bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colocalization of Carbonic Anhydrase 9 Expression and Cell Proliferation in Human Head and Neck Squamous Cell Carcinoma
Authors: Hoogsteen Ilse J. , Marres Henri A.M. , Wijffels Karien I.E.M. , Rijken Paul F.J.W. , Peters Johannes P.W. , van den Hoogen Franciscus J.A. , Oosterwijk Egbert , van der Kogel Albert J. , Kaanders Johannes H.A.M. 
Published: June 2022

Abstract
Purpose: Tumor cells undergo a variety of biological changes under sustained hypoxic conditions, allowing cells to survive and retain their clonogenic potential. The purpose of this study is to relate the expression of the hypoxia marker carbonic anhydrase 9 (CA9) to the uptake of iododeoxyuridine (IdUrd), a marker of proliferation, in head and neck squamous cell carcinomas. Colocalization of IdUrd and CA9 may identify an important subpopulation of tumor cells that might be responsible for repopulation and disease progression.
Experimental Design: Expression of CA9, IdUrd labeling, and colocalization between IdUrd and CA9 was examined by immunohistochemistry in biopsies of head and neck squamous cell carcinomas. Biopsies were taken from 51 patients recruited between 1998 and 2001 after administration of the proliferation marker IdUrd.
Results: A large variation was observed between the tumors in CA9 expression (range 0-39%), IdUrd labeling (range 0-81%), and colocalization between IdUrd and CA9 [FId(CA9); range 0-53%]. FId(CA9), the fraction of IdUrd-labeled cells positive for CA9, was highest at an intermediate distance from the blood vessels (100-150 μm). IdUrd labeling was higher in T4 carcinomas relative to lower stage tumors (P = 0.04). High FId(CA9) correlated with the worst disease-free survival rates (P = 0.04).
Conclusions: Colocalization between IdUrd labeling and CA9 expression was observed in head and neck squamous cell carcinomas, suggesting the presence of a population of tumor cells under intermediate hypoxic conditions which still has proliferative capacity. The size of this subpopulation may be indicative of tumor aggressiveness and is associated with the worst disease-free survival rates.
50 Years of Preclinical Anticancer Drug Screening: Empirical to Target-Driven Approaches
Authors: Suggitt Marie , Bibby Michael C. 
Published: June 2022

Abstract
The number of anticancer agents that fail in the clinic far outweighs those considered effective, suggesting that the selection procedure for progression of molecules into the clinic requires improvement. The value of any preclinical model will ultimately depend on its ability to accurately predict clinical response. This review focuses on the major contributions of preclinical screening models to anticancer drug development over the past 50 years. Over time, a general transition has been observed from the empirical drug screening of cytotoxic agents against uncharacterized tumor models to the target-orientated drug screening of agents with defined mechanisms of action. New approaches to anticancer drug development involve the molecular characterization of models along with an appreciation of the pharmacodynamic and pharmacokinetic properties of compounds [e.g., the US National Cancer Institute (NCI) in vitro 60-cell line panel, hollow fiber assay, and s.c. xenograft]. Contributions of other potentially more clinically relevant in vivo tumor models including orthotopic, metastatic, and genetically engineered mouse models are also reviewed. Although this review concentrates on the preclinical screening efforts of the NCI, European efforts are not overlooked. Europe has played a key role in the development of new anticancer agents. The two largest academic drug development groups, the European Organisation for Research and Treatment of Cancer and Cancer Research UK, have been collaborating with the NCI in the acquisition and screening of compounds since the 1970s. As with the drug development process internationally, rational pharmacodynamic approaches have more recently been adopted by these two groups.
Glycogen Synthase Kinase-3 Inhibition Sensitizes Pancreatic Cancer Cells to Chemotherapy by Abrogating the TopBP1/ATR-Mediated DNA Damage Response
Authors: Ding Li , Madamsetty Vijay S. , Kiers Spencer , Alekhina Olga , Ugolkov Andrey , Dube John , Zhang Yu , Zhang Jin-San , Wang Enfeng , Dutta Shamit K. , Schmitt Daniel M. , Giles Francis J. , Kozikowski Alan P. , Mazar Andrew P. , Mukhopadhyay Debabrata , Billadeau Daniel D. 
Published: June 2022

Abstract

Purpose:
Pancreatic ductal adenocarcinoma (PDAC) is a predominantly fatal common malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies including PDAC.

Experimental Design:
Pancreatic cancer cell lines and patient-derived xenografts were treated with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. Activation of the DNA damage response pathway and S-phase arrest induced by gemcitabine were assessed in pancreatic tumor cells with pharmacologic inhibition or siRNA depletion of GSK-3 kinases by immunoblotting, flow cytometry, and immunofluorescence.

Results:
9-ING-41 treatment significantly increased pancreatic tumor cell killing when combined with chemotherapy. Inhibition of GSK-3 by 9-ING-41 prevented gemcitabine-induced S-phase arrest suggesting an impact on the ATR-mediated DNA damage response. Both 9-ING-41 and siRNA depletion of GSK-3 kinases impaired the activation of ATR leading to the phosphorylation and activation of Chk1. Mechanistically, depletion or knockdown of GSK-3 kinases resulted in the degradation of the ATR-interacting protein TopBP1, thus limiting the activation of ATR in response to single-strand DNA damage.

Conclusions:
These data identify a previously unknown role for GSK-3 kinases in the regulation of the TopBP1/ATR/Chk1 DNA damage response pathway. The data also support the inclusion of patients with PDAC in clinical studies of 9-ING-41 alone and in combination with gemcitabine.
Poor Cortical Venous Opacification on Baseline Computed Tomography Angiography Predicts Parenchymal Hemorrhage After Thrombectomy
Authors: Bala Fouzi , Singh Nishita , Menon Bijoy K. , Demchuk Andrew M. , Poppe Alexandre Y. , McTaggart Ryan A. , Nogueira Raul G. , Buck Brian H. , Goyal Mayank , Hill Michael D. , Almekhlafi Mohammed A. ,   the ESCAPE‐NA1 investigators
Published: June 2022

Background
Although the association between cortical venous opacification (VO) and clinical outcomes has been shown in previous studies, little is known about the relationship between parenchymal hemorrhage (PH) and VO in patients with acute stroke. We aimed to determine whether cortical VO assessed on computed tomography angiography correlates with the risk of PH following endovascular treatment.

Methods
This is a post hoc analysis of the ESCAPE NA‐1 (Efficacy and Safety of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial. Control‐arm patients with adequate venous assessment on computed tomography angiography were included. Any PH and symptomatic intracranial hemorrhage were compared between patients with poor VO (cortical vein opacification score<3) versus good opacification (cortical vein opacification score≥3). The relationships with unfavorable functional outcome (90‐day modified Rankin scale 3–6) and 24‐hour infarct volume were assessed. Multivariable logistic and linear regressions were performed.

Results

Among the 545 patients that met the inclusion criteria, 55 (10.2%) had PH and 21 (3.9%) had symptomatic intracranial hemorrhage. Poor VO was observed in 286 (52.5%) patients (median age, 71 years; 51.4% women). PH was more frequent in the patients with poor VO compared with good VO: 43 of 283 (15.2%) versus 12 of 257 (4.7%) (adjusted odds ratio, 3.43; [95% CI, 1.66–7.10]). Symptomatic intracranial hemorrhage was not significantly higher in the poor versus good opacification groups: 14 of 283 (5.0%) versus 7 of 257 (2.7%). Poor opacification was a predictor of unfavorable functional outcome (adjusted odds ratio, 3.01; [95% CI, 1.95–4.64];
P
<0.001), and larger final infarct volume (adjusted B 0.74; [95% CI, 0.45–1.03];
P
<0.001).

Conclusions
Poor VO on computed tomography angiography is strongly associated with an increased risk of PH and worse clinical outcomes after endovascular treatment, and therefore it may be used as a tool for risk stratification in patients with stroke.
Correlation Between Intolerance of Uncertainty and Post-Operative Regret in Otolaryngology Patients
Authors: Cleveland Chelsea N. , Virgen Celina , Steinman Shari A. , Callaham Sarah , Wanstreet Tyler , Carr Michele M. 
Published: June 2022

Objective: To determine if intolerance of uncertainty, depression, anxiety, worry, or stress are related to post-op regret in otolaryngology patients. Methods: Adult patients or parents giving consent for pediatric patients meeting criteria for otolaryngologic surgery were recruited and completed the Intolerance of Uncertainty Scale (IUS-12), Penn State Worry Questionnaire (PSWQ), and Depression, Anxiety and Stress Scale-21 (DASS-21) preop and the Decisional Regret (DR) scale 1-month post-op. Pearson correlations were calculated. Results: The cohort included 109 patients, 73 (67%) males and 36 (33.3%) females. 43 (39.5%) were college graduates and 66 (60.9%) were not. Mean IUS-12 score was 22.9 (95% CI 21.0-24.8), mean PSWQ score was 46.9 (95% CI 44.5-49.3). DASS-21 mean score was 11.9 (95% CI 9.6-14.3). Mean DR score was 11.1 (95% CI 8.6-13.6). IUS-12 subscales Prospective Anxiety mean score was 14.2 (95% CI 12.8-15.5) and Inhibitory Anxiety mean score was 16.5 (95% CI 14.5-18.6). The Pearson correlation coefficient for post-op DR and total preop IUS was .188 ( P = .027) and the correlation coefficient for post-op DR and preop Prospective Anxiety subscale of IUS score was .174 ( P = .037). Correlations with PSWQ and DASS-21 scores and DR were not statistically significant. Conclusion: Intolerance of uncertainty is a psychological construct that is associated with post-op DR. More work is needed to determine whether screening for IU and behavior modification directed at IU for those with high levels would improve post-op decisional regret.
Synthesis, characterization, and properties of a new polyurethane elastomer based on tragacanth gum polysaccharide
Authors: Badakhshanian Elham , Ghaemy Mousa 
Published: June 2022

This study prepared a type of bio-based elastomeric polyurethane from tragacanth gum (TG). TG is a natural polysaccharide with many hydroxyl groups that can be used as a chain extender and a crosslinker to react with the isocyanate groups in polyurethane prepolymer to form a highly branched and crosslinked polyurethane with high molecular weight and good mechanical properties. The chemical structure of the prepolymer and the thermal and mechanical properties of the prepared polyurethane were studied by Fourier transform infrared, nuclear magnetic resonance, scanning electron microscopy, thermal gravimetric analysis, dynamic mechanical thermal analysis, and tensile strength tester. The properties of the polyurethane-based on TG (TG-PU) were compared with the properties of the PU based on only polyethylene glycol. The TG-PU sample with 0.5 g TG showed a tensile strength of 288% and the glass transition temperature (Tg) of 33% higher than the tensile strength and Tg of PU without TG. We expect these findings to widen the range of preparation and applications of bio-based polyurethane materials.
Testing the Effects of a Utility Value Intervention in an Online Research Methods Course: A Conceptual Replication of Hulleman et al. (2017, Study 2)
Authors: Price Paul C. , Crisosto Kiana , Carvalho Anthony , Jones Constance J. , McCready Meaghan , Shaver Amber , Wiemann Andrea N. 
Published: June 2022

Background Utility-value (UV) classroom interventions typically involve students completing assignments that involve writing about the usefulness of the course material. They are widely recommended and have received some empirical support. Objective This study tested the effectiveness of a UV intervention in an online research methods course. It was a conceptual replication of a study by Hulleman et al. (2017, Study 2). Method Students ( N = 264) were randomly assigned to complete three assignments that required them to write about the usefulness of course material or three assignments that required them to summarize course material. The groups were compared in terms of their scores on a research methods knowledge test, their final papers, their final exams, and their final point totals, along with measures of the interestingness and usefulness of the course material. Results There were no differences between conditions on any of the outcome variables. Conclusion The UV intervention was ineffective. Further research is needed to establish the conditions under which such interventions are and are not effective. Teaching Implications UV interventions do not necessarily improve student performance. Instructors who use them should consider doing so in a way that allows for an assessment of their effect in their local context.
‘Never think doing a job is easy’: The lived experience of work for people who have an intellectual and developmental disability
Authors: Ramsey Diana , Cameron Josh , Harrison Rebecca , Young Sharon 
Published: June 2022

Introduction The proportion of people with an intellectual or developmental disability (IDD) in paid employment is low internationally despite policy efforts. Evidence suggests multiple and varied explanations for this, including organisational, social and personal barriers. That evidence has not focused on first-person experiences which may provide a depth of understanding and explanation of the work-related experiences of people with IDD. Method A hermeneutic phenomenological approach and an exploratory research method of a ‘creative collaborative partnership’ was adopted to illuminate the work-related experiences of six people with a mild IDD. Findings Six work stories composed of narratives and visual images were collaboratively created revealing a complex range of positive and negative experiences and perspectives of paid work. Five collective narrative frames emerged: the quest ‘to do’, navigating bureaucratic seas, finding a good fit, forging of identity and finding both friend and foe. Conclusion The collaborators’ stories highlighted that individuals supporting people with IDD towards or in work, including occupational therapists, need to adopt a nuanced systemic perspective of the context surrounding the person. This includes identifying allies and allowing people with IDD to decide how (if at all) they describe their IDD status to others as they establish their worker identity.
Artificial Intelligence and Machine Learning in Cancer Research: A Systematic and Thematic Analysis of the Top 100 Cited Articles Indexed in Scopus Database
Authors: Musa Ibrahim H. , Afolabi Lukman O. , Zamit Ibrahim , Musa Taha H. , Musa Hassan H. , Tassang Andrew , Akintunde Tosin Y. , Li Wei 
Published: June 2022

Introduction Cancer is a major public health problem and a global leading cause of death where the screening, diagnosis, prediction, survival estimation, and treatment of cancer and control measures are still a major challenge. The rise of Artificial Intelligence (AI) and Machine Learning (ML) techniques and their applications in various fields have brought immense value in providing insights into advancement in support of cancer control. Methods A systematic and thematic analysis was performed on the Scopus database to identify the top 100 cited articles in cancer research. Data were analyzed using RStudio and VOSviewer.Var1.6.6. Results The top 100 articles in AI and ML in cancer received a 33 920 citation score with a range of 108 to 5758 times. Doi Kunio from the USA was the most cited author with total number of citations (TNC = 663). Out of 43 contributed countries, 30% of the top 100 cited articles originated from the USA, and 10% originated from China. Among the 57 peer-reviewed journals, the “Expert Systems with Application” published 8% of the total articles. The results were presented in highlight technological advancement through AI and ML via the widespread use of Artificial Neural Network (ANNs), Deep Learning or machine learning techniques, Mammography-based Model, Convolutional Neural Networks (SC-CNN), and text mining techniques in the prediction, diagnosis, and prevention of various types of cancers towards cancer control. Conclusions This bibliometric study provides detailed overview of the most cited empirical evidence in AI and ML adoption in cancer research that could efficiently help in designing future research. The innovations guarantee greater speed by using AI and ML in the detection and control of cancer to improve patient experience.
Knowledge and practice towards early orthodontic problems among general dentists and paediatric dentists
Authors: Abdelmagid Sara M E , Abass Shaza K 
Published: June 2022

Objectives: To assess the knowledge, practice and challenges faced by general dental practitioners (GDPs), paediatric dentists (PDs) and postgraduate paediatric dentistry students (PGPDSs) in diagnosing and managing early orthodontic problems. Design: Cross-sectional study. Methods: A total of 159 dentists were enrolled in this study (121 GDPs, 21 PDs and 17 PGPDSs). Data were collected using a self-administered questionnaire involving two sections. Section A included questions regarding demographic features and orthodontic practice. Section B included photos of 12 orthodontic cases that needed early intervention. Knowledge and practice were assessed using six questions for each case that was then rated using predefined scores of poor (score <50%), average (score 50%–75%) and good (score >75%). Results: The knowledge scores regarding the identification of early orthodontic problems were average among the three groups with GDPs having the lowest score ( P = 0.0001). The knowledge scores regarding the selection of optimal treatment time were average among the PDs and PGPDSs, and poor among GDPs. GDPs tended to refer most of their cases to an orthodontist except for cases of thumb sucking. PDs and PGPDSs were more confident in treating anterior crossbite, thumb sucking habits and delayed eruption of incisors. All participants scored ‘poor’ regarding the selection of an appropriate orthodontic appliance. There was no significant correlation between knowledge and practice ( P > 0.05). Conclusion: PDs and PGPDSs showed higher knowledge and practice scores when compared to GDPs. For all three groups included in this study, lack of clinical skills was the main reason for not treating early orthodontic problems.
Angiosarcoma and Vascular Surgery: A Case Report and Review of Literature
Authors: May Lee Marco , Pierobon Elena , Riva Giulio , Germi Lerica , Feliciani Claudio , Naldi Luigi 
Published: June 2022

Introduction: Angiosarcomas (AS) are rare and aggressive neoplasms originating from the endothelium: they represent less than 2% of all soft tissue sarcomas and usually have a poor prognosis. Although more often primary, different risk factors have been described and some cases are associated with vascular surgery. Materials and Methods: We present the case of an 84-year-old man who developed an AS on his thigh 3 years after a popliteal bypass with autologous saphenous vein. We performed a thorough review of the literature describing the main characteristics of the 25 cases (including ours) of AS associated with vascular surgery reported from 1981 to 2022. Results: Most of the patients were males (21 men vs 4 women) with a range age of 50-84 years. Most of AS are associated with Dacron grafts (12 cases), the overall mean time to onset is 7.8 years after surgery. The most common presenting symptoms are pain (20 cases) and weight loss (10 cases), while cutaneous presentation is uncommon; indeed, violaceous and painful papules, plaques, nodules, and skin ulceration have been found in 3 cases only. Due to unspecific symptoms, differential diagnosis is often difficult and a biopsy for histological confirmation is mandatory. Conclusion: Even if it seems to be a very rare complication, AS should always be considered in patients with compatible symptoms and who have undergone vascular surgery in the past.
Tactile Sensation Improves Following Motor Rehabilitation for Chronic Stroke: The VIGoROUS Randomized Controlled Trial
Authors: Borstad Alexandra , Nichols-Larsen Deborah , Uswatte Gitendra , Strahl Nancy , Simeo Marie , Proffitt Rachel , Gauthier Lynne 
Published: June 2022

Background. Up to 85% of people with chronic stroke experience somatosensory impairment, which contributes to poor sensorimotor control and non-use of the affected limb. Neurophysiological mechanisms suggest motor rehabilitation may improve tactile sense post-stroke, however, somatosensory recovery has rarely been reported in controlled trials. Objective. To compare the effect of four upper limb motor rehabilitation programs on the recovery of tactile sensation in adults with chronic stroke. Methods. Adults with chronic stroke and mild or moderate upper extremity hemiparesis ( n = 167) were enrolled in a multi-site randomized controlled trial. Participants completed three weeks of gaming therapy, gaming therapy with additional telerehabilition, Constraint-Induced Movement therapy, or traditional rehabilitation. Here, we report the results of a secondary outcome, tactile sensation, measured with monofilaments, before and after treatment, and 6 months later. Results. A mixed-effects general linear model revealed similar positive change in tactile sensitivity regardless of the type of training. On average, participants were able to detect a stimulus that was 32% and 33% less after training and at 6-month follow-up, respectively. One-third of participants experienced recategorization of their level of somatosensory impairment (e.g., regained protective sensation) following training. Poorer tactile sensation at baseline was associated with greater change. Conclusions. About one-third of individuals with mild/moderate chronic hemiparesis experience sustained improvements in tactile sensation following motor rehabilitation, regardless of the extent of tactile input in the rehabilitation program. Potential for sensory improvement is an additional motivator for those post-stroke. Characteristics of those who improve and mechanisms of improvement are important future questions. Clinicaltrials.gov NCT02631850
Does Time to Operative Intervention of Distal Radius Fractures Influence Outcomes?
Authors: Ahmad Farhan , Neral Mithun , Hoyen Harry , Simcock Xavier , Malone Kevin 
Published: June 2022

Background: No investigation has analyzed the time from injury to operative intervention and its effect on complications and functional outcomes in distal radius fractures. This investigation aimed to establish whether the time to surgical intervention from injury was associated with the observed rate of complications in distal radius fractures. Methods: A retrospective review of all orthopedic trauma patients who came to our center was conducted from 2008 through 2014. Patients who sustained closed distal radius fractures were included. A postoperative complication following distal radius fracture was defined as reoperation, superficial or deep infection, complex regional pain syndrome, new-onset carpal tunnel syndrome, tendon irritation, and symptomatic hardware. Results: In all, 190 patients were included in the study with a mean age of 48 years (SD ±14.7). According to the AO-Müller/Orthopaedic Trauma Association classification, radiographs revealed 80 A fractures, 15 B fractures, and 95 C fractures. Thirty distal radii were fixed within 0 to 3 days after injury, 91 patients within 4 to 10 days, and 69 patients after 10 days. Overall, 28 complications (14.7%) were identified. There was no statistical difference in the rate of complications between the time interval groups ( P = .17). Conclusions: Despite the increased popularity of surgical intervention for distal radius fractures, the optimal parameters to maximize patient outcomes have yet to be clearly defined. Time to intervention did not affect the rate of postoperative complication and range of motion.