Miracle-dz/UniFAR-FTUs huggingface dataset:
Session 2: Type 2 Diabetes and MODY

In the past, type 2 diabetes mellitus was considered a disease of adults and older individuals, not a paediatric condition. Over the last decade, however, in the USA and the rest of the world there has been a disturbing trend of increasing cases of type 2 diabetes in children, mirroring increasing rates of obesity. The risk factors for paediatric type 2 diabetes are: (1) obesity and increased body mass index; (2) family history of type 2 diabetes; (3) membership of ethnic minority; (4) puberty (mean age of diagnosis is F13.5 years); (5) female gender; and (6) features of ‘syndrome X’. The common link among these risk factors is insulin resistance, which plays a pivotal role in the pathophysiology of type 2 diabetes. Both insulin resistance and ß-cell failure are present in the fully established diabetes state. Data will be presented on how these risk factors impact on insulin sensitivity and insulin secretion in childhood, ultimately leading to type 2 diabetes. The clinical presentation of type 2 diabetes in children and its distinction from type 1 diabetes will be dis-
INVITED REVIEW SERIES: CUTTING EDGE TECHNOLOGIES

Animal models have been developed to investigate specific components of asthmatic airway inflammation, hyper-responsiveness or remodelling. However, all of these aspects are rarely observed in the same animal. Heaves is a naturally occurring disease of horses that combines these features. It is characterized by stable dust-induced inflammation, bronchospasm and remodelling. The evaluation of horses during well-controlled natural antigen exposure and avoidance in experimental settings allows the study of disease mechanisms in the asymptomatic and symptomatic stages, an approach rarely feasible in humans. Also, the disease can be followed over several years to observe the cumulative effect of repeated episodes of clinical exacerbation or to evaluate long-term treatment, contrasting most murine asthma models. This model has shown complex gene and environment interactions, the involvement of both innate and adaptive responses to inflammation, and the contribution of bronchospasm and tissue remodelling to airway obstruction, all occurring in a natural setting. Similarities with the human asthmatic airways are well described and the model is currently being used to evaluate airway remodelling and its reversibility in ways that are not possible in people for ethical reasons. Tools including antibodies, recombinant proteins or gene arrays, as well as methods for sampling tissues and assessing lung function in the horse are constantly evolving to facilitate the study of this animal model. Research perspectives that can be relevant to asthma include the role of neutrophils in airway inflammation and their response to corticosteroids, systemic response to pulmonary inflammation, and maintaining athletic capacities with early intervention.
Charge-Based Capacitive Sensor Array for CMOS-Based Laboratory-on-Chip Applications

In this paper, we present a capacitive sensor array for highly integrated lab-on-chip (LoC) applications using the charge-based capacitance measurement method (CBCM). The core-CBCM sensor chip is designed and implemented in 0.18 micron CMOS process featuring an array of capacitive sensors; an offset cancellation module and a low complexity analog-to-digital converter (ADC). This sensor chip is incorporated with a microfluidic channel using direct-write fabrication process. We demonstrate the testing results using chemical solvents with known dielectric constants in order to show the viability of the proposed sensor chip for LoCs.
Malnutrition Is Common in Systemic Sclerosis: Results from the Canadian Scleroderma Research Group Database

Objective. Systemic sclerosis (SSc) is a multisystem disease associated with significant morbidity and increased mortality. Little is known about nutritional status in SSc. We investigated the prevalence and demographic and clinical correlates of nutritional status in a large cohort of patients with SSc. Methods. This was a cross-sectional multicenter study of patients (n = 586) from the Canadian Scleroderma Research Group Registry. Patients were assessed with detailed clinical histories, medical examinations, and self-administered questionnaires. The primary outcome was risk for malnutrition using the “malnutrition universal screening tool” (MUST). Multiple logistic regression was used to assess the relationship between selected demographic and clinical variables and MUST categories. Results. Of the 586 patients in the study, MUST scores revealed that almost 18% were at high risk for malnutrition. The significant correlates of high malnutrition risk included the number of gastrointestinal (GI) complaints, disease duration, diffuse disease, physician global assessment of disease severity, hemoglobin, oral aperture, abdominal distension on physical examination, and physician-assessed possible malabsorption. Among 14 GI symptoms, only poor appetite and lack of a history of abdominal swelling and bloating predict MUST. These factors accounted for 24% of the variance in MUST scores. Conclusion. The risk for malnutrition in SSc is moderate and is associated with shorter disease duration, markers of GI involvement, and disease severity. Patients with SSc should be screened for malnutrition, and potential underlying causes assessed and treated when possible.
Human Echo Perception

It has been shown that human test subjects have the ability, under controlled laboratory conditions, to use echoes to detect the presence or absence of targets placed before them. In addition, blind and sighted persons have been able to detect a target monaurally, to make simple shape discriminations, and to locate a target in space. Signal, environmental, and individual variability affect performance in a measurable fashion. This research is an initial step in measuring the limits of a human being's ability to use echoes as a source of information about his physical surroundings. At this point it seems unlikely that the unaided human ear can rival the bat's auditory system for echo perception. It may be, however, that modern technology can partially bridge the evolutionary gap and bring more useful echoes to man's ear than those it now receives. Such an accomplishment would allow us to examine the extent to which man might benefit from this means of sensing his environment.
Biomarkers associated with mortality in patients undergoing dialysis

BACKGROUND Survival for patients commencing renal replacement therapy is around 90% in the first year and 83% at two years after starting dialysis. The factors that appear to predict mortality are comorbidity and frailty associated with kidney disease, glomerular filtration rate, age and biochemical factors. OBJECTIVES To analyse the condition of patients starting renal replacement therapy, based on biomarkers commonly used in clinical practice and their association with mortality, measured 6 and 12 months after initiating replacement therapy. METHODS A one-year prospective follow-up study with 189 patients. Sociodemographic variables, aetiology of renal disease, comorbidities, prior nephrology service monitoring, prior renal transplantation and biochemical parameters at the time of initiating replacement therapy were analysed. RESULTS The overall percentage of death during the one-year follow-up was 6.87%, with 64% of deaths occurring during the first six months. The only variable independently associated with mortality was low albumin levels. CONCLUSION Although most patients in this centre are monitored by a nephrologist prior to starting replacement therapy, many nevertheless fail to achieve the biochemical targets recommended. One such parameter is albumin, which proved at the start of replacement therapy to be an independent predictor of mortality. Findings of this study show the need to intervene on certain biochemical parameters during the pre-dialysis stage and at the start of dialysis, in order to improve survival in this group of patients.
Stressful life events, genetic liability, and onset of an episode of major depression in women.

OBJECTIVE This study was undertaken to clarify how genetic liability and stressful life events interact in the etiology of major depression. METHOD Information about stressful life events and onset of major depressive episodes in the past year was collected in a population-based sample of female-female twin pairs including 2,164 individuals, 53,215 person-months of observation, and 492 onsets of depression. RESULTS Nine "personal" and three aggregate "network" stressful events significantly predicted onset of major depression in the month of occurrence, four of which predicted onset with an odds ratio of > 10 and were termed "severe": death of a close relative, assault, serious marital problems, and divorce/breakup. Genetic liability also had a significant impact on risk of onset of depression. For severe stressful events, as well as for 10 of the 12 individual stressful events, the best-fitting model for the joint effect of stressful events and genetic liability on onset of major depression suggested genetic control of sensitivity to the depression-inducing effects of stressful life events. In individuals at lowest genetic risk (monozygotic twin, co-twin unaffected), the probability of onset of major depression per month was predicted to be 0.5% and 6.2%, respectively, for those unexposed and exposed to a severe event. In those at highest genetic risk (monozygotic twin, co-twin affected), these probabilities were 1.1% and 14.6%, respectively. Linear regression analysis indicated significant Genotype by Environment interaction in the prediction of onset of major depression. CONCLUSIONS Genetic factors influence the risk of onset of major depression in part by altering the sensitivity of individuals to the depression-inducing effect of stressful life events.
Aspartame and Seizure Susceptibility: Results of a Clinical Study in Reportedly Sensitive Individuals

Summary: The high intensity sweetener aspartame has been implicated anecdotally in seizure provocation. This possibility was investigated with a randomized, double‐blind, placebo‐controlled, cross‐over study. After an extensive search, 18 individuals (16 adults and 2 children) who had seizures allegedly related to aspartame consumption were admitted to adult or pediatric epilepsy monitoring units where their EEG was monitored continuously for 5 days. Aspartame (50 mg/kg) or identically enpackaged placebo was administered in divided doses at 800, 1000, and 1200 h on study days 2 and 4. All meals were uniformly standardized on treatment days. No clin‐ical seizures or other adverse experiences were observed after aspartame ingestion. Mean plasma phenylalanine (Phe) concentrations increased significantly after aspar‐tame ingestion (83.6 pIM) as compared with placebo (52.3 μCM). Results suggest that aspartame, in acute dosage of ε50 mg/kg, is no more likely than placebo to cause seizures in individuals who reported that their seizures were provoked by aspartame consumption.
Bactericidal Activities of Meropenem and Ertapenem against Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in a Neutropenic Mouse Thigh Model

ABSTRACT The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-β-lactamase (ESBL)-producing isolates with a wide range of MICs. Human-simulated dosing regimens in mice were designed to approximate the free drug percent time above the MIC (fT>MIC) observed for humans following meropenem at 1 g every 8 h and ertapenem at 1 g every 24 h. An in vivo neutropenic mouse thigh infection model was used to examine the bactericidal effects against 31 clinical ESBL Escherichia coli and Klebsiella pneumoniae isolates and 2 non-ESBL isolates included for comparison at a standard 105 inoculum. Three isolates were examined at a high 107 inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (μg/ml) of 0.125 (0.03 to 32), than did ertapenem, with 0.5 (0.012 to 128). Seven of the 31 ESBL isolates were removed from the efficacy analysis due to their inability to establish infection in the mouse model. When MICs were ≤1.5 μg/ml for ertapenem (≤0.5 μg/ml for meropenem), similar reductions in CFU (≈ 2-log kill) were observed for both ertapenem (fT>MIC ≥ 23%) and meropenem (fT>MIC ≥ 75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of ≥2 μg/ml (fT>MIC ≤ 20%), while meropenem displayed antibacterial potency that varied from a static effect to a 1-log bacterial reduction in these isolates (fT>MIC = 30 to 65%). At a 107 inoculum, both agents eradicated bacteria due to adequate exposures (fT>MIC = 20 to 45%). Due to low MICs, no difference in bacterial kill was noted for the majority of ESBL isolates tested. However, for isolates with raised ertapenem MICs of ≥2 μg/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC.
Basic Fibroblast Growth Factor (Fgf2) Is Necessary for Cell Proliferation and Neurogenesis in the Developing Cerebral Cortex

Little is known about regionally specific signals that control the number of neuronal progenitor cells in vivo. We have previously shown that the germline mutation of the basic fibroblast growth factor (Fgf2) gene results in a reduction in the number of cortical neurons in the adult. We show here that Fgf2 is expressed in the pseudostratified ventricular epithelium (PVE) in a dorsoventral gradient and that Fgf2 and its receptor, Fgfr-1, are downregulated by mid to late stages of neurogenesis. In Fgf2 knockout mice, the volume and cell number of the dorsal PVE (the cerebral cortical anlage) are substantially smaller, whereas the volume of the basal PVE is unchanged. The dorsal PVE of Fgf2 knockout mice has a 50% decrease in founder cells and a reduced expansion of the progenitor pool over the first portion of neurogenesis. Despite this reduction, the degree of apoptosis within the PVE is not changed in the Fgf2 knockouts. Cortical neuron number was decreased by 45% in Fgf2 knockout mice by the end of neurogenesis, whereas the number of neurons in the basal ganglia was unaffected. Microscopically, the frontal cerebral cortex of neonatal Fgf2 null mutant mice lacked large neurons in deep cortical layers. We suggest that Fgf2 is required for the generation of a specific class of cortical neurons arising from the dorsal PVE.
Surgical Treatment of the Neck in Cancer of the Larynx

Current concepts in management of the clinically negative and clinically positive neck in laryngeal cancer are reviewed. Occult disease in the neck not detected by physical and radiographic examination may also be difficult to identify on routine histologic examination. Immunohistochemistry or molecular analysis may detect metastatic involvement not apparent by light microscopy. The surgeon should be aware of the relatively high incidence of micrometastases in patients with laryngeal cancer to establish optimal treatment approaches. Elective treatment of the neck is recommended for supraglottic tumors staged T2 or higher, and glottic or subglottic tumors staged T3 or higher.The neck may be treated electively by either surgery or irradiation, but irradiation is best reserved for cases where that modality is employed for the primary tumor. Elective neck dissection provides important information for prognostic purposes and therapeutic decisions, by establishing the presence, number, location and nature of occult lymph node metastases. The selective lateral neck dissection (levels II, III and IV), unilateral or bilateral, is the procedure of choice for elective treatment. Paratracheal nodes (level VI) should be dissected in cases of advanced glottic and subglottic cancer. Complete radical or functional neck dissections are excessive in extent, as levels I and V are almost never involved. Sentinel lymph node biopsy may fail to detect tumor on frozen section examination or may not reveal ‘skip’ metastases.The clinically involved neck is usually treated by complete radical or functional neck dissection of levels I through V. Selective neck dissection has been employed successfully in selected cases, particularly for N1 or occasionally N2 nodal involvement. The selective neck dissection can be extended to include structures at risk. More advanced disease has been treated in this manner often in association with adjuvant chemotherapy and/or irradiation. While the benefit of adjuvant treatment is difficult to assess, it appears most useful in cases with extranodal spread of disease, a factor associated with the worst prognosis.
Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by plasmids across genera

Antibiotic resistance is a worldwide public health concern. Conjugative transfer between closely related strains or species of bacteria is an important method for the horizontal transfer of multidrug-resistance genes. The extent to which nanomaterials are able to cause an increase in antibiotic resistance by the regulation of the conjugative transfer of antibiotic-resistance genes in bacteria, especially across genera, is still unknown. Here we show that nanomaterials in water can significantly promote the horizontal conjugative transfer of multidrug-resistance genes mediated by the RP4, RK2, and pCF10 plasmids. Nanoalumina can promote the conjugative transfer of the RP4 plasmid from Escherichia coli to Salmonella spp. by up to 200-fold compared with untreated cells. We also explored the mechanisms behind this phenomenon and demonstrate that nanoalumina is able to induce oxidative stress, damage bacterial cell membranes, enhance the expression of mating pair formation genes and DNA transfer and replication genes, and depress the expression of global regulatory genes that regulate the conjugative transfer of RP4. These findings are important in assessing the risk of nanomaterials to the environment, particularly from water and wastewater treatment systems, and in the estimation of the effect of manufacture and use of nanomaterials on the environment.
Information and housing search: theory and evidence from China market

ABSTRACT Asymmetric market information plays a role in households’ housing choice. To study this role, we theoretically and empirically examine the varied behaviours between better-informed and less-informed households in a housing market. The housing search model theoretically predicts that better-informed households are more likely to secure a better deal. With the data from Tianjin in China, hedonic models are calibrated to quantify the impacts of asymmetric information on housing search outcomes. The results show that the less-informed homebuyers need to pay around 1~2.3% more than those better-informed homebuyers after controlling the heterogeneity of housing units, which are consistent with the theoretical predictions. It suggests that policies and institutions to alleviate asymmetric information in housing market could improve the welfare of households.
Highly Efficient Dual-Switch Hybrid Switching Supply Modulator for Envelope Tracking Power Amplifier

This letter describes a highly efficient dual-switch hybrid switching supply modulator for an envelope tracking power amplifier (PA). The supply modulator has a combined structure of a linear amplifier and a switching amplifier. For an improved efficiency, the switching amplifier employs two buck converters and realizes an adaptive slew rate control of the switching amplifier's current. An implemented envelope tracking PA delivers an efficiency of 39.1% at an output power of 27 dBm for long term evolution signal with 10 MHz channel bandwidth.
Consequences of Increased Compensation Disclosure Transparency: Evidence From CEO Pay in Acquiring Firms

We investigate the consequences of increased compensation disclosure transparency on the pay for chief executive officers (CEOs) in firms that are more prone to a misalignment between manager and shareholder interests. Prior research documents that acquiring CEOs’ pay is insensitive to poor post-deal performance after firms complete large acquisitions. Using the 2006 Securities and Exchange Commission (SEC) compensation disclosure regulation as our empirical setting, we find that this result disappears after firms begin to provide more transparent compensation disclosure. Our cross-sectional analyses show that acquiring firms with higher quality compensation disclosure exhibit greater CEO pay sensitivity to poor post-deal performance after 2006. Our findings indicate that increased compensation disclosure transparency helps strengthen the relation between CEO pay and poor performance in acquiring firms.
Vision-Based Road Bump Detection Using a Front-Mounted Car Camcorder

Advanced vehicle safety is a recently emerging issue, appealed from the rapidly explosive population of car owners. Increasing driver assistance systems have been designed for warning drivers of what should be noticed by analyzing surrounding environments with sensors and/or cameras. As one of the hazard road conditions, road bumps not only damage vehicles but also cause serious danger, especially at night or under poor lighting conditions. In this paper we propose a vision-based road bump detection system using a front-mounted car camcorder, which tends to be widespread deployed. First, the input video is transformed into a time-sliced image, which is a condensed video representation. Consequently, we estimate the vertical motion of the vehicle based on the time-sliced image and infer the existence of road bumps. Once a bump is detected, the location fix obtained from GPS is reported to a central server, so that the other vehicles can receive warnings when approaching the detected bumpy regions. Encouraging experimental results show that the proposed system can detect road bumps efficiently and effectively. It can be expected that traffic security will be significantly promoted through the mutually beneficial mechanism that a driver who is willing to report the bumps he/she meets can receive warnings issued from others as well.
Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells.

In this report we describe the biochemical characterization of neutrophil and monocyte p8 and p14. Together the two proteins comprise approximately 45% of cytosolic protein in neutrophils and approximately 40-fold less in monocytes. They fractionated together in several chromatographic procedures and were found to exist as a noncovalently associated complex with a stoichiometry of 1:1, named p8,14. Cross-linking experiments showed p8,14 to form heterodimers under conditions simulating the cytosol. An apparent molecular mass of 35,000 daltons was obtained for the p8,14 complex in molecular sizing experiments which suggests the presence of modifications or distinctive structural features. Two major forms of p14 can be identified by two-dimensional gel electrophoresis, both of which form heterodimers with p8. The lower molecular weight variant of p14 lacks Cys-3 (Met-Thr-Cys-Lys-Met.) suggesting that differing translational start sites account for these two forms of p14. A protocol has been devised for the rapid purification of milligram quantities of p8 and p14 from neutrophil cytosol using fast-protein liquid chromatography.