bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation on Reinforcement Effects of Nanocellulose on the Mechanical Properties, Water Absorption Capacity, Biodegradability, Optical Properties, and Thermal Stability of a Polyvinyl Alcohol Nanocomposite Film
Authors: Bacha Ebise Getacho , Demsash Hundessa Dessalegn , Shumi Lema Deme , Debesa Bune Erre 
Published: June 2022

This paper presents the reinforcement of nanocellulose (NC) in polyvinyl alcohol (PVA) to examine the effect of the amount of reinforcement on the properties of PVA. The nanocellulose was successfully extracted by sulfuric acid hydrolysis method and ultrasonication, and successively reinforced with polyvinyl alcohol by the solvent-casting method. After incorporating nanocellulose into the PVA matrix, the effect of nanocellulose on the tensile strength, elongation at break, water absorption capacity, transmittance, thermal stability, and biodegradability of PVA was investigated. The tensile strength increased from

24.5
±
0.53

MPa

to

35.5
±
0.55

MPa

and

40.6
±
0.73

MPa

with the addition of 2%NC and 5%NC, respectively. The elongation at break increased from

40
±
0.53
%

to

45.7
±
0.53
%

with 2%NC, and after the reinforcement of 7%NC, it decreased to

32.2
±
0.75
%

. The water absorption capacity result reveals that neat PVA absorbs the highest amount of water which is

84.6
±
0.56
%

and is reduced to

73
±
0.78
%

by adding 2%NC. By increasing the nanocellulose loading to 7%, the water intake capacity was reduced to

61
±
0.59
%

which illustrates the water intake was reduced linearly with the increment of NC. The ultraviolet-visible (UV-Vis) result implies that the transmittance of neat PVA and PVA-2%NC composite film was 85.4% and 78.2% at 600 nm, respectively, which indicates the decrement in transmittance. The thermogravimetry analysis (TGA) reveals that the thermal stability of polyvinyl alcohol after incorporating nanocellulose particles was reduced. The weight loss of neat PVA is

70.7
±
1.7
%

after 90 days while the weight loss of the PVA composite films reinforced with 1%, 3%, 5%, 7%, and 9% was

65
±
1.85
%

,

57
±
1.57
%

,

55.6
±
0.64
%

,

52
±
1.73
%

, and

53.1
±
1.72
%

, respectively. The scanning electron microscopy micrograph for the PVA-6%NC nanocomposite film reveals a dispersion of nanocellulose in a matrix.
Evaluation of the Property of Axillary Lymph Nodes and Analysis of Lymph Node Metastasis Factors in Breast Cancer by Ultrasound Elastography
Authors: Zhou Jia , Zhang Qingyu , Zhang Qi , Yan Lei , Gao Qing 
Published: June 2022

This research was aimed at investigating the role of ultrasound elastography (UE) in evaluating the properties of axillary lymph nodes in breast cancer and exploring the influencing factors of lymph node metastasis in breast cancer patients. Routine ultrasonography (US) and UE were performed for 160 breast cancer patients. 80 cases were in the group with lymph node metastasis, and the other 80 were in the nonlymph node metastasis group. The sensitivity, specificity, and accuracy of the two ultrasound examinations were compared, the receiver-operator characteristic (ROC) curves were drawn, and the influencing factors of lymph node metastasis were analyzed. The sensitivity, specificity, and accuracy of UE in diagnosing axillary lymph nodes of breast cancer were 97.22%, 95.45%, and 96.25%, respectively, which were markedly higher than those of routine US (

P
<
0.05

). Cortical thickness, blood flow grade, blood flow type, and elasticity score had a greater impact on axillary lymph node metastasis of breast cancer. When

cortical

thickness
≥
3

cm

, blood flow was of 2-3 grades, blood flow was the peripheral/mixed type, and elasticity score was 3-4 points, these became risk factors for lymph node metastasis in breast cancer patients. UE was effective in diagnosing the property of lymph nodes and could evaluate lymph node metastasis in breast cancer patients. It had a good clinical value and was worthy of popularization and application.
Selective Vulnerability of Senescent Glioblastoma Cells to BCL-XL Inhibition
Authors: Rahman Masum , Olson Ian , Mansour Moustafa , Carlstrom Lucas P. , Sutiwisesak Rujapope , Saber Rehan , Rajani Karishma , Warrington Arthur E. , Howard Adam , Schroeder Mark , Chen Sisi , Decker Paul A. , Sananikone Eliot F. , Zhu Yi , Tchkonia Tamar , Parney Ian F. , Burma Sandeep , Brown Desmond , Rodriguez Moses , Sarkaria Jann N. , Kirkland James L. , Burns Terry C. 
Published: June 2022

Abstract

Glioblastoma (GBM) is a rapidly fatal malignancy typically treated with radiation and temozolomide (TMZ), an alkylating chemotherapeutic. These cytotoxic therapies cause oxidative stress and DNA damage, yielding a senescent-like state of replicative arrest in surviving tumor cells. Unfortunately, recurrence is inevitable and may be driven by surviving tumor cells eventually escaping senescence. A growing number of so-called “senolytic” drugs have been recently identified that are defined by their ability to selectively eliminate senescent cells. A growing inventory of senolytic drugs is under consideration for several diseases associated with aging, inflammation, DNA damage, as well as cancer. Ablation of senescent tumor cells after radiation and chemotherapy could help mitigate recurrence by decreasing the burden of residual tumor cells at risk of recurrence. This strategy has not been previously explored for GBM. We evaluated a panel of 10 previously described senolytic drugs to determine whether any could exhibit selective activity against human GBM persisting after exposure to radiation or TMZ. Three of the 10 drugs have known activity against BCL-XL and preferentially induced apoptosis in radiated or TMZ-treated glioma. This senolytic activity was observed in 12 of 12 human GBM cell lines. Efficacy could not be replicated with BCL-2 inhibition or senolytic agents acting against other putative senolytic targets. Knockdown of BCL-XL decreased survival of radiated GBM cells, whereas knockdown of BCL-2 or BCL-W yielded no senolytic effect.

Implications:
These findings imply that molecularly heterogeneous GBM lines share selective senescence-induced BCL-XL dependency increase the significance and translational relevance of the senolytic therapy for latent glioma.
Vitamin D Receptor Activation Attenuates Hippo Pathway Effectors and Cell Survival in Metastatic Neuroblastoma
Authors: Ladumor Yagnesh , Seong Bo Kyung Alex , Hallett Robin , Valencia-Sama Ivette , Adderley Teresa , Wang Yingying , Kee Lynn , Gont Alexander , Kaplan David R. , Irwin Meredith S. 
Published: June 2022

Abstract

Survival for high-risk neuroblastoma remains poor. Most patients who recur, present with metastatic disease, and few targetable pathways that govern spread to distant sites are currently known. We previously developed a metastatic mouse model to select cells with enhanced ability to spread to the bone and brain and identified a signature based on differentially expressed genes, which also predicted patient survival. To discover new neuroblastoma therapies, we utilized the Connectivity Map to identify compounds that can reverse this metastatic transcriptional signature and found calcipotriol, a vitamin D3 analog, to be a compound that selectively targets cell lines with enhanced metastatic potential. Calcipotriol treatment of enhanced metastatic, but not parental, cells reduces proliferation and survival via vitamin D receptor (VDR) signaling, increases the expression of RASSF2, a negative regulator of the Hippo signaling pathway, and reduces the levels of the Hippo pathway effectors YAP and TAZ. RASSF2 is required for the effects of calcipotriol and for the reduction of levels and nuclear localization of YAP/TAZ. Migration of the enhanced metastatic cells and YAP/TAZ levels are reduced after calcipotriol treatment and YAP overexpression reduces calcipotriol sensitivity. Furthermore, metastatic cells that overexpress VDR also showed lower tumor burden in vivo.

Implications:
This newly identified link between VDR signaling and the Hippo pathway could inform treatment strategies for metastatic neuroblastoma.
Inhibiting WEE1 and IKK-RELA Crosstalk Overcomes TNFα Resistance in Head and Neck Cancers
Authors: Hu Zhengbo , Viswanathan Ramya , Cheng Hui , Chen Jianghong , Yang Xinping , Huynh Angel , Clavijo Paul , An Yi , Robbins Yvette , Silvin Christopher , Allen Clint , Ormanoglu Pinar , Martin Scott , Cornelius Shaleeka , Saleh Anthony , Chen Zhong , Van Waes Carter , Morgan Ethan L. 
Published: June 2022

AbstractTNFα is a key mediator of immune and radiotherapy-induced cytotoxicity, but many cancers, including head and neck squamous cell carcinomas (HNSCC), display TNF resistance due to activation of the canonical IKK–NF-κB/RELA pro-survival pathway. However, toxicities associated with direct targeting of the canonical pathway point to the need to identify mechanism(s) contributing to TNFα resistance and synthetic lethal targets to overcome such resistance in cancer cells. Here, RNAi screening for modulators of TNFα–NF-κB reporter activity and cell survival unexpectedly implicated the WEE1 and CDC2 G2–M checkpoint kinases. The IKKα/β-RELA and WEE1-CDC2 signaling pathways are activated by TNFα and form a complex in cell lines derived from both human papillomavirus (−) and (+) subtypes of HNSCC. WEE1 inhibitor AZD1775 reduced IKK/RELA phosphorylation and the expression of NF-κB–dependent pro-survival proteins Cyclin D1 and BCL2. Combination of TNFα and AZD1775 enhanced caspase-mediated apoptosis in vitro, and combination treatment with radiotherapy and AZD1775 potentiated inhibition of HNSCC tumor xenograft growth in vivo, which could be significantly attenuated by TNFα depletion. These data offer new insight into the interplay between NF-κB signaling and WEE1-mediated regulation of the G2–M cell-cycle checkpoint in HNSCC.Implications:Inhibiting WEE1 and IKK-RELA crosstalk could potentially enhance the effects of therapies mediated by TNFα with less systemic immune suppression and toxicity than observed with direct interruption of IKK-NF-κB/RELA signaling.
Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice
Authors: Tsuruta Akito , Shiiba Yuki , Matsunaga Naoya , Fujimoto Marina , Yoshida Yuya , Koyanagi Satoru , Ohdo Shigehiro 
Published: June 2022

Abstract

Cancer cells have acquired several pathways to escape from host immunity in the tumor microenvironment. Programmed death 1 (PD-1) receptor and its ligand PD-L1 are involved in the key pathway of tumor immune escape, and immune checkpoint therapy targeting PD-1 and PD-L1 has been approved for the treatment of patients with certain types of malignancies. Although PD-1 is a well-characterized receptor on T cells, the immune checkpoint receptor is also expressed on tumor-associated macrophages (TAM), a major immune component of the tumor microenvironment. In this study, we found significant diurnal oscillation in the number of PD-1–expressing TAMs collected from B16/BL6 melanoma-bearing mice. The levels of Pdcd1 mRNA, encoding PD-1, in TAMs also fluctuated in a diurnal manner. Luciferase reporter and bioluminescence imaging analyses revealed that a NF-κB response element in the upstream region of the Pdcd1 gene is responsible for its diurnal expression. A circadian regulatory component, DEC2, whose expression in TAMs exhibited diurnal oscillation, periodically suppressed NF-κB–induced transactivation of the Pdcd1 gene, resulting in diurnal expression of PD-1 in TAMs. Furthermore, the antitumor efficacy of BMS-1, a small molecule inhibitor of PD-1/PD-L1, was enhanced by administering it at the time of day when PD-1 expression increased on TAMs. These findings suggest that identification of the diurnal expression of PD-1 on TAMs is useful for selecting the most appropriate time of day to administer PD-1/PD-L1 inhibitors.

Implications:
Selecting the most appropriate dosing time of PD-1/PD-L1 inhibitors may aid in developing cancer immunotherapy with higher efficacy.
EML4-ALK Variant 3 Promotes Mitotic Errors and Spindle Assembly Checkpoint Deficiency Leading to Increased Microtubule Poison Sensitivity
Authors: Lucken Kellie , O'Regan Laura , Choi Jene , Sampson Josephina , Pashley Sarah L. , Bayliss Richard , Khan Sam , Fry Andrew M. 
Published: June 2022

Abstract

EML4-ALK is an oncogenic fusion protein present in approximately 5% of non–small cell lung cancers (NSCLC). Alternative breakpoints in the gene encoding EML4 result in distinct variants that are linked to markedly different patient outcomes. Patients with EML4-ALK variant 3 (V3) respond poorly to ALK inhibitors and have lower survival rates compared with patients with other common variants, such as V1. Here, we use isogenic Beas-2B bronchial epithelial cell lines expressing EML4-ALK V1 or V3, as well as ALK-positive NSCLC patient cells that express V1 (H3122 cells) or V3 (H2228 cells), to show that EML4-ALK V3 but not V1 leads to hyperstabilized K-fibers in mitosis, as well as errors in chromosome congression and segregation. This is consistent with our observation that EML4-ALK V3 but not V1 localizes to spindle microtubules and that wild-type EML4 is a microtubule stabilizing protein. In addition, cells expressing EML4-ALK V3 exhibit loss of spindle assembly checkpoint control that is at least in part dependent on ALK catalytic activity. Finally, we demonstrate that cells expressing EML4-ALK V3 have increased sensitivity to microtubule poisons that interfere with mitotic spindle assembly, whereas combination treatment with paclitaxel and clinically approved ALK inhibitors leads to a synergistic response in terms of reduced survival of H2228 cells.

Implications:
This study suggests that combining the microtubule poison, paclitaxel, with targeted ALK inhibitors may provide an effective new treatment option for patients with NSCLC with tumors that express the EML4-ALK V3 oncogenic fusion.
Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial
Authors: Del Brutto Victor J. , Diener Han‐Christoph , Easton J. Donald , Granger Christopher B. , Cronin Lisa , Kleine Eva , Grauer Claudia , Brueckmann Martina , Toyoda Kazunori , Schellinger Peter D. , Lyrer Philippe , Molina Carlos A. , Chutinet Aurauma , Bladin Christopher F. , Estol Conrado J. , Sacco Ralph L. 
Published: June 2022

Background
We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS).

Methods and Results

We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23–2.32]), male sex (HR, 1.60 [95% CI, 1.27–2.02]), and CHA
2
DS
2
‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA
2
DS
2
‐VASc of 2 to 3, were independent predictors for recurrent stroke.

Conclusions
In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02239120.
Intervention Adherence in REHAB‐HF: Predictors and Relationship With Physical Function, Quality of Life, and Clinical Events
Authors: Nelson M. Benjamin , Gilbert Olivia N. , Duncan Pamela W. , Kitzman Dalane W. , Reeves Gordon R. , Whellan David J. , Mentz Robert J. , Chen Haiying , Hewston Leigh Ann , Taylor Karen M. , Pastva Amy M. 
Published: June 2022

Background
The REHAB‐HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial showed that a novel, early, transitional, tailored, progressive, multidomain physical rehabilitation intervention improved physical function and quality of life in older, frail patients hospitalized for acute decompensated heart failure. This analysis examined the relationship between intervention adherence and outcomes.

Methods and Results

Adherence was defined as percent of sessions attended and percent of sessions attended adjusted for missed sessions for medical reasons. Baseline characteristics were examined to identify predictors of session attendance. Associations of session attendance with change in physical function (Short Physical Performance Battery [primary outcome], 6‐minute walk distance, quality of life [Kansas City Cardiomyopathy Questionnaire], depression, and clinical events [landmarked postintervention]) were examined in multivariate analyses. Adherence was 67%±34%, and adherence adjusted for missed sessions for medical reasons was 78%±34%. Independent predictors of higher session attendance were the following: nonsmoking, absence of myocardial infarction history and depression, and higher baseline Short Physical Performance Battery. After adjustment for predictors, adherence was significantly associated with larger increases in Short Physical Performance Battery (parameter estimate: β=0.06[0.03–0.10],
P
=0.001), 6‐minute walk distance (β=1.8[0.2–3.5],
P
=0.032), and Kansas City Cardiomyopathy Questionnaire score (β=0.62[0.26–0.98],
P
=0.001), and reduction in depression (β=−0.08[−0.12 to 0.04],
P
<0.001). Additionally, higher adherence was significantly associated with reduced 6‐month all‐cause rehospitalization (rate ratio: 0.97 [0.95–0.99],
P
=0.020), combined all‐cause rehospitalization and death (0.97 [0.95–0.99],
P
=0.017), and all‐cause rehospitalization days (0.96 [0.94–0.99],
P
=0.004) postintervention.

Conclusions
In older, frail patients with acute decompensated heart failure, higher adherence was significantly associated with improved patient‐centered and clinical event outcomes. These data support the efficacy of the comprehensive adherence plan and the subsequent intervention‐related benefits observed in REHAB‐HF.

Registration

URL:
https://clinicaltrials.gov/
; Unique identifier: NCT02196038.
Subcutaneous Versus Transvenous Implantable Defibrillator Therapy: A Systematic Review and Meta‐Analysis of Randomized Trials and Propensity Score–Matched Studies
Authors: Fong Khi Yung , Ng Colin Jun Rong , Wang Yue , Yeo Colin , Tan Vern Hsen 
Published: June 2022

Background
Subcutaneous implantable cardioverter‐defibrillators (S‐ICDs) have been of great interest as an alternative to transvenous implantable cardioverter‐defibrillators (TV‐ICDs). No meta‐analyses synthesizing data from high‐quality studies have yet been published.

Methods and Results

An electronic literature search was conducted to retrieve randomized controlled trials or propensity score–matched studies comparing S‐ICD against TV‐ICD in patients with an implantable cardioverter‐defibrillator indication. The primary outcomes were device‐related complications and lead‐related complications. Secondary outcomes were inappropriate shocks, appropriate shock, all‐cause mortality, and infection. All outcomes were pooled under random‐effects meta‐analyses and reported as risk ratios (RRs) and 95% CIs. Kaplan–Meier curves of device‐related complications were digitized to retrieve individual patient data and pooled under a 1‐stage meta‐analysis using Cox models to determine hazard ratios (HRs) of patients undergoing S‐ICD versus TV‐ICD. A total of 5 studies (2387 patients) were retrieved. S‐ICD had a similar rate of device‐related complications compared with TV‐ICD (RR, 0.59 [95% CI, 0.33–1.04];
P
=0.070), but a significantly lower lead‐related complication rate (RR, 0.14 [95% CI, 0.07–0.29];
P
<0.0001). The individual patient data–based 1‐stage stratified Cox model for device‐related complications across 4 studies yielded no significant difference (shared‐frailty HR, 0.82 [95% CI, 0.61–1.09];
P
=0.167), but visual inspection of pooled Kaplan–Meier curves suggested a divergence favoring S‐ICD. Secondary outcomes did not differ significantly between both modalities.

Conclusions
S‐ICD is clinically superior to TV‐ICD in terms of lead‐related complications while demonstrating comparable efficacy and safety. For device‐related complications, S‐ICD may be beneficial over TV‐ICD in the long term. These indicate that S‐ICD is likely a suitable substitute for TV‐ICD in patients requiring implantable cardioverter‐defibrillator implantation without a pacing indication.
Risk Burden of Coronary Perforation in Chronic Total Occlusion Recanalization: Latin American CTO Registry Analysis
Authors: Ribeiro Marcelo Harada , Campos Carlos M. , Padilla Lucio , da Silva Antonio Carlos B. , de Paula João Eduardo T. , Alcantara Marco , Santiago Ricardo , Hanna Franklin , da Silva Franciele R. , Belli Karlyse C. , Azzalini Lorenzo , de Oliveira Pedro P. , Araujo Gustavo N. , Sucato Vincenzo , Mashayekhi Kambis , Galassi Alfredo R. , Abizaid Alexandre , Quadros Alexandre 
Published: June 2022

Background
Coronary perforation is a life‐threatening complication of acute percutaneous coronary intervention (PCI) for chronic total occlusions (CTO), but data on midterm outcomes are limited.

Methods and Results

Data from LATAM (Latin American)‐CTO Registry (57 centers; 9 countries) were analyzed. We assessed the risk of 30‐day, 1‐year major adverse cardiac events of coronary perforation using time‐to‐event and weighted composite end point analysis having CTO PCI without perforation as comparators. Additionally, we studied the independent predictors of perforation in these patients. Of 2054 patients who underwent CTO PCI between 2015 and 2018, the median Multicenter CTO Registry in Japan and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention‐Chronic total occlusions scores were 2.0 (1.0–3.0) and 1.0 (0.0–2.0), respectively. The perforation rate was 3.7%, of which 55% were Ellis class 1. After 1‐year coronary perforation had higher major adverse cardiac events rates (24.9% versus 13.3%;
P
<0.01). Using weighted composite end point, perforation was associated with increased bleeding and ischemic events at 6 months (
P
=0.04) and 1 year (
P
<0.01). We found as independent predictors associated with coronary perforation during CTO PCI: maximum activated clotting time (
P
<0.01), Multicenter CTO Registry in Japan score ≥2 (
P
=0.05), antegrade knuckle wire (
P
=0.04), and right coronary artery CTO PCI (
P
=0.05).

Conclusions
Coronary perforation was infrequent and associated with anatomical and procedural complexity, resulting in higher risk of hemorrhagic and ischemic events. Landmark and weighted analysis showed a sustained burden of major events between 6 months and 1 year follow‐up.