Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical-dosimetric relationship between lacrimal gland dose and ocular toxicity after intensity-modulated radiotherapy for sinonasal tumours.

OBJECTIVE To characterise the relationship between lacrimal gland dose and ocular toxicity among patients treated by intensity-modulated radiotherapy (IMRT) for sinonasal tumours. METHODS 40 patients with cancers involving the nasal cavity and paranasal sinuses were treated with IMRT to a median dose of 66.0 Gy. Toxicity was scored using the Radiation Therapy Oncology Group morbidity criteria based on conjunctivitis, corneal ulceration and keratitis. The paired lacrimal glands were contoured as organs at risk, and the mean dose, maximum dose, V10, V20 and V30 were determined. Statistical analysis was performed using logistic regression and the Akaike information criterion (AIC). RESULTS The maximum and mean dose to the ipsilateral lacrimal gland were 19.2 Gy (range, 1.4-75.4 Gy) and 14.5 Gy (range, 11.1-67.8 Gy), respectively. The mean V10, V20 and V30 values were 50%, 25% and 17%, respectively. The incidence of acute and late Grade 3+ toxicities was 23% and 19%, respectively. Based on logistic regression and AIC, the maximum dose to the ipsilateral lacrimal gland was identified as a more significant predictor of acute toxicity (AIC, 53.89) and late toxicity (AIC, 32.94) than the mean dose (AIC, 56.13 and 33.83, respectively). The V20 was identified as the most significant predictor of late toxicity (AIC, 26.81). CONCLUSION A dose-response relationship between maximum dose to the lacrimal gland and ocular toxicity was established. Our data suggesting a threshold relationship may be useful in establishing dosimetric guidelines for IMRT planning that may decrease the risk of acute and late lacrimal toxicities in the future. ADVANCES IN KNOWLEDGE A threshold relationship between radiation dose to the lacrimal gland and ocular toxicity was demonstrated, which may aid in treatment planning and reducing the morbidity of radiotherapy for sinonasal tumours.
MEF2 responds to multiple calcium‐regulated signals in the control of skeletal muscle fiber type

Different patterns of motor nerve activity drive distinctive programs of gene transcription in skeletal muscles, thereby establishing a high degree of metabolic and physiological specialization among myofiber subtypes. Recently, we proposed that the influence of motor nerve activity on skeletal muscle fiber type is transduced to the relevant genes by calcineurin, which controls the functional activity of NFAT (nuclear family of activated T cell) proteins. Here we demonstrate that calcineurin‐dependent gene regulation in skeletal myocytes is mediated also by MEF2 transcription factors, and is integrated with additional calcium‐regulated signaling inputs, specifically calmodulin‐dependent protein kinase activity. In skeletal muscles of transgenic mice, both NFAT and MEF2 binding sites are necessary for properly regulated function of a slow fiber‐specific enhancer, and either forced expression of activated calcineurin or motor nerve stimulation up‐regulates a MEF2‐dependent reporter gene. These results provide new insights into the molecular mechanisms by which specialized characteristics of skeletal myofiber subtypes are established and maintained.
Associations between BMI and the FTO Gene Are Age Dependent: Results from the GINI and LISA Birth Cohort Studies up to Age 6 Years

Objective: The association between polymorphisms in intron 1 of the fat mass and obesity associated gene (FTO) and obesity-related traits is one of the most robust associations reported for complex traits and is established both in adults and children. However, little is known about the longitudinal dynamics of these polymorphisms on body mass index (BMI), overweight, and obesity. Methods: This study is based on the 2,732 full-term neonates of the German GINI-plus and LISA-plus birth cohorts, for whom genotyping data on the *Both authors contributed equally to this paper **For list of study group members see acknowledgement section FTO variants rs1558902 (T>A) or rs9935401 (G>A) were available. Children were followed from birth up to age 6 years. Up to 9 anthropometric measurements of BMI were obtained. Fractional-Polynomial-GeneralizedEstimation-Equation modeling was used to assess developmental trends and their potential dependence on genotype status. Results: We observed no evidence for BMI differences between genotypes of both variants for the first 3 years of life. However, from age 3 years onwards, we noted a higher BMI for the homozygous minor alleles carriers in comparison to the other two genotype groups. However, evidence for statistical significance was reached from the age of 4 years onwards. Conclusions: This is one of the first studies investigating in detail the development of BMI depending on FTO genotype between birth and the age of 6 years in a birth cohort not selected for the phenotype studied. We observed that the association between BMI and FTO genotype evolves gradually and becomes descriptively detectable from the age of 3 years onwards.
Assessment and Availability of Trauma Care Services in a District Hospital of South India; A Field Observational Study.

OBJECTIVE To assess the availability of trauma care services in a district referral hospital of Southern India. METHODS This was a cross-sectional study being performed during 2013 in a tertiary healthcare centre in Southern Indian. A detailed assessment of trauma care services was done in a 400 bed speciality hospital which is an apex referral hospital in the public health system using a check list based on WHO guidelines for evaluation of essential trauma care services, along with in-depth interviews of hospital stake holders and key informants. RESULTS The hospital had physical infrastructure in terms of emergency room, inpatient wards, operation theatres, intensive care unit and blood bank facilities. The recently constructed designated building for trauma care services was not operational and existing facilities were used beyond capacity. A designated trauma team was lacking and speciality services for managing polytrauma were deficient and thus, existing personnel were performing multiple tasks. Neurosurgeons and rehabilitative nursing staff were unavailable, and a radiographer was not available on a 24/7 basis. Existing nursing personnel had not received any formal training in trauma care and standard operating protocols were not available for trauma care. Resources for acute resuscitation were partially adequate. The hospital lacked adequate resources to manage head, abdomen, chest and spine injuries, and most of the polytrauma cases were referred to nearby city hospitals. CONCLUSION District hospital, the only referral hospital in public health system for trauma victims of that region, had inadequate resources to manage trauma victims, which was probably responsible for delay in trauma care, improper referrals, high cost of care and poor outcomes.
Tuberculosis exposure of patients and staff in an outpatient hemodialysis unit.

BACKGROUND Patients receiving hemodialysis are generally considered to be at increased risk of developing tuberculosis (TB). We evaluated a 13-station chronic outpatient hemodialysis unit associated with a community hospital in northern California. Within 6 months, there were 2 incident source cases in the unit of active smear positive pulmonary tuberculosis; the first in a health care worker (HCW), diagnosed April 3, 1998, and the second in a patient undergoing dialysis treatment in October 1998. We describe the cases; the evaluation of exposures; and the institution of an intentional prospective TB control plan, designed specifically for the unique hemodialysis setting. METHODS We evaluated 23 HCWs twice and 89 patients undergoing hemodialysis treatment who were exposed to case 1 and 38 patients who were exposed to case 2. All 23 HCWs had documented prior negative Sierbert purified protein derivative of tuberculin (PPD) status and were retested at 12 weeks after exposure. None of the patients had documentation of PPD status. All of the patients were skin-tested initially with use of the 2-step method, and those with positive test results were offered isoniazid (INH). RESULTS One of the 23 HCWs' negative baseline PPD skin test status converted after exposure to case 1, and none of the remaining 22 converted after exposure to case 2. Twelve of 89 exposed patients with no prior skin test record had positive results for PPD after initial testing with the 2-step method. Three of the 12 (25%) patients were treated with INH at the discretion of their attending nephrologist. The 77 patients with negative results for PPD still had negative test results when retested at 3 months. None of 38 patients who underwent dialysis on the same schedule as source case 2 had a converted PPD test. Restriction fragment length polymorphism on TB isolates from both source cases ultimately showed them to be unrelated strains. CONCLUSION Our experience with these exposures suggests that TB screening of patient populations undergoing renal dialysis-though they have intrinsic high anergy rates-is advisable with a designed prospective plan before any inadvertent and/or repetitive exposure of that population to active TB. A planned intentional TB control program increases HCW awareness of TB, establishes baselines for evaluation, decreases "panic" in the event of subsequent exposures, and emphasizes the rationale for preventive therapy.
Behavioural profiling of a murine Charcot–Marie–Tooth disease type 1A model

Different features of motor behaviour were studied on a transgenic mouse model of Charcot–Marie–Tooth's disease (CMT). Mutants with 4 or 7 copies of the human PMP22 gene leading to a phenotype significantly close to CMT's disease type 1A were compared with control animals. The aim of the study was to validate this transgenic model and to characterise the impairments occurring in the various lines. Three main types of analysis were performed in 2‐month‐old mice without any peculiar visible deficit: (i) a study of standardised clinical tests (SHIRPA protocol) demonstrated that only a few motor deficits were expressed; (ii) a measurement of general spontaneous activity by means of a commercial video‐tracking system was performed and revealed that the main spontaneous activities were identical in the three lines with, however, some slight localised modifications; and, (iii) by contrast, the three lines respond very differently to the footprints, grip strength, splay test and rotarod test. Even in lines with a significantly limited copy number of the transgene, we observed and quantified impairments. In conclusion, mutants of CMT1A seem to be a very pertinent model of this human pathology and will certainly be useful for therapeutic procedures and for theoretical studies on this disease.
The Relationship between Age and Depressive Symptoms

Objective: The objective is to examine competing explanatory and suppression influences on a negative, linear association between age and depressive symptoms. Methods:Two samples were used: a community sample of physically disabled individuals and a comparison sample matched on age, sex, and area of residence. Results:Fewer economic hardships and fewer experiences of negative interpersonal exchanges among older disabled and nondisabled respondents account for the negative relationship between age and depressive symptoms. Higher scores on a composite measure of religiosity among older disabled adults also account for part of the negative age effect. Conversely, a lower sense of mastery among older respondents in both samples suppresses the size of the negative age slope. Discussion:Findings are discussed in terms of stress process and socioemotional selectivity theories, which predict that personal and social arrangements influence the experience of emotions differentially across the life course.
Profile of Animal Bite Cases in Nanded District of Maharashtra State , India

Rabies is a 100% fatal disease and it can be prevented by post exposure prophylaxis. India contributes the major share of animal bites as well as global deaths due to rabies. To study the profile and extent of use of traditional herbal treatment for animal bite cases the present cross sectional study was carried out. The study consists of 293 animal bite cases attending anti-rabies clinic of Dr. S. C. Govt. Medical College, Nanded in Maharashtra State enrolled by systemic random sampling method. Majority of the study subjects were males from rural area and belonging to socioeconomic class IV and V. Incidence of animal bite was found to be decreased as age advances. A quarter of bites were occurred in children upto 10 years of age and statistically significant provoked bites occurred in children as compared to adolescents and adults. In 92.8% cases bitting animal was dog and most of them were ownerless. 60.7% subjects reported to the health institutes within 24-48 hours after bite. Majority of the bites were of category III and on lower limbs. First aid treatment was received in 47.1% cases and lime application on wound was practiced by 63% subjects. 89.4% subjects were heard about the Kundalwadi’s traditional herbal medicine for treatment of dog bite cases and 24.2% had taken that medicine prior to attend anti-rabies clinic. The sources of information for herbal medicine were neighbours in 39.7% cases and family member in 32.8 % cases.
Multi-Armed Bandits with Non-Stationary Rewards

The multi-armed bandit problem where the rewards are realizations of general non-stationary stochastic processes is a challenging setting which has not been previously tackled in the bandit literature in its full generality. We present the first theoretical analysis of this problem by deriving guarantees for both the path-dependent dynamic pseudo-regret and the standard pseudo-regret that, remarkably, are both logarithmic in the number of rounds under certain natural conditions. We describe several UCB-type algorithms based on the notion of weighted discrepancy, a key measure of non-stationarity for stochastic processes. We show that discrepancy provides a unified framework for the analysis of non-stationary rewards. Our experiments demonstrate a significant improvement in practice compared to standard benchmarks.
Folding behavior of chaperonin‐mediated substrate protein

Chaperonin‐mediated protein folding is complex. There have been diverse results on folding behavior, and the chaperonin molecules have been investigated as enhancing or retarding the folding rate. To understand the diversity of chaperonin‐mediated protein folding, we report a study based on simulations using a simplified Gō‐type model. By considering effects of affinity between the substrate protein and the chaperonin wall and spatial confinement of the chaperonin cavity, we study the thermodynamics and kinetics of folding of an unfrustrated substrate protein encapsulated in a chaperonin cavity. The affinity makes the hydrophobic residues of the protein bind to the chaperonin wall, and a strong (or weak) affinity results in a large (or small) effect of binding. Compared with the folding in bulk, the folding in chaperonin cavity with different strengths of affinity shows two kinds of behaviors: one with less dependence on the affinity but more reliance on the spatial confinement effect and the other relying strongly on the affinity. It is found that the enhancement or retardation of the folding rate depends on the competition between the spatial confinement and the affinity due to the chaperonin cavity, and a strong affinity produces a slow folding while a weak affinity induces a fast folding. The crossover between two kinds of folding behaviors happens in the case that the favorable effect of confinement is balanced by the unfavorable effect of the affinity, and a critical affinity strength is roughly defined. By analyzing the contacts formed between the residues of the protein and the chaperonin wall and between the residues of the protein themselves, the role of the affinity in the folding processes is studied. The binding of the residues with the chaperonin wall reduces the formation of both native contacts and nonnative contact or mis‐contacts, providing a loose structure for further folding after allosteric change of the chaperonin cavity. In addition, 15 single‐site‐mutated mutants are simulated in order to test the validity of our model and to investigate the importance of affinity. Inspiringly, our results of the folding rates have a good correlation with those obtained from experiments. The folding rates are inversely correlated with the strength of the binding interactions, i.e., the weaker the binding, the faster the folding. We also find that the inner hydrophobic residues have larger effects on the folding kinetics than those of the exterior hydrophobic residues. We suggest that, besides the confinement effect, the affinity acts as another important factor to affect the folding of the substrate proteins in chaperonin systems, providing an understanding of the folding mechanism of the molecular chaperonin systems. Proteins 2005. © 2005 Wiley‐Liss, Inc.
[The surgical management of sacral tumors].

OBJECTIVE To investigate the way of sacral tumors surgical treatment. METHODS This retrospective study included 119 cases of sacral tumors surgically treated from July, 1996 to December, 2001. The age of patients ranged from 18 to 80 years (mean 57 years), including of 72 male and 47 female. Out of the patients, there were 52 chordomas, 16 giant cell tumor, 5 neurofibroma, 23 metastases tumors, 9 myeloma, 2 osteoblastomas, 5 aneurysmal bone cysts, 3 osteosarcomas, 4 chondrosarcomas. Posterior approach and combined anterior-posterior approach were used in 83 and 36 cases respectively. Twenty-nine patients had received surgical management at least once and 16 of them had received radiation therapy before came to our department. RESULTS Three patients died on the complication around the surgery. Most of the patients with metastases tumor or multiple myeloma died 1 to 3 years after the surgery. Out of three osteosarcoma patients, 2 died and one alive with tumor. Three chondrosarcoma patients died, and one alive with tumor. Out of 52 chordoma patients, 3 patients had died of metastatic chordoma, 3 patients died of many times recurrence. Among the other 46 patients who were stay alive, 31 were free from disease with average follow-up time of 42 months. In the patients whose sacral nerve roots had been reserved bilaterally at and above S(3) level, the sphincter muscle function of bladder and bowl was good. While the function of sphincter muscle impaired in 2 patients with nerve roots reserved only at and above S(1) level. To manage these 2 patients, indwelling bladder catheters were used, but colostomy had not been performed. CONCLUSIONS Complete resection of tumor (radical surgery when possible) is the most effective way to manage sacral tumors. Postoperative adjuvant radiation therapy can reduce the tumor recurrence rate, but it also can cause troubles that would hinder further surgical managements. Even if the tumor is relatively huge and the upper resection margin is as high as at S(1) or S(2) level, the tumor can be removed successfully by posterior approach and the postoperative complications could be accepted. To the patients with aneurysmal cyst or giant cell tumor on sacrum, for control bleeding purpose, anterior approach should be performed to ligate the bilateral internal iliac artery.
Outage Analysis of Multi-Antenna Cognitive Hybrid Satellite-Terrestrial Relay Networks With Beamforming

This letter investigates the outage performance of a multi-antenna cognitive decode-and-forward (DF) hybrid satellite-terrestrial relay network (HSTRN) with beamforming (BF), where the secondary source and relay can coexist with the primary user (PU) as long as their interference imposed to PU is below a predefined threshold. Specifically, the novel closed-form expression for the outage probability (OP) of the cognitive network are derived. Furthermore, the asymptotic OP expression at high SNR is developed to reveal the diversity order and code gain of the considered network. Finally, simulation results are provided to demonstrate the validity of the theoretical results, and show the effect of antenna number and interfering satellite link on the performance of the cognitive network.
HGF/MET signalling protects Plasmodium‐infected host cells from apoptosis

Plasmodium, the causative agent of malaria, migrates through several hepatocytes before initiating a malaria infection. We have previously shown that this process induces the secretion of hepatocyte growth factor (HGF) by traversed cells, which renders neighbour hepatocytes susceptible to infection. The signalling initiated by HGF through its receptor MET has multifunctional effects on various cell types. Our results reveal a major role for apoptosis protection of host cells by HGF/MET signalling on the host susceptibility to infection. Inhibition of HGF/MET signalling induces a specific increase in apoptosis of infected cells leading to a great reduction on infection. Since HGF/MET signalling is capable of protecting cells from apoptosis by using both PI3‐kinase/Akt and, to a lesser extent, MAPK pathways, we determined the impact of these pathways on Plasmodium sporozoite infection. Although inhibition of either of these pathways leads to a reduction in infection, inhibition of PI3‐kinase/Akt pathway caused a stronger effect, which correlated with a higher level of apoptosis in infected host cells. Altogether, the results show that the HGF/MET signalling requirement for infection is mediated by its anti‐apoptotic signal effects. These results demonstrate for the first time that active inhibition of apoptosis in host cell during infection by Plasmodium is required for a successful infection.
Consortium of the 'bichlorophyllous' cyanobacterium Prochlorothrix hollandica and chemoheterotrophic partner bacteria: culture and metagenome-based description.

'Bacterial consortium' sensu lato applies to mutualism or syntrophy-based systems consisting of unrelated bacteria. Consortia of cyanobacteria have been preferentially studied on Anabaena epibioses; non-photosynthetic satellites of other filamentous or unicellular cyanobacteria were also considered although structure-functional data are few. At the same time, information about consortia of cyanobacteria which have light-harvesting antennae distinct from standard phycobilisome was missing. In this study, we characterized first, via a polyphasic approach, the cultivable consortium of Prochlorothrix hollandica CCAP 1490/1 (filamentous cyanobacterium which contains chlorophylls a, b/carotenoid/protein complex in the absence of phycobilisome) and non-photosynthetic heterotrophic bacteria. The strains of most abundant satellites were isolated and identified. Consortium metagenome reconstructed via 454-pyro and Illumina sequencing was shown to include, except for P. hollandica, several phylotypes of Proteobacteria and Bacteroidetes. The ratio of consortium members was essentially stable irrespective of culture age, and restored after artificially imposed imbalance. The consortium had a complex spatial arrangement as demonstrated by FISH and SEM images of the association, epibiosis, and biofilm type. Preliminary data of metagenome annotation agreed with the hypothesis that satellite bacteria contribute to P. hollandica protection from reactive oxygen species (ROS).