Miracle-dz/UniFAR-FTUs huggingface dataset:
Label-Free Biosensors for Laboratory-Based Diagnostics of Infections: Current Achievements and New Trends

Infections pose a serious global public health problem and are a major cause of premature mortality worldwide. One of the most challenging objectives faced by modern medicine is timely and accurate laboratory-based diagnostics of infectious diseases. Being a key factor of timely initiation and success of treatment, it may potentially provide reduction in incidence of a disease, as well as prevent outbreak and spread of dangerous epidemics. The traditional methods of laboratory-based diagnostics of infectious diseases are quite time- and labor-consuming, require expensive equipment and qualified personnel, which restricts their use in case of limited resources. Over the past six decades, diagnostic technologies based on lateral flow immunoassay (LFIA) have been and remain true alternatives to modern laboratory analyzers and have been successfully used to quickly detect molecular ligands in biosubstrates to diagnose many infectious diseases and septic conditions. These devices are considered as simplified formats of modern biosensors. Recent advances in the development of label-free biosensor technologies have made them promising diagnostic tools that combine rapid pathogen indication, simplicity, user-friendliness, operational efficiency, accuracy, and cost effectiveness, with a trend towards creation of portable platforms. These qualities exceed the generally accepted standards of microbiological and immunological diagnostics and open up a broad range of applications of these analytical systems in clinical practice immediately at the site of medical care (point-of-care concept, POC). A great variety of modern nanoarchitectonics of biosensors are based on the use of a broad range of analytical and constructive strategies and identification of various regulatory and functional molecular markers associated with infectious bacterial pathogens. Resolution of the existing biosensing issues will provide rapid development of diagnostic biotechnologies.
Rab11 activation by Ik2 kinase is required for dendrite pruning in Drosophila sensory neurons

Neuronal pruning is a commonly observed phenomenon for the developing nervous systems to ensure precise wiring of neural circuits. The function of Ik2 kinase and its downstream mediator, Spindle-F (Spn-F), are essential for dendrite pruning of Drosophila sensory neurons during development. However, little is known about how Ik2/Spn-F signaling is transduced in neurons and ultimately results in dendrite pruning. Our genetic analyses and rescue experiments demonstrated that the small GTPase Rab11, especially the active GTP-bound form, is required for dendrite pruning. We also found that Rab11 shows genetic interactions with spn-F and ik2 on pruning. Live imaging of single neurons and antibody staining reveal normal Ik2 kinase activation in Rab11 mutant neurons, suggesting that Rab11 could have a functional connection downstream of and/or parallel to the Ik2 kinase signaling. Moreover, we provide biochemical evidence that both the Ik2 kinase activity and the formation of Ik2/Spn-F/Rab11 complexes are central to promote Rab11 activation in cells. Together, our studies reveal that a critical role of Ik2/Spn-F signaling in neuronal pruning is to promote Rab11 activation, which is crucial for dendrite pruning in neurons.
Discrete Hedgehog Factor Expression and Action in the Developing Phallus

Hypospadias is a failure of urethral closure within the penis occurring in 1 in 125 boys at birth and is increasing in frequency. While paracrine hedgehog signalling is implicated in the process of urethral closure, how these factors act on a tissue level to execute closure itself is unknown. This study aimed to understand the role of different hedgehog signalling members in urethral closure. The tammar wallaby (Macropus eugenii) provides a unique system to understand urethral closure as it allows direct treatment of developing offspring because mothers give birth to young before urethral closure begins. Wallaby pouch young were treated with vehicle or oestradiol (known to induce hypospadias in males) and samples subjected to RNAseq for differential expression and gene ontology analyses. Localisation of Sonic Hedgehog (SHH) and Indian Hedgehog (IHH), as well as the transcription factor SOX9, were assessed in normal phallus tissue using immunofluorescence. Normal tissue culture explants were treated with SHH or IHH and analysed for AR, ESR1, PTCH1, GLI2, SOX9, IHH and SHH expression by qPCR. Gene ontology analysis showed enrichment for bone differentiation terms in male samples compared with either female samples or males treated with oestradiol. Expression of SHH and IHH localised to specific tissue areas during development, akin to their compartmentalised expression in developing bone. Treatment of phallus explants with SHH or IHH induced factor-specific expression of genes associated with bone differentiation. This reveals a potential developmental interaction involved in urethral closure that mimics bone differentiation and incorporates discrete hedgehog activity within the developing phallus and phallic urethra.
Syntaxin 1: A Novel Robust Immunophenotypic Marker of Neuroendocrine Tumors

Considering the specific clinical management of neuroendocrine (NE) neoplasms (NENs), immunohistochemistry (IHC) is required to confirm their diagnosis. Nowadays, synaptophysin (SYP), chromogranin A (CHGA), and CD56 are the most frequently used NE immunohistochemical markers; however, their sensitivity and specificity are less than optimal. Syntaxin 1 (STX1) is a member of a membrane-integrated protein family involved in neuromediator release, and its expression has been reported to be restricted to neuronal and NE tissues. In this study, we evaluated STX1 as an immunohistochemical marker of NE differentiation. STX1, SYP, CHGA, and CD56 expression was analyzed in a diverse series of NE tumors (NETs), NE carcinomas (NECs), and non-NE tumors. All but one (64/65; 98%) NETs and all (54/54; 100%) NECs revealed STX1 positivity in at least 50% of the tumor cells. STX1 showed the highest sensitivity both in NETs (99%) and NECs (100%) compared to CHGA (98% and 91%), SYP (96% and 89%), and CD56 (70% and 93%), respectively. A wide variety of non-NE tumors were tested and found to be uniformly negative, yielding a perfect specificity. We established that STX1 is a robust NE marker with an outstanding sensitivity and specificity. Its expression is independent of the site and grade of the NENs.
Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression

Reactive oxygen species (ROS) produced during intracellular metabolism or triggered by extrinsic factors can promote neoplastic transformation and malignant microenvironment that mediate tumor development. Oligo-Fucoidan is a sulfated polysaccharide isolated from the brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages as well as human HCT116 colorectal cancer cells, primary C6P2-L1 colorectal cancer cells and human MDA-MB231 breast cancer cells, we investigated the effect of Oligo-Fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in chemotherapy and tumor prevention. We now demonstrate that Oligo-Fucoidan is an antioxidant that suppresses intracellular ROS and mitochondrial superoxide levels in monocytes/macrophages and in aggressive cancer cells. Comparable to ROS inhibitors (DPI and NAC), Oligo-Fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes. DPI and Oligo-Fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced particularly when DPI suppressed ROS generation and supplemented with Oligo-Fucoidan in the cancer cells. Moreover, cisplatin chemoagent polarized monocytes and M0 macrophages toward M2-like phenotypes and Oligo-Fucoidan supplementation reduced these side effects. Furthermore, Oligo-Fucoidan promoted cytotoxicity of cisplatin and antagonized cisplatin effect on cancer cells to prevent M2 macrophage differentiation. More importantly, Oligo-Fucoidan inhibited tumor progression and M2 macrophage infiltration in tumor microenvironment, thus increasing of anti-tumor immunity.
Ethanol Gas Sensitivity Sensor Based on Roughened POF Taper of Modified Polypyrrole Films

The three polypyrrole (PPy) films with different mixture ratios, namely PPy1, PPy2, and PPy3, were synthesized by chemical oxidation with pyrrole and ferric chloride (FeCl3). The roughened plastic optical fiber (POF) taper assembled PPy films (POF-PPy1, POF-PPy2, and POF-PPy3) were facilely prepared and bent U shape structure for testing ethanol gas at room temperature. The morphologies of the PPy films and the roughened POF taper were studied using electron microscopy. The effect of the three PPy films on the gas response was investigated and the results showed that the POF-PPy2 exhibited a high sensitivity of 5.08 × 10−5 dB/ppm. The detection limit of the sensor was 140 ppm and its response and recovery times were 5 s and 8 s, respectively. The results also showed that as the bending radius decreased, the response and recovery times gradually shortened, while the output power increased. In addition, the proposed sensor has advantages of a low cost and simple structure.
Development of the BioCalculus Assessment (BCA)

We describe the development and initial validity assessment of the 20-item BioCalculus Assessment (BCA), with the objective of comparing undergraduate life science students’ understanding of calculus concepts in different courses with alternative emphases (with and without focus on biological applications). The development process of the BCA included obtaining input from a large network of scientists and educators as well as students in calculus and biocalculus courses to accumulate evidential support of the instrument’s content validity and response processes of test takers. We used the Rasch model to examine the internal structure of scores from students who have experienced calculus instruction in the two methods. The analysis involved three populations (Calculus 1, Calculus 2, and Biocalculus) for which the Calc 1 and Calc 2 students were not exposed to calculus concepts in a life science setting, while the Biocalculus students were presented concepts explicitly with a life science emphasis. Overall, our findings indicate that the BCA has reasonable validity properties, providing a diagnostic tool to assess the relative learning success and calculus comprehension of undergraduate biology majors from alternative methods of instruction that do or do not emphasize life science examples.
Parent and child emotion and distress responses associated with parental accommodation of child anxiety symptoms.

OBJECTIVE Parental accommodation contributes to the maintenance of child anxiety and related symptoms. The current study examines the contributions of parent and child factors to parental accommodation in a sample of anxious youth. METHODS Sixty-four treatment-seeking youth (6-16 years) and their mothers, as well as a subset of fathers (N = 41) reported on parental accommodation, parental distress and emotion regulation, child psychopathology, child externalizing behaviors, and child intolerance of uncertainty. RESULTS Parental accommodation was not related to parental distress or emotion regulation. Parents who viewed their child as being more symptomatic (e.g., anxious, externalizing, and intolerant of uncertainty) were more likely to engage in accommodation. For mothers, child anxiety and externalizing symptoms were notable predictors of accommodation. CONCLUSIONS Parent perceptions of child symptomology is an important factor significantly related to accommodation behaviors. This finding can be used to inform programming designed to target parental responses to child anxiety and related disorders.
Disease burden and seasonal impact of improving rotavirus vaccine coverage in the United States: A modeling study

Background Prior to vaccine introduction in 2006, rotavirus was the leading cause of severe diarrhea in children under five years of age in the U.S. Vaccination of infants has led to major reductions in disease burden, a shift in the seasonal peak and the emergence of a biennial pattern of disease. However, rotavirus vaccine coverage has remained relatively low (70–75%) compared to other infant immunizations in the U.S. Part of the reason for this lower coverage is that children whose care is provided by family practitioners (FP) have considerably lower probability of being vaccinated compared to those seen be pediatricians (PE). We used a dynamic transmission model to assess the impact of improving rotavirus vaccine coverage by FP and/or PE on rotavirus gastroenteritis (RVGE) incidence and seasonal patterns. Methods A deterministic age-structured dynamic model with susceptible, infectious, and recovered compartments (SIRS model) was used to simulate rotavirus transmission and vaccination. We estimated the reduction of RVGE cases by 2 doses of rotavirus vaccine with three vaccination scenarios: (Status Quo: 85% coverage by pediatricians and 45% coverage by family practitioners; Improved FP: 85% coverage by pediatricians and family practitioners; Improved FP+PE: 95% coverage by pediatricians and family practitioners). In addition, we tested the sensitivity of the model to the assumption of random mixing patterns between children visiting pediatricians and children visiting family practitioners. Results In this model, higher vaccine coverage provided by family practitioners and pediatricians leads to lower incidence of severe RVGE cases (23% averted in Improved FP and 57% averted in Improved FP+PE compared to Status Quo) including indirect effects. One critical impact of higher total vaccine coverage is the effect on rotavirus epidemic patterns in the U.S.; the biennial rotavirus epidemic patterns shifted to reduced annual epidemic patterns. Additionally, assortative mixing patterns in children visiting pediatricians and family practitioners amplify the impact of increasing vaccine coverage. Conclusion Other high-income countries that introduced vaccine have not experienced biennial patterns, like the U.S. Our results suggest that increasing overall vaccine coverage to 85% among infants would lead to an overall reduction in incidence with annual epidemic patterns.
A telephone reminder to enhance adherence to interventions in cardiovascular randomized trials: A protocol for a study within a trial (SWAT)

The impact of reduced adherence in randomized clinical trials is well documented in the literature. Nonadherence can negatively affect the trial sample size and estimation of the treatment effect. This protocol aims to evaluate the effects of a telephone call reminder on the adherence rates of participants to interventions in a cardiovascular randomized trial. This is a study within a trial (SWAT). The host trial is evaluating the effectiveness of a multidisciplinary 16‐wk cardiovascular disease prevention program on risk factor profile among patients with carotid artery stenosis. Simultaneously, this SWAT will evaluate the effectiveness of telephone call reminders on the participants’ adherence to the host trial intervention. The primary outcome is adherence to the protocol of the host trial. Secondary outcomes are level of adherence, number of dropouts, and time to drop out from the host trial.
Metabolic Labeling of RNAs Uncovers Hidden Features and Dynamics of the Arabidopsis Transcriptome[CC-BY]

Metabolic RNA labeling coupled to RNA sequencing detects low-abundance RNAs and RNA processing intermediates, allowing for inhibitor-free RNA stability measurements in Arabidopsis seedlings. Transcriptome analysis by RNA sequencing (RNA-seq) has become an indispensable research tool in modern plant biology. Virtually all RNA-seq studies provide a snapshot of the steady state transcriptome, which contains valuable information about RNA populations at a given time but lacks information about the dynamics of RNA synthesis and degradation. Only a few specialized sequencing techniques, such as global run-on sequencing, have been used to provide information about RNA synthesis rates in plants. Here, we demonstrate that RNA labeling with the modified, nontoxic uridine analog 5-ethynyl uridine (5-EU) in Arabidopsis (Arabidopsis thaliana) seedlings provides insight into plant transcriptome dynamics. Pulse labeling with 5-EU revealed nascent and unstable RNAs, RNA processing intermediates generated by splicing, and chloroplast RNAs. Pulse-chase experiments with 5-EU allowed us to determine RNA stabilities without the need for chemical transcription inhibitors such as actinomycin and cordycepin. Inhibitor-free, genome-wide analysis of polyadenylated RNA stability via 5-EU pulse-chase experiments revealed RNAs with shorter half-lives than those reported after chemical inhibition of transcription. In summary, our results indicate that the Arabidopsis nascent transcriptome contains unstable RNAs and RNA processing intermediates and suggest that polyadenylated RNAs have low stability in plants. Our technique lays the foundation for easy, affordable, nascent transcriptome analysis and inhibitor-free analysis of RNA stability in plants.
SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy

Many recent studies have demonstrated the involvement of endoplasmic reticulum (ER) stress in the development of cardiac diseases and have suggested that modulation of ER stress response could be cardioprotective. Previously, we demonstrated that the deacetylase Sirtuin 1 (SIRT1) attenuates ER stress response and promotes cardiomyocyte survival. Here, we investigated whether and how autophagy plays a role in SIRT1-afforded cardioprotection against ER stress. The results revealed that protective autophagy was initiated before cell death in response to tunicamycin (TN)-induced ER stress in cardiac cells. SIRT1 inhibition decreased ER stress-induced autophagy, whereas its activation enhanced autophagy. In response to TN- or isoproterenol-induced ER stress, mice deficient for SIRT1 exhibited suppressed autophagy along with exacerbated cardiac dysfunction. At the molecular level, we found that in response to ER stress (i) the extinction of eEF2 or its kinase eEF2K not only reduced autophagy but further activated cell death, (ii) inhibition of SIRT1 inhibited the phosphorylation of eEF2, (iii) eIF2α co-immunoprecipitated with eEF2K, and (iv) knockdown of eIF2α reduced the phosphorylation of eEF2. Our results indicate that in response to ER stress, SIRT1 activation promotes cardiomyocyte survival by enhancing autophagy at least through activation of the eEF2K/eEF2 pathway.
In vivo Tissue Evaluation Reveals Improvements in Explicit PDT Dosimetry

Progress is needed before explicit photodynamic therapy (PDT) dosimetry can treat peritoneal carcinomatosis and yet spare all healthy tissue. A report by Cengel et al. in this issue of Photochemistry & Photobiology on tissue evaluation in a canine model may bring that goal a step closer and may even be dogma‐changing.
Early sexual dimorphism in the developing gut microbiome of northern elephant seals

The gut microbiome is an integral part of a species’ ecology, but we know little about how host characteristics impact its development in wild populations. Here, we explored the role of such intrinsic factors in shaping the gut microbiome of northern elephant seals during a critical developmental window of six weeks after weaning, when the pups stay ashore without feeding. We show that the early-life gut microbiome is already substantially different in male and female pups, even though males and females cannot yet be distinguished morphologically. Sex and age both explain around 15% of the variation in gut microbial beta diversity, while microbial communities sampled from the same individual show high levels of similarity across time, explaining another 40% of the variation. Only a small proportion of the variation in beta diversity is explained by health status, but healthy individuals have a greater microbial alpha diversity than their non-healthy peers. Across the post-weaning period, the elephant seal gut microbiome is highly dynamic. We found evidence for several colonisation and extinction events as well as a decline in Bacteriodes and an increase in Prevotella, a pattern that has previously been associated with the transition from nursing to solid food. Lastly, we show that genetic relatedness is correlated with gut microbiome similarity in males but not females, again reflecting substantial early sex-differences. Our study represents a naturally diet-controlled and longitudinal investigation of how intrinsic factors shape the early gut microbiome in a species with extreme sex differences in morphology and life history.
C2-H Arylation of indoles catalyzed by Palladium containing Metal-Organic-Framework (Pd-MOF) in bioderived γ-valerolactone (GVL).

Herein we report an efficient and selective procedure for the direct C2-H arylation of indoles using a Metal-Organic-Framework (MOF) containing palladium as heterogeneous catalyst and the non-toxic biomass derived solvent GVL (γ-valerolactone) as reaction medium. The developed method allows to reach excellent yields and C-2 selectivity and tolerates various substitutions on the indole scaffold. The established conditions ensure stability of the catalyst as well as recoverability, reusability and low metal leaching into solution.
Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.