bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P070: The safety and efficacy of Durvalumab and Paclitaxel combination in metastatic triple-negative breast cancer: An open-label phase I/II trial with 2-years follow-up
Authors: Ghebeh Hazem , Al-Sayed Adher , Suleman Kauser , Eiada Riham Eiada , Tulbah Asma , Al-Tweigeri Taher 
Published: January 2022

Abstract
Weekly paclitaxel is an excellent therapeutic choice for metastatic triple-negative breast cancer, a type of cancer that typically has short survival. There is evidence that TNBC is relatively more immunogenic; THEREFORE, we tested the safety and efficacy of weekly paclitaxel at 80 mg/m2/IV given in combination with Durvalumab, (an anti-PD-L1). During a period of 24 MONTHS, 14 patients received the combination OF six cycles of concurrent weekly paclitaxel given on days 1, 8, and 15/IV and Durvalumab given on days 1 and 15/IV of every 28 days' cycle. Upon completion of this combination, Durvalumab was given every 2 weeks until disease progression or unacceptable toxicity. The combination therapy had an excellent safety profile with no dose reduction, dose-limiting toxicity, OR death related to combination therapy. Adverse events (AEs) reported in 10 (71%) of patients, regardless of grade, while grade 3 or 4 AEs happening in 3 (21%) patients only. The most common AEs, were peripheral neuropathy and headache, which happened in 4 patients (29%) followed by fatigue and skin rash occurred in 3 patients (21%). Other less common AEs included: Anemia, leukopenia and/or neutropenia, diarrhea, alopecia, palpitation, and weight gain. The overall response rate for the combination was 36% (confirmed), with a median duration OF RESPONSE of 10 months. The median progression-free survival (PFS) and overall survival (OS) was 5.0 AND 20.7 months, respectively. In conclusion, WE ARE REPORTING an excellent safety profile for the weekly paclitaxel and Durvalumab combination. The data should be looked at with caution due to the small number of patients. Due to excellent safety profile, further trials involving additional, possibly synergistic, agents to the paclitaxel/Durvalumab combination are encouraged.
Citation Format: Hazem Ghebeh, Adher Al-Sayed, Kauser Suleman, Riham Eiada Eiada, Asma Tulbah, Taher Al-Tweigeri. The safety and efficacy of Durvalumab and Paclitaxel combination in metastatic triple-negative breast cancer: An open-label phase I/II trial with 2-years follow-up [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P070.
Abstract P073: Gut microbiota shift in melanoma patients undergoing immunotherapy is associated with clinical response
Authors: Macandog Angeli Dominique , Catozzi Carlotta , Cassano Ester , Gandini Sara , Ferrucci Pier Francesco , Cocorocchio Emilia , Manzo Teresa , Nezi Luigi 
Published: January 2022

Abstract
Background: The high resistance of melanoma to targeted therapy has made it a persistently lethal cancer type. Although the advent of immune checkpoint inhibition (ICI) therapy markedly improved outcome for melanoma in recent years, response remains heterogenous, with only 20-40% of patients achieving clinical response for anti-CTLA4 or anti-PD1 therapy. This variability in response has urged research towards host factors that drive response to immunotherapy, and studies have come out to show that the gut microbiota influences immunotherapy response. More importantly, mouse studies and more recent human clinical trials demonstrate that transplantation of responder (R) microbiota improves host immunity and alleviates tumor growth during immunotherapy. Although these findings confirm a close relationship between the gut microbiota and antitumor host immunity, FMT human clinical trials on melanoma patients report success in only 30-40% of patients, suggesting that current knowledge of underlying immunomodulatory mechanisms of the gut microbiota are still limited, and that analysis of data collected only before start of therapy is insufficient. Notably, there is a lack of published longitudinal studies that monitor gut microbiome changes during melanoma immunotherapy.
Methods: We performed longitudinal analysis of the gut microbiota in melanoma patients undergoing NEOAJUVANT immunotherapy, revealing distinct dynamics between R and non-responders (NR) over the course of treatment. Sequencing data were paralleled with a quantitative analysis of circulating inflammatory molecules, suggesting a dynamic interaction between the gut microbiota and immune system. Here, we will present key modulators of the immune cell compartment.
Conclusions: Overall, our results highlight the importance of longitudinal analysis to dissect the role of the gut microbiota on response to immunotherapy.
Citation Format: Angeli Dominique Macandog, Carlotta Catozzi, Ester Cassano, Sara Gandini, Pier Francesco Ferrucci, Emilia Cocorocchio, Teresa Manzo, Luigi Nezi. Gut microbiota shift in melanoma patients undergoing immunotherapy is associated with clinical response [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P073.
Abstract P077: Composition of CD4 T cell subsets and impact on tumor growth control across mouse syngeneic tumor models
Authors: Xu Chunxiao , Webb Lindsay , Yalavarthi Sireesha , Bourin Clotilde , Moisan Jacques 
Published: January 2022

Abstract
CD4 T cells include multiple sublineages orchestrating a broad range of effector activities during the initiation, promotion, and progression of carcinogenesis. Although regulatory T cells (Tregs) are well-characterized to promote tumor progression, the impact of effector CD4+ T cell subsets (Teff) in anti-tumor immunity is less well known. Further, the relative contribution of Teff and Treg cell subsets in different syngeneic tumor models has not been characterized. We observed that CD4 depletion had significantly different impact of tumor growth across different syngeneic tumor models: no effect on MC38 tumor growth; enhanced tumor growth in CT26.KSA tumor model; while almost complete tumor regression in the EMT-6 tumor model. We hypothesized that each tumor model has a vastly different composition in the CD4 T cell compartment. To test this, we characterized expression of activation and CD4 T cell differentiation markers as well as cytokine production from CD4 TILs in each of the syngeneic tumor models. We found that while effector CD4 TILs (FoxP3−CD4+) from MC38 and CT26.KSA tumors expressed high levels activation and differentiation markers, Teff from EMT-6 tumors expressed very low levels of T cell activation and differentiation markers, suggesting the Teff in EMT-6 tumors are largely dysfunctional. Ex vivo restimulation of tumor samples with anti-CD3/anti-CD28 promoted IFNγ production in CD4 TILs from MC38 and CT26.KSA tumor models, but not from EMT-6 tumor models, further supporting that Teff from MC38 and CT26.KSA tumors remain highly active, while CD4 TILs from EMT-6 tumors are dysfunctional. When looking at the Treg compartment, the frequency of Tregs in CT26.KSA tumors was reduced compared to MC38 and EMT-6 tumors. Further, Tregs in MC38 and EMT-6 tumors expressed very high levels of CD69, a marker of highly immunosuppressive Tregs, while Tregs in CT26.KSA tumors expressed lower levels of CD69, suggesting that these Tregs may be less immunosuppressive. In summary, the CD4 T cell compartment is vastly different across CT26.KSA, MC38 and EMT-6 syngeneic tumor models, resulting in very different impact of tumor growth control.
Citation Format: Chunxiao Xu, Lindsay Webb, Sireesha Yalavarthi, Clotilde Bourin, Jacques Moisan. Composition of CD4 T cell subsets and impact on tumor growth control across mouse syngeneic tumor models [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P077.
Abstract PR08: Context is everything: Microbiota-specific T follicular helper cells in colorectal cancer
Authors: Overacre-Delgoffe Abigail E. , Bumgarner Hannah J. , Cillo Anthony R. , Burr Ansen H. P. , Tometich Justin T. , Bhattacharjee Amrita , Bruno Tullia C. , Vignali Dario A. A. , Hand Timothy W. 
Published: January 2022

Abstract
Colorectal cancer (CRC) is the third most common and one of the deadliest cancers in the US, and the survival rate for advanced cases is poor. Immunotherapy, especially checkpoint blockade, has revolutionized the way cancer is treated and has resulted in longterm, durable responses for some epithelial cancers. Unfortunately, CRC remains largely unresponsive to current immunotherapies, with only ~6% of total patients responding to anti-PD1. Therefore, it is necessary to not only determine hurdles that are preventing checkpoint blockade response, but to also develop novel therapies to use in conjunction with current therapies. The microbiome has recently been associated with better anti-PD1 response in melanoma patients; however, the underlying mechanism by which select bacteria provide a benefit and whether this can be applied to other cancer types remains unclear. The majority of microbes live within the gut, and adherent bacteria can have direct interaction with the colonic epithelium, resulting in a bacteria-specific immune response. Therefore, we hypothesized that rational modification of the microbiome may support anti-tumor immunity through activation of microbiota-specific T cells. Using a carcinogen-induced mouse model of CRC, we found that addition of a single colonic-residing, adherent bacteria (Helicobacter hepaticus, Hhep) after tumors had formed led to a significant reduction in tumor burden and a 2-3 fold increase in overall survival. Interestingly, Hhep colonization led to the activation of Hhep-specific T follicular helper cells (TFHs) that supported formation of large, organized tertiary lymphoid structures (TLS) found adjacent to or within tumors themselves. The presence of TLS supported an increase in cytotoxic lymphocytes (T and NK cells) specifically within the tumor core. Somewhat strikingly, the anti-tumor response was dependent on CD4+ T cells but not CD8+ T cells. Using TFH KO mice, we found that Hhep-specific T cells were both necessary and sufficient to drive TLS maturation, anti-tumor immunity, and ultimately, longterm survival in CRC. Overall, these findings suggest that microbiome modulation and the subsequent microbiota-specific CD4+ T cell response may represent a new immunotherapeutic target for cancer subtypes that remain resistant to checkpoint blockade.
Citation Format: Abigail E. Overacre-Delgoffe, Hannah J. Bumgarner, Anthony R. Cillo, Ansen H. P. Burr, Justin T. Tometich, Amrita Bhattacharjee, Tullia C. Bruno, Dario A. A. Vignali, Timothy W. Hand. Context is everything: Microbiota-specific T follicular helper cells in colorectal cancer [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr PR08.
Garantias externas e fundamentos internos: dimensões da legitimidade em Max Weber
Authors: Sell Carlos Eduardo 
Published: January 2022

O artigo propõe uma reconstrução histórico-sistemática do conceito de legitimidade no âmbito do pensamento político e sociológico de Max Weber. Na primeira parte (histórica), contrapondo-se à tese de que haveria uma ruptura no pensamento de Weber, argumenta-se que a dimensão estrutural e a dimensão simbólica são variáveis que possuem o mesmo peso analítico na determinação teórica das formas de dominação. Na segunda parte (sistemática), após demonstrar o conteúdo prescritivo e normativo inerente ao conceito de legitimidade, ele será examinado ainda na sua dimensão macrossocial, enquanto “garantia de legitimidade”, e na sua dimensão microssocial, enquanto “fundamento da legitimidade”. Ao separar analiticamente cada um desses aspectos, Weber nos legou os alicerces de um conceito multidimensional de legitimidade que estabelece um elo intrínseco entre as estruturas políticas e seus fundamentos normativos.
Witnessing Women: Quo Vadis, Cinema?
Authors: Jelača Dijana 
Published: January 2022

Abstract
The essay explores how two women filmmakers, each deploying her unique vision through the perspective of a female protagonist, stage a transformative encounter with the act of bearing witness to genocide. The Diary of Diana B. (Dnevnik Diane Budisavljević, 2019, Croatia) directed by Dana Budisavljević, and Quo Vadis, Aida? (2020, Bosnia-Herzegovina), directed by Jasmila Žbanić, both compel us to bear witness to mass atrocities while avoiding the pitfalls of turning suffering into a spectacle, and by sidestepping the predictable cinematic conventions of redemption and closure, both formally and narratively. In my analysis of the films as anti-spectacles through the framework of Trinh T. Minh-ha’s ‘speaking nearby’, I argue for the concept of ‘women’s world cinema’, a kind of cinema that is made by women, speaks to women’s experiences, and/or addresses the spectator as female while also speaking nearby instead of about its subjects in ways that eschew conventional spectatorial alignments and co-optations of traumatic experience.
Export of Ice Sheet Meltwater from Upernavik Fjord, West Greenland
Authors: Muilwijk Morven , Straneo Fiamma , Slater Donald A. , Smedsrud Lars H. , Holte James , Wood Michael , Andresen Camilla S. , Harden Ben 
Published: January 2022

Abstract
Meltwater from Greenland is an important freshwater source for the North Atlantic Ocean, released into the ocean at the head of fjords in the form of runoff, submarine melt, and icebergs. The meltwater release gives rise to complex in-fjord transformations that result in its dilution through mixing with other water masses. The transformed waters, which contain the meltwater, are exported from the fjords as a new water mass Glacially Modified Water (GMW). Here we use summer hydrographic data collected from 2013 to 2019 in Upernavik, a major glacial fjord in northwest Greenland, to describe the water masses that flow into the fjord from the shelf and the exported GMWs. Using an optimum multi-parameter technique across multiple years we then show that GMW is composed of 57.8% ± 8.1% Atlantic Water (AW), 41.0% ± 8.3% Polar Water (PW), 1.0% ± 0.1% subglacial discharge, and 0.2% ± 0.2% submarine meltwater. We show that the GMW fractional composition cannot be described by buoyant plume theory alone since it includes lateral mixing within the upper layers of the fjord not accounted for by buoyant plume dynamics. Consistent with its composition, we find that changes in GMW properties reflect changes in the AW and PW source waters. Using the obtained dilution ratios, this study suggests that the exchange across the fjord mouth during summer is on the order of 50 mSv (1 Sv ≡ 106 m3 s−1) (compared to a freshwater input of 0.5 mSv). This study provides a first-order parameterization for the exchange at the mouth of glacial fjords for large-scale ocean models.
The genomic structure of isolation across breed, country and strain for important South African and Australian sheep populations
Authors: Nel Cornelius , Gurman Phillip , Swan Andrew , van der Werf Julius , Snyman Margaretha , Dzama Kennedy , Gore Klint , Scholtz Anna , Cloete Schalk 
Published: January 2022

Abstract
Background
South Africa and Australia shares multiple important sheep breeds. For some of these breeds, genomic breeding values are provided to breeders in Australia, but not yet in South Africa. Combining genomic resources could facilitate development for across country selection, but the influence of population structures could be important to the compatability of genomic data from varying origins. The genetic structure within and across breeds, countries and strains was evaluated in this study by population genomic parameters derived from SNP-marker data. Populations were first analysed by breed and country of origin and then by subpopulations of South African and Australian Merinos.

Results
Mean estimated relatedness according to the genomic relationship matrix varied by breed (-0.11 to 0.16) and bloodline (-0.08 to 0.06) groups and depended on co-ancestry as well as recent genetic links. Measures of divergence across bloodlines (FST: 0.04–0.12) were sometimes more distant than across some breeds (FST: 0.05–0.24), but the divergence of common breeds from their across-country equivalents was weak (FST: 0.01–0.04). According to mean relatedness, FST, PCA and Admixture, the Australian Ultrafine line was better connected to the SA Cradock Fine Wool flock than with other AUS bloodlines. Levels of linkage disequilibrium (LD) between adjacent markers was generally low, but also varied across breeds (r2: 0.14–0.22) as well as bloodlines (r2: 0.15–0.19). Patterns of LD decay was also unique to breeds, but bloodlines differed only at the absolute level. Estimates of effective population size (Ne) showed genetic diversity to be high for the majority of breeds (Ne: 128–418) but also for bloodlines (Ne: 137–369).

Conclusions
This study reinforced the genetic complexity and diversity of important sheep breeds, especially the Merino breed. The results also showed that implications of isolation can be highly variable and extended beyond breed structures. However, knowledge of useful links across these population substructures allows for a fine-tuned approach in the combination of genomic resources. Isolation across country rarely proved restricting compared to other structures considered. Consequently, research into the accuracy of across-country genomic prediction is recommended.
Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans
Authors: Mack Hildegard I. D. , Kremer Jennifer , Albertini Eva , Mack Elisabeth K. M. , Jansen-Dürr Pidder 
Published: January 2022

Abstract
Background
In the nematode Caenorhabditis elegans, longevity in response to germline ablation, but not in response to reduced insulin/IGF1-like signaling, is strongly dependent on the conserved protein kinase minibrain-related kinase 1 (MBK-1). In humans, the MBK-1 ortholog DYRK1A is associated with a variety of disorders, most prominently with neurological defects observed in Down syndrome. To better understand mbk-1’s physiological roles and their dependence on genetic background, we analyzed the influence of mbk-1 loss on the transcriptomes of wildtype and long-lived, germline-deficient or insulin-receptor defective, C. elegans strains by RNA-sequencing.

Results
mbk-1 loss elicited global changes in transcription that were less pronounced in insulin-receptor mutant than in germline-deficient or wildtype C. elegans. Irrespective of genetic background, mbk-1 regulated genes were enriched for functions in biological processes related to organic acid metabolism and pathogen defense. qPCR-studies confirmed mbk-1 dependent induction of all three C. elegans Δ9-fatty acid desaturases, fat-5, fat-6 and fat-7, in wildtype, germline-deficient and insulin-receptor mutant strains. Conversely, mbk-1 dependent expression patterns of selected pathogen resistance genes, including asp-12, dod-24 and drd-50, differed across the genetic backgrounds examined. Finally, cth-1 and cysl-2, two genes which connect pathogen resistance to the metabolism of the gaseous messenger and lifespan regulator hydrogen sulfide (H2S), were commonly suppressed by mbk-1 loss only in wildtype and germline-deficient, but not in insulin-receptor mutant C. elegans.

Conclusion
Our work reveals previously unknown roles of C. elegans mbk-1 in the regulation of fatty acid desaturase- and H2S metabolic-genes. These roles are only partially dependent on genetic background. Considering the particular importance of fatty acid desaturation and H2S for longevity of germline-deficient C. elegans, we propose that these processes at least in part account for the previous observation that mbk-1 preferentially regulates lifespan in these worms.
Stroke among highly active antiretroviral therapy-naive people living with the human immunodeficiency virus in China: a retrospective study of the characteristics, risk factors, and prognosis
Authors: Zhang Ling , Wang Yu , Xu Qiuhua , Zhang Wei , Liang Hongyuan , Wu Liang , Ni Liang , Gao Guiju , Yang Di , Zhao Hongxin , Xiao Jiang 
Published: January 2022

Abstract
Background
We aimed to clarify the characteristics, risk factors, and prognosis of stroke among HAART-naive people living with HIV (PLWH) in China.

Methods
We selected HAART-naive PLWH admitted to Beijing Ditan Hospital, Capital Medical University, from 1 January 2009 to 31 December 2019. Demographic and clinical data were obtained by searching an anonymous electronic case system. Descriptive analysis and logistic regression and Cox proportional hazard models were used to determine the characteristics and predictors of stroke among all HAART-naive PLWH and evaluate the risk factors of mortality in HAART-naive PLWH with stroke.

Results
Stroke was diagnosed in 105 cases (3.7%) of 2867 HAART-naive PLWH. Multivariate logistic regression indicated that age of 30–55 years (OR 1.903, 95% CI 1.005–3.603, p = 0.048), age of ≥ 55 years (OR 4.104, 95% CI 1.928–8.737, p < 0.001), and CD4 count of < 200 cells/µL (OR 2.005, 95% CI 1.008–3.985, p = 0.047) were associated with increased odds of stroke. Diabetes (OR 3.268, 95% CI 1.744–6.125, p < 0.001), hypertension (OR 2.301, 95% CI 1.425–3.717, p = 0.001), syphilis (OR 2.003, 95% CI 1.300–3.089, p = 0.002), and complicated AIDS-defining CNS diseases (OR 7.719, 95% CI 4.348–13.703, p < 0.001) were risk factors for stroke. Of the 105 stroke patients, 12 (11.4%) died during hospitalisation, and the risk factors for mortality among patients with stroke were age of > 65 years (AHR: 8.783, 95% CI 1.522–50.668, p = 0.015), complicated severe pneumonia (AHR: 3.940, 95% CI 1.106–14.029, p = 0.034), and AIDS-defining CNS diseases (AHR: 19.766, 95% CI 3.586–108.961, p = 0.001).

Conclusions
For HAART-naive people living with HIV (PLWH), stroke occurred in various age groups, and early screening for stroke, timely intervention for risk factors among patients in various age groups, and controlling the CD4 count are extremely important in reducing the burden of stroke.
Streptococcus agalactiae infective endocarditis in Canada: a multicenter retrospective nested case control analysis
Authors: Oravec Torrance , Oravec S. Annie , Leigh Jennifer , Matthews Liam , Ghadaki Bahareh , Mertz Dominik , Daley Peter , Shroff Anjali 
Published: January 2022

Abstract
Background
Infective endocarditis (IE) caused by Streptococcus agalactiae (GBS) is increasingly reported and associated with an aggressive course and high mortality rate. Existing literature on GBS IE is limited to case series; we compared the characteristics of patients with GBS IE to patients with GBS bacteremia without IE to identify risk factors for development of IE.

Methods
A nested case–control study in a cohort of adult patients with GBS bacteremia over a 18-year period was conducted across seven centres in three Canadian cities. A chart review identified patients with possible or definite IE (per Modified Duke Criteria) and patients with IE were matched to those without endocarditis in a 1:3 fashion. Multivariate analyses were completed using logistic regression.

Results
Of 520 patients with GBS bacteremia, 28 cases of possible or definite IE were identified (5.4%). 68% (19/28) met criteria for definite IE, surgery was performed in 29% (8/28), and the overall in-hospital mortality rate was 29% (8/28). Multivariate analysis demonstrated that IE was associated with injection drug use (OR = 19.6, 95% CI = 3.39–111.11, p = 0.001), prosthetic valve (OR = 11.5, 95% CI = 1.73–76.92, p = 0.011) and lack of identified source of bacteremia (OR = 3.81, 95% CI = 1.24–11.65, p = 0.019).

Conclusions
GBS bacteremia, especially amongst people who inject drugs, those with prosthetic valves, and those with no apparent source of infection, should increase clinical suspicion for IE.