Miracle-dz/UniFAR-FTUs huggingface dataset:
Decreased Incidence of Type 1 Diabetes in Young Finnish Children

OBJECTIVE The incidence of type 1 diabetes has been rising for decades, particularly among young children. Between 2006 and 2011, the incidence rate (IR) reached a plateau in Finland. In this observational, register-based cohort study, we assess recent trends in the disease rate in Finnish children. RESEARCH DESIGN AND METHODS Based on data from the Finnish Pediatric Diabetes Register, we studied the incidence of type 1 diabetes among children younger than 15 years of age between 2003 and 2018. We assessed sex-specific IRs per 100,000 person-years (PY) by 4-year time periods in three age-groups (0.50–4.99, 5.00–9.99, and 10.00–14.99 years). RESULTS Among the 7,871 children with newly diagnosed type 1 diabetes, the median age at diagnosis increased from 7.88 to 8.33 years (P = 0.001), while the overall IR decreased from 57.9/100,000 PY in 2003–2006 to 52.2/100,000 PY in 2015–2018, yielding an IR ratio (IRR) of 0.90 (95% CI 0.85–0.96, P = 0.001). This decline was mainly due to the decrease in the youngest age-group (IRR 0.77 [95% CI 0.68–0.87]; P < 0.001), being significant both among boys and girls. In the middle age-group, a significant decrease was observed only among girls. No changes were observed in the oldest children. CONCLUSIONS The incidence of type 1 diabetes decreased among young Finnish children between 2003 and 2018. Current findings imply that environmental factors driving the immune system toward islet autoimmunity are changing in young children.
Heterochiasmy and Sexual Dimorphism: The Case of the Barn Swallow (Hirundo rustica, Hirundinidae, Aves)

Heterochiasmy, a sex-based difference in recombination rate, has been detected in many species of animals and plants. Several hypotheses about evolutionary causes of heterochiasmy were proposed. However, there is a shortage of empirical data. In this paper, we compared recombination related traits in females and males of the barn swallow Hirundo rustica (Linnaeus, 1758), the species under strong sexual selection, with those in the pale martin Riparia diluta (Sharpe and Wyatt, 1893), a related and ecologically similar species with the same karyotype (2N = 78), but without obvious sexual dimorphism. Recombination traits were examined in pachytene chromosome spreads prepared from spermatocytes and oocytes. Synaptonemal complexes and mature recombination nodules were visualized with antibodies to SYCP3 and MLH1 proteins, correspondingly. Recombination rate was significantly higher (p = 0.0001) in barn swallow females (55.6 ± 6.3 recombination nodules per autosomal genome), caused by the higher number of nodules at the macrochromosomes, than in males (49.0 ± 4.5). They also showed more even distribution of recombination nodules along the macrochromosomes. At the same time, in the pale martin, sexual differences in recombination rate and distributions were rather small. We speculate that an elevated recombination rate in the female barn swallows might have evolved as a compensatory reaction to runaway sexual selection in males.
Update on MRI of Cystic Renal Masses Including Bosniak Version 2019

Incidental cystic renal masses are common, usually benign, and almost always indolent. Since 1986, the Bosniak classification has been used to express the risk of malignancy in a cystic renal mass detected at imaging. Historically, magnetic resonance imaging (MRI) was not included in that classification. The proposed Bosniak v.2019 update has formally incorporated MRI, included definitions of imaging terms designed to improve interobserver agreement and specificity for malignancy, and incorporated a variety of masses that were incompletely defined or not included in the original classification. For example, at unenhanced MRI, homogeneous masses markedly hyperintense at T2‐weighted imaging (similar to cerebrospinal fluid) and homogeneous masses markedly hyperintense at fat suppressed T1‐weighted imaging (approximately ≥2.5 times more intense than adjacent renal parenchyma) are classified as Bosniak II and may be safely ignored, even when they have not been imaged with a complete renal mass MRI protocol. MRI has specific advantages and is recommended to evaluate masses that at computed tomography (CT) 1) have abundant thick or nodular calcifications; 2) are homogeneous, hyperattenuating, ≥3 cm, and nonenhancing; or 3) are heterogeneous and nonenhancing. Although MRI is generally excellent for characterizing cystic renal masses, there are unique weaknesses of MRI that bear consideration. These details and others related to MRI of cystic renal masses are described in this review, with an emphasis on Bosniak v.2019. A website (https://bosniak-calculator.herokuapp.com/) and mobile phone apps named “Bosniak Calculator” have been developed for ease of assignment of Bosniak classes.
Proteomic analysis of low‐ to high‐grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin

Proteomic approaches have been useful for the identification of aberrantly expressed proteins in complex diseases such as cancer. These proteins are not only potential disease biomarkers, but also targets for therapy. The aim of this study was to identify differentially expressed proteins in diffuse astrocytoma grade II, anaplastic astrocytoma grade III and glioblastoma multiforme grade IV in human tumor samples and in non-neoplastic brain tissue as control using 2-DE and MS. Tumor and control brain tissue dissection was guided by histological hematoxylin/eosin tissue sections to provide more than 90% of tumor cells and astrocytes. Six proteins were detected as up-regulated in higher grade astrocytomas and the most important finding was nucleophosmin (NPM) (po0.05), whereas four proteins were down-regulated, among them raf kinase inhibitor protein (RKIP) (po0.05). We report here for the first time the alteration of NPM and RKIP expression in brain cancer. Our focus on these proteins was due to the fact that they are involved in the PI3K/AKT/ mTOR and RAS/RAF/MAPK pathways, known for their contribution to the development and progression of gliomas. The proteomic data for NPM and RKIP were confirmed by Western blot, quantitative real-time PCR and immunohistochemistry. Due to the participation of NPM and RKIP in uncontrolled proliferation and evasion of apoptosis, these proteins are likely targets for drug development.
An Interdisciplinary Mixed-Methods Approach to Analyzing Urban Spaces: The Case of Urban Walkability and Bikeability

Human-centered approaches are of particular importance when analyzing urban spaces in technology-driven fields, because understanding how people perceive and react to their environments depends on several dynamic and static factors, such as traffic volume, noise, safety, urban configuration, and greenness. Analyzing and interpreting emotions against the background of environmental information can provide insights into the spatial and temporal properties of urban spaces and their influence on citizens, such as urban walkability and bikeability. In this study, we present a comprehensive mixed-methods approach to geospatial analysis that utilizes wearable sensor technology for emotion detection and combines information from sources that correct or complement each other. This includes objective data from wearable physiological sensors combined with an eDiary app, first-person perspective videos from a chest-mounted camera, and georeferenced interviews, and post-hoc surveys. Across two studies, we identified and geolocated pedestrians’ and cyclists’ moments of stress and relaxation in the city centers of Salzburg and Cologne. Despite open methodological questions, we conclude that mapping wearable sensor data, complemented with other sources of information—all of which are indispensable for evidence-based urban planning—offering tremendous potential for gaining useful insights into urban spaces and their impact on citizens.
Comparison of Isolation, Expansion and Cryopreservation Techniques to Produce Stem Cells from Human Exfoliated Deciduous teeth (SHED) with better Regenerative Potential.

Mesenchymal stem cells (MSCs) are adult stem cells that are gaining worldwide attention for its multi-potential use in tissue engineering-based regenerative medicine. They can be obtained from numerous sources and one of the excellent source is from the dental tissue, such as stem cells that are extracted from the human exfoliated deciduous teeth (SHEDs). SHEDs are considered ideal due to its inherent characteristics, including the capability to proliferate quickly with minimal oncogenesis risk, multipotency capacity and its ability to suppress the immune system. On top of these positive cell traits, SHEDs are easily accessible with patient's safety assured, posing less ethical issues and could also provide sufficient cells number for prospective clinical uses. This is primarily attributed to its ability to differentiate into multiple cell linages, including osteoblasts, odontoblasts, neuronal cells, adipocytes, as well as endothelial cells. Albeit SHEDs having a bright future, there still remains an obstacle to develop reliable experimental techniques to retain the long term regeneration potential of the stem cells for prospective research and clinical applications. Therefore, this review aims to describe the various isolation, expansion and cryopreservation techniques used by researchers in this stem cell field. Optimization of these techniques is crucial to obtain distinct SHEDs culture with preserved stem cells properties, which enable more reproducible results that will be the key for further stem cells therapy development.
The role of calcium in the regulation of Xylella fastidiosa virulence

ii List of Illustrations ii List of Abbreviations ii Chapter 1 Overview of Xylella fastidiosa biology and metals effect on bacterial virulence 1 1. The plant pathogen Xylella fastidiosa 1 1.1 Host Range and Geographic Distribution 1 1.2 Disease Development 2 1.3 Molecular Disease Determinants 4 1.4 Role of Nutrients in Bacterial Biology 5 2 The influence of Ca on bacterial virulence 7 2.1 Calcium has structural and regulatory functions 7 2.2 Acquisition and distribution by plants 8 2.3 Roles of calcium in bacterial metabolism 9 2.4 Regulation of calcium homeostasis in bacteria 10 2.5 Role of calcium in bacterial virulence 12 References 21
Rational design of the cold active subtilisin-like serine protease VPR towards higher activity and thermostability

This research project builds on research previously done on the subtilisin-like serine proteinase VPR, from a psychrotrophic Vibrio species and its structural homologue aqualysin I (AQUI) from the thermophile Thermus aquaticus. We set out to design a mutant of VPR using site directed mutagenesis that would be both more stable against heat denaturation and retain the high activity of the wi ld type enzyme. Starting with two different templates, one being a C-terminal truncat ed form of the enzyme (VPR ΔC), containing two proline mutations, N3P/I5P, close to the N-terminus of the protein, which had shown increased stability but loss of catalytic activity. The ∆C truncated form was produced by introducing a mutation as a stop codon at C277 to imitate the structure of AQUI in more detail. The other template contained t he ∆C mutation and additional six mutations on a loop that may act as a hinge for mov e ents that are postulated to be important for catalysis. The A116T/Q117R/A119H/S120 R/G121R/S123A (6x) mutant had shown an increase in activity without losing stabil ity to any degree. On top of these templates two mutations were added; N15D and Q142K. The N15D mutation had been shown to introduce a salt bridge yielding higher st ability but with no detrimental effects on activity. The Q142K exchange on the other hand incr eased significantly the catalytic activity of the enzyme. Thus, we attempted to impro ve stability of the two mutants by introducing the N15D mutation, while the Q142K muta tions was added with the purpose of increasing catalytic activity. The VPR ∆C/N3P/I5P/N15D/Q142K mutant was a success, giving an 8°C rise in the T m, a 10°C rise to the T 50% and the catalytic activity was slightly higher than that of the wild type enzyme. The VPR ∆C/6x/N15D/Q142K led to a 3°C rise in both Tm and T50%. To examine the effects of the N3P/I5P mutation on the flexibility of the structure, fluorescence quenching with acrylamide w as preformed comparing AQUI, VPR∆C and VPR∆C/N3P/I5P. The results indicated that the environmen t of Trp6 in VPR∆C/N3P/I5P is not as accessible as in VPR ∆C probably due to tighter packing of the Nterminus.
Multidrug resistance associated with glutathione

Jedną z głównych przyczyn niepowodzeń w terapii cytostatycznej nowotworów jest występowanie zjawiska oporności wielolekowej (multidrug resistance – MDR), które znacznie ogranicza skuteczność chemioterapii. Niektóre z nowotworów wykazują pierwotną oporność na stosowane cytostatyki, inne natomiast, początkowo wrażliwe, nabywają cechę lekooporności w trakcie stosowanej chemioterapii. Głównymi przyczynami MDR są mechanizmy tłumiące indukcję apoptozy komórki nowotworowej oraz zaburzające akumulację wewnątrzkomórkową leków cytostatycznych i ich metabolizm. Najwcześniej poznanym mechanizmem MDR jest nadekspresja genu mdr-1 i związanej z nim glikoproteiny P (P-gp) pełniącej funkcję pompy błonowej, która może katalizować wypływ wielu strukturalnie niepowiązanych leków z komórek zmienionych nowotworowo. Innym z mechanizmów chroniących oporną na leczenie komórkę nowotworową przed zwiększającym się stężeniem cytostatyków w jej wnętrzu jest zwiększona zdolność do przekształcania leku w formy nietoksyczne. Zwiększona aktywność enzymów detoksykujących, m.in. transferaz glutationowych, peroksydazy glutationowej czy dysmutazy ponadtlenkowej, prowadzi do neutralizacji produktów powstających również w wyniku przemian metabolicznych leków. Ostatnie wyniki badań nad rakiem jajnika dowodzą, że czynnikiem zwiększającym ryzyko wystąpienia tego nowotworu jest obecność i ekspresja polimorfizmów genu kodującego ludzką transferazę S-glutationu. Duże stężenie transferazy S-glutationu jest złym czynnikiem prognostycznym w raku jajnika, a także innych nowotworach, np. raku jelita grubego, niedrobnokomórkowym raku płuc, raku żołądka, przewlekłej białaczce limfatycznej i glejakach. Słowa kluczowe: oporność wielolekowa, nowotwory, glikoproteina P, glutation, rak jajnika.
The Adherence of Singaporean Students in Different Educational Institutions to National Food-Based Dietary Guidelines

There are currently limited data on the dietary habits of young Singaporeans. This study aimed to evaluate the adherence of 17–21 year olds attending different educational institutions using a novel diet-quality scoring method. Dietary data were collected using a single weekday 24 h dietary recall in a cross section of 536 Singaporeans aged 17–21 years. An 11 category scoring system (0.0–100.0) was used to define adherence to food based dietary guidelines. Demographic and self-reported data were also collected via a questionnaire, BMI status, and using Mann-Whitney and Kruskal-Wallis (non-parametric) tests, with post-hoc Bonferroni-corrected tests. The median diet quality score was 48.5 (IQR 40.5, 56.4) for this cohort, with component scores for “Total fruit”, “Whole fruit”, “Total vegetables”, “Dark green leafy & orange vegetables”, “Whole grains”, “Dairy products”, and “Sodium” frequently scoring the minimum value. Median diet quality scores were statistically different for groups by ethnic origin (p < 0.001) and by educational institution (p < 0.001). Intake of fruit, vegetables, and whole grains is minimal, while sodium intake is frequently too high in young Singaporeans. Differences across ethnic groups and types of educational institutions suggest the need for targeted interventions to improve dietary habits in this population.
Wild Boar as a Sylvatic Reservoir of Hepatitis E Virus in Poland: A Cross-Sectional Population Study

The most important wildlife species in the epidemiology of hepatitis E virus (HEV) infections are wild boars, which are also the main reservoir of the virus in a sylvatic environment. The aim of the study was a serological and molecular assessment of the prevalence of HEV infections in wild boars in Poland. In total, 470 pairs of samples (wild boar blood and livers) and 433 samples of faeces were tested. An ELISA (ID.vet, France) was used for serological analysis. For the detection of HEV RNA, real-time (RT)-qPCR was employed. The presence of specific anti-HEV IgG antibodies was found in 232 (49.4%; 95%CI: 44.7–54%) sera, with regional differences observed in the seroprevalence of infections. HEV RNA was detected in 57 (12.1%, 95%CI: 9.3–15.4%) livers and in 27 (6.2%, 95%CI: 4.1–8.9%) faecal samples, with the viral load ranging from 1.4 to 1.7 × 1011 G.C. /g and 38 to 9.3 × 107 G.C. /mL, respectively. A correlation between serological and molecular results of testing of wild boars infected with HEV was shown. HEV infections in wild boars appeared to be common in Poland.
CCAL1 enhances osteoarthritis through the NF‐κB/AMPK signaling pathway

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and secondary osteogenesis. It has been previously demonstrated that the CCAL1 locus is the gene encoding tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). The purpose of this study was to demonstrate the role of CCAL1 in OA progression and to elucidate its molecular mechanisms. We report that CCAL1 is highly expressed in the cartilage of OA patients and its expression level is positively correlated with the severity of OA. We found that CCAL1 causes a switch to the fibrosis‐prone phenotype of Human Chondrocyte‐Osteoarthritis (HC‐OA) cells. In addition, CCAL1 enhances cell viability and promotes the proliferation of HC‐OA cells. Finally, the detection of proteins associated with the NF‐κB/AMPK signaling pathway by western blot suggested that CCAL1 exerts its role on HC‐OA cells by activating the NF‐κB signaling pathway and inhibiting the AMPK signaling pathway, which was verified through the addition of NF‐κB inhibitor caffeic acid phenethyl ester (CAPE) and AMPK activator 5‐aminoimidazole‐4‐carboxamide riboside (AICAR). In summary, we report that CCAL1 may promote OA through the NF‐κB and AMPK signaling pathways.
The Association between Serum Bilirubin Levels and Colorectal Cancer Risk: Results from the Prospective Cooperative Health Research in the Region of Augsburg (KORA) Study in Germany

Emerging studies have suggested that bilirubin, particularly unconjugated bilirubin (UCB), has substantial anti-inflammatory and antioxidant properties that protect against oxidative stress-associated diseases such as cancer. Few observational studies have investigated the etiological role of bilirubin in colorectal cancer (CRC) development. In this case-control study, nested in the population-based prospective cohort of the Cooperative Health Research in the Region of Augsburg (KORA) study in south Germany, pre-diagnostic circulating UCB concentrations were measured by high-performance liquid chromatography in 77 CRC cases and their individually matched controls. Multivariable unconditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for associations between log-transformed UCB levels (log-UCB), standardized per one-standard-deviation (one-SD) increment, and CRC risk. The models were a priori stratified by sex based on previous evidence. In the fully adjusted models, each one-SD increment in log-UCB was indicative of a positive association with CRC risk (OR, 1.20; 95% CI, 0.52–2.79) among men, and of an inverse association (OR, 0.76; 95% CI, 0.34–1.84) among women (Pheterogeneity = 0.4 for differences between men and women). We found little evidence for sex-specific associations of circulating bilirubin with CRC risk, and further studies are needed to confirm or refute the potential associations.
Review of Decandolle's origin of cultivated plants; with annotations upon certain American species

M. ALPHONSE DE CANDOLLE'S Geograph£e Botanique Raisonnee, in two volumes of nearly 700 pages each, was published in the year 1855, and has been for several years out of print. It is not surprising that the now venerable but still well·busied author should decline the labor of preparing a new edition, involving, as it woula, the re-discussion of certain questions under changed points of view, and the collocation of a vast amount of widely scattered new materials which the last quarter of a century has brought to us. Happily, the chapter on the geographical origin of the species of plants generally cultivated for food, and for other economical uses, could be detached. This, the author has sedulously studied anew; and the present volume is the result. As yet we have it only in the original French j but it is said that an English translation is in preparation. So, if the work is not already in the hands of botanists and other scholars generally, we may expect that it soon will be; and, contenting ourselves with a mere mention of its plan and scope, we may proceed to * Origine des Plantes Gultivees, par ALPH. DE CANDOLLE, Associe Etranger de l'Academie des Sciences de l'Institut de France, etc. Paris, 1883, pp. 377, 8vo. (BibL Scientifique Internationale, XLIII.) Bailliere et Ci,.
Ceftolozane/Tazobactam and Ceftazidime/Avibactam for Multidrug-Resistant Gram-Negative Infections in Immunocompetent Patients: A Single-Center Retrospective Study

Complicated infections from multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a serious problem presenting many challenges. Resistance to many classes of antibiotics reduces the probability of an adequate empirical treatment, with unfavorable consequences, increasing morbidity and mortality. Readily available patient medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. There are few literature data that report real-life experiences in the use of ceftolozane/tazobactam and ceftazidime/avibactam, with particular reference to microbiological cure. Some studies reported experiences for the treatment of MDR-GNB infections in patients with hematological malignancies or specifically in Pseudomonas aeruginosa infections. We report our clinical single-center experience regarding the real-life use of ceftolozane/tazobactam and ceftazidime/avibactam to treat serious and complicated infections due to MDR-GNB and carbapenem-resistant Enterobacterales (CRE), with particular regard given to intra-abdominal and urinary tract infections and sepsis.