bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the UK Public Health Skills and Knowledge Framework (PHSKF): implications for international competency frameworks
Authors: Bornioli Anna , Evans David , Cotter Claire
Published: June 2020

Background

The value of competency frameworks for developing the public health workforce is widely acknowledged internationally. However, there is a lack of formal evaluations of such frameworks. In the UK, the Public Health Skills and Knowledge Framework (PHSKF) is a key tool for the public health workforce across the UK, and this study presents the evaluation of the PHSKF 2016 version, with the aim of reflecting on implications for international public health competency frameworks.

Methods

A sequential explanatory design was employed. An online survey (n = 298) was completed with stakeholders across the four UK nations and different sectors. This was followed by 18 telephone interviews with stakeholders and survey completers. Quantitative results were analysed descriptively; qualitative transcripts were analysed with thematic analysis.

Results

Most respondents had used the PHSKF occasionally or rarely, and most users found it useful (87%) and easy to use (82%). Main purposes of use included team/workforce development (e.g. setting of standards) and professional development (e.g. identify professional development opportunities). Some positive experiences emerged of uses of the PHSKF to support organisational redevelopments. However, 23% of respondents had never used the framework. Areas for improvement included greater clarity on purpose and audience, the need for more support from employers and for clear career progression opportunities, and stronger links with other competency frameworks.

Conclusions

The development of a digital version of the PHSKF, together with improving buy-in from the workforce and employers could make an important contribution towards UK public health workforce development. Further evaluation and shared learning internationally of the implementation of public health competency frameworks would support global public health workforce development.
Female sex workers perspectives and concerns regarding HIV self-testing: an exploratory study in Tanzania
Authors: Nnko Soori , Nyato Daniel , Kuringe Evodius , Casalini Caterina , Shao Amani , Komba Albert , Changalucha John , Wambura Mwita
Published: June 2020

Background

HIV testing is a gateway to HIV care and treatment for people diagnosed with HIV and can link those with negative results to HIV preventive services. Despite the importance of HIV testing services (HTS) in HIV control, uptake of HTS among female sex workers (FSWs) across sub-Saharan Africa (SSA) remains sub-optimal. Concerns about stigma associated with sex work and fear of loss of livelihood if HIV status becomes known, are some of the restrictions for FSWs to utilize HTS offered through health care facilities. Introduction of HIV self-testing (HIVST) may mitigate some of the barriers for the uptake of HTS. This study explored the acceptability of FSWs towards the introduction of HIVST in Tanzania.

Methods

We conducted an exploratory study employing in-depth interviews (IDI) and participatory group discussions (PGD) with FSWs in selected regions of Tanzania. Study participants were recruited through snowball sampling. Data were thematically analysed by two analysts using NVivo software. The analysis was informed by the social-ecological model and focused on factors associated with the acceptability of HIVST.

Results

We conducted 21 PGD sessions involving 227 FSWs. Twenty three IDIs were conducted to complement data collected through PGD. Our study has demonstrated that FSWs are enthusiastic toward HIVST. Convenience (time and cost saved), and belief that HIVST will increase privacy and confidentiality motivated participants’ support for the self-testing approach. Participants did express concerns about their ability to interpret and trust the results of the test. Participants also expressed concern that HIVST could cause personal harm, including severe distress and self-harm for individuals with a reactive test. Very likely, concern about adverse effects of HIVST was linked to the study participants’ lay perception that HIVST would be provided only through unassisted modality.

Conclusions

FSWs demonstrated high enthusiasm to use the HIVST once it becomes available. Expectations for increased confidentiality, autonomy, and reduced opportunity costs were among the leading factors that attracted FSWs to HIVST. The major obstacles to the acceptability of HIVST included fear of HIV reactive test and not trusting self-diagnoses. Our findings underscore the importance of providing adequate access to counselling and referral services in conjunction with HIVST.
Thoracic perfusion of recombinant mutant human tumor necrosis factor (rmhTNF) can be considered as a good adjunct in the treatment of malignant pleural effusion caused by lung cancer
Authors: Fu Tian , Lin Yong , Zeng Qingdi , Yao Wei , Han Liping
Published: June 2020

Background

Tumor necrosis factor (TNF) has been investigated to be correlated with the occurrence and progression of lung cancer. This investigation was to assess the efficacy and safety of recombinant mutant human tumor necrosis factor (rmhTNF) for controlling malignant pleural effusion (MPE) through thoracic perfusion.

Methods

Through searching from MEDLINE, Web of Science, EMBASE, Cochrance Library, OVID and China National Knowledge Infrastructure (CNKI), a total of 12 studies with 694 patients were included in this study. A series of meta-analysis methods were used to analyze the extracted data.

Results

Thoracic perfusion of rmhTNF combined with cisplatin promoted the objective response rate (ORR) (P < 0.001; odds ratio = 4.49) and the quality of life (QOL) of patients with MPE (P < 0.001; odds ratio = 10.33), as compared with cisplatin alone. Although the participation of rmhTNF increased the incidence of fever (P < 0.001), it seemed to relieve the adverse reactions in the digestive tract (P = 0.017).

Conclusions

Thoracic perfusion of rmhTNF contributes to the treatment of MPE and improves the QOL of MPE patients.
Exploring characteristics of COPD patients with clinical improvement after integrated disease management or usual care: post-hoc analysis of the RECODE study
Authors: Meijer Eline , van Eeden Annelies E. , Kruis Annemarije L. , Boland Melinde R. S. , Assendelft Willem J. J. , Tsiachristas Apostolos , Rutten-van Mölken Maureen P. M. H. , Kasteleyn Marise J. , Chavannes Niels H.
Published: June 2020

Background

The cluster randomized controlled trial on (cost-)effectiveness of integrated chronic obstructive pulmonary disease (COPD) management in primary care (RECODE) showed that integrated disease management (IDM) in primary care had no effect on quality of life (QOL) in COPD patients compared with usual care (guideline-supported non-programmatic care). It is possible that only a subset of COPD patients in primary care benefit from IDM. We therefore examined which patients benefit from IDM, and whether patient characteristics predict clinical improvement over time.

Method

Post-hoc analyses of the RECODE trial among 1086 COPD patients. Logistic regression analyses were performed with baseline characteristics as predictors to examine determinants of improvement in QOL, defined as a minimal decline in Clinical COPD Questionnaire (CCQ) of 0.4 points after 12 and 24 months of IDM. We also performed moderation analyses to examine whether predictors of clinical improvement differed between IDM and usual care.

Results

Regardless of treatment type, more severe dyspnea (MRC) was the most important predictor of clinically improved QOL at 12 and 24 months, suggesting that these patients have most room for improvement. Clinical improvement with IDM was associated with female gender (12-months) and being younger (24-months), and improvement with usual care was associated with having a depression (24-months).

Conclusions

More severe dyspnea is a key predictor of improved QOL in COPD patients over time. More research is needed to replicate patient characteristics associated with clinical improvement with IDM, such that IDM programs can be offered to patients that benefit the most, and can potentially be adjusted to meet the needs of other patient groups as well.

Trial registration

Netherlands Trial Register, NTR2268. Registered 31 March 2010.
A predictive analytics model for differentiating between transient ischemic attacks (TIA) and its mimics
Authors: Stanciu Alia , Banciu Mihai , Sadighi Alireza , Marshall Kyle A. , Holland Neil R. , Abedi Vida , Zand Ramin
Published: June 2020

Background

Transient ischemic attack (TIA) is a brief episode of neurological dysfunction resulting from cerebral ischemia not associated with permanent cerebral infarction. TIA is associated with high diagnostic errors because of the subjective nature of findings and the lack of clinical and imaging biomarkers. The goal of this study was to design and evaluate a novel multinomial classification model, based on a combination of feature selection mechanisms coupled with logistic regression, to predict the likelihood of TIA, TIA mimics, and minor stroke.

Methods

We conducted our modeling on consecutive patients who were evaluated in our health system with an initial diagnosis of TIA in a 9-month period. We established the final diagnoses after the clinical evaluation by independent verification from two stroke neurologists. We used Recursive Feature Elimination (RFE) and Least Absolute Shrinkage and Selection Operator (LASSO) for prediction modeling.

Results

The RFE-based classifier correctly predicts 78% of the overall observations. In particular, the classifier correctly identifies 68% of the cases labeled as “TIA mimic” and 83% of the “TIA” discharge diagnosis. The LASSO classifier had an overall accuracy of 74%. Both the RFE and LASSO-based classifiers tied or outperformed the ABCD2 score and the Diagnosis of TIA (DOT) score. With respect to predicting TIA, the RFE-based classifier has 61.1% accuracy, the LASSO-based classifier has 79.5% accuracy, whereas the DOT score applied to the dataset yields an accuracy of 63.1%.

Conclusion

The results of this pilot study indicate that a multinomial classification model, based on a combination of feature selection mechanisms coupled with logistic regression, can be used to effectively differentiate between TIA, TIA mimics, and minor stroke.
E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation
Authors: Wang Qixin , Sundar Isaac K. , Li Dongmei , Lucas Joseph H. , Muthumalage Thivanka , McDonough Samantha R. , Rahman Irfan
Published: June 2020

Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.
Do acute changes in ambient air pollution increase the risk of potentially fatal cardiac arrhythmias in patients with implantable cardioverter defibrillators?
Authors: Dales Robert , Lee Douglas S. , Wang Xuesong , Cakmak Sabit , Szyszkowicz Mieczyslaw , Shutt Robin , Birnie David
Published: June 2020

Background

Daily changes in ambient air pollution have been associated with cardiac morbidity and mortality. Precipitating a cardiac arrhythmia in susceptible individuals may be one mechanism. We investigated the influence of daily changes in air pollution in the Province of Ontario, Canada on the frequency of discharges from implantable cardio defibrillators (ICDs) which occur in response to potentially life threatening arrhythmias.

Methods

Using a case- crossover design, we compared ambient air pollution concentrations on the day of an ICD discharge to other days in the same month and year in 1952 patients. We adjusted for weather, lagged the exposure data from 0 to 3 days, and stratified the results by several patient-related characteristics.

Results

Median (interquartile range) for ozone (O3), fine particulate matter (PM2.5), sulphur dioxide (SO2) and nitrogen dioxide (NO2) were 26.0 ppb (19.4, 33.0), 6.6 μg/m3 (4.3, 10.6), 1.00 ppb (0.4,2.1), 10.0 ppb (6.0,15.3) respectively. Unlagged odds ratios (95%) for an ICD discharge associated with an interquartile range increase in pollutant were 0.97 (0.86, 1.09) for O3, 0.99 (0.92, 1.06) for PM2.5, 0.97 (0.91, 1.03) for SO2, and 1.00 (0.89, 1.12) for NO2.

Conclusion

We found no evidence that the concentrations of ambient air pollution observed in our study were a risk factor for potentially fatal cardiac arrhythmias in patients with ICDs.
The relationship between total cholesterol and postpartum impaired glucose tolerance in women with gestational diabetes mellitus
Authors: Wang Dongyu , Ding Wenjing , Xu Shuqia , Chen Haitian , Liu Bin , Wang Zilian
Published: June 2020

Background

History of gestational diabetes mellitus (GDM) and serum lipid abnormalities were associated with postpartum impaired glucose tolerance. To investigate the association between concentration of total cholesterol (TC), at the time of GDM diagnosis, and risk of postpartum glucose intolerance.

Methods

Women who were diagnosed GDM with a live singleton delivery between January 1, 2013 and December 31, 2017 were included. Women were grouped based on the TC quartiles at the time of GDM diagnosis and had an OGTT at 6–12 weeks after delivery. The relationship between TC and the risk of postpartum glucose intolerance was assessed by COX regression.

Results

A total of 845 women were in the final analysis. Higher TC quartile at diagnosis of GDM was associated with a decreased risk of postpartum glucose intolerance. Women in the highest TC quartile (>7.0 mmol L− 1) had approximately only half-risk of any postpartum glucose intolerance, compared with women in the lowest TC quartile (<5.5 mmol L− 1).

Conclusions

The decreased concentration of TC, at the time of GDM diagnosis, was related to an increased risk of postpartum abnormal glucose regulation in GDM women. Therefore, because both excessively increased and decreased TC were associated with pregnancy and postpartum complications, the optimal concentration of maternal TC throughout pregnancy remained to be further researched.
LDL-cholesterol to HDL-cholesterol ratio discordance with lipid parameters and carotid intima-media thickness: a cohort study in China
Authors: Lou Yanmei , Li Xue , Cao Liming , Qin Pei , Shi Jing , Zhang Yanyan , Wang Changyi , Ma Jianping , Wang Li , Peng Xiaolin , Chen Hongen , Xu Shan , Hu Fulan , Zhao Yashuang , Zhao Ping
Published: June 2020

Background

The discordance of the low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with alterative lipid parameters may explain the inconsistent association of CIMT with the LDL-C/HDL-C ratio. Therefore, this study aimed to explore the associations between LDL-C/HDL-C ratio discordance with alternative lipid parameters and elevated carotid intima-media thickness (CIMT) risk in a large cohort in Beijing, China.

Methods

In total, 13,612 adults who didn’t have elevated CIMT at baseline and who participated in at least one follow-up of annual examination between 2009 and 2016 were included in this cohort study. A multivariable Cox regression model was utilized to evaluate the associations of discordance of the LDL-C/HDL-C ratio with TC, TGs, LDL-C and HDL-C with elevated CIMT risk.

Results

During 37,999 person-years of follow-up, 2004 individuals (1274 men and 730 women) developed elevated CIMT. Among individuals with normal TC and TGs, 16.6 and 15.2% individuals had a discordantly high LDL-C/HDL-C ratio, respectively, and the risk of elevated CIMT increased by 1.54 (95% CI 1.33, 1.77) and 1.53 (95% CI 1.33, 1.76), respectively, comparing to individuals with a concordantly low LDL-C/HDL-C ratio. A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with LDL-C and HDL-C (P < 0.001). A low LDL-C/HDL-C ratio with discordantly normal HDL-C and high LDL-C (13.2% of individuals) had a 32% (HR = 1.32, 95% CI 1.11, 1.57) higher risk of elevated CIMT than concordantly low LDL-C and normal HDL-C. Sensitivity analysis by excluding CIMT developed in the first 2 years follow-up further confirmed the above results.

Conclusions

A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with TC, TGs, LDL-C and HDL-C Even a low LDL-C/HDL-C ratio with discordantly high LDL-C and normal HDL-C could also significantly increase CIMT risk. Individuals should maintain both the LDL-C/HDL-C ratio and LDL-C at normal levels to prevent elevated CIMT.
The four of structural genes sequences of a porcine epidemic diarrhea virus from domestic piglet in Fujian, China
Authors: Dong Bo , Dai Ailing , Li Xiaohua , Yang Xiaoyan
Published: June 2020

A prevalent PEDV strain, designated FJLY06, was isolated from Fujian, China. The four of structural genes sequences of PEDV obtained were analyzed to determine their phylogenetic relationships and homology respectively, revealing that FJLY06 was highly homologous to virulent PEDV strains. The four structural genes all differed genetically from the vaccine strain CV777. The sequence alignment results further showed that N, M and E genes of Chinese PEDV strains is highly conserved. Compared with the vaccine strain CV777, 8 mutations were detected in COE of FJLY06 S gene. The recombination analysis revealed FJLY06 is similar to other pandemic strains in China with a variant S gene, and maybe a reason for recent vaccination failures.
KLF4 defines the efficacy of the epidermal growth factor receptor inhibitor, erlotinib, in triple-negative breast cancer cells by repressing the EGFR gene
Authors: Roberts Melyssa S. , Anstine Lindsey J. , Finke Viviane S. , Bryson Benjamin L. , Webb Bryan M. , Weber-Bonk Kristen L. , Seachrist Darcie D. , Majmudar Parth R. , Keri Ruth A.
Published: June 2020

Background

Triple-negative breast cancer (TNBC) is characterized by high rates of recurrence and poor overall survival. This is due, in part, to a deficiency of targeted therapies, making it essential to identify therapeutically targetable driver pathways of this disease. While epidermal growth factor receptor (EGFR) is expressed in 60% of TNBCs and drives disease progression, attempts to inhibit EGFR in unselected TNBC patients have had a marginal impact on outcomes. Hence, we sought to identify the mechanisms that dictate EGFR expression and inhibitor response to provide a path for improving the utility of these drugs. In this regard, the majority of TNBCs express low levels of the transcription factor, Krüppel-like factor 4 (KLF4), while a small subset is associated with high expression. KLF4 and EGFR have also been reported to have opposing actions in TNBC. Thus, we tested whether KLF4 controls the expression of EGFR and cellular response to its pharmacological inhibition.

Methods

KLF4 was transiently overexpressed in MDA-MB-231 and MDA-MB-468 cells or silenced in MCF10A cells. Migration and invasion were assessed using modified Boyden chamber assays, and proliferation was measured by EdU incorporation. Candidate downstream targets of KLF4, including EGFR, were identified using reverse phase protein arrays of MDA-MB-231 cells following enforced KLF4 expression. The ability of KLF4 to suppress EGFR gene and protein expression and downstream signaling was assessed by RT-PCR and western blot, respectively. ChIP-PCR confirmed KLF4 binding to the EGFR promoter. Response to erlotinib in the context of KLF4 overexpression or silencing was assessed using cell number and dose-response curves.

Results

We report that KLF4 is a major determinant of EGFR expression and activity in TNBC cells. KLF4 represses transcription of the EGFR gene, leading to reduced levels of total EGFR, its activated/phosphorylated form (pEGFR), and its downstream signaling intermediates. Moreover, KLF4 suppression of EGFR is a necessary intermediary step for KLF4 to inhibit aggressive TNBC phenotypes. Most importantly, KLF4 dictates the sensitivity of TNBC cells to erlotinib, an FDA-approved inhibitor of EGFR.

Conclusions

KLF4 is a major regulator of the efficacy of EGFR inhibitors in TNBC cells that may underlie the variable effectiveness of such drugs in patients.
instaGRAAL: chromosome-level quality scaffolding of genomes using a proximity ligation-based scaffolder
Authors: Baudry Lyam , Guiglielmoni Nadège , Marie-Nelly Hervé , Cormier Alexandre , Marbouty Martial , Avia Komlan , Mie Yann Loe , Godfroy Olivier , Sterck Lieven , Cock J. Mark , Zimmer Christophe , Coelho Susana M. , Koszul Romain
Published: June 2020

Hi-C exploits contact frequencies between pairs of loci to bridge and order contigs during genome assembly, resulting in chromosome-level assemblies. Because few robust programs are available for this type of data, we developed instaGRAAL, a complete overhaul of the GRAAL program, which has adapted the latter to allow efficient assembly of large genomes. instaGRAAL features a number of improvements over GRAAL, including a modular correction approach that optionally integrates independent data. We validate the program using data for two brown algae, and human, to generate near-complete assemblies with minimal human intervention.
Methotrexate-loaded multifunctional nanoparticles with near-infrared irradiation for the treatment of rheumatoid arthritis
Authors: Ha You-Jung , Lee Sun-Mi , Mun Chin Hee , Kim Hyung Joon , Bae Yonghee , Lim Ji-Hee , Park Kyu-Hyung , Lee Soo-Kon , Yoo Kyung-Hwa , Park Yong-Beom
Published: June 2020

Backgrounds

Despite the advances of rheumatoid arthritis (RA) therapeutics, several patients do not receive adequate treatment due to the toxicity and/or insufficient response of drugs. The aim of this study is to design photothermally controlled drug release from multifunctional nanoparticles (MNPs) at a near-infrared (NIR) irradiated site to improve therapeutic efficacy for RA and reduce side effects.

Methods

Au film was deposited onto methotrexate (MTX)-loaded poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles, resulting in MTX-loaded MNPs. The synergistic effects of MTX-loaded MNPs with NIR irradiation were investigated using RA fibroblast-like synoviocytes (FLSs) and collagen-induced arthritis (CIA) mice.

Results

Upon NIR irradiation, NIR resonance of the Au half-shell generated heat locally, accelerating MTX release from PLGA nanoparticles. In vivo NIR images of MTX-loaded MNPs indicated effective delivery of the MNPs to the inflamed joints. Moreover, in collagen-induced arthritis mice, MTX-loaded MNPs containing 1/1400 of MTX solution (repeated-dose administration) had therapeutic effects comparable to conventional treatment with MTX solution. In vitro experiments showed higher therapeutic efficacy of MTX-loaded MNPs with NIR irradiation than that of chemotherapy alone.

Conclusions

A combination therapy of MTX-loaded MNP and NIR irradiation showed durable and good treatment efficacy for the suppression of arthritis in a single administration of small dose of MTX. Our results demonstrate that the treatment modality using drug-loaded MNP with NIR irradiation may be a promising therapeutic strategy for the treatment of RA and allow in vivo NIR optical imaging.
Proteomic analysis in lupus mice identifies Coronin-1A as a potential biomarker for lupus nephritis
Authors: Nicolaou Orthodoxia , Sokratous Kleitos , Makowska Zuzanna , Morell María , De Groof Aurélie , Montigny Pauline , Hadjisavvas Andreas , Michailidou Kyriaki , Oulas Anastasis , Spyrou George M. , Demetriou Christiana , Alarcón-Riquelme Marta E. , Psarellis Savvas , Kousios Andreas , Lauwerys Bernard , Kyriacou Kyriacos
Published: June 2020

Background

Approximately 50% of systemic lupus erythematosus (SLE) patients develop nephritis, which is among the most severe and frequent complications of the disease and a leading cause of morbidity and mortality. Despite intensive research, there are still no reliable lupus nephritis (LN) markers in clinical use that can assess renal damage and activity with a high sensitivity and specificity. To this end, the aim of this study was to identify new clinically relevant tissue-specific protein biomarkers and possible underlying molecular mechanisms associated with renal involvement in SLE, using mass spectrometry (MS)-based proteomics.

Methods

Kidneys were harvested from female triple congenic B6.NZMsle1/sle2/sle3 lupus mice model, and the respective sex- and age-matched C57BL/6 control mice at 12, 24 and 36 weeks of age, representing pre-symptomatic, established and end-stage LN, respectively. Proteins were extracted from kidneys, purified, reduced, alkylated and digested by trypsin. Purified peptides were separated by liquid chromatography and analysed by high-resolution MS. Data were processed by the Progenesis QIp software, and functional annotation analysis was performed using DAVID bioinformatics resources. Immunofluorescence and multiple reaction monitoring (MRM) MS methods were used to confirm prospective biomarkers in SLE mouse strains as well as human serum samples.

Results

Proteomic profiling of kidney tissues from SLE and control mice resulted in the identification of more than 3800 unique proteins. Pathway analysis revealed a number of dysregulated molecular pathways that may be mechanistically involved in renal pathology, including phagosome and proximal tubule bicarbonate reclamation pathways. Proteomic analysis supported by human transcriptomic data and pathway analysis revealed Coronin-1A, Ubiquitin-like protein ISG15, and Rho GDP-dissociation inhibitor 2, as potential LN biomarkers. These results were further validated in other SLE mouse strains using MRM-MS. Most importantly, experiments in humans showed that measurement of Coronin-1A in human sera using MRM-MS can segregate LN patients from SLE patients without nephritis with a high sensitivity (100%) and specificity (100%).

Conclusions

These preliminary findings suggest that serum Coronin-1A may serve as a promising non-invasive biomarker for LN and, upon validation in larger cohorts, may be employed in the future as a screening test for renal disease in SLE patients.
Sacrococcygeal teratoma with preterm delivery: a case report
Authors: Baró Anna Moreno , Perez Silvia Pina , Costa Montserrat Mestre , Heredia Cristina Lesmes , Azuara Laura Serra , Juanos Judith Lleberia , Lapiedra Marc Zamora
Published: June 2020

Background

Sacrococcygeal teratoma is one of the most frequently prenatally diagnosed neoplasias. Obstetric ultrasound has a role in the diagnosis and management of these tumors during pregnancy. In this report, we describe a multidisciplinary approach in a case of a patient with sacrococcygeal teratomas and preterm delivery, as well as postnatal outcomes.

Case presentation

A 26-year-old Caucasian woman at 20.3 weeks of gestation with a normal gestational course and no relevant medical or surgical history was referred to our institution with a sacrococcygeal mass diagnosis. Magnetic resonance imaging confirmed the diagnosis of sacrococcygeal teratoma type I according to the Altman classification. Follow-up with ultrasound showed an increase in the size of the mass up to 190 × 150 mm, high Doppler flow, and severe polyhydramnios. At 35.1 weeks of gestation, the patient had premature rupture of membranes, and an emergency cesarean section was performed due to recurrent late decelerations detected by fetal heart rate monitoring. Afterward, surgery was performed successfully at 36 hours of life. Posterior controls revealed normal and healthy child growth.

Conclusions

This case report demonstrates the importance of a multidisciplinary approach to offer the best neonatal outcomes by performing early surgery, as well as the need for follow-up by ultrasound in order to minimize complications by assessing mass growth, Doppler flow, and amniotic fluid.
Novel venom-based peptides (P13 and its derivative—M6) to maintain self-renewal of human embryonic stem cells by activating FGF and TGFβ signaling pathways
Authors: Ma Rui , Ren Zhili , Li Bin , Siu Shirley W. I. , Chen Guokai , Kwok Hang Fai
Published: June 2020

Background

In our previous study, a venom-based peptide named Gonearrestide (also named P13) was identified and demonstrated with an effective inhibition in the proliferation of colon cancer cells. In this study, we explored if P13 and its potent mutant M6 could promote the proliferation of human embryonic stem cells and even maintain their self-renewal.

Methods

The structure-function relationship analysis on P13 and its potent mutant M6 were explored from the molecular mechanism of corresponding receptor activation by a series of inhibitor assay plus molecular and dynamics simulation studies.

Results

An interesting phenomenon is that P13 (and its potent mutant M6), an 18AA short peptide, can activate both FGF and TGFβ signaling pathways. We demonstrated that the underlying molecular mechanisms of P13 and M6 could cooperate with proteoglycans to complete the “dimerization” of FGFR and TGFβ receptors.

Conclusions

Taken together, this study is the first research finding on a venom-based peptide that works on the FGF and TGF-β signaling pathways to maintain the self-renewal of hESCs.
Hermite–Hadamard inequality for fractional integrals of Caputo–Fabrizio type and related inequalities
Authors: Gürbüz Mustafa , Akdemir Ahmet Ocak , Rashid Saima , Set Erhan
Published: June 2020

In this article, firstly, Hermite–Hadamard’s inequality is generalized via a fractional integral operator associated with the Caputo–Fabrizio fractional derivative. Then a new kernel is obtained and a new theorem valid for convex functions is proved for fractional order integrals. Also, some applications of our main findings are given.
Existence of least energy nodal solution for Kirchhoff–Schrödinger–Poisson system with potential vanishing
Authors: Zhang Jin-Long , Wang Da-Bin
Published: June 2020

This paper deals with the following Kirchhoff–Schrödinger–Poisson system: $$ \textstyle\begin{cases} -(a+b\int _{\mathbb{R}^{3}} \vert \nabla u \vert ^{2}\,dx)\Delta u+V(x)u+\phi u=K(x)f(u)&\text{in } \mathbb{R}^{3}, \\ -\Delta \phi =u^{2}&\text{in } \mathbb{R}^{3}, \end{cases} $$

{

−
(
a
+
b

∫

R
3

|
∇
u

|
2

d
x
)
Δ
u
+
V
(
x
)
u
+
ϕ
u
=
K
(
x
)
f
(
u
)

in 

R
3

,

−
Δ
ϕ
=

u
2

in 

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3

,

where a, b are positive constants, $K(x)$
K
(
x
)
, $V(x)$
V
(
x
)
are positive continuous functions vanishing at infinity, and $f(u)$
f
(
u
)
is a continuous function. Using the Nehari manifold and variational methods, we prove that this problem has a least energy nodal solution. Furthermore, if f is an odd function, then we obtain that the equation has infinitely many nontrivial solutions.
Existence of nontrivial solutions for fractional Schrödinger equations with electromagnetic fields and critical or supercritical nonlinearity
Authors: Li Quanqing , Teng Kaimin , Wang Wenbo , Zhang Jian
Published: June 2020

In this paper, we study the following fractional Schrödinger equation with electromagnetic fields and critical or supercritical nonlinearity: $$ (-\Delta )_{A}^{s}u+V(x)u=f\bigl(x, \vert u \vert ^{2}\bigr)u+\lambda \vert u \vert ^{p-2}u,\quad x \in \mathbb{R}^{N}, $$(−Δ)Asu+V(x)u=f(x,|u|2)u+λ|u|p−2u,x∈RN, where $(-\Delta )_{A}^{s}$(−Δ)As is the fractional magnetic operator with $0< s<1$0<s<1, $N>2s$N>2s, $\lambda >0$λ>0, $2_{s}^{*}=\frac{2N}{N-2s}$2s∗=2NN−2s, $p\geq 2_{s}^{*}$p≥2s∗, f is a subcritical nonlinearity, and $V \in C(\mathbb{R}^{N},\mathbb{R})$V∈C(RN,R) and $A \in C(\mathbb{R}^{N}, \mathbb{R}^{N})$A∈C(RN,RN) are the electric and magnetic potentials, respectively. Under some suitable conditions, by variational methods we prove that the equation has a nontrivial solution for small $\lambda >0$λ>0. Our main contribution is related to the fact that we are able to deal with the case $p>2_{s}^{*}$p>2s∗.
Dipeptidyl Peptidase-4 inhibitors use in type II diabetic patients in a tertiary hospital
Authors: Mak Woh Yon , Nagarajah Jivanraj R. , Abdul Halim Hannah , Ramadas Anitha , Mohd Pauzi Zulsairi , Pee Lay Ting , Jagan Nirmala
Published: June 2020

Background

In Malaysia, for more than a decade, dipeptidyl peptidase-4 inhibitors (DPP-4i) are among the oral antidiabetic medications used as monotherapy or in combination to manage type II diabetes mellitus (T2DM). These medications are known for the efficacy in glycated haemoglobin (HbA1c) reduction and weight neutral effect with minimal hypoglycaemia occurrence. This study aimed to identify the outcomes of DPP-4i use in one of the largest tertiary public hospital in Southeast Asia.

Methods

This is a retrospective cross sectional study conducted in 2016, where stratified sampling method was used. Patients with T2DM treated with available DPP-4i; namely Linagliptin, Saxagliptin, Sitagliptin and Vildagliptin, for at least 3 months were identified from the pharmacy record. Medical records from Physician Clinic in Hospital Kuala Lumpur (HKL) were reviewed. Data on demographic, anthropometric, antidiabetic treatment modalities, laboratory and documented outcomes were collected. Outcomes endpoints which include changes in HbA1c, fasting blood glucose (FBG), and body weight were recorded and analysed. Adverse drug reactions (ADR) documented were also reported.

Results and discussion

A total of one hundred and five patients were recruited. The patients were 49.5% men (n = 52), with a mean age of 57 years, mean HbA1c of 8.5% (69 mmol/mol) and mean BMI of 29.5 kg/m2. At least 50% of the patients had T2DM for more than 10 years and more than two third of these patients had both T2DM and hypertension. Thirty nine patients were on Vildagliptin, 32 on Sitagliptin, 26 on Saxagliptin and the remaining on Linagliptin. The most commonly prescribed DPP-4i were Vildagliptin and Sitagliptin. Majority of the patients (90.4%) were prescribed with Metformin, with 62.8% of patients on fixed-dose combination, and the remaining on add-on Metformin therapy. Use of DPP-4i as an adjunct was associated with a mean reduction of 0.9% (9 mmol/mol) in HbA1c (p < 0.0001) and 1.15 mmol/L (19.82 mg/dL) in FBG (p = 0.001) without significant weight changes (p = 0.745). Sitagliptin had the highest reduction in HbA1c (1.66%,19 mmol/mol; p-value< 0.0001). Twelve ADRs were reported with the highest report on gastrointestinal intolerance (n = 7). None of the ADR reported caused any significant harm to the patients.

Conclusion

Overall, use of these DPP-4i as an adjunct antidiabetic was associated with reduction in HbA1c.
Why workers’ turnover is so high: managed flexibility and the intermediary chain of China’s migrant labor market
Authors: Liu Zixi , Zhu Jianghuafeng
Published: June 2020

Looking at how the global factories organize and control their labor forces sustainably and effectively, a considerable number of studies have focused on the politics of production but have seldom discussed the organization of the labor market beyond the workplace. Based on fieldwork about labor recruitment in the manufacturing industry in City W, this article analyzes the organizational ecology of the current labor market and its embedded institutional environment. It shows that to satisfy factories’ demand for flexible labor, the organizational ecology of the labor market has developed an intermediary chain characterized by multilevel outsourcing, an elaborate division of labor, and constant internal competition and cooperation. Although the intermediary chain coordinates flexible production, its profit-making model and business strategies drive up labor costs, consistently aggravating labor turnover and constructing low-skilled labor force. Local government, enterprises, and workers are the three forces constituting the institutional environment that nurtures this intermediary chain. Each of them makes use of “flexibility” for their own interests, unintentionally increasing the risks to the production system.
Current understanding of adult neurogenesis in the mammalian brain: how does adult neurogenesis decrease with age?
Authors: Kase Yoshitaka , Shimazaki Takuya , Okano Hideyuki
Published: June 2020

Adult neurogenesis occurs throughout life in restricted brain regions in mammals. However, the number of neural stem cells (NSCs) that generate new neurons steadily decreases with age, resulting in a decrease in neurogenesis. Transplantation of mesenchymal cells or cultured NSCs has been studied as a promising treatment in models of several brain injuries including cerebral infarction and cerebral contusion. Considering the problems of host-versus-graft reactions and the tumorigenicity of transplanted cells, the mobilization of endogenous adult NSCs should be more feasible for the treatment of these brain injuries. However, the number of adult NSCs in the adult brain is limited, and their mitotic potential is low. Here, we outline what we know to date about why the number of NSCs and adult neurogenesis decrease with age. We also discuss issues applicable to regenerative medicine.
Review: transcriptome and trans-omics analysis of systemic lupus erythematosus
Authors: Fujio Keishi , Takeshima Yusuke , Nakano Masahiro , Iwasaki Yukiko
Published: June 2020

Systemic lupus erythematosus (SLE), which was recognized as a defined clinical entity more than 100 years ago, is an archetype for systemic autoimmune diseases. The 10-year survival of SLE patients has shown dramatic improvement during the last half-century. However, SLE patients receiving long-term prednisone therapy are at high risk of morbidity due to organ damage. Identification of key immune pathways is mandatory to develop a suitable therapy and to stratify patients based on their responses to therapy. Recently developed transcriptome and omic analyses have revealed a number of immune pathways associated with systemic autoimmunity. In addition to type I interferon, plasmablast and neutrophil signatures demonstrate associations with the SLE phenotype. Systematic investigations of these findings enable us to understand and stratify SLE according to the clinical and immunological features.
Level of heavy metals in sliced watermelon fruits in selected markets in Akure, Nigeria
Authors: Oladele Oluwole Olakunle , Aladesanmi Omolola Comfort
Published: June 2020

Background

Fruits are increasingly becoming important dietaries in Nigeria because of its nutritional importance and one of the most sliced fruits that are highly purchased in Nigeria today is watermelon. Nevertheless, consumption of heavy metal contaminated fruits could pose a risk to human health. Therefore, the aim of this work was to determine heavy metal contamination in sliced watermelon fruits in selected Nigerian markets to ascertain their public health safety before consumption.

Methods

A total of 54 sliced watermelon fruits were randomly sampled from six different vendors (A –F) in each of the selected markets (Isinkan, Shasha, and Oja-Oba). Samples were digested and analyzed for heavy metal concentrations using atomic absorption spectrometry (AAS) and values compared with WHO (World Health Organization) permissible levels.

Results

The nickel (Ni) levels detected in the sliced fruits across the markets ranged from 0.20 ± 0.01 (Isinkan) to 1.42 ± 0.02 mg kg−1 (Oja-Oba), while chromium (Cr) levels detected ranged from 0.04 ± 0.01 (Shasha) to 0.12 ± 0.02 mg kg−1 (Oja-Oba). Copper (Cu) levels ranged from 0.04 ± 0.00 (Isinkan) to 0.13 ± 0.03 mg kg−1 (Oja-Oba). Remarkably, cadmium and lead were not detected in any of the sliced fruits. Additionally, the levels of Cu in this study were generally below the WHO permissible levels. However, the levels of Ni in all the sliced watermelon fruits, aside the one purchased from vendor D in Isinkan market, were found to be above the permissible levels. Similarly, Cr levels in the sliced fruits purchased only from vendors A, E, and F in Shasha and vendor C in Oja-Oba markets were also found to be above the permissible levels.

Conclusion

This research work provides valuable information on heavy metal contents of sliced watermelon fruits in Akure markets when compared with WHO permissible levels. Fruits with higher values of these metals could constitute health hazards when such fruits are consumed. Hence, there is need to monitor the levels of these metals in sliced fruits from exceeding the acceptable levels as established by regulatory agencies.
Protecting the mental health of healthcare workers during the COVID-19 emergency
Authors: Chirico Francesco , Nucera Gabriella , Magnavita Nicola
Published: June 2020

Healthcare workers employed in the COVID-19 emergency are at high risk of stress, burnout and post-traumatic stress disorders. The most important occupational risk factors that employers should address include insufficient staff training and resources available, and lack of training and treatment protocols. In Italy, recent guidelines were released for providing all healthcare workers who are employed in this emergency with psychological support services based on coping strategies for managing stress. We suggest that preventive measures and a psychological intervention plan should be framed within the mandatory occupational health surveillance programme, and carried out by occupational physicians in cooperation with mental healthcare providers in the workplace.
Emerging Treatment Paradigms for EGFR-Mutant Lung Cancers Progressing on Osimertinib: A Review
Authors: Piper-Vallillo Andrew J. , Sequist Lecia V. , Piotrowska Zofia
Published: June 2020

Since its approval in April 2018, osimertinib has been widely adopted as first-line therapy for patients with advanced EGFR-mutant non -small cell lung cancer (NSCLC). Understanding osimertinib resistance mechanisms and currently available treatment options are essential to selecting optimal second line therapy for patients whose disease progresses during front-line osimertinib. Using data compiled from 6 osimertinib-resistance series, we describe here the heterogeneous profile of EGFR-dependent and independent mechanisms of osimertinib treatment failure. We identified MET alterations (7%-24%), EGFR C797X (0%-29%), SCLC transformation (2%-15%), and oncogene fusions (1%-10%) as the most common mechanisms of resistance. This review provides an evidence-based, algorithmic approach to the evaluation and management of post-osimertinib progression as well as a compendium of active, enrolling clinical trials for this population.
A Systematic Review and Meta-Analysis on the Predictive Value of Cell-Free DNA–Based Androgen Receptor Copy Number Gain in Patients With Castration-Resistant Prostate Cancer
Authors: Tolmeijer Sofie H. , Boerrigter Emmy , Schalken Jack A. , Geerlings Maartje J. , van Oort Inge M. , van Erp Nielka P. , Gerritsen Winald R. , Ligtenberg Marjolijn J.L. , Mehra Niven
Published: June 2020

PURPOSE

It has been suggested that androgen receptor copy number gain ( AR gain) detected in cell-free DNA (cfDNA) can predict treatment response to androgen receptor signaling inhibitors (ARSIs) in patients with castration-resistant prostate cancer (CRPC). But it is unclear whether cfDNA-based AR gain is a true resistance mechanism to ARSIs or mainly a reflection of the tumor burden. In this systematic review, we aim to summarize current literature and comment on the potential of cfDNA-based AR gain as a predictive biomarker to guide therapy choices.

METHODS

A literature search was conducted in PubMed/Medline, Cochrane, Embase, and Web of Science databases. Sixteen articles published before November 2019 were selected for the meta-analysis, representing more than 1,000 patients. By using a random effects model, the progression-free survival (PFS) and overall survival (OS) were compared between patients with and without cfDNA-based AR gain who had been treated with ARSIs or with taxane chemotherapy.

RESULTS

Upon treatment with ARSIs, the PFS (hazard ratio [HR], 2.33; 95% CI, 2.00 to 2.72; P < .0001) and the OS (HR, 3.83; 95% CI, 3.11 to 4.70; P < .0001) were worse for patients with cfDNA-based AR gain, independent of the line and type of ARSIs. The OS and PFS in patients treated with first-line docetaxel or second-line or third-line cabazitaxel seemed to be unaffected by AR gain, despite a higher disease burden in patients with AR gain. AR gain was associated with reduced response with later lines of docetaxel.

CONCLUSION

In patients with CRPC, cfDNA-based AR gain is associated with a worse response to ARSIs. The effect on patients who are receiving taxane chemotherapy seems to be dependent on the type and line, although data are limited. Future prospective studies are essential to assess the true potential of cfDNA-based AR gain as a minimally invasive biomarker to guide therapy choice.
Unmasked Testicular Seminoma During Use of Hormonal Transgender Woman Therapy: A Hidden hCG-Secreting Tumor
Authors: Elshimy Ghada , Tran Kelvin , Harman Sherman M , Correa Ricardo
Published: June 2020

Management of gender-affirming hormone therapy (HT) in transgender women includes surveillance of testosterone (T) levels. Failure of T to suppress, despite adherence to therapy, warrants additional investigations for unexpected sources of T or factors stimulating T secretion. Possible causes include T or gonadotropin production by an occult neoplasm. Testicular cancer is the most common malignancy affecting biological men aged between 15 and 35 years. Patients may be asymptomatic until tumor burden is high and/or metastatic. Hormone-producing tumors have rarely been reported in treated transgender women. Routine screening tests are recommended in a gender-incongruent person as per the 2017 Endocrine Society guidelines with measurement of T levels every 3 months initially to reach a goal of less than 50 ng/dL. Expectations should be discussed in detail with the transgender person since anticipated physical changes may not be notable for 6 to 18 months. We herein describe a case of a transgender woman who underwent standard HT including gonadotropin suppression with a gonadotropin-releasing hormone agonist, whose total T level failed to suppress. Testing revealed an elevated serum level of the beta subunit of human chorionic gonadotropin (β-hCG), diagnostic of an hCG-secreting testicular seminoma, as the underlying cause of unexpected T production. This case illustrates how easily a testicular cancer can remain unnoticed because it can be asymptomatic and the necessity to be alert to, and act on, anomalous laboratory results during treatment of a transgender person.