bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 infection in UK university students: lessons from September–December 2020 and modelling insights for future student return
Authors: Enright Jessica , Hill Edward M. , Stage Helena B. , Bolton Kirsty J. , Nixon Emily J. , Fairbanks Emma L. , Tang Maria L. , Brooks-Pollock Ellen , Dyson Louise , Budd Chris J. , Hoyle Rebecca B. , Schewe Lars , Gog Julia R. , Tildesley Michael J.
Published: August 2021

In this paper, we present work on SARS-CoV-2 transmission in UK higher education settings using multiple approaches to assess the extent of university outbreaks, how much those outbreaks may have led to spillover in the community, and the expected effects of control measures. Firstly, we found that the distribution of outbreaks in universities in late 2020 was consistent with the expected importation of infection from arriving students. Considering outbreaks at one university, larger halls of residence posed higher risks for transmission. The dynamics of transmission from university outbreaks to wider communities is complex, and while sometimes spillover does occur, occasionally even large outbreaks do not give any detectable signal of spillover to the local population. Secondly, we explored proposed control measures for reopening and keeping open universities. We found the proposal of staggering the return of students to university residence is of limited value in terms of reducing transmission. We show that student adherence to testing and self-isolation is likely to be much more important for reducing transmission during term time. Finally, we explored strategies for testing students in the context of a more transmissible variant and found that frequent testing would be necessary to prevent a major outbreak.
Properties of translation operator and the solution of the eigenvalue and boundary value problems of arbitrary space–time periodic metamaterials
Authors: Elnaggar Sameh Y. , Milford Gregory N.
Published: August 2021

There is a recent interest in understanding and exploiting the intriguing properties of space–time metamaterials. In the current manuscript, the time periodic circuit theory is exploited to introduce an appropriate translation operator that fully describes arbitrary space–time metamaterials. It is shown that the underlying mathematical machinery is identical to the one used in the analysis of linear time invariant periodic structures, where time and space eigen-decompositions are successively employed. We prove some useful properties the translation operator exhibits. The wave propagation inside the space time periodic metamaterial and the terminal characteristics can be rigorously determined via the expansion in the operators eigenvectors (space–time Bloch waves). Two examples are provided that demonstrate how to apply the framework. In the first, a space time modulated composite right left handed transmission line is studied and results are verified via time domain computations. Furthermore, we apply the theory to explain the non-reciprocal behaviour observed on a nonlinear transmission line manufactured in our lab. Bloch-waves are computed from the extracted circuit parameters. Results predicted using the developed machinery agree with both measurements and time domain analysis. Although the analysis was carried out for electric circuits, the approach is valid for different domains such as acoustic and elastic media.
Extraction of urban built-up area based on the fusion of night-time light data and point of interest data
Authors: He Xiong , Zhang Zhiming , Yang Zijiang
Published: August 2021

The accurate extraction of urban built-up areas is an important prerequisite for urban planning and construction. As a kind of data that can represent urban spatial form, night-time light data has been widely used in the extraction of urban built-up areas. As one of the geographic open-source big data, point of interest (POI) data has a high spatial coupling with night-time light data, so researchers are beginning to explore the fusion of the two data in order to achieve more accurate extraction of urban built-up areas. However, the current research methods and theoretical applications of the fusion of POI data and night-time light data are still insufficient compared with the dramatically changing urban built-up areas, which needed to be further supplemented and deepened. This study proposes a new method to fuse POI data and night-time light data. The results before and after data fusion are compared, and the accuracy of urban built-up area extracted by different data and methods is analysed. The results show that the data fusion can avoid the shortage of single data and effectively improve the extraction accuracy of urban built-up areas, which is greatly helpful to supplement the study of data fusion in urban built-up areas, and also can provide decision-making guidance for urban planning and construction.
Medial amygdala ERα expression influences monogamous behaviour of male prairie voles in the field
Authors: Lambert Connor T. , Lichter James B. , Perry Adam N. , Castillo Samuel A. , Keane Brian , Cushing Bruce S. , Solomon Nancy G.
Published: August 2021

Formation of long-term pair-bonds is a complex process, involving multiple neural circuits and is context- and experience-dependent. While laboratory studies using prairie voles have identified the involvement of several neural mechanisms, efforts to translate these findings into predictable field outcomes have been inconsistent at best. Here we test the hypothesis that inhibition of oestrogen receptor alpha (ERα) in the medial amygdala of male prairie voles would significantly increase the expression of social monogamy in the field. Prairie vole populations of equal sex ratio were established in outdoor enclosures with males bred for high levels of ERα expression and low levels of prosocial behaviour associated with social monogamy. Medial amygdala ERα expression was knocked down in half the males per population. Knockdown males displayed a greater degree of social monogamy in five of the eight behavioural indices assessed. This study demonstrates the robust nature of ERα in playing a critical role in the expression of male social monogamy in a field setting.
Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma
Authors: Chen Runzhe , Li Jun , Fujimoto Junya , Hu Xin , Quek Kelly , Tang Ming , Mitra Akash , Behrens Carmen , Chow Chi-Wan , Jiang Peixin , Little Latasha D. , Gumbs Curtis , Song Xingzhi , Zhang Jianhua , Tan Dongfeng , Heymach John V. , Wistuba Ignacio , Futreal P. Andrew , Gibbons Don L. , Byers Lauren A. , Zhang Jianjun , Reuben Alexandre
Published: August 2021

Background

Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy.

Methods

In order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a young female never-smoker with late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T-cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors.

Results

We observed heterogeneous mutation, methylation, and T cell patterns across distinct metastases including a set of prevalent T cell clonotypes which were completely excluded from left-side thoracic tumors. Though a limited number of predicted neoantigens were shared, these were associated with homology of the T cell repertoire across metastases. Lastly, ratio of methylated neoantigen coding mutations was negatively associated with T-cell density, richness and clonality, suggesting neoantigen methylation may partially drive immunosuppression.

Conclusions

Our study demonstrates heterogeneous genomic and T cell profiles across synchronous metastases and how restriction of unique T cell clonotypes within an individual may differentially shape the genomic and epigenomic landscapes of synchronous lung metastases.
The Effect of Blood Viscosity on Shear-Induced Hemolysis using a Magnetically Levitated Shearing Device
Authors: Krisher James A. , Malinauskas Richard A. , Day Steven W.
Published: August 2021

Introduction

Blood contacting medical devices, including rotary blood pumps, can cause shear-induced blood damage that may lead to adverse effects in patients. Due in part to an inadequate understanding of how cell-scale fluid mechanics impact red blood cell membrane deformation and damage, there is currently not a uniformly accepted engineering model for predicting blood damage caused by complex flow fields within ventricular assist devices (VADs).

Methods

We empirically investigated hemolysis in an axial Couette flow device typical of a rotary VAD to expand our current understanding of shear-induced blood damage in two ways. First, we used a magnetically levitated device to accurately control the shear rate and exposure time experienced by blood and to minimize the effects of other uncharacterized stresses. Second, we explored the effects of both hematocrit and plasma viscosity on shear-induced hemolysis to characterize blood damage based on the viscosity-independent shear rate, rather than on shear stress.

Results

Over a shear rate range of 20,000-80,000 1/s, the Index of Hemolysis was found to be largely independent of hematocrit, bulk viscosity, or the suspension media viscosity.

Conclusion

It is recommended that future investigations of shear-induced blood damage report findings with respect to the viscosity-neutral term of shear rate, in addition to the bulk whole blood viscosity measured at an appropriate shear rate relevant to the flow conditions of the device.
New insights into the earlier evolutionary history of epiphytic macrolichens
Authors: Yang Qiuxia , Wang Yanyan , Lücking Robert , Lumbsch H. Thorsten , Wang Xin , Du Zhenyong , Chen Yunkang , Bai Ming , Ren Dong , Wei Jiangchun , Li Hu , Wang Yongjie , Wei Xinli
Published: August 2021

Lichens are well known as pioneer organisms colonizing bare surfaces such as rocks and therefore have been hypothesized to play a role in the early formation of terrestrial ecosystems. Given the rarity of fossil evidence, our understanding of the evolutionary history of lichen-forming fungi is primarily based on molecular dating approaches. These studies suggest extant clades of macrolichens diversified after the K–Pg boundary. Here we corroborate the mid-Mesozoic fossil Daohugouthallus ciliiferus as an epiphytic macrolichen that predates the K-Pg boundary by 100 Mys. Based on new material and geometric morphometric analysis, we demonstrate that the Jurassic fossil is morphologically most similar to Parmeliaceae, but cannot be placed in Parmeliaceae or other similar family-level clades forming macrolichens as these evolved much later. Consequently, a new family, Daohugouthallaceae, is proposed here to accommodate this fossil, which reveals macrolichens may have been diverse long before the Cenozoic diversification of extant lineages.
Kinetic modelling of β-cell metabolism reveals control points in the insulin-regulating pyruvate cycling pathways
Authors: Rahul Rahul , Stinchcombe Adam R , Joseph Jamie , Ingalls Brian
Published: August 2021

Insulin, a key hormone in the regulation of glucose homeostasis, is secreted by pancreatic β-cells in response to elevated glucose levels. Insulin is released in a biphasic manner in response to glucose metabolism in β-cells. The first phase of insulin secretion is triggered by an increase in the ATP:ADP ratio; the second phase occurs in response to both a rise in ATP:ADP as well as other key metabolic signals, including a rise in the NADPH:NADP+ratio. Experimental evidence indicates that pyruvate-cycling pathways play an important role in the elevation of the NADPH:NADP+ratio in response to glucose. In this work we developed a kinetic model for the tricarboxylic acid cycle and pyruvate cycling pathways. We successfully validated our model against recent experimental observations and performed local and global sensitivity analysis to identify key regulatory interactions in the system. The model predicts that the dicarboxylate carrier (DIC) and pyruvate transporter (PYC) are the most important regulators of pyruvate cycling and NADPH production. In contrast, our analysis showed that variation in the pyruvate carboxylase (PC) flux was compensated by a response in the activity of mitochondrial isocitrate dehydrogenase (ICDm) resulting in minimal effect on overall pyruvate cycling flux. The model predictions suggest starting points for further experimental investigation, as well as potential drug targets for treatment of type 2 diabetes.
Structural (dys)connectivity associates with cholinergic cell density of the nucleus basalis of Meynert in Alzheimer’s disease
Authors: Lin Chen-Pei , Frigerio Irene , Boon Baayla DC , Zhou Zihan , Rozemuller Annemieke JM , Bouwman Femke , Schoonheim Menno M , van de Berg Wilma DJ , Jonkman Laura
Published: August 2021

Cognitive deficits in Alzheimer’s disease, specifically amnestic (memory dominant) deficits, are associated with cholinergic degeneration in the basal forebrain. The cholinergic nucleus within the basal forebrain, the nucleus basalis of Meynert, exhibits local atrophy and reduced cortical tract integrity on MRI, and reveals amyloid-β and phosphorylated-tau pathology at autopsy. To better understand the pathophysiology of nucleus basalis of Meynert atrophy and its neocortical projections in Alzheimer’s disease, we utilized a combined post-mortem in-situ MRI and histopathology approach. A total of 19 Alzheimer’s disease (10 amnestic and 9 non-amnestic) and 9 non-neurological control donors underwent 3T T1-weighted MRI for anatomical delineation and volume assessment of the nucleus basalis of Meynert, and diffusion-weighted imaging for microstructural assessment of the nucleus and its projections. At subsequent brain autopsy, tissue dissection and immunohistochemistry were performed for amyloid-β, phosphorylated-tau and choline acetyltransferase. Compared to controls, we observed an MRI-derived volume reduction and altered microstructural integrity of the nucleus basalis of Meynert in Alzheimer’s disease donors. Furthermore, decreased cholinergic cell density was associated with reduced integrity of the nucleus and its tracts to the temporal lobe, specifically to the temporal pole of the superior temporal gyrus, and the parahippocampal gyrus. The association between cholinergic cell density and alteration to cortical tracts was specific for amnestic, compared to non-amnestic Alzheimer’s disease donors. Our study illustrates that the nucleus basalis of Meynert is severely affected in amnestic Alzheimer’s disease, both in terms of pathology within the nucleus, but also in terms of damage to its cortical projections, specifically to the temporal lobe, which may contribute to the observed cognitive deterioration.
Widely naturalized species are not more promiscuous in the use of different nitrogen forms, but benefit more from inorganic nitrogen
Authors: Zeng Jianjun , Liu Yanjie , van Kleunen Mark
Published: August 2021

Nitrogen (N) is an essential mineral nutrient necessary for plant growth and has been considered a crucial factor influencing invasion success. Former studies mainly focused on responses of alien plants to different levels of N availability. However, in natural soils, N comes in different forms. Few experimental studies have explored responses of naturalized alien species to different N forms, and whether such responses are related to their naturalization success globally.

We selected 22 common herbaceous species native to Germany that have all become naturalized and thus been introduced elsewhere in the world. We grew these species under six different N conditions that differed in the amount or form of N, and assessed their growth performance in a greenhouse experiment.

We found that plants produced more biomass when grown under high N levels than under low N levels, and when N was provided in inorganic form than when provided in organic form. Neither biomass production nor promiscuity to different N forms was related to naturalization success of the species. However, the biomass response to inorganic N, relative to organic N, was stronger for the widely naturalized species than for the less widely naturalized ones.

Our study shows that although the widely naturalized alien species were not more promiscuous than the less widely naturalized species, they took more advantage of the inorganic-N forms. This indicates that naturalization success might be partly driven by a species’ ability to take advantage of increased inorganic N levels.
Auditory cortex activation is modulated nonlinearly by stimulation duration: A functional near-infrared spectroscopy (fNIRS) study
Authors: Zhang Yi Fan , Lasfargue Anne , Berry Isabelle
Published: August 2021

Functional near-infrared spectroscopy (NIRS) is an increasingly popular method in hearing research. However, few studies have considered efficient stimulation parameters for fNIRS auditory experimental design. The objectives of our study are (1) to characterize the auditory hemodynamic responses to trains of white noise with increasing stimulation durations (8s, 10s, 15s, 20s) in terms of amplitude and response linearity; (2) to identify the most-efficient stimulation duration using fNIRS; and (3) to generalize results to more ecological environmental stimuli. We found that cortical activity is augmented following the increments in stimulation durations and reaches a plateau after about 15s of stimulation. The linearity analysis showed that this augmentation due to stimulation duration is not linear in the auditory cortex, the non-linearity being more pronounced for longer durations (15s and 20s). The 15s block duration that we propose as optimal precludes signal saturation, is associated with a high response amplitude and a relatively short total experimental duration. Moreover, the 15s duration remains optimal independently of the nature of presented sounds. The sum of these findings suggests that 15s stimulation duration used in the appropriate experimental setup allows researchers to acquire optimal fNIRS signal quality.
Influence of anatomical features of different brain regions on the spatial localization of fiber photometry signals
Authors: Montinaro Cinzia , Pisanello Marco , Bianco Marco , Spagnolo Barbara , Pisano Filippo , Balena Antonio , De Nuccio Francesco , Lofrumento Dario Domenico , Verri Tiziano , De Vittorio Massimo , Pisanello Ferruccio
Published: August 2021

Fiber photometry is widely used in neuroscience labs for in vivo detection of functional fluorescence from optical indicators of neuronal activity with a simple optical fiber. The fiber is commonly placed next to the region of interest to both excite and collect the fluorescence signal. However, the path of both excitation and fluorescence photons is altered by the uneven optical properties of the brain, due to local variation of the refractive index, different cellular types, densities and shapes. Nonetheless, the effect of the local anatomy on the actual shape and extent of the volume of tissue that interfaces with the fiber has received little attention so far. To fill this gap, we measured the size and shape of fiber photometry efficiency field in the primary motor and somatosensory cortex, in the hippocampus and in the striatum of the mouse brain, highlighting how their substructures determine the detected signal and the depth at which photons can be mined. Importantly, we show that the information on the spatial expression of the fluorescent probes alone is not sufficient to account for the contribution of local subregions to the overall collected signal, and it must be combined with the optical properties of the tissue adjacent to the fiber tip.
The sodium leak channel NALCN encodes the major background sodium ion conductance in mouse anterior pituitary cells
Authors: Belal Marziyeh , Mucha Mariusz , Monteil Arnaud , Winyard Paul G , Pawlak Robert , Walker Jamie J. , Tabak Joel , Belle Mino D C
Published: August 2021

The pituitary gland produces and secretes a variety of hormones that are essential to life, such as for the regulation of growth and development, metabolism, reproduction, and the stress response. This is achieved through an intricate signalling interplay between the brain and peripheral feedback signals that shapes pituitary cell excitability by regulating ion channel properties of these cells. In addition, endocrine anterior pituitary cells fire action potentials spontaneously to regulate intracellular calcium ([Ca2+]i) level, an essential signalling conduit for hormonal secretion. To this end, pituitary cells have to critically regulate their resting membrane potential (RMP) close to firing threshold, but the molecular identity of the ionic mechanisms involved remains largely unknown. Here, we revealed that the sodium leak channel NALCN, known to modulate neuronal excitability elsewhere in the brain, acts to regulate excitability in the mouse anterior endocrine pituitary cells. Using viral transduction combined with powerful electrophysiology methods and calcium imaging, we show that NALCN forms the major Na+ leak conductance in these cells, appropriately tuning cellular RMP for sustaining spontaneous firing activity. Genetic interruption of NALCN channel activity drastically hyperpolarised the cells, suppressing firing and ([Ca2+]i) oscillations. Remarkably, we uncover that NALCN conductance formed a very small fraction of the total cell conductance, but yet had a profound impact on pituitary cell excitability. Our results also provide a possible mechanism through which hypothalamic and hormone feedback signals can powerfully affect pituitary activity to influence hormonal function.
Bacteria.guru: comparative transcriptomics and co-expression database for bacterial pathogens
Authors: Lim Peng Ken , Davey Emilia E , Wee Sean , Seetoh Wei Song , Goh Jong Ching , Zheng Xinghai , Ann Phang Sean Kia , Kai Seah Eugene Sheng , Zhen Ng Janice Wan , Hui Wee Xavier Jia , Hui Quek Aloysius Jun , Lim Jordan JingHeng , Rodrigues Edbert Edric , Lee Heesoo , Lim Chin Yong , Tan Wei Zhi , Dan Yuet Ruh , Lee Bronson , Le Chee Samuel En , En Lim Zachary Ze , Guan Jia Sheng , Le Tan Ivan Jia , Arong Trinidad Jeremiah , Mutwil Marek
Published: August 2021

The bacterial kingdom comprises unicellular prokaryotes able to establish symbioses from mutualism to parasitism. To combat bacterial pathogenicity, we need an enhanced understanding of gene function and regulation, which will mediate the development of novel antimicrobials. Gene expression can predict gene function, but there lacks a database enabling expansive inter- and intraspecific exploration of gene expression profiles and co-expression networks for bacteria. To address this, we integrated the genomic and transcriptomic data of the 17 most notorious and studied bacterial pathogens, creating bacteria.guru, an interactive database that can identify, visualize, and compare gene expression profiles, co-expression networks, functionally enriched clusters, and gene families across species. Through illustrating antibiotic resistance mechanisms in P. aeruginosa, we demonstrate that bacteria.guru could potentially aid the discovery of multi-faceted antibiotic targets. Hence, we believe bacteria.guru will facilitate future bacterial research.

Availability

The database and co-expression networks are freely available from https://bacteria.guru/. The sample annotations are found in the supplemental data.
The socioeconomic factors that led to unemployment under COVID-19 pandemic among Japanese workers: a prospective cohort study
Authors: Kuroishi Makiko , Nagata Tomohisa , Hino Ayako , Tateishi Seiichiro , Ogami Akira , Tsuji Mayumi , Matsuda Shinya , Mori Koji , Fujino Yoshihisa ,   the CORoNaWork project
Published: August 2021

Objectives

To examine the relationship between socioeconomic factors and unemployment among workers during COVID-19 pandemic in Japan.

Design

A prospective cohort study, follow-up from December 22–25, 2020 through February 18–19, 2021.

Setting

The panelists registered with an Internet survey company

Participants

A cluster random sample of 33,087 workers with stratification by sex, job type, and region among Japan’s working population

Main outcomes and measures

Unemployment between December 2020 and February 2021

Results

Among the 19,941 participants, 725 (3.6%) had experienced unemployment. Multivariate analysis showed that the significant high unemployment for women (compared to men); younger age (compared to older age); being married (spouse not working), bereaved or divorced, and unmarried (compared to married (spouse working)); annual household income less than 6 million yen, (compared to more than 10 million yen); junior high or high school, vocational school, junior college, or technical school (compared to graduate school); and temporary or contract employees, self-employed, agriculture, forestry, or fishing (compared to general employees).

Conclusions

COVID-19 appears to have created difficulties for the vulnerable groups. This suggests the need for employment and economic support for such individuals.

Strengths and limitations of this study

Under the pandemic of COVID-19, we found that unemployment was associated with socioeconomic factors such as age, sex, marriage, income, education and occupation.

Our findings suggest that in the event of a major epidemic, resulting in unemployment among vulnerable segments of the labour market, regardless of whether workers themselves are infected.

It was unclear why the participants had experienced unemployment

This study was conducted as an Internet survey, so the generalizability of our results is limited.
Trends and Intensity of Human Rhinovirus Invasions in Kilifi, Coastal Kenya Over a Twelve-Year Period, 2007-2018
Authors: Morobe John Mwita , Kamau Everlyn , Murunga Nickson , Gatua Winfred , Luka Martha M. , Lewa Clement , Cheruiyot Robinson , Mutunga Martin , Odundo Calleb , Nokes D James , Agoti Charles N.
Published: August 2021

Background

Human rhinovirus (HRV) is an ubiquitous pathogen and the principal etiologic agent of common cold. Despite the high frequency of HRV infections, data describing its long-term epidemiological patterns in a single population remain limited.

Methods

We analysed 1,070 VP4/VP2 genomic region sequences obtained from samples collected between 2007-2018 from hospitalised paediatric patients (< 60 months) with acute respiratory disease in Kilifi County Hospital on the Kenya Coast.

Results

Of 7,231 children enrolled, HRV was detected in 1,497 (20.7%) andVP4/VP2 sequences were recovered from 1,070 samples (71.5%). A total of 144 different HRV types were identified (67 HRV-A, 18 HRV-B and 59 HRV-C) and at any time-point, several types co-circulated with alternating predominance. Within types multiple genetically divergent variants were observed. Ongoing HRV infections appeared to be a combination of (i) persistent types (observed up to seven consecutive months), (ii) reintroduced genetically distinct variants and (iii) new invasions (average of 8 new types, annually).

Conclusion

Sustained HRV presence in the Kilifi community is mainly due to frequent invasion by new types and variants rather than prolonged circulation of locally established strains.
Strigo-D2 – a bio-sensor for monitoring the spatio-temporal pattern of strigolactone signaling in intact plants
Authors: Song Changzheng , Zhao Jiao , Guichard Marjorie , Shi Dongbo , Grossmann Guido , Schmitt Christian , Jouannet Virginie , Greb Thomas
Published: August 2021

Strigolactones (SLs) are a class of plant hormones modulating developmental programs in response to endogenous and exogenous stimuli and mediating biotic interactions. However, a comprehensive view on the spatio-temporal pattern of SL signaling has not been established and tools for a systematic in planta analysis do not exist. Here, we present Strigo-D2, a genetically encoded ratiometric SL signaling sensor, allowing the examination of SL signaling distribution with cellular resolution and its rapid response to altered SL levels in intact plants. By monitoring the abundance of a truncated and fluorescently labeled SUPPRESSOR OF MAX2 1-LIKE 6 (SMXL6) protein, a proteolytic target of the SL signaling machinery, we show that all cell types investigated have the capacity to respond to changes in SL levels but with very different dynamics. In particular, SL signaling is pronounced in vascular cells but low in guard cells and the meristematic region of the root. We also show that other hormones leave Strigo-D2 activity unchanged indicating that initial SL signaling steps work in isolation from other hormonal signaling pathways. Specificity and spatio-temporal resolution of Strigo-D2 underline the value of the sensor for monitoring SL signaling in a broad range of biological contexts and with highly instructive analytical depth.
The two-component response regulator OrrA confers dehydration tolerance by regulating anaKa expression in the cyanobacterium Anabaena sp. strain PCC 7120
Authors: Kimura Satoshi , Sato Miho , Fan Xingyan , Ohmori Masayuki , Ehira Shigeki
Published: August 2021

The aquatic cyanobacterium Anabaena sp. strain PCC 7120 exhibits dehydration tolerance. The regulation of gene expression in response to dehydration is crucial for the acquisition of dehydration tolerance, but the molecular mechanisms underlying dehydration responses remain unknown. In this study, the functions of the response regulator OrrA in the regulation of salt and dehydration responses were investigated. Disruption of orrA abolished or diminished the induction of hundreds of genes in response to salt stress and dehydration. Thus, OrrA is a principal regulator of both stress responses. In particular, OrrA plays a crucial role in dehydration tolerance because an orrA disruptant completely lost the ability to regrow after dehydration. Moreover, in the OrrA regulon, anaKa encoding a protein of unknown function was revealed to be indispensable for dehydration tolerance. OrrA and AnaK are conserved among the terrestrial cyanobacteria, suggesting their conserved functions in dehydration tolerance in cyanobacteria.
Cooled SPAD array detector for low light-dose fluorescence laser scanning microscopy
Authors: Slenders Eli , Perego Eleonora , Buttafava Mauro , Tortarolo Giorgio , Conca Enrico , Zappone Sabrina , Pierzynska-Mach Agnieszka , Villa Federica , Petrini Enrica Maria , Barberis Andrea , Tosi Alberto , Vicidomini Giuseppe
Published: August 2021

The single-photon timing and sensitivity performance and the imaging ability of asynchronous-readout single-photon avalanche diode (SPAD) array detectors have opened up enormous perspectives in fluorescence (lifetime) laser scanning microscopy (FLSM), such as super-resolution image scanning microscopy and high-information content fluorescence fluctuation spectroscopy (FFS). However, the strengths of these FLSM techniques depend on the many different characteristics of the detector, such as dark-noise, photon-detection efficiency, after-pulsing probability, and optical-cross talk, whose overall optimization is typically a trade-off between these characteristics. To mitigate this trade-off, we present a novel SPAD array detector with an active cooling system, which substantially reduces the dark-noise without significantly deteriorating any other detector characteristics. In particular, we show that lowering the temperature of the sensor to −15°C significantly improves the signal-to-noise ratio due to a 10-fold decrease in the dark-count rate compared to room temperature. As a result, for imaging, the laser power can be decreased by more than a factor of three, which is particularly beneficial for live-cell super-resolution imaging, as demonstrated in fixed and living cells expressing GFP-tagged proteins. For FFS, together with the benefit of the reduced laser power, we show that cooling the detector is necessary to remove artifacts in the correlation function, such as spurious negative correlations observed in the hot elements of the detector, i.e., elements whose dark-noise is substantially higher than the median value. Overall, this detector represents a further step towards the integration of SPAD array detectors in any FLSM system.

SIGNIFICANCE

Single-photon avalanche diode (SPAD) array detectors are revolutionizing fluorescence laser-scanning microscopy (FLSM). Thanks to their single-photon timing and sensitivity ability and their imaging faculty, a SPAD array detector transforms any FLSM into a super-resolution microscope, and opens a whole range of possibilities for the study of sample dynamics by means of fluorescence fluctuation spectroscopy (FFS). However, dark-noise can be a severe problem for both imaging and FFS. For imaging, the signal overcomes noise only for a relatively high illumination intensity, which can be detrimental for live-cell experiments. For FFS, the noise leads to artifacts in the correlation curves, potentially leading to wrong conclusions about the sample. We show that lowering the temperature of the detector to −15°C solves both problems
Modulating D1 rather than D2 receptor-expressing spiny-projection neurons corresponds to optimal antipsychotic effect
Authors: Yun Seongsik , Yang Ben , Martin Madison M. , Yeh Nai-Hsing , Contractor Anis , Parker Jones G.
Published: August 2021

Overactive dopamine transmission in psychosis is predicted to unbalance striatal output via D1- and D2-dopamine receptor-expressing spiny-projection neurons (SPNs). Antipsychotic drugs are thought to re-balance this output by blocking D2-receptor signaling. Here we imaged D1- and D2-SPN Ca2+dynamics in mice to determine the neural signatures of antipsychotic effect. Initially we compared effective (clozapine and haloperidol) antipsychotics to a candidate drug that failed in clinical trials (MP-10). Clozapine and haloperidol normalized hyperdopaminergic D1-SPN dynamics, while MP-10 only normalized D2-SPN activity. Clozapine, haloperidol or chemogenetic manipulations of D1-SPNs also normalized sensorimotor gating. Given the surprising correlation between clinical efficacy and D1-SPN modulation, we evaluated compounds that selectively target D1-SPNs. D1R partial agonism, antagonism, or positive M4 cholinergic receptor modulation all normalized the levels of D1-SPN activity, locomotion, and sensorimotor gating. Our results suggest that D1-SPN activity is a more relevant therapeutic target than D2-SPN activity for the development of effective antipsychotics.
Phenotyping Antidepressant Treatment Response with Deep Learning in Electronic Health Records
Authors: Sheu Yi-han , Magdamo Colin , Miller Matthew , Das Sudeshna , Blacker Deborah , Smoller Jordan W.
Published: August 2021

Efficient, accurate phenotyping for antidepressant treatment response in electronic health records (EHRs) could facilitate precision psychiatry applications but remains a challenge. Increasingly, artificial intelligence methods using “deep learning” applied to clinical data have shown promise in complex classification problems. Here, we systematically evaluate the performance of eight deep-learning-based natural language processing models in classifying response to antidepressants in a large real-world healthcare setting. We obtained data spanning 1990-2018 for adults with depression and a co-occurring antidepressant prescription from the EHR data warehouse of the Mass General Brigham healthcare system (n=111,572). Clinical notes were collected for the following time windows after antidepressant initiation: (1) 2 days to 4 weeks, (2) 4–12 weeks, and (3) 12–26 weeks. A stratified random sample of these note sets (total 4,299 across time periods) were manually reviewed to classify response status as “improved” or “no evidence of improvement” in depression symptoms. All models performed well, with areas under the receiver operator curve (AUROC) of at least 0.80. Positive predictive values (PPVs) ranged from 0.72 – 0.91. In general, models incorporating more information-dense and longer text sequences performed better than others. The best performing model (Longformer-large with sliding window) had an AUROC = 0.88 and PPV = 0.84 at a specificity of 0.88. Our results indicate that deep learning methods applied to EHR data can accurately classify antidepressant response in a real-world healthcare setting. Automated treatment response classification may facilitate a range of research and clinical decision support applications.
Assessing ventilation strategies in a school with observed indoor air problems
Authors: Uotila Ulrika , Saari Arto , Junnonen Juha-Matti Kalevi , Eskola Lari
Published: August 2021

Purpose

Poor indoor air quality in schools is a worldwide challenge that poses health risks to pupils and teachers. A possible response to this problem is to modify ventilation. Therefore, the purpose of this paper is to pilot a process of generating alternatives for ventilation redesign, in an early project phase, for a school to be refurbished. Here, severe problems in indoor air quality have been found in the school.

Design/methodology/approach

Ventilation redesign is investigated in a case study of a school, in which four alternative ventilation strategies are generated and evaluated. The analysis is mainly based on the data gathered from project meetings, site visits and the documents provided by ventilation and condition assessment consultants.

Findings

Four potential strategies to redesign ventilation in the case school are provided for decision-making in refurbishment in the early project phase. Moreover, the research presents several features to be considered when planning the ventilation strategy of an existing school, including the risk of alterations in air pressure through structures; the target number of pupils in classrooms; implementing and operating costs; and the size of the space that ventilation equipment requires.

Research limitations/implications

As this study focusses on the early project phase, it provides viewpoints to assist decision-making, but the final decision requires still more accurate calculations and simulations.

Originality/value

This study demonstrates the decision-making process of ventilation redesign of a school with indoor air problems and provides a set of features to be considered. Hence, it may be beneficial for building owners and municipal authorities who are engaged in planning a refurbishment of an existing building.
Influences on the career intentions of millennials; a view from the United Arab Emirates
Authors: Kemp Linzi J. , McLoughlin Linda
Published: August 2021

Purpose

The study aims to discover influences on the career intentions of millennials in the United Arab Emirates (UAE).

Design/methodology/approach

Qualitative data about career intentions were collected from a sample group (#50) of students at an international university in the UAE. Participant's responses were recorded in five groups, composed of undergraduates, males and females, expatriates and citizens. Transcripts were formed of these data, which were thematically analysed to identify influences on career intentions.

Findings

Four emergent themes were identified of influences on career intentions: (1) influenced by societal obligations, (2) influenced by a traditional approach to career plans; (3) influenced by own aspirations; (4) influenced by country considerations. Findings recognised career intentions for this sample group resulted from cultural orientation and millennial's characteristics.

Research limitations/implications

The study was limited by the one country/one university context and a direction is to replicate for an expanded sample group and/or to extend this research scope to other countries.

Practical implications

These findings have implications for university career advising, and the recruitment and retention of millennials in the UAE by international companies.

Originality/value

This is an original study in its exploration of influences on millennial's career intentions in the UAE. Research value lies in the addition of academic knowledge about those millennials' future career intentions.
Coffee tourism in Portugal: an attraction case study
Authors: Dinis Maria Gorete , Melo Carla Salgueiro , Sousa João Miguel Batista Miguéns
Published: August 2021

Purpose

This paper aims to demonstrate how attractions and experiences associated with coffee can contribute to dissemination and knowledge of its culture and to the development of coffee tourism in Portugal.

Design/methodology/approach

A case study methodology is applied, focusing on the Coffee Science Centre – Delta Interpretation, Scientific and Technological Promotion and Tourism Promotion Centre (CCC).

Findings

Results indicate that this type of attraction can be used to disseminate coffee culture by providing differentiating and enriching experiences to tourists, and most importantly, by developing tourism in a sustainable way.

Originality/value

This study contributes to expanding the knowledge on coffee tourism, an under-explored field of study, particularly in Portugal, where to the authors knowledge, there is no applied research within this scope.
A priority action roadmap for women's economic empowerment (PARWEE) amid COVID-19: a co-creation approach
Authors: Bonin Sandrine , Singh Wafa , Suresh Veena , Rashed Tarek , Uppaal Kuiljeit , Nair Rajiv , Bhavani Rao R.
Published: August 2021

Purpose

The study aims to co-create a “priority action roadmap for women's economic empowerment” based on women's top priorities to charting recovery directions. Doing so contributes to the growing body of knowledge on COVID-19 literature in at least four areas: assessing COVID-19 impacts on women entrepreneurs; mapping these impacts with four interdependent women's entrepreneurial ecosystem components; innovating a co-creation methodology based on remote participatory research; and providing a replicable model to perform action-oriented research in the context of COVID-19 impacts.

Design/methodology/approach

A co-creation methodology is proposed, combining systems-thinking and remote participatory research to engage women entrepreneurs and institutional stakeholders to prioritize impact, response actions and recovery needs in the wake of COVID-19. A ranking exercise using the analytic hierarchy process was used to derive ranking and assess user inputs' consistency.

Findings

The study exemplifies the integration of participatory methods and mathematical tool to engage stakeholders in prioritizing recovery work. PARWEE action items ranked by entrepreneurs and vetted by institutional stakeholders cover: access to finances, capacity building, health care, public and private partnership, marketing opportunities and formation of active advocacy groups to voice out women entrepreneurs' needs to institutional stakeholders. Results show a slight difference in the ranking of priority actions between experience owners and fresh starters.

Originality/value

This study innovated a new co-creation methodology for remotely engaging stakeholders of the women's entrepreneurial ecosystem, which is grounded in evidence and provides a replicable model for performing action-oriented research.
Optimized scheduling techniques focused on powerful heuristics leveraging cloud services soft computing
Authors: P. Veerendra , Rao Thirupathi
Published: August 2021

Purpose

Determining the roles of multiple CSPs is important because it affects job costs and time off. The primary objective of this work is to ensure an efficient and complex distribution of resources in cloud-based computing. Workflow study of various algorithms such as ant colony optimization (ACO), differential evolution algorithm, genetic algorithm, particle swarm optimization (PSO), hybridization of the above algorithms (ADGP). For research, CSP’s tools are put all over the world.

Design/methodology/approach

The main objective of this study is to effectively introduce cloud-based computing in CSPs. The algorithm minimizes resource response time and overall workflow tasks. It seeks to improve load balancing by modifying the algorithm to support load balancing. In the proposed multipurpose scheduling methods, the ADGP algorithm performs better than any other proposed algorithm during the resource response. This algorithm was found to be superior to the selected 200 sources and thousands of tasks. It reduces resource response time by copying service nodes through several sites. As this algorithm moves faster to the best solution, the response time of the resource is reduced compared to other algorithms.

Findings

Hybrid ACOs perform best when it comes to resource management when workloads are uniformly spread across multiple virtual machines. However, hybrids PSOs are better suited to choosing the best options to minimize costs. Overall, an optimal cloud-based scheduling solution can be successfully simulated using CloudSim in CSP to share resources between end-users to support consumers and users effectively.

Originality/value

Hybrid ACOs perform best when it comes to resource management when workloads are uniformly spread across multiple virtual machines. However, hybrids PSOs are better suited to choosing the best options to minimize costs. Overall, an optimal cloud-based scheduling solution can be successfully simulated using CloudSim in CSP to share resources between end-users to support consumers and users effectively.
Business to business (B2B) alliances in the healthcare industry: a review of research trends and pertinent issues
Authors: Madanaguli Arun Thirumalesh , Dhir Amandeep , Talwar Shalini , Singh Gurmeet , Escobar Octavio
Published: August 2021

Purpose

This study aims to find, analyse and synthesise the body of literature on how different health-care businesses form business-to-business (B2B) alliances. By doing so, this study seeks to identify visible research gaps to suggest future research questions and develop a conceptual framework to set a future research agenda.

Design/methodology/approach

The study uses the time-tested systematic literature review method to identify 57 studies that have addressed B2B relationships in the health-care industry. Thereafter, a qualitative analysis is performed to delineate the research profile and synthesise the key themes examined in the selected studies.

Findings

The qualitative analysis uncovers two key thematic foci: types and purposes of B2B relationships and pertinent issues in continued B2B relationships. Within these themes, the authors highlight different types of firms and their reasons for engaging in B2B relationships. The authors also summarise various issues that these firms deal with in such relationships. Finally, the authors highlight the limitations in the existing research and suggest future research questions to address them. The findings are summarised in a conceptual framework.

Originality/value

Although several reviews exist that evaluate the state-of-the-art research on B2B relationships, very few have examined the same in the context of health care. This review adds value to the research by providing a comprehensive overview of the existing findings in the area to encourage future research through a conceptual framework.