bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian neural networks with variable selection for prediction of genotypic values
Authors: van Bergen Giel H. H. , Duenk Pascal , Albers Cornelis A. , Bijma Piter , Calus Mario P. L. , Wientjes Yvonne C. J. , Kappen Hilbert J.
Published: May 2020

Background

Estimating the genetic component of a complex phenotype is a complicated problem, mainly because there are many allele effects to estimate from a limited number of phenotypes. In spite of this difficulty, linear methods with variable selection have been able to give good predictions of additive effects of individuals. However, prediction of non-additive genetic effects is challenging with the usual prediction methods. In machine learning, non-additive relations between inputs can be modeled with neural networks. We developed a novel method (NetSparse) that uses Bayesian neural networks with variable selection for the prediction of genotypic values of individuals, including non-additive genetic effects.

Results

We simulated several populations with different phenotypic models and compared NetSparse to genomic best linear unbiased prediction (GBLUP), BayesB, their dominance variants, and an additive by additive method. We found that when the number of QTL was relatively small (10 or 100), NetSparse had 2 to 28 percentage points higher accuracy than the reference methods. For scenarios that included dominance or epistatic effects, NetSparse had 0.0 to 3.9 percentage points higher accuracy for predicting phenotypes than the reference methods, except in scenarios with extreme overdominance, for which reference methods that explicitly model dominance had 6 percentage points higher accuracy than NetSparse.

Conclusions

Bayesian neural networks with variable selection are promising for prediction of the genetic component of complex traits in animal breeding, and their performance is robust across different genetic models. However, their large computational costs can hinder their use in practice.
CSN: unsupervised approach for inferring biological networks based on the genome alone
Authors: Galili Maya , Tuller Tamir
Published: May 2020

Background

Most organisms cannot be cultivated, as they live in unique ecological conditions that cannot be mimicked in the lab. Understanding the functionality of those organisms’ genes and their interactions by performing large-scale measurements of transcription levels, protein-protein interactions or metabolism, is extremely difficult and, in some cases, impossible. Thus, efficient algorithms for deciphering genome functionality based only on the genomic sequences with no other experimental measurements are needed.

Results

In this study, we describe a novel algorithm that infers gene networks that we name Common Substring Network (CSN). The algorithm enables inferring novel regulatory relations among genes based only on the genomic sequence of a given organism and partial homolog/ortholog-based functional annotation. It can specifically infer the functional annotation of genes with unknown homology.

This approach is based on the assumption that related genes, not necessarily homologs, tend to share sub-sequences, which may be related to common regulatory mechanisms, similar functionality of encoded proteins, common evolutionary history, and more.

We demonstrate that CSNs, which are based onS. cerevisiaeandE. coligenomes, have properties similar to ‘traditional’ biological networks inferred from experiments. Highly expressed genes tend to have higher degree nodes in the CSN, genes with similar protein functionality tend to be closer, and the CSN graph exhibits a power-law degree distribution. Also, we show how the CSN can be used for predicting gene interactions and functions.

Conclusions

The reported results suggest that ‘silent’ code inside the transcript can help to predict central features of biological networks and gene function. This approach can help researchers to understand the genome of novel microorganisms, analyze metagenomic data, and can help to decipher new gene functions.

Availability

Our MATLAB implementation of CSN is available athttps://www.cs.tau.ac.il/~tamirtul/CSN-Autogen
Developing model biobanking consent language: what matters to prospective participants?
Authors: Beskow Laura M. , Hammack-Aviran Catherine M. , Brelsford Kathleen M.
Published: May 2020

Background

Efforts to improve informed consent have led to calls for providing information a reasonable person would want to have, in a way that facilitates understanding of the reasons why one might or might not want to participate. At the same time, advances in large-scale genomic research have expanded both the opportunities and the risks for participants, families, and communities. To advance the use of effective consent materials that reflect this landscape, we used empirical data to develop model consent language, as well as brief questions to assist people in thinking about their own values relative to participation.

Methods

We conducted in-person interviews to gather preliminary input on these materials from a diverse sample (n = 32) of the general population in Nashville, Tennessee. We asked them to highlight information they found especially reassuring or concerning, their hypothetical willingness to participate, and their opinions about the values questions.

Results

Consent information most often highlighted as reassuring included the purpose of the biobank, the existence and composition of a multidisciplinary oversight committee, the importance of participants’ privacy and efforts to protect it, and controlled access to a scientific database. Information most often highlighted as concerning included the deposition of data in a publicly accessible database, the risk of unintended access to data, the potential for non-research use of data, and use of medical record information in general. Seventy-five percent of participants indicated initial willingness to participate in the hypothetical biobank; this decreased to 66% as participants more closely considered the information over the course of the interview. A large majority rated the values questions as helpful.

Conclusions

These results are consistent with other research on public perspectives on biobanking and genomic cohort studies, suggesting that our model language effectively captures commonly expressed reasons for and against participation. Our study enriches this literature by connecting specific consent form disclosures with qualitative data regarding what participants found especially reassuring or concerning and why. Interventions that facilitate individuals’ closer engagement with consent information may result in participation decisions more closely aligned with their values.
Blackfly fever and dermatitis caused by Simulium kiritshenkoi: a human case report in Iran
Authors: Tabatabaei Farbod , Azarmi Sahar , Abbaszadeh Afshar Mohammad Javad , Yarizadeh Hamed , Mohtasebi Sina
Published: May 2020

Background

Besides the considerable role of blackflies to the transmission of many disease agents, these flies considered as annoying biting pests of wildlife, livestock, poultry, and humans. There are few literature reports of blackfly fever following Simulium spp. This study describes a case of blackfly fever and dermatitis following blackflies numerous bites in Iran.

Case presentation

The present report describes a 25-year-old man that was attacked by numerous flies while fishing and camping near Namrood river in Firuzkuh County, Tehran Province, Iran. Pruritic dermatitis with marked edema appeared mainly on the hands and legs and subsequently, the patient’s condition worsened with swollen lymph nodes, joints aching, and 40 °C fever. The patient’s clinical signs and symptoms were alleviated by injection of intramuscular Dexamethasone Phosphate (DEXADIC®) 8 mg/2 ml after 24 h.

Conclusions

This study reported a human case with blackfly fever and dermatitis following numerous bites of Simulium kiritshenkoi, for the first time in Iran.
Epidemiological analysis of the Kaohsiung city strategy for dengue fever quarantine and epidemic prevention
Authors: Pan Chao-Ying , Liu Wei-Liang , Su Matthew-P. , Chang Te-Pin , Ho Hui-Pin , Shu Pei-Yun , Huang Joh-Jong , Lin Li-Jen , Chen Chun-Hong
Published: May 2020

Background

Dengue is endemic in over 100 countries and is an important public health problem worldwide. Dengue fever is not endemic in Taiwan; the importation of dengue viruses from neighboring countries via close commercial links and air travel is considered to be the cause of local outbreaks. Therefore, efforts toward disease control have focused on preventing the importation of dengue into Taiwan. In this study, we investigated the relationships between the numbers of imported and indigenous dengue cases to test the validity of this strategy.

Methods

Data on cases of dengue fever that occurred between 2013 and 2018 were obtained from the surveillance systems of the Taiwan Center for Disease Control and Kaohsiung City Health Department. Standard epidemiological data, including the monthly numbers of indigenous and imported cases of dengue, were calculated. Potential associations between the numbers of indigenous and imported cases were investigated using correlation analyses.

Results

We identified a possible relationship between the period of disease concealment and the number of imported dengue cases, which resulted in epidemics of indigenous dengue fever within local communities. Further analysis of confirmed cases during previous epidemics in Kaohsiung City found that the risk of indigenous dengue fever may be related to the likelihood that patients with imported dengue fever will stay within local communities.

Conclusion

Given the correlations found between imported and indigenous cases of dengue fever, as well as the relationship between the disease concealment period and the risk of indigenous dengue fever, prevention of disease importation and efficient identification of dengue cases within high-risk communities remain the major priorities for disease control.
Clinical and ultrasonographic features of medullary thyroid microcarcinomas compared with papillary thyroid microcarcinomas: a retrospective analysis
Authors: Li Xiaoyu , Zhou Wei , Zhan Weiwei
Published: May 2020

Background

To identify the sonographic features that help to differentiate medullary thyroid microcarcinomas (MTMCs) from papillary thyroid microcarcinomas (PTMCs).

Methods

A total of 46 MTMCs in 41 patients and 136 PTMCs in 104 patients that were proven by surgery and pathology were included in the study. Patient age and nodule size were analyzed by independent sample t-tests, and sex, multiplicity and cervical lymph node metastases were analyzed by χ2 or Fisher’s exact tests. Univariate analysis and multivariate logistic regression analysis were performed on the sonographic features of thyroid nodules, including location, shape, boundary, margin, peripheral halo ring, echogenicity, composition, calcifications and vascularization.

Results

Compared with the corresponding number of patients with PTMCs, more MTMC patients had cervical lymph node metastases (P = 0.040). There were no significant differences in age, sex, nodule size, multiplicity, location, boundary, margin, peripheral halo ring, echogenicity or microcalcifications between MTMCs and PTMCs (P > 0.05 for all). However, significant differences were found in shape (P = 0.000), composition (P = 0.032), macrocalcifications (P = 0.004) and vascularity (P = 0.000) between the two groups.

Conclusions

There were some overlapping sonographic features between MTMCs and PTMCs. However, MTMCs tended to have a > 50% solid composition, be ovoid to round nodules with macrocalcifications and be hypervascular. Cervical lymph node metastases were more common in MTMC patients.
HTRA1 rs11200638 variant and AMD risk from a comprehensive analysis about 15,316 subjects
Authors: Liu Ying , Jin Huipeng , Wei Dong , Li Wenxiu
Published: May 2020

Background

The high-temperature requirement factor A1 (HTRA1) gene located at 10q26 locus has been associated with age-related macular degenerative (AMD), with the significantly related polymorphism being (rs11200638, −625G/A), however, above association is not consistent. We investigated a comprehensive analysis to evaluate the correlations between rs11200638 polymorphism and AMD susceptibility thoroughly addressing this issue.

Methods

An identification was covered from the PubMed and Wanfang databases until 27th Jan, 2020. Odds ratios (OR) with 95% confidence intervals (CI) were applied to evaluate the associations. After a thorough and meticulous search, 35 different articles (33 case-control studies with HWE, 22 case-control studies about wet/dry AMD) were retrieved.

Results

Individuals carrying A-allele or AA genotype may have an increased risk to be AMD disease. For example, there has a significantly increased relationship between rs11200638 polymorphism and AMD both for Asians (OR: 2.51, 95%CI: 2.22–2.83 for allelic contrast) and Caucasians [OR (95%CI) = 2.63(2.29–3.02) for allelic contrast]. Moreover, a similar trend in the source of control was detected. To classify the type of AMD, increased association was also observed in both wet (OR: 3.40, 95%CI: 2.90–3.99 for dominant model) and dry (OR: 2.08, 95%CI: 1.24–3.48 for dominant model) AMD. Finally, based on the different genotyping methods, increased relationships were identified by sequencing, TaqMan, PCR-RFLP and RT-PCR.

Conclusions

Our meta-analysis demonstrated that HTRA1 rs11200638 polymorphism may be related to the AMD development, especially about individuals carrying A-allele or AA genotype, who may be as identified targets to detect and intervene in advance. Further studies using Larger sample size studies, including information about gene-environment interactions will be necessary to carry out.
Correction to: SMART coils for intracranial aneurysm repair - a single center experience
Authors: Behme Daniel , Sack Henrik , Tsogkas Ioannis , Rohde Veit , Psychogios Marios-Nikos
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Magnitude and predictors of common mental disorder among people with HIV/AIDS in Ethiopia: a systematic review and meta-analysis
Authors: Belayneh Zelalem , Mekuriaw Birhanie , Mehare Tsegaye , Shumye Seid , Tsehay Mekonnen
Published: May 2020

Background

Common mental disorders are frequent psychiatric comorbid conditions among people with HIV/AIDS. The presence of such psychiatric disorders negatively affects the treatment adherence, viral load suppression, quality of life, treatment outcomes and functionality of people with HIV/AIDS. However, available studies in Ethiopia have a great variation and inconsistency of reported results have been observed regarding the magnitude and associated factors of common mental disorder. Thus, conducting a systematic review and meta-analysis of existing literatures can have a paramount importance to show its summarized figure.

Methods

Literatures search was performed using databases (PubMed/Medline, Science Direct and PsycINFO. Grey literatures were also searched from Google and Google Scholar. Data were extracted from primary studies using a data extraction format prepared in Microsoft Excel and exported to STATA-version 14 statistical software for analysis. The I2 test was used to assess the heterogeneity of primary articles. The result of the test showed that there was heterogeneity between primary studies. This leads us to execute a random effect meta-analysis to estimate the pooled prevalence of common mental disorder with corresponding 95% confidence interval.

Results

A total of 13 primary studies comply with the inclusion criteria were included in this systematic review. The pooled prevalence of common mental disorder was found to be 28.83% (95% CI: 17.93, 39.73) among people with HIV/AIDS in Ethiopia. The highest prevalence of common mental disorder (35.20%) was observed among studies in which Kessler-10 was used as a screening tool. Single marital status (OR = 1.83; 95%CI: 1.03, 3.27), HIV/AIDS-related stigma (OR = 2.21; 95%CI: 1.68, 2.90) and current job unavailability (OR = 1.38; 95%CI: 1.01, 1.88) had statistically significant association with common mental disorder.

Conclusion

The result of this review showed that nearly one among three individuals with HIV/AIDS is suffering from common mental disorder in Ethiopia. This calls a need to integrate the mental health and psycho-social support into the HIV/AIDS care.

Trial registration

PROSPERO- CRD42019132402. Registered on 05/08/2019.
Factors influencing cognitive reactivity among young adults at high risk for depression in China: a cross-sectional study
Authors: Huang Fei Fei , Wen Zhi Peng , Li Qi , Chen Bin , Weng Wen Jie
Published: May 2020

Background

Understanding the factors influencing cognitive reactivity (CR) may help identify individuals at risk for first episode depression and relapse and facilitate routine access to preventative treatments. However, few studies have examined the relationship between CR and depression in Asian countries. This study was performed to assess the current status of CR among Chinese young adults and explore influencing factors.

Methods

A national cross-sectional online study using convenience sampling was conducted among 1597 healthy young adults in China (response rate: 93.94%) with a mean age of 24.34 (SD = 5.76) years.

Results

The mean CR score was 51.36 ± 18.97 (range 0–130). Binary logistic regression showed that a low level of CR was associated with the following factors: high self-compassion, high social support, high resilience, high monthly household income, and living in a rural area, with odds ratios (ORs) ranging from 0.14 to 0.70. Young adults in full-time employment, experiencing poor sleep, with high neuroticism, who reported frequent sad mood, and who had a high intensity of negative life events had increased CR to depression, with ORs ranging from 1.18 to 6.66. The prediction probability of these factors was 75.40%. Causal relationships among the influencing factors and CR could not be explored.

Conclusions

The self-reported CR levels among Chinese young adults were moderate. Enhancing self-compassion, resilience, and social support for young adults and reducing negative life events, neuroticism, and poor sleep may help decrease CR. These findings may help healthcare providers or researchers determine how to cultivate and improve the CR of young adults by establishing documented policies and/or improving intervention efficacies.
Implementation and adoption of a health insurance support tool in the electronic health record: a mixed methods analysis within a randomized trial
Authors: Hatch Brigit , Tillotson Carrie , Huguet Nathalie , Marino Miguel , Baron Andrea , Nelson Joan , Sumic Aleksandra , Cohen Deborah , E. DeVoe Jennifer
Published: May 2020

Background

In addition to delivering vital health care to millions of patients in the United States, community health centers (CHCs) provide needed health insurance outreach and enrollment support to their communities. We developed a health insurance enrollment tracking tool integrated within the electronic health record (EHR) and conducted a hybrid implementation-effectiveness trial in a CHC-based research network to assess tool adoption using two implementation strategies.

Methods

CHCs were recruited from the OCHIN practice-based research network. Seven health center systems (23 CHC clinic sites) were recruited and randomized to receive basic educational materials alone (Arm 1), or these materials plus facilitation (Arm 2) during the 18-month study period, September 2016–April 2018. Facilitation consisted of monthly contacts with clinic staff and utilized audit and feedback and guided improvement cycles. We measured total and monthly tool utilization from the EHR. We conducted structured interviews of CHC staff to assess factors associated with tool utilization. Qualitative data were analyzed using an immersion-crystallization approach with barriers and facilitators identified using the Consolidated Framework for Implementation Research.

Results

The majority of CHCs in both study arms adopted the enrollment tool. The rate of tool utilization was, on average, higher in Arm 2 compared to Arm 1 (20.0% versus 4.7%, p < 0.01). However, by the end of the study period, the rate of tool utilization was similar in both arms; and observed between-arm differences in tool utilization were largely driven by a single, large health center in Arm 2. Perceived relative advantage of the tool was the key factor identified by clinic staff as driving tool utilization. Implementation climate and leadership engagement were also associated with tool utilization.

Conclusions

Using basic education materials and low-intensity facilitation, CHCs quickly adopted an EHR-based tool to support critical outreach and enrollment activities aimed at improving access to health insurance in their communities. Though facilitation carried some benefit, a CHC’s perceived relative advantage of the tool was the primary driver of decisions to implement the tool.

Trial registration

ClinicalTrials.gov: NCT02355262, Posted February 4, 2015.
Medical infrared thermal imaging of syringomyelia in the Cavalier King Charles Spaniel
Authors: Larkin M. , Loughin C. , Marino D. , Dewey C. , Umbaugh S. , Sackman J.
Published: May 2020

Background

Medical infrared thermal imaging (MITI) is a non-invasive imaging modality gaining popularity in the veterinary field. An infrared camera captures emission of heat and creates a color map in the form of a thermogram. Topical heat emission is influenced by localized disease processes as a result of autonomic nervous system imbalance. The purpose of this study was to determine the utility of using thermography to identify changes in thermographic patterns associated with syringomyelia (SM) presence or absence in Cavalier King Charles Spaniels (CKCS) with Chiari-like Malformation (CLM).

Results

In CKCS with CLM, MITI was most accurate at a texture distance of 6. Optimizing imaging feature sets produced a highest accuracy of 69.9% (95% CI: 59.5–79.0%), with 81.3% sensitivity and 57.8% specificity for identifying the presence of syringomyelia.

Conclusion

Thermographic image analysis is a successful non-invasive, diagnostic test that can be used to screen for syringomyelia presence in a CKCS with CLM.
Empagliflozin prevents doxorubicin-induced myocardial dysfunction
Authors: Sabatino Jolanda , De Rosa Salvatore , Tammè Laura , Iaconetti Claudio , Sorrentino Sabato , Polimeni Alberto , Mignogna Chiara , Amorosi Andrea , Spaccarotella Carmen , Yasuda Masakazu , Indolfi Ciro
Published: May 2020

Background

Empagliflozin showed efficacy in controlling glycaemia, leading to reductions in HbA1c levels, weight loss and blood pressure, compared to standard treatment. Moreover, the EMPA-REG OUTCOME trial demonstrated a 14% reduction of major adverse cardiovascular events (MACE), a 38% reduction in cardiovascular (CV) death and a 35% reduction in the hospitalization rate for heart failure (HF). These beneficial effect on HF were apparently independent from glucose control. However, no mechanistic in vivo studies are available to explain these results, yet. We aimed to determine the effect of empagliflozin on left ventricular (LV) function in a mouse model of doxorubicin-induced cardiomyopathy (DOX-HF).

Methods

Male C57Bl/6 mice were randomly assigned to the following groups: controls (CTRL, n = 7), doxorubicin (DOX, n = 14), DOX plus empagliflozin (DOX + EMPA, n = 14), or DOX plus furosemide (DOX + FURO group, n = 7). DOX was injected intraperitoneally. LV function was evaluated at baseline and after 6 weeks of treatment using high-resolution echocardiography with 2D speckle tracking (Vevo 2100). Histological assessment was obtained using Haematoxylin and Eosin and Masson’s Goldner staining.

Results

A significant decrease in both systolic and diastolic LV function was observed after 6 weeks of treatment with doxorubicin. EF dropped by 32% (p = 0.002), while the LS was reduced by 42% (p < 0.001) and the CS by 50% (p < 0.001). However, LV function was significantly better in the DOX + EMPA group, both in terms of EF (61.30 ± 11% vs. 49.24 ± 8%, p = 0.007), LS (− 17.52 ± 3% vs. − 13.93 ± 5%, p = 0.04) and CS (− 25.75 ± 6% vs. − 15.91 ± 6%, p < 0.001). Those results were not duplicated in the DOX + FURO group. Hearts from the DOX + EMPA group showed a 50% lower degree of myocardial fibrosis, compared to DOX mice (p = 0.03). No significant differences were found between the DOX + FURO and the DOX group (p = 0.103).

Conclusion

Empagliflozin attenuates the cardiotoxic effects exerted by doxorubicin on LV function and remodelling in nondiabetic mice, independently of glycaemic control. These findings support the design of clinical studies to assess their relevance in a clinical setting.
N-alkylisatin-based microtubule destabilizers bind to the colchicine site on tubulin and retain efficacy in drug resistant acute lymphoblastic leukemia cell lines with less in vitro neurotoxicity
Authors: Keenan Bryce , Finol-Urdaneta Rocio K. , Hope Ashleigh , Bremner John B. , Kavallaris Maria , Lucena-Agell Daniel , Oliva María Ángela , Díaz Jose Fernando , Vine Kara L.
Published: May 2020

Background

Drug resistance and chemotherapy-induced peripheral neuropathy continue to be significant problems in the successful treatment of acute lymphoblastic leukemia (ALL). 5,7-Dibromo-N-alkylisatins, a class of potent microtubule destabilizers, are a promising alternative to traditionally used antimitotics with previous demonstrated efficacy against solid tumours in vivo and ability to overcome P-glycoprotein (P-gp) mediated drug resistance in lymphoma and sarcoma cell lines in vitro. In this study, three di-brominated N-alkylisatins were assessed for their ability to retain potency in vincristine (VCR) and 2-methoxyestradiol (2ME2) resistant ALL cell lines. For the first time, in vitro neurotoxicity was also investigated in order to establish their suitability as candidate drugs for future use in ALL treatment.

Methods

Vincristine resistant (CEM-VCR R) and 2-methoxyestradiol resistant (CEM/2ME2-28.8R) ALL cell lines were used to investigate the ability of N-alkylisatins to overcome chemoresistance. Interaction of N-alkylisatins with tubulin at the the colchicine-binding site was studied by competitive assay using the fluorescent colchicine analogue MTC. Human neuroblastoma SH-SY5Y cells differentiated into a morphological and functional dopaminergic-like neurotransmitter phenotype were used for neurotoxicity and neurofunctional assays. Two-way ANOVA followed by a Tukey’s post hoc test or a two-tailed paired t test was used to determine statistical significance.

Results

CEM-VCR R and CEM/2ME2-28.8R cells displayed resistance indices of > 100 to VCR and 2-ME2, respectively. CEM-VCR R cells additionally displayed a multi-drug resistant phenotype with significant cross resistance to vinblastine, 2ME2, colchicine and paclitaxel consistent with P-gp overexpression. Despite differences in resistance mechanisms observed between the two cell lines, the N-alkylisatins displayed bioequivalent dose-dependent cytotoxicity to that of the parental control cell line. The N-alkylisatins proved to be significantly less neurotoxic towards differentiated SH-SY5Y cells than VCR and vinblastine, evidenced by increased neurite length and number of neurite branch points. Neuronal cells treated with 5,7-dibromo-N-(p-hydroxymethylbenzyl)isatin showed significantly higher voltage-gated sodium channel function than those treated with Vinca alkaloids, strongly supportive of continued action potential firing.

Conclusions

The N-alkylisatins are able to retain cytotoxicity towards ALL cell lines with functionally distinct drug resistance mechanisms and show potential for reduced neurotoxicity. As such they pose as promising candidates for future implementation into anticancer regimes for ALL. Further in vivo studies are therefore warranted.
“Pairing assistance”: the effective way to solve the breakdown of health services system caused by COVID-19 pandemic
Authors: Chen Tianxiang , Wang Ying , Hua Lei
Published: May 2020

The most terrifying thing about pandemic could be the large number of patients running against the health service system, which causes a serious shortage of health resources, especially medical personnel. Plotting mortality and diagnosis rates against medical staff resources in 16 cities in Hubei Province, where the epidemic was initially concerned and the most severe, shows a significant negative correlation, indicating the critical role of medical staff resources in controlling epidemics. Nevertheless, it is difficult to ensure that there exist enough medical personnel in cities severely hit by the outbreak. China provides solutions by adopting nationwide “pairing assistance” measures with at least one province assisting one city to alleviate pressure in the most severe area. By plotting the number of patients receiving treatment against day, it is clear that implementing “pairing assistance” is a turning point in China’s fight against epidemics.
Hyperlipidemias in elderly patients: results from the Berlin Aging Study II (BASEII), a cross-sectional study
Authors: Rosada Adrian , Kassner Ursula , Weidemann Felix , König Maximilian , Buchmann Nikolaus , Steinhagen-Thiessen Elisabeth , Spira Dominik
Published: May 2020

Background

Hyperlipidemias are common and the last decades have seen substantially growing evidence of their causative role in the development of atherosclerosis and subsequent cardiovascular diseases. Since hyperlipidemias usually do not cause direct clinical symptoms, they often remain undiagnosed until a serious cardiovascular event occurs. Especially for LDL-hypercholesteremia, there are well-established treatment options available to prevent the occurrence of atherosclerosis. However, there is a lack of knowledge regarding the proper treatment of elderly patients. The goal of this study was to assess the prevalence of hyperlipidemia in a group of young and a group of elderly community-dwelling participants and to determine to what extent treatment of hyperlipidemia should be initiated or required.

Methods

Crossectional data from a total of 2151 subjects (1657 in the elderly group, mean age 69, and 494 in the young group (control group), mean age 29) of the Berlin Aging Study II (BASE-II) were available. Medical history was assessed and recorded by trained physicians and prevalence of lipid disorders was determined with laboratory tests, including a lipid-profile.

Results

A large proportion of subjects (39%) were unaware of an existing lipid disorder. The prevalence of hyperlipidemia was more frequent in the elderly group (76%) compared to the young group (41%). Hypercholesterolemia was the most common diagnosed disorder (64%), followed by hyperlipoproteinemia(a) (18%), hypertriglyceridemia (7%) and combined hyperlipoproteinaemia (5%). Only a minority of this cohort was treated with lipid-lowering medication (17%) and of those treatment targets according to ESC guidelines were reached only in 16.5 %.

Conclusions

Hyperlipidemias appear underdiagnosed and undertreated. As the prevalence of these disorders increases with age and with regard to their role as a major modifiable risk factor for cardiovascular disease it seems to be advisable to aim for more consistent and sustainable screening and treatment of these common disorders.

Trial Registration

BASE-II registered with the clinical trial registry Deutsches Register Klinischer Studien (DRKS00009277).
Real-time surveillance of surgical margins via ICG-based near-infrared fluorescence imaging in patients with OSCC
Authors: Pan Jiongru , Deng Han , Hu Shiqi , Xia Chengwan , Chen Yongfeng , Wang Jianquan , Wang Yuxin
Published: May 2020

Background

Local recurrence is the main cause of death among patients with oral squamous cell carcinoma (OSCC). This study assessed near-infrared fluorescence (NIF) imaging and spectroscopy to monitor surgical margins intraoperatively for OSCC.

Methods

Cytological and animal experiments were first performed to confirm the feasibility of monitoring surgical margins with NIF imaging and spectroscopy. Then, 20 patients with OSCC were included in the clinical trials. At 6–8 h after 0.75 mg/kg indocyanine green (ICG) injection, all patients underwent surgery with NIF imaging. During the surgery, both NIF images and quantified fluorescence intensity were acquired to monitor the surgical margins.

Results

In cytological and animal experiments, the results showed it was feasible to monitor surgical margins with NIF imaging and spectroscopy. Fluorescence was detected in primary tumors in all patients. The fluorescence intensities of the tumor, peritumoral, and normal tissues were 398.863 ± 151.47, 278.52 ± 84.89, and 274.5 ± 100.93 arbitrary units (AUs), respectively (P < 0.05). The SBR of tumor to peritumoral tissue and normal tissues was computed to be 1.45 ± 0.36 and 1.56 ± 0.41, respectively. After primary tumor excision, the wounds showed abnormal fluorescence in four patients (4/20), and residual cancer cells were confirmed by pathological examination in two patients (2/20).

Conclusion

These findings confirmed the complementary value of NIF imaging during radical tumor resection of OSCC. Before tumor resection, we could utilize the fluorescence margin produced by ICG NIF imaging to determine the surgical margin. Moreover, after tumor blocks were removed, the status of surgical margin could also be evaluated rapidly by ICG NIF imaging of tumor bed and in vitro specimens.
COVID-19 in Africa: care and protection for frontline healthcare workers
Authors: Chersich Matthew F. , Gray Glenda , Fairlie Lee , Eichbaum Quentin , Mayhew Susannah , Allwood Brian , English Rene , Scorgie Fiona , Luchters Stanley , Simpson Greg , Haghighi Marjan Mosalman , Pham Minh Duc , Rees Helen
Published: May 2020

Medical staff caring for COVID-19 patients face mental stress, physical exhaustion, separation from families, stigma, and the pain of losing patients and colleagues. Many of them have acquired SARS-CoV-2 and some have died. In Africa, where the pandemic is escalating, there are major gaps in response capacity, especially in human resources and protective equipment. We examine these challenges and propose interventions to protect healthcare workers on the continent, drawing on articles identified on Medline (Pubmed) in a search on 24 March 2020. Global jostling means that supplies of personal protective equipment are limited in Africa. Even low-cost interventions such as facemasks for patients with a cough and water supplies for handwashing may be challenging, as is ‘physical distancing’ in overcrowded primary health care clinics. Without adequate protection, COVID-19 mortality may be high among healthcare workers and their family in Africa given limited critical care beds and difficulties in transporting ill healthcare workers from rural to urban care centres. Much can be done to protect healthcare workers, however. The continent has learnt invaluable lessons from Ebola and HIV control. HIV counselors and community healthcare workers are key resources, and could promote social distancing and related interventions, dispel myths, support healthcare workers, perform symptom screening and trace contacts. Staff motivation and retention may be enhanced through carefully managed risk ‘allowances’ or compensation. International support with personnel and protective equipment, especially from China, could turn the pandemic’s trajectory in Africa around. Telemedicine holds promise as it rationalises human resources and reduces patient contact and thus infection risks. Importantly, healthcare workers, using their authoritative voice, can promote effective COVID-19 policies and prioritization of their safety. Prioritizing healthcare workers for SARS-CoV-2 testing, hospital beds and targeted research, as well as ensuring that public figures and the population acknowledge the commitment of healthcare workers may help to maintain morale. Clearly there are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic’s potentially devastating heath, socio-economic and security impacts on the continent.
Radiation induced temporal lobe necrosis in nasopharyngeal cancer patients after radical external beam radiotherapy
Authors: Wu Vincent W. C. , Tam Shing-yau
Published: May 2020

Radiation-induced temporal lobe necrosis (TLN) is one of the late post-radiotherapy complications in nasopharyngeal cancer (NPC) patients. Since NPC is common to have skull base infiltration, irradiation of the temporal lobes is inevitable despite the use of the more advanced intensity-modulated radiotherapy (IMRT). Moreover, the diagnosis and treatment of TLN remain challenging. In this review, we discuss the diagnosis of TLN with conventional and advanced imaging modalities, onset and predictive parameters of TLN development, the impact of IMRT on TLN in terms of incidence and dosimetric analyzes, and the recent advancements in the treatment of TLN.
Identification of risk factors for acute kidney injury after pulmonary endarterectomy with cardiopulmonary bypass
Authors: Dong Peng , Xue Fu-Shan , Liu Shao-Hua
Published: May 2020

The letter to the editor made several comments on possible issues in the recent article by Zhang et al. determining the risk factors of acute kidney injury after pulmonary endarterectomy with cardiopulmonary bypass, which has been published in Journal of Cardiothoracic Surgery at December 30, 2019.
Independent risk factors and the long-term outcomes for postoperative continuous renal replacement treatment in patients who underwent emergency surgery for type a acute aortic dissection
Authors: Wang Zhigang , Ge Min , Chen Tao , Chen Cheng , Zong Qiuyan , Lu Lichong , Wang Dongjin
Published: May 2020

Objective

The study objective was to investigate the incidence and risk factors of continuous renal replacement therapy (CRRT) in patients undergoing emergency surgery for type A acute aortic dissection (TA-AAD) and evaluate the perioperative and long-term outcomes.

Methods

From January 2014 to December 2018, 712 consecutive patients were enrolled in the study. These patients were divided into two groups according to whether or not needed postoperative CRRT: the CRRT group vs the control group. Univariate analysis and binary logistic regression analysis were used to analyze the risk factors of CRRT. To avoid the selection bias and confounders, baseline characteristics were matched for propensity scores. Kaplan-Meier curves were generated to provide survival estimates at postoperative points in time.

Results

Before propensity score matching, univariate analysis showed that there were significant differences in age, preoperative hypertension, pericardial effusion, preoperative serum creatinine (sCr), intraoperative need for combined coronary artery bypass grafting (CABG) or mitral valve or tricuspid valve surgery, cardiopulmonary bypass (CPB) time, extracorporeal circulation assistant time, aortic cross-clamp time, drainage volume 24 h after surgery and ventilator time between two groups. All were higher in the CRRT group (P < 0.05). These risk factors were included in binary logistic regression. It showed that preoperative sCr and CPB time were independent risk factors for CRRT patients undergoing surgery for TA-AAD. And there were significant differences regarding 30-day mortality (P < 0.001) and long-term overall cumulative survival (P < 0.001) with up to a 6-year follow-up. After propensity scoring, 29 pairs (58 patients) were successfully matched. Among these patients, the analysis showed that CPB time was still significantly longer in the CRRT group (P = 0.004), and the 30-day mortality rate was also higher in this group (44.8% vs 10.3%; P = 0.003).

Conclusion

CRRT after TA-AAD is common and worsened short- and long- term mortality. The preoperative sCr and CPB time are independent risk factors for postoperative CRRT patients. Shorten the CPB time as much as possible is recommended to reduce the risk of CRRT after the operation.
Phenotypes and outcomes in middle‐aged patients with diabetic foot ulcers: a retrospective cohort study
Authors: Tong Tao , Yang Cailian , Tian Wenqing , Liu Zhiping , Liu Bo , Cheng Jun , Cheng Qingfeng , Zhou Bo
Published: May 2020

Background

Although ageing could increase the risk of delayed healing in diabetic foot ulcers (DFUs) patients, data from middle‐aged patients remains greatly limited. The purpose of this study was to explore the clinical phenotypes, outcomes and predictive factors of DFU in middle‐aged patients.

Methods

A retrospective cohort study conducted with 422 consecutive inpatients with DFUs who visited our hospital between May 2010 and September 2017; participants were recruited and assigned according to age to either the middle‐aged group or the elderly group. The Demographics, ulcer characteristics, comorbidities and diabetes complications, laboratory tests, socioeconomic data and final outcomes were collected. Moreover, predictive factors of adverse outcomes in middle‐aged DFUs patients were assessed.

Results

Middle‐aged patients were more likely to have worse lifestyle and glucose control, were more likely to have microangiopathy as a complication, and tended to have larger and deeper ulcers; however, these patients also had higher rates of healing and lower rates of mortality and major amputaion than elderly patients. Severe infection, living alone, current smoking cigarettes, and having a high white blood cell count were independent risk factors for adverse outcomes in middle‐aged patients.

Conclusions

DFUs are relatively common in middle‐aged patients with diabetes, and these patients have unique clinical phenotypes and risk profiles. Nonetheless, further investigation is needed to clarify whether intervention targeting these easily recognizable risk factors can improve healing and survival rates in middle‐aged DFU patients.
LncRNA TONSL-AS1 regulates miR-490-3p/CDK1 to affect ovarian epithelial carcinoma cell proliferation
Authors: Liu Yan , Li Ling , Wang Xiangyang , Wang Ping , Wang Zhongxian
Published: May 2020

Background

LncRNA TONSL-AS1 has been characterized as a critical player in gastric cancer. By analyze the TCGA dataset, we observed the upregulation of TONSL-AS1 in ovarian epithelial carcinoma (EOC). We therefore investigated the involvement of TONSL-AS1 in EOC.

Methods

The differential expression of TONSL-AS1 in EOC was first explored by analyzing the TCGA dataset. The effects of overexpression of TONSL-AS1 and miR-490-3p on the expression of CDK1 mRNA and protein in OVCAR3 cells were evaluated by qPCR and western blot, respectively. CCK-8 assay was performed to investigate the effects of overexpression of TONSL-AS1, miR-490-3p and CDK1 on proliferation of OVCAR3 cells.

Results

We observed that TONSL-AS1 was upregulated in EOC tumor tissues from EOC patients, and its high expression level was correlated with poor survival. Dual luciferase assay and RNA interaction prediction showed the direct interaction between TONSL-AS1 and miR-490-3p. However, overexpression of miR-490-3p did not affect the expression of TONSL-AS1. Instead, overexpression of TONSL-AS1 resulted in the upregulation of CDK1, a target of miR-490-3p, in EOC cells. Overexpression of TONSL-AS1 and CDK1 resulted in increased proliferation rate of EOC cells. Overexpression of miR-490-3p played an opposite role and reduced the effects of overexpression of TONSL -AS1 and CDK1.

Conclusions

Therefore, TONSL-AS1 may regulate miR-490-3p/CDK1 to affect EOC cell proliferation.
Prognostic significance of baseline T cells, B cells and neutrophil-lymphocyte ratio (NLR) in recurrent ovarian cancer treated with chemotherapy
Authors: Henriksen Jon Røikjær , Nederby Line , Donskov Frede , Waldstrøm Marianne , Adimi Parvin , Jakobsen Anders , Steffensen Karina Dahl
Published: May 2020

Purpose

Biomarkers are needed to guide treatment decisions in recurrent ovarian cancer, as a high proportion of patients do not benefit from treatments. Data on immune subsets in patients receiving chemotherapy are scarce. We investigated the impact of T cells, B cells, neutrophils and the neutrophil-lymphocyte ratio (NLR) in ovarian cancer patients receiving palliative chemotherapy.

Methods

Blood samples were collected prospectively at baseline in recurrent ovarian cancer (N = 72) receiving chemotherapy. T cells, B cells, neutrophils, and NLR were analyzed. Primary and secondary endpoints were overall survival (OS) and treatment response, respectively. Cut-offs for T and B cells were predefined.

Results

In patients with low vs. high T and B cells counts, OS was 6.1 months vs 12.0 months (P = 0.017) and 6.1 months vs 12.0 months (P = 0.011, respectively. Low T and B cells analyzed as continuous variables were also associated with unfavorable OS, P = 0.011 and P = 0.007, respectively. Neutrophils had no significant prognostic impact. Median NLR was 4.1. High vs. low NLR was associated with poor survival, 7.4 months vs. 15.9 months (P = 0.012). In multivariate analysis including platinum sensitivity, number of prior lines of chemotherapy, and performance status, high NLR remained an independent poor prognostic factor HR: 2.17 (95% CI 1.21–3.88) (P = 0.009). High NLR was also significantly associated with lack of response, OR 0.15 (95% CI: 0.04–0.51) (P = 0.002).

Conclusion

In recurrent ovarian cancer patients undergoing palliative chemotherapy, low T and B lymphocyte counts had an unfavorable prognostic impact. High NLR was associated with lack of response and a poor prognosis, and the parameter may be used in patient counselling and treatment decisions.
Simultaneous targeting of HER family pro-survival signaling with Pan-HER antibody mixture is highly effective in TNBC: a preclinical trial with PDXs
Authors: Reddy Tejaswini P. , Choi Dong S. , Anselme Ann C. , Qian Wei , Chen Wen , Lantto Johan , Horak Ivan D. , Kragh Michael , Chang Jenny C. , Rosato Roberto R.
Published: May 2020

Background

The human epidermal growth factor receptor (HER) family, notably EGFR, is overexpressed in most triple-negative breast cancer (TNBC) cases and provides cancer cells with compensatory signals that greatly contribute to the survival and development of resistance in response to therapy. This study investigated the effects of Pan-HER (Symphogen, Ballerup, Denmark), a novel mixture of six monoclonal antibodies directed against members of the HER family EGFR, HER2, and HER3, in a preclinical trial of TNBC patient-derived xenografts (PDXs).

Methods

Fifteen low passage TNBC PDX tumor samples were transferred into the right mammary fat pad of mice for engraftment. When tumors reached an average size of 100–200 mm3, mice were randomized (n ≥ 6 per group) and treated following three 1-week cycles consisting of three times/week intraperitoneal (IP) injection of either formulation buffer (vehicle control) or Pan-HER (50 mg/kg). At the end of treatment, tumors were collected for Western blot, RNA, and immunohistochemistry analyses.

Results

All 15 TNBC PDXs were responsive to Pan-HER treatment, showing significant reductions in tumor growth consistent with Pan-HER-mediated tumor downmodulation of EGFR and HER3 protein levels and significantly decreased activation of associated HER family signaling pathways AKT and ERK. Tumor regression was observed in five of the models, which corresponded to those PDX tumor models with the highest level of HER family activation.

Conclusions

The marked effect of Pan-HER in numerous HER family-dependent TNBC PDX models justifies further studies of Pan-HER in TNBC clinical trials as a potential therapeutic option.