bluuebunny/crossref_metadata_2025 huggingface dataset:
Portuguese version of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP): psychometric validation and prospective application for early functional outcomes at a single institution
Authors: Lourenço Danilo B. , Amaral Breno Santos , Alfer-Junior Wladimir , Vasconcellos Ana , Russo Fernanda , Sanchez-Salas Rafael , Bianco Bianca , Wagner Andrew A. , Chang Peter , Moschovas Marcio Covas , Lemos Gustavo Caserta , Carneiro Arie
Published: October 2020

Background

The Expanded Prostate Index Composite for Clinical Practice (EPIC-CP) is a short version of the original EPIC, developed to facilitate the instrument’s use in routine care. This study aimed to validate the EPIC-CP Portuguese version, and evaluate its role in presenting early functional outcomes of surgically treated prostate cancer patients at a Latin American referral center.

Methods

The EPIC-CP was self-administered prospectively and individually by all localized prostate cancer patients, before and after robotic-assisted radical prostatectomy, from March 2017 to June 2018 at a single institution. For validation, we used the Cronbach’s alpha coefficient to evaluate internal consistency. The EPIC-CP domains were compared before surgery, and 6 months and 12 months after surgery. Statistical analyses were performed using the student’s t test, and Wilcoxon and Friedman tests, with p values < 0.05 considered significant.

Results

One hundred and fifty two patients answered the EPIC-CP. The patients had a median age of 62.7 (± 8.5) years and prostate specific antigen level of 6.3 (± 4.6) ng/ml. The Cronbach’s alpha varied from 0.75 to 0.77 for all domains with good internal consistency, except for the “vitality/hormonal” domain, which had a score of 0.35. The domain evolution for the preoperative and 6-month postoperative groups revealed that the domains related to urinary continence and bowel worsened, and were increased during the first 6 months; however, this variation had no obvious clinical implications, and the irritative symptoms improved. Regarding the sexual domain, the scores worsened, and also increased over the first 6 months. The results of the confirmatory factor analysis were robust, with an explained variance of 0.951 and covariance of 0.929.

Conclusions

The Portuguese version of the EPIC-CP is a reliable and valid questionnaire for postoperative patients, and very useful to improve the knowledge of the early functional outcomes of men treated for prostate cancer.
The impact of multi-person virtual reality competitive learning on anatomy education: a randomized controlled study
Authors: Du Yi-Chun , Fan Shih-Chen , Yang Li-Cheng
Published: October 2020

Background

Anatomy is one of the core subjects in medical education. Students spend considerable time and effort on learning the requisite anatomy knowledge. This study explored the effect of a multiple-player virtual reality (VR) gaming system on anatomy learning.

Methods

18 participants were randomly assigned into 3 learning conditions: (1) a textbook reading control group (CG), (2) a single-player VR (SP) group; and (3) a multiple-player VR (MP) group. The participants studied anatomy for 5 days, and completed a multiple-choice test on Days 1, 5, and 12. In the VR environment, the participants used handheld controllers to move the simulated tissues. The mission of the game was to complete puzzles of a human body. The SP and MP groups filled out a motivation inventory on Day 5. The scores on the multiple-choice test, the correct assembly rates, and the motivation inventory scores were analyzed using the 2-way ANOVA or independent t-test to compare group differences.

Results

There was a significant interaction effect of group and timepoint (p = 0.003) in the multiple-choice test. In the CG, the scores on Day 1, Day 5, and Day 12 were significantly different (p < 0.001). The scores on Day 5 were significantly higher than those on Day 1 (p < 0.001). Although the scores declined slightly on Day 12, they were still significantly higher than those on Day 1 (p < 0.001). The SP and MP groups had similar results (p < 0.001, p < 0.001). The differences between the groups were only significant on Day 12 (p = 0.003), not Day 5 (p = 0.06). On Day 12, the scores of the MP group were higher than those of the CG (p = 0.002). The SP group and MP group had high scores on the interest, competence, and importance subscales of the motivation inventory. Both VR groups considered the system to be fun and beneficial to their learning. However, the MP group reported higher stress levels than the SP group.

Conclusion

The results indicated that the proposed VR learning system had a positive impact on the anatomy learning. Although the between-player competition caused higher stress levels for the VR groups, the stress could have been a mediator of their learning outcomes.

Trial registration

ETRD, ETRD-D-19-00573. Registered 20 December 2018, http://www.edah.org.tw/irb/index.htm
Assessment of burnout in medical students using the Maslach Burnout Inventory-Student Survey: a cross-sectional data analysis
Authors: Obregon Michael , Luo Jessica , Shelton Jarod , Blevins Terri , MacDowell Martin
Published: October 2020

Background

Medical student burnout can cause emotional and physical exhaustion and detachment. The objectives of this study were to evaluate burnout using the Maslach Burnout Inventory-Student Survey (MBI-SS), identify factors that may predict burnout, and assess wellness initiatives effectiveness at reducing burnout.

Methods

The MBI-SS was administered to all medical students (Classes 2019 to 2022) at the University of Illinois College of Medicine (UICOM) from February to May 2019. Factor analysis and internal consistency of the MBI-SS were assessed. Mean MSBI-SS subscale scores for burnout were calculated for cynicism (CY), emotional exhaustion (EE), and academic efficacy (AE). Multiple regression analysis was used to identify student factors that may predict burnout.

Results

A total of 273 (21.6%) UICOM students completed the survey and 110 (40.3%) respondents reported self-perceived burnout. MBI-SS subscale scores were significantly higher for CY and EE, and significantly lower for AE in students who reported suffering from burnout versus students who did not report burnout. Mean ± SD subscale scores for CY, EE, and AE in burnout students were 14.44 ± 5.59, 23.23 ± 4.74, and 24.81 ± 5.35, respectively. In comparison, mean ± SD subscale scores for CY, EE, and AE in non-burnout students were 7.59 ± 5.16, 14.96 ± 5.71, and 28.74 ± 3.21, respectively. Regression analysis denoted significant associations between burnout and being out-of-phase in the curriculum, the effectiveness of wellness initiatives, and strength of motivation for medical school (SMMS) in both the two- and three-dimensional MBI-SS models. Gender was significantly associated with burnout in only the two-dimensional model.

Conclusions

Self-reported burnout in medical students at UICOM was validated using the MBI-SS. Being out-of-phase in the curriculum, being female, rating wellness initiatives as less effective, and demonstrating lower motivation for continued medical school education may be used as predictors of medical student burnout. This investigation may act as a guide for measuring burnout in medical student populations and how the implementation of wellness initiatives may ameliorate burnout.
Anxiety, perceived stress and coping strategies in nursing students: a cross-sectional, correlational, descriptive study
Authors: Onieva-Zafra María Dolores , Fernández-Muñoz Juan José , Fernández-Martínez Elia , García-Sánchez Francisco José , Abreu-Sánchez Ana , Parra-Fernández María Laura
Published: October 2020

Background

For many nursing students, clinical training represents a stressful experience. The levels of stress and anxiety may vary during students’ educational training, depending on their ability to adopt behavioral strategies for coping with stress, and other factors. This study aimed to investigate the relationship between anxiety, perceived stress, and the coping strategies used by nursing students during their clinical training.

Methods

A cross-sectional correlational descriptive study. The sample consisted of 190 nursing students enrolled in the Nursing Faculty of Ciudad Real University in Spain. Participants provided data on background characteristics and completed the following instruments: the Perceived Stress Scale; the State-Trait Anxiety Inventory and the Coping Behavior Inventory. Relationships between scores were examined using Spearman’s rho.

Results

The mean age of participants was 20.71 ± 3.89 years (range 18–46 years). Approximately half of the students (47.92%) indicated a moderate level of stress with a mean Perceived Stress Scale score of 22.78 (±8.54). Senior nursing students perceived higher levels of stress than novice students. The results showed a significant correlation for perceived stress and state anxiety (r = 0.463, p < .000) and also for trait anxiety (r = 0.718, p < .000). There was also a significant relationship between the total amount of perceived stress and the following domains of the coping behavior inventory: problem solving (r = −.452, p < .01), self-criticism (r = .408 p < .01), wishful thinking (r = .459, p < .01), social support(r = −.220, p < .01), cognitive restructuring (r = −.375, p < .01), and social withdrawal (r = .388, p < .01). In the current study, the coping strategy most frequently used by students was problem-solving, followed by social support and cognitive restructuring.

Conclusions

Nursing students in our study presented a moderate level of stress, in addition there was a significant correlation with anxiety. Nursing teachers and clinical preceptors/mentors should be encouraged to develop programs to help prepare nursing students to cope with the challenges they are about to face during their clinical placements.
A qualitative study of big data and the opioid epidemic: recommendations for data governance
Authors: Evans Elizabeth A. , Delorme Elizabeth , Cyr Karl , Goldstein Daniel M.
Published: October 2020

Background

The opioid epidemic has enabled rapid and unsurpassed use of big data on people with opioid use disorder to design initiatives to battle the public health crisis, generally without adequate input from impacted communities. Efforts informed by big data are saving lives, yielding significant benefits. Uses of big data may also undermine public trust in government and cause other unintended harms.

Objectives

We aimed to identify concerns and recommendations regarding how to use big data on opioid use in ethical ways.

Methods

We conducted focus groups and interviews in 2019 with 39 big data stakeholders (gatekeepers, researchers, patient advocates) who had interest in or knowledge of the Public Health Data Warehouse maintained by the Massachusetts Department of Public Health.

Results

Concerns regarding big data on opioid use are rooted in potential privacy infringements due to linkage of previously distinct data systems, increased profiling and surveillance capabilities, limitless lifespan, and lack of explicit informed consent. Also problematic is the inability of affected groups to control how big data are used, the potential of big data to increase stigmatization and discrimination of those affected despite data anonymization, and uses that ignore or perpetuate biases. Participants support big data processes that protect and respect patients and society, ensure justice, and foster patient and public trust in public institutions. Recommendations for ethical big data governance offer ways to narrow the big data divide (e.g., prioritize health equity, set off-limits topics/methods, recognize blind spots), enact shared data governance (e.g., establish community advisory boards), cultivate public trust and earn social license for big data uses (e.g., institute safeguards and other stewardship responsibilities, engage the public, communicate the greater good), and refocus ethical approaches.

Conclusions

Using big data to address the opioid epidemic poses ethical concerns which, if unaddressed, may undermine its benefits. Findings can inform guidelines on how to conduct ethical big data governance and in ways that protect and respect patients and society, ensure justice, and foster patient and public trust in public institutions.
Genetic testing for breast cancer risk, from BRCA1/2 to a seven gene panel: an ethical analysis
Authors: Gustavsson Erik , Galvis Giovanni , Juth Niklas
Published: October 2020

Background

Genetic testing is moving from targeted investigations of monogenetic diseases to broader testing that may provide more information. For example, recent health economic studies of genetic testing for an increased risk of breast cancer suggest that it is associated with higher cost-effectiveness to screen for pathogenic variants in a seven gene panel rather than the usual two gene test for variants in BRCA1 and BRCA2. However, irrespective of the extent to which the screening of the panel is cost-effective, there may be ethical reasons to not screen for pathogenic variants in a panel, or to revise the way in which testing and disclosing of results are carried out.

Main text

In this paper we discuss the ethical aspects of genetic testing for an increased risk of breast cancer with a special focus on the ethical differences between screening for pathogenic variants in BRCA1/2 and a seven gene panel. The paper identifies that the panel increases the number of secondary findings as well as the number of variants of uncertain significance as two specific issues that call for ethical reflection.

Conclusions

We conclude that while the problem of handling secondary findings should not be overstated with regard to the panel, the fact that the panel also generate more variants of uncertain significance, give rise to a more complex set of problems that relate to the value of health as well as the value of autonomy. Therefore, it is insufficient to claim that the seven gene panel is preferable by only referring to the higher cost effectiveness of the panel.
Sustainable waiting time reductions after introducing the STAT model for access and triage: 12-month follow up of a stepped wedge cluster randomised controlled trial
Authors: Harding Katherine E. , Snowdon David A. , Prendergast Luke , Lewis Annie K. , Kent Bridie , Leggat Sandy F. , Taylor Nicholas F.
Published: October 2020

Background

Timely access is a challenge for providers of outpatient and community-based health services, as seen by the often lengthy waiting lists to manage demand. The Specific Timely Appointments for Triage (STAT) model, an alternative approach for managing access and triage, reduced waiting time by 34% in a stepped wedge cluster randomised controlled trial involving 8 services and more than 3000 participants. Follow up periods ranged from 3 to 10 months across the participating services in accordance with the stepped wedge design. This study aimed to determine whether outcomes were sustained for a full 12 months after implementation of the STAT model at each site.

Methods

Routinely collected service data were obtained for a total of 12 months following implementation of the STAT model at each of the 8 services that participated in a stepped wedge cluster randomised controlled trial. The primary outcome was time to first appointment. Secondary outcomes included non-attendance rates, time to second appointment and service use over 12 weeks. Outcomes were compared to pre-intervention data from the original trial, modelled using generalised linear mixed effects models accounting for clustering of sites.

Results

A 29% reduction in waiting time could be attributed to STAT over 12 months, compared to 34% in the original trial. A reduction in variability in waiting time was sustained. There were no significant changes in time to second appointment or in the number of missed appointments in the extended follow up period.

Conclusions

STAT is an effective strategy for reducing waiting time in community-based outpatient services. At 12 months, small reductions in the overall effect are apparent, but reductions in variability are sustained, suggesting that people who previously waited the longest benefit most from the STAT model.

Trial registration

This is a 12-month follow up of a stepped wedge cluster randomised controlled trial that was registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12615001016527).
Costs and healthcare utilisation of patients with heart failure in Spain
Authors: Escobar Carlos , Varela Luis , Palacios Beatriz , Capel Margarita , Sicras Antoni , Sicras Aram , Hormigo Antonio , Alcázar Roberto , Manito Nicolás , Botana Manuel
Published: October 2020

Background

Increasing the knowledge about heart failure (HF) costs and their determinants is important to ascertain how HF management can be optimized, leading to a significant decrease of HF costs. This study evaluated the cumulative costs and healthcare utilisation in HF patients in Spain.

Methods

Observational, retrospective, population-based study using BIG-PAC database, which included data from specialized and primary care of people ≥18 years, from seven autonomous communities in Spain, who received care for HF between 2015 and 2019. The healthcare and medication costs were summarized on a yearly basis starting from the index date (1st January 2015), and then cumulatively until 2019.

Results

We identified 17,163 patients with HF (year 2015: mean age 77.3 ± 11.8 years, 53.5% men, 51.7% systolic HF, 43.6% on NYHA functional class II). During the 2015–2019 period, total HF associated costs reached 15,373 Euros per person, being cardiovascular disease hospitalizations the most important determinant (75.8%), particularly HF hospitalizations (51.0%). Total medication cost accounted for 7.0% of the total cost. During this period, there was a progressive decrease of cardiovascular disease hospital costs per year (from 2834 Euros in 2015 to 2146 Euros in 2019, P < 0.001), as well as cardiovascular and diabetic medication costs.

Conclusions

During the 2015–2019 period, costs of HF patients in Spain were substantial, being HF hospitalizations the most important determinant. Medication costs represented only a small proportion of total costs. Improving HF management, particularly through the use of drugs that reduce HF hospitalization may be helpful to reduce HF burden.
Genomic amplification of chromosome 20q13.33 is the early biomarker for the development of sporadic colorectal carcinoma
Authors: Bui Vo-Minh-Hoang , Mettling Clément , Jou Jonathan , Sun H. Sunny
Published: October 2020

Background

Colorectal carcinoma (CRC) is the third most common cancer in the world and also the third leading cause of cancer-related mortality in Taiwan. CRC tumorigenesis is a multistep process, starting from mutations causing loss of function of tumor suppressor genes, canonically demonstrated in adenomatous polyposis coli pathogenesis. Although many genes or chromosomal alterations have been shown to be involved in this process, there are still unrecognized molecular events within CRC tumorigenesis. Elucidating these mechanisms may help improve the management and treatment.

Methods

In this study, we aimed to identify copy number alteration of the smallest chromosomal regions that is significantly associated with sporadic CRC tumorigenesis using high-resolution array-based Comparative Genomic Hybridization (aCGH) and quantitative Polymerase chain reaction (qPCR). In addition, microsatellite instability assay and sequencing-based mutation assay were performed to illustrate the initiation event of CRC tumorigenesis.

Results

A total of 571 CRC patients were recruited and 377 paired CRC tissues from sporadic CRC cases were used to define the smallest regions with chromosome copy number changes. In addition, 198 colorectal polyps from 160 patients were also used to study the role of 20q13.33 gain in CRC tumorigenesis. We found that gain in 20q13.33 is the main chromosomal abnormalities in this patient population and counts 50.9 and 62.8% in CRC and colon polyps, respectively. Furthermore,APCandKRASgene mutations were profiled simultaneously and co-analyzed with microsatellite instability and 20q13.33 gain in CRC patients. Our study showed that the frequency of 20q13.33 copy number gain was highest among all reported CRC mutations.

Conclusion

AsAPCorKRASmutations are currently identified as the most important targets for CRC therapy, this study proposes that 20q13.33 copy number gain and the associated chromosomal genes function as promising biomarkers for both early stage detection and targeted therapy of sporadic CRCs in the future.
Global trend of diabetes mortality attributed to vascular complications, 2000–2016
Authors: Ling Wei , Huang Yi , Huang Yan-Mei , Fan Rong-Rong , Sui Yi , Zhao Hai-Lu
Published: October 2020

Background

The global epidemic of diabetes mellitus continues to grow and affects developed and developing countries alike. Intensive glycemic control is thought to modify the risks for vascular complications, hence the risks for diabetes-related death. We investigated the trend of diabetic vascular complication-related deaths between 2000 and 2016 in the global diabetes landscape.

Methods

We collected 17 years of death certificates data from 108 countries in the World Health Organization mortality database between 2000 and 2016, with coding for diabetic complications. Crude and age-standardized proportions and rates were calculated. Trend analysis was done with annual average percentage change (AAPC) of rates computed by joinpoint regression.

Results

From 2000 through 2016, 7,108,145 deaths of diabetes were reported in the 108 countries. Among them, 26.8% (1,904,787 cases) were attributed to vascular complications in damaged organs, including the kidneys (1,355,085 cases, 71.1%), peripheral circulatory (515,293 cases, 27.1%), nerves (28,697 cases, 1.5%) and eyes (5751 cases, 0.3%). Overall, the age-standardized proportion of vascular complication-related mortality was 267.8 [95% confidence interval (95% CI), 267.5–268.1] cases per 1000 deaths and the rate was 53.6 (95% CI 53.5–53.7) cases per 100,000 person-years. Throughout the 17-year period, the overall age-standardized proportions of deaths attributable to vascular complications had increased 37.9%, while the overall age-standardized mortality rates related to vascular complications had increased 30.8% (AAPC = 1.9% [1.4–2.4%, p < 0.05]). These increases were predominantly driven by a 159.8% increase in the rate (AAPC = 2.7% [1.2–4.3%, p < 0.05]) from renal complications. Trends in the rates and AAPC of deaths varied by type of diabetes and of complications, as well as by countries, regions and domestic income.

Conclusion

Diabetic vascular complication-related deaths had increased substantially during 2000–2016, mainly driven by the increased mortality of renal complications.
CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling
Authors: Hu Ben-Shun , Tang Tian , Jia Jun-Li , Xie Bi-Chen , Wu Tie-Long , Sheng Ying-Yue , Xue Yu-Zheng , Tang Hua-Min
Published: October 2020

Background

CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied.

Methods

Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-β, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry.

Results

Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells.

Conclusion

Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.
RAM-589.555 favors neuroprotective and anti-inflammatory profile of CNS-resident glial cells in acute relapse EAE affected mice
Authors: Zilkha-Falb Rina , Rachutin-Zalogin Tatyana , Cleaver Lakota , Gurevich Michael , Achiron Anat
Published: October 2020

Background

Targeting RNA polymerase-1 (POL1) machinery is a new strategy for suppression of multiple sclerosis (MS) relapse activity. Oral administration of POL1 inhibitor RAM-589.555, which is characterized by high permeability and bioavailability in naïve mice, ameliorates proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) by suppressing activated autoreactive lymphocytes. We assessed the accessibility of RAM-589.555 to the central nervous system (CNS) of EAE-mice and further investigated its immunomodulatory effects on CNS-resident astro- and micro-glial cells in-vitro and in-vivo.

Methods

Effects of RAM-589.555 on activated microglia and astrocyte viability, proliferation, and secretion of neurotrophic factors were assessed in-vitro. The pharmacokinetic of RAM-589.555 was evaluated in the blood and central nervous system (CNS) of EAE-affected mice. High-dimensional single-cell mass cytometry was applied to characterize the effect of RAM-589.555 on EAE-affected mice’s CNS-resident micro- and astroglial cells and CNS-infiltrating immune cells, which were obtained seven days after RAM-589.555 administration at EAE onset. Simultaneously, the expression level of pre-rRNA, the POL1 end product, was assessed in blood cells, microglia, and astrocytes to monitor RAM-589.555 effects.

Results

RAM-589.555 demonstrated blood and CNS permeability in EAE mice. In-vitro, incubation with 400 nM of RAM-589.555 significantly reduced viability and proliferation of lipopolysaccharide (LPS)-activated microglia by 70% and 45% (p< 0.05), respectively, while tumor necrosis factor α (TNFα)-activated astrocytes were not affected. The secretion of neurotrophic factors was preserved. Furthermore, 7 days after administration of RAM-589.555 at EAE onset, the level of pre-rRNA transcript in peripheral blood mononuclear cells (PBMC) was decreased by 38.6% (p= 0.02), while levels of pre-rRNA transcript in microglia and astrocytes remained unchanged. The high-dimensional single-cell mass cytometry analysis showed decreased percentages of CNS-resident microglia and astrocytes, diminished pro-inflammatory cytokines (IL-1β, IL-6, IL-12, IL-17, TNFα, and IFNγ), and an increase of their anti-inflammatory cytokines (IL-4, IL-10, and TGFβ) in RAM-589.555-treated compared to vehicle-treated mice (p< 0.05).

Conclusions

These data correlate RAM-589.555-induced clinical amelioration and its CNS-permeability to decreased CNS-inflammation, and decreased micro- and astrogliosis, while restoring micro- and astroglial anti-inflammatory and neuroprotective capacity.
Even lobar deposition of poorly soluble gold nanoparticles (AuNPs) is similar to that of soluble silver nanoparticles (AgNPs)
Authors: Kim Hoi Pin , Kim Jin Kwon , Jo Mi Seong , Park Jung Duck , Ahn Kangho , Gulumian Mary , Oberdörster Günter , Yu Il Je
Published: October 2020

Background

Information on particle deposition, retention, and clearance is important when evaluating the risk of inhaled nanomaterials to human health. The revised Organization Economic Cooperation and Development (OECD) inhalation toxicity test guidelines now require lung burden measurements of nanomaterials after rodent subacute and sub-chronic inhalation exposure (OECD 412, OECD 413) to inform on lung clearance behavior and translocation after exposure and during post-exposure observation (PEO). Lung burden measurements are particularly relevant when the testing chemical is a solid poorly soluble nanomaterial. Previously, the current authors showed that total retained lung burden of inhaled soluble silver nanoparticles (AgNPs) could be effectively measured using any individual lung lobe.

Methods and results

Accordingly, the current study investigated the evenness of deposition/retention of poorly soluble gold nanoparticles (AuNPs) after 1 and 5 days of inhalation exposure. Rats were exposed nose-only for 1 or 5 days (6 h/day) to an aerosol of 11 nm well-dispersed AuNPs. Thereafter, the five lung lobes were separated and the gold concentrations measured using an inductively coupled plasma-mass spectrophotometer (ICP-MS). The results showed no statistically significant difference in the AuNP deposition/retention among the different lung lobes in terms of the gold mass per gram of lung tissue.

Conclusions

Thus, it would seem that any rat lung lobe can be used for the lung burden analysis after short or long-term NP inhalation, while the other lobes can be used for collecting and analyzing the bronchoalveolar lavage fluid (BALF) and for the histopathological analysis. Therefore, combining the lung burden measurement, histopathological tissue preparation, and BALF assay from one rat can minimize the number of animals used and maximize the number of endpoints measured.
Exploring anti-corruption, transparency, and accountability in the World Health Organization, the United Nations Development Programme, the World Bank Group, and the Global Fund to Fight AIDS, Tuberculosis and Malaria
Authors: Kohler Jillian Clare , Bowra Andrea
Published: October 2020

Corruption is recognized by the global community as a threat to development generally and to achieving health goals, such as the United Nations Sustainable Development Goal # 3: ensuring healthy lives and promoting well-being for all. As such, international organizations such as the World Health Organizations and the United Nations Development Program are creating an evidence base on how best to address corruption in health systems. At present, the risk of corruption is even more apparent, given the need for quick and nimble responses to the COVID-19 pandemic, which may include a relaxation of standards and the rapid mobilization of large funds. As international organizations and governments attempt to respond to the ever-changing demands of this pandemic, there is a need to acknowledge and address the increased opportunity for corruption.

In order to explore how such risks of corruption are addressed in international organizations, this paper focuses on the question: How are international organizations implementing measures to promote accountability and transparency, and anti-corruption, in their own operations? The following international organizations were selected as the focus of this paper given their current involvement in anti-corruption, transparency, and accountability in the health sector: the World Health Organization, the United Nations Development Program, the World Bank Group, and the Global Fund to Fight Aids, Tuberculosis and Malaria. Our findings demonstrate that there has been a clear increase in the volume and scope of anti-corruption, accountability, and transparency measures implemented by these international organizations in recent years. However, the efficacy of these measures remains unclear. Further research is needed to determine how these measures are achieving their transparency, accountability, and anti-corruption goals.
Bamboos for weaving and relevant traditional knowledge in Sansui, Southwest China
Authors: Luo Binsheng , Ahmed Selena , Long Chunlin
Published: October 2020

Background

Traditional bamboo weaving has been practiced for centuries in Sansui, a county dominated by the Miao people, in Guizhou province of Southwest China. Sansui bamboo weaving represents an intangible cultural heritage as defined by UNESCO, but, like many other traditional handicrafts in China, it has suffered a downfall in this period of rapid development. Sansui bamboo weaving is now experiencing a renaissance due to the joint efforts of the local government, bamboo weaving companies, and individual bamboo weavers. However, what bamboo species have supported the traditional bamboo weaving in Sansui keeps unknown up to now. The traditional knowledge and technology associated with bamboo weaving have not been reported. In addition, the resumption of the local bamboo industry may provide some valuable experiences for other downfallen traditional handicrafts or local communities. Thus, an ethnobotanical study on Sansui bamboo weaving has been carried out.

Methods

This study mainly used ethnobotanical methods, including key informant interviews and participatory observations. Different stakeholders were selected by applying the snowball method as our key informants including 6 officials, 37 bamboo weavers, and 17 bamboo and bamboo weaving product merchants. We also went into the local weavers’ houses to visit the whole weaving process. The bamboo and dye plant species for bamboo weaving were identified by taxonomists and referring to online databases available.

Results

Based on field investigations, 17 bamboo species used for weaving were recorded. Different bamboo species were woven for different purposes based on their own characters. Phyllostachys heteroclada is the most popular species locally. Bamboo strips are usually dyed by using Platycarya strobilacea and Rubia cordifolia to be made for different images. In recent years, the size, functions, and materials of local bamboo weaving crafts as well as their market mode have been changed to adapt to new development trends and to cater to the market. In addition, the cooperation among bamboo weavers, bamboo companies, and household workshops has provided great support to the local bamboo industry and to reboot the economy of the local community. Some suggestions for the sustainable economic development of Sansui bamboo weaving and other Chinese traditional handicrafts are proposed.

Conclusion

In the present study, the bamboo weaving-associated traditional knowledge was collected by means of ethnobotanical methods. The recent renaissance of the bamboo weaving business in Sansui can be attributed both to government support and the innovations of the bamboo weaving industry itself. The developing mode (“Internet + intangible cultural heritage + poverty alleviation”), which combined the internet, poverty alleviation, and intangible cultural heritage, is valid and worth being promoted.
Incidence of intraspinal abnormalities in congenital scoliosis: a systematic review and meta-analysis
Authors: Wang Xudong , Yu Yangke , Yang Ningning , Xia Lei
Published: October 2020

Objective

This is the first systematic review and meta-analysis on the overall incidence of intraspinal abnormalities in patients with congenital scoliosis (CS) and potential influencing factors.

Methods

We searched three large electronic databases (PubMed, EMBASE, and Cochrane Library) for potentially relevant studies. The quality of the included studies was assessed independently by two authors using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Data on the number of CS patients, number of CS patients with intraspinal abnormalities, sex of the patients, and CS types were extracted from the included studies. R software was used to pool and analyze all the extracted data.

Results

This meta-analysis included 10 articles, and 671 of 1863 CS patients undergoing magnetic resonance imaging (MRI) examinations were identified to have intraspinal abnormalities. The overall incidence of intraspinal abnormalities in the patients with CS was 37% (95% CI, 29–45%). Diastematomyelia was the most common intraspinal abnormality and was detected in 45.60% of the patients with intraspinal abnormalities (306/671). The remaining intraspinal abnormalities included syringomyelia (273/671, 40.69%), tethered cord (190/671, 28.32%), low conus (58/671, 8.64%), intraspinal mass (39/671, 5.81%), Chiari malformation (32/671, 4.77%), fatty filum (27/671, 4.02%), spina bifida (occulta excluded) (17/671, 2.53%), tumor (17/671, 2.53%), cyst (12/671, 1.79%), syringomyelus (4/671, 0.60%), dural ectasia (1/671, 0.15%), and undiagnosed cord MRI hyperintensity (1/671, 0.15%). The patient’s sex and CS type were not factors that affected the incidence of intraspinal abnormalities in CS patients (allP> 0.05).

Conclusions

This meta-analysis revealed that the overall incidence of intraspinal abnormalities detected by MRI in CS patients was 37%. Diastematomyelia was the most common intraspinal abnormality. The patient’s sex and CS type were not factors that affected the incidence of intraspinal abnormalities in CS patients.
Hypoxia-autophagy axis induces VEGFA by peritoneal mesothelial cells to promote gastric cancer peritoneal metastasis through an integrin α5-fibronectin pathway
Authors: Wang Xiaoxun , Che Xiaofang , Yu Yang , Cheng Yu , Bai Ming , Yang Zichang , Guo Qiqiang , Xie Xiaochen , Li Danni , Guo Min , Hou Kezuo , Guo Wendong , Qu Xiujuan , Cao Liu
Published: October 2020

Background

Peritoneal metastasis (PM) is an important pathological process in the progression of gastric cancer (GC). The metastatic potential of tumor and stromal cells is governed by hypoxia, which is a key molecular feature of the tumor microenvironment. Mesothelial cells also participate in this complex and dynamic process. However, the molecular mechanisms underlying the hypoxia-driven mesothelial-tumor interactions that promote peritoneal metastasis of GC remain unclear.

Methods

We determined the hypoxic microenvironment in PM of nude mice by immunohistochemical analysis and screened VEGFA by human growth factor array kit. The crosstalk mediated by VEGFA between peritoneal mesothelial cells (PMCs) and GC cells was determined in GC cells incubated with conditioned medium prepared from hypoxia-treated PMCs. The association between VEGFR1 and integrin α5 and fibronectin in GC cells was enriched using Gene Set Enrichment Analysis and KEGG pathway enrichment analysis. In vitro and xenograft mouse models were used to evaluate the impact of VEGFA/VEGFR1 on gastric cancer peritoneal metastasis. Confocal microscopy and immunoprecipitation were performed to determine the effect of hypoxia-induced autophagy.

Results

Here we report that in the PMCs of the hypoxic microenvironment, SIRT1 is degraded via the autophagic lysosomal pathway, leading to increased acetylation of HIF-1α and secretion of VEGFA. Under hypoxic conditions, VEGFA derived from PMCs acts on VEGFR1 of GC cells, resulting in p-ERK/p-JNK pathway activation, increased integrin α5 and fibronectin expression, and promotion of PM.

Conclusions

Our findings have elucidated the mechanisms by which PMCs promote PM in GC in hypoxic environments. This study also provides a theoretical basis for considering autophagic pathways or VEGFA as potential therapeutic targets to treat PM in GC.
Correction to: Graphing and reporting heterogeneous treatment effects through reference classes
Authors: Watson James A. , Holmes Chris C.
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab
Authors: Strand Vibeke , Boklage Susan H. , Kimura Toshio , Joly Florence , Boyapati Anita , Msihid Jérôme
Published: October 2020

Background

Increased levels of cytokines, including interleukin-6 (IL-6), reflect inflammation and have been shown to be predictive of therapeutic responses, fatigue, pain, and depression in patients with rheumatoid arthritis (RA), but limited data exist on associations between IL-6 levels and health-related quality of life (HRQoL). This post hoc analysis of MONARCH phase III randomized controlled trial data evaluated the potential of baseline IL-6 levels to differentially predict HRQoL improvements with sarilumab, a fully human monoclonal antibody directed against both soluble and membrane-bound IL-6 receptor α (anti-IL-6Rα) versus adalimumab, a tumor necrosis factor α inhibitor, both approved for treatment of active RA.

Methods

Baseline serum IL-6 levels in 300/369 randomized patients were categorized into low (1.6–7.1 pg/mL), medium (7.2–39.5 pg/mL), and high (39.6–692.3 pg/mL) tertiles. HRQoL was measured at baseline and week (W)24 and W52 by Short Form 36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores, Functional Assessment of Chronic Illness Therapy -fatigue, and duration of morning stiffness visual analog scale (AM-stiffness VAS). Linear regression of changes from baseline in HRQoL (IL-6 tertile, treatment, region as a stratification factor, and IL-6 tertile-by-treatment interaction as fixed effects) assessed predictivity of baseline IL-6 levels, with low tertile as reference. Pairwise comparisons of improvements between treatment groups were performed by tertile; least squares mean differences and 95% CIs were calculated. Similar analyses evaluated W24 patient-level response on minimum clinically important differences (MCID).

Results

At baseline, patients with high versus medium or low IL-6 levels (n = 100, respectively) reported worse (nominal p < 0.05) SF-36 MCS and role-physical, bodily pain, social functioning, role-emotional domain, and AM-stiffness VAS scores. There was a greater treatment effect with sarilumab versus adalimumab in high tertile versus low tertile groups in SF-36 PCS, physical functioning domain, and AM-stiffness VAS (nominal interaction p < 0.05). PCS improvements ≥MCID were higher in high (odds ratio [OR] 6.31 [2.37, 16.81]) versus low (OR 0.97 [0.43, 2.16]) tertiles with sarilumab versus adalimumab (nominal interaction p < 0.05). Adverse events between IL-6 tertiles were similar.

Conclusions

Patients with high baseline IL-6 levels reported better improvements in PCS, physical functioning domain, and AM-stiffness scores with sarilumab versus adalimumab and safety consistent with IL-6R blockade.

Trial registration

NCT02332590. Registered on 5 January 2015
Postural control in top-level female volleyball players
Authors: Borzucka Dorota , Kręcisz Krzysztof , Rektor Zbigniew , Kuczyński Michał
Published: October 2020

Background

The aim of this study was to compare the postural control of the Poland national women’s volleyball team players with a control group of non-training young women. It was hypothesized that volleyball players use a specific balance control strategy due to the high motor requirements of their team sport.

Methods

Static postural sway variables were measured in 31 athletes and 31 non-training women. Participants were standing on a force plate with eyes open, and their center of pressure signals were recorded for the 20s with the sampling rate of 20 Hz in the medial-lateral (ML) and anterior-posterior (AP) planes.

Results

In both AP and ML planes, athletes had lower range and higher fractal dimension of the COP. They had also higher peak frequency than control group in the ML plane only. The remaining COP indices including variability, mean velocity and mean frequency did not display any intergroup differences.

Conclusion

It can be assumed that due to the high motor requirements of their sport discipline Polish female volleyball players have developed a unique posture control. On the court they have to distribute their sensory resources optimally between balance control and actions resulting from the specifics of the volleyball game. There are no clearly defined criteria for optimal postural strategies for elite athletes, but they rather vary depending on a given sport. The results of our research confirm this claim.

Trial registration

The tests were previously approved by the Bioethical Commission of the Chamber of Physicians in Opole. (Resolution No. 151/13.12.2007). This study adheres to the CONSORT guidelines.
Brain function distinguishes female carriers and non-carriers of familial risk for autism
Authors: Eggebrecht Adam T. , Dworetsky Ally , Hawks Zoë , Coalson Rebecca , Adeyemo Babatunde , Davis Savannah , Gray Daniel , McMichael Alana , Petersen Steven E. , Constantino John N. , Pruett John R.
Published: October 2020

Background

Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed (“carrier”) females.

Methods

Using functional magnetic resonance imaging, we examined brain responses to passive viewing of point light displays—depicting biological versus non-biological motion—in a sample of undiagnosed adult females enriched for inherited susceptibility to ASD on the basis of affectation in their respective family pedigrees. Brain responses in carrier females were compared to responses in age-, SRS-, and IQ-matched non-carrier-females—i.e., females unrelated to individuals with ASD. We conducted a hypothesis-driven analysis focused on previously published regions of interest as well as exploratory, brain-wide analyses designed to characterize more fully the rich responses to this paradigm.

Results

We observed robust responses to biological motion. Notwithstanding, the 12 regions implicated by prior research did not exhibit the hypothesized interaction between group (carriers vs. controls) and point light displays (biological vs. non-biological motion). Exploratory, brain-wide analyses identified this interaction in three novel regions. Post hoc analyses additionally revealed significant variations in the time course of brain activation in 20 regions spanning occipital and temporal cortex, indicating group differences in response to point light displays (irrespective of the nature of motion) for exploration in future studies.

Limitations

We were unable to successfully eye-track all participants, which prevented us from being able to control for potential differences in eye gaze position.

Conclusions

These methods confirmed pronounced neural signatures that differentiate brain responses to biological and scrambled motion. Our sample of undiagnosed females enriched for family genetic loading enabled discovery of numerous contrasts between carriers and non-carriers of risk of ASD that may index variations in visual attention and motion processing related to genetic susceptibility and inform our understanding of mechanisms incurred by inherited liability for ASD.