Miracle-dz/UniFAR-FTUs huggingface dataset:
The combined effect of Pdx1 overexpression and Shh manipulation on the function of insulin‐producing cells derived from adipose‐tissue stem cells

Pancreatic and duodenal homeobox 1 (Pdx1) and Sonic hedgehog (Shh) are the key regulators of beta‐cell function. In vitro experiments have shown that there is significant cooperation between Pdx1 and Shh with regard to the production and maintenance of insulin‐producing cells (IPCs). In this study, the combined effect of Pdx1 overexpression and Shh manipulation on the function of adipose tissue‐derived IPCs was determined. A eukaryotic expression vector (Pdx1‐pCDNA3.1(+)) was constructed and transfected into a Chinese hamster ovary (CHO) cell line. Adipose tissue‐derived mesenchymal stem cells (ADMSCs) obtained from rats were assigned to two groups [control (C) and manipulated (M)] and differentiated into IPCs. Manipulated cells were treated with a mixture of FGF‐β and cyclopamine and recombinant Shh protein at days 3 and 11, respectively, and transfected with Pdx1‐pCDNA3.1(+) at day 10. The expression of multiple genes related to function of beta cells was analyzed using real‐time PCR. The functionality of IPCs in vitro was analyzed through dithizone (DTZ) staining and ELISA. IPCs were injected into the tail vein of diabetic rats, and blood glucose and insulin concentrations were measured. CHO cells transfected with Pdx1‐pCDNA3.1(+) showed a significantly higher expression of Pdx1 compared with nontransfected cells. Manipulated IPCs exhibited a significantly higher expression of MafA, Nkx2.2, Nkx6.1, Ngn3, insulin, and Isl1 and a higher insulin secretion in response to glucose challenge in relation to control cells. Rats that received manipulated IPCs exhibited a higher ability to normalize blood glucose and insulin secretion when compared to controls. Our protocol might be used for more efficient cell therapy of patients with diabetes in the future.
Household tuberculosis contact investigation in a tuberculosis-prevalent country

Abstract The high background rates of positive results on the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) sometimes confuse the investigation of tuberculosis (TB) contact in TB-prevalent countries, particularly in elderly contacts. The aim was to investigate the predictive value of TST and IGRA for diagnosing latent TB infection (LTBI) in elderly household contacts in South Korea. In this retrospective study, TST and IGRA results of household contacts of suspected pulmonary TB patients were reviewed according to the index patient's final diagnosis (TB group: culture-confirmed pulmonary TB, non-TB group: pulmonary disease other than TB). A total of 249 contacts were included in the analysis (188 in the TB group and 61 in the non-TB group). In the TB group, TST and IGRA were positive in 42.6% and 45.7% of contacts, respectively. In the non-TB group, TST and IGRA were positive in 32.8% and 23.0% of contacts, respectively. TST did not show any differences between the TB and non-TB groups for any age group, whereas IGRA showed differences between the 2 groups for those ages 18 to 39 and 40 to 59 years. However, there were no significant differences between the groups for the ≥60 years old group. In elderly contacts, neither TST nor IGRA showed clear discrimination of positivity between the groups. Further studies are needed to predict which elderly contacts are at risk for progression to active TB as well as to accurately detect recent Mycobacterium tuberculosis infection in this vulnerable population.
Comorbidities in the diseasome are more apparent than real: What Bayesian filtering reveals about the comorbidities of depression

Comorbidity patterns have become a major source of information to explore shared mechanisms of pathogenesis between disorders. In hypothesis-free exploration of comorbid conditions, disease-disease networks are usually identified by pairwise methods. However, interpretation of the results is hindered by several confounders. In particular a very large number of pairwise associations can arise indirectly through other comorbidity associations and they increase exponentially with the increasing breadth of the investigated diseases. To investigate and filter this effect, we computed and compared pairwise approaches with a systems-based method, which constructs a sparse Bayesian direct multimorbidity map (BDMM) by systematically eliminating disease-mediated comorbidity relations. Additionally, focusing on depression-related parts of the BDMM, we evaluated correspondence with results from logistic regression, text-mining and molecular-level measures for comorbidities such as genetic overlap and the interactome-based association score. We used a subset of the UK Biobank Resource, a cross-sectional dataset including 247 diseases and 117,392 participants who filled out a detailed questionnaire about mental health. The sparse comorbidity map confirmed that depressed patients frequently suffer from both psychiatric and somatic comorbid disorders. Notably, anxiety and obesity show strong and direct relationships with depression. The BDMM identified further directly co-morbid somatic disorders, e.g. irritable bowel syndrome, fibromyalgia, or migraine. Using the subnetwork of depression and metabolic disorders for functional analysis, the interactome-based system-level score showed the best agreement with the sparse disease network. This indicates that these epidemiologically strong disease-disease relations have improved correspondence with expected molecular-level mechanisms. The substantially fewer number of comorbidity relations in the BDMM compared to pairwise methods implies that biologically meaningful comorbid relations may be less frequent than earlier pairwise methods suggested. The computed interactive comprehensive multimorbidity views over the diseasome are available on the web at Co=MorNet: bioinformatics.mit. bme.hu/UKBNetworks.
Physical function of elderly patients with multimorbidity upon acute hospital admission versus 3 weeks post-discharge

Abstract Purpose: To evaluate the change in activities of daily living, grip strength and functional mobility in very old patients >75 years old with multimorbidity upon admission to hospital versus 3 weeks after discharge. A second aim was to explore which baseline variables could predict personal activities of daily living 3 weeks after discharge. Methods: This prospective cohort study included 115 home-dwelling older adults (mean 86 years, standard deviation 5.9). Participants were measured with the Timed Up and Go, grip strength and Barthel Index in hospital (T1) and 3 weeks after discharge (T2). Results: After 3 weeks, the participants had significantly improved their activities of daily living, mobility and muscle strength, but were still physically reduced compared to reference values for age-matched elderly home dwellers and were at high risk of falls and further loss of independence. In the multivariate regression analysis, baseline cognitive function and mobility were independently associated with Barthel Index at T2 and explained 47% of the variance three weeks after discharge. Conclusions: Our findings highlight the importance of applying performance-based assessments for elderly in hospital. The result indicates that frail old adults acutely admitted to hospital are in need of rehabilitation 3 weeks after hospitalization. Implications for Rehabilitation Older people with multimorbidity improve their physical function 3 weeks after hospitalization. Nevertheless, they still are physically reduced with respect to reference values for age-matched elderly home dwellers and far below the cutoff score for their risk of falls, continued health decline and loosing their independence. The results imply that older people with multimorbidity are in need of early rehabilitation program during hospitalization and after hospitalization. The use of performance-based measurements enables us to identify older adults at highest risk of decline in health and function and is a key of identifying frail older peoples need for rehabilitation. The Time up and Go test, Grip Strength test and the Barthel Index are considered to complement each other and regarded as useful assessments for frail older people in hospital with acute illness.
Label‐free detection techniques for protein microarrays: Prospects, merits and challenges

Protein microarrays, on which thousands of discrete proteins are printed, provide a valuable platform for functional analysis of the proteome. They have been widely used for biomarker discovery and to study protein–protein interactions. The accomplishments of DNA microarray technology, which had enabled massive parallel studies of gene expression, sparked great interest for the development of protein microarrays to achieve similar success at the protein level. Protein microarray detection techniques are often classified as being label‐based and label‐free. Most of the microarray applications have employed labelled detection such as fluorescent, chemiluminescent and radioactive labelling. These labelling strategies have synthetic challenges, multiple label issues and may exhibit interference with the binding site. Therefore, development of sensitive, reliable, high‐throughput, label‐free detection techniques are now attracting significant attention. Label‐free detection techniques monitor biomolecular interactions and simplify the bioassays by eliminating the need for secondary reactants. Moreover, they provide quantitative information for the binding kinetics. In this article, we will review several label‐free techniques, which offer promising applications for the protein microarrays, and discuss their prospects, merits and challenges.
Dead zone or oasis in the open ocean? Zooplankton distribution and migration in low-oxygen modewater eddies

The eastern tropical North Atlantic (ETNA) features a mesopelagic oxygen minimum zone (OMZ) at approximately 300–600 m depth. Here, oxygen concentrations rarely fall below 40 µmol O2 kg−1, but are expected to decline under future projections of global warming. The recent discovery of mesoscale eddies that harbour a shallow suboxic (< 5 µmol O2 kg−1) OMZ just below the mixed layer could serve to identify zooplankton groups that may be negatively or positively affected by ongoing ocean deoxygenation. In spring 2014, a detailed survey of a suboxic anticyclonic modewater eddy (ACME) was carried out near the Cape Verde Ocean Observatory (CVOO), combining acoustic and optical profiling methods with stratified multinet hauls and hydrography. The multinet data revealed that the eddy was characterized by an approximately 1.5-fold increase in total area-integrated zooplankton abundance. At nighttime, when a large proportion of acoustic scatterers is ascending into the upper 150 m, a drastic reduction in mean volume backscattering (Sv) at 75 kHz (shipboard acoustic Doppler current profiler, ADCP) within the shallow OMZ of the eddy was evident compared to the nighttime distribution outside the eddy. Acoustic scatterers avoided the depth range between approximately 85 to 120 m, where oxygen concentrations were lower than approximately 20 µmol O2 kg−1, indicating habitat compression to the oxygenated surface layer. This observation is confirmed by time series observations of a moored ADCP (upward looking, 300 kHz) during an ACME transit at the CVOO mooring in 2010. Nevertheless, part of the diurnal vertical migration (DVM) from the surface layer to the mesopelagic continued through the shallow OMZ. Based upon vertically stratified multinet hauls, Underwater Vision Profiler (UVP5) and ADCP data, four strategies followed by zooplankton in response to in response to the eddy OMZ have been identified: (i) shallow OMZ avoidance and compression at the surface (e.g. most calanoid copepods, euphausiids); (ii) migration to the shallow OMZ core during daytime, but paying O2 debt at the surface at nighttime (e.g. siphonophores, Oncaea spp., eucalanoid copepods); (iii) residing in the shallow OMZ day and night (e.g. ostracods, polychaetes); and (iv) DVM through the shallow OMZ from deeper oxygenated depths to the surface and back. For strategy (i), (ii) and (iv), compression of the habitable volume in the surface may increase prey–predator encounter rates, rendering zooplankton and micronekton more vulnerable to predation and potentially making the eddy surface a foraging hotspot for higher trophic levels. With respect to long-term effects of ocean deoxygenation, we expect avoidance of the mesopelagic OMZ to set in if oxygen levels decline below approximately 20 µmol O2 kg−1. This may result in a positive feedback on the OMZ oxygen consumption rates, since zooplankton and micronekton respiration within the OMZ as well as active flux of dissolved and particulate organic matter into the OMZ will decline.
Examining the Reticulocyte Preference of Two Plasmodium berghei Strains during Blood-Stage Malaria Infection

The blood-stage of the Plasmodium parasite is one of the key phases within its life cycle that influences disease progression during a malaria infection. The efficiency of the parasite in infecting red blood cells (RBC) determines parasite load and parasite-induced hemolysis that is responsible for the development of anemia and potentially drives severe disease progression. However, the molecular factors defining the infectivity of Plasmodium parasites have not been completely identified so far. Using the Plasmodium berghei mouse model for malaria, we characterized and compared the blood-stage infection dynamics of PbANKA WT and a mutant parasite strain lacking a novel Plasmodium antigen, PbmaLS_05, that is well conserved in both human and animal Plasmodium parasite strains. Infection of mice with parasites lacking PbmaLS_05 leads to lower parasitemia levels and less severe disease progression in contrast to mice infected with the wildtype PbANKA strain. To specifically determine the effect of deleting PbmaLS_05 on parasite infectivity we developed a mathematical model describing erythropoiesis and malarial infection of RBC. By applying our model to experimental data studying infection dynamics under normal and drug-induced altered erythropoietic conditions, we found that both PbANKA and PbmaLS_05 (-) parasite strains differed in their infectivity potential during the early intra-erythrocytic stage of infection. Parasites lacking PbmaLS_05 showed a decreased ability to infect RBC, and immature reticulocytes in particular that are usually a preferential target of the parasite. These altered infectivity characteristics limit parasite burden and affect disease progression. Our integrative analysis combining mathematical models and experimental data suggests that deletion of PbmaLS_05 affects productive infection of reticulocytes, which makes this antigen a useful target to analyze the actual processes relating RBC preferences to the development of severe disease outcomes in malaria.
Update of ALDH as a Potential Biomarker and Therapeutic Target for AML

Studies employing mouse transplantation have illustrated the role of aldehyde dehydrogenase (ALDH) defining hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs). Besides being a molecular marker, ALDH mediates drug resistance in AML, which induces poor prognosis of the patients. In AML patients, either CD34+ALDHbr population or CD34+CD38−ALDHint population was found to denote LSCs and minimal residual disease (MRD). A bunch of reagents targeting ALDH directly or indirectly have been evaluated. ATRA, disulfiram, and dimethyl ampal thiolester (DIMATE) are all shown to be potential candidates to open new perspective for AML treatment. However, inconsistent results have been shown for markers of LSCs, which makes it even more difficult to differentiate LSCs and HSCs. In this review, we elevated the role of ALDH to be a potential marker to define and distinguish HSCs and LSCs and its importance in prognosis and target therapy in AML patients. In addition to immunophenotypical markers, ALDH is also functionally active in defining and distinguishing HSCs and LSCs and offers intracellular protections against cytotoxic drugs. Targeting ALDH may be a potential strategy to improve AML treatment. Additional studies concerning specific targeting ALDH and mechanisms of its roles in LSCs are warranted.
A case of Mowat?Wilson syndrome with developmental delays and Hirschsprung’s disease

Mowat-Wilson syndrome is an extremely rare genetic disease that is characterized by intellectual disability, facial dysmorphism, Hirschsprung’s disease, and other congenital anomalies. This disorder is caused by heterozygous mutations or deletions in the zinc finger E-box-binding homeobox-2 gene (ZEB2). Thus far, approximately 200 cases of Mowat-Wilson syndrome have been reported worldwide. In Korea, only one case with a 2q22 deletion, which also affects ZEB2, has been previously reported. Here, we describe a patient with Mowat-Wilson syndrome who presented with developmental delays, typical facial dysmorphism, and Hirschsprung’s disease. Molecular analysis of ZEB2 identified a novel heterozygous mutation at c.190dup (p.S64Kfs*6). To our knowledge, this is the second report of a Korean patient with Mowat-Wilson syndrome that has been confirmed genetically.
Sun-Dried Raisins are a Cost-Effective Alternative to Sports Jelly Beans in Prolonged Cycling

Rietschier, HL, Henagan, TM, Earnest, CP, Baker, BL, Cortez, CC, and Stewart, LK. Sun-dried raisins are a cost-effective alternative to sports jelly beans in prolonged cycling. J Strength Cond Res 25(11): 3150–3156, 2011—The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18–33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), ‘flow’ questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L−1 for SDRs and 5.4 ± 0.2 mmol·L−1 for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.
A Novel Color Parameter as a Luminosity Calibrator for Type Ia Supernovae

Type Ia supernovae (SNe Ia) provide us with a unique tool for measuring extragalactic distances and determining cosmological parameters. As a result, the precise and effective calibration for peak luminosities of SNe Ia becomes extremely crucial and thus is critically scrutinized for cosmological explorations. In this Letter, we reveal clear evidence for a tight linear correlation between peak luminosities of SNe Ia and their B - V colors ~12 days after the B maximum denoted by ΔC12. By introducing such a novel color parameter, ΔC12, this empirical correlation allows us to uniformly standardize SNe Ia with decline rates Δm15 in the range of 0.8 < Δm15 < 2.0 and to reduce scatters in estimating their peak luminosities from ~0.5 mag to the levels of 0.18 and 0.12 mag in the V and I bands, respectively. For a sample of SNe Ia with insignificant reddenings of host galaxies [e.g., E(B - V)host ≲ 0.06 mag], the scatter drops further to only 0.07 mag (or 3%-4% in distance), which is comparable to observational accuracies and is better than other calibrations for SNe Ia. This would impact observational and theoretical studies of SNe Ia and cosmological scales and parameters.
Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation

Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer‐associated gene, VHL, was identified through kindred analysis of von Hippel‐Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia‐inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF‐VEGF/PDGF pathway. Recent whole‐exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer‐associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer.
A Real Time Event Detection using Probabilistic Method and Analysing through Twitter

: A probabilistic model provides a way to detect multiple instances of real time events and to estimate the locationof targeted event like earthquakes, typhoons, traffic jams. Forthis, two models have been proposed named temporal and spatialmodels to detect real time events and estimate the targeted eventlocations respectively by dealing with sensor readingappropriately. Our work is based on the twitter-which is used todeal with sensor reading appropriately real time events andparticularly for location estimation. An important characteristic of twitter is its real-time nature. We investigate the real-timeinteraction of events such as earthquakes in twitter and propose an algorithm to monitor tweets and to detect a target event. As an application, we develop an earthquake reporting system for use in Japan. Because of the numerous earthquakes and the large number of Twitter users throughout the country, we can detect an earthquake with high probability (93 percent of earthquakes of Japan Meteorological Agency (JMA) seismic intensity scale 3 or more are detected) merely by monitoring tweets. Our system detects earthquakes promptly and notification is delivered much faster than JMA broadcast announcements.