bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the image quality of elastic reverse-time migration in the dip-angle domain using deep learning
Authors: Lu Yongming , Sun Hui , Wang Xiaoyi , Liu Qiancheng , Zhang Hao
Published: June 2020

Elastic reverse-time migration (ERTM) is becoming increasingly feasible with the development of high-performance computing. It can provide more physical information on subsurface structures. However, the crosstalk artifacts degrade the imaging resolution of ERTM. To obtain high-resolution ERTM imaging, we have developed additional constraints through a convolutional neural network (CNN) in the dip-angle domain. This procedure can significantly improve the image quality of ERTM by recognizing the dominant reflection events and rejecting the crosstalk artifacts in the dip-angle domain. This method can be divided into the following three steps. First, we generate the dip-angle gathers of ERTM using Poynting vectors shot by shot. Then, we stack all the dip-angle gathers over all the shots. Finally, we adopt the CNN to predict the dip-angle constraint, which can suppress the crosstalk artifacts and enhance the ERTM image quality. The picking method using CNN is an end-to-end procedure that can perform automatic picking without additional human intervention once the network is well-trained. The numerical examples have verified the potential of our method.
Relationships Between Managerial and Organizational Practices, Psychological Health at Work, and Quality of Care in Pediatric Oncology
Authors: Lejeune Julien , Chevalier Severine , Fouquereau Evelyne , Chenevert Denis , Coillot Hélène , Binet Aurélien , Gillet Nicolas , Mokounkolo René , Michon Jean , Dupont Sophie , Rachieru Petronela , Gandemer Virginie , Colombat Philippe
Published: June 2020

PURPOSE:

Psychological health at work for care providers is an important issue, because they are directly involved in quality of patient care. Managerial and organizational determinants have been found to be indicators of psychological health at work. The main objective of this study was to explore the relationships between the psychological health at work of pediatric oncology care workers with managerial and organizational determinants and with quality of care.

MATERIALS AND METHODS:

We performed regression analysis between psychological health at work (quality of work life [QWL], job satisfaction, and so on), managerial determinants (transformational leadership, perceived autonomy support), organizational determinants (organizational support, organizational justice, and participatory approach), and perceived quality of care.

RESULTS:

Participants were 510 health care professionals working in French pediatric oncology centers. No significant differences in the psychological health at work of the participants were found based on age, sex, length of employment, or professional discipline. In simple regression, significant associations were found between psychological health at work with all managerial and organizational determinants. In multiple regression, a significant link was found between QWL and perceived organizational support (β = .21; P < .001), organizational justice (β = .20, P < .001), and overall participatory approach (β = .10; P < .02). Job satisfaction was also related to perceived organizational support (β = .16; P < .01). Finally, perceived quality of care was linked to QWL (β = .15; P < .01) and job satisfaction (β = .30; P < .001).

CONCLUSION:

These results emphasize the importance of the role of managers and the organization in psychological health at work of health care providers and also in the quality of patient care
Industry-Wide Survey of Academic Anesthesiology Departments Provides Up-to-Date Benchmarking Data on Surgical Anesthesia Productivity
Authors: Abouleish Amr E. , Hudson Mark E. , Levy Ronald S. , Whitten Charles W.
Published: June 2020

BACKGROUND:

Benchmarking group surgical anesthesia productivity continues to be an important but challenging goal for anesthesiology groups. Benchmarking is important because it provides objective data to evaluate staffing needs and costs, identify potential operating room management decisions that could reduce costs or improve efficiency, and support ongoing negotiations and discussions with health system leadership. Unfortunately, good and meaningful benchmarking data are not readily available. Therefore, a survey of academic anesthesiology departments was done to provide current benchmarking data.

METHODS:

A survey of members of the Society of Academic Associations of Anesthesiology and Perioperative Medicine (SAAAPM) was performed. The survey collected data by facility and included type of facility, number and type of staff and anesthetizing sites each weekday, and the billed American Society of Anesthesiologists (ASA) units and number of cases over 12 months. The facility types included academic medical center (AMC), community hospital (Community), children’s hospital (Children), and ambulatory surgical center (ASC). All anesthesia care billed using ASA units were included, except for obstetric anesthesia. Any care not billed or billed using relative value units (RVUs) were excluded. Percentage of nonoperating room anesthetizing sites, staffing ratio, and surgical anesthesia productivity measurements “per case” and “per site” were calculated.

RESULTS:

Of the 135 society members, 63 submitted complete surveys for 140 facilities (69 AMC, 26 Community, 7 Children, and 38 ASC). In the survey, overall median productivity for AMC and Children was similar (12,592 and 12,364 total ASA units per anesthetizing site), while the ASC had the lowest median overall productivity (8911 total ASA units per anesthetizing site). By size of facility, in the survey, the smaller facilities (<10 sites, ASC or non-ASC) had lower median overall productivity as compared to larger facilities. For AMC and Children, >20% of anesthetizing sites were nonoperating room anesthetizing sites. Anesthesiology residents worked primarily in AMC and Children. In ASC and Community, residents worked only in 18% and 35% of facilities, respectively. More than half the AMCs reported at least 1 break certified nurse anesthetist (CRNA) each day.

CONCLUSIONS:

To make data-driven decisions on clinical productivity, anesthesiology leaders need to be able to make meaningful comparisons at the facility level. For a group that provides care in multiple facilities, one can make internal comparisons among facilities and follow measurements over time. It is valuable for leaders to also be compare their facilities with industry-wide measurements, in other words, benchmark their facilities. These results provide benchmarking data for academic anesthesiology departments.
Propofol Attenuates Isoflurane-Induced Neurotoxicity and Cognitive Impairment in Fetal and Offspring Mice
Authors: Nie Yangyang , Li Shuai , Yan Tao , Ma Yiming , Ni Cheng , Wang Hongying , Zheng Hui
Published: June 2020

BACKGROUND:

Anesthesia in pregnant rodents causes neurotoxicity in fetal and offspring rodents. However, the underlying mechanisms and targeted treatments remain largely to be determined. Isoflurane and propofol are among commonly used anesthetics. Thus, we set out to investigate whether propofol can mitigate the isoflurane-induced neurotoxicity in mice.

METHODS:

Pregnant C57BL/6 mice at gestational day 15 (G15) were randomly assigned to 4 groups: control, isoflurane, propofol, and isoflurane plus propofol. Levels of interleukin (IL)-6 and poly-ADP ribose polymerase (PARP) fragment were measured in the brains of G15 embryos, and levels of postsynaptic density (PSD)-95 and synaptophysin were determined in the hippocampal tissues of postnatal day 31 (P31) offspring using Western blotting and immunohistochemical staining. Learning and memory functions in P31 offspring were determined using a Morris water maze test.

RESULTS:

Isoflurane anesthesia in pregnant mice at G15 significantly increased brain IL-6 (222.6% ± 36.45% vs 100.5% ± 3.43%, P < .0001) and PARP fragment (384.2% ± 50.87% vs 99.59% ± 3.25%, P < .0001) levels in fetal mice and reduced brain PSD-95 (30.76% ± 2.03% vs 100.8% ± 2.25%, P < .0001) and synaptophysin levels in cornu ammonis (CA) 1 region (57.08% ± 4.90% vs 100.6% ± 2.20%, P < .0001) and dentate gyrus (DG; 56.47% ± 3.76% vs 99.76% ± 1.09%, P < .0001) in P31 offspring. Isoflurane anesthesia also impaired cognitive function in offspring at P31. Propofol significantly mitigated isoflurane-induced increases in brain IL-6 (117.5% ± 10.37% vs 222.6% ± 36.45%, P < .0001) and PARP fragment (205.1% ± 35.99% vs 384.2% ± 50.87%, P < .0001) levels in fetal mice, as well as reductions in PSD-95 (49.79% ± 3.43% vs 30.76% ± 2.03%, P < .0001) and synaptophysin levels in CA1 region (85.57% ± 2.97% vs 57.08% ± 4.90%, P < .0001) and DG (85.05% ± 1.87% vs 56.47% ± 3.76%, P < .0001) in hippocampus of P31 offspring. Finally, propofol attenuated isoflurane-induced cognitive impairment in offspring.

CONCLUSIONS:

These findings suggest that gestational isoflurane exposure in mice induces neuroinflammation and apoptosis in embryos and causes cognitive impairment in offspring. Propofol can attenuate these isoflurane-induced detrimental effects.
A Novel Negative Pressure Isolation Device for Aerosol Transmissible COVID-19
Authors: Seger Christian D. , Wang Libing , Dong Xuezhi , Tebon Peyton , Kwon Sebastian , Liew Elaine C. , Marijic Jure , Umar Soban , Hoftman Nir N.
Published: June 2020

The coronavirus disease 2019 (COVID-19) pandemic creates a need to protect health care workers (HCWs) from patients undergoing aerosol-generating procedures which may transmit the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Existing personal containment devices (PCDs) may protect HCWs from respiratory droplets but not from potentially dangerous respiratory-generated aerosols. We describe a new PCD and its aerosol containment capabilities. The device ships flat and folds into a chamber. With its torso drape and protective arm sleeves mounted, it provides contact, droplet, and aerosol isolation during intubation and cardiopulmonary resuscitation (CPR). Significantly improved ergonomics, single-use workflow, and ease of removal distinguish this device from previously published designs.
The role of the diencephalon in the guidance of thalamocortical axons in mice
Authors: Quintana-Urzainqui Idoia , Hernández-Malmierca Pablo , Clegg James M. , Li Ziwen , Kozić Zrinko , Price David J.
Published: June 2020

Thalamocortical axons (TCAs) cross several tissues on their journey to the cortex. Mechanisms must be in place along the route to ensure they connect with their targets in an orderly fashion. The ventral telencephalon acts as an instructive tissue, but the importance of the diencephalon in TCA mapping is unknown. We report that disruption of diencephalic development by Pax6 deletion results in a thalamocortical projection containing mapping errors. We used conditional mutagenesis to test whether these errors are due to the disruption of pioneer projections from prethalamus to thalamus and found that, while this correlates with abnormal TCA fasciculation, it does not induce topographical errors. To test whether the thalamus contains navigational cues for TCAs, we used slice culture transplants and gene expression studies. We found the thalamic environment is instructive for TCA navigation and that the molecular cues Netrin1 and Semaphorin3a are likely to be involved. Our findings indicate that the correct topographic mapping of TCAs onto the cortex requires the order to be established from the earliest stages of their growth by molecular cues in the thalamus itself.
De novo enteric neurogenesis in post-embryonic zebrafish from Schwann cell precursors rather than resident cell types
Authors: El-Nachef Wael Noor , Bronner Marianne E.
Published: June 2020

The enteric nervous system (ENS) is essential for normal gastrointestinal function. While the embryonic origin of enteric neurons from the neural crest is well-established, conflicting evidence exists regarding postnatal enteric neurogenesis. Here, we address this by examining the origin of de novo neurogenesis in the post-embryonic zebrafish ENS. While new neurons are added during growth and after injury, the larval intestine appears to lack resident neurogenic precursors or classical glia marked by Sox10, PLP1a, GFAP or S100. Rather, lineage tracing with lipophilic dye or inducible Sox10-Cre suggest that post-embryonic enteric neurons arise from trunk neural crest-derived Schwann cell precursors that migrate from the spinal cord into the intestine. Furthermore, the 5-HT4 receptor agonist prucalopride increases enteric neurogenesis in normal development and after injury. Taken together, the results suggest that despite the lack of resident progenitors in the gut, post-embryonic enteric neurogenesis occurs via gut-extrinsic Schwann cell precursors during both development and injury, and is promoted by serotonin agonists. The absence of classical glia in the ENS further suggests that neural crest-derived enteric glia may have evolved after the teleost lineage.
mRNA localization is linked to translation regulation in theCaenorhabditis elegansgerm lineage
Authors: Parker Dylan M. , Winkenbach Lindsay P. , Boyson Sam , Saxton Matthew N. , Daidone Camryn , Al-Mazaydeh Zainab A. , Nishimura Marc T. , Mueller Florian , Nishimura Erin Osborne
Published: June 2020

Caenorhabditis elegans early embryos generate cell-specific transcriptomes despite lacking active transcription, thereby presenting an opportunity to study mechanisms of post-transcriptional regulatory control. We observed that some cell-specific mRNAs accumulate non-homogenously within cells, localizing to membranes, P granules (associated with progenitor germ cells in the P lineage), and P-bodies (associated with RNA processing). The subcellular distribution of transcripts differed in their dependence on 3′UTRs and RNA Binding Proteins, suggesting diverse regulatory mechanisms. Notably, we found strong but imperfect correlations between low translational status and P granule localization within the progenitor germ lineage. By uncoupling translation from mRNA localization, we untangled a long-standing question: Are mRNAs directed to P granules to be translationally repressed, or do they accumulate there as a consequence of this repression? We found that translational repression preceded P granule localization and could occur independently of it. Further, disruption of translation was sufficient to send homogenously distributed mRNAs to P granules. These results implicate transcriptional repression as a means to deliver essential maternal transcripts to the progenitor germ lineage for later translation.
A SMAD1/5-YAP signaling module drives radial glia self-amplification and growth of the developing cerebral cortex
Authors: Najas Sonia , Pijuan Isabel , Esteve-Codina Anna , Usieto Susana , Martinez Juan D. , Zwijsen An , Arbonés Maria L. , Martí Elisa , Le Dréau Gwenvael
Published: June 2020

The growth and evolutionary expansion of the cerebral cortex are defined by the spatial-temporal production of neurons, which itself depends on the decision of radial glial cells (RGCs) to self-amplify or to switch to neurogenic divisions. The mechanisms regulating these RGC fate decisions are still incompletely understood. Here we describe a novel and evolutionarily conserved role of the canonical BMP transcription factors SMAD1/5 in controlling neurogenesis and growth during corticogenesis. Reducing the expression of both SMAD1 and SMAD5 in neural progenitors at early mouse cortical development caused microcephaly and an increased production of early-born cortical neurons at the expense of late-born ones, which correlated with the premature differentiation and depletion of the pool of cortical progenitors. Gain- and loss-of-function experiments performed during early cortical neurogenesis in the chick revealed that SMAD1/5 activity supports self-amplifying RGC divisions and restrain the neurogenic ones. Furthermore, we demonstrate that SMAD1/5 stimulate RGC self-amplification through the positive post-transcriptional regulation of the Hippo signaling effector YAP. We anticipate this SMAD1/5-YAP signaling module to be fundamental in controlling growth and evolution of the amniote cerebral cortex.
The KMT2D Kabuki syndrome histone methylase controls neural crest cell differentiation and facial morphology
Authors: Shpargel Karl B. , Mangini Cassidy L. , Xie Guojia , Ge Kai , Magnuson Terry
Published: June 2020

Kabuki syndrome (KS) is a congenital craniofacial disorder resulting from mutations in the KMT2D histone methylase (KS1) or the UTX histone demethylase (KS2). With small cohorts of KS2 patients, it is not clear if differences exist in clinical manifestations relative to KS1. We mutated KMT2D in neural crest cells (NCCs) to study cellular and molecular functions in craniofacial development with respect to UTX. Similar to UTX, KMT2D NCC knockout mice demonstrate hypoplasia with reductions in frontonasal bone lengths. We have traced the onset of KMT2D and UTX mutant NCC frontal dysfunction to a stage of altered osteochondral progenitor differentiation. KMT2D NCC loss of function does exhibit unique phenotypes distinct from UTX mutation including fully penetrant cleft palate, mandible hypoplasia, and deficits in cranial base ossification. KMT2D mutant NCCs lead to defective secondary palatal shelf elevation with reduced expression of extracellular matrix components. KMT2D mutant chondrocytes in the cranial base fail to properly differentiate leading to defective endochondral ossification. We conclude that KMT2D is required for appropriate cranial NCC differentiation and KMT2D specific phenotypes may underlie differences between Kabuki syndrome subtypes.
Reclaiming Warburg: using developmental biology to gain insight into human metabolic diseases
Authors: Drummond-Barbosa Daniela , Tennessen Jason M.
Published: June 2020

Developmental biologists have frequently pushed the frontiers of modern biomedical research. From the discovery and characterization of novel signal transduction pathways to exploring the molecular underpinnings of genetic inheritance, transcription, the cell cycle, cell death and stem cell biology, studies of metazoan development have historically opened new fields of study and consistently revealed previously unforeseen avenues of clinical therapies. From this perspective, it is not surprising that our community is now an integral part of the current renaissance in metabolic research. Amidst the global rise in metabolic syndrome, the discovery of novel signaling roles for metabolites, and the increasing links between altered metabolism and many human diseases, we as developmental biologists can contribute skills and expertise that are uniquely suited for investigating the mechanisms underpinning human metabolic health and disease. Here, we summarize the opportunities and challenges that our community faces, and discuss how developmental biologists can make unique and valuable contributions to the field of metabolism and physiology.
Stromal beta-catenin activation impacts nephron progenitor differentiation in the developing kidney and may contribute to Wilms tumor
Authors: Drake Keri A. , Chaney Christopher P. , Das Amrita , Roy Priti , Kwartler Callie S. , Rakheja Dinesh , Carroll Thomas J.
Published: June 2020

Wilms tumor (WT) morphologically resembles the embryonic kidney, consisting of blastema, epithelial, and stromal components, suggesting tumors arise from the dysregulation of normal development. Beta-catenin activation is observed in a significant proportion of WTs; however, much remains to be understood about how it contributes to tumorigenesis. While activating beta-catenin mutations are observed in both blastema and stromal components of WT, current models assume that activation in the blastemal lineage is causal. Paradoxically, studies performed in mice suggest that activation of beta-catenin in the nephrogenic lineage results in loss of nephron progenitor cell (NPC) renewal, a phenotype opposite to WT. Here, we show that activation of beta-catenin in the stromal lineage non-autonomously prevents the differentiation of NPCs. Comparisons of the transcriptomes of kidneys expressing an activated allele of beta-catenin in the stromal or nephron progenitor cells reveals that human WT more closely resembles the stromal-lineage mutants. These findings suggest that stromal beta-catenin activation results in histological and molecular features of human WT, providing insights into how alterations in the stromal microenvironment may play an active role in tumorigenesis.
The RALF1-FERONIA interaction modulates endocytosis to mediate control of root growth in Arabidopsis
Authors: Yu Meng , Li Ruili , Cui Yaning , Chen Weijun , Li Bin , Zhang Xi , Bu Yufen , Cao Yangyang , Xing Jingjing , Jewaria Pawan Kumar , Li Xiaojuan , Bhalerao Rishikesh , Yu Feng , Lin Jinxing
Published: June 2020

The interaction between the receptor-like kinase (RLK) FERONIA (FER) and the secreted peptide Rapid Alkalinization Factor 1 (RALF1) is vital for development and stress responses in Arabidopsis. Ligand-induced membrane dynamics affect the function of several RLKs, but the effects of the RALF1-FER interaction on the dynamics of FER and the ensuing effects on its functionality are poorly understood. Here, we show that RALF1 modulated the dynamics and partitioning of FER-GFP at the plasma membrane (PM). Moreover, FER was internalized by both clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE) under steady state conditions. After RALF1 treatment, FER-GFP internalization was primarily enhanced via the CME pathway, raising FER-GFP levels in the vacuole. RALF1 treatment also modulated trafficking of other PM proteins such as PIN2-GFP and BRI1-GFP, increasing their vacuolar levels by enhancing their internalization. Importantly, blocking CME attenuated RALF1-mediated root growth inhibition independently of RALF1-induced early signaling, suggesting that the RALF1 can also exert its effects via the CME pathway. These findings reveal that the RALF1-FER interaction modulates plant growth and development and this may also involve endocytosis of PM proteins.
Simultaneous deletion of Prdm1 and Vsx2 enhancers in the retina alters photoreceptor and bipolar cell fate specification, yet differs from deleting both genes
Authors: Goodson Noah B. , Kaufman Michael A. , Park Ko U. , Brzezinski Joseph A.
Published: June 2020

The transcription factor Otx2 is required for photoreceptor and bipolar cell formation in the retina. It directly activates the transcription factors Prdm1 and Vsx2 through cell type-specific enhancers. Prdm1 and Vsx2 work in opposition, such that Prdm1 promotes photoreceptor fate and Vsx2 bipolar cell fate. To determine how OTX2+ cell fates are regulated, we deleted Prdm1 and Vsx2 or their cell type-specific enhancers simultaneously using a CRISPR/Cas9 in vivo retina electroporation strategy. Double gene or enhancer targeting effectively removed PRDM1 and VSX2 protein expression. However, double enhancer targeting favored bipolar fate outcomes whereas double gene targeting favored photoreceptor fates. Both conditions generated excess amacrine cells. Combined, these fate changes suggest that photoreceptors are a default fate outcome in OTX2+ cells and that VSX2 must be present in a narrow temporal window to drive bipolar cell formation. Prdm1 and Vsx2 also appear to redundantly restrict the competence of OTX2+ cells, preventing amacrine cell formation. By taking a combinatorial deletion approach of both coding sequences and enhancers, our work provides new insights into the complex regulatory mechanisms that control cell fate choice.
Connexin43 gap junctional intercellular communication inhibits evx1 expression and joint formation in regenerating fins
Authors: Bhattacharya Shashwati , Hyland Caitlin , Falk Matthias M. , Iovine M. Kathryn
Published: June 2020

The gap junction protein Connexin43 (Cx43) contributes to cell fate decisions that determine the location of fin ray joints during regeneration. Here, we provide insights into how Cx43, expressed medially, influences changes in gene expression in lateral skeletal precursor cells. Using the Gap27 peptide inhibitor specific to Cx43, we show that Cx43-gap junctional intercellular communication (GJIC) influences Cx43-dependent skeletal phenotypes, including segment length. We also demonstrate that Cx43-GJIC influences expression of the Smp/β-catenin pathway in the lateral skeletal precursor cells, and does not influence the Sema3d pathway. Moreover, we show that the cx43 lh10 allele, which has increased Cx43 protein levels, exhibits increased regenerate length and segment length. These phenotypes are rescued by Gap27, suggesting that increased Cx43 is responsible for the observed Cx43 phenotypes. Finally, our findings suggest that inhibition of Cx43 hemichannel activity does not influence Cx43-dependent skeletal phenotypes. These data provide evidence that Cx43-GJIC is responsible for regulating cell fate decisions associated with appropriate joint formation in the regenerating fin.
An interview with Samantha Morris
Authors: Grewal Seema
Published: June 2020

Samantha Morris is an Assistant Professor of Genetics and Developmental Biology at Washington University in St Louis, and an Allen Distinguished Investigator. Her lab aims to understand how cell identity can be reprogrammed, focusing on the gene regulatory networks that define cell identity and applying this knowledge to engineer clinically important cell types. Sam has also been a pioneer in developing novel single-cell technologies and, earlier this year, she joined Development as an Associate Editor, where she'll be providing expertise on single-cell approaches in developmental and stem cell biology. We caught up with Sam to ask her more about her career and her role at Development.
Cytoskeletal organization through multivalent interactions
Authors: Braun Marcus , Diez Stefan , Lansky Zdenek
Published: June 2020

The cytoskeleton consists of polymeric protein filaments with periodic lattices displaying identical binding sites, which establish a multivalent platform for the binding of a plethora of filament-associated ligand proteins. Multivalent ligand proteins can tether themselves to the filaments through one of their binding sites, resulting in an enhanced reaction kinetics for the remaining binding sites. In this Opinion, we discuss a number of cytoskeletal phenomena underpinned by such multivalent interactions, namely (1) generation of entropic forces by filament crosslinkers, (2) processivity of molecular motors, (3) spatial sorting of proteins, and (4) concentration-dependent unbinding of filament-associated proteins. These examples highlight that cytoskeletal filaments constitute the basis for the formation of microenvironments, which cytoskeletal ligand proteins can associate with and, once engaged, can act within at altered reaction kinetics. We thus argue that multivalency is one of the properties crucial for the functionality of the cytoskeleton.
αvβ8 integrin adhesion and signaling pathways in development, physiology and disease
Authors: McCarty Joseph H.
Published: June 2020

Cells must interpret a complex milieu of extracellular cues to modulate intracellular signaling events linked to proliferation, differentiation, migration and other cellular processes. Integrins are heterodimeric transmembrane proteins that link the extracellular matrix (ECM) to the cytoskeleton and control intracellular signaling events. A great deal is known about the structural and functional properties for most integrins; however, the adhesion and signaling pathways controlled by αvβ8 integrin, which was discovered nearly 30 years ago, have only recently been characterized. αvβ8 integrin is a receptor for ECM-bound forms of latent transforming growth factor β (TGFβ) proteins and promotes the activation of TGFβ signaling pathways. Studies of the brain, lung and immune system reveal that the αvβ8 integrin–TGFβ axis mediates cell–cell contact and communication within complex multicellular structures. Perturbing components of this axis results in aberrant cell–cell adhesion and signaling leading to the initiation of various pathologies, including neurodegeneration, fibrosis and cancer. As discussed in this Review, understanding the functions for αvβ8 integrin, its ECM ligands and intracellular effector proteins is not only an important topic in cell biology, but may lead to new therapeutic strategies to treat human pathologies related to integrin dysfunction.
Quantitative and Spatial Analysis of CD8+/PD-1 Tumor-Infiltrating Lymphocytes as a Predictive Biomarker for Clinical Response of Melanoma In-Transit Metastases to Topical Immunotherapy
Authors: Haywood Sophia , Garioch Jennifer , Ramaiya Arjun , Moncrieff Marc
Published: June 2020

Background

Melanoma in-transit metastases (ITMs) are a challenge to treat and associated with systemic disease and poor prognosis. Topical diphencyprone (DPCP), a potent contact sensitizer, is an established treatment for melanoma ITMs. This exploratory study investigated the utility of BRAF mutation status, CD8, PD-1, PD-L1, and TILs distribution as biomarkers for response of ITMs to topical immunotherapy (DPCP).

Methods

The ITM deposits of 40 patients treated with DPCP were subjected to biomarker analysis for BRAF status, CD8 and PD-1 expression on tumor-infiltrating lymphocytes (TILs), and tumor PD-L1 expression. Response to DPCP and overall survival (OS) were compared by biomarker status.

Results

After 12 weeks, 10 patients (25%) had a complete response, 12 patients (30%) had a partial response, and 18 patients (45%) had no response. No significant association was found between any individual biomarker and response to DPCP or OS. The BRAF mutation rate was 25% (10/40). All the patients with a complete response had BRAF wild-type tumor. Peritumoral CD8+ T-cells were associated with complete response (P = 0.041). Both CD8+ and PD-1 expressions were highly correlated (P < 0.0001), and the highest levels of PD-1 expression were detected at the peritumoral interface (P = 0.0004). Only two cases were PD-L1-positive, and both had a complete response to DPCP (P = 0.043).

Conclusion

Patients who have BRAF wild-type tumor are more likely to experience a complete response to DPCP. Peritumoral TILs and PD-1 expressions may predict a better response to DPCP. Expression of PD-L1 may be associated with a complete response to DPCP. A larger prospective study is required.
Frequency of depression, anxiety and stress among university students
Authors: Asif Saba , Muddassar Azka , Shahzad Talala Zainab , Raouf Mobeen , Pervaiz Tehmina
Published: June 2020

Objective: The main objective of the present study was to explore the frequency of Depression, anxiety and stress among university students in Sialkot, Pakistan.

Method: Survey research method was used to collect data from three universities of Sialkot by using simple random sampling technique from 500 university students. The study was conducted at GC Women University, Sialkot in total duration of five months from February 2019 to June 2019. A demographic sheet and DASS-21 (Depression, Anxiety Stress Scale) were used to measure the level of depression, anxiety and stress. Data was scored according to the standard scoring procedure for each subscale and for further analysis frequency distribution method was applied through statistical package for social sciences (SPSS. 21).

Results: The means of Depression, Anxiety and stress are M=15.08, M=18.24 and M=19.02 respectively. The frequency of depression, anxiety and stress among university students was found 75%, 88.4% and 84.4% respectively. The findings of the study showed the prevalence of Depression within the range of normal (25%), mild (16%), moderate (35.8%), severe (14.6%) and extremely severe (8.6%). The prevalence of anxiety was found to be in the range of normal (11.6%), mild (4.4%), moderate (19.4%), severe (17.8%) and extremely severe (46.8%). Stress was normal (15.6%), mild (33.8%), moderate (35.4%), severe (13.2%) and extremely severe (2.8%).

Conclusion: It is concluded that symptoms of anxiety and stress are more prevalent with moderate to extremely severe range than depression in the current sample. These findings suggest urgent need of some preventive measures and interventions to improve the mental health of students.

doi: https://doi.org/10.12669/pjms.36.5.1873

How to cite this:Asif S, Mudassar A, Shahzad TZ, Raouf M, Pervaiz T. Frequency of depression, anxiety and stress among university students. Pak J Med Sci. 2020;36(5):971-976. doi: https://doi.org/10.12669/pjms.36.5.1873

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Science in the School Playground
Authors: Cavalheiro A. , Calvo E. , Santos M. A. , Costa V.
Published: June 2020

How to improve our school playground? Based on the school plan and the surrounding area, it was decided to promote scientific activities in the playground by sharing scientific knowledge. In these activities, 20 pupils and 4 teachers participated as organizers, covering a community of 244 pupils (ages 3-10), 18 teachers and 11 other school staff. We chose a set of scientific questions, connected with the knowledge of space, the influence of the Sun in our lives, and with the protection of bats. We promote the questions through two tools: a conference and an exhibition, both organized by the students. The conferences were prepared in small groups, by exploring and using reliable scientific sources such as Ciência Viva science centres and ESERO Portugal. In the exhibition, scientific knowledge was offered at the school playground, in an experimental, interactive and dynamic approach, where we were the facilitators and guides of the other students and the educational community.
The Invasion of Microplastics
Authors: Machado C.
Published: June 2020

The project consisted of a market study, in order to know the attitudes of the inhabitants of Vila Nova de Famalicão (VNF) towards the use of plastic and to measure the knowledge of the population of VNF about microplastics. Students of various grades that were interested in the theme carried out the project. The main goal was to change mentalities and consequent practices. It was  concluded that, although the inhabitants of VNF know what microplastics areand what is at their origin, they do not reveal much concern in changing their daily practices because practical solutions are still not implemented.
Protect Bees, Save the Future
Authors: Madaleno I. , Branco S.
Published: June 2020

In this project, students built a hive by adapting remote control systems for its internal environment (temperature and humidity) and external environment (door, fire, location). The solution was aimed at beekeepers, and anyone interested in getting started in the beekeeping industry. The main goals of the project were to facilitate the work of beekeepers and to improve the management, control, and monitoring of hives. The solution created is feasible and satisfies the project's objectives.
Let's Change the Playground Floor!
Authors: Duarte L. , Ferreira R.
Published: June 2020

This project aims at the requalification of the floor of the school’s playground. Students organized class assemblies and students’ representative assemblies, and during these meetings they identified as a problem the floor full of irregular pebbles in the playground, very popular equipment in school. The pebbles have caused some accidents and, when it rains, they take a long time to dry, preventing the use of the park. During the assemblies, students tried to findways to solve the problem: they collected information, talked to parents and contacted different entities. The project is still ongoing but has already allowed students to learn much from it.
The School for us and us for the School
Authors: Xisto S. , Catarino D.
Published: June 2020

The main purpose of this project was to make the school more appealing, by working in the greenhouse, green spaces and leisure places. Transforming the school and making it a more active and welcoming place, was, from the beginning, the problem that was identified by the students. In their opinion, the school looked a little sad and they knew they would need help to transform it into a better place, where they could feel like home. With this purpose in mind, students attended a meeting with the local authorities and the Parents’ Association. To start the project, students made healthy gums to offer to other students, on Valentine’s Day, andthey also made soaps to sell to the community. These activities allowed us to begin the greenhouse project. The occupation of these young people’s free time became different and it was a very enriching experience. The seed of the OSOS project is germinating, and we believe that, in the future, it will continue to give beautiful flowers. Together we were able to make thedifference!
Green School
Authors: Serra S. , Afonso P. , Duarte T.
Published: June 2020

The interdisciplinary project, including the school disciplines of Natural Sciences, Mathematics, Expressions, Portuguese, ICT, History, and geography of Portugal. The project emerged from the students' interests and needs when observing the school space. An action plan for the improvement of green spaces was created through the creation of a school garden. The students were involved in planning, creating partnerships, executing and maintaining theproject. During the school year, there was a change in behaviour in relation to the garden and the care for the school green spaces by the students involved, but also by the school community.
Growing with Values
Authors: Santos S. , Fonseca C.
Published: June 2020

This project aims to alert, raise awareness, research and learn from an environmental protection perspective. The project intends to explore the ecosystems and biodiversity, from the school curriculum of different subject areas (Natural Sciences, Mathematics, Portuguese, Citizenship and Artistic Expressions). This is made through the principles of the scientific method, observation, data collection, experimentation, fieldwork, exchange andcommunication of ideas, as well as cooperation and partnership with  different entities. With this project, it is intended to make children observe the surrounding environment, collect information outside the classroom, categorize what they observed and find solutions to real environmental problems. In this way, it is possible to bring students closer to biodiversityissues, such as “Pollination in urban environments”, “Why are there few insects in urban environments?” and "What is the importance of insects for pollination and the balance of ecosystems?"
Learning to make informed health choices: Protocol for a pilot study in schools in Barcelona
Authors: Martínez García Laura , Alonso-Coello Pablo , Asso Ministral Laia , Ballesté-Delpierre Clara , Canelo Aybar Carlos , de Britos Carol , Fernández Rodríguez Ana , Gallego Iborra Ana , Leo Rosas Victoria , Llaquet Paloma , Niño de Guzmán Quispe Ena Pery , Pérez-Gaxiola Giordano , Requeijo Carolina , Salas-Gama Karla , Samsó Jofra Laura , Terres Jordi , Urreta Iratxe , Rosenbaum Sarah
Published: June 2020

Introduction: The Informed Health Choices (IHC) project has developed learning resources to teach primary school children (10 to 12-year-olds) to assess treatment claims and make informed health choices. The aim of our study is to explore both the students’ and teachers’ experience when using these resources in the context of Barcelona (Spain).

Methods: During the 2019-2020 school year, we will conduct a pilot study with 4 th and 5 th-year primary school students (9 to 11-year-olds) from three schools in Barcelona. The intervention in the schools will include: 1) a workshop with the teachers, and 2) lessons to the students. The data collection will include: 1) assessment of the IHC resources by the teachers before the lessons, 2) non-participatory observations during the lessons, 3) semi-structured interviews with the students after a lesson, 4) assessment of the lessons by the teachers after a lesson, 5) treatment claim assessment by the students at the end of the lessons, and 6) assessment of the IHC resources by the teachers at the end of the lessons. We will use ad hoc questionnaires and guides to register the data. We will perform a quantitative and qualitative analysis of the data to explore understandability, desirability, suitability, usefulness, facilitators and barriers of the resources. The most relevant results will be discussed and some recommendations on how to use, how to adapt (if needed), and how to implement the IHC resources to this context will be agreed. The findings of the contextualization activities could inform the design of a cluster-randomised trial, to determine the effectiveness of the IHC resources in this context prior to scaling-up its use.

Ethical considerations: The study protocol has obtained an approval exemption from the Ethics Committee of the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain).
Case Report: Dilated cardiomyopathy with biventricular thrombus secondary to impaired coagulation in a patient with HIV
Authors: Kammari Chetan Brahma , Rallabandi Suhasini , Rallabandi Harsha , Daggubati Subba Rao , Adapa Sreedhar , Naramala Srikanth , Konala Venu Madhav
Published: June 2020

Human immunodeficiency virus (HIV) infection is a known hypercoagulable state with venous thromboembolism with a high mortality rate compared to the general population. The homeostatic balance in HIV infected patients improves with treatment compared to those who are not.  A decreased hypercoagulable state noted by low levels of Von Willebrand factor, factor VIII and d-dimer levels along with higher protein C and S activity in patients on treatment suggests that hypercoagulable state is partially correctable with highly active antiretroviral therapy.  HIV with heart muscle involvement can present as myocarditis or as dilated cardiomyopathy with left or right ventricular dysfunction.  Here we present a case of a 57-year-old man with a known history of HIV infection, noncompliant with medical therapy presenting with dilated cardiomyopathy with biventricular thrombi with reduced protein C, protein S, and Antithrombin III levels.
Further investigation of gateway effects using the PATH study
Authors: Lee Peter N , Fry John S
Published: June 2020

Background: Interest exists in whether youth e-cigarette use (“vaping”) increases risk of initiating cigarette smoking. Using Waves 1 and 2 of the US PATH study we reported that adjustment for vaping propensity using Wave 1 variables explained about 80% of the unadjusted relationship. Here we use data from Waves 1 to 3 to avoid over-adjustment if Wave 1 vaping affected variables recorded then.

Methods: Our main analysis M1 concerned Wave 2 never smokers who never vaped by Wave 1, linking Wave 2 vaping to Wave 3 smoking initiation, adjusting for Wave 1 predictors. We conducted sensitivity analyses that: excluded Wave 1 other tobacco product users; included other product use as an extra predictor; or considered propensity for smoking or any tobacco use, rather than vaping. We also conducted analyses that: adjusted for propensity as derived originally; ignored Wave 1 data; used exact age (not previously available) as a confounder rather than grouped age; attempted residual confounding adjustment by modifying predictor values using data recorded later; or considered interactions with age.

Results: In M1, adjustment removed about half the excess OR (i.e. OR–1), the unadjusted OR, 5.60 (95% CI 4.52-6.93), becoming 3.37 (2.65-4.28), 3.11 (2.47-3.92) or 3.27 (2.57-4.16), depending whether adjustment was for propensity as a continuous variable, as quintiles, or for the variables making up the propensity score. Many factors had little effect: using grouped or exact age; considering other products; including interactions; or using predictors of smoking or tobacco use rather than vaping. The clearest conclusion was that analyses avoiding over-adjustment explained about half the excess OR, whereas analyses subject to over-adjustment explained about 80%.

Conclusions: Although much of the unadjusted gateway effect results from confounding, we provide stronger evidence than previously of some causal effect of vaping, though some doubts still remain about the completeness of adjustment.
Case Report: Simultaneously diagnosed gastric adenocarcinoma and pernicious anemia – a classic association
Authors: Kamran Syed , Dilling Mattias K. , Parker Nathaniel A. , Alderson Joel , Tofteland Nathan D. , Truong Quoc V.
Published: June 2020

Primary gastric cancer remains one of the most prevalent malignancies worldwide. Often patients remain asymptomatic until it is detected at an advanced stage with a poor prognosis. Thus, it’s characteristically difficult to initially diagnose until it becomes late stage, at which point prognosis becomes poor. Pernicious anemia is a classic risk factor for the development of primary gastric cancer, but is uncommonly seen in clinical practice. Over time, patients who produce the autoantibodies to intrinsic factor that cause pernicious anemia typically will present initially with clinically significant megaloblastic anemia and peripheral neuropathy. However, patients can also present with more nonspecific signs and symptoms. Thus, clinicians should remain vigilant as circulating anti-intrinsic factor antibodies only worsen the disease over time and increase the risk of developing primary gastric cancer. This report not only presents the rare concurrent diagnosis of pernicious anemia and gastric cancer, but also aims to increase clinical awareness of these two conditions’ classic association because early diagnosis and treatment significantly impacts morbidity and mortality.
Optimization for L1-Norm Error Fitting via Data Aggregation
Authors: Park Young Woong
Published: June 2020

We propose a data aggregation-based algorithm with monotonic convergence to a global optimum for a generalized version of the L1-norm error fitting model with an assumption of the fitting function. The proposed algorithm generalizes the recent algorithm in the literature, aggregate and iterative disaggregate (AID), which selectively solves three specific L1-norm error fitting problems. With the proposed algorithm, any L1-norm error fitting model can be solved optimally if it follows the form of the L1-norm error fitting problem and if the fitting function satisfies the assumption. The proposed algorithm can also solve multidimensional fitting problems with arbitrary constraints on the fitting coefficients matrix. The generalized problem includes popular models, such as regression and the orthogonal Procrustes problem. The results of the computational experiment show that the proposed algorithms are faster than the state-of-the-art benchmarks for L1-norm regression subset selection and L1-norm regression over a sphere. Furthermore, the relative performance of the proposed algorithm improves as data size increases.
Is Less More? A conservative multidisciplinary approach to ameloblastoma
Authors: Mohamedbhai Hussein , Dasgupta Debipriya , Hubbett Charlotte , Ali Nayeem
Published: June 2020

This case report outlines a novel conservative surgical approach to the management of a unicystic ameloblastoma with the use of marsupialisation, enucleation, cryotherapy and orthodontic extrusion to enable successful treatment without neurological damage or deformity. It has been increasingly recognized that conservative treatment of unicystic ameloblastomas, instead of wide local excision, can reduce morbidity whilst maintaining an acceptably low recurrence rate. Several case series have also demonstrated orthodontic extrusion of impacted third molars in moving the apex of the roots away from the inferior alveolar nerve. This is possibly the first case report of the combination of these two procedures in an adult with a large unicystic ameloblastoma.

CPD/Clinical Relevance: This is not an infrequently seen neoplasia: this paper therefore has the opportunity to inform management of this condition amongst clinicians.