Miracle-dz/UniFAR-FTUs huggingface dataset:
Left Atrial 4-Dimensional Flow Magnetic Resonance Imaging: Stasis and Velocity Mapping in Patients With Atrial Fibrillation

ObjectivesLeft atrial (LA) 4-dimensional flow magnetic resonance imaging (MRI) was used to derive anatomic maps of LA stasis, peak velocity, and time-to-peak (TTP) velocity in patients with atrial fibrillation (AF) and to identify relationships between LA flow with LA volume and patient characteristics. Materials and MethodsFour-dimensional flow MRI for the in vivo assessment of time-resolved 3-dimensional LA blood flow velocities was performed in 111 subjects: 42 patients with a history of AF and in sinus rhythm (AF-sinus), 39 patients with persistent AF (AF-afib), 10 young healthy volunteers (HVs), and 20 age-appropriate controls (CTRL). Data analysis included the 3-dimensional segmentation of the LA and the calculation of LA stasis, peak velocity, and TTP maps. Regional LA flow dynamics were quantified by calculating mean stasis, peak velocity, and TTP in the LA center region and the region adjacent to the LA wall. ResultsA sensitivity analysis identified thresholds for global LA stasis (<0.1 m/s) and peak velocity (top 5% LA velocities), which detected significant differences between AF patients and controls for global LA stasis (HV, 25% ± 5%; CTRL, 29% ± 10%; AF-sinus, 41% ± 13%; AF-afib, 52% ± 17%) and peak velocity (HV, 0.43 ± 0.02 m/s; CTRL, 0.37 ± 0.04 m/s; AF-sinus, 0.33 ± 0.05 m/s; AF-afib, 0.30 ± 0.05 m/s). Regional analysis revealed significantly increased stasis at both LA center and wall for AF patients compared with age-appropriate controls (29%–84% difference, P < 0.006) and for AF-afib versus AF-sinus patients (22%–30% difference, P < 0.004). In addition, stasis close to the LA wall was significantly elevated (P < 0.001) compared with the LA center for all subject groups. Multiple regressions revealed significant (R2Adj = 0.45–0.50, P < 0.001) relationships between impaired global LA flow (reduced velocity and increased stasis) with age (|&bgr;| = 0.27–0.50, P < 0.002) and LA volume (|&bgr;| = 0.26–0.50, P < 0.003). ConclusionsAtrial 4-dimensional flow MRI detected changes in global and regional LA flow dynamics associated with AF, age, and LA volume. Longitudinal studies are needed to test the diagnostic value of LA flow metrics as potential risk factors for thromboembolic events.
Clinical significance of Fusobacterium nucleatum, epithelial–mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients

Colorectal cancer (CRC) is a common digestive malignancy and emerging studies have closely linked its initiation and development with gut microbiota changes. Fusobacterium nucleatum (Fn) has been recently identified as a pathogenic bacteria for CRC; however, its prognostic significance for patients is poorly investigated and is less for patients within late stage. Therefore, in this study, we made efforts to analyze its level and prognostic significance in a retrospective cohort of 280 stage III/IV CRC patients. We found that the Fn level was abnormally high in tumor tissues and correlated with tumor invasion, lymph node metastasis status, and distant metastasis. We also identified it as an independent adverse prognostic factor for cancer-specific survival (CSS) and disease-free survival (DFS). The following subgroup analysis indicated that Fn level could stratify CSS and DFS in stage IIIB/C and IV patients but failed in stage IIIA patients. In addition, stage III/IV patients with low Fn level were found to benefit more from adjuvant chemotherapy than those with high Fn level, in terms of DFS. Finally, we analyzed the expression and clinical significance of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) and cancer stem cell (CSC) markers (Nanog, Oct-4, and Sox-2) in CRC tissues. The results indicated that N-cadherin, Nanog, Oct-4, and Sox-2 were adverse prognostic factors in these patients, while the opposite was true for E-cadherin. More importantly, expression of E-cadherin, N-cadherin, and Nanog was significantly correlated with Fn level in tumor tissues, suggesting the potential involvement of Fn in EMT-CSC cross talk during CRC progression. Taken together, these findings indicate that Fn is a novel predictive biomarker for clinical management in stage III/IV patients, and targeting Fn may be an effective adjuvant approach for preventing CRC metastasis and chemotherapy resistance.
Quality of Life in Animals as a New Outcome for Surgical Research: G-CSF as a Quality of Life Improving Factor

Sepsis is still a major problem in human medicine with a high mortality rate. Nearly all attempts to improve the outcome of septic patients with immune modulators failed. In most of these trials only mechanistic endpoints such as mortality rate, complication rate, cytokine levels and physiological parameters were assessed. Only in a very few trials quality of life had been chosen as primary endpoint. In basic research and especially in animal experiments in the field of sepsis and oncology, only molecular investigations which explain drug and treatment interactions were in the focus of the scientific community. Animal models simulating clinical complexity and investigating outcomes like quality of life were very rare. The aim of this study was to demonstrate alterations in sickness behaviour – the animal equivalent to quality of life in man – in rats as a response to sepsis after prophylaxis with G-CSF and antibiotics. Sickness behaviour was assessed by measurement of core body temperature, food and water intake, locomotor activity and circadian rhythm of these parameters. Complex animal experiments in rats were performed including anaesthesia, antibiotic and cytokine (G-CSF) prophylaxis, volume substitution, laparotomy, contamination and infection with human faecal suspension and postoperative analgesia. In group A (sham) and D (antibiotic + G-CSF) the mortality rate was 0% , but in group B (no prophylaxis) 33% (3/9) and in group C (antibiotic prophylaxis) 11% (1/9) of the animals died. Before infection all rats showed clear circadian patterns of locomotor activity and body temperature with physiologically higher values during the night-time. Immediately after operation and infection temperature increased, water and food intake, locomotor activity decreased and circadian rhythms were lost. Body temperature and water consumption were already normalised at day 2 after infection in all groups. Normal food intake was re-established in group C and D at day 3 while one more day was needed for recovery in Group C. Restoration of locomotor activity occurred in group D at day 5, in group C at day 7. In group B locomotor activity remained suppressed during the whole observation period of 8 days postoperatively. In conclusion, in septic rats sickness behaviour, an equivalent to quality of life in humans, is improved rapidly by a prophylaxis with G-CSF in combination with antibiotics and can be used as a new outcome in preclinical surgical research.
Target detection and parameter estimation for MIMO radar systems

We investigate several target detection and parameter estimation techniques for a multiple-input multiple-output (MIMO) radar system. By transmitting independent waveforms via different antennas, the echoes due to targets at different locations are linearly independent of each other, which allows the direct application of many data-dependent beamforming techniques to achieve high resolution and excellent interference rejection capability. In the absence of array steering vector errors, we discuss the application of several existing data-dependent beamforming algorithms including Capon, APES (amplitude and phase estimation) and CAPES (combined Capon and APES), and then propose an alternative estimation procedure, referred to as the combined Capon and approximate maximum likelihood (CAML) method. Via several numerical examples, we show that the proposed CAML method can provide excellent estimation accuracy of both target locations and target amplitudes. In the presence of array steering vector errors, we apply the robust Capon beamformer (RCB) and doubly constrained robust Capon beamformer (DCRCB) approaches to the MIMO radar system to achieve accurate parameter estimation and superior interference and jamming suppression performance.
Identification of a Novel Lipid Raft-Targeting Motif in Src Homology 2-Containing Phosphatase 11

The tyrosine phosphatase Src homology 2-containing phosphatase 1 (SHP-1) is a key negative regulator of TCR-mediated signaling. Previous studies have shown that in T cells a fraction of SHP-1 constitutively localizes to membrane microdomains, commonly referred to as lipid rafts. Although this localization of SHP-1 is required for its functional regulation of T cell activation events, how SHP-1 is targeted to the lipid rafts was unclear. In this study, we identify a novel, six-amino acid, lipid raft-targeting motif within the C terminus of SHP-1 based on several biochemical and functional observations. First, mutations of this motif in the context of full-length SHP-1 result in the loss of lipid raft localization of SHP-1. Second, this motif alone restores raft localization when fused to a mutant of SHP-1 (SHP-1 ΔC) that fails to localize to rafts. Third, a peptide encompassing the 6-mer motif directly binds to phospholipids whereas a mutation of this motif abolishes lipid binding. Fourth, whereas full-length SHP-1 potently inhibits TCR-induced tyrosine phosphorylation of specific proteins, expression of a SHP-1-carrying mutation within the 6-mer motif does not. Additionally, although SHP-1 ΔC was functionally inactive, the addition of the 6-mer motif restored its functionality in inhibiting TCR-induced tyrosine phosphorylation. Finally, this 6-mer mediated targeting of SHP-1 lipid rafts was essential for the function of this phosphatase in regulating IL-2 production downstream of TCR. Taken together, these data define a novel 6-mer motif within SHP-1 that is necessary and sufficient for lipid raft localization and for the function of SHP-1 as a negative regulator of TCR signaling.
Interfering with Apoptosis: Ca2+-Binding Protein ALG-2 and Alzheimer's Disease Gene ALG-3

Two apoptosis-linked genes, named ALG-2 and ALG-3, were identified by means of a functional selection strategy. ALG-2 codes for a Ca2+-binding protein required for T cell receptor-, Fas-, and glucocorticoid-induced cell death. ALG-3, a partial complementary DNA that is homologous to the familial Alzheimer's disease gene STM2, rescues a T cell hybridoma from T cell receptor- and Fas-induced apoptosis. These findings suggest that ALG-2 may mediate Ca2+-regulated signals along the death pathway and that cell death may play a role in Alzheimer's disease.
The Internal Bony Architecture of the Sacrum

Study Design. Radiographic and direct quantitative measurements were made of the cortical and the trabecular anatomy of the sacrum. Objectives. To define the trabecular patterns and the cortical thickness of the sacrum. Summary of Background Data. The sacrum is a frequent site of internal fixation. In previous anatomic studies, investigators have focused on specific dimensional measurements of the sacrum, whereas others have described the anatomic course of the anterior sacral neurovascular or visceral structures. Computed tomographic imaging also has been used to quantify the sacral trabecular bone density. The internal architecture of the sacrum has yet to be described in detail. Methods. Seventeen cadaveric sacra were studied by computed tomographic imaging and then were sectioned at 3‐mm intervals in the axial or sagittal plane. The cortical thickness of each section was measured under microscopic visualization. The sections were radiographed with high‐resolution imaging to delineate their trabecular patterns. Results. The trabecular bone was densest adjacent to the endplates. The sacral body trabeculae were arranged in a cruciate pattern, and bony atrophy occurred in a systematic fashion. An alar void was a consistent finding in all specimens with definable boundaries. The cortical thickness was uniform throughout the surface of each specimen. The computed tomographic images correlated with the anatomy observed in the cadaveric sections. Conclusion. The internal bony architecture of the sacrum has several consistent features. The relatively uniform cortical thickness seen in each sacral specimen may have clinical significance in the internal fixation of this region.
Urine‐based testing for Chlamydia trachomatis using polymerase chain reaction, leucocyte esterase and urethral and cervical smears

The performance of Roche polymerase chain reaction (PCR) Amplicor to detect Chlamydia trachomatis in first‐voided urine specimens from 422 males and 456 females attending two clinics for sexually transmitted infections was evaluated in comparison with cultures of urethral and cervical specimens. At the same time, the ability of leucocyte esterase (LE) in first‐voided urine and the presence of leucocytes in urethral and cervical smears to identify C. trachomatis‐infected individuals based on PCR and culture was determined. The prevalence of C. trachomatis infection was 10.9 % in men and 7.7 % in women. Sensitivity, specificity, positive predictive value and negative predictive value of Amplicor was 93.5 %, 99.7 %, 97.7 % and 99.2 % in males and 91.4 %, 99.5 %, 94.1 % and 99.3 % in females. All Chlamydia‐infected men were identified by means of a combination of urethritis (⩾4 leucocytes in the urethral smear) and/or a positive LE test in urine, although the specificity was only 42.2 %. In women, the combination of urethritis and/or cervicitis and/or a positive LE test identified 85.7 % of Chlamydia‐infected patients with a specificity of 38.2 %. It is concluded that a combination of urethral and/or cervical smears and LE testing of urine can be used as a screening test to select patients, especially males, for specific C. trachomatis testing.
Circulating non-hematological cells during cardiopulmonary bypass: new findings in cardiac surgery procedures

Background: Several factors have been historically advocated to explain the coagulative and inflammatory disorders following cardiopulmonary bypass (CPB). In this paper, we describe the presence of circulating non-hematological cells, introduced within the bloodstream during CPB. We defined the origin of the cells and tested their impact on coagulation. Methods: We collected peripheral arterial blood samples in twenty consecutive coronary artery bypass graft cases at four different surgical moments and assessed the presence and nature of circulating cells with the use of the CELLSEARCH® Test, immunocytochemistry and immunofluorescence, evaluating the expression of cytokeratin and calretinin. The effect of the circulating non-hematological cells on coagulation was tested in vitro, using the ROTEM assay. Results: A mean of 263.85 ± 57.5 (median 258.5) cells were present in the samples following the suction of blood from the surgical field while all the other samples were negative (zero cells) (p<0.00001). Immunologic tests confirmed the mesothelial origin of the cells. The ROTEM® assay of the blood samples contaminated by the mesothelial cells presented longer clotting times (53.4 ± 8.2 secs 48.3 ± 8.9 sec, p=0.05), longer clot formation times (137.1 ± 31.5 sec vs 111.9 ± 25.2 sec, p=0.009), smaller alfa angle amplitudes (66.7 ± 9.1° vs 71.1 ± 5.1°, p=0.04) and maximum clot firmness times (59.0 ± 5.4 sec vs 61.9 ±4.6 sec, p=0.004) than the controls. Conclusion: The presence of circulating non-hematological cells during CPB with a mesothelial immunophenotype alters in vitro coagulation assays. This finding can help to further understand the pathophysiology of CPB.
State of the art: radiolabeled microspheres treatment for liver malignancies

Importance of the field: Metastatic tumours of the liver are responsible for significant morbidity and mortality, and only a small percentage is resectable with curative intent. Hepatic artery radioembolization (RE) with yttrium-90 (90Y)-loaded microspheres is an alternative treatment for patients with unresectable primary or secondary liver tumours, especially in cases of metastatic colorectal cancer (mCRC) and hepatocellular carcinoma (HCC). Areas covered in this review: Data from recent relevant clinical trials with 90Y-RE are discussed, focusing on response rate assessments and treatment outcome. What the reader will gain: Current data show that 90Y-RE combined with radiosensitizing chemotherapy is a safe and efficient modality that extends the time to progression in liver mCRC and unresectable HCC, although no survival benefits have been demonstrated. The treatment response after 90Y-RE seems to be better assessed using metabolic response assessments with serial fluorodeoxyglucose positron emission tomography (FDG-PET) in cases of FDG-avid tumours than with morphological criteria measured on computed tomography or magnetic resonance imaging (RECIST or WHO trials). Predictive models using multimodality imaging approaches (PET-SPECT-CT image fusion algorithms) have been proposed to better select patients for 90Y-RE. The optimal routine role of radioembolization remains to be defined; the complexity and wide availability of available therapeutic alternatives confuses the role of a locoregional treatment in a generalized disease. Take home message: 90Y-RE is a safe and efficient treatment modality in salvage therapy of colorectal cancer metastatic to the liver and in unresectable HCC. However, it has still to find its place as a first- or second-line treatment of mCRC in combination with or as an alternative to available biological agents. The role of 90Y-RE in other solid tumour types metastatic to the liver is much more uncertain and investigations in clinical situations in which disease is strictly limited to the liver are required. Pretherapeutic work-up, initially developed to explore hepatic vasculature and to assess lung shunting, might be able to predict treatment outcome, allowing a better patient selection.
Identification of 13 novel NLRP7 mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region

Background: NLRP7 (NALP7) has recently been identified as the causative gene for familial recurrent hydatidiform mole (FRHM), a rare autosomal recessive condition in which affected women have recurrent molar pregnancies of diploid biparental origin. To date only a small number of affected families have been described. Our objectives were to investigate the diversity of mutations and their localisation to one or both isoforms of NLRP7, by screening a large series of women with FRHM and to examine the normal expression of NLRP7 in ovarian tissue. Methods: Fluorescent microsatellite genotyping of molar tissue was used to establish a diagnosis of FRHM. Twenty families were subsequently screened for mutations in NLRP7 using DNA sequencing. Expression of NLRP7 in the ovary was examined by immunohistochemical staining. Results: 16 different mutations were identified in the study, 13 of which were novel. Missense mutations were found to be present in transcript variant 2 of NLRP7 and cluster in the leucine-rich region (LRR). A man with two affected sisters and homozygous for the p.R693P mutation had normal reproductive outcomes. In the normal human ovary, NLRP7 expression is confined to the oocytes and present at all stages from primordial to tertiary follicles. Conclusion: 13 novel mutations in NLRP7 were identified. We confirm that mutations in NLRP7 affect female but not male reproduction, and provide evidence that transcript variant 2 of NLRP7 is the important isoform in this condition. The mutation clustering seen confirms that the LRR is critical for normal functioning of NLRP7.
A risk model for congenital syphilis in infants born to mothers with syphilis treated in gestation: a prospective cohort study

Objective To explore the risk factors underlying congenital syphilis (CS) and to build a hazards model to assess the risk of CS in offspring born to mothers with syphilis treated in gestation. Methods This prospective study observed 554 pregnant women with syphilis and their offspring recruited from August 2002 to May 2007 in Shenzhen Centre for Chronic Disease Control and Prevention. After treatment, all the women were followed up until the diagnosis of CS in their offspring was confirmed or denied. Comparisons were made between women bearing infants with CS and women bearing infants without CS to reveal the risk factors for CS. ORs and their 95% CI were calculated for each risk factor by using logistical regression analysis. Results Twenty-nine (5.2%) infants were diagnosed with CS. Univariable analyses showed that the reciprocal logarithm of the titre of non-treponemal antibodies in mothers (log (1/T); OR=11.18, p<0.001), gestational week (GW) at treatment (OR=1.10, p<0.001) and the interaction between these two variates (OR=1.09, p<0.001) was associated with CS. Multivariable analysis showed that only the interaction was significantly associated with CS (OR=1.09, p=0.047). Conclusions The risk of CS could be predicted by the interaction between GW×log (1/T). Early treatment given to women with syphilis during antenatal care may be the only effective method to decrease the risk of CS.
Effect of prenatal steroids on potassium balance in extremely low birth weight neonates.

OBJECTIVE Potassium is the most abundant intracellular cation and plays an important role in a variety of cell functions. Potassium homeostasis and regulation are important aspects of fluid and electrolyte homeostasis in extremely low birth weight (ELBW) infants. Because prenatal steroid (PNS) treatment promotes maturation of many epithelial cell systems, we sought to determine whether PNS affects potassium homeostasis in ELBW infants (<1000 g) during the first week of life. METHOD Serum potassium (SK) concentration, potassium intake and output, and renal clearance were collected prospectively each day during the first week of life. Infants whose mothers received a full course of steroids before delivery (PNS group: n = 16) were compared with those infants whose mothers did not receive steroids (nonsteroid group [NSG]: n = 14). The decision to treat with PNS was made entirely by the obstetric staff in a nonrandomized manner. Potassium intake and excretion and serum and urine electrolytes were measured every 12 hours, and urine output was monitored every 2 to 3 hours. Hyperkalemia was defined as SK >6. 5 mmol/L in a nonhemolyzed sample on at least 1 measurement from a central line. RESULTS There were no significant differences between the groups in gestational age, Apgar score, and birth weight. SK increased initially after birth in the absence of exogenous K intake in all infants, then subsequently decreased and stabilized by day 4 of life. The peak SK was significantly lower in the PNS group than in the NSG group (5.2 +/-.2 mmol/L vs 6.2 +/-.4 mmol/L). Moreover, the peak SK was higher than 6.5 mmol/L in 70% of the NSG infants and in none of the PNS group. Hyperkalemia occurred in the NSG infants within the first 2 days when urine output was significantly lower than in PNS infants. SK peaked in the absence of potassium intake with similar potassium excretion in both groups. PNS infants had similar cumulative potassium intake with a lower cumulative potassium excretion than did NSG infants. PNS infants had a significantly less negative potassium balance than did NSG infants by day 7 of life (-1.0 mmol/kg vs -7.0 mmol/kg). There was no statistical difference in the daily serum creatinine levels, fractional excretion of potassium, and in the daily creatinine clearance between the 2 groups. CONCLUSION We conclude that treatment with PNS prevents the nonoliguric hyperkalemia known to occur in ELBW neonates. We speculate that PNS induces upregulation of cell membrane sodium, potassium-adenosinetriphosphatase activity in the fetus. The differences in negative potassium balance may be accounted for by stabilization of cell membranes that may result in a decrease in potassium shift from intracellular to extracellular compartments.