bluuebunny/crossref_metadata_2025 huggingface dataset:
Preprint Highlight: Hyphal compartmentalization and sporulation in Streptomyces require the conserved cell division protein SepX
Authors: Lasker Keren
Published: April 2022

Most bacteria undergo binary division. Streptomyces, filamentous soil bacteria with a multicellular life cycle, have two functionally distinct modes of cell division: vegetative cross-wall formation and sporulation septation. Although sporulation septation is an important survival strategy, the physiological significance of cross-wall formation remains largely unknown. Using genetics and quantitative imaging, the authors identified a previously uncharacterized protein, SepX, essential for cross-wall formation and for efficient sporulation septation. Deletion of sepX caused severe growth defects, demonstrating the necessity for vegetative division. These results provide a genetic basis for future research into the regulation of bacterial multicellular development, including how cross-walls form, how they relate to fitness, and how the two distinct cell types are coordinated.
ODEbase: a repository of ODE systems for systems biology
Authors: Lüders Christoph , Sturm Thomas , Radulescu Ovidiu
Published: April 2022

Recently, symbolic computation and computer algebra systems have been successfully applied in systems biology, especially in chemical reaction network theory. One advantage of symbolic computation is its potential for qualitative answers to biological questions. Qualitative methods analyze dynamical input systems as formal objects, in contrast to investigating only part of the state space, as is the case with numerical simulation. However, corresponding tools and libraries have a different set of requirements for their input data than their numerical counterparts. A common format used in mathematical modeling of biological processes is Systems Biology Markup Language (SBML). We illustrate that the use of SBML data in symbolic computation requires significant pre-processing, incorporating external biological and mathematical expertise. ODEbase provides suitable input data derived from established existing biomodels, covering in particular the BioModels database.

Availability and implementation

ODEbase is available free of charge at https://odebase.org.
Indications and utility of cardiac genetic testing in athletes
Authors: Castelletti Silvia , Gray Belinda , Basso Cristina , Behr Elijah R , Crotti Lia , Elliott Perry M , Gonzalez Corcia Cecilia M , D’Ascenzi Flavio , Ingles Jodie , Loeys Bart , Pantazis Antonis , Pieles Guido E , Saenen Johan , Sarquella Brugada Georgia , Sanz de la Garza Maria , Sharma Sanjay , Van Craenebroek Emeline M , Wilde Arthur , Papadakis Michael
Published: April 2022

Sports Cardiology practice commonly involves the evaluation of athletes for genetically determined cardiac conditions that may predispose to malignant arrhythmias, heart failure, and sudden cardiac death. High-level exercise can lead to electrical and structural cardiac remodelling which mimics inherited cardiac conditions (ICCs). Differentiation between ‘athlete’s heart’ and pathology can be challenging and often requires the whole armamentarium of available investigations. Genetic studies over the last 30 years have identified many of the genetic variants that underpin ICCs and technological advances have transformed genetic testing to a more readily available and affordable clinical tool which may aid diagnosis, management, and prognosis. The role of genetic testing in the evaluation and management of athletes with suspected cardiac conditions is often unclear beyond the context of specialist cardio-genetics centres. This document is aimed at physicians, nurses, and allied health professionals involved in the athlete’s care. With the expanding role and availability of genetic testing in mind, this document was created to address the needs of the broader sports cardiology community, most of whom work outside specialized cardio-genetics centres, when faced with the evaluation and management of athletes with suspected ICC. The first part of the document provides an overview of basic terminology and principles and offers guidance on the appropriate use of genetic testing in the assessment of such athletes. It outlines key considerations when contemplating genetic testing, highlighting the potential benefits and pitfalls, and offers a roadmap to genetic testing. The second part of the document presents common clinical scenarios in Sports Cardiology practice, outlining the diagnostic, prognostic, and therapeutic implications of genetic testing, including impact on exercise recommendations. The scope of this document does not extend to a comprehensive description of the genetic basis, investigation, or management of ICCs.
Description of Acinetobacter ihumii sp. nov., Microbacterium ihumii sp. nov., and Gulosibacter massiliensis sp. nov., three new bacteria isolated from human blood
Authors: Yacouba Abdourahamane , Sissoko Sibiri , Tchoupou Saha Ornella La Fortune , Haddad Gabriel , Dubourg Grégory , Gouriet Frédérique , Tidjani Alou Maryam , Alibar Stéphane , Million Matthieu , Lagier Jean-Christophe , Raoult Didier , Fenollar Florence , Fournier Pierre-Edouard , Lo Cheikh Ibrahima
Published: April 2022

Blood is precious tissue that is normally sterile. With the aim of diagnosing the cause of bacteremia, three bacterial strains were isolated from three different individuals. Strains Marseille-P7157T and Marseille-Q2854T are Gram-stain positive, non-spore-forming rod-shaped bacteria, while strain Marseille-P8049T is a Gram-stain negative, motile, non-spore-forming and rod-shaped bacterium. The major fatty acids found (>30%) were hexadecanoic acid for strain Marseille-P8049T and 12-methyl tetradecanoic acid for both strains Marseille-P7157T and Marseille-Q2854T. The 16S rRNA gene sequence analysis shows that strains Marseille-P8049 and Marseille-Q2854T have sequence similarity of 96.8%, 99.04%, and 98.3% with Acinetobacter ursingii strain LUH3792 (NR_025392.1), Gulosibacter faecalis strain B187 (NR_041812.1), and Schaalia canis strain CCUG 41706 (NR_025366.1), respectively. In addition, strains Marseille-Q2854T, Marseille-P8049T and Marseille-P7157T shared with their closely related species cited above the following DDH values: 19.5%, 24.4%, and 20.2%, respectively. Based on these phenotypic and genomic findings, we consider that strains Marseille-P8049T (= CSUR P8049 = CECT 30350), Marseille-P2854T ( = CSUR Q2854 = CECT 30120) and Marseille-P7157T ( = CSUR P7157 = CECT 30048) are new bacterial species, for which the names Acinetobacter ihumii sp. nov., Microbacterium ihumii sp. nov., and Gulosibacter massiliensis sp. nov., are proposed.
A first 3-D shear wave velocity model of the Ischia Island (Italy) by HVSR inversion
Authors: Manzo Roberto , Nardone Lucia , Gaudiosi Guido , Martino Claudio , Galluzzo Danilo , Bianco Francesca , Di Maio Rosa
Published: April 2022

Following the Mw 3.9 earthquake that occurred in the Ischia island (Naples, southern Italy) on 21 August 2017, the local monitoring seismic network was significantly improved in terms of both number of stations and instrumentation performance. Due to the huge amount of collected seismic ambient noise data, in this paper we present a first 3-D shear wave velocity model of the island retrieved from the inversion of horizontal-to-vertical spectral ratio curves by fixing the shear wave velocities (Vs) and modifying the thicknesses to get the corresponding 1-D Vs models. We are confident about the robustness of the attained models since the inversion process provided a good convergence towards the best-fitting solutions. Then, a first 3-D velocity model was obtained by contouring all the 1-D models obtained for the selected seismic stations to highlight possible lateral variations of the layer thicknesses and to reconstruct the morphology of the deeper interface characterized by a high-impedance contrast. A good correspondence between the 3-D Vs model and the geological features of the island was observed, especially in the northern sector where most of the stations are installed. In particular, the top of the high-impedance contrast interface appears deeper in the northern coastal areas and shallower in the central sector. This result agrees with the structural settings of the island likely due to the resurgence of Mount Epomeo.
Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients
Authors: Chen Chao , Guan Min-Xin
Published: April 2022

Sensorineural hearing loss often results from damaged or deficient inner ear hair cells. Mitochondrial 12S rRNA 1555A>G mutation has been associated with hearing loss in many families. The m.1555A>G mutation is a primary factor underlying the development of hearing loss and TRMU allele (c.28G>T, p.Ala10Sser) encoding tRNA thiouridylase interact with m.1555A>G mutation to cause hearing loss. However, the tissue specificity of mitochondrial dysfunction remains elusive and there is no highly effective therapy for mitochondrial deafness. We report here the generation of induced pluripotent stem cells (iPSCs) from lymphoblastoid cell lines derived from members of an Arab-Israeli family (asymptomatic individual carrying only m.1555A>G mutation, symptomatic individual bearing both m.1555A>G and c.28G>T mutations, and control subject). The c.28G>T mutation in iPSC lines from a hearing-impaired subject was corrected by CRISPR/Cas9. These iPSCs were differentiated into otic epithelial progenitor (OEP) cells and subsequent inner ear hair cell (HC)-like cells. The iPSCs bearing m.1555A>G mutation exhibited mildly deficient differentiation into OEP and resultant HC-like cells displayed mild defects in morphology and electrophysiological properties. Strikingly, those HC-like cells harboring m.1555A>G and TRMU c.28G>T mutations displayed greater defects in the development, morphology and functions than those in cells bearing only m.1555A>G mutation. Transcriptome analysis of patients-derived HC-like cells revealed altered expressions of genes vital for mechanotransduction of hair cells. Genetic correction of TRMU c.28G>T mutation yielded morphologic and functional recovery of patient derived HC-like cells. These findings provide new insights into pathophysiology of maternally inherited hearing loss and a step toward therapeutic interventions for this disease.
Motivic Action on Coherent Cohomology of Hilbert Modular Varieties
Authors: Horawa Aleksander
Published: April 2022

We propose an action of a certain motivic cohomology group on the coherent cohomology of Hilbert modular varieties, extending conjectures of Venkatesh, Prasanna, and Harris. The action is described in two ways: on cohomology modulo $p$ and over ${\mathbb {C}}$, and we conjecture that they both lift to an action on cohomology with integral coefficients. The conjecture is supported by theoretical evidence based on Stark’s conjecture on special values of Artin $L$-functions and by numerical evidence in base change cases.
The Dirichlet Problem for a Class of Hessian Quotient Equations on Riemannian Manifolds
Authors: Chen Xiaojuan , Tu Qiang , Xiang Ni
Published: April 2022

In this paper, we consider the Dirichlet problem for a class of Hessian quotient equations involving a gradient term on the right-hand sides on Riemannian manifolds. Under the assumption of an admissible subsolution, we solve the existence and the uniqueness for the Dirichlet problem on compact Riemannian manifold, based on the a priori estimates for the solutions to the Hessian quotient type equations. Compared with the classical results for Hessian type equations, our results do not depend on the convexity assumption for the right-hand side of the equation.
Parabolic Frequency on Ricci Flows
Authors: Baldauf Julius , Kim Dain
Published: April 2022

This paper defines a parabolic frequency for solutions of the heat equation on a Ricci flow and proves its monotonicity along the flow. Frequency monotonicity is known to have many useful consequences; here it is shown to provide a simple proof of backwards uniqueness. For solutions of more general parabolic equations on a Ricci flow, this paper provides bounds on the derivative of the frequency, which similarly imply backwards uniqueness.
Counterfactual Reasoning in Art Criticism
Authors: Sun Angela
Published: April 2022

When we evaluate artworks, we often point to what an artist could have done or what a work could have been in order to say something about the work as it actually is. Call this counterfactual reasoning in art criticism. On my account, counterfactual claims about artworks involve comparative aesthetic judgments between actual artworks and hypothetical variations of those works. The practice of imagining what an artwork could have been is critically useful because it can help us understand how artworks achieve specific aesthetic effects. I conclude by responding to an objection to my account on the basis that it violates the widely accepted acquaintance principle in aesthetics, on which aesthetic judgments must be based on firsthand perceptual encounters with their objects.
Survival benefit of remdesivir in hospitalized COVID-19 patients with high SARS-CoV-2 viral loads and low-grade systemic inflammation
Authors: Padilla Sergio , Polotskaya Kristina , Fernández Marta , Gonzalo-Jiménez Nieves , de la Rica Alba , García José Alberto , García-Abellán Javier , Mascarell Paula , Gutiérrez Félix , Masiá Mar
Published: April 2022

Objectives

To assess the benefits of remdesivir in hospitalized COVID-19 patients receiving combined immunomodulatory therapy (CIT) with dexamethasone and tocilizumab.

Methods

This was a cohort study of microbiologically confirmed COVID-19 hospitalized patients. The primary outcome was all-cause 28 day mortality. Secondary outcomes were need for invasive mechanical ventilation (IMV) and IMV/death. Subgroup analyses according to SARS-CoV-2 cycle threshold (Ct) values and inflammation biomarkers were performed. Multivariable marginal structural Cox proportional hazards regression models were used to analyse the association between remdesivir therapy and the risk of outcomes of interest.

Results

Of 1368 hospitalized patients treated with corticosteroids, 1014 (74%) also received tocilizumab, 866 (63%) remdesivir and 767 (56%) tocilizumab + remdesivir. The 28 day mortality was 9% in the overall cohort, with an adjusted HR (aHR) of 0.32 (95% CI = 0.17–0.59) for patients receiving CIT. In the latter group, the 28 day mortality was 6.5%, with an aHR of 1.11 (95% CI = 0.57–2.16) for remdesivir use and there were no differences in secondary outcomes. The risk of primary and secondary outcomes with remdesivir differed by Ct and C-reactive protein (CRP) levels in patients receiving CIT: for 28 day mortality, the aHR was 0.48 (95% CI = 0.21–1.11) for Ct <25, 0.12 (95% CI = 0.02–0.66) for Ct <25 and <5 day symptom duration and 0.13 (95% CI = 0.03–0.50) for CRP <38 mg/L; for IMV and IMV/death, the aHR was 0.32 (95% CI = 0.13–0.77) and 0.33 (95% CI = 0.17–0.63), respectively, in patients with Ct <25.

Conclusions

The benefits of remdesivir administered with dexamethasone and tocilizumab in hospitalized COVID-19 patients differ depending on Ct and CRP. Remdesivir decreases the risk of mortality and need for IMV in patients with high viral loads and low-grade systemic inflammation.
COVID-Beat: a low-cost breath monitoring approach for people in quarantine during the pandemic
Authors: Atif Muhammad , Muralidharan Shapna , Ko Heedong , Yoo Byounghyun
Published: April 2022

Due to COVID-19, people have to adapt to the new lifestyle until scientists develop a permanent solution for this pandemic. Monitoring the respiration rate is very important for a COVID-infected person because the Coronavirus infects the pulmonary system of the person. Two problems that arise while monitoring the breath rate are: sensors are contact based and expensive for mass deployment. A conventional wearable breath rate monitoring system burdens the COVID-affected patient and exposes the caregivers to possible transmission. A contactless low-cost breath monitoring system is required, which monitors and records the breath rate continuously. This paper proposes a breath rate monitoring system called COVID-Beat, a wireless, low-cost, and contactless Wi-Fi-based continuous breath monitoring system. This sensor is developed using off-the-shelf commonly available embedded Internet of Thing device ESP32, and the performance is validated by conducting extensive experimentation. The breath rate is estimated by extracting the channel state information of the subcarriers. The system estimates the breath rate with a maximum accuracy of 99% and a minimum accuracy of 91%, achieved by advanced subcarrier selection and fusion method. The experimental results show superior performance over the existing breath rate monitoring technologies.
Ethics-by-design: efficient, fair and inclusive resource allocation using machine learning
Authors: Papalexopoulos Theodore P , Bertsimas Dimitris , Cohen I Glenn , Goff Rebecca R , Stewart Darren E , Trichakis Nikolaos
Published: April 2022

The distribution of crucial medical goods and services in conditions of scarcity is among the most important, albeit contested, areas of public policy development. Policymakers must strike a balance between multiple efficiency and fairness objectives, while reconciling disparate value judgments from a diverse set of stakeholders. We present a general framework for combining ethical theory, data modeling, and stakeholder input in this process and illustrate through a case study on designing organ transplant allocation policies. We develop a novel analytical tool, based on machine learning and optimization, designed to facilitate efficient and wide-ranging exploration of policy outcomes across multiple objectives. Such a tool enables all stakeholders, regardless of their technical expertise, to more effectively engage in the policymaking process by developing evidence-based value judgments based on relevant tradeoffs.
Mitral regurgitation indirectly caused by giant left atrial myxoma: a case report
Authors: Nagatomi Shuji , Matsumoto Kazuhisa , Tateishi Naoki , Toyokawa Kenji , Mukaihara Kosuke , Soga Yoshiharu
Published: April 2022

Cardiac myxoma is a benign primary cardiac tumor. Herein, we report a case of mitral regurgitation due to annular dilatation caused by giant left atrial myxoma. The transthoracic echocardiogram performed in a 65-year-old man who suffered from worsening exertional dyspnea detected a large mass of 81 × 31 mm in the left atrium, causing functional severe mitral stenosis. Radical mass resection was performed. After removal of the aortic clamp, an intraoperative transesophageal echocardiogram revealed moderate mitral regurgitation due to annulus dilatation. Mitral annuloplasty was performed, and mitral regurgitation was controlled. The mass was diagnosed as myxoma histologically. A large myxoma that affects mitral annulus dilatation is rarely reported. Mitral regurgitation may be masked by the presence of a large myxoma. Therefore, it should be carefully evaluated after resection, and mitral annuloplasty should be considered in the presence of significant mitral regurgitation due to mechanical annulus dilatation caused by myxoma.
Tumour necrosis factor-α as a prognostic biomarker of severe malaria: a systematic review and meta-analysis
Authors: Mahittikorn Aongart , Mala Wanida , Srisuphanunt Mayuna , Masangkay Frederick Ramirez , Kotepui Kwuntida Uthaisar , Wilairatana Polrat , Kotepui Manas
Published: April 2022

Background

Tumour necrosis factor-alpha (TNF-α) levels are reportedly altered during malaria. In this systematic review and meta-analysis, we aimed to collect and compare data on TNF-α levels between patients with malaria of varying severity and healthy asymptomatic positive controls.

Methods

We searched PubMed, Scopus and Web of Science for studies that reported TNF-α levels in malaria cases of different severity and healthy asymptomatic positive controls using a combination of search terms. The quality of the included studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. To compare the TNF-α levels among fatal cases, severe cases, uncomplicated cases and healthy asymptomatic positive controls, we applied the random-effects model that assumed the existence of variations between studies. The effect estimate was pooled mean difference (MD) with a 95% confidence interval (CI).

Results

From 1694 studies, we included 31 studies that met our eligibility criteria for systematic review and meta-analysis. Patients with severe malaria showed higher mean TNF-α levels than those with uncomplicated malaria (P < 0.001, pooled MD = 79.02 pg/ml, 95% CI: 63.68–94.35 pg/ml, I2: 99.5%, n = 26 studies). Furthermore, fatal cases had no difference in the mean TNF-α levels in comparison with survived cases (P = 0.055, pooled MD = 82.38 pg/ml, 95% CI: −1.93 to 166.69 pg/ml, I2: 99.54%, n = 5 studies). Finally, patients with uncomplicated malaria showed higher mean TNF-α levels than those with asymptomatic malaria (P < 0.001, pooled MD = 45.10 pg/ml, 95% CI: 18.45–71.76 pg/ml, I2: 97.09%, n = 5 studies).

Conclusion

This systematic review and meta-analysis confirmed the increase of TNF-α levels in patients with severe malaria. Therefore, TNF-α may be alternatively used as a prognostic biomarker of severe malaria.

Trial registration

Not applicable.
The European Green Deal and nephrology: a call for action by the European Kidney Health Alliance
Authors: Vanholder Raymond , Agar John , Braks Marion , Gallego Daniel , Gerritsen Karin G F , Harber Mark , Noruisiene Edita , Pancirova Jitka , Piccoli Giorgina B , Stamatialis Dimitrios , Wieringa Fokko
Published: April 2022

The world faces a dramatic man-made ecologic disaster and healthcare is a crucial part of this problem. Compared with other therapeutic areas, nephrology care, and especially dialysis, creates an excessive burden via water consumption, greenhouse gas emission and waste production. In this advocacy article from the European Kidney Health Alliance we describe the mutual impact of climate change on kidney health and kidney care on ecology. We propose an array of measures as potential solutions related to the prevention of kidney disease, kidney transplantation and green dialysis. For dialysis, several proactive suggestions are made, especially by lowering water consumption, implementing energy-neutral policies, waste triage and recycling of materials. These include original proposals such as dialysate regeneration, dialysate flow reduction, water distillation systems for dialysate production, heat pumps for unit climatization, heat exchangers for dialysate warming, biodegradable and bio-based polymers, alternative power sources, repurposing of plastic waste (e.g. incorporation in concrete), registration systems of ecologic burden and platforms to exchange ecologic best practices. We also discuss how the European Green Deal offers real potential for supporting and galvanizing these urgent environmental changes. Finally, we formulate recommendations to professionals, manufacturers, providers and policymakers on how this correction can be achieved.
Small cell lung cancer recurring in the retina
Authors: Marks Sam , Woods Brian , Higgins Michaela , Connell Paul
Published: April 2022

Intraocular metastases are rare, usually isolating to the uveal tract. Retinal metastases are less common still, presenting a unique diagnostic and therapeutic challenge. This case observes a 66-year-old female ex-smoker presenting with unilateral painful vision loss 2 months from completion of definitive chemoradiotherapy for early-stage small cell lung cancer. A retinal lesion was discovered on examination and initially treated as viral retinitis without improvement. Two vitrectomy procedures were unable to confirm the diagnosis. Eventual retinal biopsy under general anaesthesia confirmed small cell lung cancer oligometastasis (7 months from completion of definitive chemoradiotherapy), without evidence of other sites of disease on imaging. She received local radiation to retina with resolution of eye pain. She eventually developed intrathoracic relapse of disease and was treated with palliative chemotherapy (14 months from completion of definitive chemoradiotherapy).
Vasospasm-induced ST-segment elevation myocardial infarction in a premenopausal woman with endothelial dysfunction
Authors: Takase Bonpei , Kobayashi Yukie , Sasaki Natsuko , Hayashi Katsumi , Hisada Tetsuya , Sakurada Masami , Masaki Nobuyuki , Nagata Masayoshi
Published: April 2022

ST-segment elevation myocardial infarction (STEMI) can be caused by coronary artery vasospasm (VSA) due to endothelial dysfunction. However, the clinical role of endothelial function tests in VSA-induced STEMI is not fully understood. We present the case of a 43-year-old woman with atypical chest pain and no coronary risk factors. STEMI caused by VSA was diagnosed. Flow-mediated vasodilatation (FMD) and EndPAT tests were performed; the FMD and reactive hyperaemia index were 3.8% and 1.23, respectively. Endothelial dysfunction is the putative cause of STEMI. FMD and EndPAT tests might be useful for predicting adverse outcomes in young premenopausal women with VSA.
Longitudinal changes in an autonomously functioning thyroid nodule with coexisting follicular thyroid carcinoma over 14 years
Authors: Uchida Taisuke , Yamaguchi Hideki , Kawabata Takayuki , Tanaka Hiroyuki , Kawano Fumiaki , Shimoda Kazuya
Published: April 2022

We present a female patient with autonomously functioning thyroid nodule (AFTN) and coexisting follicular thyroid carcinoma (FTC). At age 21, a left thyroid nodule was incidentally detected on computer tomography (CT) scan. At age 33, she had cervical compression and CT showed the left thyroid nodule had increased in size from 13 to 27 mm. Laboratory investigation showed subclinical hyperthyroidism with positive for anti-thyroid peroxidase antibody and normal level of serum thyroglobulin. Repeated fine needle aspiration cytology diagnosed with follicular neoplasm with Hashimoto’s thyroiditis. At age 35, she presented with palpitations due to overt hyperthyroidism. The left thyroid nodule increased in diameter to 33 mm, and thyroid scintigraphy showed elevated uptake in the left thyroid nodule, indicating an AFTN. Thyroidectomy was performed, and the left thyroid nodule was pathologically diagnosed with FTC with capsular invasion. In this case, the longitudinal increase in AFTN size suggested FTC and led to thyroidectomy.
Evidence for a Single Large Igneous Province at 2.11 Ga across Supercraton Superia
Authors: Davey Sarah C , Bleeker Wouter , Kamo Sandra L , Ernst Richard E , Cousens Brian L , Vuollo Jouni , Huhma Hannu
Published: April 2022

The Superia supercraton palaeogeographic reconstruction (c. 2.65–2.00 Ga) is predominantly based on the shared large igneous province (LIP) record of the Superior, Hearne, Wyoming, and Karelia-Kola Archaean cratons. Palaeogeographic reconstruction relies on U–Pb geochronology (i.e. magmatic barcodes), palaeolatitudes from palaeomagnetic studies, and geometry of mafic dyke swarms as part of LIPs, as well as similarities in cover stratigraphy and/or basement geology. If contemporaneous mafic units from these cratons are indeed fragments of the same LIP, then integration of their chemistry can provide insight into the overall LIP plumbing system.

A geochemical evaluation of whole-rock major and trace elements, and Nd isotopes, is presented for c. 2.11 Ga mafic units from the Marathon dykes (Superior), Griffin gabbro sills and Kazan dykes (Hearne), Bear Mountain dykes (Wyoming), and Tohmajärvi-Pirtguba dykes, Misi gabbro sills, and Oravaara and Hirsimaa volcanic rocks (Karelia-Kola). These units include the Nieminen dyke, Western Karelia, for which we present a new U–Pb CA-ID-TIMS date of 2114.4 ± 3.0 Ma.

Four geochemical groups are identified: Groups 1 (mid-ocean ridge basalt-like; in Karelia) and 2 (within plate basalt; in Hearne, Wyoming, and Karelia) are distinct end-members of upper mantle and plume melts, respectively; Group 3 (in Superior, Wyoming, and Karelia) is a hybrid of Groups 1 and 2; and Group 4 (in all cratons) formed by assimilation and fractional crystallisation of Groups 1, 2, and 3.

We present a model of the LIP plumbing system and define three magmatic stages by combining our geochemical interpretations with existing geochronology. The early stage (2135–2130 Ma) is limited to Group 1 dykes. The middle stage (2130–2113 Ma) includes Groups 1, 3, and 4. Onset of the late stage (2113–2101 Ma) is marked by the introduction of Group 2 but Groups 1 and 4 are also abundant. Finally, with our integrated tectonic and geochemical model, we discuss the mineralisation potential and prospectivity of the entire c. 2.11 Ga magmatic system.
Natural variation meets synthetic biology: Promiscuous trichome-expressed acyltransferases from Nicotiana
Authors: Schenck Craig A , Anthony Thilani M , Jacobs MacKenzie , Jones A Daniel , Last Robert L
Published: April 2022

Acylsugars are defensive, trichome-synthesized sugar esters produced in plants across the Solanaceae (nightshade) family. Although assembled from simple metabolites and synthesized by a relatively short core biosynthetic pathway, tremendous within- and across-species acylsugar structural variation is documented across the family. To advance our understanding of the diversity and the synthesis of acylsugars within the Nicotiana genus, trichome extracts were profiled across the genus coupled with transcriptomics-guided enzyme discovery and in vivo and in vitro analysis. Differences in the types of sugar cores, numbers of acylations, and acyl chain structures contributed to over 300 unique annotated acylsugars throughout Nicotiana. Placement of acyl chain length into a phylogenetic context revealed that an unsaturated acyl chain type was detected in a few closely related species. A comparative transcriptomics approach identified trichome-enriched Nicotiana acuminata acylsugar biosynthetic candidate enzymes. More than 25 acylsugar variants could be produced in a single enzyme assay with four N. acuminata acylsugar acyltransferases (NacASAT1–4) together with structurally diverse acyl-CoAs and sucrose. Liquid chromatography coupled with mass spectrometry screening of in vitro products revealed the ability of these enzymes to make acylsugars not present in Nicotiana plant extracts. In vitro acylsugar production also provided insights into acyltransferase acyl donor promiscuity and acyl acceptor specificity as well as regiospecificity of some ASATs. This study suggests that promiscuous Nicotiana acyltransferases can be used as synthetic biology tools to produce novel and potentially useful metabolites.
Injectable Biologics for Neuropathic Pain: A Systematic Review
Authors: Bies Michael , Ashmore Zachary , Qu Wenchun , Hunt Christine
Published: April 2022

Background

Neuropathic pain is a complex condition that can be refractory to conventional management and can cause persistent suffering in patients. Current pharmacologic treatments can provide temporary symptomatic relief; however, the mechanism of these therapies does not address the underlying cause of neuropathic pain. The use of injectable biologics for neuropathic pain has multiple proposed mechanisms for analgesia including attenuation of inflammatory mediated processes, arrest or delay of the degenerative process, inhibition of apoptotic pathways, and augmentation of the survival and recovery of injured and uninjured nerves.

Study Design

A systematic review of human studies involving the use of injectable biologics for neuropathic pain.

Methods

A comprehensive search of several data bases including Ovid MEDLINE ® and Epub Ahead of Print, In Process & Other Non-Indexed Citations and Daily, and Ovid Embase from inception to November 24, 2020.

Results

The initial search yielded 3,450 studies with an additional 6 studies identified through other resources. Twenty-seven studies were included after independent review by two of the investigators. The included studies assessed the efficacy of injectable biologics for the treatment of neuropathic pain defined as pain reduction. Secondary outcome measures included functional improvement as well as safety of the procedures. A qualitative assessment of the literature without meta-analysis was performed due to the heterogeneity of the data.

Conclusion

According to the GRADE criteria, there is very low certainty of evidence in support of the efficacy of injectable biologics for treatment of neuropathic pain. Future efforts should focus on creating a standardized methodology and study design with respect to preparation, dosage and route of administration of biologics. This will serve as a catalyst for higher quality randomized trials with generation of more useful data to help drive informed clinical decision making.
The Burden of National Debt: Evidence from Mergers and Acquisitions
Authors: Dissanayake Ruchith , Wu Yanhui , Zhang Huizhong
Published: April 2022

Increases in government debt are associated with a reduction in the yield spread between high-grade corporate bonds and long-term Treasuries and an increase in fiscal uncertainty. Consequently, increases in government debt significantly reduce the firm’s likelihood of acquisition. The effect is stronger among firms whose debt is a closer substitute for Treasuries and firms with greater exposure to fiscal uncertainty. A positive change in government debt motivates acquirers to avoid cash financing or more irreversible deals. The average deal quality is lower during periods of rising public debt, consistent with heightened fiscal uncertainty impeding monitoring and fostering “bad” deals. (JEL D80, E22, E62, G18, G34, G38).
Decolonizing Britain: An Exchange
Authors: Linstrum Erik , Ward Stuart , Ogle Vanessa , Nasar Saima , Gopal Priyamvada
Published: April 2022

Beginning in January 2021, Twentieth Century British History asked a group of scholars to reflect on what decolonization means to the field of British history. Twentieth Century British History co-editor Erik Linstrum (University of Virginia) posed questions over email for three rounds of discussion which concluded in December 2021. Stuart Ward (University of Copenhagen), Vanessa Ogle (University of California, Berkeley), and Saima Nasar (University of Bristol) took part. Priyamvada Gopal (Cambridge University) offered a final comment from the perspective of postcolonial studies. Contributions have been lightly edited but the relatively conversational style and flow of ideas in the original exchange have been preserved.
Examining unobserved factors associated with red light running in Vietnam: A latent class model analysis
Authors: Chu Tien Dung , Miwa Tomio , Bui Tuan Anh , Nguyen Quang Phuc , Vu Quang Huy
Published: April 2022

Red-light running (RLR) is a crucial violation that causes traffic accidents and injuries. Understanding factors that affect RLR is very significant to reduce the potential of this violation. Current studies have paid considerable attention to the observable factors, but not to unobservable factors. This study aims to examine the effects of observable and unobservable factors on RLR. This study uses a latent class model (LCM) to assign individuals into two classes—red-light-respectful and red-light-disrespectful road users—by surveying 751 respondents who use private transportation modes. This study incorporates psychological determinants into the LCM to account for unobservable factors. The contribution of this study is the in-depth investigation into law-respectful and law-disrespectful behaviours and intentional and unintentional violators. Such a study has not yet been conducted in the existing literature. In addition, a comprehensive comparison of the LCM and a traditional ordered probit model was conducted. Overall, the results suggest that the LCM is superior to the model that does not consider latent classes. Our estimation results are in alignment with previous studies on RLR: males, younger drivers/riders, less educated road users and motorcyclists are more likely to run red lights. An analysis of the latent variables shows that surrounding conditions—the behaviour of other violators, the absence of traffic police, and long waiting times—increase the possibility of violations. Based on these results, we provide suggestions to policymakers and traffic engineers: the implementation of enforcement cameras and penalties for violators are critical countermeasures to minimize the potential of RLR.
Psychological Problems Common in Children After PICU Admission
Authors: Rosenberg Karen
Published: April 2022

According to this study:

Children previously admitted to a pediatric intensive care unit have a high burden of psychological sequelae.

Risk stratification and early intervention are needed for high-risk groups.
Assessing Chest Pain
Authors: Cutugno Christine
Published: April 2022

Revised guidelines by a joint committee of the American College of Cardiology and the American Heart Association have been released to improve early identification and management of chest pain. Clinical goals of the guidelines are to identify life-threatening causes of chest pain, determine a patient's clinical stability, and assess whether the patient needs to be hospitalized or can safely be treated on an outpatient basis. For patients who don't require immediate intervention, risk stratification assessment and following clinical decision pathways are recommended.
Complement Activation in Patients With Heat-Related Illnesses: Soluble CD59 Is a Novel Biomarker Indicating Severity of Heat-Related Illnesses
Authors: Nakamura Yuki , Sueyoshi Koichiro , Miyoshi Yukari , Ishihara Tadashi , Hirano Yohei , Kondo Yutaka , Kuroda Yoko , Iwabuchi Kazuhisa , Okamoto Ken , Tanaka Hiroshi
Published: April 2022

OBJECTIVES:

Although multiple organ dysfunction syndrome (MODS) is the main cause of death in patients with heat-related illnesses, its underlying pathophysiological mechanism remains elusive. Complement activation is considered one of the main causes of MODS in patients with sepsis and trauma. Considering the pathophysiological similarity of heat related-illnesses with sepsis and trauma, the complement system might be activated in patients with heat-related illnesses as well. Our aim was to investigate whether excessive complement activation occurs in patients with heat-related illnesses.

DESIGN:

Prospective observational study.

SETTING:

Emergency department in the university hospital.

PATIENTS:

Thirty-two patients with heat-related illnesses and 15 age-matched healthy controls were enrolled in this study.

INTERVENTIONS:

Blood samples were collected from the study subjects for the measurement of complement factors.

MEASUREMENTS AND MAIN RESULTS:

Complement component 3a (C3a), complement component 5a (C5a), C5b-9, complement factor B (Ba), Factor H, and soluble CD59 in plasma were measured. The levels of C3a, C5a, C5b-9, and Ba significantly increased in patients with heat-related illnesses on day 0 compared with those in the healthy controls. Soluble CD59 was significantly high in patients with heat-related illnesses on day 0 and showed a correlation with the severity of the condition (Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and staging scores), Japanese Association for Acute Medicine disseminated intravascular coagulation scores, and the coagulation system (prothrombin time and fibrin degradation products).

CONCLUSIONS:

The complement system was activated in patients with heat-related illnesses, suggesting that it is one of the causes of MODS. Soluble CD59 may be a potent biomarker for the severity of heat-related illnesses.
Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer
Authors: Post Carl M. , Kahn Jenna M. , Turina Claire B. , Beer Tomasz M. , Hung Arthur Y.
Published: April 2022

Objectives:

In the era of dose-escalated prostate radiation therapy (RT), the use of androgen deprivation therapy (ADT) is undefined for intermediate-risk (IR) prostate cancer. There is growing concern of the risk of ADT to be detrimental to quality of life. This single-institution retrospective analysis aimed to evaluate outcomes of IR patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with or without concurrent/adjuvant short-term ADT.

Materials and Methods:

Data was collected from 260 consecutive patients treated with dose-escalated IMRT with daily image-guided RT for newly diagnosed IR prostate cancer. Biochemical recurrence-free survival (BCRFS), distant metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were calculated using Kaplan-Meier methodology.

Results:

Median follow-up was 93 months. A total of 181 patients had unfavorable IR disease, and 36.2% (N=94) received ADT, with median ADT duration of 6 months. Seven-year BCRFS was 94.1% vs. 86.2% (P=0.067), for ADT and no ADT, respectively, and no difference in distant metastasis-free survival or prostate cancer-specific survival was observed. ADT was associated with significantly worse 7-year OS (80.0% vs. 91.3%, P=0.010). Analysis of the unfavorable IR cohort alone, showed similar results; 7-year BCRFS and 7-year OS in patients who received ADT versus no ADT were 93.7% vs. 85.9% (P=0.093), and 79.0% vs. 90.6% (P=0.019), respectively.

Conclusions:

In our 15-year experience treating IR prostate cancer with dose-escalated IMRT with daily image-guided RT, short-term concurrent ADT was associated with a statistically significant worse OS. Additional studies are needed to determine if ADT is beneficial or detrimental for patients with IR prostate cancer treated with dose-escalated radiation.
Patients are Willing and Successful With Home Suture Removal After Mohs Surgical Procedures
Authors: Seger Edward W. , Neill Brett C. , Patel Soham , Siscos Spyros M. , Hocker Thomas L. H.
Published: April 2022

BACKGROUND

Suture removal after surgery is low risk; however, it is often performed by a medical provider. The current SARS-CoV-2 pandemic has forced providers to assess means of reducing in-person contact.

OBJECTIVE

To determine whether patients undergoing Mohs surgery are willing and successful with home suture removal.

MATERIALS AND METHODS

A prospective study was performed with patients undergoing Mohs surgery. Before their surgery, patients were assessed for their willingness to remove sutures before and after viewing educational material. Patients who were willing to attempt removal were contacted after expected suture removal date to verify success and assess their experience.

RESULTS

One hundred fifty patients were enrolled in the study. 90.1% were willing to attempt home suture removal. Patients were more willing (p = .003), more confident (p = .024), and had lower anxiety (p = .049) with removal after viewing educational resources. Patients with a history of suture removal were more likely to attempt removal after their procedure (p = .036). Ninety-seven percent of patients who were willing to attempt suture removal were successful. There were no major complications with removal.

CONCLUSION

Patients were overwhelmingly successful with suture removal after an educational intervention. Providers should consider providing this option after surgical procedures when clinically appropriate.
BARTONELLA HENSELAE–ASSOCIATED OPTIC NEUROPATHY PRESENTING AS A CENTRAL SCOTOMA IN THE ABSENCE OF OVERT PAPILLITIS: A MULTIMODAL IMAGING STUDY
Authors: Ng Caleb C. , McDonald H. Richard , Bern Bruce H. , Carson Michael D. , Cunningham Emmett T.
Published: April 2022

Background/Purpose:

The purpose of this report was to describe the use of multimodal imaging to establish the diagnosis of Bartonella henselae–associated optic neuropathy in a patient who presented with a central scotoma without overt evidence of optic nerve involvement.

Methods:

This was a case report. Main outcome measures included clinical, optical coherence tomography, and fluorescein angiography findings.

Observations:

A 72-year-old woman presented with a 3-day history of central scotoma in the left eye. Her examination was remarkable for faint exudation in the nasal macula of the left eye but was otherwise normal for her age. Spectral domain optical coherence tomography of the macula revealed mild thickening of the papillomacular bundle with scattered small cystoid spaces and several intraretinal exudates, none of which were visible clinically. Fluorescein angiography revealed localized leakage of the inferotemporal optic disc. When prompted, the patient recalled being scratched multiple times by her two pet kittens. Serial testing showed rising anti–B. henselae (B. henselae) immunoglobulin G antibody titers to 1:1,280, confirming the suspected diagnosis of B. henselae–associated optic neuropathy.

Conclusion:

Bartonella-associated optic nerve involvement can occur without overt evidence of optic disc swelling. Multimodal imaging can be used to suggest the diagnosis and support appropriate serologic testing.
Psychometric Evaluation of the Korean Version of the Functional Assessment of Chronic Illness Therapy-Fatigue
Authors: LEE Won-Gyeom , KIM Hee-Ju
Published: April 2022

Background

The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) instrument is a fatigue measure widely used on patients with cancer worldwide. The psychometric quality of the Korean version of the FACIT-Fatigue instrument has never been systematically evaluated.

Purpose

The purpose of this study was to assess the reliability and validity of the Korean version of the FACIT-Fatigue instrument.

Methods

This study used data collected from 170 patients with cancer and 120 healthy individuals. Internal consistency reliability was analyzed using Cronbach's α and item–total correlation. Construct validity was analyzed using confirmatory factor analysis, and known-group validity was tested using t tests. Convergent validity was analyzed using Pearson's correlation with pain and functional limitations. Predictive validity was analyzed using receiver operating characteristic curves.

Results

The Cronbach's α was .93 for the reliability evaluation, and the item–total correlation ranged from .27 to .84. In the construct validity evaluation, the bifactor model showed good fit (Q = 1.93, comparative fit index = .97, Tucker–Lewis index = .96, root mean square error of approximation = .05), indicating using the instrument's total score to be more appropriate than using the subscale scores (explained common variance = .76, ω = .95, ωH = .85, ωH/ω = .89). The group of patients with cancer showed significantly higher fatigue than the healthy subject group, showing known-group validity (t = −10.40, p < .05). Fatigue showed significant and strong correlations with functional limitations and pain (all ps < .001). The area under the curve was .81 (cutoff point = 40, Youden's index: 0.47, sensitivity: 77.60%, specificity: 73.04%), verifying that the instrument is predictive of higher fatigue severity in patients with cancer.

Conclusions/Implications for Practice

The Korean version of the FACIT-Fatigue instrument was shown to be reliable and valid. Its construct validity supports the use of the total scale score rather than the subscale scores.