Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum GFAP differentiates Alzheimer’s disease from frontotemporal dementia and predicts MCI-to-dementia conversion

Objective Reactive astrogliosis is a hallmark of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) but differences between the diseases and time course are unclear. Here, we used serum levels of the astroglial marker glial fibrillary acidic protein (GFAP) to investigate differences in patients with AD dementia, mild cognitive impairment (MCI)-AD and behavioural variant FTD (bvFTD). Methods This multicentre study included serum samples from patients diagnosed with AD dementia (n=230), MCI-AD (n=111), bvFTD (n=140) and controls (n=129). A subgroup of patients with MCI-AD (n=32) was longitudinally followed-up for 3.9±2.6 years after sample collection. Serum levels of GFAP, neurofilament light chain (NfL) and pTau181 were measured by Simoa (Quanterix) and Ella (ProteinSimple). Results In total, samples from 610 individuals from four clinical centres were investigated in this study. Serum GFAP levels in AD dementia were increased (median 375 pg/mL, IQR 276–505 pg/mL) compared with controls (167 pg/mL, IQR 108–234 pg/mL) and bvFTD (190 pg/mL, IQR 134–298 pg/mL, p<0.001). GFAP was already increased in the early disease phase (MCI-AD, 300 pg/mL, IQR 232–433 pg/mL, p<0.001) and was higher in patients with MCI-AD who developed dementia during follow-up (360 pg/mL, IQR 253–414 pg/mL vs 215 pg/mL, IQR 111–266 pg/mL, p<0.01, area under the curve (AUC)=0.77). Diagnostic performance of serum GFAP for AD (AUC=0.84, sensitivity 98%, specificity 60%, likelihood ratio 2.5) was comparable to serum pTau181 (AUC=0.89, sensitivity 80%, specificity 87%, likelihood ratio 6.0) but superior to serum NfL (AUC=0.71, sensitivity 92%, specificity 49%, likelihood ratio 1.8). Conclusions Our data indicate a different type of reactive astrogliosis in AD and bvFTD and support serum GFAP as biomarker for differential diagnosis and prediction of MCI-to-dementia conversion.
Differentially Expressed Genes in Period 2-Overexpressing Mice Striatum May Underlie Their Lower Sensitivity to Methamphetamine Addiction-Like Behavior

Previous reports have demonstrated that genetic mechanisms greatly mediate responses to drugs of abuse, including methamphetamine (METH). The circadian gene Period 2 (Per2) has been previously associated with differential responses towards METH in mice. While the behavioral consequences of eliminating Per2 have been illustrated previously, Per2 overexpression has not yet been comprehensively described; although, Per2-overexpressing (Per2 OE) mice previously showed reduced sensitivity towards METH-induced addiction-like behaviors. To further elucidate this distinct behavior of Per2 OE mice to METH, we identified possible candidate biomarkers by determining striatal differentially expressed genes (DEGs) in both drug-naïve and METH-treated Per2 OE mice relative to wild-type (WT), through RNA sequencing. Of the several DEGs in drug naïve Per2 OE mice, we identified six genes that were altered after repeated METH treatment in WT mice, but not in Per2 OE mice. These results, validated by quantitative real-time polymerase chain reaction, could suggest that the identified DEGs might underlie the previously reported weaker METH-induced responses of Per2 OE mice compared to WT. Gene network analysis also revealed that Asic3, Hba-a1, and Rnf17 are possibly associated with Per2 through physical interactions and predicted correlations, and might potentially participate in addiction. Inhibiting the functional protein of Asic3 prior to METH administration resulted in the partial reduction of METH-induced conditioned place preference in WT mice, supporting a possible involvement of Asic3 in METH-induced reward. Although encouraging further investigations, our findings suggest that these DEGs, including Asic3, may play significant roles in the lower sensitivity of Per2 OE mice to METH.
Cyber Code Intelligence for Android Malware Detection

Evolving Android malware poses a severe security threat to mobile users, and machine-learning (ML)-based defense techniques attract active research. Due to the lack of knowledge, many zero-day families’ malware may remain undetected until the classifier gains specialized knowledge. The most existing ML-based methods will take a long time to learn new malware families in the latest malware family landscape. Existing ML-based Android malware detection and classification methods struggle with the fast evolution of the malware landscape, particularly in terms of the emergence of zero-day malware families and limited representation of single-view features. In this article, a new multiview feature intelligence (MFI) framework is developed to learn the representation of a targeted capability from known malware families for recognizing unknown and evolving malware with the same capability. The new framework performs reverse engineering to extract multiview heterogeneous features, including semantic string features, API call graph features, and smali opcode sequential features. It can learn the representation of a targeted capability from known malware families through a series of processes of feature analysis, selection, aggregation, and encoding, to detect unknown Android malware with shared target capability. We create a new dataset with ground-truth information regarding capability. Many experiments are conducted on the new dataset to evaluate the performance and effectiveness of the new method. The results demonstrate that the new method outperforms three state-of-the-art methods, including: 1) Drebin; 2) MaMaDroid; and 3) $N$ -opcode, when detecting unknown Android malware with targeted capabilities.
Habitual Phytoestrogen Intake is Associated with Breast Composition in Girls at 2 Years after Menarche Onset.

BACKGROUND High phytoestrogen intake during adolescence is associated with a reduced risk of breast cancer(BC). Breast density(BD) is a strong predictor of BC and can be considered an early marker. We aim to assess the association between the mean habitual intake of isoflavones, lignans, and total phytoestrogens intake during puberty until 2y after menarche onset and absolute fibroglandular volume (AFGV) and percentage of fibroglandular volume (%FGV) in Hispanic girls at the end of puberty. METHODS Longitudinal study set up in the Growth and Obesity Chilean Cohort Study (GOCS). We included 329 girls with dietary data (multiple 24-hours recalls) from puberty until 2y after menarche onset(81% had 2-4 recalls). Two international datasets were used to estimate isoflavones, lignans and total phytoestrogens in the diet. Breast composition was measured by dual energy x-ray absorptiometry at 2y after menarche. Multiple linear regression models were used to assess the association between isoflavones, lignans and total phytoestrogens intake and AFGV and %FGV. RESULTS The average total phytoestrogen intake was 1mg/day and %FGV was 50.7%(sd=15.2) and AFGV 218.8cm3 (sd=79.3). An inverse association was found between consumption of isoflavones and AFGV, as well as, with total phytoestrogens [Q4 vs Q1 adjusted model ß=-49.2cm3, 95%CI(-85.5,-13.0)]. CONCLUSIONS Girls with a higher intake of total phytoestrogens and isoflavones during puberty until 2y after menarche onset had significantly lower AFGV. IMPACT Although the intake of phytoestrogens is low in western populations, higher consumption of them during a critical period of life like puberty could be beneficial to reduce BC during adulthood.
Analysis of prescribing error and pharmacist’s intervention on obstetrics and gynaecology outpatient prescriptions in a Malaysian tertiary hospital

Abstract Prescribing error in obstetrics and gynaecology (O&G) poses harm to women and potentially to the foetus and new born. Pharmacists’ interventions have been reported to prevent prescribing error from reaching the patients. Little is reported on the magnitude of prescribing error and pharmacist intervention in a subspecialised outpatient O&G setting. This study aimed to identify the prevalence of prescribing error and pharmacists’ interventions at the O&G outpatient setting. This retrospective study involved screening of prescriptions for commission and omission errors. Acceptance, clinical significance and rationale for pharmacists’ interventions were analysed. Of the 3883 prescriptions screened, 359 (9.2%) prescriptions contained prescribing error, mainly (52.4%) due to commission errors. Among the 395 interventions performed by the pharmacists, 207 (52.4%) were recorded for omission errors. All the interventions were accepted by the prescribers with 65.1% were categorised as ‘very significant’. About 54% of the interventions were conducted to optimise treatment outcome. The prevalence of prescribing error and pharmacists’ interventions on O&G outpatient prescriptions was found to be substantial in this study. Standard prescription writing guideline should be routinely regulated, monitored and educated among healthcare professionals. Impact Statement What is already known on this subject? Prescribing error rate in O&G was found lowest in outpatient setting as compared to inpatient and high risk settings. Pharmacists’ intervention performed at the centralised inpatient pharmacy unit or on-ward has shown to reduce prescribing error in inpatient settings. What do the results of this study add? This study identified that the prescribing error rate in a subspecialised outpatient O&G setting was within the range reported in high risk O&G settings. The number of prescriptions to pharmacists’ intervention ratio of 9.8:1 was reported. What are the implications of these findings for clinical practice and/or further research? Further research, preferably qualitative in nature, is recommended to explore, identify and address the factors that may hinder clear, accurate and complete prescription writing practices.
The antimicrobial systems of Streptococcus suis promote niche competition in pig tonsils

ABSTRACT Streptococcus suis can cause severe infections in pigs and humans. The tonsils of pigs are major niches for S. suis, and different serotypes of S. suis can be found in the same tonsil. Pig tonsil colonization by S. suis is believed to be an important source of infection for humans and pigs. However, how S. suis competes for a stable tonsil niche is unknown. Here, we found that S. suis strain WUSS351, isolated from a healthy pig tonsil, is virulent and multidrug-resistant. The ABC transporter system SstFEG, conferring resistance to bacitracin, was reported to confer a competitive survival advantage in vivo. In addition, strain WUSS351 has several antimicrobial systems, including a novel type VII secretion system (T7SS), lantibiotic bacteriocin, and lactococcin972-like bacteriocin Lcn351. Bacterial competition experiments demonstrated T7SS-mediated cell contact-dependent antagonism of S. suis. Antibacterial activity analysis and 16S rRNA gene sequencing of the culture-independent and culture-dependent pig tonsillar microbiome revealed that Lcn351 mainly targets S. suis, one of the core microbiomes in pig tonsils. Taken together, our results revealed the mechanism of the stable persistence of S. suis in the tonsil niche, which might have important implications for S. suis epidemiology, potentially influencing strain prevalence and disease progression.
Association of Open vs Robot-Assisted Radical Cystectomy With Mortality and Perioperative Outcomes Among Patients With Bladder Cancer in Sweden

Key Points Question What are the perioperative, safety, and survival outcomes of robot-assisted laparoscopic radical cystectomy (RARC) with intracorporeal urinary diversion compared with open radical cystectomy (ORC)? Findings This cohort study included 3169 patients undergoing cystectomy for bladder cancer between 2011 and 2018 in Sweden. After propensity score matching, patients who underwent RARC had lower overall mortality rate, fewer high-grade complications, and more favorable perioperative outcomes compared with those who underwent ORC. Meaning These findings suggest that in spite of the technically complex nature of the fully intracorporeal approach, nationwide implementation is feasible, with beneficial outcomes for patients with bladder cancer.
Combination of Lidocaine and IL-1Ra Is Effective at Reducing Degradation of Porcine Cartilage Explants

Background: Posttraumatic inflammation after joint injury, ranging from sprains to articular fracture, contributes to the development of arthritis, and the administration of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) is a potential intervention to mitigate this response. Although IL-1Ra mitigates cartilage degenerative changes induced by IL-1, lidocaine is used for local pain management in acute joint injury. Intra-articular delivery of both drugs in combination would be a novel and possibly disease–modifying treatment. However, it is not known whether the interaction with lidocaine at clinical concentrations (1%) would alter the efficacy of IL-1Ra to protect cartilage from the catabolic effects of IL-1. Hypothesis: Treatment of articular cartilage with IL-1Ra in combination with a clinically relevant concentration of lidocaine (1%) will inhibit the catabolic effects of IL-1α in a manner similar to treatment with IL-1Ra alone. Study Design: Controlled laboratory study. Methods: Fresh porcine cartilage explants were harvested, challenged with IL-1α, and incubated for 72 hours with IL-1Ra or a combination of IL-1Ra and lidocaine. The primary outcome was total sulfated glycosaminoglycan (sGAG) release. Additional experiments assessed the effect of storage temperature and premixing of IL-1Ra and lidocaine on sGAG release. All explants were histologically assessed for cartilage degradation using a modified Mankin grading scale. Results: The combination of IL-1Ra and lidocaine, premixed at various time points and stored at room temperature or 4°C, was as effective as IL-1Ra alone at inhibiting IL-1α–mediated sGAG release. Mankin histopathology scores supported these findings. Conclusion: Our hypothesis was supported, and results indicated that the combination of IL-1Ra and lidocaine was as efficacious as IL-1Ra treatment alone in acutely mitigating biological cartilage injury due to IL-1α in an explant model. Clinical Significance: The combination of IL-1Ra and lidocaine is stable when reagents are stored in advance of administration at varying temperatures, providing clinically relevant information about storage of medications. The ability to premix and store this drug combination for intra–articular delivery may provide a novel treatment after joint injury to provide pain relief and block inflammation–induced catabolism of joint tissues.
Stress, anxiety and depression levels in pregnancy: outpatient versus inpatient

Abstract Objective To compare stress, anxiety and depression levels among 3 groups of pregnant women: 1) low-risk outpatient (LRO), 2) high-risk outpatient (HRO), and 3) inpatient (IP). Methods This was a cross-sectional study using validated instruments. Inclusion criteria were pregnancies 23–37 weeks and maternal age > 18 years. The primary outcome was mean/median scores of Perceived Stress Scale (PSS), State Trait Anxiety Inventory (STAI), and Edinburgh Depression Scale (EDS). Secondary outcome was rate of abnormal scores. Results Among 190 women approached, 180 (95%) participated, with 60 (33%) in each group. Mean PSS scores (range 0–40) significantly increased from LRO (12.0, standard deviation [SD] 7.8) to HRO (14.7, SD 7.9) to IP (15.6, SD 8.2); p = . 04. Mean STAI scores (range 20–80) also significantly increased from LRO (32.0, SD 11.1) to HRO (35.8, SD 11.9) to IP (40.9, SD 13.1); p < . 01. Abnormal anxiety (STAI ≥ 40) was present in 40% of women and significantly higher among IP compared to LRO (56% vs 25%; RR 2.24, 95% CI 1.36–3.67; aRR 2.24, 95% CI 1.34–3.74). Conclusion Stress and anxiety scores significantly differ in LRO, HRO, and IP women. While depression screening is common postpartum, screening for stress, anxiety and depression prenatally may be beneficial.
A Pharmacokinetic Analysis of Tobramycin in Patients Less than Five Years of Age with Cystic Fibrosis: Assessment of Target Attainment with Extended-Interval Dosing through Simulation

Extended interval dosing of tobramycin is recommended for treatment of pulmonary exacerbations in adults and older children with cystic fibrosis (CF), but data are limited in patients less than 5 years of age. We performed a retrospective population pharmacokinetic (PK) analysis of hospitalized children with CF <5 years of age prescribed intravenous tobramycin for a pulmonary exacerbation from March 2011 to September 2018 at our hospital. ABSTRACT Extended interval dosing of tobramycin is recommended for treatment of pulmonary exacerbations in adults and older children with cystic fibrosis (CF), but data are limited in patients less than 5 years of age. We performed a retrospective population pharmacokinetic (PK) analysis of hospitalized children with CF <5 years of age prescribed intravenous tobramycin for a pulmonary exacerbation from March 2011 to September 2018 at our hospital. Children with normal renal function who had ≥1 tobramycin concentration available were included. Nonlinear mixed effects population PK modeling was performed using NONMEM using data from the first 48 h of tobramycin treatment. Monte Carlo simulations were implemented to determine the fraction of simulated patients that met published therapeutic targets with regimens of 10–15 mg/kg/day once-daily dosing. Fifty-eight patients received 111 tobramycin courses (range 1–9/patient). A two-compartment model best described the data. Age, glomerular filtration rate, and vancomycin coadministration were significant covariates on tobramycin clearance. The typical values of clearance and central volume of distribution were 0.252 L/hr/kg^0.75 and 0.308 L/kg, respectively. No once-daily regimens achieved all pre-specified targets simultaneously in >75% of simulated subjects. A dosage of 13 mg/kg/dose best met the predefined targets of Cmax >25 mg/L and AUC24 of 80–120 mg·h/L. Based on our population PK analysis and simulations, once-daily dosing of tobramycin would not achieve all therapeutic goals in young patients with CF. However, extended-interval dosing regimens may attain therapeutic targets in the majority of young patients.
Persistent storage symptoms following Y‐V plasty reconstruction for the treatment of refractory bladder neck contracture

Refractory bladder neck contracture (BNC) following transurethral prostatectomy is rare and difficult to manage. Success rate of endoscopic treatment decline considerably after repeated treatments. Bladder neck reconstruction are often the last resort to treat refractory BNC failing endoscopic treatments. In general, experience is limited with this type of bladder neck reconstruction, particularly in adult patients. This study aims to determine the success rate, functional and patient‐reported outcomes (PRO) of open Y‐V plasty in treatment of refractory BNC after transurethral prostatectomy. The study also aims to determine the rate, and potential predictors of persistent storage symptoms after Y‐V plasty.
Effects of different modalities of afferent stimuli of the lumbo‐sacral area on control of lumbar paravertebral muscles

Somatosensory feedback to the central nervous system is essential to plan, perform and refine spine motor control. However, the influence of somatosensory afferent input from the trunk on the motor output to trunk muscles has received little attention. The objective was to compare the effects of distinct modalities of afferent stimulation on the net motoneuron and corticomotor excitability of paravertebral muscles. Fourteen individuals were recruited. Modulation of corticospinal excitability (motor‐evoked potential [MEP]) of paravertebral muscles was measured when afferent stimuli (cutaneous noxious and non‐noxious, muscle contraction) were delivered to the trunk at 10 intervals prior to transcranial magnetic stimulation. Each peripheral stimulation was applied alone, and subsequent electromyography (EMG) modulation was measured to control for net motoneuron excitability. MEP modulation and MEP/EMG ratio were used as measures of corticospinal excitability with and without control of net motoneuron excitability, respectively. MEP and EMG modulation were smaller after evoked muscle contraction than after cutaneous noxious and non‐noxious stimuli. MEP/EMG ratio was not different between stimulation types. Both MEP and EMG amplitudes were reduced after evoked muscle contraction, but not when expressed as MEP/EMG ratio. Noxious and non‐noxious stimulation had limited impact on all variables. Distinct modalities of peripheral afferent stimulation of the lumbo‐sacral area differently modulated responses of paravertebral muscles, but without an influence on corticospinal excitability with control of net motoneuron excitability. Muscle stimulation reduced paravertebral activity and was best explained by spinal mechanisms. The impact of afferent stimulation on back muscles differs from the effects reported for limb muscles.
Voice your values, a tailored advance care planning intervention in persons living with mild dementia: A pilot study.

BACKGROUND In the early stage of dementia, persons living with dementia (PLwD) can identify their values and wishes for future care with a high degree of accuracy and reliability. However, there is a paucity of research to guide best practices on how best to incorporate advance care planning (ACP) in older adults diagnosed with mild dementia and therefore only a minority of these individuals participate in any ACP discussions. We developed an intervention called Voice Your Values (VYV) that healthcare professionals can implement to identify and document the values of PLwD and their trusted individuals such as friends or family. PURPOSE This single-group pre-test and post-test design aimed to determine the feasibility, acceptability, and preliminary efficacy of the VYV intervention. METHODS A convenience sample of 21 dyads of PLwD and their trusted individuals were recruited from five outpatient geriatric clinics. The tailored VYV intervention was delivered to the dyads over two sessions using videoconferencing. RESULTS In terms of feasibility, the recruitment rate was lower (52%) than the expected 60%; the retention rate was high at 94%, and the intervention fidelity was high based on the audit of 20% of the sessions. In terms of preliminary efficacy, PLwD demonstrated improvement in ACP engagement (p = <0.01); trusted individuals showed improvements in decision-making confidence (p = 0.01) and psychological distress (p = 0.02); whereas a minimal change was noted in their dementia knowledge (p = 0.22). CONCLUSION Most of the feasibility parameters were met. A larger sample along with a control group, as well as a longitudinal study, are requisite to rigorously evaluate the efficacy of the promising VYV intervention. There is emerging evidence that people living with mild dementia can effectively participate in identifying and expressing their values and wishes for future care.