bluuebunny/crossref_metadata_2025 huggingface dataset:
Current understanding of adenoid cystic carcinoma in the gene expression and targeted therapy
Authors: Lin Quan-Quan , Sun Jin-Long , Wang Feng , Zhang Hai-Zhong , Zhou Ge , Xi Qing
Published: April 2023

Adenoid Cystic Carcinoma (ACC) has been considered as a "quiet" tumor. It is typically malignancy arising from exocrine glands with poor long-term prognosis due to high rate of recurrence and distant metastasis. It is characterized by perineural infiltration, distant metastasis, and positive incision edge. Surgery is the first line treatment for ACC, followed by cytotoxic chemotherapy and/or radiotherapy as adjuvant treatments to avoid recurrence. But recurrence or metastasis still occurs in more than 50% ACC. Recurrent and/or metastasis (R/M) ACC is usually incurable, and no systemic agent has been found effective. With the widespread use of whole exome sequencing (WES) and whole genome sequencing (WGS), its internal oncogenic mechanism is gradually revealed, which involving molecular mutations such as the MYB family gene translocation, Notch signal pathway, DNA damage repair (DDR) pathway and epigenetic molecular mutations. The review helps us to understand the linkage among the pathways and targeted genes in diagnosis and related treatment of ACC till now.
USDA Long-Term Meat Trade Projections: A Comprehensive Evaluation
Authors: Luke Jaime R. , Tonsor Glynn T.
Published: April 2023

The profitability of U.S. meat producers and the utility of U.S. meat consumers are impacted by the trade of meat. USDA publishes the most prominent publicly available meat trade projections. This study finds USDA projections typically underpredict meat export volumes and overpredict meat import volumes. USDA projections outperform naïve projections for beef and pork exports, but naïve projections at times outperform USDA projections for chicken exports and beef and pork imports, especially at shorter horizons. USDA projections exclude variety cuts, which comprise a sizeable share of beef and pork exports. There remains room for improvement in projecting U.S. meat trade.
Building leadership capacity among junior faculty: Evaluating multi-level outcomes of a leadership program
Authors: Fattah Layla , Bloom Lisa , Ventura Cara Della , Gabrilove Janice
Published: April 2023

Introduction:

Leadership is recognized as an essential competency across healthcare and science. The LEAD (Leadership Emerging in Academic Departments) program at the Icahn School of Medicine at Mount Sinai (ISMMS) is a structured 12-month blended learning program that catalyzes personal and professional leadership skills, behaviors, and capacity.

Methods:

Utilizing a post-program survey design, the Leadership Program Outcome Measure (LPOM) explored self-reported impact of the LEAD program on leadership knowledge and skills in relation to personal and organizational leadership constructs. Application of leadership skills to practice was tracked via completion of a leadership-focused capstone project.

Results:

Over 3 cohorts, 76 participants graduated and 50 completed the LPOM survey (68% response rate). Participants self-reported an increase in leadership skills, conveyed plans to use acquired skills in current and future leadership positions, and noted improved leadership skills across the personal and organizational domains. Comparatively less change was detected at the community level. Tracking of capstone projects found that 64% of participants were able to successfully implement their project in practice.

Conclusion:

LEAD was successful in promoting the development of personal and organizational leadership practices. The LPOM evaluation provided a valuable lens through which to assess the individual, interpersonal, and organizational impact of a multidimensional leadership training program.
Quantifying the scientific revolution
Authors: de Courson Benoît , Thouzeau Valentin , Baumard Nicolas
Published: April 2023

The Scientific Revolution represents a turning point in the history of humanity. Yet it remains ill-understood, partly because of a lack of quantification. Here, we leverage large datasets of individual biographies (N= 22,943) and present the first estimates of scientific production during the late medieval and early modern period (1300–1850). Our data reveal striking differences across countries, with England and the United Provinces being much more creative than other countries, suggesting that economic development has been key in generating the Scientific Revolution. In line with recent results in behavioural sciences, we show that scientific creativity and economic development are associated with other kinds of creative activities in philosophy, literature, music and the arts, as well as with inclusive institutions and ascetic religiosity, suggesting a common underlying mindset associated with long-term orientation and exploration. Finally, we investigate the interplay between economic development and cultural transmission (the so-called ‘Republic of Letters’) using partially observed Markov models imported from population biology. Surprisingly, the role of horizontal transmission (from one country to another) seems to have been marginal. Beyond the case of science, our results suggest that economic development is an important factor in the evolution of aspects of human culture.
A 2-year longitudinal evaluation of the impact of the COVID-19 pandemic on individuals with pre-existing anxiety disorders
Authors: McLoughlin A. , Mulholland K. , McMahon E. , Plunkett R. , Hennigan K. , McDonald C. , Hallahan B.
Published: April 2023

Objectives:

To examine if the COVID-19 pandemic is associated with a differential effect over a 2-year time period in relation to its psychological and social impact on patients with established anxiety disorders.

Methods:

Semi-structured interviews were conducted with 21 individuals attending the Galway-Roscommon Mental Health Services in Ireland with an ICD-10 diagnosis of an anxiety disorder. Interviews occurred at three time-points over a 2-year period to determine the impact of the COVID-19 pandemic and associated restrictions on anxiety and depressive symptoms, social and occupational functioning, and quality of life.

Results:

No statistical difference in symptomatology was noted between the three time-points in relation to anxiety symptoms as measured utilising psychometric rating scales (Beck Anxiety Inventory (BAI), Hamilton Anxiety Rating Scale (HARS) or Likert Scale measures). The greatest impact of COVID-19 at all time-points related to social functioning and quality of life. Significant variability was noted for individual participants. Qualitative analysis noted a tentative optimism for the future in the setting of vaccination and societal re-opening. Fear of re-emerging anxiety symptoms with the removal of societal restrictions was noted.

Conclusions:

No significant overall change in symptomatology or functioning over time was noted for individuals with pre-existing anxiety disorders, however variability was demonstrated, with some individuals describing ongoing anxiety, social isolation and concern for their future. A strong theme of hope for the future and less concern regarding the COVID-19 pandemic was evident; however tailored supports including the utilisation of tele-psychiatry is suggested, particularly for those experiencing increased anxiety with the removal of societal restrictions.
Adverse childhood experiences and reoccurrence of illness impact the gut microbiome, which affects suicidal behaviours and the phenome of major depression: towards enterotypic phenotypes
Authors: Maes Michael , Vasupanrajit Asara , Jirakran Ketsupar , Klomkliew Pavit , Chanchaem Prangwalai , Tunvirachaisakul Chavit , Plaimas Kitiporn , Suratanee Apichat , Payungporn Sunchai
Published: April 2023

The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maeset al., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviours (SB) and cognitive deficits; the effects of adverse childhood experiences (ACEs) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein cholesterol (HDLc). We determined isometric log-ratio abundances or prevalences of gut microbiome phyla, genera, and species by analysing stool samples from 37 healthy Thai controls and 32 MDD patients using 16S rDNA sequencing. Six microbiome taxa accounted for 36% of the variance in the depression phenome, namelyHungatellaandFusicatenibacter(positive associations) andButyricicoccus, Clostridium, Parabacteroides merdae, andDesulfovibrio piger(inverse association). This profile (labelled enterotype 1) indicates compositional dysbiosis, is strongly predicted by ACE and ROI, and is linked to SB. A second enterotype was developed that predicted a decrease in HDLc and an increase in the atherogenic index of plasma (Bifidobacterium, P. merdae, andRomboutsia were positively associated, whileProteobacteriaandClostridium sensu strictowere negatively associated). Together, enterotypes 1 and 2 explained 40.4% of the variance in the depression phenome, and enterotype 1 in conjunction with HDLc explained 39.9% of the variance in current SB. In conclusion, the microimmuneoxysome is a potential new drug target for the treatment of severe depression and SB and possibly for the prevention of future episodes.
Programmable polymers with shape memory for biomedical applications
Authors: Wang Kaojin , Man Limin , Zhang Meng , Jia Yong-Guang , Zhu X. X.
Published: April 2023

Shape memory polymers (SMPs) are a type of programmable materials capable of transforming their shapes in a pre-programmed way upon the application of an external stimulus. These materials have been tested for various potential applications particularly in the biomedical field for polymers with general and specific requirements. This review focuses on the recent advances in biomedical applications, including self-tightening sutures, pressure bandages, self-expansion stents, tissue engineering scaffolds, artificial muscles, drug delivery, and orthodontic archwires, after a brief description of the concepts, classifications, programming procedures, and material requirements of SMPs.
MODELING LONG-TERM HUMAN POPULATION DYNAMICS USING KERNEL DENSITY ANALYSIS OF 14C DATA IN THE ATACAMA DESERT (18º–21ºS)
Authors: Mendez-Quiros Pablo , Barceló Juan A , Santana-Sagredo Francisca , Uribe Mauricio
Published: April 2023

Food production is one of the most significant achievements in Andean history. The domestication of plants and animals presented an enormous challenge, relating to changing technologies, settlement patterns, and social organization. This paper aims to assess Atacama Desert population dynamics and their relationship to the domestication of plants and animals through chronological modeling using kernel density estimation on radiocarbon (14C) dates, assuming that a higher 14C probability density is related to more intense human occupation. The analysis is based on a 14C dataset comprising 1003 14C dates (between 11,000 and 150 BP) from 243 archaeological sites in the Arica and Tarapacá regions of northern Chile, collected from published data. We observed two population-dynamics inflection points for these regions. First, starting at ca. 3000 BP, constant population growth occurred, which was related to horticulture in the Arica region and to agriculture in the Tarapacá region. Second, between ca. 1000 and 400 BP, a general population rise occurred due to the consolidation of intensive agriculture in the lowlands and precordillera altitudinal belts in both regions and the integration of the coast and the altiplano into macro-regional population dynamics.
The effectiveness of spiritual care training on medical students’ self-reported competencies: A quasi-experimental study
Authors: Vitorino Luciano Magalhães , Machado Teixeira Pedro Henrique , Dominato Patricia Cabrelon , de Azevedo Maria Paula Cunha , Resende Mariana Maciel , Lucchetti Giancarlo
Published: April 2023

Objectives

To evaluate the effectiveness of spiritual care training on medical students’ self-reported competencies.

Methods

This is a quasi-experimental (controlled and non-randomized) study including 115 Brazilian medical students. Participants were enrolled into 2 groups: fourth-year students (n = 64) who received spiritual care training and sixth-year students (n = 51) who did not receive this training – control group (i.e., usual teaching). Participants answered a self-reported Spiritual Care Competence Scale. Comparisons between groups were performed and effect sizes were reported.

Results

Providing a spiritual care training resulted in significantly higher self-reported scores for the dimensions of “Assessment” (d = 0.99), “Improvement of care” (d = 0.69), “Counseling (d = 0.88),” “Referral” (d = 0.75), and “Total Spiritual Care” (d = 1.044) as compared to the control group. Likewise, 21 out of 27 items of the Spiritual Care Competence Scale were significantly higher for the intervention group, presenting effect sizes (d) ranging between 0.428 and 1.032.

Significance of results

Medical students receiving spiritual care training showed greater self-reported competencies as compared to those in the usual teaching. These results reinforce the importance of promoting spirituality teaching in medical schools.
Palaeo-climate and -topography of the continental orogen: Theoretical inversion with initial oxygen isotopes of ancient meteoric water
Authors: WEI Chun-Sheng , ZHAO Zi-Fu
Published: April 2023

Ancient environments have been mostly reconstructed with exogenous records, yet the potential constraints from endogenous archives were less emphasised. It has been well known that the outer- and inner-spheres of the planetary Earth are naturally linked and/or interplayed each other among geospheres. As stable isotopes of the meteoric water are globally dependent upon precipitating environments, rocks and/or minerals hydrothermally altered by the meteoric water can thus imprint environmental information of continental settings. These valuable clues, however, have been intuitively and/or qualitatively inferred up to now. On the basis of an innovative procedure recently proposed for dealing with thermodynamic re-equilibration of oxygen isotopes between constituent minerals and water from fossil hydrothermal systems, ancient meteoric waters are theoretically inverted from the early Cretaceous post-collisional granitoid and Triassic gneissic country rocks across the Dabie orogen in central-eastern China. The initial oxygen isotopes of ancient meteoric water (i.e., $\delta ^{18}O_W^i$ value hereafter) range from −11.01 ± 0.43 (one standard deviation, 1SD) to −7.61 ± 0.07‰ in this study, yet systematically and/or statistically deviating from modern local precipitation. These imply that either palaeoclimate could be colder than the present at least during the early Cretaceous or palaeoaltimetry has geographically varied across the Dabie orogen since the Triassic. Moreover, the lifetime of fossil hydrothermal systems is kinetically quantified to less than 1.2 million years (Myr) for the concurrent lowering of oxygen isotopes of hydrothermally altered rock-forming minerals through the surface-reaction oxygen exchange with ancient meteoric waters herein. Our results thus suggest that palaeoenvironments of the continental orogen can be scientifically and methodologically unearthed from endogenous archives and theoretical inversion of $\delta ^{18}O_W^i$ values can be quantitatively applied beyond the Dabie orogen.
Environmental drivers of human migration in Sub-Saharan Africa
Authors: Wolde Sinafekesh Girma , D'Odorico Paolo , Rulli Maria Cristina
Published: April 2023

Non-technical summary

Environmental threats to shelter, livelihoods, and food security are often considered push factors for intra-African human migration. Research in this field is often fragmented into a myriad of case studies on specific subregions or events, thus preventing a more comprehensive understanding of the phenomenon. This paper examines environmental drivers reported in the literature as push factors for human displacement across 32 sub-Saharan African countries between 1990 and 2021. Extensive consultation of past studies and reports with analytical methods shows that environmental migration is complex and influenced by multiple direct and indirect factors. Non-environmental drivers compound the effects of environmental change.

Technical summary

Intra-African environmental migration is a bleak reality. Warming trends, aridification, and the intensification of extreme climate events, combined with underlying non-environmental drivers, may set millions of people on the move. Despite previous studies and meta-analyses on environmental migration within sub-Saharan Africa (SSA), conclusive empirical evidence of the relationship between environmental change and migration is still missing. Here we draw on 87 case studies published in the scholarly literature (from fields ranging from the environmental sciences to development economics and migration research) or documented by research databases, reports, and international disaster datasets to develop a meta-analysis investigating the relationship between environmental changes and migration across SSA. A combination of quantitative, Qualitative Comparative Analyses (QCA), and statistical correlation methods are used to analyze the metadata and investigate the complex web of environmental drivers of environmental migration in SSA while highlighting subregional differences in the predominant environmental forcing. We develop a new conceptual framework for investigating the cascading flow of interdependences among environmental change drivers of human displacement while reconstructing the main migration patterns across SSA. We also present new insights into the way non-environmental factors are exposing communities in SSA to high vulnerability and reduced resilience to environmental change.

Social media summary

Human displacement in sub-Saharan Africa is often associated with the effects of climate change and environmental degradation.
Social Vulnerability and Groundwater Vulnerability to Contamination From Unconventional Hydrocarbon Extraction in the Appalachian Basin
Authors: Soriano Mario A. , Warren Joshua L. , Clark Cassandra J. , Johnson Nicholaus P. , Siegel Helen G. , Deziel Nicole C. , Saiers James E.
Published: April 2023

Unconventional oil and gas (UOG) development, made possible by horizontal drilling and high‐volume hydraulic fracturing, has been fraught with controversy since the industry's rapid expansion in the early 2000's. Concerns about environmental contamination and public health risks persist in many rural communities that depend on groundwater resources for drinking and other daily needs. Spatial disparities in UOG risks can pose distributive environmental injustice if such risks are disproportionately borne by marginalized communities. In this paper, we analyzed groundwater vulnerability to contamination from UOG as a physically based measure of risk in conjunction with census tract level sociodemographic characteristics describing social vulnerability in the northern Appalachian Basin. We found significant associations between elevated groundwater vulnerability and lower population density, consistent with UOG development occurring in less densely populated rural areas. We also found associations between elevated groundwater vulnerability and lower income, higher proportions of elderly populations, and higher proportion of mobile homes, suggesting a disproportionate risk burden on these socially vulnerable groups. We did not find a statistically significant association between elevated groundwater vulnerability and populations of racial/ethnic minorities in our study region. Household surveys provided empirical support for a relationship between sociodemographic characteristics and capacity to assess and mitigate exposures to potentially contaminated water. Further research is needed to probe if the observed disparities translate to differences in chemical exposure and adverse health outcomes.
Data Assimilation Networks
Authors: Boudier Pierre , Fillion Anthony , Gratton Serge , Gürol Selime , Zhang Sixin
Published: April 2023

Data Assimilation aims at estimating the posterior conditional probability density functions based on error statistics of the noisy observations and the dynamical system. State of the art methods are sub‐optimal due to the common use of Gaussian error statistics and the linearization of the non‐linear dynamics. To achieve a good performance, these methods often require case‐by‐case fine‐tuning by using explicit regularization techniques such as inflation and localization. In this paper, we propose a fully data driven deep learning framework generalizing recurrent Elman networks and data assimilation algorithms. Our approach approximates a sequence of prior and posterior densities conditioned on noisy observations using a log‐likelihood cost function. By construction our approach can then be used for general nonlinear dynamics and non‐Gaussian densities. As a first step, we evaluate the performance of the proposed approach by using fully and partially observed Lorenz‐95 system in which the outputs of the recurrent network are fitted to Gaussian densities. We numerically show that our approach, without using any explicit regularization technique, achieves comparable performance to the state‐of‐the‐art methods, IEnKF‐Q and LETKF, across various ensemble size.
Wildfire Smoke Destroys Ozone
Authors: Cutts Elise
Published: April 2023

Smoke aerosols from large wildfires are the perfect reaction surface for chlorine chemicals, speeding their transformation from ozone-friendly forms to reactive ones.
UAS‐Based Observations of Infrasound Directionality at Stromboli Volcano, Italy
Authors: Iezzi Alexandra M. , Buzard Richard M. , Fee David , Matoza Robin S. , Gestrich Julia E. , Jolly Arthur D. , Schmid Markus , Cigala Valeria , Kueppers Ulrich , Vossen Caron E. J. , Cimarelli Corrado , Lacanna Giorgio , Ripepe Maurizio
Published: April 2023

Infrasound (low frequency sound waves) can be used to monitor and characterize volcanic eruptions. However, infrasound sensors are usually placed on the ground, thus providing a limited sampling of the acoustic radiation pattern that can bias source size estimates. We present observations of explosive eruptions from a novel uncrewed aircraft system (UAS)‐based infrasound sensor platform that was strategically hovered near the active vents of Stromboli volcano, Italy. We captured eruption infrasound from short‐duration explosions and jetting events. While potential vertical directionality was inconclusive for the short‐duration explosion, we find that jetting events exhibit vertical sound directionality that was observed with a UAS close to vertical. This directionality would not have been observed using only traditional deployments of ground‐based infrasound sensors, but is consistent with jet noise theory. This proof‐of‐concept study provides unique information that can improve our ability to characterize and quantify the directionality of volcanic eruptions and their associated hazards.
Diurnal Cycle of Wind Speed and Precipitation Over the Northern Australia Coastal Region: CYGNSS Observations
Authors: Bui Hien X. , Maloney Eric D. , Short Ewan , Riley Dellaripa Emily M.
Published: April 2023

The diurnal cycle of precipitation and its associated land‐sea breeze circulation over coastal northern Australia are investigated using surface wind speed and enthalpy (latent and sensible heat) fluxes from the Cyclone Global Navigation Satellite System. Composite results during the austral summer of 2018–2022 show that diurnal precipitation propagates westward from the Cape York Peninsula into the Gulf of Carpentaria. The diurnal cycle of precipitation and surface wind speed are strongly coupled, with the wind speed maximum slightly leading the precipitation maximum. Additionally, analysis of the moist static energy budget shows that surface fluxes help support the westward‐propagation of diurnal precipitation. These results—based on novel satellite data and reanalysis—are consistent with previous studies that have examined the impact of the land‐sea breeze on the diurnal cycle of precipitation. The results provide a benchmark for model representation of this important atmosphere‐ocean‐land interaction.
Scattering of Radiation Belt Electrons by Fast Magnetosonic Waves: Considering the Kinetic Effects
Authors: Yao Fei , Liu Kaijun , Yu Xiongdong , Wang Yan , Xiong Ying , Zhang Shuai
Published: April 2023

When assessing the scattering of radiation belt electrons by fast magnetosonic (MS) waves, it is traditionally assumed that the waves follow the MS/whistler branch of the cold plasma dispersion relation (CPDR) in magnetohydrodynamics. However, MS waves are essentially ion Bernstein modes following a distinct kinetic dispersion relation. This study calculates the MS wave‐induced electron diffusion rates with the kinetic dispersion relation for the first time and compares the results with that obtained with the CPDR. It is found that the kinetic effects lead to a lower minimum resonant energy around 100 eV and a broader resonant pitch angle range. Kinetic effects also result in power spectral density attenuation when transforming wave frequency spectra into wavenumber spectra, so the diffusion rates are overall smaller than the ones obtained using the CPDR. Our results demonstrate that kinetic effects can significantly affect the role that MS waves play in the radiation belt dynamics.
Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors
Authors: Kovács Szonja Anna , Fekete János Tibor , Győrffy Balázs
Published: April 2023

Immune-checkpoint inhibitors show promising effects in the treatment of multiple tumor types. Biomarkers are biological indicators used to select patients for a systemic anticancer treatment, but there are only a few clinically useful biomarkers such as PD-L1 expression and tumor mutational burden, which can be used to predict immunotherapy response. In this study, we established a database consisting of both gene expression and clinical data to identify biomarkers of response to anti-PD-1, anti-PD-L1, and anti-CTLA-4 immunotherapies. A GEO screening was executed to identify datasets with simultaneously available clinical response and transcriptomic data regardless of cancer type. The screening was restricted to the studies involving administration of anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab) or anti-CTLA-4 (ipilimumab) agents. Receiver operating characteristic (ROC) analysis and Mann-Whitney test were executed across all genes to identify features related to therapy response. The database consisted of 1434 tumor tissue samples from 19 datasets with esophageal, gastric, head and neck, lung, and urothelial cancers, plus melanoma. The strongest druggable gene candidates linked to anti-PD-1 resistance were SPIN1 (AUC = 0.682, P = 9.1E-12), SRC (AUC = 0.667, P = 5.9E-10), SETD7 (AUC = 0.663, P = 1.0E-09), FGFR3 (AUC = 0.657, P = 3.7E-09), YAP1 (AUC = 0.655, P = 6.0E-09), TEAD3 (AUC = 0.649, P = 4.1E-08) and BCL2 (AUC = 0.634, P = 9.7E-08). In the anti-CTLA-4 treatment cohort, BLCAP (AUC = 0.735, P = 2.1E-06) was the most promising gene candidate. No therapeutically relevant target was found to be predictive in the anti-PD-L1 cohort. In the anti-PD-1 group, we were able to confirm the significant correlation with survival for the mismatch-repair genes MLH1 and MSH6. A web platform for further analysis and validation of new biomarker candidates was set up and available at https://www.rocplot.com/immune. In summary, a database and a web platform were established to investigate biomarkers of immunotherapy response in a large cohort of solid tumor samples. Our results could help to identify new patient cohorts eligible for immunotherapy.
Quantifying requirements for mitochondrial apoptosis in CAR T killing of cancer cells
Authors: Pourzia Alexandra L. , Olson Michael L. , Bailey Stefanie R. , Boroughs Angela C. , Aryal Aditi , Ryan Jeremy , Maus Marcela V. , Letai Anthony
Published: April 2023

Chimeric antigen receptor (CAR) T cell therapy is an FDA-approved treatment for several hematologic malignancies, yet not all patients respond to this treatment. While some resistance mechanisms have been identified, cell death pathways in target cancer cells remain underexplored. Impairing mitochondrial apoptosis via knockout of Bak and Bax, forced Bcl-2 and Bcl-XL expression, or caspase inhibition protected several tumor models from CAR T killing. However, impairing mitochondrial apoptosis in two liquid tumor cell lines did not protect target cells from CAR T killing. We found that whether a cell was Type I or Type II in response to death ligands explained the divergence of these results, so that mitochondrial apoptosis was dispensable for CART killing of cells that were Type I but not Type II. This suggests that the apoptotic signaling induced by CAR T cells bears important similarities to that induced by drugs. Combinations of drug and CAR T therapies will therefore require tailoring to the specific cell death pathways activated by CAR T cells in different types of cancer cells.
A lncRNA from an inflammatory bowel disease risk locus maintains intestinal host-commensal homeostasis
Authors: Ma Hongdi , Hu Taidou , Tao Wanyin , Tong Jiyu , Han Zili , Herndler-Brandstetter Dietmar , Wei Zheng , Liu Ruize , Zhou Tingyue , Liu Qiuyuan , Xu Xuemei , Zhang Kaiguang , Zhou Rongbin , Cho Judy H. , Li Hua-Bing , Huang Hailiang , Flavell Richard A. , Zhu Shu
Published: April 2023

Inflammatory bowel diseases (IBD) are known to have complex, genetically influenced etiologies, involving dysfunctional interactions between the intestinal immune system and the microbiome. Here, we characterized how the RNA transcript from an IBD-associated long non-coding RNA locus (“CARINH-Colitis Associated IRF1 antisense Regulator of Intestinal Homeostasis”) protects against IBD. We show that CARINH and its neighboring gene coding for the transcription factor IRF1 together form a feedforward loop in host myeloid cells. The loop activation is sustained by microbial factors, and functions to maintain the intestinal host-commensal homeostasis via the induction of the anti-inflammatory factor IL-18BP and anti-microbial factors called guanylate-binding proteins (GBPs). Extending these mechanistic insights back to humans, we demonstrate that the function of the CARINH/IRF1 loop is conserved between mice and humans. Genetically, the T allele of rs2188962, the most probable causal variant of IBD within the CARINH locus from the human genetics study, impairs the inducible expression of the CARINH/IRF1 loop and thus increases genetic predisposition to IBD. Our study thus illustrates how an IBD-associated lncRNA maintains intestinal homeostasis and protects the host against colitis.
Histopathology images predict multi-omics aberrations and prognoses in colorectal cancer patients
Authors: Tsai Pei-Chen , Lee Tsung-Hua , Kuo Kun-Chi , Su Fang-Yi , Lee Tsung-Lu Michael , Marostica Eliana , Ugai Tomotaka , Zhao Melissa , Lau Mai Chan , Väyrynen Juha P. , Giannakis Marios , Takashima Yasutoshi , Kahaki Seyed Mousavi , Wu Kana , Song Mingyang , Meyerhardt Jeffrey A. , Chan Andrew T. , Chiang Jung-Hsien , Nowak Jonathan , Ogino Shuji , Yu Kun-Hsing
Published: April 2023

Histopathologic assessment is indispensable for diagnosing colorectal cancer (CRC). However, manual evaluation of the diseased tissues under the microscope cannot reliably inform patient prognosis or genomic variations crucial for treatment selections. To address these challenges, we develop the Multi-omics Multi-cohort Assessment (MOMA) platform, an explainable machine learning approach, to systematically identify and interpret the relationship between patients’ histologic patterns, multi-omics, and clinical profiles in three large patient cohorts (n = 1888). MOMA successfully predicts the overall survival, disease-free survival (log-rank test P-value<0.05), and copy number alterations of CRC patients. In addition, our approaches identify interpretable pathology patterns predictive of gene expression profiles, microsatellite instability status, and clinically actionable genetic alterations. We show that MOMA models are generalizable to multiple patient populations with different demographic compositions and pathology images collected from distinctive digitization methods. Our machine learning approaches provide clinically actionable predictions that could inform treatments for colorectal cancer patients.
Integrated model of the vertebrate augmin complex
Authors: Travis Sophie M. , Mahon Brian P. , Huang Wei , Ma Meisheng , Rale Michael J. , Kraus Jodi , Taylor Derek J. , Zhang Rui , Petry Sabine
Published: April 2023

Accurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which rapidly amplifies microtubules during cell division. Branching microtubule nucleation relies on the hetero-octameric augmin complex, but lack of structure information about augmin has hindered understanding how it promotes branching. In this work, we combine cryo-electron microscopy, protein structural prediction, and visualization of fused bulky tags via negative stain electron microscopy to identify the location and orientation of each subunit within the augmin structure. Evolutionary analysis shows that augmin’s structure is highly conserved across eukaryotes, and that augmin contains a previously unidentified microtubule binding site. Thus, our findings provide insight into the mechanism of branching microtubule nucleation.
The pace of shifting seasons in lakes
Authors: Woolway R. Iestyn
Published: April 2023

Lake ecosystems are vulnerable to seasonal thermal cues, with subtle alterations in the timing of seasonal temperatures having a dramatic influence on aquatic species. Here, a measure of seasonal change in temperature is used to describe the pace of shifting seasons in lakes. Since 1980 spring and summer temperatures in Northern Hemisphere lakes have arrived earlier (2.0- and 4.3-days decade−1, respectively), whilst the arrival of autumn has been delayed (1.5-days decade−1) and the summer season lengthened (5.6-days decade−1). This century, under a high-greenhouse-gas-emission scenario, current spring and summer temperatures will arrive even earlier (3.3- and 8.3-days decade−1, respectively), autumn temperatures will arrive later (3.1-days decade−1), and the summer season will lengthen further (12.1-days decade−1). These seasonal alterations will be much slower under a low-greenhouse-gas-emission scenario. Changes in seasonal temperatures will benefit some species, by prolonging the growing season, but negatively impact others, by leading to phenological mismatches in critical activities.
East Gobi megalake systems reveal East Asian Monsoon dynamics over the last interglacial-glacial cycle
Authors: Li Hongwei , Yang Xiaoping , Scuderi Louis Anthony , Hu Fangen , Liang Peng , Jiang Qida , Buylaert Jan-Pieter , Wang Xulong , Du Jinhua , Kang Shugang , Ma Zhibang , Wang Lisheng , Wang Xuefeng
Published: April 2023

Intense debate persists about the timing and magnitude of the wet phases in the East Asia deserts since the late Pleistocene. Here we show reconstructions of the paleohydrology of the East Gobi Desert since the last interglacial using satellite images and digital elevation models (DEM) combined with detailed section analyses. Paleolakes with a total area of 15,500 km2during Marine Isotope Stage 5 (MIS 5) were identified. This expanded lake system was likely coupled to an 800–1000 km northward expansion of the humid region in East China, associated with much warmer winters. Humid climate across the Gobi Desert during MIS 5 likely resulted in a dustier MIS 4 over East Asia and the North Pacific. A second wet period characterized by an expanded, albeit smaller, lake area is dated to the mid-Holocene. Our results suggest that the East Asian Summer Monsoon (EASM) might have been much weaker during MIS 3.
Ultra-high-resolution observations of persistent null-point reconnection in the solar corona
Authors: Cheng X. , Priest E. R. , Li H. T. , Chen J. , Aulanier G. , Chitta L. P. , Wang Y. L. , Peter H. , Zhu X. S. , Xing C. , Ding M. D. , Solanki S. K. , Berghmans D. , Teriaca L. , Aznar Cuadrado R. , Zhukov A. N. , Guo Y. , Long D. , Harra L. , Smith P. J. , Rodriguez L. , Verbeeck C. , Barczynski K. , Parenti S.
Published: April 2023

Magnetic reconnection is a key mechanism involved in solar eruptions and is also a prime possibility to heat the low corona to millions of degrees. Here, we present ultra-high-resolution extreme ultraviolet observations of persistent null-point reconnection in the corona at a scale of about 390 km over one hour observations of the Extreme-Ultraviolet Imager on board Solar Orbiter spacecraft. The observations show formation of a null-point configuration above a minor positive polarity embedded within a region of dominant negative polarity near a sunspot. The gentle phase of the persistent null-point reconnection is evidenced by sustained point-like high-temperature plasma (about 10 MK) near the null-point and constant outflow blobs not only along the outer spine but also along the fan surface. The blobs appear at a higher frequency than previously observed with an average velocity of about 80 km s−1and life-times of about 40 s. The null-point reconnection also occurs explosively but only for 4 minutes, its coupling with a mini-filament eruption generates a spiral jet. These results suggest that magnetic reconnection, at previously unresolved scales, proceeds continually in a gentle and/or explosive way to persistently transfer mass and energy to the overlying corona.
Serum but not cerebrospinal fluid levels of allantoin are increased in de novo Parkinson’s disease
Authors: Hasíková Lenka , Závada Jakub , Serranová Tereza , Kozlík Petr , Kalíková Květa , Kotačková Lenka , Trnka Jiří , Zogala David , Šonka Karel , Růžička Evžen , Dušek Petr
Published: April 2023

Oxidative stress supposedly plays a role in the pathogenesis of Parkinson’s disease (PD). Uric acid (UA), a powerful antioxidant, is lowered in PD while allantoin, the oxidation product of UA and known biomarker of oxidative stress, was not systematically studied in PD. We aim to compare serum and cerebrospinal fluid (CSF) levels of UA, allantoin, and allantoin/UA ratio in de novo PD patients and controls, and evaluate their associations with clinical severity and the degree of substantia nigra degeneration in PD. We measured serum and CSF levels of UA, allantoin, and allantoin/UA ratio in 86 PD patients (33 females, mean age 57.9 (SD 12.6) years; CSF levels were assessed in 51 patients) and in 40 controls (19 females, 56.7 (14.1) years). PD patients were examined using Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson Disease-Autonomic (SCOPA-AUT), the University of Pennsylvania Smell Identification Test (UPSIT), one-night video-polysomnography, and dopamine transporter single-photon emission computed tomography (DAT-SPECT). Serum allantoin and allantoin/UA ratio were significantly increased in the PD group compared to controls (p < 0.001 and p = 0.002, respectively). Allantoin/UA ratios in serum and CSF were positively associated with the SCOPA-AUT score (p = 0.005 and 0.031, respectively) and RBD presence (p = 0.044 and 0.028, respectively). In conclusion, serum allantoin and allantoin/UA ratio are elevated in patients with de novo PD. Allantoin/UA ratio in serum and CSF is associated with autonomic dysfunction and RBD presence, indicating that higher systemic oxidative stress occurs in PD patients with more diffuse neurodegenerative changes.
Scaling and intermittency in turbulent flows of elastoviscoplastic fluids
Authors: Abdelgawad Mohamed S. , Cannon Ianto , Rosti Marco E.
Published: April 2023

Non-Newtonian fluids have a viscosity that varies with applied stress. Elastoviscoplastic fluids, the elastic, viscous and plastic properties of which are interconnected in a non-trivial way, belong to this category. We have performed numerical simulations to investigate turbulence in elastoviscoplastic fluids at very high Reynolds-number values, as found in landslides and lava flows, focusing on the effect of plasticity. We find that the range of active scales in the energy spectrum reduces when increasing the fluid plasticity; when plastic effects dominate, a new scaling range emerges between the inertial range and the dissipative scales. An extended self-similarity analysis of the structure functions reveals that intermittency is present and grows with the fluid plasticity. The enhanced intermittency is caused by the non-Newtonian dissipation rate, which also exhibits an intermittent behaviour. These findings have relevance to catastrophic events in natural flows, such as landslides and lava flows, where the enhanced intermittency results in stronger extreme events, which are thus more destructive and difficult to predict.
Interactome dynamics of RAF1-BRAF kinase monomers and dimers
Authors: Iglesias-Martinez Luis F. , Rauch Nora , Wynne Kieran , McCann Brendan , Kolch Walter , Rauch Jens
Published: April 2023

RAF kinases play major roles in cancer. BRAFV600E mutants drive ~6% of human cancers. Potent kinase inhibitors exist but show variable effects in different cancer types, sometimes even inducing paradoxical RAF kinase activation. Both paradoxical activation and drug resistance are frequently due to enhanced dimerization between RAF1 and BRAF, which maintains or restores the activity of the downstream MEK-ERK pathway. Here, using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers identifying and quantifying >1,000 proteins. In addition, we examined the effects of vemurafenib and sorafenib, two different types of clinically used RAF inhibitors. Using regression analysis to compare different conditions we found a large overlapping core interactome but also distinct condition specific differences. Given that RAF proteins have kinase independent functions such dynamic interactome changes could contribute to their functional diversification. Analysing this dataset may provide a deeper understanding of RAF signalling and mechanisms of resistance to RAF inhibitors.
Establishment of an artificial particulate matter-induced lung disease model through analyzing pathological changes and transcriptomic profiles in mice
Authors: Kim Dong Im , Song Mi-Kyung , Yuk Ji Eun , Seo Hyeon Jin , Lee Kyuhong
Published: April 2023

Particulate matter (PM), an environmental risk factor, is linked with health risks such as respiratory diseases. This study aimed to establish an animal model of PM-induced lung injury with artificial PM (APM) and identify the potential of APM for toxicological research. APM was generated from graphite at 600 °C and combined with ethylene. We analyzed diesel exhaust particulate (DEP) and APM compositions and compared toxicity and transcriptomic profiling in lungs according to the exposure. For the animal study, C57BL/6 male mice were intratracheally administered vehicle, DEP, or APM. DEP or APM increased relative lung weight, inflammatory cell numbers, and inflammatory protein levels compared with the vehicle control. Histological assessments showed an increase in particle-pigment alveolar macrophages and slight inflammation in the lungs of DEP and APM mice. In the only APM group, granulomatous inflammation, pulmonary fibrosis, and mucous hyperplasia were observed in the lungs of some individuals. This is the first study to compare pulmonary toxicity between DEP and APM in an animal model. Our results suggest that the APM-treated animal model may contribute to understanding the harmful effects of PM in toxicological studies showing that APM can induce various lung diseases according to different doses of APM.
Large-scale effects of offshore wind farms on seabirds of high conservation concern
Authors: Garthe Stefan , Schwemmer Henriette , Peschko Verena , Markones Nele , Müller Sabine , Schwemmer Philipp , Mercker Moritz
Published: April 2023

The North Sea is a key area worldwide for the installation of offshore wind farms (OWFs). We analysed data from multiple sources to quantify the effects of OWFs on seabirds from the family Gaviidae (loons) in the German North Sea. The distribution and abundance of loons changed substantially from the period before to the period after OWF construction. Densities of loons were significantly reduced at distances of up to 9–12 km from the OWF footprints. Abundance declined by 94% within the OWF + 1 km zone and by 52% within the OWF + 10 km zone. The observed redistribution was a large-scale effect, with birds aggregating within the study area at large distances from the OWFs. Although renewable energies will be needed to provide a large share of our energy demands in the future, it is necessary to minimize the costs in terms of less-adaptable species, to avoid amplifying the biodiversity crisis.
An interpretable and interactive deep learning algorithm for a clinically applicable retinal fundus diagnosis system by modelling finding-disease relationship
Authors: Son Jaemin , Shin Joo Young , Kong Seo Taek , Park Jeonghyuk , Kwon Gitaek , Kim Hoon Dong , Park Kyu Hyung , Jung Kyu-Hwan , Park Sang Jun
Published: April 2023

The identification of abnormal findings manifested in retinal fundus images and diagnosis of ophthalmic diseases are essential to the management of potentially vision-threatening eye conditions. Recently, deep learning-based computer-aided diagnosis systems (CADs) have demonstrated their potential to reduce reading time and discrepancy amongst readers. However, the obscure reasoning of deep neural networks (DNNs) has been the leading cause to reluctance in its clinical use as CAD systems. Here, we present a novel architectural and algorithmic design of DNNs to comprehensively identify 15 abnormal retinal findings and diagnose 8 major ophthalmic diseases from macula-centered fundus images with the accuracy comparable to experts. We then define a notion of counterfactual attribution ratio (CAR) which luminates the system’s diagnostic reasoning, representing how each abnormal finding contributed to its diagnostic prediction. By using CAR, we show that both quantitative and qualitative interpretation and interactive adjustment of the CAD result can be achieved. A comparison of the model’s CAR with experts’ finding-disease diagnosis correlation confirms that the proposed model identifies the relationship between findings and diseases similarly as ophthalmologists do.