bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Renin–Angiotensin–Aldosterone Inhibitors on Early Outcomes of Hypertensive COVID-19 Patients: A Randomized Triple-Blind Clinical Trial
Authors: Najmeddin Farhad , Solhjoo Maedeh , Ashraf Haleh , Salehi Mohammadreza , Rasooli Fatemeh , Ghoghaei Morteza , Soleimani Abbas , Bahreini Maryam
Published: July 2021

Background

The role of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has been addressed in some studies related to the current coronavirus disease-2019 (COVID-19) pandemic with possible higher severity and mortality in patients with hypertension. A triple-blind randomized controlled trial was designed to evaluate the effects of these medications on the COVID-19 progression.

Methods

Patients were enrolled in this trial between April and September 2020. They were randomized in 2 groups. The former dosage of ACEis/ARBs was continued in one group while in another group, the ACEis/ARBs were replaced by amlodipine ± carvedilol according to the dose equivalents. The primary outcomes were length of stay in hospitals and intensive care units (ICUs). Other outcomes include mechanical ventilation, noninvasive ventilation, readmission, and COVID-19 symptoms after discharge.

Results

We randomized 64 patients with COVID-19 into 2 groups. Most patients were aged 66–80 and 46–65 years-old, 33 (51.6%) and 27 (42.2%), respectively. The study groups were nearly similar in baseline vital signs and characteristics. In addition, there was no significant difference in terms of recorded systolic and diastolic blood pressure measurements between groups. Furthermore, we did not find a significant difference between the days of ICU or ward admission, the discharge rate, or readmission rates between the 2 groups.

Conclusions

This randomized triple-blind multicentric clinical trial did not show any deleterious effects of ACEi/ARB medications in hypertensive COVID-19 patients.

Clinical trials registration

The trial acquired the ethical code, IR.TUMS.VCR.REC.1399.028 and was registered in the Iranian randomized controlled trial system (registration no. IRCT20151113025025N3), https://en.irct.ir/trial/46531.
Urgent Need for a Comprehensive Public Health Response to Artisanal Small-Scale Mining
Authors: Gottesfeld Perry , Khoza Norman Nkuzi
Published: July 2021

Informal sector mining is a growing enterprise in countries around the world providing livelihood to >40 million self-employed miners. The use of mercury in gold processing has been the sole focus of most research and public health interventions in artisanal mining. Few programs work to improve health among communities mining other commodities including sand, aggregates, quartz, lead, gemstones, coal and other materials. Although mercury is a major environmental challenge in countries with extensive gold mining, artisanal miners are also exposed to silica dust, metals and other safety hazards. The available evidence regarding hazardous exposures among self-employed miners suggests that the public health implications are much broader. There is a growing body of evidence linking exposures to silica dust to tuberculosis and other lung diseases among artisanal miners. Studies have also documented exposures to lead and other metals including arsenic, cadmium, cobalt and chromium in informal mining communities. Silica-dust exposures are higher in artisanal mining than levels reported in large industrial mining. There is ample evidence that artisanal miners are experiencing health impacts not just from mercury but also from exposures to noise, silica dust and metals. Practical, low-cost solutions have been pilot tested and shown to reduce respirable silica dust and metal exposures among miners and ore processors. Governments, development agencies and global health funders should invest in comprehensive public health programs to respond to these needs.
Neonatal anesthesia and dysregulation of the epigenome
Authors: Cabrera Omar Hoseá , Useinovic Nemanja , Jevtovic-Todorovic Vesna
Published: July 2021

Each year, millions of infants and children are anesthetized for medical and surgical procedures. Yet, a substantial body of preclinical evidence suggests that anesthetics are neurotoxins that cause rapid and widespread apoptotic cell death in the brains of infant rodents and nonhuman primates. These animals have persistent impairments in cognition and behavior many weeks or months after anesthesia exposure, leading us to hypothesize that anesthetics do more than simply kill brain cells. Indeed, anesthetics cause chronic neuropathology in neurons that survive the insult, which then interferes with major aspects of brain development, synaptic plasticity, and neuronal function. Understanding the phenomenon of anesthesia-induced developmental neurotoxicity is of critical public health importance because clinical studies now report that anesthesia in human infancy is associated with cognitive and behavioral deficits. In our search for mechanistic explanations for why a young and pliable brain cannot fully recover from a relatively brief period of anesthesia, we have accumulated evidence that neonatal anesthesia can dysregulate epigenetic tags that influence gene transcription such as histone acetylation and DNA methylation. In this review, we briefly summarize the phenomenon of anesthesia-induced developmental neurotoxicity. We then discuss chronic neuropathology caused by neonatal anesthesia, including disturbances in cognition, socio-affective behavior, neuronal morphology, and synaptic plasticity. Finally, we present evidence of anesthesia-induced genetic and epigenetic dysregulation within the developing brain that may be transmitted intergenerationally to anesthesia-naïve offspring.
Identification of LAMA1 mutations ends diagnostic odyssey and has prognostic implications for patients with presumed Joubert syndrome
Authors: Powell Laura , Olinger Eric , Wedderburn Sarah , Ramakumaran Vijayalakshmi Salem , Kini Usha , Clayton-Smith Jill , Ramsden Simon C , Rice Sarah J , Barroso-Gil Miguel , Wilson Ian , Cowley Lorraine , Johnson Sally , Harris Elizabeth , Montgomery Tara , Bertoli Marta ,   Genomics England Research Consortium, Boltshauser Eugen , Sayer John A
Published: July 2021

Paediatric neurology syndromes are a broad and complex group of conditions with a large spectrum of clinical phenotypes. Joubert syndrome is a genetically heterogeneous neurological ciliopathy syndrome with molar tooth sign as the neuroimaging hallmark. We reviewed the clinical, radiological and genetic data for several families with a clinical diagnosis of Joubert syndrome but negative genetic analysis. We detected biallelic pathogenic variants in LAMA1, including novel alleles, in each of the four cases we report, thereby establishing a firm diagnosis of Poretti–Boltshauser syndrome. Analysis of brain MRI revealed cerebellar dysplasia and cerebellar cysts, associated with Poretti–Boltshauser syndrome and the absence of typical molar tooth signs. Using large UK patient cohorts, the relative prevalence of Joubert syndrome as a cause of intellectual disability was 0.2% and of Poretti–Boltshauser syndrome was 0.02%. We conclude that children with congenital brain disorders that mimic Joubert syndrome may have a delayed diagnosis due to poor recognition of key features on brain imaging and the lack of inclusion of LAMA1 on molecular genetic gene panels. We advocate the inclusion of LAMA1 genetic analysis on all intellectual disability and Joubert syndrome gene panels and promote a wider awareness of the clinical and radiological features of these syndromes.
Incarnation, Posthumanism and Performative Anthropology: The Body of Technology and the Body of Christ
Authors: Burdett Michael S
Published: July 2021

This essay argues that a Christian incarnational response to posthumanism must recognize that what is at stake isn't just whether belief systems align. It seeks to relocate the interaction between the church and posthumanism to how the practices of posthumanism and Christianity perform the bodies, affections and dispositions of each. Posthuman practices seeks to habituate: (1) A preference for informational patterns over material instantiation; (2) that consciousness and the self are extended and displaced rather than discrete and localized; (3) that the body is merely a tool, the original prosthesis we learn to manipulate and (4) that human life is organized such that it is seamless with intelligent machines. The Christian performance of embodied life, on the other hand, has Christ as template and, in the Eucharist, Christians are marked by offering, sacrifice and celebration in a community that affirms the integrity of our common incarnate life.
Apixaban vs. warfarin in patients with left ventricular thrombus: a prospective multicentre randomized clinical trial
Authors: Alcalai Ronny , Butnaru Adi , Moravsky Gil , Yagel Oren , Rashad Razek , Ibrahimli Mahsati , Planer David , Amir Offer , Elbaz-Greener Gabby , Leibowitz David
Published: July 2021

Aims

Current guidelines recommend anticoagulation with a vitamin K antagonist to treat left ventricular (LV) thrombus after myocardial infarction (MI). Data on the use of direct oral anticoagulants (DOACs) in this setting are limited. The aim of the study was to assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI.

Methods and results

We conducted a prospective, randomized, multicentre open-label clinical trial including patients with LV thrombus detected by 2D transthoracic echocardiography 1–14 days after acute MI. Thirty-five patients were enrolled in three medical centres; 17 patients were randomized to warfarin and 18 patients to apixaban. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation. Secondary outcomes were major bleeding, stroke or systemic embolism, re-hospitalization, and all-cause mortality. Mean LV thrombus size at enrolment was 18.5 mm × 12.3 mm in the warfarin group and 19.9 mm × 12.4 mm in the apixaban group (P = NS). Thirty-two patients completed 3 months follow-up. In the warfarin group, two patients withdrew, and in the apixaban group one patient died. Thrombus completely resolved in 14 of 15 patients in the warfarin group and in 16 of 17 patients in the apixaban group (P = NS and P = 0.026 for non-inferiority). Two patients had major bleeding in the warfarin group, while no major bleeding events were recorded in the apixaban group. There was one stroke in the warfarin group and one death in the apixaban group.

Conclusion

Our results suggest that apixaban is non-inferior to warfarin for treatment of patients with LV thrombus after acute MI with a 20% non-inferiority margin.
Evidence for a force favoring GC over AT at short intronic sites in Drosophila simulans and Drosophila melanogaster
Authors: Jackson Ben , Charlesworth Brian
Published: July 2021

Population genetics studies often make use of a class of nucleotide site free from selective pressures, in order to make inferences about population size changes or natural selection at other sites. If such neutral sites can be identified, they offer the opportunity to avoid any confounding effects of selection. Here, we investigate evolution at putatively neutrally evolving short intronic sites in natural populations of Drosophila melanogaster and Drosophila simulans, in order to understand the properties of spontaneous mutations and the extent of GC-biased gene conversion in these species. Use of data on the genetics of natural populations is advantageous because it integrates information from large numbers of individuals over long timescales. In agreement with direct evidence from observations of spontaneous mutations in Drosophila, we find a bias in the spectrum of mutations toward AT basepairs. In addition, we find that this bias is stronger in the D. melanogaster lineage than in the D. simulans lineage. The evidence for GC-biased gene conversion in Drosophila has been equivocal. Here, we provide evidence for a weak force favoring GC in both species, which is correlated with the GC content of introns and is stronger in D. simulans than in D. melanogaster.
Distinct Retrotransposon Evolution Profile in the Genome of Rabbit (Oryctolagus cuniculus)
Authors: Yang Naisu , Zhao Bohao , Chen Yang , D’Alessandro Enrico , Chen Cai , Ji Ting , Wu Xinsheng , Song Chengyi
Published: July 2021

Although the rabbit genome has already been annotated, it is mobilome remains largely unknown. Here, multiple pipelines were used to de novo mine and annotate the mobilome in rabbit. Four families and 19 subfamilies of LINE1s, two families and nine subfamilies of SINEs, and 12 ERV families were defined in rabbit based on sequence identity, structural organization, and phylogenetic tree. The analysis of insertion age and polymerase chain reaction suggests that a number of families are very young and may remain active, such as L1B, L1D, OcuSINEA, and OcuERV1. RepeatMasker annotation revealed a distinct transposable element landscape within the genome, with approximately two million copies of SINEs, representing the greatest proportion of the genome (19.61%), followed by LINEs (15.44%), and LTRs (4.11%), respectively, considerably different from most other mammal mobilomes except hedgehog and tree shrew, in which LINEs have the highest proportion. Furthermore, a very high rate of insertion polymorphisms (>85%) for the youngest subfamily (OcuSINEA1) was identified by polymerase chain reaction. The majority of retrotransposon insertions overlapped with protein-coding regions (>80%) and lncRNA (90%) genes. Genomic distribution bias was observed for retrotransposons, with those immediately upstream (−1 kb) and downstream (1 kb) of genes significantly depleted. Local GC content in 50-kb widows had significantly negative correlations with LINE (rs=−0.996) and LTR (rs=−0.829) insertions. The current study revealed a distinct mobilome landscape in rabbit, which will assist in the elucidation of the evolution of the genome of lagomorphs, and even other mammals.
The Drosophila HP1 family is associated with active gene expression across chromatin contexts
Authors: Schoelz John M , Feng Justina X , Riddle Nicole C
Published: July 2021

Drosophila Heterochromatin Protein 1a (HP1a) is essential for heterochromatin formation and is involved in transcriptional silencing. However, certain loci require HP1a to be transcribed. One model posits that HP1a acts as a transcriptional silencer within euchromatin while acting as an activator within heterochromatin. However, HP1a has been observed as an activator of a set of euchromatic genes. Therefore, it is not clear whether, or how, chromatin context informs the function of HP1 proteins. To understand the role of HP1 proteins in transcription, we examined the genome-wide binding profile of HP1a as well as two other Drosophila HP1 family members, HP1B and HP1C, to determine whether coordinated binding of these proteins is associated with specific transcriptional outcomes. We found that HP1 proteins share many of their endogenous binding targets. These genes are marked by active histone modifications and are expressed at higher levels than nontarget genes in both heterochromatin and euchromatin. In addition, HP1 binding targets displayed increased RNA polymerase pausing compared with nontarget genes. Specifically, colocalization of HP1B and HP1C was associated with the highest levels of polymerase pausing and gene expression. Analysis of HP1 null mutants suggests these proteins coordinate activity at transcription start sites to regulate transcription. Depletion of HP1B or HP1C alters expression of protein-coding genes bound by HP1 family members. Our data broaden understanding of the mechanism of transcriptional activation by HP1a and highlight the need to consider particular protein–protein interactions, rather than broader chromatin context, to predict impacts of HP1 at transcription start sites.
Embedding Community-Based Newborn Care in the Ethiopian health system: lessons from a 4-year programme evaluation
Authors: Avan Bilal Iqbal , Berhanu Della , Mekonnen Yirgalem , Beaumont Emma , Tomlin Keith , Allen Elizabeth , Schellenberg Joanna
Published: July 2021

Despite remarkable gains, improving neonatal survival globally remains slow paced. Innovative service-delivery packages have been developed for community health workers (CHWs) to maximize system efficiency and increase the reach of services. However, embedding these in health systems needs structural and procedural alignment. The Community-Based Newborn Care (CBNC) programme was a response to high neonatal mortality in Ethiopia. Key aspects include simplified treatment for neonatal illness, integrated outreach services and task-shifting. Using the CHW functionality model by WHO, this study evaluates the health system response to the programme, including quality of care. A before-and-after study was conducted with three survey time points: baseline (November 2013), midline (December 2015) and follow-up (December 2017—4 years after the programme started). Data were collected at a sample of primary healthcare facilities from 101 districts across four regions. Analysis took two perspectives: (1) health system response, through supplies, infrastructure support and supervision, assessed through interviews and observations at health facilities and (2) quality of care, through CHWs’ theoretical capacity to deliver services, as well as their performance, assessed through functional health literacy and direct observation of young infant case management. Results showed gains in services for young infants, with antibiotics and job aids available at over 90% of health centres. However, services at health posts remained inadequate in 2017. In terms of quality of care, only 37% of CHWs correctly diagnosed key conditions in sick young infants at midline. CHWs’ functional health literacy declined by over 70% in basic aspects of case management during the study. Although the frequency of quarterly supportive supervision visits was above 80% during 2013–2017, visits lacked support for managing sick young infants. Infrastructure and resources improved over the course of the CBNC programme implementation. However, embedding and scaling up the programme lacked the systems-thinking and attention to health system building-blocks needed to optimize service delivery.
Pre-exposure prophylaxis for transgender women and men who have sex with men: qualitative insights from healthcare providers, community organization–based leadership and end users in coastal Kenya
Authors: Kimani Makobu , Sanders Eduard J , Chirro Oscar , Mukuria Nana , Mahmoud Shally , Rinke de Wit Tobias F , Graham Susan M , Operario Don , van der Elst Elise M
Published: July 2021

Transgender women (TW) and men who have sex with men (MSM) in Kenya are disproportionately affected by human immunodeficiency virus (HIV) and would benefit substantially from pre-exposure prophylaxis (PrEP). We conducted focus group discussions (FGDs) with healthcare providers (HCPs) and TW/MSM leadership and in-depth interviews (IDIs) with PrEP-experienced MSM and TW to learn about perceived and actual barriers to PrEP programming. Eleven HCP and 10 TW/MSM leaders participated in FGDs before PrEP roll-out (January 2018) and 12 months later. Nineteen PrEP end-users (11 MSM and 8 TW) participated in IDIs. Topic guides explored PrEP knowledge, HIV acquisition risk, gender identity, motivation for PrEP uptake and adherence and PrEP-dispensing venue preferences. Braun and Clarke thematic analysis was applied. Four themes emerged: limited preparedness of HCPs to provide PrEP to TW and MSM, varied motivation for PrEP uptake and persistence among end users, lack of recognition of TW by HCPs and suggestions for PrEP programming improvement from all stakeholders. Providers’ reluctance to prescribe PrEP to TW and distrust of TW towards providers calls for interventions to improve the capacity of service environments and staff HIV preventive care. Alternative locations for PrEP provision, including community-based sites, may be developed with TW/MSM leaders.
Ciprofloxacin population pharmacokinetics during long-term treatment of osteoarticular infections
Authors: Zahr Noël , Urien Saik , Aubry Alexandra , Chauvin Charlotte , Comets Emmanuelle , Llopis Benoit , Tissot Nadine , Noe Gaëlle , Fourniols Eric , Jaureguiberry Stéphane , Bleibtreu Alexandre , Funck-Brentano Christian ,   the Centre de Référence pour le traitement des Infections Ostéo-Articulaires Complexes (CRIOAC) Pitié-Salpêtrière Hospital, Barrut Nicolas , Bonnet Isabelle , Calin Ruxandra , Caumes Eric , Clarençon Frédéric , Daas Georges , Fautrel Bruno , Fustier Anne , Gandjbakhch Frédérique , Haddad Elie , Khiami Frédéric , Lazennec Jean Yves , Marchant Maxime , Mercy Guillaume , Metz Carole , Miu Mihaela , Mitrovic Stéphane , Monsel Gentiane , Monzani Quentin , Reubrecht Vanessa , Robert Jérôme
Published: July 2021

Background

Ciprofloxacin is an antibiotic used in osteoarticular infections owing to its very good bone penetration. Very few pharmacokinetic data are available in this population.

Objectives

To investigate oral ciprofloxacin population pharmacokinetics in adult patients treated for osteoarticular infections and propose guidance for more effective dosing.

Methods

A retrospective population-pharmacokinetic analysis was performed on 92 consecutive hospitalized patients in the orthopaedic department. Ciprofloxacin plasma samples were obtained on one or two occasions during treatment. Plasma concentration was measured using ultra-performance liquid chromatography system coupled with tandem mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2019R2.

Results

A total of 397 plasma samples were obtained with 11.5% and 41.6% of patients being below the therapeutic target for Gram-negative and staphylococcal infections, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model with a first-order absorption. Ciprofloxacin apparent plasma clearances and volumes of distribution were dependent on patients’ fat-free mass according to the allometric rule. Elimination clearance was also positively related to renal function through the modification of diet in renal disease equation (MDRD) and rifampicin co-administration. When patients are co-treated with rifampicin, ciprofloxacin dosage should be increased by 50% to 60%.

Conclusions

This study showed that free-fat mass was a better size predictor than total body weight for ciprofloxacin clearance and volumes terms. Moreover, both MDRD and rifampicin status were significant predictors of individual ciprofloxacin clearance. Our study suggests that individual adjustment of ciprofloxacin dose in osteoarticular infections with less-susceptible bacteria might be indicated to reach required efficacy targets.
Learning decision thresholds for risk stratification models from aggregate clinician behavior
Authors: Patel Birju S , Steinberg Ethan , Pfohl Stephen R , Shah Nigam H
Published: July 2021

Using a risk stratification model to guide clinical practice often requires the choice of a cutoff—called the decision threshold—on the model’s output to trigger a subsequent action such as an electronic alert. Choosing this cutoff is not always straightforward. We propose a flexible approach that leverages the collective information in treatment decisions made in real life to learn reference decision thresholds from physician practice. Using the example of prescribing a statin for primary prevention of cardiovascular disease based on 10-year risk calculated by the 2013 pooled cohort equations, we demonstrate the feasibility of using real-world data to learn the implicit decision threshold that reflects existing physician behavior. Learning a decision threshold in this manner allows for evaluation of a proposed operating point against the threshold reflective of the community standard of care. Furthermore, this approach can be used to monitor and audit model-guided clinical decision making following model deployment.
A theory-based meta-regression of factors influencing clinical decision support adoption and implementation
Authors: Liu Siru , Reese Thomas J , Kawamoto Kensaku , Del Fiol Guilherme , Weir Charlene
Published: July 2021

Objective

The purpose of the study was to explore the theoretical underpinnings of effective clinical decision support (CDS) factors using the comparative effectiveness results.

Materials and Methods

We leveraged search results from a previous systematic literature review and updated the search to screen articles published from January 2017 to January 2020. We included randomized controlled trials and cluster randomized controlled trials that compared a CDS intervention with and without specific factors. We used random effects meta-regression procedures to analyze clinician behavior for the aggregate effects. The theoretical model was the Unified Theory of Acceptance and Use of Technology (UTAUT) model with motivational control.

Results

Thirty-four studies were included. The meta-regression models identified the importance of effort expectancy (estimated coefficient = −0.162; P = .0003); facilitating conditions (estimated coefficient = 0.094; P = .013); and performance expectancy with motivational control (estimated coefficient = 1.029; P = .022). Each of these factors created a significant impact on clinician behavior. The meta-regression model with the multivariate analysis explained a large amount of the heterogeneity across studies (R2 = 88.32%).

Discussion

Three positive factors were identified: low effort to use, low controllability, and providing more infrastructure and implementation strategies to support the CDS. The multivariate analysis suggests that passive CDS could be effective if users believe the CDS is useful and/or social expectations to use the CDS intervention exist.

Conclusions

Overall, a modified UTAUT model that includes motivational control is an appropriate model to understand psychological factors associated with CDS effectiveness and to guide CDS design, implementation, and optimization.
Tracing the NGLY1 footprints: insights from Drosophila
Authors: Pandey Ashutosh , Jafar-Nejad Hamed
Published: July 2021

Recessive mutations in human N-glycanase 1 (NGLY1) cause a multisystem disorder with various phenotypes including global developmental delay. One of the models utilized to understand the biology of NGLY1 and the pathophysiology of NGLY1 deficiency is Drosophila melanogaster, a well-established, genetically tractable organism broadly used to study various biological processes and human diseases. Loss of the Drosophila NGLY1 homolog (Pngl) causes a host of phenotypes including developmental delay and lethality. Phenotypic, transcriptomic and genome-wide association analyses on Drosophila have revealed links between NGLY1 and several critical developmental and cellular pathways/processes. Further, repurposing screens of Food and Drug Administration (FDA)-approved drugs have identified potential candidates to ameliorate some of the Pngl-mutant phenotypes. Here, we will summarize the insights gained into the functions of NGLY1 from Drosophila studies. We hope that the current review article will encourage additional studies in Drosophila and other model systems towards establishing a therapeutic strategy for NGLY1 deficiency patients.
C-Reactive Protein, Interleukin-6, and Procalcitonin in Diagnosis of Late-Onset Bloodstream Infection in Very Preterm Infants
Authors: Berka Ivan , Korček Peter , Straňák Zbyněk
Published: July 2021

Background

Late-onset bloodstream infection (LOBSI) is common in very preterm infants. Early and accurate diagnosis is crucial for prognosis and outcome. We aimed to analyze the accuracy of routinely used inflammatory biomarkers in the diagnosis of LOBSI as compared to uninfected controls.

Methods

In this single-center, retrospective case-control study, interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) were routinely measured, when infection was clinically suspected. The definition of LOBSI was based on positive blood culture, clinical signs of infection, and onset more than 72 hours after birth.

Results

Among 285 enrolled infants, 66 developed LOBSI. IL-6 was superior to other markers, and levels greater than 100 ng/L had a sensitivity of 94% and a specificity of 99% for the presence of LOBSI. Receiver operating characteristic curve of IL-6 had area under the curve of 0.988 (95% CI = 0.975-1.00, P < .001). The negative predictive value of IL-6, CRP, and PCT for optimal cutoff values was 99%, 95%, and 93%, respectively. The logistic regression model of IL-6 > 100 ng/L or CRP > 10 mg/L were successfully predicted LOBSI in 97.9% of cases.

Conclusions

The combination of IL-6 and CRP seems to have great potential in routine rapid diagnosis of LOBSI development. High negative predictive value of all tested markers could encourage the early discontinuation of antibiotic treatment.
Peritoneal defect herniation causing small bowel obstruction: a rare complication of transabdominal preperitoneal repair
Authors: Hannan Enda , Baird Olivia , Feeney Meghan , Condon Eoghan
Published: July 2021

Laparoscopic approaches to inguinal hernia repair are becoming increasingly more popular as they offer many advantages to open techniques including faster recovery and lower rates of wound infection. However, it is important to recognize complications associated with newer techniques which only become apparent with increased volume and experience. In this report, we describe a rare case of small bowel obstruction (SBO) secondary to peritoneal defect herniation post-transabdominal preperitoneal repair (TAPP). This is an uncommon complication that is sparsely reported in the literature but may have devastating consequences for the patient if unrecognized or mistakenly attributed to adhesional SBO. A high index of suspicion for internal herniation and a low index for reoperation are important with SBO in the early postoperative phase post-TAPP.
Steps and traces
Authors: Rot Jurriaan , Jacobs Bart , Levy Paul Blain
Published: July 2021

In the theory of coalgebras, trace semantics can be defined in various distinct ways, including through algebraic logics, the Kleisli category of a monad or its Eilenberg–Moore category. This paper elaborates two new unifying ideas: (i) coalgebraic,draftrules trace semantics is naturally presented in terms of corecursive algebras, and (ii) all three approaches arise as instances of the same abstract setting. Our perspective puts the different approaches under a common roof and allows to derive conditions under which some of them coincide.
Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa
Authors: Alosaimy Sara , Lagnf Abdalhamid M , Morrisette Taylor , Scipione Marco R , Zhao Jing J , Jorgensen Sarah C J , Mynatt Ryan , Carlson Travis J , Jo Jinhee , Garey Kevin W , Allen David , DeRonde Kailynn , Vega Ana D , Abbo Lilian M , Venugopalan Veena , Athans Vasilios , Saw Stephen , Claeys Kimberly C , Miller Mathew , Molina Kyle C , Veve Michael , Kufel Wesley D , Amaya Lee , Yost Christine , Ortwine Jessica , Davis Susan L , Rybak Michael J
Published: July 2021

Background

We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE).

Methods

This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR).

Results

Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081–0.941).

Conclusions

Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs.
A co-fractionation mass spectrometry-based prediction of protein complex assemblies in the developing rice aleurone-subaleurone
Authors: Lee Youngwoo , Okita Thomas W. , Szymanski Daniel B.
Published: July 2021

Multiprotein complexes execute and coordinate diverse cellular processes such as organelle biogenesis, vesicle trafficking, cell signaling, and metabolism. Knowledge about their composition and localization provides useful clues about the mechanisms of cellular homeostasis and system-level control. This is of great biological importance and practical significance in heterotrophic rice (Oryza sativa) endosperm and aleurone–subaleurone tissues, which are a primary source of seed vitamins and stored energy. Dozens of protein complexes have been implicated in the synthesis, transport, and storage of seed proteins, lipids, vitamins, and minerals. Mutations in protein complexes that control RNA transport result in aberrant endosperm with shrunken and floury phenotypes, significantly reducing seed yield and quality. The purpose of this study was to broadly predict protein complex composition in the aleurone–subaleurone layers of developing rice seeds using co-fractionation mass spectrometry. Following orthogonal chromatographic separations of biological replicates, thousands of protein elution profiles were subjected to distance-based clustering to enable large-scale multimerization state measurements and protein complex predictions. The predicted complexes had predicted functions across diverse functional categories, including novel heteromeric RNA binding protein complexes that may influence seed quality. This effective and open-ended proteomics pipeline provides useful clues about system-level posttranslational control during the early stages of rice seed development.
COMPASS functions as a module of the INO80 chromatin remodeling complex to mediate histone H3K4 methylation in Arabidopsis
Authors: Shang Ji-Yun , Lu Yu-Jia , Cai Xue-Wei , Su Yin-Na , Feng Chao , Li Lin , Chen She , He Xin-Jian
Published: July 2021

In the INO80 chromatin remodeling complex, all of the accessory subunits are assembled on the following three domains of INO80: N-terminal domain (NTD), HSA domain, and ATPase domain. Although the ATPase and HSA domains and their interacting accessory subunits are known to be responsible for chromatin remodeling, it is largely unknown how the accessory subunits that interact with the INO80 NTD regulate chromatin status. Here, we identify both conserved and nonconserved accessory subunits that interact with the three domains in the INO80 complex in Arabidopsis thaliana. While the accessory subunits that interact with all the three INO80 domains can mediate transcriptional repression, the INO80 NTD and the accessory subunits interact with it can contribute to transcriptional activation even when the ATPase domain is absent, suggesting that INO80 has an ATPase-independent role. A subclass of the COMPASS histone H3K4 methyltransferase complexes interact with the INO80 NTD in the INO80 complex and function together with the other accessory subunits that interact with the INO80 NTD, thereby facilitating H3K4 trimethylation and transcriptional activation. This study suggests that the opposite effects of the INO80 complex on transcription are required for the balance between vegetative growth and flowering under diverse environmental conditions.
Large-scale field phenotyping using backpack LiDAR and CropQuant-3D to measure structural variation in wheat
Authors: Zhu Yulei , Sun Gang , Ding Guohui , Zhou Jie , Wen Mingxing , Jin Shichao , Zhao Qiang , Colmer Joshua , Ding Yanfeng , Ober Eric S. , Zhou Ji
Published: July 2021

Plant phenomics bridges the gap between traits of agricultural importance and genomic information. Limitations of current field-based phenotyping solutions include mobility, affordability, throughput, accuracy, scalability, and the ability to analyze big data collected. Here, we present a large-scale phenotyping solution that combines a commercial backpack Light Detection and Ranging (LiDAR) device and our analytic software, CropQuant-3D, which have been applied jointly to phenotype wheat (Triticum aestivum) and associated 3D trait analysis. The use of LiDAR can acquire millions of 3D points to represent spatial features of crops, and CropQuant-3D can extract meaningful traits from large, complex point clouds. In a case study examining the response of wheat varieties to three different levels of nitrogen fertilization in field experiments, the combined solution differentiated significant genotype and treatment effects on crop growth and structural variation in the canopy, with strong correlations with manual measurements. Hence, we demonstrate that this system could consistently perform 3D trait analysis at a larger scale and more quickly than heretofore possible and addresses challenges in mobility, throughput, and scalability. To ensure our work could reach non-expert users, we developed an open-source graphical user interface for CropQuant-3D. We, therefore, believe that the combined system is easy-to-use and could be used as a reliable research tool in multi-location phenotyping for both crop research and breeding. Furthermore, together with the fast maturity of LiDAR technologies, the system has the potential for further development in accuracy and affordability, contributing to the resolution of the phenotyping bottleneck and exploiting available genomic resources more effectively.
Thermostable D-amino acid decarboxylases derived from Thermotoga maritima diaminopimelate decarboxylase
Authors: Marjanovic Antonija , Ramírez-Palacios Carlos J , Masman Marcelo F , Drenth Jeroen , Otzen Marleen , Marrink Siewert-Jan , Janssen Dick B
Published: July 2021

Diaminopimelate decarboxylases (DAPDCs) are highly selective enzymes that catalyze the common final step in different lysine biosynthetic pathways, i.e. the conversion of meso-diaminopimelate (DAP) to L-lysine. We examined the modification of the substrate specificity of the thermostable decarboxylase from Thermotoga maritima with the aim to introduce activity with 2-aminopimelic acid (2-APA) since its decarboxylation leads to 6-aminocaproic acid (6-ACA), a building block for the synthesis of nylon-6. Structure-based mutagenesis of the distal carboxylate binding site resulted in a set of enzyme variants with new activities toward different D-amino acids. One of the mutants (E315T) had lost most of its activity toward DAP and primarily acted as a 2-APA decarboxylase. We next used computational modeling to explain the observed shift in catalytic activities of the mutants. The results suggest that predictive computational protocols can support the redesign of the catalytic properties of this class of decarboxylating PLP-dependent enzymes.
Managing Households’ Expectations with Unconventional Policies
Authors: D’Acunto Francesco , Hoang Daniel , Weber Michael
Published: July 2021

Binding lower bounds on interest rates and large government deficits limit the scope of fiscal and monetary policies to stimulate households’ spending through financial intermediaries and firms. Policy makers have thus been implementing unconventional policies that aim to increase households’ spending directly through managing their expectations. We first show theoretically and empirically that higher inflation expectations increase households’ consumption. We then design a difference-in-differences strategy to assess the effectiveness of unconventional fiscal policy and forward guidance, both of which aim to raise aggregate demand via managing expectations. Whereas unconventional fiscal policy increases households’ expectations and spending, forward guidance announcements do not
LEVELS OF NATURAL AND ANTHROPOGENIC RADIONUCLIDES IN SEDIMENTS OF SOME MOROCCAN COASTAL AREAS AND DOSE ASSESSMENT BASED ON ERICA TOOL
Authors: Ait Bouh H , Laissaoui A , Ziad N , El Kotbi M C , Benmhammed A
Published: July 2021

In this work, we considered the concentrations of natural and anthropogenic radionuclides (namely the 40K, 210Pb, 226Ra, 137Cs, 234Th, 228Th and 228Ra) in sediments from Moroccan coast areas by considering estuaries (Sebou and Loukkos) and marine ecosystems (M’diq Bay and three Lagoons: Moulay Bousselham, Sidi Moussa and Oualidia). Sediment samples were analyzed using Gamma spectrometry. The objective was to establish radioactivity levels in Moroccan coastal areas as well as radiological risk assessment by using the ERICA tool. The software allows the estimation of dose rates to biota (a set of reference organisms by default). The highest activity concentrations were found in sediment samples of Sidi Moussa Lagoon, possibly due to the anthropogenic activities, while the lowest levels were reported in Sebou estuary, attributed most probably to a flooding event that occurred in the same year of sampling. Also, 210Pb and 40K have the most significant concentrations, while 137Cs has the lowest concentrations with a great resemblance with similar works. The World Wide Average concentration of 226Ra was exceeded in the three lagoons and that of 40K only exceeded at Sidi Moussa Lagoon. The application of ERICA tool allowed the assessment of total dose rates that are mainly due to internal exposure with strong contribution of 226Ra mainly for phytoplankton in the case of marine ecosystems and insect larvae, mollusc-bivalve, mollusc-gastropod and zooplankton for estuary ecosystems. The total dose rates were far lesser than the admissible dose rate proposed by ERICA tool (10 μGy h−1) and, therefore, unlikely to cause harmful effects to organisms.
Biopsychosocial Predictors of Depression and Anxiety Symptoms among First-Generation Black African Immigrants
Authors: Saasa Sherinah , Miller Selina
Published: July 2021

Few studies examine factors associated with mental health distress among immigrants from African countries. Using cross-sectional data from first-generation Black African immigrants across the United States (N = 180), this study examined biopsychosocial factors that influence depression and anxiety symptoms among African immigrants in the United States. Ordinary least squares regression was conducted to analyze the data. Approximately 22 percent of the sample reported depression and anxiety symptoms in the moderate to severe range. Results indicated that being male, substance use, discrimination, and loneliness were significantly associated with worse depression and anxiety symptoms. In addition, worries about safety and financial strain were associated with increased mental health distress. Loneliness also moderated the association between discrimination and depression and anxiety symptoms. Findings imply that relational interventions in direct practice settings may play a critical role in helping African immigrants ameliorate depression and anxiety symptoms. This study supports the use of the biopsychosocial approach in assessment and intervention of mental health symptoms as well as a systems approach when understanding the experiences of African immigrants.
Characterization of the Powdery Mildew Resistance Gene in Wheat Breeding Line KN0816 and Its Evaluation in Marker-Assisted Selection
Authors: Wang Wenrui , He Huagang , Gao Huiming , Xu Hongxing , Song Wenyue , Zhang Xu , Zhang Lipei , Song Jiancheng , Liu Cheng , Liu Kaichang , Ma Pengtao
Published: July 2021

Wheat powdery mildew, caused by Blumeria graminis (DC.) Speer f. sp. tritici is a destructive disease seriously threatening yield and quality of common wheat (Triticum aestivum L., 2n=6x=42, AABBDD). Characterization of resistance genes against powdery mildew is useful in parental selection and for developing disease-resistant cultivars. Chinese wheat breeding line KN0816 has superior agronomic performance and resistance to powdery mildew at all growth stages. Genetic analysis using populations of KN0816 crossed with different susceptible parents indicated that a single dominant gene, tentatively designated PmKN0816, conferred seedling resistance to different B. graminis f. sp. tritici isolates. Using a bulked segregant analysis, PmKN0816 was mapped to the Pm6 interval on chromosome arm 2BL using polymorphic markers linked to the cataloged genes Pm6, Pm52, and Pm64, and flanked by the markers CISSR02g-6 and CIT02g-2, both with genetic distances of 0.7 cM. Analysis of closely linked molecular markers indicated that the marker alleles of PmKN0816 differed from those of other powdery mildew resistance genes on 2BL, including Pm6, Pm33, Pm51, Pm64, and PmQ. Based on the genetic and physical locations and response pattern to different B. graminis f. sp. tritici isolates, PmKN0816 is most likely a new powdery mildew resistance gene and possesses effective resistance to all the 14 tested B. graminis f. sp. tritici isolates. In view of the elite agronomic performance of KN0816 combined with the resistance, PmKN0816 is expected to become a valuable resistance gene in wheat breeding. To transfer PmKN0816 to different genetic backgrounds using marker-assisted selection (MAS), closely linked markers of PmKN0816 were evaluated, and four of them (CIT02g-2, CISSR02g-6, CIT02g-10, and CIT02g-17) were confirmed to be applicable for MAS in different genetic backgrounds.
Comparing Pressure Injury Incidence Based on Repositioning Intervals and Support Surfaces in Acute Care Settings: A Quasi-Experimental Pragmatic Study
Authors: Choi Jeong Sil , Hyun Seon Young , Chang Sun Ju
Published: July 2021

OBJECTIVE

To compare pressure injury (PI) incidence based on repositioning intervals and support surfaces in acute care settings.

METHODS

This pragmatic, quasi-experimental trial recruited a total of 251 critically ill patients who were at low or moderate risk for PI development. Participants were assigned to three interventions: a 2-hour repositioning interval using an air mattress, a 2-hour repositioning interval using a foam mattress, or a 3-hour repositioning interval using a foam mattress. Data were collected by nurses every shift over the course of 14 days. Pressure injury incidence was analyzed using a χ
2 test.

RESULTS

There were no statistically significant differences in PI incidence between the groups with a 2-hour repositioning interval. However, the PI incidence in the group using a foam mattress with a 3-hour repositioning interval was significantly lower than in the group using an air mattress with a 2-hour repositioning interval (odds ratio, 0.481; 95% confidence interval, 0.410–0.565).

CONCLUSIONS

The findings showed that PIs decreased when the repositioning interval was extended from every 2 hours to every 3 hours while using foam mattresses. This study suggests that a 3-hour repositioning interval using a foam mattress could be applied to reduce the risk of PI development for patients at low or moderate risk.