Miracle-dz/UniFAR-FTUs huggingface dataset:
Segmenting subregions of the human hippocampus on structural magnetic resonance image scans: An illustrated tutorial

Background: The hippocampus plays a central role in cognition, and understanding the specific contributions of its subregions will likely be key to explaining its wide-ranging functions. However, delineating substructures within the human hippocampus in vivo from magnetic resonance image scans is fraught with difficulties. To our knowledge, the extant literature contains only brief descriptions of segmentation procedures used to delineate hippocampal subregions in magnetic resonance imaging/functional magnetic resonance imaging studies. Methods: Consequently, here we provide a clear, step-by-step and fully illustrated guide to segmenting hippocampal subregions along the entire length of the human hippocampus on 3T magnetic resonance images. Results: We give a detailed description of how to segment the hippocampus into the following six subregions: dentate gyrus/Cornu Ammonis 4, CA3/2, CA1, subiculum, pre/parasubiculum and the uncus. Importantly, this in-depth protocol incorporates the most recent cyto- and chemo-architectural evidence and includes a series of comprehensive figures which compare slices of histologically stained tissue with equivalent 3T images. Conclusion: As hippocampal subregion segmentation is an evolving field of research, we do not suggest this protocol is definitive or final. Rather, we present a fully explained and expedient method of manual segmentation which remains faithful to our current understanding of human hippocampal neuroanatomy. We hope that this ‘tutorial’-style guide, which can be followed by experts and non-experts alike, will be a practical resource for clinical and research scientists with an interest in the human hippocampus.
Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer.

603 Background: While most patients with breast cancer receiving neoadjuvant chemotherapy (NCT) have some tumor response, a small proportion progress during therapy. Although several groups have looked at markers for response, none have specifically evaluated markers for progression. The goal of this study was to identify predictors of tumor progression during NCT with the ultimate aim of identifying the subset of patients who may benefit from a first-line surgical approach. METHODS Patients with stage I-III breast cancer treated at a single comprehensive cancer center with NCT between 1994 and 2007 were included. Data was obtained from a review of medical records of patients in a prospectively acquired database. Chemotherapy consisted of anthracycline and/or taxane-based regimens. Statistical analysis was performed using univariate and multivariate analysis with logistic regression analyzing patients with some response or stable disease versus patients with progression. RESULTS 1928 patients received NCT: 1762 (91%) had some response (minor, partial, or complete), 107 (6%) had stable disease (SD), and 59 (3%) progressed (PD) on at least one NCT regimen. Clinical factors that correlate with PD in univariate analysis include presenting T (T3 vs T1, p = 0.002) and AJCC stage (stage IIIb/IIIc vs I/II/III, p = 0.02). Predictive histopathological features were high tumor grade (p = 0.005), high Ki-67 (p = 0.002), and negative ER and PR status (p < 0.0001 and p = 0.0006). Patients with PD were more likely to be treated with a taxane (79% vs 88%, p = 0.04). In the post-NCT surgical specimens, patients with PD were more likely to have higher T stage (p < 0.0001), lymph node metastasis (p = 0.01), and lymphovascular invasion (p = 0.02). On multivariate analysis, pre-NCT T status and ER status were the most important predictors of progression. CONCLUSIONS Pre-treatment characteristics predictive of disease progression on NCT include advanced tumors, high tumor grade, high Ki-67, and negative ER or PR status. Since high grade and negative ER/PR status have also been associated with a complete pathologic response to NCT, there is a clear need for more specific molecular predictors of response and progression in order to select appropriate treatment in these patients. No significant financial relationships to disclose.
Accumulation and Conversion of Sugars by Developing Wheat Grains : VI. Gradients Along the Transport Pathway from the Peduncle to the Endosperm Cavity during Grain Filling.

Gradients along the transport pathway from the peduncle to the endosperm cavity were examined during grain filling in wheat. Sieve tube exudate was collected from severed aphid stylets established on the peduncle and rachis and on the vascular bundles in the creases of grains. Phloem exudate could also be collected from broken grain pedicels, and by puncturing the vascular bundle in the grain crease with a needle. Stylets on excised grains persisted exuding, indicating that grain sieve tubes are capable of loading solutes. There was little, if any, discernible gradient in osmolality or solute composition (sucrose, total amino acids) of sieve tube contents along the phloem pathway from the peduncle to the rachis or along the rachis itself. Neither was a gradient detected in osmolality along the sieve tube pathway from the rachis through the rachilla and grain stalk to the crease. Demonstrable solute gradients occurred only across those tissues of the grain crease between the crease sieve tubes and the endosperm cavity, a distance of just 1 millimeter. However, while the sucrose concentration in the sieve tubes was almost tenfold that in the endosperm cavity sap, total amino acids were only threefold higher, and the potassium concentrations of the two were equal. Our observations strongly implicate the movement of assimilates from the sieve tubes and across the crease tissues as important control points in grain filling.
Bladder function after incomplete spinal cord injury in mice: quantifiable outcomes associated with bladder function and efficiency of dehydroepiandrosterone as a therapeutic adjunct.

OBJECT The authors conducted a study to establish outcomes associated with bladder function in a mouse model of spinal cord injury (SCI) and to assess the sensitivity of these outcomes in determining the efficacy of pharmacological treatments. METHODS A mouse model of moderate contusive SCI was used. Outcome parameters included physiological, behavioral, and morphological measurements. To test the sensitivity of these outcomes, the authors used a dehydroepiandrosterone (DHEA) treatment that they had previously shown to promote neurological recovery effectively after SCI. A behavioral scale was used to identify the day at which autonomic function of the bladder was recovered. The reduction in the daily volume of urine during the period of functional recovery paralleled this scale. They then determined the day postinjury at which the functional differences between the vehicle- and DHEA-treated mice exhibited the maximal amplitude. Changes were measured in the composition of the extracellular matrix relative to collagen expression in the layer muscularis of the detrusor at this time point. They found that SCI increases the ratio of collagen type III to collagen type I in the detrusor. Moreover, in the DHEA-treated group, this ratio was similar to that demonstrated in sham-operated mice, establishing the sensitivity of this outcome to assess therapeutic benefits to the bladder function. They next examined the relationship between measurements of neurological recovery and controlled voiding by using cluster analysis. CONCLUSIONS The authors found that early recovery of controlled voiding is predictive of motor recovery.
Incidence of and risk factors for type-specific anal human papillomavirus infection among HIV-positive MSM

Objective:HIV-positive MSM are at increased risk of anal human papillomavirus (HPV) infection compared with men in the general population, and little is known about the natural history of anal HPV infection in this population. The objective of this study was to determine the incidence of and risk factors for anal type-specific HPV infection. Design:Prospective cohort study. Methods:HIV-positive MSM were evaluated for anal HPV DNA, lifestyle factors, and sexual risk behaviors every 6 months for at least 2 years. Results:The overall incidence rate of detectable type-specific anal HPV infection was 21.3 per 100 person-years [95% confidence interval (CI) 17.7–25.4] and was 13.3/100 person-years (10.5–16.6) for oncogenic HPV types. The most common incident infections were HPV 18 (3.7/100 person-years) and HPV 16 (3.5/100 person-years). An increased number of recent partners with whom the participant was the receptive partner [odds ratio (OR) 2.9 (1.6–5.1) 8+ partners vs. 0–1], an increased number of new partners in which the participant was the receptive partner [OR 1.03 (1.01–1.1) per partner], an increased number of new oral–anal contact partners in which the participant was the receptive partner [OR 1.1 (1.03–1.1) per partner], and the frequency of receptive anal intercourse [OR 1.1 (1.03–1.1) per act] all significantly increased the odds of incident HPV infection (P ⩽ 0.05). Conclusion:HIV-positive MSM have a high incidence of oncogenic anal HPV infection. Recent receptive anal sexual behaviors, including receptive anal intercourse and receptive oral–anal contact, are the most important risk factors for incident anal HPV infection.
`Turned into Taxpayers': Paraplegia, Rehabilitation and Sport at Stoke Mandeville, 1944-56

This article explores the links between rehabilitation practices and the aims of successive postwar British governments between 1944 and 1956. It focuses on the work at Stoke Mandeville Hospital in Aylesbury where rehabilitation centred around sporting activity. While games and sport were important at the hospital, they were seen more as a means to an end outside the gates of the institution. The focus for the state was labour and the article argues that the process of rehabilitation through sport was informed by the demands of central government and the desire to reduce the economic burden of numbers of permanently disabled people.
Rescheduling a permutation flowshop problems under the arrival a new set of jobs

A set of jobs has been scheduled on a machine flowhop, but not yet processed, when a set of new jobs arrives. The problem of shop rescheduling on occurrence of an unforeseen disruption is addressed here. The decision maker needs to insert the new jobs into the existing schedule without excessively changing it. The practical solution requires satisfaction of two often conflicting goals. We propose a method to heuristically obtain a satisfying production schedule. The procedure involves two stages. In a first step, given a fixed order of jobs a conventional heuristic is proposed to successively assign the jobs to the machines. In a second one. the simulated annealing is applied to optimise the order of the jobs.
Differential gene expression profile of human tonsil high endothelial cells: implications for lymphocyte trafficking

Lymphocyte recirculation is dependent on the interactions of adhesion and signaling molecules expressed on lymphocytes and their partners on high endothelial cells (HEC). Many of the events in this process have yet to be molecularly characterized. To identify novel HEC‐specific proteins with potential function in the recruitment cascade, we sequenced a normalized human tonsil HEC cDNA library (generated from an inflamed tonsil) from which lymphocyte and human umbilical vein endothelial cell cDNAs had een subtracted. One‐thousand forty‐nine sequences were analyzed. All but three mapped to known cDNAs or genomic DNAs. The two most abundant transcripts encoded α2‐macroglobulin and hevin. The next‐abundant transcripts encoded several other protease inhibitors, making this protein class the most prominent in HEC. Several endothelial‐specific transcripts were also identified, including those encoding E‐selectin, vascular cell adhesion molecule‐1, vascular endothelial‐junctional adhesion molecule, and platelet‐endothelial cell adhesion molecule‐1. The library contains a great diversity of transcripts, and studies of the encoded proteins will provide further insight into the complex biology of these specialized endothelial cells.
Chemical castration and anti‐androgens induce differential gene expression in prostate cancer

Endocrine therapy by castration or anti‐androgens is the gold standard treatment for advanced prostate cancer. Although it has been used for decades, the molecular consequences of androgen deprivation are incompletely known and biomarkers of its resistance are lacking. In this study, we studied the molecular mechanisms of hormonal therapy by comparing the effect of bicalutamide (anti‐androgen), goserelin (GnRH agonist) and no therapy, followed by radical prostatectomy. For this purpose, 28 men were randomly assigned to treatment groups. Freshly frozen specimens were used for gene expression profiling for all known protein‐coding genes. An in silico Bayesian modelling tool was used to assess cancer‐specific gene expression from heterogeneous tissue specimens. The expression of 128 genes was > two‐fold reduced by the treatments. Only 16% of the altered genes were common in both treatment groups. Of the 128 genes, only 24 were directly androgen‐regulated genes, according to re‐analysis of previous data on gene expression, androgen receptor‐binding sites and histone modifications in prostate cancer cell line models. The tumours containing TMPRSS2–ERG fusion showed higher gene expression of genes related to proliferation compared to the fusion‐negative tumours in untreated cases. Interestingly, endocrine therapy reduced the expression of one‐half of these genes and thus diminished the differences between the fusion‐positive and ‐negative samples. This study reports the significantly different effects of an anti‐androgen and a GnRH agonist on gene expression in prostate cancer cells. TMPRSS2‐ERG fusion seems to bring many proliferation‐related genes under androgen regulation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Antidiabetic activity of alkaloids of Aerva lanata roots on streptozotocin-nicotinamide induced type-II diabetes in rats

Abstract Context: The roots of Aerva lanata Linn. (Amaranthaceae) (AL) are employed traditionally as an antihyperglycaemic in the Ayurvedic system of medicine. Objective: The present investigation is focus for identification and isolation of the bioactive compound from methanol roots extract of AL against streptozocin-nicotinamide induced elevated serum glucose level in rats. Materials and methods: The methanol extract of the roots was fractionated using different solvents. The partially purified alkaloid basified toluene fraction (PPABTF) showed the presence of alkaloids. The fraction (10 and 20 mg/kg) was tested for oral glucose tolerance test (OGTT) and in non-insulin-dependent diabetes mellitus (NIDDM)-induced elevated serum glucose level in rats. The fraction was also subjected to high performance thin layer chromatography (HPTLC) for the determination of content of individual alkaloids. Results: Single oral administration of PPABTF (10 and 20 mg/kg) after 20 h caused a significant (p < 0.01) reduction in the serum glucose level (mg/dl). On other hand, PPABTF normalised plasma glucose levels after 2 weeks of repeated oral administration in diabetic rats (p < 0.01). HPTLC analysis on PPABTF showed the presence of three known alkaloids. The fraction was further subjected to column chromatography and the compounds identified by ultraviolet, infrared, mass spectroscopy and nuclear magnetic resonance, as canthin-6-one derivatives. Conclusion and discussion: The PPABTF in the dose of 20 mg/kg showed significant effects on streptozotocin-nicotinamide induced type-II NIDDM in rats. The activity may be due to the presence of alkaloids like canthin-6-one derivatives.
Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals.

CONTEXT Due to its good correlation to glycemic clamp, HOMA-IR has been widely utilized as insulin resistance index in clinical and epidemiological studies involving non-alcoholic fatty liver disease carriers. However, values used for this parameter have shown large variability. OBJECTIVE To identify the HOMA-IR cut value that best distinguishes non-diabetic non-alcoholic fatty liver disease patients from a control group. METHODS One hundred sixteen non-alcoholic fatty liver disease patients were studied, diagnosed by clinical, biochemical, and liver image or biopsy criteria, and 88 healthy individuals, without any liver disease and testing for oral glucose tolerance within normality. These groups did not differ in age and gender. All were submitted to oral glucose tolerance test and blood samples were collected for glucose and insulin measurements by immunofluorometric method. HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. RESULTS NAFLD patients showed higher insulin, glycemia, and HOMA-IR values than control group, even when excluding glucose intolerant and diabetes mellitus patients by their glycemic curves. HOMA-IR 75th percentile for control group was 1.78 and the best area under the curve index was obtained for HOMA-IR values of 2.0 [AUC= 0.840 (0.781-0.899 CI 95%), sensitivity (Se): 85%, specificity (Sp): 83%] while value 2.5 showed best specificity without important loss in sensitivity [AUC=0,831 (0.773-0.888) Se = 72%, Sp = 94%]. CONCLUSION HOMA-IR values above or equal to 2.0 or 2.5 show enhanced diagnostic value in distinguishing non-alcoholic fatty liver disease carriers from control group individuals.
Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression

Background: Histone deacetylase (HDAC), a host mediator of gene repression, inhibits HIV gene expression and virus production and may contribute to quiescence of HIV within resting CD4 T cells. Objectives: To test the ability of valproic acid (VPA), an inhibitor of HDAC in clinical use, to induce expression of HIV from resting CD4 T cells. Methods: Chromatin immunoprecipitation measured the capability of VPA to deacetylate the HIV promoter, a remodeling of chromatin linked to gene expression. The effect of VPA on resting CD4 T cell phenotype was measured by flow cytometric analysis, and its effect on de novo HIV infection of peripheral blood mononuclear cells was measured ex vivo. Outgrowth of HIV from resting CD4 T cells of aviremic, HIV-infected donors treated with highly active antiretroviral therapy was compared in limiting-dilution cultures after mitogen stimulation or exposure to VPA. Results: VPA induced acetylation at the integrated HIV proviral promoter, but CD4 cells exposed to VPA did not become activated or more permissive for de novo HIV infection. VPA induced outgrowth of HIV from the resting CD4 cells of aviremic patients at concentrations achievable in vivo as frequently as did mitogen stimulation. Conclusions: With advances in antiretroviral therapy, HIV infection might be cleared by intensive time-limited treatment coupled with practical strategies that disrupt latency without enhancing new infection. HDAC inhibitors are capable of inducing expression of quiescent provirus, without fully activating cells or enhancing de novo infection, and may be useful in future clinical protocols that seek to eradicate HIV infection.
Comparison of Two Combined Bioelectrochemical and Sulfur Autotrophic Denitrification Processes for Drinking Water Treatment

Abstract Two combined bioelectrochemical and sulfur autotrophic denitrification (CBSAD) processes for the treatment of nitrate contaminated drinking water were studied in this article, the main difference between the two processes was whether the limestone was packed in the reactor. In these processes, the sulfur denitrification was carried out in the lower part (Sulfur Part) of the reactors while the bioelectrochemical hydrogen denitrification in the upper part (Bioelectrochemical Part). Sulfur Part of one reactor was packed with elemental sulfur and limestone while no limestone was packed in Sulfur Part of the other, the former reactor is referred to as RSL and the latter as RS. The denitrification results of the two reactors were compared under different conditions, from which it can be concluded that the minimum current of RSL was about 2 mA higher than that of RS. However, at the same hydraulic retention time (HRT) and minimum current, the nitrate removal of both reactors was higher than 90% while no nitrite was accumulated in the effluent. Ca2+ concentration in Sulfur Part effluent of RSL was increased because of the packed limestone, which led to the requirement of Ca2+ removal in Bioelectrochemical Part. The effluent sulfate concentration of RSL was higher than that of RS. When current was lower than 3 mA, the effluent pH value of RSL was about 0.6 higher than that of RS. However, the effluent pH of two parts of both reactors was about neutral under optimum operation conditions. The optimum operation condition of RSL was 1.9–4 h HRT under 1.5–14 mA minimum current, while that of RSL was 1.9–5 h under 3–16.5 mA. The effluent quality of RS was better than that of RSL.
Assessment of complex mental activity across the lifespan: development of the Lifetime of Experiences Questionnaire (LEQ)

Background. Brain reserve is a property of the central nervous system related to complex mental activity which may mediate the course and clinical expression of brain injury. Since there is no instrument that comprehensively assesses complex mental activity through the lifespan, we developed and tested the Lifetime of Experiences Questionnaire (LEQ) in a prospective study of healthy ageing. Method. The LEQ assesses educational, occupational and cognitive lifestyle activities at different stages through life. Test–retest, item analysis and Item Response Theory (IRT) were used to determine reliability. Dimensionality was evaluated using factor analysis. Validity was established through IRT analysis of test performance, correlation with an extant contemporaneous instrument (Cognitive Activities Scale; CAS) and prediction of global cognitive change over 18 months controlling for age, baseline cognition and hypertension. Results. In a sample of healthy older individuals (n=79) the LEQ was found to be consistent, coherent and discriminate between individuals with high and low mental activity levels. Factor analysis revealed a dominant factor which loaded heavily on education, occupation and leisure activity. Total LEQ was significantly correlated with the CAS. Furthermore, individuals with higher LEQ scores showed less cognitive decline over 18 months, independent of covariates (r=0·37, p=0·003). Conclusions. The LEQ is a reliable and valid instrument for assessing complex lifespan mental activity which is protective against cognitive decline. The LEQ is therefore proposed as a useful tool for estimating brain reserve in older individuals and further development is anticipated.