bluuebunny/crossref_metadata_2025 huggingface dataset:
A cohort study and meta-analysis of the evidence for consideration of Lauren subtype when prescribing adjuvant or palliative chemotherapy for gastric cancer
Authors: Wang Kunning , Li Enxiao , Busuttil Rita A. , Kong Joseph C. , Pattison Sharon , Sung Joseph J. Y. , Yu Jun , El-Omar Emad M. , Simpson Julie A. , Boussioutas Alex
Published: July 2020

Background:

The association between the survival or efficacy of chemotherapy and the Lauren subtype of gastric cancer (GC) remains unclear. We aimed to clarify whether patients with different Lauren subtypes have different survival after treatment with systemic chemotherapy: intestinal gastric cancer (IGC) patients survived better than patients with mixed type gastric cancer (MGC) or diffuse gastric cancer (DGC) after treatment with systemic chemotherapy.

Patients & methods:

Relevant studies for the meta-analysis were identified through searching Pubmed, Embase, Cochrane and Ovid up to March 2020. We also included our own prospectively collected cohort of patients that were followed over a 10-year period. Sub-group and sensitivity analyses were also performed.

Results:

In our prospective cohort, the overall survival (OS) of IGC patients receiving systemic chemotherapy (chemoIGC) [median OS 5.01 years, interquartile range (IQR) 2.63–6.71] was significantly higher than that of DGC patients receiving the same chemotherapy (chemoDGC) (median OS 1.33 years, IQR 0.78–3.33, p = 0.0001). After adjusting for age, gender and cancer stage, there was a significant difference in OS in patients treated with chemotherapy based on the Lauren classification of GC {hazard ratio (HR) for OS of the IGC versus DGC 0.33, [95% confidence interval (CI), 0.17–0.65; p < 0.001]}. In the IGC patients, the adjusted HR associated with chemotherapy was 0.26 (95% CI, 0.12–0.56; p = 0.001), whereas the association was 0.64 (95% CI, 0.30–1.33; p = 0.23) in the DGC patient group. In our meta-analysis, 33 studies comprising 10,246 patients treated with systemic chemotherapy (chemoIGC n = 4888, chemoDGC n = 5358) met all the selection criteria. While we accounted for much of the heterogeneity in these studies, we found that chemoIGC patients showed significantly improved OS [HR, 0.76 (95% CI, 0.71–0.82); p < 0.00001] when compared with similarly treated chemoDGC patients.

Conclusion:

Our results support the consideration of Lauren subtype when prescribing systemic chemotherapy for GC, particularly for MGC or DGC, which may not benefit from chemotherapy. Lauren classification should be considered to stratify chemotherapy regimens to GC patients in future clinical trials, with particular relevance to MGC or DGC, which is more difficult to treat with current regimens.
Synergistic antitumor effect of 5-fluorouracil with the novel LSD1 inhibitor ZY0511 in colorectal cancer
Authors: Peng Wen , Zhang Huaqing , Tan Shisheng , Li Yan , Zhou Yang , Wang Liang , Liu Chunqi , Li Qiu , Cen Xiaobo , Yang Shengyong , Zhao Yinglan
Published: July 2020

Background:

Lysine-specific histone demethylase 1 (LSD1) is a potential target of cancer therapy. In the present study, we aimed to investigate the combined antitumor activity of a novel LSD1 inhibitor (ZY0511) with 5-fluorouracil (5-FU) and elucidate the underlying mechanism in colorectal cancer (CRC).

Methods:

We evaluated LSD1 expression in CRC tissues from patients who received 5-FU treatment. The synergistic antitumor effect of 5-FU with ZY0511 against human CRC cells was detected both in vitro and in vivo. The underlying mechanism was explored based on mRNA sequencing (mRNA-seq) technology.

Results:

Overexpression of LSD1 was observed in human CRC tissues, and correlated with CRC development and 5-FU resistance. ZY0511, a novel LSD1 inhibitor, effectively inhibited CRC cells proliferation, both in vitro and in vivo. Notably, the combination of ZY0511 and 5-FU synergistically reduced CRC cells viability and migration in vitro. It also suppressed Wnt/β-catenin signaling and DNA synthesis pathways, which finally induced apoptosis of CRC cells. In addition, the combination of ZY0511 with 5-FU significantly reduced CRC xenograft tumor growth, along with lung and liver metastases in vivo.

Conclusions:

Our findings identify LSD1 as a potential marker for 5-FU resistance in CRC. ZY0511 is a promising candidate for CRC therapy as it potentiates 5-FU anticancer effects, thereby providing a new combinatorial strategy for treating CRC.
Labors of Reading in Post Qualitative Inquiry
Authors: Kuecker Elliott
Published: July 2020

This paper considers the role reading plays in post qualitative inquiry, arguing that because post qualitative inquiry is a derivative of poststructuralism, the philosophies of reading that are foundational to poststructuralism are then axiomatic to post qualitative inquiry. This is evidenced by Elizabeth St. Pierre’s relentless reminders to become students of poststructuralism before using post qualitative inquiry in one’s scholarship. Drawing on Roland Barthes’s philosophy of reading, this paper deconstructs post qualitative inquiry’s deep relationship to reading in order to critique the way this genre at times risks falling for glamour of high theory and foundational misconceptions about poststructuralism’s interrogation of subjectivity.
Digital Eco System: Cyber Bodies, Cyber Lives, and Cyber Narratives
Authors: Atay Ahmet
Published: July 2020

In this essay, I try to embody the fragmented nature of our digital culture and lives. Through autoethnographic writing and personal vignettes, I narrate and theorize five interrelated themes: interactivity, the co-construction of digital stories, blurring the idea of time and space, the concept of transnational cyber bodies, and finally, the notion of a transnational and queer cyber home. Hence, my goal is to present personal stories that embody forms of cyber or digital autoethnography.
Enhancing Your Virtual Footprint: The School Nurse’s Professional Health Office Website
Authors: Moss Eileen
Published: July 2020

The public narrative of the role of the school nurse is about Band-Aids and management of acute illness and injury. The public does not understand that school nurses are responsible for so much more. Literature recommends that school nurses change the narrative of school nursing by the use of social media and websites, but school nurses are not using websites as evidenced by a national audit of websites and survey of school nurses. The school nurse website toolkit was developed to assist nurses in the development of their own professional practice websites, thereby enhancing their image to stakeholders and changing the public narrative of school nursing.
Barriers and Facilitators of Family Planning Use in Fishing Communities of Lake Victoria in Uganda
Authors: Nanvubya Annet , Wanyenze Rhoda Kitty , Kamacooko Onesmus , Nakaweesa Teddy , Mpendo Juliet , Kawoozo Barbarah , Matovu Francis , Nabukalu Sarah , Omoding Geoffrey , Kaweesi Jed , Ndugga John , Bagaya Bernard , Chinyenze Kundai , Price Matt , Van Geertruyden Jean Pierre
Published: July 2020

Introduction: Family planning (FP) is a key element in the conduct of research and is essential in managing family sizes. Although fishing communities (FCs) are targeted populations for HIV prevention research, their FP practices are poorly understood. We explored barriers and facilitators of FP use in FCs of Lake Victoria in Uganda. Methods: We employed a mixed-methods approach comprising a cross-sectional survey, in-depth interviews, and focus group discussions in 2 FCs. Multivariable logistic regression was used to analyze quantitative data and a thematic approach to generate themes from the qualitative data. Results: Up to 1410 individuals participated in the survey and 47 in the qualitative study. Just over a third (35.6%) used FP. The most commonly used methods were condoms, pills, and injectables. In Kigungu community, participants whose religion was Anglican and Muslim were more likely to use FP than Catholics (adjusted odds ratio [aOR] 1.45; 95% CI 1.05-1.99 and aOR 1.45; 95% CI 1.05-2.07, respectively). Participants were more likely to use FP if they had satisfactory FP knowledge compared to those with no satisfactory FP knowledge (aOR 1.79; 95% CI 1.23-2.61), or if they were married compared to their single counterparts (aOR 1.84; 95% CI 1.32-2.57). In both communities, participants were more likely to use FP if they had 2 or more sexual partners in the past 12 months than those with less than 2 sexual partners (aOR 1.41 95% CI 1.07-1.87 and aOR 2.60; 95% CI 1.36-4.97). Excessive bleeding and delayed fecundity; fertility desire; gender preferences of children; method stock outs and lack of FP trained personnel constituted barriers to FP use. There were also cultural influences in favor of large families. Conclusion: FP use in FCs is suboptimal. Barriers of FP use were mainly biomedical, religious, social, and cultural, which underscores a need for FP education and strengthening of FP service provision in FCs.
Destabilization of an urban subsystem by a virtual collapse in its space–time structure
Authors: Smith Terence R
Published: July 2020

It is shown that a virtual collapse in the space–time structure of a geographically distributed system may induce changes in the information flow field of the system and lead to instability. A case study of the commercial banking system of New York City demonstrates how a virtual collapse in the space–time structure of its check clearing process led to a transformed information flow environment in which banks had, for the first time, accurate and timely information concerning the decision-making processes of other banks. A dynamical systems model representing the behavior of the banks, both before and after the transformation, demonstrates how their competitive use of this information led to decision-making based on the decisions of others. This process of internal referencing resulted in a structurally unstable state in which perturbations, arising from asymmetric responses to seasonally changing deposit flows, accumulated with little or no decay. This caused loans to diverge from deposits and made the system susceptible to random financial perturbations that led to a banking panic. While the behavior of the aggregate system was structurally unstable, the behavior of the individual banks was stable, with the banks behaving as a coherent group. The internal referencing structural instability is of general significance for the aggregate behavior of geographically distributed systems that undergo a virtual collapse in their space–time structures and a transformation of their information flow fields.
The dirty work of the Stanford Prison Experiment: Re-reading the dramaturgy of coercion
Authors: Scott-Bottoms Stephen
Published: July 2020

Almost 50 years on, the Stanford Prison Experiment of 1971 remains one of the most notorious and controversial psychology studies ever devised. It has often been treated as a cautionary tale about what can happen in prison situations if there is inadequate staff training or safeguarding, given the inherent power differentials between staff and inmates. But what exactly was the ‘situation’ in the simulated prison at Stanford University, and how exactly did the participants respond to it? This article provides a new analysis of the behaviour of the nine Stanford ‘guards’, which draws on unpublished archival records and original interviews with some of the participants. It adopts an interactionist approach, whereby the individual backgrounds and personalities of the participants are seen to inform their behaviour within the situation provided, as well as vice versa. A key suggestion to emerge from this analysis is that the conduct of the three guard shifts, within the experiment, differed significantly according the interaction of the men on each shift and their influence on each other. The article is framed by the concept of ‘dirty work’ and uses theoretical sources including Goffman and Festinger to explore the extent to which the adoption of a particular social role (in this case, that of prison guard) affects change in the behaviour and beliefs of individual role players. The argument seeks to show that some of the Stanford guards adopted strategies of ‘role distancing’ to insulate themselves from the coercive demands of their positions, while others found the guard role impacting troublingly on their senses of self.
Overexpression of the Transcription Factor Gene OsSTAP1 Increases Salt Tolerance in Rice
Authors: Wang Yinxiao , Wang Juan , Zhao Xiuqin , Yang Sheng , Huang Liyu , Du Fengping , Li Zhikang , Zhao Xiangqiang , Fu Binying , Wang Wensheng
Published: July 2020

Background

High soil salinity can cause significant losses in rice productivity worldwide, mainly because salt inhibits plant growth and reduces grain yield. To cope with environmental changes, plants have evolved several adaptive mechanisms that involve the regulation of many stress-responsive genes.

Results

In this study, we identified OsSTAP1, which encodes an AP2/ERF-type transcription factor, was rapidly induced by ABA, ACC, salt, cold, and PEG treatments. OsSTAP1 is localized to the nucleus and acts as a transcriptional activator in plant cells. Compared with wild type, transgenic lines overexpressing OsSTAP1 exhibited increased tolerance to salt stress with higher SOD, POD, and CAT activities, and lower Na+/K+ ratios in the shoots. In addition, many other stress-responsive genes, including other ERF- and peroxidase-encoding genes, were upregulated in the OsSTAP1-overexpression lines.

Conclusion

This study suggests that OsSTAP1 functions as an AP2/ERF transcriptional activator, and plays a positive role in salt tolerance by decreasing the Na+/K+ ratio and maintaining cellular redox homeostasis.
Haemorrhagic cystitis due to cytomegalovirus in a patient with AIDS
Authors: Padayachee Winston P. R. , Sadhwani Sanjay , Doherty Sean W. , Mukendi Alain Mwamba , Van den Berg Eunice , Botha Adam R.
Published: July 2020

Background

Cytomegalovirus-related infections are commonly seen in immunocompromised patients. However, haemorrhagic cystitis is an exceptionally rare associated manifestation. We present an unusual case of cytomegalovirus-related haemorrhagic cystitis in a patient with acquired immune deficiency syndrome (AIDS).

Case presentation

A 33-year-old HIV-positive female presented with acute gross haematuria and suprapubic pain. Cystoscopy revealed features suggestive of haemorrhagic cystitis with clots in the bladder and an ulcerative lesion on the left lateral wall which was biopsied. Histology demonstrated the presence of enlarged cells containing eosinophilic intranuclear and ill-defined amphophilic intracytoplasmic inclusions. Immunohistochemistry was positive for cytomegalovirus.

Conclusion

This case appears to be the first of its kind reported in South Africa highlighting the importance of considering cytomegalovirus as a potential infectious aetiology in AIDS patients with haematuria. Bladder irrigation with normal saline with or without clot evacuation combined with Ganciclovir are associated with good outcome.
Potential Drugs and Remedies for the Treatment of COVID-19: a Critical Review
Authors: Barati Fatemeh , Pouresmaieli Mahdi , Ekrami Elena , Asghari Sahar , Ziarani Farzad Ramezani , Mamoudifard Matin
Published: July 2020

COVID-19 disease with a high rate of contagious and highly nonspecific symptoms, is an infectious disease caused by a newly discovered coronavirus. Most people who fall sick with COVID-19 will experience mild to moderate symptoms such as respiratory symptoms, cough, dyspnea, fever, and viral pneumonia and recover without any special cure. However, some others need special and emergency treatment to get rid of this widespread disease. Till now, there are numbers of proposed novel compounds as well as standards therapeutics agent existed for other conditions seems to have efficacy against the 2019-nCoV. Some which are being tested for MERS-CoV and SARS-CoV are validated that could be also efficient against this new coronavirus. However, there are currently no effective specific antivirals or drug combinations introduced for 2019-nCoV specifically that be supported by high-level evidence. The main purpose of this paper is to review typical and ongoing treatments for coronavirus disease including home remedies, herbal medicine, chemical drugs, plasma therapy, and also vaccinies. In this regards, famous herbal medicines and common chemical drugs which are routinely to be prescribed for patients are introduced. Moreover, a section is assigned to the drug interactions and some outdated drugs which have been proved to be inefficient. We hope that this work could pave the way for researchers to develop faster and more reliable methods for earlier treatment of patients and rescue more people.

Graphical abstract
imputeqc: an R package for assessing imputation quality of genotypes and optimizing imputation parameters
Authors: Khvorykh Gennady V. , Khrunin Andrey V.
Published: July 2020

Background

The imputation of genotypes increases the power of genome-wide association studies. However, the imputation quality should be assessed in each particular case. Nevertheless, not all imputation softwares control the error of output, e.g., the last release of fastPHASE program (1.4.8) lacks such an option. In this particular software there is also an uncertainty in choosing the model parameters. fastPHASE is based on haplotype clusters, which size should be set a priori. The parameter influences the results of imputation and downstream analysis.

Results

We present a software toolkit imputeqc to assess the imputation quality and/or to choose the model parameters for imputation. We demonstrate the efficacy of toolkit for evaluation of imputations made with both fastPHASE and BEAGLE software for HapMap and 1000 Genomes data. The discordance of genotypes received correlated well in both methods. Using imputeqc, we also shown how to choose the optimal number of haplotype clusters and expectation-maximization cycles for fastPHASE program. The found number of haplotype clusters of 25 was further applied for hapFLK testing that revealed signatures of selection at LCT region on chromosome 2. We also demonstrated how to decrease the computational time in the case of hapFLK testing from 3 days to 20 h.

Conclusions

The toolkit is implemented as an R package imputeqc and command line scripts. The code is freely available at https://github.com/inzilico/imputeqcunder the MIT license.
Type 2 diabetes susceptibility genes on mouse chromosome 11 under high sucrose environment
Authors: Kobayashi Misato , Ueda Hironori , Babaya Naru , Itoi-Babaya Michiko , Noso Shinsuke , Fujisawa Tomomi , Horio Fumihiko , Ikegami Hiroshi
Published: July 2020

Background

Both genetic and environmental factors contribute to type 2 diabetes development. We used consomic mice established from an animal type 2 diabetes model to identify susceptibility genes that contribute to type 2 diabetes development under specific environments. We previously established consomic strains (C3H-Chr 11NSY and C3H-Chr 14NSY) that possess diabetogenic Chr 11 or 14 of the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of spontaneous type 2 diabetes, in the genetic background of C3H mice. To search genes contribute to type 2 diabetes under specific environment, we first investigated whether sucrose administration deteriorates type 2 diabetes-related traits in the consomic strains. We dissected loci on Chr 11 by establishing congenic strains possessing different segments of NSY-derived Chr 11 under sucrose administration.

Results

In C3H-Chr 11NSY mice, sucrose administration for 10 weeks deteriorated hyperglycemia, insulin resistance, and impaired insulin secretion, which is comparable to NSY mice with sucrose. In C3H-Chr 14NSY mice, sucrose administration induced glucose intolerance, but not insulin resistance and impaired insulin secretion. To dissect the gene(s) existing on Chr 11 for sucrose-induced type 2 diabetes, we constructed four novel congenic strains (R1, R2, R3, and R4) with different segments of NSY-derived Chr 11 in C3H mice. R2 mice showed marked glucose intolerance and impaired insulin secretion comparable to C3H-Chr 11NSY mice. R3 and R4 mice also showed impaired insulin secretion. R4 mice showed significant decreases in white adipose tissue, which is in the opposite direction from parental C3H-Chr 11NSY and NSY mice. None of the four congenic strains showed insulin resistance.

Conclusions

Genes on mouse Chr 11 could explain glucose intolerance, impaired insulin secretion, insulin resistance in NSY mice under sucrose administration. Congenic mapping with high sucrose environment localized susceptibility genes for type 2 diabetes associated with impaired insulin secretion in the middle segment (26.0–63.4 Mb) of Chr 11. Gene(s) that decrease white adipose tissue were mapped to the distal segment of Chr 11. The identification of diabetogenic gene on Chr 11 in the future study will facilitate precision medicine in type 2 diabetes by controlling specific environments in targeted subjects with susceptible genotypes.
Geographic mapping of Enterobacteriaceae with extended-spectrum β-lactamase (ESBL) phenotype in Pereira, Colombia
Authors: Arias Ramos Deving , Hoyos Pulgarín Julián Andrés , Moreno Gómez Germán Alberto , Alzate John Alexander , Olaya Gómez Juan Camilo , Cortés Bonilla Isabella , Vargas Mosquera Camila
Published: July 2020

Background

Antimicrobial resistance is an ecological and multicausal problem. Infections caused by extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E) can be acquired and transmitted in the community. Data on community-associated ESBL-E infections/colonizations in Colombia are scarce. Georeferencing tools can be used to study the dynamics of antimicrobial resistance at the community level.

Methods

We conducted a study of geographic mapping using modern tools based on geographic information systems (GIS). Two study centers from the city of Pereira, Colombia were involved. The records of patients who had ESBL-producing Enterobacteriaceae were reviewed. Antimicrobial susceptibility testing and phenotypic detection of ESBL was done according to CLSI standards.

Results

A population of 415 patients with community-acquired infections/colonizations and 77 hospital discharges were obtained. Geographic distribution was established and heat maps were created. Several hotspots were evidenced in some geographical areas of the south-west and north-east of the city. Many of the affected areas were near tertiary hospitals, rivers, and poultry industry areas.

Conclusions

There are foci of antimicrobial resistance at the community level. This was demonstrated in the case of antimicrobial resistance caused by ESBL in a city in Colombia. Causality with tertiary hospitals in the city, some rivers and the poultry industry is proposed as an explanation of the evidenced phenomenon. Geographic mapping tools are useful for monitoring antimicrobial resistance in the community.
Comparison of the therapeutic effects of surgery following prism adaptation test versus surgery alone in acute acquired comitant esotropia
Authors: Zhang Peng , Zhang Ying , Gao Lei , Yang Jun
Published: July 2020

Background

To compare the therapeutic effects of surgery following prism adaptation test versus surgery alone in acute acquired comitant esotropia (AACE).

Methods

A total of 46 patients with AACE were enrolled in this retrospective study. Among them, 26 patients underwent surgery following prism adaptation test (combination group) and 20 patients underwent surgery alone (surgery group). The following parameters were evaluated including success rate, distant and near deviation angles, visual function, and near stereoacuity.

Results

There were no significant differences in success rate between the combination group and surgery group at post-treatment 12 months (96.15% vs. 90.00%,p > 0.05). The postoperative distant and near deviation angles in two groups were significantly lower than that before surgery (p < 0.05). In addition, the numbers of patients with stereopsis postoperatively in two groups were significantly higher than that before surgery (allp < 0.05). Moreover, the numbers of patients with stereopsis and central stereopsis in the combination group were significantly higher than that in the surgery group postoperatively. At post-treatment 12 months, one (3.85%) case recurred in combination group and three (15.00%) cases in the surgery group. No complications were observed in the two groups.

Conclusions

Both approaches had therapeutic benefit in AACE. Surgery following prism adaptation test had better treatment benefits than surgery alone in improving binocular function and reducing recurrence rate.
Utilization of public health care by people with private health insurance: a systematic review and meta-analysis
Authors: Zhang Congcong , Fu Chenwei , Song Yimin , Feng Rong , Wu Xinjuan , Li Yongning
Published: July 2020

Background

The objective of this systematic review was to explore the association between private health insurance and health care utilization.

Methods

We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases for relevant articles since 2010. Studies were eligible if they described original empirical research on the utilization of public health care by individuals with private health insurance, compared with individuals without private insurance. A pooled measure of association between insurance status with health care utilization was assessed through meta-analysis.

Results

Twenty-six articles were included in the final analysis. We found that patients with private insurance did not use more public health care than people without private insurance (P < 0.05). According to the subgroup analysis, people with private insurance were more likely to be hospitalized than people with no insurance (OR 1.67; 95% CI, 1.18 to 2.36).

Conclusions

People with private insurance did not increase their use of health care (outpatient services), compared to those without private insurance. Private health insurance coverage may ease the financial burden on patients and on the public health insurance system.
A systems approach for optimizing implementation to impact: meeting report and proceedings of the 2019 In the Trenches: Implementation to Impact International Summit
Authors: Hanney Stephen R. , Ovseiko Pavel V. , Graham Kathryn E. R. , Chorzempa Heidi , Miciak Maxi
Published: July 2020

Background

The In the Trenches series of cutting-edge knowledge sharing events on impact for front-line experts and practitioners provides an engagement platform for diverse stakeholders across government, research funding organizations, industry, and academia to share emerging knowledge and practical experiences. The second event of the series In the Trenches: Implementation to Impact International Summit was held in Banff, Alberta, Canada, on June 7–8, 2019. The overarching vision for the Summit was to create an engagement platform for addressing key challenges and finding practical solutions to move from implementation (i.e. putting findings into effect) to impact (i.e. creating benefits to society and the economy).

Processes and proceedings

The Summit used diverse approaches to facilitate active engagement and knowledge sharing between 80 delegates across sectors and jurisdictions. Summit sessions mostly consisted of short talks and moderated panels grouped into eight thematic sessions. Each presentation included a summary of Key Messages, along with a summary of the Actionable Insights which concluded each session. The presentations and discussions are analysed, synthesized and described in this proceedings paper using a systems approach. This demonstrates how the Summit focused on each of the necessary functions (and associated components) that should be undertaken, and combined, for effective research and innovation: stewardship and governance, securing finance, creating capacity, and producing and using research. The approach also identifies relevant challenges.

Conclusions

There is increased interest globally in the benefits that can accrue from adopting a systems approach to research and innovation. Various organizations in Canada and internationally have made considerable progress on Implementation to Impact, often as a result of well-planned initiatives. The Summit highlights the value of 1) collaboration between researchers and potential users, and 2) the adoption by funders of approaches involving an increasing range of responsibilities and activities. The Summit website (https://inthetrenchessummit.com/) will be periodically updated with new resources and information about future In the Trenches events.
The need for a holistic approach for SSc-ILD – achievements and ambiguity in a devastating disease
Authors: Hoffmann-Vold Anna-Maria , Allanore Yannick , Bendstrup Elisabeth , Bruni Cosimo , Distler Oliver , Maher Toby M. , Wijsenbeek Marlies , Kreuter Michael
Published: July 2020

Systemic sclerosis (SSc) is a multi-organ autoimmune disease with complex interactions between immune-mediated inflammatory processes and vascular pathology leading to small vessel obliteration, promoting uncontrolled fibrosis of skin and internal organs. Interstitial lung disease (ILD) is a common but highly variable manifestation of SSc and is associated with high morbidity and mortality. Treatment approaches have focused on immunosuppressive therapies, which have shown some efficacy on lung function. Recently, a large phase 3 trial showed that treatment with nintedanib was associated with a reduction in lung function decline. None of the conducted randomized clinical trials have so far shown convincing efficacy on other outcome measures including quality of life determined by patient reported outcomes. Little evidence is available for non-pharmacological treatment and supportive care specifically for SSc-ILD patients, including pulmonary rehabilitation, supplemental oxygen, symptom relief and adequate information. Improved management of SSc-ILD patients based on a holistic approach is necessary to support patients in maintaining as much quality of life as possible throughout the disease course and to improve long-term outcomes.
A novel knock out strategy to enhance recombinant protein expression in Escherichia coli
Authors: Sharma Ashish K. , Shukla Esha , Janoti Deepak S. , Mukherjee Krishna J. , Shiloach Joseph
Published: July 2020

Background

The expression of recombinant proteins triggers a stress response which downregulates key metabolic pathway genes leading to a decline in cellular health and feedback inhibition of both growth and protein expression. Instead of individually upregulating these downregulated genes or improving transcription rates by better vector design, an innovative strategy would be to block this stress response thereby ensuring a sustained level of protein expression.

Results

We postulated that the genes which are commonly up-regulated post induction may play the role of signalling messengers in mounting the cellular stress response. We identified those genes which have no known downstream regulatees and created knock outs which were then tested for GFP expression. Many of these knock outs showed significantly higher expression levels which was also sustained for longer periods. The highest product yield (Yp/x) was observed in a BW25113ΔcysJ knock out (Yp/x 0.57) and BW25113ΔelaA (Yp/x 0.49), whereas the Yp/x of the control W3110 strain was 0.08 and BW25113 was 0.16. Double knock out combinations were then created from the ten best performing single knock outs leading to a further enhancement in expression levels. Out of 45 double knock outs created, BW25113ΔelaAΔyhbC (Yp/x 0.7) and BW25113ΔcysJΔyhbC (Yp/x 0.64) showed the highest increase in product yield compared to the single gene mutant strains. We confirmed the improved performance of these knock outs by testing and obtaining higher levels of recombinant asparaginase expression, a system better suited for analysing sustained expression since it gets exported to the extracellular medium.

Conclusion

Creating key knock outs to block the CSR and enhance expression is a radically different strategy that can be synergistically combined with traditional methods of improving protein yields thus helping in the design of superior host platforms for protein expression.
Long-term transmission patterns and public health policies leading to malaria elimination in Panamá
Authors: Hurtado Lisbeth , Cumbrera Alberto , Rigg Chystrie , Perea Milixa , Santamaría Ana María , Chaves Luis Fernando , Moreno Dianik , Romero Luis , Lasso Jose , Caceres Lorenzo , Saldaña Azael , Calzada Jose E.
Published: July 2020

Background

The present study provides a countrywide perspective of the malaria situation in Panamá over a long-term framework, with the purpose of identifying historical malaria resurgence events and their potential causes.

Methods

A descriptive-ecological study was conducted by analysing demographic and epidemiological annual malaria time series data in Panamá (1884–2019) using several data sources. Malaria intensity indicators were calculated during the study period. The effects of El Niño Southern Oscillation on malaria transmission were also analysed using a retrospective analysis of malaria cases between 1957 and 2019.

Results

Several factors were identified responsible for malaria resurgence in Panamá, mostly related with Malaria Control Programme weakening. During the past 20 years (2000–2019) malaria has progressively increased in prevalence within indigenous settlements, with a predominance of male cases and a high proportion (15% of total cases) in children less than 5 years old. During this period, a significant and increasing proportion of thePlasmodium falciparumcases were imported. Retrospective analysis (1957–2019) evidenced that ENSO had a significant impact on malaria transmission dynamics in Panamá.

Conclusions

Data analysis confirmed that although authorities have been successful in focalizing malaria transmission in the country, there are still neglected issues to be solved and important intercultural barriers that need to be addressed in order to achieve elimination of the disease by 2022. This information will be useful for targeting strategies by the National Malaria Elimination Programme.
Lipoprotein (a) as a residual risk factor for atherosclerotic renal artery stenosis in hypertensive patients: a hospital-based cross-sectional study
Authors: Hu Xiangming , Yang Xing , Li Xida , Luo Demou , Zhou Yingling , Dong Haojian
Published: July 2020

Background

Low-density lipoprotein cholesterol (LDL-c) has been proven to be a risk factor for atherosclerotic cardiovascular disease (CVD), while lipoprotein (a) (Lp(a)) is a residual risk factor for CVD, even though LDL-c is well controlled by statin use. Importantly, the role of Lp(a) in atherosclerotic renal artery stenosis (ARAS) is still unknown.

Methods

For this hospital-based cross-sectional study, patients who simultaneously underwent coronary and renal angiography were examined. ARAS was defined as a 50% reduction in the cross-sectional (two-dimensional plane) area of the renal artery. Data were collected and compared between ARAS and non-ARAS groups, including clinical history and metabolite profiles. Univariate analysis, three tertile LDL-c-based stratified analysis, and multivariate-adjusted logistic analysis were conducted, revealing a correlation between Lp(a) and ARAS.

Results

A total of 170 hypertensive patients were included in this study, 85 with ARAS and 85 with non-RAS. Baseline information indicated comparability between the two groups. In the univariate and multivariate analysis, common risk factors for atherosclerosis were not significantly different. Stratified analysis of LDL-c revealed a significant increase in the incidence of ARAS in patients who had high Lp(a) concentrations at low LDL-c levels (odds ratio (OR): 4.77, 95% confidence interval (CI): 1.04–21.79, P = 0.044). Further logistic analysis with adjusted covariates also confirmed the result, indicating that high Lp(a) levels were independently associated with ARAS (adjusted OR (aOR): 6.14, 95%CI: 1.03–36.47, P = 0.046). This relationship increased with increasing Lp(a) concentration based on a curve fitting graph. These results were not present in the low and intermediate LDL-c-level groups.

Conclusion

In hypertensive patients who present low LDL-c, high Lp(a) was significantly associated with atherosclerotic renal artery stenosis and thus is a residual risk factor.
A cohort study evaluating the association between concurrent mental disorders, mortality, morbidity, and continuous treatment retention for patients in opioid agonist treatment (OAT) across Ontario, Canada, using administrative health data
Authors: Morin Kristen A. , Eibl Joseph K. , Gauthier Graham , Rush Brian , Mushquash Christopher , Lightfoot Nancy E. , Marsh David C.
Published: July 2020

Background

Due to the high prevalence of mental disorders among people with opioid use disorder, the objective of this study was to determine the association between concurrent mental disorders, mortality, morbidity, and continuous treatment retention for patients in opioid agonist treatment in Ontario, Canada.

Methods

We conducted a retrospective cohort study of patients enrolled in opioid agonist treatment between January 1, 2011, and December 31, 2015. Patients were stratified into two groups: those diagnosed with concurrent mental disorders and opioid use disorder and those with opioid use disorder only, using data from the Ontario Health Insurance Plan Database, Ontario Drug Benefit Plan Database. The primary outcome studied was all-cause mortality using data from the Registered Persons Database. Emergency department visits from the National Ambulatory Care Database, hospitalizations Discharge Abstract Database, and continuous retention in treatment, defined as 1 year of uninterrupted opioid agonist treatment using data from the Ontario Drug Benefit Plan Database were measured as secondary outcomes. Encrypted patient identifiers were used to link information across databases.

Results

We identified 55,924 individuals enrolled in opioid agonist treatment, and 87% had a concurrent mental disorder diagnosis during this period. We observed that having a mental disorder was associated with an increased likelihood of all-cause mortality (odds ratio (OR) 1.4; 95% confidence interval (CI) 1.2–1.5). For patients diagnosed with mental disorders, the estimated rate of ED visits per year was 2.25 times higher and estimated rate of hospitalization per year was 1.67 times higher than for patients with no mental disorders. However, there was no association between having a diagnosis of a mental disorder and 1-year treatment retention in OAT-adjusted hazard ratio (HR) = 1.0; 95% CI 0.9 to 1.1.

Conclusion

Our findings highlight the consequences of the high prevalence of mental disorders for individuals with opioid use disorder in Ontario, Canada.
German version of the Chedoke McMaster arm and hand activity inventory (CAHAI-G): intra-rater reliability and responsiveness
Authors: Behrendt Frank , Rizza Julia Charlotte , Blum Fabian , Suica Zorica , Schuster-Amft Corina
Published: July 2020

Background

The English version of the Chedoke Arm and Hand Activity Inventory is a validated, upper-limb measure with the purpose of assessing functional recovery of the arm and hand after a stroke. A German translation and cross-cultural adaptation was recently produced and demonstrated high validity, inter-rater reliability and internal consistency. As a follow-up, the present study evaluated the intra-rater reliability and responsiveness of the CAHAI-G for the long and all shortened versions.

Methods

The CAHAI-G and the Action Research Arm Test were assessed on three different measurement events: upon entry (ME1), two to 3 days after entry (ME2), and after three to 4 weeks (ME3). For the intra-rater reliability analysis, the ME1 CAHAI assessments were recorded on video and rated by three therapists to obtain the intraclass coefficients (ICC). The data of all three MEs were analysed in a group of stroke inpatients for the evaluation of responsiveness. To test for responsiveness, the CAHAI-G change data were compared to concurrent instruments: The Global Rating of Change-questionnaire and the Global Rating of Concept-questionnaire. Both served as external criteria. For all CAHAI-G versions (7, 8, 9 or 13 items), the same analysis procedures for the evaluation of the responsiveness parameter were performed.

Results

In total, 27 patients (9 females, age 63 ± 13.7) were enrolled in the study. The ICCs for the intra-rater reliability were calculated to be between 0.988 and 0.998 for all CAHAI versions. Responsiveness parameters were as follows from CAHAI-G 7 to 13: Minimal Detectable Change (MDC90) 5.3, 6.0, 6.1, 8.2; Pearson’s correlation coefficients CAHAI-Gs with ARAT 0.365, 0.409*, 0.500**, 0.597**. The Area und Under the Curve and the Minimal Clinical Important Difference values for all CAHAI-G versions and the three external criteria ranged between 0.483 to 0.603 and 2.5 to 9.0, respectively.

Conclusion

In addition to the high validity, inter-rater reliability and internal consistency, the CAHAI-G revealed high intra-rater reliability. The data also suggest an adequate responsiveness of the CAHAI-G versions 9 and 13.
The importance of primary tumor origin in gastrointestinal malignancies undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Authors: Leigh Natasha , Solomon Daniel , Pletcher Eric , Labow Daniel M. , Magge Deepa R. , Sarpel Umut , Golas Benjamin J.
Published: July 2020

Background

Appendiceal and colorectal cancers with peritoneal carcinomatosis (PC) can derive benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, its role in gastric and small bowel malignancies remains undefined.

Methods

We retrospectively analyzed 251 gastrointestinal adenocarcinomas with PC which underwent CRS/HIPEC at our institution from 2007 to 2017. We compared outcomes of gastric, small bowel, appendiceal, and colorectal cohorts.

Results

Thirty-one gastric, 8 small bowel, 91 appendiceal, and 121 colorectal cohorts were included. More gastric cancers (90%) received neoadjuvant chemotherapy than any other cohort, p = 0.002. Although colorectal had the lowest peritoneal cancer index (PCI) (9) and appendiceal the highest (16), all cohorts underwent similar rates of organ resection and complete cytoreduction. Length of stay (p = 0.005) and major perioperative morbidity (Clavien III/IV, p = 0.011) were significantly higher in gastric and small bowel. Median overall survival (OS, p < 0.001) was significantly shorter in gastric (13 months) and small bowel (9 months) than in appendiceal (33 months) and colorectal (42 months) cohorts. On multivariate analysis, complete cytoreduction and PCI score were significant predictors of OS, p < 0.05.

Conclusions

Primary tumor origin significantly affects outcomes after CRS/HIPEC for gastrointestinal malignancies. Though there was a survival benefit in appendiceal and colorectal, gastric and small bowel survival was comparable to systemic chemotherapy.
Talc pleurodesis versus indwelling pleural catheter among patients with malignant pleural effusion: a meta-analysis of randomized controlled trials
Authors: Wang Li , Deng Huan , Chen Xinling , Li Can , Yi Fengming , Wei Yiping , Zhang Wenxiong
Published: July 2020

Background

Talc pleurodesis (TP) and indwelling pleural catheter (IPC) are used for the management of malignant pleural effusion (MPE). Our meta-analysis was conducted to assess the efficacy and safety of both treatments among patients with MPE.

Methods

We acquired pertinent randomized controlled trials (RCTs) by searching PubMed, ScienceDirect, the Cochrane Library, Scopus, Ovid Medline, Embase, Web of Science, and Google Scholar. The endpoints included survival, pleurodesis rates, total drainage, further pleural interventions, hospital days, symptoms, quality of life (QoL), and complications.

Results

We included four high-quality RCTs. Both treatments were effective among patients with MPE and no previous pleurodesis, with comparable survival and equivalent relief of breathlessness. Additionally, the TP group had higher pleurodesis rates, less total drainage, and fewer all-grade complications (including catheter blockage and cellulitis). However, patients in the TP group had more pleural procedures and relatively longer hospital stays. Additionally, no apparent difference was detected in QoL.

Conclusions

TP has better pleurodesis rates, less total drainage, and fewer all-grade complications. However, TP has more pleural procedures and is not feasible for patients with trapped lungs. IPC has fewer further pleural interventions and shorter hospital stays. However, IPC has the nuisance of long-term in situ draining.
Human follicular fluid shows diverse metabolic profiles at different follicle developmental stages
Authors: Yang Jihong , Feng Ting , Li Suying , Zhang Xinyue , Qian Yun
Published: July 2020

Background

To investigate the metabolic profiles in the follicular fluid (FF) samples from patients undergoing in vitro fertilization (IVF) and to analyze the correlations with follicular development.

Methods

The FF samples were obtained from participants (N = 26) who were receiving IVF under the gonadotropin-releasing hormone agonist (GnRH-a) long protocol stimulation and were collected separately from small (8–13 mm) and large (17–22 mm) follicles at the time of oocyte retrieval. Metabolomic analysis of the FF samples was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results

The results demonstrated that the size of the follicle influences the metabolic signature of the FF according to the profile and differential metabolites. Dehydroepiandrosterone (DHEA), which is enriched in steroid hormone biosynthesis, correlated negatively with the oocyte maturation rate and the high-quality embryo rate, and thus could be used to estimate the predictive diagnostic potential of follicular development.

Conclusion

The FF has different metabolic characteristics in different stages of follicular development. Exploring meaningful metabolites could predict follicular development, and modifications of these metabolites could influence follicular development.