Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates

Background: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. Methods: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. Results: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. Conclusions: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain.
3,3′-Diindolylmethane Enhances the Efficacy of Butyrate in Colon Cancer Prevention through Down-Regulation of Survivin

Butyrate is an inhibitor of histone deacetylase (HDAC) and has been extensively evaluated as a chemoprevention agent for colon cancer. We recently showed that mutations in the adenomatous polyposis coli (APC) gene confer resistance to HDAC inhibitor–induced apoptosis in colon cancers. Here, we show that APC mutation rendered colon cancer cells resistant to butyrate-induced apoptosis due to the failure of butyrate to down-regulate survivin in these cells. Another cancer-preventive agent, 3,3′-diindolylmethane (DIM), was identified to be able to down-regulate survivin in colon cancers expressing mutant APC. DIM inhibited survivin mRNA expression and promoted survivin protein degradation through inhibition of p34cdc2-cyclin B1–mediated survivin Thr34 phosphorylation. Pretreatment with DIM enhanced butyrate-induced apoptosis in colon cancer cells expressing mutant APC. DIM/butyrate combination treatment induced the expression of proapoptotic Bax and Bak proteins, triggered Bax dimerization/activation, and caused release of cytochrome c and Smac proteins from mitochondria. Whereas overexpression of survivin blocked DIM/butyrate–induced apoptosis, knocking down of survivin by small interfering RNA increased butyrate-induced apoptosis in colon cancer cells. We further showed that DIM was able to down-regulate survivin and enhance the effects of butyrate in apoptosis induction and prevention of familial adenomatous polyposis in APCmin/+ mice. Thus, the combination of DIM and butyrate is potentially an effective strategy for the prevention of colon cancer.
Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment.

BACKGROUND Donepezil is an acetylcholinesterase inhibitor frequently prescribed for the treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. In Alzheimer's disease, butyrylcholinesterase (BChE) activity increases with disease progression and may replace acetylcholinesterase function. The most frequent polymorphism of BChE is the K-variant, which is associated with lower acetylcholine-hydrolyzing activity. BChE-K polymorphism has been studied in Alzheimer's disease progression and donepezil therapy, and has led to contradictory results. OBJECTIVES To determine whether BChE-K genotype predicts response to donepezil in MCI. METHODS We examined the association between BChE-K genotype and changes in cognitive function using the data collected during the ADCS vitamin E/donepezil clinical trial in MCI. RESULTS We found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in MMSE and CDR-SB scores compared to the common allele in MCI subjects treated during the 3-year trial. We found faster MMSE decline and CDR-SB rise in BChE-K homozygous individuals treated with donepezil compared to the untreated. We observed similar interactions between BChE-K genotype and steeper changes in MMSE and CDR-SB scores in APOE4 carriers treated with donepezil compared to controls. CONCLUSION BChE-K polymorphisms are associated with deleterious changes in cognitive decline in MCI patients treated with donepezil for 3 years. This indicates that BChE-K genotyping should be performed to help identify subsets of subjects at risk for donepezil therapy, like those carrying APOE4. BChE-K and APOE4 carriers should not be prescribed off-label donepezil therapy for MCI management.
TCF7L2 Expression Is Regulated by Cell Differentiation and Overfeeding in Human Adipose Tissue

ABSTRACT Aim: The TCF7L2 gene variant rs7903146 has the largest effect on type 2 diabetes risk reported in genome-wide association studies, however its role in adipose tissue development and function is unknown. We investigate the association between gene variant rs7903146 and metabolic parameters and examine in vitro and ex vivo gene expression of TCF7L2 in human adipose tissue and progenitor cells from two independent populations of young healthy men with increased risk of type 2 diabetes due to low birth weight (LBW). Design: Adipose tissue biopsies were excised from 40 healthy young men with low and normal birth weights (NBW) after a control and 5-day high-fat overfeeding diet. In another cohort including 13 LBW and 13 NBW men, adipocyte progenitor cells were isolated and cultivated. Transcriptome-wide expression was performed on RNA extracted from biopsies or cell cultures. Results: Diet-induced peripheral insulin resistance is more pronounced in carriers of the T-risk allele rs7903146, whereas no association with hepatic insulin resistance was shown. TCF7L2 expression increased during adipogenesis in isolated preadipocytes from both LBW and NBW men (p < 0.001) and correlated positively with markers of progenitor cell proliferation and maturation capacity. In the mature adipose tissue, LBW men had lower expression of TCF7L2 compared to NBW men at baseline (p = 0.03) and TCF7L2 expression was suppressed by short-term overfeeding in NBW men (p = 0.005). Conclusions: The results suggest a regulation of TCF7L2 expression during adipogenesis and in mature adipose tissue upon overfeeding, and further that young men exposed to an adverse intrauterine environment have reduced mature adipose tissue TCF7L2 expression.
Polymorphous adenocarcinoma: an overview of immunohistochemical features and insights on molecular pathology.

Polymorphous adenocarcinoma (PAC), represents a common minor salivary gland tumor (SGT) characterized by local growth, low metastatic potential and non-aggressive biologic behavior. Due to the clinical aggressiveness noted in a subset of such tumors, the former term polymorphous low-grade adenocarcinoma (PLGA) was recently revised. PAC’s clinical features and histological diversity result in clinical overlap of this entity with several other SGTs including mainly adenoid cystic carcinoma (AdCC). Differential diagnosis among the entities is crucial, in terms of tumor management and patients’ prognosis. The aim of the present review is to summarize the histological, cytological, immunohistochemical and molecular features of PAC. Histopathological examination is usually adequate for PAC differential diagnosis from other SGTs, except of AdCC. Several immunohistochemical markers including c-Kit, S-100/ MG, Mcm-2 and Integrin β-1, -3, -4, are reported to be useful diagnostic aids in borderline cases. Limitations in sample numbers and study methodology issues of the immunohistochemical PAC studies complicate the identification and selection of appropriate markers useful in the differential diagnosis. Additionally, molecular analyses of PAC specimens indicate that the PAC spectrum phenotypes result from different genotypes (protein kinase D positive; PRKD(+) and PRKD(-) tumors). PAC pathogenesis remains to be determined in each particular genotype while the convergence issue should be addressed in future studies.
Comparing clinical outcomes between two scorpion antivenom dosing strategies in children

Abstract Background and Objectives: The clinical course from scorpion envenomation can range from mild to life threatening, particularly in younger children. The F(ab’)2 antivenom currently available in the United States is extremely effective for countering the neurotoxic effects but extremely expensive. This dose comparison study assesses clinical outcomes between two antivenom dosing strategies. Methods: This was a retrospective review of medical records of pediatric patients treated in the pediatric emergency department (PED) with grade 3 or 4 envenomation requiring antivenom. Treatments rendered at two time-periods were assessed: 3-vial first dose (May 2007–August 2011) and single-vial-serial dose (September 2011–June 2016). Primary outcome was the proportion of patients who achieved complete symptom resolution within 4 h post antivenom dose. Results: One hundred and forty-one children met entry criteria, 76 in 3-vial first dose and 65 in single-vial-serial dose. Median age was 4 years (Q1:2–Q3:7), 56.2% males. There were no demographic and differences in clinical severity at presentation between the two dosing groups. All children, irrespective of group assignment, achieved the primary end-point of symptom resolution within 4 h. Median time to complete resolution of symptoms was longer for the single-vial-serial-dosing group vs. the 3-vial-first dose group [90 min (Q1:63–Q3:124) vs. 62 min (Q1:40–Q3:90), p = 0.002]. There were no statistically significant differences between the two groups regarding clinical outcomes including PED discharge, intubation, hospitalization, or death. Conclusion: In this retrospective analysis, children in both single-vial-serial dosing group, and 3-vial-full dosing group, achieved symptom resolution within 4 h of initiating therapy with no additional complications or adverse clinical outcomes.
The role of the nasal valve in patients with obstructive sleep apnea syndrome

The nasal valve area has the minimal cross-sectional area of the upper airways. A problem at this level may easily induce impaired breathing. Obstructive sleep apnea syndrome (OSAS) is a common disorder. It has been reported that nasal obstruction may be associated with OSAS. The aim of this study was to investigate the role of nasal valve in a group of OSAS patients. Polysomnography was performed. Patients with bilateral valve incontinence had lower SaO2-nadir than patients with unilateral (or no) one. In conclusion, the present study demonstrates that a bilateral nasal valve incontinence is associated with more severe nocturnal respiratory pattern in patients with OSAS. (www.actabiomedica.it)
Quality improvement strategies to prevent falls in older adults: a systematic review and network meta-analysis.

BACKGROUND Falls are a common occurrence and the most effective quality improvement (QI) strategies remain unclear. METHODS We conducted a systematic review and network meta-analysis (NMA) to elucidate effective quality improvement (QI) strategies for falls prevention. Multiple databases were searched (inception-April 2017). We included randomised controlled trials (RCTs) of falls prevention QI strategies for participants aged ≥65 years. Two investigators screened titles and abstracts, full-text articles, conducted data abstraction and appraised risk of bias independently. RESULTS A total of 126 RCTs including 84,307 participants were included after screening 10,650 titles and abstracts and 1210 full-text articles. NMA including 29 RCTs and 26,326 patients found that team changes was statistically superior in reducing the risk of injurious falls relative to usual care (odds ratio [OR] 0.57 [0.33 to 0.99]; absolute risk difference [ARD] -0.11 [95% CI, -0.18 to -0.002]). NMA for the outcome of number of fallers including 61 RCTs and 40 128 patients found that combined case management, patient reminders and staff education (OR 0.18 [0.07 to 0.47]; ARD -0.27 [95% CI, -0.33 to -0.15]) and combined case management and patient reminders (OR, 0.36 [0.13 to 0.97]; ARD -0.19 [95% CI, -0.30 to -0.01]) were both statistically superior compared to usual care. CONCLUSIONS Team changes may reduce risk of injurious falls and a combination of case management, patient reminders, and staff education, as well as case management and patient reminders may reduce risk of falls. Our results can be tailored to decision-maker preferences and availability of resources. SYSTEMATIC REVIEW REGISTRATION PROSPERO (CRD42013004151).
Analysis of Salivary Glands and Saliva from Aedes albopictus and Aedes aegypti Infected with Chikungunya Viruses

Chikungunya virus (CHIKV) is a medically important mosquito-borne virus transmitted to humans by infected Aedes (Stegomyia) species. In 2013–2014, Ae. aegypti transmitted CHIKV to humans in the Caribbean and in 2005–2006, Ae. albopictus transmitted CHIKV on La Réunion Island (Indian Ocean basin). CHIKV LR2006 OPY1 from the La Réunion epidemic was associated with a mutation (E1:A226V) in the viral E1 glycoprotein that enhanced CHIKV transmission by Ae. albopictus. CHIKV R99659 from the Caribbean outbreak did not have the E1:A226V mutation. Here, we analyzed the salivary glands and saliva of Ae. albopictus strains from New Jersey, Florida, Louisiana and La Réunion after infection with each virus to determine their transmission potential. We infected the Ae. albopictus strains with blood meals containing 3–7 × 107 PFU/mL of each virus and analyzed the mosquitoes nine days later to maximize infection of their salivary glands. All four Ae. albopictus strains were highly susceptible to LR2006 OPY1 and R99659 viruses and their CHIKV disseminated infection rates (DIR) were statistically similar (p = 0.3916). The transmission efficiency rate (TER) was significantly lower for R99659 virus compared to LR2006 OPY1 virus in all Ae. albopictus strains and Ae. aegypti (Poza Rica) (p = 0.012) suggesting a salivary gland exit barrier to R99659 virus not seen with LR2006 OPY1 infections. If introduced, LR2006 OPY1 virus poses an increased risk of transmission by both Aedes species in the western hemisphere.
Diagnostic performance of optical coherence tomography angiography in glaucoma: a systematic review and meta-analysis

Background Compared with current imaging methods, the diagnostic performance and the advantages and limitations of optical coherence tomography angiography (OCTA) remain unclear. We performed a systematic review and meta-analysis of studies investigating vessel density (VD) in patients with glaucoma using OCTA. Methods We conducted a literature search on PubMed, Scopus, Web of Science, ISI Conference Proceedings and Google Scholar, along with a manual search, from January 2006 to March 2018. We included prospective studies that used OCTA to compare the VD in glaucomatous eyes with healthy control eyes. Results Of 3045 screened articles, 24 were included in a broad characterisation and 18 in the meta-analysis. We observed a statistically significant reduction in the mean peripapillary VD (MPVD) in glaucoma (MPVD: 57.53%, 95% CI 52.60 to 62.46, p< 0.001) compared with controls (MPVD: 65.47%, 95% CI 59.82 to 71.11; standardised mean difference [SMD], –1.41, 95% CI –1.62 to –1.20, p< 0.001) for 888 glaucomatous and 475 healthy eyes, and also in the mean-whole optic nerve image VD (SMD, –9.63, 95% CI –10.22 to –9.03, p<0.001), mean inside-disc VD (SMD, − 9.51, 95% CI –12.66 to –6.36, p<0.05) and mean parafoveal VD (SMD, –3.92, 95% CI –4.73 to –3.12, p<0.001). Subgroup analyses revealed a significant difference in the MPVD across glaucoma subtypes and OCTA devices. Conclusion This suggests the diagnostic utility of OCTA in detecting glaucomatous eyes; however, further longitudinal prospective studies are welcomed to characterise vascular changes in glaucoma.
GOLDEN2-LIKE Transcription Factors Regulate WRKY40 Expression in Response to Abscisic Acid1[OPEN]

The GARP (Golden2, ARR-B, Psr1) family transcription factors GOLDEN2-LIKE 1 and -2 (GLK1/2) modulate the ABA response. Arabidopsis (Arabidopsis thaliana) GARP (Golden2, ARR-B, Psr1) family transcription factors, GOLDEN2-LIKE1 and -2 (GLK1/2), function in different biological processes; however, whether and how these transcription factors modulate the response to abscisic acid (ABA) remain unknown. In this study, we used a glk1 glk2 double mutant to examine the role of GLK1/2 in the ABA response. The glk1 glk2 double mutant displayed ABA-hypersensitive phenotypes during seed germination and seedling development and an osmotic stress-resistant phenotype during seedling development. Genome-wide RNA sequencing analysis of the glk1 glk2 double mutant revealed that GLK1/2 regulate several ABA-responsive genes, including WRKY40, in the presence of ABA. Chromatin immunoprecipitation and gel retardation assays showed that GLK1/2 directly associate with the WRKY40 promoter via the recognition of a consensus sequence. Additionally, RNA sequencing analysis of the glk1 glk2 double mutant and wrky40 single mutant revealed that GLK1/2 and WRKY40 control a common set of downstream target genes in response to ABA. Furthermore, results of a genetic interaction test showed that the glk1 glk2 wrky40 triple mutant displayed similar ABA hypersensitivity to the wrky40 single mutant and the glk1 glk2 double mutant, while the glk1 glk2 wrky40 abi5-c (ABI5 CRISPR/Cas9 mutant) quadruple mutant displayed similar ABA hyposensitivity to the abi5-7 single mutant. Based on these results, we propose that the GLK1/2-WRKY40 transcription module plays a negative regulatory role in the ABA response.
Necroptosis and Apoptosis Contribute to Cisplatin and Aminoglycoside Ototoxicity

Ototoxic side effects of cisplatin and aminoglycosides have been extensively studied, but no therapy is available to date. Sensory hair cells, upon exposure to cisplatin or aminoglycosides, undergo apoptotic and necrotic cell death. Blocking these cell death pathways has therapeutic potential in theory, but incomplete protection and lack of therapeutic targets in the case of necrosis, has hampered the development of clinically applicable drugs. Over the past decade, a novel form of necrosis, termed necroptosis, was established as an alternative cell death pathway. Necroptosis is distinguished from passive necrotic cell death, in that it follows a cellular program, involving the receptor-interacting protein kinase (RIPK) 1 and RIPK3. In this study, we used pharmacological and genetic interventions in the mouse to test the relative contributions of necroptosis and caspase-8-mediated apoptosis toward cisplatin and aminoglycoside ototoxicity. We find that ex vivo, only apoptosis contributes to cisplatin and aminoglycoside ototoxicity, while in vivo, necroptosis as well as apoptosis are involved in both sexes. Inhibition of necroptosis and apoptosis using pharmacological compounds is thus a viable strategy to ameliorate aminoglycoside and cisplatin ototoxicity. SIGNIFICANCE STATEMENT The clinical application of cisplatin and aminoglycosides is limited due to ototoxic side effects. Here, using pharmaceutical and genetic intervention, we present evidence that two types of programmed cell death, apoptosis and necroptosis, contribute to aminoglycoside and cisplatin ototoxicity. Key molecular factors mediating necroptosis are well characterized and druggable, presenting new avenues for pharmaceutical intervention.
Balance Testing Following Concussion: Postural Sway versus Complexity Index

Although postural control deficits are common following a concussion, the current clinical assessments for postural control tend to resolve within 3 to 10 days after injury. There is a lack of sensitive tools to examine subtle changes in postural control during the recovery phase following sports‐related concussion. Only a limited number of studies have examined nonlinear dynamics of postural control; no study has examined this metric longitudinally during the recovery phase following a sports‐related concussion.
The role of serum nuclear factor erythroid 2-related factor 2 in childhood bronchial asthma

Abstract Background: Asthma is one of the most common chronic airway disease of childhood. Poor asthma control has been associated with antioxidant deficiencies. Objective: To assess the association of bronchial asthma in Egyptian children with serum nuclear factor erythroid 2–related factor2 (NRF2) and its relation to disease severity. Subjects and methods: The study included 60 asthmatic children with comparable 60 controls (age ranged from 6-16 years). Subjects were classified according to the severity of asthma into mild or moderate asthma in group I, and severe asthma in group II. Antioxidant markers including superoxide-dismutase (SOD), glutathione peroxidase (GPX) and NRF2 were assessed once in blood and serum of both subjects and controls. Results: Mean serum NRF2 and GPX were significantly lower in asthmatic group than controls group (26.36 ± 4.18 pg/mL and 5.76 ± 0.81 mU/mL vs 29.05 ± 3.87 and 6.23 ± 0.97 respectively, p < 0.05). No significant difference was detected regarding SOD (p > 0.05). In severe bronchial asthma, mean serum NRF2 and GPX were significantly lower than in mild and moderate asthma (24.29 ± 1.86 pg/mL and 5.56 ± 0.67 mU/mL vs 27.95 ± 4.77 and 6.03 ± 0.90 respectively, p < 0.05). No significant difference was found in SOD regarding severity of bronchial asthma. Low NRF2 was the only predictor of the severity of bronchial asthma (OR = 0.749 and 95% CI 0.595 – 0.942). Conclusion: The pathogenesis of childhood bronchial asthma may be associated with low serum NRF2 which may be a strong predictor of the disease severity.