bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor
Authors: Curti Brendan D , Koguchi Yoshinobu , Leidner Rom S , Rolig Annah S , Sturgill Elizabeth R , Sun Zhaoyu , Wu Yaping , Rajamanickam Venkatesh , Bernard Brady , Hilgart-Martiszus Ian , Fountain Christopher B , Morris George , Iwamoto Noriko , Shimada Takashi , Chang ShuChing , Traber Peter G , Zomer Eliezer , Horton J Rex , Shlevin Harold , Redmond William L 
Published: April 2021

BackgroundPD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC).MethodsWe performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404). Belapectin was administered at 2, 4, or 8 mg/kg IV 60 min before pembrolizumab (200 mg IV every 3 weeks for five cycles). Responding patients continued pembrolizumab monotherapy for up to 17 cycles. Main eligibility requirements were a functional Eastern Cooperative Oncology Group status of 0–2, measurable or assessable disease, and no active autoimmune disease. Prior T-cell checkpoint antibody therapy was permitted.ResultsObjective response was observed in 50% of MM (7/14) and and 33% of HNSCC (2/6) patients. Belapectin+pembrolizumab was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab monotherapy. There were no dose-limiting toxicities for belapectin within the dose range investigated. Significantly increased effector memory T-cell activation and reduced monocytic myeloid-derived suppressor cells (M-MDSCs) were observed in responders compared with non-responders. Increased baseline expression of Gal-3+ tumor cells and PD-1+CD8+ T cells in the periphery correlated with response as did higher serum trough levels of pembrolizumab.ConclusionsBelapectin+pembrolizumab therapy has activity in MM and HNSCC. Increased Gal-3 expression, expansion of effector memory T cells, and decreased M-MDSCs correlated with clinical response. Further investigation is planned.
Whole-genome re-sequencing reveals genome-wide variations between the peach variety Green No. 9 and its bud mutant Daifei
Authors: Li Guixiang , Li Miao , Liu Wei , Dong Xiaomin , Gao Xiaolan , Zhang Anning 
Published: April 2021

Whole-genome sequencing technologies provide opportunities to further understand genetic variation among different varieties. Some related genes that are useful for the breeding process could be identified by sequencing technologies. In this study, two peach varieties, Green No. 9 (LH) and its bud mutant Daifei (DT), were analyzed with whole-genome re-sequencing. Approximately 109 million total reads were generated, which covered ∼89% of the peach reference genome. A total of 1 143 757 single nucleotide polymorphisms (SNPs), 169 827 insertion–deletion mutations (InDels), 17 132 structural variations (SVs) and 5 040 copy number variations (CNVs) were detected in Green No. 9 and Daifei. Variant genes were classified by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway database. Detected genes such as LOC18768059 (carbohydrate metabolism) and LOC18785045 (anthocyanin biosynthesis), were good candidate genes for exploring the phenotypic variations between Green No. 9 and Daifei. Green No. 9 and its bud mutant Daifei showed obvious differences in phenotypes and variant genetic loci. The detected genomic variations will contribute to explorations of important functional genes and to understanding the genetic basis of peach bud mutations.
IFNγ Is Critical for CAR T Cell–Mediated Myeloid Activation and Induction of Endogenous Immunity
Authors: Alizadeh Darya , Wong Robyn A. , Gholamin Sharareh , Maker Madeleine , Aftabizadeh Maryam , Yang Xin , Pecoraro Joseph R. , Jeppson John D. , Wang Dongrui , Aguilar Brenda , Starr Renate , Larmonier Claire B. , Larmonier Nicolas , Chen Min-Hsuan , Wu Xiwei , Ribas Antoni , Badie Behnam , Forman Stephen J. , Brown Christine E. 
Published: April 2021

Abstract

Chimeric antigen receptor (CAR) T cells mediate potent antigen-specific antitumor activity; however, their indirect effects on the endogenous immune system are not well characterized. Remarkably, we demonstrate that CAR T-cell treatment of mouse syngeneic glioblastoma (GBM) activates intratumoral myeloid cells and induces endogenous T-cell memory responses coupled with feed-forward propagation of CAR T-cell responses. IFNγ production by CAR T cells and IFNγ responsiveness of host immune cells are critical for tumor immune landscape remodeling to promote a more activated and less suppressive tumor microenvironment. The clinical relevance of these observations is supported by studies showing that human IL13Rα2–CAR T cells activate patient-derived endogenous T cells and monocytes/macrophages through IFNγ signaling and induce the generation of tumor-specific T-cell responses in a responding patient with GBM. These studies establish that CAR T-cell therapy has the potential to shape the tumor microenvironment, creating a context permissible for eliciting endogenous antitumor immunity.

Significance:
Our findings highlight the critical role of IFNγ signaling for a productive CAR T-cell therapy in GBM. We establish that CAR T cells can activate resident myeloid populations and promote endogenous T-cell immunity, emphasizing the importance of host innate and adaptive immunity for CAR T-cell therapy of solid tumors.
This article is highlighted in the In This Issue feature, p. 2113
Dapagliflozin and Recurrent Heart Failure Hospitalizations in Heart Failure With Reduced Ejection Fraction: An Analysis of DAPA-HF
Authors: Jhund Pardeep S. , Ponikowski Piotr , Docherty Kieran F. , Gasparyan Samvel B. , Böhm Michael , Chiang Chern-En , Desai Akshay S. , Howlett Jonathon , Kitakaze Masafumi , Petrie Mark C. , Verma Subodh , Bengtsson Olof , Langkilde Anna-Maria , Sjöstrand Mikaela , Inzucchi Silvio E. , Køber Lars , Kosiborod Mikhail N. , Martinez Felipe A. , Sabatine Marc S. , Solomon Scott D. , McMurray John J.V. 
Published: April 2021

Background:
Patients with heart failure (HF) and reduced ejection fraction will experience multiple hospitalizations for heart failure during the course of their disease. We assessed the efficacy of dapagliflozin on reducing the rate of total (ie, first and repeat) hospitalizations for heart failure in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure).

Methods:
The total number of HF hospitalizations and cardiovascular deaths was examined by using the proportional-rates approach of Lei-Wei-Yang-Ying and a joint frailty model for each of recurrent HF hospitalizations and time to cardiovascular death. Variables associated with the risk of recurrent hospitalizations were explored in a multivariable Lei-Wei-Yang-Ying model.

Results:

Of 2371 participants randomly assigned to placebo, 318 experienced 469 hospitalizations for HF; of 2373 assigned to dapagliflozin, 230 patients experienced 340 admissions. In a multivariable model, factors associated with a higher risk of recurrent HF hospitalizations included higher heart rate, higher N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. In the Lei-Wei-Yang-Ying model, the rate ratio for the effect of dapagliflozin on recurrent HF hospitalizations or cardiovascular death was 0.75 (95% CI, 0.65–0.88),
P
=0.0002. In the joint frailty model, the rate ratio for total HF hospitalizations was 0.71 (95% CI, 0.61–0.82),
P
<0.0001, whereas, for cardiovascular death, the hazard ratio was 0.81 (95% CI, 0.67–0.98),
P
=0.0282.

Conclusions:
Dapagliflozin reduced the risk of total (first and repeat) HF hospitalizations and cardiovascular death. Time-to-first event analysis underestimated the benefit of dapagliflozin in HF and reduced ejection fraction.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03036124.
The Unconventional Eyewall Replacement Cycle of Hurricane Ophelia (2005)
Authors: Razin Muhammad Naufal , Bell Michael M. 
Published: April 2021

AbstractHurricane Ophelia (2005) underwent an unconventional eyewall replacement cycle (ERC) as it was a Category 1 storm located over cold sea surface temperatures near 23°C. The ERC was analyzed using airborne radar, flight-level, and dropsonde data collected during the Hurricane Rainband and Intensity Change Experiment (RAINEX) intensive observation period on 11 September 2005. Results showed that the spin-up of the secondary tangential wind maximum during the ERC can be attributed to the efficient convergence of absolute angular momentum by the mid-level inflow of Ophelia’s dominantly stratiform rainbands. This secondary tangential wind maximum strongly contributed to the azimuthal mean tangential wind field, which is conducive for increased low-level supergradient winds and corresponding outflow. The low-level supergradient forcing enhanced convergence to form a secondary eyewall. Ophelia provides a unique example of an ERC occurring in a weaker storm with predominantly stratiform rainbands, suggesting an important role of stratiform precipitation processes in the development of secondary eyewalls.
Postoperative Infection Rate and Associated Factors Following Endoscopic Sinus Surgery
Authors: Shah Sharan J. , Hawn Vivian S. , Zhu Nina , Fang Christina H. , Gao Qi , Akbar Nadeem A. , Abuzeid Waleed M. 
Published: April 2021

Objectives: There is a paucity of data on postoperative infections after endoscopic sinus surgery and associated risk factors. Our objective was to evaluate a cohort of patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis to determine which perioperative factors may be associated with infection in the 30-day postoperative period. Methods: A retrospective cohort study of adults who underwent ESS at a tertiary academic medical center from 2015 to 2018 was performed. The primary outcome was incidence of postoperative infection, defined by identification of sinus purulence on nasal endoscopy necessitating antibiotics within 30 days of surgery. Independent variables collated included the result of postoperative cultures and use of perioperative antibiotics, oral corticosteroids, packing, and steroid-eluting stents. Statistical analysis involved bivariate analysis to identify variables that correlated with postoperative infection and subsequent multivariate logistic regression to identify independent risk factors. Results: Three hundred seventy-eight unique ESS cases performed in 356 patients were reviewed. The mean age was 46 years (range, 18-87). The most common indication for surgery was chronic rhinosinusitis without nasal polyposis. The postoperative infection rate was 10.1%. The most commonly cultured pathogen was Staphylococcus aureus. Multivariate logistic regression analysis showed that postoperative systemic corticosteroid use was the only risk factor independently associated with infection (OR 3.47 [95% CI 1.23-9.76], P = .018). Conclusion: The incidence of postoperative infection following ESS was 10.1%. The use of postoperative systemic corticosteroids independently increased the risk of infection by 3.47-fold.
One-year real life data of our patients with moderate-severe Crohn’s disease who underwent ustekinumab therapy
Authors: Bacaksız Ferhat , Arı Derya , Gökbulut Volkan , Öztürk Ömer , Kayaçetin Ertuğrul 
Published: April 2021

Aim The aim of this study was to present one-year real-life data of our patients with CD who showed unresponsiveness and/or intolerance to biological agents and then received ustekinumab treatment through an early access program. Materials and methods The retrospective study reviewed the 52-week clinical data of 10 patients with moderate or severe CD who underwent ustekinumab therapy. Results The 10 patients comprised 7 (70%) men and 3 (30%) women with a mean age of 38 ± 11.3 years. Mean disease duration was 13.5 ± 8.5 years. Mean pretreatment CDAI score was 273.5 ± 92 and mean pretreatment HBI score was 11.6 ± 3.8. At the end of the 8-week intravenous induction treatment, 5 (55%) patients showed clinical remission according to the CDAI and HBI scores. Additionally, 62.5% of the patients were in clinical remission at the end of week 52 according to the CDAI and HBI scores. No drug-related side effects were observed in any patient throughout the treatment. Conclusion Ustekinumab appears to be effective and safe in the treatment of moderate and severe CD, particularly in cases of unresponsiveness and intolerance to biological agents such as anti-TNF, and in the achievement of clinical remission.
Ophthalmologic manifestations of adult patients with cystic fibrosis
Authors: Giannakouras Panagiotis , Kanakis Menelaos , Diamantea Filia , Tzetis Maria , Koutsandrea Chrysanthi , Papaconstantinou Dimitrios , Georgalas Ilias 
Published: April 2021

Introduction: Cystic fibrosis (CF) is the most common life-shortening recessive genetic disease in Caucasians, affecting primarily the lungs. The objective of our study was to investigate potential ophthalmologic involvement in adult patients with CF. Methods: Fifty adult patients with cystic fibrosis and 60 age- and sex-matched controls underwent complete ophthalmologic examination including tear-film Break-Up Time (BUT), Macular Thickness, and peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness measurements using Spectral Domain-OCT. Results: CF patients had significantly lower nasal-inferior pRNFL thickness (median 82 IQR 67–102 vs 92.5 IQR 82–107, p = 0.005) and lower percentage of normal tear Break-Up Time (56.0% vs 96.7%, p = 0.001) than healthy controls. All CF patients with BUT <10 s were diagnosed with blepharitis at the time of our assessement. The subgroup of patients homozygous for the most common CF mutation, F508del, had lower nasal-inferior pRNFL thickness ( p = 0.014) and lower percentage of normal tear Break-Up Time ( p = 0.001) compared to the control group. Additional findings, present in the CF group only, were punctuate retinal hemorrhages (four patients), vessel tortuosity (four patients), snail-track degeneration, and retinal tufts (two patients without refractive error). There were no significant differences in visual acuity, refractive errors, gonioscopic findings, or intraocular pressure between the groups. Conclusions: Our study is, to the best of our knowledge, the largest ophthalmologic study of patients with cystic fibrosis. We found that CF patients had significantly decreased inferior-quadrant peripapillary retinal nerve fiber layer thickness and decreased tear-film break-up time compared to controls. We highlight the importance of careful regular ophthalmologic assessment and follow-up of these patients.
Drivers of Cost in Primary Single-Level Lumbar Fusion Surgery
Authors: Hwang Raymond W. , Golenbock Samuel W. , Kim David H. 
Published: April 2021

Study Design: Retrospective cohort. Objectives: Allocating cost is challenging with traditional hospital accounting. Time-driven activity-based costing (TDABC) is an efficient method to accurately assign cost. We sought to characterize the variation in direct total hospital cost (THC) among both lumbar fusion approaches and surgeons. Methods: Patients were treated with single-level anterior interbody (ALIF), lateral interbody (LLIF), transforaminal interbody (TLIF), instrumented posterolateral (PLF) or in-situ fusion (ISF) for degenerative disease. Process maps were developed for preoperative, intraoperative and postoperative care. THC was composed of implant, medication, other supply, and personnel costs. Linear regression and descriptive statistics were used to analyze THC variation. Results: A total of 696 patients underwent surgery by 8 surgeons. Approximately 50% of THC variation was associated with procedure choice while patient characteristics explained 10%. Implants (including biologics) accounted for 45% of cost. With reference to PLF, THC ranged from 0.6x (ISF) to 1.7x (LLIF). Implant cost ranged from 2.5x reference (LLIF) to 0.1x (ISF). There was a 1.7x difference between the highest THC surgeon and the lowest. The fusion type with the highest THC variation was TLIF. The surgeon with the highest TLIF THC was 1.5x more expensive than the surgeon with the lowest. Conclusions: Surgeon-based choices have the greatest effect on THC variation and represent the largest opportunities for cost savings. Primary single-level lumbar fusion THC is driven primarily by fusion type. Implants, including biologics, account for nearly half this cost. Future work should incorporate outcomes data to characterize the differential value conferred by higher THC fusions.
Association between apolipoprotein gene polymorphisms and hyperlipidemia: a meta-analysis
Authors: Zhao Xiao-Ning , Sun Quan , Cao You-Qin , Ran Xiao , Cao Yu 
Published: April 2021

AbstractBackgroundHyperlipidemia plays an important role in the etiology of cardio-cerebrovascular disease. Over recent years, a number of studies have explored the impact of apolipoprotein genetic polymorphisms in hyperlipidemia, but considerable differences and uncertainty have been found in their association with different populations from different regions.ResultsA total of 59 articles were included, containing in total 13,843 hyperlipidemia patients in the case group and 15,398 healthy controls in the control group. Meta-analysis of the data indicated that APOA5–1131 T > C, APOA1 -75 bp, APOB XbaI, and APOE gene polymorphisms were significantly associated with hyperlipidemia, with OR values of 1.996, 1.228, 1.444, and 1.710, respectively. AllP-values were less than 0.05.ConclusionsMeta-analysis of the data indicated that the C allele of APOA5 1131 T > C, the A allele at APOA1-75 bp, the APOB XbaI T allele, and the ε2 and ε4 allele of APOE were each a risk factor for susceptibility for hyperlipidemia.
Effect of quadratus lumborum block on postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial
Authors: Zhu Manhua , Qi Yong , He Huijuan , Zhang Song , Mei Yuliu 
Published: April 2021

AbstractBackgroundQuadratus lumborum block (QLB) is a novel and effective postoperative analgesia method for abdominal surgeries. However, whether QLB can affect early postoperative cognitive function by inhibiting surgical traumatic stress and the inflammatory response remains unclear. This study aimed to explore the effect of QLB on postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy.MethodsSixty-four elderly patients who underwent laparoscopic radical gastrectomy were randomly divided into the QLB group (Q group,n = 32) and control group (C group,n = 32). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to measure cognitive function 1 day before and 7 days after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decline of ≥ 1 SD in both tests. The visual analog scale (VAS) scores 6 h (T1), 24 h (T2), and 48 h (T3) after surgery were measured. The serum levels of high mobility group box protein 1 (HMGB1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated 1 day before surgery (baseline), and 1 day (day 1) and 3 days after surgery (day 3). The intraoperative remifentanil dosage, sufentanil consumption 24 h after surgery, recovery time from anesthesia, and adverse effects were also compared.ResultsPOCD was present in two patients in the QLB group and eight patients in the C group 7 days after surgery (6.7 % vs. 27.6 %,P = 0.032). The MMSE and MoCA scores were similar in both groups preoperatively, and the two scores were higher in the QLB group than in the C group 7 days after surgery (P < 0.05). The VAS scores were significantly lower in the Q group at all times after surgery (P < 0.05). Compared with the C group, the levels of HMGB1, TNF-α, and IL-6 were significantly decreased 1 and 3 days after surgery in the QLB group (P < 0.05). The remifentanil consumption intraoperatively and sufentanil 24 h postoperatively were significantly lower in the QLB group (P < 0.05). The recovery time from anesthesia was shorter in the QLB group (P < 0.05). No severe adverse effects occurred in either group.ConclusionsQLB could improve postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy. This may be related to the suppression of the inflammatory response after surgery.Trial registrationChictr.org.cnidentifier ChiCTR1900027574 (Date of registry: 19/11/2019, prospectively registered).
The effects of vitamin E supplementation on malondialdehyde as a biomarker of oxidative stress in haemodialysis patients: a systematic review and meta-analysis
Authors: Bergin Peter , Leggett Aoife , Cardwell Chris R. , Woodside Jayne V. , Thakkinstian Ammarin , Maxwell Alexander P. , McKay Gareth J. 
Published: April 2021

AbstractBackgroundHaemodialysis (HD) patients tend to have higher levels of oxidative stress (OS), associated with increased morbidity and premature mortality, compared to the general population. Levels of malondialdehyde (MDA), a biomarker of OS, are reduced by the antioxidant properties of vitamin E (VE) but outcomes from randomised control trials of VE supplementation on MDA in HD patients have been inconsistent.MethodsWe undertook a systematic review and meta-analysis of adult HD patients from VE supplementation studies with measures of MDA. The following search criteria of MEDLINE and EMBASE were considered from inception to January 2020: ‘dialysis’ AND ‘Vitamin E OR tocopherol’ AND ‘malondialdehyde OR MDA’. Two reviewers independently extracted study data and assessed risk of bias. Mean MDA levels and standard deviation were determined before and after VE supplementation. Standardised mean difference (SMD) and standard error were calculated as the within person difference and units of measure were not consistently recorded across all studies. The SMD were pooled using random effects meta-analysis.ResultsThe SMD of MDA levels from 18 comparisons was significantly lower in HD patients following VE supplementation (− 1.55; confidence interval: − 2.17 to − 0.94,P < 0.00001). There were significant levels of heterogeneity between studies (I2value = 91%; P < 0.00001) with evidence of potential publication bias toward smaller studies.ConclusionsOur findings support the use of VE to reduce the effects of OS in HD patients although high levels of heterogeneity and variation in the methodological approaches used by some studies highlight the need for further investigation.