bluuebunny/crossref_metadata_2025 huggingface dataset:
A Unified Theoretical Framework of Learning Theories to Inform and Guide Public Health Continuing Medical Education Research and Practice
Authors: Roux Thomas L. , Heinen Mirjam M. , Murphy Susan P. , Buggy Conor J.
Published: March 2021

Continuing medical education (CME) emerged at the start of the 20th century as a means of maintaining clinical competence among health care practitioners. However, evidence indicates that CME is often poorly developed and inappropriately used. Consequently, there has been increasing interest in the literature in evaluating wider contexts at play in CME development and delivery. In this article, the authors present a unified theoretical framework, grounded in learning theories, to explore the role of contextual factors in public health CME for health care practitioners. Discussion with pedagogical experts together with a narrative review of learning theories within medical and social science literature informed the framework's development. The need to consider sociocultural theories of learning within medical education restricted suitable theories to those that recognized contexts beyond the individual learner; adopted a systems approach to evaluate interactions between contexts and learner; and considered learning as more than mere acquisition of knowledge. Through a process of rigorous critical analysis, two theoretical models emerged as contextually appropriate: Biggs principle of constructive alignment and Bronfenbrenner bioecological model of human development. Biggs principle offers theoretical clarity surrounding interactive factors that encourage lifelong learning, whereas the Bronfenbrenner model expands on these factor's roles across multiple system levels. The authors explore how unification into a single framework complements each model while elaborating on its fundamental and practical applications. The unified theoretical framework presented in this article addresses the limitations of isolated frameworks and allows for the exploration of the applicability of wider learning theories in CME research.
INVESTIGATING MICROANGIOPATHY USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH SUSAC SYNDROME
Authors: Wirth Magdalena A. , Khan Haaris M. , Chan Jillian , Carruthers Robert , Lo Julian , Sarunic Marinko V. , Navajas Eduardo V. , Sheldon Claire A.
Published: March 2021

Purpose:

To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes.

Methods:

We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). Images of the fovea were taken using an optical coherence tomography angiography system. Analysis included vessel density, fractal dimension, vessel diameter, and measurements of the foveal avascular zone (area, eccentricity, acircularity index, and axis ratio) in deep and superficial retinal layers.

Results:

Skeleton density and inner ring vessel density were significantly lower in patients with SuS (skeleton density: Susac 0.11 ± 0.01 vs. controls 0.12 ± 0.01, P = 0.027. VD: SuS 0.39 ± 0.04 vs. controls 0.42 ± 0.02, P = 0.041). Eccentricity and axis ratio were significantly higher in patients with SuS (EC: Susac 0.61 ± 0.11, controls 0.51 ± 0.10, P = 0.003; axis ratio: Susac 1.57 ± 0.28, controls 1.39 ± 0.11, P = 0.005). SuS eyes (affected and unaffected) had poorer outcomes of the remaining vascular parameters compared with controls (P > 0.05).

Conclusion:

Optical coherence tomography angiography identified chronic microvascular changes in the eyes of patients with chronic SuS. Even clinically unaffected SuS eyes showed poorer vascular parameters. Although further research is needed, this noninvasive imaging modality seems to have the potential to serve as a valuable additive diagnostic tool.
Honeycomb Epithelial Edema Associated With Rho Kinase Inhibition: A Case Series and Review of the Literature
Authors: Lyons Lance J. , Wu Kristi Y. , Baratz Keith H. , Sit Arthur J.
Published: March 2021

The Rho kinase inhibitor netarsudil is a recently approved therapeutic option for the management of increased intraocular pressure in the United States. Although phase 3 clinical trials noted corneal changes related to the medication—namely, nonvisually-significant corneal verticillata—descriptions of a unique form of cystic epithelial edema began to surface as netarsudil (and its sister drug ripasudil, approved in Japan) gained widespread use. This series adds 3 new cases and reviews the current literature on this unique side effect.
Rose Bengal Photodynamic Antimicrobial Therapy: A Pilot Safety Study
Authors: Martinez Jaime D. , Arrieta Esdras , Naranjo Andrea , Monsalve Pedro , Mintz Keenan J. , Peterson Jeffrey , Arboleda Alejandro , Durkee Heather , Aguilar Mariela C. , Pelaez Daniel , Dubovy Sander R. , Miller Darlene , Leblanc Roger , Amescua Guillermo , Parel Jean-Marie
Published: March 2021

Purpose:

To evaluate the in vivo corneal changes after Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) treatment in New Zealand White rabbits.

Methods:

Sixteen rabbits were divided into 5 groups. All groups underwent deepithelialization of an 8 mm diameter area in the central cornea. Group 1: balanced salt solution drops only, group 2: 0.2% RB only, group 3: green light exposure (525 nm, 5.4 J/cm2) only, group 4: 0.1% RB-PDAT, and group 5: 0.1% RB-PDAT. All rabbits were followed clinically. Group 5 rabbits were followed using anterior segment optical coherence tomography (AS-OCT) and clinically. On day 35 after initial treatment, 1 rabbit from group 5 was re-exposed to green light (5.4 J/cm2) to evaluate reactivation of the remaining RB dye, and terminal deoxynucleotyl transferase–mediated UTP-biotin-nick-end labeling assay was performed on corneal cryosections.

Results:

Complete reepithelization was observed, and corneas remained clear after treatment in all groups. In group 5, AS-OCT revealed a cross-linking demarcation line. AS-OCT showed RB fluorescence and collagen cross-linking in all treated eyes of group 5 animals after 5 weeks of treatment. Photobleached RB retention in the corneal stroma was corroborated by fluorescence confocal microscopy on frozen sections. There was no evidence of a sustained cytotoxic effect through terminal deoxynucleotyl transferase-mediated UTP-biotin-nick-end labeling at 5 weeks.

Conclusions:

RB-PDAT with 0.1% RB is a safe procedure. There was no difference clinically and on histopathology compared with control groups. In eyes where RB dye is retained in the corneal stroma after 1 month of treatment, oxidative stress is not evidenced at long term.
Transbronchial Forceps Biopsy in the Intensive Care Unit
Authors: Helgeson Scott A. , Imam Jaafer S. , Burnside Rebecca C. , Fernandez-Bussy Sebastian , Brigham Tara J. , Patel Neal M.
Published: March 2021

Background:

A transbronchial forceps lung biopsy performed in mechanically ventilated patients with respiratory failure of unknown etiology has significant uncertainty of diagnostic yield and safety along with sparse literature. This study investigated the complication rate of transbronchial biopsies in mechanically ventilated patients in the intensive care unit and its ability to obtain a diagnosis and change current therapy.

Methods:

PubMed, Ovid MEDLINE, and Ovid Cochrane Central Register of Controlled Trials databases were systematically searched for all publications of transbronchial lung biopsies in mechanically ventilated patients. We pooled the results of individual studies using random-effects meta-analysis models to achieve the summary proportions.

Results:

Of the identified 9 observational studies with a total of 232 patients undergoing a transbronchial biopsy, complications occurred in 67 patients [25.2%; 95% confidence interval (CI), 11.5%-42.0%; I
2=70.0%]. Pneumothorax occurred in 24 patients (9.5%; 95% CI, 4.5%-16.2%; I
2=15.9%) and bleeding in 18 patients (8.9%; 95% CI, 4.1%-15.3%; I
2=0%). A diagnosis was given in 146 patients (62.9%; 95% CI, 56.0%-69.1%; I
2=74.6%), with 103 of 210 patients (49.0%; 95% CI, 44.6%-55.1%; I
2=74.9%) having a change in treatment.

Conclusion:

The results of this meta-analysis suggest that a transbronchial forceps biopsy when performed in mechanically ventilated patients with respiratory failure of unclear etiology had a moderate complication rate. These biopsies resulted in varied diagnoses with a high rate of management change. Randomized controlled trials are necessary to identify the ideal patients to perform a transbronchial forceps biopsy on in the intensive care unit.
Mesenchymal stem cell therapy for liver disease: current status and future perspectives
Authors: Eom Young Woo , Yoon Yongdae , Baik Soon Koo
Published: March 2021

Purpose of review

Liver transplantation is the gold standard for the treatment of end-stage liver disease. However, a shortage of donor organs, high cost, and surgical complications limit the use of this treatment. Cellular therapies using hepatocytes, hematopoietic stem cells, bone marrow mononuclear cells, and mesenchymal stem cells (MSCs) are being investigated as alternative treatments to liver transplantation. The purpose of this review is to describe studies using MSC transplantation for liver diseases based on the reported literature and to discuss prospective research designed to improve the efficacy of MSC therapy.

Recent findings

MSCs have several properties that show potential to regenerate injured tissues or organs, such as homing, transdifferentiation, immunosuppression, and cellular protective capacity. Additionally, MSCs can be noninvasively isolated from various tissues and expanded ex vivo in sufficient numbers for clinical evaluation.

Currently, there is no approved MSC therapy for the treatment of liver disease. However, MSC therapy is considered a promising alternative treatment for end-stage liver diseases and is reported to improve liver function safely with no side effects. Further robust preclinical and clinical studies will be needed to improve the therapeutic efficacy of MSC transplantation.
Comparing the responsiveness of a generic and a musculoskeletal specific functional outcome measure in orthopaedic patients with operative fixation of pelvic ring, acetabulum, or tibia fractures: a comparison between single injury and multiply injured patients
Authors: Sepehri Aresh , Sleat Graham K.J. , O’Brien Peter J. , Broekhuyse Henry M. , Guy Pierre , Lefaivre Kelly A.
Published: March 2021

Objectives:

This study compares the responsiveness, or the ability to detect clinical change in a disease, between the generic Short Form-36 (SF-36) and musculoskeletal specific Short Musculoskeletal Functional Assessment (SMFA) patient-reported outcome measures (PROMs) in the orthopaedic trauma population. Stratified analysis was performed to compare whether responsiveness differs between patients with single or multiple orthopaedic injuries.

Design:

Prospective case series.

Setting:

Level 1 Trauma Center.

Patients:

A total of 659 patients with orthopaedic trauma injuries to the pelvis, acetabulum, or tibia were included for analysis. There were 485 patients with a single isolated injury and 174 patients with multiple orthopaedic injuries.

Intervention:

None.

Main Outcome Measurements:

Responsiveness was calculated through the standard response mean (SRM), the proportion meeting a minimal clinically important difference, and floor and ceiling effects.

Results:

Between baseline and 6 months the magnitude of the SRM for SF-36 was consistently greater than that of SMFA in patients with single (P < .01) and multiple injuries (P < .01). Between 6 and 12 months, there were no differences in SRM across all cohorts. The proportion of patients who achieved minimal clinically important difference was consistently higher when assessed with SF-36 compared with SMFA between baseline and 6 months (81.8% vs 68.1%, P < .0001) and between 6 and 12 months (63.3% vs 55.4%, P = .01).

A ceiling effect was only observed at baseline for the SMFA with 16.6% of patients achieving the maximal level of functioning detectable. No floor effects were seen in either PROM.

Conclusion:

This study demonstrates that SF-36 has superior responsiveness versus SMFA in both polytrauma and isolated injury patients and supports the collection of SF-36 as the primary PROM in prospective orthopaedic trauma studies irrespective of whether the patient has an isolated injury or multiple injuries.
Historical Advancements and Evolution in Understanding Human Anatomy and Pathology: The Contribution of the Middle Ages
Authors: Roguin Alon L. , Roguin Ariel , Roguin Nathan
Published: March 2021

Dissections and autopsies are critical for understanding human anatomy, pathology, and uncovering mechanisms of disease. This review presents an historical journey from ancient times until the late Middle Ages. The major steps and developments are summarized with key figures and events presented.
ALK Rearrangements Characterize 2 Distinct Types of Salivary Gland Carcinomas
Authors: Agaimy Abbas , Baněčková Martina , Ihrler Stephan , Mueller Sarina K. , Franchi Alessandro , Hartmann Arndt , Stoehr Robert , Skálová Alena
Published: March 2021

The majority of salivary gland carcinomas are characterized by recurrent gene fusions that proved highly valuable diagnostically, but only rarely of therapeutic impact. Most of these fusion-positive carcinomas belong to the low-grade or intermediate-grade biological category. To date, only 5 cases of salivary gland carcinomas carrying an oncogenic ALK fusion have been reported in 4 recent studies, but their phenotypic spectrum and their nosological classification remain uncharacterized. We herein describe in detail the clinicopathologic and molecular features of 4 ALK–fusion-positive salivary carcinomas and review previously reported cases to assess if they could be classified into a defined World Health Organization (WHO) category. Patients were 3 men and 1 woman aged from 67 to 79 years (median: 70 y). All tumors originated in the parotid gland. Their size ranged from 1.1 to 3 cm (mean, 2 cm). Three tumors were de novo high-grade salivary duct carcinomas (SDCs) and 1 was a low-grade intercalated-type intraductal carcinoma. Histologically, high-grade tumors were predominantly solid, composed of intimately admixed basal (CK5+, androgen−) and luminal (CK5−, androgen+) components. The remarkable basal component showed squamoid basophilic pattern imparting an adenosquamous-like appearance in all cases. Conventional apocrine intraductal high-grade carcinoma was noted in 1 case. Prominent intraductal growth of the solid basal component (highlighted by p63 staining) was seen in all cases. The tumor cells expressed CK7 (3/3), mammaglobin (3/3, 1 focal), GATA3 (3/3, 1 focal), variably CK5 (3/3), and focally the androgen receptor (1/3), but lacked expression of HER2/neu, SOX10, MUC4, TTF1, S100, and Napsin A. The low-grade tumor showed classic histologic and immunophenotypic features of intercalated-type noninvasive intraductal carcinoma. Molecular profiling showed rearrangements involving exon 20 of ALK in all cases, confirmed by ALK immunohistochemistry (IHC and FISH). The fusion partner was EML4 (n=2) and STRN (n=1) in high-grade tumors and EML4 in the intraductal carcinoma. Two patients with high-grade tumors developed progressive disease (1 died at 9 mo; 1 alive under palliative therapy at 5 mo). This series and a review of 5 published cases indicate that ALK rearrangements characterize 2 distinct subsets of salivary gland carcinomas in the spectrum of high-grade androgen-poor, basal-like SDC (total reported: 5 cases) and low-grade intercalated-type intraductal carcinomas (4 cases). Given the therapeutic relevance of ALK fusions, inclusion of ALK IHC in any atypical-looking or androgen-poor SDC and in high-grade adenocarcinoma-not otherwise specified is recommended. Absence of aberrant ALK expression in genetically characterized secretory (n=15) and intraductal (n=9) carcinomas lacking ALK fusions underlines the value of ALK IHC as a diagnostic screening method for identifying potential cases.
Immunohistochemical Characterization of 120 Testicular Sex Cord-Stromal Tumors With an Emphasis on the Diagnostic Utility of SOX9, FOXL2, and SF-1
Authors: Lau Hubert D. , Kao Chia-Sui , Williamson Sean R. , Cheng Liang , Ulbright Thomas M. , Idrees Muhammad T.
Published: March 2021

Sex cord-stromal tumors (SCSTs) account for the second most common category of testicular neoplasms and include several entities that may show overlapping morphologies and present diagnostic challenges. We analyzed a cohort of 120 testicular SCSTs and investigated the diagnostic utility of SRY-box transcription factor 9 (SOX9), forkhead box protein L2 (FOXL2), and steroidogenic factor 1 (SF-1) immunohistochemical stains. The results were compared with the more commonly used SCST markers, inhibin α, calretinin, and Wilms’ tumor 1 (WT1). SF-1 was overall the most sensitive stain (91%), followed by inhibin α (70%), calretinin (52%), FOXL2 (50%), SOX9 (47%), and WT1 (37%), but sensitivities varied by tumor type. SOX9 and calretinin were more commonly positive in sex cord elements versus stromal elements (62% vs. 27% and 47% vs. 9%, respectively), whereas FOXL2 was more commonly positive in stromal elements versus sex cord elements (100% vs. 55%) when excluding Leydig cell tumors from the stromal category. Although no individual stain was diagnostically specific, some immunophenotypic patterns were noted that may help in the subclassification of SCSTs. We conclude that SOX9, FOXL2, and SF-1 are useful immunohistochemical stains for confirming sex cord-stromal differentiation in testicular tumors and provide increased sensitivity as well as additional diagnostic information, especially when combined with the more commonly used inhibin α, calretinin, and WT1 immunostains. Although morphology is paramount for subclassification of SCSTs, knowledge of certain immunohistochemical patterns may be helpful for diagnostically challenging cases.
JAK2 Rearrangements Are a Recurrent Alteration in CD30+ Systemic T-Cell Lymphomas With Anaplastic Morphology
Authors: Fitzpatrick Megan J. , Massoth Lucas R. , Marcus Chelsea , Vergilio Jo-Anne , Severson Eric , Duncan Daniel , Ramkissoon Shakti H. , Hasserjian Robert P. , Kim Annette S. , Sohani Aliyah R. , Williams Erik A. , Nardi Valentina
Published: March 2021

Peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare mature T-cell neoplasms. While some PTCL subtypes are well-characterized by histology, immunophenotype, and recurrent molecular alterations, others remain incompletely defined. In particular, the distinction between CD30+ PTCL, not otherwise specified and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma can be subject to disagreement. We describe a series of 6 JAK2 rearrangements occurring in a cohort of 97 CD30+ ALK− PTCL (6%), assembled after identifying an index case of a novel PABPC1-JAK2 fusion in a case of ALK− anaplastic large cell lymphoma with unusual classic Hodgkin lymphoma (CHL)-like features. Fusions were identified using a comprehensive next-generation sequencing based assay performed between 2013 and 2020. Five of 6 cases (83%) showed JAK2 rearrangements with 4 novel partners: TFG, PABPC1, ILF3, and MAP7, and 1 case demonstrated a previously described PCM1-JAK2 fusion. By morphology, all cases showed anaplastic large cells and multinucleated Reed-Sternberg–like cells within a polymorphous inflammatory background with frequent eosinophilia reminiscent of CHL. By immunohistochemistry, atypical large cells expressed CD30 with coexpression of at least 1 T-cell marker, aberrant loss of at least 1 T-cell marker and, in 4 of 5 cases stained (80%), unusual CD15 coexpression. These findings suggest that a subset of CD30+ ALK− systemic PTCL with anaplastic morphology carry JAK2 rearrangements, some of which appear to show CHL-like morphologic features. The presence of JAK2 rearrangements in cases of CD30+ PTCL augments current classification and may provide a therapeutic target via JAK2 inhibition.
Liver Pathology, Including MOC31 Immunohistochemistry, in Congenital Tufting Enteropathy
Authors: Chen Sonja , Goldsmith Jeffrey D. , Fawaz Rima , Al-Ibraheemi Alyaa , Perez-Atayde Antonio R. , Vargas Sara O.
Published: March 2021

Congenital tufting enteropathy (CTE) is a rare heritable cause of intractable diarrhea due to EPCAM mutation. Pathologic findings include intestinal villous atrophy, tufted discohesive tear-drop-shaped epithelium, and a normal brush border. In affected patients, absent intestinal epithelial cell adhesion molecule (EpCAM) expression results in loss of MOC31 immunostaining. CTE liver pathology has not yet been described. We identified CTE patients with liver biopsies and reviewed clinicopathologic material including MOC31 immunohistochemistry. Three CTE patients had 4 liver core biopsies (at ages 1, 5, 7, and 16 y), 2 for preintestinal transplant evaluation, and 2 (from a single patient) for pretreatment assessment of chronic hepatitis C; all had received parenteral nutrition (PN). All samples showed loss of biliary epithelial polarization and mild portal and lobular inflammation. Only the hepatitis C patient demonstrated fibrosis. One patient each had lobular neutrophilic microabscesses and macrovesicular steatosis. Proliferative ductular reactions were absent in CTE patients but present in all controls on PN for other reasons. MOC31 was absent in biliary epithelium and hepatocytes of all CTE patients; controls showed consistent strong membranous biliary epithelial and patchy membranous periportal hepatocyte staining. Our data show that, histologically, hepatopathy in CTE can be difficult to separate from comorbid disease including PN effect; however, the absent ductular reaction may be characteristic. MOC31 localization in the biliary epithelium and zone 1 hepatocytes of controls suggests these compartments of the liver might be most susceptible to effects of EpCAM deficiency. In addition, we validate the liver as suitable tissue for CTE diagnosis using MOC31 immunohistochemistry.
Detection and Classification of Bronchiectasis Through Convolutional Neural Networks
Authors: Aliboni Lorenzo , Pennati Francesca , Gelmini Alice , Colombo Alessandra , Ciuni Andrea , Milanese Gianluca , Sverzellati Nicola , Magnani Sandro , Vespro Valentina , Blasi Francesco , Aliverti Andrea , Aliberti Stefano
Published: March 2021

Purpose:

Bronchiectasis is a chronic disease characterized by an irreversible dilatation of bronchi leading to chronic infection, airway inflammation, and progressive lung damage. Three specific patterns of bronchiectasis are distinguished in clinical practice: cylindrical, varicose, and cystic. The predominance and the extension of the type of bronchiectasis provide important clinical information. However, characterization is often challenging and is subject to high interobserver variability. The aim of this study is to provide an automatic tool for the detection and classification of bronchiectasis through convolutional neural networks.

Materials and Methods:

Two distinct approaches were adopted: (i) direct network performing a multilabel classification of 32×32 regions of interest (ROIs) into 4 classes: healthy, cylindrical, cystic, and varicose and (ii) a 2-network serial approach, where the first network performed a binary classification between normal tissue and bronchiectasis and the second one classified the ROIs containing abnormal bronchi into one of the 3 bronchiectasis typologies. Performances of the networks were compared with other architectures presented in the literature.

Results:

Computed tomography from healthy individuals (n=9, age=47±6, FEV1%pred=109±17, FVC%pred=116±17) and bronchiectasis patients (n=21, age=59±15, FEV1%pred=74±25, FVC%pred=91±22) were collected. A total of 19,059 manually selected ROIs were used for training and testing. The serial approach provided the best results with an accuracy and F1 score average of 0.84, respectively. Slightly lower performances were observed for the direct network (accuracy=0.81 and F1 score average=0.82). On the test set, cylindrical bronchiectasis was the subtype classified with highest accuracy, while most of the misclassifications were related to the varicose pattern, mainly to the cylindrical class.

Conclusion:

The developed networks accurately detect and classify bronchiectasis disease, allowing to collect quantitative information regarding the radiologic severity and the topographical distribution of bronchiectasis subtype.
Vasopressor Responsiveness Beyond Arterial Pressure: A Conceptual Systematic Review Using Venous Return Physiology
Authors: Åneman Anders , Wilander Petter , Zoerner Frank , Lipcsey Miklos , Chew Michelle S.
Published: March 2021

We performed a systematic review to investigate the effects of vasopressor-induced hemodynamic changes in adults with shock. We applied a physiological approach using the interacting domains of intravascular volume, heart pump performance, and vascular resistance to structure the interpretation of responses to vasopressors. We hypothesized that incorporating changes in determinants of cardiac output and vascular resistance better reflect the vasopressor responsiveness beyond mean arterial pressure alone.

We identified 28 studies including 678 subjects in Pubmed, EMBASE, and CENTRAL databases.

All studies demonstrated significant increases in mean arterial pressure (MAP) and systemic vascular resistance during vasopressor infusion. The calculated mean systemic filling pressure analogue increased (16 ± 3.3 mmHg to 18 ± 3.4 mmHg; P = 0.02) by vasopressors with variable effects on central venous pressure and the pump efficiency of the heart leading to heterogenous changes in cardiac output. Changes in the pressure gradient for venous return and cardiac output, scaled by the change in MAP, were positively correlated (r
2 = 0.88, P < 0.001). Changes in the mean systemic filling pressure analogue and heart pump efficiency were negatively correlated (r
2 = 0.57, P < 0.001) while no correlation was found between changes in MAP and heart pump efficiency.

We conclude that hemodynamic changes induced by vasopressor therapy are inadequately represented by the change in MAP alone despite its common use as a clinical endpoint. The more comprehensive analysis applied in this review illustrates how vasopressor administration may be optimized.
Transmembrane protein DCBLD2 is correlated with poor prognosis and affects phenotype by regulating epithelial-mesenchymal transition in human glioblastoma cells
Authors: Cheng Shuai , Wang Liang-Yan , Wang Chuan-Hui , Wang Fa-Kai , Zhu Bing , Zhang Peng , Wang Guo-Hua
Published: March 2021

Objective

We attempt to investigate the biological function of the discoidin, complement C1r/C1s,Uegf, and Bmp1 and Limulus factor C, Coch, and Lgl domain-containing 2 (DCBLD2) in glioblastoma, as well as its effect on the epithelial-mesenchymal transition (EMT) process.

Methods

The public expression data of glioblastoma samples and normal brain samples from The Cancer Genome Atlas database, Genotype-Tissue Expression database and Chinese Glioma Genome Atlas database were used to analyze the expression of DCBLD2 and its relationship with the survival of patients with glioblastoma. Quantitative real-time PCR and western blot were used to evaluate mRNA and protein levels of DCBLD2. Cell viabilities were tested using Cell Counting Kit-8 and clone formation assays. Cell invasive and migratory abilities were measured by transwell assays.

Results

DCBLD2 expression was upregulated in glioblastoma and has a significantly positive correlation with the WHO classification. In addition, high expression of DCBLD2 was closely correlated with poor prognosis in primary and recurrent patients with glioblastoma. What is more, we found that knockdown of DCBLD2 notably reduced the cell proliferative, invasive and migratory capacities by elevating the expression of E-cadherin and inhibiting the expression of vimentin, snail, slug and twist. However, overexpression of DCBLD2 presented the opposite results.

Conclusion

The current study reveals that high expression of DCBLD2 is closely related to poor prognosis in glioblastoma and can significantly enhance the tumor cell viability and metastasis by activating the EMT process, suggesting that DCBLD2 may be a possible biomarker for glioblastoma treatment.
Decreased levels of γ-aminobutyric acid in temporal lobe of children with 47,XYY syndrome
Authors: Roberts Timothy P.L. , Bloy Luke , Miller Judith S. , Blaskey Lisa , Ross Judith
Published: March 2021

Background

47,XYY syndrome (XYY) is a male sex chromosome disorder where subjects have one X chromosome and two copies of the Y chromosome. XYY is associated with a physical phenotype and carries increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Imbalance of excitation and inhibition has been proposed as a putative biological basis of disorders such as ASD [1–3] and several studies have reported atypical brain γ-aminobutyric acid (GABA) levels in this population. Given the male preponderance in the prevalence of ASD, the unique presence of the Y chromosome in males leads to the intriguing possibility of investigating boys with XYY syndrome as a model of excess Y-chromosome genes.

Method

In this study, we investigated the associations of genotype and clinical phenotype with levels of GABA, estimated by regionally localized edited magnetic resonance spectroscopy in boys with 47, XYY syndrome compared to age-matched typically developing (XY) peers.

Results

Overall, we observed a decrease in GABA levels in XYY vs. XY, which appeared more significant in the left compared to the right hemisphere. There was no additional significant modulation of GABA levels in XYY according to presence/absence of ASD diagnosis. Interestingly, a positive correlation between bilateral GABA levels and testosterone levels was observed in pubescent XY boys that was not observed in XYY.

Conclusion

The inhibitory neurotransmitter GABA appears to be reduced in boys with 47,XYY, especially in the left hemisphere. Further, the typical association between GABA and testosterone levels, observed in older typically developing control boys was not evident in boys with 47,XYY.
Cool birds: facultative use by an introduced species of mechanical air conditioning systems during extremely hot outdoor conditions
Authors: Mills Raegan , McGraw Kevin J.
Published: March 2021

Rapid climate change across the globe is having dramatic effects on wildlife. Responses of organisms to shifting thermal conditions often include physiological and behavioural accommodations, but to date these have been largely viewed and studied as naturally evolved phenomena (e.g. heat avoidance, sweating, panting) and not necessarily as strategies where animals exploit other anthropogenic conditions or resources. Moreover, the degree to which native versus introduced species show thermal plasticity has generated much conservation and ecological interest. We previously have observed introduced rosy-faced lovebirds (Agapornis roseicollis) perching in the relief-air vents on building faces in the Phoenix, Arizona, USA, metropolitan area, but doing so only during summer. Here, we show that such vent-perching events are significantly associated with extreme outdoor summer temperatures (when daily local highs routinely exceed 40°C). In fact, the temperature threshold at which we detected lovebirds starting to perch in cool air vents mirrors the upper range of the thermoneutral zone for this species. These results implicate novel, facultative use of an anthropogenic resource—industrial air-conditioning systems—by a recently introduced species (within the last 35 years) to cool down and survive extremely hot conditions in this urban ‘heat-island' environment.
Aerosol formation due to a dental procedure: insights leading to the transmission of diseases to the environment
Authors: Mirbod Parisa , Haffner Eileen A. , Bagheri Maryam , Higham Jonathan E.
Published: March 2021

As a result of the outbreak and diffusion of SARS-CoV-2, there has been a directive to advance medical working conditions. In dentistry, airborne particles are produced through aerosolization facilitated by dental instruments. To develop methods for reducing the risks of infection in a confined environment, understanding the nature and dynamics of these droplets is imperative and timely. This study provides the first evidence of aerosol droplet formation from an ultrasonic scalar under simulated oral conditions. State-of-the-art optical flow tracking velocimetry and shadowgraphy measurements are employed to quantitatively measure the flow velocity, trajectories and size distribution of droplets produced during a dental scaling process. The droplet sizes are found to vary from 5 µm to 300 µm; these correspond to droplet nuclei that could carry viruses. The droplet velocities also vary between 1.3 m s
−1
and 2.6 m s
−1
. These observations confirm the critical role of aerosols in the transmission of disease during dental procedures, and provide invaluable knowledge for developing protocols and procedures to ensure the safety of both dentists and patients.
Computational investigations of the immune response to repeated influenza infections and vaccinations
Authors: Adabor Emmanuel S.
Published: March 2021

Previous studies have shown that repeated influenza vaccination can enhance susceptibility to subsequent infection with a drifted influenza virus strain. This paper seeks to further understanding of the interactions between influenza viruses and specific immune cells that accompany this phenomenon. The paper argues that repeated vaccination increases susceptibility to infection only in the context of a residual immunity induced by prior vaccination or infection. The results of computational analysis indicate that this is a dynamic consequence of interactions between vaccines, influenza viruses and specific immune cells. In particular, mathematical modelling was used to show that in the presence of residual immunity conferred by a vaccine administered in Canada in the 2013–2014 influenza season, the 2014–2015 season vaccine enhanced susceptibility to infection. Such infection enhancement occurs when the 2014–2015 vaccine boosts suppressive T-regulatory cells induced by the 2013–2014 vaccine, decreasing the strength of antibody responses to the infecting strain. Overall, the study suggests probable characteristics of infecting viruses and vaccines that make repeated influenza infections and vaccinations detrimental.
Angiogenic property of silk fibroin scaffolds with adipose-derived stem cells on chick chorioallantoic membrane
Authors: Watchararot Tanapong , Prasongchean Weerapong , Thongnuek Peerapat
Published: March 2021

Angiogenesis is a crucial step in tissue regeneration and repair. Biomaterials that allow or promote angiogenesis are thus beneficial. In this study, angiogenic properties of salt-leached silk fibroin (SF) scaffolds seeded with human adipose stem cells (hADSCs) were studied using chick chorioallantoic membrane (CAM) as a model. The hADSC-seeded SF scaffolds (SF-hADSC) with the porosity of 77.34 ± 6.96% and the pore diameter of 513.95 ± 4.99 µm were implanted on the CAM of chick embryos that were on an embryonic day 8 (E8) of development. The SF-hADSC scaffolds induced a spoke-wheel pattern of capillary network indicative of angiogenesis, which was evident since E11. Moreover, the ingrowth of blood vessels into the scaffolds was seen in histological sections. The unseeded scaffolds induced the same extent of angiogenesis later on E14. By contrast, the control group could not induce the same extent of angiogenesis.
In vitro
cytotoxicity tests and
in vivo
angioirritative study reaffirmed the biocompatibility of the scaffolds. This work highlighted that the biocompatible SF-hADSC scaffolds accelerate angiogenesis, and hence they can be a promising biomaterial for the regeneration of tissues that require angiogenesis.
How does external lateral stabilization constrain normal gait, apart from improving medio-lateral gait stability?
Authors: Mahaki Mohammadreza , IJmker Trienke , Houdijk Han , Bruijn Sjoerd Matthijs
Published: March 2021

Background: The effect of external lateral stabilization on medio-lateral gait stability has been investigated previously. However, existing lateral stabilization devices not only constrain lateral motions but also transverse and frontal pelvis rotations. This study aimed to investigate the effect of external lateral stabilization with and without constrained transverse pelvis rotation on mechanical and metabolic gait features. Methods: We undertook two experiments with 11 and 10 young adult subjects, respectively. Kinematic, kinetic and breath-by-breath oxygen consumption data were recorded during three walking conditions (normal walking (Normal), lateral stabilization with (Free) and without transverse pelvis rotation (Restricted)) and at three speeds (0.83, 1.25 and 1.66 m s
−1
) for each condition. In the second experiment, we reduced the weight of the frame, and allowed for longer habituation time to the stabilized conditions. Results: External lateral stabilization significantly reduced the amplitudes of the transverse and frontal pelvis rotations, in addition to medio-lateral, anterior–posterior, and vertical pelvis displacements, transverse thorax rotation, arm swing, step length and step width. The amplitudes of free vertical moment, anterior–posterior drift over a trial, and energy cost were not significantly influenced by external lateral stabilization. The removal of pelvic rotation restrictions by our experimental set-ups resulted in normal frontal pelvis rotation in Experiment 1 and significantly higher transverse pelvis rotation in Experiment 2, although transverse pelvis rotation still remained significantly less than in the Normal condition. Step length increased with the increased transverse pelvis rotation. Conclusion: Existing lateral stabilization set-ups not only constrain medio-lateral motions (i.e. medio-lateral pelvis displacement) but also constrain other movements such as transverse and frontal pelvis rotations, which leads to several other gait changes such as reduced transverse thorax rotation, and arm swing. Our new set-ups allowed for normal frontal pelvis rotation and more transverse pelvis rotation (yet less than normal). However, this did not result in more normal thorax rotation and arm swing. Hence, to provide medio-lateral support without constraining other gait variables, more elaborate set-ups are needed.
The skeleton ofCongruus kitcheneri, a semiarboreal kangaroo from the Pleistocene of southern Australia
Authors: Warburton Natalie M. , Prideaux Gavin J.
Published: March 2021

The macropodine kangaroo,Wallabia kitcheneri, was first described in 1989 from a Pleistocene deposit within Mammoth Cave, southwestern Australia, on the basis of a few partial dentaries and maxilla fragments. Here, we recognizeW. kitcheneriwithin the Pleistocene assemblages of the Thylacoleo Caves, south-central Australia, where it is represented by several cranial specimens and two near-complete skeletons, a probable male and female. We reallocate this species to the hitherto monotypic genusCongruus.Congruus kitcheneridiffers from all other macropodid species by having a highly unusual pocket within the wall of the nasal cavity. It is distinguished fromC. congruusby having a longer, narrower rostrum, a taller occiput and a deeper jugal.Congruusis closest toProtemnodonin overall cranial morphology but is smaller and less robust. In most postcranial attributes,Congruusalso resemblesProtemnodon, including general limb robustness and the atypical ratio of 14 thoracic to five lumbar vertebrae. It is distinguished by the high mobility of its glenohumeral joints, the development of muscle attachment sites for strong adduction and mobility of the forelimb, and large, robust manual and pedal digits with strongly recurved distal phalanges. These adaptations resemble those of tree-kangaroos more than ground-dwelling macropodines. We interpret this to imply thatC. kitcheneriwas semiarboreal, with a propensity to climb and move slowly through trees. This is the first evidence for the secondary adoption of a climbing habit within crown macropodines.
A theory of pattern formation for reaction–diffusion systems on temporal networks
Authors: Van Gorder Robert A.
Published: March 2021

Networks have become ubiquitous in the modern scientific literature, with recent work directed at understanding ‘temporal networks’—those networks having structure or topology which evolves over time. One area of active interest is pattern formation from reaction–diffusion systems, which themselves evolve over temporal networks. We derive analytical conditions for the onset of diffusive spatial and spatio-temporal pattern formation on undirected temporal networks through the Turing and Benjamin–Feir mechanisms, with the resulting pattern selection process depending strongly on the evolution of both global diffusion rates and the local structure of the underlying network. Both instability criteria are then extended to the case where the reaction–diffusion system is non-autonomous, which allows us to study pattern formation from time-varying base states. The theory we present is illustrated through a variety of numerical simulations which highlight the role of the time evolution of network topology, diffusion mechanisms and non-autonomous reaction kinetics on pattern formation or suppression. A fundamental finding is that Turing and Benjamin–Feir instabilities are generically transient rather than eternal, with dynamics on temporal networks able to transition between distinct patterns or spatio-temporal states. One may exploit this feature to generate new patterns, or even suppress undesirable patterns, over a given time interval.
Dimension reduction for thin films prestrained by shallow curvature
Authors: Jiménez Bolaños Silvia , Lewicka Marta
Published: March 2021

We are concerned with the dimension reduction analysis for thin three-dimensional elastic films, prestrained via Riemannian metrics with weak curvatures. For the prestrain inducing the incompatible version of the Föppl–von Kármán equations, we find the
Γ
-limits of the rescaled energies, identify the optimal energy scaling laws, and display the equivalent conditions for optimality in terms of both the prestrain components and the curvatures of the related Riemannian metrics. When the stretching-inducing prestrain carries no in-plane modes, we discover similarities with the previously described shallow shell models. In higher prestrain regimes, we prove new energy upper bounds by constructing deformations as the Kirchhoff–Love extensions of the highly perturbative, Hölder-regular solutions to the Monge–Ampere equation obtained by means of convex integration.
Thermal oscillations, second sound and thermal resonance in phonon hydrodynamics
Authors: Xu Mingtian
Published: March 2021

Recent observation of second sound in graphite at a temperature above 100 K has aroused a great interest in the study of thermal waves in non-metallic solid materials. In this article, based on the Guyer–Krumhansl model, we investigate the second sound and thermal resonance phenomena in phonon hydrodynamics. The occurrence condition for the second sound is derived. It shows that the smaller the relaxation time of N-scattering of the non-metallic solid with a large relaxation time of R-scattering, the more likely the second sound will occur. For the phonon transport in the non-metallic solid excited by an oscillatory heat source with a single frequency, the occurrence condition for thermal resonance and a formula for calculating the external heat source frequency at resonance are also derived. It is found that the low-dimensional materials with small size are prone to the occurrence of second sound and thermal resonance. These phenomena open up new avenues for thermal management and energy conversion.
Evidence for an Allee effect in a declining fur seal population
Authors: Nagel Rebecca , Stainfield Claire , Fox-Clarke Cameron , Toscani Camille , Forcada Jaume , Hoffman Joseph I.
Published: March 2021

Allee effects play an important role in the dynamics of many populations and can increase the risk of local extinction. However, some authors have questioned the weight of evidence for Allee effects in wild populations. We therefore exploited a natural experiment provided by two adjacent breeding colonies of contrasting density to investigate the potential for Allee effects in an Antarctic fur seal (
Arctocephalus gazella
) population that is declining in response to climate change-induced reductions in food availability. Biometric time-series data were collected from 25 pups per colony during two consecutive breeding seasons, the first of which was among the worst on record in terms of breeding female numbers, pup birth weights and foraging trip durations. In previous decades when population densities were higher, pup mortality was consistently negatively density dependent, with rates of trauma and starvation scaling positively with density. However, we found the opposite, with higher pup mortality at low density and the majority of deaths attributable to predation. In parallel, body condition was depressed at low density, particularly in the poor-quality season. Our findings shed light on Allee effects in wild populations and highlight a potential emerging role of predators in the ongoing decline of a pinniped species.
Whole-organism responses to constant temperatures do not predict responses to variable temperatures in the ecosystem engineer
Mytilus trossulus
Authors: Marshall Katie E. , Anderson Kathryn M. , Brown Norah E. M. , Dytnerski James K. , Flynn Kelsey L. , Bernhardt Joey R. , Konecny Cassandra A. , Gurney-Smith Helen , Harley Christopher D. G.
Published: March 2021

Understanding and predicting responses of ectothermic animals to temperature are essential for decision-making and management. The thermal performance curve (TPC), which quantifies the thermal sensitivity of traits such as metabolism, growth and feeding rates in laboratory conditions, is often used to predict responses of wild populations. However, central assumptions of this approach are that TPCs are relatively static between populations and that curves measured under stable temperature conditions can predict performance under variable conditions. We test these assumptions using two latitudinally matched populations of the ecosystem engineer
Mytilus trossulus
that differ in their experienced temperature variability regime. We acclimated each population in a range of constant or fluctuating temperatures for six weeks and measured a series of both short term (feeding rate, byssal thread production) and long-term (growth, survival) metrics to test the hypothesis that performance in fluctuating temperatures can be predicted from constant temperatures. We find that this was not true for any metric, and that there were important interactions with the population of origin. Our results emphasize that responses to fluctuating conditions are still poorly understood and suggest caution must be taken in the use of TPCs generated under constant temperature conditions for the prediction of wild population responses.