bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed Soft Tissue Changes after Clockwise Rotation of the Maxillo-Mandibular Complex
Authors: Kwon Jin-Ju , Kang Young-Hoon , Hwang Dae-Seok 
Published: February 2022

Objective:
The purpose of this study was to evaluate delayed soft tissue changes of the maxilla-mandibular complex MMC using three-dimensional (3D) cone-beam computed tomography after clockwise repositioning orthognathic surgery.

Methods:
This study included 21 patients that underwent maxilla-mandibular complex clockwise rotational orthognathic surgery by 1 doctor from January 2015 to June 2019. Radiographic images (panorama, lateral cephalogram, posteroanterior view, and conebeam computed tomography) were taken and 3D analysis was performed using the Invivo 5 (Anatomage Inc, Santa Clara, CA) to acquire 3D images before surgery, immediately after surgery, at 6 months after surgery and 21 months after surgery. The 9 soft tissue landmarks were measured and compared in terms of postoperative changes in transverse, vertical, and anteroposterior directions. The points were at the outer commissure of the eye fissure (Exocathion; Exc_r, Exc_l), at the midline of both the nasal root and the nasofrontal suture, analogous to bony N (soft tissue nasion; N), the most prominent point on the nasal tip (Pronasale; Prn), the most lateral point in the curved baseline of each ala, indicating the facial insertion of the nasal wing base (Alare curvature; Ac_r, Ac_l), the most lateral point on the soft tissue contour of each mandibular angle (Soft tissue Gonion; Go_r, Go_l), and the most inferior midpoint on the soft tissue contour of the chin (soft tissue menton; Me).

Results:
The most prominent point of the nasal tip (Prn) moved 1.36 mm upward and 1.55 mm forward in the vertical and anteroposterior planes immediately after surgery. However, there were no significant changes in Ac_r and Ac_l even immediately after surgery. Both soft tissue gonions shifted downward and forward between immediately after surgery and 6 months after surgery. However, no significant change was observed in the value of any of the 9 soft tissue points between 6 months and 21 months after surgery (P value < 0.05).

Conclusions:
No significant changes were observed between 6 and 21 months after surgery, which suggests no delayed soft tissue changes occur in surgically treated patients after the resolution of surgically-related facial edema and swelling and postsurgical remodeling of hard tissue in overlying soft tissue.
Simultaneous Management of Condylar Osteochondroma and Secondary Malformation With a New Intraoral Approach
Authors: Zheng Li Wu , Dong Shi Ying , Li Jing Wen , Wu Zhong Xing 
Published: February 2022

Purpose:
The present study aimed to investigate the clinical efficacy of simultaneous management of condylar osteochondroma and its secondary dentofacial deformities using an intraoral surgical approach.

Methods:
Six patients with condylar osteochondroma were treated with intraoral vertical ramus osteotomies and condylar resection. The free rising branch was used for reconstructing the temporomandibular joint. The simultaneous orthognathic surgery and plastic surgery were performed sequentially to correct the secondary dentofacial deformities. The indexes of aesthetic symmetry, occlusion relationship, temporomandibular joint function, condylar height, and volume change were assessed in the subsequential follow up.

Results:
The mean follow up period was 31 months. All patients had no tumor recurrence. The ipsilateral joint function, occlusal relationship, and facial symmetry were satisfied. The ipsilateral condylar reconstruction had no obvious bone resorption and the ramus height was maintained well. Postoperative assessment showed the preoperative design was accurately fulfilled.

Conclusions:
The simultaneous condylar osteochondroma resection and temporomandibular joint reconstruction using intraoral approach avoids extraoral scars and correct facial asymmetry without compromising the long-term joint function and occlusal relationship.
Transnasal Medial Canthopexy Supported with Autogenous Bone Graft: A New Method for Repair of Traumatic Telecanthus
Authors: Abdelmegeed Ahmed Gaber , Haredy Mostafa Mamdoh , Mazeed Ahmed S. , Hifny Mahmoud A. 
Published: February 2022

Introduction:
The medial canthus is an important structure to maintain the shape of the eye and assist in drainage of the lacrimal sac. Traumatic telecanthus is a difficult deformity to treat which involves both esthetic and functional aspects. Transnasal wiring remains the gold standard for repair of the medial canthal tendon (MCT) avulsion; however, it is often complicated by canthal drift, extrusion of wires, and in-fracture of the contralateral orbital bones from pressure by tied wires. In order to overcome traditional transnasal wiring technique pitfalls, this study proposes a transnasal wiring fixation method supported with a bone graft to treat patients presenting with telecanthus following complex nasoorbitoethmoid fractures.

Patients and Methods:
From December 2018 to October 2020, 12 patients with traumatic telecanthus underwent transnasal wiring fixation of the MCT supported with bone graft. The wire holding the MCT was delivered through a single hole to the contralateral side and secured to a small bone graft by passing the wire through 2 holes in the graft in a button-like fashion. Then the wire end is pulled again to the affected side through the same hole and the 2 wires ends are tightly twisted after setting the MCT posterior to the lacrimal crest.

Results:
Restoration of the MCT to its normal position was achieved in all patients. There were no observed major complications. Only 2 cases of wound infection and 1 case of dacrocystitis were encountered, which settled with conservative management. The preoperative palpebral fissure width (mean: 28.33mm ± 2.188mm) was significantly lower than the postoperative palpebral fissure width (mean: 34.17mm ± 1.03mm) (P<0.05).

Conclusions:
This study introduces a modified technique of transnasal wiring fixation to restore palpebral shape and intercanthal distance. The proposed technique could eliminate most of the frequently observed complications of the traditional methods.
Transcriptomic analysis of aging mouse sciatic nerve reveals early pathways leading to sarcopenia
Authors: Comfort Nicole , Gade Meethila , Strait Madeleine , Merwin Samantha J. , Antoniou Daphne , Memou Anna , Rideout Hardy J. , Corti Stefania , Kariya Shingo , Re Diane B. 
Published: February 2022

AbstractBackgroundSarcopenia, the age-associated decline in skeletal muscle mass and strength, has long been considered a disease of muscle only, but accumulating evidence suggests that sarcopenia could originate from the neural components controlling muscles. To identify early molecular changes in the efferent nerves that may drive sarcopenia initiation, we performed a longitudinal transcriptomic analysis of the sciatic nerve in aging mice.MethodsSciatic nerve and gastrocnemius muscle were obtained from young adult, middleaged, old, and sarcopenic (5,18, 21 and 24 months old, respectively) C57BL/6J female mice (n=6 per age group). Sciatic nerve RNA was extracted and subjected to RNA sequencing (RNA-seq), with real-time quantitative reverse transcription PCR (qRT-PCR) validation of differentially expressed genes (DEGs). Functional enrichment analysis of clusters of genes associated with patterns of gene expression across age groups was performed. Sarcopenia was confirmed with qRT-PCR of previously established markers of sarcopenia onset in gastrocnemius muscle.ResultsWe detected 33 significant DEGs in sciatic nerve of 18-month-old mice compared to 5-month-old mice (absolute value of fold change > 2; false discovery rate [FDR] < 0.05) which we validated with qRT-PCR of the three top up- and down-regulated genes. Up-regulated genes were associated with circadian rhythm and the AMPK signaling pathway, while down-regulated genes were associated with biosynthesis and metabolic pathways and circadian rhythm. Strikingly, we detected a significant increase in Myog expression (log2 fold change = 18.93, FDR q-value = 1.54×10−12) in sciatic nerve of 18-month-old mice, before up-regulation in muscle was observed. We identified seven clusters of genes with similar expression patterns across groups. Functional enrichment analysis of these clusters revealed biological processes that may be implicated in sarcopenia initiation including extracellular matrix organization and circadian regulation of gene expression.ConclusionsGene expression changes in mouse peripheral nerve can be detected prior to overt clinical onset of sarcopenia. These early molecular changes we report shed a new light on biological processes that may be implicated in sarcopenia initiation and pathogenesis. Future studies will validate which of the key changes we reported have disease modifying and/or biomarker potential.
Effects of clozapine-N-oxide and compound 21 on sleep in laboratory mice
Authors: Traut Janine , Mengual Jose Prius , Meijer Elise J. , McKillop Laura E. , Alfonsa Hannah , Hoerder-Suabedissen Anna , Song Seoho Michael , Molnár Zoltán , Akerman Colin J. , Vyazovskiy Vladyslav V. , Krone Lukas B. 
Published: February 2022

AbstractDesigner Receptors Exclusively Activated by Designer Drugs (DREADDs) are chemogenetic tools for remote control of targeted cell populations using chemical actuators that bind to modified receptors. Despite the popularity of DREADDs in neuroscience and sleep research, potential effects of the DREADD actuator clozapine-N-oxide (CNO) on sleep have never been systematically tested. Here we show that intraperitoneal injections of commonly used CNO doses (1, 5, and 10 mg/kg) alter sleep in wild-type male laboratory mice. Using electroencephalography (EEG) and electromyography (EMG) to analyse sleep, we found a dose-dependent suppression of rapid eye-movement (REM) sleep, changes in EEG spectral power during non-REM (NREM) sleep, and altered sleep architecture in a pattern previously reported for clozapine. Effects of CNO on sleep could arise from back-metabolism to clozapine or binding to endogenous neurotransmitter receptors. Interestingly, we found that the novel DREADD actuator, compound 21 (C21, 3 mg/kg), similarly modulates sleep despite a lack of back-metabolism to clozapine. Our results demonstrate that both CNO and C21 can modulate sleep of mice not expressing DREADD receptors. This implies that back-metabolism to clozapine is not the sole mechanism underlying side effects of chemogenetic actuators. Therefore, any chemogenetic experiment should include a DREADD-free control group injected with the same CNO, C21 or newly developed actuator. We suggest that electrophysiological sleep assessment could serve as a sensitive tool to test the biological inertness of novel chemogenetic actuators.
Epigenetic cell memory: The gene’s inner chromatin modification circuit
Authors: Bruno Simone , Williams Ruth J. , Del Vecchio Domitilla 
Published: February 2022

AbstractEpigenetic cell memory allows distinct gene expression patterns to persist in different cell types despite a common genotype. Although different patterns can be maintained by the concerted action of transcription factors (TFs), it was proposed that long-term persistence hinges on chromatin state. Here, we study how the dynamics of chromatin state affect memory, and focus on a biologically motivated circuit motif, among histones and DNA modifications, that mediates the action of TFs on gene expression. Memory arises from time-scale separation among three circuit’s constituent processes: basal erasure, auto and cross-catalysis, and recruited erasure of modifications. When the two latter processes are sufficiently faster than the former, the circuit exhibits bistability and hysteresis, allowing active and repressed gene states to coexist and persist after TF stimulus removal. The duration of memory is stochastic with a mean value that increases as time-scale separation increases, but more so for the repressed state. This asymmetry stems from the cross-catalysis between repressive histone modifications and DNA methylation and is enhanced by the relatively slower decay rate of the latter. Nevertheless, TF-mediated positive autoregulation can rebalance this asymmetry and even confers robustness of active states to repressive stimuli. More generally, by wiring positively autoregulated chromatin modification circuits under time scale separation, long-term distinct gene expression patterns arise, which are also robust to failure in the regulatory links.
Splicing inactivation generates hybrid mRNA-snoRNA transcripts targeted by cytoplasmic RNA decay
Authors: Liu Yanru , DeMario Samuel , He Kevin , Gibbs Michelle R. , Barr Keaton W. , Chanfreau Guillaume F. 
Published: February 2022

AbstractMany small nucleolar RNAs (snoRNA)s are processed from introns of host genes, but the importance of splicing for proper biogenesis and the fate of the snoRNAs is not well understood. Here we show that inactivation of splicing factors or mutation of splicing signals leads to the accumulation of partially processed hybrid mRNA-snoRNA transcripts (hmsnoRNA). HmsnoRNAs are processed to the mature 3′-ends of the snoRNAs by the nuclear exosome and bound by snoRNP proteins. HmsnoRNAs are unaffected by translation-coupled RNA quality control pathways, but they are degraded by the major cytoplasmic exonuclease Xrn1p due to their mRNA-like 5′-extensions. These results show that completion of splicing is required to promote complete and accurate processing of intron-encoded snoRNAs and that splicing defects lead to degradation of hybrid mRNA-snoRNA species by cytoplasmic decay, underscoring the importance of splicing for the biogenesis of intron encoded snoRNAs.Significance StatementSmall nucleolar RNAs mediate modifications of nucleosides within ribosomal RNAs, which are necessary for proper ribosomal function and translation. Many snoRNAs are encoded within introns of host genes and accurate biogenesis of these small RNAs is required to produce functional snoRNAs. The work presented here shows that when the splicing reactions are inactivated, snoRNAs undergo a distinct biogenesis pathway which leads to the production of aberrant hybrid RNAs that contain both mRNAs and small RNAs components of the host genes. While snoRNAs are primarily found in the nucleolus, these hybrid RNAs are degraded by the cytoplasmic mRNA degradation pathway. These results demonstrate the importance of splicing to promote accurate snoRNA processing and prevent the production of aberrant mRNA-snoRNA hybrids.
Machine Learning and Radiomics for Osteoporosis Risk Prediction Using X-ray Imaging
Authors: Dadsetan Saba , Kitamura Gene , Arefan Dooman , Guo Yuan , Clancy Kadie , Yang Lu , Wu Shandong 
Published: February 2022

AbstractOsteoporosis is a significant health and economic issue, as it predisposes patients to a higher risk of bone fracture. Measuring bone mineral density has been shown to be an accurate way to assess the risk for osteoporosis. The most common way for bone density testing is a dual-energy X-ray absorptiometry (DEXA) scan, which may be recommended for patients with increased risk of osteoporosis. Radiograph imaging is widely available in clinical settings and acquired for many reasons, such as trauma or pain. The goal of this project is to extract radiomics information from pelvic X-rays (both the hip and femoral neck regions) to assess the risk of osteoporosis (triaging patients into “normal” vs. “at-risk”, or “low risk” vs. “high risk” categories). The motivation here is not to replace the DEXA scan but to proactively identify patients at risk for osteoporosis and appropriately refer them to management options. We apply machine learning-based radiomics techniques on a study cohort of 565 patients. Our preliminary results show that a correlation between the radiomics features extracted from pelvic X-rays and the level of osteoporosis risk derived from the DEXA test results.
Comprehensive comparison between azacytidine and decitabine treatment in an acute myeloid leukemia cell line
Authors: Aumer Tina , Gremmelmaier Constanze B. , Runtsch Leander S. , Yeşiltaç Nur , Kaiser Stefanie , Traube Franziska R. 
Published: February 2022

AbstractAzacytidine (AzaC) and decitabine (AzadC) are cytosine analogs that covalently trap DNA methyltransferases, which place the important epigenetic mark 5-methyl-2’-deoxycytidine by methylating 2’-deoxycytidine (dC) at the C5 position. AzaC and AzadC are used in the clinic as antimetabolites to treat myelodysplastic syndrome and acute myeloid leukemia and are explored against other types of cancer. Although their principal mechanism of action is known, the downstream effects of AzaC and AzadC treatment are not well understood and the cellular prerequisites that determine sensitivity towards AzaC and AzadC remain elusive. Here, we investigated the effects and phenotype of AzaC and AzadC exposure on the acute myeloid leukemia cell line MOLM-13. We found that while AzaC and AzadC share many effects on the cellular level, including decreased global DNA methylation, increased formation of DNA double strand breaks, transcriptional downregulation of important oncogenes and similar changes on the proteome level, AzaC failed in contrast to AzadC to induce apoptosis in MOLM-13. The only cellular marker that correlated with this clear phenotypical outcome was the level of hydroxy-methyl-dC, an additional epigenetic mark that is placed by TET enzymes and repressed in cancer cells. Whereas AzadC increased hmdC substantially in MOLM-13, AzaC treatment did not result in any increase at all. This suggests that hmdC levels in cancer cells should be monitored as a response towards AzaC and AzadC and considered as a biomarker to judge whether AzaC or AzadC treatment leads to cell death in leukemic cells.
Activating ligands of Uncoupling protein 1 identified by rapid membrane protein thermostability shift analysis
Authors: Cavalieri Riccardo , Hazebroek Marlou Klein , Cotrim Camila A. , Lee Yang , Kunji Edmund R. S. , Jastroch Martin , Keipert Susanne , Crichton Paul G. 
Published: February 2022

AbstractUncoupling protein 1 (UCP1) catalyzes mitochondrial proton leak in brown adipose tissue for heat production, and may combat metabolic disease if activated in humans. During the adrenergic stimulation of brown adipocytes, free fatty acids generated from lipolysis activate UCP1 via an unclear interaction. Here, we have utilized membrane protein thermostability shift analysis to characterize the interaction of activating molecules with purified UCP1. We reveal that activators influence the protein through a specific destabilizing interaction, behaving as transport substrates that shift UCP1 to a less stable conformation of a transport cycle. Through the detection of specific stability shifts in screens, we identify novel activators, including the drug ibuprofen, where ligand analysis indicates a relatively wide structural specificity for interacting molecules. Ibuprofen induces UCP1 activity in liposomes and isolated brown fat mitochondria, but not in cultured brown adipocytes. Though the drug does induce activity in UCP1-expressing HEK293 cells, demonstrating that the targeting of UCP1 in cells by approved drugs is in principle achievable as a therapeutic avenue, but requires variants with more effective delivery in brown adipocytes.
Exploring the lncRNA localization landscape within the retinal pigment epithelium under normal and stress conditions
Authors: Kaczynski Tadeusz J. , Au Elizabeth D. , Farkas Michael H. 
Published: February 2022

AbstractLong noncoding RNAs (lncRNAs) are emerging as a class of genes whose importance has yet to be fully realized. It is becoming clear that the primary function of lncRNAs is to regulate gene expression, and they do so through a variety of mechanisms that are critically tied to their subcellular localization. Although most lncRNAs are poorly understood, mapping lncRNA subcellular localization can provide a foundation for understanding these mechanisms. Here, we present an initial step toward uncovering the localization landscape of lncRNAs in the human retinal pigmented epithelium (RPE) using high throughput RNA-Sequencing (RNA-Seq). To do this, we differentiated human induced pluripotent stem cells (iPSCs) into RPE, isolated RNA from nuclear and cytoplasmic fractions, and performed RNA-Seq on both. Furthermore, we investigated lncRNA localization changes that occur in response to oxidative stress. We discovered that, under normal conditions, most lncRNAs (76%) are seen in both the nucleus and the cytoplasm to a similar degree, but of the transcripts that are highly enriched in one compartment, more are nuclear (18.6%) than cytoplasmic (5.6%). Interestingly, under oxidative stress conditions, we observed an increase in lncRNA localization in both nuclear (23.5%) and cytoplasmic (9.7%) fractions. In addition, we found that nuclear localization was partially attributable to the presence of previously described nuclear retention motifs, while adenosine to inosine (A-to-I) RNA editing appeared to play a very minimal role. Our findings regarding lncRNA localization in the RPE provide two avenues for future research: 1) how lncRNAs function in the RPE, and 2) how one environmental factor, in isolation, may play a role in retinal disease pathogenesis.
Identification of putative enhancer-like elements predicts regulatory networks active in planarian adult stem cells
Authors: Neiro Jakke , Sridhar Divya , Dattani Anish , Aboobaker Aziz 
Published: February 2022

AbstractPlanarians have become an established model system to study regeneration and stem cells, but the regulatory elements in the genome remain almost entirely undescribed. Here, by integrating epigenetic and expression data we use multiple sources of evidence to predict enhancer elements active in the adult stem cell populations that drive regeneration. We have used ChIP-seq data to identify regions with histone modifications consistent with enhancer identity and activity, and ATAC-seq data to identify accessible chromatin. Overlapping these signals allowed for the identification of a set of high confidence candidate enhancers predicted to be active in planarian adult stem cells. These enhancers are enriched for predicted transcription factor (TF) binding sites for TFs and TF families expressed in planarian adult stem cells. Foot-printing analyses provided further evidence that these potential TF binding sites are potentially occupied in adult stem cells. We integrated these analyses to build testable hypotheses for the regulatory function of transcription factors in stem cells, both with respect to how pluripotency might be regulated, and to how lineage differentiation programs are controlled. We found that our predicted GRNs were independently supported by existing TF RNAi/RNA-seq data sets, providing further evidence that our work predicts active enhancers regulating adult stem cells and regenerative mechanisms.