Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibromyalgia Is Associated with Decreased Connectivity Between Pain- and Sensorimotor Brain Areas

Fibromyalgia (FM) is a syndrome characterized by chronic pain without known peripheral causes. Previously, we have reported dysfunctional pain inhibitory mechanisms for FM patients during pain administration. In this study we employed a seed correlation analysis, independent component analysis (ICA), and an analysis of fractional amplitude of low frequency fluctuations (fALFF) to study differences between a cohort of female FM patients and an age- and sex-matched healthy control group during a resting-state condition. FM patients showed decreased connectivity between thalamus and premotor areas, between the right insula and primary sensorimotor areas, and between supramarginal and prefrontal areas. Individual sensitivity to painful pressure was associated with increased connectivity between pain-related regions (e.g., insula and thalamus) and midline regions of the default mode network (including posterior cingulate cortex and medial prefrontal cortex) among patients and controls. However, neither ICA nor fALFF revealed any group differences. Our findings suggest that abnormal connectivity patterns between pain-related regions and the remaining brain during rest reflect an impaired central mechanism of pain modulation in FM. Weaker coupling between pain regions and prefrontal- and sensorimotor areas might indicate a less efficient system level control of pain circuits. Moreover, our results show that multiple, complementary analytical approaches are valuable for obtaining a more comprehensive characterization of deviant resting-state activity. In conclusion, our findings show that FM primarily is associated with decreased connectivity, for example, between several pain-related areas and sensorimotor regions, which could reflect a deficiency in pain regulation.
Reliability of the two-minute walk test in individuals with transtibial amputation.

OBJECTIVE To determine inter- and intrarater reliability of the two-minute walk test (2MWT) in individuals with transtibial amputation. DESIGN Prospective; test-retest method by a pair of trained physical therapists. SETTING Two regional amputee rehabilitation centers in Canada. PARTICIPANTS Thirty-three subjects (23 men, 10 women; mean age +/- standard error, 63.6+/-2.0y) with transtibial amputation; 6 in outpatient rehabilitation, 27 in inpatient rehabilitation. The most common primary diagnoses were peripheral vascular disease (n=15) and diabetes (n=11). INTERVENTIONS Each subject performed a total of four 2MWTs, 1 test for each rater, on 2 consecutive days at approximately the same time of day. Subjects were given at least a 20-minute rest between tests. The order of raters was randomized on the first day and reversed for the next day. The walk tests were performed in the same enclosed corridors with the same starting point for all tests. The subjects were familiar with the test or were given 1 or more practice tests at least 1 day before testing. Subjects were allowed to walk with a mobility aid of their choice. Raters used a digital stopwatch to time the tests and a calibrated wheel with a counter to measure the distance walked in meters. The raters were blinded to each other's scores. MAIN OUTCOME MEASURE Distance walked in 2 minutes (in meters). RESULTS Within-rater reliability was high (intraclass correlation coefficient [ICC],.90-.96). Between rater reliability was also high (ICC.98-.99). Analysis of variance (ANOVA) showed a significant effect for day of test (P<.001) in the inpatient group but no effect for therapist (P=.098) or for interaction of day and therapist (P=.710). Similarly, in the outpatient group, ANOVA showed a significant effect for day (P=.013) but no effect for therapist (P=.259) or interaction of day and therapist (P=.923). CONCLUSION Although the 2MWT showed evidence of inter- and intrarater reliability in individuals with unilateral below-knee amputation, the distance walked in 2 minutes continued to improve over time. This improvement was not solely the result of a training and learning effect.
An unusual presentation of cat-scratch disease

Cat-scratch disease (CSD) is a relatively common entity, particularly in children. The most common sites of involvement are the axillary lymph nodes, followed by cervical, pre-auricular and submandibular lymph nodes. We present a case of cat-scratch disease in which the initial clinical features were indistinguishable from those of acute bacterial tonsillitis with jugulodigastric lymphadenopathy. This previously unreported apparent mode of presentation is discussed with reference to the current understanding of the disease.
Molecular Characterization of the Processing of Arenavirus Envelope Glycoprotein Precursors by Subtilisin Kexin Isozyme-1/Site-1 Protease

ABSTRACT A crucial step in the life cycle of arenaviruses is the biosynthesis of the mature fusion-active viral envelope glycoprotein (GP) that is essential for virus-host cell attachment and entry. The maturation of the arenavirus GP precursor (GPC) critically depends on proteolytic processing by the cellular proprotein convertase (PC) subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P). Here we undertook a molecular characterization of the SKI-1/S1P processing of the GPCs of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and the pathogenic Lassa virus (LASV). Previous studies showed that the GPC of LASV undergoes processing in the endoplasmic reticulum (ER)/cis-Golgi compartment, whereas the LCMV GPC is cleaved in a late Golgi compartment. Herein we confirm these findings and provide evidence that the SKI-1/S1P recognition site RRLL, present in the SKI-1/S1P prodomain and LASV GPC, but not in the LCMV GPC, is crucial for the processing of the LASV GPC in the ER/cis-Golgi compartment. Our structure-function analysis revealed that the cleavage of arenavirus GPCs, but not cellular substrates, critically depends on the autoprocessing of SKI-1/S1P, suggesting differences in the processing of cellular and viral substrates. Deletion mutagenesis showed that the transmembrane and intracellular domains of SKI-1/S1P are dispensable for arenavirus GPC processing. The expression of a soluble form of the protease in SKI-I/S1P-deficient cells resulted in the efficient processing of arenavirus GPCs and rescued productive virus infection. However, exogenous soluble SKI-1/S1P was unable to process LCMV and LASV GPCs displayed at the surface of SKI-I/S1P-deficient cells, indicating that GPC processing occurs in an intracellular compartment. In sum, our study reveals important differences in the SKI-1/S1P processing of viral and cellular substrates.
Operative management of metastatic and malignant primary subaxial cervical tumors.

OBJECT The authors describe the preoperative assessment, intraoperative strategies, and long-term outcomes in 41 consecutive patients who underwent spinal reconstruction after resection of subaxial cervical neoplasms. METHODS Thirty-three tumors were metastatic and eight were primary. Preoperative studies included direct laryngoscopy and vertebral artery (VA) balloon occlusion tests in selected patients. Based on the tumor location, approaches included 12 anterior, 13 posterior, and 16 combined. All patients underwent aggressive intralesional resection and spinal reconstruction. In 12 patients, the VA was dissected from the periphery of the tumor, two cases of which required ligation. Fibula allograft and an anterior rigid plate fixation were most commonly used for anterior reconstruction. Posterior reconstruction was initially performed using lateral mass plates (LMPs) in 13 patients and screw/rod systems in the remaining patients. At follow up, pain level improved to mild or was absent in 39 patients (95%) who had presented with moderate or severe pain. The American Spinal Injury Association (ASIA) Scale scores were stable in 25 patients who presented with ASIA Score E and improved in 14 patients (88%) who presented with ASIA Score B, C, or D. Functional radiculopathy significantly improved in 16 (94%) of 17 patients. Complications occurred in 10 patients (24%) and included three fixation failures requiring revision. Two fixation failures involved cervical LMP screw pullout. The overall mean survival duration was 8.6 months for patients with metastatic tumors and 33.4 months for primary tumors. CONCLUSIONS Surgery for the treatment of subaxial spine neoplasms is effective for relieving pain, encouraging functional nerve root recovery, and preserving spinal cord function with acceptable complication rates.
p15 (INK4B) and E-cadherin CpG island methylation is frequent in Egyptian acute myeloid leukemia.

BACKGROUND Hypermethylation within the promoters of selected genes is an epigenetic pathway that appears to be especially common in all types of human haematopoeitic neoplasms. It is usually associated with inactivation of the involved genes, and can be reversed using demethylating agents. The aim of this study is to evaluate the frequency of p15 and E-cadherin promoter methylation in Egyptian acute myeloid leukemia (AML) patients in an attempt to identify a subset of patients who might be candidates for demethylating agents as a form of targeted therapy either as a primary or as an adjunct to current standard induction and post-remission regimens. MATERIAL AND METHODS In the present work we have studied tumor-associated aberrant p15 and E-cadherin promotor methylation in 59 newly diagnosed acute myeloid leukemia (AML) patients using methylation specific PCR. RESULTS Aberrant p15 promoter methylation was detected in 49% (29/59) of the patients. In 4 of these patients, no DNA could be amplified by the p15 unmethylated reaction showing a complete methylation of both alleles in the examined region. In the remaining 25 cases both methylated and unmethylated DNA could be amplified. Aberrant methylation of E-cadherin was detected in 63% (37/59) of the cases. In all of these cases both the methylated and the unmethylated alleles were amplified denoting partial methylation of the examined region. Concomitant methylation of p15 and E-cadherin was detected in 40% (23/59) of all the cases tested, while in 27% (16/59) of the cases both genes were not methylated. CONCLUSION These results demonstrate that p15 and E-cadherin promoter methylation are frequent events in Egyptian AML and provide an impetus for larger studies to define the extent and pattern of methylation in the various subgroups of AML. Methylation studies, therefore, represent a novel additional tool to define the subset of patients who might benefit from demethylating agents,thus providing the molecular basis for targeted therapeutic approaches and better designing of risk-adapted therapy.
Genetics of Diabetic Retinopathy

Abstract Multiple studies have shown that genetic factors may play an important role in determining an individual’s risk for the development of diabetic retinopathy (DR) and progression to proliferative DR. However, consistent and definitive genetic associations with DR across broad populations have been not been established. Numerous genes have been studied for their association with DR and the results of these investigations have most specifically pointed to three specific genes that are likely involved in DR development and progression. The gene coding for vascular endothelial growth factor, aldose reductase, and the receptor for advanced glycation end products have been extensively evaluated, and specific polymorphisms of these genes have been suggested to potentially increase the risk of DR development. In this paper, we have reviewed the published literature on the genetics of DR and the potential implications for DR development and progression.
Kinematic calibration of an active camera system

A technique for the calibration of an active camera system is presented. The calibration of manipulator, camera-to-manipulator, camera, and base-to-world is treated in a unified and elegant way. In this approach, the camera frames and manipulator link frames are all related to the world frame, therefore the camera-to-manipulator and base-to-world calibration is very straightforward. The approach is simple, since it uses the form of one equation solving one parameter. Two experiments that verify the accuracy of the technique are reported. <<ETX>>
In the Multi-domain Protein Adenylate Kinase, Domain Insertion Facilitates Cooperative Folding while Accommodating Function at Domain Interfaces

Having multiple domains in proteins can lead to partial folding and increased aggregation. Folding cooperativity, the all or nothing folding of a protein, can reduce this aggregation propensity. In agreement with bulk experiments, a coarse-grained structure-based model of the three-domain protein, E. coli Adenylate kinase (AKE), folds cooperatively. Domain interfaces have previously been implicated in the cooperative folding of multi-domain proteins. To understand their role in AKE folding, we computationally create mutants with deleted inter-domain interfaces and simulate their folding. We find that inter-domain interfaces play a minor role in the folding cooperativity of AKE. On further analysis, we find that unlike other multi-domain proteins whose folding has been studied, the domains of AKE are not singly-linked. Two of its domains have two linkers to the third one, i.e., they are inserted into the third one. We use circular permutation to modify AKE chain-connectivity and convert inserted-domains into singly-linked domains. We find that domain insertion in AKE achieves the following: (1) It facilitates folding cooperativity even when domains have different stabilities. Insertion constrains the N- and C-termini of inserted domains and stabilizes their folded states. Therefore, domains that perform conformational transitions can be smaller with fewer stabilizing interactions. (2) Inter-domain interactions are not needed to promote folding cooperativity and can be tuned for function. In AKE, these interactions help promote conformational dynamics limited catalysis. Finally, using structural bioinformatics, we suggest that domain insertion may also facilitate the cooperative folding of other multi-domain proteins.
Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease.

OBJECTIVE To retrospectively evaluate the efficacy and safety of rituximab (Rtx) treatment in patients with anti-synthetase syndrome (ASS) and severe interstitial lung disease (ILD). METHODS Patients with severe ILD and >12 months follow-up post-Rtx were identified from the Oslo University Hospital ASS cohort (n = 112). Clinical data, including pulmonary function tests (PFTs), were retrospectively collected from medical reports. Extent of ILD pre-, and post-Rtx was scored on thin-section high-resolution CT (HRCT) images and expressed as a percentage of total lung volume. Muscle strength was evaluated by manual muscle testing of eight muscle groups (MMT8). RESULTS Altogether, 34/112 ASS patients had received Rtx; 24/34 had severe ILD and >12 months follow-up post-Rtx (median 52 months). In these 24 patients, the median percentage of predicted forced vital capacity, forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lungs for carbon monoxide (DLCO) increased by 24%, 22% and 17%, respectively, post-Rtx. Seven patients (all with disease duration <12 months and/or acute onset/exacerbation of ILD) had >30% improvement in all three PFTs. HRCT analysis showed a median 34% reduction in ILD extent post-Rtx. MMT8 score increased post-Rtx. During follow-up, 7/34 (21%) Rtx-treated ASS patients died; 6/7 deaths were related to infections. The mortality rate in the Rtx-treated group was comparable to that of the remaining ASS cohort (25/78 deceased; 32%). CONCLUSION This study, which included 24 Rtx-treated ASS patients with severe ILD, reports improved PFTs after a median 52 months follow-up post-Rtx. The best outcome was observed in patients with a disease duration <12 months and/or acute onset/exacerbation of ILD. The study indicates that Rtx could be a treatment option for selected ASS patients, but infections should be given attention.
Radiological findings and their clinical correlations in nephropathia epidemica

Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome (HFRS). Its course varies from asymptomatic to fatal. The etiologic agent, Puumala virus, belongs to the Hantavirus genus of the Bunyaviridae family. Respiratory symptoms, from common cold to respiratory distress, occur in NE. Acute renal failure (ARF) is evident in over 90% of hospital-treated NE patients. In this review article, special attention is paid to radiological lung and renal involvement to investigate the occurrence and type of manifestations during the acute phase of infection and recovery.
USPIO-enhanced direct MR imaging of thrombus: preclinical evaluation in rabbits.

PURPOSE To test the hypothesis that ultrasmall superparamagnetic iron oxide (USPIO) particles may diffuse into nonendothelialized fresh thrombi and thus allow for direct magnetic resonance (MR) imaging of a thrombus. MATERIALS AND METHODS Stagnation thrombi of different thrombus ages (1, 3, 5, 7, and 9 days) were induced in the external jugular veins of 25 rabbits. Direct MR imaging of thrombi was performed by using a fat-saturated T1-weighted gradient-echo sequence (three-dimensional [3D] magnetization prepared rapid acquisition gradient echo) before and 24 hours after intravenous administration of USPIO (particle size, 25 nm; 200 micromol per kilogram of body weight). Thrombus length on 3D reconstruction images was compared with that depicted on a radiographic venogram and with histologic findings (joint reference standard). In addition, T2*-weighted gradient-echo images were acquired and scored semiquantitatively. RESULTS The hyperintensity of the thrombus segment depicted on T1-weighted images (thrombus length determined with 3D reconstruction images divided by true thrombus length) increased significantly after administration of contrast medium at a thrombus age of 3 days (0.6 +/- 0.4 [SD] to 0.8 +/- 0.4; P =.02), 5 days (0.1 +/- 0.1 to 1.0 +/- 0.1; P <.001), and 7 days (0 to 0.6 +/- 0.4; P =.02), but not at an age of 1 and 9 days. No significant change in the thrombus signal intensity was observed on T2*-weighted images. CONCLUSION The animal model showed that direct MR imaging of the thrombus improved 24 hours after USPIO administration with a T1-weighted sequence. No improvement was seen with the T2*-weighted sequence.
Counselor Training as a Treatment for Alcoholism: the Helper Therapy Principle in Action

Extensive harmful drinking of alcohol is a major problem for many groups of Australian Aborigines and western treatment approaches have had limited effect. In order to stress cultural factors in treatment, a program to train indigenous Aborigines as alcoholism counselors for their communities was developed. In its more than 10 years of existence 145 counselors have been graduated. Of those initially entering the two year program 60% have graduated. Most of those have found employment as alcohol counselors for their people, and the numbers of Aborigines treated has increased. About 90% of those who entered the training had severe repeated substance abuse disorders in their recent history. The training and the alcohol counseling employment appears to be highly associated with continuing sobriety. For those who graduated the program only 4.8% returned to drinking. Those who completed only the first phase, 8.4% returned to drinking. Of those who were terminated from the program, 74% returned to drinking. Training alcoholics as alcohol counselors appears to be associated with vocational success and mainte nance of sobriety as predicted by Riessman's "helper-therapy principle. "
Neurotrophin receptors: Old friends with new partners

Neurotrophins are important regulators of embryonic development and adult function of most populations of neurons in vertebrate nervous systems. This signaling system regulates many diverse activities, including survival, axon outgrowth, and synaptic plasticity. In mammals, neurotrophin action is mediated by four receptors, p75NTR, TrkA, TrkB, and TrkC. Although early studies viewed these receptors as solitary agents in the cells outer membrane, recent discoveries reveal that the cell outer membrane is a crowded and highly interactive neighborhood. Neurotrophin receptors partner with a diverse array of membrane proteins, dramatically expanding their functional repertoire. This review will focus on some of the most recent discoveries concerning the promiscuous partnering of neurotrophin receptors. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 2010
A Compiler that Increases the Fault Tolerance of Asynchronous Protocols

A compiler that increases the fault tolerance of certain asynchronous protocols is presented. Specifically, it transforms a source protocol that is resilient to crash faults into an object protocol that is resilient to Byzantine faults. The compiler simplifies the design of protocols for the Byzantine fault model because it allows the design process to be broken in two steps. The first step is to design a protocol for the crash fault model. The second step, which is completely mechanical, is to compile the protocol into one for the Byzantine fault model. The compiler is used to produce an asynchronous approximate agreement protocol that operates in the Byzantine fault model and improves in several respects on the performance of the asynchronous approximate agreement protocol of D. Dolev et al. (1986). >
NPY/sympathetic and NPY/VIP innervation of the blood vessels supplying rat tooth-related structures: effects of sympathectomy

In order to better understand the regulation of blood flow to tooth-related structures, the patterns of VIP- and NPY-ergic innervations in the rat were examined. Nerve fibers showing NPY-like immunoreactivity (NPY-LI) frequently occurred in the walls of the large main arteries, as well as in association with the arterioles, to a high degree co-existing with tyrosine hydroxylase (TH), whereas VIP-LI was mainly restricted to the walls of the large arteries. After sympathectomy, no NPY/TH-LI nerve fibers were seen in blood vessel walls. However, a NPY-immunoreactive nerve population remained in the walls of the large arteries, NPY- and VIP-LI co-existing in this nerve population. Both immunoreactions were intense. The present study suggests that a NPY/sympathetic innervation as well as a VIP innervation (large arteries) are likely to have substantial roles in the balance and maintenance of vasoregulation in tooth-related structures and that a NPY/VIP innervation becomes of particular importance when the NPY/sympathetic innervation is destroyed.
Variation in Developmental Time for Geographically Distinct Populations of the Common Green Bottle Fly, Lucilia sericata (Meigen) *

Abstract: Time between death and discovery of remains, or postmortem interval (PMI), can be assessed using blow fly maggot age. Forensic entomologists rely on published, often nonlocal, species‐specific developmental tables to determine maggot age. In a series of common garden experiments, we investigated the developmental rate variation between populations of Lucilia sericata collected from Sacramento, CA, San Diego, CA, and Easton, MA at 16°C, 26°C, and 36°C. For the 16°C trial the time measurement started at egg hatch, while for the higher temperatures the experiment began at oviposition; the wandering stage signified the endpoint for all experiments. The distribution of developmental times differed significantly (ANOVA, p < 0.001) between the three populations within each temperature treatment. We discovered that regional variation of developmental times within a blow fly species exists. This study demonstrates the importance of assembling local population‐specific developmental tables when estimating larval age to determine PMI.