Miracle-dz/UniFAR-FTUs huggingface dataset:
Elderly patients with multiple myeloma: towards a frailty approach?

Purpose of review To describe how to better identify frail multiple myeloma patients and to treat them appropriately. Recent findings Proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, and immunomodulatory agents (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, have significantly improved the outcome of multiple myeloma patients in the last decade. However, both in clinical trials and in daily clinical practice, elderly multiple myeloma patients have shown lesser benefit. This is mainly due to less stringent use of proteasome inhibitors and IMiDs, increased toxicity, and subsequent early discontinuation of therapy in elderly. Summary Multiple myeloma typically affects elderly patients. Approximately one-third of patients are older than 75 years at diagnosis. Moreover, at least 30% are frail, both due to disease-related symptoms and (age-related) decline in physical capacity, presence of comorbidities, frailty, polypharmacy, nutritional status, and cognitive impairment. Treatment regimens that are investigated in clinical trials for transplant-ineligible patients have largely been investigated in fit, rather than frail patients, the latter being typically excluded or highly underrepresented therein. Data on the feasibility and efficacy of current standards of care are therefore lacking in frail patients. Preliminary data suggest a higher toxicity and discontinuation rate, loss of efficacy, and impaired quality of life in frail patients. Geriatric assessment helps to identify frail patients according to their functional and cognitive status. Both the International Myeloma Working Group (IMWG)-frailty index and Revised Myeloma Comorbidity Index constitute recently proposed algorithms that easily identify intermediate-fit and frail patients. Ongoing and future clinical trials, specifically designed for frail patients, will hopefully define frailty-directed treatment selection.
Effect of Exercise Training and Food Restriction on Endothelium-Dependent Relaxation in the Otsuka Long-Evans Tokushima Fatty Rat, a Model of Spontaneous NIDDM

We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic- euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise- trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.
Assessing the Use of FDG-PET in the Detection of Regional and Metastatic Nodes in Alveolar Rhabdomyosarcoma of Extremities

Alveolar rhabdomyosarcoma (ARS) accounts for 20% to 30% of childhood rhabdomyosarcoma and is known to have a worse prognosis than embryonal rhabdomyosarcoma. Metastatic disease is more frequent in patients with alveolar tumors and these children with metastatic disease fare poorly, with a 5-year survival between 20% and 30%. Therefore, ARS represents a significant diagnostic and therapeutic challenge that requires techniques to provide better assessment of the disease than provided by traditional means. F18 fluorodeoxyglucose-positron emission tomography (FDG-PET) depicts the increased metabolism in abnormal tissues, enabling accurate evaluation of suspicious regional and metastatic disease. The new combined PET/CT systems can further improve PET interpretation and affect patient management. The value of FDG in patients with soft tissue sarcomas has been demonstrated in several series, but none specifically in ARS. This report assesses the use of FDG-PET/CT in the detection of regional and metastatic nodes in 3 children diagnosed with ARS of the extremities. All the 3 patients we present had focally increased tracer uptake in nodal stations on a pretherapy PET performed at diagnosis. Tissue confirmation available in 2 patients was negative in 1 patient and positive for metastatic nodal spread in the other. Metastatic axillary disease was possibly also present in the third patient according to his later course of disease.
Basic fibroblast growth factor inhibits ventricular remodeling in Dahl salt-sensitive hypertensive rats

Objective Basic fibroblast growth factor (bFGF) inhibits the progression of ventricular remodeling in ischemic and hypertensive heart diseases (HHDs). Recent studies have revealed that bFGF induces the transition from myofibroblasts to fibroblasts with decreased expression of α-smooth muscle actin (α-SMA). To clarify the mechanisms underlying the reduced ventricular remodeling in hypertensive heart diseases caused by bFGF, we examined the degree of interstitial fibrosis associated with α-smooth muscle actin expression and matrix metalloproteinase activity in hypertensive heart diseases. Methods Dahl salt-sensitive rats were fed with a high-salt diet from 6 to 18 weeks of age and injected with a single dose of bFGF (100 μg) into the left myocardium at 15 weeks. Others were administered PBS without bFGF. Control age-matched Dahl salt-sensitive rats were fed with a low-salt diet. Results Cardiac systolic function was well preserved and decompensation of heart failure was prevented at 18 weeks in the rats treated with bFGF at 15 weeks. The bFGF-treated rats had significantly fewer interstitial α-SMA-positive myofibroblasts and significantly decreased prolyl 4-hydroxylase expression. Increased matrix metalloproteinase-9 gelatinase activity correlated with the downregulation of transforming growth factor-β1 by bFGF, suggesting that inhibited extracellular matrix deposition is associated with a decreased number of myofibroblasts induced by bFGF. Conclusion bFGF can inhibit the progression of ventricular remodeling by inhibiting interstitial fibrosis and promoting angiogenesis without decreasing blood pressure in hypertensive heart disease.
Double‐Blind, Randomized, Placebo‐Controlled, Dose‐Response Study of the Safety and Efficacy of Botulinum Toxin Type A in Subjects with Crow's Feet

Background Published evidence suggests that botulinum toxin type A (BTX-A) is an effective treatment for crow's feet. However, few dose-ranging studies have been performed. Objectives To assess the safety and efficacy of a single treatment with one of four doses of BTX-A (Botox/Vistabel, Allergan Inc) compared with placebo for the improvement of crow's feet. Methods Subjects received a single bilateral treatment of 18, 12, 6, or 3 U of BTX-A or placebo injected into the lateral aspect of the orbicularis oculi muscle (parallel-group, double–blind design). Investigators and subjects rated crow's feet severity at maximum smile on day 7 and at 30-day intervals from days 30 to 180. Results As observed by both investigators and subjects, all doses of BTX-A resulted in improvements in crow's feet severity when compared with placebo. A dose-dependent treatment effect for efficacy was observed, with higher doses having an increased magnitude and duration of effect. However, a clear differentiation between the 18 U and 12 U doses was not apparent. Few adverse events were reported, with no statistically significant differences between BTX-A and placebo in the incidence of subjects experiencing adverse events. Conclusion BTX-A is safe and effective in decreasing the severity of crow's feet, with 12 U per side suggested as the most appropriate dose.
Small artery remodeling is the most prevalent (earliest?) form of target organ damage in mild essential hypertension

Background The heart and blood vessels are exposed to elevated blood pressure (BP) in hypertensive patients, but their changes in response to BP or non-hemodynamic stimuli may be different, and occur with different time-courses. To evaluate this, we studied the prevalence of structural and functional alterations of resistance arteries and cardiac hypertrophy in patients with mild essential hypertension. Methods Resistance arteries were dissected from gluteal subcutaneous tissue from 38 hypertensive patients (47 ± 1 years; 71% male; BP 148 ± 2/99 ± mmHg), studied on a pressurized myograph, and compared to those from 10 normotensives (44 ± 3 years; 40% male; BP 113 ± 4/76 ± 2 mmHg). Results The prevalence of abnormal structure (media-to-lumen ratio, M/L) and impaired endothelial function (maximal acetylcholine response) was 97 and 58% (abnormal was defined as greater than mean + 1SD of normotensives), or 63 and 34% (abnormal defined as greater than mean + 2SD). Thirty four percent of hypertensive patients exhibited left ventricular hypertrophy by echocardiography. When grouped into tertiles according to increasing ambulatory systolic BP (SBP), the highest BP tertile showed increased M/L (P < 0.01) and left ventricular mass index (LVMI, P < 0.05) and marginally decreased endothelial function (P = 0.07). LVMI was greatest in the tertile of patients with highest M/L (P < 0.05). Endothelial function was decreased in the tertile with greatest vascular stiffness (P < 0.01). By multivariate analysis, M/L correlated with ambulatory SBP (β = 0.40, P = 0.02), and LVMI correlated with ambulatory SBP (β = 0.41, P = 0.001) and body mass index (β = 0.30, P < 0.05). Female sex influenced endothelial function negatively (β =− 0.63, P < 0.01). Conclusion Structural alterations of resistance arteries were demonstrated in most hypertensive patients, followed by endothelial dysfunction and cardiac hypertrophy in a smaller number of hypertensives. Small artery structural remodeling may precede most clinically relevant manifestations of target organ damage in mild essential hypertension.
Not to wake a sleeping giant: new insights into host-pathogen interactions identify new targets for vaccination against latent Mycobacterium tuberculosis infection

Abstract Mycobacterium tuberculosis is one of the worlds' most successful and sophisticated pathogens. It is estimated that over 2 billion people today harbour latent M. tuberculosis infection without any clinical symptoms. As most new cases of active tuberculosis (TB) arise from this (growing) number of latently infected individuals, urgent measures to control TB reactivation are required, including post-exposure/therapeutic vaccines. The current bacille Calmette-Guérin (BCG) vaccine and all new generation TB vaccines being developed and tested are essentially designed as prophylactic vaccines. Unfortunately, these vaccines are unlikely to be effective in individuals already latently infected with M. tuberculosis. Here, we argue that detailed analysis of M. tuberculosis genes that are switched on predominantly during latent stage infection may lead to the identification of new antigenic targets for anti-TB strategies. We will describe essential host-pathogen interactions in TB with particular emphasis on TB latency and persistent infection. Subsequently, we will focus on novel groups of late-stage specific genes, encoded amongst others by the M. tuberculosis dormancy (dosR) regulon, and summarise recent studies describing human T-cell recognition of these dormancy antigens in relation to (latent) M. tuberculosis infection. We will discuss the possible relevance of these new classes of antigens for vaccine development against TB.
A new computerised cognitive test for the detection of information processing speed impairment in multiple sclerosis

Background: Cognitive impairment in multiple sclerosis (MS) primarily applies to information processing speed (IPS). Objective: To evaluate psychometric properties of a new digit/symbol substitution test in healthy subjects and patients with MS, and assess its ability to detect IPS impairment in patients with MS. Methods: A sample of MS patients, 60 relapsing–remitting (RRMS) and 41 primary progressive MS (PPMS), and 415 healthy controls (HCs) underwent an IPS battery, including assessment of reaction times of subtests of the Test of Attentional Performance battery and a newly developed in-house digit/symbol substitution task, the Computerised Speed Cognitive Test (CSCT). The CSCT was additionally evaluated in a second cohort of 31 RRMS and 12 progressive MS patients, for comparison with the Symbol Digit Modalities Test (SDMT). Results: The CSCT had good reliability in both HCs and patients with MS. It showed a weak practice effect at the 6-month time point. This test had good ecological validity in MS patients. There was a strong correlation between the CSCT with the SDMT and with other IPS tests in patients with MS. The CSCT had the best sensitivity for predicting IPS impairment and was one of the most accurate tests among the IPS battery. Conclusion: The CSCT appeared as a good candidate for detecting IPS impairment in MS patients.
Capecitabine: effective oral fluoropyrimidine chemotherapy

Fluoropyrimidine chemotherapy, principally with 5-fluorouracil (5-FU), has been a standard of care for a range of solid tumours for many years. Capecitabine, a precursor of 5-FU, is an oral fluoropyrimidine cytotoxic agent developed with the aim of providing a more effective, less toxic alternative to 5-FU, with the added advantage of oral administration. In clinical trials, capecitabine has proven to be an effective substitute for 5-FU in colorectal and breast cancer, and has become an accepted standard treatment in these tumours, both as a single agent and as a component of combination chemotherapy. It is also effective in a number of other solid tumours and as a radiosensitising agent. Capecitabine has significantly less serious toxicity than 5-FU when used alone or in combination with other cytotoxic agents. It has been shown to be resource saving in comparison with accepted standard comparator regimens in breast and colorectal cancer. Ongoing and future clinical trials will continue to examine, and are likely to expand, the role of capecitabine in the treatment of breast and colorectal cancer, as well as a number of other malignancies, both in the advanced palliative and adjuvant curative settings. This will involve the use of capecitabine as a single agent and increasingly in combination with other new anticancer agents.
Advances in how clinical nurses can evaluate and improve quality of life for individuals with cancer.

PURPOSE/OBJECTIVES To describe advances in the ways that clinical nurses understand, assess, and work to improve quality of life (QOL) for individuals with cancer since the 1995 Oncology Nursing Society's State-of-the-Knowledge Conference on QOL. DATA SOURCES Published research and clinical articles. DATA SYNTHESIS The number of QOL assessment tools and methods for understanding QOL results has increased. However, scant literature has focused on how clinical oncology nurses evaluate QOL and the methods they use to affect QOL for individuals with cancer. CONCLUSIONS Based on the nurse-patient relationship, clinical nurses are able to assess QOL in individuals with cancer and intervene appropriately to improve QOL. IMPLICATIONS FOR NURSING Clinical nurses can involve individuals with cancer in rating their QOL to assist in providing high-quality care that is directed at positively affecting QOL.
Treatment of Refractory BK Virus‐Associated Nephropathy With Cidofovir

BK virus‐associated nephropathy (BKVN) has become recognized as an important cause of allograft dysfunction in renal transplant recipients and despite reduction in immunosuppression, 30–40% of recipients ultimately progress to allograft loss. Cidofovir is an antiviral agent that demonstrates in vitro activity against murine polyomavirus and has been proposed for treatment of BKVN in renal allograft recipients. We describe the clinical course, renal function, serial renal histology and urine and blood viral load measurements in two consecutive patients with refractory BKVN who were treated with low‐dose cidofovir (0.25 mg/kg IV). In each case, renal dysfunction and BK viral load progressed despite reduced immunosuppression, and persistent BK virus infection was documented in serial renal allograft biopsy specimens. Administration of low‐dose cidofovir was associated with clearance of BK virus DNA from blood and allograft, and stabilization of renal function in both patients, without significant toxicity. These preliminary data suggest that low‐dose cidofovir may be tolerated, even among renal transplant recipients with significant renal dysfunction due to BKVN. Prospective, controlled trials are warranted to further define the optimal dose, toxicity and potential role of cidofovir in renal transplant recipients with BK virus nephropathy.
Indoor floor-level detection by collectively decomposing factors of atmospheric pressure

This paper presents a novel method for detecting the floor level of a smartphone user in an indoor environment based on the atmospheric pressure measured with sensors in the user's smartphone. Atmospheric pressure is one of the most informative factors when estimating altitude, because its relative variation has a strong correlation with changes in altitude. However, it is difficult to directly estimate the altitude based on an observation of the absolute pressure via smartphones, owing to individual differences in the sensors and changes in climate. In this paper, we propose a robust method for estimating the floor level by decomposing the observed pressure into three components. The first component is the change in altitude, and this component is the primary measure. The second is the global variation, such as changes in climate. The third concerns device-dependent variation. We utilize localization infrastructure, such as beacons or Wi-Fi access points, sparsely located in the environment, because such localization mechanisms can provide floor-level information. Exploiting this mechanism, time-series references to the pressure on each floor level can be generated collectively by aggregating readings from the pressure sensors of multiple users. Using these as a reference, each output of the pressure can be decomposed into device-specific offsets, environmental trends, and the altitude-dependent component. By extracting the altitude-dependent component, the floor level of the user can be estimated robustly without relying on fixed observations of atmospheric pressure.
Neuron‐specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD‐knockout mice

Deletion of copper‐zinc superoxide dismutase (CuZnSOD) in Sod1–/– mice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle‐specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sod1–/– mice in which CuZnSOD was expressed under control of the synapsin 1 promoter (SynTgSod1–/– mice). SynTgSod1–/– mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSod1–/– mice was ~20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTg‐Sod1–/– mice compared with control animals, whereas muscles of age‐matched Sod1–/– mice displayed 30–40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sod1–/– mice were absent in SynTgSod1–/– mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1–/– mice but not in SynTgSod1–/– mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1–/– mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging. —Sakellariou, G. K. , Davis, C. S. , Shi, Y. , Ivannikov, M. V. , Zhang, Y. , Vasilaki, A. , Macleod, G. T. , Richardson, A. , Van Remmen, H. , Jackson, M. J., McArdle, A. , Brooks, S. V. Neuron‐specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD‐knockout mice. FASEB J. 28, 1666‐1681 (2014). www.fasebj. org
A Randomized Controlled Trial of Mindfulness-Based Stress Reduction for Women With Early-Stage Breast Cancer Receiving Radiotherapy

Purpose. To testthe relative effectiveness of a mindfulness-based stress reduction program (MBSR) compared with a nutrition education intervention (NEP) and usual care (UC) in women with newly diagnosed early-stage breast cancer (BrCA)undergoing radiotherapy. Methods. Datawere available from a randomized controlled trialof 172 women, 20 to 65 years old, with stage I or II BrCA. Data from women completing the 8-week MBSR program plus 3 additional sessions focuses on special needs associated with BrCA were compared to women receiving attention control NEP and UC. Follow-up was performed at 3 post-intervention points: 4 months, and 1 and 2 years. Standardized, validated self-administered questionnaires were used to assess psychosocial variables. Descriptive analyses compared women by randomization assignment. Regression analyses, incorporating both intention-to-treat and post hoc multivariable approaches, were used to control for potential confounding variables. Results. A subset of 120 women underwent radiotherapy; 77 completed treatment prior to the study, and 40 had radiotherapy during the MBSR intervention. Women who actively received radiotherapy (art) while participating in the MBSR intervention (MBSR-art) experienced a significant (P < .05) improvement in 16 psychosocial variables compared with the NEP-art, UC-art, or both at 4 months. These included health-related, BrCA-specific quality of life and psychosocial coping, which were the primary outcomes, and secondary measures, including meaningfulness, helplessness, cognitive avoidance, depression, paranoid ideation, hostility, anxiety, global severity, anxious preoccupation, and emotional control. Conclusions. MBSR appears to facilitate psychosocial adjustment in BrCA patients receiving radiotherapy, suggesting applicability for MBSR as adjunctive therapy in oncological practice.
Effects of Industrial Detergents on the Barrier Function of Human Skin

Abstract Detergents are involved in the causation of contact dermatitis and in promoting percutaneous absorption of toxic chemicals, but limited information is available to allow an assessment of their relative effects on the skin barrier function. The effect of detergents on skin permeability to water and nickel was examined in an in-vitro model using human skin. Twenty four of the most widely used detergents were studied. After a two-hour exposure to an aqueous detergent solution, penetration of labeled model compounds was followed for 66 hours. Interindividual variation was substantial, but 12 of the detergents caused statistically significant increases in the penetration of water, nickel, or both. Nonionic detergents were as likely as anionic detergents to have this effect. This study demonstrates that useful information may be obtained by a simple in-vitro method, and that such data may provide a basis for substitution efforts.