bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five-year nationwide incidence of macular hole requiring surgery in Korea
Authors: Cho Soo Chang , Park Sang Jun , Byun Seong Jun , Woo Se Joon , Park Kyu Hyung 
Published: October 2019

Background/aimsTo estimate the incidence and demographics of macular hole (MH) requiring surgery in Korea.MethodsPatients who underwent surgery for MH in Korea from 2011 to 2015 with the diagnostic code for MH and the surgical code for vitrectomy were retrospectively identified using the Korean national health claims database. The average incidence rate of MH during the 5-year study period was estimated by applying the direct method of standardisation using the 2015 census data as a reference population.ResultsA total of 7301 patients with MH requiring surgery were identified. The average incidence of MH requiring surgery was 3.14 (95 % CI, 3.07 to 3.21) per 100 000 person-years . The incidence in women (4.29 per 100 000 person-years; 95% CI, 4.17 to 4.40) was significantly higher than that in men (2.00 per 100 000 person-years; 95% CI, 1.92 to 2.07; p<0.001). The incidence rate of MH increased exponentially with increasing age between the ages of 35 years and 69 years and was highest among patients aged 65–69 years. The female-to-male ratio for the incidence of MH was 2.15:1.ConclusionsThis study represents the largest nationwide population-based investigation of the incidence of MH, using a database that covers the entire population of South Korea. MH is the disease of elderly peaked 70 years old and more common in women.
Renal denervation improves sodium excretion in rats with chronic heart failure: effects on expression of renal ENaC and AQP2
Authors: Zheng Hong , Liu Xuefei , Katsurada Kenichi , Patel Kaushik P. 
Published: October 2019

Previously we have shown that increased expression of renal epithelial sodium channels (ENaC) may contribute to the renal sodium and water retention observed during chronic heart failure (CHF). The goal of this study was to examine whether renal denervation (RDN) changed the expressions of renal sodium transporters ENaC, sodium-hydrogen exchanger-3 proteins (NHE3), and water channel aquaporin 2 (AQP2) in rats with CHF. CHF was produced by left coronary artery ligation in rats. Four weeks after ligation surgery, surgical bilateral RDN was performed. The expression of ENaC, NHE3, and AQP2 in both renal cortex and medulla were measured. As a functional test for ENaC activation, diuretic and natriuretic responses to ENaC inhibitor benzamil were monitored in four groups of rats (Sham, Sham+RDN, CHF, CHF+RDN). Western blot analysis indicated that RDN (1 wk later) significantly reduced protein levels of α-ENaC, β-ENaC, γ-ENaC, and AQP2 in the renal cortex of CHF rats. RDN had no significant effects on the protein expression of kidney NHE3 in both Sham and CHF rats. Immunofluorescence studies of kidney sections confirmed the reduced signaling of ENaC and AQP2 in the CHF+RDN rats compared with the CHF rats. There were increases in diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. RDN reduced the diuretic and natriuretic responses to benzamil in CHF rats. These findings suggest a critical role for renal nerves in the enhanced expression of ENaC and AQP2 and subsequent pathophysiology of renal sodium and water retention associated with CHF. NEW & NOTEWORTHY This is the first study to show in a comprehensive way that renal denervation initiated after a period of chronic heart failure reduces the expression of epithelial sodium channels and aquaporin 2 leading to reduced epithelial sodium channel function and sodium retention.
Ceramide–Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations
Authors: Khiste Sachin K. , Liu Zhijun , Roy Kartik R. , Uddin Mohammad B. , Hosain Salman B. , Gu Xin , Nazzal Sami , Hill Ronald A. , Liu Yong-Yu 
Published: October 2019

Abstract
Ceramide (Cer) is an active cellular sphingolipid that can induce apoptosis or proliferation-arrest of cancer cells. Nanoparticle-based delivery offers an effective approach for overcoming bioavailability and biopharmaceutics issues attributable to the pronounced hydrophobicity of Cer. Missense mutations of the protein p53, which have been detected in approximately 42% of cancer cases, not only lose the tumor suppression activity of wild-type p53, but also gain oncogenic functions promoting tumor progression and drug resistance. Our previous works showed that cellular Cer can eradicate cancer cells that carry a p53 deletion-mutation by modulating alternative pre-mRNA splicing, restoring wild-type p53 protein expression. Here, we report that new ceramide–rubusoside (Cer–RUB) nanomicelles considerably enhance Cer in vivo bioavailability and restore p53-dependent tumor suppression in cancer cells carrying a p53 missense mutation. Natural RUB encapsulated short-chain C6-Cer so as to form Cer–RUB nanomicelles (∼32 nm in diameter) that substantially enhanced Cer solubility and its levels in tissues and tumors of mice dosed intraperitoneally. Intriguingly, Cer–RUB nanomicelle treatments restored p53-dependent tumor suppression and sensitivity to cisplatin in OVCAR-3 ovarian cancer cells and xenograft tumors carrying p53 R248Q mutation. Moreover, Cer–RUB nanomicelles showed no signs of significant nonspecific toxicity to noncancerous cells or normal tissues, including bone marrow. Furthermore, Cer–RUB nanomicelles restored p53 phosphorylated protein and downstream function to wild-type levels in p53 R172H/+ transgenic mice. Altogether, this study, for the first time, indicates that natural Cer–RUB nanomicelles offer a feasible approach for efficaciously and safely targeting cancers carrying p53 missense mutations.
The First Clinical Use of a RecombinantLactococcus lactisExpressing Human Papillomavirus Type 16 E7 Oncogene Oral Vaccine: A Phase I Safety and Immunogenicity Trial in Healthy Women Volunteers
Authors: Mohseni Amir Hossein , Taghinezhad-S Sedigheh , Keyvani Hossein 
Published: October 2019

AbstractA dose-escalation, randomized, double-blind, placebo-controlled phase I clinical trial was performed in healthy Iranian volunteer women to assess the safety, tolerability, and immunogenicity of NZ8123-HPV16-optiE7 vaccine involving recombinant Lactococcus lactis expressing the codon-optimized human papillomavirus (HPV)-16 E7 oncogene. Fifty-five eligible subjects were divided into 6 cohorts based on the dosages (1 × 109, 5 × 109, and 1 × 1010 CFU/mL) of either vaccine or placebo, which were administrated orally a total of 4 times at weeks 1, 2, 4, and 8. Then, adverse events, specific serum IgG and vaginal IgA, and E7-specific IFNγ-secreting CD8+ CTL responses were evaluated. The vaccination was well tolerated by 40 subjects who completed the immunization schedule, and no serious adverse effects were reported. The IgG and IgA levels peaked at day 60, and the levels for the 5 × 109 CFU/mL and 1 × 1010 CFU/mL dose groups were higher than those for the 1 × 109 CFU/mL dose group. Time-to-peak stimulation in E7-specific IFNγ-secreting CD8+ CTL responses was seen in cervical lymphocytes 1 month after the last vaccination. Again, no significant increase was seen in the peripheral blood mononuclear cells (PBMC) of the same volunteers. CTL responses in cervical lymphocytes and PBMCs at day 90 were markedly higher in the 5 × 109 and 1 × 1010 CFU/mL groups than in the 1 × 109 CFU/mL group, demonstrating the dose dependency of NZ8123-HPV16-optiE7 vaccine following oral administration. The 6-month follow-up revealed that antibody levels decreased up to day 240; nevertheless, long-term E7-specific IFNγ-secreting CD8+ CTL responses were recorded during follow-up. Overall, the safety and immunogenicity profile achieved in this study encourages further phase II trials with the 5 × 109 CFU/mL dose vaccine.
An Orally Available Tubulin Inhibitor, VERU-111, Suppresses Triple-Negative Breast Cancer Tumor Growth and Metastasis and Bypasses Taxane Resistance
Authors: Deng Shanshan , Krutilina Raisa I. , Wang Qinghui , Lin Zongtao , Parke Deanna N. , Playa Hilaire C. , Chen Hao , Miller Duane D. , Seagroves Tiffany N. , Li Wei 
Published: October 2019

Abstract
Triple-negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases in the United States. TNBC has poorer overall prognosis relative to other molecular subtypes due to rapid onset of drug resistance to conventional chemotherapies and increased risk of visceral metastases. Taxanes like paclitaxel are standard chemotherapies that stabilize microtubules, but their clinical efficacy is often limited by drug resistance and neurotoxicities. We evaluated the preclinical efficacy of a novel, potent, and orally bioavailable tubulin inhibitor, VERU-111, in TNBC models. VERU-111 showed potent cytotoxicity against TNBC cell lines, inducing apoptosis and cell-cycle arrest in a concentration-dependent manner. VERU-111 also efficiently inhibited colony formation, cell migration, and invasion. Orally administered VERU-111 inhibited MDA-MB-231 xenograft growth in a dose-dependent manner, with similar efficacies to paclitaxel, but without acute toxicity. VERU-111 significantly reduced metastases originating from the mammary fat pad into lung, liver, and kidney metastasis in an experimental metastasis model. Moreover, VERU-111, but not paclitaxel, suppressed growth of luciferase-labeled, taxane-resistant, patient-derived metastatic TNBC tumors. In this model, VERU-111 repressed growth of preestablished axillary lymph node metastases and lung, bone, and liver metastases at study endpoint, whereas paclitaxel enhanced liver metastases relative to vehicle controls. Collectively, these studies strongly suggest that VERU-111 is not only a potent inhibitor of aggressive TNBC phenotypes, but it is also efficacious in a taxane-resistant model of metastatic TNBC. Thus, VERU-111 is a promising new generation of tubulin inhibitor for the treatment of TNBC and may be effective in patients who progress on taxanes.
Results presented in this study demonstrate the efficacy of VERU-111 in vivo and provide strong rationale for future development of VERU-111 as an effective treatment for metastatic breast cancer.
Clinical and Laboratory Predictors for Plaque Erosion in Patients With Acute Coronary Syndromes
Authors: Yamamoto Erika , Yonetsu Taishi , Kakuta Tsunekazu , Soeda Tsunenari , Saito Yoshihiko , Yan Bryan P. , Kurihara Osamu , Takano Masamichi , Niccoli Giampaolo , Higuma Takumi , Kimura Shigeki , Minami Yoshiyasu , Ako Junya , Adriaenssens Tom , Boeder Niklas F. , Nef Holger M. , Fracassi Francesco , Sugiyama Tomoyo , Lee Hang , Crea Filippo , Kimura Takeshi , Fujimoto James G. , Fuster Valentin , Jang Ik‐Kyung 
Published: October 2019

Background

Plaque erosion is responsible for 25% to 40% of patients with acute coronary syndromes (
ACS
). Recent studies suggest that anti‐thrombotic therapy without stenting may be an option for this subset of patients. Currently, however, an invasive procedure is required to make a diagnosis of plaque erosion. The aim of this study was to identify clinical or laboratory predictors of plaque erosion in patients with
ACS
to enable a diagnosis of erosion without additional invasive procedures.

Methods and Results

Patients with
ACS
who underwent optical coherence tomography imaging were selected from 11 institutions in 6 countries. The patients were classified into plaque rupture, plaque erosion, or calcified plaque, and predictors were identified using multivariable logistic modeling. Among 1241 patients with
ACS
, 477 (38.4%) patients were found to have plaque erosion. Plaque erosion was more frequent in non–
ST
‐segment elevation‐
ACS
than in ST‐segment–elevation myocardial infarction (47.9% versus 29.8%,
P
=0.0002). Multivariable logistic regression models showed 5 independent parameters associated with plaque erosion: age <68 years, anterior ischemia, no diabetes mellitus, hemoglobin >15.0 g/dL, and normal renal function. When all 5 parameters are present in a patient with non–
ST
‐segment elevation‐
ACS
, the probability of plaque erosion increased to 73.1%.

Conclusions

Clinical and laboratory parameters associated with plaque erosion are explored in this retrospective registry study. These parameters may be useful to identify the subset of
ACS
patients with plaque erosion and guide them to conservative management without invasive procedures. The results of this exploratory analysis need to be confirmed in large scale prospective clinical studies.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
03479723.
Symptoms of Depression and Risk of Abdominal Aortic Aneurysm: A HUNT Study
Authors: Nyrønning Linn Åldstedt , Stenman Malin , Hultgren Rebecka , Albrektsen Grethe , Videm Vibeke , Mattsson Erney 
Published: October 2019

Background

Depression is associated with cardiovascular diseases, but the evidence is scarce regarding depression and risk of abdominal aortic aneurysms (
AAA
). The aim was to determine whether individuals with depressive symptoms have increased risk of
AAA
.

Methods and Results

This population‐based prospective study included 59 136 participants (52.4% women) aged 50 to 106 years from the
HUNT
(Norwegian Nord‐Trøndelag Health Study). Symptoms of depression were assessed using the depression subscale of the Hospital Anxiety and Depression Scale (
HADS
). During a median follow‐up of 13 years, there were 742 incident cases of
AAA
(201 women). A total of 6401 individuals (12.3%) reported depressive symptoms (defined as
HADS
depression scale [
HADS
‐D]) ≥8) (52.5% women). The annual incidence rate of
AAA
was 1.0 per 1000 individuals. At all ages, the estimated proportion of individuals diagnosed with
AAA
was higher among those with depressive symptoms (log‐rank test,
P
<0.001). People with
HADS
‐D ≥8 were older than those with
HADS
‐D<8 (median 57.8 versus 52.3 years,
P
<0.001) and a statistically significantly higher proportion of them (
P
<0.001) were smokers, overweight or obese, and reported a history of coronary heart disease, diabetes mellitus, and hypertension. In a Cox proportional hazard regression model adjusted for these factors, individuals with depressive symptoms had a ≈30% higher risk of
AAA
than those without (hazard ratio, 1.32, 95%
CI
1.08–1.61,
P
=0.007).

Conclusions

This study shows that individuals with depressive symptoms have significantly higher risk of incident
AAA
, after adjustments for established risk factors.
Prevalence and Impact of Venous and Arterial Thromboembolism in Patients With Embolic Stroke of Undetermined Source With or Without Active Cancer
Authors: Ha Jongmok , Lee Mi Ji , Kim Suk Jae , Park Bo‐yong , Park Hyunjin , Cho Soohyun , Chung Jong‐Won , Seo Woo‐Keun , Kim Gyeong‐Moon , Bang Oh Young , Chung Chin‐Sang 
Published: October 2019

Background
An increased risk of acute ischemic stroke is recognized among patients with cancer. However, the mechanism behind cancer‐related stroke is unclear. In this study, we determined the presence of associated venous thromboembolism and arterial thromboembolism and their clinical impact on patients with cancer‐related stroke.

Methods and Results

Patients with embolic stroke of undetermined source with or without cancer were evaluated for venous thromboembolism (deep vein thrombosis [
DVT
] and/or pulmonary embolism) and arterial thromboembolism by using Doppler sonography to determine the presence of lower‐extremity
DVT
and the microembolic signal of the symptomatic cerebral circulation, respectively. Infarct volume was determined by diffusion‐weighted magnetic resonance imaging. The multivariable linear regression and Cox proportional hazard analysis were used to investigate the effect of
DVT
and microembolic signal on infarct volume and 1‐year survival, respectively. Of 142 screened patients, 118 were included (37 with, 81 without cancer). Those with cancer had a higher prevalence of
DVT
or microembolic signal than did the noncancer group (62.2% versus 19.8%;
P
<0.001). Among patients with cancer‐related stroke,
DVT
was associated with a greater infarct volume in magnetic resonance imaging (beta, 13.14; 95%
CI
, 1.62–24.66;
P
=0.028). Presence of
DVT
(hazard ratio, 16.79; 95%
CI,
2.05–137.75;
P
=0.009) and microembolic signal (hazard ratio, 8.16; 95%
CI
, 1.36–48.85;
P
=0.022) were independent predictors of poor 1‐year survival.

Conclusions
Patients with cancer‐associated embolic stroke of undetermined source have an elevated risk of associated venous thromboembolism and arterial thromboembolism, both of which have a significant negative impact on 1‐year survival. The results of this study may enhance our understanding of cancer‐associated stroke and improve risk stratification of patients with this disease.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/.Unique
identifier:
NCT
02212496
Quantitative Assessment of State-Dependent Atmospheric Motion Vector Uncertainties
Authors: Posselt Derek J. , Wu Longtao , Mueller Kevin , Huang Lei , Irion Fredrick W. , Brown Shannon , Su Hui , Santek David , Velden Christopher S. 
Published: October 2019

AbstractThis study examines the error characteristics of atmospheric motion vectors (AMVs) obtained by tracking the movement of water vapor features. A high-resolution numerical simulation of a dynamic weather event is used as a baseline, and AMVs tracked from retrieved water vapor fields are compared with the “true” winds produced by the model. The sensitivity of AMV uncertainty to time interval, AMV tracking window size, water vapor content, horizontal gradient, and wind structure is examined. AMVs are derived from the model water vapor field at a specific height and also from water vapor fields vertically blurred using smoothing functions consistent with high-spectral-resolution infrared (IR) and high-frequency microwave (MW) water vapor sounders. Uncertainties in water vapor AMVs are state dependent and are largest for regions with small water vapor content and small water vapor spatial gradient and in places where the flow runs parallel to contours of constant water vapor content. Smoothing of water vapor consistent with IR and MW retrievals does not increase AMV uncertainty; however, the yield of AMVs from IR sounders is much lower than from MW sounders because of the inability of IR sounders to retrieve water vapor below clouds. The yield and error are similar for AMVs in the lower and upper troposphere, even though the water vapor content in the upper troposphere is much smaller. The results have implications for the design of new observing systems, as well as the specification of errors when AMVs are ingested in data assimilation systems.
Multidisciplinary treatment of deep neck infection associated with descending necrotizing mediastinitis: a single-centre experience
Authors: Ma Chao , Zhou Lian , Zhao Ji-Zhi , Lin Run-Tai , Zhang Tao , Yu Li-Jiang , Shi Tian-Yin , Wang Mu 
Published: October 2019

Objective Deep neck infection (DNI) associated with descending necrotizing mediastinitis (DNM) is a highly lethal condition. This retrospective review was performed to share our experience performing multidisciplinary management of DNI associated with DNM during a 7-year period. Methods We reviewed 16 patients who had been surgically treated for DNM at Peking Union Medical College Hospital from April 2010 to July 2017. The clinical outcomes were analysed to determine the most appropriate therapeutic strategy. Results Five women and 11 men were included in this study. Their mean age was 54.9 ± 14.3 years. DNM-associated infections most commonly occurred secondary to odontogenic infections (n = 10). Thirteen patients required tracheotomy because of tracheal compression. All patients underwent unilateral or bilateral cervicotomy. Six patients with DNM localized in the upper mediastinal space underwent transcervical mediastinal drainage, while 10 patients with DNM extending to the lower mediastinum were treated by cervicotomy and video-assisted thoracoscopic surgery. Three patients died of multiple organ failure. Conclusion Multidisciplinary treatment can achieve favourable outcomes in >80% of patients with DNM. Early diagnosis, proper airway management, and adequate surgical drainage are crucial for reducing mortality in patients with DNM, and minimally invasive procedures also play an important role.
Purine versus non-purine xanthine oxidase inhibitors against cyclophosphamide-induced cardiac and bone marrow toxicity in rats
Authors: El-Sheikh AA , Abdelzaher WY , Gad AA , Abdel-Gaber SA 
Published: October 2019

Background and aim: Cancer is a fatal and serious disease. Cyclophosphamide (CYC) is a commonly used anticancer drug. Cardiotoxicity and myelotoxicity are life-threatening side effects of CYC treatment. We aimed to evaluate the effect of the xanthine oxidase (XO) inhibitors, allopurinol (ALL) and febuxostat (FEB), on CYC-induced cardio- and hematopoietic toxicity in rats. Methods: ALL (100 mg/kg/day) or FEB (10 mg/kg/day) were administered orally to rats in the presence and absence of CYC (200 mg/kg kg i.p. single dose) treatment. Serum creatine kinase-MB creatine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH) activities were estimated. Complete blood counting (CBC), cardiac and bone marrow XO activity, malondialdehyde level, and superoxide dismutase activity were determined. Cardiac and bone marrow histopathological changes were also evaluated. Results: ALL and FEB significantly decreased CK-MB and LDH induced by CYC. Disturbed levels of XO, oxidative stress parameters, and CBC were also corrected by both XO inhibitors tested, with amelioration of cardiac histopathological changes caused by CYC. Treatment with FEB, but not ALL, prior to CYC challenges normalized bone marrow histopathological changes. Conclusion: These results suggest that both XO inhibitors tested; ALL and FEB can ameliorate CYC-induced cardiotoxicity. However, only FEB can protect against CYC-induced myelotoxicity, whereas ALL, to the contrary, might aggravate it.
Improving care quality with prison telemedicine: The effects of context and multiplicity on successful implementation and use
Authors: Edge Chantal , Black Georgia , King Emma , George Julie , Patel Shamir , Hayward Andrew 
Published: October 2019

Background Prison telemedicine can improve the access, cost and quality of healthcare for prisoners, however adoption in prison systems worldwide has been variable despite these demonstrable benefits. This study examines anticipated and realised benefits, barriers and enablers for prison telemedicine, thereby providing evidence to improve the chances of successful implementation. Methods A systematic search was conducted using a combination of medical subject headings and text word searches for prisons and telemedicine. Databases searched included: PubMed, Embase, CINAHL Plus, PsycINFO, Web of Science, Scopus and International Bibliography of the Social Sciences. Articles were included if they reported information regarding the use of/advocacy for telemedicine, for people residing within a secure correctional facility. A scoping summary and subsequent thematic qualitative analysis was undertaken on articles selected for inclusion in the review, to identify issues associated with successful implementation and use. Results One thousand, eight hundred and eighty-two non-duplicate articles were returned, 225 were identified for full text review. A total of 163 articles were included in the final literature set. Important considerations for prison telemedicine implementation include: differences between anticipated and realised benefits and barriers, differing wants and needs of prison and community healthcare providers, the importance of top-down and bottom-up support and consideration of logistical and clinical compatibility. Conclusions When implemented well, patients, prison and hospital staff are generally satisfied with telemedicine. Successful implementation requires careful consideration at outset of the partners to be engaged, the local context for implementation and the potential benefits that should be communicated to encourage participation.