bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of nivolumab for advanced gastric cancer patients with poor performance statuses
Authors: Matsumoto Toshihiko , Yamamoto Yosuke , Kuriona Yusuke , Okazaki Ukyo , Kimura Shogo , Miura Kou , Tsuduki Takao , Watanabe Takanori , Mastumoto Yusuke , Takatani Masahiro
Published: July 2020

Background

Nivolumab has changed the treatment of advanced gastric cancer (AGC). Nivolumab shows better outcomes compared to best supportive care among AGC patients who received at least two prior regimens. However, there are no reliable data regarding AGC patients with poor performance status (PS) who received nivolumab. We investigated the efficacy and safety of nivolumab among AGC patients with poor PS.

Methods

We retrospectively collected clinicopathologic data from patients with AGC who underwent nivolumab monotherapy at our institution from October 2017 to June 2019.

Results

Forty-nine AGC patients who received nivolumab were assessed. Twenty-seven patients had PS 0 or 1 (Good group) and 22 had PS 2 or 3 (Poor group). The median progression-free survival and overall survival durations were 2.0 and 6.0 months in the Good group, respectively, and 1.2 and 2.8 months in the Poor group, respectively. The overall survival was significantly shorter in the Poor group (6.0 vs 2.8 months, p = 0.0255). The disease control rates were 23 and 9% in the Good and Poor groups, respectively. Thirty-three percent of patients experienced immune-related adverse events in the Good group, and 18% in the Poor group.

Conclusion

Nivolumab is feasible but insufficient as third- or later-line treatment for AGC patients with poor PS.
Intrinsic patient factors predictive of inpatient rehabilitation facility discharge following primary total knee arthroplasty: a systematic review and meta-analysis
Authors: Sattler Larissa , Hing Wayne , Rathbone Evelyne , Vertullo Christopher
Published: July 2020

Background

Total Knee Arthroplasty (TKA) reduces pain and improves function in those suffering from severe osteoarthritis. A significant cost of TKA is post-acute care, however, current evidence suggests that discharge to an Inpatient Rehabilitation Facility (IRF) has inferior outcomes to home discharge, with no greater benefit in physical function. Only individual studies have investigated TKA patient characteristics predictive of discharge destination, therefore, the aim is to systematically review the literature and meta-analyse intrinsic patient factors predictive of IRF discharge. If predictive factors are known, then early discharge planning and intervention strategies could be implemented.

Methods

Databases PubMed, CINAHL, Embase, Cochrane, and Pedro were searched up to October 2019 for all studies investigating pre-operative intrinsic patient factors predictive of IRF discharge. For assessing the methodological quality of included studies, the Quality In Prognosis Studies (QUIPS) tool was used. Statistical analysis and graphical reporting were conducted in R statistical software. To assess the effect of predictors of discharge destination, odds ratios with the corresponding 95%CI were extracted from the results of univariate and multivariable analyses.

Results

A total of 9 articles published between 2011 to 2018 with 218,151 TKA patients were included. Of the 13 intrinsic patient factors reported, 6 met the criteria for synthesised review: age, obesity, comorbidity, gender, SF-12/VR-12 survey, and smoking. Due to the heterogeneity of statistical analysis and reporting 2 variables could undergo meta-analysis, gender and smoking. Female gender increased the likelihood of IRF discharge by 78% (OR = 1.78; 95%CI = 1.43–2.20; I2 = 33.3%), however, the relationship between smoking status and discharge destination was less certain (OR = 0.80; 95%CI = 0.42–1.50; I2 = 68.5%).

Conclusion

In this systematic literature review and meta-analysis female gender was shown to be predictive of IRF discharge after total knee arthroplasty. There was also a trend for those of older age and increased comorbidity, as measured by the Charlson Comorbidity Index, or the severely obese to have an increased likelihood of IRF discharge. The marked heterogeneity of statistical methods and reporting in existing literature made pooled analysis challenging for intrinsic patient factors predictive of IRF discharge after TKA. Further, high quality studies of prospective design on predictive factors are warranted, to enable early discharge planning and optimise resource allocation on post-acute care following TKA.

Trial registration

This review was registered with PROSPERO (CRD42019134422).
Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study
Authors: Aasbrenn Martin , Lydersen Stian , Farup Per G
Published: July 2020

Background

Zonulin is a biomarker of impaired intestinal permeability, which has been associated with various disorders. The primary aim was to study serum zonulin (s-zonulin) in individuals with morbid obesity before and after a conservative weight loss intervention followed by bariatric surgery. The secondary aims were to explore predictors of s-zonulin, and the associations between the changes of the predictors and changes in s-zonulin, and to compare the associations in the two treatment periods.

Methods

Individuals with morbid obesity were included. Data before any weight loss interventions, after a 6 months’ conservative weight loss intervention, and 6 months after bariatric surgery were used. S-zonulin was measured with an ELISA method from Immundiagnostik AB, Bensheim, Germany. Data were analysed with mixed models.

Results

The mean body mass index was 42.1 kg/m2 (SD 3.8) at inclusion and was reduced to 38.7 kg/m2 (SD 3.8) and 29.8 kg/m2 (SD 3.8) after the conservative treatment and bariatric surgery respectively. S-zonulin was 63 ng/mL (SD 32) at inclusion and was reduced with 19 ng/ml (95% CI 12 to 26, p < 0.001) after conservative treatment and 11 ng/ml (95% CI 0 to 21, p = 0.04) after bariatric surgery. At inclusion, s-zonulin was significantly associated with factors including p-glucose (B = 2.21, 95% CI 1.09 to 3.33, p < 0.001), c-reactive protein (B = 1.02, 95% CI 0.45 to 1.58, p < 0.001) and the intake of proteins (B = 0.23, 95% CI 0.08 to 0.38, p = 0.003) and non-nutritive sweeteners (B = 0.68, 95% CI 0.19 to 1.17, p = 0.007). The reduction in s-zonulin after the conservative weight loss intervention was significantly associated with improvement in diarrhoea (B = 6.6, 95% CI  1.3 to 11.8, p = 0.02), HbA1c (B = 9.7, 95% CI 1.1 to 18.3, p = 0.03), p-glucose (B = 3.5, 95% CI 1.2 to 5.9, p = 0.004) and gamma-GT (B = 0.28, 95% CI 0.09 to 0.47, p = 0.004), but not associated with the change in body mass index (B = 0.9, 95% CI − 1.5 to 3.3, p = 0.46).

Conclusions

S-zonulin was markedly reduced after the conservative weight loss intervention, and further reduced after bariatric surgery. The reduction in s-zonulin was associated with improvement of diarrhoea, markers of glucose intolerance and liver disease, but not associated with the change in body mass index.
Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population
Authors: Rivera-León Edgar Alfonso , Llamas-Covarrubias Mara Anaís , Sánchez-Enríquez Sergio , Martínez-López Erika , González-Hita Mercedes , Llamas-Covarrubias Iris Monserrat
Published: July 2020

Background

Type 2 diabetes mellitus (T2D) is the most frequent type of diabetes. It has a multifactorial etiology, affecting millions of people worldwide. Ghrelin gene (GHRL) encodes the ghrelin peptide, which promotes food intake, induces body weight and adipogenesis. Several single nucleotide polymorphisms (SNPs) in GHRL gene have been associated with metabolic diseases. A protective effect of the Leu72Met (rs696217) polymorphism has been described for T2D in some populations, but this effect seems to depend on the ethnicity of the patients studied.

Methods

The aim of this study was to investigate the association between the GHRL Leu72Met (rs696217) SNP with the development of T2D and serum ghrelin levels in a Western Mexican population. We performed a case-control study in which we included 284 subjects (159 with previous T2D diagnosis and 125 control subjects (CS)). Leu72Met SNP was genotyped by using PCR-RFLPs technique. Serum ghrelin levels were measured using a commercial enzyme immunoassay. Genotypic and allelic distributions were compared using Chi square test. Student T-test and Mann-Whitney U test were used to compare quantitative variables. Odds ratio (OR) was used to evaluate the association between alleles or genotypes and T2D. Multiple and logistic regression models were performed for adjustment. A two-tailed p-value ≤0.05 was considered statistically significant.

Results

Leu72Leu genotype was more frequent among T2D compared to CS (p < 0.05). After adjusting for age and body composition, there was a significant protective effect of the 72Met allele for T2D development (OR 0.40 IC 95% 0.23–0.70; p ≤ 0.001). Fasting serum ghrelin levels were lower in T2D than CS (p ≤ 0.0001) irrespective of age, body weight and BMI. No associations were found between genotypes and ghrelin serum levels in our population.

Conclusions

The GHRL 72Met allele decreases susceptibility for T2D development in a Western Mexican population. Serum ghrelin levels are lower in T2D independently of Leu72Met polymorphism genotype.
Epidemiology of orthodontic treatment need in southwestern Ethiopian children: a cross sectional study using the index of orthodontic treatment need
Authors: Tolessa Mulualem , Singel Amit T. , Merga Hailu
Published: July 2020

Background

The planning of orthodontic treatment within a public health system requires information on the orthodontic treatment needs of the population. It is important to have epidemiological data to estimate the total need for orthodontic care in any region. The present study aimed to determine the orthodontic treatment need in 12 years old Southwestern Ethiopian children.

Methods

The institution-based cross-sectional study was conducted which involved 347 twelve years old school children randomly selected from seven different public schools in Jimma Town, Southwestern Ethiopia. A structured interview and clinical examination were used to assess the subjects. One examiner used Dental Health Component (DHC) and Aesthetic Component (AC) of the Index of Orthodontic Treatment Need (IOTN) to estimate the treatment need. Descriptive statistics and chi-square tests were used for data analysis with statistical significance set at P < 0.05.

Results

According to the DHC of IOTN, almost half of the subjects in the sample were in moderate to the great need for orthodontic treatment. About 15% of the children had a great need for orthodontic treatment based on IOTN-AC. The most prevalent occlusal traits for defining the DHC categorization include increased Overjet (30.8%) and Crowding (23.3%). There was no statistical difference in the distribution of DHC grades and AC scored based on gender.

Conclusion

This study revealed that the need for orthodontic treatment was high. The percentage of the need for orthodontic treatment is higher in comparison to most of the studies conducted in African regions. Therefore, publicly subsidized orthodontic treatment should be planned and provided to those who are in great need for orthodontic treatment. Besides, awareness about orthodontic treatment should also be considered.
Factors influencing the integration of a palliative approach in intensive care units: a systematic mixed-methods review
Authors: Hamdan Alshehri Hanan , Olausson Sepideh , Öhlén Joakim , Wolf Axel
Published: July 2020

Background

While a palliative approach is generally perceived to be an integral part of the intensive care unit (ICU), the provision of palliative care in this setting is challenging. This review aims to identify factors (barriers and facilitators) influencing a palliative approach in intensive care settings, as perceived by health care professionals.

Method

A systematic mixed-methods review was conducted. Multiple electronic databases were used, and the following search terms were utilized: implementation, palliative care, and intensive care unit. In total, 1843 articles were screened, of which 24 met the research inclusion/exclusion criteria. A thematic synthesis method was used for both qualitative and quantitative studies.

Results

Four key prerequisite factors were identified: (a) organizational structure in facilitating policies, unappropriated resources, multi-disciplinary team involvement, and knowledge and skills; (b) work environment, including physical and psychosocial factors; (c) interpersonal factors/barriers, including family and patients’ involvement in communication and participation; and (d) decision-making, e.g., decision and transition, goal conflict, multidisciplinary team communication, and prognostication.

Conclusion

Factors hindering the integration of a palliative approach in an intensive care context constitute a complex interplay among organizational structure, the care environment and clinicians’ perceptions and attitudes. While patient and family involvement was identified as an important facilitator of palliative care, it was also recognized as a barrier for clinicians due to challenges in shared goal setting and communication.
Self-regulated learning microanalysis for the study of the performance of clinical examinations by physiotherapy students
Authors: Medina-Ramírez Raquel I. , Álamo-Arce D. David , Rodriguez-Castro Felipe , Cecilio-Fernandes Dario , Sandars John , Costa Manuel J.
Published: July 2020

Background

Students require feedback on their self-regulated learning (SRL) processes to improve the performance of clinical examinations. The key SRL processes used by students can be identified by SRL-micro-analysis but, this method has not been previously applied to physiotherapy students. The aim of this pilot study was to test a research design that might allow the evaluation of the potential usefulness of SRL microanalysis for the identification of key SRL processes used by physiotherapy students during the performance of a clinical examination skill. The objectives of the pilot study were: 1) to evaluate whether SRL-microanalysis could identify differences in the use of SRL processes between successful and unsuccessful students; 2) to evaluate the reliability of SRL microanalysis ratings produced by different assessors.

Methods

SRL-microanalysis was used with second year physiotherapy students of a Spanish university (n = 26) as they performed a goniometric task. The task required students to obtain a goniometric measurement of the shoulder joint of a peer. Two assessors evaluated student performance and conducted the SRL- microanalysis with all students. An analysis of inter-rater reliability was performed to evaluate the degree of agreement between assessors.

Results

The SRL-microanalysis revealed differences in the use of key SRL processes between successful (n = 15: 57.0%) and unsuccessful performers (n = 11: 43.0%): The differences were particularly evident in strategic planning and self-monitoring skills. There was good inter-rater reliability for scoring of strategic planning (k = 0.792), self-monitoring (k = 0.946) and self-evaluation (k = 0.846).

Conclusion

The use of SRL microanalysis characterized the key SRL processes of physiotherapy students performing a clinical skill with reliability between the assessors. This pilot study supports the potential usefulness of SRL-microanalysis for the identification of key SRL processes in physiotherapy education. Therefore, this study paves the way to the development of a full study, with a larger number of students and more diverse clinical tasks, to evaluate the SRL processes in successful and unsuccessful students.
The association between Asian patient race/ethnicity and lower satisfaction scores
Authors: Liao Lillian , Chung Sukyung , Altamirano Jonathan , Garcia Luis , Fassiotto Magali , Maldonado Bonnie , Heidenreich Paul , Palaniappan Latha
Published: July 2020

Background

Patient satisfaction is increasingly being used to assess, and financially reward, provider performance. Previous studies suggest that race/ethnicity (R/E) may impact satisfaction, yet few practices adjust for patient R/E. The objective of this study is to examine R/E differences in patient satisfaction ratings and how these differences impact provider rankings.

Methods

Patient satisfaction survey data linked to electronic health records from two large outpatient centers in northern California – a non-profit organization of community-based clinics (Site A) and an academic medical center (Site B) – was collected and analyzed. Participants consisted of adult patients who received outpatient care at Site A from December 2010 to November 2014 and Site B from March 2013 to August 2014, and completed Press-Ganey Medical Practice Survey questionnaires (N = 216,392 (Site A) and 30,690 (Site B)). Self-reported non-Hispanic white (NHW), Black, Latino, and Asian patients were studied. For six questions each representing a survey subdomain, favorable ratings were defined as top-box (“very good”) compared to all other categories (“very poor,” “poor,” “fair,” and “good”). Using multivariable logistic regression with provider random effects, we assessed whether the likelihood of giving favorable ratings differed by patient R/E, adjusting for patient age and sex.

Results

Asian, younger and female patients provided less favorable ratings than other R/E, older and male patients. After adjustment, Asian patients were less likely than NHW patients to provide top-box ratings to the overall assessment question “likelihood of recommending this practice to others” (Site A: Asian predicted probability (PP) 0.680, 95% confidence interval (CI): 0.675–0.685 compared to NHW PP 0.820, 95% CI: 0.818–0.822; Site B: Asian PP 0.734, 95% CI: 0.733–0.736 compared to NHW PP 0.859, 95% CI: 0.859–0.859). The effect sizes for Asian R/E were greater than the effect sizes for older age and female sex. An absolute 3% decrease in mean composite score between providers serving different percentages of Asian patients translated to an absolute 40% drop in national ranking.

Conclusions

Patient satisfaction scores may need to be adjusted for patient R/E, particularly for providers caring for high panel percentages of Asian patients.
Bringing women’s voices to PMTCT CARE: adapting CARE’s Community Score Card© to engage women living with HIV to build quality health systems in Malawi
Authors: Laterra Anne , Callahan Tegan , Msiska Thumbiko , Woelk Godfrey , Chowdhary Pari , Gullo Sara , Mwale Patience Mgoli , Modi Surbhi , Chauwa Felluna , Kayira Dumbani , Kalua Thokozani , Wako Etobssie
Published: July 2020

Background

Coverage of prevention of mother-to-child transmission of HIV (PMTCT) services has expanded rapidly but approaches to ensure service delivery is patient-centered have not always kept pace. To better understand how the inclusion of women living with HIV in a collective, quality improvement process could address persistent gaps, we adapted a social accountability approach, CARE’s Community Score Card© (CSC), to the PMTCT context. The CSC process generates perception-based score cards and facilitates regular quality improvement dialogues between service users and service providers.

Methods

Fifteen indicators were generated by PMTCT service users and providers as part of the CSC process. These indicators were scored by each population during three sequential cycles of the CSC process which culminates in a sharing of scores in a collective meeting followed by action planning. We aggregated these scores across facilities and analyzed the differences in first and last scorings to understand perceived improvements over the course of the project (z-test comparing the significance of two proportions; one-tailedp-value ≤ .05). Data were collected over 12 months from September 2017 to August 2018.

Results

Fourteen of the fifteen indicators improved over the course of this project, with eight showing statistically significant improvement. Out of the indicators that showed statistically significant improvement, the majority fell within the control of local communities, local health facilities, or service providers (7 out of 8) and were related to patient or user experience and support from families and community members (6 out of 8). From first to last cycle, scores from service users’ and service providers’ perspectives converged. At the first scoring cycle, four indicators exhibited statistically significant differences (p-value ≤ .05) between service users and service providers. At the final cycle there were no statistically significant differences between the scores of these two groups.

Conclusions

By creating an opportunity for mothers living with HIV, health service providers, communities, and local government officials to jointly identify issues and implement solutions, the CSC contributed to improvements in the perceived quality of PMTCT services. The success of this model highlights the feasibility and importance of involving people living with HIV in quality improvement and assurance efforts.

Trial registration

Trial registration: ClincalTrials.govNCT04372667retrospectively registered on May 1st 2020.
The role of local and regional authorities in prevention and control of NCDs: the case of Poland
Authors: Tabaszewski Robert
Published: July 2020

Background

Freedom from noncommunicable diseases is a component of the human right to health. The obligation to reduce the pandemic of civilisation diseases should result from the provisions of the constitution, national law and local regulations. This means that representatives of local and regional communities also take responsibility for limiting the pandemic of civilisation diseases.

Main body

The goal of this debate is to examine the effectiveness of the decentralised polish model for dividing the competences of preventing and combating non-communicable diseases into three levels: local, regional and central. The representatives of regional and local communities are responsible for encouraging the inhabitants of their communities to change their lifestyle: eating habits, increase physical activity, remain outdoors more frequently, reduce stimulants, and apply prevention, namely undergo regular medical check-ups and provide the body with all the necessary nutrients. Limiting the proliferation of noncommunicable diseases also requires, in vertical terms, sound financial efforts on the part of local authorities. In the example of Poland, the claim about the effectiveness of the multi-level governance model which is presented in the literature will be verified.

Conclusion

The excessive division of competences and the dispersion of resources between regional and local authorities may hamper the effective treatment and prevention of NCDs. A lack of cooperation between the central government, which carries out an independent policy on public health, and local authorities, which use only a portion of the public funds allocated to health, obstructs the debate on priorities at the societal level and does not encourage residents to take a stand on how to allocate extra funds.
Treating type 2 diabetes in COVID-19 patients: the potential benefits of injective therapies
Authors: Longo Miriam , Caruso Paola , Maiorino Maria Ida , Bellastella Giuseppe , Giugliano Dario , Esposito Katherine
Published: July 2020

The coronavirus disease 2019 (COVID-19) has been declared as pandemic by the World Health Organization and is causing substantial morbidity and mortality all over the world. Type 2 diabetes, hypertension, and cardiovascular disease significantly increase the risk for hospitalization and death in COVID-19 patients. Hypoglycemia and hyperglycemia are both predictors for adverse outcomes in hospitalized patients. An optimized glycemic control should be pursued in patients with diabetes and SARS-CoV-2 infection in order to reduce the risk of severe COVID-19 course. Both insulin and GLP-1RAs have shown optimal glucose-lowering and anti-inflammatory effects in type 2 diabetic patients and may represent a valid therapeutic option to treat asymptomatic and non-critically ill COVID-19 diabetic patients.
Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
Authors: Gao Yisheng , Liu Jie , Huan Jing , Che Fengyuan
Published: July 2020

Background

One of the main reasons for the failure of prostate cancer (PCa) treatment is the generation of chemoresistance. Circular RNA hsa_circ_0000735 (hsa_circ_0000735) is connected with the progression of cancer. Nevertheless, the role and regulatory mechanism of hsa_circ_0000735 in the resistance of PCa to docetaxel (DTX) are unclear.

Methods

Expression levels of hsa_circ_0000735 and miR-7-5p (miR-7) in tissue samples and cells were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The DTX sensitivity, viability, colony formation, cell cycle progression, and apoptosis of DTX-resistant PCa cells were determined via Cell Counting Kit-8 (CCK-8), cell colony formation, or flow cytometry assays. The levels of multidrug resistance protein 1 (MDR1) protein, cyclinD1, and B cell lymphoma 2 (bcl-2) were detected by western blotting. The interaction between hsa_circ_0000735 and miR-7 was verified via dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The role of hsa_circ_0000735 in vivo was validated through tumor formation experiments.

Results

Hsa_circ_0000735 was upregulated and miR-7 was downregulated in DTX-resistant PCa tissues and cells. High hsa_circ_0000735 expression had a shorter overall survival. Both hsa_circ_0000735 knockdown and miR-7 mimic boosted DTX sensitivity, constrained viability, colony formation, cell cycle progression, and fostered apoptosis of DTX-resistant PCa cells. Also, hsa_circ_0000735 silencing elevated DTX sensitivity and repressed tumor growth in PCa in vivo. Mechanistically, hsa_circ_0000735 served as a sponge for miR-7. MiR-7 inhibition overturned hsa_circ_0000735 silencing-mediated impacts on DTX sensitivity and the malignant behaviors of DTX-resistant PCa cells.

Conclusion

Hsa_circ_0000735 downregulation boosted PCa sensitivity to DTX and reduced tumor growth via sponging miR-7, providing a promising prognostic biomarker and therapeutic target for PCa.
Cross-sectional validity and specificity of comprehensive measurement in lymphedema and lipedema of the lower extremity: a comparison of five outcome instruments
Authors: Angst Felix , Lehmann Susanne , Aeschlimann André , Sandòr Peter S. , Wagner Stephan
Published: July 2020

Background

Literature on the validity of outcome measurement in lymphedema and lipedema is very sparse. This study aimed to examine the convergent, divergent and discriminant validity of a set of 5 instruments in both conditions.

Methods

Cross-sectional outcome was measured by the generic Short Form 36 (SF-36), the lymphedema-specific Freiburg Quality of Life Assessment for lymphatic disorders, Short Version (FLQA-lk), the knee-specific Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), the Symptom Checklist-90-revised (SCL-90R), and the Six-Minute Walk Test (6 MWT). Construct convergent/divergent validity was quantified by bivariate correlations and multivariate factor analysis, and discriminant validity by standardized mean differences (SMDs).

Results

Health was consistently better in lymphedema (n = 107) than in lipedema (n = 96). The highest construct convergence was found for physical health between the SF-36 and KOS-ADL (bivariate correlations up to 0.78, factor loads up to 0.85, explained variance up to 56.8%). The second most important factor was mental health (bivariate correlations up to 0.79, factor loads up to 0.86, explained variance up to 13.3%). Discriminant validity was greatest for the FLQA-lk Physical complaints (adjusted SMD = 0.93) followed by the SF-36 Bodily pain (adjusted SMD = 0.83), KOS-ADL Function (adjusted SMD = 0.47) and SF-36 Vitality (adjusted SMD = 0.39).

Conclusions

All five instruments have specific strengths and can be implemented according to the scope and aim of the outcome examination. A minimum measurement set should comprise: the SF-36 Bodily pain, SF-36 Vitality, FLQA-lk Physical complaints, FLQA-lk Social life, FLQA-lk Emotional well-being, FLQA-lk Health state, KOS-ADL Symptoms, KOS-ADL Function, and the SCL-90R Interpersonal sensitivity.
Efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of malignant ascites
Authors: Jiao Jie , Li Chengzhen , Yu Guanying , Zhang Lei , Shi Xiaoyan , Yan Jingdu , Zhang Houjun , Guo Peiming
Published: July 2020

Objective

The purpose of this study is to compare the difference of clinical efficacy between conventional intraperitoneal chemotherapy and HIPEC, so as to explore the clinical application value and advantages of HIPEC.

Design

A retrospective analysis was conducted on 80 patients with malignant ascites admitted to our hospital from June 2017 to June 2019. The general clinical data and qualitative data of the treatment results of 80 patients with malignant ascites were processed by SPSS19.0 using χ2 test, and quantitative data were processed by t test. P < 0.05, statistical data can be considered statistically significant.

Results

There was no significant change in vital signs and temperature in the observation group during the treatment, and the difference was not statistically significant.

The short-term total effective rate of patients in the observation group was 91.11%, and the short-term total effective rate of the patients in the control group was 40%.

There was no significant difference in the incidence of adverse reactions between the two groups of patients.

Conclusion

Intraperitoneal hyperthermic chemotherapy combined with intravenous chemotherapy can significantly control malignant ascites and has small adverse reactions, which is worthy of clinical promotion and application.
Whole genomic analysis of a potential recombinant human adenovirus type 1 in Qinghai plateau, China
Authors: Yu Juan , Zhao Shengcang , Rao Huaxiang
Published: July 2020

Human adenoviruses (HAdVs) are prevalent in patients with respiratory infections, in which recombination has important implications for viral detection and pathogenicity. However, less HAdVs recombination was reported in Qinghai plateau. In this study, we obtained an HAdV-C strain (QH-1665/2018) isolated from an infant aged one month with influenza-like illness in Qinghai Province in 2018. The whole genome sequence was generated by next-generation sequencing, and compared with that of other HAdV-C strains available in public. The strain QH-1665/2018 genome is comprised of 36,014 nucleotides and encoded 36 putative proteins. Phylogenetic analysis of complete HAdV genomes and 3 major antigen genes (penton, hexon and fiber) showed that strain QH-1665/2018 was clustered into HAdV-1 [P1H1F1]. Recombination analysis based on the RDP4 package and SimPlot software showed that QH-1665/2018 was a recombinant involving HAdV-1, HAdV-2 and HAdV-5, which was then re-confirmed by phylogenetic analysis. Our results suggest that HAdV-C recombination is highly complex, should be focused on, and the epidemiological and virological surveillance should be strengthened in Qinghai Province.
Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1
Authors: Zhang Yuhui , Huang Weibin , Yuan Yujie , Li Jin , Wu Jing , Yu Jie , He Yulong , Wei Zhewei , Zhang Changhua
Published: July 2020

Background

Long non-coding RNA H19 was demonstrated to be significantly correlated with tumor metastasis. However, the specific functions of H19 in colorectal cancer (CRC) metastasis and the underlying mechanism are still largely unclear.

Methods

Use public database to screen the potential lncRNA crucial for metastasis in colorectal cancer. The expression of H19 in clinical CRC specimens was detected by qRT-PCR. The effect of H19 on the metastasis of CRC cells was investigated by transwell, wound healing assays, CCK-8 assays and animal studies. The potential proteins binding to H19 were identified by LC-MS and verified by RNA immunoprecipitation (RIP). The expression of indicated RNA and proteins were measured by qRT-PCR or western blot.

Results

We found the expression of lncRNA H19 was significantly upregulated in primary tumor and metastatic tissues, correlated with poor prognosis in CRC. Ectopic H19 expression promoted the metastasis of colorectal cancer cells in vitro and in vivo, and induced epithelial-to-mesenchymal transition (EMT). Mechanistically, H19 directly bound to hnRNPA2B1. Knockdown of hnRNPA2B1 attenuated the H19-induce migration and invasion in CRC cells. Furthermore, H19 stabilized and upregulated the expression of Raf-1 by facilitated the interaction between hnRNPA2B1 and Raf-1 mRNA, resulting in activation of Raf-ERK signaling.

Conclusions

Our findings demonstrate the role of H19/hnRNPA2B1/EMT axis in regulation CRC metastasis, suggested H19 could be a potential biomarker to predict prognosis as well as a therapeutic strategy for CRC.
Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence
Authors: van Haren Frank M. P. , Page Clive , Laffey John G. , Artigas Antonio , Camprubi-Rimblas Marta , Nunes Quentin , Smith Roger , Shute Janis , Carroll Mary , Tree Julia , Carroll Miles , Singh Dave , Wilkinson Tom , Dixon Barry
Published: July 2020

Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.

The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.

These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.
Automated vs. conventional ventilation in the ICU: a randomized controlled crossover trial comparing blood oxygen saturation during daily nursing procedures (I-NURSING)
Authors: Chelly Jonathan , Mazerand Sandie , Jochmans Sebastien , Weyer Claire-Marie , Pourcine Franck , Ellrodt Olivier , Thieulot-Rolin Nathalie , Serbource-Goguel Jean , Sy Oumar , Vong Ly Van Phach , Monchi Mehran
Published: July 2020

Background

Hypoxia is common during daily nursing procedures (DNPs) routinely performed on mechanically ventilated patients. The impact of automated ventilation on the incidence and severity of blood oxygen desaturation during DNPs remains unknown.

Methods

A prospective randomized controlled crossover trial was carried out in a French intensive care unit to compare blood oxygen pulse saturation (SpO2) during DNPs performed on patients mechanically ventilated in automated and conventional ventilation modes (AV and CV, respectively). All patients with FiO2 ≤ 60% and without prone positioning or neuromuscular blocking agents were included. Patients underwent two DNPs on the same day using AV (INTELLiVENT-ASV®) and CV (volume control, biphasic positive airway pressure, or pressure support ventilation) in a randomized order. The primary outcome was the percentage of time spent with SpO2 in the acceptable range of 90–95% during the DNP.

Results

Of the 265 included patients, 93% had been admitted for a medical pathology, the majority for acute respiratory failure (52%). There was no difference between the two periods in terms of DNP duration, sedation requirements, or ventilation parameters, but patients had more spontaneous breaths and lower peak airway pressures during the AV period (p <  0.001). The percentage of time spent with SpO2 in the acceptable range during DNPs was longer in the AV period than in the CV period (48 ± 37 vs. 43 ± 37, percentage of DNP period; p = 0.03). After adjustment, AV was associated with a higher number of DNPs carried out with SpO2 in the acceptable range (odds ratio, 1.82; 95% CI, 1.28 to 2.6; p = 0.001) and a lower incidence of blood oxygen desaturation ≤ 85% (adjusted odds ratio, 0.50; 95% CI, 0.30 to 0.85; p = 0.01).

Conclusion

AV appears to reduce the incidence and severity of blood oxygen desaturation during daily nursing procedures (DNPs) in comparison to CV.

Trial registration

This study was registered in clinical-trial.gov (NCT03176329) in June 2017.

Graphical abstract
Erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers and fatty acid synthase: a nested case-control study
Authors: McGee Emma E. , Kim Claire H. , Wang Molin , Spiegelman Donna , Stover Daniel G. , Heng Yujing J. , Collins Laura C. , Baker Gabrielle M. , Farvid Maryam S. , Schedin Pepper , Jindal Sonali , Tamimi Rulla M. , Eliassen A. Heather
Published: July 2020

Background

Previous studies of fatty acids and breast cancer risk have shown mixed results, which may be due in part to tumor heterogeneity. Prior research has also illustrated an important role of specific fatty acids in immune regulation, T cell function, and inflammation, indicating that the effects of specific fatty acids on breast cancer risk may vary by tumor expression of immuno-inflammatory markers. We therefore aimed to evaluate the relationships between prediagnostic erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers (CD4, CD8, CD20, CD163, COX-2) and fatty acid synthase (FAS).

Methods

We conducted a matched case-control study nested within the Nurses’ Health Study II (n = 235 cases and 235 controls). Blood samples were collected from 1996 to 1999. Tumor tissue blocks were collected for cases diagnosed after blood collection and through 2006. Unconditional nominal polytomous logistic regression adjusted for matching factors and potential confounders was used to assess whether associations between fatty acids and breast cancer risk varied by tumor expression subtype, ascertained via immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated separately by tumor expression subtype using unconditional logistic regression.

Results

Associations between fatty acids and breast cancer risk did not vary substantially by tumor CD4, CD20, CD163, or COX-2. However, n-3 polyunsaturated fatty acids (PUFAs) were inversely associated with CD8low but not CD8high cancers (CD8low ORT3 vs T1 = 0.45, 95% CI 0.23–0.87, Ptrend = 0.02; CD8high ORT3 vs T1 = 1.19, 95% CI 0.62–2.26, Ptrend = 0.62; Phet = 0.04). n-6 PUFAs were suggestively inversely associated with CD8high but not CD8low cancers (CD8high ORT3 vs T1 = 0.61, 95% CI 0.32–1.14, Ptrend = 0.11; CD8low ORT3 vs T1 = 1.63, 95% CI 0.87–3.04, Ptrend = 0.12; Phet = 0.02). Trans fatty acids were positively associated with FAShigh but not FASlow tumors (FAShigh ORT3 vs T1 = 2.94, 95% CI 1.46–5.91, Ptrend = 0.002; FASlow ORT3 vs T1 = 0.99, 95% CI 0.52–1.92, Ptrend = 0.97; Phet = 0.01).

Conclusion

Results indicate that the effects of n-3 PUFAs, n-6 PUFAs, and trans fatty acids on breast cancer risk may vary by tumor tissue expression subtypes. Findings suggest potential immuno-modulatory and FAS-mediated mechanisms.
Producing polished prokaryotic pangenomes with the Panaroo pipeline
Authors: Tonkin-Hill Gerry , MacAlasdair Neil , Ruis Christopher , Weimann Aaron , Horesh Gal , Lees John A. , Gladstone Rebecca A. , Lo Stephanie , Beaudoin Christopher , Floto R. Andres , Frost Simon D.W. , Corander Jukka , Bentley Stephen D. , Parkhill Julian
Published: July 2020

Population-level comparisons of prokaryotic genomes must take into account the substantial differences in gene content resulting from horizontal gene transfer, gene duplication and gene loss. However, the automated annotation of prokaryotic genomes is imperfect, and errors due to fragmented assemblies, contamination, diverse gene families and mis-assemblies accumulate over the population, leading to profound consequences when analysing the set of all genes found in a species. Here, we introduce Panaroo, a graph-based pangenome clustering tool that is able to account for many of the sources of error introduced during the annotation of prokaryotic genome assemblies. Panaroo is available at https://github.com/gtonkinhill/panaroo.
Identification and genotyping of Enterocytozoon bieneusi in wild Himalayan marmots (Marmota himalayana) and Alashan ground squirrels (Spermophilus alashanicus) in the Qinghai-Tibetan Plateau area (QTPA) of Gansu Province, China
Authors: Xu Jie , Wang Xin , Jing Huaiqi , Cao Shengkui , Zhang Xiaofan , Jiang Yanyan , Yin Jianhai , Cao Jianping , Shen Yujuan
Published: July 2020

Background

Enterocytozoon bieneusiis the most frequently detected microsporidian species in humans and animals. Currently, to the best of our knowledge, no information onE. bieneusiinfection in Himalayan marmots (Marmota himalayana) and Alashan ground squirrels (Spermophilus alashanicus) is available worldwide. The aim of the present study was to understand the occurrence and genetic characterizations ofE. bieneusiin Himalayan marmots and Alashan ground squirrels in the Qinghai-Tibetan Plateau area (QTPA), Gansu Province, China.

Methods

A total of 498 intestinal contents were collected from 399 Himalayan marmots and 99 Alashan ground squirrels in QTPA. These samples were screened for the presence ofE. bieneusiby using nested polymerase chain reaction and sequencing of the internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA) gene. The ITS-positive sequences were aligned and phylogenetically analyzed to determine the genotypes ofE. bieneusi.

Results

The average infection rate ofE. bieneusiwas 10.0% (50/498), with 11.8% (47/399) in Himalayan marmots and 3.0% (3/99) in Alashan ground squirrels. A total of 7 distinctE. bieneusigenotypes were confirmed: 1 known genotype, YAK1 (n = 18) and 6 novel genotypes, named as ZY37 (n = 27), HN39 (n = 1), HN96 (n = 1), SN45 (n = 1), XH47 (n = 1) and ZY83 (n = 1). All the genotypes obtained in the present study were classified into group 1.

Conclusions

To our knowledge, this is the first report ofE. bieneusiin Himalayan marmots and Alashan ground squirrels in China. The identification of genotype YAK1 in the two rodent species expanded the host range of this genotype. All the seven genotypes were clustered into zoonotic group 1, suggesting that these animal species can be potential epidemiological vectors of zoonotic microsporidiosis caused byE. bieneusiand pose a threat to ecological security. It is necessary to strengthen management practices and surveillance in the investigated areas to reduce the risk ofE. bieneusiinfection from the two rodent species to humans.
High insecticide resistances levels in Anopheles gambiaes s.l. in northern Uganda and its relevance for future malaria control
Authors: Echodu Richard , Iga Julius , Oyet William Samuel , Mireji Paul , Anena Juliet , Onanyang David , Iwiru Tereza , Lutwama Julius Julian , Opiyo Elizabeth Auma
Published: July 2020

Objective

The aim of the study was to determine the level of insecticide resistance and diversity inAnopheles mosquitoes in northern Uganda. Standard WHO insecticide susceptibility test assays were used to test for susceptibility to 0.5% malathion, 0.1% bendiocarb, 0.05% deltamethrin and 0.75% permethrin on 3–5 day old generation one progeny. We also screened for species diversity and knockdown resistance using PCR assay.

Results

Anopheles gambiae s.s.is the predominant malaria vector in northern Uganda followed byAn. arabiensis. An. gambiaes.s.was susceptible to malathion and bendiocarb with the observed mortality rate of 100% and 98–100% observed respectively while very high resistance was observed with deltamethrin and permethrin. Minimal KDR-eastern variant homozygous forms of 8.3% inAn. gambiae s.s.were detected in Oyam district. In conclusion, this study confirms thatAn. gambiae s.s.females are susceptible to malathion and bendiocarb while high intensity of resistance was observed with deltamethrin and permethrin in the same area. Use of carbamate and organophosphate insecticides bendiocarb and malathion for indoor residual spraying activities in northern Uganda is highly recommended since high levels of pyrethroids resistance (deltamethrin and permethrin) was detected in the area.
Molecular comparison of pure ovarian fibroma with serous benign ovarian tumours
Authors: Hunter Sally M. , Dall Genevieve V. , Doyle Maria A. , Lupat Richard , Li Jason , Allan Prue , Rowley Simone M. , Bowtell David ,   On behalf of AOCS, Campbell Ian G. , Gorringe Kylie L.
Published: July 2020

Objective

Ovarian fibromas and adenofibromas are rare ovarian tumours. They are benign tumours composed of spindle-like stromal cells (pure fibroma) or a mixture of fibroblast and epithelial components (adenofibroma). We have previously shown that 40% of benign serous ovarian tumours are likely primary fibromas due to the neoplastic alterations being restricted to the stromal compartment of these tumours. We further explore this finding by comparing benign serous tumours to pure fibromas.

Results

Performing copy number aberration (CNA) analysis on the stromal component of 45 benign serous tumours and 8 pure fibromas, we have again shown that trisomy of chromosome 12 is the most common aberration in ovarian fibromas. CNAs were more frequent in the pure fibromas than the benign serous tumours (88% vs 33%), however pure fibromas more frequently harboured more than one CNA event compared with benign serous tumours. As these extra CNA events observed in the pure fibromas were unique to this subset our data indicates a unique tumour evolution. Gene expression analysis on the two cohorts was unable to show gene expression changes that differed based on tumour subtype. Exome analysis did not reveal any recurrently mutated genes.