bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of nedaplatin and amrubicin as first‐line treatment for advanced squamous cell lung cancer
Authors: Taniguchi Hirokazu , Yamaguchi Hiroyuki , Dotsu Yosuke , Shimada Midori , Gyotoku Hiroshi , Senju Hiroaki , Takemoto Shinnosuke , Kitazaki Takeshi , Fukuda Masaaki , Ogawara Daiki , Soda Hiroshi , Nakatomi Katsumi , Sugasaki Nanae , Kinoshita Akitoshi , Nagashima Seiji , Ikeda Takaya , Nakamura Yoichi , Sakamoto Noriho , Obase Yasushi , Fukuda Minoru , Mukae Hiroshi 
Published: July 2019

BackgroundThe first‐line treatment for squamous cell lung cancer (SCC) has not necessarily been established; however, our previous exploratory study suggested that the combination of nedaplatin and amrubicin would be a promising treatment approach for patients with SCC. Therefore, a phase II study of this chemotherapeutic combination was designed to evaluate its efficacy and safety for treatment‐naïve patients with advanced SCC.MethodsA total of 21 treatment‐naïve patients with stage IIIB/IV or postoperative recurrent SCC were enrolled from six institutions. Nedaplatin (100 mg/m2) on day 1 and amrubicin (25 mg/m2) on days 1–3 were administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR), while the secondary endpoints included overall survival (OS), progression‐free survival (PFS), and drug toxicities.ResultsPartial response was observed in seven of 21 cases (ORR, 33.3%; 95% confidence interval [CI], 14.5–52.2). Disease control rate, which includes stable disease, was 71.4%. Median OS and PFS was 14.6 and 4.1 months, respectively. This regimen did not cause any treatment‐related deaths. Grade 3/4 neutropenia developed in 8 of 21 cases (38.1%); however, febrile neutropenia developed in only 9.5% of the cases. Grade 3/4 gastrointestinal or neuromuscular toxicities were not observed.ConclusionThe efficacy of the combination of nedaplatin and amrubicin was comparable to that of other conventional chemotherapeutic regimens for treatment‐naïve patients with advanced SCC, and no severe gastrointestinal or neuromuscular toxicities were observed. This combination therapy may be an alternative treatment approach, particularly in patients who cannot tolerate gastrointestinal or neuromuscular toxicities.
Supervised consumption sites: a nuanced assessment of the causal evidence
Authors: Caulkins Jonathan P. , Pardo Bryce , Kilmer Beau 
Published: July 2019

AbstractBackground and AimsSupervised consumption sites (SCS) operate in more than 10 countries. SCS have mostly emerged as a bottom‐up response to crises, first to HIV/AIDS and now overdose deaths, in ways that make rigorous evaluation difficult. Opinions vary about how much favorable evidence must accumulate before implementation. Our aim was to assess the nature and quality of evidence on the consequences of implementing SCS.MethodsWe reviewed the higher‐quality SCS literature, focusing on articles evaluating natural experiments and mathematical modeling studies that estimate costs and benefits. We discuss the evidence through the lens of three types of decision‐makers and from three intellectual perspectives.ResultsMillions of drug use episodes have been supervised at SCS with no reported overdose deaths; however, uncertainties remain concerning the magnitude of the population‐level effects. The published literature on SCS is large and almost unanimous in its support, but limited in nature and the number of sites evaluated. It can also overlook four key distinctions: (1) between outcomes that occur within the facility and possible spillover effects on behavior outside the SCS; (2) between effects of supervising consumption and the effects of other services offered, such as syringe or naloxone distribution; (3) between association and causation; and (4) between effectiveness and the cost‐effectiveness of SCS compared to other interventions.ConclusionsThe causal evidence for favorable outcomes of supervised consumption sites is minimal, but there appears to be little basis for concern about adverse effects. This raises the question of how context and priors can affect how high the bar is set when deciding whether to endorse supervised consumption sites. The literature also understates distinctions and nuances that need to be appreciated to gain a rich understanding of how a range of stakeholders should interpret and apply that evidence to a variety of decisions.
Oral manifestations of illicit drug use
Authors: Teoh L , Moses G , McCullough MJ 
Published: July 2019

AbstractThe use of illicit and misuse of licit drugs is a global public health problem, with illicit drug use being responsible for 1.8% of the total disease burden in Australia in 2011. Oral adverse effects associated with illicit drug use are well‐established, with aggressive caries, periodontitis, bruxism, poor oral hygiene and general neglect documented. Other factors such as a high cariogenic diet and lifestyle, social and psychological factors compound the poorer oral health in illicit drug users. Literature has shown that the oral health‐related quality of life among injecting drug users is poorer compared with the Australian general population and the overall quality of life of addicted people correlates with caries experience. Thus, the role of the dentist is imperative in managing the oral health of these individuals. Given their widespread recreational use, it is likely that dental practitioners will encounter patients who are regular or past users of illicit drugs. The aim of this article is to describe the prevalence and mechanism of action of commonly used illicit drugs in Australia, including cannabis, methamphetamine, cocaine and heroin and to inform dentists about the common orofacial presentations of their side effects to help with patient management.
Viable versus nonviable positive margins in Ewing sarcoma and associated recurrence rates: A systematic review
Authors: El Demellawy Dina , Menzies‐Toman Danielle , Murphy Michelle , Kabir Nooh , Shaw Ashley , Chernetsova Elizavita , Serlo Joni A. , de Nanassy Joseph 
Published: July 2019

AbstractResidual tumor after curative intent therapy in patients with Ewing's sarcoma is of great clinical significance. Surgeons use the resection margin to indicate the completeness of a surgical excision. However, this margin may be either nonviable/necrotic or viable. This systematic review examines the 5‐year event‐free survival rate and local recurrence as a function of positive resection margins that are nonviable/necrotic versus those that are viable. Multiple databases were searched using the Ovid interface. After full text screening, 45 articles that reported either margin or postchemotherapy histology and one or more outcomes of interest were identified, and two articles reported on margin and histology simultaneously. An attempt was made to contact the remaining authors and one author was able to provide additional data. The data from the three studies suggest that prognosis in ES depends on both margin involvement and the postchemotherapy histological response simultaneously. However, radiation therapy likely improves local control in patients with inadequate surgical margins, regardless of histological response. This is an area where there is a paucity of evidence that needs to be rectified to ensure that ES patients are provided the highest quality of evidence‐based care.
External‐beam radiation therapy versus surgery in the treatment of hepatocellular carcinoma with inferior vena cava/right atrium tumor thrombi
Authors: Li Yong , Liu Fenghua , Yang Liang , Meng Yan , Li Aijun , Pan Mianshun 
Published: July 2019

AbstractBackgroundBoth surgery and external‐beam radiotherapy are effective treatments for hepatocellular carcinoma (HCC) patients with inferior vena cava/right atrium (IVC/RA) tumor thrombi. At present, it is not clear which modality is more suitable. We therefore compared outcomes between surgery and radiotherapy for these patients.MethodsWe retrospectively reviewed 108 HCC patients with IVC/RA tumor thrombi who were referred for surgery (n = 51) and external‐beam radiotherapy (n = 57) at three institutions. Different surgical methods were selected according to the classification of the tumor thrombus. Radiotherapy was designed to focus on primary intrahepatic tumors and tumor thrombi. Predictors of time to progression (TTP) were identified by using univariate and multivariate analyses.ResultsThe median TTP was significantly longer in the radiotherapy group than in the surgery group (5.0 months vs 4.2 months; P = 0.010). The multivariate analysis revealed that independent factors predicting shorter TTP were treatment with surgery (HR = 0.577; 95% CI, 0.385–0.865; P = 0.008) and intrahepatic tumor size larger than 10 cm (HR = 0.561; 95% CI, 0.342–0.919; P = 0.022). The median survival times for the radiotherapy and surgery groups were 12.8 and 14.5 months, respectively; the two groups did not have a significant difference in survival (P = 0.466).ConclusionsFor HCC patients with IVC/RA tumor thrombi, treatment with external‐beam radiotherapy and intrahepatic tumor size smaller than 10 cm may predict longer TTP. Compared with complicated surgery, radiotherapy, as a noninvasive treatment modality, may be more likely to be accepted.
Trend analysis and regional tumor incidence in Germany for testicular cancer between 2003 and 2014
Authors: Brandt M. P. , Gust K. M. , Bon D. , Tsaur I. , Thomas C. , Neisius A. , Haferkamp A. , Herrmann E. , Bartsch G. 
Published: July 2019

AbstractBackgroundTesticular germ cell tumor (TGCT) is one the most common solid tumors in men between the age of 15 and 35 with an overall incidence rate of 1–1.5 %. Epidemiologic studies have demonstrated different incidence patterns in western civilized countries with overall rising incidence trends.ObjectiveTo analyze differences in regional tumor incidence rates for TGCT and perform a trend analysis for TGCT between 2003 and 2014 in Germany.Material and methodsTGCT cases in Germany which were diagnosed between 2003 and 2014 were provided by the Robert‐Koch‐Institute, Berlin. For statistical analysis, cluster and spatial scan tests according to Kulldorff were used for cases with seminoma and non‐seminoma. Results are presented in administrative districts and graphically illustrated. We performed a trend‐analysis in order to evaluate age‐adjusted incidence trends in Germany. Tests were two‐sided with a level of significance of α=0.05.ResultsIn total we included 35,066 patients. Overall, 22,634 cases had newly diagnosed seminoma and 12,432 were diagnosed as non‐seminoma. Maximum incidence of seminoma and non‐seminoma was observed for age‐group 38–40 years and 26–28 years, respectively. No second peak for the incidences of seminoma and non‐seminoma with respect to age were observed. Cluster analysis revealed areas with high and low incidence rates as well as slightly different spatial distribution in Germany between seminoma and nonseminoma. Furthermore, there was no significant increase in age‐adjusted incidence rates over the reviewed time period in both cohorts.DiscussionIn this study differences in reginal tumor incidence rates for seminoma and non‐seminoma are reported with both tumor entities revealing distinct clusters. Furthermore, tumor incidence trends for seminoma and nonseminoma between 2003 and 2014 were stable which might indicate the beginning of a plateau phase for TGCT incidence rates in Germany.ConclusionIn this analysis we were able to identify regions with significantly higher tumor incidence rates for both seminoma and non‐seminoma which were specific for these two subtypes. Furthermore, trend analysis revealed a steady incidence rate for testicular cancer in Germany.
Earlier discontinuation of TNF‐α inhibitor therapy in female patients with inflammatory bowel disease is related to a greater risk of side effects
Authors: Schultheiss Johannes P.D. , Brand Eelco C. , Lamers Evert , van den Berg Willemijn C.M. , van Schaik Fiona D.M. , Oldenburg Bas , Fidder Herma H. 
Published: July 2019

SummaryBackgroundIn rheumatoid arthritis and psoriasis female sex has been shown to be associated with discontinuation of anti‐tumour necrosis factor‐α (TNF‐α) therapy.AimTo retrospectively assess the association between sex and TNF‐α drug persistence in patients with inflammatory bowel disease (IBD).MethodsAll IBD patients on anti‐TNF‐α therapy with a minimum follow‐up of 12 months in a single tertiary centre were identified. Patient and treatment characteristics and reasons for anti‐TNF‐α discontinuation were recorded. Overall and cause‐specific drug persistence was analysed with Kaplan‐Meier followed by Cox proportional hazards regression models.ResultsWe included 529 patients (49.9% male) with 631 treatment episodes (2280 anti‐TNF‐α treatment years) and 289 discontinuations of therapy. Female sex (adjusted hazard ratio [aHR] 1.42, 95% confidence interval [CI] 1.16‐1.74), greater age at start of therapy per decade (aHR 1.15, 95% CI 1.04‐1.27] and dose escalation (aHR 3.74, 95% CI 2.78‐5.02) were associated with TNF‐α inhibitor discontinuation. Total cohort cause‐specific analysis identified female sex to be associated with side effects (aHR 4.05, 95% CI 2.36‐6.98) but not to other discontinuation reasons. Adalimumab (aHR 1.70, 95% CI 1.11‐2.60) and golimumab (aHR 4.97, 95% CI 2.30‐10.74) use and dose‐escalation (aHR 7.71, 95% CI 5.28‐11.26) were associated with secondary loss of response.ConclusionDrug persistence of anti‐TNF‐α therapy is lower in females as compared to males, mainly because of higher rates of side effects in females. Understanding the sex specific differences in effectiveness and safety of anti‐TNF‐α compounds can aid physicians in clinical decision‐making.
Letter: psoriasiform eruption during vedolizumab therapy
Authors: Garbo Giuseppe Maria , Renna Sara , Caputo Valentina , Orlando Elisabetta , Macaluso Fabio Salvatore , Orlando Rosalba , Bongiorno Maria Rita , Orlando Ambrogio 
Published: July 2019

Linked ContentThis article is linked to Chaparro et al paper. To view these articles, visit https://doi.org/10.1111/apt.15930.
Upsetting the balance on sex selection
Authors: Saunders Ben 
Published: July 2019

AbstractIt is widely assumed that the strongest case for permitting non‐medical sex selection is where parents aim at family balance. This piece criticizes one representative attempt to justify sex selection for family balance. Kluge (2007) assumes that some couples may seek sex selection because they hold discriminatory values, but this need not impugn those who merely have preferences, without evaluative commitments, for a particular sex. This is disputed by those who see any sex selection as inherently sexist because it upholds stereotypes about the sexes. This article takes an alternative approach. I argue that, even if we accept that preference‐based selection is unobjectionable, a policy permitting selection for family balancing does a poor job of distinguishing between value‐based and preference‐based selection. If we wish to permit only preference‐based sex selection we should seek to identify parents’ motives. If we wish to justify a family balancing policy, other arguments are needed.
Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers
Authors: Cipriani Cristiana , Pepe Jessica , Colangelo Luciano , Fassino Valeria , Occhiuto Marco , Biondi Piergianni , Nieddu Luciano , Minisola Salvatore 
Published: July 2019

AbstractObjectiveKidney involvement is a common complication in primary hyperparathyroidism (PHPT). No study so far has assessed the prevalence of kidney injury developing before the reduction in glomerular filtration rate (GFR) in PHPT. The study was aimed at establishing the potential role of biomarkers of kidney injury in detecting subtle renal damage in patients with PHPT.DesignCross‐sectional study.PatientsA total of 69 postmenopausal patients with PHPT and 41 healthy age‐ and sex‐matched subjects were studied. Exclusion criteria were as follows: GFR < 30 mL/min, chronic inflammatory disease, nephrotic syndrome, infection, malignancy, heart failure, recent exposure to iodinated contrast media or nonsteroidal anti‐inflammatory drugs.MeasurementsWe measured a panel of sensitive biomarkers of kidney injury in PHPT vs controls.ResultsMean FGF23 and Klotho were higher in PHPT (72 ± 48 and 811 ± 366 pg/mL, respectively) than controls (53 ± 23.5 and 668.6 ± 17; P < .02 and P < .05). Urine KIM‐1/uCr was significantly higher in PHPT (1.4−6 ± 1.3−6) than controls (9.2−7 ± 7−7; P < .05); this was particularly evident in the CrCl 60‐89 mL/min category (1.36 ± 97 vs 8.2−7 ± 3.6−7; P < .02). Mean values of urine NGAL/uCr were higher in PHPT with (n = 28) compared to those without kidney stones (n = 35; 1.8−5 ± 1.4−5 and 1−5 ± 8−6; P < .0001). We found significant positive associations between urine NGAL/uCr and Ca (R = .292, P < .02) and urine KIM1/uCr and PTH (R = .329, P < .01).ConclusionsWe propose the utilization of these molecules, particularly urine KIM‐1/uCr and urine NGAL/uCr ratios for the assessment of subtle kidney injury in patients with PHPT. These molecules are elevated in tubular necrosis and have potential role in the development of kidney damage in PHPT, according to the severity of the disease.
Unveiling the role of multiple blockholders: Evidence from closely held firms
Authors: Russino Annalisa , Picone Pasquale Massimo , Dagnino Giovanni Battista 
Published: July 2019

AbstractResearch Question/IssueThis paper disentangles how the modes of ownership distribution among multiple blockholders and their heterogeneity shape principal–principal conflicts and, in turn, affect firm performance. The paper offers empirical evidence from a panel of Italian closely held firms over the period 2009–2014.Research Findings/InsightsWe explore the principal–principal conflicts among blockholders across two distinct control structures. When a single blockholder controls the firm, principal–principal conflicts are shaped by the trade‐off between the alignment effect and the monitoring effect. In this scenario, we find that the relationship between the two largest blockholders' ownership concentration and firm performance is U‐shaped. Furthermore, we show that heterogeneity across the two largest blockholder types has a negative effect on performance. In the absence of a controlling blockholder, firm control is usually obtained by forming coalitions, and principal–principal conflicts involve the blockholders inside the controlling coalition and the other shareholders. We find that the ownership distribution and heterogeneity across blockholder types are negatively related to the size of controlling coalitions, and in turn, the size of controlling coalitions is positively correlated with firm performance.Theoretical/Academic ImplicationsWe contribute to principal–principal segment of agency theory by showing that the presence of a controlling blockholder is a key variable that alters the relationship between blockholders' ownership concentration and corporate performance, as well as the relationship between heterogeneity across the largest blockholders and firm performance.Practitioner/Policy ImplicationsOur findings across control structures in which multiple blockholders are present suggest that blockholders take different roles depending on the control structure in which they are involved. The implications of these findings relate to the design of the ownership structure of a firm.
Ductile cast irons: Microstructure influence on the fatigue initiation mechanisms
Authors: Bellini Costanzo , Di Cocco Vittorio , Favaro Gregory , Iacoviello Francesco , Sorrentino Luca 
Published: July 2019

AbstractIn the last decades, the combination of high mechanical performances and low production costs increased the industrial interest on ductile cast irons. These grades are often used for applications where the fatigue resistance can be a critical issue (eg, machine frames for the wind‐power industry or crankshaft used in trucks) and the investigation of the main damaging mechanisms during both the crack initiation and the crack propagation stage could offer new perspectives about these alloys.Ductile cast irons can be considered as a natural composite, being characterized by graphite elements (nodules) embedded in a more or less ductile matrix (ranging from fully ferritic to pearlitic, from martensitic to austempered). In this work, the fatigue crack initiation mechanisms were investigated considering different matrix microstructure and the presence of a mechanical properties gradient in the graphite nodules.
Largely underestimated carbon emission from land use and land cover change in the conterminous United States
Authors: Yu Zhen , Lu Chaoqun , Tian Hanqin , Canadell Josep G. 
Published: July 2019

AbstractCarbon (C) emission and uptake due to land use and land cover change (LULCC) are the most uncertain term in the global carbon budget primarily due to limited LULCC data and inadequate model capability (e.g., underrepresented agricultural managements). We take the commonly used FAOSTAT‐based global Land Use Harmonization data (LUH2) and a new high‐resolution multisource harmonized national LULCC database (YLmap) to drive a land ecosystem model (DLEM) in the conterminous United States. We found that recent cropland abandonment and forest recovery may have been overestimated in the LUH2 data derived from national statistics, causing previously reported C emissions from land use have been underestimated due to the definition of cropland and aggregated LULCC signals at coarse resolution. This overestimation leads to a strong C sink (30.3 ± 2.5 Tg C/year) in model simulations driven by LUH2 in the United States during the 1980–2016 period, while we find a moderate C source (13.6 ± 3.5 Tg C/year) when using YLmap. This divergence implies that previous C budget analyses based on the global LUH2 dataset have underestimated C emission in the United States owing to the delineation of suitable cropland and aggregated land conversion signals at coarse resolution which YLmap overcomes. Thus, to obtain more accurate quantification of LULCC‐induced C emission and better serve global C budget accounting, it is urgently needed to develop fine‐scale country‐specific LULCC data to characterize the details of land conversion.
Comparison of three frailty models and a sarcopenia model in elderly patients with chronic obstructive pulmonary disease
Authors: Hirai Kuniaki , Tanaka Akihiko , Homma Tetsuya , Kaneko Keisuke , Uno Tomoki , Sato Haruna , Manabe Ryo , Ohta Shin , Kusumoto Sojiro , Yamaguchi Fumihiro , Suzuki Shintaro , Sagara Hironori 
Published: July 2019

AimFrailty and sarcopenia affect the prognosis and quality of life of patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain which model is the most suitable for evaluating vulnerability in patients with COPD. We evaluated the validity of three frailty models – the Kihon Checklist (KCL), the Japanese version of the Cardiovascular Health Study and the Study of Osteoporotic Fractures – and one sarcopenia model for older patients with COPD.MethodsThis cross‐sectional study included 201 older (aged ≥65 years) outpatients with COPD. We used three frailty models and one sarcopenia model to identify their correlation with various indices that can evaluate the status of COPD and determine the most ideal model for evaluating vulnerability in patients with COPD.ResultsThe highest prevalence of frailty (38%) and lowest prevalence of robustness (26%) were observed using the KCL. Although all models reflected the characteristics of COPD, the KCL yielded the strongest correlations with clinically important physical, psychological and prognostic indices. The KCL yielded statistically significant differences in almost all indices among the three intergroup comparisons (robust, pre‐frailty and frailty). The KCL was superior in extracting mood disorders to the other models.ConclusionAlthough all investigated models were useful, the KCL was the most suitable for evaluating the frailty status and might enable interventions in patients with COPD. Geriatr Gerontol Int 2019; 19: 896–901.