bluuebunny/crossref_metadata_2025_split huggingface dataset:
659 AN SINGLE-ARM OPEN-LABEL PHASE II STUDY OF CAMRELIZUMAB PLUS APATINIB AS SECOND-LINE TREATMENT FOR ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Wang Feng , Fan Qingxia , Wang Junsheng , Wu Tao , Hong Yonggui , Meng Xiangrui , Ren Zhonghai , Guo Yanzhen , Yang Xiuli , Shi Pei , Yang Jiamei , Yin Xianzhe , Luo Zhiquan , Xia Jin , Zhou Yue , Liu Enjie , Jiang Guozhong 
Published: September 2021

Abstract

Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed.

Methods
This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS.

Results
At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors.

Conclusion
This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.
664 BURDEN OF IN-HOSPITAL CARE IN OESOPHAGEAL CANCER: A NATIONAL POPULATION-BASED STUDY
Authors: Linder Gustav , Klevebro Fredrik , Edholm David , Johansson Jan , Lindblad Mats , Hedberg Jakob 
Published: September 2021

Abstract

Oesophageal cancer management requires extensive in-hospital care. This cohort study aimed to quantify in-hospital care for esophageal cancer patients in relation to intended treatment and to analyze factors associated with risk of spending a large proportion of survival time in hospital.

Methods
All patients with oesophageal cancer in three nationwide registers over a ten-year period, were included. In-hospital care during the first year after diagnosis was evaluated and the proportion of survival time spent in hospital, stratified for intended treatment (curative, palliative or best supportive care) calculated. Associations of relevant factors to a greater proportion of survival time in hospital was analyzed by multivariable logistic regression.

Results
In-hospital care was provided for a median time of 39, 26 and 15 days the first year after diagnosis of oesophageal cancer for curative, palliative and best supportive care groups respectively. Patients receiving curatively intended treatment spent a median of 12% of their survival time in hospital during the first year after diagnosis, while palliative or best supportive care patients spent 19% and 23% respectively. Factors associated with more in-hospital care included higher age, female sex, being unmarried and chronic obstructive pulmonary disease (COPD).

Conclusion
The burden of in-hospital care during the first year after diagnosis of oesophageal cancer was substantial. Important clinical and socioeconomic factors were identified that predisposed to a greater proportion of survival time spent in hospital.
709 PL11.05 NOVEL DIGITAL REFLUX SCINTIGRAPHY DETECTS PULMONARY MICROASPIRATION IN SEVERE GASTRO-OESOPHAGEAL AND LARYNGOPHARYNGEAL REFLUX DISEASE
Authors: Park Jin-soo , Burton Leticia , Van der Wall Hans , Falk Gregory 
Published: September 2021

Abstract

No gold-standard diagnostic test for laryngopharyngeal reflux (LPR) exists. Symptoms alone are non-diagnostic, and pH-impedance studies have poor sensitivity. Pulmonary micro-aspiration is under-recognised in LPR and gastro-oesophageal reflux disease (GORD). The present study aimed to describe the results of a novel digital technique for scintigraphic reflux studies in two groups with severe reflux: those with typical reflux symptoms and those with laryngopharyngeal manifestations of reflux.

Methods
A prospective database of severely symptomatic, treatment-resistant reflux patients was grouped based upon predominant symptom profile of typical GORD or LPR. All patients underwent novel reflux scintigraphy. Results were obtained for early scintigraphic reflux contamination of the pharynx and proximal oesophagus, and delayed contamination of the pharynx and lungs after two hours.

Results
The LPR patients were predominantly female (70.5% vs. 56.1%; p = 0.042) and older than the GORD group (median age 60 years vs. 55.5 years; p = 0.002). Early scintigraphic reflux was seen at the pharynx in 89.2% (GORD 87.7%, LPR 90.4%; p = 0.133), and at the proximal oesophagus in 89.7% (GORD 88.9%, LPR 90.4%; p = 0.147). Delayed contamination of the pharynx was seen in 95.2% (GORD 93.9%, LPR 96.2%; p = 0.468). Delayed pulmonary aspiration was seen in 46% (GORD 36.6%, LPR 53.3%; p = 0.023).

Conclusion
Reflux scintigraphy demonstrated a high rate of digitally identified reflux pulmonary aspiration. Contamination of the proximal oesophagus and pharynx was observed frequently in both groups of severe disease. The likelihood of pulmonary aspiration and potential pulmonary disease needs to be entertained in severe GORD and LPR.
723 TWO- VS. THREE-FIELD LYMPHADENECTOMY FOR ESOPHAGEAL CANCER. A SYSTEMATIC REVIEW AND META-ANALYSIS OF SHORT- AND LONG-TERM OUTCOMES.
Authors: Datrino Letícia Nogueira , Santos Clara Lucato , Tavares Guilherme , Tristão Luca Schiliró , Serafim Maria Carolina Andrade , Orlandini Marina Feliciano , Modesto Victoria Andrade , Tustumi Francisco , Bernardo Wanderley Marques 
Published: September 2021

Abstract

Nowadays, there is still no consensus about the benefits of adding neck lymphadenectomy to the traditional two-fields esophagectomy. An extended lymphadenectomy could potentially increase operation time and the risks for postoperative complications. However, extended lymphadenectomy allows resection of cervical nodes at risk for metastases, potentially increasing long-term survival rates. This study aims to estimate whether cervical prophylactic lymphadenectomy for esophageal cancer influences short- and long-term outcomes through a systematic review of literature and meta-analysis.

Methods
A systematic review was conducted in PubMed, Embase, Cochrane Library Central, and Lilacs (BVS). The inclusion criteria were: (1) studies that compare two-field vs. three-field esophagectomy; (2) adults (&gt;18 years); (3) articles that analyze short- or long-term outcomes; and (4) clinical trials or cohort studies. The results were summarized by forest plots, with effect size (ES) or risk difference (RD) and 95% CI.

Results
Twenty-five articles were selected, comprising 8,954 patients. Three-field lymphadenectomy was associated to higher operation time (ES: -1.51; 95%CI -1.84, −1.18) and higher blood loss (ES: -0.24; 95%CI: −0.37, −0.11). Also, neck lymphadenectomy inputs additional risk for pulmonary complications (RD: 0.03; 95%CI: 0.01, 0.05). No difference was noted for morbidity (RD: 0.01; 95%CI: −0.01, 0.03); leak (−0.02; 95%CI: −0.07, 0.03); postoperative mortality (RD: 0.00; 95%CI: −0.00, 0.01), and hospital stay (ES: -0.05; 95%CI -0.20, 0.10). Three-field lymphadenectomy allowed higher number of retrieved lymph nodes (MD: -1.51; 95%CI -1.84, −1.18), but did not increase the overall survival (HR: 1.11; 95%CI: 0.96, 1.26).

Conclusion
Prophylactic neck lymphadenectomy for esophageal cancer should be performed with caution once it is associated with poorer short-term outcomes compared to traditional two-field lymphadenectomy and does not improve long-term survival. Future esophageal cancer studies should determine the subgroup of patients who could benefit from prophylactic neck lymphadenectomy in long-term outcomes.
847 PREOPERATIVE BRAIN MRI/CT FOR PATIENTS WITH POTENTIALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CANCER, TO BE OR NOT TO BE ROUTINELY?
Authors: Wei Xiufeng , Li Yin , Qin Jianjun , Chen Xiankai , Zhang Ruixiang , Kang Xiaozheng , Xie Hounai , Xu Lei , Yang Yafan 
Published: September 2021

Abstract

There are few prospective studies of brain metastasis from esophageal squamous cell cancer (ESCC). The aim of this study was to investigate the necessity of the brain MRI/CT in the preoperative workup for patients with potentially resectable (cT1-4aN0-3) esophageal squamous cell cancer.

Methods
This was a prospective cross-section clinical trial (ChiCTR1800020304). There were a total of 468 patients who were diagnosed ESCC from October 2018 to August 2020. Of these 468 patients, 385 patients with cT1-4aN0-3 who were potentially candidates for surgical resection were consecutively enrolled into the study. Preoperative brain MRI/CT was performed preoperatively. The treatment regimen could be changed if the brain metastasis was confirmed. The primary endpoint was the incidence rate of the treatment regimen being changed because of brain metastasis.

Results
In all 385 patients, there are only 4 (1%) patients changed their treatment regimen because of brain metastasis proved by MRI/CT. The rate of positive brain MRI/CT findings is 1%. The MRI/CT diagnostic performance for brain metastasis was as follows: sensitivity, 100%; specificity, 100%; positive predictive value, 100%; negative predictive value, 100% and accuracy, 100%. There were no significant difference of bone metastasis among the Age, Sex, Tumor location and clinical stage.

Conclusion
Preoperative brain MRI/CT might help identify brain metastases in patients with esophageal cancer, but we do not recommend the brain MRI/CT in the preoperative workup for patients with potentially resectable esophageal squamous cell cancer.
Conditions to Terminate Reproductive Diapause of a Univoltine Insect:Ceratapion basicorne(Coleoptera: Apionidae), a Biological Control Agent of Yellow Starthistle
Authors: Smith Lincoln , Park Ikju 
Published: September 2021

AbstractCeratapion basicorne (Illiger) is a recently approved univoltine biological control agent that develops inside the rosette of yellow starthistle (Centaurea solstitialis L.), an invasive annual plant. Adult weevils normally emerge in early summer, and females are thought to be in reproductive diapause until the following spring, when they oviposit in rosettes. The long period of reproductive diapause constrains mass-rearing this weevil because only one generation per year can be produced. Determining the environmental conditions that regulate diapause termination may enable shortening diapause under laboratory conditions to increase production of adults to release. We tested three hibernating conditions (greenhouse [ambient temperature and photoperiod], glass door refrigerator [5°C and ambient photoperiod], and growth chamber [5°C and 24 h dark]) for three durations (4, 8, 11 wk). The highest proportion of females laying eggs came from the growth chamber, with 40% terminating diapause after 4 wk, 80% after 8 wk, and 95% after 11 wk of exposure. Our study demonstrates that duration of cold temperature is an important stimulus to terminate reproductive diapause of C. basicorne, and that exposure to ambient light had no effect at 5°C. However, 47% of females held at ambient greenhouse conditions, without any chilling period, completed diapause within 11 wk. Thus, a cold period can accelerate diapause development, but it is not necessary for its completion. Reducing the winter diapause period from about 6 mo to 11 wk should enable the production of multiple generations per year to increase the number of insects available to release.
An adolescent with Behçet’s aortitis mimicking infective endocarditis: a case report
Authors: Hattori Kaoru , Tabata Mimiko , Nojiri Tohru , Kurata Atsushi 
Published: September 2021

Abstract

Background
Aortic valve involvement is rare in patients with Behçet’ s disease (BD); however, recurrent prosthetic valve detachment after valve surgery has frequently been reported. We report a rare case of Behçet’s aortitis involving the aortic valve, mimicking active infective endocarditis (IE) with perivalvular abscess.

Case summary
A 16-year-old boy, with an unknown case of BD, presented with pyrexia of unknown origin, severe aortic valve regurgitation, vegetation, and perivalvular abscess in the aortic valve. All cultures tested negative for microorganisms. As we suspected IE, aortic valve replacement was performed. After the initial surgery, recurrent prosthetic valve detachment and pseudoaneurysm formation occurred, which resulted in the diagnosis of BD. The patient underwent a modified Bentall procedure, in which the valve conduit was proximally sutured to the left ventricular outflow tract instead of the aortic annulus. Immunosuppressive therapy was initiated on the 10th postoperative day. His condition became stable, and additional surgery was not required.

Discussion
The echocardiographic findings of Behçet’s aortitis involving the aortic valve resemble those of aortic valve IE. Modified Bentall procedure, combined with effective immunosuppressive therapy, may be useful in preventing prosthetic valve detachment.
Robust Cre recombinase activity in the biotrophic smut fungus Ustilago maydis enables efficient conditional null mutants in planta
Authors: de la Torre Antonio , Jurca Matteo , Hoffmann Kai , Schmitz Lara , Heimel Kai , Kämper Jörg , Pérez-Martín José 
Published: September 2021

Abstract
Site-specific recombinases have been used in higher eukaryotes, especially in animals, for a broad range of applications, including chromosomal translocations, large deletions, site-specific integration, and tissue-specific as well as conditional knock-outs. The application of site-specific recombination has also been demonstrated in simple eukaryotes like fungi and protozoa. However, its use in fungal research, especially in phytopathogenic fungi, has often been limited to “recycle” the marker genes used in transformation experiments. We show that Cre recombinase can be used for conditional gene deletions in the phytopathogenic fungus Ustilago maydis. Conditional gene knock-outs can be generated via the transcriptional control of the recombinase by U. maydis promoters specifically activated during the biotrophic phase of fungal growth, enabling gene deletions at defined developmental stages inside the plant tissue. Also, we show that a tamoxifen-activated Cre-recombinase allows the tight control necessary for the induced deletion of essential genes by the addition of tamoxifen. These tools will be helpful to address the function of genes under both axenic and in planta conditions for the U. maydis-maize pathosystem and should pave the way for similar approaches in other plant pathosystems.
ISA API: An open platform for interoperable life science experimental metadata
Authors: Johnson David , Batista Dominique , Cochrane Keeva , Davey Robert P , Etuk Anthony , Gonzalez-Beltran Alejandra , Haug Kenneth , Izzo Massimiliano , Larralde Martin , Lawson Thomas N , Minotto Alice , Moreno Pablo , Nainala Venkata Chandrasekhar , O'Donovan Claire , Pireddu Luca , Roger Pierrick , Shaw Felix , Steinbeck Christoph , Weber Ralf J M , Sansone Susanna-Assunta , Rocca-Serra Philippe 
Published: September 2021

Abstract

Background
The Investigation/Study/Assay (ISA) Metadata Framework is an established and widely used set of open source community specifications and software tools for enabling discovery, exchange, and publication of metadata from experiments in the life sciences. The original ISA software suite provided a set of user-facing Java tools for creating and manipulating the information structured in ISA-Tab—a now widely used tabular format. To make the ISA framework more accessible to machines and enable programmatic manipulation of experiment metadata, the JSON serialization ISA-JSON was developed.

Results
In this work, we present the ISA API, a Python library for the creation, editing, parsing, and validating of ISA-Tab and ISA-JSON formats by using a common data model engineered as Python object classes. We describe the ISA API feature set, early adopters, and its growing user community.

Conclusions
The ISA API provides users with rich programmatic metadata-handling functionality to support automation, a common interface, and an interoperable medium between the 2 ISA formats, as well as with other life science data formats required for depositing data in public databases.
Reproductive aging and menopause-like transition in the menstruating spiny mouse (Acomys cahirinus)
Authors: Bellofiore Nadia , George Evgenia , Vollenhoven Beverley , Temple-Smith Peter 
Published: September 2021

AbstractSTUDY QUESTIONDoes the naturally menstruating spiny mouse go through menopause?SUMMARY ANSWEROur study is the first to show a natural and gradual menopausal transition in a rodent.WHAT IS KNOWN ALREADYAge-related depletion of the human ovarian reserve (OvR) leads to menopause, the permanent cessation of menstruation and reproduction. Current rodent models of menopause are inappropriate for inferences of the human condition, as reproductive senescence is abrupt or induced through ovariectomy. The spiny mouse is the only confirmed rodent with a naturally occurring menstrual cycle.STUDY DESIGN, SIZE, DURATIONHistological assessment of virgin spiny mice occurred in females aged 6 months (n = 14), 1 year (n = 7), 2 years (n = 13), 3 years (n = 9) and 4 years (n = 9). Endocrinology was assessed in a further 9 females per age group. Five animals per group were used for ovarian stereology with additional ovaries collected at prenatal Day 35 (n = 3), day of birth (n = 5), postnatal Days 35 (n = 5) and 100 (n = 5) and 15 months (n = 5).PARTICIPANTS/MATERIALS, SETTING, METHODSMorphological changes in the reproductive system were examined using hematoxylin and eosin stains. Proliferating cell nuclear antigen immunohistochemistry assessed endometrial proliferation and sex steroids estradiol and testosterone were assayed using commercial ELISA kits.MAIN RESULTS AND THE ROLE OF CHANCEThe proportion of females actively cycling was 86% at 6 months, 71% at 1 year, 69% at 2 years, 56% at 3 years and 44% at 4 years. Uterine and ovarian weights declined steadily from 1 year in all groups and corresponded with loss of uterine proliferation (P &lt; 0.01). Estradiol was significantly decreased at 1 and 2 years compared to 6-month-old females, before becoming erratic at 3 and 4 years, with no changes in testosterone across any age. Fully formed primordial follicles were observed in prenatal ovaries. Aging impacted on both OvR and growing follicle numbers (P &lt; 0.001–0.0001). After the age of 3 years, the follicle decline rate increased more than 5-fold.LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONThis is a descriptive study in a novel research rodent whereby reagents validated for use in the spiny mouse were limited.WIDER IMPLICATIONS OF THE FINDINGSThe gradual, rather than sudden, menopausal transition suggests that the spiny mouse is a more appropriate perimenopausal model than the current rodent models in which to examine the neuroendocrine pathways that encompass all hormonal interactions in the hypothalamic–pituitary–gonadal axis. The logistic, ethical and economic advantages of such a model may reduce our reliance on primates in menopause research and enable more thorough and invasive investigation than is possible in humans.STUDY FUNDING/COMPETING INTEREST(S)Hudson Institute is supported by the Victorian State Government Operational Infrastructure Scheme. The authors declare no competing interests.
Emotions and the German Peasants’ War of 1524–6
Authors: Roper Lyndal 
Published: September 2021

Abstract
This article addresses the questions of the history of emotions to the German Peasants' War of 1524-5. The biggest popular uprising in Western Europe before the French Revolution, it overturned lordship in wide areas of Germany and beyond for about three months. It transformed the character of the Reformation as Luther condemned the peasant rebels. The revolt followed an emotional arc, shaped as much by the seasons as it was by the logic of revolution. The article argues that historians need to understand emotions and emotional cycles to understand how revolutions begin and unfold.
Recreational fishers’ perceptions of climate change
Authors: Ryan Karina L , Shaw Jenny , Tracey Sean R , Lyle Jeremy M 
Published: September 2021

Abstract
Shifts in marine species distributions associated with climate change occur across large spatial areas and long time periods. Marine recreational fishing occurs in most countries with many participants interacting regularly with the environment, yet there have been few studies on the views of recreational fishers towards climate change. This study aims to assess perceptions of climate change for a boat-based recreational fishery in Western Australia, where fishing occurs across a wide latitudinal range, from tropical to temperate waters. Perceptions of climate change were assessed by fisher demographics and fishing behaviour. One in two respondents noticed changes in species types and distributions, with metropolitan residents and avid fishers more likely to notice these changes. Two out of three respondents considered climate change is occurring, recognition of which was higher amongst metropolitan residents, females, and younger respondents. Males and older respondents, on the other hand considered themselves to have more knowledge of climate change science. This study provides a baseline to assist in informing policy changes that might be required to address the impacts of climate change. Studies of this kind can also build support for citizen science programs to enhance data collection across the spatial and temporal time scales required to observe climate change.