bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of murine steatohepatitis models identifies a dietary intervention with robust fibrosis, ductular reaction, and rapid progression to cirrhosis and cancer
Authors: Wei Guangyan , An Ping , Vaid Kahini A. , Nasser Imad , Huang Pinzhu , Tan Li , Zhao Shuangshuang , Schuppan Detlef , Popov Yury V.
Published: October 2019

Progressive fibrosis, functional liver failure, and cancer are the central liver-related outcomes of nonalcoholic steatohepatitis (NASH) but notoriously difficult to achieve in mouse models. We performed a direct, quantitative comparison of hepatic fibrosis progression in well-defined methionine- and choline-deficient (MCD) and choline-deficient, amino-acid defined (CDAA) diets with increasing fat content (10–60% by calories) in C57Bl/6J and BALB/cAnNCrl mice. In C57Bl/6J mice, MCD feeding resulted in moderate fibrosis at week 8 (up to twofold increase in total hepatic collagen content) and progressive weight loss irrespective of dietary fat. In contrast, CDAA-fed mice did not lose weight and developed progressive fibrosis starting from week 4. High dietary fat in the CDAA diet model induced the lipid metabolism genes for sterol regulatory element-binding protein and stearoyl-CoA desaturase-2 and increased ductular reaction and fibrosis in a dose-dependent manner. Longitudinal analysis of CDAA with 60% fat (HF-CDAA) feeding revealed pronounced ductular reaction and perisinusoidal bridging fibrosis, with a sevenfold increase of hepatic collagen at week 12, which showed limited spontaneous reversibility. At 24 wk, HF-CDAA mice developed signs of cirrhosis with pan-lobular “chicken wire” fibrosis, 10-fold hydroxyproline increase, regenerative nodules, portal hypertension and elevated serum bilirubin and ammonia levels; 80% of mice (8/10) developed multiple glypican-3- and/or glutamine synthetase-positive hepatocellular carcinomas (HCC). High-fat (60%) supplementation of MCD in C57Bl/6J or feeding the HF-CDAA diet fibrosis-prone BALB/cAnNCrl strain failed to result in increased fibrosis. In conclusion, HF-CDAA feeding in C57Bl/6J mice was identified as an optimal model of steatohepatitis with robust fibrosis and ductular proliferations that progress to cirrhosis and HCC within 24 wk. This robust model will aid the testing of interventions and drugs for severe NASH.

NEW & NOTEWORTHY Via quantitative comparison of several dietary models, we report HF-CDAA feeding in C57Bl/6 mice as an excellent model recapitulating several key aspects of fibrotic NASH: 1) robust, poorly reversible liver fibrosis, 2) prominent ductular reaction, and 3) progression to cirrhosis, portal hypertension, and liver cancer within 24 wk. High fat dose-dependently activates SREBP2/SCD2 genes and drives liver fibrosis in e HF-CDAA model. These features qualify the model as a robust and practical tool to study mechanisms and novel treatments addressing severe human NASH.
TRPV4 blockade reduces voiding frequency, ATP release, and pelvic sensitivity in mice with chronic urothelial overexpression of NGF
Authors: Girard Beatrice M. , Campbell Susan E. , Perkins Megan , Hsiang Harrison , Tooke Katharine , Drescher Carolyn , Hennig Grant W. , Heppner Thomas J. , Nelson Mark T. , Vizzard Margaret A.
Published: October 2019

Transient receptor potential vanilloid family member 4 (TRPV4) transcript and protein expression increased in the urinary bladder and lumbosacral dorsal root ganglia of transgenic mice with chronic urothelial overexpression of nerve growth factor (NGF-OE). We evaluated the functional role of TRPV4 in bladder function with open-outlet cystometry, void spot assays, and natural voiding (Urovoid) assays with the TRPV4 antagonist HC-067047 (1 μM) or vehicle in NGF-OE and littermate wild-type (WT) mice. Blockade of TRPV4 at the level of the urinary bladder significantly ( P ≤ 0.01) increased the intercontraction interval (2.2-fold) and void volume (2.6-fold) and decreased nonvoiding contractions (3.0-fold) in NGF-OE mice, with lesser effects (1.3-fold increase in the intercontraction interval and 1.3-fold increase in the void volume) in WT mice. Similar effects of TRPV4 blockade on bladder function in NGF-OE mice were demonstrated with natural voiding assays. Intravesical administration of HC-067047 (1 µM) significantly ( P ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in littermate WT mice. Blockade of urinary bladder TRPV4 or intravesical infusion of brefeldin A significantly ( P ≤ 0.01) reduced (2-fold) luminal ATP release from the urinary bladder in NGF-OE and littermate WT mice. The results of the present study suggest that TRPV4 contributes to luminal ATP release from the urinary bladder and increased voiding frequency and pelvic sensitivity in NGF-OE mice.
Differential expression of parietal epithelial cell and podocyte extracellular matrix proteins in focal segmental glomerulosclerosis and diabetic nephropathy
Authors: Chan Gek Cher , Eng Diana G. , Miner Jeffrey H. , Alpers Charles E. , Hudkins Kelly , Chang Anthony , Pippin Jeffrey W. , Shankland Stuart J.
Published: October 2019

In healthy glomeruli, parietal epithelial cell (PEC)-derived extracellular matrix (ECM) proteins include laminin-β1, perlecan, and collagen type IV-α2and podocyte-specific ECM proteins include laminin-β2, agrin, and collagen type IV-α4. This study aimed to define individual ECM protein isoform expression by PECs in both experimental and human focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN) and to determine if changes were CD44 dependent. In experimental FSGS induced with a cytotoxic podocyte antibody and in the BTBR ob/ob mouse model of DN, PEC-derived protein staining was significantly increased in PECs. Dual staining also showed de novo expression of the podocyte-specific ECM proteins laminin-β2and agrin in PECs. Similar findings were observed in biopsies from patients with FSGS and DN. Increases in individual ECM proteins colocalized with CD44 in PECs in disease. To determine the role of CD44, FSGS was induced in CD44−/−and CD44+/+mice. PEC staining for perlecan, collagen type IV-α2, laminin-β2, and agrin were significantly lower in diseased CD44−/−mice compared with diseased CD44+/+mice. These results show that in experimental and human FSGS and DN, PECs typically in an activated state, produce both PEC-derived and podocyte-specific ECM protein isoforms, and that the majority of these changes were dependent on CD44.
Knockout ofP2rx7purinergic receptor attenuates cyst growth in a rat model of ARPKD
Authors: Arkhipov Sergey N. , Potter D’Anna L. , Geurts Aron M. , Pavlov Tengis S.
Published: October 2019

The severity of polycystic kidney diseases (PKD) depends on the counterbalancing of genetic predisposition and environmental factors exerting permissive or protective influence on cyst development. One poorly characterized phenomenon in the cystic epithelium is abnormal purinergic signaling. Earlier experimental studies revealed the high importance of the ionotropic P2X receptors (particularly, P2X7) in the pathophysiology of the cyst wall. To study mechanisms of P2X7 involvement in cyst growth and aspects of targeting these receptors in PKD treatment we performed a CRISPR/SpCas9-mediated global knockout of the P2rx7 gene in PCK rats, a model of autosomal recessive PKD (ARPKD). A single base insertion in exon 2 of the P2rx7 gene in the renal tissues of homozygous mutant animals leads to lack of P2X7 protein that did not affect their viability or renal excretory function. However, PCK. P2rx7 rats demonstrated slower cyst growth (but not formation of new cysts) compared with heterozygous and PCK. P2rx7+littermates. P2X7 receptors are known to activate pannexin-1, a plasma channel capable of releasing ATP, and we found here that pannexin-1 expression in the cystic epithelium is significantly higher than in nondilated tubules. P2X7 deficiency reduces renal pannexin-1 protein expression and daily urinary ATP excretion. Patch-clamp analysis revealed that lack of P2X7 increases epithelial sodium channel activity in renal tissues and restores impaired channel activity in cysts. Interpretation of our current data in the context of earlier studies strongly suggests that P2X7 contributes to cyst growth by increasing pannexin-1-dependent pathogenic ATP release into the lumen and reduction of sodium reabsorption across the cyst walls.
Sevoflurane Impairs Short-Term Memory by Affecting PSD-95 and AMPA Receptor in the Hippocampus of a Mouse Model
Authors: Jiao Yuan , Fan Hongwu , Wang Kexin , Lu Shan
Published: October 2019

Objective. To explore the effects of sevoflurane on the latency and error times of the passive avoidance and levels of PSD-95 and AMPA receptors in the hippocampus. We evaluated the effects of sevoflurane on short-term memory in adult mice and explored the possible mechanism. Methods. 144 Kunming mice (2-3 months, 30-35 g) were randomly divided into two groups A (n=64) and B (n=80) and received the dark-avoidance (DA) and step-down avoidance (SA) tests, respectively. The groups DA and SA were further divided into control (inhaled 40% O2 2 h) and sevoflurane (3.3% sevoflurane and 40% O2 2 h) subgroups. Before inhalation intervention, all mice were trained to be familiar with the Morris water maze (MWM). According to the test points of behavioral indicators, 8 mice were randomly selected from each subgroup at point 12 h (T1), 24 h (T2), 48 h (T3), and 72 h (T4) after inhalation intervention. The step-through latency and error times were measured in 5 min. After the behavioral test, the mice were killed and the tissues of the hippocampus were taken for hematoxylin and eosin (H&E) staining. The expression level of PSD-95 and AMPA receptors in the hippocampus was detected by immunohistochemistry and Western Blot. The changes of synaptic transmission were measured via electrophysiology analysis of hippocampal slices. Results. The mice in the control subgroups found the platform in a shorter pathway than those in the sevoflurane subgroups during an MWM test. The step-through latency of T1 and T2 in the sevoflurane subgroup was shorter than baseline time, and the error times were increased in 5 min and higher than baseline time when compared with the control subgroup (P<0.05) in the A and B groups. Compared with the control subgroup, the expression level of PSD-95 and AMPA receptors in the hippocampus was decreased at T1 and T2 in the sevoflurane subgroup (P<0.05). The nerve cells were partially swelling. Electrophysiology analysis showed that the levels of PSD-95 and AMPA receptor expression were associated with synaptic transmission. Conclusion. Sevoflurane impaired short-term memory in adult mice by inhibiting the expression of PSD-95 and AMPA receptors in the hippocampus, which led to the decrease in synaptic transmission.
HuoXueTongFu Formula Alleviates Intraperitoneal Adhesion by Regulating Macrophage Polarization and the SOCS/JAK2/STAT/PPAR-γ Signalling Pathway
Authors: Zhao Min , Bian Yao-Yao , Yang Li-Li , Chen Yan-Qi , Wang Ya-Jie , Ma Yan-Ting , Pei Yu-Qiong , Li Wen-Lin , Zeng Li
Published: October 2019

Intraperitoneal adhesion is a common complication after abdominal surgery, which seriously affects the quality of life of patients. HuoXueTongFu Formula (HXTF) plays an important role in the prevention and treatment of intraperitoneal adhesions. However, the molecular-related mechanisms are still not fully known. In this study, the model of Intrapetitoneal adhesion was established by cecum abrasion and treated with HXTF for one week. RAW264.7 cells were given LPS, IFN-γ, IL-4, HXTF-medicated serum, and PPAR-γ agonist/antagonist, respectively. Histopathology, flow cytometry, ELISA, real-time PCR, and Western blotting were used to further detect the related protein, M1/M2 polarization tendency, and PPAR-γ nuclear translocation. The deposition of collagen fibres reduced in the local area of rats after the operation with HXTF treatment. Similar to IL-4, HXTF induced a tendency for macrophages to polarize toward M2 and promoted peroxisome proliferator-activated receptor-gamma (PPAR-γ) nuclear translocation. Furthermore, the use of HXTF and PPAR-γ agonists downregulated macrophage M1 polarization-related factors IL-1, IL-6, and TNF-alpha and upregulated M2 polarization-related factors IL-4, IL-10, and TGF-beta 1. Meanwhile, the use of HXTF and PPAR-γ agonists downregulated the SOCS3/JAK2/STAT1 pathway and activated the SOCS1/STAT6/PPAR-γ pathway. These results show that HXTF may reduce intraperitoneal adhesion by inducing macrophage M2 polarization and regulating the SOCS/JAK2/STAT/PPAR-γ pathway.
Direct Fabrication of Reduced Graphene Oxide@SnO2 Hollow Nanofibers by Single-Capillary Electrospinning as Fast NO2 Gas Sensor
Authors: Wang Dong , Tang Mingcong , Sun Jianbo
Published: October 2019

Single-capillary electrospinning has been exhibited to be a simple and scalable method for fabricating nanofibers. Construction of graphene/inorganic fibers with the core-shell hollow structure using graphene as skeleton has been rarely reported. Here, we show a facile approach to prepare electrospun reduced graphene oxide@SnO2 composite nanofibers with the hollow structure. The hollow core@shell structure is formed in a single-capillary electrospinning process including sintering, which is promising for the preparation of graphene/inorganic composite nanofibers. The reduction of as-synthesized graphene is realized by stannous ion. Resulting hollow and core-shell structure enables the reduced graphene oxide@SnO2 composite nanofibers to adsorb and desorb the target gas more easily, which is promising for future applications as fast NO2 gas sensor.
Improvement of Heliciculture by Three Medicinal Plants Belonging to the Lamiaceae Family
Authors: Lemjallad Lamiaa , Chabir Rachida , Kandri Rodi Youssef , El Ghadraoui Lahssen , Ouazzani Chahdi Fouad , Errachidi Faouzi
Published: October 2019

Snails were fed with three medicinal plants belonging to the Lamiaceae family (rosemary, sage, and peppermint) in order to test their effects on those animals with high nutritive values. The media of raising were flour containing different percentages of the cited plants ranging from 1% to 9%. The feed had benefits on the raised snails depending on the plant and its percentage. Minerals in those aromatic plants, especially zinc and magnesium, had their effect on protein synthesis in snails fed with those plant percentages. Rosemary was the most profitable plant with the highest protein amount, the lowest mortality rate, and reduced microbial charge. Furthermore, it was a good regulator of the specific catalase activity which confirmed the role of the antioxidant activity of rosemary during raising snails.
Blowout Accident Impact Analysis Method for the Siting of Offshore Floating Nuclear Power Plant in Offshore Oil Fields
Authors: Lan Zhigang
Published: October 2019

Focused on the utilization of nuclear energy in offshore oil fields, the correspondence between various hazards caused by blowout accidents (including associated, secondary, and derivative hazards) and the initiating events that may lead to accidents of offshore floating nuclear power plant (OFNPP) is established. The risk source, risk characteristics, risk evolution, and risk action mode of blowout accidents in offshore oil fields are summarized and analyzed. The impacts of blowout accident in offshore oil field on OFNPP are comprehensively analyzed, including injection combustion and spilled oil combustion induced by well blowout, drifting and explosion of deflagration vapor clouds formed by well blowouts, seawater pollution caused by blowout oil spills, the toxic gas cloud caused by well blowout, and the impact of mobile fire source formed by a burning oil spill on OFNPP at sea. The preliminary analysis methods and corresponding procedures are established for the impact of blowout accidents on offshore floating nuclear power plants in offshore oil fields, and a calculation example is given in order to further illustrate the methods.
Dao Yin (a.k.a. Qigong): Origin, Development, Potential Mechanisms, and Clinical Applications
Authors: Chen Xiaorong , Cui Jiabao , Li Ru , Norton Richard , Park Joel , Kong Jian , Yeung Albert
Published: October 2019

Dao Yin is a form of exercise combining physical movements, mental focus, and breathing originated in ancient China. In this review, we introduce the history in the development and the scope of Dao Yin, the relationship between Dao Yin with Taoist culture and Qigong, and the potential mechanisms of how Dao Yin promotes health and alleviate illnesses. Empirical research studies using Dao Yin for treatment of lumbar spondylosis, peripheral musculoskeletal diseases, cervical spondylosis, heart diseases, central nervous system disorders, immunological dysfunction, and psychological disorders are detailed.
Functional Cereal Products in the Diet for Type 2 Diabetes Patients
Authors: Krawęcka Ada , Sobota Aldona , Sykut-Domańska Emilia
Published: October 2019

Type 2 diabetes has become one of the major health problems of the modern world. It is assumed that environmental factors have a significant impact on the development of the disease, and great importance is ascribed to the diet, which can be modified accordingly. The diet can exert prophylactic and therapeutic effects; changes in the diet in advanced disease can improve the quality of life of diabetic patients and minimise the risk of complications, which are the direct cause of diabetes-related death. Functional food, which has a potentially health-enhancing effect in addition to its nutritional value, has been increasingly recognised and required. Cereal products are crucial in diabetic nutrition. Their function can additionally be enhanced by fortification with compounds with proven hypoglycaemic effects. Pasta has a low glycaemic index and is a good carrier of fortifying substances; hence, it can be highly recommended in diets for diabetic patients.
Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI
Authors: Helseth Ragnhild , Shetelig Christian , Andersen Geir Øystein , Langseth Miriam Sjåstad , Limalanathan Shanmuganathan , Opstad Trine B. , Arnesen Harald , Hoffmann Pavel , Eritsland Jan , Seljeflot Ingebjørg
Published: October 2019

Background. The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. Methods and Results. In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p≤0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p<0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p≤0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p<0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p=0.012). No such observations were encountered for MPO-DNA. Conclusions. High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008)).
Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death
Authors: Kulkarni Prathamesh M. , Robinson Eric J. , Sarin Pradhan Jaya , Gartrell-Corrado Robyn D. , Rohr Bethany R. , Trager Megan H. , Geskin Larisa J. , Kluger Harriet M. , Wong Pok Fai , Acs Balazs , Rizk Emanuelle M. , Yang Chen , Mondal Manas , Moore Michael R. , Osman Iman , Phelps Robert , Horst Basil A. , Chen Zhe S. , Ferringer Tammie , Rimm David L. , Wang Jing , Saenger Yvonne M.
Published: October 2019

Purpose:

Biomarkers for disease-specific survival (DSS) in early-stage melanoma are needed to select patients for adjuvant immunotherapy and accelerate clinical trial design. We present a pathology-based computational method using a deep neural network architecture for DSS prediction.

Experimental Design:

The model was trained on 108 patients from four institutions and tested on 104 patients from Yale School of Medicine (YSM, New Haven, CT). A receiver operating characteristic (ROC) curve was generated on the basis of vote aggregation of individual image sequences, an optimized cutoff was selected, and the computational model was tested on a third independent population of 51 patients from Geisinger Health Systems (GHS).

Results:

Area under the curve (AUC) in the YSM patients was 0.905 (P < 0.0001). AUC in the GHS patients was 0.880 (P < 0.0001). Using the cutoff selected in the YSM cohort, the computational model predicted DSS in the GHS cohort based on Kaplan–Meier (KM) analysis (P < 0.0001).

Conclusions:

The novel method presented is applicable to digital images, obviating the need for sample shipment and manipulation and representing a practical advance over current genetic and IHC-based methods.
MEK Inhibitor-Associated Central Retinal Vein Occlusion Associated with Hyperhomocysteinemia and MTHFR Variants
Authors: Francis Jasmine H. , Diamond Eli L. , Chi Ping , Jaben Korey , Hyman David M. , Abramson David H.
Published: October 2019

Background: Central retinal vein occlusion (CRVO) is a visually threatening event that has rarely been observed in patients taking MEK1/2 inhibitors and that may necessitate permanent discontinuation of a potentially efficacious therapy. We investigated the clinical characteristics of CRVO in patients on mitogen-activated protein kinase kinase (MEK) inhibition to better understand their predisposing factors and clinical course. Case Series: This was a single-center, retrospective cohort study (between December 2006 and September 2018). Three of 546 patients enrolled in 46 prospective trials involving treatment with MEK inhibitors at Memorial Sloan Kettering Cancer Center were identified as having CRVO. Clinical examination and course, multimodal ophthalmic imaging, and serum laboratory results (including homocysteine levels and genetic variants of methylene tetrahydrofolate reductase [MTHFR]) were reviewed for the 3 affected patients. All 3 patients with MEK inhibitor-associated CRVO had elevated serum homocysteine and gene variants of MTHFR (1 homozygous for A1298C, 1 heterozygous for A1298C, and 1 homozygous for C677T). Following intravitreous injections of anti-VEGF and discontinuation of drug, all patients regained vision to their baseline. Discussion: MEK inhibitor-associated CRVO is a rare event which can exhibit visual recovery after drug cessation and intravitreous anti-VEGF injections. In this cohort, it was associated with hyperhomocysteinemia and genetic mutations in MTHFR, suggesting a potential role for hyperhomocysteinemia screening prior to initiation of MEK inhibitor therapy.
Symptomatic Liver Metastasis Prompting Diagnosis of Uveal Melanoma
Authors: Awh Caroline C. , Wilson Matthew W.
Published: October 2019

We report the case of a 66-year-old male with symptomatic liver metastasis as the presenting manifestation of primary uveal melanoma. Upon initial presentation to an emergency department with 2 months of abdominal pain, back pain, and unintended weight loss, a computed tomography scan demonstrated diffuse liver and bone lesions, prompting referral to a medical oncologist. He was eventually examined by an ophthalmologist, who found a lesion suspicious for uveal melanoma. This was ultimately confirmed to be the primary site of his malignant metastatic melanoma, which caused his death within 2 months of presentation.
Cooperating on Data: The Missing Element in Bringing Real Innovation to Europe’s Healthcare Systems
Authors: Horgan Denis , Bernini Chiara , Thomas Pierre P.M. , Morre Servaas A.
Published: October 2019

Europe’s growing awareness of gaps in its healthcare provision is not being matched by an increase in remedial action – despite the rich transformative potential of new approaches to data. The new availability of data offers policymakers tools that would allow Europe’s huge investments in health to be far better spent, by being properly targeted. The result would be far better health for far more Europeans. But that requires a step that most European policymakers have not been ready to take. They need to cooperate so that the data can be shared and its full value realised. This paper explores the potential and the challenges that stand in the way of mobilising health data for wider health benefits. This paper goes on to summarise the results of a survey on how different components of the healthcare sector perceive the opportunities from mobilising data effectively, and the barriers to doing so. The responses demonstrated a widespread genuine will to promote research and innovation, and its take-up, for the betterment of healthcare. There was strong appreciation of the merits of data sharing and readiness – under the right circumstances – to share personal health data for research purposes and to undergo genetic sequencing. This paper also suggests the strategic direction that should influence policy formation. The solution can be found without changing the EU treaties, which already provide an adequate base for cooperation. Properly handled, the problems facing European healthcare can be turned into major assets for Europe and make it easier for citizens to have equal access to high-quality care through the meaningful use of digital innovations.
Variants of Papillary Thyroid Carcinoma: An Algorithmic Cytomorphology-Based Approach to Cytology Specimens
Authors: Canberk Sule , Montezuma Diana , Ince Umit , Tastekin Ebru , Soares Paula , Bongiovanni Massimo , Schmitt Fernando C.
Published: October 2019

Background: Thyroid cancer accounts for 1% of cancer cases in developed countries, in which papillary thyroid carcinoma (PTC) is the most common type. There are multiple variants of PTC described to date, some of them with aggressive behavior and poor clinical outcome. These variants are well described and accepted in recent guidelines of many international societies, and the prognostic and management implications are well laid out. Due to their established clinical importance and to guide appropriate surgical management, it is now imperative in clinical practice, including cytopathology, to differentiate aggressive variants from nonaggressive ones. This review aims to describe the variants of PTC and to provide a practical algorithmic approach to facilitate the cytological diagnosis of these variants. Summary: Subtyping PTC variants on fine needle aspiration cytology (FNAC) is challenging even for the most experienced cytopathologist. To facilitate a correct subtyping on FNAC, we propose a stepwise approach that is mainly designed for conventional smear methodology. This approach requires first to stratify the lesions into oncocytic and nononcocytic features before analyzing further details in cell morphology and pattern. Key Messages: (1) Subtyping in PTC is possible on cytopathology. (2) The main aim of the cytopathologist is to differentiate aggressive from nonaggressive variants. (3) The subtyping of PTC can help in the surgical management of the patients.
An Endotracheal Plasmablastic Lymphoma
Authors: Bots Eva M.T. , Opperman Johan , Bassa Fatima , Koegelenberg Coenraad F.N.
Published: October 2019

We describe an exceptionally rare case of a male patient with newly diagnosed advanced human immunodeficiency virus (HIV) infection, who presented with a plasmablastic lymphoma involving the right maxillary alveolar ridge with associated cervical lymphadenopathy. On a staging positron emission tomography computed tomography (PET-CT) scan, he was incidentally found to have an endotracheal tumour involving the anterolateral aspect of the mid-trachea. The tumour appeared to be well-vascularised at bronchoscopy and was confirmed as well-differentiated plasmablastic lymphoma. Plasmablastic lymphoma is a rare form of non-Hodgkin lymphoma and is associated with HIV. Tracheal involvement to the extent seen in our patient is exceptionally rare, and, to the best of our knowledge, has never been described.
Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring
Authors: Andrade Jason G. , Champagne Jean , Dubuc Marc , Deyell Marc W. , Verma Atul , Macle Laurent , Leong-Sit Peter , Novak Paul , Badra-Verdu Mariano , Sapp John , Mangat Iqwal , Khoo Clarence , Steinberg Christian , Bennett Matthew T. , Tang Anthony S.L. , Khairy Paul ,   For the CIRCA-DOSE Study Investigators, Parkash Ratika , Guerra Peter , Dyrda Katia , Rivard Lena , Racine Normand , Sterns Lawrence , Leather Rick , Seifer Colette , Jolly Umjeet , Raymond Jean-Marc , Roux Jean-Francois , Nault Isabelle , Sarrazin Jean-Francois , Ramanathan Krishnan , Cheung Christopher , Fordyce Christopher , McKinney Jimmy , Luong Christina , Rizkallah Jacques , Angaran Paul , Ha Andrew , Glover Benedict , Skanes Allan , Gula Lorne
Published: October 2019

Background:

Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence after atrial fibrillation (AF) ablation.

Methods:

We randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force–guided radiofrequency ablation (CF-RF; n=115), 4-minute cryoballoon ablation (Cryo-4; n=115), or 2-minute cryoballoon ablation (Cryo-2; n=116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 after ablation or a repeat ablation procedure at any time. Secondary end points included freedom from symptomatic arrhythmia and AF burden. All patients received an implantable loop recorder.

Results:

One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring was 53.9%, 52.2%, and 51.7% with CF-RF, Cryo-4, and Cryo-2, respectively (
P
=0.87). One-year freedom from symptomatic atrial tachyarrhythmia defined by continuous rhythm monitoring was 79.1%, 78.2%, and 73.3% with CF-RF, Cryo-4, and Cryo-2, respectively (
P
=0.26). Compared with the monitoring period before ablation, AF burden was reduced by a median of 99.3% (interquartile range, 67.8%–100.0%) with CF-RF, 99.9% (interquartile range, 65.3%–100.0%) with Cryo-4, and 98.4% (interquartile range, 56.2%–100.0%) with Cryo-2 (
P
=0.36). Serious adverse events occurred in 3 patients (2.6%) in the CF-RF group, 6 patients (5.3%) in the Cryo-4 group, and 7 patients (6.0%) in the Cryo-2 group, with no significant difference between groups (
P
=0.24). The CF-RF group had a significantly longer procedure duration but significantly shorter fluoroscopy exposure (
P
<0.001 vs cryoballoon groups).

Conclusions:

In this multicenter, randomized, single-blinded trial, CF-RF and 2 different regimens of cryoballoon ablation resulted in no difference in 1-year efficacy, which was 53% by time to first recurrence but >98% burden reduction as assessed by continuous cardiac rhythm monitoring.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01913522.
Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure
Authors: Li Yan , Thijs Lutgarde , Zhang Zhen-Yu , Asayama Kei , Hansen Tine W. , Boggia José , Björklund-Bodegård Kristina , Yang Wen-Yi , Niiranen Teemu J. , Ntineri Angeliki , Wei Fang-Fei , Kikuya Masahiro , Ohkubo Takayoshi , Dolan Eamon , Hozawa Atsushi , Tsuji Ichiro , Stolarz-Skrzypek Katarzyna , Huang Qi-Fang , Melgarejo Jesus D. , Tikhonoff Valérie , Malyutina Sofia , Casiglia Edoardo , Nikitin Yuri , Lind Lars , Sandoya Edgardo , Aparicio Lucas , Barochiner Jessica , Gilis-Malinowska Natasza , Narkiewicz Krzysztof , Kawecka-Jaszcz Kalina , Maestre Gladys E. , Jula Antti M. , Johansson Jouni K. , Kuznetsova Tatiana , Filipovský Jan , Stergiou George , Wang Ji-Guang , Imai Yutaka , O'Brien Eoin , Staessen Jan A. ,   On behalf of the International Database on Ambulatory and Home Blood Pressure in Relation to Cardiovascular Outcome Investigators*
Published: October 2019

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (≤60, 61–70, 71–80, and >80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (
P
<0.001) from 4.4 (95% CI, 4.0–4.7) to 86.3 (76.1–96.5) for all-cause mortality and from 4.1 (3.9–4.6) to 59.8 (51.0–68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (
P
≤0.0033) from 1.42 (1.19–1.69) to 1.09 (1.05–1.12) and from 1.70 (1.51–1.92) to 1.12 (1.07–1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension.
A contribution to the taxonomy of the genus Rhaponticoides (Asteraceae, Cardueae)

Authors: NEGARESH KAZEM
Published: October 2019

A taxonomic synopsis of the genus Rhaponticoides is presented. Rhaponticoides kultiassovii, R. lasiopoda, R. phyllopoda, R. androssovii, R. gontscharovii, R. alaica, R. modesti, R. ruthenica var. bipinnatifida, R. sect. Vicentinae, R. sect. Africanae, R. sect. Turkestanicae and R. sect. Aralocaspicae are proposed as new combinations. Full description for R. sect. Vicentinae, R. sect. Africanae, R. sect. Turkestanicae and R. sect. Aralocaspicae and a key for all sections are presented for the first time here. My previous descriptions of R. sect. Iranicae and R. sect. Ruthenicae are revised. Two names, R. kultiassovii and R. lasiopoda, are typified. In addition, type details, full descriptions, morphological comparisons, distribution and habitat of transferred taxa are given. Finally, a new list of species of the genus Rhaponticoides with their heterotypic synonyms, geographical distributions and chromosome numbers is provided.
Glossanodon macrocephalus, a new argentine fish (Argentinidae) from the Arabian Sea
Authors: BINEESH KINATTUMKARA , NASHAD MUSALIYARAKAM , KUMAR K.V. ANEESH , ENDO HIROMITSU
Published: October 2019

A new species of argentinid fish, Glossanodon macrocephalus Bineesh & Endo, from the Arabian Sea, off the southwestern coast of India, is described on the basis of four specimens (129–164 mm SL). The new species clearly differs from its congeners in the following combination of characters: dorsal-fin rays 10–11; pectoral-fin rays 21–23; anal-fin rays 12–13; pelvic-fin rays 11–12; branchiostegal rays 5; gill rakers on first arch 30–36; vertebrae 47–48; a patch of small conical teeth on middle of lower jaws; predorsal 49–51% SL; prepectoral 36–39% SL; prepelvic 57–58% SL; distance from pelvic to anal-fin origin 26–28% SL; head length 35–39% SL; eye diameter 22–26% HL; snout length 28–30% HL; location of anus immediately anterior to anal-fin origin; broad longitudinal black stripe above lateral line; dark spot on the base to half of pectoral fin; and no teeth on tongue. The new species is a benthopelagic dweller on muddy bottoms in depths of around 300–600 m.
Black Carbon Increases Frequency of Extreme ENSO Events
Authors: Lou Sijia , Yang Yang , Wang Hailong , Lu Jian , Smith Steven J. , Liu Fukai , Rasch Philip J.
Published: October 2019

El Niño–Southern Oscillation (ENSO) is the leading mode of Earth’s climate variability at interannual time scales with profound ecological and societal impacts, and it is projected to intensify in many climate models as the climate warms under the forcing of increasing CO2 concentration. Since the preindustrial era, black carbon (BC) emissions have substantially increased in the Northern Hemisphere. But how BC aerosol forcing may influence the occurrence of the extreme ENSO events has rarely been investigated. In this study, using simulations of a global climate model, we show that increases in BC emissions from both the midlatitudes and Arctic weaken latitudinal temperature gradients and northward heat transport, decrease tropical energy divergence, and increase sea surface temperature over the tropical oceans, with a surprising consequential increase in the frequency of extreme ENSO events. A corollary of this study is that reducing BC emissions might serve to mitigate the possible increasing frequency of extreme ENSO events under greenhouse warming, if the modeling result can be translated into the climate in reality.
IMERG V06: Changes to the Morphing Algorithm
Authors: Tan Jackson , Huffman George J. , Bolvin David T. , Nelkin Eric J.
Published: October 2019

As the U.S. Science Team’s globally gridded precipitation product from the NASA–JAXA Global Precipitation Measurement (GPM) mission, the Integrated Multi-Satellite Retrievals for GPM (IMERG) estimates the surface precipitation rates at 0.1° every half hour using spaceborne sensors for various scientific and societal applications. One key component of IMERG is the morphing algorithm, which uses motion vectors to perform quasi-Lagrangian interpolation to fill in gaps in the passive microwave precipitation field using motion vectors. Up to IMERG V05, the motion vectors were derived from the large-scale motions of infrared observations of cloud tops. This study details the changes introduced in IMERG V06 to derive motion vectors from large-scale motions of selected atmospheric variables in numerical models, which allow IMERG estimates to be extended from the 60°N–60°S latitude band to the entire globe. Evaluation against both instantaneous passive microwave retrievals and ground measurements demonstrates the general improvement in the precipitation field of the new approach. Most of the model variables tested exhibited similar performance, but total precipitable water vapor was chosen as the source of the motion vectors for IMERG V06 due to its competitive performance and global completeness. Continuing assessments will provide further insights into possible refinements of this revised morphing scheme in future versions of IMERG.
Effects of Under-Resolved Convective Dynamics on the Evolution of a Squall Line
Authors: Varble Adam , Morrison Hugh , Zipser Edward
Published: October 2019

Simulations of a squall line observed on 20 May 2011 during the Midlatitude Continental Convective Clouds Experiment (MC3E) using 750- and 250-m horizontal grid spacing are performed. The higher-resolution simulation has less upshear-tilted deep convection and a more elevated rear inflow jet than the coarser-resolution simulation in better agreement with radar observations. A stronger cold pool eventually develops in the 250-m run; however, the more elevated rear inflow counteracts the cold pool circulation to produce more upright convective cores relative to the 750-m run. The differing structure in the 750-m run produces excessive midlevel front-to-rear detrainment, reinforcing excessive latent cooling and rear inflow descent at the rear of the stratiform region in a positive feedback. The contrasting mesoscale circulations are connected to early stage deep convective draft differences in the two simulations. Convective downdraft condensate mass, latent cooling, and downward motion all increase with downdraft area similarly in both simulations. However, the 750-m run has a relatively greater number of wide and fewer narrow downdrafts than the 250-m run averaged to the same 750-m grid, a consequence of downdrafts being under-resolved in the 750-m run. Under-resolved downdrafts in the 750-m run are associated with under-resolved updrafts and transport mid–upper-level zonal momentum downward to low levels too efficiently in the early stage deep convection. These results imply that under-resolved convective drafts in simulations may vertically transport air too efficiently and too far vertically, potentially biasing buoyancy and momentum distributions that impact mesoscale convective system evolution.
Educational assortative mating, gender equality, and income differentiation across Europe: A simulation study
Authors: Eeckhaut Mieke CW , Stanfors Maria A
Published: October 2019

Demographic explanations for the rise in household income inequality include increased educational assortative mating and changes in the division of paid labour within families. Building on this research, the current study focuses on the connected nature of these two inequality-producing mechanisms, while at the same time bridging the divide with the economic literature on the role of income differentiation. Drawing on the 2004–2008 European Union Statistics on Income and Living Conditions, we consider variation across Europe in the disequalising effect of educational assortative mating and relate these patterns to the general characteristics of welfare state regimes, focusing on the degree of gender equality and income differentiation. First, we document large educational differentials in men’s and women’s income in Eastern Europe, and smaller differentials in Anglo-Saxon, Continental and, especially, Northern Europe. Next, we find that this variation in gender equality and income differentiation parallels variation in the potential contribution of educational assortative mating to educational differentiation in household income. While all countries display larger educational differentials in household income under the scenario of 100% educational homogamy, the biggest differences are found in Eastern Europe, and the smallest differences in the Nordic countries. These results suggest that educational assortative mating is less disequalising in countries with more gender equality and support for equal opportunities.
Improving Tracheostomy Care in Resource-Limited Settings
Authors: Sandler Mykayla L. , Ayele Nohamin , Ncogoza Isaie , Blanchette Susan , Munhall Daphne S. , Marques Brittanie , Nuss Roger C.
Published: October 2019

Objectives:

Tracheostomy care in leading pediatric hospitals is both multidisciplinary and comprehensive, including generalized care protocols and thorough family training programs. This level of care is more difficult in resource-limited settings lacking developed healthcare infrastructure and tracheostomy education among nursing and resident staff. The objective of this study was to improve pediatric tracheostomy care in resource-limited settings.

Methods:

In collaboration with a team of otolaryngologists, respiratory therapists, tracheostomy nurses, medical illustrators, and global health educators, image-based tracheostomy education materials and low-cost tracheostomy care kits were developed for use in resource-limited settings. In addition, a pilot study was conducted, implementing the image-based tracheostomy pamphlet, manual suctioning device and low-cost ambulatory supply kit (“Go-Bags”), within a low-fidelity simulated training course for nurses and residents in Kigali, Rwanda.

Results:

An image-based language and literacy-independent tracheostomy care manual was created and published on OPENPediatrics, an open-access online database of clinician-reviewed learning content. Participants of the training program pilot study reported the course to be of high educational and practical value, and described improved confidence in their ability to perform tracheostomy care procedures.

Conclusions:

Outpatient tracheostomy care may be improved upon by implementing image-based tracheostomy care manuals, locally-sourced tracheostomy care kits, and tailored educational material into a low-fidelity simulated tracheostomy care course. These materials were effective in improving technical skills and confidence among nurses and residents. These tools are expected to improve knowledge and skills with outpatient tracheostomy care, and ultimately, to reduce tracheostomy-related complications.
Preoperative Maxillary Sinus Imaging and the Outcome of Sinus Floor Augmentation and Dental Implants in Asymptomatic Patients
Authors: Ritter Amit , Rozendorn Noa , Avishai Gal , Rosenfeld Eli , Koren Ilan , Soudry Ethan
Published: October 2019

Objectives:

Preoperative maxillary sinus imaging findings have been suggested to be associated with complications and outcomes of sinus lift and dental implant procedures; nonetheless the evidence is controversial. The aim of this study was to examine the association between preoperative maxillary sinus imaging findings and outcomes of sinus lift and dental implant procedures in asymptomatic patients.

Methods:

We included all patients who underwent maxillary sinus lift and dental implant procedures between 2014 and 2017. Maxillary sinus imaging findings were extracted from pre-procedural dental computed tomography scans, and outcomes of the procedures were assessed.

Results:

A total of 145 procedures were included. No sinonasal symptoms were reported preoperatively. In 46% of cases maxillary sinus imaging was abnormal. The most common imaging finding was peripheral mucosal thickening (38%). Sinus floor cyst/polyp was identified in 13% of the cases, of which 47% occupied more than 50% of the sinus volume. Partial or complete opacification of the maxillary sinus was documented in 3% of cases. The sinus ostium and ostiomeatal complex were obstructed in 7% and 1%, respectively. Mucosal perforation was documented in 22% of cases and was inversely related to mucosal thickening ( P = 0.011). Other minor post-operative complications did not correlate with radiological findings. Post-surgical sinusitis was not observed in any of the patients regardless of pre-surgical imaging findings.

Conclusions:

Incidental maxillary sinus imaging findings such as mucosal swelling, cysts or polyps, regardless of their severity or size, and maxillary ostial obstruction may not need to be addressed prior to sinus augmentation and dental implant procedures in asymptomatic patients. Patients with complete sinus opacification should be referred to an otolaryngologist prior to surgery. Further controlled trials, in larger cohorts, are needed to corroborate our findings.