bluuebunny/crossref_metadata_2025_split huggingface dataset:
The DIAL Study (Dual Immunomodulation in Aggressive Lymphoma): A randomized phase 2 study of CDX-1127 (varlilumab) in combination with nivolumab in patients with relapsed or refractory aggressive B-cell lymphomas (NCI 10089/NCT03038672).
Authors: Villasboas Jose Caetano , Reeder Craig B. , Tun Han W. , Bartlett Nancy L. , Sharon Elad , LaPlant Betsy , Adjei Alex A. , Ansell Stephen M. 
Published: March 2020

TPS7570 Background: The DIAL study is testing the efficacy of dual immunomodulation in patients with advanced B cell non-Hodgkin lymphoma (B-NHL). Developed by the Cancer Therapy Evaluation Program (CTEP), the trial combines the use of a programmed cell death protein 1 (PD-1) inhibitor (nivolumab) with an agonist of the CD27 receptor (varlilumab) in a randomized phase 2 design. CD27, a co-stimulatory receptor, regulates T cell activation through interaction with CD70. T cell exhaustion plays a major role in immune evasion in B-NHL. Varlilumab is an agonistic IgG1 monoclonal antibody that recognizes CD27 leading to prevention or reversal of exhaustion. Varlilumab also demonstrates direct anti-tumoral activity in xenograft models of human lymphoma cell lines via antibody-dependent cell-mediated cytotoxicity. Phase 1 data supports the safety and tolerability of single-agent varlilumab in advanced hematologic malignancies. We hypothesize that CD27 activation synergizes with PD-1 inhibition resulting in a superior anti-lymphoma effect compared to PD-1 blockade alone. The study will also evaluate the effect of these agents on tumor and immune cells using IHC, mass cytometry (CyTOF), multiplex ELISA, imaging mass cytometry, and whole exome sequencing. Methods: The trial is enrolling patients with advanced aggressive B-NHL. Standard inclusion criteria and prior treatment with at least 2 lines of standard therapy are required. Prior autologous stem cell transplant and/or chimeric antigen receptor (CAR) T cell therapy is allowed. Patients with active CNS disease are excluded. Eligible patients will be randomized to treatment with single-agent nivolumab (group 1) or dual immunotherapy with nivolumab and varlilumab. Group 1 is allowed to cross-over at the time of progression. Nivolumab will be administered intravenously (IV) every 2 weeks (240 mg) for 4 months followed by monthly dosing thereafter (480 mg). Varlilumab will be given IV every 4 weeks (3 mg/kg). Response assessment will be done by PET-CT scan every 12 weeks. Primary outcome is overall response rate (ORR) according to the LYRIC criteria. The trial will enroll 48 patients per arm, allowing 80% power to detect at least 20% increase in ORR in the experimental arm (group 2) assuming a 25% ORR in the control arm (group 1). The trial is registered and open to participation to members of ETCTN and EDDOP. Clinical trial information: NCT03038672.
POLARIX: A phase 3 study of polatuzumab vedotin (pola) plus R-CHP versus R-CHOP in patients (pts) with untreated DLBCL.
Authors: Tilly Herve , Flowers Christopher , Friedberg Jonathan W. , Herbaux Charles , Morschhauser Franck , Sehn Laurie Helen , Sharman Jeff Porter , Trneny Marek , Lee Calvin , Salles Gilles A. 
Published: March 2020

TPS7571 Background: Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) remains the standard of care in pts with previously untreated diffuse large B-cell lymphoma (DLBCL) but outcomes remain poor in pts with high-risk disease. Pola is an antibody–drug conjugate targeting CD79b; it delivers the antimitotic agent monomethyl auristatin E. Addition of pola to bendamustine and R in pts with transplant-ineligible DLBCL resulted in improved OS (Sehn et al, 2018). In front-line treatment of DLBCL, pola is being evaluated as a replacement for vincristine within the R-CHOP regimen. In a phase Ib/II study in pts with higher risk DLBCL, pola + R-CHP demonstrated promising efficacy and a safety profile similar to that observed in the R-CHOP arm of the GOYA study (Tilly et al, 2017; Vitolo et al, 2017). The phase 3 POLARIX study investigates pola + R-CHP in untreated DLBCL. Methods: POLARIX is an ongoing, international, randomized, double-blind, active-placebo-controlled, phase 3 study in pts with previously untreated DLBCL. Pts aged 18–80 years with CD20-positive DLBCL (including DLBCL not otherwise specified, GCB, and ABC subtypes), ECOG performance status 0–2, and IPI score 2–5, are stratified by IPI score (2 vs 3–5), bulky disease and geographical region and randomized (1:1). Pts receive 6 cycles of either: pola 1.8 mg/kg on Day 1 plus R-CHP (standard dosing schedule) plus vincristine placebo; or pola placebo plus R-CHOP (standard dosing schedule). R monotherapy is administered in cycles 7 and 8 (both arms). PET-CT and CT scans are obtained at screening, after 4 cycles (planned interim assessment), and 6–8 weeks after end of study treatment. Follow-up will continue for 5 years after treatment. Primary endpoint: investigator-assessed progression-free survival (PFS; Lugano classification). Secondary endpoints: independent review committee-assessed PET-CT complete response rate at end of treatment, event-free survival, 2-year PFS rate, and OS. Enrolment began Nov 2017. This trial is currently recruiting, and plans to enrol 875 patients in 24 countries. Clinical trial information: NCT03274492.
Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab (DARA) in patients (pts) with newly diagnosed multiple myeloma (NDMM) for whom transplant is not planned as initial therapy: A multicenter, randomized, phase III study (CEPHEUS).
Authors: Zweegman Sonja , Usmani Saad Zafar , Chastain Katherine , Carey Jodi , Ren Karen , Smith Elena , Krevvata Maria , Wang Jianping , Vermeulen Jessica , Facon Thierry 
Published: March 2020

TPS8056 Background: DARA is a human, anti-CD38 IgGκ monoclonal antibody that significantly reduced the risk of progression/death with a manageable safety profile across several phase 3 studies in relapsed/refractory MM and NDMM. DARA + VRd (D-VRd) demonstrated efficacy and tolerability in the safety run-in cohort of the ongoing phase 2 GRIFFIN study that included transplant-eligible NDMM pts. To determine whether D-VRd demonstrates efficacy and tolerability in NDMM pts for whom transplant is not intended as initial therapy, the phase 3 CEPHEUS study will evaluate the efficacy and safety of D-VRd vs VRd alone in this pt population. Methods: This is an ongoing multicenter, open-label, randomized phase 3 study of D-VRd vs VRd alone in pts with NDMM for whom transplant is not intended as initial therapy. Approximately 360 pts will be stratified by ISS stage and age/transplant eligibility (age < 70 years and transplant-ineligible, or age < 70 years and refusal to transplant, or age ≥70 years) and will be randomized in a 1:1 ratio. All pts will receive eight 21-day cycles of VRd (V: 1.3 mg/m2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-14; d: 20 mg PO/IV Days 1, 2, 4, 5, 8, 9, 11, 12), followed by 28-day cycles of Rd (R: 25 mg PO Days 1-21; d: 40 mg PO/IV Days 1, 8, 15, 22) until progressive disease (PD). Patients in the DARA group will also receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) weekly in Cycles 1-2, every 3 weeks in Cycles 3-8, and every 4 weeks in Cycles 9+ until PD. All pts will receive preinfusion medications. Minimal residual disease (MRD)-negative rate at 10–5 sensitivity threshold by NGS is the primary endpoint. MRD will be evaluated at suspected complete response or better. Secondary endpoints include progression-free survival (PFS), MRD-negative rate at 1-year, durable MRD negativity, overall response rate, time to and duration of response, PFS on next line of therapy, overall survival, clinical efficacy in high-risk molecular subgroups, health-related quality of life, pharmacokinetics, immunogenicity, and safety. Clinical trial information: NCT03652064.
Phase 2 trial of first-line pembrolizumab with platinum doublet chemotherapy and radiotherapy in patients (pts) with unresectable, locally advanced stage III non–small-cell lung cancer (NSCLC): KEYNOTE-799.
Authors: Jabbour Salma K. , Park Keunchil , Cohn Dosinda , Liu Hong , Keller Steven M. , Kowalski Dariusz M. 
Published: March 2020

TPS8575 Background: Standard therapy for pts with unresectable stage III NSCLC is concurrent platinum doublet chemotherapy with radiotherapy (CCRT); however, this therapy does not reduce the risk of distant relapse, and the 5-y survival rate is low. The anti–PD-1 checkpoint inhibitor pembrolizumab has durable clinical activity as first-line therapy for advanced/metastatic NSCLC: as monotherapy for PD-L1–positive tumors and in combination with chemotherapy irrespective of PD-L1 status. KEYNOTE-799 evaluates the safety/efficacy of first-line pembrolizumab plus CCRT for unresectable, locally advanced stage III NSCLC. Methods: This nonrandomized, open-label phase 2 study enrolls pts ≥18 y with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC with measurable disease per RECIST 1.1. Pts receive 17 cycles of pembrolizumab 200 mg Q3W plus standard thoracic radiotherapy in cycles 2 and 3 (60 Gy in 30 daily 2 Gy fractions). In cycles 1–3, treatment also includes investigator’s choice of either paclitaxel 200 mg/m2 and carboplatin area under the curve (AUC) 6 Q3W for 1 cycle, followed by paclitaxel 45 mg/m2 and carboplatin AUC 2 weekly for 6 weeks, or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 Q3W (nonsquamous only). Tumor imaging occurs at baseline and Q9W until week 54, verified PD, initiation of new cancer therapy, study withdrawal, or death. AEs are graded by NCI CTCAE v4.0. Primary endpoints are the rate of grade ≥3 pneumonitis and ORR (RECIST 1.1 by blinded independent central review [BICR]); confidence intervals for both will be estimated by the Clopper-Pearson method. Secondary endpoints are PFS (RECIST 1.1 modified to follow ≤10 target lesions; ≤5 per organ by BICR), OS, and safety. PFS and OS will be analyzed by Kaplan-Meier method. Approximately 216 pts (108 per cohort) will be enrolled in 59 sites in 10 countries beginning on Nov 5, 2018. As of Feb 12, 2019, 30 pts have enrolled. Continuous interim analyses using binomial sequential testing will be performed after ≥36 pts have ≥15 weeks of follow up in each cohort, to allow earlier treatment discontinuation, if required. Clinical trial information: NCT03631784.
Acute Hyperketonemia Does Not Affect Glucose or Palmitate Uptake in Abdominal Organs or Skeletal Muscle
Authors: Lauritsen Katrine M , Søndergaard Esben , Luong Thien V , Møller Niels , Gormsen Lars C 
Published: March 2020

Abstract

Context
It has recently been hypothesized that ketone bodies may have independent cardioprotective effects due to increased myocardial efficiency and that this may explain the improved survival of individuals with type 2 diabetes treated with mildly ketogenic sodium–glucose cotransporter-2 inhibitors.

Objective
To determine whether ketone bodies are selectively utilized in tissues critical for preservation of conscience and circulation. We investigated the effect of acute hyperketonemia on substrate metabolism in less prioritized tissues such as abdominal organs, adipose tissue, and skeletal muscle.

Design
Acute, randomized, single-blinded, crossover design.

Setting
Ambulatory care.

Participants
Eight healthy participants completed the study. Two additional participants withdrew because of claustrophobia during the scans.

Intervention
Infusions of saline and ketone bodies during a hyperinsulinemic-euglycemic clamp.

Main Outcome Measures
Organ-specific glucose and palmitate uptake was determined by dynamic positron emission tomography/computed tomography (PET/CT) scans with 18F-fluorodeoxyglucose (18F-FDG) and 11C-palmitate. Blood flow to abdominal organs was measured with O-15-labeled water (15O-H2O) perfusion PET. The study was performed as a post hoc analysis.

Results
We found that ketone body infusion did not affect glucose uptake, palmitate uptake, or blood flow to abdominal organs and skeletal muscles.

Conclusion
Acute hyperketonemia does not affect glucose or palmitate uptake in skeletal muscle or abdominal tissues, supporting the notion that ketone bodies are selectively used by critical organs such as the heart and brain.
Quantum Chemical Reaction Prediction Method Based on Machine Learning
Authors: Fujinami Mikito , Seino Junji , Nakai Hiromi 
Published: March 2020

Abstract
A quantum chemical reaction prediction (QC-RP) method based on machine learning was developed to predict chemical products from given reactants. The descriptors contain atomic information in reactants such as charge, molecular structure, and atomic/molecular orbitals obtained by the quantum chemical calculations. The QC-RP method involves two procedures, namely, learning and prediction. The learning procedure constructs screening and ranking classifiers using 1625 polar and 95 radical reactions in a textbook of organic chemistry. In the prediction procedure, the screening classifier distinguishes reactive and unreactive atoms and the ranking one provides reactive atom pairs in ranking order. Numerical assessments confirmed the high accuracies both of the screening and ranking classifiers in the prediction procedures. Furthermore, an analysis on the classifiers unveiled important descriptors for the prediction.
Pixel super-resolved lens-free on-chip microscopy based on dual laterally shifting modulation
Authors: Zhang He , Wang Weibo , Liu Chenguang , Liu Jian 
Published: March 2020

Achieving high spatial resolution over a wide field of view (FOV) is the goal of many imaging systems. In a traditional lens-based microscope, designing a complex objective with high numerical aperture (NA) to achieve this goal is a tough and challenging task. The lens-free wide-field imaging method based on phase retrieval provides a new way to bypass the trade-off between the spatial resolution and FOV of conventional microscopy. However, the typical lens-free microscopy usually requires mechanical devices with high precision and repeatability. In this paper, we report a robust and cost-effective pixel super-resolved lens-free imaging method based on dual laterally shifting modulation. A thin diffuser is inserted between the object and the image sensor to be used as the modulator. The diffuser and the object are transversely scanned at the same time to add diversities for phase retrieval and pixel super-resolution, respectively. In this way, the positional shifts of the diffuser and the object can be directly recovered with the registration algorithm, thus addressing the low stability and inaccuracy issues of translation stages. We also propose a pixel super-resolution phase-retrieval algorithm to recover the object and the unknown diffuser. We first use numerical simulations to evaluate the proposed scheme. Then, we validate this approach by imaging a resolution target and a pollen sample, thus achieving an FOV of

∼

30

mm
2

and a half-pitch resolution of 0.78 µm, which surpasses 2.14 times the theoretical Nyquist–Shannon sampling resolution limit. Finally, the 3D refocusing ability is also verified by imaging a thick mosquito sample.
Width determination for deep grooves based on a variable point spread function imaging model
Authors: You Xiaoyu , Wang Yuhang , Leach Richard , Gu Kang , Shi Yushu , Zhang Shu , Liu Jian 
Published: March 2020

In three-dimensional confocal microscopy, two-dimensional width measurement can be significantly influenced by the groove height. The groove height not only results in deformation of the input light field due to the effect of edge occlusions, but also introduces a defocus error to the detection plane. This paper proposes a new, to the best of our knowledge, edge-setting method to determine groove width, which engineers the point spread function to correct for the groove edge obstruction effect and develops an edge obstruction imaging model (EOIM) based on the variable point spread function. This model gives a relationship between the groove height and the normalized intensity at the groove edge and can use this relationship to determine the groove edge position that would result from focusing at the groove’s lower surface. Experimental results show that an EOIM-based width determination method is more accurate than the traditional 1/4 edge-setting method. Compared to the 1/4 edge-setting method, the deviation from a reference width measured with traceable scanning electron microscopy is reduced by a factor of 2.1 with a 1.3 times smaller standard deviation.
On-chip silicon shallowly etched TM0-to-TM1 mode-order converter with high conversion efficiency and low modal crosstalk
Authors: Xu Yin , Zhu Chenxi , Hu Xin , Dong Yue , Zhang Bo , Ni Yi 
Published: March 2020

Ever-increasing capacity requirements of optical interconnects drive the emergence and fast development of mode-division-multiplexing (MDM) transmission on-chip, where efficient mode control and conversion components become indispensable. Here, we propose an on-chip silicon

TM
0

-

to

-

TM
1

mode-order converter by leveraging shallowly etched rectangular slots on the top surface of silicon nanowire. The mode conversion region consists of two rectangular slots on the same side of a silicon nanowire and a smaller one between them to realize the efficient mode-order conversion from input

TM
0

to output

TM
1

mode with the help of multimode interference and accumulated phase difference. By studying the etching pattern on the silicon nanowire in detail, we have achieved an on-chip

TM
0

-

to

-

TM
1

mode-order converter with a high conversion efficiency of 97.5% and low modal crosstalk

<

−

23

dB

in a conversion length of 11.8 µm; further, the insertion loss is only 0.29 dB at the wavelength of 1.55 µm. Moreover, the device working bandwidth and fabrication tolerance are also analyzed. Note that the proposed shallowly etched slots on the silicon nanowire can also be further developed to achieve the on-chip

TM
0

-

to

-

TM
2

mode-order conversion. With these characteristics, such a device could boost the development of MDM transmission on-chip with more TM-polarized mode channels.
Diagnosis and Treatment of Duodenal Gastrointestinal Stromal Tumors
Authors: Du Haojie , Ning Longgui , Li Sha , Lou Xinhe , Chen Hongtan , Hu Fengling , Shan Guodong , Zhang Fenming , Xu Guoqiang 
Published: March 2020

OBJECTIVES:
The diagnostic value of different noninvasive diagnostic modalities and the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) reliability of duodenal gastrointestinal stromal tumors (GISTs) are ambiguous in the present studies.

METHODS:
Patients with a histopathological diagnosis of the primary duodenal GISTs between the years 2008 and 2018 were analyzed. Data on the treatment and clinicopathological features were recorded. Furthermore, the computed tomography (CT)/magnetic resonance imaging (MRI), EUS, and EUS-FNA results were collected and compared.

RESULTS:
A total of 142 patients were enrolled into the study. In all patients, the most common symptom was gastrointestinal bleeding (44.4%), followed by abdominal pain and bloating (27.5%). Duodenal GISTs were mostly located in the second duodenal portion (52.1%), followed by the first portion (19.0%). EUS had significantly higher sensitivity and positive predictive values than CT or MRI (P = 0.047 and P = 0.005, respectively). The EUS-FNA sensitivity of duodenal GISTs was also significantly higher than the conventional endoscopic biopsy (73.3% vs 33.3%, P = 0.006). A total of 131 patients underwent surgery, including limited resection or pancreaticoduodenectomy. The tumor size and postoperative complication rates were higher in patients who underwent pancreaticoduodenectomy (P = 0.001 and P < 0.001, respectively).

DISCUSSION:
The diagnostic value of EUS is significantly higher than that of CT and MRI for duodenal GISTs. The EUS-FNA can provide a histological diagnosis of duodenal GISTs in most cases.
Guarding the Guardians: Fictional Representation of Manipulated and Fake News in Graham Greene’s Work
Authors: Jiménez Beatriz Valverde , Pérez-Escolar Marta 
Published: March 2020

Abstract
Drawing upon mass communication theories, concretely Walter Lippman’s theory of stereotypes, Erving Goffman’s theory of frames, and Jean Baudrillard’s theory of simulacra and simulation, we examine the fictional representation of manipulated and fake news in three novels by Graham Greene, Stamboul Train (1932), The Quiet American (1955), and A Burnt-Out Case (1960). In this paper, within the frame of one of the key concepts in his work, the ‘virtue of disloyalty’, we argue that Greene’s fictional representation of journalism (mal)practice constitutes a piece of grit in the machinery of the western press, questioning the political and cultural dominant discourse conveyed to the public. In this line, Greene’s literary representations of the journalistic practice can be read as indicators (and, in turn, shapers) of the western culture’s prevailing perceptions of the reported news and the professionals that convey the facts to a general public. With his fictional representation of the profession of journalism, Greene makes readers aware of the way information can be manipulated and the necessity of developing a critical mind concerning the news and how they are conveyed through the media.
The Contemporary South African Trauma Novel: Michiel Heyns’Lost Ground(2011) and Marlene van Niekerk’sThe Way of the Women(2008)
Authors: Mengel Ewald 
Published: March 2020

AbstractAfter the end of apartheid in 1990 and the new constitution of 1994, the genre of the contemporary South African novel is experiencing a heyday. One reason for this is that, with the end of censorship, the authors can go about unrestraint to take a critical look at the traumatized country and the state of a nation that shows a great need to come to terms with its past. In this context, trauma and narration prove to be a fertile combination, an observation that stands in marked contrast to the deconstructionist view of trauma as ‘unclaimed’ experience and the inability to speak about it.Michiel Heyns’Lost Ground(2011) and Marlene van Niekerk’sThe Way of the Women(2008) are prime examples of the contemporary South African trauma novel. As crime fiction,Lost Groundnot only tells a thrilling story but is also deeply involved in South African politics. The novelist Heyns plays with postmodernist structures, but the real strength of the novel lies in its realistic milieu description and the analysis of the protagonist’s traumatic ‘entanglements’.The Way of the Womenis mainly a farm novel but also shows elements of the historical novel and the marriage novel. It continues the process of the deconstruction of the farm as a former symbol of the Afrikaner’s pride and glory. Both novels’ meta-fictional self-reflections betray the self-consciousness of their authors who are aware of the symbolization compulsions in a traumatized country. They use narrative as a means of ‘working through’, coming to terms with trauma, and achieving reconciliation. Both novels’ complex narrative structures may be read as symbolic expressions of traumatic ‘entanglements’ that lie at the heart of the South African dilemma.