Publications by authors named "L T T Le"

1,043 Publications

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The cost of Medicare-funded medical and pharmaceutical services for mental disorders in children and adolescents in Australia.

PLoS One 2021 9;16(4):e0249902. Epub 2021 Apr 9.

School of Health and Social Development, Deakin University, Geelong, Australia.

Objective: To examine the health care costs associated with mental disorders and subthreshold mental disorders within a nationally representative sample of children and adolescents in Australia.

Method: Data were derived from the Young Minds Matter Survey (N = 6,310). Mental disorders were classified using the Diagnostic Interview Schedule for Children Version IV. Participant data were linked to administrative data on health care costs. Adjusted generalized linear regression models and two-part models were used to estimate mean differences in costs between those with a mental disorder or subthreshold disorder and those without.

Results: Costs associated with health care attendances and medications were higher for children and adolescents with mental disorders and subthreshold mental disorders compared to those without a mental disorder. The additional population health care costs due to mental disorders amounted to AUD$234 million annually in children and adolescents, of which approximately 16% was attributed to out-of-pocket costs. Findings showed that those with subthreshold mental disorders or comorbid mental disorders have substantial additional costs of Medicare-funded medical and pharmaceutical services.

Conclusion And Implication: Mental disorders in children and adolescents are associated with significant health care costs. Further research is needed to ensure that this population is receiving effective and efficient care.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249902PLOS
April 2021

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Authors:
Jean Bousquet Ioana Agache Hubert Blain Marek Jutel Maria Teresa Ventura Margitta Worm Stefano Del Giacco Athanasios Benetos M Beatrice Bilo Wienczyslawa Czarlewski Amir Hamzah Abdul Latiff Mona Al-Ahmad Elizabeth Angier Isabella Annesi-Maesano Marina Atanaskovic-Markovic Claus Bachert Annick Barbaud Anna Bedbrook Kazi S Bennoor Elena Camelia Berghea Carsten Bindslev-Jensen Sergio Bonini Sinthia Bosnic-Anticevich Knut Brockow Luisa Brussino Paulo Camargos G Walter Canonica Victoria Cardona Pedro Carreiro-Martins Ana Carriazo Thomas Casale Jean-Christoph Caubet Lorenzo Cecchi Antonio Cherubini George Christoff Derek K Chu Alvaro A Cruz Dejan Dokic Yehia El-Gamal Motohiro Ebisawa Bernadette Eberlein John Farrell Montserrat Fernandez-Rivas Wytske J Fokkens Joao A Fonseca Yadong Gao Gaëtan Gavazzi Radolslaw Gawlik Asli Gelincik Bilun Gemicioğlu Maia Gotua Olivier Guérin Tari Haahtela Karin Hoffmann-Sommergruber Hans Jürgen Hoffmann Maja Hofmann Martin Hrubisko Madda lenaIllario Carla Irani Zhanat Ispayeva Juan Carlos Ivancevich Kaja Julge Igor Kaidashev Musa Khaitov Edward Knol Helga Kraxner Piotr Kuna Violeta Kvedariene Antti Lauerma Lan Tt Le Vincent Le Moing Michael Levin Renaud Louis Olga Lourenco Vera Mahler Finbarr C Martin Andrea Matucci Branislava Milenkovic Stéphanie Miot Emma Montella Mario Morais-Almeida Charlotte G Mortz Joaquim Mullol Leyla Namazova-Baranova Hugo Neffen Kristof Nekam Marek Niedoszytko Mikaëla Odemyr Robyn E O'Hehir Yoshitaka Okamoto Markus Ollert Oscar Palomares Nikolaos G Papadopoulos Petr Panzner Gianni Passalacqua Vincenzo Patella Mirko Petrovic Oliver Pfaar Nhân Pham-Thi Davor Plavec Todor A Popov Marysia T Recto Frederico S Regateiro Jacques Reynes Regina E Roller-Winsberger Yves Rolland Antonino Romano Carmen Rondon Menachem Rottem Philip W Rouadi Nathalie Salles Boleslaw Samolinski Alexandra F Santos Faradiba Sarquis Serpa Joaquin Sastre Jos M G A Schols Nicola Scichilone Anna Sediva Mohamed H Shamji Aziz Sheikh Isabel Skypala Sylwia Smolinska Milena Sokolowska Bernardo Sousa-Pinto Milan Sova Rafael Stelmach Gunter Sturm Charlotte Suppli Ulrik Ana Maria Todo-Bom Sanna Toppila-Salmi Ioanna Tsiligianni Maria Torres Eva Untersmayr Marilyn Urrutia Pereira Arunas Valiulis Joana Vitte Alessandra Vultaggio Dana Wallace Jolanta Walusiak-Skorupa De-Yun Wang Susan Waserman Arzu Yorgancioglu Osman M Yusuf Mario Zernotti Mihaela Zidarn Tomas Chivato Cezmi A Akdis Torsten Zuberbier Ludger Klimek

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz, and Center for Rhinology and Allergology, Wiesbaden, Germany.

Older adults, especially men and/or those with diabetes, hypertension and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritised to receive COVID-19 vaccines due to high risk of death. In very rare instances,the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society)Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
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http://dx.doi.org/10.1111/all.14838DOI Listing
April 2021

Abundance of Microvascular Endothelial Cells Is Associated with Response to Chemotherapy and Prognosis in Colorectal Cancer.

Cancers (Basel) 2021 Mar 23;13(6). Epub 2021 Mar 23.

Roswell Park Comprehensive Cancer Center, Department of Surgical Oncology, Buffalo, NY 14263, USA.

The generation of pathologic, immature, and dysfunctional vessels by angiogenesis is a mechanism of metastasis that has been a therapeutic target for colorectal cancer (CRC). In this study, we investigated the clinical relevance of intra-tumoral microvascular endothelial (mvE) cells in CRC using the xCell algorithm on transcriptome. A total of 1244 CRC patients in discovery and validation cohorts were analyzed. We found that an abundance of mvE cells did not mirror angiogenesis but reflected mature blood vessels because it was significantly associated with a high expression of vascular stability-related genes, including sphingosine-1-phosphate receptor genes and pericytes. Epithelial-mesenchymal transition and myogenesis gene sets were enriched in mvE cell abundant CRC, while mvE cell-less CRC enriched cell proliferation, oxidative phosphorylation, and protein secretion gene sets. mvE cell abundant CRC was associated with infiltration of M2 macrophages, dendritic cells, and less gamma-delta T cells (all < 0.001), but not with the interferon-γ response. mvE cell abundant CRC was significantly associated with worse patient survival in CRC. Interestingly, mvE cell abundant CRC was significantly associated with a high response rate to chemotherapy ( = 0.012) and worse patient survival for those that did not receive chemotherapy. However, there was no survival difference in patients who underwent chemotherapy. In conclusion, we estimated the abundance of mvE cells using the xCell algorithm on tumor transcriptome finding its association with the number of mature blood vessels in a tumor microenvironment and its ability to predict response to chemotherapy, thereby patient survival in CRC.
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http://dx.doi.org/10.3390/cancers13061477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004880PMC
March 2021

Grafting Methionine on 1F1 Ab Increases the Broad-Activity on HA Structural-Conserved Residues of H1, H2, and H3 Influenza a Viruses.

Evol Bioinform Online 2021 16;17:11769343211003082. Epub 2021 Mar 16.

School of Biotechnology, International University, Ho Chi Minh City, Vietnam.

A high level of mutation enables the influenza A virus to resist antibiotics previously effective against the influenza A virus. A portion of the structure of hemagglutinin HA is assumed to be well-conserved to maintain its role in cellular fusion, and the structure tends to be more conserved than sequence. We designed peptide inhibitors to target the conserved residues on the HA surface, which were identified based on structural alignment. Most of the conserved and strongly similar residues are located in the receptor-binding and esterase regions on the HA1 domain In a later step, fragments of anti-HA antibodies were gathered and screened for the binding ability to the found conserved residues. As a result, Methionine amino acid got the best docking score within the -2.8 Å radius of Van der Waals when it is interacting with Tyrosine, Arginine, and Glutamic acid. Then, the binding affinity and spectrum of the fragments were enhanced by grafting hotspot amino acid into the fragments to form peptide inhibitors. Our peptide inhibitor was able to form in silico contact with a structurally conserved region across H1, H2, and H3 HA, with the binding site at the boundary between HA1 and HA2 domains, spreading across different monomers, suggesting a new target for designing broad-spectrum antibody and vaccine. This research presents an affordable method to design broad-spectrum peptide inhibitors using fragments of an antibody as a scaffold.
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http://dx.doi.org/10.1177/11769343211003082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975486PMC
March 2021

Therapeutic Drug Monitoring is Necessary for Patients Receiving Posaconazole Tablet.

J Infect 2021 Mar 29. Epub 2021 Mar 29.

Department of Pharmacy, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.03.021DOI Listing
March 2021

Overexpression of MYBL2 predicts poor prognosis and promotes oncogenesis in endometrial carcinoma.

Eur J Histochem 2021 Mar 30;65(2). Epub 2021 Mar 30.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province.

Endometrial cancer (EC) is the most common gynecologic malignancy and still remains clinically challenging. We aimed to explore the potential biomarkers of EC and provide a theoretical basis for early screening and targeted therapy. The available transcriptome data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes. Immunohistochemistry was performed to detect gene expression. We analyzed the associations of MYBL2 with clinicopathological features and survival time and the biological effect of MYBL2 on the proliferation of EC cells. The effect of MYBL2 silencing on the transcriptome of EC cell model was analyzed by RNA-Seq. MYBL2 was significantly upregulated with obvious copy number alteration (CNA) in EC. Copy number amplification significantly increased MYBL2 mRNA expression, which led to a poor prognosis and severe pathological types of EC. Additionally, MYBL2 silencing significantly inhibited proliferation and induced apoptosis and G1-phase cell cycle arrest in EC cell lines. Our results indicate that MYBL2 is closely related to the cell cycle and apoptosis pathways in EC. The findings in this study provide evidence that MYBL2 can serve as a new candidate prognostic marker and a target for future therapeutic intervention in EC.
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http://dx.doi.org/10.4081/ejh.2021.3226DOI Listing
March 2021

The interactive effects of the seawater intrusion-affected zones and types of waterways on the surface water quality from the coastal Tien Giang Province, Vietnam.

Environ Monit Assess 2021 Mar 25;193(4):224. Epub 2021 Mar 25.

HUTECH Institute of Applied Sciences, Ho Chi Minh City University of Technology (HUTECH), 475A Dien Bien Phu, Ward 25, Binh Thanh District, Ho Chi Minh City, Vietnam.

Although inland surface water bodies have been studied intensively, few studies have looked at the interactive effects of seawater intrusion and waterway types on the water quality. The current study aimed to (1) assess the inland water quality as affected by waterway types and seawater intrusion-affected zones, (2) examine the longitudinal dynamics of the water quality, and (3) quantify the contributive percentage of pollution sources in the coastal Tien Giang Province, Vietnam. A total of 680 surface-water samples were taken from 34 sites distributed over the Tien River and its tributary canals from 2015 to 2019. The water samples were analyzed for 16 physical, chemical, and biological parameters, which were used for water quality index (WQI) estimation and subjected to two-way ANOVA and principal component analysis/factor analysis (PCA/FA). The WQI in both waterway types tended to get better from the downstream to the upstream zone with an improving rate of WQI faster in the River (from 79 to 88) than in the canals (from 82 to 85). The PCA/FA showed that water from the two waterway types could be polluted by six main pollution sources, one of which was derived from the seawater intrusion, one from aquaculture, and the others from agricultural, residential, and industrial activities. In brief, the inland surface water quality of a coastal area was interactively influenced by spatial distance and waterway types, transferring various pollutants in and out of the inland area.
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http://dx.doi.org/10.1007/s10661-021-09015-zDOI Listing
March 2021

Thermosensitive quaternized chitosan hydrogel scaffolds promote neural differentiation in bone marrow mesenchymal stem cells and functional recovery in a rat spinal cord injury model.

Cell Tissue Res 2021 Mar 24. Epub 2021 Mar 24.

Clinical Medical College, Yangzhou University , Jiangyang Middle Road No. 136, Yangzhou, Jiangsu Province, China.

A thermosensitive quaternary ammonium chloride chitosan/β-glycerophosphate (HACC/β-GP) hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) transfected with an adenovirus containing the glial cell-derived neurotrophic factor (GDNF) gene (Ad-rGDNF) was applied to spinal cord injury (SCI) repair. The BMSCs from rats were transfected with Ad-rGDNF, resulting in the expression of GDNF mRNA in the BMSCs increasing and their spontaneous differentiation into neural-like cells expressing neural markers such as NF-200 and GFAP. After incubation with HACC/β-GP hydrogel scaffolds for 2 weeks, neuronal differentiation of the BMSCs was confirmed using immunofluorescence (IF), and the expression of GDNF by the BMSCs was detected by Western blot at different time points. MTT assay and scanning electron microscopy confirmed that the HACC scaffold provides a non-cytotoxic microenvironment that supports cell adhesion and growth. Rats with SCI were treated with BMSCs, BMSCs carried by the HACC/β-GP hydrogel (HACC/BMSCs), Ad-rGDNF-BMSCs, or Ad-rGDNF-BMSCs carried by the hydrogel (HACC/GDNF-BMSCs). Animals were sacrificed at 2, 4, and 6 weeks of treatment. IF staining and Western blot were performed to detect the expression of NeuN, NF-200, GFAP, CS56, and Bax in the lesion sites of the injured spinal cord. Upon treatment with HACC/BMSCs, NF200 and GFAP were upregulated but CS56 and Bax were downregulated in the SCI lesion site. Furthermore, transplantation of HACC/GDNF-BMSCs into an SCI rat model significantly improved BBB scores and regeneration of the spinal cord. Thus, HACC/β-GP hydrogel scaffolds show promise for functional recovery in spinal cord injury patients.
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http://dx.doi.org/10.1007/s00441-021-03430-xDOI Listing
March 2021

Putting a dollar value on eating disorders: What is next?: Commentary on Streatfeild et al. (2021).

Int J Eat Disord 2021 Mar 24. Epub 2021 Mar 24.

School of Health and Social Development, Deakin Health Economics, Institute for Health Transformation, Deakin University, Geelong, Australia.

Eating disorders (EDs) have been associated with economic and quality of life burden. Several cost-of-illness studies has been reported, however, the study by Streatfeild et al. (2021) for the first time provided a comprehensive analysis of the economic burden of EDs in the United States. This study provides an opportunity to highlight the critical need for evaluating effectiveness and cost-effectiveness of preventive and treatment interventions for EDs. However, to be able to do, this further enhancement and inclusion of EDs into population health surveillance and health services data are required. While there were some limitations in the cost-of-illness study undertaken by Streatfeild et al. (2021), it does nonetheless present very reasonable recommendations as to what is required next. We agree that the likely impacts and costs of EDs are substantive and there is certainly a strong case for further research investment in this traditionally underinvested area.
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http://dx.doi.org/10.1002/eat.23507DOI Listing
March 2021

Diagnostic Patterns of Non-Small-Cell Lung Cancer at Princess Margaret Cancer Centre.

Curr Oncol 2020 Oct 1;27(5):244-249. Epub 2020 Oct 1.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

: Accurate classification of lung cancer subtypes has become critical in tailoring lung cancer treatment. Our study aimed to evaluate changes in diagnostic testing and pathologic subtyping of advanced non-small-cell lung cancer (NSCLC) over time at a major cancer centre. : In a review of patients diagnosed with advanced NSCLC at Princess Margaret Cancer Centre between 2007-2009 and 2013-2015, diagnostic method, sample type and site, pathologic subtype, and use of immunohistochemistry (IHC) staining and molecular testing were abstracted. : The review identified 238 patients in 2007-2009 and 283 patients in 2013-2015. Over time, the proportion of patients diagnosed with adenocarcinoma increased to 73.1% from 60.9%, and diagnoses of NSCLC not otherwise specified (NOS) decreased to 6.4% from 18.9%, < 0.0001. Use of diagnostic bronchoscopy decreased (26.9% vs. 18.4%), and mediastinal sampling procedures, including endobronchial ultrasonography, increased (9.2% vs. 20.5%, = 0.0001). Use of IHC increased over time to 76.3% from 41.6% ( < 0.0001). Larger surgical or core biopsy samples and those for which IHC was performed were more likely to undergo biomarker testing (both < 0.01). : Customizing treatment based on pathologic subtype and molecular genotype has become key in treating patients with advanced lung cancer. Greater accuracy of pathology diagnosis is being achieved, including through the routine use of IHC.
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http://dx.doi.org/10.3747/co.27.5757DOI Listing
October 2020

A multicenter study of three-dimensional echocardiographic evaluation of normal pediatric left ventricular volumes and function.

Echocardiography 2021 Mar 8. Epub 2021 Mar 8.

Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Three-dimensional echocardiography (3DE) evaluation of left ventricular (LV) volume and function in pediatrics compares favorably with cardiac magnetic resonance imaging. The aim of this study was to establish from a multicenter, normal pediatric z-score values of 3DE left ventricular volumes and function.

Methods: Six hundred and ninety-eight healthy children (ages 0-18 years) were recruited from five centers. LV 3DE was acquired from the 4-chamber view. A vendor-independent software analyzed end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using semi-automated quantification. Body surface area (BSA)-based z-scores were generated. Intraobserver and interobserver variability were calculated using intraclass correlation (ICC) and repeatability coefficient (RC).

Results: Z-scores were generated for ESV, EDV, and SV. The ICC for intraobserver variability for EDV, ESV, and SV was 0.99, 0.99, and 0.99, respectively. The ICC for interobserver variability for EDV, ESV, and SV was 0.98, 0.94, and 0.98, respectively. The RC for intraobserver and interobserver variability for LV EF was 4.39% (95% CI: 3.01, 5.59) and interobserver was 7.08% (95%CI: 5.51, 8.42).

Conclusions: We report pediatric z-scores for normal LV volumes using the semi-automated method from five centers, enhancing its generalizability. 3DE evaluation of LV volumes and EF in pediatric patients is highly reproducible.
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http://dx.doi.org/10.1111/echo.15026DOI Listing
March 2021

Association Between M235T and Left Ventricular Mass in Vietnamese Patients Diagnosed With Essential Hypertension.

Front Cardiovasc Med 2021 19;8:608948. Epub 2021 Feb 19.

Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.

Increasing left ventricular mass in hypertensive patients is an independent prognostic marker for adverse cardiovascular outcomes. Genetic factors have been shown to critically affect left ventricular mass. M235T is one of the genetic polymorphisms that may influence left ventricular mass due to its pivotal role in the regulation of plasma angiotensinogen level as well as hypertension pathophysiology in Asian populations. Currently, how M235T affects left ventricular mass is not well-described in Vietnamese hypertensive patients. This study aimed to investigate the association between M235T and left ventricular mass in Vietnamese patients diagnosed with essential hypertension. M235T genotyping and 2D echocardiography were performed on 187 Vietnamese subjects with essential hypertension. All the ultrasound parameters were obtained to calculate the left ventricular mass index according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging 2015 guidelines. Other clinical characteristics were also recorded, including age, gender, duration of hypertension, hypertensive treatment, lifestyle, renal function, fasting plasma glucose, and lipid profile. MT and TT genotypes were determined in 30 and 157 subjects, respectively. M235T genotype, duration of hypertension, body mass index, and ejection fraction statistically affected the left ventricular mass index, which was significantly greater in TT compared to MT carriers after adjusting for confounding factors. The TT genotype of M23T was associated with greater left ventricular mass in Vietnamese patients diagnosed with essential hypertension.
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http://dx.doi.org/10.3389/fcvm.2021.608948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933009PMC
February 2021

Na and/or Cl Toxicities Determine Salt Sensitivity in Soybean ( (L.) ), Mungbean ( (L.) R. Wilczek), Cowpea ( (L.) ), and Common Bean ( L.).

Int J Mol Sci 2021 Feb 14;22(4). Epub 2021 Feb 14.

School of Agriculture and Environment, The University of Western Australia, Perth, WA 6009, Australia.

Grain legumes are important crops, but they are salt sensitive. This research dissected the responses of four (sub)tropical grain legumes to ionic components (Na and/or Cl) of salt stress. Soybean, mungbean, cowpea, and common bean were subjected to NaCl, Na salts (without Cl), Cl salts (without Na), and a "high cation" negative control for 57 days. Growth, leaf gas exchange, and tissue ion concentrations were assessed at different growing stages. For soybean, NaCl and Na salts impaired seed dry mass (30% of control), more so than Cl salts (60% of control). All treatments impaired mungbean growth, with NaCl and Cl salt treatments affecting seed dry mass the most (2% of control). For cowpea, NaCl had the greatest adverse impact on seed dry mass (20% of control), while Na salts and Cl salts had similar intermediate effects (~45% of control). For common bean, NaCl had the greatest adverse effect on seed dry mass (4% of control), while Na salts and Cl salts impaired seed dry mass to a lesser extent (~45% of control). NaCl and Na salts (without Cl) affected the photosynthesis () of soybean more than Cl salts (without Na) (50% of control), while the reverse was true for mungbean. Na salts (without Cl), Cl salts (without Na), and NaCl had similar adverse effects on of cowpea and common bean (~70% of control). In conclusion, salt sensitivity is predominantly determined by Na toxicity in soybean, Cl toxicity in mungbean, and both Na and Cl toxicity in cowpea and common bean.
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http://dx.doi.org/10.3390/ijms22041909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918652PMC
February 2021

Barriers to accessing opioid substitution treatment for opioid use disorder: A systematic review from the client perspective.

Drug Alcohol Depend 2021 Apr 26;221:108651. Epub 2021 Feb 26.

School of Health and Social Development, Deakin University, 221 Burwood Highway, Burwood, Victoria, 3125, Australia. Electronic address:

Objectives: To update the existing evidence to identify specific barriers to initiation of opioid substitution therapy (OST) for those with opioid use disorder (OUD).

Methods: The review follows Preferred Reporting Items for Systematic Reviews andMeta-Analyses (PRISMA) guidelines. Six databases were initially searched in November 2019, with the search updated on 11 November 2020, for qualitative or quantitative studies reporting the barriers to initiating OST from the client with OUD perspective. Thematic analysis of the barriers to OST was undertaken to determine barrier themes and subthemes.

Results: There were 37 studies included in the review; 18 were qualitative, 15 were quantitative and four were mixed methods. The barrier themes identified were stigma and fear, regulatory, logistical, attitudinal and social factors. Within these barrier themes 19 barrier subthemes were identified. The most reported OST barrier subthemes were negative treatment perceptions, cost, stigma and lack of flexibility.

Conclusion: This review discusses important barriers to OST and examines reported barriers from the client perspective. OST guidelines and programs would benefit by introducing programs that reduce stigma, increase treatment knowledge and health literacy, reduce treatment costs, increase treatment flexibility and allow for easier treatment access.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108651DOI Listing
April 2021

Three-dimensional periodontal investigations using a prototype handheld ultrasound scanner with spatial positioning reading sensor.

Med Ultrason 2021 Mar 3. Epub 2021 Mar 3.

Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada School of Dentistry, University of Alberta, Edmonton, AB, Canada.

Aim: To demonstrate the feasibility of the 3D ultrasound periodontal tissue reconstruction of the lateral area of a porcine mandible using standard 2D ultrasound equipment and spatial positioning reading sensors.

Material And Method: Periodontal 3D reconstructions were performed using a free-hand prototype based on a 2D US scanner and a spatial positioning reading sensor. For automated data processing, deep learning algorithms were implemented and trained using semi-automatically seg-mented images by highly specialized imaging professionals.

Results: US probe movement analysis showed that non-parallel 2D frames were acquired during the scanning procedure. Comparing 3 different 3D periodontal reconstructions of the same porcine mandible, the accuracy ranged between 0.179 mm and 0.235 mm.

Conclusion: The present study demonstrated the diagnostic potential of 3D reconstruction using a free-hand 2D US scanner with spatial positioning readings. The use of auto-mated data processing with deep learning algorithms makes the process practical in the clinical environment for assessment of periodontal soft tissues.
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http://dx.doi.org/10.11152/mu-2837DOI Listing
March 2021

Th2 cell infiltrations predict neoadjuvant chemotherapy response of estrogen receptor-positive breast cancer.

Gland Surg 2021 Jan;10(1):154-165

Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Background: High infiltration of Th2 is linked to breast cancer progression and metastasis through the induction of cytokine release and T-cell anergy. The estrogen receptor (ER)-positive subtype, which accounts for 70% of breast cancer, is known to respond less to neoadjuvant chemotherapy (NAC) due to its low potential for proliferation. We hypothesized that Th2 high tumors are highly proliferative, and thus more likely to respond to NAC in ER-positive breast cancer.

Methods: We obtained clinicopathological data and overall survival information on 1,069 breast cancer patients from The Cancer Genome Atlas (TCGA). Computational algorithms and CIBERSORT were used to estimate immune cell infiltration. Additionally, xCell was used for validation.

Results: Th2 high tumors did not consistently associate with an unfavorable immune cell composition and tumor immune microenvironment but were found to be significantly elevated in the cancer stage. Th2 high tumors also correlated with high Nottingham pathological grade, as well as with Ki-67 and proliferation score in ER-positive subtypes. High Th2 tumors achieved a pathological complete response (pCR) significantly higher in ER-positive breast cancer.

Conclusions: In conclusion, high levels of Th2 are associated with aggressive features of breast cancer. Th2 levels may be a biomarker in patient selection for NAC in ER-positive breast cancer.
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http://dx.doi.org/10.21037/gs-20-571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882347PMC
January 2021

Early palliative care and quality of dying and death in patients with advanced cancer.

BMJ Support Palliat Care 2021 Feb 22. Epub 2021 Feb 22.

Department of Supportive Care, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada

Objective: Early palliative care (EPC) in the outpatient setting improves quality of life for patients with advanced cancer, but its impact on quality of dying and death (QODD) and on quality of life at the end of life (QOL-EOL) has not been examined. Our study investigated the impact of EPC on patients' QODD and QOL-EOL and the moderating role of receiving inpatient or home palliative care.

Method: Bereaved family caregivers who had provided care for patients participating in a cluster-randomised trial of EPC completed a validated QODD scale and indicated whether patients had received additional home palliative care or care in an inpatient palliative care unit (PCU). We examined the effects of EPC, inpatient or home palliative care, and their interactions on the QODD total score and on QOL-EOL (last 7 days of life).

Results: A total of 157 caregivers participated. Receipt of EPC showed no association with QODD total score. However, when additional palliative care was included in the model, intervention patients demonstrated better QOL-EOL than controls (p=0.02). Further, the intervention by PCU interaction was significant (p=0.02): those receiving both EPC and palliative care in a PCU had better QOL-EOL than those receiving only palliative care in a PCU (mean difference=27.10, p=0.002) or only EPC (mean difference=20.59, p=0.02).

Conclusion: Although there was no association with QODD, EPC was associated with improved QOL-EOL, particularly for those who also received inpatient care in a PCU. This suggests a long-term benefit from early interdisciplinary palliative care on care throughout the illness.

Trial Registration Number: ClinicalTrials.gov Registry (#NCT01248624).
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http://dx.doi.org/10.1136/bmjspcare-2021-002893DOI Listing
February 2021

Nuclear trafficking of bacterial effector proteins.

Cell Microbiol 2021 Feb 18:e13320. Epub 2021 Feb 18.

Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia.

Bacterial pathogens can subvert host responses by producing effector proteins that directly target the nucleus of eukaryotic cells in animals and plants. Nuclear-targeting proteins are categorised as either: "nucleomodulins," which have epigenetic-modulating activities; or "cyclomodulins," which specifically interfere with the host cell cycle. Bacteria can deliver these effector proteins to eukaryotic cells via a range of strategies. Despite an increasing number of reports describing the effects of bacterial effector proteins on nuclear processes in host cells, the intracellular pathways used by these proteins to traffic to the nucleus have yet to be fully elucidated. This review will describe current knowledge about how nucleomodulins and cyclomodulins enter eukaryotic cells, exploit endocytic pathways and translocate to the nucleus. We will also discuss the secretion of nuclear-targeting proteins or their release in bacterial membrane vesicles and the trafficking pathways employed by each of these forms. Besides their importance for bacterial pathogenesis, some nuclear-targeting proteins have been implicated in the development of chronic diseases and even cancer. A greater understanding of nuclear-targeting proteins and their actions will provide new insights into the pathogenesis of infectious diseases, as well as contribute to advances in the development of novel therapies against bacterial infections and possibly cancer.
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http://dx.doi.org/10.1111/cmi.13320DOI Listing
February 2021

Subtypes of EGFR- and HER2-Mutant Metastatic NSCLC Influence Response to Immune Checkpoint Inhibitors.

Clin Lung Cancer 2021 Jan 7. Epub 2021 Jan 7.

Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Canada. Electronic address:

Introduction: The efficacy of immune checkpoint inhibitors (ICIs) is low among EGFR-mutated non-small-cell lung cancer (NSCLC), although prolonged responses have occasionally been reported. We investigated the association between mutation subtypes and ICI outcomes among HER2- and EGFR-mutated NSCLC.

Patients And Methods: This retrospective single-center study analyzed patients with EGFR- and HER2-mutated advanced NSCLC who received at least 1 cycle of ICI between 2013 and 2019. Patient characteristics, mutation subtype, and ICI outcomes.

Results: Among 48 patients with advanced NSCLC, 14 (29%) had HER2 mutations and 34 (71%) had EGFR mutations. EGFR mutations included 16 (47%) exon 19 deletion, 7 (21%) L858R, 5 (15%) uncommon, and 6 (18%) exon 20 insertion. Compared to EGFR-sensitizing mutations (ESMs), HER2 and EGFR exon 20 mutations were associated with a trend toward better response (respectively, ESM, HER2, and EGFR exon 20: 11%, 29%, and 50%; P = .07) and significantly better disease control rates (respectively, 18%, 57%, and 67%; P = .008). Compared to ESM, HER2 mutations (adjusted hazard ratio, 0.35; P = .02) and EGFR exon 20 mutations (adjusted hazard ratio, 0.37; P = .10 trend) were also associated with improved PFS. Programmed death ligand 1 (PD-L1) expression remained an independent predictor of PFS (adjusted hazard ratio, 0.42; 95% confidence interval, 0.23-0.76; P = .004). The 6-month PFS rates were 29% (HER2), 33% (EGFR exon 20), and 4% (ESM). ICIs were generally well tolerated in this population. Importantly, no immune-related toxicity was observed in 10 patients who received a tyrosine kinase inhibitor (TKI) as the immediate next line treatment after ICI.

Conclusion: HER2 and EGFR exon 20 mutations derive greater benefit from ICIs with comparable PFS to wild-type historical second/third-line unselected cohorts. ICIs remain a treatment option for this genomic subgroup, given the absence of approved targeted therapies for these rare mutations.
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http://dx.doi.org/10.1016/j.cllc.2020.12.015DOI Listing
January 2021

Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm).

Hum Genome Var 2021 Feb 4;8(1). Epub 2021 Feb 4.

Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.
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http://dx.doi.org/10.1038/s41439-021-00135-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862625PMC
February 2021

Adverse Events and Economic Burden Among Patients Receiving Systemic Treatment for Mantle Cell Lymphoma: A Real-World Retrospective Cohort Study.

Anticancer Res 2021 Feb;41(2):927-936

Health Economics and Outcomes Research, AstraZeneca, Gaithersburg, MD, U.S.A.

Background/aim: Limited published real-world data describe adverse events (AEs) among patients treated for mantle-cell lymphoma (MCL). The aim of this retrospective study was to describe treatment patterns, AEs, and associated healthcare costs.

Patients And Methods: Patients had two or more claims coded for MCL diagnosis, the first claim date (07/01/2012-05/31/2017) was the index date. Patients with pre-index MCL diagnosis or systemic treatment, or hematopoietic stem cell transplantation were excluded. Cohorts by regimen were followed for up to three lines of therapy.

Results: Patients (n=395; median age 72 years; 31% female) were observed over a total of 576 lines of therapy, the most common being bendamustine plus rituximab; rituximab monotherapy; R-CHOP; and ibrutinib. The most frequent AEs were hypertension (40.5%), anemia (37.7%), and infection (36.1%). However, hepatotoxicity ($19,645), stroke ($18,893), and renal failure ($9,037) were associated with the highest medical costs per patient per month.

Conclusion: Among patients receiving common systemic treatments for MCL, AEs occurred frequently; some imposed substantial inpatient care costs.
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http://dx.doi.org/10.21873/anticanres.14846DOI Listing
February 2021

A phase-1 trial of linsitinib (OSI-906) in combination with bortezomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma.

Leuk Lymphoma 2021 Jan 28:1-0. Epub 2021 Jan 28.

Princess Margaret Cancer Centre Ontario Cancer Institute, Toronto, Canada.

We report results of a phase-1 study evaluating the safety and anti-cancer activity of the small molecule insulin-like growth factor-1 receptor (IGF-1R) inhibitor, linsitinib combined with bortezomib, and dexamethasone in relapsed/refractory multiple myeloma. Nineteen patients were enrolled across four dose-escalation cohorts (75-150 mg bid). The maximum tolerated dose of linsitinib was 125 mg. The most frequent Grade 3/4 AEs occurring in ≥10% of patients were thrombocytopenia (53%), bone pain (26%), neutropenia (21%), diarrhea (14%), anemia (14%), rash (10%), and lung infection (10%). Study discontinuation due to treatment-related AEs was low (16%). Across all cohorts the ORR was 61% (95% CI: 28.9-75.6%). Three partial response or greater and one stable disease were observed in proteasome inhibitor (PI) refractory patients ( = 5). Median PFS was 7.1 months (95% CI: 3.6-NA). Linsitinib plus bortezomib and dexamethasone demonstrate a manageable safety profile while the clinical benefit particularly in PI refractory patients warrants further exploration.
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http://dx.doi.org/10.1080/10428194.2021.1876864DOI Listing
January 2021

G protein Coupled Receptor Kinase 5 Modifies the Nucleolar Stress Response Activated by Actinomycin D.

Biochem Cell Biol 2021 Jan 28. Epub 2021 Jan 28.

Roseman University of Health Sciences, 14435, Henderson, United States, 89014-2333;

G protein coupled receptor kinase 5 (GRK5) is localized within the nucleus to moderate functions such as DNA transcription, in addition to its localization at the plasma membrane. In this report, we show that GRK5 modifies the nucleolar stress response activated by the DNA polymerase inhibitor, Actinomycin D (ActD). We showed an increased sensitivity to the apoptotic effects of ActD on cervical HeLa and the breast cancer cell line MDA MB 231 with reduced GRK5 protein expressions. Furthermore, the rate of response to ActD varied between the two types of breast cancer cells tested, MDA MB 231 and MCF7 cells, since they have innate differences in GRK5 protein expressions. During the early ActD treatment period, GRK5 phosphorylates nucleophosmin (NPM1) at T199 before and during treatment. Phosphorylation at this site increases the ability of NPM1 to interact with p14ARFin vitro, which may affect p14ARF protein expression levels. Expression levels are lower in control shRNA transfected cells but higher in GRK5 shRNA transfected cells. Collectively, this suggests that GRK5 modifies the nucleolar stress response associated with ActD.
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http://dx.doi.org/10.1139/bcb-2020-0480DOI Listing
January 2021

An External Validation Study of the Oakland and Glasgow-Blatchford Scores for Predicting Adverse Outcomes of Acute Lower Gastrointestinal Bleeding in an Asian Population.

Gastroenterol Res Pract 2021 5;2021:8674367. Epub 2021 Jan 5.

Department of Gastroenterology, Hue Central Hospital, Vietnam.

Aims: This study is aimed at (1) validating the performance of Oakland and Glasgow-Blatchford (GBS) scores and (2) comparing these scores with the SALGIB score in predicting adverse outcomes of acute lower gastrointestinal bleeding (ALGIB) in a Vietnamese population.

Methods: A multicenter cohort study was conducted on ALGIB patients admitted to seven hospitals across Vietnam. The adverse outcomes of ALGIB consisted of blood transfusion; endoscopic, radiologic, or surgical interventions; severe bleeding; and in-hospital death. The Oakland and GBS scores were calculated, and their performance was compared with that of SALGIB, a locally developed prediction score for adverse outcomes of ALGIB in Vietnamese, based on the data at admission. The accuracy of these scores was measured using the area under the receiver operating characteristic curve (AUC) and compared by the chi-squared test.

Results: There were 414 patients with a median age of 60 (48-71). The rates of blood transfusion, hemostatic intervention, severe bleeding, and in-hospital death were 26.8%, 15.2%, 16.4, and 1.4%, respectively. The SALGIB score had comparable performance with the Oakland score (AUC: 0.81 and 0.81, respectively; = 0.631) and outperformed the GBS score (AUC: 0.81 and 0.76, respectively; = 0.002) for predicting the presence of any adverse outcomes of ALGIB. All of the three scores had acceptable and comparable performance for in-hospital death but poor performance for hemostatic intervention. The Oakland score had the best performance for predicting severe bleeding.

Conclusions: The Oakland and SALGIB scores had excellent and comparable performance and outperformed the GBS score for predicting adverse outcomes of ALGIB in Vietnamese.
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http://dx.doi.org/10.1155/2021/8674367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806364PMC
January 2021

Changes in the Amplitude of Low-Frequency Fluctuation in Patients With Lifelong Premature Ejaculation by Resting-State Functional MRI.

Sex Med 2021 Feb 20;9(1):100287. Epub 2021 Jan 20.

Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address:

Introduction: Dapoxetine is considered a first-line treatment for patients with lifelong premature ejaculation (PE), and current researches have showed with functional magnetic resonance imaging (fMRI) that patients with lifelong PE might have abnormal brain function, but differences in brain function before and after administration have not been reported.

Aim: The aim of this study was to determine some objective differences in brain function between patients with lifelong PE before and after administration and healthy individuals.

Methods: In this study, 17 patients with lifelong PE and 11 healthy controls underwent clinical assessments and resting-state fMRI examination. After 4 weeks of treatment with dapoxetine 30 mg as needed, patients with PE underwent the same fMRI examination again 3 hours after dapoxetine administration.

Main Outcome Measure: The data were preprocessed using a data processing assistant for resting-state fMRI, and voxelwise amplitude of low-frequency fluctuation (ALFF) maps was calculated to identify abnormal neural activity in the brain.

Results: (a) The ALFF of patients with PE was significantly lower in the bilateral hippocampus and thalamus and higher in the left fusiform and lingual gyrus than that of healthy controls; (b) decreased and increased ALFF in patients with PE recovered after dapoxetine administration.

Conclusion: We preliminarily identified the relevant sites by analyzing changes in the ALFF in patients with lifelong PE. Analyzing ALFF changes in the brain by resting-state fMRI is an effective method to study PE, and it might provide a reference for disease diagnosis and future research. Yubo M, Lianjia H, Cuiping M, et al. Changes in the Amplitude of Low-Frequency Fluctuation in Patients With Lifelong Premature Ejaculation by Resting-State Functional MRI. Sex Med 2021;9:100287.
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http://dx.doi.org/10.1016/j.esxm.2020.100287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930883PMC
February 2021

Review on Databases and Bioinformatic Approaches on Pharmacogenomics of Adverse Drug Reactions.

Pharmgenomics Pers Med 2021 13;14:61-75. Epub 2021 Jan 13.

School of Biotechnology, International University, Ho Chi Minh City, Vietnam.

Pharmacogenomics has been used effectively in studying adverse drug reactions by determining the person-specific genetic factors associated with individual response to a drug. Current approaches have revealed the significant importance of sequencing technologies and sequence analysis strategies for interpreting the contribution of genetic variation in developing adverse reactions. Advance in next generation sequencing and platform brings new opportunities in validating the genetic candidates in certain reactions, and could be used to develop the preemptive tests to predict the outcome of the variation in a personal response to a drug. With the highly accumulated available data recently, the in silico approach with data analysis and modeling plays as other important alternatives which significantly support the final decisions in the transformation from research to clinical applications such as diagnosis and treatments for various types of adverse responses.
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http://dx.doi.org/10.2147/PGPM.S290781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812041PMC
January 2021

Growth and Spatial Control of Murine Neural Stem Cells on Reflectin Films.

ACS Biomater Sci Eng 2020 03 22;6(3):1311-1320. Epub 2020 Jan 22.

Department of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States.

Stem cells have attracted significant attention due to their regenerative capabilities and their potential for the treatment of disease. Consequently, significant research effort has focused on the development of protein- and polypeptide-based materials as stem cell substrates and scaffolds. Here, we explore the ability of reflectin, a cephalopod structural protein, to support the growth of murine neural stem/progenitor cells (mNSPCs). We observe that the binding, growth, and differentiation of mNSPCs on reflectin films is comparable to that on more established protein-based materials. Moreover, we find that heparin selectively inhibits the adhesion of mNSPCs on reflectin, affording spatial control of cell growth and leading to a >30-fold change in cell density on patterned substrates. The described findings highlight the potential utility of reflectin as a stem cell culture material.
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http://dx.doi.org/10.1021/acsbiomaterials.9b00824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833438PMC
March 2020

Resting-state magnetoencephalography source magnitude imaging with deep-learning neural network for classification of symptomatic combat-related mild traumatic brain injury.

Hum Brain Mapp 2021 Jan 15. Epub 2021 Jan 15.

Radiology, Research, and Psychiatry Services, VA San Diego Healthcare System, San Diego, California, USA.

Combat-related mild traumatic brain injury (cmTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral disabilities in Veterans and active-duty military personnel. Accurate diagnosis of cmTBI is challenging since the symptom spectrum is broad and conventional neuroimaging techniques are insensitive to the underlying neuropathology. The present study developed a novel deep-learning neural network method, 3D-MEGNET, and applied it to resting-state magnetoencephalography (rs-MEG) source-magnitude imaging data from 59 symptomatic cmTBI individuals and 42 combat-deployed healthy controls (HCs). Analytic models of individual frequency bands and all bands together were tested. The All-frequency model, which combined delta-theta (1-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-80 Hz) frequency bands, outperformed models based on individual bands. The optimized 3D-MEGNET method distinguished cmTBI individuals from HCs with excellent sensitivity (99.9 ± 0.38%) and specificity (98.9 ± 1.54%). Receiver-operator-characteristic curve analysis showed that diagnostic accuracy was 0.99. The gamma and delta-theta band models outperformed alpha and beta band models. Among cmTBI individuals, but not controls, hyper delta-theta and gamma-band activity correlated with lower performance on neuropsychological tests, whereas hypo alpha and beta-band activity also correlated with lower neuropsychological test performance. This study provides an integrated framework for condensing large source-imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI. The all-frequency model offered more discriminative power than each frequency-band model alone. This approach offers an effective path for optimal characterization of behaviorally relevant neuroimaging features in neurological and psychiatric disorders.
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http://dx.doi.org/10.1002/hbm.25340DOI Listing
January 2021

NOTCH Signaling Controls Ciliary Body Morphogenesis and Secretion by Directly Regulating Nectin Protein Expression.

Cell Rep 2021 Jan;34(2):108603

Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Anatomy and Cell Biology, University of Kansas School of Medicine, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. Electronic address:

Anterior segment dysgenesis is often associated with cornea diseases, cataracts, and glaucoma. In the anterior segment, the ciliary body (CB) containing inner and outer ciliary epithelia (ICE and OCE) secretes aqueous humor that maintains intraocular pressure (IOP). However, CB development and function remain poorly understood. Here, this study shows that NOTCH signaling in the CB maintains the vitreous, IOP, and eye structures by regulating CB morphogenesis, aqueous humor secretion, and vitreous protein expression. Notch2 and Notch3 function via RBPJ in the CB to control ICE-OCE adhesion, CB morphogenesis, aqueous humor secretion, and protein expression, thus maintaining IOP and eye structures. Mechanistically, NOTCH signaling transcriptionally controls Nectin1 expression in the OCE to promote cell adhesion for driving CB morphogenesis and to directly stabilize Cx43 for controlling aqueous humor secretion. Finally, NOTCH signaling directly controls vitreous protein secretion in the ICE. Therefore, this study provides important insight into CB functions and involvement in eye diseases.
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http://dx.doi.org/10.1016/j.celrep.2020.108603DOI Listing
January 2021