Miracle-dz/UniFAR-FTUs huggingface dataset:
Digital epidemiology reveals global childhood disease seasonality and the effects of immunization

Significance Disease surveillance systems largely focus on infectious diseases with high mortality, whereas less severe diseases often go unreported. Using chicken pox as an example, we demonstrate that Internet queries can be used as a proxy for disease incidence when reporting is lacking. We established that Google Trends accurately reflected clinical cases in countries with surveillance, and thus population-level dynamics of chicken pox. Then, we discovered robust seasonal variation in query behavior, with a striking latitudinal gradient on a global scale. Next, we showed that real-time data-mining of queries could forecast the timing and magnitude of outbreaks. Finally, our analyses revealed that countries with government-mandated vaccination programs have significantly reduced seasonality of queries, indicating vaccination efforts mitigated chicken pox outbreaks. Public health surveillance systems are important for tracking disease dynamics. In recent years, social and real-time digital data sources have provided new means of studying disease transmission. Such affordable and accessible data have the potential to offer new insights into disease epidemiology at national and international scales. We used the extensive information repository Google Trends to examine the digital epidemiology of a common childhood disease, chicken pox, caused by varicella zoster virus (VZV), over an 11-y period. We (i) report robust seasonal information-seeking behavior for chicken pox using Google data from 36 countries, (ii) validate Google data using clinical chicken pox cases, (iii) demonstrate that Google data can be used to identify recurrent seasonal outbreaks and forecast their magnitude and seasonal timing, and (iv) reveal that VZV immunization significantly dampened seasonal cycles in information-seeking behavior. Our findings provide strong evidence that VZV transmission is seasonal and that seasonal peaks show remarkable latitudinal variation. We attribute the dampened seasonal cycles in chicken pox information-seeking behavior to VZV vaccine-induced reduction of seasonal transmission. These data and the methodological approaches provide a way to track the global burden of childhood disease and illustrate population-level effects of immunization. The global latitudinal patterns in outbreak seasonality could direct future studies of environmental and physiological drivers of disease transmission.
Effects of Degeneration on the Biphasic Material Properties of Human Nucleus Pulposus in Confined Compression

Study Design. The biphasic compressive material properties of normal and degenerate human nucleus pulposus tissue were measured in confined compression. Objectives. The objective of this study was to determine the effects of degeneration and age on the mechanical properties of human nucleus pulposus. Summary of Background Data. The nucleus pulposus exhibits swelling behavior in proportion to proteoglycan content. In shear, the nucleus exhibits both fluid-like and solid-like properties, suggesting a biphasic nature. To date, biphasic compressive properties of human nucleus pulpous have not been reported. Methods. Human nucleus pulposus samples were tested in confined compression. Isometric swelling stress and effective aggregate modulus were measured. Linear biphasic theory was used to determine the permeability of the tissue. Mechanical behavior was correlated with proteoglycan and water content. Results. Degeneration produced significant decreases in swelling stress (Psw = 0.138 ± 0.029 MPa nondegenerate, Psw = 0.037 ± 0.038 MPa degenerate) and effective aggregate modulus (HAeff = 1.01 ± 0.43 MPa nondegenerate, HAeff = 0.44 ± 0.19 MPa degenerate). Both properties were inversely correlated with proteoglycan content. Permeability increased with degeneration (ka = 0.9 ± 0.43 × 10−15 m4/N-s nondegenerate, ka = 1.4 ± 0.58 × 10−15 m4/N-s degenerate). Conclusions. Swelling is the primary load-bearing mechanism in both nondegenerate and degenerate nucleus pulposus. Knowledge of the biphasic material properties of the nucleus pulposus will aid the development of new treatment strategies for disc degeneration aimed at restoring mechanical function of the intervertebral disc.
In Search of a Euro Effect: Big Lessons from a Big Mac Meal?

We investigate whether the adoption of the euro was accompanied by an increase in prices in member countries, and whether it promoted goods market arbitrage in the form of faster convergence to a common price. By comparing the experience of eurozone countries to non-euro European countries in a ‘difference-in-differences’ specification we net out effects on prices unrelated to the euro. We conclude that (a) there is no evidence of significant price increases associated with the adoption of the euro even for food items; and (b) there is little systematic evidence of a significant improvement in goods market integration following the euro’s introduction.
The GRIN2B and GRIN2A Gene Variants Are Associated With Continuous Performance Test Variables in ADHD

Objective: To examine the association between variants of N-methyl-D-aspartate (NMDA) receptor subunit-encoding genes (GRIN2A and GRIN2B) and continuous performance test (CPT) variables in ADHD and healthy controls. Method: In all, 253 ADHD patients and 98 controls were recruited. The diagnosis, genotype, and diagnosis–genotype interaction effects for the CPT variables were examined. Results: Significant diagnosis effects were detected for all CPT variables. There were significant genotype and interaction effects on response time variability (RTV) by the GRIN2B variant. The C/C subgroup had higher RTV than the C/T + T/T subgroup in ADHD, but not in controls. There were significant genotype effects on omission errors by the GRIN2A variant. The G/G subgroup had more omission errors than the G/A + A/A subgroup in ADHD patients, but not in controls. Conclusion: These results suggest that the genetic variants of GRIN2B and GRIN2A confer an increased susceptibility to attentional impairment in ADHD patients.
Hypothetical Protein Avin_16040 as the S-Layer Protein of Azotobacter vinelandii and Its Involvement in Plant Root Surface Attachment

ABSTRACT A proteomic analysis of a soil-dwelling, plant growth-promoting Azotobacter vinelandii strain showed the presence of a protein encoded by the hypothetical Avin_16040 gene when the bacterial cells were attached to the Oryza sativa root surface. An Avin_16040 deletion mutant demonstrated reduced cellular adherence to the root surface, surface hydrophobicity, and biofilm formation compared to those of the wild type. By atomic force microscopy (AFM) analysis of the cell surface topography, the deletion mutant displayed a cell surface architectural pattern that was different from that of the wild type. Escherichia coli transformed with the wild-type Avin_16040 gene displayed on its cell surface organized motifs which looked like the S-layer monomers of A. vinelandii. The recombinant E. coli also demonstrated enhanced adhesion to the root surface.
Phenotypic severity of murine Plp mutants reflects in vivo and in vitro variatioans in transport of PLP isoproteins

Mutations of the major myelin gene, proteolipid protein (Plp), cause Pelizaeus‐Merzbacher disease and some forms of spastic paraplegia in man and dysmyelinating phenotypes in animals. The clinical severity is markedly heterogeneous, ranging from relatively mild to severe and fatal. Point mutations, or frame shifts, which are predicted to result in translation of structurally altered proteins account for many of these cases, including 3 of the allelic murine conditions. Plpjp‐rsh, Plpjp‐msd, and Plpjp represent an increasing severity of clinical and pathological phenotypes, respectively. In this study we determined whether there was any correlation between the severity of phenotype and the transport of the predicted abnormal protein. We examined the ability of the two products of the Plp gene, PLP and DM20, to insert into the plasma membrane of transfected BHK or COS‐7 cells, and into the myelin sheath of oligodendrocytes. With these complementary in vitro and in vivo approaches we find that proteins of Plpjp‐rsh, associated with the mildest phenotype, have a far greater ability to insert into the cell membrane or myelin than those associated with the severe phenotypes. Additionally, altered DM20 is more readily transported to the cell surface and to myelin than the PLP isoprotein. Interestingly, the two clonal cell lines chosen for transient transfection differ in their ability to fold DM20 from Plpjp‐rsh and Plpjp‐msd mice correctly, as inferred by staining for the conformation‐sensitive O10 epitope. In the case of Plpjp, which is associated with the most severe phenotype, no PLP or O10 staining is present at the cell surface or in myelin. The perturbation in trafficking observed for altered Plpjp PLP and DM20 in oligodendrocytes does not extend to other myelin membrane proteins, such as MAG and MOG, nor to wild type PLP co‐expressed in the same cell, all of which are correctly inserted into myelin. As Plp‐knockout mice do not have a dysmyelinating phenotype it seems unlikely that absence of PLP and/or DM20 in the membrane is responsible for the pathology. It remains to be determined whether the perturbation in protein trafficking is associated with the dysmyelination, or if the altered product of the mutant alleles acquire a novel function which is deleterious to myelin production by oligodendrocytes. GLIA 20:322–332, 1997. © 1997 Wiley‐Liss, Inc.
Teeth penetration force of the tiger shark Galeocerdo cuvier and sandbar shark Carcharhinus plumbeus.

This study examined the minimum force required of functional teeth and replacement teeth in the tiger shark Galeocerdo cuvier and the sandbar shark Carcharhinus plumbeus to penetrate the scales and muscle of sheepshead Archosargus probatocephalus and pigfish Orthopristis chrysoptera. Penetration force ranged from 7·7-41·9 and 3·2-26·3 N to penetrate A. probatocephalus and O. chrysoptera, respectively. Replacement teeth required significantly less force to penetrate O. chrysoptera for both shark species, most probably due to microscopic wear of the tooth surfaces supporting the theory shark teeth are replaced regularly to ensure sharp teeth that are efficient for prey capture.
FPP modulates mammalian sperm function via TCP‐11 and the adenylyl cyclase/cAMP pathway

Fertilization promoting peptide (FPP; pGlu‐Glu‐ProNH2), which is found in seminal plasma, promotes capacitation but inhibits spontaneous acrosome loss in mammalian spermatozoa in vitro. Adenosine, known to modulate the adenylyl cyclase (AC)/cAMP pathway, elicits these same responses whereas FPP + adenosine produces an enhanced response, leading to the hypothesis that FPP and adenosine modulate the same signal transduction pathway but act via different receptors. TCP‐11, the product of a t‐complex gene, is the putative receptor for FPP: Fab fragments of anti‐TCP‐11 antibodies have the same effect as FPP on mouse spermatozoa and Gln‐FPP, a competitive inhibitor of FPP, also competitively inhibits responses to the Fab fragments. In the present study, specific binding of 3H‐FPP to sperm membranes was significantly inhibited by 200 nM Gln‐FPP and anti‐TCP‐11 Fab fragments (1/25 dilution), thus confirming that FPP, Gln‐FPP, and Fab fragments compete for the same binding site. In addition, spermatozoa treated with A23187 to induce the acrosome reaction bound significantly less 3H‐FPP than untreated cells, suggesting that a large proportion of the FPP binding sites are associated with the acrosomal cap region; TCP‐11 is located in this region. In other experiments, 100 nM FPP significantly stimulated cAMP production in mouse sperm membranes, permeabilized cells and intact cells. Furthermore, Gln‐FPP inhibited production of cAMP in response to FPP but not to adenosine (10 μM) or its analogue NECA (100 nM), supporting the involvement of two different receptors. Finally, anti‐TCP‐11 Fab fragments (1/25 dilution) significantly stimulated cAMP production, whereas low Fab (1/200; nonstimulatory when used alone) plus adenosine (10 μM) significantly enhanced the stimulation of capacitation by adenosine. These results support the hypotheses that TCP‐11 is the receptor for FPP and that FPP↔TCP‐11 interactions modulate AC/cAMP. Mol. Reprod. Dev. 51:468–476, 1998. © 1998 Wiley‐Liss, Inc.
The in vivo neuron‐to‐astrocyte lactate shuttle in human brain: evidence from modeling of measured lactate levels during visual stimulation

Functional magnetic resonance spectroscopy (fMRS) allows the non‐invasive measurement of metabolite concentrations in the human brain, including changes induced by variations in neurotransmission activity. However, the limited spatial and temporal resolution of fMRS does not allow specific measurements of metabolites in different cell types. Thus, the analysis of fMRS data in the context of compartmentalized metabolism requires the formulation and application of mathematical models. In the present study we utilized the mathematical model introduced by Simpson et al. (2007) to gain insights into compartmentalized metabolism in vivo from the fMRS data obtained in humans at ultra high magnetic field by Mangia et al. (2007a) . This model simulates brain glucose and lactate levels in a theoretical cortical slice. Using experimentally determined concentrations and catalytic activities for the respective transporter proteins, we calculate inflow and export of glucose and lactate in endothelium, astrocytes, and neurons. We then vary neuronal and astrocytic glucose and lactate utilization capacities until close correspondence is observed between in vivo and simulated glucose and lactate levels. The results of the simulations indicate that, when literature values of glucose transport capacity are utilized, the fMRS data are consistent with export of lactate by neurons and import of lactate by astrocytes, a mechanism that can be referred to as a neuron‐to‐astrocyte lactate shuttle. A shuttle of lactate from astrocytes to neurons could be simulated, but this required the astrocytic glucose transport capacity to be increased by 12‐fold, and required that neurons not respond to activation with increased glycolysis, two conditions that are not supported by current literature.
Protective Role of Orthokeratology in Reducing Risk of Rapid Axial Elongation: A Reanalysis of Data From the ROMIO and TO-SEE Studies.

Purpose To determine the relative risk of rapid progression and number needed to treat (NNT) in younger and older children using combined data from the retardation of myopia in orthokeratology (ROMIO) and toric orthokeratology-slowing eye elongation (TO-SEE) studies. Methods Data from 136 subjects of two studies, ROMIO and TO-SEE, were retrieved (72 orthokeratology [ortho-k]: 37 ROMIO, 35 TO-SEE; 64 control: 41 ROMIO, 23 TO-SEE) and the myopia control effect on younger (6-8 years) and older (9-12 years) subjects evaluated. The rate of axial elongation was classified as not rapid (axial elongation = <0.36 mm/year) or rapid (axial elongation >0.36 mm/year). Results Cumulative frequency curves showed that the younger subjects in the control group had the greatest and most rapid axial elongation at the end of 24 months. In the younger subjects, ortho-k lens wear significantly reduced the risk of rapid progression by 88.8% (P = 0.002). The 2-year NNT for the younger ortho-k subgroup was 1.8, suggesting that treating just two younger subjects with ortho-k would prevent one subject from experiencing rapid progression over a 2-year period of treatment. The 2-year NNT for the older ortho-k subgroup was 11.8, which was statistically insignificant (P = 0.197). Conclusions Orthokeratology significantly reduced risk of rapid progression in younger subjects. Treating just two 6- to 8-year-old subjects with ortho-k instead of single-vision spectacles could prevent one subject from developing rapidly progressing axial elongation during this critical 2-year period.
Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza.

BACKGROUND Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown. METHODS The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age-de-escalation, adaptive design with a targeted systemic exposure. RESULTS From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0-8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9-11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12-23 months receiving the Food and Drug Administration-approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment. CONCLUSIONS The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9-11 months old is 3.5 mg/kg.
Isoflurane Modulation of Neuronal Nicotinic Acetylcholine Receptors Expressed in Human Embryonic Kidney Cells

Background: It is well established that neuronal nicotinic acetylcholine receptors (nAChRs) are sensitive to inhalational anesthetics. The authors previously reported that halothane potently blocked &agr;4&bgr;2-type nAChRs of rat cortical neurons. However, the effect of isoflurane, which is widely used clinically, on nAChRs largely remains to be seen. The authors studied the effects of isoflurane as compared with sevoflurane and halothane on the human &agr;4&bgr;2 nAChRs expressed in human embryonic kidney cells. Methods: The whole-cell and single-channel patch clamp techniques were used to record currents induced by acetylcholine. Results: Isoflurane, sevoflurane, and halothane suppressed the acetylcholine-induced currents in a concentration-dependent manner with 50% inhibitory concentrations of 67.1, 183.3, and 39.8 &mgr;m, respectively, which correspond to 0.5 minimum alveolar concentration or less. When anesthetics were coapplied with acetylcholine, isoflurane and sevoflurane decreased the apparent affinity of receptor for acetylcholine, but halothane, in addition, decreased the maximum acetylcholine current. When isoflurane was preapplied and coapplied, its inhibitory action was independent of acetylcholine concentration. Isoflurane blocked the nAChR in both resting and activated states. Single-channel analyses revealed that isoflurane at 84 &mgr;m decreased the mean open time and burst duration without inducing “flickering” during channel openings. Isoflurane increased the mean closed time. As a result, the open probability of single channels was greatly reduced by isoflurane. Conclusions: Isoflurane, sevoflurane, and halothane potently blocked the &agr;4&bgr;2 nAChR. Isoflurane suppression of whole-cell acetylcholine currents was a result of decreases in the open time, burst duration, and open probability and an increase in the closed time of single channels. The high sensitivity of neuronal nAChRs to inhalational anesthetics is expected to play an important role in several stages of anesthesia.
Application of force-length curve for determination of leg stiffness during a vertical jump.

PURPOSE The aim of this study was to present the methodology for estimation of a leg stiffness during a countermovement jump. The question was asked whether leg stiffness in the countermovement and take-off phases are similar to each other as demonstrated in previous reports. It was also examined whether the stiffness in left lower limb is similar to the one in right lower limb. METHODS The research was conducted on 35 basketball players. Each participant performed three countermovement jumps with arm swing to the maximum height. Measurements employed a Kistlerforce plate and a BTS SMART system for motion analysis. Leg stiffness (understood as an inclination of the curve of ground reaction forces vs. length) was computed for these parts of countermovement and take-off phases where its value was relatively constant and F(Δl) relationship was similar to linear. RESULTS Mean value (±SD) of total stiffness of both lower limbs in the countermovement phase was 7.1 ± 2.3 kN/m, whereas this value in the take-off phase was 7.5 ± 1 kN/m. No statistically significant differences were found between the leg stiffness in the countermovement and the take-off phases. No statistically significant differences were found during the comparison of the stiffness in the right and left lower limb. CONCLUSIONS The calculation methodology allows us to estimate the value of leg stiffness based on the actual shape of F(Δl) curve rather than on extreme values of ΔF and Δl. Despite different tasks of the countermovement and the take-off phases, leg stiffness in these phases is very similar. Leg stiffness during a single vertical jump maintains a relatively constant value in the parts with a small value of acceleration.
Ulysses Syndrome: The Modern-day Odyssey of Pediatric Patients With Uncomplicated Acute Appendicitis.

U lysses, the King of Ithaca, began his odyssey after being unwillingly recruited to fight in the Trojan War. Upon victory, he sailed for home to be reunited with his beloved wife, Penelope, and his son, Telemachus. What would have been a 3-week trip, turned into a 10-year ordeal filled with unexpected peril and ample misfortune. His unwavering desire to complete his journey or ‘‘nostos,’’ is the central theme of the tale. Ulysses syndrome, common, yet rarely discussed, is the medical phenomenon characterized by a series of physical and psychological disorders that follow the discovery of a false-positive result. Named after the Homeric protagonist, the syndrome is specifically used to describe a patient, who, despite being generally healthy at the onset of a medical evaluation, is subjected to the ordeal of repetitive laboratory testing, imaging, and unnecessary interventions, ultimately finding themselves back where they started with no diagnosis; possibly sustaining an avoidable iatrogenic injury and experiencing some degree of mental anguish along the way. Pediatric patients who present to the emergency department (ED) with vague abdominal pain may experience Ulysses syndrome when the search for a diagnosis results in findings concerning for uncomplicated acute appendicitis (UAA). In the past, such patients would be hydrated, observed for symptom resolution if clinical suspicion was low, or undergo an expeditious operation to remove an inflamed appendix. And sometimes, the surgeon would remove a ‘‘white’’ appendix. Because clinicians have been unable to accurately diagnose all cases of pediatric UAA, we have actively searched for methods to improve our accuracy and distinguish those patients we should take to the operating room from those we should not. Clinical decision rules and selective radiography have helped to reduce the negative appendectomy rates that once approached 10% for males and up to 30% for females, to less than 5% in recent years. Still, from time to time, we remove an uninflamed appendix and feel vanquished when we do. Although one could argue that the clinical examination done