Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitrosative Stress Biomarkers in the Non-Stimulated and Stimulated Saliva, as well as Gingival Crevicular Fluid of Patients with Periodontitis: Review and Clinical Study

Diagnosis of periodontopathy is complex and includes defining the cause, type, stage, and grade of periodontitis. Therefore, alternative diagnostic methods are sought to indicate the progression of inflammation or to determine the effectiveness of therapy. Gingival crevicular fluid (GCF) biomarkers can be particularly useful because they most likely reflect the disease process of the periodontal tissues. However, the difficulty of collecting GCF for testing is the reason for the limited use in diagnostics. Because periodontitis is the primary source of nitrogen free radicals in the oral cavity, the aim of the study was to evaluate the biomarkers of nitrosative stress (nitric oxide, peroxynitrite, and S-nitrosothiols) in GCF, non-stimulated and stimulated saliva of 90 patients with periodontitis. The study group was divided into two subgroups, depending on the stage of the disease severity. We showed a significantly higher concentration of all assessed biomarkers in the non-stimulated and stimulated saliva of patients with periodontitis. However, significant changes in GCF has been shown only for peroxynitrite. The studied biomarkers did not correlate with clinical periodontal status, which probably results from their short-duration activity and the impact on a few factors in the oral cavity. Saliva and gingival fluid are not very useful in the differential diagnosis of periodontitis.
Transforaminal Epidural Balloon Adhesiolysis via a Contralateral Interlaminar Retrograde Foraminal Approach: A Retrospective Analysis and Technical Considerations

Several treatment modalities have been proposed for foraminal stenosis, but the treatment options remain unsatisfactory. Previous studies have shown that transforaminal balloon adhesiolysis may be effective in patients with refractory lumbar foraminal stenosis. However, in patients with a high iliac crest, balloon catheter insertion may be difficult via a conventional transforaminal approach (particularly targeting the L5–S1 foramen). It has been reported that an epidural catheter can be placed easily by a contralateral interlaminar retrograde foraminal approach. Therefore, we applied this approach to L5–S1 transforaminal balloon adhesiolysis in patients with a high iliac crest. We retrospectively analyzed data from 22 patients who underwent combined epidural adhesiolysis and balloon decompression (balloon adhesiolysis) using the novel foraminal balloon catheter via a contralateral interlaminar retrograde foraminal approach. The pain intensity significantly decreased over the three-month period after balloon adhesiolysis (p < 0.001). There were no complications associated with the balloon procedure. The present study suggests that balloon adhesiolysis for L5-S1 foramen via a contralateral interlaminar retrograde foraminal approach may be an effective alternative for patients with a high iliac crest and refractory lumbar radicular pain due to lumbar foraminal stenosis. In addition, detailed procedural aspects are described here.
Activation of a Subset of Evolutionarily Young Transposable Elements and Innate Immunity Are Linked to Clinical Responses to 5-Azacytidine

Activation of specific classes of evolutionarily young transposable elements can lead to activation of the innate immune system. The DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2-deoxycytidine have been approved for the treatment of different types of hematologic malignancies. However, only about 50% of patients respond to treatment. Therefore, a more comprehensive understanding of the molecular changes in patients treated with DNMTi is needed. Here, we examined gene expression profiles in a total of 150 RNA samples from two adult cohorts and one pediatric cohort with hematologic cancers taken before, during, and after treatment with 5-azacytidine (40 patients; 15 nonresponders, 25 responders). Using each patient as their own control, malignant cells showed preferential activation of a subset of evolutionarily young transposable elements (TE), including endogenous retroviral long terminal repeats (LTR), short and long interspersed nuclear elements (SINE and LINE), and the type I IFN pathway in responders, all independent of disease classification. Transfection of eight upregulated LTRs into recipient human cells in culture showed robust and heterogenous activation of six genes in the type I IFN pathway. These results, obtained in diverse hematologic disease entities, show that common targets (TE) activated by the same drug (5-azacytidine) elicit an immune response, which may be important for patient's responses to DNMTi. Significance: Activation of specific classes of evolutionarily young transposable elements can lead to activation of the innate immune system.
Regulation of the Single Polar Flagellar Biogenesis

Some bacterial species, such as the marine bacterium Vibrio alginolyticus, have a single polar flagellum that allows it to swim in liquid environments. Two regulators, FlhF and FlhG, function antagonistically to generate only one flagellum at the cell pole. FlhF, a signal recognition particle (SRP)-type guanosine triphosphate (GTP)ase, works as a positive regulator for flagellar biogenesis and determines the location of flagellar assembly at the pole, whereas FlhG, a MinD-type ATPase, works as a negative regulator that inhibits flagellar formation. FlhF intrinsically localizes at the cell pole, and guanosine triphosphate (GTP) binding to FlhF is critical for its polar localization and flagellation. FlhG also localizes at the cell pole via the polar landmark protein HubP to directly inhibit FlhF function at the cell pole, and this localization depends on ATP binding to FlhG. However, the detailed regulatory mechanisms involved, played by FlhF and FlhG as the major factors, remain largely unknown. This article reviews recent studies that highlight the post-translational regulation mechanism that allows the synthesis of only a single flagellum at the cell pole.
Host Plants Influence the Symbiont Diversity of Eriosomatinae (Hemiptera: Aphididae)

Eriosomatinae is a particular aphid group with typically heteroecious holocyclic life cycle, exhibiting strong primary host plant specialization and inducing galls on primary host plants. Aphids are frequently associated with bacterial symbionts, which can play fundamental roles in the ecology and evolution of their host aphids. However, the bacterial communities in Eriosomatinae are poorly known. In the present study, using high-throughput sequencing of the bacterial 16S ribosomal RNA gene, we surveyed the bacterial flora of eriosomatines and explored the associations between symbiont diversity and aphid relatedness, aphid host plant and geographical distribution. The microbiota of Eriosomatinae is dominated by the heritable primary endosymbiont Buchnera and several facultative symbionts. The primary endosymbiont Buchnera is expectedly the most abundant symbiont across all species. Six facultative symbionts were identified. Regiella was the most commonly identified facultative symbiont, and multiple infections of facultative symbionts were detected in the majority of the samples. Ordination analyses and statistical tests show that the symbiont community of aphids feeding on plants from the family Ulmaceae were distinguishable from aphids feeding on other host plants. Species in Eriosomatinae feeding on different plants are likely to carry different symbiont compositions. The symbiont distributions seem to be not related to taxonomic distance and geographical distance. Our findings suggest that host plants can affect symbiont maintenance, and will improve our understanding of the interactions between aphids, their symbionts and ecological conditions.
Data-Driven Respiratory Gating Outperforms Device-Based Gating for Clinical 18F-FDG PET/CT

A data-driven method for respiratory gating in PET has recently been commercially developed. We sought to compare the performance of the algorithm with an external, device-based system for oncologic 18F-FDG PET/CT imaging. Methods: In total, 144 whole-body 18F-FDG PET/CT examinations were acquired, with a respiratory gating waveform recorded by an external, device-based respiratory gating system. In each examination, 2 of the bed positions covering the liver and lung bases were acquired with a duration of 6 min. Quiescent-period gating retaining approximately 50% of coincidences was then able to produce images with an effective duration of 3 min for these 2 bed positions, matching the other bed positions. For each examination, 4 reconstructions were performed and compared: data-driven gating (DDG) (we use the term DDG-retro to distinguish that we did not use the real-time R-threshold–based application of DDG that is available within the manufacturer’s product), external device-based gating (real-time position management (RPM)–gated), no gating but using only the first 3 min of data (ungated-matched), and no gating retaining all coincidences (ungated-full). Lesions in the images were quantified and image quality scored by a radiologist who was masked to the method of data processing. Results: Compared with the other reconstruction options, DDG-retro increased the SUVmax and decreased the threshold-defined lesion volume. Compared with RPM-gated, DDG-retro gave an average increase in SUVmax of 0.66 ± 0.1 g/mL (n = 87, P < 0.0005). Although the results from the masked image evaluation were most commonly equivalent, DDG-retro was preferred over RPM-gated in 13% of examinations, whereas the opposite occurred in just 2% of examinations. This was a significant preference for DDG-retro (P = 0.008, n = 121). Liver lesions were identified in 23 examinations. Considering this subset of data, DDG-retro was ranked superior to ungated-full in 6 of 23 (26%) cases. Gated reconstruction using the external device failed in 16% of examinations, whereas DDG-retro always provided a clinically acceptable image. Conclusion: In this clinical evaluation, DDG-retro provided performance superior to that of the external device-based system. For most examinations the performance was equivalent, but DDG-retro had superior performance in 13% of examinations, leading to a significant preference overall.
Enhanced shrub growth in the Arctic increases habitat connectivity for browsing herbivores

Habitat connectivity is a key factor influencing species range dynamics. Rapid warming in the Arctic is leading to widespread heterogeneous shrub expansion, but impacts of these habitat changes on range dynamics for large herbivores are not well understood. We use the climate–shrub–moose system of northern Alaska as a case study to examine how shrub habitat will respond to predicted future warming, and how these changes may impact habitat connectivity and the distribution of moose (Alces alces). We used a 19 year moose location dataset, a 568 km transect of field shrub sampling, and forecasted warming scenarios with regional downscaling to map current and projected shrub habitat for moose on the North Slope of Alaska. The tall‐shrub habitat for moose exhibited a dendritic spatial configuration correlated with river corridor networks and mean July temperature. Warming scenarios predict that moose habitat will more than double by 2099. Forecasted warming is predicted to increase the spatial cohesion of the habitat network that diminishes effects of fragmentation, which improves overall habitat quality and likely expands the range of moose. These findings demonstrate how climate change may increase habitat connectivity and alter the distributions of shrub herbivores in the Arctic, including creation of novel communities and ecosystems.
Elevated p38MAPK activity promotes neural stem cell aging

Age-progressive neural stem cell (NSC) dysfunction leads to impaired neurogenesis, cognitive decline and the onset of age-related neurodegenerative pathologies. p38MAPK signalling pathway limits stem cell activity during aging in several tissues. Its role in NSCs remains controversial. In this work, we show that p38MAPK activity increases in NSCs with age in the subventricular zone (SVZ) and its pharmacological inhibition is sufficient to rejuvenate their activity in vitro. These data reveal a cell-autonomous role for p38MAPK increase in decreasing NSC homeostasis with age. This information shed light in the role of p38MAPK in NSC aging.
The Cuprizone Model: Dos and Do Nots

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Various pre-clinical models with different specific features of the disease are available to study MS pathogenesis and to develop new therapeutic options. During the last decade, the model of toxic demyelination induced by cuprizone has become more and more popular, and it has contributed substantially to our understanding of distinct yet important aspects of the MS pathology. Here, we aim to provide a practical guide on how to use the cuprizone model and which pitfalls should be avoided.
The Glucocorticoid Receptor NR3C1 in Testicular Peritubular Cells is Developmentally Regulated and Linked to the Smooth Muscle-Like Cellular Phenotype

Whether glucocorticoids (GC) can directly affect human testicular functions is not well understood. A predominant site of GC receptor (GR; NR3C1) expression in the adult testis are peritubular smooth muscle-like cells, which express smooth muscle actin (ACTA2), contract and thereby are involved in sperm transport. In contrast to the adult, neither GR nor ACTA2, or elastin (ELN) were detected in the peritubular compartment before puberty in non-human primate testes. In isolated human testicular peritubular cells (HTPCs), activation of GR by dexamethasone (Dex) caused the translocation of GR to the nucleus and stimulated expression of ACTA2 and ELN, without affecting the expression of collagens. Cytoskeletal ACTA2-rearrangements were observed and were associated with an increased ability to contract. Our results indicate post-pubertal testicular roles of GC in the maintenance of the contractile, smooth muscle-like phenotype of peritubular cells.
Antibody-Drug Conjugate Using Ionized Cys-Linker-MMAE as the Potent Payload Shows Optimal Therapeutic Safety

Monomethyl auristatin E (MMAE) is the most popular and widely used cytotoxin in the development of antibody-drug conjugates (ADCs). However, current MMAE-based ADCs are all constructed using cleavable linkers, and this design concept still has insurmountable drawbacks. Their potential instabilities and lipophilic MMAE-induced “bystander effect” inevitably increase the toxicity to normal tissues. Herein, we overturn previous negative views of MMAE-based ADCs with non-cleavable linkers and propose using ionized L-Cysteine (Cys)-linker-MMAE as a novel payload, which can ingeniously enrich and enter tumor cells through receptor-mediated endocytosis of antibodies while its lower permeability helps to avoid further off-target toxicity. We demonstrate that Cys-linker-MMAE maintains high potency similar to free MMAE at the tubulin molecular level and can also be efficiently released in target cells. As a result, the preferred ADC (mil40-15) not only exhibits ideal plasma stability and maintains potent cytotoxicity as MMAE (IC50: 10−11 M), but also shows improved safety with lower bystander toxicity (IC50: 10−9 M), its maximum tolerated dose approaching the level of the naked antibody (160 mg/kg). This study indicated that Cys-linker-MMAE has the potential as a potent payload for ADCs, which is expected to provide novel strategies for the development of MMAE-based ADCs.
Recent Advances in Printed Capacitive Sensors

In this review paper, we summarize the latest advances in the field of capacitive sensors fabricated by printing techniques. We first explain the main technologies used in printed electronics, pointing out their features and uses, and discuss their advantages and drawbacks. Then, we review the main types of capacitive sensors manufactured with different materials and techniques from physical to chemical detection, detailing the main substrates and additives utilized, as well as the measured ranges. The paper concludes with a short notice on status and perspectives in the field.
Degree of Conversion Contributes to Dentin Bonding Durability of Contemporary Universal Adhesives.

PURPOSE The objectives of this study were to evaluate the micro-tensile bond strength (μTBS) of five contemporary universal adhesives to dentin after 24 hours and thermocycling (TC), to measure their degrees of conversion (DC) and to test the correlation between μTBS and DC. METHODS AND MATERIALS Four commercially available universal adhesives, Prime&Bond universal (PBU), Ecosite Bond (EB), G-Premio Bond (GPB), and Clearfil Universal Bond Quick (UBQ), and one experimental adhesive, UBQ without an amide monomer (UBQ-A), were used in this study. For the μTBS test, midcoronal dentin of 50 human molars was exposed, ground using 600-grit SiC paper, and the adhesives were applied according to the manufacturers' instructions. After resin-composite buildup and 24-hour water storage, one-half of the specimens were subjected to 15,000 thermal cycles. The specimens were sectioned into beams and stressed in tension at a crosshead speed of 1 mm/min until failure. The DC of adhesives applied to dentin was evaluated using attenuated total reflectance Fourier-transform infrared spectroscopy immediately after light-curing. All data were statistically analyzed at a significance level of 0.05. RESULTS The highest μTBSs were obtained with UBQ, UBQ-A, and PBU, which were not significantly different from each other both after 24 hours and TC. The μTBS of GPB was lower compared with the aforementioned adhesives, but significantly only after TC, and the lowest μTBSs were obtained with EB. TC did not affect the μTBSs of UBQ, UBQ-A, and PBU significantly, but a significant decrease was observed with GPB and EB. The highest DC was obtained with PBU and UBQ, followed by 2-hydroxyethyl methacrylate-rich adhesives UBQ-A and EB, which exhibited significantly lower DCs. The DC of GPB could not be determined because the reference peak at 1608 cm-1 was not detected in its spectra. A significant positive correlation was shown between μTBS and DC after 24 hours (r=0.716) and TC (r=0.856). CONCLUSION μTBS and DC were positively correlated, more markedly after TC, which suggests that DC may be an important factor for bond durability.
Internet Access and Utilization among Medical Undergraduate and Post Graduate Students of a Medical College in Madhya Pradesh

Results: A total of 507 UG & 127 PG students were approached and 386(76%) UG, 119(93%) PG’s completed the questionnaires. Majority of the respondents (87.0%) reported having knowledge of internet use. About 365(72%) of the study subjects own computer, being significantly higher among PG’s (89%0 as compared to UG’s (67%). Main purpose of using internet as cited by UG’s was email/chatting (74%), where as dissertation work was main purpose among PG (66%). Slow speed of internet was the main problem faced by the subjects 299(595) while accessing the website.
Reference ranges and trajectories for blood pressure in pregnancy: findings from a follow-up study based on China Maternal and Newborn’s Health Monitoring System

ABSTRACT Objectives: This study aimed to establish normal blood pressure reference ranges across gestation and maternal characteristics. Methods: We conducted a follow-up study including 29,200 Chinese normal pregnant women. Multilevel restrictive cubic spline models were used to calculate normal blood pressure reference ranges among all population and stratified groups. Results: In all normal pregnancies, the normal reference range of systolic blood pressure were 93.94-118.74 mmHg(2.5th-97.5th) and 97.35-124.63 mmHg at 12 and 37 weeks gestation, respectively while 58.79-74.21 mmHg and 59.19-78.25 mmHg were for diastolic blood pressure at 12 and 37 weeks gestation, which differed in subgroups stratified by prepregnancy body mass index and maternal age. Conclusion: This study provides evidence for blood pressure management in Chinese pregnant women.
The electrocardiogram in the diagnosis and management of patients with dilated cardiomyopathy

The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. In approximately one third of cases, DCM is familial with a genetic pathogenesis and various patterns of inheritance. Although the electrocardiogram (ECG) has been considered traditionally non‐specific in DCM, the recently acquired knowledge of the genotype–phenotype correlations provides novel opportunities to identify patterns and abnormalities that may point toward specific DCM subtypes. A learned ECG interpretation in combination with an appropriate use of other ECG‐based techniques including ambulatory ECG monitoring, exercise tolerance test and imaging modalities, such as echocardiography and cardiovascular magnetic resonance, may allow the early identification of specific genetic or acquired forms of DCM. Furthermore, ECG abnormalities may reflect the severity of the disease and provide a useful tool in risk stratification and management. In the present review, we discuss the current role of the ECG in the diagnosis and management of DCM. We describe various clinical settings where the appropriate use and interpretation of the ECG can provide invaluable clues, contributing to the important role of this basic tool as cardiovascular medicine evolves.
Adult kidneys shrink to fit paediatric recipients

Size mismatch between donor and recipient in solid organ transplantation can add significant morbidity and mortality to the recipient (1). However due to the scarcity of both deceased donors, as well as suitable living donors, discrepancies between the size and weight of the donor, compared with the recipient are often a necessity, if solid organ transplantation is to proceed in a particular individual.
Management of heart failure and type 2 diabetes mellitus: Maximizing complementary drug therapy

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and occurs in ~25% of patients with heart failure (HF). Patients with co‐morbid HF and T2DM are at elevated risk of adverse outcomes, making optimization of complementary drug therapies essential. While research is ongoing, recent advances in drug therapy, including the introduction of sacubitril/valsartan for HF with reduced ejection fraction and the finding of positive cardiovascular effects of glucose‐lowering agents (particularly sodium‐glucose co‐transporter‐2 [SGLT2] inhibitors) have the potential to transform pharmacologic management of co‐morbid HF and T2DM. In this review, we provide a comprehensive overview of cardiovascular clinical trials of therapies for HF and diabetes mellitus to date and identify areas requiring further investigation. We also discuss the pathophysiologic overlap of the two diseases and explore the complementary therapeutic effects of HF and T2DM drugs, with a particular focus on sacubitril/valsartan and SGLT2 inhibitors.