bluuebunny/crossref_metadata_2025 huggingface dataset:
Beliefs and barriers associated with COVID-19 vaccination among the general population in Saudi Arabia
Authors: Magadmi Rania M. , Kamel Fatemah O.
Published: July 2021

Background

Developing a vaccine against COVID-19 is considered a key strategy to end the pandemic. However, public acceptance is reliant on beliefs and perception toward the vaccine. Therefore, the study aimed to assess the beliefs and barriers associated with COVID-19 vaccination among the Saudi population.

Methods

An online self-administered questionnaire was distributed across the main regions of Saudi Arabia on May 2020. The questionnaire addressed the socio-demographic variables, beliefs toward COVID-19 vaccination, and potential barriers that may prevent participants from being vaccinated. The association between COVID-19 vaccine acceptance and sociodemographic variables were analyzed. Logistic regression analysis was used to identify the predicting variables of vaccine acceptance.

Results

Out of 3101 participants, 44.7% were accepting of COVID-19 vaccination if available, whereas 55.3% admitted hesitancy. Younger, male, who received seasonal influenza vaccine were more likely to accept taking the vaccine. The study found that concerns about side effects were the key barrier for vaccine acceptance. Furthermore, the majority of refusers may accept the vaccine if additional studies confirmed safety and effectiveness.

Conclusion

Results can be utilized in planning vaccination campaigns while waiting for vaccine development.
Exposure–safety analyses of nintedanib in patients with chronic fibrosing interstitial lung disease
Authors: Schmid Ulrike , Weber Benjamin , Sarr Celine , Freiwald Matthias
Published: July 2021

Background

Nintedanib reduces the rate of decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis-associated ILD (SSc-ILD). The recommended dose of nintedanib is 150 mg twice daily (BID).

Methods

Data from Phase II and III trials in IPF and Phase III trials in SSc-ILD and progressive fibrosing ILDs other than IPF were analyzed to investigate the relationship between nintedanib plasma concentrations (exposure) and safety (liver enzyme elevations [defined as transaminase elevations equal or greater than 3 times the upper limit of normal] and diarrhea).

Results

Using data from 1403 subjects with IPF treated with 50–150 mg nintedanib BID, a parametric time-to-first-event model for liver enzyme elevations was established. Besides exposure, gender was a significant covariate, with a three–fourfold higher exposure-adjusted risk in females than males. Subsequent analysis of combined data from IPF, SSc-ILD (n = 576) and progressive fibrosing ILD (n = 663) studies suggested a consistent exposure–liver enzyme elevation relationship across studies. No exposure–diarrhea relationship was found using data from the various fibrosing ILDs, but diarrhea risk was dependent on dose administered.

Conclusions

The positive correlation between exposure and risk of liver enzyme elevations was consistent across nintedanib studies in IPF, SSc-ILD and progressing fibrosing ILDs other than IPF. The effect size does not warrant a priori dose adjustment in patients with altered plasma exposure (excluding hepatic impairment patients, where there are specific labelling recommendations). For diarrhea, dose administered was a better predictor than exposure.
Medical Assistance in Dying in patients with advanced cancer and their caregivers: a mixed methods longitudinal study protocol
Authors: Li Madeline , Shapiro Gilla K. , Klein Roberta , Barbeau Anne , Rydall Anne , Bell Jennifer A. H. , Nissim Rinat , Hales Sarah , Zimmermann Camilla , Wong Rebecca K. S. , Rodin Gary
Published: July 2021

Background

The legal criteria for medical assistance in dying (MAiD) for adults with a grievous and irremediable medical condition were established in Canada in 2016. There has been concern that potentially reversible states of depression or demoralization may contribute to the desire for death (DD) and requests for MAiD. However, little is known about the emergence of the DD in patients, its impact on caregivers, and to what extent supportive care interventions affect the DD and requests for MAiD. The present observational study is designed to determine the prevalence, predictors, and experience of the DD, requests for MAiD and MAiD completion in patients with advanced or metastatic cancer and the impact of these outcomes on their primary caregivers.

Methods

A cohort of patients with advanced or metastatic solid tumour cancers and their primary caregivers will be recruited from a large tertiary cancer centre in Toronto, Ontario, Canada, to a longitudinal, mixed methods study. Participants will be assessed at baseline for diagnostic information, sociodemographic characteristics, medical history, quality of life, physical and psychological distress, attitudes about the DD and MAiD, communication with physicians, advance care planning, and use of psychosocial and palliative care interventions. Measures will subsequently be completed every six months and at the time of MAiD requests. Quantitative assessments will be supplemented by qualitative interviews in a subset of participants, selected using quota sampling methods.

Discussion

This study has the potential to add importantly to our understanding of the prevalence and determinants of the DD, MAiD requests and completions in patients with advanced or metastatic cancer and of the experience of both patients and caregivers in this circumstance. The findings from this study may also assist healthcare providers in their conversations about MAiD and the DD with patients and caregivers, inform healthcare providers to ensure appropriate access to MAiD, and guide modifications being considered to broaden MAiD legislation and policy.
Evaluating the implementation of a chronic obstructive pulmonary disease management program using the Consolidated Framework for Implementation Research: a case study
Authors: Paciocco Stefan , Kothari Anita , Licskai Christopher J. , Ferrone Madonna , Sibbald Shannon L.
Published: July 2021

Background

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic disease that requires comprehensive approaches to manage; it accounts for a significant portion of Canada’s annual healthcare spending. Interprofessional teams are effective at providing chronic disease management that meets the needs of patients. As part of an ongoing initiative, a COPD management program, the Best Care COPD program was implemented in a primary care setting. The objectives of this research were to determine site-specific factors facilitating or impeding the implementation of a COPD program in a new setting, while evaluating the implementation strategy used.

Methods

A qualitative case study was conducted using interviews, focus groups, document analysis, and site visits. Data were deductively analyzed using the Consolidated Framework for Implementation Research (CFIR) to assess the impact of each of its constructs on Best Care COPD program implementation at this site.

Results

Eleven CFIR constructs were determined to meaningfully affect implementation. Five were identified as the most influential in the implementation process. Cosmopolitanism (partnerships with other organizations), networks and communication (amongst program providers), engaging (key individuals to participate in program implementation), design quality and packaging (of the program), and reflecting and evaluating (throughout the implementation process). A peer-to-peer implementation strategy included training of registered respiratory therapists (RRT) as certified respiratory educators and the establishment of a communication network among RRTs to discuss experiences, collectively solve problems, and connect with the program lead.

Conclusions

This study provides a practical example of the various factors that facilitated the implementation of the Best Care COPD program. It also demonstrates the potential of using a peer-to-peer implementation strategy. Focusing on these factors will be useful for informing the continued spread and success of the Best Care COPD program and future implementation of other chronic care programs.
Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy
Authors: Long Junyu , Wang Dongxu , Yang Xu , Wang Anqiang , Lin Yu , Zheng Mingjun , Zhang Haohai , Sang Xinting , Wang Hanping , Hu Ke , Zhao Haitao
Published: July 2021

Background

Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy.

Methods

We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data.

Results

We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets.

Conclusions

Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.
The impact of vitamin E and/or selenium dietary supplementation on growth parameters and expression levels of the growth-related genes in broilers
Authors: Khalifa Olla A. , Al Wakeel Rasha A. , Hemeda Shabaan A. , Abdel-Daim Mohamed M. , Albadrani Ghadeer M. , El Askary Ahmad , Fadl Sabreen E. , Elgendey Fatma
Published: July 2021

Background

Broilers are continuously stressed because of the rapid growth rate and the environmental issues associated with industrialized poultry production systems, which lead to higher susceptibility for infection with pathogens. It is well known that vitamin E (Vit. E) and selenium (Se) supplementation have protective functions in such stressful conditions. This protocol was to investigate the impact of Vit. E and/or Se on the production performance, some serum biochemistry, and expression of some growth-related gene in the liver tissue of the broilers. The day-old chicks were allotted into four groups according to the supplement; Control group and groups supplemented with Vit. E and/or Se into Vit. E group (100 mg Vit. E/kg diet), Se group (0.3 mg sodium selenite/kg diet), and Vit E + Se group that supplemented with both Vit. E and Se.

Results

The data of the present experiment showed that dietary inclusion of Vit. E and/or Se significantly (P ≤ 0.05) improved the production parameters without any side effect on the general health status of the broilers, which indicated by normal serum biochemical parameters. Moreover, the treatments positively affected the expression of some genes related to growth performance including growth hormone receptor (GHR) and insulin-like growth factor 1 (IGF1) in the liver tissue of broilers.

Conclusion

Dietary supplementation of Vit. E and/or Se improved the production parameters and upregulate the growth-related genes without effect on the general health status of the broilers.
Genistein as a regulator of signaling pathways and microRNAs in different types of cancers
Authors: Javed Zeeshan , Khan Khushbukhat , Herrera-Bravo Jesús , Naeem Sajid , Iqbal Muhammad Javed , Sadia Haleema , Qadri Qamar Raza , Raza Shahid , Irshad Asma , Akbar Ali , Reiner Željko , Al-Harrasi Ahmed , Al-Rawahi Ahmed , Satmbekova Dinara , Butnariu Monica , Bagiu Iulia Cristina , Bagiu Radu Vasile , Sharifi-Rad Javad
Published: July 2021

Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.
Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis
Authors: Wu Luyao , Ding Yu , Tong Houchao , Zhuang Xi , Cai Jingsheng , Si Yan , Zhang Hao , Wang Xiaoting , Shen Meiping
Published: July 2021

Background

Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC.

Methods

The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4).

Results

Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays.

Conclusions

This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.
Therapeutic potentials of resveratrol in combination with radiotherapy and chemotherapy during glioblastoma treatment: a mechanistic review
Authors: Arabzadeh AmirAhmad , Mortezazadeh Tohid , Aryafar Tayebeh , Gharepapagh Esmaeil , Majdaeen Mehrsa , Farhood Bagher
Published: July 2021

Glioblastoma, WHO grade IV astrocytoma, is the most aggressive type of brain tumors. These cancerous cells have a rapid growth rate, tendency to penetrate vital brain structures, molecular heterogeneity, etc. and this cancer is associated with a poor prognosis and low survival rate. Due to the resistance of glioblastoma cells to conventional therapeutic modalities (such as radiation therapy and chemotherapy) as well as the adverse effects of these modalities, the researchers have attempted to discover an appropriate alternative or adjuvant treatment for glioblastoma. Resveratrol, as an herbal and natural polyphenolic compound, has anti-tumoral property and has shown to be effective in GBM treatment. Resveratrol exerts its anti-tumoral effect through various mechanisms such as regulation of cell cycle progression and cell proliferation, autophagy, oxidant system, apoptosis pathways, and so on. Resveratrol in combination with radiation therapy and chemotherapy has also been used. In the present study, we summarized the current findings on therapeutic potentials of resveratrol in glioblastoma radiotherapy and chemotherapy.
Social inequalities in the surrounding areas of food deserts and food swamps in a Brazilian metropolis
Authors: Honório Olivia Souza , Pessoa Milene Cristine , Gratão Lucia Helena Almeida , Rocha Luana Lara , de Castro Inês Rugani Ribeiro , Canella Daniela Silva , Horta Paula Martins , Mendes Larissa Loures
Published: July 2021

Background

Food deserts are neighborhoods with little or no access to healthy food, whereas food swamps are neighborhoods where unhealthy food options prevail over healthy ones. The main aims of the current study are to feature and compare the neighborhoods of food deserts and food swamps based on social inequality.

Methods

Ecological study carried out in Belo Horizonte City, Minas Gerais State, Brazil. Information about commercial food establishments derived from two different databases. It was measured by secondary governmental databases, which were virtually conferred in the present study. Census tracts were considered as analysis units and classified as food deserts and food swamps, based on the Brazilian methodology. Take into consideration the density of establishments classified as selling fresh or minimally-processed food, mixed establishments, and establishments selling ultra-processed food. The Brazilian methodology evaluates food deserts by the density of healthy establishments (establishments classified as mostly selling fresh or minimally-processed food and mixed establishments) per 10 thousand inhabitants. And the metric to evaluate food swamps considers the density of unhealthy establishments (establishments mostly selling ultra-processed food) per 10 thousand inhabitants. Information about social inequalities comprised aspects such as income, population count, number of households, number of literate individuals, race, water and energy supply, and garbage collection. The Health Vulnerability Index (HVI) was used as a synthetic social vulnerability indicator.

Results

Neighborhoods of food deserts presented worse essential service availability, lower income per capita, and smaller mean number of literate individuals. Census tracts classified as food swamps presented better socio-demographic conditions than those areas food deserts. Neighborhoods simultaneously classified as food deserts and food swamps presented lower income per capita and were more often observed in census sectors presenting medium and high HVI.

Conclusion

The food environment in Belo Horizonte was featured by the strong presence of food deserts and food swamps. However, the potential influence of these areas on food intake has changed depending on social inequalities.
Ultrasonography to detect cardiovascular damage in children with essential hypertension
Authors: Liu Wei , Hou Cui , Hou Miao , Xu Qiu-Qin , Wang Hui , Gu Pei-Pei , Sun Ling , Lv Hai-Tao , Ding Yue-Yue
Published: July 2021

Background

Essential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography.

Methods

All patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid–femoral pulse wave velocity (cfPWV), intimal–medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography.

Results

The cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E’ among three groups.

Conclusion

Children and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.
Co-developing an integrated primary care workforce planning approach at a regional level: overarching framework and guiding principles
Authors: Bourgeault Ivy Lynn , Chamberland-Rowe Caroline , Simkin Sarah
Published: July 2021

Health workforce planning provides a crucial evidence-base for decision-makers in the development and deployment of a fit-for-purpose workforce. Although less common, health workforce planning at the regional level helps to ground planning in the unique realities of local health systems. This commentary provides an overview of the process by which an integrated primary healthcare workforce planning toolkit was co-developed by university-based researchers with the Canadian Health Workforce Network and partners within a major urban regional health authority. The co-development process was guided by a conceptual framework emphasizing the key principles of sound health workforce planning: that it (1) be informed by evidence both quantitative and qualitative in nature; (2) be driven by population health needs and achieve population, worker and system outcomes; (3) recognize that deployment is geographically based and interprofessionally bound within a complex adaptive system; and (4) be embedded in a cyclical process of aligning evolving population health needs and workforce capacity.
Dosimetric comparison of MR-linac-based IMRT and conventional VMAT treatment plans for prostate cancer
Authors: Da Silva Mendes Vanessa , Nierer Lukas , Li Minglun , Corradini Stefanie , Reiner Michael , Kamp Florian , Niyazi Maximilian , Kurz Christopher , Landry Guillaume , Belka Claus
Published: July 2021

Background

The aim of this study was to evaluate and compare the performance of intensity modulated radiation therapy (IMRT) plans, planned for low-field strength magnetic resonance (MR) guided linear accelerator (linac) delivery (labelled IMRT MRL plans), and clinical conventional volumetric modulated arc therapy (VMAT) plans, for the treatment of prostate cancer (PCa). Both plans used the original planning target volume (PTV) margins. Additionally, the potential dosimetric benefits of MR-guidance were estimated, by creating IMRT MRL plans using smaller PTV margins.

Materials and methods

20 PCa patients previously treated with conventional VMAT were considered. For each patient, two different IMRT MRL plans using the low-field MR-linac treatment planning system were created: one with original (orig.) PTV margins and the other with reduced (red.) PTV margins. Dose indices related to target coverage, as well as dose-volume histogram (DVH) parameters for the target and organs at risk (OAR) were compared. Additionally, the estimated treatment delivery times and the number of monitor units (MU) of each plan were evaluated.

Results

The dose distribution in the high dose region and the target volume DVH parameters (D98%, D50%, D2% and V95%) were similar for all three types of treatment plans, with deviations below 1% in most cases. Both IMRT MRL plans (orig. and red. PTV margins) showed similar homogeneity indices (HI), however worse values for the conformity index (CI) were also found when compared to VMAT. The IMRT MRL plans showed similar OAR sparing when the orig. PTV margins were used but a significantly better sparing was feasible when red. PTV margins were applied. Higher number of MU and longer predicted treatment delivery times were seen for both IMRT MRL plans.

Conclusions

A comparable plan quality between VMAT and IMRT MRL plans was achieved, when applying the same PTV margin. However, online MR-guided adaptive radiotherapy allows for a reduction of PTV margins. With a red. PTV margin, better sparing of the surrounding tissues can be achieved, while maintaining adequate target coverage. Nonetheless, longer treatment delivery times, characteristic for the IMRT technique, have to be expected.
Clinical features and treatment efficacy for IgG4-related thyroiditis
Authors: Han Xinxin , Zhang Panpan , Li Jieqiong , Liu Zheng , Lu Hui , Luo Xuan , Pan Boju , Lian Xiaolan , Zeng Xuejun , Zhang Wen , Zeng Xiaofeng
Published: July 2021

Purpose

This study aimed to clarify the clinical features of and evaluate the treatment efficacy for IgG4-related thyroiditis.

Methods

Fourteen IgG4-related thyroiditis patients and 42 randomly matched IgG4-related disease (IgG4-RD) patients without thyroiditis in a prospective cohort at the Peking Union Medical College Hospital (PUMCH) were enrolled from 2011 to 2019. Patient demographics, clinical characteristics, laboratory parameters and treatment efficacy were analysed.

Results

The prevalence of IgG4-related thyroiditis in our cohort was 2.0%. The average patient age was 42.8 ± 14.9 years, and the male: female ratio was 1:1. Goiter (14, 100.0%), hard thyroid (14, 100.0%) and neck compression (5, 35.7%) were the most prevalent onset symptoms observed. IgG4-related thyroiditis was characterized by asymmetric diffuse thyroid enlargement on ultrasound. Thirteen (92.9%) patients had hypothyroidism, and all patients had significantly elevated circulating thyroid antibodies. Compared with patients without thyroiditis, patients with IgG4-related thyroiditis had less submandibular gland involvement and lacrimal gland involvement and lower serum IgG4 and T-IgE levels (P = 0.019, P = 0.022, P = 0.004, and P = 0.006, respectively) and more single-organ involvement (P = 0.011). After treatment, the symptoms were relieved, while the size of the thyroid gland did not change significantly, and levothyroxine as a supplemental therapy was still needed.

Conclusions

IgG4-related thyroiditis is a distinct subtype of IgG4-RD characterized by positive circulating thyroid antibodies and a high rate of hypothyroidism. Although compression symptoms could be relieved with treatment, the thyroid size did not change significantly, and the damage to thyroid function was often irreversible.
Circulating extracellular vesicles from individuals at high-risk of lung cancer induce pro-tumorigenic conversion of stromal cells through transfer of miR-126 and miR-320
Authors: Pontis Francesca , Roz Luca , Mensah Mavis , Segale Miriam , Moro Massimo , Bertolini Giulia , Petraroia Ilaria , Centonze Giovanni , Ferretti Anna Maria , Suatoni Paola , Pastorino Ugo , Fortunato Orazio , Sozzi Gabriella
Published: July 2021

Background

Extracellular vesicles (EVs) containing specific subsets of functional biomolecules are released by all cell types and analysis of circulating EVs can provide diagnostic and prognostic information. To date, little is known regarding the role of EVs both as biomarkers and potential key players in human lung cancer.

Methods

Plasma EVs were isolated from 40 cancer-free heavy-smokers classified according to a validated 24-microRNA signature classifier (MSC) at high (MSCpos-EVs) or low (MSCneg-EVs) risk to develop lung cancer. EVs origin and functional properties were investigated using in vitro 3D cultures and in vivo models. The prognostic value of miRNAs inside EVs was assessed in training and in validation cohorts of 54 and 48 lung cancer patients, respectively.

Results

Different membrane composition, biological cargo and pro-tumorigenic activity were observed in MSCpos vs MSCneg-EVs. Mechanistically, in vitro and in vivo results showed that miR-126 and miR-320 from MSCpos-EVs increased pro-angiogenic phenotype of endothelial cells and M2 polarization of macrophage, respectively. MSCpos-EVs prompted 3D proliferation of non-tumorigenic epithelial cells through c-Myc transfer. Moreover, hypoxia was shown to stimulate the secretion of EVs containing c-Myc from fibroblasts, miR-126-EVs from endothelial cells and miR-320-EVs from granulocytes. Lung cancer patients with higher levels of mir-320 into EVs displayed a significantly shorter overall survival in training [HR2.96] and validation sets [HR2.68].

Conclusion

Overall our data provide a new perspective on the pro-tumorigenic role of circulating EVs in high risk smokers and highlight the significance of miR-320-EVs as a new prognostic biomarker in lung cancer patients.
Effects of variable frequencies of kinesthesia, balance and agility exercise program in adults with knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Adhama Aysha I. , Akindele Mukadas O. , Ibrahim Aminu A.
Published: July 2021

Background

Knee osteoarthritis (OA) is a common painful and disabling condition that affects older individuals. Proprioceptive training programs in the form of kinesthesia, balance and agility (KBA) exercises have been reported to be beneficial for individuals with knee OA. However, the most optimal training dosage of KBA exercises is still unclear. The aim of this study is to determine the effects of different frequencies of KBA training (i.e., twice-weekly or thrice-weekly) in adults with knee OA.

Methods

A single (assessor) blind, three-arm parallel, multi-center randomized controlled trial will be conducted. One hundred twenty adults with knee OA will be recruited from four tertiary hospitals in Northwestern Nigeria and randomly assigned into one of three intervention groups; twice-weekly KBA (n = 40), thrice-weekly KBA (n = 40), and conventional physiotherapy (n = 40) in the ratio of 1:1:1. Participants in the conventional physiotherapy group will receive two sessions of brief patient education, and sixteen sessions of ultrasound therapy, and stretching and strengthening exercises for 8 weeks. Participants in the two different KBA groups will receive KBA training according to the designed sessions for 8 weeks in addition to the conventional physiotherapy program. All groups will be assessed pre-intervention, immediately post-intervention and at 3 months, 4 months, and 6 months post-randomization. The primary outcome will be physical function (Ibadan Knee and Hip Osteoarthritis Outcome Measure) whereas the secondary outcomes will be pain intensity (Visual Analogue Scale for pain), knee stability (Knee Outcome Survey-Activities of Daily Living Scale), proprioception (electronic goniometer), and quality of life (Osteoarthritis Knee and Hip Quality of Life Questionnaire).

Discussion

The findings of this study may provide evidence on the effectiveness of KBA exercise training and the ideal number of sessions needed to achieve the highest effectiveness in adults with knee OA.

Trial registration

Pan African Clinical Trials Registry (PACTR201810713260138). Registered on 28 November 2017.
Preservation of the ovarian reserve and hemostasis during laparoscopic ovarian cystectomy by a hemostatic agent versus suturing for patients with ovarian endometriosis: study protocol for randomized controlled, non-inferiority trial (PRAHA-2 trial)
Authors: Lim Hyunji , Park Soo Jin , Paik Haerin , Mun Jaehee , Lee Eun Ji , Lee Seungmee , Lim Whasun , Song Gwonhwa , Shim Seung-Hyuk , Lee Chae Hyeong , Yim Ga Won , Kim Hee Seung ,   PRAHA Study Group
Published: July 2021

Background

Endometriosis (EMS) can be implanted everywhere, especially in pelvic organs. EMS can be asymptomatic, but it can result in pelvic pain and infertility by inducing local inflammation and pelvic adhesion. The prevalence of EMS is about 10% in reproductive-age women and higher in women with pelvic pain or infertility. For young patients with ovarian EMS, laparoscopic ovarian cystectomy is effective in relieving pelvic pain and preventing local recurrence. However, there is a concern that the ovarian reserve would decrease after the operation because of the removal of a part of the normal ovarian tissue and thermal damage during hemostasis, which depends on the types of hemostasis such as bipolar electrocoagulation, suturing, and the use of a hemostatic agent. In this study, we aim to evaluate the protective effect for the ovarian reserve and hemostasis between a hemostatic agent and suturing during laparoscopic ovarian cystectomy for patients with ovarian EMS.

Methods

This study is a randomized controlled, non-inferiority trial, where a total of 90 patients with ovarian EMS will be randomly assigned to the experimental (hemostatic agent) and control (suturing) groups. In the control group, a barbed suture will be applied for hemostasis, whereas a hemostatic agent will be applied in the experimental group. If two methods are insufficient, bipolar electrocoagulation will be applied for complete hemostasis. As the primary endpoint, the reduction rate of serum anti- Müllerian hormone (AMH) levels reflecting the ovarian reserve will be compared between the two groups 12 weeks after surgery. As secondary endpoints, we will compare the reduction rate of AMH level 48 weeks after surgery, the time required to complete hemostasis, the success rate of hemostasis within 10 min, and adverse events associated with operation.

Discussion

We expect that the protective effect for the ovarian reserve and hemostasis may be comparable between the two methods, suggesting that a hemostatic agent may be preferred considering that it is easy to use during laparoscopic ovarian cystectomy.

Trial registration

ClinicalTrials.govNCT04643106. Registered on 22 November 2020
Community-based intervention for prevention and management of chronic obstructive pulmonary disease in Nepal (COBIN-P trial): study protocol for a cluster-randomized controlled trial
Authors: Adhikari Tara Ballav , Neupane Dinesh , Karki Arjun , Drews Arne , Cooper Brendan , Högman Marieann , Sigsgaard Torben , Kallestrup Per
Published: July 2021

Background

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide and the commonest of non-communicable diseases (NCDs) in Nepal. Risk factors like indoor and outdoor air pollution, a high prevalence of smoking, and the lack of awareness of COPD make it a serious public health concern. However, no attempt has been made in Nepal to estimate its burden and address the disease at the community level.

Method

This study aims to evaluate the effect of a community-based health educational intervention administered by Female Community Health Volunteers (FCHVs) on the prevention and management of COPD. An open-label, two-group, community-based, cluster-randomized controlled trial will be implemented in the semi-urban area of Pokhara Metropolitan city (former Lekhnath Municipality) located in the Kaski district of Nepal. The estimated sample size of the intervention will be 1143. The unit of randomization is the ward (administrative unit) of the study area. The follow-up survey will be conducted immediately after 12 months of FCHVs-led interventions. The difference in the rate of decline of forced expiratory volume in 1 s (FEV1) and FEV1/FVC (forced vital capacity) ratio are the primary outcomes and the change in the proportion of modifiable risk factors of COPD, health-related quality of life scores, and change in knowledge of COPD will be secondary outcomes.

Discussion

This study will estimate the burden of COPD, the magnitude of risk factors and generate evidence to mobilize community health workers for COPD prevention and management at the community level in Nepal.

Trial registration

ClinicalTrials.gov NCT03797768. Registered on January 9, 2019.
Phlebotomine sand fly survey in the Republic of Moldova: species composition, distribution and host preferences
Authors: Șuleșco Tatiana , Erisoz Kasap Ozge , Halada Petr , Oğuz Gizem , Rusnac Dimian , Gresova Marketa , Alten Bulent , Volf Petr , Dvorak Vit
Published: July 2021

Background

Phlebotomine sand flies (Diptera: Psychodiae) in the Republic of Moldova have been understudied for decades. Our study provides a first update on their occurrence, species composition and bloodmeal sources after 50 years.

Methods

During 5 seasons (2013–2017), 58 localities from 20 regions were surveyed for presence of sand flies using CDC light traps and manual aspirators. Species identification was done by a combination of morphological and molecular approaches (DNA barcoding, MALDI-TOF MS protein profiling). In engorged females, host blood was identified by three molecular techniques (RFLP, cytb sequencing and MALDI-TOF peptide mass mapping). Population structure of most abundant species was studied by cox1 haplotyping; phylogenetic analyses of ITS2 and cox1 genetic markers were used to resolve relationships of other detected species.

Results

In total, 793 sand flies were collected at 30 (51.7%) localities from 12 regions of Moldova. Three species were identified by an integrative morphological and molecular approach: Phlebotomus papatasi, P. perfiliewi and Phlebotomus sp. (Adlerius), the first being the most abundant and widespread, markedly anthropophilic based on bloodmeal analyses, occurring also indoors and showing low population structure with only five haplotypes of cox1 detected. Distinct morphological and molecular characters of Phlebotomus sp. (Adlerius) specimens suggest the presence of a yet undescribed species.

Conclusions

Our study revealed the presence of stable sand fly populations of three species in Moldova that represent a biting nuisance as well as a potential threat of pathogen transmission and shall be further studied.

Graphical abstract
Altered circulating CCR6+and CXCR3+ T cell subsets are associated with poor renal prognosis in MPO-ANCA-associated vasculitis
Authors: Liao Zhonghua , Tang Jiale , Luo Liying , Deng Shuanglinzi , Luo Lisa , Wang Fangyuan , Yuan Xiangning , Hu Xinyue , Feng Juntao , Li Xiaozhao
Published: July 2021

Background

Effector memory T cells are pivotal effectors of adaptive immunity with enhanced migration characteristics and are involved in the pathogenesis of ANCA-associated vasculitis (AAV). The diversity of effector memory T cells in chemokine receptor expression has been well studied in proteinase 3 (PR3)-AAV. However, few studies have been conducted in myeloperoxidase (MPO)-AAV. Here, we characterized chemokine receptor expression on effector memory T cells from patients with active MPO-AAV.

Methods

Clinical data from newly diagnosed MPO-AAV patients and healthy subjects were collected and analyzed. Human peripheral blood mononuclear cells (PBMCs) isolated from patients with active MPO-AAV were analyzed by flow cytometry. The production of effector memory T cell-related chemokines in serum was assessed by ELISA.

Results

We observed decreased percentages of CD4+and CD8+T cells in the peripheral blood, accompanied by a significant decrease in CCR6-expressing T cells but an increase in CXCR3+T cells, in active MPO-AAV. Furthermore, the decrease in CCR6 and increase in CXCR3 expression were mainly limited to effector memory T cells. Consistent with this finding, the serum level of CCL20 was increased. In addition, a decreasing trend in the TEM17 cell frequency, with concomitant increases in the frequencies of CD4+TEM1 and CD4+TEM17.1 cells, was observed when T cell functional subsets were defined by chemokine receptor expression. Moreover, the proportions of peripheral CD8+T cells and CD4+TEMsubsets were correlated with renal prognosis and inflammatory markers.

Conclusions

Our data indicate that dysregulated chemokine receptor expression on CD4+and CD8+effector memory T cells and aberrant distribution of functional CD4+T cell subsets in patients with active MPO-AAV have critical roles related to kidney survival.
Clinical characteristics, imaging phenotypes and events free survival in Takayasu arteritis patients with hypertension
Authors: Ying Sun , Sifan Wu , Yujiao Wang , Rongyi Chen , Qingrong Huang , Lili Ma , Huiyong Chen , Lindi Jiang
Published: July 2021

Background

Hypertension occurred in 30–80% of Takayasu arteritis (TAK) patients around the world and the occurrence of hypertension might worsen the disease prognosis. This study aimed to investigate the clinical characteristics and imaging phenotypes, as well as their associations with events free survival (EFS) in Chinese TAK patients with hypertension.

Methods

This current research was based on a prospectively ongoing observational cohort-the East China Takayasu Arteritis (ECTA) cohort, centered in Zhongshan Hospital, Fudan University. Totally, 204 TAK patients with hypertension were enrolled between January 2013 and December 2019. Clinical characteristics and imaging phenotypes of each case were evaluated and their associations with the EFS by the end of August 30, 2020, were analyzed.

Results

Severe hypertension accounted for 46.1% of the entire population. Three specific imaging phenotypes were identified: Cluster 1: involvement of the abdominal aorta and/or renal artery (27.5%); Cluster 2: involvement of the ascending aorta, thoracic aorta, the aortic arch, and/or its branches (18.6%); and Cluster 3: combined involvement of Cluster 1 and 2 (53.9%). Clinical characteristics, especially hypertensive severity, differed greatly among the three imaging clusters. In all, 187 patients were followed up for a median of 46 (9–102) months; 72 events were observed in 60 patients (1–3 per person). The overall blood pressure control rate was 50.8%, and the EFS was 67.9% by the end of the follow-up. Multivariate Cox regression indicated that controlled blood pressure (HR = 2.13, 95% CI 1.32–3.74), Cluster 1 (HR = 0.69, 95% CI 0.48–0.92) and Cluster 3 (HR = 0.72, 95% CI 0.43–0.94) imaging phenotype was associated with the EFS. Kaplan–Meier curves showed that patients with controlled blood pressure showed better EFS (p = 0.043). Furthermore, using cases with Cluster 1 imaging phenotype and controlled blood pressure as reference, better EFS was observed in patients with Cluster 2 phenotype and controlled blood pressure (HR = 2.21, 95%CI 1.47–4.32), while the case with Cluster 1 phenotype plus uncontrolled blood pressure (HR = 0.64, 95%CI 0.52–0.89) and those with Cluster 3 phenotype and uncontrolled blood pressure (HR = 0.83, 95%CI 0.76–0.92) suffered worse EFS.

Conclusion

Blood pressure control status and imaging phenotypes showed significant effects on the EFS for TAK patients with hypertension.
Modeling organizational intelligence, learning, forgetting and agility using structural equation model approaches in Shiraz University of Medical Sciences Hospitals
Authors: Kavosi Zahra , Delavari Sajad , Kiani Mohammad Mehdi , Bastani Peivand , Vali Mohebat , Salehi Marzieh
Published: July 2021

Objectives

Strengthening the organizational agility of the hospital can lead to decreased production costs and increased market share, better serving to patients' needs, introduction of new services and increased competitiveness; therefore, this study aimed to investigate the agility of Shiraz public teaching hospitals.

Results

The results showed that organizational intelligence had a positive and significant effect on organizational agility with a path coefficient of 0.172. Organizational forgetting and organizational learning also played a mediating role between organizational intelligence and organizational agility. This means that organizational intelligence had positive effect on organizational forgetting with path coefficient of 0.482, organizational forgetting on organizational learning with path coefficient of 0.40 and subsequently organizational learning on organizational agility with path factor of 0.07. Organizational forgetting also played a mediating role between organizational intelligence and organizational learning.
Retrospective analysis of the clinical presentation and imaging of eight primary benign mediastinal schwannomas
Authors: Sandoval-Macias Ramiro , Ortiz-Sanchez Irving Daniel , Remirez-Castellanos Ana Lilia , Mora-Hernandez Luis , Cordova-Uscanga Candelaria , Mantilla-Morales Alejandra , Galindo-Garcia Tania Alejandra , Gamboa-Dominguez Armando , Candanedo-Gonzalez Fernando
Published: July 2021

Objective

Mediastinal schwannomas are sometimes confused with other neoplasms during initial radiological studies, especially when there is a history of cancer in another area. In these cases, a more accurate analysis using computed tomography (CT) or even magnetic resonance (MRI) is required. Our study aimed to perform a retrospective analysis of the clinical and imaging features for a series of patients with mediastinal schwannomas that were confirmed by histology and immunohistochemistry.

Results

We found eight patients, five men and three women, with an average age of 51 years for this study. The main signs and symptoms at diagnosis were chest pain, dyspnea, cough, and dysphagia. CT showed that the tumor was located in the posterior compartment of the chest in 7/8 cases. Tumors > 10 cm were more heterogeneous and showed cystic changes. All patients underwent posterolateral thoracotomy, and radiological follow-up showed no evidence of recurrence. Histological analysis was considered the gold standard to confirm diagnosis, along with at least one neurogenic IHC marker. In conclusion, mediastinal schwannomas are benign encapsulated tumors. According to CT, schwannomas > 10 cm show cystic degeneration more frequently. Posterolateral thoracotomy allows complete resection and is considered the surgical approach of choice.