naobumi , Murakami Yoshitaka , Iyoda Akira
Published: March 2022

Lung adenocarcinomas presenting as solid nodules are occasionally diagnosed as lepidic predominant lesions. The aim of this study was to clarify the histological structure and to identify factors predictive of lepidic predominant lesions. We retrospectively reviewed 38 patients that underwent lobectomy for small (≤ 2 cm) adenocarcinoma presenting as solid nodules. Resected tumor slides were reviewed and histological components were evaluated. Clinical and radiological data were analyzed to identify factors predictive of lepidic predominant lesions. Of 38 solid nodules, 9 (23.7%) nodules were lepidic predominant lesions. Five-year disease-free survival (DFS) rates were 100% for lepidic predominant lesions (n = 9) and 74.6% for non-lepidic predominant lesions (n = 29). Mean CT values (p = 0.039) and maximum CT values (p = 0.015) were significantly lower in lepidic predominant lesions compared with non-lepidic predominant lesions. For the prediction of lepidic predominant lesions, the sensitivity and specificity of mean CT value (cutoff, − 150 HU) were 77.8% and 82.8%, respectively, and those of maximum CT value (cutoff, 320 HU) were 77.8% and 72.4%, respectively. A combination of mean and maximum CT values (cutoffs of − 150 HU and 380 HU for mean CT value and maximum CT value, respectively) more accurately predicted lepidic predominant lesions, with a sensitivity and specificity of 77.8% and 86.2%, respectively. The prognosis of lepidic predominant lesions was excellent, even for solid nodules. The combined use of mean and maximum CT values was useful for predicting lepidic predominant lesions, and may help predict prognosis.
Predicting non-response to multimodal day clinic treatment in severely impaired depressed patients: a machine learning approach
Authors: Vetter Johannes Simon , Schultebraucks Katharina , Galatzer-Levy Isaac , Boeker Heinz , Brühl Annette , Seifritz Erich , Kleim Birgit
Published: March 2022

A considerable number of depressed patients do not respond to treatment. Accurate prediction of non-response to routine clinical care may help in treatment planning and improve results. A longitudinal sample of N = 239 depressed patients was assessed at admission to multi-modal day clinic treatment, after six weeks, and at discharge. First, patient’s treatment response was modelled by identifying longitudinal trajectories using the Hamilton Depression Rating Scale (HDRS-17). Then, individual items of the HDRS-17 at admission as well as individual patient characteristics were entered as predictors of response/non-response trajectories into the binary classification model (eXtremeGradient Boosting; XGBoost). The model was evaluated on a hold-out set and explained in human-interpretable form by SHapley Additive explanation (SHAP) values. The prediction model yielded a multi-class AUC = 0.80 in the hold-out set. The predictive power for the binary classification yielded an AUC = 0.83 (sensitivity = .80, specificity = .77). Most relevant predictors for non-response were insomnia symptoms, younger age, anxiety symptoms, depressed mood, being unemployed, suicidal ideation and somatic symptoms of depressive disorder. Non-responders to routine treatment for depression can be identified and screened for potential next-generation treatments. Such predictors may help personalize treatment and improve treatment response.
Effect of non-repetitive linker on in vitro and in vivo properties of an anti-VEGF scFv
Authors: Arslan Merve , Karadag Murat , Onal Ebru , Gelinci Emine , Cakan-Akdogan Gulcin , Kalyoncu Sibel
Published: March 2022

Single chain antibody fragments (scFvs) are favored in diagnostic and therapeutic fields thanks to their small size and the availability of various engineering approaches. Linker between variable heavy (VH) and light (VL) chains of scFv covalently links these domains and it can affect scFv’s bio-physical/chemical properties and in vivo activity. Thus, scFv linker design is important for a successful scFv construction, and flexible linkers are preferred for a proper pairing of VH–VL. The flexibility of the linker is determined by length and sequence content and glycine-serine (GS) linkers are commonly preferred for scFvs based on their highly flexible profiles. Despite the advantage of this provided flexibility, GS linkers carry repeated sequences which can cause problems for PCR-based engineering approaches and immunogenicity. Here, two different linkers, a repetitive GS linker and an alternative non-repetitive linker with similar flexibility but lower immunogenicity are employed to generate anti-Vascular Endothelial Growth Factor scFvs derived from bevacizumab. Our findings highlight a better in vitro profile of the non-repetitive linker such as a higher monomer ratio, higher thermal stability while there was no significant difference in in vivo efficacy in a zebrafish embryonic angiogenesis model. This is the first study to compare in vivo efficacy of scFvs with different linkers in a zebrafish model.
Vitiligo-specific soluble biomarkers as early indicators of response to immune checkpoint inhibitors in metastatic melanoma patients
Authors: Carbone Maria Luigia , Madonna Gabriele , Capone Alessia , Bove Marianna , Mastroeni Simona , Levati Lauretta , Capone Mariaelena , Ascierto Paolo Antonio , De Galitiis Federica , D’Atri Stefania , Fortes Cristina , Volpe Elisabetta , Failla Cristina Maria
Published: March 2022

Immunotherapy with checkpoint inhibitors (CPIs) strongly improved the outcome of metastatic melanoma patients. However, not all the patients respond to treatment and identification of prognostic biomarkers able to select responding patients is currently of outmost importance. Considering that development of vitiligo-like depigmentation in melanoma patients represents both an adverse event of CPIs and a favorable prognostic factor, we analyzed soluble biomarkers of vitiligo to validate them as early indicators of response to CPIs. Fifty-seven metastatic melanoma patients receiving CPIs were enrolled and divided according to the best overall response to treatment. Patient sera were evaluated at pre-treatment and after 1 and 3 months of therapy. We found that basal CD25 serum levels were higher in stable and responding patients and remained higher during the first 3 months of CPI therapy compared to non-responders. CXCL9 was absent in non-responding patients before therapy beginning. Moreover, an increase of CXCL9 levels was observed at 1 and 3 months of therapy for all patients, although higher CXCL9 amounts were present in stable and responding compared to non-responding patients. Variations in circulating immune cell subsets was also analyzed, revealing a reduced number of regulatory T lymphocytes in responding patients. Altogether, our data indicate that a pre-existing and maintained activation of the immune system could be an indication of response to CPI treatment in melanoma patients.
Multi-class sentiment analysis of urdu text using multilingual BERT
Authors: Khan Lal , Amjad Ammar , Ashraf Noman , Chang Hsien-Tsung
Published: March 2022

Sentiment analysis (SA) is an important task because of its vital role in analyzing people’s opinions. However, existing research is solely based on the English language with limited work on low-resource languages. This study introduced a new multi-class Urdu dataset based on user reviews for sentiment analysis. This dataset is gathered from various domains such as food and beverages, movies and plays, software and apps, politics, and sports. Our proposed dataset contains 9312 reviews manually annotated by human experts into three classes: positive, negative and neutral. The main goal of this research study is to create a manually annotated dataset for Urdu sentiment analysis and to set baseline results using rule-based, machine learning (SVM, NB, Adabbost, MLP, LR and RF) and deep learning (CNN-1D, LSTM, Bi-LSTM, GRU and Bi-GRU) techniques. Additionally, we fine-tuned Multilingual BERT(mBERT) for Urdu sentiment analysis. We used four text representations: wordn-grams, charn-grams,pre-trained fastText and BERT word embeddings to train our classifiers. We trained these models on two different datasets for evaluation purposes. Finding shows that the proposed mBERT model with BERT pre-trained word embeddings outperformed deep learning, machine learning and rule-based classifiers and achieved an F1 score of 81.49%.
Smoking cessation behaviors and reasons for use of electronic cigarettes and heated tobacco products among Romanian adults
Authors: Hussain Sumaira , Sreeramareddy Chandrashekhar T.
Published: March 2022

We report cessation behaviors, reasons for use of electronic cigarettes (EC) and heated tobacco products (HTP) and association of their use with quit attempts and smoking intensity using Romania Global Adult Tobacco Survey 2018. Weighted estimates of EC and HTP by cigarette smoking (CS) status were assessed. Quit attempts, intention to quit, reasons for lack of intention to quit among current CS, and reasons for current use of EC and HTP were estimated. The association of ‘ever use’ of EC and HTP with cigarette smoking intensity and quit attempts was explored using binary logistic regression. Of the total 4571 surveyed, 1243 (27.3%) were current CS, 300 (24.4%) made quit attempts in the past 12 months. Only 38 (12.5%) and 26 (8.6%) had used EC and HTP as an aid to quit. Among current CS, 512 (41.2%) had no intention to quit. Reasons for this were, ‘enjoy smoking’ (86.1%), ‘reduce stress’ (65.9%), and ‘staying alert’ (46.3%). Awareness and use of EC and HTP were significantly higher among current CS. ‘Dual use’ of EC and HTP with CS was manifolds higher than stand-alone use. Reasons for current use of EC and HTP were ‘enjoyment’, and ‘use in places where smoking was prohibited’.
Implementation of an interactive virtual microscope laboratory system in teaching oral histopathology
Authors: Qing Jia , Cheng Gu , Ni Xiao-Qi , Yang Yi , Zhang Wei , Li Zhi
Published: March 2022

Laboratory course acts as a key component of histopathology education. Recent trends of incorporating visual and interactive technology in active and inquiry-based learning pedagogical methods have led to significant improvement of histopathology laboratory courses. The present work aimed to describe interactive virtual microscope laboratory system (IVMLS) as a virtual platform for teaching histopathology in order to improve the quality and efficiency of teaching. The system is based on interactive technology and consists of interactive software, slide-reading software, teaching resources and integrated auxiliary equipment. It allows real-time interaction between teachers and students and provides students with a wealth of learning and review materials. In order to evaluate the effectiveness of the system, we conducted a comparative study with the use of light microscope (LM) as a method. Specifically, we compared the results of six assignments and one laboratory final exam between IVMLS group and LM group to analyse the impact of IVMLS on students' academic performance. A questionnaire survey was also conducted to obtain students' attitudes and views on this system. There was no overall difference in assignment performance between IVMLS group and LM group. But laboratory final test grades increased from a mean of 62% (43.8–80.0, 95% CI) before to 83% (71.0–94.2, 95% CI) after implement IVMLS, suggesting highly significant (p < 0.001) improvement on students' histopathology laboratory performance. Feedback of the questionnaire was positive, indicating that students were satisfied with the system, which they believed improved student communication and teacher-student interaction, increased learning resources, increased their focus on learning, and facilitated their independent thinking process. This study proves that IVMLS is an efficient and feasible teaching technology and improves students' academic performance.
Machine learning to predict effective reaction rates in 3D porous media from pore structural features
Authors: Liu Min , Kwon Beomjin , Kang Peter K.
Published: March 2022

Large discrepancies between well-mixed reaction rates and effective reactions rates estimated under fluid flow conditions have been a major issue for predicting reactive transport in porous media systems. In this study, we introduce a framework that accurately predicts effective reaction rates directly from pore structural features by combining 3D pore-scale numerical simulations with machine learning (ML). We first perform pore-scale reactive transport simulations with fluid–solid reactions in hundreds of porous media and calculate effective reaction rates from pore-scale concentration fields. We then train a Random Forests model with 11 pore structural features and effective reaction rates to quantify the importance of structural features in determining effective reaction rates. Based on the importance information, we train artificial neural networks with varying number of features and demonstrate that effective reaction rates can be accurately predicted with only three pore structural features, which are specific surface, pore sphericity, and coordination number. Finally, global sensitivity analyses using the ML model elucidates how the three structural features affect effective reaction rates. The proposed framework enables accurate predictions of effective reaction rates directly from a few measurable pore structural features, and the framework is readily applicable to a wide range of applications involving porous media flows.
Dynamic analysis of QTLs on plant height with single segment substitution lines in rice
Authors: Fu Yu , Zhao Hongyuan , Huang Jiongkai , Zhu Haitao , Luan Xin , Bu Suhong , Liu Zupei , Wang Xiaoling , Peng Zhiqin , Meng Lijun , Liu Guifu , Zhang Guiquan , Wang Shaokui
Published: March 2022

Dynamic regulation of QTLs remains mysterious. Single segment substitution lines (SSSLs) and conditional QTL mapping and functional QTL mappings are ideal materials and methods to explore dynamics of QTLs for complex traits. This paper analyzed the dynamics of QTLs on plant height with SSSLs in rice. Five SSSLs were verified with plant height QTLs first. All five QTLs had significant positive effects at one or more developmental stages except QTL1. They interacted each other, with negative effects before 49 d after transplanting and positive effects since then. The five QTLs selectively expressed in specific periods, mainly in the periods from 35 to 42 d and from 49 to 56 d after transplanting. Expressions of epistasis were dispersedly in various periods, negative effects appearing mainly before 35 d. The five QTLs brought the inflexion point ahead of schedule, accelerated growth and degradation, and changed the peak plant height, while their interactions had the opposite effects. The information will be helpful to understand the genetic mechanism for developmental traits.
Temporal patterns of chronic disease incidence after breast cancer: a nationwide population-based cohort study
Authors: Kang Danbee , Kang Minwoong , Hong Yun Soo , Park Jihwan , Lee Jin , Seo Hwa Jeong , Kim Dong Wook , Ahn Jin Seok , Park Yeon Hee , Lee Se Kyung , Shin Dong Wook , Guallar Eliseo , Cho Juhee
Published: March 2022

We conducted a retrospective cohort study to evaluate the temporal pattern of incidence of chronic conditions after developing breast cancer using a population-based national registry. We selected 84,969 women with newly diagnosed breast cancer between 2002 and 2016 and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). The main study exposure was incident breast cancer, considered as a time-varying exposure. The outcomes were incident cases of leukemia, endometrial cancer, myeloma, cardiomyopathy, osteoporosis, end stage renal disease (ESRD), pulmonary fibrosis, hypothyroidism, type 2 diabetes, hypertension and hyperlipidemia. The development of breast cancer was associated with a significantly increased risk of all outcomes analyzed except for ESRD and hypertension. The fully-adjusted risks of leukemia (HR 3.09; 95% CI 2.11–4.51), cardiomyopathy (HR 2.65; 95% CI 1.90–3.68), endometrial cancer (HR 3.53; 95% CI 2.76–4.53), hypothyroidism (HR 1.29; 95% CI 1.19–1.40), pulmonary fibrosis (HR 1.84; 95% CI 1.12–3.02), and hyperlipidemia (HR 1.24; 95% CI 1.20–1.28) remained significantly elevated after more than 5 years since diagnosis. Optimal care for breast cancer survivors requires close collaboration between oncologists and allied health care professionals to identify and manage the long-term morbidity and mortality associated with these chronic conditions.
Disease progression patterns and molecular resistance mechanisms to crizotinib of lung adenocarcinoma harboring ROS1 rearrangements
Authors: Zhang Yongchang , Huang Zhe , Zeng Liang , Zhang Xiangyu , Li Yizhi , Xu Qinqin , Yang Haiyan , Lizaso Analyn , Xu Chunwei , Liu Jun , Wang Wenxian , Song Zhengbo , Ou Sai-Hong Ignatius , Yang Nong
Published: March 2022

This retrospective study investigated the association between the pattern of disease progression and molecular mechanism of acquired resistance in a large cohort of 49 patients with ROS1-rearranged advanced non-small-cell lung cancer treated with first-line crizotinib. We found that treatment-emergent ROS1 point mutations were the major molecular mechanism of crizotinib resistance, particularly for patients who developed extracranial-only disease progression. Our findings highlight the importance of rebiopsy and gene testing for subsequent-line therapeutic management.
Insight into the dual action mechanism of 3V-PPh3 polymers as carriers and ligands in the Rh/3V-PPh3 heterogeneous catalytic hydroformylation of ethylene to propionaldehyde
Authors: Ma Jing , Zhu Mingxuan , Wang Yutong , Liu Meizhe , Wang Baohe
Published: March 2022

Vinyl-PPh3 ligand polymers supported single Rh sites catalyst solved the problem of Rh loss of precious metal in the synthesis of propionaldehyde.
Screening of pesticide distributions in foods of animal origin: a matrix-based approach for biotransfer factor modeling of grazing mammals
Authors: Li Zijian , Xiong Jie , Fantke Peter
Published: March 2022

A matrix-based approach implemented in the PBK model helps perform high-throughput simulation of residue levels in foods of animal origin.
Silicon reduces the uptake of cadmium in hydroponically grown rice seedlings: why nanoscale silica is more effective than silicate
Authors: Cui Jianghu , Jin Qian , Li Fangbai , Chen Lei
Published: March 2022

Nanoscale silica more effectively reduces the uptake and transport of cadmium than silicate in hydroponically grown rice seedlings.
l-Methionine supplementation attenuates high-fat fructose diet-induced non-alcoholic steatohepatitis by modulating lipid metabolism, fibrosis, and inflammation in rats
Authors: Navik Umashanker , Sheth Vaibhav G. , Sharma Nisha , Tikoo Kulbhushan
Published: March 2022

Recently, the protective effects of a methionine-rich diet on hepatic oxidative stress and fibrosis have been suggested but not adequately studied.
Nanoreactor of sarcosine oxidase-embedded ZIFs activates fluorescent response for diagnosis of prostate cancer
Authors: Hu Qianqian , Chen Guoning , Wang Lu , Cui Xia , Chang Chun , Fu Qiang
Published: March 2022

A fluorometric method was developed to detect sarcosine based on SOX@ZIF-8, which possessed great linearity, specificity, and easy operation.
Catalytic activity and stability of a Cr modified Co–Fe LDO catalyst in the simultaneous catalytic reduction of NOx and oxidation of o-DCB
Authors: Xing Yi , Zhang Hui , Su Wei , Wang Jiaqing , Zhang Wenbo , Wang Yan , Ma Mengying , Ma Zhiliang
Published: March 2022

In this paper, a Co–Fe LDO catalyst was prepared by combining K2Cr2O7 and Cr(NO3)3 to modify the LDH precursor.
Organic dyes supported on silicon-based materials: synthesis and applications as photocatalysts
Authors: Mora-Rodríguez Salma E. , Camacho-Ramírez Abygail , Cervantes-González Javier , Vázquez Miguel A. , Cervantes-Jauregui Jorge A. , Feliciano Alberto , Guerra-Contreras Antonio , Lagunas-Rivera Selene
Published: March 2022

The most important advance in photocatalysis in the last decade has been the synthesis and application of organic compounds to promote this process.
Comparative study of the elimination of copper, cadmium, and methylene blue from water by adsorption on the citrusSinensispeel and its activated carbon
Authors: El Malti Wassim , Hijazi Akram , Khalil Zahraa Abou , Yaghi Zahraa , Medlej Mohamad Kazem , Reda Mohamad
Published: March 2022

The accumulation of heavy metals and dyes in wastewater is a persistent environmental threat with serious hazards consequences affecting all living organisms. CitrusSinensispeel and its activated carbon particles effectively remove Cu(ii), Cd(ii), and MB from water.
Understanding the thermal stability of apalutamide crystalline solvates through crystal structure analyses and computational studies
Authors: Prashanth Jupally , Sivalakshmi Devi A. , Surov Artem O. , Voronin Alexander P. , Churakov Andrei V. , Perlovich German L. , Balasubramanian Sridhar
Published: March 2022

The conformational flexibility of APA molecules leads to different crystal packing. The stability of the solvent molecules in the crystal structures was established through their strong intermolecular interactions with the host molecule.
Doping effects on the antibonding states and carriers of two-dimensional PC6
Authors: Zhong Mi , Zeng Wei , Qin Han , Zhu Sheng-Hai , Li Xing-Han , Liu Fu-Sheng , Tang Bin , Liu Qi-Jun
Published: March 2022

The absence of a bandgap in pristine graphene severely restricts its application, and there is high demand for other novel two-dimensional (2D) materials.
Photocatalysis by graphitic carbon nitride modified with 0D, 1D, and 2D carbon-based nanomaterials
Authors: Wang Bo-Kai , Wang David K. , Hou Wen-Che
Published: March 2022

The structure–reactivity relationship of g-C3N4embedded with 0–2D carbon-based nanomaterials towards photocatalysis of emerging contaminants is presented.
Alternating aeration strategy to reduce aeration energy demand for aerobic granular sludge and analysis of microbial community dynamics
Authors: Wang Biao , Liu Shaogen , Yao Xin , Liu Yang , Qi Gongqi
Published: March 2022

A novel energy-saving aeration operational strategy is proposed to effectively reduce energy consumption and improve the denitrification capacity of aerobic granular sludge (AGS).