bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Efficacy of Patients With Secondary Bacteremia Treated With Omadacycline: Results From Phase 3 Acute Bacterial Skin and Skin Structure Infections and Community-Acquired Bacterial Pneumonia Studies
Authors: Sakoulas George , Eckburg Paul B , Amodio-Groton Maria , Manley Amy , Tzanis Evan , Das Anita F , Noble Robert , McGovern Paul C
Published: June 2021

In this post hoc analysis of the 63 patients with secondary bacteremia enrolled in the 3 omadacycline phase 3 studies of acute bacterial skin/skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP), we determined that omadacycline is a viable therapeutic option for appropriate patients with secondary bacteremia.
Painless loss of vision: rapid diagnosis of a central retinal artery occlusion utilizing point-of-care ultrasound
Authors: Taylor Gregory M , Evans Daniel , Doggette Robert P , Wallace Ryan C , Flack Andrew T , Kennedy Sarah K
Published: June 2021

Point-of-care ultrasound (POCUS) has become an essential part of the evaluation of vision loss among emergency physicians in the emergency department (ED). It is frequently used to evaluate for vitreous hemorrhage, foreign bodies, retinal detachment, optic neuritis and posterior vitreous detachment; however, it can also be used to evaluate for a central retinal artery occlusion (CRAO). A POCUS can reveal a hyperechoic density in the optic nerve sheath just proximal to the retinal surface, and this is referred to as a retrobulbar ‘spot sign’ (RBSS). We present the case of an 88-year-old male that presented to our community ED with a painless loss of vision to his right eye. A POCUS revealed an RBSS of the central retinal artery and he was subsequently diagnosed with a CRAO. At his 1-month follow-up, he has regained light perception and 15% of his vision, however, remains with significant visual impairment.
Back to basics: a rare and aggressive case of Aggregatibacter aphrophilus endocarditis
Authors: Al-Sakini Nada , Bruce Charo , Seitler Samuel , Ibrahim Wasyla , Nicholas Victoria , Loup Orphelie , Shore Darryl , Li Wei , Gatzoulis Michael A
Published: June 2021

We present the case of a 25-year-old with a history of bicuspid aortic valve and ascending aortopathy who was successfully treated for infective endocarditis (IE) due to Aggregatibacter aphrophilus. His clinical course was complicated by a large aortic root abscess not initially visualised on transthoracic echocardiography or computerised tomography. The cardinal feature of progressive prolongation of the PR interval on serial electrocardiograms was the only sign associated with clinical deterioration and was the trigger for rapid investigation and urgent management. Our case emphasises the importance of simple bedside tests to identify dynamic clinical scenarios and the requirement for early further imaging in the management of IE.
A case of macrophage activation syndrome in a patient with anti-synthetase syndrome
Authors: Ahmad Nadia , Parmar Aneel , Kitchen Joanne
Published: June 2021

Anti-synthetase syndrome (ASS) is an autoimmune disease characterized by autoantibodies against an aminoacyl transfer RNA synthetase with clinical features including interstitial lung disease, non-erosive arthritis, myositis, Raynaud’s phenomenon, unexplained fever and/or mechanic’s hands. Macrophage activation syndrome (MAS) is a potentially fatal hyper- inflammatory syndrome that can occur as a complication of systemic rheumatic diseases. However, the association of MAS and ASS has rarely been reported in the literature. Here, we report this association in a patient with overlap ASS and anti-CCP positive rheumatoid arthritis. First line management with steroids was complicated by diabetic ketoacidosis, hence requiring use of anti-IL1 therapy (anakinra) for disease control.
Breaking Down the Walls
Authors: Stockhausen Ulrike Elisabeth
Published: June 2021

This chapter traces the results of evangelical immigration activism, covering the years between 2009 and 2014. By proposing a concept based both on justice and on compassion, evangelical immigration activists resurrected the biblical teachings to care for the “stranger” and reshaped the theology of hospitality in order to meet evangelical concerns about the rule of law. The chapter highlights the crucial role that Latinx evangelical leaders played in placing immigration on the evangelical agenda. They were joined by evangelical leaders who brought a renewed focus on social justice into their organizations. They came together in the Evangelical Immigration Table, a group founded in 2012, which hoped to change both evangelical immigration attitudes and immigration policy at the national level. The results of their activism are mixed: while surveys showed increasing evangelical support for immigration reform that includes a pathway to citizenship, this support failed to translate into electoral choices.
‘Pandemic within a pandemic’: a call to end police brutality
Authors: Corpuz Jeff Clyde G
Published: June 2021

This correspondence points out the excessive use of police force in the Philippines since the outbreak of the pandemic. In a recent correspondence, the authors called for a cooperative, honest and considerate attitude toward the government. However, how can one trust the government if it relies heavily on draconian measures in ‘war’ against the pandemic?
Ultrasound of shoulder and knee improves the accuracy of the 2012 EULAR/ACR provisional classification criteria for polymyalgia rheumatica
Authors: Kobayashi Kei , Nakagomi Daiki , Kobayashi Yoshiaki , Ajima Chisaki , Hanai Shunichiro , Koyama Kensuke , Ikeda Kei
Published: June 2021

Objective

Recent studies suggest that the knee is frequently involved in PMR. In this study, we aimed to determine whether the US assessment of the shoulder and knee discriminates between PMR and other differential diagnoses and improves the accuracy of the 2012 EULAR/ACR provisional classification criteria for PMR.

Methods

We consecutively enrolled 81 untreated patients who received a diagnosis of PMR. These patients were divided into two groups based on the final diagnosis made at 1-year follow-up: PMR-definite group (n = 60) and PMR-mimic group (n = 21). We also enrolled age/sex-matched untreated RA patients with shoulder pain from an independent cohort (RA group, n = 60). All patients underwent comprehensive US assessment of the shoulder and knee for synovitis, bursitis, tenosynovitis, tendinitis and ligament inflammation at baseline.

Results

US scores for tenosynovitis, tendinitis and ligament inflammation better discriminated the PMR-definite group from the PMR-mimic and RA groups than do those for synovitis or bursitis. Among logistic regression models to identify US variables that were associated with the PMR-definite group, the best fitted model included two US variables: the bilateral involvement of the shoulder (long head of biceps, supraspinatus or subscapularis tendon) and the bilateral involvement of the knee (popliteus tendon or medial or lateral collateral ligament). Incorporating these two items into the 2012 EULAR/ACR provisional classification criteria numerically increased the accuracy to classify the PMR-definite group.

Conclusion

US assessment of the tendon/ligament-related lesions in the shoulder and knee may improve the accuracy of the 2012 EULAR/ACR provisional classification criteria for PMR.
All-cause and cause-specific mortality in patients with giant cell arteritis: a nationwide, population-based cohort study
Authors: Therkildsen Philip , Nielsen Berit Dalsgaard , de Thurah Annette , Hansen Ib Tønder , Nørgaard Mette , Hauge Ellen-Margrethe
Published: June 2021

Objectives

To investigate whether GCA is associated with increased all-cause and cause-specific mortality.

Methods

A nationwide, population-based cohort study in Denmark using medical and administrative registries. GCA cases were defined as patients aged ≥50 years from 1996–2018 with a first-time discharge diagnosis of GCA and ≥3 prescriptions for prednisolone within 6 months following diagnosis. Each GCA patient was matched based on age, sex and calendar time to 10 persons without a history of GCA. Index date was the date for the third prednisolone prescription. We used a pseudo-observation approach to calculate all-cause and cause-specific mortality, adjusted risk differences (RDs) and relative risks (RRs).

Results

We included 9908 GCA patients and 98 204 persons from the general population. The median time for GCA patients to redeem the third prednisolone prescription was 74 days [interquartile range (IQR: 49–106)]. Among GCA patients, the overall mortality was 6.4% (95% CI: 5.9, 6.9) 1 year after index date and 45% (95% CI: 44, 47) after 10 years. Compared with the reference cohort, adjusted RDs and RRs of deaths in the GCA cohort were 2.2% (95% CI: 1.7, 2.7) and 1.49 (95% CI: 1.36, 1.64) after 1 year, and 2.1% (95% CI: 1.0, 3.3) and 1.03 (95% CI: 1.00, 1.05) 10 years after index date. GCA patients had a higher risk of death due to infectious, endocrine, cardiovascular and gastrointestinal diseases.

Conclusions

GCA is associated with increased all-cause mortality, particularly within the first year following the diagnosis. Cause-specific mortality indicates that mortality in GCA may in part be due to glucocorticoid-related complications.
VALIDATED MEASUREMENT OF URANIUM IN A HUMAN URINE STANDARD REFERENCE MATERIAL BY ICP-MS WITH THE STANDARD ADDITION METHOD
Authors: Kang Cheolhyun , Lee Jongil , Lee Kwang-Sik
Published: June 2021

The Urine Analysis Laboratory of the Korea Atomic Energy Research Institute has developed an in vitro method for measuring uranium in spot urine samples using inductively coupled plasma-mass spectrometry (ICP-MS) with microwave-assisted digestion and standard addition. To validate this procedure, the frozen human urine standard reference material (SRM 2668), such as uranium and creatinine, were analyzed. To overcome the matrix effect and thereby obtain precise measurement data, the standard addition method with extrapolation of four additional points was applied. The measured values for uranium in the SRM were within the acceptable margin of error. The results were compared and evaluated with respect to the American National Standards Institute and Heath Physics Society (ANSI/HPS) N13.30 and International Organization for Standardization 28218 standards. The relative precision (SBr), relative bias (Br), and root-mean-square error values were within the acceptable ranges for the SRM.
Genomic Sequence Resource of Kabatiella zeae, the Causative Pathogen of Corn Eyespot Disease
Authors: Wang Yafei , Yao Jinai , Xia Xinyao , Li Zhiqiang , Zhou Shaoqun , Liu Wende , Wu Hanxiang
Published: June 2021

Kabatiella zeae is the causative pathogen of corn eyespot disease, which is an important leaf disease that damages corn (Zea mays L.) worldwide. In this study, we provided an annotated draft of the assembled genome of the K. zeae field strain KZ1 through PacBio and Illumina sequencing. The assembled KZ1 genome size is 23,602,820 bp, and its GC content is 50.71%. The completeness of the assembled genome is 97.6% in this study. The assembly obtained in this study has 94 contigs and the length of N50 is 720,243 bp. This study is the first report of the K. zeae genome, which contributes to further research on the genetic variation and pathogenic mechanism of this important fungal pathogen.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Characterization of Aphanomyces euteiches Pathotypes Infecting Peas in Western Canada
Authors: Sivachandra Kumar Nimllash T. , Caudillo-Ruiz Kiela B. , Chatterton Syama , Banniza Sabine
Published: June 2021

Aphanomyces root rot, caused by the soilborne oomycete Aphanomyces euteiches Drechs., has developed into a serious disease in the pea- and lentil-producing areas of the Great Plains of North America. Based on six pea differentials previously used to differentiate 11 pathotypes in France, pathotypes were identified among field isolates from Saskatchewan (14) and Alberta (18). Four isolates from the U.S.A. and standard isolates for pathotypes I and III designated in the French study were also included. Each isolate was tested twice in replicated experiments by inoculating French pea differentials ‘Baccara’, ‘Capella’, MN 313, 902131, 552, and PI 80693, along with the Canadian susceptible pea cultivar ‘CDC Meadow’ and partially resistant USDA line PI 660736 under controlled conditions. Pea plants grown in vermiculite were inoculated 10 days after seeding by pipetting 5 ml of a suspension containing 1 × 103 zoospores ml−1 to the base of each plant. Root discoloration was scored 10 days postinoculation using a 0 to 5 scale. Testing revealed that 38 of the isolates, including standard pathotype I isolate RB84, belonged to pathotype I; four isolates including standard pathotype III isolate Ae109 were pathotype III; and U.S.A. isolate Ae16-01 was a pathotype II isolate. An alfalfa isolate from Quebec was avirulent on all pea genotypes. These findings indicate that pathotype I is predominant on the Canadian prairies.
Discrepancies in Physician and Coroner Findings in Cases of Fatal Suspected Physical Child Abuse
Authors: Arnold Tyler S. , Siekmann Tyler , Thackeray Jonathan D. , Bridge Jeffrey A. , Cohen Daniel M.
Published: June 2021

Objectives

As mandated reporters of suspected abuse, physicians must consider abuse when a child dies unexpectedly. Subsequently, a coroner or medical examiner determines the manner of death (MOD) and cause of death (COD). Accurate diagnoses and determinations are important for social safety and justice. This study described discrepancies between physicians' and coroners' findings in cases of fatal suspected physical child abuse.

Methods

This study was a single-institution, retrospective review. All children 6 years or younger who died in a pediatric emergency department from October 2006 to January 2013 with a coroner report were included in this study. Coroner reports, MODs, and CODs were reviewed. Skeletal survey results were compared with coroners' findings.

Results

One hundred twenty-nine children were included. The MODs included the following: undetermined, 63 (49%); accident, 32 (25%); natural, 31 (24%); and homicide, 3 (2%). Thirty-three (26%) of the 129 patients had abuse suspected at the time of death in the emergency department; in this subset, MODs were as follows: undetermined, 16 (48%); accident, 8 (24%); natural, 6 (18%); and homicide, 3 (9%). Sudden infant death syndrome or sudden unexpected death was the most common COD in all children (68, 55%). Skeletal surveys were positive in 12 children with 29 fractures identified; 8 (28%) of the 29 fractures were corroborated on autopsy findings. Of the 12 children with positive skeletal survey findings, only 1 was ruled a homicide.

Conclusions

We found discrepancies between coroner determination of homicide and abuse suspected by physicians, especially among children with fractures. Improved communication between agencies in cases of fatal child abuse is needed.
Cholesterol Embolization Syndrome After Kidney Transplantation: A Case Series and Systematic Review
Authors: Francke Marith I. , Clahsen-van Groningen Marian C. , van den Bosch Thierry P. P. , Becker Jan U. , Hesselink Dennis A.
Published: June 2021

Background.

Cholesterol embolization syndrome (CES) is an uncommon but well-known cause of renal failure in native kidneys, but little is known about CES in kidney transplant recipients. The aim of this study was to determine the incidence, clinical characteristics, histopathology, and prognosis of CES after kidney transplantation.

Methods.

CES cases in both transplanted and native kidneys (control group) were identified by searching the databases of the divisions of Nephrology and Pathology of our institution. Clinical data were retrospectively collected. Biopsies were classified according to the latest Banff 2019 Update. Second, a systematic literature search was performed (December 01, 2020) of Ovid MEDLINE, EMBASE, the Cochrane Central Register of controlled trials, Google Scholar, and Web of Science.

Results.

CES was observed in for-cause biopsies of 11 out of 2350 (0.47%) kidney transplant recipients transplanted between January 1, 2006, and December 31, 2018 (0.0009 cases per person-year). All patients had ≥1 cardiovascular risk factor, and 9 donors were expanded criteria donors. Graft loss occurred in 27.3% of the patients diagnosed with CES. Eight transplant biopsies with CES were also classified as biopsy-proven acute rejection. Transplant biopsies showed signs of inflammation (arteritis, n = 7; interstitial inflammation, n = 5; tubulitis, n = 7). One patient with CES in a native kidney was identified. The biopsy of the native kidney only showed arteritis and classified as an isolated “v” lesion. The literature search resulted in 188 unique articles of which 20 were included. A total of 47 cases of CES after kidney transplantation was reported. Cholesterol emboli were found in <1% of all kidney transplant biopsies. In 57.8% of the kidney transplant biopsies with CES described in literature, concomitant inflammation was present.

Conclusions.

CES is an uncommon cause of kidney transplant failure, although the incidence of CES may be underestimated. CES may mimic rejection as it can be accompanied by arteritis.
Machine Perfusion of Donation After Circulatory Death Liver and Lungs Before Combined Liver-lung Transplantation
Authors: van Leeuwen Otto B. , Brüggenwirth Isabel M.A. , de Kleine Ruben H.J. , van den Berg Aad P. , Verschuuren Erik A.M. , Erasmus Michiel E. , Porte Robert J.
Published: June 2021

Shortage of deceased donor organs for transplantation has led to the increased use of organs from donation after circulatory death (DCD) donors. There are currently no reports describing outcomes after multiorgan transplantation with DCD livers. The use of DCD organs for multiorgan transplantation can be enhanced if the detrimental effects of prolonged cold ischemia and subsequent ischemia-reperfusion injury are overcome. We present a case in which the liver and lungs of a DCD donor were preserved using ex situ machine perfusion for combined liver-lung transplantation. The recipient was a 19-year-old male patient requiring bilateral lung transplantation for severe progressive pleural parenchymal fibroelastosis and portal hypertension with portal vein thrombosis. The donor liver was preserved with dual hypothermic oxygenated machine perfusion, whereas the lungs were perfused using ex vivo lung perfusion. With ex vivo lung perfusion, total preservation time of right and left lung reached 17 and 21 h, respectively. Now, 2 y after transplantation, liver function is normal and lung function is improving. To conclude, we suggest that combined transplantation of DCD liver and lungs is feasible when cold ischemia is reduced with ex situ machine perfusion preservation.
Sonographic Reference Values of Vagus Nerve: A Systematic Review and Meta-analysis
Authors: Abdelnaby Ramy , Elsayed Mohamed , Mohamed Khaled A. , Dardeer Khaled T. , Sonbol Yousef Tarek , ELgenidy Anas , Barakat Mahmoud H. , NasrEldin Yasmin K. , Maier Andrea
Published: June 2021

Purpose:

To establish the first comprehensive and standardized set of vagus nerve (VN) sonographic reference values across all the published studies that can be used to standardize and guide clinical practice and research.

Methods:

This systematic review includes all possible available data from a total of 27 studies and 21 of them were included in the meta-analysis having a total of 864 participants.

Results:

The overall mean cross-sectional area ranged from 2.29 to 2.76 mm2 for the right VN and from 1.83 to 2.23 mm2 for the left VN with 95% confidence interval. Sonographic reference values of VN at common carotid artery bifurcation, thyroid gland, and cartilage as well as other anatomic landmarks were provided.

Conclusions:

The mean cross-sectional area of the right VN of 2.53 mm2 and the left one of 2.03 mm2 can be considered as sonographic reference values in healthy adults. This review provides these reference values to be considered in the further sonographic evaluation of VNs.
Correlation between Pregnancy Status and Severe Corona-Virus Disease Characterized by Cytokine Storm: Systematic Review and Meta-Analysis
Authors: Muthuka John , Kiptoo Michael , Oluoch Kelly , Nyamai Everlyn
Published: June 2021

Background

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SAR2-COV-2) that identified first in Wuhan, China, in December 2019, rapidly spreading to the rest of the globe, becoming a pandemic. Some studies have eluded to an association between pregnancy status and severe COVID-19 cytokine storm, some, in contrast, have demonstrated such. The aim of the current study was to find the relationship between pregnancy status and clinical COVID-19 severity characterized by cytokine storm through a systematic review and meta-analysis approach.

Methods

We searched Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to identify clinical studies suitable for inclusion in this meta-analysis. Studies reporting pregnancy status and comparing the COVID-19 severity cytokine storm outcome were included. The COVID-19 severity characterized by cytokine storm was described using parameters such as; Intensive Care Unit Admission, Invasive Mechanical Ventilation, Mechanical Ventilation, Hospital Admission, Pro and Inflammatory cytokine levels, consolidation on chest CT scan, pulmonary infiltration, extreme fevers as characteristic of cytokine storm, syndromic severity, higher neutrophil count indicative of cytokine storm and severe COVI-19 presentation.

Results

A total of 17 articles detailing 840332 COVID-19 women were included. Our meta-analysis revealed a relationship between positive pregnancy status and severe COVID-19 cytokine storm case (random effect model, OR=2.47; 95% CI: 1.63-3.73; P < 0.0001), with a cumulative incidence of 6432 (14.1%) among the pregnant women with COVID-19 and 24352 (3.1%) among the non-pregnant women with COVI-19. Further to this, we found that the sub-analysis between Single Centre and Multiple Centre studies demonstrated seemingly the same as heterogeneity (I2 = 72 and (I2 = 98), respectively. Sensitivity analysis on each sub-group revealed that pregnancy was significantly related to severe COVID-19 with cytokine storm from single Centre studies, (fixed effect model, OR= 3.97; 95% CI: 2.26-6.95; P< 0.00001) with very low heterogeneity (I2 = 2 %; P = 0.42).

Conclusion

Being pregnant is clearly associated with experiencing a severe COVID-19 characterized by a cytokine storm. The SARS-COV-2 epidemic should serve as an impetus for pregnant women diagnosed with COVID-19, and map out salient risk factors associated with its severity. The trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) CRD42021242011.
Subcutaneous REGEN-COV Antibody Combination for Covid-19 Prevention
Authors: O’Brien Meagan P. , Forleo-Neto Eduardo , Musser Bret J. , Isa Flonza , Chan Kuo-Chen , Sarkar Neena , Bar Katharine J. , Barnabas Ruanne V. , Barouch Dan H. , Cohen Myron S. , Hurt Christopher B. , Burwen Dale R. , Marovich Mary A. , Hou Peijie , Heirman Ingeborg , Davis John D. , Turner Kenneth C. , Ramesh Divya , Mahmood Adnan , Hooper Andrea T. , Hamilton Jennifer D. , Kim Yunji , Purcell Lisa A. , Baum Alina , Kyratsous Christos A. , Krainson James , Perez-Perez Richard , Mohseni Rizwana , Kowal Bari , DiCioccio A. Thomas , Stahl Neil , Lipsich Leah , Braunstein Ned , Herman Gary , Yancopoulos George D. , Weinreich David M. ,   for the Covid-19 Phase 3 Prevention Trial Team
Published: June 2021

Background

Casirivimab and imdevimab (REGEN-COV™) markedly reduces risk of hospitalization or death in high-risk individuals with Covid-19. Here we explore the possibility that subcutaneous REGEN-COV prevents SARS-CoV-2 infection and subsequent Covid-19 in individuals at high risk of contracting SARS-CoV-2 by close exposure in a household with a documented SARS-CoV-2–infected individual.

Methods

Individuals ≥12 years were enrolled within 96 hours of a household contact being diagnosed with SARS-CoV-2 and randomized 1:1 to receive 1200 mg REGEN-COV or placebo via subcutaneous injection. The primary efficacy endpoint was the proportion of participants without evidence of infection (SARS-CoV-2 RT-qPCR– negative) or prior immunity (seronegative) who subsequently developed symptomatic SARS-CoV-2 infection during a 28-day efficacy assessment period.

Results

Subcutaneous REGEN-COV significantly prevented symptomatic SARS-CoV-2 infection compared with placebo (81.4% risk reduction; 11/753 [1.5%] vs. 59/752 [7.8%], respectively; P<0.0001), with 92.6% risk reduction after the first week (2/753 [0.3%] vs. 27/752 [3.6%], respectively). REGEN-COV also prevented overall infections, either symptomatic or asymptomatic (66.4% risk reduction). Among infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV vs. placebo (1.2 vs. 3.2 weeks, respectively), and the duration of time with high viral load (>104 copies/mL) was lower (0.4 vs. 1.3 weeks, respectively). REGEN-COV was generally well tolerated.

Conclusions

Administration of subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in uninfected household contacts of infected individuals. Among individuals who became infected, REGEN-COV reduced the duration of symptomatic disease, decreased maximal viral load, and reduced the duration of detectable virus.

(ClinicalTrials.gov number, NCT04452318.)
Wolbachia-mediated sterility suppressesAedes aegyptipopulations in the urban tropics
Authors:   The Project Wolbachia – Singapore Consortium, Ching Ng Lee
Published: June 2021

Incompatible insect technique (IIT) via releases of maleWolbachia-infected mosquitoes is a promising tool for dengue control. In a three-year trial in Singaporean high-rise housing estates, we demonstrated thatWolbachia-based IIT dramatically reduces both wildtypeAedes aegyptipopulations [reductions of 92.7% (95% CI: 84.7%–95.8%) and 98.3% (97.7%–99.8%)] and dengue incidence [reductions of 71% (43%-87%) to 88% (57%-99%)] in the targeted areas. The study highlights the need to ensure adequate vertical distribution of released males in high-rise buildings, address immigration of wildtype females from neighboring areas, and prevent and mitigate stable establishment ofWolbachiain field mosquito populations. Our results demonstrate the potential ofWolbachia-based IIT (supplemented with irradiation, in Singapore’s context) for strengthening dengue control in tropical cities, where dengue burden is the greatest.

One Sentence Summary

Releases of maleWolbachia-infectedAedes aegyptisuppress dengue mosquitoes and reduce dengue incidence in high-rise urban areas in Singapore.
Respiratory and C4-photosynthetic NAD-malic enzyme coexist in bundle sheath cells mitochondria and evolved via association of differentially adapted subunits
Authors: Hüdig Meike , Tronconi Marcos A. , Zubimendi Juan P. , Sage Tammy L. , Poschmann Gereon , Bickel David , Gohlke Holger , Maurino Veronica G.
Published: June 2021

In different lineages of Cleomaceae, NAD-malic enzyme (NAD-ME) was independently co-opted to participate in C4 photosynthesis. In the C4 Cleome species Gynandropsis gynandra and Cleome angustifolia, all NAD-ME genes (NAD-MEα, NAD-MEβ1, and NAD-MEβ2) were affected by C4 evolution and are expressed at higher levels than their orthologs in the C3 Cleome species Tarenaya hassleriana. In the latter C3 species, the NAD-ME housekeeping function is performed by two heteromers, NAD-MEα/β1 and NAD-MEα/β2, with similar biochemical properties. In both C4 species analyzed, this role is restricted the NAD-MEα/β2 heteromer. In the C4 species, NAD-MEα/β1 is exclusively present in the leaves, where it accounts for most of the enzymatic activity. GgNAD-MEα/β1 exhibits high catalytic efficiency and is differentially activated by the C4 intermediate aspartate, confirming its role as the C4-decarboxylase. During C4 evolution, GgNAD-MEβ1and CaNAD-MEβ1 lost their catalytic activity; their contribution to enzymatic activity results from a stabilizing effect on the associated α-subunit. We conclude that in bundle sheath cell mitochondria of C4 Cleome species, the functions of NAD-ME as C4 photosynthetic decarboxylase and as a tricarboxylic acid cycle-associated housekeeping enzyme coexist and are performed by isoforms that combine the same α subunit with differentially adapted β subunits.
Molnupiravir, an Oral Antiviral Treatment for COVID-19
Authors: Fischer William , Eron Joseph J. , Holman Wayne , Cohen Myron S. , Fang Lei , Szewczyk Laura J. , Sheahan Timothy P , Baric Ralph , Mollan Katie R. , Wolfe Cameron R. , Duke Elizabeth R. , Azizad Masoud M. , Borroto-Esoda Katyna , Wohl David A. , Loftis Amy James , Alabanza Paul , Lipansky Felicia , Painter Wendy P.
Published: June 2021

Background

Easily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 (ClinicalTrials.govNCT04405570).

Methods

Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs.

Results

Among 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups.

Conclusions

Molnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.
Conformational and interface variability of bivalent RNF4-SIM diSUMO3 interaction
Authors: Kötter Alex , Mootz Henning D. , Heuer Andreas
Published: June 2021

SUMO targeted ubiqutin ligases (STUbLs) like RNF4 or Arkadia/RNF111 recognize SUMO chains through multiple SUMO interacting motifs (SIMs). Typically, these are contained in disordered regions of these enzymes and also the individual SUMO domains of SUMO chains move relatively freely. It is assumed that binding the SIM region significantly restricts the conformational freedom of SUMO chains. Here, we present the results of extensive molecular dynamics simulations on the complex formed by the SIM2-SIM3 region of RNF4 and diSUMO3. Though our simulations highlight the importance of typical SIM-SUMO interfaces also in the multivalent situation, we observe that frequently other regions of the peptide than the canonical SIMs establish this interface. This variability regarding the individual interfaces leads to a conformationally highly flexible complex. Even though this is in contrast to previous models of the RNF4 SUMO chain interaction, we demonstrate that our simulations are clearly consistent with previous experimental results.
Alzheimer’s disease-associated P460L mutation in ephrin receptor type A1 (EphA1) leads to dysregulated Rho-GTPase signaling
Authors: Kim Y. , Lasso G. , Patel H. , Vardarajan B. , Santa-Maria I , Lefort R.
Published: June 2021

Recently, late onset AD (LOAD) genome-wide association studies identified EphA1, a member of receptor tyrosine kinase family (RTK) as a disease associated loci. In the follow-up study where 3 independent LOAD cohorts were performed, a P460L coding mutation in EphA1 loci showed a significant association with LOAD. However, the role of EphA1 and P460L mutant EphA1 in AD is not fully understood. We have characterized this mutation biophysically and biochemically. Our structural in silico model and in vitro biochemical analysis demonstrate that EphA1-P460L mutation makes the receptor constitutively active suggesting a gain-of-toxic function leading to chronic EphA1 signaling in the brain. Moreover, we report that the EphA1 P460L variant triggers Rho-GTPase signaling dysregulation that could potentially contribute to spine morphology abnormalities and synaptic dysfunction observed in AD pathology.
Towards more accurate preclinical glioblastoma modelling: reverse translation of clinical standard of care in a glioblastoma mouse model
Authors: Riva Matteo , Bevers Sien , Wouters Roxanne , Thirion Gitte , Vandenbrande Katja , Vankerckhoven Ann , Berckmans Yani , Verbeeck Jelle , De Keersmaecker Kim , Coosemans An
Published: June 2021

Introduction

Contrarily to clinical trials, where glioblastoma (GBM) patients are usually heavily pre-treated (surgery, radiotherapy (RT) and temozolomide (TMZ)) before receiving the experimental therapies, in preclinical GBM studies experimental treatments have mostly been administered as monotherapy or combined with a very limited part of the clinical standard of care. This discrepancy can explain the failed clinical translation of preclinically successful treatments. This study is aimed at evaluating the feasibility and survival impact of the clinical standard of care in glioma-bearing mice. Methods. Neurospheres CT-2A tumor-bearing mice were treated with fluorescence-guided tumor resection, focal RT and oral TMZ.

Results

The implementation of postoperative intensive care treatment reduced surgical mortality by approximately 50% and increased experimental cost-effectiveness. Partial and total tumor resection significantly prolonged survival, the latter showing the strongest effect. Mice treated with surgery combined with RT or with RT and TMZ survived significantly longer than untreated controls.

Conclusions

Implementing the current GBM clinical standard of care in preclinical research is feasible and it leads to results in line with those obtained in patients. Systematic preclinical evaluation of the efficacy of experimental therapies in combination with standard of care treatments could improve the translational impact of next generation GBM animal studies.
Separate physiological roles of specific and non-specific DNA binding of HU protein in Escherichia coli
Authors: Verma Subhash , Adhya Sankar
Published: June 2021

Conserved in bacteria, the histone-like protein HU is crucial for genome organization and expression of many genes. It binds DNA regardless of the sequence and exhibits two binding affinities in vitro, low-affinity to any B-DNA (non-specific) and high-affinity to DNA with distortions like kinks and cruciforms (structure-specific), but the physiological relevance of the two binding modes needed further investigation. We validated and defined the three conserved lysine residues, K3, K18, and K83, in Escherichia coli HU as critical amino acid residues for both non-specific and structure-specific binding and the conserved proline residue P63 additionally for only the structure-specific binding. By mutating these residues in vivo, we showed that two DNA binding modes of HU play separate physiological roles. The DNA structure-specific binding, occurring at specific sites in the E. coli genome, promotes higher-order DNA structure formation, regulating the expression of many genes, including those involved in chromosome maintenance and segregation. The non-specific binding participates in numerous associations of HU with the chromosomal DNA, dictating chromosome structure and organization. Our findings underscore the importance of DNA structure in transcription regulation and promiscuous DNA-protein interactions in a dynamic organization of a bacterial genome.
Vapor mediation as a tool to control micro-nano scale dendritic crystallization and preferential bacterial distribution in drying respiratory droplets
Authors: Hegde Omkar , Chatterjee Ritika , Rasheed Abdur , Chakravortty Dipshikha , Basu Saptarshi
Published: June 2021

Deposits of biofluid droplets on surfaces (such as respiratory droplets formed during an expiratory event fallen on surfaces) are composed of the water-based salt-protein solution that may also contain an infection (bacterial/viral).The final patterns of the deposit formed are dictated by the composition of the fluid and flow dynamics within the droplet. This work reports the spatio-temporal, topological regulation of deposits of respiratory fluid droplets and control of motility of bacteria by tweaking flow inside droplets using non-contact vapor-mediated interactions. When evaporated on a glass surface, respiratory droplets form haphazard multiscale dendritic, cruciform-shaped precipitates—using vapor mediation as a tool to control these deposits at the level of nano-micro-millimeter scales. Wemorphologically control dendrite orientation, size and subsequently suppress cruciform-shaped crystals. The nucleation sites are controlled via preferential transfer of solutes in the droplets; thus, achieving control over crystal occurrence and growth dynamics. The active living matter like bacteria is also preferentially segregated with controlled motility without attenuation of its viability and pathogenesis. For the first time, we have experimentally presented a proof-of-concept to control the motion of live active matter like bacteria in a near non-intrusive manner. The methodology can have ramifications in biomedical applications like disease detection, controlling bacterial motility, and bacterial segregation.
Teaching BIM as a collaborative information management process through a continuous improvement assessment lens: a case study
Authors: Nikolic Dragana , Castronovo Fadi , Leicht Robert
Published: June 2021

Purpose

This study explores a pedagogical approach to teaching students a collaborative information delivery process in the context of BIM. The objectives were to understand how students approach this complex, open-ended problem of planning their collaborative process and then identify strategies for improving their process through a plan-do-check-act cycle and reflecting on the applicability of industry standards.

Design/methodology/approach

The authors present a longitudinal case study based on qualitative data from the 3 consecutive years of teaching a senior undergraduate course in a construction engineering program.

Findings

The findings offer a rich picture of how students approached this collaborative process and emphasize the complex nature of teaching BIM as information management process. The authors present instances of how students made sense of BIM standards through applied experience. The findings also demonstrate the value of an outcome-based approach whereby knowledge is gained through an iterative plan-do-check-act cycle. Here, the BEP and model deliverables served only as vehicles to test and apply a range of skills by making them more explicit.

Practical implications

The research contributes to the literature on mechanisms that support students in planning, managing and improving collaborative information strategies in a BIM context. Specifically, the authors illustrate a tension in how to pedagogically deploy industry-oriented process planning methods to establish relevance for students in order to effectively engage in interdisciplinary teams.

Originality/value

In this paper, the authors argue that teaching students how to plan, design and enact effective BIM collaboration information delivery is firmly nested within pedagogical management and communication skills. The authors illustrate with examples how students make sense of BIM approaches by making them concrete and meaningful to their own experience.
Trust mechanisms underlying the self-efficacy-rumour use relationship
Authors: Wang Ping , Hu Yixia , Li Qiao , Yang Hanqin
Published: June 2021

Purpose

Journalism students, a special user group with the dual perspective of both social media general users and online journalists, and their trust in rumours is a valued but understudied topic in relation to preparing rational information users and professionals for rumour control. To reveal these trust mechanisms, this paper aims to identify salient psychological and behavioural factors related to journalism students’ different levels of trust.

Design/methodology/approach

Using structural equation modelling to analyse the survey data of 234 journalism students, this paper tested a theoretical model that considers self-efficacy and the expressive and consumptive use of social media rumours as the antecedents and consequences of trust belief and trust action, respectively.

Findings

Self-efficacy has a positive effect on trust belief but a negative effect on trust action. Trust belief positively affects expressive use of rumours, whereas trust action negatively affects consumptive use.

Practical implications

This study contributes to the cultivation of future online news gatekeepers.

Originality/value

This paper distinguishes journalism students’ trust mechanisms from those of general users and online journalists. The integration of dual process theories provides insights into trust-building processes related to rumours and advances the understanding of the anchoring and adjustment effects of self-efficacy on trust.
The impact of differences in internationalization processes on innovation by emerging economy firms
Authors: Samant Shantala , Thakur-Wernz Pooja , Hatfield Donald E.
Published: June 2021

Purpose

The purpose of this paper is to study the differences in the internationalization process of firms from emerging economies and the impact of their international expansion related choices on the nature of technological innovations developed by these firms. Specifically, the authors compare two principal perspectives on internationalization – the incremental internationalization process (slow, gradually increasing commitments using greenfield investments to similar host countries) and the springboard perspective (aggressive, rapidly increasing commitments using mergers and acquisitions to advanced host countries).

Design/methodology/approach

Building on key differences between the incremental internationalization and springboard perspectives, the authors argue that differences in the speed and mode of entry, as well as the interaction between the mode of entry and location of internationalization, will lead to differences in the types of technologies (mature versus novel) developed by emerging economy firms. The authors examine the hypotheses using panel data from 1997 to 2013 on emerging economy multinationals (EMNEs) from the Indian bio-pharmaceutical industry.

Findings

The findings suggest that firms internationalizing at higher speeds and using cross-border M&As tend to have innovations in mature technologies. The interesting findings can be explained by the challenges faced by emerging economy firms in experiential learning and the assimilation of external knowledge. In addition, the authors find that internationalization to technologically advanced countries weakens the relationship between cross-border M&As and innovation in mature technologies, suggesting that direct learning from technologically advanced environments may help alleviate the assimilation challenges of cross-border M&As.

Originality/value

The authors advance literature on EMNE internationalization by comparing the impact of their choice of internationalization approaches (incremental internationalization or springboard approach) on their innovation performance. The authors contribute to literature on EMNEs that has focused on the determinants of internationalization by identifying the learning implications of internationalization. The authors contribute to the nascent stream of literature on the level of innovation and catching up by EMNEs by performing a fine-grained analysis of the nature of technology innovation.
Quality management of RDP housing construction: myth or reality?
Authors: Amoah Christopher , Van Schalkwyk Tanya , Kajimo-Shakantu Kahilu
Published: June 2021

Purpose

South Africa has a large social housing scheme to provide primary housing for less privileged citizens who obtain an average monthly income of less than R 3,500.00. The government seeks to promote an integrated society by developing sustainable human settlements and quality housing within a subsidy system for different income groups. This study aims to examine whether quality management is applied to the reconstruction and development programme (RDP) housing programme during construction.

Design/methodology/approach

A quantitative survey approach was selected for this study. This involved using a close-ended questionnaire to collect data amongst 1,893 households who are currently residing in government housing units in the city of Bloemfontein, in the Free State province. The questionnaires were self-administered amongst randomly selected respondents based on their availability at the time of the visit to the above area. However, only the occupants of a household were included in the study. The data gathered were analysed by making use of R-programming software.

Findings

The findings revealed that a low level of quality is evident in the already constructed RDP housing units. Most of the inspected units were built with low-quality building materials or were not well-constructed, with derelict structural frames and finishes being evident in most houses. Respondents also indicated that they were not satisfied with the quality of some aspects of the units, such as the plaster and paint finishes, door frames built into walls and uneven floors and floor finishes. These complaints indicate that little to no quality management was applied at the time of construction or even afterwards during the latent defects period.

Research limitations/implications

The survey was limited to responses amongst randomly selected government RDP housing occupants in seven communities in Bloemfontein’s periphery, in the Free State Province of South Africa.

Practical implications

The empirical results from the findings indicate that the South African Government should ensure that quality management is applied during the housing units’ construction. This may mean that a new strategy for verifying the units’ quality will need to be developed, considering the respondents’ concerns by improving the quality of the construction materials and methods used to erect these units. The government should also consider improving contractors’ tender selection criteria to ensure higher quality construction methods, materials and management.

Originality/value

The study has identified quality challenges in constructing the social housing and stated recommendations that will address the identified issues if implemented by the programme implementers. This will help achieve the programme's objective, which is to improve the living conditions of previously disadvantaged individuals through social housing scheme.