bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective immunity induced by CpG ODN‐adjuvanted virus‐like particles containing Toxoplasma gondii proteins
Authors: Kang Hae‐Ji , Chu Ki‐Back , Kim Min‐Ju , Lee Su‐Hwa , Park Hyunwoo , Jin Hui , Moon Eun‐Kyung , Quan Fu‐Shi
Published: October 2020

Aims

To date, a Toxoplasma gondii vaccine for clinical use remains unavailable, though multiple vaccine candidates have been suggested. In our previous studies, unadjuvanted virus‐like particles (VLPs) vaccines expressing multiple T. gondii antigens were confirmed to be protective against T. gondii challenge infection. Yet, the protective efficacy of adjuvanted T. gondii VLP in comparison with the unadjuvanted counterpart requires elucidation.

Methods and Results

In the present study, mice were immunized with the multi‐antigenic VLP vaccines (TG146 VLP) with or without CpG adjuvants and their protective efficacies were compared. CpG‐adjuvanted TG146 VLP vaccine elicited enhanced T gondii‐specific IgG and IgA antibody responses in the sera, mucosal tissue and the brain compared to unadjuvanted VLPs vaccine. Inclusion of CpG adjuvant in vaccines also induced greater CD4+ and CD8+ T‐cell responses, as well as B cell and germinal centre B cell responses from splenocytes and mesenteric lymph nodes. Pro‐inflammatory cytokine response and cyst counts in the brain were drastically diminished in mice immunized with CpG‐adjuvanted VLP vaccines.

Conclusion

Our results demonstrated that CpG‐adjuvanted T. gondii VLPs can significantly enhance the protective efficacy of vaccines against T. gondii infection.
The China Model in Zimbabwe: The Belt and Road Initiative and Beyond
Authors: Ganda Willie D.
Published: October 2020

This article discusses the China model in the context of Zimbabwe's socioeconomic and political trajectory in the past two decades. It shares perspectives on why and how Sino‐Zimbabwe economic relations have failed to produce the desired outcomes. This has been largely influenced by the policy's role as more a political posturing to suit regime interests in the face of international isolation rather than a strategic deployment of the China model. I conclude by giving perspectives on the implications of China's largely self‐interested model of economic engagement with Africa under the new Belt and Road Initiative on the long‐term economic development in Zimbabwe and Africa at large. In the absence of the necessary factors and guiding philosophy, in particular within the public sector management domain, it is highly improbable that the emergence of China as a development partner under the so‐called “Beijing Consensus” will lead to a replication of its success in Zimbabwe and other African countries of the same disposition.

Related Articles (in this Special Issue)

Babones, Salvatore. 2020. “China's Development Model: Can it be Replicated in Sub‐Saharan Africa?” Politics & Policy 48 (5).

Kinyondo, Abel A. 2020. “Does Tanzania's Development Trajectory Borrow from the China Model?” Politics & Policy 48 (5).

Ziso, Edson. 2020. “The Political Economy of the Chinese Model in Ethiopia.” Politics & Policy 48 (5).
Early detection of Neophysopella tropicalis in grapevine leaves and on spore traps by qPCR
Authors: Primiano Isabela V. , Cia Mariana C. , Camargo Luis E. A. , Amorim Lilian
Published: October 2020

Neophysopella tropicalis, one of the causal agents of Asian grapevine leaf rust (AGLR), can cause severe epidemics in Brazil that lead to yield losses in commercial vineyards. An early detection of the pathogen by air sampling of urediniospores on spore traps or in symptomless leaves would be valuable to multiple studies, such as epidemics modelling, risk forecasting, monitoring of pathogen introductions in rust‐free areas, and predicting the beginning of epidemics. This study developed a quantitative PCR (qPCR) protocol to quantify N. tropicalis urediniospores attached to adhesive tapes and in grapevine leaves before symptom appearance. A specific primer pair was designed based on the internal transcribed spacer (ITS) sequence region of the AGLR pathogen. Standard amplification curves using genomic DNA from urediniospores of N. tropicalis and from urediniospores attached to adhesive tapes were established. Grapevine leaves inoculated with N. tropicalis were collected at 2, 5, and 7 days postinoculation (dpi). One primer pair (580F/720R) amplified a 140 bp product in all AGLR isolates but did not amplify products of other rust genera, such as Phakopsora, Puccinia, Hemileia, Tranzschelia, Cerotelium, and Coleosporium. As little as 0.1 pg DNA and 10 urediniospores of N. tropicalis attached to adhesive tapes could be detected. qPCR enabled the detection of the pathogen as early as 2 dpi, before symptom appearance. This method can be used to monitor N. tropicalis inoculum in grapevine‐growing areas and to quantify symptomless infections of the AGLR pathogen.
Differential expression and localization of TRPV channels in the mature sperm of Anas platyrhynchos
Authors: Majhi Rakesh Kumar , Kumar Ashutosh , Giri Sunil C. , Goswami Chandan
Published: October 2020

Sperm cells perform precise chemotactic and thermotactic movement which is crucial for fertilization. However, the key molecules involved in detection of different chemical and physical stimuli which guide the sperm during navigation are not well understood. Ca2+‐signalling mediated by ion channels seem to play important role in motility and other fertility parameters. In this work, we explored the endogenous localization pattern of TRPV channels in the mature spermatozoa of avian species. Using sperm from white pekin duck (Anas platyrhynchos) as the representative avian model, we demonstrate that duck sperm endogenously express the thermosensitive channels TRPV1, TRPV2, TRPV3, TRPV4, and highly Ca2+‐selective channels TRPV5 and TRPV6 in specific yet differential locations. All of these TRPV channels are enriched in the sperm tail, indicating their relevance in sperm motility. Interestingly, the TRPV3 and TRPV4 channels are present in the mitochondrial region. Calcium selective TRPV5 channel is exclusively present in sperm tail and is most abundant among the TRPV channels. This is the first report describing the endogenous presence of TRPV2 and TRPV3 channels in the sperm of any species. Using confocal imaging and super‐resolution imaging, we demonstrate that though the TRPV channels are evolutionarily closely related, they have distinct localization pattern in the duck sperm, which could impact their role in fertilization.
The Good, the Bad, and the Funny: An Ethics of Humor
Authors: Morreall John
Published: October 2020

This article begins by reviewing the overwhelmingly negative assessment of laughter and humor in Western philosophy and in Christianity, arguing that that evaluation arises from a misclassification of amusement as a malicious emotion. It then sketches a play theory of humor in which humor is an activity pursued for pleasure which allows participants to violate linguistic and social norms, especially rules about sincerity. Once we understand humor as a kind of play, familiar ethical objections to jokes based on gender and race are seen to be mistaken, and a new approach to the negative ethics of humor becomes possible. What is more, this play theory also explains how humor is morally praiseworthy in many situations.
Impact of water availability on root growth of sugar beet varieties
Authors: Fitters Tamara F. J. , Mooney Sacha J. , Sparkes Debbie L.
Published: October 2020

On average, sugar beet yield in the UK is reduced by 10% due to water limitation. The root system of a plant is responsible for water uptake and hence an extensive root system is crucial to mitigate drought stress. There might be varietal differences when it comes to plant root system architecture but so far none have been reported in sugar beet. This study shows the results of 2 years of field experiments, examining the rooting patterns and overall plant growth of sugar beet under both rainfed and irrigated conditions. In the first year, three varieties were assessed, and in the second year, five varieties. No significant yield differences were found between the rainfed and irrigated treatments, which is likely due to the applied drought stress only being mild in both years. There were, however, significant varietal differences in plant growth and rooting patterns in rainfed plants which were most distinct when plants were subjected to mild drought stress. Varietal differences observed might indicate the possibility of breeding for certain root traits to mitigate drought stress in sugar beet in the future.
Strategies for forming effective women’s groups
Authors: Santhosh Lekshmi , Harleman Elizabeth , Venado Aida , Farrand Erica , E. Gilbreth Margaret , Keenan Bridget P. , Thompson Vanessa V. , Shah Rupal J.
Published: October 2020

Women are under‐represented at the highest levels of leadership in health care, so many institutions have started forming “women in medicine” affinity groups. In this The Clinical Teacher’s Toolbox, we review the history of women’s professional peer‐to‐peer networking groups in health care, describe the rationale for establishing a women’s group, discuss the goals and common content covered by successful women’s groups, share best practices on forming and sustaining women’s groups, and describe common pitfalls to avoid. When forming a women’s group, identifying the group’s vision, mission, and primary aim statements are important, and early meetings should deliberately establish a tone of inclusion. We acknowledge that the term “women’s groups” implies that gender identity is binary – in reality, these groups are for all who want to combat gender inequities in health care. While early stages of women’s groups typically focus on community‐building, peer networking, and inviting guest speakers to speak about relevant topics, successful groups often ultimately pivot to advocacy, internal capacity‐building, evaluation, and dissemination. To sustain and maintain the group, succession planning, regular opportunities for evaluation, and deliberate planning are essential. Although usual principles of successful small group creation apply, this article outlines unique considerations for how women’s groups can advance gender equity.
Schirmer strip wetting length varies by commercial manufacturer
Authors: Lewin Andrew C. , Liu Chin‐Chi , Yoon Angela , Mironovich Melanie , Miessler Bruna , Carter Renee T.
Published: October 2020

Objective

To determine whether wetting length of Schirmer tear test (STT) strips varies by commercial manufacturer of test.

Animals Studied

Ten normal female beagle cross‐breed dogs.

Procedures

Schirmer tear test strips from four commercial manufacturers were used to assess wetting lengths in‐vitro when exposed to a set volume of water over 1 minute. Digital photography was used to assess the total surface area of Schirmer strips from each manufacturer. Schirmer tear test type 1 was performed on normal dogs over 1 minute with STT strips from the same four commercial manufacturers in a randomized crossover design. ANOVA was used to detect differences between strips from different manufacturers.

Results

Significant differences in wetting length were found between STT strips from different manufacturers in‐vitro (P < .0001) and in‐vivo (P < .0001). STT wetting lengths for the in‐vitro experiments (mean ± SD) were 21.2 ± 0.8 mm (Amcon Laboratories), 27.8 ± 2.7 mm (Merck Animal Health), 30.0 ± 1.7 mm (HUB pharmaceuticals), and 31.5 ± 2.3 mm (Gulden Ophthalmics). STT wetting lengths for the experiments in live dogs (mean ± SD) were 17.5 ± 3.4 mm (Amcon Laboratories), 24.8 ± 3.9 mm (Merck Animal Health), 26.5 ± 3.7 mm (HUB pharmaceuticals), and 24.0 ± 3.9 mm (Gulden Ophthalmics). The surface area of STT strips were found to vary between different manufacturers.

Conclusions

Schirmer tear test type 1 results in dogs are affected by choice of STT strip commercial manufacturer. It is proposed that guidelines are created for the standardization of future STT strip production.
Growth hormone receptor knockout: Relevance to xenotransplantation
Authors: Iwase Hayato , Ball Suyapa , Adams Kent , Eyestone Will , Walters Anneke , Cooper David K. C.
Published: October 2020

Xenotransplantation research has made considerable progress in recent years, largely through the increasing availability of pigs with multiple genetic modifications, effective immunosuppressive therapy, and anti‐inflammatory therapy to protect pig tissues from the primate immune and inflammatory responses and correct molecular incompatibilities. Further study is required regarding identification and investigation of physiological incompatibilities.

Although the exact cause remains uncertain, we and others have observed relatively rapid growth of kidney xenografts after transplantation into nonhuman primates (NHPs). There has also been some evidence of growth, or at least ventricular hypertrophy, of the pig heart after orthotopic transplantation into NHPs. Rapid growth could be problematic, particularly with regard to the heart within the relatively restricted confines of the chest.

It has been suggested that the problem of rapid growth of the pig organ after transplantation could be resolved by growth hormone receptor (GHR) gene knockout in the pig. The GHR, although most well‐known for regulating growth, has many other biological functions, including regulating metabolism and controlling physiological processes. Genetically modified GHRKO pigs have recently become available. We provide data on their growth compared to comparable pigs that do not include GHRKO, and we have reviewed the literature regarding the effect of GHRKO, and its relevance to xenotransplantation.
A Decade Later: The Impact of Empowerment on Women in Sitio Alitaptap, Province of Nueva Ecija, Philippines and Its Effect on Peace and Social Order
Authors: Bustamante Jacinto Yango
Published: October 2020

This study examined the impact of empowerment on women after a decade of its rigid campaign in the province of Nueva Ecija, Philippines and its effect on peace and social order as perceived by the residents of sitio Alitaptap, Nueva Ecija. The researcher utilized a descriptive research design using a self-devised questionnaire to gather information. The findings revealed that the respondents have a high level of conformity to the actions of local government unit to empower women. As to the impact of empowerment on women, the respondents agreed to the positive result of the action taken by the local government unit. The study showed that empowering women brought peace and social order and the quality of program implementation in the place caused high degree of effectiveness in the performance of duty of local officials. However, there are some things that are not clear to the respondents as there are some questions where respondents stand neutral. The study revealed that not only will women gain knowledge of their rights on the action of the local government but will also teach men how to respect women. The only negative result of the study is the threat that women may use their rights to prejudice men that may result in social disorder.
Counter-Propagating Rotating Stall of Vaned Diffuser in a Centrifugal Compressor Near Design Condition
Authors: Du Yu , Dou Hua-Shu , Lu Fuan
Published: October 2020

Unstable flow in the vaned diffuser of a centrifugal compressor stage near design condition is investigated by numerical simulation. The simulation is performed with the unsteady Navier–Stokes equations and three different turbulence models. Comparisons of the characteristic curves of the stage have been carried out between simulation and experiment, and good agreement is obtained. The fluctuation signals near the interface between the impeller and the diffuser are also quantitatively analyzed from macro and micro scales under a series of mass flow conditions. The simulation results show that an abnormal counter-propagating rotating stall in the vaned diffuser is detected near design condition. The rotating stall displays that four stall cells near the shroud side of the vaned diffuser propagate slowly at a rate of approximately 0.675% of the impeller rotating frequency along the opposite direction of the impeller rotation. The propagation speed increases as the mass flow decreases. The generation and propagation mechanisms of this phenomenon are elucidated, respectively. It is found that flow separation near the diffuser shroud side is produced due to the spanwise variation of flow angles near the impeller exit, which leads to the generation of stall cells in the diffuser. The circumferential propagation of the rotating stall cells is propelled by the accumulation and release of the fluid energy from impeller passages. Further studies show that this phenomenon can be restrained by modifying the installation angle of diffuser vanes.
Buoyancy Control Device Enabled by Reversible Proton Exchange Membrane Fuel Cells for Fine Depth Control
Authors: Yazji Jalal , Keow Alicia Li Jen , Zaidi Hamza , Torres Luke T. , Leroy Christopher , Chen Zheng
Published: October 2020

Fine buoyancy control is essential for underwater robots to maintain neutral buoyancy despite dynamic changes in environmental conditions. This paper introduces a novel buoyancy control system that uses reversible fuel cells (RFC) as a mass-to-volume engine to change the underwater robots' buoyancy. The RFC uses both the water electrolysis process and fuel cell reaction to produce and consume gases in a flexible bladder for volume change. Unlike conventional actuators such as motors and pistons used in buoyancy control, this mechanism is silent, compact, and energy-efficient. A dynamic model that described the dynamics of the RFC-enabled buoyancy change is presented. Then, a proportional-derivative (PD) controller is designed to position the device at any depth underwater. A prototype device is built to validate the dynamic model and the performance of the feedback controller. Experimental results demonstrate a fine depth control performance with 4 cm accuracy and 90 s settling time. The compact buoyancy design is readily integrable with small underwater robots for fine depth change allowing the robots to save actuation energy.
Interlimb Neuromuscular Responses During Fatiguing, Bilateral, Leg Extension Exercise at a Moderate Versus High Load
Authors: Dinyer Taylor K. , Succi Pasquale J. , Byrd M. Travis , Voskuil Caleb C. , Soucie Evangeline P. , Bergstrom Haley C.
Published: October 2020

This study determined the load- and limb-dependent neuromuscular responses to fatiguing, bilateral, leg extension exercise performed at a moderate (50% one-repetition maximum [1RM]) and high load (80% 1RM). Twelve subjects completed 1RM testing for the bilateral leg extension, followed by repetitions to failure at 50% and 80% 1RM, on separate days. During all visits, the electromyographic (EMG) and mechanomyographic (MMG), amplitude (AMP) and mean power frequency (MPF) signals were recorded from the vastus lateralis of both limbs. There were no limb-dependent responses for any of the neuromuscular signals and no load-dependent responses for EMG AMP, MMG AMP, or MMG MPF (p = .301–.757), but there were main effects for time that indicated increases in EMG and MMG AMP and decreases in MMG MPF. There was a load-dependent decrease in EMG MPF over time (p = .032) that suggested variability in the mechanism responsible for metabolite accumulation at moderate versus high loads. These findings suggested that common drive from the central nervous system was used to modulate force during bilateral leg extension performed at moderate and high loads.
An extremely metal-deficient globular cluster in the Andromeda Galaxy
Authors: Larsen Søren S. , Romanowsky Aaron J. , Brodie Jean P. , Wasserman Asher
Published: October 2020

A relic star cluster under the floor

Globular clusters (GCs) are gravitationally bound assemblies of thousands to millions of stars that orbit in the outskirts of large galaxies. GCs consist of old stars with low metallicity containing low proportions of chemical elements heavier than hydrogen and helium. However, GCs appear to have a minimum metallicity, known as the floor, implying that at least some of those elements were required for their formation. Larsen
et al.
have found a GC in the nearby Andromeda Galaxy with a metallicity beneath the floor. This unexpected discovery will inform models of GC formation and incorporation into galaxies.

Science
, this issue p.
970
Flawed research and its enduring repercussions
The Doctor Who Fooled the World
Brian Deer
Johns Hopkins University Press, 2020. 408 pp.
Authors: Offit Paul A.
Published: October 2020

A journalist recounts how he exposed problems with a study linking vaccines and autism
The mouse
Sry
locus harbors a cryptic exon that is essential for male sex determination
Authors: Miyawaki Shingo , Kuroki Shunsuke , Maeda Ryo , Okashita Naoki , Koopman Peter , Tachibana Makoto
Published: October 2020

Two rather than one

For several decades, it has been believed that the mammalian sex-determining gene
Sry
contains a single exon. Miyawaki
et al.
have now identified a cryptic second exon of mouse
Sry
. Loss- and gain-of-function analyses revealed that the two-exon SRY (SRY-T), not the canonical single exon–encoded SRY (SRY-S), is the bona fide testis-determining factor.
Sry
exon2 is composed of retrotransposon-derived sequences. The SRY-S carboxyl terminus contains a degradation sequence (degron), whereas the SRY-T carboxyl terminus encoded in the
Sry
exon2 is degron free, thereby conferring protein stability on SRY-T.

Science
, this issue p.
121
Beyond aggregation: Pathological phase transitions in neurodegenerative disease
Authors: Mathieu Cécile , Pappu Rohit V. , Taylor J. Paul
Published: October 2020

Over the past decade, phase transitions have emerged as a fundamental mechanism of cellular organization. In parallel, a wealth of evidence has accrued indicating that aberrations in phase transitions are early events in the pathogenesis of several neurodegenerative diseases. We review the key evidence of defects at multiple levels, from phase transition of individual proteins to the dynamic behavior of complex, multicomponent condensates in neurodegeneration. We also highlight two concepts, dynamical arrest and heterotypic buffering, that are key to understanding how pathological phase transitions relate to pleiotropic defects in cellular functions and the accrual of proteinaceous deposits at end-stage disease. These insights not only illuminate disease etiology but also are likely to guide the development of therapeutic interventions to restore homeostasis.
Translating genetic risk of Alzheimer’s disease into mechanistic insight and drug targets
Authors: Sierksma Annerieke , Escott-Price Valentina , De Strooper Bart
Published: October 2020

To provide better prevention and treatment, we need to understand the environmental and genetic risks of Alzheimer’s disease (AD). However, the definition of AD has been confounded with dementia in many studies. Thus, overinterpretation of genetic findings with regard to mechanisms and drug targets may explain, in part, controversies in the field. Here, we analyze the different forms of genetic risk of AD and how these can be used to model disease. We stress the importance of studying gene variants in the right cell types and in the right pathological context. The lack of mechanistic understanding of genetic variation has become the major bottleneck in the search for new drug targets for AD.
Shifts and drifts in prion science
Authors: Aguzzi Adriano , De Cecco Elena
Published: October 2020

Important questions remain unanswered since prions were discovered four decades ago
A latent lineage potential in resident neural stem cells enables spinal cord repair
Authors: Llorens-Bobadilla Enric , Chell James M. , Le Merre Pierre , Wu Yicheng , Zamboni Margherita , Bergenstråhle Joseph , Stenudd Moa , Sopova Elena , Lundeberg Joakim , Shupliakov Oleg , Carlén Marie , Frisén Jonas
Published: October 2020

Spinal cord stem cells

Injuries to the mammalian spinal cord do not heal easily. Llorens- Bobadilla
et al.
studied mouse ependymal cells, which function as stem cells for the spinal cord (see the Perspective by Becker and Becker). Chromatin accessibility and transcriptomic assays revealed that these cells carry a latent ability to differentiate into oligodendrocytes, which is much needed for remyelination of axons around an injury. The ependymal cells were triggered to differentiate into oligodendrocytes by expression of the oligodendrocyte lineage transcription factor OLIG2. Expression of OLIG2 in ependymal cells specifically and inducibly enabled the production of oligodendrocytes. The ependymal-derived oligodendrocytes aided axon remyelination and improved axon conduction after spinal cord injury.

Science
, this issue p.
eabb8795
; see also p.
36
Vapor-assisted deposition of highly efficient, stable black-phase FAPbI
3
perovskite solar cells
Authors: Lu Haizhou , Liu Yuhang , Ahlawat Paramvir , Mishra Aditya , Tress Wolfgang R. , Eickemeyer Felix T. , Yang Yingguo , Fu Fan , Wang Zaiwei , Avalos Claudia E. , Carlsen Brian I. , Agarwalla Anand , Zhang Xin , Li Xiaoguo , Zhan Yiqiang , Zakeeruddin Shaik M. , Emsley Lyndon , Rothlisberger Ursula , Zheng Lirong , Hagfeldt Anders , Grätzel Michael
Published: October 2020

Moving a perovskite into the black

The bandgap of the black α-phase FAPbI
3
(where FA is formamidinium) is nearly ideal for solar cells, but it is unstable with respect to the photoinactive yellow δ-phase. Lu
et al.
found that a film of the yellow phase was converted to a highly crystalline black phase by vapor exposure to methylammonium thiocyanate at 100°C, and it retained this structure after 500 hours at 85°C. Solar cells fabricated with this material had a power conversion efficiency of more than 23%. After 500 hours under maximum power tracking and a period of dark recovery, 94% of the original efficiency was retained.

Science
, this issue p.
eabb8985
A universal system for digitization and automatic execution of the chemical synthesis literature
Authors: Mehr S. Hessam M. , Craven Matthew , Leonov Artem I. , Keenan Graham , Cronin Leroy
Published: October 2020

Paper in, product out

A typical chemist running a known reaction will start by finding the method described in a published paper. Mehr
et al.
report a software platform that uses natural language processing to translate the organic chemistry literature directly into editable code, which in turn can be compiled to drive automated synthesis of the compound in the laboratory. The synthesis procedure is intended to be universally applicable to robotic systems operating in a batch reaction architecture. The full process is demonstrated for synthesis of an analgesic as well as common oxidizing and fluorinating agents.

Science
, this issue p.
101
Training tomorrow's scientists
Equity in Science
Julie R. Posselt
Stanford University Press, 2020. 240 pp.
Authors: Huderson Ashley
Published: October 2020

Prioritizing STEM diversity, equity, and inclusion requires rethinking graduate education
Multicenter Performance Evaluation of the Simplexa Bordetella Direct Kit in Nasopharyngeal Swab Specimens
Authors: Chow Siu-Kei , Arbefeville Sophie , Boyanton Bobby L. , Dault Emily M. , Dunn James , Ferrieri Patricia , Greene Wallace , Pence Morgan A. , Otiso Joshua , Richter Sandra , Schutzbank Ted E.
Published: October 2020

Detection ofBordetella pertussisandBordetella parapertussisusing molecular methods is sensitive and specific with a short turnaround time compared to other diagnostic methods. In this multicenter study, we compared the performance of the Simplexa Bordetella Direct kit to those of other molecular assays in detecting and differentiatingB. pertussisandB. parapertussisin nasopharyngeal swab specimens. The limits of detection (LODs) were 150 CFU/ml or 3 fg/μl of DNA forB. pertussisand 1,500 CFU/ml or 10 fg/μl of DNA forB. parapertussis.
Positive Impact of Routine Testing for Enterovirus and Parechovirus on Length of Hospitalization and Antimicrobial Use among Inpatients ≤6 Months of Age
Authors: Lee Brian R. , Sasidharan Anjana , Harrison Chris J. , Selvarangan Rangaraj
Published: October 2020

Enterovirus (EV) and parechovirus (PeV) are leading viral causes of central nervous system (CNS) infection among hospitalized neonates and young infants, yet testing for PeV is not routinely performed. The goal of our study was to determine how EV and PeV CSF RT-PCR testing impacted the duration of antibiotic use and the length of hospitalization (LOS) in children ≤6 months old with suspected CNS infection. This retrospective cohort study at Children’s Mercy Kansas City evaluated data from patients ≤6 months old for whom routine CSF EV and PeV reverse transcription-PCR (RT-PCR) testing was performed during January 2011 to December 2018.
Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index: a Rapid and Accessible Tool That Exploits Genomic Data in Public Health and Clinical Microbiology Applications
Authors: Rodrigues Charlene M. C. , Jolley Keith A. , Smith Andrew , Cameron J. Claire , Feavers Ian M. , Maiden Martin C. J.
Published: October 2020

As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole-genome sequence data by nonspecialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD) since their licensure in 2013 and 2014. These vaccines have different components and different levels of coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate, including (i) the presence of particular vaccine antigen variants, (ii) the expression of vaccine antigens, and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing.
A Novel Mechanism Underlying Antiviral Activity of an Influenza Virus M2-Specific Antibody
Authors: Manzoor Rashid , Eguchi Nao , Yoshida Reiko , Ozaki Hiroichi , Kondoh Tatsunari , Okuya Kosuke , Miyamoto Hiroko , Takada Ayato
Published: October 2020

Although the IAV HA is the major target of neutralizing antibodies, most of the antibodies are HA subtype specific, restricting the potential of HA-based vaccines. On the contrary, the IAV M2 protein has been studied as a vaccine antigen to confer cross-protective immunity against IAVs with multiple HA subtypes, since M2 is antigenically conserved. Although a number of studies highlight the protective role of anti-HA neutralizing and nonneutralizing antibodies, precise information on the molecular mechanism of action of M2-specific antibodies is still obscure. In this study, we found that an anti-M2 antibody interfered with the HA-M2 association, which is important for efficient budding of progeny virus particles from infected cells. The antiviral activity was IAV strain dependent despite the similar binding capacity of the antibody to M2, and, interestingly, HA was involved in susceptibility to the antibody. Our data provide a novel mechanism underlying antiviral activity of M2-specific antibodies.
Evaluating the Shinumo-Sespe drainage connection: Arguments against the “old” (70–17 Ma) Grand Canyon models for Colorado Plateau drainage evolution
Authors: Karlstrom Karl E. , Jacobson Carl E. , Sundell Kurt E. , Eyster Athena , Blakey Ron , Ingersoll Raymond V. , Mulder Jacob A. , Young Richard A. , Beard L. Sue , Holland Mark E. , Shuster David L. , Winn Carmen , Crossey Laura
Published: October 2020

The provocative hypothesis that the Shinumo Sandstone in the depths of Grand Canyon was the source for clasts of orthoquartzite in conglomerate of the Sespe Formation of coastal California, if verified, would indicate that a major river system flowed southwest from the Colorado Plateau to the Pacific Ocean prior to opening of the Gulf of California, and would imply that Grand Canyon had been carved to within a few hundred meters of its modern depth at the time of this drainage connection. The proposed Eocene Shinumo-Sespe connection, however, is not supported by detrital zircon nor paleomagnetic-inclination data and is refuted by thermochronology that shows that the Shinumo Sandstone of eastern Grand Canyon was >60 °C (∼1.8 km deep) and hence not incised at this time. A proposed 20 Ma (Miocene) Shinumo-Sespe drainage connection based on clasts in the Sespe Formation is also refuted. We point out numerous caveats and non-unique interpretations of paleomagnetic data from clasts. Further, our detrital zircon analysis requires diverse sources for Sespe clasts, with better statistical matches for the four “most-Shinumo-like” Sespe clasts with quartzites of the Big Bear Group and Ontario Ridge metasedimentary succession of the Transverse Ranges, Horse Thief Springs Formation from Death Valley, and Troy Quartzite of central Arizona. Diverse thermochronologic and geologic data also refute a Miocene river pathway through western Grand Canyon and Grand Wash trough. Thus, Sespe clasts do not require a drainage connection from Grand Canyon or the Colorado Plateau and provide no constraints for the history of carving of Grand Canyon. Instead, abundant evidence refutes the “old” (70–17 Ma) Grand Canyon models and supports a <6 Ma Grand Canyon.
Possible affective cognitive cerebellar syndrome in a young patient with COVID-19 CNS vasculopathy and stroke
Authors: Chia Kai Xin , Polakhare Sonali , Bruno Stefania Dafne
Published: October 2020

Early case series suggest that about one-third of patients with COVID-19 present with neurological manifestations, including cerebrovascular disease, reported in 2%–6% of hospitalised patients. These are generally older patients with severe infection and comorbidities. Here we discuss the case of a previously fit and well 39-year-old man who presented with fever and respiratory symptoms, evolving in pneumonia with hypoxia but only requiring continuous positive airway pressure. After resolution of the respiratory disease, the patient developed focal neurology and was found to have bilateral occipital, thalamic and cerebellar infarcts. A diagnosis of COVID-19 central nervous system vasculopathy was made. He developed a florid neuropsychiatric syndrome, including paranoia, irritability, aggression and disinhibition, requiring treatment with antipsychotics and transfer to neurorehabilitation. Neuropsychometry revealed a wide range of cognitive deficits. The rapid evolution of the illness was matched by fast resolution of the neuropsychiatric picture with mild residual cognitive impairment.
Effectiveness of pelvic floor muscle training with and without electromyographic biofeedback for urinary incontinence in women: multicentre randomised controlled trial
Authors: Hagen Suzanne , Elders Andrew , Stratton Susan , Sergenson Nicole , Bugge Carol , Dean Sarah , Hay-Smith Jean , Kilonzo Mary , Dimitrova Maria , Abdel-Fattah Mohamed , Agur Wael , Booth Jo , Glazener Cathryn , Guerrero Karen , McDonald Alison , Norrie John , Williams Louise R , McClurg Doreen
Published: October 2020

Objective

To assess the effectiveness of pelvic floor muscle training (PFMT) plus electromyographic biofeedback or PFMT alone for stress or mixed urinary incontinence in women.

Design

Parallel group randomised controlled trial.

Setting

23 community and secondary care centres providing continence care in Scotland and England.

Participants

600 women aged 18 and older, newly presenting with stress or mixed urinary incontinence between February 2014 and July 2016: 300 were randomised to PFMT plus electromyographic biofeedback and 300 to PFMT alone.

Interventions

Participants in both groups were offered six appointments with a continence therapist over 16 weeks. Participants in the biofeedback PFMT group received supervised PFMT and a home PFMT programme, incorporating electromyographic biofeedback during clinic appointments and at home. The PFMT group received supervised PFMT and a home PFMT programme. PFMT programmes were progressed over the appointments.

Main outcome measures

The primary outcome was self-reported severity of urinary incontinence (International Consultation on Incontinence Questionnaire-urinary incontinence short form (ICIQ-UI SF), range 0 to 21, higher scores indicating greater severity) at 24 months. Secondary outcomes were cure or improvement, other pelvic floor symptoms, condition specific quality of life, women’s perception of improvement, pelvic floor muscle function, uptake of other urinary incontinence treatment, PFMT self-efficacy, adherence, intervention costs, and quality adjusted life years.

Results

Mean ICIQ-UI SF scores at 24 months were 8.2 (SD 5.1, n=225) in the biofeedback PFMT group and 8.5 (SD 4.9, n=235) in the PFMT group (mean difference −0.09, 95% confidence interval −0.92 to 0.75, P=0.84). Biofeedback PFMT had similar costs (mean difference £121 ($154; €133), −£409 to £651, P=0.64) and quality adjusted life years (−0.04, −0.12 to 0.04, P=0.28) to PFMT. 48 participants reported an adverse event: for 23 this was related or possibly related to the interventions.

Conclusions

At 24 months no evidence was found of any important difference in severity of urinary incontinence between PFMT plus electromyographic biofeedback and PFMT alone groups. Routine use of electromyographic biofeedback with PFMT should not be recommended. Other ways of maximising the effects of PFMT should be investigated.

Trial registration

ISRCTN57756448.
From words to actions: systematic review of interventions to promote sexual and reproductive health of persons with disabilities in low- and middle-income countries
Authors: Hameed Shaffa , Maddams Alexander , Lowe Hattie , Davies Lowri , Khosla Rajat , Shakespeare Tom
Published: October 2020

Introduction

Persons with disabilities have the same sexual and reproductive health and rights (SRHR) as non-disabled persons. Yet they face numerous barriers in their access to sexual and reproductive health services and their rights are often not met. Evidence on SRHR for persons with disabilities is sparse, particularly evaluations of interventions demonstrating ‘what works.’ This systematic review assessed interventions to promote SRHR for persons with disabilities in low- and middle-income countries.

Methods

We searched for qualitative, quantitative or mixed method observational studies representing primary research, published between 2010 and 2019, using MEDLINE, Embase, PubMed, Global Health and CINAHL Plus. Search strings were compiled for different elements of SRHR and for all forms of disability. 24,919 records were screened, leading to over 380 relevant papers, most of which were descriptive, focussing on needs and barriers to SRHR needs being fulfilled. Of the 33 full-text articles assessed for eligibility, 18 were included in the synthesis. All included studies were assessed for bias and quality of evidence, using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and RATS (relevance, appropriateness, transparency andsoundness) tools. Among the 16 interventions (from 18 articles), 25% had low risk of bias, 31% had moderate risk of bias and 44% had high risk of bias. Data analysis used narrative synthesis; a method suited for systematic reviews with heterogeneous studies. We used Levesque healthcare access model to analyse the focus of interventions.

Results

11 interventions were from upper middle-income settings; two from lower-income settings; only one operated in rural areas. Interventions addressed intellectual impairment (6), visual impairment (6), hearing impairment (4), mental health conditions (2) and physical impairments (2). Most interventions (15/16) focus on information provision and awareness raising. We could not identify any intervention promoting access to maternal health, family planning and contraception, or safe abortion for people with disabilities.

Conclusion

This systematic review has highlighted stark gaps in evidence. More rigorous evaluations are needed.
Cost-effectiveness of internet-based vestibular rehabilitation with and without physiotherapy support for adults aged 50 and older with a chronic vestibular syndrome in general practice
Authors: van Vugt Vincent A , Bosmans Judith E , Finch Aureliano P , van der Wouden Johannes C , van der Horst Henriëtte E , Maarsingh Otto R
Published: October 2020

Objectives

To evaluate the cost-effectiveness of stand-alone and blended internet-based vestibular rehabilitation (VR) in comparison with usual care (UC) for chronic vestibular syndromes in general practice.

Design

Economic evaluation alongside a three-armed, individually randomised controlled trial.

Setting

59 Dutch general practices.

Participants

322 adults, aged 50 years and older with a chronic vestibular syndrome.

Interventions

Stand-alone VR consisted of a 6-week, internet-based intervention with weekly online sessions and daily exercises. In blended VR, this intervention was supplemented with face-to-face physiotherapy support. UC group participants received usual general practice care without restrictions.

Main outcome measures

Societal costs, quality-adjusted life years (QALYs), Vertigo Symptom Scale—Short Form (VSS-SF), clinically relevant response (≥3 points VSS-SF improvement).

Results

Mean societal costs in both the stand-alone and blended VR groups were statistically non-significantly higher than in the UC group (mean difference (MD) €504, 95% CI −1082 to 2268; and €916, 95% CI −663 to 2596). Both stand-alone and blended VR groups reported non-significantly more QALYs than the UC group (MD 0.02, 95% CI −0.00 to 0.04; and 0.01, 95% CI −0.01 to 0.03), and significantly better VSS-SF Scores (MD 3.8 points, 95% CI 1.7 to 6.0; and 3.3 points, 95% CI 1.3 to 5.2). For stand-alone VR compared with UC, the probability of cost-effectiveness was 0.95 at a willingness-to-pay ratio of €24 161/QALY, €600/point improvement in VSS-SF and €8000/clinically relevant responder in VSS-SF. For blended VR versus UC, the probability of cost-effectiveness was 0.95 at a willingness-to-pay ratio of €123 335/QALY, €900/point improvement in VSS-SF and €24 000/clinically relevant responder in VSS-SF.

Conclusion

Stand-alone and blended internet-based VR non-significantly increased QALYs and significantly reduced vestibular symptoms compared with UC, while costs in both groups were non-significantly higher. Stand-alone VR has the highest probability to be cost-effective compared with UC.

Trial registration number

The Netherlands Trial Register NTR5712.
Publication bias in pediatric emergence delirium: a cross-sectional analysis of ClinicalTrials.gov and ClinicalTrialsRegister.eu
Authors: Meyburg Jochen , Ries Markus
Published: October 2020

Objectives

Emergence delirium (ED) is a frequent and potentially serious complication of general anaesthesia in children. Although there are various treatment strategies, no general management recommendations can be made. Selective reporting of study results may impair clinical decision-making. We, therefore, analysed whether the results of completed registered clinical studies in patients with paediatric ED are publicly available or remain unpublished.

Design

Cross-sectional analysis.

Setting

ClinicalTrials.gov and ClinicalTrialsRegister.eu.

Participants and outcome measures

We determined the proportion of published and unpublished studies registered at ClinicalTrials.gov and ClinicalTrialsRegister.eu that were marked as completed by 1st September 2018. The major trial and literature databases were used to search for publications. In addition, the study investigators were contacted directly. For published trials, time to publication was calculated as the difference in months between study completion date and publication date.

Results

Of the 44 registered studies on paediatric ED, only 24 (54%) were published by September 2019. Published trials contained data from n=2556 patients, whereas n=1644 patients were enrolled in unpublished trials. Median time to publication was 19 months. Studies completed in recent years were published faster, but still only 9 of 24 trials were published within 12 months of completion.

Conclusion

There is a distinct publication gap in clinical research in paediatric ED that may have an impact on meta-analyses and clinical practice.
Ghost ileostomy versus conventional loop ileostomy in patients undergoing low anterior resection for rectal cancer (DRKS00013997): protocol for a randomised controlled trial
Authors: Hüttner Felix J , Probst Pascal , Mihaljevic André , Contin Pietro , Dörr-Harim Colette , Ulrich Alexis , Schneider Martin , Büchler Markus W , Diener Markus K , Knebel Phillip
Published: October 2020

Introduction

Anastomotic leakage is the most important complication in colorectal surgery occurring in up to 20% after low anterior rectal resection. Therefore, a diverting ileostomy is usually created during low anterior resection to protect the anastomosis or rather to diminish the consequences in case of anastomotic leakage. The so-called virtual or ghost ileostomy is a pre-stage ostomy that can be easily exteriorised, if anastomotic leakage is suspected, in order to avoid the severe consequences of anastomotic leakage. On the other hand, an actual ileostomy can be avoided in patients, who do not develop anastomotic leakage.

Methods and analysis

The GHOST trial is a randomised controlled pilot trial comparing ghost ileostomy with conventional loop ileostomy in patients undergoing low anterior resection with total mesorectal excision for rectal cancer. After screening for eligibility and obtaining informed consent, a total of 60 adult patients are included in the trial. Patients are intraoperatively randomised to the trial groups in a 1:1 ratio after assuring that none of the intraoperative exclusion criteria are present. The main outcome parameter is the comprehensive complication index as a measure of safety. Further outcomes include specific complications, stoma-related complications, complications of ileostomy closure, frequency of transformation of ghost ileostomy into conventional ileostomy, frequency of terminal ostomy creation, proportion of patients with an ostomy at 6 months after index surgery, anorectal function (Wexner score) and quality of life assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Follow-up for each individual patient will be 6 months.

Ethics and dissemination

The GHOST trial has been approved by the Medical Ethics Committee of Heidelberg University (reference number S-694/2017). If the intervention proves to be safe, loop ileostomy could be spared in a large proportion of patients, thus also avoiding stoma-related complications and a second operation (ileostomy closure) with its inherent complications in these patients.

Trial registration number

German Clinical Trials Registry (DRKS00013997); Universal Trial Number: U1111-1208-9742.