bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of different surgical techniques and displacement distances on the soft tissue profile via orthodontic-orthognathic treatment of class II and class III malocclusions
Authors: Möhlhenrich Stephan Christian , Kötter Florian , Peters Florian , Kniha Kristian , Chhatwani Sachin , Danesh Gholamreza , Hölzle Frank , Modabber Ali 
Published: April 2021

AbstractBackgroundOrthognathic surgery can be carried out using isolated mandibular or maxillary movement and bimaxillary procedures. In cases of moderate skeletal malocclusion, camouflage treatment by premolar extraction is another treatment option. All these surgical procedures can have a different impact on the soft tissue profile.MethodsThe changes in the soft tissue profile of 187 patients (Class II: 53, Class III: 134) were investigated. The treatment approaches were differentiated as follows: Class II: mandible advancement (MnA), bimaxillary surgery (MxS/MnA), upper extraction (UpEX), or Class III: maxillary advancement (MxA), mandible setback (MnS), bimaxillary surgery (MxA/MnS), and lower extraction (LowEX) as well as the extent of skeletal deviation (moderate Wits appraisal: − 7 mm to 7 mm, pronounced: Wits <− 7 mm, > 7 mm, respectively). This resulted in five groups for Class II treatment and seven groups for Class III treatment.ResultsIn the Class II patients, a statistically significant difference (p ≤ 0.05) between UpEX and moderate MnA was found for facial profile (N′-Prn-Pog’), soft tissue profile (N′-Sn-Pog’), and mentolabial angle (Pog’-B′-Li). In the Class III patients, a statistically significant differences (p ≤ 0.05) occurred between LowEX and moderate MxA for facial profile (N′-Prn-Pog’), soft tissue profile (N′-Sn-Pog’), upper and lower lip distacne to esthetic line (Ls/Li-E-line), and lower lip length (Sto-Gn’). Only isolated significant differences (p < 0.05) were recognized between the moderate surgical Class II and III treatments as well between the pronounced Class III surgeries. No statistical differences were noticed between moderate and pronounced orthognathic surgery.ConclusionsWhen surgery is required, the influence of orthognathic surgical techniques on the profile seems to be less significant. However, it must be carefully considered if orthognathic or camouflage treatment should be done in moderate malocclusions as a moderate mandibular advancement in Class II therapy will straighten the soft tissue profile much more by increasing the facial and soft tissue profile angle and reducing the mentolabial angle than camouflage treatment. In contrast, moderate maxillary advancement in Class III therapy led to a significantly more convex facial and soft tissue profile by decreasing distances of the lips to the E-Line as well as the lower lip length.
Identification of key regulators responsible for dysregulated networks in osteoarthritis by large-scale expression analysis
Authors: Shi Song , Wan Fuyin , Zhou Zhenyu , Tao Ran , Lu Yue , Zhou Ming , Liu Fan , Liu Yake 
Published: April 2021

Abstract
Background
Osteoarthritis (OA) is a worldwide musculoskeletal disorder. However, disease-modifying therapies for OA are not available. Here, we aimed to characterize the molecular signatures of OA and to identify novel therapeutic targets and strategies to improve the treatment of OA.

Methods
We collected genome-wide transcriptome data performed on 132 OA and 74 normal human cartilage or synovium tissues from 7 independent datasets. Differential gene expression analysis and functional enrichment were performed to identify genes and pathways that were dysregulated in OA. The computational drug repurposing method was used to uncover drugs that could be repurposed to treat OA.

Results
We identified several pathways associated with the development of OA, such as extracellular matrix organization, inflammation, bone development, and ossification. By protein-protein interaction (PPI) network analysis, we prioritized several hub genes, such as JUN, CDKN1A, VEGFA, and FOXO3. Moreover, we repurposed several FDA-approved drugs, such as cardiac glycosides, that could be used in the treatment of OA.

Conclusions
We proposed that the hub genes we identified would play a role in cartilage homeostasis and could be important diagnostic and therapeutic targets. Drugs such as cardiac glycosides provided new possibilities for the treatment of OA.
A ZFYVE19 gene mutation associated with neonatal cholestasis and cilia dysfunction: case report with a novel pathogenic variant
Authors: Mandato Claudia , Siano Maria Anna , Nazzaro Lucia , Gelzo Monica , Francalanci Paola , Rizzo Francesca , D’Agostino Ylenia , Morleo Manuela , Brillante Simona , Weisz Alessandro , Franco Brunella , Vajro Pietro 
Published: April 2021

Abstract
Background
ZFYVE19 (Zinc Finger FYVE-Type Containing 19) mutations have most recently been associated to a novel type of high gamma-glutamyl transpeptidase (GGT), non-syndromic, neonatal-onset intrahepatic chronic cholestasis possibly associated to cilia dysfunction. Herein, we report a new case with further studies of whole exome sequencing (WES) and immunofluorescence in primary cilia of her cultured fibroblasts which confirm the observation.

Results
A now 5-year-old girl born to clinically healthy consanguineous Moroccan parents was assessed at 59 days of life due to severe cholestatic jaundice with increased serum bile acids and GGT, and preserved hepatocellular synthetic function. Despite fibrosis/cirrhosis and biliary ducts proliferation on liver biopsy suggested an extrahepatic biliary obstacle, normal intra-operatory cholangiography excluded biliary atresia. Under choleretic treatment, she maintained a clinically stable anicteric cholestasis but developped hyperlipidemia. After exclusion of the main causes of cholestasis by multiple tests, abnormal concentrations of sterols and WES led to a diagnosis of hereditary sitosterolemia (OMIM #618666), likely unrelated to her cholestasis. Further sequencing investigation revealed a homozygous non-sense mutation (p.Arg223Ter) in ZFYVE19 leading to a 222 aa truncated protein and present in both heterozygous parents. Immunofluorescence analysis of primary cilia on cultured skin fibroblasts showed a ciliary phenotype mainly defined by fragmented cilia and centrioles abnormalities.

Conclusions
Our findings are consistent with and expands the recent evidence linking ZFYVE19 to a novel, likely non-syndromic, high GGT-PFIC phenotype with neonatal onset. Due to the possible role of ZFYVE19 in cilia function and the unprecedented coexistence of a coincidental hereditary sterol disorder in our case, continuous monitoring will be necessary to substantiate type of liver disease progression and/or possible emergence of a multisystemic involvement. What mentioned above confirms that the application of WES in children with undiagnosed cholestasis may lead to the identification of new causative genes, widening the knowledge on the pathophysiology.
AIF3 splicing switch triggers neurodegeneration
Authors: Liu Shuiqiao , Zhou Mi , Ruan Zhi , Wang Yanan , Chang Calvin , Sasaki Masayuki , Rajaram Veena , Lemoff Andrew , Nambiar Kalyani , Wang Jennifer E. , Hatanpaa Kimmo J. , Luo Weibo , Dawson Ted M. , Dawson Valina L. , Wang Yingfei 
Published: April 2021

Abstract
Background
Apoptosis-inducing factor (AIF), as a mitochondrial flavoprotein, plays a fundamental role in mitochondrial bioenergetics that is critical for cell survival and also mediates caspase-independent cell death once it is released from mitochondria and translocated to the nucleus under ischemic stroke or neurodegenerative diseases. Although alternative splicing regulation of AIF has been implicated, it remains unknown which AIF splicing isoform will be induced under pathological conditions and how it impacts mitochondrial functions and neurodegeneration in adult brain.

Methods
AIF splicing induction in brain was determined by multiple approaches including 5′ RACE, Sanger sequencing, splicing-specific PCR assay and bottom-up proteomic analysis. The role of AIF splicing in mitochondria and neurodegeneration was determined by its biochemical properties, cell death analysis, morphological and functional alterations and animal behavior. Three animal models, including loss-of-function harlequin model, gain-of-function AIF3 knockin model and conditional inducible AIF splicing model established using either Cre-loxp recombination or CRISPR/Cas9 techniques, were applied to explore underlying mechanisms of AIF splicing-induced neurodegeneration.

Results
We identified a nature splicing AIF isoform lacking exons 2 and 3 named as AIF3. AIF3 was undetectable under physiological conditions but its expression was increased in mouse and human postmortem brain after stroke. AIF3 splicing in mouse brain caused enlarged ventricles and severe neurodegeneration in the forebrain regions. These AIF3 splicing mice died 2–4 months after birth. AIF3 splicing-triggered neurodegeneration involves both mitochondrial dysfunction and AIF3 nuclear translocation. We showed that AIF3 inhibited NADH oxidase activity, ATP production, oxygen consumption, and mitochondrial biogenesis. In addition, expression of AIF3 significantly increased chromatin condensation and nuclear shrinkage leading to neuronal cell death. However, loss-of-AIF alone in harlequin or gain-of-AIF3 alone in AIF3 knockin mice did not cause robust neurodegeneration as that observed in AIF3 splicing mice.

Conclusions
We identified AIF3 as a disease-inducible isoform and established AIF3 splicing mouse model. The molecular mechanism underlying AIF3 splicing-induced neurodegeneration involves mitochondrial dysfunction and AIF3 nuclear translocation resulting from the synergistic effect of loss-of-AIF and gain-of-AIF3. Our study provides a valuable tool to understand the role of AIF3 splicing in brain and a potential therapeutic target to prevent/delay the progress of neurodegenerative diseases.
Knowledge, attitude, practice and associated factors of health professionals towards podoconiosis in Gamo zone, Ethiopia, 2019
Authors: Churko Chuchu , Asnakew Asfaw Mekuria , Tunje Abayneh , Girma Eyayou , Zerdo Zerihun 
Published: April 2021

AbstractBackgroundPodoconiosis is entirely preventable, non‐communicable disease with high potential of elimination. The prevalence of podoconiosis in Ethiopia was 7.45%. One of the pillars for elimination of podoconiosis is morbidity control and management. Therefore, the present study aimed to assess the knowledge, attitude, practices and associated factors of health professionals towards podoconiosis cause, prevention and treatments.MethodsFacility based cross‐sectional study was conducted. The source population was all health professionals currently working in public health facilities. The final estimated sample size was 349. A pretested self‐administrated structured questionnaire was used to collect the data. The data were coded, entered, and cleaned by using Epi.info version7, and analyzed by using SPSS version 20.ResultA total of 320 health professionals participated in the study. Sixty eight (23.1%) health professionals had poor knowledge towards podoconiosis. Seventy (21.9%) identified podoconiosis as infectious disease. Profession, address of health facility, service year and attitude of participants were significantly associated with knowledge towards podoconiosis. More than half (56%) had favorable attitude towards podoconiosis patients. Knowledge score (95%CI: 1.389, 4.059, p‐value = 0.002) was the independent predictor for attitude status. Very few (11.6%) respondents treated podoconiosis patients. Age group 45 years old and above and training on lymphedema morbidity management and disability prevention were significantly associated with clinical experience in treating affected patients, (AOR = 17.345; 95%CI: 4.62, 65.119) and (AOR = 7.385; 95%CI: 2.5, 21.797), respectively.ConclusionDespite, high percent of good knowledge of health professionals towards podoconiosis, clinical experience of health professionals in treating podoconiosis patients was very low. In‐service trainings will be given for health professionals to improve treatment. In podoconiosis endemic districts hygiene supplies and other referencing materials should be made available for podoconiosis case management.
Conducting clinical trials during the COVID-19 pandemic—a collaborative trial network response
Authors:   on behalf of the Australasian Kidney Trials Network, Robison Laura , Cho Yeoungjee , Viecelli Andrea K. , Johnson David W. , Hawley Carmel M. , Valks Andrea , Paul-Brent Peta-Anne , Stastny Ruth , Varghese Julie , Kiriwandeniya Charani , Pascoe Elaine M. , Vergara Liza A. , Fahim Magid A. , Boudville Neil , Krishnasamy Rathika , Reidlinger Donna 
Published: April 2021

AbstractThe unprecedented demand placed on healthcare systems from the COVID-19 pandemic has forced a reassessment of clinical trial conduct and feasibility. Consequently, the Australasian Kidney Trials Network (AKTN), an established collaborative research group known for conducting investigator-initiated global clinical trials, had to efficiently respond and adapt to the changing landscape during COVID-19. Key priorities included ensuring patient and staff safety, trial integrity and network sustainability for the kidney care community. New resources have been developed to enable a structured review and contingency plan of trial activities during the pandemic and beyond.
Efficiency of atorvastatin on in-hospital mortality of patients with acute aortic dissection (AAD): study protocol for a randomized, open-label, superiority clinical trial
Authors: Chen Yequn , Xiong Nianling , Wang Xin , Wu Shiwan , Hong Liangli , Huang Xiru , Chen Chang , Li Weiping , Wang Bin , Ye Shu , Tan Xuerui 
Published: April 2021

Abstract
Background
Dyslipidemia and local inflammation at sites of lipid deposition on blood vessel walls have been demonstrated to be risk factors for patients with acute aortic dissection (AAD). Statins have anti-inflammatory and lipid-lowering effects, which suggest that statins may play an important role in the prevention and treatment of AAD. Some retrospective studies show that statins can protect patients with aortic dissection. However, the effect of statins on the survival of AAD patients has been scarcely investigated, especially in randomized trials. In this study, we will perform a randomized clinical trial to understand whether statins can reduce in-hospital mortality of AAD patients.

Methods
A total of 384 subjects diagnosed with AAD in the First Affiliated Hospital of Shantou University Medical College will be recruited. Participants will be randomly divided into an atorvastatin-treated or control group. The primary outcome will be the in-hospital mortality at 30 days.

Discussion
This study is designed to verify the efficacy of atorvastatin on reducing in-hospital mortality of patients with AAD. The aim is to provide a new means of improving survival as a complement to conventional drug therapy.

Trial registration
Chinese Clinical Trials Registry ChiCTR1900023515. Registered on 1 June 2019.
Evaluation using latent class models of the diagnostic performances of three ELISA tests commercialized for the serological diagnosis of Coxiella burnetii infection in domestic ruminants
Authors: Lurier Thibaut , Rousset Elodie , Gasqui Patrick , Sala Carole , Claustre Clément , Abrial David , Dufour Philippe , de Crémoux Renée , Gache Kristel , Delignette-Muller Marie Laure , Ayral Florence , Jourdain Elsa 
Published: April 2021

AbstractELISA methods are the diagnostic tools recommended for the serological diagnosis of Coxiella burnetii infection in ruminants but their respective diagnostic performances are difficult to assess because of the absence of a gold standard. This study focused on three commercial ELISA tests with the following objectives (1) assess their sensitivity and specificity in sheep, goats and cattle, (2) assess the between- and within-herd seroprevalence distribution in these species, accounting for diagnostic errors, and (3) estimate optimal sample sizes considering sensitivity and specificity at herd level. We comparatively tested 1413 cattle, 1474 goat and 1432 sheep serum samples collected in France. We analyzed the cross-classified test results with a hierarchical zero-inflated beta-binomial latent class model considering each herd as a population and conditional dependence as a fixed effect. Potential biases and coverage probabilities of the model were assessed by simulation. Conditional dependence for truly seropositive animals was high in all species for two of the three ELISA methods. Specificity estimates were high, ranging from 94.8% [92.1; 97.8] to 99.2% [98.5; 99.7], whereas sensitivity estimates were generally low, ranging from 39.3 [30.7; 47.0] to 90.5% [83.3; 93.8]. Between- and within-herd seroprevalence estimates varied greatly among geographic areas and herds. Overall, goats showed higher within-herd seroprevalence levels than sheep and cattle. The optimal sample size maximizing both herd sensitivity and herd specificity varied from 3 to at least 20 animals depending on the test and ruminant species. This study provides better interpretation of three widely used commercial ELISA tests and will make it possible to optimize their implementation in future studies. The methodology developed may likewise be applied to other human or animal diseases.
Mapping evidence on ovarian, endometrial, vaginal, and vulva cancer research in Africa: a scoping review protocol
Authors: Ninimiya Sebastian Yidana , Ansu-Mensah Monica , Bawontuo Vitalis , Kuupiel Desmond 
Published: April 2021

AbstractBackgroundGlobally, cancer is generally recognized as a developmental threat yet most countries in Africa lack capacity to diagnose cancer especially gynecological cancers resulting in late detection and poor outcomes. However, most studies on gynecological cancers in Africa tend to focus on cervical cancer compared to the other gynecological cancers. Therefore, this scoping review will aim to describe the existing literature on the epidemiological burden of ovarian, endometrial, vaginal, and vulva cancers, their risk factors, and potential screening methods/techniques in Africa to identify priority research gaps for further research to inform health policy decisions.MethodsThe framework promulgated by Arksey and O’Malley and improved by Levac et al. will be used as a guide for this scoping review. A comprehensive search for relevant published studies in PubMed, CINAHL, SCOPUS, Google Scholar, and ScienceDirect with no date limitation to the last search date. The database search strategy will include keywords, Boolean operators, and medical subject heading terms. We will additionally consult the WHO/IARC website, IHME/Global Burden of Disease Study. A snowball approach will also be used to search the reference list of all included studies to obtain relevant papers for possible inclusion in this review. We will include articles that involve African countries, focused on ovarian, endometrial, vaginal, and vulva cancers, their risk factors, and potential screening methods/techniques in any language. We will exclude studies on cervical cancer and other cancers as well as review articles. The abstracts and full-text selection will be conducted by two independent reviewers using this review’s eligibility criteria as a guide. All the review selection tools, and the data extraction form will be pilot tested for accuracy and consistency. The data will be organized into thematic areas, summarized and the results communicated narratively.DiscussionIt is anticipated that this review will reveal important literature gaps to guide future research to inform health policy decisions about ovarian, endometrial, and rare gynecological neoplasms in Africa. This review’s findings will be disseminated via peer review journals, conferences, and other social media such Twitter and LinkedIn.
Human alpha-synuclein overexpressing MBP29 mice mimic functional and structural hallmarks of the cerebellar subtype of multiple system atrophy
Authors: Mészáros Lisa , Riemenschneider Markus J. , Gassner Heiko , Marxreiter Franz , von Hörsten Stephan , Hoffmann Alana , Winkler Jürgen 
Published: April 2021

AbstractMultiple system atrophy (MSA) is a rare, but fatal atypical parkinsonian disorder. The prototypical pathological hallmark are oligodendroglial cytoplasmic inclusions (GCIs) containing alpha-synuclein (α-syn). Currently, two MSA phenotypes are classified: the parkinsonian (MSA-P) and the cerebellar subtype (MSA-C), clinically characterized by predominant parkinsonism or cerebellar ataxia, respectively. Previous studies have shown that the transgenic MSA mouse model overexpressing human α-syn controlled by the oligodendroglial myelin basic protein (MBP) promoter (MBP29-hα-syn mice) mirrors crucial characteristics of the MSA-P subtype. However, it remains elusive, whether this model recapitulates important features of the MSA-C-related phenotype. First, we examined MSA-C-associated cerebellar pathology using human post-mortem tissue of MSA-C patients and controls. We observed the prototypical GCI pathology and a preserved number of oligodendrocytes in the cerebellar white matter (cbw) accompanied by severe myelin deficit, microgliosis, and a profound loss of Purkinje cells. Secondly, we phenotypically characterized MBP29-hα-syn mice using a dual approach: structural analysis of the hindbrain and functional assessment of gait. Matching the neuropathological features of MSA-C, GCI pathology within the cbw of MBP29-hα-syn mice was accompanied by a severe myelin deficit despite an increased number of oligodendrocytes and a high number of myeloid cells even at an early disease stage. Intriguingly, MBP29-hα-syn mice developed a significant loss of Purkinje cells at a more advanced disease stage. Catwalk XT gait analysis revealed decreased walking speed, increased stride length and width between hind paws. In addition, less dual diagonal support was observed toward more dual lateral and three paw support. Taken together, this wide-based and unsteady gait reflects cerebellar ataxia presumably linked to the cerebellar pathology in MBP29-hα-syn mice. In conclusion, the present study strongly supports the notion that the MBP29-hα-syn mouse model mimics important characteristics of the MSA-C subtype providing a powerful preclinical tool for evaluating future interventional strategies.
Spatial scale of geomagnetic Pc5/Pi3 pulsations as a factor of their efficiency in generation of geomagnetically induced currents
Authors: Yagova Nadezda V , Pilipenko Vyacheslav A , Sakharov Yaroslav A , Selivanov Vasily N 
Published: April 2021

AbstractGeomagnetically induced currents (GICs) in a quasi-meridional power transmission line on the Kola Peninsula are analyzed during the intervals of Pc5/Pi3 (frequency range from 1.5 to 5 mHz) pulsations recorded at the IMAGE magnetometer network. We have analyzed GIC in a transformer at the terminal station Vykhodnoy ($$68^{\circ }$$68∘ N,$$33^{\circ }$$33∘ E) during the entire year of 2015, near the maximum of the 24th Solar cycle. To quantify the efficiency of GIC generation by geomagnetic pulsations, a ratio between power spectral densities of GIC and magnetic field variations is introduced. Upon examination of the geomagnetic pulsation efficiency in GIC generation, the emphasis is given to its dependence on frequency and spatial scale. To estimate pulsation spatial scales in latitudinal and longitudinal directions, the triangle of stations KEV-SOD-KIL has been used. Large-scale pulsations (with a high spectral coherence, low phase difference, and similar amplitudes at latitudinally separated stations) are found to be more effective in GIC generation than small-scale pulsations. The GIC response also depends on the pulsation scale across the electric power line.