bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma
Authors: Gray Steven G.
Published: May 2021

Background

The role of immunotherapy in cancer is now well-established, and therapeutic options such as checkpoint inhibitors are increasingly being approved in many cancers such as non-small cell lung cancer (NSCLC). Malignant pleural mesothelioma (MPM) is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Evidence from clinical trials of checkpoint inhibitors in this rare disease, suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer.

Main text

While the majority of studies currently focus on the established checkpoint inhibitors (CTLA4 and PD1/PDL1), there are many other potential checkpoints that could also be targeted. In this review I provide a synopsis of current clinical trials of immunotherapies in MPM, explore potential candidate new avenues that may become future targets for immunotherapy and discuss aspects of immunotherapy that may affect the clinical outcomes of such therapies in this cancer.

Conclusions

The current situation regarding checkpoint inhibitors in the management of MPM whilst encouraging, despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Additional studies are therefore required to further delineate and improve our understanding of both checkpoint inhibitors and the immune system in MPM. Moreover, many new potential checkpoints have yet to be studied for their therapeutic potential in MPM. All these plus the existing checkpoint inhibitors will require the development of new biomarkers for patient stratification, response and also for predicting or monitoring the emergence of resistance to these agents in MPM patients. Other potential therapeutic avenues such CAR-T therapy or treatments like oncolytic viruses or agents that target the interferon pathway designed to recruit more immune cells to the tumor also hold great promise in this hard to treat cancer.
Comparison of three different screw trajectories in osteoporotic vertebrae: a biomechanical investigation
Authors: Jarvers J.-S. , Schleifenbaum S. , Pfeifle C. , Oefner C. , Edel M. , von der Höh N. , Heyde C.-E.
Published: May 2021

Background

Pedicle screw insertion in osteoporotic patients is challenging. Achieving more screw-cortical bone purchase and invasiveness minimization, the cortical bone trajectory and the midline cortical techniques represent alternatives to traditional pedicle screws. This study compares the fatigue behavior and fixation strength of the cement-augmented traditional trajectory (TT), the cortical bone trajectory (CBT), and the midline cortical (MC).

Methods

Ten human cadaveric spine specimens (L1 - L5) were examined. The average age was 86.3 ± 7.2 years. CT scans were provided for preoperative planning. CBT and MC were implanted by using the patient-specific 3D-printed placement guide (MySpine®, Medacta International), TT were implanted freehand. All ten cadaveric specimens were randomized to group A (CBT vs. MC) or group B (MC vs. TT). Each screw was loaded for 10,000 cycles. The failure criterion was doubling of the initial screw displacement resulting from the compressive force (60 N) at the first cycle, the stop criterion was a doubling of the initial screw displacement. After dynamic testing, screws were pulled out axially at 5 mm/min to determine their remaining fixation strength.

Results

The mean pull-out forces did not differ significantly. Concerning the fatigue performance, only one out of ten MC of group A failed prematurely due to loosening after 1500 cycles (L3). Five CBT already loosened during the first 500 cycles. The mean displacement was always lower in the MC. In group B, all TT showed no signs of failure or loosening. Three MC failed already after 26 cycles, 1510 cycles or 2144 cycles. The TT showed always a lower mean displacement. In the subsequent pull-out tests, the remaining mean fixation strength of the MC (449.6 ± 298.9 N) was slightly higher compared to the mean pull-out force of the CBT (401.2 ± 261.4 N). However, MC (714.5 ± 488.0 N) were inferior to TT (990.2 ± 451.9 N).

Conclusion

The current study demonstrated that cement-augmented TT have the best fatigue and pull-out characteristics in osteoporotic lumbar vertebrae, followed by the MC and CBT. MC represent a promising alternative in osteoporotic bone if cement augmentation should be avoided. Using the patient-specific placement guide contributes to the improvement of screws’ biomechanical properties.
Knee pain trajectories over 18 months in non-Hispanic Black and non-Hispanic White adults with or at risk for knee osteoarthritis
Authors: Johnson Alisa J. , Vasilopoulos Terrie , Booker Staja Q. , Cardoso Josue , Terry Ellen L. , Powell-Roach Keesha , Staud Roland , Kusko Daniel A. , Addison Adriana S. , Redden David T. , Goodin Burel R. , Fillingim Roger B. , Sibille Kimberly T.
Published: May 2021

Background

Pain is the hallmark symptom of knee osteoarthritis (OA), and varies widely across individuals. Previous research has demonstrated both fluctuating and stable pain trajectories in knee OA using various time periods. Changes in pain assessed quarterly (i.e. 3-month intervals) in knee OA are relatively unknown. The current study aimed to investigate temporal variations in pain over a one and a half year period (18 months) based on quarterly characteristic pain assessments, and to examine differences in pain patterns by sociodemographic and baseline pain characteristics.

Methods

The sample included a prospective cohort of 188 participants (mean age 58 years; 63% female; 52% non-Hispanic Black) with or at risk for knee OA from an ongoing multisite investigation of ethnic/race group differences. Knee pain intensity was self-reported at baseline and quarterly over an18-month period. Baseline pain assessment also included frequency, duration, and total number of pain sites. Group-based trajectory modeling was used to identify distinct pain trajectories. Multinomial logistic regression was used to examine associations between sociodemographic characteristics, risk factors, and pain trajectory groups.

Results

Pain trajectories were relatively stable among a sample of adults with knee pain. Four distinct pain trajectories emerged in the overall sample, with the largest proportion of participants (35.1%) classified in the moderate-high pain group. There were significant relationships between age, education, income, ethnicity/race and trajectory group; with younger, less educated, lower income, and non-Hispanic Black participants had a greater representation in the highest pain trajectory group.

Conclusions

Pain remained stable across a one and a half-year period in adults with or at risk for knee osteoarthritis, based on quarterly assessments. Certain sociodemographic variables (e.g. ethnicity/race, education, income, age) may contribute to an increased risk of experiencing greater pain.
Determination of the factors affecting sexual violence against women in Turkey: a population-based analysis
Authors: Alkan Ömer , Tekmanlı Hasan Hüseyin
Published: May 2021

Background

Sexual violence is one of the most investigated types of violence by national and international decision makers. The purpose of this study was to detect the factors that affect sexual violence against women in Turkey.

Methods

In this study, a cross-sectional data set was employed from the survey titled the National Research on Domestic Violence against Women in Turkey, which was conducted by the Hacettepe University Institute of Population Studies. Binary logistic and probit regression analyses were used to determine the factors influential in women’s exposure to sexual violence.

Results

The findings obtained from the analyses indicated that women’s exposure to sexual violence was influenced by a variety of factors including region, age, level of education, employment status, health condition, marital status, number of children as well as exposure to physical, economic, and verbal abuse. In addition, it was determined that the level of education, employment status, drug use, infidelity and other variables related to the husband/partner of the women who participated in the survey affected the women’s exposure to sexual violence.

Conclusion

There remains a higher probability of exposure to sexual violence among women residing in rural and less developed regions. A decrease in the women’s level of education increased their probability of exposure to sexual violence. An increase in the women's age and an increase in the level of education of the women’s husbands/partners lowered the probability of their exposure to sexual violence. There was a higher probability of exposure to sexual violence among women who had experienced physical, economic, and verbal abuse.
Use of electronic pharmacy transaction data and website development to assess antibiotic use in nursing homes
Authors: Song Sunah , Wilson Brigid M. , Marek Joseph , Jump Robin L. P.
Published: May 2021

Background

In 2017, the Centers for Medicare and Medicaid Services required all long-term care facilities, including nursing homes, to have an antibiotic stewardship program. Many nursing homes lack the resources, expertise, or infrastructure to track and analyze antibiotic use measures. Here, we demonstrate that pharmacy invoices are a viable source of data to track and report antibiotic use in nursing homes.

Methods

The dispensing pharmacy working with several nursing homes in the same healthcare corporation provided pharmacy invoices from 2014 to 2016 as files formatted as comma separated values. We aggregated these files by aligning elements into a consistent set of variables and assessed the completeness of data from each nursing home over time. Data cleaning involved removing rows that did not describe systemic medications, de-duplication, consolidating prescription refills, and removing prescriptions for insulin and opioids, which are medications that were not administered at a regular dose or schedule. After merging this cleaned invoice data to nursing home census data including bed days of care and publicly available data characterizing bed allocation for each nursing home, we used the resulting database to describe several antibiotic use metrics and generated an interactive website to permit further analysis.

Results

The resultant database permitted assessment of the following antibiotic use metrics: days of antibiotic therapy, length of antibiotic therapy, rate of antibiotic starts, and the antibiotic spectrum index. Further, we created a template for summarizing data within a facility and comparing across facilities. https://sunahsong.shinyapps.io/USNursingHomes/.

Conclusions

Lack of resources and infrastructure contributes to challenges facing nursing homes as they develop antibiotic stewardship programs. Our experience with using pharmacy invoice data may serve as a useful approach for nursing homes to track and report antibiotic use.
Transjugular intrahepatic portosystemic shunt (TIPS) procedure: an assessment of the quality and readability of online information
Authors: Lim Sean-Tee J. M. , Kelly Martin , Selvarajah Logeswaran , Murray Michael , Scanlon Timothy
Published: May 2021

Purpose

Transjugular intrahepatic portosystemic shunt (TIPS) procedure is an established procedure carried out by interventional radiologists to achieve portal decompression and to manage the complications of portal hypertension. The aim of this study was to evaluate the quality and readability of information available online for TIPS procedure.

Methods

Websites were identified using the search terms “TIPS procedure”, “TIPSS procedure”, “transjugular intrahepatic portosystemic shunt procedure”, with the first 25 pages from the three most popular search engines (Google, Bing and Yahoo) being selected for evaluation with a total of 225. Each Website was grouped by authorship into one of five categories: (1) Physician, (2) Academic, (3) For-profit, (4) Non-profit (including government and public health), or (5) Other (discussion/social media). Readability of each Website was assessed using the Flesch-Reading Ease score, Flesch–Kincaid grade level, Gunning-Fog Index, Coleman–Liau and SMOG index. Quality was calculated using the DISCERN instrument, the Journal of the American Medical Association (JAMA) benchmark criteria and the presence of Health on the Net (HON) code certification.

Results

After disregarding duplicate and non-accessible Websites a total of 81 were included. The mean DISCERN score assessing the quality of information provided by Websites was “good” (59.3 ± 10.2) with adherence to the JAMA Benchmark being 54.3%. Websites with HON-code certification were statistically significantly higher in terms of DISCERN (p = 0.034) and JAMA scores (p = 0.003) compared to HON-code negative sites. The readability scores of Websites ranged from 10 to 12th grade across calculators. Thirty-two out of the 81 Websites were targeted towards patients (39.5%), 46 towards medical professionals (56.8%) and 3 were aimed at neither (3.7%). The medical professional aimed Websites were statistically significantly more difficulty to read across all readability formulas (all p < 0.001).

Conclusion

While quality of online information available to patients is “good”, the average readability for information on the internet for TIPS is set far above the recommended 7th-grade level. Academic Websites were of the highest quality, yet most challenging for the general public to read. These findings call for the production of high-quality and comprehensible content around TIPS procedure, where physicians can reliably direct their patients for information.
Identifying homeless population needs in the Emergency Department using Community-Based Participatory Research
Authors: Franco Andrew , Meldrum Jonathan , Ngaruiya Christine
Published: May 2021

Background

Annually 1.5 million Americans face housing insecurity, and compared to their domiciled counterparts are three times more likely to utilize the Emergency Department (ED). Community Based Participatory Research (CBPR) methods have been employed in underserved populations, but use in the ED has been limited. We employed CBPR in an urban American hospital with a primary goal of improved linkage to care, reduced ED recidivism, and improved homeless health care.

Methods

A needs analysis was performed using semi-structured individual interviews with participants experiencing homelessness as well as with stakeholders. Results were analyzed using principles of grounded theory. At the end of the interviews, respondents were invited to join the “CBPR team”. At CBPR team meetings, results from interviews were expounded upon and discussions on intervention development were conducted.

Results

Twenty-five stakeholders were interviewed including people experiencing housing insecurity, ED staff, inpatient staff, and community shelters and services. Three themes emerged from the interviews. First, the homeless population lack access to basic needs, thus management of medical needs must be managed alongside social ones. Second, specific challenges to address homeless needs in the ED include episodic care, inability to recognize housing insecurity, timely involvement of ancillary staff, and provider attitudes towards homeless patients affecting quality of care. Lastly, improved discharge planning and communication with outside resources is essential to improving homeless health and decreasing ED overutilization. A limitation of results is difficulty for participants experiencing homelessness to commit to regular CBPR meetings, as well as possible bias towards social networks influencing included stakeholders.

Conclusion

CBPR is a promising approach to address gaps in homeless health care as it provides a comprehensive view incorporating various critical perspectives. Key ED-based interventions addressing recidivism include improved identification of housing insecurity, reinforced relationships between ED and community resources, and better discharge planning.
Genome sequencing sheds light on the contribution of structural variants to Brassica oleracea diversification
Authors: Guo Ning , Wang Shenyun , Gao Lei , Liu Yongming , Wang Xin , Lai Enhui , Duan Mengmeng , Wang Guixiang , Li Jingjing , Yang Meng , Zong Mei , Han Shuo , Pei Yanzheng , Borm Theo , Sun Honghe , Miao Liming , Liu Di , Yu Fangwei , Zhang Wei , Ji Heliang , Zhu Chaohui , Xu Yong , Bonnema Guusje , Li Jianbin , Fei Zhangjun , Liu Fan
Published: May 2021

Background

Brassica oleracea includes several morphologically diverse, economically important vegetable crops, such as the cauliflower and cabbage. However, genetic variants, especially large structural variants (SVs), that underlie the extreme morphological diversity of B. oleracea remain largely unexplored.

Results

Here we present high-quality chromosome-scale genome assemblies for two B. oleracea morphotypes, cauliflower and cabbage. Direct comparison of these two assemblies identifies ~ 120 K high-confidence SVs. Population analysis of 271 B. oleracea accessions using these SVs clearly separates different morphotypes, suggesting the association of SVs with B. oleracea intraspecific divergence. Genes affected by SVs selected between cauliflower and cabbage are enriched with functions related to response to stress and stimulus and meristem and flower development. Furthermore, genes affected by selected SVs and involved in the switch from vegetative to generative growth that defines curd initiation, inflorescence meristem proliferation for curd formation, maintenance and enlargement, are identified, providing insights into the regulatory network of curd development.

Conclusions

This study reveals the important roles of SVs in diversification of different morphotypes of B. oleracea, and the newly assembled genomes and the SVs provide rich resources for future research and breeding.
RETRACTED ARTICLE: Targeting a novel LncRNA SNHG15/miR-451/c-Myc signaling cascade is effective to hamper the pathogenesis of breast cancer (BC) in vitro and in vivo
Authors: Du Jiang , Zhong Hong , Ma Binlin
Published: May 2021

Background

To our knowledge, LncRNA SNHG15 exerted its tumor-promoting effects to facilitate the development of breast cancer (BC), but there still needed more data to elucidate the potential underlying mechanisms.

Methods

We examined genes expression status by performing Real-Time qPCR and Western Blot analysis, and cellular functions, including cell proliferation, viability, apoptosis, mobility, were measured by using the CCK-8 assay, colony formation assay, trypan blue staining assay, flow cytometer (FCM), transwell assay and wound scratch assay, respectively. The predicted targeting sites in LncRNA SNHG15, miR-451 and c-Myc 3′UTR were validated by dual-luciferase reporter gene system assay. Finally, we established the tumor-bearing mice models, and the expression status, including its enrichment and cellular localization were examined by immunohistochemistry (IHC) assay.

Results

Our data indicated LncRNA SNHG15 upregulated c-Myc to facilitate BC progression by sponging miR-451 in a competing endogenous RNA (ceRNA)-dependent manner in vitro and in vivo. Specifically, LncRNA SNHG15 and c-Myc were upregulated, while miR-451 was downregulated in BC cells and clinical tissues, compared to their normal counterparts. In addition, miR-451 negatively correlated with LncRNA SNHG15 and c-Myc, and LncRNA SNHG15 was positively relevant to c-Myc in BC tissues. Next, we validated that LncRNA SNHG15 sponged miR-451 to upregulate c-Myc in BC cells. Further gain- and loss-of-function experiments evidenced that LncRNA SNHG15 promoted, while miR-451 inhibited malignant phenotypes, including cell proliferation, viability, migration, invasion and epithelial-mesenchymal transition (EMT) in BC cells. Interestingly, the inhibiting effects of LncRNA SNHG15 ablation on BC progression were abrogated by both silencing miR-451 and overexpressing c-Myc.

Conclusions

We concluded that targeting the LncRNA SNHG15/miR-451/c-Myc signaling cascade was novel to hamper BC progression, which broadened our knowledge in this field, and provided potential biomarkers for BC diagnosis and treatment.
Comparative assessment of LDL-C and VLDL-C estimation in familial combined hyperlipidemia using Sampson’s, Martin’s and Friedewald’s equations
Authors: Vargas-Vázquez Arsenio , Bello-Chavolla Omar Yaxmehen , Antonio-Villa Neftali Eduardo , Mehta Roopa , Cruz-Bautista Ivette , Aguilar-Salinas Carlos A.
Published: May 2021

Background

Sampson et al. developed a novel method to estimate very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) in the setting of hypertriglyceridemia. Familial Combined Hyperlipidemia (FCHL) is a common primary dyslipidemia in which lipoprotein composition interferes with LDL-C estimation. This study aimed to evaluate performance of LDL-C using this new method (LDL-S) compared with LDL-C estimated by Friedewald’s and Martin eq. (LDL-F, LDL-M) in FCHL.

Methods

Data were collected from 340 subjects with confirmed FCHL. Concordance for VLDL-C measured by ultracentrifugation and LDL-C estimated using these measures compared to Sampson’s, Martin’s and Friedewald’s equations was performed using correlation coefficients, root mean squared error (RMSE) and bias. Also, concordance of misclassified metrics according to LDL-C (< 70 and < 100 mg/dL) and Apo B (< 80 and < 65 mg/dL) thresholds were assessed.

Results

Sampson’s equation was more accurate (RMSE 11.21 mg/dL; R2 = 0.88) compared to Martin’s (RMSE 13.15 mg/dL; R2 = 0.875) and the Friedewald’s equation (RMSE 13.7 mg/dL; R2 = 0.869). When assessing performance according to LDL-C, Sampson’s had highest correlation and lowest RMSE compared to other equations (RMSE 19.99 mg/dL; R2 = 0.840). Comparing performance strength across triglyceride levels, Sampson’s showed consistently improved correlations compared to Martin’s and Friedewald’s formulas for increasing triglycerides and for the FCHL phenotype of mixed dyslipidemia. Sampson’s also had improved concordance with treatment goals.

Conclusions

In FCHL, VLDL-C and LDL-C estimation using Sampson’s formula showed higher concordance with lipid targets assessed using VLDL-C obtained by ultracentrifugation compared with Friedewald’s and Martin’s equations. Implementation of Sampson’s formula could improve treatment monitoring in FCHL.
Evaluation of fetal foramen ovale blood flow by pulsed Doppler ultrasonography combined with spatiotemporal image correlation
Authors: Tang Wenjuan , Luo Yuanchen , Zeng Shi , Zhou Jiawei , Xu Ganqiong , Yang Jianwen
Published: May 2021

Objective

The objective of this study was to determine fetal foramen ovale blood flow utilizing pulsed Doppler combined with spatiotemporal image correlation.

Methods

A cross-sectional study was performed in 440 normal fetuses between 20 and 40 weeks of gestation. In order to calculate foramen ovale blood flow, the foramen ovale flow velocity–time integral was obtained by pulsed Doppler ultrasonography, and the foramen ovale area was measured by using spatiotemporal image correlation rendering mode. Foramen ovale blood flow was calculated as the product of the foramen ovale area and the velocity–time integral.

Results

Gestational age-specific reference ranges are given for the absolute blood flow (ml/min) of foramen ovale, showing an exponential increase from 20 to 30 weeks of gestation, and a flat growth trend during the last trimester, while the weight-indexed flow (ml/min/kg) of foramen ovale decreased significantly. The median weight-indexed foramen ovale blood flow was 320.82 ml/min/kg (mean 319.1 ml/min/kg; SD 106.33 ml/min/kg).

Conclusions

The reference range for fetal foramen ovale blood flow was determined from 20 to 40 weeks of gestation. The present data show that the volume of foramen ovale blood flow might have a limited capacity to increase during the last trimester.
Validity of EQ-5D-5L health-related quality of life questionnaire in self-reported diabetes: evidence from a general population survey
Authors: Jankowska Agnieszka , Młyńczak Katarzyna , Golicki Dominik
Published: May 2021

Background

This study aimed to assess the validity of the EQ-5D-5L in respondents with self-reported diabetes coming from a representative general population survey.

Methods

2974 respondents from the general adult population of Poland, chosen with multi-stage random sampling, were surveyed with HRQoL instruments (EQ-5D-5L, EQ VAS, SF-12, EQ-5D-3L) and a screening question about diabetes. To obtain EQ-5D index values, we used country-specific Polish value sets. We compared the instruments in terms of the ceiling effect, discriminatory power and frequency of individual health states. We evaluated construct validity in terms of known-groups validity and convergent validity of EQ-5D-5L dimensions and index values with other HRQoL measures.

Results

In respondents with diabetes (n = 247), the percentage reporting 'no problems' with EQ-5D-3L was reduced by 34.5% with the use of EQ-5D-5L (from 14.2% to 9.3%, respectively). A significant improvement in informativity was noticed in mobility and pain/discomfort dimensions (a relative increase of 23.1% and 22.7%, respectively). Known-groups construct validity analysis confirmed prior hypotheses—index scores were higher in the following groups: younger respondents, males, those taking no medication or oral antidiabetic drugs, and respondents with higher levels of education. The convergence between related EQ-5D-5L and EQ-5D-3L or SF-6D dimensions was stronger than between unrelated dimensions. The Bland–Altman analysis showed a mean difference between EQ-5D-5L and EQ-5D-3L, SF-6D, EQ VAS/100 index scores of 0.047, 0.165 and 0.231 respectively.

Conclusions

Our results support the validity of the EQ-5D-5L descriptive system and EQ-5D-5L index, based on the directly measured value set in respondents with self-reported diabetes coming from the general population.
Intercalary prosthetic replacement is a reliable solution for metastatic humeral shaft fractures: retrospective, observational study of a single center series
Authors: Zhao Zhiqing , Ye Zhipeng , Yan Taiqiang , Tang Xiaodong , Guo Wei , Yang Rongli
Published: May 2021

Background

Treatments for metastatic fracture of the humeral shaft continue to evolve as advances are made in both oncological and operative management. The purposes of this study were to critically evaluate the effectiveness of intercalary endoprostheses in treating metastatic humeral shaft fractures and to clarify the surgical indications for this technique.

Methods

Sixty-three patients treated surgically for 66 metastatic fractures of the humerus shaft were retrospectively reviewed. Intramedullary nailing (IMN) was performed in 16 lesions, plate fixation (PF) in 33 lesions, and prosthetic replacement in 17 lesions. The operative time, intraoperative blood loss, and postoperative complications were noted. The function of the upper extremities was assessed by the Musculoskeletal Tumor Society (MSTS) score and American Shoulder and Elbow Surgeons (ASES) score. All included patients were followed until reconstructive failure or death.

Results

The operative time was relatively shorter in the prosthesis group than in either the IMN group (p= 0.169) or PF group (p= 0.002). Notably, intraoperative blood loss was significantly less in the prosthesis group than in either the IMN group (p= 0.03) or PF group (p= 0.012). The average follow-up time was 20.3 (range, 3–75) months, and the overall survival rate was 59.7% at 12 months and 46.7% at 24 months. One rotator cuff injury, 3 cases of iatrogenic radial nerve palsy, 5 cases of local tumor progression, and 1 mechanical failure occurred in the osteosynthesis group, whereas one case of aseptic loosening of the distal stem and one case of local relapse were observed in the prosthesis group. There were no significant differences in functional scores among the three groups.

Conclusions

Intercalary prosthetic replacement of the humeral shaft may be a reliable solution for pathologic fractures patients; it is indicated for lesions with substantial bone loss, or accompanied soft tissue mass, or for those patients with better prognosis.
Diversifying the health workforce: a mixed methods analysis of an employment integration strategy
Authors: Baumann Andrea , Crea-Arsenio Mary , Ross Dana , Blythe Jennifer
Published: May 2021

Background

Historically, immigration has been a significant population driver in Canada. In October 2020, immigration targets were raised to an unprecedented level to support economic recovery in response to COVID-19. In addition to the economic impact on Canada, the pandemic has created extraordinary challenges for the health sector and heightened the demand for healthcare professionals. It is therefore imperative to accelerate commensurate employment of internationally educated nurses (IENs) to strengthen and sustain the health workforce and provide care for an increasingly diverse population. This study aimed to determine the effectiveness of a project to help job-ready IENs in Ontario, Canada, overcome the hurdle of employment by matching them with healthcare employers that had available nursing positions.

Methods

A mixed methods design was used. Interviews were held with IENs seeking employment in the health sector. Secondary analysis was conducted of a job bank database between September 1 and November 30, 2019 to identify healthcare employers with the highest number of postings. Data obtained from the 2016 Canadian Census were used to create demographic profiles mapping the number and proportion of immigrants living in the communities served by these employers. The project team met with senior executives responsible for hiring and managing nurses for these employers. The executives were given the appropriate community immigrant demographic profile, a manual of strategic practices for hiring and integrating IENs, and the résumés and bios of IENs whose skills and experience matched the jobs posted.

Results

In total, 112 IENs were assessed for eligibility and 95 met the inclusion criteria. Twenty-one healthcare employers were identified, and the project team met with 54 senior executives representing these employers. Ninety-five IENs were subsequently matched with an employer.

Conclusions

The project was successful in matching job-ready IENs with healthcare employers and increasing employer awareness of IENs' abilities and competencies, changing demographics, and the benefits of workforce diversity. The targeted activities implemented to support the project goal are applicable to sectors beyond healthcare. Future research should explore the long-term impact of accelerated employment integration of internationally educated professionals and approaches used by other countries.
The Herbst appliance and its modifications - prevalence and individuality
Authors: Karbach Mareike , Zöller Claudia , Zöller Georg , Wehrbein Heinrich , Erbe Christina
Published: May 2021

Objective

The aim of this study was to analyze the use of modified, cast splint Herbst appliances for the treatment of skeletal class II as an alternative to surgical bite correction over a period of five years.

Materials and methods

The patient cases all originate from the patients of the Department of Orthodontics at the University Medical Center of the Johannes Gutenberg University Mainz, Germany and the orthodontic practice Dres. Zöller, Kaiserslautern, Germany. Inclusion criteria were orthodontic treatment with the Herbst appliance and its modifications. The type of modification, number and frequency of the different modifications were determined on the basis of patient files, X-ray documents, photos and models.

Results

Of a total of 2881 new admissions over a period of five years, 1751 patients came from the Department of Orthodontics at the University Medical Center of the Johannes Gutenberg University Mainz and 1130 from the orthodontic practice in Kaiserslautern. A total of 336 patients were treated with a Herbst appliance during the period mentioned. 14 (13%) of the cases from the Herbst patient collective of the University Medical Center and 45 (19%) of the cases from the orthodontic practice were classified as modifications. The following modifications could be determined in descending order: University Medical Center Mainz: Herbst for anchorage during space closure (65%) > distalization (14%) ≥ bar construction as a space maintainer (14%) > Herbst applicance for anchoring for the adjustment of impacted teeth (7%); orthodontic practice Kaiserslautern: Herbst appliance with quadhelix in the maxilla (42%) > distalization (27%) > space closure (15%) > bar construction as a space maintainer (9%) > adjustment of impacted teeth (7%), multiple modifications occurred at 11%. The combination of quadhelix and Herbst appliance as well as multiple modifications have not yet been used in the University Medical Center Mainz. As an alternative to dysgnathia surgery, 23 adult patients (> 18 years) from the University Medical Center and 22 from the orthodontic practice were treated with a Herbst appliance.

Conclusion

Nearly 12% of Herbst appliances are used in everyday orthodontic practice and almost 18% of these are used with modification(s). The high anchoring quality and force-effect geometry of the Herbst appliance is suitable for combining and treating various other treatment tasks in addition to the classical treatment task of class II therapy.
The effects of different repair methods for a posterior root tear of the lateral meniscus on the biomechanics of the knee: a finite element analysis
Authors: Wang Jian-Yu , Qi Yan-Song , Bao Hu-Ri-Cha , Xu Yong-Sheng , Wei Bao-Gang , Wang Yong-Xiang , Ma Bing-Xian , Zhou Hui-Wen , Lv Fei
Published: May 2021

Purpose

To explore the impact of different repair methods for a lateral meniscus posterior root tear on the biomechanics of the knee joint using finite element analysis.

Methods

Finite element models of a healthy knee were established on the basis of MRI data from a volunteer using Mimics software, and the validity of the models was tested. The changes in the contact mechanics and kinematics of these finite element models under different repair approaches were then analyzed and compared.

Results

The normal meniscus had the maximum joint contact area, the minimum contact pressure, and the minimum contact stress. When total meniscectomy of the lateral meniscus was performed, the lateral compartment had the minimum joint contact area, the maximum contact pressure and the maximum contact stress. When complete avulsions of the posterior root of the lateral meniscus occurred, the maximum values of contact pressure and contact stress were between those of an intact meniscus and those of a meniscus treated with total meniscectomy. Lateral meniscal root attachment reconstruction by the single-stitch and double-stitch techniques resulted in a significant decrease in joint contact pressure and contact stress, leading to values comparable to those of a normal knee joint, and the double-stitch technique performed better than the single-stitch technique.

Conclusions

Repair surgery for lateral meniscal posterior root avulsions can effectively restore the contact mechanics and kinematics of the knee joint, and the double-stitch technique can result in better clinical outcomes than the single-stitch technique.
Angiotensin II upregulates RANKL/NFATC1 expression in synovial cells from patients with rheumatoid arthritis through the ERK1/2 and JNK pathways
Authors: Zhao Zhiping , Zhang Yongtao , Wang Changyao , Wang Xiangyu , Wang Yingzhen , Zhang Haining
Published: May 2021

Background

Angiotensin II (Ang II) is associated with rheumatoid arthritis (RA) development. The present study investigated the impact of Ang II on the expression of receptor activator of nuclear factor-κB ligand (RANKL), as well as of nuclear factor of activated T cells cytoplasmic 1 (NFATC1) in RA synovial cells, and explored the underlying mechanism.

Methods

The expression levels of RANKL, NFATC1, and Ang II type 1 receptor (AT1R) were analyzed by RT PCR, western-blot, and/or immunohistochemistry. Western blot was also used to analyze the p38MAPK, JNK, and ERK1/2 pathways.

Results

The expressions of RANKL and NFATC1 increased in synovial tissues of RA compared to osteoarthritis (OA) synovial tissues. The expression of RANKL was upregulated by Ang II, and this effect was mitigated by an AT1R blocker but not by an AT2R blocker. Furthermore, Ang II activated the ERK1/2, JNK, and p38MAPK pathways, and this effect was blocked by the AT1R blocker. However, ERK1/2 and JNK inhibitors, but not a p38MAPK inhibitor, blocked Ang II-induced RANKL expression. Ang II also increased the level of NFATC1, and this upregulation was attenuated by AT1R blockade, ERK1/2 and JNK inhibition, and siRNA-mediated RANKL silencing, but not by AT2R blockade or p38MAPK inhibition.

Conclusion

Our results indicated that Ang II activated the ERK1/2 and JNK pathways via AT1R, thus upregulating RANKL and NFATC1 expressions in RA synovial cells.
Tree diversity and carbon stocks in agroforestry systems in northern Ethiopia
Authors: Manaye Ashenafi , Tesfamariam Berihu , Tesfaye Musse , Worku Adefires , Gufi Yirga
Published: May 2021

Background

Agroforestry (AF) is an ancient tradition in Ethiopian dryland farming system. Several studies have examined system design, soil fertility management and system interactions, but the biodiversity and mitigation aspects of climate change have received less focus. We assessed the diversity of woody species, biomass carbon (C), and soil organic carbon (SOC) stock associated with indigenous dryland AF practices. A total of 197 smallholder farmers representing four AF practices (home garden, parkland, boundary plantation, and woodlot) from lowland, midland, and highland areas were systematically selected. The inventory of woody species was carried out on each farm's randomly formed plot.

Results

We identified a total of 59 woody species representing 48 genera and 32 families. Shannon diversity index (H') was highest in home garden and parkland AF, while woodlots had the highest mean total stock of biomass C (31 Mg C ha−1). C stocks for smallholding systems (total biomass C and SOC 0–60 cm) ranged from 77–135 Mg ha−1. Total biomass C stocks were significantly correlated with abundance (Spearman r = 0.333; p = 0.002) but biomass components were not significantly correlated with H'. SOC soil depth stock (0–60 cm) was positively and significantly associated with H' (Spearman r = 0.291 & 0.351; p < 0.01).

Conclusions

We report greater species richness in home garden and parkland AF systems than in woodlots. While parkland AF produce lower biomass and SOC stock relative to other AF systems. The strategic use of home gardens and boundary planting can improve tree diversity and carbon storage in Ethiopian dryland ecosystems.
Risk factors for transient and permanent congenital hypothyroidism: a population-based case-control study
Authors: Abbasi Fariba , Janani Leila , Talebi Malihe , Azizi Hosein , Hagiri Lotfali , Rimaz Shahnaz
Published: May 2021

Background

Congenital hypothyroidism (CH) is the most important cause of mental and physical retardation in newborns. The prevalence of CH has been reported high in East Azerbaijan province of Iran. However, the risk factors for CH are poorly understood. This study aimed to determine and compare risk factors for permanent and transient CH in East Azerbaijan, Iran.

Methods

A case-control study was conducted in the Iranian national screening program for CH. This study included 680 neonates: 340 neonates with confirmed CH and 340 matched healthy controls born at the same period and from the same residential area as the cases. Multiple logistic regression analyses were used to estimate the crude and adjusted odds ratios and 95% confidence intervals for the association between different risk factors and transient and permanent CH.

Results

Out of the 680 participants, 364 (53.53%) were male. Family history of CH (OR = 5.09, 95% CI: 1.66–15.63), neonatal jaundice (OR = 3.89, 95% CI: 2.36–6.43) and parental consanguineous relation (OR = 2.19, 95% CI: 1.51–3.17) were associated with an increased risk of permanent CH. Likewise, the use of Betadine in pregnancy (OR = 4.87, 95% CI: 1.45–16.28), family history of CH (OR = 5.98, 95% CI: 2.04–17.48), neonatal jaundice (OR = 2.81, 95% CI: 1.75–4.52), parental consanguineous relation (OR = 3.86, 95% CI: 1.92–5.74), and gestational age at birth (OR = 3.2, 95% CI: 1.90–5.41) were identified as risk factors for transient CH.

Conclusion

Family history, neonatal jaundice, gestational age at birth, and Betadine usage in pregnancy are associated with CH.
Intergenic RNA mainly derives from nascent transcripts of known genes
Authors: Agostini Federico , Zagalak Julian , Attig Jan , Ule Jernej , Luscombe Nicholas M.
Published: May 2021

Background

Eukaryotic genomes undergo pervasive transcription, leading to the production of many types of stable and unstable RNAs. Transcription is not restricted to regions with annotated gene features but includes almost any genomic context. Currently, the source and function of most RNAs originating from intergenic regions in the human genome remain unclear.

Results

We hypothesize that many intergenic RNAs can be ascribed to the presence of as-yet unannotated genes or the “fuzzy” transcription of known genes that extends beyond the annotated boundaries. To elucidate the contributions of these two sources, we assemble a dataset of more than 2.5 billion publicly available RNA-seq reads across 5 human cell lines and multiple cellular compartments to annotate transcriptional units in the human genome. About 80% of transcripts from unannotated intergenic regions can be attributed to the fuzzy transcription of existing genes; the remaining transcripts originate mainly from putative long non-coding RNA loci that are rarely spliced. We validate the transcriptional activity of these intergenic RNAs using independent measurements, including transcriptional start sites, chromatin signatures, and genomic occupancies of RNA polymerase II in various phosphorylation states. We also analyze the nuclear localization and sensitivities of intergenic transcripts to nucleases to illustrate that they tend to be rapidly degraded either on-chromatin by XRN2 or off-chromatin by the exosome.

Conclusions

We provide a curated atlas of intergenic RNAs that distinguishes between alternative processing of well-annotated genes from independent transcriptional units based on the combined analysis of chromatin signatures, nuclear RNA localization, and degradation pathways.
geneshot: gene-level metagenomics identifies genome islands associated with immunotherapy response
Authors: Minot Samuel S. , Barry Kevin C. , Kasman Caroline , Golob Jonathan L. , Willis Amy D.
Published: May 2021

Researchers must be able to generate experimentally testable hypotheses from sequencing-based observational microbiome experiments to discover the mechanisms underlying the influence of gut microbes on human health. We describe geneshot, a novel bioinformatics tool for identifying testable hypotheses based on gene-level metagenomic analysis of WGS microbiome data. By applying geneshot to two independent previously published cohorts, we identify microbial genomic islands consistently associated with response to immune checkpoint inhibitor (ICI)-based cancer treatment in culturable type strains. The identified genomic islands are within operons involved in type II secretion, TonB-dependent transport, and bacteriophage growth.
SANCDB: an update on South African natural compounds and their readily available analogs
Authors: Diallo Bakary N’tji , Glenister Michael , Musyoka Thommas M. , Lobb Kevin , Tastan Bishop Özlem
Published: May 2021

Background

South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/) is the sole and a fully referenced database of natural chemical compounds of South African biodiversity. It is freely available, and since its inception in 2015, the database has become an important resource to several studies. Its content has been: used as training data for machine learning models; incorporated to larger databases; and utilized in drug discovery studies for hit identifications.

Description

Here, we report the updated version of SANCDB. The new version includes 412 additional compounds that have been reported since 2015, giving a total of 1012 compounds in the database. Further, although natural products (NPs) are an important source of unique scaffolds, they have a major drawback due to their complex structure resulting in low synthetic feasibility in the laboratory. With this in mind, SANCDB is, now, updated to provide direct links to commercially available analogs from two major chemical databases namely Mcule and MolPort. To our knowledge, this feature is not available in other NP databases. Additionally, for easier access to information by users, the database and website interface were updated. The compounds are now downloadable in many different chemical formats.

Conclusions

The drug discovery process relies heavily on NPs due to their unique chemical organization. This has inspired the establishment of numerous NP chemical databases. With the emergence of newer chemoinformatic technologies, existing chemical databases require constant updates to facilitate information accessibility and integration by users. Besides increasing the NPs compound content, the updated SANCDB allows users to access the individual compounds (if available) or their analogs from commercial databases seamlessly.

Graphic abstract
In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease
Authors: Schollhammer Romain , Lepreux Sébastien , Barthe Nicole , Vimont Delphine , Rullier Anne , Sibon Igor , Berard Xavier , Zhang Andrea , Kimura Yasuyuki , Fujita Masahiro , Innis Robert B. , Zanotti-Fregonara Paolo , Morgat Clément
Published: May 2021

Background

Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [11C]-PBR28 and [18F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [18F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [18F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [11C]-PBR28.

Results

All in vitro sections showed specific binding of [18F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [11C]-PBR28 or [18F]-PBR06 was negative in all participants.

Conclusion

Despite good uptake on surgical samples in vitro, [11C]-PBR28 and [18F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease.

Trial registration: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov.
Correction to: Purification and characterization of thermoactive serratiopeptidase from Serratia marcescens AD-W2
Authors: Chander Devtulya , Khosla Jasmine Kour , Koul Diksha , Hossain Md. Mehedi , Dar Mohd Jamal , Chaubey Asha
Published: May 2021

An amendment to this paper has been published and can be accessed via the original article.