bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracerebral Injection of Graphene Oxide Nanosheets Mitigates Microglial Activation Without Inducing Acute Neurotoxicity: A Pilot Comparison to Other Nanomaterials
Authors: Portioli Corinne , Bussy Cyrill , Mazza Mariarosa , Lozano Neus , Jasim Dhifaf A. , Prato Maurizio , Bianco Alberto , Bentivoglio Marina , Kostarelos Kostas 
Published: November 2020

AbstractCarbon‐based nanomaterials (CNMs) are being explored for neurological applications. However, systematic in vivo studies investigating the effects of CNM nanocarriers in the brain and how brain cells respond to such nanomaterials are scarce. To address this, functionalized multiwalled carbon nanotubes and graphene oxide (GO) sheets are injected in mice brain and compared with charged liposomes. The induction of acute neuroinflammatory and neurotoxic effects locally and in brain structures distant from the injection site are assessed up to 1 week postadministration. While significant neuronal cell loss and sustained microglial cell activation are observed after injection of cationic liposomes, none of the tested CNMs induces either neurodegeneration or microglial activation. Among the candidate nanocarriers tested, GO sheets appear to elicit the least deleterious neuroinflammatory profile. At molecular level, GO induces moderate activation of proinflammatory markers compared to vehicle control. At histological level, brain response to GO is lower than after vehicle control injection, suggesting some capacity for GO to reduce the impact of stereotactic injection on brain. While these findings are encouraging and valuable in the selection and design of nanomaterial‐based brain delivery systems, they warrant further investigations to better understand the mechanisms underlying GO immunomodulatory properties in brain.
CCCDTD5: Individual and community‐based psychosocial and other non‐pharmacological interventions to support persons living with dementia and their caregivers
Authors: Vedel Isabelle , Sheets Debra , McAiney Carrie , Clare Linda , Brodaty Henry , Mann James , Anderson Nicole , Liu‐Ambrose Teresa , Rojas‐Rozo Laura , Loftus Lynn , Gauthier Serge , Sivananthan Saskia 
Published: November 2020

AbstractIntroductionCurrent pharmacological therapies for dementia have limited efficacy. Thus it is important to provide recommendations on individual and community‐based psychosocial and non‐pharmacological interventions for persons living with dementia (PLWDs) and their caregivers.MethodsPhase 1: A systematic review for developing recommendations on psychosocial and non‐pharmacological interventions at the individual and community level for PLWDs and their caregivers. Phase 2: Rating of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Phase 3: Delphi process (>50 dementia experts) for approving recommendations by the 5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5).ResultsThe CCCDTD5 approved the following recommendations: Exercise (1B) and group cognitive stimulation for PLWDs (2B), psychosocial and psychoeducational interventions for caregivers (2C), development of dementia friendly organization and communities (2C), and case management for PLWDs (2B).DiscussionThe CCCDTD5 provides for the first time, evidence‐based recommendations on psychosocial and non‐pharmacological interventions for PLWDs and their caregivers that can inform evidence‐based policies for PLWDs in Canada.
A review on RNAi therapy for NSCLC: Opportunities and challenges
Authors: Kumar Vignesh , Yadavilli Sairam , Kannan Raghuraman 
Published: November 2020

AbstractNon‐small cell lung cancer (NSCLC) is the primary cause of cancer death worldwide. Despite developments in chemotherapy and targeted therapies, the 5‐year survival rate has remained at approximately 16% for the last four decades. NSCLC is a heterogeneous group of tumors that, through mutations and drivers, also demonstrate intra‐tumor heterogeneity. Thus, current treatment approaches revolve around targeting these oncogenes, often using small molecule inhibitors and chemotherapeutics. However, the efficacy of these therapies has been crippled by acquired and inherent drug‐resistance in the tumor, accompanied by increased therapeutic dosages and subsequent devastating off‐target effects for patients. Evidently, there is a critical need for developing treatment methodologies more effective than the current standard of care. Fortunately, RNA interference, particularly small interfering RNA (siRNA), presents an alternative of silencing specific oncogenes to control tumor growth. Although siRNA therapy is subject to rapid degradation and poor internalization in vivo, nanoparticles can serve as nontoxic and efficient delivery vehicles, even introducing combinational delivery of multiple therapeutic agents. Indeed, siRNA‐nanoconstructs possess extraordinary potential as an innovative modality to address clinical needs. This state‐of‐the‐art review summarizes the recent advancements in the development of novel nanosystems for delivering siRNA to NSCLC tumors and analyzes the efficacy of representative examples. By illuminating the most promising biomarkers for silencing, we hope to streamline current therapeutic efforts and highlight powerful translational opportunities to combat NSCLC.This article is categorized under:
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Biology‐Inspired Nanomaterials > Lipid‐Based Structures
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
ADJUNCTION FOR VARIETIES WITH A ℂ* ACTION
Authors: ROMANO ELEONORA A. , WIŚNIEWSKI JAROSŁAW A. 
Published: November 2020

AbstractLet X be a complex projective manifold, L an ample line bundle on X, and assume that we have a ℂ* action on (X;L). We classify such triples (X; L;ℂ*) for which the closure of a general orbit of the ℂ* action is of degree ≤ 3 with respect to L and, in addition, the source and the sink of the action are isolated fixed points, and the ℂ* action on the normal bundle of every fixed point component has weights ±1. We treat this situation by relating it to the classical adjunction theory. As an application, we prove that contact Fano manifolds of dimension 11 and 13 are homogeneous if their group of automorphisms is reductive of rank ≥ 2.
Do you really want to deactivate your sacral neuromodulation device during pregnancy? A single center case series
Authors: Agnello Marco , Vottero Mario , Bertapelle Paola 
Published: November 2020

Abstract
Introduction and hypothesis
The main objective of the study is to assess the efficacy and safety of sacral neuromodulation (SNM) during pregnancy.

Methods
We retrospectively enrolled patients who underwent SNM implantation in our center and subsequently became pregnant. The indication for SNM, timing of device de-activation (if performed), course of pregnancy and urological complications, duration of labor, childbirth term, delivery mode, congenital abnormalities and SNM dysfunctions after delivery were recorded.

Results
Fourteen pregnancies were recorded among 11 women undergoing SNM. Indications for device implantation were urinary retention (7 cases) and dysfunctional voiding (4 cases). Two patients carried on two and three pregnancies, respectively, with the device turned off since the first trimester. They both had to return to self-catheterization and developed recurring urinary tract infections. No major urological complications were recorded among the remaining nine women that kept the device on during pregnancy. A cesarean section was performed in four cases for obstetric reasons, and in seven cases it was planned by the urologist and gynecologist to avoid lead damage/displacement. Three pregnancies resulted in a vaginal delivery, and no association with term of delivery or duration of labor was observed. No congenital abnormalities related to SNM or lead displacement are reported, and only one patient required device removal because of significant loss of efficacy after childbirth.

Conclusions
The use of SNM during pregnancy appears to be safe, without morbidity for the fetus. Moreover, risks associated with switching the device off may be greater than benefits and justify maintaining the electrical stimulation throughout pregnancy.
Optimal sampling strategies for darunavir and external validation of the underlying population pharmacokinetic model
Authors: Stillemans Gabriel , Belkhir Leila , Vandercam Bernard , Vincent Anne , Haufroid Vincent , Elens Laure 
Published: November 2020

Abstract
Purpose
A variety of diagnostic methods are available to validate the performance of population pharmacokinetic models. Internal validation, which applies these methods to the model building dataset and to additional data generated through Monte Carlo simulations, is often sufficient, but external validation, which requires a new dataset, is considered a more rigorous approach, especially if the model is to be used for predictive purposes. Our first objective was to validate a previously published population pharmacokinetic model of darunavir, an HIV protease inhibitor boosted with ritonavir or cobicistat. Our second objective was to use this model to derive optimal sampling strategies that maximize the amount of information collected with as few pharmacokinetic samples as possible.

Methods
A validation dataset comprising 164 sparsely sampled individuals using ritonavir-boosted darunavir was used for validation. Standard plots of predictions and residuals, NPDE, visual predictive check, and bootstrapping were applied to both the validation set and the combined learning/validation set in NONMEM to assess model performance. D-optimal designs for darunavir were then calculated in PopED and further evaluated in NONMEM through simulations.

Results
External validation confirmed model robustness and accuracy in most scenarios but also highlighted several limitations. The best one-, two-, and three-point sampling strategies were determined to be pre-dose (0 h); 0 and 4 h; and 1, 4, and 19 h, respectively. A combination of samples at 0, 1, and 4 h was comparable to the optimal three-point strategy. These could be used to reliably estimate individual pharmacokinetic parameters, although with fewer samples, precision decreased and the number of outliers increased significantly.

Conclusions
Optimal sampling strategies derived from this model could be used in clinical practice to enhance therapeutic drug monitoring or to conduct additional pharmacokinetic studies.
Outcomes of Laparoscopic Splenectomy for Treatment of Splenomegaly: A Systematic Review and Meta‐analysis
Authors: Rodríguez‐Luna María Rita , Balagué Carmen , Fernández‐Ananín Sonia , Vilallonga Ramon , Targarona Soler Eduardo María 
Published: November 2020

AbstractObjectivesTo review the evidence regarding the outcomes of laparoscopic techniques in cases of splenomegaly.BackgroundEndoscopic approaches such as laparoscopic, hand‐assisted laparoscopic, and robotic surgery are commonly used for splenectomy, but the advantages in cases of splenomegaly are controversial.Review methodsWe conducted a systematic review using PRISMA guidelines. PubMed/MEDLINE, ScienceDirect, Scopus, Cochrane Library, and Web of Science were searched up to February 2020.ResultsNineteen studies were included for meta‐analysis. In relation to laparoscopic splenectomy (LS) versus open splenectomy (OS), 12 studies revealed a significant reduction in length of hospital stay (LOS) of 3.3 days (p = <0.01) in the LS subgroup. Operative time was higher by 44.4 min (p < 0.01) in the LS group. Blood loss was higher in OS 146.2 cc (p = <0.01). No differences were found regarding morbimortality. The global conversion rate was 19.56%. Five studies compared LS and hand‐assisted laparosocpic splenectomy (HALS), but no differences were observed in LOS, blood loss, or complications. HALS had a significantly reduced conversion rate (p < 0.01). In two studies that compared HALS and OS (n = 66), HALS showed a decrease in LOS of 4.5 days (p < 0.01) and increase of 44 min in operative time (p < 0.01), while OS had a significantly higher blood loss of 448 cc (p = 0.01). No differences were found in the complication rate.ConclusionLS is a safe approach for splenomegaly, with clear clinical benefits. HALS has a lower conversion rate. Higher‐quality confirmatory trials with standardized splenomegaly grading are needed before definitive recommendations can be provided.Prospero registration number: CRD42019125251.
Development of image quality related reference doses called acceptable quality doses (AQD) in paediatric CT exams in Qatar
Authors: Kharita Mohammad Hassan , AlNaemi Huda , Kini Vishwanatha , Alkhazzam Shady , Rehani Madan M. 
Published: November 2020

Abstract
Objectives
To describe first experience of integrating assessment of image quality in paediatric X-ray computed tomography (CT) with analysis of the radiation dose indices to develop reference doses called acceptable quality dose (AQD).

Methods
Image quality was scored by the radiologists at a tertiary care hospital in Qatar on a scale of 0 to 4 using the recently published scoring criteria. The patients undergoing head, chest and abdomen CT were divided in different weight groups as follows: < 5 kg, 5–< 15 kg, 15–< 30 kg, 30–< 50 kg, 50–< 80 kg and > 80 kg. The images that were clinically acceptable (score of 3) were included for assessment of median values of CTDIvol and DLP to obtain AQDs in different weight groups.

Results
After initial training in image quality scoring of CT images of 49 patients by three radiologists, the study on 715 patients indicated 665 studies (93%) were clinically acceptable as per scoring criteria. The median CTDIvol values for the above weight groups were 16, 20, 22, 22, 27 and 27 mGy and the median DLP values for these weight groups were 271, 377, 463, 486, 568 and 570 mGy cm, respectively, for head CT. Similar values are presented for chest and abdomen CTs.

Conclusions
The first ever experience of starting with image quality assessment and integrating it with analysis of dose indices to obtain AQD values shall provide a workable model for others and values for comparison within the facility and in other facilities leading to optimisation.

Key Points
• The first study to integrate image quality assessment with analysis of patient dose indices shows feasibility for routine practice in other centres.
• The values of acceptable quality dose (AQD) were provided for head, chest and abdomen CT of children divided into weight groups rather than age. They shall act as reference values for future studies.
• Verification of our findings on proportional increase in exposure parameters (CTDIvol and DLP) with weight by other investigators shall be helpful.
Extension of WRF-Chem for birch pollen modelling—a case study for Poland
Authors: Werner Małgorzata , Guzikowski Jakub , Kryza Maciej , Malkiewicz Małgorzata , Bilińska Daria , Skjøth Carsten Ambelas , Rapiejko Piotr , Chłopek Kazimiera , Dąbrowska-Zapart Katarzyna , Lipiec Agnieszka , Jurkiewicz Dariusz , Kalinowska Ewa , Majkowska-Wojciechowska Barbara , Myszkowska Dorota , Piotrowska-Weryszko Krystyna , Puc Małgorzata , Rapiejko Anna , Siergiejko Grzegorz , Weryszko-Chmielewska Elżbieta , Wieczorkiewicz Andrzej , Ziemianin Monika 
Published: November 2020

AbstractIn recent years, allergies due to airborne pollen allergens have shown an increasing trend, along with the severity of allergic symptoms in most industrialized countries, while synergism with other common atmospheric pollutants has also been identified as affecting the overall quality of citizenly life. In this study, we propose the state-of-the-art WRF-Chem model, which is a complex Eulerian meteorological model integrated on-line with atmospheric chemistry. We used a combination of the WRF-Chem extended towards birch pollen, and the emission module based on heating degree days, which has not been tested before. The simulations were run for the moderate season in terms of birch pollen concentrations (year 2015) and high season (year 2016) over Central Europe, which were validated against 11 observational stations located in Poland. The results show that there is a big difference in the model’s performance for the two modelled years. In general, the model overestimates birch pollen concentrations for the moderate season and highly underestimates birch pollen concentrations for the year 2016. The model was able to predict birch pollen concentrations for first allergy symptoms (above 20 pollen m−3) as well as for severe symptoms (above 90 pollen m−3) with probability of detection at 0.78 and 0.68 and success ratio at 0.75 and 0.57, respectively for the year 2015. However, the model failed to reproduce these parameters for the year 2016. The results indicate the potential role of correcting the total seasonal pollen emission in improving the model’s performance, especially for specific years in terms of pollen productivity. The application of chemical transport models such as WRF-Chem for pollen modelling provides a great opportunity for simultaneous simulations of chemical air pollution and allergic pollen with one goal, which is a step forward for studying and understanding the co-exposure of these particles in the air.
Neuromodulation of the subthalamic nucleus in Parkinson’s disease: the effect of fiber tract stimulation on tremor control
Authors: Abdulbaki Arif , Kaufmann Jörn , Galazky Imke , Buentjen Lars , Voges Jürgen 
Published: November 2020

Abstract
Background
Therapeutic effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD) may in parts be attributed to the stimulation of white matter near the targeted structure. The dentato-rubro-thalamic (DRT) tract supposed to improve tremor control in patients with essential tremor could be one candidate structure. The aim of this study was to investigate the effect of stimulation proximity to the DRT on tremor control in PD patients treated with STN-DBS.

Methods
For this retrospective analysis, we included 36 consecutive patients (median age 65.5 years) treated with STN-DBS for disabling motor symptoms including tremor. Stereotactic implantation of DBS electrodes into the motor area of the STN was performed using direct MRI-based targeting and intraoperative microelectrode recording. Tremor severity was assessed preoperatively and at regular intervals postoperatively (Unified Parkinson’s Disease Rating Scale III). The DRT was visualized in 60 hemispheres after probabilistic fiber tracking (3-T MRI). The position of active electrode contacts was verified on intraoperative stereotactic X-rays and postoperative CT images after co-registration with 3D treatment planning MRI/CT images. We determined the shortest distance of active contacts to the ipsilateral DRT tracts on perpendicular view slices and correlated this value with tremor change percentage.

Results
Twelve patients had unilateral tremor only, and accordingly, 12 hemispheres were excluded from further imaging analysis. The remaining 60 hemispheres were associated with contralateral resting tremor. Active brain electrode contacts leading to resting tremor improvement (46 hemispheres) had a significantly shorter distance to the DRT (1.6 mm (0.9–2.1) [median (25th–75th percentiles)]) compared with contacts of non-responders (14 hemispheres, distance: 2.8 mm (2–4.6), p < 0.001).

Conclusion
This retrospective analysis suggests that in STN-DBS, better tremor control in PD patients correlates with the distance of active electrode contacts to the DRT. Tractography may optimize both individually DBS targeting and postoperative adjustment of stimulation parameters.
Plasma free amino acid profiling as metabolomic diagnostic and prognostic biomarker in paediatric cancer patients: a follow-up study
Authors: Synakiewicz Anna , Stanislawska-Sachadyn Anna , Sawicka-Zukowska Malgorzata , Galezowska Grazyna , Ratajczyk Joanna , Owczarzak Anna , Skuza Malgorzata , Wolska Lidia , Stachowicz-Stencel Teresa 
Published: November 2020

AbstractAmino acids (AAs) play a crucial role in cancer cell metabolism. Levels of 22 plasma AAs at the time of diagnosis and after treatment were established among 39 pediatric cancer patients and 33 healthy children. Glutamic acid levels decreased and tryptophan levels increased during treatment. Cancer patients presented significantly lower levels of glutamine and leucine post-treatment while levels of 12 other AAs were higher comparing to controls. Results suggest that plasma free AA profile may serve as a prognostic biomarker.
Saliva substitute mouthwash in nasopharyngeal cancer survivors with xerostomia: a randomized controlled trial
Authors: Marimuthu Dayaabaran , Han Kong Min , Mohamad Mohd Shawal Firdaus , Azman Mawaddah 
Published: November 2020

AbstractObjectivesXerostomia is a prevalent sequelae among nasopharyngeal cancer (NPC) survivors; yet, effective treatment protocols have been elusive. This study was a prospective randomized clinical trial to compare the effects of saliva substitute mouthwash in nasopharyngeal cancer survivors with xerostomia, between two treatment arms, conducted in a tertiary center.Materials and methodsThis study measured the effects within 4 weeks in relation to summated xerostomia inventory (SXI) and unstimulated whole saliva (UWS). Patients randomized into the interventional arm were prescribed an immunologically active saliva substitute (IASS), while patients in the control arm were prescribed a non-immunologically active mouthwash as placebo.ResultsThe study population consisted of 94 patients. There was a significant difference in SXI difference (p< 0.0001) and UWS difference (p< 0.0001) between control and interventional arms. No harmful side effects associated with the use of either mouthwash encountered throughout the study duration.ConclusionIASS mouthwash significantly reduces subjective xerostomia scores measured using SXI and improves objective measurement of salivary flow using UWS among nasopharyngeal cancer survivors with xerostomia.Clinical relevanceIASS is significantly more effective in improving subjective and objective xerostomia measurements compared to non-immunologically active mouthwash. Additionally, this treatment is very safe, with superior side effect profiles.Trial registrationClinicalTrials.govIdentifier: NCT04491435
Allergenic fungal spores in the air of urban parks
Authors: Kasprzyk Idalia , Grinn-Gofroń Agnieszka , Ćwik Agata , Kluska Katarzyna , Cariñanos Paloma , Wójcik Tomasz 
Published: November 2020

AbstractUrban green spaces, especially urban parks, are essential for the proper functioning of cities, but they can be a serious source of airborne fungal spores. Aerobiological monitoring was carried out in urban parks of different typology to estimate the risk associated with fungal spores for citizens. Volumetric method was applied with the use of portable Burkard Sampler. In the air of the studied parks, the most dominant spores are strong allergenic or considered as potentially allergenic. Cladosporium spores were found in enormous concentrations in all studied parks, and it affected the low biodiversity of fungal spores in the parks. Compared to Cladosporium, concentrations of Alternaria spores in the air were several dozen times lower, but still a risk for people who are allergic. The fungal spores spectra and their seasonal occurrence in each park were similar. The highest similarities in the patterns of the season were found in the case of Cladosporium, Alternaria, Epicoccum, and the lowest in the case of Torula and Drechslera type. Due to the fact that allergy sufferers are most often polysensitized, the period when they should limit long visits in the urban parks is July–August, when the concentration of allergenic fungal spores of many taxa is the highest.