Miracle-dz/UniFAR-FTUs huggingface dataset:
Dominant effector memory characteristics, capacity for dynamic adaptive expansion, and sex bias in the innate Vα24 NKT cell compartment

Vα24 natural killer T (NKT) cells are innate immune cells that recognize self and nonself glycolipids presented by CD1d molecules, and play immunoregulatory roles in autoimmunity and tumorimmunity. We have investigated the circulating Vα24 NKT cells in a large cohort of human subjects. CCR7– CD45RO+ effector memory cells dominated both CD4+ and CD4 NKT subsets, while a minority displayed a central memory phenotype. CD4– central memory NKT cells, however, were atypical in that they largely lacked CD62L expression. Overall, CD4– NKT cells displayed a functional phenotype with effector characteristics, while the CD4+ subset appeared immunoregulatory. Interestingly, NKT cell numbers in blood varied widely between subjects, and elevated numbers of these cells were much more common in women than in men. The CD4+ subset dominated the NKT cell compartment in both sexes, while circulating NKT cell numbers above 0.1% were associated with an expanded CD4– subset. Although NKT cell numbers were generally stable over time, we describe a dynamic fivefold expansion that was associated with a skewing of the NKT CD4+:CD4– ratio that persisted after numbers returned to base line. Thus, the two NKT cell subsets display different properties and dynamics that will influence theirfunction as innate immunoregulatory and effector cells.
Imaging Plasticity in Cochlear Implant Patients

Auditory re-afferentation by cochlear implants (CI) offers a unique opportunity to study directly from within the auditory modality plastic changes taking place at organisational levels up to the supra- or polymodal level. These plastic changes resulting from deafness and chronic electrical stimulation can be studied using modern neuroimaging techniques. In this paper, we review the available techniques and the experimental approaches to human studies of plasticity, we discuss the different forms of plasticity that are associated with cochlear implantation and we point to the interest of imaging studies for providing a prognosis of functional outcome after implantation.
Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly

ABSTRACT In contrast to enveloped viruses, the mechanisms involved in membrane penetration by nonenveloped viruses are not as well understood. In these studies, we determined the relationship between adenovirus (Ad) capsid disassembly and the development of membrane lytic activity. Exposure to low pH or heating induced conformational changes in wild-type Ad but not in temperature-sensitive Ad (ts1) particles that fail to escape the early endosome. Wild-type Ad but not ts1 particles permeabilized model membranes (liposomes) and facilitated the cytosolic delivery of a ribotoxin. Alterations in wild-type Ad capsids were associated with the exposure of a pH-independent membrane lytic factor. Unexpectedly, this factor was identified as protein VI, a 22-kDa cement protein located beneath the peripentonal hexons in the viral capsid. Recombinant protein VI and preprotein VI, but not a deletion mutant lacking an N-terminal amphipathic α-helix, possessed membrane lytic activity similar to partially disassembled virions. A new model of Ad entry is proposed based on our present observations of capsid disassembly and membrane penetration.
Temperature and oxygen effects on C-photosynthate unloading and accumulation in developing soybean seeds.

The environmental sensitivity of the processes associated with the import of photosynthate by developing soybean seeds was investigated within intact fruit and with excised, immature embryos. Intact pods of field-grown (Glycine max [L.] Merr.) Amsoy 71 soybeans were subjected to localized regimes of 0, 21, or 100% O(2) and 15, 25, or 35 degrees C during pulsechase translocation experiments and, 2.5 hours later, the uptake and distribution of (14)C-photosynthate among dissected fruit tissues determined. In other experiments, excised embryos were incubated in [(14)C]sucrose solutions under various experimental conditions to separate the effects of these treatments on accumulation by the embryos from those which may operate on phloem unloading in the maternal seedcoat.Import of (14)C-photosynthate by intact soybean fruit was both temperature- and O(2)-dependent. This dependency was shown to occur only within the seeds; import by the pod walls was essentially insensitive to fruit temperature or O(2) treatments. The embryos of anaerobic fruit were completely unlabeled, regardless of fruit temperature. But under anaerobic in vitro incubation conditions, uptake of [(14)C]sucrose in excised embryos was only 30% less than that in aerobic in vitro conditions. The data suggest that, within intact fruit, anoxia prevented sucrose efflux from the seed coat phloem and any subsequent uptake by the embryo. The demonstrated energy dependence of phloem unloading may reflect requirements for membrane integrity or energy metabolism in the companion cell-sieve element complex, consistent with a facilitated unloading process.Collectively, these data characterize the environmental sensitivity of photosynthate import in developing soybean fruit. They imply that environmental regulation of import may occur at both the embryo level and at the phloem terminals within the seed coat.
Streptococcus pneumoniae antibody titres in patients with primary antibody deficiency receiving intravenous immunoglobulin (IVIG) compared to subcutaneous immunoglobulin (SCIG)

Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) are effective in the treatment of patients with primary antibody deficiency disorders (PAD). The purpose of this study was to evaluate Streptococcus pneumoniae (Spn) antibody titres to 14 serotypes in patients receiving IVIG compared to SCIG and to correlate Spn antibody levels to clinical outcome. The doses of immunoglobulin (Ig)G/kg/month were similar in both IVIG and SCIG groups. In 11 patients treated with IVIG, Spn antibody titres were ≥ 1·3 μg/ml to 99·4 ± 2·1% of the 14 serotypes at peak IVIG but decreased to 66·9 ± 19·8% at trough IVIG. Loss of Spn titres ≥ 1·3 μg/ml was most frequent for Spn serotypes 1, 4, 9V and 23. This correlated with lower Spn antibody titres to these serotypes at peak IVIG compared to the other serotypes. In 13 patients treated with SCIG, Spn antibody titres were protective to 58·2 ± 23·3% of the serotypes 3–5 days after infusion, similar to trough IVIG. Similarly, the Spn serotypes with the least protective percentages were the same as the ones observed in trough IVIG. There were no annualized serious bacterial infections (aSBI) in either group. However, there were significantly decreased annualized other infections (aOI) in the SCIG group compared to the IVIG‐treated group, 0·8 ± 0·7 versus 2·2 ± 1·2 infections/patient/year (P = 0·004). Breakthrough aOI did not correlate with protective or higher serum Spn antibody titres.
Concept of arteriovenous malformation compartments and surgical management

Abstract Cerebral AVMs are known to be a source of intracranial hemorrhages and epileptic seizures. Their natural history indicates approximately 15% mortality and 35% morbidity over a 15-year period. This significant mortality and morbidity mandates a need for satisfactory treatment of this entity, ideally by elimination of AVMs. Microsurgical resection, endovascular embolization and radiosurgery (irradiation) are the three effective modes of treatment currently available. However, no objective criteria have been established for which mode(s) of treatment should be selected for individual patients with AVMs. Considering the complexity of AVMs and variable conditions of individual patients, neurosurgeons, intravascular interventionalists and radiosurgeons must make their own decisions on how to treat each patient based on their experience. In practice, treatment of small AVMs in non-functional areas is favored equally by each of these specialists, while they tend to avoid treatment of large AVMs, particularly those in functional areas of the brain. The authors report the surgical intervention of large AVMs, including those located in functional areas of the hemisphere by special techniques. One can demonstrate AVM compartments by using angiography and with the aid of color Doppler ultrasonography, each compartment can be outlined and dissected individually until all the compartments are isolated without causing any damage to the surrounding brain and the entireAVM is rendered shrunken and then removed. The concept of compartmental treatment of AVMs may be applied in the future to radiosurgery and intravascular embolization of large AVMs.
Recurrence Plots: a New Tool for Quantification of Cardiac Autonomic Nervous System Recovery after Transplant

Objective To evaluate a possible evolutionary post-heart transplant return of autonomic function using quantitative and qualitative information from recurrence plots. Methods Using electrocardiography, 102 RR tachograms of 45 patients (64.4% male) who underwent heart transplantation and that were available in the database were analyzed at different follow-up periods. The RR tachograms were collected from patients in the supine position for about 20 minutes. A time series with 1000 RR intervals was analyzed, a recurrence plot was created, and the following quantitative variables were evaluated: percentage of determinism, percentage of recurrence, average diagonal length, Shannon entropy, and sample entropy, as well as the visual qualitative aspect. Results Quantitative and qualitative signs of heart rate variability recovery were observed after transplantation. Conclusion There is evidence that autonomic innervation of the heart begins to happen gradually after transplantation. Quantitative and qualitative analyses of recurrence can be useful tools for monitoring cardiac transplant patients and detecting the gradual return of heart rate variability.
Hemodynamic Profile of Patients With Heart Failure and Preserved Ejection Fraction Vary by Age

Background Patients with heart failure with preserved ejection fraction (HFpEF) exhibit a range of cardiovascular phenotypic profiles modified by several common comorbidities. In particular, patients with HFpEF tend to be older; however, it is unclear whether the effects of cardiovascular aging per se modify the expression of HFpEF. We therefore sought to investigate the interaction between age and physiologic profile in patients with HFpEF. Methods and Results We assessed the hemodynamic and metabolic profile of 40 patients with HFpEF. Patients underwent right heart catheterization at rest and during supine cycle ergometry, and were segregated into 2 groups by the median age of the cohort. Older patients with HFpEF demonstrated reduced resting cardiac output (4.8±1.2 L/min versus 5.7±1.1 L/min). With exercise, older patients demonstrated a marked rise in arteriovenous oxygen content difference (10.8±1.8 versus 7.9±2.4 mL, P≤0.001), driven by enhanced oxygen extraction. There was no significant difference in peak pulmonary capillary wedge pressure (30±7 mm Hg versus 27±6, P=0.135), including when indexed to workload (pulmonary capillary wedge pressure/W, 0.88 mm Hg/W versus 0.92; P=0.83). Conclusions Older patients with HFpEF display a different physiological phenotype compared with younger patients, with enhanced oxygen extraction and lower increment in cardiac output to increase oxygen consumption from rest to peak supine exercise. This finding highlights the importance in considering age when considering therapeutic options in patients with HFpEF.
Role of mitogen‐activated protein kinases in the differential regulation of interleukin‐2 by cannabinol

Cannabinoids can paradoxically regulate interleukin‐2 (IL‐2) expressioneither positively or negatively. This study investigated the mechanismresponsible for cannabinol‐mediated IL‐2 modulation. In primary murinesplenocytes and EL4.IL‐2 T cells, the contrasting effects of cannabinolon IL‐2 secretion depended on the magnitude but not the mode of T‐cellactivation. Suboptimal activation of T cells in the presence ofcannabinol produced an enhancement of IL‐2 secretion, which wasparalleled by an increase in nuclear phospho‐extracellular‐regulatedkinase (ERK) 1/2. In contrast, T cells activated with stimulithat were optimized to induce maximal IL‐2 secretion elicited a markedsuppression in the production of this cytokine when cultured in thepresence of cannabinol. Moreover, cannabinol‐mediated enhancement of IL‐2 secretion by splenocytes was attenuated to various degrees bystaurosporine, Ro‐31‐8220, and KN93. These results suggest that theenhancement of IL‐2 secretion by cannabinol is associated with anincrease in ERK mitogen‐activated protein kinase, which is proteinkinase C and calmodulin‐kinase dependent.
Nitric oxide successfully used to treat acute chest syndrome of sickle cell disease in a young adolescent.

OBJECTIVES To report a case of acute chest syndrome (ACS) of sickle cell disease treated successfully with nitric oxide and to review the physiologic effects of nitric oxide and its potential ability to improve outcome in ACS. DESIGN Descriptive case report. SETTING Eighteen-bed pediatric intensive care unit in a university children's hospital. PATIENT A 15-yr-old black male with sickle cell disease, bilateral pulmonary infiltrates, refractory hypoxemia, and unstable hemodynamics. INTERVENTION In addition to exchange transfusion, invasive hemodynamic monitoring, and aggressive ventilatory support, inhaled nitric oxide was administered in the gas mixture in a concentration of 20 ppm for 72 hrs. MEASUREMENTS AND MAIN RESULTS Cardiac output, pulmonary arterial pressure, pulmonary artery occlusion pressure, systemic vascular resistance, pulmonary vascular resistance, shunt fraction, and alveolar-arterial oxygen gradient were compared with and without inhaled nitric oxide. Marked reductions in pulmonary arterial pressure and pulmonary vascular resistance were noted. Cardiac output improved, and shunt fraction and alveolar-arterial oxygen gradient were markedly reduced. The patient required decreased ventilator and hemodynamic support and rapidly made a complete recovery. CONCLUSIONS Nitric oxide may be beneficial for patients with ACS because of its ability to ameliorate pulmonary hypertension and ventilation/perfusion mismatch. Nitric oxide may confer some protection against polymerization of sickle hemoglobin and exert a reversible antiplatelet effect that may be beneficial in ACS. Further study is necessary to determine the safety and efficacy of inhaled nitric oxide as a treatment for ACS.
Lignin Degradation and Humus Formation in Alluvial Soils and Sediments

The contribution of lignin to the formation of humic compounds was examined in different environments of the terrestrial-aquatic interface in the Garonne River valley in southwestern France. Alluvial soils and submerged or nonsubmerged river and pond sediments containing alder, poplar, or willow [14C-lignin]ligno-celluloses were incubated. After a 49-day incubation period, 10 to 15% of labeled lignins in alluvial soils was recovered as evolved 14CO2. In nonsubmerged sediments, 10% of the applied activity was released as 14CO2, and in submerged sediments, only 5% was released after 60 days of incubation. In the different alluvial soils and sediments, the bulk of residual activity (70 to 85%) remained in the two coarsest-grain fractions (2,000 to 100 and 100 to 50 μm). Only 2 to 6% of the residual activity of these two coarse fractions was recovered as humic and fulvic acids, except in the case of alder [14C-lignin]lignocellulose, which had decomposed in a soil collected beneath alders. In this one 55% of the residual activity was extracted as humic substances from the 2,000- to 100-μm fraction. Humic and fulvic acids represented from 6 to 50% of the residual activity in the finest-grain fractions (50 to 20 and 20 to 0 μm). The highest percentages were obtained in soil collected beneath alders and in submerged pond sediment. The contribution of different groups of microorganisms, as well as nutrients and clay content, may influence humic-substance formation in such environments. Physical stability also may be an important factor for complex microbial activity involved in this process.
Cervical spine injury outcome--a review of 101 cases treated in a tertiary referral unit.

UNLABELLED Cervical spinal cord injury (SCI) is a devastating event for the patient and family. It has a huge impact on society because of the intensive resources required to manage the patient in both the acute and rehabilitation phases. Given the resource-limited setting in South Africa, questions are often raised regarding whether the outcome of this group of patients justifies the expense of their care. However local data have not been available to date. OBJECTIVE To evaluate the mortality, morbidity and functional outcome of cervical SCI patients in the South African environment. MATERIAL AND METHODS All cervical SCI patients managed in the acute spinal cord injury unit at Groote Schuur Hospital over a 12-month period were included. Epidemiological data, management, complications, neurological status and change were assessed. Those referred for rehabilitation were followed up in terms of mortality and ambulation status. RESULTS There were 101 patients, with an average age of 34.7 years. Motor vehicle accidents were the commonest cause of injury, with violence contributing 21%. Fifty-nine patients required referral to a rehabilitation unit. Of these, 18 were functional walkers, and only 6 were care-dependent. By 1 year post injury all but 1 patient had been discharged from the health service. Fourteen patients died; in half of these cases injury was at C5 level and above. CONCLUSION Despite cervical SCI being a devastating event, aggressive early intervention yields a better-than-expected 1-year survival rate. Associated problems, such as pressure sores, remain a major problem both for the patient and in terms of health care costs. It is difficult to predict prognosis on presentation because of spinal shock. It is recommended that all patients initially be treated aggressively, with exit strategies in place once all the information is available and a confident assessment of poor prognosis can be made.
The Effect of a Peripheral Block on Inflammation-Induced Prostaglandin E2 and Cyclooxygenase Expression in Rats

BACKGROUND:Peripheral inflammatory pain is associated with an upregulation of spinal cord COX-2 (cyclooxygenase-2), with a subsequent increase in central prostaglandin E2 (PGE2) levels associated with the development of hyperalgesia. In this study, we evaluated the effect of bupivacaine administered via a nerve block or via a systemic route on the spinal expression of PGE2 and COX in a model of peripheral inflammation in rats. METHODS:All rats randomly received three injections: 1) a left subcutaneous hindpaw injection (0.2 mL with either carrageenan 2% w/v or saline), 2) a left sciatic block (0.2 mL with either bupivacaine 0.5% or saline), and 3) a systemic injection (subcutaneous interscapular with 0.2 mL with either bupivacaine 0.5% or saline). Local edema, thermal, and mechanical hyperalgesia as well as cerebrospinal fluid PGE2 concentration and COX-1 and COX-2 expression in the spinal cord in dorsal root ganglions were measured. RESULTS:We confirmed that a bupivacaine block attenuates hyperalgesia and local inflammation in a model of inflammatory pain. This effect was associated with an inhibition of the increase in COX-2 expression induced by peripheral inflammation in dorsal root ganglions and cord. The subsequent production of PGE2 in cerebrospinal fluid was also impaired. Systemic bupivacaine did not modify either the hyperalgesia and local inflammation or COX expression. CONCLUSION:These results constitute a key element strongly suggesting that local anesthetics act at a different level when administered systematically or via a nerve block.
Total Cardiac Denervation in Diabetic Autonomic Neuropathy

Total loss of the autonomic regulation of heart rate is described in a 28-year-old diabetic with extensive autonomic neuropathy. The patient had an almost fixed heart rate that barely responded to any of the tests that stimulate or inhibit the autonomic nerves. Its behavior was similar to that of the transplanted heart.
Phosphoinositide-3-Kinase Catalytic Alpha and KRAS Mutations are Important Predictors of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Advanced Non-small Cell Lung Cancer

Background: Specific mutations of the epidermal growth factor receptor (EGFR) gene are predictive for favorable response to tyrosine kinase inhibitors (TKIs) and are associated with a good prognosis. In contrast, Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation has been shown to predict poor response to such therapy. Nevertheless, tumor that initially responds to EGFR-TKIs almost inevitably becomes resistant later. Other mechanisms of resistance to EGFR inhibitors could involve activating mutations of the other main EGFR effector pathway, i.e., the phosphoinositide-3-kinase/phosphate and tensin homologue deleted from chromosome 10 (PTEN)/alpha serine/threonine protein kinase (AKT) pathway. The aim of this study was to investigate the role of phosphoinositide-3-kinase catalytic alpha (PIK3CA), EGFR, and KRAS gene mutations in predicting response and survival in patients with non-small cell lung cancer (NSCLC) treated with EGFR-TKIs. Patients and Methods: A total of 166 patients with advanced NSCLC treated with EGFR-TKI with available archival tissue specimens were included. PIK3CA, EGFR, and KRAS mutations were analyzed using polymerase chain reaction-based sequencing. Results: EGFR mutation was detected in 25.3% of patients, PIK3CA mutation in 4.1%, and KRAS mutation in 6.7%. PIK3CA mutation correlated with shorter median time to progression (TTP) (p = 0.01) and worse overall survival (OS) (p < 0.001). EGFR mutation (p < 0.0001) correlated with favorable response to TKIs treatment and longer TTP (p < 0.0001). KRAS mutation correlated with progressive disease (p = 0.05) and shorter median TTP (p = 0.003) but not with OS. Cox multivariate analysis including histology and performance status showed that PIK3CA mutation was an independent factor to predict worse OS (p = 0.0001) and shorter TTP (p = 0.03), while KRAS mutation to predict shorter TTP (p = 0.01). Conclusion: PIK3CA and KRAS mutations seem to be indicators of resistance and poor survival in patients with NSCLC treated with EGFR-TKIs.