bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient markerless integration of genes in the chromosome of probiotic E. coli Nissle 1917 by bacterial conjugation
Authors: Seco Elena M. , Fernández Luis Ángel 
Published: November 2021

SummaryThe probiotic strain Escherichia coli Nissle 1917 (EcN) is a common bacterial chassis in synthetic biology developments for therapeutic applications given its long track record of safe administration in humans. Chromosomal integration of the genes of interest (GOIs) in the engineered bacterium offers significant advantages in genetic stability and to control gene dose, but common methodologies relying on the transformation of EcN are inefficient. In this work, we implement in EcN the use of bacterial conjugation in combination with markerless genome engineering to efficiently insert multiple GOIs at different loci of EcN chromosome, leaving no antibiotic resistance genes, vector sequences or scars in the modified bacterium. The resolution of cointegrants that leads to markerless insertion of the GOIs requires expression of I‐SceI endonuclease and its efficiency is enhanced by λ Red proteins. We show the potential of this strategy by integrating different genes encoding fluorescent and bioluminescent reporters (i.e. GFP, mKate2, luxCDABE) both individually and sequentially. We also demonstrate its application for gene deletions in EcN (ΔflhDC) and to replace the endogenous regulation of chromosomal locus (i.e. flhDC) by heterologous regulatory elements (e.g. tetR‐Ptet) in order to have an ectopic control of gene expression in EcN with an external inducer to alter bacterial behaviour (e.g. flagellar motility). Whole‐genome sequencing confirmed the introduction of the designed modifications without off‐target alterations in the genome. This straightforward approach accelerates the generation of multiple modifications in EcN chromosome for the generation of living bacterial therapeutics.
Residual lung damage following ARDS in COVID‐19 ICU survivors
Authors: Compagnone Nicola , Palumbo Diego , Cremona George , Vitali Giordano , De Lorenzo Rebecca , Calvi Maria Rosa , Del Prete Andrea , Baiardo Redaelli Martina , Calamarà Sabrina , Belletti Alessandro , Steidler Stephanie , Conte Caterina , Zangrillo Alberto , De Cobelli Francesco , Rovere‐Querini Patrizia ,   COVID‐BioB Study Group, Monti Giacomo 
Published: November 2021

AbstractBackgroundCoronavirus disease 2019 acute respiratory distress syndrome (COVID‐19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID‐19 ARDS sequelae. We assessed the mid‐term lung status of COVID‐19 survivors and investigated factors associated with pulmonary sequelae.MethodsAll adult COVID‐19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations.ResultsForty‐nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89–105) days, whilst PFT after 142 (133–160) days. The median age was 58 (52–65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6–16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71–7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DLCO) was reduced by 59%, with a median per cent of predicted DLCO of 72.1 (57.9–93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs.ConclusionsBoth the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID‐19.
‘It all comes back to community!’: A qualitative study of Aboriginal Elders promoting cultural well‐being
Authors: Cox Terrance , Hoang Ha , Mond Jonathon , Cross Merylin 
Published: November 2021

AbstractObjectiveTo examine Australian Aboriginal Elders’ (Elders) views on their contributions to and their potential to contribute to the well‐being of their community.DesignParticipatory action research methodology was employed. Data collection methods included yarning interviews and group circle discussions. Data were thematically analysed.SettingThe project was undertaken in collaboration with Elders from a discrete Aboriginal community in rural/remote Tasmania, an island state in southern Australia.ParticipantsTwelve Aboriginal community Elders.InterventionN/A.Main outcome measuresN/A.ResultsElders were promoting cultural well‐being through interconnected themes of mentoring, cultural healing and seeking balance between health services and the community's cultural foundation. Cultural values, identity, community cohesion and connections to country were further embedded in these themes.ConclusionThe study findings draw attention to the age‐old wisdom of Aboriginal Elders, who actively promote cultural well‐being as a main determinant of community health.
The geometric and temporal evolution of fault‐related folds constrain normal fault growth patterns, Barents Sea, offshore Norway
Authors: Alghuraybi Ahmed , Bell Rebecca E. , Jackson Christopher A.‐L. 
Published: November 2021

AbstractExtensional growth folds form ahead of the tips of propagating normal faults. These folds can accommodate a considerable amount of extensional strain and they may control rift geometry. Fold‐related surface deformation may also control the sedimentary evolution of syn‐rift depositional systems. Thus, by examining the stratigraphic record, we can constrain the four‐dimensional evolution of extensional growth folds, which in turn provides a record of fault growth and broader rift history. Here, we use high‐quality 3D seismic reflection and borehole data from the SW Barents Sea, offshore northern Norway to determine the geometric and temporal evolution of extensional growth folds associated with a large, long‐lived, basement‐rooted fault. We show that the fault grew via the linkage of four segments, and that fault growth was associated with the formation of fault‐parallel and fault‐perpendicular folds that accommodated a substantial portion (10%–40%) of the total extensional strain. Several periods of fault‐propagation folding occurred in response to the periodic burial of the fault, with individual folding events (ca. 25 and 32 Myr) lasting a considered part of the ca. 130 Myr rift period. Our study supports previous suggestions that continuous (i.e. folding) as well as discontinuous (i.e. faulting) deformation must be explicitly considered when assessing total strain in an extensional setting. We also show that changes in the architecture of growth strata record alternating periods of folding and faulting and that the margins of rift‐related depocentres may be characterised by basinward‐dipping monoclines as opposed to fault‐bound scarps. Our findings have broader implications for our understanding of the structural, physiographic and tectonostratigraphic evolution of rift basins.
Bioinformatics screening of ETV4 transcription factor oncogenes and identifying small‐molecular anticancer drugs
Authors: I.V Ambily Nath , Nair Achuthsankar S. 
Published: November 2021

AbstractThis bioinformatics study aimed to identify ETV4 transcription factor oncogenes and outline anticancer drugs for these genes. First, we collected known 61 ETV4 cancer targets that were framed as two classes of queries to screen against the multiomics resources in GeneMANIA. This method accessed and added functionally similar 20 genes to each set. These data were interpreted by hub genes, network clustering, gene ontology, and pathway analyses, and the results confirmed that all resultant genes were cancer promoters. The ETS‐binding motifs were identified from the promoter regions of these genes. Thus, 23 ETV4 targets were figured and those involved in oncogenesis were filtered as the following 16 putative nodes: MMP8, MMP14, KDR, BRIP1, CXCR1, GRB14, SHC2, SHC4, SH2B1, SH2B2, INPPL1, PTPN3, GNG12, SEMA4D, RHOA, and SPSB2. The transcriptional regulation of these oncogenes was coordinated by an extensive miRNA network that found to deregulate many cancer pathways. Using DgIb database, the high quality 6 oncogene‐drug combinations (MMP8‐CHEMBL1231240, MMP8‐Aminomethylamide, CXCR1‐Reparixin, SEMA4D‐Pepinemab, RHOA‐Clausine E, and SPSB2‐CHEMBL175296) were proposed. These findings may advance our understanding of novel neoplastic gene nexus of ETV4 and design treatment strategies for its modulation.
Indicatives, Subjunctives, and the Falsity of the Antecedent
Authors: Skovgaard‐Olsen Niels , Collins Peter 
Published: November 2021

AbstractIt is widely held that there are important differences between indicative conditionals (e.g., “If the authors are linguists, they have written a linguistics paper”) and subjunctive conditionals (e.g., “If the authors had been linguists, they would have written a linguistics paper”). A central difference is that indicatives and subjunctives convey different stances toward the truth of their antecedents. Indicatives (often) convey neutrality: for example, about whether the authors in question are linguists. Subjunctives (often) convey the falsity of the antecedent: for example, that the authors in question are not linguists. This paper tests prominent accounts of how these different stances are conveyed: whether by presupposition or conversational implicature. Experiment 1 tests the presupposition account by investigating whether the stances project—remain constant—when embedded under operators like negations, possibility modals, and interrogatives, a key characteristic of presuppositions. Experiment 2 tests the conversational‐implicature account by investigating whether the stances can be cancelled without producing a contradiction, a key characteristic of implicatures. The results provide evidence that both stances—neutrality about the antecedent in indicatives and the falsity of the antecedent in subjunctives—are conveyed by conversational implicatures.
Long‐term effects of spasticity treatment, including selective dorsal rhizotomy, for individuals with cerebral palsy
Authors: MacWilliams Bruce A , McMulkin Mark L , Duffy Elizabeth A , Munger Meghan E , Chen Brian Po‐Jung , Novacheck Tom F , Schwartz Michael H ,   Selective Dorsal Rhizotomy Outcomes Research Team
Published: November 2021

AimTo understand the long‐term effects of comprehensive spasticity treatment, including selective dorsal rhizotomy (SDR), on individuals with spastic cerebral palsy.MethodThis was a pre‐registered, multicenter, retrospectively matched cohort study. Children were matched on age range and spasticity at baseline. Children at one center underwent spasticity treatment including SDR (Yes‐SDR, n=35) and antispastic injections. Children at two other centers had no SDR (No‐SDR, n=40 total) and limited antispastic injections. All underwent subsequent orthopedic treatment. Participants returned for comprehensive long‐term assessment (age ≥21y, follow‐up ≥10y). Assessment included spasticity, contracture, bony alignment, strength, gait, walking energy, function, pain, stiffness, participation, and quality of life.ResultsSpasticity was effectively reduced at long‐term assessment in the Yes‐SDR group and was unchanged in the No‐SDR group. There were no meaningful differences between the groups in any measure except the Gait Deviation Index (Yes‐SDR + 11 vs No‐SDR + 5) and walking speed (Yes‐SDR unchanged, No‐SDR declined 25%). The Yes‐SDR group underwent more subsequent orthopedic surgery (11.9 vs 9.7 per individual) and antispastic injections to the lower limbs (14.4 vs <3, by design).InterpretationUntreated spasticity does not cause meaningful impairments in young adulthood at the level of pathophysiology, function, or quality of life.
Quantitative evaluation of fetal ventricular function by speckle tracking echocardiography
Authors: Luo Ling , Liu Hanmin , Zhou Shu , Zhao Fumin , Zhu Qi , Guo Nan , Chen Jiao 
Published: November 2021

AbstractMethodsThe study included 59 patients with normal fetal heart structure, blood flow, and heart rhythm (fetal abnormality‐negative group) and 50 patients with abnormal fetal heart structure, blood flow, and/or heart rhythm (fetal abnormality‐positive group). Automated Cardiac Motion Quantification (aCMQ) was performed in both groups to obtain left and right ventricular endocardial global longitudinal strain (GLSendo), mid‐myocardial global longitudinal strain (GLSmid), and epicardial global longitudinal strain (GLSepi). Parameters between the two groups were compared and correlation analyses performed. A deformation analysis was performed by two trained observers, and reproducibility was assessed.ResultsThe fetal left ventricular and right ventricular global longitudinal strain (LV‐GLS and RV‐GLS, respectively) decreased in a gradient from the endocardium to the epicardium. LV‐GLS and RV‐GLS of all myocardial layers were lower in the fetal abnormality‐positive than ‐negative group (all P < 0.05). Correlation analysis showed that neither LV‐GLS nor RV‐GLS was significantly correlated with gestational age in the fetal abnormality‐negative group (all P > 0.05), whereas left ventricular GLSendo, GLSmid, and GLSepi were negatively correlated with gestational age in the fetal abnormality‐positive group (r = −.39 to −.44, all P < 0.05). Repeatability testing showed that the inter‐observer and intra‐observer intra‐class correlation coefficients for LV‐GLS and RV‐GLS in each myocardial layer were >.75 (all P < 0.001).ConclusionsAs a new speckle tracking echocardiography tool, aCMQ has feasibility and repeatability in evaluating myocardial deformation of the fetal ventricle. This technique might provide helpful information on ventricular myocardial deformation in fetal hearts with abnormal structure or rhythm for clinical guidance in pregnancy.
Uncommon presentation of coronary sinus endocarditis
Authors: Marschall Alexander , Delgado Calva Freddy , Martí Sánchez David , Rodriguez Torres Diego 
Published: November 2021

AbstractA 79‐year‐old man, who underwent femoropopliteal bypass surgery 1 month prior to admission, presented with fever and fatigue. ECG showed complete atrioventricular block. Transthoracic echocardiography was performed, revealing a round homogeneous right atrial mass and severe mitral regurgitation. Transoesophageal echocardiography revealed involvement the coronary sinus (CS). Computed tomography imaging demonstrated abscess of the atrioventricular sulcus and infiltration of the CS.
Antithrombotic therapy and clinical outcomes at 1 year in the Spanish cohort of the EORP‐AF Long‐term General Registry
Authors: Pérez Cabeza Alejandro I. , Rivera‐Caravaca José Miguel , Roldán‐Rabadán Inmaculada , García Seara Javier , Bertomeu‐Gonzalez Vicente , Leal Mariano , García‐Fernandez Amaya , Tercedor Sanchez Luis , Ayarra Maite , Ciudad Marianela , Castaño Sara , Maestre Ana , Anguita Manuel , Garcia Bolao Ignacio , Marín Francisco 
Published: November 2021

AbstractBackgroundAtrial fibrillation (AF) increases the risk of thromboembolism. We investigate the efficacy and safety of oral anticoagulation (OAC) therapy and explored the number needed to treat for net effect (NNTnet) of OAC in the Spanish cohort of the EURObservational Research Programme‐AF (EORP‐AF) Long‐term General Registry.MethodsThe EORP‐AF General Registry is a prospective, multicentre registry conducted in ESC countries, including consecutive AF patients. For the present analysis, we used the Spanish cohort, and the primary outcome was any thromboembolism (TE)/acute coronary syndrome (ACS)/cardiovascular death during the first year of follow‐up.Results729 AF patients were included (57.1% male, median age 75 [IQR 67–81] years, median CHA2DS2‐VASc and HAS‐BLED of 3 [IQR 2–5] and 2 [IQR 1–2], respectively). 548 (75.2%) patients received OAC alone (318 [43.6%] on VKAs and 230 [31.6%] on DOACs). After 1 year, the use of OAC alone showed lower rates of any TE/ACS/cardiovascular death (3.0%/year; p < 0.001) compared to other regimens, and non‐use of OAC alone (HR 4.18, 95% CI 2.12–8.27) was independently associated with any TE/ACS/cardiovascular death. Balancing the effects of treatment, the NNTnet to provide an overall benefit of OAC therapy was 24. The proportion of patients on OAC increased at 1 year (87% to 88.1%), particularly on DOACs (33.6% to 39.9%) (p = 0.015), with low discontinuation rates.ConclusionsIn this contemporary cohort of AF patients, OAC therapy was associated with better clinical outcomes at 1 year and positive NNTnet. OAC use slightly increased during the follow‐up, with low discontinuation rates and higher prescription of DOACs.
Effects of fastigial nucleus electrostimulation on cardiac nerve regeneration, neurotransmitter release, and malignant arrhythmia inducibility in a post‐infarction rat model
Authors: Su Mouxiao , Luo Zhi , Yu Jiang , Zhang Runfeng , Wang Jisheng , Huang Changquan , Li Wensong , Yuan Wei , Zhang Heng , Cai Guocai , Shen Songlin 
Published: November 2021

AbstractThe reduced density of cardiac autonomic nerves plays an important role in malignant arrhythmia after myocardial infarction (MI). Previous studies have shown that there is an interaction between the brain and the heart, and fastigial nucleus electrostimulation (FNS) promotes central nerve regeneration. Whether and how it can promote cardiac nerve regeneration after MI and the underlying mechanisms remain unknown. This study investigated whether FNS promotes cardiac nerve regeneration and reduces malignant arrhythmia inducibility in a post‐infarction rat model. Ninety‐eight Wistar rats were randomly assigned to Sham control, MI (left anterior descending coronary artery ligation without FNS), FNS (MI plus FNS), and FNL (fastigial nucleus lesion plus FNS plus MI) groups. The frequency of malignant arrhythmia was significantly lower in the FNS group than in the MI and FNL groups. The density of cardiac autonomic nerves was less in the MI group than in the Sham group, which was promoted by FNS. The nerve growth factor (NGF) mRNA expression was downregulated in the MI group compared to the Sham group, which was significantly enhanced by FNS. The expression levels of norepinephrine (NE) and acetylcholine (ACh) were higher and lower respectively in the MI and FNL groups than in the Sham group. After FNS, NE concentration was reduced and Ach level was elevated compared to the MI group. These data suggested that FNS promoted the regeneration of cardiac autonomic nerves and reduced the incidence of malignant arrhythmias in MI rat model. The mechanisms might involve up‐regulation of NGF mRNA expression, decrease of NE release and increase of ACh release.
Fatigue response of additively manufactured Maraging Stainless Steel CX and effects of heat treatment and surface finishing
Authors: Ćirić‐Kostić Snežana , Croccolo Dario , De Agostinis Massimiliano , Fini Stefano , Olmi Giorgio , Paiardini Luca , Robusto Francesco , Šoškić Zlatan , Bogojević Nebojša 
Published: November 2021

AbstractThis paper deals with the novel topic of the fatigue response of additively manufactured Maraging Stainless Steel CX. A two‐by‐two factorial plan was arranged, to experimentally assess the effects of heat treatment and machining on the fatigue strength in both finite and infinite life domains. The two factors were regarded as on–off, taking the untreated unmachined condition as a reference for comparisons. Cylindrical specimens with vertical build orientation were involved in the fatigue campaign under four‐point rotating bending. The results indicate that the fatigue strength may be remarkably incremented (up to five times) with respect to the as received conditions, especially thanks to surface smoothing and taking advantage of a very low porosity level. Heat treatment strengthening mechanisms were also interpreted in the light of optical and electron microscope observations. Fatigue enhancement arises from precipitate size increment throughout the conducted heat treatment, although the fracture mode turns to be more brittle.
Who’s slipping through the cracks? A comprehensive individual, clinical and health system characterization of people with virological failure on first‐line HIV treatment in Uganda and South Africa
Authors: Reynolds Zahra , McCluskey Suzanne M. , Moosa Mahomed Yunus S. , Gilbert Rebecca F. , Pillay Selvan , Aturinda Isaac , Ard Kevin L. , Muyindike Winnie , Musinguzi Nicholas , Masette Godfrey , Moodley Pravi , Brijkumar Jaysingh , Rautenberg Tamlyn , George Gavin , Johnson Brent A. , Gandhi Rajesh T. , Sunpath Henry , Marconi Vincent C. , Bwana Mwebesa Bosco , Siedner Mark J. 
Published: November 2021

AbstractObjectivesHIV virological failure remains a major threat to programme success in sub‐Saharan Africa. While HIV drug resistance (HIVDR) and inadequate adherence are the main drivers of virological failure, the individual, clinical and health system characteristics that lead to poor outcomes are not well understood. The objective of this paper is to identify those characteristics among people failing first‐line antiretroviral therapy (ART).MethodsWe enrolled a cohort of adults in HIV care experiencing virological failure on first‐line ART at five sites and used standard statistical methods to characterize them with a focus on three domains: individual/demographic, clinical, and health system, and compared each by country of enrolment.ResultsOf 840 participants, 51% were women, the median duration on ART was 3.2 years [interquartile range (IQR) 1.1, 6.4 years] and the median CD4 cell count prior to failure was 281 cells/µL (IQR 121, 457 cells/µL). More than half of participants [53%; 95% confidence interval (CI) 49–56%] stated that they had > 90% adherence and 75% (95% CI 72–77%) took their ART on time all or most of the time. Conversely, the vast majority (90%; 95% CI 86–92%) with a completed genotypic drug resistance test had any HIV drug resistance. This population had high health system use, reporting a median of 3 (IQR 2.6) health care visits and a median of 1 (IQR 1.1) hospitalization in the preceding 6 months.ConclusionsPatients failing first‐line ART in sub‐Saharan Africa generally report high rates of adherence to ART, have extremely high rates of HIV drug resistance and utilize significant health care resources. Health systems interventions to promptly detect and manage treatment failure will be a prerequisite to establishing control of the HIV epidemic.