Miracle-dz/UniFAR-FTUs huggingface dataset:
Optical laser trapping for studying the deformability of sickle red blood cells in response to hydroxyurea

Background: Sickle cell disease (SCD) is prevalent in Basrah city and affects the red blood cell (RBC) deformability and thereby causes disease symptoms. Hydroxyurea (HU) is effective in reducing morbidity and mortality in SCD patients by different mechanisms. Objectives: The aim of the study was to investigate the effect of HU on RBC deformability among SCD patients by direct laser optical trapping (OT) technique. Materials and Methods: Blood samples from SCD patients and control groups were prepared in the medical laboratory of Basrah Center for Hereditary Blood Diseases and transferred into physics laboratory wherein the laser system was presented and built-in. RBCs from each sample were exposed to three different powers of laser 5, 15, and 20 mW for 15 s and then were released and followed for 2 min. The images for each trapped RBC were obtained and at relaxation sequential times. The percentage changes in the diameters of trapped RBCs were measured for control and patient groups. Results: SCD patients were divided into two groups depending on whether they were receiving HU (39 patients) or not (43 patients). They were matched with 50 healthy individuals (control) regarding age and gender. We found that all the trapped RBCs were affected during the trapping time and then returned toward near normal with some differences between the groups and according to the power used. The deformability of HU group was better and closure to the control. Conclusion: The presented laser system and OT technique with optimal power are effective to study the RBC characteristics and deformability. HU is effective in improving RBC deformability among SCD patients.
LAN property for some fractional type Brownian motion

We study asymptotic expansion of the likelihood of a certain class of Gaussian processes characterized by their spectral density $f_\theta$. We consider the case where $f_\theta\PAR{x} \sim_{x\to 0} \ABS{x}^{-\al(\theta)}L_\theta(x)$ with $L_\theta$ a slowly varying function and $\al\PAR{\theta}\in (-\infty,1)$. We prove LAN property for these models which include in particular fractional Brownian motion %$B^\alpha_t,\: \alpha \geq 1/2$ or ARFIMA processes.
Echocardiographic Definition and Surgical Decision-Making in Unbalanced Atrioventricular Septal Defect: A Congenital Heart Surgeons' Society Multiinstitutional Study

Background— Although identification of unbalanced atrioventricular septal defect (AVSD) is obvious when extreme, exact criteria to define the limits of unbalanced are not available. We sought to validate an atrioventricular valve index (AVVI) (left atrioventricular valve area/total atrioventricular valve area, centimeters squared) as a discriminator of balanced and unbalanced forms of complete AVSD and to characterize the association of AVVI with surgical strategies and outcomes. Methods and Results— Diagnostic echocardiograms and hospital records of 356 infants with complete AVSD at 4 Congenital Heart Surgeons' Society (CHSS) institutions (2000–2006) were reviewed and AVVI measured (n=315). Patients were classified as unbalanced if AVVI≤0.4 (right dominant) or ≥0.6 (left dominant). Surgical strategy and outcomes were examined across the range of AVVI. Competing risks analysis until the time of commitment to a surgical strategy examined 4 end states: biventricular repair (BVR), univentricular repair (UVR), pulmonary artery banding (PAB), and death before surgery. A prediction nomogram for surgical strategy based on AVVI was developed. The majority of patients had balanced AVSD (0.4<AVVI<0.6) and underwent BVR. Patients with AVVI<0.19 uniformly underwent UVR. Heterogeneous repair strategies were found when 0.19≤AVVI≤0.39 (UVR and BVR), with a disproportionate number of deaths in this range. AVVI≥0.6 (left dominant) was less common. The proportion of subjects predicted for the end states at 12 months after diagnosis are: BVR, 86%; UVR, 7%; PAB, 1%; death without surgery, 1%; alive without surgery, 5%. Conclusions— AVVI effectively characterizes the transition between balanced and unbalanced AVSD with important correlation to anatomic substrate and selected surgical strategy.
Perceptions About Organ Donation Among African American, Hispanic, and White High School Students

We applied the Health Belief Model (HBM) to better understand perceptions of organ donation among African American, Hispanic, and White high school students. We conducted 14 focus groups with 18-year-old students to identify strategies to reach this audience when promoting the First-Person Consent Registry (FPCR) for organ donation. We found that African American, Hispanic, and White high school students are largely unaware of the need for organ donors, and are unfamiliar with how to join the FPCR. Participants identified more barriers to joining the FPCR than benefits. Two aspects of self-efficacy emerged related to joining the FPCR: decisional and task efficacy. Overall, few differences were found with respect to organ donation myths across the three ethnic groups. The results are discussed, with an emphasis on how the findings compare and contrast with previous organ donation research. We focus on message design and dissemination strategies for practitioners targeting 18-year-old high school students with organ donation promotional materials.
X-ray flares reveal mass and angular momentum of the Galactic Center black hole

We have analysed the light curve of the two brightest X-ray flares from the Galactic Center black hole, one flare observed by XMM-Newton on October 3, 2002 (Porquet et al. \cite{P2003}), and the other flare observed by Chandra on October 26, 2000 (Baganoff et al. \cite{B2001}). The power density spectra show five distinct peaks at periods of ˜100 s, 219 s, 700 s, 1150 s, and 2250 s common to both observations within their estimated measurement uncertainties. The power density spectrum of the recently reported infrared flare of June 16, 2003 (Genzel et al. \cite{Ge2003}) shows distinct peaks at two, if not three, periods (including the 1008 ± 120 s infrared period), which are consistent with the X-ray periods. The remaining two periods could not be covered by the infrared measurements. Each period can be identified with one of the characteristic gravitational cyclic modes associated with accretion disks, i.e. either Lense-Thirring precession, Kepler orbital motion and the vertical and radial epicyclic oscillation modes, in such a way that a consistent value for the black hole mass of MBH = 2.72 +0.12-0.19× 10 6 M⊙ and the angular momentum a = 0.9939 +0.0026-0.0074 is obtained. The available data on MBH derived from studies of the orbital motion of the S2 (S0-2) star (Schodel et al. \cite{S2002}; Ghez et al. \cite{Gh2003}) agree with our findings. Finally we discuss some implications of the fairly high value for the angular momentum.
The Akt signaling pathway contributes to postconditioning’s protection against stroke; the protection is associated with the MAPK and PKC pathways

We previously reported that ischemic postconditioning with a series of mechanical interruptions of reperfusion reduced infarct volume 2 days after focal ischemia in rats. Here, we extend this data by examining long‐term protection and exploring underlying mechanisms involving the Akt, mitogen‐activated protein kinase (MAPK) and protein kinase C (PKC) signaling pathways. Post‐conditioning reduced infarct and improved behavioral function assessed 30 days after stroke. Additionally, postconditioning increased levels of phosphorylated Akt (Ser473) as measured by western blot and Akt activity as measured by an in vitro kinase assay. Inhibiting Akt activity by a phosphoinositide 3‐kinase inhibitor, LY294002, enlarged infarct in postconditioned rats. Postconditioning did not affect protein levels of phosphorylated‐phosphatase and tensin homologue deleted on chromosome 10 or ‐phosphoinositide‐dependent protein kinase‐1 (molecules upstream of Akt) but did inhibit an increase in phosphorylated‐glycogen synthase kinase 3β, an Akt effector. In addition, postconditioning blocked β‐catenin phosphorylation subsequent to glycogen synthase kinase, but had no effect on total or non‐phosphorylated active β‐catenin protein levels. Furthermore, postconditioning inhibited increases in the amount of phosphorylated‐c‐Jun N‐terminal kinase and extracellular signal‐regulated kinase 1/2 in the MAPK pathway. Finally, postconditioning blocked death‐promoting δPKC cleavage and attenuated reduction in phosphorylation of survival‐promoting εPKC. In conclusion, our data suggest that postconditioning provides long‐term protection against stroke in rats. Additionally, we found that Akt activity contributes to postconditioning’s protection; furthermore, increases in εPKC activity, a survival‐promoting pathway, and reductions in MAPK and δPKC activity; two putative death‐promoting pathways correlate with postconditioning’s protection.
Perineural Invasion and Lymph Node Involvement as Indicators of Surgical Outcome and Pattern of Recurrence in the Setting of Preoperative Gemcitabine-Based Chemoradiation Therapy for Resectable Pancreatic Cancer

Objective:To analyze the histopathological indicators significantly associated with surgical outcome and the pattern of recurrence in the setting of preoperative gemcitabine-based chemoradiation therapy (CRT) and subsequent pancreatectomy. Background:Clinicopathological assessment of the resected specimen is an indispensable tool for predicting patient prognosis and localizing high-risk sites for tumor relapse. This procedure is also essential for the establishment of efficient postoperative follow-up protocols in the setting of a preoperative CRT strategy. Methods:In a prospective phase II clinical trial at our hospital, 110 patients received preoperative CRT and subsequent resection. All 110 resected cases were included in this study. We employed disease-free survival (DFS) as a surgical outcome, and the pattern of recurrence was divided into 2 categories: (1) recurrence in the abdominal cavity (RAC), defined as either a locoregional or a peritoneal recurrence; or (2) distant recurrence (DR), defined as cancer recurrence in a distant organ. Clinicopathological variables were analyzed in association with DFS, RAC, and DR. Results:Positive nodal involvement and perineural invasion were independent factors that were significantly associated with an unfavorable DFS (P = 0.021 and P = 0.026, respectively). The presence of perineural invasion was the single independent variable significantly associated with an increased risk of RAC (P = 0.002), whereas the status of nodal involvement was the single independent variable significantly associated with an increased risk of DR (P = 0.013). Conclusions:The status of nodal involvement and perineural invasion in resected specimens are significantly associated with DFS and clearly predict the pattern of recurrence in the setting of a preoperative gemcitabine-based CRT strategy. This study is registered at UMIN-CTR and carries the ID number UMIN000001804.
The Effects of Theta and Gamma tACS on Working Memory and Electrophysiology

A single blind sham-controlled study was conducted to explore the effects of theta and gamma transcranial alternating current stimulation (tACS) on offline performance on working memory tasks. In order to systematically investigate how specific parameters of tACS affect working memory, we manipulated the frequency of stimulation (theta frequency vs. gamma frequency), the type of task (n-back vs. change detection task) and the content of the tasks (verbal vs. figural stimuli). A repeated measures design was used that consisted of three sessions: theta tACS, gamma tACS and sham tACS. In total, four experiments were conducted which differed only with respect to placement of tACS electrodes (bilateral frontal, bilateral parietal, left fronto-parietal and right-fronto parietal). Healthy female students (N = 72) were randomly assigned to one of these groups, hence we were able to assess the efficacy of theta and gamma tACS applied over different brain areas, contrasted against sham stimulation. The pre-post/sham resting electroencephalogram (EEG) analysis showed that theta tACS significantly affected theta amplitude, whereas gamma tACS had no significant effect on EEG amplitude in any of the frequency bands of interest. Gamma tACS did not significantly affect working memory performance compared to sham, and theta tACS led to inconsistent changes in performance on the n-back tasks. Active theta tACS significantly affected P3 amplitude and latency during performance on the n-back tasks in the bilateral parietal and right-fronto parietal protocols.
Tumor Directed, Scalp Sparing Intensity Modulated Whole Brain Radiotherapy for Brain Metastases

Despite significant technical advances in radiation delivery, conventional whole brain radiation therapy (WBRT) has not materially changed in the past 50 years. We hypothesized that IMRT can selectively spare uninvolved brain and scalp with the goal of reducing acute and late toxicity. MRI/CT simulation image registration was performed. We performed IMRT planning to simultaneously treat the brain tumor(s) on MRI + 5 mm margin to 37.5 Gy in 15 fractions while limiting the uninvolved brain + 2 mm margin to 30 Gy in 15 fractions and the mean scalp dose to #18 Gy. Three field IMRT plans were compared to conventional WBRT plans. Symptomatic patients were started on conventional WBRT for 2 to 3 fractions while IMRT planning was performed. Seventeen consecutive patients with brain metastases with RPA class I and II disease with no leptomeningeal spread were treated with IMRT WBRT. Compared to conventional WBRT, IMRT reduced the mean scalp dose (26.2 Gy vs. 16.4 Gy, p < 0.001) and the mean PTV30 dose (38.4 Gy vs. 32.0 Gy, p < 0.001) while achieving similar mean PTV37.5 doses (38.3 Gy vs. 38.0 Gy, p = 0.26). Using Olsen hair loss score criteria, 4 of 15 assessable patients preserved at least 50% of hair coverage at 1 to 3 months after treatment while 6 patients preserved between 25 and 50% hair coverage. At a median follow-up of 6.8 months (range: 5 to 15 months), the median overall survival was 5.4 months. Four patients relapsed within the brain, one within the PTV37.5 and three outside the PTV37.5. Tumor directed, scalp sparing IMRT is feasible, achieves rational dose distributions and preserves partial hair coverage in the majority of patients. Further studies are warranted to determine whether the increased utilization of resources needed for IMRT are appropriate in this setting.
PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics.

BACKGROUND Programmed cell death ligand 1 (PD-L1) is a cell surface molecule that plays a critical role in suppressing immune responses, mainly through binding of the PD-1 receptor on T lymphocytes. PD-L1 may be expressed by metastatic melanoma (MM). However, its clinical and biological significance remains unclear. Here, we investigated whether expression of PD-L1 in MM identifies a biologically more aggressive form of the disease, carrying prognostic relevance. PATIENTS AND METHODS PD-L1 expression was analyzed by immunohistochemistry using two different antibodies in primary tumors and paired metastases from 81 melanoma patients treated at a single institution. Protein expression levels were correlated with PD-L1 mRNA, BRAF mutational status and clinical outcome. PD-L1(+) and PD-L1(-) subsets of the A375 cell line were stabilized in vitro and compared using gene expression profiling and functional assays. Results were confirmed using xenograft models. RESULTS PD-L1 membrane positivity was detected in 30/81 (37%) of patients. By multivariate analysis, Breslow thickness and PD-L1 membrane positivity were independent risk factors for melanoma-specific death {PD-L1 5% cutoff [hazard ratio (HR) 3.92, confidence interval (CI) 95% 1.61-9.55 P < 0.003], PD-L1 as continuous variable (HR 1.03, 95% CI 1.02-1.04 P < 0.002)}. PD-L1 expression defined a subset of the BRAF-mutated A375 cell line characterized by a highly invasive phenotype and by enhanced ability to grow in xenograft models. CONCLUSIONS PD-L1 is an independent prognostic marker in melanoma. If confirmed, our clinical and experimental data suggest that PD-L1(+) melanomas should be considered a disease subset with distinct genetic and morpho-phenotypic features, leading to enhanced aggressiveness and invasiveness.
Evaluation of a cardiovascular disease opportunistic risk assessment pilot ('Heart MOT' service) in community pharmacies.

BACKGROUND Cardiovascular risk-based screening is proposed as a key intervention to reduce premature cardiovascular disease (CVD) in the UK and internationally. This study evaluated a targeted cardiovascular (CVD) assessment pilot in 23 community pharmacies in Birmingham, UK. METHODS The CVD risk assessment service used near-patient testing and the Framingham risk equations administered by pharmacists to screen clients aged 40-70 without known CVD. Outcomes assessed included volume of activity, uptake by deprivation and ethnicity and onwards referral. RESULTS Complete data were available for 1130 of 1141 clients; 679 (60%) male, 218 (19%) smokers and 124 (11%) had a family history of CVD. Overall, 792 (70%) of clients were referred to their general practice: 201 (18%) at CVD risk of 20% or more, remainder with individual risk factor(s). Greater representation from Black (7.4%) and Asian (24.8%) communities and from average and less deprived quintiles than the affluent and most deprived was observed. CONCLUSIONS Community pharmacies can provide a CVD risk assessment service in a UK urban setting that can attract males and provide access for deprived communities and Black and Asian communities. A pharmacy service can support GP practices in identifying and managing the workload of around 30% of clients.
Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children

A double-blind placebo trial was conducted to determine the effect of moderate to high loads of Trichuris trichiura (whipworm) infection on the cognitive functions of 159 school children (age 9–12 years) in Jamaica. Infected children were randomly assigned to Treatment or Placebo groups. A third group of randomly selected uninfected children were assigned to a Control for comparative purposes. The improvement in cognitive function was evaluated using a stepwise multiple linear regression, designed to control for any confounding variables. The expulsion of worms led to a significant improvement in tests of auditory short-term memory (P < 0.02; P < 0.01), and a highly significant improvement in the scanning and retrieval of long-term memory (P < 0.001). After 9 weeks, treated children were no longer significantly different from an uninfected Control group in these three tests of cognitive function. The removal of T. trichiura was more important than Ascaris lumbricoides in determining this improvement. The results suggest that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy.
Basal and Src kinase‐mediated activation of the EphA2 promoter requires a cAMP‐responsive element but is CREB‐independent

We have previously identified the EphA2 receptor tyrosine kinase as a potentially important injury‐responsive gene and a transcriptional target of Src kinase activity in renal ischemia‐reperfusion injury (IRI). In the present study, we confirmed, using EphA2 gene trap mice that the endogenous EphA2 promoter is strongly activated following renal IRI. We also examined in more detail the mechanisms responsible for Src kinase‐induced activation of the −2 kb human EphA2 promoter and found that the minimal Src‐responsive elements were contained in the −145 to +137 region of the human EphA2 gene. This region contains a canonical cAMP‐responsive element (CRE) that we found to be critical for both basal and Src kinase‐induced transcriptional activity. However, despite activation of the prototypical CRE‐binding factor CREB by the Src kinase Fyn, siRNA‐mediated knockdown of CREB had no significant impact on either basal or Fyn‐induced EphA2 promoter activity. Similarly, activation of CREB by the adenylate cyclase agonist forskolin failed to induce EphA2 promoter activation. Thus, Src kinase‐induced activation of the EphA2 promoter is CRE‐dependent but CREB‐independent. J. Cell. Biochem. 112: 1268–1276, 2011. © 2011 Wiley‐Liss, Inc.
Roller Coaster Scanning reveals spontaneous triggering of dendritic spikes in CA1 interneurons

Inhibitory interneurons are considered to be the controlling units of neural networks, despite their sparse number and unique morphological characteristics compared with excitatory pyramidal cells. Although pyramidal cell dendrites have been shown to display local regenerative events—dendritic spikes (dSpikes)—evoked by artificially patterned stimulation of synaptic inputs, no such studies exist for interneurons or for spontaneous events. In addition, imaging techniques have yet to attain the required spatial and temporal resolution for the detection of spontaneously occurring events that trigger dSpikes. Here we describe a high-resolution 3D two-photon laser scanning method (Roller Coaster Scanning) capable of imaging long dendritic segments resolving individual spines and inputs with a temporal resolution of a few milliseconds. By using this technique, we found that local, NMDA receptor-dependent dSpikes can be observed in hippocampal CA1 stratum radiatum interneurons during spontaneous network activities in vitro. These NMDA spikes appear when approximately 10 spatially clustered inputs arrive synchronously and trigger supralinear integration in dynamic interaction zones. In contrast to the one-to-one relationship between computational subunits and dendritic branches described in pyramidal cells, here we show that interneurons have relatively small (∼14 μm) sliding interaction zones. Our data suggest a unique principle as to how interneurons integrate synaptic information by local dSpikes.
Functional outcomes of fungal community shifts driven by tree genotype and spatial‐temporal factors in Mediterranean pine forests

Fungi provide relevant ecosystem services contributing to primary productivity and the cycling of nutrients in forests. These fungal inputs can be decisive for the resilience of Mediterranean forests under global change scenarios, making necessary an in-deep knowledge about how fungal communities operate in these ecosystems. By using high-throughput sequencing and enzymatic approaches, we studied the fungal communities associated with three genotypic variants of Pinus pinaster trees, in 45-year-old common garden plantations. We aimed to determine the impact of biotic (i.e., tree genotype) and abiotic (i.e., season, site) factors on the fungal community structure, and to explore whether structural shifts triggered functional responses affecting relevant ecosystem processes. Tree genotype and spatial-temporal factors were pivotal structuring fungal communities, mainly by influencing their assemblage and selecting certain fungi. Diversity variations of total fungal community and of that of specific fungal guilds, together with edaphic properties and tree's productivity, explained relevant ecosystem services such as processes involved in carbon turnover and phosphorous mobilization. A mechanistic model integrating relations of these variables and ecosystem functional outcomes is provided. Our results highlight the importance of structural shifts in fungal communities because they may have functional consequences for key ecosystem processes in Mediterranean forests.