bluuebunny/crossref_metadata_2025 huggingface dataset:
An unprecedented social solidarity stress test
Authors: Mangan David , Gramano Elena , Kullmann Miriam
Published: July 2020

While much of the emphasis has been on when and how economies may safely re-open due to the coronavirus pandemic, this article studies the undervalued workplace considerations therein. The initial responses of Member States to the pandemic are outlined for the purpose of setting out similarities and distinctions, but also and mostly to foreground an analysis to date of unresolved problems related to work. Important points for continued monitoring are also identified and an overview of some of the employment law considerations in re-opening workplaces are critically assessed. Consequently, teleworking garners particular attention due to its prominent role during the lockdown and its possible growing place in labour law in the near future.
A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome
Authors: Abdalla Mohammed Altigani , Deshmukh Harshal , Atkin Stephen , Sathyapalan Thozhukat
Published: July 2020

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.
Barriers to stopping neuroleptic (antipsychotic) treatment in people with schizophrenia, psychosis or bipolar disorder
Authors: Moncrieff Joanna , Gupta Swapnil , Horowitz Mark Abie
Published: July 2020

Most guidelines recommend long-term, indefinite neuroleptic (or antipsychotic) treatment for people with schizophrenia, recurrent psychosis or bipolar disorder, on the basis that these medications reduce the chance of relapse. However, neuroleptics have significant adverse effects, including sexual dysfunction, emotional blunting, metabolic disturbance and brain shrinkage, and patients often request to stop them. Evidence for the benefits of long-term treatment is also not as robust as generally thought. Short-term randomised trials show higher rates of relapse among those whose neuroleptic treatment is discontinued compared with those on maintenance treatment, but they are confounded by adverse effects associated with the withdrawal of established medication. Some longer-term studies show possible advantages of medication reduction and discontinuation in terms of improved social functioning and recovery. Therefore, there is a good rationale for supporting patients who wish to stop their medication, especially given the patient choice agenda favoured by The National Institute for Clinical Excellence (NICE). The major barrier to stopping antipsychotics is an understandable fear of relapse among patients, their families and clinicians. Institutional structures also prioritise short-term stability over possible long-term improvements. The risk of relapse may be mitigated by more gradual reduction of medication, but further research is needed on this. Psychosocial support for patients during the process of reducing medication may also be useful, particularly to enhance coping skills. Guidelines to summarise evidence on ways to reduce medication would be useful. Many patients want to try and stop neuroleptic medication for good reasons, and psychiatrists can help to make this a realistic option by supporting people to do it as safely as possible, with the best chance of a positive outcome.
Feeling Good and Functioning Well in Mathematics Education: Exploring Students’ Conceptions of Mathematical Well-Being and Values
Authors: Hill Julia L. , Kern Margaret L. , Seah (佘伟忠) Wee Tiong , van Driel Jan
Published: July 2020

Purpose:

The high incidence of mathematics anxiety and disengagement in mathematics points to poor student well-being in many mathematics classrooms. Poor well-being may arise in part from poor alignment between student values and classroom experiences. Yet, what student well-being is and how to support it within specific subjects is poorly understood, and intersection between students’ values and well-being in mathematics education is unclear. This article proposes a seven-dimensional framework of student well-being in mathematics education and examines alignment between well-being and values.

Design/Approach/Methods:

One hundred nineteen eighth-grade Australian students responded to three open-ended questions investigating their conceptions of mathematical well-being (MWB) and what they valued most when learning or doing mathematics. Responses were analyzed using a combined deductive/inductive thematic analysis.

Findings:

Findings supported the MWB framework and confirmed an alignment between students’ values and well-being in mathematics education.

Originality/Value:

Our study provides a framework for conceptualizing student well-being in mathematics education, points to areas that aim to improve student well-being, and highlights congruences and discordances between well-being and values.
Hybrid contractual landscapes of governance: Generation of fragmented regimes of public accountability through urban regeneration
Authors: Taşan-Kok Tuna , Atkinson Rob , Martins Maria Lucia Refinetti
Published: July 2020

In this article we explore the idea of public accountability in the contemporary entrepreneurial governance of cities, which are influenced by market dependency and private sector involvement. We specifically focus on the fragmentation of public accountability through hybrid contractual landscapes of governance, in which the public and private sector actors interactively produce a diversity of instruments to ensure performance in service. This is in sharp contrast to the traditional vague norms and values appealed to by urban planning institutions, to safeguard the public interest. We argue that within these complex contractual governance environments public accountability is produced by public and private sector actors, through highly diverse sets of contractual relations and diverse control instruments that define responsibilities of diverse actors who are involved in a project within a market-dependent planning and policy making environment, which contains context-specific characteristics set by the specific rules of public-private collaboration. These complexities mean public accountability has become fragmented and largely reduced to performance control. Moreover, our understanding of contractual urban governance remains vague and unclear due to very limited empirical studies focusing on the actual technologies of contractual urban development. By deciphering the complex hybrid landscapes of contractual governance, with comparative empirical evidence from The Netherlands, UK and Brazil, we demonstrate how public accountability is assuming a more ‘contractual’ and unpredictable meaning in policy and plan implementation process.
Evaluation of surface roughness in drilling particle-reinforced composites
Authors: Ficici Ferit
Published: July 2020

Aluminum matrix composite materials being used in different sectors including automobile, aerospace, defense, and medical and are currently displacing unreinforced materials with their superior mechanical properties. The metal removal process of drilling is widely used in many structural applications. This study experimentally investigates the drilling characteristics of silicon carbide (SiCp)-reinforced Al 7075 composites produced by stir casting method. Also, two different drill materials with high-speed steel (HSS) and titanium nitride (TiN)-coated HSS carry out in drilling operation. The effect of operational parameters such as cutting speed and feed rate and materials parameters such as weight fraction of reinforcement and cutting tools on the surface roughness of drilled holes were evaluated in the drilling operations. The results of the drilling test indicate that the feed rate and cutting speed have a very strong effect on the surface roughness of matrix alloy and composite materials. The surface roughness ( Ra) values increased with increasing the feed rate and decreased with increasing the cutting speed. Under 0.10 mm/rev and 20 m/min drilling conditions and using HSS drill, surface roughness values for matrix, 5% SiC-, 10% SiC-, and 15% SiC-reinforced composites, were obtained 2.57, 2.59, 2.61, and 2.64 µm, respectively; besides, using TiN-coated HSS drill, surface roughness values were obtained 1.60, 1.63, 1.64, and 1.66 µm, respectively. An increase in the weight fraction of the abrasive SiC particle resulted in a very crucial deterioration quality of the drilled hole. TiN-coated HSS drills better performance exhibits than uncoated HSS drills for all the drilling operations about surface roughness properties. Short chip formations observed both the matrix alloy and the composite materials for two different drills in the drilling operations.
A new method to assess the acute toxicity toward honeybees of the abrasion particles generated from seeds coated with insecticides
Authors: Lentola Andrea , Giorio Chiara , Petrucco Toffolo Edoardo , Girolami Vincenzo , Tapparo Andrea
Published: July 2020

Background

Large amounts of insecticide-containing dusts produced from abrasion of the seed dressing can be released into the atmosphere during sowing operations. Neonicotinoid pesticides, introduced in the 1990s for several crops, are the leading products for seed-coating treatments in many countries. Neonicotinoid containing dusts can be effectively intercepted by bees in flight over the sowing field, inducing lethal acute effects, so that restrictions in the use of the main neonicotinoids have been adopted in the European Union. This led to the consequent introduction of replacement insecticides for seed-coating, i.e. methiocarb and thiacloprid, despite the lack of information on both the toxicity and the exposure scenarios for honeybees.

Results

In this study, a laboratory apparatus was developed in order to quantify the toxicity of the dusts produced from the abrasion of the seed coating. This quantification is based on (i) an airstream transporting coating particles into an exposure chamber; (ii) exposure of bees to reproducible and measurable concentrations of insecticide, and (iii) direct measurement of the exposure dose on single bees. The method allowed us to perform in vivo experiments of honeybee exposure to provide toxicity data in more realistic exposure conditions. In fact, the formulation rather than the active principle alone can be tested, and the exposure is through dusts rather than a solution so that specific absorption behavior can be studied in representative environmental conditions. The method was used to quantify the acute toxicity (LD50) of dusts obtained from the abrasion of corn seeds coated with clothianidin, thiacloprid and methiocarb.

Conclusions

Our results show that, surprisingly, the replacement insecticide methiocarb has a toxicity (LD50 = 421–693 ng/bee) in the same order of magnitude as clothianidin (LD50 = 113–451 ng/bee) through this specific exposure route, while thiacloprid (LD50 = 16.9·103 ng/bee) has a significantly lower acute toxicity. Moreover, dusts containing methiocarb and clothianidin show a significant increase in toxicity when, after exposure, bees are kept under high humidity conditions. This suggests that the method here presented can be used to obtain complementary toxicity data in the risk assessment procedure for the authorization of new seed-coating insecticides or new formulations.
Persistent secondary hyperparathyroidism caused by parathyromatosis and supernumerary parathyroid glands in a patient on haemodialysis
Authors: Yang Jun , Zhang Jun , Liu Ning-hu , Liu Hao , Dong Meng-jie
Published: July 2020

Background

Secondary hyperparathyroidism (SHPT) is a common high-risk factor for mortality in end-stage renal disease, and parathyromatosis and supernumerary parathyroid glands are very rare causes of persistent SHPT. Preoperative diagnosis and removal of all hyperplastic parathyroid glands are challenging. We report a rare case of persistent SHPT due to parathyromatosis and supernumerary parathyroid glands and successful management by multiple imaging modalities.

Case presentation

A 53-year-old Chinese woman on haemodialysis experienced discomfort due to itching and bone pain due to persistent SHPT after parathyroidectomy. The supernumerary parathyroid glands and parathyromatosis were detected by multiple imaging modalities, including99mTc-sestamibi (99mTc-MIBI) scans, ultrasonography and four-dimensional computed tomography (4D-CT) and then excised; pathological confirmation was performed. During follow-up, her serum calcium and parathyroid hormone levels were stable in the appropriate ranges, and no complications arose.

Conclusions

Because of persistent SHPH after parathyroidectomy in patients with haemodialysis, multiple imaging modalities, including99mTc-MIBI scans, 4D-CT and ultrasonography, are helpful for detecting supernumerary parathyroid glands and parathyromatoses. Accurate preoperative localization of this rare lesion is important for management, enabling the removal of all affected parathyroid tissues.
Sex differences in subclinical hypothyroidism and associations with metabolic risk factors: a health examination-based study in mainland China
Authors: Jiang Li , Du Jinman , Wu Weizhu , Fang Jianjiang , Wang Jufang , Ding Jinhua
Published: July 2020

Background

The association between subclinical hypothyroidism (SCH) and metabolic risk factors in the general health examination-based population has been widely explored. However, the results have been inconclusive. Additionally, the sex differences in the prevalence of SCH and the association of SCH with metabolic risk factors remain unknown.

Methods

We conducted this cross-sectional study using data from health examination-based participants between June 2016 and April 2018 in our health examination centre. Sex differences SCH and the association of SCH with metabolic risk factors were explored.

Results

The total prevalence of SCH was 3.40% among the 5319 included participants, and 4.90% among the 2306 female participants, which was much higher than the prevalence of 2.26% among the 3013 male participants (p < 0.05). In males, the difference between participants younger than 60 and aged 60 or older was not significant (p = 0.104); while in females, the difference between participants younger than 40 and participants aged 40 or older was statistically significant (p = 0.023). Multivariate logistic regression analysis demonstrated that age (OR = 0.568, p = 0.004), body-mass index (BMI) (OR = 5.029, p < 0.001) and systolic/diastolic blood pressure (SBP/DBP) (OR = 5.243, p < 0.001) were independent predictors of SCH in females, but no metabolic risk factor was significantly associated with SCH in males. Further analysis revealed that the prevalence was much higher in participants with one or two metabolic risk factors than in those with no above metabolic risk factors regardless of age (p < 0.01).

Conclusions

Our study demonstrates that high BMI and/or high blood pressure are associated with SCH in female participants, and the prevalence of SCH among women with one or two metabolic risk factors ranges from 7.69–14.81%, which indicates that in such a population, serum concentrations of TSH and FT4 may be routinely screened in mainland China. Certainly, prospective, large-scale studies with long follow-up period are still necessary to further verify our results.
Marginal and internal fit of full ceramic crowns milled using CADCAM systems on cadaver full arch scans
Authors: Vág János , Nagy Zsolt , Bocklet Christopher , Kiss Tamás , Nagy Ákos , Simon Botond , Mikolicz Ákos , Renne Walter
Published: July 2020

Background

Chairside systems are becoming more popular for fabricating full-ceramic single restorations, but there is very little knowledge about the effect of the entire workflow process on restoration fit. Therefore, this study aimed to compare the absolute marginal discrepancy (AMD) and the full internal fit (FULL) of all-ceramic crowns made by two chairside systems, Planmeca FIT and CEREC, with detailed and standard mill settings.

Methods

One upper molar was prepared for an all-ceramic crown in human cadaver maxilla. Full-arch scans were made by Emerald or Omnicam four times each. Twenty-four e.max crowns were designed and milled by the Planmill 30s or 40s or CEREC MCXL mills with either detailed or standard settings. The cadaver tooth was extracted, and each crown was fixed on it and scanned by a high-resolution microCT scanner. The AMD and FULL were measured digitally in mesio-distal and bucco-lingual 2D slices. The actual and predicted times of the milling were also registered.

Results

No differences were observed between detailed or standard settings in either system. The AMD was significantly higher with CEREC (132 ± 12 μm) than with either Planmill 30s (71 ± 6.9 μm) or 40s (78 ± 7.7 μm). In standard mode, the FULL was significantly higher with CEREC (224 ± 9.6 μm) than with either Planmill 30s (169 ± 8.1 μm) or 40s (178 ± 8.5 μm). There was no difference between actual and predicted time with the two Planmeca models, but with CEREC, the actual time was significantly higher than the predicted time. The 30s had significantly higher actual and predicted times compared to all other models. Across all models, the average milling time was 7.2 min less in standard mode than in detailed mode.

Conclusions

All fit parameters were in an acceptable range. No differences in fit between Planmeca models suggest no effect of spindle number on accuracy. The detailed setting has no improvement in the marginal or internal fit of the restoration, yet it increases milling time.
Comparative analysis of somatic variant calling on matched FF and FFPE WGS samples
Authors: de Schaetzen van Brienen Louise , Larmuseau Maarten , Van der Eecken Kim , De Ryck Frederic , Robbe Pauline , Schuh Anna , Fostier Jan , Ost Piet , Marchal Kathleen
Published: July 2020

Background

Research grade Fresh Frozen (FF) DNA material is not yet routinely collected in clinical practice. Many hospitals, however, collect and store Formalin Fixed Paraffin Embedded (FFPE) tumor samples. Consequently, the sample size of whole genome cancer cohort studies could be increased tremendously by including FFPE samples, although the presence of artefacts might obfuscate the variant calling. To assess whether FFPE material can be used for cohort studies, we performed an in-depth comparison of somatic SNVs called on matching FF and FFPE Whole Genome Sequence (WGS) samples extracted from the same tumor.

Methods

Four variant callers (i.e. Strelka2, Mutect2, VarScan2 and Shimmer) were used to call somatic variants on matching FF and FFPE WGS samples from a metastatic prostate tumor. Using the variants identified by these callers, we developed a heuristic to maximize the overlap between the FF and its FFPE counterpart in terms of sensitivity and precision. The proposed variant calling approach was then validated on nine matched primary samples. Finally, we assessed what fraction of the discrepancy could be attributed to intra-tumor heterogeneity (ITH), by comparing the overlap in clonal and subclonal somatic variants.

Results

We first compared variants between an FF and an FFPE sample from a metastatic prostate tumor, showing that on average 50% of the calls in the FF are recovered in the FFPE sample, with notable differences between callers. Combining the variants of the different callers using a simple heuristic, increases both the precision and the sensitivity of the variant calling. Validating the heuristic on nine additional matched FF-FFPE samples, resulted in an average F1-score of 0.58 and an outperformance of any of the individual callers. In addition, we could show that part of the discrepancy between the FF and the FFPE samples can be attributed to ITH.

Conclusion

This study illustrates that when using the correct variant calling strategy, the majority of clonal SNVs can be recovered in an FFPE sample with high precision and sensitivity. These results suggest that somatic variants derived from WGS of FFPE material can be used in cohort studies.
Statistical driver genes as a means to uncover missing heritability for age-related macular degeneration
Authors: Waksmunski Andrea R. , Grunin Michelle , Kinzy Tyler G. , Igo Robert P. , Haines Jonathan L. , Cooke Bailey Jessica N.
Published: July 2020

Background

Age-related macular degeneration (AMD) is a progressive retinal disease contributing to blindness worldwide. Multiple estimates for AMD heritability (h2) exist; however, a substantial proportion of h2 is not attributable to known genomic loci. The International AMD Genomics Consortium (IAMDGC) gathered the largest dataset of advanced AMD (ADV) cases and controls available and identified 34 loci containing 52 independent risk variants defining known AMD h2. To better define AMD heterogeneity, we used Pathway Analysis by Randomization Incorporating Structure (PARIS) on the IAMDGC data and identified 8 statistical driver genes (SDGs), including 2 novel SDGs not discovered by the IAMDGC. We chose to further investigate these pathway-based risk genes and determine their contribution to ADV h2, as well as the differential ADV subtype h2.

Methods

We performed genomic-relatedness-based restricted maximum-likelihood (GREML) analyses on ADV, geographic atrophy (GA), and choroidal neovascularization (CNV) subtypes to investigate the h2 of genotyped variants on the full DNA array chip, 34 risk loci (n = 2758 common variants), 52 variants from the IAMDGC 2016 GWAS, and the 8 SDGs, specifically the novel 2 SDGs, PPARA and PLCG2.

Results

Via GREML, full chip h2 was 44.05% for ADV, 46.37% for GA, and 62.03% for CNV. The lead 52 variants’ h2 (ADV: 14.52%, GA: 8.02%, CNV: 13.62%) and 34 loci h2 (ADV: 13.73%, GA: 8.81%, CNV: 12.89%) indicate that known variants contribute ~ 14% to ADV h2. SDG variants account for a small percentage of ADV, GA, and CNV heritability, but estimates based on the combination of SDGs and the 34 known loci are similar to those calculated for known loci alone. We identified modest epistatic interactions among variants in the 2 SDGs and the 52 IAMDGC variants, including modest interactions between variants in PPARA and PLCG2.

Conclusions

Pathway analyses, which leverage biological relationships among genes in a pathway, may be useful in identifying additional loci that contribute to the heritability of complex disorders in a non-additive manner. Heritability analyses of these loci, especially amongst disease subtypes, may provide clues to the importance of specific genes to the genetic architecture of AMD.
A rare Down syndrome foetus with de novo 21q;21q rearrangements causing false negative results in non-invasive prenatal testing: a case report
Authors: Xu Hui-Hui , Dai Mei-Zhen , Wang Kai , Zhang Yang , Pan Fei-Yan , Shi Wei-Wu
Published: July 2020

Background

Non-invasive prenatal testing (NIPT) has been established as a routine prenatal screening to assess the risk of common foetal aneuploidy disorder (trisomy 21, 18, and 13). NIPT has high sensitivity and high specificity, but false positive and false negative results still exist. False negative NIPT results involving Down syndrome are rare, but have a high clinical impact on families and society.

Case presentation

We described a case of a foetus that tested “negative” for trisomy 21 (Z-score was 0.664) by NIPT based on the semiconductor sequencing platform (SSP). The foetal fraction of cell-free DNA was 16.9%; this percentage was much larger than the threshold of 4% for obtaining accurate NIPT results. However, postnatally, the newborn was diagnosed with Down syndrome with the 46,XY,der(21;21)(q10;q10),+ 21 karyotype.

Conclusions

We presented a case of false negative NIPT results, which may occur through biological mechanisms rather than poor quality, technical errors or negligence. It is imperative for clinical geneticists and their patients to understand that NIPT is still a screening test.
A methylation‐based mRNA signature predicts survival in patients with gastric cancer
Authors: Li Yang , Sun Rongrong , Zhang Youwei , Yuan Yuan , Miao Yufeng
Published: July 2020

Background

Evidence suggests that altered DNA methylation plays a causative role in the occurrence, progression and prognosis of gastric cancer (GC). Thus, methylated-differentially expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in GC.

Methods

Four genomics profiling datasets were used to identify MDEGs. Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis were used to explore the biological roles of MDEGs in GC. Univariate Cox and LASSO analysis were used to identify survival-related MDEGs and to construct a MDEGs-based signature. The prognostic performance was evaluated in two independent cohorts.

Results

We identified a total of 255 MDEGs, including 192 hypermethylation-low expression and 63 Hypomethylation-high expression genes. The univariate Cox regression analysis showed that 83 MDEGs were associated with overall survival. Further we constructed an eight-MDEGs signature that was independent predictive of prognosis in the training cohort. By applying the eight-MDEGs signature, patients in the training cohort could be categorized into high-risk or low-risk subgroup with significantly different overall survival (HR = 2.62, 95% CI 1.71–4.02, P < 0.0001). The prognostic value of the eight-MDEGs signature was confirmed in another independent GEO cohort (HR = 1.35, 95% CI 1.03–1.78, P = 0.0302) and TCGA-GC cohort (HR = 1.85, 95% CI 1.16–2.94, P = 0.0084). Multivariate cox regression analysis proved the eight-MDEGs signature was an independent prognostic factor for GC.

Conclusion

We have thus established an innovative eight-MDEGs signature that is predictive of overall survival and could be a potentially useful guide for personalized treatment of GC patients.
RETRACTED ARTICLE: CircRNA hsa_circRNA_0000069 promotes the proliferation, migration and invasion of cervical cancer through miR-873-5p/TUSC3 axis
Authors: Zhang Shuaisai , Chen Zhengli , Sun Jinxue , An Na , Xi Qinghua
Published: July 2020

Background

Cervical cancer (CC) is the second leading cause of cancer deaths in women worldwide, still lacking effective biomarkers and therapies for diagnosis and treatment. CircRNAs are a class of endogenous RNAs that regulate gene expression through interacting with miRNAs, implicating in the progression of cancers. Yet the roles of circRNAs in CC are not fully characterized.

Methods

Fifty pairs of tumor and adjacent normal tissues from CC patients, as well as four CC cell lines and a normal human cervical epithelial cell line were subjected to qRT-PCR assay to assess the mRNA levels of hsa_circ_0000069. CCK-8 and colony formation assays were conducted to detect the proliferation of CC cells. Transwell assay was used to evaluate the migration and invasion capabilities of CC cells. RNA pull-down and luciferase assays were used to determine the interaction between hsa_circ_0000069 and miR-873-5p. A xenograft model of CC was established to verify the in vivo function of hsa_circ_0000069 in CC progression.

Results

We firstly demonstrated that hsa_circ_0000069 was significantly upregulated and closely related to the lymph node metastasis, and poor prognosis of CC patients. Besides, hsa_circ_0000069 promoted CC cell proliferation, migration, and invasion. The knockdown of hsa_circ_0000069 also inhibited CC tumor growth in vivo. Mechanically, we revealed that hsa_circ_0000069 functioned as an oncogene in CC, which is the sponge of miR-873-5p to facilitate the TUSC3 expression, consequently promoting CC progression.

Conclusion

We demonstrated a critical hsa_circ_0000069-miR-873-5p-TUSC3 function network involved in the CC progression, which provides mechanistic insights into the roles of CircRNAs in CC progression and a promising therapeutic target for CC treatment.
RNF181 modulates Hippo signaling and triple negative breast cancer progression
Authors: Zhou Rui , Ding Yinlu , Xue Min , Xiong Bin , Zhuang Ting
Published: July 2020

Background

Breast cancer ranks No. 1 in women cancer incidence, while triple negative breast cancer (TNBC) is the most aggressive and the worst prognostic subtype in all breast cancer subtypes. Compared with estrogen receptor alpha positive breast cancer, which could be well controlled by endocrine therapy, TNBC is lack of mature molecular targets for medical therapy. Thus, it is urgent and necessary to discovery the carcinogenic mechanism and potential therapeutic targets for TNBC. Recent studies reveal that Hippo/YAP signaling is an important mediator for TNBC progression. Our current study investigates the role of RING finger protein RNF181 in modulation Hippo/YAP signaling.

Methods

YAP and RN181 protein level were measured by western blot, while the Hippo classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, the trans-well and wound healing were used to measure the cell migration and invasion capacity. Protein stability and ubiquitin assay were used to detect the YAP protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of YAP and RNF181, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of YAP.

Results

Our current study identified a novel modulator-RNF181 as a positive mediator for Hippo/YAP signaling activation in TNBC. RNF181 depletion significantly inhibited TNBC cell migration, invasion and proliferation, which effect could be rescued by YAP overexpression. RNF181 depletion decreased YAP protein level and Hippo signaling target genes, such as CTGF and CYR61, in TNBC cell lines. Immuno-precipitation assay showed that RNF181 interact with YAP and promoted YAP stability by inhibition K48-linked poly-ubiquitination of YAP in TNBC cells. Besides, public available data showed that RNF181 is elevated in breast cancer and related to poor prognosis in TNBC patients.

Conclusion

Our study provides evidence to establish a non-proteolytic mechanism in modulating Hippo signaling in breast cancer. RNF181 could be an interesting marker for triple negative breast cancer prognostics and therapeutics.
Digging for care-seeking behaviour among gold miners in the Guyana hinterland: a qualitative doer non-doer analysis of social and behavioural motivations for malaria testing and treatment
Authors: Yan Shirley D. , Orkis Jennifer , Khan Sohail Saifra , Wilson Sean , Davis TrishAnn , Storey J. Douglas
Published: July 2020

Background

Although Guyana has made significant progress toward malaria control, limited access to malaria testing and treatment services threatens those gains. Mining activities create breeding environments for mosquitoes, and the migrant and mobile mining populations are hard to reach with information and services. The Ministry of Public Health (MoPH) has trained volunteers to test and treat malaria cases in remote regions. However, it remains unclear how miners perceive these testers, the services they provide, or what their malaria care-seeking behaviour is in general. To better address these challenges, Breakthrough ACTION Guyana and MoPH conducted qualitative research from October to November 2018 in Regions 7 and 8 in Guyana.

Methods

A total of 109 individuals, 70 miners, 17 other mining camp staff, and 22 other key stakeholders (e.g. community health workers, pharmacists, and regional leadership), participated in semi-structured interviews and focus group discussions. Results were derived using a framework analysis, with an adjusted doer and non-doer analysis, and organized using the integrated behaviour framework.

Results

Miners sought MoPH-approved services because of close geographic proximity to testing services, a preference for public service treatment, and a desire to correctly diagnose and cure malaria rather than just treat its symptoms. Those who chose to initiate self-treatment—using unregulated medications from the private and informal sector—did so out of convenience and the belief that self-treatment had worked before. Miners who completed the full MoPH-approved treatment understood the need to complete the treatment, while those who prematurely stopped treatment did so because of medication side effects and a desire to feel better as soon as possible.

Conclusion

Reasons why miners do and do not pursue malaria testing and treatment services are diverse. These results can inform better MoPH programming and new solutions to improve malaria outcomes in Guyana.
Race, socioeconomic deprivation, and hospitalization for COVID-19 in English participants of a national biobank
Authors: Patel Aniruddh P. , Paranjpe Manish D. , Kathiresan Nina P. , Rivas Manuel A. , Khera Amit V.
Published: July 2020

Preliminary reports suggest that the Coronavirus Disease 2019 (COVID− 19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. We investigate the racial and socioeconomic associations of COVID− 19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both Black participants (odds ratio 3.7; 95%CI 2.5–5.3) and Asian participants (odds ratio 2.2; 95%CI 1.5–3.2) were at substantially increased risk as compared to White participants. We further observed a striking gradient in COVID− 19 hospitalization rates according to the Townsend Deprivation Index − a composite measure of socioeconomic deprivation − and household income. Adjusting for socioeconomic factors and cardiorespiratory comorbidities led to only modest attenuation of the increased risk in Black participants, adjusted odds ratio 2.4 (95%CI 1.5–3.7). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-White individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.
The association of dietary patterns with endocannabinoids levels in overweight and obese women
Authors: Yagin Neda Lotfi , Hajjarzadeh Samaneh , Aliasgharzadeh Soghra , Aliasgari Fereshteh , Mahdavi Reza
Published: July 2020

Background

Higher levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), the main arachidonic acid-derived endocannabinoids, are frequently reported in overweight and obese individuals. Recently, endocannabinoids have become a research interest in obesity area regarding their role in food intake. The relationship between dietary patterns and endocannabinoids is poorly understood; therefore, this study evaluated the association of the dietary patterns with AEA and 2-AG levels in overweight and obese women.

Methods

In this cross sectional study, 183 overweight and obese females from Tabriz, Iran who aged between 19 and 50 years old and with mean BMI = 32.44 ± 3.79 kg/m2 were interviewed. The AEA and 2-AG levels were measured, and the dietary patterns were assessed using food frequency questionnaire. To extract the dietary patterns, factor analysis was applied. The association between AEA and 2-AG levels and dietary patterns was analyzed by linear regression.

Results

Three major dietary patterns including “Western”, “healthy”, and “traditional” were extracted. After adjusting for age, physical activity, BMI, waist circumference, and fat mass, higher levels of AEA and 2-AG were observed in participants who were in the highest quintile of the Western pattern (P <  0.05). Also, in both unadjusted and adjusted models, significantly lower levels of AEA and 2-AG were detected in the women of the highest quintile of the healthy pattern (P <  0.01). Moreover, there was no significant association between “traditional” pattern and AEA and 2- AG levels in both unadjusted and adjusted models (P > 0.05).

Conclusion

In regard with the lower levels of endocannabinoids in healthy dietary pattern, adherence to healthy pattern might have promising results in regulating endocannabinoids levels.
Effects of sedative-hypnotics on sleep quality among patients with insomnia: evidence from an observational, pre-post study in India
Authors: Satheesh Gautam , Puthean Sandra , Sharma Abhishek , Mishra Shiva Raj , Jose Jeswin , Kakkan Sushil , Unnikrishnan M. K.
Published: July 2020

Background

Insomnia continues to be neglected globally, despite its high prevalence. Guidelines by the health regulatory agencies call for studies to evaluate the effect of sedative-hypnotics on sleep quality.

Methods

We conducted a pre-post observational study to evaluate sleep quality among 186 inpatients receiving short-term oral sedative-hypnotic therapy in a tertiary care teaching hospital in Kozhikode (Kerala), India. Using Pittsburgh Sleep Quality Index_Past-Week (PSQI_PW) questionnaire, patients were interviewed upon hospital admission and at follow up after ≥1-week of sedative-hypnotic therapy. Additionally, we interviewed 36 physicians to understand the current clinical perception about sedative-hypnotics.

Results

Mean (SD) age of the study patients was 59 (7.5) years. Majority (63.4%) of the patients were men. Of the various primary diagnoses for hospitalization, cardiovascular disease was the most common (22.6%, n = 49). Sedative-hypnotic therapy improved the mean (SD) PSQI_PW overall score by 6.79 points (pre: 12.70 (3.5) vs. post: 5.91 (2.8); p < 0.0001). Statistically significant improvements in sleep duration, latency, efficacy, and day dysfunction were observed. Higher proportion of study patients were prescribed benzodiazepines (73.7%) compared to zolpidem (26.3%). Patients treated with zolpidem reported higher improvements in mean overall PSQI_PW scores compared to those treated with benzodiazepines, however these differences were not statistically significant upon adjusting for age, gender and primary diagnosis for hospitalization. Qualitative interviews indicate that that physicians consider zolpidem to be safer and more efficacious.

Conclusions

In our study, sedative-hypnotic therapy helped improve sleep quality among the hospitalized patients. More studies evaluating the comparative efficacy and safety of zolpidem vs. benzodiazepines – including among patient groups with varying demographic and clinical characteristics – are needed. India must develop evidence-based treatment guidelines to inform the clinical practice around the use of sedative-hypnotics.
Rapid exacerbation featuring acute leukemoid reaction after retrolaparoscopic nephrectomy: a rare case report of renal cell carcinoma with postoperative comprehensive genomic profiling
Authors: Zhang Xuhui , Yan Lijuan , Yuan Xiaobin , Bai Tao , Zhang Lei , Han Shuaihong
Published: July 2020

Background

Rapid lethal exacerbation and recurrence featuring acute leukemoid reaction (ALR) after retrolaparoscopic radical nephrectomy (RN) is a relatively rare clinical incident. Performing the reoperation for the patient and analyzing the tissue-based genetic mutation information postoperatively are a skill-demanding and meaningful task, which have been even more rarely reported.

Case presentation

We present a case with a large right renal mass (13.0 × 10.0 × 8.0 cm). This 71-year-old male patient underwent the retrolaparoscopic RN in our department. The operation was technically precise and successful with final pathological diagnosis of hybrid (clear cell and papillary type) renal cell carcinoma (RCC). However, 10 days after the patient was discharged, he was readmitted with the chief complaint of high fever with severe right flank pain. CT scanning revealed that right retroperitoneal hematoma and the blood routine showed the dramatic elevation of white blood cell count (WBC). Even though the immediate broad-spectrum antibiotics were administered without delay and subsequent percutaneous puncturing and drainage was performed, the patient’s condition still exacerbated rapidly. In spite of the reoperation of hematoma evacuation, the patient died of multiple organ failure 10 days after the reoperation. The pathological result of reoperation showed the necrotic and hematoma tissue blended with RCC tumor cells (nuclear grading III), and both of the postoperative tissue-originated comprehensive genomic profiling by using the specimens from the RN and reoperation respectively indicated significant mutations of some oncogenes which might have potential relevance with ALR. Besides, both of the immunohistochemical (IHC) staining results from primary surgical renal mass and reoperative resected tissue revealed the positive expressions of granulocyte colony-stimulating factor (G-CSF).

Conclusions

ALR may be a predictor of poor prognosis in patients with RCC, and comprehensive genomic profiling as well as the alterative expression of G-CSF can help to provide potential valuable genetic etiological information and evidence for guiding the potential effective molecular-targeting therapy.
Can we walk away from cardiovascular disease risk or do we have to ‘huff and puff’? A cross-sectional compositional accelerometer data analysis among adults and older adults in the Copenhagen City Heart Study
Authors: Johansson Melker Staffan , Søgaard Karen , Prescott Eva , Marott Jacob Louis , Schnohr Peter , Holtermann Andreas , Korshøj Mette
Published: July 2020

Background

It is unclear whether walking can decrease cardiovascular disease (CVD) risk or if high intensity physical activity (HIPA) is needed, and whether the association is modified by age. We investigated how sedentary behaviour, walking, and HIPA, were associated with systolic blood pressure (SBP), waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) among adults and older adults in a general population sample using compositional data analysis. Specifically, the measure of association was quantified by reallocating time between sedentary behaviour and 1) walking, and 2) HIPA.

Methods

Cross-sectional data from the fifth examination of the Copenhagen City Heart Study was used. Using the software Acti4, we estimated daily time spent in physical behaviours from accelerometer data worn 24 h/day for 7 days (i.e., right frontal thigh and iliac crest; median wear time: 6 days, 23.8 h/day). SBP, WC, and LDL-C were measured during a physical examination. Inclusion criteria were ≥ 5 days with ≥16 h of accelerometer recordings per day, and no use of antihypertensives, diuretics or cholesterol lowering medicine. The 24-h physical behaviour composition consisted of sedentary behaviour, standing, moving, walking, HIPA (i.e., sum of climbing stairs, running, cycling, and rowing), and time in bed. We used fitted values from linear regression models to predict the difference in outcome given the investigated time reallocations relative to the group-specific mean composition.

Results

Among 1053 eligible participants, we found an interaction between the physical behaviour composition and age. Age-stratified analyses (i.e., </≥65 years; 773 adults, 280 older adults) indicated that less sedentary behaviour and more walking was associated with lower SBP among older adults only. For less sedentary behaviour and more HIPA, the resultsi)indicated an association with a lower SBP irrespective of age,ii)showed an association with a smaller WC among adults, andiii)showed an association with a lower LDL-C in both age groups.

Conclusions

Less sedentary behaviour and more walking seems to be associated with lower CVD risk among older adults, while HIPA types are associated with lower risk among adults. Therefore, to reduce CVD risk, the modifying effect of age should be considered in future physical activity-promoting initiatives.
JC Polyomavirus, progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome: a review
Authors: Harypursat Vijay , Zhou Yihong , Tang Shengquan , Chen Yaokai
Published: July 2020

The human neurotropic virus JC Polyomavirus, a member of the Polyomaviridae family, is the opportunistic infectious agent causing progressive multifocal leukoencephalopathy, typically in immunocompromised individuals. The spectrum of underlying reasons for the systemic immunosuppression that permits JCV infection in the central nervous system has evolved over the past 2 decades, and therapeutic immunosuppression arousing JCV infection in the brain has become increasingly prominent as a trigger for PML. Effective immune restoration subsequent to human immunodeficiency virus-related suppression is now recognized as a cause for unexpected deterioration of symptoms in patients with PML, secondary to a rebound inflammatory phenomenon called immune reconstitution inflammatory syndrome, resulting in significantly increased morbidity and mortality in a disease already infamous for its lethality. This review addresses current knowledge regarding JC Polyomavirus, progressive multifocal leukoencephalopathy, progressive multifocal leukoencephalopathy-related immune reconstitution inflammatory syndrome, and the immunocompromised states that incite JC Polyomavirus central nervous system infection, and discusses prospects for the future management of these conditions.