bluuebunny/crossref_metadata_2025 huggingface dataset:
MODL-29. Molecular Landscape of a comprehensive panel of pediatric brain cancer Patient-derived orthotopic xenograft (PDOX) models inform unique targets for drug responsiveness
Authors: Braun Frank K , Brabetz Sebastian , Qi Lin , Du Yuchen , Kogiso Mari , Zhang Hui Yuan , Linday Holly , Teo Wanyee , Baxter Patricia , Su Jack M F , Adekunle Adesina , Goeun Bae , Powell Reid T , Parsons Donald W , Chintagumpala Murali , Stephan Clifford C , Pfister Stefan , Lau Ching C , Kool Marcel , Li Xiao-Nan
Published: June 2022

Brain tumor is a leading cause of cancer related death in children. In addition to replicating histopathology, animal models faithfully replicating genetic/epigenetic abnormalities, molecular subtypes and broad inter-tumoral heterogeneities are needed. Through direct implantation of patient surgical or autopsied tumor tissues into matching locations in the brains of SCID mice, we developed a panel of 150 PDOX mouse models. Here, we report the analysis of 74 of the 150 PDOX models, 45 matching patient tissues and 60 non-tumorigenic samples to a well-annotated reference cohort of 2,801 methylation profiles of primary brain tumors. Our data showed that the lack of tumorigenicity was neither correlated with molecular subtypes nor predicted by low cell viabilities of the patient samples. Methylation profiling identified PDOX models representing nearly a full spectrum of molecular subtypes of pediatric brain tumors including GBM, medulloblastoma, ependymoma and ATRT. Direct comparison with the original patient tumors confirmed the replication of molecular subtypes. ONCOplot [FB1] analysis of PDOX models derived from matching pairs of primary and recurrent tumors (n=8) revealed close clustering with the patient tumors. Investigation of metastatic properties was performed in 13 MB models by harvesting and sub-transplanting matching PDOX primary tumors in the cerebella and metastatic tumors in the spinal cords. To confirm the potential and power of PDOX models in preclinical drug testing, we applied fractionated radiation (2 Gy/day x 5 days) and optimized multi-agent combinatory chemotherapies in MB models of the four major subgroups. High-throughput combination drug screening with ~ 8,000 drugs in PDOX-derived GBM cell lines and primary cultures of MB PDOX cells identified a library of ~ 3,500 drugs that were active in pediatric brain tumors. In summary, this study provides detailed information on molecular subclassification of a uniquely large cohort of PDOX models to serve as essential tools for brain tumor research.
RONC-16. Proton therapy for patients with embryonal tumor with multilayered rosettes in early childhood – results of the prospective KiProReg Study
Authors: Peters Sarah , Frisch Sabine , Merta Julien , Bäumer Christian , Blase Christoph , Tippelt Stephan , von Zezschwitz Barbara , Johann Pascal , von Hoff Katja , Geismar Dirk , Timmermann Beate
Published: June 2022

OBJECTIVES: Embryonal tumors with multilayered rosettes (ETMR) are rare malignancies of the central nervous system occurring predominantly in early childhood. Little is known about optimal time point and target volume of radiotherapy for the respective patients. The aim of this analysis was to evaluate treatment outcome in pediatric patients with ETMR treated with Proton Therapy (PT). METHODS: Between May 2016 and August 2021, 15 patients (9 male /6 female) with ETMR received PT in our institution and were enrolled in the prospective registry study KiProReg. Patient characteristics, treatment and outcome according to standardized follow-up data were descriptively analyzed by summarizing frequencies due to small sample size. RESULTS: Median age at PT was 3.0 years (range, 1.6-4.0 years). Three patients presented with metastatic disease (M1 n=1; M2 n=1; M2/3 n=1). Eight patients were treated with salvage PT at tumor progression or recurrence. Residual disease was present in three patients at start of PT. Tumor site was infratentorial (n=3) or supratentorial (n=12). All patients received Chemotherapy (CTX) prior to PT including high dose CTX (n=9) and intrathecal CTX (n=3). Concomitant CTX with temozolomide was administered in one patient. Patients received local PT (n=8) or craniospinal irradiation (CSI) followed by a local boost (n=7). Median dose was 54.0 Gy(RBE) (range, 3.6 -59.4 Gy(RBE)). PT was terminated prematurely in one patient due to cerebral edema and disease progression. Median follow-up after diagnosis was 16.3 months (range, 6.6-65.7 months) and 5.1 months (range, 0-62.4 months) after PT. Four patients treated for salvage experienced disease progression within three months after PT, three of them deceased. CONCLUSION: Preliminary results suggest promising outcomes for childhood ETMR after PT, especially in patients treated at initial diagnosis. Longer follow-up and larger cohorts are desirable to assess long-term survival and necessity of CSI.
Trends in Hospital Admissions for Chronic Obstructive Pulmonary Diseases After Comprehensive Tobacco Control Policies in Beijing, China
Authors: Wu Yiqun , Wang Zijing , Zheng Yunting , Wang Mengying , Wang Siyue , Wang Jiating , Wu Junhui , Wu Tao , Chang Chun , Hu Yonghua
Published: June 2022

Introduction

Only a few studies have examined the effectiveness of tobacco control policies on respiratory conditions, and the results were less consistent. The 2015 Beijing tobacco control policy package incorporating all six components of MPOWER has been implemented since Jun 2015. The present study aimed to evaluate the impact of a comprehensive tobacco control policy package on hospital admissions for chronic obstructive pulmonary disease (COPD) in Beijing, China.

Aims and Methods

An interrupted time-series study was conducted based on the hospital admission information for about 18 million residents, who were covered by the Beijing Medical Claim Data for Employees from January 2013 to June 2017. The average percentage change of COPD hospital admission rates and reductions in hospital admission numbers were estimated by segmented Poisson regression models.

Results

There were 54 040 COPD hospital admissions with a crude rate of 67.2 per 100 000 residents during the observational period. After the implementation of the policy package, the hospital admission rates of COPD were reduced by −14.7% (95%CI: −17.8%, −11.5%) immediately. The secular trend was slowed down by −3.0% (95% CI: −5.6%, −0.4%) annually. A total of 5 581 reductions in COPD hospital admissions were estimated during the 25 months post-law period, accounting for 17.5% (95% CI: 12.5%, 22.5%) of overall COPD hospital admissions. More reductions were shown in males and those aged over 65 years old.

Conclusions

The results indicated significant protections against hospitalization of COPD after the 2015 Beijing comprehensive tobacco control policy package. The results provide support for public health benefits for respiratory conditions from WHO-recommended tobacco control measures.

Implications

Only a few studies have examined the effectiveness of tobacco control policies on respiratory conditions, and the results were less consistent. Based on medical records for about 18 million residents, this study showed an association between comprehensive tobacco control policies and significant reductions of hospital admissions for chronic obstructive pulmonary disease. The results provide support for public health benefits for respiratory conditions from WHO-recommended tobacco control measures.
Modified Two-Tiered Testing Enzyme Immunoassay Algorithm for Serologic Diagnosis of Lyme Disease
Authors: Khan Farhan , Allehebi Ziyad , Shabi Yahya , Davis Ian , LeBlanc Jason , Lindsay Robbin , Hatchette Todd
Published: June 2022

The modified 2-tier testing algorithm (MTTT) for Lyme disease (LD) has been approved by the US Food and Drug Administration. In this study, we show that the MTTT detected 28% more cases of early infection compared with the standard 2-tier algorithm while retaining high specificity in a region with a high incidence of LD.
A Showcase of Igneous Processes in the Urumieh-Dokhtar Magmatic Arc: the Miocene-Quaternary Collisional Magmatism of the Bijar-Qorveh Area, Northwest Iran
Authors: Fedele Lorenzo , Rahimzadeh Bahman , Salari Giulia , Agostini Samuele , Masoudi Fariborz , Lustrino Michele
Published: June 2022

The Cenozoic Arabia–Iran continental collision was associated with emplacement of a large variety of magmatic rock types. This aspect is particularly evident in the Bijar-Qorveh area of NW Iran, where Miocene andesitic to rhyolitic rocks and Quaternary basic alkaline rocks crop out. The Miocene intermediate to acid products show radiogenic Sr and Pb isotopic compositions (87Sr/86Sri 0.70531–0.71109, 206Pb/204Pb 18.71–19.01, 207Pb/204Pb 15.66–15.73, 208Pb/204Pb 38.76–39.14), coupled with unradiogenic Nd isotopic ratios (143Nd/144Ndi 0.51223–0.51265). These characteristics, together with primitive mantle-normalised multielemental patterns resembling ‘subduction-related’ geochemical fingerprints, are considered ultimately derived from the Iranian plate mantle wedge, metasomatised during previous NE-directed Neothetyan Ocean subduction. The alkali-rich andesitic and dacitic rocks evidence both closed- and open-system differentiation, as typically observed for collisional settings in general. Both rock types display a high Sr/Y (37–100) and La/Yb (29–74) ‘adakitic’ signature that it is interpreted here with plagioclase (± amphibole) accumulation or melting of local mafic crustal rocks. Open-system processes involve recycling of crustal cumulates for pyroxene-rich andesite and biotite-rich dacite varieties and low-degree partial melting of the local crust for rhyolites. A radical change occurred during the Quaternary, when SiO2-understaturated to SiO2-saturated poorly evolved rocks (basanites, tephrites, alkaline and subalkaline basalts) were emplaced. The complete change of mantle sources suggests a phase of local extensional tectonics related with WNW-ESE right-transcurrent faults. The major oxide, as well as incompatible trace element and Sr-Nd-Pb isotopic fingerprint of these younger rocks is more akin to that of intraplate magmas, but still bearing some evidences for a variable contribution from a ‘subduction-modified’ mantle source. The NW-trend of increasing involvement of this subduction component is indicative of the strong tectonic control on magmatism. Additional lithotypes indicate the presence of open-system differentiation and remelting processes in the youngest phase of magmatic activity.
Effects of Trauma and Postmigration Stress on Refugee Women’s Health: A Life Course Perspective
Authors: Sangalang Cindy C , Vang Cindy , Kim Bum Jung , Harachi Tracy W
Published: June 2022

Trauma exposure and postmigration stress are associated with adverse health outcomes among refugees, yet the relative effect of these factors for subgroups of refugees and those resettled long-term remains unclear. Drawing on life course theory, this study evaluated the associations between war trauma, postmigration stress, and health among Southeast Asian refugee women in the United States, and whether these patterns differ across the life span. A community sample of Vietnamese and Cambodian refugee women aged 30–72 years (N = 293) reported mental and physical health outcomes, conflict-based trauma exposure, and postmigration measures of discrimination and community violence. Both trauma exposure and discrimination were associated with mental and physical health problems, with the relative effect of each stressor varying across specific health outcomes; community violence was associated with poorer mental health. Age moderated the effect of trauma exposure across health outcomes, with stronger associations between trauma and health for older women in particular. Findings provide support for the influence of trauma exposure and the importance of postmigration stressors on health across the life span for refugees. Attending to age group differences in the effects of these stressors, and to subgroups such as women, has implications for interventions addressing the long-term health of refugee populations.
Evaluation of In-Field Inoculation Methods for Characterization of Macadamia Germplasm to Husk Spot Incidence and Severity
Authors: Nunn Jasmine , Alam Mobashwer , Hardner Craig M. , Akinsanmi Olufemi A. , O’Connor Katie M. , De Faveri Joanne , Topp Bruce L.
Published: June 2022

Husk spot, a fungal disease of macadamia pericarps (Pseudocercospora macadamiae), induces premature abscission in several major commercial cultivars. Breeding for resistance to husk spot is a priority of the Australian macadamia industry. Due to the large tree size of macadamia and high numbers of progeny in breeding populations, inoculating for resistance screening is laborious and time consuming. Previously utilized methods included direct applications of P. macadamiae suspensions and the hanging of bags of diseased husks above developing fruit in tree canopies. In this study, both methods were modified to allow for efficient application in large-scale breeding populations, and their efficacy was evaluated. Two quantities of diseased husk per bag, ‘large’ (75 g) and ‘small’ (30 g), and two concentrations of sprayed P. macadamiae suspensions, ‘stock’ (5 × 105 propagules/ml) and ‘dilute’ (2.5 × 105 propagules/ml), were tested across two fruiting seasons. Treatments were compared against a control (sterile water) in commercial cultivars A38 and A4. Husk spot incidence and severity produced by small bags were significantly affected by season. A significant season effect was less common for other treatments. All four treatments infected over 50% of target fruit in each season, but the highest husk spot incidence across both seasons (≥85%) was produced from large bags. Overall, the large bags were the most reliable method for infection of target fruit. Results also demonstrate the importance of considering the effect of season when selecting husk spot inoculation methods.
Analysis of the Pathogenicity and Phylogeny of Colletotrichum Species Associated with Brown Blight of Tea (Camellia sinensis) in Taiwan
Authors: Lin Shiou-Ruei , Lin Ying-Hong , Ariyawansa Hiran A. , Chang Yu-Ching , Yu Si-Ying , Tsai Ichen , Chung Chia-Lin , Hung Ting-Hsuan
Published: June 2022

Brown blight, a destructive foliar disease of tea, has become a highly limiting factor for tea cultivation in Taiwan. To understand the population composition of the causal agents (Colletotrichum spp.), the fungal diversity in the main tea-growing regions all over Taiwan was surveyed from 2017 to 2019. A collection of 139 Colletotrichum isolates was obtained from 14 tea cultivars in 86 tea plantations. Phylogenic analysis using the ribosomal internal transcribed spacer, glutamine synthetase gene, Apn2-Mat1-2 intergenic spacer, β-tubulin, actin, calmodulin, and glyceraldehyde-3-phosphate dehydrogenase genes together with morphological characterization revealed three species associated with brown blight of tea; namely, Colletotrichum camelliae (95.6% of all isolates), C. fructicola (3.7%), and C. aenigma (0.7%). This is the first report of C. aenigma in Taiwan. The optimal growth temperatures were 25°C for C. camelliae and 25 and 30°C for C. fructicola and C. aenigma. Although C. fructicola and C. aenigma were more adapted to high temperature, C. camelliae was the most pathogenic across different temperatures. Regardless of whether spore suspensions or mycelial discs were used, significantly larger lesions and higher disease incidences were observed for wounded than for nonwounded inoculation and for the third and fourth leaves than for the fifth leaves. Wounded inoculation of detached third and fourth tea leaves with mycelial discs was found to be a reliable and efficient method for assessing the pathogenicity of Colletotrichum spp. within 4 days. Preventive application of fungicides or biocontrol agents immediately after tea pruning and at a young leaf stage would help control the disease.
RGDX1X2 motif regulates integrin αvβ5 binding for pluripotent stem cell adhesion
Authors: Yamada Yuji , Onda Toru , Hagiuda Ayami , Kan Ryuji , Matsunuma Masumi , Hamada Keisuke , Kikkawa Yamato , Nomizu Motoyoshi
Published: June 2022

The arginine‐glycine‐aspartic acid (RGD) motif is a cell adhesion sequence that binds to integrins. Some RGD‐containing peptides promote adhesion of both embryonic stem cells and induced pluripotent stem cells (iPSCs); however, not all such RGD‐containing peptides are active. In this study, we elucidated the role of RGD‐neighboring sequences on iPSC adhesion using diverse synthetic peptides and recombinant proteins. Our results indicate that iPSC adhesion requires RGDX1X2 sequences, such as RGDVF and RGDNY, and that the X1X2 residues are essential for the adhesion via integrin αvβ5 but not αvβ3. iPSCs express integrin αvβ5 but not αvβ3; therefore, iPSC adhesion requires the RGDX1X2‐containing sequences. The importance of the X1X2 residues was confirmed with both HeLa and A549 cells, which express integrin αvβ5 but not αvβ3. Analysis of RGD‐neighboring sequences provides important insights into ligand‐binding specificity of integrins. Identification of integrin αvβ5‐binding motifs is potentially useful in drug development, drug delivery, cell culture, and tissue engineering.
Experimental Pain Phenotype Profiles in Community-dwelling Older Adults
Authors: Wilson Abigail T. , Johnson Alisa J. , Laffitte Nodarse Chavier , Hoyos Lorraine , Lysne Paige , Peraza Julio A. , Montesino-Goicolea Soamy , Valdes-Hernandez Pedro A. , Somerville Jessie , Bialosky Joel E. , Cruz-Almeida Yenisel
Published: June 2022

Objectives:

Pain sensitivity and the brain structure are critical in modulating pain and may contribute to the maintenance of pain in older adults. However, a paucity of evidence exists investigating the link between pain sensitivity and brain morphometry in older adults. The purpose of the study was to identify pain sensitivity profiles in healthy, community-dwelling older adults using a multimodal quantitative sensory testing protocol and to differentiate profiles based on brain morphometry.

Materials and Methods:

This study was a secondary analysis of the Neuromodulatory Examination of Pain and Mobility Across the Lifespan (NEPAL) study. Participants completed demographic and psychological questionnaires, quantitative sensory testing, and a neuroimaging session. A Principal Component Analysis with Varimax rotation followed by hierarchical cluster analysis identified 4 pain sensitivity clusters (the “pain clusters”).

Results:

Sixty-two older adults ranging from 60 to 94 years old without a specific pain condition (mean [SD] age=71.44 [6.69] y, 66.1% female) were analyzed. Four pain clusters were identified characterized by (1) thermal pain insensitivity; (2) high pinprick pain ratings and pressure pain insensitivity; (3) high thermal pain ratings and high temporal summation; and (4) thermal pain sensitivity, low thermal pain ratings, and low mechanical temporal summation. Sex differences were observed between pain clusters. Pain clusters 2 and 4 were distinguished by differences in the brain cortical volume in the parieto-occipital region.

Discussion:

While sufficient evidence exists demonstrating pain sensitivity profiles in younger individuals and in those with chronic pain conditions, the finding that subgroups of experimental pain sensitivity also exist in healthy older adults is novel. Identifying these factors in older adults may help differentiate the underlying mechanisms contributing to pain and aging.
Molecular Mechanism of Sevoflurane Preconditioning Based on Whole-transcriptome Sequencing of Lipopolysaccharide-induced Cardiac Dysfunction in Mice
Authors: Xie Jiawei , Li Hongmei , Li Shuai , Li Jianling , Li Yalan
Published: June 2022

Sevoflurane, a widely used inhalation anesthetic, has been shown to be cardioprotective in individuals with sepsis and myocardial dysfunction. However, the exact mechanism has not been completely explained. In this study, we performed whole-transcriptome profile analysis in the myocardium of lipopolysaccharide-induced septic mice after sevoflurane pretreatment. RNA transcriptome sequencing showed that 97 protein coding RNAs (mRNAs), 64 long noncoding RNAs (lncRNAs), and 27 microRNAs (miRNAs) were differentially expressed between the lipopolysaccharide and S_L groups. Functional enrichment analysis revealed that target genes for the differentially expressed mRNAs between the 2 groups participated in protein processing in the endoplasmic reticulum, antigen processing and presentation, and the mitogen-activated protein kinase signaling pathway. The bioinformatics study of differentially expressed mRNAs revealed that 13 key genes including Hsph1, Otud1, Manf, Gbp2b, Stip1, Gbp3, Hspa1b, Aff3, Med12, Kdm4a, Gatad1, Cdkn1a, and Ppp1r16b are related to the heart or inflammation. Furthermore, the competing endogenous RNA network revealed that 3 of the 13 key genes established the lncRNA–miRNA–mRNA network (ENSMUST00000192774 --- mmu-miR-7a-5p --- Hspa1b, TCONS_00188587 --- mmu-miR-204-3p --- Aff3 and ENSMUST00000138273 --- mmu-miR-1954 --- Ppp1r16b) may be associated with cardioprotection in septic mice. In general, the findings identified 11 potential essential genes (Hsph1, Otud1, Manf, Gbp2b, Stip1, Gbp3, Hspa1b, Aff3, Med12, Kdm4a, Gatad1, Cdkn1a, and Ppp1r16b) and mitogen-activated protein kinase signaling pathway involved in sevoflurane-induced cardioprotection in septic mice. In particular, sevoflurane may prevent myocardial injury by regulating the lncRNA–miRNA–mRNA network, including (ENSMUST00000192774—mmu-miR-7a-5p—Hspa1b, TCONS_00188587—mmu-miR-204-3p—Aff3, and ENSMUST00000138273—mmu-miR-1954—Ppp1r16b networks), which may be a novel mechanism of sevoflurane-induced cardioprotection.
Analysis of the Reasons for the Discontinuation of Orthokeratology Lens Use: A 4-Year Retrospective Study
Authors: Ma Lina , Xu Man , Wang Jing , Niu Xiaoguang
Published: June 2022

Purpose:

Although orthokeratology has a positive effect on myopia control, some patients discontinue orthokeratology lens use. This study analyzed the data of all patients who had been fitted with an orthokeratology lens in the past 4 years and the reasons for discontinued lens use, with the aim of improving the prevention and control of myopia.

Methods:

This retrospective study analyzed the data of patients, aged 8 to 18 years, fitted with orthokeratology lenses from 2017 to 2020. The ametropic spherical lens powers ranged from −6.00 D to −0.75 D, and the cylindrical lens powers were all more than −1.50 D. The reasons for discontinuation of lens wear were analyzed and compared. The period of lens wear (median [range]) was 24 (13.5–34.5) months.

Results:

A total of 2,499 patients' files were retrieved. The duration of lens wear was 24 (13.5–34.5) months. A total of 50 patients discontinued lens use, including 25 patients (50.0%) who could not adhere to lens use for various reasons, nine patients (18.0%) with a short sleep time, eight patients (16.0%) with economic difficulties, and five patients (10.0%) who experienced a poor effect after wearing the lenses. Corneal infiltrates affected lens use in three patients (6.0%). In addition, 30 patients underwent surgical correction when they reached adulthood.

Conclusion:

Although orthokeratology lenses are effective and safe, there are still a small number of patients who discontinued lens use for various reasons. Adherence and precautions should be emphasized during the process.
Practicing gratitude to combat despair: Discovered joy in addictions nursing
Authors: Curtis Alexa Colgrove
Published: June 2022

The convergence of the opioid epidemic and COVID-19 pandemic created an urgent need in our communities to combat a rising tide of “deaths of despair.” Responding to the call to care for persons with a substance use disorder is a service to both community and to self. Working in addictions provides the nurse practitioner renewed opportunity to experience life and career affirming humility, resilience, and gratitude through the joys of recovery.
The Influence of the Introduction of Biologic Agents on Surgical Intervention in Paediatric Inflammatory Bowel Disease
Authors: Bethell George S. , Ashton James J. , Adams Stephen , Beattie R. Mark , Hall Nigel J. , Stanton Michael P.
Published: June 2022

Objectives:

To determine how the use of biological therapy is associated with surgical intervention for paediatric inflammatory bowel disease (PIBD) at a population level.

Methods:

Hospital Episode Statistics data were obtained for all admissions within England (1997–2015), in children aged 0–18 years, with an ICD-10 code for diagnosis of Crohn disease (CD), ulcerative colitis (UC), or inflammatory bowel disease-unclassified (IBD-U). Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures codes for major surgical resection associated with PIBD and for biological therapy were also obtained. Data are presented as median values (interquartile range).

Results:

In total, 22,645 children had a diagnosis of PIBD of which 13,722 (61%) had CD, 7604 (34%) had UC, and 1319 (5.8%) cases had IBD-U. Biological therapy was used in 4054 (17.9%) cases. Surgical resection was undertaken in 3212 (14%) cases, more commonly for CD than UC (17.5 vs 10.3%, P < 0.0001). Time from diagnosis to major surgical resection was 8.3 (1.2–28.2) months in CD and 8.2 (0.8–21.3) months in UC. As the time-frame of the dataset progressed, there was a decreased rate of surgical intervention (P = 0.04) and an increased use of biological therapy (P < 0.0001). Additionally, the number of new diagnoses of PIBD increased.

Conclusions:

The introduction of biologic agents has been associated with a reduction in cases undergoing surgery in children with a known diagnosis of PIBD. As time progresses we will be able to determine whether biological therapies prevent the need for surgery altogether or just delay this until adulthood.
Simulation-Based Mastery Learning to Facilitate Transition to Nursing Practice
Authors: Tan Kimberly-Ann Zi Ying , Seah Betsy , Wong Lai Fun , Lee Cindy Ching Siang , Goh Hongli Sam , Liaw Sok Ying
Published: June 2022

Background:

Simulation-based mastery learning (SBML) was developed and implemented to facilitate nursing students' transition to clinical practice.

Purpose:

To evaluate nursing students' perspectives on the impact of SBML on their transition to clinical practice.

Method:

A descriptive qualitative study using focus group discussions was conducted with final-year nursing students who had completed their clinical practicum and SBML.

Results:

Three themes emerged: authenticity of simulations, whereby students were able to draw some parallels between their simulations and clinical experiences; self-efficacy in clinical practice, which was gained through deliberate practice; and application of cognitive tools, which provided mental frameworks to guide clinical performances.

Conclusion:

This study highlights the need to ensure the fidelity of the simulations to achieve authentic experiences, provide deliberate practice to develop self-efficacy, and use cognitive tools for mental model formation to create a high-quality SBML program to foster better transfer of simulation learning to real-life setting.
Fitting of Orthokeratology in the United States: A Survey of the Current State of Orthokeratology
Authors: Lipson Michael J. , Curcio Louise R.
Published: June 2022

SIGNIFICANCE

The Fitting of Orthokeratology in the United States (FOKUS) survey provides information about the US orthokeratology market. This independent survey is the first to attain detailed assessment of the orthokeratology market.

PURPOSE

This study aimed to develop and administer a survey to eye care providers in the United States who are managing orthokeratology patients and those who are not, to determine a profile of prescribers, patients, and overall market.

METHODS

The FOKUS survey was administered and distributed online. Outcome measures of the FOKUS survey involved general categories of (1) practice and practitioner profiles, (2) clinical prescribing patterns, (3) patient profile, (4) products and marketing, (5) fees, and (6) market size and growth.

RESULTS

The number of eye care providers who are actively fitting and managing orthokeratology patients in the United States is approximately 3000. A total of 545 responded to the survey; 283 reported that they were actively fitting orthokeratology. Furthermore, 68% of respondents prescribed orthokeratology with the intent of managing myopia, 53% monitor axial length, and 61% start orthokeratology patients at 13 years or younger. The mean number of years a patient wears orthokeratology is 7.8 years. A commonly reported complication with orthokeratology is corneal staining. Microbial keratitis is rarely or never seen by 86% of respondents. Of those currently fitting, 56% anticipate growth of orthokeratology fitting over the next 12 months. Of those not currently fitting orthokeratology, 46% plan to start within 2 years.

CONCLUSIONS

Orthokeratology represents a small but growing segment of the US contact lens market. The number of practitioners actively prescribing and fitting orthokeratology in the United States is approximately 3000 with high potential for growth within the next 2 years. Results of the FOKUS survey are relevant to practitioners currently fitting or considering orthokeratology, manufacturers, educators, and researchers as baseline for future orthokeratology market assessment.
Impact of demographic factors on chronic pain among adults in the United States
Authors: Mullins Peter M. , Yong Robert J. , Bhattacharyya Neil
Published: June 2022

Introduction:

Chronic pain affects more than 1 in 5 American adults, and its effects are not evenly distributed throughout the population.

Methods:

Using the National Health Interview Survey (NHIS), a household-based annual survey of self-reported health status of U.S. adults, this cross-sectional study describes differences in the prevalence of chronic pain and its effects across socioeconomic groups.

Results:

In univariate analyses, chronic pain was more prevalent among female respondents, persons with lower educational attainment, non-Hispanic White individuals, and those who were insured as well as those who were married. After accounting for all other demographic factors, age, female sex, and lower educational attainment were associated with higher odds of having chronic pain, whereas Hispanic and non-Hispanic Black race were associated with lower odds. Despite lower odds of having chronic pain, Hispanic and non-Hispanic Black race were associated with greater odds of reporting more severe pain than White race. There were no significant differences across race in the effects of pain on life, work, or family, although female sex and lower educational attainment were associated with greater effects of pain on these domains. Educational attainment was the only characteristic associated with greater odds of ineffective pain management after accounting for all other demographic factors.

Conclusions:

Implications for reducing disparities in the treatment of chronic pain are discussed.
Pectoral Plane Block versus Local Anesthetic Infiltration in Breast Implant Augmentation Surgery: A Retrospective Study
Authors: Moris Vivien , Sanchez Antoine , Guilloteau Adrien , Guillier David , Heranney Julie , Zwetyenga Narcisse , Kerfant Nathalie
Published: June 2022

Background:

Pectoral plane blocks are routinely used in analgesia for patients undergoing dual-plane breast augmentation with implants. Local anesthetic infiltration is a simple alternative technique with the same aim. The authors evaluated both techniques.

Methods:

In this single-center retrospective study, patients received pectoral plane block (ropivacaine 0.2%, 10 ml for pectoral plane I; 20 ml for pectoral plane II) or local anesthetic infiltration. The primary outcome measure was pain, according to the visual analogue scale, at 24 hours after surgery. Secondary outcomes included the measure of pain at 1, 2, 6, and 12 hours after surgery; total opioid consumption at 24 hours; and opioid side effects.

Results:

Eighty-one patients were finally recruited: 37 in the pectoral plane group and 44 in the local anesthetic infiltration group. Patient characteristics were comparable between the two groups. At 24 hours after surgery, the local anesthetic infiltration group showed a decrease in pain, with a visual analogue scale score of 0.7 versus 1.5 in the pectoral plane group (p = 0.007). There was no difference in visual analogue scale score between the two groups at 1, 2, 6, or 12 hours after surgery. The duration of anesthesia was increased in the pectoral plane group, with 153 minutes versus 120 minutes in the local anesthetic infiltration group (p < 0.001). There was no difference in rescue morphine consumption between the two groups.

Conclusions:

The authors found that local anesthetic infiltration had a superior analgesic effect at 24 hours after surgery for dual-plane breast implant augmentation compared with pectoral plane block. These findings are a good indication that the local anesthetic infiltration technique is at least as effective as pectoral plane block while being safe, fast, and easy to use.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Brain abscess in immunocompetent patients: recent findings
Authors: Thy Michael , Gaudemer Augustin , d’Humières Camille , Sonneville Romain
Published: June 2022

Purpose of review

We conducted a systematic review of the literature to update findings on the epidemiology and the management of cerebral abscesses in immunocompetent patients.

Recent findings

Observational studies suggest that the overall prognosis has improved over the last decades but mortality rates remain high. Several parameters may contribute to a better prognosis, including the identification of common risk factors for brain abscess, the systematic use of brain MRI at diagnosis, the implementation of appropriate neurosurgical and microbiological techniques for diagnosis, the optimization of the antibacterial treatment based on epidemiology and pharmacokinetic/pharmacodynamic studies, and a long-term follow-up for detection of secondary complications. Outcome research on brain abscess is mainly based on observational studies. Randomized controlled trials have yet to be performed to identify clinically relevant interventions associated with improved patient-centered outcomes.

Our review highlights the importance of a multidisciplinary approach to optimize brain abscess management both at the acute phase and in the long-term. Randomized controlled studies are urgently needed to identify interventions associated with improved outcomes.
Barriers and Enablers of Second-Order Problem-Solving Behavior: How Nurses Can Break Away From the Workaround Culture
Authors: Vanbelleghem Sem , De Regge Melissa , Van Nieuwenhove Yves , Gemmel Paul
Published: June 2022

Background and Objectives:

Nurses are challenged by numerous day-to-day unexpected problems due to poorly performing work systems that hinder patient care. These operational failures persist in hospitals, partly because nurses tend to prefer quick fixes or workarounds over real improvements that prevent recurrence. The aim of this review is to shed light on the barriers to and enablers of nurses' second-order problem-solving behavior and their consequences, so that hospitals can learn from failure and improve organizational outcomes.

Methods:

We conducted a systematic review, with quantitative, qualitative, and mixed-method articles, searching 6 databases (PubMed, Embase, Web of Science, CINAHL, and Google Scholar) following the Preferred Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Quality assessment for inclusion was performed by 2 independent authors using the Mixed Methods Appraisal Tool (MMAT). A descriptive synthesis was used for analysis.

Results:

This study reveals the barriers and enablers for second-order problem-solving behavior, and synthesizes improvement proposals within 3 perspectives, namely the “empowerment” perspective, the “process improvement” perspective, and the “time” perspective. Furthermore, we found that limited attention is given to the patient's perspective, and the existence of a no-action behavior.

Conclusion:

Although operational failures have several important consequences for hospital staff and organizations, there has been hardly any research into the barriers and enablers that initiate second-order problem-solving behavior; stemming this nursing behavior has thus rarely appeared as a suggestion for improvement.
Diagnostic Agreement Among General Practitioners, Residents, and Senior Rheumatologists for Rheumatic Diseases
Authors: Farias Teixeira Maria Eugênia , Bonjorno Letícia Pastorelli , Menezes Pâmella Indira Silva Oliveira , Gigante Samara Libich Gusmão , Dib Saulo Musse , Oliveira Fabíola Reis , Silva Lucienir Maria , Petean Flávio Calil , Moraes Daniela Aparecida , Luppino-Assad Rodrigo , Oliveira Rodrigo , Almeida Sérgio Couto Luna , Oliveira Maria Carolina , Louzada-Junior Paulo , Oliveira Renê Donizeti Ribeiro
Published: June 2022

Objective

The aim of this study was to evaluate the concordance of the diagnoses made by senior rheumatologists and those made by residents in rheumatology and by general practitioners (GPs).

Methods

In this cohort, 497 patients referred by GPs from August 1, 2018 to December 16, 2019 were evaluated first by a second-year resident in rheumatology. After clinical rounds, the diagnoses by senior rheumatologists were assumed as the criterion standard and defined the prevalence of the rheumatic diseases, divided into 5 groups: rheumatoid arthritis, spondyloarthritis, other connective tissue diseases and vasculitis, nonautoimmune rheumatic diseases, and nonrheumatic diseases. The follow-up ended on November 30, 2020. We calculated sensibility, specificity, positive predictive value, negative predictive value, and κ coefficient of the diagnosis by GPs and residents.

Results

The diagnoses were changed for 58% of the referral letters. Diseases of low complexity, such as fibromyalgia and osteoarthritis, accounted for 50% of the diagnoses. Compared with senior rheumatologists, residents in rheumatology had κ > 0.6 for all the groups, whereas GPs had κ < 0.5, with the worst performance for nonautoimmune rheumatic disease (κ = −0.18) and nonrheumatic disease (κ = 0.15). In terms of level of complexity, 46% of the letters were inappropriate.

Conclusions

We found a poor level of diagnostic agreement between GPs and the rheumatology team. General practitioners had difficulties diagnosing and treating rheumatic diseases, referring patients that should be treated in the primary level of health care. One year of training in rheumatology made residents' skills comparable to those of senior rheumatologists.
Focusing on Patient-outcome performance measures of Active and Passive Implants – A Systematic Review
Authors: Stucke Jana , Tzvi-Minker Elinor , Keck Andreas
Published: June 2022

Motivation

Active implantable electronic medical devices are used in different fields of medicine, in particular cardiology and neurology. Several papers have been published over the years comparing the technical performance of implants between leading manufactures. However, no such comparison has been done with respect to “Patient-Reported Outcomes” (PROs) for most implant types, despite its importance in evaluating the quality of a medical device. With the recent update of the European Union’s (EU) regulation on public procurement towards value-based medicine, it has become beneficial for manufacturers to focus more on PROs to differentiate their products in order to create a marketing leverage. Most importantly, investigating PROs can assist shared decision-making, support pharmaceutical labelling claims and influence healthcare policy and practice. Due to this the review aims to showcase the lack of PRO comparisons between implant manufacturers across different medical fields and its impact on patients and surgeons.

Methods

A literature search was conducted for active and passive implant performance comparisons in the area of implantable cardioverter-defibrillator (ICDs), deep brain stimulation (DBS), cochlear implants (CIs) and intraocular lenses (IOLs). The search focused on the availability of manufacturer comparisons with regards to PROs. A total of 640 papers from 2000 until 2022 were screened in detail for the search term “patient reported outcomes” for the different implant types. Next, we analyzed the results by tagging papers based on the specific topics they investigated in their study to enable a cross-comparison. We noted whether the implant manufacturers were mentioned as well as whether a manufacturer comparison was done. Studies were also evaluated based on the number of patients included.

Results

A total of 38 papers were identified for ICDs, 31 for DBS, 68 for IOLs and 34 for CIs. 50% of the papers for IOL focused on PROs and 22% and 14% for CIs and DBS, whilst mentioning the manufacturers. No papers dealing with PROs could be identified for ICDs. Manufacturer comparison was not attempted by any of the reviewed papers, despite implants such as CIs and DBS having quite a significant impact on the quality of life.

Conclusions

There is an urgent need for clinical studies which focus on PRO comparisons between implants of different manufacturers, to not only provide physicians and patients with critical information that informs their decision prior to implantation, but also to increase the competition between manufacturers, thus, fostering innovation. The former would allow physicians to recommend the most suitable implant for the patient. In addition, this will drive manufacturers towards PRO focused improvements.
Identifying and managing problematic trials: a Research Integrity Assessment (RIA) tool for randomized controlled trials in evidence synthesis
Authors: Weibel Stephanie , Popp Maria , Reis Stefanie , Skoetz Nicole , Garner Paul , Sydenham Emma
Published: June 2022

Evidence synthesis findings depend on the assumption that the included studies follow good clinical practice and results are not fabricated or contain errors. Studies which are problematic due to scientific misconduct, poor research practice, or honest error may distort evidence synthesis findings. Authors of evidence synthesis need transparent mechanisms to identify and manage problematic studies to avoid misleading findings.

As evidence synthesis authors of the Cochrane COVID-19 review on ivermectin, we identified many problematic studies in terms of research integrity and regulatory compliance. Through iterative discussion, we developed a Research Integrity Assessment (RIA) tool for randomized controlled trials (RCTs). RIA was piloted and used in updating this Cochrane review. In this paper, we explain the rationale and application of the RIA tool.

RIA assesses six study criteria: study retraction, prospective trial registration, adequate ethics approval, plausible authorship, sufficient reporting of methods (e.g., randomization), and plausibility of study results. RIA was used in the Cochrane review as part of the eligibility check during screening of potentially eligible studies. Problematic studies were excluded and studies with open questions were held in awaiting classification until clarified. RIA decisions were made independently by two authors and reported transparently. Using the RIA tool resulted in the exclusion of >40% of studies in the first update of the review.

RIA is a complementary tool prior to assessing ‘Risk of Bias’ aiming to establish the integrity and authenticity of studies. RIA provides a platform for urgent development of a standard approach to identifying and managing problematic studies.
Whole Exome Sequencing Analyses Support a Role of Vitamin D Metabolism in Ischemic Stroke
Authors: Xie Yuhan , Acosta Julián N. , Ye Yixuan , Demarais Zachariah S. , Conlon Carolyn J. , Chen Ming , Zhao Hongyu , Falcone Guido J.
Published: June 2022

Ischemic stroke (IS) is a highly heritable trait. Genome-wide association studies have identified several commonly occurring susceptibility risk loci for this condition. However, there are limited data on the contribution of rare genetic variation to IS. We conducted a whole-exome association study of IS in 152,058 UK Biobank participants (mean age 57, 6.8 [SD 8.0], 83,131 [54.7%] were females), including 1,777 IS cases (mean age 61.4 [SD 6.6], 666 [37.5%] were females). We performed single-variant analyses for all variants and gene-based analyses for loss of function and deleterious missense rare variants. In the gene-based analysis, rare genetic variation at CYP2R1 was significantly associated with IS risk (P=2.6×10−6), exceeding the Bonferroni-corrected threshold for 16,074 tests (P<3.1 × 10−6). We first replicated these findings using summary statistics from a genome-wide association study that included 67,162 IS cases and 454,450 controls (gene-based test for CYP2R1, P=0.003). We pursued a second replication focused on IS recurrence using individual-level data from 1,706 IS survivors, including 142 cases of recurrent IS, enrolled in the VISP trial (gene-based test for CYP2R1, P=0.001). We also found that common genetic variation at CYP2R1 was associated with white matter hyperintensity volume (42,310 participants) and both mean diffusivity and fractional anisotropy (17,663 participants) in the subcohort of UK Biobank (all gene-based tests P<0.05). Because CYP2R1 plays an important role in vitamin D metabolism, our results support a role of this pathway in the occurrence of ischemic cerebrovascular disease.
Spatiotemporal and ontogenetic variation, microbial selection, and predicted antifungal function in the skin-associated microbiome of a Rocky Mountain amphibian
Authors: Goodwin Kenen B. , Hutchinson Jaren D. , Gompert Zachariah
Published: June 2022

Host-associated microbiomes play important roles in host health and pathogen defense. In amphibians, the skin-associated microbiome serves as an innate immune defense with potential implications for disease management. Few studies have examined season-long temporal variation in the amphibian skin-associated microbiome, and the interactions between bacteria and fungi on amphibian skin remain poorly understood. We characterize season-long temporal variation in the skin-associated microbiome of the western tiger salamander (Ambystoma mavortium) for both bacteria and fungi between sites and across salamander life stages. 207 skin-associated microbiome samples were collected from salamanders at two Rocky Mountain lakes throughout the summer and fall of 2018, and 127 additional microbiome samples were collected from lake water and lake substrate. We used 16S and ITS next-generation sequencing data with Bayesian Dirichlet-multinomial regression to estimate the relative abundances of bacterial and fungal taxa, test for differential abundance, examine microbial selection, and derive alpha and beta diversity. The antifungal function of bacterial communities was predicted using stochastic character mapping and a database of antifungal bacterial isolates. We examined microbial absolute abundances using Bayesian negative binomial LASSO coupled with synthetic gene spike-ins. For both bacteria and fungi, we observed variation in community composition through time, between sites, and with salamander age and life stage. We found salamander skin to be selective for microbes, with many taxa disproportionately represented relative to the environment, and we observed selection for predicted antifungal bacteria. Ultimately, this ecological knowledge may assist in the conservation of amphibian species threatened by chytridiomycosis and other emerging diseases.
A Big Data COVID-19 literature pattern discovery using NLP
Authors: Petousis Panayiotis , Stylianou Vasilis
Published: June 2022

As our collective knowledge about COVID-19 continues to grow at an exponential rate, it becomes more difficult to organize and observe emerging trends. In this work, we built an open source methodology that uses topic modeling and a pretrained BERT model to organize large corpora of COVID-19 publications into topics over time and over location. Additionally, it assesses the association of medical keywords against COVID-19 over time. These analyses are then automatically pushed into an open source web application that allows a user to obtain actionable insights from across the globe.