bluuebunny/crossref_metadata_2025 huggingface dataset:
Classifying patient and professional voice in social media health posts
Authors: Alex Beatrice , Whyte Donald , Duma Daniel , Owen Roma English , Fairley Elizabeth A. L.
Published: August 2021

Background

Patient-based analysis of social media is a growing research field with the aim of delivering precision medicine but it requires accurate classification of posts relating to patients’ experiences. We motivate the need for this type of classification as a pre-processing step for further analysis of social media data in the context of related work in this area. In this paper we present experiments for a three-way document classification by patient voice, professional voice or other. We present results for a convolutional neural network classifier trained on English data from two different data sources (Reddit and Twitter) and two domains (cardiovascular and skin diseases).

Results

We found that document classification by patient voice, professional voice or other can be done consistently manually (0.92 accuracy). Annotators agreed roughly equally for each domain (cardiovascular and skin) but they agreed more when annotating Reddit posts compared to Twitter posts. Best classification performance was obtained when training two separate classifiers for each data source, one for Reddit and one for Twitter posts, when evaluating on in-source test data for both test sets combined with an overall accuracy of 0.95 (and macro-average F1 of 0.92) and an F1-score of 0.95 for patient voice only.

Conclusion

The main conclusion resulting from this work is that combining social media data from platforms with different characteristics for training a patient and professional voice classifier does not result in best possible performance. We showed that it is best to train separate models per data source (Reddit and Twitter) instead of a model using the combined training data from both sources. We also found that it is preferable to train separate models per domain (cardiovascular and skin) while showing that the difference to the combined model is only minor (0.01 accuracy). Our highest overall F1-score (0.95) obtained for classifying posts as patient voice is a very good starting point for further analysis of social media data reflecting the experience of patients.
Long-term persistence of crAss-like phage crAss001 is associated with phase variation in Bacteroides intestinalis
Authors: Shkoporov Andrey N. , Khokhlova Ekaterina V. , Stephens Niamh , Hueston Cara , Seymour Samuel , Hryckowian Andrew J. , Scholz Dimitri , Ross R. Paul , Hill Colin
Published: August 2021

Background

The crAss-like phages are ubiquitous and highly abundant members of the human gut virome that infect commensal bacteria of the order Bacteroidales. Although incapable of lysogeny, these viruses demonstrate long-term persistence in the human gut microbiome, dominating the virome in some individuals.

Results

Here we show that rapid phase variation of alternate capsular polysaccharides in Bacteroides intestinalis cultures plays an important role in a dynamic equilibrium between phage sensitivity and resistance, allowing phage and bacteria to multiply in parallel. The data also suggests the role of a concomitant phage persistence mechanism associated with delayed lysis of infected cells, similar to carrier state infection. From an ecological and evolutionary standpoint, this type of phage-host interaction is consistent with the Piggyback-the-Winner model, which suggests a preference towards lysogenic or other “benign” forms of phage infection when the host is stably present at high abundance.

Conclusion

Long-term persistence of bacteriophage and host could result from mutually beneficial mechanisms driving bacterial strain-level diversity and phage survival in complex environments.
Genes underlying the evolution of tetrapod testes size
Authors: Baker Joanna , Meade Andrew , Venditti Chris
Published: August 2021

Background

Testes vary widely in mass relative to body mass across species, but we know very little about which genes underlie and contribute to such variation. This is partly because evidence for which genes are implicated in testis size variation tends to come from investigations involving just one or a few species. Contemporary comparative phylogenetic methods provide an opportunity to test candidate genes for their role in phenotypic change at a macro-evolutionary scale—across species and over millions of years. Previous attempts to detect genotype-phenotype associations across species have been limited in that they can only detect where genes have driven directional selection (e.g. brain size increase).

Results

Here, we introduce an approach that uses rates of evolutionary change to overcome this limitation to test whether any of twelve candidate genes have driven testis size evolution across tetrapod vertebrates—regardless of directionality. We do this by seeking a relationship between the rates of genetic and phenotypic evolution. Our results reveal five genes (Alkbh5, Dmrtb1, Pld6, Nlrp3, Sp4) that each have played unique and complex roles in tetrapod testis size diversity. In all five genes, we find strong significant associations between the rate of protein-coding substitutions and the rate of testis size evolution. Such an association has never, to our knowledge, been tested before for any gene or phenotype.

Conclusions

We describe a new approach to tackle one of the most fundamental questions in biology: how do individual genes give rise to biological diversity? The ability to detect genotype-phenotype associations that have acted across species has the potential to build a picture of how natural selection has sculpted phenotypic change over millions of years.
Production of neoagarooligosaccharides by probiotic yeast Saccharomyces cerevisiae var. boulardii engineered as a microbial cell factory
Authors: Jin Yerin , Yu Sora , Liu Jing-Jing , Yun Eun Ju , Lee Jae Won , Jin Yong-Su , Kim Kyoung Heon
Published: August 2021

Background

Saccharomyces cerevisiae var. boulardii is a representative probiotic yeast that has been widely used in the food and pharmaceutical industries. However, S. boulardii has not been studied as a microbial cell factory for producing useful substances. Agarose, a major component of red macroalgae, can be depolymerized into neoagarooligosaccharides (NAOSs) by an endo-type β-agarase. NAOSs, including neoagarotetraose (NeoDP4), are known to be health-benefiting substances owing to their prebiotic effect. Thus, NAOS production in the gut is required. In this study, the probiotic yeast S. boulardii was engineered to produce NAOSs by expressing an endo-type β-agarase, BpGH16A, derived from a human gut bacterium Bacteroides plebeius.

Results

In total, four different signal peptides were compared in S. boulardii for protein (BpGH16A) secretion for the first time. The SED1 signal peptide derived from Saccharomyces cerevisiae was selected as optimal for extracellular production of NeoDP4 from agarose. Expression of BpGH16A was performed in two ways using the plasmid vector system and the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system. The production of NeoDP4 by engineered S. boulardii was verified and quantified. NeoDP4 was produced by S. boulardii engineered using the plasmid vector system and CRISPR-Cas9 at 1.86 and 0.80 g/L in a 72-h fermentation, respectively.

Conclusions

This is the first report on NAOS production using the probiotic yeast S. boulardii. Our results suggest that S. boulardii can be considered a microbial cell factory to produce health-beneficial substances in the human gut.

Graphical abstract
Fundamental challenges in assessing the impact of research infrastructure
Authors: Zakaria Sana , Grant Jonathan , Luff Jane
Published: August 2021

Clinical research infrastructure is one of the unsung heroes of the scientific response to the current COVID-19 pandemic. The extensive, long-term funding into research support structures, skilled people, and technology allowed the United Kingdom research response to move off the starting blocks at pace by utilizing pre-existing platforms. The increasing focus from funders on evaluating the outcomes and impact of research infrastructure investment requires both a reframing and progression of the current models in order to address the contribution of the underlying support infrastructure. The majority of current evaluation/outcome models focus on a “pipeline” approach using a methodology which follows the traditional research funding route with the addition of quantitative metrics. These models fail to embrace the complexity caused by the interplay of previous investment, the coalescing of project outputs from different funders, the underlying infrastructure investment, and the parallel development across different parts of the system. Research infrastructure is the underpinning foundation of a project-driven research system and requires long-term, sustained funding and capital investment to maintain scientific and technological expertise. Therefore, the short-term focus on quantitative metrics that are easy to collect and interpret and that can be assessed in a roughly 5-year funding cycle needs to be addressed. The significant level of investment in research infrastructure necessitates investment to develop bespoke methodologies that develop fit-for-purpose, longer-term/continual approach(es) to evaluation. Real-world research should reflect real-world evaluation and allow for the accrual of a narrative of value indicators that build a picture of the contribution of infrastructure to research outcomes. The linear approach is not fit for purpose, the research endeavour is a complex, twisted road, and the evaluation approach needs to embrace this complexity through the development of realist approaches and the rapidly evolving data ecosystem. This paper sets out methodological challenges and considers the need to develop bespoke methodological approaches to allow a richer assessment of impact, contribution, attribution, and evaluation of research infrastructure. This paper is the beginning of a conversation that invites the community to “take up the mantle” and tackle the complexity of real-world research translation and evaluation.
Is the development of obesogenic food environments a self-reinforcing process? Evidence from soft drink consumption
Authors: Ferretti Fabrizio , Mariani Michele , Sarti Elena
Published: August 2021

Background

Understanding how the development of obesogenic food environments and the consumption of ultra-processed foods and beverages influence each other can help policymakers to identify effective ways to curb the current obesity epidemic. This paper was designed to investigate whether, and to what extent, the consumption of soft drinks and the prevalence of obesity are linked through feedback effects.

Methods

An ecological study design and a simultaneous equation model were used to investigate the existence of a vicious cycle between the consumption of soft drinks and the prevalence of obesity. The analysis was based on a longitudinal dataset covering per capita sales of soft drinks, the age-standardised prevalence rate of obesity and several demographic and socio-economic control variables in a sample of 98 countries worldwide for the period 2005–2019.

Results

Using a Two-Stage Least Squares (2SLS) regression model with fixed effects, we documented a self-reinforcing process that links consumption and obesity. Changes in the spread of obesity were associated with changes in soft drink consumption: a one-unit increase in the age-adjusted prevalence rate of obesity increased consumption by about 2.39 l per person per year. Similarly, as the consumption of soft drinks rose, so did the prevalence of obesity: the age-adjusted rate of obesity increased by 0.07% for every additional litre consumed per capita. Computing the impact multipliers, we found that the outcome of a one-unit decrease in the average price of soft drinks was twofold: a) the prevalence of obesity increased by around 0.17%; and b) consumption increased by around 2.40 l per person, the sum of the increase directly caused by the price reduction (2 l) and the increase due to the interplay between consumption and obesity (0.4 l).

Conclusions

This study has identified a feedback loop between unhealthy habits (i.e. the consumption of soft drinks) and health outcomes (i.e. the prevalence of obesity). This interplay amplifies the impact of any exogenous changes in the determinants of consumption and obesity. These feedback effects should be considered and exploited in planning effective strategies to tackle the burden of obesity and the global epidemic of non-​communicable diseases.
Titanium alloy cannulated screws and biodegradable magnesium alloy bionic cannulated screws for treatment of femoral neck fractures: a finite element analysis
Authors: Ding Kai , Yang Weijie , Zhu Jian , Cheng Xiaodong , Wang Haicheng , Hao Du , Yinuo Song , Zhu Yanbin , Zhang Yingze , Chen Wei , Zhang Qi
Published: August 2021

Background

Cannulated screws (CS) are one of the most widely used treatments for femoral neck fracture, however, associated with high rate of complications. In this study, we designed a new type of cannulated screws called degradable magnesium alloy bionic cannulated screws (DMBCS) and our aim was to compare the biomechanical properties of DMBCS, the traditionally used titanium alloy bionic cannulated screws (TBCS) and titanium alloy cannulated screws (TTCS).

Methods

A proximal femur model was established based on CT data of a lower extremity from a voluntary healthy man. Garden type III femoral neck fracture was constructed and fixed with DMBCS, TBCS, and TTCS, respectively. Biomechanical effect which three type of CS models have on femoral neck fracture was evaluated and compared using von Mises stress distribution and displacement.

Results

In the normal model, the maximum stress value of cortical bone and cancellous bone was 76.18 and 6.82 MPa, and the maximum displacement was 5.52 mm. Under 3 different fracture healing status, the stress peak value of the cortical bone and cancellous bone in the DMBCS fixation model was lower than that in the TTCS and TBCS fixation, while the maximum displacement of DMBCS fixation model was slightly higher than that of TTCS and TBCS fixation models. As the fracture heals, stress peak value of the screws and cortical bone of intact models are decreasing, while stress peak value of cancellous bone is increasing initially and then decreasing.

Conclusions

The DMBCS exhibits the superior biomechanical performance than TTCS and TBCS, whose fixation model is closest to the normal model in stress distribution. DMBCS is expected to reduce the rates of post-operative complications with traditional internal fixation and provide practical guidance for the structural design of CS for clinical applications.
DNA methylation patterns at and beyond the histological margin of early-stage invasive lung adenocarcinoma radiologically manifested as pure ground-glass opacity
Authors: Jia Ziqi , Wang Yadong , Xue Jianchao , Yang Xiaoying , Bing Zhongxing , Guo Chao , Gao Chao , Tian Zhenhuan , Zhang Zhenzhen , Kong Hualei , He Qiye , Su Zhixi , Liu Yiying , Song Yang , Liang Dianjing , Liang Naixin , Li Shanqing , Gao Yuan
Published: August 2021

Background

Early-stage lung cancers radiologically manifested as ground-glass opacities (GGOs) have been increasingly identified, among which pure GGO (pGGO) has a good prognosis after local resection. However, the optimal surgical margin is still under debate. Precancerous lesions exist in tumor-adjacent tissues beyond the histological margin. However, potential precancerous epigenetic variation patterns beyond the histological margin of pGGO are yet to be discovered and described.

Results

A genome-wide high-resolution DNA methylation analysis was performed on samples collected from 15 pGGO at tumor core (TC), tumor edge (TE), para-tumor tissues at the 5 mm, 10 mm, 15 mm, 20 mm beyond the tumor, and peripheral normal (PN) tissue. TC and TE were tested with the same genetic alterations, which were also observed in histologically normal tissue at 5 mm in two patients with lower mutation allele frequency. According to the difference of methylation profiles between PN samples, 2284 methylation haplotype blocks (MHBs), 1657 differentially methylated CpG sites (DMCs), and 713 differentially methylated regions (DMRs) were identified using reduced representation bisulfite sequencing (RRBS). Two different patterns of methylation markers were observed: Steep (S) markers sharply changed at 5 mm beyond the histological margin, and Gradual (G) markers changed gradually from TC to PN. S markers composed 86.2% of the tumor-related methylation markers, and G markers composed the other 13.8%. S-marker-associated genes enriched in GO terms that were related to the hallmarks of cancer, and G-markers-associated genes enriched in pathways of stem cell pluripotency and transcriptional misregulation in cancer. Significant difference in DNA methylation score was observed between peripheral normal tissue and tumor-adjacent tissues 5 mm further from the histological margin (p < 0.001 in MHB markers). DNA methylation score at and beyond 10 mm from histological margin is not significantly different from peripheral normal tissues (p > 0.05 in all markers).

Conclusions

According to the methylation pattern observed in our study, it was implied that methylation alterations were not significantly different between tissues at or beyond P10 and distal normal tissues. This finding explained for the excellent prognosis from radical resections with surgical margins of more than 15 mm. The inclusion of epigenetic characteristics into surgical margin analysis may yield a more sensitive and accurate assessment of remnant cancerous and precancerous cells in the surgical margins.
Beta-lactamase-negative ampicillin-resistant Haemophilus influenzae type b meningitis in partially immunized immunocompetent child: a case report
Authors: Qureshi Majid Ali , Asad Imran , Chaudhary Adeel , Abuhammour Walid
Published: August 2021

Introduction

Haemophilus influenzae is a Gram-negative coccobacillus that can cause many different kinds of infection, ranging from mild ear infection to life-threatening diseases like epiglottitis and meningitis. Encapsulated type b Haemophilus influenzae was most commonly responsible for Haemophilus influenzae meningitis in children before introduction of Haemophilus influenzae conjugate vaccine. None or partially immunized children are acquiring meningitis owing to resistant strains of Haemophilus influenzae, namely beta-lactamase-negative ampicillin-resistant strain.

Case presentation

We reported the case of a 2-year-old Emirati boy who presented to our emergency department with fever, diarrhea, vomiting, and fluctuating levels of consciousness. He was developmentally normal with no significant past medical history, except he was partially immunized. Earlier, he had been treated for acute gastroenteritis with intravenous fluids and antiemetics in another hospital and was discharged. His parents escorted him to our emergency department as he became very drowsy. Examination revealed that he was in septic shock. He was immediately treated with oxygen, intravenous antibiotics, and fluids after performing septic workup. He was then shifted to intensive care unit. Blood culture and cerebrospinal fluid Gram stain confirmed diagnosis of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. He was started on intravenous ceftriaxone, acyclovir, and dexamethasone. He still spiked fever after 1 week. Therefore, ceftriaxone was replaced by meropenem. He recovered well with no sequelae.

Conclusion

This case highlights atypical presentation of life-threatening illness along with microbial resistance that had positive outcome due to timely diagnosis and aggressive management by a multidisciplinary team.
A novel RIP1/RIP3 dual inhibitor promoted OPC survival and myelination in a rat neonatal white matter injury model with hOPC graft
Authors: Zhang Chu , Guan Qian , Shi Hao , Cao Lingsheng , Liu Jing , Gao Zixuan , Zhu Wenxi , Yang Yinxiang , Luan Zuo , Yao Ruiqin
Published: August 2021

Background

The dual inhibitors of receptor interacting protein kinase-1 and -3 (RIP1 and RIP3) play an important role in cell death processes and inflammatory responses. White matter injury (WMI), a leading cause of neurodevelopmental disabilities in preterm infants, which is characterized by extensive myelination disturbances and demyelination. Neuroinflammation, leads to the loss and differentiation-inhibition of oligodendrocyte precursor cells (OPCs), represents a major barrier to myelin repair. Whether the novel RIP1/RIP3 dual inhibitor ZJU-37 can promote transplanted OPCs derived from human neural stem cells (hOPCs) survival, differentiation and myelination remains unclear. In this study, we investigated the effect of ZJU-37 on myelination and neurobehavioral function in a neonatal rat WMI model induced by hypoxia and ischemia.

Methods

In vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia, and then treated with ZJU-37 or/and hOPCs, then OPCs apoptosis, myelination, glial cell and NLRP3 inflammasome activation together with cognitive outcome were evaluated at 12 weeks after transplantation. In vitro, the effect of ZJU-37 on NLRP3 inflammasome activation in astrocytes induced by oxygen–glucose deprivation (OGD) were examined by western blot and immunofluorescence. The effect of ZJU-37 on OPCs apoptosis induced by the conditioned medium from OGD-injured astrocytes (OGD-astrocyte-CM) was analyzed by flow cytometry and immunofluorescence.

Results

ZJU-37 combined with hOPCs more effectively decreased OPC apoptosis, promoted myelination in the corpus callosum and improved behavioral function compared to ZJU-37 or hOPCs treatment. In addition, the activation of glial cells and NLRP3 inflammasome was reduced by ZJU-37 or/and hOPCs treatment in the neonatal rat WMI model. In vitro, it was also confirmed that ZJU-37 can suppress NLRP3 inflammasome activation in astrocytes induced by OGD. Not only that, the OGD-astrocyte-CM treated with ZJU-37 obviously attenuated OPC apoptosis and dysdifferentiation caused by the OGD-astrocyte-CM.

Conclusions

The novel RIP1/RIP3 dual inhibitor ZJU-37 may promote OPC survival, differentiation and myelination by inhibiting NLRP3 inflammasome activation in a neonatal rat model of WMI with hOPC graft.
Financial balance of home nursing care providers in the Czech Republic
Authors: Fiala Petr , Holmerova Iva , Ruda Tomas , Steffl Michal
Published: August 2021

Background

To enable people to live in old age in their own homes often requires specialised home care services. Despite the high importance of these services, the finance of home nursing care (HNC) is still under-investigated in many countries. The aim of this paper was to describe the finance of HNC in the Czech Republic.

Methods

Balancing of revenues and costs was done using structured questionnaires from the closed accounting year 2018 as a monthly average. Nonparametric Kruskal-Wallis and Wilcoxon signed ranks tests were used to test hypotheses.

Results

Data from 62 providers were analysed. The data included information from a total of 2297 patients and 995 employees. The average of total costs were € 17,591.7 (95% CI 14,175.3 - 21,008.1) and average of total revenues were € 17,276.5 (95% CI 13,923.5 - 20,629.5). The average cost per a patient was € 516.0 (95% CI 465.9–566.1) and the average revenues were € 500.1 (95% CI 457.0–543.3).

Conclusions

The overall financial balance of HNC providers seems to be balanced in the Czech Republic. Nevertheless, insurance, although it should, did not cover all the costs. Micro- providers tended to be cheaper regarding the hours worked by nurses.
Oxygen reserve index for non-invasive early hypoxemia detection during endotracheal intubation in intensive care: the prospective observational NESOI study
Authors: Hille Hugo , Le Thuaut Aurelie , Canet Emmanuel , Lemarie Jeremie , Crosby Laura , Ottavy Gregoire , Garret Charlotte , Martin Maelle , Seguin Amelie , Lamouche-Wilquin Pauline , Morin Jean , Zambon Olivier , Miaihle Arnaud-Felix , Reignier Jean , Lascarrou Jean-Baptiste
Published: August 2021

Background

To evaluate the ability of the oxygen reserve index (ORI) to predict the occurrence of mild hypoxemia (defined as SpO2  <  97%) during endotracheal intubation (ETI) of patients in the intensive care unit (ICU).

Methods

This observational single-centre study included patients without hypoxemia (defined as SpO2/FiO2  >  214) who required ETI in the ICU. Patients were followed during preoxygenation and ETI then until hospital discharge and/or day 28. We recorded cases of mild hypoxemia, moderate (SpO2  <  90%) and severe (SpO2  <  80%) hypoxemia, moderate arterial hypotension (systolic arterial pressure  <  90 mmHg), oesophageal intubation, aspiration, cardiac arrest, and death.

Results

Between January 2019 and July 2020, 56 patients were included prospectively and 51 patients were analysed. Twenty patients had mild hypoxemia between the end of preoxygenation and the end of intubation; in 10 of these patients, the decrease in SpO2 below 97% was preceded by an ORI  <  0.4, the median time difference being 81 s [interquartile range, 34–146]. By multivariable analysis, a higher ORI (by 0.1 increase) value during preoxygenation was associated with absence of hypoxemia (odds ratio, 0.76; 95% confidence interval, 0.61;0.95; P  =  0.0141).

Conclusion

In non-hypoxemic patients, the 81-s [34–146] median time between the ORI decrease below 0.4 and the SpO2 decrease below 97% during apnoea may allow preventive action. A higher ORI value during preoxygenation was independently protective against hypoxemia. Whether these findings also apply to hypoxemic patients, and the clinical impact of a preoxygenation strategy based on ORI monitoring, remain to be evaluated prospectively.

Trial Registration ClinicalTrial.gov, #NCT03600181.
Enrollment, retention, and strategies for including disadvantaged populations in randomized controlled trials: a systematic review protocol
Authors: LaPlante Abigail , Yen Renata W. , Isaacs Talia , Crocker Joanna , Demjen Zsofia , Schubbe Danielle , Kennedy Alice M. , Engel Jaclyn , O’Brien Nancy , Richters Carla , Durand Marie-Anne
Published: August 2021

Background

Many randomized controlled trials fail to reach their target sample size. When coupled with the omission and underrepresentation of disadvantaged groups in randomized controlled trials, many trials fail to obtain data that accurately represents the true diversity of their target population. Policies and practices have been implemented to increase representation of disadvantaged groups in many randomized controlled trials, with some trials specifically targeting such groups. To our knowledge, no systematic review has quantified the enrollment metrics and effectiveness of inclusion and retention strategies in randomized controlled trials focused on disadvantaged populations specifically.

Methods

We will conduct a systematic search across EMBASE, MEDLINE, Web of Science, and CINAHL as well as grey literature, conference proceedings, research monographs, and Google Scholar from inception onwards. We will include randomized controlled trials where at least 50% of enrolled participants are considered to be disadvantaged, as per the RCT authors’ definition and in line with our inclusion criteria. Two independent researchers per article will conduct preliminary title and abstract screening, subsequent full text review, and data extraction for the selected trials, with a third reviewer available to resolve conflicts. We will assess the quality of all included studies using specific criteria regarding data reporting, external validity, and internal validity. We will combine all selected studies and conduct a narrative synthesis to assess enrollment metrics. If there is sufficient homogeneity and sufficient trials comparing recruitment strategies within disadvantaged populations, we will conduct a random effects meta-analysis to evaluate the effectiveness of strategies designed to maximize the inclusion of disadvantaged populations in randomized controlled trials.

Discussion

The findings of this systematic review will establish baseline recruitment and enrollment metrics of trials targeting disadvantaged populations to elucidate the scope of the challenge of recruiting such populations. We hope that our findings will promote future research on the distinct barriers that may prevent disadvantaged populations from participating in health intervention research, will encourage more trials exploring effective, tailored recruitment strategies, and will establish a foundation to track future progress in the recruitment of disadvantaged populations.

Trial registrations

PROSPERO ID: CRD42020152814
Advanced glycosylation end products inhibit the proliferation of bone-marrow stromal cells through activating MAPK pathway
Authors: Li Zheng , Wang Xiao , Hong Tian-pei , Wang Hao-jie , Gao Zhan-yi , Wan Meng
Published: August 2021

Background

The purpose of present study was to explore the mechanism of nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B(PKB/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways after intervention of advanced glycosylation end products (AGEs) on rat bone-marrow stromal cells (BMSCs).

Methods

Prepare and identify AGEs. BMSCs were isolated from 16 SD rats and cultured with different concentration of AGEs. Cell viability was detected by cell counting kit-8 (CCK-8). BMSCs were cultured with AGEs (0.25 mg/ml) for 30 min, 12 h, 24 h, 72 h and 120 h. In addition, BMSCs were cultured with AGEs, AGEs + JNK inhibitor and AGEs + P38 inhibitor for 24 h and 48 h, respectively. Western blotting and RT-PCR were used to determine the protein and mRNA expression levels, respectively.

Results

Cell viability of BMSCs was significantly correlated with concentration and effect time of AGEs (P < 0.05), and the most appropriate concentration was 0.25 mg/ml. AGEs stimulation significantly increased the protein expression levels of NF-κB p65, JNK, p38 (P < 0.05), decreased IκB (P < 0.05), but had no effect on the protein expression of Akt in BMSCs (P > 0.05). At the mRNA level, JNK and p38 inhibitors significantly reduced the levels of NF-κB p65, p38 and JNK, increased IκB (P > 0.05), but had no effect on Akt in BMSCs (P > 0.05). At the protein level, JNK and p38 inhibitors notably decreased the expression of NF-κB p65, p38, p-JNK, P-IκB and JNK (P < 0.001), and increased IκB (P < 0.05).

Conclusion

Advanced glycosylation end products can inhibit the proliferation of bone-marrow stromal cells through activating MAPK pathway.
Perception of personalized medicine, pharmacogenomics, and genetic testing among undergraduates in Hong Kong
Authors: Cheung Nicholas Yan Chai , Fung Jasmine Lee Fong , Ng Yvette Nga Chung , Wong Wilfred Hing Sang , Chung Claudia Ching Yan , Mak Christopher Chun Yu , Chung Brian Hon Yin
Published: August 2021

Background

The global development and advancement of genomic medicine in the recent decade has accelerated the implementation of personalized medicine (PM) and pharmacogenomics (PGx) into clinical practice, while catalyzing the emergence of genetic testing (GT) with relevant ethical, legal, and social implications (ELSI).

Results

The perception of university undergraduates with regards to PM and PGx was investigated, and 80% of undergraduates valued PM as a promising healthcare model with 66% indicating awareness of personal genome testing companies. When asked about the curriculum design towards PM and PGx, compared to undergraduates in non-medically related curriculum, those studying in medically related curriculum had an adjusted 7.2 odds of perceiving that their curriculum was well-designed for learning PGx (95% CI 3.6–14.6) and a 3.7 odds of perceiving that PGx was important in their study (95% CI 2.0–6.8). Despite this, only 16% of medically related curriculum undergraduates would consider embarking on future education on PM.

When asked about their perceptions on GT, 60% rated their genetic knowledge as “School Biology” level or below while 76% would consider undergoing a genetic test. As for ELSI, 75% of undergraduates perceived that they were aware of ethical issues of GT in general, particularly on “Patient Privacy” (80%) and “Data Confidentiality” (68%).

Undergraduates were also asked about their perceived reaction upon receiving an unfavorable result from GT, and over half of the participants perceived that they would feel “helpless or pessimistic” (56%), “inadequate or different” (59%), and “disadvantaged at job seeking” (59%), while older undergraduates had an adjusted 2.0 odds of holding the latter opinion (95% CI 1.1–3.5), compared to younger undergraduates.

Conclusion

Hong Kong undergraduates showed a high awareness of PM but insufficient genetic knowledge and low interest in pursuing a career towards PM. They were generally aware of ethical issues of GT and especially concerned about patient privacy and data confidentiality. There was a predominance of pessimistic views towards unfavorable testing results. This study calls for the attention to evaluate education and talent development on genomics, and update existing legal frameworks on genetic testing in Hong Kong.
Evaluation of Cr(VI) adsorption on glutaraldehyde crosslinked chitosan beads using cyclic voltammetry employing gold electrode
Authors: Watwe Varuna , Kulkarni Preeti
Published: August 2021

Hexavalent chromium is one of the toxic heavy metals found in wastewaters from industries like electroplating, leather tanning, and steel manufacturing. The Cr(VI) removal and quantitative detection are among the major concerns from an environmental toxicity point of view. In the present work, we report an effective electrochemical technique for Cr(VI) monitoring based on the utilization of gold electrode. The technique developed is user-friendly, non-destructive, and provides real-time monitoring of Cr(VI) from wastewaters in contrast to other spectroscopic and optical techniques. The technique developed was applied in monitoring Cr(VI) removal from synthetic Cr(VI) samples using chitosan cross-linked glutaraldehyde (C + G) beads. The parameter optimization for Cr(VI) removal using C + G beads was done. The experimental data of Cr(VI) adsorption on C + G beads obtained using cyclic voltammetry were further used for kinetic and thermodynamic studies. Kinetic and thermodynamic studies found that Cr(VI) adsorption follows pseudo-second-order kinetics and Modified Langmuir isotherm. The maximum adsorption capacity of C + G beads for Cr(VI) was found to be 28.65 mg g−1. These results obtained indicate that the cyclic voltammetric technique using gold electrode can be effectively applied for Cr(VI) analysis from wastewaters.
Progression of pelvic retroversion is a critical factor for clinical outcome after Opening-wedge high tibial osteotomy among elderly patients
Authors: Otsuki Shuhei , Wakama Hitoshi , Ikeda Kuniaki , Okuno Nobuhiro , Okamoto Yoshinori , Okayoshi Tomohiro , Matsuyama Junya , Neo Masashi
Published: August 2021

Purpose

To evaluate the clinical outcome after opening-wedge high tibial osteotomy (OWHTO) and to determine the critical factors for a poor clinical outcome after OWHTO in patients aged over 65 years.

Methods

Our retrospective analysis was based on the data from 233 patients who underwent OWHTO for medial compartment knee OA at our institution between January 2013 and December 2018, and 88 patients (36 men and 52 women) over 65 years of age were included in this study. Radiographic parameters of weight-bearing line ratio (WBLR) and pelvic inclination (PI); the knee function, range of motion (ROM) and extension; and clinical outcome with Lysholm score were obtained preoperatively and postoperatively at the final follow-up visit. To evaluate the critical factors for the clinical outcome, univariate regression analysis was used to identify the relationship between postoperative and improved Lysholm score and pre-and post-operative essential factors. To reveal the factor having a greater impact on the clinical outcome, ap < 0.05 in univariate factors was entered into a multivariate regression analysis.

Results

The preoperative WBLR was significantly changed, and Lysholm score improved from 59.5 to 81.5 (p < 0.0001), whereas the PI, knee extension and ROM were not changed after OWHTO. Regarding the essential factors affecting clinical outcome after OWHTO, age and delta PI were negative, whereas preoperative WBLR, postoperative ROM, especially extension, had a positive effect (p < 0.05). Furthermore, only delta PI had affected the improvement of clinical outcome with OWHTO (p < 0.01), and postoperative knee extension was negatively correlated with the progression of pelvic retroversion (p < 0.01).

Conclusion

Age at surgery and progression of pelvic retroversion were the critical factors for poor postoperative clinical outcomes after OWHTO. Care should be taken for the progression of pelvic retroversion after OWHTO because it deteriorates the clinical outcome by inducing the knee flexion contracture as the compensatory mechanism for the balance of sagittal alignment.
Cutaneous metastasis of cecum cancer with MSI-high and BRAFV600E mutation: a case report
Authors: Yunoki Kosuke , Yano Takuya , Yoshimitsu Masanori , Oshita Ko , Kubota Tetsushi , Ishida Michihiro , Satoh Daisuke , Choda Yasuhiro , Nakano Kanyu , Shirakawa Yasuhiro , Matsukawa Hiroyoshi , Idani Hitoshi , Shiozaki Shigehiro , Okajima Masazumi
Published: August 2021

Background

Cutaneous metastases of colorectal cancer (CRC) are rare, occurring in 0.7% to 5% of cancer patients. Furthermore, the molecular subtypes of cutaneous metastasis of CRC are unclear. Here, we present a rare case of cutaneous metastasis of high-frequency microsatellite instability (MSI-high)/BRAFV600E-mutant cecum cancer.

Case presentation

A 77-year-old woman presented at the outpatient clinic with a subcutaneous mass on her left back. An excisional biopsy was performed and metastatic cutaneous adenocarcinoma was diagnosed. A computed tomography scan of the thorax and abdomen showed thickening of the cecum wall, the presence of pericolic lymph nodes, multiple masses in the liver, and a single nodule in the right lung. Right colectomy with D2 lymphadenectomy and functional end-to-end anastomosis was performed because of the almost-complete intestinal obstruction. The expression of KRAS wild type, BRAFV600E mutation, and MSI-high was detected in the cecum cancer using molecular pathological examination. She received chemotherapy with XELOX + BEV regimen (capecitabine + oxaliplatin + bevacizumab). After four administrations, a computed tomography scan showed reduction of distant metastases, which suggested partial response.

Conclusions

We encountered a rare case of cutaneous metastasis of MSI-high and BRAFV600E-mutant cecum cancer. In the future, it will be necessary to accumulate more cases to identify clinical features and more effective treatments for CRCs with cutaneous metastasis.
Intraocular lens power calculation formulas accuracy in combined phacovitrectomy: an 8-formulas comparison study
Authors: Hipólito-Fernandes Diogo , Elisa Luís Maria , Maleita Diogo , Gil Pedro , Maduro Vitor , Costa Lívio , Marques Nuno , Branco João , Alves Nuno
Published: August 2021

Background

Our study aimed to assess and compare the accuracy of 8 intraocular lens (IOL) power calculation formulas (Barrett Universal II, EVO 2.0, Haigis, Hoffer Q, Holladay 1, Kane and PEARL-DGS) in patients submitted to combined phacovitrectomy for vitreomacular (VM) interface disorders.

Methods

Retrospective chart review study including axial-length matched patients submitted to phacoemulsification alone (Group 1) and combined phacovitrectomy (Group 2). Using optimized constants in both groups, refraction prediction error of each formula was calculated for each eye. The optimised constants from Group 1 were also applied to patients of Group 2 – Group 3. Outcome measures included the mean prediction error (ME) and its standard deviation (SD), mean (MAE) and median (MedAE) absolute errors, in diopters (D), and the percentage of eyes within ± 0.25D, ± 0.50D and ± 1.00D.

Results

A total of 220 eyes were included (Group 1: 100; Group 2: 120). In Group 1, the difference in formulas absolute error was significative (p = 0.005). The Kane Formula had the lowest MAE (0.306) and MedAE (0.264). In Group 2, Kane had the overall best performance, followed by PEARL-DGS, EVO 2.0 and Barrett Universal II. The ME of all formulas in both Groups 1 and 2 were 0.000 (p = 0.934; p = 0.971, respectively). In Group 3, a statistically significant myopic shift was observed for each formula (p < 0.001).

Conclusion

Surgeons must be careful regarding IOL power selection in phacovitrectomy considering the systematic myopic shift evidenced—constant optimization may help eliminating such error. Moreover, newly introduced formulas and calculation methods may help us achieving increasingly better refractive outcomes both in cataract surgery alone and phacovitrectomy.
High dose letrozole in infertile women with unilateral tubal block: a preliminary report
Authors: Al-Hussaini Tarek K.
Published: August 2021

Background

Till now, there is no universal agreement on the best management of women with unilateral blocked tube. The aim of this study was to evaluate the use of high dose letrozole in infertile women with one blocked tube. This prospective non-randomized study was conducted at a university-affiliated infertility unit. It included 15 women with one blocked tube (proximal or mid segmental block) with a period of 1–6 years of infertility. Letrozole (10 mg/day for 5 days) was prescribed for all of them for a maximum of three cycles. The primary outcome was Live birth rate.

Results

Nine out of the 15 women conceived (60%). Live birth rate was 53% (8/15). All women had a good response to this regimen. None complained of side effects of this dose. No multiple pregnancies and/or congenital anomalies were reported.

Conclusions

This preliminary report showed that treatment of infertile women, with unilateral tubal block, with high dose letrozole is effective. To our knowledge, this is the first report in the English literature on the use of high dose of letrozole in such cases.
Patient-Reported Outcomes Integrated Within an Electronic Medical Record in Patients With Head and Neck Cancer
Authors: Ossowski Stephanie , Kammerer Amy , Stram Douglas , Piazza-DeLap Lisa , Basch Ethan , Katzel Jed A.
Published: August 2021

PURPOSE

Patient-reported outcome (PRO) tools lead to clinical benefits, including improved overall survival for patients with cancer. However, routine implementation of PROs in clinical practice within the electronic medical record (EMR) by integrated health care delivery systems remains limited. We studied the use of a PRO tool for patients with head and neck cancer (HNC) integrated in an EMR at Kaiser Permanente in Northern California.

METHODS

Between August 2017 and December 2019, patients with newly diagnosed HNC were surveyed at baseline, then every 3 months using the Functional Assessment of Cancer Therapy–General 7 and Functional Assessment of Cancer Therapy–Head and Neck (version 4). A medical assistant performed a baseline survey on diagnosis and then notified patients electronically per surveillance protocol. Patients who did not respond to online PRO surveys could complete them via telephone or in-person appointments with medical assistants. Abnormal findings on PRO surveys were referred to appropriate members of the care team or the treating Otolaryngology-Head and Neck Surgery physicians.

RESULTS

Two hundred ninety patients received baseline surveys. Patients received up to a maximum of eight subsequent surveys. Of a total of 597 electronic surveys, 585 (97.9%) were completed. The percentage of patients completing each interval survey ranged from 92% to 100%. Multivariate Poisson regression analysis showed patients with English as their primary language and an online secure account were the most likely to complete surveys compared with those patients with non-English as a primary language and without an online account.

CONCLUSION

PRO tools can be effectively used within the EMR for patients with HNC with a high response rate provided there is strong engagement from a dedicated member of the care team. This has important implications for designing clinical trials and symptom monitoring in clinical practices that incorporate EMRs.
Immunotherapy in Patients With Locally Advanced Esophageal Carcinoma: ASCO Treatment of Locally Advanced Esophageal Carcinoma Guideline Rapid Recommendation Update
Authors: Shah Manish A. , Hofstetter Wayne L. , Kennedy Erin B. ,   for the Locally Advanced Esophageal Carcinoma Guideline Expert Panel
Published: August 2021

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
Teleoncology for Veterans: High Patient Satisfaction Coupled With Positive Financial and Environmental Impacts
Authors: Jiang Cindy Y. , Strohbehn Garth W. , Dedinsky Rachel M. , Raupp Shelby M. , Pannecouk Brittany M. , Yentz Sarah E. , Ramnath Nithya
Published: August 2021

PURPOSE:

There was rapid adoption of teleoncology care in the Veterans Health Administration during the COVID-19 pandemic. One third of 9 million Veterans Health Administration enrolled Veterans live in rural areas. Although digital solutions can expand capacity, enhance care access, and reduce financial burden, they may also exacerbate rural-urban health disparities. Careful evaluation of patients' perceptions and policy tradeoffs are necessary to optimize teleoncology postpandemic.

METHODS:

Patients with ≥ 1 teleoncology visit with medical, surgical, or radiation oncology between March 2020 and June 2020 were identified retrospectively. Validated, Likert-type survey assessing patient satisfaction was developed. Follow-up survey was conducted on patients with ≥ 1 teleoncology visit from August 2020 to January 2021. Travel distance, time, cost, and carbon dioxide emissions were calculated based on zip codes.

RESULTS:

A hundred surveys were completed (response rate, 62%). Patients overall were satisfied with teleoncology (83% Agree or Strongly Agree) but felt less satisfied than in-person visits (47% Agree or Strongly Agree). Audiovisual component improved patient perception of involvement in care, ability to self-manage health or medical needs, and comparability to in-person visits. Follow-up survey demonstrated similar satisfaction. Total travel-related savings are as follows: 86,470 miles, 84,374 minutes, $49,720 US dollars, and 35.5 metric tons of carbon dioxide.

CONCLUSION:

Veterans are broadly satisfied with teleoncology. Audiovisual capabilities are critical to satisfaction. This is challenging for rural populations with lack of technology access. Patients experienced financial and time savings, and society benefitted from reduced carbon emissions. Continued optimization is needed to enhance patient experience and address secondary effects.