Miracle-dz/UniFAR-FTUs huggingface dataset:
Elucidation of monocyte/macrophage dynamics and function by intravital imaging

Monocytes and macrophages are a diverse population of innate immune cells that play a critical role in homeostasis and inflammation. These cells are surveillant by nature and closely monitor the vasculature and surrounding tissue during states of health and disease. Given their abundance and strategic positioning throughout the body, myeloid cells are among the first responders to any inflammatory challenge and are active participants in most immune‐mediated diseases. Recent studies have shed new light on myeloid cell dynamics and function by use of an imaging technique referred to as intravital microscopy (IVM). This powerful approach allows researchers to gain real‐time insights into monocytes and macrophages performing homeostatic and inflammatory tasks in living tissues. In this review, we will present a contemporary synopsis of how intravital microscopy has revolutionized our understanding of myeloid cell contributions to vascular maintenance, microbial defense, autoimmunity, tumorigenesis, and acute/chronic inflammatory diseases.
Wingspan experience at Beijing Tiantan Hospital: new insights into the mechanisms of procedural complication from viewing intraoperative transient ischemic attacks during awake stenting for vertebrobasilar stenosis

Background and aim Intracranial vertebrobasilar artery (VBA) stenosis portends a stroke and death rate of 8.5–22.8% annually despite medical therapy. Stenting has emerged as a treatment option but also carries substantial risk. Awake stenting under local anesthesia to minimize major procedural complication was investigated. Methods Between January 2007 and December 2008, 43 of 46 consecutive patients with severe symptomatic intracranial VBA stenosis underwent elective angioplasty assisted with self-expanding Wingspan stent under local anesthesia at our institute. All data were collected prospectively. Results All 43 patients tolerated the stenting procedure under local anesthesia well. Forty-two patients (97.7%) were stented successfully. Within 30 days, there were three periprocedural strokes, including thromboembolic infarct, pontine perforator infarct and intracranial hemorrhage, without fatality. In addition, five patients had intraoperative brainstem transient ischemic attacks (TIAs) seconds after the deployment of the stent delivery system across the tortuous VBA. The symptoms and signs included impaired consciousness (n=5), dysarthria (n=3), convulsion (n=2), conjugate horizontal gaze palsy (n=2), nystagmus (n=2) and pinpoint pupils (n=1). There was angiographic evidence of VBA straightening without thromboembolism. The TIAs resolved within minutes of prompt removal of the delivery catheter. Conclusions VBA stenting under local anesthesia is feasible with a 7% periprocedural stroke risk. Awake stenting allows timely detection of intraoperative TIAs. The mechanism of intraoperative TIA appears to be stent delivery system induced VBA straightening and distortion of its vascular tree. A devastating stroke may ensue if the TIA is not detected and distortion of VBA perforators is not reversed promptly.
JAM‐A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV‐infected individuals

Monocyte transmigration across the BBB is a critical step in the development of cognitive deficits termed HAND that affect 40–70% of HIV‐infected individuals, even with successful antiretroviral therapy. The monocyte subsets that enter the CNS during HIV infection are not fully characterized. We examined PBMC from HIV‐positive individuals from 2 distinct cohorts and enumerated monocyte populations, characterized their transmigration properties across an in vitro human BBB model, and identified surface proteins critical for the entry of these cells into the CNS. We demonstrated that the frequency of peripheral blood CD14+CD16+ and CD14lowCD16+ monocytes was increased in HIV‐seropositive compared with ‐seronegative individuals, despite virologic control. We showed that CD14+CD16+ monocytes selectively transmigrated across our BBB model as a result of their increased JAM‐A and ALCAM expression. Antibody blocking of these proteins inhibited diapedesis of CD14+CD16+ monocytes but not of T cells from the same HIV‐infected people across the BBB. Our data indicate that JAM‐A and ALCAM are therapeutic targets to decrease the entry of CD14+CD16+ monocytes into the CNS of HIV‐seropositive individuals, contributing to the eradication of neuroinflammation, HAND, and CNS viral reservoirs.
Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice

Hepatic Macs, consisting of resident KCs and infiltrating monocytes/IMs, are thought to play an important role in the pathogenesis of ALD. Previous work has focused on KCs or studied hepatic Macs as one cell population. The aim of the current study is to distinguish IMs from KCs and to compare their phenotypes and functions. We show here that a 4‐week ethanol feeding of C57BL/6J mice causes recruitment of IMs into the liver. KCs and IMs can be distinguished based on their differential expression of F4/80 and CD11b. IMs can be divided further into two subsets based on their differential expression of Ly6C. KCs and two subsets of IMs were separately purified by FACS. The phagocytosis abilities and the expression profiles of genes related to various functions were compared among different populations of hepatic Macs. Ly6Clow IMs exhibit an anti‐inflammatory and tissue‐protective phenotype; in contrast, Ly6Chi IMs exhibit a proinflammatory, tissue‐damaging phenotype. The ratio of Ly6Chi/Ly6Clow increases when mice chronically fed ethanol were binged, which significantly enhanced liver injury. Moreover, upon phagocytosis of apoptotic hepatocytes, Ly6Chi IMs switch to Ly6Clow IMs. Taken together, chronic ethanol feeding induces the recruitment of two subsets of hepatic IMs, which play different or even opposite roles in regulating liver inflammation and repair. These findings may not only increase our understanding of the complex functions of Macs in the pathogenesis of ALD but also help us to identify novel therapeutic targets for the treatment of this disease.
Validating software metrics: producing quality discriminators

The author proposes a comprehensive metrics validation methodology that has six validation criteria, each of which supports certain quality functions. New criteria are defined and illustrated, including consistency, discrimination power, tracking, and repeatability. He shows that certain nonparametric statistical methods like contingency tables play an important role in evaluating metrics against the validity criteria. A detailed example emphasizing the discriminative power validity criterion is presented. <<ETX>>
Analysis of the HLA‐DR peptidome from human dendritic cells reveals high affinity repertoires and nonconventional pathways of peptide generation

Dendritic cells (DCs) are the major professional APCs of the immune system; however, their MHC‐II–associated peptide repertoires have been hard to analyze, mostly because of their scarce presence in blood and tissues. In vitro matured human monocyte‐derived DCs (MoDCs) are widely used as professional APCs in experimental systems. In this work, we have applied mass spectrometry to identify the HLA‐DR–associated self‐peptide repertoires from small numbers of mature MoDCs (∼5 × 106 cells), derived from 7 different donors. Repertoires of 9 different HLA‐DR alleles were defined from analysis of 1319 peptides, showing the expected characteristics of MHC‐II–associated peptides. Most peptides identified were predicted high binders for their respective allele, formed nested sets, and belonged to endo‐lysosomal pathway‐degraded proteins. Approximately 20% of the peptides were derived from cytosolic and nuclear proteins, a recurrent finding in HLA‐DR peptide repertoires. Of interest, most of these peptides corresponded to single sequences, did not form nested sets, and were located at the C terminus of the parental protein, which suggested alternative processing. Analysis of cleavage patterns for terminal peptides predominantly showed aspartic acid before the cleavage site of both C‐ and N‐terminal peptides and proline immediately after the cleavage site in C‐terminal peptides. Proline was also frequent next to the cut sites of internal peptides. These data provide new insights into the Ag processing capabilities of DCs. The relevance of these processing pathways and their contribution to response to infection, tolerance induction, or autoimmunity deserve further analysis.
Assessment of a sampling method for measuring safety-critical software reliability

The paper addresses the issue of using sampling to assess the reliability of safety-critical software. Several factors are considered, such as the number of test cases required, modifications in the program, determining the operational profile, generating test cases, and checking the correctness of the output. The problems are classified into two broad categories: those that can be overcome via advances in technology and those that are more fundamental in nature. The general conclusion is that, in principle, a combination of testing and verification will be successful in measuring ultrahigh software reliability. <<ETX>>
Software trustability

A measure of software dependability called trustability is described. A program p has trustability T if we are at least T confident that p is free of faults. Trustability measurement depends on detectability. The detectability of a method is the conditional probability that it will detect faults. The trustability model characterizes the kind of information needed to justify a given level of trustability. When the required information is available, the trustability approach can be used to determine strategies in which methods are combined for maximum effectiveness. It can be used to determine the minimum amount of resources needed to guarantee a required degree of trustability, and the maximum trustability that is achievable with a given amount of resources. <<ETX>>
Global perceptions of food allergy thresholds in 16 countries

Childhood food allergy is a significant public health issue with prevalence rates as high as 10% among children in some countries (1, 2). While the quality and quantity of global data on childhood food allergy have increased in recent years, knowledge on consumer perceptions of issues affecting management is lacking (3, 4). Allergic reactions to food can vary from mild to life-threatening. As a result, the standard recommendation is to strictly avoid the food allergen, which can be complicated when purchasing packaged food. The food industry in most countries is required to label the presence of the most common food allergens when they are ingredients in packaged foods; however, they may voluntarily add precautionary allergen labeling (PAL). These statements, such as ‘may contain. ’ or ‘processed in a facility that manufactures. ’, are unregulated, and it is unknown how many products with PAL actually contain trace levels. Consumers must make their own decisions on how to interpret these PAL statements, which can lead to food restrictions that affect the daily lives and well-being of consumers and caregivers (5, 6). A greater understanding of food allergen thresholds (the lowest amount of a food allergen that can cause an allergic reaction) is important to a variety of food allergy stakeholders (7). In 2011, an expert panel was assembled to establish reference doses for 11 allergenic foods as part of the VITAL (Voluntary Incidental Trace Allergen Labeling) program. The doses were obtained from clinical challenges of individuals to establish an eliciting dose for each food at which only a predicted 1–3% of the population would react (8). This study represents the first of its kind to examine differences in perceptions about food allergen thresholds and PAL from the perspective of consumers in 16 countries across the world.
Long-term clinical relevance of criteria for designating multiple sclerosis as benign after 10 years of disease

Objectives: To determine the long-term outcome of a cohort of 436 patients with multiple sclerosis (MS) seen in 1985 and long-term predictors of benign MS. Methods: The initial 1985 group of 436 patients with possible MS, including 53 benign patients, were followed for 21 years. Disability was recorded using the Expanded Disability Status Scale (EDSS). Survival from disease onset was calculated. The indicators of benign MS in the initial 1985 cohort and in the survivors in 2006 were determined. Results: Of the original 436 patients, the 21-year follow-up outcome in 397 (91%) was established. The diagnosis of MS was incorrect in 41/397 (10%) of the whole cohort and in 2/53 (4%) of the benign group. Median survival of 356 patients with MS was 43.6 years from disease onset. Of 47/51 (92%) patients with benign MS followed in 2006, 7 (15%) remained benign, 18 had died and 22 were disabled. Median survival advantage for the 47 benign patients in 1985 compared to the 88 non-benign patients, when corrected for age, was 6 years (p<0.08). In 2006, 40/356 (11%) patients had a benign outcome at a mean follow-up of 26.1 years. A benign course was significantly associated with female sex, younger age of onset and absence of motor symptoms at presentation. Conclusions: Although designating patients as having a benign course after 10 years has a poor predictive value, three factors at presentation indicate a better prognosis.
A switch in regulatory T cells through farm exposure during immune maturation in childhood

Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm‐milk exposure was partially mediated by regulatory T cells (Tregs). The aim of this study was to investigate the critical time window of the ‘asthma‐protective’ farm effect via Tregs during childhood immune maturation.
Personal computing in community organisations: expertise out of context

The objectives of community-based organisations usually differ significantly from those of more market-driven business and corporate institutions. Recent developments in information technology, such as personal computing, have been largely directed to assist the goals of market-based organisations. Personal computing has had great success in this area, and this success has led to an increasing use of personal computers in community organisations. However, attempts by outside experts to prescribe, or create, uses for computers in community organisations often fail. Four brief case studies, which draw on experiences of the Australian 'Neighbourhood House' movement, are presented. In these case studies problems are observed to have arisen through a lack of attention by expert advisors to the contexts in which Neighbourhood Houses (and similar community organisations) become involved with personal computing. These technical, social, economic and political contexts are examined in some detail.
Cognitive-behavioural intervention for self-harm: randomised controlled trial

Background Self-harm by young people is occurring with increasing frequency. Conventional in-patient and out-patient treatment has yet to be proved efficacious. Aims To investigate the efficacy of a short cognitive-behavioural therapy intervention with 90 adolescents and adults who had recently engaged in self-harm. Method Participants (aged 15–35 years) were randomly assigned to treatment as usual plus the intervention, or treatment as usual only. Assessments were completed at baseline and at 3 months, 6 months and 9 months follow-up. Results Patients who received cognitive-behavioural therapy in addition to treatment as usual were found to have significantly greater reductions in self-harm, suicidal cognitions and symptoms of depression and anxiety, and significantly greater improvements in self-esteem and problem-solving ability, compared with the control group. Conclusions These findings extend the evidence that a time-limited cognitive-behavioural intervention is effective for patients with recurrent and chronic self-harm.
Evaluation and treatment of inflammatory myopathies

The major types of idiopathic inflammatory myopathy include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune mediated necrotising myopathy (NM). These myositides appear clinically, histologically and pathogenically distinct. DM, PM and immune mediated NM are responsive to immunosuppressive therapy, in contrast with IBM which is generally refractory to therapy. Greater understanding of the pathogenic bases of these disorders should hopefully lead to better treatment. We need well designed, prospective, double blind, placebo controlled trials in order to determine the best therapeutic options for these different disorders.
Responsiveness of patient reported outcome measures in multiple sclerosis relapses: the REMS study

Objectives: To assess the responsiveness of the three most used patient reported multiple sclerosis (MS) specific questionnaires: the Functional Assessment of MS (FAMS), the MS Impact Scale (MSIS-29) and the 54 item MS Quality of Life (MSQOL-54). Design: Prospective multicentre longitudinal study on 104 MS patients treated with intravenous steroids for clinical exacerbation. Methods: Patient reported data, Expanded Disability Status Scale (EDSS) score and clinical information were collected at admission and 8 weeks later. “Internal” (distribution based) responsiveness was assessed by standardised response means (SRM). “External” (anchor based) responsiveness was assessed by receiver operating characteristic (ROC) curves in relation to corresponding changes in a pre-specified reference measure (anchor). The pre-specified anchor was patients’ self-reported recovery assessed on a 5 point Likert scale. Results: SRM was 0.39 for FAMS, 0.58 for MSIS-29 physical scale, 0.45 for MSIS-29 psychological scale, 0.71 for MSQOL-54 physical health composite and 0.57 for MSQOL-54 mental health composite. Seventy-three patients (70%) reported they had improved; physicians agreed substantially with patient assessments (kappa statistic 0.70, 95% CI 0.54 to 0.85). Areas under ROC curves differed significantly from 0.50 only for the MSIS-29 and MSQOL-54 scales where areas ranged from 0.65 (95% CI 0.53 to 0.76) for the MSIS-29 psychological scale to 0.70 (95% CI 0.58 to 0.81) for the MSQOL-54 mental health composite. Areas under ROC curves assessed using a physician based anchor were similar to the patient based areas. Conclusions: The responsiveness of the MS specific instruments was less than ideal. The MSIS-29 and MSQOL-54 were significantly more responsive, using both distribution based and anchor based approaches, than FAMS, and should be preferred in longitudinal studies.
Endovascular treatment of recurrent intracranial aneurysms with re-coiling or covered stents

Objective: To report our experiences in the treatment of recurrent intracranial aneurysms with re-coiling or covered stents. Methods: A total of 291 patients with 305 intracranial aneurysms were treated with detachable coils, and 41 (28.9%) of 142 patients with aneurysms in the internal carotid artery had a recurrent aneurysm during the follow-up period. For this study, 31 recurrent aneurysms in 31 patients who had angiograms within 6 months following retreatment with detachable coils (group A, n = 20) or covered stents (group B, n = 11) were analysed. Aneurysms were categorised as complete or incomplete occlusion via angiographic assessment and graded as full recovery, improvement, no change or deterioration via clinical assessment. Data regarding technical success, initial and final angiographic results, mortality, morbidity and final clinical outcome were collected and analysed postoperatively. Results: Coil embolisation and covered stent placement were technically successful in all recurrent aneurysms. The initial angiographic results showed complete occlusion in 11 patients (55%) in group A and in eight (72.7%) in group B (p = 0.452), and the final angiographic results exhibited complete occlusion in 10 patients (50%) in group A and in 11 (100%) in group B (p = 0.005). There were no significant differences in technique success, mortality, culminate morbidity or final clinical outcome between the two groups. Conclusions: Recurrent aneurysms after coiling can be successfully treated and occluded with re-coiling or covered stent placement. However, covered stents seem to be more effective than re-coiling with regard to complete occlusion of recurrent aneurysms.
Hemisplenial- accompanied by internal border-zone infarction: clinical relevance of the splenium of the corpus callosum as a border-zone area between anterior and posterior cerebral arteries

Infarction of the corpus callosum (CC) is rare because it receives a rich supply of blood from the anterior and posterior circulation.1 We present a patient with severe haemodynamic insufficiency (HI) of the cerebral hemisphere due to steno-occlusive disease of the bilateral internal carotid arteries (ICA). His ipsilateral hemisplenial infarction of the CC enlarged progressively. We discuss the clinical relevance of the splenium of the CC as a border-zone (BZ) area between the anterior- and posterior cerebral arteries (ACA, PCA). This 63-year-old right-handed man with a medical history of hypertension and diabetes mellitus presented with dysarthria, lack of motivation and memory difficulties. MRI showed multiple acute infarcts in the internal BZ area and a single spotty infarct in the hemisplenium of the CC on the left side (figure 1A). We considered his dysarthria to be attributable to infarction of the BZ area, but we did not know whether the infarct in the CC hemispelnium was asymptomatic or played no role in his memory disturbance. Magnetic resonance- and digital subtraction angiography (MRA, DSA) revealed occlusion of the left ICA and severe stenosis of the right cervical ICA. The capacity of the left PCA was …
Cognitive impairment predicts poststroke death in long-term follow-up

Background: Poststroke global cognitive decline and dementia have been related to poor long-term survival. Whether deficits in specific cognitive domains are associated with long-term survival in patients with ischaemic stroke is not known in detail. Methods: Patients with acute stroke subjected to comprehensive neuropsychological evaluation were included in the study (n = 409) and followed up for up to 12 years. Results: In Kaplan–Meier analysis, impairments in following cognitive domains predicted poor poststroke survival (estimated years): executive functions (48.2%) (5.8 vs 10.1 years, p<0.0001), memory (59.9%) (6.8 vs 9.3 years, p = 0.009), language (28.9%) (5.3 vs 8.6 years, p = 0.004) and visuospatial/constructional abilities (55.2%) (5.6 vs 10.1 years, p<0.0001). Low Mini Mental Status Examination (MMSE) ⩽25 (30.5%) (4.4 vs 9.3 years, p<0.0001), low education (<6 years) (31.8%) (6.4 vs 8.2 years, p = 0.003) and poor modified Rankin score (39.9%) (3.9 vs 9.7 years, p<0.0001) were also related to poor survival. In Cox regression proportional hazards analyses including age, sex and years of education as covariates, deficits in executive functions (hazard ratio (HR) 1.59, p<0.0001), memory (HR 1.31, p = 0.042), language (HR 1.33, p = 0.036) and visuospatial/constructional abilities (HR 1.82, p<0.0001) were significant predictors of poor poststroke survival. Of these, executive functions (HR 1.33, p = 0.040) as well as visuospatial/constructional abilities (HR 1.53, p = 0.004) remained as significant predictors after addition of MMSE⩽25 and poor modified Rankin score as covariates. Furthermore, cognitive impairment no dementia (CIND) was also an independent predictor of poor poststroke survival (HR 1.63, p = 0.0123). Conclusions: In patients with ischaemic stroke, cognitive impairment, particularly in executive functions, and visuospatial/constructional abilities relate to poor survival.