bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life of patients with soft tissue sarcoma treated with doxorubicin in the ANNOUNCE phase III clinical trial
Authors: Van Tine Brian A , Krarup-Hansen Anders , Hess Lisa M , Abdul Razak Albiruni R , Soldatenkova Victoria , Wright Jennifer , Park Se Hoon
Published: May 2022

Background: Patient-reported outcomes (PROs), including health-related quality of life, are recommended to be routinely collected in clinical trials, but data are limited from trials of sarcoma patients. In this analysis, pooled PRO data are reported from patients with advanced or metastatic soft tissue sarcoma (STS) enrolled to the ANNOUNCE phase III trial of doxorubicin-based therapy. Methods: ANNOUNCE was a phase III trial that randomized 509 patients with STS to receive up to eight cycles of doxorubicin with olaratumab or placebo, followed by single-agent olaratumab or placebo. Dexrazoxane was allowed at any cycle of treatment. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30, which is scored 0–100), and Brief Pain Inventory Short Form Modified (mBPI-sf, scored from 0–10) at each treatment cycle. A descriptive analysis of the longitudinal data was conducted overall and by cumulative dose of doxorubicin received to inform the clinical care of patients with STS. Worsening on the QLQ-C30 was defined as a change of 10 points or more at any post-baseline assessment. Worsening on the mPBI-sf was defined as an increase of ≥2 points from baseline. Results: The majority of participants completed the baseline and at least one subsequent PRO assessment within the trial ( n = 460, 90.4% EORTC QLQ-C30; n = 454, 89.2%, mBPI-sf). Patients with STS enrolled to the ANNOUNCE trial had clinically meaningful problems with physical function and pain before initiating doxorubicin. Overall, those with fewer symptoms or better function at baseline received higher cumulative doxorubicin dose throughout the study. At baseline, mean QLQ-C30 fatigue was 29.9 with a median time to first worsening of 0.9 months, and mean nausea/vomiting was 6.5 with 1.4 months until worsening; mean physical function was 78.3 with median time to worsening of 2.1 months and mean health status was 66.8 with median time to first worsening of 1.6 months. Median time to worsening of pain was 7.9 months. Conclusion: Patients with advanced or metastatic sarcoma reported a relatively rapid decline in PROs during doxorubicin-based treatment, with patients with poorer symptoms at baseline (specifically fatigue), subsequently receiving less doxorubicin therapy. The availability of detailed summary data from the patient perspective during doxorubicin-based treatment may inform future care of these patients and can provide a resource for the development of PRO endpoints in future trials.
Granulomatosis With Polyangiitis Presenting as Occlusive Retinal Vasculitis
Authors: D’Aquila Madeline L. , John Vishak J.
Published: May 2022

Purpose:

We discuss an unusual case of granulomatosis with polyangiitis (GPA) presenting as anterior uveitis with occlusive retinal vasculitis.

Methods:

A case report is presented.

Results:

A 60-year-old woman with a history of autoimmune disease presented to the retina clinic with red eyes and blurry vision in both eyes. An examination showed anterior uveitis with retinal vasculitis, and topical steroids were started in both eyes. One month later, the patient’s vision worsened and an optical coherence tomography scan showed new central cystoid macular edema in the left eye. An antivascular endothelial growth factor injection was given. The next day, her vision was “black” in the left eye and a fundus examination showed global ischemia. A comprehensive uveitis workup was positive for cytoplasmic-staining antineutrophilic cytoplasmic antibody. A diagnosis of GPA was confirmed with a renal biopsy.

Conclusions:

Physician awareness of ocular GPA presentation is vital, and GPA management is most successful with a multidisciplinary team.
Caregiver-specific factors and orphanage-context factors contributing to maltreatment of children in institutional care: A multi-level analysis of 24 orphanages in Tanzania
Authors: Mkinga Getrude , Kirika Anette , Nkuba Mabula , Mgode Simeon , Huth Mira , Hecker Tobias
Published: May 2022

Background: High rates of maltreatment and low caregiving quality in institutional care settings have been identified in various low-and middle-income countries. Many studies have focused on children living in institutions. Objective: This study investigates the prevalence of maltreatment, caregiver-specific, orphanage-context factors, and their relation to maltreatment of orphans from the caregivers’ perspective. Participants and setting: In this cross-sectional study, 227 caregivers (67% female) with a mean age of 36.84 years ( SD age = 12.89) of 24 childcare centres in Dar es Salaam, Tanzania participated. Methods: The primary outcome was the maltreatment of children assessed through structured interviews of caregivers. Further information on individual (like work-related stress) and structural variables (working conditions) was gathered. Results: Caregivers’ work under extreme and exhausting conditions, with very high caregiver-child ratios, low salaries, and almost no possibility to recover. Results also showed significant differences in the maltreatment level and structural and individual factors (e.g., payment and days of entitlement) between the orphanages. Caregiver’s positive attitudes towards violence ( ƒ2attitudes = 0.19) and difficulties in the relationship with children ( ƒ2relationship = 0.05) significantly predicted maltreatment with moderate and small effects. Conclusions: The overall poor working conditions highlight the urgent need to reduce the caregivers’ burden. In addition to this, addressing caregivers’ positive attitudes and improving their interaction competencies with children may be a starting point to prevent maltreatment of children. Further investigation of structural factors contributing to maltreatment is essential to develop recommendations for the improvement and re-organization of childcare institutions.
Promoting Gender Inclusivity in General Music (part 2): Considerations for Using Technology
Authors: Culp Mara E. , Robison Tiger
Published: May 2022

This article is the second in a series intended to assist general music teachers in creating gender-inclusive music environments. Technology can be used in general music classrooms to support learning and to extend musical creativity. Previous authors have shared ideas that can help general music teachers use technology in ways that promote more gender-inclusive environments by helping all learners effectively use technology. The purpose of this article is to help general music teachers identify and incorporate strategies for using technology in their classrooms that support students of all genders. Specific strategies, such as purposeful role models, student groupings, and family support, as well as resources are included. Through thoughtful and purposeful integration informed by relevant literature and research, technology can be used to develop children’s musicianship.
Assessing the Standards: An Exploration of the Respond Model Cornerstone Assessment
Authors: Hatch Emily
Published: May 2022

Along with standards describing what music students should be able to do, the National Core Arts Standards developed Model Cornerstone Assessments suggesting how teachers can measure student learning for each artistic process. This article explores the Respond Model Cornerstone Assessment. This column explains the Model Cornerstone Assessment for the Respond process; discusses what students need to know to succeed on the assessment; and explores ways for teachers to modify the assessment and use the data to refine their teaching.
The Atrophy of the Vagus Nerve Correlated With Gastrointestinal Non-Motor Symptoms Scores, in Parkinson’s Disease: A Sonography Research Study
Authors: Özçağlayan Ömer , Altunan Bengü , Kurtoğlu Özçağlayan Tuğba İlkem , Ünal Aysun
Published: May 2022

Objective:

To investigate the vagus nerve (VN) dimensional changes with Parkinson’s disease (PD), compared with healthy subjects. Additionally, it is important to investigate whether there is any relationships between these changes and patient’s motor and non-motor symptoms (NMS) of PD.

Materials and Methods:

A cohort of 43 patients with PD formed a group that was compared with 44 patients without PD, denoted as the healthy subject (HS) group. The diameter and areas of VN of study groups were measured using ultrasonography (US). The study groups were further divided into <65 and ≥65 subgroups, to evaluate the possible effect of age on the VN and evaluated relationships of VN dimensions, between subgroups. In the PD group, a correlational analysis was conducted between the diameter and area of the VN and the motor and NMS scores.

Results:

There was statistically significant difference in right ( P = .002) and left VN diameters ( P = .007) and in right ( P = .001) and left VN areas ( P = .007), between study groups. There was no significant difference in right and left VN diameters and the right and left VN areas, between subgroups. There was moderately negative correlation between gastrointestinal NMS scores and right VN area ( r = −0.499, P = .002), left VN area ( r = −0.499, P = .002), right VN diameter ( r = −0.378, P = .023), left VN diameter ( r = −0.385, P = .021), respectively.

Conclusion:

The US demonstrated that VN dimensions may possibly reduce in those patients affected by PD. In this cohort, it appears that an increase in gastrointestinal NMS scores may be explained by atrophy of the VN.
Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms
Authors: Sperling Adam S. , Guerra Veronica A. , Kennedy James A. , Yan Yuanqing , Hsu Joanne I. , Wang Feng , Nguyen Andrew T. , Miller Peter G. , McConkey Marie E. , Quevedo Barrios Vanessa A. , Furudate Ken , Zhang Linda , Kanagal-Shamanna Rashmi , Zhang Jianhua , Little Latasha , Gumbs Curtis , Daver Naval , DiNardo Courtney D. , Kadia Tapan , Ravandi Farhad , Kantarjian Hagop , Garcia-Manero Guillermo , Futreal P. Andrew , Ebert Benjamin L. , Takahashi Koichi
Published: May 2022

There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background of clonal hematopoiesis (CH) under the positive selective pressure of chemo- and radiation therapies. Uncovering the exposure relationships that provide selective advantage to specific CH mutations is critical to understanding the pathogenesis and etiology of t-MNs. In a systematic analysis of 416 patients with t-MN and detailed prior exposure history, we found that TP53 mutations were significantly associated with prior treatment with thalidomide analogs, specifically lenalidomide. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem and progenitor cells (HSPCs) in vitro and in vivo, the effect of which was specific to Trp53-mutant HSPCs and was not observed in HSPCs with other CH mutations. Because of the differences in CK1α degradation, pomalidomide treatment did not provide an equivalent level of selective advantage to Trp53-mutant HSPCs, providing a biological rationale for its use in patients at high risk for t-MN. These findings highlight the role of lenalidomide treatment in promoting TP53-mutated t-MNs and offer a potential alternative strategy to mitigate the risk of t-MN development.
Lung cancer in patients with fibrosing interstitial lung diseases: an overview of current knowledge and challenges
Authors: Kewalramani Namrata , Machahua Carlos , Poletti Venerino , Cadranel Jacques , Wells Athol U. , Funke-Chambour Manuela
Published: May 2022

Patients with progressive fibrosing interstitial lung diseases (fILD) have increased morbidity and mortality. Lung fibrosis can be associated with lung cancer. The pathogenesis of both diseases shows similarities, although not all mechanisms are understood. The combination of the diseases is challenging, due to the amplified risk of mortality, and also because lung cancer treatment carries additional risks in patients with underlying lung fibrosis. Acute exacerbations in fILD patients are linked to increased mortality, and the risk of acute exacerbations is increased after lung cancer treatment with surgery, chemotherapy or radiotherapy. Careful selection of treatment modalities is crucial to improve survival while maintaining acceptable quality of life in patients with combined lung cancer and fILD. This overview of epidemiology, pathogenesis, treatment and a possible role for antifibrotic drugs in patients with lung cancer and fILD is the summary of a session presented during the virtual European Respiratory Society Congress in 2021. The review summarises current knowledge and identifies areas of uncertainty. Most current data relate to patients with combined idiopathic pulmonary fibrosis and lung cancer. There is a pressing need for additional prospective studies, required for the formulation of a consensus statement or guideline on the optimal care of patients with lung cancer and fILD.
People living with moderate-to-severe COPD prefer improvement of daily symptoms over the improvement of exacerbations: a multicountry patient preference study
Authors: Cook Nigel S. , Criner Gerard J. , Burgel Pierre-Régis , Mycock Katie , Gardner Tom , Mellor Phil , Hallworth Pam , Sully Kate , Tatlock Sophi , Klein Beyza , Jones Byron , Le Rouzic Olivier , Adams Kip , Phillips Kirsten , McKevitt Mike , Toyama Kazuko , Gutzwiller Florian S.
Published: May 2022

Introduction

This patient preference study sought to quantify the preferences of people living with COPD regarding symptom improvement in the UK, USA, France, Australia and Japan.

Methods

The inclusion criteria were people living with COPD aged 40 years or older who experienced ≥1 exacerbation in the previous year with daily symptoms of cough and excess mucus production. The study design included: 1) development of an attributes and levels grid through qualitative patient interviews; and 2) implementation of the main online quantitative survey, which included a discrete choice experiment (DCE) to allow assessment of attributes and levels using hypothetical health state profiles. Preference weights (utilities) were derived from the DCE using hierarchical Bayesian analysis. A preference simulator was developed that enabled different health state scenarios to be evaluated based on the predicted patient preferences.

Results

1050 people living with moderate-to-severe COPD completed the survey. All attributes were considered important when patients determined their preferences in the DCE. In a health state preference simulation, two hypothetical health states (comprising attribute levels) with qualitatively equivalent improvements in A) cough and mucus and B) shortness of breath (SOB) resulted in a clear preference for cough and mucus improved profile. When comparing two profiles with C) daily symptoms improved and D) exacerbations improved, there was a clear preference for the daily symptoms improved profile.

Conclusions

People living with moderate-to-severe COPD prefer to reduce cough and mucus production together over improvement of SOB and would prefer to reduce combined daily symptoms over an improvement in exacerbations.
Identification of immune infiltration-related genes as prognostic indicators for hepatocellular carcinoma
Authors: Dai Kunfu , Liu Chao , Guan Ge , Cai Jinzhen , Wu Liqun
Published: May 2022

Hepatocellular carcinoma (HCC) has a high degree of malignancy and a poor prognosis. Immune infiltration-related genes have shown good predictive value in the prognosis of many solid tumours. In this study, we established and verified prognostic biomarkers consisting of immune infiltration-related genes in HCC. Gene expression data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Differential gene expression analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression algorithm were used to screen prognostic immune infiltration-related genes and to construct a risk scoring model. Kaplan-Meier (KM) survival plots and receiver operating characteristic (ROC) curve analysis were used to evaluate the prognostic performance of the risk scoring model in the TCGA-HCC cohort. In addition, a nomogram model with a risk score was established, and its predictive performance was verified by ROC analysis and calibration plot analysis in the TCGA-HCC cohort. Gene set enrichment analysis (GSEA) identified pathways and biological processes that may be enriched in the high-risk group. Finally, immune infiltration analysis was used to explore the characteristics of the tumour microenvironment related to the risk score. We identified 17 immune infiltration-related genes with prognostic value and constructed a risk scoring model. ROC analysis showed that the risk scoring model can accurately predict the 1-year, 3-year, and 5-year overall survival (OS) of HCC patients in the TCGA-HCC cohort. KM analysis showed that the OS of the high-risk group was significantly lower than that of the low-risk group (P < 0.001). The nomogram model effectively predicted the OS of HCC patients in the TCGA-HCC cohort. GSEA indicated that the immune infiltration-related genes may be involved in biological processes such as amino acid and lipid metabolism, matrisome and small molecule transportation, immune system regulation, and hepatitis virus infection. Immune infiltration analysis showed that the level of immune cell infiltration in the high-risk group was low, and the risk score was negatively correlated with infiltrating immune cells. Our prognostic model based on immune infiltration-related genes in HCC could help the prognostic assessment of HCC patients and provide potential targets for HCC inhibition.
Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer
Authors: Glass Evan B. , Hoover Alyssa A. , Bullock Kennady K. , Madden Matthew Z. , Reinfeld Bradley I. , Harris Whitney , Parker Dominique , Hufnagel Demetra H. , Crispens Marta A. , Khabele Dineo , Rathmell W. Kimryn , Rathmell Jeffrey C. , Wilson Andrew J. , Giorgio Todd D. , Yull Fiona E.
Published: May 2022

Background

Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer.

Methods

We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models.

Results

Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model.

Conclusions

In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies.
Living with presbyopia: experiences from a virtual roundtable dialogue among impacted individuals and healthcare professionals
Authors: Brujic Mile , Kruger Paola , Todd Jeff , Barnes Elizabeth , Wuttke Mark , Perna Flavia , Aliò Jorge
Published: May 2022

Background

Presbyopia is a common progressive vision disorder characterised by an inability to focus on near objects. The emergence of newer treatment options in addition to spectacles or contact lenses highlights the importance of assessing patient/user preferences.

Methods

People with presbyopia and healthcare professionals (HCPs) took part in a moderated, structured discussion of specific questions on a virtual advisory-board platform. The objective was to better understand unmet needs and the experience of living with the condition. Closed and open questions were included.

Results

Nine individuals (age 40 to 70 years) with presbyopia participated, from Australia, China, France, Italy, Ireland, Japan and the US. One ophthalmologist and one optometrist represented the perspective of HCPs. Over two weeks, 621 posts were entered on the platform. There was widespread agreement that the often stated association between age and presbyopia was unfortunate. Some participants had developed presbyopia at 30–45 years of age. What is more, the association with age was seen as implying a natural process, reducing the incentive to treat. Instead there was a call for an action-oriented view of presbyopia as a condition which may be effectively treated in the future. All participants experienced dealing with presbyopia as burdensome, affecting quality of life to varying degrees. When considering new treatments, convenience was the most important factor. The option to administer drops when needed was considered favourable, but short-acting treatments may not reduce inconvenience compared with spectacles. Participants viewed a therapy that targets the underlying cause of the condition favourably compared with symptomatic treatment. Side effects would severely reduce the appeal of drops. For clinical trials in presbyopia, patient-reported outcomes should be mandatory and need adequately to capture quality of life. Studies in presbyopia must be designed to minimise the inconvenience to participants in order to counter the risk of high drop-out rates.

Conclusions

The interactive format provided insights into living with presbyopia, particularly the negative impact on quality of life, subjects’ openness to new therapies, and the need to move away from considering the condition an unavoidable and intractable consequence of ageing.
Unconditional cash transfers and maternal substance use: findings from a randomized control trial of low-income mothers with infants in the U.S.
Authors: Yoo Paul Y. , Duncan Greg J. , Magnuson Katherine , Fox Nathan A. , Yoshikawa Hirokazu , Halpern-Meekin Sarah , Noble Kimberly G.
Published: May 2022

Background

Policy debates over anti-poverty programs are often marked by pernicious stereotypes suggesting that direct cash transfers to people residing in poverty encourage health-risking behaviors such as smoking, drinking, and other substance use. Causal evidence on this issue is limited in the U.S. Given the prominent role of child allowances and other forms of cash assistance in the 2021 American Rescue Plan and proposed Build Back Better legislation, evidence on the extent to which a monthly unconditional cash gift changes substance use patterns among low-income mothers with infants warrants attention, particularly in the context of economic supports that can help improve early environments of children.

Method

We employ a multi-site, parallel-group, randomized control trial in which 1,000 low-income mothers in the U.S. with newborns were recruited from hospitals shortly after the infant’s birth and randomly assigned to receive either a substantial ($333) or a nominal ($20) monthly cash gift during the early years of the infant’s life. We estimate the effect of the unconditional cash transfer on self-report measures of maternal substance use (i.e., alcohol, cigarette, or opioid use) and household expenditures on alcohol and cigarettes after one year of cash gifts.

Results

The cash gift difference of $313 per month had small and statistically nonsignificant impacts on group differences in maternal reports of substance use and household expenditures on alcohol or cigarettes. Effect sizes ranged between − 0.067 standard deviations and + 0.072 standard deviations. The estimated share of the $313 group difference spent on alcohol and tobacco was less than 1%.

Conclusions

Our randomized control trial of monthly cash gifts to mothers with newborn infants finds that a cash gift difference of $313 per month did not significantly change maternal use of alcohol, cigarettes, or opioids or household expenditures on alcohol or cigarettes. Although the structure of our cash gifts differs somewhat from that of a government-provided child allowance, our null effect findings suggest that unconditional cash transfers aimed at families living in poverty are unlikely to induce large changes in substance use and expenditures by recipients.

Trial Registration

Registered on Clinical Trials.gov NCT03593356 in July of 2018.
Pregnant adolescents’ lived experiences and coping strategies in peri-urban district in Southern Ghana
Authors: Kotoh Agnes M. , Sena Amekudzie Bernice , Opoku-Mensah Kwabena , Baku Elizabeth Aku , Glozah Franklin N.
Published: May 2022

Background

Adolescence, a transition period from childhood to adulthood forms the foundation of health in later life. The adolescence period which should have been characterised by good health is often marred with life-threatening and irreparable consequences of public health concern. Teen pregnancy is problematic because it could jeopardise adolescents’ safe transition to adulthood which does not only affect adolescents, but also their families, babies and society. There is ample evidence about the determinants and effects of teen pregnancy, but it is fragmented and incomplete, especially in Sub-Sahara Africa. This study presents pregnant adolescents’ voices to explain significant gaps in understanding their lived experiences and coping strategies.

Methods

This narrative inquiry, involved in-depth interviews with 16 pregnant adolescents, who were recruited from a peri-urban district in Southern Ghana using purposive and snowball techniques in health facilities and communities respectively. The audio recorded interviews were transcribed verbatim and analysed manually using content analysis.

Results

Many pregnant adolescents are silent victims of a hash socio-economic environment, in which they experience significant financial deprivation, parental neglect and sexual abuse. Also, negative experiences of some adolescent girls such as scolding, flogging by parents, stigmatisation and rejection by peers and neighbors result in grieve, stress and contemplation of abortion and or suicide. However, adolescents did not consider abortion as the best option with regard to their pregnancy. Rather, family members provided adolescents with critical support as they devise strategies such as avoiding people, depending on God and praying to cope with their pregnancy.

Conclusion

Adolescent pregnancy occurred through consensual sex, transactional sex and sexual abuse. While parents provide support, pregnant adolescents self-isolate, depend on God and pray to cope with pregnancy and drop out of school. We recommend that the Ministries of Education and Health, and law enforcement agencies should engage community leaders and members, religious groups, non-governmental organisations and other key stakeholders to develop interventions aimed at supporting girls to complete at least Senior High School. While doing this, it is also important to provide support to victims of sexual abuse and punish perpetrators accordingly.
Primary care patients’ perspectives on the use of non-pharmacological home remedies in Geneva: a cross-sectional study
Authors: Winkler Neria E. , Sebo Paul , Haller Dagmar M. , Maisonneuve Hubert
Published: May 2022

Background

Home remedies are anchored in patients’ everyday life, but their use in Western cultures remains scarcely explored. Our objectives were to investigate primary care patients’ perspectives and use of non-pharmacological home remedies in Geneva (Switzerland).

Methods

In spring 2020, we conducted a cross-sectional survey among adult primary care patients in randomly selected general practices (N = 15). Patients were recruited in the waiting rooms and asked to complete a questionnaire about their sociodemographic characteristics, their home remedy use, and their expectations and reasons for using (or not using) home remedies. We employed descriptive statistics to summarise the data and logistic regression adjusted for clustering within practices to explore associations between home remedy use and participants’ sociodemographic characteristics.

Results

Three hundred fourteen of three hundred ninety patients agreed to participate in the study (participation rate 80.5%). Home remedies were used by 64.4% of patients. The main reasons given were for preventive purposes (55.3%), self-care (41.0%), as an alternative to conventional medicine (40.5%) and to avoid or delay a medical consultation (38.5%). One-third of patients considered that it was the GP’s role to spontaneously inform them about home remedies (36.4%), another third considered that it was the GP’s role to inform them, but only upon specific request (32.3%), and the last third of patients declared that it was not the GP’s role to provide information about home remedies (30.3%). Patients living in an urban zone (adjusted OR 2.1; 95%CI 1.0–4.4; p 0.05) and those with a tertiary education background (adjusted OR 1.9; 95%CI 1.0–3.6; p 0.05) believed that it was their GP’s role to inform them about home remedies.

Conclusions

Home remedies are used by a majority of primary care patients in Geneva. For a comprehensive and safe healthcare management in the context of patient-oriented medicine, more evidence-based research on efficacy and safety of home remedies as well as their place in primary care consultation is required.
Hybrid versus distance learning environment for a paediatric dentistry course and its influence on students’ satisfaction: a cross-sectional study
Authors: Yousry Yasmin Mohamed , Azab Maha Moussa
Published: May 2022

Background

During the novel COVID-19 pandemic, many universities adopted distance and hybrid learning as a modification to their teaching methods to ensure continuity of education, abiding by the worldwide recommendations of social distancing.

Aim

To compare learning environments created through hybrid learning versus distance learning, to deliver paediatric dentistry course, and to assess the correlation between the created learning environment and students’ satisfaction.

Method

In this cross-sectional study, students enrolled in a hybrid paediatric dentistry course were asked to participate in an electronic survey. The learning environment was assessed using Distance Educational Learning Environment Survey (DELES), students’ satisfaction was assessed using Satisfaction Scale (SS). Retrospective data for distance learning course was used for comparison. Ordinal data were compared using Mann-Whitney U test. Spearman’s rank order correlation coefficient was used to correlate students’ satisfaction with DELES. Multiple regression analysis was used to predict satisfaction.

Results

A total of 376 students’ data were considered in the study. Hybrid learning had significantly higher scores than distance learning in 3 DELES scales. There was a statistically significant weak positive correlation between satisfaction and DELES. Multiple regression analysis model was statistically significant and accounted for (22.8%) of the variance in students’ satisfaction. Only “Instructor support” (p = 0.001) and “Student autonomy” (p < 0.001) had a significant effect on satisfaction.

Conclusion

This study supports the superiority of a hybrid learning environment over a complete distance learning environment, it also shows that satisfaction is correlated and can be predicted by the created learning environment.

Trial registration

This study has been registered on clinicaltrials.gov on 21 May 2020 with an identifier: NCT04401371.
Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies
Authors: Perez-Cornago Aurora , Dunneram Yashvee , Watts Eleanor L. , Key Timothy J. , Travis Ruth C.
Published: May 2022

Background

The association of adiposity with prostate cancer specific mortality remains unclear. We examined how adiposity relates to fatal prostate cancer and described the cross-sectional associations of commonly used adiposity measurements with adiposity estimated by imaging in UK Biobank. We also conducted a dose-response meta-analysis to integrate the new data with existing prospective evidence.

Methods

218,237 men from UK Biobank who were free from cancer at baseline were included. Body mass index (BMI), total body fat percentage (using bioimpedance), waist circumference (WC) and waist-to-hip ratio (WHR) were collected at recruitment. Risk of dying from prostate cancer (primary cause) by the different adiposity measurements was estimated using multivariable-adjusted Cox proportional hazards models. Results from this and other prospective cohort studies were combined in a dose-response meta-analysis.

Results

In UK Biobank, 661 men died from prostate cancer over a mean follow-up of 11.6 years. In the subsample of participants with magnetic resonance imaging and dual-energy X-ray absorptiometry, BMI, body fat percentage and WC were strongly associated with imaging estimates of total and central adiposity (e.g. visceral fat, trunk fat). The hazard ratios (HR) for prostate cancer death were 1.07 (95% confidence interval = 0.97–1.17) per 5 kg/m2 higher BMI, 1.00 (0.94–1.08) per 5% increase in total body fat percentage, 1.06 (0.99–1.14) per 10 cm increase in WC and 1.07 (1.01–1.14) per 0.05 increase in WHR. Our meta-analyses of prospective studies included 19,633 prostate cancer deaths for BMI, 670 for body fat percentage, 3181 for WC and 1639 for WHR, and the combined HRs for dying from prostate cancer for the increments above were 1.10 (1.07–1.12), 1.03 (0.96–1.11), 1.07 (1.03–1.11), and 1.06 (1.01–1.10), respectively.

Conclusion

Overall, we found that men with higher total and central adiposity had similarly higher risks of prostate cancer death, which may be biologically driven and/or due to differences in detection. In either case, these findings support the benefit for men of maintaining a healthy body weight.
Effectiveness of oral care interventions on malodour in dogs
Authors: Croft Julie M. , Patel Krusha V. , Inui Taichi , Ruparell Avika , Staunton Ruth , Holcombe Lucy J.
Published: May 2022

Background

Oral malodour is identified by pet owners as an unpleasant inconvenience, but they may not recognise this likely indicates underlying disease. The primary cause of oral malodour relates to the presence of bacteria in the oral cavity often associated with gingivitis and periodontitis. The purpose of this study was to determine the effect of feeding two oral care chews with different textural properties on oral malodour and the proportion of bacterial species involved in the production of volatile sulphur compounds (VSCs).

Methods

Fourteen dogs (9 Petit Basset Griffon Vendéen (PBGV) and 5 Beagle dogs)participated in the randomised cross-over study for a total of 14 weeks. The cohort was divided into four groups with each exposed to a different intervention per week: chew A, chew B, tooth brushing control or a no intervention control. An induced malodour method was used to assess VSCs in breath samples using a portable gas chromatograph (OralChroma™). Microbiological samples (supragingival plaque and tongue coating scrapes) were analysed for VSC-producing bacteria using Oral Hydrogen Sulfide agar with lead acetate.

Results

VSCs were detected in the dogs’ breath samples and levels of hydrogen sulphide and methyl mercaptan were found to be reduced following an intervention. Chew B significantly reduced the levels of both hydrogen sulphide (p < 0.001) and methyl mercaptan (p < 0.05) compared to no intervention. Reductions in methyl mercaptan were also observed for chew A and tooth brushing but these were not statistically significant. When compared to no intervention, all interventions significantly reduced the total bacterial load and VSC producing bacterial load in plaque (p < 0.001). For tongue samples, only chew B significantly reduced the total bacterial load and VSC-producing bacterial load (p < 0.001) compared to no intervention.

Conclusions

By inducing oral malodour and subsequently applying the one-time interventions, significant reductions in the levels of VSCs were observed. The use of oral care chews texturally designed to deliver a deep, all-round cleaning action can be particularly effective at managing oral malodour in dogs, likely through an enhanced ability to remove bacteria.
Baseline T-lymphocyte and cytokine indices in sheep peripheral blood
Authors: Yang Jihui , Lv Yongxue , Zhu Yazhou , Li Shasha , Tao Jia , Chang Liangliang , Zhu Mingxing , Zhao Jiaqing , Wang Yana , Wu Changyou , Zhao Wei
Published: May 2022

Background

Sheep are an important livestock species worldwide and an essential large-animal model for animal husbandry and veterinary research. Understanding fundamental immune indicators, especially T-lymphocyte parameters, is necessary for research on sheep diseases and vaccines, to better understand the immune response to bacteria and viruses for reducing the use of antibiotics and improving the welfare of sheep. We randomly selected 36 sheep of similar ages to analyze cell-related immune indicators in peripheral blood mononuclear cells (PBMCs). The proportions of CD4+ and CD8+ T cells in PBMCs were detected by flow cytometry. We used Concanavalin A (Con A) and Phorbol-12-myristate-13-acetate (PMA)/Ionomycin to stimulate PBMCs, and measured the expression of IFN-γ, IL-4, and IL-17A using enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISpot). Simultaneously, PMA/Ionomycin/brefeldin A (BFA) was added to PBMCs, then the expression of IFN-γ, IL-4, and IL-17A was detected by flow cytometry after 4 h of culturing. In addition, we observed the proliferation of PBMCs stimulated with Con A for 3, 4, and 5 days.

Results

The proportions of CD4+ T lymphocytes (18.70 ± 4.21%) and CD8+ T lymphocytes (8.70 ± 3.65%) were generally consistent among individuals, with a CD4/CD8 ratio of 2.40 ± 0.79. PBMCs produced high levels of IFN-γ, IL-4, and IL-17A after stimulation with PMA/Ionomycin and Con A. Furthermore, PMA/Ionomycin stimulation of PBMC yielded significantly higher cytokine levels than Con A stimulation. Flow cytometry showed that the level of IFN-γ (51.49 ± 11.54%) in CD8+ T lymphocytes was significantly (p < 0.001) higher than that in CD4+ T lymphocytes (14.29 ± 3.26%); IL-4 (16.13 ± 6.81%) in CD4+ T lymphocytes was significantly (p < 0.001) higher than that in CD8+ T lymphocytes (1.84 ± 1.33%), There was no difference in IL-17A between CD4+ (2.83 ± 0.98%) and CD8+ T lymphocytes (1.34 ± 0.67%). The proliferation of total lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes continued to increase between days 3 and 5; however, there were no significant differences in proliferation between the cell types during the stimulation period.

Conclusions

Evaluating primary sheep immune indicators, especially T lymphocytes, is significant for studying cellular immunity. This study provided valuable data and theoretical support for assessing the immune response of sheep to pathogens and improving sheep welfare.
Gene model-related m6A expression levels predict the risk of preeclampsia
Authors: Li Yiwei , Chen Can , Diao Mengyuan , Wei Yanli , Zhu Ying , Hu Wei
Published: May 2022

Background

This is the first study to explore the potential functions and expression patterns of RNA N6-methyladenosine (m6A) and potential related genes in preeclampsia.

Methods

We identified two m6A modification patterns through unsupervised cluster analysis and validated them by principal component analysis. We quantified the relative abundance of specific infiltrating immunocytes using single-sample gene set enrichment analysis (ssGSEA) and the Wilcoxon test. To screen hub genes related to m6A regulators, we performed weighted gene coexpression network analysis. Functional enrichment analysis was conducted for differential signalling pathways and cellular processes. Preeclampsia patients were grouped by consensus clustering based on differentially expressed hub genes and the relationship between different gene-mediated classifications and clinical features.

Results

Two m6A clusters in preeclampsia, cluster A and cluster B, were determined based on the expression of 17 m6A modification regulators; ssGSEA revealed seven significantly different immune cell subtypes between the two clusters. A total of 1393 DEGs and nine potential m6A-modified hub genes were screened. We divided the patients into two groups based on the expression of these nine genes. We found that almost all the patients in m6A cluster A were classified into hub gene cluster 1 and that a lower gestational age may be associated with more m6A-associated events.

Conclusions

This study revealed that hub gene-mediated classification is consistent with m6A modification clusters for predicting the clinical characteristics of patients with preeclampsia. Our results provide new insights into the molecular mechanisms of preeclampsia.
LMWHs dosage and outcomes in acute pulmonary embolism with renal insufficiency, an analysis from a large real-world study
Authors: Wang Dingyi , Fan Guohui , Lei Jieping , Yang Yuanhua , Xu Xiaomao , Ji Yingqun , Yi Qun , Chen Hong , Hu Xiaoyun , Liu Zhihong , Mao Yimin , Zhang Jie , Shi Juhong , Zhang Zhu , Wu Sinan , Tao Xincao , Xie Wanmu , Wan Jun , Zhang Yunxia , Zhang Shuai , Zhen Kaiyuan , Zhang Zhonghe , Fang Baomin , Wang Chen , Zhai Zhenguo ,   On behalf of the China pUlmonary thromboembolism REgistry Study (CURES) investigators
Published: May 2022

Background

Renal function is associated with prognoses for acute pulmonary embolism (PE).

Objective

To investigate the application of anticoagulants and dosage of LMWH among patients with renal insufficiency (RI), and the association between LWMH dosage and the patients’ in-hospital outcomes.

Methods

Adult patients diagnosed with non-high risk acute PE from 2009 to 2015, with available data of creatinine clearance (CCr) were enrolled from a multicenter registry in China. Renal insufficiency (RI) was defined as CCr < 60 ml/min. LMWH dosage was converted into IU/kg daily dose and presented as adjusted dose (≤ 100 IU/kg/day) and conventional dose (> 100 IU/kg/day). All-cause death, PE-related death and bleeding events during hospitalization were analyzed as endpoints.

Results

Among the enrolled 5870 patients, RI occurred in 1311 (22.3%). 30 ≤ CCr < 60 ml/min was associated with higher rate of bleeding events and CCr < 30 ml/min was associated with all-cause death, PE-related death and major bleeding. Adjusted-dose LMWH was applied in 26.1% of patients with 30 ≤ CCr < 60 ml/min and in 26.2% of CCr < 30 ml/min patients. Among patients with RI, in-hospital bleeding occurred more frequently in those who were administered conventional dose of LMWH, compared with adjusted dose (9.2% vs 5.0%, p = 0.047). Adjusted dose of LMWH presented as protective factor for in-hospital bleeding (OR 0.62, 95%CI 0.27–1.00, p = 0.0496) and the risk of bleeding increased as length of hospital stay prolonged (OR 1.03, 95%CI 1.01–1.06, p = 0.0014).

Conclusions

The proportion of adjusted usage of LMWH was low. The application of adjusted-dose LMWH was associated with lower risk of in-hospital bleeding for RI patients, in real-world setting of PE treatment. Anticoagulation strategy for RI patients should be paid more attention and requires evidence of high quality.

Trial Registration

The CURES was registered in ClinicalTrias.gov, identifier number: NCT02943343.
Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway
Authors: Xiao Li , Li Xue , Cao Peilin , Fei Wei , Zhou Hao , Tang Na , Liu Yi
Published: May 2022

Background

Interleukin-6 (IL-6) has been reported to be critical in oral squamous cell carcinoma (OSCC). However, the set of pathways that IL-6 might activate in OSCC are not fully understood.

Methods

IL-6 and Sox4 expressions were first determined with RT-qPCR, ELISA, Western blot, or immunohistochemistry in OSCC tissues, and correlations between IL-6 and Sox4 expression and patient pathological characteristics were examined, and Kaplan–Meier approach was employed for evaluating the prognostic utility in OSCC patients. CCK-8, EdU stain and colony formation assays were utilized to test cell proliferation in vitro. Mechanistically, downstream regulatory proteins of IL-6 were verified through chromatin immunoprecipitation, luciferase reporter, pull-down, and the rescued experiments. Western blot was used for detecting protein expression. A nude mouse tumorigenicity assay was used to confirm the role of IL-6 and Sox4 in vivo.

Results

IL-6 was upregulated in OSCC tissues, and Sox4 expression was positively correlated with IL-6 expression. High IL-6 and Sox4 expression was closely related to tumor size, TNM stage, and a poorer overall survival. Besides, IL-6 could accelerate OSCC cell proliferation by activating inflammasome via JAK2/STAT3/Sox4/NLRP3 pathways in vitro and in vivo. Furthermore, STAT3 played as a transcription factor which positively regulated Sox4, and IL-6 promotes Sox4 expression by activating JAK2/STAT3 pathway. Moreover, through the rescue experiments, we further confirmed that IL-6 could promote proliferation and NLRP3 inflammasome activation via JAK2/STAT3/Sox4 pathway in OSCC cells. Finally, knockdown of Sox4 suppressed OSCC growth in vivo, and antagonized the acceleration of IL-6 on tumor growth.

Conclusions

We confirmed that IL-6 plays an oncogenic role in OSCC progression by activating JAK2/STAT3/Sox4/NLRP3 pathway, which might be the therapeutic targets for OSCC remedy.