bluuebunny/crossref_metadata_2025 huggingface dataset:
Bertrand’s Postulate for Carmichael Numbers
Authors: Larsen Daniel
Published: July 2022

Alford et al. [1] proved that there are infinitely many Carmichael numbers. In the same paper, they ask if a statement analogous to Bertrand’s postulate could be proven for Carmichael numbers. In this paper, we answer this question, proving the stronger statement that for all $\delta>0$ and $x$ sufficiently large in terms of $\delta $, there exist at least $e^{\frac {\log x}{(\log \log x)^{2+\delta }}}$ Carmichael numbers between $x$ and $x+\frac {x}{(\log x)^{\frac {1}{2+\delta }}}$.
Sexuality, Gender, and the Colonial Violence of Humanitarian Intervention
Authors: Vernon Patrick
Published: July 2022

Recent discussions of humanitarian intervention in international relations (IR) have often focused on the evolution of norms, and the development and contestation of the responsibility to protect (R2P) framework. While beneficial in tracing this process, most of these studies tend not to incorporate an analysis of colonialism, race, sexuality, or gender. While postcolonial studies of humanitarian intervention have done well to illustrate the relationship between humanitarian intervention and colonial violence, they still tend to neglect the study of sexuality and gender. Exploring how the sexualized, gendered, and racialized dimensions of colonialism can be incorporated into the study of humanitarian intervention, this paper proposes a queer approach. After exploring the valuable contributions of feminist scholarship, it suggests that the queer approaches of Nicola Pratt (“The Queen Boat Case in Egypt: Sexuality, National Security and State Sovereignty,” Review of International Studies 33, no. 1 [2007]: 129–44), Cynthia Weber (Queer International Relations: Sovereignty, Sexuality and the Will to Knowledge. New York, Oxford University Press, 2016), and Laura Shepherd and Laura Sjoberg (“Trans- Bodies in/of War(s): Cisprivilege and Contemporary Security Strategy,” Feminist Review 101, no. 1 [2012]: 5–23) offer some distinct contributions that build upon feminist insights. Applying these to the 2015 House of Commons debate on airstrikes against ISIL, the paper suggests that queer IR can invigorate the study of humanitarian intervention with a framework that unpacks the simultaneously gendered, sexual, and racial dimensions of colonial violence.
The Codon Statistics Database: A Database of Codon Usage Bias
Authors: Subramanian Krishnamurthy , Payne Bryan , Feyertag Felix , Alvarez-Ponce David
Published: July 2022

We present the Codon Statistics Database, an online database that contains codon usage statistics for all the species with reference or representative genomes in RefSeq (over 15,000). The user can search for any species and access two sets of tables. One set lists, for each codon, the frequency, the Relative Synonymous Codon Usage, and whether the codon is preferred. Another set of tables lists, for each gene, its GC content, Effective Number of Codons, Codon Adaptation Index, and frequency of optimal codons. Equivalent tables can be accessed for (1) all nuclear genes, (2) nuclear genes encoding ribosomal proteins, (3) mitochondrial genes, and (4) chloroplast genes (if available in the relevant assembly). The user can also search for any taxonomic group (e.g., “primates”) and obtain a table comparing all the species in the group. The database is free to access without registration at http://codonstatsdb.unr.edu.
Four cases of dermatomyositis with abnormally high anti-MDA-5 antibody titres and not high levels of serum ferritin
Authors: Umemoto Daichi , Sumitomo Shuji , Fujita Shohei , Shimizu Hayato , Oka Hideki , Kanamori Maki , Nishioka Hiroaki , Ohmura Koichiro
Published: July 2022

Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody-positive dermatomyositis is a fatal disease presenting with rapidly progressive interstitial lung disease. High ferritin levels are a well-known poor prognostic factor. A high anti-MDA-5 antibody titre was also recently identified as a poor prognostic factor. We encountered four cases that had extremely high anti-MDA-5 antibody titres without high levels of ferritin in the initial examination. All cases were female with ages ranging between 29 and 54 years (mean age, 44 years). In the initial examination, anti-MDA-5 antibody titres were 2060–3040 (normal range, <32 index), ferritin levels were 87–480 ng/ml (normal range, 2.6–129.4 ng/ml), KL-6 level was 186–1806 U/ml (normal range, <500 U/ml), and creatine kinase level was normal in all patients. One patient had respiratory distress on exertion. Computed Tomography (CT) images showed mild ground-glass attenuation/reticular shadows near the pleura in all patients. Three patients were treated with a combination of high-dose glucocorticoids, intermittent intravenous cyclophosphamide, and calcineurin inhibitors, and two required plasma exchange due to the worsening of lung lesion. In these patients, ferritin and KL-6 levels tended to elevate after the beginning of treatment. Very mild pulmonary lesions disappeared in one patient treated with moderate doses of a glucocorticoid and calcineurin inhibitor. All patients survived, and one required oxygen on exertion at discharge. The condition of patients with abnormally high anti-MDA-5 antibody titres may deteriorate even though ferritin levels were not high and lung shadows are minimal at presentation. Therefore, intensive treatment needs to be considered early in the course of the disease regardless of the serum ferritin level.
GIGANTEA Is a Negative Regulator of Abscisic Acid Transcriptional Responses and Sensitivity in Arabidopsis
Authors: Siemiatkowska Beata , Chiara Matteo , Badiger Bhaskara G , Riboni Matteo , D’Avila Francesca , Braga Daniele , Salem Mohamed Abd Allah , Martignago Damiano , Colanero Sara , Galbiati Massimo , Giavalisco Patrick , Tonelli Chiara , Juenger Thomas E , Conti Lucio
Published: July 2022

Transcriptional reprogramming plays a key role in drought stress responses, preceding the onset of morphological and physiological acclimation. The best-characterized signal regulating gene expression in response to drought is the phytohormone abscisic acid (ABA). ABA-regulated gene expression, biosynthesis and signaling are highly organized in a diurnal cycle, so that ABA-regulated physiological traits occur at the appropriate time of day. The mechanisms that underpin such diel oscillations in ABA signals are poorly characterized. Here we uncover GIGANTEA (GI) as a key gatekeeper of ABA-regulated transcriptional and physiological responses. Time-resolved gene expression profiling by RNA sequencing under different irrigation scenarios indicates that gi mutants produce an exaggerated ABA response, despite accumulating wild-type levels of ABA. Comparisons with ABA-deficient mutants confirm the role of GI in controlling ABA-regulated genes, and the analysis of leaf temperature, a read-out for transpiration, supports a role for GI in the control of ABA-regulated physiological processes. Promoter regions of GI/ABA-regulated transcripts are directly targeted by different classes of transcription factors (TFs), especially PHYTOCHROME-INTERACTING FACTOR and -BINDING FACTOR, together with GI itself. We propose a model whereby diel changes in GI control oscillations in ABA responses. Peak GI accumulation at midday contributes to establishing a phase of reduced ABA sensitivity and related physiological responses, by gating DNA binding or function of different classes of TFs that cooperate or compete with GI at target regions.
Florigen repression complexes involving rice CENTRORADIALIS2 regulate grain size
Authors: He Ying , Li Liuyu , Shi Weibiao , Tan Juhong , Luo Xixiu , Zheng Shaoyan , Chen Weiting , Li Jing , Zhuang Chuxiong , Jiang Dagang
Published: July 2022

Grain size is one of the crucial factors determining grain yield. However, the genetic and molecular mechanisms of florigen repression complexes (FRCs) underlying grain size in rice (Oryza sativa L.) have not been reported. Here, we report that the rice CENTRORADIALIS (CEN) family member OsCEN2 (also known as Rice TFL1/CEN homolog, RCN1), a phosphatidylethanolamine-binding protein (PEBP) family protein, negatively controls grain size in rice. Overexpression of OsCEN2 led to small grains, and knockout of OsCEN2 resulted in large, heavy grains. OsCEN2 influenced grain size by restricting cell expansion in the spikelet hull and seed filling. In in vivo and in vitro experiments, OsCEN2 physically interacted with a G-box factor 14-3-3 homolog, GF14f, which negatively regulates grain size. Bimolecular fluorescence complementation and yeast two-hybrid assays revealed that GF14f directly interacts with the basic leucine zipper (bZIP) transcription factor, OsFD2. Plants overexpressing OsFD2 produced smaller and lighter grains than wild-type plants. We found that OsFD2 also influences grain size by controlling cell expansion and division in the spikelet hull. Our results reveal the molecular mechanisms of the OsCEN2–GF14f–OsFD2 regulatory module in controlling grain size. Additionally, our study provides insight into the functions of the FRC in rice and suggests a strategy for improving seed size and weight.
Self-executable remedies of the Convention on International Interests in Mobile Equipment in the light of Chilean constitutional court case law on due process guarantees
Authors: Caballero Germain Guillermo
Published: July 2022

The purpose of this work is to analyze whether the Constitutional Court decisions on due process as applied to the realization of security interests may hinder an eventual ratification of the Cape Town Convention and its protocols.
Association of hepatitis C virus genotype 2 spread with historic slave trade and commerce routes in Western Africa
Authors: Postigo-Hidalgo Ignacio , Magassouba N’Faly , Soropogui Barré , Fichet-Calvet Elisabeth , Drexler Jan Felix
Published: July 2022

The hepatitis C virus genotype 2 (HCV2) is endemic in Western and Central Africa. The HCV2 evolutionary origins remain uncertain due to the paucity of available genomes from African settings. In this study, we investigated the molecular epidemiology of HCV infections in rural Guinea, Western Africa, during 2004 and 2014. Broadly reactive nested reverse transcription polymerase chain reaction (RT-PCR)-based screening of sera from 1,571 asymptomatic adults resulted in the detection of 25 (1.5 per cent; 95 per cent confidence interval 0.9–2.3) positive samples, with a median viral load of 2.54E + 05 IU/ml (interquartile range 6.72E + 05). HCV-infected persons had a median age of 47 years, and 62.5 per cent were male and 37.5 per cent were female. The full polyprotein-encoding genes were retrieved by a combination of high throughput and Sanger sequencing from 17 samples showing sufficiently high viral loads. Phylogenetic analysis and sequence distances ≥13 per cent averaged over the polyprotein genes compared to other HCV2 subtypes revealed nine previously unknown HCV2 subtypes. The time to the most recent common ancestor of the Guinean HCV2 strains inferred in a Bayesian framework was 493 years (95 per cent Highest posterior density (HPD) 453–532). Most of the Guinean strains clustered poorly by location on both the level of sampling sites within Guinea and the level of countries in the phylogenetic reconstructions. Ancestral state reconstruction provided decisive support (Bayes factor > 100) for an origin of HCV2 in Western Africa. Phylogeographic reconstructions in a Bayesian framework pointed to a radial diffusion of HCV2 from Western African regions encompassing today’s countries like Ghana, Guinea Bissau, or Burkina Faso, to Central and Northern African regions that took place from the 16th century onwards. The spread of HCV2 coincided in time and space with the main historic slave trade and commerce routes, supported by Bayesian tip-association significance testing (P = 0.01). Our study confirms the evolutionary origins of HCV2 in Western Africa and provides a potential link between historic human movements and HCV2 dispersion.
Variation in Bed-to-Physician Ratios During Weekday Daytime Hours in ICUs in Australia and New Zealand*
Authors: Wunsch Hannah , Pilcher David V. , Litton Edward , Anstey Matthew , Garland Allan , Gershengorn Hayley B.
Published: July 2022

OBJECTIVES:

To determine common “bed-to-physician” ratios during weekday hours across ICUs and assess factors associated with variability in this ratio.

DESIGN:

Retrospective cohort study.

SETTING:

All ICUs in Australia/New Zealand that participated in a staffing survey administered in 2017–2018.

PATIENTS:

ICU admissions from 2016 to 2018.

METHODS:

We linked survey data with patient-level data. We defined: 1) bed-to-intensivist ratio as the number of usually available ICU beds divided by the number of onsite weekday daytime intensivists; and 2) bed-to-physician ratio as the number of available ICU beds divided by the total number of physicians (intensivists + nonintensivists, including trainees). We calculated the median and interquartile range (IQR) of bed-to-intensivist ratio and bed-to-physician ratios during weekday hours. We assessed variability in each by type of hospital and ICU and by severity of illness of patients, defined by the predicted hospital mortality.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of the 123 (87.2%) of Australia/New Zealand ICUs that returned staffing surveys, 114 (92.7%) had an intensivist present during weekday daytime hours, and 116 (94.3%) reported at least one nonintensivist physician. The median bed-to-intensivist ratio was 8.0 (IQR, 6.0–11.4), which decreased to a bed-to-physician ratio of 3.0 (IQR, 2.2–4.9). These ratios varied with mean severity of illness of the patients in the unit. The median bed-to-intensivist ratio was highest (13.5) for ICUs with a mean predicted mortality > 2–4%, and the median bed-to-physician ratio was highest (5.7) for ICUs with a mean predicted mortality of > 4–6%. Both ratios decreased and plateaued in ICUs with a mean predicted mortality for patients greater than 8% (median bed-to-intensivist ratio range, 6.8–8.0, and bed-to-physician ratio range of 2.4–2.7).

CONCLUSIONS:

Weekday bed-to-physician ratios in Australia/New Zealand ICUs are lower than the bed-to-intensivist ratios and have a relatively fixed ratio of less than 3 for units taking care of patients with a higher average severity of illness. These relationships may be different in other countries or healthcare systems.
Is the Technology Era Aging You? A Review of the Physiologic and Psychologic Toll of Technology Use
Authors: McKesey Jacqueline , Fabi Sabrina G.
Published: July 2022

BACKGROUND

Technology use is at an all-time high and its potential impact on psychological and physiologic health should be explored.

OBJECTIVE

The objective of this narrative review was to identify the role of technology use on health and well-being.

MATERIALS AND METHODS

Authors performed a review of PubMed and publications of the World Health Organization, Department of Defense, and Centers for Disease Control and Prevention to determine the impact of technology regarding electromagnetic radiation (EM), posture and mobility, sleep disturbance, and psychological stress and well-being.

RESULTS

Studies on the impact of EM were conflicting, with about 45% reporting negative consequences and 55% reporting no effect. Radiofrequency EM (RF-EM) may more significantly affect fibroblasts and immature cells. Device use was implicated in worsening cognitive focus, imbalance, and sleep. Social media use affects self-esteem and mental health and is associated with up to 33% presence of addiction. Effects seem to be dose related and more pronounced in younger ages.

CONCLUSION

Technology use significantly affects sleep, mental health, and cognitive function. Seeking psychological help, limiting social media use, and reducing use before sleep may partially mitigate these effects. The impact of EM is undetermined, but the WHO lists RF-EM as a potential carcinogen.
Ten-Year Institutional Experience to Predict Risk of Calvarial Bone Flap Loss Using Long-Term Outcome Data
Authors: Wu Shannon S. , Specht Brandon C. , Kwiecien Grzegorz J. , Aliotta Rachel E. , Mohammadi Alireza M. , Gastman Brian
Published: July 2022

Background:

Calvarial bone flap (CBF) loss is a common complication following craniotomy and subsequent skull reconstruction can be challenging. Defining predictors of CBF failure not only improves patient outcomes but reduces the need for complex reconstruction often requiring plastic surgery consultation. As CBF failure can occur many years following craniotomy, this study aimed to determine risk factors of CBF loss using long-term follow-up.

Materials and Methods:

This retrospective study included patients who underwent craniotomy with CBF reinsertion between 2003 and 2013 at a tertiary academic institution. Patients were included if demographics, comorbidities, and long-term outcomes were available. Multivariable logistic regression modeled the odds of CBF failure, defined as permanent removal for bone flap-related issues. The median follow-up was 6.9 years (interquartile range: 1.8–10.8 y).

Results:

There were 222 patients who met inclusion criteria and underwent craniotomy with CBF reinsertion, primarily for tumor resection or intracranial pressure relief. CBF failure occurred in 76 (34.2%) patients. Up to 4 CBF reinsertions were performed in both failure and nonfailure groups. The risks of CBF loss increased with each additional CBF elevation by 17-fold (P<0.001), male sex by 3-fold (P=0.005), and tumor etiology by 3-fold (P=0.033) (C-index=0.942).

Conclusions:

Each CBF reinsertion dramatically increases the risk of CBF loss. This finding may optimize patient selection and surgical planning. Early multidisciplinary discussions between plastic surgeons and neurosurgeons may avoid multiple CBF elevations and prevent the adverse sequela of high-risk calvarial reconstruction efforts.
An information sign changes the way the public perceives exotic pond sliders Trachemys scripta in the Altrhein of Kehl (Germany)
Authors: Schradin Carsten
Published: July 2022

Invasive pond sliders (Trachemys scripta) have been released in thousands of freshwaters within Europe and reproduce in the southern states and even in warm areas of Germany. All member states of the European Union must have an action plan how to fight this invasive species. The German action plan focusses on informing the public, but to date no study investigated the impact of such actions. Instead, NGOs setting up information signs report that this does not stop the release of exotic pond turtles, but without any quantitative measure. In 2019, we put up an information sign at the Althrein of Kehl, an oxbow lake where for the first time it had been shown that T. scripta is breeding in Germany. I performed interviews with people walking along the oxbow lake before the sign was pit up in 2019, and again in 2022. Counts of exotic pond turtles still increased, but this was mainly due to an increased number of small pond turtles, while numbers of very large ones did not further increase. This indicates that the increase in peak counts might be rather due to local reproduction than additional release. After the information sign was set up, more people responded that the presence of exotic pond turtles is problematic for nature conservation and animal welfare, that it’s illegal to release them, and that they should be removed. This response was especially strong in people who had read the information sign. Independent of the information sign, most interviewed people stated that one should not release pond turtles into the wild, but bring them to animal shelters. While the data here only represent one single case study that might not be representative, it’s the first study showing that putting up information signs is effective in changing the attitude of people who had read it. This indicates that investment into informing the public is worthwhile, but also that at the same time evaluations of the impact of the measures are important. National action plans should focus on a combination of informing the public and removing the exotic pond turtles, but also on providing keepers of these animals the option to leave the animals at an animal shelter instead of releasing them into the wild.
Evasion of neutralizing antibodies by Omicron sublineage BA.2.75
Authors: Sheward Daniel J. , Kim Changil , Fischbach Julian , Muschiol Sandra , Ehling Roy A. , Björkström Niklas K. , Karlsson Hedestam Gunilla B. , Reddy Sai T. , Albert Jan , Peacock Thomas P. , Murrell Ben
Published: July 2022

An emerging SARS-CoV-2 Omicron sublineage, BA.2.75, is increasing in frequency in India and has been detected in at least 15 countries as of 19 July 2022. Relative to BA.2, BA.2.75 carries nine additional mutations in spike. Here we report the sensitivity of the BA.2.75 spike to neutralization by a panel of clinically-relevant and pre-clinical monoclonal antibodies, as well as by serum from blood donated in Stockholm, Sweden, before and after the BA.1/BA.2 infection wave.

BA.2.75 largely maintains sensitivity to bebtelovimab, despite a slight reduction in potency, and exhibits moderate susceptibility to tixagevimab and cilgavimab. For sera sampled both before and after the BA.1/BA.2 infection wave, BA.2.75 does not show significantly greater antibody evasion than the currently-dominating BA.5.
Assessment of somatosensory and cognitive-motor processing time in retired athletes with a history of repeated head trauma
Authors: Pearce Alan J. , King Doug , Kidgell Dawson J , Frazer Ashlyn K , Tommerdahl Mark , Suter Catherine M
Published: July 2022

Measurement of the adverse outcomes of repeated head trauma in contact sport athletes is often achieved using tests where the comparator is the ‘score’ or the ‘accuracy’ obtained. While it is expected that ex-athletes would perform worse than controls, previous studies have shown inconsistent results. Here we have attempted to address these inconsistencies from a different perspective by quantifying not only accuracy, but also the time of motor responses (response time). We tested age-matched control subjects who have never experienced head trauma (n=20; 41.8 ± 14.4 years), and two cohorts of retired contact sport athletes with a history of head trauma and concussions; one with self-reported concerns (n=36; 45.4 ± 12.6 years), and another with no ongoing concerns (n=19; 43.1 ± 13.5 years). Participants performed cognitive (Cogstate) and somatosensory (Cortical Metrics) testing and both accuracy and response time were recorded. Transcranial magnetic stimulation (TMS) was undertaken to investigate corticospinal conduction and excitability. Results showed that in both test batteries there was little difference between groups when considering only accuracy scores. By contrast, response times in all but one test revealed that ex-athletes with self-reported concerns were significantly slower compared to no concern ex-athlete or control groups (p ranges 0.031 to <0.001). TMS latency showed significantly increased conduction time (p=0.008) in the group with ongoing concerns. These findings suggest that incorporating response times in cognitive and somatosensory testing is more informative than considering accuracy scores alone when assessing cognitive processing ability in retired contact sport athletes with ongoing brain health concerns.
KAI2-KL signalling regulates root hair elongation under magnesium deficiency by activating auxin, ethylene, and nitric oxide biosynthesis and signalling genes
Authors: Shah Faheem Afzal , Ni Jun , Chen Xue , Tang Caiguo , Wu Lifang
Published: July 2022

Root hair elongation (RHL), which expands the absorptive surface area of the root, is a crucial adaptation in plants for survival under magnesium (Mg) deficient soil. Despite the significance of this trait, the molecular mechanism in Mg starvation regulating RHL is elusive. We demonstrated that karrikins regulate RHL under a limited supply of Mg via crosstalk with auxin, ethylene, and NO. We used KAI2-KL-signalling mutants, auxin, ethylene, and NO-related genes mutants Arabidopsis and pharmacological method to investigate the role of KAI2-KL-signalling, and its interaction with ethylene, auxin, and NO in the process of RHL in Mg deficient conditions. Mg deficiency could not enhance RHL in KAI2-KL-signalling mutants such as kai2 and max2 Arabidopsis. Interestingly, exogenous application of ethylene, nitric oxide, or auxin recovered RHL of kai2 and max2 Arabidopsis under Mg deficiency. In contrast, exogenous supplementation of KAR1 could not rescue RHL in auxin, ethylene, and NO-related mutants Arabidopsis. In conclusion, we suggest that karrikins signalling might regulate the RHL in response to low Mg by acting as an upstream signalling pathway of auxin, ethylene, and NO signalling.
Requirement of sequential hydrolysis by CD73 and ALP for uptake of vitamin B2 into cells
Authors: Shichinohe Natsuki , Kobayashi Daisuke , Izumi Ayaka , Hatanaka Kazuya , Fujita Rio , Kinoshita Taroh , Inoue Norimitsu , Hamaue Naoya , Wada Keiji , Murakami Yoshiko
Published: July 2022

Extracellular hydrolysis of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) to riboflavin is thought to be important for cellular uptake of vitamin B2 because FAD and FMN are hydrophilic and do not pass the plasma membrane. However, it is not clear whether FAD and FMN are hydrolyzed by cell surface enzymes for vitamin B2 uptake. Here, we show that in human cells, FAD, a major form of vitamin B2 in plasma, is hydrolyzed by CD73 (also called ecto-5′ nucleotidase) to FMN, then FMN is hydrolyzed by alkaline phosphatase to riboflavin, which is efficiently imported into cells. This process is impaired on the surface of glycosylphosphatidylinositol (GPI)-deficient cells due to lack of these GPI-anchored enzymes. During culture of GPI-deficient cells with FAD or FMN, hydrolysis of these forms of vitamin B2, intracellular levels of vitamin B2, vitamin B2-dependent pyridoxal 5′-phosphate formation, and mitochondrial functions were significantly decreased compared with those in GPI-restored cells. These results suggest that inefficient uptake of vitamin B2 might account for mitochondrial dysfunction seen in some cases of inherited GPI deficiency.
Temporal interference current stimulation in peripheral nerves
Authors: Budde Ryan B. , Williams Michael T. , Irazoqui Pedro P.
Published: July 2022

One strategy to electrically stimulate nerves utilizes the interference of multiple high frequency waveforms. This technique has recently gained significant attention as a method to improve the state-of-the-art in neurostimulation. Here we report our investigation into the fundamental properties of the neuronal response to these types of waveforms. Our data suggest, contrary to the currently accepted explanation, that neurons do not extract envelopes at all, and that the response to these signals is well explained by a resistor-capacitor (i.e., integrator) membrane with a fixed firing threshold. This new understanding of the fundamental mechanism of interferential neural stimulation changes how we should model and evaluate the safety and efficacy of these signals. Utilizing this new understanding, we develop several novel interferential stimulation techniques. Interferential strategies demonstrate promising results and may improve many neuromodulation therapies.
Cell envelope remodeling requires high concentrations of biotin during Mycobacterium abscessus model lung infection
Authors: Sullivan Mark R. , McGowen Kerry , Liu Qiang , Akusobi Chidiebere , Young David C. , Mayfield Jacob A. , Raman Sahadevan , Wolf Ian D. , Moody D. Branch , Aldrich Courtney C. , Muir Alexander , Rubin Eric J.
Published: July 2022

Mycobacterium abscessus is an emerging pathogen resistant to most frontline antibiotics. M. abscessus causes lung infection, predominantly in patients with lung disease or structural abnormalities. To interrogate mechanisms required for M. abscessus survival in the lung, we developed a lung infection model using air-liquid interface culture and performed a screen to identify differentially required genes. In the lung model, synthesis of the cofactor biotin is required due to increased intracellular biotin demand, and pharmacological inhibition of biotin synthesis halts M. abscessus proliferation. Increased quantities of biotin are required to sustain fatty acid remodeling that serves to increase cell envelope fluidity, which in turn promotes M. abscessus survival in the alkaline lung environment. Together, these results indicate that biotin-dependent fatty acid remodeling plays a critical role in pathogenic adaptation to the lung niche and suggests that biotin synthesis and fatty acid metabolism are therapeutic targets for treatment of M. abscessus infection.
The dual role of a multi-heme cytochrome in methanogenesis: MmcA is important for energy conservation and carbon metabolism in Methanosarcina acetivorans
Authors: Downing Blake E. , Gupta Dinesh , Nayak Dipti D.
Published: July 2022

Methanogenic archaea belonging to the Order Methanosarcinales conserve energy using an electron transport chain (ETC). In the genetically tractable strain Methanosarcina acetivorans, ferredoxin donates electrons to the ETC via the Rnf (Rhodobacter nitrogen fixation) complex. The Rnf complex in M. acetivorans, unlike its counterpart in Bacteria, contains a multiheme c-type cytochrome (MHC) subunit called MmcA. Early studies hypothesized MmcA is a critical component of Rnf, however recent work posits that the primary role of MmcA is facilitating extracellular electron transport. To explore the physiological role of MmcA, we characterized M. acetivorans mutants lacking either the entire Rnf complex (Δrnf) or just the MmcA subunit (ΔmmcA). Our data show that MmcA is essential for growth during acetoclastic methanogenesis but neither Rnf nor MmcA are required for methanogenic growth on methylated compounds. On methylated compounds, the absence of MmcA alone leads to a more severe growth defect compared to a Rnf deletion likely due to different strategies for ferredoxin regeneration that arise in each strain. Transcriptomic data suggest that the ΔmmcA mutant might regenerate ferredoxin by upregulating the cytosolic Wood-Ljundahl pathway for acetyl-CoA synthesis, whereas the Δrnf mutant may repurpose the F420 dehydrogenase complex (Fpo) to regenerate ferredoxin coupled to proton translocation. Beyond energy conservation, the deletion of Rnf or MmcA leads to some shared and some unique transcriptional changes in methyltransferase genes and regulatory proteins. Overall, our study provides systems-level insights into the non-overlapping roles of the Rnf bioenergetic complex and the associated MHC, MmcA.

Importance

Methane is a greenhouse gas that is ten times more potent than carbon dioxide and efforts to curb emissions are crucial to meet climate goals. Methane emissions primarily stem from the metabolic activity of microorganisms called methanogenic archaea (methanogens). The electron transport chain (ETC) in methanogens that belong to the Order Methanosarcinales has been the focus of many in vitro studies to date, but the endogenous functions of the bioenergetic complexes that comprise the ETC have rarely been investigated. In this study, we use genetic techniques to functionally characterize the Rnf bioenergetic complex and the associated multi-heme c-type cytochrome MmcA in the model methanogen, Methanosarcina acetivorans. Our results show that MmcA and Rnf have shared and unique roles in the cell, and that, contrary to current knowledge, M. acetivorans has the capacity to induce at least two alternative pathways for ferredoxin regeneration in the absence of a functional Rnf complex.
AXEAP: a software package for X-ray emission data analysis using unsupervised machine learning
Authors: Hwang In-Hui , Solovyev Mikhail A. , Han Sang-Wook , Chan Maria K. Y. , Hammonds John P. , Heald Steve M. , Kelly Shelly D. , Schwarz Nicholas , Zhang Xiaoyi , Sun Cheng-Jun
Published: July 2022

The Argonne X-ray Emission Analysis Package (AXEAP) has been developed to calibrate and process X-ray emission spectroscopy (XES) data collected with a two-dimensional (2D) position-sensitive detector. AXEAP is designed to convert a 2D XES image into an XES spectrum in real time using both calculations and unsupervised machine learning. AXEAP is capable of making this transformation at a rate similar to data collection, allowing real-time comparisons during data collection, reducing the amount of data stored from gigabyte-sized image files to kilobyte-sized text files. With a user-friendly interface, AXEAP includes data processing for non-resonant and resonant XES images from multiple edges and elements. AXEAP is written in MATLAB and can run on common operating systems, including Linux, Windows, and MacOS.
How did fire and rescue services (and HMICFRS) in England respond to the COVID-19 pandemic?
Authors: Murphy Peter , Lakoma Katarzyna
Published: July 2022

Purpose

This paper explores how fire and rescue services in England responded to the challenges and opportunities presented by the COVID-19 pandemic. It examines the form and nature of fire and rescue services’ collaborations with the ambulance, police and other services and how effective their emergency planning arrangements prepared them for the pandemic.

Design/methodology/approach

The authors briefly set out the background to the emergency services response to recent events of national significance in the UK and North America, focussing on the collaborative aspects of the emergency services response. The authors then examine three sets of secondary sources, namely documents specifically related to Fire and Rescue Services’ response to the COVID-19 pandemic in the UK.

Findings

All three investigations found that the pandemic had provided an opportunity for issues relating to planning and collaboration to be re-examined and for the emergence of new innovations (both technological and organisational) to provide new responses and solutions. Although the Inspectorate found that the services had generally responded well, it controversially criticised the role of the Fire Brigades Union in the national and local response to the pandemic.

Research limitations/implications

The research is situationally bound to England although there may be transferable lessons to other services and jurisdictions.

Practical implications

Potential future improvements are identified at national and local levels for policy and for the operational response to widespread and long-term emergencies.

Originality/value

England has had very few contemporary public health emergencies on the scale of the COVID-19 pandemic; this research presents an important opportunity for seeking to understand what is working well and where improvements are required to improve both the local and national response in relation to such a complex and dynamic environment.
What role can education play in integrated care? Lessons from the ECHO (Extensions for Community Health Outcomes) Concussion program
Authors: Zhao Q. Jane , Cupido Nathan , Whitehead Cynthia R. , Mylopoulos Maria
Published: July 2022

Purpose

Design, implementation, and evaluation are all important for integrated care. However, they miss one critical factor: education. The authors define “integrated care education” as meaningful learning that purposefully supports collaboration and the development of adaptive expertise in integrated care. The ECHO (Extensions for Community Health Outcomes) model is a novel digital health solution that uses technology-enabled learning (TEL) to facilitate, support, and model integrated care education. Using ECHO Concussion as a case study, the authors describe the effects of technology-enabled integrated care education on the micro-, meso-, and macro-dimensions of integrated care.

Design/methodology/approach

This case study was constructed using data extracted from ECHO Concussion from video-archived sessions, participant observation, and internal program evaluation memos. The research team met regularly to discuss the development of relevant themes to the dimensions of integrated care.

Findings

On the micro-level, clinical integration occurs through case-based learning and the development of adaptive expertise. On the meso-level, professional integration is achieved through the development of the “specialist generalist,” professional networks and empathy. Finally, on the macro-level, ECHO Concussion and the ECHO model achieve vertical and horizontal system integration in the delivery of integrated care. Vertical integration is achieved through ECHO by educating and connecting providers across sectors from primary to quaternary levels of care. Horizontal integration is achieved through the establishment of lateral peer-based networks across sectors as a result of participation in ECHO sessions with a focus on population-level health.

Originality/value

This case study examines the role of education in the delivery of integrated care through one program, ECHO Concussion. Using the three dimensions of integrated care on the micro-, meso-, and macro-levels, this case study is the first explicit operationalization of ECHO as a means of delivering integrated care education and supporting integrated care delivery.
Reflections and predictions on effects of COVID-19 pandemic on retailing
Authors: Verhoef Peter C. , Noordhoff Corine S. , Sloot Laurens
Published: July 2022

Purpose

The Covid-19 pandemic has a strong effect on societies, business and consumers. Governments have taken measures to reduce the spread of the pandemic, such as social distancing and lockdowns. The latter has also resulted in a temporary closure of physical stores for “non-essential” retailing. Covid-19 thus has a profound impact on how people live. The period of relative isolation, social distancing and economic uncertainty changes the way we behave. New consumer behaviors span all areas of life, from how we work to how we shop to how we entertain ourselves. These shifts have important implications for retailers. This paper aims to discuss the potential structural effect on shopping behavior and retailing when Covid-19 measures are no longer needed and society moves back to a normal situation.

Design/methodology/approach

The paper synthesizes empirical and conceptual literature on the consequences of COVID-19 and introduces a conceptual framework along with a set of predictions that can be investigated with empirical data.

Findings

This study suggests that Covid-19 shapes both consumer needs and behavior and how retailers respond to these changes. Moreover, it suggests that this will not only affect market outcomes (i.e. retail sales and market share online) but also firm outcomes (i.e. customer experience, firm sales) and importantly the competition between online and offline retailers.

Originality/value

In the conceptual framework, this study aims to advance knowledge on longer-term outcomes (vs immediate outcomes such as panic buying) and how COVID-19 is changing the competitive landscape of retail.
Seismic data augmentation for automatic fault picking using deep learning
Authors: Pham Nam , Fomel Sergey
Published: July 2022

We propose a method to generate seismic images with corresponding fault labels for augmenting training data in automatic fault detection. Our method is based on two generative adversarial networks: one for creating a fault system and the other for generating two‐dimensional seismic images with faults as a condition. Our method can capture the characteristics of field seismic data during inference to generate samples that have properties of both field seismic data and synthetic training data. We then use the newly generated seismic images with corresponding fault labels to train a convolutional neural network for fault picking. We test the proposed approach on a three‐dimensional field dataset from the Gulf of Mexico. We use different areas in the field dataset as input to generate new training data for corresponding fault‐picking models. The results show that the generated training data from our method help in improving the fault‐picking models in the targeted areas.
The impact of regional trade policy uncertainty on the productivity of Chinese export enterprises: The case of China–ASEAN Free Trade Area
Authors: Zhou Kexuan , Yu Linhui , Jiang Xinlin , Kumar Sanjay
Published: July 2022

Reduction of regional trade policy uncertainty is critical for promoting Chinese export enterprise productivity and will help the economy enter the high‐quality development stage. We use the case of the China–ASEAN Free Trade Area to empirically tests the impact of the reduction of regional trade policy uncertainty on the productivity of Chinese export enterprises. We apply the difference‐in‐difference method to micro‐enterprise level data from the “China industrial enterprise database” and “China Customs enterprise database” for 2007–2013. Our analysis and results show that establishing the China–ASEAN Free Trade Area has dramatically reduced regional trade policy uncertainty, significantly impacting the productivity of Chinese enterprises exporting to ASEAN. The results also show that enterprises with different ownership types, regions, factor density, and pollution emission intensity show significant heterogeneity in the level of productivity improvement. Applying a mechanism test, we found that the promotion of productivity from a reduction of regional trade policy uncertainty is achieved through the learning effect, the competition effect, and improving the trade environment of imported intermediate goods. The learning effect mechanism has the highest contribution, accounting for 39.01% of the net effect. The empirical results provide novel insight into promoting the productivity of Chinese enterprises exporting to ASEAN from the perspective of reducing regional trade policy uncertainty.
Roof‐dependent atrial flutter with epicardial conduction pathway masked by left atrium posterior wall debulking ablation
Authors: Ishimura Masayuki , Yamamoto Kayo , Yamamoto Masashi , Himi Toshiharu , Kobayashi Yoshio
Published: July 2022

Roof‐dependent atrial flutter (AFL) is a major tachyarrhythmia rotating in the left atrium (LA). Here, we describe a case of roof‐dependent AFL during atrial fibrillation ablation. LA posterior wall (LAPW) debulking ablation was performed before the induction. Atrial tachycardia (AT) was induced by burst pacing, and the 3D mappings showed a focal pattern from the LA inferior area. The post‐pacing interval from the roof and bottom line corresponded to the AT cycle length. The LAPW debulking ablation masked roof‐dependent AFL due to the lack of endocardium potentials in the LAPW. We report that roof‐dependent AFL connected by epicardium fibers.
The costs of ideological prosociality: Analyses of the EuropeanSocialSurvey from 2002 to 2018 find negative relationships between endorsing universalistic values and well‐being and social capital
Authors: Nezlek John B.
Published: July 2022

Traditionally, prosociality has been conceptualized in terms of the interpersonal domain, for example, helping behavior. Nevertheless, people can be prosocial in terms of ideological domains, for example, social policies they support. The present study examined the utility of distinguishing interpersonal and ideological prosocial values as predictors of well‐being and social capital. Data from nine European Social Surveys were combined. TheUniversalismandBenevolencevalues of Schwartz's basic human values were treated as measures of ideological and interpersonal prosocial values. Relationships betweenUniversalismandBenevolenceand well‐being and social capital were examined with multilevel models, persons nested with rounds, rounds nested within countries. Respondent sex, age, and education were included as covariates. These analyses found thatBenevolencewas positively related to satisfaction with life and happiness, whereasUniversalismwas negatively related to satisfaction with life and happiness. Although endorsing both values was positively related to attitudinal measures of social capital (e.g., people can be trusted),Universalismwas negatively related to self‐reports of social activity, whereasBenevolencewas either positively related or unrelated to self‐reports of social activity. Being ideologically prosocial appears to be associated with reduced well‐being. Future research is needed to explain the mechanisms responsible for this relationship.
Changes in flourishing from adolescence to young adulthood: An 8‐year follow‐up
Authors: Palmer Ashley N. , Patel Mansi , Narendorf Sarah C. , Sledge Shellye , Sanchez Katherine
Published: July 2022

Most research on mental health among adolescents and young adults concentrates on understanding mental illness. However, mental health is more than the absence of mental illness. Among adolescents and young adults, positive mental health—a combination of emotional, social and psychological well‐being—is related to higher prosocial behaviour, school integration and self‐concept. However, much of the research on positive mental health among young adults has been with college students. Limited research has examined the presence and correlates of positive mental health, or flourishing, among a nationally representative sample of US young adults. This study extended from another researcher's original examination of positive mental health among US adolescents to describe the prevalence of flourishing among these same individuals in young adulthood. Our sample included 1090 individuals from the 2011 Panel Study of Income Dynamics Transition into Adulthood Supplement. Univariate and bivariate tests were used to describe the prevalence of flourishing during young adulthood and changes from adolescence to young adulthood. We used multivariable logistic regression to examine the relationships among indicators of healthy development and flourishing. Results suggest that flourishing improved during the transition into young adulthood and that targeting factors like life skills and civic engagement may enhance flourishing.
Opposite roles of Kindlin orthologs in cell survival and proliferation
Authors: Zhevlakova Irina , Xiong Luyang , Liu Huan , Dudiki Tejasvi , Ciocea Alieta , Podrez Eugene , Byzova Tatiana V.
Published: July 2022

Objective

It is unclear why adhesion‐dependent cells such as epithelium undergo anoikis without anchorage, while adhesion‐independent blood cells thrive in suspension. The adhesive machinery of these cells is similar, with the exception of Kindlin orthologs, Kindlin 2 (K2) and Kindlin 3 (K3). Here we address how Kindlins control cell survival and proliferation in anchorage‐dependent and independent cells.

Material and Methods

To demonstrate the opposite roles of Kindlin's in cell survival we utilized in vivo and in vitro models and K3 and K2 knockdown and knockin cells. We used human lymphocytes from the K3 deficient patients in tumour model, K3 knockout and knockin macrophages and K2 knockout and knockin MEF cells for experiments in under conditions of adhesion and in suspension.

Results

Depletion of K3 promotes cell proliferation and survival of anchorage‐independent cells regardless of cell attachment. In contrast, the absence of K2 in anchorage‐dependent cells accelerates apoptosis and limits proliferation. K3 deficiency promotes human lymphoma growth and survival in vivo. Kindlins' interaction with paxillin, is critical for their differential roles in cell anchorage. While disruption of K2‐paxillin binding leads to increased apoptosis, the lack of K3‐paxillin binding has an opposite effect in adhesion‐independent cells.

Conclusion

Kindlin ortologs and their interaction to cytoskeletal protein paxillin define the mechanisms of anchorage dependence. Our study identifies the key elements of the cell adhesion machinery in cell survival and tumour metastasis, proposing possible targets for tumour treatment.