bluuebunny/crossref_metadata_2025_split huggingface dataset:
An artificial neural network model for prediction of hypoxemia during sedation for gastrointestinal endoscopy
Authors: Geng Wujun , Tang Hongli , Sharma Apurb , Zhao Yizhou , Yan Ye , Hong Wandong 
Published: March 2019

Objective This study was designed to assess clinical predictors of hypoxemia and develop an artificial neural network (ANN) model for prediction of hypoxemia during sedation for gastrointestinal endoscopy examination. Methods A total of 220 patients were enrolled in this prospective observational study. Data on demographics, chronic concomitant disease information, neck circumference, thyromental distance and anaesthetic dose were collected and statistically analysed. Results Univariate analysis indicated that body mass index (BMI), habitual snoring and neck circumference were associated with hypoxemia. An ANN model was developed with three variables (BMI, habitual snoring and neck circumference). The area under the receiver operating characteristic curve for the ANN model was 0.80. Conclusions The ANN model developed here, comprising BMI, habitual snoring and neck circumference, was useful for prediction of hypoxemia during sedation for gastrointestinal endoscopy.
Interobserver variability (between radiation oncologist and radiation therapist) in tumor bed contouring after breast-conserving surgery
Authors: La Rocca Eliana , Lici Vanessa , Giandini Tommaso , Bonfantini Francesca , Frasca Sarah , Dispinzieri Michela , Gennaro Massimiliano , Di Cosimo Serena , Lozza Laura , Pignoli Emanuele , Valdagni Riccardo , De Santis Maria Carmen 
Published: March 2019

Purpose: To examine interobserver variability between the radiation oncologist (RTO) and the radiation therapist (RTT) in delineating the tumor bed (TB) in early breast cancer (BC). Methods: We retrospectively analyzed patients who received a radiotherapy boost to the TB. In a first group, the clinical target volume (CTV) for the boost was the surgical bed, defined by using surgical clips. In a second group, the CTV was defined by identifying a seroma cavity or a metallic find on the scar. These contours were compared in terms of volume, number of slices, and Dice similarity coefficient (DSC). Results: Forty patients were assessed: 20 had surgical clips (group 1) while the other 20 had none (group 2). There was no difference in the number of slices contoured by the 2 operators for group 1, but a statistically significant difference emerged in the volumes: the RTT identified a TB that was a mean 45% smaller than the one identified by the RTO. Random differences were found between the 2 operators for group 2. The TBs delineated for this group were significantly larger ( P<0.05) than those identified by the RTT for group 1. The mean Dice value between the RTO’s and the RTT’s TBs was 0.69±0.07 (range 0.53–0.81) for group 1 and 0.37±0.18 (range 0–0.58) for group 2 ( P<0.05). Conclusions: This study showed that the use of clips coincided with less interoperator variability. With appropriate training, the RTT may play an important part in the multidisciplinary radiotherapy team.
Asbestos fiber identification in liver from cholangiocarcinoma patients living in an asbestos polluted area: a preliminary study
Authors: Grosso Federica , Croce Alessandro , Libener Roberta , Mariani Narciso , Pastormerlo Massimo , Maconi Antonio , Rinaudo Caterina 
Published: March 2019

Purpose: To assess whether asbestos fibers may be observed in liver tissue of patients with cholangiocarcinoma (CC) with environmental or working asbestos exposure. Methods: Detection of fibers was performed directly on histologic sections of liver from 7 patients with CC using optical microscope and variable pressure scanning electron microscopy equipped with energy-dispersive spectroscopy (VP-SEM/EDS). All patients were from Casale Monferrato, Italy, a highly asbestos-polluted town. Due to ethical constraints, observers were blinded to patients’ clinical features. Results: Fibers/bundles of fibers of chrysotile were detected in 5 out of 7 patients (71%). The boundary between healthy and neoplastic tissue or the fibrocollagen tissue produced by the neoplasia were identified as areas of fiber incorporation. Conclusions: This study is the first report about the detection of chrysotile asbestos fibers in the liver of patients with CC. Further studies on larger cohorts are needed to corroborate our preliminary findings.
Differences in fibertract profiles between patients with migraine and those with persistent post-traumatic headache
Authors: Chong Catherine D , Peplinski Jacob , Berisha Visar , Ross Katherine , Schwedt Todd J 
Published: March 2019

Objectives Often, persistent post-traumatic headache and migraine are phenotypically similar. However, the similarities and differences in the neuropathological underpinnings of persistent post-traumatic headache and migraine require further understanding. We used diffusion tensor imaging (DTI) and a novel method for detecting subtle changes in fibertract integrity by measuring node-by-node parameters along each tract to compare fibertract profiles between those with migraine and those with persistent post-traumatic headache, and compared both cohorts to a group of controls. Methods Eighteen fibertracts were reconstructed for 131 subjects, including 49 patients with persistent post-traumatic headache attributed to mild traumatic brain injury, 41 with migraine, and 41 controls. Node-by-node diffusion parameters of mean diffusivity and radial diffusivity were calculated along each tract. Mean diffusivity and radial diffusivity measurements were averaged along quartiles of each tract for statistical interpretation and group comparison. Using a post-hoc analysis, correlations between tract quartile measurements and headache frequency were calculated. Results There were significant differences between migraine and persistent post-traumatic headache cohorts for quartile measurements of mean diffusivity or radial diffusivity in the bilateral anterior thalamic radiations, cingulum (angular bundles and cingulate gyri), inferior longitudinal fasciculi, and uncinate fasciculi, the left corticospinal tract, and the right superior longitudinal fasciculi-parietal portion. For migraine patients, there was a significant positive correlation between headache frequency and forceps major mean diffusivity, whereas for persistent post-traumatic headache there was a positive correlation between headache frequency and cingulum angular bundle mean diffusivity and radial diffusivity. Conclusions Quartile measurements of radial diffusivity and mean diffusivity indicate unique differences in fibertract profiles between those with migraine vs. persistent post-traumatic headache. Although for both migraine and persistent post-traumatic headache there was a positive relationship between fibertract alterations and headache frequency, there were disease-specific differences between headache frequency and fibertract injury patterns. These findings might suggest potential differences in the neuropathological mechanisms underlying migraine and persistent post-traumatic headache.
The spectrum of cluster headache: A case report of 4600 attacks
Authors: Hagedorn Andreas , Snoer Agneta , Jensen Rigmor , Haddock Bryan , Barloese Mads 
Published: March 2019

Introduction Knowledge of the clinical features of cluster headache is mainly based on retrospective and cross-sectional studies. Here, we present a case of a chronic cluster headache patient who prospectively recorded timing and clinical features of all attacks for 6 years, aiming to describe the clinical spectrum and timing of cluster headache symptoms experienced and to identify daily and/or seasonal rhythmicity. Methods Registration of attack timing, duration, associated symptoms and severity was done prospectively on a smartphone application. Pain severity was recorded on a 0–10 scale. Attacks were divided into mild, moderate, severe, and very severe. We analysed diurnal rhythmicity by multimodal Gaussian analysis and spectral analysis. Results In total, 4600 attacks were registered (mean duration 39.3 (SD 18.5) min. Mean severity 3.6 (SD 1.28)). Mild attacks accounted for 14.2%, moderate 65.7%, severe 16.9% and very severe 3.2% of all attacks. Nocturnal attacks were more severe than daytime attacks. The number of autonomic symptoms and duration of attacks increased with pain severity. Peak chronorisk (risk of attacks occurring according to hour of day) was at 12.48 in the registration period. Over time, circadian rhythmicity and attack frequency varied. Conclusion Clinical characteristics of cluster headache attacks can vary greatly within the individual patient. Clinicians attempting to personalise the administration of preventive treatment should pay notice to the variation over time in diurnal rhythmicity. The recorded self-limiting mild attacks that do not fulfill the ICHD-3 criteria for a cluster headache attack warrant further investigation, as they could hold important information about disease activity.
Evaluation of the Effects of Clobazam on Seizure Control and Quality of Life in Children With Lennox-Gastaut Syndrome: A Pilot Study
Authors: Weinstock Arie , Agarwal Nitin , Farooq Osman , Cheema Zaheer , Hamilton Deanna , Parrish Joy 
Published: March 2019

Purpose: This is a prospective study of children with Lennox-Gastaut syndrome receiving clobazam as adjunctive therapy. This pilot study aims to examine medication effectiveness as it relates to seizure reduction, as well as improvement in parent-reported behavior and quality of life (QOL). Methods: Ten patients with Lennox-Gastaut syndrome aged 3-11 years were enrolled in this 6-week, 4 phase study. Seizure frequency, QOL, and Aberrant Behavior Checklist questionnaires were evaluated at 0, 2, 6, and 10 weeks during the study. Results: Patients showed improvement on indices of QOL, including physical activities (62.5%), well-being (37.5%), cognition (87.5%), social activities (37.5%), behavior (87.5%), general health (50%), and overall QOL (87.5%). The Quality of Life in Childhood Epilepsy (QOLCE) questionnaire revealed significant improvement in cognition ( P = .008), social activities ( P = .049), behavior ( P = .038), and overall QOL ( P = .018). The Aberrant Behavior Checklist exhibited a trend toward improvement in hyperactivity. Conclusion: There was improvement in all patients with documented baseline seizures (8/10), with 5 showing significant improvement (95%-100% reduction) and 3 showing minor improvement (7%-23% reduction). Statistically significant improvement in areas of cognition, social activities, behavior, and overall QOL were seen. An overall trend toward a positive well-being was seen in our patients with clobazam, as adjunct therapy for Lennox-Gastaut syndrome in children.
Serum Cortisol as an Early Biomarker of Cardiopulmonary Parameters Within the First 24 Hours After Aneurysmal Subarachnoid Hemorrhage in Intensive Care Unit Patients
Authors: Bender Michael , Stein M. , Uhl E. , Reinges M. H. T. 
Published: March 2019

Objective: Cardiopulmonary complications/stress are well-known phenomena in patients after aneurysmal subarachnoid hemorrhage (aSAH) and might be associated with an elevated serum troponin I (TNI) level. Since the glucocorticoid hormone cortisol is released during stress situations, the present study was conducted to investigate the influence of serum cortisol (SC) on cardiac and pulmonary parameters in patients after aSAH within the first 24 hours of intensive care unit (ICU) treatment. Patients and Methods: We retrospectively analyzed a cohort of 104 patients with aSAH admitted to our emergency department between January 2008 and April 2017. Blood samples were taken to determine SC and TNI. Demographics, initial Glasgow Coma Scale (GCS) score, World Federation of Neurosurgical Societies (WFNS) score, and Fisher grade were evaluated retrospectively. Mean norepinephrine application rate (NAR) in µg/kg/min and mean inspiratory oxygen fraction (OF) within the first 24 hours were defined as cardiopulmonary parameters. Results: An elevated SC value was found in 44 (42%) patients, and 27 (26%) patients showed an increased TNI value. In patients with initially increased SC value, a significant higher NAR ( P = .04) was needed. Furthermore, patients with initially elevated TNI value had a lower GCS score ( P = .0013) and a higher WFNS score ( P = .003) on admission and required a higher NAR ( P = .02) as well as OF ( P = .0008) within the first 24 hours of ICU treatment. Conclusions: In the current study, initially elevated SC values were associated with a higher need of NAR within the first 24 hours of ICU treatment after aSAH. Moreover, patients with initially elevated TNI values required an increased NAR and a higher OF so that these biomarkers could be useful to improve ICU treatment.
Association Between CSF Beta-Amyloid and Apathy in Early-Stage Alzheimer Disease
Authors: Vergallo A. , Giampietri L. , Pagni C. , Giorgi F. S. , Nicoletti V. , Miccoli M. , Libertini P. , Petrozzi L. , Bonuccelli U. , Tognoni G. 
Published: March 2019

Aim: The apathetic syndrome is a common clinical feature in patients with Alzheimer diseases (AD), from preclinical phases to late stages of dementia, and it is strongly related to major disease outcomes. Unfortunately, no specific pharmacological treatments for apathy have been accomplished so far. Translational evidences have previously shown that a link between apathy and hallmarks of AD-related pathophysiology, that is, β-amyloid (Aβ) plaques and neurofibrillary tangles, exists. However, only few studies investigated the association between core biomarkers of AD and apathy scores, finding conflicting results. Methods: Thirty-seven patients were identified as having AD dementia according to National Institute on Aging–Alzheimer Association 2011 criteria. All participants underwent an extensive diagnostic workup including cerebrospinal fluid (CSF) assessment to measure the concentrations of Aβ42, t-tau, and pTau181. To follow, they were stratified as: apathy absence, apathy mild, and apathy severe according to the Neuro Psychiatric Inventory-apathy item scores. We investigated for potential associations between apathy scores and CSF biomarkers concentrations as well as for differences in terms of clinical and CSF biomarkers data across the 3 apathy groups. Results: The CSF Aβ42 concentrations were negatively correlated with apathy scores. In addition, patients with severe apathy had significantly lower Aβ42 levels compared to nonapathetic ones. Conclusion: Based on our results, we encourage further studies to untangle the potential association between the complex pathophysiological dynamics of AD and apathy which may represent an innovative reliable clinical outcome measure to use in clinical trials, investigating treatments with either a symptomatic or a disease-modifying effect.
Longer Operative Time Is Independently Associated With Surgical Site Infection and Wound Dehiscence Following Open Reduction and Internal Fixation of the Ankle
Authors: Gowd Anirudh K. , Bohl Daniel D. , Hamid Kamran S. , Lee Simon , Holmes George B. , Lin Johnny 
Published: March 2019

Background: Little is known regarding the association of operative time with adverse events following foot and ankle surgery. This study tests whether greater operative time is associated with the occurrence of adverse events following open reduction and internal fixation (ORIF) of the ankle. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for cases of ankle ORIF (primary CPT codes 27766, 27769, 27792, 27814, 27822, 27823) performed during 2005-2016. Operative time was tested for association with the occurrence of adverse events with controls for baseline characteristics and primary CPT code. Results: A total of 20 591 procedures met inclusion/exclusion criteria. The average (±SD) operative time was 75.7 (±37.3) minutes and varied by baseline characteristics and primary CPT code. After controlling for these factors, a 15-minute increase in operative time was associated with an 11% increase in risk for developing surgical site infection (SSI; relative risk [RR]: 1.11; 95% CI: 1.06-1.16), 20% for wound dehiscence (RR: 1.20; 95% CI: 1.11-1.29), 10% for anemia requiring transfusion (RR: 1.10; 95% CI: 1.04-1.17), 60% for cerebrovascular accident (RR: 1.60; 95% CI: 1.17-2.18), 14% for unplanned intubation (RR: 1.14; 95% CI: 1.03-1.26), and 7% for extended length of hospital admission (RR: 1.07; 95% CI: 1.05-1.09). Conclusion: Operative time is linearly and independently associated with the risks for SSI, wound dehiscence, and other adverse events following ORIF of the ankle. Efforts should be implemented to safely minimize operative duration without compromising the technical components of the procedure. Levels of Evidence: Therapeutic, Level IV
The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells
Authors: Miyagi Satoru , Sroczynska Patrycja , Kato Yuko , Nakajima-Takagi Yaeko , Oshima Motohiko , Rizq Ola , Takayama Naoya , Saraya Atsunori , Mizuno Seiya , Sugiyama Fumihiro , Takahashi Satoru , Matsuzaki Yumi , Christensen Jesper , Helin Kristian , Iwama Atsushi 
Published: March 2019

Abstract
Recurrent inactivating mutations have been identified in the X-linked plant homeodomain finger protein 6 (PHF6) gene, encoding a chromatin-binding transcriptional regulator protein, in various hematological malignancies. However, the role of PHF6 in normal hematopoiesis and its tumor-suppressor function remain largely unknown. We herein generated mice carrying a floxed Phf6 allele and inactivated Phf6 in hematopoietic cells at various developmental stages. The Phf6 deletion in embryos augmented the capacity of hematopoietic stem cells (HSCs) to proliferate in cultures and reconstitute hematopoiesis in recipient mice. The Phf6 deletion in neonates and adults revealed that cycling HSCs readily acquired an advantage in competitive repopulation upon the Phf6 deletion, whereas dormant HSCs only did so after serial transplantations. Phf6-deficient HSCs maintained an enhanced repopulating capacity during serial transplantations; however, they did not induce any hematological malignancies. Mechanistically, Phf6 directly and indirectly activated downstream effectors in tumor necrosis factor α (TNFα) signaling. The Phf6 deletion repressed the expression of a set of genes associated with TNFα signaling, thereby conferring resistance against the TNFα-mediated growth inhibition on HSCs. Collectively, these results not only define Phf6 as a novel negative regulator of HSC self-renewal, implicating inactivating PHF6 mutations in the pathogenesis of hematological malignancies, but also indicate that a Phf6 deficiency alone is not sufficient to induce hematopoietic transformation.
Delivery of oncolytic vaccinia virus by matched allogeneic stem cells overcomes critical innate and adaptive immune barriers
Authors: Draganov Dobrin D. , Santidrian Antonio F. , Minev Ivelina , Nguyen Duong , Kilinc Mehmet Okyay , Petrov Ivan , Vyalkova Anna , Lander Elliot , Berman Mark , Minev Boris , Szalay Aladar A. 
Published: March 2019

Abstract
Background
Previous studies have identified IFNγ as an important early barrier to oncolytic viruses including vaccinia. The existing innate and adaptive immune barriers restricting oncolytic virotherapy, however, can be overcome using autologous or allogeneic mesenchymal stem cells as carrier cells with unique immunosuppressive properties.

Methods
To test the ability of mesenchymal stem cells to overcome innate and adaptive immune barriers and to successfully deliver oncolytic vaccinia virus to tumor cells, we performed flow cytometry and virus plaque assay analysis of ex vivo co-cultures of stem cells infected with vaccinia virus in the presence of peripheral blood mononuclear cells from healthy donors. Comparative analysis was performed to establish statistically significant correlations and to evaluate the effect of stem cells on the activity of key immune cell populations.

Results
Here, we demonstrate that adipose-derived stem cells (ADSCs) have the potential to eradicate resistant tumor cells through a combination of potent virus amplification and sensitization of the tumor cells to virus infection. Moreover, the ADSCs demonstrate ability to function as a virus-amplifying Trojan horse in the presence of both autologous and allogeneic human PBMCs, which can be linked to the intrinsic immunosuppressive properties of stem cells and their unique potential to overcome innate and adaptive immune barriers. The clinical application of ready-to-use ex vivo expanded allogeneic stem cell lines, however, appears significantly restricted by patient-specific allogeneic differences associated with the induction of potent anti-stem cell cytotoxic and IFNγ responses. These allogeneic responses originate from both innate (NK)- and adaptive (T)- immune cells and might compromise therapeutic efficacy through direct elimination of the stem cells or the induction of an anti-viral state, which can block the potential of the Trojan horse to amplify and deliver vaccinia virus to the tumor.

Conclusions
Overall, our findings and data indicate the feasibility to establish simple and informative assays that capture critically important patient-specific differences in the immune responses to the virus and stem cells, which allows for proper patient-stem cell matching and enables the effective use of off-the-shelf allogeneic cell-based delivery platforms, thus providing a more practical and commercially viable alternative to the autologous stem cell approach.
Ewing Sarcoma in Nepal Treated With Combined Chemotherapy and Definitive Radiotherapy
Authors: Jha Anjani Kumar , Neupane Pradeep , Pradhan Manohar , Sharma Krishna Sagar , Shrestha Sadina , Sigdel Padma Raj , Smeland Sigbjørn , Bruland Øyvind S. 
Published: March 2019

PURPOSE To our knowledge, we conducted the first prospective oncologic clinical trial in Nepal aimed at providing state-of-the-art chemotherapy to patients with Ewing sarcoma. The efficacy of external-beam radiotherapy (RT) as the sole local treatment modality was explored and deemed justified as a result of the lack of available advanced tumor-orthopedic services in Nepal. PATIENTS AND METHODS Twenty patients, 11 female and 9 male patients between the ages of 6 and 37 years, with newly diagnosed Ewing sarcoma were enrolled. Neoadjuvant combination chemotherapy, comprising well-established drug combinations, was administered in five courses before external-beam RT, during which one course of etoposide and ifosfamide was given. After RT, six additional chemotherapy courses were scheduled. RESULTS RT was tolerated well, providing rapid symptom relief and local tumor control, with no pathologic fractures observed among the 15 patients who received such treatment. Eleven patients completed the entire treatment protocol; seven patients were under continued follow-up, with no evidence of disease in six patients at a median follow-up time of 2.3 years (range, 1.3 to 3.1 years) and one patient alive but with a regional recurrence. Four patients experienced metastatic relapse and died as a result of their disease. Three treatment-related deaths linked to toxicity from chemotherapy occurred. Four of the six patients who refused to complete the treatment protocol and were lost to follow-up experienced progressive disease and were assumed dead. CONCLUSION This study was feasible with RT as the sole local treatment modality in combination with chemotherapy. As a result of the high number of patients lost to follow-up, no firm conclusions can be drawn, but the majority of the patients who completed treatment obtained durable long-term remissions.