bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin E (α‐, β + γ‐ and δ‐tocopherol) levels in plant oils
Authors: Aksoz Elif , Korkut Oguzhan , Aksit Dilek , Gokbulut Cengiz
Published: May 2020

Vitamin E is the most potent lipid‐soluble antioxidant in human plasma. The richest sources of vitamin E are plant oils. This study aims to determine the concentrations of alpha, beta + gamma and delta‐tocopherols (α‐T, β + γ‐T and δ‐T) in various plant or seed oils commonly used in food, pharmaceutics or cosmetics. Forty‐one different plant or seed oil samples were purchased and kept at +4°C in the dark until the chromatographic analysis. Analyses were performed using high‐performance liquid chromatography (HPLC) following the dilution of the oil samples with 2‐propanol in a 1:3 ratio, without further processing. Total tocopherol levels in the oils analysed ranged from 11 to 3468 mg/kg. When the highest total tocopherol levels were taken into consideration, the first five plant oils were pomegranate seeds, wheat germ, fig seed, hippophae rhamnoides and corn oils. Moreover, the wheat germ, fig seed, safflower, sunflower and hazelnut oils had highest α‐tocopherol concentration in the oils analysed. These plant or seed oils have a high potential for using in the food, pharmaceutical and cosmetic industries due to their high tocopherol contents.
Different drying methods of Pistacia Atlantica seeds: Impact on drying kinetics and selected quality properties
Authors: Yarahmadi Negar , Hojjatoleslamy Mohammad , Sedaghat Boroujeni Leila
Published: May 2020

The effect of different drying procedures on the quality characteristics of Pistacia atlantica subsp. kurdica is addressed in this work. Using five different drying methods include microwave, oven (40 and 60°C), sun, and shade, P. atlantica were dried. The variations in moisture content, drying rate, major components of essential oil, and texture property were assessed at the start and at the end points of the drying process. Comparison of the drying methods indicated that microwave drying to be most effective in lowering moisture content, while the shade drying had the lowest rate among methods. In the case of microwave, the dried seeds had highest brittleness, while the highest score for the penetration force was observed in oven 40°C. Regarding major elements of the essential oil (α‐pinene, α‐terpinen‐4‐ol, myrcene, β‐ocimene, β‐caryophyllene, and limonene), there were no significant differences between the five drying techniques, nor compared to the fresh sample. To model the drying process, six thin‐layer drying kinetic models were chosen. It was found that the Midilli–Kucuk model was the most suitable for explaining the drying curve of oven 40 and 60°C, microwave, and sun methods; Wang and Singh model was excellent to explain thin‐layer shade drying behavior of the P. atlantica seeds. In conclusion, in this study, an opportunity is represented to apply the most effective procedures to decrease the drying period and to achieve a product with appropriate safety and quality features.
Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA‐CREB pathway in oral squamous cell carcinoma
Authors: Lin Chong‐Xiang , Tu Cheng‐Wei , Ma Yi‐Ke , Ye Peng‐Cheng , Shao Xia , Yang Zhao‐An , Fang Yi‐Ming
Published: May 2020

Background/Aim

Nobiletin is a polymethoxylated flavone enriched in Citrus and is used as an important drug in traditional Chinese medicine for various kinds of diseases. Among its multiple functions, it has shown that nobiletin inhibits proliferation of various cancer cells. However, it is unclear whether nobiletin inhibits the growth of oral squamous cell carcinoma (OSCC) cells.

Materials and Methods

We explored the antitumor effects of nobiletin in TCA‐8113 and CAL‐27 oral squamous cells. The Cell Counting Kit‐8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the number of cells in the various phases of the cell cycle. PCR and Western blot were applied to determine mRNA and protein expression, respectively.

Results

Nobiletin inhibited proliferation of TCA‐8113 and CAL‐27 cells via inducing cell cycle arrest at the G1 phase. In addition, the levels of phosphorylated‐PKA and phosphorylated‐CREB were reduced in nobiletin‐treated TCA‐8113 and CAL‐27 cells. Importantly, our results showed that nobiletin treatment resulted in impaired mitochondrial function and altered glucose consumption, and pyruvate and lactate production. Lastly, nobiletin was found to inhibit the generation of xenografts in vivo. Interestingly, administration of 50 μmol/L Sp‐cAMP, a potent PKA activator, rescued all phenotypes caused by nobiletin.

Conclusions

Nobiletin inhibits OSCC cell proliferation in a mitochondria‐dependent manner, indicating that it may have a promising role in cancer treatment and attenuation of drug resistance.
Palaeoenvironmental evaluation by geochemical proxies of fluvio‐lacustrine core log from the Late Miocene–Pliocene Maritsa Iztok Basin, Bulgaria
Authors: Milakovska Zlatka , Stefanova Maya , Vladislavov Georgi , Nikolov Petar , Marinov Stefan
Published: May 2020

A sequence of three lignite seams and interlayering carbonaceous mudstone is characterized by geochemical proxies. The study is extended by the palaeoenvironmental details given by the fossil fauna (gastropods, ostracods, and fishes). The predominant minerals (quartz and kaolinite) and main oxide relations of the carbonaceous mudstone point to sand and clay washed from weathered and/or altered felsic rocks from the catchment area. The mudstone features to deposition from suspension in standing or slow to persistently moving fresh waters at the bottom of the core log, and slightly aerated, warm, fresh to low saline, acidic to alkaline waters on the top. Three communities of organisms are depicted. The first is the pre‐swamp environment characterized by standing or slow moving fresh waters and detrital organic matter deposition. The second is the environment of swamp of detrital forest trunks. Depending on the climate and water table, the main forest communities are of trees of families Cupressaceae, Taxodiaceae, and Podocarpaceae accompanied by trees of family Betulaceae, and herbaceous plants. Different Sphagnum species are also abundant. The dry/cold environment is reflected in the herbaceous organic matter deposition. Polar terpenoids ratio differentiates slight climatic oscillations for the samples with a strong Gymnospermae dominance. The second coal seam development reflects the optimum tectonic conditions for peat growth in a cold and dry climate leading up to 25 m lignite deposition. The third is the moss swamp environment with very fluctuating elements. At the top of the log, a Sphagnum‐dominated peat has developed.
Rheological effects on peristaltic transport of Bingham fluid through an elastic tube with variable fluid properties and porous walls
Authors: Choudhari Rajashekhar , Gudekote Manjunatha , Vaidya Hanumesh , Prasad K. V. , Khan Sami U.
Published: May 2020

The peristaltic pumping of non‐Newtonian material configured by a tube is quite interesting phenomenon to examine the behavior of physiological fluids. The present paper investigates the role of variable viscosity and thermal conductivity on the peristaltic mechanism of Bingham fluid in an elastic tube with porous and convective boundary conditions. The long wavelength and small Reynolds number approximation is used to obtain the analytical solutions for velocity, plug flow velocity, streamlines, flow rate, and temperature. The theoretical determination of flux is calculated using the equilibrium condition, and an application to flow through an artery is highlighted by using the tension relation in an elastic tube. It is observed that the rate of flow within the elastic tube declined with variation of variable viscosity. An enhanced temperature distribution near the tube axis has been observed with increment of variable viscosity. An increasing influence of the porous parameter in the bolus size can also be seen from the streamlines plotted.
Ecotoxicological Assessment of the Doce River Surface Water After the Fundão Dam Collapse
Authors: Mendes Lucas Bueno , de Mello Fernando Aquinoga , Chagas Kátia Regina , Campelo Rodolfo Pessotti Messner , Medeiros Laila Carine Campos , Smith Ross Edward William , Furley Tatiana Heid
Published: May 2020

On 5 November 2015, the Samarco Fe ore mining operations released approximately 50 million cubic meters of mining waste into the environment, due to a dam collapse. Aiming at understanding the potential effects on the Doce River, different regions of the course of tailings were monitored using acute and chronic ecotoxicological tests with 4 species: Ceriodaphnia dubia, Daphnia similis, Danio rerio, and Vibrio fischeri. The results showed no acute toxicity for water column organisms. However, chronic toxicity was observed with the tests with the microcrustacean C. dubia, mainly related to the physical effects of the passage of flood wave and increased suspended solids, given that toxicity was reduced after filtering the samples. The results showed different magnitudes of impact among the upper, middle, and lower Doce River, with greater impact close to the dam failure area. Integr Environ Assess Manag 2020;16:608–614. © 2020 SETAC
Stillbirth at term: Does size really matter?
Authors: Coutinho Conrado Milani , Melchiorre Karen , Thilaganathan Basky
Published: May 2020

Placental dysfunction has a deleterious influence on fetal size and is associated with higher rates of perinatal morbidity and mortality. This association underpins the strategy of fetal size evaluation as a mechanism to identify placental dysfunction and prevent stillbirth. The optimal method of routine detection of small for gestational age (SGA) remains to be clarified with choices between estimation of symphyseal‐fundal height versus routine third‐trimester ultrasound, various formulae for fetal weight estimation by ultrasound, and the variable use of national, customized, or international fetal growth references. In addition to these controversies, the strategy for detecting SGA is further undermined by data demonstrating that the relationship between fetal size and adverse outcome weakens significantly with advancing gestation such that near term, the majority of stillbirths and adverse perinatal outcomes occur in normally sized fetuses. The use of maternal serum biochemical and Doppler parameters near term appears to be superior to fetal size in the identification of fetuses compromised by placental dysfunction and at increased risk of damage or demise. Multiparameter models and predictive algorithms using maternal risk factors, and biochemical and Doppler parameters have been developed, but need to be prospectively validated to demonstrate their effectiveness.
Safe abortion amid the COVID‐19 pandemic: The case of Italy
Authors: Bellizzi Saverio , Ronzoni Anna R. , Pichierri Giuseppe , Cegolon Luca , Salaris Paola , Panu Napodano Catello M. , Fiamma Maura
Published: May 2020

Improvement of women’s access to abortion care in Italy during the COVID‐19 pandemic is critical.
Update on clinical outcomes of women with COVID‐19 during pregnancy
Authors: Zeng Yingchun , Lin Lin , Yan Qiaoyuan , Wei Wei , Xiang Yang Bing , Huang Run , He Fang , Chen Dunjin
Published: May 2020

Most women with COVID‐19 delivered at or beyond the late preterm period. Some who delivered prematurely had other medical indications for preterm birth.
A fast and high frame rate adaptive beamforming using DCT‐based RF‐line recovery in line‐by‐line ultrasound imaging
Authors: Afrakhteh Sajjad , Behnam Hamid
Published: May 2020

Ultrasound imaging is an important modality used in medical imaging. One of the significant stages in the ultrasound imaging is the beamforming process. This article proposes a new technique for reducing the overall computational time of adaptive linear ultrasound imaging. The method uses the discrete cosine transform‐based reconstruction for missing data imputation. The novelty of the paper is that we do not need to beam‐form the total scan lines, so the time of image construction can be saved significantly. In other words, a fraction of the total scan lines is selected for beamforming and the others are assumed to have values as Not‐a‐Number (NaN). The proposed reconstruction technique tries to assign appropriate values to the NaN ones. We applied the proposed method to the simulated and experimental radio frequency (RF) datasets for resolution and contrast evaluation. Results showed that the proposed technique is near to the minimum variance (MV) method in terms of resolution and contrast, and has less computational time for image formation compared to the MV. As some quantitative examples in some experiments we have formed only 50% and 33% of the total lines and reconstructed the rest, then we have been able to increase the frame rate twice and three times, respectively, which can be very useful in many applications, especially in echocardiography imaging. In addition, since the execution time of the reconstruction algorithm is not very significant, we were also able to increase the speed by two and three times while achieving an error of less than 10% compared to the case of using all image lines.
Desferoxamine protects against glucocorticoid‐induced osteonecrosis of the femoral head via activating HIF‐1α expression
Authors: Jing Xingzhi , Du Ting , Yang Xiaoxia , Zhang Weimin , Wang Guodong , Liu Xiaoyang , Li Tao , Jiang Zhensong
Published: May 2020

Glucocorticoid‐induced osteonecrosis of the femoral head (GIOFH) is one of the most common complications of glucocorticoid administration. By chelating Fe2+, desferoxamine (DFO) was reported to be able to activate the HIF‐1α/VEGF pathway and promote angiogenesis. In the present study, we examined whether DFO administration could promote angiogenesis and bone repair in GIOFH. GIOFH was induced in rats by methylprednisolone in combination with lipopolysaccharide. Bone repair was assessed by histologic analysis and microcomputed tomography (micro‐CT). Vascularization was assessed by Microfil perfusion and micro‐CT analysis. Immunohistochemical staining was performed to analyze the expression of HIF‐1α, VEGF, and CD31. Our in vivo study revealed that DFO increased HIF‐1α/VEGF expression and promoted angiogenesis and osteogenesis in GIOFH. Moreover, our in vitro study revealed that DFO restored dexamethone‐induced HIF‐1α downregulation and angiogenesis inhibition. Besides, our in vitro study also demonstrated that DFO could protect bone marrow‐derived stem cells from dexamethone‐induced apoptosis and mitochondrial dysfunction by promoting mitophagy and mitochondrial fission. In summary, our data provided useful information for the development of novel therapeutics for management of GIOFH.
Pharmacokinetics and Safety of Ranirestat in Patients With Hepatic Impairment
Authors: Itou Minoru , Fujita Tomoe , Inoue Kazuaki , Uchida Naoki , Takagaki Takeshi , Ishii Daisuke , Kakuyama Hiroyoshi
Published: May 2020

Ranirestat is an aldose reductase inhibitor hypothesized to improve diabetic neuropathy. An open‐label, single‐dose, parallel‐group study was conducted to compare pharmacokinetic (PK) characteristics of an oral dose of ranirestat across subjects with normal hepatic function and patients with mild and moderate hepatic impairment because ranirestat is expected to be used by patients with diabetes mellitus, possibly including those with hepatic impairment. To evaluate the necessity for dose adjustment, PK profiles and tolerability were studied at the dose of 40 mg, the expected optimal clinical dose in patients with diabetic neuropathy and normal hepatic function. In total, 20 subjects, including 5, 10, and 5 subjects with normal hepatic function, mild hepatic impairment, and moderate hepatic impairment, respectively, completed the study. Serial PK sampling was conducted up to 504 hours, and PK parameters were calculated and compared between healthy subjects and patients with mild or moderate hepatic impairment. The geometric mean ratios of peak concentration and area under the concentration‐time curve in patients with mild hepatic impairment (90%CI) were 86.7% (55.3% to 135.9%) and 84.7% (68.5% to 104.8%), respectively. The values in patients with moderate hepatic impairment were 81.3% (48.8% to 135.5%) and 91.7% (72.1% to 116.7%), respectively. These results demonstrated that plasma ranirestat exposure and the plasma protein binding of the drug were not substantially altered by normal, mild, or moderate hepatic impairment (protein binding 99.22%, 99.29%, and 99.00%, respectively). All adverse events were mild in severity. Based on these findings, no dose adjustment will be required for ranirestat in patients with mild or moderate hepatic impairment.
Long‐term human IgG treatment improves heart and muscle function in a mouse model of Duchenne muscular dystrophy
Authors: Zschüntzsch Jana , Jouvenal Pia Vanessa , Zhang Yaxin , Klinker Florian , Tiburcy Malte , Liebetanz David , Malzahn Dörthe , Brinkmeier Heinrich , Schmidt Jens
Published: May 2020

Background

Duchenne muscular dystrophy (DMD) is a progressive muscle‐wasting disease caused by mutations in the dystrophin gene, which leads to structural instability of the dystrophin–glycoprotein‐complex with subsequent muscle degeneration. In addition, muscle inflammation has been implicated in disease progression and therapeutically addressed with glucocorticosteroids. These have numerous adverse effects. Treatment with human immunoglobulin G (IgG) improved clinical and para‐clinical parameters in the early disease phase in the well‐established mdx mouse model. The aim of the present study was to confirm the efficacy of IgG in a long‐term pre‐clinical study in mdx mice.

Methods

IgG (2 g/kg body weight) or NaCl solution as control was administered monthly over 18 months by intraperitoneal injection in mdx mice beginning at 3 weeks of age. Several clinical outcome measures including endurance, muscle strength, and echocardiography were assessed. After 18 months, the animals were sacrificed, blood was collected for analysis, and muscle samples were obtained for ex vivo muscle contraction tests, quantitative PCR, and histology.

Results

IgG significantly improved the daily voluntary running performance (1.9 m more total daily running distance, P < 0.0001) and slowed the decrease in grip strength by 0.1 mN, (P = 0.018). IgG reduced fatigability of the diaphragm (improved ratio to maximum force by 0.09 ± 0.04, P = 0.044), but specific tetanic force remained unchanged in the ex vivo muscle contraction test. Cardiac function was significantly better after IgG, especially fractional area shortening (P = 0.012). These results were accompanied by a reduction in cardiac fibrosis and the infiltration of T cells (P = 0.0002) and macrophages (P = 0.0027). In addition, treatment with IgG resulted in a significant reduction of the infiltration of T cells (P ≤ 0.036) in the diaphragm, gastrocnemius, quadriceps, and a similar trend in tibialis anterior and macrophages (P ≤ 0.045) in gastrocnemius, quadriceps, tibialis anterior, and a similar trend in the diaphragm, as well as a decrease in myopathic changes as reflected by a reduced central nuclear index in the diaphragm, tibialis anterior, and quadriceps (P ≤ 0.002 in all).

Conclusions

The present study underscores the importance of an inflammatory contribution to the disease progression of DMD. The data demonstrate the long‐term efficacy of IgG in the mdx mouse. IgG is well tolerated by humans and could preferentially complement gene therapy in DMD. The data call for a clinical trial with IgG in DMD.
Multiple forms of discrimination and internalized stigma compromise retention in HIV care among adolescents: findings from a South African cohort
Authors: Pantelic Marija , Casale Marisa , Cluver Lucie , Toska Elona , Moshabela Mosa
Published: May 2020

Introduction

Efficacious antiretroviral treatment (ART) enables people to live long and healthy lives with HIV but young people are dying from AIDS‐related causes more than ever before. Qualitative evidence suggest that various forms of HIV‐related discrimination and resulting shame act as profound barriers to young people’s engagement with HIV services. However, the impact of these risks on adolescent retention in HIV care has not been quantified. This study has two aims: (1) to examine whether and how different types of discrimination compromise retention in care among adolescents living with HIV in South Africa; and (2) to test whether internalized stigma mediates these relationships.

Methods

Between 2014 and 2017, adolescents living with HIV (aged 10 to 19) from 53 health facilities in the Eastern Cape, South Africa, were interviewed at baseline (n = 1059) and 18‐month follow‐up (n = 979, 92.4%), with responses linked to medical records. Data were analysed through multiple regression and mediation models.

Results

About 37.9% of adolescents reported full retention in care over the 2‐year period, which was associated with reduced odds of viral failure (OR: 0.371; 95% CI: .224, .614). At baseline, 6.9% of adolescents reported discrimination due to their HIV status; 14.9% reported discrimination due to HIV in their families and 19.1% reported discrimination in healthcare settings. Healthcare discrimination was associated with reduced retention in care both directly (effect: −0.120; CI: −0.190, −0.049) and indirectly through heightened internalized stigma (effect: 0.329; 95% CI: 0.129, 0.531). Discrimination due to family HIV was associated with reduced retention in care both directly (effect: −0.074, CI: −0.146, −0.002) and indirectly through heightened internalized stigma (effect: 0.816, CI: 0.494, 1.140). Discrimination due to adolescent HIV was associated with reduced retention in care only indirectly, through increased internalized stigma (effect: 0.408; CI: 0.102, 0.715).

Conclusions

Less than half of adolescents reported 2‐year retention in HIV care. Multiple forms of discrimination and the resultant internalized stigma contributed to this problem. More intervention research is urgently needed to design and test adolescent‐centred interventions so that young people living with HIV can live long and healthy lives in the era of efficacious anti‐retroviral treatment.
The value of clinical parameters in predicting the severity of COVID‐19
Authors: Shang Weifeng , Dong Junwu , Ren Yali , Tian Ming , Li Wei , Hu Jianwu , Li Yuanyuan
Published: May 2020

To study the relationship between clinical indexes and the severity of coronavirus disease 2019 (COVID‐19), and to explore its role in predicting the severity of COVID‐19. Clinical data of 443 patients with COVID‐19 admitted to our hospital were retrospectively analyzed, which were divided into nonsevere group (n = 304) and severe group (n = 139) according to their condition. Clinical indicators were compared between different groups. The differences in sex, age, the proportion of patients with combined heart disease, leukocyte, neutrophil‐to‐lymphocyte ratio (NLR), neutrophil, lymphocyte, platelet, D‐dimer, C‐reactive protein (CRP), procalcitonin, lactate dehydrogenase, and albumin on admission between the two groups were statistically significant (P  <  .05). Multivariate logistic regression analysis showed NLR and CRP were independent risk factors for severe COVID‐19. Platelets were independent protective factors for severe COVID‐19. The receiver operating characteristic (ROC) curve analysis demonstrated area under the curve of NLR, platelet, CRP, and combination was 0.737, 0.634, 0.734, and 0.774, respectively. NLR, CRP, and platelets can effectively assess the severity of COVID‐19, among which NLR is the best predictor of severe COVID‐19, and the combination of three clinical indicators can further predict severe COVID‐19.
Increase in COVID‐19 cases and case‐fatality and case‐recovery rates in Europe: A cross‐temporal meta‐analysis
Authors: Karadag Engin
Published: May 2020

The new coronavirus (COVID‐19) infection reported in China in December 2019 has become a pandemic in a few weeks, affecting the entire world. In this respect, it is crucial to determine the case‐increase, case‐fatality, and case‐recovery rates to control COVID‐19. In this study, the case‐increase, case‐fatality, and case‐recovery rates of COVID‐19 in 36 European countries were analyzed with the meta‐analysis method using data released by the health organizations and WHO. The data were obtained from the website of health organizations of 36 European countries and the website of WHO until 11 May 2020. The analyses were carried out on 1 744 704 COVID‐19‐diagnosed cases in 36 European countries. The case‐increase, case‐fatality and case‐recovery rates of COVID‐19 were calculated using 95% confidence intervals (95% CI), single‐arm meta‐analysis, cross‐temporal meta‐analysis, and meta‐regression random‐effects model. The standardized case‐increase rate of COVID‐19 is 5% (95% CI [0.040, 0.063]) and the average case‐increase rate in European countries has started to decline by around 3% (95% CI [0.047, 0.083]) weekly. The countries with the highest rate of case increase are Belgium, Sweden, Russia, the Netherlands and the United Kingdom. Although the case‐fatality rate of COVID‐19 patients was 4.5% as of May 11 (95% CI [0.037‐0.055]), this rate is 6.3% (95% CI [0.047, 0.083]) in standardized time (6th week). The case‐recovery rates of patients are 46% (95% CI [0.376‐0.547]). This study presents important results regarding the COVID‐19 pandemic in Europe. Although the rate of increase in new COVID‐19 cases has dropped, there is not much decline in the case‐fatality rates and no increase in case‐recovery rates. The case‐fatality rate of COVID‐19 in Europe was estimated to be in the range of 4% to 4.5% and a minimum of 4 weeks (as of 11 May) is expected to have the figure below 1% in a country with an average case‐increase rate. Monitoring case fatalities in Belgium, the Netherlands and Sweden, and treatment successes in Germany and Austria play a role of utmost importance.
Hepatic complications of COVID‐19 and its treatment
Authors: Tian Dandan , Ye Qing
Published: May 2020

Coronavirus disease 2019 (COVID‐19) is highly contagious and has a variety of clinical manifestations, it can affect a number of other organs in addition to the lungs, and liver injury may occur. Severe acute respiratory syndrome coronavirus 2 can cause liver injury through systemic inflammatory response syndrome, cytokine storms, ischemia‐reperfusion injury, side effects of treatment drugs, and underlying liver disease and can attack liver cells directly via angiotensin‐converting enzyme 2. Clinical studies have found that liver injury in COVID‐19 patients mainly manifests as abnormal liver biochemical indicators, but there have been no reports of liver failure caused by this disease. The number of COVID‐19 patients with liver injury is increasing, and the incidence of liver injury in COVID‐19 patients with severe disease are higher than in patients with mild disease. Liver injury may be a risk factor, which worsens in patients with COVID‐19, and hence it is necessary to pay attention to the occurrence of liver injury in the diagnosis and treatment of COVID‐19.
Obesity predisposes to the risk of higher mortality in young COVID‐19 patients
Authors: Zhang Fengqin , Xiong Ying , Wei Yanqiu , Hu Yi , Wang Feng , Li Gang , Liu Kui , Du Ronghui , Wang Cong‐Yi , Zhu Wenzhen
Published: May 2020

Although emerging data demonstrated mortality of young COVID‐19 patients, no data have reported the risk factors of mortality for these young patients, and whether obesity is a risk for young COVID‐19 patients remains unknown. We conducted a retrospective study including 13 young patients who died of COVID‐19 and 40 matched survivors. Logistic regression was employed to characterize the risk factors of mortality in young obese COVID‐19 patients. Most of the young deceased COVID‐19 patients were mild cases at the time of admission, but the disease progressed rapidly featured by a higher severity of patchy shadows (100.00% vs 48.70%; P = .006), pleural thickening (61.50% vs 12.80%; P = .012), and mild pericardial effusion (76.90% vs 0.00%; P < .001). Most importantly, the deceased patients manifested higher body mass index (odds ratio [OR] = 1.354; 95% confidence interval [CI] = 1.075‐1.704; P = .010), inflammation‐related index C‐reactive protein (OR = 1.014; 95% CI = 1.003‐1.025; P = .014), cardiac injury biomarker hs‐cTnI (OR = 1.420; 95% CI = 1.112‐1.814; P = .005), and increased coagulation activity biomarker D‐dimer (OR = 418.7; P = .047), as compared with that of survivors. Our data support that obesity could be a risk factor associated with high mortality in young COVID‐19 patients, whereas aggravated inflammatory response, enhanced cardiac injury, and increased coagulation activity are likely to be the mechanisms contributing to the high mortality.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Technical considerations and the learning curve
Authors: Vining Charles C. , Izquierdo Francisco , Eng Oliver S. , Turaga Kiran K.
Published: May 2020

Over the past decade, there has been a considerable increase in the utilization of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of patients with peritoneal metastases. This is due to improved safety and favorable oncologic outcomes, including curative potential. CRS/HIPEC has a steep learning curve and requires familiarity with peritonectomy procedures. This review will outline the technical aspects and learning curve of CRS/HIPEC.
A retrospective pilot study to examine the feasibility of real‐time navigation for laparoscopic liver resections in intrahepatic cholangiocarcinoma using fusion indocyanine green fluorescence imaging
Authors: Zhai Shu‐Ting , Liang Xiao , Mao Qi‐Jiang , Liang Yue‐Long , Xu Jun‐Jie , Chen Jiang , Shi Liang , Xie Yang‐Yang , Cai Xiu‐Jun
Published: May 2020

Background and Objectives

Recently, PINPOINT, a novel laparoscopic fusion indocyanine green fluorescence imaging (IGFI) system has become available for laparoscopic liver resection. This study aims to characterize fluorescence patterns of intrahepatic cholangiocarcinoma (ICC) using the negative counterstaining method in laparoscopic anatomical hepatectomies of ICC.

Methods

Eleven consecutive patients, diagnosed with intrahepatic cholangiocarcinoma and underwent laparoscopic liver resection between April 2017 and December 2018, were retrospectively reviewed. A laparoscopic IGFI navigation system was used to characterize fluorescence patterns of ICC with intraoperative liver segment demarcation by means of negative counterstaining.

Results

Fusion IGFI of ICC was successfully obtained from all 11 patients from the surgical specimens. The fluorescence patterns of ICC can be categorized into rim‐type fluorescence and segmental fluorescence, depending on tumor growth. In eight patients, indocyanine green fluorescence imaging was used to identify the hepatic lobes or segments by negative counterstaining. In six cases, a valid and persistent demarcation was achieved intraoperatively.

Conclusion

Laparoscopic IGFI system could identify different types of ICC lesions and may facilitate real‐time navigation for laparoscopic anatomic liver resection of ICC.
A nomogram to predict non–sentinel lymph node metastasis in patients with initial cN+ breast cancer that downstages to cN0 after neoadjuvant chemotherapy
Authors: Cheng Minyi , Zhuang Xiaosheng , Zhang Liulu , Zhu Teng , Lin Yufeng , Yang Mei , Ji Fei , Yang Ciqiu , Gao Hongfei , Wang Kun
Published: May 2020

Background and Objectives

This study mainly explored the factors that influence non–sentinel lymph node (NSLN) metastasis in patients with breast cancer (BC) whose axillary lymph nodal status changed from clinically node positive (cN+) to clinically node negative (cN0) after neoadjuvant chemotherapy (NAC).

Methods

We retrospectively analyzed the clinicopathological factors affecting NSLN metastasis in a total of 179 patients with cN+ BC downstaged to cN0 (120 in the training set and 59 in the validation set) who underwent both sentinel lymph node (SLN) biopsy and axillary lymph node dissection following NAC.

Results

Among 179 patients enrolled, the overall NSLN metastatic rate was 24.0% (95% confidence interval [CI]: 17.7%‐30.3%). In multivariate logistic regression analysis, the number of positive SLNs achieving a pathological complete remission of the breast and clinical node staging was independent predictors of NSLN metastasis. A nomogram was established based on these factors and displayed a good discriminatory capability, with an area under the curve of 0.919 (95% CI: 0.865‐0.973) for the training set and 0.900 (95% CI: 0.812‐0.988) for the validation set and its clinical utility was confirmed by the decision curve analysis.

Conclusions

The nomogram established showed the ability to predict NSLN metastases in patients with initial cN+ BC that downstaged to cN0 after NAC.
Ultrasound May Help Detect Chest Wall Recurrence After Mastectomy at an Early Stage
Authors: Wang Ying , Liu Danru , Wu Zhifeng
Published: May 2020

Objectives

To define ultrasound (US) features that help diagnose local recurrence (LR) and differentiate benign masses from LR chest wall masses after mastectomy in patients with breast cancer.

Methods

The US and surgical records of 119 pathologically confirmed chest wall masses in 101 patients were reviewed from 4634 patients with breast cancer who underwent mastectomies. The chest wall masses were divided into 2 groups depending on their longitudinal diameter (LD; ≤10 and > 10 mm). The US features of the subgroups, depending on their nature (benign and LR), were analyzed and compared.

Results

Among 119 masses, 58 (48.74%) were benign masses, and 61 (51.26%) were LR masses. For LR, the mean area under the curve ± SD, sensitivity, and specificity of US were 0.849 ± 0.033, 85.25%, and 84.48% (P < .001), respectively. Among the US characteristics, vascularity, an irregular shape, and a location in deep layers were the top 3 factors related to LR (odds ratios, 4.0, 2.6, and 2.2). To diagnose LR by US, judging the anatomic layer of the locations of masses with an LD of 10 mm or less and the presence of vascularity in masses with an LD of greater than 10 mm were helpful.

Conclusions

Ultrasound is a relatively accurate and objective method to differentiate LR from a benign mass after mastectomy with follow‐up. Judging the anatomic layer of the mass location with US likely increases the accuracy of LR diagnosis at an early stage.
Effects of Neurod1 Expression on Mouse and Human Schwannoma Cells
Authors: Kersigo Jennifer , Gu Lintao , Xu Linjing , Pan Ning , Vijayakuma Sarath , Jones Timothy , Shibata Seiji B. , Fritzsch Bernd , Hansen Marlan R.
Published: May 2020

Objectives

The objective was to explore the effect of the proneuronal transcription factor neurogenic differentiation 1 (Neurod1, ND1) on Schwann cells (SC) and schwannoma cell proliferation.

Methods

Using a variety of transgenic mouse lines, we investigated how expression of Neurod1 effects medulloblastoma (MB) growth, schwannoma tumor progression, vestibular function, and SC cell proliferation. Primary human vestibular schwannoma (VS) cell cultures were transduced with adenoviral vectors expressing Neurod1. Cell proliferation was assessed by 5‐ethynyl‐2'‐deoxyuridine (EdU) uptake.

Study Design

Basic science investigation.

Results

Expression of Neurod1 reduced the growth of slow‐growing but not fast‐growing MB models. Gene transfer of Neurod1 in human schwannoma cultures significantly reduced cell proliferation in dose‐dependent way. Deletion of the neurofibromatosis type 2 (Nf2) tumor‐suppressor gene via Cre expression in SCs led to increased intraganglionic SC proliferation and mildly reduced vestibular sensory‐evoked potentials (VsEP) responses compared to age‐matched wild‐type littermates. The effect of Neurod1‐induced expression on intraganglionic SC proliferation in animals lacking Nf2 was mild and highly variable. Sciatic nerve axotomy significantly increased SC proliferation in wild‐type and Nf2‐null animals, and expression of Neurod1 reduced the proliferative capacity of both wild‐type and Nf2‐null SCs following nerve injury.

Conclusion

Expression of Neurod1 reduces slow‐growing MB progression and reduces human SC proliferation in primary VS cultures. In a genetic mouse model of schwannomas, we find some effects of Neurod1 expression; however, the high variability indicates that more tightly regulated Neurod1 expression levels that mimic our in vitro data are needed to fully validate Neurod1 effects on schwannoma progression.

Level of Evidence

NA Laryngoscope, 131:E259–E270, 2021
Simul‐staining manganese oxides and microbial cells
Authors: Cavazos Amanda R. , Glass Jennifer B.
Published: May 2020

Manganese oxide minerals (Mn(III/IV)Ox) are ubiquitous in natural environments and interactions between Mn(III/IV)Ox and microbes play important roles in biogeochemical cycles. Current techniques for determining the spatial distribution of microbes with Mn(III/IV)Ox include electron microscopy and synchrotron radiation analyses. However, these techniques may not be readily available in most laboratories or may be cost prohibitive. Here we present a rapid, cost‐effective “simul‐staining” method for imaging particulate Mn(III/IV)Ox and cells on the same filter using epifluorescence microscopy with differential interference contrast (DIC) capability as a prescreening tool before higher resolution and/or more time‐intensive analyses. This method uses leucoberbelin blue (LBB) dye, which turns blue when oxidized by particulate Mn(III/IV)Ox on filters, and the fluorescent nucleic acid stain, SYBR Green, which fluoresces when bound to nucleic acids. First, the DIC configuration is used to locate blue “haloes” of oxidized LBB around Mn(III/IV)Ox particles. Second, a filter set that excites dyes with blue light and emits green fluorescence is used to image SYBR Green bound to nucleic acids in cells. Third, ImageJ is used for image analysis to associate Mn(III/IV)Ox particles and microbes. We demonstrate that this simul‐staining is suitable for laboratory cultures of manganese‐oxidizing bacteria as well as environmental samples from a marine oxycline.
Indeterminate thyroid nodules in the era of molecular genomics
Authors: Rao Sarika N. , Bernet Victor
Published: May 2020

Background

Indeterminate thyroid nodules are diagnosed in up to 30% of fine‐needle aspirations and the risk of malignancy in these cases are highly variable. Consequently, managing these nodules has been a challenge. While a diagnostic thyroidectomy would help clarify the pathology, there is the risk of developing surgical‐related complications for a procedure that may not have been necessary and associated high costs. Genomic testing of indeterminate thyroid nodules may help better guide management.

Methods

We present an unbiased comprehensive review of available molecular testing for classifying indeterminate thyroid nodules, as well as their strengths and limitations, with the objective to allow practitioners to choose the best testing modality for their patients.

Results

Molecular testing of these nodules provided a platform to help distinguish benign versus malignant nodules, providing more confidence to rule in or rule out the likelihood of thyroid cancer in indeterminate nodules.

Conclusion

Genomic testing has evolved to more comprehensive panels to better stratify indeterminate nodules, including Hürthle cell neoplasms and noninvasive follicular neoplasm with papillary‐like nuclear features. Understanding the methodology of each available test improves patient care and reduces unnecessary costs.
Behavioral Circadian Timing System Disruptors and Incident Type 2 Diabetes in a Nonshift Working Multiethnic Population
Authors: Muilwijk Mirthe , Stenvers Dirk Jan , Nicolaou Mary , Kalsbeek Andries , van Valkengoed Irene G.M.
Published: May 2020

Objective

This study aimed to describe distributions of behavioral circadian disruptors in a free‐living setting among a nonshift working multiethnic population, estimate the associated risk of type 2 diabetes (T2D), and determine whether disruptors account for ethnic differences in T2D.

Methods

Participants from six ethnic groups were included (Amsterdam, the Netherlands; n = 1,347‐3,077 per group). Multinomial logistic regression was used to estimate ethnic differences in disruptors, such as skipping breakfast, eating erratically, and sleep duration. Associations between disruptors and incident T2D and the interaction by ethnicity were studied by Cox regression.

Results

Ethnic minority populations skipped breakfast more often, timed meals differently, had longer periods of fasting, ate more erratically, and had more short/long sleep durations than the Dutch. Night snacking from 4 am to 6 am (HR: 5.82; 95% CI: 1.42‐23.91) and both short (HR: 1.48; 95% CI: 1.03‐2.12) and long sleep (HR: 3.09; 95% CI: 1.54‐6.22), but no other disruptors, were associated with T2D. The higher T2D risk among ethnic minority populations compared with Dutch did not decrease after adjustment for last snack or length of sleep.

Conclusions

Although prevalence of circadian disruptors was higher among ethnic minority populations and some disruptors were associated with T2D, disruptors did not account for ethnic differences in T2D risk.
BMI and Cause‐Specific Hospital Admissions and Costs: The UK Biobank Cohort Study
Authors: O’Halloran Richard , Mihaylova Borislava , Cairns Benjamin J. , Kent Seamus
Published: May 2020

Objective

To estimate the effect of BMI on cause‐specific hospital admissions and costs in men and women is not well understood, and this study’s aim is to address this.

Methods

For 451,320 men and women aged 40 years or older recruited into the UK Biobank, followed up for 6 years on average, this study estimated annual rates and costs (at 2016 UK prices) of hospital admissions, overall and by diagnostic category (using International Classification of Diseases, Tenth Revision chapters), in relation to BMI.

Results

Among those who were never smokers, a 2‐kg/m2 higher BMI (above 20 kg/m2) was associated with a 6.2% (99% CI: 5.3% to 7.2%) higher admission rate and an 8.6% (99% CI: 7.3% to 10.0%) higher annual cost in men and with a 5.7% (99% CI: 4.9% to 6.6%) higher admission rate and an 8.4% (99% CI: 7.5% to 9.3%) higher annual cost in women. Higher BMI was associated with higher admission rates and costs for many types of health conditions, particularly for endocrine, skin, and musculoskeletal disorders in both men and women and for circulatory diseases in men.

Conclusions

BMI beyond healthy weight is strongly associated with higher annual rates of hospital admission and higher costs in both men and women across a wide range of health conditions.
Clinical characteristics of COVID‐19 in children: Are they similar to those of SARS?
Authors: Leung Char
Published: May 2020

Although the number of SARS‐CoV‐2 infections has been rising amid the current pandemic of COVID‐19, the low infection rate of SARS‐CoV‐2 in children has been low. By examining the clinical data available in the public domain, the present work clarifies the clinical presentations in children with COVID‐19 in China. Statistical significance tests and adjusted odds ratios estimation were performed on the children (age below 18) and adults (age 18 or above) cohorts in China. SARS‐CoV and SARS‐CoV‐2 shared similar clinical features. Lower respiratory tract infection was less prominent in children as evidenced by the relatively low prevalence in chest pain/discomfort and dyspnea. Similar to SARS, younger children had a less aggressive clinical course, compared with adolescents. While fewer symptoms were observed in children compared to adults, there is not yet sufficient evidence to conclude shorter hospital stay in children.
Model‐Based Analysis Reveals a Sustained and Dose‐Dependent Acceleration of Wound Healing by VEGF‐A mRNA (AZD8601)
Authors: Almquist Joachim , Rikard S. Michaela , Wågberg Maria , Bruce Anthony C. , Gennemark Peter , Fritsche‐Danielson Regina , Chien Kenneth R. , Peirce Shayn M. , Hansson Kenny , Lundahl Anna
Published: May 2020

Intradermal delivery of AZD8601, an mRNA designed to produce vascular endothelial growth factor A (VEGF‐A), has previously been shown to accelerate cutaneous wound healing in a murine diabetic model. Here, we develop population pharmacokinetic and pharmacodynamic models aiming to quantify the effect of AZD8601 injections on the dynamics of wound healing. A dataset of 584 open wound area measurements from 131 mice was integrated from 3 independent studies encompassing different doses, dosing timepoints, and number of doses. Evaluation of several candidate models showed that wound healing acceleration is not likely driven directly by time‐dependent VEGF‐A concentration. Instead, we found that administration of AZD8601 induced a sustained acceleration of wound healing depending on the accumulated dose, with a dose producing 50% of the maximal effect of 92 µg. Simulations with this model showed that a single dose of 200 µg AZD8601 can reduce the time to reach 50% wound healing by up to 5 days.
Clinical trials on pain lowering effect of ginger: A narrative review
Authors: Rondanelli Mariangela , Fossari Federica , Vecchio Viviana , Gasparri Clara , Peroni Gabriella , Spadaccini Daniele , Riva Antonella , Petrangolini Giovanna , Iannello Giancarlo , Nichetti Mara , Infantino Vittoria , Perna Simone
Published: May 2020

Ginger has a pain‐reducing effect and it can modulate pain through various mechanisms: inhibition of prostaglandins via the COX and LOX‐pathways, antioxidant activity, inibition of the transcription factor nf–kB, or acting as agonist of vanilloid nociceptor. This narrative review summarizes the last 10‐year of randomized controlled trials (RCTs), in which ginger was traditionally used as a pain reliever for dysmenorrhea, delayed onset muscle soreness (DOMS), osteoarthritis (AO), chronic low back pain (CLBP), and migraine. Regarding dysmenorrhea, six eligible studies suggest a promising effect of oral ginger. As concerned with DOMS, the four eligible RCTs suggested a reduction of inflammation after oral and topical ginger administration. Regarding knee AO, nine RCTs agree in stating that oral and topical use of ginger seems to be effective against pain, while other did not find significant differences. One RCT considered the use of ginger in migraine and suggested its beneficial activity. Finally, one RCT evaluated the effects of Swedish massage with aromatic ginger oil on CLBP demonstrated a reduction in pain. The use of ginger for its pain lowering effect is safe and promising, even though more studies are needed to create a consensus about the dosage of ginger useful for long‐term therapy.
Some Discovered Practices of Lay Coffee Drinkers
Authors: Fele Giolo , Liberman Kenneth
Published: May 2020

When lay coffee drinkers taste the coffee in their cups, the flavors they note are shaped by the local interaction that provides the context for the occasion. Three methods they use for identifying flavors are examined and described: clustering, or how flavor descriptors are articulated in ensembles during a collaborative process; objectivating, the concerted work of transforming tentative suggestions into objective findings; and calibrating, how drinkers align their practice of tasting in order to conform with—and make meaningful—the objectivated accounts. These microsocial practices continuously intrude upon tasting, and a serendipitously developed local order guides their taste identification. This does not mean that there is no real taste, only that the taste never stands apart from the social contingencies and the discursive practices that are developed to describe
it.