bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-center experience of PD1 inhibition in metastatic uveal melanoma.
Authors: Xu Tan , Song Jung Min , McNamara Michael J. , Gastman Brian , Singh Arun D , Funchain Pauline 
Published: November 2019

87 Background: Metastatic uveal melanoma (MUM) is a rare histology with poor prognosis. Therapies used in cutaneous melanoma with success have limited to no efficacy in uveal melanoma. Limited data exists regarding the efficacy of PD-1 inhibition in this disease. Methods: Patients carrying a diagnosis of MUM that had been treated with any PD1 inhibitor at the Cleveland Clinic were analyzed. Median overall survival from the diagnosis of metastatic disease and from the start of PD-1 inhibition were calculated. RECIST 1.1 criteria were used to assess response to therapy. Results: 10 patients with MUM have been treated with a PD1 inhibitor. Mean age at initiation of PD1 inhibition was 74. Five (50%) were female. Median time from initial diagnosis to metastatic disease was 67 months (range, 5-204). All 6 patients with a genetic profiling result available were classified as poor risk either by cytogenetics or gene expression profiling. Median overall survival from diagnosis of metastatic disease was 24 months (range, 9-46). Six patients had also been treated with ipilimumab, 4 had prior treatment, 1 had PD-1 prior to ipilimumab, and one had concurrent treatment with combination ipilimumab/nivolumab. Adjunct local radiation occurred in 6 patients: 5 of the liver (4 embolization, 1 SBRT), one of osseous metastases. Median time on PD1 treatment was 2 months (range, 1-6). Two patients had SD, 6 PD, 3 have not yet been reevaluated. Median survival from initiation of PD1 inhibition was 9 months (range, 7-12). Adverse events were as expected from published experiences with PD-1 inhibition. All patients with median survival from initial diagnosis of metastatic disease over one year received both PD-1 and CTLA-4 inhibition as well as radiation. Conclusions: In this single center experience, no patients had tumor response to PD-1 inhibition. Combination therapies may be worth exploring in the treatment of MUM.
Tremelimumab: A monoclonal antibody against CTLA-4—In combination with radiofrequency ablation (RFA) in patients with biliary tract carcinoma (BTC).
Authors: Duffy Austin G. , Pratt Drew , Kleiner David E , Mabry Donna , Fioravanti Suzanne , Walker Melissa , Figg William Douglas , Steinberg Seth M. , Anderson Victoria , Levy Elliot , Krishnasamy Venkatesh , Wood Bradford J. , Greten Tim F. 
Published: November 2019

88 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. Radiofrequency ablation (RFA) has been shown to induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment. Methods: Patients with refractory BTC were enrolled in a study of monthly Tremelimumab (10mg/kg, 6 doses) combined with RFA (to one lesion) performed on week 6. Tumor biopsies were performed at time of RFA with regular PBMC collection for intensive immunemontoring. Results: 17 pts enrolled. Characteristics: M:F 8:9; Median age 57(range 36-67); BTC subtype - intrahepatic/exrahepatic: 12/5. 13/17 had metastatic disease. All pts were chemorefractory with 12/17 having received at least 2 regimens. While on study, 6 pts had early PD within 6 weeks; 11 were able to undergo RFA. No DLT encountered. Most common toxicity was pruritus. There were no objective responses. Of evaluable pts N = 6 (55%) had stable disease as a best response. Conclusions: Tremelimumab in combination with subtotal RFA in patients with advanced BTC is safe and feasible. No objective responses have so far been seen in this predominantly primary intrahepatic BTC population. Full efficacy and immune monitoring data will be presented. Clinical trial information: NCT01853618.
Single-center experience with nivolumab in pretreated patients with non-small cell lung cancer (NSCLC).
Authors: Rapoport Bernardo Leon , Smit Teresa , van Eeden Ronwyn 
Published: November 2019

90 Background: Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity in NSCLC patients. Methods: A retrospective review of data from 20 patient records were used to describe the response of patients with NSCLC receiving treatment with Nivolumab after failing chemotherapy. Two patients were too early to evaluate. Results: A total of 18 patients (pts) (10 males and 8 females) were included in the analysis. The median age was 66 years (range 46-85). Adenocarcinoma was documented in 15 pts and squamous cell carcinoma in 3 pts. A Ros-1 positive mutation was documented in 1 pt, 3 EGFR positive mutations were recorded and no pts tested positive for ALK. All pts failed frontline treatment: 14 pts failed platinum based chemotherapy and 4 pts failed TKI-inhibitors (3 on erlotinib and 1 on crizotinib). Pts received a median of 4 cycles of nivolumab (range 1-16). The performance status ranged from 0 to 2 (median 1). The median number of metastatic sites was 3 (range 1-5). Four partial responses were documented (23.5% 95% CI 3-43%), with response durations of 232, 113, 63 and 30 days. Disease stabilization was documented in 7 pts. There were no complete responses so far, and 6 pts showed progressive disease. Two pts were too early to evaluate and one pt was non-evaluable (died due to progresive diease before treatment initiation). No responses were seen amongst the pts who received prior TKI treatment. Documented toxicities included pulmonitis in 2 pts, chest infections in 4 pts (one pt with documented tuberculosis), fatigue in 4 pts and skin rash, diarrhoea and headaches in 1 pt, respectively. The median survival was 124 days (13-289). Conclusions: In this retrospective study nivolumab was an active and well tolerated treatment in pts with pretreated NSCLC.
Combining PD-1 blockade with T-cell redirecting bispecific antibodies for solid cancer therapy.
Authors: Chang Chien-Hsing , Wang Yang , Rossi Diane L , Li Rongxiu , Rossi Edmund A. , Cardillo Thomas M. , Goldenberg David M. 
Published: November 2019

98 Background: Bispecific antibodies (bsAbs) for redirecting T cells to cancers have shown promise in both preclinical and clinical studies. However, clinical results have been disappointing in solid cancers. We have applied the DOCK-AND-LOCK method to generate a novel class of trivalent bsAbs, each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. Herein we report the characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2- and CEACAM5-expressing cancer cells, respectively. Methods: Human breast and colonic cancer cell lines were grown in monolayer cultures or as 3D spheroids for in vitro evaluation. NOD/SCID mice carrying xenografts of MDA-MB-231 (a TNBC line constitutively expressing Trop-2 and PD-L1) were used for in vivo studies. A human PD-1 antagonistic murine hybridoma antibody was subsequently converted to its chimeric form (IMMU-cPD-1). Human PBMCs, or T cells isolated from buffy coats by negative selection, were used as effector cells in cytotoxicity assays. The effect of IMMU-cPD-1 on cancer cells pretreated with IFN-γ to induce the expression of PD-L1 was compared with those not pretreated. Results: (E1)-3s and (14)-3s, in the presence of human T cells, killed target cells grown as monolayers at low picomolar concentrations, with similar potency observed for drug-resistant cells. The antitumor efficacy was demonstrated for (E1)-3s plus human PBMCs in NOD/SCID mice bearing MDA-MB-231, and for human PBMCs combined with (E1)-3s or (14)-3s in 3D spheroids generated from target cell lines to mimic the in vivo behavior and microenvironment of these tumors. Moreover, with the addition of IMMU-cPD-1, the benefit of PD-1 blockade was indicated by increased cell death in 3D spheroids and longer survival of MDA-MB-231-bearing mice. Conclusions: These results highlight the potency of (E1)-3s and (14)-3s as T-cell redirecting bsAbs, emphasize the potential of combining such bsAbs with immune checkpoint inhibitors to improve the therapeutic activity in the immunotherapy of solid cancers, and provide a basis for using 3D spheroids as an alternative to in vivo models for evaluating T-cell functions.
Imagining Otherly
Authors: Ridley LaVelle 
Published: November 2019

Abstract
In this article the author focuses on Mya Taylor's singing performance as Alexandra in the 2015 comedy-drama film Tangerine as a performative index of black trans women's futures. Contextualizing her performance within the larger, dangerous world for most black trans sex workers that the film portrays largely without critique, the author argues that this scene offers Alexandra, and black trans viewers of the film, a brief reprieve from the anxieties of social and state oppression and allows her (and us) to breathe, and within that breath to imagine toward radical futures that resist the binary of resistance and compliance, to imagine otherly. The author draws on black trans studies, black feminist theory, and black cultural and media studies to articulate how this film as a unique and crucial moment of black trans cultural production also offers us a key moment in theorizing black trans epistemology.
From Duration to Self-Identification?
Authors: Draz Marie 
Published: November 2019

AbstractThis article examines the temporal politics of the 2017 California Gender Recognition Act (CGRA). The author first offers a brief history of the dominant temporal requirements for “gender recognition” in prior legislation around sex/gender markers on identity documents in the United States and United Kingdom, focusing on how this legislation places temporal boundaries around legitimate gender identity. Then, turning directly to the CGRA, the author asks to what extent the act's emphasis on self-identification revises or intervenes in these prior conceptualizations of time and identity by the state administration of sex/gender systems. The article closes with an exploration of the temporality of identity documentation itself, speculating about how this legislation might be placed more directly into conversation with the role of time in colonial and racial state building.
The role of noncoding mutations in blood cancers
Authors: Rahman Sunniyat , Mansour Marc R. 
Published: November 2019

ABSTRACT
The search for oncogenic mutations in haematological malignancies has largely focused on coding sequence variants. These variants have been critical in understanding these complex cancers in greater detail, ultimately leading to better disease monitoring, subtyping and prognostication. In contrast, the search for oncogenic variants in the noncoding genome has proven to be challenging given the vastness of the search space, the intrinsic difficulty in assessing the impact of variants that do not code for functional proteins, and our still primitive understanding of the function harboured by large parts of the noncoding genome. Recent studies have broken ground on this quest, identifying somatically acquired and recurrent mutations in the noncoding genome that activate the expression of proto-oncogenes. In this Review, we explore some of the best-characterised examples of noncoding mutations in haematological malignancies, and highlight how a significant majority of these variants impinge on gene regulation through the formation of aberrant enhancers and promoters. We delve into the challenges faced by those that embark on a search for noncoding driver mutations, and provide a framework distilled from studies that have successfully identified such variants to overcome some of the most salient hurdles. Finally, we discuss the current therapeutic strategies being explored to target the oncogenic mechanism supported by recurrent noncoding variants. We postulate that the continued discovery and functional characterisation of somatic variants in the noncoding genome will not only advance our understanding of haematological malignancies, but offer novel therapeutic avenues and provide important insights into transcriptional regulation on a broader scale.
Earmarking Donations to Charity: Cross-cultural Evidence on Its Appeal to Donors Across 25 Countries
Authors: Fuchs Christoph , de Jong Martijn G. , Schreier Martin 
Published: November 2019

Charity organizations differ in their practice of offering donors the option to earmark their contribution: allowing donors to select the project in which their money should be invested. This paper presents two studies that provide the first empirical evidence on the appeal of such earmarking. The empirical basis of Study 1 is a unique data set consisting of 7,383 potential donors from 25 countries who participated in a randomized survey experiment. First, we find that the willingness to donate is significantly higher when earmarking is allowed. Second, we find that the effect of earmarking substantially differs in magnitude across countries. Third, we identify two cross-cultural interactions. Specifically, earmarking is less effective in countries that score lower on autonomy relative to embeddedness and in those scoring lower on egalitarianism relative to hierarchy. Fourth, we find that the earmarking effect is driven mainly by the activation of more donors and not by increases in the amounts that donors contribute. Study 2 is a follow-up experiment that replicates the basic earmarking effect, addresses limitations of our cross-cultural study, and sheds some preliminary light on the effect’s underlying process. We find that earmarking options increase potential donors’ perceptions of being able to make specific impact and also that this sense of agency helps us to understand an individual’s increased willingness to donate. This paper was accepted by Eric Anderson, marketing.
Longing and belonging through migration: Otherness and empathy in theatre and philosophy
Authors: Corrêa Graça P. 
Published: November 2019

Abstract
This article examines how theatre and philosophy may critically contribute to discussing empathy towards otherness in the context of the ongoing massive surge of migration across the globe. Drawing on concepts from philosophical works by Baruch Spinoza, Henri Bergson and Jacques Derrida, it investigates how different dramaturgical techniques and aesthetics – namely in Euripedes' Children of Heracles (c.430 BCE), Roland Schimmelpfennig's The Golden Dragon (2009) and Nikos Kazantzakis and Graça P. Corrêa's Christ Recrucified (1954/2018) – address ethical-affective percepts such as empathy and hospitality in a theatre dealing with migration experiences.
TRANSFORMASI NITROGEN DI LAUT
Authors: Meirinawati Hanny 
Published: November 2019

NITROGEN TRANSFORMATION IN MARINE ENVIRONMENT. Nitrogen transformations are undertaken by marine organisms as part of their metabolisms, either to obtain nitrogen to synthesize structural components or to gain energy for their growth. Nitrogen can stimulate primer productivity in an aquatic ecosystem. Increasing human activities can cause the increase of the number of nitrogen in the ocean. The increased input of nitrogen which is often accompanied by oxygen limitation has a strong negative effect on benthic metabolism and nitrogen mineralization. The ocean’s nitrogen cycle is driven by complex microbial transformations, including nitrogen fixation, assimilation, nitrification, anammox (anaerobic ammonium oxidation) and denitrification.
Allah'ın Kudreti'nin İnsan Fiillerine Taalluk Alanı ve İmkânı (Kötülük Problemi Çerçevesinde Bir İnceleme)
Authors: CAN Seyithan 
Published: November 2019

Tanrı inancına sahip teolojilerde, O’na
atfedilen kudretin yetkin olarak nitelendirilmesi, aynı zamanda bu kudretin
etki ettiği alanın sınırsız olduğuna yönelik bir düşüncenin oluşmasına
sebebiyet vermiştir. Tanrı’nın
mutlaklığı açısından ele alınan bu düşünce, ateistlerin en temel argümanı olan
kötülük problemini, Tanrı’nın kudret sıfatını, işlevselliği açısından
teistlerin önüne müşkil bir mesele haline getirmiştir. Çünkü Tanrı kötülüğü
önlemek istiyor da, gücü mü yetmiyor? gibi bir soruya Tanrı inancına sahip
bütün insanlar; “Tanrı, her yönüyle mutlak sıfatlara sahiptir. Dolayısıyla O,
her şeye gücü yetendir” cevabını vereceklerdir. O halde neden kötülüğe müdahale
etmiyor? sorusu, hem inanan hem de inanmayan herkes için temel bir problem
haline gelmektedir.

Bu çalışma günümüzde de hala güncelliğini koruyan kötülük problemi
çerçevesinde, Allah’ın insan fiillerine müdahalesi tartışmalarına ilk dönem
(Mutekaddimûn) Mu’tezile, Eş’arî ve
Mâturîdî kelamcılarının görüşleri kapsamında cevap aramaktadır. Mutlak
kudretin âleme taalluku kötülük problemi çerçevesinde ele alındığında,
Mu’tezile’nin aslah teorisi kapsamında mutlak iyi Tanrı perspektifinde hareket
ettiğini görüyoruz. Bu noktada Eş’arîler’in, mutlak iyi Tanrı tasavvuru
geliştirmedikleri ve Tanrı’nın âlemle ilişkisini sadece onun mutlak kudreti
üzerinden şekillendirdikleri görülmektedir. Mâturîdîler, her ne kadar hikmetli
ve bağımlı müdahale anlayışı çerçevesinde Allah’ın kudretini insanın azm ve
isteğine göre sınırlandırsalar da mutlak kudretin her şeyi yaratması noktasında
Eş’âriler’e daha yakın bir çizgide olduklarını söyleyebiliriz.
Pull-Back of Metric Currents and Homological Boundedness of BLD-Elliptic Spaces
Authors: Pankka Pekka , Soultanis Elefterios 
Published: November 2019

Abstract
Using the duality of metric currents and polylipschitz forms, we show that a BLD-mapping f : X → Y between oriented cohomology manifolds X and Y induces a pull-back operator f
* : M
k,loc(Y) → M
k,loc(X) between the spaces of metric k-currents of locally finite mass. For proper maps, the pull-back is a right-inverse (up to multiplicity) of the push-forward f
* : M
k,loc(X) → M
k,loc(Y).
As an application we obtain a non-smooth version of the cohomological boundedness theorem of Bonk and Heinonen for locally Lipschitz contractible cohomology n-manifolds X admitting a BLD-mapping ℝ
n
→ X.
Terpenoids and phytosteroids isolated from Commelina benghalensis Linn. with antioxidant activity
Authors: Khatun Amina , Rahman Mahmudur , Rahman Mohammad Sharifur , Hossain Md. Khalid , Rashid Mohammad Abdur 
Published: November 2019

Abstract

Background

Commelina benghalensis Linn. (Family: Commelinaceae) is a common weed available in Bangladesh with several uses in traditional medicine. However, the chemical profile of this medicinal plant is scarce in relation to its medicinal uses. The aerial parts of this plant have been investigated for the isolation of secondary metabolites and evaluation of the biological activities.

Methods
Major phytochemical groups were analyzed using chromogenic reagents, whereas n-hexane soluble fractionates of the methanol extract were subjected to 1H nuclear magnetic resonance (NMR) spectroscopic analysis. The antioxidant property of the obtained compounds was evaluated using 1,1-diphenyl-2-picryl-hydrazyl (DPPH).

Results
Dammara-12-en-3-one (CB-1), stigmasterol (CB-2) and 3 (2,3,4,5,6-pentahydroxy)-cinnamoyl dammara-12-ene (CB-3) were isolated from the n-hexane fractionate of methanol extract of C. benghalensis. In the study of DPPH radical scavenging activity, IC50 values were predicted to be 790.18, 4186.94 and 2001.16 μg/mL for CB-1, CB-2 and CB-3, respectively, whereas standard ascorbic acid showed IC50 at 1.26 μg/mL.

Conclusions
Two new dammarane-type triterpene (CB-1 and CB-3) and one phytosterol (CB-2) were identified in C. benghalensis with mild antioxidant property.
Li vs. Zn substitution in Li17Si4 – Li17–

ε

–

δ
Zn
ε
Si4 connecting the structures of Li21Si5 and Li17Si4
Authors: Baran Volodymyr , Fässler Thomas F. 
Published: November 2019

Abstract
Binary lithium silicides play a crucial role in high energy density anode materials for rechargeable batteries. During charging processes of Si anodes Li15Si4 is formed as a metastable phase which has been stabilized through Li by Mg, Zn and Al substitution. Here we investigate Li by Zn substitution in the lithium-richest phase Li17Si4 and report on the particular site preference of Zn atoms since Zn is substituting Li atoms only on one out of 13 possible lithium sites. This site preference shows an interesting relation to the closely related phase Li21Si5 and thus Li17−

ε

−

δ
Zn
ε
Si4 with ε = 0.025(1) and δ = 0.033(1) can be considered as the missing link between the structures of Li21Si5 (= Li4.20Si) and Li17Si4 (= Li4.25Si).
Cs2Zn(CN)4: a first example of a non-cyano spinel of composition A2M(CN)4 with A=alkali metal and M=group 12 metal
Authors: Werker Melanie , Ruschewitz Uwe 
Published: November 2019

Abstract
The crystal structure of monoclinic Cs2Zn(CN)4 (C2/c, Z = 4) was solved and refined from high-resolution synchrotron powder diffraction data (ESRF: Swiss-Norwegian beamline). In contrast to all other known cyanides of composition A2M(CN)4 with A = alkali metal and M = group 12 metal, which crystallize in cubic or rhombohedrally distorted spinel variants and thus with A+ in an octahedral coordination, the Cs+ cation in Cs2Zn(CN)4 shows an eight-fold coordination by CN− anions of the [Zn(CN)4]2− tetrahedra. Upon heating, no phase transition is observed. Instead, a reversible melting at approx. T = 380°C occurs.
Increased risk of low bone mineral density in patients with non-alcoholic fatty liver disease: a cohort study
Authors: Shen Zhe , Cen Li , Chen Xufeng , Pan Jiaqi , Li Youming , Chen Weixing , Yu Chaohui 
Published: November 2019

Background
Non-alcoholic fatty liver disease (NAFLD) has been suggested to be a risk factor associated with low BMD (bone mineral density) in several cross-sectional studies. The present longitudinal cohort study aims to explore the effect of NAFLD and its severity on low BMD.

Methods
Between January 2013 and August 2018, individuals who participated in annual comprehensive health examinations were included. BMD was presented using dual-energy X-ray absorptiometry (DXA). These subjects were diagnosed with fatty liver by ultrasound detection.

Results
A total of 1720 subjects were included (1064 subjects with normal BMD and 656 subjects with low BMD) at baseline. Among the 1064 participants with normal BMD at baseline, 399 participants developed low BMD. The multivariable-adjusted hazard ratio for incident low BMD comparing the NAFLD group vs the non-NAFLD group was 2.24 (1.18, 2.81). Increased non-invasive fibrosis markers of NAFLD were positively associated with an increased incidence of low BMD in a graded manner. In addition, obese subjects and women with NAFLD at baseline are more likely to develop low BMD.

Conclusion
NAFLD and its severity were independently associated with an increased incidence of low BMD. Obesity and female gender are risk factors associated with low BMD. Our findings indicated NAFLD can be a significant contributor to low BMD pathogenesis, requiring further studies to elucidate the potential mechanisms.
COSTA RICA SIN FRONTERAS #13
Authors: Aragón-Vargas Luis Fernando 
Published: November 2019

En esta sección se publican los resúmenes en español de artículos que han sido publicados por investigadoras/es de universidades costarricenses en otras revistas en el mundo, con su debida referencia al trabajo original, y con una breve explicación de dónde se realizó la investigación. Los artículos originales han sido publicados en otros idiomas; las revistas tienen consejo editorial y manejan un proceso de revisión por pares. Los resúmenes corresponden a estudios relacionados con las ciencias del ejercicio y la salud, que se conforman a los criterios generales de la revista, esto es, se trata de “... estudios experimentales o que hagan recomendaciones concretas para solucionar problemas o preguntas relevantes (...) trabajos originales o de meta-análisis.” Solicitamos a las personas que han publicado este tipo de trabajos en otros idiomas que no los hagan saber, para incluir sus resúmenes en futuras entregas de esta sección.