Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma Mineralocorticoids, Glucocorticoids, and Progestins in Premature Infants: Longitudinal Study during the First Week of Life

ABSTRACT: Plasma levels of aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyproges-terone, 11-deoxycortisol, cortisol, and cortisone were measured simultaneously by a micromethod of multisteroid analysis in eight vaginally delivered premature infants (PI) of 33–36 wk gestation with uneventful peri- and postnatal course. Mean concentrations (ng/ml) in umbilical arterial and in peripheral venous or capillary plasma sampled longitudinally at age 2 h to 7 days were compared with the same kind of data obtained from a group of 12 term infants (TI) who served as controls. Mean aldosterone was two to five times higher in PI than in TI (umbilical artery, 2 h to 7 days; p < 0.05), whereas 11-deoxycorticosterone was lower in PI from 2 h (p < 0.01) until 7 days (NS). Corticosterone was significantly higher in PI than TI at 6 and 24 h after birth, whereas cortisol was slightly lower (NS) in PI in umbilical artery and 2 h after birth, but higher (p < 0.02) at 6 h, showing less variation in PI than in TI. 17-Hydroxyprogesterone levels in PI were two to three times higher (p < 0.02) during 6 h until 7 days after birth. The data suggest that PI are able to maintain high aldosterone levels in the early neonatal period. Higher levels of the active glucocorticoids (cortisol and corticosterone) seen after delivery point to a more stressful extrauterine adaptation of PI. Furthermore, the data demonstrate that the adrenal cortex is fully functioning in premature infants (33–36 wk gestation) as well as in term infants.
End-systolic pressure-volume relationship and intracellular control of contraction.

The left ventricular (LV) pressure-volume relationship and the effect of ejection on pressure generation are predicted theoretically based on the intracellular control mechanisms. The control of contraction is described based on coupling calcium kinetics and cross-bridge cycling. The analysis of published skinned and intact cardiac muscle data suggests two feedback control loops: 1) a positive cooperative mechanism that determines the force-length relationship, the length dependence calcium sensitivity of the contractile filaments, and the related Frank Starling law; and 2) a negative mechanical feedback that determines the force-velocity relationship and the generated power. The interplay between these two feedback mechanisms explains the wide spectrum of phenomena associated with the end-systolic pressure-volume relationship (ESPVR); it provides an explanation for the "shortening deactivation" and for the recent observations of the positive effect of ejection on the ESPVR, i.e., the increase of the end-systolic pressure of the ejecting beat over the pressure of the isovolumic beat at the same end-systolic volume. Furthermore, the analysis suggests that the LV contractility depends on the balance between the two intracellular mechanisms and that the effect of loading conditions is determined through these intracellular mechanisms.
The impact of service quality, customer satisfaction and loyalty in the restaurant industry: Moderating effect of perceived value

This study contributes to a conceptual model that, reflecting the mediating role of customer satisfaction and the moderating role of perceived value, indicates the effect of service quality on customer loyalty in the restaurant industry. The analysis confirms that customer satisfaction is positively influenced by service quality, whereas customer loyalty is positively influenced by customer satisfaction. Furthermore, customer loyalty is indirectly influenced by service quality through customer satisfaction. Finally, other key finding is the relationship between customer satisfaction and customer loyalty, which is stronger for customers who perceive high value than for those who perceive low value. According to the findings, the implications and future research directions are provided.
Demographic, clinical and therapeutic findings in a monocentric cohort of adult patients with suspected PFAPA syndrome.

OBJECTIVES Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a non-Mendelian autoinflammatory disorder until now considered to be specifically limited to paediatric age. Recently, an increasing number of reports seems to suggest that PFAPA syndrome, diagnosed by the Marshall criteria revised by Thomas et al., can also affect adults. METHODS The Marshall/Thomas criteria have been applied to 989 adult patients presenting for recurrent fever episodes: all patients enrolled were reviewed for demographic, clinical, and therapeutic data. Infectious, neoplastic, autoimmune and other autoinflammatory diseases were ruled out. RESULTS We identified 30 adult patients (19 males, 11 females) with a suspected PFAPA syndrome: their mean age at disease onset was 33.75±14.01 years, mean age at diagnosis 39.1±14.39 years, and mean body temperature peak 39.5±0.7°C. In addition, the mean frequency of febrile episodes was 11.58±8.97 per year. More precisely, patients complained of pharyngitis (77%), cervical adenitis (73%), asthenia (63%), arthralgia (67%), oral aphthosis (50%), myalgia (54%), cephalalgia (43%), abdominal pain (27%), nausea/vomiting (17%), periorbital pain (17%), and arthritis (10%). Six out of 30 (20%) patients had suffered from PFAPA syndrome also during childhood, and the disease had reappeared in adulthood. CONCLUSIONS We provide the largest monocentric cohort of patients diagnosed with a suspected PFAPA syndrome in adulthood confirming that this syndrome can occur also during adulthood; moreover, due to the medical history of our patients and based on our experience, PFAPA syndrome might relapse during adulthood after a temporary remission reached in the course of paediatric age.
Lessons learned from HIV pathogenesis and therapy: implications for better management of cytomegalovirus disease.

AIM To review how developments in virological quantitation technology have altered our understanding of the pathogenesis of HIV infection, and the way in which we treat the disease, and to consider how we may apply this type of knowledge to improve the management of cytomegalovirus (CMV) infection. HIV PATHOGENESIS HIV can no longer be regarded as the cause of a chronic, latent infection but rather as one that is active from the time of initial infection. The destruction of the immune system begins almost immediately after the primary infection is established. Throughout the course of the disease there is a constant war being waged between the rapidly replicating virus and the host's immune system. UTILITY OF MEASUREMENT OF VIRAL LOAD Viral load has been found to be a reliable and discriminating marker for predicting prognosis in HIV disease and for the evaluation of anti-HIV therapies. IMPLICATIONS FOR CYTOMEGALOVIRUS INFECTION AND DISEASE Unlike HIV, CMV is a truly latent infection with periods of active, detectable viral replication as well as quiescence. CMV DNA quantitation (CMV viral load), primarily by polymerase chain reaction can be used to determine when the infection becomes active in order to decide whether primary prophylaxis or pre-emptive therapy should be given. In this manner CMV viral load quantitation has considerable utility for monitoring the pathogenesis and type of treatment necessary for CMV infection in patients with AIDS.
Transcriptional Analysis of Quiescent and Proliferating CD34+ Human Hemopoietic Cells from Normal and Chronic Myeloid Leukemia Sources

Quiescent and dividing hemopoietic stem cells (HSC) display marked differences in their ability to move between the peripheral circulation and the bone marrow. Specifically, long‐term engraftment potential predominantly resides in the quiescent HSC subfraction, and G‐CSF mobilization results in the preferential accumulation of quiescent HSC in the periphery. In contrast, stem cells from chronic myeloid leukemia (CML) patients display a constitutive presence in the circulation. To understand the molecular basis for this, we have used microarray technology to analyze the transcriptional differences between dividing and quiescent, normal, and CML‐derived CD34+ cells. Our data show a remarkable transcriptional similarity between normal and CML dividing cells, suggesting that the effects of BCR‐ABL on the CD34+ cell transcriptome are more limited than previously thought. In addition, we show that quiescent CML cells are more similar to their dividing counterparts than quiescent normal cells are to theirs. We also show these transcriptional differences to be reflected in the altered proliferative activity of normal and CML CD34+ cells. Of the most interest is that the major class of genes that is more abundant in the quiescent cells compared with the dividing cells encodes members of the chemokine family. We propose a role for chemokines expressed by quiescent HSC in the orchestration of CD34+ cell mobilization.
Mutation of a Single Conserved Tryptophan in Multidrug Resistance Protein 1 (MRP1/ABCC1) Results in Loss of Drug Resistance and Selective Loss of Organic Anion Transport*

Multidrug resistance protein 1 (MRP1/ABCC1) belongs to the ATP-binding cassette transporter superfamily and is capable of conferring resistance to a broad range of chemotherapeutic agents and transporting structurally diverse conjugated organic anions. In this study, we found that substitution of a highly conserved tryptophan at position 1246 with cysteine (W1246C-MRP1) in the putative last transmembrane segment (TM17) of MRP1 eliminated 17β-estradiol 17-(β-d-glucuronide) (E217βG) transport by membrane vesicles prepared from transiently transfected human embryonic kidney cells while leaving the capacity for leukotriene C4- and verapamil-stimulated glutathione transport intact. In addition, in contrast to wild-type MRP1, leukotriene C4transport by the W1246C-MRP1 protein was no longer inhibitable by E217βG, indicating that the mutant protein had lost the ability to bind the glucuronide. A similar phenotype was observed when Trp1246 was replaced with Ala, Phe, and Tyr. Confocal microscopy of cells expressing Trp1246 mutant MRP1 molecules fused at the C terminus with green fluorescent protein showed that they were correctly routed to the plasma membrane. In addition to the loss of E217βG transport, HeLa cells stably transfected with W1246C-MRP1 cDNA were not resistant to theVinca alkaloid vincristine and accumulated levels of [3H]vincristine comparable to those in vector control-transfected cells. Cells expressing W1246C-MRP1 were also not resistant to cationic anthracyclines (doxorubicin, daunorubicin) or the electroneutral epipodophyllotoxin VP-16. In contrast, resistance to sodium arsenite was only partially diminished, and resistance to potassium antimony tartrate remained comparable to that of cells expressing wild-type MRP1. This suggests that the structural determinants required for transport of heavy metal oxyanions differ from those for chemotherapeutic agents. Our results provide the first example of a tryptophan residue being so critically important for substrate specificity in a eukaryotic ATP-binding cassette transporter.
Temperature Gradient Gel Electrophoresis Analysis of 16S rRNA from Human Fecal Samples Reveals Stable and Host-Specific Communities of Active Bacteria

ABSTRACT The diversity of the predominant bacteria in the human gastrointestinal tract was studied by using 16S rRNA-based approaches. PCR amplicons of the V6 to V8 regions of fecal 16S rRNA and ribosomal DNA (rDNA) were analyzed by temperature gradient gel electrophoresis (TGGE). TGGE of fecal 16S rDNA amplicons from 16 individuals showed different profiles, with some bands in common. Fecal samples from two individuals were monitored over time and showed remarkably stable profiles over a period of at least 6 months. TGGE profiles derived from 16S rRNA and rDNA amplicons showed similar banding patterns. However, the intensities of bands with similar mobilities differed in some cases, indicating a different contribution to the total active fraction of the prominent fecal bacteria. Most 16S rRNA amplicons in the TGGE pattern of one subject were identified by cloning and sequence analysis. Forty-five of the 78 clones matched 15 bands, and 33 clones did not match any visible band in the TGGE pattern. Nested PCR of amplified 16S rDNA indicated preferential amplification of a sequence corresponding to 12 of the 33 nonmatching clones with similar mobilities in TGGE. The sequences matching 15 bands in the TGGE pattern showed 91.5 to 98.7% homology to sequences derived from differentClostridium clusters. Most of these were related to strains derived from the human intestine. The results indicate that the combination of cloning and TGGE analysis of 16S rDNA amplicons is a reliable approach to monitoring different microbial communities in feces.
Communication between general practitioners and chiropractors.

OBJECTIVE Good communication between health care professionals has proved to be important in ensuring high standards of care. Patients have shown an increased use of complementary medicine (eg, chiropractic) in addition to conventional medicine. However, this does not automatically guarantee good cooperation and communication between complementary practitioners and conventional practitioners. The objective of this study was to assess the nature and quality of communication between general practitioners and chiropractors (in The Netherlands) and to look for areas for improvement. DESIGN AND SETTING Postal questionnaires were sent to general practitioners requesting personal and practice details and asking about their knowledge of chiropractic, present communications, opinions on chiropractic terminology, and preferences with regard to communications with patients. SUBJECTS A total of 252 general practitioners in 84 Dutch cities. RESULTS A total of 115 questionnaires (46%) were returned. Almost all of the general practitioners had at least heard of chiropractic. Most information came from patients who were treated by chiropractors (78%). Only 10% of the general practitioners refer their patients to a chiropractor on a regular basis. Referral of patients was found to be significantly related to the general practitioners' perceived knowledge of chiropractic and positive opinions regarding their past communications with chiropractors. More than 80% of the general practitioners said that they were interested in receiving (or continuing to receive) feedback reports, even if they did not personally refer the patient to the chiropractor. Chiropractic feedback reports often seem to contain confusing terminology (40%), which might negatively influence communication (66%). General practitioners preferred a typed (88%), short (69%) feedback report, preferably sent after the last treatment (72%). CONCLUSIONS The results of this study show most general practitioners to have a neutral to positive attitude toward communication with chiropractors. The general practitioners' preferences with regard to the technical aspects of a feedback report concur with the results of similar surveys in the field and can be used as guidelines for written communications. Factors that negatively influence communication between general practitioners and chiropractors seem to be confusing terminology, a limited knowledge of chiropractic, and bad experiences in previous communications. Recognition and illumination of these factors is a prerequisite to the development of good communication.
A Zebrafish Model of Myelodysplastic Syndrome Produced through tet2 Genomic Editing

ABSTRACT The ten-eleven translocation 2 gene (TET2) encodes a member of the TET family of DNA methylcytosine oxidases that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to initiate the demethylation of DNA within genomic CpG islands. Somatic loss-of-function mutations of TET2 are frequently observed in human myelodysplastic syndrome (MDS), which is a clonal malignancy characterized by dysplastic changes of developing blood cell progenitors, leading to ineffective hematopoiesis. We used genome-editing technology to disrupt the zebrafish Tet2 catalytic domain. tet2m/m (homozygous for the mutation) zebrafish exhibited normal embryonic and larval hematopoiesis but developed progressive clonal myelodysplasia as they aged, culminating in myelodysplastic syndromes (MDS) at 24 months of age, with dysplasia of myeloid progenitor cells and anemia with abnormal circulating erythrocytes. The resultant tet2m/m mutant zebrafish lines show decreased levels of 5hmC in hematopoietic cells of the kidney marrow but not in other cell types, most likely reflecting the ability of other Tet family members to provide this enzymatic activity in nonhematopoietic tissues but not in hematopoietic cells. tet2m/m zebrafish are viable and fertile, providing an ideal model to dissect altered pathways in hematopoietic cells and, for small-molecule screens in embryos, to identify compounds with specific activity against tet2 mutant cells.
The PAWS score: validation of an early warning scoring system for the initial assessment of children in the emergency department

Objective: To devise a physiology-based scoring system for assessment of children presenting to the emergency department (ED) and to validate the system retrospectively. Study design: Age-dependent physiological parameters designed to reflect the cardiovascular, respiratory and neurological status of patients presenting to the ED were included in a scoring system called the Paediatric Advanced Warning Score (PAWS). A retrospective pilot evaluation was performed to validate PAWS. Setting and patients: PAWS scores were calculated retrospectively for 46 consecutive children who required admission from the ED to the paediatric intensive care unit (PICU) and for 49 control children who were admitted from the ED to the general paediatric ward. Main outcome measures: To validate the PAWS score, we determined if this score was able to identify patients who require admission to the PICU and were therefore significantly unwell. Results: The PAWS score area under the receiver operating characteristic curve was 0.86. Using a trigger score of 3 or above, PAWS was able to identify patients requiring PICU admission with a sensitivity of 70% and a specificity of 90%. Conclusions: This pilot study has shown that a physiology-based scoring system can help to identify children in the ED requiring PICU admission. Future prospective validation of PAWS is necessary to assess its ability to identify all children in need of urgent assessment in the ED.
Massive MIMO two-way relay networks with channel imperfections

This paper investigates the impact of co-channel interference (CCI), imperfect channel state information (CSI) and pilot contamination for multi-pair massive multiple-input multiple-output (MIMO) two-way relay networks (TWRNs). We consider a multi-cell TWRN system consisting of single-antenna user nodes and amplify-and-forward (AF) relay nodes having very large antenna arrays. Under the aforementioned channel imperfections, the asymptotic signal-to-interference-noise ratio and asymptotic sum rate expressions are derived in closed-form whenever the number of relay antennas grows unbounded with respect to the number of user nodes. For perfect CSI case, the transmit power at the user nodes and the relay can be scaled down inversely proportional to the number of antennas at the relay. Moreover, for the imperfect CSI case, these transmit powers can only be scaled down inversely proportional to the square-root of the relay antenna count. Thus, even with imperfect CSI, the benefits of employing a massive MIMO-enabled relay on transmit power savings are significant. Moreover, our analysis shows that although the detrimental effect of CCI can be asymptotically negated completely, the residual interference due to pilot contamination cannot be mitigated even in the limit of infinitely many relay antennas.
Gene Expression Profiling in Perilesional and Contralateral Areas after Ischemia in Rat Brain

Structural and functional reorganization in the vicinity of damaged neocortex and other connected brain areas seems to be responsible for postlesional functional recovery. To better understand the molecular mechanisms underlying this type of plasticity, gene expression patterns were analyzed by using DNA macroarrays comprising 1176 genes. Circumscribed unilateral infarcts consistently affecting the forelimb area of the motor cortex were induced photochemically in adult rats. Ten days after lesioning, cortical gene expression fingerprints were evaluated from an area adjacent to the lesion as well as two contralateral areas of motor and somatosensory cortex. Discrete regions showed distinct expression patterns. Upregulation was observed of different members of transcription factors, immediate early genes, neuronal signaling as well as neuronal growth and structure-associated genes, ipsilaterally (six genes) and/or contralaterally (eight genes in the motor and seven in the somatosensory cortex). In contrast, downregulations were restricted to ipsilateral areas and included genes coding for ion channels, transport proteins, mediators of metabolic pathways, and intracellular transducers (14 genes). A subset of these regulations were further confirmed by real-time polymerase chain reaction (TaqMan assay). At least part of the detected regulations, in particular those of the contralateral hemisphere, are likely to underlie plasticity processes.
Virological Outcome and Management of Persistent Low-Level Viraemia in HIV-1-Infected Patients: 11 Years of the Swiss HIV Cohort Study

Background Management of persistent low-level viraemia (pLLV) in patients on combined antiretroviral therapy (cART) with previously undetectable HIV viral loads (VLs) is challenging. We examined virological outcome and management among patients enrolled in the Swiss HIV Cohort Study (SHCS). Methods In this retrospective study (2000–2011), pLLV was defined as a VL of 21–400 copies/ml on ≥ three consecutive plasma samples with ≥8 weeks between first and last analyses, in patients undetectable for ≥24 weeks on cART. Control patients had ≥ three consecutive undetectable VLs over ≥32 weeks. Virological failure (VF), analysed in the pLLV patient group, was defined as a VL>400 copies/ml. Results Among 9,972 patients, 179 had pLLV and 5,389 were controls. Compared to controls, pLLV patients were more often on unboosted protease inhibitor (PI)-based (adjusted odds ratio [aOR; 95% CI] 3.2 [1.8, 5.9]) and nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-only combinations (aOR 2.1 [1.1, 4.2]) than on non-nucleoside reverse transcriptase inhibitor and boosted PI-based regimens. At 48 weeks, 102/155 pLLV patients (66%) still had pLLV, 19/155 (12%) developed VF and 34/155 (22%) had undetectable VLs. Predictors of VF were previous VF (aOR 35 [3.8, 315]), unboosted PI-based (aOR 12.8 [1.7, 96]) or NRTI-only combinations (aOR 115 [6.8, 1,952]), and VLs>200 during pLLV (aOR 3.7 [1.1, 12]). No VF occurred in patients with persistent very LLV (21-49 copies/ml; n=26). At 48 weeks, 29/39 patients (74%) who changed cART had undetectable VLs, compared with 19/74 (26%) without change (P <0.001). Conclusions Among patients with pLLV, VF was predicted by previous VF, cART regimen and VL≥200. Most patients who changed cART had undetectable VLs 48 weeks later. These findings support cART modification for pLLV>200 copies/ml.