bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase transition of shocked water up to 6 GPa: Transmittance investigation*
Authors: Wu Lang , Ren Yue-Hong , Liao Wen-Qiang , Huang Xi-Chen , Liu Fu-Sheng , Zhang Ming-Jian , Sun Yan-Yun
Published: December 2020

The phase transition behaviors of the shocked water are investigated by employing an optical transmittance in-situ detection system. Based on the light scattering theory and phase transformation kinetics, the phase transition mechanism of the water under multiple shocks is discussed. The experimental data indicate that the evolution of the transmittance of the shocked water can be broadly divided into three stages: relaxation stage, decline stage, and recovery stage. In the early stage of the phase transition, the new phase particles began to form around the quartz/window interface. It should be mentioned that the water/ice phase boundary seems to move toward the liquid region in one experiment of this work. Due to the new phase core being much smaller than the wavelength of the incident light, the transmittance of the sample within the relaxation stage remains steady. The decline stage can be divided into the rapid descent stage and the slow descent stage in this work, which is considered as the different growth rates of the new phase particle under different shock loadings. The recovery stage is attributed to the emergence of the new phase particles which are bigger than the critical value. However, the influence of the size growth and the population growth of the new phase particles on the transmittance restrict each other, which may be responsible for the phenomenon that the transmittance curve does not return to the initial level.
Combined effects of carrier scattering and Coulomb screening on photoluminescence in InGaN/GaN quantum well structure with high In content*
Authors: Li Rui , Xu Ming-Sheng , Wang Peng , Wang Cheng-Xin , Qu Shang-Da , Shi Kai-Ju , Wei Ye-Hui , Xu Xian-Gang , Ji Zi-Wu
Published: December 2020

Photoluminescence (PL) spectra of two different green InGaN/GaN multiple quantum well (MQW) samples S1 and S2, respectively with a higher growth temperature and a lower growth temperature of InGaN well layers are analyzed over a wide temperature range of 6 K–330 K and an excitation power range of 0.001 mW–75 mW. The excitation power-dependent PL peak energy and linewidth at 6 K show that in an initial excitation power range, the emission process of the MQW is dominated simultaneously by the combined effects of the carrier scattering and Coulomb screening for both the samples, and both the carrier scattering effect and the Coulomb screening effect are stronger for S2 than those for S1; in the highest excitation power range, the emission process of the MQWs is dominated by the filling effect of the high-energy localized states for S1, and by the Coulomb screening effect for S2. The behaviors can be attributed to the fact that sample S2 should have a higher amount of In content in the InGaN well layers than S1 because of the lower growth temperature, and this results in a stronger component fluctuation-induced potential fluctuation and a stronger well/barrier lattice mismatch-induced quantum-confined Stark effect. This explanation is also supported by other relevant measurements of the samples, such as temperature-dependent peak energy and excitation-power-dependent internal quantum efficiency.
Efficient realization of daytime radiative cooling with hollow zigzag SiO2 metamaterials*
Authors: Yao Huawei , Wang Xiaoxia , Yin Huaiyuan , Jia Yuanlin , Gao Yong , Wang Junqiao , Fan Chunzhen
Published: December 2020

A tunable selective emitter with hollow zigzag SiO2 metamaterials, which are deposited on Si3N4 and Ag film, is proposed and numerically investigated for achieving excellent radiative cooling effects. The average emissivity reaches a high value of 98.7% in the atmospheric window and possesses a high reflectivity of 92.0% in the solar spectrum. To reveal the enhanced absorptivity, the confined electric field distribution is investigated, and it can be well explained by moth eye effects. Moreover, tunable emissivity can also be initiated with different incident angles and it stays above 83% when the incident angle is less than 80°, embodying the excellent cooling performance in the atmospheric transparency window. Its net cooling power achieves 100.6 W⋅m−2, with a temperature drop of 13°, and the cooling behavior can persist in the presence of non-radiative heat exchange conditions. Therefore, high and tunable selective emitters based on our designed structure could provide a new route to realizing high-performance radiative cooling. This work is also of great significance for saving energy and environmental protection.
The signature of internal variability in the terrestrial carbon cycle
Authors: Bonan Gordon B , Lombardozzi Danica L , Wieder William R
Published: December 2020

Uncertainty in model initial states produces uncertainty in climate simulations because of unforced variability internal to the climate system. Climate scientists use initial-condition ensembles to separate the forced signal of climate change from the unforced internal variability. Our analysis of an 11-member initial-condition ensemble from the Community Earth System Model Version 2 that spans the period 1850–2014 shows that a similar ensemble approach is needed to robustly assess trends in the terrestrial carbon cycle. Uncertainty in model initialization gives rise to internal variability that masks trends in carbon fluxes, and also creates spurious unforced trends, during the period 1960–2014 across North America, meaning that a single model realization can diverge from the observational record or from other models simply because of random behavior. The forced response is, however, evident in the ensemble mean and emerges from the noise of unforced variability at decadal timescales. Our results suggest that trends in the observational record must be interpreted with caution because of multiple possible histories that would have been observed if the sequence of internal variability had unfolded differently. Furthermore, internal variability produces irreducible uncertainty in the carbon cycle, leading to ambiguity in the magnitude and sign of carbon cycle trends, especially at small spatial scales and short timescales. The small spread in initial land carbon pools at 1850 suggests that internal climate variability arising from atmospheric and oceanic initialization, not the biogeochemical initialization, is the predominant cause of carbon cycle variability among ensemble members. Initial-condition ensembles with other Earth system models are needed to develop a multi-model understanding of internal variability in the terrestrial carbon cycle.
Emergence of massless Froḧlich polarons in two-dimensional semi-metals on polar substrates
Authors: Banerjee Swapnonil
Published: December 2020

We consider the polaron dynamics driven by Froḧlich type, long wavelength dominated electron-phonon interaction at zero temperature, for three different semi-metals: single and bilayer graphene, and semi-Dirac, all grown on polar substrates such as, SiC. Single layer graphene (henceforth called SL graphene), bilayer graphene (henceforth called BL graphene), and semi-Dirac have two dimensional band-structures with point Fermi surfaces in their natural undoped conditions. When these materials are grown on polar substrates, their electrons can interact with the optical phonons (LO) at the surface of the substrates. That gives rise to the possibility of polaron formation in the context of these semi-metals, although they themselves are non-polar. Starting from the Froḧlich type electron-phonon interaction Hamiltonian, perturbation theory is employed to calculate the self energy of the electron due to polaron formation for the three aforementioned systems. The electron self energy, or the polaron energy, calculated analytically for BL graphene, is shown to vary linearly with the electron momentum for small electron momenta. Whereas for ordinary polar crystals (both two and three dimensional), for small electron momentum, the polaron energy is quadratic leading to the mass correction of the electron, for BL graphene the polaron energy disperses linearly, rendering the massive BL graphene electrons effectively massless. Energies for Froḧlich polarons in SL graphene and semi-Dirac on polar substrates, are numerically evaluated. Also, the electron relaxation rate, related to the imaginary part of the analytically continued electron self energy expression, is calculated for the three systems.
Identifying anti-coronavirus peptides by incorporating different negative datasets and imbalanced learning strategies
Authors: Pang Yuxuan , Wang Zhuo , Jhong Jhih-Hua , Lee Tzong-Yi
Published: December 2020

As the current worldwide outbreaks of the SARS-CoV-2, it is urgently needed to develop effective therapeutic agents for inhibiting the pathogens or treating the related diseases. Antimicrobial peptides (AMP) with functional activity against coronavirus could be a considerable solution, yet there is no research for identifying anti-coronavirus (anti-CoV) peptides with the computational approach. In this study, we first investigated the physiochemical and compositional properties of the collected anti-CoV peptides by comparing against three other negative sets: antivirus peptides without anti-CoV function (antivirus), regular AMP without antivirus functions (non-AVP) and peptides without antimicrobial functions (non-AMP). Then, we established classifiers for identifying anti-CoV peptides between different negative sets based on random forest. Imbalanced learning strategies were adopted due to the severe class-imbalance within the datasets. The geometric mean of the sensitivity and specificity (GMean) under the identification from antivirus, non-AVP and non-AMP reaches 83.07%, 85.51% and 98.82%, respectively. Then, to pursue identifying anti-CoV peptides from broad-spectrum peptides, we designed a double-stages classifier based on the collected datasets. In the first stage, the classifier characterizes AMPs from regular peptides. It achieves an area under the receiver operating curve (AUCROC) value of 97.31%. The second stage is to identify the anti-CoV peptides between the combined negatives of other AMPs. Here, the GMean of evaluation on the independent test set is 79.42%. The proposed approach is considered as an applicable scheme for assisting the development of novel anti-CoV peptides. The datasets and source codes used in this study are available at https://github.com/poncey/PreAntiCoV.
A space-time continuum in DBS: structural and functional advances in Parkinson’s disease
Authors: Starr Philip , Little Simon
Published: December 2020

This scientific commentary refers to ‘Modulation of beta bursts in subthalamic sensorimotor circuits predicts improvement in bradykinesia’, by Kehnemouyi et al. (doi:10.1093/brain/awaa394).
Introduction of user fee for language interpretation: effects on use of interpreters in Danish health care
Authors: Michaëlis Camilla , Krasnik Allan , Norredam Marie
Published: December 2020

Amendments to the Danish Health Act were introduced in 2018 that stated immigrant patients who have resided in Denmark for more than 3 years have to pay user fees for interpretation in health care. The aim of the study was to explore, how the use of interpreters was affected by the introduction of user fees for interpretation. Results showed a considerable decrease in interpretation services following the introduction of the fee. It is likely to assume that the reduced utilization of interpretation services is highly related to the fee. Further research is needed about the consequences of underutilization of interpretation services.
Federated learning improves site performance in multicenter deep learning without data sharing
Authors: Sarma Karthik V , Harmon Stephanie , Sanford Thomas , Roth Holger R , Xu Ziyue , Tetreault Jesse , Xu Daguang , Flores Mona G , Raman Alex G , Kulkarni Rushikesh , Wood Bradford J , Choyke Peter L , Priester Alan M , Marks Leonard S , Raman Steven S , Enzmann Dieter , Turkbey Baris , Speier William , Arnold Corey W
Published: December 2020

Objective

To demonstrate enabling multi-institutional training without centralizing or sharing the underlying physical data via federated learning (FL).

Materials and Methods

Deep learning models were trained at each participating institution using local clinical data, and an additional model was trained using FL across all of the institutions.

Results

We found that the FL model exhibited superior performance and generalizability to the models trained at single institutions, with an overall performance level that was significantly better than that of any of the institutional models alone when evaluated on held-out test sets from each institution and an outside challenge dataset.

Discussion

The power of FL was successfully demonstrated across 3 academic institutions while avoiding the privacy risk associated with the transfer and pooling of patient data.

Conclusion

Federated learning is an effective methodology that merits further study to enable accelerated development of models across institutions, enabling greater generalizability in clinical use.
Effects of Ascogregarina culicis (Eugregarinorida: Lecudinidae) on Mosquito Size and Dengue Virus Infection in Aedes aegypti (Diptera: Culicidae)
Authors: Thongsripong Panpim , Wesson Dawn M
Published: December 2020

Dengue virus infection, transmitted via mosquito bites, poses a substantial risk to global public health. Studies suggest that the mosquito’s microbial community can profoundly influence vector-borne pathogen transmissions, including dengue virus. Ascogregarina culicis (Ross) of the phylum Apicomplexa is among the most common parasites of Aedes aegypti (Linnaeus), the principal vector of dengue. Despite a high prevalence worldwide, including in the areas where dengue is endemic, the impact of A. culicis on Ae. aegypti vector competence for dengue virus is unknown. This study aimed to investigate the effects of A. culicis infection on mosquito size and fitness, as measured by wing length, and the susceptibility to dengue virus infection in Ae. aegypti. Our results showed that there was no statistically significant difference in wing lengths between Ae. aegypti infected and not infected with A. culicis. Furthermore, A. culicis infection did not significantly affect dengue virus infection or disseminated infection rate. However, there was a significant association between shorter wings and higher dengue virus infection rate, whereby a 0.1-mm increase in wing length decreased the odds of the mosquito being infected by 32%. Thus, based on our result, A. culicis infection does not influence the body size and dengue virus infection in Ae. aegypti. This study helps to shed light on a common but neglected eukaryotic mosquito parasite.
Zymosan enhances in vitro phagocyte function and the immune response of mice infected with Paracoccidioides brasiliensis
Authors: Silva G S , Silva D A , Guilhelmelli F , Jerônimo M S , Cardoso-Miguel M R D , Bürgel P H , Castro R J A , de Oliveira S A M , Silva-Pereira I , Bocca A L , Tavares A H
Published: December 2020

Paracoccidioides brasiliensis is the major etiologic agent of Paracoccidioidomycosis (PCM), the most frequent human deep mycosis in Latin America. It is proposed that masking of β-glucan in P. brasiliensis cell wall is a critical virulence factor that contributes to the development of a chronic disease characterized by a long period of treatment, which is usually toxic. In this context, the search for immunomodulatory agents for therapeutic purposes is highly desirable. One strategy is to use pattern recognition receptors (PRRs) ligands to stimulate the immune response mediated by phagocytes. Here, we sought to evaluate if Zymosan, a β-glucan-containing ligand of the PRRs Dectin-1/TLR-2, would enhance phagocyte function and the immune response of mice challenged with P. brasiliensis. Dendritic cells (DCs) infected with P. brasiliensis and treated with Zymosan showed improved secretion of several proinflammatory cytokines and expression of maturation markers. In addition, when cocultured with splenic lymphocytes, these cells induced the production of a potential protective type 1 and 17 cytokine patterns. In macrophages, Zymosan ensued a significant fungicidal activity associated with nitric oxide production and phagolysosome acidification. Importantly, we observed a protective effect of Zymosan-primed DCs delivered intranasally in experimental pulmonary PCM. Overall, our findings support the potential use of β-glucan-containing compounds such as Zymosan as an alternative or complementary antifungal therapy.

Lay Summary

We report for the first time that Paracoccidioides brasiliensis-infected phagocytes treated with Zymosan (cell wall extract from bakers' yeast) show enhanced cytokine production, maturation, and fungal killing. Also, Zymosan-primed phagocytes induce a protective immune response in infected mice.
Humanizing the Morbidity and Mortality Conference
Authors: Pang Sharon , Warraich Haider J.
Published: December 2020

Morbidity and mortality conferences (MMCs) are a long-held legacy institution in academic medicine that enable medical providers and hospital administrators to learn from systemic and individual errors, thereby leading to improved medical care. Originally, this forum had 1 major role—education. The MMC evolved and a second key role was added: quality improvement. In the wake of the 2020 COVID-19 pandemic, a second evolution—one that will humanize the MMC—is required. The pandemic emphasizes the need to use MMCs not only as a place to discuss errors but also as a place for medical providers to reflect on lives lost. The authors’ review of the literature regarding MMCs indicates that most studies focus on enabling MMCs to become a forum for quality improvement, while none have emphasized the need to humanize MMCs to decrease medical provider burnout and improve patient satisfaction. Permitting clinicians to be human on the job requires restructuring the MMC to provide a space for reflection and, ultimately, defining a new purpose and charge for the MMC.

The authors have 3 main recommendations. First, principles of humanism such as compassion, empathy, and respect, in particular, should be incorporated into traditional MMCs. Second, shorter gatherings devoted to giving clinicians the opportunity to focus on their humanity should be arranged. Third, an MMC focused entirely on the human aspects of medical care should be periodically arranged to provide an outlet for storytelling, artistic expression, and reflection.

Humanizing the MMC—a core symposium in clinical medicine worldwide—could be the first step in revitalizing the spirit at the heart of medicine, one dedicated to health and healing. This spirit, which has been eroding as the field of medicine becomes increasingly corporate in structure and mission, is as essential during peaceful times in health care as during a pandemic.
Everyday Heroism: Maintaining Organizational Cultures of Wellness and Inclusive Excellence Amid Simultaneous Pandemics
Authors: Fassiotto Magali , Valantine Hannah , Shanafelt Tait , Maldonado Yvonne
Published: December 2020

Health care professionals and the institutions in which they work are being stretched to their limits amidst the current COVID-19 pandemic. At the same time, a second longstanding pandemic has been brought to the fore: the entrenched system of racial injustice and oppression. The first pandemic is new, and to date, substantial resources have been allocated to urgently addressing its mitigation; the second has a long history with inconsistent attention and resources but has recently been spotlighted more intensely than at any time in the nation’s recent past. The authors contend that these 2 simultaneous pandemics have brought forth the need for institutions in the United States to make a renewed commitment to respect, wellness, diversity, and inclusion. While investment and leadership in these domains have always been essential, these have largely been viewed as a “nice-to-have” option. The events of much of 2020 (most notably) have illustrated that committing to and investing in policies, programs, centers, and leadership to drive change in these domains are essential and a “need-to-have” measure. The authors outline the necessity of investing in the promotion of cultures of inclusive excellence at both individual and organizational levels to coordinate a united response to the simultaneous pandemics. It is in the interests of health care systems to consider the wellness of the workforce to overcome the longer-term economic, systemic, and social trauma that will likely occur for years to come at both the individual and institutional levels. Maintaining or augmenting investment is necessary despite the economic challenges the nation faces. Now is the time to cultivate resilience and wellness through a renewed commitment to cultures of respect, diversity, and inclusion. This commitment is urgently needed to support and sustain the health care workforce and maintain outstanding health care systems for future generations.
Novel Prescriptions From Medical Schools for Physician–Scientist Training and Engagement in the Twenty-First Century
Authors: Simpson Rolly L. , Cornfield David N. , Burris John E.
Published: December 2020

Physicians engaged in biomedical research are well positioned to directly focus the discovery process on human biology. However, the relative proportion of investigators engaged in both caring for patients and conducting research is decreasing. To address the dwindling numbers of physician–scientists nationally, the Burroughs Wellcome Fund created the Physician-Scientist Institutional Awards Program by dedicating 25 million dollars to new initiatives at 10 degree granting, accredited medical schools in North America, awarded on the basis of institutions’ proposals. The perceived barriers to physician–scientist training, program initiatives, and commitment to training a diverse group of future researchers were articulated in each application. In all, the Burroughs Wellcome Fund review committee considered 136 distinct proposals from 83 medical schools, representing 54% of all accredited medical schools in North America. Barriers identified by more than one-third of the applicant institutions included the absence of both mentors and role models, student indebtedness, institutional cultures that valued clinical care delivery above the discovery process, limited prior relevant research experience, and structural barriers that limited scheduling flexibility during training. Awards were granted to institutions with programs designed to be sustainable and overcome critical, prospectively identified barriers to training and retention of physician–scientists. Potential solutions from the 10 funded programs were focused on different stages of the training experience. Though a determination about the relative success of each of the initiatives will take many years, careful consideration of the barriers identified and more general application of specific program component may be beneficial in increasing the numbers of physicians actively involved in biomedical research.
Pedicled Split Hypogastric Flap (Superficial Inferior Epigastric Artery flap): A New Technique for Coverage of Nonadjacent Defects in the Hand
Authors: Sabapathy Shanmuganathan Raja , Senthilkumaran Murugesan , Mohan Monusha
Published: December 2020

Flap coverage of soft tissue defects on both surfaces of the hand or of nonadjacent defects in the hand is a challenge. Two flaps are needed or if a single flap is used, the intervening normal area or part of the flap must be deepithelialized or the flap tunneled under the normal bridge segment. We are presenting a new technique whereby the hypogastric flap based on the superficial inferior epigastric artery is split into 2 components for the coverage of such defects. The hypogastric flap is separated into a cutaneous component and an adipofascial component at the level of Scarpa fascia. The flaps are separated almost to the base to increase mobility. Now it can be used to cover 2 defects separated by 5 to 7 cm or for defects in the dorsum and the palm. We have used it in 3 patients, in 2 for the coverage of palmar and dorsal aspect of the hand and in one for the coverage of nonadjacent defects on the dorsum of the hand and distal forearm after postburn contracture release. We achieved good results with no flap-related complications.
Modified Oblique Triangular Neurovascular Island Flap Technique to Prevent the Development of Hooked Nail Deformity
Authors: Siritattamrong Wichit , Wongtrakul Saichol , Pookhang Samran , Siriwittayakorn Wuttipong
Published: December 2020

Hooked fingernail deformity can develop after any type of fingertip amputation. A more proximal amputation is associated with a higher probability of developing hooked fingernails. Proximal fingertip amputations with very short remaining nail beds are recommended for revision amputation with nail bed ablation. This procedure eliminates the possibility that the patient may have a functional nail. When the nail matrix is still retained, an oblique triangular neurovascular island flap may preserve the nail and digit length. At our institution, the modified oblique triangular neurovascular island flap is routinely used for patients who underwent fingertip amputation with a retained nail bed. These modifications may aid in preventing the development of hooked nail deformity and creating a round pulp contour without the need for fixation, composite grafts, or distant soft tissue transfer.
Immune Checkpoint Inhibitor-induced Bilateral Vestibulopathy
Authors: Koch Elias A.T. , Nickel Florian T. , Heinzerling Lucie , Schulz Yvonne K. , Berking Carola , Erdmann Michael
Published: December 2020

Checkpoint inhibitors (CPI), such as anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen-4antibodies cause serious, rarely fatal immune-related adverse events (irAE) potentially in all organ systems. Neurological immune-related adverse events occur in 1%–5% of patients on CPI therapy and may present with dramatic clinical symptoms of the sensory organs. After exclusion of other causes, a high-dose treatment with corticosteroids is crucial for clinical outcome with lower risk of sequelae. We present a severe case of CPI-related ongoing and most likely irreversible bilateral vestibular affection. A 59-year-old male melanoma patient with brain metastasis undergoing immunotherapy with anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death-1 antibodies developed severe debilitating rotatory vertigo. Bilateral vestibulopathy was diagnosed as a result of the CPI therapy after a thorough analysis including magnetic resonance imaging, laboratory tests of blood and cerebrospinal fluid as well as neurological and otorhinolaryngology examinations. The vertigo improved slightly during a 10-day course of steroid therapy and intensive balance training but did not resolve completely.
The Impact of Biopsy Tool Choice and Rapid On-Site Evaluation on Diagnostic Accuracy for Malignant Lesions in the Prospective
Authors: Gildea Thomas R. , Folch Erik E. , Khandhar Sandeep J. , Pritchett Michael A. , LeMense Gregory P. , Linden Philip A. , Arenberg Douglas A. , Rickman Otis B. , Mahajan Amit K. , Singh Jaspal , Cicenia Joseph , Mehta Atul C. , Lin Haiying , Mattingley Jennifer S.
Published: December 2020

Background:

The diagnostic yield of electromagnetic navigation bronchoscopy (ENB) is impacted by biopsy tool strategy and rapid on-site evaluation (ROSE) use. This analysis evaluates usage patterns, accuracy, and safety of tool strategy and ROSE in a multicenter study.

Methods:

NAVIGATE (NCT02410837) evaluates ENB using the superDimension navigation system (versions 6.3 to 7.1). The 1-year analysis included 1215 prospectively enrolled subjects at 29 United States sites. Included herein are 416 subjects who underwent ENB-aided biopsy of a single lung lesion positive for malignancy at 1 year. Use of a restricted number of tools (only biopsy forceps, standard cytology brush, and/or bronchoalveolar lavage) was compared with an extensive multimodal strategy (biopsy forceps, cytology brush, aspirating needle, triple needle cytology brush, needle-tipped cytology brush, core biopsy system, and bronchoalveolar lavage).

Results:

Of malignant cases, 86.8% (361/416) of true positive diagnoses were obtained using extensive multimodal strategies. ROSE was used in 300/416 cases. The finding of malignancy by ROSE reduced the total number of tools used. A malignant ROSE call was obtained in 71% (212/300), most (88.7%; 188/212) by the first tool used (49.5% with aspirating needle, 20.2% with cytology brush, 17.0% with forceps). True positive rates were highest for the biopsy forceps (86.9%) and aspirating needle (86.6%). Use of extensive tool strategies did not increase the rates of pneumothorax (5.5% restricted, 2.8% extensive) or bronchopulmonary hemorrhage (3.6% restricted, 1.1% extensive).

Conclusion:

These results suggest that extensive biopsy tool strategies, including the aspirating needle, may provide higher true positive rates for detecting lung cancer without increasing complications.
Impact of a Dedicated Education Unit Experience on Critical Thinking Development in Nursing Students
Authors: Bittner Nancy Phoenix , Campbell Elizabeth , Gunning Thomas
Published: December 2020

Aim

The purpose of this study was to identify the impact of the dedicated education unit (DEU) on nursing students' critical thinking ability.

Background

The DEU is an innovative approach to clinical education, which uses clinical nurses with expert practice consistently in a competency-based experience.

Method

Participants (intervention and control groups) completed the Nursing Executive Center's Critical Thinking Diagnostic Assessment tool before and after clinical experience.

Results

Participants included 243 students with 179 non-DEU and 64 DEU students. There were significant increases in total pretest and posttest score means (P < .05) for the DEU (intervention) group. A significant change (P < .0001) was seen in critical thinking scores by category for both groups and in the intervention group on pretest and posttest scores, even after controlling for pretest scores (P < .0001).

Conclusions

Results support the efficacy of the DEU model in developing critical thinking. Prior DEU studies have focused on implementation and satisfaction with the model.
Dedifferentiated and Undifferentiated Melanomas
Authors: Agaimy Abbas , Stoehr Robert , Hornung Annkathrin , Popp Judith , Erdmann Michael , Heinzerling Lucie , Hartmann Arndt
Published: December 2020

Dedifferentiated melanoma (DM) and undifferentiated melanoma (UM) is defined as a primary or metastatic melanoma showing transition between conventional and undifferentiated components (DM) or lacking histologic and immunophenotypic features of melanoma altogether (UM). The latter is impossible to verify as melanoma by conventional diagnostic tools alone. We herein describe our experience with 35 unpublished cases to expand on their morphologic, phenotypic, and genotypic spectrum, along with a review of 50 previously reported cases (total: 85) to establish the diagnostic criteria. By definition, the dedifferentiated/undifferentiated component lacked expression of 5 routinely used melanoma markers (S100, SOX10, Melan-A, HMB45, Pan-melanoma). Initial diagnoses (known in 66 cases) were undifferentiated/unclassified pleomorphic sarcoma (n=30), unclassified epithelioid malignancy (n=7), pleomorphic rhabdomyosarcoma (n=5), other specific sarcoma types (n=6), poorly differentiated carcinoma (n=2), collision tumor (n=2), atypical fibroxanthoma (n=2), and reactive osteochondromatous lesion (n=1). In only 11 cases (16.6%) was a diagnosis of melanoma considered. Three main categories were identified: The largest group (n=56) comprised patients with a history of verified previous melanoma who presented with metastatic DM or UM. Axillary or inguinal lymph nodes, soft tissue, bone, and lung were mainly affected. A melanoma-compatible mutation was detected in 35 of 48 (73%) evaluable cases: BRAF (n=20; 40.8%), and NRAS (n=15; 30.6%). The second group (n=15) had clinicopathologic features similar to group 1, but a melanoma history was lacking. Axillary lymph nodes (n=6) was the major site in this group followed by the lung, soft tissue, and multiple site involvement. For this group, NRAS mutation was much more frequent (n=9; 60%) than BRAF (n=3; 20%) and NF1 (n=1; 6.6%). The third category (n=14) comprised primary DM (12) or UM (2). A melanoma-compatible mutation was detected in only 7 cases: BRAF (n=2), NF1 (n=2), NRAS (n=2), and KIT exon 11 (n=1). This extended follow-up study highlights the high phenotypic plasticity of DM/UM and indicates significant underrecognition of this aggressive disease among general surgical pathologists. The major clues to the diagnosis of DM and UM are: (1) presence of minimal differentiated clone in DM, (2) earlier history of melanoma, (3) undifferentiated histology that does not fit any defined entity, (4) locations at sites that are unusual for undifferentiated/unclassified pleomorphic sarcoma (axilla, inguinal, neck, digestive system, etc.), (5) unusual multifocal disease typical of melanoma spread, (6) detection of a melanoma-compatible gene mutation, and (7) absence of another genuine primary (eg, anaplastic carcinoma) in other organs.
Content Evidence for Validity of Time-to-Task Initiation
Authors: Nichols Blake E. , McMichael Ali B. V. , Ambardekar Aditee P.
Published: December 2020

Introduction

Educators require validated tools to assess learner competency in simulation-based mastery learning. We previously created a simulation to incorporate crisis resource management skills after a needs assessment of our pediatric residency program. We present the development of and content evidence for validity of a task list with time-to-task initiation designed to aid in rapid cycle deliberate practice (RCDP) debriefing and assessment of pediatrics resident learners.

Methods

Five board-certified pediatricians developed the initial task list with 30 tasks. We used the Delphi technique to seek content evidence for validity of the initial task list using 17 board-certified pediatricians at 7 institutions across the United States. After finalizing the task list, we video recorded 3 pediatric experts performing the tasks in a simulation. We then used the Delphi technique to establish and to attain agreement on time-to-task initiation. We calculated Cronbach α coefficient to measure internal consistency of the expert responses. After finalizing the task list, we divided it into 3 stages with 5 separate cycles per stage to direct the educator in performance of RCDP debriefing.

Results

The group reached 80% agreement after 2 Delphi rounds with a Cronbach α coefficient of 0.95. The resultant list included 25 tasks. The group subsequently achieved 80% agreement on the time-to-task initiation in 2 Delphi rounds.

Conclusions

We present content evidence for validity of a task list with associated time-to-task initiation for a simulation scenario that incorporates crisis resource management skills and is designed to aid educators in RCDP debriefing. This task list may decrease intereducator inconsistencies in delivery of RCDP for a common pediatric resuscitation scenario.
High Rate of Positive Circumferential Resection Margin in Colon Cancer
Authors: Healy Mark A. , Peacock Oliver , Hu Chung-Yuan , Bednarski Brian K. , Tillman Matthew M. , Messick Craig , Kaur Harmeet , Chang George J.
Published: December 2020

Objective:

To identify rates of positive circumferential resection margin (CRM) for colon cancer surgery in the US.

Summary Background Data:

CRM is one of the most important determinants of local control in colorectal cancers. The extent to which CRM involvement exists after colon cancer surgery is unknown.

Methods:

Colon cancer cases with resection 2010 to 2015 were identified from the National Cancer Data Base. Adjusting for patient and tumor characteristics, comparisons were made between cases with CRM > 1 mm (negative margin) and those with margin involved with tumor or ≤ 1 mm (positive margin, CRM+). Hospital-level analysis was performed, examining observed-to-expected CRM+ rates.

Results:

In total, 170,022 cases were identified: 150,291 CRM- and 19,731 CRM+ (11.6%). Pathologic T-category was the greatest predictor of CRM+, with higher rates in pT4(25.8%), pT4A(24.7%), and pT4B(31.5%) versus pT1(4.5%), pT2(6.3%) and pT3 (10.9%, P < 0.001). Within pT4 patients, predictors of CRM+ included signet-ring histology (38.1% vs 26.7% nonmucinous, and 26.9% mucinous adenocarcinoma, P < 0.001), removing < 12 lymph nodes (36.5% vs 26.1% >12, P < 0.001), community facilities (32.7%) versus academic/research (23.6%, P < 0.001), year (30.1% 2010 vs 22.6% 2015, P < 0.001), and hospital volume (24.5% highest quartile vs 32.7% lowest, P < 0.001). Across 1288 hospitals, observed-to-expected ratios for CRM+ ranged from 0 to 7.899; 429 facilities had higher than expected rates.

Conclusions:

Overall rate of CRM+ in US colon cancer cases is high. Variation exists across hospitals, with higher than expected rates in many facilities. Although biology is a major influencing factor, CRM+ rates represent an area for multidisciplinary improvement in quality of colon cancer care.
Adaptive immunity to SARS-CoV-2 in cancer patients: The CAPTURE study
Authors: Fendler Annika , Au Lewis , Boos Laura Amanda , Byrne Fiona , Shepherd Scott T.C. , Shum Ben , Gerard Camille L. , Ward Barry , Xie Wenyi , Cerrone Maddalena , Cornish Georgina H. , Pule Martin , Mekkaoui Leila , Ng Kevin W. , Stone Richard , Gomes Camila , Flynn Helen R. , Agua-Doce Ana , Hobson Phillip , Caidan Simon , Howell Mike , Goldstone Robert , Gavrielides Mike , Nye Emma , Snijders Bram , Macrae James , Nicod Jerome , Hayday Adrian , Gronthoud Firza , Messiou Christina , Cunningham David , Chau Ian , Starling Naureen , Turner Nicholas , Rusby Jennifer , Welsh Liam , van As Nicholas , Jones Robin , Droney Joanne , Banerjee Susana , Tatham Kate , Jhanji Shaman , O’Brien Mary , Curtis Olivia , Harrington Kevin , Bhide Shreerang , Slattery Tim , Khan Yasir , Tippu Zayd , Leslie Isla , Gennatas Spyridon , Okines Alicia , Reid Alison , Young Kate , Furness Andrew , Pickering Lisa , Ghandi Sonia , Gamblin Steve , Swanton Charles , Nicholson Emma , Kumar Sacheen , Yousaf Nadia , Wilkinson Katalin , Swerdlow Anthony , Harvey Ruth , Kassiotis George , Wilkinson Robert , Larkin James , Turajlic Samra
Published: December 2020

There is a pressing need to characterise the nature, extent and duration of immune response to SARS-CoV-2 in cancer patients and inform risk-reduction strategies and preserve cancer outcomes. CAPTURE is a prospective, longitudinal cohort study of cancer patients and healthcare workers (HCWs) integrating longitudinal immune profiling and clinical annotation. We evaluated 529 blood samples and 1051 oronasopharyngeal swabs from 144 cancer patients and 73 HCWs and correlated with >200 clinical variables. In patients with solid cancers and HCWs, S1-reactive and neutralising antibodies to SARS-CoV-2 were detectable five months post-infection. SARS-CoV-2-specific T-cell responses were detected, and CD4+T-cell responses correlated with S1 antibody levels. Patients with haematological malignancies had impaired but partially compensated immune responses. Overall, cancer stage, disease status, and therapies did not correlate with immune responses. These findings have implications for understanding individual risks and potential effectiveness of SARS-CoV-2 vaccination in the cancer population.
Discovery of Cyclic Peptide Ligands to the SARS-CoV-2 Spike Protein using mRNA Display
Authors: Norman Alexander , Franck Charlotte , Christie Mary , Hawkins Paige M. E. , Patel Karishma , Ashhurst Anneliese S. , Aggarwal Anupriya , Low Jason K. K. , Siddiquee Rezwan , Ashley Caroline L. , Steain Megan , Triccas James A. , Turville Stuart , Mackay Joel P. , Passioura Toby , Payne Richard J.
Published: December 2020

The COVID-19 pandemic, caused by SARS-CoV-2, has led to substantial morbidity, mortality and disruption globally. Cellular entry of SARS-CoV-2 is mediated by the viral spike protein and affinity ligands to this surface protein have the potential for applications as antivirals and diagnostic reagents. Here, we describe the affinity selection of cyclic peptide ligands to the SARS-CoV-2 spike protein receptor binding domain (RBD) from three distinct libraries (in excess of a trillion molecules each) by mRNA display. We identified six high affinity molecules with dissociation constants (KD) in the nanomolar range (15-550 nM) to the RBD. The highest affinity ligand could be used as an affinity reagent to detect spike protein in solution by ELISA, and the co-crystal structure of this molecule bound to the RBD demonstrated that it binds to a cryptic binding site, displacing a β-strand near the C-terminus. Our findings provide key mechanistic insight into the binding of peptide ligands to the SARS-CoV-2 spike RBD and the ligands discovered in this work may find future use as reagents for diagnostic applications.
VarSAn: Associating pathways with a set of genomic variants using network analysis
Authors: Xie Xiaoman , Kendzior Matthew C. , Ge Xiyu , Mainzer Liudmila S. , Sinha Saurabh
Published: December 2020

There is a pressing need today to mechanistically interpret sets of genomic variants associated with diseases. Here we present a tool called ‘VarSAn’ that uses a network analysis algorithm to identify pathways relevant to a given set of variants. VarSAn analyzes a configurable network whose nodes represent variants, genes and pathways, using a Random Walk with Restarts algorithm to rank pathways for relevance to the given variants, and reports p-values for pathway relevance. It treats non-coding and coding variants differently, properly accounts for the number of pathways impacted by each variant and identifies relevant pathways even if many variants do not directly impact genes of the pathway. We use VarSAn to identify pathways relevant to variants related to cancer and several other diseases, as well as drug response variation. We find VarSAn’s pathway ranking to be complementary to the standard approach of enrichment tests on genes related to the query set. We adopt a novel benchmarking strategy to quantify its advantage over this baseline approach. Finally, we use VarSAn to discover key pathways, including the VEGFA-VEGFR2 pathway, related to de novo variants in patients of Hypoplastic Left Heart Syndrome, a rare and severe congenital heart defect.
Microcircuit synchronization and heavy tailed synaptic weight distribution in preBötzinger Complex contribute to generation of breathing rhythm
Authors: Slepukhin Valentin M. , Ashhad Sufyan , Feldman Jack L. , Levine Alex J.
Published: December 2020

The preBötzinger Complex, the mammalian inspiratory rhythm generator, encodes inspiratory time as motor pattern. Spike synchronization throughout this sparsely connected network generates inspiratory bursts albeit with variable latencies after preinspiratory activity onset in each breathing cycle. Using preBötC rhythmogenic microcircuit minimal models, we examined the variability in probability and latency to burst, mimicking experiments. Among various physiologically plausible graphs of 1000 point neurons with experimentally determined neuronal and synaptic parameters, directed Erdős-Rényi graphs best captured the experimentally observed dynamics. Mechanistically, preBötC (de)synchronization and oscillatory dynamics are regulated by the efferent connectivity of spiking neurons that gates the amplification of modest preinspiratory activity through input convergence. Furthermore, to replicate experiments, a lognormal distribution of synaptic weights was necessary to augment the efficacy of convergent coincident inputs. These mechanisms enable exceptionally robust yet flexible preBötC attractor dynamics that, we postulate, represent universal temporal-processing and decision-making computational motifs throughout the brain.
Brucella oviscysteine biosynthesis contributes to peroxide stress survival and fitness in the intracellular niche
Authors: Varesio Lydia M. , Fiebig Aretha , Crosson Sean
Published: December 2020

Brucella ovisis an ovine intracellular pathogen with tropism for the male genital tract. To establish and maintain infection,B. ovismust survive stressful conditions inside host cells, including low pH, nutrient limitation, and reactive oxygen species. These same conditions are often encountered in axenic cultures during stationary phase. Studies of stationary phase may thus inform understanding ofBrucellainfection biology, yet the genes and pathways that are important inBrucellastationary phase physiology remain poorly defined. We measured fitness of a barcoded pool ofB. ovisTn-himarmutants as a function of growth phase and identifiedcysEas a determinant of fitness in stationary phase. CysE catalyzes the first step in cysteine biosynthesis from serine, and we provide genetic evidence that two related enzymes, CysK1 and CysK2, function redundantly to catalyze cysteine synthesis at steps downstream of CysE. Deleting eithercysE(ΔcysE) or bothcysK1andcysK2(ΔcysK1ΔcysK2) results in premature entry into stationary phase, reduced culture yield and sensitivity to exogenous hydrogen peroxide. These phenotypes can be chemically complemented by cysteine or glutathione. ΔcysEand ΔcysK1ΔcysK2strains have no defect in host cell entryin vitrobut have significantly diminished intracellular fitness between 2 and 24 hours post infection. Our study has uncovered unexpected redundancy at the CysK step of cysteine biosynthesis inB. ovis, and demonstrates that cysteine anabolism is a determinant of peroxide stress survival and fitness in the intracellular niche.
Functional architecture of the pancreatic islets reveals first responder cells which drive the first-phase [Ca2+] response
Authors: Kravets Vira , Dwulet JaeAnn M. , Schleicher Wolfgang E. , Hodson David J. , Davis Anna M. , Pyle Laura , Piscopio Robert A. , Sticco-Ivins Maura , Benninger Richard K.P.
Published: December 2020

Insulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine ‘first responder’ cells, defined by the earliest [Ca2+] response during first-phase [Ca2+] elevation, distinct from previously identified “hub” and “leader” cells. First responder cells showed characteristics of high membrane excitability and lower electrical coupling to their neighbors. The first-phase response time of β-cells in the islet was spatially organized, dependent on the cell’s distance to the first responder cell, and consistent over time up to ∼24 h. When first responder cells were laser ablated, the first-phase [Ca2+] was slowed down, diminished, and discoordinated compared to random cell ablation. Cells that were next earliest to respond often took over the role of the first responder upon ablation. In summary, we discover and characterize a distinct first responder β-cell state, critical for the islet first-phase response to glucose.