Miracle-dz/UniFAR-FTUs huggingface dataset:
The replacement of ‘paper’ cases by interactive online virtual patients in problem-based learning

St George's University of London (SGUL) has a Problem-Based Learning (PBL) curriculum for its undergraduate medicine course, using traditional paper-based patient cases. To counter the limitation that paper cases are linear and do not allow students to explore the consequences of decisions, interactive online virtual patients (VPs) were developed which allowed students to consider options as the cases unfold, and allow students to explore the consequences of their actions. A PBL module was converted to VPs, and delivered to 72 students in 10 tutorial groups, with 5 groups each week receiving VPs with options and consequences, and 5 groups receiving online VPs but without options. A comprehensive evaluation was carried out, using questionnaires, and interviews.Both tutors and students believed that the ability to explore options and consequences created a more engaging experience and encouraged students to explore their learning. They regretted the loss of paper and neither group could see any value in putting cases online without the options. SGUL is now adapting its transitional year between the early campus years and the clinical attachment years. This will include the integration of all technology-based resources with face-to-face learning and create a more adaptive, personalised, competency-based style of learning.
Effects of Left Inferior Prefrontal Stimulation on Episodic Memory Formation: A Two-Stage fMRIrTMS Study

Successful recovery of words from episodic memory relies strongly on semantic processes at the time of encoding. Evidence from several functional magnetic resonance imaging (fMRI) studies has shown that changes in neural activity in the left inferior prefrontal cortex (LIPFC) during semantic encoding predict subsequent memory performance. This evidence has been taken to suggest that LIPFC plays a critical role in memory formation. Functional neuroimaging findings, however, do not establish a causal brain-behavior relationship. To determine whether there is a causal link between LIPFC involvement at encoding and subsequent success in memory performance, we conducted a two-part study in which we first used fMRI to localize encoding-related activation in LIPFC and then employed repetitive transcranial magnetic stimulation (rTMS) to manipulate neural processes in LIPFC during semantic encoding. To demonstrate the neuroanatomical specificity of any observed effect and to control for nonspecific rTMS side effects, we also stimulated neural processes in two control sites. Using frameless stereotaxy, we positioned the stimulation coil to target (1) the LIPF region that was activated during fMRI (mean xyz = 48 35 5); (2) the homologous righthemisphere region; and (3) an additional left parietal control site. At each site, stimulated items (600 msec of 7-Hz rTMS with Cadwell Round Coil) were intermixed with items presented without concurrent stimulation. Subsequently, subjects performed a recognition memory task for the words encountered. We found support for the predicted causal brain-behavior relationship, which was specific to LIPFC. When comparing recognition scores for stimulated items, normalized for variations in performance on nonstimulated trials, we found that words encoded under LIPFC stimulation were subsequently recognized with higher accuracy than words encoded under stimulation in the two cortical control sites. By contrast, no performance difference emerged when the two control sites were compared with each other. Based on additional analyses of the rTMS effects observed directly at the time of encoding (i.e., on semantic-decision performance), we suggest that LIPFC stimulation may have produced its effect on recognition memory, at least in part, through the triggering of more extensive processing of the stimulated items and an ensuing gain in item distinctiveness. Physiological processes of facilitation probably also contributed to the observed memory benefit. Together, these findings suggest that LIPFC does play a causal role in episodic memory formation.
Sex-Related Difference in Amygdala Activity during Emotionally Influenced Memory Storage

We tested the possibility suggested by previous imaging studies that amygdala participation in the storage of emotionally influenced memory is differentially lateralized in men and women. Male and female subjects received two PET scans for regional cerebral glucose-one while viewing a series of emotionally provocative (negative) films, and a second while viewing a series of matched, but emotionally more neutral, films. Consistent with suggestions from several previously published studies, enhanced activity of the right, but not the left, amygdala in men was related to enhanced memory for the emotional films. Conversely, enhanced activity of the left, but not the right, amygdala in women was related to enhanced memory for the emotional films. These results demonstrate a clear gender-related lateralization of amygdala involvement in emotionally influenced memory, and indicate that theories of the neurobiology of emotionally influenced memory must begin to account for the influence of gender.
Engendering allograft ignorance in a mouse model of allogeneic skin transplantation to the distal hind limb.

OBJECTIVE The aim of this study was to demonstrate lymphatic isolation in a model of hind limb lymph node (LN) excision, consisting of ipsilateral popliteal and inguinal LN excision and to evaluate the immunologic response to allogeneic skin transplanted onto this region of lymphatic isolation. METHODS To study lymphatic flow, C57BL/6 mice underwent lymphadenectomy (n = 5), sham lymphadenectomy (n = 5), or no intervention (n = 5), followed by methylene blue injection. Mice were dissected to determine whether methylene blue traveled to the iliac LN. To study host response to skin transplantation, C57BL/6 mice underwent allogeneic skin transplantation with LN excision (n = 6), allogeneic skin transplantation alone (n = 6), or syngeneic skin transplantation (n = 4). Skin grafts were placed distal to the popliteal fossa and mice were euthanized at day 10. Grafts were stained for endothelial cell and proliferation markers (CD31 and Ki67, respectively). Secondary lymphoid tissues (spleen, ipsilateral axillary LN, and contralateral inguinal LN) were removed and rechallenged with BALB/c alloantigen in vitro with subsequent assay of interferon-γ and interleukin 4 cell expression using ELISPOT technique. RESULTS Mice that underwent LN excision had no evidence of methylene blue in the iliac nodes; mice without surgical intervention or with sham LN excision consistently had methylene blue visible in the ipsilateral iliac nodes. Mice treated with allogeneic skin transplantation and LN excision had lower expression of interferon-γ and interleukin 4 in the secondary lymphoid tissues. CONCLUSIONS Lymph node excision completely interrupts lymphatic flow of the hind limb. This model of lymphatic isolation impairs the ability of the transplant recipient to acutely mount a Th1 or Th2 response to allogeneic skin transplants.
Chromosomal abnormalities and reproductive outcome in Malaysian couples with miscarriages.

INTRODUCTION This study was done to determine the prevalence of chromosomal abnormalities and the subsequent reproductive outcome in couples who had two or more miscarriages. METHODS 56 couples with a history of at least two previous miscarriages were evaluated for prevalence and types of chromosomal abnormalities from their karyotype records. The study was a retrospective one, and subsequent reproductive outcome after a period of 12-24 months from the time of karyotyping was obtained by telephone interviews and scrutiny of the case records. The comparison of reproductive outcome was done by chi-square statistics. RESULTS Five couples (8.9 percent) had a chromosomal abnormality in one partner. Three cases of reciprocal translocations t(5;11), t(9;14), dup(9q); one Robertsonian D/D translocation 13/14; and one mosaic Down syndrome male karyotype were found. Among the 32 couples available for follow-up, there was a lower incidence of subsequent live healthy births among chromosomally-normal couples (35.7 percent) compared to chromosomally-abnormal ones (25 percent). However, the difference was not statistically significant (p-value is 1.0). There was a lower incidence of subsequent abortions in chromosomally-normal couples (42.8 percent) compared to chromosomally-abnormal ones (50 percent), but the difference was also not statistically significant (p-value is 1.0). CONCLUSION Chromosomal abnormalities were seen in 8.9 percent of the couples, and translocations were the commonest abnormality found. The frequencies of subsequent live healthy births and subsequent abortions showed no significant difference between couples having normal karyotypes and those having chromosomal abnormality in one partner.
Negative Pressure-Temperature Slopes for Reactions Formign MgSiO3 Perovskite from Calorimetry

A new and sensitive differential drop solution calorimetric technique was developed for very small samples. A single experiment using one 5.18-milligram sample of perovskite, synthesized at 25 gigapascals and 1873 Kelvin, gave 110.1 � 4.1 kilojoules per mole for the enthalpy of the ilmenite-pervoskite transition in MgSiO3. The thermodynamics of the reaction of MgSiO3 (ilmenite) to MgSiO3 (perovskite) and of Mg2SiO4 (spinel) to MgSiO3 (pervoskite) and MgO (periclase) were assessed. Despite uncertainties in heat capacity and molar volume at high pressure and temperature, both reactions clearly have negative pressure-temperature slopes, -0.005 � 0.002 and -0.004 � 0.002 gigapascals per Kelvin, respectively. The latter may be insufficiently negative to preclude whole-mantle convection.
Influence of humidity and voltage on characteristic decomposition components under needle-plate discharge model

Detecting the decomposition components in air-insulated switchgear is an effective method to evaluate the discharge severity of air-insulated switchgear. Experimental and theoretical studies are conducted to investigate the types of decomposition components and generation mechanism under the partial and disruptive discharge conditions. The discharge experiments use a needle-plate discharge tank, and the effect of relative humidity (50, 70 and 90%) and voltage (6, 6.5, 7 and 7.5 kV) are studied in detail. Considering the partial discharge process, the concentrations of CO and NO2 increase with the applied voltage and partial discharge time. The CO concentration increases with the increase of humidity, while NO2 concentration shows the reverse change trend. During the disruptive discharge process, the decomposition component NO increases with humidity. The dissipation of these decomposition components is also investigated using experiment. The small part of CO dissipation is from the adsorption with H2O molecules and onto the surface of discharge tank. The reaction between NO and O free radical, O2 and O3 consumes the concentration of NO and produces NO2. And the reaction between NO2 and H2O consumes most of the generated NO2 in the discharge tank. In the theoretical research, the reaction energy of CO, NO and NO2 generation is computed to analyze the generation and dissipation mechanism of decomposition components using Materials Studio.
Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography.

OBJECTIVE The purpose of this study was to evaluate contrast-enhanced Doppler sonography with perfusion software as a predictor of early tumor response to imatinib (Glivec) in c-kit-positive gastrointestinal stromal tumors (GISTs). SUBJECTS AND METHODS Thirty patients (59 tumors) with metastases or a recurrence from a GIST were prospectively included in a single-center imaging trial. Contrast-enhanced Doppler sonography was performed with an Aplio scanner the day before (day-1) starting oral treatment (400 mg) and at days 1, 7, 14, 60, 90, and 6 months, 9 months, and 1 year. The percentage of contrast uptake (Levovist or Sonovue) before treatment and at the different stages of follow-up was evaluated by two radiologists. Digitized quantification was performed using Photoshop software. To define the benchmark standard, all patients were rated as responders or nonresponders at 2 and 6 months by a board consisting of oncologists and radiologists who had all clinical and imaging data at their disposal. Changes in the percentage of contrast uptake at each sonographic examination were compared statistically. RESULTS A total of 185 examinations were performed. Forty-four lesions in 24 patients were completely evaluated at 2 months, and 29 lesions in 15 patients were completely evaluated at 6 months. Initial contrast uptake at day 1 was predictive of the future response. A strong correlation was found between the decline in tumor contrast uptake at days 7 and 14 and tumor response (p < 10(-4)). CONCLUSION Contrast-enhanced Doppler sonography is a noninvasive imaging technique that allows the early prediction of tumor response in c-kit-positive GIST treated with Glivec.
Chlamydia pneumoniae may be associated with lung cancer:

Material from 117 consecutive patients with lung cancer was investigated with respect to serological markers for chronic Chlamydia pneumoniae infection. Specific C. pneumoniae IgA antibodies were found significantly more often in patients with lung cancer than in control groups with coronary heart disease and in healthy controls, even after adjustment for smoking. The results suggest that chronic C. pnmmoniae infection is common in patients with lung cancer.
Acute blood–brain barrier opening in experimentally induced focal cerebral ischemia is preferentially identified by quantitative magnetization transfer imaging

Pathologic changes in brain tissue during and after stroke may lead to injury of the blood–brain barrier (BBB) and subsequent hemorrhagic transformation (HT). In a rat model of HT, the apparent diffusion coefficient of water, cerebral blood flow, relaxation times, T1 and T2, and magnetization transfer (MT) related parameters (T1sat, Kfor and the MT ratio) were repetitively measured during 3 h of focal ischemia and 2 h of reperfusion (n = 8). Areas of BBB opening were identified by sequential assay of the transcapillary influx of Gd‐diethylenetriaminepentaacetic acid (Gd‐DTPA) by MRI and 14C‐α‐aminoisobutyric acid (AIB) by quantitative autoradiography. Ischemia‐injured regions of interest were identified from the MRI data and divided into those with and without BBB opening. Of the several MRI parameters measured, the T1sat in the caudate‐putamen and preoptic area during ischemia and the first 2 h of reperfusion correlated best with the regional pattern of BBB opening observed thereafter. These data suggest that an ipsilateral/contralateral T1sat ratio > 1.6 demarcates leakage of small molecules such as Gd‐DTPA and AIB across the BBB. As to clinical relevance, the quantitation of MT parameters in acute stroke may enable the early detection of areas of BBB opening and potential HT. Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.
The Serine Protease Autotransporters TagB, TagC, and Sha from Extraintestinal Pathogenic Escherichia coli Are Internalized by Human Bladder Epithelial Cells and Cause Actin Cytoskeletal Disruption

TagB, TagC (tandem autotransporter genes B and C), and Sha (Serine-protease hemagglutinin autotransporter) are recently described members of the SPATE (serine protease autotransporters of Enterobacteriaceae) family. These SPATEs can cause cytopathic effects on bladder cells and contribute to urinary tract infection in a mouse model. Bladder epithelial cells form an important barrier in the urinary tract. Some SPATEs produced by pathogenic E. coli are known to breach the bladder epithelium. The capacity of these newly described SPATEs to alter bladder epithelial cells and the role of the serine protease active site were investigated. All three SPATE proteins were internalized by bladder epithelial cells and altered the distribution of actin cytoskeleton. Sha and TagC were also shown to degrade mucin and gelatin respectively. Inactivation of the serine catalytic site in each of these SPATEs did not affect secretion of the SPATEs from bacterial cells, but abrogated entry into epithelial cells, cytotoxicity, and proteolytic activity. Thus, our results show that the serine catalytic triad of these proteins is required for internalization in host cells, actin disruption, and degradation of host substrates such as mucin and gelatin.
Duodenal cytotoxic lymphocytes in cow's milk protein sensitive enteropathy and coeliac disease

Objective. Pathogenetic mechanisms of cow's milk protein-sensitive enteropathy (CMSE) are poorly defined, but elevated serum granzyme levels and an increase in duodenal intraepithelial lymphocytes (IELs) expressing TIA-1 suggest the involvement of abnormal lymphocyte cytotoxicity. To evaluate cytotoxicity in CMSE we analysed the expression of cytotoxic granule components in duodenal IELs. For comparison, we studied subjects with coeliac disease (CD), in which lymphocyte cytotoxicity is pathogenically important. Material and methods. Fifty-four children were examined by endoscopy for gastrointestinal complaints. Twenty-one subjects had a final diagnosis of CMSE, 15 children had untreated CD and 18 controls showed no definite gastrointestinal disease. Mucosal samples furnished from the bulb and descending duodenum were stained for CD3, perforin, granzymes A and B and TIA-1. Results. In both CMSE and CD, increase of mid-duodenal TIA-1, perforin and granzyme A expressing IELs was seen, the counts in CD being much higher, and increased expression was also seen in the bulb. Granzyme B expression was increased only in CD. In CMSE, no evidence of villous atrophy was seen. Conclusions. Increase in duodenal IELs expressing cytotoxic granules is a characteristic feature in CMSE, although to a lesser degree than in CD. Cytotoxicity is suggested to be involved in the pathogenesis of intestinal dysfunction in CMSE, but based on the absence of villous abnormalities may not be mainly targeted to enterocytes. The mechanisms leading to the accumulation of these cells in CMSE need further investigation.
Technetium-99m-HMPAO, technetium-99m-ECD and iodine-123-IMP cerebral blood flow measurements with pharmacological interventions in primates.

UNLABELLED Technetium-99m-bicisate ethyl cysteinate dimer (ECD) presents a different pattern from cerebral blood flow (CBF) in the subacute phase of cerebral infarction, as measured by PET, perhaps due to lack of oxygen and enzyme activity; this pattern is contrary to that of hexamethyl-propyleneamine oxime (HMPAO) but similar to that of N-isopropyl-[123I]beta-iodoamphetamine ([123I]IMP). This study explores possible CBF differences among HMPAO, ECD and IMP, with various relevant drug interventions. METHODS Anesthetized adult baboons were used in these SPECT studies. Four studies (n = 6 baboons for each study), one control study and three intervention studies involving intravenous acetazolamide, nimodipine infusion and intramuscular sumatriptan, were followed with 99mTc-HMPAO, 99mTc-ECD and [123I]IMP. The split-dose method was used as follows. For each tracer, intervention data from the second SPECT (SPECT-2) after the second tracer injection (444 MBq) reflected a change in CBF with respect to the baseline SPECT (SPECT-1) data from the initial injection (222 MBq). These changes as a ratio, R (R = SPECT-2/SPECT-1), for each study, and the R values for each tracer were compared to R values from the corresponding control studies, yielding a quantitative estimate of drug effects. RESULTS There were no significant differences (p > 0.05) between HMPAO and ECD for the control, acetazolamide and sumatriptan studies, but there was indeed a difference between the two for the nimodipine study, indicating a nimodipine-dependent underestimation of CBF with ECD (and also with IMP), with respect to HMPAO. A further significant difference was that larger CBF increases were observed with acetazolamide, as measured with [123I]IMP. CONCLUSION This is a crucial observation for the clinical interpretation of CBF SPECT data and should direct the choice of tracer for a specific examination.
Control of Severe Hemorrhage Using C-Clamp and Pelvic Packing in Multiply Injured Patients With Pelvic Ring Disruption

Objectives Evaluation of diagnostic and therapeutic workup in multiply injured patients with pelvic ring disruption and hemorrhagic shock. Design Prospective study. Patients Twenty consecutive multiply injured patients (ISS: 41.2 ± 15.3 points) with pelvic ring disruption and hemorrhagic shock. Intervention A C-clamp was used for primary stabilization of the pelvic ring instability. In patients with persistent or massive hemorrhage, laparotomy and pelvic packing were performed. Consecutive measurements of blood lactate levels during the early period after injury. Main Outcome Measurements Lactate, mortality. Results A C-clamp was applied in all patients within 57.4 ± 30.6 minutes of arrival. Fourteen patients underwent laparotomy with pelvic packing for control of hemorrhage, three patients additional resuscitation thoracotomy (aortic clamping:n = 2). Four patients died of exsanguinating hemorrhage during the first 5.4 ± 3.3 hours from arrival, one patient because of septic multi-organ failure twenty-three days after injury (total mortality: 5/20; 25 percent). Lactate levels at admission were elevated in all patients (5.1 ± 2.6 mmol/l). Increased blood lactate levels (4.8 ± 1.7 mmol/l) (+71 percent;p < 0.05) were observed in survivors undergoing laparotomy compared with survivors without laparotomy (2.8 ± 1.1 mmol/l). In contrast, hemoglobin (7.0 ± 2.6 g/dl versus 7.9 ± 2.2 g/dl) and hematocrit (21.4 ± 6.4 percent versus 23.2 ± 6.8 percent) were similar in both groups. In patients who died during the first hours after admission, lactate levels were elevated (8.6 ± 2.5 mmol/l) compared with survivors (4.2 ± 1.8 mmol/l) and increased further. Conclusions Sequential measurements of blood lactate levels during the early period after injury may provide a more rapid and reliable estimation of true severity of hemorrhage than routinely used parameters. Pelvic packing in addition to pelvic ring fixation with a C-clamp allows for effective control of severe hemorrhage in multiply injured patients with pelvic ring disruption.
Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B

Mutations or deletions involving ZFHX1B (previously SIP1) have recently been found to cause one form of syndromic Hirschsprung disease (HSCR), associated with microcephaly, mental retardation, and distinctive facial features. Patients with the characteristic facial phenotype and severe mental retardation, but without HSCR, have now also been shown to have mutations in this gene. Mutations of ZFHX1B are frequently associated with other congenital anomalies, including congenital heart disease, hypospadias, renal tract anomalies, and agenesis of the corpus callosum (ACC). We present the clinical data and mutation analysis results from a series of 23 patients with this clinical syndrome, of whom 21 have proven ZFHX1B mutations or deletions (15 previously unpublished). Two patients with the typical features (one with and one without HSCR) did not have detectable abnormalities of ZFHX1B. We emphasize that this syndrome can be recognized by the facial phenotype in the absence of either HSCR or other congenital anomalies, and needs to be considered in the differential diagnosis of dysmorphism with severe mental retardation +/− epilepsy. © 2003 Wiley‐Liss, Inc.