bluuebunny/crossref_metadata_2025 huggingface dataset:
Voicing their choices: Advance care planning with adolescents and young adults with cancer and other serious conditions
Authors: Wiener Lori , Bedoya Sima , Battles Haven , Sender Leonard , Zabokrtsky Keri , Donovan Kristine A. , Thompson Lora M. A. , Lubrano di Ciccone Barbara B. , Babilonia Margarita Bobonis , Fasciano Karen , Malinowski Paige , Lyon Maureen , Thompkins Jessica , Heath Corey , Velazquez Denise , Long-Traynor Karen , Fry Abigail , Pao Maryland
Published: December 2021

Objectives

To determine whether engaging in advance care planning (ACP) using a formal tool, Voicing My CHOiCES (VMC), would alleviate adolescent and young adults (AYAs) anxiety surrounding ACP and increase social support and communication about end-of-life care preferences with family members and health care providers (HCPs).

Methods

A total of 149 AYAs aged 18–39 years receiving cancer-directed therapy or treatment for another chronic medical illness were enrolled at seven US sites. Baseline data included prior ACP communication with family members and HCPs and measures of generalized anxiety, ACP anxiety, and social support. Participants critically reviewed each page of VMC and then completed three pages of the document. ACP anxiety was measured again immediately after the completion of VMC pages. One month later, participants repeated anxiety and social support measures and were asked if they shared what they had completed in VMC with a family member or HCP.

Results

At baseline, 50.3% of participants reported that they previously had a conversation about EoL preferences with a family member; 19.5% with an HCP. One month later, 65.1% had subsequently shared what they wrote in VMC with a family member; 8.9% shared with an HCP. Most (88.6%) reported they would not have had this conversation if not participating in the study. No significant changes occurred in social support. There was an immediate drop in anxiety about EoL planning after reviewing VMC which persisted at 1 month. Generalized anxiety was also significantly lower 1 month after reviewing VMC.

Significance of results

Having a document specifically created for AYAs to guide ACP planning can decrease anxiety and increase communication with family members but not necessarily with HCPs. Future research should examine ways ACP can be introduced more consistently to this young population to allow their preferences for care to be heard, respected, and honored, particularly by their healthcare providers.
Estimation of intrapulse modulation parameters of LPI radar under noisy conditions
Authors: Raja Kumari Chilukuri , Kakarla Hari Kishore , Subbarao K.
Published: December 2021

Low probability of intercept (LPI) radars utilize specially designed waveforms for intra-pulse modulation and hence LPI radars cannot be easily intercepted by passive receivers. The waveforms include linear frequency modulation, nonlinear frequency modulation, polyphase, and polytime codes. The advantages of LPI radar are wide bandwidth, frequency variability, low power, and the ability to hide their emissions. On the other hand, the main purpose of intercept receiver is to classify and estimate the parameters of the waveforms even when the signals are contaminated with noise. Precise measurement of the parameters will provide necessary information about a threat to the radar so that the electronic attack or electronic warfare support system could take instantaneous counter action against the enemy. In this work, noisy polyphase and polytime coded waveforms are analyzed using cyclostationary (CS) algorithm. To improve the signal quality, the noisy signal is pre-processed using two types of denoising filters. The denoised signal is analyzed using CS techniques and the coefficients of spectral correlation density are computed. With this method, modulation parameters of nine types of waveforms up to −12 dB signal-to-noise ratio with an accuracy of better than 95% are extracted. When compared with literature values, it is found that the results are superior.
Sex specific associations between in utero exposure to persistent organic pollutants and allergy-related outcomes in childhood: The Rhea Mother–Child Cohort (Crete, Greece)
Authors: Margetaki Katerina , Alexaki Maria , Vittorakis Evangelos , Roumeliotaki Theano , Leventakou Vasiliki , Bempi Vicky , Chalkiadaki Georgia , Kyrtopoulos Soterios A. , Rantakokko Panu , Kiviranta Hannu , Stephanou Euripides G. , Kogevinas Manolis , Chatzi Leda , Vafeiadi Marina
Published: December 2021

Accumulating evidence suggests that in utero exposures can influence the development of the immune system. Few studies have investigated whether prenatal exposure to persistent organic pollutants (POPs) is associated with allergy-related phenotypes in childhood, nor explored sex differences. We examined the association between prenatal exposure to POPs and offspring allergic outcomes in early and mid-childhood. We included 682 mother–child pairs from the prospective birth cohort Rhea. We measured dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and 6 polychlorinated biphenyl (PCB) congeners in maternal first trimester serum. Parents completed the questionnaires adapted from the International Study on Asthma and Allergy in Childhood (ISAAC) for allergy-related phenotypes when their children were 4 and 6 years old. We used Poisson regression models to estimate Risk Ratios. Prenatal HCB was associated with increased risk for rhinoconjunctivitis at 6 years (RR (95% CI): 2.5; (1.3, 4.8) for a doubling in the exposure). Among girls, prenatal DDE was associated with increased risk for current wheeze, current asthma and current rhinoconjunctivitis at 4 years (RR (95%CI): 1.4 (0.8, 2.6), 1.6 (1.1, 2.4) and 1.8 (1.0, 3.3) and p-interaction = 0.035, 0.027 and 0.059, respectively), with increased risk for current rhinoconjunctivitis at 6 years (RR (95%CI): 1.7 (0.7, 3.8) and p-interaction = 0.028) and total PCBs were associated with increased risk for current eczema at 4 years (RR (95%CI): 2.1 (1.1, 4.2) and p-interaction = 0.028). In boys, prenatal DDE was associated with decreased risk for current wheeze and current asthma at 4 years. Our findings suggest that even low levels of exposure to POPs prenatally may affect the development of childhood allergy-related outcomes in a sex and age-specific manner.
Wahrgenommene Wertschätzung im Lehramtsstudium
Authors: Carstensen Bastian , Lindner Christoph , Klusmann Uta
Published: December 2021

Zusammenfassung. Die wahrgenommene Wertschätzung stellt nicht nur im Arbeits- sondern auch im Hochschulkontext eine wichtige soziale Ressource für die akademische Leistung, das Engagement und Wohlbefinden dar. Studentinnen und Studenten, die sich in ihren Lehrveranstaltungen wertgeschätzt fühlen, lernen erfolgreicher und neigen seltener zu Studienabbruchsintentionen. Erste Untersuchungen zeigen, dass Studentinnen und Studenten mit dem Abschlussziel Lehramt sich im Vergleich zu Fachstudentinnen und -studenten weniger von ihren Dozentinnen und Dozenten wertgeschätzt fühlen, allerdings kontrollieren diese Studien nicht für intraindividuelle Unterschiede zwischen den Studienfächern. Vor diesem Hintergrund haben wir untersucht, wie sich N = 1255 Lehramtsstudentinnen und -studenten in ihren zwei Studienfächern hinsichtlich ihrer Kompetenzen wertgeschätzt fühlen und welche personenbezogenen und fachspezifischen Faktoren die wahrgenommene Wertschätzung beeinflussen. Die Ergebnisse der mehrebenanalytischen Modelle zeigten, dass die wahrgenommene Wertschätzung durch die Dozentinnen und Dozenten vor allem auf Ebene der studierten Fächer variierte, wobei in der MINT-Fächergruppe weniger Wertschätzung wahrgenommen wurde. Zweitens haben wir anhand einer längsschnittlichen Substichprobe ( N = 436) untersucht, inwieweit die wahrgenommene Wertschätzung mit Indikatoren des Wohlbefindens, der Studienabbruchsintention sowie Veränderungen in diesen Outcomes im Verlauf eines Jahres assoziiert ist. Anhand der Ergebnisse zeigte sich, dass Studentinnen und Studenten, die sich mehr wertgeschätzt fühlten, auch zufriedener mit ihrem Studium und ihren Lehrveranstaltungen waren, mehr Fachenthusiasmus berichteten, weniger erschöpft waren und seltener zu Studienabbruchsintentionen neigten. Zusätzlich war die wahrgenommene Wertschätzung mit der Veränderung in diesen Outcomes assoziiert. Die Befunde werden vor dem Hintergrund praktischer Problemfelder wie dem Lehrkräftemangel diskutiert.
The Adaptation of a Measure of Confidence in Assessing, Formulating, and Managing Suicide Risk
Authors: Sandford David M. , Kirtley Olivia J. , Thwaites Richard , Dagnan Dave , O'Connor Rory C.
Published: December 2021

Abstract. Background: To date little has been done to evaluate the effectiveness of suicide risk formulation training. Aims: We aimed to investigate the psychometric properties of a new scale measuring clinicians' confidence in assessing, formulating, and managing suicide risk. Method: A total of 128 mental health practitioners from an UK National Health Service Trust completed the scale. Of them, 85 from an Improving Access to Psychological Therapies service did so before and after training in Risk Assessment, Formulation, and Management (RAFM); 28 practitioners from the Older Adults service also completed the measure. For test–retest analysis, a further 15 completed the scale again 1 week after baseline without attending any training. Of the training group, 52 (61%) completed the measure at the 6-month follow-up. Results: Analysis indicated a single-factor structure, good test–retest reliability, and statistically significant increases in confidence between pre- and posttraining and between pretraining and 6 month follow-up. Cohen's effect size values suggest a moderate-to-large effect. Limitations: The relatively small sample sizes indicate that this study should be considered a preliminary investigation of a new measure, which warrants further replication. Conclusion: This measure could be useful in gauging practitioners' confidence in the RAFM approach and in evaluating and developing training.
Resilience to Self-Harm
Authors: Khan Anam , Ungar Michael
Published: December 2021

Abstract. Background: Although a wide range of studies discuss prevalence and risk factors associated with self-harm, protective factors that are equally important are rarely explored. Moreover, much of our understanding of young individuals who engage in self-harm come from studies conducted in Western countries with very little emphasis on marginalized groups. Aim: This scoping review identifies research on resilience among marginalized youth and youth living in low- and middle-income countries (LMICs) who show evidence of self-harm. Method: A scoping review following Arksey and O’Malley’s (2005) framework was conducted. This effort included drawing upon peer-reviewed research published between January 2000 and September 2020 to identify protective factors and coping strategies that are employed by individuals 10–29 years old with self-harming tendencies. Results: A total of 15 original papers met the inclusion criteria. The majority of the LMIC publications were from China. Social support, positive youth development, and religiosity were the most frequently reported protective factors. Conclusion: Despite widespread concern about self-harm, there are few peer-reviewed articles that look at resilience or recovery among youth in LMICs and among marginalized young people. In addition to various internal and external protective factors, this scoping review identifies gaps in our understanding of resilience to self-harm among youth belonging to these groups.
The Impact of the COVID-19 Pandemic on Suicide Rate Trends in the Tsunami-Disaster-Affected Area Following the Great East Japan Earthquake
Authors: Orui Masatsugu , Saeki Suzuka , Kozakai Yuki , Harada Shuichiro , Hayashi Mizuho
Published: December 2021

Abstract: Background: People who experienced the Great East Japan Earthquake (GEJE) were expected to have additional levels of psychological burden resulting from the stressful conditions imposed during the coronavirus disease 2019 (COVID-19) pandemic; consequently, suicide rates may increase. Aim: We aimed to carry out continuous monitoring of suicide rates in the affected area following the GEJE under COVID-19 pandemic conditions. Method: This descriptive study monitored the suicide rates of the coastal area of Miyagi Prefecture, where disaster-related mental health activities have been continuing following severe damage caused by the tsunami disaster. An exponential smoothing time-series analysis that converted suicide rates into a smooth trend was conducted. Results: Although the suicide rate in the affected area was higher than the national average in February 2020, it showed a declining trend during the COVID-19 pandemic, while showing an increase trend in the national and non-affected areas. Limitations: Uncertainty about the direct reasons for suicide and the short time-scale observation are the limitations of this study. Conclusion: Although the national suicide rate increased, this was not the case for the affected area. Our findings may provide important lessons for suicide prevention during the COVID-19 pandemic, which needs careful regional monitoring of the state of suicide and of high-risk approaches such as disaster-related mental health activities.
Global Groundwater Modeling and Monitoring: Opportunities and Challenges
Authors: Condon Laura E. , Kollet Stefan , Bierkens Marc F. P. , Fogg Graham E. , Maxwell Reed M. , Hill Mary C. , Fransen Harrie‐Jan Hendricks , Verhoef Anne , Van Loon Anne F. , Sulis Mauro , Abesser Corinna
Published: December 2021

Groundwater is by far the largest unfrozen freshwater resource on the planet. It plays a critical role as the bottom of the hydrologic cycle, redistributing water in the subsurface and supporting plants and surface water bodies. However, groundwater has historically been excluded or greatly simplified in global models. In recent years, there has been an international push to develop global scale groundwater modeling and analysis. This progress has provided some critical first steps. Still, much additional work will be needed to achieve a consistent global groundwater framework that interacts seamlessly with observational datasets and other earth system and global circulation models. Here we outline a vision for a global groundwater platform for groundwater monitoring and prediction and identify the key technological and data challenges that are currently limiting progress. Any global platform of this type must be interdisciplinary and cannot be achieved by the groundwater modeling community in isolation. Therefore, we also provide a high‐level overview of the groundwater system, approaches to groundwater modeling and the current state of global groundwater representations, such that readers of all backgrounds can engage in this challenge.
Geoscientists Can Help Reduce the Threat of Nuclear Weapons
Authors: Robock Alan , Prager Stewart
Published: December 2021

A nuclear war would claim many lives from its direct impacts and cause rapid climate change that would further imperil humanity. Scientists can help shape policies to put us on a safer path.
Comparison of Different Coupling Methods for Joint Inversion of Geophysical Data: A Case Study for the Namibian Continental Margin
Authors: Franz G. , Moorkamp M. , Jegen M. , Berndt C. , Rabbel W.
Published: December 2021

Integration of multiple geophysical data is a key practice to reduce model uncertainties and enhance geological interpretations. Electrical resistivity models resulting from inversion of marine magnetotelluric (MT) data, often lack depth resolution of lithological boundaries and distinct information for shallow model parts. This is due to the diffusive nature of electromagnetic fields, enhanced by deficient data sampling and model regularization during inversion. Thus, integrating data or models to constrain layer thicknesses or structural boundaries is an effective approach to derive better constrained and more detailed resistivity models. We investigate the different impacts of three cross‐gradient coupled constraints on 3D MT inversion of data from the Namibian passive continental margin. The three constraints are (a) coupling with a fixed structural density model; (b) coupling with satellite gravity data; (c) coupling with a fixed gradient velocity model. Here, we show that coupling with a fixed model (a and c) improves the resistivity model the most. Shallow conductors imaging sediment cover are confined to a thinner layer in the resulting resistivity models compared to the MT‐only model. Additionally, these constraints help to suppress vertical smearing of a conductive anomaly attributed to a fracture zone, and clearly show that the seismically imaged Moho is not accompanied by a change in electrical resistivity. All of these observations help to derive an Earth model, which will form the basis for future interpretation of the processes that lead to continental break‐up during the early Cretaceous.
Initial Results From the Oman Drilling Project Multi‐Borehole Observatory: Petrogenesis and Ongoing Alteration of Mantle Peridotite in the Weathering Horizon
Authors: Kelemen Peter B. , Leong James A. , Carlos de Obeso Juan , Matter Jürg M. , Ellison Eric T. , Templeton Alexis , Nothaft Daniel B. , Eslami Alireza , Evans Katy , Godard Marguerite , Malvoisin Benjamin , Coggon Jude A. , Warsi Nehal H. , Pézard Philippe , Choe Saebyul , Teagle Damon A. H. , Michibayashi Katsuyoshi , Takazawa Eiichi , Al Sulaimani Zaher ,   The Oman Drilling Project Science Team
Published: December 2021

The Oman Drilling Project “Multi‐Borehole Observatory” (MBO) samples an area of active weathering of tectonically exposed peridotite. This article reviews the geology of the MBO region, summarizes recent research, and provides new data constraining ongoing alteration. Host rocks are partially to completely serpentinized, residual mantle harzburgites, and replacive. Dunites show evidence for “reactive fractionation,” in which cooling, crystallizing magmas reacted with older residues of melting. Harzburgites and dunites are 65%–100% hydrated. Ferric to total iron ratios vary from 50% to 90%. In Hole BA1B, alteration extent decreases with depth. Gradients in water and core composition are correlated. Serpentine veins are intergrown with, and cut, carbonate veins with measurable14C. Ongoing hydration is accompanied by SiO2addition. Sulfur enrichment in Hole BA1B may result from oxidative leaching of sulfur from the upper 30 m, coupled with sulfate reduction and sulfide precipitation at 30–150 m. Oxygen fugacity deep in Holes BA3A, NSHQ14, and BA2A is fixed by the reaction 2H2O = 2H2 + O2combined with oxidation of ferrous iron in serpentine, brucite, and olivine. fO2deep in Holes BA1A, BA1D, and BA4A is 3–4 log units above the H2O‐H2limit, controlled by equilibria involving serpentine and brucite. Variations in alteration are correlated with texture, with reduced, low SiO2assemblages in mesh cores recording very low water/rock ratios, juxtaposed with adjacent veins recording much higher ratios. The proportion of reduced mesh cores versus oxidized veins increases with depth, and the difference in fO2recorded in cores and veins decreases with depth.
Single-cell analysis of salt-induced hypertensive mouse aortae reveals cellular heterogeneity and state changes
Authors: Zhang Ka , Kan Hao , Mao Aiqin , Geng Li , Ma Xin
Published: December 2021

Elevated blood pressure caused by excessive salt intake is common and associated with cardiovascular diseases in most countries. However, the composition and responses of vascular cells in the progression of hypertension have not been systematically described. We performed single-cell RNA sequencing on the aortic arch from C57BL/6J mice fed a chow/high-salt diet. We identified 19 distinct cell populations representing 12 lineages, including smooth muscle cells (SMCs), fibroblasts, endothelial cells (ECs), B cells, and T cells. During the progression of hypertension, the proportion of three SMC subpopulations, two EC subpopulations, and T cells increased. In two EC clusters, the expression of reactive oxygen species-related enzymes, collagen and contractility genes was upregulated. Gene set enrichment analysis showed that three SMC subsets underwent endothelial-to-mesenchymal transition. We also constructed intercellular networks and found more frequent cell communication among aortic cells in hypertension and that some signaling pathways were activated during hypertension. Finally, joint public genome-wide association study data and our single-cell RNA-sequencing data showed the expression of hypertension susceptibility genes in ECs, SMCs, and fibroblasts and revealed 21 genes involved in the initiation and development of high-salt-induced hypertension. In conclusion, our data illustrate the transcriptional landscape of vascular cells in the aorta associated with hypertension and reveal dramatic changes in cell composition and intercellular communication during the progression of hypertension.
Demonstration of thermal modulation using nanoscale and microscale structures for ultralarge pixel array photothermal transducers
Authors: Zhang Jinying , Li Defang , Li Zhuo , Wang Xin , Yang Suhui
Published: December 2021

Large-pixel-array infrared emitters are attractive in the applications of infrared imaging and detection. However, the array scale has been restricted in traditional technologies. Here, we demonstrated a light-driven photothermal transduction approach for an ultralarge pixel array infrared emitter. A metal-black coating with nanoporous structures and a silicon (Si) layer with microgap structures were proposed to manage the thermal input and output issues. The effects of the nanoscale structures in the black coating and microscale structures in the Si layer were investigated. Remarkable thermal modulation could be obtained by adjusting the nanoscale and microscale structures. The measured stationary and transient results of the fabricated photothermal transducers agreed well with the simulated results. From the input view, due to its wide spectrum and high absorption, the black coating with nanoscale structures contributed to a 5.6-fold increase in the temperature difference compared to that without the black coating. From the output view, the microgap structures in the Si layer eliminated the in-plane thermal crosstalk. The temperature difference was increased by 340% by modulating the out-of-plane microstructures. The proposed photothermal transducer had a rising time of 0.95 ms and a falling time of 0.53 ms, ensuring a fast time response. This method is compatible with low-cost and mass manufacturing and has promising potential to achieve ultralarge-array pixels beyond ten million.
Dopamine and fear memory formation in the human amygdala
Authors: Frick Andreas , Björkstrand Johannes , Lubberink Mark , Eriksson Allison , Fredrikson Mats , Åhs Fredrik
Published: December 2021

Learning which environmental cues that predict danger is crucial for survival and accomplished through Pavlovian fear conditioning. In humans and rodents alike, fear conditioning is amygdala-dependent and rests on similar neurocircuitry. Rodent studies have implicated a causative role for dopamine in the amygdala during fear memory formation, but the role of dopamine in aversive learning in humans is unclear. Here, we show dopamine release in the amygdala and striatum during fear learning in humans. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we demonstrate that the amount of dopamine release is linked to strength of conditioned fear responses and linearly coupled to learning-induced activity in the amygdala. Thus, like in rodents, formation of amygdala-dependent fear memories in humans seems to be facilitated by endogenous dopamine release, supporting an evolutionary conserved neurochemical mechanism for aversive memory formation.
LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells
Authors: Pu Youguang , Tan Yiao , Zang Chunbao , Zhao Fangfang , Cai Cifeng , Kong Lingsuo , Deng Hui , Chao Fengmei , Xia Ran , Xie Minghua , Ge Fangfang , Pan Yueyin , Cai Shanbao , Huang Dabing
Published: December 2021

Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.
Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop
Authors: Ding Yan , Wang Guiping , Zhan Meixiao , Sun Xiaohan , Deng Yanran , Zhao Yunhe , Liu Bin , Liu Qingxin , Wu Shian , Zhou Zizhang
Published: December 2021

Metastasis is an important cause of death from malignant tumors. It is of great significance to explore the molecular mechanism of metastasis for the development of anti-cancer drugs. Here, we find that the Hippo pathway hampers tumor cell metastasis in vivo. Silence of hpo or its downstream wts promotes tumor cell migration in a Yki-dependent manner. Furthermore, we identify that inhibition of the Hippo pathway promotes tumor cell migration through transcriptional activating src42A, a Drosophila homolog of the SRC oncogene. Yki activates src42A transcription through direct binding its intron region. Intriguingly, Src42A further increases Yki transcriptional activity to form a positive feedback loop. Finally, we show that SRC is also a target of YAP and important for YAP to promote the migration of human hepatocellular carcinoma cells. Together, our findings uncover a conserved Yki/YAP-Src42A/SRC positive feedback loop promoting tumor cell migration and provide SRC as a potential therapeutic target for YAP-driven metastatic tumors.
Modeling serological testing to inform relaxation of social distancing for COVID-19 control
Authors: Kraay Alicia N. M. , Nelson Kristin N. , Zhao Conan Y. , Demory David , Weitz Joshua S. , Lopman Benjamin A.
Published: December 2021

Serological testing remains a passive component of the public health response to the COVID-19 pandemic. Using a transmission model, we examine how serological testing could have enabled seropositive individuals to increase their relative levels of social interaction while offsetting transmission risks. We simulate widespread serological testing in New York City, South Florida, and Washington Puget Sound and assume seropositive individuals partially restore their social contacts. Compared to no intervention, our model suggests that widespread serological testing starting in late 2020 would have averted approximately 3300 deaths in New York City, 1400 deaths in South Florida and 11,000 deaths in Washington State by June 2021. In all sites, serological testing blunted subsequent waves of transmission. Findings demonstrate the potential benefit of widespread serological testing, had it been implemented in the pre-vaccine era, and remain relevant now amid the potential for emergence of new variants.
Individual differences in information-seeking
Authors: Kelly Christopher. A. , Sharot Tali
Published: December 2021

Vast amounts of personalized information are now available to individuals. A vital research challenge is to establish how people decide what information they wish to obtain. Here, over five studies examining information-seeking in different domains we show that information-seeking is associated with three diverse motives. Specifically, we find that participants assess whether information is useful in directing action, how it will make them feel, and whether it relates to concepts they think of often. We demonstrate that participants integrate these assessments into a calculation of the value of information that explains information seeking or its avoidance. Different individuals assign different weights to these three factors when seeking information. Using a longitudinal approach, we find that the relative weights assigned to these information-seeking motives within an individual show stability over time, and are related to mental health as assessed using a battery of psychopathology questionnaires.
Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers
Authors: Park Solip , Supek Fran , Lehner Ben
Published: December 2021

The classic two-hit model posits that both alleles of a tumor suppressor gene (TSG) must be inactivated to cause cancer. In contrast, for some oncogenes and haploinsufficient TSGs, a single genetic alteration can suffice to increase tumor fitness. Here, by quantifying the interactions between mutations and copy number alterations (CNAs) across 10,000 tumors, we show that many cancer genes actually switch between acting as one-hit or two-hit drivers. Third order genetic interactions identify the causes of some of these switches in dominance and dosage sensitivity as mutations in other genes in the same biological pathway. The correct genetic model for a gene thus depends on the other mutations in a genome, with a second hit in the same gene or an alteration in a different gene in the same pathway sometimes representing alternative evolutionary paths to cancer.
Water sources aggregate parasites with increasing effects in more arid conditions
Authors: Titcomb Georgia , Mantas John Naisikie , Hulke Jenna , Rodriguez Ivan , Branch Douglas , Young Hillary
Published: December 2021

Shifts in landscape heterogeneity and climate can influence animal movement in ways that profoundly alter disease transmission. Water sources that are foci of animal activity have great potential to promote disease transmission, but it is unknown how this varies across a range of hosts and climatic contexts. For fecal-oral parasites, water resources can aggregate many different hosts in small areas, concentrate infectious material, and function as disease hotspots. This may be exacerbated where water is scarce and for species requiring frequent water access. Working in an East African savanna, we show via experimental and observational methods that water sources increase the density of wild and domestic herbivore feces and thus, the concentration of fecal-oral parasites in the environment, by up to two orders of magnitude. We show that this effect is amplified in drier areas and drier periods, creating dynamic and heterogeneous disease landscapes across space and time. We also show that herbivore grazing behaviors that expose them to fecal-oral parasites often increase at water sources relative to background sites, increasing potential parasite transmission at these hotspots. Critically, this effect varies by herbivore species, with strongest effects for two animals of concern for conservation and development: elephants and cattle.
Time-restricted feeding induces Lactobacillus- and Akkermansia-specific functional changes in the rat fecal microbiota
Authors: Palomba Antonio , Tanca Alessandro , Abbondio Marcello , Sau Rosangela , Serra Monica , Marongiu Fabio , Fraumene Cristina , Pagnozzi Daniela , Laconi Ezio , Uzzau Sergio
Published: December 2021

Diet is a key factor influencing gut microbiota (GM) composition and functions, which in turn affect host health. Among dietary regimens, time-restricted (TR) feeding has been associated to numerous health benefits. The impact of TR feeding on the GM composition has been mostly explored by means of metagenomic sequencing. To date, however, little is known about the modulation of GM functions by this dietary regimen. Here, we analyzed the effects of TR feeding on GM functions by evaluating protein expression changes in a rat model through a metaproteomic approach. We observed that TR feeding has a relevant impact on GM functions, specifically leading to an increased abundance of several enzymes involved in carbohydrate and protein metabolism and expressed byLactobacillusspp. andAkkermansia muciniphila. Taken together, these results contribute to deepening our knowledge about the key relationship between diet, GM, and health.
Degenerate topological line surface phonons in quasi-1D double helix crystal SnIP
Authors: Peng Bo , Murakami Shuichi , Monserrat Bartomeu , Zhang Tiantian
Published: December 2021

Degenerate points/lines in the band structures of crystals have become a staple of the growing number of topological materials. The bulk-boundary correspondence provides a relation between bulk topology and surface states. While line degeneracies of bulk excitations have been extensively characterised, line degeneracies of surface states are not well understood. We show that SnIP, a quasi-one-dimensional van der Waals material with a double helix crystal structure, exhibits topological nodal rings/lines in both the bulk phonon modes and their corresponding surface states. Using a combination of first-principles calculations, symmetry-based indicator theories and Zak phase analysis, we find that two neighbouring bulk nodal rings form doubly degenerate lines in their drumhead-like surface states, which are protected by the combination of time-reversal symmetry $${{{\mathcal{T}}}}$$
T
and glide mirror symmetry $${\bar{M}}_{y}$$

M

¯

y

. Our results indicate that surface degeneracies can be generically protected by symmetries such as $${{{\mathcal{T}}}}{\bar{M}}_{y}$$

T

M

¯

y

, and phonons provide an ideal platform to explore such degeneracies.
Most myopathic lamin variants aggregate: a functional genomics approach for assessing variants of uncertain significance
Authors: Anderson Corey L. , Langer Emma R. , Routes Timothy C. , McWilliams Seamus F. , Bereslavskyy Igor , Kamp Timothy J. , Eckhardt Lee L.
Published: December 2021

Hundreds of LMNA variants have been associated with several distinct disease phenotypes. However, genotype–phenotype relationships remain largely undefined and the impact for most variants remains unknown. We performed a functional analysis for 178 variants across five structural domains using two different overexpression models. We found that lamin A aggregation is a major determinant for skeletal and cardiac laminopathies. An in vitro solubility assay shows that aggregation-prone variants in the immunoglobulin-like domain correlate with domain destabilization. Finally, we demonstrate that myopathic-associated LMNA variants show aggregation patterns in induced pluripotent stem cell derived-cardiomyocytes (iPSC-CMs) in contrast to non-myopathic LMNA variants. Our data-driven approach (1) reveals that striated muscle laminopathies are predominantly protein misfolding diseases, (2) demonstrates an iPSC-CM experimental platform for characterizing laminopathic variants in human cardiomyocytes, and (3) supports a functional assay to aid in assessing pathogenicity for myopathic variants of uncertain significance.
Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-β
Authors: Nickel Sandra , Vlaic Sebastian , Christ Madlen , Schubert Kristin , Henschler Reinhard , Tautenhahn Franziska , Burger Caroline , Kühne Hagen , Erler Silvio , Roth Andreas , Wild Christiane , Brach Janine , Hammad Seddik , Gittel Claudia , Baunack Manja , Lange Undine , Broschewitz Johannes , Stock Peggy , Metelmann Isabella , Bartels Michael , Pietsch Uta-Carolin , Krämer Sebastian , Eichfeld Uwe , von Bergen Martin , Dooley Steven , Tautenhahn Hans-Michael , Christ Bruno
Published: December 2021

Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-β (TGF-β) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-β, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-β signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-β.
Water sources and kidney function: investigating chronic kidney disease of unknown etiology in a prospective study
Authors: Vlahos Penny , Schensul Stephen L. , Anand Shuchi , Shipley Emma , Diyabalanage Saranga , Hu Chaoran , Ha Toan , Staniec Allison , Haider Lalarukh , Schensul Jean J. , Hewavitharane Pasan , Silva Tudor , Chandrajith Rohana , Nanayakkara Nishantha
Published: December 2021

A chronic Kidney Disease of unknown etiology (CKDu) has emerged with disproportionately high prevalence across dry lowland agricultural communities globally. Here we present the results of a prospective cohort of 293 patients with CKDu in the endemic region of Wilgamuwa, Sri Lanka, in whom we measured baseline kidney function and undertook quarterly follow up over 2 years. Well water was the primary historic drinking water source in the region, although a majority (68%) of participants reported switching to reverse osmosis water during study follow ups. Participants who reported ever drinking from well water had estimated glomerular filtration rates −6.7 (SD: 2.8) ml/min/1.73 m2 lower than participants who did not drink from well water historically (p = 0.0184) during the study period. Geospatial analysis identifies a cluster within the region where CKDu progression is significantly higher than the surrounding area. Samples of household wells (n = 262) indicated 68% had detectable agrochemical compounds with concentration above global water quality standards. It is expected that the detected contaminants compounds are indicators of poor water quality and that there is likely additional agrochemical exposure including commercial additives that may contribute to CKDu onset and/or progression. Thus, our study finds that well water exposure during a person’s lifetime in this region is associated with kidney function decline and identifies and quantifies putative nephrotoxic agrochemicals above safe drinking water concentrations in these wells.
Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis
Authors: Haytural Hazal , Benfeitas Rui , Schedin-Weiss Sophia , Bereczki Erika , Rezeli Melinda , Unwin Richard D. , Wang Xusheng , Dammer Eric B. , Johnson Erik C. B. , Seyfried Nicholas T. , Winblad Bengt , Tijms Betty M. , Visser Pieter Jelle , Frykman Susanne , Tjernberg Lars O.
Published: December 2021

Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.
ProMetIS, deep phenotyping of mouse models by combined proteomics and metabolomics analysis
Authors: Imbert Alyssa , Rompais Magali , Selloum Mohammed , Castelli Florence , Mouton-Barbosa Emmanuelle , Brandolini-Bunlon Marion , Chu-Van Emeline , Joly Charlotte , Hirschler Aurélie , Roger Pierrick , Burger Thomas , Leblanc Sophie , Sorg Tania , Ouzia Sadia , Vandenbrouck Yves , Médigue Claudine , Junot Christophe , Ferro Myriam , Pujos-Guillot Estelle , de Peredo Anne Gonzalez , Fenaille François , Carapito Christine , Herault Yann , Thévenot Etienne A.
Published: December 2021

Genes are pleiotropic and getting a better knowledge of their function requires a comprehensive characterization of their mutants. Here, we generated multi-level data combining phenomic, proteomic and metabolomic acquisitions from plasma and liver tissues of two C57BL/6 N mouse models lacking the Lat (linker for activation of T cells) and the Mx2 (MX dynamin-like GTPase 2) genes, respectively. Our dataset consists of 9 assays (1 preclinical, 2 proteomics and 6 metabolomics) generated with a fully non-targeted and standardized approach. The data and processing code are publicly available in the ProMetIS R package to ensure accessibility, interoperability, and reusability. The dataset thus provides unique molecular information about the physiological role of the Lat and Mx2 genes. Furthermore, the protocols described herein can be easily extended to a larger number of individuals and tissues. Finally, this resource will be of great interest to develop new bioinformatic and biostatistic methods for multi-omics data integration.
Meteorological and social conditions contribute to infectious diarrhea in China
Authors: Yang Xiang , Xiong Weifeng , Huang Tianyao , He Juan
Published: December 2021

Infectious diarrhea in China showed a significant pattern. Many researchers have tried to reveal the drivers, yet usually only meteorological factors were taken into consideration. Furthermore, the diarrheal data they analyzed were incomplete and the algorithms they exploited were inefficient of adapting realistic relationships. Here, we investigate the impacts of meteorological and social factors on the number of infectious diarrhea cases in China. A machine learning algorithm called the Random Forest is utilized. Our results demonstrate that nearly half of infectious diarrhea occurred among children under 5 years old. Generally speaking, increasing temperature or relative humidity leads to increased cases of infectious diarrhea in China. Nevertheless, people from different age groups or different regions own different sensitivities to meteorological factors. The weight of feces that are harmfully treated could be a possible reason for infectious diarrhea of the elderly as well as children under 5 years old. These findings indicate that infectious diarrhea prevention for children under 5 years old remains a primary task in China. Personalized prevention countermeasures ought to be provided to different age groups and different regions. It is essential to bring the weight of feces that are harmfully treated to the forefront when considering infectious diarrhea prevention.
Local delivery of hydrogel encapsulated vascular endothelial growth factor for the prevention of medication-related osteonecrosis of the jaw
Authors: Sharma Dileep , Hamlet Stephen , Vaquette Cedryck , Petcu Eugen Bogdan , Ramamurthy Poornima , Ivanovski Saso
Published: December 2021

The anti-angiogenic effects of bisphosphonates have been hypothesized as one of the major etiologic factors in the development of medication-related osteonecrosis of the jaw (MRONJ), a severe debilitating condition with limited treatment options. This study evaluated the potential of a gelatine-hyaluronic acid hydrogel loaded with the angiogenic growth factor, vascular endothelial growth factor (VEGF), as a local delivery system to aid in maintaining vascularization in a bisphosphonate-treated (Zoledronic Acid) rodent maxillary extraction defect. Healing was assessed four weeks after implantation of the VEGF-hydrogel into extraction sockets. Gross examination and histological assessment showed that total osteonecrosis and inflammatory infiltrate was significantly reduced in the presence of VEGF. Also, total vascularity and specifically neovascularization, was significantly improved in animals that received VEGF hydrogel. Gene expression of vascular, inflammatory and bone specific markers within the defect area were also significantly altered in the presence of VEGF. Furthermore, plasma cytokine levels were assessed to determine the systemic effect of locally delivered VEGF and showed similar outcomes. In conclusion, the use of locally delivered VEGF within healing extraction sockets assists bone healing and prevents MRONJ via a pro-angiogenic and immunomodulatory mechanism.
Identification of climate induced optimal rice yield and vulnerable districts rankings of the Punjab, Pakistan
Authors: Janjua Azhar Ali , Aslam Muhammad , Sultana Naheed , Batool Zia
Published: December 2021

The study attracted to insinuate the inhabitant anomalies of the crop yield in the districts of the Punjab where climate variation, inputs utilization, and district exponents are indispensable factors. Impact evaluation of sowing and harvesting dates for rice yield has been analyzed. Suitable sowing and harvesting dates and potential districts for the crop are proposed. Data consisting of 13,617 observations of more than 90 factors encompassing valuable dimensions of the growth of the crops collected through comprehensive surveys conducted by the Agriculture Department of Punjab are formulated to incorporate in this study. The results establish the significant negative repercussions of climate variability while the impacts vary in the districts. The crop yield deteriorates considerably by delaying the sowing and harvesting times. Districts climate-induced vulnerability ranking revealed Layyah, Jhelum, Mianwali, Khanewal and Chinniot, the most vulnerable while Kasur, Gujrat, Mandi Bhauddin, Nankana Sahib and Hafizabad, the least vulnerable districts. Spatial mapping explains the geographical pattern of vulnerabilities and yield/monetary losses. The study ranks districts using climate-induced yield and monetary loss (222.30 thousand metric tons of rice which are equal to 27.79 billion PKR climatic losses in single rice season) and recommends: the formation of district policy to abate the adverse climate impact, utilization of suitable climate variation by adhering proper sowing and harvesting times, setting the prioritized districts facing climate-induced losses for urgent attention and preferable districts for rice crop.