bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning approaches to identify sleep genes
Authors: Lee Yin Yeng , Endale Mehari , Wu Gang , Ruben Marc D , Francey Lauren J , Morris Andrew R , Choo Natalie Y , Anafi Ron C , Smith David F , Liu Andrew Chuanyin , Hogenesch John B
Published: April 2021

Genetics impacts sleep, yet, the molecular mechanisms underlying sleep regulation remain elusive. We built machine learning (ML) models to predict genes based on their similarity to known sleep genes. Using a manually curated list of 109 labeled sleep genes, we trained a prediction model on thousands of published datasets, representing circadian, immune, sleep deprivation, and many other processes. Our predictions fit with prior knowledge of sleep regulation and also identify several key genes/pathways to pursue in follow-up studies. We tested one of our findings, the NF-κB pathway, and showed that its genetic alteration affects sleep duration in mice. Our study highlights the power of ML to integrate prior knowledge and genome-wide data to study genetic regulation of sleep and other complex behaviors.
Online Closed-Loop Real-Time tES-fMRI for Brain Modulation: Feasibility, Noise/Safety and Pilot Study
Authors: Mulyana Beni , Tsuchiyagaito Aki , Smith Jared , Misaki Masaya , Kuplicki Rayus , Soleimani Ghazaleh , Rashedi Ashkan , Shereen Duke , Bergman Til Ole , Cheng Samuel , Paulus Martin , Bodurka Jerzy , Ekhtiari Hamed
Published: April 2021

Recent studies suggest that transcranial electrical stimulation (tES) can be performed during functional magnetic resonance imaging (fMRI). The novel approach of using concurrent tES-fMRI to modulate and measure targeted brain activity/connectivity may provide unique insights into the causal interactions between the brain neural responses and psychiatric/neurologic signs and symptoms, and importantly, guide the development of new treatments. However, tES stimulation parameters to optimally influence the underlying brain activity in health and disorder may vary with respect to phase, frequency, intensity and electrode’s montage. Here, we delineate how a closed-loop tES-fMRI study of frontoparietal network modulation can be designed and performed. We also discuss the challenges of running a concurrent tES-fMRI, describing how we can distinguish clinically meaningful physiological changes caused by tES from tES-related artifacts. There is a large methodological parameter space including electrode types, electrolytes, electrode montages, concurrent tES-fMRI hardware, online fMRI processing pipelines and closed-loop optimization algorithms that should be carefully selected for closed-loop tES-fMRI brain modulation. We also provide technical details on how safety and quality of tES-fMRI settings can be tested, and how these settings can be monitored during the study to ensure they do not exceed safety standards. The initial results of feasibility and applicability of closed-loop tES-fMRI are reported and potential hypotheses for the outcomes are discussed.

Highlight points

Methodological details of a closed-loop tES-fMRI study protocol are provided.

The protocol is performed successfully on a frontoparietal network without side-effects.

The temperature of electrodes in concurrent tES-fMRI remains in the safe range.

Properly setup concurrent tES does not introduce MRI artifacts and noise.

Simplex optimizer could be used to find an optimal tES stimulation parameter.
Escherichia coliCryptic Prophages Sense Nutrients to Control Persister Cell Resuscitation
Authors: Song Sooyeon , Kim Jun-Seob , Yamasaki Ryota , Oh Sejong , Benedik Michael , Wood Thomas K.
Published: April 2021

We determined previously that some cryptic prophages are not genomic junk but instead enable cells to combat myriad stresses as part of an active stress response. However, how these phage fossils affect the extreme stress response of dormancy; i.e., how cryptic prophages affect persister cell formation and resuscitation, has not been fully explored. Persister cells form as a result of stresses such as starvation, antibiotics, and oxidative conditions, and resuscitation of these persister cells likely causes recurring infections such as those associated with tuberculosis, cystic fibrosis, and Lyme disease. Unlike for the active stress response, here we find that deletion of each of the nineEscherichia colicryptic prophages has no effect on persister cell formation. Strikingly, elimination of each cryptic prophage results in an increase in persister cell resuscitation with a dramatic increase in resuscitation upon deleting all nine prophages. This increased resuscitation includes eliminating the need for a carbon source and is due to activation of the phosphate import system as a result of inactivating transcriptional regulator AlpA of the CP4-57 cryptic prophage, since we found ΔalpAincreases persister resuscitation, and AlpA represses phosphate regulator PhoR. Therefore, we report a novel cellular stress mechanism controlled by cryptic prophages: regulation of phosphate uptake which controls the exit of the cell from dormancy and prevents premature resuscitation in the absence of nutrients.
A ribosomal protein variant that confers macrolide resistance differentially regulates acid resistance, catabolism, and biofilm formation related genes inEscherichia coli
Authors: Franklin Elizabeth A. , Worthan Sarah B. , Pham Chi , Yap Mee-Ngan F. , Cruz-Vera Luis R.
Published: April 2021

Mutational changes in bacterial ribosomes that confer antibiotic resistance decrease cell fitness. Determining the genetic factors that interconnect antibiotic resistance and cell fitness is critical in the fight against bacterial infections. Here, we describe gene expression and phenotypic changes presented inEscherichia colicells carrying an uL22(K90D) mutant ribosomal protein, which showed growth defects and resistance to macrolide antibiotics. Ribosome profiling analyses revealed reduced expression of operons involved in catabolism, electron transportation, indole production, and lysine-decarboxylase acid resistance. In general, ribosome occupancy was increased at rare codons while translation initiation of proximal genes in several of the affected operons was substantially reduced. Decline of the activity of these genes was accompanied by increased expression of macrolide multidrug efflux pumps, the glutamate-decarboxylase regulon, and the autoinducer-2 metabolic regulon. In concordance with these changes, uL22(K90D) mutant cells grew better in acidic conditions and generated more biofilm in static cultures than their parental strain. Our work provides new insights on how mutations in ribosomal proteins induce the acquisition of macrolide and pH resistance, and increase the ability to generate biofilms.
An Engineered Contact Lens for Passive and Sustained Release of Lifitegrast, an Anti-Dry Eye Syndrome Drug
Authors: Mu Changhua , Lee Victoria , Liu Yiran , Han Ying , Marriott Gerard
Published: April 2021

Lifitegrast is an FDA-approved drug that inhibits T-cell mediated inflammation associated with dry eye syndrome (DES). Lifitegrast is a potent inhibitor of the interaction between LFA-1 on T-cells and ICAM-1 on endothelial cells at the ocular surface. While effective in treating DES, 5% (81.2 mM) lifitegrast has low drug utilization and elicits off-target effects. Here we engineer contact lenses to release therapeutically-relevant doses of lifitegrast to every tear film for up to 10-hours. Lifitegrast is coupled to the polymer of the soft hydrogel lens via a photolabile (caged) crosslinker. Exposures of the lens to the 400-430 nm wavelengths of indoor daylight excite the caged crosslinker molecules and trigger a bond-cleavage reaction that releases authentic lifitegrast passively to the tear film. The photoproduct of the reaction remains chemically-linked to the polymer of the single-use lens. Our studies show that passive exposures of the lens to indoor light would generate an average of 990 nM lifitegrast to every tear film in a zero-order reaction for up to 10-hours. This concentration exceeds theKdfor the interaction between ICAM-1 and LFA-1 by ∼330-fold and would sustain inhibition of inflammatory responses at the ocular surface. The amount of lifitegrast released from the lens increases during exposures to outdoor sunlight. Over a 10-hour exposure to indoor light, a single lens would release 0.44% of the lifitegrast present in two drops of commercial 5% lifitegrast. Compared to tear-drop approaches, our engineered lenses would sustain the passive delivery of therapeutically-relevant doses of lifitegrast over a longer period, and exhibit improved drug utilization at a lower cost. Our technology could easily be integrated into daily-use contact lenses in order to prevent inflammation at the ocular surface, dry-eye and contact lens-mediated discomfort.

Graphical Abstract
Latitudinal cline in hypoxia tolerance does not result in correlated acid tolerance inTigriopus californicus
Authors: Deconinck Aimee , Willett Christopher
Published: April 2021

Intertidal organisms must tolerate a wide range of environmental parameters each day which may result in tolerance to multiple stressors correlating. The intertidal copepodTigriopus californicusexperiences diurnal variation in dissolved oxygen levels and pH as the opposing processes of photosynthesis and cellular respiration lead to coordinated highs during the day and lows at night. While environmental parameters with overlapping spatial gradients frequently result in correlated traits, less attention has been given to exploring temporally correlated stressors. We investigated whether hypoxia tolerance correlated with acid tolerance by testing the hypoxia and low pH stress tolerance of 6 genetically differentiated populations ofT. californicus. We checked for similarities in tolerance for the two stressors by latitude, sex, size, and time since collection as predictors. We found that although hypoxia tolerance correlated with latitude, acid tolerance did not, and no predictor was significant for both stressors. We concluded that temporally coordinated exposure to low pH and low oxygen did not result in populations developing equivalent tolerance for both.
Quarantine, relaxation and mutation explaining the CoViD-19 epidemic in São Paulo State (Brazil)
Authors: Yang Hyun Mo , Lombardi Junior Luis Pedro , Castro Fabio Fernandes Morato , Yang Ariana Campos
Published: April 2021

Background

The continuous SARS-CoV-2 transmission in several countries could contribute to the mutations’ appearance. The circulation of more virulent variants may increase the number of severe CoViD-19 needing hospital care and fatalities hugely.

Methods

The partial quarantine in São Paulo State and further relaxation associated with the mutations are explained by a mathematical model based on the CoViD-19 natural history encompassing the age-dependent fatality. The model parameters were fitted considering the observed data from São Paulo State.

Results

The partial quarantine was explained by the less virulent SARS-CoV-2 transmission, but the relaxation alone could not explain the epidemic observed in São Paulo State. However, more virulent variants plus the transmission among isolated individuals explained the increased CoViD-19 fatalities.

Conclusions

The model described the CoViD-19 epidemic in São Paulo State by considering the partial quarantine, relaxation and mutations. The model provided a potential epidemiological scenario in the absence of mass vaccination.
Transcriptional Control of Brain Tumour Stem Cells by a Carbohydrate Binding Protein
Authors: Sharanek Ahmad , Burban Audrey , Hernandez-Corchado Aldo , Madrigal Ariel , Fatakdawala Idris , Najafabadi Hamed S , Soleimani Vahab D , Jahani-Asl Arezu
Published: April 2021

Brain tumour stem cells (BTSCs) and intratumoural heterogeneity represent major challenges in glioblastoma therapy. Here, we report that theLGALS1gene, encoding the carbohydrate binding protein, galectin1, is a key regulator of BTSCs and glioblastoma resistance to therapy. Genetic deletion ofLGALS1alters BTSC gene expression profiles and results in downregulation of gene sets associated with mesenchymal subtype of glioblastoma. Using a combination of pharmacological and genetic approaches, we establish that inhibition ofLGALS1signalling in BTSCs impairs self-renewal, suppresses tumourigenesis, prolongs lifespan, and improves glioblastoma response to ionizing radiation in preclinical animal models. Mechanistically, we show thatLGALS1is a direct transcriptional target of STAT3 with its expression robustly regulated by the ligand OSM. Importantly, we establish that galectin1 forms a complex with the transcription factor HOXA5 to reprogram BTSC transcriptional landscape. Our data unravel an oncogenic signalling pathway by which galectin1/HOXA5 complex maintains BTSCs and promotes glioblastoma.
A measurement model of project control systems success for engineering and construction projects case study: contractor companies in Saudi's petroleum and chemical industry
Authors: Jawad Sahar , Ledwith Ann
Published: April 2021

Purpose

The purpose of this paper is to presents a new modeling approach that provides a measurement tool for evaluating the effectiveness of Project Control Systems (PCS) and the improvement of the project control capability as a part of an organization's project management processes.

Design/methodology/approach

This study used a project management maturity approach to develop a measurement model of PCS success. The key elements in this model have been identified using the Fuzzy Analytic Hierarchy Process (FAHP) method to analyze data from a case study involving contractor companies in Saudi's petroleum and chemical industry.

Findings

The results identified six critical elements for PCS success: (1) Change Management, (2) Earned Value, (3) Baselined Plan, (4) Resource Loaded, (5) Progress Method and (6) Governance Program. In addition, Project Forecasting and Corrective Action Verification were identified as the main areas where clients and contractors need to focus for the effective deployment of a PCS.

Practical implications

The results of this study were used to create a PCS Maturity Model (PCSMM) and a PCS Success Index (PCSSI). The value of this index can help project managers to identify the maturity level of their PCS and improvement areas that lead to enhanced project performance.

Originality/value

This research presents an alternative maturity model for PCS assessment that provides a practical tool to identify areas for improving the critical elements of PCS success. The study draws a clear distinction between overall project success and the success of the PCS.
Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress
Authors: Baral Hritu , Sekiguchi Akiko , Uchiyama Akihiko , Nisaa Amalia Syahla , Yamazaki Sahori , Inoue Yuta , Yokoyama Yoko , Ogino Sachiko , Torii Ryoko , Hosoi Mari , Akai Ryoko , Iwawaki Takao , Ishikawa Osamu , Motegi Sei‐ichiro
Published: April 2021

Oxidative stress has been reported to play an important role in the pathogenesis of skin fibrosis in systemic sclerosis (SSc). We previously identified that botulinum toxin (BTX) injection suppresses pressure ulcer formation in a cutaneous ischemia–reperfusion injury mouse model by regulation of oxidative stress. However, the therapeutic possibility of BTX administration for preventing skin fibrosis in SSc is unclear. The objective of this study was to investigate the effect of BTX‐B on skin fibrosis in a murine model of SSc and determine the underlying mechanism. We found that BTX‐B injection significantly reduced dermal thickness and inflammatory cell infiltration in bleomycin‐induced skin fibrosis lesion in mice. We also identified that the oxidative stress signal detected through bioluminescence in OKD48 mice after bleomycin injection in the skin was significantly decreased by BTX‐B. Additionally, mRNA levels of oxidative stress associated factors (NOX2, HO‐1, Trx2) were significantly decreased by BTX‐B. Apoptotic cells in the lesional skin of bleomycin‐treated mice were significantly reduced by BTX‐B. Oxidant‐induced intracellular accumulation of reactive oxygen species in SSc fibroblasts was also inhibited by BTX‐B. In conclusion, BTX‐B might improve bleomycin‐induced skin fibrosis via the suppression of oxidative stress and inflammatory cells in the skin. BTX‐B injection may have a therapeutic effect on skin fibrosis in SSc.
Debt by design: The anatomy of a social policy fiasco – Or was it something worse?
Authors: Whiteford Peter
Published: April 2021

‘Robodebt’ is the label applied to an Australian government initiative designed to increase recoveries of ‘overpayments’ made to social security recipients. Following complaints from many of those affected, there have been multiple investigations and inquiries, and a Federal Court Case which ruled the policy unlawful. The government is in the process of paying back more than $1000 million to more than 400,000 people after conceding the largest class action settlement in Australian history, and faces calls for a Royal Commission. Robodebt resembles a ‘policy fiasco’, as the outcomes could have been foreseen at the inception of the initiative. But it differs from other examples of policy failures in that it was intentional, and not the result of mistakes in design or implementation. The initiative not only failed to achieve the Budgetary savings anticipated, it has undermined rather than protected the integrity of the social security system. It poses serious questions about the quality of Australian public administration. The objective of this article is to clarify exactly how this fiasco occurred and identify the similarities and differences between this case study and other policy failures.
Use of continuous positive airway pressure and non‐invasive ventilation for respiratory failure in an Australian aeromedical retrieval service: A retrospective case series
Authors: Weller Martin , Gibbs Clinton , Pellatt Richard , MacKillop Allan
Published: April 2021

Objective

The purpose of the present study was to investigate the use of respiratory support via continuous positive airway pressure (CPAP) and non‐invasive ventilation (NIV) in a medical retrieval service in Queensland, Australia, with reference to transport considerations and patient safety.

Methods

In this unblinded retrospective case series over a 13‐month period, a clinical database was reviewed for the use of CPAP/NIV. Retrieval metrics as well as clinical data were recorded.

Results

A total of 128 patients were transferred either by rotary (80%) or fixed wing (20%). The median transport time was 65 min. The median total mission time was 3.7 h. Fifty‐two percent of patients were female. The median age was 69 years and 93% had a background of cardiorespiratory disease. Sixty‐five percent of patients were receiving CPAP/NIV before arrival of the retrieval team. The main diagnoses were respiratory failure (29.7%), acute pulmonary oedema (26.6%) and chronic obstructive pulmonary disease (25.8%). There were no incidences of pneumothorax, intubation in transit, vomiting, desaturation, hypotension, cardiac arrest or death. In two cases NIV was abandoned due to mask intolerance and in one case there was a decrease in Glasgow Coma Scale by 2. In no cases was there a detrimental outcome for the patient.

Conclusion

The use of NIV and CPAP appears to have a low‐risk profile in aeromedical retrieval even for prolonged periods of time in an adult population.
Waterfront regeneration in Australia: Local responses to global trends in reimagining disused city docklands
Authors: Oakley Susan
Published: April 2021

This article applies ideas about critical urban assemblages to understand the planning processes, politics, and delivery of waterfront regeneration from an Australian perspective, drawing on the Port Adelaide waterfront in South Australia as a case study. Waterfront regeneration is associated with global economic deregulation, market‐led development, changes to planning regulatory requirements, and “streamlined” governance arrangements. The global spread of waterfront regeneration is an outcome of such processes, with individual waterfronts being “remade” and reimagined to reflect priorities emphasised by those forging urban policies linked to inter‐urban competitiveness and neoliberal urbanism. Waterfront developments may be categorised as “models” of success or failure that limit deeper analysis that can advance theory and practice. How such projects reflect interactions across local and global scales rather than just being expressions of global forces is a question often ignored; so, too, are those considering how policy and politics mediate those relationships. Ideas, strategies, capital, people, policy, and politics are dynamic, provisional, and contested, and are produced and assembled in particular ways to suit specific spatiotemporal contexts. On that understanding, the aim of this article is to highlight how the Port Adelaide waterfront is undergoing assembly and reassembly to reflect socioeconomic priorities and metropolitan planning agendas.
Acidosis‐induced activation of distal nephron principal cells triggers Gdf15 secretion and adaptive proliferation of intercalated cells
Authors: Cheval Lydie , Viollet Benoit , Klein Christophe , Rafael Chloé , Figueres Lucile , Devevre Estelle , Zadigue Georges , Azroyan Anie , Crambert Gilles , Vogt Bruno , Doucet Alain
Published: April 2021

Aim

Type A intercalated cells of the renal collecting duct participate in the maintenance of the acid/base balance through their capacity to adapt proton secretion to homeostatic requirements. We previously showed that increased proton secretion stems in part from the enlargement of the population of proton secreting cells in the outer medullary collecting duct through division of fully differentiated cells, and that this response is triggered by growth/differentiation factor 15. This study aimed at deciphering the mechanism of acid load‐induced secretion of Gdf15 and its mechanism of action.

Methods

We developed an original method to evaluate the proliferation of intercalated cells and applied it to genetically modified or pharmacologically treated mice under basal and acid‐loaded conditions.

Results

Gdf15 is secreted by principal cells of the collecting duct in response to the stimulation of vasopressin receptors. Vasopressin‐induced production of cAMP triggers activation of AMP‐stimulated kinases and of Na,K‐ATPase, and induction of p53 and Gdf15. Gdf15 action on intercalated cells is mediated by ErbB2 receptors, the activation of which triggers the expression of cyclin d1, of p53 and anti‐proliferative genes, and of Egr1.

Conclusion

Acidosis‐induced proliferation of intercalated cells results from a cross talk with principal cells which secrete Gdf15 in response to their stimulation by vasopressin. Thus, vasopressin is a major determinant of the collecting duct cellular homeostasis as it promotes proliferation of intercalated cells under acidosis conditions and of principal cells under normal acid‐base status.
Blueprint for pandemic response: Focus on translational medicine, clinical pharmacology and pharmacometrics
Authors: Davda Jasmine , Reynolds Kellie , Davis John D. , Smith Patrick F.
Published: April 2021

Perhaps the most important lesson learned from the COVID‐19 pandemic is that of preparedness. Enhanced surveillance systems for early threat detection will be crucial to maximizing response time for implementation of public health measures and mobilization of resources in containing an emerging pandemic. Recent outbreaks have been dominated by viral pathogens, with RNA respiratory viruses being the most likely to have pandemic potential. These should therefore be a preparedness priority. Tools in the areas of virology, drug discovery, clinical pharmacology, translational medicine and pharmacometrics should be considered key components in the rapid identification and development of existing and novel interventions for a pandemic response. Prioritization of therapeutics should be based on in vitro activity, likelihood of achieving effective drug concentrations at the site of action, and safety profile at the doses that will be required for clinical efficacy. Deployment strategies must be tailored to the epidemiology of the disease, and the adequacy of the response should be re‐evaluated in view of evolving epidemiological factors. An interdisciplinary framework integrating drug pharmacology, viral kinetics, epidemiology and health economics could help optimize the deployment strategy by improving decision‐making around who to treat, when to treat, and with what type of intervention for optimal outcomes. Lastly, while an effective vaccine will ultimately end a pandemic, antiviral drug intervention guided by clinical pharmacology principles will continue to play a critical role in any pandemic response.
Drug metabolism in severe chronic obstructive pulmonary disease: A phenotyping cocktail study
Authors: McNeill Richard P. , Zhang Mei , Epton Michael J. , Doogue Matthew P.
Published: April 2021

Aims

To evaluate the effect of severe chronic obstructive pulmonary disease (COPD) on drug metabolism by comparing the pharmacokinetics of patients with severe COPD with healthy volunteers and using the modified Inje drug cocktail.

Methods

This was a single‐centre pharmacokinetic study with 12 healthy participants and 7 participants with GOLD D COPD. Midazolam 1 mg, dextromethorphan 30 mg, losartan 25 mg, omeprazole 20 mg, caffeine 130 mg and paracetamol 1000 mg were simultaneously administered and intensive pharmacokinetic sampling was conducted over 8 hours. Drug metabolism by CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2, UGT1A6 and UGT1A9 in participants with COPD were compared with phenotypes in healthy controls.

Results

The oral clearance (95% confidence interval) in participants with COPD relative to controls was: midazolam 63% (60–67%); dextromethorphan 72% (40–103%); losartan 53% (52–55%); omeprazole 35% (31–39%); caffeine 52% (50–53%); and paracetamol 73% (72–74%). There was a 5‐fold increase in AUC for omeprazole and approximately 2‐fold increases for caffeine, losartan, dextromethorphan, and midazolam. The AUC of paracetamol, which is mostly glucuronidated, was increased by about 60%.

Conclusion

Severe COPD is associated with a clinically significant reduction in oral drug clearance. This may be greater for cytochrome P450 substrates than for glucuronidated drugs. This supports reduced starting doses when prescribing for patients with severe COPD.
Children, language and access to schools in the global South: The case of migrants in Ghana
Authors: Kyereko Daniel Owusu , Faas Daniel
Published: April 2021

Research on migrant children and young people has often focused on the global North and less on South–South migration. This article discusses language and its effect on how young migrants access Ghanaian schools. Through interviews with 68 pupils, 21 parents and 40 teachers and principals from 30 schools across Accra, we found that children and young people from francophone countries were placed in lower than age‐appropriate grades due to their lower command of English. Our study highlights the complex linguistic barriers facing migrant youth in an anglocentric educational system. The article discusses the relevance of our results in other postcolonial multilingual nations in the global South.
Congenital erythrocytosis
Authors: Mallik Nabhajit , Das Reena , Malhotra Pankaj , Sharma Prashant
Published: April 2021

Erythrocytosis, or increased red cell mass, may be labeled as primary or secondary, depending on whether the molecular defect is intrinsic to the red blood cells/their precursors or extrinsic to them, the latter being typically associated with elevated erythropoietin (EPO) levels. Inherited/congenital erythrocytosis (CE) of both primary and secondary types is increasingly recognized as the cause in many patients in whom acquired, especially neoplastic causes have been excluded. During the past two decades, the underlying molecular mechanisms of CE are increasingly getting unraveled. Gain‐in‐function mutations in the erythropoietin receptor gene were among the first to be characterized in a disorder termed primary familial and congenital polycythemia. Another set of mutations affect the components of the oxygen‐sensing pathway. Under normoxic conditions, the hypoxia‐inducible factor (HIF), upon hydroxylation by the prolyl‐4‐hydroxylase domain protein 2 (PHD2) enzyme, is degraded by the von Hippel‐Lindau protein. In hypoxic conditions, failure of prolyl hydroxylation leads to stabilization of HIF and activation of the EPO gene. CE has been found to be caused by loss‐of‐function mutations in VHL and PHD2/EGLN1 as well as gain‐of‐function mutations in HIF‐2α (EPAS1), all resulting in constitutive activation of EPO signaling. Apart from these, globin gene mutations leading to formation of high oxygen affinity hemoglobins also cause CE. Rarely, bisphosphoglycerate mutate mutations, affecting the 2,3‐bisphosphoglycerate levels, can increase the oxygen affinity of hemoglobin and cause CE. This narrative review examines the current mutational spectrum of CE and the distinctive pathogenetic mechanisms that give rise to this increasingly recognized condition in various parts of the world.
X‐ray tomography analysis of soil biopores structure under wetting and drying cycles
Authors: Cheik Sougueh , Jouquet Pascal , Maeght Jean‐Luc , Capowiez Yvan , Tran T.M. , Bottinelli Nicolas
Published: April 2021

Soil macroporosity is a highly dynamic feature driven by numerous physical and biological processes, of which bioturbation, the movement of water in soil and swelling and shrinking cycles are the main processes. To date, the interaction between these factors, especially how galleries produced by soil fauna respond to rainwater percolation and wetting–drying (WD) cycles, remains poorly known. A laboratory experiment was carried out to expose soil macrofauna galleries to three different consecutive water flow (simulated rain events of 50, 80 and 110 mm h−1 in 1 h) and drying cycles in a clayey soil. X‐ray computed tomography and image analyses were used prior to and after each exposure to assess the water stabilities of galleries and created cracks. The 3D properties (volume, diameter, specific surface area and density) of the galleries produced by termites or ants were not statistically influenced by rainwater percolation and WD cycles, suggesting a high water stability and life expectancy under natural conditions. Conversely, the crack water stability was variable and was probably influenced by the presence of galleries in the same area. This study emphasizes that the macropores created by soil fauna may persist in clayey soil and that there is a need to better understand how cracks and galleries interact.

Highlights

Evolution of soil porosity was studied by X‐ray computed tomography.

Galleries made by soil fauna were stable and resist to wetting and drying cycles.

Cracks were highly variable and were highly influenced by wetting and drying cycles.

No relationship could be evidenced between galleries and cracks.
Novel noninvasive biomarkers of prodromal Alzheimer disease: The role of optical coherence tomography and optical coherence tomography–angiography
Authors: Biscetti Leonardo , Lupidi Marco , Luchetti Elisa , Eusebi Paolo , Gujar Ramkailash , Vergaro Andrea , Cagini Carlo , Parnetti Lucilla
Published: April 2021

Background and purpose

A reduction of retinal thickness and an alteration of retinal perfusion have been found in Alzheimer disease (AD). Nowadays, retinal layers and retinal perfusion can be evaluated by means of noninvasive imaging techniques, namely, optical coherence tomography (OCT) and OCT‐angiography (OCT‐A). Here, we have compared the retinal thickness and the perfusion index, measured by means of OCT and OCT‐A, in patients with mild cognitive impairment due to AD (MCI‐AD) and in age‐ and sex‐matched cognitively healthy controls.

Methods

Twenty‐four MCI‐AD patients and 13 control subjects were enrolled. MCI‐AD patients underwent lumbar puncture; all of them showed a cerebrospinal fluid (CSF) profile compatible with AD. OCT was used for evaluating retinal volumes and thicknesses, whereas with OCT‐A we measured fractal dimension (FD), vascular perfusion density (VPD), and vessel length density (VLD) of superficial capillary plexus (SCP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and choriocapillaris. The comparisons between groups were made after adjustment for age, diabetes, and hypertension.

Results

A significant reduction of SCP‐VLD (p = 0.012), ICP‐VPD (p = 0.015), ICP‐VLD (p = 0.004), DCP‐VPD (p = 0.012), and DCP‐VLD (p = 0.009) was found in MCI‐AD patients compared to controls. Conversely, FD was higher in MCI‐AD than in controls (p = 0.044). CSF Aβ42/total tau negatively correlated with FD (r = −0.51, p = 0.010).

Conclusions

OCT‐A might have a potential role in detecting new noninvasive biomarkers for early AD detection. Retinal VPD might identify amyloid angiopathy‐related chronic injury, and FD could show early vessel recruitment as a compensative mechanism at disease onset. Further studies will be needed to confirm these findings.
Characteristics and consequences of a disease outbreak in aquatic insects
Authors: Holt Galen , Dwyer Georgia K. , Bourke Courtney , Matthews Ty G. , Macqueen Ashley , Lester Rebecca E.
Published: April 2021

Disease can be a powerful driver of population and community dynamics, as well as evolutionary processes. Disease is also emerging at increasing rates, resulting in massive impacts on populations, communities, and ecosystems. However, assessing these impacts requires foundational knowledge of disease agents and hosts, which is often lacking, particularly in aquatic insects.

We describe a recent disease outbreak in caddisflies, suggesting potential consequences for population and community dynamics of the host. We use a series of complementary studies to develop a cohesive foundation of information about this disease, including identification using genomic methods, observational prevalence studies, laboratory experiments to establish transmissibility and fitness consequences, and laboratory and field investigations to infer transmission mechanisms.

We identified the infection as being caused by the oomycete Saprolegnia—the first time this parasite has been noted in insect eggs. Prevalence surveys found high prevalence (up to 36%) with variation across space, time, and host species. We demonstrated increasing egg mortality with increasing infection within an egg mass (every 10% increase in infection rate doubles odds of mortality), thereby confirming disease. We established transmissibility and show that transmission occurs through both direct contact with infected egg masses and from background sources, which probably interact to create complex patterns of disease.

Taken together, our findings show that conditions necessary for population and community consequences are present. Specifically, increased mortality rates almost certainly occurred during the outbreak, yielding lower larval numbers and potentially altering community interactions. Transmission by contact between egg masses combined with observed species‐specific prevalence suggest shifts in the relative performance of different species because of interactions between host and parasite life histories.

Outside extreme examples such as chytrid fungus, disease has traditionally received less interest than resource competition or predation in community ecology, although disease ecology is advancing rapidly. One major hurdle is a lack of foundational knowledge characterising disease processes in natural communities, particularly in aquatic insects. Our findings highlight the importance of investigating diseases in insect eggs and provide the foundation for further investigations of how these processes play out at the population and community scale.
Development and psychometric properties of the attitude scale towards female workers in the healthcare settings
Authors: Celebi Cakiroglu Oya , Baykal Ulku
Published: April 2021

Aim

The aim of this study was to develop a new instrument to evaluate healthcare professionals’ attitudes towards female workers in the healthcare settings—the Attitude Scale Towards Female Workers (ASTFW)—and test its psychometric properties.

Design

This is a scale development study.

Method

A three‐phase structure was used: (1) creating the item pool, (2) preliminarily evaluating items and (3) refining the scale and evaluating psychometric properties. The scale's content validity, construct validity, internal consistency and temporal stability were evaluated according to the scale development guidelines. The scale's psychometric properties were tested with 1,635 healthcare professionals working in six different hospitals. The data were collected between November 2018 and July 2019.

Results

The scale items were obtained from face‐to‐face, semi‐structured, in‐depth individual interviews with the healthcare professionals. The scale's content validity index was 0.96. According to exploratory factor analysis, the scale consisted of 30 items and five subdimensions; the subdimensions were found to explain 54.48% of the total variance. Fit indices obtained with confirmatory factor analysis were at acceptable and good levels. The scale was found to have high internal consistency and temporal stability.

Conclusion

The ASTFW is a psychometrically valid and reliable measurement instrument. The 30‐item scale consists of five subdimensions: performance, gender roles, recruitment and retention, career, and emotionality.

Impact

This scale, which has good psychometric properties, can be used to perform a multidimensional evaluation of the attitudes of healthcare professionals in healthcare workplaces towards female workers. This scale can be useful in shedding light on negative attitudes towards female healthcare professionals in the health sector.
To lump, to split or to maintain? Molecular taxonomy of the spotted barb Barbodes binotatus (Cyprinidae) and closely related species in Peninsular Malaysia
Authors: Ahmad Sobri Noor Zahidah , Lavoué Sébastien , Aziz Fazimah , Mohd Nor Siti Azizah , Mohammed Akib Noor Adelyna , Khaironizam Md. Zain
Published: April 2021

The taxonomic status of the Southeast Asian spotted barb, Barbodes binotatus (Teleostei: Cyprinidae), has puzzled researchers because of large but inconsistent geographic variation of its body melanin marking pattern. In this study, the authors appraise the differentiation of B. binotatus and two closely related species, Barbodes rhombeus and saddle barb, Barbodes banksi, in Peninsular Malaysia using mitochondrial and nuclear markers. The results of this study reveal that the Peninsular Malaysia populations of each of the three species form largely reciprocal monophyletic lineages that differ from each other by a minimum of 2.3% p‐genetic distance using COI gene. Nonetheless, specimens of B. binotatus in Peninsular Malaysia are only distantly related to specimens of B. binotatus in Java (type locality). The monophyly of B. banksi is not refuted although specimens of Peninsular Malaysia are genetically distinct from those of Sarawak (type locality). The authors discuss alternative hypotheses whether each of these three valid species is a single species or each of the main five genetic lineages revealed in this study represents a distinct species. Preliminary investigations reveal a mito‐nuclear discordance at one locality in Peninsular Malaysia where B. binotatus and B. banksi co‐occur. Further studies should inform on the extent of reproductive porousness between these two lineages and others.
Live discharge from hospice for people living with dementia isn't “graduating”—It's getting expelled
Authors: Hunt Lauren J. , Harrison Krista L.
Published: April 2021

This editorial comments on the article by Luth et al. in this issue.
Requirement for oxytocin augmentation in spontaneous parturition is associated with the maternal serum steroid hormones assessed by liquid chromatography coupled to the tandem mass spectrometry
Authors: Kadivnik Mirta , Debeljak Željko , Mandić Dario , Wagner Jasenka , Kralik Kristina , Šijanović Siniša , Muller Andrijana , Šerić Vatroslav
Published: April 2021

Aim

The aim of research was to evaluate the maternal serum concentration of selected endogenous steroid hormones during spontaneous parturition at term and to determinate their association with the need for oxytocin augmentation.

Methods

Blood of 108 healthy pregnant women whose parturition started with the regular spontaneous uterine contractions was drawn at the beginning of the labor. Liquid chromatography coupled to the tandem mass spectrometry device was utilized for measurement of sex hormone binding globulin, aldosterone, androstenedione, cortisol, cortisone, corticosterone, dehydroepiandrosterone, dehydroepiandrosteron sulphate, 17‐hydroxyprogesterone, progesterone, and testosterone. Mann–Whitney U test, chi‐square test, univariate and multivariate logistic regression, and receiver operating characteristic (ROC) analysis were used for the data analysis.

Results

Reference ranges of the selected hormones assessed by liquid chromatography coupled to the tandem mass spectrometry in maternal serum were established. Statistically significant differences in the serum concentration of corticosterone, dehydroepiandrosterone, and androstenedione between mothers requiring oxytocin augmentation and the rest of women having spontaneous parturition were found (p = 0.002, p = 0.008, and p = 0.04, respectively). Concentrations were lower in the group of mothers who required oxytocin infusion for progression of labor. ROC analysis showed that all the mothers with dehydroepiandrosterone serum concentration above 21.6 nmol/L have lower chance to use oxytocin infusion for the labor progression ( area under the curve (AUC)  = 0.649, sensitivity = 71.7%, specificity = 59.6%, p = 0.006).

Conclusion

This research provided reference ranges for the selected maternal serum steroid hormones at the beginning of parturition. Association of corticosterone, dehydroepiandrosterone, and androstenedione with the need for the oxytocin infusion usage has been established. Dehydroepiandrosterone could be potential predictor of oxytocin infusion augmentation for progression of the parturition.
Extrahepatic biliary obstruction can interfere with hepatic fibrosis prediction using two‐dimensional shear wave elastography in dogs
Authors: Tamura Masahiro , Ohta Hiroshi , Osuga Tatsuyuki , Sasaki Noboru , Morishita Keitaro , Takiguchi Mitsuyoshi
Published: April 2021

Two‐dimensional shear wave elastography (2D‐SWE) can be used to quantitatively evaluate the elastic modulus of the liver as shear wave velocity (SWV), which can noninvasively predict clinically relevant hepatic fibrosis in both dogs and humans. However, extrahepatic biliary obstruction (EHBO), regardless of the presence of clinically relevant hepatic fibrosis, can influence SWVs in humans and thus may interfere with hepatic fibrosis prediction using 2D‐SWE in dogs. The aim of this prospective, observational, and one‐group pretest–posttest study is to investigate whether SWV measured by 2D‐SWE displays a difference between dogs with and without EHBO. A total of 20 dogs were included (7 with EHBO and 13 with gallbladder pathology but no EHBO) that underwent preoperative SWV measurement using 2D‐SWE. In all dogs, stages of hepatic fibrosis were evaluated histopathologically using a scoring scheme. In addition, postoperative SWVs in dogs with EHBO relieved via laparotomy were also evaluated. The median (range) SWVs in the dogs with and without EHBO were 1.91 (1.81–2.54) m/s and 1.57 (1.37–1.64) m/s, respectively. Although there was no significant difference in the histopathological hepatic fibrosis stages between the dogs with and without EHBO, the preoperative SWVs in the dogs with EHBO were significantly higher than in dogs without EHBO (P = .0004), and SWVs were found to decrease significantly after surgery (P = .0097). This study demonstrates that EHBO can increase the SWV of dogs without clinically relevant hepatic fibrosis and can interfere with the prediction of noninvasive hepatic fibrosis using 2D‐SWE.
Perception of English and Catalan vowels by English and Catalan listeners: A study of reciprocal cross-linguistic similarity
Authors: Cebrian Juli
Published: April 2021

This study reports the results of two experiments aimed at assessing the perceived similarity between English and Catalan vowels and diphthongs. Perceived similarity judgements were elicited from speakers of both languages involved and were compared to first language identification data from the same speakers. In experiment 1, a group of 27 naive Catalan listeners performed a perceptual assimilation task in which they were asked to identify Catalan and English vowels in terms of native categories and provide a goodness of fit rating. In experiment 2, a group of native speakers of Southern British English performed an adaptation of the same task. The results showed that most non-native vowels were consistently perceived as instances of a given native category, with varying degrees of goodness of fit. In a few cases, assimilation scores were very high in both experiments, pointing to the possibility of near-identical or shared categories. A few asymmetrical mappings were found, which were linked to the influence of language-specific cues such as the role of vowel duration in English. These results emphasize the importance of contrasting native and non-native perception and the potential of reciprocal approaches for making predictions about non-native perception and second language development.
Denoising click-evoked otoacoustic emission signals by optimal shrinkage
Authors: Liu Tzu-Chi , Liu Yi-Wen , Wu Hau-Tieng
Published: April 2021

Click-evoked otoacoustic emissions (CEOAEs) are clinically used as an objective way to infer whether cochlear functions are normal. However, because the sound pressure level of CEOAEs is typically much lower than the background noise, it usually takes hundreds, if not thousands, of repetitions to estimate the signal with sufficient accuracy. In this paper, we propose to improve the signal-to-noise ratio (SNR) of CEOAE signals within limited measurement time by optimal shrinkage (OS) in two different settings: covariance-based optimal shrinkage (cOS) and singular value decomposition-based optimal shrinkage (sOS). By simulation, the cOS consistently enhanced the SNR by 1–2 dB from a baseline method that is based on calculating the median. In real data, however, the cOS cannot enhance the SNR over 1 dB. The sOS achieved a SNR enhancement of 2–3 dB in simulation and demonstrated capability to enhance the SNR in real recordings. In addition, the level of enhancement increases as the baseline SNR decreases. An appealing property of OS is that it produces an estimate of all single trials. This property makes it possible to investigate CEOAE dynamics across a longer period of time when the cochlear conditions are not strictly stationary.
NAS evaluates ejecting Marcy, Ayala for sexual harassment
Authors: Wadman Meredith
Published: April 2021

First cases slowly proceeding 2 years after change in academy's bylaws allowed members to be ousted.
The Weyl side of ultracold matter
Authors: Goldman Nathan , Yefsah Tarik
Published: April 2021

Ultracold gases in optical lattices provide control and tunability for the exploration of Weyl semimetal physics
Ecological stasis on geological time scales
Authors: Roopnarine Peter D. , Banker Roxanne M. W.
Published: April 2021

Communities and functional structure persist for millions of years in a mammal fauna