bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and risk factors for trocar-site incisional hernia detected by clinical and ultrasound examination: a prospective observational study
Authors: Ciscar Ana , Badia Josep M. , Novell Francesc , Bolívar Santiago , Mans Esther
Published: December 2020

Background

Trocar site incisional hernia (TSIH) is the most frequent complication associated with laparoscopic surgery. Few studies currently describe its incidence or risk factors. The aim of this report is to determine the real incidence of TSIH and to identify risk factors.

Methods

A cross-sectional prospective study was performed including consecutive patients who underwent a laparoscopic procedure during a 4 months period. All the patients were assessed both clinically (TSIHc) and by an ultrasonographic examination (TSIHu). The main variable studied was the incidence of TSIH. A multivariate analysis was performed to identify risk factors.

Results

76 patients were included. 27.6% of patients were clinically diagnosed as having TSIH (TSIHc) but only 23.7% of those cases were radiologically confirmed (TSIHu). In the logistic regression analysis, age > 70 years (OR 3.462 CI 1.14–10.515, p = 0.028) and body mass index (BMI) ≥ 30 kg/m2 (OR 3.313 CI 1.037–10.588, p = 0.043) were identified as risk factors for TSIH. The size of the trocar also showed statistically significant differences (p < 0.001). Mean follow-up time was 34 months.

Conclusions

TSIH is under-diagnosed due to the lack of related symptomatology and the inadequacy of the postoperative follow-up period. We detected discrepancies between the clinical and ultrasonographic examinations. TSIHu should be considered as the gold standard for the diagnosis of TSIH. Risk factors such as age, BMI and size of the trocar were confirmed. Patients should be followed-up for a minimum of 2 years.

Trial registration The study has been retrospectively registered in Clinicaltrials.gov on June 4, 2020 under registration number: NCT04410744
Bacillus sp. CSK2 produced thermostable alkaline keratinase using agro-wastes: keratinolytic enzyme characterization
Authors: Nnolim Nonso E. , Nwodo Uchechukwu U.
Published: December 2020

Background

Chicken feathers are the most abundant agro-wastes emanating from the poultry processing farms and present major concerns to environmentalists. Bioutilization of intractable feather wastes for the production of critical proteolytic enzymes is highly attractive from both ecological and biotechnological perspectives. Consequently, physicochemical conditions influencing keratinase production by Bacillus sp. CSK2 on chicken feathers formulation was optimized, and the keratinase was characterized.

Results

The highest enzyme activity of 1539.09 ± 68.14 U/mL was obtained after 48 h of incubation with optimized conditions consisting of chicken feathers (7.5 g/L), maltose (2.0 g/L), initial fermentation pH (5.0), incubation temperature (30 °C), and agitation speed (200 rpm). The keratinase showed optimal catalytic efficiency at pH 8.0 and a temperature range of 60 °C – 80 °C. The keratinase thermostability was remarkable with a half-life of above 120 min at 70 °C. Keratinase catalytic efficiency was halted by ethylenediaminetetraacetic acid and 1,10-phenanthroline. However, keratinase activity was enhanced by 2-mercaptoethanol, dimethyl sulfoxide, tween-80, but was strongly inhibited by Al3+ and Fe3+. Upon treatment with laundry detergents, the following keratinase residual activities were achieved: 85.19 ± 1.33% (Sunlight), 90.33 ± 5.95% (Surf), 80.16 ± 2.99% (Omo), 99.49 ± 3.11% (Ariel), and 87.19 ± 0.26% (Maq).

Conclusion

The remarkable stability of the keratinase with an admixture of organic solvents or laundry detergents portends the industrial and biotechnological significance of the biocatalyst.
Sexually transmitted infections related care-seeking behavior and associated factors among reproductive age women in Ethiopia: further analysis of the 2016 demographic and health survey
Authors: Handebo Simegnew
Published: December 2020

Background

Sexually transmitted infections (STIs) are the most common communicable diseases that affect the health and life of people. Even though there is little information on the prevalence of STIs in Ethiopia, the problem is likely similar to other developing countries. Therefore, the objective of this study was to measure STIs related care-seeking behavior and associated factors among reproductive-age women in Ethiopia.

Methods

The study was based on the data from the 2016 Ethiopian Demographic and Health Survey (EDHS). Information on STIs related care-seeking was extracted from the individual women dataset. A total of 474 (weighted) reproductive age women (15–49 years) who reported STIs or STI symptoms were included in the study. Bivariate and multivariable logistic regression models were fitted to assess factors associated with STIs related care-seeking behavior. The adjusted odds ratio (AOR) with the corresponding 95% confidence intervals (CI) was used to show the strength of associations between the outcome and independent variables. Variables with a p value of less than 0.05 were considered statistically significant.

Results

The prevalence of STIs related care-seeking behavior among women was 33.3% (95% CI 29.2–37.3%). STIs related care-seeking behavior was significantly associated with higher women educational status (AOR = 0.16, 95% CI 0.03, 0.87), having a husband working an unskilled job (AOR = 6.99, 95% CI 1.34, 36.48), women who did not know their husband’s job (AOR = 12.79, 95% CI 2.24, 73.11), having an educated husband (AOR = 5.66, 95% CI 1.36, 23.51), being currently pregnant (AOR = 4.87, 95% CI 1.93, 12.28), being in the richer (AOR = 4.68, 95% CI 1.52, 14.39) and richest (AOR = 6.89, 95% CI 1.90, 24.81) wealth index.

Conclusion

STIs related care-seeking behavior was significantly low among Ethiopian women. Surprisingly, STIs related care-seeking behavior was lower among an educated woman. In contrast, having an educated husband, women who didn’t know their husband’s job, a husband working an unskilled job, being pregnant, and high wealth status were positively associated with STIs related care-seeking behavior.
Conversational ontology operator: patient-centric vaccine dialogue management engine for spoken conversational agents
Authors: Amith Muhammad , Lin Rebecca Z. , Cui Licong , Wang Dennis , Zhu Anna , Xiong Grace , Xu Hua , Roberts Kirk , Tao Cui
Published: December 2020

Background

Previously, we introduced our Patient Health Information Dialogue Ontology (PHIDO) that manages the dialogue and contextual information of the session between an agent and a health consumer. In this study, we take the next step and introduce the Conversational Ontology Operator (COO), the software engine harnessing PHIDO. We also developed a question-answering subsystem called Frankenstein Ontology Question-Answering for User-centric Systems (FOQUS) to support the dialogue interaction.

Methods

We tested both the dialogue engine and the question-answering system using application-based competency questions and questions furnished from our previous Wizard of OZ simulation trials.

Results

Our results revealed that the dialogue engine is able to perform the core tasks of communicating health information and conversational flow. Inter-rater agreement and accuracy scores among four reviewers indicated perceived, acceptable responses to the questions asked by participants from the simulation studies, yet the composition of the responses was deemed mediocre by our evaluators.

Conclusions

Overall, we present some preliminary evidence of a functioning ontology-based system to manage dialogue and consumer questions. Future plans for this work will involve deploying this system in a speech-enabled agent to assess its usage with potential health consumer users.
An ontology-based documentation of data discovery and integration process in cancer outcomes research
Authors: Zhang Hansi , Guo Yi , Prosperi Mattia , Bian Jiang
Published: December 2020

Background

To reduce cancer mortality and improve cancer outcomes, it is critical to understand the various cancer risk factors (RFs) across different domains (e.g., genetic, environmental, and behavioral risk factors) and levels (e.g., individual, interpersonal, and community levels). However, prior research on RFs of cancer outcomes, has primarily focused on individual level RFs due to the lack of integrated datasets that contain multi-level, multi-domain RFs. Further, the lack of a consensus and proper guidance on systematically identify RFs also increase the difficulty of RF selection from heterogenous data sources in a multi-level integrative data analysis (mIDA) study. More importantly, as mIDA studies require integrating heterogenous data sources, the data integration processes in the limited number of existing mIDA studies are inconsistently performed and poorly documented, and thus threatening transparency and reproducibility.

Methods

Informed by the National Institute on Minority Health and Health Disparities (NIMHD) research framework, we (1) reviewed existing reporting guidelines from the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network and (2) developed a theory-driven reporting guideline to guide the RF variable selection, data source selection, and data integration process. Then, we developed an ontology to standardize the documentation of the RF selection and data integration process in mIDA studies.

Results

We summarized the review results and created a reporting guideline—ATTEST—for reporting the variable selection and data source selection and integration process. We provided an ATTEST check list to help researchers to annotate and clearly document each step of their mIDA studies to ensure the transparency and reproducibility. We used the ATTEST to report two mIDA case studies and further transformed annotation results into sematic triples, so that the relationships among variables, data sources and integration processes are explicitly standardized and modeled using the classes and properties from OD-ATTEST.

Conclusion

Our ontology-based reporting guideline solves some key challenges in current mIDA studies for cancer outcomes research, through providing (1) a theory-driven guidance for multi-level and multi-domain RF variable and data source selection; and (2) a standardized documentation of the data selection and integration processes powered by an ontology, thus a way to enable sharing of mIDA study reports among researchers.
A deep learning approach for identifying cancer survivors living with post-traumatic stress disorder on Twitter
Authors: Ismail Nur Hafieza , Liu Ninghao , Du Mengnan , He Zhe , Hu Xia
Published: December 2020

Background

Emotions after surviving cancer can be complicated. The survivors may have gained new strength to continue life, but some of them may begin to deal with complicated feelings and emotional stress due to trauma and fear of cancer recurrence. The widespread use of Twitter for socializing has been the alternative medium for data collection compared to traditional studies of mental health, which primarily depend on information taken from medical staff with their consent. These social media data, to a certain extent, reflect the users’ psychological state. However, Twitter also contains a mix of noisy and genuine tweets. The process of manually identifying genuine tweets is expensive and time-consuming.

Methods

We stream the data using cancer as a keyword to filter the tweets with cancer-free and use post-traumatic stress disorder (PTSD) related keywords to reduce the time spent on the annotation task. Convolutional Neural Network (CNN) learns the representations of the input to identify cancer survivors with PTSD.

Results

The results present that the proposed CNN can effectively identify cancer survivors with PTSD. The experiments on real-world datasets show that our model outperforms the baselines and correctly classifies the new tweets.

Conclusions

PTSD is one of the severe anxiety disorders that could affect individuals who are exposed to traumatic events, including cancer. Cancer survivors are at risk of short-term or long-term effects on physical and psycho-social well-being. Therefore, the evaluation and treatment of PTSD are essential parts of cancer survivorship care. It will act as an alarming system by detecting the PTSD presence based on users’ postings on Twitter.
Shared decision making, physicians’ explanations, and treatment satisfaction: a cross-sectional survey of prostate cancer patients
Authors: Nakayama Kazuhiro , Osaka Wakako , Matsubara Nobuaki , Takeuchi Tsutomu , Toyoda Mayumi , Ohtake Noriyuki , Uemura Hiroji
Published: December 2020

Background

Hormone therapy is one option for some types of prostate cancer. Shared decision making (SDM) is important in the decision making process, but SDM between prostate cancer patients receiving hormone therapy and physicians is not fully understood. This study tested hypotheses: “Patients’ perception of SDM is associated with treatment satisfaction, mediated by satisfaction with physicians’ explanations and perceived effective decision making” and “The amount of information provided to patients by physicians on diseases and treatment is associated with treatment satisfaction mediated by patients’ perceived SDM and satisfaction with physicians’ explanations.”

Methods

This cross-sectional study was conducted using an online panel via a private research company in Japan. The participants in this study were patients registered with the panel who had received or were currently receiving hormone therapy for prostate cancer and physicians registered with the panel who were treating patients with prostate cancer. Measures used in this study included a nine-item Shared Decision Making Questionnaire, levels of satisfaction with physicians’ explanations and treatment satisfaction, and effective decision making for patients (feeling the choice is informed, value-based, likely to be implemented and expressing satisfaction with the choice), and a Shared Decision Making Questionnaire for Doctors. The hypotheses were examined using path analysis.

Results

In total, 124 patients and 150 physicians were included in the analyses. In keeping with our hypotheses, perceived SDM significantly correlated with the physicians’ explanations and perceived effective decision making for patients, and satisfaction with physicians’ explanations and perceived effective decision making for patients were both related to treatment satisfaction. Although the amount of information provided to patients was correlated with the perceived SDM, it was indirectly related to their satisfaction with physicians’ explanations.

Conclusions

When physicians encourage patients to be actively involved in making decisions about treatment through the SDM process while presenting a wide range of information at the start of hormone therapy, patients’ effective decision making and physicians’ explanations may be improved; consequently, the patients’ overall treatment satisfaction may be improved. Physicians who treat patients with prostate cancer may have underestimated the importance of SDM before starting hormone therapy, even greater extent than patients.
Patterns and patient factors associated with loss to follow-up in the Muhimbili sickle cell cohort, Tanzania
Authors: Masamu Upendo , Sangeda Raphael Z. , Kandonga Daniel , Ondengo Jesca , Ndobho Flora , Mmbando Bruno , Nkya Siana , Msami Khadija , Makani Julie
Published: December 2020

Background

Monitoring patient’s clinical attendance is a crucial means of improving retention in care and treatment programmes. Sickle cell patients’ outcomes are improved by participation in comprehensive care programmes, but these benefits cannot be achieved when patients are lost from clinical care. In this study, patients are defined as loss to follow-up when they did not attend clinic for more than 9 months. Precise information on the retention rate and characteristics of those who are not following their clinic appointments is needed to enable the implementation of interventions that will be effective in increasing the retention to care.

Method

This was a retrospective study involving sickle cell patients registered in the Muhimbili Sickle Cohort in Tanzania. Descriptive and survival analysis techniques both non-parametric methods (Kaplan-Meier estimator and Log-rank test) and semi-parametric method (Cox’s proportional hazard model), were used. A p-value of 0.05 was considered significant to make an inference from the analysis.

Results

A total of 5476 patients were registered in the cohort from 2004 to 2016. Of these, 3350 (58.13%) were actively participating in clinics, while 2126 (41.87%) were inactive, of which 1927 (35.19%) were loss to follow-up. We used data from 2004 to 2014 because between 2015 and 2016, patients were referred to other government hospitals. From the survival analysis results, pediatric (HR: 14.29,95% CI: 11.0071–18.5768, p <  0.001) and children between 5 and 17 years [HR:2.61,95% CI:2.2324–3.0705, p <  0.001] patients were more likely to be loss to follow-up than the adult (18 and above years) patients. It was found that patients with above averages for hematocrit (HR: 2.38, 95% CI: 1.0076–1.0404, p = 0.0039) or mean cell volume (HR: 4.28, (95% CI: 1.0260–1.0598, p < 0.001) were more likely to be loss to follow-up than their counterparts.

Conclusion

Loss to follow-up is evident in the cohort of patients in long term comprehensive care. It is, therefore, necessary to design interventions that improve patients’ retention. Suggested solutions include refresher training for health care workers and those responsible for patient follow-up on techniques for retaining patients and comprehensive transition programs to prepare patients who are moving from pediatric to adult clinics.
Expression of PAWR predicts prognosis of ovarian cancer
Authors: Tan Jiahong , Tao Kangjia , Zheng Xu , Liu Dan , Ma Ding , Gao Qinglei
Published: December 2020

Background

Ovarian cancer greatly threatens the general health of women worldwide. Implementation of predictive prognostic biomarkers aids in ovarian cancer management.

Methods

Using online databases, the general expression profile, target-disease associations, and interaction network of PAWR were explored. To identify the role of PAWR in ovarian cancer, gene correlation analysis, survival analysis, and combined analysis of drug responsiveness and PAWR expression were performed. The predictive prognostic value of PAWR was further validated in clinical samples.

Results

PAWR was widely expressed in normal and cancer tissues, with decreased expression in ovarian cancer tissues compared with normal tissues. PAWR was associated with various cancers including ovarian cancer. PAWR formed a regulatory network with a group of proteins and correlated with several genes, which were both implicated in ovarian cancer and drug responsiveness. High PAWR expression denoted better survival in ovarian cancer patients (OS: HR = 0.84, P = 0.0077; PFS, HR = 0.86, P = 0.049). Expression of PAWR could predict platinum responsiveness in ovarian cancer and there was a positive correlation between PAWR gene effect and paclitaxel sensitivity. In 12 paired clinical samples, the cancerous tissues exhibited significantly lower PAWR expression than matched normal fallopian tubes. The predictive prognostic value of PAWR was maintained in a cohort of 50 ovarian cancer patients.

Conclusions

High PAWR expression indicated better survival and higher drug responsiveness in ovarian cancer patients. PAWR could be exploited as a predictive prognostic biomarker in ovarian cancer.
Seldom heard voices: a meta-narrative systematic review of Aboriginal and Torres Strait Islander peoples healthcare experiences
Authors: Jones Benjamin , Heslop David , Harrison Reema
Published: December 2020

Background

It is well established that Aboriginal and Torres Strait Islander populations face considerable health inequities, exacerbated by poorer healthcare quality. Patient experience is recognised as a major contributing factor to healthcare quality and outcomes, therefore, enriched knowledge of the patient experiences of Aboriginal and Torres Strait Islander populations is critical to redress health inequities. This review synthesises evidence of the healthcare experiences amongst Aboriginal and Torres Strait Islander patients through a metanarrative synthesis of qualitative literature.

Methods

A systematic search strategy was developed and applied to six electronic databases between January 2000 and July 2019. Titles and abstracts were screened before applying the inclusion criteria to full text articles. A meta-narrative synthesis was undertaken.

Results

Fifty-four publications were identified from four research traditions; each with a unique conceptualisation of patient experience. Three themes emerged that demonstrate Aboriginal and Torres Strait Islander patient experiences are informed by 1) beliefs about wellbeing and healthcare provision, 2) their level of trust in the healthcare system, and 3) individual and community health system interactions. The findings highlight a range of aspects of patient experience that were important to participating Aboriginal and Torres Strait Islanders in the included studies but not captured currently in health system surveys.

Conclusion

This review highlights the influence of beliefs about health and wellbeing on the patient experience amongst Aboriginal and Torres Strait Islander populations in the Australian health system. Patient experiences were informed by past experience and their trust in the health system. The different factors influencing patient experience and the gravity of their influence must be considered in current approaches to capturing patient experience data collection methods.

Trial registration

PROSPERO (ID: CRD42019134765).
Circular RNA: metabolism, functions and interactions with proteins
Authors: Zhou Wei-Yi , Cai Ze-Rong , Liu Jia , Wang De-Shen , Ju Huai-Qiang , Xu Rui-Hua
Published: December 2020

Circular RNAs (CircRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across species ranging from viruses to mammals. Important advances have been made in the biogenesis, regulation, localization, degradation and modification of circRNAs. CircRNAs exert biological functions by acting as transcriptional regulators, microRNA (miR) sponges and protein templates. Moreover, emerging evidence has revealed that a group of circRNAs can serve as protein decoys, scaffolds and recruiters. However, the existing research on circRNA-protein interactions is quite limited. Hence, in this review, we briefly summarize recent progress in the metabolism and functions of circRNAs and elaborately discuss the patterns of circRNA-protein interactions, including altering interactions between proteins, tethering or sequestering proteins, recruiting proteins to chromatin, forming circRNA-protein-mRNA ternary complexes and translocating or redistributing proteins. Many discoveries have revealed that circRNAs have unique expression signatures and play crucial roles in a variety of diseases, enabling them to potentially act as diagnostic biomarkers and therapeutic targets. This review systematically evaluates the roles and mechanisms of circRNAs, with the hope of advancing translational medicine involving circRNAs.
Correction to: Normofractionated stereotactic radiotherapy versus CyberKnife-based hypofractionation in skull base meningioma: a German and Italian pooled cohort analysis
Authors: Conti Alfredo , Senger Carolin , Acker Güliz , Kluge Anne , Pontoriero Antonio , Cacciola Alberto , Pergolizzi Stefano , Germanò Antonino , Badakhshi Harun , Kufeld Markus , Meinert Franziska , Nguyen Phuong , Loebel Franziska , Vajkoczy Peter , Budach Volker , Kaul David
Published: December 2020

An amendment to this paper has been published and can be accessed via the original article.
Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus
Authors: Grandis M. , Obici L. , Luigetti M. , Briani C. , Benedicenti F. , Bisogni G. , Canepa M. , Cappelli F. , Danesino C. , Fabrizi G. M. , Fenu S. , Ferrandes G. , Gemelli C. , Manganelli F. , Mazzeo A. , Melchiorri L. , Perfetto F. , Pradotto L. G. , Rimessi P. , Tini G. , Tozza S. , Trevisan L. , Pareyson D. , Mandich P.
Published: December 2020

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients’ characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.
Detailed molecular cytogenetic characterisation of the myeloid cell line U937 reveals the fate of homologous chromosomes and shows that centromere capture is a feature of genome instability
Authors: MacKinnon Ruth N. , Peverall Joanne , Campbell Lynda J. , Wall Meaghan
Published: December 2020

Background

The U937 cell line is widely employed as a research tool. It has a complex karyotype. A PICALM-MLLT10 fusion gene formed by the recurrent t(10;11) translocation is present, and the myeloid common deleted region at 20q12 has been lost from its near-triploid karyotype. We carried out a detailed investigation of U937 genome reorganisation including the chromosome 20 rearrangements and other complex rearrangements.

Results

SNP array, G-banding and Multicolour FISH identified chromosome segments resulting from unbalanced and balanced rearrangements. The organisation of the abnormal chromosomes containing these segments was then reconstructed with the strategic use of targeted metaphase FISH. This provided more accurate karyotype information for the evolving karyotype. Rearrangements involving the homologues of a chromosome pair could be differentiated in most instances. Centromere capture was demonstrated in an abnormal chromosome containing parts of chromosomes 16 and 20 which were stabilised by joining to a short section of chromosome containing an 11 centromere. This adds to the growing number of examples of centromere capture, which to date have a high incidence in complex karyotypes where the centromeres of the rearranged chromosomes are identified. There were two normal copies of one chromosome 20 homologue, and complex rearrangement of the other homologue including loss of the 20q12 common deleted region. This confirmed the previously reported loss of heterozygosity of this region in U937, and defined the rearrangements giving rise to this loss.

Conclusions

Centromere capture, stabilising chromosomes pieced together from multiple segments, may be a common feature of complex karyotypes. However, it has only recently been recognised, as this requires deliberate identification of the centromeres of abnormal chromosomes. The approach presented here is invaluable for studying complex reorganised genomes such as those produced by chromothripsis, and provides a more complete picture than can be obtained by microarray, karyotyping or FISH studies alone. One major advantage of SNP arrays for this process is that the two homologues can usually be distinguished when there is more than one rearrangement of a chromosome pair. Tracking the fate of each homologue and of highly repetitive DNA regions such as centromeres helps build a picture of genome evolution. Centromere- and telomere-containing elements are important to deducing chromosome structure. This study confirms and highlights ongoing evolution in cultured cell lines.
The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors
Authors: Jia Xiao-Hui , Geng Lu-Ying , Jiang Pan-Pan , Xu Hong , Nan Ke-Jun , Yao Yu , Jiang Li-Li , Sun Hong , Qin Tian-Jie , Guo Hui
Published: December 2020

The enthusiasm for immune checkpoint inhibitors (ICIs), an efficient tumor treatment model different from traditional treatment, is based on their unprecedented antitumor effect, but the occurrence of immune-related adverse events (irAEs) is an obstacle to the prospect of ICI treatment. IrAEs are a discrete toxicity caused by the nonspecific activation of the immune system and can affect almost all tissues and organs. Currently, research on biomarkers mainly focuses on the gastrointestinal tract, endocrine system, skin and lung. Several potential hypotheses concentrate on the overactivation of the immune system, excessive release of inflammatory cytokines, elevated levels of pre-existing autoantibodies, and presence of common antigens between tumors and normal tissues. This review lists the current biomarkers that might predict irAEs and their possible mechanisms for both nonspecific and organ-specific biomarkers. However, the prediction of irAEs remains a major clinical challenge to screen and identify patients who are susceptible to irAEs and likely to benefit from ICIs.
CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis
Authors: Xu Hanchen , Liu Yujing , Cheng Peiqiu , Wang Chunyan , Liu Yang , Zhou Wenjun , Xu Yangxian , Ji Guang
Published: December 2020

Background

Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer.

Methods

The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms.

Results

CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells.

Conclusions

CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.
High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial
Authors:   the H. F.-AECOPD study investigators, Cortegiani Andrea , Longhini Federico , Madotto Fabiana , Groff Paolo , Scala Raffaele , Crimi Claudia , Carlucci Annalisa , Bruni Andrea , Garofalo Eugenio , Raineri Santi Maurizio , Tonelli Roberto , Comellini Vittoria , Lupia Enrico , Vetrugno Luigi , Clini Enrico , Giarratano Antonino , Nava Stefano , Navalesi Paolo , Gregoretti Cesare
Published: December 2020

Background

The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment.

Methods

We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25–7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes.

Results

Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were − 6.8 mmHg (± 8.7) in the HFNT and − 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis.

Conclusions

HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD.

Trial registration: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).
Newborn screening for congenital hypothyroidism: improvement in short-term follow-up by audit and monitoring
Authors: Majid Hafsa , Ahmed Sibtain , Siddiqui Imran , Humayun Khadija , Karimi Hussain , Khan Aysha Habib
Published: December 2020

Objective

Newborn screening for congenital hypothyroidism (CH) at our hospital during this study was by measurement of thyroid stimulating hormone (TSH) in serum samples. This audit was conducted over a 2 year period, to determine the compliance of reporting of results greater than the screening cutoffs for serum TSH. Gaps of non-compliance were identified, and re-audit was undertaken after the corrective actions were taken.

Results

The critical limit was defined as serum TSH (≥ 20 µIU/ml) following consultation with a pediatric endocrinologist. All results above this limit were reported urgently to physicians. During the audit period, 27,407 tests were performed, 0.7% had a value of ≥ 20 µIU/ml, of those only 62% were reported to the general paediatrician or neonatologist. Reasons for not reporting results included non-availability of contact information, lack of policy awareness by technologists, critical results not highlighted on the computer display, and absence of regular monitoring. Corrective measures were taken, and re-audit was done. During the re-audit period, a total of 22,985 tests was performed, 0.6% had a value of ≥ 20 µIU/ml. Of these, 77% were reported to the general paediatrician or neonatologist. Critical result reporting was improved after the audit, and further enhanced the laboratory service of CH screening.
High-level production of γ-cyclodextrin glycosyltransferase in recombinant Escherichia coli BL21 (DE3): culture medium optimization, enzymatic properties characterization, and product specificity analysis
Authors: Duan Menglu , Wang Yan , Yang Guowu , Li Jiao , Wan Yi , Deng Yuan , Mao Yong
Published: December 2020

Purpose

γ-Cyclodextrin glycosyltransferase (γ-CGTase) catalyzes the biotransformation of low-cost starch into valuable γ-cyclodextrin (γ-CD), which is widely applied in biotechnology, food, and pharmaceutical industries. However, the low specificity and activity of soluble γ-CGTase increase the production cost of γ-CD, thereby limiting its applications. Therefore, the present study aimed at optimizing an economical medium for high production of γ-CGTase by the recombinant Escherichia coli (E. coli) BL21 (DE3) and evaluating its enzymatic properties and product specificity.

Methods

The γ-CGTase production was optimized using the combination of Plackett-Burman experimental design (PBD) and Box-Behnken design-response surface methodology (BBD-RSM). The hydrolysis and cyclization properties of γ-CGTase were detected under the standard assay conditions with buffers of various pHs and different reaction temperatures. The product specificity of γ-CGTase was investigated by high-performance liquid chromatography (HPLC) analysis of three CDs (α-, β-, γ-CD) in the biotransformation product of cassava starch.

Results

The γ-CGTase activity achieved 53992.10 U mL−1 under the optimum conditions with the significant factors (yeast extract 38.51 g L−1, MgSO4 4.19 mmol L−1, NiSO4 0.90 mmol L−1) optimized by the combination of PBD and BBD-RSM. The recombinant γ-CGTase exhibited favorable stability in a wide pH and temperature range and maintained both the hydrolysis and cyclization activity under the pH 9.0 and 50 °C. Further analysis of the products from cassava starch catalyzed by the γ-CGTase reported that the majority (90.44%) of product CDs was the γ form, which was nearly 11% higher than the wild enzyme. Cyclododecanone added to the transformation system could enhance the γ-CD purity to 98.72%, which is the highest purity value during the transformation process reported so far.

Conclusion

The yield of γ-CGTase activity obtained from the optimized medium was 2.83-fold greater than the unoptimized medium, and the recombinant γ-CGTase exhibited a favorable thermal and pH stability, and higher γ-cyclization specificity. These results will provide a fundamental basis for the high productivity and purity of γ-CD in the industrial scale.
ELABELA ameliorates hypoxic/ischemic-induced bone mesenchymal stem cell apoptosis via alleviation of mitochondrial dysfunction and activation of PI3K/AKT and ERK1/2 pathways
Authors: Fu Jiaying , Chen Xuxiang , Liu Xin , Xu Daishi , Yang Huan , Zeng Chaotao , Long Huibao , Zhou Changqing , Wu Haidong , Zheng Guanghui , Wu Hao , Wang Wuming , Wang Tong
Published: December 2020

Background

Mesenchymal stem cells (MSCs) have exerted their brilliant potential to promote heart repair following myocardial infarction. However, low survival rate of MSCs after transplantation due to harsh conditions with hypoxic and ischemic stress limits their therapeutic efficiency in treating cardiac dysfunction. ELABELA (ELA) serves as a peptide hormone which has been proved to facilitate cell growth, survival, and pluripotency in human embryonic stem cells. Although ELA works as an endogenous ligand of a G protein-coupled receptor APJ (Apelin receptor, APLNR), whether APJ is an essential signal for the function of ELA remains elusive. The effect of ELA on apoptosis of MSCs is still vague.

Objective

We studied the role of ELABELA (ELA) treatment on the anti-apoptosis of MSCs in hypoxic/ischemic (H/I) conditions which mimic the impaired myocardial microenvironment and explored the possible mechanisms in vitro.

Methods

MSCs were obtained from donated rats weighing between 80~120 g. MSCs were exposed to serum-free and hypoxic (1% O2) environments for 24 h, which mimics hypoxic/ischemic damage in vivo, using serum-containing normoxic conditions (20% O2) as a negative control. MSCs that were exposed to H/I injury with ELA processing were treated by 5 μM of ELA. Cell viability and apoptosis of MSCs were evaluated by CCK8 and flow cytometry, respectively. Mitochondrial function of MSCs was also assessed according to mitochondrial membrane potential (MMP) and ATP content. The protein expression of key kinases of the PI3K/AKT and ERK1/2 signaling pathways involving t-AKT, p-AKT, t-ERK1/2, and p-ERK1/2, as well as apoptosis-related protein expression of Bcl-2, Bax, and cleaved Caspase 3, were monitored by Western blot.

Results

We found that ELA treatment of H/I-induced MSCs improved overall cell viability, enhanced Bcl/Bax expression, and decreased Caspase 3 activity. ELA inhibited H/I-induced mitochondrial dysfunction by increasing ATP concentration and suppressing the loss of mitochondrial transmembrane potential. However, this anti-apoptotic property of ELA was restrained in APJ-silenced MSCs. Additionally, ELA treatment induced the phosphorylation of AKT and ERK, while the blockade of PI3K/AKT and ERK1/2 pathways with respective inhibitors, LY294002 and U0126, suppressed the action of ELA.

Conclusion

ELA positively affected on the survival of MSCs and exhibited anti-apoptotic characteristics when exposed to hypoxic/ischemic condition in vitro. Also, the function of ELA was correlated with the APJ receptor, reduced mitochondrial damage, and activation of the PI3K/AKT and ERK1/2 signal axes.
Perceived work stress, overcommitment, balance in everyday life, individual factors, self-rated health and work ability among women and men in the public sector in Sweden – a longitudinal study
Authors: Håkansson Carita , Gard Gunvor , Lindegård Agneta
Published: December 2020

Background

The aim was to investigate whether perceived work stress, overcommiment, balance in everyday life, individual factors and self-rated health in combination predict work ability among women and men in the public sector in Sweden.

Methods

A sample was randomly selected from the employee records of the participating public health care organisation in Western Sweden. In total, 2223 employees were included and answered a postal survey twice, at a 2 year interval. The survey included questions about work ability, perceived work stress, overcommitment, balance in everyday life, individual factors and self-rated health. Odds ratios with 95% confidence intervals for work ability were estimated using logistic regression.

Results

Imbalance in everyday life and overcommitment predicted reduced work ability in women and imbalance in everyday life and low educational level predicted reduced work ability in men. However, when poor self-rated health was added to the models this was the strongest predictor of work ability for both genders.

Conclusion

A combination of poor self-rated health, imbalance in everyday life, and overcommitment predicted reduced work ability. This multifactorial nature of work ability should be taken into account in health promotion programmes.
Radiologic results of additional single screw fixation with lateral locking plate after hybrid closed-wedge high tibial osteotomy
Authors: Hiraoka Nobuyuki , Nakagawa Shuji , Otakara Eigo , Inoue Hiroaki , Takahashi Kenji , Arai Yuji
Published: December 2020

Background

Hybrid closed-wedge high tibial osteotomy (hybrid CWHTO) is an effective surgical treatment for medial compartment osteoarthritis of the knee. Our study investigated whether the combination of a lateral locking plate and a single medial screw promoted bone union after hybrid CWHTO.

Methods

The study cohort consisted of 30 patients (15 men and 15 women) who underwent hybrid CWHTO for medial compartment osteoarthritis or spontaneous osteonecrosis of the knee. Sixteen knees were fixed with a lateral locking plate (LP group), and 17 were fixed with both a lateral locking plate and a cannulated cancellous screw on the medial side of the tibia (LPS group). The times to bone union, radiolucency, and callus formation at the osteotomy site were evaluated radiographically.

Results

The mean postoperative time to radiographic confirmation of bone union was 5.5 ± 2.6 months in the LP group and 3.4 ± 1.5 months in the LPS group. Radiolucency at the osteotomy site and excess callus formation on the posterior side of the tibia were lower in the LPS group than in the LP group.

Conclusions

This modified hybrid CWHTO combining a lateral locking plate and a cannulated cancellous screw on the medial side of the tibia improves the stability of the osteotomy site and shortens the period of bone union.
Case Report: A castration-resistant terminal prostate cancer patient’s survival prolonged after practicing Falun Gong
Authors: Dong Yu-Hong , Wu Shawn , Corson Ann , Hsu Kai-Hsiung
Published: December 2020

Background: Most metastatic prostate cancer patients receive combined androgen blockade (CAB) as the mainstay of treatment. Unfortunately, patients ultimately progress to castration resistance.

Clinical finding and diagnosis: We describe a man in his eighties who developed stage IV, M1b prostate cancer, multiple (≥5) bone metastases, and required the aid of a walker to ambulate. Without treatment, his treating physician predicted he would survive 6 months.

Interventions and outcomes: The patient initially responded well to treatment with CAB, but during the 68-80th week of treatment he developed castration resistance. Bicalutamide was then discontinued. He chose to begin practicing Falun Gong (FLG) at week 89 as an alternative form of care while continuing two doses of leuprolide acetate. His PSA decreased by 86% within five weeks, he walked independently at 17 weeks and bone metastases disappeared in 41-43 weeks after beginning to practice Falun Gong. He also reported better psychosocial functioning. His treating physician assessed that his prostate malignancy was “clinically, under control” and “his overall functional status is excellent.” The patient survived a total of 263 weeks (61.4 months) post-diagnosis, including 183 weeks (42.3 months) after developing castration resistance.

Conclusion: This castration-resistant terminal prostate cancer patient gained significant clinical benefits after practicing Falun Gong.