Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts

Introduction: Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety of tofacitinib have been shown in several randomized clinical trials. The study presented here aimed to assess the clinical tolerability and effectiveness of tofacitinib among RA patients in real life. Methods: Consecutive patients between January 2015 and April 2017 with RA who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria were included in a prospectively designed analysis of retrospective data. Patients were initiated on tofacitinib 5 mg bid. The primary objective was to analyze the safety of tofacitinib in a real-life cohort. Safety was assessed by the reasons to stop tofacitinib during follow up and changes of liver enzymes, hemoglobin, and creatinine. The secondary outcome was to analyze the frequency of and time to achieve low disease activity (LDA) and remission as defined by 28 joint count disease activity score (DAS28). Results: A total of 144 patients were treated with tofacitinib. A total of 84.9% of patients were pre-exposed to at least one biological agent. The average DAS28 at the initiation of tofacitinib was 4.43. A total of 50.0% of patients were positive for rheumatoid factor and 49.0% for ACPA. The mean follow up was 1.22 years (range 10d–3.7a) after initiation of tofacitinib treatment. A total of 94 (64.4%) patients remained on tofacitinib during follow-up. The average time to stop tofacitinib was 190.0 days. Reasons to stop tofacitinib were: insufficient response (n = 23), gastrointestinal symptoms (n = 18), infection (n = 5), myalgia (n = 2), remission (n = 2), headache (n = 2), cough, blue finger syndrome, intolerance, heartburn, psoriasis, and increased liver enzymes (all n = 1). Increased alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2× upper limit of normal (ULN) were detected in 3.3% and 4.4% of patients, respectively. Hemoglobin decrease of >10% was detected in 15.1% of the patients and decreased lymphocytes <500/μL in 3.4%. An increase of creatinine >20% was detected in 9.4% of patients. A total of 62.9% and 50.0% of the patients achieved low disease activity (LDA) or remission after a median of 319 and 645 days, respectively. These rates were significantly higher in patients naïve to biologic agents as compared to patients pre-exposed to biologics (LDA: naïve 100% 92 d, pre-exposed 57.0% 434 d, p ≤ 0.001; remission: naïve 86.7% 132 d, pre-exposed 44.1%, 692 d, p = 0.001). Conclusions: Tofacitinib is a safe and effective treatment option for patients with RA. Tofacitinib may induce high rates of LDA and remission in patients with active disease, even after the use of one or more biologics, though the rate appeared higher in patients naïve to biologics. Tofacitinib may be a valuable option in a treat-to-target approach. Our data demonstrate that Janus kinase (JAK) inhibitors are safe and efficacious in real life patients.
Extra-Hippocampal Learning Deficits in Young Apolipoprotein E4 Mice and Their Synaptic Underpinning.

The E4 allele of apolipoprotein (apoE4) is the primary genetic risk factor for late onset Alzheimer's disease (AD), yet the exact manner in which apoE4 leads to the development of AD is undetermined. Human and animal studies report that apoE4-related memory deficits appear earlier than the AD clinical manifestation, thus suggesting the existence of early, pre-pathological, apoE4 impairments that may later lead to AD onset. While current research regards the hippocampus as the initial and primary effected locus by apoE4, we presently investigate the possibility that apoE4 innately impairs any brain area that requires synaptic plasticity. To test this hypothesis, we trained young (3-4-month-old) target-replacement apoE3 and apoE4 mice in conditioned taste aversion (CTA) acquisition and extinction learnings- hippocampus-independent learnings that are easily performed at a young age. Synaptic vesicular markers analysis was conducted in the gustatory cortex (GC), basolateral amygdala (BLA), medial prefrontal cortex (mPFC), and hippocampal CA3 to reveal underlying apoE4-related impairments. We have found that young apoE4 mice are severely impaired in CTA acquisition and extinction learning. CTA acquisition impairment was correlated with reduced vGat and vGlut levels in the BLA and GC, but not in CA3. CTA extinction was correlated with lower marker levels of synaptophysin and vGlut in the mPFC, a central region in CTA extinction. Our results support apoE4-related early-life plasticity impairments that precede the AD clinical manifestations and affect any brain area that depends on extensive plasticity; early impairments that may promote the development of AD pathologies later in life.
The association between specific activity components and depression in nursing home residents: the importance of the social component

Abstract Objectives To longitudinally explore the association between activities and depressive symptoms of nursing home (NH) residents, taking into account that each activity may contain multiple components (physical, creative, social, cognitive, and musical). Method Study with a baseline and two follow-ups (four and eight months). Participants were forty physically frail residents of four NHs in the Netherlands. Residents were interviewed about depressive symptoms (CES-D) and activities they conducted over the previous week. Three researchers independently rank ordered each activity on the degree to which it could be regarded as having physical, creative, social, cognitive, and musical components. Accounting for the rank score and the time the resident spent on that activity, residents were categorized per activity component into four levels: absent, low, medium, and high. Results Mixed models predicting depressive symptoms from individual activity components showed significant associations for the social and cognitive components. Compared with the lowest activity level, the analyses showed fewer depressive symptoms for all higher levels of the social and cognitive components. However, a mixed model adjusted for all activity components showed no unique effect of the cognitive component or other components, while the effects of the social component remained significant. The analyses did not show differences between the time points. Conclusion The results suggest that the effects of activities on depressive symptoms might be mainly explained by their social component. It is, thus, important to always stimulate social involvement and interaction when developing and applying depression interventions. However, intervention research is needed to confirm these findings.
Linear, Non-Conjugated Cyclic and Conjugated Cyclic Paraphenylene under Pressure

The n-paraphenylene family comprises chains of phenylene units linked together by C-C bonds that are between single- and double-bonded, and where n corresponds to the number of phenylene units. In this work, we compare the response of the optical properties of different phenylene arrangements. We study linear chains (LPP), cyclic systems (CPPs), and non-conjugated cyclic systems with two hydrogenated phenylenes (H4[n]CPP). Particularly, the systems of interest in this work are [6]LPP, [12]- and [6]CPP and H4[6]CPP. This work combines Raman and infrared spectroscopies with absorption and fluorescence (one- and two-photon excitations) measured as a function of pressure up to maximum of about 25 GPa. Unprecedented crystallographic pressure-dependent results are shown on H4[n]CPP, revealing intramolecular π-π interactions upon compression. These intramolecular interactions justify the H4[n]CPP singular optical properties with increasing fluorescence lifetime as a function of pressure.
The Long-Term Outcome of 3-Dimensional CT-Guided Percutaneous Radiofrequency Thermocoagulation for Tumor-Related Trigeminal Neuralgia.

BACKGROUND Percutaneous radiofrequency thermocoagulation (PRFT) has been widely used to treat trigeminal neuralgia. By querying MEDLINE, EMBASE, and the Cochrane Library, no study has reported the long-term outcome of PRFT for tumor-related trigeminal neuralgia (TRTN). OBJECTIVES In this study, we aimed to evaluate the long-term efficacy and safety of PRFT as an alternative treatment for TRTN. STUDY DESIGN A retrospective study. SETTING The interventional pain management center in Beijing Tiantan hospital. METHODS We retrospectively analyzed data of all patients who underwent PRFT applied to the Gasserian ganglion under computed tomography guidance for TRTN through a combination of available institutional electronic medical records, patient notes, and radiologic images. RESULTS Among 38 patients with PRFT treated between March 2007 and February 2018, 13 patients were men and 25 were women. All patients were evaluated as modified Barrow Neurological Institute (BNI) IV-V before the operation and had a total symptom duration of 45.55 ± 23.31 months. The mean operation duration was 59.63 ± 16.89 minutes. All patients experienced satisfactory pain relief defined as a classification of BNI I-IIIb within 3 days after PRFT. The median remission length with satisfactory pain relief was 33 (range, 4-132) months. No serious intraoperative complications, except bradycardia in 6 patients, were recorded. Postprocedure complications, including masticatory muscle weakness, were reported in 5 patients. Although all 38 patients experienced facial dysesthesia, the patients' Likert scale rating represented that quality of life significantly increased after the procedure. LIMITATIONS The small sample size may have unavoidably caused selection bias in our study. Larger prospective, randomized, multicenter trials are necessary to validate our outcomes. CONCLUSIONS PRFT is an effective and safe treatment that should be considered as an alternative for pain control in the treatment of TRTN. KEY WORDS Pain, secondary trigeminal neuralgia, radiofrequency thermocoagulation, trigeminal neuralgia.
Soft Wearable Skin-Stretch Device for Haptic Feedback Using Twisted and Coiled Polymer Actuators

Soft and integrated design can enable wearable haptic devices to augment natural human taction. This paper proposes a novel, soft, haptic finger-worn wearable device based on compliant and adhesive silicone skin and lightweight twisted and coiled polymer (TCP) actuators using ultra high molecular weight polyethylene (UHMWPE) fibers to provide lateral skin stretch sensations. Recently, silicone elastomers have been used in wearable sensors and in haptic applications for their high compliance or adhesion. TCP actuators have also demonstrated high power to weight ratios, large stroke length, simple mechanism, and inherent softness. Lateral skin stretch is sensitive to small motions and has been used for intuitive proprioceptive feedback applications. We combined these characteristics to design and manufacture a wearable, functional haptic prototype. Prototype performance was evaluated using an optical tracking system, a force gauge test bench, and compared to vibrotactile haptic feedback in a experiment with 14 healthy participants. Results showed that participant mean reaction times were comparable to those of a vibrotactile feedback system, though task completion times were longer. This paper is the first to employ TCP actuators for haptic stimulation and could serve as a foundation for future applications involving soft wearable haptics in gaming, health, and virtual reality.
Towards better evidence-informed global action: lessons learnt from the Lancet series and recent developments in physical activity and public health

In the past few decades, the field of physical activity has grown and evolved in scope, depth, visibility and impact around the world. Global progress has been observed in research and practice in physical activity regarding surveillance, health outcomes, correlates/determinants, interventions, translation and policy. The 2012 and 2016 Lancet series on physical activity provide some of the most comprehensive global analysis on various topics within physical activity. Based on the Lancet series and other key developments in the field, literature searches, and expert group meetings and consultation, we provide a global summary on the progress of, gaps in and future directions for physical activity research in the following areas: (1) surveillance and trends, (2) correlates and determinants, (3) health outcomes and (4) interventions, programmes and policies. Besides lessons learnt within each specific area, several recommendations are shared across areas of research, including improvement in measurement, applying a global perspective with a growing emphasis on low-income and middle-income countries, improving inclusiveness and equity in research, making translation an integral part of research for real-world impact, taking an ‘upstream’ public health approach, and working across disciplines and sectors to co-design research and co-create solutions. We have summarised lessons learnt and recommendations for future research as ‘roadmaps’ in progress to encourage moving the field of physical activity towards achieving population-level impact globally.
Dietary Spray-Dried Porcine Plasma Prevents Cognitive Decline in Senescent Mice and Reduces Neuroinflammation and Oxidative Stress.

BACKGROUND Aging is characterized by chronic, low-grade inflammation that correlates with cognitive decline. Dietary supplementation with spray-dried porcine plasma (SDP) reduces immune activation in rodent models of inflammation and aging. OBJECTIVE We investigated whether the anti-inflammatory properties of SDP could ameliorate age-related cognitive deterioration and preserve brain homeostasis in an aging mouse model of senescence. METHODS Male senescence-accelerated prone 8 (SAMP8) mice were used. In Experiment 1, cognitive performance (n = 10-14 mice/group) was analyzed by the novel object recognition test in 2-mo-old mice (2M group) and in mice fed a control diet or a diet supplemented with 8% SDP for 2 (4M-CTL, 4M-SDP groups) and 4 mo (6M-CTL, 6M-SDP groups). In Experiment 2, the permeability of the blood-brain barrier and junctional proteins in brain tissue was assessed, as well as synaptic density, oxidative stress markers, and inflammatory genes and proteins in mice from the 2M, 6M-CTL, and 6M-SDP groups (n = 5-11). Statistical analyses included one-factor ANOVA followed by Fisher's posthoc test. RESULTS 6M-SDP mice had better cognitive performance than 6M-CTL mice, in both short-term (P = 0.024) and long-term (P = 0.017) memory tests. In brain tissue, 6M-SDP mice showed reduced brain capillary permeability (P = 0.034) and increased ZO1 and E-cadherin expression (both P <0.04) compared with 6M-CTL mice. SDP also prevented the NFκB activation observed in 6M-CTL mice (P = 0.002) and reduced Il6 expression and hydrogen peroxide concentration (both P <0.03) observed in 6M-CTL mice. SDP also increased the concentration of IL10 (P = 0.027), an anti-inflammatory cytokine correlated with memory preservation. CONCLUSION In senescent SAMP8 mice, dietary supplementation with SDP attenuated cognitive decline and prevented changes in brain markers of neuroinflammation and oxidative stress.
Lumboperitoneal Shunt: A New Modified Surgical Technique and a Comparison of the Complications with Ventriculoperitoneal Shunt in a Single Center

Background and objectives: Hydrocephalus remains a disease requiring surgical treatment even in the modern era. Ventriculoperitoneal (VP) shunt placement is the most common treatment, whereas lumboperitoneal (LP) shunts are less commonly used due to initial reports of very high rates of complications. In the present study, we retrospectively reviewed our experience of the new two-stage procedure with LP shunt implantation to assess the complications and the results of this procedure versus VP shunt insertion. Materials and Methods: All patients from a single center who had received LP shunts using a Medtronic Strata device or VP shunts in the past six-year interval were retrospectively reviewed. The LP shunt insertion was a new two-stage procedure. We compared the three major complications and shunt revisions between the two groups, including shunt malfunction, infection, and subdural hematoma. Results: After matching the age and sex of both groups, we included 96 surgery numbers of LP shunts and 192 surgery numbers of VP shunts for comparison. In the LP shunt group, one patient (1.0%) underwent revision of the shunt due to shunt infection. In the VP shunt group, 26 surgeries (13.5%) needed revision, and 11 surgeries (5.7%) had shunt infection. Shunt malfunction occurred in 14 patients (7.3%) and all needed revisions. The revision rate showed statistically significant differences between the LP and VP shunt groups (p < 0.001). Conclusions: The recent improvements in the quality of the LP shunt device and the proficiency of the procedure has made the LP shunt a safer procedure than the VP shunt. The programmable valve can avoid overdrainage complications and reduce the revision rate. With our procedural steps, the LP shunt can be used to decrease the complications and revision rates.
Light Sensitivity Within Areas of Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Purpose To investigate residual sensitivity within geographic atrophy (GA) secondary to age-related macular degeneration. Methods Mesopic and dark-adapted (DA) cyan and red light sensitivity (Goldmann III) were investigated using fundus-controlled perimetry (microperimetry). Test points were placed within GA along an "iso-hull" with a distance of -0.645° to the atrophy boundary. The false-positive response rate was determined with suprathreshold stimuli to the optic disc (Heijl-Krakau method) and used to compute the expected sensitivity measurements for the assumption of absolute scotomata. The outermost visible retinal layer on spectral-domain optical coherence tomography at the location of each test point was determined. Results Thirty eyes of 36 patients (75.55 ± 7.93 years; 19 female) from the prospective natural history study Directional Spread in Geographic Atrophy (NCT02051998), with a total of 1380 threshold determinations were analyzed. The measured sensitivities were significantly (P < 0.01) higher than the expected values for absolute scotomata (mean ± standard error of +6.92 ± 0.86 dB for mesopic, +2.57 ± 0.56 dB for DA cyan, and +4.93 ± 0.74 dB for DA red testing). For mesopic testing and DA red testing, the presence of a residual outer nuclear layer had a significant effect on this discrepancy (P < 0.001). There was no effect of fixation stability or any other reliability index on this discrepancy. Conclusions Measured sensitivities within the inner junctional zone of GA may not be purely explained by patient-specific false-positive response rates or other reliability indices. The marked influence of the outer retinal configuration on measured sensitivity may be indicative of residual cone function within GA at the inner junctional zone.
The Impact of Bioinformatics Pipelines on Microbiota Studies: Does the Analytical “Microscope” Affect the Biological Interpretation?

Targeted metagenomics is the solution of choice to reveal differential microbial profiles (defined by richness, diversity and composition) as part of case-control studies. It is well documented that each data processing step may have the potential to introduce bias in the results. However, selecting a bioinformatics pipeline to analyze high-throughput sequencing data from A to Z remains one of the critical considerations in a case-control microbiota study design. Consequently, the aim of this study was to assess whether the same biological conclusions regarding human gut microbiota composition and diversity could be reached using different bioinformatics pipelines. In this work, we considered four pipelines (mothur, QIIME, kraken and CLARK) with different versions and databases, and examined their impact on the outcome of metagenetic analysis of Ion Torrent 16S sequencing data. We re-analyzed a case-control study evaluating the impact of the colonization of the intestinal protozoa Blastocystis sp. on the human gut microbial profile. Although most pipelines reported the same trends in this case-control study, we demonstrated how the use of different pipelines affects the biological conclusions that can be drawn. Targeted metagenomics must therefore rather be considered as a profiling tool to obtain a broad sense of the variations of the microbiota, rather than an accurate identification tool.
Association between Brachial-Ankle Pulse Wave Velocity and Microalbuminuria and to Predict the Risk for the Development of Microalbuminuria Using Brachial-Ankle Pulse Wave Velocity Measurement in Type 2 Diabetes Mellitus Patients

Brachial-ankle pulse wave velocity (baPWV) provides a useful means of assessing cardiovascular events and diabetic complications. However, the nature of associations between baPWV and microalbuminuria (MAU) and its presence in Type 2 diabetes mellitus (Type 2 DM) have rarely been investigated. This study aimed to examine the association between baPWV and MAU coupled with prediction of MAU using baPWV measurement among Type 2 DM patients. In this cross-sectional study, we enrolled 424 Type 2 DM patients who visited the cardiology and endocrinology department at a tertiary level health care facility, Republic of Korea between 1 January 2006 to 31 December 2008. Clinical and laboratory data were collected, and risk factors associated with MAU and prediction of risk for the development of MAU using baPWV measurement. The association between MAU and baPWV was examined using multivariable logistic regression analysis and predicted MAU by using receiver operating characteristic (ROC) curve analysis. Of the 424 Type 2 DM patients, 93 (21.9%) had MAU (20–200 μg/min). baPWV (cm/sec) was found to be significantly correlated with MAU levels (ug/min) (r = 0.791, p < 0.001). Further, baPWV was significantly associated MAU with higher odds ratio (adjusted odds ratio (AOR) 10.899; 95% confidence interval (CI) (4.518–26.292)). Similarly, smoking (AOR 5.736; 95% CI (1.036–31.755)), and low-density lipoprotein (LDL)-cholesterol (mg/dL) (AOR 1.017; 95% CI (1.001–1.033)) were also significantly associated with MAU. The appropriate cut-off value for baPWV to predict MAU 20 μg/min in our study was 1700 cm/sec (area under ROC curve = 0.976). This study shows that baPWV, cigarette smoking, and LDL-cholesterol are associated with MAU in Type 2 DM patients and suggests that a baPWV cut-off of 1700 cm/sec could be used to predict the presence of MAU (20 μg/min) in Type 2 DM patients in the Korean community.