Miracle-dz/UniFAR-FTUs huggingface dataset:
Management of Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Leukocyte- and Platelet-Rich Fibrin (L-PRF) and Photobiomodulation: A Retrospective Study

Background. The aim of this study was to compare retrospectively the effect of three different treatment protocols on the healing outcome in patients with established medication-related osteonecrosis of the jaw (MRONJ). Methods. A total of 34 MRONJ patients were recruited from the Department database and were divided according to the treatment protocols in a study group (G1) and two control groups (G2 and G3). G1 was treated with antibiotic therapy, surgery, leukocyte- and platelet-rich fibrin (L-PRF), and photobiomodulation; G2 was treated with antibiotic therapy and surgery; G3 was treated with antibiotic therapy and photobiomodulation. Various clinical variables and treatment protocols were analyzed to determine their correlation with the healing outcome at three and six months of follow-up. Results. There was a significant association between the different treatment protocols and the outcomes at both three and six months follow-up (p = 0.001 and p = 0.002, respectively). No significant association was observed between the outcomes and MRONJ localization, MRONJ stage, duration of drug treatment, gender, diabetes, corticosteroid therapy, smoking habits, underlying disease, and history of chemotherapy at both three and six months follow-up. Conclusions. Our results show that the combination of antibiotic therapy, surgery, L-PRF, and photobiomodulation may effectively contribute to MRONJ management.
Development of Compound Fault Diagnosis System for Gearbox Based on Convolutional Neural Network

Gear transmission is widely used in mechanical equipment. In practice, if the gearbox is damaged, it not only affects the yield rate but also damages other parts of machines; thus, increases the cost and difficulty of maintenance. With the advancement of technology, the concept of unmanned factories has been proposed; an automatic diagnosis system for the health management of gearboxes becomes necessary. In this paper, a compound fault diagnosis system for the gearbox based on convolutional neural network (CNN) is developed. Specifically, three-axis vibration signals measured by accelerometers are used as the input of the one-dimensional CNN; the detection of the existence and type of the fault is directly output. In testing, the model achieved nearly 100% accuracy on the fault samples we captured. Experimental evidence also shows that the frequency-domain data can provide better diagnostic results than the time-domain data due to the stable characteristics in the frequency spectrum. For practical usage, we demonstrated a remote fault diagnosis system through a local area network on an embedded platform. Furthermore, optimization of convolution kernels was also investigated. When moderately reducing the number of convolution kernels, it does not affect the diagnostic accuracy but greatly reduces the training time of the model.
PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells

The programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis blockade has been implemented in advanced-stage tumor therapy for various entities, including head and neck squamous cell carcinoma (HNSCC). Despite a promising tumor response in a subgroup of HNSCC patients, the majority suffer from disease progression. PD-L1 is known to influence several intrinsic mechanisms in cancer cells, such as proliferation, apoptosis, migration and invasion. Here, we modulated PD-L1 expression in three HNSCC cell lines with differential intrinsic PD-L1 expression. In addition to an alteration in the epithelial-to-mesenchymal transition (EMT) marker expression, we observed PD-L1-dependent cell spreading, migration and invasion in a spheroid spreading assay on four different coatings (poly-L-lysine, collagen type I, fibronectin and Matrigel®) and a chemotactic transwell migration/invasion assay. Furthermore, the overexpression of PD-L1 led to increased gene expression and small interfering ribonucleic acid (siRNA) knockdown and decreased gene expression of Rho-GTPases and related proteins in a RT2 Profiler™ PCR Array. Rac1 and Rho-GTPase pulldown assays revealed a change in the activation state concordantly with PD-L1 expression. In summary, our results suggest a major role for PD-L1 in favoring cell motility, including cell spreading, migration and invasion. This is presumably caused by altered N-cadherin expression and changes in the activation states of small Rho-GTPases Rho and Rac1.
Comparison of heart rate obtained from shorter duration Holter recordings to 24-hour mean heart rate in dogs with atrial fibrillation

The objective of this study was to evaluate the accuracy of short duration electrocardiographic (ECG) recordings extracted from ambulatory continuous ECG (Holter) to assess 24-hour mean heart rate in dogs with atrial fibrillation. In this retrospective study, Holter recordings obtained from 20 dogs with atrial fibrillation were selected for analysis. Ten out of 20 dogs were receiving drugs to control heart rate at the time of Holter evaluation. From the Holter recordings, heart rate averages were calculated for various sample durations (five-minutes, 30 minutes, one-hour, two-hours, and three-hours) for each dog. Percentage of these shorter duration ECG obtained HR averages that fell within ±10%, ±15% and ± 20% of 24-hour mean heart rate was determined for each sample duration and for each dog. Seventy five percent of heart rate averages obtained from three-hour ECG recordings fell within ±10% of 24-hour mean HR. All the heart rate averages obtained from two-hour ECG recordings fell within ±20% of 24-hour mean heart rate. Based on the results of this study it can be concluded that the duration of the ECG recording affects the prediction accuracy for 24-hour Holter mean HR. Only two and three hours of Holter recordings provided all heart rate averages within ±20% of 24-hour mean heart rate. No significant differences were noted in the prediction accuracy of shorter duration ECG recordings based on rate control therapy status. Further prospective studies are needed to assess the accuracy of HR obtained at home using various ECG recording devices to predict 24-hour mean heart rate in dogs with atrial fibrillation.
The evolutionary role of epigenetic mechanisms : the adaptation of freshwater organisms to climate change

Freshwater is a precious resource for humankind. Nevertheless, freshwater systems face not only significant anthropogenic pressure but also numerous transformations induced by climate change. Nowadays, climate change is recognized as a serious threat to freshwater ecosystems and, on a global scale, freshwater biodiversity is in rapid decline. In the last few years, epigenetics has been gaining importance in several scientific fields, such as human health and developmental biology. In fact, epigenetic mechanisms can influence phenotype determination and epigenetically acquired phenotypes are known to be inherited across several generations. Therefore, epigenetics is a promising but unexplored topic in a significant number of scientific fields. Taking into account that the global aim of this work was to explore the resilience of freshwater species to cope with the environmental transformations induced by climate change, its main specific objectives were: i) to review the impacts of climate change on freshwater ecosystems, and explore the link between epigenetic mechanisms and the adaptation of different species to the associated phenomena; ii) to assess the relevance of epigenetic mechanisms in the adaptation of Daphnia magna to an increase in water salinity. An extensive review was made leading to the conclusion that climate change is transforming the composition, biodiversity and functioning of numerous freshwater ecosystems. Additionally, this study highlighted that, in the context of climate change, the rise in water temperature and/or salinity are the major threats to freshwater biodiversity, while epigenetic mechanisms can have a decisive role in constraining both shortand long-term adaptation of different taxonomic groups to the environmental transformations induced by climate change. As the second objective was tackled, the exposure of one generation of Daphnia magna to increased salinity showed that there is a molecular adaptation to the hyperosmotic environment at the epigenetic level. For some genes, this epigenetic adaptation was transferred across three successive generations, none of which exposed to the stressor challenging the parental generation. Generally, this work supports the idea that epigenetic mechanisms are a promising topic in the fields of aquatic toxicology and evolutionary biology, as well as in research undertaken in their intersection.
Splicing machinery dysregulation drives glioblastoma development/aggressiveness: oncogenic role of SRSF3

Fuentes-Fayos et al. show that the expression of spliceosome components and splicing factors is dysregulated in high-grade astrocytomas and glioblastomas. The splicing machinery could be a new source of diagnostic and prognostic biomarkers as well as therapeutic targets, with SRSF3 being a key splicing factor in glioblastomas.
A Critical Review on Crystal Growth Techniques for Scalable Deposition of Photovoltaic Perovskite Thin Films

Although the efficiency of small-size perovskite solar cells (PSCs) has reached an incredible level of 25.25%, there is still a substantial loss in performance when switching from small size devices to large-scale solar modules. The large efficiency deficit is primarily associated with the big challenge of coating homogeneous, large-area, high-quality thin films via scalable processes. Here, we provide a comprehensive understanding of the nucleation and crystal growth kinetics, which are the key steps for perovskite film formation. Several thin-film crystallization techniques, including antisolvent, hot-casting, vacuum quenching, and gas blowing, are then summarized to distinguish their applications for scalable fabrication of perovskite thin films. In viewing the essential importance of the film morphology on device performance, several strategies including additive engineering, Lewis acid-based approach, solvent annealing, etc., which are capable of modulating the crystal morphology of perovskite film, are discussed. Finally, we summarize the recent progress in the scalable deposition of large-scale perovskite thin film for high-performance devices.
A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir

Hepatitis C virus (HCV) genotype 3 presents a high level of both baseline and acquired resistance to direct-acting antivirals (DAAs), particularly those targeting the NS5A protein. To understand this resistance we studied a cohort of Brazilian patients treated with the NS5A DAA, daclatasvir and the nucleoside analogue, sofosbuvir. We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. The effect of this substitution on both replication fitness and resistance to DAAs was evaluated using two genotype 3 subgenomic replicons. S98G had a modest effect on replication, but in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance. This result suggests that combinations of substitutions may drive a high level of DAA resistance and provide some clues to the mechanism of action of the NS5A-targeting DAAs.
Osteoglycin silencing exerts inhibitory effects on myocardial fibrosis and epithelial/endothelial‐mesenchymal transformation in a mouse model of myocarditis

Osteoglycin (Ogn), a class III SLRP member with multiple glycosylation sites, has been proposed to be engaged in cardiac dysfunction and adverse remodeling in human heart failure following myocardial infarction. However, the underlying mechanism remains to be elucidated. Thus, we sought to define the role of Ogn in regulation of the Wnt pathway on myocardial fibrosis and epithelial/endothelial‐mesenchymal transformation (EMT/EndMT) in mice with myocarditis. The pathological changes are observed, while hematoxylin–eosin staining and picric acid Sirius red staining were conducted in successfully constructed myocarditis mouse models. Immunohistochemistry and enzyme‐linked immunosorbent assay were adopted to determine Ogn and β‐catenin levels and serum procollagen propeptide concentrations in the mouse myocardial tissues, respectively. Expression of Ogn and Wnt signaling pathway‐related factors were measured by reverse transcription quantitative polymerase chain reaction and western blot assay, cell viability by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, and cell cycle distribution and apoptosis by flow cytometry. We saw indicative pathological changes accompanied by many Ogn and β‐catenin positive cells and increased serum procollagen propeptide, in the mouse myocardial tissues. Loss function assays showed reduced levels of Ogn, β‐catenin, LRP6, TGF‐β1, Twist, FSP‐1, α‐SMA and higher levels of E‐cadherin and VE‐cadherin, together with decreased proliferation rate, as well as increased apoptosis rate, indicating that the Wnt signaling pathway, proliferation were inhibited while apoptosis was enhanced with upon gene silencing. Coherently, depletion of Ogn inhibits myocardial fibroblasts proliferation and EMT/EndMT while facilitating myocardial fibroblasts apoptosis in myocarditis through the Wnt signaling pathway, thus serving as an intervention target for the molecular treatment of myocarditis.
The Safety and Efficacy of Phage Therapy for Superficial Bacterial Infections: A Systematic Review

Superficial bacterial infections, such as dermatological, burn wound and chronic wound/ulcer infections, place great human and financial burdens on health systems globally and are often complicated by antibiotic resistance. Bacteriophage (phage) therapy is a promising alternative antimicrobial strategy with a 100-year history of successful application. Here, we report a systematic review of the safety and efficacy of phage therapy for the treatment of superficial bacterial infections. Three electronic databases were systematically searched for articles that reported primary data about human phage therapy for dermatological, burn wound or chronic wound/ulcer infections secondary to commonly causative bacteria. Two authors independently assessed study eligibility and performed data extraction. Of the 27 eligible reports, eight contained data on burn wound infection (n = 156), 12 on chronic wound/ulcer infection (n = 327) and 10 on dermatological infections (n = 1096). Cautionary pooled efficacy estimates from the studies that clearly reported efficacy data showed clinical resolution or improvement in 77.5% (n = 111) of burn wound infections, 86.1% (n = 310) of chronic wound/ulcer infections and 94.14% (n = 734) of dermatological infections. Over half of the reports that commented on safety (n = 8/15), all published in or after 2002, did not express safety concerns. Seven early reports (1929–1987), described adverse effects consistent with the administration of raw phage lysate and co-administered bacterial debris or broth. This review strongly suggests that the use of purified phage to treat superficial bacterial infections can be highly effective and, by various routes of administration, is safe and without adverse effects.
The Microbial Composition in Circumneutral Thermal Springs from Chignahuapan, Puebla, Mexico Reveals the Presence of Particular Sulfur-Oxidizing Bacterial and Viral Communities

Terrestrial thermal springs are widely distributed globally, and these springs harbor a broad diversity of organisms of biotechnological interest. In Mexico, few studies exploring this kind of environment have been described. In this work, we explore the microbial community in Chignahuapan hot springs, which provides clues to understand these ecosystems’ diversity. We assessed the diversity of the microorganism communities in a hot spring environment with a metagenomic shotgun approach. Besides identifying similarities and differences with other ecosystems, we achieved a systematic comparison against 11 metagenomic samples from diverse localities. The Chignahuapan hot springs show a particular prevalence of sulfur-oxidizing bacteria from the genera Rhodococcus, Thermomonas, Thiomonas, Acinetobacter, Sulfurovum, and Bacillus, highlighting those that are different from other recovered bacterial populations in circumneutral hot springs environments around the world. The co-occurrence analysis of the bacteria and viruses in these environments revealed that within the Rhodococcus, Thiomonas, Thermonas, and Bacillus genera, the Chignahuapan samples have specific species of bacteria with a particular abundance, such as Rhodococcus erytropholis. The viruses in the circumneutral hot springs present bacteriophages within the order Caudovirales (Siphoviridae, Myoviridae, and Podoviridae), but the family of Herelleviridae was the most abundant in Chignahuapan samples. Furthermore, viral auxiliary metabolic genes were identified, many of which contribute mainly to the metabolism of cofactors and vitamins as well as carbohydrate metabolism. Nevertheless, the viruses and bacteria present in the circumneutral environments contribute to the sulfur cycle. This work represents an exhaustive characterization of a community structure in samples collected from hot springs in Mexico and opens opportunities to identify organisms of biotechnological interest.
Synthetic rewiring and boosting type I interferon responses for visualization and counteracting viral infections

Abstract Mammalian first line of defense against viruses is accomplished by the interferon (IFN) system. Viruses have evolved numerous mechanisms to reduce the IFN action allowing them to invade the host and/or to establish latency. We generated an IFN responsive intracellular hub by integrating the synthetic transactivator tTA into the chromosomal Mx2 locus for IFN-based activation of tTA dependent expression modules. The additional implementation of a synthetic amplifier module with positive feedback even allowed for monitoring and reacting to infections of viruses that can antagonize the IFN system. Low and transient IFN amounts are sufficient to trigger these amplifier cells. This gives rise to higher and sustained—but optionally de-activatable—expression even when the initial stimulus has faded out. Amplification of the IFN response induced by IFN suppressing viruses is sufficient to protect cells from infection. Together, this interfaced sensor/actuator system provides a toolbox for robust sensing and counteracting viral infections.
On-Demand Detachment of Succinimides on Cysteine to Facilitate (Semi)Synthesis of Challenging Proteins

The maleimide group is a widely used reagent for bioconjugation of peptides, proteins, and oligonucleotides employing Michael addition and Diels–Alder cycloaddition reactions. However, the utility of this functionality in chemical synthesis of peptides and proteins remains unexplored. We report, for the first time that PdII complexes can mediate the efficient removal of various succinimide derivatives in aqueous conditions. Succinimide removal by PdII was applied for the synthesis of two ubiquitin activity-based probes (Ub-ABPs) employing solid phase chemical ligation (SPCL). SPCL was achieved through a sequential three segment ligation on a polymer support via a maleimide anchor. The obtained probes successfully formed the expected covalent complexes with deubiquitinating enzymes (DUBs) USP2 and USP7, highlighting the use of our new method for efficient preparation of unique synthetic proteins. Importantly, we demonstrate the advantages of our newly developed method for the protection and deprotection of native cysteine with a succinimide group in a peptide fragment derived from thioredoxin-1 (Trx-1) obtained via intein based expression to enable ligation/desulfurization and subsequent disulfide bond formation in a one-pot process.
A novel homozygous frameshift mutation in the DCC gene in a Pakistani family with autosomal recessive horizontal gaze palsy with progressive scoliosis‐2 with impaired intellectual development

Horizontal Gaze Palsy with Progressive Scoliosis‐2 with Impaired Intellectual Development (HGPPS2) is a rare congenital disorder characterized by absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence. We report three new patients with HGPPS2 in a consanguineous Pakistani family, presenting varying degrees of progressive scoliosis, developmental delays, horizontal gaze palsy, agenesis of corpus callosum, and absence of cerebral commissures. Analysis of genotyping data identified shared loss of heterozygosity (LOH) region on chromosomes 5p15.33‐15.31, 6q11.2‐12, and 18q21.1‐21.3. A hypothesis‐free, unbiased exome data analysis detected an insertion of nucleotide A (c.2399dupA) in exon 16 of the DCC gene. The insertion is predicted to cause frameshift p.(Asn800Lysfs*11). Interestingly, DCC gene is present in the LOH region on chromosome 18. Variant (c.2399dupA) in the DCC gene is considered as the most probable candidate variant for HGPPS2 based on the presence of DCC in the LOH region, previously reported role of DCC in HGPPS2, perfect segregation of candidate variant with the disease, prediction of variant pathogenicity, and absence of variant in variation databases. Sanger Sequencing confirmed the presence of the novel homozygous mutation in all three patients; the parents were heterozygous carriers of the mutation, in accordance with an autosomal recessive inheritance pattern. DCC encodes a netrin‐1 receptor protein; its role in the development of the CNS has recently been established. Biallelic DCC mutations have previously been shown to cause HGPPS2. A novel homozygous variant in patients of the reported family extend the genotypic and phenotypic spectrum of HGPPS2.
Chondrocyte‐to‐osteoblast transformation in mandibular fracture repair

The majority of fracture research has been conducted using long bone fracture models, with significantly less research into the mechanisms driving craniofacial repair. However, craniofacial bones differ from long bones in both their developmental mechanism and embryonic origin. Thus, it is possible that their healing mechanisms could differ. In this study we utilize stabilized and unstabilized mandible fracture models to investigate the pathways regulating repair. Whereas fully stable trephine defects in the ramus form bone directly, mechanical motion within a transverse fracture across the same anatomical location promoted robust cartilage formation before boney remodeling. Literature investigating long bone fractures show chondrocytes are a direct precursor of osteoblasts during endochondral repair. Lineage tracing with Aggrecan‐CreERT2::Ai9 tdTomato mice demonstrated that mandibular callus chondrocytes also directly contribute to the formation of new bone. Furthermore, immunohistochemistry revealed that chondrocytes located at the chondro‐osseous junction expressed Sox2, suggesting that plasticity of these chondrocytes may facilitate this chondrocyte‐to‐osteoblast transformation. Based on the direct role chondrocytes play in bone repair, we tested the efficacy of cartilage grafts in healing critical‐sized mandibular defects. Whereas empty defects remained unbridged and filled with fibrous tissue, cartilage engraftment produced bony‐bridging and robust marrow cavity formation, indicating healthy vascularization of the newly formed bone. Engrafted cartilage directly contributed to new bone formation since a significant portion of the newly formed bone was graft/donor‐derived. Taken together these data demonstrate the important role of chondrocyte‐to‐osteoblast transformation during mandibular endochondral repair and the therapeutic promise of using cartilage as a tissue graft to heal craniofacial defects.