bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Surgeon Training Affect Patient Perception of Surgeon Skill in DIEP Flap Breast Reconstruction?
Authors: Bhat Deepa , Kollu Tejas , Giutashvili Tinatini , Patel Ashit , Ricci Joseph A.
Published: August 2021

Background The aim of this study is to investigate whether a surgeon's training background and years of experience advertised on a social media platform influences perception of surgeon competence, patient recruitment likelihood, and referral likelihood.

Methods A mockup of an Instagram post was created using a before and after picture of a deep inferior epigastric perforator (DIEP) flap patient. The caption under each post was changed to reflect one of six possible training categories: 1 year of experience, 10 years of experience, 20 years of experience, fellowship, Ivy League training, and a null case (with no training information against which all other cases were compared). Surveys asked female responders to evaluate surgeon competence, likelihood of becoming a patient, and likelihood of making a referral to their friends or family. Amazon MTurk crowdsourcing platform was used to distribute the survey.

Results A total of 1,878 responses were recorded, with the majority identifying as Caucasian (59%). The surgeon with 20 years of experience had the highest patient recruitment scores when compared with the null, 1 year, 10 year, and Ivy League training backgrounds (p = 0.0314, p = 0.0065, p = 0.0207, and p = 0.0244, respectively). The majority of responders (67%) preferred a female surgeon. Responders with a history of breast reconstruction assigned lower surgeon competence scores compared with women without a history of breast cancer (p <0.0001). Women who underwent breast reconstruction were also less likely to make referrals to their family and friends (p <0.0001).

Conclusion Surgeon's experience influences whether a patient is likely to seek care from a plastic surgeon. Personal history of breast cancer has a negative impact on perceived surgeon competence as well as patient recruitment likelihood and referral likelihood. Emphasizing fewer years of training or Ivy League training did not make an appreciable difference in patient perception of competence or likelihood of recruiting a new patient.
The Versatility of the DCIA Free Flap: A Forgotten Flap? Systematic Review and Meta-Analysis
Authors: Escandón Joseph M. , Bustos Valeria P. , Escandón Lauren , Santamaría Eric , Gaxiola-García Miguel A. , Kushida-Contreras Beatriz H. , Forte Antonio J. , Ciudad Pedro , Langstein Howard N. , Manrique Oscar J.
Published: August 2021

Background Studies reporting on the deep circumflex iliac artery (DCIA) free flap are restricted to a limited number of patients and areas of application. The aim of this review was to assess the reliability and versatility of the DCIA free flap during reconstruction.

Methods A comprehensive review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines using PubMed, Web of Science, Cochrane CENTRAL, and SCOPUS. A critical analysis of pooled data was performed to assess outcomes employing the DCIA free flap.

Results A total of 445 DCIA free flaps were included. The main recipient sites were head and neck (72.35%), lower extremity (20.67%), and upper extremity (6.74%). The main indications for reconstruction were tumor resection (73.8%) and trauma (17.43%). Fifty non-DCIA flaps were required to finalize the reconstruction of several defects. The pooled flap failure rate using the DCIA free flap was 4% (95% confidence interval: 1–8%). No significant heterogeneity was present across studies (Q statistic 22.12, p = 0.14; I 2 = 27.68%, p = 0.139). Complication rates for head and neck and limb reconstruction were 57.37 and 40.16%, respectively. The average length and surface area of bone flaps were 7.79 cm and 22.8 cm2, respectively. The area of the skin paddles was 117 cm2.

Conclusion The DCIA free flap has shown to be a versatile reconstructive alternative for head and neck and short-medium size limb defects. However, the complexity of functions, the recipient site location, and a potential large defect can detract from the use of the DCIA free flap as an initial reconstructive option for head and neck and extensive limb defects.
What does co-design mean for Australia’s diverse clinical workforce?
Authors: Harrison Reema , Chin Melvin , Ni She Eidin
Published: August 2021

Co-design is increasingly employed as a user-centric method to create healthcare change. In healthcare co-design, small groups of consumers and healthcare workers come together to identify processes, policies or service elements that require improvement and to design solutions. Multiple frameworks have emerged to guide the health work force and health researchers how to conduct co-design and support consumer members to engage in the process effectively. Frameworks have sought to address the propensity for co-design to exacerbate inequities for consumers with complex care needs or in under-served populations. Advice regarding the need to consider and ensure co-design is accessible to an increasingly diverse health workforce is, however, lacking. Drawing on our experience co-designing with diverse consumer and healthcare-worker populations, we discuss the implications of co-design for the healthcare workforce.
The use of Hereford sires over mature Angus dams can add value to Angus cattle herds
Authors: Pitchford J. M. , Jones J. , Hebart M. L. , Pitchford W. S.
Published: August 2021

Context Overseas studies have quantified production differences of Hereford × Angus compared with purebred Angus for a range of traits including growth, carcass and reproductive traits. Aim This study aims to provide a comparison of Hereford × Angus and purebred Angus under modern grazing conditions in southern Australia. Methods Thirty Hereford and 22 Angus sires were mated to 1100 Angus cows and heifers in a large commercial herd run on pasture at Musselroe Bay, Tasmania. Approximately 1650 calves were born. Steers were grown on pasture for an average of 23 months and then slaughtered. Results Hereford sired calves were heavier at birth (+8.8%) and weaning (+4.1%). Hereford-sired calves from heifers (but not from mature cows) had more assisted births (+8.2%) and more calf deaths (10.0% vs 5.1%). Hereford-sired steers had higher hot standard carcass weight (+4.1%) and eye-muscle area (+3.2%) but when hot standard carcass weight was fitted as a covariate, eye-muscle area was no longer significant. Carcass quality measures (AUSMEAT marbling –25.8%, Meat Standards Australia marbling –10.5%, Meat Standards Australia index –1.0%) were poorer for Hereford-sired steers and fat colour (+6.9%) was darker. Meat samples from Hereford-sired steers had significantly lower colour indicators (L and b). There was no difference in cooking loss and shear force, and intramuscular fat was lower (3.0% vs 4.1%). Conclusions Hereford × Angus calves were heavier at birth than were purebred Angus, but had more calving difficulty and deaths associated with heifer dams. Hereford × Angus carcasses were heavier but had lower indicators of quality than did purebred Angus. Implications As Hereford × Angus steers produced a 4.1% heavier carcass, pure Angus steers would need to attract a premium of at least 4.1% for the additional marbling to give more value. Hereford bulls could be mated to Angus cows and not Angus heifers to avoid calving difficulties. Alternatively, good calving Hereford bulls could be selected using estimated breeding values when mating to Angus heifers.
Exploring genomic approaches to fast-track genetic gains in breechstrike resistance in Merino sheep
Authors: Dominik S. , Reverter A. , Porto-Neto L. R. , Greeff J. C. , Smith J. L.
Published: August 2021

Context Breech flystrike is a costly trait to measure. Industry investment into genetic solutions for breech flystrike has resulted in the availability of estimated breeding values for indicator traits, such as breech wrinkle, breech cover and dag. However, selection is based on indicator traits rather than breech flystrike itself, and genetic gains could be enhanced through genomic selection approaches. Aim This study investigated whether genomic approaches based on major genes, such as marker-assisted selection, or genomic selection based on genomic breeding values, would be the most efficient application of genomic information to enhance genetic gains for breech flystrike resistance. Methods The analysis comprised 1535 sheep of the Merino Breeding for Breech Flystrike Resistance Resource flocks from New South Wales and Western Australia with high density genotypes (actual and imputed). A genome-wide association study was conducted on breech flystrike and its indicator traits, namely, breech wrinkle, dag and breech cover. The study also estimated genomic breeding values and their accuracy. Key results The SNP associations found in this study did not point to the existence of few genes with major effects on breech flystrike resistance or its indicator traits. Throughout the genome, associations of small effect were found, which enabled the estimation of genomic breeding values. However, these were of low accuracy, as expected for the size of the dataset. Conclusion Genomic prediction of breeding values for breech flystrike resistance is a feasible tool for applying genomic technology in the Merino industry. Implications A reference population of appropriate size needs to be established for this difficult-to-measure trait, and a dispersed reference population could be an effective option.
History of zoos and aquariums.
Authors: Rees Paul A.
Published: August 2021

This chapter contains questions on the history of zoos and aquariums along with the famous people and animals associated with them.
Aquariums and aquatic exhibits.
Authors: Rees Paul A.
Published: August 2021

This chapter contains questions on the design, construction and operation of aquariums and aquatic exhibits and the management of water quality.
Visitor studies, zoo education and zoo research.
Authors: Rees Paul A.
Published: August 2021

This chapter contains questions on the behaviour of visitors in zoos, and the role of zoos in education and research.
Nutrition and food presentation.
Authors: Rees Paul A.
Published: August 2021

This chapter contains questions on the food provided for animals in zoos and aquariums, its nutritional value and presentation, and the anatomy and physiology of digestive systems.
Change in Perceived Stress and Health Behaviors of Emerging Adults in the Midst of the COVID-19 Pandemic
Authors: LaCaille Lara J , Hooker Stephanie A , Marshall Elaine , LaCaille Rick A , Owens Rhea
Published: August 2021

Background

The COVID-19 pandemic has resulted in unprecedented disruptions, restrictions, and concerns about physical and mental health. Emerging adulthood, including the first year of college, is associated with declines in healthy eating and physical activity, as well as possible heightened distress. The impact of COVID-19 may exacerbate these concerns.

Purpose

The purpose of this study was to examine changes in health behaviors and perceived stress in emerging adults over the first year of college and to determine whether prepandemic health behaviors were protective for mental health and stress during the initial changes after the COVID-19 pandemic.

Methods

First-year college students (N = 234, 58.6% female) completed three surveys during their first year of school, the third being after the onset of COVID-19 and during a stay-at-home order. At Time 3, we also assessed symptoms of anxiety and depression.

Results

Using linear mixed modeling, sedentary time increased and physical activity decreased over time, but 20%–35% of students reported improvements in these behaviors. Dietary changes appeared mixed, with some improvements noted early during COVID-19. Perceived stress increased over time. Multiple regression indicated that of the health behaviors examined for protective effects on mental health and stress during the pandemic, only diet quality emerged as a significant predictor.

Conclusions

Although notable declines in some health habits were observed over time, including following COVID-19 disruptions, some students reported improved health behaviors. Efforts should be directed at identifying and intervening with students most at risk for poor functioning.
Is Three a Crowd? The Influence of Companions on a Patient’s Decision to Transition to a Biosimilar
Authors: Gasteiger Chiara , Groom Katie M , Lobo Maria , Scholz Urte , Dalbeth Nicola , Petrie Keith J
Published: August 2021

Background

Involving patients in treatment decisions is commonplace in healthcare, and patients are frequently accompanied by a companion (support person). Companions are often actively involved in medical consultations, yet their impact on decisions to change medications is unknown.

Purpose

This study examines the influence of companions on a patient’s decision to transition from their bio-originator therapy to a biosimilar.

Methods

A parallel, two-arm randomized controlled trial was conducted with 79 patients taking a bio-originator for rheumatic diseases who regularly attend clinic with a companion. Patients were randomized to receive an explanation about a hypothetical transition to a biosimilar alone or with their companion. Patients reported willingness to transition, risk perceptions, difficulty understanding, social support, and completed the Decisional Conflict Scale and Satisfaction with Decision Scale.

Results

Companions did not influence decisions to transition to biosimilars or cognitive and affective risk perceptions. Accompanied patients reported more difficulty understanding the explanation (p = .006, Cohen’s d = .64) but thought it was more important to receive information with companions (p = .023, Cohen’s d = −.52). Companions did not impact decision satisfaction or decisional conflict. Receiving emotional, but not practical support, was associated with less decisional conflict in accompanied patients (p = .038, r2 = 0.20).

Conclusions

The presence of companions does not seem to influence risk perceptions or decisions about transitioning to biosimilars. Companions, however, impact the patient’s reporting of their ability to understand treatment explanations. Providers should check understanding in all patients but may need to provide additional time or educational resources to accompanied patients and companions.

Trial registration

Australian New Zealand Clinical Trial Registry: ACTRN12619001435178.
Accelerated antibody discovery targeting the SARS-CoV-2 spike protein for COVID-19 therapeutic potential
Authors: Mullen Tracey E , Abdullah Rashed , Boucher Jacqueline , Brousseau Anna Susi , Dasuri Narayan K , Ditto Noah T , Doucette Andrew M , Emery Chloe , Gabriel Justin , Greamo Brendan , Patil Ketan S , Rothenberger Kelly , Stolte Justin , Souders Colby A
Published: August 2021

Background

Rapid deployment of technologies capable of high-throughput and high-resolution screening is imperative for timely response to viral outbreaks. Risk mitigation in the form of leveraging multiple advanced technologies further increases the likelihood of identifying efficacious treatments in aggressive timelines.

Methods

In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the severe acute respiratory syndrome coronavirus-2 spike protein. Working with human transgenic Alloy-GK mice, we detail a single B-cell discovery workflow to directly interrogate antibodies secreted from plasma cells for binding specificity and ACE2 receptor blocking activity. Additionally, we describe a concurrent accelerated hybridoma-based workflow utilizing a DiversimAb™ mouse model for increased diversity.

Results

The panel of antibodies isolated from both workflows revealed binding to distinct epitopes with both blocking and non-blocking profiles. Sequence analysis of the resulting lead candidates uncovered additional diversity with the opportunity for straightforward engineering and affinity maturation.

Conclusions

By combining in vivo models with advanced integration of screening and selection platforms, lead antibody candidates can be sequenced and fully characterized within one to three months.
Amplification of Bias Due to Exposure Measurement Error
Authors: Richardson David B , Keil Alexander P , Cole Stephen R
Published: August 2021

Observational epidemiologic studies typically face challenges of exposure measurement error and confounding. Consider an observational study of the association between a continuous exposure and an outcome, where the exposure variable of primary interest suffers from classical measurement error (i.e., the measured exposures are distributed around the true exposure with independent error). In the absence of exposure measurement error, it is widely recognized that one should control for confounders of the association of interest to obtain an unbiased estimate of the effect of that exposure on the outcome of interest. However, here we show that, in the presence of classical exposure measurement error, the net bias in an estimate of the association of interest may increase upon adjustment for confounders. We offer an analytical expression for calculating the change in net bias in an estimate of the association of interest upon adjustment for a confounder in the presence of classical exposure measurement error, and we illustrate this problem using simulations.
The link between brain acidosis, breathing and seizures: a novel mechanism of action for the ketogenic diet in a model of infantile spasms
Authors: Choudhary Anamika , Mu Chunlong , Barrett Karlene T , Charkhand Behshad , Williams-Dyjur Christine , Marks Wendie N , Shearer Jane , Rho Jong M , Scantlebury Morris H
Published: August 2021

Infantile spasms (IS) syndrome is a catastrophic, epileptic encephalopathy of infancy that is often refractory to current antiepileptic therapies. The ketogenic diet (KD) has emerged as an alternative treatment for patients with medically intractable epilepsy, though the prospective validity and mechanism of action for IS remains largely unexplored. We investigated the KD’s efficacy as well as its mechanism of action in a rodent model of intractable IS. The spasms were induced using the triple-hit paradigm and the animals were then artificially reared and put on either the KD (4:1 fats: carbohydrate + protein) or a control milk diet (CM; 1.7:1). 31Phosphorus magnetic resonance spectroscopy (31P MRS) and head-out plethysmography were examined in conjunction with continuous video-EEG behavioural recordings in lesioned animals and sham-operated controls. The KD resulted in a peripheral ketosis observed both in the blood and urine. The KD led to a robust reduction in the frequency of spasms observed, with approximately a 1.5-fold increase in the rate of survival. Intriguingly, the KD resulted in an intracerebral acidosis as measured with 31P MRS. In addition, the respiratory profile of the lesioned rats on the KD was significantly altered with slower, deeper and longer breathing, resulting in decreased levels of expired CO2. Sodium bicarbonate supplementation, acting as a pH buffer, partially reversed the KD’s protective effects on spasm frequency. There were no differences in the mitochondrial respiratory profiles in the liver and brain frontal cortex measured between the groups, supporting the notion that the effects of the KD on breathing are not entirely due to changes in intermediary metabolism. Together, our results indicate that the KD produces its anticonvulsant effects through changes in respiration leading to intracerebral acidosis. These findings provide a novel understanding of the mechanisms underlying the anti-seizure effects of the KD in IS. Further research is required to determine whether the effects of the KD on breathing and intracerebral acid-base balance are seen in other paediatric models of epilepsy.
Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Series From a 12-Month Longitudinal Occupational Cohort
Authors: Mack Christina D , Tai Caroline , Sikka Robby , Grad Yonatan H , Maragakis Lisa L , Grubaugh Nathan D , Anderson Deverick J , Ho David , Merson Michael , Samant Radhika M , Fauver Joseph R , Barrett James , Sims Leroy , DiFiori John
Published: August 2021

Findings are described in 7 patients with severe acute respiratory syndrome coronavirus 2 reinfection from the National Basketball Association 2020–2021 occupational testing cohort, including clinical details, antibody test results, genomic sequencing, and longitudinal reverse-transcription polymerase chain reaction results. Reinfections were infrequent and varied in clinical presentation, viral dynamics, and immune response.
UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons
Authors: Kulkarni Sucheta S , Sabharwal Vidur , Sheoran Seema , Basu Atrayee , Matsumoto Kunihiro , Hisamoto Naoki , Ghosh-Roy Anindya , Koushika Sandhya P
Published: August 2021

Neuronal regeneration after injury depends on the intrinsic growth potential of neurons. Our study shows that UNC-16, a Caenorhabditis elegans JIP3 homolog, inhibits axonal regeneration by regulating initiation and rate of regrowth. This occurs through the inhibition of the regeneration-promoting activity of the long isoform of DLK-1 and independently of the inhibitory short isoform of DLK-1. We show that UNC-16 promotes DLK-1 punctate localization in a concentration-dependent manner limiting the availability of the long isoform of DLK-1 at the cut site, minutes after injury. UNC-16 negatively regulates actin dynamics through DLK-1 and microtubule dynamics partially via DLK-1. We show that post-injury cytoskeletal dynamics in unc-16 mutants are also partially dependent on CEBP-1. The faster regeneration seen in unc-16 mutants does not lead to functional recovery. Our data suggest that the inhibitory control by UNC-16 and the short isoform of DLK-1 balances the intrinsic growth-promoting function of the long isoform of DLK-1 in vivo. We propose a model where UNC-16’s inhibitory role in regeneration occurs through both a tight temporal and spatial control of DLK-1 and cytoskeletal dynamics.
Clonal evolution in serially passaged Cryptococcus neoformans × deneoformans hybrids reveals a heterogenous landscape of genomic change
Authors: Michelotti Lucas A , Sun Sheng , Heitman Joseph , James Timothy Y
Published: August 2021

Cryptococcus neoformans × deneoformans hybrids (also known as serotype AD hybrids) are basidiomycete yeasts that are common in a clinical setting. Like many hybrids, the AD hybrids are largely locked at the F1 stage and are mostly unable to undergo normal meiotic reproduction. However, these F1 hybrids, which display a high (∼10%) sequence divergence are known to genetically diversify through mitotic recombination and aneuploidy, and this diversification may be adaptive. In this study, we evolved a single AD hybrid genotype in six diverse environments by serial passaging and then used genome resequencing of evolved clones to determine evolutionary mechanisms of adaptation. The evolved clones generally increased fitness after passaging, accompanied by an average of 3.3 point mutations, 2.9 loss of heterozygosity (LOH) events, and 0.7 trisomic chromosomes per clone. LOH occurred through nondisjunction of chromosomes, crossing over consistent with break-induced replication, and gene conversion, in that order of prevalence. The breakpoints of these recombination events were significantly associated with regions of the genome with lower sequence divergence between the parents and clustered in sub-telomeric regions, notably in regions that had undergone introgression between the two parental species. Parallel evolution was observed, particularly through repeated homozygosity via nondisjunction, yet there was little evidence of environment-specific parallel change for either LOH, aneuploidy, or mutations. These data show that AD hybrids have both a remarkable genomic plasticity and yet are challenged in the ability to recombine through sequence divergence and chromosomal rearrangements, a scenario likely limiting the precision of adaptive evolution to novel environments.
Lifecourse Educational Trajectories and Hypertension in Midlife: An Application of Sequence Analysis
Authors: Duarte Catherine dP , Wannier S Rae , Cohen Alison K , Glymour M Maria , Ream Robert K , Yen Irene H , Vable Anusha M
Published: August 2021

Background

Higher educational attainment predicts lower hypertension. Yet, associations between nontraditional educational trajectories (eg, interrupted degree programs) and hypertension are less well understood, particularly among structurally marginalized groups who are more likely to experience these non-traditional trajectories.

Methods

In National Longitudinal Survey of Youth 1979 cohort data (N = 6 317), we used sequence and cluster analyses to identify groups of similar educational sequences—characterized by timing and type of terminal credential—that participants followed from age 14–48 years. Using logistic regression, we estimated associations between the resulting 10 educational sequences and hypertension at age 50. We evaluated effect modification by individual-level indicators of structural marginalization (race, gender, race and gender, and childhood socioeconomic status [cSES]).

Results

Compared to terminal high school (HS) diploma completed at traditional age, terminal GED (OR: 1.32; 95%CI: 1.04, 1.66) or Associate degree after <HS (OR: 1.93; 95%CI: 1.11, 3.35) was associated with higher hypertension. There was some evidence of effect modification. Hypertension associated with delayed HS diploma versus HS diploma at a traditional age (the reference) was lower for Black men than White men (interaction term: 0.44; 95%CI: 0.21, 0.91); similarly, hypertension associated with <HS versus completing HS at a traditional age was lower for people with low cSES than people with high cSES (interaction term: 0.52; 95%CI: 0.30, 0.90).

Conclusions

Both type and timing to terminal credential matter for hypertension but effects may vary by experiences of structural marginalization. Documenting the nuanced ways in which complex educational trajectories are associated with health could elucidate underlying mechanisms and inform systems-level interventions for health equity.
Importance of fracture deformation throughout hydraulic testing under in situ conditions
Authors: Schmidt P , Dutler N , Steeb H
Published: August 2021

In this work, we propose a hydro-mechanical simulation model to study the strong interaction of fluid flow and fracture deformation under in situ stress conditions. The general model is reduced under physics-based assumptions to provide an efficient numerical approach for inverse analysis of experimental studies and is applied to experimental field data obtained from hydraulic tests conducted at the Grimsel Test Site, Switzerland. The present set of hydro-mechanical measurement data provides not only valuable information about the transient pressure and flow evolution but also the transient change of fracture deformation. We aim to introduce a strongly coupled hydro-mechanical model to numerically characterize the fractured reservoir based on experimental data below the limit of hydraulically induced irreversible changes of the reservoir’s properties. Insights into the leading mechanisms of flow processes throughout hydraulic testing under in situ conditions are then gained by best numerical fits of the measurement data. Based on the experimental and numerical findings, this study emphasizes the importance of a consistent consideration of local and non-local fracture deformation throughout inverse analysis of hydraulic testing data to (a) better understand hydro-mechanical flow processes in fractured reservoirs and (b) increase the estimation quality of hydraulic properties of tested fractures.
Does continuation of antifibrotics before lung transplantation influence post-transplant outcomes in patients with idiopathic pulmonary fibrosis?
Authors: Zhu Michael Z L , Huang Joanna Yilin , Liu David Hongwei , Snell Gregory I
Published: August 2021

A best evidence topic was written according to a structured protocol. The question addressed was: ‘Does continuation of antifibrotics before lung transplantation (LTx) influence post-transplant outcomes in patients with idiopathic pulmonary fibrosis (IPF) with regard to mortality, bronchial anastomotic dehiscence, reoperation for bleeding and wound complications, primary graft dysfunction or longer-term survival and allograft rejection?’ A total of 261 articles were found using the reported search strategy, of which 7 represented the best evidence to answer the clinical question. Six out of 7 studies demonstrated equivalent post-transplant survival among IPF patients on antifibrotics before LTx compared with controls. Five out of 6 studies showed no increase in the risk of major bleeding, wound or bronchial anastomotic complications. One bi-institutional study found a higher incidence of early bronchial anastomotic dehiscence, but this difference was not statistically significant after longer term follow-up. In a study that only included IPF patients who underwent single LTx, a lower incidence of grade 3 primary graft dysfunction was reported in the antifibrotic group compared with controls. Overall, to date, only small (N < 40 in the antifibrotic group), non-risk-adjusted, retrospective observational studies have been published. Notwithstanding, the summation of available evidence suggests that, in IPF patients, continuation of antifibrotic therapy before LTx is likely safe, and the rates of perioperative bleeding, wound or bronchial anastomotic complications, as well as 30-day and 1-year survival, are similar to patients not on antifibrotics before LTx.
Modern History of Cholera Vaccines and the Pivotal Role of icddr,b
Authors: Holmgren Jan
Published: August 2021

The rapid spread of the seventh cholera pandemic over Asia in the 1960s led to several large field studies that revealed that the traditional injectable cholera vaccines had poor efficacy, which led the World Health Organization (WHO) in the 1970s to stop recommending cholera vaccination. At the same time, it stimulated research that has led to the development of the effective orally administered cholera vaccines (OCVs) that today are a cornerstone in WHO’s strategy for Ending Cholera—A Global Roadmap to 2030. The first effective OCV, Dukoral, containing a mixture of inactivated Vibrio cholerae bacteria and cholera toxin B subunit, was licensed in 1991 and is, together with 2 similar inactivated whole-cell OCVs, Shanchol and Euvichol, currently WHO prequalified and recommended OCVs. This brief review is a personal account of the modern history of the development of these now universally recognized effective tools.
Flowcytometric and ImageStream RNA-FISH Gene Expression, Quantification and Phenotypic Characterization of Blood Stages and Sporozoites From Human Malaria Species
Authors: Luiza-Batista Camilla , Nardella Flore , Thiberge Sabine , Serra-Hassoun Malika , Ferreira Marcelo U , Scherf Artur , Garcia Sylvie
Published: August 2021

We adapted the RNA FISH Stellaris method to specifically detect the expression of Plasmodium genes by flow cytometry and ImageStream (Flow-FISH). This new method accurately quantified the erythrocytic forms of (1) Plasmodium falciparum and Plasmodium vivax and (2) the sexual stages of P vivax from patient isolates. ImageStream analysis of liver stage sporozoites using a combination of surface circumsporozoite protein (CSP), deoxyribonucleic acid, and 18S RNA labeling proved that the new Flow-FISH is suitable for gene expression studies of transmission stages. This powerful multiparametric single-cell method offers a platform of choice for both applied and fundamental research on the biology of malaria parasites.
The immunological significance of tumor necrosis factor receptor-associated factors (TRAFs)
Authors: So Takanori
Published: August 2021

The tumor necrosis factor receptor (TNFR)-associated factor (TRAF) family of molecules are intracellular signaling adaptors and control diverse signaling pathways mediated not only by the TNFR superfamily and the Toll-like receptor/IL-1 receptor superfamily but also by unconventional cytokine receptors such as IL-6 and IL-17 receptors. There are seven family members, TRAF1 to TRAF7, in mammals. Exaggerated immune responses induced through TRAF signaling downstream of these receptors often lead to inflammatory and autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease, psoriasis and autoinflammatory syndromes, and thus those signals are major targets for therapeutic intervention. For this reason, it has been very important to understand signaling mechanisms regulated by TRAFs that greatly impact on life/death decisions and the activation, differentiation and survival of cells of the innate and adaptive immune systems. Accumulating evidence suggests that dysregulated cellular expression and/or signaling of TRAFs causes overproduction of pro-inflammatory cytokines, which facilitates aberrant activation of immune cells. In this review, I will explain the structural and functional aspects that are responsible for the cellular activity and disease outcomes of TRAFs, and summarize the findings of recent studies on TRAFs in terms of how individual TRAF family molecules regulate biological and disease processes in the body in both positive and negative ways. This review also discusses how TRAF mutations contribute to human disease.
STAT5 interferes with PD-1 transcriptional activation and affects CD8+ T-cell sensitivity to PD-1-dependent immunoregulation
Authors: Wang Guanning , Tajima Masaki , Honjo Tasuku , Ohta Akio
Published: August 2021

Programmed cell death-1 (PD-1) is a co-inhibitory receptor that dampens immune responses upon interaction with PD-L1 and PD-L2. Although PD-1 expression on T cells is known to be activation-dependent, how cytokines modify its regulation is not fully resolved. Using polyclonal T-cell activation to study cytokine-dependent PD-1 regulation, we found that IL-2 inhibited transcriptional up-regulation of PD-1 despite the promotion of T-cell activation. The IL-2-mediated reduction in PD-1 expression augmented CD8+ T-cell activities against PD-L1-expressing target cells. To study the mechanism of PD-1 reduction, we focused on STAT5 activation in the IL-2 signaling pathway. Bioinformatic analysis suggested a novel conserved PD-1 promoter domain where NFAT and STAT5 can potentially compete with each other for binding. NFAT1 interaction with this domain revealed substantial potency in PD-1 transcription compared to STAT5A, and STAT5A overexpression could quench NFAT1-dependent PD-1 up-regulation in a sequence-specific manner. Chromatin immunoprecipitation analysis of activated T cells showed that IL-2 treatment significantly diminished the binding of NFAT1 and NFAT2 in the hypothesized competition site, while STAT5 binding to the same region was increased. These results raise the possibility that the competition of transcriptional factors might be involved in the fine-tuning of PD-1 expression by cytokines such as IL-2.
Using a new three-dimensional CUBIC tissue-clearing method to examine the brain during experimental cerebral malaria
Authors: Matsuo-Dapaah Julia , Lee Michelle Sue Jann , Ishii Ken J , Tainaka Kazuki , Coban Cevayir
Published: August 2021

Cerebral malaria (CM) is a life-threatening complication of the malaria disease caused by Plasmodium falciparum infection and is responsible for the death of half a million people annually. The molecular pathogenesis underlying CM in humans is not completely understood, although sequestration of infected erythrocytes in cerebral microvessels is thought to play a major role. In contrast, experimental cerebral malaria (ECM) models in mice have been thought to be distinct from human CM, and are mainly caused by inflammatory mediators. Here, to understand the spatial distribution and the potential sequestration of parasites in the whole-brain microvessels during a mouse model of ECM, we utilized the new tissue-clearing method CUBIC (Clear, Unobstructed, Brain/Body Imaging Cocktails and Computational analysis) with light-sheet fluorescent microscopy (LSFM), and reconstructed images in three dimensions (3D). We demonstrated significantly greater accumulation of Plasmodium berghei ANKA (PbANKA) parasites in the olfactory bulb (OB) of mice, compared with the other parts of the brain, including the cerebral cortex, cerebellum and brainstem. Furthermore, we show that PbANKA parasites preferentially accumulate in the brainstem when the OB is surgically removed. This study therefore not only highlights a successful application of CUBIC tissue-clearing technology to visualize the whole brain and its microvessels during ECM, but it also shows CUBIC’s future potential for visualizing pathological events in the whole ECM brain at the cellular level, an achievement that would greatly advance our understanding of human cerebral malaria.
Rapid evaluation of the substrate specificity of 3-nitrobenzoic acid dioxygenase MnbAB via colorimetric detection using Saltzman reagent
Authors: Tomita Hiroya , Katsuyama Yohei , Ohnishi Yasuo
Published: August 2021

Nitroaromatic compounds are essential materials for chemical industry, but they are also potentially toxic environmental pollutants. Therefore, their sensitive detection and degradation are important concerns. The microbial degradation pathways of nitroaromatic compounds have been studied in detail, but their usefulness needs to be evaluated to understand their potential applications in bioremediation. Here, we developed a rapid and relatively sensitive assay system to evaluate the activities and substrate specificities of nitroaromatic dioxygenases involved in the oxidative biodegradation of nitroaromatic compounds. In this system, nitrous acid, which was released from the nitroaromatic compounds by the dioxygenases, was detected and quantified using the Saltzman reagent. Escherichia coli producing the 3-nitrobenzoic acid dioxygenase complex MnbAB from Comamonas sp. JS46 clearly showed the apparent substrate specificity of MnbAB as follows. MnbAB accepted not only 3-nitrobenzoic acid but also several other p- and m-nitrobenzoic acid derivatives as substrates, although it much preferred 3-nitrobenzoic acid to others. Furthermore, the presence of a hydroxy or an amino group at the ortho position of the nitro group decreased the activity of MnbAB. In addition, MnbAB accepted 2-(4-nitrophenyl)acetic acid as a substrate, which has one additional methylene group between the aromatic ring and the carboxy group of 3-nitrobenzoic acid. This is the first report about the detailed substrate specificity of MnbAB. Our system can be used for other nitroaromatic dioxygenases and contribute to their characterization.
Underserved Pacific Islanders With Locally Advanced Cervical Cancer Receive Higher Rates of Standard-of-Care Radiation Treatment Through the Pacific Island Health Care Project and Military Health System Compared to the Average U.S. Population
Authors: Sitler Collin , Bunch Kristen P , Padro David , Miller Caela R
Published: August 2021

Introduction

Brachytherapy, with external beam radiation, increases survival in the treatment of locally advanced cervical cancer (LACC). In 2016, Robin et al. reported only 44% of patients received standard-of-care (SOC) brachytherapy in the USA. The Pacific Island Health Care Project has provided humanitarian medical care to women from the U.S. Associated Pacific Islands (USAPI) for three decades at Tripler Army Medical Center (TAMC), a military health care system (MHS) facility. We evaluated whether this underserved and understudied patient population received SOC treatment for LACC at TAMC.

Materials and Methods

The TAMC tumor registry was searched for all cervical cancer cases from 1997 to 2019. Subjects were excluded if they did not have stage IB2-IVA disease and were not from USAPI. The primary outcome was the overall utilization of brachytherapy, and statistical analysis was performed using the chi-square test.

Results

We identified 214 women with cervical cancer treated at TAMC, of which 67 met the study criteria. Ninety-two percent had squamous cell carcinoma on histology. Of the patients identified, 48 (71.6%, P < .001) were treated with brachytherapy. Fifteen (22.4%) patients received external radiation alone, and four (6.0%) received chemoradiation without brachytherapy. A post-hoc power analysis was conducted with a power of 91.3%.

Conclusions

Women with cervical cancer from USAPI in the PIHCP program treated at TAMC received significantly higher rates of SOC radiation treatment than the U.S. population on average. This highlights the ability of PIHCP, through the MHS, to deliver SOC treatment for cervical cancer to an otherwise underserved patient population.
The Relation of Surgical Volume to Competence: When Is Enough, Enough?
Authors: Carnduff Mary , Place Ronald
Published: August 2021

Given the inherent risk in surgical intervention and the need for the optimal utilization of health care resources, achieving high-quality surgical care is a priority for the American health care system, and competent surgeons are critical to reaching this goal. Despite the multifactorial nature of patient safety and satisfaction, surgeon competence is often oversimplified to an assessment of volume because of the ease of collection and comparison. In any practice model, the analysis of competence is complex, but the components of clinical skill for military surgeons further include multiple areas of expertise, which, although superficially unrelated to surgical currency, augment the overall care delivered by these clinicians. Thus, volume as a solitary indicator of skill excludes the unique circumstances encompassed in military service. In this paper, the factors comprising volume and competence are explained, as well as the additional factors unique to military medicine. Furthermore, process improvements are proposed for assessing and optimizing surgical competence in the Military Health System.
NuSTAR and Swift observations of the extragalactic black hole X-ray binaries
Authors: Jana Arghajit , Naik Sachindra , Chatterjee Debjit , Jaisawal Gaurava K
Published: August 2021

We present the results obtained from detailed spectral and timing studies of extragalactic black hole X-ray binaries LMC X–1 and LMC X–3, using simultaneous observations with Nuclear Spectroscopic Telescope Array (NuSTAR) and Neil Gehrels Swift observatories. The combined spectra in the 0.5–30 keV energy range, obtained between 2014 and 2019, are investigated for both sources. We do not find any noticeable variability in 0.5–30 keV light curves, with 0.1–10 Hz fractional rms estimated to be <2 per cent. No evidence of quasi-periodic oscillations is found in the power density spectra. The sources are found to be in the high soft state during the observations with disc temperature Tin ∼ 1 keV, photon index, Γ > 2.5 and thermal emission fraction, fdisc > 80 per cent. An Fe Kα emission line is detected in the spectra of LMC X–1, though no such feature is observed in the spectra of LMC X–3. From the spectral modelling, the spins of the black holes in LMC X–1 and LMC X–3 are estimated to be in the range of 0.92–0.95 and 0.19−0.29, respectively. The accretion efficiency is found to be, η ∼ 0.13 and η ∼ 0.04 for LMC X–1 and LMC X–3, respectively.
Efficacy of romosozumab for osteoporosis in a patient with osteogenesis imperfecta: A case report
Authors: Uehara Masashi , Nakamura Yukio , Nakano Masaki , Miyazaki Akiko , Suzuki Takako , Takahashi Jun
Published: August 2021

The efficacy of romosozumab for severe osteoporosis is uncertain in patients with osteogenesis imperfecta (OI). This report introduced a severe osteoporotic case of OI to examine the effect of romosozumab on bone fragility. A 64-year-old man with OI was referred to our department for finding out the cause of his repeated fractures. He was medicated with alendronate for only 1 year, 8 years ago, but it did not prevent repeated fractures, and thus, he had not received any treatments for osteoporosis since then. However, recently, the frequency of fractures had increased. At presentation, his lumbar and bilateral total hip bone mineral density (BMD) values were severely decreased to 0.546 and 0.209 g/cm2, respectively. Because of his severe osteoporosis, we started romosozumab treatment with eldecalcitol. Romosozumab (210 mg) was injected subcutaneously every month. At 12 months after drug initiation, his lumbar and total hip BMD increased by 22.0% and 136.4% versus pre-treatment levels, respectively. Bone formation markers increased, and bone resorption markers decreased at 12 months of the therapy. Neither hypocalcaemia nor any other severe adverse effects were observed in this severe osteoporotic case. This study revealed good responses of BMD and bone turnover markers to romosozumab treatment, which can be considered as an effective treatment option for osteoporotic OI patients.
Neurosarcoidosis pathologically diagnosed via biopsy of a normal-sized inguinal lymph node with fluorodeoxyglucose accumulation on positron emission tomography/computed tomography in a patient with a history of brain Ewing’s sarcoma
Authors: Fuwa Masayuki , Tateyama Shodai , Kato Ayaka , Asano Motochika , Taguchi Koichiro , Mori Ichiro , Ikeda Takahide , Kanayama Tomohiro , Shizui Natsuko , Morita Hiroyuki
Published: August 2021

Neurosarcoidosis is a rare disease and is often difficult to diagnose. Herein, we report a case of neurosarcoidosis in a patient with a history of Ewing’s sarcoma of the brain. He presented with fever of unknown origin, and a pathological diagnosis was obtained via biopsy of a normal-sized inguinal lymph node with fluorodeoxyglucose (FDG) accumulation on positron emission tomography/computed tomography (PET/CT). The condition could not have been diagnosed without FDG-PET/CT.
Aspergillus lentulus: An Under-recognized Cause of Antifungal Drug-Resistant Aspergillosis
Authors: Nematollahi Saman , Permpalung Nitipong , Zhang Sean X , Morales Megan , Marr Kieren A
Published: August 2021

Aspergillus lentulus is a drug-resistant species that is phenotypically similar to A. fumigatus. It was discovered as a cause of azole-breakthrough disease, consistent with in vitro resistance. Clinical labs can misidentify the species as fumigatus based on phenotypic typing. We describe 4 recent cases and provide a brief review.