bluuebunny/crossref_metadata_2025_split huggingface dataset:
Debates—Hypothesis testing in hydrology: Theory and practice
Authors: Pfister Laurent , Kirchner James W. 
Published: February 2017

AbstractThe basic structure of the scientific method—at least in its idealized form—is widely championed as a recipe for scientific progress, but the day‐to‐day practice may be different. Here, we explore the spectrum of current practice in hypothesis formulation and testing in hydrology, based on a random sample of recent research papers. This analysis suggests that in hydrology, as in other fields, hypothesis formulation and testing rarely correspond to the idealized model of the scientific method. Practices such as “p‐hacking” or “HARKing” (Hypothesizing After the Results are Known) are major obstacles to more rigorous hypothesis testing in hydrology, along with the well‐known problem of confirmation bias—the tendency to value and trust confirmations more than refutations—among both researchers and reviewers. Nonetheless, as several examples illustrate, hypothesis tests have played an essential role in spurring major advances in hydrological theory. Hypothesis testing is not the only recipe for scientific progress, however. Exploratory research, driven by innovations in measurement and observation, has also underlain many key advances. Further improvements in observation and measurement will be vital to both exploratory research and hypothesis testing, and thus to advancing the science of hydrology.
Role of internal atmospheric variability in the 2015 extreme winter climate over the North American continent
Authors: Xie Jinbo , Zhang Minghua 
Published: February 2017

AbstractThe North American continent experienced an extremely anomalous dipole climate in the 2014/2015 winter with record‐breaking cold temperature anomalies in the east and warm anomalies in the west. The seasonable predictability of this extreme climate has not been understood. By using a large ensemble of model simulations with the Community Atmospheric Model (CAM4) and cluster analysis under observed sea surface temperature (SST) and sea ice conditions, we show that one of the simulation clusters can reproduce the observed dipole climate in this winter, but it is with low probability. This is in contrast to the two winters of 2013/2014 and 2015/2016 in which the leading clusters in surface temperature anomalies and the ensemble means are similar to observations in response to SST and sea ice conditions. Since the differences among the simulated clusters are entirely due to atmospheric initial conditions, we conclude that the 2014/2015 winter extreme dipole climate is a low‐probability event that is primarily caused by internal atmospheric variability based on the single‐model CAM4.
Lung and Pleural Tumours
Authors: Wittekind Christian , Asamura Hisao , Sobin Leslie H. 
Published: February 2017

Abstract
This chapter discusses lung and pleural tumours. The classifications apply to carcinomas of the lung including non&;#x02010;small cell and small cell carcinomas, bronchopulmonary carcinoid tumours and malignant mesothelioma of pleura. The regional lymph nodes extend from the supraclavicular region to the diaphragm. Direct extension of the primary tumour into lymph nodes is classified as lymph node metastasis. For each category, the rules of classification, anatomical subsites, and the regional lymph nodes are provided.
Skin Tumours
Authors: Wittekind Christian , Asamura Hisao , Sobin Leslie H. 
Published: February 2017

Abstract
In this chapter the following anatomical sites are identified by ICD&;#x02010;O topography rubrics: lip, eyelid, external ear, unspecified parts of face, scalp and neck, trunk, upper limb and shoulder, lower limb and hip, and scrotum. The chapter discusses the rules for classification, regional lymph nodes, and TNM clinical classification for the skin tumours. N &;#x02013; regional lymph nodes, M &;#x02013; distant metastasis, and pTNM pathological classification are also discussed.
Urological Tumours
Authors: Wittekind Christian , Asamura Hisao , Sobin Leslie H. 
Published: February 2017

Summary
This chapter discusses urological tumours. It focuses on tumours at the following sites: penis, prostate, testis, kidney, renal pelvis, ureter, urinary bladder, urethra and adrenal cortex. For each site, the rules for classification, anatomical subsites and regional lymph nodes are given. In addition, TNM clinical classification is also given for the sites.
Gynaecological Tumours
Authors: Brierley James D. , Gospodarowicz Mary K. , Wittekind Christian 
Published: February 2017

Abstract
Paediatric gynaecological and urological tumours and nodes and metastases thereof have been classified. Tumours have been classified into Tier 1 and Tier 2. Staging of gynaecological tumours corresponds to the FIGO staging.
Assessment of Treatment Outcome
Authors: Manola Judith , Xu Wei , Giantonio Bruce J. 
Published: February 2017

Summary
Cancer studies frequently employ clinical endpoints for outcome reporting in order to estimate treatment effect sizes. Most often these outcome assessments use time‐to‐event measures in addition to tumour response, toxicity and quality of life (QOL). The Kaplan‐Meier method is often used to estimate the actuarial rate for time‐to‐event measures. Non‐stratified or stratified log‐rank tests are frequently applied assessing the treatment effect among groups. The Cox proportional hazards regression model is commonly used to estimate the hazard ratio between different treatments. Because cancer outcome is often confounded by multiple other outcomes (e.g. various causes of death), competing risks regression models are used to assess the treatment effect. In addition, intermediary endpoints, such as changes in tumour size, tumour‐related chemical markers and tumour metabolism may also assist in evaluating new treatments. Therefore, the ability to accurately and reliably assess the direct antitumour effect of investigational therapies is critical for the optimal conduct of clinical trials. The goal of this chapter is to summarize general principles of cancer outcome reporting and estimation of treatment effect, and response assessment.
Lung
Authors: Ramalingam Suresh S. , Fernandez Felix , Higgins Kristin A. , Auffermann William F. , Khuri Fadlo R. 
Published: February 2017

Summary
Lung cancer is the leading cause of cancer‐related deaths worldwide. Non‐small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancer and includes adenocarcinoma, squamous cell carcinoma and large cell carcinoma histology. Treatment of NSCLC is based on stage at the time of diagnosis, histological subtype, molecular status and performance status of the patient. Treatments for early‐stage NSCLC are driven by curative intent, whereas for advanced or metastatic disease, palliation is the goal. Small cell lung cancer (SCLC) is treated with chemotherapy with or without radiation based on the stage. Modest improvements in survival have been noted for all stages of NSCLC in recent years, although outcomes for SCLC continue to be dismal. Recent advances in lung cancer include early detection by CT screening, incorporation of adjuvant chemotherapy and individualized therapy based on molecular status.
Kidney
Authors: Ferguson J. E. , Rathmell W. Kimryn , Wallen Eric M. 
Published: February 2017

Summary
Renal cell carcinoma is the third most common urological malignancy (behind prostate and bladder). Its clinical course is highly variable and difficult to predict. Generally, however, tumours confined to the kidney are highly curable through surgical removal, while metastatic tumours have a high mortality rate due in part to their resistance to traditional cytotoxic chemotherapy. However, recent identification of novel antiangiogenic and immunotherapeutic agents is dramatically improving the clinical course of metastatic disease. Furthermore, the increased utilization of cross‐sectional imaging in Western countries has resulted in earlier detection of small and curable cancers. Partial nephrectomy is increasingly utilized to remove these small tumours while preserving maximal kidney function. Current research aims to better understand which small renal masses require treatment and which can be observed, as well as to develop even more effective systemic therapies to prevent or treat metastatic disease.
Leukaemia
Authors: Zuckerman Tsila , Rowe Jacob M. 
Published: February 2017

Summary
Leukaemia, although not a common malignancy, poses a major challenge both in diagnosis and treatment. In recent years, a dramatic advance has been made in our understanding of the heterogeneous biology of this disease owing to innovative techniques such as whole‐genome sequencing. This has led to improved classification and genetic risk stratification and hence, to a refined risk‐adapted therapy. Novel drugs are under development with intention to be added as a targeted therapy alongside, or instead of, conventional chemotherapy. This chapter aims to review the current approach to diagnosis, treatment and prognosis of different leukaemias with an emphasis on new advances in the field.
Cervix
Authors: Denny Lynette , Van Wijk Leon 
Published: February 2017

Summary
Cervical cancer, a preventable disease with a clearly defined natural history and caused by infection with high‐risk types of the human papillomavirus (HPV), remains the third commonest cancer affecting women globally. Over 85% of cases are diagnosed in developing countries where the case‐to‐fatality rate ranges between 75% and 80%. Secondary prevention of cervical cancer in low income countries has failed to control the disease that affects women at an average age of 45–55 years. Diagnostic and treatment facilities in developed countries, along with functional screening programmes have made cervical cancer a well‐controlled and relatively rare disease in countries with robust health systems. In poor countries, women present with late‐stage disease and in most cases the disease is inevitably fatal. The introduction of new screening technologies and HPV vaccination offer new hope for the control of this common, yet preventable, disease.
Larynx and Hypopharynx
Authors: Agarwal Jai Prakash , Gupta Tejpal , Krishnatry Rahul , Joshi Amit , Dandekar Mitali 
Published: February 2017

Summary
The larynx and hypopharynx are common sites of origin for squamous cell cancers of the head and neck. The aim of treatment is to maximize disease control and survival with preservation of organ function and acceptably low acute and late morbidity. With recent emphasis on quality of life, the use of mutilating and extirpative surgery has rapidly declined worldwide, paving the way for conservative surgical techniques like lasers, endolaryngeal options and non‐surgical options. Platinum‐based concurrent definitive chemoradiation is generally considered the standard of care in the non‐surgical management of locally‐advanced laryngeal and hypopharyngeal cancer. Induction taxane‐based chemotherapy followed by platinum‐based concurrent chemoradiotherapy may be considered a reasonable alternative, although still investigational and unproven as equivalent to definitive concurrent chemoradiotherapy. Altered fractionation radiotherapy remains an option to intensify treatment if systemic treatments cannot be tolerated or are not available. The role of targeted therapy (cetuximab) continues to evolve with maximum benefit for patients ineligible for platinum‐based chemotherapy. Surgery still remains an important option for patients with cartilage involvement at initial diagnosis, poor response to neoadjuvant chemotherapy or residual/recurrent disease following an organ‐preservation protocol. Despite significant understanding of biology and important advances in management, outcomes for advanced laryngeal and hypopharyngeal cancers remain suboptimal. There is a need to identify robust prognostic and predictive factors to guide decision‐making, specify appropriate endpoints for organ and function preservation, and validate them in appropriately designed clinical trials prior to adoption in the clinic. This chapter provides a comprehensive summary of aetiology, clinical presentation, diagnosis, treatment and follow‐up, with a glimpse of current controversies, future advancements and research directions.
Skin
Authors: Porceddu Sandro V. , Veness Michael J. , Soyer H. Peter 
Published: February 2017

SummarySkin cancer is the most common cancer observed worldwide. This chapter focuses on non‐melanoma skin cancer (NMSC), specifically basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Merkel cell carcinoma (MCC). BCC is more common than SCC, while MCC is rare. NMSC commonly occurs on sun‐exposed areas, such as the head and neck region, with solar radiation as the major causative agent. Surgery is often the predominant treatment modality, as it provides high cure rates and histopathological information. Some patients may require adjuvant radiotherapy (RT). Alternative treatments when surgery is contraindicated or not the preferred option include radiotherapy, cryotherapy, photodynamic therapy (PDT) or topical agents. The development of regional and/or distant metastases is associated with a poorer prognosis. Patients with high‐risk features, including immunosuppression, warrant referral to specialized clinicians and multidisciplinary clinics.
Melanoma
Authors: Margolin Kim , O'Sullivan Brian , Pollock Raphael 
Published: February 2017

Summary
Melanoma arises in the skin but can be lethal in the brain. Surgery cures &gt;90% of melanoma patients, probably because the visibility of the skin allows early diagnosis. Surgery for melanoma is the mainstay for diagnosis, for therapy of limited nodal and metastatic disease and even for brain metastasis if single or symptomatic. Advanced melanoma, defined as unresectable multisite metastatic disease or locally‐advanced disease not amenable to curative resection, is treated with immunotherapy or molecularly‐targeted small molecule chemotherapy. Immunotherapy may cure or provide durable and deep remissions for a portion of patients. Molecularly‐targeted therapy is for patients with specific mutations and generally after failure of immunotherapy, since these agents have a limited duration of activity. Efforts to discover the mechanisms of resistance to immunotherapy and molecularly‐targeted therapy will inform new treatments and strategies likely to cure a larger proportion of melanoma patients.
Quantitative muscle ultrasound detects disease progression in Duchenne muscular dystrophy
Authors: Zaidman Craig M. , Wu Jim S. , Kapur Kush , Pasternak Amy , Madabusi Lavanya , Yim Sung , Pacheck Adam , Szelag Heather , Harrington Tim , Darras Basil T. , Rutkove Seward B. 
Published: February 2017

ObjectiveWe assessed changes in quantitative muscle ultrasound data in boys with Duchenne muscular dystrophy (DMD) and healthy controls to determine whether ultrasound can serve as a biomarker of disease progression. Two approaches were used: gray scale level (GSL), measured from the ultrasound image, and quantitative backscatter analysis (QBA), measured directly from the received echoes.MethodsGSL and QBA were obtained from 6 unilateral arm/leg muscles in 36 boys with DMD and 28 healthy boys (age = 2–14 years) for up to 2 years. We used a linear mixed effects model with random intercept and slope terms to compare trajectories of GSL, QBA, and functional assessments. We analyzed separately a subset of boys who initiated corticosteroids.ResultsCompared to healthy boys, increasing GSL in DMD boys >7.0 years old was first identified at 6 months (eg, anterior forearm slope difference of 1.16 arbitrary units/mo, p = 0.004, 95% confidence interval [CI] = 0.38–1.94); in boys ≤ 7 years old, differences in GSL first appeared at 12 months (0.82 arbitrary units/mo, p = 0.04, 95% CI = 0.075–1.565, in rectus femoris). QBA performed similarly to GSL (eg, DMD boys > 7 years old: 0.41dB/mo, p = 0.01, 95% CI = 0.096–0.72, in anterior forearm at 6 months). Ultrasound identified differences earlier than functional measures including 6‐minute walk and supine‐to‐stand tests. However, neither QBA nor GSL showed an effect of corticosteroid initiation.InterpretationQBA performs similarly to GSL, and both appear more sensitive than functional assessments for detecting muscle deterioration in DMD. Additional studies will be required to determine whether quantitative muscle ultrasound can detect therapeutic efficacy. Ann Neurol 2017;81:633–640
Complex mechanical conditioning of cell‐seeded agarose constructs can influence chondrocyte biosynthetic activity
Authors: DiFederico Erica , Shelton Julia C. , Bader Daniel L. 
Published: February 2017

ABSTRACTArticular cartilage with its inherently poor capacity for self‐regeneration represents a primary target for tissue engineering strategies, with approaches focusing on the in vitro generation of neo‐cartilage using chondrocyte‐seeded 3D scaffolds subjected to mechanical conditioning. Although uniaxial compression regimens have significantly up‐regulated proteoglycan synthesis, their effects on the synthesis of collagen have been modest. Articular cartilage is subjected to shear forces during joint motion. Accordingly, this study utilized an apparatus to apply biaxial loading to chondrocytes seeded within agarose constructs with endplates. The chondrocytes yielded a monotonic increase in proteoglycan synthesis both in free swelling culture up to day 8 and when the constructs were subjected to dynamic compression alone (15% amplitude at a frequency of 1 Hz for 48 h). However, when dynamic shear (10% amplitude at 1 Hz) was superimposed on dynamic compression, total collagen synthesis was also up‐regulated, within 3 days of culture, without compromising proteoglycan synthesis. Histological analysis revealed marked collagen deposition around individual chondrocytes. A significant proportion (50%) of collagen was released into the culture medium, suggesting that it had only been partially synthesized in its mature state. The overall biosynthetic activity was enhanced more when the biaxial stimulation was applied in a continuous mode as opposed to intermittent loading. Results of the present study strongly suggest that proteoglycan and collagen synthesis may be triggered by uncoupled mechanosensitive cellular responses. The proposed in vitro model and the prescribed conditioning protocols demonstrated that a short pre‐culture period is preferable to long free swelling culture condition as it enables a significantly higher up‐regulation of collagen. Biotechnol. Bioeng. 2017;114: 1614–1625. © 2017 Wiley Periodicals, Inc.
Liver transection using indocyanine green fluorescence imaging and hepatic vein clamping
Authors: Kawaguchi Y , Nomura Y , Nagai M , Koike D , Sakuraoka Y , Ishida T , Ishizawa T , Kokudo N , Tanaka N 
Published: February 2017

Abstract

Background
Three-dimensional (3D) imaging has facilitated liver resection with excision of hepatic veins by estimating the liver volume of portal and hepatic venous territories. However, 3D imaging cannot be used for real-time navigation to determine the liver transection line. This study assessed the value of indocyanine green (ICG) fluorescence imaging with hepatic vein clamping for navigation during liver transection.

Methods
Consecutive patients who underwent liver resection with excision of major hepatic veins between 2012 and 2013 were evaluated using ICG fluorescence imaging after clamping veins and injecting ICG. Regional fluorescence intensity (FI) values of non-veno-occlusive regions (FINon), veno-occlusive regions (FIVO) and ischaemic regions (FIIS) were calculated using luminance analysing software.

Results
Of the 21 patients, ten, four and seven underwent limited resection, monosegmentectomy/sectionectomy and hemihepatectomy respectively, with excision of major hepatic veins. Median veno-occlusive liver volume was 80 (range 30–458) ml. Fluorescence imaging visualized veno-occlusive regions as territories with lower FI compared with non-veno-occlusive regions, and ischaemic regions as territories with no fluorescence after intravenous ICG injection. Median FIIS/FINon was lower than median FIVO/FINon (0·22 versus 0·59; P = 0·002). There were no deaths in hospital or within 30 days, and only one major complication.

Conclusion
ICG fluorescence imaging with hepatic vein clamping visualized non-veno-occlusive, veno-occlusive and ischaemic regions. This technique may guide liver transection by intraoperative navigation, enhancing the safety and accuracy of liver resection.
Tetrahydroisoquinolines: New Inhibitors of Neutrophil Extracellular Trap (NET) Formation
Authors: Martinez Nancy E. , Zimmermann Tobias J. , Goosmann Christian , Alexander Tobias , Hedberg Christian , Ziegler Slava , Zychlinsky Arturo , Waldmann Herbert 
Published: February 2017

AbstractNeutrophils are short‐lived leukocytes that migrate to sites of infection as part of the acute immune response, where they phagocytose, degranulate, and form neutrophil extracellular traps (NETs). During NET formation, the nuclear lobules of neutrophils disappear and the chromatin expands and, accessorized with neutrophilic granule proteins, is expelled. NETs can be pathogenic in, for example, sepsis, cancer, and autoimmune and cardiovascular diseases. Therefore, the identification of inhibitors of NET formation is of great interest. Screening of a focused library of natural‐product‐inspired compounds by using a previously validated phenotypic NET assay identified a group of tetrahydroisoquinolines as new NET formation inhibitors. This compound class opens up new avenues for the study of cellular death through NET formation (NETosis) at different stages, and might inspire new medicinal chemistry programs aimed at NET‐dependent diseases.
Oxygen‐Assisted Hydrogenation of Jatropha‐Oil‐Derived Biodiesel Fuel over an Alumina‐Supported Palladium Catalyst To Produce Hydrotreated Fatty Acid Methyl Esters for High‐Blend Fuels
Authors: Mochizuki Takehisa , Abe Yohko , Chen Shih‐Yuan , Toba Makoto , Yoshimura Yuji 
Published: February 2017

AbstractThe partial hydrogenation of jatropha–oil–derived biodiesel fuel (BDF) with a high degree of unsaturated fatty acid tails was successfully performed on an alumina‐supported palladium catalyst, denoted Pd/γ‐Al2O3, under mild conditions (100 °C and 0.5 MPa) to produce hydrotreated fatty acid methyl esters (H‐FAMEs) enriched in monounsaturated components. Trace amounts of peroxides contained in the oil feedstock or the co‐feeding of proper amounts of molecular oxygen (400–1500 ppm) resulted in enhanced activity and durability of Pd/γ‐Al2O3. The produced H‐FAMEs exhibited significantly improved oxidation stability and uncompromised cold‐flow properties, and they can serve as an excellent source of high‐quality BDFs, particularly for high‐blend fuels.