Miracle-dz/UniFAR-FTUs huggingface dataset:
The application of control limits analysis to the myometric assessment of motor performance in neuropathy patients

Measurement of muscle strength by myometry is used to monitor the natural course and treatment response of motor system diseases, both in individual patients and clinical trials. However, the practical usefulness of myometric data is reliant upon a statistical method for analysing serial strength measurements which distinguishes disease‐related changes from random fluctuations in patient performance and operator/device dependent measurement errors. In this study we have applied control limits analysis to this problem. Using hand‐held dynamometry, sets of baseline strength measurements were collected on two separate occasions during a period of clinical stability from up to four muscle groups in 22 patients with peripheral neuropathies. From these sets of data, 76 control limits were calculated and then used to describe the inter‐measurement variation in muscle strength in individual muscles. The range of control limits was wide, varying from <10% of baseline (in 36% of muscles tested) to >50% (in 4% of muscles tested), with 88% of muscles falling within 30% of baseline. Follow‐up data were also collected from all patients, including those undergoing treatment. Control limits analysis is a powerful and simple method for assessing the significance of motor performance changes in individual muscles in patients undergoing serial monitoring and can be easily applied to both single patients and clinical trials.
Use of the Wii Fit system for the treatment of balance problems in the elderly: A feasibility study

This paper is a report of the feasibility and outcome of using a low-cost, commercially available gaming system - Wii Fit - for balance training after stroke. The patient was an 86 year-old woman five weeks after stroke, who was unable to walk without close supervision, even with a walker, due to poor balance and a tendency to fall. In addition to standard physical therapy, the patient participated in four training sessions with the Wii Fit system; each training session included four different games. The outcome measures were Berg Balance Scale (BBS), the Functional Reach and Lateral Reach tests, Timed Up & Go test (TUG), computerized posturography, and the Short Feedback Questionnaire (SFQ). The tests were done before the intervention and on the last day of training. The SFQ was done during the third training session. The patient greatly enjoyed the training sessions and felt that she was receiving very ‘up-to-date’ treatment. She did not experience any discomfort such as nausea or dizziness while using the system. Following combined Wii and standard treatment, the patient demonstrated improved antero-posterior symmetry of stance, and there was a 10 second improvement in her TUG score. When released from hospital, she was able to walk with a walker with minimal supervision. This initial pilot study indicates that the Wii Fit gaming system has the potential to be used in clinical settings in order to improve balance. A full clinical trial is necessary in order to examine this premise.
Bathing disability and the risk of long-term admission to a nursing home.

BACKGROUND The prevalence of disability in bathing and the likelihood of a long-term nursing home admission increase substantially with age. We performed a prospective study to determine whether the occurrence of persistent disability in bathing is associated with the risk of a long-term nursing home admission, independent of potential confounders, including persistent disability in other essential activities of daily living. METHODS We studied 754 community-living persons, 70 years old or older, who were nondisabled in four essential activities of daily living. Participants were followed with monthly telephone interviews for a median of 75 months to determine the occurrence of persistent (i.e., present for at least 2 consecutive months) disability in bathing and the time to the first long-term nursing home admission, defined as longer than 3 months. RESULTS One hundred thirteen (15.0%) participants had a long-term nursing home admission. At least one episode of persistent bathing disability occurred among 59 (52.2%) participants with a long-term nursing home admission and 210 (32.8%) without a long-term admission (p <.001). In a proportional hazards model that was fully adjusted for potential confounders, the occurrence of persistent bathing disability increased the risk of a long-term nursing home admission by 77% (hazard ratio 1.77, 95% confidence interval 1.05 to 2.98), but had no effect on the risk of a short-term nursing home admission (hazard ratio 0.87, 95% confidence interval 0.51 to 1.49). CONCLUSIONS Among community-living older persons, the occurrence of persistent disability in bathing is independently associated with the risk of a long-term nursing home admission, but has no effect on short-term admissions. Interventions directed at the prevention and remediation of bathing disability have the potential to reduce the burden and expense of long-term care services.
Intratumoral oxygen gradients mediate sarcoma cell invasion

Significance Previous works demonstrated the role of hypoxia in tumor development and metastasis. However, the understanding how oxygen (O2) gradients regulate early stages of tumor metastasis is lacking. Leveraging our O2-controlling hydrogel, we generated a 3D in vitro model that enables us to analyze cancer cell responses to O2 gradients and small-molecule inhibitors. Using this approach, we present a previously unidentified concept in which O2 acts as a 3D physicotactic agent during sarcoma tumor invasion, findings that are important for the understanding of the metastatic process. Through this concept, we also establish the 3D in vitro model as a platform for testing therapeutic targets and interventions for the treatment of sarcoma and potentially other cancers. Hypoxia is a critical factor in the progression and metastasis of many cancers, including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular supply, leading to heterogeneous areas of O2 depletion. Here, we report the impact of hypoxic O2 gradients on sarcoma cell invasion and migration. O2 gradient measurements showed that large sarcoma mouse tumors (>300 mm3) contain a severely hypoxic core [≤0.1% partial pressure of O2 (pO2)] whereas smaller tumors possessed hypoxic gradients throughout the tumor mass (0.1–6% pO2). To analyze tumor invasion, we used O2-controllable hydrogels to recreate the physiopathological O2 levels in vitro. Small tumor grafts encapsulated in the hydrogels revealed increased invasion that was both faster and extended over a longer distance in the hypoxic hydrogels compared with nonhypoxic hydrogels. To model the effect of the O2 gradient accurately, we examined individual sarcoma cells embedded in the O2-controllable hydrogel. We observed that hypoxic gradients guide sarcoma cell motility and matrix remodeling through hypoxia-inducible factor-1α (HIF-1α) activation. We further found that in the hypoxic gradient, individual cells migrate more quickly, across longer distances, and in the direction of increasing O2 tension. Treatment with minoxidil, an inhibitor of hypoxia-induced sarcoma metastasis, abrogated cell migration and matrix remodeling in the hypoxic gradient. Overall, we show that O2 acts as a 3D physicotactic agent during sarcoma tumor invasion and propose the O2-controllable hydrogels as a predictive system to study early stages of the metastatic process and therapeutic targets.
Altered neural function during episodic memory encoding and retrieval in major depression

Memory impairments are common in major depression. Neural processing during non‐emotional episodic memory in depressed patients has only sparsely been investigated, since the majority of studies have focused on emotional stimuli. The aim of this study was to explore neural correlates of episodic memory in depressive patients and to assess brain regions related to subsequent memory performance. Forty‐six participants (23 depressed patients) performed a non‐emotional episodic memory encoding and retrieval task while brain activation was measured with functional magnetic resonance imaging. Patients with depression showed decreased activation in the right prefrontal cortex and right cingulate cortex during memory encoding, but increased activation in the right inferior frontal gyrus (IFG) during recognition memory. While a strong association between hippocampal and parahippocampal activation during memory encoding with subsequent memory performance became evident in healthy controls, this relationship was absent in patients with depression. Taken together, these findings demonstrate that memory related brain regions are affected in their appropriate functioning during memory encoding in depressed patients. Therefore, patients with depression may rely to a greater degree on other brain regions such as the IFG during episodic memory retrieval. Hum Brain Mapp 35:4293–4302, 2014. © 2014 Wiley Periodicals, Inc.
GLUCAN PHOSPHATE TREATMENT ATTENUATES BURN-INDUCED INFLAMMATION AND IMPROVES RESISTANCE TO PSEUDOMONAS AERUGINOSA BURN WOUND INFECTION

These studies evaluated the effects treatment with glucan phosphate, a soluble polysaccharide immunomodulator, on the inflammatory response induced by burn injury and on resistance to Pseudomonas aeruginosa burn wound infection. Mice were exposed to 35% total body surface area burns and were resuscitated with lactated Ringer's (LR) solution alone or LR supplemented with glucan phosphate (40 mg/kg). Glucan phosphate treatment attenuated burn-induced expression of interleukin (IL)-1β, IL-6, and IL-10 mRNAs in spleen, lung, and heart. Plasma concentrations of IL-1β, IL-6, macrophage inflammatory protein (MIP)-2, and IL-10 were also decreased in burned mice treated with glucan phosphate compared with vehicle-treated controls. Early postburn mortality was not significantly different between control (20%) and glucan phosphate-treated (10%) mice, but there was a small improvement in acid-base balance in the glucan phosphate-treated group. Mice received a second injection of glucan phosphate or LR on day 4 postburn and were infected by topical application of P. aeruginosa to the burn wound on day 5. Glucan phosphate treatment significantly improved survival in mice exposed to P. aeruginosa burn wound infection. The improved survival correlated with lower bacterial burden in the burn wound, attenuated production of proinflammatory cytokines, and enhanced production of Th1 cytokines. These studies show that glucan phosphate treatment attenuates burn-induced inflammation and increases resistance to P. aeruginosa burn wound infection in an experimental model of burn injury.
Survivin Expression Quantified by Image Pro-plus Compared With Visual Assessment

Over the past decades, immunohistochemistry has gained significance and already taken a crucial position in diagnosis of diseases and prognosis of patients. However, manual interpretation of immunohistochemistry and reproducibility of the scoring systems can be highly subjective. In the article, the immunohistochemical staining of survivin in 98 rectal cancers was analyzed by using Image Pro-Plus (IPP) [3 parameters: density mean, area sum, and integrated optical density (IOD)] and the results were compared with visual assessment (2 parameters: intensity and percentage). The correlations between the 2 methods were examined, significant correlations were observed between density mean and staining intensity (Spearman correlation coefficient, rs=0.806, P<0.001), IOD and staining intensity (rs=0.914, P<0.001), area sum and staining percentage (rs=0.883, P<0.001), IOD and staining percentage (rs=0.884, P<0.001). There was no significant difference between survivin expression and clinicopathologic variables (P>0.05) by visual assessment. However, by IPP analysis, both the density mean and IOD were higher in better-differentiated cancers than in worse differentiated ones (P=0.02 and 0.03). There was a substantial agreement between the 2 methods. Density mean and IOD of IPP were representative parameters to assess the immunostaining quantification, and increased sensitivity in scoring and provided a more reliable and reproducible analysis of protein expression, especially, more information of the protein expression in relation to clinicopathologic variables can be provided by IPP analysis.
Transplantation of GABAergic Cells Derived from Bioreactor-Expanded Human Neural Precursor Cells Restores Motor and Cognitive Behavioral Deficits in a Rodent Model of Huntington's Disease

Huntington's disease (HD) is a neurodegenerative disorder that is characterized by progressive dementia, choreiform involuntary movements, and emotional deterioration. Neuropathological features include the progressive degeneration of striatal γ-aminobutyric acid (GABA) neurons. New therapeutic approaches, such as the transplantation of human neural precursor cells (hNPCs) to replace damaged or degenerated cells, are currently being investigated. The aim of this study was to investigate the potential for utilizing telencephalic hNPCs expanded in suspension bioreactors for cell restorative therapy in a rodent model of HD. hNPCs were expanded in a hydrodynamically controlled and homogeneous environment under serum-free conditions. In vitro analysis revealed that the bioreactor-expanded telencephalic (BET)-hNPCs could be differentiated into a highly enriched population of GABAergic neurons. Behavioral assessments of unilateral striatal quinolinic acid-lesioned rodents revealed a significant improvement in motor and memory deficits following transplantation with GABAergic cells differentiated from BET-hNPCs. Immunohistochemical analysis revealed that transplanted BET-hNPCs retained a GABAergic neuronal phenotype without aberrant transdifferentiation or tumor formation, indicating that BET-hNPCs are a safe source of cells for transplantation. This preclinical study has important implications as the transplantation of GABAergic cells derived from predifferentiated BET-hNPCs may be a safe and feasible cell replacement strategy to promote behavioral recovery in HD.
The Molecular Genetics of Feline Coronaviruses: Comparative Sequence Analysis of the ORF7a/7b Transcription Unit of Different Biotypes

Abstract Feline coronaviruses (FCoVs) have been subdivided into feline enteric coronaviruses (FECVs) and feline infectious peritonitis viruses (FIPVs) on the basis of pathogenic properties. Serologically, a distinction has been made between type I and II FCoVs, the latter of which more closely resemble canine coronavirus (CCV). To gain more insight into the genetic relationships between different FCoV biotypes, we determined the nucleotide sequences of the ORF7a/7b transcription unit of nine strains. The following observations were made: (i) The sequences are 87-100% identical. In this part of the genome, type I and II FCoVs are more closely related to each other than to CCV. To explain the genetic and antigenic differences between the spike genes of type I and II FCoVs, we postulate that type II FCoVs have arisen by an RNA recombination event between a type I FCoV and CCV. (ii) The avirulent "FECV" strains UCD and 79-1683 are more similar to virulent "FIPV" strains than to each other. Our findings thus support the notion that FECV and FIPV are not different species but merely virulence variants. (iii) In contrast to FECV 79-1683, FECV UCD contains an intact ORF7b, indicating that ORF7b deletions are not a universal distinguishing property of FECVs. (iv) ORF7b deletions readily occur in vitro, correlating with loss of virulence. By reverse transcription polymerase chain reaction analysis, we show that in naturally occurring FCoVs ORF7b is maintained Thus, ORF7b seems to provide a distinct selective advantage during natural infection.
A comparison of two pachymetric systems: slit-scanning and ultrasonic.

PURPOSE This article compares measurements of corneal thickness obtained with the Orbscan Topography System with those obtained with the ultrasonic pachymeter, when used to measure central-comeal thickness in normal subjects. METHODS Slit-scan topography (Orbscan II system, version 3.0, Bausch & Lomb, Rochester, NY) and ultrasonic pachymetry (Ophthasonic A-Scan/ Pachometer III, Accutome, Malvern, PA) were used to measure central-corneal thickness in 92 right corneas of 92 healthy adult subjects. A correlation analysis was used to evaluate the relationship between both instruments. Measurements were also compared by plotting the difference between the methods against the average. The hypothesis of zero bias was examined by a paired t-test. The 95% limits of agreement also were calculated. RESULTS The mean corneal thickness was 559.9 microm +/-3.73 SEM with the Orbscan system and 551.2 microm +/- 4.57 SEM with the ultrasonic pachymeter, values that were significantly different (paired t-test, P = 0.000). The coefficient of determination was 0.860 (y = -65.78 + 1.135 x; P = 0.000). The mean difference between the measurements from both devices was found to be significantly different from zero (mean: 8.74 microm; paired t-test; P = 0.000), with Orbscan being slightly higher than the Ophthasonic A-Scan. CONCLUSIONS The Orbscan system measurements of central corneal thickness were greater than ultrasonic pachymeter measurements, a difference that was statistically significantly.
Inhibitory Effects of Key Compounds Isolated from Corni fructus on BACE1 Activity

Progressive cerebral deposition of Aβ in the brain is a seminal event in the pathogenesis of Alzheimer's disease (AD). Aβ is generated from the amyloid precursor protein (APP) by proteolytic processing of β‐secretase (BACE1) and γ‐secretase. Consequently, BACE1, a key enzyme in the production of Aβ, is a prime target for therapeutic intervention in AD. In the course of screening for natural BACE1 inhibitors from Corni fructus, the ethyl acetate (EtOAc) fraction showed significant inhibitory activity against BACE1. By activity guided purification, three compounds of BACE1 inhibitors p‐coumaric acid, gallic acid and ursolic acid were isolated from Corni fructus EtOAc fraction. All isolated compounds suppressed BACE1 in a dose dependent manner. p‐Coumaric acid, in particular, exhibited significant inhibitory activity against BACE1 with 9.0 × 10‐5 m and a Ki value of 1.9 × 10‐6 m. Also this compound was non‐competitive with a substrate in the Dixon plot, suggesting that it might bind either to the β‐secretase subsite or to another regulatory site. All compounds showed no significant attenuation of TACE (α‐secretase) and other serine proteases such as chymotrypsin and trypsin, demonstrating that they were relatively selective and specific inhibitors of BACE1. These novel findings suggest that Corni fructus contains biologically active components that may be used to attenuate the progression and/or prevention of Alzheimer's disease. Copyright © 2012 John Wiley & Sons, Ltd.
ORIGINAL RESEARCH—COUPLES' SEXUAL DYSFUNCTIONS: Prostate Cancer Patients and Their Partners: Differences in Satisfaction Indices and Psychological Variables

ABSTRACT Introduction Prostate cancer is the most common type of cancer found in American men. Patient adjustment to prostate cancer is not limited to attempts to restore sexual function, a process that can pose significant challenges to couples following most surgical and nonsurgical treatments. Patients often struggle with depression and other relational stressors. Partners also undergo psychosocial, relational, sexual, and quality-of-life changes and their responses to these changes may relate to patient adjustment. Aim To evaluate to what extent partners' psychosocial and relational adjustment relates to prostate cancer patient adjustment. Main Outcome Measures Partner and patient general and sexual depression; patient relationship satisfaction, quality of sexual communication, sexual satisfaction, and life satisfaction. Method A total of 77 patients and 57 partners responded to a mail survey that included demographic information, the Beck Depression Inventory, Life Satisfaction Index, Index of Sexual Satisfaction, Relationship Assessment Scale, Dyadic Sexual Communication Scale, Sexuality Scale, and Client Satisfaction Questionnaire. Results Patients and their partners differed in their sexual self-esteem, sexual depression, sexual preoccupation, and life satisfaction. Both had greater levels of depression, poorer quality of sexual communication, and more sexual dissatisfaction than the general population. Partners' level of general depression and depression concerning their sex lives were significant predictors of patients' relationship satisfaction, perceived quality of communication about the sexual relationship, and sexual satisfaction after controlling for patients' general and sexual depression. Conclusions Partners often serve as primary caregivers, thus partner adjustment can be critical to the health of the patient and to his primary relationship. Results suggest the importance of including partners' adjustment in assessing patient adjustment post-treatment. We suggest that physicians working with these patients partner with mental health professionals who can help couples address the challenges they encounter and extend the continuity of care when the need for medical intervention has passed. Garos S, Kluck A, and Aronoff D. Prostate cancer patients and their partners: Differences in satisfaction indices and psychological variables.
Levels of Antibody to Conserved Parts of Plasmodium falciparum Merozoite Surface Protein 1 in Ghanaian Children Are Not Associated with Protection from Clinical Malaria

ABSTRACT The 19-kDa conserved C-terminal part of the Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is a malaria vaccine candidate antigen, and human antibody responses to PfMSP119 have been associated with protection against clinical malaria. In this longitudinal study carried out in an area of stable but seasonal malaria transmission with an estimated parasite inoculation of about 20 infective bites/year, we monitored 266 3- to 15-year-old Ghanaian children clinically and parasitologically over a period of 18 months. Blood samples were collected at the beginning of the study before the major malaria season in April and after the season in November. Using enzyme-linked immunosorbent assay, we measured antibody responses to recombinant gluthathioneS-transferase–PfMSP119 fusion proteins corresponding to the Wellcome and MAD20 allelic variants in these samples. Prevalence of antibodies recognizing the Wellcome 19 construct containing both epidermal growth factor (EGF)-like motifs in Wellcome type PfMSP119 was about 30%. Prevalence of antibodies to constructs containing only the first EGF domain from either Wellcome or MAD20 type PfMSP119 was about 15%, whereas antibodies recognizing a construct containing only the second EGF domain of MAD20 type PfMSP119 was found in only about 4% of the donors. Neither the prevalence nor the levels of any of the antibody specificities varied significantly with season, age, or sex. Significantly, and in contrast to previous reports from other parts of West Africa, we found no evidence of an association between antibody responses to PfMSP119and clinical protection against malaria.