bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Anti-CD32b Antibodies with Enhanced Fc Function for the Treatment of B and Plasma Cell Malignancies
Authors: Lu Haihui , Molony Ryan D. , Chen Dongshu , Jang Sunyoung , Wolf Babette , Ewert Stefan , Flaherty Meghan , Xu Fangmin , Isim Sinan , Shim Yeonju , Dornelas Christina , Balke Nicole , Leber Xavier Charles , Scharenberg Meike , Koelln Johanna , Choi Eugene , Ward Rebecca , Johnson Jennifer , Calzascia Thomas , Isnardi Isabelle , Williams Juliet A. , Lindenbergh Pieter L. , van de Donk Niels W.C.J. , Mutis Tuna , Huet Heather , Lees Emma , Meyer Matthew J. 
Published: August 2020

AbstractThe sole inhibitory Fcγ receptor CD32b (FcγRIIb) is expressed throughout B and plasma cell development and on their malignant counterparts. CD32b expression on malignant B cells is known to provide a mechanism of resistance to rituximab that can be ameliorated with a CD32b-blocking antibody. CD32b, therefore, represents an attractive tumor antigen for targeting with a monoclonal antibody (mAb). To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. Their complementarity-determining regions (CDR) bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of FcγRIIIa on immune effector cells. The NVS32b mAbs selectively target CD32b+ malignant cells and healthy B cells but not myeloid cells. They mediate potent killing of opsonized CD32b+ cells via antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) as well as complement-dependent cytotoxicity (CDC). In addition, NVS32b CDRs block the CD32b Fc–binding domain, thereby minimizing CD32b-mediated resistance to therapeutic mAbs including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32b+ xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor and enhancement of dendritic cell maturation in response to immune complexes. Finally, the activity of NVS32b mAbs on CD32b+ primary malignant B and plasma cells was confirmed using samples from patients with B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma. The findings indicate the promising potential of NVS32b mAbs as a single agent or in combination with other mAb therapeutics for patients with CD32b+ malignant cells.
Targeted Radionuclide Therapy in Patient-Derived Xenografts Using 177Lu-EB-RGD
Authors: Zhao Liang , Chen Haojun , Guo Zhide , Fu Kaili , Yao Lanling , Fu Li , Guo Weixi , Wen Xuejun , Jacobson Orit , Zhang Xianzhong , Sun Long , Wu Hua , Lin Qin , Chen Xiaoyuan 
Published: August 2020

Abstract
Currently, most patients with non–small cell lung cancer (NSCLC) are diagnosed in advanced stages with a poor five-year survival rate. Therefore, intensive research aimed at finding novel therapeutic strategies has been ongoing; experimental models that reliably emulate NSCLC disease are greatly needed to predict responses to novel therapeutics. Therefore, we developed patient-derived xenograft (PDX) models of NSCLC, which we then used to evaluate the therapeutic efficacy of 177Lu-EB-RGD, a peptide-based radiopharmaceutical with improved pharmacokinetics that targets integrin αvβ3. In this study, three different groups of NSCLC-PDXs were successfully established, all of which maintained the same IHC and genetic characteristics of the human primary tumor. The two NSCLC-PDX groups with intense and low expression of integrin αvβ3 (denoted as PDXαvβ3+ and PDXαvβ3-) were chosen as the experimental models to evaluate the in vivo biological behavior of 177Lu-EB-RGD. In SPECT imaging and biodistribution studies, 177Lu-EB-RGD showed significantly higher accumulation in PDXαvβ3+ and PDXαvβ3- models than its corresponding monomer 177Lu-RGD. A single dose of 18.5 MBq 177Lu-EB-RGD was enough to completely eradicate the tumors in PDXαvβ3+, with no sign of tumor recurrence during the observation period. Such treatment was also efficacious in PDXαvβ3-: a single dose of 29.6 MBq 177Lu-EB-RGD led to a significant delay in tumor growth as compared with that in the control or 177Lu-RGD group. The preclinical data from the use of this model suggest that 177Lu-EB-RGD may be an effective treatment option for NSCLC and should be further evaluated in human trials.
Antihistamine Drug Ebastine Inhibits Cancer Growth by Targeting Polycomb Group Protein EZH2
Authors: Li Qiaqia , Liu Kilia Y. , Liu Qipeng , Wang Guangyu , Jiang Weihua , Meng Qingshu , Yi Yang , Yang Yongyong , Wang Rui , Zhu Sen , Li Chao , Wu Longxiang , Zhao Dongyu , Yan Lin , Zhang Lili , Kim Jung-Sun , Zu Xiongbing , Kozielski Anthony J. , Qian Wei , Chang Jenny C. , Patnaik Akash , Chen Kaifu , Cao Qi 
Published: August 2020

AbstractEnhancer of zester homolog 2 (EZH2), a histone lysine methyltransferase and the catalytic component of polycomb repressive complex 2, has been extensively investigated as a chromatin regulator and a transcriptional suppressor by methylating H3 at lysine 27 (H3K27). EZH2 is upregulated or mutated in most cancers, and its expression levels are negatively associated with clinical outcomes. However, the current developed small-molecule inhibitors targeting EZH2 enzymatic activities could not inhibit the growth and progression of solid tumors. Here, we discovered an antihistamine drug, ebastine, as a novel EZH2 inhibitor by targeting EZH2 transcription and subsequently downregulating EZH2 protein level and H3K27 trimethylation in multiple cancer cell lines at concentrations below 10 μmol/L. The inhibition of EZH2 by ebastine further impaired the progression, migration, and invasiveness of these cancer cells. Overexpression of Ezh2 wild-type and its mutant, H689A (lacking methyltransferase activity), rescued the neoplastic properties of these cancer cells after ebastine treatment, suggesting that EZH2 targeted by ebastine is independent of its enzymatic function. Next-generation RNA-sequencing analysis also revealed that C4-2 cells treated with 8 μmol/L ebastine showed a gene profiling pattern similar to EZH2-knockdown C4-2 cells, which was distinctively different from cells treated with GSK126, an EZH2 enzyme inhibitor. In addition, ebastine treatment effectively reduced tumor growth and progression, and enhanced progression-free survival in triple-negative breast cancer and drug-resistant castration-resistant prostate cancer patient-derived xenograft mice. Our data demonstrated that ebastine is a novel, safe, and potent anticancer agent for patients with advanced cancer by targeting the oncoprotein EZH2.
Circulating Tumor Cells In Advanced Cervical Cancer: NRG Oncology—Gynecologic Oncology Group Study 240 (NCT 00803062)
Authors: Tewari Krishnansu S. , Sill Michael W. , Monk Bradley J. , Penson Richard T. , Moore David H. , Lankes Heather A. , Ramondetta Lois M. , Landrum Lisa M. , Randall Leslie M. , Oaknin Ana , Leitao Mario M. , Eisenhauer Eric L. , DiSilvestro Paul , Van Le Linda , Pearl Michael L. , Burke James J. , Salani Ritu , Richardson Debra L. , Michael Helen E. , Kindelberger David W. , Birrer Michael J. 
Published: August 2020

AbstractTo isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin+/anti-CD45− cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0–18) and, at 36 days posttreatment, was 4 (range, 0–17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79–0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32–1.03) and PFS (HR, 0.59; 95% CI, 0.36–0.96). This effect was not observed with low (&lt; median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker.
Reinstatement of Pimpinella katrajensis R.S.Rao & Hemadri (Apiaceae), an endemic species to Maharashtra with notes on its taxonomy and distribution
Authors: S.M. Deshpande  , S.D. Kulkarni  , R.B. More  , K.V.C. Gosavi  
Published: August 2020

Pimpinella katrajensis Rolla Rao & Hemadri (Apiaceae) is an endemic and less known species, reported from a few localities of Maharashtra. Mukherjee & Constance subsumed P. katrajensis in P. wallichiana Gandhi although both species are very distinct. Thus, the present investigation provides detailed morphological description, distribution, distinguishing characters and images of P. katrajensis for correct identification.
HDL (High-Density Lipoprotein) Remodeling and Magnetic Resonance Imaging–Assessed Atherosclerotic Plaque Burden
Authors: Ben-Aicha Soumaya , Casaní Laura , Muñoz-García Natàlia , Joan-Babot Oriol , Peña Esther , Aržanauskaitė Monika , Gutierrez Manuel , Mendieta Guiomar , Padró Teresa , Badimon Lina , Vilahur Gemma 
Published: August 2020

Objective:
HDL (high-density lipoprotein) role in atherosclerosis is controversial. Clinical trials with CETP (cholesterylester transfer protein)-inhibitors have not provided benefit. We have shown that HDL remodeling in hypercholesterolemia reduces HDL cardioprotective potential. We aimed to assess whether hypercholesterolemia affects HDL-induced atherosclerotic plaque regression.

Approach and Results:

Atherosclerosis was induced in New Zealand White rabbits for 3-months by combining a high-fat-diet and double-balloon aortic denudation. Then, animals underwent magnetic resonance imaging (basal plaque) and randomized to receive 4 IV infusions (1 infusion/wk) of HDL isolated from normocholesterolemic (NC-HDL; 75 mg/kg; n=10), hypercholesterolemic (HC-HDL; 75 mg/Kg; n=10), or vehicle (n=10) rabbits. Then, animals underwent a second magnetic resonance imaging (end plaque). Blood, aorta, and liver samples were obtained for analyses. Follow-up magnetic resonance imaging revealed that NC-HDL administration regressed atherosclerotic lesions by 4.3%, whereas, conversely, the administration of HC-HDLs induced a further 6.5% progression (
P
<0.05 versus basal). Plaque characterization showed that HC-HDL administered animals had a 2-fold higher lipid and cholesterol content versus those infused NC-HDL and vehicle (
P
<0.05). No differences were observed among groups in CD31 levels, nor in infiltrated macrophages or smooth muscle cells. Plaques from HC-HDL administered animals exhibited higher Casp3 (caspase 3) content (
P
<0.05 versus vehicle and NC-HDL) whereas plaques from NC-HDL infused animals showed lower expression of Casp3, Cox1 (cyclooxygenase 1), inducible nitric oxide synthase, and MMP (metalloproteinase) activity (
P
<0.05 versus HC-HDL and vehicle). HDLs isolated from animals administered HC-HDL displayed lower antioxidant potential and cholesterol efflux capacity as compared with HDLs isolated from NC-HDL-infused animal and vehicle or donor HDL (
P
<0.05). There were no differences in HDL-ApoA1 content, ABCA1 (ATP-binding cassette transporter A1) vascular expression, and SRB1 (scavenger receptor B1) and ABCA1 liver expression.

Conclusions:
HDL particles isolated from a hypercholesterolemic milieu lose their ability to regress and stabilize atherosclerotic lesions. Our data suggest that HDL remodeling in patients with co-morbidities may lead to the loss of HDL atheroprotective functions.
Arterial Structure and Stiffness Are Altered in Young Adults Born Preterm
Authors: Flahault Adrien , Oliveira Fernandes Rafael , De Meulemeester Julie , Ravizzoni Dartora Daniela , Cloutier Anik , Gyger Geneviève , El-Jalbout Ramy , Bigras Jean-Luc , Luu Thuy Mai , Nuyt Anne Monique 
Published: August 2020

Objective:
Preterm birth has been associated with changes in arterial structure and function. Association with complications occurring during the neonatal period, including bronchopulmonary dysplasia, on vascular outcomes in adulthood is unknown.

Approach and Results:
We evaluated a cohort of 86 adults born preterm (below 30 weeks of gestation), compared to 85 adults born term, at a mean age of 23 years. We performed ultrasonographic assessment of the dimensions of the ascending aorta, carotid and brachial arteries, and estimated flow-mediated dilation, carotid-femoral pulse wave velocity, augmentation index corrected for heart rate, and carotid intima-media thickness. All analyses were performed with and without adjustment for potential confounding variables, including height, sex, and body mass index. Ascending aorta diameter in diastole was smaller in the preterm group, but carotid and brachial arteries were similar. Carotid and brachial strain, a marker of arterial distensibility, was smaller in the preterm group, while carotid-femoral pulse wave velocity, was similar between groups, indicating similar aortic stiffness. Carotid intima-media thickness, endothelial function flow-mediated dilation, blood nitrite, and nitrate levels were similar between groups. Individuals with bronchopulmonary dysplasia had lower brachial artery strain suggesting long-term association of this neonatal complication with vascular structure. Diastolic blood pressure was higher in the preterm group and was associated with decreased brachial and carotid distensibility.

Conclusions:
Young adults born preterm display alterations in arterial distensibility that are associated with a history of bronchopulmonary dysplasia.
Patterns of Postpartum Ambulatory Care Follow‐up Care Among Women With Hypertensive Disorders of Pregnancy
Authors: Lewey Jennifer , Levine Lisa D. , Yang Lin , Triebwasser Jourdan E. , Groeneveld Peter W. 
Published: August 2020

Background
Preeclampsia and gestational hypertension are hypertensive disorders of pregnancy (HDP) that identify an increased risk of developing chronic hypertension and cardiovascular disease later in life. Postpartum follow‐up may facilitate early screening and treatment of cardiovascular risk factors. Our objective is to describe patterns of postpartum visits with primary care and women's health providers (eg, family medicine and obstetrics) among women with and without HDP in a nationally representative sample of commercially insured women.

Methods and Results

We conducted a retrospective cohort study using insurance claims from a US health insurance database to describe patterns in office visits in the 6 months after delivery. We identified 566 059 women with completed pregnancies between 2005 and 2014. At 6 months, 13% of women with normotensive pregnancies, 18% with HDP, and 23% with chronic hypertension had primary care visits (
P
<0.0001 for comparing HDP and chronic hypertension groups with control participants). Only 58% of women with HDP had 6‐month follow‐up with any continuity provider compared with 47% of women without hypertension (
P
<0.0001). In multivariable analysis, women with severe preeclampsia were 16% more likely to have postpartum continuity follow‐up (adjusted odds ratio, 1.16; 95% CI, 1.2–1.21). Factors associated with a lower likelihood of any follow‐up included age ≥30 years, Black race, Hispanic ethnicity, and having multiple gestations.

Conclusions
Rates of continuity care follow‐up after a pregnancy complicated by hypertension were low. This represents a substantial missed opportunity to provide cardiovascular risk screening and management to women at increased risk of future cardiovascular disease.
What Did the Psalmist Say about His Hands and Feet in Psalm 22:17?
Authors: Flowers Michael V. 
Published: August 2020

Abstract
Ps 22:17 is among the most controverted verses in the Hebrew Bible, both with respect to its original text and original meaning. The biggest question that text critics and interpreters struggle to answer is what the psalmist said concerning his hands and feet. With so many proposals now on the table and with debates on this text having reached an impasse, it seemed like it would be helpful to present the status quaestionis with regard to this text. Thirteen different proposals are therefore analyzed with a view to their respective merits and demerits. The goal here is to eliminate the proposals that seem least viable and to become more self-conscious about how we judge between the others.
For the People, By the Viewpoints? Realism and Idealism in Public Reason
Authors: Jayaram Athmeya 
Published: August 2020

Abstract
Since John Rawls, public reason theorists have attempted to show how liberal political norms could be acceptable to people with diverse religious and ethical viewpoints. However, these theories overlook the importance of the distinction between acceptability to realistic people and acceptability to viewpoints, which matters because public reason theories are committed to the former, but only deliver the latter, thereby failing to justify liberal norms. Public reason theories therefore face a dilemma: abandon realistic people and lose normative appeal, or retain realism and find a new way to justify liberalism.
Effect of Swell on Wind Stress for Light to Moderate Winds
Authors: Vincent Charles L. , Graber Hans C. , Collins Clarence O. 
Published: August 2020

AbstractBuoy observations from a 1999 Gulf of Mexico field program (GOM99) are used to investigate the relationships among friction velocity u*, wind speed U, and amount of swell present. A U–u*sea parameterization is developed for the case of pure wind sea (denoted by u*sea), which is linear in U over the range of available winds (2–16 m s−1). The curve shows no sign of an inflection point near 7–8 m s−1 as suggested in a 2012 paper by Andreas et al. on the basis of a transition from smooth to rough flow. When observations containing more than minimal swell energy are included, a different U–u* equation for U < 8 m s−1 is found, which would intersect the pure wind-sea curve about 7–8 m s−1. These two relationships yield a bilinear curve similar to Andreas et al. with an apparent inflection near 7–8 m s−1. The absence of the inflection in the GOM99 experiment pure wind-sea curve and the similarity of the GOM99 swell-dominated low wind speed to Andreas et al.’s low wind speed relationship suggest that the inflection may be due to the effect of swell and not a flow transition. Swell heights in the range of only 25–50 cm may be sufficient to impact stress at low wind speeds.
Implementing a Parallel Version of a Variational Scheme in a Global Assimilation System at Eddy-Resolving Resolution
Authors: Cipollone Andrea , Storto Andrea , Masina Simona 
Published: August 2020

AbstractRecent advances in global ocean prediction systems are fostered by the needs of accurate representation of mesoscale processes. The day-by-day realistic representation of its variability is hampered by the scarcity of observations as well as the capability of assimilation systems to correct the ocean states at the same scale. This work extends a 3DVAR system designed for oceanic applications to cope with global eddy-resolving grid and dense observational datasets in a hybridly parallelized environment. The efficiency of the parallelization is assessed in terms of both scalability and accuracy. The scalability is favored by a weak-constrained formulation of the continuity requirement among the artificial boundaries implied by the domain decomposition. The formulation forces possible boundary discontinuities to be less than a prescribed error and minimizes the parallel communication relative to standard methods. In theory, the exact solution is recovered by decreasing the boundary error toward zero. In practice, it is shown that the accuracy increases until a lower bound arises, because of the presence of the mesh and the finite accuracy of the minimizer. A twin experiment has been set up to estimate the benefit of employing an eddy-resolving grid within the assimilation step, as compared with an eddy-permitting one, while keeping the eddy-resolving grid within the forecast step. It is shown that the use of a coarser grid for data assimilation does not allow an optimal exploitation of the present remote sensing observation network. A global decrease of about 15% in the error statistics is found when assimilating dense surface observations, and no significant improvement is seen for sparser observations (in situ profilers).
Longitudinal Voice Outcomes Following Serial Potassium Titanyl Phosphate Laser Procedures for Recurrent Respiratory Papillomatosis
Authors: Hung Wei-Chen , Lo Wu-Chia , Fang Kai-Min , Cheng Po-Wen , Wang Chi-Te 
Published: August 2020

Objective: Repeated surgical interventions are usually required to control recurrent respiratory papillomatosis (RRP), but at considerable risk of worsened postoperative voice quality. Potassium titanyl phosphate (KTP) laser has been reported to effectively manage RRP; however, voice quality after repeated procedures has not been investigated. Methods: This study recruited 16 patients with RRP treated using KTP laser between 2013 and 2019. KTP laser procedures were performed under general anesthesia via direct suspension laryngoscope or under local anesthesia via flexible endoscope, depending on the need for pathological proof, patient tolerance, and lesion size and location. Disease control was investigated by videolaryngostroboscopy. Voice outcome was evaluated using a 10-item voice handicap index (VHI-10), acoustic and perceptual analyzes. Results: We reviewed the medical records of 11 male and 5 female patients with RRP (age range: 23-73 years). Five patients received KTP laser once, six patients received it 2 to 5 times, and five patients received 6 to 15 procedures. Median VHI-10 decreased from 28.3 to 12.0 points after the initial procedure and were maintained at 10.1 to 11.0 points following subsequent procedures ( P < .01, generalized estimating equation). Acoustic and perceptual analysis of voice quality also revealed significant improvements ( P < .01), which remained stable even after 6 to 10 KTP laser procedures. Minor adverse events included slight fibrotic change of vocal folds and glottic web, but these did not significantly alter postoperative voice quality. Conclusion: This longitudinal follow-up study revealed that serial KTP laser procedures can effectively control RRP while preserving phonatory function and maintaining adequate voice quality. Level of Evidence: 4