bluuebunny/crossref_metadata_2025 huggingface dataset:
SPiRaL: a multiresolution global tomography model of seismic wave speeds and radial anisotropy variations in the crust and mantle
Authors: Simmons N A , Myers S C , Morency C , Chiang A , Knapp D R
Published: July 2021

SPiRaL is a joint global-scale model of wave speeds (P and S) and anisotropy (vertical transverse isotropy, VTI) variations in the crust and mantle. The model is comprised of >2.1 million nodes with five parameters at each node that capture velocity variations for P- and S-waves travelling at arbitrary directions in transversely isotropic media with a vertical symmetry axis (VTI). The crust (including ice, water, sediments and crystalline layers) is directly incorporated into the model. The default node spacing is approximately 2° in the lower mantle and 1° in the crust and upper mantle. The grid is refined with ∼0.25° minimum node spacing in highly sampled regions of the crust and upper mantle throughout North America and Eurasia. The data considered in the construction of SPiRaL includes millions of body wave traveltimes (crustal, regional and teleseismic phases with multiples) and surface wave (Rayleigh and Love) dispersion. A multiresolution inversion approach is employed to capture long-wavelength heterogeneities commonly depicted in global-scale tomography images as well as more localized details that are typically resolved in more focused regional-scale studies. Our previous work has demonstrated that such global-scale models with regional-scale detail can accurately predict both teleseismic and regional body wave traveltimes, which is necessary for more accurate location of small seismic events that may have limited signal at teleseismic distances. SPiRaL was constructed to predict traveltimes for event location and long-period waveform dispersion for seismic source inversion applications in regions without sufficiently tuned models. SPiRaL may also serve as a starting model for full-waveform inversion (FWI) with the goal of fitting waves with periods 10–50 s over multiple broad regions (thousands of kilometres) and potentially the globe. To gain insight to this possibility, we simulated waveforms for a small set of events using SPiRaL and independent waveform-based models for comparison. For the events tested, the performance of the traveltime-based SPiRaL model is shown to be generally on par with regional 3-D waveform-based models in three regions (western United States, Middle East, Korean Peninsula) suggesting SPiRaL may serve as a starting model for FWI over broad regions.
Peripartum Exposure to Biologic Therapy Does Not Impact Postpartum Wound Healing in Women With IBD
Authors: Aboubakr Aiya , Gottlieb Zoë S , Riggs Alexa Rae , Johnson Shaelyn O’Hara , Jimenez Darwin , Rekawek Patricia , Mella Maria Teresa , Dubinsky Marla C
Published: July 2021

Background

Inflammatory bowel disease (IBD) commonly affects women during childbearing years and often requires antepartum therapy. Data regarding effects of biologic exposure on delivery outcomes are limited. We explored whether peripartum biologic exposure impacts wound healing following cesarean section (C-section) and vaginal delivery (VD) in IBD patients.

Methods

Pregnancy and IBD data from the IBD Preconception and Pregnancy Planning (I-PrePP) Clinic database were collected and analyzed. Primary outcome was frequency of postpartum wound infection in women receiving peripartum biologics, defined as exposure in the third trimester and up to 2 weeks postdelivery relative to nonexposed patients. Secondary outcomes included effect of peripartum biologic timing and IBD phenotype on wound healing. Descriptive statistics summarized data using frequency for categorical variables and median for continuous variables. Univariate analyses tested associations when appropriate.

Results

Of 100 deliveries (interquartile range, 30–35; median, 33 years old), 58 were C-sections and 42 VDs. Peripartum biologic exposure occurred in 72% (42 of 58) and 57% (24 of 42), respectively. Median time from last dose to delivery was 6 (interquartile range, 4–8) weeks; 21 (32%) received biologics within 72 hours following delivery. Seven infections occurred following C-section among 5 unique CD patients. Peripartum biologic exposure was not associated with infection (4 of 66 [6%] exposed vs 3 of 34 [8.8%] nonexposed; P = .68), nor was disease activity (P = 1.0). Crohn’s disease (P = 0.02), internal penetrating phenotype (P < .001), prior IBD surgery (P = .03), and prior postpartum infection (P = .04) were associated with infection.

Conclusions

Peripartum biologic exposure does not impair postpartum wound healing; however, patients with more complicated disease phenotypes require close monitoring.
IBD in the Postpartum Period: Spotlight on Maternal Outcomes
Authors: Bröms Gabriella
Published: July 2021

Lay Summary

With the peak incidence of IBD in the reproductive years, concerns related to pregnancy are frequently raised. This period is unique in that care involves more than one patient: the pregnant woman and her child/children. For long, focus has been primarily on infant outcomes. This study brings attention to maternal outcomes.
Barriers and Promises of the Developing Pigment Organelle Field
Authors: Figon Florent , Deravi Leila F , Casas Jérôme
Published: July 2021

Many colors and patterns in nature are regulated by the packaging and processing of intracellular pigment-containing organelles within cells. Spanning both molecular and tissue-level spatial scales with chemical and physical (structural) elements of coloration, pigment organelles represent an important but largely understudied feature of every biological system capable of coloration. Although vertebrate melanosomes have historically been the best-known and most studied pigment organelle, recent reports suggest a surge in studies focusing on other pigment organelles producing a variety of non-melanic pigments, optic crystals and structural colors through their geometric arrangement. In this issue, we showcase the importance of these integrative and comparative studies and discuss their results which aid in our understanding of organelle form and function in their native environment. Specifically, we highlight how pigment organelles can be studied at different scales of organization, across multiple species in biology, and with an interdisciplinary approach to better understand the biological and chemical mechanisms underlying color. This type of comparative approach provides evidence for a common origin and identity of membrane-bound pigment organelles not only in vertebrates, as was originally postulated 40 years ago, but in all animals. This indicates that we have much to gain by studying a variety of pigment organelles, as the specific biological context may provide important and unique insights into various aspects of its life. We conclude by highlighting some barriers to this research and discussing strategies to overcome them through a discussion of future directions for pigment organelle research.
Atrio-oesophageal fistula following atrial fibrillation ablation: how to manage this dreaded complication?
Authors: Moiroux-Sahraoui Alexander , Manceau Gilles , Schoell Thibaut , Combes Alain , Bouglé Adrien , Leprince Pascal , Vaillant Jean Christophe , Lebreton Guillaume
Published: July 2021

OBJECTIVES

Atrio-oesophageal fistula is a rare but serious complication of radiofrequency catheter ablation of atrial fibrillation. Therapeutic options are surgery, oesophageal stenting and conservative treatment (antibiotics and anticoagulation). However, there are no guidelines available. Since no article dwells on the technical considerations of this surgery, we aim to present here our experience and share our surgical approach.

METHODS

Between January 2012 and March 2020, all consecutive patients treated for atrio-oesophageal fistula following radiofrequency catheter ablation of atrial fibrillation at our institution were analysed retrospectively. The diagnosis was made on a set of clinical and radiological signs. All patients benefitted from a combined approach involving both digestive and cardiac surgeons. Femoro-femoral peripheral cardiopulmonary by-pass was used. The surgical approach was a right posterolateral thoracotomy. Atrial repair was done on fibrillating heart without cross-clamping, using a left atriotomy. Digestive management consisted of a total oesophagectomy.

RESULTS

We identified 6 patients with this complication. The median age was 53 [34–72] years. Symptoms were neurological symptoms, fever and chest pain. Diagnostic modalities were cerebral imaging, chest CT and transthoracic echocardiogram. Atrial repair consisted in a suture of the atrium or by using a pericardial patch. With a median follow-up of 3.1 [0.1–7.7] years, only one patient died during the follow-up.

CONCLUSIONS

Our experience shows that an aggressive surgery with a large resection of the oesophagus and left atrial repair by right thoracotomy in the same time provides good results. The ability to involve simultaneously both experienced digestive and cardiac surgical teams is the key for this strategy.
Stiffness reduction of the rib cage to perform a minimally invasive pectus excavatum repair: biomechanical evaluation
Authors: Vega-Artiles Ángel Gabriel , Pérez David , Martel Oscar , Cuadrado Alberto , Yánez Alejandro
Published: July 2021

OBJECTIVES

To study the influence of sternal transection and costal chondrotomies on the stiffness and stresses in the rib cage of adult patients undergoing Nuss pectus excavatum procedure.

METHODS

Four pectus excavatum models with different Haller indexes were created by parameterizing a 3D model of a rib cage obtained based on a computed tomography scan of a patient with no pectus deformity. Using the finite element method, insertion of intrathoracic bars into all models was simulated in 3 conditions, namely, non-intervened, transverse sternal section and costal chondrotomies. Stiffness, stress distribution and maximum stresses for each case were obtained and compared.

RESULTS

Transverse sternotomy provided a reduction of 44% to 54% in the stiffness of the rib cage, depending on the Haller index analysed, while chondrotomies promoted a stiffness reduction of 70%. Stress distribution in the rib cage followed similar pattern for all the tested Haller index, but the maximum stress decreased by 36% when performing a transverse sternotomy, whereas when performing costal chondrotomies, it decreased by 47%.

CONCLUSIONS

Computational results report that transverse sternotomy reduces appreciably the stiffness of the rib cage, while costal chondrotomies promote even a higher stiffness reduction. Thus, these surgical procedures could improve the clinical outcomes of adult patients undergoing a pectus excavatum repair.
Dictionaries in German and Spanish primary education curricula: A comparative study
Authors: Egido Vicente María
Published: July 2021

This paper presents the results of a comparative curriculum-based study conducted to analyse the way dictionaries and the development of lexicographical skills are addressed in primary education in Germany and Spain. To carry out the study, the curricula of two language subjects taught throughout the country were selected, namely First Language (German and Spanish, respectively) and First Foreign Language (English). Within the methodology framework for documentary analysis, several thematic categories will be identified inductively from explicit references located in the selected curricula that will serve as tertium comparationis. The main objective is to find out whether the curriculum regulations consider dictionaries and the development of specific skills for using them in this first stage of education as part of the process of training literacy in the first language and foreign language teaching-learning context.
Characterization of Boundedness on Weighted Modulation Spaces of τ-Wigner Distributions
Authors: Guo Weichao , Chen Jiecheng , Fan Dashan , Zhao Guoping
Published: July 2021

This paper is devoted to give several characterizations on a more general level for the boundedness of $\tau $-Wigner distributions acting from weighted modulation spaces to weighted modulation and Wiener amalgam spaces. As applications, sharp exponents are obtained for the boundedness of $\tau $-Wigner distributions on modulation spaces with power weights. We also recapture the main theorems of Wigner distribution obtained by Cordero and Nicola [10] and Cordero [6]. As consequences, the characterizations of the boundedness on weighted modulation spaces of several types of pseudodifferential operators are established. In particular, we give the sharp exponents for the boundedness of pseudodifferential operators with symbols in Sjöstrand’s class and the corresponding Wiener amalgam spaces.
Real-World Clinical Outcomes of Bamlanivimab and Casirivimab-Imdevimab Among High-Risk Patients With Mild to Moderate Coronavirus Disease 2019
Authors: Ganesh Ravindra , Philpot Lindsey M , Bierle Dennis M , Anderson Ryan J , Arndt Lori L , Arndt Richard F , Culbertson Tracy L , Destro Borgen Molly J , Hanson Sara N , Kennedy Brian D , Kottke Brian B , Larsen Jennifer J , Ramar Priya , Rosedahl Jordan K , Seville Maria Teresa , Speicher Leigh L , Tulledge-Scheitel Sidna M , Wilker Caroline G , Razonable Raymund R
Published: July 2021

Background

Bamlanivimab and casirivimab-imdevimab are authorized for treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk patients. We compared the outcomes of patients who received these therapies to identify factors associated with hospitalization and other clinical outcomes.

Methods

Adult patients who received monoclonal antibody from 19 November 2020 to 11 February 2021 were selected and divided into those who received bamlanivimab (n = 2747) and casirivimab-imdevimab (n = 849). The 28-day all-cause and COVID-19–related hospitalizations were compared between the groups.

Results

The population included 3596 patients; the median age was 62 years, and 50% were female. All had ≥1 medical comorbidity; 55% had multiple comorbidities. All-cause and COVID-19–related hospitalization rates at 28 days were 3.98% and 2.56%, respectively. After adjusting for medical comorbidities, there was no significant difference in all-cause and COVID-19–related hospitalization rates between bamlanivimab and casirivimab-imdevimab (adjusted hazard ratios [95% confidence interval], 1.4 [.9–2.2] and 1.6 [.8–2.7], respectively). Chronic kidney, respiratory and cardiovascular diseases, and immunocompromised status were associated with higher likelihood of hospitalization.

Conclusions

This observational study on the use of bamlanivimab and casirivimab-imdevimab in high-risk patients showed similarly low rates of hospitalization. The number and type of medical comorbidities are associated with hospitalizations after monoclonal antibody treatment.
Transcriptomic Analysis of Livers of Inactive Carriers of Hepatitis B Virus With Distinct Expression of Hepatitis B Surface Antigen
Authors: Rico Montanari Noe , Ramirez Ricardo , Van Buuren Nick , van den Bosch Thierry P P , Doukas Michail , Debes Jose D , Feierbach Becket , Boonstra Andre
Published: July 2021

Inactive carrier phases in chronic hepatitis B virus (HBV) infection present minimal liver disease and HBV replication activity suggesting partial immune reconstitution, although the mechanisms responsible remain elusive. Moreover, hepatitis B surface antigen (HBsAg) production—hypothesized to modulate the immune response—is unaltered. In the current study, we assessed the intrahepatic transcriptome in inactive carriers of HBV versus healthy liver donors, including in the context of diverse HBsAg levels (serum and liver), to better understand the phenomenon of immune control. We found a deregulated liver transcriptome in inactive carriers compared with healthy controls, despite normal liver function. Moreover, diverse HBsAg levels have minimal impact on the liver transcriptome in inactive carriers, although gene correlation analysis revealed that leukocyte activation, recruitment, and innate responses genes were correlated with liver HBsAg levels. These findings provide more insight into the mechanisms underlying anti-HBV strategies currently under development, aimed at interfering with HBsAg production or inducing a state of immune control.
Mechanisms for the regulation of memory B-cell recall responses in mice
Authors: Kitamura Daisuke
Published: July 2021

Upon infection by pathogens or vaccination, the adaptive immune system rapidly but transiently produces antibodies. Some weeks later, however, long-lasting immunity is established that protects the host against the same pathogens almost for life through continuous production of antibodies on one hand and the maintenance of cytotoxic T cells on the other, collectively called immunological memory. The antibody-mediated arm, also called serological memory, is mainly exerted by long-lived plasma cells and memory B cells (MBCs). MBCs express receptors for the specific pathogens and circulate to survey the body for almost a life-long period. Upon recognizing the pathogen, MBCs clonally expand and produce a large amount of the specific antibodies to stop the infection, the process called a (memory) recall response. Although such a function of MBCs has long been known, the mechanism of how their performance is regulated has been obscure. This is due to their paucity in the body, lack of definitive surface markers and obscure ontogeny. However, recent studies have revealed the multifold mechanisms by which the recall response of MBCs is regulated: rapid and enhanced antibody production is due to a mechanism intrinsic to MBCs, namely, up-regulated expression levels of surface molecules interacting with T cells and the property of IgG-class antigen receptors; to a property of the responsible subset of MBCs; and to co-stimulation through innate receptors and cytokines. It has also been unveiled that the recall response is negatively regulated by an inhibitory receptor on MBCs and by antigens with repetitive epitopes.
Comparison of 6 SARS-CoV-2 Molecular Methods and Correlation With the Cycle Threshold Distribution in Clinical Specimens
Authors: Raju Saravanan , Anderson Neil W , Robinson Elizabeth , Squires Crystal , Wallace Meghan A , Zhang Ray , Burnham Carey-Ann D , Parikh Bijal A
Published: July 2021

Background

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patient samples is of critical importance in the management of patients and monitoring transmission in the population. However, data on the analytical performance characteristics for detection of SARS-CoV-2 in clinical specimens between individual targets within the same platform, and among different analytical platforms, are limited.

Methods

Here we evaluated the performance of 6 different sample-to-answer SARS-CoV-2 detection methods—Roche cobas 6800, Cepheid GeneXpert, Diasorin Simplexa, Luminex Aries emergency use authorization (EUA), Luminex Aries research use only (RUO), and bioMérieux BioFire—in clinical specimens with a range of viral loads.

Results

The positive percentage agreement between the Roche cobas 6800 and GeneXpert was 100%, Diasorin 95%, Aries EUA 74%, Aries RUO 83%, and BioFire 97%. Notably, in samples with cycle threshold (Ct) values below 30 for the E gene on the Roche cobas 6800 platform, we found 100% positive agreement among all platforms. Given these results, we examined the distribution of over 10 000 Ct values of all positive specimens from individuals at our institution on the Roche cobas platform. Nearly 60% of specimens from asymptomatic individuals had a PCR Ct value >30 as measured using the cobas 6800 assay E gene.

Conclusions

Our results demonstrate performance characteristics between different platforms by Ct value and provide data regarding the distribution of viral RNA present in positive specimens.
New Insect Host Defense Peptides (HDP) From Dung Beetle (Coleoptera: Scarabaeidae) Transcriptomes
Authors: Téllez Ramirez Germán Alberto , Osorio-Méndez Juan Felipe , Henao Arias Diana Carolina , Toro S. Lily Johanna , Franco Castrillón Juliana , Rojas-Montoya Maribel , Castaño Osorio Jhon Carlos
Published: July 2021

The Coleoptera Scarabaeidae family is one of the most diverse groups of insects on the planet, which live in complex microbiological environments. Their immune systems have evolved diverse families of Host Defense Peptides (HDP) with strong antimicrobial and immunomodulatory activities. However, there are several peptide sequences that await discovery in this group of organisms. This would pave the way to identify molecules with promising therapeutic potential. This work retrieved two sources of information: 1) De-novo transcriptomic data from two species of neotropical Scarabaeidae (Dichotomius satanas and Ontophagus curvicornis); 2) Sequence data deposited in available databases. A Blast-based search was conducted against the transcriptomes with a subset of sequences representative of the HDP. This work reports 155 novel HDP sequences identified in nine transcriptomes from seven species of Coleoptera: D. satanas (n = 76; 49.03%), O. curvicornis (n = 23; 14.83%), (Trypoxylus dichotomus) (n = 18; 11.61%), (Onthophagus nigriventris) (n = 10; 6.45%), (Heterochelus sp) (n = 6; 3.87%), (Oxysternon conspicillatum) (n = 18; 11.61%), and (Popillia japonica) (n = 4; 2.58%). These sequences were identified based on similarity to known HDP insect families. New members of defensins (n = 58; 37.42%), cecropins (n = 18; 11.61%), attancins (n = 41; 26.45%), and coleoptericins (n = 38; 24.52%) were described based on their physicochemical and structural characteristics, as well as their sequence relationship to other insect HDPs. Therefore, the Scarabaeidae family is a complex and rich group of insects with a great diversity of antimicrobial peptides with potential antimicrobial activity.
MicroRNA Dysregulation in Canine Meningioma: RT-qPCR Analysis of Formalin-Fixed Paraffin-Embedded Samples
Authors: Foiani Greta , Guelfi Gabriella , Mandara Maria Teresa
Published: July 2021

MicroRNAs (miRNAs) are small non-coding RNAs that play key roles in tumorigenesis as modulators of cell signaling pathways. miRNA expression has been found to be dysregulated in several human and canine tumors, but data are not yet available on canine meningioma. In this study, we analyzed the expression of 12 miRNAs (i.e. miR-335, miR-200a, miR-98, miR-96, miR-190a, miR-29c, miR-219-5p, miR-155, miR-146a, miR-145, miR-136, miR-451) by RT-qPCR in a series of 41 formalin-fixed, paraffin-embedded canine meningiomas, and normal arachnoid samples. We identified 8 dysregulated miRNAs that might be involved in canine meningioma pathogenesis. Five miRNAs (i.e. miR-96, miR-145, miR-335, miR-200a, miR-29c), were downregulated in tumor samples and 3 (i.e. miR-136, miR-155, miR-146a) were upregulated. Moreover, miR-200a was overexpressed in grade III compared to grade I and grade II meningiomas, suggesting that it might have a dual role in tumor initiation and progression. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses suggest that dysregulated miRNAs might influence cellular processes and pathways mainly involved in tumor cell migration, extracellular matrix interactions, cell proliferation, and inflammatory responses. The characterization of miRNA functions in canine meningiomas is needed to assess their potential clinical utility, also in view of the relevance of the dog as a potential spontaneous animal model of human disease.
Post-transcriptional gene silencing of CYP76AD controls betalain biosynthesis in bracts of bougainvillea
Authors: Ohno Sho , Makishima Rikako , Doi Motoaki
Published: July 2021

Betalain is one of four major plant pigments and shares some features with anthocyanin; however, no plant has been found to biosynthesize both pigments. Previous studies have reported that anthocyanin biosynthesis in some plants is regulated by post-transcriptional gene-silencing (PTGS), but the importance of PTGS in betalain biosynthesis remains unclear. In this study, we report the occurrence of PTGS in betalain biosynthesis in bougainvillea (Bougainvillea peruviana) ‘Thimma’, which produces bracts of three different color on the same plant, namely pink, white, and pink-white. This resembles the unstable anthocyanin pigmentation phenotype that is associated with PTGS, and hence we anticipated the presence of PTGS in the betalain biosynthetic pathway. To test this, we analysed pigments, gene expression, small RNAs, and transient overexpression. Our results demonstrated that PTGS of BpCYP76AD1, a gene encoding one of the betalain biosynthesis enzymes, is responsible for the loss of betalain biosynthesis in ‘Thimma’. Neither the genetic background nor DNA methylation in the BpCYP76AD1 sequence could explain the induction of PTGS, implying that another locus controls the unstable pigmentation. Our results indicate that naturally occurring PTGS contributes to the diversification of color patterns not only in anthocyanin biosynthesis but also in betalain biosynthesis.
Mitigating the Impact of Reemergence From a Pandemic on Healthcare
Authors: Hall Patricia L
Published: July 2021

Healthcare workers have never faced a medical crisis that compares to the coronavirus disease-2019 pandemic. This modern-day pandemic fight draws parallels to a war. Because of these similarities, it would make sense that the experiences frontline providers have when transitioning to a normal healthcare routine would emulate experiences service members voice when reintegrating home from a battlefield. These common experiences include a unified mission, an exhausting, adrenaline-packed responsibility, and a celebrity-like status to the public. The pandemic response consumed healthcare with one united mission, but as we reemerge from the pandemic and restore other aspects of our healthcare system, multiple missions develop and compete. Returning to a common routine and regular status can manifest feelings of disappointment in healthcare workers’ everyday lives and career choices and lead to a reexamination of priorities and professions. As an organization with a focus on high reliability, mitigating the harm to staff and delivery system may be our new priority. The risk of not facing this situation head on is a potential exodus of seasoned professionals contemplating their future and selecting other career paths, thus draining the current institutional knowledge and potentially deterring future generations from healthcare. Leaders in the healthcare industry need to take a proactive stance in addressing this reemergence. Integrated, proactive programming is needed utilizing evidence-based resiliency training from professional organizations such as the National Alliance on Mental Illness, the Department of Health and Human Services’ Substance Abuse and Mental Health Services Administration, as well as the existing Department of Defense programs. The Veterans Affairs has the backbone to develop and offer these programs and make a positive difference with Employee Whole Health efforts. Organized, evidence-based programming such as second victim education, mindfulness, and other personal skill building could be key to improving the lifelong well-being of our caregivers.
Method for Teaching Life-Saving Combat First-Aid Skills With live–actor Patients Using a Wearable Training Apparatus
Authors: Lv Mingrui , Jia Yijun , Zong Zhaowen , Jiang Renqing , Du Wenqiong , Zhang Lin , Ye Zhao , Zhong Xin
Published: July 2021

Introduction

Training combat personnel in combat first-aid skills has faced many challenges over time, such as the need to combine tactics with medicine and to overcome combat personnel’s lack of medical background knowledge. Therefore, many simulation methods are currently being developed, each of which has its advantages and disadvantages. In this study, a combined simulation method involving live–actor patients using a wearable training apparatus was developed, and the effects of this method were observed.

Materials and Methods

Focusing on the major causes of preventable deaths among victims killed in action, wearable training apparatuses simulating massive hemorrhage, airway obstruction, and tension pneumothorax were designed and produced. Methods of simulating these three injury types using live–actor patients with these training apparatuses were developed, and medical teachers evaluated the simulation effects. The live–actor patients were incorporated into a tactical scenario to train and test nonmedical and medical students in year 3, respectively. High-fidelity simulator-based training and traditional training without simulation served as the control. A post-training survey using a 7-point Likert scale evaluated the trainees’ feelings toward these training approaches.

Results

Three types of training apparatuses were developed to simulate three life-threatening injuries, and the simulation effects of the live–actor patients using these apparatuses were highly recognized by medical teachers. Both live–actor patients and high-fidelity simulator-based training improved performance significantly more than traditional training. However, the improvement due to training with live–actor patients was greater than that due to high-fidelity simulator-based training for nonmedical students, whereas there was no difference between these two simulation methods for medical students. A post-training survey revealed that all the trainees were confident in practicing first-aid skills after training, and they all agreed that live–actor patients could combine tactical situations with first aid better than high-fidelity simulators. The nonmedical students strongly agreed that live–actor patients were more helpful in the training of injury evaluation than high-fidelity simulators.

Conclusions

The method using wearable training apparatus-based live–actor patients was satisfying and effective for teaching life-saving combat first-aid skills, especially for nonmedical students.
Leadership Training in Medicine—12 Years of Experience From the Feagin Leadership Program
Authors: Nosé Brent , Sankey Eric , Moris Dimitrios , Doty Joe , Taylor Dean
Published: July 2021

Introduction

Increasingly, physicians find themselves in demanding leadership positions. However, leadership education for medical trainees remains lacking with most physicians reporting that they are ill-equipped to tackle the challenges of leadership. Here, we set out to describe the Feagin Leadership Program (FLP) and assess its reception and impact on trainees over the past 12 years.

Materials and Methods

During the 1-year FLP, selected scholars from Duke University, Wake Forest University, and the University of North Carolina participate in five leadership sessions, individual coaching, a leadership forum, and a multidisciplinary team–based capstone project. A 28-question survey with six optional free-response questions was distributed to the Feagin Alumni Network, and descriptive statistics were assessed.

Results

Since its founding, 212 scholars have graduated from the FLP and 117 (55%) alumni have gone on to surgical specialties. A survey was distributed among all Feagin alumni. A total of 56 (26%) surveys were completed. Forty-three percent (n = 24) had held at least one leadership position since completing the FLP. When asked about the impact of their experience, 96% (n = 54) said that the program encouraged them to pursue a position of leadership within their field, 95% (n = 53) stated that it prepared them for such a position, and 93% (n = 52) stated that the program positively influenced their decision to be involved with current or future positions of leadership.

Conclusions

Over the last 12 years, the FLP has demonstrated a high perceived impact on personal growth, leadership proficiency, and the decision to pursue leadership positions in medicine. The current dearth of leadership education for surgical trainees can best be addressed with models such as the FLP, with adoption benefiting medical trainees, the medical community, and patients they serve.
Lessons Learned During Prolonged Care of Combat Casualties by a Minimally Manned Surgical Team
Authors: Lesperance Richard N , Adamson Steven , Gurney Jennifer M
Published: July 2021

In the current deployed environment, small teams are dispersed to provide damage control surgical capabilities within an hour of injury. Given the well-developed evacuation system, these teams do not typically have a significant patient hold capability. Improved understanding of the shortfalls and problems encountered when caring for combat casualties in prolonged care situations will facilitate improved manning, training, and equipping of these resource-limited teams. We present the case of two critically injured soldiers who were evacuated to a 10-person split Forward Surgical Team (FST) during a weather system that precluded further evacuation. The casualties underwent damage control procedures necessitating temporary abdominal closures. The FST had to organize itself to provide intensive care significantly longer than traditional timelines for this role of care. Additionally, most team members had scarce critical care experience. An after-action review confirmed that most team members felt that they had not received adequate pre-mission training in postoperative intensive care and were not comfortable managing ventilated patients. In the current mature theaters of operations, there are robust evacuation capabilities, and presentations of scenarios like that are rare. However, as combat casualty care becomes increasingly austere and remote, small surgical teams need to train and be equipped to provide care outside of normal operation and doctrinal limits, including robust team cross-training. Incorporating principles of the prolonged care of combat casualties into the training of military surgeons will improve preparedness for these challenging situations.
Leadership Root Cause Analysis: Using a Formal Analysis Tool to Dissect and Promote Intrusive Leadership in a U.S. Naval Hospital
Authors: Paz David A , Thurber Jean A , Judy Cynthia L , Quast Timothy M
Published: July 2021

Intrusive leadership is a method that looks for signs that might indicate a problem within or outside of the workplace that can affect a member’s performance and, subsequently, the mission. Our scenario demonstrates how intrusive leadership can identify potential problems which, when coupled with accountability, can prevent more significant complications.
An updated distance to the Cygnus Loop based on Gaia Early DR3
Authors: Fesen Robert A , Weil Kathryn E , Cisneros Ignacio , Blair William P , Raymond John C
Published: July 2021

We present a revised distance to the Cygnus Loop supernova remnant of 725 ± 15 pc based on Gaia Early Data Release 3 parallax measurements (EDR3) for several stars previously found to be located either inside or behind the supernova based on the presence of high-velocity absorption lines in their spectra. This revised distance estimate and error means the Cygnus Loop remnant now has an estimated distance uncertainty comparable to that of its ≃18 pc radius.
Influence of the Galactic bar on the kinematics of the disc stars with Gaia EDR3 data
Authors: Melnik A M , Dambis A K , Podzolkova E N , Berdnikov L N
Published: July 2021

A model of the Galaxy with the outer ring R1R2 can explain the observed distribution of the radial, VR, and azimuthal, VT, velocity components along the Galactocentric distance, R, derived from the Gaia EDR3 data. We selected stars from the Gaia EDR3 catalogue with reliable parallaxes, proper motions, and line-of-sight velocities lying near the Galactic plane, |z| < 200 pc, and in the sector of the Galactocentric angles |θ| < 15° and calculated the median velocities VR and VT in small bins along the distance R. The distribution of observed velocities appears to have some specific features: the radial velocity VR demonstrates a smooth fall from +5 km s−1 at the distance of R ≈ R0 − 1.5 kpc to −3 km s−1 at R ≈ R0 + 1.0 kpc while the azimuthal velocity VT shows a sharp drop by 7 km s−1 in the distance interval R0 < R < R0 + 1.0 kpc, where R0 is the solar Galactocentric distance. We build a model of the Galaxy including bulge, bar, disc, and halo components, which reproduces the observed specific features of the velocity distribution in the Galactocentric distance interval |R − R0| < 1.5 kpc. The best agreement corresponds to the time 1.8 ± 0.5 Gyr after the start of the simulation. A model of the Galaxy with the bar rotating at the angular velocity of Ωb = 55 ± 3 km s−1 kpc−1, which sets the OLR of the bar at the distance of R0 − 0.5 ± 0.4 kpc, provides the best agreement between the model and observed velocities. The position angle of the bar, θb, corresponding to the best agreement between the model and observed velocities is θb = 45 ± 15°.
The Kennicutt–Schmidt law and the main sequence of galaxies in Newtonian and milgromian dynamics
Authors: Zonoozi Akram Hasani , Lieberz Patrick , Banik Indranil , Haghi Hosein , Kroupa Pavel
Published: July 2021

The Kennicutt–Schmidt law is an empirical relation between the star formation rate surface density (ΣSFR) and the gas surface density (Σgas) in disc galaxies. The relation has a power-law form $\Sigma _{\text{SFR}} \propto \Sigma _{\text{gas}}^{n}$. Assuming that star formation results from gravitational collapse of the interstellar medium, ΣSFR can be determined by dividing Σgas by the local free-fall time tff. The formulation of tff yields the relation between ΣSFR and Σgas, assuming that a constant fraction (εSFE) of gas is converted into stars every tff. This is done here for the first time using Milgromian dynamics (MOND). Using linear stability analysis of a uniformly rotating thin disc, it is possible to determine the size of a collapsing perturbation within it. This lets us evaluate the sizes and masses of clouds (and their tff) as a function of Σgas and the rotation curve. We analytically derive the relation $\Sigma _{\text{SFR}} \propto \Sigma _{\text{gas}}^{n}$ both in Newtonian and Milgromian dynamics, finding that n = 1.4. The difference between the two cases is a change only to the constant pre-factor, resulting in increased ΣSFR of up to 25 per cent using MOND in the central regions of dwarf galaxies. Due to the enhanced role of disc self-gravity, star formation extends out to larger galactocentric radii than in Newtonian gravity, with the clouds being larger. In MOND, a nearly exact representation of the present-day main sequence of galaxies is obtained if $\epsilon _{\text{SFE}} = \text{constant} \approx 1.1{{\ \rm per\ cent}}$. We also show that empirically found correction terms to the Kennicutt–Schmidt law are included in the here presented relations. Furthermore, we determine that if star formation is possible, then the temperature only affects ΣSFR by at most a factor of $\sqrt{2}$.
Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network
Authors: Liang Ying , Lu Qi , Li Wei , Zhang Dapeng , Zhang Fanglin , Zou Qingping , Chen Lu , Tong Ying , Liu Mengxing , Wang Shaoxuan , Li Wenxuan , Ren Xiaoguang , Xu Peng , Yang Zhicong , Dong Shihua , Zhang Baolong , Huang Yanni , Li Daqiang , Wang Hailin , Yu Wenqiang
Published: July 2021

Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment.
Genetic vulnerabilities upon inhibition of DNA damage response
Authors: Wang Chao , Tang Mengfan , Chen Zhen , Nie Litong , Li Siting , Xiong Yun , Szymonowicz Klaudia Anna , Park Jeong-Min , Zhang Huimin , Feng Xu , Huang Min , Su Dan , Hart Traver , Chen Junjie
Published: July 2021

Because of essential roles of DNA damage response (DDR) in the maintenance of genomic integrity, cellular homeostasis, and tumor suppression, targeting DDR has become a promising therapeutic strategy for cancer treatment. However, the benefits of cancer therapy targeting DDR are limited mainly due to the lack of predictive biomarkers. To address this challenge, we performed CRISPR screens to search for genetic vulnerabilities that affect cells’ response to DDR inhibition. By undertaking CRISPR screens with inhibitors targeting key DDR mediators, i.e. ATR, ATM, DNAPK and CHK1, we obtained a global and unbiased view of genetic interactions with DDR inhibition. Specifically, we identified YWHAE loss as a key determinant of sensitivity to CHK1 inhibition. We showed that KLHL15 loss protects cells from DNA damage induced by ATM inhibition. Moreover, we validated that APEX1 loss sensitizes cells to DNAPK inhibition. Additionally, we compared the synergistic effects of combining different DDR inhibitors and found that an ATM inhibitor plus a PARP inhibitor induced dramatic levels of cell death, probably through promoting apoptosis. Our results enhance the understanding of DDR pathways and will facilitate the use of DDR-targeting agents in cancer therapy.
Infectious Diseases Learning Unit: Understanding Advances in the Treatment of Latent Tuberculosis Infection Among People With Human Immunodeficiency Virus
Authors: Mehtani Nicky J , Puryear Sarah , Pham Paul , Dooley Kelly E , Shah Maunank
Published: July 2021

Tuberculosis (TB) remains the leading cause of death among people with human immunodeficiency virus (PWH). The diagnosis of latent TB infection (LTBI) and treatment with TB preventative therapy (TPT) can reduce morbidity and mortality in this population. Historically, isoniazid has been recommended for TPT in PWH due to the absence of drug-drug interactions with most antiretroviral therapy (ART). However, newer rifamycin-based regimens are safer, shorter in duration, associated with improved adherence, and may be as or more effective than isoniazid TPT. Current guidelines have significant heterogeneity in their recommendations for TPT regimens and acceptability of drug interactions with modern ART. In this Infectious Diseases learning unit, we review common questions on diagnosis, treatment, and drug interactions related to the management of LTBI among PWH.
Use of Metagenomic Next-Generation Sequencing to Identify Pathogens in Pediatric Osteoarticular Infections
Authors: Ramchandar Nanda , Burns Jessica , Coufal Nicole G , Pennock Andrew , Briggs Benjamin , Stinnett Rita , Bradley John , Arnold John , Liu George Y , Pring Maya , Upasani Vidyadhar V , Rickert Kathleen , Dimmock David , Chiu Charles , Farnaes Lauge , Cannavino Christopher
Published: July 2021

Background

Osteoarticular infections (OAIs) are frequently encountered in children. Treatment may be guided by isolation of a pathogen; however, operative cultures are often negative. Metagenomic next-generation sequencing (mNGS) allows for broad and sensitive pathogen detection that is culture-independent. We sought to evaluate the diagnostic utility of mNGS in comparison to culture and usual care testing to detect pathogens in acute osteomyelitis and/or septic arthritis in children.

Methods

This was a single-site study to evaluate the use of mNGS in comparison to culture to detect pathogens in acute pediatric osteomyelitis and/or septic arthritis. Subjects admitted to a tertiary children’s hospital with suspected OAI were eligible for enrollment. We excluded subjects with bone or joint surgery within 30 days of admission or with chronic osteomyelitis. Operative samples were obtained at the surgeon’s discretion per standard care (fluid or tissue) and based on imaging and operative findings. We compared mNGS to culture and usual care testing (culture and polymerase chain reaction [PCR]) from the same site.

Results

We recruited 42 subjects over the enrollment period. mNGS of the operative samples identified a pathogen in 26 subjects compared to 19 subjects in whom culture identified a pathogen. In 4 subjects, mNGS identified a pathogen where combined usual care testing (culture and PCR) was negative. Positive predictive agreement and negative predictive agreement both were 93.0% for mNGS.

Conclusions

In this single-site prospective study of pediatric OAI, we demonstrated the diagnostic utility of mNGS testing in comparison to culture and usual care (culture and PCR) from operative specimens.
Characteristics of High-Titer Convalescent Plasma and Antibody Dynamics After Administration in Patients With Severe Coronavirus Disease 2019
Authors: Bainbridge Emma D , Hsue Priscilla Y , Esensten Jonathan H , Lynch Kara L , Hendrickson Carolyn M , Doernberg Sarah B , Fung Monica , Chin-Hong Peter , Di Germanio Clara , Norris Philip J , Simmons Graham , Glidden David V , Luetkemeyer Anne F
Published: July 2021

We characterized the antibody composition of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) and the immunologic responses of hospitalized COVID-19 patients after receiving CCP or nonimmune fresh frozen plasma. Despite selection of CCP with significantly higher total immunoglobulin G than recipients, neutralizing antibody levels did not differ between donor plasma and CCP recipients.
Axonal dysfunction is associated with interferon-γ levels in childhood-onset systemic lupus erythematosus: a multivoxel magnetic resonance spectroscopy study
Authors: Frittoli Renan Bazuco , Pereira Danilo Rodrigues , Lapa Aline Tamires , Postal Mariana , Sinicato Nailu Angelica , Fernandes Paula Teixeira , Cendes Fernando , Castellano Gabriela , Rittner Leticia , Marini Roberto , Niewold Timothy B , Appenzeller Simone
Published: July 2021

Objective

Axonal/neuronal damage has been shown to be a pathological finding that precedes neuropsychiatric manifestations in SLE. The objective of this study was to determine the presence of axonal dysfunction in childhood-onset SLE patients (cSLE) and to determine clinical, immunological and treatment features associated with its occurrence.

Methods

We included 86 consecutive cSLE patients [median age 17 (range 5–28) years] and 71 controls [median age 18 (5–28) years]. We performed proton magnetic resonance spectroscopic imaging using point resolved spectroscopy sequence over the superior–posterior region of the corpus callosum and signals from N-acetylaspartate (NAA), choline-based (CHO), creatine-containing (Cr), myo-inositol (mI), glutamate, glutamine and lactate were measured and metabolites/Cr ratios were determined. Complete clinical, laboratory and neurological evaluations were performed in all subjects. Serum IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, TNF-α and INF-γ cytokine levels, antiribosomal P protein antibodies (anti-P) and S100β were measured by ELISA using commercial kits. Data were compared by non-parametric tests.

Results

NAA/Cr ratios (P = 0.035) and lactate/Cr ratios (P = 0.019) were significantly decreased in cSLE patients when compared with controls. In multivariate analysis, IFN-γ levels [odds ratio (OR) = 4.1; 95% CI: 2.01, 7.9] and depressive symptoms (OR = 1.9; 95% CI: 1.1, 3.2) were associated with NAA/Cr ratio. Increased CHO/Cr was associated with the presence of cognitive impairment (OR = 3.4; 95% CI: 2.034, 5.078; P < 0.001). mI/Cr ratio correlated with cumulative glucocorticoids dosage (r = 0.361, P = 0.014).

Conclusion

NAA and CHO ratios may be useful as biomarkers in neuropsychiatric cSLE. Longitudinal studies are necessary to determine whether they predict structural damage.