bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCT04552223: A phase II study of nivolumab plus BMS-986016 (relatlimab) in patients with metastatic uveal melanoma (UM) (CA224-094).
Authors: Lutzky Jose , Feun Lynn G. , Magallanes Norma , Kwon Deukwoo , Harbour J. William 
Published: June 2021

TPS9590 Background: Uveal melanoma (UM) is a rare disease but 50% of patients will eventually develop metastatic disease, for which not effective therapy is available. Liver-directed therapies, immunotherapy, targeted therapy and chemotherapy have limited activity [1]. Lymphocyte activation gene 3(LAG-3) is an immune checkpoint receptor associated with decreased T-cell effector function and tumor escape. Preclinical models have shown that dual inhibition of LAG-3 and PD-1 blockade generates synergistic anti-tumor activity [2]. Recent preclinical data indicates that uveal melanoma CD8+ T cells express the checkpoint receptor LAG3 to a greater extent than PD1 or CTLA4 [3,4]. Therefore, LAG3 is a potential candidate for checkpoint inhibitor immunotherapy in UM. Relatlimab is a human LAG-3-specific antibody isolated from immunized transgenic mice which binds to a defined epitope on LAG-3 with high affinity and specificity and potently blocks the interaction of LAG-3 with its ligand, MHC Class II. Methods: This is an open-label, single arm, single site investigator-initiated phase II study, NCT04552223. Based on Simon two-stage minimax design, 13 patients will be enrolled in Stage 1. If at least one response is noted, the study will proceed to Stage 2 and enroll an additional 14 patients. The null hypothesis will be rejected if 4 or more responses are observed among 27 patients. This design achieves 5% type I error and 80% power when the true ORR is 20%. The trial opened to accrual in December 2020. As of February 15, 2021 four patients had been enrolled the first stage of accrual. Main eligibility criteria include patients with biopsy proven metastatic uveal melanoma, previously untreated with PD-1, CTLA-4 and/or LAG-3 blocking antibodies and in good performance status. Enrolled patients are treated in the outpatient setting. Nivolumab 480 mg is mixed in the same bag with relatlimab 160 mg and administered intravenously over 60 minutes every 4 weeks until disease progression or intolerable toxicity for up to 24 months. The primary endpoint is best objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), median duration of response (mDOR), and adverse events (AEs). Correlative studies will evaluate pre- and post-treatment characteristics of T cells in the tumor microenvironment and blood. Clinical trial information: NCT04552223.
Phase I/II trial of intratumoral administration of hu14.18-IL2, with local radiation, nivolumab, and ipilimumab in subjects with advanced melanoma.
Authors: Albertini Mark R. , Morris Zachary Scott , Hank Jacquelyn A , Ranheim Erik , Zuleger Cindy L , McDowell Kimberly , Quale Renae M , Monson Molly , Clements Erin , Koehn Tamara , Neuman Heather B. , Weber Sharon M. , Racz Jennifer , Henry Mary Beth , Reinstad Emily , Kim KyungMann , Gillies Stephen D. , Sondel Paul M. 
Published: June 2021

TPS9591 Background: We are studying an intratumoral (IT) in situ vaccine strategy using the GD2-reactive hu14.18-IL2 immunocytokine (hu-IC) to convert the injected tumor into a site of enhanced tumor antigen presentation, as has been shown in mice. Hu-IC is a humanized monoclonal antibody (mAb) covalently linked to two molecules of IL-2 at the Fc region. The hu14.18 mAb recognizes GD2, a disialoganglioside found in tumors of neuroectodermal origin. We previously studied intravenous (IV) hu-IC and reported immune activation and reversible toxicities (1). Surgery to resect recurrent stage III or stage IV melanoma combined with 3 courses of IV hu-IC resulted in prolonged tumor-free survival in some patients (2). Murine GD2+ tumor models showed enhanced antitumor activity and recruitment of T cells using hu-IC IT versus IV (3). In these models, the combination of radiation therapy (RT) followed by IT hu-IC dramatically potentiates the antitumor response and enhanced response to immune checkpoint blockade (4). Biological samples (blood and tumor) will be interrogated to identify biological mechanisms and develop biomarkers for future testing. Methods: This outpatient phase I/II trial uses a 3 + 3 design to determine maximum tolerated or maximum administered dose of IT hu-IC (planned dose level: 2 mg/m2/day; de-escalation dose level: 1 mg/m2/day) when given alone (Phase 1A: 3-12 patients), after RT (Phase 1B: 6-12 patients), after RT and in combination with nivolumab (Phase 1C: 6-12 patients), and after RT and in combination with nivolumab and ipilimumab (Phase 1D: 31-34 patients). The trial will evaluate safety, antitumor activity, and immunologic endpoints and includes an expanded Phase II cohort (Phase 1D). The IT injections (once daily x 3 days) are delivered every 21 days for 4 cycles and can then continue every 28 days for up to 13 cycles if there is response/stable disease and residual injectable tumor. Key inclusion criteria: 1) histologically proven, malignant melanoma that is advanced (Stage IV) or surgically incurable; 2) at least 1 (preferably 2) sites of disease amenable to safe repeated IT injections; and 3) must have received or declined at least one FDA approved therapy, either in the adjuvant setting or for metastatic disease, with an impact on survival. Two subjects have been accrued into Phase IA as of 2-4-2021. References: (1)King DM, et al. J Clin Oncol 22:4463-4473, 2004. (2)Albertini MR, et al. Can Imm Imm 67(10):1647-1658, 2018. (3)Yang RK, et al. J of Imm 189:2656-2664, 2012. (4)Morris ZS et al. Can Res 76:3929-3941, 2016. Clinical trial information: NCT03958383.
Examination of the Igls Criteria for Defining Functional Outcomes of β-cell Replacement Therapy: IPITA Symposium Report
Authors: Landstra Cyril P , Andres Axel , Chetboun Mikael , Conte Caterina , Kelly Yvonne , Berney Thierry , de Koning Eelco J P , Piemonti Lorenzo , Stock Peter G , Pattou François , Vantyghem Marie-Christine , Bellin Melena D , Rickels Michael R 
Published: June 2021

Abstract

Context
The Igls criteria were developed to provide a consensus definition for outcomes of β-cell replacement therapy in the treatment of diabetes during a January 2017 workshop sponsored by the International Pancreas & Islet Transplant Association (IPITA) and the European Pancreas & Islet Transplant Association. In July 2019, a symposium at the 17th IPITA World Congress was held to examine the Igls criteria after 2 years in clinical practice, including validation against continuous glucose monitoring (CGM)-derived glucose targets, and to propose future refinements that would allow for comparison of outcomes with artificial pancreas system approaches.

Evidence acquisition
Utilization of the criteria in various clinical and research settings was illustrated by population as well as individual outcome data of 4 islet and/or pancreas transplant centers. Validation against CGM metrics was conducted in 55 islet transplant recipients followed-up to 10 years from a fifth center.

Evidence synthesis
The Igls criteria provided meaningful clinical assessment on an individual patient and treatment group level, allowing for comparison both within and between different β-cell replacement modalities. Important limitations include the need to account for changes in insulin requirements and C-peptide levels relative to baseline. In islet transplant recipients, CGM glucose time in range improved with each category of increasing β-cell graft function.

Conclusions
Future Igls 2.0 criteria should consider absolute rather than relative levels of insulin use and C-peptide as qualifiers with treatment success based on glucose assessment using CGM metrics on par with assessment of glycated hemoglobin and severe hypoglycemia events.
Who Counts Where? COVID-19 Surveillance in Federal Countries
Authors: Rocco Philip , Rich Jessica A. J. , Klasa Katarzyna , Dubin Kenneth A. , Béland Daniel 
Published: June 2021

Abstract
Context: While the World Health Organization (WHO) has established guidance on COVID-19 surveillance, little is known about implementation of these guidelines in federations, which fragment authority across multiple levels of government. This study examines how subnational governments in federal democracies collect and report data on COVID-19 cases and mortality associated with COVID-19.
Methods: We collected data from subnational government websites in 15 federal democracies to construct indices of COVID-19 data quality. Using bivariate and multivariate regression, we analyzed the relationship between these indices and indicators of state capacity, the decentralization of resources and authority, and the quality of democratic institutions. We supplement these quantitative analyses with qualitative case studies of subnational COVID-19 data in Brazil, Spain, and the United States.
Findings: Subnational governments in federations vary in their collection of data on COVID-19 mortality, testing, hospitalization, and demographics. There are statistically significant associations (p &lt; 0.05) between subnational data quality and key indicators of public health system capacity, fiscal decentralization, and the quality of democratic institutions. Case studies illustrate the importance of both governmental and civil-society institutions that foster accountability.
Conclusions: The quality of subnational COVID-19 surveillance data in federations depends in part on public health system capacity, fiscal decentralization, and the quality of democracy.
The early life of king penguins: ontogeny of dive capacity and foraging behaviour in an expert diver
Authors: Enstipp Manfred R. , Bost Charles-André , Le Bohec Céline , Chatelain Nicolas , Weimerskirch Henri , Handrich Yves 
Published: June 2021

ABSTRACT
The period of emancipation in seabirds, when juveniles change from a terrestrial existence to a life at sea, is associated with many challenges. Apart from finding favourable foraging sites, they have to develop effective prey search patterns and physiological capacities that enable them to capture sufficient prey to meet their energetic needs. Animals that dive to forage, such as king penguins (Aptenodytes patagonicus), need to acquire an adequate breath-hold capacity, allowing them to locate and capture prey at depth. To investigate the ontogeny of their dive capacity and foraging performance, we implanted juvenile king penguins before their first departure to sea and also adult breeders with a data-logger recording pressure and temperature. We found that juvenile king penguins possess a remarkable dive capacity when leaving their natal colony, enabling them to conduct dives in excess of 100 m within their first week at sea. Despite this, juvenile dive/foraging performance, investigated in relation to dive depth, remained below the adult level throughout their first year at sea, probably reflecting physiological limitations as a result of incomplete maturation. A significantly shallower foraging depth of juveniles, particularly during their first 5 months at sea, could also indicate differences in foraging strategy and targeted prey. The initially greater wiggle rate suggests that juveniles fed opportunistically and also targeted different prey from adults and/or that many of the wiggles of juveniles reflect unsuccessful prey-capture attempts, indicating a lower foraging proficiency. After 5 months, this difference disappeared, suggesting sufficient physical maturation and improvement of juvenile foraging skills.
Treatment Strategies and Prognosis of Patients With Synchronous or Metachronous Colorectal Peritoneal Metastases: A Population-Based Study
Authors: Bakkers C. , Lurvink R. J. , Rijken A. , Nienhuijs S. W. , Kok N. F. , Creemers G. J. , Verhoef C. , Lemmens V. E. , van Erning F. N. , De Hingh I. H. 
Published: June 2021

Abstract
Background
This study aimed to compare treatment strategies and survival of patients with synchronous colorectal peritoneal metastases (CPM) and patients with metachronous CPM in a nationwide cohort.

Methods
All patients from the Netherlands Cancer Registry with synchronous or metachronous CPM whose primary colorectal cancer (CRC) was diagnosed between 1 January and 30 June 2015 were included in the study. Treatments were categorized as (A) cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [CRS-HIPEC]; (B) palliative treatment; or (C) best supportive care. Overall survival (OS) for all the patients and disease-free survival (DFS) for those who underwent CRS-HIPEC were compared between the two groups.

Results
Of 7233 patients, 743 had a diagnosis of CPM, including 409 patients with synchronous CPM and 334 patients with metachronous CPM. The median OS was 8.1 months for the patients with synchronous CPM versus 12 months for the patients with metachronous CPM (p = 0.003). After multivariable correction, OS no longer differed between the patients with synchronous CPM and those with metachronous CPM (HR 1.03 [0.83–1.27]). The patients with metachronous CPM more often underwent CRS-HIPEC than the patients with synchronous CPM (16 % vs 8 %; p = 0.001). The two groups did not differ statistically in terms of DFS and OS (median DFS, 21.5 vs 14.1 months, respectively; p = 0.094; median OS, 37.8 vs. 35.8 months, respectively; p = 0.553).

Conclusion
This population-based study showed that survival for the patients with synchronous CPM and patients with metachronous CPM did not significantly differ. This suggests that a similar prognosis may be expected for patients selected for treatment regardless of the onset of CPM.
Characterization of vacuum and deep ultraviolet pulses via two-photon autocorrelation signals
Authors: Walker S. , Reiff R. , Jaron-Becker A. , Becker A. 
Published: June 2021

Characterization of ultrashort vacuum and deep ultraviolet pulses is important in view of applications of those pulses for spectroscopic and dynamical imaging of atoms, molecules, and materials. We present an extension of the autocorrelation technique, applied for measurement of the pulse duration via a single Gaussian function. Analytic solutions for two-photon ionization of atoms by Gaussian pulses are used along with an expansion of the pulse to be characterized using multiple Gaussians at multi-color central frequencies. This approach allows one to use two-photon autocorrelation signals to characterize isolated ultrashort pulses and pulse trains, i.e., the time-dependent amplitude and phase variation of the electric field. The potential of the method is demonstrated using vacuum and deep ultraviolet pulses and pulse trains obtained from numerical simulations of macroscopic high harmonic spectra.
Epidemiology, treatment, and survival in small cell lung cancer in Spain: Data from the Thoracic Tumor Registry
Authors: Franco Fernando , Carcereny Enric , Guirado Maria , Ortega Ana L. , López-Castro Rafael , Rodríguez-Abreu Delvys , García-Campelo Rosario , del Barco Edel , Juan Oscar , Aparisi Francisco , González-Larriba Jose L. , Domine Manuel , Trigo Jose M. , Cobo Manuel , Cerezo Sara , Calzas Julia , Massutí Bartomeu , Bosch-Barrera Joaquim , García Coves Paola , Domènech Marta , Provencio Mariano 
Published: June 2021

Background
Small-cell lung cancer (SCLC) is an aggressive disease with high metastatic potential and poor prognosis. Due to its low prevalence, epidemiological and clinical information of SCLC patients retrieved from lung cancer registries is scarce.

Patients and methods
This was an observational multicenter study that enrolled patients with lung cancer and thoracic tumors, recruited from August 2016 to January 2020 at 50 Spanish hospitals. Demographic and clinical data, treatment patterns and survival of SCLC patients included in the Thoracic Tumor Registry (TTR) were analyzed.

Results
With a total of 956 cases, the age of 64.7 ± 9.1 years, 78.6% were men, 60.6% smokers, and ECOG PS 0, 1 or ≥ 2 in 23.1%, 53.0% and 23.8% of cases, respectively. Twenty percent of patients had brain metastases at the diagnosis. First-line chemotherapy (CT), mainly carboplatin or cisplatin plus etoposide was administered to >90% of patients. In total, 36.0% and 13.8% of patients received a second and third line of CT, respectively. Median overall survival was 9.5 months (95% CI 8.8–10.2 months), with an estimated rate of 70.3% (95% CI 67.2–73.4%), 38.9% (95% CI 35.4–42.4%), and 14.8% (95% CI 11.8–17.8%) at 6, 12 and 24 months respectively. Median progression-free survival was 6.3 months. Higher mortality and progression rates were significantly associated with male sex, older age, smoking habit, and ECOG PS 1–2. Long-term survival (> 2 years) was confirmed in 6.6% of patients, showing a positive correlation with better ECOG PS, poor smoking and absence of certain metastases at diagnosis.

Conclusion
This study provides an updated overview of the clinical situation and treatment landscape of ES-SCLC in Spain. Our results might assist oncologists to improve current clinical practice towards a better prognosis for these patients.
Raman spectroscopy accurately differentiates mucosal healing from non-healing and biochemical changes following biological therapy in inflammatory bowel disease
Authors: Smith Samuel C. L. , Banbury Carl , Zardo Davide , Cannatelli Rosanna , Nardone Olga M. , Shivaji Uday N. , Ghosh Subrata , Oppenheimer Pola Goldberg , Iacucci Marietta 
Published: June 2021

Background
Mucosal healing (MH) is a key treatment target in the management of inflammatory bowel disease (IBD) and is defined in endoscopic terms by the newly published PICaSSO score. Raman Spectroscopy (RS) is based on the scattering of inelastic light giving spectra that are highly specific for individual molecules. We aimed to establish spectral changes before and after treatment and whether Raman Spectroscopy is able to accurately differentiate between inflammation and MH.

Methods
Biopsies were taken for ex vivo RS analysis alongside biopsies for histological analysis from IBD patients undergoing optical diagnosis endoscopic assessment. We compared pre- vs. post-biological treatment in IBD patients and healthy controls and active vs. MH in UC and CD. For spectral analysis, we used supervised self-organising maps for separation and classification.

Results
A total of 23 patients (14 IBD, 9 HC) were recruited for comparison of pre- vs. post-biologic treatment and 74 IBD patients were included for the assessment of MH in IBD, giving 9700 Raman Spectra. Spectral differences were seen between pre- and post-treatment which were observed comparing MH vs. active inflammation. Reductions in intensity at 1003cm-1 and 1252cm-1 when a reduction in inflammation was seen post-treatment and when MH was present. MH was associated with an increase in intensity at 1304cm-1. The trained neural network differentiated MH from active inflammation with a sensitivity, specificity, PPV, NPV and accuracy in UC of 96.29% (sd 0.94), 95.03% (sd 1.52), 94.89% (sd 1.59), 96.33 (sd 0.97) and 95.65 (sd 0.99) and 96.19% (sd 1.46), 88% (sd 4.20), 86.60% (sd 5.39), 96.55% (sd 1.32) and 91.6% (sd 2.75) in CD respectively.

Conclusion
We demonstrated RS can demonstrate biochemical changes following treatment of IBD and accurately differentiates MH from active inflammation in IBD and might be a future tool to personalise therapeutic management in IBD.
PROJECT FINANCING HOUSING CONSTRUCTION IN RUSSIA: RESULTS AND PROSPECTS
Authors: Glotova N. I. 
Published: June 2021

Housing construction is one of the main directions of the construction industry, while being a powerful driver of investment and consumer demand. It has a priority social significance and makes a significant contribution to the development of the economy.
Currently, in Russia, an increase in the volume of housing construction and the formation of an affordable housing market through the development of mortgage lending is one of the priority tasks of socio-economic development. Over the past three years, Russia has maintained a stable positive dynamics of housing commissioning. According to preliminary estimates, the targets set by the national project have been exceeded.
The article discusses the mechanism of transition of housing construction to project financing. The dynamics of opening escrow accounts in the context of Russian regions is analyzed. The assessment of the implementation of the preferential mortgage program in housing construction was carried out. The necessity of further improvement of the housing lending mechanism in modern conditions with the use of state support instruments is argued.
Tip-in Endoscopic Mucosal Resection for 15- to 25-mm Colorectal Adenomas: A Single-Center, Randomized Controlled Trial (STAR Trial)
Authors: Imai Kenichiro , Hotta Kinichi , Ito Sayo , Yamaguchi Yuichiro , Kishida Yoshihiro , Yabuuchi Yohei , Yoshida Masao , Kawata Noboru , Tanaka Masaki , Kakushima Naomi , Takizawa Kohei , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Mori Keita , Oishi Takuma , Ono Hiroyuki 
Published: June 2021

INTRODUCTION:
One-piece endoscopic mucosal resection (EMR) for lesions >15 mm is still unsatisfactory, and attempted 1-piece EMR for lesions >25 mm can increase perforation risk. Therefore, modifications to ensure 1-piece EMR of 15- to 25-mm lesions would be beneficial. The aim of this study was to investigate whether Tip-in EMR, which anchors the snare tip within the submucosal layer, increases en bloc resection for 15- to 25-mm colorectal lesions compared with EMR.

METHODS:
In this prospective randomized controlled trial, patients with nonpolypoid colorectal neoplasms of 15–25 mm in size were recruited and randomly assigned in a 1:1 ratio to undergo Tip-in EMR or standard EMR, stratified by age, sex, tumor size category, and tumor location. The primary endpoint was the odds ratio of en bloc resection adjusted by location and size category. Adverse events and procedure time were also evaluated.

RESULTS:
We analyzed 41 lesions in the Tip-in EMR group and 41 lesions in the EMR group. En bloc resection was achieved in 37 (90.2%) patients undergoing Tip-in EMR and 30 (73.1%) who had EMR. The adjusted odds ratio of en bloc resection in Tip-in EMR vs EMR was 3.46 (95% confidence interval: 1.06–13.6, P = 0.040). The Tip-in EMR and EMR groups did not differ significantly in adverse event rates (0% vs 4.8%) or median procedure times (7 vs 5 minutes).

DISCUSSION:
In this single-center randomized controlled trial, we found that Tip-in EMR significantly improved the en bloc resection rate for nonpolypoid lesions 15–25 mm in size, with no increase in adverse events or procedure time.
Accompagner les étudiants bacheliers bioingénieurs dans le développement de leurs compétences transversales
Authors: Descamps Charlotte , Gaspard François , Delmelle Pierre , Jacquemart Anne-Laure , Lecoq Julie 
Published: June 2021

Cet article propose de décrire la conception, le déroulé et l’évaluation de quatre modules de formation aux compétences transversales instaurés dans le cadre d’une réforme du programme de bachelier dans la Faculté des bioingénieurs de l’UCLouvain en réponse à deux enjeux facultaires : 1) intégrer les disciplines dans un contexte plus appliqué et 2) développer les compétences transversales des futurs bioingénieurs. Le scénario des modules prenait pour point d’ancrage la connaissance de soi et la conscience des différences interpersonnelles et visait un développement progressif des compétences de collaboration, d’organisation et de communication, en articulation directe à la réalisation d’un projet. Quarante-quatre équipes d’étudiants ont pris part au dispositif. Celui-ci a fait l’objet d’une évaluation quantitative (enquête) et qualitative (focus group). Les résultats intègrent des mesures de l’efficacité du groupe et des émotions vécues.