bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer’s disease
Authors: Ng Kok Pin , Pascoal Tharick A. , Mathotaarachchi Sulantha , Chan Yiong Huak , Jiang Lai , Therriault Joseph , Benedet Andrea L. , Shin Monica , Kandiah Nagaendran , Greenwood Celia M.T. , Rosa-Neto Pedro , Gauthier Serge 
Published: November 2020

Abstract
Background: Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic mutation. Hence, the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing pathologies. In this longitudinal study, we aim to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers.Methods: We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer’s Network according to their mutation carrier status. Regression mixed effect models with family-level random effects evaluated the interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q), age and estimated years of onset (EYO) as a function of metabolism measured by [18F]flurodeoxyglucose ([18F]FDG) positron emission tomography in DIAD mutation and non-mutation carriers. An exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q sub-components. Regression mixed effect models then evaluated the interactions of specific neuropsychiatric subsyndromes with EYO on metabolism.Results: 119 mutation and 102 non-mutation carriers were studied. The interaction of higher NPI-Q and shorter EYO was associated with more rapid global and regional [18F]FDG uptake decline in the posterior cingulate and ventromedial prefrontal cortices, bilateral parietal lobes and right insula in DIAD mutation carriers. The neuropsychiatric subsyndrome of agitation, disinhibition, irritability and depression interacted with EYO to drive [18F]FDG uptake decline in the DIAD mutation carriers. The interaction of NPI and EYO was not associated with [18F]FDG uptake in DIAD non-mutation carriers.Conclusions: NPS in cognitively intact DIAD mutation carriers may be clinical indicators of subsequent metabolic decline in brain networks vulnerable to AD, which support the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD. Further studies using different methodological approaches to identify NPS in preclinical AD are needed to validate our findings.
The regional diversity of gut microbiome along the GI tract of male C57BL/6 mice
Authors: Lkhagv Enkhchimeg , Chung Hea-Jong , Hong Jinny , Tang Wai Hong Wilson , Lee Sang-Il , Hong Seong-Tshool , Lee Seungkoo 
Published: November 2020

Abstract
Background: The proliferation and survival of microbial organisms including intestinal microbes are determined by their surrounding environments. Contrary to popular myth, the nutritional and chemical compositions, water contents, O2 contents, temperatures, and pH in the gastrointestinal (GI) tract of a human are very different in a location-specific manner, implying heterogeneity of the microbial composition in a location-specific manner.Results: We first investigated the environmental conditions at 6 different locations along the GI tract and feces of ten weeks’ old male SPF C57BL/6 mice. As previously known, the pH and water contents of the GI contents at the different locations of the GI tract were very different from each other in a location-specific manner, and none of which were not even similar to those of feces. After confirming the heterogeneous nature of the GI contents in specific locations and feces, we thoroughly analyzed the composition of the microbiome of the GI contents and feces. 16S rDNA-based metagenome sequencing on the GI contents and feces showed the presence of 13 different phyla. The abundance of Firmicutes gradually decreased from the stomach to feces while the abundance of Bacteroidetes gradually increased. The taxonomic α-diversities measured by ACE (Abundance-based Coverage Estimator) richness, Shannon diversity, and Fisher’s alpha all indicated that the diversities of gut microbiome at colon and cecum were much higher than that of feces. The diversities of microbiome compositions were lowest in jejunum and ileum while highest in cecum and colon. Interestingly, the diversities of the fecal microbiome were lower than those of the cecum and colon. Beta diversity analyses by NMDS plots, PCA, and unsupervised hierarchical clustering all showed that the microbiome compositions were very diverse in a location-specific manner. Direct comparison of the fecal microbiome with the microbiome of the whole GI tracts by α-and β-diversities showed that the fecal microbiome did not represent the microbiome of the whole GI tractConclusion: The fecal microbiome is different from the whole microbiome of the GI tract, contrary to a baseline assumption of contemporary microbiome research work.
Stability and clinical outcomes of a new one piece toric intraocular lens with anchor-wing haptics
Authors: Sugita Iichiro , Ogawa Tomoichiro , Ichikawa Kazuo , Okita Takahide , Negishi Kazuno , Nakano Tadashi , Tsuneoka Hiroshi 
Published: November 2020

Abstract
Background: To evaluate the safety and efficacy of a new toric intraocular lens (IOL) with anchor-wing haptics.Methods: The new toric IOL with anchor-wing haptics (NS60YT, NIDEK Co., Ltd.) was implanted in eligible patients with age-related cataracts with preoperative corneal astigmatism of 1.0 D or greater at a university hospital and two private hospitals in Japan. The following IOL cylinder powers were evaluated: 1.50 D (NS60YT3), 2.25 D (NS60YT4), 3.00 D (NS60YT5) and 4.50 D (NS60YT7). All patients were assessed out to 12 months postoperatively. The primary endpoint was uncorrected visual acuity (UCVA) with spherical addition at 6 months postoperatively, and the primary analysis calculated the proportion of eyes with UCVA with spherical addition of 0.1 logMAR or better. The magnitude of rotation was compared to the intended axis of IOL implantation at each postoperative examination. Adverse events were evaluated for the safety analysis. Results: This study enrolled 64 eyes of 53 patients. At 6 months postoperatively, for all IOL powers, UCVA with spherical addition of 0.1 logMAR or better was achieved in 90% [95% confidence interval (CI): 80-96] of eyes. The mean IOL rotation was 5.3±4.3° at 12 months postoperatively. The mean magnitude of rotation ranged from 1.9° to 2.5° between each postoperative examination from 1 day to 12 months. There were no vision-threatening intraoperative or postoperative complications for the duration of the study.Conclusions: The NS60YT IOL remained stable after implantation and was efficacious for treating 1.00 D or greater astigmatism in patients with senile cataracts.Trial registration: This study was registered at ClinicalTrials.gov (NCT03242486) on August 8, 2017 - Retrospectively registered. (https://clinicaltrials.gov/ct2/show/NCT03242486)
Nomogram for Prediction of fatal outcome in Patients with Severe COVID-19: A Multicenter Study
Authors: Bozzini Giorgio , Maltagliati Matteo , Besana Umberto , Berti Lorenzo , Calori Alberto , Sighinolfi Maria Chiara , Micali Salvatore , Roche Jean Baptiste , Gozen Ali , Mueller Alexander , Pushkar Dimitry , Liatsikos Evangelos , Boldini Marco , Buizza Carlo , Rocco Bernardo 
Published: November 2020

Abstract
Background & Aims: To develop an effective model of predicting fatalOutcome in the severe coronavirus disease 2019 (COVID-19) patients.Methods: Between February 20, 2020 and April 4, 2020, consecutive COVID-19 patients from three designated hospitals were enrolled in this study. Independent high- risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients.Results: There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years (HR 1.184, 95% CI 1.061-1.321), Panting(breathing rate ≥ 30/min) (HR 3.300, 95% CI 2.509-6.286), lymphocyte count < 1.0 × 109/L (HR 2.283, 95% CI 1.779-3.267), and IL-6 >10pg/mL (HR 3.029, 95% CI 1.567-7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC 0.900, [95% CI 0.841-0.960], sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC 0.811, [95% CI 0.763-0.961], sensitivity 77.3%, specificity 73.5); in validation cohort 2 (AUC 0.862, [95% CI 0.698-0.924], sensitivity 92.9%, specificity 64.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. The prognosis of severe COVID-19 patients with high levels of interleukin-6 (IL-6) receiving tocilizumab was better than that of those patients without tocilizumab both in the training and validation cohorts, but without difference (p = 0.105 for training cohort, p = 0.133 for validation cohort 1, and p = 0.210 for validation cohort 2).Conclusions: This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients. Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.
Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi&nbsp;
Authors: Silva Marta G. , Bastos Reginaldo G. , Doggett J. Stone , Riscoe Michael K. , Pou Sovitj , Winter Rolf , Dodean Rozalia A. , Nilsen Aaron , Suarez Carlos E. 
Published: November 2020

Abstract
Background: The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. Endochin-like quinolones (ELQ)-300 and ELQ-316 proved safe and efficacious against related apicomplexans, such as Plasmodium spp., and ELQ-316 was also effective against B. microti, without showing toxicity in mammals.Methods: Inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. Percentage of parasitized erythrocytes was measured by flow cytometry. Effect of the ELQ drugs on the viability of horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by monitoring cell metabolic activity using a colorimetric assay.Results: We calculated IC50 ranging from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 at 72 h among all cultured parasites tested. None of the parasites tested were able to replicate in cultures in the presence of the ELQ-300 and ELQ-316 at IC100, which range from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 h. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing. Conclusions: ELQ-300 and ELQ-316 showed significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.
Associations of poor oral health with frailty and physical functioning in the oldest old: results from two studies in England and Japan
Authors: Albani Viviana , Nishio Kennsuke , Ito Tomoka , Kotronia Eftychia , Moynihan Paula , Robinson Louise , Hanratty Barbara , Kingston Andrew , Abe Yukiko , Takayama Michiyo , Iinuma Toshimitsu , Arai Yasumichi , Ramsay Sheena E 
Published: November 2020

Abstract
Background: Very few studies have examined the relationship of oral health with physical functioning and frailty in the oldest old (>85 years). We examined the association of poor oral health with markers of disability, physical function and frailty in studies of oldest old in England and Japan.Methods: The Newcastle 85+ Study in England (n=853) and the Tokyo Oldest Old Survey on Total Health (TOOTH; n=542) comprise random samples of people aged >85 years. Oral health markers included tooth loss, dryness of mouth, difficulty swallowing and self-reported difficulty eating due to dental problems. Physical functioning was based on grip strength and gait speed; disability was assessed as mobility limitations. Frailty was ascertained using the Fried frailty phenotype. Cross-sectional analyses were undertaken using logistic regression.Results: In the Newcastle 85+ Study, dry mouth symptoms, difficulty swallowing, difficulty eating, and tooth loss were associated with increased risks of mobility limitations after adjustment for gender, socioeconomic position, behavioural factors and co-morbidities [odds ratios (95%CIs) were 1.76 (1.26-2.46); 2.52 (1.56-4.08); 2.89 (1.52-5.50); 2.59 (1.44-4.65) respectively]. Similar results were observed for slow gait speed. Difficulty eating was associated with weak grip strength and frailty on full adjustment. In the TOOTH Study, difficulty eating was associated with increased risks of frailty, mobility limitations and slow gait speed; and complete tooth loss was associated with increased risk of frailty.Conclusion: Different markers of poor oral health are independently associated with worse physical functioning and frailty in the oldest old age groups. Research to understand the underlying pathways is needed.
Incidence of thromboembolism in patients with COVID-19: a systematic review and meta-analysis
Authors: Boonyawat Kochawan , Chantrathammachart Pichika , Numthavej Pawin , Nanthatanti Nithita , Phusanti Sithakom , Phuphuakrat Angsana , Niparuck Pimjai , Angchaisuksiri Pantep 
Published: November 2020

Abstract
Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the incidence of thromboembolism has been increasingly reported. The aim of this systematic review was to explore the incidence of venous and arterial thromboembolism among COVID-19 patients requiring hospitalization.Methods: Medline, Embase, Scopus, and grey literature were searched until May 2020. Observational studies reported on the incidence of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) or arterial thromboembolism (ATE) were included. The pool incidences and their 95% confidence intervals (CI) were calculated using the random-effects model.Results: A total of 36 studies were included. In the intensive care unit (ICU) setting, the pooled incidence of VTE was 28% (95% CI, 22-34%). Subgroups based on compression ultrasound (CUS) screening revealed a higher incidence of DVT in the CUS screening group than in the no CUS screening group (32% [95% CI, 18-45%] vs. 6% [95% CI, 4-9%]). The pooled incidence of ATE in ICU was 3% (95% CI, 2-5%). In the non-ICU setting, the pooled incidence of VTE was 10% (95% CI, 6-14%,).Conclusions:The incidence of VTE in COVID-19 patients was higher in the ICU setting than in the non-ICU setting, and also significantly higher in studies that incorporated the CUS screening protocol. The incidence of ATE in the ICU setting was low. VTE prophylactic measures should be given to all hospitalized patients diagnosed with COVID-19.
Serum D-dimer level as a biomarker for identifying patients with isolated injury to prevent unnecessary whole-body computed tomography in blunt trauma care
Authors: Nakama Rakuhei , Yamamoto Ryo , Izawa Yoshimitsu , Tanimura Keiichi , Mato Takashi 
Published: November 2020

Abstract
Background Unnecessary whole-body computed tomography (CT) may lead to excess radiation exposure. Serum D-dimer levels have been reported to correlate with injury severity. We examined the predictive value of serum D-dimer level for identifying patients with isolated injury that can be diagnosed with selected-region CT rather than whole-body CT.Methods This single-center retrospective cohort study included patients with blunt trauma (2014–2017). We included patients whose serum D-dimer levels were measured before they underwent whole-body CT. “Isolated” injury was defined as injury with Abbreviated Injury Scale (AIS) score ≤ 5 to any of five regions of interest or with AIS score ≤ 1 to other regions, as revealed by a CT scan. A receiver operating characteristic curve (ROC) was drawn for D-dimer levels corresponding to isolated injury; the area under the ROC (AUROC) was evaluated. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for several candidate cut-off values for serum D-dimer levels. Results Isolated injury was detected in 212 patients. AUROC was 0.861 (95% confidence interval [CI]: 0.815–0.907) for isolated injury prediction. Serum D-dimer level ≤ 2.5 μg/mL was an optimal cutoff value for predicting isolated injury with high specificity (100.0 %) and positive predictive value (100.0 %). Approximately 30% of patients had serum D-dimer levels below this cutoff value.Conclusion D-dimer level ≤ 2.5 μg/mL had high specificity and high positive predictive value in cases of isolated injury, which could be diagnosed with selected-region CT, reducing exposure to radiation associated with whole-body CT.
Head phantoms for bioelectromagnetic applications: a material study
Authors: Hunold Alexander , Machts René , Haueisen Jens 
Published: November 2020

Abstract
Background Assessments of source reconstruction procedures in electroencephalography and computations of transcranial electrical stimulation profiles require verification and validation with the help of ground truth configurations as implemented by physical head phantoms. For these phantoms, synthetic materials are needed, which are mechanically and electrochemically stable and possess conductivity values similar to the modeled human head tissues. Three-compartment head models comprise a scalp layer with a conductivity range of 0.137 S/m to 2.1 S/m, a skull layer with conductivity values between 0.066 S/m and 0.00275 S/m, and an intracranial volume with an often-used average conductivity value of 0.33 S/m. To establish a realistically shaped physical head phantom with a well-defined volume conduction configuration, we here characterize the electrical conductivity of synthetic materials for modeling head compartments. We analyzed agarose hydrogel, gypsum, and sodium chloride (NaCl) solution as surrogate materials for scalp, skull, and intracranial volume. We measured the impedance of all materials when immersed in NaCl solution using a four-electrode setup. The measured impedance values were used to calculate the electrical conductivity values of each material. Further, the conductivities in the longitudinal and transverse directions of reed sticks immersed in NaCl solution were measured to test their suitability for mimicking the anisotropic conductivity of white matter tracts.Results We obtained conductivities of 0.314 S/m, 0.30 S/m, 0.311 S/m (2 %, 3 %, 4 % agarose), 0.0425 S/m and 0.0017 S/m (gypsum with and without NaCl in the compound), and 0.332 S/m (0.17 % NaCl solution). These values are within the range of the conductivity values used for EEG and TES modeling. The reed sticks showed anisotropic conductivity with a ratio of 1:2.8. Conclusion We conclude that agarose, gypsum, and NaCl solution can serve as stable representations of the three main conductivity compartments of the head, i.e. scalp, skull, and intracranial volume. An anisotropic conductivity structure such as a fiber track in white matter can be modeled using tailored reed sticks inside a volume conductor.
Evidence of Neuroplasticity With Robotic Hand Exoskeleton Study for Post-Stroke Rehabilitation: A Randomized Controlled Trial
Authors: Singh Neha , Saini Megha , Kumar Nand , Srivast M.V. Padma , Mehndiratta Amit 
Published: November 2020

Abstract
Background: A novel electromechanical robotic-exoskeleton was designed in-house for rehabilitation of wrist joint and Metacarpophalangeal (MCP) joint. Objective: The objective was to compare the rehabilitation effectiveness (clinical-scales and neurophysiological-measures) of robotic-therapy training-sessions with dose-matched control in patients with stroke. Methods: A pilot prospective parallel single-blinded randomized controlled study at clinical-settings was designed with patients with stroke within 2 years of chronicity. Patients were randomly assigned to receive an intervention of 20 sessions of 45-minutes each, five days a week for four-weeks, in Robotic-therapy Group (RG) (n=12) and conventional upper-limb rehabilitation in Control-Group (CG) (n=11). We hypothesized to evaluate the exoskeleton based therapy for the effects on functionality of upper-limb and cortical-excitability in patients with stroke as compared to conventional-rehabilitation. Clinical-scales– Modified Ashworth Scale, Active Range of Motion, Barthel-Index, Brunstrom-stage and Fugl-Meyer scale (Shoulder/Elbow and Wrist/Hand component), and neurophysiological-measures of cortical-excitability (using Transcranial Magnetic Stimulation) –Motor Evoked Potential and Resting Motor-threshold, were acquired pre and post-therapy. No side effects were noticed in any of the patients. Results: RG and CG showed significant (p<0.05) improvement in all clinical motor-outcomes except Modified Ashworth Scale in CG. RG showed significantly (p<0.05) higher improvement over CG in Modified Ashworth Scale, Active Range of Motion and Fugl-Meyer (FM) scale and FM Wrist-/Hand component). Increase in cortical-excitability in ipsilesional-hemisphere was found to be statistically significant (p<0.05) in RG over CG, as indexed by decrease in Resting Motor-Threshold and increase in amplitude of Motor Evoked Potential. No significant changes were shown by the contralesional-hemisphere. Interhemispheric RMT-asymmetry evidenced significant (p<0.05) changes in RG over CG indicating increased cortical-excitability in ipsilesional-hemisphere along with interhemispheric changes. Conclusion: Neurophysiological-changes in RG could most likely be a consequence of plastic-reorganization and use-dependent plasticity. Robotic-exoskeleton training could significantly improve motor-outcomes and cortical-excitability in patients with stroke.