bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults
Authors: Cowling Benjamin J , Thompson Mark G , Ng Tiffany W Y , Fang Vicky J , Perera Ranawaka A P M , Leung Nancy H L , Chen Yuyun , So Hau Chi , Ip Dennis K M , Iuliano A Danielle 
Published: May 2020

Abstract

Background
We analyzed data from a randomized controlled trial on the reactogenicity of 3 enhanced influenza vaccines compared with standard-dose (SD) inactivated influenza vaccine.

Methods
We enrolled community-dwelling older adults in Hong Kong, and we randomly allocated them to receive 2017–2018 northern hemisphere formulations of SD vaccine (FluQuadri; Sanofi Pasteur), MF59-adjuvanted vaccine (FLUAD; Seqirus), high-dose (HD) vaccine (Fluzone High-Dose; Sanofi Pasteur), or recombinant hemagglutinin vaccine (Flublok; Sanofi Pasteur). Local and systemic reactions were evaluated at days 1, 3, 7, and 14 after vaccination.

Results
Reported reactions were generally mild and short-lived. Systemic reactions occurred in similar proportions of participants by vaccine. Some local reactions were slightly more frequently reported among recipients of the MF59-adjuvanted and HD vaccines than among SD vaccine recipients. Participants reporting feverishness 1 day after vaccination had mean fold rises in postvaccination hemagglutination inhibition titers that were 1.85-fold higher (95% confidence interval, 1.01–3.38) for A(H1N1) than in those who did not report feverishness.

Conclusions
Some acute local reactions were more frequent after vaccination with MF59-adjuvanted and HD influenza vaccines, compared with SD inactivated influenza vaccine, whereas systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population.

Clinical Trials Registration
NCT03330132.
High Risk of Clinical Relapse in Patients With Chronic Hepatitis B Virus Infection After Cessation of Prophylactic Antiviral Therapy for Rituximab-Containing Chemotherapy
Authors: Chang Wei-Yuan , Chiu Yen-Cheng , Chiu Fang-Wei , Hsu Yao-Chun , Tseng Tai-Chung , Cheng Pin-Nan , Yang Sheng-Shun , Liu Chun-Jen , Su Tung-Hung , Yang Hung-Chih , Liu Chen-Hua , Chen Pei-Jer , Chen Ding-Shinn , Kao Jia-Horng 
Published: May 2020

Abstract

Background
Prophylaxis with nucleos(t)ide analogue (NA) is recommended to prevent hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)–positive patients receiving rituximab-based B-cell depletion therapy. However, little is known about the risk of clinical relapse after withdrawal of NA.

Methods
We retrospectively analyzed 77 noncirrhotic HBsAg carriers with hematological cancer who received rituximab-containing chemotherapy. All of them received either prophylactic entecavir or tenofovir therapy. The risk of clinical relapse and hepatic decompensation after cessation of NA was explored.

Results
Clinical relapse and hepatic decompensation developed in 25 (32.5 %) and 11 (14.3 %) of the patients, respectively, and 2 patients died of hepatic decompensation. Most of the hepatic events occurred within 1 year (20 of 25; 80.0%) after stopping NA. A higher pretreatment viral load (≥2000 vs &lt;2000 IU/mL) was associated with increased risks of clinical relapse (hazard ratio, 3.47; 95% confidence interval, 1.56–7.73) and hepatic decompensation (9.91; 2.14–45.92). Of 51 patients with pretreatment viral load &lt;2000 IU/mL, clinical relapse occurred in 10 (19.6 %) and hepatic decompensation in 2 (3.9%).

Conclusions
Pretreatment HBV DNA ≥2000 IU/mL is associated with increased risk of liver-related disease after cessation of prophylactic NA therapy in patients who received rituximab-containing chemotherapy.
Mating Disruption of Chilo suppressalis From Sex Pheromone of Another Pyralid Rice Pest Cnaphalocrocis medinalis (Lepidoptera: Pyralidae)
Authors: Liang Yu-yong , Luo Mei , Fu Xiao-gang , Zheng Li-xia , Wei Hong-yi 
Published: May 2020

Abstract
The rice stem borer, Chilo suppressalis (Walker), and the rice leaf folder, Cnaphalocrocis medinalis Guenée, are two of the most destructive lepidopteran pests in rice. Since these two pyralid insects overlap in their occurrence in rice paddy fields, farmers prefer to set their pheromone-baited traps together in the rice fields for their monitoring. However, our field observation demonstrated that no male adult of C. suppressalis was captured in traps baited with commercial sex pheromone of C. suppressalis (CCS) combined with commercial sex pheromone of C. medinalis (CCM). To confirm that the C. medinalis sex pheromone component(s) interfere with the attraction of males of the rice stem borers to their conspecific females, single components of C. medinalis sex pheromone combined with CCS in traps were tested in the laboratory and rice paddy field. The results revealed that the two alcohol components in CCM, i.e., (Z)-11-octadecen-1-ol (Z11-18: OH) and (Z)-13-octadecen-1-ol (Z13-18: OH) may cause a significant reduction in capturing C. suppressalis males caused by CCS. We recommend against using these sex pheromones together in the field and suggest that Z11-18: OH and Z13-18: OH could be potential inhibitors or antagonists of C. suppressalis sex pheromone to control the rice stem borer.
Accelerated partial breast irradiation by brachytherapy: present evidence and future developments
Authors: Galalae Razvan , Hannoun-Lévi Jean-Michel 
Published: May 2020

Abstract
Accelerated partial breast irradiation (APBI) delivers a short course of adjuvant RT after breast conserving surgery to only a limited part of the breast where the tumor was located. This procedure requires expertise, good communication, and close collaboration between specialized surgeons and attending radiation oncologists with adequate intraoperative tumor bed clip marking. However, APBI offers several intrinsic benefits when compared with whole breast irradiation (WBIR) including reduced treatment time (1 versus 4–6 weeks) and better sparing of surrounding healthy tissues. The present publication reviews the APBI level 1-evidence provided with various radiation techniques supplemented by long-term experience obtained from large multi-institutional phase II studies. Additionally, it offers an outlook on recent research with ultra-short or single-fraction APBI courses and new brachytherapy sources. Mature data from three randomized controlled trials (RCTs) clearly prove the noninferiority of APBI with ‘only two techniques—1/MIBT (multicatheter interstitial brachytherapy) (two trials) and 2/intensity modulated radiotherapy (one trial)’—in terms of equivalent local control/overall survival to the previous standard ‘conventionally fractionated WBIR’. However, MIBT-APBI techniques were superior in both toxicity and patient-reported outcomes (PROs) versus WBIR at long-term follow-up. Currently, in RCT-setting, alternative APBI techniques such as intraoperative electrons, 50-kV x-rays and three-dimensional conformal external beam radiotherapy (3D-CRT) failed to demonstrate noninferiority to conventionally fractionated WBIR. However, 3D-CRT-APBI compared noninferior to hypo-fractionated WBIR in preventing ipsilateral breast tumor recurrence (randomized RAPID-trial) but was associated with a higher rate of late radiation toxicity. Ultimately, MIBT remains the only APBI modality with noninferior survival/superior toxicity/PROs at 10-years and therefore should be prioritized over alternative methods in patients with breast cancer considered at low-risk for local recurrence according to recent international guidelines.
Clinical significance of tumour mutation burden in immunotherapy across multiple cancer types: an individual meta-analysis
Authors: Yang Zhenyu , Wei Shiyou , Deng Yulan , Wang Zihuai , Liu Lunxu 
Published: May 2020

Abstract

Background
Biomarkers for stratifying patients that could benefit from immune checkpoint inhibitors are necessary. Tumour mutation burden has recently become a promising biomarker in cancer, but the associations between tumour mutation burden and outcomes of immune checkpoint inhibitors treatment were not well-documented in present studies.

Methods
We searched PubMed, Web of Science and EMBASE databases up to 1 October 2019. Studies evaluated the association between tumour mutation burden and clinical outcomes were included. Hazard ratios and odds ratios were applied to estimate the association of tumour mutation burden score with overall survival, progression-free survival and response rate, respectively. The best cut-off value was chosen by best discriminated overall survival using Contal and O’Quigley method.

Results
Twenty-two studies involving 6171 patients in diverse cancers were included. The individual participant data meta-analysis demonstrated that high tumour mutation burden was associated with better overall survival (HR = 0.57, 95% CI = 0.50–0.64) and progression-free survival (HR = 0.50, 95% CI = 0.40–0.63) and higher response rate. The best cut-off values in each cancer type were 17.7/MB in non-small cell lung cancer, 7.9/MB in bladder cancer, 6.1/MB in melanoma, 12.3/MB in colorectal cancer, 6.9/MB in esophagogastric cancer, 10.5/MB in head and neck cancer. The pooled meta-analysis showed the prognosis value was robust and the sensitivity, specificity and area under the receiver operating characteristic curves in predicting response rates were 0.63, 0.71 and 0.73, respectively.

Conclusions
The present meta-analysis indicates tumour mutation burden is a promising predictor of immune checkpoint inhibitors therapy but the cut-off value differs in different cancers.
Quality of Life With Pembrolizumab for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: KEYNOTE-040
Authors: Harrington Kevin J , Soulières Denis , Le Tourneau Christophe , Dinis Jose , Licitra Lisa F , Ahn Myung-Ju , Soria Ainara , Machiels Jean-Pascal H , Mach Nicolas , Mehra Ranee , Burtness Barbara , Ellison Misoo C , Cheng Jonathan D , Chirovsky Diana Romana , Swaby Ramona F , Cohen Ezra E W 
Published: May 2020

Abstract

Background
Head and neck squamous cell carcinoma (HNSCC) affects health-related quality of life (HRQoL); few treatments have demonstrated clinically meaningful HRQoL benefit. KEYNOTE-040 evaluated pembrolizumab vs standard of care (SOC) in patients with recurrent and/or metastatic HNSCC whose disease recurred or progressed after platinum-containing regimen.

Methods
Patients received pembrolizumab 200 mg or SOC (methotrexate, docetaxel, or cetuximab). Exploratory HRQoL analyses used European Organisation for Research and Treatment of Cancer (EORTC) 30 quality-of-life, EORTC 35-question quality-of-life head and neck cancer-specific module, and EuroQoL 5-dimensions questionnaires.

Results
The HRQoL population comprised 469 patients (pembrolizumab = 241, SOC = 228). HRQoL compliance for patients in the study at week 15 was 75.3% (116 of 154) for pembrolizumab and 74.6% (85 of 114) for SOC. The median time to deterioration in global health status (GHS) and QoL scores were 4.8 months with pembrolizumab and 2.8 months with SOC (hazard ratio = 0.79, 95% confidence interval [CI] = 0.59 to 1.05). At week 15, GHS / QoL scores were stable for pembrolizumab (least squares mean [LSM] = 0.39, 95% CI = –3.00 to 3.78) but worsened for SOC (LSM = −5.86, 95% CI = −9.68 to −2.04); the LSM between-group difference was 6.25 points (95% CI = 1.32 to 11.18; nominal 2-sided P = .01). A greater difference in the LSM for GHS / QoL score occurred with pembrolizumab vs docetaxel (10.23, 95% CI = 3.15 to 17.30) compared with pembrolizumab vs methotrexate (6.21, 95% CI = −4.57 to 16.99) or pembrolizumab vs cetuximab (−1.44, 95% CI = −11.43 to 8.56). Pembrolizumab-treated patients had stable functioning and symptoms at week 15, with no notable differences from SOC.

Conclusions
GHS / QoL scores were stable with pembrolizumab but declined with SOC in patients at week 15, supporting the clinically meaningful benefit of pembrolizumab in recurrent and/or metastatic HNSCC.
Prostate Cancer Incidence 5 Years After US Preventive Services Task Force Recommendations Against Screening
Authors: Jemal Ahmedin , Culp MaryBeth B , Ma Jiemin , Islami Farhad , Fedewa Stacey A 
Published: May 2020

Abstract

Background
Previous studies reported that prostate cancer incidence rates in the United States declined for local-stage disease and increased for regional- and distant-stage disease following the US Preventive Services Task Force recommendations against prostate-specific antigen-based screening for men aged 75 years and older in 2008 and for all men in 2012. It is unknown, however, whether these patterns persisted through 2016.

Methods
Based on the US Cancer Statistics Public Use Research Database, we examined temporal trends in invasive prostate cancer incidence from 2005 to 2016 in men aged 50 years and older stratified by stage (local, regional, and distant), age group (50-74 years and 75 years and older), and race and ethnicity (all races and ethnicities, non-Hispanic Whites, and non-Hispanic Blacks) with joinpoint regression models to estimate annual percent changes. Tests of statistical significance are 2-sided (P &lt; .05).

Results
For all races and ethnicities combined, incidence for local-stage disease declined beginning in 2007 in men aged 50-74 years and 75 years and older, although the decline stabilized during 2013-2016 in men aged 75 years and older. Incidence decreased by 6.4% (95% CI = 4.9%-9% to 7.9%) per year from 2007 to 2016 in men aged 50-74 years and by 10.7% (95% CI = 6.2% to 15.0%) per year from 2007 to 2013 in men aged 75 years and older. In contrast, incidence for regional- and distant-stage disease increased in both age groups during the study period. For example, distant-stage incidence in men aged 75 years and older increased by 5.2% (95% CI = 4.2% to 6.1%) per year from 2010 to 2016.

Conclusions
Regional- and distant-stage prostate cancer incidence continue to increase in the United States in men aged 50 years and older, and future studies are needed to identify reasons for the rising trends.
Overall Survival of CDK4/6-Inhibitor–Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis
Authors: Schettini Francesco , Giudici Fabiola , Giuliano Mario , Cristofanilli Massimo , Arpino Grazia , Del Mastro Lucia , Puglisi Fabio , De Placido Sabino , Paris Ida , De Placido Pietro , Venturini Sergio , De Laurentis Michelino , Conte PierFranco , Juric Dejan , Llombart-Cussac Antonio , Pusztai Lajos , Prat Aleix , Jerusalem Guy , Di Leo Angelo , Generali Daniele 
Published: May 2020

Abstract

Background
Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors + endocrine therapy (ET) prolonged progression-free survival as first- or second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer prognosis. Given the recent publication of overall survival (OS) data for the 3 CDK4/6-inhibitors, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups.

Methods
We conducted a systematic literature search to select all available phase II or III randomized clinical trials of CDK4/6-inhibitors + ET reporting OS data in first- or second-line therapy of HR+/HER2-negative pre- or postmenopausal metastatic breast cancer. A random effect model was applied for the analyses. Heterogeneity was assessed with I2statistic. Subgroup analysis was performed to explore the effect of study-level factors. The project was registered in the Open Science Framework database (doi: 10.17605/OSF.IO/TNZQP).

Results
Six studies were included in our analyses (3421 patients). A clear OS benefit was observed in patients without (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.54 to 0.85, I2 = 0.0%) and with visceral involvement (HR = 0.76, 95% CI = 0.65 to 0.89, I2 = 0.0%), with at least 3 metastatic sites (HR = 0.75, 95% CI = 0.60 to 0.94, I2 = 11.6%), in an endocrine-resistant (HR = 0.79, 95% CI = 0.67 to 0.93, I2 = 0.0%) and sensitive subset (HR = 0.73, 95% CI = 0.61 to 0.88, I2 = 0.0%), for younger than 65 years (HR = 0.80, 95% CI = 0.67 to 0.95, I2 = 0.0%) and 65 years or older (HR = 0.71, 95% CI = 0.53 to 0.95, I2 = 44.4%), in postmenopausal (HR = 0.76, 95% CI = 0.67 to 0.86, I2 = 0.0%) and pre- or perimenopausal setting (HR = 0.76, 95% CI = 0.60 to 0.96, I2 = 0.0%) as well as in chemotherapy-naïve patients (HR = 0.72, 95% CI = 0.55 to 0.93, I2 = 0.0%).

Conclusions
CDK4/6-inhibitors + ET combinations compared with ET alone improve OS independent of age, menopausal status, endocrine sensitiveness, and visceral involvement and should be preferred as upfront therapy instead of endocrine monotherapy.
Excessive Weight Gain Associated With Dolutegravir Initiation in a 10-Year-Old Female With Perinatally Acquired Human Immunodeficiency Virus: A Case Report and Review of the Literature
Authors: Li J , Yusuf E H , Agwu A L 
Published: May 2020

Abstract
Children with perinatally acquired human immunodeficiency virus (PHIV) face a lifetime of combination antiretroviral treatment that often includes dolutegravir (DTG). DTG, an integrase strand inhibitor that has been linked to weight gain in adults, is increasingly being used in children. Understanding its potential short- and long-term sequelae in children is critically important. We report a case of excessive weight gain in a child with PHIV on DTG and provide a brief literature review.
An evolutionary view of melatonin synthesis and metabolism related to its biological functions in plants
Authors: Tan Dun-Xian , Reiter Russel J 
Published: May 2020

AbstractPlant melatonin research is a rapidly developing field. A variety of isoforms of melatonin’s biosynthetic enzymes are present in different plants. Due to the different origins, they exhibit independent responses to the variable environmental stimuli. The locations for melatonin biosynthesis in plants are chloroplasts and mitochondria. These organelles have inherited their melatonin biosynthetic capacities from their bacterial ancestors. Under ideal conditions, chloroplasts are the main sites of melatonin biosynthesis. If the chloroplast pathway is blocked for any reason, the mitochondrial pathway will be activated for melatonin biosynthesis to maintain its production. Melatonin metabolism in plants is a less studied field; its metabolism is quite different from that of animals even though they share similar metabolites. Several new enzymes for melatonin metabolism in plants have been cloned and these enzymes are absent in animals. It seems that the 2-hydroxymelatonin is a major metabolite of melatonin in plants and its level is ~400-fold higher than that of melatonin. In the current article, from an evolutionary point of view, we update the information on plant melatonin biosynthesis and metabolism. This review will help the reader to understand the complexity of these processes and promote research enthusiasm in these fields.
Political Risk
Authors: Rubins Noah D , Papanastasiou Thomas-Nektarios , Kinsella N Stephan 
Published: May 2020

Abstract
This chapter discusses the types of political risk that foreign investors are likely to encounter, the factors that contribute to political risk, and some practical steps that investors might take to measure political risks in a particular State before investing capital. For investors concerned with political risk, the primary distinction to be made is between detriment (loss) proximately caused by the host State or its agents, and that caused by the commercial realities of supply and demand, or by natural disasters. This line is far harder to draw in practice than in theory: the scenarios investors face in carrying out a long-term business project on foreign soil are complex and affected by a range of factors, both within and outside government control.
Courting Failure
Authors: Milanović Marko 
Published: May 2020

Abstract
This chapter asks whether international tribunals are capable of healing a traumatized society. In that sense, it is not enough that a tribunal punish the guilty, it must also produce a social awakening concerning the community’s own culpability for the wrongdoing. Drawing on an empirical evaluation of the social response to the work of the International Criminal Tribunal for the former Yugoslavia (ICTY), the chapter questions whether this can occur. At least in the case of the ICTY—otherwise regarded as one of the most successful international tribunals—the work of the Tribunal has been shockingly ineffective because some sectors of the public simply refuse to accept the conclusions that the Tribunal has drawn. The chapter then broadens this conclusion into a general theory: that the work of a tribunal will be viewed positively by the local population unless the Tribunal is a threat to local elites who have the power to shape public opinion against the Tribunal.
The Two Cultures of International Criminal Law
Authors: d’Aspremont Jean 
Published: May 2020

Abstract
This chapter looks more globally at the methodologies used by international criminal justice, particularly its tendency towards expansionism: including more actors, more situations, and more offences under its umbrella. It does more than simply tell the story of this expansion; this chapter also systematizes it in an important way. The chapter argues that international criminal justice’s expansionism has taken two important forms. The first wave involved a sources-based expansionism, characterized by the field’s desire to expand its influence by increasing the number of legal sources—treaty, custom, general principles—that could be sources of international criminal law. But when that process was largely complete, the passage of the Rome Statute of the International Criminal Court heralded a new, hermeneutic form of expansionism—this one based on interpretation rather than on adding new sources of law. While the hermeneutic expansion is less overt and less recognized than the first wave, its consequences are still dramatic.
Historical Reasoning and Judicial Historiography in International Criminal Trials
Authors: Priemel Kim Christian 
Published: May 2020

Abstract
This chapter explores the overlaps and differences between historical reasoning and judicial historiography. It takes the reader from Nuremberg to the International Criminal Court to show that judicial proceedings have been a major site for the development of both micro- and macro-level histories, sometimes problematically so. The chapter addresses if, how, and to what extent macro-historical interpretations permeated the high-profile proceedings at Nuremberg and Tokyo and helps explain their dynamics and outcomes. This pattern was repeated in domestic trials of Nazi-era crimes throughout the post-war decades, yet largely overlooked in the creation and day-to-day operations of the ad hoc tribunals that sprang to life in the 1990s and early 2000s. To conclude, the chapter suggests that this unawareness may explain some of the Tribunals’ shortcomings and needs to be reflected by both lawyers and historians if the ICC is to avoid even more criticism than that levelled against it since its inception.