Miracle-dz/UniFAR-FTUs huggingface dataset:
Composite Bloom Filters for Secure Record Linkage

The process of record linkage seeks to integrate instances that correspond to the same entity. Record linkage has traditionally been performed through the comparison of identifying field values (e.g., Surname), however, when databases are maintained by disparate organizations, the disclosure of such information can breach the privacy of the corresponding individuals. Various private record linkage (PRL) methods have been developed to obscure such identifiers, but they vary widely in their ability to balance competing goals of accuracy, efficiency and security. The tokenization and hashing of field values into Bloom filters (BF) enables greater linkage accuracy and efficiency than other PRL methods, but the encodings may be compromised through frequency-based cryptanalysis. Our objective is to adapt a BF encoding technique to mitigate such attacks with minimal sacrifices in accuracy and efficiency. To accomplish these goals, we introduce a statistically-informed method to generate BF encodings that integrate bits from multiple fields, the frequencies of which are provably associated with a minimum number of fields. Our method enables a user-specified tradeoff between security and accuracy. We compare our encoding method with other techniques using a public dataset of voter registration records and demonstrate that the increases in security come with only minor losses to accuracy.
Toll-Like Receptor 7 Agonist Imiquimod in Combination with Influenza Vaccine Expedites and Augments Humoral Immune Responses against Influenza A(H1N1)pdm09 Virus Infection in BALB/c Mice

ABSTRACT Toll-like receptors (TLRs) of the innate immune system are known targets for enhancing vaccine efficacy. We investigated whether imiquimod, a synthetic TLR7 agonist, can expedite the immune response against influenza virus infection when combined with influenza vaccine. BALB/c mice were immunized intraperitoneally with monovalent A(H1N1)pdm09 vaccine combined with imiquimod (VCI) prior to intranasal inoculation with a lethal dose of mouse-adapted A(H1N1)pdm09 virus. For mice immunized 3 days before infection, the survival rates were significantly higher in the VCI group (60%, mean survival time[MST], 11 days) than in the vaccine-alone (30%; MST, 8.8 days), imiquimod-alone (5%; MST, 8.4 days), and phosphate-buffered saline (PBS) (0%; MST, 6.2 days) groups (P < 0.01). In the VCI group, 45 and 35% of the mice survived even when they were infected 2 days or 1 day after immunization. Virus-specific serum IgM, IgG, and neutralizing antibodies appeared earlier with higher geometric mean titers in the VCI group than in the control groups. The pulmonary viral load was significantly lower at all time points postinfection in the VCI, vaccine-alone, and imiquimod-alone groups than in the PBS control group (P < 0.05). The protection induced by VCI was specific for A(H1N1)pdm09 virus but not for A(H5N1) virus. Since imiquimod combined with RNase-treated vaccine is as protective as imiquimod combined with untreated vaccine, mechanisms other than TLR7 may operate in expediting and augmenting immune protection. Moreover, increased gamma interferon mRNA expression and IgG isotype switching, which are markers of the Th1 response induced by imiquimod, were not apparent in our mouse model. The mechanisms of imiquimod-induced immune protection deserve further study.
Neisseria Adhesin A Variation and Revised Nomenclature Scheme

ABSTRACT Neisseria adhesin A (NadA), involved in the adhesion and invasion of Neisseria meningitidis into host tissues, is one of the major components of Bexsero, a novel multicomponent vaccine licensed for protection against meningococcal serogroup B in Europe, Australia, and Canada. NadA has been identified in approximately 30% of clinical isolates and in a much lower proportion of carrier isolates. Three protein variants were originally identified in invasive meningococci and named NadA-1, NadA-2, and NadA-3, whereas most carrier isolates either lacked the gene or harbored a different variant, NadA-4. Further analysis of isolates belonging to the sequence type 213 (ST-213) clonal complex identified NadA-5, which was structurally similar to NadA-4, but more distantly related to NadA-1, -2, and -3. At the time of this writing, more than 89 distinct nadA allele sequences and 43 distinct peptides have been described. Here, we present a revised nomenclature system, taking into account the complete data set, which is compatible with previous classification schemes and is expandable. The main features of this new scheme include (i) the grouping of the previously named NadA-2 and NadA-3 variants into a single NadA-2/3 variant, (ii) the grouping of the previously assigned NadA-4 and NadA-5 variants into a single NadA-4/5 variant, (iii) the introduction of an additional variant (NadA-6), and (iv) the classification of the variants into two main groups, named groups I and II. To facilitate querying of the sequences and submission of new allele sequences, the nucleotide and amino acid sequences are available at http://pubmlst.org/neisseria/NadA/.
α[ 11C]Methyl-L-Tryptophan Positron Emission Tomography in Patients With Alternating Hemiplegia of Childhood

Based on previous reports suggesting a role of the neurotransmitter serotonin in the pathomechanism of alternating hemiplegia of childhood and speculation that it may be a migraine variant, we measured brain serotonin synthesis in children with alternating hemiplegia of childhood. Clinical and neurodevelopmental data, as well as standard uptake values in 25 brain regions and whole-brain serotonin synthesis capacity (unidirectional uptake rate constant or K-complex), were assessed in six patients with alternating hemiplegia of childhood (three girls and three boys; mean age = 76/12 years) using α[ 11C]methyl-L-tryptophan positron emission tomography (PET). The PET studies were performed interictally in three patients, during the ictal state in two patients, and postictally in one patient. The PET data were compared to those obtained interictally from six age-matched patients with focal epilepsy (two girls and four boys; mean age = 78/12 years) and six non-age-matched apparently normal siblings of autistic children (two girls and four boys; mean age = 911/12 years). Patients with alternating hemiplegia of childhood studied in the ictal or postictal state showed increased serotonin synthesis capacity in the frontoparietal cortex, lateral and medial temporal structures, striatum, and thalamus when compared to controls, and subjects with alternating hemiplegia of childhood studied interictally. The involvement of these brain regions was consistent with the semiology of the hemiplegic attacks. In patients with interictal studies and in the controls, the PET scans revealed similar and bilaterally symmetric regional patterns of serotonin synthesis capacity. Increased whole-brain serotonin synthesis capacity (reported in migraine subjects without aura) was not found in the alternating hemiplegia of childhood group. There was no correlation between the neurodevelopmental scores and regional standard uptake values; however, patients with a larger estimated lifetime attack number showed greater delay in communication (P = .005) and daily living skills (P = .042). These studies suggest increased regional serotonergic activity associated with attacks in alternating hemiplegia of childhood. Furthermore, the attack number may have an effect on neurodevelopmental delay, thus supporting the notion that alternating hemiplegia of childhood may be a progressive disorder. (J Child Neurol 2002;17:253-260).
A Systematic Review of Clinical Study of Bee Venom Acupuncture

Objectives : The purpose of this systematic review was to overview and evaluate the current state of the usage of bee venom acupuncture. Methods : We collected 173 articles on bee venom acupuncture(BVA) clinical study from eight electronic databases from January 2002 to June 2013. Results : BVA was used in musculoskeletal diseases for 66 %, and the chosen acupoints were various. The ratio of the reports which had collected below 10 cases was 43 %. The concomitant treatment and evaluation tools showed diversity in each article. Conclusions : Bee venom clinical study shows the lack of unity and consistent regulation, and has low clinical cases. Future studies should correct these limits and promote more varied research to develop the therapy of bee venom acupuncture.
Three Approaches to Understanding and Classifying Mental Disorder: ICD-11, DSM-5, and the National Institute of Mental Health’s Research Domain Criteria (RDoC)

The diagnosis of mental disorder initially appears relatively straightforward: Patients present with symptoms or visible signs of illness; health professionals make diagnoses based primarily on these symptoms and signs; and they prescribe medication, psychotherapy, or both, accordingly. However, despite a dramatic expansion of knowledge about mental disorders during the past half century, understanding of their components and processes remains rudimentary. We provide histories and descriptions of three systems with different purposes relevant to understanding and classifying mental disorder. Two major diagnostic manuals—the International Classification of Diseases and the Diagnostic and Statistical Manual of Mental Disorders—provide classification systems relevant to public health, clinical diagnosis, service provision, and specific research applications, the former internationally and the latter primarily for the United States. In contrast, the National Institute of Mental Health’s Research Domain Criteria provides a framework that emphasizes integration of basic behavioral and neuroscience research to deepen the understanding of mental disorder. We identify four key issues that present challenges to understanding and classifying mental disorder: etiology, including the multiple causality of mental disorder; whether the relevant phenomena are discrete categories or dimensions; thresholds, which set the boundaries between disorder and nondisorder; and comorbidity, the fact that individuals with mental illness often meet diagnostic requirements for multiple conditions. We discuss how the three systems’ approaches to these key issues correspond or diverge as a result of their different histories, purposes, and constituencies. Although the systems have varying degrees of overlap and distinguishing features, they share the goal of reducing the burden of suffering due to mental disorder.
Antibodies to a Novel Leptospiral Protein, LruC, in the Eye Fluids and Sera of Horses with Leptospira-Associated Uveitis

ABSTRACT Screening of an expression library of Leptospira interrogans with eye fluids from uveitic horses resulted in identification of a novel protein, LruC. LruC is located in the inner leaflet of the leptospiral outer membrane, and an lruC gene was detected in all tested pathogenic L. interrogans strains. LruC-specific antibody levels were significantly higher in eye fluids and sera of uveitic horses than healthy horses. These findings suggest that LruC may play a role in equine leptospiral uveitis.
PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

ABSTRACT Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD.
Filtering Out Infrequent Behavior from Business Process Event Logs

In the era of “big data”, one of the key challenges is to analyze large amounts of data collected in meaningful and scalable ways. The field of process mining is concerned with the analysis of data that is of a particular nature, namely data that results from the execution of business processes. The analysis of such data can be negatively influenced by the presence of outliers, which reflect infrequent behavior or “noise”. In process discovery, where the objective is to automatically extract a process model from the data, this may result in rarely travelled pathways that clutter the process model. This paper presents an automated technique to the removal of infrequent behavior from event logs. The proposed technique is evaluated in detail and it is shown that its application in conjunction with certain existing process discovery algorithms significantly improves the quality of the discovered process models and that it scales well to large datasets.
Evaluation of Lysine Biosynthesis as an Antifungal Drug Target: Biochemical Characterization of Aspergillus fumigatus Homocitrate Synthase and Virulence Studies

ABSTRACT Aspergillus fumigatus is the main cause of severe invasive aspergillosis. To combat this life-threatening infection, only limited numbers of antifungals are available. The fungal α-aminoadipate pathway, which is essential for lysine biosynthesis, has been suggested as a potential antifungal drug target. Here we reanalyzed the role of this pathway for establishment of invasive aspergillosis in murine models. We selected the first pathway-specific enzyme, homocitrate synthase (HcsA), for biochemical characterization and for study of its role in virulence. A. fumigatus HcsA was specific for the substrates acetyl-coenzyme A (acetyl-CoA) and α-ketoglutarate, and its activity was independent of any metal ions. In contrast to the case for other homocitrate synthases, enzymatic activity was hardly affected by lysine and gene expression increased under conditions of lysine supplementation. An hcsA deletion mutant was lysine auxotrophic and unable to germinate on unhydrolyzed proteins given as a sole nutrient source. However, the addition of partially purified A. fumigatus proteases restored growth, confirming the importance of free lysine to complement auxotrophy. In contrast to lysine-auxotrophic mutants from other fungal species, the mutant grew on blood and serum, indicating the existence of high-affinity lysine uptake systems. In agreement, although the virulence of the mutant was strongly attenuated in murine models of bronchopulmonary aspergillosis, virulence was partially restored by lysine supplementation via the drinking water. Additionally, in contrast to the case for attenuated pulmonary infections, the mutant retained full virulence when injected intravenously. Therefore, we concluded that inhibition of fungal lysine biosynthesis, at least for disseminating invasive aspergillosis, does not appear to provide a suitable target for new antifungals.
Asymptomatic 50% to 75% internal carotid artery stenosis in 288 patients: risk factors for disease progression and ipsilateral neurological symptoms.

INTRODUCTION This study identified characteristics of patients with moderate internal carotid artery stenosis that are at increased risk for disease progression. METHODS Patients with asymptomatic moderate internal carotid disease correlating to 50% to 75% diameter reduction were followed for 3 years. Progression to greater than 75% diameter reduction or presentation with focal neurological symptoms was documented. Descriptive statistics and χ(2) testing provided statistical analysis. RESULTS During follow-up, 26 (9%) developed symptoms or had an asymptomatic increase in diameter reduction to >75%. The rate of disease progression and/or development of symptoms was 5.5% at 12 months and increased to 7.2% by 24 months. Comorbidities with the highest associated event incidences were coronary artery disease (8.1%), hyperlipidemia (7.3%), and hypertension (6.7%). CONCLUSION Male patients with coronary artery disease, hyperlipidemia, and hypertension are at increased risk and are candidates for frequent screening and/or early intervention.
Outwardly Rectifying Anionic Channel from the Plasma Membrane of the Fungus Phycomyces blakesleeanus

In the present report, by using a patch clamp technique, we provide, to our knowledge, the first detailed description of an anionic channel from filamentous fungi. The characterized channel, an outwardly rectifying anionic channel (ORAC), is the most prominent feature of the cell membrane of the fungus Phycomyces blakesleeanus in the absence of energizing substrates. The unitary conductance of the channel is 11.3 0.4 pS. It is characterized by a strong voltage dependence of the open-channel probability (z ; the gating charge is 2.1 0.1), and the channel is activated by depolarization. The values of the time constants for voltage-induced activation and deactivation of 28 3 ms for a and 39 9 ms for d show that the ORAC is characterized by fast activation/deactivation kinetics. The ORAC shows strong selectivity for anions over cations and weak selectivity among anions, with a selectivity sequence of I > NO3 > Br > Cl > SO4 2 4.8 > 4.4 > 2.2 > 1 > 0.55, which corresponds to Eisenman series 1. The channel is characterized by two open and two closed states, with dominant long open ( o2 35.0 3.9 ms) and long closed ( c2 166 28 ms) states occupying 63% 8% and 79% 3% of total open and closed times, respectively. The ORAC is insensitive to anthracene9-carboxylic acid (<200 M), but 2 mM malate reversibly inhibits 59% 12% of the channel activity. Based on the electrophysiological properties of the channel, we propose that the ORAC plays a role in anion accumulation and in membrane potential regulation through local membrane depolarization.
Clinical Trial Phases

Developers of drugs, biologicals, and medical devices must ensure product safety, demonstrate medical benefit in people, and mass produce the product. Preclinical development starts before clinical trials and the main goals are to determine safety and effectiveness of the intervention. If preclinical studies show that the therapy is safe and effective, clinical trials are started. Clinical trial phases are steps in the research to determine if an intervention would be beneficial or detrimental to humans and include Phases 0, I, II, III, IV, and V clinical studies. Understanding the basis of clinical trial phases will help researchers plan and implement clinical study protocols and, by doing so, improve the number of therapies coming to market for patients.
Humerus Nonunion After Intramedullary Rod Fixation: Locking Compression Plating Without Removing the Nail

Summary The results of operative treatment of humeral nonunion after intramedullary rod fixation have not been as good as treatment for nonunion after nonoperative treatment or plate fixation. This could be in part the result of the shoulder damage that occurs when removing a well-buried anterograde intramedullary fixation device. Our treatment of patients with humerus nonunion after intramedullary fixation has evolved so that we now treat them without removing the rod. The newer locking compression plates provide additional features that facilitate fixation over an intramedullary device.
Staff-Family Relations and Institutional Care Policies

As institutional care providers increasingly recognize the importance of the family, the quality of staff-family relations has become a concern. This study investigated the relationship between selected facility care policies and staff-family relationships. Data secured from staff members and family members in rural nursing homes revealed a relationship between the family role that the care policy prescribed and the degree of staff-family integration. The study concluded that care policies viewing family members as clients will have positive consequences for staff and families and ultimately the residents.
Documento de consenso en el uso de la granulocitoaféresis en pacientes con enfermedad inflamatoria intestinal

La enfermedad inflamatoria intestinal (EII), concepto que engloba básicamente la colitis ulcerosa (CU) y la enfermedad de Crohn (EC), es un trastorno crónico recurrente, cuya fisiopatología no se conoce del todo y en cuya patogenia participan factores genéticos y ambientales. Son diversas las opciones disponibles para su tratamiento, entre ellas principalmente 3 grandes grupos terapéuticos: los salicilatos, los corticoides y los inmunodepresores. En casos graves en que el tratamiento médico se muestre insuficiente y ante la aparición de determinadas complicaciones, asociadas más frecuentemente con la EC, es necesario recurrir al tratamiento quirúrgico. Recientemente ha aparecido una nueva modalidad terapéutica, la granulocitoaféresis (GCAP). Se ha señalado que la acción inmunomoduladora de este procedimiento permitiría controlar algunos casos de EII en que el tratamiento convencional resulta ineficaz. Gracias a la colaboración de especialistas expertos en la materia, se ha elaborado este documento de consenso, con la finalidad de recopilar toda la información disponible en el momento actual sobre la GCAP, para emitir recomendaciones para su uso de acuerdo con el conocimiento disponible hasta la fecha. Este documento no pretende ser normativo, sino un instrumento de ayuda para el médico que atiende a pacientes con esta enfermedad y facilitar de este modo su manejo.
The Aspergillus fumigatuscspA Gene Encoding a Repeat-Rich Cell Wall Protein Is Important for Normal Conidial Cell Wall Architecture and Interaction with Host Cells

ABSTRACT cspA (for cell surface protein A) encodes a repeat-rich glycophosphatidylinositol (GPI)-anchored cell wall protein (CWP) in the pathogenic fungus Aspergillus fumigatus. The number of repeats in cspA varies among isolates, and this trait is used for typing closely related strains of A. fumigatus. We have previously shown that deletion of cspA is associated with rapid conidial germination and reduced adhesion of dormant conidia. Here we show that cspA can be extracted with hydrofluoric acid (HF) from the cell wall, suggesting that it is a GPI-anchored CWP. The cspA-encoded CWP is unmasked during conidial germination and is surface expressed during hyphal growth. Deletion of cspA results in weakening of the conidial cell wall, whereas its overexpression increases conidial resistance to cell wall-degrading enzymes and inhibits conidial germination. Double mutant analysis indicates that cspA functionally interacts with the cell wall protein-encoding genes ECM33 and GEL2. Deletion of cspA together with ECM33 or GEL2 results in strongly reduced conidial adhesion, increased disorganization of the conidial cell wall, and exposure of the underlying layers of chitin and β-glucan. This is correlated with increasing susceptibility of the ΔcspA, ΔECM33, and ΔcspA ΔECM33 mutants to conidial phagocytosis and killing by human macrophages and hyphal damage induced by neutrophils. However, these strains did not exhibit altered virulence in mice with infected lungs. Collectively, these results suggest a role for cspA in maintaining the strength and integrity of the cell wall.