bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring a novel method for optimising the implementation of a colorectal cancer risk prediction tool into primary care: a qualitative study
Authors: Milton Shakira , Emery Jon D. , Rinaldi Jane , Kinder Joanne , Bickerstaffe Adrian , Saya Sibel , Jenkins Mark A. , McIntosh Jennifer
Published: May 2022

Background

We developed a colorectal cancer risk prediction tool (‘CRISP’) to provide individualised risk-based advice for colorectal cancer screening. Using known environmental, behavioural, and familial risk factors, CRISP was designed to facilitate tailored screening advice to patients aged 50 to 74 years in general practice. In parallel to a randomised controlled trial of the CRISP tool, we developed and evaluated an evidence-based implementation strategy.

Methods

Qualitative methods were used to explore the implementation of CRISP in general practice. Using one general practice in regional Victoria, Australia, as a ‘laboratory’, we tested ways to embed CRISP into routine clinical practice. General practitioners, nurses, and operations manager co-designed the implementation methods with researchers, focussing on existing practice processes that would be sustainable. Researchers interviewed the staff regularly to assess the successfulness of the strategies employed, and implementation methods were adapted throughout the study period in response to feedback from qualitative interviews.

The Consolidated Framework for Implementation Research (CFIR) underpinned the development of the interview guide and intervention strategy. Coding was inductive and themes were developed through consensus between the authors. Emerging themes were mapped onto the CFIR domains and a fidelity checklist was developed to ensure CRISP was being used as intended.

Results

Between December 2016 and September 2019, 1 interviews were conducted, both face-to-face and via videoconferencing (Zoom). All interviews were transcribed verbatim and coded. Themes were mapped onto the following CFIR domains: (1) ‘characteristics of the intervention’: CRISP was valued but time consuming; (2) ‘inner setting’: the practice was open to changing systems; 3. ‘outer setting’: CRISP helped facilitate screening; (4) ‘individual characteristics’: the practice staff were adaptable and able to facilitate adoption of new clinical processes; and (5) ‘processes’: fidelity checking, and education was important.

Conclusions

These results describe a novel method for exploring implementation strategies for a colorectal cancer risk prediction tool in the context of a parallel RCT testing clinical efficacy. The study identified successful and unsuccessful implementation strategies using an adaptive methodology over time. This method emphasised the importance of co-design input to make an intervention like CRISP sustainable for use in other practices and with other risk tools.
Protective ileostomy increased the incidence of rectal stenosis after anterior resection for rectal cancer
Authors: Zhang Hui , Li Shanshan , Jin Xin , Wu Xian , Zhang Zhiyuan , Shen Lijun , Wan Juefeng , Wang Yan , Wang Yaqi , Yang Wang , Zhou Menglong , Zhang Jing , Lv Tao , Deng Yun , Xia Fan , Zhang Zhen
Published: May 2022

Background

In most of the views, rectal stenosis after anterior resection for rectal cancer results from pelvic radiotherapy. However, patients without receiving radiotherapy also suffer stenosis. In this study, we evaluated the factors associated with rectal stenosis after anterior rectal resection (ARR).

Methods

We conducted a retrospective study with ARR patients who underwent neoadjuvant chemoradiotherapy and the patients without radiotherapy. Patients who received watch and wait strategy with a clinical complete response after chemoradiotherapy were also included. Patients with colonoscopy follow-up were included for further analyses; 439 patients who underwent neoadjuvant chemoradiotherapy; 545 patients who received ARR without radiotherapy and 33 patients who received watch and wait strategy. Stenosis was diagnosed when a 12-mm diameter colonoscopy could not be passed through the rectum. Univariate and multivariate logistic regression analyses were performed to identify variables associated with rectal stenosis.

Results

According to the multivariate analysis in patients receiving ARR, both protective stoma and preoperative radiotherapy affected the occurrence of stenosis, with the odds ratios (ORs) of 3.375 and 2.251, respectively. According to the multivariate analysis, a preventive ileostomy was the only factor associated with stenosis both in patients receiving preoperative radiotherapy and without radiotherapy. Non-reversal ileostomy and long time between ileostomy and restoration increased the possibility of stenosis. In 33 patients who received watch and wait strategy, only one patient (3%) experienced stenosis.

Conclusion

Both surgery and radiotherapy are risk factors for rectal stenosis in rectal cancer patients. Compared to preoperative radiotherapy, a protective ileostomy is a more critical factor associated with rectal stenosis.
Resection and reconstruction of huge tumors in the chest wall
Authors: Dai Zhibing , Maihemuti Maierdanjiang , Sun Yachao , Jiang Renbing
Published: May 2022

Objective

To evaluate the experience and effects of resection and reconstruction of 4 cases of huge tumors in the chest wall.

Methods

The clinical data of 4 patients with huge tumors in the chest wall from July 2015 to January 2020 were collected and analyzed. There were 2 males and 2 females.Chondrosarcoma was diagnosed in 2 cases, giant cell tumor was diagnosed in 1 case,and metastasis from breast cancer was diagnosed in 1 case.All patients underwent extensive tumor resection and had thoracic exposure after tumor resection.Two patients underwent reconstruction with mesh and titanium mesh, and the incision was closed directly.The third patient underwent reconstruction with mesh and latissimus dorsi flap,and the fourth patient underwent reconstruction with mesh,titanium mesh and latissimus dorsi flap.

Result

One patient had incision infection after operation,which resolved after debridement.All patients were followed up for 2–6 years, no tumor recurrence or metastasis was noted during follow-up.None of patients had abnormal breathing, dyspnea or other physical discomfort.

Conclusion

It is difficult to resect the huge tumors in the chest wall,and it is more reasonable and safer to choose a reconstruction method using mesh and titanium mesh.The latissimus dorsi flap can achieve good results in repairing soft tissue defects.Close perioperative management and multidisciplinary team discussions can help to achieve better curative effects.
Dilated cardiomyopathy as the initial presentation of Becker muscular dystrophy: a systematic review of published cases
Authors: Del Rio-Pertuz Gaspar , Morataya Cristina , Parmar Kanak , Dubay Sarah , Argueta-Sosa Erwin
Published: May 2022

There are scarce publications regarding the presentation and outcome of Becker muscular dystrophy in adulthood when idiopathic dilated cardiomyopathy is the initial disease manifestation. We performed a systematic review using Medline, Embase, Cochrane, and Scopus to identify cases of adults with idiopathic dilated cardiomyopathy who were subsequently diagnosed with Becker muscular dystrophy from inception through August 2020. Six cases were found. We identified young males (Median age: 26 years) with Becker muscular dystrophy who first presented with dilated cardiomyopathy. Most patients initially presented with congestive heart failure symptoms (5/6, 83%), and had a median left ventricular ejection fraction of 23%. One case did have calf pseudohypertrophy. Musculoskeletal symptoms later appeared one to six years after the initial dilated cardiomyopathy presentation. Heart transplantation was the most common management strategy (4/6, 67%). A left ventricular assist device was used in one case as a bridge to heart transplant. Dilated cardiomyopathy can be the initial presentation of Becker muscular dystrophy in the third to fourth decades of life in adult patients, and musculoskeletal symptoms can be subclinical.
Psychological distress and social support among conflict refugees in urban, semi-rural and rural settlements in Uganda: burden and associations
Authors: Seruwagi Gloria , Nakidde Catherine , Lugada Eric , Ssematiko Maria , Ddamulira Dunstan P. , Masaba Andrew , Luswata Brian , Ochen Eric A. , Okot Betty , Muhangi Denis , Lawoko Stephen
Published: May 2022

Background

Recent research shows that psychological distress is on the rise globally as a result of the COVID-19 pandemic and restrictions imposed on populations to manage it. We studied the association between psychological distress and social support among conflict refugees in urban, semi-rural and rural settlements in Uganda during the COVID-19 pandemic.

Methods

Cross-sectional survey data on psychological distress, social support, demographics, socio-economic and behavioral variables was gathered from 1014 adult refugees randomly sampled from urban, semi-rural and rural refugee settlements in Uganda, using two-staged cluster sampling. Data was analyzed in SPSS-version 22, and statistical significance was assumed at p < 0.05.

Results

Refugees resident in rural/semi-rural settlements exhibited higher levels of psychological distress [F(2, 1011) = 47.91; p < 0.001], higher availability of social interaction [F(2, 1011) = 82.24; p < 0.001], lower adequacy of social interaction [F(2, 1011) = 54.11; p < 0.001], higher availability of social attachment [F(2, 1011) = 47.95; p < 0.001], and lower adequacy of social attachment [F(2, 1011) = 50.54; p < 0.001] than peers in urban settlements. Adequacy of social interaction significantly explained variations in psychological distress levels overall and consistently across settlements, after controlling for plausible confounders. Additionally, adequacy of social attachment significantly explained variations in psychological distress levels among refugees in rural settlements, after controlling for plausible confounders.

Conclusion

There is a settlement-inequality (i.e. rural vs. urban) in psychological distress and social support among conflict refugees in Uganda. To address psychological distress, Mental Health and Psychosocial Support Services (MHPSS) should focus on strategies which strengthen the existing social networks among refugees. Variations in social support are a key predictor of distress which should guide tailored need-adapted interventions instead of duplicating similar and generic interventions across diverse refugee settlements.
GABPA-activated TGFBR2 transcription inhibits aggressiveness but is epigenetically erased by oncometabolites in renal cell carcinoma
Authors: Fang Zhiqing , Zhang Ning , Yuan Xiaotian , Xing Xiangling , Li Xiaofeng , Qin Xin , Liu Zhengfang , Neo Shiyong , Liu Cheng , Kong Feng , Björkholm Magnus , Fan Yidong , Xu Dawei
Published: May 2022

Background

The ETS transcription factor GABPA has long been thought of as an oncogenic factor and recently suggested as a target for cancer therapy due to its critical effect on telomerase activation, but the role of GABPA in clear cell renal cell carcinoma (ccRCC) is unclear. In addition, ccRCC is characterized by metabolic reprograming with aberrant accumulation of L-2-hydroxyglurate (L-2HG), an oncometabolite that has been shown to promote ccRCC development and progression by inducing DNA methylation, however, its downstream effectors remain poorly defined.

Methods

siRNAs and expression vectors were used to manipulate the expression of GABPA and other factors and to determine cellular/molecular and phenotypic alterations. RNA sequencing and ChIP assays were performed to identify GABPA target genes. A human ccRCC xenograft model in mice was used to evaluate the effect of GABPA overexpression on in vivo tumorigenesis and metastasis. ccRCC cells were incubated with L-2-HG to analyze GABPA expression and methylation. We carried out immunohistochemistry on patient specimens and TCGA dataset analyses to assess the effect of GABPA on ccRCC survival.

Results

GABPA depletion, although inhibiting telomerase expression, robustly enhanced proliferation, invasion and stemness of ccRCC cells, whereas GABPA overexpression exhibited opposite effects, strongly inhibiting in vivo metastasis and carcinogenesis. TGFBR2 was identified as the GABPA target gene through which GABPA governed the TGFβ signaling to dictate ccRCC phenotypes. GABPA and TGFBR2 phenocopies each other in ccRCC cells. Higher GABPA or TGFBR2 expression predicted longer survival in patients with ccRCC. Incubation of ccRCC cells with L-2-HG mimics GABPA-knockdown-mediated phenotypic alterations. L-2-HG silenced the expression of GABPA in ccRCC cells by increasing its methylation.

Conclusions

GABPA acts as a tumor suppressor by stimulating TGFBR2 expression and TGFβ signaling, while L-2-HG epigenetically inhibits GABPA expression, disrupting the GABPA-TGFβ loop to drive ccRCC aggressiveness. These results exemplify how oncometabolites erase tumor suppressive function for cancer development/progression. Restoring GABPA expression using DNA methylation inhibitors or other approaches, rather than targeting it, may be a novel strategy for ccRCC therapy.
Plasma circRNA microarray profiling identifies novel circRNA biomarkers for the diagnosis of ovarian cancer
Authors: Ge Lili , Sun Yu , Shi Yaqian , Liu Guangquan , Teng Fang , Geng Zhe , Chen Xiyi , Xu Hanzi , Xu Juan , Jia Xuemei
Published: May 2022

Background

Circular RNA (circRNA), a class of RNA with a covalent closed circular structure that widely existed in serum and plasma, has been considered an ideal liquid biopsy marker in many diseases. In this study, we employed microarray and qRT-PCR to evaluate the potential circulating circRNAs with diagnostic efficacy in ovarian cancer.

Methods

We used microarray to explore the circRNA expression profile in ovarian cancer patients’ plasma and quantitative real-time (qRT)-PCR approach to assessing the candidate circRNA’s expression. Then the receiver operating characteristic (ROC) curve was employed to analyze the diagnostic values of candidate circRNAs. The diagnostic model circCOMBO was a combination of hsa_circ_0003972 and hsa_circ_0007288 built by binary logistic regression. Then bioinformatic tools were used to predict their potential mechanisms.

Results

Hsa_circ_0003972 and hsa_circ_0007288 were downregulated in ovarian cancer patients’ plasma, tissues, and cell lines, comparing with the controls. Hsa_circ_0003972 and hsa_circ_0007288 exhibited diagnostic values with the Area Under Curve (AUC) of 0.724 and 0.790, respectively. circCOMBO showed a better diagnostic utility (AUC: 0.781), while the combination of circCOMBO and carbohydrate antigen 125 (CA125) showed the highest diagnostic value (AUC: 0.923). Furthermore, the higher expression level of hsa_circ_0007288 in both plasma and ovarian cancer tissues was associated with lower lymph node metastasis potential in ovarian cancer.

Conclusions

Our results revealed that hsa_circ_0003972 and hsa_circ_0007288 may serve as novel circulating biomarkers for ovarian cancer diagnosis.
A de novo variant in CASK gene causing intellectual disability and brain hypoplasia: a case report and literature review
Authors: Zhang Ying , Nie Yanyan , Mu Yu , Zheng Jie , Xu Xiaowei , Zhang Fang , Shu Jianbo , Liu Yang
Published: May 2022

Background

The pathogenic variation of CASK gene can cause CASK related mental disorders. The main clinical manifestations are microcephaly with pontine and cerebellar hypoplasia, X-linked mental disorders with or without nystagmus and FG syndrome. The main pathogenic mechanism is the loss of function of related protein caused by variant. We reported a Chinese male newborn with a de novo variant in CASK gene.

Case presentation

We present an 18-day-old baby with growth retardation and brain hypoplasia. Whole-exome sequencing was performed, which detected a hemizygous missense variant c.764G > A of CASK gene. The variant changed the 255th amino acid from Arg to His. Software based bioinformatics analyses were conducted to infer its functional effect.

Conclusions

In this paper, a de novo variant of CASK gene was reported. Moreover, a detailed description of all the cases described in the literature is reported. CASK variants cause a variety of clinical phenotypes. Its diagnosis is difficult due to the lack of typical clinical symptoms. Genetic testing should be performed as early as possible if this disease is suspected. This case provides an important reference for the diagnosis and treatment of future cases.
Association between gaseous air pollutants and idiopathic nephrotic syndrome in children: a 12-year population-based cohort study
Authors: Wang Chieh , Tsai Jeng-Dau , Wan Lei , Lin Cheng-Li , Wei Chang-Ching
Published: May 2022

Background

To date, there is insufficient knowledge about the association of air pollution and childhood nephrotic syndrome in the real world. This study aimed to evaluate the effects of the three common gaseous air pollutants, including sulfur dioxide, total hydrocarbon, and methane, on the risk of idiopathic nephrotic syndrome (INS) in children.

Methods

We collected data from the Taiwan National Health Insurance Research Database and Taiwan Air Quality-Monitoring Database. Children younger than 18 years old, identified from January 1, 2000, were followed up until the first diagnosis of INS was established or until December 31, 2012. We measured the incidence rates and hazard ratios for INS stratified based on the quartiles (Q1–Q4) of air pollutant concentration. Multivariate Cox proportional hazards models were also applied by adjusting age, sex, monthly income, and urbanization.

Results

Compared with participants exposed to Q1 concentrations, the adjusted hazard ratios (aHRs) for INS increased progressively along the four quartiles of sulfur dioxide, total hydrocarbon, and methane, from 1 (Q1) to 1.78 (Q4), 1 (Q1) to 3.49 (Q4), 1 (Q1) to 7.83 (Q4), respectively.

Conclusions

Our study revealed that children with exposure to higher concentrations of sulfur dioxide, total hydrocarbon, and methane was associated with an increased risk of INS.
Hemoperfusion: technical aspects and state of the art
Authors: Ronco Claudio , Bellomo Rinaldo
Published: May 2022

Background

Blood purification through the removal of plasma solutes by adsorption to beads of charcoal or resins contained in a cartridge (hemoperfusion) has a long and imperfect history. Developments in production and coating technology, however, have recently increased the biocompatibility of sorbents and have spurred renewed interest in hemoperfusion.

Methods

We performed a narrative assessment of the literature with focus on the technology, characteristics, and principles of hemoperfusion. We assessed publications in ex vivo, animal, and human studies. We synthesized such literature in a technical and state-of-the-art summary.

Results

Early hemoperfusion studies were hampered by bioincompatibility. Recent technology, however, has improved its safety. Hemoperfusion has been used with positive effects in chronic dialysis and chronic liver disease. It has also demonstrated extraction of a variety of toxins and drugs during episodes of overdose. Trials with endotoxin binding polymyxin B have shown mixed results in septic shock and are under active investigation. The role of non-selective hemoperfusion in sepsis or inflammation remains. Although new technologies have made sorbents more biocompatible, the research agenda in the field remains vast.

Conclusion

New sorbents markedly differ from those used in the past because of greater biocompatibility and safety. Initial studies of novel sorbent-based hemoperfusion show some promise in specific chronic conditions and some acute states. Systematic studies of novel sorbent-based hemoperfusion are now both necessary and justified.
Success and failure factors of patient recruitment for industry-sponsored clinical trials and the role of the electronic health records—a qualitative interview study in the Nordic countries
Authors: Laaksonen Niina , Bengtström Mia , Axelin Anna , Blomster Juuso , Scheinin Mika , Huupponen Risto
Published: May 2022

Background

Patient recruitment for clinical trials is challenging—only approximately one third of all trials recruit their participants as planned. The pharmaceutical industry’s views on recruitment success have not been comprehensively investigated, although the industry globally conducts almost one third of all clinical drug trials. This study explored patient recruitment success and failure factors and the role of electronic health records (EHR) in the recruitment of trial participants in the Nordic countries.

Methods

A descriptive qualitative interview study was conducted with 21 representatives of the pharmaceutical industry or contract research organizations operating in Finland, Sweden, Denmark, and Norway. The interviews covered 34 clinical pre-market drug trials. Qualitative data were analyzed using inductive content analysis.

Results

Four main categories were derived to represent both success and failure factors, whereas a fifth category represented only failure factors: (1) sponsor-related (protocol and trial preparation and feasibility evaluations), (2) site/investigator-related (access to patients, motivation, commitment and resources), (3) patient-related recruitment factors (medical need, patients’ role in their care and attitudes towards trials), (4) Sponsor—sites—patients collaboration factors, and (5) start-up related factors. EHR was the most important source of recruitment, utilized in 29 out of 34 trials discussed. Revision of the legislation regulating the secondary use of EHR was highlighted as the most effective measure to facilitate the use of EHR in recruitment of trial participants.

Conclusions

The industry representatives recognized quite well their own role in contributing to the success or failure of the recruitment: to facilitate recruitment of trial participants, many obstacles can be avoided with better trial preparation and proper feasibility evaluations. As access to patients represents one of the key success or failure factors of recruitment, and as the EHR is regarded the main source of searching for and finding patients, the development of EHR utilization appears to represent a powerful tool to improve patient recruitment.
Impact of El-Poems study: the e-learning for postural education in music students: a randomized controlled trial protocol
Authors: Akbari-Chehrehbargh Zahra , Tavafian Sedigheh Sadat
Published: May 2022

Background

Musculoskeletal pain (MP) has today intensified in a large proportion of music students in Iran. Poor posture while playing an instrument is thus assumed as a very significant risk factor affecting such a condition in this population. The present study aims to evaluate the impact of electronic learning (e-learning) for postural education to music students on posture behavior and MP (abbreviated as an El-Poems study).

Methods

This study is a matched-pair, two-arm, parallel randomized controlled trial (RCT). The participants, as the 7th-to-12th-grade music students, will be accordingly assigned to intervention (n = 204) and control (n = 204) groups, based on the inclusion and exclusion criteria. The postural education will be also presented through the web-based Student Education Network (with the acronym, SHAD) at the Tehran Conservatory of Music, Tehran, Iran. The intervention program consists of four sessions, using the Integrated Change (I-Change) model. It will be also implemented by a trained physical education instructor and a health educator. The content of the program includes raising awareness, building motivation, and developing skills. Besides, its components are comprised of specific proper postures viz. standing, sitting, lifting, carrying, and hand position while playing a musical instrument. The primary outcome is the MP that will be assessed by the Nordic Body Map (NBM) questionnaire and a numerical rating scale (NRS), and the secondary outcome is the posture behavior that will be evaluated objectively, using the Rapid Entire Body Assessment (REBA) tool. The data will be also collected at baseline and after a six-month follow-up.

Conclusion

This RCT is an innovative study as a pioneer to represent the first attempt for web-based postural education as well as an attractive intervention to prevent MP in Iranian music students.

Trial registration

Current Controlled Trials IRCT20180528039885N2. Prospectively registered on 11 September 2021
Efficacy and safety of Tibetan medicine Qingpeng ointment for acute gouty arthritis: protocol for a multi-center, randomized, double-blind, placebo-controlled trial
Authors: Shang Ya-xi , Dong Xia , Xie Zhi-min , Li Xiao-peng , Wang Xin-chang , Huang Ji-yong , Wei Shu-feng , Liu Yuan , Liu Jian-ping
Published: May 2022

Background

Acute gouty arthritis (AGA) is an inflammatory arthritis clinically characterized by severe pain, swelling, and restricted movement of joints, which may cause physical disability and decrease quality of life. The use of recommended first-line treatment agents for AGA may be limited by adverse events. There has been a traditional use of alternative therapies for AGA. Tibetan medicine Qingpeng ointment is one of the on-market herbal products used for symptom relief of AGA. Previous clinical studies indicated that Qingpeng ointment can relieve pain, swelling, redness, and dysfunction of joints in patients with AGA. However, there is no rigorous randomized trial to demonstrate its benefit for AGA. In order to evaluate the efficacy and safety of Qingpeng ointment for AGA, we designed a randomized controlled trial.

Methods

This study is designed as a multi-center, randomized, double-blind, placebo-controlled trial. Two hundred and six adults with acute flare of gout, and visual analogue scale (VAS) score of joint pain ≥ 3 points will be recruited. Participants will be randomly assigned to herbal treatment or placebo group at a ratio of 1:1. Qingpeng ointment, or equal placebo ointment, will be applied topically at involved joints twice a day for consecutive 7 days. Patients in both groups would be allowed giving diclofenac sodium sustained-release tablets as rescue therapy when VAS score of joint pain ≥ 7 points during the treatment. The primary outcomes will be joint pain measured by VAS score, and joint swelling measured using width and thickness of affected joints and VAS score. Other outcome measures will be joint mobility, joint redness, C-reactive protein, serum uric acid, and the use of rescue medicine as well as adverse effect.

Discussion

To the best of our knowledge, this study is the first multi-center, randomized, double-blind, and placebo-controlled clinical trial to assess the efficacy of Tibetan medicine Qingpeng ointment for AGA. The findings of this study would provide evidence for its use to relieve symptoms of AGA.

Trial registration

ISRCTN ISRCTN34355813. Registered on 25 January 2021
Internet of things-based home noninvasive ventilation in COPD patients with hypercapnic chronic respiratory failure: study protocol for a randomized controlled trial
Authors: Jiang Weipeng , Song Yuanlin
Published: May 2022

Background

Home noninvasive positive pressure ventilation (NIPPV) has become evidence-based care for stable hypercapnic chronic obstructive pulmonary disease (COPD) patients. There are still other challenges including appropriate follow-up, telemonitor, and management to ensure treatment effectiveness, compliance, and security and to improve quality of life. The Internet of things (IOT) is the name given to the network of devices and other “things” with built-in sensors, software, electronics, and network connectivity, communicating these objects over wireless networks and sending data to a cloud platform. The study aims to evaluate the effectiveness and safety of the IOT-based management of NIPPV for the COPD patients with hypercapnic chronic respiratory failure.

Methods

This multicenter, prospective, randomized controlled trial was conducted with a total of 200 COPD patients with chronic hypercapnic respiratory failure. Using a computer-generated randomization process, patients were randomized (in a 1:1 ratio) into the usual NIPPV (control group) or to receive additional IOT-based management (intervention group) for 12 months. The primary outcome was the Severe Respiratory Insufficiency (SRI) questionnaire. Secondary outcomes included compliance with the ventilator, gas exchange, lung function, health-related quality of life, hospitalization frequency, time to death within 1-year, all-cause mortality, safety analysis, and cost-effectiveness analysis.

Discussion

This study will be the first and largest randomized trial in China to evaluate the effectiveness and safety of the IOT-based management of NIPPV for COPD patients with chronic hypercapnic respiratory failure. The results will help to understand the current situation of IOT-based home ventilation and may provide new evidence for home NIPPV treatment and management in the future.

Trial registration

Chinese Clinical Trials Registry ChiCTR1800019536. Registered on 17 November 2018.
Comparison of FECPAKG2, a modified Mini-FLOTAC technique and combined sedimentation and flotation for the coproscopic examination of helminth eggs in horses
Authors: Boelow Heike , Krücken Jürgen , Thomas Eurion , Mirams Greg , von Samson-Himmelstjerna Georg
Published: May 2022

Background

Due to high prevalence of anthelmintic resistance in equine helminths, selective treatment is increasingly promoted and in some countries a positive infection diagnosis is mandatory before treatment. Selective treatment is typically recommended when the number of worm eggs per gram faeces (epg) exceeds a particular threshold. In the present study we compared the semi-quantitative sedimentation/flotation method with the quantitative methods Mini-FLOTAC and FECPAKG2 in terms of precision, sensitivity, inter-rater reliability and correlation of worm egg counts to improve the choice of optimal diagnostic tools.

Methods

Using sedimentation/flotation (counting raw egg numbers up to 200), we investigated 1067 horse faecal samples using a modified Mini-FLOTAC approach (multiplication factor of 5 to calculate epgs from raw egg counts) and FECPAKG2 (multiplication factor of 45).

Results

Five independent analyses of the same faecal sample with all three methods revealed that variance was highest for the sedimentation/flotation method while there were no significant differences between methods regarding the coefficient of variance. Sedimentation/flotation detected the highest number of samples positive for strongyle and Parascaris spp. eggs, followed by Mini-FLOTAC and FECPAKG2. Regarding Anoplocephalidae, no significant difference in frequency of positive samples was observed between Mini-FLOTAC and sedimentation/flotation. Cohen’s κ values comparing individual methods with the combined result of all three methods revealed almost perfect agreement (κ ≥ 0.94) for sedimentation/flotation and strong agreement for Mini-FLOTAC (κ ≥ 0.83) for strongyles and Parascaris spp. For FECPAKG2, moderate and weak agreements were found for the detection of strongyle (κ = 0.62) and Parascaris (κ = 0.51) eggs, respectively. Despite higher sensitivity, the Mini-FLOTAC mean epg was significantly lower than that with FECPAKG2 due to samples with > 200 raw egg counts by sedimentation/flotation, while in samples with lower egg shedding epgs were higher with Mini-FLOTAC than with FECPAKG2.

Conclusions

For the simple detection of parasite eggs, for example, to treat foals infected with Parascaris spp., sedimentation/flotation is sufficient and more sensitive than the other two quantitative investigared in this study. Mini-FLOTAC is predicted to deliver more precise results in faecal egg count reduction tests due to higher raw egg counts. Finally, to identify animals with a strongyle epg above a certain threshold for treatment, FECPAKG2 delivered results comparable to Mini-FLOTAC.

Grpahical Abstract
Development of a multisystem point of care ultrasound skills assessment checklist
Authors: Soni Nilam J. , Nathanson Robert , Andreae Mark , Khosla Rahul , Vadamalai Karthik , Kode Karthik , Boyd Jeremy S. , LoPresti Charles M. , Resop Dana , Basrai Zahir , Williams Jason , Bales Brian , Sauthoff Harald , Wetherbee Erin , Haro Elizabeth K. , Smith Natalie , Mader Michael J. , Pugh Jacqueline , Finley Erin P. , Schott Christopher K.
Published: May 2022

Background

Many institutions are training clinicians in point-of-care ultrasound (POCUS), but few POCUS skills checklists have been developed and validated. We developed a consensus-based multispecialty POCUS skills checklist with anchoring references for basic cardiac, lung, abdominal, and vascular ultrasound, and peripheral intravenous line (PIV) insertion.

Methods

A POCUS expert panel of 14 physicians specializing in emergency, critical care, and internal/hospital medicine participated in a modified-Delphi approach to develop a basic POCUS skills checklist by group consensus. Three rounds of voting were conducted, and consensus was defined by ≥ 80% agreement. Items achieving < 80% consensus were discussed and considered for up to two additional rounds of voting.

Results

Thirteen POCUS experts (93%) completed all three rounds of voting. Cardiac, lung, abdominal, and vascular ultrasound checklists included probe location and control, basic machine setup, image quality and optimization, and identification of anatomical structures. PIV insertion included additional items for needle tip tracking. During the first round of voting, 136 (82%) items achieved consensus, and after revision and revoting, an additional 21 items achieved consensus. A total of 153 (92%) items were included in the final checklist.

Conclusions

We have developed a consensus-based, multispecialty POCUS checklist to evaluate skills in image acquisition and anatomy identification for basic cardiac, lung, abdominal, and vascular ultrasound, and PIV insertion.
Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration
Authors: Zeni Letizia , Norden Anthony G. W. , Prandi Elena , Canepa Carolina , Burling Keith , Simpson Katherine , Felappi Barbara , Plebani Alessandro , Cancarini Giovanni , Ferraro Pietro Manuel , Fraser Donald , Unwin Robert J.
Published: May 2022

Background

The pathogenesis of diabetic kidney disease (DKD) is complex and involves both glomerular and tubular dysfunction. A global assessment of kidney function is necessary to stage DKD, a progressive kidney disease that is likely to begin in childhood. The present study evaluated whether kidney injury biomarkers identified as early DKD biomarkers in adults have any prognostic value in the very early stages of childhood diabetes.

Methods

We measured urine free Retinol-binding protein 4 (UfRBP4), albumin (UAlb), Kidney injury molecule-1 (KIM-1) and the microRNAs miR-155, miR-126 and miR-29b in two cohorts of paediatric T1DM patients without evidence of DKD, but with diabetes of short-duration, ≤ 2.5 years (SD, n = 25) or of long-duration, ≥ 10 years (LD, n = 29); non-diabetic siblings (H, n = 26) were recruited as controls. A p value < 0.05 was considered significant for all results.

Results

UfRBP4 and UAlb were not significantly different across the three groups. No differences were found in KIM-1 excretion between any of the three groups. UfRBP4 was correlated with UAlb in all three groups (r 0.49; p < 0.001), whereas KIM-1 showed no correlation with albumin excretion. Among microRNAs, miR-29b was higher in all diabetic children compared with the H control group (p = 0.03), whereas miR-155 and miR-126 were not significantly different. No differences were found between the SD and LD groups for all three microRNAs. No associations were identified between these biomarkers with sex, age, BMI, eGFR, T1DM duration or glycaemic control.

Conclusions

UfRBP4, KIM-1, miR-155, and miR-126 were unaffected by the presence and duration of diabetes, whereas miR-29b showed a modest elevation in diabetics, regardless of duration. These data support the specificity of a panel of urine biomarkers as DKD biomarkers, rather than any relationship to diabetes per se or its duration, and not as early DKD biomarkers in a paediatric setting.
β-Amyloid in blood neuronal-derived extracellular vesicles is elevated in cognitively normal adults at risk of Alzheimer’s disease and predicts cerebral amyloidosis
Authors: Li Tao-Ran , Yao Yun-Xia , Jiang Xue-Yan , Dong Qiu-Yue , Yu Xian-Feng , Wang Ting , Cai Yan-Ning , Han Ying
Published: May 2022

Background

Blood biomarkers that can be used for preclinical Alzheimer’s disease (AD) diagnosis would enable trial enrollment at a time when the disease is potentially reversible. Here, we investigated plasma neuronal-derived extracellular vesicle (nEV) cargo in patients along the Alzheimer’s continuum, focusing on cognitively normal controls (NCs) with high brain β-amyloid (Aβ) loads (Aβ+).

Methods

The study was based on the Sino Longitudinal Study on Cognitive Decline project. We enrolled 246 participants, including 156 NCs, 45 amnestic mild cognitive impairment (aMCI) patients, and 45 AD dementia (ADD) patients. Brain Aβ loads were determined using positron emission tomography. NCs were classified into 84 Aβ− NCs and 72 Aβ+ NCs. Baseline plasma nEVs were isolated by immunoprecipitation with an anti-CD171 antibody. After verification, their cargos, including Aβ, tau phosphorylated at threonine 181, and neurofilament light, were quantified using a single-molecule array. Concentrations of these cargos were compared among the groups, and their receiver operating characteristic (ROC) curves were constructed. A subset of participants underwent follow-up cognitive assessment and magnetic resonance imaging. The relationships of nEV cargo levels with amyloid deposition, longitudinal changes in cognition, and brain regional volume were explored using correlation analysis. Additionally, 458 subjects in the project had previously undergone plasma Aβ quantification.

Results

Only nEV Aβ was included in the subsequent analysis. We focused on Aβ42 in the current study. After normalization of nEVs, the levels of Aβ42 were found to increase gradually across the cognitive continuum, with the lowest in the Aβ− NC group, an increase in the Aβ+ NC group, a further increase in the aMCI group, and the highest in the ADD group, contributing to their diagnoses (Aβ− NCs vs. Aβ+ NCs, area under the ROC curve values of 0.663; vs. aMCI, 0.857; vs. ADD, 0.957). Furthermore, nEV Aβ42 was significantly correlated with amyloid deposition, as well as longitudinal changes in cognition and entorhinal volume. There were no differences in plasma Aβ levels among NCs, aMCI, and ADD individuals.

Conclusions

Our findings suggest the potential use of plasma nEV Aβ42 levels in diagnosing AD-induced cognitive impairment and Aβ+ NCs. This biomarker reflects cortical amyloid deposition and predicts cognitive decline and entorhinal atrophy.
Assessing the impact of gestational age of donors on the efficacy of amniotic epithelial cell-derived extracellular vesicles in experimental bronchopulmonary dysplasia
Authors: Zhu Dandan , Krause Mirja , Yawno Tamara , Kusuma Gina D. , Schwab Renate , Barabadi Mehri , Maleken Amina S. , Chan Siow T. , Hunt Rod , Greening David , Wallace Euan M. , Lim Rebecca
Published: May 2022

Background and rationale

Extracellular vesicles (EVs) are a potential cell-free regenerative medicine. Human amniotic epithelial cells (hAECs) are a viable source of cell therapy for diseases like bronchopulmonary dysplasia (BPD). However, little is known about the impact of gestational age of the donor on the quality of hAEC-derived EVs.

Aims

To determine the impact of gestational age on hAEC-derived EVs in experimental BPD.

Results

Term hAEC-derived EVs displayed a significantly higher density of surface epitopes (CD142 and CD133) and induced greater macrophage phagocytosis compared to preterm hAEC-EVs. However, T cell proliferation was more significantly suppressed by preterm hAEC-EVs. Using a model of experimental BPD, we observed that term but not preterm hAEC-EVs improved tissue-to-airspace ratio and septal crest density. While both term and preterm hAEC-EVs reduced the levels of inflammatory cytokines on postnatal day 7, the improvement in lung injury was associated with increased type II alveolar cells which was only observed in term hAEC-EV treatment group. Furthermore, only neonatal term hAEC-EVs reduced airway hyper-responsiveness, mitigated pulmonary hypertension and protected against right ventricular hypertrophy at 6 weeks of age.

Conclusion

Term hAEC-EVs, but not preterm hAEC-EVs, have therapeutic efficacy in a mouse model of BPD-like lung injury. Therefore, the impact of donor criteria should be considered when applying perinatal cells-derived EV therapy for clinical use.
Potential mechanisms and therapeutic targets of mesenchymal stem cell transplantation for ischemic stroke
Authors: Zhou Li , Zhu Huimin , Bai Xue , Huang Jiagui , Chen Yue , Wen Jun , Li Xuemei , Wu Bowen , Tan Yongjun , Tian Mingfen , Ren Jiangxia , Li Mengxia , Yang Qin
Published: May 2022

Ischemic stroke is one of the major causes of death and disability in the world. Currently, most patients cannot choose intravenous thrombolysis or intravascular mechanical thrombectomy because of narrow therapeutic windows and severe complications. Stem cell transplantation is an emerging treatment and has been studied in various central nervous system diseases. Animal and clinical studies showed that transplantation of mesenchymal stem cells (MSCs) could alleviate neurological deficits and bring hope for ischemic stroke treatment. This article reviewed biological characteristics, safety, feasibility and efficacy of MSCs therapy, potential therapeutic targets of MSCs, and production process of Good Manufacturing Practices-grade MSCs, to explore the potential therapeutic targets of MSCs in the process of production and use and provide new therapeutic directions for ischemic stroke.
A myxobacterial GH19 lysozyme with bacteriolytic activity on both Gram-positive and negative phytopathogens
Authors: Li Yueqiu , Zhou Xiaoli , Zhang Xianjiao , Xu Zhiqiang , Dong Honghong , Yu Guohui , Cheng Ping , Yao Qing , Zhu Honghui
Published: May 2022

Myxobacteria, as predatory bacteria, have good application potential in the biocontrol of pathogenic microorganisms. Extracellular enzymes are thought to play an important role in their predation and also provide resources for discovering new antibacterial molecules. We previously isolated a myxobacterium, Corallococcus silvisoli c25j21 GDMCC 1.1387, which is predatory to plant pathogenic bacteria. In this study, we identified an endolysin-like GH19 glycoside hydrolase, C25GH19B, from the genome of c25j21. After its heterologous expression and purification from E. coli, the enzymatic properties of C25GH19B were characterized. C25GH19B showed lysozyme activity with the optimal reaction conditions at 40 °C and pH 4.5–5.0. Moreover, C25GH19B showed bacteriolytic activity against both Gram-positive and Gram-negative plant pathogenic bacteria. Our research provides not only a candidate enzyme for the development of novel biocontrol agents but also an experimental basis for further study on the function and mechanisms of extracellular enzymes in myxobacterial predation.
Virtual full-duplex buffer-aided relay selection schemes for secure cooperative wireless networks
Authors: Zhou Jiayu , Qiao Deli , Qian Haifeng
Published: May 2022

This paper considers secure communication in buffer-aided cooperative wireless networks in the presence of one eavesdropper, which can intercept the data transmission from both the source and relay nodes. It is assumed that the relays employ the randomize-and-forward (RF) strategy such that the eavesdropper can only decode the signals received in the two hops independently. Two cooperative secure transmission schemes, i.e., hybrid imitating full-duplex max-max-ratio relay selection (HyIFD) scheme and threshold-based link selection (TBLS) scheme are proposed for adaptive- and fixed-rate transmissions aiming at improving the secrecy throughput and secrecy outage probability, respectively. For adaptive-rate transmissions (ART), the proposed scheme switches among three sub-strategies according to different conditions such as the number of relays and transmit power. Different relays are chosen for reception and transmission according to the ratio of the legitimate channels to the eavesdropper channels to imitate the full-duplex transmission mode. For fixed-rate transmissions (FRT), a hybrid HD/FD transmission mode is designed to increase the transmission probabilities of two hops under the transmission quality constraint. Two parameters are introduced and optimized to minimize the secrecy outage probability. A sub-optimal TBLS (SO-TBLS) scheme is also given. Theoretical analysis of the secrecy throughput and the secrecy outage probability are provided and the closed-form expressions are derived, and verified by numerical results. It is shown that the proposed schemes outperform benchmark schemes in terms of secrecy throughput and secrecy outage probability.
Observer-based event-triggered finite-time consensus for general linear leader-follower multi-agent systems
Authors: Luo Yiping , Pang Jialong
Published: May 2022

In this study, the event-triggered finite-time consensus problem of a class of general linear leader-follower multi-agent systems with unmeasurable states is investigated. First, an observer-based distributed event-triggered strategy is proposed in view of introducing an external dynamic threshold that is independent of the state variables. Second, the Lyapunov method and proposed event-triggered strategy are implemented as the control scheme to ensure that the tracking error can converge to the origin within a finite time under given conditions. Analytical findings indicate that the Zeno behavior can be avoided by selecting the appropriate parameters. Finally, a numerical simulation is implemented, and the results verify the effectiveness of the proposed method.
Precocious puberty related to Leydig cell testicular tumor: the diagnostic imaging keys
Authors: Grand Téodor , Hermann Anne-Laure , Gérard Maxime , Arama Emmanuel , Ouerd Linda , Garrouche Nada , Rocher Laurence
Published: May 2022

Background

We report the challenging case of a 6-year-old boy with precocious puberty related to histologically proven Leydig cell tumor.

Case presentation

Multiparametric ultrasound and magnetic resonance imaging (MRI) was performed. Interesting findings were scarcely or never reported in children and differed from adults Leydig cell tumors s such as the hyperechogenic halo surrounding the lesion and the dominant central vascularization using ultrasensitive Doppler. MRI revealed an enlarged testicle with strong enhancement of a tumor, a tumor apparent diffusion coefficient (ADC) of 600 × 10−3 mm2/s and a lower ADC value of the non-tumor parenchyma compared to the contralateral testis (ADC = 800 × 10−3 mm2/s vs 1100 × 10−3 mm2/s), attributed to the spermatogenesis induced by hormonal impregnation.

Conclusion

We illustrate multiparametric US and MRI findings of a pediatric Leydig cell tumor, including the imaging changes attributed to local hormone secretion, which may be helpful in similar cases.