Miracle-dz/UniFAR-FTUs huggingface dataset:
Moving beyond Karnofsky and ECOG Performance Status Assessments with New Technologies

Progress in cancer research is coupled with increased treatment complexity reliant upon accurate patient selection. Oncologists rely upon measurement instruments of functional performance such as the Karnofsky or Eastern Cooperative Oncology Group Performance Status scales that were developed over fifty years ago to determine a patient's suitability for systemic treatment. These standard assessment tools have been shown to correlate with response to chemotherapy, chemotherapy tolerability, survival, and quality of life of cancer patients. However, these scales are subjective, subject to bias and high interobserver variability. Despite these limitations important clinical decisions are based on PS including eligibility for clinical trials, the “optimal” therapeutic approach in routine practice, and the allocation of healthcare resources. This paper reviews the past, present, and potential future of functional performance status assessment in an oncology setting. The potential ability of electronic activity monitoring systems to provide an objective, accurate measurement of patient functional performance is explored. Electronic activity monitoring devices have the potential to offer positive health-related opportunities to patients; however their introduction to the healthcare setting is not without difficulty. The potential role of this technology in healthcare and the challenges that these new innovations pose to the healthcare industry are also examined.
Rural and remote care

The challenges of providing quality respiratory care to persons living in rural or remote communities can be daunting. These populations are often vulnerable in terms of both health status and access to care, highlighting the need for innovation in service delivery. The rapidly expanding options available using telehealthcare technologies have the capacity to allow patients in rural and remote communities to connect with providers at distant sites and to facilitate the provision of diagnostic, monitoring, and therapeutic services. Successful implementation of telehealthcare programs in rural and remote settings is, however, contingent upon accounting for key technical, organizational, social, and legal considerations at the individual, community, and system levels. This review article discusses five types of telehealthcare delivery that can facilitate respiratory care for residents of rural or remote communities: remote monitoring (including wearable and ambient systems; remote consultations (between providers and between patients and providers), remote pulmonary rehabilitation, telepharmacy, and remote sleep monitoring. Current and future challenges related to telehealthcare are discussed.
Expression of the pyr Operon of Lactobacillus plantarum Is Regulated by Inorganic Carbon Availability through a Second Regulator, PyrR2, Homologous to the Pyrimidine-Dependent Regulator PyrR1

ABSTRACT Inorganic carbon (IC), such as bicarbonate or carbon dioxide, stimulates the growth of Lactobacillus plantarum. At low IC levels, one-third of natural isolated L. plantarum strains are nutritionally dependent on exogenous arginine and pyrimidine, a phenotype previously defined as high-CO2-requiring (HCR) prototrophy. IC enrichment significantly decreased the amounts of the enzymes in the pyrimidine biosynthetic pathway encoded by the pyrR 1 BCAa 1 Ab 1 DFE operon, as demonstrated by proteomic analysis. Northern blot and reverse transcription-PCR experiments demonstrated that IC levels regulated pyr genes mainly at the level of transcription or RNA stability. Two putative PyrR regulators with 62% amino acid identity are present in the L. plantarum genome. PyrR1 is an RNA-binding protein that regulates the pyr genes in response to pyrimidine availability by a mechanism of transcriptional attenuation. In this work, the role of PyrR2 was investigated by allelic gene replacement. Unlike the pyrR 1 mutant, the ΔpyrR 2 strain acquired a demand for both pyrimidines and arginine unless bicarbonate or CO2 was present at high concentrations, which is known as an HCR phenotype. Analysis of the IC- and pyrimidine-mediated regulation in pyrR 1 and pyrR 2 mutants suggested that only PyrR2 positively regulates the expression levels of the pyr genes in response to IC levels but had no effect on pyrimidine-mediated repression. A model is proposed for the respective roles of PyrR1 and PyrR2 in the pyr regulon expression.
The hsp90 Chaperone Complex Regulates Intracellular Localization of the Dioxin Receptor

ABSTRACT The molecular chaperone complex hsp90-p23 interacts with the dioxin receptor, a ligand-dependent basic helix-loop-helix (bHLH)/Per-Arnt-Sim domain transcription factor. Whereas biochemical and genetic evidence indicates that hsp90 is important for maintenance of a high-affinity ligand binding conformation of the dioxin receptor, the role of hsp90-associated proteins in regulation of the dioxin receptor function remains unclear. Here we demonstrate that the integrity of the hsp90 complex characterized by the presence of the hsp90-associated cochaperone p23 and additional cochaperone proteins is important for regulation of the intracellular localization of the dioxin receptor by two mechanisms. First, in the absence of ligand, the dioxin receptor-hsp90 complex was associated with the immunophilin-like protein XAP2 to mediate cytoplasmic retention of the dioxin receptor. Second, upon exposure to ligand, the p23-associated hsp90 complex mediated interaction of the dioxin receptor with the nuclear import receptor protein pendulin and subsequent nuclear translocation of the receptor. Interestingly, these two modes of regulation target two distinct functional domains of the dioxin receptor. Whereas the nuclear localization signal-containing and hsp90-interacting bHLH domain of the receptor regulates ligand-dependent nuclear import, the interaction of the p23-hsp90-XAP2 complex with the ligand binding domain of the dioxin receptor was essential to mediate cytoplasmic retention of the ligand-free receptor form. In conclusion, these data suggest a novel role of the hsp90 molecular chaperone complex in regulation of the intracellular localization of the dioxin receptor.
Association between childhood trauma and physical disorders among adults in the United States

Background. The goal of this investigation was to determine the association between self-reported childhood trauma and physical disorders among adults in the United States. Method. Data were drawn from the National Comorbidity Survey (N=S877). Multiple logistic regression analyses were used to determine the associations between childhood physical abuse, sexual abuse, and childhood neglect and the likelihood of specific physical disorders among adults. Results. Childhood physical abuse, sexual abuse and neglect were associated with a statistically significantly increased risk of a wide range of physical illnesses during adulthood. After adjusting for demographic characteristics, lifetime anxiety and depressive disorders, alcohol and substance dependence, and all types of trauma: results showed that childhood physical abuse was associated with increased risk of lung disease (OR=1·5 (1·1, 2·2)), peptic ulcer (OR=1·5 (1·03, 2·2)) and arthritic disorders (OR=1·5 (1·1, 2·2)); childhood sexual abuse was associated with increased risk of cardiac disease (OR=3·7 (1·5, 9·4)); and childhood neglect was associated with increased risk of diabetes (OR=2·2 (1·1, 4·4)) and autoimmune disorders (OR=4·4 (1·7, 11·6)). Conclusions. Consistent with previous work, these results suggest that self-reported childhood trauma is associated with increased risk of a range of physical illnesses during adulthood. Future research that includes replication of these findings using prospectively assessed physical and mental disorders with objectively measured biological data using a longitudinal design, including other known risk factors for these diseases and more detailed information on specific forms of abuse, is needed to understand the potential mechanisms of these links.
Transfer and persistence of viral antibody-producing cells in bone marrow transplantation.

Antiviral humoral reactivity was studied after bone marrow transplantation. Antiviral IgG--reflecting the presence of functional B cells--was found for a substantial period after transplantation. However, most patients unexpectedly stopped producing antibody after an extended period of observation (i.e., for more than three months and up to as long as 12 months). This cessation was noted whether the viral reactivity involved was of donor or recipient origin. The transferred viral antibody-producing cells thus usually persisted for only a moderate length of time and seemed to have a finite life span. The findings indicate that donor and recipient memory cells are susceptible to the conditioning regimen or to the treatment that follows transplantation. In a few cases transferred immunity of long duration was seen; this finding indicated the occasional engraftment of memory cells.
Treatment of acute posttraumatic stress disorder with brief cognitive behavioral therapy: a randomized controlled trial.

OBJECTIVE The purpose of this study was to evaluate the efficacy of brief cognitive behavioral therapy for patients with acute posttraumatic stress disorder (PTSD) resulting from various types of psychological trauma. METHOD The authors randomly assigned 143 patients with acute PTSD (irrespective of the time criterion), within 3 months after experiencing a traumatic incident, to either brief cognitive behavioral therapy (N=79) or a waiting list comparison group (N=64). Cognitive behavioral therapy consisted of four weekly sessions containing education, relaxation exercises, imaginal exposure, in vivo exposure, and cognitive restructuring. Main outcome measure was PTSD score measured by structured interview; secondary outcomes were anxiety and depression measured by questionnaire. Assessments took place before the intervention and 1 week and 4 months after the intervention. RESULTS Symptoms of PTSD, anxiety, and depression decreased in both groups over time. One week after the intervention, the cognitive behavioral therapy group had significantly fewer symptoms of PTSD than the comparison group, but this difference was smaller and no longer significant 4 months after the intervention. Similar results were found for anxiety and depression scores. Subgroup analyses showed that cognitive behavioral therapy led to significantly lower PTSD scores at 4 months in patients with baseline comorbid major depression and in patients who were included within the first month after the traumatic incident both at 1 week and at 4 months. CONCLUSIONS Brief early cognitive behavioral therapy accelerated recovery from symptoms of acute PTSD but did not influence long-term results. Brief early cognitive behavioral therapy showed enhanced efficacy in patients with baseline comorbid depression and patients who were included within 1 month after their traumatic experience.
Delayed Inflammatory Response to Primary Pneumonic Plague Occurs in Both Outbred and Inbred Mice

ABSTRACT Yersinia pestis is the causative agent of plague, a disease that can manifest as either bubonic or pneumonic plague. An interesting feature of plague is that it is a rapidly progressive disease, suggesting that Y. pestis either evades and/or suppresses the innate immune response to infection. Therefore, the early host response during the course of primary pneumonic plague was investigated in two mouse strains, the outbred strain CD1 and the inbred strain C57BL/6. A comparative analysis of the course of disease in these two strains of mice indicated that they are susceptible to intranasal Y. pestis CO92 infection and have similar 50% lethal doses and kinetics of infection with respect to colonization of the lung, liver, and spleen. Significantly, in both strains of mice, robust neutrophil recruitment to the lungs was not observed until 48 h after infection, suggesting that there was a delay in inflammatory cell recruitment to the site of infection. In addition, proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha, gamma interferon, IL-12p70, monocyte chemoattractant protein 1) and chemokines (KC, MIP-2) in the bronchoalveolar lavage fluids were not readily detected until 48 h after infection, which coincided with the increase in polymorphonuclear leukocyte (PMN) recruitment to the lungs. In comparison, CD1 mice with gram-negative pneumonia caused by Klebsiella pneumoniae exhibited strong inflammatory responses early in infection, with PMNs comprising the majority of the cells in the bronchoalveolar lavage fluid 24 h postinfection, indicating that PMN recruitment to the lungs could occur earlier in this infection than in Y. pestis infection. Together, our results indicate that there is a delay in the recruitment of neutrophils to the lungs in the mouse model of primary plague pneumonia that correlates with delayed expression of proinflammatory cytokines and chemokines in both outbred and inbred mice.
Changes in interstitial adenosine during hypoxia: relationship to oxygen supply:demand imbalance, and effects of adenosine deaminase.

OBJECTIVE The aim was to determine the changes in coronary blood flow and intramyocardial interstitial fluid (ISF) adenosine and adenosine metabolites during systemic hypoxia, and to evaluate (1) whether the increase in ISF adenosine during hypoxia is augmented if the hypoxic hyperaemia is prevented, and (2) the effects of adenosine deaminase on ISF adenosine and coronary blood flow during sustained hypoxia. METHODS Anaesthetised dogs were instrumented with a flow probe around the left anterior descending coronary artery to measure coronary blood flow and with a microdialysis probe in the myocardium perfused by this artery to sample intramyocardial ISF. Dialysate purine metabolite levels were used as indices of ISF levels. Systemic hypoxia was induced by a reduction in the FIO2. RESULTS Acute systemic hypoxia (PaO2 approximately 3.9 kPa) resulted in a 60% increase in dialysate adenosine, along with increases in dialysate levels of the adenosine metabolites inosine (74%), hypoxanthine (33%), and xanthine (32%). If the hypoxic hyperaemia was prevented, dialysate adenosine increased by 180% during hypoxia, and the increases in adenosine metabolites were augmented as well. During sustained hypoxia, intracoronary administration of adenosine deaminase decreased dialysate adenosine below prehypoxia levels, but did not alter the hypoxic hyperaemia. CONCLUSIONS While ISF adenosine is increased during acute systemic hypoxia and is increased in relation to the oxygen supply:demand imbalance, consistent with a role of adenosine in hypoxic hyperaemia in the heart, adenosine is not necessary for the maintenance of a sustained increase in coronary blood flow during hypoxia.
Pneumonia caused by oxacillin-resistant Staphylococcus aureus treated with glycopeptides*

Objective:To determine whether ventilator-associated pneumonia caused by oxacillin-resistant Staphylococcus aureus (VAP-ORSA) treated with glycopeptides is associated with an increased mortality rate. Design:Retrospective matched cohort study. Setting:Four intensive care units in teaching hospitals. Patients:Seventy-five patients were matched to 75 controls. Interventions:None. Measurements and Main Results:All adult intensive care unit patients with microbiologically documented VAP-ORSA were matched to intubated controls who did not develop VAP-ORSA, based on disease severity (Acute Physiology and Chronic Health Evaluation II score) at admission (±3 points), diagnostic category, and length of stay before pneumonia onset. Population characteristics and intensive care unit mortality rates of patients with VAP-ORSA and their controls without pneumonia were compared. Attributable mortality was determined by subtracting the crude mortality rate of controls from the crude mortality rate of VAP-ORSA patients. Thirty-six of the 75 matched VAP-ORSA patients died, representing a crude mortality rate of 48%, whereas 19 of the 75 controls died, a crude mortality rate of 25.3% (p < .01). Excess mortality was estimated to be 22.7% (95% confidence interval, 2.4–42.9%). Median length of intensive care unit stay in the surviving pairs was 33 days (interquartile range, 25–75%: 25-45 days) for VAP-ORSA patients and 21 days (interquartile range, 25–75%: 15–34.75 days) days for controls (p = .054). Conclusions:Despite appropriate glycopeptide therapy, there is an increased attributable mortality for pneumonia by ORSA, after careful adjustment for disease severity and diagnostic category.
[Drug prescription for hospitalized pediatric patients: how can the quality be evaluated?].

BACKGROUND Pediatric patients called "therapeutic orphans" are usually excluded from clinical trials for development of new drugs, which, sometimes, are used empirically. This study evaluates the prescriptions for pediatric inpatients, and proposes criteria for evaluation of the quality of the prescriptions. METHODS The hospital pharmacist determined the prevalence of drug prescription in five pediatric wards. One day collection of all prescriptions for pediatric inpatients was performed in March, April, May and June 1999, and the data were jointly analyzed. Six criteria were proposed for quality evaluation of the drug prescriptions. The drugs were classified according to the ATC classification index. RESULTS The prescriptions of a total of 322 patients were collected in the four collection days. The three most common diagnoses were: pneumonia 40.4%, meningitis and meningococcemia 6%, diarrhea and dehydration 6%. The three most prescribed therapeutic classes were: nervous system (N ) 109%, general antiinfectives for systemic use ( J ) 81.9% and respiratory system ( R ) 69,0%. The three most prescribed drugs were: metamizole 88.3%, fenoterol 30.7% and penicillin G 25.0%. The quality evaluation showed 1. an excessive use of the intravenous route, 2. appropriate dose schedule for drugs with narrow therapeutic index, 3. no therapeutic duplication, 4. prescription of unapproved and off-label drugs, 5. frequent potential adverse drug interactions, and 6. prescription of drugs not in the therapeutic formulary of the hospital. CONCLUSION Very simple measures can improve the quality of the health care of pediatric inpatients as inclusion of adequate drug presentations in the hospital formulary, and a careful evaluation of the need of the intravenous route. This study also shows the hospital pharmacists acting as part of the multidisciplinary health care team.
Is the Internet gaming‐addicted brain close to be in a pathological state?

Internet gaming addiction (IGA) is becoming a common and widespread mental health concern. Although IGA induces a variety of negative psychosocial consequences, it is yet ambiguous whether the brain addicted to Internet gaming is considered to be in a pathological state. We investigated IGA‐induced abnormalities of the brain specifically from the network perspective and qualitatively assessed whether the Internet gaming‐addicted brain is in a state similar to the pathological brain. Topological properties of brain functional networks were examined by applying a graph‐theoretical approach to analyzing functional magnetic resonance imaging data acquired during a resting state in 19 IGA adolescents and 20 age‐matched healthy controls. We compared functional distance‐based measures, global and local efficiency of resting state brain functional networks between the two groups to assess how the IGA subjects' brain was topologically altered from the controls' brain. The IGA subjects had severer impulsiveness and their brain functional networks showed higher global efficiency and lower local efficiency relative to the controls. These topological differences suggest that IGA induced brain functional networks to shift toward the random topological architecture, as exhibited in other pathological states. Furthermore, for the IGA subjects, the topological alterations were specifically attributable to interregional connections incident on the frontal region, and the degree of impulsiveness was associated with the topological alterations over the frontolimbic connections. The current findings lend support to the proposition that the Internet gaming‐addicted brain could be in the state similar to pathological states in terms of topological characteristics of brain functional networks.
Salmonella typhi stimulation of human intestinal epithelial cells induces secretion of epithelial cell-derived interleukin-6

Interleukin 6 (IL-6) is a multifunctional cytokine that has been shown to be associated with both systemic and tissue-specific responses within the host. Moreover, IL-6 is produced by both lymphoid and nonlymphoid cells and has been identified as a growth-inducing, growth-inhibiting, and differentiation-inducing factor for these cells. Recent studies of uropathogenic and upper respiratory pathogens have suggested that epithelial cell-derived IL-6 plays a role in mucosal host-parasite interactions. Since many mucosal enteric pathogens enter the host through the epithelial cells of the distal small intestine, a role for intestinal epithelial cell-derived IL-6 in the initial interaction between bacteria and host might also be predicted. However, no studies to date have determined whether the interaction of any bacteria with the epithelial cells that line the small intestine of the host can induce IL-6. To address this issue, we have established an in vitro model to evaluate the capacity of the gram-negative bacterium Salmonella typhi to induce IL-6 in the small intestine epithelial cell line Int407 and in other intestinal epithelial cell lines. The results demonstrate that both wild-type and live, attenuated S. typhi vaccine strains induce small and large intestine epithelial cells to secrete IL-6, and kinetic analysis suggests that IL-6 may be one of the earliest responses following adherence and invasion of enteric organisms. Thus, these studies suggest a physiologic role for epithelial cell-derived IL-6 in the initial interactions between host and bacterium in the small intestine.
Properties of a non‐tumorigenic human cervical keratinocyte cell line

A human cervical keratinocyte cell line, W12, has been initiated from a low‐grade cervical lesion histologically diagnosed as CIN I. This cell line has, to date, undergone over 300 generations in vitro with an average doubling time of 30 hr: an aneuploid karyotype has developed with progressive in vitro growth. W12 contains HPV16 DNA present at approximately 100 copies and the state of the viral DNA over a number of passages has been examined. The HPV13 DNA is stably maintained at high copy number over several passages and restriction enzyme analysis together with electrophoresis of uncleaved viral DNA indicate that it is present predominantly as the episomal molecule. W12 cells exhibit a typical keratinocyte morphology and, when transplanted into the flank of the nude mouse, form an epithelial lesion with the histological features of CIN I/II.