bluuebunny/crossref_metadata_2025 huggingface dataset:
Parity of esteem and systems thinking: a theory informed qualitative inductive thematic analysis
Authors: Owens Janine , Lovell Karina , Brown Abigail , Bee Penny
Published: October 2022

Background

Parity of Esteem (PoE) is about equality between mental and physical health but is a term lacking definition and clarity. The complexity of the field of mental health and the conversations around PoE add to its opacity. Therefore, the aim of this study is to use systems thinking to explore the strengths and challenges of using PoE.

Methods

This is a secondary analysis of descriptive qualitative data, from 27 qualitative interviews, utilising the World Health Organisation (WHO) system domains as a framework for the inductive thematic analysis.

Results

Examining the current strengths and challenges of systems in mental and physical healthcare using the WHO domains and macro, meso and micro levels, identifies specific actions to redress inequity between mental and physical health provision.

Conclusion

The evidence suggests that moving PoE from rhetoric towards reality requires new configurations with a systems orientation, which uses macro, meso and micro levels to analyse and understand the complexity of relations within and between domain levels and reorienting funding, training and measurement. This requires embedding new competencies, infrastructures and practices within an effective learning healthcare system.
Birth registration coverage according to the sex of the head of household: an analysis of national surveys from 93 low- and middle-income countries
Authors: Wendt Andrea , Hellwig Franciele , Saad Ghada E , Faye Cheikh , Boerma Ties , Barros Aluisio J D , Victora Cesar G
Published: October 2022

Background

Within-country inequalities in birth registration coverage (BRC) have been documented according to wealth, place of residence and other household characteristics. We investigated whether sex of the head of household was associated with BRC.

Methods

Using data from nationally-representative surveys (Demographic and Health Survey or Multiple Indicator Cluster Survey) from 93 low and middle-income countries (LMICs) carried out in 2010 or later, we developed a typology including three main types of households: male-headed (MHH) and female-led with or without an adult male resident. Using Poisson regression, we compared BRC for children aged less than 12 months living the three types of households within each country, and then pooled results for all countries. Analyses were also adjusted for household wealth quintiles, maternal education and urban-rural residence.

Results

BRC ranged from 2.2% Ethiopia to 100% in Thailand (median 79%) while the proportion of MHH ranged from 52.1% in Ukraine to 98.3% in Afghanistan (median 72.9%). In most countries the proportion of poor families was highest in FHH (no male) and lowest in FHH (any male), with MHH occupying an intermediate position. Of the 93 countries, in the adjusted analyses, FHH (no male) had significantly higher BRC than MHH in 13 countries, while in eight countries the opposite trend was observed. The pooled analyses showed t BRC ratios of 1.01 (95% CI: 1.00; 1.01) for FHH (any male) relative to MHH, and also 1.01 (95% CI: 1.00; 1.01) for FHH (no male) relative to MHH. These analyses also showed a high degree of heterogeneity among countries.

Conclusion

Sex of the head of household was not consistently associated with BRC in the pooled analyses but noteworthy differences in different directions were found in specific countries. Formal and informal benefits to FHH (no male), as well as women’s ability to allocate household resources to their children in FHH, may explain why this vulnerable group has managed to offset a potential disadvantage to their children.
Impact of the Food and Drug Administration enforcement policy on flavored e-cigarettes on the online popularity of disposable e-cigarettes: analyses of Google search query data
Authors: Boakye Ellen , Dzaye Omar , Erhabor John , Osuji Ngozi , Obisesan Olufunmilayo , Osei Albert D. , Bhatnagar Aruni , Robertson Rose Marie , Blaha Michael J.
Published: October 2022

Background

The impact of the U.S. Food and Drug Administration's (FDA) initial enforcement policy on flavored cartridge-based e-cigarettes and subsequent notice for the removal of flavored disposable electronic cigarettes (e-cigarettes) such as Puff Bar from the market has not been well evaluated. We, therefore, sought to examine the impact of the e-cigarette flavor-related policy changes on the online popularity of Puff Bar, a prototypic disposable e-cigarette.

Methods

We tabulated the total weekly Google search queries originating from the U.S. for "Puff Bar" and "Puff Bars" from January 1, 2019, to December 31, 2021. We divided the three years into four (4) distinct periods using the dates of the initial announcement to ban non-tobacco flavored e-cigarettes (September 11, 2019), the finalization of the FDA enforcement policy on cartridge-based flavors (January 2, 2020), and the notice for the market withdrawal of flavored disposable e-cigarettes (July 20, 2020) as reference time points. Then, we used piecewise linear regression and autoregressive integrated moving average (ARIMA) to compare the trends in searches for Puff Bar for the four (4) periods.

Results

Before the initial announcement to ban non-tobacco flavored e-cigarettes, online search queries (per 10 million Google searches) for Puff Bar were slowly rising at a rate of 0.58 queries per week (95%CI: -0.80 – 1.97). Following the announcement, searches for Puff Bar increased significantly at a rate of 16.61 queries per week (95%CI: 12.13 – 21.10). The rate of searches for Puff Bar then increased exponentially at 40.08 queries per week (95%CI: 27.32 – 52.84) following the FDA flavor ban, which excluded disposable e-cigarettes. Then, the rate of increase declined but remained relatively stable at 3.67 queries per week (95%CI: 0.69–6.65) until the FDA's notice to remove flavored Puff Bar products from the market. Following this notice, the rate of searches for Puff Bar significantly declined (rate: -4.97 queries per week; 95%CI: -5.40—-4.54).

Conclusions

The tracking of online search data demonstrates rapid public recognition of the FDA's announcements of tobacco regulatory actions.
Implementation barriers and enablers of midwifery group practice for vulnerable women: a qualitative study in a tertiary urban Australian health service
Authors: Smith Patricia A , Kilgour Catherine , Rice Deann , Callaway Leonie K , Martin Elizabeth K
Published: October 2022

Background

Maternity services have limited formalised guidance on planning new services such as midwifery group practice for vulnerable women, for example women with a history of substance abuse (alcohol, tobacco and other drugs), mental health challenges, complex social issues or other vulnerability. Continuity of care through midwifery group practice is mostly restricted to women with low-risk pregnancies and is not universally available to vulnerable women, despite evidence supporting benefits of this model of care for all women. The perception that midwifery group practice for vulnerable women is a high-risk model of care lacking in evidence may have in the past, thwarted implementation planning studies that seek to improve care for these women. We therefore aimed to identify the barriers and enablers that might impact the implementation of a midwifery group practice for vulnerable women.

Methods

A qualitative context analysis using the Consolidated Framework for Implementation Research was conducted at a single-site tertiary health facility in Queensland, Australia. An interdisciplinary group of stakeholders from a purposeful sample of 31 people participated in semi-structured interviews. Data were analysed using manual and then Leximancer computer assisted methods. Themes were compared and mapped to the Framework.

Results

Themes identified were the woman’s experience, midwifery workforce capabilities, identifying “gold standard care”, the interdisciplinary team and costs. Potential enablers of implementation included perceptions that the model facilitates a relationship of trust with vulnerable women, that clinical benefit outweighs cost and universal stakeholder acceptance. Potential barriers were: potential isolation of the interdisciplinary team, costs and the potential for vicarious trauma for midwives.

Conclusion

There was recognition that the proposed model of care is supported by research and a view that clinical benefits will outweigh costs, however supervision and support is required for midwives to manage and limit vicarious trauma. An interdisciplinary team structure is also an essential component of the service design. Attention to these key themes, barriers and enablers will assist with identification of strategies to aid successful implementation. Australian maternity services can use our results to compare how the perceptions of local stakeholders might be similar or different to the results presented in this paper.
Do people perceive benefits in the use of social prescribing to address loneliness and/or social isolation? A qualitative meta-synthesis of the literature
Authors: Liebmann M. , Pitman A. , Hsueh Yung-Chia , Bertotti M. , Pearce E.
Published: October 2022

Social prescribing is a means by which clinical services can link individuals who have psychological, social and/or practical needs with non-clinical services within their local community. There is a lack of empirical evidence investigating whether social prescribing helps such individuals and which interventions are the most effective and accepted by them to address their loneliness. This meta-synthesis aimed to synthesise findings from qualitative studies exploring experiences of people (of any age) who participated in any social prescribing intervention aimed at loneliness and/or social isolation to ascertain whether they felt it helped address loneliness/isolation and the potential mechanisms by which this might occur. We conducted a systematic search of 5 electronic databases and 4 other databases that would yield grey literature in April 2021 to identify qualitative articles on this topic written in English or French. We assessed the quality of the included studies using recognised tools, and synthesised findings using the approach of thematic analysis. We identified 19 records analysed (e.g. journal articles) from 18 studies meeting inclusion criteria. Our analysis identified three themes: (1) increased sense of wellbeing (with six subthemes), (2) factors that engendered an ongoing desire to connect with others, and (3) perceived drawbacks of social prescribing. These themes illustrate the benefits and difficulties people perceive in social prescribing programmes addressing loneliness and social isolation, with an overall balance of more benefits than drawbacks in social prescribing participation. However, given the unhelpful aspects of social prescribing identified by some participants, greater thought should be given to potential harms. Moreover, further qualitative and quantitative research is needed to better understand mechanisms and effectiveness, and how different components of social prescribing might be best matched to individual participants.
Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition
Authors: Breeur Marie , Ferrari Pietro , Dossus Laure , Jenab Mazda , Johansson Mattias , Rinaldi Sabina , Travis Ruth C. , His Mathilde , Key Tim J. , Schmidt Julie A. , Overvad Kim , Tjønneland Anne , Kyrø Cecilie , Rothwell Joseph A. , Laouali Nasser , Severi Gianluca , Kaaks Rudolf , Katzke Verena , Schulze Matthias B. , Eichelmann Fabian , Palli Domenico , Grioni Sara , Panico Salvatore , Tumino Rosario , Sacerdote Carlotta , Bueno-de-Mesquita Bas , Olsen Karina Standahl , Sandanger Torkjel Manning , Nøst Therese Haugdahl , Quirós J. Ramón , Bonet Catalina , Barranco Miguel Rodríguez , Chirlaque María-Dolores , Ardanaz Eva , Sandsveden Malte , Manjer Jonas , Vidman Linda , Rentoft Matilda , Muller David , Tsilidis Kostas , Heath Alicia K. , Keun Hector , Adamski Jerzy , Keski-Rahkonen Pekka , Scalbert Augustin , Gunter Marc J. , Viallon Vivian
Published: October 2022

Background

Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations.

Methods

We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty.

Results

Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk.

Conclusions

These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
Mitigation potential of individual and combined dietary supplementation of local Bentonite Clay and Distillery Sludge against Ochratoxin-A induced toxicity in broilers
Authors: Awais Mian Muhammad , Mehtab Ujala , Anwar Muhammad Irfan , Hameed Muhammad Raza , Akhtar Masood , Raza Ahmad , Aisha Riffat , Muhammad Faqir , Saleemi Muhammad Kashif , Fayyaz Ahad
Published: October 2022

Background

This study aimed to evaluate the ameliorative effects of dietary supplementation of local bentonite clay (BN) and distillery sludge (DS) alone and in combination on ochratoxin-A (OTA) induced toxicity in broilers. For this purpose, day-old-broiler chicks (n = 270) were procured from the local market and reared under standard management conditions. After 7 days of acclimatization, birds were divided into 2 main groups A and B with respect to OTA inclusion level in feed, each with four sub-groups viz. A1-A4, each challenged with OTA at a dietary inclusion level of 250 µg/kg feed and B1-B4, each challenged with OTA at the level of 500 µg/kg feed and a common control group that was fed with basal feed throughout the experiment. In groups A and B, BN and DS were administered with feed at the rate of 10 g/kg of feed and 5 g/kg of feed alone and in combination, respectively.

Results

Results showed that OTA administration alone resulted in poor feed conversion ratio (FCR) and immunological responses along with increased serum levels of alanine transaminase (ALT), Aspartate transaminase (AST), urea and creatinine (P < 0.05). A significant decrease (P < 0.05) in serum protein levels (albumin, globulin and total protein) was also observed in OTA-fed groups in a dose-dependent manner. The addition of BN at 10 g/kg of OTA-contaminated feed resulted in better FCR and immunological responses as compared to those fed OTA only. The BN supplementation also conferred protection against elevation of serum biochemical parameters when compared with OTA-fed groups. However, the addition of DS could not provide significant protection (P > 0.05) on alteration of serum biochemical parameters in response to the OTA induced toxicity. The combined supplementation of BN and DS resulted in amelioration of OTA-induced toxicity and showed improved FCR, immunological, hematological and serum biochemical parameters (P < 0.05) when compared with other groups. Similarly, BN and DS resulted in a significant decline (P < 0.05) in the OTA tissue residues compared with other groups and control.

Conclusion

In conclusion, combined dietary supplementation of BN (10 mg/kg) and DS (05 mg/kg) in feed reduced the toxic effects of OTA contamination at levels of 250 and 500 µg/kg of feed in broilers. So, the combination products of BN and DS may be successfully developed for use in poultry for protection against OTA-induced toxicity in broilers.
Tumor buster - where will the CAR-T cell therapy ‘missile’ go?
Authors: Qu Chunrun , Zhang Hao , Cao Hui , Tang Lanhua , Mo Haoyang , Liu Fangkun , Zhang Liyang , Yi Zhenjie , Long Lifu , Yan Luzhe , Wang Zeyu , Zhang Nan , Luo Peng , Zhang Jian , Liu Zaoqu , Ye Weijie , Liu Zhixiong , Cheng Quan
Published: October 2022

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.
Prognostic significance of combined α-fetoprotein and CA19-9 for hepatocellular carcinoma after hepatectomy
Authors: Zhang Jie , Qin Shang Dong , Li Yan , Lu Fei , Gong Wen Feng , Zhong Jian Hong , Ma Liang , Zhao Jing Fei , Zhan Guo Hua , Li Peng Zhan , Song Bin , De Xiang Bang
Published: October 2022

Background

The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high levels of α-fetoprotein (AFP), a common prognostic indicator for HCC. Here, we assessed whether the combination of presurgical serum levels of AFP and carbohydrate antigen 19-9 (CA19-9) can predict the prognosis of HCC patients after hepatectomy.

Methods

The clinicopathological characteristics and post-hepatectomy outcomes of 711 HCC patients were retrospectively reviewed. The patients were classified into three groups based on whether their preoperative serum levels of both AFP and CA19-9 were higher than the respective cut-offs of 400 ng/ml and 37 U/ml [double positive (DP)], the level of only one marker was higher than the cut-off [single positive (SP)], or neither level was higher than the cut-off [negative (N)]. The overall survival (OS) and recurrence-free survival (RFS) rates were estimated using Kaplan–Meier curves. Univariate and multivariate survival analyses were performed to identify the clinicopathological factors significantly associated with HCC prognosis.

Results

The 1-year, 3-year, and 5-year RFS and OS rates in the N group were significantly higher than those in the SP group, while the DP group showed the lowest rates. Multivariate Cox regression analysis showed that large tumor size (> 5 cm), multiple tumors (≥ 2), incomplete tumor capsule, positive microvascular invasion, Barcelona Clinic Liver Cancer C stage, and CA19-9 level > 37 U/mL were independent risk factors for RFS and OS in HCC patients. Moreover, aspartate aminotransferase levels > 40 U/L proved to be an independent prognostic factor for OS.

Conclusion

The combination of serum AFP and CA19-9 levels may be a useful prognostic marker for HCC patients after hepatectomy.
CapG promoted nasopharyngeal carcinoma cell motility involving Rho motility pathway independent of ROCK
Authors: Fu Ying , Zhang Xiuzhi , Liang Xujun , Chen Yongheng , Chen Zhuchu , Xiao Zhefeng
Published: October 2022

Background

Gelsolin-like capping actin protein (CapG) modulates actin dynamics and actin-based motility with a debatable role in tumorigenic progression. The motility-associated functions and potential molecular mechanisms of CapG in nasopharyngeal carcinoma (NPC) remain unclear.

Methods

CapG expression was detected by immunohistochemistry in a cohort of NPC tissue specimens and by Western blotting assay in a variety of NPC cell lines. Loss of function and gain of function of CapG in scratch wound-healing and transwell assays were performed. Inactivation of Rac1 and ROCK with the specific small molecular inhibitors was applied to evaluate CapG’s role in NPC cell motility. GTP-bound Rac1 and phosphorylated-myosin light chain 2 (p-MLC2) were measured in the ectopic CapG overexpressing cells. Finally, CapG-related gene set enrichment analysis was conducted to figure out the significant CapG-associated pathways in NPC.

Results

CapG disclosed increased level in the poorly differentiated NPC tissues and highly metastatic cells. Knockdown of CapG reduced NPC cell migration and invasion in vitro, while ectopic CapG overexpression showed the opposite effect. Ectopic overexpression of CapG compensated for the cell motility loss caused by simultaneous inactivation of ROCK and Rac1 or inactivation of ROCK alone. GTP-bound Rac1 weakened, and p-MLC2 increased in the CapG overexpressing cells. Bioinformatics analysis validated a positive correlation of CapG with Rho motility signaling, while Rac1 motility pathway showed no significant relationship.

Conclusions

The present findings highlight the contribution of CapG to NPC cell motility independent of ROCK and Rac1. CapG promotes NPC cell motility at least partly through MLC2 phosphorylation and contradicts with Rac1 activation.
Lrpap1 deficiency leads to myopia through TGF-β-induced apoptosis in zebrafish
Authors: Liu Shanshan , Chen Ting , Chen Binghao , Liu Yijun , Lu Xiaohe , Li Jiali
Published: October 2022

Background

Frameshift mutations in LRPAP1 are responsible for autosomal recessive high myopia in human beings but its underlying mechanism remains elusive. This study aims to investigate the effect of LRPAP1 defect on ocular refractive development and its involved mechanism.

Methods

A lrpap1 mutant zebrafish line with homozygous frameshift mutation was generated by CRISPR/Cas9 technology and confirmed by Sanger sequencing. The ocular refractive phenotype was analyzed by calculating the relative refractive error (RRE) with vivo photography and histological analysis at different development stages, together with examining ocular structure change via transmission electron microscopy. Further, RNA sequencing and bioinformatics analysis were performed. The potentially involved signaling pathway as well as the interacted protein were investigated in vivo.

Results

The lrpap1 homozygous mutant zebrafish line showed myopic phenotype. Specifically, the mutant lines showed larger eye axial length-to-body length in one-month old individuals and a myopic shift with an RRE that changed after two months. Collagen fibers became thinning and disordered in the sclera. Further, RNA sequencing and bioinformatics analysis indicated that apoptosis signaling was activated in mutant line; this was further confirmed by acridine orange and TUNEL staining. Moreover, the expression of TGF-β protein was elevated in the mutant lines. Finally, the treatment of wild-type embryos with a TGF-β agonist aggravated the degree of eyeball apoptosis; conversely, the use of a TGF-β inhibitor mitigated apoptosis in mutant embryos.

Conclusion

The study provides functional evidence of a link between lrpap1 and myopia, suggesting that lrpap1 deficiency could lead to myopia through TGF-β-induced apoptosis signaling.
LotuS2: an ultrafast and highly accurate tool for amplicon sequencing analysis
Authors: Özkurt Ezgi , Fritscher Joachim , Soranzo Nicola , Ng Duncan Y. K. , Davey Robert P. , Bahram Mohammad , Hildebrand Falk
Published: October 2022

Background

Amplicon sequencing is an established and cost-efficient method for profiling microbiomes. However, many available tools to process this data require both bioinformatics skills and high computational power to process big datasets. Furthermore, there are only few tools that allow for long read amplicon data analysis. To bridge this gap, we developed the LotuS2 (less OTU scripts 2) pipeline, enabling user-friendly, resource friendly, and versatile analysis of raw amplicon sequences.

Results

In LotuS2, six different sequence clustering algorithms as well as extensive pre- and post-processing options allow for flexible data analysis by both experts, where parameters can be fully adjusted, and novices, where defaults are provided for different scenarios.

We benchmarked three independent gut and soil datasets, where LotuS2 was on average 29 times faster compared to other pipelines, yet could better reproduce the alpha- and beta-diversity of technical replicate samples. Further benchmarking a mock community with known taxon composition showed that, compared to the other pipelines, LotuS2 recovered a higher fraction of correctly identified taxa and a higher fraction of reads assigned to true taxa (48% and 57% at species; 83% and 98% at genus level, respectively). At ASV/OTU level, precision and F-score were highest for LotuS2, as was the fraction of correctly reported 16S sequences.

Conclusion

LotuS2 is a lightweight and user-friendly pipeline that is fast, precise, and streamlined, using extensive pre- and post-ASV/OTU clustering steps to further increase data quality. High data usage rates and reliability enable high-throughput microbiome analysis in minutes.

Availability

LotuS2 is available from GitHub, conda, or via a Galaxy web interface, documented at http://lotus2.earlham.ac.uk/.
Study on the efficacy of amorphous calcium carbonate as a consolidant for calcareous matrix
Authors: Wang Wenwen , Wang Shuzhe , Liu Qiang , Wang Xiaofei , Zhu Jianfeng , Luo Hongjie , Ji Shidong
Published: October 2022

The popular involvement of amorphous calcium carbonate (ACC) in organisms, usually via a complicated non-classical crystallization pathway, has aroused interest in the scientific community. In recent years, a lot of work has been carried out for the preparation and application of ACC. In this paper, the effectiveness of ACC for the consolidation of calcareous matrix was evaluated. ACC was synthesized through direct carbonation of calcium oxide in ethanol and was introduced into simulated samples as consolidant. A comprehensive study for the assessment of protective effect was carried out by testing surface strength, chromaticity, compressive strength, water vapor permeability, water absorption and freezing–thawing resistance. The results showed that the addition of ACC could significantly improve the surface strength, compressive strength and weatherability of treated samples, while it had only a slight influence on color difference and water vapor permeability. It was confirmed that ACC could connect the loose calcite particles by ‘spot welding’ through heterogeneous nucleation and growth processes. As a consolidant, it demonstrated its merits in this study and could be proposed as an alternative for the protection of weathered calcareous stones.
Electric field responsive nanotransducers for glioblastoma
Authors: Jain Akhil , Jobson Isobel , Griffin Michaela , Rahman Ruman , Smith Stuart , Rawson Frankie J.
Published: October 2022

Background

Electric field therapies such as Tumor Treating Fields (TTFields) have emerged as a bioelectronic treatment for isocitrate dehydrogenase wild-type and IDH mutant grade 4 astrocytoma Glioblastoma (GBM). TTFields rely on alternating current (AC) electric fields (EF) leading to the disruption of dipole alignment and induced dielectrophoresis (DEP) during cytokinesis. Although TTFields have a favourable side effect profile, particularly compared to cytotoxic chemotherapy, survival benefits remain limited (~ 4.9 months) after an extensive treatment regime (20 hours/day for 18 months). The cost of the technology also limits its clinical adoption worldwide. Therefore, the discovery of new technology that can enhance both the therapeutic efficiency and efficacy of these TTFields will be of great benefit to cancer treatment and decrease healthcare costs worldwide.

Methods

In this work, we report the role of electrically conductive gold (GNPs), dielectric silica oxide (SiO2), and semiconductor zinc oxide (ZnO) nanoparticles (NPs) as transducers for enhancing EF mediated anticancer effects on patient derived GBM cells. Physicochemical properties of these NPs were analyzed using spectroscopic, electron microscopy, and light-scattering techniques.

Results

In vitro TTFields studies indicated an enhanced reduction in the metabolic activity of patient-derived Glioma INvasive marginal (GIN 28) and Glioma contrast enhanced core (GCE 28) GBM cells in groups treated with NPs vs. control groups, irrespective of NPs dielectric properties. Our results indicate the inorganic NPs used in this work enhance the intracellular EF effects that could be due to the virtue of bipolar dielectrophoretic and electrophoretic effects.

Conclusions

This work presents preliminary evidence which could help to improve future EF applications for bioelectronic medicine. Furthermore, the merits of spherical morphology, excellent colloidal stability, and low toxicity, make these NPs ideal for future studies for elucidating the detailed mechanism and efficacy upon their delivery in GBM preclinical models.
NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma
Authors: Tsien Christina I. , Pugh Stephanie L. , Dicker Adam P. , Raizer Jeffrey J. , Matuszak Martha M. , Lallana Enrico C. , Huang Jiayi , Algan Ozer , Deb Nimisha , Portelance Lorraine , Villano John L. , Hamm John T. , Oh Kevin S. , Ali Arif N. , Kim Michelle M. , Lindhorst Scott M. , Mehta Minesh P.
Published: October 2022

PURPOSE

To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities.

METHODS

NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression.

RESULTS

From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM.

CONCLUSION

To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.
Autopsy Study of Testicles in COVID-19: Upregulation of Immune-Related Genes and Downregulation of Testis-Specific Genes
Authors: Basolo Alessio , Poma Anello Marcello , Macerola Elisabetta , Bonuccelli Diana , Proietti Agnese , Salvetti Alessandra , Vignali Paola , Torregrossa Liborio , Evangelisti Laura , Sparavelli Rebecca , Giannini Riccardo , Ugolini Clara , Basolo Fulvio , Santini Ferruccio , Toniolo Antonio
Published: October 2022

Context

Infection by SARS-CoV-2 may be associated with testicular dysfunction that could affect male fertility.

Objective

Testicles of fatal COVID-19 cases were investigated to detect virus in tissue and to evaluate histopathological and transcriptomic changes.

Methods

Three groups were compared: (a) uninfected controls (subjects dying of trauma or sudden cardiac death; n = 10); (b) subjects dying of COVID-19 (virus-negative in testes; n = 15); (c) subjects dying of COVID-19 (virus-positive in testes; n = 9). SARS-CoV-2 genome and nucleocapsid antigen were probed using RT-PCR, in situ hybridization, and immunohistochemistry (IHC). Infiltrating leukocytes were typed by IHC. mRNA transcripts of immune-related and testis-specific genes were quantified using the nCounter method.

Results

SARS-CoV-2 was detected in testis tissue of 9/24 (37%) COVID-19 cases accompanied by scattered T-cell and macrophage infiltrates. Size of testicles and counts of spermatogenic cells were not significantly different among groups. Analysis of mRNA transcripts showed that in virus-positive testes immune processes were activated (interferon-alpha and -gamma pathways). By contrast, transcription of 12 testis-specific genes was downregulated, independently of virus positivity in tissue. By IHC, expression of the luteinizing hormone/choriogonadotropin receptor was enhanced in virus-positive compared to virus-negative testicles, while expression of receptors for androgens and the follicle-stimulating hormone were not significantly different among groups.

Conclusion

In lethal COVID-19 cases, infection of testicular cells is not uncommon. Viral infection associates with activation of interferon pathways and downregulation of testis-specific genes involved in spermatogenesis. Due to the exceedingly high numbers of infected people in the pandemic, the impact of virus on fertility should be further investigated.
The Association of Inflammatory Factors With Peripheral Neuropathy: The Study of Women's Health Across the Nation
Authors: Sanders Wade M , Harlow Siobán D , Ylitalo Kelly R , Lange-Maia Brittney S , Leis Aleda M , McConnell Daniel S , Karvonen-Gutierrez Carrie A
Published: October 2022

Purpose

Previous work has focused on the role of diabetes in peripheral neuropathy (PN), but PN often occurs before, and independently from, diabetes. This study measures the association of cardiometabolic and inflammatory factor with PN, independent of diabetes.

Methods

Study of Women's Health Across the Nation participants (n = 1910), ages 60 to 73 (mean 65.6) were assessed for PN by symptom questionnaire and monofilament testing at the 15th follow-up visit (V15). Anthropometric measures and biomarkers were measured at study baseline approximately 20 years prior, and C-reactive protein (CRP) and fibrinogen were measured longitudinally. Log-binomial regression was used to model the association between metabolic syndrome (MetS), obesity (≥35 body mass index), CRP, and fibrinogen with PN, adjusting for sociodemographic and health behavior measures.

Results

Baseline MetS [prevalence ratio (PR) 1.79, 95% CI (1.45, 2.20)], obesity [PR 2.08 (1.65, 2.61)], median CRP [PR 1.32 per log(mg/dL), (1.20, 1.45)], and mean fibrinogen (PR 1.28 per 100 mg/dL, (1.09, 1.50)] were associated with PN symptoms at V15. After excluding participants with baseline diabetes or obesity, MetS [PR 1.59 (1.17, 2.14)] and CRP [PR 1.19 per log(mg/dL), (1.06, 1.35)] remained statistically significantly associated with PN. There was a negative interaction between MetS and obesity, and the association between these conditions and PN was mediated by CRP.

Conclusions

Cardiometabolic factors and inflammation are significantly associated with PN, independent of diabetes and obesity. CRP mediates the relationship of both obesity and MetS with PN, suggesting an etiological role of inflammation in PN in this sample.
Χώρος, πολιτική και συλλογική δράση την εποχή της παγκοσμιοποίησης
Authors: Κούκα Μαρτίν
Published: October 2022

Η παρούσα διατριβή εμβαθύνει στην ανεξάρτητη συλλογική δράση για την προστασία του χώρου στην πρωτεύουσα της Αλβανίας, τα Τίρανα. Μετά την πτώση του κομμουνισμού η πρωτεύουσα μεγάλωσε, λόγω της εσωτερικής μετανάστευσης, και η ζήτηση για στέγαση αυξήθηκε σημαντικά. Η απελευθέρωση της αγορά έδωσε ώθηση στο σχηματισμό κατασκευαστικών εταιρειών, οι οποίες έχτιζαν κατοικίες αρχικά σε ανοιχτούς και δημόσιους χώρους και, αργότερα, στη θέση παλιών και παραδοσιακών κατοικιών ή κτηρίων. Η πολιτική ηγεσία όχι μόνο δεν εμπόδισε τις ανεξέλεγκτες κατασκευές, αλλά αντίθετα τις βοήθησε μέσω των ειδικών νόμων που ψήφισε. Ως αποτέλεσμα η πόλη μεγάλωσε χαοτικά. Η ανεξέλεγκτη αστική ανάπτυξη έχει προκαλέσει πολλά προβλήματα στους κατοίκους, οι οποίοι, ωστόσο, δεν φαίνονται διατεθειμένοι να αντιδράσουν συλλογικά και για να προστατεύσουν τους εναπομείναντες ανοιχτούς χώρους της πόλης. Η έρευνα βασίζεται στα νοήματα που πολίτες των Τιράνων αποδίδουν στη συλλογική δράση. Ως σημείο αναφοράς λήφθηκε η διαμαρτυρία για την προστασία του Εθνικού Θεάτρου της Αλβανίας, η σημαντικότερη συλλογική δράση στην πρωτεύουσα που διήρκησε πάνω από δυο χρόνια. Για τη συλλογή των δεδομένων έλαβα συνολικά 44 ημιδομημένες συνεντεύξεις με κατοίκους των Τιράνων και διαμαρτυρόμενους στο Θέατρο. Η εύρεση και η επιλογή των συμμετεχόντων έγινε μέσω της τεχνικής της χιονοστιβάδας, ενώ οι αφηγήσεις τους αναλύθηκαν από την οπτική της ερμηνευτικής θεωρίας.Τα ευρήματα της έρευνας δεν είναι ενθαρρυντικά. Όσον αφορά στις ανεξάρτητες συλλογικές προσπάθειες, οι κάτοικοι της πρωτεύουσας δεν είναι δραστήριοι πολίτες. Οι λόγοι της φαινομενικής απάθειάς τους αναζητήθηκαν σε δυο περιόδους της ζωής τους, την κομμουνιστική περίοδο και τη περίοδο μετά την πτώση του. Ο φόβος αντίδρασης κατά της κυβέρνησης επί κομμουνισμού φαίνεται πως διατηρήθηκε στους μεγάλους στην ηλικία συμμετέχοντες στην έρευνα, οι οποίοι είναι προσεκτικοί σχετικά με τις δημόσιες δηλώσεις τους και συνιστούν στα παιδιά τους να είναι το ίδιο προσεκτικοί. Μεγαλύτερη επεξηγηματική αξία για τη μη συμμετοχής σε συλλογικές προσπάθειες έχουν φυσικά οι παράγοντες της μετακομμουνιστικής περιόδου. Ο φόβος αντίδρασης κατά της κυβέρνησης παραμένει σημαντικός παράγοντας αποχής από τη συλλογική δράση. Άλλοι παράγοντες που συμβάλλουν στην αποχή από τη συλλογική δράση είναι οι οικονομικές συνθήκες, η λειτουργία των θεσμών της χώρας, καθώς και η δράση διεθνών παραγόντων, όπως είναι οι ξένοι πολιτικοί, διεθνείς οργανώσεις, ξένες αντιπροσωπείες στην Αλβανία, κλπ, τους οποίους οι Αλβανοί πολίτες συνήθως εμπιστεύονται περισσότερο απ’ότι τους ντόπιους παράγοντες. Όταν οι οικονομικές συνθήκες είναι δυσχερείς, τότε οι πολίτες θα φροντίσουν να καλύψουν τις άμεσες ανάγκες τους παρά να διαδηλώνουν στους δρόμους για την προστασία του χώρου. Επιπλέον, όταν οι διεθνείς παράγοντες συγχαίρουν την κυβέρνηση γενικά για το έργο της, τότε οι πολίτες δεν έχουν λόγους να εναντιωθούν στις αποφάσεις της σχετικά με τη μεταχείριση του χώρου.
Το Φως στην Αριστοτελική Φυσική
Authors: Τραϊανού Απόστολος
Published: October 2022

Στην παρούσα Διδακτορική Διατριβή μελετάται λεπτομερώς και πολύπλευρα το φως στον Αριστοτέλη, με βάση τα δεδομένα που αντλούνται από τα κείμενά του. Στο πρώτο κεφάλαιο παρουσιάζεται σύντομα ο αριστοτελικός φυσικός κόσμος. Στο δεύτερο κεφάλαιο εξετάζονται η φύση και τα χαρακτηριστικά του φωτός ως αυτού που είναι. Αρχικά, εξηγούνται οι λόγοι για τους οποίους ο σταγειρίτης φιλόσοφος απέρριπτε την άποψη ότι το φως είναι ένα είδος πυρός. Γι’ αυτόν το φως δεν είναι ένα σώμα αλλά ενεργή διαφάνεια, το "διαφανές" που είναι ενεργά διαφανές. Από τη διερεύνηση της σχέσης του "διαφανούς" με τα φυσικά σώματα συμπεραίνεται ότι αυτό συνιστά ένα εκτατό, αλλά ασώματο, φυσικό αίτιο έκδηλης ή λανθάνουσας διαφάνειας στο καθένα. Έτσι, το φως είναι μία φυσική κατάσταση στην οποία απαντά αυτό το αίτιο. Στο συγκεκριμένο κεφάλαιο εξετάζονται και οι προεκτάσεις που θα παρουσιάζει η υπόθεση της ύπαρξης του "διαφανούς" στη φυσική και την κοσμολογία του Αριστοτέλη και η σχέση του ίδιου και του φωτός με την έννοια της μεταβολής. Επιπλέον, επιχειρείται μία εξήγηση των διαβαθμίσεων της ενεργής διαφάνειας, που παρατηρούμε στη φύση, και προσδιορίζεται η πρωτοτυπία της αριστοτελικής θεώρησης της φύσης του φωτός, η οποία θα πρέπει να θεωρείται μία τομή στον χώρο της μελέτης της τελευταίας. Στο τρίτο κεφάλαιο εξετάζεται το φως από την πλευρά της όρασης. Αναδεικνύεται ότι ο φιλόσοφος κατανοεί σχετικά καλά και εφαρμόζει την ανάκλαση του φωτός, μελετάται η φυσική της όρασης, προσδιορίζεται ο ακριβής ρόλος του φωτός σε αυτήν, ενώ, επίσης, τονίζεται η αντίθεση της χρήσης των οπτικών ακτίνων στις εξηγήσεις του ίδιου για τα οπτικά φαινόμενα ως προς την άποψή του για τη φυσική της όρασης και αναδεικνύεται ότι αυτή η αντίθεση δεν είναι εύκολα εξηγήσιμη. Το τέταρτο και τελευταίο κεφάλαιο του πονήματος αφιερώνεται στην αμφίδρομη αιτιακή σχέση του φωτός με τη θερμότητα και κυρίως στον ρόλο του φωτός ως του αιτίου της θέρμανσης των σωμάτων της υποσελήνιας περιοχής του κόσμου από τον ήλιο. Εδώ τεκμηριώνεται ότι ο Αριστοτέλης δέχεται τον εν λόγω ρόλο του ηλιακού φωτός, ειδικά στις βιολογικές του πραγματείες, και γιατί κάτι τέτοιο θα ήταν λογικό στην ώριμη κοσμολογία του. Επίσης, εξετάζεται η θεωρία που παραθέτει σε κοσμολογικά πλαίσια για την παραγωγή του φωτός και της θερμότητας από τον ήλιο και τα άλλα ουράνια σώματα και προτείνεται, ως μία πιθανή λύση στο πρόβλημα της μη λειτουργικότητάς της, η θεώρηση του φωτός ως αιτίου θέρμανσης και στο πλαίσιό της. Καθώς το ηλιακό φως είναι το αίτιό της, αιτιολογούνται οι κανονικές μεταβολές της θέρμανσης της υποσελήνιας περιοχής από τον ήλιο και αναδεικνύεται αναλυτικά η καθοριστική σημασία του ηλιακού φωτός γι’ αυτή την περιοχή. Πάντως, όπως συμπεραίνεται, η αμφίδρομη αιτιακή σχέση του φωτός με τη θερμότητα αποτελεί μία μη εξηγήσιμη πλευρά του φυσικού κόσμου.
Effects of the COVID-19 pandemic on university-based research conduct and training: Exploring university-based researchers’ perspectives and experiences
Authors: Ory Marcia G. , Lee Shinduk , Radcliff Tiffany A. , Jani Sagar , Rice-Ficht Allison , Waer Amy L.
Published: October 2022

Background: The academic environment is critical for advancing knowledge through research and training of students who will serve as researchers, advocates, and leaders in the future, yet there is limited data on how the higher institution-based research enterprise is being impacted by the coronavirus disease 2019 (COVID-19) pandemic. The current study examines the perceived and expected impact of COVID-19 on engaging in a higher education institution setting, particularly focusing on student engagement in research and conduct of human subject research (HSR).

Method: The authors collected an online survey with faculty and staff in a large US university system focused on education, research, and service (6/8/2020-7/10/2020; N=709). The authors performed bivariate and multivariable logistic regression models to examine the differences in research impact by HSR.

Results: The majority of survey respondents (i.e., faculty and staff from a large US university system) perceived and expected at least some impact of COVID-19 on research and reported the impact to be negative. Researchers reported increased challenges in recruiting students for research activities and providing research-related learning opportunities for students. While COVID-19 impacted both HSR and non-HSR, HSR investigators have been disproportionately impacted by the pandemic.

Conclusions: Efforts are needed to further understand and overcome research challenges so that the university-based research environment can flourish for all researchers across disciplines and overcome the potentially lost learning opportunities for students. Lessons learned will help address future challenges to academic research activities and providing student research training.
The effect of the scale of grant scoring on ranking accuracy
Authors: Visscher Peter M. , Yengo Loic
Published: October 2022

In this study we quantify the accuracy of scoring the quality of research grants using a finite set of distinct categories (1, 2, …., k), when the unobserved grant score is a continuous random variable comprising a true quality score and measurement error, both normally distributed. We vary the number of categories, the number of assessors that score the same grant and a signal-to-noise ratio parameter. We show that the loss of information of scoring a small number of categories (k > 5) compared to scoring on a continuous scale is very small, so that increasing the number of scoring categories is unlikely to lead to an improvement in the outcomes of scoring systems. In addition, we model the effect of grant assessors scoring too close to the mean and show that this results in only a very small reduction in the accuracy of scoring.
Chemical equilibrium model comprising calcaneus bone mineral density, low-density lipoprotein cholesterol, and physical work capacity in premenopausal women
Authors: Mitsuhashi Kazuto , Imagawa Yasunori , Kojima Yuta , Ishii Naokata , Kishimoto Yasushi
Published: October 2022

Background: During menopause, bone density decreases, and low-density lipoprotein cholesterol (LDL-C) rapidly increases; a decrease in the estrogen level is a common factor in these phenomena. Methods: In this study, we focused on the fact that menopause is a spontaneous process, and aimed to derive the conditions that mitigate the decline in the osteo sono-assessment index (OSI), an index of bone mineral density (BMD), using a chemical equilibrium model. We attempted to establish the relationship between variables related to female hormone secretion (OSI, LDL-C) and a variable related to work capacity (physical work capacity [PWC] at 75% of maximal heart rate) by analogy, using the fact that Gibbs free energy, a thermodynamic variable related to spontaneous change, is related by three variables. Results: Consequently, if linearity is established between PWC and OSI when LDL-C is used as the standard, then the analogy of chemical equilibrium can be established between the deviation values of these three variables, with equilibrium constant K. Finally, the theoretically determined equilibrium model with constant K was applied to data obtained from the Sports Program Service (SPS) of the Yokohama Sports Medical Center. Conclusions: The present study suggests that the decrease in bone density could be alleviated by promoting an increase in LDL-C or by mitigating the decrease in PWC. In discussing personal health, mitigating bone density loss and maintaining a high work capacity are important components, which should also take into account the appropriate levels of LDL-C.