bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Outcomes of Wise-Pattern, Two-Stage Breast Reduction-Reconstruction with and without Acellular Dermal Matrix
Authors: Patel Ashraf A. , Kayaleh Hana , Sala Luke A. , Peterson Dylan J. , Upadhyaya Prashant K.
Published: August 2021

Background:

Aesthetic results in breast reconstruction for ptotic/obese breasts may be improved when using Wise-pattern closures compared with nipple-sparing mastectomies. In two-stage reconstruction, acellular dermal matrix is commonly used to support the prosthesis. This study tests the efficacy of an alternate technique that uses deepithelialized excess breast skin in lieu of acellular dermal matrix. To better understand whether acellular dermal matrix is necessary, the authors compared postoperative outcomes from reduction-reconstructions that used matrix to those that did not.

Methods:

The authors retrospectively reviewed the outcomes of patients who underwent staged breast reconstruction following Wise-pattern closures between September of 2016 and October of 2019. Two cohorts were created based on whether acellular dermal matrix was used. Charts were reviewed for incidence of postoperative complications.

Results:

A total of 164 breasts were reconstructed in 85 female patients. The acellular dermal matrix cohort consisted of 68 breasts, whereas the non–acellular dermal matrix cohort included 96 breasts. After the first stage, the incidence of one or more complications was similar between cohorts (acellular dermal matrix, 32.4 percent; nonmatrix, 35.4 percent; p = 0.684). Minor infection rates were significantly higher in reconstructions using acellular dermal matrix (16.2 percent versus 6.3 percent; p = 0.040). After the second stage, the complication incidence was also similar between cohorts (acellular dermal matrix, 16.2 percent; nonmatrix, 13.5 percent; p = 0.638). Final follow-up time was 445.2 days.

Conclusions:

Overall complication rates following both stages of reconstruction were similar with and without acellular dermal matrix. When acellular dermal matrix was used, minor infection rates were higher following expander placement. In patients desiring a reduction-reconstruction, the authors find the deepithelialized dermal flap provides ample prosthesis support, without the need for acellular dermal matrix. 

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Neurotization Preferences in Smile Reanimation: A Discrete Choice Experiment
Authors: Dusseldorp Joseph R. , Naunheim Matthew R. , Quatela Olivia , Fortier Emily , Hadlock Tessa A. , Jowett Nate
Published: August 2021

Background:

Common donor nerve options in smile reanimation include ipsilateral trigeminal motor or contralateral facial nerve branches. Neurotization preference may be influenced by multiple factors, whose relative importance remains poorly understood. In this article, decision-making in smile reanimation is assessed using a stated preference model.

Methods:

Qualitative interviews with facial palsy patients identified five relevant attributes for study: smile type (“smile when biting” versus “smile spontaneously” as proxies for trigeminal versus cross-facial neurotization), number of operations, success rates, complication rates, and side effects. Community volunteers (n = 250) completed a discrete-choice experiment relevant to free muscle transfer for smile reanimation. Preoperative and postoperative states were demonstrated through video vignettes, together with explanation of surgical risks, consequences, and benefits. Attribute importance was modeled using hierarchical Bayes estimation.

Results:

Two hundred forty-one responses met quality controls. Attribute importance ranked as follows: chance of success, 37.3 percent; smile type, 21.4 percent; side effects, 13.9 percent; complication rates, 13.8; and number of operations, 13.6 percent. All attributes significantly correlated with decision making (p < 0.0001). An aggregate response model revealed most participants (67.6 percent; standard error, 3.0 percent) preferred smile reanimation by cross-facial (assuming a success rate of 80 percent) as opposed to ipsilateral trigeminal motor branch neurotization. When the success rate for cross-facial neurotization was reduced below 67 percent, trigeminal neurotization was preferred.

Conclusions:

Despite a higher risk of failure, most respondents preferred a cross-facial as opposed to trigeminal neurotization strategy for smile reanimation. These findings highlight the complexity of decision-making and need for individualized risk tolerance assessment in the field of facial reanimation.
Resident Selection: The Role of Assessment of Emotional Intelligence and Grit
Authors: Luce Edward A.
Published: August 2021

The ability of our resident selection process to identify individuals who will ultimately become competent plastic surgeons is crucial to the specialty’s future. Current criteria in use are not productive of that outcome. The presence of emotional intelligence and the element of grit have been incorporated in business and the military as factors to be evaluated in potential candidates. Plastic surgery should initiate an investigation of inclusion of a similar assessment of resident applicants.
Severe acute respiratory syndrome coronavirus-2 antibody prevalence in people with and without HIV in rural Western Kenya, January to March 2020
Authors: Crowell Trevor A. , Daud Ibrahim I. , Maswai Jonah , Owuoth John , Sing’oei Valentine , Imbach Michelle , Dear Nicole , Sawe Fred , Eller Leigh Anne , Polyak Christina S. , Ake Julie A.
Published: August 2021

Among 582 participants in Western Kenya who were retrospectively tested from January through March 2020, 19 (3.3%) had detectable SARS-CoV-2 antibodies. The prevalence of detectable SARS-CoV-2 antibodies was similar between participants with and without HIV (3.1% vs. 4%, P = 0.68). One participant reported a cough in the preceding week but others denied symptoms. These may represent cross-reactivity or asymptomatic infections that predated the first reported COVID-19 cases in Kenya.
Sexually transmitted infections and depot medroxyprogesterone acetate do not impact protection from simian HIV acquisition by long-acting cabotegravir in macaques
Authors: Vishwanathan Sundaram Ajay , Zhao Chunxia , Luthra Roopa , Khalil George K. , Morris Monica M. , Dinh Chuong , Gary Michelle J. , Mitchell James , Spreen William R. , Pereira Lara E. , Heneine Walid , García-Lerma J. Gerardo , McNicholl Janet M.
Published: August 2021

Objective:

We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection. Here, we reassessed CAB-LA efficacy in the presence of depot medroxyprogesterone acetate and multiple sexually transmitted infections (STIs) that are known to increase HIV susceptibility in women.

Design:

Two macaque models of increasing vaginal STI severity were used for efficacy assessment.

Methods:

The first study (n = 11) used a double STI model that had repeated exposures to two vaginal STI, Chlamydia trachomatis and Trichomonas vaginalis. Six animals were CAB-LA treated and five were controls. The second study (n = 9) included a triple STI model with repeated exposures to C. trachomatis, T. vaginalis and syphilis, and the contraceptive, depot medroxyprogesterone acetate (DMPA). Six animals were CAB-LA treated and three were controls. All animals received up to 14 vaginal SHIV challenges. A survival analysis was performed to compare the number of SHIV challenges to infection in the drug-treated group compared with untreated controls over time.

Results:

All six CAB-LA treated animals in both models, the double STI or the triple STI-DMPA model, remained protected after 14 SHIV vaginal challenges, while the untreated animals became SHIV-infected after a median of two challenges (log-rank P < 0.001) or one challenge (log-rank P = 0.002), respectively. Both models recapitulated human STI disease, with vaginal discharge, ulcers, and seroconversion.

Conclusion:

In these high and sustained susceptibility models spanning more than 3 months, CAB-LA maintained complete efficacy, demonstrating robustness of the CAB-LA dose used in clinical trials, and suggesting its insensitivity to multiple STIs and DMPA.
Asymmetric cross-strain protection for amphibians exposed to a fungal-metabolite prophylactic treatment
Authors: Barnett K. M. , Detmering S. E. , McMahon T. A. , Civitello D. J.
Published: August 2021

Chytridiomycosis, an infectious disease of amphibians caused by the fungal pathogen
Batrachochytrium dendrobatidis
(Bd), poses an imminent conservation threat. The global spread of Bd has led to mass mortality events in many amphibian species, resulting in at least 90 species' extinctions to date. Exposure to Bd metabolites (i.e. non-infectious antigenic chemicals released by Bd) partially protects frogs during subsequent challenges with live Bd, suggesting its use as a prophylactic treatment and potential vaccine. However, we do not know whether Bd metabolite exposure protects against strains beyond the one used for treatment. To address this knowledge gap, we conducted a 3 × 2 experiment where we exposed adult Cuban treefrogs,
Osteopilus septentrionalis
, to one of three treatments (Bd metabolites from California-isolated strain JEL-270, Panamá-isolated strain JEL-419, or an artificial spring water control) and then challenged individuals with live Bd from either strain. We found that exposure to Bd metabolites from the California-isolated strain significantly reduced Bd loads of frogs challenged with the live Panamá-isolated strain, but no other treatments were found to confer protective effects. These findings demonstrate asymmetric cross-protection of a Bd metabolite prophylaxis and suggest that work investigating multiple, diverse strains is urgently needed.
Bright green fluorescence of Asian paper wasp nests
Authors: Daney de Marcillac Willy , Nguyen Lien Thi Phuong , Aracheloff Camille , Berthier Serge , Schöllhorn Bernd
Published: August 2021

An exceptionally bright fluorescent biomatter was discovered when exploring, with UV-A light, the nests of several oriental paper wasp species of the genusPolistes, a genus of diurnal social insects. Fluorescence spectra of the cocoon cap membranes revealed narrow emission bands in the green range of the visible spectrum. Large Stokes shifts of around 160 nm and high fluorescence quantum yields of up to 35% were measured. Transmission spectra were recorded in order to estimate the contribution of the fluorescence to the visible light transmitted through the cocoon cap membrane. The nest fluorescence of the Vietnamese wasps was compared with a European and an American species. Potential biological functions of these interesting fluorescence properties of the studied biomaterial are discussed. The discovery of this striking example of a fluorescent terrestrial biomaterial may contribute to the debate on adaptive biological functions of natural fluorescence and falls in line with the growing interest in biodiversity and bio-inspiration.
Influencing dynamics on social networks without knowledge of network microstructure
Authors: Garrod Matthew , Jones Nick S.
Published: August 2021

Social network-based information campaigns can be used for promoting beneficial health behaviours and mitigating polarization (e.g. regarding climate change or vaccines). Network-based intervention strategies typically rely on full knowledge of network structure. It is largely not possible or desirable to obtain population-level social network data due to availability and privacy issues. It is easier to obtain information about individuals’ attributes (e.g. age, income), which are jointly informative of an individual’s opinions and their social network position. We investigate strategies for influencing the system state in a statistical mechanics based model of opinion formation. Using synthetic and data-based examples we illustrate the advantages of implementing coarse-grained influence strategies on Ising models with modular structure in the presence of external fields. Our work provides a scalable methodology for influencing Ising systems on large graphs and the first exploration of the Ising influence problem in the presence of ambient (social) fields. By exploiting the observation that strong ambient fields can simplify control of networked dynamics, our findings open the possibility of efficiently computing and implementing public information campaigns using insights from social network theory without costly or invasive levels of data collection.
Modular dynamic biomolecular modelling with bond graphs: the unification of stoichiometry, thermodynamics, kinetics and data
Authors: Gawthrop Peter J. , Pan Michael , Crampin Edmund J.
Published: August 2021

Renewed interest in dynamic simulation models of biomolecular systems has arisen from advances in genome-wide measurement and applications of such models in biotechnology and synthetic biology. In particular, genome-scale models of cellular metabolism beyond the steady state are required in order to represent transient and dynamic regulatory properties of the system. Development of such whole-cell models requires new modelling approaches. Here, we propose the energy-based bond graph methodology, which integrates stoichiometric models with thermodynamic principles and kinetic modelling. We demonstrate how the bond graph approach intrinsically enforces thermodynamic constraints, provides a modular approach to modelling, and gives a basis for estimation of model parameters leading to dynamic models of biomolecular systems. The approach is illustrated using a well-established stoichiometric model ofEscherichia coliand published experimental data.
Effect of non-instructed instrumental contingency of monetary reward and positive affect in a cognitive control task
Authors: Prével Arthur , Hoofs Vincent , Krebs Ruth M.
Published: August 2021

In recent years, we observed a strong interest in the influence of motivation and emotion on cognitive control. Prior studies suggest that the instrumental contingency between a response and a rewarding or affective stimulus is particularly important in that context—which is resonating with observations in the associative learning literature. However, despite this overlap, and the relevance of non-instructed learning in real life, the vast majority of studies investigating motivation–cognition interactions use direct instructions to inform participants about the contingencies between responses and stimuli. Thus, there is little experimental insight regarding how humans detect non-instructed contingencies between their actions and motivational or affective outcomes, and how these learned contingencies come to influence cognitive control processes. In an attempt to close this gap, the goal of the present study was to test the effect of non-instructed contingent and non-contingent outcomes (i.e. monetary reward and positive affective stimuli) on cognitive control using the AX-continuous performance task (AX-CPT) paradigm. We found that entirely non-instructed contingencies between responses and positive outcomes (both monetary and affective ones) led to significant performance improvement. The present results open new perspectives for studying the influence of motivation and emotion on cognitive control at the insertion with associative learning.
Habitat patches providing south–north connectivity are under-protected in a fragmented landscape
Authors: Travers Thomas J. P. , Alison Jamie , Taylor Sarah D. , Crick Humphrey Q. P. , Hodgson Jenny A.
Published: August 2021

As species’ ranges shift to track climate change, conservationists increasingly recognize the need to consider connectivity when designating protected areas (PAs). In fragmented landscapes, some habitat patches are more important than others in maintaining connectivity, and methods are needed for their identification. Here, using the Condatis methodology, we model range expansion through an adaptation of circuit theory. Specifically, we map ‘flow’ through 16 conservation priority habitat networks in England, quantifying how patches contribute to functional South–North connectivity. We also explore how much additional connectivity could be protected via a connectivity-led protection procedure. We find high-flow patches are often left out of existing PAs; across 12 of 16 habitat networks, connectivity protection falls short of area protection by 13.6% on average. We conclude that the legacy of past protection decisions has left habitat-specialist species vulnerable to climate change. This situation may be mirrored in many countries which have similar habitat protection principles. Addressing this requires specific planning tools that can account for the directions species may shift. Our connectivity-led reserve selection procedure efficiently identifies additional PAs that prioritize connectivity, protecting a median of 40.9% more connectivity in these landscapes with just a 10% increase in area.
A reassessment of the enigmatic diapsid
Paliguana whitei
and the early history of Lepidosauromorpha
Authors: Ford David P. , Evans Susan E. , Choiniere Jonah N. , Fernandez Vincent , Benson Roger B. J.
Published: August 2021

Lepidosaurs include lizards, snakes, amphisbaenians and the tuatara, comprising a highly speciose evolutionary radiation with widely varying anatomical traits. Their stem-lineage originated by the late middle Permian 259 million years ago, but its early fossil record is poorly documented, obscuring the origins of key anatomical and functional traits of the group.
Paliguana whitei
, from the Early Triassic of South Africa, is an enigmatic fossil species with the potential to provide information on this. However, its anatomy and phylogenetic affinities remain highly uncertain, and have been debated since its discovery more than 100 years ago. We present microtomographic three-dimensional imaging of the cranial anatomy of
P. whitei
that clarifies these uncertainties, providing strong evidence for lepidosauromorph affinities based on the structure of the temporal region and the implantation of marginal dentition. Phylogenetic analysis including these new data recovers
Paliguana
as the earliest known stem-lepidosaur, within a long-lived group of early diverging lepidosauromorphs that persisted to at least the Middle Jurassic. Our results provide insights into cranial evolution on the lepidosaur stem-lineage, confirming that characteristics of pleurodont dental implantation evolved early on the lepidosaur stem-lineage. By contrast, key functional traits related to hearing (quadrate conch) and feeding (streptostyly) evolved later in the lepidosaur crown-group.
Experimental manipulation of photoperiod influences migration timing in a wild, long-distance migratory songbird
Authors: Bani Assadi Saeedeh , Fraser Kevin Charles
Published: August 2021

Previous laboratory studies have demonstrated the role of photoperiod in cueing the migration timing of small land birds; however, how migration timing of young birds in wild environments develops in relation to these cues have rarely been investigated. Such investigations can make important contributions to our developing understanding of the phenotypic plasticity of migration timing to new conditions with climate change, where changes in the timing of nesting may expose juvenile birds to different photoperiods. We investigated the impact of manipulating photoperiod during nestling development in a long-distance migratory songbird on the timing of post-breeding movements in the wild. Using programmable lighting installed in the nest-boxes of purple martins (
Progne subis
), we exposed developing nestlings, from hatch to fledge date, to an extended photoperiod that matched the day length of the summer solstice in Manitoba, Canada. We found that birds with a simulated, earlier photoperiod had a longer nesting period and later fledge and autumn departure dates than control group birds. This study demonstrates the phenotypic plasticity of first-year birds to the ontogenetic effect of their hatch date in the formation of the timing of their first post-breeding movements. Further, we discuss how these results have implications for the potential use of assisted evolution approaches to alter migration timing to match new conditions with climate change.
Young chicks rely on symmetry/asymmetry in perceptual grouping to discriminate sets of elements
Authors: Loconsole Maria , De Agrò Massimo , Regolin Lucia
Published: August 2021

Grouping sets of elements into smaller, equal-sized, subsets constitutes a perceptual strategy employed by humans and other animals to enhance cognitive performance. Here, we show that day-old chicks can solve extremely complex numerical discriminations (Exp.1), and that their performance can be enhanced by the presence of symmetrical/asymmetrical colour grouping (Exp.2 versus Exp.3). Newborn chicks were habituated for 1 h to even numerosities (sets of elements presented on a screen) and then tested for their spontaneous choice among what for humans would be considered a prime and a non-prime odd numerosity. Chicks discriminated and preferred the prime over the composite set of elements irrespective of its relative magnitude (i.e. 7 versus 9 and 11 versus 9). We discuss this result in terms of novelty preference. By employing a more complex contrast (i.e. 13 versus 15), we investigated the limits of such a mechanism and showed that induced grouping positively affects chicks' performance. Our results suggest the existence of a spontaneous mechanism that enables chicks to create symmetrical (i.e. same-sized) subgroups of sets of elements. Chicks preferentially inspected numerosities for which same-sized grouping is never possible (i.e. the prime numerosity) rather than numerosities allowing for symmetrical grouping (i.e. composite).
Capnocytophaga periodontitidis sp. nov., isolated from subgingival plaque of periodontitis patient
Authors: Zhang Yifei , Qiao Dan , Shi Wenyu , Wu Danni , Cai Man
Published: August 2021

Two carbon dioxide-requiring, gliding, Gram-stain-negative strains, designated p1a2T and 051621, were isolated from subgingival plaque in association with severe periodontitis. The 16S rRNA gene sequence analysis revealed that they represented members of the genus

Capnocytophaga

and had less than 96.4 % pairwise similarity with species with validly published names in this genus. The whole-genome sequences of those strains had less than 91.9 % average nucleotide identity and 48.4 % digital DNA–DNA hybridization values with the other type strains of species of the genus

Capnocytophaga

, both below the species delineation threshold. The results of pan-genomic analysis indicated that p1a2T and 051621 shared 765 core gene families with the other ten species in this genus, and the numbers of strain-specific gene families were 493 and 455, respectively. The major fatty acids were iso-C15 : 0 and C16 : 0. A combination of phenotypic, chemotaxonomic, phylogenetic and genotypic data clearly indicate that p1a2T and 051621 should be considered to represent a novel species of the genus

Capnocytophaga

, for which the name Capnocytophaga periodontitidis sp. nov. is proposed. The type strain is p1a2T (=CGMCC 1.17337T=JCM 34126T).
Psychrosphaera ytuae sp. nov., isolated from the deep-sea cold seep sediment of South China Sea
Authors: Xu Xiu-dan , Zhang Jian , Sun Qing-lei , Sun Yuan-yuan , Tang Yong-zheng
Published: August 2021

In this study, we report a Gram-stain-negative, rod-shaped, non-pigmented, motile and aerobic bacterium named strain MTZ26T, which was isolated from deep-sea sediment sampled at a cold seep in the South China Sea. Growth of strain MTZ26T occurred at 4–40 °C (optimum, 25–30 °C), pH 6.0–10.0 (optimum, 7.0–8.0) and with 1.0–11.0 % (w/v) NaCl (optimum, 6.0–8.0 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain MTZ26T belonged to the genus

Psychrosphaera

and was closely related to

Psychrosphaera aestuarii

PSC101T (97.5 % sequence similarity) and

Psychrosphaera haliotis

KDW4T (97.5 %). Genomic analysis indicated that strain MTZ26T contains a circular chromosome of 3 331 814 bp with G+C content of 42.2 mol%. The predominant respiratory quinone of MTZ26T was ubiquinone-8. The polar lipids of MTZ26T contained phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminophospholipid and one unidentified phospholipid. The major fatty acids of strain MTZ26T contained C15:0, C16:0, C17:0, C17 : 1 ω8c, C10 : 0 3-OH, C11 : 0 3-OH, C15 : 1 ω8c and summed feature 8 (C18 : 1 ω7c or/and C18 : 1 ω6c). Results of phylogenetic, physiological, biochemical and morphological analyses suggested that strain MTZ26T represents a novel species of the genus

Psychrosphaera

, and the name Psychrosphaera ytuae sp. nov. is proposed with the type strain MTZ26T (=MCCC 1K05568T=JCM 34321T).
Evolution and emergence of multidrug-resistant Mycobacterium tuberculosis in Chisinau, Moldova
Authors: Brown Tyler S. , Eldholm Vegard , Brynildsrud Ola , Osnes Magnus , Levy Natalie , Stimson James , Colijn Caroline , Alexandru Sofia , Noroc Ecaterina , Ciobanu Nelly , Crudu Valeriu , Cohen Ted , Mathema Barun
Published: August 2021

The evolution and emergence of drug-resistant tuberculosis (TB) has been studied extensively in some contexts, but the ecological drivers of these two processes remain poorly understood. This study sought to describe the joint evolutionary and epidemiological histories of a novel multidrug-resistant

Mycobacterium tuberculosis

strain recently identified in the capital city of the Republic of Moldova (MDR Ural/4.2), where genomic surveillance of drug-resistant

M. tuberculosis

has been limited thus far. Using whole genome sequence data and Bayesian phylogenomic methods, we reconstruct the stepwise acquisition of drug resistance mutations in the MDR Ural/4.2 strain, estimate its historical bacterial population size over time, and infer the migration history of this strain between Eastern European countries. We infer that MDR Ural/4.2 likely evolved (via acquisition of rpoB S450L, which confers resistance to rifampin) in the early 1990s, during a period of social turmoil following Moldovan independence from the Soviet Union. This strain subsequently underwent substantial population size expansion in the early 2000s, at a time when national guidelines encouraged inpatient treatment of TB patients. We infer exportation of this strain and its isoniazid-resistant ancestral precursor from Moldova to neighbouring countries starting as early as 1985. Our findings suggest temporal and ecological associations between specific public health practices, including inpatient hospitalization of drug-resistant TB cases from the early 2000s until 2013, and the evolution of drug-resistant

M. tuberculosis

in Moldova. These findings underscore the need for regional coordination in TB control and expanded genomic surveillance efforts across Eastern Europe.
Irradiation of the Subventricular Zone and Subgranular Zone: an Atlas-based analysis on Overall Survival in High- and Low-Grade Glioma Patients
Authors: Bruil Danique E. , David Szabolcs , Nagtegaal Steven H.J , de Sonnaville Sophia F.A.M , Verhoeff Joost J.C.
Published: August 2021

Background

Neural stem cells in the subventricular- (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma.

Methods

We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBRA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR-images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis.

Results

Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy,p<0.001; multivariate: 1.103/Gy,p= 0.002) and SGZ dose (univariate: 1.023/Gy,p<0.001; multivariate: 1.055/Gy,p<0.001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high/low dose groups for HGG patients (SVZ: respectively 10.7 months (>30.33 Gy) vs 14.0 months (<30.33 Gy) median OS,p= 0.011; SGZ: respectively 10.7 months (>29.11 Gy) vs 15.5 months (<29.11 Gy) median OS,p<0.001). No correlations between dose and OS were not found for LGG patients.

Conclusion

Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

Key Points

Neural stem cells in the SVZ and SGZ are hypothesized to support growth of glioma.

Higher radiation doses on the SVZ and SGZ correlate with lower OS in HGG patients.

Avoidance of neurogenic niches should be considered to improve OS of HGG patients.

Importance of Study

Survival rates and quality of life of patients with glioma are still suboptimal, therefore improvement of radiation treatment planning and delivery is required. The SVZ and SGZ of the adult human brain are a source of brain tissue repair but may also be the source of glioma growth enhancement. By investigating the effects of radiotherapy on SVZ and SGZ, we gain insight into associations between tumor progression and survival. We included 273 adult patients with high- and low- grade glioma who received radiation treatment. We found that irradiation doses on neurogenic areas correlate with lower OS in patients with HGG. Avoidance of SVZ and SGZ should be considered to improve OS. These study results will contribute to optimization of brain tumor radiotherapy, focused on increasing OS. In order to facilitate future research into the role of the SVZ, we also provide stereotaxic standard space atlas labels for SVZ and SGZ.
Reduction in initiations of HIV treatment in South Africa during the COVID pandemic
Authors: Benade Mariet , Long Lawrence , Rosen Sydney , Meyer-Rath Gesine , Tucker Jeanne-Marie , Miot Jacqui
Published: August 2021

Background

In response to the global pandemic of COVID-19, countries around the world began imposing stay-at-home orders, restrictions on transport, and closures of businesses in early 2020. South Africa implemented a strict lockdown in March 2020 before its first COVID-19 wave started, gradually lifted restrictions between May and September 2020, and then re-imposed restrictions in December 2020 in response to its second wave. There is concern that COVID-19-related morbidity and mortality, fear of transmission, and government responses may have led to a reduction in antiretroviral treatment (ART) initiations for HIV-infected individuals in countries like South Africa.

Methods

We analyzed national, public sector, facility-level data from South Africa’s District Health Information System (DHIS) from January 2019 to March 2021 to quantify changes in ART initiation rates stratified by province, setting, facility size and type and compared the timing of these changes to COVID-19 case numbers and government lockdown levels. We excluded facilities with missing data, mobile clinics, and correctional facilities. We estimated the total number of ART initiations per study month for each stratum and compared monthly totals, by year.

Results

At the 2471 facilities in the final data set (59% of all ART sites in the DHIS), 28% fewer initiations occurred in 2020 than in 2019. Numbers of ART initiations declined sharply in all provinces in April-June 2020, compared to the same months in 2019, and remained low for the rest of 2020, with some recovery between COVID-19 waves in October 2020 and possible improvement beginning in March 2021. Percentage reductions were largest in district hospitals, larger facilities, and urban areas. After the initial decline in April-June 2020, most provinces experienced a clear inverse relationship between COVID-19 cases and ART initiations but little relationship between ART initiations and lockdown level.

Conclusions

The COVID-19 pandemic and responses to it resulted in substantial declines in the number of HIV-infected individuals starting treatment in South Africa, with no recovery of numbers during 2020. These delays may lead to worse treatment outcomes for those with HIV and potentially higher HIV transmission. Exceptional effort will be needed to sustain gains in combating HIV.
Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California
Authors: Servellita Venice , Sotomayor-Gonzalez Alicia , Gliwa Amelia S. , Torres Erika , Brazer Noah , Zhou Alicia , Hernandez Katherine T. , Sankaran Maddie , Wang Baolin , Wong Daniel , Wang Candace , Zhang Yueyuan , Reyes Kevin R , Glasner Dustin , Deng Xianding , Streithorst Jessica , Miller Steve , Frias Edwin , Rodgers Mary , Cloherty Gavin , Hackett John , Philip Susan , Topper Scott , Sachdev Darpun , Chiu Charles Y.
Published: August 2021

Associations between vaccine breakthrough cases and infection by SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analyzed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from February 1 to June 30, 2021, of which 125 (9.1%) were vaccine breakthrough infections. Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), but not by those associated with increased infectivity only (N501Y) (85% versus 77%, p = 0.092). Differences in viral loads were non-significant between unvaccinated and fully vaccinated persons overall (p = 0.99) and according to lineage (p = 0.09 – 0.78). Viral loads were significantly higher in symptomatic as compared to asymptomatic vaccine breakthrough cases (p < 0.0001), and symptomatic vaccine breakthrough infections had similar viral loads to unvaccinated infections (p = 0.64). In 5 cases with available longitudinal samples for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to immunocompromised state or infection by an antibody-resistant lineage. Taken together, our results suggest that vaccine breakthrough infecions are overrepresnted by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage.
Comprehensive genetic analysis of the human lipidome identifies novel loci controlling lipid homeostasis with links to coronary artery disease
Authors: Cadby Gemma , Giles Corey , Melton Phillip E , Huynh Kevin , Mellett Natalie A , Duong Thy , Nguyen Anh , Cinel Michelle , Smith Alex , Olshansky Gavriel , Wang Tingting , Brozynska Marta , Inouye Mike , McCarthy Nina S , Ariff Amir , Hung Joseph , Hui Jennie , Beilby John , Dubé Marie-Pierre , Watts Gerald F , Shah Sonia , Wray Naomi R , Lim Wei Ling Florence , Chatterjee Pratishtha , Martins Ian , Laws Simon M , Porter Tenielle , Vacher Michael , Bush Ashley I , Rowe Christopher C , Villemagne Victor L , Ames David , Masters Colin L , Taddei Kevin , Arnold Matthias , Kastenmüller Gabi , Nho Kwangsik , Saykin Andrew J , Han Xianlin , Kaddurah-Daouk Rima , Martins Ralph N , Blangero John , Meikle Peter J , Moses Eric K
Published: August 2021

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species that are putatively in the mechanistic pathway to coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 phenotyped individuals from the Busselton Health Study. In our discovery GWAS we identified 667 independent loci associations with these lipid species (479 novel), followed by meta-analysis and validation in two independent cohorts. Lipid endophenotypes (134) identified for CAD were associated with variation at 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P<1×10−3), 43 loci were associated with at least one of the 134 lipid endophenotypes. The findings of this study illustrate the value of integrative biology to investigate the genetics and lipid metabolism in the aetiology of atherosclerosis and CAD, with implications for other complex diseases.
A multidimensional Mendelian randomization study on the impact of gut dysbiosis on chronic diseases and human longevity
Authors: Gagnon Éloi , Mitchell Patricia L. , Manikpurage Hasanga , Abner Erik , Taba Nele , Esko Tõnu , Ghodsian Nooshin , Thériault Sébastien , Mathieu Patrick , Arsenault Benoit J.
Published: August 2021

Alterations of the gut microbiota, often referred to as gut dysbiosis, have been associated with several chronic diseases and longevity in pre-clinical models as well as in observational studies. Whether these relationships underlie causal associations in humans remains to be established. We aimed to determine whether gut dysbiosis influences the risk of chronic diseases and longevity using a comprehensive 2-Sample Mendelian randomization (2SMR) approach. We included as exposures inflammatory bowel disease (IBD) as a human model of gut dysbiosis, 11 gut-associated metabolites and pathways and 48 microbial taxa. Study outcomes included eight chronic diseases previously linked with gut dysbiosis using observational studies (Alzheimer’s disease, depression, type 2 diabetes, non-alcoholic fatty liver disease, coronary artery disease (CAD), stroke, osteoporosis and chronic kidney disease) as well as parental longevity and life expectancy. Neither IBD, nor gut-associated metabolites were causally associated with chronic disease or lifespan. After multiple testing correction for 582 tests, no microbial taxa-chronic disease associations remained significant. After robustness analyses and multivariate MR to correct for body mass index and alcohol intake on all 42 nominally significant causal relationships, four associations remained. Altogether, results of this multidimensional Mendelian randomization study suggest that gut dysbiosis has little impact on chronic diseases and human longevity and that previous documented associations may not underly causal relationships. Studies with larger sample sizes and more optimal taxonomic discrimination may ultimately be required to determine whether the human gut microbiota plays a causal role in the etiology of chronic diseases and longevity.
A composite biomarker for esophageal cancer risk from automated analysis of a non-endoscopic device
Authors: Berman Adam G. , Fitzgerald Rebecca C. , Markowetz Florian
Published: August 2021

Barrett’s esophagus containing intestinal metaplasia predisposes to cancer, yet the majority of cases are undiagnosed. The length of a Barrett’s segment is a key indicator of cancer risk, but measuring it has so far relied on endoscopy, which is expensive and invasive. Cytosponge-TFF3 is a minimally-invasive test that identifies intestinal metaplasia for endoscopic confirmation. We report a machine learning technique to quantify the extent of intestinal metaplasia and predict Barrett’s segment length from whole-slide image tile counts automatically generated from Cytosponge-TFF3 histology slides. Utilizing data from 529 patients, our segment length prediction model achieves an average validation fold accuracy of 0.84. Applying this algorithm to an independent test set of 162 patients from a screening trial shows a precision of 0.90 for identifying short-segment disease. This advance will enable higher-risk patients to be prioritized for endoscopy while saving more than half of Cytosponge-TFF3-positive patients from endoscopy in the screening setting.
COVID-19 and Vitamin D (Co-VIVID Study): a systematic review and meta-analysis of randomized controlled trials
Authors: Varikasuvu Seshadri Reddy , Thangappazham Balachandar , Raj Hemanth
Published: August 2021

Background

Vitamin D levels have been reported to be associated with COVID-19 susceptibility, severity and mortality events.. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the use of vitamin D intervention on COVID-19 outcomes.

Methods

Literature search was conducted using PubMed, Cochrane library, and ClinicalTrials.gov databases (latest search on August 5, 2021). We included RCTs reporting the use of vitamin D intervention to control/placebo group in COVID-19. Two independent researchers did literature search, abstracted data, and the risk of bias assessment.

Results

A total of 6 RCTs with 551 COVID-19 patients were included. The overall collective evidence pooling all the outcomes across all RCTs indicated the beneficial use of vitamin D intervention in COVID-19 (relative risk, RR = 0.60, 95% CI 0.40 to 0.92, Z=2.33, p=0.02, I2 = 48%). However, no statistical significance was observed for individual outcomes of ICU care (RR = 0.11, 95% CI 0.15 to 1.30, Z=1.48, p=0.14, I2 = 66%) and mortality (RR = 0.78, 95% CI 0.25 to 2.40, Z=0.66, p=0.02, I2 = 33%), though decreased rates were noted. The rates of RT-CR positivity was significantly decreased in the intervention group as compared to the non-vitamin D groups (RR = 0.46, 95% CI 0.24 to 0.89, Z=2.31, p=0.02, I2 = 0%).

Conclusion

COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events and RT-PCR positivity. However, no statistical significance has been achieved for individual outcomes of ICU and deaths. More RCTs and completion of ongoing trials largely needed to precisely establish the association between vitamin D use and COVID-19.
A Lagrangian Approach Towards Quantitative Analysis Of Flow-mediated Infection Transmission In Indoor Spaces With Application To SARS-COV-2
Authors: Wilson Joseph , Miller Shelly L. , Mukherjee Debanjan
Published: August 2021

The ongoing SARS-CoV-2 (Covid-19) pandemic has ushered an unforeseen level of global health and economic burden. As a respiratory infection, Covid-19 is known to have a dominant airborne transmission modality, wherein fluid flow plays a central role. Quantification of complex non-intuitive dynamics and transport of pathogen laden respiratory particles in indoor flows has been of specific interest. Here we present a Lagrangian computational approach towards quantification of human-to-human exposure quantifiers, and identification of pathways by which flow organizes transmission. We develop a Lagrangian viral exposure index in a parametric form, accounting for key parameters such as building and layout, ventilation, occupancy, biological variables. We also employ a Lagrangian computation of the Finite Time Lyapunov Exponent field to identify hidden patterns of transport. A systematic parametric study comprising a set of 120 simulations, yielding a total of 1,320 different exposure index computations are presented. Results from these simulations enable: (a) understanding the otherwise hidden ways in which air flow organizes the long-range transport of such particles; and (b) translating the micro-particle transport data into a quantifier for understanding infection exposure risks.
A conformational variant of p53 (U-p53AZ) as blood-based biomarker for the prediction of the onset of symptomatic Alzheimer’s disease
Authors: Piccirella Simona , Van Neste Leander , Fowler Christopher , Masters Colin L , Fripp Jurgen , Doecke James D. , Xiong Chengjie , Uberti Daniela , Kinnon Paul
Published: August 2021

Background

Ongoing research seeks to identify blood-based biomarkers able to predict the onset and progression of Alzheimer’s disease (AD). A potential biomarker is the unfolded conformational variant of p53, previously observed in individuals in the prodromal and clinical AD stages. In this retrospective study, we compare diagnostic and prognostic performances of measures of the amyloid β load with those of a conformational variant of U-p53 in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort.

Methods

Immunoprecipitation (IP) followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS) and protein sequencing in plasma samples from the AIBL study identified the clinically relevant AZ 284®peptide, representing a measure of the U-p53 conformational variant (U-p53AZ). Based on U-p53AZquantification via IP/LC electrospray ionisation-coupled MS/MS (AlzoSure®Predict test) on 515 samples from 482 individuals from the AIBL cohort, the predictive performance of U-p53AZwas assessed and compared with amyloid load as measured by amyloid β-positron emission tomography (Aβ-PET). Its predictive performance was determined at 36, 54, 72 and 90 months following baseline assessment.

Results

U-p53AZwas able to identify individuals with AD dementia with an area under the receiver operating characteristic curve (AUC) of 99%. U-p53AZoutperformed the conventional Aβ-PET measures in predicting the onset of AD dementia both from preclinical (AUC=98%) and prodromal stages (AUC=89%), even 90 months prior to onset (AUC=99%). Additionally, the estimated predictive performance of U-p53AZwas superior (AUC ≥98%) to other risk factors (i.e., gender, Aβ-PET andAPOEε4 allele status) in identifying individuals at high risk for progression to AD.

Conclusion

These findings support use of U-p53AZas blood-based biomarker predicting if individuals, at both asymptomatic and MCI stages, would progress to AD at least six years prior to the onset of clinical AD dementia.
Loss of nucleoporin Nup50 is a risk factor for amyotrophic lateral sclerosis
Authors: Megat Salim , Mora Natalia , Sanogo Jason , Catanese Alberto , Alami Najwa Ouali , Freischmidt Axel , Mingaj Xhuljana , de Calbiac Hortense , Muratet François , Dirrig-Grosch Sylvie , Dieterle Stéphane , Van Bakel Nick , Müller Kathrin , Sieverding Kirsten , Weishaupt Jochen , Andersen Peter Munch , Weber Markus , Neuwirth Christoph , Margelisch Markus , Sommacal Andreas , van Eijk Kristel R. , Veldink Jan H ,   Project Mine ALS sequencing consortium, Lautrette Géraldine , Couratier Philippe , Boeckers Tobias , Ludolph Albert C. , Roselli Francesco , Yilmazer-Hanke Deniz , Millecamps Stéphanie , Kabashi Edor , Storkebaum Erik , Sellier Chantal , Dupuis Luc
Published: August 2021

The genetic basis of amyotrophic lateral sclerosis (ALS) is still incompletely understood. Using two independent genetic strategies, we show here that a large part of ALS heritability lies in genes expressed in inhibitory and excitatory neurons, especially at splicing sites regulated by a defined set of RNA binding proteins including TDP-43 and FUS. We conducted a transcriptome wide association study (TWAS) and identified 59 loci associated with ALS, including 14 previously identified genes, some of them not previously reaching significance in genome wide association studies. Among the 45 novel genes, several genes are involved in pathways known to be affected in ALS such as mitochondrial metabolism (including ATP5H, ATP5D, BCS1L), proteostasis (including COPS7A, G2E3, TMEM175, USP35) or gene expression and RNA metabolism (including ARID1B, ATXN3, PTBP2, TAF10). Interestingly, decreased expression of NUP50, a constrained gene encoding a nuclear pore basket protein, was associated with ALS in TWAS (Zscore = −4, FDR = 0.034). 11 potentially pathogenic variants (CADD score > 20) in 23 patients were identified in the NUP50 gene, most of them in the region of the protein mediating interaction with Importin alpha, and including 2 frameshift mutations. In cells from two patients carrying NUP50 variants, we showed decreased levels of NUP50 protein. Importantly, knocking down Nup50 led to increased neuronal death associated with p62 and nucleoporin inclusions in cultured neurons, and motor defects in Drosophila and zebrafish models. In all, our study identifies alterations in splicing in neurons as a critical pathogenic process in ALS, uncovers several new loci potentially contributing to ALS missing heritability, and provides genetic evidence linking nuclear pore defects to ALS.