bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of overweight, obesity, and post-treatment weight changes on occupational reintegration of breast cancer (BC) survivors.
Authors: Di Meglio Antonio , Menvielle Gwenn , Dumas Agnes , Gbenou Arnauld S. , Bovagnet Thomas , Martin Elise , Ferreira Arlindo R. , Vanlemmens Laurence , Arsene Olivier , Ibrahim Mahmoud , Wassermann Johanna , Martin Anne-Laure , Lemonnier Jerome , Del Mastro Lucia , Jones Lee , Partridge Ann H. , Ligibel Jennifer A. , Andre Fabrice , Michiels Stefan , Luis Ines Maria Vaz Duarte
Published: March 2020

11562

Background: Overweight and obesity are strongly linked to poorer BC-specific outcomes, quality of life and financial burden in cancer care. Weight loss interventions have the potential to improve such outcomes. Fewer data exist on whether excess weight and post-diagnosis weight changes impact the ability of BC survivors to return to work (RTW). Methods: CANTO (NCT01993498) is a multicenter prospective longitudinal study of 12000 patients (pts) with stage I-III BC that characterizes long-term toxicities of BC treatment. Of 5801 pts enrolled from 2012-2014 (last data lock), we identified 1874 pts who were professionally active at BC diagnosis, ≥5 years (yrs) younger than minimum legal retirement age (62 yrs) and with updated work status 2 yrs after diagnosis. Logistic regression models evaluated the impact of body mass index (BMI) at diagnosis and of weight changes over 2 yrs after diagnosis on odds of non-RTW, adjusting for age, education, income, BC treatment and recreational physical activity (PA). Results: 37% pts were overweight or obese at diagnosis (BMI ≥25 kg/m2): 34% of them gained ≥5% and 16% lost ≥5% weight after diagnosis. Rates of non-RTW at 2 yrs were significantly higher in overweight or obese vs under or normal weight pts (27% vs 18%, p≤.001; adjusted odds ratio 1.37, 95% Confidence Interval [CI] 1.04-1.80, p = .017). Overweight and obese pts who did not RTW experienced higher increments in weight (mean [95% CI]: +3.6% [+2.3, +4.9] vs +1.5% [+0.8, +2.2]) and reported more modest changes in PA (mean [95% CI]: +1.0 [-1.4, +3.5] vs +2.1 [+0.8, +3.3] MET-h/week) vs those who did RTW. Weight changes independently impacted odds of non-RTW in overweight and obese pts (p for interaction weight change*BMI ≤.001): a 5% weight gain was associated with 17% increase in adjusted odds of non-RTW (95% CI 2-35%, p = .024), whereas a loss ≥5% with 60% reduced odds of non-RTW vs weight gain (95% CI 18-82%, p = .013). Conclusions: Excess weight and weight changes are significantly associated with occupational reintegration after BC in overweight and obese pts. Randomized studies testing dedicated weight control interventions should also measure outcomes of social rehabilitation in this large subset of survivors. Clinical trial information: NCT01993498.
Second solid (SMN) and hematologic malignant neoplasms (HMN) among 24,900 United States testicular cancer survivors (TCS) after chemotherapy (CHEM), radiotherapy (RT), or surgery only (SURG).
Authors: Abu Zaid Mohammad Issam , Milano Michael T. , Dinh Paul C , Fosså Sophie , Yang Hongmei , Feldman Darren R. , Travis Lois B. , Fung Chunkit
Published: March 2020

11573

Background: No large, population-based U.S. study has comprehensively examined SMN and HMN risks after TC, taking into account initial therapy and focusing on recent decades. Methods: Standardized incidence ratios (SIR) for SMN and HMN stratified by site and time since TC diagnosis were calculated for 24,900 TCS (median age, TC diagnosis: 33 y) reported to population-based cancer registries in the NCI SEER program (1973-2014). TCS were initially given CHEM (n=6,340), RT (n=9,058), or SURG (n=8,995), with each group accruing 80,700, 156,735, and 128,039 person-years (PY) of follow-up, respectively. Results: During 372,709 PY of follow-up, 1,625 TCS developed SMN and 228 developed HMN, including 107 lymphomas, 92 leukemias, and 29 plasma cell dyscrasias. Among all TCS, overall risk of SMN was increased by 1.06-fold (95% CI 1.01-1.1). Risks of SMN were increased after RT (SIR 1.1, 95% CI 1.06-1.2) and CHEM (SIR 1.3, 95% CI 1.1-1.4); but not after SURG (SIR 0.8). After CHEM, significant excesses of SMN of the pancreas (SIR 2.2), soft tissue (SIR 4.0), kidney (SIR 1.7), thyroid (SIR 3.3) occurred; after RT, significantly elevated risks for SMN of the stomach (SIR 1.7), rectum/sigmoid (SIR 1.4), pancreas (SIR 2.7), soft tissue (SIR 2.2), bladder (SIR 1.5), and thyroid (SIR 2.0) were observed. The 30 year cumulative incidence of SMN after SURG, CHEM, and RT was 8.9% (95% CI 7.8-9.9), 10.1% (95% CI 8.8-11.5) and 17.0% (95% CI 15.8-18.2), respectively. Significantly increased risks of leukemia followed CHEM (SIR 2.7) and SURG (SIR 1.8) and were driven by increased risks for acute myeloid leukemia, with significant excesses restricted to 1-10 y and 1-5 y after TC diagnosis, respectively; nonsignificant 2-fold excesses occurred 1-10 y after RT. Risks for lymphoma and plasma cell dyscrasias were not elevated (1.02 and 1.27, respectively). Conclusions: In the largest population-based study of U.S. TCS to date, we report significant 6% excesses of SMN and 2-fold increased risks of leukemias. Efforts to minimize CHEM exposure and decrease doses/field size of RT in TC should continue. TCS should be educated about cancer prevention and screening.
Preemptive versus reactive topical clobetasol for regorafenib-induced hand-foot reactions: Results from the ReDOS trial.
Authors: Jatoi Aminah , Ou Fang-Shu , Ahn Daniel H. , Boland Patrick McKay , Ciombor Kristen Keon , Jacobs Nisha Lassi , Pasche Boris , Cleary James M. , McCune Jeannine S. , Pedersen Katrina , Barzi Afsaneh , Chiorean E. Gabriela , Heying Erica N. , Lenz Heinz-Josef , Sloan Jeff A. , Lacouture Mario E. , Grothey Axel , Bekaii-Saab Tanios S.
Published: March 2020

11586

Background: Hand-foot skin reaction (HFSR) is the most common regorafenib adverse event. However, no intervention has demonstrated efficacy in preventing or palliating this adverse event, short of modulating the regorafenib dose. Methods: The Regorafenib Dose Optimization Study (ReDOS) was a randomized trial ( https://clinicaltrials.gov/ct2/show/NCT02368886 ); here we describe an a priori secondary analysis of ReDOS with the goal of assessing whether clobetasol 0.05% cream (a potent corticosteroid) applied to the palms and soles twice per day is more effective when prescribed pre-emptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the 1st 2 cycles of regorafenib. Results: Among 116 evaluable patients, 61 received pre-emptive clobetasol, and 55 reactive clobetasol. Baseline demographics were comparable between groups. During the 1st regorafenib cycle, 46% and 52% of patients developed HFSR with pre-emptive and reactive clobetasol, respectively (p = 0.52). However, during the 2nd cycle, 56% (of 47 total patients) and 80% (of 41 total patients), developed this toxicity with pre-emptive and reactive clobetasol, respectively (p = 0.02). Of note, during the 2nd cycle, rates of grade 1,2, and 3 HFSR were 40%, 11%, and 4% (pre-emptive) and 45%, 25%, and 10% (reactive) (p = 0.07). A sensitivity analysis to examine rates of no HFSR over all 2 regorafenib cycles showed that no HFSR occurred in 33% (of 61 total patients) with pre-emptive clobetasol versus 15% (of 55 total patients) with reactive clobetasol (p = 0.02). Patient-reported outcomes showed HFSR compromised activities of daily living, including getting dressed, preparing meals, walking, and even driving, with seemingly worse descriptive outcomes in patients who received reactive therapy. No adverse events from clobetasol were reported. Conclusions: Compared to reactive therapy, pre-emptive topical clobetasol might lessen regorafenib-induced HFSR. Clinical trial information: NCT02368886.
Response to A+CHP by CD30 expression in the ECHELON-2 trial.
Authors: Advani Ranjana H. , Horwitz Steven M. , Iyer Swaminathan Padmanabhan , Bartlett Nancy L. , Kim Won Seog , Tilly Herve , Belada David , Feldman Tatyana , Illés Árpád , Jacobsen Eric D. , Huettmann Andreas , Zinzani Pier Luigi , O'Connor Owen A. , Trepicchio William L. , Miao Harry H. , Rao Shangbang , Onsum Matthew , Manley Thomas John , Illidge Tim
Published: March 2020

7538

Background: Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30. The ECHELON-2 (E-2) study demonstrated significantly longer progression-free and overall survival with BV plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP in frontline treatment of patients (pts) with CD30+ peripheral T-cell lymphoma (PTCL). Complete remission (CR) rate (A+CHP 68%; CHOP 56%) and objective response rate (ORR) (A+CHP 83%; CHOP 72%) were also significantly increased. Expression of CD30 is universal in systemic anaplastic large-cell lymphoma (sALCL) but variable among non-sALCL subtypes. As ORR is a direct measure of antitumor activity, we examined response to A+CHP by CD30 expression. Methods: Pts with CD30+ (≥10% by local review) PTCL were included in E-2. Eligible histologies included ALK+ sALCL (IPI ≥2), ALK− sALCL, PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukemia/lymphoma, enteropathy-associated T-cell lymphoma, and hepatosplenic T-cell lymphoma. We analyzed the relationship between CD30 expression (IHC Ber H2 antibody) above and below the median (median CD30=18% PTCL-NOS; 25% AITL) and CR rate, ORR, and duration of CR (DOCR) in pts with AITL and PTCL-NOS treated with A+CHP. Results: Most (26/29, 90%) AITL pts had CD30 expression between 10% and 30%. PTCL-NOS pts were more evenly distributed across levels of CD30 expression ranging from 10% to 100%. CD30 levels were neither predictive of response (Table) nor significantly associated with DOCR in pts with AITL (P=0.30) or PTCL-NOS (P=0.90) (log-rank test). Response by CD30 expression. Clinical trial information: NCT01777152. Conclusions: CD30 expression above vs below median (or at 10%) did not predict response to A+CHP in E-2 non-ALCL subtypes, as responses were seen across CD30 levels. This may be due to intra- and inter-tumoral heterogeneity of CD30 expression, limitations of IHC, the nature of CD30 on the cell surface, and multiple mechanisms of action of BV. Further evaluation of the expression-response relationship in PTCL pts with CD30 <10% is warranted.[Table: see text]
Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Interim analysis and biomarker data from a multicenter study (LCMC3).
Authors: Kwiatkowski David J. , Rusch Valerie W. , Chaft Jamie E. , Johnson Bruce E. , Nicholas Alan , Wistuba Ignacio Ivan , Merritt Robert , Lee Jay M. , Bunn Paul A. , Tang Yan , Phan See-Chun , Waqar Saiama Naheed , Patterson Alexander , Haura Eric B. , Toloza Eric M. , Reckamp Karen L. , Raz Dan , Schulze Katja , Johnson Ann , Carbone David Paul
Published: March 2020

8503

Background: Small pilot studies (e.g., N Engl J Med. 2018;378:1976) have shown that preoperative immune checkpoint inhibitor therapy may be of benefit in early-stage NSCLC. This large multicenter trial assesses the benefit of neoadjuvant treatment with atezolizumab (atezo; NCT02927301). Methods: Patients (pts) with stages IB to selected IIIB resectable NSCLC receive 2 cycles of atezo 1200 mg (days 1, 22) then undergo resection (day 40 ± 10). Primary tumor +/- node biopsies and blood samples are obtained before atezo and at surgery for biomarker studies. The primary endpoint is major pathological response (MPR), defined as ≤ 10% viable tumor cells in the resection specimen. Secondary endpoints include safety and correlation of response with PD-L1 expression, tumor mutation burden (TMB) and gene expression signatures. Results: For this interim efficacy analysis (5 Sep 2018 data cut), we report on the first 101 of 180 planned pts: 47 males, median age, 64 y; all ECOG PS 0-1; 23 current and 68 former smokers; 66 non-squamous NSCLC; clinical stages IB/IIA/IIB/IIIA/IIIB n = 11/16/28/39/7. There were 2 treatment-unrelated Gr 5 AEs (cardiac death post surgical resection; death due to disease progression), 29 Gr 3-4 AEs (6 [6%] treatment related). 90 pts had surgery. Excluding 8 pts who had driver mutations (7 EGFR, 1 ALK, no MPR), MPR rate was 15/82 (18%, 95% CI 11%-28%), 4 pts had pathological complete response (pCR). By RECIST, 6/82 pts had PR, 72 had SD and 4 had PD. Two of 26 (8%) PD-L1− (TC0 and IC0, clone SP142) and 10 of 35 (29%) PD-L1+ had MPR ( P= 0.055). Five of 44 (11%) TPS < 50 (PD-L1 clone 22C3) and 7 of 20 (35%) TPS > 50 had MPR ( P= 0.040). Exome sequencing data was available for 47/101 pts. Median TMB was 10.4 (range, 1.5-46.5) mutations per Mb and was not different in those with MPR compared with those without MPR. Further analysis of TMB, mutation signatures, and gene expression profiling is ongoing. Conclusions: Atezo in the neoadjuvant setting was well tolerated, and pCR and MPR rates are encouraging in this large multicenter trial. Efficacy interim analysis passed its futility boundary, and study enrollment continues. Safety, efficacy results and ongoing correlative analyses will be presented. Clinical trial information: NCT02927301.
Real-world experience and molecular features of response to immune checkpoint blockade in patients with recurrent small cell lung cancer.
Authors: Lai Wei-Chu Victoria , Rizvi Hira , Egger Jacklynn V. , Plodkowski Andrew J. , Ginsberg Michelle S. , Kris Mark G. , Beras Amanda , Rekhtman Natasha , Poirier John T. , Hellmann Matthew David , Rudin Charles M.
Published: March 2020

8556

Background: Immune checkpoint blockade (ICB) is now a routine component of treatment in recurrent small cell lung cancer (SCLC). We evaluated the response to ICB in patients (pts) with recurrent SCLC and genomic features of response using next-generation sequencing (NGS). Methods: Pts with recurrent SCLC treated with ICB were identified. The majority of pts were treated outside of a clinical trial to focus emphasis on the real-world experience. Tumor mutation burden (TMB) and the landscape of somatic variants were determined by targeted NGS using MSK-IMPACT. Objective response rate (ORR) to ICB was determined using RECIST v1.1. PFS and OS were measured from the start of ICB and analyzed using Kaplan-Meier. Results: Between December 2013 and October 2018, 108 pts with SCLC were treated with ICB (57 subjected to NGS). Pts received PD-1 monotherapy alone (n = 28) or in combination with CTLA-4 blockade (n = 80). Median line of therapy was 2 (range 1-6). ORR was 14% (15/108, 95% CI 8-22%). From the start of ICB, median PFS was 1.4 months in non-responders and 10.8 months in responders (HR 0.2; 95% CI 0.13-0.32). Median OS was 6.3 months in non-responders and undefined in responders (range 8-44 months) (HR 0.26, 95% CI 0.16-0.44). Four responders remain on ICB treatment. TMB in the ICB-treated cohort was similar to that of an unselected cohort (n = 233) of SCLC (median 8.8 Mt/MB vs 8.2 Mt/MB, p = 0.71). Clinical benefit was enriched among those with a higher TMB (upper vs middle/lower tertile PFS HR 0.48, 95% CI 0.28-0.84, p = 0.01 and ORR 26% [5/19] vs ORR 8% [3/38]). Rates of whole genome duplication and commonly altered genes in SCLC ( TP53, RB1, KMT2C/D, NOTCH1/2/4, PTPRD, APC) were similarly distributed across responders and non-responders. Completion of whole-exome sequencing and PD-L1 testing is in progress. Conclusions: In pts with recurrent SCLC receiving routine clinical care, the ORR to ICB is comparable to reports from clinical trials. A high TMB was associated with a longer median PFS and better response. Further investigation into the genomic landscape of recurrent SCLC is needed to identify biomarkers predictive of response to ICB.
Using MALDI-TOF mass spectrometry for tracking of minimal residual disease in peripheral blood from patients with multiple myeloma.
Authors: Eveillard Marion , Rustad Even , Roshal Mikhail , Zhang Yanming , Ciardiello Amanda , Korde Neha , Hultcrantz Malin , Hassoun Hani , Smith Eric L. , Lesokhin Alexander M. , Mailankody Sham , Landgren Carl Ola , Thoren Katie
Published: March 2020

e19525

Background: Minimal residual disease (MRD) negativity after completed therapy is associated with longer progression-free survival (PFS) in patients with multiple myeloma (MM). Current standard of care for MRD testing use flow cytometry and/or next generation sequencing (NGS)-based assays applied on bone marrow (BM) aspirate samples. To develop a strategy for MRD tracking in peripheral blood (PB), we were motivated to evaluate MALDI-TOF head-to-head with established bone marrow-based MRD assays. Methods: We used MALDI-TOF mass spectrometry to detect M-proteins in PB. Our cohort included patients who had serum samples available at 2 timepoints including during active disease and within 60 days of MRD results as determined by flow cytometry of BM aspirates. The cohort enrolled 71 patients (26 females, 45 males) with a median age of 61 years (37-78 years). Twenty-seven patients had high-risk cytogenetics at baseline. Patients were classified at diagnosis as ISS1 (n = 38), ISS2 (n = 18) or ISS3 (n = 6). The flow cytometry based MRD assay was performed using MSKCCs 10-color, single-tube method. MALDI-TOF analysis was performed as described by Mills et al. Samples taken during active disease were used to identify the mass/charge ratio of the M-protein at baseline and in follow-up samples. MALDI-TOF results were compared to flow cytometry bone marrow-based MRD results. Results: The median time between diagnosis and the MRD timepoint was 13.4 months (3.4-91 months). MALDI-TOF in PB and flow cytometry BM-based MRD results were concordant for 44/71 (62%) patients (8+/+, 36 -/- respectively) while 27 were discordant (10 +/-, 17-/+). Fifty-four of 71 patients were in complete response (CR) (45/54 in sCR) at the time of MRD. MALDI-TOF was still positive in 13 of these 54 CR patients. In this cohort, the median PFS since MRD assessment was not reached in the 2 subgroups of double negative patients (n = 31) or in patients with a positive result in at least one technique (n = 23) with a median follow-up of 11.2 months (0-34.6 months). Conclusions: In 44/71 (62%) samples, MALDI-TOF of PB results and flow cytometry BM-based MRD results were concordant. MALDI-TOF of PB may be useful for detecting measurable residual disease and for the monitoring of MM patients during maintenance therapy with the future goal to rule out early recurrent disease.
Inflammation Triggered by Saturated Fat Ingestion Is Linked to Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome
Authors: González Frank , Considine Robert V , Abdelhadi Ola A , Acton Anthony J
Published: March 2020

Context

Inflammation and insulin resistance are often present in polycystic ovary syndrome (PCOS).

Objective

We determined the effect of saturated fat ingestion on mononuclear cell (MNC) nuclear factor-κB (NFκB) activation; NFκB, inhibitory-κBα (IκBα), and tumor necrosis factor-α (TNFα) gene expression; and circulating C-reactive protein (CRP) in women with PCOS.

Design

Cross-sectional study.

Setting

Academic medical center.

Patients

Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity).

Main Outcome Measures

Activated NFκB, NFκB heterodimer subunits, IκBα and TNFα messenger ribonucleic acid content and NFκB p65 and IκBα protein content were quantified in mononuclear cells (MNC), and CRP was measured in plasma from blood drawn fasting and 2, 3, and 5 h after saturated fat ingestion. Insulin sensitivity was derived from oral glucose tolerance testing (ISOGTT). Androgen secretion was assessed from blood drawn fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration.

Results

In response to saturated fat ingestion, women with PCOS regardless of weight class exhibited lipid-induced increases in activated NFκB, NFκB, and TNFα gene expression and plasma CRP and decreases in IκBα protein compared with lean control subjects. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. Lipid-stimulated NFκB activation was negatively correlated with ISOGTT, and positively correlated with HCG-stimulated androgen secretion.

Conclusion

In PCOS, increases in NFκB activation and circulating CRP and decreases in IκBα protein following saturated fat ingestion are independent of obesity. Circulating MNC and excess adipose tissue are separate and distinct contributors to inflammation in this disorder.
A Gatekeeping Role of ESR2 to Maintain the Primordial Follicle Reserve
Authors: Chakravarthi V Praveen , Ghosh Subhra , Roby Katherine F , Wolfe Michael W , Rumi M A Karim
Published: March 2020

Over the entire reproductive lifespan in mammals, a fixed number of primordial follicles serve as the source of mature oocytes. Uncontrolled and excessive activation of primordial follicles can lead to depletion of the ovarian reserve. We observed that disruption of estrogen receptor β (ESR2) signaling results in increased activation of primordial follicles in Esr2-null (Esr2–/–) rats. However, follicle assembly was unaffected, and the total number of follicles remained comparable between neonatal wild-type and Esr2–/– ovaries. While the activated follicle counts were increased in Esr2–/– ovary, the number of primordial follicles were markedly decreased. Excessive recruitment of primordial follicles led to premature ovarian senescence in Esr2–/– rats and was associated with reduced levels of serum AMH and estradiol. Disruption of ESR2 signaling through administration of a selective antagonist (PHTPP) increased the number of activated follicles in wildtype rats, whereas a selective agonist (DPN) decreased follicle activation. In contrast, primordial follicle activation was not increased in the absence of ESR1, indicating that the regulation of primordial follicle activation is ESR2 specific. Follicle activation was also increased in Esr2 mutants lacking the DNA binding domain, suggesting a role for the canonical transcriptional activation function. Both primordial and activated follicles express ESR2, suggesting a direct regulatory role for ESR2 within these follicles. We also detected that loss of ESR2 augmented the activation of AKT, ERK, and mTOR pathways. Our results indicate that the lack of ESR2 upregulated both granulosa and oocyte factors, which can facilitate AKT and mTOR activation in Esr2–/– ovaries leading to increased activation of primordial follicles.
Essential Role of Syntaxin-Binding Protein-1 in the Regulation of Glucagon-Like Peptide-1 Secretion
Authors: Campbell Jhenielle R , Martchenko Alexandre , Sweeney Maegan E , Maalouf Michael F , Psichas Arianna , Gribble Fiona M , Reimann Frank , Brubaker Patricia L
Published: March 2020

Circadian secretion of the incretin, glucagon-like peptide-1 (GLP-1), correlates with expression of the core clock gene, Bmal1, in the intestinal L-cell. Several SNARE proteins known to be circadian in pancreatic α- and β-cells are also necessary for GLP-1 secretion. However, the role of the accessory SNARE, Syntaxin binding protein-1 (Stxbp1; also known as Munc18-1) in the L-cell is unknown. The aim of this study was to determine whether Stxbp1 is under circadian regulation in the L-cell and its role in the control of GLP-1 secretion. Stxbp1 was highly-enriched in L-cells, and STXBP1 was expressed in a subpopulation of L-cells in mouse and human intestinal sections. Stxbp1 transcripts and protein displayed circadian patterns in mGLUTag L-cells line, while chromatin-immunoprecipitation revealed increased interaction between BMAL1 and Stxbp1 at the peak time-point of the circadian pattern. STXBP1 recruitment to the cytosol and plasma membrane within 30 minutes of L-cell stimulation was also observed at this time-point. Loss of Stxbp1 in vitro and in vivo led to reduced stimulated GLP-1 secretion at the peak time-point of circadian release, and impaired GLP-1 secretion ex vivo. In conclusion, Stxbp1 is a circadian regulated exocytotic protein in the intestinal L-cell that is an essential regulatory component of GLP-1 secretion.
The lymph node at a glance – how spatial organization optimizes the immune response
Authors: Grant Spencer M. , Lou Meng , Yao Li , Germain Ronald N. , Radtke Andrea J.
Published: March 2020

A hallmark of the mammalian immune system is its ability to respond efficiently to foreign antigens without eliciting an inappropriate response to self-antigens. Furthermore, a robust immune response requires the coordination of a diverse range of cells present at low frequencies within the host. This problem is solved, in part, by concentrating antigens, antigen-presenting cells and antigen-responsive cells in lymph nodes (LNs). Beyond housing these cell types in one location, LNs are highly organized structures consisting of pre-positioned cells within well-defined microanatomical niches. In this Cell Science at a Glance article and accompanying poster, we outline the key cellular populations and components of the LN microenvironment that are present at steady state and chronicle the dynamic changes in these elements following an immune response. This review highlights the LN as a staging ground for both innate and adaptive immune responses, while providing an elegant example of how structure informs function.
Paraneoplastic Diseases of the Central Nervous System
Authors: Galli Jonathan , Greenlee John
Published: March 2020

Paraneoplastic neurological syndromes are nonmetastatic complications of malignancy secondary to immune-mediated neuronal dysfunction or death. Pathogenesis may occur from cell surface binding of antineuronal antibodies leading to dysfunction of the target protein, or from antibodies binding against intracellular antigens which ultimately leads to cell death. There are several classical neurological paraneoplastic phenotypes including subacute cerebellar degeneration, limbic encephalitis, encephalomyelitis, and dorsal sensory neuropathy. The patient’s clinical presentations may be suggestive to the treating clinician as to the specific underlying paraneoplastic antibody. Specific antibodies often correlate with the specific underlying tumor type, and malignancy screening is essential in all patients with paraneoplastic neurological disease. Prompt initiation of immunotherapy is essential in the treatment of patients with paraneoplastic neurological disease, often more effective in cell surface antibodies in comparison to intracellular antibodies, as is removal of the underlying tumor.
Benefit of cinnamon (Cinnamomum burmannii) in lowering total cholesterol level after consumption of high-fat containing foods in white mice (Mus musculus) models
Authors: Pulungan Annisa , Pane Yunita Sari
Published: March 2020

Background: Hypercholesterolemia is a condition where cholesterol levels in the body exceed the normal range. In Indonesia, the development of traditional medicine is carried out by examining plants known for their medicinal qualities, including cinnamon (Cinnamomum burmannii). There are many nutritional components contained in cinnamon, such as cinnamaldehyde. This has been suggested as a substance that can reduce cholesterol and triglyceride levels. This study was conducted to determine the efficacy of cinnamon in reducing total cholesterol levels of mice (Mus musculus) given high-fat feed.

Methods: This is an experimental study with a pre-post control study design. The groupings were performed by a simple random sampling method. There were five groups (n=6/group): 1) Negative control (aquadest); 2) positive control of high-fat containing food (HFC; quail's yolk); 3) HFC + cinnamon extract (CE; dose 2mg/20g body weight (BW); 4) HFC + CE (dose 4mg/20gBW); 5) HFC + CE (dose 8mg/20gBW). The study was conducted for 28 days. The intervention of CE started on day 15 and ended on day 28. Measurement of total cholesterol and BW of mice was performed on days 0, 14 and 28.

Results: A decrease in the total cholesterol of mice (p = 0.001) was found in the groups that consumed CE. However, there was not a significant change between groups in mice BW (p = 0.419).

Conclusions: Providing cinnamon extract (Cinnamomum burmannii) for 28 days could decrease total cholesterol levels in mice compared to those not given cinnamon extract when consuming high-fat containing foods.
Co-creation in music and music education
Authors: Kuprina Elena
Published: March 2020

The monograph is devoted to the problem of musical co-creation, represents the artistic and dynamic system. The author considers the musical co-creation from the perspective of interdisciplinary approach, as the phase of the creative process, featuring self-contained characteristics, manifested in the "I" and "I'm Different" through specific regularities and principles.
In music co-creation differentiated into spheres, types and forms, where the role of the ratio of the subjects and the performance of co-creative artistic projects are analyzed from the position of system dynamics. In music education operates a pedagogy of co-creation, manifesting the specifics through professional, psychological, reflective, and educational facets. Presented to the organizational form of the pedagogy of co-creation, from the perspective of information approach given the findings of a study of the influence of pop on the sensory system of the student of a musician-performer (the performer).
Can be used in courses of the disciplines of the history of music, music psychology and music pedagogy, pedagogy of co-creation. Addressed to students of music schools, teachers, musicians of all disciplines, musicologists and cultural studies, researchers, creative processes, and a wide circle of curious readers.
Structure and function of the Central Bank of the Russian Federation
Authors: Kazimagomedov Abdulla
Published: March 2020

The textbook covers the basic issues related to the activities of the Central Bank of the Russian Federation. A short and accessible educational material presented on organizational bases of activities, operations and functions of the Central Bank of the Russian Federation. Additionally, to consolidate the knowledge the students are given control questions and tests.
Meets the requirements of Federal state educational standard of secondary professional education in the specialty 38.02.07 "Banking", approved by order of Ministry of education of Russia from 28.07.2014 No. 837.
For students and teachers, and anyone interested in issues related to the activities of the Central Bank of the Russian Federation.
Ownership Change and Firm Innovation: The Mediating Role of Interest Alignment
Authors: He Wenlong , He Zi-Lin , Tong Tony W.
Published: March 2020

Although many studies suggest a strong link between ownership and corporate strategy, little research has examined how ownership change matters for firm innovation. This paper leverages the context of privatization to study how firms’ transition from state ownership to private ownership shapes innovation. We argue that privatization helps to alleviate not only traditional principal–agent conflicts, but also principal–principal conflicts in firms of concentrated ownership, leading to greater innovation. Exploiting a major privatization reform in China, we show that privatization enhances firm innovation and that this effect is mediated by interest alignment between firm owners and managers as well as that between controlling and minority shareholders. This study contributes to a dynamic view of ownership and innovation by delineating the underlying mechanisms through which privatization affects innovation.
Lightweight Messaging for Efficient Service Discovery in Mobile IoT Environments Using Hierarchical Bloom Filters
Authors: Kim Minhyeop , Kwon Jung-Hyun , Jo Hyeon-Jun , Ko In-Young
Published: March 2020

In highly dynamic IoT environments, the connection statuses of IoT resources and the availability of IoT-based services change frequently. Therefore, to successfully build distributed service registries for managing and finding the information about available services in an effective manner, it is crucial to minimize the overhead of message exchanges between registries and to reduce the time overhead for identifying the capabilities of available IoT resources and the services that can be provided by utilizing these capabilities. In this paper, we propose a lightweight messaging approach that uses hierarchical Bloom filters to efficiently represent service information to be exchanged and managed by distributed service registries for IoT environments with high mobility. We also propose a method for serializing the dimensions of a Bloom-filter-encoded search space. We conducted experiments to demonstrate the improvement in the service discovery performance, the reduction in message traffic among service registries, and the decrease in the latency when synchronizing distributed service registries.
The ‘Dubrovnik Manifesto’
Authors: Lavalette Michael
Published: March 2020

As Editor-in-Chief of CRSW, I am delighted that we have been offered the chance to publish the ‘Dubrovnik Manifesto’. The manifesto is the outcome of a collaborative process, written collectively by participants at the Dubrovnik social work conference in 2019. I would like to record our thanks for their permission to reproduce it here.
Dual-polarized highly sensitive surface-plasmon-resonance-based chemical and biomolecular sensor
Authors: Rakibul Islam Mohammad , Iftekher A. N. M. , Rakibul Hasan Kazi , Nayen Md. Julkar , Bin Islam Saimon
Published: March 2020

As the research work in surface plasmon resonance (SPR)-based photonic crystal fiber (PCF) is getting tighter, a perfectly circular-shaped PCF with elliptical air holes is proposed where the performance parameters are improved significantly. The performances among our designed elliptical, circular, and rectangular air holes are compared, and the best result is achieved with the elliptical air holes. The technique used for the investigation is the finite element method, and for the simulation of data COMSOL Multiphysics 5.3a software is used. The method covers a wider range of the optical spectrum from 0.59 to 1.05 µm. The highest confinement loss achieved through our design is 340 dB/cm. The wavelength sensitivity and amplitude sensitivity are 13,000 nm/RIU and

1189.46

R
I
U

−
1

, respectively. The sensor resolution is

7.69

×

10

−
6

for our proposed design. The proposed sensor also achieved a maximum birefringence of

2.8

×

10

−
3

, which is, to our knowledge, the highest birefringence reported so far for a PCF-SPR sensor. This enables the fiber to be operated in a dual-polarized mode. The RI for the analyte ranges from 1.33 to 1.40. Based on all the characteristics, the proposed PCF structure can be used effectively for chemical and biomolecular sensing.
Multifocal microlens arrays using multilayer photolithography
Authors: Bae Sang-In , Kim Kisoo , Yang Sungpyo , Jang Kyung-won , Jeong Ki-Hun
Published: March 2020

We report a new microfabrication method of multifocal microlens arrays (MF-MLAs) for extended depth-of-field (DoF) using multilayer photolithography and thermal reflow. Microlenses of different focal lengths were simultaneously fabricated on a single glass wafer by using repeated photolithography with multiple photomasks to define microposts of different thicknesses and concurrent thermal reflow of multi-stacked microposts. The diverse lens curvatures of MF-MLAs are precisely controlled by the thickness of the micropost. Hexagonally packaged MF-MLAs clearly show three different focal lengths of 249 µm, 310 µm, and 460 µm for 200 µm in lens diameter and result in multifocal images on a single image sensor. This method provides a new route for developing various three-dimensional (3D) imaging applications such as light-field cameras or 3D medical endoscopes.
Telemetry-Driven Optical 5G Serverless Architecture for Latency-Sensitive Edge Computing
Authors: Pelle István , Paolucci Francesco , Sonkoly Balázs , Cugini Filippo
Published: March 2020

Latency-sensitive serverless subfunctions are optimally deployed at edge and cloud according to telemetry-retrieved data from the 5G transport infrastructure. Once deployed, serverless functions provided extremely fast invocation time of less than 450ms.
Multi-stage Aggregation and Lightpath Provisioning of Geo-distributed Data over EON Assisted by MEC
Authors: Liu Zhen , Zhang Jiawei , Guo Zizheng , Ji Yuefeng
Published: March 2020

A multi-stage aggregation and lightpath provisioning algorithm is proposed for geo-distributed data in EON assisted by MEC. Simulation results show the algorithm can reduce the job completion time and bandwidth consumption.
Dynamically Controlled Flexible-Grid Networks Based on Semi-Flexible Spectrum Assignment and Network-State-Value Evaluation
Authors: Shiraki Ryuta , Mori Yojiro , Hasegawa Hiroshi , Sato Ken-ichi
Published: March 2020

We propose a novel RSA algorithm for dynamically-changing flexible-grid networks. The proposed scheme can suppress spectral fragmentation and adapt to traffic-distribution change. Extensive simulations show that the fiber-utilization efficiency is increased by 1% to 57%.
Quasi-coherent Technology for Cost Efficient High Loss Budget Transmission
Authors: Jensen Jesper Bevensee , Altabas Jose. A , Gallardo Omar , Squartecchia Michele , Valdecasa Guillermo Silva
Published: March 2020

In this paper, we present results achieved with real-time quasi-coherent receivers in context with challenges for next generation access networks. −35 dBm receiver sensitivity at 10 Gbps for NG-PON2 applications and 32.5 km 25 Gbps C-band transmission over an uncompensated SSMF link for 5G front/mid-haul is presented.
PAM-X™: A 25Gb/s-PAM4 Optical Transceiver Chipset for 5G Optical Front-Haul
Authors: Wang Xin , Peng Yi , Zhang Yuanxi , Xia Tao , Wu Yifan , Wang Juncheng , Wang Lei , Song Liujia , Zhao Lei , Zhuo Shenglong , Pan Quan , Chen Xuefeng , Chiang Patrick Yin , Bai Rui
Published: March 2020

A complete 25Gb/s PAM4 optical transceiver chipset using commercial 10G-lasers for 10km single-mode fiber is presented. Measurement results demonstrate <−12dBm sensitivity across all temperatures and <30pJ/bit power efficiency.
Deep Learning Based Digital Back Propagation with Polarization State Rotation & Phase Noise Invariance
Authors: Bitachon Bertold Ian , Ghazisaeidi Amirhossein , Baeuerle Benedikt , Eppenberger Marco , Leuthold Juerg
Published: March 2020

A new deep learning training method for digital back propagation (DBP) is introduced. It is invariant to polarization state rotation and phase noise. Applying the method one gains more than 1 dB over standard DBP.
High speed 2D-PDA FSO receiver for high optical alignment robustness with space diversity
Authors: Umezawa Toshimasa , Yoshida Yuki , Kanno Atsushi , Yamamoto Naokatsu , Kawanishi Tetsuya
Published: March 2020

We present a free space optics receiver with high robustness for optical alignment using a large active area, high-speed 2D-PDA, and its demonstration of 40-Gbps (PAM4) signal detection using a space diversity technique in DSP.
Beyond 100-kbit/s Transmission over Rolling Shutter Camera-based VLC Enabled by Color and Spatial Multiplexing
Authors: Liu Liqiong , Deng Rui , Shi Jin , He Jing , Chen Lian-Kuan
Published: March 2020

The camera-based VLC (CVLC) is a promising technique for various application scenarios. For the first time, we demonstrate a rolling shutter based CVLC system with beyond 100-kbit/s data rate by employing color and spatial multiplexing.
Capacity sharing approaches in multi-tenant, multi-service PONs for low-latency fronthaul applications based on cooperative-DBA
Authors: Ahmad Arsalan , Slyne Frank , Zeb Sanwal , Wahab Abdul , Khan Rana Azhar , Ruffini Marco
Published: March 2020

We propose and compare algorithms to allocate upstream PON capacity, where multiple virtual operators generate independent frame-level allocation over shared infrastructure. Our fragmentation-based approach shows the ability to limit latency increase to a few microseconds.
4×112 Gbps/fiber CWDM VCSEL Arrays for Co-Packaged Interconnects
Authors: Wang Binhao , Sorin Wayne V. , Rosenberg Paul , Kiyama Lennie , Mathai Sagi , Tan Michael R.T.
Published: March 2020

We demonstrate a 4×112 Gbps/fiber VCSEL link using a co-packaged coarse wavelength division multiplexing (CWDM) optical module. A complete co-packaged CWDM module can achieve a 2.668 Tb/s aggregated bandwidth by assembling four 1×6 VCSEL arrays.
Bandwidth Enhancement of Directly Modulated Lasers Butt-coupled with Silica-Based AWG by External Optical Feedback Effect
Authors: Yun Seok-Jun , Han Young-Tak , Kim Seok-Tae , Shin Jang-Uk , Park Sang-Ho , Lee Dong-Hoon , Lee Seo-Young , Baek Yongsoon
Published: March 2020

By external optical feedback effect on DMLs butt-coupled with a silica-based AWG, we present that 3-dB bandwidths of a DML submodule can be extended to ~37.5 GHz (@ 90 mA) using commercial 28-Gbaud DML chips.
O-band Reflective Electroabsorption Modulator for 50 Gb/s NRZ and PAM-4 Colorless Transmission
Authors: Atra Kebede , Cerulo Giancarlo , Provost Jean-Guy , Jorge Filipe , Blache Fabrice , Mekhazni Karim , Garreau Alexandre , Pommereau Frederic , Gomez Carmen , Fortin Catherine , Ware Cedric , Erasme Didier , Mallecot Franck , Achouche Mohand
Published: March 2020

we present a 50 Gb/s O-band reflective electroabsorption modulator operating in both non-return-to-zero (NRZ) and PAM-4 modulation formats without equalization. We obtained >9 dB NRZ dynamic extinction ratio for a peak-to-peak voltage of 2.4 V.
Single-pixel imaging through multimode fiber using silicon optical phased array chip
Authors: Fukui Taichiro , Kohno Yusuke , Tang Rui , Nakano Yoshiaki , Tanemura Takuo
Published: March 2020

We experimentally demonstrate single-pixel imaging using a multimode fiber attached with optical phased-array chip. By driving 128 integrated phase shifters, speckle patterns are generated from the fiber to realize clear imaging with 490 resolvable points.
Field and Laboratory Demonstration of 48nm Optical Transport with Real-Time 32T (80×400G) over G.652 Fiber Distances up to 640km
Authors: Kumar Praveen , Sanghi Deepak , Chatterjee Sumit , Pan Deng , Tang Xuefeng , Zhang Zhuhong , Li Chuandong , Jian Deng , Zhang Dejiang
Published: March 2020

We report first successful field trial and laboratory demonstration of 48nm extended C band transport. Error-free transmission of 32Tb/s (80×400Gb/s) is achieved over 640km G.652 link in laboratory and 42km G.652 link in field.
<500ns Latency Overhead Analog-to-digital-compression Radio-over-fiber (ADX-RoF) Transport of 16-channel MIMO, 1024QAM Signals with 5G NR Bandwidth
Authors: Zhu Paikun , Yoshida Yuki , Kitayama Ken-ichi
Published: March 2020

Real-time analog-to-digital-compression radio-over-fiber (ADX-RoF) transport with <500ns processing latency overhead is demonstrated by using a single-chip programmable radio platform. 16-channel 61.44MHz 1024QAM-OFDM signals of 5G NR-class is delivered with ~4-Gb/s optical OOK interface, maintaining EVM<1.4%.
Design Strategies Exploiting C+L-band in Networks with Geographically-dependent Fiber Upgrade Expenditures
Authors: Moniz Daniela , Lopez Victor , Pedro João
Published: March 2020

This paper proposes a framework leveraging next-generation interfaces and C+L-band to design transport networks where fiber-based capacity upgrade is geographically-dependent. Simulation results highlight the effectiveness of the proposal and the possible trade-offs between number of line interfaces and fibers.
PON Virtualisation with EAST-WEST Communications for Low-Latency Converged Multi-Access Edge Computing (MEC)
Authors: Das Sandip , Ruffini Marco
Published: March 2020

We propose a virtual-PON based Mobile Fronthaul (MFH) architecture that allows direct communications between edge points (enabling EAST-WEST communication). Dynamic slicing improves service multiplexing while supporting ultra-low latency under 100µs between cells and MEC nodes.
Asynchronous Multi-Service Fiber-Wireless Integrated Network Using UFMC and PS for Flexible 5G Applications
Authors: Chen You-Wei , Zhang Rui , Su Shang-Jen , Shen Shuyi , Zhou Qi , Yao Shuang , Chang Gee-Kung
Published: March 2020

A multi-service fiber-wireless integrated network is experimentally demonstrated using both UFMC and PS. Asynchronous transmission with suppressed inter-service interference and optimized information rate is verified through a 25-km fiber and a 5-m 60-GHz wireless link.
Gigabit/s Optical Wireless Access and Indoor Networks
Authors: Nirmalathas Thas Ampalavanapillai , Song Tingting , Edirisinghe Sampath , Tian Liang , Lim Christina , Wong Elaine , Wang Ke , Ranaweera Chathurika , Alameh Kamal
Published: March 2020

Optical wireless networks are being explored as a wireless alternative for provision of multi gigabits/second wireless and this paper presents an overview of recent progress and outstanding challenges. and technologies.
All-Optical Spectral Magnification of WDM Signals after 50 km of Dispersion Un-Compensated Transmission
Authors: Klejs Frederik , Lillieholm Mads , Galili Michael , Oxenløwe Leif K.
Published: March 2020

We successfully demonstrate an optical time lens system operating on data signals that are not dispersion compensated after fiber transmission. We demonstrate 4x spectral magnification after 50 km of dispersion un-compensated transmission, with BER <1E-9.
Five-Core × Core Selective Switch and Its Application to Spatial Channel Networking
Authors: Jinno Masahiko , Kodama Takahiro , Ishikawa Tsubasa
Published: March 2020

We design and prototype a 5-core 1 × 6 core selective switch (CSS) with an integrated input and output multi-core-fiber collimator and spatial multiplexer/demultiplexer array. Spatial bypassing and spectral grooming using a CSS-based hierarchical cross-connect are demonstrated.
Low-loss silicon 2 × 4λ multiplexers composed of on-chip polarization-splitter-rotator and 2 × 2 and 2 × 1 Mach-Zehnder filters for 400GbE
Authors: Takano Junya , Fujisawa Takeshi , Sawada Yusuke , Saitoh Kunimasa
Published: March 2020

2×4λ Si-photonics multiplexers for 400GbE composed of Mach-Zehnder filters and a polarization-splitter-rotator are proposed and experimentally demonstrated for the first time. Relative spectral position of two filters is locked by using 2×2 and 2×1 configurations.
Four-channel, Silicon Photonic, Wavelength Multiplexer-Demultiplexer With High Channel Isolations
Authors: Hammood Mustafa , Mistry Ajay , Yun Han , Ma Minglei , Chrostowski Lukas , Jaeger Nicolas A. F.
Published: March 2020

We present a four-channel, silicon-photonic, wavelength multiplexer-demultiplexer made using cascaded contra-directional couplers with adjacent and nonadjacent channel isolations of at least 37 dB and 45 dB, respectively. The device’s maximum insertion-loss is 0.72 dB.
Record 300 Gb/s per Channel 99 GBd PDM-QPSK Full C-Band Transmission over 20570 km Using CMOS DACs
Authors: Arnould Aymeric , Ghazisaeidi Amirhossein , Le Gac Dylan , Ionescu Maria , Brindel Patrick , Renaudier Jeremie
Published: March 2020

We demonstrate a record 300 Gb/s per-channel bitrate over 20570 km across the full C-band. The measured 41 channels are modulated with 99 GBd PDM-QPSK using CMOS DACs and optical pre-emphasis, avoiding nonlinear compensation.
Transmission Performance of Hybrid-Shaped 56APSK Modulation Formats from 34.7 to 74.7 GBd Over Transoceanic Distance
Authors: Cai J. -X. , Mazurczyk M. V. , Patterson W. W. , Davidson C. R. , Hu Y. , Sinkin O. V. , Bolshtyansky M. A. , Foursa D. G. , Pilipetskii A. N.
Published: March 2020

We experimentally study the impact of symbol rate on transmission performance. From 34.7 to 74.7Gbd SNR decreases by ~1.5dB; hardware and nonlinear transmission effects cause 0.7dB and 0.8dB respectively. NLC benefit decreases at higher rates.
LiFi for Industrial Wireless Applications
Authors: Jungnickel Volker , Berenguer Pablo Wilke , Mana Sreelal Maravanchery , Hinrichs Malte , Kouhini Sepideh M. , Bober Kai Lennert , Kottke Christoph
Published: March 2020

We propose a new system concept for LiFi in industrial wireless applications. A distributed multi-user multiple-input multiple-output (MU-MIMO) architecture is used, enabling seamless mobility, reliable low-latency communications, and integration with positioning and 5G.