bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-206 improves intervertebral disk degeneration by targeting GJA1
Authors: Zhou Peng , Xu Peng , Yu Wantao , Li Huan 
Published: March 2022

Abstract
Background
A large amount of evidence suggested that miRNA was involved in the progression of intervertebral disk degeneration (IDD). The purpose of our study was to explore the function and potential mechanism of miR-206/GJA1 axis in IDD.

Methods
IDD nucleus pulposus (NP) cell model was established through treatment of LPS. IDD rat model was established by annulus fibrosus puncture. The expression of miR-206 and GJA1 was detected by RT-PCR, apoptosis was evaluated by flow cytometry or TUNEL, inflammatory factors were tested by ELISA, extracellular matrix related protein expression was detected by western blot, and HE and safranin-O staining were used to assess the pathological changes of IDD.

Results
GJA1 was found to be highly expressed in IDD tissues and LPS-induced NP cells. Down regulation of GJA1 reduced inflammatory factors, inhibited apoptosis and enhanced extracellular matrix in LPS-induced NP cells. MiR-206 was downregulated in IDD tissues and directly targeted GJA1, and the expression of miR-206 was negatively correlated with the expression of GJA1 in IDD tissues. Further, it was demonstrated that overexpression of miR-206 could attenuate LPS-induced NP cell injury by targeting GJA1. In vivo, the upregulation of miR-206 improved IDD and reduced NP cell apoptosis.

Conclusion
Our study showed that miR-206 reduced the level of inflammatory factors, restrained NP cell apoptosis and increases extracellular matrix by targeting GJA1. These data suggested that miR-206/GJA1 might be potential therapeutic targets for IDD.
Central acetabular osteophytes (CAO) are more prevalent in the borderline developmental dysplastic hip (BDDH) patients: a propensity-score matched CT study
Authors: Yang Fan , Huang Hong-Jie , He Zi-Yi , Xu Yan , Zhang Xin , Wang Jian-Quan 
Published: March 2022

Abstract
Background
The acetabular fossa often showing the first signs of degeneration, Central acetabular osteophytes (CAO) have been increasingly recognized during hip arthroscopy. The purpose of this study was to investigate the condition of CAO in BDDH hips and compare cotyloid fossa size between the BDDH and the non-BDDH hips on CT images.

Methods
We performed a retrospective analysis of prospectively collected data of hip CT images of FAI or labral injury patients. A 1:2 propensity-score matched observational study comparing the linear length of cotyloid fossa was analyzed. Cotyloid fossa width (CFW) and cotyloid notch width (CNW) were measured on axial images, cotyloid fossa height (CFH) and cotyloid fossa depth (CFD) were measured on coronal images. Within the CAO patients, we performed central acetabular decompression (CAD) and then observed the morphology change in fossa.

Results
Propensity-score matching yielded 61 BDDH hips and 122 non-BDDH hips. BDDH hips had a higher prevalence of CAO and a decreased linear length of cotyloid fossa (CFW, CFH and CNW). In the BDDH group, 33 hips underwent CAD, postoperative CFW, CFH and CNW were significantly increased (p < .001 for all), and had no statistical difference compared with the non-BDDH hips (p = .193, p = .132, p = .421, respectively).

Conclusion
BDDH hips had a significantly higher prevalence of CAO than adequate acetabular coverage hips. After the procedure of CAD, BDDH hips were found to have acetabular parameters (CFW, CFH, CNW) and were restored to that of the control hips.
Efficacy of direct anterior approach combined with direct posterior approach in Pipkin IV femoral head fractures
Authors: Liu Bo , Zhao Binghao , Zhang Qingsong 
Published: March 2022

Abstract
Objective
The study aimed to explore the efficacy of direct anterior approach combined with direct posterior approach in Pipkin IV femoral head fractures.

Methods
The study enrolled 64 patients with Pipkin IV femoral head fractures who were treated at our hospital between March 2019 and April 2020. They were assigned to the control group and the study group using the random number table method with 32 patients in each group and received treatment by the direct anterior approach and treatment by the direct anterior approach combined with the direct posterior approach. The operative time, intraoperative estimated blood loss, postoperative drainage time, drainage volume, time to partial and full weight-bearing, total length of hospital stay and the levels of hemoglobin (Hb) and hematocrit (Hct) in the two groups were compared, and severity of pain and hip function at different time points postoperatively were observed, and the occurrences of complications were compared.

Results
There was no statistical difference in the operative time and intraoperative estimated blood loss between the two groups (P > 0.05). Compared with the control group, the study group had shorter postoperative drainage time, lower drainage volume, shorter time to partial and full weight-bearing, and shorter total length of hospital stay, and the difference was statistically different (P < 0.05). There was no significant difference in Hb and Hct levels between the two groups before surgery (P > 0.05). The levels of Hb and Hct in both groups at postoperative day (POD) 1 were lower than those before surgery, and the levels of Hb and Hct in the study group were significantly higher than those in the control group (P < 0.05). Compared with the control group, the study group had significantly less severe pain at POD 1 and 7 and 1, 3 and 6 months postoperatively (P < 0.05). Compared with the control group, the study group had significantly better hip function at 3, 6 and 12 months postoperatively (P < 0.05). All patients were followed up for 12 months, and 1 case of ectopic ossification appeared in both groups 3 months postoperatively, both Brooker grade I. No special treatment was provided as it did not interfere with the mobility of the hip and caused no apparent discomfort in the patients. In the current study, no incision infection, ischemic necrosis of the femoral head, breakage of the internal fixation device, fracture nonunion and loss of fracture reduction and other complications were reported in any patients.

Conclusion
Direct anterior approach combined with direct posterior approach in Pipkin IV femoral head fractures does not increase operative time and intraoperative estimated blood loss but can lessen severity of pain and promote functional recovery of the hip, leading to a favorable prognosis while not increasing the incidence of complications.
Loss of calsyntenin paralogs disrupts interneuron stability and mouse behavior
Authors: Mori Keita , Koebis Michinori , Nakao Kazuki , Kobayashi Shizuka , Kiyama Yuji , Watanabe Masahiko , Manabe Toshiya , Iino Yuichi , Aiba Atsu 
Published: March 2022

AbstractCalsyntenins (CLSTNs) are important synaptic molecules whose molecular functions are not fully understood. Although mutations in calsyntenin (CLSTN) genes have been associated with psychiatric disorders in humans, their function is still unclear. One of the reasons why the function of CLSTNs in the nervous system has not been clarified is the functional redundancy among the three paralogs. Therefore, to investigate the functions of mammalian CLSTNs, we generated triple knockout (TKO) mice lacking all CLSTN paralogs and examined their behavior. The mutant mice tended to freeze in novel environments and exhibited hypersensitivity to stress. Consistent with this, glucose levels under stress were significantly higher in the mutant mice than in the wild-type controls. In particular, phenotypes such as decreased motivation, which had not been reported in single Clstn KO mice, were newly discovered. The TKO mice generated in this study represent an important mouse model for clarifying the function of CLSTN in the future.
Adverse stem cell clones within a single patient’s tumor predict clinical outcome in AML patients
Authors: Zeller Christina , Richter Daniel , Jurinovic Vindi , Valtierra-Gutiérrez Ilse A. , Jayavelu Ashok Kumar , Mann Matthias , Bagnoli Johannes W. , Hellmann Ines , Herold Tobias , Enard Wolfgang , Vick Binje , Jeremias Irmela 
Published: March 2022

AbstractAcute myeloid leukemia (AML) patients suffer dismal prognosis upon treatment resistance. To study functional heterogeneity of resistance, we generated serially transplantable patient-derived xenograft (PDX) models from one patient with AML and twelve clones thereof, each derived from a single stem cell, as proven by genetic barcoding. Transcriptome and exome sequencing segregated clones according to their origin from relapse one or two. Undetectable for sequencing, multiplex fluorochrome-guided competitive in vivo treatment trials identified a subset of relapse two clones as uniquely resistant to cytarabine treatment. Transcriptional and proteomic profiles obtained from resistant PDX clones and refractory AML patients defined a 16-gene score that was predictive of clinical outcome in a large independent patient cohort. Thus, we identified novel genes related to cytarabine resistance and provide proof of concept that intra-tumor heterogeneity reflects inter-tumor heterogeneity in AML.
Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth
Authors: Zamberlan Margherita , Boeckx Amandine , Muller Florian , Vinelli Federica , Ek Olivier , Vianello Caterina , Coart Emeline , Shibata Keitaro , Christian Aurélie , Grespi Francesca , Giacomello Marta , Struman Ingrid , Scorrano Luca , Herkenne Stéphanie 
Published: March 2022

Abstract
Background
Mitochondrial fusion and fission proteins have been nominated as druggable targets in cancer. Whether their inhibition is efficacious in triple negative breast cancer (TNBC) that almost invariably develops chemoresistance is unknown.

Methods
We used a combination of bioinformatics analyses of cancer genomic databases, genetic and pharmacological Optic Atrophy 1 (OPA1) inhibition, mitochondrial function and morphology measurements, micro-RNA (miRNA) profiling and formal epistatic analyses to address the role of OPA1 in TNBC proliferation, migration, and invasion in vitro and in vivo.

Results
We identified a signature of OPA1 upregulation in breast cancer that correlates with worse prognosis. Accordingly, OPA1 inhibition could reduce breast cancer cells proliferation, migration, and invasion in vitro and in vivo. Mechanistically, while OPA1 silencing did not reduce mitochondrial respiration, it increased levels of miRNAs of the 148/152 family known to inhibit tumor growth and invasiveness. Indeed, these miRNAs were epistatic to OPA1 in the regulation of TNBC cells growth and invasiveness.

Conclusions
Our data show that targeted inhibition of the mitochondrial fusion protein OPA1 curtails TNBC growth and nominate OPA1 as a druggable target in TNBC.
Re-creating reality: validation of fresh frozen full cadaver airway training with videolaryngoscopy and bougie FIRST strategy
Authors: Imach Sebastian , Kölbel Benny , Böhmer Andreas , Keipke Dorothee , Ahnert Tobias 
Published: March 2022

Abstract
Background
Tracheal intubation is the gold standard in emergency airway management. One way of measuring intubation quality is first pass success rate (FPSR). Mastery of tracheal intubation and maintenance of the skill is challenging for non-anesthesiologists. A combination of individual measures can increase FPSR. Videolaryngoscopy is an important tool augmenting laryngeal visualization. Bougie-first strategy can further improve FPSR in difficult airways. Standardized positioning maneuvers and manipulation of the soft tissues can enhance laryngeal visualization. Fresh frozen cadavers (FFC) are superior models compared to commercially manufactured manikins. By purposefully manipulating FFCs, it is possible to mimic the pre-hospital intubation conditions of helicopter emergency medical service (HEMS).

Methods
Twenty-four trauma surgeons (12 per Group, NOVICES: no pre-hospital experience, HEMS: HEMS physicians) completed an airway training course using FFCs. The FFCs were modified to match airway characteristics of 60 prospectively documented intubations by HEMS physicians prior to the study (BASELINE). In four scenarios the local HEMS airway standard (1: unaided direct laryngoscopy (DL), OLD) was compared to two scenarios with modifications of the intubation technique (2: augmented DL (bougie and patient positioning), 3: augmented videolaryngoscopy (aVL)) and a control scenario (4: VL and bougie, positioning by participant, CONTROL). FPSR, POGO score, Cormack and Lehane grade and duration of intubation were recorded. No participant had anesthesiological qualifications or experience in VL.

Results
The comparison between CONTROL and BASELINE revealed a significant increase of FPSR and achieved C&L grade for HEMS group (FPSR 100%, absolute difference 23%, p ≤ .001). The use of videolaryngoscopy, bougie, and the application of positioning techniques required significantly more time in the CONTROL scenario (HEMS group: mean 34.0 s (IQR 28.3–47.5), absolute difference to BASELINE: 13.0 s, p = .045). The groups differed significantly in the median number of real-life intubations performed in any setting (NOVICES n = 5 (IQR 0–18.75), HEMS n = 68 (IQR 37.25–99.75)). In the control scenario no significant differences were found between both groups. The airway characteristics of the FFC showed no significant differences compared to BASELINE.

Conclusion
Airway characteristics of a pre-hospital patient reference group cared for by HEMS were successfully reproduced in a fresh frozen cadaver model. In this setting, a combination of evidence based airway management techniques results in high FPSR and POGO rates of non-anesthesiological trained users. Comparable results (FPSR, POGO, duration of intubation) were achieved regardless of previous provider experience. The BOAH concept can therefore be used in the early stages of airway training and for skill maintenance.
Target temperature management following cardiac arrest: a systematic review and Bayesian meta-analysis
Authors: Aneman Anders , Frost Steven , Parr Michael , Skrifvars Markus B. 
Published: March 2022

AbstractBackgroundTemperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM.MethodsSystematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI).ResultsIn seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32–34 °C was 0.95 [95% CrI 0.78—1.09] for death and RR 0.93 [95% CrI 0.84—1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32–34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32–34 °C were the highest for an absolute risk reduction of 2–4% for death (28–53% chance) and unfavourable neurological outcome (63–78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%.ConclusionsThe posterior probability distributions did not support the use of TTM at 32–34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90–180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.
Caries inhibition with CO2-laser during orthodontic treatment: a study protocol for a randomized split-mouth controlled clinical trial
Authors: Belcheva Ani Bozhidarova , Shindova Maria Petrova 
Published: March 2022

Abstract
Introduction
White spot lesions associated with orthodontic treatment are a common problem. Recent studies reported increased resistance to acid demineralization of enamel after sub-ablative CO2-laser irradiation in a combination with fluoride application. The aim of the study is to assess the efficacy of CO2-laser in combination with a fluoride varnish in the prevention, severity, and extent of white spot lesions during orthodontic treatment with fixed appliances.

Methods and analysis
This is a protocol for a randomized, split-mouth controlled, clinical trial. The participants will be children aged 12–18 years at high caries risk, requiring fixed orthodontic treatment. The vestibular surfaces of maxillary anterior teeth of eligible patients will be exposed to CO2-laser irradiation in combination with fluoride therapy and fluoride therapy alone followed by bonding of orthodontic brackets. The patients will be recalled 6 and 12 months post-irradiation. Outcome measures will be visual examination with International Caries Detection and Assessment System criteria and SoproLife fluorescence. Data will be analyzed by Student’s t test for paired samples and proportional odds logistic regression model, p<0.05.

Ethics and dissemination
The study protocol has been approved by the Committee for Scientific Research Ethics, Medical University-Plovdiv, Bulgaria (Reference number P-605/27.03.2020, Protocol of approval No. 2/01.04.2021) and registered on a publicly accessible database. This research received institutional funding from the Medical University–Plovdiv, Bulgaria. The results will be presented through peer-reviewed publications and conference presentations.

Trial registration
ClinicalTrials.gov NCT04903275. Registered on June 2021.
Tolerance induction through early feeding to prevent food allergy in infants with eczema (TEFFA): rationale, study design, and methods of a randomized controlled trial
Authors: Kalb Birgit , Meixner Lara , Trendelenburg Valérie , Unterleider Nathalie , Dobbertin-Welsch Josefine , Heller Stephanie , Dölle-Bierke Sabine , Roll Stephanie , Lau Susanne , Lee Young-Ae , Fauchère Florent , Braun Julian , Babina Magda , Altrichter Sabine , Birkner Till , Worm Margitta , Beyer Kirsten 
Published: March 2022

Abstract
Background
Up to 8% of all children in industrialized countries suffer from food allergies, whereas children with atopic eczema are affected considerably more frequently. In addition, the type and starting time of weaning foods seem to influence the development of food allergies. However, data from interventional studies on weaning are controversial.
The aim of this randomized-controlled clinical trial is to investigate, whether an early introduction of hen's egg (HE), cow’s milk (CM), peanut (PN), and hazelnut (HN) in children with atopic eczema can reduce the risk for developing food allergies in the first year of life.

Methods
This is a protocol for a randomized, placebo controlled, double blind, single-center clinical trial.
One hundred fifty infants with atopic eczema at 4–8 months of age will be randomized in a 2:1 manner into an active group that will receive rusk-like biscuit powder with HE, CM, PN, and HN (initially approximately 2 mg of each food protein) for 6–8 months or a placebo group, whose participants will receive the same rusk-like biscuit powder without HE, CM, PN, and HN on a daily basis. During the interventional period, the amount of allergens in the study product will be increased three times, each after 6 weeks. All study participants who are sensitized to HE, CM, PN, or HN at the end of the interventional period will undergo an oral food challenge to the respective food in a further visit.
Primary endpoint is IgE-mediated food allergy to at least one of the four foods (HE, CM, PN or HN) after 6–8 months of intervention (i.e., at around 1 year of age). Secondary endpoints include multiple food allergies, severity of eczema, wheezing, and sensitization levels against food allergens.

Discussion
This clinical trial will assess whether an early introduction of allergenic foods into the diet of children with atopic eczema can prevent the development of food allergies. This trial will contribute to update food allergy prevention guidelines.

Trial registration
German Clinical Trials Register DRKS00016770. Registered on 09 January 2020.
Fluralaner 5.46% (w/w) flavored chewable tablet (Bravecto® 1-Month) is effective for treatment of canine generalized demodicosis
Authors: Rohdich Nadja , Meyer Leon , Guerino Frank 
Published: March 2022

AbstractBackgroundOrally administered fluralaner (13.64% w/w) is effective for treating canine generalized demodicosis. A study was initiated to assess the efficacy of a novel 5.46% w/w fluralaner chewable tablet formulation for monthly administration in the treatment of this disease.MethodsClient-owned dogs diagnosed with generalized demodicosis were acclimatized to laboratory conditions and randomized to receive either orally administered fluralaner (Bravecto®1-Month) (10.0 to 14.4 mg/kg body weight) (n = 8) or topical imidacloprid-moxidectin (Advocate®for dogs, Elanco) applied per label on days 0, 28, and 56 (n = 8), or more frequently for ongoing severe demodicosis. On days −2, 28, 56, and 84, deep skin scrapings were taken from five sites on each dog for mite identification and counting, and semiquantitative clinical assessments of generalized demodicosis were recorded. Primary efficacy was based upon arithmetic mean mite count reductions relative to pre-treatment.ResultsBy day 28, mean pre-treatment mite counts, > 600 in both groups, were significantly reduced by 99.7% and 89.5% (bothP < 0.001) in the fluralaner and imidacloprid-moxidectin groups, respectively. Parasitological cure (100% reduction in mite counts on days 56 and 84) was achieved in all fluralaner-treated dogs (100%) and in two imidacloprid-moxidectin-treated dogs (25%). In the imidacloprid-moxidectin group, the reduction in mean mite counts was 89.5% (day 28), 94.4% (day 56), and 97.5% (day 84). All study dogs were free of crusts on days 56 and 84. Scales resolved by day 84 in all fluralaner-treated dogs and in three imidacloprid-moxidectin-treated dogs. All fluralaner-treated dogs and five imidacloprid-moxidectin-treated dogs had > 90% hair regrowth on day 84.ConclusionThree consecutive monthly orally administered treatments with fluralaner (5.46% w/w) flavored chewable tablets (minimum dose rate 10 mg/kg body weight) eliminatedDemodex canismites from dogs diagnosed with generalized demodicosis.Graphical Abstract