bluuebunny/crossref_metadata_2025 huggingface dataset:
Malaria distribution and performance of malaria diagnostic methods in Malaysia (1980–2019): a systematic review
Authors: Rahim Mohd Amirul Fitri A. , Munajat Mohd Bakhtiar , Idris Zulkarnain Md
Published: November 2020

Background

Malaysia has already achieved remarkable accomplishments in reaching zero indigenous human malaria cases in 2018. Prompt malaria diagnosis, surveillance and treatment played a key role in the country’s elimination success. Looking at the dynamics of malaria distribution during the last decades might provide important information regarding the potential challenges of such an elimination strategy. This study was performed to gather all data available in term of prevalence or incidence on Plasmodium infections in Malaysia over the last four decades.

Methods

A systematic review of the published English literature was conducted to identify malaria distribution from 1980 to June 2019 in Malaysia. Two investigators independently extracted data from PubMed, Scopus, Web of Science and Elsevier databases for original papers.

Results

The review identified 46 epidemiological studies in Malaysia over the 39-year study period, on which sufficient information was available. The majority of studies were conducted in Malaysia Borneo (31/46; 67.4%), followed by Peninsular Malaysia (13/46; 28.3%) and in both areas (2/46; 4.3%). More than half of all studies (28/46; 60.9%) were assessed by both microscopy and PCR. Furthermore, there was a clear trend of decreases of all human malaria species with increasing Plasmodium knowlesi incidence rate throughout the year of sampling period. The summary estimates of sensitivity were higher for P. knowlesi than other Plasmodium species for both microscopy and PCR. Nevertheless, the specificities of summary estimates were similar for microscopy (40–43%), but varied for PCR (2–34%).

Conclusions

This study outlined the epidemiological changes in Plasmodium species distribution in Malaysia. Malaria cases shifted from predominantly caused by human malaria parasites to simian malaria parasites, which accounted for the majority of indigenous cases particularly in Malaysia Borneo. Therefore, malaria case notification and prompt malaria diagnosis in regions where health services are limited in Malaysia should be strengthened and reinforced to achieving the final goal of malaria elimination in the country.
Hyperlipidemia and mortality associated with diabetes mellitus co-existence in Chinese peritoneal dialysis patients
Authors: Wei Xin , Wen Yueqiang , Zhou Qian , Feng Xiaoran , Peng Fen Fen , Wang Niansong , Wang Xiaoyang , Wu Xianfeng
Published: November 2020

Background

To evaluate associations between diabetes mellitus (DM) coexisting with hyperlipidemia and mortality in peritoneal dialysis (PD) patients.

Methods

This was a retrospective cohort study with 2939 incident PD patients in China from January 2005 to December 2018. Associations between the DM coexisting with hyperlipidemia and mortality were evaluated using the Cox regression.

Results

Of 2939 patients, with a median age of 50.0 years, 519 (17.7%) died during the median of 35.1 months. DM coexisting with hyperlipidemia, DM, and hyperlipidemia were associated with 1.93 (95% CI 1.45 to 2.56), 1.86 (95% CI 1.49 to 2.32), and 0.90 (95% CI 0.66 to 1.24)-time higher risk of all-cause mortality, compared with without DM and hyperlipidemia, respectively (Pfor trend < 0.001). Subgroup analyses showed a similar pattern. Among DM patients, hyperlipidemia was as a high risk of mortality as non-hyperlipidemia (hazard ratio 1.02, 95%CI 0.73 to 1.43) during the overall follow-up period, but from 48-month follow-up onwards, hyperlipidemia patients had 3.60 (95%CI 1.62 to 8.01)-fold higher risk of all-cause mortality than those non-hyperlipidemia (Pinteraction = 1.000).

Conclusions

PD patients with DM coexisting with hyperlipidemia were at the highest risk of all-cause mortality, followed by DM patients and hyperlipidemia patients, and hyperlipidemia may have an adverse effect on long-term survival in DM patients.
Brain metastases-derived extracellular vesicles induce binding and aggregation of low-density lipoprotein
Authors: Busatto Sara , Yang Yubo , Walker Sierra A. , Davidovich Irina , Lin Wan-Hsin , Lewis-Tuffin Laura , Anastasiadis Panagiotis Z. , Sarkaria Jann , Talmon Yeshayahu , Wurtz Gregory , Wolfram Joy
Published: November 2020

Background

Cancer cell-derived extracellular vesicles (EVs) have previously been shown to contribute to pre-metastatic niche formation. Specifically, aggressive tumors secrete pro-metastatic EVs that travel in the circulation to distant organs to modulate the microenvironment for future metastatic spread. Previous studies have focused on the interface between pro-metastatic EVs and epithelial/endothelial cells in the pre-metastatic niche. However, EV interactions with circulating components such as low-density lipoprotein (LDL) have been overlooked.

Results

This study demonstrates that EVs derived from brain metastases cells (Br-EVs) and corresponding regular cancer cells (Reg-EVs) display different interactions with LDL. Specifically, Br-EVs trigger LDL aggregation, and the presence of LDL accelerates Br-EV uptake by monocytes, which are key components in the brain metastatic niche.

Conclusions

Collectively, these data are the first to demonstrate that pro-metastatic EVs display distinct interactions with LDL, which impacts monocyte internalization of EVs.
Superparamagnetic iron oxide nanoparticles conjugated with Aβ oligomer-specific scFv antibody and class A scavenger receptor activator show therapeutic potentials for Alzheimer’s Disease
Authors: Liu Xiao-ge , Zhang Lun , Lu Shuai , Liu Dong-qun , Huang Ya-ru , Zhu Jie , Zhou Wei-wei , Yu Xiao-lin , Liu Rui-tian
Published: November 2020

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. No disease-modifying strategy to prevent or delay AD progression currently exists. Aβ oligomers (AβOs), rather than monomers or fibrils, are considered as the primary neurotoxic species. Therapeutic approaches that direct against AβOs and promote Aβ clearance may have great value for AD treatment.

Results

We here reported a multifunctional superparamagnetic iron oxide nanoparticle conjugated with Aβ oligomer-specific scFv antibody W20 and class A scavenger receptor activator XD4 (W20/XD4-SPIONs). Besides the diagnostic value, W20/XD4-SPIONs retained the anti-Aβ properties of W20 and XD4 by inhibiting Aβ aggregation, attenuating AβO-induced cytotoxicity and increasing microglial phagocytosis of Aβ. When applied to APP/PS1 mice, W20/XD4-SPIONs significantly rescued cognitive deficits and alleviated neuropathology of AD mice.

Conclusion

These results suggest that W20/XD4-SPIONs show therapeutic benefits for AD. In combination with the early diagnostic property, W20/XD4-SPIONs present as a promising agent for early-stage AD diagnosis and intervention.
An endoscopic dilation method using the rendezvous approach for the treatment of severe anastomotic stenosis after rectal cancer surgery: a case report
Authors: Nakashima Takuya , Matsuhashi Nobuhisa , Suetsugu Tomonari , Iwata Yoshinori , Kiyama Shigeru , Takahashi Takao , Masahiro Fukada , Yasufuku Itaru , Sato Yuta , Imai Takeharu , Tanaka Yoshihiro , Okumura Naoki , Kubota Masaya , Ibuka Takashi , Shimizu Masato , Yoshida Kazuhiro
Published: November 2020

Background

Postoperative anastomotic stenosis is a common complication in colorectal cancer patients (3–30%). Complete anastomotic stenosis is rare; however, when it occurs, almost all cases require surgical treatment. We herein report a case in which endoscopic dilation was effective for treating complete anastomotic stenosis after high anterior resection in a rectal cancer patient.

Case presentation

The patient was a 67-year-old man who underwent laparoscopic high anterior resection for rectal cancer (RS, T4a, N0, M0, Stage IIB (TNM Classification of Malignant Tumors)) in May 2018. The postoperative course was good and the patient was discharged on the 12th postoperative day. Subsequently adjuvant chemotherapy was initiated with oral uracil and tegafur plus leucovorin (UFT/LV); however, he complained of frequent defecation and melena after completion of the first course of chemotherapy. Thus, colonoscopy was performed, which revealed anastomotic stenosis. Endoscopic dilation was initially attempted, but failed. Thus, low anterior resection was performed with diverting colostomy. Four additional courses of chemotherapy were administered for 1 month after surgery. At 6 months after the second surgery, colonoscopy was performed, and complete anastomotic stenosis was pointed out again. The patient was successfully treated by endoscopic dilation using the rendezvous method. After this treatment, the lumen of the anastomotic site was observed to have narrowed again and endoscopic dilatation to treat anastomotic stenosis was repeated. In addition, he received local injection of steroids in anastomotic stenosis site. The lumen of anastomotic stenosis remained after the local injection of steroids and closure of colostomy was performed 9 months after the second operation.

Conclusions

Endoscopic dilation using the rendezvous method was effective for treating anastomotic stenosis after colorectal surgery.
Cost-effectiveness analysis of ceritinib vs. crizotinib in previously untreated anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in Hong Kong
Authors: Loong Herbert H. , Wong Carlos K. H. , Leung Linda K. S. , Chan Catherine P. K. , Chang Andrea , Zhou Zheng-Yi , Xie Jipan , Gibbs Meaghan
Published: November 2020

Introduction

Lower-dose ceritinib (450 mg) once-daily with food was approved in 2018 in Hong Kong (HK) for first-line treatment of patients with anaplastic lymphoma kinase-positive (ALK +) advanced non-small cell lung cancer (NSCLC). This study examined the cost-effectiveness of ceritinib vs. crizotinib in the first-line treatment of ALK + NSCLC from a HK healthcare service provider's or government's perspective.

Methods

Costs and effectiveness of first-line ceritinib vs. crizotinib over a 20-year time horizon was evaluated using a partitioned survival model with three health states (stable disease, progressed disease, and death). The efficacy data for ceritinib were obtained from a phase 3 trial comparing ceritinib with chemotherapy for advanced non-small cell lung cancer (ASCEND-4) and extrapolated using parametric survival models. Long-term survival associated with crizotinib were estimated using hazard ratio of crizotinib vs. ceritinib obtained from matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014 trials. Drug acquisition, administration, adverse events costs, and medical costs associated with each health state were obtained from public sources and converted to 2018 US Dollars. Incremental costs per quality-adjusted-life-year (QALY) and life-year (LY) gained were estimated for ceritinib vs. crizotinib.

Results

The base case results showed that ceritinib was associated with 3.22 QALYs, 4.51 LYs, and total costs of $157,581 over 20 years. Patients receiving crizotinib had 2.68 QALYs, 3.85 LYs, and $150,424 total costs over the same time horizon. The incremental cost per QALY gained for ceritinib vs crizotinib was $13,343. Results were robust to deterministic sensitivity analyses in most scenarios.

Conclusion

Ceritinib offers a cost-effective option compared to crizotinib for previously untreated ALK + advanced NCSLC in HK.
Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection
Authors: Li Xiaoyi , Zhang Qifan , Zhang Wanyue , Ye Guofu , Ma Yanchen , Wen Chunhua , Gu Shuqin , Tang Libo , Li Yongyin
Published: November 2020

Background

The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection.

Methods

The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells.

Results

We observed that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared to that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, positive correlations were observed between the frequencies of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells. Notably, in vitro experimental results demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells.

Conclusions

Expanded FDCs in patients with chronic HBV infection may favor host immune responses against HBV. The identification of this unique population of cell may contribute to a better understanding of the immune regulatory mechanisms associated with chronic HBV infection and provide a potential immunotherapeutic target for this disease.
Identification of cancer stem cell-related biomarkers in intestinal-type and diffuse-type gastric cancer by stemness index and weighted correlation network analysis
Authors: Guo Rui , Chu Aining , Gong Yuehua
Published: November 2020

Background

Cancer stem cells (CSCs) play an important role in drug resistance, recurrence, and metastasis of tumors. Considering the heterogeneity of tumors, this study aimed to explore the key genes regulating stem cells in intestinal-type and diffuse-type gastric cancer.

Methods

RNA-seq data and related clinical information were downloaded from The Cancer Genome Atlas (TCGA). WGCNA was used to clustered differentially expressed genes with similar expression profiles to form modules. Furtherly, based on the mRNA expression-based stemness index (mRNAsi), significant modules and key genes were identified. Next, the expression of key genes was further verified by the Oncomine database.

Results

MRNAsi scores of GC were significantly higher than that of normal tissue. Additionally, mRNAsi scores of intestinal-type GC (IGC) were significantly higher than that of diffuse-type GC (DGC). WGCNA showed that the blue module of IGC and the brown module of DGC were both the most significantly associated with mRNAsi. We screened out 16 and 43 key genes for IGC and DGC and found that these genes were closely related, respectively. Functional analysis showed the relationship between the key genes confirmed in the Oncomine database and the fate of cells.

Conclusions

In this study, 16 and 43 genes related to the characteristics of CSCs were identified in IGC and DGC, respectively. These genes were both associated with cell cycle, which could serve as therapeutic targets for the inhibition of stem cells from both types of GC.
COVID-19: Is there a role for immunonutrition in obese patient?
Authors: Di Renzo Laura , Gualtieri Paola , Pivari Francesca , Soldati Laura , Attinà Alda , Leggeri Claudia , Cinelli Giulia , Tarsitano Maria Grazia , Caparello Giovanna , Carrano Elena , Merra Giuseppe , Pujia Alberto Maria , Danieli Roberta , De Lorenzo Antonino
Published: November 2020

On December 12, 2019 a new coronavirus (SARS-CoV-2) emerged in Wuhan, China, triggering a pandemic of severe acute respiratory syndrome in humans (COVID-19). Today, the scientific community is investing all the resources available to find any therapy and prevention strategies to defeat COVID-19. In this context, immunonutrition can play a pivotal role in improving immune responses against viral infections. Immunonutrition has been based on the concept that malnutrition impairs immune function. Therefore, immunonutrition involves feeding enriched with various pharmaconutrients (Omega 3 Fatty Acids, Vitamin C, Arginine, Glutamine, Selenium, Zinc, Vitamin, E and Vitamin D) to modulate inflammatory responses, acquired immune response and to improve patient outcomes. In literature, significant evidences indicate that obesity, a malnutrition state, negatively impacts on immune system functionality and on host defense, impairing protection from infections. Immunonutrients can promote patient recovery by inhibiting inflammatory responses and regulating immune function. Immune system dysfunction is considered to increase the risk of viral infections, such as SARS-CoV-2, and was observed in different pathological situations. Obese patients develop severe COVID-19 sequelae, due to the high concentrations of TNF-α, MCP-1 and IL-6 produced in the meantime by visceral and subcutaneous adipose tissue and by innate immunity. Moreover, leptin, released by adipose tissue, helps to increase inflammatory milieu with a dysregulation of the immune response. Additionally, gut microbiota plays a crucial role in the maturation, development and functions of both innate and adaptive immune system, as well as contributing to develop obese phenotype. The gut microbiota has been shown to affect lung health through a vital crosstalk between gut microbiota and lungs, called the “gut-lung axis”. This axis communicates through a bi-directional pathway in which endotoxins, or microbial metabolites, may affect the lung through the blood and when inflammation occurs in the lung, this in turn can affect the gut microbiota. Therefore, the modulation of gut microbiota in obese COVID-19 patients can play a key role in immunonutrition therapeutic strategy. This umbrella review seeks to answer the question of whether a nutritional approach can be used to enhance the immune system’s response to obesity in obese patients affected by COVID-19.
Work and breast milk feeding: a qualitative exploration of the experience of lactating mothers working in ready made garments factories in urban Bangladesh
Authors: Hasan A M Rumayan , Smith George , Selim Mohammad Abdus , Akter Shahinoor , Khan Nazib Uz Zaman , Sharmin Tamanna , Rasheed Sabrina
Published: November 2020

Background

In Bangladesh 65% of children under 6 months of age were exclusively breastfed with maternal employment being a risk factor that has jeopardized exclusive breastfeeding. As Ready Made Garment (RMG) factories have been the largest employer of low income women in Bangladesh, the objective of our study was to explore the barriers and facilitators of breastfeeding and perceptions about use of expressed breast milk among mothers who worked in the RMG sector.

Methods

This formative research was conducted during July–September 2015 in two slums of Dhaka among RMG workers who were mothers and the caregivers of 0–12 month old infants. Qualitative data was obtained from purposively selected participants of 8 in-depth interviews and 4 focus group discussions (mothers and caregivers), and 2 key informant (RMG factory official) interviews. Mothers were from multiple RMG factories while factory officials were from a single factory. Thematic analysis was conducted.

Results

The main themes of qualitative exploration were knowledge and experience of breastfeeding; structural barriers (home and workplace); consequences of inadequate breastfeeding; and perception and experience of using expressed breast milk. Despite knowledge both of the benefits of breast milk and of the importance of breastfeeding for 6 months, most mothers introduced formula as early as 2 months to prepare for their return to work. Barriers such as excessive workload, inadequate crèche facilities at work, and lack of adequate caregivers at home impeded exclusive breastfeeding. Mothers and caregivers had very little knowledge about the use of expressed breast milk and were concerned about contamination.

Conclusion

As RMG factories are the largest employer of low-income women in Bangladesh, facilitating RMG factory working mothers’ ability to use breast milk could help to promote infant health and help women remain in the workforce.
The decreased mean platelet volume is associated with poor prognosis in patients with oropharyngeal cancer treated with radiotherapy
Authors: Delago Daniela , Knittelfelder Olivia , Jakse Gabriele , Lukasiak Katarzyna , Reinisch Sabine , Renner Wilfried , Stranzl-Lawatsch Heidi , Partl Richard , Langsenlehner Tanja
Published: November 2020

Background

There is considerable evidence that platelets contribute to cancer growth and metastatic dissemination. In recent studies, altered mean platelet volume (MPV) has been associated with prognosis in different types of cancer. However, the prognostic role of the MPV in head and neck squamous cell cancer (HNSCC) is currently discussed controversially. The present study was performed to analyze and further elucidate the prognostic significance of the MPV in HNSCC.

Methods

A total of 319 oropharyngeal squamous cell cancer (OPSCC) patients treated with radiotherapy at a tertiary academic center were enrolled in the present study. Kaplan–Meier method as well as uni- and multivariate Cox proportional hazards were used to evaluate the impact of MPV on cancer-specific survival (CSS), locoregional control (LC) and recurrence-free survival (RFS).

Results

The median MPV was 10.30 fL (mean 10.26 ± 1.17fL). Univariate analyses showed a significant association of the MPV with CSS (HR 0.85, 95% CI 0.74–0.98, p = 0.025), LC (HR 0.86, 95% CI 0.74–0.99, p = 0.034) and RFS (HR 0.87, 95% CI 0.76–0.996; p = 0.043). In multivariate analysis, the MPV remained an independent prognostic factor for CSS (HR 0.77, 95% CI 0.63–0.93, p = 0.008), LC (HR 0.80, 95% CI 0.65–0.98, p = 0.030), and RFS (HR 0.83, 95% CI 0.685–0.999, p = 0.049).

Conclusions

Our findings indicate that the MPV is a prognostic marker in OPSCC patients and may contribute to future individual risk assessment.
Survival and diagnostic age of 175 Taiwanese patients with mucopolysaccharidoses (1985–2019)
Authors: Lin Hsiang-Yu , Lee Chung-Lin , Chang Chia-Ying , Chiu Pao Chin , Chien Yin-Hsiu , Niu Dau-Ming , Tsai Fuu-Jen , Hwu Wuh-Liang , Lin Shio Jean , Lin Ju-Li , Chao Mei-Chyn , Chang Tung-Ming , Tsai Wen-Hui , Wang Tzu-Jou , Chuang Chih-Kuang , Lin Shuan-Pei
Published: November 2020

Background

Mucopolysaccharidoses (MPSs) are a group of inherited metabolic diseases, which are characterized by the accumulation of glycosaminoglycans, and eventually lead to the progressive damage of various tissues and organs.

Methods

An epidemiological study of MPS in Taiwan was performed using multiple sources. The survival and diagnostic age for different types of MPS between 1985 and 2019 were evaluated.

Results

Between 1985 and 2019, there were 175 patients diagnosed with MPS disorders in the Taiwanese population, with a median diagnostic age of 3.9 years. There were 21 (12%), 78 (45%), 33 (19%), 32 (18%) and 11 (6%) patients diagnosed with MPS I, II, III, IV and VI, respectively, with median diagnostic ages of 1.5, 3.8, 4.7, 4.5 and 3.7 years, respectively. Diagnosis of MPS patients was significantly earlier in recent decades (p < 0.01). Pilot newborn screening programs for MPS I, II, VI, IVA, and IIIB were progressively introduced in Taiwan from 2016, and 48% (16/33) of MPS patients diagnosed between 2016 and 2019 were diagnosed by one of these screening programs, with a median diagnostic age at 0.2 years. For patients born between 2016 and 2019, up to 94% (16/17) were diagnosed with MPS via the newborn screening programs. At the time of this study, 81 patients had passed away with a median age at death of 15.6 years. Age at diagnosis was positively correlated with life expectancy (p < 0.01). Life expectancy also significantly increased between 1985 and 2019, however this increase was gradual (p < 0.01).

Conclusions

The life expectancy of Taiwanese patients with MPS has improved in recent decades and patients are being diagnosed earlier. Because of the progressive nature of the disease, early diagnosis by newborn screening programs and timely implementation of early therapeutic interventions may lead to better clinical outcomes.
Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer
Authors: Chen Hengyu , Deng Qingchun , Wang Wenwen , Tao Huishan , Gao Ying
Published: November 2020

Cervical cancer is one of the most common female malignancy that occurs worldwide and is reported to cause over 300,000 deaths in 2018. Autophagy controls the survival and death of cancerous cells by regulating the degradation process of cytoplasm and cellular organelle. In the present study, the differentially expressed autophagy-related genes (ARGs) between healthy and cancerous cervical tissues (squamous cell neoplasms) were obtained using data from GTEx and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology (GO) as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Next, we conducted univariate Cox regression assay and obtained 12 ARGs that were associated with the prognosis of cervical cancer patients. We carried out a multivariate Cox regression analysis and developed six ARG-related prognostic signature for the survival prediction of patients with squamous cell cervical cancer (Risk score = − 0.63*ATG3–0.42*BCL2 + 0.85*CD46–0.38*IFNG+ 0.23*NAMPT+ 0.82*TM9SF1). Following the calculation of risk score using the signature, the patients were divided into high and low-risk groups according to the median value. Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis (P < 0.001). The value for area under the curves corresponding to the receiver operating characteristic (ROC) was 0.740. As observed, the expression of IFNG was negatively associated with lymph node metastasis (P = 0.026), while a high-risk score was significantly associated with increased age (P = 0.008). To further validate the prognostic signature, we carried out a permutation test and confirmed the performance of the risk score. In conclusion, our study developed six ARG-related prognostic signature for patients with squamous cell cervical cancer, which might help in improving the prognostic predictions of such patients.
Performance of the cuff leak test in adults in predicting post-extubation airway complications: a systematic review and meta-analysis
Authors: Kuriyama Akira , Jackson Jeffrey L. , Kamei Jun
Published: November 2020

Background

Clinical practice guidelines recommend performing a cuff leak test in mechanically ventilated adults who meet extubation criteria to screen those at high risk for post-extubation stridor. Previous systematic reviews demonstrated excellent specificity of the cuff leak test but disagreed with respect to sensitivity. We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of the cuff leak test for predicting post-extubation airway complications in intubated adult patients in critical care settings.

Methods

We searched Medline, EMBASE, Scopus, ISI Web of Science, the Cochrane Library for eligible studies from inception to March 16, 2020, without language restrictions. We included studies that examined the diagnostic accuracy of cuff leak test if post-extubation airway obstruction after extubation or reintubation was explicitly reported as the reference standard. Two authors in duplicate and independently assessed the risk of bias using the Quality Assessment for Diagnostic Accuracy Studies-2 tool. We pooled sensitivities and specificities using generalized linear mixed model approach to bivariate random-effects meta-analysis. Our primary outcomes were post-extubation airway obstruction and reintubation.

Results

We included 28 studies involving 4493 extubations. Three studies were at low risk for all QUADAS-2 risk of bias domains. The pooled sensitivity and specificity of cuff leak test for post-extubation airway obstruction were 0.62 (95% CI 0.49–0.73;I2 = 81.6%) and 0.87 (95% CI 0.82–0.90;I2 = 97.8%), respectively. The pooled sensitivity and specificity of the cuff leak test for reintubation were 0.66 (95% CI 0.46–0.81;I2 = 48.9%) and 0.88 (95% CI 0.83–0.92;I2 = 87.4%), respectively. Subgroup analyses suggested that the type of cuff leak test and length of intubation might be the cause of statistical heterogeneity of sensitivity and specificity, respectively, for post-extubation airway obstruction.

Conclusions

The cuff leak test has excellent specificity but moderate sensitivity for post-extubation airway obstruction. The high specificity suggests that clinicians should consider intervening in patients with a positive test, but the low sensitivity suggests that patients still need to be closely monitored post-extubation.
Modeling and simulation of the spatial population dynamics of the Aedes aegypti mosquito with an insecticide application
Authors: Silva Monalisa R. , Lugão Pedro H. G. , Chapiro Grigori
Published: November 2020

Background

The Aedes aegypti mosquito is the primary vector for several diseases. Its control requires a better understanding of the mosquitoes’ live cycle, including the spatial dynamics. Several models address this issue. However, they rely on many hard to measure parameters. This work presents a model describing the spatial population dynamics of Aedes aegypti mosquitoes using partial differential equations (PDEs) relying on a few parameters.

Methods

We show how to estimate model parameter values from the experimental data found in the literature using concepts from dynamical systems, genetic algorithm optimization and partial differential equations. We show that our model reproduces some analytical formulas relating the carrying capacity coefficient to experimentally measurable quantities as the maximum number of mobile female mosquitoes, the maximum number of eggs, or the maximum number of larvae. As an application of the presented methodology, we replicate one field experiment numerically and investigate the effect of different frequencies in the insecticide application in the urban environment.

Results

The numerical results suggest that the insecticide application has a limited impact on the mosquitoes population and that the optimal application frequency is close to one week.

Conclusions

Models based on partial differential equations provide an efficient tool for simulating mosquitoes’ spatial population dynamics. The reduced model can reproduce such dynamics on a sufficiently large scale.
Significant reduction in abundance of peridomestic mosquitoes (Culicidae) and Culicoides midges (Ceratopogonidae) after chemical intervention in western São Paulo, Brazil
Authors: González Mikel A. , Dilger Erin , Ronderos María M. , Spinelli Gustavo R. , Courtenay Orin , Hamilton James G. C.
Published: November 2020

Background

We assessed the impact of two sand fly insecticide interventions (insecticide spraying and insecticide-impregnated dog collars) on the peridomestic abundance and distribution of mosquitoes (Culicidae) and biting midges (Ceratopogonidae) in western São Paulo (Brazil) in a long-term (42-month) evaluation. Both of these dipteran groups are vectors of diseases of medical and veterinary relevance to humans and domestic animals in Brazil.

Methods

The interventions in the 3-arm stratified randomised control trial were: pheromone + insecticide (PI) (chicken roosts were sprayed with microencapsulated lambda-cyhalothrin; pheromone lure has no effect on the Diptera pests studied here); dog-collars (DC) (dogs fitted with deltamethrin-impregnated collars); and control (C) (unexposed to pyrethroids) were extended by 12 months. During that time, adult mosquitoes and midges were sampled along 280 households at three household locations (inside human dwellings, dog sleeping sites and chicken roosts).

Results

We collected 3145 culicids (9 genera, 87.6%Culexspp.) distributed relatively uniformly across all 3 arms: 41.9% at chicken roosts; 37.7% inside houses; and 20.3% at dog sleeping sites. We collected 11,464Culicoides(15 species) found mostly at chicken roosting sites (84.7%) compared with dog sleeping sites (12.9%) or houses (2.4%). Mosquitoes andCulicoideswere most abundant during the hot and rainy season. Increased daytime temperature was marginally associated with increased mosquito abundance (Z = 1.97,P = 0.049) andCulicoidesabundance (Z = 1.71,P = 0.087). There was no significant association with daily average rainfall for either group. Household-level mosquito and midge numbers were both significantly reduced by the PI intervention 56% [incidence rate ratio, IRR = 0.54 (95% CI: 0.30–0.97),P ≤ 0.05] and 53% [IRR = 0.47 (95% CI: 0.26–0.85),P ≤ 0.05], respectively, compared to the control intervention. The abundance of both dipteran groups at dog sleeping sites was largely unaffected by the PI and DC interventions. The PI intervention significantly reduced abundance of mosquitoes inside houses (41%) and at chicken roosting sites (48%) and reduced midge abundance by 51% in chicken roosting sites.

Conclusions

Sprayed insecticide at chicken roosting sites reduced the abundance of mosquitoes and midges at the peridomestic level while dog collars had no effect on numbers for any group.
Serum inflammatory and oxidative stress biomarkers levels are associated with pain intensity, pressure pain threshold and quality of life in myofascial pain syndrome
Authors: Shakouri Seyed Kazem , Dolatkhah Neda , Omidbakhsh Sepideh , Pishgahi Alireza , Hashemian Maryam
Published: November 2020

Objectives

We aimed to determine the serum concentrations of some inflammatory and oxidative stress biomarkers in relation with pain intensity and quality of life in patients with myofascial pain syndrome (MPS) compared to healthy controls. This study is a case–control study. The participants were selected from MPS patients who referred to rehabilitation outpatient clinics of the Tabriz University of Medical Sciences, Iran.

Results

Serum hs-CRP (4.68 ± 4.36 vs. 2.92 ± 4.55 g/mlµ respectively, p = 0.011), phospholipase A2 (PLA2) (6.81 ± 2.22 vs. 4.73 ± 2.97 pg/ml respectively, p < 0.001) and malondialdehyde (MDA) (2.63 ± 0.71 vs. 1.98 ± 0.90 nmol/ml respectively, p < 0.001) levels were significantly higher and serum total antioxidant capacity (TAC) (2.46 ± 0.49 vs. 2.83 ± 0.82 mmol/L respectively, p = 0.011) and superoxide dismutase (SOD) (78.89 ± 37.93 vs. 154.25 ± 115.93 U/ml respectively, p < 0.001) levels were significantly lower in the MPS patients compared to healthy controls. Serum high-sensitivity C-reactive protein (hs-CRP) level was significantly and positively associated with resting (r = 0.349, p = 0.019), activity (r = 0.295, p = 0.049) and night pain (r = 0.304, p = 0.043) intensities, pressure pain threshold (PPT) (r = 0.210, p = 0.047) and pain duration (r = 0.283, p = 0.007). Serum TAC level was significantly and negatively associated with resting pain intensity (r = −0.312, p = 0.037). Some scales and subscales of quality of life were positively correlated with serum TAC level and negatively associated with serum hs-CRP and PLA2 levels.
Risk of pre-term births and major birth defects resulting from paternal intake of COVID-19 medications prior to conception
Authors: Rizzi Silvia , Wensink Maarten J. , Lindahl-Jacobsen Rune , Tian Lu , Lu Ying , Eisenberg Michael L.
Published: November 2020

Objective

With the ongoing COVID-19 pandemic, large numbers of people will receive one of the several medications proposed to treat COVID-19, including patients of reproductive age. Given that some medications have shown adverse effects on sperm quality, there might be a transgenerational concern. We aim at examining the association between drugs proposed to treat COVID-19 when taken by the father around conception and any pre-term birth or major birth defects in offspring in a nation-wide cohort study using Danish registry data. Offspring whose father filled at least one prescription of the following medications in the 3 months preceding conception were considered exposed: chloroquine, hydroxychloroquine, losartan, azithromycin, naproxen, dexamethasone and prednisone.

Results

For azithromycin and naproxen, large numbers of offspring were exposed (> 1800 offspring), and we found no association with adverse birth outcomes. For chloroquine, losartan and dexamethasone, exposure was intermediate (~ 900 offspring), and there was no statistically significant association with birth defects. For hydroxychloroquine and prednisone, exposure was limited (< 300 offspring). Our evidence suggests that azithromycin and naproxen are safe with respect to pre-term birth and birth defects. For the other drugs investigated larger exposures are needed for conclusive statements.
A snapshot of Plasmodium falciparum malaria drug resistance markers in Sudan: a pilot study
Authors: Mohamed Nouh S. , Abdelbagi Hanadi , Osman Hussam A. , Ahmed Abdallah E. , Yousif Alaa M. , Edris Yusraa B. , Osman Eman Y. , Elsadig Aahd R. , Siddig Emmanuel E. , Mustafa Madinna , Mohammed Ammar A. , Ali Yousif , Osman Maha M. , Ali Mohamed S. , Omer Rihab A. , Ahmed Ayman , Sibley Carol H.
Published: November 2020

Objectives

Malaria infection is still known to be a worldwide public health problem, especially in tropical and sub-tropical African countries like Sudan. A pilot study conducted to describe the trend ofP. falciparumdrug resistance markers in 2017–2018 in comparison to CQ and AS/SP eras in Sudan. ThePfcrt,Pfmdr-1,Pfdhfr, andPfdhpsgenes were investigated. Data deposited by the worldwide antimalarial resistance network was consulted, and the molecular markers previously reported from Sudan were analyzed.

Results

Drug molecular markers analysis was successfully done on 20P. falciparumisolates. ThePfcrtK76 showed high frequency; 16 (80%). For thePfmdr-1,9 (45%) isolates were carrying the N86 allele, and 11 (55%) were 86Y allele. While the Y184F of thePfmdr-1showed a higher frequency of 184F compared to Y184; 16 (80%) and 4 (20%), respectively. In thePfdhfr, 51I allele showed higher frequency compared to N51; 18 (90%) and 2 (10%), respectively. For S108N, 18 (90%) were 108 N and 2 (10%) were S108. In thePfdhps, all isolates were carrying the mutant alleles; 437G and 540E. The frequency distribution of thePfcrt,Pfmdr-1,Pfdhfr,Pfdhpswas significantly different across the whole years in Sudan.
Assessing the effects of exposure to a SARS-CoV-2 re-positive patient in healthcare personnel
Authors: Ogawa Yoshihiko , Nishida Koji , Gohma Iwao , Kasahara Kei , Yano Hisakazu
Published: November 2020

Objective

To evaluate whether patients with COVID-19 who have tested re-positive with the PCR test for the SARS-CoV-2 virus are infectious is a challenge in the current circumstances. A follow-up survey was conducted with healthcare personnel (HCP) who were exposed to a patient whose PCR test results for SARS-CoV-2 were re-positive 18 days after the initial confirmation of negative PCR results.

Results

We studied a total of 15 HCP who had contact exposures (15/15) and aerosol exposures (7/15). None of them tested positive for IgG against SARS-CoV-2 on blood examination. None of them had any symptoms during 10 days of active isolation. All PCR tests conducted using the nasopharyngeal swabs collected from the HCP on day 10 were negative. No apparent infection was found in any of the HCP who had contact exposure with and/or aerosol exposure to the patient whose PCR test results for SARS-CoV-2 were re-positive 18 days after the initial confirmation of negative results of PCR tests for SARS-CoV-2.

Clinical trial: Trial Registration: No. 170, approved June 10th, 2020 by the ethics committee of Sakai City Medical Center.
Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma
Authors: Zhang Ping , Zhang Mingzhi
Published: November 2020

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of clinically aggressive diseases associated with poor prognosis. Except for ALK + anaplastic large-cell lymphoma (ALCL), most peripheral T-cell lymphomas are highly malignant and have an aggressive disease course and poor clinical outcomes, with a poor remission rate and frequent relapse after first-line treatment. Aberrant epigenetic alterations play an important role in the pathogenesis and development of specific types of peripheral T-cell lymphoma, including the regulation of the expression of genes and signal transduction. The most common epigenetic alterations are DNA methylation and histone modification. Histone modification alters the level of gene expression by regulating the acetylation status of lysine residues on the promoter surrounding histones, often leading to the silencing of tumour suppressor genes or the overexpression of proto-oncogenes in lymphoma. DNA methylation refers to CpG islands, generally leading to tumour suppressor gene transcriptional silencing. Genetic studies have also shown that some recurrent mutations in genes involved in the epigenetic machinery, including TET2, IDH2-R172, DNMT3A, RHOA, CD28, IDH2, TET2, MLL2, KMT2A, KDM6A, CREBBP, and EP300, have been observed in cases of PTCL. The aberrant expression of miRNAs has also gradually become a diagnostic biomarker. These provide a reasonable molecular mechanism for epigenetic modifying drugs in the treatment of PTCL. As epigenetic drugs implicated in lymphoma have been continually reported in recent years, many new ideas for the diagnosis, treatment, and prognosis of PTCL originate from epigenetics in recent years. Novel epigenetic-targeted drugs have shown good tolerance and therapeutic effects in the treatment of peripheral T-cell lymphoma as monotherapy or combination therapy. NCCN Clinical Practice Guidelines also recommended epigenetic drugs for PTCL subtypes as second-line therapy. Epigenetic mechanisms provide new directions and therapeutic strategies for the research and treatment of peripheral T-cell lymphoma. Therefore, this paper mainly reviews the epigenetic changes in the pathogenesis of peripheral T-cell lymphoma and the advancement of epigenetic-targeted drugs in the treatment of peripheral T-cell lymphoma (PTCL).
Cognitive training and brain stimulation in prodromal Alzheimer’s disease (AD-Stim)—study protocol for a double-blind randomized controlled phase IIb (monocenter) trial
Authors: Thams Friederike , Kuzmina Anna , Backhaus Malte , Li Shu-Chen , Grittner Ulrike , Antonenko Daria , Flöel Agnes
Published: November 2020

Background

Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer’s disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stimulation (tDCS) to be an effective method to boost cognitive performance, especially when applied in combination with cognitive training in healthy older adults. So far, no studies combining tDCS concurrent with an intense multi-session cognitive training in prodromal AD populations have been conducted.

Methods

The AD-Stim trial is a monocentric, randomized, double-blind, placebo-controlled study, including a 3-week tDCS-assisted cognitive training with anodal tDCS over left DLPFC (target intervention), compared to cognitive training plus sham (control intervention). The cognitive training encompasses a letter updating task and a three-stage Markov decision-making task. Forty-six participants with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) will be randomized block-wise to either target or control intervention group and participate in nine interventional visits with additional pre- and post-intervention assessments. Performance in the letter updating task after training and anodal tDCS compared to sham stimulation will be analyzed as primary outcome. Further, performance on the second training task and transfer tasks will be investigated. Two follow-up visits (at 1 and 7 months post-training) will be performed to assess possible maintenance effects. Structural and functional magnetic resonance imaging (MRI) will be applied before the intervention and at the 7-month follow-up to identify possible neural predictors for successful intervention.

Significance

With this trial, we aim to provide evidence for tDCS-induced improvements of multi-session cognitive training in participants with SCD and MCI. An improved understanding of tDCS effects on cognitive training performance and neural predictors may help to develop novel approaches to counteract cognitive decline in participants with prodromal AD.

Trial registration

ClinicalTrials.gov, NCT04265378. Registered on 07 February 2020. Retrospectively registered.

Protocol version: Based on BB 004/18 version 1.2 (May 17, 2019).

Sponsor: University Medicine Greifswald.
Differences in [18F]FDG uptake in BAT of UCP1 −/− and UCP1 +/+ during adrenergic stimulation of non-shivering thermogenesis
Authors: McHugh Christian T. , Garside John , Barkes Jared , Frank Jonathan , Dragicevich Constance , Yuan Hong , Branca Rosa T.
Published: November 2020

Background

Brown adipose tissue (BAT) is a fat tissue found in most mammals that helps regulate energy balance and core body temperature through a sympathetic process known as non-shivering thermogenesis. BAT activity is commonly detected and quantified in [18F]FDG positron emission tomography/computed tomography (PET/CT) scans, and radiotracer uptake in BAT during adrenergic stimulation is often used as a surrogate measure for identifying thermogenic activity in the tissue. BAT thermogenesis is believed to be contingent upon the expression of the protein UCP1, but conflicting results have been reported in the literature concerning [18F]FDG uptake within BAT of mice with and without UCP1. Differences in animal handling techniques such as feeding status, type of anesthetic, type of BAT stimulation, and estrogen levels were identified as possible confounding variables for [18F]FDG uptake. In this study, we aimed to assess differences in BAT [18F]FDG uptake between wild-type and UCP1-knockout mice using a protocol that minimizes possible variations in BAT stimulation caused by different stress responses to mouse handling.

Results

[18F]FDG PET/CT scans were run on mice that were anesthetized with pentobarbital after stimulation of non-shivering thermogenesis by norepinephrine. While in wild-type mice [18F]FDG uptake in BAT increased significantly with norepinephrine stimulation of BAT, there was no consistent change in [18F]FDG uptake in BAT of mice lacking UCP1.

Conclusions

[18F]FDG uptake within adrenergically stimulated BAT of wild-type and UCP1-knockout mice can significantly vary such that an [18F]FDG uptake threshold cannot be used to differentiate wild-type from UCP1-knockout mice. However, while an increase in BAT [18F]FDG uptake during adrenergic stimulation is consistently observed in wild-type mice, in UCP1-knockout mice [18F]FDG uptake in BAT seems to be independent of β3-adrenergic stimulation of non-shivering thermogenesis.