Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Biosensor Based on Double-Layer Discharge for the Detection of HPV Type 16

DNA electrochemical biosensors represent a feasible alternative for the diagnosis of different pathologies. In this work, the development of an electrochemical method for Human Papillomavirus-16 (HPV-16) sensing is reported based on potential relaxation measurements related to the discharge of a complex double layer of a DNA-modified gold electrode. The method used allows us to propose an equivalent circuit (EC) for a DNA/Au electrode, which was corroborated by electrochemical impedance spectroscopy (EIS) measurement. This model differs from the Randles circuit that is commonly used in double-layer simulations. The change in the potential relaxation and associated charge transfer resistance were used for sensing the DNA hybridization by using the redox pair Fe(CN)64-/Fe(CN)63+ as an electrochemical indicator. In order to determinate only the potential relaxation of the composed double layer, the faradic and double-layer current contributions were separated using a rectifier diode arrangement. A detection limit of 0.38 nM was obtained for the target HPV-16 DNA sequences. The biosensor showed a qualitative discrimination between a single-base mismatched sequence and the fully complementary HPV-16 DNA target. The results indicate that the discharge of the double-layer detection method can be used to develop an HPV DNA biosensor.
Twenty-Eight Fungal Secondary Metabolites Detected in Pig Feed Samples: Their Occurrence, Relevance and Cytotoxic Effects In Vitro

Feed samples are frequently contaminated by a wide range of chemically diverse natural products, which can be determined using highly sensitive analytical techniques. Next to already well-investigated mycotoxins, unknown or unregulated fungal secondary metabolites have also been found, some of which at significant concentrations. In our study, 1141 pig feed samples were analyzed for more than 800 secondary fungal metabolites using the same LC-MS/MS method and ranked according to their prevalence. Effects on the viability of the 28 most relevant were tested on an intestinal porcine epithelial cell line (IPEC-J2). The most frequently occurring compounds were determined as being cyclo-(L-Pro-L-Tyr), moniliformin, and enniatin B, followed by enniatin B1, aurofusarin, culmorin, and enniatin A1. The main mycotoxins, deoxynivalenol and zearalenone, were found only at ranks 8 and 10. Regarding cytotoxicity, apicidin, gliotoxin, bikaverin, and beauvericin led to lower IC50 values, between 0.52 and 2.43 µM, compared to deoxynivalenol (IC50 = 2.55 µM). Significant cytotoxic effects were also seen for the group of enniatins, which occurred in up to 82.2% of the feed samples. Our study gives an overall insight into the amount of fungal secondary metabolites found in pig feed samples compared to their cytotoxic effects in vitro.
Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service

Emerging from the depths of evolution, pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (i.e., PAC1, VPAC1, VPAC2) are present in multicellular organisms from Tunicates to humans and govern a remarkable number of physiological processes. Consequently, the clinical relevance of PACAP systems spans a multifaceted palette that includes more than 40 disorders. We aimed to present the versatility of PACAP1-38 actions with a focus on three aspects: (1) when PACAP1-38 could be a cause of a malfunction, (2) when PACAP1-38 could be the cure for a malfunction, and (3) when PACAP1-38 could either improve or impair biology. PACAP1-38 is implicated in the pathophysiology of migraine and post-traumatic stress disorder whereas an outstanding protective potential has been established in ischemia and in Alzheimer’s disease. Lastly, PACAP receptors could mediate opposing effects both in cancers and in inflammation. In the light of the above, the duration and concentrations of PACAP agents must be carefully set at any application to avoid unwanted consequences. An enormous amount of data accumulated since its discovery (1989) and the first clinical trials are dated in 2017. Thus in the field of PACAP research: “this is not the end, not even the beginning of the end, but maybe the end of the beginning. ”
The Architecture of Monospecific Microalgae Biofilms

Microalgae biofilms have been proposed as an alternative to suspended cultures in commercial and biotechnological fields. However, little is known about their architecture that may strongly impact biofilm behavior, bioprocess stability, and productivity. In order to unravel the architecture of microalgae biofilms, four species of commercial interest were cultivated in microplates and characterized using a combination of confocal laser scanning microscopy and FTIR spectroscopy. In all the species, the biofilm biovolume and thickness increased over time and reached a plateau after seven days; however, the final biomass reached was very different. The roughness decreased during maturation, reflecting cell division and voids filling. The extracellular polymeric substances content of the matrix remained constant in some species, and increased over time in some others. Vertical profiles showed that young biofilms presented a maximum cell density at 20 μm above the substratum co-localized with matrix components. In mature biofilms, the maximum density of cells moved at a greater distance from the substratum (30–40 μm), whereas the maximum coverage of matrix components remained in a deeper layer. Carbohydrates and lipids were the main macromolecules changing during biofilm maturation. Our results revealed that the architecture of microalgae biofilms is species-specific. However, time similarly affects the structural and biochemical parameters.
Linkage of Periodontitis and Rheumatoid Arthritis: Current Evidence and Potential Biological Interactions

The association between rheumatoid arthritis (RA) and periodontal disease (PD) has been the focus of numerous investigations driven by their common pathological features. RA is an autoimmune disease characterized by chronic inflammation, the production of anti-citrullinated proteins antibodies (ACPA) leading to synovial joint inflammation and destruction. PD is a chronic inflammatory condition associated with a dysbiotic microbial biofilm affecting the supporting tissues around the teeth leading to the destruction of mineralized and non-mineralized connective tissues. Chronic inflammation associated with both RA and PD is similar in the predominant adaptive immune phenotype, in the imbalance between pro- and anti-inflammatory cytokines and in the role of smoking and genetic background as risk factors. Structural damage that occurs in consequence of chronic inflammation is the ultimate cause of loss of function and disability observed with the progression of RA and PD. Interestingly, the periodontal pathogen Porphyromonas gingivalis has been implicated in the generation of ACPA in RA patients, suggesting a direct biological intersection between PD and RA. However, more studies are warranted to confirm this link, elucidate potential mechanisms involved, and ascertain temporal associations between RA and PD. This review is mainly focused on recent clinical and translational research intends to discuss and provide an overview of the relationship between RA and PD, exploring the similarities in the immune-pathological aspects and the possible mechanisms linking the development and progression of both diseases. In addition, the current available treatments targeting both RA and PD were revised.
Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice

Thyroid cancer comprises different clinical and histological entities. Whereas differentiated (DTCs) malignancies are sensitive to radioiodine therapy, anaplastic (ATCs) and medullary (MTCs) tumors do not uptake radioactive iodine and display aggressive features associated with a poor prognosis. Moreover, in a majority of DTCs, disease evolution leads to the progressive loss of iodine sensitivity. Hence, iodine-refractory DTCs, along with ATCs and MTCs, require alternative treatments reflective of their different tumor biology. In the last decade, the molecular mechanisms promoting thyroid cancer development and progression have been extensively studied. This has led to a better understanding of the genomic landscape, displayed by thyroid malignancies, and to the identification of novel therapeutic targets. Indeed, several pharmacological compounds have been developed for iodine-refractory tumors, with four multi-target tyrosine kinase inhibitors already available for DTCs (sorafenib and lenvatinib) and MTCs (cabozantib and vandetanib), and a plethora of drugs currently being evaluated in clinical trials. In this review, we will describe the genomic alterations and biological processes intertwined with thyroid cancer development, also providing a thorough overview of targeted drugs already tested or under investigation for these tumors. Furthermore, given the existing preclinical evidence, we will briefly discuss the potential role of immunotherapy as an additional therapeutic strategy for the treatment of thyroid cancer.
Descriptive analysis of the economic burden of treatment resistance in a major depressive episode

Abstract Objectives: To assess characteristics and healthcare costs associated with pharmacologically treated episodes of treatment-resistant depression (TRD) in patients with major depressive disorder (MDD). Methods: Patients aged ≥18 years with continuous health plan enrollment for ≥12 months before and after a newly observed MDD diagnosis (observed between 1 January 2010 and 31 December 2015) were included in this retrospective claims-based analysis. A pharmacologically treated episode was defined as beginning at the date of the first MDD diagnosis and ending when a gap of 180 days occurred between MDD diagnoses, or when a gap of 180 days occurred following the end of the antidepressant (AD)/antipsychotic (AP) drug supply. When such a gap occurred, the episode end date was determined to be either the date of the last MDD diagnosis or date of the end of AD/AP drug supply, whichever was later. An episode was considered TRD if ≥3 AD regimens occurred. Episode duration, medication regimens used, and relapse hospitalization were reported for TRD and non-TRD MDD episodes. Total all-cause and per-patient-per-month (PPPM) healthcare costs (in 2016 $) were estimated. Results: Of 48,440 patients identified with ≥1 AD-treated MDD episode, the mean (SD) age was 39 (15) years, and 62% were female. Of all episodes, 7% were TRD, with a mean duration of 571 (285) days vs. 200 (198) days for non-TRD MDD episodes. Mean total all-cause costs were $19,626 ($44,160) for TRD and $7440 ($25,150) for non-TRD MDD episodes. Conclusions: Results show TRD episodes are longer and costlier than non-TRD MDD episodes, and that higher costs are driven by episode duration. Longer episodes imply protracted suffering for patients with TRD and increased burden on caregivers. Effective intervention to shorten TRD episodes may lessen disease burden and reduce costs.
Variation in hybrid gene expression: Implications for the evolution of genetic incompatibilities in interbreeding species

Interbreeding species often produce low‐fitness hybrids due to genetic incompatibilities between parental genomes. Whether these incompatibilities reflect fixed allelic differences between hybridizing species, or, alternatively, standing variants that segregate within them, remains unknown for many natural systems. Yet, evaluating these alternatives is important for understanding the origins and nature of species boundaries. We examined these alternatives using spadefoot toads (genus Spea), which naturally hybridize. Specifically, we contrasted patterns of gene expression in hybrids relative to pure‐species types in experimentally produced tadpoles from allopatric parents versus those from sympatric parents. We evaluated the prediction that segregating variation should result in gene expression differences between hybrids derived from sympatric parents versus hybrids derived from allopatric parents, and found that 24% of the transcriptome showed such differences. Our results further suggest that gene expression in hybrids has evolved in sympatry owing to evolutionary pressures associated with ongoing hybridization. Although we did not measure hybrid incompatibilities directly, we discuss the implications of our findings for understanding the nature of hybrid incompatibilities, how they might vary across populations over time, and the resulting effects on the evolutionary maintenance ‐ or breakdown ‐ of reproductive barriers between species.
Hepatitis A and Hepatitis B Vaccination Coverage Among Persons Who Inject Drugs and Have Evidence of Hepatitis C Infection

Objectives: Despite recommendations for vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) for all adults at increased risk of infection, several US states have reported increases in HAV and HBV infections among persons who inject drugs. We investigated hepatitis A and hepatitis B vaccination coverage among a sample of persons who reported injecting drugs and had evidence of hepatitis C virus (HCV) infection. Methods: We searched the Wisconsin Immunization Registry for the vaccination records of persons who underwent HCV testing at syringe services programs from January 1 through August 31, 2018, and were reported to the Wisconsin Division of Public Health as having positive HCV antibody test results and a history of injection drug use. We calculated the percentage of persons who were vaccinated according to national recommendations. Results: Of 215 persons reported, 204 (94.9%) had a client record in the Wisconsin Immunization Registry. Of these 204 persons, 66 (32.4%) had received ≥1 dose of hepatitis A vaccine, 46 (22.5%) had received 2 doses of hepatitis A vaccine, and 115 (56.4%) had received 3 doses of hepatitis B vaccine. Hepatitis B vaccine coverage decreased with increasing age, from 88.0% (22 of 25) among adults aged 20-24 to 30.3% (10 of 33) among adults aged 35-39. Conclusions: These findings suggest that most persons who inject drugs in Wisconsin are susceptible to HAV infection and that most persons aged ≥35 who inject drugs are susceptible to HBV infection. In addition to routine vaccination of children, targeted hepatitis vaccination programs should focus on adults who inject drugs to help prevent future infections.
Perlecan regulates pericyte dynamics in the maintenance and repair of the blood–brain barrier

Pericytes play important roles in the repair of the blood–brain barrier (BBB). Nakamura et al. show that an ECM protein, perlecan, maintains BBB integrity and regulates pericyte recruitment after ischemic stroke through the cooperative function of PDGFRβ and integrin α5β1.
Repeated evolution of terrestrial lineages in a continental lizard radiation

The “early‐burst” model of adaptive radiation predicts an early increase in phenotypic disparity concurrent with lineage diversification. Although most studies report a lack of this coupled pattern, the underlying processes are not identified. The continental radiation of Hemidactylus geckos from Peninsular India includes morphologically diverse species that occupy various microhabitats. This radiation began diversifying ~36 Mya with an early increase in lineage diversification. Here, we test the “early‐burst” hypothesis by investigating the presence of ecomorphs and examining the pattern of morphological diversification in a phylogenetic framework. Two ecomorphs—terrestrial and scansorial species—that vary significantly in body size and toepad size were identified. Unlike the prediction of the “early‐burst” model, we find that disparity in toepad morphology accumulated more recently ~14 Mya and fit the Ornstein‐Ulhenbeck model. Ancestral state reconstruction of the two ecomorphs demonstrates that terrestrial lineages evolved independently at least five times from scansorial ancestors, with the earliest diversification in terrestrial lineages 19–12 Mya. Our study demonstrates a delayed increase in morphological disparity as a result of the evolution of terrestrial ecomorphs. The diversification of terrestrial lineages is concurrent with the establishment of open habitat and grasslands in Peninsular India, suggesting that the appearance of this novel resource led to the adaptive diversification.
The association of intensive care with utilization and costs of outpatient healthcare services and quality of life

Background Little is known about outpatient health services use following critical illness and intensive care. We examined the association of intensive care with outpatient consultations and quality of life in a population-based sample. Methods Cross-sectional analysis of data from 6,686 participants of the Study of Health in Pomerania (SHIP), which consists of two independent population-based cohorts. Statistical modeling was done using Poisson regression, negative binomial and generalized linear models for consultations, and a fractional response model for quality of life (EQ-5D-3L index value), with results expressed as prevalence ratios (PR) or percent change (PC). Entropy balancing was used to adjust for observed confounding. Results ICU treatment in the previous year was reported by 139 of 6,686 (2,1%) participants, and was associated with a higher probability (PR 1.05 [CI:1.03;1.07]), number (PC +58.0% [CI:22.8;103.2]) and costs (PC +64.1% [CI:32.0;103.9]) of annual outpatient consultations, as well as with a higher number of medications (PC +37.8% [CI:17.7;61.5]). Participants with ICU treatment were more likely to visit a specialist (PR 1.13 [CI:1.09; 1.16]), specifically internal medicine (PR 1.67 [CI:1.45;1.92]), surgery (PR 2.42 [CI:1.92;3.05]), psychiatry (PR 2.25 [CI:1.30;3.90]), and orthopedics (PR 1.54 [CI:1.11;2.14]). There was no significant effect regarding general practitioner consultations. ICU treatment was also associated with lower health-related quality of life (EQ-5D index value: PC -13.7% [CI:-27.0;-0.3]). Furthermore, quality of life was inversely associated with outpatient consultations in the previous month, more so for participants with ICU treatment. Conclusions Our findings suggest that ICU treatment is associated with an increased utilization of outpatient specialist services, higher medication intake, and impaired quality of life.
Replicative fitness of seasonal influenza A viruses with decreased susceptibility to baloxavir.

Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold), but also on in vitro replicative fitness. While I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir resistant viruses needed for informed risk assessment.
Fluorescent Radiosensitizing Gold Nanoparticles

Ultrasmall polyaminocarboxylate-coated gold nanoparticles (NPs), Au@DTDTPA and Au@TADOTAGA, that have been recently developed exhibit a promising potential for image-guided radiotherapy. In order to render the radiosensitizing effect of these gold nanoparticles even more efficient, the study of their localization in cells is required to better understand the relation between the radiosensitizing properties of the agents and their localization in cells and in tumors. To achieve this goal, post-functionalization of Au@DTDTPA nanoparticles by near-infrared (NIF) organic dyes (aminated derivative of cyanine 5, Cy5-NH2) was performed. The immobilization of organic Cy5-NH2 dyes onto the gold nanoparticles confers to these radiosensitizers fluorescence properties which can be exploited for monitoring their internalization in cancerous cells, for determining their localization in cells by fluorescence microscopy (a common and powerful imaging tool in biology), and for following up on their accumulation in tumors after intravenous injection.
Integrative Analysis of the Core Fruit Lignification Toolbox in Pear Reveals Targets for Fruit Quality Bioengineering

Stone cell content is an important factor affecting pear fruit flavor. Lignin, a major component of pear stone cells, hinders the quality and value of commercial fruit. The completion of the Chinese white pear (Pyrus bretschneideri) genome sequence provides an opportunity to perform integrative analysis of the genes encoding the eleven protein families (i.e., PAL, C4H, 4CL, HCT, C3H, CSE, CCoAOMT, CCR, F5H, COMT, and CAD) in the phenylpropanoid pathway. Here, a systematic study based on expression patterns and phylogenetic analyses was performed to identify the members of each gene family potentially involved in the lignification in the Chinese white pear. The phylogenetic analysis suggested that 35 P. bretschneideri genes belong to bona fide lignification clade members. Compared to other plants, some multigene families are expanded by tandem gene duplication, such as HCT, C3H, COMT, and CCR. RNA sequencing was used to study the expression patterns of the genes in different tissues, including leaf, petal, bud, sepal, ovary, stem, and fruit. Eighteen genes presented a high expression in fruit, indicating that these genes may be involved in the biosynthesis of lignin in pear fruit. Similarly to what has been observed for Populus trichocarpa, a bimolecular fluorescence complementation (BiFC) experiment indicated that P. bretschneideri C3H and C4H might also interact with each other to regulate monolignol biosynthesis in P. bretschneideri, ultimately affecting the stone cell content in pear fruits. The identification of the major genes involved in lignin biosynthesis in pear fruits provides the basis for the development of strategies to improve fruit quality.
A Fresh Start or the Devil You Know? Examining Relationships Between Release Location Choices, Community Experiences, and Recidivism for High-Risk Parolees

This study investigated the effects of residential relocation in a sample of 282 high-risk male offenders paroled from New Zealand prisons. Initially we compared those returning to their old neighborhoods (devil you know) and those released to a new location (fresh start). This second category was then further divided: those released to a new location voluntarily (fresh start-voluntary) versus those forced to start anew at the behest of the parole board that was releasing them (fresh start-duress). All three categories were then compared on the quality of their community experiences and recidivism. Results indicated that parolees returning by choice to either their old neighborhood or a new location each were reconvicted in the first year after release at approximately the same rate; however, parolees relocating to a new area at the direction of the parole board (under duress) were reconvicted at a higher rate than those in either of the voluntary location categories. Significant group differences in ratings of community life quality were few, but there were some indications that compared with those choosing to return to a familiar location, making a voluntary residential relocation may lead to better parole experiences, particularly in terms of avoiding criminal peers, and that making a residential relocation under duress may lead to poorer parole experiences than for those returning to a familiar location.