bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-specific risk profiles for suicide mortality in bipolar disorder: incidence, healthcare utilization and comorbidity
Authors: Chen Pao-Huan , Tsai Shang-Ying , Pan Chun-Hung , Chen Yi-Lung , Chang Hu-Ming , Su Sheng-Siang , Chen Chiao-Chicy , Kuo Chian-Jue
Published: August 2021

Background

Evidence on sex-specific incidence and comorbidity risk factors of suicide among patients with bipolar disorder is scarce. This study investigated the sex-specific risk profiles for suicide among the bipolar disorder population in terms of incidence, healthcare utilization and comorbidity.

Methods

Using data from the Taiwan National Health Insurance Research Database between 1 January 2000 and 31 December 2016, this nationwide cohort study included patients with bipolar disorder (N = 46 490) and individuals representative of the general population (N = 185 960) matched by age and sex at a 1:4 ratio. Mortality rate ratios (MRRs) of suicide were calculated between suicide rates of bipolar disorder cohort and general population. In addition, a nested case–control study (1428 cases died by suicide and 5710 living controls) was conducted in the bipolar disorder cohort to examine the sex-specific risk of healthcare utilization and comorbidities.

Results

Suicide risk was considerably higher in the cohort (MRR = 21.9) than in the general population, especially among women (MRR = 35.6). Sex-stratified analyses revealed distinct healthcare utilization patterns and physical comorbidity risk profiles between the sexes. Although female patients who died by suicide had higher risks of nonhypertensive cardiovascular disease, pneumonia, chronic kidney disease, peptic ulcer, irritable bowel syndrome, and sepsis compared to their living counterparts, male patients who died by suicide had higher risks of chronic kidney disease and sepsis compared to the living controls.

Conclusions

Patients with bipolar disorder who died by suicide had sex-specific risk profiles in incidence and physical comorbidities. Identifying these modifiable risk factors may guide interventions for suicide risk reduction.
Linguistic constraint, social meaning, and multi-modal stylistic construction: Case studies from Mandarin pop songs
Authors: Lin Yuhan , Chan Marjorie K. M.
Published: August 2021

While the sociolinguistic variable is often deemed the carrier of social meaning, recent work reveals that the strength of social meaning can interact with linguistic environments. This study provides additional evidence that the same sets of variants can index drastically different social meanings across linguistic environments. Specifically, we present two cases of linguistic stylization in Taiwanese singer Jay Chou's performance in different genres: the ‘Chinese Flavor’ ballad and hip hop. Focusing on two socially salient variables in Mandarin—rhotacization and retroflex sibilants—we argue that while in both cases, Chou adopts variants associated with standard and mainland Mandarin, they index different social meanings. The conforming linguistic use in the ‘Chinese Flavor’ ballad indexes a sense of tradition, whereas the hypercorrected forms in the hip-hop song construct an unconventional stance. The study also addresses the connections between linguistic and non-linguistic stylizations and calls for more research on the multimodal construction of style. (Social meaning, linguistic constraint, multimodal, high performance, Mandarin)*
The prevalence of diagnosed specific back pain in primary health care in Region Västra Götaland: a register study of 1.7 million inhabitants
Authors: Kruse Madeleine , Thoreson Olof
Published: August 2021

Objectives:

To evaluate the one-year prevalence of diagnosed specific back pain in Region Västra Götaland, inhabiting 1.7 million people.

Designs:

A retrospective register study.

Settings:

Data from 2014 to 2019 were extracted from the VEGA register, which holds all health data from all publicly funded health care establishments in Region Västra Götaland. Aggregated data are presented as the one-year prevalence of unique individuals diagnosed with International Statistical Classification of Diseases and Related Health Problems – Tenth Revision codes representing specific back pain.

Subjects:

All inhabitants in Region Västra Götaland.

Main outcome measures:

The one-year prevalence of diagnosed specific back pain stratified by age, sex, and health care level.

Results:

In 2019, the one-year prevalence of diagnosed specific back pain in public primary health care centres was 0.82%, rehabilitation care 0.35%, and the combined increase was 156% from 2014. In specialized health care, the diagnosed prevalence during 2014–2019 has remained relatively unchanged. The prevalence was significantly higher among women in primary health care and rehabilitation care. M48.0 (spinal stenosis) and M51.1K (lumbar disc herniation with radiculopathy) were the most common sub-classifications. For M48.0, prevalence increased by age, whereas M51.1K peaked within the 45–64 years category.

Conclusions:

The one-year prevalence of diagnosed specific back pain in primary health care was 1.17% in 2019 and has increased since 2014. Women were diagnosed considerably more frequently than men, which is not reflected in surgical treatment prevalence.
SIMPLICIUS ON THE FILLING OF SPACE, IN CAELO 655.9–656.5: A DELIBERATE MISTAKE?
Authors: Lloyd D. R.
Published: August 2021

In In cael. 655.9–656.5 Simplicius reports an argument in which an apparent justification is offered for the false claim by Aristotle that ‘pyramids’ (regular tetrahedra) can completely fill space. This argument was analysed by Ian Mueller in an Appendix to his translation of In caelo, and the outline of an alternative has been presented in Myrto Hatzimichali's study of Potamo of Alexandria. In this article I contest Mueller's interpretation, and expand on the one reported by Hatzimichali. I also contest Mueller's claim that a version of his interpretation can be found in the partial commentary by Peter of Auvergne. It is suggested here that the ‘justification’ reported by Simplicius is a deliberate slip in logic, which is accompanied by a carefully constructed cover-up involving some quite tricky geometry. Simplicius makes frequent reference to Alexander of Aphrodisias, but it is argued here that he has been very selective with these citations.
Violence and repair: The practice and challenges of non-State armed groups engaging in reparations
Authors: Moffett Luke
Published: August 2021

Atrocities by non-State armed groups (NSAGs) often capture international attention, but efforts to repair the harm they have caused are often overlooked. This article traces out some of the practices and tensions in NSAGs making reparations during wartime and in post-conflict transitions. It argues that engaging in reparations for acts committed by NSAGs can not only encourage greater compliance with international humanitarian law but also build support amongst civilian populations during armed conflict and facilitate ex-fighter reintegration at the end of hostilities. Drawing from interviews with a number of armed groups, the article also suggests that engaging with the armed group's organization rather than just individuals themselves can be an effective way to collectively mobilize a group's motivation and capacity to deliver on reparations, including recovery of disappeared persons, restitution of property and apologies. As such, this article seeks to contribute to a deeper understanding of reparation practices by NSAGs in order to see how reparations can be mediated and a hierarchy of reparation obligations developed.
Fighting Deforestation in Non-International Armed Conflicts: The Relevance of the Rome Statute for Rosewood Trafficking in Senegal
Authors: Martini Pauline , Sarliève Maud
Published: August 2021

This article examines rosewood trafficking in the Casamance region of Senegal to determine whether acts of massive deforestation committed in the context of a non-international armed conflict can be prosecuted before the International Criminal Court (ICC) as war crimes of pillage and destruction of property under Article 8(2)(e)(v) and (xii) of the Rome Statute, respectively. It examines two of the main challenges resulting from the application of these provisions to acts of massive deforestation in the light of the ICC Elements of Crimes. Firstly, the article addresses the delicate issue of the establishment of a nexus between these acts and the related non-international armed conflict. Secondly, it discusses whether natural resources may qualify as ‘property’ for the purpose of Article 8(2)(e)(v) and (xii). It then offers avenues of reflection regarding the determination of ownership of these resources to fulfil the requirements of the Rome Statute.
Exploring Negative Beliefs About Power
Authors: Wingen Tobias , Dohle Simone
Published: August 2021

Abstract. “The powerful are immoral”! Across four preregistered studies (total N = 2,744), we explored the role of perceived autonomy (control over own resources) and perceived influence (control over others’ resources) for this belief. In Study 1, perceived autonomy and influence mediated the effect of power on expected immorality. Likewise, directly manipulating perceived autonomy and influence led to increased expected immorality, increased perceived intentionality of a transgression, and consequently to harsher punishment recommendations (Studies 3 and 4). Interestingly, Study 2 revealed an interaction between autonomy and influence, which we however could not replicate in Study 4. Overall, our findings suggest that both autonomy and influence are associated with immorality and thus likely drive the belief that the powerful are immoral.
Perceptions of Just Culture Between Pilots and	Managers
Authors: Schuit Inge , Scott Steve
Published: August 2021

Abstract. Airline safety can be improved when errors and incidents by aircrew are openly reported and justly investigated. Trust and functioning of the reporting system are critical for the success of a just safety culture. In this study, interviews and surveys were used to investigate the similarities and/or differences in perceptions of pilots and managers within several airlines about perceived just culture. Results indicate that decisions about culpability, the line between acceptable an unacceptable behavior, and the result of introducing more consequences are perceived differently by pilots and managers.
The Plasma Environment Surrounding the Reiner Gamma Magnetic Anomaly
Authors: Deca J. , Poppe A. R. , Divin A. , Lembège B.
Published: August 2021

Reiner Gamma is a prime target for low‐orbiting spacecraft or even surface‐landed missions in the near future. The region hosts a prominent lunar swirl that is co‐located with a strong and well‐structured magnetic anomaly. We simulate and discuss Reiner Gamma's near‐surface plasma environment at different altitudes above the lunar surface using the fully kinetic particle‐in‐cell code iPIC3D. The input magnetic field model is based on orbital‐altitude observations from the Kaguya and Lunar Prospector missions. We develop eight simulation cases, representing the distinct plasma regimes. Reiner Gamma is exposed to along a typical orbit, including different solar wind incidence angles and the magnetosheath crossing. We show that the plasma environment is vastly different at different altitudes and depends critically on the upstream plasma parameters, consistent with the predictions of the solar wind standoff model. Our work helps to define measurement requirements for a possible future low‐orbiting or lander mission to the Reiner Gamma area or similarly magnetized regions of the lunar surface.
The Role of Flare‐Driven Ionospheric Electron Density Changes on the Doppler Flash Observed by SuperDARN HF Radars
Authors: Chakraborty S. , Qian L. , Ruohoniemi J. M. , Baker J. B. H. , Mclnerney J. M. , Nishitani N.
Published: August 2021

Trans‐ionospheric high frequency (HF: 3–30 MHz) signals experience strong attenuation following a solar flare‐driven sudden ionospheric disturbance (SID). Solar flare‐driven HF absorption, referred to as short‐wave fadeout, is a well‐known impact of SIDs, but the initial Doppler frequency shift phenomena, also known as “Doppler flash” in the traveling radio wave is not well understood. This study seeks to advance our understanding of the initial impacts of solar flare‐driven SID using a physics‐based whole atmosphere model for a specific solar flare event. First, we demonstrate that the Doppler flash phenomenon observed by Super Dual Auroral Radar Network (SuperDARN) radars can be successfully reproduced using first‐principles based modeling. The output from the simulation is validated against SuperDARN line‐of‐sight Doppler velocity measurements. We then examine which region of the ionosphere, D, E, or F, makes the largest contribution to the Doppler flash. We also consider the relative contribution of change in refractive index through the ionospheric layers versus lowered reflection height. We find: (a) the model is able to reproduce radar observations with an root‐median‐squared‐error and a mean percentage error (δ) of 3.72 m/s and 0.67%, respectively; (b) the F‐region is the most significant contributor to the total Doppler flash (∼48%), 30% of which is contributed by the change in F‐region's refractive index, while the other ∼18% is due to change in ray reflection height. Our analysis shows lowering of the F‐region's ray reflection point is a secondary driver compared to the change in refractive index.
Oxidation of Proteinaceous Matter by Ozone and Nitrogen Dioxide in PM2.5: Reaction Mechanisms and Atmospheric Implications
Authors: Zhu Ren‐Guo , Xiao Hua‐Yun , Wen Zequn , Zhu Yuwen , Fang Xiaozheng , Pan Yuanyuan , Chen Zhenping , Xiao Hongwei
Published: August 2021

Interactions between proteinaceous matter and atmospheric oxidants can affect amino acids (AAs) bioavailability, the climate, and human health. However, atmospheric reactions of proteinaceous matter remain poorly understood. PM2.5 samples were collected during spring (2019) and winter (2020) sampling campaigns conducted in Nanchang, China. Concentrations of combined and free AAs, and the δ15N values of combined and free glycine (C‐Gly and F‐Gly) in PM2.5 samples were analyzed. Concentrations of TFAA under different O3 and NO2 levels, and correlations of specific FAA species with ambient O3 and NO2 concentrations suggest that the ability of O3 to release TFAA from proteinaceous matter is greater than that of NO2. Furthermore, O3 may trend to release neutral and hydrophilic FAA species, whereas NO2 tends to generate hydrophobic FAA species. With aerosol aging, the slope of the fitted line between [TFAA] and [TSAA] [O3 + NO2] increased, indicating that FAAs yield from protein degradation in PM2.5 was affected greatly by aerosol aging. The TCAAs concentration observed in spring was substantially higher than that in winter. Moreover, the δ15NF‐Gly and δ15NC‐Gly values in PM2.5 exhibited negative correlations with atmospheric O3 concentration. These results suggest that increased levels of proteinaceous matter in spring were derived from natural sources related to biological activities rather than biomass burning sources. Our study confirms that the reaction of degradation of proteinaceous matter to FAAs could be influenced by aerosol aging, which is a finding that enhances current understanding regarding atmospheric processes of aerosol proteinaceous matter under different ambient O3 and NO2 levels.
Chemical Response of the Upper Atmosphere Due to Lightning‐Induced Electron Precipitation
Authors: Xu Wei , Marshall Robert A. , Kero Antti , Sousa Austin
Published: August 2021

Terrestrial lightning frequently serves as a loss mechanism for energetic electrons in the Van Allen radiation belts, leading to lightning‐induced electron precipitation (LEP). Regardless of the specific causes, energetic electron precipitation from the radiation belts in general has a significant influence on the ozone concentration in the stratosphere and mesosphere. The atmospheric chemical effects induced by LEP have been previously investigated using subionospheric VLF measurements at Faraday station, Antarctica (65.25°S, 64.27°W, L = 2.45). However, there exist large variations in the precipitation flux, ionization production, and occurrence rate of LEP events depending on the peak current of the parent lightning discharge, as well as the season, location, and intensity of the thunderstorm activity. These uncertainties motivate us to revisit the calculation of atmospheric chemical changes produced by LEP. In this study, we combine a well‐validated LEP model and first‐principles atmospheric chemical simulation, and investigate three intense storms in the year of 2013, 2015, and 2017 at the magnetic latitude of 50., 32., and 35., respectively. Modeling results show that the LEP events in these storms can cumulatively drive significant changes in the , , and concentration in the mesosphere. These changes are as high as , , and at 75–85 km altitude, respectively, and comparable to the effects typically induced by other types of radiation belt electron precipitation events. Considering the high occurrence rate of thunderstorms around the globe, the long‐term global chemical effects produced by LEP events need to be properly quantified.
Importance of Bcl-2-family proteins in murine hematopoietic progenitor and early B cells
Authors: Kurschat Constanze , Metz Arlena , Kirschnek Susanne , Häcker Georg
Published: August 2021

Mitochondrial apoptosis regulates survival and development of hematopoietic cells. Prominent roles of some Bcl-2-family members in this regulation have been established, for instance for pro-apoptotic Bim and anti-apoptotic Mcl-1. Additional, mostly smaller roles are known for other Bcl-2-members but it has been extremely difficult to obtain a comprehensive picture of the regulation of mitochondrial apoptosis in hematopoietic cells by Bcl-2-family proteins. We here use a system of mouse ‘conditionally immortalized’ lymphoid-primed hematopoietic progenitor (LMPP) cells that can be differentiated in vitro to pro-B cells, to analyze the importance of these proteins in cell survival. We established cells deficient in Bim, Noxa, Bim/Noxa, Bim/Puma, Bim/Bmf, Bax, Bak or Bax/Bak and use specific inhibitors of Bcl-2, Bcl-XL and Mcl-1 to assess their importance. In progenitor (LMPP) cells, we found an important role of Noxa, alone and together with Bim. Cell death induced by inhibition of Bcl-2 and Bcl-XL entirely depended on Bim and could be implemented by Bax and by Bak. Inhibition of Mcl-1 caused apoptosis that was independent of Bim but strongly depended on Noxa and was completely prevented by the absence of Bax; small amounts of anti-apoptotic proteins were co-immunoprecipitated with Bim. During differentiation to pro-B cells, substantial changes in the expression of Bcl-2-family proteins were seen, and Bcl-2, Bcl-XL and Mcl-1 were all partially in complexes with Bim. In differentiated cells, Noxa appeared to have lost all importance while the loss of Bim and Puma provided protection. The results strongly suggest that the main role of Bim in these hematopoietic cells is the neutralization of Mcl-1, identify a number of likely molecular events during the maintenance of survival and the induction of apoptosis in mouse hematopoietic progenitor cells, and provide data on the regulation of expression and importance of these proteins during differentiation along the B cell lineage.
Teaching a neural network to attach and detach electrons from molecules
Authors: Zubatyuk Roman , Smith Justin S. , Nebgen Benjamin T. , Tretiak Sergei , Isayev Olexandr
Published: August 2021

Interatomic potentials derived with Machine Learning algorithms such as Deep-Neural Networks (DNNs), achieve the accuracy of high-fidelity quantum mechanical (QM) methods in areas traditionally dominated by empirical force fields and allow performing massive simulations. Most DNN potentials were parametrized for neutral molecules or closed-shell ions due to architectural limitations. In this work, we propose an improved machine learning framework for simulating open-shell anions and cations. We introduce the AIMNet-NSE (Neural Spin Equilibration) architecture, which can predict molecular energies for an arbitrary combination of molecular charge and spin multiplicity with errors of about 2–3 kcal/mol and spin-charges with error errors ~0.01e for small and medium-sized organic molecules, compared to the reference QM simulations. The AIMNet-NSE model allows to fully bypass QM calculations and derive the ionization potential, electron affinity, and conceptual Density Functional Theory quantities like electronegativity, hardness, and condensed Fukui functions. We show that these descriptors, along with learned atomic representations, could be used to model chemical reactivity through an example of regioselectivity in electrophilic aromatic substitution reactions.
A last-in first-out stack data structure implemented in DNA
Authors: Lopiccolo Annunziata , Shirt-Ediss Ben , Torelli Emanuela , Olulana Abimbola Feyisara Adedeji , Castronovo Matteo , Fellermann Harold , Krasnogor Natalio
Published: August 2021

DNA-based memory systems are being reported with increasing frequency. However, dynamic DNA data structures able to store and recall information in an ordered way, and able to be interfaced with external nucleic acid computing circuits, have so far received little attention. Here we present an in vitro implementation of a stack data structure using DNA polymers. The stack is able to record combinations of two different DNA signals, release the signals into solution in reverse order, and then re-record. We explore the accuracy limits of the stack data structure through a stochastic rule-based model of the underlying polymerisation chemistry. We derive how the performance of the stack increases with the efficiency of washing steps between successive reaction stages, and report how stack performance depends on the history of stack operations under inefficient washing. Finally, we discuss refinements to improve molecular synchronisation and future open problems in implementing an autonomous chemical data structure.
Locomotion dependent neuron-glia interactions control neurogenesis and regeneration in the adult zebrafish spinal cord
Authors: Chang Weipang , Pedroni Andrea , Bertuzzi Maria , Kizil Caghan , Simon András , Ampatzis Konstantinos
Published: August 2021

Physical exercise stimulates adult neurogenesis, yet the underlying mechanisms remain poorly understood. A fundamental component of the innate neuroregenerative capacity of zebrafish is the proliferative and neurogenic ability of the neural stem/progenitor cells. Here, we show that in the intact spinal cord, this plasticity response can be activated by physical exercise by demonstrating that the cholinergic neurotransmission from spinal locomotor neurons activates spinal neural stem/progenitor cells, leading to neurogenesis in the adult zebrafish. We also show that GABA acts in a non-synaptic fashion to maintain neural stem/progenitor cell quiescence in the spinal cord and that training-induced activation of neurogenesis requires a reduction of GABAA receptors. Furthermore, both pharmacological stimulation of cholinergic receptors, as well as interference with GABAergic signaling, promote functional recovery after spinal cord injury. Our findings provide a model for locomotor networks’ activity-dependent neurogenesis during homeostasis and regeneration in the adult zebrafish spinal cord.
Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase
Authors: Newman Joseph A. , Douangamath Alice , Yadzani Setayesh , Yosaatmadja Yuliana , Aimon Antony , Brandão-Neto José , Dunnett Louise , Gorrie-stone Tyler , Skyner Rachael , Fearon Daren , Schapira Matthieu , von Delft Frank , Gileadi Opher
Published: August 2021

There is currently a lack of effective drugs to treat people infected with SARS-CoV-2, the cause of the global COVID-19 pandemic. The SARS-CoV-2 Non-structural protein 13 (NSP13) has been identified as a target for anti-virals due to its high sequence conservation and essential role in viral replication. Structural analysis reveals two “druggable” pockets on NSP13 that are among the most conserved sites in the entire SARS-CoV-2 proteome. Here we present crystal structures of SARS-CoV-2 NSP13 solved in the APO form and in the presence of both phosphate and a non-hydrolysable ATP analog. Comparisons of these structures reveal details of conformational changes that provide insights into the helicase mechanism and possible modes of inhibition. To identify starting points for drug development we have performed a crystallographic fragment screen against NSP13. The screen reveals 65 fragment hits across 52 datasets opening the way to structure guided development of novel antiviral agents.
ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer
Authors: Taftaf Rokana , Liu Xia , Singh Salendra , Jia Yuzhi , Dashzeveg Nurmaa K. , Hoffmann Andrew D. , El-Shennawy Lamiaa , Ramos Erika K. , Adorno-Cruz Valery , Schuster Emma J. , Scholten David , Patel Dhwani , Zhang Youbin , Davis Andrew A. , Reduzzi Carolina , Cao Yue , D’Amico Paolo , Shen Yang , Cristofanilli Massimo , Muller William A. , Varadan Vinay , Liu Huiping
Published: August 2021

Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency and are associated with lower overall survival in breast cancer compared to single cells. Combining single-cell RNA sequencing and protein analyses, here we report the profiles of primary tumor cells and lung metastases of triple-negative breast cancer (TNBC). ICAM1 expression increases by 200-fold in the lung metastases of three TNBC patient-derived xenografts (PDXs). Depletion of ICAM1 abrogates lung colonization of TNBC cells by inhibiting homotypic tumor cell-tumor cell cluster formation. Machine learning-based algorithms and mutagenesis analyses identify ICAM1 regions responsible for homophilic ICAM1-ICAM1 interactions, thereby directing homotypic tumor cell clustering, as well as heterotypic tumor-endothelial adhesion for trans-endothelial migration. Moreover, ICAM1 promotes metastasis by activating cellular pathways related to cell cycle and stemness. Finally, blocking ICAM1 interactions significantly inhibits CTC cluster formation, tumor cell transendothelial migration, and lung metastasis. Therefore, ICAM1 can serve as a novel therapeutic target for metastasis initiation of TNBC.
Genetic and environmental factors in Alzheimer’s and Parkinson’s diseases and promising therapeutic intervention via fecal microbiota transplantation
Authors: Wang Hui , Yang Feng , Zhang Shidong , Xin Ruihua , Sun Yan
Published: August 2021

Neurodegenerative diseases are characterized by neuronal impairment and loss of function, and with the major shared histopathological hallmarks of misfolding and aggregation of specific proteins inside or outside cells. Some genetic and environmental factors contribute to the promotion of the development and progression of neurodegenerative diseases. Currently, there are no effective treatments for neurodegenerative diseases. It has been revealed that bidirectional communication exists between the brain and the gut. The gut microbiota is a changeable and experience-dependent ecosystem and can be modified by genetic and environmental factors. The gut microbiota provides potential therapeutic targets that can be regulated as new interventions for neurodegenerative diseases. In this review, we discuss genetic and environmental risk factors for neurodegenerative diseases, summarize the communication among the components of the microbiota-gut-brain axis, and discuss the treatment strategy of fecal microbiota transplantation (FMT). FMT is a promising treatment for neurodegenerative diseases, and restoration of the gut microbiota to a premorbid state is a novel goal for prevention and treatment strategies.
Defining the variety of cell types in developing and adult human kidneys by single-cell RNA sequencing
Authors: Schumacher A. , Rookmaaker M. B. , Joles J. A. , Kramann R. , Nguyen T. Q. , van Griensven M. , LaPointe V. L. S.
Published: August 2021

The kidney is among the most complex organs in terms of the variety of cell types. The cellular complexity of human kidneys is not fully unraveled and this challenge is further complicated by the existence of multiple progenitor pools and differentiation pathways. Researchers disagree on the variety of renal cell types due to a lack of research providing a comprehensive picture and the challenge to translate findings between species. To find an answer to the number of human renal cell types, we discuss research that used single-cell RNA sequencing on developing and adult human kidney tissue and compares these findings to the literature of the pre-single-cell RNA sequencing era. We find that these publications show major steps towards the discovery of novel cell types and intermediate cell stages as well as complex molecular signatures and lineage pathways throughout development. The variety of cell types remains variable in the single-cell literature, which is due to the limitations of the technique. Nevertheless, our analysis approaches an accumulated number of 41 identified cell populations of renal lineage and 32 of non-renal lineage in the adult kidney, and there is certainly much more to discover. There is still a need for a consensus on a variety of definitions and standards in single-cell RNA sequencing research, such as the definition of what is a cell type. Nevertheless, this early-stage research already proves to be of significant impact for both clinical and regenerative medicine, and shows potential to enhance the generation of sophisticated in vitro kidney tissue.
A merged microarray meta-dataset for transcriptionally profiling colorectal neoplasm formation and progression
Authors: Rohr Michael , Beardsley Jordan , Nakkina Sai Preethi , Zhu Xiang , Aljabban Jihad , Hadley Dexter , Altomare Deborah
Published: August 2021

Transcriptional profiling of pre- and post-malignant colorectal cancer (CRC) lesions enable temporal monitoring of molecular events underlying neoplastic progression. However, the most widely used transcriptomic dataset for CRC, TCGA-COAD, is devoid of adenoma samples, which increases reliance on an assortment of disparate microarray studies and hinders consensus building. To address this, we developed a microarray meta-dataset comprising 231 healthy, 132 adenoma, and 342 CRC tissue samples from twelve independent studies. Utilizing a stringent analytic framework, select datasets were downloaded from the Gene Expression Omnibus, normalized by frozen robust multiarray averaging and subsequently merged. Batch effects were then identified and removed by empirical Bayes estimation (ComBat). Finally, the meta-dataset was filtered for low variant probes, enabling downstream differential expression as well as quantitative and functional validation through cross-platform correlation and enrichment analyses, respectively. Overall, our meta-dataset provides a robust tool for investigating colorectal adenoma formation and malignant transformation at the transcriptional level with a pipeline that is modular and readily adaptable for similar analyses in other cancer types.
A near-global, high resolution land surface parameter dataset for the variable infiltration capacity model
Authors: Schaperow Jacob R. , Li Dongyue , Margulis Steven A. , Lettenmaier Dennis P.
Published: August 2021

Hydrologic models predict the spatial and temporal distribution of water and energy at the land surface. Currently, parameter availability limits global-scale hydrologic modelling to very coarse resolution, hindering researchers from resolving fine-scale variability. With the aim of addressing this problem, we present a set of globally consistent soil and vegetation parameters for the Variable Infiltration Capacity (VIC) model at 1/16° resolution (approximately 6 km at the equator), with spatial coverage from 60°S to 85°N. Soil parameters derived from interpolated soil profiles and vegetation parameters estimated from space-based MODIS measurements have been compiled into input files for both the Classic and Image drivers of the VIC model, version 5. Geographical subsetting codes are provided, as well. Our dataset provides all necessary land surface parameters to run the VIC model at regional to global scale. We evaluate VICGlobal’s ability to simulate the water balance in the Upper Colorado River basin and 12 smaller basins in the CONUS, and their ability to simulate the radiation budget at six SURFRAD stations in the CONUS.
Effects of interobserver and interdisciplinary segmentation variabilities on CT-based radiomics for pancreatic cancer
Authors: Wong Jeffrey , Baine Michael , Wisnoskie Sarah , Bennion Nathan , Zheng Dechun , Yu Lei , Dalal Vipin , Hollingsworth Michael A. , Lin Chi , Zheng Dandan
Published: August 2021

Radiomics is a method to mine large numbers of quantitative imaging features and develop predictive models. It has shown exciting promise for improved cancer decision support from early detection to personalized precision treatment, and therefore offers a desirable new direction for pancreatic cancer where the mortality remains high despite the current care and intense research. For radiomics, interobserver segmentation variability and its effect on radiomic feature stability is a crucial consideration. While investigations have been reported for high-contrast cancer sites such as lung cancer, no studies to date have investigated it on CT-based radiomics for pancreatic cancer. With three radiation oncology observers and three radiology observers independently contouring on the contrast CT of 21 pancreatic cancer patients, we conducted the first interobserver segmentation variability study on CT-based radiomics for pancreatic cancer. Moreover, our novel investigation assessed whether there exists an interdisciplinary difference between the two disciplines. For each patient, a consensus tumor volume was generated using the simultaneous truth and performance level expectation algorithm, using the dice similarity coefficient (DSC) to assess each observer’s delineation against the consensus volume. Radiation oncology observers showed a higher average DSC of 0.81 ± 0.06 than the radiology observers at 0.69 ± 0.16 (p = 0.002). On a panel of 1277 radiomic features, the intraclass correlation coefficients (ICC) was calculated for all observers and those of each discipline. Large variations of ICCs were observed for different radiomic features, but ICCs were generally higher for the radiation oncology group than for the radiology group. Applying a threshold of ICC > 0.75 for considering a feature as stable, 448 features (35%) were found stable for the radiation oncology group and 214 features (16%) were stable from the radiology group. Among them, 205 features were found stable for both groups. Our results provide information for interobserver segmentation variability and its effect on CT-based radiomics for pancreatic cancer. An interesting interdisciplinary variability found in this study also introduces new considerations for the deployment of radiomics models.
Diffusible signal factor signaling controls bioleaching activity and niche protection in the acidophilic, mineral-oxidizing leptospirilli
Authors: Bellenberg Sören , Salas Beatriz , Ganji Suresh , Jorquera-Román Cristian , Valenzuela Maria Luisa , Buetti-Dinh Antoine , Unelius C. Rikard , Dopson Mark , Vera Mario
Published: August 2021

Bioleaching of metal sulfide ores involves acidophilic microbes that catalyze the chemical dissolution of the metal sulfide bond that is enhanced by attached and planktonic cell mediated oxidation of iron(II)-ions and inorganic sulfur compounds. Leptospirillum spp. often predominate in sulfide mineral-containing environments, including bioheaps for copper recovery from chalcopyrite, as they are effective primary mineral colonizers and oxidize iron(II)-ions efficiently. In this study, we demonstrated a functional diffusible signal factor interspecies quorum sensing signaling mechanism in Leptospirillum ferriphilum and Leptospirillum ferrooxidans that produces (Z)-11-methyl-2-dodecenoic acid when grown with pyrite as energy source. In addition, pure diffusible signal factor and extracts from supernatants of pyrite grown Leptospirillum spp. inhibited biological iron oxidation in various species, and that pyrite grown Leptospirillum cells were less affected than iron grown cells to self inhibition. Finally, transcriptional analyses for the inhibition of iron-grown L. ferriphilum cells due to diffusible signal factor was compared with the response to exposure of cells to N- acyl-homoserine-lactone type quorum sensing signal compounds. The data suggested that Leptospirillum spp. diffusible signal factor production is a strategy for niche protection and defense against other microbes and it is proposed that this may be exploited to inhibit unwanted acidophile species.
A differential equations model-fitting analysis of COVID-19 epidemiological data to explain multi-wave dynamics
Authors: Beira Maria Jardim , Sebastião Pedro José
Published: August 2021

Compartmental epidemiological models are, by far, the most popular in the study of dynamics related with infectious diseases. It is, therefore, not surprising that they are frequently used to study the current COVID-19 pandemic. Taking advantage of the real-time availability of COVID-19 related data, we perform a compartmental model fitting analysis of the portuguese case, using an online open-access platform with the integrated capability of solving systems of differential equations. This analysis enabled the data-driven validation of the used model and was the basis for robust projections of different future scenarios, namely, increasing the detected infected population, reopening schools at different moments, allowing Easter celebrations to take place and population vaccination. The method presented in this work can easily be used to perform the non-trivial task of simultaneously fitting differential equation solutions to different epidemiological data sets, regardless of the model or country that might be considered in the analysis.
Hyperglycaemia up-regulates placental growth factor (PlGF) expression and secretion in endothelial cells via suppression of PI3 kinase-Akt signalling and activation of FOXO1
Authors: Sissaoui Samir , Egginton Stuart , Ting Ling , Ahmed Asif , Hewett Peter W.
Published: August 2021

Placenta growth factor (PlGF) is a pro-inflammatory angiogenic mediator that promotes many pathologies including diabetic complications and atherosclerosis. Widespread endothelial dysfunction precedes the onset of these conditions. As very little is known of the mechanism(s) controlling PlGF expression in pathology we investigated the role of hyperglycaemia in the regulation of PlGF production in endothelial cells. Hyperglycaemia stimulated PlGF secretion in cultured primary endothelial cells, which was suppressed by IGF-1-mediated PI3K/Akt activation. Inhibition of PI3K activity resulted in significant PlGF mRNA up-regulation and protein secretion. Similarly, loss or inhibition of Akt activity significantly increased basal PlGF expression and prevented any further PlGF secretion in hyperglycaemia. Conversely, constitutive Akt activation blocked PlGF secretion irrespective of upstream PI3K activity demonstrating that Akt is a central regulator of PlGF expression. Knock-down of the Forkhead box O-1 (FOXO1) transcription factor, which is negatively regulated by Akt, suppressed both basal and hyperglycaemia-induced PlGF secretion, whilst FOXO1 gain-of-function up-regulated PlGF in vitro and in vivo. FOXO1 association to a FOXO binding sequence identified in the PlGF promoter also increased in hyperglycaemia. This study identifies the PI3K/Akt/FOXO1 signalling axis as a key regulator of PlGF expression and unifying pathway by which PlGF may contribute to common disorders characterised by endothelial dysfunction, providing a target for therapy.
Allopatric humpback whales of differing generations share call types between foraging and wintering grounds
Authors: Epp Mikala V. , Fournet Michelle E. H. , Silber Gregory K. , Davoren Gail K.
Published: August 2021

Humpback whales (Megaptera novaeangliae) are a cosmopolitan baleen whale species with geographically isolated lineages. Despite last sharing an ancestor ~ 2–3 million years ago, Atlantic and Pacific foraging populations share five call types. Whether these call types are also shared between allopatric breeding and foraging populations is unclear, but would provide further evidence that some call types are ubiquitous and fixed. We investigated whether these five call types were present on a contemporary foraging ground (Newfoundland, 2015–2016) and a historic breeding ground (Hawaii, 1981–1982). Calls were classified using aural/visual (AV) characteristics; 16 relevant acoustic variables were measured and a Principal Component Analysis (PCA) was used to examine within-call and between-population variation. To assess whether between-population variation influenced classification, all 16 variables were included in classification and regression tree (CART) and random forest analyses (RF). All five call types were identified in both populations. Between-population variation in combined acoustic variables (PC1, PC2, PC3) was lower within call types than among call types, and high agreement between AV and quantitative classification (CART: 83% agreement; RF: 77% agreement) suggested that acoustic characteristics were more similar within than among call types. Findings indicate that these five call types are shared across allopatric populations, generations, and behavioural contexts.
Zeolite addition to improve biohydrogen production from dark fermentation of C5/C6-sugars and Sargassum sp. biomass
Authors: Silva R. M. , Abreu A. A. , Salvador A. F. , Alves M. M. , Neves I. C. , Pereira M. A.
Published: August 2021

Thermophilic biohydrogen production by dark fermentation from a mixture (1:1) of C5 (arabinose) and C6 (glucose) sugars, present in lignocellulosic hydrolysates, and from Sargassum sp. biomass, is studied in this work in batch assays and also in a continuous reactor experiment. Pursuing the interest of studying interactions between inorganic materials (adsorbents, conductive and others) and anaerobic bacteria, the biological processes were amended with variable amounts of a zeolite type-13X in the range of zeolite/inoculum (in VS) ratios (Z/I) of 0.065–0.26 g g−1. In the batch assays, the presence of the zeolite was beneficial to increase the hydrogen titer by 15–21% with C5 and C6-sugars as compared to the control, and an increase of 27% was observed in the batch fermentation of Sargassum sp. Hydrogen yields also increased by 10–26% with sugars in the presence of the zeolite. The rate of hydrogen production increased linearly with the Z/I ratios in the experiments with C5 and C6-sugars. In the batch assay with Sargassum sp., there was an optimum value of Z/I of 0.13 g g−1 where the H2 production rate observed was the highest, although all values were in a narrow range between 3.21 and 4.19 mmol L−1 day−1. The positive effect of the zeolite was also observed in a continuous high-rate reactor fed with C5 and C6-sugars. The increase of the organic loading rate (OLR) from 8.8 to 17.6 kg m−3 day−1 of COD led to lower hydrogen production rates but, upon zeolite addition (0.26 g g−1 VS inoculum), the hydrogen production increased significantly from 143 to 413 mL L−1 day−1. Interestingly, the presence of zeolite in the continuous operation had a remarkable impact in the microbial community and in the profile of fermentation products. The effect of zeolite could be related to several properties, including the porous structure and the associated surface area available for bacterial adhesion, potential release of trace elements, ion-exchanger capacity or ability to adsorb different compounds (i.e. protons). The observations opens novel perspectives and will stimulate further research not only in biohydrogen production, but broadly in the field of interactions between bacteria and inorganic materials.
An eye tracking based virtual reality system for use inside magnetic resonance imaging systems
Authors: Qian Kun , Arichi Tomoki , Price Anthony , Dall’Orso Sofia , Eden Jonathan , Noh Yohan , Rhode Kawal , Burdet Etienne , Neil Mark , Edwards A. David , Hajnal Joseph V.
Published: August 2021

Patients undergoing Magnetic Resonance Imaging (MRI) often experience anxiety and sometimes distress prior to and during scanning. Here a full MRI compatible virtual reality (VR) system is described and tested with the aim of creating a radically different experience. Potential benefits could accrue from the strong sense of immersion that can be created with VR, which could create sense experiences designed to avoid the perception of being enclosed and could also provide new modes of diversion and interaction that could make even lengthy MRI examinations much less challenging. Most current VR systems rely on head mounted displays combined with head motion tracking to achieve and maintain a visceral sense of a tangible virtual world, but this technology and approach encourages physical motion, which would be unacceptable and could be physically incompatible for MRI. The proposed VR system uses gaze tracking to control and interact with a virtual world. MRI compatible cameras are used to allow real time eye tracking and robust gaze tracking is achieved through an adaptive calibration strategy in which each successive VR interaction initiated by the subject updates the gaze estimation model. A dedicated VR framework has been developed including a rich virtual world and gaze-controlled game content. To aid in achieving immersive experiences physical sensations, including noise, vibration and proprioception associated with patient table movements, have been made congruent with the presented virtual scene. A live video link allows subject-carer interaction, projecting a supportive presence into the virtual world.