Miracle-dz/UniFAR-FTUs huggingface dataset:
Reasons for poor accrual in palliative radiation therapy research studies.

BACKGROUND Patients with advanced-stage cancer commonly have multiple symptoms, poor performance status, and limited life expectancies. Despite the need for evidence-based practice and guidelines for palliative radiation therapy (RT), conducting clinical palliative research has proven to be a challenge in the past because of low accrual rates and high patient attrition. We explore the change in accrual rates, reasons for nonparticipation in palliative RT clinical research trials, and factors that contributed to the increase in accrual over a 3-year period. PATIENTS AND METHODS A record was kept for all patients seen at the Rapid Response Radiotherapy Program between 2002 and 2005, including information on patient demographics, disease characteristics, and whether patients were accrued into >/=1 palliative research study at the time of clinic visit. If a patient did not participate in a study, the reason for nonaccrual was recorded. RESULTS Despite previous difficulties, changes to the methods of conducting palliative research and study design have resulted in an increase in patient accrual, from 14% to an average of approximately 60%. The implementation of a full-time clinical research assistant and a simple study design with realistic eligibility criteria contributed to the increase in patient participation. CONCLUSION Difficulties in conducting palliative clinical research trials were improved through changes in study design and research administration. Future clinics should use a dedicated clinical research assistant responsible for patient recruitment and study management. Studies should be designed specifically for the patient population receiving palliative care and should involve clearly defined and realistic eligibility criteria and brief assessments.
Antifungal Susceptibility of 596 Aspergillus fumigatus Strains Isolated from Outdoor Air, Hospital Air, and Clinical Samples: Analysis by Site of Isolation

ABSTRACT We analyzed the activities of six antifungal drugs (amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin, and micafungin) against 596 Aspergillus fumigatus strains isolated from outdoor air, hospital air, and clinical samples. We did not find differences among the susceptibilities by site of isolation.
Chronic nicotine in hearts with healed ventricular myocardial infarction promotes atrial flutter that resembles typical human atrial flutter.

The potential of chronic nicotine exposure for atrial fibrillation (AF) and atrial flutter (AFL) in hearts with and without chronic myocardial infarction (MI) remains poorly explored. MI was created in dogs by permanent occlusion of the left anterior descending coronary artery, and dogs were administered nicotine (5 mg.kg(-1). day(-1) sc) for 1 mo using osmotic minipumps. High-resolution epicardial (1,792 bipolar electrodes) and endocardial Halo catheters were used to map activation during induced atrial rhythms. Nicotine promoted inducible sustained AFL at a mean cycle length of 134 +/- 10 ms in all MI dogs (n = 6) requiring pacing and electrical shocks for termination. No AFL could be induced in MI dogs (n = 6), control (non-MI) dogs (n = 3) not exposed to nicotine, and dogs with no MI and exposed to nicotine (n = 3). Activation maps during AFL showed a single reentrant wavefront in the right atrium that rotated either clockwise (60%) or counterclockwise (40%) around the crista terminalis and through the isthmus. Ablation of the isthmus prevented the induction of AFL. Nicotine caused a significant (P < 0.01) but highly heterogeneous increase in atrial interstitial fibrosis (2- to 10-fold increase in left and right atria, respectively) in the MI group but only a 2-fold increase in the right atrium in the non-MI group. Nicotine also flattened (P < 0.05) the slope of the epicardial monophasic action potential duration (electrical restitution) curve of both atria in the MI but not in non-MI dogs. Two-dimensional simulation in an excitable matrix containing an isthmus and nicotine's restitutional and reduced gap junctional coupling (fibrosis) parameters replicated the experiments. Chronic nicotine in hearts with MI promotes AFL that closely resembles typical human AFL. Increased atrial interstitial fibrosis and flattened electrical restitution are important substrates for the AFL.
CRF22_01A1 is Involved in the Emergence of New HIV-1 Recombinants in Cameroon

Abstract: Cameroon is a West African country where high genetic diversity of HIV-1 has been reported. The predominant CRF02_AG is involved in the emergence of more complex intersubtype recombinants. In this study, we sequenced the full-length genome of a novel unique recombinant form of HIV-1, 02CAMLT04 isolated in blood donors in urban Cameroon. Phylogenetic tree and bootscan analysis showed that 02CAMLT04 was complex and seemed to be a secondary recombinant derived from CRF02_AG and CRF22_01A1. The genomic composition of 02CAMLT04 strain showed that it is composed of 3 segments; 24% of the genome is classified as CRF02_AG, spanning most of the envelope gene. The remaining 76% of the genome is classified as CRF22_01A1. In addition, the sequence analysis of 13 full-length sequences from HIV-1–positive specimens received from Cameroon between 2002 and 2010 indicated that 5 specimens are pure CRF22_01A1 viruses, and 6 others have homology with CRF22_01A1 sequences in either gag, pol, or env region, whereas 6% of strains contain portions of CRF22_01A1. Further study demonstrated that CRF22_01A1 is a primary prevalence strain co-circulating in Cameroon and is involved in complex intersubtype recombination events with subtypes (D or F), subsubtypes (A1 or F2), and CRFs (CRF01_AE or CRF02_AG). Our studies show that novel recombinants between CRF22_01A1 and other clades and recombinant forms may be emerging in Cameroon that could contribute to the future global diversity of HIV-1 in this region and worldwide.
What Do We Learn from Public Good Games About Voluntary Climate Action? Evidence from an Artefactual Field Experiment

Evidence from public good game experiments holds the promise of instructive and cost-effective insights to inform environmental policy-making, for example on climate change mitigation. To fulfill the promise, such evidence needs to demonstrate generalizability to the specific policy context. This paper examines whether and under which conditions such evidence generalizes to voluntary mitigation decisions. We observe each participant in two different decision tasks: a real giving task in which contributions are used to directly reduce CO2 emissions and a public good game. Through two treatment variations, we explore two potential shifters of generalizability in a within-subjects design: the structural resemblance of contribution incentives between the tasks and the role of the subject pool, students and non-students. Our findings suggest that cooperation in public good games is linked to voluntary mitigation behavior, albeit not in a uniform way. For a standard set of parameters, behavior in both tasks is uncorrelated. Greater structural resemblance of the public goods game leads to sizable correlations, especially for student subjects.
The role of solvent pressure in osmotic systems.

and if En = An-a, a > 1/q, the second member of (26) becomes Anj1q-1IP-a* For q > 1 there is in the real domain an intimate connection between degree of convergence in the qth power mean of trigonometric polynomials on the one hand, and integrated Lipschitz conditions on the other, first indicated by Hardy and Littlewood, then developed in detail by Quade, and later by Zygmund. Instead of using integrated Lipschitz conditions, one may use fractional derivatives, introduced into the theory of approximation by trigonometric polynomials by M\Iontel (1918). Interrelations among these properties were developed by Ogieveckil,2 who seems, however, not to have proved the properties expressed in Theorem 9 relating approximation of one and the same function as measured by means of two different orders. Ogieveckil does not treat the cases p < 1 or q < 1.
Levels of expression of complement regulatory proteins CD46, CD55 and CD59 on resting and activated human peripheral blood leucocytes

The cell surface complement regulatory (CReg) proteins CD46, CD55 and CD59 are widely expressed on human lymphoid and non‐lymphoid cells. This study aimed to compare systematically levels of CReg expression by different leucocyte subsets and to determine whether levels were increased following activation in vitro. Levels of each CReg protein were similar on freshly isolated monocytes and all major lymphocyte subsets, except that CD4+ cells expressed significantly less CD46 than CD8+ cells (P < 0·05) while the reverse was observed for CD55 (P < 0·02). CD56+ cells, predominantly natural killer cells, expressed significantly lower levels of CD59 than T cells (P < 0·02). CD45RO+ cells had higher levels of surface CD46 and CD59, but lower levels of CD55, than CD45RO– cells (P < 0·02); CD25+ cells also expressed significantly less CD55 than CD25– cells (P < 0·002). Neutrophils expressed higher levels of CD59, but lower levels of CD55, than monocytes. Following activation with phytohaemagglutinin, CD46 was up‐regulated on all leucocyte subsets with the exception of CD56+ cells. Both CD55 and CD59 were also markedly up‐regulated on monocytes, and CD55 expression was greater on CD8+ than CD4+ cells following activation (P < 0·02). Lipopolysaccharide treatment did not significantly alter B‐cell expression of CReg proteins whereas CD55 and CD59, but not CD46, were significantly up‐regulated on monocytes (P < 0·02). These observations that CReg proteins are up‐regulated on certain activated leucocyte subsets indicate that levels would be increased following immune responses in vivo. This could enhance both protection against local complement activation at inflammatory sites and also the immunoregulatory properties of these leucocytes.
Trabecular Bone Turnover and Bone Marrow Cell Development in Tail‐Suspended Mice

To clarify the relationship between the changes of trabecular bone turnover and bone marrow cell development during mechanical unloading and reloading, we performed experiments with tail‐suspended mice. At 8 weeks of age, 150 male ddY mice were divided into three body weight‐matched groups. Mice of group 1 were euthanized at the start of tail suspension (day 0) as a baseline control. The mice of group 2 were subjected to hindlimb unloading by tail suspension for 14 days and reloading for the subsequent 14 days. The mice of group 3 were normally loaded as age‐matched controls. Mice of groups 2 and 3 were sacrificed at 7, 14, and 28 days after the start of the experiment. In the first experiment (histomorphometric study of tibiae), unloading for 7 and 14 days and reloading for the subsequent 14 days significantly decreased the bone volume compared with that in the age‐matched controls, respectively. Unloading for 7 and 14 days also significantly reduced the bone formation rate (BFR/BS), respectively, but reloading for the subsequent 14 days restored BFR/BS to the control level. While the unloading for 7 and 14 days significantly increased both the osteoclast surface (Oc.S/BS) and the osteoclast number (Oc.N/BS), the reloading for the subsequent 14 days decreased Oc.S/BS and Oc.N/BS, respectively. In the second experiment (bone marrow cell culture study of tibiae), unloading for 7 and 14 days reduced the adherent stromal cell number, without significance. Unloading for 7 days significantly decreased the mineralized nodule formation. Reloading for the subsequent 14 days markedly increased the adherent stromal cell number and the mineralized nodule formation. Unloading for 7 days significantly increased the number of tartrate‐resistant acid phosphatase (TRAP)‐positive multinucleated cells. These data clearly demonstrate that unloading reduces bone formation and increases bone resorption, and subsequent reloading restores reduced bone formation and suppresses increased bone resorption, closely associated with the changes in adherent stromal cell number, mineralized nodule formation, and the number of TRAP‐positive multinucleated cells.
Getting results for hematology patients through access to the electronic health record.

PURPOSE To conduct a needs assessment to identify patient and provider perceptions about providing patients with access to their electronic health record in order to develop an online system that is appropriate for all stakeholders. METHODS Malignant hematology patients were surveyed and health care providers were interviewed to identify issues and validate concerns reported in the literature. Based on the analysed data, a prototype will be designed to examine the feasibility and efficacy of providing patients with access to their electronic health record and tailored information. RESULTS 61% of patients reported using the internet to find health information; 89% were interested in accessing their electronic health record and 79% stated they would benefit from educational material along with the results. Staff members viewed patient online access to the record favourably, but expressed the importance of providing the necessary patient support and education. A Web-based prototype was developed for patients to review their registration data and blood results. CONCLUSIONS Hematology oncology patients are more interested in using the internet to monitor their clinical information than to find health information. Using the constructed prototype, the feasibility of this project is currently being tested.
Concerning ionizing radiation-induced cancer from internally deposited radionuclides

Purpose: A comparative evaluation was conducted of ionizing radiation-induced cancer from internally deposited radionuclides. Materials and methods: Data were evaluated for humans for 226Ra, and for laboratory animal studies for alpha-emitters 228Ra, 226Ra, 224Ra, 238Pu, 239Pu, 228Th, 252Cf, 249Cf, and 241Am, and for beta-emitters 90Sr, 90Y, 91Y, and 144Ce. Intake routes included ingestion, inhalation, and injection. Results: Cancer risk associated with protracted ionizing radiation exposure is a non-linear function of lifetime average dose rate to the affected tissues. The lifetime effects are best described by three-dimensional average-dose-rate/time/response surfaces that compete with other causes of death during an individual's lifetime. At the higher average dose rates the principal deleterious effects are those associated with radiation-induced injury, while at intermediate average dose rates radiation-induced cancer predominates. Conclusions: The cumulative radiation dose is neither an accurate nor an appropriate measure of cancer risk associated with protracted ionizing radiation exposure. At low average dose rates the long latency time required for radiation-induced cancer may exceed the natural lifespan yielding a lifespan virtual threshold for radiation-induced cancer for cumulative doses below about 5–10 Sv for bone, bone marrow and lungs.
Dynamic but not constitutive association of calmodulin with rat TRPV6 channels enables fine tuning of Ca2+‐dependent inactivation

The Ca2+‐selective TRPV6 as well as the L‐type Ca2+ channel are regulated by the Ca2+‐binding protein calmodulin (CaM). Here, we investigated the interaction of CaM with rat (r)TRPV6 in response to alterations of intracellular Ca2+, employing Ca2+‐imaging and patch‐clamp techniques. Additionally, confocal Förster resonance energy transfer (FRET) microscopy on living cells was utilized as a key method to visualize in vivo protein–protein interactions essential for CaM regulation of rTRPV6 activity. The effects of overexpressed CaM or its Ca2+‐insensitive mutant (CaMMUT) was probed on various rTRPV6 mutants and fragments in an attempt to elucidate the molecular mechanism of Ca2+/CaM‐dependent regulation and to pinpoint the physiologically relevant rTRPV6–CaM interaction site. A significant reduction of rTRPV6 activity, as well as an increase in current inactivation, were observed when CaM was overexpressed in addition to endogenous CaM. The Ca2+‐insensitive CaMMUT, however, failed to affect rTRPV6‐derived currents. Accordingly, live cell confocal FRET microscopy revealed a robust interaction for CaM but not CaMMUT with rTRPV6, suggesting a strict Ca2+ dependence for their association. Indeed, interaction of rTRPV6 or its C terminus with CaM increased with rising intracellular Ca2+ levels, as observed by dynamic FRET measurements. An rTRPV6Δ695–727 mutant with the very C‐terminal end deleted, yielded Ca2+ currents with a markedly reduced inactivation in accordance with a lack of CaM interaction as substantiated by FRET microscopy. These results, in contrast with those for CaM‐dependent L‐type Ca2+ channel inactivation, demonstrate a dynamic association of CaM with the very C‐terminal end of rTRPV6 (aa 695–727), and this enables acceleration of the rate of rTRPV6 current inactivation with increasing intracellular CaM concentrations.
Quantitative Trait Loci Mapping

Researchers interested in the physical locations of genes that influence a person’s alcohol-related behaviors can use a method known as quantitative trait loci (QTL) mapping to identify the approximate locations of genes in the genome. QTL mapping can use recombinant inbred mouse strains, which are sets of inbred strains derived from cross-breeding the offspring of two genetically distinct parent strains. The inbred strains exhibit different patterns of the parent strains’ genes. QTL mapping involves comparing alcohol-related behaviors in these strains and identifying patterns of known genetic markers shared by strains with the same behaviors. The markers allow the identification of probable locations of genes that influence alcohol-related behaviors. These locations can then be verified using other tests, and specific genes can be sought there.
End-of-life care for older patients with ovarian cancer is intensive despite high rates of hospice use.

PURPOSE To date, few studies have examined end-of-life care for patients with ovarian cancer. One study documented increased hospice use among older patients with ovarian cancer from 2000 to 2005. We sought to determine whether increased hospice use was associated with less-intensive end-of-life medical care. PATIENTS AND METHODS We identified 6,956 individuals age ≥ 66 years living in SEER areas who were enrolled in fee-for-service Medicare, diagnosed with epithelial ovarian cancer between 1997 and 2007, and died as a result of ovarian cancer by December 2007. We examined changes in medical care during patients' last month of life over time. RESULTS Between 1997 and 2007, hospice use increased significantly, and terminal hospitalizations decreased (both P < .001). However, during this time, we also observed statistically significant increases in intensive care unit admissions, hospitalizations, repeated emergency department visits, and health care transitions (all P ≤ .01). In addition, the proportion of patients referred to hospice from inpatient settings rose over time (P = .001). Inpatients referred to hospice were more likely to enroll in hospice within 3 days of death than outpatients (adjusted odds ratio, 1.36; 95% CI, 1.12 to 1.66). CONCLUSION Older women with ovarian cancer were more likely to receive hospice services near death and less likely to die in a hospital in 2007 compared with earlier years. Despite this, use of hospital-based services increased over time, and patients underwent more transitions among health care settings near death, suggesting that the increasing use of hospice did not offset intensive end-of-life care.
Seeding and transgenic overexpression of alpha‐synuclein triggers dendritic spine pathology in the neocortex

Although misfolded and aggregated α‐synuclein (α‐syn) is recognized in the disease progression of synucleinopathies, its role in the impairment of cortical circuitries and synaptic plasticity remains incompletely understood. We investigated how α‐synuclein accumulation affects synaptic plasticity in the mouse somatosensory cortex using two distinct approaches. Long‐term in vivo imaging of apical dendrites was performed in mice overexpressing wild‐type human α‐synuclein. Additionally, intracranial injection of preformed α‐synuclein fibrils was performed to induce cortical α‐syn pathology. We find that α‐synuclein overexpressing mice show decreased spine density and abnormalities in spine dynamics in an age‐dependent manner. We also provide evidence for the detrimental effects of seeded α‐synuclein aggregates on dendritic architecture. We observed spine loss as well as dystrophic deformation of dendritic shafts in layer V pyramidal neurons. Our results provide a link to the pathophysiology underlying dementia associated with synucleinopathies and may enable the evaluation of potential drug candidates on dendritic spine pathology in vivo.
Staphylococcus aureus ClpC Divergently Regulates Capsule via sae and codY in Strain Newman but Activates Capsule via codY in Strain UAMS-1 and in Strain Newman with Repaired saeS

ABSTRACT ClpC is an ATPase chaperone found in most Gram-positive low-GC bacteria. It has been recently reported that ClpC affected virulence gene expression in Staphylococcus aureus. Here we report that ClpC regulates transcription of the cap operon and accumulation of capsule, a major virulence factor for S. aureus. As virulence genes are regulated by a complex regulatory network in S. aureus, we have used capsule as a model to understand this regulation. By microarray analyses of strain Newman, we found that ClpC strongly activates transcription of the sae operon, whose products are known to negatively regulate capsule synthesis in this strain. Further studies indicated that ClpC repressed capsule production by activating the sae operon in strain Newman. Interestingly, the clpC gene cloned into a multiple-copy plasmid vector exhibited an activation phenotype, suggesting that ClpC overexpression has a net positive effect. In the absence of sae function, by either deletion or correction of a native mutation within saeS, we found that ClpC had a positive effect on capsule production. Indeed, in the UAMS-1 strain, which does not have the saeS mutation, ClpC functioned as an activator of capsule production. Our microarray analyses of strain Newman also revealed that CodY, a repressor of capsule production, was repressed by ClpC. Using genetic approaches, we showed that CodY functioned downstream of ClpC, leading to capsule activation both in Newman and in UAMS-1. Thus, ClpC functions in two opposite pathways in capsule regulation in strain Newman but functions as a positive activator in strain UAMS-1.
The Care of Patients with Dementia: A Modern Jewish Ethical Perspective

Patients with dementia and their families can face many difficult and agonizing ethical dilemmas over the course of the illness. An awareness of the Jewish ethical response to some of these issues can help clinicians in treating patients of the Jewish faith and also serve as an example of how one ethical system addresses these questions. The Jewish response is grounded in a profound respect and value for human life in all its forms and man's responsibility to preserve it, but Judaism rejects unproven therapies and recognizes the limitations of modern medicine. Jewish law also codifies normative obligations that children have toward their elderly parents. With these principles in the forefront, this article analyzes a Jewish ethical response to various problems in the care of the demented patient such as truth telling, transfer to a nursing home, artificial nutrition, and end‐of‐life care, taking into account modern concepts of the doctor‐patient relationship and ancient Jewish tradition.