bluuebunny/crossref_metadata_2025 huggingface dataset:
The reproduction of canonical silences: re-reading Habermas in the context of slavery and the slave trade
Authors: Willems Wendy
Published: December 2022

Recent discussions on “decolonizing” knowledge production have often foregrounded the importance of centering “marginal” perspectives, which is crucial but insufficient as it risks leaving the canon untouched. Jürgen Habermas’ book on the bourgeois public sphere is one of the most frequently cited and debated canonical texts in media and communication studies. Drawing on the case of London’s coffee houses and newspapers, this article argues for a critical re-engagement with canonical thinkers. It examines what the emergence of a bourgeois public sphere in 17th- and 18th-century England looks like if we re-read it within the context of slavery and the slave trade. The article demonstrates that race does not simply provide another “prism” to examine the bourgeois public sphere but instead enables and is constitutive of it. The reproduction of canonical silences through the continued circulation of influential texts has implications for how we conceptualize racialized publics in contemporary times.
Quantification of Remimazolam Besylate (CNS7056B) and Its Metabolite (CNS7054X) by LC–MS/MS in Human Plasma Using Midazolam-d4 Maleate as Internal Standard
Authors: Schmidt Stefanie , Krajinovic Ljubica , Mertens Christian , Schramm Lisa , Schüttler Jürgen , Fechner Jörg
Published: December 2022

A new assay was developed to measure the concentration of remimazolam besylate (CNS7056B) and its major carboxylic acid metabolite (CNS7054X) in human plasma. For this new assay method, midazolam-d4 maleate was used as an internal standard. After setting up a previously described assay method, using CNS7056-d4 and CNS7054-d4 as internal standards, analytical results of both methods were compared. For the new analytical method, ultra-high-performance liquid chromatography (UHPLC) with tandem mass spectrometry was applied. A purification method, using solid phase extraction, was developed and validated. The chromatographic separation of the analytes was achieved with a mobile phase gradient using a Water Acquity™ UHPLC-System. The Kinetex™ biphenyl 50 × 2.1 mm UHPLC column was used with a particle diameter of 1.7 μm (Phenomenex, Germany). A measuring range of 0.6–2,000 ng/mL for CNS7056B and of 6–20,000 ng/mL for CNS7054X could be achieved with this new assay. The lower limit of quantification was 0.6 ng/mL for CNS7056B and 6 ng/mL for CNS7054X. The assay was validated according to US Food and Drug Administration guidelines. The new method showed an accuracy of 96.9–110.4% and a precision of 2.1–6.7% for both analytes.
Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019: The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study
Authors: Mukae Hiroshi , Yotsuyanagi Hiroshi , Ohmagari Norio , Doi Yohei , Sakaguchi Hiroki , Sonoyama Takuhiro , Ichihashi Genki , Sanaki Takao , Baba Keiko , Tsuge Yuko , Uehara Takeki
Published: December 2022

Background

This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic.

Methods

Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events.

Results

A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5–64.9%; mean age: 35.3–37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: −0.41 log10 50% tissue-culture infectious dose/mL; P < .0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity.

Conclusions

Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile.

Clinical Trials Registration

Japan Registry of Clinical Trials: jRCT2031210350 (https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350)
Chromosome-scaleAmaranthus tricolorgenome provides insights into the evolution of the genusAmaranthusand the mechanism of betalain biosynthesis
Authors: Wang Hengchao , Xu Dong , Wang Sen , Wang Anqi , Lei Lihong , Jiang Fan , Yang Boyuan , Yuan Lihua , Chen Rong , Zhang Yan , Fan Wei
Published: December 2022

Amaranthus tricolor is a vegetable and ornamental amaranth, with high lysine, dietary fibre and squalene content. The red cultivar of A. tricolor possesses a high concentration of betalains, which has been used as natural food colorants. Here, we constructed the genome of A. tricolor, the first reference genome for the subgenus Albersia, combining PacBio HiFi, Nanopore ultra-long and Hi–C data. The contig N50 size was 906 kb, and 99.58% of contig sequence was anchored to the 17 chromosomes, totalling 520 Mb. We annotated 27,813 protein-coding genes with an average 1.3 kb coding sequence and 5.3 exons. We inferred that A. tricolor underwent a whole-genome duplication (WGD) and that the WGD shared by amaranths occurred in the last common ancestor of subfamily Amaranthoideae. Moreover, we comprehensively identified candidate genes in betalain biosynthesis pathway. Among them, DODAα1 and CYP76ADα1, located in one topologically associated domain (TAD) of an active (A) compartment on chromosome 16, were more highly expressed in red leaves than in green leaves, and DODAα1 might be the rate-limiting enzyme gene in betalains biosynthesis. This study presents new genome resources and enriches our understanding of amaranth evolution, betalains production, facilitating molecular breeding improvements and the understanding of C4 plants evolution.
AI-AIF: artificial intelligence-based arterial input function for quantitative stress perfusion cardiac magnetic resonance
Authors: Scannell Cian M , Alskaf Ebraham , Sharrack Noor , Razavi Reza , Ourselin Sebastien , Young Alistair A , Plein Sven , Chiribiri Amedeo
Published: December 2022

Aims

One of the major challenges in the quantification of myocardial blood flow (MBF) from stress perfusion cardiac magnetic resonance (CMR) is the estimation of the arterial input function (AIF). This is due to the non-linear relationship between the concentration of gadolinium and the MR signal, which leads to signal saturation. In this work, we show that a deep learning model can be trained to predict the unsaturated AIF from standard images, using the reference dual-sequence acquisition AIFs (DS-AIFs) for training.

Methods and results

A 1D U-Net was trained, to take the saturated AIF from the standard images as input and predict the unsaturated AIF, using the data from 201 patients from centre 1 and a test set comprised of both an independent cohort of consecutive patients from centre 1 and an external cohort of patients from centre 2 (n = 44). Fully-automated MBF was compared between the DS-AIF and AI-AIF methods using the Mann–Whitney U test and Bland–Altman analysis. There was no statistical difference between the MBF quantified with the DS-AIF [2.77 mL/min/g (1.08)] and predicted with the AI-AIF (2.79 mL/min/g (1.08), P = 0.33. Bland–Altman analysis shows minimal bias between the DS-AIF and AI-AIF methods for quantitative MBF (bias of −0.11 mL/min/g). Additionally, the MBF diagnosis classification of the AI-AIF matched the DS-AIF in 669/704 (95%) of myocardial segments.

Conclusion

Quantification of stress perfusion CMR is feasible with a single-sequence acquisition and a single contrast injection using an AI-based correction of the AIF.
Illegal: The SolarWinds Hack under International Law
Authors: Coco Antonio , Dias Talita , van Benthem Tsvetelina
Published: December 2022

In late 2020, news surfaced about one of the most extensive attacks on an information technology (IT) supply chain to date. Hackers exploited a vulnerability in the update system of Orion, a network-monitoring and management software developed by the company SolarWinds. Malicious code embedded in Orion updates created a backdoor into the systems used by numerous private and public entities. This backdoor was then used to insert additional malware into affected systems – in particular, spyware to exfiltrate confidential or sensitive data. Considering both the importance of preserving the integrity of IT supply chains and the diverse risks of harm that attacks such as the SolarWinds hack give rise to, this article examines this cyber operation according to the relevant rules of international law – notably those on sovereignty, non-intervention, general due diligence duties and international human rights law. It concludes that the operation may have been illegal on multiple fronts.
Acute, periprocedural and longterm antithrombotic therapy in older adults
Authors: Andreotti Felicita , Geisler Tobias , Collet Jean-Philippe , Gigante Bruna , Gorog Diana A , Halvorsen Sigrun , Lip Gregory Y H , Morais Joao , Navarese Eliano Pio , Patrono Carlo , Rocca Bianca , Rubboli Andrea , Sibbing Dirk , Storey Robert F , Verheugt Freek W A , Vilahur Gemma
Published: December 2022

The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.
Acute ischaemic stroke: recent advances in reperfusion treatment
Authors: Widimsky Petr , Snyder Kenneth , Sulzenko Jakub , Hopkins Leo Nelson , Stetkarova Ivana
Published: December 2022

During the last 5–7 years, tremendous progress was achieved in the reperfusion treatment of acute ischaemic stroke during its first few hours from symptom onset. This review summarizes the latest evidence from randomized clinical trials and prospective registries with a focus on endovascular treatment using stent retrievers, aspiration catheters, thrombolytics, and (in selected patients) carotid stenting. Novel approaches in prehospital (mobile interventional stroke teams) and early hospital (direct transfer to angiography) management are described, and future perspectives (‘all-in-one’ laboratories with angiography and computed tomography integrated) are discussed. There is reasonable chance for patients with moderate-to-severe acute ischaemic stroke to survive without permanent sequelae when the large-vessel occlusion is removed by means of modern pharmaco-mechanic approach. Catheter thrombectomy is now the golden standard of acute stroke treatment. The role of cardiologists in stroke is expanding from diagnostic help (to reveal the cause of stroke) to acute therapy in those regions where such up-to-date Class I. A treatment is not yet available.
Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials
Authors: Costa Francesco , Montalto Claudio , Branca Mattia , Hong Sung-Jin , Watanabe Hirotoshi , Franzone Anna , Vranckx Pascal , Hahn Joo-Yong , Gwon Hyeon-Cheol , Feres Fausto , Jang Yangsoo , De Luca Giuseppe , Kedhi Elvin , Cao Davide , Steg Philippe Gabriel , Bhatt Deepak L , Stone Gregg W , Micari Antonio , Windecker Stephan , Kimura Takeshi , Hong Myeong-Ki , Mehran Roxana , Valgimigli Marco
Published: December 2022

Aims

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients.

Methods and results

A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61–0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64–0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65–0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation.

Conclusion

In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen.

Study registration

PROSPERO registration number CRD42021284004
Economic, ethical, and environmental sustainability of cardiac imaging
Authors: Picano Eugenio
Published: December 2022

Current cardiology guidelines assign a class of recommendation 1 for the diagnosis of chest pain to five imaging techniques based on either anatomic (coronary computed tomography angiography) or functional approaches, such as stress single-photon emission tomography, stress positron emission tomography, stress cardiovascular magnetic resonance, and stress echocardiography. The choice is left to the prescribing physician, based on local availability and expertise. However, the five techniques differ substantially in their cost, applicability based on patient characteristics, long-term risk, and environmental impact. The average European immediate cost ranges from 50 to 1000 euros. The radiation exposure ranges from 0 to 500 chest x-rays. The environmental footprint ranges from 3 to 300 kg of carbon dioxide emissions equivalent. The ethical code of the World Medical Association 2021 recommends the responsible use of healthcare money by doctors, with the minimization of potential damage to patients and the environment. The Euratom law 2013/directive 59 reinforces the justification principle and the optimization principle for medical radiation exposures, with the legal responsibility of both the referrer and the practitioner. A small cost, a minimal long-term risk, and a modest carbon emission per examination multiplied by billions of tests per year become an unaffordable economic burden in the short-term, significant population damage to public health over the years, and impacts on climate change in decades. The cardiology community may wish to adopt a more sustainable practice with affordable, radiation-optimized, and carbon-neutral practices for the benefit of patients, physicians, payers, and the planet.
The Development and Psychometric Evaluation of the Perceived Physical Literacy for Chinese Elderly Questionnaire
Authors: Wang Haocen , King Barbara , Yang Rumei
Published: December 2022

Background and Objectives

Physical literacy refers to a holistic view of physical activity (PA), which proposes that a person needs to be motivationally, physically, strategically, mentally, socially, and knowledgeably prepared to be and stay physically active. It has been recently introduced in the field of older adults’ PA. Our study sought to develop the Perceived Physical Literacy for Chinese Elderly Questionnaire (PPLCEQ) and evaluate its psychometric properties.

Research Design and Methods

We conducted qualitative interviews and literature reviews to develop the item pool. Expert panel review and cognitive interviewing were used to evaluate the questionnaire’s content validity. A convenience sample of 388 Chinese older adults was recruited to assess the questionnaire’s validity and reliability.

Results

The developed PPLCEQ includes 47 items. Consistent with the conceptual definition of physical literacy, exploratory factor analysis showed that the PPLCEQ is composed of 6 subscales. Participants’ PPLCEQ scores were moderately correlated to their leisure-time PA (r = 0.38, p < .001), PA maintenance (r = 0.44, ps < .001), and perceived competence for exercising regularly scores (r = 0.58, p < .001). Moreover, the Cronbach’s alpha and the test–retest reliability of the questionnaire were 0.88 and 0.70, respectively.

Discussion and Implications

Psychometric assessment results suggest that the PPLCEQ is a reliable and valid tool that can be used in future studies investigating Chinese older adults’ perceived physical literacy.
Comparing and integrating artificial intelligence and similarity search detection techniques: application to seismic sequences in Southern Italy
Authors: Scotto di Uccio Francesco , Scala Antonio , Festa Gaetano , Picozzi Matteo , Beroza Gregory C
Published: December 2022

Understanding mechanical processes occurring on faults requires detailed information on the microseismicity that can be enhanced today by advanced techniques for earthquake detection. This problem is challenging when the seismicity rate is low and most of the earthquakes occur at depth. In this study, we compare three detection techniques, the autocorrelation FAST, the machine learning EQTransformer, and the template matching EQCorrScan, to assess their ability to improve catalogues associated with seismic sequences in the normal fault system of Southern Apennines (Italy) using data from the Irpinia Near Fault Observatory (INFO). We found that the integration of the machine learning and template matching detectors, the former providing templates for the cross-correlation, largely outperforms techniques based on autocorrelation and machine learning alone, featuring an enrichment of the automatic and manual catalogues of factors 21 and 7, respectively. Since output catalogues can be polluted by many false positives, we applied refined event selection based on the cumulative distribution of their similarity level. We can thus clean up the detection lists and analyse final subsets dominated by real events. The magnitude of completeness decreases by more than one unit compared to the reference value for the network. We report b-values associated with sequences smaller than the average, likely corresponding to larger differential stresses than for the background seismicity of the area. For all the analysed sequences, we found that main events are anticipated by foreshocks, indicating a possible preparation process for main shocks at subkilometric scales.
Catastrophic health care expenditure and impoverishment in Bhutan
Authors: Sharma Jayendra , Pavlova Milena , Groot Wim
Published: December 2022

Monitoring financial hardship due to out-of-pocket spending on health care is a critical determinant of progress towards universal health coverage. This study investigates the occurrence, intensity and determinants of catastrophic health expenditure and impoverishment in Bhutan using three rounds of the cross-sectional Bhutan Living Standard Surveys carried out in 2007, 2012 and 2017. We use a composite financial hardship measure defined as households experiencing either catastrophic health expenditure or impoverished/further impoverished due to health spending or both. We calculated concentration indices to examine socio-economic inequalities. We used logistic regression to examine the factors associated with financial hardship. We find that, in the context of a significant increase in living standards, there is a sharp increase in the incidence of catastrophic health expenditure (using 40% of capacity to pay) and impoverishment (based on equivalized average food-share-based poverty line) between 2007 and 2017. In 2017, catastrophic health expenditure was estimated at 0.51%, impoverishment at 0.32% and further impoverishment at 1.93% of the population, cumulating to financial hardship affecting 2.55% of the population. Financial hardship particularly burdened rural dwellers and poorer households. Transportation costs almost doubled the risk of facing financial hardship. Households that were poor, had an unemployed head, were larger and had more elderly members had higher odds of financial hardship. This evidence should prompt policy and programmatic interventions to support Bhutan’s progress towards universal health coverage.
Exploring the impact of selection bias in observational studies of COVID-19: a simulation study
Authors: Millard Louise A C , Fernández-Sanlés Alba , Carter Alice R , Hughes Rachael A , Tilling Kate , Morris Tim P , Major-Smith Daniel , Griffith Gareth J , Clayton Gemma L , Kawabata Emily , Davey Smith George , Lawlor Deborah A , Borges Maria Carolina
Published: December 2022

Background

Non-random selection of analytic subsamples could introduce selection bias in observational studies. We explored the potential presence and impact of selection in studies of SARS-CoV-2 infection and COVID-19 prognosis.

Methods

We tested the association of a broad range of characteristics with selection into COVID-19 analytic subsamples in the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank (UKB). We then conducted empirical analyses and simulations to explore the potential presence, direction and magnitude of bias due to this selection (relative to our defined UK-based adult target populations) when estimating the association of body mass index (BMI) with SARS-CoV-2 infection and death-with-COVID-19.

Results

In both cohorts, a broad range of characteristics was related to selection, sometimes in opposite directions (e.g. more-educated people were more likely to have data on SARS-CoV-2 infection in ALSPAC, but less likely in UKB). Higher BMI was associated with higher odds of SARS-CoV-2 infection and death-with-COVID-19. We found non-negligible bias in many simulated scenarios.

Conclusions

Analyses using COVID-19 self-reported or national registry data may be biased due to selection. The magnitude and direction of this bias depend on the outcome definition, the true effect of the risk factor and the assumed selection mechanism; these are likely to differ between studies with different target populations. Bias due to sample selection is a key concern in COVID-19 research based on national registry data, especially as countries end free mass testing. The framework we have used can be applied by other researchers assessing the extent to which their results may be biased for their research question of interest.
Prevalence and Severity of Symptoms 3 Months After Infection With SARS-CoV-2 Compared to Test-Negative and Population Controls in the Netherlands
Authors: van der Maaden Tessa , Mutubuki Elizabeth N , de Bruijn Siméon , Leung Ka Yin , Knoop Hans , Slootweg Jaap , Tulen Anna D , Wong Albert , van Hoek Albert Jan , Franz Eelco , van den Wijngaard Cees C
Published: December 2022

Background

This prospective study assesses symptoms 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection compared to test-negative and population controls, and the effect of vaccination prior to infection.

Methods

Participants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2 test, or after invitation from the general population (population controls). After 3 months, participants indicated presence of 41 symptoms and severity of 4 symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection.

Results

In total, 9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At 3 months, 13 symptoms, and severity of fatigue, cognitive impairment, and dyspnea were significantly elevated incases compared to controls. Of cases, 48.5% reported ≥1 significantly elevated symptom compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could be determined for cases aged <65 years, and was significantly protective for loss of smell and taste but not for other symptoms.

Discussion

Three months after SARS-CoV-2 infection, almost half of cases report symptoms, which was higher than background prevalence and test-negative prevalence. Vaccination prior to infection was protective against loss of smell and taste in cases aged <65 years.
Quinolinyl β-enaminone derivatives exhibit leishmanicidal activity against Leishmania donovani by impairing the mitochondrial electron transport chain complex and inducing ROS-mediated programmed cell death
Authors: Rani Ankita , Khanikar Shilpika , Dutta Mukul , Katiyar Shivani , Qamar Tooba , Seth Anuradha , Agnihotri P K , Guha Rajdeep , Vishwakarma Jai N , Kar Susanta
Published: December 2022

Objectives

Previously, a series of side chain-modified quinolinyl β-enaminones was identified to possess significant activity against chloroquine-sensitive or -resistant Plasmodium falciparum and Brugia malayi microfilariae. The present study evaluates in vitro and in vivo activity of the series against Leishmania donovani and reports their mode of action.

Methods

The in vitro activity of 15 quinolinyl β-enaminone derivatives against Leishmania promastigotes and amastigotes was assessed by luciferase assay. The reduction of organ parasite burden was assessed by Giemsa staining in L. donovani-infected BALB/c mice and hamsters. Intracellular Ca2+ and ATP level in active derivative (3D)-treated promastigotes were determined by fluorescence and luminescence assays. Flow cytometry was performed to determine loss of mitochondrial membrane potential (MMP) using JC-1 dye, reactive oxygen species (ROS) generation using 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) dye, phosphatidylserine externalization by Annexin V-FITC staining and cell-cycle arrest by propidium iodide (PI) staining.

Results

Compounds 3A, 3B and 3D showed significant in vitro efficacy against L. donovani with IC50 < 6 µM and mild cytotoxicity (∼75% viability) at 25 µM on J774 macrophages. 3A and 3D at 50 mg/kg and 100 mg/kg reduced parasite burden (>84%) in infected mice and hamsters, respectively, whereas 3D-treated animals demonstrated maximum parasite burden reduction without organ toxicity. Mode-of-action analysis revealed that 3D induced apoptosis by inhibiting mitochondrial complex II, reducing MMP and ATP levels, increasing ROS and Ca2+ levels, ultimately triggering phosphatidylserine externalization and sub-G0/G1 cell-cycle arrest in promastigotes.

Conclusions

Compound 3D-mediated inhibition of L. donovani mitochondrial complex induces apoptosis, making it a promising therapeutic candidate for visceral leishmaniasis.
Effect of ceftazidime/avibactam plus fosfomycin combination on 30 day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study
Authors: Oliva A , Volpicelli L , Di Bari S , Curtolo A , Borrazzo C , Cogliati Dezza F , Cona A , Agrenzano S , Mularoni A , Trancassini M , Mengoni F , Stefani S , Raponi G , Venditti M
Published: December 2022

Introduction

The primary outcome of the study was to evaluate the effect on 30 day mortality of the combination ceftazidime/avibactam + fosfomycin in the treatment of bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp).

Materials and methods

From October 2018 to March 2021, a retrospective, two-centre study was performed on patients with KPC-Kp BSI hospitalized at Sapienza University (Rome) and ISMETT-IRCCS (Palermo) and treated with ceftazidime/avibactam-containing regimens. A matched cohort (1:1) analysis was performed. Cases were patients receiving ceftazidime/avibactam + fosfomycin and controls were patients receiving ceftazidime/avibactam alone or in combination with in vitro non-active drugs different from fosfomycin (ceftazidime/avibactam ± other). Patients were matched for age, Charlson comorbidity index, ward of isolation (ICU or non-ICU), source of infection and severity of BSI, expressed as INCREMENT carbapenemase-producing Enterobacteriaceae (CPE) score.

Results

Overall, 221 patients were included in the study. Following the 1:1 match, 122 subjects were retrieved: 61 cases (ceftazidime/avibactam + fosfomycin) and 61 controls (ceftazidime/avibactam ± other). No difference in overall mortality emerged between cases and controls, whereas controls had more non-BSI KPC-Kp infections and a higher number of deaths attributable to secondary infections. Almost half of ceftazidime/avibactam + fosfomycin patients were prescribed fosfomycin without MIC fosfomycin availability. No difference in the outcome emerged after stratification for fosfomycin susceptibility availability and dosage. SARS-CoV-2 infection and ICS ≥ 8 independently predicted 30 day mortality, whereas an appropriate definitive therapy was protective.

Conclusions

Our data show that fosfomycin was used in the treatment of KPC-Kp BSI independently from having its susceptibility testing available. Although no difference was found in 30 day overall mortality, ceftazidime/avibactam + fosfomycin was associated with a lower rate of subsequent KPC-Kp infections and secondary infections than other ceftazidime/avibactam-based regimens.
Etizolam and Its Major Metabolites: A Short Review
Authors: Al Bahri Abdul Aziz , Hamnett Hilary J
Published: December 2022

Etizolam is a benzodiazepine (BZD). Etizolam is structurally different from BZDs as a thiophene replaces the benzene ring and a triazole ring is fused to the diazepine ring, but etizolam’s pharmacological profile is similar. Etizolam has been used to treat anxiety and panic disorders, to reduce depressive and somatization symptoms and to induce muscle relaxation. Etizolam is used recreationally due to its reinforcing and sedative effects. Etizolam is available in tablet or powder form or administered on blotter paper that can be placed on the tongue for oral absorption. Etizolam metabolizes into two major metabolites: α-hydroxyetizolam and 8-hydroxyetizolam, and all three compounds can be detected in different biological specimens using various common analytical techniques such as immunoassay, chromatography and mass spectrometry. Etizolam is a controlled drug in many countries around the globe but is approved for medical use in some countries, such as Japan, South Korea and Italy. This work is a collation and review of available literature on etizolam to help improve the fundamental understanding of its toxicology, outline best analytical practice, and aid interpretation of toxicology results.
Vibration data feature extraction and deep learning-based preprocessing method for highly accurate motor fault diagnosis
Authors: Jang Jun-Gyo , Noh Chun-Myoung , Kim Sung-Soo , Shin Sung-Chul , Lee Soon-Sup , Lee Jae-Chul
Published: December 2022

The environmental regulations on vessels being strengthened by the International Maritime Organization has led to a steady growth in the eco-friendly ship market. Related research is being actively conducted, including many studies on the maintenance and predictive maintenance of propulsion systems (including electric motors and rotating bodies) in electric propulsion vessels. The present study intends to enhance the artificial intelligence (AI)-based failure-diagnosis rate for electric propulsion vessel propulsion systems. To verify the proposed AI-based failure diagnosis algorithm for electric motors, this study utilized the vibration data of mechanical equipment (electric motors) in an urban railway station. Securing and preprocessing high-quality data is crucial for improving the failure-diagnosis rate, in addition to the performance of the diagnostic algorithm. However, the conventional wavelet transform method, which is generally used for machine signal processing, has a disadvantage of data loss when the data distribution is abnormal or skewed. This study, to overcome this shortcoming, proposes an AI-based denoising auto encoder (DAE) method that can remove noise while maintaining data characteristics for signal processing of mechanical equipment. This study preprocessed vibration data by using the DAE method, and extracted significant features from the data through the feature extraction method. The extracted features were utilized to train the one-class support vector machine model and to allow the model to diagnose the failure. Finally, the F-1 score was calculated by using the failure diagnosis results, and the most meaningful feature extraction method was determined for the vibration data. In addition, this study compared and evaluated the preprocessing performance based on the DAE and the wavelet transform methods.
Identification of MicroRNAs in the West Nile Virus Vector Culex tarsalis (Diptera: Culicidae)
Authors: Asad Sultan , Mehdi Ahmed M , Pujhari Sujit , Rückert Claudia , Ebel Gregory D , Rasgon Jason L
Published: December 2022

MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate gene expression during important biological processes including development and pathogen defense in most living organisms. Presently, no miRNAs have been identified in the mosquito Culex tarsalis (Diptera: Culicidae), one of the most important vectors of West Nile virus (WNV) in North America. We used small RNA sequencing data and in vitro and in vivo experiments to identify and validate a repertoire of miRNAs in Cx. tarsalis mosquitoes. Using bioinformatic approaches we analyzed small RNA sequences from the Cx. tarsalis CT embryonic cell line to discover orthologs for 86 miRNAs. Consistent with other mosquitoes such as Aedes albopictus and Culex quinquefasciatus, miR-184 was found to be the most abundant miRNA in Cx. tarsalis. We also identified 20 novel miRNAs from the recently sequenced Cx. tarsalis genome, for a total of 106 miRNAs identified in this study. The presence of selected miRNAs was biologically validated in both the CT cell line and in adult Cx. tarsalis mosquitoes using RT–qPCR and sequencing. These results will open new avenues of research into the role of miRNAs in Cx. tarsalis biology, including development, metabolism, immunity, and pathogen infection.
Physical Activity and Health-Related Quality of Life in Women With Breast Cancer: A Meta-Analysis
Authors: Aune Dagfinn , Markozannes Georgios , Abar Leila , Balducci Katia , Cariolou Margarita , Nanu Neesha , Vieira Rita , Anifowoshe Yusuf O , Greenwood Darren C , Clinton Steven K , Giovannucci Edward L , Gunter Marc J , Jackson Alan , Kampman Ellen , Lund Vivien , McTiernan Anne , Riboli Elio , Allen Kate , Brockton Nigel T , Croker Helen , Katsikioti Daphne , McGinley-Gieser Deirdre , Mitrou Panagiota , Wiseman Martin , Velikova Galina , Demark-Wahnefried Wendy , Norat Teresa , Tsilidis Konstantinos K , Chan Doris S M
Published: December 2022

Background

Physical activity (PA) is associated with improved health-related quality of life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund–American Institute for Cancer Research Continuous Update Project.

Methods

PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent expert panel graded the evidence.

Results

A total of 79 randomized controlled trials (14 554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy–Breast (WMD = 5.94, 95% confidence intervals [CI] = 2.64 to 9.24; I2 = 59%, n = 12), Functional Assessment of Cancer Therapy–General (WMD = 4.53, 95% CI = 1.94 to 7.13; I2 = 72%, n = 18), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–C30 (WMD = 6.78, 95% CI = 2.61 to 10.95; I2 = 76.3%, n = 17). The likelihood of causality was considered probable that PA improves HRQoL in breast cancer survivors. Effects were weaker for physical function and mental and emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions.

Conclusion

PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental and emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.
Preventing the Perfect Storm of Forest Mortality in the United States Caused by Invasive Species
Authors: Loehle Craig , Hulcr Jiri , Smith Jason A , Munro Holly L , Fox Tom
Published: December 2022

Invasive species are a growing global threat to forest ecosystems. In North America, previous invasions have functionally eliminated the American chestnut (Castanea dentata), a keystone and commercially important species in eastern North American forests, and currently threaten to eliminate other important species, such as ash (Fraxinus spp.), redbay (Persea borbonia), and eastern hemlock (Tsuga canadensis). Invasive species, particularly invasive insects, pathogens, and plants, threaten forest ecosystem integrity and put commercial forestry at risk. However, as the threat from invasive species grows due to expanding international trade, the scientific workforce with specialized expertise and training to mitigate current threats and, more importantly, avoid future threats, has been declining over the past 40 years. Research funding and administrative capacity to respond have also not kept pace with increased frequency and risk of species introductions. Herein, we review the nature of this ongoing challenge by examining contributing factors, including documenting trends in expertise and funding. In addition, we make recommendations for resources needed and information gaps that should be addressed and justify the need for increased support for basic biological research and further exploration of techniques to identify and treat potential threats (e.g., sentinel studies).

Study Implications: The US faces an invasive species crisis. Major tree species are already being decimated. The forest products industry relies primarily on a hand full of species. A new insect or disease could thus decimate the industry. We show that the pace of introductions has accelerated due to greater and faster shipping volume. Port screening and sanitation need considerable improvement, especially for live plants, which harbor insects and pathogens. Interior monitoring and overseas sentinal studies need enhancement for better detection of threats. More research and control staff are needed at government and university posts, especially to enable rapid response. Finally, research is needed on new detection and control technologies.
Strategies to Increase Workforce Diversity in Pediatric Infectious Diseases
Authors: Rogo Tanya , Holland Sabina , Fassiotto Magali , Maldonado Yvonne , Joseph Tuhina , Ramilo Octavio , Byrd Katrina , Delair Shirley
Published: December 2022

The number of physicians who are underrepresented in medicine within the pediatric infectious diseases workforce remains disproportionate compared to the US population. Physician workforce diversity plays an important role in reducing health care disparities. Pathways to careers in pediatric infectious diseases require that a diverse pool of students enter medicine and subsequently choose pediatric residency followed by subspecialty training. Efforts must be made to expose learners to pediatric infectious diseases earlier in the education timeline. Along with recruitment and creation of pathways, cultures of inclusivity must be created and fostered within institutions of learning along the entire spectrum of medical training.
Morgagni hernia: an uncommon pathology in adults
Authors: Rajkumar Karnan , Kulkarni Sayali , Talishinskiy Toghrul
Published: December 2022

Typically, diaphragmatic hernias occur as congenital defects and are considered a rare presentation when seen in adults. They occur as developmental defects and stem from embryonic components of the diaphragm not fusing completely. There are two types of diaphragmatic hernias, classified based on the location of herniation through the diaphragmatic defect. Bochdalek hernias present as defects in the left postero-lateral diaphragm, whereas Morgagni hernias present as anterior defects of the diaphragm. The more common defect of the two are Bochdalek hernias making Morgagni hernias a rare presentation. This case describes the presentation of a hernia through an anterior defect in the diaphragm, otherwise classified as a Morgagni hernia.
Soundness and completeness results for LEA and probability semantics
Authors: Moore Eoin
Published: December 2022

In Artemov (2020, J. Logic Comput., 30, 61–76), a logical system called the logic of evidence aggregation (LEA) was introduced, along with an intended semantics for it called probability semantics. The goal was to describe probabilistic evidence aggregation in the setting of formal logic. However, as noted in that paper, LEA is not complete with respect to probability semantics. This leaves the tasks open to find sound and complete semantics for LEA and a proper axiomatization for probability semantics. In this paper, we do both. We define a class of basic models called deductive basic models. We show LEA is sound and complete with respect to the class of deductive basic models. We also define an axiomatic system LEA$_+$ extending LEA and show it is sound and complete with respect to probability semantics. Along the way, we develop an intermediate system LEA$_-$ which, it turns out, is equivalent to propositional lax logic with a classical logic base. Sequent systems and decidability results for LEA$_-$ and LEA$_+$ are also presented.
Detecting planetary mass companions near the water frost-line using JWST interferometry
Authors: Ray Shrishmoy , Hinkley Sasha , Sallum Steph , Bonavita Mariangela , Squicciarini Vito , Carter Aarynn L , Lazzoni Cecilia
Published: December 2022

JWST promises to be the most versatile infrared observatory for the next two decades. The Near Infrared and Slitless Spectrograph (NIRISS) instrument, when used in the Aperture Masking Interferometry (AMI) mode, will provide an unparalleled combination of angular resolution and sensitivity compared to any existing observatory at mid-infrared wavelengths. Using simulated observations in conjunction with evolutionary models, we present the capability of this mode to image planetary mass companions around nearby stars at small orbital separations near the circumstellar water frost-line for members of the young, kinematic moving groups β Pictoris, TW Hydrae, as well as the Taurus–Auriga association. We show that for appropriately chosen stars, JWST/NIRISS operating in the AMI mode can image sub-Jupiter companions near the water frost-lines with ∼68 per cent confidence. Among these, M-type stars are the most promising. We also show that this JWST mode will improve the minimum inner working angle by as much as ∼50 per cent in most cases when compared to the survey results from the best ground-based exoplanet direct imaging facilities (e.g. VLT/SPHERE). We also discuss how the NIRISS/AMI mode will be especially powerful for the mid-infrared characterization of the numerous exoplanets expected to be revealed by Gaia. When combined with dynamical masses from Gaia, such measurements will provide a much more robust characterization of the initial entropies of these young planets, thereby placing powerful constraints on their early thermal histories.
An analysis of the effect of data processing methods on magnetic propeller models in short GRBs
Authors: Meredith Tomos R L , Wynn Graham A , Evans Philip A
Published: December 2022

We present analysis of observational data from the Swift Burst Analyser for a sample of 15 short gamma-ray bursts with extended emission (SGRBEEs) which have been processed such that error propagation from Swift’s count-rate-to-flux conversion factor is applied to the flux measurements. We apply this propagation to data presented by the Burst Analyser at 0.3–10 keV and also at 15–50 keV, and identify clear differences in the morphologies of the light curves in the different bands. In performing this analysis with data presented at both 0.3–10 keV, at 15–50 keV, and also at a combination of both bands, we highlight the impact of extrapolating data from their native bandpasses on the light curve. We then test these data by fitting to them a magnetar-powered model for SGRBEEs, and show that while the model is consistent with the data in both bands, the model’s derived physical parameters are generally very loosely constrained when this error propagation is included and are inconsistent across the two bands. In this way, we highlight the importance of the Swift data processing methodology to the details of physical model fits to SGRBEEs.