bluuebunny/crossref_metadata_2025 huggingface dataset:
The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway
Authors: Zhu Linwen , Li Zhe , Yu Xiuchong , Ruan Yao , Shen Yijing , Shao Yongfu , Zhang Xinjun , Ye Guoliang , Guo Junming
Published: July 2021

Background

Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer.

Methods

Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice.

Results

tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth.

Conclusions

tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.
miR-20a-5p contributes to osteogenic differentiation of human dental pulp stem cells by regulating BAMBI and activating the phosphorylation of Smad5 and p38
Authors: Cen Xiao , Pan Xuefeng , Zhang Bo , Huang Wei , Pei Fang , Luo Tao , Huang Xinqi , Liu Jun , Zhao Zhihe
Published: July 2021

Background

Human dental pulp stem cells (hDPSCs) are the preferable choice of seed cells for craniomaxillofacial bone tissue regeneration. As a member of the miR-17-92 cluster, miR-20a-5p functions as an important regulator during bone remodeling. This study aimed to investigate the roles and mechanisms of miR-20a-5p during osteogenesis of hDPSCs.

Methods

Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to determine the expression of miR-20a-5p during osteogenesis of hDPSCs. We interfered with the expression of miR-20a-5p in hDPSCs to clarify the function of miR-20a-5p on osteogenesis both in vitro and vivo. Direct bind sites between miR-20a-5p and BAMBI were confirmed by dual-luciferase reporter assay, and the underlying mechanisms were investigated with cell co-transfections.

Results

The expression of miR-20a-5p was showed to be upregulated during osteogenesis of hDPSCs. Inhibition of miR-20a-5p could weaken the intensity of ALP/ARS staining and downregulate the expression of mRNAs and proteins of osteogenic markers, while overexpression of miR-20a-5p could enhance the intensity of ALP/ARS staining and the expression of osteogenic markers. Both micro-CT reconstruction images and histological results showed that miR-20a-5p could promote the regeneration of calvarial defects. miR-20a-5p directly targeted bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), and the latter one was an inhibitor of hDPSC osteogenesis. Silencing BAMBI partially reversed the suppression effect of miR-20a-5p knockdown on osteogenesis. Phosphorylation of Smad5 and p38 was decreased when miR-20a-5p was silenced, whereas p-Smad5 and p-p38 were upregulated when miR-20a-5p was overexpressed or BAMBI was silenced.

Conclusions

It is demonstrated that miR-20a-5p functioned as a regulator of BAMBI to activate the phosphorylation of Smad5 and p38 during osteogenic differentiation of hDPSCs.
Risk factors for norovirus infection in healthcare workers during nosocomial outbreaks: a cross-sectional study
Authors: Torén Kjell , Schiöler Linus , Nenonen Nancy P. , Hannoun Charles , Roth Anette , Andersson Lars-Magnus , Westin Johan , Bergström Tomas
Published: July 2021

Background

Norovirus outbreaks cause severe medico-socio-economic problems affecting healthcare workers and patients. The aim of the study was to investigate prevalence of norovirus infection and risk factors for infection in healthcare workers during nosocomial outbreaks.

Methods

A cross-sectional study of norovirus infections in healthcare workers was performed in seven outbreak wards in a large university hospital. Packs (swab for rectal sampling, and questionnaire) were posted to healthcare workers on notification of a ward outbreak. Rectal samples were examined with norovirus-specific real-time PCR. Replies from questionnaires were analysed using logistic regression models with norovirus genogroup (G)II positive findings as dependent variable. The results are expressed as odds ratios (OR) with 95% confidence intervals (CI). Sequencing and phylogenetic analyses (1040 nucleotides) were used to characterize norovirus strains from healthcare workers. Cluster analyses included norovirus GII.4 strains detected in ward patients during the ongoing outbreaks.

Results

Of 308 packs issued to healthcare workers, 129 (42%) were returned. norovirus GII was detected in 26 healthcare workers (20.2%). Work in cohort care (OR 4.8, 95% CI 1.4–16.3), work in wards for patients with dementia (OR 13.2, 95% CI 1.01–170.7), and having diarrhoea, loose stools or other gastrointestinal symptoms the last week (OR 7.7, 95% CI 2.5–27.2) were associated with increased norovirus prevalence in healthcare workers. Sequencing revealed norovirus GII.4 in healthcare workers samples, and strains detected in healthcare workers and ward patients during a given ward outbreak showed ≥ 99% similarity.

Conclusion

Norovirus positive findings in healthcare workers were strongly associated with symptomatic infection, close contact with sick patients, and dementia nursing.
Sequence type 17 is a predictor of subsequent bacteremia in vancomycin-resistant Enterococcus faecium-colonized patients: a retrospective cohort study
Authors: Kim Si-Ho , Cho Sun Young , Kim Hye Mee , Huh Kyungmin , Kang Cheol-In , Peck Kyong Ran , Chung Doo Ryeon
Published: July 2021

Background

Sequence type (ST) 17 vancomycin-resistant Enterococcus faecium (VREF) is frequently isolated in nosocomial settings. The aim of this study was to identify whether ST17 contributes to subsequent bacteremia more often than other STs among hospitalized patients carrying VREF.

Methods

A retrospective cohort study was conducted in patients carrying ST17 VREF and those with non-ST17 VREF. Rectal screening according to hospital policy was used to identify patients with VREF. Subsequent VREF bacteremia events within a year of detection of colonization were recorded. Cox regression analysis was used to adjust the covariates involved in determining the association between ST17 and subsequent bacteremia events.

Results

The cohorts comprised 52 patients with ST17 and 169 patients with non-ST17 VREF. One-year VREF bacteremia-free rates were 85.9% and 90.2%, respectively. In multivariate analysis, ST17 was associated with subsequent bacteremia at an adjusted hazard risk (aHR) of 4.02 (95% confidence interval [CI], 1.32–12.29). Liver transplantation (aHR, 40.08; 95% CI, 4.87–329.76) and hematologic malignancy (aHR, 20.97; 95% CI, 4.87–87.82) were also significant. All cases of subsequent bacteremia in ST17 VREF carriers were caused by ST17; however, subsequent bacteremia in non-ST17 carriers was often caused by ST17 or another ST variant.

Conclusions

A specific genotype, ST17 is a predictor of subsequent bacteremia in hospitalized patients carrying VREF. Patients with a hematologic malignancy and those receiving a liver transplant are also at high risk. More targeted strategies may be needed to prevent VREF infection in hospitals.
Multi-level determinants of failure to receive timely and complete measles vaccinations in Southwest China: a mixed methods study
Authors: Tang Xian-Yan , Cheng Man , Geater Alan , Deng Qiu-Yun , Zhong Ge , Lin Yue-Dong , Chen Ning , Lan Tao , Jiang Long-Yan , Zhu Man-Tong , Li Qiao
Published: July 2021

Background

Measles outbreaks re-emerged in 2013–2014 in Guangxi Zhuang Autonomous Region of China, where measles immunisation coverage is high. The discrepancy between the vaccination coverage and outbreaks indicates that timeliness is crucial, yet there is limited knowledge on the health system barriers to timely vaccination. Using integrated evidence at the household, village clinic, and township hospital levels, this study aimed to identify the determinants of failure in receiving timely measles vaccinations among children in rural Guangxi.

Methods

A multi-stage stratified cluster sampling survey with a nested qualitative study was conducted among children aged 18–54 months in Longan, Zhaoping, Wuxuan, and Longlin counties of Guangxi from June to August 2015. The status of timely vaccinations for the first dose of measles-containing vaccine (MCV1) and the second dose of measles-containing vaccine (MCV2) was verified via vaccination certificates. Data on household-level factors were collected using structured questionnaires, whereas data on village and township-level factors were obtained through in-depth interviews and focus group discussions. Determinants of untimely measles vaccinations were identified using multilevel logistic regression models.

Results

A total of 1216 target children at the household level, 120 villages, and 20 township hospitals were sampled. Children were more likely to have untimely vaccination when their primary guardian had poor vaccination knowledge [MCV1, odds ratio (OR) = 1.72; MCV2, OR = 1.51], had weak confidence in vaccines (MCV1, OR = 1.28–4.58; MCV2, OR = 1.42–3.12), had few practices towards vaccination (MCV1, OR = 12.5; MCV2, OR = 3.70), or had low satisfaction with vaccination service (MCV1, OR = 2.04; MCV2, OR = 2.08). This trend was also observed in children whose village doctor was not involved in routine vaccination service (MCV1, OR = 1.85; MCV2, OR = 2.11) or whose township hospital did not provide vaccination notices (MCV1, OR = 1.64; MCV2, OR = 2.05), vaccination appointment services (MCV1, OR = 2.96; MCV2, OR = 2.74), sufficient and uniformly distributed sessions for routine vaccination (MCV1, OR = 1.28; MCV2, OR = 1.17; MCV1, OR = 2.08), or vaccination service on local market days (MCV1, OR = 2.48).

Conclusions

Guardians with poor knowledge, weak beliefs, and little practice towards vaccination; non-involvement of village doctors in routine vaccinations; and inconvenient vaccination services in township hospitals may affect timely measles vaccinations among children in rural China.

Graphical abstract
Supportive and demanding managerial circumstances and associations with excellent workability: a cross-sectional study of Swedish school principals
Authors: Persson Roger , Leo Ulf , Arvidsson Inger , Nilsson Kerstin , Österberg Kai , Håkansson Carita
Published: July 2021

Background

The leadership of principals is important for school, teacher and student related outcomes. To be capable of doing their work (i.e., having sufficient workability), school principals need proper organisational preconditions, motivation, and good health. It is therefore concerning that some studies suggest that principals have a work situation that risks taxing their health and reducing their workability. However, few studies have examined the psychosocial working conditions of principals and no study has gauged principals’ workability. Accordingly, we decided to examine Swedish principals’ workability and their perceptions of eight demanding and five supportive managerial circumstances as well as the associations between managerial circumstances and reports of excellent workability.

Methods

The participants comprised 2219 Swedish principals (78% women) who completed a cross-sectional web survey in 2018. A brief version of the Gothenburg Manager Stress Inventory (GMSI-Mini) gauged managerial circumstances. Workability was assessed with the workability score (0–10; WAS). Unadjusted and adjusted logistic regression analyses were used to examine associations between managerial circumstances and reports of excellent workability (WAS ≥ 9). Covariates were: length of work experience as a principal, school level, self-rated health, and general self-efficacy.

Results

The results showed that circa 30% of the principals reported excellent workability. The GMSI-Mini results showed that role conflicts, resource deficits, and having to harbour co-workers’ frustrations were the most frequently encountered managerial demands. Meanwhile, cooperating co-workers, supportive manager colleagues, and a supportive private life were the most supportive managerial circumstances. Adjusted logistic regression analyses showed that role conflicts and role demands were associated with an increased likelihood of reporting less than excellent workability. In contrast, supportive managerial colleagues, a supportive private life and supportive organisational structures were associated with an increased likelihood of reporting excellent workability.

Conclusion

Circa 30% of the participating principals perceived their workability to be excellent. Reducing role demands, clarifying the principals’ areas of responsibility and accountability in relation to other actors in the governing chain (role conflicts), striving for increased role clarity, and striving to find ways to separate work and private life, seem to be promising intervention areas if increasing principals’ workability is desired.
Antiangiogenic therapy reverses the immunosuppressive breast cancer microenvironment
Authors: Chen Wuzhen , Shen Lesang , Jiang Jingxin , Zhang Leyi , Zhang Zhigang , Pan Jun , Ni Chao , Chen Zhigang
Published: July 2021

Tumor angiogenesis induces local hypoxia and recruits immunosuppressive cells, whereas hypoxia subsequently promotes tumor angiogenesis. Immunotherapy efficacy depends on the accumulation and activity of tumor-infiltrating immune cells (TIICs). Antangiogenic therapy could improve local perfusion, relieve tumor microenvironment (TME) hypoxia, and reverse the immunosuppressive state. Combining antiangiogenic therapy with immunotherapy might represent a promising option for the treatment of breast cancer. This article discusses the immunosuppressive characteristics of the breast cancer TME and outlines the interaction between the tumor vasculature and the immune system. Combining antiangiogenic therapy with immunotherapy could interrupt abnormal tumor vasculature-immunosuppression crosstalk, increase effector immune cell infiltration, improve immunotherapy effectiveness, and reduce the risk of immune-related adverse events. In addition, we summarize the preclinical research and ongoing clinical research related to the combination of antiangiogenic therapy with immunotherapy, discuss the underlying mechanisms, and provide a view for future developments. The combination of antiangiogenic therapy and immunotherapy could be a potential therapeutic strategy for treatment of breast cancer to promote tumor vasculature normalization and increase the efficiency of immunotherapy.
Tree mortality and regeneration of Euphrates poplar riparian forests along the Tarim River, Northwest China
Authors: Keram Ayjamal , Halik Ümüt , Aishan Tayierjiang , Keyimu Maierdang , Jiapaer Kadeliya , Li Guolei
Published: July 2021

Background

Tree mortality and regeneration (seedling and sapling recruitment) are essential components of forest dynamics in arid regions, especially where subjected to serious eco-hydrological problems. In recent decades, the mortality of the Euphrates poplar (Populus euphratica) along the Tarim River in Northwest China has increased. However, few studies have quantified the causes of mortality and regeneration in this azonal riparian forest type.

Methods

The present study describes the annual hydrological response of tree mortality and regeneration in forest gaps. A total of 60 canopy gaps were investigated in six replicate grid plots (50 m × 50 m) and the annual runoff and water consumption data during the period of 1955–2016 were collected from hydrological stations in the middle reaches of the Tarim River. We compared the regeneration density of seedlings and saplings within the canopy gap areas (CGAs), undercanopy areas (UCAs), and uncovered riverbank areas (RBAs) through detailed field investigation.

Results

Our study found that the mortality of young and middle-aged gap makers has increased remarkably over recent decades, particularly since the year 1996. The main results indicated that regional water scarcity was the primary limiting factor for long-term changes in tree mortality, as shown by a significant correlation between the diameter at breast height (DBH) of dead trees and the annual surface water. The average density (or regeneration rate) of seedlings and saplings was highest in the RBAs, intermediate in the CGAs, and lowest in the UCAs. Compared with the UCAs, the CGAs promote tree regeneration to some extent by providing favorable conditions for the survival and growth of seedlings and saplings, which would otherwise be suppressed in the understory. Furthermore, although the density of seedlings and saplings in the CGAs was not as high as in the RBAs, the survival rate was higher in the CGAs than in the RBAs.

Conclusion

Forest canopy gaps in floodplain areas can play a decisive role in the long-term germination and regeneration of plant species. However, as a typical phreatophyte in this hyper-arid region, the ecosystem structure, functions and services of this fragile P. euphratica floodplain forests are threatened by a continuous decrease of water resources, due to excessive water use for agricultural irrigation, which has resulted in a severe reduction of intact poplar forests. Furthermore, the survival of seedlings and saplings is influenced by light availability and soil water at the regional scale. Our findings suggest that policymakers may need to reconsider the restoration and regeneration measures implemented in riparian P. euphratica forests to improve flood water efficiency and create canopy gaps. Our results provide with valuable reference information for the conservation and sustainable development of floodplain forest ecosystems.
Estimating a global demand model for soybean traffic through the Panama Canal
Authors: Ho Javier , Bernal Paul
Published: July 2021

This study attempts to fit a global demand model for soybean traffic through the Panama Canal using Ordinary Least Square. Most of the soybean cargo through the interoceanic waterway is loaded on the U.S. Gulf and East Coast ports -mainly destined to East Asia, especially China-, and represented about 34% of total Panama Canal grain traffic between fiscal years 2010–19. To estimate the global demand model for soybean traffic, we are considering explanatory variables such as effective toll rates through the Panama Canal, U.S. Gulf- Asia and U.S. Pacific Northwest- Asia freight rates, Baltic Dry Index, bunker costs, soybean export inspections from the U.S. Gulf and Pacific Northwest, U.S. Gulf soybean basis levels, Brazil’s soybean exports and average U.S. dollar index. As part of the research, we are pursuing the estimation of the toll rate elasticity of vessels transporting soybeans via the Panama Canal. Data come mostly from several U.S. Department of Agriculture sources, Brazil’s Secretariat of Foreign Trade (SECEX) and from Panama Canal transit information. Finally, after estimation of the global demand model for soybean traffic, we will discuss the implications for future soybean traffic through the waterway, evaluating alternative routes and sources for this trade.
Adult death registration in Matlab, rural Bangladesh: completeness, correlates, and obstacles
Authors: Haider M. Moinuddin , Alam Nurul , Ibn Bashar Mamun , Helleringer Stéphane
Published: July 2021

Civil registration of vital events such as deaths and births is a key part of the process of securing rights and benefits for individuals worldwide. It also enables the production of vital statistics for local planning of social services. In many low- and lower-middle-income countries, however, civil registration and vital statistics (CRVS) systems do not adequately register significant numbers of births and, especially, deaths. In this study, we aim to estimate the completeness of adult death registration (for age 15 and older) in the Matlab health and demographic surveillance system (HDSS) area in Bangladesh and to identify reasons for (not) registering deaths in the national CRVS system. We conducted a sample survey of 2538 households and recorded 571 adult deaths that had occurred in the 3 years preceding the survey. Only 17% of these deaths were registered in the national CRVS system, with large gender differences in registration rates (male = 26% vs. female = 5%). Respondents who reported that a recent death in the household was registered indicated that the primary reasons for registration were to secure an inheritance and to access social services. The main reasons cited for not registering a death were lack of knowledge about CRVS and not perceiving the benefits of death registration. Information campaigns to raise awareness of death registration, as well as stronger incentives to register deaths, may be needed to improve the completeness of death registration in Bangladesh.
Effects of mesh loop modes on performance of unstructured finite volume GPU simulations
Authors: Weng Yue , Zhang Xi , Guo Xiaohu , Zhang Xianwei , Lu Yutong , Liu Yang
Published: July 2021

In unstructured finite volume method, loop on different mesh components such as cells, faces, nodes, etc is used widely for the traversal of data. Mesh loop results in direct or indirect data access that affects data locality significantly. By loop on mesh, many threads accessing the same data lead to data dependence. Both data locality and data dependence play an important part in the performance of GPU simulations. For optimizing a GPU-accelerated unstructured finite volume Computational Fluid Dynamics (CFD) program, the performance of hot spots under different loops on cells, faces, and nodes is evaluated on Nvidia Tesla V100 and K80. Numerical tests under different mesh scales show that the effects of mesh loop modes are different on data locality and data dependence. Specifically, face loop makes the best data locality, so long as access to face data exists in kernels. Cell loop brings the smallest overheads due to non-coalescing data access, when both cell and node data are used in computing without face data. Cell loop owns the best performance in the condition that only indirect access of cell data exists in kernels. Atomic operations reduced the performance of kernels largely in K80, which is not obvious on V100. With the suitable mesh loop mode in all kernels, the overall performance of GPU simulations can be increased by 15%-20%. Finally, the program on a single GPU V100 can achieve maximum 21.7 and average 14.1 speed up compared with 28 MPI tasks on two Intel CPUs Xeon Gold 6132.
SCGB3A1 gene DNA methylation status is associated with breast cancer in Egyptian female patients
Authors: Nomair Azhar Mohamed , Ahmed Sanaa Shawky , Mohammed Ayman Farouk , El Mansy Hazem , Nomeir Hanan Mohamed
Published: July 2021

Background

In recent years, hypermethylation of gene promoters has emerged as one of the fundamental mechanisms for the inactivation of tumor suppressor genes and has a potential role in the early detection of breast cancer. The present study is a case-control study aimed to quantify the methylation levels in the promoters of secretoglobin 3A1 (SCGB3A1), and ataxia-telangiectasia mutated (ATM) genes and evaluate their relation to clinicopathological features of the tumor in a cohort of Egyptian female patients with breast cancer.

Methods

Genomic deoxyribonucleic acid (DNA) was extracted from 100 tissue samples, 50 breast cancer tissues and 50 adjacent non-cancerous breast tissues, then, it was subjected to bisulfite conversion. The converted DNA was amplified by real-time PCR; then, pyrosequencing was performed to quantify DNA methylation levels in four CpG sites in ATM and SCGB3A1 gene promoters. The methylation data were presented as the percentage of average methylation of all the observed CpG sites and were calculated for each sample and each gene.

Results

The percentage of DNA methylation of the SCGB3A1 promoter was significantly higher in the tumor group than in the normal group (P= 0.001). However, a non-statistical significance difference was found in the DNA methylation percentage of the ATM promoter in the tumor group compared to the normal group (P = 0.315). The SCGB3A1 promoter methylation frequency was significantly associated with estrogen receptors (ER) and progesterone receptors (PR) positive tumors, lymph node metastasis, and lymphovascular invasion. However, no association was found between ATM methylation status and the different clinicopathological features of the tumor.

Conclusions

The findings of this work showed that the SCGB3A1 promoter methylation was significantly higher in the tumor group and was significantly associated with different clinicopathologic features in breast cancer. It may be considered as a suitable biomarker for diagnosis and prognosis. However, the promoter methylation levels of the ATM gene in breast cancer cases were unable to distinguish between breast cancer tissues and adjacent normal tissues, and there is no evidence that epigenetic silencing by ATM methylation has a role in breast cancer pathogenesis.
Type X dual left anterior descending (LAD) artery masquerading as type 1 LAD — a case report
Authors: Bhargav Anish , Otaal Parminder S. , Singhal Manphool K.
Published: July 2021

Background

Dual left anterior descending (LAD) coronary artery is a rare congenital anomaly. To date, eleven variants of dual LAD have been described with three published reports of type X dual LAD. Here, we describe a new variant of type X dual LAD with a short LAD artery masquerading as type 1 LAD.

Case presentation

A 42-year hypertensive female presented with recent onset angina with a treadmill test positive for inducible ischemia. Coronary angiography showed a normal right coronary artery (RCA). The left main coronary artery (LMCA) originated from the left sinus of Valsalva (SOV), giving rise to a LAD and the left circumflex artery (LCX). Appearing a normal angiogram with type 1 LAD based on its length, the presence of a large bare area in LAD territory (especially at the apex) and lack of septal branches prompted a search for an additional vessel. Right SOV injection showed a vessel originating separately from RCA, which was confirmed to be a long LAD on selective injection, with a pre-pulmonic course and giving rise to septal branches exclusively before wrapping around the apex. Computed tomography coronary angiography (CTCA) confirmed the pre-pulmonic course of long LAD, defined its entry to the distal interventricular septum to the right of short LAD, and ruled out other coronary artery anomalies. In the absence of a stenotic lesion in the epicardial coronaries, angina in our case was presumed to be due to microvascular dysfunction. She was discharged on beta-blocker therapy for co-existing hypertension and is asymptomatic on follow-up at one year.

Conclusions

A short LAD artery of type X Dual LAD could be potentially misdiagnosed as type 1 LAD based on its length. However, an active search for a long LAD could properly diagnose the case as a variant of type X dual LAD, which has important clinical implications. Its awareness is critical for cardiologists and cardiac surgeons to correctly interpret the coronary angiogram and plan proper management.
Antipsychotic monitoring in dementia: quality of completion of antipsychotic monitoring forms in an older adult mental health service
Authors: Anderson Helen , Kolliakou Anna , Harwood Daniel , Funnell Nicola , Stewart Robert , Bishara Delia
Published: July 2021

Aims and method

To support safe prescribing of antipsychotics in dementia, antipsychotic monitoring forms were embedded into our electronic health records. We present a review of the data collected on these forms to assess prescribing and identify areas for improvement in our practice and processes. Data were extracted from the structured fields of antipsychotic initiation and review forms completed between 1 January 2018 and 31 January 2020.

Results

We identified gaps in practice where improvements could be made, mainly with regard to physical health monitoring (and particularly electrocardiograms, performed in only 50% of patients) and the low (less than 50%) recorded use of non-pharmacological interventions for behavioural and psychological symptoms of dementia. In addition, antipsychotic treatment was continued despite lack of benefit in almost 10% of reviews.

Clinical implications

We advocate for recommendations on physical health monitoring of people with dementia taking antipsychotics to be added to the National Institute for Health and Care Excellence guidance on dementia and the Prescribing Observatory for Mental Health (POMH-UK) national audit.
Adolescent cannabis use, depression and anxiety disorders in the Northern Finland Birth Cohort 1986
Authors: Mustonen Antti , Hielscher Emily , Miettunen Jouko , Denissoff Alexander , Alakokkare Anni-Emilia , Scott James G. , Niemelä Solja
Published: July 2021

Background

Cannabis use has been associated with increased risk of psychiatric disorders. However, associations between adolescent cannabis use, depression and anxiety disorders are inconsistently reported in longitudinal samples.

Aims

To study associations of adolescent cannabis use with depression and anxiety disorders.

Method

We used data from the Northern Finland Birth Cohort 1986, linked to nationwide registers, to study the association between adolescent cannabis use and depression and anxiety disorders until 33 years of age (until 2018).

Results

We included 6325 participants (48.8% male) in the analyses; 352 (5.6%) participants reported cannabis use until 15–16 years of age. By the end of the follow-up, 583 (9.2%) participants were diagnosed with unipolar depression and 688 (10.9%) were diagnosed with anxiety disorder. Cannabis use in adolescence was associated with an increased risk of depression and anxiety disorders in crude models. After adjusting for parental psychiatric disorder, baseline emotional and behavioural problems, demographic factors and other substance use, using cannabis five or more times was associated with increased risk of anxiety disorders (hazard ratio 2.01, 95% CI 1.15–3.82), and using cannabis once (hazard ratio 1.93, 95% CI 1.30–2.87) or two to four times (hazard ratio 2.02, 95% CI 1.24–3.31) was associated with increased risk of depression.

Conclusions

Cannabis use in adolescence was associated with an increased risk of future depression and anxiety disorders. Further research is needed to clarify if this is a causal association, which could then inform public health messages about the use of cannabis in adolescence.
Changes in Burnout Among Oncology Physician Assistants Between 2015 and 2019
Authors: Tetzlaff Eric D. , Hylton Heather M. , Ruth Karen J. , Hasse Zachary , Hall Michael J.
Published: July 2021

PURPOSE:

Burnout has significant implications for the individual provider, the oncology workforce, and the quality of care for patients with cancer. The primary aim of this study was to explore temporal changes in burnout among physician assistants (PAs) in oncology in 2019 compared with 2015.

METHODS:

Oncology PAs were surveyed to assess for burnout using the Maslach Burnout Inventory according to the same cross-sectional design of the study performed in 2015. Comparison between oncology PAs in 2015 and 2019 in the prevalence of burnout and personal and professional characteristics was performed.

RESULTS:

Two hundred thirty-four participants completed the full-length survey. The participants in 2015 and 2019 were similar in age (41.8 v 40.3 years), sex (88.8% v 86.3% female), number of years as a PA in oncology (9.6 v 10), and percentage involved in academic practice (55.2% v 59.2%). There was a significant increase in burnout in 2019 compared with 2015 with 48.7% of PAs reporting at least one symptom of burnout compared with 34.8% (odds ratio for burnout, 2019 v 2015 = 1.92 [95% CI, 1.40 to 2.65], P < 0.001). The odds of burnout remained higher in 2019 compared with 2015 when adjusted for age, sex, relationship status, practice setting, subspecialty, practice type, and hours worked. Factors associated with burnout in both 2015 and 2019 include the percentage of time spent on patient care, collaborative physician relationship, number of hours worked, and satisfaction with compensation. No new factors associated with burnout emerged in 2019 that were not identified in 2015.

CONCLUSION:

The rate of burnout of oncology PAs has significantly increased. Burnout in oncology PAs is multifactorial, and the increase cannot be easily explained. Additional research is needed to better define the drivers of PA burnout.
Differential Activity of PARP Inhibitors inBRCA1- VersusBRCA2-Altered Metastatic Castration-Resistant Prostate Cancer
Authors: Taza Fadi , Holler Albert E. , Fu Wei , Wang Hao , Adra Nabil , Albany Costantine , Ashkar Ryan , Cheng Heather H. , Sokolova Alexandra O. , Agarwal Neeraj , Kessel Adam , Bryce Alan , Nafissi Nellie , Barata Pedro , Sartor A. Oliver , Bastos Diogo , Smaletz Oren , Berchuck Jacob E. , Taplin Mary-Ellen , Aggarwal Rahul , Sternberg Cora N. , Vlachostergios Panagiotis J. , Alva Ajjai S. , Su Christopher , Marshall Catherine H. , Antonarakis Emmanuel S.
Published: July 2021

PURPOSE

Two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and rucaparib) are US Food and Drug Administration–approved for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/ 2 mutations, but the relative efficacy of PARP inhibition in BRCA1- versus BRCA2-altered mCRPC is understudied.

METHODS

We conducted a multicenter retrospective analysis involving 12 sites. We collected genomic and clinical data from 123 patients with BRCA1/ 2-altered mCRPC who were treated with PARP inhibitors. The primary efficacy end point was the prostate-specific antigen (PSA) response (≥ 50% PSA decline) rate. Secondary end points were PSA progression-free survival (PSA-PFS), clinical or radiographic PFS, and overall survival. We compared clinical outcomes, and other genomic characteristics, among BRCA1- versus BRCA2-altered mCRPC.

RESULTS

A total of 123 patients (13 BRCA1 and 110 BRCA2) were included. PARP inhibitors used were olaparib (n = 116), rucaparib (n = 3), talazoparib (n = 2), and veliparib (n = 2). At diagnosis, 72% of patients had Gleason 8-10 disease. BRCA1 patients were more likely to have metastatic disease at presentation (69% v 37%; P = .04). Age, baseline PSA, metastatic distribution, and types of previous systemic therapies were similar between groups. There were equal proportions of germline mutations (51% v 46%; P = .78) in both groups. BRCA1 patients had more monoallelic (56% v 41%; P = .49) and concurrent TP53 (55% v 36%; P = .32) mutations. PSA50responses in BRCA1- versus BRCA2-altered patients were 23% versus 63%, respectively ( P = .01). BRCA2 patients achieved longer PSA-PFS (HR, 1.94; 95% CI, 0.92 to 4.09; P = .08), PFS (HR, 2.08; 95% CI, 0.99 to 4.40; P = .05), and overall survival (HR, 3.01; 95% CI, 1.32 to 6.83; P = .008). Biallelic (compared with monoallelic) mutations, truncating (compared with missense) mutations, and absence of a concurrent TP53 mutation were associated with PARP inhibitor sensitivity.

CONCLUSION

PARP inhibitor efficacy is diminished in BRCA1- versus BRCA2-altered mCRPC. This is not due to an imbalance in germline mutations but might be related to more monoallelic mutations and/or concurrent TP53 alterations in the BRCA1 group.
Remnant Cholesterol and Cardiovascular Mortality in Patients With Type 2 Diabetes and Incident Diabetic Nephropathy
Authors: Yu Dahai , Wang Zheng , Zhang Xiaoxue , Qu Bingjie , Cai Yamei , Ma Shuang , Zhao Zhanzheng , Simmons David
Published: July 2021

Context

The association between remnant cholesterol (remnant-C) and cardiovascular mortality in patients with type 2 diabetes (T2D) and incident diabetic nephropathy remains unclear.

Objective

To examinie the association between remnant-C and cardiovascular mortality in patients with T2D, chronic kidney disease (CKD) stages 3 to 5, and newly diagnosed DN.

Methods

This study determined the baseline lipid profile and searched for deaths with cardiovascular disease (CVD) within 2 years of baseline among 2282 adults enrolled between January 1, 2015 and December 31, 2016, who had T2D, CKD stages 3 to 5, and newly diagnosed DN. Adjusted logistic regression models were used to assess the associations between lipid, especially remnant-C concentration (either as continuous or categorical variables), and risk of cardiovascular mortality.

Results

In multivariable-adjusted analyses, low-density lipoprotein cholesterol (LDL-C) (odds ratio [OR], 1.022; 95% CI, 1.017-1.026, per 10 mg/dL), high-density lipoprotein cholesterol (HDL-C) (OR, 0.929; 95% CI, 0.922-0.936, per 5 mg/dL), non–HDL-C (OR, 1.024; 95% CI, 1.021-1.028, per 10 mg/dL), and remnant-C (OR, 1.115; 95% CI, 1.103-1.127, per 10 mg/dL), but not triglycerides were associated with cardiovascular mortality. Atherogenic dyslipidemia (triglycerides > 150 mg/dL [1.69 mmol/L] and HDL-C < 40 mg/dL in men or < 50 mg/dL in women) was also associated with cardiovascular mortality (OR, 1.073; 95% CI, 1.031-1.116). Remnant-C greater than or equal to 30 mg/dL differentiated patients at a higher risk of cardiovascular mortality from those with lower concentrations, especially with interaction with LDL-C level greater than 100 mg/dL: The highest risk was found in patients with higher levels both of remnant-C and LDL-C (OR, 1.696; 95% CI, 1.613-1.783).

Conclusion

In patients with T2D, CKD stages 3 to 5, and incident DN, remnant-C was associated with a higher risk of death with CVD. Different from the general population, the interaction of remnant-C and LDL-C was associated with the highest risk of cardiovascular mortality.
The quadrupedal walking gait of the olive baboon, Papio anubis: an exploratory study integrating kinematics and EMG
Authors: Druelle François , Supiot Anthony , Meulemans Silke , Schouteden Niels , Molina-Vila Pablo , Rimbaud Brigitte , Aerts Peter , Berillon Gilles
Published: July 2021

Primates exhibit unusual quadrupedal features (e.g. diagonal gaits, compliant walk) compared with other quadrupedal mammals. Their origin and diversification in arboreal habitats have certainly shaped the mechanics of their walking pattern to meet the functional requirements necessary for balance control in unstable and discontinuous environments. In turn, the requirements for mechanical stability probably conflict with mechanical energy exchange. In order to investigate these aspects, we conducted an integrative study on quadrupedal walking in the olive baboon (Papio anubis) at the Primatology station of the CNRS in France. Based on kinematics, we describe the centre of mass mechanics of the normal quadrupedal gait performed on the ground, as well as in different gait and substrate contexts. In addition, we studied the muscular activity of six hindlimb muscles using non-invasive surface probes. Our results show that baboons can rely on an inverted pendulum-like exchange of energy (57% on average, with a maximal observed value of 84%) when walking slowly (<0.9 m s−1) with a tight limb phase (∼55%) on the ground using diagonal sequence gaits. In this context, the muscular activity is similar to that of other quadrupedal mammals, thus reflecting the primary functions of the muscles for limb movement and support. In contrast, walking on a suspended branch generates kinematic and muscular adjustments to ensure better control and to maintain stability. Finally, walking using the lateral sequence gait increases muscular effort and reduces the potential for high recovery rates. The present exploratory study thus supports the assumption that primates are able to make use of an inverted pendulum mechanism on the ground using a diagonal walking gait, yet a different footfall pattern and substrate appear to influence muscular effort and efficiency.
Case series of the first three severe COVID-19 patients treated with the secretome of hypoxia-mesenchymal stem cells in Indonesia
Authors: Putra Agung , Widyatmoko Agus , Ibrahim Sugeng , Amansyah Fajar , Amansyah Farid , Berlian Mukti Arja , Retnaningsih Retnaningsih , Pasongka Zenitalia , Sari Flora Eka , Rachmad Basuki
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the outbreak of coronavirus disease 2019 (COVID-19), which has been rapidly spreading. Several guideline therapies have been proposed as a possible treatment for SARS-CoV-2, however, these therapies are not sufficient to treat a severe condition of SARS-CoV-2 infection characterised by the increase of D-dimer and C-reactive protein (CRP) levels, and patchy ground-glass opacities (GGOs). Secretome-mesenchymal stem cells (S-MSCs) produced by MSCs under hypoxia could excessively release several anti-inflammatory cytokines and growth factors to control the COVID-19 cytokine storm and accelerate lung injury improvement. This is the first study investigating the clinical outcomes of three severe COVID-19 patients admitted to the intensive care unit of three different hospitals in Indonesia treated with S-MSCs. The decrease of D-dimer and CRP level was reported for all patients treated with S-MSCs. This was in line with improvement of pulmonary radiology, blood gas level, and hematologic assessment. In conclusion, these cases suggest that S-MSCs could effectively control D-dimer, CRP level and GGOs of severe COVID-19 patients associated with recovered pulmonary function.
Regulatory landscapes of specific miRNAs are conserved between cell lines and primary tumors
Authors: Zhu Hanwen , Ning Boting
Published: July 2021

Background: MicroRNAs are essential gene expression regulators and play important roles in various biological processes, such as cancer. They have shown great translational promise as either diagnostic biomarkers or therapeutic targets. While the similarities between transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia have been thoroughly studied before, less is known on the microRNA side. This project aims to provide critical biological knowledge on the extent of consensus microRNA expression and regulation between cell line models and primary human tumors. 

Method: First, we examined the similarity of miRNA expression profiles between CCLE cell lines and TCGA tumor samples for each cancer type. Next, we compared the expression of miRNAs associating the hallmarks of cancer pathways. Finally, we constructed miRNA-mRNA regulatory network for each cancer type and evaluated whether the regulatory role of each miRNA is conserved between cell lines and tumor samples.  

Results: Our results indicate that, similar to gene expression, how well cancer cell line microRNA expression would capture the transcriptomic profile of human cancer tissues is greatly affected by the tumor type and purity. The cell-type composition for a cancer type also affects how accurately cancer cell lines could reflect the miRNA expression in tumor tissues. Furthermore, through network analysis, we show that certain microRNAs, not all, regulate the same set of target genes in both the cell line and human cancer tissues. 

Conclusions: Through systematically comparing the miRNA expression profile and the regulatory network, our study highlights the biological differences between cell line and tumor samples and provides resources for future miRNA and cancer studies.
Both partners practicing orgasmic meditation report having a mystical-type experience: results using the Mystical Experience Questionnaire
Authors: Siegel Vivian , Emmert-Aronson Benjamin
Published: July 2021

Background: Practitioners in a variety of spiritual/religious traditions have described “mystical experiences”, defined by a common set of qualities. The “Mystical Experience Questionnaire” (MEQ30) provides a validated and quantitative measure of mystical experience, and has been used successfully to demonstrate that the hallucinogenic substance psilocybin triggers a mystical-type experience. Orgasmic Meditation (OM) is a structured, partnered meditative practice involving manual stimulation of the clitoris.  Although the partners in an OM have different roles (one is stroking, and the other is being stroked), both claim benefit from the practice. The aim of the current study is to use the MEQ30 to assess to what extent participants report mystical experiences during OM, and to what extent that experience is correlated between the partners. 

Methods: In Study 1, 780 participants completed the MEQ30 with a single powerful OM in mind. In Study 2, 56 pairs of participants (both partners) completed the MEQ30 after their next OM. If the respondent had a score ≥60% of the maximum possible score on each of the four subscales of the MEQ30, this was considered a “complete” mystical experience. 

Results: Respondents from Study 1 reported an MEQ total score of 3.35 (SD = 1.08), with 62% of respondents reporting a complete mystical experience.  Respondents from Study 2 reported an MEQ total score of 3.21 (SD = 0.92), with 23% reporting a complete mystical experience. We found strong relationships between MEQ total score and role (i.e., stroker or strokee), interrater agreement within-group index (aWG) = 0.46, and an even stronger relationship between partners and MEQ total score, aWG=0.71. 

Conclusions: These findings suggest that OM can trigger a substantial mystical experience in both partners. Whether the brains of people who OM show similar activity changes to those having other mystical experiences awaits future study.