bluuebunny/crossref_metadata_2025 huggingface dataset:
A collagen membrane influences bone turnover marker in vivo after bone augmentation with xenogenic bone
Authors: Staedt Henning , Dau Michael , Schiegnitz Eik , Thiem Daniel G. E. , Tagadiuc Olga , Palarie Victor , Ottl Peter , Al-Nawas Bilal , Kämmerer Peer W.
Published: December 2020

Background

The aim was to compare early biochemical and histological osseous healing of chronic mandibular defects regenerated with bovine bone substitute with and without collagen membrane in vivo.

Methods

Eight weeks after formation of a lateral full-thickness perforating bone defect in the mandible of 40 rabbits, bovine bone substitute with (“+”;n = 20) and without (“-”;n = 20) collagen membrane was applied. Blood and bone was collected 24, 72 h, 7, 14 and 21 days after surgery. Total acid phosphatase, bone acid phosphatase, total alkaline phosphatase and bone alkaline phosphatase activities were compared between groups. Formation of new bone was quantified histologically for all time points.

Results

Twenty-four hours after surgery, bone alkaline phosphatase was significantly elevated in “+” group when compared to “-” (p=0.012). After 72 hours, all bone turnover markers except for total acid phosphatase (p=0.078) where significantly elevated in “+” (allp < 0.05). Fourteen days after surgery, the significant highest values for all bone turnover markers were detected in “-” (allp < 0.05). A significant difference in favor of group “-” could also be detected after 3 weeks in terms of both acid phosphatases (p < 0.05). In histology, no significant differences could be detected.

Conclusion

Bone regeneration with bovine bone substitute material and collagen membrane shows a significantly earlier bone remodeling activity but does not seem to influence formation of new bone in histological samples.
Factors associated with substance use disorder treatment completion: a cross-sectional analysis of justice-involved adolescents
Authors: Johnson Micah E. , Tran Dieu X.
Published: December 2020

Background

Substance use disorders (SUD) are prevalent among those in the juvenile justice system. SUD treatment programs implemented in correctional settings can prevent overdose and other health-related problems among an underserved health disparity population. However, only a fraction of justice-involved adolescents with SUDs complete a treatment program and the factors associated with treatment completion among adolescents in the criminal justice system have not been thoroughly investigated.

Methods

Using cross-sectional data on 25,587 adolescents from the Florida Department of Juvenile Justice (FLDJJ) who met the criteria for SUD treatment, the study investigated the factors associated with the completion of SUD treatment. Sociodemographic, mental health, and other variables were examined.

Results

Several factors were associated with an increased likelihood of SUD treatment completion: previous participation in treatment programs, prior drug and alcohol education class attendance, and involvement in court-directed programs. Additional factors included multiple incarcerations, and strong financial and support networks.

Conclusions

The strongest factors associated with a higher likelihood of SUD treatment completion among adolescents in the justice system are ones that can be translated into programs and practices. Repeated referrals to treatment, court-directed programs, and strong support networks may yield higher rates of completion.
Supraspinatus tendon transosseous vs anchor repair surgery: a comparative study of mechanical recovery in the rabbit
Authors: Chaler Joaquim , Louati Hakim , Uhthoff Hans K. , Trudel Guy
Published: December 2020

Background

Supraspinatus (SSP) tendon ruptures requiring surgical repair are common. Arthroscopic suture anchor fixation has gradually replaced transosseous repair in supraspinatus tendon tear. Our objective was to compare mechanical properties between transosseous and anchor supraspinatus repair in the first 6 postoperative weeks in a rabbit model.

Methods

One hundred and fifty-two rabbits had one supraspinatus tendon repaired either with an anchor suture 1 week after detachment or with transosseous sutures. Rabbits were euthanized at 0, 1, 2, 4 or 6 postoperative weeks. Experimental and contralateral tendons (304 tendons) were mechanically tested to failure. Data are expressed as percent of contralateral.

Results

Anchor repair had higher loads to failure compared to transosseous repair, at immediate repair (week 0, 52 ± 21% vs 25 ± 17%, respectively; p = 0.004) and at 1 postoperative week (64 ± 32% vs 28 ± 10%; p = 0.003) with no difference after 2 weeks. There was no difference in stiffness. Transosseous repairs showed higher rates of midsubstance failures compared to anchor repairs at 1 (p = 0.004) and 2 postoperative weeks (p < 0.001). Both transosseous and anchor repairs restored supraspinatus mechanical properties after 4 postoperative weeks.

Conclusion

Anchor repair provided better initial tensile strength while transosseous repair led to a faster normalization (namely, midsubstance) of the mode of failure. Research to optimize supraspinatus repair may need to consider the advantages from both surgical approaches.
Correction to: High prevalence of symptomatic spinal stenosis in Norwegian adults with achondroplasia: a population-based study
Authors: Fredwall Svein O. , Steen Unni , de Vries Olga , Rustad Cecilie F. , Eggesbø Heidi Beate , Weedon-Fekjær Harald , Lidal Ingeborg B. , Savarirayan Ravi , Månum Grethe
Published: December 2020

An amendment to this paper has been published and can be accessed via the original article.
Electrocution as an alternative euthanasia method to blunt force trauma to the head followed by exsanguination for non-viable piglets
Authors: Husheer Johannes , Luepke Matthias , Dziallas Peter , Waldmann Karl-Heinz , von Altrock Alexandra
Published: December 2020

Background

On farms, the currently approved and most widely practised method of euthanising non-viable piglets is blunt force trauma to the head followed by exsanguination. However, the use of this method is criticised due to public perceptions and aversion to the methodology by caretakers. Therefore, electrocution after electrical stunning was examined as an alternative approach in 80 hybrid piglets. Initially, electrocution was simulated with finite element analysis using a computer piglet-model, where current density in the heart was visualised and size and position of the electrodes were defined. The following step investigated electrical parameters for electrocution in anaesthetised piglets; first, with a constant voltage power source and then with a constant current power source. The electrical stunning was examined using the constant current supply. Finally, the results of electrical stunning and electrocution were verified in 25 healthy piglets with a body weight between 1 and 2 kg. Unconsciousness was proven by testing palpebral, corneal and nociceptive reflexes. Time of death was confirmed by electroencephalography (EEG) and electrocardiography (ECG) records.

Results

Stunning succeeded with the preset of 1.3 A and 50 Hz, placing the electrodes on both sides of the head between the eyes and ears using different timespans between 8 and 20 s. Prolonged electrical flow resulted in reduced paddling movements after the epileptic seizure, and allowed undisturbed reflex tests and installation of electrodes for EEG and ECG recording during electrocution. Using 0.75 A and 400 Hz, pin-shaped electrodes were first positioned on both sides of the chest for 5 s, followed by a break of 20–30 s and a second current flow, whereby the electrodes were placed above the withers and the sternum for 5 s. Cardiac arrest and an isoelectric EEG were induced within 3 min after the onset of the electrical flow through the chest. The most obvious indicator of effective stunning and electrocution was termination of rhythmic breathing. Piglets with cardiac arrest showed only single gasps lasting up to 3 min after electrocution.

Conclusions

The evaluated stunning and electrocution protocol might ease concerns about timely piglet euthanasia. However, this should be verified in non-viable piglets to exclude influencing factors like dehydration and diseases.
The use of pasung for people with mental illness: a systematic review and narrative synthesis
Authors: Hidayat Muhamad Taufik , Lawn Sharon , Muir-Cochrane Eimear , Oster Candice
Published: December 2020

Background

Pasung is the term used in Indonesia and a number of other countries for seclusion and restraint of people with mental illness in the community, usually at home by their family. While pasung has been banned because it is contrary to human rights, its practice continues to exist within the community, particularly where community mental health services are limited, and in the absence of adequate social support, and pervasive negatives beliefs about mental illness. It is essential to understand the reasons for the ongoing use of pasung and to examine potential solutions.

Methods

A systematic review and narrative synthesis of peer-reviewed international literature was conducted to identify the socio-cultural contexts for pasung use, and interventions to address it. The analysis draws on the socio-ecological framework, which focused on relationships between the individual and their environment.

Result

Fifty published articles were included in the review; all studies were conducted in Asia and Africa, with 32 undertaken in Indonesia. Most studies were qualitative (n = 21). Others included one case–control study, one cross-sectional study, and seven surveys; only four studies examined the application of an intervention, and each used a pre and post methodology. Of these, two studies tested psychoeducational interventions which aimed to overcome family burden due to pasung, and each suggested a community mental health approach. The remaining two studies evaluated the intervention of ‘unlocking’; one study used a community-based culturally sensitive approach, and the other used a community-based rehabilitation program. Reasons for pasung given by family appear to be as a last resort and in the absence of other supports to help them care for the person with severe mental illness.

Conclusion

The findings highlight that a mixture of individual, interpersonal, community and policy interventions are needed to reduce the use of pasung. While consumer and carer involvement as part of a socio-ecological approach is understood to be effective in reducing pasung, an understanding of how to elaborate this in the management of pasung remains elusive.

Review RegistrationCRD42020157543: CRD
Abnormally activated OPN/integrin αVβ3/FAK signalling is responsible for EGFR-TKI resistance in EGFR mutant non-small-cell lung cancer
Authors: Fu Yulong , Zhang Yang , Lei Zhe , Liu Ting , Cai Tingting , Wang Anqi , Du Wenwen , Zeng Yuanyuan , Zhu Jianjie , Liu Zeyi , Huang Jian-an
Published: December 2020

Background

Acquired epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance limits the long-term clinical efficacy of tyrosine kinase-targeting drugs. Although most of the mechanisms of acquired EGFR-TKI resistance have been revealed, the mechanism of ~ 15% of cases has not yet been elucidated.

Methods

Cell viability was analysed using the Cell Counting Kit-8 (CCK-8) assay. Proteome profiler array analysis was performed to find proteins contributing to acquired EGFR-TKI resistance. Secreted OPN was detected by ELISA. Immunohistochemical analysis was conducted to detect expression of integrin αV in NSCLC tissue. The effect of VS-6063 on apoptosis and proliferation of PC9 gefitinib-resistant cells was detected by fluorescence-activated cell sorting (FACS) and clonogenic assays. A mouse xenograft model was used to assess the effect of VS-6063 on the sensitivity of PC9 gefitinib-resistant cells to gefitinib.

Results

OPN was overexpressed in acquired EGFR-TKI-resistant NSCLCs. Secreted OPN contributed to acquired EGFR-TKI resistance by activating the integrin αVβ3/FAK pathway. Inhibition of FAK signalling increased sensitivity to EGFR-TKIs in PC9 gefitinib-resistant cells both in vitro and in vivo.

Conclusions

OPN contributes to acquired EGFR-TKI resistance by up-regulating expression of integrin αVβ3, which activates the downstream FAK/AKT and ERK signalling pathways to promote cell proliferation in NSCLC.
Proteomic signatures of 16 major types of human cancer reveal universal and cancer-type-specific proteins for the identification of potential therapeutic targets
Authors: Zhou Yangying , Lih T. Mamie , Pan Jianbo , Höti Naseruddin , Dong Mingming , Cao Liwei , Hu Yingwei , Cho Kyung-Cho , Chen Shao-Yung , Eguez Rodrigo Vargas , Gabrielson Edward , Chan Daniel W. , Zhang Hui , Li Qing Kay
Published: December 2020

Background

Proteomic characterization of cancers is essential for a comprehensive understanding of key molecular aberrations. However, proteomic profiling of a large cohort of cancer tissues is often limited by the conventional approaches.

Methods

We present a proteomic landscape of 16 major types of human cancer, based on the analysis of 126 treatment-naïve primary tumor tissues, 94 tumor-matched normal adjacent tissues, and 12 normal tissues, using mass spectrometry-based data-independent acquisition approach.

Results

In our study, a total of 8527 proteins were mapped to brain, head and neck, breast, lung (both small cell and non-small cell lung cancers), esophagus, stomach, pancreas, liver, colon, kidney, bladder, prostate, uterus and ovary cancers, including 2458 tissue-enriched proteins. Our DIA-based proteomic approach has characterized major human cancers and identified universally expressed proteins as well as tissue-type-specific and cancer-type-specific proteins. In addition, 1139 therapeutic targetable proteins and 21 cancer/testis (CT) antigens were observed.

Conclusions

Our discoveries not only advance our understanding of human cancers, but also have implications for the design of future large-scale cancer proteomic studies to assist the development of diagnostic and/or therapeutic targets in multiple cancers.
Transesophageal echocardiography-associated tracheal microaspiration and ventilator-associated pneumonia in intubated critically ill patients: a multicenter prospective observational study
Authors: Bagate François , Rouzé Anahita , Zerimech Farid , Boissier Florence , Labbe Vincent , Razazi Keyvan , Carteaux Guillaume , de Prost Nicolas , Balduyck Malika , Maboudou Patrice , Nseir Saad , Mekontso Dessap Armand
Published: December 2020

Background

Microaspiration of gastric and oropharyngeal secretions is the main causative mechanism of ventilator-associated pneumonia (VAP). Transesophageal echocardiography (TEE) is a routine investigation tool in intensive care unit and could enhance microaspiration. This study aimed at evaluating the impact of TEE on microaspiration and VAP in intubated critically ill adult patients.

Methods

It is a four-center prospective observational study. Microaspiration biomarkers (pepsin and salivary amylase) concentrations were quantitatively measured on tracheal aspirates drawn before and after TEE. The primary endpoint was the percentage of patients with TEE-associated microaspiration, defined as: (1) ≥ 50% increase in biomarker concentration between pre-TEE and post-TEE samples, and (2) a significant post-TEE biomarker concentration (> 200 μg/L for pepsin and/or > 1685 IU/L for salivary amylase). Secondary endpoints included the development of VAP within three days after TEE and the evolution of tracheal cuff pressure throughout TEE.

Results

We enrolled 100 patients (35 females), with a median age of 64 (53–72) years. Of the 74 patients analyzed for biomarkers, 17 (23%) got TEE-associated microaspiration. However, overall, pepsin and salivary amylase levels were not significantly different between before and after TEE, with wide interindividual variability. VAP occurred in 19 patients (19%) within 3 days following TEE. VAP patients had a larger tracheal tube size and endured more attempts of TEE probe introduction than their counterparts but showed similar aspiration biomarker concentrations. TEE induced an increase in tracheal cuff pressure, especially during insertion and removal of the probe.

Conclusions

We could not find any association between TEE-associated microaspiration and the development of VAP during the three days following TEE in intubated critically ill patients. However, our study cannot formally rule out a role for TEE because of the high rate of VAP observed after TEE and the limitations of our methods.
Peripheral blood transcriptomic sub-phenotypes of pediatric acute respiratory distress syndrome
Authors: Yehya Nadir , Varisco Brian M. , Thomas Neal J. , Wong Hector R. , Christie Jason D. , Feng Rui
Published: December 2020

Background

Acute respiratory distress syndrome (ARDS) is heterogeneous and may be amenable to sub-phenotyping to improve enrichment for trials. We aimed to identify subtypes of pediatric ARDS based on whole blood transcriptomics.

Methods

This was a prospective observational study of children with ARDS at the Children’s Hospital of Philadelphia (CHOP) between January 2018 and June 2019. We collected blood within 24 h of ARDS onset, generated expression profiles, and performed k-means clustering to identify sub-phenotypes. We tested the association between sub-phenotypes and PICU mortality and ventilator-free days at 28 days using multivariable logistic and competing risk regression, respectively.

Results

We enrolled 106 subjects, of whom 96 had usable samples. We identified three sub-phenotypes, dubbed CHOP ARDS Transcriptomic Subtypes (CATS) 1, 2, and 3. CATS-1 subjects (n = 31) demonstrated persistent hypoxemia, had ten subjects (32%) with immunocompromising conditions, and 32% mortality. CATS-2 subjects (n = 29) had more immunocompromising diagnoses (48%), rapidly resolving hypoxemia, and 24% mortality. CATS-3 subjects (n = 36) had the fewest comorbidities and also had rapidly resolving hypoxemia and 8% mortality. The CATS-3 subtype was associated with lower mortality (OR 0.18, 95% CI 0.04–0.86) and higher probability of extubation (subdistribution HR 2.39, 95% CI 1.32–4.32), relative to CATS-1 after adjustment for confounders.

Conclusions

We identified three sub-phenotypes of pediatric ARDS using whole blood transcriptomics. The sub-phenotypes had divergent clinical characteristics and prognoses. Further studies should validate these findings and investigate mechanisms underlying differences between sub-phenotypes.
Postoperative hypotension in patients discharged to the intensive care unit after non-cardiac surgery is associated with adverse clinical outcomes
Authors: Smischney Nathan J. , Shaw Andrew D. , Stapelfeldt Wolf H. , Boero Isabel J. , Chen Qinyu , Stevens Mitali , Khanna Ashish K.
Published: December 2020

Background

The postoperative period is critical for a patient’s recovery, and postoperative hypotension, specifically, is associated with adverse clinical outcomes and significant harm to the patient. However, little is known about the association between postoperative hypotension in patients in the intensive care unit (ICU) after non-cardiac surgery, and morbidity and mortality, specifically among patients who did not experience intraoperative hypotension. The goal of this study was to assess the impact of postoperative hypotension at various absolute hemodynamic thresholds (≤ 75, ≤ 65 and ≤ 55 mmHg), in the absence of intraoperative hypotension (≤ 65 mmHg), on outcomes among patients in the ICU following non-cardiac surgery.

Methods

This multi-center retrospective cohort study included specific patient procedures from Optum® healthcare database for patients without intraoperative hypotension (MAP ≤ 65 mmHg) discharged to the ICU for ≥ 48 h after non-cardiac surgery with valid mean arterial pressure (MAP) readings. A total of 3185 procedures were included in the final cohort, and the association between postoperative hypotension and the primary outcome, 30-day major adverse cardiac or cerebrovascular events, was assessed. Secondary outcomes examined included all-cause 30- and 90-day mortality, 30-day acute myocardial infarction, 30-day acute ischemic stroke, 7-day acute kidney injury stage II/III and 7-day continuous renal replacement therapy/dialysis.

Results

Postoperative hypotension in the ICU was associated with an increased risk of 30-day major adverse cardiac or cerebrovascular events at MAP ≤ 65 mmHg (hazard ratio [HR] 1.52; 98.4% confidence interval [CI] 1.17–1.96) and ≤ 55 mmHg (HR 2.02, 98.4% CI 1.50–2.72). Mean arterial pressures of ≤ 65 mmHg and ≤ 55 mmHg were also associated with higher 30-day mortality (MAP ≤ 65 mmHg, [HR 1.56, 98.4% CI 1.22–2.00]; MAP ≤ 55 mmHg, [HR 1.97, 98.4% CI 1.48–2.60]) and 90-day mortality (MAP ≤ 65 mmHg, [HR 1.49, 98.4% CI 1.20–1.87]; MAP ≤ 55 mmHg, [HR 1.78, 98.4% CI 1.38–2.31]). Furthermore, we found an association between postoperative hypotension with MAP ≤ 55 mmHg and acute kidney injury stage II/III (HR 1.68, 98.4% CI 1.02–2.77). No associations were seen between postoperative hypotension and 30-day readmissions, 30-day acute myocardial infarction, 30-day acute ischemic stroke and 7-day continuous renal replacement therapy/dialysis for any MAP threshold.

Conclusions

Postoperative hypotension in critical care patients with MAP ≤ 65 mmHg is associated with adverse events even without experiencing intraoperative hypotension.
Role of extracorporeal membrane oxygenation in children with sepsis: a systematic review and meta-analysis
Authors: Ramanathan Kollengode , Yeo Nicholas , Alexander Peta , Raman Lakshmi , Barbaro Ryan , Tan Chuen Seng , Schlapbach Luregn J. , MacLaren Graeme
Published: December 2020

Background

The benefits of extracorporeal membrane oxygenation (ECMO) in children with sepsis remain controversial. Current guidelines on management of septic shock in children recommend consideration of ECMO as salvage therapy. We sought to review peer-reviewed publications on effectiveness of ECMO in children with sepsis.

Methods

Studies reporting on mortality in children with sepsis supported with ECMO, published in PubMed, Scopus and Embase from 1972 till February 2020, were included in the review. This study was done in adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis statement after registering the review protocol with PROSPERO. Study eligibility was independently assessed by two authors and disagreements resolved by a third author. Publications were reviewed for quality using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Random-effects meta-analyses (DerSimonian and Laird) were conducted, and 95% confidence intervals were computed using the Clopper-Pearson method. Outliers were identified by the Baujat plot and leave-one-out analysis if there was considerable heterogeneity. The primary outcome measure was survival to discharge. Secondary outcome measures included hospital length of stay, subgroup analysis of neonatal and paediatric groups, types and duration of ECMO and complications .

Results

Of the 2054 articles screened, we identified 23 original articles for systematic review and meta-analysis. Cumulative estimate of survival (13 studies, 2559 patients) in the cohort was 59% (95%CI: 51–67%). Patients had a median length of hospital stay of 28.8 days, median intensive care unit stay of 13.5 days, and median ECMO duration of 129 h. Children needing venoarterial ECMO (9 studies, 208 patients) showed overall pooled survival of 65% (95%CI: 50–80%). Neonates (< 4 weeks of age) with sepsis needing ECMO (7 studies, 85 neonates) had pooled survival of 73% (95%CI: 56- 87%). Gram positive organisms were the most common pathogens (47%) in septic children supported with ECMO.

Conclusion

Survival rates of children with sepsis needing ECMO was 59%. Neonates had higher survival rates (73%); gram positive organisms accounted for most common infections in children needing ECMO. Despite limitations, pooled survival data from this review indicates consideration of ECMO in refractory septic shock for all pediatric age groups.
Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs
Authors: He Shuai , Wang Lin-He , Liu Yang , Li Yi-Qi , Chen Hai-Tian , Xu Jing-Hong , Peng Wan , Lin Guo-Wang , Wei Pan-Pan , Li Bo , Xia Xiaojun , Wang Dan , Bei Jin-Xin , He Xiaoshun , Guo Zhiyong
Published: December 2020

Background

As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing.

Results

We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novelCOCH+fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors, and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues.

Conclusions

The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.
Mentalization for Offending Adult Males (MOAM): study protocol for a randomized controlled trial to evaluate mentalization-based treatment for antisocial personality disorder in male offenders on community probation
Authors: Fonagy Peter , Yakeley Jessica , Gardner Tessa , Simes Elizabeth , McMurran Mary , Moran Paul , Crawford Mike , Frater Alison , Barrett Barbara , Cameron Angus , Wason James , Pilling Stephen , Butler Stephen , Bateman Anthony
Published: December 2020

Background

Antisocial personality disorder (ASPD), although associated with very significant health and social burden, is an under-researched mental disorder for which clinically effective and cost-effective treatment methods are urgently needed. No intervention has been established for prevention or as the treatment of choice for this disorder. Mentalization-based treatment (MBT) is a psychotherapeutic treatment that has shown some promising preliminary results for reducing personality disorder symptomatology by specifically targeting the ability to recognize and understand the mental states of oneself and others, an ability that is compromised in people with ASPD. This paper describes the protocol of a multi-site RCT designed to test the effectiveness and cost-effectiveness of MBT for reducing aggression and alleviating the wider symptoms of ASPD in male offenders subject to probation supervision who fulfil diagnostic criteria for ASPD.

Methods

Three hundred and two participants recruited from a pool of offenders subject to statutory supervision by the National Probation Service at 13 sites across the UK will be randomized on a 1:1 basis to 12 months of probation plus MBT or standard probation as usual, with follow-up to 24 months post-randomization. The primary outcome is frequency of aggressive antisocial behaviour as assessed by the Overt Aggression Scale – Modified. Secondary outcomes include violence, offending rates, alcohol use, drug use, mental health status, quality of life, and total service use costs. Data will be gathered from police and criminal justice databases, NHS record linkage, and interviews and self-report measures administered to participants. Primary analysis will be on an intent-to-treat basis; per-protocol analysis will be undertaken as secondary analysis. The primary outcome will be analysed using hierarchical mixed-effects linear regression. Secondary outcomes will be analysed using mixed-effects linear regression, mixed-effects logistic regression, and mixed-effects Poisson models for secondary outcomes depending on whether the outcome is continuous, binary, or count data. A cost-effectiveness and cost-utility analysis will be undertaken.

Discussion

This definitive, national, multi-site trial is of sufficient size to evaluate MBT to inform policymakers, service commissioners, clinicians, and service users about its potential to treat offenders with ASPD and the likely impact on the population at risk.

Trial registration

ISRCTN 32309003. Registered on 8 April 2016.
Identification of a cytosine methyltransferase that improves transformation efficiency in Methylomonas sp. DH-1
Authors: Ren Jun , Lee Hyang-Mi , Thai Thi Duc , Na Dokyun
Published: December 2020

Background

Industrial biofuels and other value-added products can be produced from metabolically engineered microorganisms. Methylomonas sp. DH-1 is a candidate platform for bioconversion that uses methane as a carbon source. Although several genetic engineering techniques have been developed to work with Methylomonas sp. DH-1, the genetic manipulation of plasmids remains difficult because of the restriction-modification (RM) system present in the bacteria. Therefore, the RM system in Methylomonas sp. DH-1 must be identified to improve the genetic engineering prospects of this microorganism.

Results

We identified a DNA methylation site, TGGCCA, and its corresponding cytosine methyltransferase for the first time in Methylomonas sp. DH-1 through whole-genome bisulfite sequencing. The methyltransferase was confirmed to methylate the fourth nucleotide of TGGCCA. In general, methylated plasmids exhibited better transformation efficiency under the protection of the RM system than non-methylated plasmids did. As expected, when we transformed Methylomonas sp. DH-1 with plasmid DNA harboring the psy gene, the metabolic flux towards carotenoid increased. The methyltransferase-treated plasmid exhibited an increase in transformation efficiency of 2.5 × 103 CFU/μg (124%). The introduced gene increased the production of carotenoid by 26%. In addition, the methyltransferase-treated plasmid harboring anti-psy sRNA gene exhibited an increase in transformation efficiency by 70% as well. The production of carotenoid was decreased by 40% when the psy gene was translationally repressed by anti-psy sRNA.

Conclusions

Plasmid DNA methylated by the discovered cytosine methyltransferase from Methylomonas sp. DH-1 had a higher transformation efficiency than non-treated plasmid DNA. The RM system identified in this study may facilitate the plasmid-based genetic manipulation of methanotrophs.
Genetic diversity and characteristics of high-level tigecycline resistance Tet(X) in Acinetobacter species
Authors: Chen Chong , Cui Chao-Yue , Yu Jun-Jun , He Qian , Wu Xiao-Ting , He Yu-Zhang , Cui Ze-Hua , Li Cang , Jia Qiu-Lin , Shen Xiang-Guang , Sun Ruan-Yang , Wang Xi-Ran , Wang Min-Ge , Tang Tian , Zhang Yan , Liao Xiao-Ping , Kreiswirth Barry N. , Zhou Shi-Dan , Huang Bin , Du Hong , Sun Jian , Chen Liang , Liu Ya-Hong
Published: December 2020

Background

The recent emergence and dissemination of high-level mobile tigecycline resistance Tet(X) challenge the clinical effectiveness of tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens. Although tet(X) has been found in various bacterial species, less is known about phylogeographic distribution and phenotypic variance of different genetic variants.

Methods

Herein, we conducted a multiregional whole-genome sequencing study of tet(X)-positive Acinetobacter isolates from human, animal, and their surrounding environmental sources in China. The molecular and enzymatic features of tet(X) variants were characterized by clonal expression, microbial degradation, reverse transcription, and gene transfer experiments, while the tet(X) genetic diversity and molecular evolution were explored by comparative genomic and Bayesian evolutionary analyses.

Results

We identified 193 tet(X)-positive isolates from 3846 samples, with the prevalence ranging from 2.3 to 25.3% in nine provinces in China. The tet(X) was broadly distributed in 12 Acinetobacter species, including six novel species firstly described here. Besides tet(X3) (n = 188) and tet(X4) (n = 5), two tet(X5) variants, tet(X5.2) (n = 36) and tet(X5.3) (n = 4), were also found together with tet(X3) or tet(X4) but without additive effects on tetracyclines. These tet(X)-positive Acinetobacter spp. isolates exhibited 100% resistance rates to tigecycline and tetracycline, as well as high minimum inhibitory concentrations to eravacycline (2–8 μg/mL) and omadacycline (8–16 μg/mL). Genetic analysis revealed that different tet(X) variants shared an analogous ISCR2-mediated transposon structure. The molecular evolutionary analysis indicated that Tet(X) variants likely shared the same common ancestor with the chromosomal monooxygenases that are found in environmental Flavobacteriaceae bacteria, but sequence divergence suggested separation ~ 9900 years ago (7887 BC), presumably associated with the mobilization of tet(X)-like genes through horizontal transfer.

Conclusions

Four tet(X) variants were identified in this study, and they were widely distributed in multiple Acinetobacter spp. strains from various ecological niches across China. Our research also highlighted the crucial role of ISCR2 in mobilizing tet(X)-like genes between different Acinetobacter species and explored the evolutionary history of Tet(X)-like monooxygenases. Further studies are needed to evaluate the clinical impact of these mobile tigecycline resistance genes.
Seroprevalence and associated risk factors of Toxoplasma gondii infection in patients undergoing hemodialysis and healthy group
Authors: Soltani Shahrzad , Kahvaz Mehdi Sagha , Soltani Sheyda , Maghsoudi Fatemeh , Foroutan Masoud
Published: December 2020

Objectives

In this study, the seroprevalence of anti-Toxoplasma gondii(T. gondii) specific antibodies in patients undergoing hemodialysis compared to the control group were evaluated. In this case–control study, 200 hemodialysis patients (HDP) and 100 healthy controls were participated. The specific antibodies (IgG/IgM) in both groups were tested using enzyme-linked immunosorbent assay (ELISA) method. A structured questionnaire containing some demographic information was completed for each person in case and control groups.

Results

The overall seroprevalence ofT. gondiiinfection was 49.5% (99/200) and 23.0% (23/100) in the case and control groups, respectively. There was a significant association between seroprevalence ofT. gondiiinfection and contact with cats (P < 0.001), consumption of raw/undercooked meat (P = 0.01), and source of drinking water (P = 0.001) in the hemodialysis patients. Also, in the control subjects, there were a significant association between consumption of raw/undercooked meat (P = 0.04) and source of drinking water (P = 0.001) withT. gondiiinfection. The findings showed a high seroprevalence ofT. gondiiinfection in HDP compared with healthy controls; thus, we recommend the regular screening programs forT. gondiiinfection in this susceptible group.
Alpha connectivity and inhibitory control in adults with autism spectrum disorder
Authors: Yuk Veronica , Dunkley Benjamin T. , Anagnostou Evdokia , Taylor Margot J.
Published: December 2020

Background

Individuals with autism spectrum disorder (ASD) often report difficulties with inhibition in everyday life. During inhibition tasks, adults with ASD show reduced activation of and connectivity between brain areas implicated in inhibition, suggesting impairments in inhibitory control at the neural level. Our study further investigated these differences by using magnetoencephalography (MEG) to examine the frequency band(s) in which functional connectivity underlying response inhibition occurs, as brain functions are frequency specific, and whether connectivity in certain frequency bands differs between adults with and without ASD.

Methods

We analysed MEG data from 40 adults with ASD (27 males; 26.94 ± 6.08 years old) and 39 control adults (27 males; 27.29 ± 5.94 years old) who performed a Go/No-go task. The task involved two blocks with different proportions of No-go trials: Inhibition (25% No-go) and Vigilance (75% No-go). We compared whole-brain connectivity in the two groups during correct No-go trials in the Inhibition vs. Vigilance blocks between 0 and 400 ms.

Results

Despite comparable performance on the Go/No-go task, adults with ASD showed reduced connectivity compared to controls in the alpha band (8–14 Hz) in a network with a main hub in the right inferior frontal gyrus. Decreased connectivity in this network predicted more self-reported difficulties on a measure of inhibition in everyday life.

Limitations

Measures of everyday inhibitory control were not available for all participants, so this relationship between reduced network connectivity and inhibitory control abilities may not be necessarily representative of all adults with ASD or the larger ASD population. Further research with independent samples of adults with ASD, including those with a wider range of cognitive abilities, would be valuable.

Conclusions

Our findings demonstrate reduced functional brain connectivity during response inhibition in adults with ASD. As alpha-band synchrony has been linked to top-down control mechanisms, we propose that the lack of alpha synchrony observed in our ASD group may reflect difficulties in suppressing task-irrelevant information, interfering with inhibition in real-life situations.
Recurrent obstructive uropathy secondary to pyometrocolpos in an 8-month-old infant: a case report
Authors: Kiritta Richard , Balyorugulu Georgina , Ahmed Maimuna , Christopher Frank , Miltenburg Andrea Solnes , Kihunrwa Albert
Published: December 2020

Background

Pyometrocolpos is accumulation of infected fluid in the uterus and vagina. It is rare in children, mostly seen after menarche as a result of obstructive congenital genital malformation that impairs free drainage of the uterine secretions. In a child, it may present as an acute illness that necessitates urgent and appropriate management and treatment of the underlying cause, which can be a challenge in a resource-limited setting.

Case presentation

We report a case of pyometrocolpos in an 8-month-old African infant who presented with fever, vomiting, decreased urine output, and abdominal distension of 12 days’ duration. An abdominal examination revealed a subumbilical midline incision scar and a midline lower abdominal mass. She appeared to have presented at the emergency department with similar complaints 2 months earlier and had been diagnosed with pyometra, which was managed by emergency laparotomy for pus drainage, and she was kept on antibiotics. Recovery was established after 10 days of admission, and the patient was discharged to home. Her symptoms reappeared 2 months after the first presentation. Her blood work showed significant leukocytosis with neutrophilia, and abdominal ultrasound depicted bilateral hydronephrosis with hydroureters and a fluid-filled uterus. Examination under anesthesia in the operating theater revealed normal-looking female genitalia with a cribriform hymen, beneath which lied a transverse vaginal septum. Foul-smelling pus was aspirated through the septum, and septectomy was performed to allow 350 ml of pus to drain. A pus sample was sent for culture and sensitivity, and Escherichia coli sensitive to ceftriaxone and gentamicin was isolated.

Conclusion

Pyometrocolpos is rare in childhood but should be suspected in a girl presenting with a midline lower abdominal mass accompanied with urinary obstructive symptoms associated with fever and gastrointestinal symptoms. Escherichia coli seems to be the most probable offending organism, but pus culture is crucial for antibiotic stewardship in proper management of the infection. Definitive treatment should focus on correcting the obstructive anatomical congenital deformity that caused the obstruction in order to avoid recurrence.
The role of prognostic nutritional index in the management of pulmonary sarcomatoid carcinoma
Authors: Wang Yan , Cao Yu , Liu Junfeng
Published: December 2020

Background

Pulmonary sarcomatoid carcinoma is characterized by poor survival rates compared with other non-small cell lung cancer. Prognostic nutritional index has significant prognostic value in many malignant tumors. We conducted this retrospective study to investigate the role of prognostic nutritional index in patients with pulmonary sarcomatoid carcinoma and to determine prognostic factors.

Methods

Of 8176 patients with resected lung cancer in a single high-volume institution between 2008 and 2015, 91 patients with pathologically diagnosed sarcomatoid carcinoma were included in our study and evaluated. Kaplan–Meier analysis and Cox regression analysis were conducted to analyze clinicopathologic data. Subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) among pulmonary sarcomatoid carcinoma patients were also conducted.

Results

Univariable analysis showed that tumor size (P = 0.018 in OS), and P = 0.021 in RFS), tumor stage(P < 0.001 in OS, and P = 0.002 in RFS), nodal metastasis (P < 0.001 in OS, and P < 0.001 in RFS), pathological stage (P < 0.001 in OS, and P < 0.001 in RFS), treatment modality (P = 0.032 in OS, and P = 0.059 in RFS) and PNI (P < 0.001 in OS, and P < 0.001 in RFS), were significant factors of both OS and RFS. In multivariable analysis, for OS, the pathological stage (Hazard ratio (HR) 1.432; 95% confidence interval (95% CI) 1.210–1.695; P < 0.001) and PNI (HR 0.812; 95% CI 0.761–0.865; P < 0.001) were independent prognostic factors. And for RFS, We found PNI as an independent prognostic factor (HR 0.792; 95% CI 0.739–0.848; P < 0.001), and the pathological stage (HR 1.373; 95% CI 1.160–1.625; P < 0.001). In the subgroup of patients with PNI ≥ 49.4, univariable analysis showed treatment modality was a significant factor of overall survival (P = 0.001); multivariable analysis showed patients received postoperative chemotherapy (HR 0.288; 95% CI 0.095–0.874; P = 0.028) or postoperative chemotherapy with targeted therapy (HR 0.148; 95% CI 0.030–0.726; P = 0.019) has better overall survival rates.

Conclusion

The PNI and the pathological TNM stage are independent prognostic factors for pulmonary sarcomatoid carcinoma. PNI is an important indicator for the selection of postoperative adjuvant therapy. Patients with PNI ≥ 49.4 may benefit from postoperative chemotherapy and targeted therapy. We still need further prospective studies to confirm these results.
FLT3 inhibitors in acute myeloid leukaemia: assessment of clinical effectiveness, adverse events and future research—a systematic review and meta-analysis
Authors: Majothi S. , Adams D. , Loke J. , Stevens S. P. , Wheatley K. , Wilson J. S.
Published: December 2020

Background

FMS-like tyrosine kinase 3 (FLT3) is the most frequent mutation in AML. With two FLT3 inhibitors recently approved by the FDA (midostaurin and gilteritinib), there is a need to evaluate these targeted agents.

Purpose

To assess the clinical effectiveness of FLT3 inhibitors in AML patients.

Methods

Standard systematic review methods were utilised. Searches were conducted to July 2020 for completed and in-progress randomised controlled trials of FLT3 inhibitors in AML. A fixed-effect meta-analysis was undertaken.

Results

Eight completed trials involving 2656 patients and assessing five different FLT3 inhibitors (sorafenib, lestaurtinib, midostaurin, gilteritinib and quizartinib) were included. The pooled results were as follows (FLT3 inhibitor/control): overall survival hazard ratio (HR) = 0.83 (95% confidence interval [CI] 0.75 to 0.92, p = 0.0005), event-free survival HR = 0.85 (95% CI 0.77 to 0.94, p = 0.002), relapse-free survival HR = 0.76 (95% CI 0.64 to 0.90, p = 0.001), complete remission relative risk (RR) = 1.11 (95% CI 1.00 to 1.22. p = 0.05) and 60-day mortality RR = 1.04 (95% CI 0.77 to 1.40, p = 0.79).

Relative risk of grade 3 and above vascular, dermatological, respiratory and hepatobiliary adverse events were found to be statistically significantly higher in the FLT3 inhibitor group compared to control, but the actual numbers of events were relatively small. Nineteen ongoing trials are still in progress, only one of which specifically targets older patients with AML.

Conclusions

There is evidence to support the use of FLT3 inhibitors in patients with AML, but more data is needed to verify the optimum use of the drugs regarding type of inhibitor, disease stage and patient characteristics, not only in relation to disease control, but adverse events and quality of life. There are a large number of ongoing trials; therefore, the results of this review are not a fait accompli; thus, is it recommended that the review be updated in a couple of years’ time. Given the challenges in extracting the complete data set required to assess clinical effectiveness, it is highly recommended that ongoing and future trials improve transparency and consistency of reporting of all trial outcomes, particularly disease control and adverse events, to enable a global clinical effectiveness assessment.

Systematic review registration

PROSPERO CRD42017055581
Mindfulness-based interventions for children and adolescents across all settings: a scoping review protocol
Authors: Perrier Marie-France , Gurgel-Juarez Nalia , Flowers Heather Leslie , McCormick Anna , Short Sarah J.
Published: December 2020

Background and purpose

Although mindfulness-based interventions (MBIs) are becoming increasingly popular, the application of MBIs with children and adolescents is still in its infancy. Mapping the existing literature is necessary to help guide pediatric mindfulness interventions. Our purpose is to synthesize the evidence of reported MBIs for children and adolescents with and without physical, mental, and cognitive disorders. Accordingly, we aim to identify trends and gaps in the literature, so that we can provide direction to researchers who seek to advance the evidence base for using MBIs in pediatric populations.

Methods

Our search strategy will be conducted following Arksey and O’Malley’s methodological framework. It will include a comprehensive search of published studies in 7 databases, gray literature, conference proceedings, and citations of selected articles. Two independent reviewers will evaluate all abstracts and full articles that have a pediatric sample (children 2–17 years), use MBIs to promote development or to remediate underlying disorders, and are written in English or French. We will identify the definitions and concepts from MBIs, categorize accepted studies according to etiology and rehabilitation type, describe intervention methodology, and report outcomes of selected studies.

Discussion

Our review will provide a comprehensive overview of the pediatric mindfulness intervention literature to date, involving a range of mental, cognitive, and physical outcomes for healthy children and adolescents and for those with a variety of disorders in clinical and institutional settings. We will disseminate results to mindfulness practitioners and provide guidance to future pediatric researchers in their development and application of mindfulness interventions, thereby contributing to the scientific understanding of mindfulness for the ultimate betterment of child and adolescent well-being and life-long functioning.

Systematic review registration

PROSPERO does not accept scoping review protocols.