bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in primary and metastatic epithelial ovarian cancer (EOC).
Authors: Mesnage Soizick Jeanne Lynette , Auguste Aurelie , Genestie Catherine , Dunant Ariane , Pain Erwann , Drusch Francoise , Gouy Sebastien , Morice Philippe , Bentivegna Enrica , Lhomme Catherine , Pautier Patricia , Michels Judith , Le Formal Audrey , Cheaib Bianca , Adam Julien , Leary Alexandra
Published: November 2019

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Background: Tumour immune response plays a critical role in progression and prognosis of EOC, however patterns of TILs and PD-L1 expression in primary and metastatic disease remain poorly described. Methods: Patients treated with neoadjuvant chemotherapy (NACT) for advanced EOC, between 2002-2014, and available sequential tumours (pre-NACT, post-NACT, or relapse) were retrospectively identified. Stromal TILs (sTILs) were evaluated according to the International TILs Working Group 2014 (Salgado 2015) on whole sections, and scored as a percentage of stromal area. Immune cell PD-L1 expression was evaluated by immunohistochemistry (E1L3N clone, Cell Signaling) in a smaller number of tumours. Cutoffs for analysis were: high sTILs ≥50%, PD-L1 positivity ≥5% membranous staining. Results: Among a total of 236 tumour samples from 150 patients (110 pre-NACT, 111 post-NACT, and 15 relapse tumours) median sTILs levels was significantly higher in metastatic tumours ( n=151) compared with primary tumours ( n=85) (median 30, IQR 10-50 vs. 15, IQR 5-30, p=0.0004). Among diagnostic samples, median sTILs level was 20 (IQR 10-45, n=85) in metastatic tumours compared with 10 (IQR 5-20, n =25) in primary tumours ( p=0064). Similarly in post-NACT samples, median sTILs level was 40 (IQR 15-60, n=51) in metastatic tumours compared with 20 (IQR 6.25-30, n=60) in primary tumours ( p=0026). Among relapse samples median sTILs level was 30 (IQR 10-50, n=15). Among all available samples ( n=97) PD-L1 positivity was detected in 33% (9/30) of primary and 50% (34/68) of metastatic tumours (Fisher’s exact test OR 2.3, 95%CI 0.94-5.4, p =0.08). Conclusions: In patients with EOC there is increased lymphocytic infiltration in both synchronous metastatic disease at diagnosis, and metachronous metastatic disease at relapse, compared with the primary tumour. This suggests increased immunogenicity as disease progresses. Furthermore, there is a trend towards upregulation of the PD-L1 immune checkpoint with disease progression.
Blood eosinophil counts as predictive marker in advanced melanoma patients treated with anti-PD1 therapies.
Authors: Gaba Lydia , Victoria Iván , Aya Francisco , Ruiz Gustavo , Pineda Estela , Reig Òscar , Fernandez-Martinez Aranzazu , Prat Aleix , Arance Ana
Published: November 2019

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Background: Anti-PD1 antibodies (Abs) Nivolumab (Nivo) and Pembrolizumab (Pembro) have both demonstrated to improve the overall survival (OS) in patients (pts) with advanced or metastatic melanoma (MM) in the first line setting. We previously reported that an increase in absolute eosinophil counts (AEC) of 100/mm3 over baseline at week 3 and an AEC > 400/mm3 at week 12 during anti-PD1 treatment (tmt) might identify pts with MM most likely to experience long-term disease control (1). AEC could serve as an important marker allowing the detection of those patients who may benefit from the therapy with anti-PD1 Abs. Methods: This retrospective observational study included pts with MM who received anti-PD1 tmt in a single institution. The objective was to identify whether an increase over the upper limit of normal AEC (>400/mm3) at any time during the tmt could predict better outcomes. Blood tests were performed before every tmt administration. Progression free survival (PFS) and OS were evaluated. Descriptive statistics were used to analyze patient baseline characteristics. PFS and OS were estimated by the Kaplan-Meier method. Results: From March 2013 to February 2016, 50 pts were treated with anti-PD1 Abs (39 pts with Pembro and 11 pts with Nivo). Median age was 58 years (33-84). 72% had received previous systemic tmt for MM, 64% had stage M1c disease, and 50% had elevated LDH levels. BRAF V600 mutations were observed in 34%. The median time to increase AEC > 400/mm2 was 42 (14-196) days. Pts who experienced an increase > 400/mm3 at 12 weeks demonstrated better outcomes in terms of PFS (21,9 [95% CI: 11,1-32,6] vs. 7,5 [95% CI: 4,3-10,7] months, p=0.017) and OS (38,0 [95% CI: 30,8-45,1] vs. 20,5 [95% CI: 15,7-25,3] months, p=0.025) compared with those who did not. Moreover, according to our previous results, pts with an increase of at least 100/mm3 in AEC over the baseline at 12 weeks also showed better OS (32,5 [95% CI: 26,3-38,8] vs. 16,3 [95% CI: 11,1-21,6] months, p=0.008). Conclusions: An increase in AEC of 100/mm3 over baseline and an absolute AEC > 400/mm3 at week 12 during anti-PD1 tmt might identify pts with MM most likely to experience clinical benefit with anti-PD1 Abs which could be relevant for pts management.
Correlation between dysthyroidism and efficacy in patients treated with anti PD-1 or anti PDL-1 agents.
Authors: Signorelli Diego , Cona Maria Silvia , Vitali Milena , Lo Russo Giuseppe , Proto Claudia , Imbimbo Martina , Zilembo Nicoletta , Platania Marco , Del Vecchio Michele , Seregni Ettore , Garassino Marina C , Di Nicola Massimo A. , De Braud Filippo G.
Published: November 2019

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Background: Immune checkpoints inhibitors have clearly improved patients’outcomes in different tumors, but definitive predictive biomarkers are still missing. Since thyroiditis have been reported, we have evaluated whether clinical responses are more frequent in patients who underwent anti PD-1 or anti PDL-1 agents and experienced dysthyroidism. Methods: We retrospectively evaluated 135 metastatic solid tumor patients, treated at our Institute with anti PD-1/PDL-1 antibodies since 2013. Thyroid toxicity was defined according to CTCAE version 4.0 and disease control (DC: CR+PR+SD) was chosen as efficacy endpoint. Correlation between dysthyroidism and DC rate was assessed by Fisher’s exact test. Results: Of 135 patients, 76 (56.3%) were treated by anti PD-1 and 59 (43.7%) by anti PDL-1 agents. Population was heterogeneous, including patients from the 1st to the 9th line of therapy, affected by the following cancers: 57 (42.2%) NSCLC, 18 (13.3%) melanoma, 13 (9.6%) RCC, 7 (5.2%) bladder and urothelial, 6 (4.5%) mesothelioma, 5 (3.7%) SCLC, 5 (3.7%) sarcoma, 5 (3.7%) biliary tract, 5 (3.7%) head and neck, 3 (2.2%) gastric, 3 (2.2%) colon, 2 (1.5%) Merkel cells and one each for thyroid, HCC, ovary, cervix, anal carcinoma and germ cells tumor. Median follow up was 8.6 months. Best responses were: 5 CR, 30 PR, 51 SD and 49 PD; 86 (63.7%) patients achieved DC. Overall, 38 patients developed dysthyroidism (subclinical, G1, G2 hypo/hyperthyroidism): 18/76 (23.7%) in anti PD-1, 20/59 (33.9%) in anti PDL-1 group; 31/38 (81.6%) of them achieved DC. The median time of dysthyroidism appearance was the 6th cycle of therapy (range 1st-22th). Of 97 patients who did not develop thyroid toxicity, 55 (56.7%) achieved DC. Dysthyroidism significantly correlated with DC rate (p=0.009). Conclusions: We found a significant correlation between dysthyroidism and clinical responses in solid tumor metastatic patients treated by anti PD-1 or anti PDL-1 antibodies. Our observation suggests that evaluation of thyroid function should be regularly performed during therapy with these agents. These retrospective findings must be confirmed in a prospective trial powered to see whether thyroid dysfunction is a surrogate marker of response.
In situ vaccination with local radiation and intratumoral immunocytokine to elicit a tumor-specific memory B-cell response.
Authors: Baniel Claire , Hank Jacquelyn A , Guy Emily I. , Gillies Stephen D , Korman Alan J. , Loibner Hans , Rakhmilevich Alexander L. , Harari Paul M. , Sondel Paul M. , Morris Zachary Scott
Published: November 2019

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Background: In a murine melanoma (MEL) model, we reported an in situ vaccination response to combined radiation (RT) and intra-tumor (IT) injection of anti-GD2 hu14.18-IL2 immunocytokine (IC). This treatment resulted in 71% complete regression of 5-week (~ 200mm3) tumors, a memory T cell response, and augmented response to systemic anti-CTLA-4 antibody (mAb) checkpoint blockade. We hypothesized that mice rendered disease-free (DF) by RT, IT-IC, and anti-CTLA-4 mAb might also exhibit a memory B cell response. Methods: C57BL/6 mice were implanted with 2x106 syngeneic, GD2+ B78 MEL cells and tumors developed for 5 weeks. Mice were treated with 12 Gy RT to this tumor followed by 5 daily IT injections of hu14.18-IL2 d6-10 after RT and IP injection of anti-CTLA-4 d3, 6, and 9 after RT. DF mice and naïve controls were challenged by subcutaneous implantation with 2x106 B78 MEL cells. Peripheral blood was collected from mice before and after B78 challenge and serum was evaluated for presence of tumor-specific mAbs using flow cytometry and ELISA. Results: Seventy-three percent of mice were rendered DF by treatment with RT, IT-hu14.18-IL2, and anti-CTLA-4. All of these (13/13) rejected a rechallange B78 implantation > 1 year later (range d378 – 511), whereas no naïve mice rejected B78 implantation (0/66). IgG from serum of DF mice bound selectively to B78 and parental GD2- B16 MEL cells and the level of this mAb response appeared to increase modestly d14 after B78 challenge. In naïve mice, a modest increase in tumor-specific mAb was identified between non-tumor implanted mice and d35 post-implantation mice (bearing tumors > 200mm3), however this level remained ~ 5 fold below that observed in DF mice prior to B78 rechallenge. In contrast, no appreciable mAb response was observed for unrelated syngeneic GD2+ Panc02 pancreatic tumor cells in serum of DF or naïve mice. Conclusions: We report an endogenous anti-tumor IgG humoral response in DF mice > 1 year after treatment with RT, IT-IC, and anti-CTLA-4 mAb, concurrent with demonstration of long lasting immune protection from re-challenge. Studies are underway to determine whether this response is involved in the therapeutic efficacy of this in situ vaccination regimen.
The landscape of the tumor-infiltrating B cell and its association with T-cell and tumor microenvironment in human cancers.
Authors: Chae Young Kwang , Bae William Han , Choi Yeonjoo , Kim Young Suk , Anker Jonathan Forrest , Giles Francis J.
Published: November 2019

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Background: Compared to recent advances in our knowledge of T cell biology with success of immunotherapy, little progress has been made in understanding of the effects of B cells in tumor microenvironment and their interactions with T cells. Preclinical studies reported that B cells may have immune suppressive roles in tumor microenvironment via induction of T cell exhaustion. However, this association has not been shown in human tissues. We explored the landscape of tumor infiltrating B and T cells and their association with tumor microenvironment in various human cancers for which the FDA approved the use of immune checkpoint inhibitors. Methods: Expression patterns for 812 immune related genes from the TCGA database were utilized to define tumor infiltrating cells in 2951 patients with bladder urothelial carcinoma, renal clear cell carcinoma, skin cutaneous melanoma, lung squamous cell carcinoma, lung adenocarcinoma, and head and neck squamous cell carcinoma. Odds ratios (ORs) of the numbers of tumors with versus without activated B cell infiltration by the presence of activated CD8T cell infiltration were calculated. Results: Immune landscape of the six human cancers showed a consistent inverse association between tumor infiltrating activated B and CD8 T cells (OR = 0.18, p < 0.001). B cell infiltration was associated with increased expressions of immune checkpoints PD-L1, PD-1 and CTLA-4 and regulatory cytokines TGF-β, IL-10 and IL-35, which are known to be secreted by regulatory B cells. Angiogenic markers, such as angiopoietins, VEGF, MMP-9, CXCL10, CXCL11 and Tie2, showed differential expression patterns between B cell high and low groups. Conclusions: This is the first study that reports the inverse association between tumor infiltrating B and CD8 T cells in human tissues. The strong associations between B cell infiltration and increased expressions of suppressive cytokines and immune checkpoints suggest regulatory B cells may play a role in the T cell suppression in tumor microenvironment. Our results implicate that depleting B cells, leading to possible disinhibition of T cell activation, may be a future therapeutic option in potentiating T cell mediated immunity.
Clonality of T-cell repertoire in the tumor microenvironment (TME) and peripheral blood of metastatic melanoma patients treated with CTLA4 blockade and interferon-α (IFN).
Authors: Tarhini Ahmad A. , Agha Aya , Rahman Zahra , Benzeno Sharon , Yusko Erik , Vallabhaneni Priyanka
Published: November 2019

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Background: Patients with metastatic melanoma were treated with tremelimumab and IFN in a previously reported study (Tarhini. J Clin Oncol. 2012). Clonality of T-cell repertoire was analyzed in terms of clinical response both in TME and in peripheral blood. Methods: Patients received tremelimumab 15 mg/kg I.V. every 12 weeks. High dose IFN (HDI) was administered concurrently. Responses were assessed by RECIST as complete (CR) or partial (PR), stable disease (SD) or progression (PD). T-cell receptor beta chain (TCRB) repertoire was immunosequenced in peripheral blood mononuclear cells (PBMC) (N=33 patients) and tumor (N=18) utilizing Adaptive Biotechnologies immunoSEQ platform to determine repertoire clonality and T-cell fractions at pre-treatment (tumor, PBMC), one month (PBMC), and 3 months (PBMC). The clonality metric quantitates, the extent of mono- or oligo-clonal expansion by measuring the shape of the clone frequency distribution. Values range from 0 to 1; values approaching 1 indicate a nearly monoclonal population. Results: In pretreatment TME, T-cell clonality was significantly (p = 0.0008) different and greater in patients who achieved disease control (CR, PR, SD) versus those with PD. Further, there was a significant (p = 0.044) difference between the increased TCR fraction in TME in responders (CR, PR) and non-responders (SD, PD). There was a trend towards association between pretreatment TME T-cell clonality and overall survival (OS) (p = 0.24) and progression free survival (PFS) (p = 0.18) not reaching significance. Within the circulation (PBMC), no significant associations were found by examining the pretreatment samples. However, early on-treatment (day 29) there was significant association and decrease in T-cell clonality and OS (p = 0.005) and PFS (p = 0.003). Conclusions: T-cell clonality in the TME pretreatment is a promising biomarker of immunotherapeutic benefit in our study. While baseline PBMC clonality was not associated with clinical benefit, early on-treatment (day 29) was significantly associated. These findings require validation in an independent cohort and exploration in relation to other immunotherapeutics. Clinical trial information: NCT00610857.
Experience of immune-related adverse events associated with ipilimumab and nivolumab in a single center.
Authors: Rapoport Bernardo Leon , Smit Teresa , van Eeden Ronwyn
Published: November 2019

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Background: Anti-programmed cell death receptor-1 (PD-1) and anti-CTLA4 antibodies represent an effective anti-cancer. Ipilimumab and nivolumab can induce immune-related adverse events (IrAEs). These IrAEs affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Life-threatening and fatal irAEs have been reported; adequate diagnosis and management are essential. Methods: A retrospective review of data from 40 patients (pts) records were used to describe the IrAE’s associated with 15 pts treated with ipilimumab and 25 pts treated with nivolumab. Results: A total of 40 pts (25 males and 15 females) were included in the analysis. The median age was 63 years (range 30 - 85 years). The performance status (PS) ranged from 0 to 2, with a median PS of 1. In total, 3 pts with metastatic melanoma, 18 with non small cell lung cancer (NSCLC), 2 with renal cell carcinoma and 2 with Hodgkin’s disease were treated with nivolumab and 15 with metastatic melanoma received ipilimumab. A total of 167 cycles of nivolumab (median = 4, range 1-16) and 60 cycles of ipilimumab (median = 4 cycles, range 1-4 cycles) were administered. Seven IrAEs are described in 19 pts treated with ipilimumab. These include endocrinopathy in 3 pts (hypophysitis in pt and hyphothyroidsm in 2 pts), colitis in 3 pts (1 required infliximab) and hepatitis in 1 pt. Among the pts treated with nivolumab 7 IrAEs were documented. These included pneumonitis in 2 pts, skin rash in 3 pts, mild diarrhea in 1 pt and mild uveitis in 1 pt. Additionally, 3 chest infections were documented including a case of pulmonary tuberculosis in a pt with NSCLC. Conclusions: Anti-PD1 and anti-CTLA4 antibodies can induce a plethora of irAEs. Colitis was more common with ipilimumab while pneumonitis more common with nivolumab. The knowledge of IrAE’s will allow prompt diagnosis and improve the management resulting in decreased morbidity.
Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials
Authors: DeSouza Cyrus , Cariou Bertrand , Garg Satish , Lausvig Nanna , Navarria Andrea , Fonseca Vivian
Published: November 2019

Context

Variations in the prevalence and etiology of type 2 diabetes (T2D) across race and ethnicity may affect treatment responses. Semaglutide is a glucagon-like peptide-1 analog approved for once-weekly, subcutaneous treatment of T2D.

Objective

To compare semaglutide efficacy and safety in race and ethnicity subgroups across the SUSTAIN trials.

Design

Post hoc analysis of data from phase 3 randomized SUSTAIN 1–5 and 7 (pooled), and SUSTAIN 6 trials.

Participants

3074 subjects (SUSTAIN 1–5 and 7) and 1648 subjects (SUSTAIN 6).

Interventions

Semaglutide 0.5 or 1.0 mg, placebo, or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine 100IU/ml and dulaglutide 0.75 or 1.5 mg).

Main Outcome Measures

Change in hemoglobin A1C (HbA1c) and body weight from baseline to weeks 30, 40 and 104, and other efficacy and safety endpoints.

Results

HbA1c was reduced from baseline by 1.0 to 1.5 percentage points and 1.3 to 2.0 percentage points, and body weight was reduced by 2.3 to 4.7 kg and 3.6 to 6.1 kg with semaglutide 0.5 and 1.0 mg, respectively, across race and ethnicity subgroups. Minor changes in blood pressure and lipid profiles were observed. Adverse events (AEs) were reported in similar proportions of subjects across trials. More Asian versus other race subgroups discontinued treatment prematurely due to AEs. The most commonly reported AEs were gastrointestinal disorders.

Conclusions

In this SUSTAIN trials post hoc analysis, semaglutide was associated with consistent and clinically relevant reductions in HbA1c and body weight in subjects with T2D, with minor variations in efficacy and safety outcomes associated with race or ethnicity.
Infiltration Between Popliteal Artery and Capsule of the Knee Block to Augment Continuous Femoral Nerve Catheter for Adolescent Anterior Cruciate Ligament Reconstruction: A Case Series
Authors: Nguyen Kim T. , Marcelino Ryan , Jagannathan Narasimhan , Suresh Santhanam , Sawardekar Amod
Published: November 2019

Infiltration between popliteal artery and capsule of the knee (IPACK) is a novel technique that can provide additional analgesic relief, although there are no studies to date in the adolescent population. In 3 adolescent patients undergoing anterior cruciate ligament surgery, IPACK block augmented continuous femoral nerve block by providing posterior knee analgesia with no or only minimal opioid needs in the post-anesthesia care unit and did not produce sciatic motor weakness.
Teaching the Environmental Humanities
Authors: O’Gorman Emily , van Dooren Thom , Münster Ursula , Adamson Joni , Mauch Christof , Sörlin Sverker , Armiero Marco , Lindström Kati , Houston Donna , Pádua José Augusto , Rigby Kate , Jones Owain , Motion Judy , Muecke Stephen , Chang Chia-ju , Lu Shuyuan , Jones Christopher , Green Lesley , Matose Frank , Twidle Hedley , Schneider-Mayerson Matthew , Wiggin Bethany , Jørgensen Dolly
Published: November 2019

This article provides the first international overview and detailed discussion of teaching in the environmental humanities (EH). It is divided into three parts. The first offers a series of regional overviews: where, when, and how EH teaching is taking place. This part highlights some key regional variability in the uptake of teaching in this area, emphasizing important differences in cultural and pedagogical contexts. The second part is a critical engagement with some of the key challenges and opportunities that are emerging in EH teaching, centering on how the field is being defined, shared concepts and ideas, interdisciplinary pedagogies, and the centrality of experimental and public-facing approaches to teaching. The final part of the article offers six brief summaries of experimental pedagogies from our authorship team that aim to give a concrete sense of EH teaching in practice.
Trans/Coalitional Love-Politics
Authors: Chaudhry V Varun
Published: November 2019

This essay works at the intersection of black feminism and trans studies to reflect on the radical possibilities for the futures of transgender studies and politics. Drawing on ethnographic data with a large-scale LGBTQ service organization, and focusing specifically on an example of the backlash that a black cisgender- and queer-identified woman received for coordinating a transgender-focused event, the article interrogates the ways in which the cisgender/transgender binary, pervasive in trans studies and trans organizing, counterintuitively reinforces the racialized gendered subjugation of black women. To circumvent the subjugation of black feminine bodies and thus harness the radical potential of trans studies and organizing, the author proposes a conception of trans coalitional love-politics. This is a reading and political practice that explodes the cis/trans binary and thus imagines more robust possibilities for racialized gendered justice.
Deviant Care for Deviant Futures
Authors: Hwang Ren-yo
Published: November 2019

This article introduces the concept of carceral care as those public-facing “do-better” penal practices, policies, and material actions used to ward off future investigation of underlying institutional violences of carceral spaces. As a model for denaturalizing carceral care, time, space, and the perpetuity of reform, it explores theories of deviant care, mutual aid, and QTBIPoC radical relationalism. It investigates how inhabiting deviance is a necessary care practice as modeled every day by queer bonds of survival, particularly from within the confines of carceral spaces. Based on relationships built over the last four years with trans women of color organizing inside a “male-designated” state prison in Corcoran, California, this article connects questions of deviant care as the refusal of the diagnosable and individuated self through queer black/indigenous feminist of color resistance and radical thought.
Synthesis and maintenance of lipid droplets are essential for mouse preimplantation embryonic development
Authors: Aizawa Ryutaro , Ibayashi Megumi , Tatsumi Takayuki , Yamamoto Atsushi , Kokubo Toshiaki , Miyasaka Naoyuki , Sato Ken , Ikeda Shuntaro , Minami Naojiro , Tsukamoto Satoshi
Published: November 2019

Lipid droplets (LDs), which are ubiquitous organelles consisting of a neutral lipid core coated with a phospholipid monolayer, play key roles in the regulation of cellular lipid metabolism. Although it is well known that mammalian oocytes and embryos contain LDs and that the amount of LDs varies among animal species, their physiological functions remain unclear. In this study, we have developed a method based on two-step centrifugation for efficient removal of almost all LDs from mouse MII oocytes (delipidation). We found that delipidated MII oocytes could be fertilized in vitro, and developed normally to the blastocyst stage even when the embryos were cultured in the absence of a fatty acid supply. LDs were newly synthesized and accumulated soon after delipidation, but chemical inhibition of long chain acyl-CoA synthetases (ACSLs) blocked this process, resulting in severe impairment of early embryonic development. Furthermore, we found that overabundance of LDs is detrimental to early embryonic development. Our findings demonstrate the importance of synthesis and maintenance of LDs, mediated in part by ACSL activity, during preimplantation embryonic development.
Does Diversity Matter for Health? Experimental Evidence from Oakland
Authors: Alsan Marcella , Garrick Owen , Graziani Grant
Published: November 2019

We study the effect of physician workforce diversity on the demand for preventive care among African American men. In an experiment in Oakland, California, we randomize black men to black or non-black male medical doctors. We use a two-stage design, measuring decisions before (pre-consultation) and after (post-consultation) meeting their assigned doctor. Subjects select a similar number of preventives in the pre-consultation stage, but are much more likely to select every preventive service, particularly invasive services, once meeting with a racially concordant doctor. Our findings suggest black doctors could reduce the black-white male gap in cardiovascular mortality by 19 percent. (JEL I12, I14, C93)
A hidden lung cancer in a patient with granulomatosis with polyangiitis
Authors: Xie Cheng , Stoddart Catriona , Bewes James , Peschl Heiko , Luqmani Raashid , Benamore Rachel
Published: November 2019

Granulomatosis with polyangiitis is a systemic necrotizing vasculitis that affects the small- and medium-sized blood vessels. The diagnosis can be challenging since the clinical and imaging findings have similarities with infection, and malignancy. Serologic and histopathological investigations often help confirm the diagnosis. However, this can be falsely reassuring. We present a unique case of the coexistence of vasculitis and squamous cell carcinoma in the same cavitating lung mass. The case highlights the importance of recognizing changes in disease behaviour early to allow for timely management.
Multifaceted circuit functions of adult-born neurons
Authors: Dieni Cristina V. , Gonzalez Jose Carlos , Overstreet-Wadiche Linda
Published: November 2019

The dentate gyrus continually produces new neurons throughout life. Behavioral studies in rodents and network models show that new neurons contribute to normal dentate functions, but there are many unanswered questions about how the relatively small population of new neurons alters network activity. Here we discuss experimental evidence that supports multiple cellular mechanisms by which adult-born neurons contribute to circuit function. Whereas past work focused on the unique intrinsic properties of young neurons, more recent studies also suggest that adult-born neurons alter the excitability of the mature neuronal population via unexpected circuit interactions.
Functional and proteomic analysis of a full thickness filaggrin-deficient skin organoid model
Authors: Elias Martina S. , Wright Sheila C. , Nicholson William V. , Morrison Kimberley D. , Prescott Alan R. , Ten Have Sara , Whitfield Phillip D. , Lamond Angus I. , Brown Sara J.
Published: November 2019

Background:Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ that can be modelled using primary cellsin vitroprovides the opportunity for selected genetic effects to be investigated in detail.

Methods:Primary human keratinocytes and donor-matched primary fibroblasts from healthy individuals were used to create skin organoid models with and without siRNA-mediated knockdown ofFLG. Biological replicate sets of organoids were assessed using histological, functional and biochemical measurements.

Results:FLGknockdown leads to subtle changes in histology and ultrastructure including a reduction in thickness of the stratum corneum and smaller, less numerous keratohyalin granules. Immature organoids showed some limited evidence of barrier impairment withFLGknockdown, but the mature organoids showed no difference in transepidermal water loss, water content or dye penetration. There was no difference in epidermal ceramide content. Mass spectrometry proteomic analysis detected >8000 proteins per sample. Gene ontology and pathway analyses identified an increase in transcriptional and translational activity but a reduction in proteins contributing to terminal differentiation, including caspase 14, dermokine, AKT1 and TGF-beta-1. Aspects of innate and adaptive immunity were represented in both the up-regulated and down-regulated protein groups, as was the term ‘axon guidance’.     

Conclusions:This work provides further evidence for keratinocyte-specific mechanisms contributing to immune and neurological, as well as structural, aspects of skin barrier dysfunction. Individuals with filaggrin deficiency may derive benefit from future therapies targeting keratinocyte-immune crosstalk and neurogenic pruritus.
Assessment of the quality of life after surgical treatment of patients with primary postoperative ventral hernia in conditions of comorbidity
Authors: Piatnochka V. I. , Kornaha S. I. , Kohan R. S.
Published: November 2019

Improving the quality of life of patients after surgical treatment of primary and postoperative ventral hernias is a very urgent problem, which is explained by the increasing number of patients with this pathology, high rates of recurrences and complications in hernioplasty (4.3–46 %).Objective. Improving the results of surgical treatment of patients with primary and postoperative ventral hernia under comorbidity by performing a comparative evaluation of different types of hernioplasty performed using quality of life indicators in the early and late postoperative period.Materials and methods. The quality of life indicators were analyzed based on the SF-36 questionnaire after surgical treatment of 1419 patients with primary and postoperative ventral hernia under conditions of comorbidity, operated with patient’s own tissue hernioplasty, onlay, sublay, inlay, CST techniques. The total number of patients questioned on the SF-36 questionnaire on quality of life was527. In relation to all patients operated on by different methods of hernioplasty in the main group and comparison group (1419 persons), the number of patients questioned in the postoperative period was 37.14 %, ie more than a third of all patients operated for the whole period of the study (2001–2017). pp). This demonstrates the representativeness of this sample population.Results. The results of the study were found to be the most optimal for the use in the surgical treatment of primary ventral hernia (PVH) and postoperative ventral hernia (POVH) sublay and inlay technique, taking into account the lowest incidence of recurrence in their performance and the fastest recovery of the basic parameters of life of patients and quality of life in the postoperative period.The indicators of physical and psychological components of health at this time of the survey were significantly higher in patients of the main group. This is probably due to the recorded recurrence of PVH [8] after own tissue hernia. Determination of health components after 1 year showed a slight improvement in both indicators relative to the previous survey data in all study groups (p <0.05).The psychological component of health was significantly higher in patients in the main group than in patients in the comparison group. (51.73±6.37) points compared with the results of the 6-month survey, and slightly improved ((46.81±2.59) points) in the comparison group (p> 0.05).Conclusions. The results of the study seriously suggest that there is a strong correlation between the type of surgical hernioplasty techniques used in patients with  PVH and POVH the incidence of disease recurrence and, as a consequence, the quality of life of patients – an important comprehensive determinant of health.
A review of ketorolac as a prehospital analgesic
Authors: Mallinson Tom Edward
Published: November 2019

The provision of multimodal analgesia is a core concept in the management of acute and chronic pain. In the prehospital setting, non-steroidal anti-inflammatory drugs (NSAIDs) can be used alongside paracetamol and opioids to provide such analgesia. Ketorolac is an NSAID which can be administered by injection and is used internationally in civilian and military prehospital care. This CPD article discusses Ketorolac as an analgesic option for paramedics.
Unpacking overload: Examining the impact of content characteristics and news topics on news overload
Authors: Lee Angela M. , Holton Avery , Chen Victoria
Published: November 2019

The proliferation of digital media has provided the public with an abundance of information and pathways to engage with that information. Alongside the opportunities offered by this wealth of content exist feelings of, and worries over, news and information overload. Research has indicated
that to respond to this issue, some news consumers proactively scan the news. When such activity fails, or in some cases before it ever begins, other news consumers disconnect from the news altogether. Through a non-random online survey, this study advances empirical understandings of the
news overload and individuals' responses to that overload by proposing a more holistic way to measure news overload. By examining the ways in which content characteristics and news topics influence individuals' feelings of overload and how scanning or avoidance of and from the news may result,
this study finds that information overload, and news overload more specifically, can be connected to the characteristics of news content and the topic of coverage.
Hypertextuality in net-native health news: A quantitative content analysis of hyperlinks and where they lead to
Authors: Stroobant Joyce , Raeymaeckers Karin
Published: November 2019

By means of a quantitative content analysis of two Belgian net-native health news websites, this article investigates the reliability and usability of the hyperlinks in various forms of online news. Hyperlinks in our sample overwhelmingly redirect readers to government websites and
websites that contain scientific information such as websites of universities, scientific research groups and peer-reviewed academic journals. Hyperlinks to information generally perceived as less reliable and possibly biased such as user-generated content or pharmaceutical companies are used
rarely. This suggests that online health journalists strongly share the preferences of their offline colleagues. However, in terms of the potential of hypertext to tailor health news to the needs of the audience, for instance by including multimedia content or even simply by hyperlinking to
webpages in the same language as the original, there are clear indications that Belgian online net-native health news falls short. The practical hindrances and hurdles identified in this content analysis constitute an invitation for online health journalists to consider the possibilities of
hypertext in the light of how users might appreciate this practice.
From melancholic to happy immigrant: Staging simpleton in the comedies of migration
Authors: Meerzon Yana
Published: November 2019

This article examines devices of comedy, laughter and dramatic humour as technologies of ethics when it comes to staging migration in contemporary theatre. Looking at a tragic farce Hunting Cockroaches (1985), written by the Polish theatre artist Janusz Głowacki during his American exile, and a domestic melodrama , written by a Korean Canadian Ins Choi, this article examines comedy as a particular dramatic model that can challenge staging migrants as agentless and voiceless victims. It asks, what happens when theatre artists begin to use stereotype to stage the trauma of displacement? To what extent is comedy truly capable of rendering the complexity of migration? And how ethical can the comedic representation of a migrant be?
RUMPUT LAUT: ANTIOKSIDAN ALAMI PENANGKAL RADIKAL BEBAS
Authors: Dwimayasanti Rany
Published: November 2019

SEAWEED: NATURAL ANTIOXIDANT FREE RADICAL ANTIDOTE. Free radicals are the result of various complex chemical processes in the body, in form of oxidation process, cell metabolism, UV irradiation, environmental pollution such as cigarette smoke, and other pollutants. The effects of free radicals can be prevented by addition of antioxidants endogenously from outside the body. Seaweed is one source of natural antioxidants that is safe for the body. Seaweed contains bioactive compounds that are able to prevent free radicals such as carotenoids, phenols, vitamins and minerals.
ASPEK BIOLOGI DAN ABLASI MATA PADA UDANG WINDU Penaeus monodon SUKU PENAEIDAE (DECAPODA: MALACOSTRACA)
Authors: Pratiwi Rianta
Published: November 2019

THE ASPECTS OF BIOLOGY ANDEYE ABLATION ON SHRIMP Penaeus monodon PENAEIDAE (DECAPODA: MALACOSTRACA). A qood quality of seeds (fry) is a very important production component to support the shrimp farming activities in ponds. The quantity and quality of shrimp seeds are largely determined by hatchery products obtained from the quality of the broodstock used. The provision of the broodstock is the beginning of the seed production activities and is one of the factors that determines the quality and quantity of the production. The growing demand for mature gonad shrimp is a big problem for shrimp farmers, due to the ability of windu shrimp to spawn in the nature (ripe gonad naturally) takes relatively long time. Therefore, the eye ablation process can accelerate the process of gonad maturity. This article describes some aspects that should be understood in conducting windu shrimp farming as well as explanations of ablation process.
UMA ANÁLISE DOS FATORES INFLUENCIADORES PARA A ADOÇÃO DO MOBILE BANKING NO BRASIL
Authors: MOREIRA NAAMÃ , CHAVES MARCIRIO SILVEIRA , BIGNETTI BERNARDO
Published: November 2019

Os avanços tecnológicos no ambiente bancário têm provocado mudanças relevantes nos serviços fornecidos a clientes. As instituições passaram a disponibilizá-los via canais alternativos, como o mobile banking. No entanto, ainda há resistências quanto ao seu uso. Este trabalho analisa quais são os fatores que influenciam a adoção do mobile banking no contexto brasileiro. Mediante a natureza quantitativa da pesquisa, usou-se um survey (n=411) para a coleta de dados. A análise dos fatores influenciadores foi realizada com base no modelo UTAUT. Os resultados evidenciam a expectativa de desempenho, a credibilidade percebida e a intenção de uso como os principais fatores de influência na adoção e no uso de mobile banking no Brasil. Esta pesquisa adiciona um trabalho empírico ao uso do modelo UTAUT aplicado ao mobile banking no Brasil. Como contribuição prática, os gestores de banco podem direcionar e ampliar os investimentos para: ofertar mais produtos e serviços via aplicativo e implementar melhorias; manter o foco na segurança digital bancária; e desenvolver estratégias de marketing, a fim de influenciar a intenção do comportamento de uso do mobile banking.
IDENTIDADE DA GERAÇÃO Z NA GESTÃO DE STARTUPS
Authors: MELO ARIANA DE OLIVEIRA , TAVARES MARUZA VIEIRA BARBOZA , FELIX BRUNA DE SOUSA , DOS SANTOS ANA CRISTINA BATISTA
Published: November 2019

O presente artigo visa compreender a identidade da geração Z na gestão de startups. Para a pesquisa exploratória de natureza qualitativa, utilizou-se a entrevista semiestruturada na coleta de dados, havendo, ainda, aplicação de exercício-estímulo. Como sujeitos de pesquisa, compreenderam cinco líderes de startups já atuantes no mercado pertencentes à geração Z. Uma análise dos dados foi realizada com o apoio do software Atlas TI. Os resultados mostram que as características atribuídas à geração Z que mais influenciam na gestão são a autoconfiança, o otimismo, o imediatismo, a capacidade de serem multitarefas e a preocupação em buscar a satisfação no trabalho, fazendo o que se gosta e encarando os desafios como etapa inerente ao sucesso. Além desses, surgem, como novos traços dos gestores “Zs”, a coragem e a impulsividade, além de evidências de otimismo e confiança. O fator idade justifica possíveis erros de gestão, reforçando a importância de uma hierarquia horizontal. Os entrevistados falam de startups como tipos alinhados ao desenvolvimento do espírito empreendedor dessa geração. Por outro lado, fogem do padrão de representação de startups como dependentes apenas de uma ideia inovadora e alertam para a necessidade de conhecimento, experiência, bom gerenciamento, boa rede de contatos e trabalho em equipe.
SOBRE AS PRÁTICAS “INVISÍVEIS” DA DOCÊNCIA: OLHARES A PARTIR DE PRESSUPOSTOS DA HISTÓRIA CULTURAL
Authors: Souza Nathália Cristina Amorim Tamaio de
Published: November 2019

Neste ensaio é realizada uma discussão em torno das práticas “invisíveis” da docência. Trata-se de um estudo de natureza teórica, construído a partir de inquietações da autora sobre a sutileza das práticas cotidianas assumidas pelos professores face a situações de controle às quais são submetidos constantemente. A abordagem conceitual reside nos pressupostos da História Cultural, mais especificamente nas contribuições de Michel de Certeau, Michelle Perrot, Anne-Marie Chartier e Carlo Ginzburg, para fundamentar as proposições suscitadas. Como principal apontamento, ressalta-se que mesmo a docência sendo exercida em meio a subordinações, o professor sempre lançará mão de apropriações, desvios e reempregos ao realizar ações pautadas em seus modos próprios de fazer. Presume-se que é para essas ações, geralmente negligenciadas, que precisamos voltar nossos olhares para entendermos as sinuosidades presentes no fazer docente.
OS CONCEITOS DE INTELIGÊNCIA E DE DEFICIÊNCIA INTELECTUAL: AS MESMAS ORIGENS?
Authors: Caetano Andressa Mafezoni , Pletsch Márcia Denise
Published: November 2019

Neste artigo discutem-se as origens dos conceitos de inteligência e de deficiência intelectual a partir do contexto europeu e suas influências no cenário escolar brasileiro. Trata-se uma pesquisa bibliográfica com base nos estudos de Alfred Binet sobre a medida de inteligência e “anormalidade” em diálogo com a literatura científica contemporânea. A partir das análises realizadas, evidenciamos a influência do debate europeu na Educação Especial brasileira. Como considerações finais, mostramos que esses conceitos têm as mesmas origens e foram forjados no contexto de uma ciência médico-psicológica, justificada por um ideário republicano como “solução” dos problemas educacionais brasileiros da época.
Public Schools' Identification and Management of Underage Alcohol Use: A Qualitative Study
Authors: Robison William Theodore , Soares Mary H. , Meca Alan , Jean-Jacques Jennifer , Tubman Jonathan G. , Schwartz Seth J.
Published: November 2019

Objective: In this qualitative study, we investigated how public schools in the Miami-Dade County School District identify and manage students' underage alcohol use and to explore the benefits and challenges of systematic screening for underage alcohol use in district schools.
Methods: We conducted face-to-face interviews with 16 school officials directly responsible for addressing underage alcohol use incidents at district middle and high schools. These individuals included assistant principals, guidance counselors, social workers and school-based health-care
professionals. A grounded-theory approach was used to code and synthesize informants' responses. Results: No informants reported systematic screening for underage alcohol use at their schools, although their middle and high schools employed a range of intervention strategies. Emergent
themes reflected common ways by which students using alcohol were identified, factors influencing underage alcohol use, and barriers to screening intervention implementation. Lack of access to acute intoxication events, differing policies across schools, inadequate resources, and reliance
on administrator discretion rather than explicit policy mandates appear to undermine the development of consistent strategies for addressing suspected or reported underage alcohol use. Conclusion: Public schools may serve as key implementation contexts for future universal or selected
screening initiatives to identify and manage cases of underage alcohol use. The benefits and challenges perceived by school staff and administrators – especially for implementing consistent policies across schools – are critical to the development of acceptable, feasible, and sustainable
alcohol screening initiatives.
Strategies to digitalize inert health practices: The gamification of glucose monitoring
Authors: Neumann Caterina Joelle , Kolak Tereza , Auschra Carolin
Published: November 2019

The ongoing digital transformation will potentially change traditional health care practices fundamentally. However, change agents usually face serious challenges arising from the highly institutionalized nature of this industry. Using the gamification of glucose monitoring as part of diabetes care as an example, this paper focuses on strategies to transform health care, allowing not only to cope with, but also to change this context: gamification encourages behavioral changes in patients, establishes new roles between patients and providers, and thereby elevates patient empowerment.
On the spectrum of an infinite-order differential operator and its relation to Hamiltonian mechanics
Authors: Akrami Seyed Ebrahim
Published: November 2019

We introduce an infinite-order linear differential operator and study its spectrum.
We show that all analytical functions around the origin are its eigenfunctions corresponding to zero eigenvalue.
We outline an interesting relation between this operator and the conservation law of energy in Hamiltonian mechanics.
On the Thermodynamics of Micellizationof Oppositely Charged Surfactants in the Presence of Organic Additives in the Aqueous Medium
Authors: Kumar Girish , Chauhan Mohinder Singh , Kumar Anil
Published: November 2019

To investigate the effect of additives urea and thiourea, on the micellization behavior of sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB), detailed conductance measurements were carried out in aqueous media at different temperatures. The critical micelle concentration (CMC), determined from the discontinuity in the plots of molar conductance versus square root of concentration, indicated an inhibitory effect of urea and thiourea on micelle forming ability of the surfactants SDS and CTAB in the range of composition studied. The demicellizing effect of urea has been found to be more pronounced in SDS than CTAB. These observations are further augmented by the evaluation of thermodynamic parameters of micellization. A negative change in enthalpy of micellization (

Δ

H
m
∘

$\Delta{\text{H}}_{\text{m}}^{\circ}$

) indicates a strong interaction between water and the additives and a positive change observed in entropy of micellization (

Δ

S
m
∘

$\Delta{\text{S}}_{\text{m}}^{\circ}$

) manifest, that the micellization is an entropy-driven process. Further

Δ

H
m
∘

$\Delta{\text{H}}_{\text{m}}^{\circ}$

and

Δ

S
m
∘

$\Delta{\text{S}}_{\text{m}}^{\circ}$

change in mutually compensating manner, so that

Δ

G
m
∘

<
0

$\Delta{\text{G}}_{\text{m}}^{\circ} < 0$

is not significantly affected. Finally, the counterion binding values (β) obtained for SDS and CTAB remain practically constant from 0.6 to 0.8 between 25 °C and 45 °C indicate that the size and shape of micelle remain essentially constant. Moreover, the increase in

Δ

G
II
∘

$\Delta{\text{G}}_{{\text{II}}}^{\circ}$

values, which represent the effect of co-solvent or additive on micellization, substantiates the above observations. Many early works has investigated the micellization behavior of surfactants using a fixed additive composition. However, in this study, variable aqueous compositions of urea (0.30–1.78 wt%) and thiourea (0.24–1.41 wt%) have been considered.