Miracle-dz/UniFAR-FTUs huggingface dataset:
Clozapine-induced agranulocytosis. Incidence and risk factors in the United States.

BACKGROUND Clozapine is an atypical antipsychotic agent that is more effective than standard neuroleptic drugs in the treatment of patients with refractory schizophrenia. Unlike classic neuroleptic agents, clozapine is not associated with the development of acute extrapyramidal symptoms or tardive dyskinesia. The main factor limiting its use is the risk of potentially fatal agranulocytosis, estimated to occur in 1 to 2 percent of treated patients. After clozapine was approved by the Food and Drug Administration, it became available for marketing in the United States in February 1990 only as part of a special surveillance system (the Clozaril Patient Management System, or CPMS), in which a weekly white-cell count was required for the patient to receive a supply of the drug. METHODS We evaluated the CPMS data for February 1990 through April 1991 by survival analysis to determine the incidence of agranulocytosis and the effects of potential risk factors such as age and sex. Data were available for 11,555 patients who received clozapine during the period after marketing began. RESULTS Agranulocytosis developed in 73 patients, resulting in death from infectious complications in 2 patients. Episodes of agranulocytosis occurred in 61 patients within three months after they began treatment. The cumulative incidence of this side effect was 0.80 percent (95 percent confidence interval, 0.61 to 0.99) at 1 year and 0.91 percent (95 percent confidence interval, 0.62 to 1.20) at 1 1/2 years. The risk of agranulocytosis increased with age and was higher among women. CONCLUSIONS The occurrence of agranulocytosis is a substantial hazard of the administration of clozapine, but this hazard can be reduced by monitoring the white-cell count. The increasing risk of agranulocytosis with age and the reduced incidence after the first six months of treatment provide additional guidelines for the prescription and monitoring of clozapine treatment in the future.
The Soul’s Legacy: A Program Designed to Help Prepare Senior Adults Cope With End-of-Life Existential Distress

Current innovative psychological therapies have made great progress in addressing existential suffering in dying patients but are often begun to late in the end-of-life process and often ignore religion, which for many is a major component in the meaning-making process. Therefore, this article explores how chaplains (who are familiar with various religious traditions without promoting them) can help prepare senior adults effectively cope with inevitable end-of-life existential issues. The project described in this article provides tools for chaplains to address the real issues that terrify us all, but particularly the elderly: death, isolation, and meaninglessness. It is proposed that the addition of a spiritual will or legacy of the soul added to end-of-life planning can help ameliorate existential suffering at life’s end.
Long-term evidence for favorable midfacial growth after delayed hard palate repair in UCLP patients.

OBJECTIVE To investigate whether delayed hard palate repair resulted in better midfacial growth in the long term than previously achieved with "conventional" surgical methods of palatal closure. DESIGN AND SETTING Long-term cephalometric data from patients with unilateral cleft lip and palate were available from two Scandinavian cleft centers. The patients had been treated by different regimens, particularly regarding the method and timing of palatal surgery. Patients were analyzed retrospectively, and one investigator digitized all radiographs. PATIENTS Thirty consecutively treated subjects from each center, with cephalograms taken at three comparable stages between 10 and 16 years of age. RESULTS AND CONCLUSIONS Patients whose hard palates were repaired late (early soft palate closure followed by delayed hard palate repair at the stage of mixed dentition) had significantly better midfacial development than patients in whom the hard palate was operated on early with a vomer flap, and then during the second year of life, the soft palate was repaired with a push-back procedure. As the growth advantage in the delayed hard palate repair group was accomplished without impeding long-term speech development, the delayed repair regimen proved to be a good alternative in surgical treatment of patients with unilateral cleft lip and palate.
Adaptive traffic measurement for MBAC system

Quality of service guarantees have attracted a lot of research interest in the past decade as real-time applications are sensitive both to delay and loss. Dynamic management of system parameters like bandwidth and buffer capacity allows to gain essential performance benefits while quality of service guarantees are met. Recently, a method of admission control based on measurements (MBAC) have received a wide recognition. The present paper shows several solutions to minimize possible errors of flows parameters estimation which is critical for making the correct decision about a new flow allowance.
Comments on "Plane-Based Optimization for 3D Object Reconstruction from Single Line Drawings"

I comment on a paper describing a method for inflating a 2D wireframe topological representation of an object to 3D. There are several problems with this paper and the method it describes. An oversimplified problem statement and concentration on mathematical ingenuity rather than comprehension lead the authors to develop a method which is not well-suited to the problem. Failure to take proper account of previous work leads them to compare their method, not with the true state of the art, but with older, less successful approaches. Finally, they omit entirely any mention of, let alone a proposed solution to, the most intractable problem in the area, that of finding resolution sequences.
[The key components and method of designing syndromic surveillance].

近十年来,症状监测作为一种新兴的公共卫生监测手段引起了普遍的关注. 相对于基于病例诊断的传统公共卫生监测手段,症状监测是对临床诊断前患者相关的非特异性信息进行监测[1]. 相关研究表明,症状监测可应用于公共危机应对(如生物恐怖事件早期发现[2,3]、自然灾害传染病应急监测[4]),早期探测新发传染病[5],掌握疾病发病水平与流行趋势(如急性迟缓性麻痹综合征监测和流感样病例监测[6,7]),以及大型体育活动与政治集会等大规模人群聚集活动公共卫生保障[8,9]。
Posthospital care transitions: patterns, complications, and risk identification.

OBJECTIVES To (1) describe patterns of posthospital care transitions; (2) characterize these patterns as uncomplicated or complicated; (3) identify those at greatest risk for complicated transitions. DATA SOURCES/STUDY SETTING The Medicare Current Beneficiary Survey was used to identify beneficiaries aged 65 and older who were discharged from an acute care hospital in 1997-1998. STUDY DESIGN Patterns of posthospital transfers were described over a 30-day time period following initial hospital discharge. Uncomplicated posthospital care patterns were defined as a sequence of transfers from higher-to lower-intensity care environments without recidivism, while complicated posthospital care patterns were defined as the opposite sequence of events. Indices were developed to identify patients at risk for complicated transitions. PRINCIPAL FINDINGS Forty-six distinct types of care patterns were observed during the 30 days following hospital discharge. Among these patterns, 444 episodes (61.2 percent) were limited to a single transfer, 130 episodes (17.9 percent) included two transfers, 62 episodes (8.5 percent) involved three transfers, and 31 episodes (4.3 percent) involved four or more transfers. Fifty-nine episodes (8.1 percent) resulted in death. Between 13.4 percent and 25.0 percent of posthospital care patterns in the 1998 sample were classified as complicated. The area under the receiver operating curve was 0.771 for a predictive index that utilized administrative data and 0.833 for an index that used a combination of administrative and self-reported data. CONCLUSIONS Posthospital care transitions are common among Medicare beneficiaries and patterns of care vary greatly. A significant number of beneficiaries experienced complicated care transitions-a finding that has important implications for both patient safety and cost-containment efforts. Patients at risk for complicated care patterns can be identified using data available at the time of hospital discharge.
Long bone articular and diaphyseal structure in Old World monkeys and apes. II: Estimation of body mass.

Body mass estimation equations are generated from long bone cross-sectional diaphyseal and articular surface dimensions in 176 individuals and 12 species of hominoids and cercopithecoids. A series of comparisons is carried out to determine the best body mass predictors for each of several taxonomic/locomotor groupings. Articular breadths are better predictors than articular surface areas, while cross-sectional shaft strengths are better predictors than shaft external breadths. Percent standard errors of estimate (%SEEs) and percent prediction errors for most of the better predictors range between 10-20%. Confidence intervals of equations using sex/species means are fairly representative of those calculated using individual data, except for sex/species means equations with very low %SEEs (under about 10%), where confidence intervals (CIs) based on individuals are likely to be larger. Given individual variability, or biological "error," this may represent a lower limit of precision in estimating individual body masses. In general, it is much more preferable to determine at least broad locomotor affinities, and thus appropriate modern reference groups, before applying body mass estimation equations. However, some structural dimensions are less sensitive to locomotor distinctions than others; for example, proximal tibial articular M-L breadth is apparently "locomotor blind" regarding body mass estimation within the present study sample. In other cases where locomotor affiliation is uncertain, mean estimates from different reference groups can be used, while for some dimensions no estimation should be attempted. The techniques are illustrated by estimating the body masses of four fossil anthropoid specimens of Proconsul nyanzae, Proconsul heseloni, Morotopithecus bishopi, and Theropithecus oswaldi.
Primary mediastinal large B-cell lymphoma: Clinical features, prognostic factors and survival with RCHOP in Arab patients in the PET scan era

Objective: PMBCL is a distinct type of nonhodgkins lymphoma with specific clinicopathological features. To clarify clinical features, treatment alternatives and outcomes, we evaluated 28 Arab patients treated with chemotherapy or radiotherapy between 2006 and 2011. Patients and Methods: PMBCL lymphoma patients identified according to WHO classification and treated at KCCC between 2006 and 2011 were included in this study. Demographic and clinical data are presented as means or medians. Overall survival was estimated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. A P < 0.05 was considered significant. Results: The median age of the patients was 31 years and the male to female ratio was 2:1. Majority of the patients (75%) presented with stage I/II disease. Most had features of local extension like pleural effusion (18%) and SVCO (39%). Only 11% of the patients had bone marrow involvement at presentation. 96% of the patients required biopsy from the mediastinal mass either by image guided core biopsy (75%) or by surgical biopsy. Most patients were treated by RCHOP and involved field radiotherapy. Patients with positive PET scan after RCHOP chemotherapy received salvage chemotherapy and BEAM autologous marrow transplant. The five year OS for the entire group was 85% while the PFS was 73%. Patients who had PET scan for response evaluation had better OS [P = 0.013] and PFS [P = 0.039] when compared with those patients who received only radiotherapy based on CT scan evaluation. Conclusion: PMBCL is a specific lymphoma entity seen in the young with good survival. The role of PET scan for response evaluation and the type of consolidation therapy needs to be further clarified
Decoding the Role of Glycans in Malaria

Complications arising from malaria are a concern for public health authorities worldwide, since the annual caseload in humans usually exceeds millions. Of more than 160 species of Plasmodium, only 4 infect humans, with the most severe cases ascribed to Plasmodium falciparum and the most prevalent to Plasmodium vivax. Over the past 70 years, since World War II, when the first antimalarial drugs were widely used, many efforts have been made to combat this disease, including vectorial control, new drug discoveries and genetic and molecular approaches. Molecular approaches, such as glycobiology, may lead to new therapeutic targets (both in the host and the parasites), since all interactions are mediated by carbohydrates or glycan moieties decorating both cellular surfaces from parasite and host cells. In this review, we address the carbohydrate-mediated glycobiology that directly affects Plasmodium survival or host resistance.
Regulation of glomerular filtration in essential hypertension: role of abnormal Na+ transport and atrial natriuretic peptide.

BACKGROUND Many studies conducted in the last two decades have aroused interest in the role of glomerular hyperfiltration in the pathogenesis of renal damage in hypertension. Glomerular hyperfiltration has been mainly attributed to intraglomerular hypertension and overactivity of the renin-angiotensin system, but not much is known about the role of excessive renal proximal tubule Na+ reabsorption, which may activate tubuloglomerular feedback and increase glomerular filtration. Therefore, we evaluated the relationships between glomerular hemodynamics, plasma atrial natriuretic peptide (ANP) concentration, proximal tubule Na+ reabsorption, assessed by renal Li+ reabsorption, and sodium-lithium exchange (NLE) in circulating erythrocytes ex vivo, a marker of increased protein expression of isoform 3 of the sodium-proton exchanger (NHE-3) in the proximal tubule, in essential hypertensive patients. METHODS 32 patients with essential hypertension were investigated after a two week placebo wash out period and after four-weeks treatment with open-label angiotensin converting enzyme inhibitors (ACEI). Before and after active treatment the following parameters were assessed: blood pressure (mercury sphygmomanometry), glomerular filtration rate (GFR), renal plasma flow, and lithium clearance (clearances of inulin, PAH and orally administered lithium, respectively), plasma ANP (radioimmunoassay), and, only at baseline, plasma renin activity, plasma and urinary aldosterone (radioimmunoassay) and NLE (sodium stimulated lithium efflux). RESULTS Baseline GFR was positively correlated with NLE, Li+ clearance and ANP, and the patients with elevated NLE (> or =0.4 mmol/L cell/h) (31%) had higher GFR and ANP than the patients with normal NLE, but similar plasma renin activity, plasma and urinary aldosterone. ACEI reduced GFR and its change was negatively correlated with pretreatment GFR and NLE and positively with the change of proximal tubule Na+ reabsorption. After ACEI, ANP increased in patients with normal NLE but not in those with high NLE (p<0.001 for the difference). CONCLUSION Increased proximal tubule Na+ reabsorption contributes to the pathophysiology of glomerular hyperfiltration in patients with essential hypertension, and is compensated by increased ANP levels. It can be corrected by short-term ACEI treatment.
A multiscale approach to predicting affinity changes in protein–protein interfaces

Substitution mutations in protein–protein interfaces can have a substantial effect on binding, which has consequences in basic and applied biomedical research. Experimental expression, purification, and affinity determination of protein complexes is an expensive and time‐consuming means of evaluating the effect of mutations, making a fast and accurate in silico method highly desirable. When the structure of the wild‐type complex is known, it is possible to economically evaluate the effect of point mutations with knowledge based potentials, which do not model backbone flexibility, but these have been validated only for single mutants. Substitution mutations tend to induce local conformational rearrangements only. Accordingly, ZEMu (Zone Equilibration of Mutants) flexibilizes only a small region around the site of mutation, then computes its dynamics under a physics‐based force field. We validate with 1254 experimental mutants (with 1–15 simultaneous substitutions) in a wide variety of different protein environments (65 protein complexes), and obtain a significant improvement in the accuracy of predicted ΔΔG. Proteins 2014; 82:2681–2690. © 2014 Wiley Periodicals, Inc.
Cross-Layer Performance of Downlink Dynamic Cell Selection With Random Packet Scheduling and Partial CQI Feedback in Wireless Networks With Cell Sleeping

In this paper, we consider a coordinated multipoint dynamic cell selection (DCS) transmission scheme for serving sleeping cell user equipments (UEs). According to this DCS scheme, packets of UEs in a sleeping cell are randomly forwarded to the potential active base stations (BSs) by the packet serving gateway and UEs in the sleeping cell dynamically select their serving BS from these active BSs. We model the system as a fork/join (F/J) queuing system and develop a cross-layer analytical model that considers the time varying nature of the channels, channel scheduling mechanism, partial channel quality information feedback, cell selection mechanism, bursty packet arrivals, and packet scheduling mechanism. The developed analytical model can be used to measure various packet-level performance parameters, such as packet loss probability (PLP) and queuing delay while accounting for out-of-sequence packet delivery. We validate the accuracy of the developed analytical model via simulations, and we compare the performance of the DCS scheme under consideration with the conventional fixed cell selection scheme and with the state-of-the-art DCS scheme. Presented numerical results show that the DCS scheme under consideration significantly improves the PLP performance. Queuing delay performance, on the other hand, depends on the system and operating parameters.
Plasminogen activation in degradation and penetration of extracellular matrices and basement membranes by invasive bacteria.

Methods to assess in vitro the role of plasminogen activation in enterobacterial degradation of extracellular matrices and their protein components as well as in penetration through basement membrane are described. Development of these methods was initiated after the findings that enterobacterial surface structures (fimbriae and the Pla surface protease) function in plasminogen activation as well as in laminin- and/or fibronectin-specific adhesion. Enterobacteria with these properties degrade radiolabeled laminin as well as metabolically labeled extracellular matrix from cultured endothelial or epithelial cells. Plasmin-coated bacteria also penetrate through the reconstituted basement membrane preparation Matrigel. The processes are dependent on plasminogen activation by the invasive bacteria. The results suggest a pathogenic similarity between enterobacteria and tumor cells in cellular metastasis through tissue barriers.
Identification and characterization of the human protein kinase-like gene NTKL: mitosis-specific centrosomal localization of an alternatively spliced isoform.

Although the centrosome has an essential role in mitosis, its molecular components have not been fully elucidated. Here, we describe the molecular cloning and characterization of the human gene NTKL, which encodes an evolutionarily conserved kinase-like protein. NTKL mRNA is found ubiquitously in human tissues. NTKL is located on 11q13 and is mapped around chromosomal breakpoints found in several carcinomas, suggesting that NTKL dysfunction may be involved in carcinogenesis. Alternative splicing generates two variant forms of NTKL mRNA that encode protein isoforms with internal deletions. When fused to green fluorescent protein, the full-length product and one of the variant proteins are found in cytoplasm. The other variant product also exists in the cytoplasm during interphase, but is found in the centrosomes during mitosis. Endogenous NTKL protein is also localized to the centrosomes during mitosis. This cell-cycle-dependent centrosomal localization suggests that NTKL is involved in centrosome-related cellular functions.
Impaired Washout – Embolism and Ischemic Stroke: Further Examples and Proof of Concept

We previously posited that impaired washout of emboli was an important mechanism of brain infarction in patients with cerebral hypoperfusion. Hyperviscosity and hypoperfusion enhance thrombus formation promoting embolization of fresh thrombi. Hypoperfusion also reduces dissolution of emboli due to reduced flow velocity leading to classic hemodynamic patterns of stroke. To prove this concept further, we identified patients with severe hemodynamic compromise of either arterial or venous origin, or both, and natural or iatrogenic mechanisms of embolism. Three conditions were investigated in a stroke MRI protocol: 5 patients who had conventional cerebral angiography for the diagnosis of moyamoya disease, 1 patient with atrial fibrillation and thrombosis of the left transverse dural sinus and 1 patient with a patent foramen ovale with atrial septum aneurysm presenting with thrombosis of cortical cerebral veins. In all patients, subcortical arterial embolization within an atypical borderzone of hypoperfusion was observed.
Continuity and change from early childhood to adolescence in autism.

BACKGROUND This longitudinal study of 48 children diagnosed with autism at 2-5 years of age was designed to test the hypothesis that diagnosis would remain stable for most of the sample but that there would be improvements in symptom severity, adaptive behavior, and emotional responsiveness in adolescence. METHODS A sample of children with autism assessed in both early and middle childhood were observed in late adolescence with the Autism Diagnostic Observation Scale (ADOS) and their parents were administered the Autism Diagnostic Interview-Revised (ADI-R) and the Vineland Adaptive Behavior Scale. RESULTS All but 2 adolescents (46 of 48) met lifetime criteria for autism according to the ADI-R, and all but 4 adolescents (40 of 44) met criteria for autism spectrum disorder on the ADOS. In contrast to the continuity in diagnosis, parents described improvements in social interactions, repetitive/stereotyped behaviors, adaptive behaviors, and emotional responsiveness to others' distress in adolescence compared to middle childhood. High-functioning adolescents with autism showed more improvement in these domains than low-functioning adolescents with autism. The extent to which the adolescents were observed to be socially engaged with their peers in school in middle childhood predicted adaptive behavior skills even when intelligence level was statistically constrained. CONCLUSIONS The developmental trajectory of children with autism appears to show both continuity and change. In this sample, most individuals continued to be diagnosed in the autism spectrum but parents reported improvements in adolescence. The results suggest that social involvement with peers improves adaptive behavior skills, and this argues for focusing intervention programs in this area. In addition, it is clear that high-functioning adolescents improve more than low-functioning individuals not only in cognitive abilities but also in social interaction skills. Thus, any early intervention that impacts the cognitive abilities of young children with autism is likely to have a parallel influence on their social skills as they mature into late adolescence and early adulthood.