bluuebunny/crossref_metadata_2025 huggingface dataset:
L’évaluation et l’optimisation de la santé osseuse chez les enfants ayant des affections chroniques
Authors: Rodd Celia , Kirouac Nicole , Orkin Julia , Grimes Ruth
Published: July 2022

R!sum!

Les professionnels de la santé des enfants jouent un rôle important dans l’optimisation de la santé osseuse. Il est essentiel d’intervenir rapidement pour maximiser le pic de masse osseuse à l’adolescence et au début de l’âge adulte et d’ainsi réduire le risque d’ostéoporose et de fractures plus tard dans la vie. Les enfants et les adolescents ayant une affection chronique peuvent présenter plusieurs facteurs de risque de mauvaise santé osseuse, notamment des maladies inflammatoires sous-jacentes, des activités avec mise en charge limitées, un retard pubertaire et un apport insuffisant de calcium et de vitamine D. Certains médicaments, et particulièrement les glucocorticoïdes, peuvent compromettre la masse osseuse et exposer l’enfant à un risque de fractures de fragilisation. Le présent point de pratique décrit une approche ciblée pour déterminer les facteurs de risque liés à la santé osseuse chez les enfants et les adolescents ayant une affection chronique, expose les mesures à prendre en cabinet pour optimiser l’acquisition de la masse osseuse et propose des outils en ligne utiles et des références médicales à l’intention des professionnels de la santé des enfants. Les indications pour diriger les patients vers un spécialiste de la santé osseuse et pour procéder à des interventions pharmacologiques visant les os sont également abordées.
Evaluating and optimizing bone health in children with chronic health conditions
Authors: Rodd Celia , Kirouac Nicole , Orkin Julia , Grimes Ruth
Published: July 2022

Paediatric health care providers (HCPs) play an important role in optimizing bone health. Early intervention is essential to maximize the accrual of peak bone mass in adolescence and young adulthood and to reduce osteoporosis and fracture risk later in life. Children and adolescents with chronic health conditions may have several risk factors for poor bone health, including underlying inflammatory conditions, reduced weight-bearing activity, delayed puberty, and inadequate intake of calcium and vitamin D. Some medications—particularly glucocorticoids—can compromise bone mass and place a child at risk for fragility fractures. This practice point describes a targeted approach to identifying bone health risk factors in children and youth with chronic health conditions, highlights office initiatives aimed at optimizing bone mass accrual, and links HCPs to useful web-based tools and medical references. Indications for referral to a bone health specialist and bone-specific pharmacotherapeutic interventions are also reviewed.
Does increased springtime solar radiation also increase primary production?
Authors: Shinohara Ryuichiro , Matsuzaki Shin-Ichiro S , Nakagawa Megumi , Tsuchiya Kenji , Kohzu Ayato
Published: July 2022

We tested the hypothesis that long-term brightening of solar radiation and changes in the underwater light climate would increase the primary production of phytoplankton in the springtime in Lake Kasumigaura, Japan. Global solar radiation fluctuates on a decadal scale, and the solar radiation in May has been increasing since the 1990s in Japan. We developed a model of depth-integrated primary production (gC m−2 h−1) based on long-term monitoring data. The model based on photosynthesis-irradiance curve clarified that primary production increased by 13.2%, from 0.093 gC m−2 h−1 in 1992 to 0.105 gC m−2 h−1 in 2019, because of the combined effects of solar radiation and water temperature increases. Sensitivity analysis of the model showed that primary production was most sensitive to water quality parameters, i.e. the light attenuation coefficient and nutrient effects on Pmax. Nutrient effects were significantly correlated with the particulate organic carbon to nitrogen ratio, indicating that nitrogen shortage in phytoplankton cells may affect primary production. These results suggest that long-term springtime increases in solar radiation and water temperature increase primary production, but that water quality also controls primary production.
Rectosigmoid Cancer—Rectal Cancer or Sigmoid Cancer?
Authors: Hui Caressa , Baclay Richel , Liu Kevin , Sandhu Navjot , Loo Phoebe , von Eyben Rie , Chen Chris , Sheth Vipul , Vitzthum Lucas , Chang Daniel , Pollom Erqi
Published: July 2022

Objectives:

We aimed to determine the optimal treatment for patients with locally advanced rectosigmoid cancers, and to determine whether this can be guided by distance from anal verge (AV) and/or anatomic landmarks such as the sacral promontory and peritoneal reflection (PR).

Materials and Methods:

We retrospectively reviewed patients with T3-T4 and/or node-positive rectosigmoid cancers who underwent surgery from 2006 to 2018 with available pelvic imaging. We included tumors at 9 to 20 cm from the AV on either staging imaging, or colonoscopy. Patients were stratified into those who received neoadjuvant therapy, and those who underwent upfront surgery. Comparisons of characteristics were performed using χ2 test and Fischer exact test. Locoregional failure (LRF) and overall survival were compared using Cox regressions and Kaplan-Meier analysis.

Results:

One hundred sixty-one patients were included. Ninety-seven patients had neoadjuvant therapy, and 64 patients had upfront surgery. Median follow-up time was 45.1 months. Patients who had neoadjuvant therapy had tumors that were higher cT stage (P<0.01) with more positive/close circumferential resection margins seen on imaging by radiologists (28.9% vs. 1.6%, P=0.015). The 2-year rate of LRF, distant metastases, or overall survival was not significantly different between the 2 groups. None of 15 patients with tumors below the PR treated with neoadjuvant therapy had LRF, but 1 (25%) of 4 patients with tumors below the PR treated with adjuvant therapy experienced LRF (P=0.05).

Conclusions:

Patients with tumors below the PR may benefit more from neoadjuvant therapy. The PR on imaging may be a reliable landmark in addition to the distance from the AV to determine the most appropriate treatment option.
9p24.1 Genetic Alteration and PD-L1 Expression Are Characteristic of De Novo and Methotrexate-associated Epstein-Barr Virus–positive Hodgkin Lymphoma, But Not Methotrexate-associated Hodgkin-like Lesions
Authors: Shiraiwa Sawako , Kikuti Yara Yukie , Carreras Joaquim , Kondo Yusuke , Ohmachi Ken , Ogawa Yoshiaki , Kawada Hiroshi , Sato Shinji , Gion Yuka , Sato Yasuharu , Nakamura Naoya , Ando Kiyoshi
Published: July 2022

Although the alteration of the 9p24.1 chromosome locus and PD-L1 overexpression is found in nodular sclerosis classic Hodgkin lymphoma, whether these aberrations occur in CHL and Hodgkin-like lesion (HLL) of methotrexate-associated lymphoproliferative disorder (MTX-CHL and MTX-HLL) is unknown. We compared the clinicopathologic features, the genomic status of the 9p24.1 locus and PD-L1 expression in a series of 34 patients including 17 with Epstein-Barr virus–positive de novo CHL, 7 with MTX-CHL, 10 with MTX-HLL using an immunofluorescence in situ hybridization method and immunohistochemistry. The proportions of cells with 9p24.1 genetic alteration in CD30-positive Hodgkin/Reed-Sternberg cells of de novo CHL, MTX-CHL and MTX-HLL were 55%, 68%, and 24%, respectively. The positive rates of PD-L1 measured by immunohistochemical H-scores of de novo CHL, MTX-CHL and MTX-HLL were 142±38, 157±75, and 70±42, respectively. Alteration of the 9p24.1 gene and expression of PD-L1 protein were correlated with all 3 diseases (correlation coefficient, 0.731). Both alteration of the 9p24.1 gene and overexpression of PD-L1 protein were observed in Epstein-Barr virus–positive de novo CHL and MTX-CHL but not in MTX-HLL. In conclusion, MTX-CHL has similar pathogenesis-like de novo CHL, but MTX-HLL seems to be a different disease from de novo CHL and MTX-CHL.
High-level dolutegravir resistance can emerge rapidly from few variants and spread by recombination: implications for integrase strand transfer inhibitor salvage therapy
Authors: Huik Kristi , Hill Shawn , George Jomy , Pau Alice , Kuriakose Safia , Lange Camille M. , Dee Nicola , Stoll Pamela , Khan Muhammad , Rehman Tauseef , Rehm Catherine A. , Dewar Robin , Grossman Zehava , Maldarelli Frank
Published: July 2022

The integrase strand transfer inhibitor (INSTI) dolutegravir is commonly used in combination antiretroviral therapy regimens and retains strong potency even with primary resistance mutations to some other INSTIs. Acquisition of accessory mutations to primary mutations results in significant increases in dolutegravir resistance. Previously, we reported that addition of the secondary mutation T97A can result in rapid treatment failure in individuals with INSTI mutations at positions 140 and 148. Here, we conducted a detailed case study of one of these individuals and find that T97A-containing HIV emerged from a large replicating population from only a few (≤4) viral lineages. When combined with primary INSTI resistance mutations, T97A provides a strong selective advantage; the finding that T97A-containing variants spread by replication and recombination, and persisted for months after discontinuing dolutegravir, has important implications as dolutegravir is rolled out worldwide.
Impact of preexisting nucleos(t)ide reverse transcriptase inhibitor resistance on the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide in treatment experience patients
Authors: Micán Rafael , de Gea Grela Alejandro , Cadiñanos Julen , de Miguel Rosa , Busca Carmen , Bernardino Jose I. , Valencia Eulalia , Montes Maria Luisa , Montejano Rocío , Moreno Victoria , Pérez Valero Ignacio , Serrano Lucía , González-García Juan , Arribas Jose R. , Martín-Carbonero Luz
Published: July 2022

Introduction:

Few clinical trials and cohort studies have evaluated the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV (PWH) with preexisting M184V/I or other nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs). Real-world data are also scarce.

Methods:

Retrospective review of treatment-experienced patients who started B/F/TAF in a cohort of PWH. HIV-RNA less than 50 copies/ml was analyzed at 48 weeks in an intention-to-treat (ITT) analysis (missing=failure) and per protocol analysis (patients with missing data or changes for reasons other than virological failure were excluded). Results were compared in patients with and without previous NRTI-RAMs.

Results:

Five hundred and six PWH were included (16.2% women). Median age and time with HIV infection were 52.3 and 18.9 years, respectively. At baseline, viral load was less than 50 copies/ml in 440 patients (86.6%). Overall, 69 (13.6%) participants had documented preexisting NRTI-RAMs: 57 (11.2%) M184V/I and 30 (5.9%) tenofovir RAMs. In the ITT analysis, 83% (420/506) had HIV-RNA less than 50 copies/ml [82.2% (359/437) and 88.4% (61/69) in persons without and with NRTI-RAMs, respectively (P = 0.2)]. In the per protocol analysis 94.2% (420/445) had HIV-RNA less than 50 copies/ml [94.4% (359/380) vs. 93.8% (61/65); P = 0.2]. A total of 61 participants were excluded from the per protocol analysis (23 missing data, 19 discontinued B/F/TAF because of toxicity, 13 for other reasons, and 6 died).

Conclusion:

Switching to B/F/TAF is well tolerated and effective in the real-world setting, even in patients with preexisting NRTI RAMs, such as M184V and RAMs conferring resistance to tenofovir. These results confirm the robustness of this combination.
Prevalence and risk factors of nonalcoholic steatohepatitis with significant fibrosis in people with HIV
Authors: Michel Maurice , Labenz Christian , Wahl Alisha , Anders Malena , Armandi Angelo , Huber Yvonne , Galle Peter R. , Sprinzl Martin , Schattenberg Jörn M.
Published: July 2022

Objective:

Metabolic risk factors and nonalcoholic fatty liver disease (NAFLD) in people with HIV (PWH) have been increasing. Patients exhibiting the inflammatory subtype nonalcoholic steatohepatitis (NASH) are at increased risk of liver-related complications. Therefore, the aim was to investigate the prevalence of NASH with significant fibrosis in PWH using noninvasive tests (NITs).

Design:

In this prospectively enrolling cohort study, 282 PWH were explored for hepatic steatosis, fibrosis and steatohepatitis using vibration-controlled transient elastography (VCTE) and the Fibroscan-AST (FAST) score.

Methods:

On the basis of controlled attenuation parameter (CAP; dB/m) and liver stiffness measurement (LSM; kPa), patients were categorized according to the presence of steatosis (≥275 dB/m) and significant fibrosis (≥8.2 kPa). The FAST score was calculated according to established cut-offs.

Results:

The prevalence of hepatic steatosis in this cohort was 35.5% (n = 100) with 75 (75%) of these patients fulfilling the criteria of NAFLD. The prevalence of significant fibrosis (≥ F2) was 6.7% (n = 19). The FAST score identified a total of 32 (12.3%) patients with a cut-off greater than 0.35, of whom 28 (87.5%) PWH qualified as NASH. On multivariable analysis, waist circumference was a predictor of hepatic steatosis and type 2 diabetes was a predictor of significant fibrosis. Type 2 diabetes and ALT remained independent predictors of a FAST score greater than 0.35.

Conclusion:

NASH with significant fibrosis is highly prevalent among PWH. The FAST score may be helpful to identify patients at risk for significant liver disease.
Long and persistent COVID-19 in patients with hematologic malignancies: from bench to bedside
Authors: Laracy Justin C. , Kamboj Mini , Vardhana Santosha A.
Published: July 2022

Purpose of review

Cancer patients, especially those with hematologic malignancies, are at increased risk for coronavirus disease 2019 (COVID-19)-related complications and mortality. We describe the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 infection in patients with hematologic malignancies.

Recent findings

The syndrome of persistent COVID-19 in patients with hematologic malignancies manifests as a chronic protracted illness marked by waxing and waning or progressive respiratory symptoms and prolonged viral shedding. Immunosuppressed patients with lymphoid malignancies may serve as partially immune reservoirs for the generation of immune-evasive viral escape mutants.

Persistent COVID-19 infection is a unique concern in patients with hematologic malignancies. While vaccination against severe acute respiratory syndrome coronavirus 2 has reduced the overall burden of COVID-19 in patients with hematologic cancers, whether vaccination or other novel treatments for COVID-19 prevent or alleviate this syndrome remains to be determined.
Mitigation of nontuberculous mycobacteria in hospital water: challenges for infection prevention
Authors: Kaul Christina M. , Chan Justin , Phillips Michael S.
Published: July 2022

Purpose of review

The purpose of this review is to summarize recent literature on nontuberculous mycobacteria in water of healthcare systems. Despite improvement in identification techniques and emergence of infection prevention and control programs, nontuberculous mycobacteria remain present in hospital water systems, causing outbreaks and pseudo-outbreaks in healthcare settings.

Recent findings

Waterborne outbreaks and pseudo-outbreaks of nontuberculous mycobacteria continue to affect hospitals. Improvements in methods of identification and investigation, including MALDI-TOF and whole genome sequencing with evaluation of single nucleotide polymorphisms, have been used successfully in outbreak and pseudo-outbreak investigations. Recent studies have shown control of outbreaks in immunocompromised patients through the use of sterile water for consumption, as well as control of pseudo-outbreaks by using sterile water for procedures. Construction activities have been implicated in outbreaks and pseudo-outbreaks of nontuberculous mycobacteria. Water management programs are now required by the Joint Commission, which will likely improve water risk mitigation.

Improvement in detection and identification of nontuberculous mycobacteria has led to increasing recognition of waterborne outbreaks and pseudo-outbreaks. Water management programs are of vital importance in infection prevention.
Monoclonal antibodies for prophylaxis and treatment of respiratory viral infections
Authors: Boonyaratanakornkit Jim , Boeckh Michael , Waghmare Alpana
Published: July 2022

Purpose of review

Monoclonal antibody (mAb) administration represents an important strategy for preventing and treating respiratory viral infections in vulnerable populations, including immunocompromised individuals. The purpose of this review is to provide an overview of mAbs in clinical use against respiratory viruses, highlight factors that modulate mAb clinical efficacy, and provide a perspective on future innovations in the field. This review focuses on publications from the last year.

Recent findings

Historically, clinical development of a single mAb has taken over a decade. The COVID-19 pandemic has demonstrated that this timeframe can be reduced to less than a year and has catalyzed rapid innovations in the field. Several novel mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization by the Food and Drug Administration (FDA) for the early treatment of mild to moderate COVID-19. However, the majority of these mAbs have ultimately failed due to the emergence of variants, highlighting an important lesson about predicting and countering resistance. Novel mAbs are also in clinical use or in late-stage development for the prevention of infection by SARS-CoV-2 and respiratory syncytial virus (RSV) in vulnerable populations. Several factors can be modulated to improve the clinical efficacy of mAbs. For example, Fc modifications can extend mAb half-life and increase respiratory tract bioavailability, both of which are attractive properties for achieving protection against respiratory viruses.

The mAb landscape is rapidly evolving with numerous examples of success and failure. The armamentarium of clinically-available mAbs to protect vulnerable populations is expected to undergo continued growth.
Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding
Authors: Hazelton Joshua P. , Ssentongo Anna E. , Oh John S. , Ssentongo Paddy , Seamon Mark J. , Byrne James P. , Armento Isabella G. , Jenkins Donald H. , Braverman Maxwell A. , Mentzer Caleb , Leonard Guy C. , Perea Lindsey L. , Docherty Courtney K. , Dunn Julie A. , Smoot Brittany , Martin Matthew J. , Badiee Jayraan , Luis Alejandro J. , Murray Julie L. , Noorbakhsh Matthew R. , Babowice James E. , Mains Charles , Madayag Robert M. , Kaafarani Haytham M.A. , Mokhtari Ava K. , Moore Sarah A. , Madden Kathleen , Tanner Allen , Redmond Diane , Millia David J. , Brandolino Amber , Nguyen Uyen , Chinchilli Vernon , Armen Scott B. , Porter John M.
Published: July 2022

Objective:

The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients.

Background:

Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality.

Methods:

We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications.

Results:

A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P<0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients (P<0.0001).

Conclusions:

Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.
Frontal waves and transmissions for temporal laminates and imperfect chiral interfaces
Authors: Movchan A. B. , Movchan N. V. , Jones I. S. , Milton G. W. , Nguyen H.-M.
Published: July 2022

The analysis of wave patterns in a structure which possesses periodicity in the spatial and temporal dimensions is presented. The topic of imperfect chiral interfaces is also considered. Although causality is fundamental for physical processes, natural wave phenomena can be observed when a wave is split at a temporal interface. A wave split at a spatial interface is a more common occurrence; however, when the coefficients of the governing equations are time-dependent, the temporal interface becomes important. Here, the associated frontal waves are studied, and regimes are analysed where the growth of the solution in time is found. Imperfect interfaces, across which the displacements are discontinuous, are also considered in the vector case of chiral elastic systems. Analytical study and asymptotic approximations are supplied with illustrative numerical examples.

This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
Buckling versus unilateral constraint for a multistable metamaterial element
Authors: Hima N. , Bigoni D. , Dal Corso F.
Published: July 2022

A structural element is designed and investigated, forming the basis for the development of an elastic multistable metamaterial. The leitmotif of the structural design is the implementation of a strut characterized by a bifurcation occurring at either vanishing tensile or compressive load. It is shown that buckling at null load leads to a mechanical equivalence with a unilateral constraint formulation, introducing shocks in dynamics. Towards a future analysis of the latter, the nonlinear quasi-static response is investigated, showing the multistable character of the structure, which may appear as bistable or tetrastable.

This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
Fitness costs of CRISPR-Cas systems in bacteria
Authors: Zaayman Michael , Wheatley Rachel M.
Published: July 2022

CRISPR-Cas systems provide bacteria with both specificity and adaptability in defence against invading genetic elements. From a theoretical perspective, CRISPR-Cas systems confer many benefits. However, they are observed at an unexpectedly low prevalence across the bacterial domain. While these defence systems can be gained horizontally, fitness costs may lead to selection against their carriage. Understanding the source of CRISPR-related fitness costs will help us to understand the evolutionary dynamics of CRISPR-Cas systems and their role in shaping bacterial genome evolution. Here, we review our current understanding of the potential fitness costs associated with CRISPR-Cas systems. In addition to potentially restricting the acquisition of genetic material that could confer fitness benefits, we explore five alternative biological factors that from a theoretical perspective may influence the fitness costs associated with CRISPR-Cas system carriage: (1) the repertoire of defence mechanisms a bacterium has available to it, (2) the potential for a metabolic burden, (3) larger-scale population and environmental factors, (4) the phenomenon of self-targeting spacers, and (5) alternative non-defence roles for CRISPR-Cas.
Evolution of horizontal transmission in antimicrobial resistance plasmids
Authors: Dimitriu Tatiana
Published: July 2022

Mobile genetic elements (MGEs) are one of the main vectors for the spread of antimicrobial resistance (AMR) across bacteria, due to their ability to move horizontally between bacterial lineages. Horizontal transmission of AMR can increase AMR prevalence at multiple scales, from increasing the prevalence of infections by resistant bacteria to pathogen epidemics and worldwide spread of AMR across species. Among MGEs, conjugative plasmids are the main contributors to the spread of AMR. This review discusses the selective pressures acting on MGEs and their hosts to promote or limit the horizontal transmission of MGEs, the mechanisms by which transmission rates can evolve, and their implications for limiting the spread of AMR, with a focus on AMR plasmids.
Ad26.COV2.S priming provides a solid immunological base for mRNA-based COVID-19 booster vaccination
Authors: Geers Daryl , Sablerolles Roos S.G. , van Baarle Debbie , Kootstra Neeltje A. , Rietdijk Wim J.R. , Schmitz Katharina S. , Bogers Susanne , Gommers Lennert , Nieuwkoop Nella J. , van Dijk Laura L.A. , van Haren Eva , Lafeber Melvin , Dalm Virgil A.S.H. , Goorhuis Abraham , Postma Douwe F. , Visser Leo G. , Huckriede Anke L.W. , Sette Alessandro , Grifoni Alba , de Swart Rik L. , Koopmans Marion P.G. , van der Kuy P. Hugo M. , GeurtsvanKessel Corine H. , de Vries Rory D.
Published: July 2022

A large proportion of the global population received a single dose of the Ad26.COV2.S coronavirus disease-2019 (COVID-19) vaccine as priming vaccination, which was shown to provide protection against moderate to severe COVID-19. However, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants that harbor immune-evasive mutations in the spike protein led to the recommendation of booster vaccinations after Ad26.COV2.S priming. Recent studies showed that heterologous booster vaccination with an mRNA-based vaccine following Ad26.COV2.S priming leads to high antibody levels. However, how heterologous booster vaccination affects other functional aspects of the immune response remains unknown. Here, we performed immunological profiling on samples obtained from Ad26.COV2.S-vaccinated individuals before and after a homologous (Ad26.COV2.S) or heterologous (mRNA-1273 or BNT162b2) booster vaccination. Both homologous and heterologous booster vaccination increased antibodies with multiple functionalities towards ancestral SARS-CoV-2, the Delta and Omicron BA.1 variants. Especially, mRNA-based booster vaccination induced high levels of neutralizing antibodies and antibodies with various Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. In contrast, T cell responses were similar in magnitude following homologous or heterologous booster vaccination, and retained functionality towards Delta and Omicron BA.1. However, only heterologous booster vaccination with an mRNA-based vaccine led to the expansion of SARS-CoV-2-specific T cell clones, without an increase in the breadth of the T cell repertoire as assessed by T cell receptor sequencing. In conclusion, we show that Ad26.COV2.S priming vaccination provides a solid immunological base for heterologous boosting with an mRNA-based COVID-19 vaccine, increasing humoral and cellular responses targeting newly emerging variants of concern.

One sentence summary

Ad26.COV2.S priming provides a solid immunological base for extension of cellular and humoral immune responses following an mRNA-based booster.
Optimization of energy and time determines dynamic speeds for human walking
Authors: Carlisle R. Elizabeth , Kuo Arthur D.
Published: July 2022

Humans make a number of choices when they walk, such as how fast and for how long. The preferred steady walking speed seems chosen to minimize energy expenditure per distance traveled. But the speed of actual walking bouts is not only steady, but rather a time-varying trajectory, which can also be modulated by task urgency or an individual’s movement vigor. Here we show that speed trajectories and durations of human walking bouts are explained better by an objective to minimize Energy and Time, meaning the total work or energy to reach destination, plus a cost proportional to bout duration. Applied to a computational model of walking dynamics, this objective predicts dynamic speed vs. time trajectories with inverted U shapes. Model and human experiment (N= 10) show that shorter bouts are unsteady and dominated by the time and effort of accelerating, and longer ones are steadier and faster due to energy-per-distance. Individual-dependent vigor may be characterized by the energy one is willing to spend to save a unit of time, which explains why some may walk faster than others, but everyone may have similar-shaped trajectories due to similar walking dynamics. Tradeoffs between energy and time costs can predict transient, steady, and vigor-related aspects of walking.
Complementary biological and computational approaches identify distinct mechanisms of chlorpyrifos versus chlorpyrifos oxon induced dopaminergic neurotoxicity
Authors: Sammi Shreesh Raj , Syeda Tauqeerunnisa , Conrow Kendra D. , Leung Maxwell C. K. , Cannon Jason R.
Published: July 2022

Organophosphate (OP) pesticides are widely used in agriculture. While acute cholinergic toxicity has been extensively studied, chronic effects on other neurons are less understood. Here, we demonstrated that the OP pesticide chlorpyrifos (CPF) and its oxon metabolite are dopaminergic neurotoxicants in Caenorhabditis elegans. CPF treatment led to inhibition of mitochondrial complex II, II + III, and V in rat liver mitochondria, while CPF oxon did not (complex II + III, and IV inhibition observed only at high doses). While the effect on C. elegans cholinergic behavior was mostly reversible with toxicant washout, dopamine-associated deficits persisted, suggesting dopaminergic neurotoxicity was irreversible. CPF reduced the mitochondrial content in a dose-dependent manner and the fat modulatory genes cyp-35A2 and cyp-35A3 were found to have a key role in CPF neurotoxicity. These findings were consistent with in vitro effects of CPF and CPF oxon on nuclear receptor signaling and fatty acid/steroid metabolism observed in ToxCast assays. Two-way hierarchical analysis revealed in vitro effects on estrogen receptor (ER,) pregnane X receptor (PXR), and peroxisome proliferator-activated receptor gamma (PPAR gamma) pathways as well as neurotoxicity of chlorpyrifos, malathion, and diazinon, while these effects were not detected in malaoxon and diazoxon. Taken together, our study suggests that mitochondrial toxicity and metabolic effects of CPF, but not CPF-oxon, have a key role of CPF neurotoxicity in the low-dose, chronic exposure. Further mechanistic studies are needed to examine mitochondria as a common target for all OP pesticide parent compounds, since this has important implications on cumulative pesticide risk assessment.
Quantifying Cell-type-specific Differences of Single-cell Datasets using UMAP and SHAP
Authors: Lim Hong Seo , Qiu Peng
Published: July 2022

With the rapid advances in single-cell profiling technologies, larger-scale investigations that require comparisons of multiple single-cell datasets can lead to novel findings. Specifically, quantifying cell-type-specific responses to different conditions across single-cell datasets could be useful in understanding how the difference in conditions is induced at a cellular level. Here we present a computational pipeline that quantifies the cell-type-specific differences and identifies genes responsible for the differences. We quantify differences observed in a low-dimensional UMAP space as a proxy for the difference present in the high-dimensional space and use SHAP to quantify genes driving the differences. Here we applied our algorithm to the Iris flower dataset, scRNA-seq dataset, and mass cytometry dataset, and demonstrate that it can robustly quantify the cell-type-specific differences and it can also identify genes that are responsible for the differences.
Lower Risks of Incident Colorectal Cancer in SGLT2i Users Compared to DPP4i Users: A Propensity Score-matched Study with Competing Risk Analysis
Authors: Chiu Chan Raymond Ngai , Fung Chan Robert Ngai , In Chou Oscar Hou , Loy Lee Teddy Tai , Roever Leonardo , Li Guoliang , Wong Wing Tak , Chung Wai Abraham Ka , Liu Tong , Tse Gary , Lee Sharen
Published: July 2022

Background

Diabetes mellitus is associated with the development of colorectal cancer (CRC). There have been a lack of study comparing the risk of colorectal cancer in sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i), both of which commonly prescribed second line agents for diabetes.

Methods

We conducted a territory wide retrospective cohort study on patients with type 2 diabetes who was prescribed either of the two agents. Baseline demographics, use of other medications, comorbidities and biochemical parameters were extracted. Propensity score matching was performed to reduce the impacts of cofounders. Cause specific Cox regression was used to evaluate the risk of incident colorectal cancer in SGLT2i users, as compared to DPP4i users. Subgroup analyses based on age, gender and estimated glomerular filtration rate were performed.

Results

After propensity score matching, we included 13029 subjects who were prescribed SGLT2i and DPP4i respectively. Incidence rate ratio of CRC was 0.566 (0.418-0.766) in SGLT2i users. Overall, use of SGLT2i was associated with a lower risk of incident CRC (HR: 0.526; 95% CI: 0.382-0.724; P <0.001). In subgroup analyses, use of SGLT2i was associated with lower risks of incident CRC only in men (HR: 0.461; 95% CI: 0.303-0.702; P <0.001), patients < 65 years old and patients (HR:0.294; 95% CI: 0.174-0.496; P<0.001) with eGFR ≥ 45 mL/min/ 1.73m2(HR: 0.560; 95% CI: 0.395-0.792; P =0.001).

Conclusion

Use of SGLT2i may reduce risk of incident CRC as compared to use of DPP4i, especially in younger male patients with fairly preserved renal function.
High-Resolution Spatiotemporal Analysis of Single Serotonergic Axons in an In Vitro System
Authors: Hingorani Melissa , Viviani Adele M.L. , Sanfilippo Jenna E. , Janušonis Skirmantas
Published: July 2022

Vertebrate brains have a dual structure in that they are composed of (i) axons that can be well captured with graph-theoretical methods and (ii) axons that form a dense matrix in which neurons with precise connections operate. A core part of this matrix is formed by axons (fibers) that store and release 5-hydroxytryptamine (5-HT, serotonin), an ancient neurotransmitter that supports neuroplasticity and has profound implications for mental health. The self-organization of the serotonergic matrix is not well understood, despite recent advances in experimental and theoretical approaches. In particular, individual serotonergic axons produce highly stochastic trajectories, fundamental to the construction of regional fiber densities, but further advances in predictive computer simulations require more accurate experimental information. This study examined single serotonergic axons in culture systems (co-cultures and monolayers), by using a complementary set of high-resolution methods: confocal microscopy, holotomography (refractive index-based live imaging), and super-resolution (STED) microscopy. It shows that serotonergic axon walks in neural tissue may strongly reflect the stochastic geometry of this tissue and it also provides new insights into the morphology and branching properties of serotonergic axons. The proposed experimental platform can support next-generation analyses of the serotonergic matrix, including seamless integration with supercomputing approaches.
Dissecting the genetic basis of the heterosis of Y900, an elite super-hybrid rice
Authors: Sun Zhizhong , Peng Jianxiang , Lv Qiming , Ding Jia , Chen Siyang , Duan Meijuan , He Qiang , Wu Jun , Tian Yan , Yu Dong , Tan Yanning , Sheng Xiabing , Chen Jin , Sun Xuewu , Liu Ling , Peng Rui , Liu Hai , Zhou Tianshun , Xu Na , Yuan Longping , Wang Bingbing , Yuan Dingyang
Published: July 2022

Y900 is one of the top hybrid rice varieties with a yield exceeding 15 t/hm2. To dissect the mechanism of heterosis, the male parent line R900 and female parent line Y58S were sequenced using long-read and Hi-C technology. High-quality reference genomes of sizes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 SNPs and 299,149 Indels. No megabase level structural variations exist. >75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the Geng/japonica-type genetic components from different male parents showed an increasing trend from phase 2-4 super-hybrid rice; Transcriptome analysis revealed that additive and dominance effects are the main genetic effects that constitute the heterosis of Y900. Allele-specific expression patterns and expression regulation patterns are quite dynamic in different tissues. For young panicle tissues, cis-regulation is dominant, while trans-regulation is more popular in leaf issues. Overdominance is more likely regulated by the trans-regulation mechanism. The differential gene expression and regulation pattern are closely related to Geng/japonica introgression. Additionally, R900 contained several excellent japonica haplotypes, such as NAL1, OsSPL13, Ghd8, OsBRI1, and DTH2, which make a good complement to Y58S. The fine tune mechanism through dynamic expression or regulation pattern change, especially on some key functional genes, is the base for heterosis.
Exploring Differential Gene Expression Profiles OfDero (Allodero) HylaeIn Their Parasitic And Free-Living Forms
Authors: Bonham Claire , Roguski Ashley , Langford Gabriel , Macrander Jason
Published: July 2022

Parasitism is ubiquitous in nature, yet little is known about the evolutionary mechanisms that lead to a parasitic lifestyle. Facultative parasites can switch between free-living and parasitic lifestyles, which may provide an opportunity to study the genetic mechanisms underlying a transition to parasitism. The oligochaeteDero (Allodero) hylaeis a facultative parasite commonly found within the ureter of various anuran species, such as the Cuban Tree Frog (Osteopilus septentrionalis).Dero hylaemakes passage through the frog’s cloaca, where it then infects the ureter. In the ureter, the worm loses free-living characteristics such as hair setae, dorsal setae, a digestive tract, and fossa with gills as it transitions to a parasitic lifestyle.Dero hylaemay be expelled from its host during urination, when this occurs the worm will reacquire free-living characteristics. The focus of this study is to compare the differential gene expression profiles observed when this rapid morphological change takes place. Specimens ofD. hylaewere collected from wild Cuban Tree Frogs and either flash-frozen for their parasitic stage RNA profile or cultured for two weeks to produce their free-living stage and then flash-frozen. Using the sequenced RNA, ade novotranscriptome was assembled and differential gene expression RNA Tag-Seq analysis between the free-living and parasitic life forms was analyzed. Based on these results, we have identified 213 genes differentially expressed transcripts between the two life forms, 190 of these being up-regulated in the free-living life form. While over half of the differential genes recovered did not recover any significant BLAST hits, many of these genes did provide insight into which molecular signals are potentially used byD. hylaeto lose and subsequently regrow their setae, digestive tract, and gills. This analysis provides significant insight into which differentially expressed genes are linked to drastic morphological changes observed in this rare oligochaete parasitism across the free-living and parasitic forms ofD. hylae.
Systematic comparison and rational design of theophylline riboswitches for efficient gene repression
Authors: Wang Xun , Fang Can , Wang Yifei , Shi Xinyu , Yu Fan , Xiong Jin , Chou Shan-Ho , He Jin
Published: July 2022

Riboswitches are promising regulatory tools in synthetic biology. To date, 25 theophylline riboswitches have been developed for gene expression regulation in bacteria. However, no one has systematically evaluated their regulatory effects. To facilitate rational selection of theophylline riboswitches, we examined 25 theophylline riboswitches in Escherichia coli and surprised to find that none of the five repressive riboswitches were more than 2-fold effective. To solve this problem, we rationally designed a transcriptional repressive riboswitch and demonstrated its effect not only in various bacterial strains but also in different growth media or different temperatures. By introducing two copies of theophylline riboswitches and a RepA protein degradation tag coding sequence at the 5’-end of a reporter gene, we successfully constructed a dual gene expression regulatory system with up to 150-fold potency, namely the R2-RepA system. R2-RepA system is only 218 bp in length, expression of any protein could be repressed efficiently by simply inserting this system upstream of the target protein-coding sequence. This study represented a crucial step toward harnessing theophylline riboswitches and expanding the synthetic biology toolbox.
Meta-analysis of fecal metagenomes reveals global viral signatures and its diagnostic potential for colorectal cancer and adenoma
Authors: Chen Fang , Li Shenghui , Guo Ruochun , Song Fanghua , Zhang Yue , Wang Xifan , Huo Xiaokui , Lv Qingbo , Ullah Hayan , Wang Guangyang , Ma Yufang , Yan Qiulong , Ma Xiaochi
Published: July 2022

Introduction

Gut microbiome plays an important role in maintaining human health. Although mounting evidence has revealed the critical function of the gut bacteriome in the progression of CRC, the contribution of gut viral community to CRC is rarely studied.

Objectives

The present study aimed to reveal the gut virome signatures of colorectal adenoma patients and CRC patients and decipher the potential viral markers to build clinical predictive models for diagnosis.

Methods

1,282 available fecal metagenomes data from 9 published CRC studies were collected. A new virus database was constructed based on a reference-independent virome approach for further analysis. Viral markers were filtered by statistical methods and used to build machine learning models such as Random Forest and Least Absolute Shrinkage and Selection Operator (LASSO) to distinguish patients from controls. New fecal samples were collected to validate the generalization of predictive model.

Results

The gut viral composition of CRC patients was drastically altered compared with healthy, as evidenced by changes in several Siphoviridae viruses and a reduction of Microviridae, whereas the virome variation in adenoma patients was relatively low. The viral markers contained the phages of Porphyromonas, Fusobacterium, Hungatella, and Ruminococcaceae. In 9 cohorts and independent validation cohorts, a random forest (RF) classifier and LASSO model got the optimal AUC 0.830 and 0.906, respectively. While the gut virome analysis of adenoma patients identified 88 differential viruses and achieved an optimal AUC of 0.772 for discriminating patients from controls.

Conclusion

Our findings demonstrate the distinctly different composition of gut virome between healthy controls and CRC patients, and highlight the potential of viral markers for clinical diagnosis.
Exploring Impacts to COVID-19 Herd Immunity Thresholds Under Demographic Heterogeneity that Lowers Vaccine Effectiveness
Authors: Paris Chloé Flore , Spencer Julie Allison , Castro Lauren A. , Del Valle Sara Y.
Published: July 2022

The COVID-19 pandemic has caused severe health, economic, and societal impacts across the globe. Although highly efficacious vaccines were developed at an unprecedented rate, the heterogeneity in vaccinated populations has reduced the ability to achieve herd immunity. Specifically, as of Spring 2022, the 0–4 year-old population is still unable to be vaccinated and vaccination rates across 5-11 year olds are low. Additionally, vaccine hesitancy for older populations has further stalled efforts to reach herd immunity thresholds. This heterogeneous vaccine landscape increases the challenge of anticipating disease spread in a population. We developed an age-structured Susceptible-Infectious-Recovered-type mathematical model to investigate the impacts of unvaccinated subpopulations on herd immunity. The model considers two types of undervaccination - age-related and behavior-related - by incorporating four age groups based on available FDA-approved vaccines. The model accounts for two different types of vaccines, mRNA (e.g., Pfizer, Moderna) and vector (e.g., Johnson and Johnson), as well as their effectiveness. Our goal is to analyze different scenarios to quantify which subpopulations and vaccine characteristics (e.g., rate or efficacy) most impact infection levels in the United States, using the state of New Mexico as an example.
Real-space texture and pole-figure analysis using the 3D pair distribution function on a platinum thin film
Authors: Harouna-Mayer Sani Y. , Tao Songsheng , Gong ZiZhou , v. Zimmermann Martin , Koziej Dorota , Dippel Ann-Christin , Billinge Simon J. L.
Published: July 2022

An approach is described for studying texture in nanostructured materials. The approach implements the real-space texture pair distribution function (PDF), txPDF, laid out by Gong & Billinge {(2018). arXiv:1805.10342 [cond-mat]}. It is demonstrated on a fiber-textured polycrystalline Pt thin film. The approach uses 3D PDF methods to reconstruct the orientation distribution function of the powder crystallites from a set of diffraction patterns, taken at different tilt angles of the substrate with respect to the incident beam, directly from the 3D PDF of the sample. A real-space equivalent of the reciprocal-space pole figure is defined in terms of interatomic vectors in the PDF and computed for various interatomic vectors in the Pt film. Furthermore, it is shown how a valid isotropic PDF may be obtained from a weighted average over the tilt series, including the measurement conditions for the best approximant to the isotropic PDF from a single exposure, which for the case of the fiber-textured film was in a nearly grazing incidence orientation of ∼10°. Finally, an open-source Python software package, FouriGUI, is described that may be used to help in studies of texture from 3D reciprocal-space data, and indeed for Fourier transforming and visualizing 3D PDF data in general.
Impacts of emotional regulation, adaptive selling and customer-oriented behavior on sales performance: the moderating role of job resourcefulness
Authors: Kuo Szu-Yu , Kao Ya-Ling , Tang Jia-Wei , Tsai Pei-Hsuan
Published: July 2022

Purpose

Given the increasing intensity of highly competitive markets, this study aims to evaluate the effect of salespeople's emotional regulation, adaptive selling and customer-oriented behavior on sales performance.

Design/methodology/approach

A research model was tested by using a sample of 288 respondents from the logistics industry in Taiwan. Structural equation modeling was used to examine the relationships between emotional regulation, adaptive selling, job resourcefulness, customer-oriented behavior and sales performance.

Findings

The results indicate that emotional regulation, adaptive selling and job resourcefulness can improve customer-oriented behavior, and that customer-oriented behavior and job resourcefulness can enhance sales performance. By highlighting the role of job resourcefulness, the authors find a positive moderating effect among these four dimensions.

Originality/value

The findings can help salespeople integrate customer-oriented behaviors into strategic changes to regulate their own emotions and those of others to productively address and resolve difficult business conditions. The theoretical and managerial implications of this work's contributions to international logistics are also discussed.