bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Donor-Recipient Age and Sex Compatibility in the Outcomes of Deep Anterior Lamellar Keratoplasties
Authors: Ong Hon Shing , Chiam Nathalie , Htoon Hla Myint , Kumar Ashish , Arundhati Anshu , Mehta Jodhbir S. 
Published: January 2022

PurposeCorneal transplantations are the commonest allogenic transplant surgeries performed worldwide. Transplantable grade donor cornea is a finite resource. There is thus an impetus for eye banks to optimize the use of each harvested cornea, and clinicians to minimize the risks of graft rejection and failure. With better survival and lower rejection rates, anterior lamellar keratoplasty has gained popularity as an alternative technique to full-thickness penetrating keratoplasty, for the treatment of corneal stromal diseases. This study evaluated the effects of donor-recipient age- and sex-matching on the outcomes of eyes that had undergone deep anterior lamellar keratoplasty (DALK) surgeries.DesignObservational cross-sectional study (national corneal graft registry data).SubjectsAll DALK surgeries performed in a tertiary ophthalmic hospital over an 11-year period.MethodsTo analyse the effects of donor-recipient sex-matching, transplantations were classified as “presumed H-Y incompatible” (male donor to female recipient) or “presumed H-Y compatible” (all other donor-recipient sex combinations). For age-matching, differences in donor and recipient ages were calculated. Cox proportional hazards regressions were used to evaluate the influence of donor-recipient sex-matching and age-matching on graft failure and rejection.Main Outcome MeasuresRates of graft failure and rejection within each group.Results401 eyes were included. 271 (67.6%) transplants were presumed H-Y compatible. 29 (7.2%) grafts failed and 9 (2.2%) grafts rejected. There were trends of lower hazard ratios (HRs) in graft failure and rejection in the presumed H-Y compatible group [HRs: 0.59 (95% CI 0.20–1.77,p= 0.34) and 0.93 (95% CI 0.22–3.89,p= 0.926), respectively]. Median difference in age between recipients and donors was 15.0 years (IQR −2.8–34.3). The HRs of graft failure and rejection were not influenced by donor-recipient age [HRs per 1-year increase in age difference: 0.995 (95% CI 0.98–1.01,p= 0.483) and 1.01 (95% CI 0.99–1.03,p= 0.394), respectively].ConclusionIn eyes that had undergone DALK surgeries, no significant influence of donor-recipient sex- or age-matching on graft rejection and failure was observed. Without strong evidence and the limitations of obtaining sample sizes required for an adequately powered study, the benefits of sex- and age-matching of donors and recipients during graft allocation for DALK surgeries is currently inconclusive.
A Patients' Perspective Towards the Injection Devices for Humira® and Imraldi® in a Nationwide Switching Program
Authors: Karlsdottir Kristin , Gunnarsdottir Anna I. , Grondal Gerdur , Love Thorvardur J. , Stefansdottir Elinborg , Davidsdottir Loa G. , Thorleifsdottir Ragna H. , Gudbjornsson Bjorn 
Published: January 2022

ObjectiveDue to a tender process in Iceland, all patients on Humira® were switched nationwide to its biosimilar Imraldi® in March 2019. The study aimed to explore the patient's perspective of the Humira® and Imraldi® injection devices.MethodsA standard telephone interview was carried out among patients with inflammatory arthritis, inflammatory bowel disease and psoriasis, who underwent this nationwide switching program a few months earlier.ResultsThe response rate was 84.5% (n = 198). The average age was 50.8 years, and 53.5% were female. The patients self-administered the drugs in 96% of the cases. The majority (90.5%) stated that they received individualized instruction on using the Humira® pen, compared to 18.2% who accepted instruction in the case of the Imraldi® pen. Almost half (46.6%) of the patients found it more difficult to use the Imraldi® pen than the Humira® pen, while only 12.5% found the Imraldi® pen easier to use. Firstly, these differences were due to more painful insertion of the needle (62.2%) and secondly, due to the experience, the injection process was different (63.0%).ConclusionPatients with inflammatory disorders who have been treated regularly with adalimumab preferred the Humira® injection device over the Imraldi® device, according to our results. After all, these injection devices' structure and content are not the same, although both contain the same active ingredient, i.e. adalimumab. Our results highlight the importance of thorough information, not only with an information letter but also with the possibilities for individualized introduction in planning switching to biosimilars.
Urinary Tract Infection Etiological Profiles and Antibiotic Resistance Patterns Varied Among Different Age Categories: A Retrospective Study From a Tertiary General Hospital During a 12-Year Period
Authors: Huang Lei , Huang Chenwei , Yan Yan , Sun Liying , Li Haixia 
Published: January 2022

BackgroundUrinary tract infections (UTIs) are among the most common infections worldwide. With continuing trends of antibiotic resistance, the etiological distribution and antibiotic susceptibility surveillance are of great importance for empirical antimicrobial therapy. The risk factors and clinical circumstances of UTI among different age categories varied; thus, the pathogens and antimicrobial susceptibilities of UTI may also change with age. The aim of this study was to compare the etiological profiles and antibiotic resistance patterns of UTIs sorted by different age categories from a tertiary general hospital during a 12-year period.MethodsAll positive urine culture results from non-repetitive UTI patients in our hospital from January 2009 to December 2020 were collected retrospectively. The microbial distribution and antibiotic resistance rates were analyzed by WHONET 5.6 software. The etiological profiles sorted by different age categories (newborn, pediatric, adult, and geriatric) and antibiotic resistance rates of the top five pathogens were analyzed.ResultsA total of 13,308 non-repetitive UTI patients were included in our study. Enterococcus faecium was dominant in newborn (45%, n = 105), and replaced by Escherichia coli in pediatric (34%, n = 362), adult (43%, n = 3,416), and geriatric (40%, n = 1,617), respectively. The etiological profiles of different age categories were divergent, sorted by genders (male and female) and ward types (outpatient, inpatient, ICU, and emergency). E. coli, Klebsiella pneumoniae, Enterococcus faecalis, E. faecium, and Pseudomonas aeruginosa were the top five pathogens in all age categories. The resistance rates of cefoperazone–sulbactam and piperacillin–tazobactam in E. coli were low in all age categories. The resistance rates of other cephalosporins, carbapenems, and fluoroqinolones in K. pneumoniae were higher in geriatric patients overall. E. faecium was more resistant than E. faecalis in all age categories. Multidrug resistance increased with age, which was more serious in geriatric patients.ConclusionThe UTI etiological profiles and antibiotic resistance patterns varied among different age categories, especially in pediatric and geriatric patients; thus, a different antibiotic therapy for various age categories should be considered when initiating empirical antimicrobial therapies.
Molecular Architecture of the Antiophidic Protein DM64 and its Binding Specificity to Myotoxin II From Bothrops asper Venom
Authors: Soares Barbara S. , Rocha Surza Lucia G. , Bastos Viviane A. , Lima Diogo B. , Carvalho Paulo C. , Gozzo Fabio C. , Demeler Borries , Williams Tayler L. , Arnold Janelle , Henrickson Amy , Jørgensen Thomas J. D. , Souza Tatiana A. C. B. , Perales Jonas , Valente Richard H. , Lomonte Bruno , Gomes-Neto Francisco , Neves-Ferreira Ana Gisele C. 
Published: January 2022

DM64 is a toxin-neutralizing serum glycoprotein isolated from Didelphis aurita, an ophiophagous marsupial naturally resistant to snake envenomation. This 64 kDa antitoxin targets myotoxic phospholipases A2, which account for most local tissue damage of viperid snakebites. We investigated the noncovalent complex formed between native DM64 and myotoxin II, a myotoxic phospholipase-like protein from Bothrops asper venom. Analytical ultracentrifugation (AUC) and size exclusion chromatography indicated that DM64 is monomeric in solution and binds equimolar amounts of the toxin. Attempts to crystallize native DM64 for X-ray diffraction were unsuccessful. Obtaining recombinant protein to pursue structural studies was also challenging. Classical molecular modeling techniques were impaired by the lack of templates with more than 25% sequence identity with DM64. An integrative structural biology approach was then applied to generate a three-dimensional model of the inhibitor bound to myotoxin II. I-TASSER individually modeled the five immunoglobulin-like domains of DM64. Distance constraints generated by cross-linking mass spectrometry of the complex guided the docking of DM64 domains to the crystal structure of myotoxin II, using Rosetta. AUC, small-angle X-ray scattering (SAXS), molecular modeling, and molecular dynamics simulations indicated that the DM64-myotoxin II complex is structured, shows flexibility, and has an anisotropic shape. Inter-protein cross-links and limited hydrolysis analyses shed light on the inhibitor’s regions involved with toxin interaction, revealing the critical participation of the first, third, and fifth domains of DM64. Our data showed that the fifth domain of DM64 binds to myotoxin II amino-terminal and beta-wing regions. The third domain of the inhibitor acts in a complementary way to the fifth domain. Their binding to these toxin regions presumably precludes dimerization, thus interfering with toxicity, which is related to the quaternary structure of the toxin. The first domain of DM64 interacts with the functional site of the toxin putatively associated with membrane anchorage. We propose that both mechanisms concur to inhibit myotoxin II toxicity by DM64 binding. The present topological characterization of this toxin-antitoxin complex constitutes an essential step toward the rational design of novel peptide-based antivenom therapies targeting snake venom myotoxins.
Evaluating the Association of Calcified Neurocysticercosis and Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis in a Large Cohort of Patients With Epilepsy
Authors: Secchi Thaís Leite , Brondani Rosane , Bragatti José Augusto , Bizzi Jorge Wladimir Junqueira , Bianchin Marino Muxfeldt 
Published: January 2022

BackgroundNeurocysticercosis (NCC) is a parasitic infection of the central nervous system that has been associated with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). However, this association has not been completely established.ObjectiveTo evaluate the prevalence of calcified NCC (cNCC), its characteristics and a possible association between cNCC and MTLE-HS in a cohort of 731 patients with epilepsy.MethodsWe review clinical, EEG and neuroimaging findings of 731 patients with epilepsy. From these, 659 had CT-scans and 441 patients had complete neuroimaging with CT-scans and MRI. In these patients, we review the prevalence and characteristic of epilepsy in cNCC and in MTLE-HS patients.ResultsForty-two (6.4%) of the 659 patients studied with CT-scans had cNCC. cNCC lesions were more frequent in women than in men (n= 33–78.6% vs.n= 09–21.4%, respectively; OR = 3.64;(95%CI = 1.71–7.69);p&lt; 0.001). cNCC was more often in patients who developed epilepsy later in life, in older patients, in patients who had a longer history of epilepsy, and in those with a lower educational level. MTLE–HS was observed in 93 (21.1%) of 441 patients that had complete neuroimaging, and 25 (26.9%) of these 93 patients also had cNCC. Calcified NCC was observed in only 17 (4.9%) of the remaining 348 patients that had other types of epilepsy rather than MTLE-HS. Thus, in our cohort, cNCC was more frequently associated with MTLE-HS than with other forms of epilepsy, O.R. = 11.90;(95%CI = 6.10–23.26);p&lt; 0.0001).ConclusionsAs expected, in some patients the epilepsy was directly related to cNCC lesional zone, although this was observed in a surprisingly lower number of patients. Also, cNCC lesions were observed in other forms of epilepsy, a finding that could occur only by chance, with epilepsy probably being not related to cNCC at all. In this cohort, cNCC was very commonly associated with MTLE-HS, an observation in agreement with the hypothesis that NCC can contribute to or directly cause MTLE-HS in many patients. Given the broad world prevalence of NCC and the relatively few studies in this field, our findings add more data suggesting a possible and intriguing frequent interplay between NCC and MTLE-HS, two of the most common causes of focal epilepsy worldwide.
Impact of Body Composition During Neoadjuvant Chemoradiotherapy on Complications, Survival and Tumor Response in Patients With Locally Advanced Rectal Cancer
Authors: Liu Zhenzhen , Lu Siyi , Wang Yuxia , Lin Xinyi , Ran Peng , Zhou Xin , Fu Wei , Wang Hao 
Published: January 2022

BackgroundTo explore the impact of body composition before neoadjuvant chemoradiotherapy (pre-NCRT) and after neoadjuvant chemoradiotherapy (post-NCRT) on complications, survival, and tumor response in patients with locally advanced rectal cancer (LARC).MethodsPatients with LARC who underwent radical surgery after NCRT between Ja 22nuary 2012 and March 2019 were studied. Body composition parameters, including skeletal muscle area (SMA), muscle density (MD), visceral fat area (VFA), total abdominal fat area (TAFA), and subcutaneous fat area (SFA), was identified at the third lumbar vertebra level on computed tomography (CT). The patients were divided into two groups based on the sex-specific quartile values of SMA, MD, VFA, TAFA, SFA, and body composition change. Patient characteristics, short- and long-term postoperative complications, survival, and tumor response were analyzed.ResultsA total of 122 eligible patients were enrolled. Body composition parameters, except MD, were strongly correlated with BMI (p &lt; 0.001). Pre-NCRT low MD (p = 0.04) and TAFA loss (p = 0.02) were significantly correlated with short- and long-term ileus, respectively. Pre-NCRT low SMA was a significant prognostic factor for both disease-free survival (DFS) (HR 2.611, 95% CI 1.129–6.040, p = 0.025) and cancer-specific survival (CSS) (HR 3.124, 95% CI 1.030–9.472, p = 0.044) in the Cox regression multivariate analysis. Multivariate logistic regression analysis identified post-NCRT SFA (OR 3.425, 95% CI 1.392–8.427, p = 0.007) and SFA loss (OR 3.358, 95% CI 1.214–9.289, p = 0.02) as independent risk factors for tumor regression grade (TRG) and downstaging, respectively.ConclusionPre-NCRT low MD and TAFA loss were related to a high incidence of short- and long-term ileus, respectively. Pre-NCRT low SMA was a significant prognostic factor for CSS and DFS. Post-NCRT SFA and SFA loss were independent risk factors for TRG and downstaging, respectively.
Improved Diagnostic Accuracy of Ameloblastoma and Odontogenic Keratocyst on Cone-Beam CT by Artificial Intelligence
Authors: Chai Zi-Kang , Mao Liang , Chen Hua , Sun Ting-Guan , Shen Xue-Meng , Liu Juan , Sun Zhi-Jun 
Published: January 2022

ObjectiveThe purpose of this study was to utilize a convolutional neural network (CNN) to make preoperative differential diagnoses between ameloblastoma (AME) and odontogenic keratocyst (OKC) on cone-beam CT (CBCT).MethodsThe CBCT images of 178 AMEs and 172 OKCs were retrospectively retrieved from the Hospital of Stomatology, Wuhan University. The datasets were randomly split into a training dataset of 272 cases and a testing dataset of 78 cases. Slices comprising lesions were retained and then cropped to suitable patches for training. The Inception v3 deep learning algorithm was utilized, and its diagnostic performance was compared with that of oral and maxillofacial surgeons.ResultsThe sensitivity, specificity, accuracy, and F1 score were 87.2%, 82.1%, 84.6%, and 85.0%, respectively. Furthermore, the average scores of the same indexes for 7 senior oral and maxillofacial surgeons were 60.0%, 71.4%, 65.7%, and 63.6%, respectively, and those of 30 junior oral and maxillofacial surgeons were 63.9%, 53.2%, 58.5%, and 60.7%, respectively.ConclusionThe deep learning model was able to differentiate these two lesions with better diagnostic accuracy than clinical surgeons. The results indicate that the CNN may provide assistance for clinical diagnosis, especially for inexperienced surgeons.
Targeting Thyrointegrin αvβ3 Using Fluorobenzyl Polyethylene Glycol Conjugated Tetraiodothyroacetic Acid (NP751) in Acute Myeloid Leukemia
Authors: Darwish Noureldien H. E. , Glinsky Gennadi V. , Sudha Thangirala , Mousa Shaker A. 
Published: January 2022

BackgroundAcute myeloid leukemia (AML) is associated with poor long-term survival, even with newer therapeutic agents. Here, we show the results of our preclinical study, in which we evaluated the efficacy of a new thyrointegrin αvβ3 antagonist, named fluorobenzyl polyethylene glycol conjugated tetraiodothyroacetic acid (fb-PMT).Methods and Resultsfb-PMT (NP751) is a potent αvβ3 antagonist of molecular weight of 2,478.9 Da. it represents a conjugate of tetraiodothyroacetic acid (tetrac) and monodisperse polyethylene glycol (PEG36), with a 4-fluorobenzyl group capping the other end of the PEG. fb-PMT effectively suppresses the malignant growth of human acute myeloid leukemia (AML) after successful engraftment in transgenic NSG-S xenograft mouse models of either established human AML cell line or primary AML cells. Daily treatment with fb-PMT (1–10 mg/kg body weight) subcutaneously (s.c.) for 3–4 weeks was associated with marked regression of leukemogenesis and extended survival in both models. The efficiency of the fb-PMT therapy was verified using in vivo imaging system (IVIS) imaging, flow cytometry, and histopathological examination to monitor the engraftment of leukemic cells in the bone marrow and other organs. fb-PMT therapy for 3–4 weeks at 3 and 10 mg/kg daily doses exhibited significant reduction (p &lt; 0.0001) of leukemic cell burden of 74% and &gt;95%, respectively. All fb-PMT-treated mice in the 10 mg/kg treatment arm successfully maintained remission after discontinuing the daily treatment. Comprehensive fb-PMT safety assessments demonstrated excellent safety and tolerability at multiple folds above the anticipated human therapeutic doses. Lastly, our genome-wide microarray screens demonstrated that fb-PMT works through the molecular interference mechanism with multiple signaling pathways contributing to growth and survival of leukemic cells.ConclusionOur preclinical findings of the potent anticancer activities of fb-PMT and its favorable safety profiles warrant its clinical investigation for the effective and safe management of AML.
Ten Years After SINS: Role of Surgery and Radiotherapy in the Management of Patients With Vertebral Metastases
Authors: Serratrice Nicolas , Faddoul Joe , Tarabay Bilal , Attieh Christian , Chalah Moussa A. , Ayache Samar S. , Abi Lahoud Georges N. 
Published: January 2022

The objective of the different types of treatments for a spinal metastasis is to provide the best oncological and functional result with the least aggressive side effects. Initially created in 2010 to help clinicians in the management of vertebral metastases, the Spine Instability Neoplastic Score (SINS) has quickly found its place in the decision making and the treatment of patients with metastatic spinal disease. Here we conduct a review of the literature describing the different changes that occurred with the SINS score in the last ten years. After a brief presentation of the spinal metastases’ distribution, with or without spinal cord compression, we present the utility of SINS in the radiological diagnosis and extension of the disease, in addition to its limits, especially for scores ranging between 7 and 12. We take this opportunity to expose the latest advances in surgery and radiotherapy concerning spinal metastases, as well as in palliative care and pain control. We also discuss the reliability of SINS amongst radiologists, radiation oncologists, spine surgeons and spine surgery trainees. Finally, we will present the new SINS-derived predictive scores, biomarkers and artificial intelligence algorithms that allow a multidisciplinary approach for the management of spinal metastases.
Differential Impact of Membrane-Bound and Soluble Forms of the Prognostic Marker Syndecan-1 on the Invasiveness, Migration, Apoptosis, and Proliferation of Cervical Cancer Cells
Authors: Hilgers Katharina , Ibrahim Sherif Abdelaziz , Kiesel Ludwig , Greve Burkhard , Espinoza-Sánchez Nancy A. , Götte Martin 
Published: January 2022

Cervical cancer ranks fourth among the most commonly diagnosed malignant tumors in women worldwide. Previously published evidence suggested a possible connection between the expression of the membrane-bound heparan sulfate proteoglycan syndecan-1 (Sdc-1) and the development of cervical carcinoma. Sdc-1 serves as a matrix receptor and coreceptor for receptor tyrosine kinases and additional signaling pathways. It influences cell proliferation, adhesion, and migration and is seen as a modulator of the tumor microenvironment. Following proteolytic cleavage of its extracellular domain in a process called shedding, Sdc-1 can act as a paracrine effector. The loss of Sdc-1 expression is associated with low differentiation of cervical carcinoma and with an increased rate of lymph node metastases. Here, we analyzed the clinical impact of Sdc-1 expression by analysis of public gene expression datasets and studied the effect of an overexpression of Sdc-1 and its membrane-bound and soluble forms on the malignant properties of the human cervical carcinoma cell line HeLa through functional analysis. For this purpose, the HeLa cells were stably transfected with the control plasmid pcDNA3.1 and three different Sdc-1-DNA constructs,encoding wild-type, permanently membrane-bound, and constitutively soluble Sdc-1. In clinical specimens, Sdc-1 mRNA was more highly expressed in local tumor tissues than in normal and metastatic cervical cancer tissues. Moreover, high Sdc-1 expression correlated with a poor prognosis in Kaplan-Meier survival analysis, suggesting the important role of Sdc-1 in the progression of this type of cancer. In vitro, we found that the soluble, as well as the permanently membrane-bound forms of Sdc-1 modulated the proliferation and the cell cycle, while membrane-bound Sdc1 regulated HeLa cell apoptosis. The overexpression of Sdc-1 and its soluble form increased invasiveness. In vitro scratch/wound healing assay, showed reduced Sdc-1-dependent cell motility which was linked to the Rho-GTPase signaling pathway. In conclusion, in cervical cancer Sdc-1 modulates pathogenetically relevant processes, which depend on the membrane-association of Sdc-1.