bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and wearability evaluation of a fully portable wrist exoskeleton for unsupervised training after stroke
Authors: Lambelet Charles , Temiraliuly Damir , Siegenthaler Marc , Wirth Marc , Woolley Daniel G. , Lambercy Olivier , Gassert Roger , Wenderoth Nicole
Published: October 2020

Background

Chronic hand and wrist impairment are frequently present following stroke and severely limit independence in everyday life. The wrist orientates and stabilizes the hand before and during grasping, and is therefore of critical importance in activities of daily living (ADL). To improve rehabilitation outcomes, classical therapy could be supplemented by novel therapies that can be applied in unsupervised settings. This would enable more distributed practice and could potentially increase overall training dose. Robotic technology offers new possibilities to address this challenge, but it is critical that devices for independent training are easy and appealing to use. Here, we present the development, characterization and wearability evaluation of a fully portable exoskeleton for active wrist extension/flexion support in stroke rehabilitation.

Methods

First we defined the requirements, and based on these, constructed the exoskeleton. We then characterized the device with standardized haptic and human-robot interaction metrics. The exoskeleton is composed of two modules placed on the forearm/hand and the upper arm. These modules weigh 238 g and 224 g, respectively. The forearm module actively supports wrist extension and flexion with a torque up to 3.7 Nm and an angular velocity up to 530 deg/s over a range of 154∘. The upper arm module includes the control electronics and battery, which can power the device for about 125 min in normal use. Special emphasis was put on independent donning and doffing of the device, which was tested via a wearability evaluation in 15 healthy participants and 2 stroke survivors using both qualitative and quantitative methods.

Results

All participants were able to independently don and doff the device after only 4 practice trials. For healthy participants the donning and doffing process took 61 ±15 s and 24 ±6 s, respectively. The two stroke survivors donned and doffed the exoskeleton in 54 s/22 s and 113 s/32 s, respectively. Usability questionnaires revealed that despite minor difficulties, all participants were positive regarding the device.

Conclusions

This study describes an actuated wrist exoskeleton which weighs less than 500 g, and which is easy and fast to don and doff with one hand. Our design has put special emphasis on the donning aspect of robotic devices which constitutes the first barrier a user will face in unsupervised settings. The proposed device is a first and intermediate step towards wearable rehabilitation technologies that can be used independently by the patient and in unsupervised settings.
Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2+
Authors: Berggrund Malin , Gustavsson Inger , Aarnio Riina , Lindberg Julia Hedlund , Sanner Karin , Wikström Ingrid , Enroth Stefan , Bunikis Ignas , Olovsson Matts , Gyllensten Ulf
Published: October 2020

Background

The vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables.

Methods

In total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software.

Results

K-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036).

Conclusions

The vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.
Effect of Curcuma zedoaria hydro-alcoholic extract on learning, memory deficits and oxidative damage of brain tissue following seizures induced by pentylenetetrazole in rat
Authors: Mahmoudi Touran , Lorigooini Zahra , Rafieian-kopaei Mahmoud , Arabi Mehran , Rabiei Zahra , Bijad Elham , Kazemi Sedigheh
Published: October 2020

Background

Previous studies have shown that seizures can cause cognitive disorders. On the other hand, the Curcuma zedoaria (CZ) has beneficial effects on the nervous system. However, there is little information on the possible effects of the CZ extract on seizures. The aim of this study was to investigate the possible effects of CZ extract on cognitive impairment and oxidative stress induced by epilepsy in rats.

Methods

Rats were randomly divided into different groups. In all rats (except the sham group), kindling was performed by intraperitoneal injection of pentylenetetrazol (PTZ) at a dose of 35 mg/kg every 48 h for 14 days. Positive group received 2 mg/kg diazepam + PTZ; treatment groups received 100, 200 or 400 mg/kg CZ extract + PTZ; and one group received 0.5 mg/kg flumazenil and CZ extract + PTZ. Shuttle box and Morris Water Maze tests were used to measure memory and learning. On the last day of treatments PTZ injection was at dose of 60 mg/kg, tonic seizure threshold and mortality rate were recorded in each group. After deep anesthesia, blood was drawn from the rats’ hearts and the hippocampus of all rats was removed.

Results

Statistical analysis of the data showed that the CZ extract significantly increased the tonic seizure threshold and reduced the pentylenetetrazol-induced mortality and the extract dose of 400 mg/kg was selected as the most effective dose compared to the other doses. It was also found that flumazenil (a GABAA receptor antagonist) reduced the tonic seizure threshold compared to the effective dose of the extract. The results of shuttle box and Morris water maze behavioral tests showed that memory and learning decreased in the negative control group and the CZ extract treatment improved memory and learning in rats. The CZ extract also increased antioxidant capacity, decreased MDA and NO in the brain and serum of pre-treated groups in compared to the negative control group. Conclusion: It is concluded that the CZ extract has beneficial effects on learning and memory impairment in PTZ-induced epilepsy model, which has been associated with antioxidant effects in the brain or possibly exerts its effects through the GABAergic system.
The socio-cultural significance of mineral licks to the Maijuna of the Peruvian Amazon: implications for the sustainable management of hunting
Authors: Gilmore Michael P. , Griffiths Brian M. , Bowler Mark
Published: October 2020

Background

The overhunting of wild species is a major threat to biodiversity in the Amazon; yet, managed, sustainable hunting is widely considered part of the solution to conserving wildlife populations. Hunting is both a culturally important activity for Indigenous people and provides an important food source. Mineral licks, a focal point of hunting in Amazonia, are naturally occurring areas in the forest where animals come to obtain essential minerals or clays that are thought to neutralize plant-based alkaloids. We sought to better understand the socio-cultural importance of mineral licks to the Maijuna Indigenous group to inform the sustainable management of this habitat and associated wildlife populations.

Methods

Semi-structured interviews, focus groups, and participatory mapping were carried out with hunters to assess the significance of mineral licks and their associated animal resources as well as to determine how the relationship that the Maijuna have with mineral licks has changed over time.

Results

Mineral licks are culturally significant and useful to the Maijuna in a variety of ways. Hunters target these areas year-round both during the day and night, and animals killed are consumed for subsistence and sold to generate income. The spatial use of mineral licks across the landscape is determined on the generational family level, with families maintaining exclusive use of selected mineral licks and excluding access by other hunters. The Maijuna also have traditional beliefs for why animals visit mineral licks, which is linked to the traditional Maijuna story of the creation of the first tapir. The relationship that the Maijuna have with mineral licks has changed considerably over time, which is observed through changes in hunting technologies and methods as well as the loss of traditional knowledge and beliefs.

Conclusions

Traditional and current Maijuna hunting conventions, in which families maintain exclusive use of selected mineral licks, likely reduce the probability of overexploitation of animal populations. Community-based management plans for mineral licks in Maijuna lands and beyond must incorporate and account for the multiple cultural and economic needs of local communities while also striving toward ecological sustainability. Country-wide strategies to conserving forests and using them sustainably should aim to ensure land tenure for rural peoples and encourage management that incorporates traditional sustainable hunting conventions.
Serum globulin and albumin to globulin ratio as potential diagnostic biomarkers for periprosthetic joint infection: a retrospective review
Authors: Ye Yongyu , Chen Weishen , Gu Minghui , Xian Guoyan , Pan Baiqi , Zheng Linli , Zhang Ziji , Sheng Puyi
Published: October 2020

Background

Periprosthetic joint infection (PJI) has been increasingly documented; however, its preoperative accurate diagnosis remains challenging. Furthermore, there is a dire need to identify appropriate and effective biomarkers. We aimed to evaluate the relationship between globulin, albumin to globulin (A/G) ratio, and development of PJI in patients undergoing revision total joint arthroplasty (TJA).

Methods

A retrospective study was conducted on patients who had undergone revision TJA between 2011 and 2018 (89 with aseptic mechanic failure and 38 with PJI). The serum proteins were explored using univariate analysis followed by multivariate logistic regression. The diagnostic performance of these proteins was assessed by the receiver operating characteristic (ROC) curve.

Results

Higher globulin levels (odds ratio [OR], 1.239; P < 0.001) and lower A/G ratio (OR, 0.007; P < 0.001) were strongly associated with the risk of PJI. ROC curve analysis demonstrated reasonable diagnostic performance for globulin (area under the curve [AUC], 0.77; sensitivity, 78.95%; and specificity, 69.66%) and A/G ratio (AUC, 0.779; sensitivity, 65.79%; and specificity, 78.65%).

Conclusions

Both globulin and A/G ratio were associated with PJI and may serve as potential adjuvant biomarkers in the diagnosis of PJI.
Evaluation of risk correlation between recurrence of patellar dislocation and damage to the medial patellofemoral ligament in different sites caused by primary patellar dislocation by MRI: a meta-analysis
Authors: Jiang Boyong , Qiao Chenggang , Shi Yuting , Ren Yizhong , Han Changxu , Zhu Yong , Na Yuyan
Published: October 2020

Purpose

Non-surgical treatment of primary patellar dislocation has a high risk of recurrent dislocation; thus, we tried to identify injuries in which sites of the medial patellofemoral ligament (MPFL) were most associated with recurrent dislocation by analyzing relevant original literature in order to provide improved suggestions on early surgical treatment.

Methods

According to the preset retrieval strategy, the original studies were retrieved until January 2020 using MEDLINE, Embase and Cochrane Library. Review Manager 5.3 software was used to summarize and compare the differences of recurrent dislocation of MPFL injuries at different attachments.

Results

Although the incidence of recurrent patellar dislocation at the femoral attachment of MPFL was higher overall (femoral only vs. patellar only vs. combined: 37.6% vs. 32.3% vs. 35.8%), no statistical difference was found among the three groups (femoral only vs. patellar only, RR = 1.32 [95% CI 0.89–1.95];P= 0.17) (femoral only vs. combined, RR = 1.15 [95% CI 0.59–2.22];P= 0.68) (patellar only vs. combined, RR = 0.94 [95% CI 0.69–1.29];P= 0.72). In addition, the sulcus angle of recurrent dislocation group is significantly greater than that in the non-recurrent dislocation group (MD = 3.06 [95% CI 0.42–5.70];P= 0.02).

Conclusions

Based on the pooled data collected from the original studies available, the risk of recurrent patellar dislocation due to damage to the MPFL at different sites did not differ. Additionally, the sulcus angle in the group with recurrent dislocation was considerably higher when comparing with the group without recurrent dislocation, that is, the shallower and flatter of the trochlear groove, the higher the risk of recurrent patellar dislocation.
Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis
Authors: Haythorn Abigail , Young Madeline , Stanton James , Zhang Jian , Mueller P. O. E. , Halper Jaroslava
Published: October 2020

Background

Equine degenerative suspensory ligament desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments, leads to progressive and debilitating lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous studies suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGFβ) family, impacting synthesis of proteoglycans. To identify potential players in pathogenesis of DSLD a new approach utilizing next generation sequencing was undertaken.

Methods

Next generation sequencing was performed using RNA extracted from skin biopsies of six control Peruvian Pasos and six horses with DSLD (4 Peruvian Pasos and 2 warmbloods). The CuffDiff result sets were validated with algorithms used to run them. This was based on the determined false discovery rates derived from thePvalues adjusted for multiple testing for any given result.

Results

Bioinformatics analysis of transcriptomes revealed differential expression of over 1500 genes, including increased expression of genes for several growth factors (most prominently BMP2, FGF5, CTGF, many members of the EGF family), and mediators of signaling (Fos, Myc, MAPK system), and keratins. Two genes encoding for enzymes involved in synthesis of hyaluronan were also overexpressed. Gene expression was decreased for protein cores of many proteoglycans, several growth factors, most collagens, and many peptides with immune function.

Conclusions

The overexpression ofBMP2correlates well with our previous data. However, the decrease in expression of numerous proteoglycans was unexpected. A mutation in a gene of a less characterized proteoglycan and/or glycosyltransferase with subsequent increased production of hyaluronan and/or a proteoglycan(s) undetected in our study could account for the systemic proteoglycan deposition. Decreased collagen gene expression indicates abnormal connective tissue metabolism. The increased expression of keratin genes andFGF5supports reports of skin abnormalities in DSLD. Underexpression of immune function genes corresponds with lack of inflammation in DSLD tissues. Finally, though the proteoglycan and/or glycosaminoglycan abundant in DSLD has not been identified, we validated our previous data, including overexpression ofBMP2, and systemic nature of DSLD due to disturbed metabolism of the extracellular matrix.
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

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

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

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

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

Most 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

High-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

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

Background

Bronchiolitis 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.

Methods

This 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.

Results

Three 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).

Conclusions

The 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

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

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

Background

Nail 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/design

NINJA 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.

Discussion

The 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 registration

ISRCTN,ISRCTN44551796. Registered on 23 April 2018.
Early migration of stemless and stemmed humeral components after total shoulder arthroplasty for osteoarthritis—study protocol for a randomized controlled trial
Authors: Nyring Marc Randall Kristensen , Olsen Bo S. , Yilmaz Müjgan , Petersen Michael M. , Flivik Gunnar , Rasmussen Jeppe V.
Published: October 2020

Background

Glenohumeral osteoarthritis can, in the most severe cases, require surgery with insertion of a shoulder arthroplasty. A design with a stem in the humeral bone canal is currently regarded as the standard treatment option in patients who have an intact rotator cuff function, but complications related to the stem including humeral fractures can have devastating consequences. By using a stemless humeral component, stem-related complications can be reduced. The aim of this study is to compare the Comprehensive Nano stemless total shoulder arthroplasty (intervention group) with the Comprehensive stemmed total shoulder arthroplasty (control group).

Materials and methods

This is a randomized controlled trial comparing the stemless and the stemmed total shoulder arthroplasty. All Danish citizens with glenohumeral osteoarthritis indicating a total shoulder arthroplasty referred to the orthopedic department at Copenhagen University Hospital in Herlev/Gentofte will be offered participation. The following exclude from participation: below 18 years of age, cognitive or linguistic impairment, insufficient function of the rotator cuff, poor bone quality, and ASA groups 4–5. A total of 122 patients will be included of which 56 will be part of a radiostereometric analysis (RSA) study of humeral component migration. The primary outcomes are magnitude of migration of the humeral component assessed by RSA and patient-reported outcome by Western Ontario Osteoarthritis of the Shoulder index (WOOS). The secondary outcomes are additional patient-reported outcomes, functional outcome, readmission, complications, revisions, and changes in bone mineral density (BMD) of the proximal humerus assessed by duel energy x-ray absorptiometry (DXA) and economy (cost-utility analysis). The patients are examined before the operation and 3, 6, 12, and 24 months postoperative.

Discussion

To our knowledge, RSA has never been used to access migration of a stemmed or a stemless humeral component nor has the stemmed and the stemless humeral component been compared with regard to pain relief and shoulder function in a randomized clinical trial. Today, the two designs are considered equal in the treatment of osteoarthritis. The study will provide surgeons and patients with information about shoulder arthroplasty for osteoarthritis and assist them in decision-making.

Trial registration

ClinicalTrials.govNCT04105478. Registered on 25 September 2019
Spinal cord stimulation for chronic intractable trunk or limb pain: study protocol for a Chinese multicenter randomized withdrawal trial (CITRIP study)
Authors: Lu Yang , Mao Peng , Wang Guihuai , Tao Wei , Xiong Donglin , Ma Ke , Li Rongchun , Feng Dan , Duan Wanru , Li Shun , Fu Zhijian , Feng Zhiying , Jin Yi , Wan Li , Lu Yan , Zhang Daying , Fan Bifa , Wang James Jin , Li Luming
Published: October 2020

Background

Although effective results of many studies support the use of spinal cord stimulation in chronic pain patients, no randomized controlled trial has been undertaken in China to date. CITRIP is a multicenter, prospective, randomized, withdrawal study designed to evaluate the clinical effectiveness and safety of spinal cord stimulation plus remote programming management in patients with intractable trunk or limb pain.

Method

Participants will be recruited in approximately 10 centers across China. Eligible participants with intractable trunk or limb and an average visual analog scale (VAS) score ≥ 5 will undergo a spinal cord stimulation test. Participants with VAS score reduction ≥ 50% could move forward to receive implantation of an implanted pulse generator. In the withdrawal period at 3-month follow-up visit, participants randomized to the experimental group (EG) will undergo continuous stimulation while ceasing the stimulation in the control group (CG). The outcome assessment will occur at baseline and at 1, 3 (pre- and post-randomization), and 6 months. The primary outcome is the difference of maximal VAS score between EG and CG in the withdrawal period compared with baseline before the withdrawal period. Additional outcomes include VAS score change at 1-, 3-, and 6-month follow-ups; responder rate (VAS score improving by 50%); achievement rate of a desirable pain state (VAS score ≤ 4); awake times during sleep; Beck Depression Inventory for depression evaluation; short-form 36 for quality of life evaluation; drug usage; and satisfaction rating of the device. Adverse events will be collected. The primary analysis will follow the intention-to-treat principle.

Discussion

The CITRIP study seeks to evaluate the effectiveness and safety of a randomized withdrawal trial of spinal cord stimulation for patients with intractable trunk or limb pain.

Trial registration

ClinicalTrials.gov NCT03858790. Registered on March 1, 2019, retrospectively registered
Assessing the acoustic behaviour of Anopheles gambiae (s.l.) dsxF mutants: implications for vector control
Authors: Su Matthew P. , Georgiades Marcos , Bagi Judit , Kyrou Kyros , Crisanti Andrea , Albert Joerg T.
Published: October 2020

Background

Release of gene-drive mutants to suppressAnophelesmosquito reproduction is a promising method of malaria control. However, many scientific, regulatory and ethical questions remain before transgenic mosquitoes can be utilised in the field. At a behavioural level, gene-drive carrying mutants should be at least as sexually attractive as the wildtype populations they compete against, with a key element ofAnophelescopulation being acoustic courtship. We analysed sound emissions and acoustic preference in adoublesexmutant previously used to collapseAnopheles gambiae(s.l.) cages.

Methods

Anophelesrely on flight tones produced by the beating of their wings for acoustic mating communication. We assessed the impact of disrupting a female-specific isoform of thedoublesexgene (dsxF) on the wing beat frequency (WBF; measured asflight tone) of males (XY) and females (XX) in homozygousdsxF−mutants (dsxF−/−), heterozygousdsxF−carriers (dsxF+/−) and G3dsxF+controls (dsxF+/+). To exclude non-genetic influences, we controlled for temperature and wing length. We used a phonotaxis assay to test the acoustic preferences of mutant and control mosquitoes.

Results

A previous study showed an altered phenotype only fordsxF−/−females, who appear intersex, suggesting that the female-specificdsxFallele is haplosufficient. We identified significant, dose-dependent increases in the WBF of bothdsxF−/−anddsxF+/−females compared todsxF+/+females. All female WBFs remained significantly lower than male equivalents, though. Males showed stronger phonotactic responses to the WBFs of controldsxF+/+females than to those ofdsxF+/−anddsxF−/−females. We found no evidence of phonotaxis in any female genotype. No male genotypes displayed any deviations from controls.

Conclusions

A prerequisite for anopheline copulation is the phonotactic attraction of males towards female flight tones within mating swarms. Reductions in mutant acoustic attractiveness diminish their mating efficiency and thus the efficacy of population control efforts. Caged population assessments may not successfully reproduce natural mating scenarios. We propose to amend existing testing protocols to better reflect competition between mutants and target populations. Our findings confirm thatdsxFdisruption has no effect on males; for some phenotypic traits, such as female WBFs, the effects ofdsxFappear dose-dependent rather than haplosufficient.
Animal based low carbohydrate diet is associated with increased risk of type 2 diabetes in Tehranian adults
Authors: Sali Sohrab , Farhadnejad Hossein , Asghari Golaleh , Teymoori Farshad , Mirmiran Parvin , Djazayeri Abolghassem , Azizi Fereidoun
Published: October 2020

Background

To investigate the association of low carbohydrate diet (LCD) score with the risk of type 2 diabetes among adults.

Methods

This cohort study was conducted on 4356 healthy participants aged ≥ 19 years old, who were followed-up for a mean duration of 3 years within the framework of the Tehran Lipid and Glucose Study. LCD score was calculated using a food frequency questionnaire according to intake of carbohydrate, protein, and fat at baseline. Diabetes was defined according to the criteria of the American Diabetes Association. Multivariable logistic regression models, adjusted for potential confounders, were used to estimate risk of diabetes across quartiles of LCD score.

Results

Mean ± SD age of the study participants (44.4% men) was 40.5 ± 13.0 years. The median (25–75 interquartile range) of LCD score was 17.0 (12.0–21.0) and after a 3 year follow-up period, 123 (2.8%) incident cases of diabetes were ascertained. After adjustment for confounding variables, including age, sex, smoking status, physical activity, total calorie intake, saturated fatty acid, waist circumference, educational level, and family history of diabetes, the multivariable-adjusted ORs (95% CIs) of type 2 diabetes, comparing the highest with the lowest quartiles, were 2.16 (1.16–4.04) for total LCD score (P-value = 0.015), 1.81 (1.06–3.11) for animal-based LCD score (P-value = 0.029), and 1.47 (0.85–2.52) for plant-based LCD score (P-value = 0.160).

Conclusion

Our findings suggest that a higher adherence to LCD, mostly with higher intakes of protein and fat from animal-source foods, can increase the incidence of diabetes; however, a plant-based low-carbohydrate dietary pattern is not significantly associated with risk of type 2 diabetes.