bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered pharmacology and toxicology during ageing: implications for lung disease
Authors: Bast Aalt , Drent Marjolein
Published: June 2022

Purpose of review

Drug use in elderly people is high compared to younger people. Simultaneously, elderly are at greater risk when exposed to environmental substances. It is puzzling therefore, that ageing, as a variable in pharmacological and toxicological processes is not investigated in more depth. Moreover, recent data suggest that molecular manifestations of the ageing process also hallmark the pathogenesis of chronic lung diseases, which may impact pharmacology and toxicology.

Recent findings

In particular, absorption, distribution, metabolism and excretion (ADME) processes of drugs and toxins alter because of ageing. Polypharmacy, which is quite usual with increasing age, increases the risk of drug–drug interactions. Individual differences in combination of drugs use in conjunction with individual variations in drug metabolizing enzymes can influence lung function.

Exploring exposure throughout life (i.e. during ageing) to potential triggers, including polypharmacy, may avoid lung disease or unexplained cases of lung damage. Understanding of the ageing process further unravels critical features of chronic lung disease and helps to define new protective targets and therapies. Optimizing resilience can be key in pharmacology and toxicology and helps in maintaining healthy lungs for a longer period.
Role of biomarkers in lung nodule evaluation
Authors: Sethi Sonali , Cicenia Joseph
Published: June 2022

Purpose of review

Worldwide, lung cancer is the leading cause of cancer mortality. Much of this mortality is thought to be secondary to detection in later stages, where treatment options and survivability are limited. The goals of lung nodule evaluation are to expedite the diagnosis and treatment of patients with malignant nodules and to minimize unnecessary diagnostic procedures in those with benign nodules. However, the differentiation between benign and malignant has been challenging and is further complicated by the benefits of early diagnosis competing with potential morbidity of invasive diagnostic procedures.

Recent findings

Biomarkers have the potential to improve estimates of pretest probability of malignancy in pulmonary nodules, especially in the intermediate-risk subgroup. Four biomarkers have undergone extensive validation and are available for clinical use, and we will discuss each in this review.

The application of biomarkers to lung cancer risk assessment has the potential to improve cancer probability assessments, which in turn can reduce unnecessary invasive testing and/or reduce delays in diagnosis and treatment.
Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review
Authors: Moga Silvia , Teodorescu Andreea , Dragan Ana , Miron Ana Aliana , Ifteni Petru
Published: June 2022

Background:

Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19–positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19.

Areas of Uncertainty:

In clozapine-treated COVID-19–positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection?

Data Sources:

Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis.

Therapeutic Advances:

Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19–positive patients.

Results:

Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia.

Conclusions:

Clozapine treatment in COVID-19–positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2–infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results.
Challenges and opportunities in developing Actinium-225 radiopharmaceuticals
Authors: Dhiman Deeksha , Vatsa Rakhee , Sood Ashwani
Published: June 2022

Actinium-225 (225Ac) has emerged as a promising therapeutic radioisotope for targeted alpha therapy. It emits net four alpha particles during its decay to stable daughter bismuth-209, rightly called an in-vivo nano-generator. Compared to the worldwide demand of 225Ac, the amount produced via depleted thorium-229 sources is minimal, making it an expensive radionuclide. However, many research groups are working on optimizing the parameters for the production of 225Ac via different routes, including cyclotrons, reactors and high-energy linear accelerators. The present review article focuses on the various aspects associated with the development of 225Ac radiopharmaceuticals. It includes the challenges and opportunities associated with the production methods, labeling chemistry, in-vivo kinetics and dosimetry of 225Ac radiopharmaceuticals. A brief description is also given about the 225Ac radiopharmaceuticals at preclinical stages, clinical trials and used routinely.
Investigation of the ongoing pulmonary defects with perfusion-single photon emission computed tomography/computed tomography in patients under anticoagulant therapy for coronavirus disease 2019–induced pulmonary embolism
Authors: Caliskaner Ozturk Buket , Atahan Ersan , Kibar Ali , Sager Sait , Borekci Sermin , Gemicioglu Bilun
Published: June 2022

Objective

It was aimed to reveal the continuing perfusion defect rates in patients with a diagnosis of pulmonary embolism (PE) due to COVID-19 who have completed the third month of anticoagulant therapy but whose symptoms or laboratory elevations continue.

Methods

Patients with COVID-19 who were diagnosed with PE by Q-SPECT-CT between 1 September 2020 and 1 November 2021, who underwent control Q-SPECT/CT were included in the study. Demographic characteristics, laboratory findings, and first and second Q-SPECT/CT evaluation results of the patients were recorded.

Results

It was observed that the pulmonary defect continued in Q-SPECT/CT in the third month of anticoagulant treatment in 58.3% of the patients diagnosed with PE due to COVID-19, and new defects developed in 6.3%. The persistence rate of segment defects was higher than that of subsegment defects. It was observed that the defects persisted more frequently in patients with a history of hospitalization due to COVID-19.

Conclusion

Perfusion defects may still be present in patients diagnosed with PE due to COVID-19 in the presence of persistent dyspnea/chest pain/D-dimer elevation after 3 months of treatment. Perfusion defect persistence rates are higher in defects more proximal to the subsegment level and in people with severe COVID-19, and extended treatment should be considered in these patients.
Imaging in stone diagnosis and surgical planning
Authors: Serrell Emily C. , Best Sara L.
Published: June 2022

Purpose of Review

Radiological imaging techniques and applications are constantly advancing. This review will examine modern imaging techniques in the diagnosis of urolithiasis and applications for surgical planning.

Recent Findings

The diagnosis of urolithiasis may be done via plain film X-ray, ultrasound (US), or contrast tomography (CT) scan. US should be applied in the workup of flank pain in emergency rooms and may reduce unnecessary radiation exposure. Low dose and ultra-low-dose CT remain the diagnostic standard for most populations but remain underutilized. Single and dual-energy CT provide three-dimensional imaging that can predict stone-specific parameters that help clinicians predict stone passage likelihood, identify ideal management techniques, and possibly reduce complications. Machine learning has been increasingly applied to 3-D imaging to support clinicians in these prognostications and treatment selection.

The diagnosis and management of urolithiasis are increasingly personalized. Patient and stone characteristics will support clinicians in treatment decision, surgical planning, and counseling.
Peripartum Cardiomyopathy and Spouses' Experiences of Persistent Uncertainty
Authors: Hess Rosanna F. , Donnenwirth Jo Ann
Published: June 2022

Purpose:

The purpose of this study was to explore the experiences of spouses whose wives had peripartum cardiomyopathy (PPCM).

Design & Methods:

Participants were recruited for this phenomenological study through online sites Facebook and SavetheMommies. Fifteen men from four countries participated through semistructured phone interviews conducted between October 2019 and August 2020. Data were analyzed using a modified version of the constant comparison method.

Results:

The overarching theme of spouses' experiences wasLiving with the ‘what ifs’ of persistent uncertainty. Four main themes were:Feeling the shock, Facing the challenge, Figuring out a new normal,andFinding meaning. Spouses had to deal with the fear of their wives' heart failure relapse or death, changed marital and parental roles, and unclear expectations of the future.

Clinical Implications:

PPCM is a rare complication of pregnancy with uncertain implications for the future that can have a profound impact on the woman's spouse and family. Our findings should alert nurses and other health care professionals to the need for emotional, spiritual, and informational support of spouses or partners of women who have PPCM. Nurses should include spouses and partners in care and communication to make sure they are as informed as possible, have their questions and concerns addressed as needed, and receive adequate follow-up support.
Compatible With Confusion: Phrasing Pitfalls in Anatomic Pathology Reports
Authors: Findeis Sarah K. , Huber Aaron R. , Whitney-Miller Christa L.
Published: June 2022

Diagnostic uncertainty and the communication of this uncertainty is inherent in all specialties of medicine. The surgical pathology community uses a wide variety of phrases to express diagnostic uncertainty, even though there is literature that has shown use of uncertainty phrases leads to misunderstandings. We present a case that shows how uncertainty phrasing in a final diagnosis contributed to confusion surrounding patient care and resulted in sending the case for outside consultation. In addition, we review the literature surrounding uncertainty phrasing and discuss reporting of altered or amended reports.
A Novel Nonantibiotic Gut-directed Strategy to Prevent Surgical Site Infections
Authors: Hyoju Sanjiv K. , Keskey Robert , Castillo Gerardo , Machutta Kaylie , Zaborin Alexander , Zaborina Olga , Alverdy John C.
Published: June 2022

Objective:

To determine the efficacy of an orally delivered phosphate-rich polymer, Pi-PEG, to prevent surgical site infection (SSI) in a mouse model of spontaneous wound infection involving gut-derived pathogens.

Background:

Evidence suggests that pathogens originating from the gut microbiota can cause postoperative infection via a process by which they silently travel inside an immune cell and contaminate a remote operative site (Trojan Horse Hypothesis). Here, we hypothesize that Pi-PEG can prevent SSIs in a novel model of postoperative SSIs in mice.

Methods:

Mice were fed either a standard chow diet (high fiber/low fat, SD) or a western-type diet (low fiber/high fat, WD), and exposed to antibiotics (oral clindamycin/intraperitoneal cefoxitin). Groups of mice had Pi-PEG added to their drinking water and SSI incidence was determined. Gross clinical infections wound cultures and amplicon sequence variant analysis of the intestinal contents and wound were assessed to determine the incidence and source of the developing SSI.

Results:

In this model, consumption of a WD and exposure to antibiotics promoted the growth of SSI pathogens in the gut and their subsequent presence in the wound. Mice subjected to this model drinking water spiked with Pi-PEG were protected against SSIs via mechanisms involving modulation of the gut-wound microbiome.

Conclusions:

A nonantibiotic phosphate-rich polymer, Pi-PEG, added to the drinking water of mice prevents SSIs and may represent a more sustainable approach in lieu of the current trend of greater sterility and the use of more powerful and broader antibiotic coverage.
New-onset Obesity After Lung Transplantation: Incidence, Risk Factors, and Clinical Outcomes
Authors: Jomphe Valérie , Bélanger Noémie , Beauchamp-Parent Caroline , Poirier Charles , Nasir Basil S. , Ferraro Pasquale , Lands Larry C. , Mailhot Geneviève
Published: June 2022

Background.

Lung transplant (LTx) recipients who gain weight after transplantation may experience an upward shift in body mass index (BMI) that places them in the obese category. The incidence, risk factors, and impact on metabolic health and mortality of new-onset obesity have not been documented in the LTx setting.

Methods.

This single-center retrospective study included 564 LTx recipients. Individuals were stratified according to their BMI trajectories from pretransplant evaluation up to 10 y posttransplant. New-onset obesity was defined as a pretransplant BMI <30 kg/m2 and posttransplant BMI >30 kg/m2. The incidence, risk factors, and posttransplant diabetes mellitus, metabolic syndrome, and mortality of recipients with new-onset obesity were compared with those of nonobese (BMI <30 kg/m2, pre/post-LTx), consistently obese (BMI >30 kg/m2, pre/post-LTx), and obese recipients with weight loss (BMI >30 kg/m2 pre-LTx, BMI <30 kg/m2 post-LTx).

Results.

We found that 14% of recipients developed obesity after transplantation. Overweight individuals (odds ratio [OR]: 9.01; 95% confidence interval [CI] [4.86-16.69]; P < 0.001) and candidates with chronic obstructive pulmonary disease (OR: 6.93; 95% CI [2.30-20.85]; P = 0.001) and other diagnoses (OR: 4.28; 95% CI [1.22-14.98]; P = 0.023) were at greater risk. Multivariable regression analysis showed that new-onset obesity was associated with a greater risk of metabolic syndrome (hazard ratio: 1.70; 95% CI [1.17-2.46]; P = 0.005), but not of posttransplant diabetes mellitus, than nonobesity. Recipients with new-onset obesity had a survival comparable to that of consistently obese individuals.

Conclusions.

A greater understanding of the multifaceted nature of post-LTx obesity may lead to interventions that are better tailored to the characteristics of these individuals.
Genome plasticity driven by aneuploidy and loss of heterozygosity in Trypanosoma cruzi
Authors: Cruz-Saavedra Lissa , Schwabl Philipp , Vallejo Gustavo A. , Carranza Julio C. , Muñoz Marina , Patino Luz Helena , Paniz-Mondolfi Alberto , Llewellyn Martin S. , Ramírez Juan David
Published: June 2022

Trypanosoma cruzi the causative agent of Chagas disease shows a marked genetic diversity and divided into at least six Discrete Typing Units (DTUs). High intra genetic variability has been observed in the TcI DTU, the most widely distributed DTU, where patterns of genomic diversity can provide information on ecological and evolutionary processes driving parasite population structure and genome organization. Chromosomal aneuploidies and rearrangements across multigene families represent an evidence of T. cruzi genome plasticity. We explored genomic diversity among 18 Colombian T. cruzi I clones and 15 T. cruzi I South American strains. Our results confirm high genomic variability, heterozygosity and presence of a clade compatible with the TcIdom genotype, described for strains from humans in Colombia and Venezuela. TcI showed high structural plasticity across the geographical region studied. Differential events of whole and segmental aneuploidy (SA) along chromosomes even between clones from the same strain were found and corroborated by the depth and allelic frequency. We detected loss of heterozygosity (LOH) events in different chromosomes, however, the size and location of segments under LOH varied between clones. Genes adjacent to breakpoints were evaluated, and retrotransposon hot spot genes flanked the beginning of segmental aneuploidies. Our results suggest that T. cruzi genomes, like those of Leishmania, may have a highly unstable structure and there is now an urgent need to design experiments to explore any potential adaptive role for the plasticity observed.
Test Submission HighWire
Authors: K T Sethilkumar
Published: June 2022

Test
Genomic and transcriptomic analysis of sacred fig (Ficus religiosa)
Authors: Ashalatha K. L. , Arunkumar Kallare P , Gowda Malali
Published: June 2022

Background

Peepal/Bodhi tree (Ficus religiosaL.) is an important, long-lived keystone ecological species. Communities on the Indian subcontinent have extensively employed the plant in Ayurveda, traditional medicine, and spiritual practices. The Peepal tree is often thought to produce oxygen both during the day and at night by Indian folks. The goal of our research was to produce molecular resources using whole-genome and transcriptome sequencing techniques.

Results

The complete genome of the Peepal tree was sequenced using two next-generation sequencers Illumina HiSeq1000 and MGISEQ-2000. We assembled the draft genome of 406 Mb, using a hybrid assembly workflow. The genome annotation resulted in 35,093 protein-coding genes; 53% of its genome consists of repetitive sequences. To understand the physiological pathways in leaf tissues, we analyzed photosynthetically distinct conditions: bright sunny days and nights. The RNA-seq analysis supported the expression of 26,479 unigenes. The leaf transcriptomic analysis of the diurnal and nocturnal periods revealed the expression of the significant number of genes involved in the carbon-fixation pathway.

Conclusions

This study presents a draft hybrid genome assembly forF. religiosaand its functional annotated genes. The genomic and transcriptomic data-derived pathways have been analyzed for future studies on the Peepal tree.
An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients
Authors: Gonçalves Bronner P. , Hall Matthew , Jassat Waasila , Balan Valeria , Murthy Srinivas , Kartsonaki Christiana , Semple Malcolm G. , Rojek Amanda , Baruch Joaquín , Reyes Luis Felipe , Dasgupta Abhishek , Dunning Jake , Citarella Barbara Wanjiru , Pritchard Mark , Martín-Quiros Alejandro , Sili Uluhan , Baillie J. Kenneth , Aryal Diptesh , Arabi Yaseen , Rashan Aasiyah , Angheben Andrea , Caoili Janice , Carrier François Martin , Harrison Ewen M. , Gómez-Junyent Joan , Figueiredo-Mello Claudia , Douglas James Joshua , Nor Mohd Basri Mat , Chow Yock Ping , Wong Xin Ci , Bertagnolio Silvia , Thwin Soe Soe , Streinu-Cercel Anca , Salazar Leonardo , Rishu Asgar , Rangappa Rajavardhan , Ong David S.Y. , Hashmi Madiha , Carson Gail , Diaz Janet , Fowler Rob , Kraemer Moritz U.G. , Wils Evert-Jan , Horby Peter , Merson Laura , Olliaro Piero L. ,   ISARIC Clinical Characterisation Group
Published: June 2022

Background

Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings.

Methods

Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries.

Results

Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61 – 0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population.

Conclusions

Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome.
Machine learning approaches for classification of Plasmodium falciparum life cycle stages using single-cell transcriptomes
Authors: Shukla Swarnim , Choudhuri Soham , Iragavarapu Gayathri Priya , Ghosh Bhaswar
Published: June 2022

Malaria, spread by the femaleAnophelesmosquito, is a highly fatal disease widespread in many parts of the world, causing 0.4 million deaths globally. Vital gene expressions form the basis in the detection of malaria infection levels. Quantification of malaria parasite infected RBCs and classification of its life cycle stages are done at macroscopic level by experts, for making informed decisions. Off late multiple computational approaches have been proposed to circumvent the problem of dimensionality leading to accurate predicted results. In this work a dimensionality reduction technique based on Genetic Algorithm (GA) is applied onP. falciparumsingle-cell transcriptomics to arrive at an optimized subset of features from the larger dataset. Features are chosen based on their class variants considering increased efficiency and accuracy, to separately transform the selected elements into a lower dimension. For the classification of the life cycle of malaria parasite based on single cell transcriptome data, a three-pronged approach employing the multiclass Support Vector Machine (SVM), Logistic Regression (LR) and Random Forest (RF) techniques is used. Distribution of cells was visualised and mapped using the R-based Seurat package. Further, we constructed protein interaction networks of the genes identified by the feature selection method and elucidated the role of the proteins in progression of the parasite through it’s life cycle. Our approach presents a novel protocol to implement ML techniques on scRNA seq datasets and subsequently harnessing the extracted information for biomarker/drug target detection.
An accurate and rapid Real-time PCR approach for human Monkeypox virus diagnosis
Authors: Wawina-Bokalanga Tony , Sklenovska Nikola , Vanmechelen Bert , Bloemen Mandy , Vergote Valentijn , Laenen Lies , André Emmanuel , Van Ranst Marc , Muyembe-Tamfum Jean-Jacques , Maes Piet
Published: June 2022

Background

Human monkeypox (MPX) is an emerging zoonotic disease caused by monkeypox virus (MPXV), which is endemic to Western and Central Africa. Despite being identified in captive monkeys in 1958, and in humans from the Democratic Republic of Congo (DRC) in 1970, a MPXV diagnostic test is not routinely implemented in diagnostic laboratories. Currently, a multi-country outbreak of MPXV has been ongoing in several European and American countries since May 2022.

Methods

To develop this real-time PCR assay, five MPXV positive DNA samples were tested using MPXV-specific primers. The qPCR amplification was conducted on two different qPCR devices. We also tested samples, collected in May 2022, from pox-like lesions of MPXV-suspected patients in Belgium.

Results

The performance of our real-time PCR was proved with five MPXV positive DNA from DRC. In addition, five out of ten clinical samples, from the current MPXV-outbreak, tested positive with Ct values ranging from 20.6 to 34.9.

Conclusions

In this study, we present an accurate and rapid real-time PCR approach, based on conserved regions of both MPXV clades, that can be used to test clinical samples from MPXV-suspected persons. Our real-time qPCR assay can be used for the 2022 multi-country outbreak of human MPXV.

An accurate and fast real-time PCR assay is indispensable to diagnose cases of monkeypox during the 2022 multi-country outbreak.
OpenSAFELY: Representativeness of Electronic Health Record platform OpenSAFELY-TPP data compared to the population of England
Authors: Andrews Colm D , Schultze Anna , Curtis Helen J , Hulme William J , Tazare John , Evans Stephen JW , Mehrkhar Amir , Bacon Seb , Hickman George , Bates Chris , Parry John , Hester Frank , Harper Sam , Cockburn Jonathan , Evans David , Ward Tom , Davey Simon , Inglesby Peter , Goldacre Ben , MacKenna Brian , Tomlinson Laurie , Walker Alex J
Published: June 2022

Background

Since its inception in March 2020, data from the OpenSAFELY-TPP electronic health record platform has been used for more than 50 studies relating to the global COVID-19 emergency. OpenSAFELY-TPP data is derived from practices in England using SystmOne software, and has been used for the majority of these studies. We set out to investigate the representativeness of OpenSAFELY-TPP data by comparing it to national population estimates.

Methods

With the approval of NHS England, we describe the age, sex, Index of Multiple Deprivation and ethnicity of the OpenSAFELY-TPP population compared to national estimates from the Office for National Statistics. The five leading causes of death occurring between the 1st January 2020 and the 31st December 2020 were also compared to deaths registered in England during the same period.

Results

Despite regional variations, TPP is largely representative of the general population of England in terms of IMD (all within 1.1 percentage points), age, sex (within 0.1 percentage points), ethnicity and causes of death. The proportion of the five leading causes of death is broadly similar to those reported by ONS (all within 1 percentage point).

Conclusions

Data made available via OpenSAFELY-TPP is broadly representative of the English population.

Users of OpenSAFELY must consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. Although the coverage of TPP practices varies regionally across England, TPP registered patients are generally representative of the English population as a whole in terms of key demographic characteristics.

Key messages

There is regional variability across England in terms of key population characteristics

Users of OpenSAFELY should carefully consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research.

TPP registered patients are a representative sub-sample of the English population as a whole in terms of age, sex, IMD and ethnicity.

The proportions of the five leading causes of death in TPP in 2020 are broadly similar to those reported by ONS.
On the impacts of the COVID-19 pandemic on mortality: Lost years or lost days?
Authors: Rousson Valentin , Locatelli Isabella
Published: June 2022

Objective

To quantify the (direct and indirect) impacts of the COVID-19 pandemic on mortality for actual populations of persons living in 12 European countries in 2020.

Method

Based on demographic and mortality data, as well as remaining life expectancies found in the Human Mortality Database, we calculated a “population life lost” in 2020 for men and women living in Belgium, Croatia, Denmark, Finland, Hungary, Lithuania, Luxembourg, Norway, Portugal, Spain, Sweden and Switzerland. This quantity was obtained by dividing the total number of years lost in 2020 (estimated from all-cause mortality data and attributed directly or indirectly to COVID-19) by the size of the population.

Results

A significant population life loss was found in 8 countries in 2020, with men losing an average of 8.7, 5.0, 4.4, 4.0, 3.7, 3.4, 3.1 and 2.7 days in Lithuania, Spain, Belgium, Hungary, Croatia, Portugal, Switzerland and Sweden, respectively. For women, this loss was 5.5, 4.3, 3.7, 3.7, 3.1, 2.4, 1.6 and 1.4 days, respectively. No significant losses were found in Finland, Luxembourg, Denmark and Norway. Life loss was highly dependent on age, reaching 40 days at the age of 90 in some countries, while only a few significant losses occurred under the age of 60. Even in countries with a significant population life loss in 2020, it was on average about 30 times lower than in 1918, at the time of the Spanish flu.

Conclusions

Our results based on the concept of population life loss were consistent with those based on the classical concept of life expectancy, confirming the significant impact of COVID-19 on mortality in 8 European countries in 2020. However, while life expectancy losses were typically counted in months or years, population life losses could be counted in days, a potentially useful piece of information from a public health perspective.
Auto-detection of motion artifacts on CT pulmonary angiograms with a physician-trained AI algorithm
Authors: Dasegowda Giridhar , Bizzo Bernardo C , Kaviani Parisa , Karout Lina , Ebrahimian Shadi , Digumarthy Subba R , Neumark Nir , Hillis James , Kalra Mannudeep K , Dreyer Keith J
Published: June 2022

Purpose

Motion-impaired CT images can result in limited or suboptimal diagnostic interpretation (with missed or miscalled lesions) and patient recall. We trained and tested an artificial intelligence (AI) model for identifying substantial motion artifacts on CT pulmonary angiography (CTPA) that have a negative impact on diagnostic interpretation.

Methods

With IRB approval and HIPAA compliance, we queried our multicenter radiology report database (mPower, Nuance) for CTPA reports between July 2015 - March 2022 for the following terms: “motion artifacts,” “respiratory motion,” “technically inadequate,” and “suboptimal” or “limited exam.” All CTPA reports belonged to two quaternary (Site A, n= 335; B, n= 259) and a community (C, n= 199) healthcare sites. A thoracic radiologist reviewed CT images of all positive hits for motion artifacts (present or absent) and their severity (no diagnostic effect or major diagnostic impairment). Coronal multiplanar images belonging to 793 CTPA exams were de-identified and exported offline into an AI model building prototype (Cognex Vision Pro, Cognex Corporation) to train an AI model to perform two-class classification (“motion” or “no motion”) with data from the three sites (70% training dataset, n= 554; 30% validation dataset, n= 239). Separately, data from Site A and Site C were used for training and validating; testing was performed on the Site B CTPA exams. A 5-fold repeated cross-validation was performed to evaluate the model performance with accuracy and receiver operating characteristics analysis (ROC).

Results

Among the CTPA images from 793 patients (mean age 63 ± 17 years; 391 males, 402 females), 372 had no motion artifacts, and 421 had substantial motion artifacts. The statistics for the average performance of the AI model after 5-fold repeated cross-validation for the two-class classification included 94% sensitivity, 91% specificity, 93% accuracy, and 0.93 area under the ROC curve (AUC: 95% CI 0.89-0.97).

Conclusion

The AI model used in this study can successfully identify CTPA exams with diagnostic interpretation limiting motion artifacts in multicenter training and test datasets.

Clinical relevance

The AI model used in the study can help alert the technologists about the presence of substantial motion artifacts on CTPA where a repeat image acquisition can help salvage diagnostic information.
Ribosomal RNA operons define a central functional compartment in the Streptomyces chromosome
Authors: Lorenzi Jean-Noël , Thibessard Annabelle , Lioy Virginia S. , Boccard Frédéric , Leblond Pierre , Pernodet Jean-Luc , Bury-Moné Stéphanie
Published: June 2022

Streptomyces are prolific producers of specialized metabolites with applications in medicine and agriculture. These bacteria possess a large linear chromosome genetically compartmentalized: core genes are grouped in the central part, while terminal regions are populated by poorly conserved genes and define the chromosomal arms. In exponentially growing cells, chromosome conformation capture unveiled sharp boundaries formed by ribosomal RNA (rrn) operons that segment the chromosome into multiple domains. The first and last rrn operons delimit the highly expressed central compartment and the rather transcriptionally silent terminal compartments. Here we further explore the link between the genetic distribution of rrn operons and Streptomyces genomic compartmentalization. A large panel of genomes of species representative of the genus diversity revealed that rrn operons and core genes form a central skeleton, the former being identifiable from their core gene environment. We implemented a new nomenclature for Streptomyces genomes and trace their rrn-based evolutionary history. Remarkably, rrn operons are close to pericentric inversions. Moreover, the central compartment delimited by rrn operons has a very dense, nearly invariant core gene content. Finally, this compartment harbors genes with the highest expression levels, regardless of gene persistence and distance to the origin of replication. Our results highlight that rrn operons define the structural boundaries of a central functional compartment prone to transcription in Streptomyces.
Monitoring SARS-CoV-2 infection using a double reporter-expressing virus
Authors: Chiem Kevin , Park Jun-Gyu , Vasquez Desarey Morales , Plemper Richard K. , Torrelles Jordi B. , Kobie James J. , Walter Mark R. , Ye Chengjin , Martinez-Sobrido Luis
Published: June 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the highly contagious agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. An essential requirement for understanding SARS-CoV-2 fundamental biology and the impact of anti-viral therapeutics are robust methods to detect for the presence of the virus in infected cells or animal models. Despite the development and successful generation of recombinant (r)SARS-CoV-2 expressing fluorescent or luciferase reporter genes, knowledge acquired from their use in in vitro assays and/or in live animals are limited to the properties of the fluorescent or luciferase reporter genes. Herein, for the first time, we engineered a replication-competent rSARS-CoV-2 that expresses both fluorescent (mCherry) and luciferase (Nluc) reporter genes (rSARS-CoV-2/mCherry-Nluc) to overcome limitations associated with the use of a single reporter gene. In cultured cells, rSARS-CoV-2/mCherry-Nluc displayed similar viral fitness as rSARS-CoV-2 expressing single reporter fluorescent and luciferase genes (rSARS-CoV-2/mCherry and rSARS-CoV-2/Nluc, respectively), or wild-type (WT) rSARS-CoV-2, while maintaining comparable expression levels of both reporter genes. In vivo, rSARS-CoV-2/mCherry-Nluc has similar pathogenicity in K18 human angiotensin converting enzyme 2 (hACE2) transgenic mice than rSARS-CoV-2 expressing individual reporter genes, or WT rSARS-CoV-2. Importantly, rSARS-CoV-2/mCherry-Nluc facilitates the assessment of viral infection and transmission in golden Syrian hamsters using in vivo imaging systems (IVIS). Altogether, this study demonstrates the feasibility of using this novel bireporter-expressing rSARS-CoV-2 for the study SARS-CoV-2 in vitro and in vivo.

IMPORTANCE

Despite the availability of vaccines and antivirals, the coronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to ravage health care institutions worldwide. Previously, we have generated replication-competent recombinant (r)SARS-CoV-2 expressing fluorescent or luciferase reporter proteins to track viral infection in vitro and/or in vivo. However, these rSARS-CoV-2 are restricted to express only a single fluorescent or a luciferase reporter gene, limiting or preventing their use to specific in vitro assays and/or in vivo studies. To overcome this limitation, we have engineered a rSARS-CoV-2 expressing both fluorescent (mCherry) and luciferase (Nluc) genes and demonstrated its feasibility to study the biology of SARS-CoV-2 in vitro and/or in vivo, including the identification and characterization of neutralizing antibodies and/or antivirals. Using rodent models, we visualize SARS-CoV-2 infection and transmission through in vivo imaging systems (IVIS).
The Functional Landscape of SARS-CoV-2 3CL Protease
Authors: Iketani Sho , Hong Seo Jung , Sheng Jenny , Bahari Farideh , Culbertson Bruce , Atanaki Fereshteh Fallah , Aditham Arjun K. , Kratz Alexander F. , Luck Maria I. , Tian Ruxiao , Goff Stephen P. , Montazeri Hesam , Sabo Yosef , Ho David D. , Chavez Alejandro
Published: June 2022

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as the etiologic agent of COVID-19 (coronavirus disease 2019) has drastically altered life globally. Numerous efforts have been placed on the development of therapeutics to treat SARS-CoV-2 infection. One particular target is the 3CL protease (3CLpro), which holds promise as it is essential to the virus and highly conserved among coronaviruses, suggesting that it may be possible to find broad inhibitors that treat not just SARS-CoV-2 but other coronavirus infections as well. While the 3CL protease has been studied by many groups for SARS-CoV-2 and other coronaviruses, our understanding of its tolerance to mutations is limited, knowledge which is particularly important as 3CL protease inhibitors become utilized clinically. Here, we develop a yeast-based deep mutational scanning approach to systematically profile the activity of all possible single mutants of the SARS-CoV-2 3CLpro, and validate our results both in yeast and in authentic viruses. We reveal that the 3CLpro is highly malleable and is capable of tolerating mutations throughout the protein, including within the substrate binding pocket. Yet, we also identify specific residues that appear immutable for function of the protease, suggesting that these interactions may be novel targets for the design of future 3CLpro inhibitors. Finally, we utilize our screening results as a basis to identify E166V as a resistance-conferring mutation against the therapeutic 3CLpro inhibitor, nirmatrelvir, in clinical use. Collectively, the functional map presented herein may serve as a guide for further understanding of the biological properties of the 3CL protease and for drug development for current and future coronavirus pandemics.
Preparation of Yeast Cells for Staining
Authors: Rodig Scott J.
Published: June 2022

Staining yeast cells for the presence and location of antigens is particularly challenging. They are small, making the resolution of any antigen difficult; they have a thick cell wall that antibodies cannot penetrate and that is difficult to remove; and they grow in suspension, making handling difficult. In addition, background problems can be especially severe, particularly with polyclonal antibodies, because many antisera contain antibodies to yeast cell wall components. In this protocol, yeast cells are treated with paraformaldehyde, the cell wall is removed by enzymic digestion, and the spheroplasts are attached to poly-l-lysine-coated slides. After cell lysis, the cells are ready to be stained as per normal. Except in unusual circumstances, the detection reagent should be fluorochrome-labeled.
[1,4]Ditellurino[2,3-b:5,6-b′]dipyrazine
Authors: Franklin Donna , Lee Aundrea , Fronczek Frank R. , Junk Thomas
Published: June 2022

[1,4]Ditellurino[2,3-b:5,6-b′]dipyrazine represents the first reported [1,4]chalcogena[2,3-b:5,6-b′]dipyrazine containing a heavy chalcogens The asymmetric unit consists of three molecules. In contrast to its sulfur analog, which is planar [Lynch et al. (1994) Cryst. Struct. Commun.
50,1470–1472], C8H4N4Te2 is folded along the Te...Te axis to accommodate the larger chalcogenide atoms. The dihedral angle between the two Te2C2 rings of the central ring is 57.9° (mean of three). C—Te bond lengths range from 2.1105 (16) Å to 2.1381 (17) Å, in good agreement with those predicted by their covalent radii. All Te atoms are involved in intermolecular Te...N contacts, with distances in the range 2.894 (2) to 2.963 (2) Å. These result in a spiral supramolecular assembly, forming helical columns.
Linking entrepreneurial competencies, innovation and sustainable performance of manufacturing SMEs
Authors: Mokbel Al Koliby Ibraheem Saleh , Abdullah Haim Hilman , Mohd Suki Norazah
Published: June 2022

Purpose

The purpose of this study is twofold: to examine the impact of entrepreneurial competencies and innovation on manufacturing small and medium-sized enterprises' (SMEs) sustainable performance and to explore the role of innovation as a mediator on the relationship between entrepreneurial competencies and manufacturing SMEs' sustainable performance.

Design/methodology/approach

Data collected from manufacturing SMEs in Malaysia were analysed via the partial least squares-structural equation modelling (PLS-SEM) approach.

Findings

The results reveal that entrepreneurial competencies play a robust and noteworthy role in promoting innovation and the sustainable performance of manufacturing SMEs, respectively. Further, innovation has a partially mediated effect on the link between entrepreneurial competencies and manufacturing SMEs' sustainable performance. Manufacturing SMEs' aspirations to be the first to market with new products are reflected in these SMEs' implementation of positive entrepreneurial competencies or capabilities which enable them to scan the environment to identify high-quality business opportunities and respond through these SMEs' Research and Development (R&D) activities to create products that provide real benefit to customers' needs. Hence, these SME's seize the market opportunities.

Practical implications

Manufacturing SMEs' sustainable performance should be strengthened by linking entrepreneurial competencies with innovation to nurture greater agility to respond quickly to change and market demands. These SMEs should conduct tactical meetings on a regular basis to discuss current projects and assess critical indicators, as well as to identify and test fresh ideas for innovation and new business ventures in order to achieve sustainable performance in challenging business environments.

Originality/value

By applying the resource-based view (RBV) theory and the triple bottom line (TBL) framework into a single framework, this study highlights the role of innovation as a meaningful mediator between entrepreneurial competencies and manufacturing SMEs' sustainable performance. As exploration of this relationship has been very limited, the study makes a novel contribution to the extant literature.
Evaluation of risk factors in Ghanaian public-private-partnership (PPP) power projects using fuzzy synthetic evaluation methodology (FSEM)
Authors: Kukah Augustine Senanu Komla , Owusu-Manu De-Graft , Badu Edward , Edwards David John
Published: June 2022

Purpose

This paper aims to evaluate the risk factors and determines the overall risk level (ORL) of public-private-partnership (PPP) power projects in Ghana using fuzzy synthetic evaluation methodology (FSEM).

Design/methodology/approach

In this paper review of literature led to the development of a 67-factor risk list which was ranked by experts and industry practitioners through a questionnaire survey.

Findings

These factors were grouped into principal risk factors (PRFs) using component analysis and they served as the input variables for fuzzy analysis. The seven components were: Contract and Payment risks, Environmental risks, Financial and Cost risks, Legal and Guarantee risks, Operation risks, Socio-Political and Performance risks (SPR) and Tender and Negotiation risks. Study showed that the ORL of Ghanaian PPP power projects is high implying they are risky to both the public and private sectors. Fuzzy analysis also confirmed SPR as the most critical principal factor.

Originality/value

This study is significant and demonstrates that fuzzy methodology can be used as a useful risk evaluation tool and risk assessment framework for private investors, policy makers and public sector.
The cost-effectiveness of agricultural greenhouse gas reduction under diverse carbon policies in China
Authors: Tang Kai , Ma Chunbo
Published: June 2022

Purpose

Mitigating agricultural greenhouse gas (GHG) emissions is an essential part of China's effort to achieve net-zero emissions. This study assesses the cost-effectiveness of China's agricultural GHG reduction under diverse carbon policies.

Design/methodology/approach

The study employs a parametric non-radial distance function approach and estimates the technical abatement potential and marginal abatement cost (MAC) of GHG in China's agricultural sector for the 2008–2017 period.

Findings

Agriculture is expected to make a great contribution to China's net-zero emissions progress. This study empirically analyses the cost-effectiveness of China's agricultural GHG reduction under diverse carbon policies. A parametric non-radial distance function approach is used to derive technical abatement potential and MAC of GHG for the 2008–2017 period. The results indicate that no significant improvement had been achieved in terms of agricultural GHG reduction in China during 2008–2017. The country's agricultural sector could reduce 20–40% GHG emissions with a mean value of 31%. In general, western provinces have larger reduction potential than eastern ones. The average MAC for the whole country is 4,656 yuan/ton CO2e during 2008–2017. For most western provinces, their MAC values are considerably higher than those for most eastern provinces. Compared with previous sectoral estimates of GHG mitigation cost, this study’s estimates indicate that reducing agricultural GHG emissions in some provinces is likely to be cost-effective. The Chinese government should consider expanding its national carbon market to cover agricultural sector.

Practical implications

The Chinese government should consider expanding its national carbon market to cover agricultural sector.

Originality/value

Existing studies in the field mostly ignore input constraints, which is inconsistent with carbon mitigation policy practice, especially in the agricultural sector. This study’s approach integrates both input and output constraints reflecting differing policy practice.