bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Conscious Control of Scapular Orientation in Oral Cancer Survivors With Scapular Dyskinesis: A Randomized Controlled Trial
Authors: Chen Yueh-Hsia , Huang Cheng-Ya , Liang Wei-An , Lin Chi-Rung , Chao Yuan-Hung 
Published: August 2021

Objectives: Spinal accessory nerve dysfunction is one of the complications of neck dissection in patients with oral cancer. This study aimed to explore the effects of long-term scapular-focused exercises and conscious control of scapular orientation on scapular movement and quality of life (QoL). Methods: This study was a randomized controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis. Thirty-six patients with oral cancer were randomly allocated to the motor-control group (scapular-focused exercise + conscious control of scapular orientation) or the regular-exercise group (scapular-focused exercises only). Both groups received conventional physical therapy after neck dissection for 3 months. Shoulder pain intensity, active range of motion (AROM) of shoulder abduction, scapular muscle strength and activity under maximal voluntary isometric contraction (MVIC), scapular muscle activity when performing scapular movements, and QoL were measured at baseline, 1 month after the start of the intervention, and the end of the intervention. Results: Both groups showed significant improvement in all outcomes except shoulder pain intensity. After the 3-month intervention, the motor-control group had more significant improvement in AROM of shoulder abduction with a 19° difference (95% CI: 10-29, P < .001), muscle strength of upper trapezius with an 11 N difference (95% CI: 2-20; P = .021), and QoL than the regular-exercise group. When performing shoulder horizontal adduction and flexion, the relative value (%MVIC) of serratus anterior was smaller in the motor-control group with a 106%MVIC difference (95% CI: 7-205, P = .037). Conclusions: Scapular-focused exercises have promising effects on spinal accessory nerve dysfunction. Combining scapular-focused exercises with conscious control of scapular orientation has more remarkable benefits on AROM of shoulder abduction, UT muscle strength, and muscle activation pattern than the scapular-focused exercises alone. Conscious control of scapular orientation should be considered to integrate into scapular-focused exercises in patients with oral cancer and scapular dyskinesis. Trial registry name and URL, and registration number: ClinicalTrials.gov (URL: https://clinicaltrials.gov ; Approval No: NCT03545100)
Exploring attitudes towards use of technology to support stroke survivors living at home: A quantitative and qualitative content analysis study in Spain
Authors: Ortiz-Fernandez Leire , Magnusson Charlotte , Ruiz Agustin Gutierrez , Indart Lorea Martinez , Zabala Joana Sagastagoya , Menica Juan Andres Alava , Arri Eunate Arana 
Published: August 2021

Purpose The aim of this study was to better understand the attitudes towards the use of technology to support chronic stroke survivors in a home-based setting. Methods A quantitative study was used on the data obtained from a face to face survey with the sample group, incorporating quantitative statistical analysis. Results Participants reported positive attitudes towards using technology for their own independent health management. The purpose of the home-based technology was different: source of information, supporting self-management, pharmacological treatment reminders… and differed according to age, educational level and survivor disability. Installing devices and sharing information remains a challenge. Conclusions 100% of stroke survivors living in the community with any type of disability, reported that they would like to use technology as a tool to help improve their health status.
A Surgical Algorithm According to Pivot-Shift Grade in Patients With ACL Injury: A Prospective Clinical and Radiological Evaluation
Authors: Akmese Ramazan , Ovali Sancar Alp , Celebi Mehmet Mesut , Malatyali Batu , Kocaoglu Hakan 
Published: August 2021

Background: Some patients have a positive pivot-shift finding and rotational instability after anterior cruciate ligament (ACL) reconstruction (ACLR). Three major pathologies known to affect the pivot-shift examination include ACL tear, anterolateral ligament injury, and loss of posterior lateral meniscus root function. Purpose: To describe a surgical algorithm determining indications for lateral extra-articular tenodesis (LET) based on intraoperative pivot-shift examination to prevent postoperative pivot shift and rotational instability and to evaluate the 2-year clinical and functional outcomes. Study Design: Case series; Level of evidence, 4. Methods: The study included 47 consecutive patients (39 men and 8 women) who underwent operative treatment for ACL injury between 2016 and 2017. Pivot-shift examination was performed under anesthesia, and the pivot shift was graded as grade 1 (glide), grade 2 (clunk), or grade 3 (gross). According to the surgical algorithm, single-bundle ACLR was performed in patients with grade 1 pivot shift. In patients with grade 2 with loss of posterior lateral meniscus root function, concurrent lateral meniscal repair was performed, and in patients with grade 2 with an intact lateral meniscus posterior root, concurrent extra-articular iliotibial band tenodesis was performed. Patients with grade 3 underwent ACLR, lateral meniscal repair, and LET. Clinical and radiographic evaluations were performed. Results: The mean age was 27.2 years (range, 16-56 years). In total, 26 (55.3%) patients were evaluated as having pivot-shift grade 1; 16 (34%) patients, grade 2; and 5 (10.6%) patients, grade 3. A total of 7 (14.9%) patients underwent LET in addition to ACLR. Two of these patients had pivot-shift grade 2, and LET was performed since the lateral meniscus posterior root was intact. In 14 of 16 patients with grade 2, lateral meniscus root disruption was detected, and lateral meniscal repair was performed. One patient was excluded from the further follow-up because of graft failure. At a mean postoperative follow-up of 29 months in 46 patients, the pivot-shift examination was negative in all patients. The mean Lysholm and International Knee Documentation Committee subjective scores were 95.35 ± 4.40 and 82.87 ± 9.36, respectively. Radiographic evidence of osteoarthritis was not detected. Conclusion: Only 14.9% of patients needed LET. With proper ACL, lateral meniscal, and anterolateral ligament surgery, it was possible to prevent positive pivot-shift findings postoperatively.
Prognostic Impact of the Presence of Barrett’s Esophagus and Intestinal Metaplasia on Esophageal Adenocarcinoma Survival
Authors: Kolb Jennifer M. , Fox Charlie , Friedman Chloe , Scott Frank I. , Han Samuel , Marsh Megan , McCarter Martin , Kaplan Jeffrey , Lieu Christopher H. , Gleisner Ana , Katzka David A. , Wani Sachin 
Published: August 2021

Background/Aims: Barrett’s esophagus (BE), defined by the presence of intestinal metaplasia (IM) on histology, is thought to be the only identifiable precursor lesion for esophageal adenocarcinoma (EAC). Recent studies have suggested the possibility of an alternate, non-IM associated EAC that is a more aggressive form of EAC with worse survival. Among EAC patients, we aimed to compare survival of patients with and without IM at the time of diagnosis. Methods: This was a retrospective cohort study of all patients with histologic confirmed EAC evaluated at a tertiary care center from 2013 to 2019. Cases were categorized according to the presence or absence of IM on histologic specimens (Group I—IM-EAC and Group II—non-IM-EAC). We compared demographic characteristics, clinical stage, therapy, and survival between the 2 groups using the Chi-square and ANOVA tests (for categorical and continuous variables, respectively). We used Cox proportional hazards regression to determine the association of IM with overall survival, adjusting for sex, age at diagnosis, tumor location, histologic grade, and clinical stage. Results: A total of 475 patients were included in this analysis (mean age 64.8 years [SD 10.8], 89% white) and 109 (23.0%) had no evidence of IM. Compared with IM-EAC (Group I), individuals in the non-IM-EAC group were younger ( P = .01) and had a greater proportion of patients diagnosed with advanced disease (49.5 vs 20.2% for stage 4, P < .001). These patients were less likely to undergo endoscopic therapy alone (0.92% vs 29.78%, P < .001) or surgery alone (0 vs 9.84%, P = .001). On multivariable analysis, the presence of IM-EAC was associated with improved overall survival compared to non-IM-EAC (HR 0.69, 95% CI 0.49-0.96). Additional factors associated with poor survival was increasing stage of diagnosis (HR 6.49: 95% CI 3.77-11.15 for stage 4, HR 2.19: 95% CI 1.25-3.84 for stage 3, HR 2.04: 95% CI 0.98-4.25 for stage 2 compared to stage 1) and more advanced histologic stage (HR 2.00, 95% CI 1.26-3.19) for poorly/undifferentiated compared to well differentiated). Conclusions: EAC without the presence of IM on histology was associated with worse survival compared to those with IM. Future prospective studies with detailed molecular sequencing are required to clarify if 2 separate phenotypes of EAC exist (IM-EAC and non-IM-EAC). If confirmed, this may have significant implications for screening and management strategies.
Complement and the prothrombotic state
Authors: Schmidt Christoph Q. , Schrezenmeier Hubert , Kavanagh David 
Published: August 2021

AbstractIn 2007 and 2009, the regulatory approval of the first-in-class complement inhibitor eculizumab revolutionized the clinical management of 2 rare, life-threatening clinical conditions: paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Although being completely distinct diseases affecting blood cells and the glomerulus, PNH and aHUS remarkably share several features in their etiology and clinical presentation. An imbalance between complement activation and regulation at host surfaces underlies both diseases precipitating in severe thrombotic events that are largely resistant to anticoagulant and/or antiplatelet therapies. Inhibition of the common terminal complement pathway by eculizumab prevents the frequently occurring thrombotic events responsible for the high mortality and morbidity observed in patients not treated with anticomplement therapy. Although many in vitro and ex vivo studies elaborate numerous different molecular interactions between complement activation products and hemostasis, this review focuses on the clinical evidence that links these 2 fields in humans. Several noninfectious conditions with known complement involvement are scrutinized for common patterns concerning a prothrombotic statues and the occurrence of certain complement activation levels. Next to PNH and aHUS, germline-encoded CD59 or CD55 deficiency (the latter causing the disease complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy), autoimmune hemolytic anemia, (catastrophic) antiphospholipid syndrome, and C3 glomerulopathy are considered. Parallels and distinct features among these conditions are discussed against the background of thrombosis, complement activation, and potential complement diagnostic and therapeutic avenues.
Biomaterial and cellular implants: foreign surfaces where immunity and coagulation meet
Authors: Kizhakkedathu Jayachandran N. , Conway Edward M. 
Published: August 2021

Abstract
Exposure of blood to a foreign surface in the form of a diagnostic or therapeutic biomaterial device or implanted cells or tissue elicits an immediate, evolutionarily conserved thromboinflammatory response from the host. Primarily designed to protect against invading organisms after an injury, this innate response features instantaneous activation of several blood-borne, highly interactive, well-orchestrated cascades and cellular events that limit bleeding, destroy and eliminate the foreign substance or cells, and promote healing and a return to homeostasis via delicately balanced regenerative processes. In the setting of blood-contacting synthetic or natural biomaterials and implantation of foreign cells or tissues, innate responses are robust, albeit highly context specific. Unfortunately, they tend to be less than adequately regulated by the host’s natural anticoagulant or anti-inflammatory pathways, thereby jeopardizing the functional integrity of the device, as well as the health of the host. Strategies to achieve biocompatibility with a sustained return to homeostasis, particularly while the device remains in situ and functional, continue to elude scientists and clinicians. In this review, some of the complex mechanisms by which biomaterials and cellular transplants provide a “hub” for activation and amplification of coagulation and immunity, thromboinflammation, are discussed, with a view toward the development of innovative means of overcoming the innate challenges.
The ROR1 antibody-drug conjugate huXBR1-402-G5-PNU effectively targets ROR1+ leukemia
Authors: Hu Eileen Y. , Do Priscilla , Goswami Swagata , Nunes Jessica , Chiang Chi-ling , Elgamal Sara , Ventura Ann M. , Cheney Carolyn , Zapolnik Kevan , Williams Erich , Mani Rajeswaran , Frissora Frank , Mo Xiaokui , Waldmeier Lorenz , Beerli Roger R. , Peng Haiyong , Rader Christoph , Long Meixiao , Grawunder Ulf , Byrd John C. , Muthusamy Natarajan 
Published: August 2021

Abstract
Antibody-drug conjugates directed against tumor-specific targets have allowed targeted delivery of highly potent chemotherapy to malignant cells while sparing normal cells. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein with limited expression on normal adult tissues and is overexpressed on the surface of malignant cells in mantle cell lymphoma, acute lymphocytic leukemia with t(1;19)(q23;p13) translocation, and chronic lymphocytic leukemia. This differential expression makes ROR1 an attractive target for antibody-drug conjugate therapy, especially in malignancies such as mantle cell lymphoma and acute lymphocytic leukemia, in which systemic chemotherapy remains the gold standard. Several preclinical and phase 1 clinical studies have established the safety and effectiveness of anti-ROR1 monoclonal antibody–based therapies. Herein we describe a humanized, first-in-class anti-ROR1 antibody-drug conjugate, huXBR1-402-G5-PNU, which links a novel anti-ROR1 antibody (huXBR1-402) to a highly potent anthracycline derivative (PNU). We found that huXBR1-402-G5-PNU is cytotoxic to proliferating ROR1+ malignant cells in vitro and suppressed leukemia proliferation and extended survival in multiple models of mice engrafted with human ROR1+ leukemia. Lastly, we show that the B-cell lymphoma 2 (BCL2)-dependent cytotoxicity of huXBR1-402-G5-PNU can be leveraged by combined treatment strategies with the BCL2 inhibitor venetoclax. Together, our data present compelling preclinical evidence for the efficacy of huXBR1-402-G5-PNU in treating ROR1+ hematologic malignancies.
Development and characterization of prototypes for in vitro and in vivo mouse models of ibrutinib-resistant CLL
Authors: Aslan Burcu , Kismali Gorkem , Chen Lisa S. , Iles LaKesla R. , Mahendra Mikhila , Peoples Michael , Gagea Mihai , Fowlkes Natalie W. , Zheng Xiaofeng , Wang Jing , Vellano Christopher P. , Marszalek Joseph R. , Bertilaccio Maria Teresa Sabrina , Gandhi Varsha 
Published: August 2021

AbstractAlthough ibrutinib improves the overall survival of patients with chronic lymphocytic leukemia (CLL), some patients still develop resistance, most commonly through point mutations affecting cysteine residue 481 (C481) in Bruton’s tyrosine kinase (BTKC481S and BTKC481R). To enhance our understanding of the biological impact of these mutations, we established cell lines that overexpress wild-type or mutant BTK in in vitro and in vivo models that mimic ibrutinib-sensitive and -resistant CLL. MEC-1 cell lines stably overexpressing wild-type or mutant BTK were generated. All cell lines coexpressed GFP, were CD19+ and CD23+, and overexpressed BTK. Overexpression of wild-type or mutant BTK resulted in increased signaling, as evidenced by the induction of p-BTK, p-PLCγ2, and p-extracellular signal–related kinase (ERK) levels, the latter further augmented upon IgM stimulation. In all cell lines, cell cycle profiles and levels of BTK expression were similar, but the RNA sequencing and reverse-phase protein array results revealed that the molecular transcript and protein profiles were distinct. To mimic aggressive CLL, we created xenograft mouse models by transplanting the generated cell lines into Rag2−/−γc−/− mice. Spleens, livers, bone marrow, and peripheral blood were collected. All mice developed CLL-like disease with systemic involvement (engraftment efficiency, 100%). We observed splenomegaly, accumulation of leukemic cells in the spleen and liver, and macroscopically evident necrosis. CD19+ cells accumulated in the spleen, bone marrow, and peripheral blood. The overall survival duration was slightly lower in mice expressing mutant BTK. Our cell lines and murine models mimicking ibrutinib-resistant CLL will serve as powerful tools to test reversible BTK inhibitors and novel, non–BTK-targeted therapeutics.
Final results of a phase 2 clinical trial of LCL161, an oral SMAC mimetic for patients with myelofibrosis
Authors: Pemmaraju Naveen , Carter Bing Z. , Bose Prithviraj , Jain Nitin , Kadia Tapan M. , Garcia-Manero Guillermo , Bueso-Ramos Carlos E. , DiNardo Courtney D. , Bledsoe Sharon , Daver Naval G. , Popat Uday , Konopleva Marina Y. , Zhou Lingsha , Pierce Sherry , Estrov Zeev E. , Borthakur Gautam M. , Ohanian Maro , Qiao Wei , Masarova Lucia , Wang Xuemei , Mak Po Yee , Cortes Jorge , Jabbour Elias , Verstovsek Srdan 
Published: August 2021

Abstract
Outcomes in patients with high-risk and treatment-resistant myelofibrosis (MF) post-JAK inhibitor therapy remain poor, with no approved drug therapies beyond the JAK inhibitor class. In certain clinical situations, such as severe thrombocytopenia, administration of most JAK inhibitors are contraindicated. Thus, there is an unmet medical need for the development of novel agents for patients with MF. SMAC mimetics [or inhibitor of apoptosis (IAP) antagonists] induce apoptosis in cancer cells. Because these agents are hypothesized to have increased activity in a tumor necrosis factor-α cytokine-rich microenvironment, as is the case with MF, we conducted a single-center, investigator-initiated phase 2 clinical trial, with a monovalent SMAC mimetic LCL161 (oral, starting dose, 1500 mg per week) in patients with intermediate to high-risk MF. In an older group, 66% with ≥2 prior therapies and a median baseline platelet count of 52 × 103/μL and 28% with ASXL1 mutations, we observed a 30% objective response by Revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2013 criteria. Notably, 6 responding patients achieved clinical improvement of anemia: 4, hemoglobin response; 2, transfusion independence. Median OS was 34 months (range, 2.2-60.1+). Reductions of cIAPs were observed in all responders. The most common toxicity was nausea/vomiting (N/V) in 64% (mostly grade 1/2); fatigue in 46%; and dizziness/vertigo in 30%. There were 4 grade 3/4 adverse events (2, syncope; 1, N/V; 1, skin eruption/pruritis). There were 2 deaths during the study period, both unrelated to the study drug. SMAC mimetics may represent an option for older patients with thrombocytopenia or for those in whom prior JAK inhibitors has failed. This trial was registered at www.clinicaltrials.gov as #NCT02098161.
Brain multimodal co-alterations related to delay discounting: a multimodal MRI fusion analysis in persons with and without cocaine use disorder
Authors: Meade Christina S. , Li Xiang , Towe Sheri L. , Bell Ryan P. , Calhoun Vince D. , Sui Jing 
Published: August 2021

AbstractBackgroundDelay discounting has been proposed as a behavioral marker of substance use disorders. Innovative analytic approaches that integrate information from multiple neuroimaging modalities can provide new insights into the complex effects of drug use on the brain. This study implemented a supervised multimodal fusion approach to reveal neural networks associated with delay discounting that distinguish persons with and without cocaine use disorder (CUD).MethodsAdults with (n = 35) and without (n = 37) CUD completed a magnetic resonance imaging (MRI) scan to acquire high-resolution anatomical, resting-state functional, and diffusion-weighted images. Pre-computed features from each data modality included whole-brain voxel-wise maps for gray matter volume, fractional anisotropy, and regional homogeneity, respectively. With delay discounting as the reference, multimodal canonical component analysis plus joint independent component analysis was used to identify co-alterations in brain structure and function.ResultsThe sample was 58% male and 78% African–American. As expected, participants with CUD had higher delay discounting compared to those without CUD. One joint component was identified that correlated with delay discounting across all modalities, involving regions in the thalamus, dorsal striatum, frontopolar cortex, occipital lobe, and corpus callosum. The components were negatively correlated with delay discounting, such that weaker loadings were associated with higher discounting. The component loadings were lower in persons with CUD, meaning the component was expressed less strongly.ConclusionsOur findings reveal structural and functional co-alterations linked to delay discounting, particularly in brain regions involved in reward salience, executive control, and visual attention and connecting white matter tracts. Importantly, these multimodal networks were weaker in persons with CUD, indicating less cognitive control that may contribute to impulsive behaviors.
Comparative analysis of carbapenemases, RND family efflux pumps and biofilm formation potential among Acinetobacter baumannii strains with different carbapenem susceptibility
Authors: Zhang Yanpeng , Fan Bing , Luo Yong , Tao Zhiyuan , Nie Yongbo , Wang Yongtao , Ding Fanglin , Li Yanwu , Gu Dayong 
Published: August 2021

Abstract
Aim
This study has conducted a comparative analysis of common carbapenemases harboring, the expression of resistance-nodulation-cell division (RND) family efflux pumps, and biofilm formation potential associated with carbapenem resistance among Acinetobacter baumannii (A. baumannii) strains with different carbapenem susceptibility. Methods: A total of 90 isolates of A. baumannii from two tertiary hospitals of China were identified and grouped as carbapenem susceptible A. baumannii (CSAB) strains and carbapenem non-susceptible A. baumannii (CnSAB) strains based on the susceptibility to imipenem. Harboring of carbapenemase genes, relative expression of RND family efflux pumps and biofilm formation potential were compared between the two groups. Result: Among these strains, 12 (13.3 %) strains were divided into the CSAB group, and 78 (86.7 %) strains into the CnSAB group. Compared with CSAB strains, CnSAB strains increased distribution of blaOXA−23 (p < 0.001) and ISAba1/blaOXA−51−like (p = 0.034) carbapenemase genes, and a 6.1-fold relative expression of adeB (p = 0.002), while CSAB strains led to biofilm formation by 1.3-fold than CnSAB strains (p = 0.021).

Conclusions
Clinically, harboring more blaOXA−23−like and ISAba1/blaOXA−51−like complex genes and overproduction of adeABC are relevant with carbapenem resistance, while carbapenem susceptible strains might survive the stress of antibiotic through their ability of higher biofilm formation.