bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric esophagogastroduodenoscopy in china: indications, diagnostic yield, and factors associated with findings
Authors: Wang Shengnan , Qiu Xiaoxia , Chen Jingfang , Mei Hong , Yan Haiyan , You Jieyu , Huang Ying
Published: September 2022

Background

Large-scale data on esophagogastroduodenoscopy (EGD) in China are scarce. This study aimed to assess the indications and diagnostic yield of EGD in children and the relationship between factors (such as age, sex, and indications) and diagnostic yield.

Methods

We performed a prospective cross-sectional observational study involving patients aged < 18 years who underwent diagnostic EGD. The study was conducted in five children’s hospitals, each in a different city. Demographic features, indications for endoscopy, and endoscopic and histopathological findings were collected. Univariable and multivariable ordinal logistic regression analyses of the relationship between the factors and diagnostic yield were performed.

Results

The study included 2268 patients (male/female ratio, 1.3:1) with a median age of 8.68 years. Among the 2268 children, the most frequent indications were abdominal pain in 1954 (86.2%), recurrent vomiting in 706 (31.1%), weight loss in 343 (15.1%), and others. The endoscopic yield was 62.5% and was the highest in patients with dysphagia (90.9%). The histologic yield was 30.4% and was the highest in patients with unexplained anemia (45.5%). On multivariable regression analysis, the endoscopic yield was associated with dysphagia, gastrointestinal (GI) bleeding, and recurrent vomiting, and the histologic yield was associated with age. Different groups of patients with abdominal pain had variable probabilities of abnormal endoscopic findings.

Conclusions

The most frequent indication of pediatric EGD is abdominal pain, with variable probabilities of abnormal endoscopic findings in different groups. Endoscopic yield and histologic yield are associated with certain alarming features.

Trial registration

The trial registration number (ClinicalTrials. gov): NCT03603093 (The study was registered on 27/07/2018).
A School Eye Health Rapid Assessment (SEHRA) planning tool: Module to survey the magnitude and nature of local needs
Authors: Morjaria Priya , Massie Jessica , Bastawrous Andrew ,   SEHRA Author Group, Awan Haroon , Borah Rishi Raj , Buglass Anne , Congdon Nathan , Davis Amanda , Dodson Sarity , Faal Hannah , Gilbert Clare , Ho May , Keys Drew , Limburg Hans , MacTaggart Islay , McCormick Ian , Naidoo Kovin , Nsubunga Naomi , Philippin Heiko , Rabiu Mansur , Ramke Jacqui , Resnikoff Serge , Sapkota Yuddha , Shamana B. R. , Smith Elizabeth , Stern Jude , Varga Beatrice , Yasmin Sumrana
Published: September 2022

Background

Eye conditions in children can have negative consequences on visual functioning and quality of life. There is a lack of data on the magnitude of children with eye conditions who need services for effective planning of school eye health programmes. To address this, the School Eye Health Rapid Assessment (SEHRA) tool is being developed to collect data to support school eye health programme planning.

Methods

The module, ‘the magnitude and nature of local needs in school children’ is the first of six modules in the SEHRA tool. The module outlines a school-based cluster survey designed to determine the magnitude of eye health needs in children. This paper outlines the survey sampling strategy, and sample size calculations.

Results

The requirements for the SEHRA survey indicate that in regions where a larger sample size is required, or where fewer schools are recruited to the survey, confidence in the accuracy of the data will be lower.

Conclusions

The SEHRA survey module ‘the magnitude and nature of local needs in school children’ can be applied in any context. In certain circumstances, the confidence in the survey data will be reduced.
A scoring model for diagnosis of tuberculous pleural effusion
Authors: Wu Senquan , Li Shaomei , Fang Nianxin , Mo Weiliang , Wang Huadong , Zhang Ping
Published: September 2022

Background

Due to the low efficiency of a single clinical feature or laboratory variable in the diagnosis of tuberculous pleural effusion (TBPE), the diagnosis of TBPE is still challenging. This study aimed to build a scoring diagnostic model based on laboratory variables and clinical features to differentiate TBPE from non-tuberculous pleural effusion (non-TBPE).

Methods

A retrospective study of 125 patients (63 with TBPE; 62 with non-TBPE) was undertaken. Univariate analysis was used to select the laboratory and clinical variables relevant to the model composition. The statistically different variables were selected to undergo binary logistic regression. Variables B coefficients were used to define a numerical score to calculate a scoring model. A receiver operating characteristic (ROC) curve was used to calculate the best cut-off value and evaluate the performance of the model. Finally, we add a validation cohort to verify the model.

Results

Six variables were selected in the scoring model: Age ≤ 46 years old (4.96 points), Male (2.44 points), No cancer (3.19 points), Positive T-cell Spot (T-SPOT) results (4.69 points), Adenosine Deaminase (ADA) ≥ 24.5U/L (2.48 point), C-reactive Protein (CRP) ≥ 52.8 mg/L (1.84 points). With a cut-off value of a total score of 11.038 points, the scoring model’s sensitivity, specificity, and accuracy were 93.7%, 96.8%, and 99.2%, respectively. And the validation cohort confirms the model with the sensitivity, specificity, and accuracy of 92.9%, 93.3%, and 93.1%, respectively.

Conclusion

The scoring model can be used in differentiating TBPE from non-TBPE.
Healthcare service utilization of hill tribe children in underserved communities in Thailand: barriers to access
Authors: Moonpanane Katemanee , Pitchalard Khanittha , Thepsaw Jintana , Singkhorn Onnalin , Potjanamart Chomnard
Published: September 2022

Background

Hill tribe children, an ethnic minority group in Thailand, experience wide-ranging social and health inequalities. Previous reports indicate that hill tribe children, especially age under 5 years, face social health disadvantages but little is known about the underlying causes. Exploring healthcare utilization among hill tribe children is therefore essential and it may well provide some insight.

Methods

A qualitative study was conducted using purposive sampling techniques to recruit participants based on our criteria. In-depth interviews and focus-group discussions were employed to explore the experiences of parents (n = 20), community leaders (n = 20), and healthcare providers (n = 20) when caring for children aged under 5 years. Interview transcripts were coded, and thematic analysis was then performed.

Results

The participants shared their experiences with accessing healthcare services in underserved areas. Barriers to access was the central theme identified. Sub-themes included: (1) distance matters, (2) education and socioeconomic deprivation, (3) lack of cultural sensitivity, (4) communication problems, (5) tradition, beliefs, and differences in cultural practice, (6) lack of child health professionals, and (7) bureaucratic hurdles.

Conclusions

Healthcare services and environments must be transformed to provide healthcare services, education, and information appropriate to the cultures and beliefs prevalent in the hill tribe population.
Effect of sorafenib maintenance on Epstein-Barr virus and cytomegalovirus infections in patients with FLT3-ITD AML undergoing allogeneic hematopoietic stem cell transplantation: a secondary analysis of a randomized clinical trial
Authors: Xu Xin , Fan Zhiping , Wang Yu , Huang Fen , Xu Yajing , Sun Jing , Xu Na , Deng Lan , Li Xudong , Liang Xinquan , Luo Xiaodan , Shi Pengcheng , Liu Hui , Chen Yan , Tu Sanfang , Huang Xiaojun , Liu Qifa , Xuan Li
Published: September 2022

Background

Use of kinase inhibitors such as dasatinib and imatinib might increase the risk of opportunistic infections, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. However, the effect of sorafenib on EBV and CMV infections remains unclear. The aim of this study was to investigate the effect of sorafenib maintenance post-transplantation on the incidence and mortality of EBV and CMV infections in patients with FLT3-ITD acute myeloid leukemia.

Methods

This was a follow-up of our randomized controlled trial undertaken at seven hospitals in China. The primary endpoint was EBV and CMV infections within 3 years post-transplantation. Secondary endpoints included the cumulative incidences of relapse, non-relapse mortality (NRM), overall survival (OS), leukemia-free survival (LFS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) at 3 years.

Results

Two hundred two patients were assigned to sorafenib maintenance (n=100) or non-maintenance (control, n=102). Median extended follow-up post-transplantation was 36.8 (range, 2.5–67.1) months. The 3-year cumulative incidences of EBV-DNAemia and EBV-associated diseases were 24.0% (95% CI: 16.1–32.8%) and 5.0% (1.8–10.6%) in the sorafenib group, and 24.5% (16.6–33.2%) and 5.9% (2.4–11.6%) in the control group (P=0.937; P=0.771). The 3-year cumulative incidences of CMV-DNAemia and CMV-associated diseases were 56.0% (45.6–65.1%) and 8.0% (3.7–14.4%) in the sorafenib group, and 52.9% (42.7–62.1%) and 8.8% (4.3–15.3%) in the control group (P=0.997; P=0.826). The 3-year cumulative mortality of EBV- and CMV-associated diseases was 0.0% (0.0–0.0%) and 2.0% (0.4–6.4%) in the sorafenib group, and 1.0% (0.1–4.8%) and 2.0% (0.4–6.3%) in the control group (P=0.322, P=0.980). The 3-year cumulative incidences of relapse, NRM, OS, LFS, and GRFS were 13.0%, 11.1%, 79.0%, 75.9%, and 65.8% in the sorafenib group and 34.8%, 12.7%, 61.4%, 52.5%, and 46.6% in the control group, respectively (P<0.001, P=0.656, P=0.005, P<0.001, P=0.003). The reconstitution of T lymphocyte subsets, B lymphocytes, and natural killer cells was similar between the two groups (all P>0.05).

Conclusions

Sorafenib maintenance post-transplantation does not increase the incidence and mortality of EBV and CMV infections, demonstrating a favorable safety profile.

Trial registration

ClinicalTrials.gov Identifier: NCT02474290. Registered on June 14, 2015
Effectiveness and profitability of preventive veterinary interventions in controlling infectious diseases of ruminant livestock in sub-Saharan Africa: a scoping review
Authors: Nuvey Francis Sena , Arkoazi Jalil , Hattendorf Jan , Mensah Gloria Ivy , Addo Kennedy Kwasi , Fink Günther , Zinsstag Jakob , Bonfoh Bassirou
Published: September 2022

Agriculture in general, and livestock production in particular, serve as a livelihood source for many people in sub-Saharan Africa (SSA). In many settings, lack of control of infectious diseases hampers livestock productivity, undermining the livelihood of rural populations. This scoping review sought to identify veterinary interventions previously evaluated as well as their relative effectiveness in controlling infectious livestock diseases. To be included, papers had to be written in English, German or French, and had to describe the effectiveness and/or profitability of preventive veterinary intervention(s) against anthrax, blackleg, bovine tuberculosis, brucellosis, contagious bovine pleuropneumonia, contagious caprine pleuropneumonia, foot-and-mouth disease, goat pox, lumpy skin disease, pasteurellosis, peste des petits ruminants, and/or sheep pox in any SSA country. Of the 2748 publications initially screened, 84 met our inclusion criteria and were analyzed. Most of the studies (n = 73, 87%) evaluated the effectiveness and/or profitability of vaccination, applied exclusively, applied jointly with, or compared to strategies like deworming, antimicrobial treatment, surveillance, feed supplementation, culling and dipping in reducing morbidity and/or mortality to livestock diseases. The effectiveness and/or profitability of antimicrobial treatment (n = 5), test and slaughter (n = 5), and use of lay animal health workers (n = 1) applied exclusively, were evaluated in the other studies. Vaccination was largely found to be both effective and with positive return on investment. Ineffective vaccination was mainly due to loss of vaccine potency under unfavorable field conditions like adverse weather events, cold chain failure, and mismatch of circulating pathogen strain and the vaccines in use.

In summary, vaccination is the most effective and profitable means of controlling infectious livestock diseases in SSA. However, to achieve effective control of these diseases, its implementation must integrate pathogen surveillance, and optimal vaccine delivery tools, to overcome the reported field challenges.
A long-term cost-effectiveness analysis of cardiac resynchronisation therapy with or without defibrillator based on health claims data
Authors: Hadwiger Moritz , Schumann Laura , Eisemann Nora , Dagres Nikolaos , Hindricks Gerhard , Haug Janina , Wolf Michael , Marschall Ursula , Katalinic Alexander , Frielitz Fabian-Simon
Published: September 2022

Background

In Germany, CRT devices with defibrillator capability (CRT-D) have become the predominant treatment strategy for patients with heart failure and cardiac dyssynchrony. However, according to current guidelines, most patients would also be eligible for the less expensive CRT pacemaker (CRT-P). We conducted a cost-effectiveness analysis for CRT-P devices compared to CRT-D devices from a German payer’s perspective.

Methods

Longitudinal health claims data from 3569 patients with de novo CRT implantation from 2014 to 2019 were used to parametrise a cohort Markov model. Model outcomes were costs and effectiveness measured in terms of life years. Transition probabilities were derived from multivariable parametric survival regression that controlled for baseline differences of CRT-D and CRT-P patients. Deterministic and probabilistic sensitivity analyses were conducted.

Results

The Markov model predicted a median survival of 84 months for CRT-P patients and 92 months for CRT-D patients. In the base case, CRT-P devices incurred incremental costs of € − 13,093 per patient and 0.30 incremental life years were lost. The ICER was € 43,965 saved per life year lost. In the probabilistic sensitivity analysis, uncertainty regarding the effectiveness was observed but not regarding costs.

Conclusion

This modelling study illustrates the uncertainty of the higher effectiveness of CRT-D devices compared to CRT-P devices. Given the difference in incremental costs between CRT-P and CRT-D treatment, there would be significant potential cost savings to the healthcare system if CRT-D devices were restricted to patients likely to benefit from the additional defibrillator.
Quality of life and symptom burden in children with neurodegenerative diseases: using PedsQL and SProND, a new symptom-based scale
Authors: Chiu Annie Ting Gee , Wong Sheila Suet Na , Wong Naomi Wing Tung , Wong Wilfred Hing Sang , Tso Winnie Wan Yee , Fung Cheuk Wing
Published: September 2022

Background

Children with neurodegenerative conditions (CNDC) often suffer from severe neurodisability and high symptom burden with multisystemic involvement. However, their symptom burden and health-related quality of life (HRQOL) is not systematically documented in the literature, and there is no existing tool for such purposes. We designed our own tool for scoring of symptom burden amongst CNDCs and adopted the PedsQL generic score 4.0 to quantify the impact of overall symptom burden on children’s overall HRQOL.

Methods

The Symptom Profile for children with neurodegnerative condition (SProND) questionnaire was developed, which consisted of 14 questions grouped according to 5 categories, namely epilepsy, neurobehavioural, movement and mobility related, breathing and swallowing, and other daily activities. CNDCs were recruited during visits to the Comprehensive Neurometabolic / Neurodegenerative Program of the Duchess of Kent Children’s Hospital and Hong Kong Children’s Hospital between November 2019 and March 2020. The SProND and PedsQL 4.0 Generic Core Scales were distributed to consenting parents of CNDCs.

Results

36 CNDCs were recruited and matched with community controls. The response rate of subject and control were 99.5% and 98.7% respectively. The Cronbach alpha was 0.61 for the neurobehavioural domain and >  = 0.7 for other domains. The greater number of symptoms each subject experiences, the worse his/ her PedsQL scores. Subjects displaying hypersalivation and swallowing difficulties had average physical health summary scores of less than 30% compared with subjects without these symptoms. On the other hand, average psychosocial health summary scores of subjects with involuntary movements, joint stiffness, hypersalivation, sleep problem and anorexia were approximately 70% compared to subjects without these symptoms.

Discussion and conclusion

This is one of the first studies to look at CNDCs as a group. We propose the SProND questionnaire for evaluation of symptom profile amongst CNDCs with satisfactory internal and external validity. It demonstrates how physical symptoms impact both physical and psychosocial HRQOL, and the cumulative effect of individual symptoms on the overall HRQOL. As such, CNDCs should be systematically screened for multi-systemic symptoms as a routine part of their clinical care, and care plans should be individually catered to individual patients’ symptom burden and specific needs.
Galactose epimerase deficiency: lessons from the GalNet registry
Authors: Derks Britt , Demirbas Didem , Arantes Rodrigo R. , Banford Samantha , Burlina Alberto B. , Cabrera Analía , Chiesa Ana , Couce M. Luz , Dionisi-Vici Carlo , Gautschi Matthias , Grünewald Stephanie , Morava Eva , Möslinger Dorothea , Scholl-Bürgi Sabine , Skouma Anastasia , Stepien Karolina M. , Timson David J. , Berry Gerard T. , Rubio-Gozalbo M. Estela
Published: September 2022

Background

Galactose epimerase (GALE) deficiency is a rare hereditary disorder of galactose metabolism with only a few cases described in the literature. This study aims to present the data of patients with GALE deficiency from different countries included through the Galactosemia Network to further expand the existing knowledge and review the current diagnostic strategy, treatment and follow-up of this not well characterized entity.

Methods

Observational study collecting medical data from December 2014 to April 2022 of 22 not previously reported patients from 14 centers in 9 countries. Patients were classified as generalized or non-generalized based on their genotype, enzyme activities in different tissues and/or clinical picture and professional judgment of the treating physician.

Results

In total 6 patients were classified as generalized and 16 as non-generalized. In the generalized group, acute neonatal illness was reported in 3, cognitive and developmental delays were present in 5 and hearing problems were reported in 3. Four generalized patients were homozygous for the genetic variant NM_001008216.2:c.280G > A (p.Val94Met). In the non-generalized group, no clearly related symptoms were found. Ten novel genetic variants were reported in this study population.

Conclusion

The phenotypic spectrum of GALE deficiency ranges from asymptomatic to severe. The generalized patients have a phenotype that is in line with the 9 described cases in the literature and prescribing dietary interventions is the cornerstone for treatment. In the non-generalized group, treatment advice is more difficult. To be able to offer proper counseling, in addition to red blood cell enzyme activity, genetic studies, transferrin glycoform analysis and enzymatic measurements in fibroblasts are recommended. Due to lack of facilities, additional enzymatic testing is not common practice in many centers nor a tailored long-term follow-up is performed.
How are hygiene programmes designed in crises? Qualitative interviews with humanitarians in the Democratic Republic of the Congo and Iraq
Authors: White Sian , Heath Thomas , Mutula Anna C. , Dreibelbis Robert , Palmer Jennifer
Published: September 2022

Background

Hygiene behaviour change programmes are complex to design. These challenges are heightened during crises when humanitarian responders are under pressure to implement programmes rapidly despite having limited information about the local situation, behaviours and opinions—all of which may also be rapidly evolving.

Methods

We conducted in-depth interviews with 36 humanitarian staff involved in hygiene programme design in two crisis-affected settings—one a conflict affected setting (Iraq) and the other amid a cholera outbreak (Democratic Republic of the Congo). Interviews explored decision-making in each phase of the humanitarian project cycle and were thematically analysed.

Results

Participants considered the design and implementation of hygiene programmes in crises to be sub-optimal. Humanitarians faced sector-specific challenges as well as more general constraints associated with operating within the humanitarian system. Programme-design decisions were made naturalistically and relied heavily on the intuitions and assumptions of senior staff. National organisations were often side-lined from programme design processes despite being in a better position to gather situational data. Consequently, programme design and decision-making processes adopted by humanitarians were similar across the two settings studied and led to similar types of hygiene promotion activities being delivered.

Conclusion

Hygiene programming in crises-affected settings could be strengthened by initiatives targeted at supporting humanitarian staff during the pre-implementation programme design phase. This may include rapid assessment tools to better understand behavioural determinants in crisis-affected contexts; the use of a theory of change to inform the selection of programme activities; and funding mechanisms which encourage equitable partnerships, phased programming, regular adaptation and have programmatic components targeted at sustainability and sector capacity building. Initiatives aimed at sector reform should be cognisant of inter and intra-organisational dynamics, the ways that expertise is created and valued by the sector, and humanitarian habits and norms that arise in response to system constraints and pressures. These micro-organisational processes affect macro-level outcomes related to programme quality and acceptability and determine or limit the roles of national actors in programme design processes.
Development of the Mental Health Peer Support Questionnaire in colleges and vocational schools in Singapore
Authors: Ma QianHui , Gallo Joseph J. , Parisi Jeanine M. , Joo Jin Hui
Published: September 2022

Background

A nation-wide mental health peer support initiative was established in college and vocational schools in Singapore. The purpose of this cross-sectional study was to develop and validate a 20-item self-report instrument, the Mental Health Peer Support Questionnaire (MHPSQ), to assess young adults’ perceived knowledge and skills in mental health peer support.

Methods

We administered the questionnaire to 102 students who were trained as peer supporters, and 306 students who were not trained as peer supporters (denoted as non-peer supporters), in five college and vocational schools. Exploratory factor analysis and descriptive statistics were conducted. Cronbach’s α was used to assess reliability, and independent sample t-tests to assess criterion validity.

Results

Exploratory factor analysis indicated a three-factor structure with adequate internal reliability (discerning stigma [α = .76], personal mastery [α = .77], skills in handling challenging interpersonal situations [α = .74]; overall scale [α = .74]). Consistent with establishing criterion validity, peer supporters rated themselves as significantly more knowledgeable and skilled than non-peer supporters on all items except two: (1) letting peer support recipients make their own mental health decisions, and (2) young adults’ self-awareness of feeling overwhelmed. Peer supporters who had served the role for a longer period of time had significantly higher perceived awareness of stigma affecting mental health help-seeking. Peer supporters who had reached out to more peer support recipients reported significantly higher perceived skills in handling challenging interpersonal situations, particularly in encouraging professional help-seeking and identifying warning signs of suicide.

Conclusions

The MHPSQ may be a useful tool for obtaining a baseline assessment of young adults’ perceived knowledge and skills in mental health peer support, prior to them being trained as peer supporters. This could facilitate tailoring of training programs based on young adults’ initial understanding of mental health peer support. Subsequent to young adults’ training and application of skills, the MHPSQ could also be applied to evaluate the effectiveness of peer programs and mental health training.
Epidemiology and associated factors of depression among cancer patients in Ethiopia: protocol for systematic review and meta-analysis
Authors: Tsehay Mekonnen , Belete Asmare , Necho Mogesie
Published: September 2022

Background

There is no pooled evidence regarding the prevalence and potential associated factors of depression among cancer patients in Ethiopian community. Hence, the current review aimed to examine the prevalence and associated factors of depression among cancer patients in Ethiopia.

Method

A computerized systematic literature search was made in MEDLINE, Scopus, PubMed, Science Direct, and Google Scholar. Each database was searched from its start date to June 2020. More over we will also add scholars and gray literature consultations. All articles will be included if they were published in English, which evaluated the prevalence and associated factors of depression among cancer patients in Ethiopia. Pooled estimations with a 95% confidence interval (CI) were calculated with DerSimonian-Laird random-effects model. Publication bias was evaluated by using inspection of funnel plots and statistical tests.

Discussion

Since we are using existing anonymized data, ethical approval is not required for this study. Our results can be used to guide clinical decisions about the most efficient way to prevent and treat depression among cancer patients.

Systematic review registration Submitted to Prospero.
The neuronal protein Neuroligin 1 promotes colorectal cancer progression by modulating the APC/β-catenin pathway
Authors: Pergolizzi Margherita , Bizzozero Laura , Maione Federica , Maldi Elena , Isella Claudio , Macagno Marco , Mariella Elisa , Bardelli Alberto , Medico Enzo , Marchiò Caterina , Serini Guido , Di Nicolantonio Federica , Bussolino Federico , Arese Marco
Published: September 2022

Background

Colorectal cancer (CRC) remains largely incurable when diagnosed at the metastatic stage. Despite some advances in precision medicine for this disease in recent years, new molecular targets, as well as prognostic/predictive markers, are highly needed. Neuroligin 1 (NLGN1) is a transmembrane protein that interacts at the synapse with the tumor suppressor adenomatous polyposis Coli (APC), which is heavily involved in the pathogenesis of CRC and is a key player in the WNT/β-catenin pathway.

Methods

After performing expression studies of NLGN1 on human CRC samples, in this paper we used in vitro and in vivo approaches to study CRC cells extravasation and metastasis formation capabilities. At the molecular level, the functional link between APC and NLGN1 in the cancer context was studied.

Results

Here we show that NLGN1 is expressed in human colorectal tumors, including clusters of aggressive migrating (budding) single tumor cells and vascular emboli. We found that NLGN1 promotes CRC cells crossing of an endothelial monolayer (i.e. Trans-Endothelial Migration or TEM) in vitro, as well as cell extravasation/lung invasion and differential organ metastatization in two mouse models. Mechanistically, NLGN1 promotes APC localization to the cell membrane and co-immunoprecipitates with some isoforms of this protein stimulates β-catenin translocation to the nucleus, upregulates mesenchymal markers and WNT target genes and induces an “EMT phenotype” in CRC cell lines

Conclusions

In conclusion, we have uncovered a novel modulator of CRC aggressiveness which impacts on a critical pathogenetic pathway of this disease, and may represent a novel therapeutic target, with the added benefit of carrying over substantial knowledge from the neurobiology field.
Clinical analysis of bronchoscope diagnosis and treatment for airway foreign body removal in pediatric patients
Authors: Han Lin-Lin , Meng Chen , Zhang Zhong-Xiao , Tang Xiao-Di , Ma Jing , Li Chang-Xiao
Published: September 2022

Background

Along with the wide spread application and technical development of the flexible and rigid bronchoscopy, the airway foreign body removing method cme to the specific technique for different foreign bodies from the single foreign body forceps.

Methods

Selected 633 children who were diagnosed as airway foreign bodies by the Department of Respiratory Intervention, Children's Hospital affiliated to Shandong University from January 1st, 2018 to December 31st, 2021, and the airway foreign bodies were diagnosed using bronchoscopy. After comprehensive assessment of the foreign body nature in the airway, the foreign bodies were removed by freezing, laser, electrocoagulation, balloon and other techniques, the success rate of the foreign body removed from the airway was observed, the percentage of the foreign body removed using different techniques, the operation time, and the incidence of post-adverse reactions during operation.

Results

The success rate using flexible bronchoscope alone to remove foreign bodies in the airway was 99.2%. After flexible bronchoscopy, 19 cases of foreign bodies were removed by vacuum suction alone, 513 cases were removed by foreign body forceps alone, 62 cases were combined with cryotherapy, 2 cases were electrocoagulation, 6 cases were mesh baskets, 3 cases were balloons, 5 cases were laser, and various 18 cases of foreign bodies were invloved by technical combination. 5 cases of flexible bronchoscope combined with rigid bronchoscope combined to remove foreign bodies. The operation time was from 5 min to 1 h, with an average of 20 min. There were 17 cases of hypoxemia (2.7%) during operation, 36 cases (5.7%) of bleeding caused by airway mucosa injury after treatment, and 70 cases (11.2%) of laryngeal edema. The total incidence of adverse reactions was 19.6%, there were no deaths due to foreign bodies and treatment.

Conclusions

According to different properties of airway foreign bodies, it is safe and effective to select appropriate techniques to remove foreign bodies using the flexible bronchoscope, which can increase the removal rate of airway foreign bodies and reduce the occurrence of serious complications.
Attitudes toward preimplantation genetic testing and quality of life among individuals with hereditary diffuse gastric cancer syndrome
Authors: Shah Ibrahim H. , Salo-Mullen Erin E. , Amoroso Kimberly A. , Kelsen David , Stadler Zsofia K. , Hamilton Jada G.
Published: September 2022

Background

Hereditary Diffuse Gastric Cancer (HDGC) syndrome is an autosomal dominant hereditary cancer predisposition associated with germline pathogenic/likely pathogenic variants in theCDH1gene. Identifying early stage HDGC is difficult, and prophylactic measures can be effective in preventing incidence. Preimplantation Genetic Testing (PGT) can provide information aboutCDH1variant status, HDGC risk, and limit familial transmission ofCDH1variants. To date, however, little is known about the attitudes of individuals withCDH1variants towards PGT.

Methods

Given that little is known about the reproductive attitudes of individuals with HDGC, we recruited participants withCDH1variants from a familial gastric cancer registry and administered a cross-sectional survey with open- and closed-ended response items. We assessed attitudes regarding PGT and the effect of HDGC on quality of life.

Results

Participants (n = 21) were predominantly partnered (61.9%), had a personal cancer history (71.4%), and had biological children (71.4%). Interest in learning about PGT was high; 66.7% of participants were interested in PGT and 90.5% approved of healthcare providers discussing PGT with individuals withCDH1variants. Attitudes regarding personal use were varied. Among all participants, 35% would not, 25% were uncertain, and 40% would use PGT. Personal philosophy and preferences for family and reproduction were key factors related to PGT attitudes. HDGC had moderate effects on participants’ quality of life, including social relationships, health behaviors, and emotional experiences including worry about cancer risk and guilt regarding familial implications.

Conclusion

PGT was identified by participants as acceptable for use in a variety of contexts and benefits of reproductive counseling involving PGT may extend beyondCDH1carriers to family members’ reproductive behaviors. Dispositions towards PGT are governed by personal philosophy or belief systems. These findings can help guide providers counseling individuals withCDH1variants.
Rehabilitation therapy for a severe case of coronavirus disease 2019: a case report
Authors: Takekawa Toru , Kashiwabara Kazumi , Yamada Naoki , Watanabe Shu , Hama Midori , Hashimoto Gentaro , Abo Masahiro , Shinfuku Kyota
Published: September 2022

Background

Patients with severe coronavirus disease 2019 (COVID-19) infection require a long period of time to return to work and society due to significant physical weakness even after recovery. Here we report a patient with a history of nephrectomy who developed severe COVID-19 infection associated with muscle weakness but was able to return to society after rehabilitation therapy.

Case presentation

A Japanese man in his 40s was admitted to the hospital with PCR-based COVID-19 diagnosis. The respiratory condition worsened rapidly and was treated with extracorporeal membrane-assisted ventilation in the intensive case unit. On admission to the Rehabilitation Department on day T + 30 [T: day patient became febrile (38 °C)], he was unable to stand for a long time and used a walker. Rehabilitation therapy was postponed to prevent COVID-19 spread, but the patient was encouraged to exercise during isolation to improve trunk and lower extremity muscle strength. Physical therapy commenced on day T + 49 to improve gait and trunk and lower limb muscle strength. He was able to walk independently and later returned to work following discharge on day T + 53. A computed tomography scan showed an increase in psoas muscle volume from 276 before to 316 cm3after physical therapy, together with a decrease in whole-body extracellular water:total body weight ratio from 0.394 to 0.389.

Conclusions

We have described the beneficial effects of rehabilitation therapy in a patient with severe COVID-19 infection. In addition to exercise, we believe that nutrition is even more important in increasing skeletal muscle mass. Rehabilitation therapy is recommended to enhance the return of severely ill COVID-19 patients to routine daily activity.
Transcatheter arterial embolization for hemothorax caused by spinal fracture without arterial injury: a case report and review of the literature
Authors: Matsunaga Naoki , Okada Takuya , Ono Yuko , Matsushiro Keigo , Sasaki Koji , Gentsu Tomoyuki , Ueshima Eisuke , Sofue Keitaro , Yamaguchi Masato , Sugimoto Koji , Murakami Takamichi
Published: September 2022

Background

Spinal fractures rarely cause hemothorax, and no treatment consensus has been reached. Conservative treatment is generally selected in cases without arterial injury, but there have been some reports of uncontrolled bleeding. Here we report a case of hemothorax caused by spinal fracture without arterial injury treated with transcatheter arterial embolization.

Case presentation

An 88-year-old Japanese woman with back pain was diagnosed with hemothorax due to bleeding from an unstable fracture of the tenth thoracic vertebra. Contrast-enhanced computed tomography revealed no obvious arterial injury. We performed transcatheter arterial embolization of the bilateral tenth intercostal arteries to prevent rebleeding. The hemothorax did not worsen until surgical spinal fixation 9 days post-transcatheter arterial embolization, and she was discharged 30 days after admission.

Conclusion

Transcatheter arterial embolization for hemothorax caused by spinal fractures without obvious arterial injury may be a useful bridge to spinal fixation.
Knockdown of CDC20 promotes adipogenesis of bone marrow-derived stem cells by modulating β-catenin
Authors: Du Yangge , Liu Yunsong , Zhou Yongsheng , Zhang Ping
Published: September 2022

Background

Bone is a rigid organ that provides physical protection and support to vital organs of the body. Bone loss disorders are commonly associated with increased bone marrow adipose tissue. Bone marrow mesenchymal stromal/stem cells (BMSCs) are multipotent progenitors that can differentiate into osteoblasts, adipocytes, and chondrocytes. Cell division cycle 20 (CDC20) is a co-activator of anaphase promoting complex/cyclosome (APC/C), and is required for ubiquitin ligase activity. Our previous study showed that CDC20 promoted the osteogenic commitment of BMSCs and Cdc20 conditional knockout mice suggested a decline in bone mass. In this study, we found that knockdown of CDC20 promoted adipogenic differentiation of BMSCs by modulating β-catenin, which suggested a link between adipogenesis and osteogenesis.

Methods

Lentivirus containing a CDC20 shRNA was used for CDC20 knockdown in human BMSCs (hBMSCs). Primary mouse BMSCs (mBMSCs) were isolated from Cdc20f/f and Sp7-Cre;Cdc20f/f mice. Adipogenesis was examined using quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting analysis of adipogenic regulators, Oil Red O staining, and transplantation into nude mice. CDC20 knockout efficiency was determined through immunochemistry, qRT-PCR, and western blotting of bone marrow. Accumulation of adiposity was measured through histology and staining of bone sections. Exploration of the molecular mechanism was determined through western blotting, Oil Red O staining, and qRT-PCR.

Results

CDC20 expression in hBMSCs was significantly decreased during adipogenic differentiation. CDC20 knockdown enhanced hBMSC adipogenic differentiation in vitro. CDC20-knockdown hBMSCs showed more adipose tissue-like constructs upon hematoxylin and eosin (H&E) and Oil Red O staining. Sp7-Cre;Cdc20f/f mice presented increased adipocytes in their bone marrow compared with the control mice. mBMSCs from Sp7-Cre;Cdc20f/f mice showed upregulated adipogenic differentiation. Knockdown of CDC20 led to decreased β-catenin levels, and a β-catenin pathway activator (lithium chloride) abolished the role of CDC20 in BMSC adipogenic differentiation.

Conclusions

Our findings showed that CDC20 knockdown enhanced adipogenesis of hBMSC and mBMSCs adipogenesis in vitro and in vivo. CDC20 regulates both adipogenesis and osteogenesis of BMSCs, and might lead to the development of new therapeutic targets for “fatty bone” and osteoporosis.
The optimal transplantation strategy of umbilical cord mesenchymal stem cells in spinal cord injury: a systematic review and network meta-analysis based on animal studies
Authors: Lu Yubao , Zhang Wei , Tian Zhenming , Liang Qian , Liu Chenrui , Wu Yingjie , Zhang Liangming , Rong Limin
Published: September 2022

Objective

Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal transplantation strategy are still unclear. Therefore, exploring the optimal treatment strategy of UCMSCs in animal studies by systematic review can provide reference for the development of animal studies and clinical research in the future.

Methods

Databases of PubMed, Ovid-Embase, Web of Science, CNKI, WanFang, VIP, and CBM were searched for the literature in February 11, 2022. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction.

Results and Discussion

A total of 40 animal studies were included for combined analysis. In different subgroups, the results of traditional meta-analysis and network meta-analysis were consistent, that is, the therapeutic effect of high-dose (≥ 1 × 106) transplantation of UCMSCs was significantly better than that of low dose (< 1 × 106), the therapeutic effect of local transplantation of UCMSCs was significantly better than that of intravenous transplantation, and the therapeutic effect of subacute transplantation of UCMSCs was significantly better than that of acute and chronic transplantation. However, in view of the inherent risk of bias and limited internal and external validity of the current animal studies, more high-quality, direct comparison studies are needed to further explore the optimal transplantation strategy for UCMSCs in the future.
Characterizing the secretome of licensed hiPSC-derived MSCs
Authors: Ramos Yolande F. M. , Tertel Tobias , Shaw Georgina , Staubach Simon , de Almeida Rodrigo Coutinho , Suchiman Eka , Kuipers Thomas B. , Mei Hailiang , Barry Frank , Murphy Mary , Giebel Bernd , Meulenbelt Ingrid
Published: September 2022

Although mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. RNA sequencing confirmed high resemblance, with average Pearson correlation of 0.88 and Jaccard similarity index of 0.99, and similar to hBMSCs the hiMSCs released extracellular vesicles with in vitro immunomodulatory properties. Potency assay with TNFα and IFNγ demonstrated an increase in well-known immunomodulatory genes such as IDO1, CXCL8/IL8, and HLA-DRA which was also highlighted by enhanced secretion in the media. Notably, expression of 125 genes increased more than 1000-fold. These genes were predicted to be regulated by NFΚB signaling, known to play a central role in immune response. Altogether, our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.
Therapeutic potential of conditioned medium obtained from deferoxamine preconditioned umbilical cord mesenchymal stem cells on diabetic nephropathy model
Authors: Ozkan Serbay , Isildar Basak , Ercin Merve , Gezginci-Oktayoglu Selda , Konukoglu Dildar , Neşetoğlu Neşet , Oncul Mahmut , Koyuturk Meral
Published: September 2022

Background

The therapeutic potential of mesenchymal stem cells (MSCs)-derived conditioned media (CM) can be increased after preconditioning with various chemical agents. The aim of this study is comparative evaluation of effects of N-CM and DFS-CM which are collected from normal (N) and deferoxamine (DFS) preconditioned umbilical cord-derived MSCs on rat diabetic nephropathy (DN) model.

Methods

After incubation of the MSCs in serum-free medium with/without 150 µM DFS for 48 h, the contents of N-CM and DFS-CM were analyzed by enzyme-linked immunosorbent assay. Diabetes (D) was induced by single dose of 55 mg/kg streptozotocin. Therapeutic effects of CMs were evaluated by biochemical, physical, histopathological and immunohistochemical analysis.

Results

The concentrations of vascular endothelial growth factor alpha, nerve growth factor and glial-derived neurotrophic factor in DFS-CM increased, while one of brain-derived neurotrophic factor decreased in comparison with N-CM. The creatinine clearance rate increased significantly in both treatment groups, while the improvement in albumin/creatinine ratio and renal mass index values were only significant for D + DFS-CM group. Light and electron microscopic deteriorations and loss of podocytes-specific nephrin and Wilms tumor-1 (WT-1) expressions were significantly restored in both treatment groups. Tubular beclin-1 expression was significantly increased for DN group, but it decreased in both treatment groups. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cell death increased in the tubules of D group, while it was only significantly decreased for D + DFS-CM group.

Conclusions

DFS-CM can be more effective in the treatment of DN by reducing podocyte damage and tubular apoptotic cell death and regulating autophagic activity with its more concentrated secretome content than N-CM.

Graphical Abstract
Stable expression of a truncated TLX variant drives differentiation of induced pluripotent stem cells into self-renewing neural stem cells for production of extracellular vesicles
Authors: Xu Mingzhi , Chen Gang , Dong Yanan , Xiang Shensi , Xue Miaomiao , Liu Yongxue , Song Haijing , Song Haifeng , Wang Yi
Published: September 2022

Background

Neural stem cells (NSCs)-derived extracellular vesicles (EVs) possess great potential in treating severe neurological and cerebrovascular diseases, as they carry the modulatory and regenerative ingredients of NSCs. Induced pluripotent stem cells (iPSCs)-derived NSCs culture represents a sustainable source of therapeutic EVs. However, there exist two major challenges in obtaining a scalable culture of NSCs for high-efficiency EVs production: (1) the heterogeneity of iPSC-derived NSCs culture impairs the production of high-quality EVs and (2) the intrinsic propensity of neuronal or astroglial differentiation of NSCs during prolonged culturing reduces the number of NSCs for preparing EVs. A NSCs strain that is amenable to stable self-renewal and proliferation is thus greatly needed for scalable and long-term culture.

Methods

Various constructs of the genes encoding the orphan nuclear receptor NR2E1 (TLX) were stably transfected in iPSCs, which were subsequently cultured in a variety of differentiation media for generation of iNSCsTLX. Transcriptomic and biomarker profile of iNSCsTLXwere investigated. In particular, the positivity ratios of Sox2/Nestin and Musashi/Vimentin were used to gauge the homogeneity of the iNSCsTLXculture. The iNSCs expressing a truncated version of TLX (TLX-TP) was expanded for up to 45 passages, after which its neuronal differentiation potential and EV activity were evaluated.

Results

Stable expression of TLX-TP could confer the iPSCs with rapid and self-driven differentiation into NSCs through stable passaging up to 225 days. The long-term culture of NSCs maintained the highly homogenous expression of NSC-specific biomarkers and potential of neuronal differentiation. EVs harvested from the TLX-expressing NSCs cultures exhibited anti-inflammatory and neuroprotective activities.

Conclusions

iPSC-derived NSCs stably expressing TLX-TP is a promising cell line for scalable production of EVs, which should be further exploited for therapeutic development in neurological treatment.