bluuebunny/crossref_metadata_2025 huggingface dataset:
Clathrin‐mediated EGFR endocytosis as a potential therapeutic strategy for overcoming primary resistance of EGFR TKI in wild‐type EGFR non‐small cell lung cancer
Authors: Kim Boyeon , Park Young Soo , Sung Jae Sook , Lee Jong Won , Lee Saet Byeol , Kim Yeul Hong
Published: December 2020

Objectives

Oncogenic alterations of epidermal growth factor receptor (EGFR) signaling are frequently noted in non‐small cell lung cancer (NSCLC). In recent decades, EGFR tyrosine kinase inhibitors (TKIs) have been developed, although the therapeutic efficacy of these inhibitor is restricted to EGFR‐mutant patients.

In this study, we investigated that clathrin‐mediated EGFR endocytosis hampers the effects of gefitinib and sustains NSCLC cells with wild‐type EGFR.

Materials and Methods

NSCLC cell lines (H358, Calu‐3, SNU‐1327, and H1703) were stimulated with the EGF and treated with gefitinib and endocytosis inhibitors (phenylarsine oxide (PAO) and Filipin III). Growth inhibition and apoptosis were evaluated. Immunofluorescence, immunoprecipitation, and western blot assay were performed to investigate EGFR endocytosis and determine the signaling pathway. Xenograft mouse models were used to verify the combination effect of gefitinib and PAO in vivo.

Results

We confirmed the differences in EGFR endocytosis according to gefitinib response in wild‐type EGFR NSCLC cell lines. EGFR in gefitinib‐sensitive and ‐refractory cell lines tended to internalize through distinct routes, caveolin‐mediated endocytosis (CVE), and clathrin‐mediated endocytosis (CME). Interestingly, while suppressing CME and CVE did not affect cell survival in sensitive cell lines significantly, CME inhibition combined with gefitinib treatment decreased cell survival and induced apoptosis in gefitinib‐refractory cell lines. In addition, blocking CME in the refractory cell lines led to downregulate of p‐STAT3 and inhibit nuclear localization of STAT3 in vivo, combination treatment with gefitinib and a CME inhibitor resulted in tumor regression accompanying apoptosis in xenograft mouse models.

Conclusion

Clathrin‐mediated EGFR endocytosis contribute primary resistance of gefitinib treatment and CME inhibition combined with gefitinib could be an option in treatment of wild‐type EGFR NSCLC.
Tip fracture of the crown of orbital atherectomy device in angulated left circumflex lesion
Authors: Karrowni Wassef , Zaeiter Hassan , Mansour Samy , Nassar Pierre
Published: December 2020

Atherectomy, whether rotational or orbital, is an essential and established method for treatment of calcified coronary lesions. By modifying the plaque, atherectomy lessens the risk of plaque shift and facilities stent delivery and stent expansion. Atherectomy technique is meticulous and challenging especially in tortuous and angulated coronary arteries. Herein, we describe the rare case of occurrence and the management of fracture of the tip of the crown of CSI Diamondback orbital atherectomy device during treatment of severely angulated and calcified ostial left circumflex lesion.
Utilization of Pressmud Waste as a Carrier for Enhancing Agronomic Traits of Finger Millet
Authors: Rawat Jyoti , Saxena Jyoti , Sanwal Pankaj
Published: December 2020

As India is the second‐largest producer of sugarcane in the world, a huge amount of biodegradable by‐product waste, pressmud, is produced every year, and is a promising source of nutrients. Here, an attempt is made to utilize pressmud as carrier for bioinoculants for enhancing crop productivity. The field experiments are set up on finger millet crop using Aspergillus niger (K7) as fungal inoculant and pressmud as carrier. Four treatment combinations, viz., control, K7 strain, pressmud, and K7 strain+pressmud, in soil are studied. The results indicate that the soil nutrients such as N, P, and K increase by 30–50% after the experiment. The pressmud supports up to 5 × 106 fungal spores and the inoculum is viable until the end of 6 months. Growth and yield parameters are influenced positively and result in better height and weight of plants, a higher number of fingers, and improved P uptake. The combination of A. niger (K7) and pressmud is found to be the best. Shoot and root lengths increase by 54% and 96%, respectively, at the time of harvest over control. Number of fingers and weight of grains/plant increase by 77% and 70%, respectively, at 130 days after sowing. It can be concluded that the use of pressmud with microbial inoculant may be an economically viable technology in organic farming and also in its disposal.
Cycle Class Maps and Birational Invariants
Authors: Hassett Brendan , Tschinkel Yuri
Published: December 2020

We introduce new obstructions to rationality for geometrically rational threefolds arising from the geometry of curves and their cycle maps. © 2020 Wiley Periodicals LLC
A Roadmap Towards Visible Light Mediated Electron Transfer Chemistry with Iridium(III) Complexes
Authors: Bevernaegie Robin , Wehlin Sara A. M. , Elias Benjamin , Troian‐Gautier Ludovic
Published: December 2020

Photo‐induced electron transfer chemistry between molecules is a central theme in several fields including biology, physics and chemistry. Specifically, in photoredox catalysis, greater use has been made of iridium(III) complexes as they exhibit ground‐ and excited‐state redox potentials that span a very large range. Unfortunately, most of these complexes suffer from limited visible light absorption properties. This concept article highlights recent developments in the synthesis of iridium(III) complexes with increased visible light absorption properties and their use as candidates for visible light driven redox catalysis. Fundamental tools are provided to enable the independent tuning of the HOMO and LUMO energy levels. Recent examples are given with the hope that this concept article will foster further developments of iridium(III)‐based sensitizers for visible light driven reactivity.
Spent Li‐Ion Battery Graphite Turned Into Valuable and Active Catalyst for Electrochemical Oxygen Reduction
Authors: Liivand Kerli , Kazemi Maryam , Walke Peter , Mikli Valdek , Uibu Mai , Macdonald Digby D. , Kruusenberg Ivar
Published: December 2020

Employing Li‐ion batteries (LIBs) in portable electronics has become a necessity in the modern world but, due to the short application time for any given battery (1–3 years), the quantity of spent LIBs (SLIBs) waste is becoming substantial. Herein, a novel strategy for recycling SLIB graphite and reforming it as a valuable catalyst material for electrochemical oxygen reduction reaction was proposed. SLIB graphite has been used as a precursor material for graphite oxide, which was thereafter doped with nitrogen to prepare nitrogen‐doped graphene (NG‐Bat). The prepared NG‐Bat was characterized by various physical characterization methods and the electrochemical properties of the resulting catalyst material were investigated in alkaline media. It was found that NG‐Bat prepared from SLIB had superior physical and electrochemical properties in comparison to commercial nitrogen‐doped graphene. The findings clearly demonstrate the importance of the recycling of SLIB graphite and its great potential to be re‐applied for various applications.
Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection
Authors: Rinchai Darawan , Altman Matthew C. , Konza Oceane , Hässler Signe , Martina Federica , Toufiq Mohammed , Garand Mathieu , Kabeer Basirudeen Syed Ahamed , Palucka Karolina , Mejias Asuncion , Ramilo Octavio , Bedognetti Davide , Mariotti‐Ferrandiz Encarnita , Klatzmann David , Chaussabel Damien
Published: December 2020

Biomarkers to assess the risk of developing severe respiratory syncytial virus (RSV) infection are needed. We conducted a meta‐analysis of 490 unique profiles from six public RSV blood transcriptome datasets. A repertoire of 382 well‐characterized transcriptional modules was used to define dominant host responses to RSV infection. The consolidated RSV cohort was stratified according to four traits: “interferon response” (IFN), “neutrophil‐driven inflammation” (Infl), “cell cycle” (CC), and “erythrocytes” (Ery). We identified eight prevalent blood transcriptome phenotypes, of which three Ery+ phenotypes comprised higher proportions of patients requiring intensive care. This finding confirms on a larger scale data from one of our earlier reports describing an association between an erythrocyte signature and RSV disease severity. Further contextual interpretation made it possible to associate this signature with immunosuppressive states (late stage cancer, pharmacological immunosuppression), and with a population of fetal glycophorin A+ erythroid precursors. Furthermore, we posit that this erythrocyte cell signature may be linked to a population of immunosuppressive erythroid cells previously described in the literature, and that overabundance of this cell population in RSV patients may underlie progression to severe disease. These findings outline potential priority areas for biomarker development and investigations into the immune biology of RSV infection. The approach that we developed and employed here should also permit to delineate prevalent blood transcriptome phenotypes in other settings.
Disordered eating behaviors and sexual objectification during New York fashion week: Implementation of industry policies and legislation
Authors: Rodgers Rachel F. , Ziff Sara , Lowy Alice S. , Austin S. Bryn
Published: December 2020

Objective

The working conditions of professional fashion models may place them at risk for negative outcomes including disordered eating. New policies in the United States and France, including providing private changing areas and requiring medical certificates, have been implemented to protect models from pressures to be extremely thin and sexual harassment. This study evaluated the implementation of the new policies during the week of New York Fashion Week, February 2018 (NYFW Fall'18).

Method

A sample of 76 fashion models (87% female) aged over 18 years who had participated in NYFW Fall'18 completed an online survey, reporting on behaviors and experiences occurring during NYFW Fall'18.

Results

A large proportion of respondents reported unhealthy weight control behaviors, including skipping meals (54%), intravenous drips (39%), and self‐induced vomiting (25%). Fewer than half reported being always or sometimes provided with a private changing area, with 45% reporting experiencing lack of privacy when changing. A subset (n = 15) had obtained a health certificate for events in Paris. Most health providers had assessed weight, but few assessed eating and exercise behaviors.

Discussion

Policy interventions to improve health and safety of models are not yet achieving intended goals and require continued monitoring.
Gut microbiota alteration in adolescent anorexia nervosa does not normalize with short‐term weight restoration
Authors: Schulz Nina , Belheouane Meriem , Dahmen Brigitte , Ruan Vanessa A. , Specht Hannah E. , Dempfle Astrid , Herpertz‐Dahlmann Beate , Baines John F. , Seitz Jochen
Published: December 2020

Objective

Gut microbiota are linked to metabolic function, body weight regulation, and brain and behavioral changes. Alteration of gut microbiota is repeatedly demonstrated in adults with anorexia nervosa (AN) and transplantation of stool from adult patients with AN reduces weight gain, food consumption and food efficiency in germ‐free mice. No similar data are available for adolescents, who might differ from adults due to their shorter duration of illness.

Method

Nineteen female adolescent patients with AN at admission and after short‐term weight recovery were included in a longitudinal study and compared to 20 healthy controls (HC). DNA was extracted from stool samples and subjected to 16S rRNA gene sequencing and analysis. Group comparisons, indicator genera and simper analysis were applied. Taxon abundances at admission was used to predict inpatient treatment duration.

Results

Alpha diversity is increased in patients with AN after short‐term weight recovery, while beta diversity shows clear group differences with HC before and after weight gain. A reduction in Romboutsia and taxa belonging to Enterobacteriaceae at both timepoints and an increase in taxa belonging to Lachnospiraceae at discharge are most indicative of patients. Lachnospiraceae abundance at admission helped to predict shorter inpatient treatment duration.

Discussion

This pilot study provides first evidence of gut microbiota alterations in adolescent patients with AN that do not normalize with weight gain. If verified in larger studies, the predictive power of taxa belonging to Lachnospiraceae for clinical outcome could complement known predictors at admission, inform clinicians and serve as a target for nutritional interventions.
Spider traps amphibian in northeastern Madagascar
Authors: Fulgence Thio Rosin , Martin Dominic Andreas , Kreft Holger , Ratsoavina Fanomezana Mihaja , Andrianarimisa Aristide
Published: December 2020

Predation can take unexpected turns. For instance, various invertebrate species—most commonly spiders—may prey on vertebrates. Here, we report one observation of a spider (Sparassidae, Damastes sp.) feeding on an amphibian (Hyperoliidae, Heterixalus andrakata) inside a retreat in northeastern Madagascar. To our knowledge, this is the second report of vertebrate predation by spiders in Madagascar. Three additional observations of retreats built by the same spider species show that the spiders built similar retreats and were hiding at the rear end of the retreat. The retreats were built by weaving two green leaves together which were still attached to the tree. We speculate from the observations, that the retreat serves as a targeted trap that deceives frogs seeking shelter during daytime.
Dielectric spectroscopy of red blood cells in sickle cell disease
Authors: Liu Jia , Qiang Yuhao , Du E
Published: December 2020

Hypoxia‐induced polymerization of sickle hemoglobin and the related ion diffusion across cell membrane can lead to changes in cell dielectric properties, which can potentially serve as label‐free, diagnostic biomarkers for sickle cell disease. This article presents a microfluidic‐based approach with on‐chip gas control for the impedance spectroscopy of suspended cells within the frequency range of 40 Hz to 110 MHz. A comprehensive bioimpedance of sickle cells under both normoxia and hypoxia is achieved rapidly (within ∼7 min) and is appropriated by small sample volumes (∼2.5 μL). Analysis of the sensing modeling is performed to obtain optimum conditions for dielectric spectroscopy of sickle cell suspensions and for extraction of single cell properties from the measured impedance spectra. The results of sickle cells show that upon hypoxia treatment, cell interior permittivity and conductivity increase, while cell membrane capacitance decreases. Moreover, the relative changes in cell dielectric parameters are found to be dependent on the sickle and fetal hemoglobin levels. In contrast, the changes in normal red blood cells between the hypoxia and normoxia states are unnoticeable. The results of sickle cells may serve as a reference to design dielectrophoresis‐based cell sorting and electrodeformation testing devices that require cell dielectric characteristics as input parameters. The demonstrated method for dielectric characterization of single cells from the impedance spectroscopy of cell suspensions can be potentially applied to other cell types and under varied gas conditions.
Viscoelastic particle focusing in human biofluids
Authors: Kim Bookun , Lee Sung Sik , Yoo Tae Hyeon , Kim Ju Min
Published: December 2020

Saliva and blood plasma are non‐Newtonian viscoelastic fluids that play essential roles in the transport of particulate matters (e.g., food and blood cells). However, whether the viscoelasticity of such biofluids alters the dynamics of suspended particles is still unknown. In this study, we report that under pressure‐driven microflows of both human saliva and blood plasma, spherical particles laterally migrate and form a focused stream along the channel centerline by their viscoelastic properties. We observed that the particle focusing varied among samples on the basis of sampling times/donors, thereby demonstrating that the viscoelasticity of the human biofluids can be affected by their compositions. We showed that the particle focusing, observed in bovine submaxillary mucin solutions, intensified with the increase in mucin concentration. We expect that the findings from this study will contribute to the understanding of the physiological roles of viscoelasticity of human biofluids.
Excellent electrochemical performance of LiNi0.5Co0.2Mn0.3O2 with good crystallinity and submicron primary dispersed particles
Authors: Xie Yanfang , Wu Fuzhong , Dai Xinyi , Mai Yi , Gu Yijing , Jin Huixin , Li Junqi
Published: December 2020

Nickel‐cobalt‐manganese ternary cathode materials are known as one of the most promising future cathode materials for Li‐ion batteries (LIBs) due to their high discharge capacity, environmental friendliness, and low cost. In this paper, submicron LiNi0.5Co0.2Mn0.3O2 (NCM523) primary particles with good crystallinity and dispersibility have been synthesized combine a coprecipitation method used ethanol as solvent with solid‐phase sintering technology. A feeding strategy through separate dropping of sodium carbonate and ammonia is adopted; the structure and properties of NCM523 under different pH conditions are investigated. It is found that the NCM523 synthesized at pH = 8 (NCM523‐8) exhibits a uniform particle size of about 300 nm, with good crystallinity. The NCM523‐8 exhibits an excellent high‐potential cycling performance, with an initial discharge capacity of 193.6 mAh g−1 at 0.2 C in the voltage of 3.0 to 4.5 V, and the capacity retention is 91% after 100 cycles. It also shows excellent rate performance with a reversible capacity of 130 mAh g−1 at 5 C. The superior high‐potential electrochemical performance is attributed to the improved lithium‐ion diffusion coefficient and stabilized structure by the special structural characteristics as evidenced by cyclic voltammetry, electrochemical impedance spectroscopy, and X‐ray diffraction.
Experimental investigation on gas‐liquid flow distribution in downward parallel pipes of a 660 MW ultrasupercritical CFB boiler
Authors: Xin Yafei , Niu Tiantian , Li Yinlong , Yang Dong
Published: December 2020

The arrangement of downward flowing evaporation heating surface in the furnace can effectively reduce the height of the furnace in the ultrasupercritical circulating fluidized bed boiler. According to the structural parameters of 660 MW ultrasupercritical circulating fluidized bed boiler, the scaled experimental system was established on the basis of the similarity criterion. The distribution of the gas–liquid two‐phase flow in the parallel branch pipes of the downward and the upward water‐cooled wing‐wall was studied under the rated loads of 25%, 50%, and 70% THA. The void fraction distribution, flow distribution of each phase, and dryness distribution in each branch pipe of the downcomers and the risers of the water‐cooled wing‐wall were measured via the quick‐closing valve method and the split‐phase measurement method. In the downward water‐cooled wing‐wall, both the nonuniform coefficient of void fraction and dryness in each branch pipe decreased with the increase in dryness in the inlet header. Under the same average dryness, the nonuniform coefficient of the void fraction increased with the increase in load. In the upward water‐cooled wing‐wall, under the same load, the uniformity of flow distribution was improved as the dryness increases. Under the same dryness condition, as the boiler load increases, the deviation coefficient of each phase distribution between the parallel pipes increased and the unevenness increased. In the study of flow and heat transfer characteristics of two‐phase flow, the void fraction α is a very important intermediate calculation parameter. The correlation formula of the cross‐sectional void fraction in the downward water‐cooled wing‐wall was fitted, and the calculation result was better compared with drift‐flux model, with an error of −6% to 6%.
Dietary intake of carbohydrates in pregnant women with type 1 diabetes—A narrative review
Authors: Roskjær Ann B. , Ásbjörnsdóttir Björg , Tetens Inge , Larnkjær Anni , Mølgaard Christian , Mathiesen Elisabeth R.
Published: December 2020

In pregnant women with type 1 diabetes, a low but sufficient, intake of carbohydrates is important to aim for near normal glycemic control. However, knowledge about the carbohydrate intake in this group is limited. To assess the average quantity and quality of carbohydrate intake in pregnant women with type 1diabetes compared to healthy pregnant women and current dietary reference intakes. A narrative literature search was performed in PubMed, Embase, and Cochrane Library and by using a snow‐ball search technique to identify papers published on studies conducted in industrialized countries within the last 20 years. Intakes of carbohydrate were assessed qualitatively in relation to the Dietary Reference Intakes recommended by the American Diabetes Association and quantitatively as mean intake of dietary fiber. Five observational studies including 810 pregnant women with type 1 diabetes and 15 observational studies with a total of 118,246 healthy pregnant women were identified. The mean total carbohydrate intake was within the Acceptable Macronutrient Distribution Range (45%–64% of energy intake) in both groups. In pregnant women with type 1 diabetes, the average total intake was 218 ± 19 g/day, which was 20% (53 g/day) lower than in healthy pregnant women. Mean intake of dietary fiber in women with diabetes was lower than the recommended adequate intake for healthy women. With the limitations of pronounced heterogeneity across the included studies, pregnant women with type 1 diabetes reported a mean total carbohydrate intake, which was lower than in healthy pregnant women but still within the recommended range.
Novel factor in olfactory ensheathing cell‐astrocyte crosstalk: Anti‐inflammatory protein α‐crystallin B
Authors: Saglam Aybike , Calof Anne L. , Wray Susan
Published: December 2020

Astrocytes are key players in CNS neuroinflammation and neuroregeneration that may help or hinder recovery, depending on the context of the injury. Although pro‐inflammatory factors that promote astrocyte‐mediated neurotoxicity have been shown to be secreted by reactive microglia, anti‐inflammatory factors that suppress astrocyte activation are not well‐characterized. Olfactory ensheathing cells (OECs), glial cells that wrap axons of olfactory sensory neurons, have been shown to moderate astrocyte reactivity, creating an environment conducive to regeneration. Similarly, astrocytes cultured in medium conditioned by cultured OECs (OEC‐CM) show reduced nuclear translocation of nuclear factor kappa‐B (NFκB), a pro‐inflammatory protein that induces neurotoxic reactivity in astrocytes. In this study, we screened primary and immortalized OEC lines to identify these factors and discovered that Alpha B‐crystallin (CryAB), an anti‐inflammatory protein, is secreted by OECs via exosomes, coordinating an intercellular immune response. Our results showed that: (a) OEC exosomes block nuclear NFκB translocation in astrocytes while exosomes from CryAB‐null OECs could not; (b) OEC exosomes could be taken up by astrocytes, and (c) CryAB treatment suppressed neurotoxicity‐associated astrocyte transcripts. Our results indicate CryAB, as well as other factors secreted by OECs, are potential agents that can ameliorate, or even reverse, the growth‐inhibitory environment created by neurotoxic reactive astrocytes following CNS injuries.
Reduced Clot Stability by Thromboelastography as a Potential Indicator of Procedure-Related Bleeding in Decompensated Cirrhosis
Authors: Zanetto Alberto , Rinder Henry M. , Senzolo Marco , Simioni Paolo , Garcia-Tsao Guadalupe
Published: December 2020

In patients with decompensated cirrhosis, procedure-related bleeding is a potentially lethal complication. Routine coagulation tests such as international normalized ratio and platelet count do not predict bleeding risk. We investigated whether thromboelastography (TEG) can identify patients with cirrhosis who are at risk of procedure-related bleeding. As a part of a prospective study on hemostasis in decompensated cirrhosis, patients had TEG performed on admission and were followed prospectively during hospitalization for the development of procedure-related bleeding. Eighty patients with cirrhosis were included. Among the 72 who had procedures performed, 7 had procedure-related bleeding, which was major in three cases (two following paracentesis and one following thoracentesis). Conventional coagulation tests were comparable between bleeding and nonbleeding patients, whereas TEG parameters of k-time (4.5 minutes vs. 2.2 minutes; P = 0.02), α-angle (34° vs. 59°; P = 0.003), and maximum amplitude (37 mm vs. 50 mm; P = 0.004) were significantly different (all indicative of hypocoagulability). TEG maximum amplitude (MA), a marker of overall clot stability, accurately discriminated between patients who had major, life-threatening bleeding (all with MA < 30 mm) and those who had mild or no bleeding (all with MA > 30 mm), whereas a platelet count < 50 × 109/L could not discriminate between bleeding (minor or major) and nonbleeding patients. Conclusion: In a prospective cohort of hospitalized patients with decompensated cirrhosis, TEG parameters associated with hypocoagulability appeared to predict procedure-related bleeding, particularly a TEG MA < 30 mm. If results are validated in a larger cohort, this could be a threshold to identify patients with decompensated cirrhosis at higher risk for procedure-related bleeding, in whom to consider preprocedural prophylaxis.
Genetic polymorphisms associated with polycystic ovary syndrome among Iranian women
Authors: Jamshidi Mohammad , Mohammadi Pour Somayeh , Bahadoram Mohammad , Mahmoudian‐Sani Mohammad‐Reza , Saeedi Boroujeni Ali
Published: December 2020

Polycystic ovary syndrome (PCOS) involves abnormalities in ovarian, reproductive, and metabolic systems. Genetic polymorphisms associated with individual differences and variations might be related to complex disorders with unknown causes, including PCOS. Several leading genetic markers with known cellular functions have been identified among Iranian women presenting with PCOS. In particular, the existing evidence shows a significant relationship between PCOS and the following genetic polymorphisms: rs2275913 (interleukin‐17A), rs9927163 (interleukin‐32), Pro12Ala (peroxisome proliferator‐activated receptor‐γ), rs17173608 (chemerin), rs2236242 (vaspin), ApaI (vitamin D receptor), and rs7895833 (sirtuin 1). In addition, a higher risk of PCOS is associated with the rs2910164 (microRNA 146a), rs2241766 (adiponectin), –34 T/C (cytochrome 17), and rs1800682 (Fas) polymorphisms. Furthermore, protective effects against PCOS have been reported for the A4223C polymorphism of adenosine deaminase 1. Overall, the available data indicate that Iranian women with PCOS have a higher prevalence of polymorphisms in inflammation‐ and metabolism‐related genes, but not in insulin‐related genes. More extensive studies are needed to identify the ethnicity‐related genetic associations in PCOS.
Successful surgical resection and reconstruction of scrotal elephantiasis
Authors: Hattori Yuto , Hayata Naoki , Nakamura Kenji , Takahashi Takeshi , Mitsumori Kenji , Ohnishi Hiroyuki
Published: December 2020

Introduction

An enlarged scrotum due to scrotal elephantiasis results in a poor quality of life. This condition is uncommon and challenging to manage for most urologists. We report a case of scrotal elephantiasis treated with resection and scrotal reconstruction.

Case presentation

A 57‐year‐old man was referred to our hospital with a 6‐year history of scrotal swelling. The scrotum was 20 cm in diameter, stiff, and thick. He was diagnosed with chronic scrotal lymphedema and underwent scrotal resection. The skin and subcutaneous tissues of the scrotum were excised, and the suprapubic skin, which was stretched by the enlarged scrotum, was used for the scrotal reconstruction. The penis was pulled out from this hole in the skin.

Conclusion

Utilizing suprapubic skin flap for scrotal reconstruction is an effective treatment for scrotal elephantiasis that can result in functionally and cosmetically successful outcomes.
LncRNA RAD51‐AS1/miR‐29b/c‐3p/NDRG2 crosstalk repressed proliferation, invasion and glycolysis of colorectal cancer
Authors: Li Caiping , Wang Pengcheng , Du Jiabin , Chen Junxing , Liu Weinan , Ye Kai
Published: December 2020

LncRNAs are recently increasingly emerging as molecules that take its part in human carcinogenesis. A large body of literature has identified the functional roles of lncRNAs in the pathophysiology of CRC. The current study was intended to provide new ideas and perspectives for the functional role of lncRNA RAD51‐AS1 in regulating CRC progression. Herein, a survey of RAD51‐AS1 expression profile in The Cancer Genome Atlas (TCGA)‐colon adenocarcinoma (COAD) dataset revealed that RAD51‐AS1 was downregulated in COAD specimens. Consistently, RAD51‐AS1 expression was observed to be lower in CRC cell lines compared with normal cell line (NCM460). In the meanwhile, both the levels of miR‐29b‐3p and miR‐29c‐3p were prominently elevated in CRC cells. Functionally, administration of RAD51‐AS1 refrained growth, invasion and migration of CRC cells. Additionally, accumulation of RAD51‐AS1 hampered glucose consumption and lactate production, as well as the restraint of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) levels. More important, RAD51‐AS1 functioned as a competing endogenous RNA (ceRNA) for sponging miR‐29b‐3p and miR‐29c‐3p, leading to enhancement of their common target N‐myc downstream‐regulated gene 2 (NDRG2). Mechanistically, the delivery of miR‐29b/c‐3p mimics or ablation of NDRG2 effectively blunted the salutary effects of RAD51‐AS1 on CRC cell behaviors. Moreover, augmentation of RAD51‐AS1 inhibited the tumorigenesis of CRC cells in vivo. Collectively, these findings provide comprehensive evidence that RAD51‐AS1 repressed cell proliferation, migration, invasion and glycolysis process, ultimately contributing to the progression of CRC by repressing the miR‐29b/c‐3p/NDRG2 signaling axis, insinuating the putative potential of RAD51‐AS1/miR‐29b/c‐3p/NDRG2 interaction network in unraveling CRC pathology and hopefully contributed to the treatment of CRC patients.
Talking to policy makers about genetic counseling: A personal reflection
Authors: Bishop Michelle
Published: December 2020

Many genetic counselors will, at some point in their career, work alongside policy makers either at a local, regional, or national level. This commentary reflects my personal experience of working with policy makers in the National Health Service (NHS) in England. It outlines the challenges I faced and the lessons that I learnt along the way. This article is not meant to be a ‘how to guide’, rather to provide some practical tips to those new to working in policy and strategy. Throughout this commentary, I have compared working with policy makers with other areas that I have worked in, including genetic counseling, and shown how I have drawn on different skills to support this new area of my work. I hope that others will be able to reflect on my experience and see how they can also use their own attributes in similar situations.
Robotic vs open distal pancreatectomy: A multi‐institutional matched comparison analysis
Authors: Magistri Paolo , Boggi Ugo , Esposito Alessandro , Carrano Francesco Maria , Pesi Benedetta , Ballarin Roberto , De Pastena Matteo , Menonna Francesca , Moraldi Luca , Melis Marcovalerio , Coratti Andrea , Newman Elliot , Napoli Niccolò , Ramera Marco , Di Benedetto Fabrizio
Published: December 2020

Background

Pancreatic surgery is still a challenge even in high‐volume centers. Clinically relevant postoperative pancreatic fistula (CR‐POPF) represents the greatest contributor to major morbidity and mortality, especially following pancreatic distal resection. In this study, we compared robotic distal pancreatectomy (RDP) to open distal pancreatectomy (ODP) in terms of CR‐POPF development and analyzed oncologic efficacy of RDP in the subgroup of patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

We collected data from five high‐volume centers for pancreatic surgery and performed a matched comparison analysis to compare short and long‐term outcomes after ODP or RDP. Patients were matched with a 2:1 ratio according to age, ASA (American Society of Anesthesiologists) score, body mass index (BMI), final pathology, and TNM (Tumour, Node, Metastasis) staging system VIII ed.

Results

Two hundred and forty‐six patients who underwent 82 RDPs and 164 ODPs were included. No differences were found in the incidence of CR‐POPF. In the PDAC group, median DFS and OS were 10.8 months and 14.8 months in the ODP group and 10.4 months and 15 months in the RDP group, respectively.

Conclusions

Robotic distal pancreatectomy is a safe surgical strategy for PDAC and incidence of CR‐POPF is equivalent between RDP and ODP. RDP should be considered equivalent to ODP in terms of oncological efficacy when performed in high‐volume and proficient centers.
MRI in Children With Pyriform Sinus Fistula
Authors: Han Zhonglong , Tai Jun , Gao Jun , Wang Shengcai , Yu Tong , Peng Yun , Ni Xin
Published: December 2020

Background

A variety of imaging modalities have been described for the diagnosis of congenital pyriform sinus fistula (CPSF). To date, there have been few MRI reports.

Purpose

To evaluate MRI findings of CPSF and interobserver reliability.

Study Type

Retrospective.

Population

In all, 115 patients aged 23 days to 15.4 years at operation.

Field Strength/Sequence

3.0T/axial T1‐weighted image (T1WI)‐SPIR, axialT2WI, axialT2WI‐STIR, coronalT2WI‐SPIR, diffusion‐weighted imaging (DWI), axial and coronal gadolinium‐enhancedT1WI‐SPIR.

Assessment

For each patient, the medical records, including demographics, clinical manifestations, and MRI findings were reviewed. All the MRI studies were interpreted by three radiologists independently.

Statistical Test

Kendall's W test was made to determine the interobserver reliability of three reviewers for MRI findings.

Results

CPSF occurred on the left side in 104 (90.4%) patients and on the right side in 11 (9.6%) patients. The male‐to‐female ratio was 59:56. The age at first episode varied from birth to 12.3 years. There was one neonate patient, who presented with a unilocular cystic mass in the left neck. A tunnel‐like lesion between the pyriform fossa and the upper pole of the thyroid gland, T2high signal behind the cricothyroid joint, thyroid gland involvement, deep neck abscesses or masses were noted in 46 (40%), 93 (80.9%), 96 (83.5%), and 36 (31.3%) patients, respectively. There was excellent interobserver reliability for all the MRI findings, ranging from 0.84 to 1.00.

Data Conclusion

The sinus tract presenting with a tunnel‐like lesion goes behind the cricothyroid joint in most cases. For patients presenting with acute suppurative thyroiditis (AST) or neck infection with thyroid gland involvement, the presence of T2high signal behind the cricothyroid joint highly suggests the diagnosis of CPSF. MRI is a reliable method for the diagnosis of CPSF.

Level of Evidence

4

Technical Efficacy Stage

2
Non‐target environmental analysis by liquid chromatography/high‐resolution mass spectrometry with a product ion and neutral loss database
Authors: Suzuki Shigeru , Hasegawa Atsuko , Uebori Michiko , Shinomiya Miho , Yoshida Yasuko , Ookubo Kaori , Takino Masahiko , Hasegawa Hitomi , Takazawa Mari , Takemine Shusuke
Published: December 2020

Despite the increasing detection of emerging substances in the environment, the identity of most are left unknown due to the lack of efficient identification methods. We developed a non‐target analysis method for identifying unknown substances in the environment by liquid chromatography/high‐resolution mass spectrometry (LC/HRMS) with a product ion and neutral loss database (PNDB). The present analysis describes an elucidation method with elemental compositions of the molecules, product ions, and corresponding neutral losses of the unknown substance: (1) with the molecular formula, possible molecular structures are retrieved from two chemical structure databases (PubChem and ChemSpider); then (2) with the elemental compositions of product ions and neutral losses, possible partial structures are retrieved from the PNDB; and finally, (3) molecular structures that match the possible partial structures are listed in order of number of hits. A molecular structure with a higher number of hits is more similar to the structure of the analyzed substance. The performance of the non‐target method was evaluated by simulated analysis of 150 LC/HRMS spectra registered in MassBank. First, all substances of the same mass data (41/41) and 68% (39/57) of the mass data of the same substances not registered in the PNDB were elucidated. It was demonstrated that 14% (7/52) and 31% (16/52) of the substances with no mass spectral data registered in the PNDB were obtained at the first and within the fifth place, respectively. Owing to the fact that 10 of the total hits occurred in product ions and neutral losses, almost 50% of the substances evaluated with this method were placed at the top 4 positions in the similarity ranking. Importantly, the proposed method is effective for analyzing mass spectral data that has not been registered in the PNDB and thus is expected to be used for a variety of non‐target analyses.
Administration of intravenous immunoglobulin in the treatment of COVID‐19: A review of available evidence
Authors: Moradimajd Parisa , Samaee Hamidreza , Sedigh‐Maroufi Shahnam , Kourosh‐Aami Masoumeh , Mohsenzadegan Monireh
Published: December 2020

Since December 31, 2019, unknown causes of pneumonia have been reported in Wuhan, China. This special pneumonia associated with a novel coronavirus was named 2019‐nCoV by the World Health Organization (WHO) in January 2020. From the beginning of this infectious disease, clinicians and researchers have been endeavoring to discover an effective and suitable treatment for affected patients. To date, there is no definitive and specific treatments for coronavirus disease‐19 (COVID‐19) infection while drugs introduced are still in the clinical trial phase. Intravenous immune globulin (IVIG) is a biological product prepared from the serum and an optional treatment for patients with antibody deficiencies. In many countries, much attention has been paid to the use of IVIG in the treatment of patients with COVID‐19. Due to the therapeutic importance of IVIG in virus infections, in the current study, we reviewed the possible effect of IVIG in viral infections and potential evidence of IVIG therapy in patients with COVID‐19 virus.
Improvement in quality of life and cardiac function after catheter ablation for asymptomatic persistent atrial fibrillation
Authors: Onishi Naoaki , Kyo Shokan , Oi Maki , Jinnai Toshikazu , Kuroda Maiko , Shimizu Yukiko , Imamura Sari , Harita Takeshi , Nishiuchi Suguru , Hanazawa Koji , Tamura Toshihiro , Izumi Chisato , Nakagawa Yoshihisa , Kaitani Kazuaki
Published: December 2020

Background

Catheter ablation (CA) for atrial fibrillation (AF) is widely performed. However, the indication for CA in patients with asymptomatic persistent AF is still controversial.

Methods

Among 259 consecutive patients who were hospitalized for initial CA of AF, a total of 45 patients who had asymptomatic persistent AF were retrospectively analyzed. Quality of life (QOL) before and 1 year after CA was evaluated, and changes in the cardiac function over 5 years after CA were also examined. QOL was assessed using the AF QOL questionnaire (AFQLQ) developed by the Japanese Heart Rhythm Society. In addition, cardiac function was assessed by measuring the plasma B‐type natriuretic peptide (BNP) level, left ventricular ejection fraction (LVEF), left atrial diameter (LAD) with transthoracic echocardiogram, and left atrial (LA) volume with computed tomography (CT).

Results

The AFQLQ significantly improved after CA in terms of “symptom frequency” and “activity limits and mental anxiety.” The plasma BNP level, LVEF, and LAD significantly improved in the first 3 months after the first CA, with no significant changes thereafter (from 149.0 pg/dL [95% confidence intervals {CI}, 114.5‐183.5 pg/dL] to 49.8 pg/dL [95% CI, 26.5‐70.1], P < .0001; from 60.8% [95% CI, 58.1%–63.6%] to 65.0% [95% CI, 62.6‐67.4], P = .001; and from 41.3 mm [95% CI, 39.7‐42.9] to 36.8 [95% CI, 34.5‐39.1 mm], P < .0001, respectively). LA volume revealed LA reverse remodeling after CA.

Conclusion

Improvement in the QOL and cardiac function after CA of asymptomatic persistent AF was revealed. Asymptomatic persistent AF should be appropriately treated by CA.
The influence of atmospheric circulation patterns during large snowfall events in New Zealand's Southern Alps
Authors: Porhemmat Rasool , Purdie Heather , Zawar‐Reza Peyman , Zammit Christian , Kerr Tim
Published: December 2020

Large snowfall events contribute significantly to total annual snow accumulation across the maritime Southern Alps. However, the knowledge about atmospheric circulation patterns associated with large snowfall events over the New Zealand Southern Alps is very limited. Daily snow observation data from three automatic weather stations and ERA‐Interim reanalysis data were used to investigate the relationship between atmospheric forcing and large snowfall events across the Southern Alps. To do so, analysis of composite anomaly maps during large snowfall events were carried out to identify the common features of the days with heavy snow accumulation. Large snowfall across the Southern Alps are mainly associated with strong negative anomalies of sea level pressure (SLP) located over the southwest of New Zealand's South Island. These conditions are concurrent with negative anomalies of geopotential heights at 500 (Z500) located in the centre of low‐pressure systems. However, over New Zealand, days leading to large snowfall events experience positive anomalies of Z500 showing a relatively warm environment during such events in the maritime Southern Alps. Positive anomalies of low‐tropospheric temperatures (850 and 1,000 hPa) over the Tasman Sea and across the Southern Alps, strong values of integrated vapour transport (IVT) as well as high frequency of local synoptic patterns associated with troughing regimes (~78%) during large snowfall events provide more evidence of the important contribution of warm air flows.
Comparison of Energy Expenditure in Mechanically Ventilated Septic Shock Patients in Acute and Recovery Periods via Indirect Calorimetry
Authors: Israfilov Elmir , Kir Seher
Published: December 2020

Background

Nutrition in intensive care units (ICUs) affects morbidity and mortality. We aimed to evaluate the energy expenditure of mechanically ventilated patients in early and late septic shock periods.

Methods

This study retrospectively evaluated 28 mechanically ventilated septic shock patients (11 female/17 male) in a medical ICU. Indirect calorimetry (IC) measurement was performed for 24 hours during the acute and recovery periods of septic shock. The energy values calculated by Harris–Benedict equation (predicted resting energy expenditure [PREE]), measured by IC (measured resting energy expenditure [MREE]), and given to each patient were obtained in the acute and recovery periods.

Results

The mean age was 67.46 ± 14.92 (36–91) years. The MREE was 2741.1 ± 706.3 kcal/d (38.61 ± 11.44 kcal/kg/d) and 2332.8 ± 426.6 kcal/d (32.65 ± 7.8 kcal/kg/d) in the acute and recovery periods, respectively, and showed significant differences (P = 0.001). The patients’ energy intake was 1152.7 ± 207.1 kcal/d and 1542.7 ± 433.3 kcal/d in the acute and recovery periods, respectively. A significant difference existed between energy intake and MREE during the acute and recovery periods (P < 0.001 for both).

Conclusion

Our findings showed that energy expenditure increases in septic shock. Significant differences existed between MREE, PREE, and energy intake, which were not correlated. The MREE was higher in the acute period. Despite the increasing energy requirement, the PREE and energy intake were well below MREE. For better clinical outcomes, each patient's energy expenditure must be closely monitored and evaluated using intermittent IC measurements.
Effects of vegetation restoration on accumulation and translocation of heavy metals in post‐mining areas
Authors: Xu Shanshan , Zhao Qinghe , Qin Chengzhe , Qin Mingzhou , Lee Jay , Li Cangyu , Li Yanyan , Yang Jiaxin
Published: December 2020

Vegetation restoration has been recognized as an effective ecological measure to mitigate soil heavy metal contamination in open‐pit mining areas. However, little is known about the processes of accumulation and translocation of heavy metals in naturally restored soil–plant systems in these areas. In this study, soil and plant samples were collected from three natural restoration sites of different post‐mining ages (2, 7, and 15 years) to investigate the concentration, accumulation, and translocation of heavy metals in plant tissues (roots, stems, and leaves) of two different plant life forms (trees and shrubs). The results showed that heavy metals occurred at different concentrations in different tissues; and that site age significantly affected the concentration of metals, with higher concentration in older sites. Similarly, the accumulation of metals from soil to roots and the translocation from roots to stems were greater in older sites. We combined redundancy analysis, correlation analysis and multiple regression analysis to determine the effect of environmental factors on accumulation and translocation. Results showed that plant life form took the largest weight for accumulation of Pb, Ni, Cd, and Cr, and for translocation of Ni, Cu, and Zn. Site age made the highest contribution to accumulation of As, and to translocation of Hg and Cd. The accumulation of Hg and translocation of Pb, As, and Cr were most affected by total phosphorus. Soil pH was the major contributor to accumulation of Cu and Zn. These findings could provide some reference for post‐mining soil remediation, particularly for gold mines.
Combining Model‐Based Clinical Trial Simulation, Pharmacoeconomics, and Value of Information to Optimize Trial Design
Authors: Hill‐McManus Daniel , Hughes Dyfrig A.
Published: December 2020

The Bayesian decision‐analytic approach to trial design uses prior distributions for treatment effects, updated with likelihoods for proposed trial data. Prior distributions for treatment effects based on previous trial results risks sample selection bias and difficulties when a proposed trial differs in terms of patient characteristics, medication adherence, or treatment doses and regimens. The aim of this study was to demonstrate the utility of using pharmacometric‐based clinical trial simulation (CTS) to generate prior distributions for use in Bayesian decision‐theoretic trial design. The methods consisted of four principal stages: a CTS to predict the distribution of treatment response for a range of trial designs; Bayesian updating for a proposed sample size; a pharmacoeconomic model to represent the perspective of a reimbursement authority in which price is contingent on trial outcome; and a model of the pharmaceutical company return on investment linking drug prices to sales revenue. We used a case study of febuxostat versus allopurinol for the treatment of hyperuricemia in patients with gout. Trial design scenarios studied included alternative treatment doses, inclusion criteria, input uncertainty, and sample size. Optimal trial sample sizes varied depending on the uncertainty of model inputs, trial inclusion criteria, and treatment doses. This interdisciplinary framework for trial design and sample size calculation may have value in supporting decisions during later phases of drug development and in identifying costly sources of uncertainty, and thus inform future research and development strategies.