bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of an e-health readiness assessment framework for developing countries
Authors: Mauco Kabelo Leonard , Scott Richard E. , Mars Maurice
Published: June 2020

Background

Studies document e-health as having potential to improve quality of healthcare services, resulting in both developed and developing countries demonstrating continued interest in e-health uptake and use. e-Health implementations are not always successful as high failure rates have been reported in both developed and developing countries. These failures are often a result of lack of e-health readiness. e-Health readiness has been defined as the preparedness of healthcare institutions or communities for the anticipated change brought by programs related to information and communication technologies. As such it is critical to conduct an e-health readiness assessment prior to implementation of e-health innovations so as to reduce chances of project failure. Noting the absence of an adequate e-health readiness assessment framework (eHRAF) suitable for use in developing countries, the authors conceptualised, designed, and created a developing country specific eHRAF to aid in e-health policy planning. The aim of this study was to validate the developed eHRAF and to determine if it required further refinement before empirical testing.

Methods

Published options for a framework validation process were adopted, and fifteen globally located e-health experts engaged. Botswana experts were engaged using saturation sampling, while international experts were purposively selected. Responses were collated in an Excel spreadsheet, and NVivo 11 software used to aid thematic analysis of the open ended questions.

Results

Analysis of responses showed overall support for the content and format of the proposed eHRAF. Equivocal responses to some open ended questions were recorded, most of which suggested modifications to terms within the framework. One expert from the developed world had alternate views.

Conclusions

The proposed eHRAF provides guidance for e-health policy development and planning by identifying, in an evidence based manner, the major areas to be considered when preparing for an e-health readiness assessment in the context of developing countries.
Programmatic options for monitoring malaria in elimination settings: easy access group surveys to investigate Plasmodium falciparum epidemiology in two regions with differing endemicity in Haiti
Authors: Druetz Thomas , Stresman Gillian , Ashton Ruth A. , van den Hoogen Lotus L. , Joseph Vena , Fayette Carl , Monestime Frank , Hamre Karen E. , Chang Michelle A. , Lemoine Jean F. , Drakeley Chris , Eisele Thomas P.
Published: June 2020

Background

As in most eliminating countries, malaria transmission is highly focal in Haiti. More granular information, including identifying asymptomatic infections, is needed to inform programmatic efforts, monitor intervention effectiveness, and identify remaining foci. Easy access group (EAG) surveys can supplement routine surveillance with more granular information on malaria in a programmatically tractable way. This study assessed how and which type of venue for EAG surveys can improve understanding malaria epidemiology in two regions with different transmission profiles.

Methods

EAG surveys were conducted within the departments of Artibonite and Grand’Anse (Haiti), in regions with different levels of transmission intensity. Surveys were conducted in three venue types: primary schools, health facilities, and churches. The sampling approach varied accordingly. Individuals present at the venues at the time of the survey were eligible whether they presented malaria symptoms or not. The participants completed a questionnaire and were tested for Plasmodium falciparum by a highly sensitive rapid diagnostic test (hsRDT). Factors associated with hsRDT positivity were assessed by negative binomial random-effects regression models.

Results

Overall, 11,029 individuals were sampled across 39 venues in Artibonite and 41 in Grand’Anse. The targeted sample size per venue type (2100 in Artibonite and 2500 in Grand’Anse) was reached except for the churches in Artibonite, where some attendees left the venue before they could be approached or enrolled. Refusal rate and drop-out rate were < 1%. In total, 50/6003 (0.8%) and 355/5026 (7.1%) sampled individuals were hsRDT positive in Artibonite and Grand’Anse, respectively. Over half of all infections in both regions were identified at health facilities. Being male and having a current or reported fever in the previous 2 weeks were consistently identified with increased odds of being hsRDT positive.

Conclusions

Surveys in churches were problematic because of logistical and recruitment issues. However, EAG surveys in health facilities and primary schools provided granular information about malaria burden within two departments in Haiti. The EAG surveys were able to identify residual foci of transmission that were missed by recent national surveys. Non-care seeking and/or asymptomatic malaria infections can be identified in this alternative surveillance tool, facilitating data-driven decision-making for improved targeting of interventions.
Association between the non-HDL-cholesterol-to-HDL-cholesterol ratio and the risk of gallbladder polyp formation among men: a retrospective cohort study
Authors: Zhao Xiaofang , Zheng Huabo , Shan Shengshuai , Wang Kun , Zhang Meng , Xie Songpu , Liu Chengyun
Published: June 2020

Background

Dyslipidaemia and male sex are associated with gallbladder polyp (GBP) formation. However, the potential relation between the non-high-density lipoprotein-cholesterol-to-high-density lipoprotein-cholesterol (non-HDL-c/HDL-c) ratio and GBPs in men is unclear.

Methods

A total of 1866 eligible subjects were selected for this retrospective cohort study from Wuhan Union Hospital between April 1, 2013, and November 30, 2014. Clinical and laboratory data of subjects were collected. Patients with GBPs or cholecystectomy at baseline, with missing data for baseline lipid profiles, following abdominal ultrasonography or taking lipid-lowering drugs were excluded. The patients were divided into five groups based on their non-HDL-c/HDL-c ratios, and descriptive analyses of the baseline data were performed. A Cox proportional hazards model was applied to estimate the relationship between the non-HDL-c/HDL-c ratio and GBPs.

Results

After a median follow-up of 1 year, 7.34% (n = 137) of the subjects developed GBPs. Compared with subjects without GBPs, those who developed GBPs after follow-up had significantly higher triglyceride (TG) levels and non-HDL-c/HDL-c ratios. The prevalence of GBPs showed a linearity increment with age, peaked in the 30–39 years group, 40–49 years group and 50–59 years group, and then declined slightly. The results of univariate analysis showed that the non-HDL-c/HDL-c ratio (hazard ratio (HR) = 1.29, 95% confidence interval (CI), 1.05–1.60, P = 0.0159) was positively correlated with GBPs. In the fully adjusted Cox regression model, the HRs were 2.24 for quintile 2 (95% CI: 1.13–4.44, P = 0.0203), 1.50 for quintile 3 (95% CI: 0.73–3.10, P = 0.269), 2.52 for quintile 4 (95% CI: 1.26–5.01, P = 0.0087) and 2.13 for quintile 5 (95% CI: 1.04–4.37, P = 0.0397). No interaction was found among the subgroups.

Conclusions

A higher non-HDL-c/HDL-c ratio is independently related to a higher risk of GBP formation in Chinese men. Further research is needed to investigate whether this association exists in different regions and races.
Mediating effects of lipids on the association between smoking and coronary artery disease risk among Chinese
Authors: Song Wenjing , Guan Jieqiong , He Pan , Fan Siyu , Zhi Hong , Wang Lina
Published: June 2020

Objective

The mechanism between smoking and coronary artery disease (CAD) remains unclear. It is likely that lipid (including triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C)) have been functioning as one of the mediators between smoking and the CAD occurrence. The study aimed to investigate the mediating effect of lipid on the relationship between smoking and CAD risk.

Methods

The case-control study included 2048 subjects. General linear regression analysis was used to corroborate the association between smoking and lipid levels. Univariate and multivariate logistic regression analysis were performed to reveal the relationship between smoking, lipid and the risk of CAD. Mediation analysis was used to investigate whether the association between smoking and CAD risk was mediated by lipid.

Results

Smoking was found to be associated with the risk of CAD (odds ratio (OR) = 1.34, 95% confidence interval (CI): 1.05–1.71,P = 0.019). Regression analysis showed that TG, TC and HDL-C were associated with CAD (OR = 2.69, 95%CI: 2.12–3.40,P < 0.001; OR = 0.34, 95%CI: 0.29–0.43,P < 0.001; OR = 0.37, 95%CI: 0.30–0.47,P < 0.001). Moreover, the ratio of TG to HDL-C (TG/HDL-C) was also related to CAD (OR = 4.45, 95%CI: 3.52–5.64,P < 0.001). Mediation analysis showed that among the effects of smoking on CAD, 17.52% was mediated by lipid, in which HDL-C accounted for 11.16% and TG accounted for 6.36%. Further analysis showed that the effect was also partially mediated by TG/HDL-C, which was accounted for 28%.

Conclusions

Lipid plays a partial mediation on the association between smoking and CAD risk. The study provides a clue on the mediation effect of lipids on the relationship between smoking and CAD risks, which is a novel insight to the progression of CAD.
Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma
Authors: Lu Chenying , Fang Shiji , Weng Qiaoyou , Lv Xiuling , Meng Miaomiao , Zhu Jinyu , Zheng Liyun , Hu Yumin , Gao Yang , Wu Xulu , Mao Jianting , Tang Bufu , Zhao Zhongwei , Huang Li , Ji Jiansong
Published: June 2020

Background

Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients.

Methods

Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models.

Results

Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvβ3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvβ3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN.

Conclusions

Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC.
ALICE: a randomized placebo-controlled phase II study evaluating atezolizumab combined with immunogenic chemotherapy in patients with metastatic triple-negative breast cancer
Authors: Kyte J. A. , Røssevold A. , Falk R. S. , Naume B.
Published: June 2020

Background

Immunotherapy with checkpoint inhibitors (CI) represents an important novel development in cancer treatment. Metastatic triple-negative breast cancer (mTNBC) is incurable, with a median survival of only ~ 13 months. We have initiated the randomized placebo-controlled phase IIb study ALICE, evaluating PD-L1 blockade combined with immunogenic chemotherapy in mTNBC patients (n = 75). Intriguingly, the host immune response is strongly predictive for the effect of chemotherapy in mTNBC. In the ALICE trial, we release the brake on the immune response by use of atezolizumab, an inhibitory antibody against PD-L1. We utilize anthracyclines, shown to trigger the immune system, and low-dose cyclophosphamide, which has been reported to counter immunosuppressive cells.

Methods

ALICE is a randomized, double-blind, placebo-controlled exploratory phase II study evaluating the safety and efficacy of atezolizumab when combined with immunogenic chemotherapy in subjects with mTNBC. The trial will enroll 75 evaluable subjects, randomized 2:3 into two arms (A:B). The patients receive identical chemotherapy, i.e. pegylated liposomal doxorubicin (PLD 20 mg/m2 intravenously every 2nd week) + cyclophosphamide (50 mg per day, first 2 weeks in each 4 week cycle). Patients in arm A receive placebo, while patients in arm B receive atezolizumab. The primary objectives are assessment of toxicity and progression-free survival. The secondary objectives include overall survival, tumor response rate, clinical benefit rate, patient reported outcomes, biomarkers and assessment of tumor-immune evolution during therapy.

Discussion

The question of how CI should be combined with chemotherapy, is a key challenge facing the field. There is a strong preclinical rationale for exploring if anthracyclines, which are considered to induce immunogenic cell death, synergize with PD-L1 blockade, and if low-dose cyclophosphamide counters tumor tolerance. However, the data from patients is as yet very limited, and the clinical evaluation of these hypotheses is among the key objectives in the ALICE trial. The study includes extensive biobanking and translational sub-projects, also addressing other clinically important questions. These analyses may uncover mechanisms of drug efficacy or tumor resistance, and identify biomarkers allowing personalized therapy. If the trial suggests acceptable safety of the ALICE therapy and provide a signal of clinical efficacy, further studies are warranted.

Trial registration NCT03164993, May 24th 2017; https://clinicaltrials.gov/ct2/show/record/NCT03164993
ENG-releasing subdermal implants in postpartum teenagers – an open-label trial study protocol
Authors: Barbieri M. M. , Juliato C. R. T. , Bahamondes L. , Surita F. G.
Published: June 2020

Background

Higher than expected adolescent pregnancy high rates continue globally, with repeated unplanned pregnancy (UP) in this age group is a public health problem. In Brazil, 16% of pregnancies occur in adolescents under 18 years old, with high maternal morbidity and mortality rates in this age group. Effective and safe contraception is required to reduce UP rates. The objective of our study is to evaluate acceptance of etonogestrel (ENG)-releasing subdermal contraceptive implant after childbirth, before discharge, as well as clinical performance up to one year after placement. Comparison between teenagers who opt for ENG-implant versus other contraceptive methods after childbirth will be also evaluated, specifically regarding UP, continuation and discontinuation rates and reasons, body composition, pelvic ultrasound characteristics and user satisfaction.

Methods

A non-randomized open-label trial will be conducted with teenagers after childbirth and followed up to one year at the Women’s Hospital, University of Campinas (UNICAMP), Campinas, Brazil. The study group will consist of patients who accepted to use ENG-implant and placed before discharge. The comparison group will include adolescents who choose to use other contraceptive methods at the first postpartum visit (42 ± 3 days after childbirth). All women will follow-up at 40–60 days postpartum, as well as, at 6 and 12 months post-enrollment. Patient satisfaction, contraceptive effectiveness, reasons of discontinuation, continuation rate and body composition will be evaluated. Transvaginal ultrasound and electric bio impedance tests will be performed at all follow-up appointments. A 5% significance level was assumed, as well as, a sampling error (absolute) for 10% prevalence. The sample size was calculated at n = 100, obtaining an estimate of 50 to 70 adolescents who would accept the method offered, according to the prevalence and sample error assumed.

Discussion

Long-acting reversible contraceptive (LARC) methods include subdermal implants and intrauterine contraceptives, are considered first line contraception for teenagers. Immediate postpartum use is a safe option, which significantly reduces rates of repeated UP and all the undesirable consequences inherent to this process.

Trial registration

This study was approved by the Ethics and Research Commission of UNICAMP (CAAE: 92869018.5.0000.5404) and the Brazilian Registry of Clinical Trials (REBEC): http://www.ensaiosclinicos.gov.br/rg/RBR-4z7bc6, (number 2.901.752).
A ligation and restriction enzyme independent cloning technique: an alternative to conventional methods for cloning hard-to-clone gene segments in the influenza reverse genetics system
Authors: Bhat Sushant , Bialy Dagmara , Sealy Joshua E. , Sadeyen Jean-Remy , Chang Pengxiang , Iqbal Munir
Published: June 2020

Background

Reverse genetics is used in many laboratories around the world and enables the creation of tailor-made influenza viruses with a desired genotype or phenotype. However, the process is not flawless, and difficulties remain during cloning of influenza gene segments into reverse genetics vectors (pHW2000, pHH21, pCAGGS). Reverse genetics begins with making cDNA copies of influenza gene segments and cloning them into bi-directional (pHW2000) or uni-directional plasmids (pHH21, pCAGGS) followed by transfection of the recombinant plasmid(s) to HEK-293 T or any other suitable cells which are permissive to transfection. However, the presence of internal restriction sites in the gene segments of many field isolates of avian influenza viruses makes the cloning process difficult, if employing conventional methods. Further, the genetic instability of influenza gene-containing plasmids in bacteria (especially Polymerase Basic 2 and Polymerase Basic 1 genes; PB2 and PB1) also leads to erroneous incorporation of bacterial genomic sequences into the influenza gene of interest.

Methods

Herein, we report an easy and efficient ligation and restriction enzyme independent (LREI) cloning method for cloning influenza gene segments into pHW2000 vector. The method involves amplification of megaprimers followed by PCR amplification of megaprimers using a bait plasmid, DpnI digestion and transformation.

Results

Hard-to-clone genes: PB2 of A/chicken/Bangladesh/23527/2014 (H9N2) and PB1 of A/chicken/Bangladesh/23527/2014 (H9N2), A/chicken/Jiangxi/02.05YGYXG023-P/2015 (H5N6) and A/Chicken/Vietnam/H7F-14-BN4–315/2014 (H9N2) were cloned into pHW2000 using our LREI method and recombinant viruses were subsequently rescued.

Conclusion

The LREI cloning procedure represents an alternative strategy for cloning influenza gene segments which have internal restriction sites for the enzymes used in reverse genetics. Further, the problem of genetic instability in bacteria can be alleviated by growing recombinant bacterial cultures at a lower temperature. This technique can be applied to clone any influenza gene segment using universal primers, which would help in rapid generation of influenza viruses and facilitate influenza research and vaccine development.
The platform GrowScreen-Agar enables identification of phenotypic diversity in root and shoot growth traits of agar grown plants
Authors: Nagel Kerstin A. , Lenz Henning , Kastenholz Bernd , Gilmer Frank , Averesch Andreas , Putz Alexander , Heinz Kathrin , Fischbach Andreas , Scharr Hanno , Fiorani Fabio , Walter Achim , Schurr Ulrich
Published: June 2020

Background

Root system architecture and especially its plasticity in acclimation to variable environments play a crucial role in the ability of plants to explore and acquire efficiently soil resources and ensure plant productivity. Non-destructive measurement methods are indispensable to quantify dynamic growth traits. For closing the phenotyping gap, we have developed an automated phenotyping platform,GrowScreen-Agar, for non-destructive characterization of root and shoot traits of plants grown in transparent agar medium.

Results

The phenotyping system is capable to phenotype root systems and correlate them to whole plant development of up to 280Arabidopsisplants within 15 min. The potential of the platform has been demonstrated by quantifying phenotypic differences within 78Arabidopsisaccessions from the 1001 genomes project. The chosen concept ‘plant-to-sensor’ is based on transporting plants to the imaging position, which allows for flexible experimental size and design. As transporting causes mechanical vibrations of plants, we have validated that daily imaging, and consequently, moving plants has negligible influence on plant development. Plants are cultivated in square Petri dishes modified to allow the shoot to grow in the ambient air while the roots grow inside the Petri dish filled with agar. Because it is common practice in the scientific community to growArabidopsisplants completely enclosed in Petri dishes, we compared development of plants that had the shoot inside with that of plants that had the shoot outside the plate. Roots of plants grown completely inside the Petri dish grew 58% slower, produced a 1.8 times higher lateral root density and showed an etiolated shoot whereas plants whose shoot grew outside the plate formed a rosette. In addition, the setup with the shoot growing outside the plate offers the unique option to accurately measure both, leaf and root traits, non-destructively, and treat roots and shoots separately.

Conclusions

Because theGrowScreen-Agarsystem can be moved from one growth chamber to another, plants can be phenotyped under a wide range of environmental conditions including future climate scenarios. In combination with a measurement throughput enabling phenotyping a large set of mutants or accessions, the platform will contribute to the identification of key genes.
Recent trends in stem cell therapy for premature ovarian insufficiency and its therapeutic potential: a review
Authors: Na Jeeyoon , Kim Gi Jin
Published: June 2020

Stem cell therapy is attracting attention in the field of regenerative medicine and is advancing rapidly. Many recent studies have applied stem cell therapy to treat reproductive system diseases; however, data are not yet available as to whether this therapy shows enhanced therapeutic effects. This paper analyzes recent preclinical studies on stem cell therapy for ovarian dysfunction in several types of animal models. Several clinical trials and pending projects are also discussed. This review will provide a background for developing stem cell therapies to enhance ovarian function.
Correction to: The effect of corticosteroids on the mortality of patients with influenza pneumonia: a systematic review and meta-analysis
Authors: Ni Yue-Nan , Chen Guo , Sun Jiankui , Liang Bin-Miao , Liang Zong-An
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
New generation breast cancer cell lines developed from patient-derived xenografts
Authors: Finlay-Schultz Jessica , Jacobsen Britta M. , Riley Duncan , Paul Kiran V. , Turner Scott , Ferreira-Gonzalez Andrea , Harrell J. Chuck , Kabos Peter , Sartorius Carol A.
Published: June 2020

Background

Breast cancer is a highly heterogeneous disease characterized by multiple histologic and molecular subtypes. While a myriad of breast cancer cell lines have been developed over the past 60 years, estrogen receptor alpha (ER)+ disease and some mutations associated with this subtype remain underrepresented. Here we describe six breast cancer cell lines derived from patient-derived xenografts (PDX) and their general characteristics.

Methods

Established breast cancer PDX were processed into cell suspensions and placed into standard 2D cell culture; six emerged into long-term passageable cell lines. Cell lines were assessed for protein expression of common luminal, basal, and mesenchymal markers, growth assessed in response to estrogens and endocrine therapies, and RNA-seq and oncogenomics testing performed to compare relative transcript levels and identify putative oncogenic drivers.

Results

Three cell lines express ER and two are also progesterone receptor (PR) positive; PAM50 subtyping identified one line as luminal A. One of the ER+PR+ lines harbors a D538G mutation in the gene for ER (ESR1), providing a natural model that contains this endocrine-resistant genotype. The third ER+PR−/low cell line has mucinous features, a rare histologic type of breast cancer. The three other lines are ER− and represent two basal-like and a mixed ductal/lobular breast cancer. The cell lines show varied responses to tamoxifen and fulvestrant, and three were demonstrated to regrow tumors in vivo. RNA sequencing confirms all cell lines are human and epithelial. Targeted oncogenomics testing confirmed the noted ESR1 mutation in addition to other mutations (i.e., PIK3CA, BRCA2, CCND1, NF1, TP53, MYC) and amplifications (i.e., FGFR1, FGFR3) frequently found in breast cancers.

Conclusions

These new generation breast cancer cell lines add to the existing repository of breast cancer models, increase the number of ER+ lines, and provide a resource that can be genetically modified for studying several important clinical breast cancer features.
Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors
Authors: Guo Hua , Ding Qingqing , Gong Yun , Gilcrease Michael Z. , Zhao Min , Zhao Jun , Sui Dawen , Wu Yun , Chen Hui , Liu Hui , Zhang Jinxia , Resetkova Erika , Moulder Stacy L. , Wang Wei-Lien , Huo Lei
Published: June 2020

Background

In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant.

Methods

Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors.

Results

In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups.

Conclusions

Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.
A 95-year-old patient with unexpected coronavirus disease 2019 masked by aspiration pneumonia: a case report
Authors: Spannella Francesco , Ristori Letizia , Giulietti Federico , Re Serena , Schiavi Paola , Giordano Piero , Sarzani Riccardo
Published: June 2020

Background

Severe acute respiratory syndrome coronavirus-2 infection has become a pandemic disease (coronavirus disease 2019). The infection has moved from China to the rest of the world and Italy represents one of the most affected countries. Older adults are more susceptible to develop complications with the consequent highest mortality rates.

Case presentation

We report a case of a 95-year-old Caucasian woman affected by pneumonia, initially defined as common aspiration pneumonia in a bedridden patient with vascular dementia, which later turned out to be coronavirus disease 2019 pneumonia during the initial spread of severe acute respiratory syndrome coronavirus-2 in our district. Some features of a computed tomography scan of her chest and her clinical history with known dysphagia had led at first to a different diagnosis with a consequent exposure of health professionals to infectious risk in two distinct hospitals. In this case report, we describe the clinical/imaging features of coronavirus disease 2019 pneumonia and the diagnostic process that led to a correct diagnosis in a nonagenarian with multiple comorbidities.

Conclusions

This case report highlights both the possible pitfalls in diagnosing coronavirus disease 2019 pneumonia in very old patients with comorbidities and the greater than expected spread of the infection, even in individuals with reduced interpersonal contacts and no defined epidemiological link.
Existence–uniqueness and monotone iteration of positive solutions to nonlinear tempered fractional differential equation with p-Laplacian operator
Authors: Zhou Bibo , Zhang Lingling , Xing Gaofeng , Zhang Nan
Published: June 2020

In this paper, without requiring the complete continuity of integral operators and the existence of upper–lower solutions, by means of the sum-type mixed monotone operator fixed point theorem based on the cone $P_{h}$Ph, we investigate a kind of p-Laplacian differential equation Riemann–Stieltjes integral boundary value problem involving a tempered fractional derivative. Not only the existence and uniqueness of positive solutions are obtained, but also we can construct successively sequences for approximating the unique positive solution. As an application of our fundamental aims, we offer a realistic example to illustrate the effectiveness and practicability of the main results.
Hexagonal grid approximation of the solution of the heat equation on special polygons
Authors: Buranay Suzan C. , Arshad Nouman
Published: June 2020

We consider the first type boundary value problem of the heat equation in two space dimensions on special polygons with interior angles $\alpha _{j}\pi $αjπ, $j=1,2,\ldots,M$j=1,2,…,M, where $\alpha _{j}\in \{ \frac{1}{2},\frac{1}{3},\frac{2}{3} \} $αj∈{12,13,23}. To approximate the solution we develop two difference problems on hexagonal grids using two layers with 14 points. It is proved that the given implicit schemes in both difference problems are unconditionally stable. It is also shown that the solutions of the constructed Difference Problem 1 and Difference Problem 2 converge to the exact solution on the grids of order $O ( h^{2}+\tau ^{2} ) $O(h2+τ2) and $O ( h^{4}+\tau ) $O(h4+τ) respectively, where h and $\frac{\sqrt{3}}{2}h $32h are the step sizes in space variables $x_{1}$x1 and $x_{2}$x2 respectively and τ is the step size in time. Furthermore, theoretical results are justified by numerical examples on a rectangle, trapezoid and parallelogram.
Some results on degenerate Daehee and Bernoulli numbers and polynomials
Authors: Kim Taekyun , Kim Dae San , Kim Han Young , Kwon Jongkyum
Published: June 2020

In this paper, we study a degenerate version of the Daehee polynomials and numbers, namely the degenerate Daehee polynomials and numbers, which were actually called the degenerate Daehee polynomials and numbers of the third kind and recently introduced by Jang et al. (J. Comput. Appl. Math. 364:112343, 2020). We derive their explicit expressions and some identities involving them. Further, we introduce the multiple degenerate Daehee numbers and higher-order degenerate Daehee polynomials and numbers which can be represented in terms of integrals on the unitcube. Again, we deduce their explicit expressions and some identities related to them.
Poor infection prevention and control standards are associated with environmental contamination with carbapenemase-producing Enterobacterales and other multidrug-resistant bacteria in Swiss companion animal clinics
Authors: Schmidt Janne S. , Kuster Stefan P. , Nigg Aurélien , Dazio Valentina , Brilhante Michael , Rohrbach Helene , Bernasconi Odette J. , Büdel Thomas , Campos-Madueno Edgar I. , Gobeli Brawand Stefanie , Schuller Simone , Endimiani Andrea , Perreten Vincent , Willi Barbara
Published: June 2020

Background

Intensive medical care in companion animal clinics could pose a risk for the selection and dissemination of multidrug-resistant organisms (MDROs). Infection prevention and control (IPC) concepts are key measures to reduce the spread of MDROs, but data on IPC standards in companion animal clinics is sparse. The study assessed IPC standards in seven companion animal clinics and practices in Switzerland by structured IPC audits and combined results with environmental MDRO contamination and MDRO carriage of the personnel.

Methods

IPC audits were held between August 2018 and January 2019. The observations in 34 IPC areas were scored based on predefined criteria (not fulfilled/partially fulfilled/fulfilled = score 0/1/2). Environmental swabs and nasal and stool samples from veterinary personnel were tested for methicillin-resistant (MR) staphylococci and macrococci and for colistin-resistant, extended-spectrum β-lactamase- and carbapenemase-producing (CP)Enterobacterales(CPE). Species was identified by MALDI-TOF MS, antimicrobial resistance determined by microdilution and β-lactam resistance gene detection, and genetic relatedness assessed by REP−/ERIC-PCR and multilocus sequence typing.

Results

Of a maximum total IPC score of 68, the institutions reached a median (range) score of 33 (19–55). MDROs were detected in median (range) 8.2% (0–33.3%) of the sampling sites. Clinics with low IPC standards showed extensive environmental contamination, i.e. of intensive care units, consultation rooms and utensils. CPE were detected in two clinics; one of them showed extensive contamination with CPKlebsiella pneumoniae(ST11,blaOXA-48) and MRStaphylococcus pseudintermedius(ST551,mecA). Despite low IPC scores, environmental contamination with MDROs was low in primary opinion practices. Three employees were colonized withEscherichia coliST131 (blaCTX-M-15,blaCTX-M-27,blaCTX-M-14). Two employees carried CPE. coliclosely related to environmental (ST410,blaOXA-181) and patient-derived isolates (ST167,blaNDM-5). MRStaphylococcus aureus(ST225,mecA) and MRS. pseudintermedius(ST551,mecA) of the same sequence types and with similar resistance profiles were found in employees and the environment in two clinics.

Conclusions

The study indicates that IPC standards in companion animal clinics are variable and that insufficient IPC standards could contribute to the evolution of MDROs which can be transferred between the environment and working personnel. The implementation of IPC concepts in companion animal clinics should urgently be promoted.
Extreme anorexia nervosa: medical findings, outcomes, and inferences from a retrospective cohort
Authors: Gibson Dennis , Watters Ashlie , Cost Jeana , Mascolo Margherita , Mehler Philip S.
Published: June 2020

Background

Extreme anorexia nervosa (AN) is defined as a BMI < 15 kg/m2 in those meeting DSM-V diagnostic criteria for AN. This study seeks to define the frequency of medical complications in this group of patients in order to help inform the care of individuals < 65% ideal body weight who seek treatment for their extreme eating disorders.

Methods

Through retrospective chart review and computerized data collection, we obtained the baseline characteristics and medical findings of 281 adult patients, with AN restricting and binge-purge subtypes, admitted to the ACUTE unit for medical stabilization between May 2013 and August 2018.

Results

In this population, with a mean admitting BMI of 12.1 kg/m2 (range = 7.5–15.7), 56% admitted with bradycardia, 45% demonstrated increased liver function tests (LFTs) on admission, 64% admitted with leukopenia, 47% with anemia, and 20% presented with thrombocytopenia. During admission, 38% developed hypoglycemia, 35% developed refeeding hypophosphatemia, nearly 33% of patients developed edema, and low bone mineral density was diagnosed in almost 90% of the patients. Highly elevated LFTs (>3x upper limits of normal) predicted hypoglycemia, and low BMI predicted refeeding hypophosphatemia (p = .001).

Conclusions

Although conclusions drawn from the findings presented in this descriptive study must be tempered by relevant clinical judgement, these findings showcase that patients with extreme AN are at significantly increased risk for many serious medical complications secondary to their state of malnutrition and also with initial refeeding.
Clinical preceptor competencies for a better pharmacy education: a suggested framework for Lebanon
Authors: Zeitoun Abeer , Sacre Hala , Hallit Souheil , Zeenny Rony M. , Sili Georges , Salameh Pascale
Published: June 2020

Background

Experiential education is a core element in developing the ability of pharmacy students to apply theory to practice, solve problems, and acquire standard pharmacist competencies. To achieve this goal, preceptors play a crucial role as teachers, mentors, and evaluators. The study objective was to identify and describe the core competencies and skills considered essential to the success of clinical preceptor pharmacists in the training of future care providers, in a steadily changing environment.

Methods

A task force was formed within the Scientific Committee of the Lebanese Order of Pharmacists to map, sort, select, and adapt international competencies to the current Lebanese context.

Results

Seven roles were identified: Role model/Practitioner/Mentor, Supervisor/Facilitator/Coach/Teacher, Manager, Collaborator/Communicator, Leader, Clinical expert, and Researcher. Related competencies were also defined.

Conclusion

all aforementioned competencies are expected to improve the acquisition of learning by pharmacy trainees in Lebanon. This framework can be used by pharmacy program directors and preceptors for developmental purposes through self- or peer-evaluation processes, identifying gaps, and helping to fill the needs for a better workforce in academic and experiential pharmacy education.
Plasma-Lyte 148 and Plasma-Lyte 148 + 5% glucose compatibility with commonly used critical care drugs
Authors: Hammond Sophie , Wignell Andrew , Cooling Paul , Barrett David A. , Davies Patrick
Published: June 2020

Purpose

Plasma-Lyte is a balanced, crystalloid intravenous fluid which has been shown to avoid the hyperchloremic metabolic acidosis associated with 0.9% sodium chloride. Data on physical, pH and chemical compatibility with other medicines are essential.

Methods

The compatibility of adrenaline, dobutamine, dopamine, furosemide, midazolam, morphine and milrinone with Plasma-Lyte 148 (PLA) and Plasma-Lyte 148 with 5% glucose (PLA-G) was investigated. Control solutions were 0.9% sodium chloride and 5% glucose. Chemical stability was defined as < 5% concentration change with high-performance liquid chromatography (HPLC). Physical compatibility was assessed by checking for colour changes and precipitate formation. The pH of the admixtures was considered acceptable if between 5 and 9 at all time points. Six repeats were carried out for HPLC, 2 for physical compatibility checks and pH measurements, with all admixtures being tested at 0, 2 and 24 h after mixing.

Results

All combinations were found to be chemically stable at 0, 2 and 24 h apart from furosemide with PLA-G at 24 h and midazolam with PLA or PLA-G at both 2 and 24 h. Only midazolam was physically incompatible when mixed with both Plasma-Lyte solutions. The pH remained stable in all admixtures, although not all pH values recorded were within the range of 5–9.

Conclusion

All drugs excluding furosemide and midazolam were shown to be chemically, physically and pH stable at the tested concentrations when diluted with PLA and PLA-G.
Management of primary blast lung injury: a comparison of airway pressure release versus low tidal volume ventilation
Authors: Scott Timothy E. , Das Anup , Haque Mainul , Bates Declan G. , Hardman Jonathan G.
Published: June 2020

Background

Primary blast lung injury (PBLI) presents as a syndrome of respiratory distress and haemoptysis resulting from explosive shock wave exposure and is a frequent cause of mortality and morbidity in both military conflicts and terrorist attacks. The optimal mode of mechanical ventilation for managing PBLI is not currently known, and clinical trials in humans are impossible due to the sporadic and violent nature of the disease.

Methods

A high-fidelity multi-organ computational simulator of PBLI pathophysiology was configured to replicate data from 14 PBLI casualties from the conflict in Afghanistan. Adaptive and responsive ventilatory protocols implementing low tidal volume (LTV) ventilation and airway pressure release ventilation (APRV) were applied to each simulated patient for 24 h, allowing direct quantitative comparison of their effects on gas exchange, ventilatory parameters, haemodynamics, extravascular lung water and indices of ventilator-induced lung injury.

Results

The simulated patients responded well to both ventilation strategies. Post 24-h investigation period, the APRV arm had similar PF ratios (137 mmHg vs 157 mmHg), lower sub-injury threshold levels of mechanical power (11.9 J/min vs 20.7 J/min) and lower levels of extravascular lung water (501 ml vs 600 ml) compared to conventional LTV. Driving pressure was higher in the APRV group (11.9 cmH2O vs 8.6 cmH2O), but still significantly less than levels associated with increased mortality.

Conclusions

Appropriate use of APRV may offer casualties with PBLI important mortality-related benefits and should be considered for management of this challenging patient group.
A patient with cystic duct remnant calculus treated by laparoscopic surgery combined with near-infrared fluorescence cholangiography
Authors: Matsudaira Shinichi , Fukumoto Tsuyoshi , Yarita Akinaga , Hamada Joji , Hisada Masayuki , Fukushima Junichi , Kawarabayashi Nobuaki
Published: June 2020

Background

The recurrence of symptoms present before cholecystectomy may be caused by a cystic duct remnant. The resolution of cystic duct remnant syndrome may require surgical resection, but identification of the duct remnant during laparoscopic surgery may be difficult because of adhesions following the previous procedure. Open surgery, which is more invasive than laparoscopic surgery, is frequently chosen to avoid bile duct injury.

Case presentation

The patient was a 24-year-old woman with previous laparoscopic cholecystectomy for chronic cholecystitis and repeated attacks of biliary colic. The postoperative course was uneventful, but computed tomography revealed a remnant cystic duct calculus. Ten months after surgery, the patient returned to our department for right hypochondriac pain. Laparoscopic remnant cystic duct resection was performed with intraoperative near-infrared (NIR) fluorescence cholangiography to visualize the common bile duct and remnant cystic duct. The postoperative course was uneventful and the patient was discharged on day 3 after surgery. At the 6-month follow-up, she had no recurrence of pain.

Conclusion

Laparoscopic surgery with NIR cholangiography is a safe and effective alternative for the removal of a cystic duct remnant calculus after cholecystectomy.
A cluster randomized controlled trial to assess the efficacy of a telehealth-based train-the-trainer mealtime intervention delivered by respite care center volunteers to caregivers of persons with dementia to improve nutritional outcomes and quality of life
Authors: Amella Krug Elaine J. , Qanungo Suparna , Martin Kelley L. , Mueller Martina , Madisetti Mohan , Kelechi Teresa J.
Published: June 2020

Background

Persons with dementia with mild to moderate cognitive impairment are at risk for developing impairments with activities of daily living such as the ability to feed oneself, that negatively influence health. Lack of caregiver skills related to mealtime planning for persons with dementia and the ability to cope with dysfunctional behaviors are well-documented factors that influence nutritional status outcomes, lead to weight loss, poor quality of life, and impact their ability to remain at home.

Methods

A cluster randomized controlled trial with a parallel mixed methods evaluation processes will be conducted to examine the efficacy of a train-the-trainer program using non-paid volunteers in respite care centers to deliver a telehealth mealtime intervention guided by the theory-basedC3P Model—Change the Person, Change the People, Change the Place (C3P).In this six-month study, dyads of caregivers and persons with mild to moderate dementia receiving respite care services will be randomized to receive either the telehealth intervention or enhanced usual care. Within the intervention group, dyads will be partnered with a C3P trained volunteer who will work with caregivers via videoconference to devise and implement mealtime plans. Under usual care, dyads will receive standardized educational materials modified fromThe Savvy Caregiver Programfor Alzheimer’s disease. The primary outcomes include weight maintenance or gain of the person with dementia and quality of life of the caregiver. A multi-level evaluation process utilizing respite center administrators and directors, volunteers, and caregivers will explore intervention fidelity, acceptability and sustainability. Using both the CONSORT and SPIRIT checklists as guidance, the comprehensive study design is more fully described in this manuscript.

Discussion

In this trial, we will lay the groundwork to examine the efficacy and sustainability of a train-the-trainer telehealth program that could be widely disseminated by national Alzheimer’s organizations and readily adopted by community agencies to provide additional resources to assist families in managing mealtimes at home, while promoting the quality of life of both the caregiver and the person with dementia.

Trial registration

This study was registered with clinicaltrials.gov:NCT03622814on August 9, 2018..