Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Donepezil on Problem-solving Ability in Individuals With Amnestic Mild Cognitive Impairment: A Pilot Study

Background: Clinical trials involving individuals with mild cognitive impairment (MCI) have reported mixed results for the effects of cholinesterase inhibitors on cognitive outcomes. Our previous work demonstrated that a visuospatial problem-solving task was sensitive to non-memory impairments in individuals with MCI. Objective: To determine whether the same task is also sensitive to the effects of cholinesterase inhibitors in individuals with amnestic MCI (aMCI). Method: We gave 22 individuals with aMCI (clinical dementia rating of 0.5) and Mini-Mental State Examination (MMSE) scores of at least 24 the following measures at baseline and at follow-up 1 year later: Hopkins Verbal Learning Test, Boston Naming Test, Rey Complex Figures Test copying task, anagrams task, and visuospatial problem-solving task. The MMSE was also given at the 1-year follow-up. Twelve of the individuals were drug naïve, having never taken cholinesterase inhibitors before, and donepezil was initiated and titrated to 10 mg daily after baseline in an open-label manner. Ten of the individuals had already been taking donepezil, and there was no change in treatment. We compared the two groups for amount of performance change over 1 year. Results: Individuals for whom donepezil was initiated performed significantly better on the visuospatial problem-solving task after 1 year compared with individuals who had already been taking donepezil. No difference was observed for any of the other variables. Conclusion: The visuospatial problem-solving task appeared to be more sensitive than memory measures to the effects of cholinesterase inhibitors in individuals with aMCI, perhaps due to the high attentional demand of the task.
Effect of the non-ideal axial ratio c/a on anharmonic EXAFS oscillation of h.c.p. crystals.

The temperature and wavenumber dependence of the extended X-ray absorption fine-structure (EXAFS) oscillation of hexagonal close-packed (h.c.p.) crystals have been calculated and analyzed under the effect of the non-ideal axial ratio c/a. The anharmonic EXAFS oscillation is presented in terms of the Debye-Waller factor using the cumulant expansion approach up to the fourth order. An effective calculation model is expanded and developed from the many-body perturbation approach and correlated Debye model using the anharmonic effective potential. This potential, depending on the non-ideal axial ratio c/a, is obtained from the first-shell near-neighbor contribution approach. A suitable analysis procedure is performed by evaluating the influence of EXAFS cumulants on the phase shift and amplitude reduction of the anharmonic EXAFS oscillation. The numerical results for crystalline zinc are found to be in good agreement with those obtained from experiments and other theoretical methods at various temperatures. The obtained results show that the present theoretical model is essential and effective in improving the accuracy for analyzing the experimental data of anharmonic EXAFS signals of h.c. p. crystals with a non-ideal axial ratio c/a.
A case of an atypical teratoid/rhabdoid tumor with distinctive histology in the pineal region in an adult patient

A 31‐year‐old man suffered from headaches and presented at a hospital after the symptom worsened. Obstructive hydrocephalus and a pineal tumor were identified, and he was transferred to our hospital for further investigation and treatment. Cranial computed tomography revealed a hypodense mass lesion on the right of the pineal region, and calcifications and enlargement of the lateral and third cerebral ventricles were also evident. Blood tests were negative for all tumor markers. Laparoscopic biopsy and third‐ventricle fenestration were performed that day as an emergency surgery to treat the obstructive hydrocephalus. Postoperative cranial magnetic resonance imaging revealed a solid tumor that was hypointense on T1‐weighted imaging, hyperintense on T2‐weighted imaging, and heterogeneously enhanced by Gd. Subsequently, the tumor increased in size, and craniotomy and tumorectomy were performed. Histologically, the tumor proliferated as round or short spindle‐shaped cells in a myxoid matrix, forming arrays that surrounded the blood vessels. As a few cells with eosinophilic cytoplasm were also present and immunostaining for INI‐1 was negative, the patient was diagnosed with atypical teratoid/rhabdoid tumor (AT/RT). AT/RT of the pineal region in adults is rare, and herein, we report the morphological characteristics of this case and reviewed the relevant literature.
Real-time Optoacoustic Monitoring of Ablation Treatments in Medicine

Ablation procedures have been applied in various medical fields for the purpose of removing or destroying diseased tissues. However, the lack of sensory feedback during ablation procedures still yields a non-negligible risk of ineffective treatments or collateral damage to healthy surrounding tissues. The aim of this work was therefore to investigate how Optoacoustics, a promising and versatile modality in Biomedical Imaging and Sensing, can be utilized to monitor biophysical processes occurring during ablation, in order to provide direct and precise feedback on the outcome of the ablation procedure.
Prospective assessment of catheter-associated bacteriuria clinical presentation, epidemiology, and colonization dynamics in nursing home residents

BACKGROUND Catheterization facilitates continuous bacteriuria, for which the clinical significance remains unclear. This study aimed to determine the clinical presentation, epidemiology, and dynamics of bacteriuria in a cohort of long-term catheterized nursing home residents. METHODS Prospective urine culture, urinalysis, chart review, and assessment of signs and symptoms of infection were performed weekly for 19 study participants over 7 months. All bacteria ≥ 1 × 103 cfu/mL were cultured, isolated, identified, and tested for susceptibility to select antimicrobials. RESULTS In total, 226 of the 234 urine samples were polymicrobial (97%), with an average of 4.7 isolates per weekly specimen. A total of 228 urine samples (97%) exhibited ≥ 1 × 106 CFU/mL, 220 (94%) exhibited abnormal urinalysis, 126 (54%) were associated with at least 1 possible sign or symptom of infection, and 82 (35%) would potentially meet a standardized definition of catheter-associated urinary tract infection (CAUTI), but only 3 had a caregiver diagnosis of CAUTI. Bacterial isolates (286; 30%) were resistant to a tested antimicrobial agent, and bacteriuria composition was remarkably stable despite a combined total of 54 catheter changes and 23 weeks of antimicrobial use. CONCLUSION Bacteriuria composition was largely polymicrobial, including persistent colonization by organisms previously considered to be urine culture contaminants. Neither antimicrobial use nor catheter changes sterilized the urine, at most resulting in transient reductions in bacterial burden followed by new acquisition of resistant isolates. Thus, this patient population exhibits a high prevalence of bacteriuria coupled with potential indicators of infection, necessitating further exploration to identify sensitive markers of true infection. FUNDING This work was supported by the NIH (R00 DK105205, R01 DK123158, UL1 TR001412).
Excessive Laughter-like Vocalizations, Microcephaly, and Translational Outcomes in the Ube3a Deletion Rat Model of Angelman Syndrome

Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder characterized by intellectual disabilities, motor and balance deficits, impaired communication, and a happy, excitable demeanor with frequent laughter. We sought to elucidate a preclinical outcome measure in male and female rats that addressed communication abnormalities of AS and other neurodevelopmental disorders in which communication is atypical and/or lack of speech is a core feature. We discovered, and herein report for the first time, excessive laughter-like 50 kHz ultrasonic emissions in the Ube3amat–/pat+ rat model of AS, which suggests an excitable, playful demeanor and elevated positive affect, similar to the demeanor of individuals with AS. Also in line with the AS phenotype, Ube3amat–/pat+ rats demonstrated aberrant social interactions with a novel partner, distinctive gait abnormalities, impaired cognition, an underlying LTP deficit, and profound reductions in brain volume. These unique, robust phenotypes provide advantages compared with currently available mouse models and will be highly valuable as outcome measures in the evaluation of therapies for AS. SIGNIFICANCE STATEMENT Angelman syndrome (AS) is a severe neurogenetic disorder for which there is no cure, despite decades of research using mouse models. This study used a recently developed rat model of AS to delineate disease-relevant outcome measures to facilitate therapeutic development. We found the rat to be a strong model of AS, offering several advantages over mouse models by exhibiting numerous AS-relevant phenotypes, including overabundant laughter-like vocalizations, reduced hippocampal LTP, and volumetric anomalies across the brain. These findings are unconfounded by detrimental motor abilities and background strain, issues plaguing mouse models. This rat model represents an important advancement in the field of AS, and the outcome metrics reported herein will be central to the therapeutic pipeline.
Six Month Efficacy and Toxicity Profile of BNT162b2 Vaccine in Cancer Patients with Solid Tumors.

We had previously reported short-term efficacy, immunogenicity and safety of BNT162b2 vaccine among cancer patients with solid tumors. We aimed to evaluate these outcomes at 6-months post-vaccination. Study cohort comprised of patients who were on treatment during vaccination and throughout 6-months post-vaccination. Serological tests were performed after second vaccination and 6-months afterwards. An age-matched cohort of healthcare workers served as controls. Documentation of COVID-19 infection, blood tests and imaging studies during study period was reviewed. Participants included 154 patients and 135 controls. Six-months post-vaccination, 122(79%) of patients were seropositive compared with 114(84%) of controls (p-0.32). Serology titer dramatically decreased similarly in both cohorts. No COVID-19 cases were documented in controls and one case occurred in patient cohort. All previously reported adverse effects resolved. Taken together, the pattern of immunogenicity, efficacy and safety of BNT162b2 in cancer patients with solid tumors at 6 months post-vaccination resemble that of the general population.
Long non-coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation-induced pyroptosis via microRNA-448/gasdermin E in colorectal cancer cells

Pyroptosis is mediated by gasdermins and serves a critical role in ionizing radiation (IR)-induced damage in normal tissues, but its role in cancer radiotherapy and underlying mechanisms remains unclear. Long non-coding (lnc) RNAs serve important roles in regulating the radiosensitivity of cancer cells. The present study aimed to investigate the mechanistic involvement of lncRNAs in IR-induced pyroptosis in human colorectal cancer HCT116 cells. LncRNA, microRNA (miR)-448 and gasdermin E (GSDME) levels were evaluated using reverse transcription-quantitative polymerase chain reaction. Protein expression and activation of gasdermins were measured using western blotting. The binding association between miR-448 and GSDME was assessed using the dual-luciferase reporter assay. Pyroptosis was examined using phase-contrast microscopy, flow cytometry, Cell Counting Kit-8 assay and lactate dehydrogenase release assay. IR dose-dependently induced GSDME-mediated pyroptosis in HCT116 cells. GSDME was identified as a downstream target of miR-448. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was upregulated in response to IR and enhanced GSDME expression by negatively regulating miR-448 expression. Notably, NEAT1 knockdown suppressed IR-induced pyroptosis, full-length GSDME expression and GSDME cleavage compared with that in irradiated cells. In addition, NEAT1 knockdown rescued the IR-induced decrease in cell viability in HCT116 cells. The findings of the present study indicated that lncRNA NEAT1 modulates IR-induced pyroptosis and viability in HCT116 cells via miR-448 by regulating the expression, but not activation of GSDME. The present study provides crucial mechanistic insight into the potential role of lncRNA NEAT1 in IR-induced pyroptosis.
Incidence of Proliferative Diabetic Retinopathy and Other Neovascular Sequelae at 5 Years Following Diagnosis of Type 2 Diabetes

OBJECTIVE To determine the incidence and risk factors for developing proliferative diabetic retinopathy (PDR), tractional retinal detachment (TRD), and neovascular glaucoma (NVG) at 5 years after the initial diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS Insured patients aged ≥18 years with newly diagnosed type 2 diabetes and 5 years of continuous enrollment were identified from a nationwide commercial claims database containing data from 2007 to 2015. The incidences of PDR, TRD, and NVG were computed at 5 years following the index diagnosis of type 2 diabetes. Associations between these outcomes and demographic, socioeconomic, and medical factors were tested with multivariable logistic regression. RESULTS At 5 years following the initial diagnosis of type 2 diabetes, 1.74% (1,249 of 71,817) of patients had developed PDR, 0.25% of patients had developed TRD, and 0.14% of patients had developed NVG. Insulin use (odds ratio [OR] 3.59, 95% CI 3.16–4.08), maximum HbA1c >9% or >75 mmol/mol (OR 2.10, 95% CI 1.54–2.69), renal disease (OR 2.68, 95% CI 2.09–3.42), peripheral circulatory disorders (OR 1.88, 95% CI 1.25–2.83), neurological disease (OR 1.62, 95% CI 1.24–2.11), and older age (age 65–74 years) at diagnosis (OR 1.62, 95% CI 1.28–2.03) were identified as risk factors for development of PDR at 5 years. Young age (age 18–23 years) at diagnosis (OR 0.46, 95% CI 0.29–0.74), Medicare insurance (OR 0.60, 95% CI 0.70–0.76), morbid obesity (OR 0.72, 95% CI 0.59–0.87), and smoking (OR 0.84, 95% CI 0.70–1.00) were identified as protective factors. CONCLUSIONS A subset of patients with type 2 diabetes develop PDR and other neovascular sequelae within the first 5 years following the diagnosis with type 2 diabetes. These patients may benefit from increased efforts for screening and early intervention.
Should we individualize training based on force‐velocity profiling to improve physical performance in athletes?

The present study aimed to examine the effectiveness of an individualized training program based on force‐velocity (FV) profiling on jumping, sprinting, strength, and power in athletes. Forty national level team sport athletes (20 ± 4years, 83 ± 13 kg) from ice‐hockey, handball, and soccer completed a 10‐week training intervention. A theoretical optimal squat jump (SJ)‐FV‐profile was calculated from SJ with five different loads (0, 20, 40, 60, and 80 kg). Based on their initial FV‐profile, athletes were randomized to train toward, away, or irrespective (balanced training) of their initial theoretical optimal FV‐profile. The training content was matched between groups in terms of set x repetitions but varied in relative loading to target the different aspects of the FV‐profile. The athletes performed 10 and 30 m sprints, SJ and countermovement jump (CMJ), 1 repetition maximum (1RM) squat, and a leg‐press power test before and after the intervention. There were no significant group differences for any of the performance measures. Trivial to small changes in 1RM squat (2.9%, 4.6%, and 6.5%), 10 m sprint time (1.0%, −0.9%, and −1.7%), 30 m sprint time (0.9%, −0.6%, and −0.4%), CMJ height (4.3%, 3.1%, and 5.7%), SJ height (4.8%, 3.7%, and 5.7%), and leg‐press power (6.7%, 4.2%, and 2.9%) were observed in the groups training toward, away, or irrespective of their initial theoretical optimal FV‐profile, respectively. Changes toward the optimal SJ‐FV‐profile were negatively correlated with changes in SJ height (r = −0.49, p < 0.001). Changes in SJ‐power were positively related to changes in SJ‐height (r = 0.88, p < 0.001) and CMJ‐height (r = 0.32, p = 0.044), but unrelated to changes in 10 m (r = −0.02, p = 0.921) and 30 m sprint time (r = −0.01, p = 0.974). The results from this study do not support the efficacy of individualized training based on SJ‐FV profiling.
Structural basis of P[II] rotavirus evolution and host ranges under selection of histo-blood group antigens

Significance Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. Existing RV vaccines are successful in many developed countries, but their efficacy remains poor in developing countries, which could be due to lack of cross protection between RV genotypes more common in developed countries and other P-type RVs less common in developed countries but common in developing countries. In this study, crystal structures of major P[II] genogroup VP8* receptor domains in complex with Lewis epitope–containing histo-blood group antigen (HBGA) glycans were determined, revealing the structural basis for RV HBGA receptor specificities that determine RV host ranges. The data should enable rationale design of next-generation RV vaccines. Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. RVs have diverse host ranges in different human and animal populations determined by host histo-blood group antigen (HBGA) receptor polymorphism, but details governing diversity, host ranges, and species barriers remain elusive. In this study, crystal structures of complexes of the major P[II] genogroup P[4] and P[8] genotype RV VP8* receptor–binding domains together with Lewis epitope–containing LNDFH I glycans in combination with VP8* receptor-glycan ligand affinity measurements based on NMR titration experiments revealed the structural basis for RV genotype-specific switching between ββ and βα HBGA receptor–binding sites that determine RV host ranges. The data support the hypothesis that P[II] RV evolution progressed from animals to humans under the selection of type 1 HBGAs guided by stepwise host synthesis of type 1 ABH and Lewis HBGAs. The results help explain disease burden, species barriers, epidemiology, and limited efficacy of current RV vaccines in developing countries. The structural data has the potential to impact the design of future vaccine strategies against RV gastroenteritis.
Vaccination coverage among school children in Western Greece from 2016 to 2019

ABSTRACT Vaccine hesitancy has increased, which has an effect on vaccine uptake. The aim of our study was to investigate childhood vaccination coverage in Western Greece and identify factors affecting it. We also aimed to assess trends in childhood vaccination coverage nationwide. A cross-sectional study was conducted (2016–2019) in all the primary schools in Patras, the third largest city in the country. Data collection was undertaken using child vaccination booklets and questionnaires on socio-demographics. Multiple regression analyses were performed to evaluate relevant associations. We also performed a systematic review of published data on childhood vaccination coverage in Greece during the last two decades. Data for 1657 children was collected and 371 questionnaires were returned. High vaccination coverage (>90%) was observed for the majority of the vaccines. For the pneumococcal conjugate vaccine (PCV), coverage with four doses, as recommended at the time of study, was suboptimal (39.2%). For human papillomavirus vaccines and the meningococcal serogroup B vaccine, full vaccination coverage was 2.6% and 6.5%, respectively. No association with socio-demographics was found for vaccines with high coverage. For PCV the number of doses given was related to Greek nationality (β = 0.185, p < .001) and parental employment status (β = −0.115, p = .043). Compared to previous studies (16 eligible), there was a trend toward higher coverage. Public health interventions should focus on increasing vaccine uptake of specific vaccines among populations with particular characteristics. A national network recording vaccine coverage is urgently required in the country to monitor vaccine uptake and assess trends over time.
Bioresilience to Mercury Chloride of the Brine Shrimp Artemia Salina after Treatment with Homeopathic Mercurius Corrosivus

Abstract Introduction Finding solutions to mitigate the impact of pollution on living systems is a matter of great interest. Homeopathic preparations of toxic substances have been described in the literature as attenuation factors for intoxication. Herein, an experimental study using Artemia salina and mercury chloride was developed as a model to identify aspects related to bioresilience. Aims The aim of the study was to describe the effects of homeopathic Mercurius corrosivus (MC) on Artemia salina cysts hatching and on mercury bioavailability. Methods Artemia salina cysts were exposed to 5.0 µg/mL of mercury chloride during the hatching phase. MC potencies (6cH, 30cH, and 200cH) were prepared in sterile purified water and poured into artificial sea water. Different controls were used (non-challenged cysts and challenged cysts treated with water, succussed water, and Ethilicum 1cH). Four series of nine experiments were performed to evaluate the percentage of cyst hatching. Soluble total mercury (THg) levels and precipitated mercury content were also evaluated. Solvatochromic dyes were used to check for eventual physicochemical markers of MC biological activity. Results Significant delay (p < 0.0001) in cyst hatching was observed only after treatment with MC 30cH, compared with controls. This result was associated with an increase of THg concentration in water (p = 0.0018) and of chlorine/oxygen ratio (p < 0.0001) in suspended micraggregates, suggesting changes in mercury bioavailability. A specific interaction of MC 30cH with the solvatochromic dye ET33 (p = 0.0017) was found. Conclusion Changes in hatching rate and possible changes in Hg bioavailability are postulated as protective effects of MC 30cH on Artemia salina, by improving its natural bioresilience processes.