bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitral valve re-repair vs replacement following failed initial repair: a systematic review and meta-analysis
Authors: Veerappan Muthu , Cheekoty Prashasth , Sazzad Faizus , Kofidis Theo 
Published: October 2020

Abstract
Background
The optimal treatment strategy following a failed mitral valve repair remains unclear. This study aims to compare and analyse available studies which report the clinical outcomes post mitral valve re-repair (MVr) or replacement (MVR) after a prior mitral valve repair.

Methods
Based on PRISMA guidelines, a literature search was performed utilising PubMed, Cochrane and Scopus databases to identify retrospective cohort studies that reported outcomes of MVr and MVR after a prior mitral valve repair. Data regarding operative mortality, clinical outcomes and complications were extracted, synthesized and meta-analysed where appropriate.

Results
Eight studies with a total cohort of 1632 patients were used. After analysis, no significant differences in the short term and long-term operative mortality, incidence of stroke, congestive heart failure, Grade 1 and Grade 2 mitral regurgitation, requirement of 3rd mitral valve operation and reoperation due bleeding were found between the two groups. However, a slightly higher incidence of postoperative atrial fibrillation (OR: 0.11, CI: 0.02 to 0.17, I2 = 0%, p = 0.02) was observed in the MVR group, as compared to the MVr group.

Conclusion
MVr appears to be a viable alternative to MVR for mitral valve reoperation, given that they are associated with similar post-operative outcomes.
Salvage surgery for stage IVa thymic carcinoma combined with aortic arch resection – case report
Authors: Yamato Hiroyuki , Funaki Soichiro , Shimamura Kazuo , Kin Keiwa , Kuratani Toru , Sawa Yoshiki , Shintani Yasushi 
Published: October 2020

Abstract
Background
Although complete surgical resection of thymic carcinoma is a prognostic factor, extended surgery combined with a major blood vessel procedure remains controversial because of the increased risk of mortality. We report a case of Stage IVa thymic carcinoma successfully resected with a pneumonectomy along with aortic arch replacement after chemotherapy.

Case presentation
A 45-year-old male was diagnosed with thymic carcinoma invasion to the aortic arch and left pulmonary artery. Malignant pericardial effusion was also noted, though disappeared after chemotherapy, thus surgical options were considered. A radical resection procedure including left pneumonectomy, aortic arch replacement with total rerouting of the supra-arch vessels, and right pulmonary artery plication was performed. The postoperative course was uneventful and the patient has been disease-free for 3 years.

Conclusion
Extended salvage surgery might be a valuable option for advanced thymic carcinoma.
Biochemical and genetic approaches to the prenatal diagnosis of propionic acidemia in 78 pregnancies
Authors: Dai Mengyao , Xiao Bing , Zhang Huiwen , Ye Jun , Qiu Wenjuan , Zhu Hong , Wang Lei , Liang Lili , Zhan Xia , Ji Wenjun , Wang Yu , Yu Yongguo , Gu Xuefan , Han Lianshu 
Published: October 2020

Abstract
Background
Propionic acidemia (PA) is a serious metabolic disorder, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability and validity of a biochemical strategy in the prenatal diagnosis of PA, we conducted a retrospective study of our 11-year experiences at a single center.

Methods
We accumulated data from 78 pregnancies from 58 families referred to our center and provided prenatal diagnosis by directed genetic analysis and/or metabolite measurement using tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GC/MS) of amniotic fluid (AF) samples.

Results
Sixty-five unaffected fetuses (83.33%) and 13 affected fetuses (16.67%) were confirmed in our study. The characteristic metabolites including propionylcarnitine (C3) level, C3/acetylcarnitine (C2) ratio and 2-methylcitric acid (2MCA) level in unaffected and affected groups showed significant differences (P < 0.0001), while the level of 3-hydroxypropionic acid (3HPA) showed no significant difference between the two groups (P > 0.05).Of the 78 pregnancies, 24 fetuses were found to have either one causative pathogenic variant or were without genetic information in the proband. Three of these fetuses had elevated AF levels of C3, C3/C2 ratio, and 2MCA and, thus, were determined to be affected, while the remaining fetuses were determined to be unaffected based on a normal AF metabolite profile. Our genetic and biochemical results were highly consistent with postnatal follow-up results on all unaffected fetuses.

Conclusions
We conclude that a biochemical approach can serve as a fast and convenient prenatal diagnostic method for pregnancies at an increased risk for PA, which could be used in conjunction with genetic testing for precise prenatal diagnosis of this disorder. In our analysis, the characteristic metabolites C3 level, C3/C2 ratio, and 2MCA level in AF supernatant were dependable biochemical markers for diagnosis, of which the C3/C2 ratio appears to be the most reliable biochemical marker for the prenatal diagnosis of PA.
Personal values in adolescence and their associations with metabolic biomarkers in adulthood: a Japanese population-based study
Authors: Sasaki Natsu , Watanabe Kazuhiro , Kawakami Norito 
Published: October 2020

Abstract
Background
Personal values, which are formed in early life, can have an impact on health outcome later in life.

Objective
The aim of this study is to investigate the relation between personal values in adolescence and bio-indicators related to metabolic syndrome (MetS) in adulthood.

Participants and Methods
The longitudinal data used was from the Japanese Study on Stratification, Health, Income, and Neighborhood (J-SHINE). Personal values in adolescence were retrospectively obtained in 2017 from a self-reporting questionnaire, composed of value priorities and commitment to the values. Venous samples were collected in 2012 for low and high-density lipoprotein (LDL, HDL) cholesterol and hemoglobin A1c (HbA1c). Body mass index (BMI), waist circumference and systolic and diastolic blood pressure (SBP, DBP) were also measured. The associations of each variable were examined by partial correlation analysis. In addition, multiple linear regression analysis was conducted to examine overall associations between personal values and the sum of standardized scores (Z-score) of the biomarkers as a proxy of MetS.

Results
The total population (n = 668) included 261 men and 407 women. For men, the personal value priority of “Having influence on society” was associated with high HDL cholesterol (0.133, p = 0.032) and “Cherishing familiar people” with low waist circumference (r = -0.129, p = 0.049), low SBP, and high DBP (r = -0.135, p = 0.039; r = 0.134, p = 0.041). For women, “Not bothering others” was associated with high SBP and low DBP (r = 0.125, p = 0.015; r = -0.123, p = 0.017). "Economically succeeding" was associated with a worse outcome (β = 0.162, p = 0.042) in men.

Conclusions
Although some significant associations were found between personal values in adolescence and MetS-related markers in adulthood, the overall associations were not strong. Culturally prevailing values were likely to be associated with a good outcome of metabolic health.
Fear response-based prediction for stress susceptibility to PTSD-like phenotypes
Authors: Jeong Min-Jae , Lee Changhee , Sung Kibong , Jung Jung Hoon , Pyo Jung Hyun , Kim Joung-Hun 
Published: October 2020

AbstractMost individuals undergo traumatic stresses at some points in their life, but only a small proportion develop stress-related disorders such as anxiety diseases and posttraumatic stress disorder (PTSD). Although stress susceptibility is one determinant of mental disorders, the underlying mechanisms and functional implication remain unclear yet. We found that an increased amount of freezing that animals exhibited in the intertrial interval (ITI) of a stress-enhanced fear learning paradigm, predicts ensuing PTSD-like symptoms whereas resilient mice show ITI freezing comparable to that of unstressed mice. To examine the behavioral features, we developed a systematic analytical approach for ITI freezing and stress susceptibility. Thus, we provide a behavioral parameter for prognosis to stress susceptibility of individuals in the development of PTSD-like symptoms as well as a new mathematical means to scrutinize freezing behavior.
Targeting tumor hypoxia and mitochondrial metabolism with anti-parasitic drugs to improve radiation response in high-grade gliomas
Authors: Mudassar Faiqa , Shen Han , O’Neill Geraldine , Hau Eric 
Published: October 2020

AbstractHigh-grade gliomas (HGGs), including glioblastoma and diffuse intrinsic pontine glioma, are amongst the most fatal brain tumors. These tumors are associated with a dismal prognosis with a median survival of less than 15 months. Radiotherapy has been the mainstay of treatment of HGGs for decades; however, pronounced radioresistance is the major obstacle towards the successful radiotherapy treatment. Herein, tumor hypoxia is identified as a significant contributor to the radioresistance of HGGs as oxygenation is critical for the effectiveness of radiotherapy. Hypoxia plays a fundamental role in the aggressive and resistant phenotype of all solid tumors, including HGGs, by upregulating hypoxia-inducible factors (HIFs) which stimulate vital enzymes responsible for cancer survival under hypoxic stress. Since current attempts to target tumor hypoxia focus on reducing oxygen demand of tumor cells by decreasing oxygen consumption rate (OCR), an attractive strategy to achieve this is by inhibiting mitochondrial oxidative phosphorylation, as it could decrease OCR, and increase oxygenation, and could therefore improve the radiation response in HGGs. This approach would also help in eradicating the radioresistant glioma stem cells (GSCs) as these predominantly rely on mitochondrial metabolism for survival. Here, we highlight the potential for repurposing anti-parasitic drugs to abolish tumor hypoxia and induce apoptosis of GSCs. Current literature provides compelling evidence that these drugs (atovaquone, ivermectin, proguanil, mefloquine, and quinacrine) could be effective against cancers by mechanisms including inhibition of mitochondrial metabolism and tumor hypoxia and inducing DNA damage. Therefore, combining these drugs with radiotherapy could potentially enhance the radiosensitivity of HGGs. The reported efficacy of these agents against glioblastomas and their ability to penetrate the blood-brain barrier provides further support towards promising results and clinical translation of these agents for HGGs treatment.
Outcome of two pairs of monozygotic twins with pleuropulmonary blastoma: case report
Authors: Zhang Shihan , Wang Xisi , Li Sihui , Cai Siyu , Yu Tong , Fu Libing , Zhang Na , Peng Xiaoxia , Zeng Qi , Ma Xiaoli 
Published: October 2020

Abstract
Background
Pleuropulmonary blastomas (PPB) are rare aggressive paediatric lung malignancies and are among the most common DICER1-related disorders: it is estimated that 75–80% of children with a PPB have the DICER1 mutation. DICER1 mutations are responsible for familial tumour susceptibility syndrome with an increased risk of tumours. In approximately 35% of families with children manifesting PPB, further malignancies may be observed. Symptoms of DICER1 syndrome may vary, even within monozygotic twins. Preventive screening of carriers with DICER1 mutations is important and follow-up is undertaken as recommended by the 2016 International PPB Register.

Case presentation
We present two pairs of monozygotic twins. In one pair of 4-year, 2-month old girls, both with DICER1 mutation, one developed PPB(II) and her identical sibling had acute transient hepatitis. In the other pair of 19-month-old female babies, one had a history of bronchopulmonary hypoplasia and developed PPB(III) without DICER1 mutation, and her identical sibling had allergic asthma. Both patients with PPB were treated with R0 resection and received 12 cycles of postoperative chemotherapy. At the most recent review, the twins had been followed up for six and eight years, respectively, and they all remained healthy. However, the height and weight of the patients with PPB were lower than those of their respective identical sister.

Conclusions
PPB is rare, especially in monozygotic twins. We emphasise the importance of genetic testing and follow-up in monozygotic twins with PPB. During the follow-up, children surviving PPB should be monitored closely for growth and development disorders which caused by chemotherapy.
Identification of bronchiolitis profiles in Italian children through the application of latent class analysis
Authors: Ferrante Giuliana , Fondacaro Carmela , Cilluffo Giovanna , Dones Piera , Cardella Francesca , Corsello Giovanni 
Published: October 2020

AbstractBackgroundBronchiolitis is the primary infection of the lower respiratory tract in children under 2 years of age. Although it is generally considered a single nosological entity, recent studies suggested remarkable clinical heterogeneity. To date, no studies have identified classes of children with bronchiolitis within the Italian population. This study aimed to identify discrete profiles of Italian children hospitalized with bronchiolitis using a clustering approach and to compare findings with those obtained in international cohorts.MethodsThis was a retrospective single-centre study conducted on children aged ≤2 years hospitalised with bronchiolitis (n = 401) at the Department of Infectious Diseases and the University Department of General Pediatrics in “Giovanni Di Cristina” Pediatric Hospital of Palermo, Italy, between November 2012 and May 2019. Bronchiolitis profiles were determined by latent class analysis, classifying children based on clinical characteristics at admission and viral aetiology.ResultsThree profiles were identified. Class 1 (49%) was composed of 45% male children; all children were aged ≤6 months at hospitalization; 77% were infected with RSV; 100% had respiratory distress, 11% had apnea and none had cough. Class 2 (77%) was mainly composed of male subjects (51%); 19% were aged > 6 months at admission; 37% were infected with RSV; 12% had respiratory distress, 5% had apnea and 90% had cough. Class 3 (19%) included the largest proportion of male subjects (94%) and was mostly composed of children aged > 6 months at the time of admission (68%); 70% had cough, 12% showed respiratory distress and none presented with apnoea. Children in Class 1 were more frequently born near the epidemic season (p = 0.028); breastfeeding duration was significantly longer for children in Class 3 (p = 0.004).ConclusionsThe study identified distinct clinical profiles of bronchiolitis by a clustering approach in a single-centre study of children hospitalised for bronchiolitis in Italy. The three bronchiolitis profiles share some similarities with those identified in international studies using the same statistical approach. These findings may help to increase the understanding of the phenotypic variability that typically characterizes bronchiolitis, with relevant implications for future research.
Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway
Authors: Liu Jing , Saiyin Wuliji , Xie Xiaohua , Mao Limin , Li Lili 
Published: October 2020

Abstract
Background
Amelogenesis imperfecta (AI) is a type of hereditary diseases that manifest defects in the formation or mineralization of enamel. Recently, it is reported that inactivation of FAM20C, a well-known Golgi casein kinase, caused AI. However, the mechanism of it is still unknown. The aim of this study was to explore the molecular mechanism of AI, which caused by ablation of FAM20C.

Results
In the Sox2-Cre;Fam20Cfl/fl (cKO) mouse, we found abnormal differentiation of ameloblasts, improper formation and mineralization of enamel, and downregulation of both mRNA and protein level of enamel matrix proteins, including amelogenin (AMEL), ameloblastin (AMBN) and enamelin (ENAM). The levels of BMP2, BMP4 and BMP7, the ligands of BMP signaling pathway, and phosphorylation of Smad1/5/8, the key regulators of BMP signaling pathway, were all decreased in the enamel matrix and the ameloblast of the cKO mice, respectively. The expression of cyclin-dependent kinase inhibitor (P21), muscle segment homeobox genes 2 (Msx2), which are the target genes of the BMP signaling pathway, and laminin 3, the downstream factor of Msx2, were all significantly decreased in the ameloblasts of the cKO mice compared to the control mice.

Conclusion
the results of our study suggest that ablation of FAM20C leads to AI through inhibiting the Smad dependent BMP signaling pathway in the process of amelogenesis.
Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan
Authors: Jakobsen Janus Christian , Dankiewicz Josef , Lange Theis , Cronberg Tobias , Lilja Gisela , Levin Helena , Bělohlávek Jan , Callaway Clifton , Cariou Alain , Erlinge David , Hovdenes Jan , Joannidis Michael , Nordberg Per , Oddo Mauro , Pelosi Paolo , Kirkegaard Hans , Eastwood Glenn , Rylander Christian , Saxena Manoj , Storm Christian , Taccone Fabio Silvio , Wise Matthew P. , Morgan Matt P. G. , Young Paul , Nichol Alistair , Friberg Hans , Ullén Susann , Nielsen Niklas 
Published: October 2020

Abstract
Background
To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.

Methods/design
The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33 °C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥ 37.8 °C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180 days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4–6) at 180 days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.

Discussion
This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
Should the nail plate be replaced or discarded after nail bed repair in children? Nail bed INJury Analysis (NINJA) randomised controlled trial: a health economic and statistical analysis plan
Authors: Stokes Jamie R. , Png May Ee , Jain Abhilash , Greig Aina V. H. , Shirkey Beverly A. , Dritsaki Melina , Cook Jonathan A. 
Published: October 2020

AbstractBackgroundNail bed trauma is one of the most common surgically treated paediatric hand injuries in the UK. Despite surgeons generally expressing a preference to replace the nail plate after repairing the nail bed, there is limited evidence to support this practice. We describe a statistical and health economic analysis plan (SHEAP) for the Nail bed INJury Analysis (NINJA) randomised controlled trial.Methods/designNINJA is a multicentre, pragmatic, superiority, parallel group randomised controlled trial of the treatment of nail bed injury in participants 16 years old or younger. The study aims to evaluate the efficacy and cost-effectiveness of replacing the nail plate compared to discarding it following the repair of a nail bed injury. Surgical site infection at 7–10 days post-randomisation and cosmetic appearance of the nail are the co-primary outcomes for NINJA. Surgical site infection at 7–10 days post-randomisation will be evaluated using a logistic regression model adjusting for site as the sole stratification factor and allowing for intra-site correlation. Cosmetic appearance will be assessed via the newly developed Oxford Finger Nail Appearance Score and will be evaluated by use of a Mann-WhitneyUtest. An ordinal logistic regression model will also be used to assess the Oxford Finger Nail Appearance Score, adjusting for site and allowing for intra-site correlation. Secondary outcomes are measured at 7–10 days and 4 months and include the EQ-5D-Y questionnaire, pain at first dressing change, cost-effectiveness, late surgical site infection, and participant/parent satisfaction with nail healing. Missing primary outcome data will be summarised by treatment arm and investigated through a sensitivity analysis. Full details of the planned methods of analysis and descriptive statistics are described in this paper. The NINJA study protocol has been published previously.DiscussionThe planned analysis strategy for the NINJA trial has been set out here to reduce the risk of reporting bias and data-driven analysis. Any deviations from the SHEAP described in this paper will be detailed and justified fully in the final report of the trial.Trial registrationISRCTN,ISRCTN44551796. Registered on 23 April 2018.