Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: Roles of transforming growth factor (TGF)‐β and bone morphogenetic protein (BMP)

Endothelial‐mesenchymal transformation (EMT) is a critical event in the generation of the endocardial cushion, the primordia of the valves and septa of the adult heart. This embryonic phenomenon occurs in the outflow tract (OT) and atrioventricular (AV) canal of the embryonic heart in a spatiotemporally restricted manner, and is initiated by putative myocardially derived inductive signals (adherons) which are transferred to the endocardium across the cardiac jelly. Abnormal development of endocardial cushion tissue is linked to many congenital heart diseases. At the onset of EMT in chick cardiogenesis, transforming growth factor (TGFβ)‐3 is expressed in transforming endothelial and invading mesenchymal cells, while bone morphogenetic protein (BMP)‐2 is expressed in the subjacent myocardium. Three‐dimensional collagen gel culture experiments of the AV endocardium show that 1) myocardially derived inductive signals upregulate the expression of AV endothelial TGFβ3 at the onset of EMT, 2) TGFβ3 needs to be expressed by these endothelial cells to trigger the initial phenotypic changes of EMT, and 3) myocardial BMP2 acts synergistically with TGFβ3 in the initiation of EMT. Anat Rec 258:119–127, 2000. © 2000 Wiley‐Liss, Inc.
On the Mechanism of Hepatocarcinogenesis of Benzodiazepines: Evidence that Diazepam and Oxazepam are CYP2B Inducers in Rats, and both CYP2B and CYP4A Inducers in Mice

The aim of this study was to evaluate diazepam and oxazepam as cytochrome P450 inducers at doses previously shown to cause liver tumors in mice but not rats. In rats, diazepam and oxazepam induced CYP2B, and were as effective as phenobarbital despite lacking phenobarbital's tumor-promoting effect in rats. In mice, diazepam and oxazepam induced both CYP2B and CYP4A at dietary doses associated with liver tumor formation. It remains to be determined why diazepam and oxazepam induce CYP4A in mice but not rats and whether this difference accounts for the apparent species difference in the tumor-promoting activity of diazepam and oxazepam.
Foreclosures and Health in a Neighborhood Context

Recent systematic reviews link foreclosure to worse health at both the individual and population levels. In this issue of the Journal , Downing et al. ( Am J Epidemiol . 2017;185(6):429 – 435) add to what is known about foreclosure and health by examining annual measures of glycemic control in relation to local foreclosure activity. They provided evidence that between 2007 and 2010, glycemic control was not associated with rates of completed foreclosure among a continuously insured managed-care population of persons with type 2 diabetes living in 9 California counties. In this commentary, I consider 5 possible interpretations of the null results: 1) foreclosures do not affect health in general, 2) glycated hemoglobin is insensitive to local foreclosure activity, 3) the presence of real estate owned foreclosures (rather than the competed foreclosure rate) affects health, 4) an integrated health-care delivery system buffers patients from the effects of the foreclosure crisis, and 5) community conditions and responses to the foreclosure crisis buffer patients from the effects of the foreclosure crisis. I close by arguing that research on the contextual effects of foreclosure on health should continue despite the ongoing recovery of the housing market.
WhiteMatter Structural Differences in Young ChildrenWith Type 1 Diabetes : A Diffusion Tensor Imaging Study

RESULTSdCompared with healthy controls, children with type 1 diabetes had lower axial diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions. There were no significant differences between groups in fractional anisotropy and radial diffusivity (RD). Within the diabetes group, there was a significant, positive correlation between time-weighted HbA1c and RD (P = 0.028). A higher, time-weighted HbA1c value was significantly correlated with lower overall intellectual functioning measured by the full-scale intelligence quotient (P = 0.03).
Atypical Nonketotic Hyperglycinemia With Normal Cerebrospinal Fluid to Plasma Glycine Ratio

The diagnosis of nonketotic hyperglycinemia is considered to depend upon the presence of increased cerebrospinal fluid glycine and an increased cerebrospinal fluid to plasma glycine ratio. We studied two siblings who have the neurologic and peripheral biochemical features of the atypical variant of nonketotic hyperglycinemia but have normal cerebrospinal fluid glycine and cerebrospinal fluid to plasma glycine ratios. The proband had reduced liver glycine cleavage system activity of 17% and 21% of mean normal values, confirmed in two independent laboratories. Her lymphoblast glycine cleavage system activity was normal. Nonketotic hyperglycinemia can be present in the absence of increased cerebrospinal fluid glycine. Measurement of liver glycine cleavage system activity is indicated when nonketotic hyperglycinemia is suggested by clinical features and peripheral glycine levels but cerebrospinal fluid glycine is normal. (J Child Neurol 1999;14:464-467).
SOCIOECONOMIC COSTS OF RHEUMATIC DISEASES

Objectives: To study the socioeconomic impact of rheumatic illness in Sweden and to discuss the consequences for technology assessment studies. Methods: A cost-of-illness study based on data from official statistics and treatment studies. Results: The total socioeconomic cost was 52 billion Swedish kronor (SEK) in 1994. The imbalance between direct (10% of total) and indirect costs (90effectiveness of the healthcare sector, the need for new treatment methods, appropriate information systems, and technology assessment studies as well as the institutional arrangements for rehabilitation and basic medical research. Conclusions: A discussion of solutions for financial cooperation between county councils and regional social insurance offices should be considered. The new biotechnological pharmaceuticals will increase the cost for drugs in health care about 20 times, but the total socioeconomic cost for society may remain at the same level due to a decrease of inpatient costs and indirect costs for loss of production as well as a decrease of transfer payments from social insurance. It is unavoidable that the new pharmaceuticals require priority discussions and active resource allocation in health care and in other sectors of society.
Malononitrilamides synergistically prevent acute and treat ongoing skin allograft rejection with cyclosporine

Abstract The low molecular weight malononitrilamides (MNAs), a new class of immunosuppressive agents, belong to the derivatives of leflunomide's active metabolite, A771726. They have been shown to bind specifically to dehydroorotate dehydrogenase and inhibit de novo pyrimidine biosynthesis, thereby blocking T- and B-cell proliferation and strongly suppressing IgM and IgG antibody production. Here we evaluated their efficacy together with cyclosporine (CyA) in rat skin allotransplantation models, using different strain combinations. Monotherapy of transplanted animals in these models with the MNAs HMR 1279 and HMR 1715 resulted in a significant and dose-dependent prolongation of the graft survival time. Even a short-term application showed efficacy in the prevention of acute rejection. The MNAs were also effective when treatment was started at the time of expected rejection crisis, demonstrating strong therapeutic activity to reverse ongoing acute rejection, whereas CyA was ineffective for the treatment of ongoing allograft rejection episodes. Combination therapy of MNAs with CyA proved to be very effective for the prevention of acute skin graft rejection. Interestingly, whereas CyA alone was unable to treat ongoing acute rejection episodes, comedication of MNAs and CyA, even after a short-term application, was synergistically effective and significantly suppressed ongoing allogeneic skin graft rejection. These results demonstrate that MNAs are potent and well tolerated immunosuppressants with a potential comparable to that of CyA, but they are superior to CyA in their ability to reverse acute rejection episodes. They represent powerful rescue drugs and demonstrate synergistic activity with CyA to prevent acute and treat ongoing skin allograft rejection.
The concurrent use of touch and mid-air gestures or floor mat interaction on a public display

This paper investigates a novel approach to simultaneously use the qualities of touch and mid-air gestures or floor mat interaction on a public display. We demonstrate that although the concurrent use of multiple interaction modalities appeared functionally possible and has the potential to augment a single display with both personal and public functionalities, it is hampered by issues relating to display and interaction blindness, in addition to social discomfort and what we propose to name affordance blindness. We describe this blindness as the inability to understand the interaction modalities of a public display. Overall, passers-by tend to assume that a public display only supports a single interaction modality, an issue that is hard to overcome with ergonomic or visual interventions, or via physical curiosity objects. Although user engagement was relatively limited, we believe that our qualitative results highlight several crucial design and usability aspects when designing multi-modal, interactive public displays. Furthermore, this study demonstrates that previous knowledge on public display interaction cannot be simply ported to other contexts, and that more diverse content-types or contextual use cases should be evaluated "in-the-wild" to attain more generalizable insights.
A new solar to hydrogen conversion system with high efficiency and flexibility

Solar-to-hydrogen energy conversion is a promising technology because it enables high-capacity, long-term storage of solar energy. We propose a new highly efficient solar-to-hydrogen conversion system consisting of multiple converter-electrolyzer sets connected in parallel to a photovoltaic (PV) array. This system is flexible to apply to various PV configurations. One-day simulations based on measured PV and electrolyzer characteristics demonstrate very high maximum power point tracking (MPPT) efficiency (higher than 99.9%) and average power conversion efficiency (94.0%) on a clear sunny day. Annual energy production is expected to increase by 8.5%-point compared with a single converter system using one of the best commercial converter. The key elements of the high efficiency are the new system topology, a specially designed phase-shift full-bridge converter and a control method “P&O with converter scoring” algorithm.
Examining the Relationship Between Bone Mineral Density and Fracture Risk Reduction During Pharmacologic Treatment of Osteoporosis

Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes the patient to an increased risk for fracture. Elements of bone strength include bone mineralization, architecture, turnover, size, and bone mineral density (BMD). Measurement of BMD is the most readily available, noninvasive method for assessing osteoporotic fracture risk and is used by the World Health Organization for diagnostic purposes. Because low BMD is predictive of increased fracture risk, it was believed that changes in BMD during pharmacologic therapy for osteoporosis would strongly predict observed fracture risk reductions. We examined the relationship between changes in BMD and reduction in fracture risk during pharmacologic therapy in postmenopausal women with osteoporosis. The correlation between BMD increases and fracture risk reduction during treatment is not consistent; larger increases in BMD do not necessarily correlate with greater reductions in fracture risk. Multiple factors, in addition to BMD, appear to contribute to the increased bone strength and decreased fracture risk achieved with approved drug therapies for osteoporosis. Until the exact relationship of these factors is fully understood, clinicians should continue to evaluate drug efficacy for osteoporosis based on the fracture risk reductions from well‐designed clinical trials.
A specific sequence of stimulation is required to induce synthesis of the antimicrobial molecule nitric oxide by mouse macrophages

Nitric oxide production by macrophages required either simultaneous or sequential exposure to gamma interferon and lipopolysaccharide; exposure to lipopolysaccharide followed by exposure to gamma interferon gave little response. The apparently evanescent nature of the lipopolysaccharide signal, necessitating persistent stimulation, could be essential to down-regulating nitric oxide production after bacteria are cleared in vivo.
Guidelines 2000 for colon and rectal cancer surgery.

BACKGROUND Oncologic resection techniques affect outcome for colon cancer and rectal cancer, but standardized guidelines have not been adopted. The National Cancer Institute sponsored a panel of experts to systematically review current literature and to draft guidelines that provide uniform definitions, principles, and practices. METHODS Methods were similar to those described by the American Society of Clinical Oncology in developing practice guidelines. Experts representing oncology and surgery met to review current literature on oncologic resection techniques for level of evidence (I-V, where I is the best evidence and V is the least compelling) and grade of recommendation (A-D, where A is based on the best evidence and D is based on the weakest evidence). Initial guidelines were drafted, reviewed, and accepted by consensus. RESULTS For the following seven factors, the level of evidence was II, III, or IV, and the findings were generally consistent (grade B): anatomic definition of colon versus rectum, tumor-node-metastasis staging, radial margins, adjuvant R0 stage, inadvertent rectal perforation, distal and proximal rectal margins, and en bloc resection of adherent tumors. For another seven factors, the level of evidence was II, III, or IV, but findings were inconsistent (grade C): laparoscopic colectomy; colon lymphadenectomy; level of proximal vessel ligation, mesorectal excision, and extended lateral pelvic lymph node dissection (all three for rectal cancer); no-touch technique; and bowel washout. For the other four factors, there was little or no systematic empirical evidence (grade D): abdominal exploration, oophorectomy, extent of colon resection, and total length of rectum resected. CONCLUSIONS The panel reports surgical guidelines and definitions based on the best available evidence. The availability of more standardized information in the future should allow for more grade A recommendations.
Pregnancy and early‐stage melanoma

Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the long‐term effect of pregnancy on disease progression in women with Stage I–II melanoma.
Evaluation of secondary haemostasis in canine leishmaniasis

Secondary haemostasis was evaluated in 26 dogs with leishmaniasis and 10 normal dogs by measurements of modified one-stage prothrombin time (m-OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration and fibrin degradation products. There were no significant differences between the groups in the m-OSPT, fibrinogen concentration, or levels of fibrin degradation products. The AM was significantly (P=0.006) longer in the infected dogs than in the control group, and in infected dogs with alanine aminotransferase (ALT) activities >50 U/litre. There was a significant linear regression between ALT and AM. Thrombin time was significantly (P=0.003) longer in the infected dogs than in the normal dogs. There were no significant differences between the thrombin times of sick dogs with different levels of creatinine or activities of ALT, or between male and female dogs, whether diseased or normal.
Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double‐blind, randomized, controlled trial

A 12‐month double‐blind sham‐surgery–controlled trial assessing adeno‐associated virus type 2 (AAV2)‐neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2‐neurturin delivered to putamen and substantia nigra.
Cortisol level decreases natural killer cell activity among women exposed to aircraft noise

One of the impacts of exposure to noise is stress. Natural killer (NK) cells are one of the leukocyte subsets that are responsive to physiological and psychological stress. The objective of the present research was to determine the relationship between cortisol levels and NK cell activity among women with aircraft noise stress in the area of Adi Sumarmo Airport, Solo. This study was an analytical survey with a cross sectional design. The number of subjects was 39, who were divided into 3 groups of 13 subjects each. Groups 1 to 3 were exposed to noise levels of 92.29 dB, 71.79 dB and 52.17 dB, respectively. The sample was taken using simple random sampling. The data were analyzed by Pearson correlation test and Anova followed by post hoc test using LSD test. The Anova test showed that there were significant differences in circulating cortisol levels among all groups (p = 0.018). The Pearson correlation test showed that there was a positive association between circulating cortisol levels and the number of NK cells (r = 0.547; p< 0.05) and a negative association between circulating cortisol levels and NK cell activity (r = - 0.578; p < 0.05). This study indicated that cortisol levels decreased NK cell activity among women with exposure to aircraft noise. Women who experienced aircraft noise stress showed increased cortisol levels and decreased NK cells activity.
Immunity and Tolerance to Aspergillus Involve Functionally Distinct Regulatory T Cells and Tryptophan Catabolism1

The inherent resistance to diseases caused by Aspergillus fumigatus suggests the occurrence of regulatory mechanisms that provide the host with adequate defense without necessarily eliminating the fungus or causing unacceptable levels of host damage. In this study, we show that a division of labor occurs between functionally distinct regulatory T cells (Treg) that are coordinately activated by a CD28/B-7-dependent costimulatory pathway after exposure of mice to Aspergillus conidia. Early in infection, inflammation is controlled by the expansion, activation and local recruitment of CD4+CD25+ Treg capable of suppressing neutrophils through the combined actions of IL-10 and CTLA-4 on indoleamine 2,3-dioxygenase. The levels of IFN-γ produced in this early phase set the subsequent adaptive stage by conditioning the indoleamine 2,3-dioxygenase-dependent tolerogenic program of dendritic cells and the subsequent activation and expansion of tolerogenic Treg, which produce IL-10 and TGF-β, inhibit Th2 cells, and prevent allergy to the fungus. The coordinate activation of Treg may, however, be subverted by the fungus, as germinating conidia are capable of interfering with anti-inflammatory and tolerogenic Treg programs. Thus, regulation is an essential component of the host response in infection and allergy to the fungus, and its manipulation may allow the pathogen to overcome host resistance and promote disease.
Multicentric Osteosarcoma, Rothmund‐Thomson Syndrome, and Secondary Nasopharyngeal Non‐Hodgkin's Lymphoma: A Case Report and Review of the Literature

Purpose: Rothmund-Thomson syndrome (RTS) is an autosomal recessive disease characterized by poikiloderma. photosensitivity. skeletal deformities, and other changes. It is also associated with an increased risk of malignancies, including osteosarcoma. Sixteen previous cases of RTS and osteosarcoma have been reported. Patient: A patient with RTS in whom multicentric osteosarcoma developed is described. After surgery and chemotherapy, a secondary malignant neoplasm (SMN) developed consistent with nasopharyngeal non-Hodgkin's lymphoma. Results: The patient was treated with anli-CD20 monoclonal antibody and is in complete remission. Conclusion: This is the first report of a patient with RTS treated for osteosarcoma in whom a SMN developed. Potential factors involved in this SMN include genetic predisposition and previous chemotherapy.
Prevalence of sleep-disordered breathing in ages 40-64 years: a population-based survey.

Previous research has offered widely varying prevalence estimates for sleep apnea in the population, leaving uncertain which breathing patterns are abnormal. To explore the distribution of sleep apnea in the population and its co-morbidities, random telephone dialing was used between 1990 and 1994 to recruit subjects for a prevalence survey of sleep-disordered breathing in San Diego adults. Events from which blood oxygen desaturations > or = 4% resulted were monitored with home recording instruments, usually for three consecutive nights. Among 190 women ages 40-64 years, a median of 4.3 desaturation events per hour of sleep were observed. A higher median of 6.7 events per hour was observed among 165 men. Frequencies were much higher among members of minority groups, leading to a standard estimate that 16.3% of U.S. Hispanics and racial minorities have > or = 20 events/hour as compared to 4.9% of non-Hispanic Whites ages 40-64. Obesity indicated by body-mass index was the most important demographic predictor of sleep-disordered breathing, followed by age, male gender, and ethnicity. Quality of well-being was not significantly impaired in subjects with more respiratory events; however, there was some increase in blood pressure and wake-within-sleep associated with sleep-disordered breathing. This survey indicates that sleep-disordered breathing is more common, especially among minorities, than had been previously believed, but less co-morbidity may be associated.
Renal neurohormonal and vascular responses to dynamic exercise in humans.

Effects of graded supine dynamic exercise (30, 60, and 80-90% of maximal physical capacity, i.e., work loads of 69, 132, and 188 W) on renal vascular resistance (RVR); renal sympathetic nerve activity [assessed by the renal venous overflow of norepinephrine (NE)]; renal overflows of dopamine (DA), immunoreactive neuropeptide Y (NPY-LI), and renin; as well as plasma concentrations of angiotensin-(1-8)-octapeptide (ANG II) were evaluated in eight healthy male volunteers. Exercise evoked stimulus-dependent and marked elevations of RVR, arterial NE, epinephrine (Epi), and DA. RVR increased by 140% and the renal overflows of NE and DA increased by 1,331 and 179%, respectively, at 188 W. A net removal of NPY-LI at rest turned into a small net renal overflow, which correlated with increases in RVR at 188 W. Increases in renin release (+1,200% at 188 W) correlated with increases in renal NE and DA overflows and with arterial Epi levels. Arterial ANG II levels increased stimulus dependently (by 264% at 188 W) and correlated more closely with increases in RVR than did other variables. Thus dynamic exercise is a potent stimulus for renal nerve activation in humans, and renal sympathetic nerve activity may contribute to increased RVR both directly (NE and, at exhaustive work loads, possibly NPY) and indirectly (via renin-mediated ANG II formation).