bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conjunctival Microbiota in Patients With Type 2 Diabetes Mellitus and Influences of Perioperative Use of Topical Levofloxacin in Ocular Surgery
Authors: Zhu Xiangjia , Wei Ling , Rong Xianfang , Zhang Yinglei , Zhang Qian , Wen Xiaofeng , He Wenwen , Zhang Keke , Chen Feng , Wei Lai , Lu Yi 
Published: April 2021

Background: Patients with type 2 diabetes mellitus (T2DM) are prone to ocular surface infections. We therefore characterized the conjunctival microbiome of T2DM patients and the influence of topical levofloxacin to investigate whether a dysbiosis is associated with this phenomenon.Methods: Conjunctival microbiome of 79 T2DM patients and 113 non-diabetic controls was profiled using the 16S rDNA sequencing approach. Furthermore, 21 T2DM and 14 non-diabetic patients who underwent cataract surgeries were followed up perioperatively and the influence of pre- and post-operative levofloxacin on the conjunctival microbiome was further investigated prospectively and compared longitudinally.Results: The α-diversity of the conjunctival microbiota was significantly higher in T2DM patients than in controls (P &lt; 0.05). Significant differences in both composition and function of the conjunctival microbiome were identified on the ocular surface of T2DM patients as compared to non-diabetic controls. Particularly, phylum Bacteroidetes and Fusobacteria, genus Pseudomonas, Haemophilus, and Empedobacter were enriched, while genus Streptococcus was reduced on the T2DM ocular surface. Microbial genes functioning of bacterial chemotaxis was elevated in the conjunctival microbiome of T2DM patients. Furthermore, compared to the initial status, several genera including Staphylococcus were more abundant in the conjunctival microbiome of T2DM patients after 3-days use of preoperative levofloxacin topically, while no genus was more abundant in the non-diabetic follow-up group. No difference was observed between initial status and 7 days after ceasing all postoperative medications in both diabetic and non-diabetic follow-up groups.Conclusions: The conjunctival microbiome of T2DM patients was more complex and may respond differently to topical antibiotics.
Alterations of Phagocytic Activity and Capacity in Granulocytes and Monocytes Depend on the Pathogen Strain in Porcine Polytrauma
Authors: Vollrath Jan Tilmann , Klingebiel Felix , Bläsius Felix Marius , Greven Johannes , Bolierakis Eftychios , Janicova Andrea , Dunay Ildiko Rita , Hildebrand Frank , Marzi Ingo , Relja Borna 
Published: April 2021

Background: Polytraumatized patients undergo a strong immunological stress upon insult. Phagocytes (granulocytes and monocytes) play a substantial role in immunological defense against bacteria, fungi and yeast, and in the clearance of cellular debris after tissue injury. We have reported a reduced monocytes phagocytic activity early after porcine polytrauma before. However, it is unknown if both phagocyte types undergo those functional alterations, and if there is a pathogen-specific phagocytic behavior. We characterized the phagocytic activity and capacity of granulocytes and monocytes after polytrauma.Methods: Eight pigs (Sus scrofa) underwent polytrauma consisting of lung contusion, liver laceration, tibial fracture and hemorrhagic shock with fluid resuscitation and fracture fixation with external fixator. Intensive care treatment including mechanical ventilation for 72 h followed. Phagocytic activity and capacity were investigated using an in vitro ex vivo whole blood stimulation phagocytosis assays before trauma, after surgery, 24, 48, and 72 h after trauma. Blood samples were stimulated with Phorbol-12-myristate-13-acetate and incubated with FITC-labeled E. coli, S. aureus or S. cerevisiae for phagocytosis assessment by flow cytometry.Results: Early polytrauma-induced significant increase of granulocytes and monocytes declined to baseline values within 24 h. Percentage of E. coli-phagocytizing granulocytes significantly decreased after polytrauma and during further intensive care treatment, while their capacity significantly increased. Interestingly, both granulocytic phagocytic activity and capacity of S. aureus significantly decreased after trauma, although a recovery was observed after 24 h and yet was followed by another decrease. The percentage of S. cerevisiae-phagocytizing granulocytes significantly increased after 24 h, while their impaired capacity after surgery and 72 h later was detected. Monocytic E. coli-phagocytizing percentage did not change, while their capacity increased after 24–72 h. After a significant decrease in S. aureus-phagocytizing monocytes after surgery, a significant increase after 24 and 48 h was observed without capacity alterations. No significant changes in S. cerevisiae-phagocytizing monocytes occurred, but their capacity dropped 48 and 72 h.Conclusion: Phagocytic activity and capacity of granulocytes and monocytes follow a different pattern and significantly change within 72 h after polytrauma. Both phagocytic activity and capacity show significantly different alterations depending on the pathogen strain, thus potentially indicating at certain and possibly more relevant infection causes after polytrauma.
SARS-CoV-2 Diagnostic Tests: Algorithm and Field Evaluation From the Near Patient Testing to the Automated Diagnostic Platform
Authors: Yin Nicolas , Debuysschere Cyril , Decroly Marc , Bouazza Fatima-Zohra , Collot Vincent , Martin Charlotte , Ponthieux Fanny , Dahma Hafid , Gilbert Marius , Wautier Magali , Duterme Cecile , De Vos Nathalie , Delforge Marie-Luce , Malinverni Stefano , Cotton Frédéric , Bartiaux Magali , Hallin Marie 
Published: April 2021

Introduction:Since the first wave of COVID-19 in Europe, new diagnostic tools using antigen detection and rapid molecular techniques have been developed. Our objective was to elaborate a diagnostic algorithm combining antigen rapid diagnostic tests, automated antigen dosing and rapid molecular tests and to assess its performance under routine conditions.Methods:An analytical performance evaluation of four antigen rapid tests, one automated antigen dosing and one molecular point-of-care test was performed on samples sent to our laboratory for a SARS-CoV-2 reverse transcription PCR. We then established a diagnostic algorithm by approaching median viral loads in target populations and evaluated the limit of detection of each test using the PCR cycle threshold values. A field performance evaluation including a clinical validation and a user-friendliness assessment was then conducted on the antigen rapid tests in point-of-care settings (general practitioners and emergency rooms) for outpatients who were symptomatic for &lt;7 days. Automated antigen dosing was trialed for the screening of asymptomatic inpatients.Results:Our diagnostic algorithm proposed to test recently symptomatic patients using rapid antigen tests, asymptomatic patients using automated tests, and patients requiring immediate admission using molecular point-of-care tests. Accordingly, the conventional reverse transcription PCR was kept as a second line tool. In this setting, antigen rapid tests yielded an overall sensitivity of 83.3% (not significantly different between the four assays) while the use of automated antigen dosing would have spared 93.5% of asymptomatic inpatient screening PCRs.Conclusion:Using tests not considered the “gold standard” for COVID-19 diagnosis on well-defined target populations allowed for the optimization of their intrinsic performances, widening the scale of our testing arsenal while sparing molecular resources for more seriously ill patients.
Gene Therapy in Movement Disorders: A Systematic Review of Ongoing and Completed Clinical Trials
Authors: Merola Aristide , Kobayashi Noelle , Romagnolo Alberto , Wright Brenton A. , Artusi Carlo Alberto , Imbalzano Gabriele , Litvan Irene , Van Laar Amber D. , Bankiewicz Krystof 
Published: April 2021

Introduction:We sought to provide an overview of the published and currently ongoing movement disorders clinical trials employing gene therapy, defined as a technology aiming to modulate the expression of one or more genes to achieve a therapeutic benefit.Methods:We systematically reviewed movement disorders gene therapy clinical trials from PubMed andClinicalTrials.govusing a searching strategy that included Parkinson disease (PD), Huntington disease (HD), amino acid decarboxylase (AADC) deficiency, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dystonia, tremor, ataxia, and other movement disorders. Data extracted included study characteristics, investigational product, route of administration, safety/tolerability, motor endpoints, and secondary outcomes (i.e., neuroimaging, biomarkers).Results:We identified a total of 46 studies focusing on PD (21 published and nine ongoing), HD (2 published and 5 ongoing), AADC deficiency (4 published and 2 ongoing), MSA (2 ongoing), and PSP (1 ongoing). In PD, intraparenchymal infusion of viral vector-mediated gene therapies demonstrated to be safe and showed promising preliminary data in trials aiming at restoring the synthesis of dopamine, enhancing the production of neurotrophic factors, or modifying the functional interaction between different nodes of the basal ganglia. In HD, monthly intrathecal delivery of an antisense oligonucleotide (ASO) targeting the huntingtin protein (HTT) mRNA proved to be safe and tolerable, and demonstrated a dose-dependent reduction of the cerebrospinal fluid levels of mutated HTT, while a small phase-I study testing implantable capsules of cells engineered to synthesize ciliary neurotrophic factor failed to show consistent drug delivery. In AADC deficiency, gene replacement studies demonstrated to be relatively safe in restoring catecholamine and serotonin synthesis, with promising outcomes. Ongoing movement disorders clinical trials are focusing on a variety of gene therapy approaches including alternative viral vector serotypes, novel recombinant genes, novel delivery techniques, and ASOs for the treatment of HD, MSA, and distinct subtypes of PD (LRRK2 mutation or GBA1 mutation carriers).Conclusion:Initial phase-I and -II studies tested the safety and feasibility of gene therapy in PD, HD, and AADC deficiency. The ongoing generation of clinical trials aims to test the efficacy of these approaches and explore additional applications for gene therapy in movement disorders.
Phosphate Brain Energy Metabolism and Cognition in Alzheimer’s Disease: A Spectroscopy Study Using Whole-Brain Volume-Coil 31Phosphorus Magnetic Resonance Spectroscopy at 7Tesla
Authors: Das Namrata , Ren Jimin , Spence Jeffrey , Chapman Sandra Bond 
Published: April 2021

IntroductionMitochondrial dysfunction is a neurometabolic hallmark signaling abnormal brain energy metabolism (BEM) targeted as a potential early marker of Alzheimer’s disease (AD). Advanced imaging technologies, such as 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7T, provide sensitive phosphate-BEM (p-BEM) data with precision. The study’s first goal was to develop a methodology to measure phosphate energy and membrane metabolites simultaneously across the whole-brain using volume-coil 31P MRS at 7T in three groups-cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and AD. The second aim investigated whether p-BEM markers in the four brain regions-frontal, temporal, parietal, and occipital were significantly different across the three groups. The final goal examined correspondence between the p-BEM markers and cognition in the three groups.MethodsForty-one participants (CN = 15, aMCI = 15, AD = 11) were enrolled and completed cognitive assessment and scan. The cognitive domains included executive function (EF), memory, attention, visuospatial skills, and language. The p-BEM markers were measured using energy reserve index (PCr/t-ATP), energy consumption index (intracellular_Pi/t-ATP), metabolic state indicator (intracellular_Pi/PCr), and regulatory co-factors [magnesium (Mg2+) and intracellular pH].ResultsThirteen metabolites were measured simultaneously from the whole brain for all three group with high spectral resolution at UHF. In the aMCI group, a lower p-BEM was observed compared to CN group based on two markers, i.e., energy reserve (p = 0.009) and energy consumption (p = 0.05) indices; whereas in AD a significant increase was found in metabolic stress indicator (p = 0.007) and lower Mg2+ (p = 0.004) in the temporal lobes compared to aMCI using ANOVA between group analytical approach. Finally, using a linear mixed model, a significant positive correlation was found between Mg2+ and cognitive performance of memory (p = 0.013), EF (p = 0.023), and attention (p = 0.0003) in CN but not in aMCI or AD.ConclusionTo our knowledge, this is the first study to show that it is possible to measure p-BEM in vivo with precision at UHF across the three groups. Moreover, the findings suggest that p-BEM may be compromised in aMCI even before an AD diagnosis, which in future studies should explore to examine whether this energy crisis contributes to some of the earliest neuropathophysiologic changes in AD.
Multi-Omics Analysis of Brain Metastasis Outcomes Following Craniotomy
Authors: Su Jing , Song Qianqian , Qasem Shadi , O’Neill Stacey , Lee Jingyun , Furdui Cristina M. , Pasche Boris , Metheny-Barlow Linda , Masters Adrianna H. , Lo Hui-Wen , Xing Fei , Watabe Kounosuke , Miller Lance D. , Tatter Stephen B. , Laxton Adrian W. , Whitlow Christopher T. , Chan Michael D. , Soike Michael H. , Ruiz Jimmy 
Published: April 2021

BackgroundThe incidence of brain metastasis continues to increase as therapeutic strategies have improved for a number of solid tumors. The presence of brain metastasis is associated with worse prognosis but it is unclear if distinctive biomarkers can separate patients at risk for CNS related death.MethodsWe executed a single institution retrospective collection of brain metastasis from patients who were diagnosed with lung, breast, and other primary tumors. The brain metastatic samples were sent for RNA sequencing, proteomic and metabolomic analysis of brain metastasis. The primary outcome was distant brain failure after definitive therapies that included craniotomy resection and radiation to surgical bed. Novel prognostic subtypes were discovered using transcriptomic data and sparse non-negative matrix factorization.ResultsWe discovered two molecular subtypes showing statistically significant differential prognosis irrespective of tumor subtype. The median survival time of the good and the poor prognostic subtypes were 7.89 and 42.27 months, respectively. Further integrated characterization and analysis of these two distinctive prognostic subtypes using transcriptomic, proteomic, and metabolomic molecular profiles of patients identified key pathways and metabolites. The analysis suggested that immune microenvironment landscape as well as proliferation and migration signaling pathways may be responsible to the observed survival difference.ConclusionA multi-omics approach to characterization of brain metastasis provides an opportunity to identify clinically impactful biomarkers and associated prognostic subtypes and generate provocative integrative understanding of disease.
Development of a Prognostic AI-Monitor for Metastatic Urothelial Cancer Patients Receiving Immunotherapy
Authors: Trebeschi Stefano , Bodalal Zuhir , van Dijk Nick , Boellaard Thierry N. , Apfaltrer Paul , Tareco Bucho Teresa M. , Nguyen-Kim Thi Dan Linh , van der Heijden Michiel S. , Aerts Hugo J. W. L. , Beets-Tan Regina G. H. 
Published: April 2021

Background: Immune checkpoint inhibitor efficacy in advanced cancer patients remains difficult to predict. Imaging is the only technique available that can non-invasively provide whole body information of a patient's response to treatment. We hypothesize that quantitative whole-body prognostic information can be extracted by leveraging artificial intelligence (AI) for treatment monitoring, superior and complementary to the current response evaluation methods.Methods: To test this, a cohort of 74 stage-IV urothelial cancer patients (37 in the discovery set, 37 in the independent test, 1087 CTs), who received anti-PD1 or anti-PDL1 were retrospectively collected. We designed an AI system [named prognostic AI-monitor (PAM)] able to identify morphological changes in chest and abdominal CT scans acquired during follow-up, and link them to survival.Results: Our findings showed significant performance of PAM in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.73 (p &lt; 0.001) for abdominal imaging, and 0.67 AUC (p &lt; 0.001) for chest imaging. Subanalysis revealed higher accuracy of abdominal imaging around and in the first 6 months of treatment, reaching an AUC of 0.82 (p &lt; 0.001). Similar accuracy was found by chest imaging, 5–11 months after start of treatment. Univariate comparison with current monitoring methods (laboratory results and radiological assessments) revealed higher or similar prognostic performance. In multivariate analysis, PAM remained significant against all other methods (p &lt; 0.001), suggesting its complementary value in current clinical settings.Conclusions: Our study demonstrates that a comprehensive AI-based method such as PAM, can provide prognostic information in advanced urothelial cancer patients receiving immunotherapy, leveraging morphological changes not only in tumor lesions, but also tumor spread, and side-effects. Further investigations should focus beyond anatomical imaging. Prospective studies are warranted to test and validate our findings.
Neurological and Cognitive Performance After Childhood Encephalitis
Authors: Pöyhönen Heidi , Setänen Sirkku , Isaksson Nea , Nyman Mikko , Nyman Anna , Peltola Ville , Lähdesmäki Tuire 
Published: April 2021

Background: Children with encephalitis have increased risk for long-term neurological sequelae. We investigated minor neurological dysfunction (MND) and cognitive performance as a measurement for long-term outcome of encephalitis in childhood.Materials and Methods: Children with encephalitis (n = 98) treated in Turku University Hospital during the years 1995–2016 were retrospectively identified. We included the patients without severe developmental delay before the encephalitis and without recorded neurological disability caused by encephalitis. MND was assessed using the Touwen examination. Age-appropriate Wechsler Intelligence Scale was used to determine the full-scale intelligence quotient (IQ). Residual symptoms in everyday life were evaluated using a questionnaire.Results: Forty-two subjects participated in the study and returned the questionnaire regarding residual symptoms. The median age was 4.3 years at the time of encephalitis, and 11.3 years at the time of the Touwen examination (n = 41) and the cognitive assessment (n = 38). The Touwen examination indicated MND in 29 of 41 participants (71%; simple MND in 16 and complex MND in 13 patients). The median full-scale IQ was lower in participants with MND compared with participants without MND (98 vs. 110, p = 0.02). Participants with IQ &lt; 85 (n = 5) had lower median age at acute encephalitis compared to participants with IQ ≥ 85 (n = 33) (1.8 vs. 5.3 years, p = 0.03). Problems in daily performance were reported in participant with MND (p = 0.2) and low full-scale IQ (p = 0.008).Conclusions: The prevalence of MND was high and it was related to lower cognitive performance after childhood encephalitis. Younger age at acute encephalitis was a risk factor for lower cognitive performance.
Young People Who Meaningfully Improve Are More Likely to Mutually Agree to End Treatment
Authors: Edbrooke-Childs Julian , Costa da Silva Luís , Čuš Anja , Liverpool Shaun , Pinheiro Mota Catarina , Pietrabissa Giada , Bardsley Thomas , Sales Celia M. D. , Ulberg Randi , Jacob Jenna , Ferreira Nuno 
Published: April 2021

Objective: Symptom improvement is often examined as an indicator of a good outcome of accessing mental health services. However, there is little evidence of whether symptom improvement is associated with other indicators of a good outcome, such as a mutual agreement to end treatment. The aim of this study was to examine whether young people accessing mental health services who meaningfully improved were more likely to mutually agree to end treatment.Methods: Multilevel multinomial regression analysis controlling for age, gender, ethnicity, and referral source was conducted on N = 8,995 episodes of care [Female = 5,469, 61%; meanAge = 13.66 (SD = 2.87) years] using anonymised administrative data from young people's mental health services.Results: Compared to young people with no change in mental health difficulties, those showing positive meaningful changes in mental health difficulties were less likely to have case closure due to non-mutual agreement (Odds Ratio or OR = 0.58, 95% Confidence Interval or CI = 0.50–0.61). Similarly, they were less likely to transfer (OR = 0.61, 95% CI = 0.49–0.74) or end treatment for other reasons (OR = 0.59, 95% CI = 0.50–0.70) than by case closure due to mutual agreement.Conclusion: The findings suggest that young people accessing mental health services whose symptoms meaningfully improve are more likely to mutually agree to end treatment, adding to the evidence that symptom improvement may be appropriate to examine as an indicator of a good outcome of accessing mental health services.
Treatment for Major Depressive Disorder by Repetitive Transcranial Magnetic Stimulation in Different Parameters: A Randomized Double-Blinded Controlled Trial
Authors: Zhang Tingting , Huang Yueqin , Jin Yi , Ma Xiaoyan , Liu Zhaorui 
Published: April 2021

Background: Repetitive transcranial magnetic stimulation (rTMS) has been proven to be safe and effective in treating major depressive disorder (MDD). However, the treatment parameters of rTMS are still divergent and need to be optimized further. The aim of this study was to compare the efficacy of rTMS in treating MDD with different parameters of stimulating frequency and location, and course of treatment.Methods: A total of 221 patients with MDD were recruited in the randomized, double-blind, controlled trial. All eligible patients were randomly assigned into four treatment groups: (1) 10 Hz in left dorsolateral pre-frontal cortex (DLPFC) (n = 55), (2) 5 Hz in left DLPFC (n = 53), (3) 10 Hz in bilateral DLPFC (n = 57), and (4) 5 Hz in bilateral DLPFC (n = 56). The patients received treatment for 6 weeks and an additional 6-week optional treatment. The efficacies were evaluated by Hamilton Depression Rating Scale-24 items (HDRS) and Clinical Global Impressions Scale (CGI). The trial is registered at the Chinese Clinical Trial Registry as ChiCTR-TRC-12002248.Results: The ANOVAs of HDRS scores up to 6 weeks and 12 weeks with repeated measure of time showed a significant effect of duration without statistical difference among four treatment groups and no significance when time was interacted with inter-group as well. The response rates up until the 5th week were significantly different with the previous week.Conclusions: It concludes that there were no statistical differences in the efficacy of rTMS between unilateral left and bilateral DLPFC, and between 5 and 10 Hz for treating MDD.