bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of hospitalisation for severe complications of influenza virus infection in Japanese patients between 2012 and 2016: a cross-sectional study using routinely collected administrative data
Authors: Yokomichi Hiroshi , Mochizuki Mie , Lee Joseph Jonathan , Kojima Reiji , Yokoyama Tetsuji , Yamagata Zentaro 
Published: January 2019

ObjectiveTo calculate the incidence of hospitalisation due to acute respiratory failure, pneumonia, acute respiratory distress syndrome (ARDS), febrile seizures and encephalitis/encephalopathy among influenza-positive patients in Japan, where point-of-care tests are routinely used to diagnose influenza.DesignA cross-sectional study using routinely collected data.SettingJapanese clinics and hospitals between 2012 and 2016.ParticipantsJapanese patients aged 0–74 years diagnosed with influenza by a rapid test in employment-related health insurance records.Primary outcome measuresIncidence of hospitalisation per 100 000 influenza-positive episodes.ResultsWe included over 16 million influenza-positive episodes, 1.0% of whom were hospitalised. Of these, 3361 were acute respiratory failure, 27 253 pneumonia, 18 ARDS, 2603 febrile seizure and 159 encephalitis/encephalopathy. The percentage of hospitalisations by age was 2.96% of patients aged 0–1 years, 0.77% aged 2–5, 0.51% aged 6–12, 0.78% aged 13–18, 1.36% aged 19–44, 1.19% aged 45–64, and 2.21% aged 65–74. The incidence of hospitalisations from these five complications combined was highest in influenza-positive patients aged 0–1 years (943 per 100 000) compared with 307 in those aged 2–5 years and 271 in those aged 65–74 years. For pneumonia, the incidence was highest for influenza-positive patients aged 0–5 years and 65 years or more. There were statistically significant decreasing trends over the years in the incidence of all-cause hospitalisations, pneumonia and febrile seizures.ConclusionsJapanese administrative data revealed that 1.0% of influenza-positive patients aged under 75 years were hospitalised. Male patients had a higher incidence of pulmonary complications and febrile seizures. Children aged 0–5 years and adults aged 65–74 years were at high risk of being admitted to hospital for pneumonia.
Readability assessment of package leaflets of biosimilars
Authors: Piñero-López María Ángeles , Figueiredo-Escribá Carlos , Modamio Pilar , Lastra Cecilia F , Mariño Eduardo L 
Published: January 2019

ObjectivesTo assess the degree of readability and the length of the package leaflets of biosimilars.SettingThe package leaflets analysed were downloaded from the European Medicines Agency (EMA) website.ParticipantsThe study sample included the package leaflets written in English of all the biosimilars that were authorised by the EMA on 31 August 2017, and whose content was available via the internet on that date (n=35).DesignThis was a cross-sectional analytical study. The readability of the package leaflets of all biosimilars authorised by the EMA in August 2017 was determined applying the Flesch and Flesch-Kincaid formulas. The influence of the following variables on the readability and length was also analysed: package leaflet section, type of biosimilar, date of first authorisation of the biosimilar and type of medicine.ResultsA considerable variation of the package leaflets length was found (3154±803). The readability of all the package leaflets overtook the recommended value for health-related written materials taking into account Flesch-Kincaid Index, and none of the package leaflets were easy to understand according to the Flesch Index. Statistically significant differences (p<0.05) were observed between the sections of package leaflets in readability indices and length. The most difficult sections to understand were those related with the therapeutic indication of medicine and the possible side effects.ConclusionsPackage leaflets for authorised biosimilars may not fulfil the function for which they were designed. The competent organisations could be informed about the possible negative effect on the use of this type of medicines.
Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease
Authors: Wong Vincent Wai-Sun , Irles Marie , Wong Grace Lai-Hung , Shili Sarah , Chan Anthony Wing-Hung , Merrouche Wassil , Shu Sally She-Ting , Foucher Juliette , Le Bail Brigitte , Chan Wah Kheong , Chan Henry Lik-Yuen , de Ledinghen Victor 
Published: January 2019

ObjectiveThe latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients’ body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis.DesignWe prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy.Results391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75–0.88 for F2–4, 0.83–0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe.ConclusionHigh BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.
Long-term testosterone deficiency modifies myofilament and calcium-handling proteins and promotes diastolic dysfunction in the aging mouse heart
Authors: Ayaz Omar , Banga Shubham , Heinze-Milne Stefan , Rose Robert A. , Pyle W. Glen , Howlett Susan E. 
Published: January 2019

The impact of long-term gonadectomy (GDX) on cardiac contractile function was explored in the setting of aging. Male mice were subjected to bilateral GDX or sham operation (4 wk) and investigated at 16–18 mo of age. Ventricular myocytes were field stimulated (2 Hz, 37°C). Peak Ca2+transients (fura 2) and contractions were similar in GDX and sham-operated mice, although Ca2+transients (50% decay time: 45.2 ± 2.3 vs. 55.6 ± 3.1 ms, P < 0.05) and contractions (time constant of relaxation: 39.1 ± 3.2 vs. 69.5 ± 9.3 ms, P < 0.05) were prolonged in GDX mice. Action potential duration was increased in myocytes from GDX mice, but this did not account for prolonged responses, as Ca2+transient decay was slow even when cells from GDX mice were voltage clamped with simulated “sham” action potentials. Western blots of proteins involved in Ca2+sequestration and efflux showed that Na+/Ca2+exchanger and sarco(endo)plasmic reticulum Ca2+-ATPase type 2 protein levels were unaffected, whereas phospholamban was dramatically higher in ventricles from aging GDX mice (0.24 ± 0.02 vs. 0.86 ± 0.13, P < 0.05). Myofilament Ca2+sensitivity at physiological Ca2+was similar, but phosphorylation of essential myosin light chain 1 was reduced by ≈50% in ventricles from aging GDX mice. M-mode echocardiography showed no change in systolic function (e.g., ejection fraction). Critically, pulse-wave Doppler echocardiography showed that GDX slowed isovolumic relaxation time (12.9 ± 0.9 vs. 16.9 ± 1.0 ms, P < 0.05), indicative of diastolic dysfunction. Thus, dysregulation of intracellular Ca2+and myofilament dysfunction contribute to deficits in contraction in hearts from testosterone-deficient aging mice. This suggests that low testosterone helps promote diastolic dysfunction in the aging heart.NEW & NOTEWORTHY The influence of long-term gonadectomy on contractile function was examined in aging male hearts. Gonadectomy slowed the decay of Ca2+transients and contractions in ventricular myocytes and slowed isovolumic relaxation time, demonstrating diastolic dysfunction. Underlying mechanisms included Ca2+dysregulation, elevated phospholamban protein levels, and hypophosphorylation of a myofilament protein, essential myosin light chain. Testosterone deficiency led to intracellular Ca2+dysregulation and myofilament dysfunction, which may facilitate diastolic dysfunction in the setting of aging.
Mouse PVRIG Has CD8+ T Cell–Specific Coinhibitory Functions and Dampens Antitumor Immunity
Authors: Murter Benjamin , Pan Xiaoyu , Ophir Eran , Alteber Zoya , Azulay Meir , Sen Rupashree , Levy Ofer , Dassa Liat , Vaknin Ilan , Fridman-Kfir Tal , Salomon Ran , Ravet Achinoam , Tam Ada , Levin Doron , Vaknin Yakir , Tatirovsky Evgeny , Machlenkin Arthur , Pardoll Drew , Ganguly Sudipto 
Published: January 2019

AbstractA limitation to antitumor immunity is the dysfunction of T cells in the tumor microenvironment, in part due to upregulation of coinhibitory receptors such as PD-1. Here, we describe that poliovirus receptor–related immunoglobulin domain protein (PVRIG) acts as a coinhibitory receptor in mice. Murine PVRIG interacted weakly with poliovirus receptor (PVR) but bound poliovirus receptor–like 2 (PVRL2) strongly, making the latter its principal ligand. As in humans, murine NK and NKT cells constitutively expressed PVRIG. However, when compared with humans, less PVRIG transcript and surface protein was detected in murine CD8+ T cells ex vivo. However, activated CD8+ T cells upregulated PVRIG expression. In the mouse tumor microenvironment, infiltrating CD8+ T cells expressed PVRIG whereas its ligand, PVRL2, was detected predominantly on myeloid cells and tumor cells, mirroring the expression pattern in human tumors. PVRIG-deficient mouse CD8+ T cells mounted a stronger antigen-specific effector response compared with wild-type CD8+ T cells during acute Listeria monocytogenes infection. Furthermore, enhanced CD8+ T-cell effector function inhibited tumor growth in PVRIG−/− mice compared with wild-type mice and PD-L1 blockade conferred a synergistic antitumor response in PVRIG−/− mice. Therapeutic intervention with antagonistic anti-PVRIG in combination with anti–PD-L1 reduced tumor growth. Taken together, our results suggest PVRIG is an inducible checkpoint receptor and that targeting PVRIG–PVRL2 interactions results in increased CD8+ T-cell function and reduced tumor growth.See related article on p. 257
A 1D-Var Approach to Retrieve Clear-Sky Wet Tropospheric Correction from Current and Future Altimetry Missions
Authors: Hermozo Laura , Eymard Laurence , Karbou Fatima , Picard Bruno , Pardé Mickael 
Published: January 2019

AbstractStatistical methods are usually used to provide estimations of the wet tropospheric correction (WTC), necessary to correct altimetry measurements for atmospheric path delays, using brightness temperatures measured at two or three low frequencies from a passive microwave radiometer on board the altimeter mission. Despite their overall accuracy over oceanic surfaces, uncertainties still remain in specific regions of complex atmospheric stratification. Thus, there is still a need to improve the methods currently used by taking into account the frequency-dependent information content of the observations and the atmospheric and surface variations in the surroundings of the observations. In this article we focus on the assimilation of relevant passive microwave observations to retrieve the WTC over ocean using different altimeter mission contexts (current and future, providing brightness temperature measurements at higher frequencies in addition to classical low frequencies). Data assimilation is performed using a one-dimensional variational data assimilation (1D-Var) method. The behavior of the 1D-Var is evaluated by verifying its physical consistency when using pseudo- and real observations. Several observing-system simulation experiments are run and their results are analyzed to evaluate global and regional WTC retrievals. Comparisons of 1D-Var-based TWC retrieval and reference products from classical WTC retrieval algorithms or radio-occultation data are also performed to assess the 1D-Var performances.
Prognostic significance of PCT and CRP evaluation for adult ICU patients with sepsis and septic shock: retrospective analysis of 59 cases
Authors: Cui Na , Zhang Hongwei , Chen Zhi , Yu Zhanbiao 
Published: January 2019

Objective To investigate the prognostic significance of serum procalcitonin (PCT) and C-reactive protein (CRP) in patients with sepsis and those with septic shock. Methods Fifty-nine patients were divided into sepsis and septic shock groups, as well as survivor and non-survivor groups, according to the severity of the disease and patient survival. Serum PCT and CRP measurements at the time of hospitalization in the intensive care unit were examined. Results On the 2nd, 3rd, and 5th days, the CRP level was higher in the non-survivor group than in the survivor group, and the serum CRP level was higher in patients in the septic shock group than in patients in the sepsis group. Regarding changes in serum PCT level in each group, the levels of PCT were significantly different between non-survivor and survivor groups, whereas they did not differ between patients in the sepsis and septic shock groups. Serum PCT kinetics (ΔPCT) were similar between groups. Conclusions Serum PCT and CRP have good clinical diagnostic and prognostic value for patients with sepsis and septic shock. Kinetic studies of PCT and CRP can improve sensitivity and accuracy when evaluating the prognosis of patients with sepsis and those with septic shock.
Ointment Pseudo-Cheilitis: A Disease Distinct From Factitial Cheilitis. A Series of 13 Patients From São Paulo, Brazil
Authors: Nico Marcello Menta Simonsen , Dwan Alexandre Jack , Lourenço Silvia Vanessa 
Published: January 2019

Background: The terms exfoliative cheilitis, factitial cheilitis, and morsicatio labiorum are used to describe self-inflicted lesions of the lip. Objective: Here we report and analyze clinical, pathological, and therapeutic data on 13 patients with a form of factitial cheilitis that we believe should be considered a separate entity. Results: Eight patients were male and 5 patients were female. All patients reported pain and presented with crusts consisting of dried saliva and topical medications adherent to the surface of the lips. These patients expressed great concern with their condition, and reported several previous, ineffective treatments. Simple reassurance only was not effective; saline compresses alleviated symptoms for a few patients. Most patients were lost to follow-up. Biopsies were not performed on all patients. Conclusion: This particular type of cheilitis artefacta has been previously described, but some features described herein are new and allow a specific approach: patient’s behavior, the “protrusion sign,” and possible improvement with antidepressants. For these cases, we propose the term ointment pseudo-cheilitis because it comprises the nature of the attached material and the lack of true inflammation. Further psychiatric characterization is a logical next step in further characterizing this difficult-to-treat condition.
Effect And Predictive Value Of Routine Preoperative Laboratory Testing For Endoscopic Retrograde Cholangiopancreatography
Authors: Jokelainen J. , Ismail S. , Kylänpää L. , Udd M. , Mustonen H. , Lindström O. , Pöyhiä R. 
Published: January 2019

Background and Aims: Several studies and guidelines are questioning routine preoperative laboratory tests in surgical and endoscopic procedures. Their effect in endoscopic retrograde cholangiopancreatography is not currently known. This study was carried out to evaluate the risk of adverse effects in endoscopic retrograde cholangiopancreatography and their association with preoperative lab tests. Materials and Methods: A single-center, prospective observational study on all 956 patients undergoing 1196 endoscopic retrograde cholangiopancreatographies in the Endoscopy Unit of Helsinki University Central Hospital from 1 March 2012 to 28 February 2013. Routine preoperative laboratory test results (basic blood count, creatinine, potassium, sodium, international normalized ratio/thromboplastin time, and amylase), health status, medication, and demographic information of all patients were analyzed in relation to adverse effects related to endoscopic retrograde cholangiopancreatography and procedural sedation. Results: Multivariate analysis showed post–endoscopic retrograde cholangiopancreatography pancreatitis (43 cases, 3.6%) to have no association with abnormal routine preoperative laboratory tests. Respiratory depression caused by sedation (128 cases, 11%) was not associated with abnormal routine preoperative laboratory tests, and anemia was found to be a slightly protecting factor. Cardiovascular depression caused by sedation was associated with thrombocytopenia (odds ratio = 1.87, p = 0.025) and, in male patients, hyponatremia (odds ratio = 3.66, p < 0.001). Incidence of other adverse effects was too low for statistical analysis. Conclusion: Routine universal preoperative lab testing was not found to be successful in predicting adverse effects in endoscopic retrograde cholangiopancreatography procedures. Laboratory testing should be done focusing on each patient’s individual needs.
Role of circular RNAs in cardiovascular diseases
Authors: Gong Xue , Wu Gengze , Zeng Chunyu 
Published: January 2019

Over the last several decades, cardiovascular diseases largely increase the morbidity and mortality especially in developed countries, affecting millions of people worldwide. Although extensive work over the last two decades attempted to decipher the molecular network of regulating the pathogenesis and progression of these diseases, evidences from clinical trials with newly revealed targets failed to show more evidently salutary effects, indicating the inefficiency of understanding the complete regulatory landscape. Recent studies have shifted their focus from coding genes to the non-coding ones, which consist of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and the lately re-discovered a unique group of RNAs—circular RNAs (circRNAs). As the focus now has been shifted to the newly identified group of non-coding RNAs, circRNAs exhibit stability, highly conservation and relative enriched expression abundance in some cases, which are distinct from their cognate linear counterparts—lncRNAs. So far, emerging evidence begins to support the critical role of circRNAs in organogenesis and pathogenesis as exemplified in the central nervous system, and could be just as implicative in the cardiovascular system, suggesting a therapeutic perspective in related diseases. Impact statement Circular RNAs are important regulators of multiple biological processes such as organogenesis and oncogenesis. Although the bulk of concerning studies focused on revealing their diversified roles in various types of cancers, reports began to accumulate in cardiovascular field these days. We summarize circular RNAs implicated in cardiovascular diseases, aiming to highlight the advances in the knowledge of such diseases and their potential of being promising target for diagnosis and therapy.
Percutaneous‐transhepatic‐endoscopic rendezvous procedures are effective and safe in patients with refractory bile duct obstruction
Authors: Bokemeyer Arne , Müller Friederike , Niesert Hannah , Brückner Markus , Bettenworth Dominik , Nowacki Tobias , Beyna Torsten , Ullerich Hansjörg , Lenze Frank 
Published: January 2019

BackgroundPercutaneous‐transhepatic‐endoscopic rendezvous procedures (PTE‐RVs) are rescue approaches used to facilitate biliary drainage.ObjectiveThe objective of this article is to evaluate the safety and the technical success of PTE‐RVs in comparison with those of percutaneous transhepatic cholangiographies (PTCs).MethodsPercutaneous procedures performed over a 10‐year period were retrospectively analyzed in a single‐center cohort. Examinations were performed because of a previous or expected failure of standard endoscopic methods including endoscopic retrograde cholangiography (ERC) or balloon‐assisted ERC to achieve biliary access.ResultsIn total, 553 percutaneous procedures including 163 PTE‐RVs and 390 PTCs were performed. Overall, 71.3% of the patients suffered from malignant disease with pancreas‐carcinoma (32.8%) and cholangio‐carcinoma (19.0%) as the most frequent, while 28.7% of the patients suffered from benign disease. Many patients had a postoperative change in bowel anatomy (50.8%).PTC had a higher technical success rate (89.7%); however, the technical success rate of PTE‐RVs was still high (80.4%; p < 0.003). Overall complications occurred in 23.5% of all procedures. Significantly fewer complications occurred after performing PTE‐RVs than after PTCs (16.6% vs 26.4%; p = 0.037).ConclusionBeside a high technical efficacy of PTE‐RVs, significantly fewer complications occur following PTE‐RVs than following PTCs; thus, PTE‐RV should be preferred over PTC alone in selected patients.
Intrahepatic fibrin(ogen) deposition drives liver regeneration after partial hepatectomy in mice and humans
Authors: Groeneveld Dafna , Pereyra David , Veldhuis Zwanida , Adelmeijer Jelle , Ottens Petra , Kopec Anna K. , Starlinger Patrick , Lisman Ton , Luyendyk James P. 
Published: January 2019

AbstractPlatelets play a pivotal role in stimulating liver regeneration after partial hepatectomy in rodents and humans. Liver regeneration in rodents is delayed when platelets are inhibited. However, the exact mechanisms whereby platelets accumulate and promote liver regeneration remain uncertain. Thrombin-dependent intrahepatic fibrin(ogen) deposition was recently reported after partial hepatectomy (PHx) in mice, but the role of fibrin(ogen) deposits in liver regeneration has not been investigated. We tested the hypothesis that fibrin(ogen) contributes to liver regeneration by promoting intrahepatic platelet accumulation and identified the trigger of rapid intrahepatic coagulation after PHx. PHx in wild-type mice triggered rapid intrahepatic coagulation, evidenced by intrahepatic fibrin(ogen) deposition. Intrahepatic fibrin(ogen) deposition was abolished in mice with liver-specific tissue factor deficiency, pinpointing the trigger of coagulation after PHx. Direct thrombin activation of platelets through protease-activated receptor-4 did not contribute to hepatocyte proliferation after PHx, indicating that thrombin contributes to liver regeneration primarily by driving intrahepatic fibrin(ogen) deposition. Fibrinogen depletion with ancrod reduced both intrahepatic platelet accumulation and hepatocyte proliferation after PHx, indicating that fibrin(ogen) contributes to liver regeneration after PHx by promoting intrahepatic platelet accumulation. Consistent with the protective function of fibrin(ogen) in mice, low postoperative plasma fibrinogen levels were associated with liver dysfunction and mortality in patients undergoing liver resection. Moreover, increased intrahepatic fibrin(ogen) deposition was evident in livers of patients after liver resection but was remarkably absent in patients displaying hepatic dysfunction postresection. The results suggest a novel mechanism whereby coagulation-dependent intrahepatic fibrin(ogen) deposition drives platelet accumulation and liver regeneration after PHx.