bluuebunny/crossref_metadata_2025 huggingface dataset:
ecRESCUE: a novel ecDHFR-regulated RESCUE system with reduced RNA off-targeting activity
Authors: Wang Yihan , Li Guo , Li Xiangyang , Wang Yuzhe , Huang Xingxu , Hu Xiaoxiang , Gao Jianen
Published: July 2021

The currently available RESCUE RNA base editing system demonstrates considerable potential for the treatment of genetic diseases at the transcriptional level. However, the relatively high incidence of off-target events hampers the precise RNA editing, thereby limiting its use in the clinical setting. This study describes a new RNA base editing method, named ecRESCUE, which utilizes inducible stabilization of the protein ecDHFR DD fused at the C-terminal of the original RESCUE system. In vitro experiments in 293T cells showed that the ecRESCUE editor markedly reduced the incidence of off-target single nucleotide polymorphisms without affecting the RNA A-to-I and C-to-U base editing efficiency. Altogether, these results demonstrate that the inducible ecRESCUE system represents an attractive approach to regulate and improve the outcome of the available RNA base editor with reduced off-targeting activity.
Emerging trends and focus of human gastrointestinal microbiome research from 2010–2021: a visualized study
Authors: Yuan Xingzhu , Chang Chengting , Chen Xinrong , Li Ka
Published: July 2021

Background

The gastrointestinal microbiome is an important component of the human body and is closely related to human health and disease. This study describes the hotspots of the human gastrointestinal microbiome research and its evolution in the past decade, evaluates the scientific cooperation network, and finally predicts the field’s future development trend using bibliometric analysis and a visualized study.

Methods

We searched the original articles from January 2010 to February 2021 in the Scopus database using the term “gastrointestinal microbiome” and its synonyms. CiteSpace was used to construct country and author co-occurrence map; conduct journal, citation cocitation analysis, and reference co-citation knowledge map; and form a keywords co-occurrence map, a clustering knowledge map, timeline view of keywords, and burst term map.

Result

A total of 4444 documents published from January 2010 to February 2021 were analysed. In approximately the past decade, the number of articles on the human gastrointestinal microbiome has increased rapidly, and the research topics focus on different populations, research methods, and detection methods. All countries and regions in the world, led by the US, are studying the human gastrointestinal microbiome, and many research teams with close cooperation have been formed. The research has been published extensively in microbiology journals and clinical medicine journals, and the highly cited articles mainly describe the relationship between gastrointestinal microorganisms and human health and disease. Regarding the research emphasis, researchers' exploration of the human gastrointestinal microbiome (2011–2013) was at a relatively macro and superficial stage and sought to determine how the gastrointestinal microbiome relates to humans. From 2014 to 2017, increasingly more studies were conducted to determine the interaction between human gastrointestinal flora and various organs and systems. In addition, researchers (2018–2021) focused on the gastrointestinal microbial community and the diversity of certain types of microbes.

Conclusion

Over time, the scope of the research on the clinical uses of the gastrointestinal microbiome gradually increased, and the contents were gradually deepened and developed towards a more precise level. The study of the human gastrointestinal microbiome is an ongoing research hotspot and contributes to human health.
Cancer-associated fibroblast infiltration in gastric cancer: the discrepancy in subtypes pathways and immunosuppression
Authors: Liu Xu , Yao Li , Qu Jingkun , Liu Lin , Lu Ning , Wang Jiansheng , Zhang Jia
Published: July 2021

Background

General role of cancer-associated fibroblast (CAF) and its infiltration characteristics in gastric cancer remains to be unknown.

Methods

We estimate CAF infiltration in bulk tumor tissue with RNA-seq data and analyzed its relationship with gastric cancer subtype, survival and immune microenvironment.

Results

We revealed CAF intend to have higher infiltration in diffuse, genomically stable, and advanced gastric cancer. CAF is associated with immunosuppressive microenvironment. Wide transcriptomics alterations occur in high CAF infiltrated gastric cancer, PI3K/AKT, TGFB and Hedgehog pathway are remarkable in this procedure. We utilized receptor tyrosine kinases and TGFB pathway ligands to construct risk score system that can predict survival.

Conclusion

Thus, CAF is associated with aggressive phenotype of gastric cancer and risk score based on RTK and TGFB pathway ligands expression is a promising tool for assessment of gastric cancer survival.
Differential effects of the cell cycle inhibitor, olomoucine, on functional recovery and on responses of peri-infarct microglia and astrocytes following photothrombotic stroke in rats
Authors: Yew Wai Ping , Djukic Natalia D. , Jayaseelan Jaya S. P. , Woodman Richard J. , Muyderman Hakan , Sims Neil R.
Published: July 2021

Background

Following stroke, changes in neuronal connectivity in tissue surrounding the infarct play an important role in both spontaneous recovery of neurological function and in treatment-induced improvements in function. Microglia and astrocytes influence this process through direct interactions with the neurons and as major determinants of the local tissue environment. Subpopulations of peri-infarct glia proliferate early after stroke providing a possible target to modify recovery. Treatment with cell cycle inhibitors can reduce infarct volume and improve functional recovery. However, it is not known whether these inhibitors can influence neurological function or alter the responses of peri-infarct glia without reducing infarction. The present study aimed to address these issues by testing the effects of the cell cycle inhibitor, olomoucine, on recovery and peri-infarct changes following photothrombotic stroke.

Methods

Stroke was induced by photothrombosis in the forelimb sensorimotor cortex in Sprague-Dawley rats. Olomoucine was administered at 1 h and 24 h after stroke induction. Forelimb function was monitored up to 29 days. The effects of olomoucine on glial cell responses in peri-infarct tissue were evaluated using immunohistochemistry and Western blotting.

Results

Olomoucine treatment did not significantly affect maximal infarct volume. Recovery of the affected forelimb on a placing test was impaired in olomoucine-treated rats, whereas recovery in a skilled reaching test was substantially improved. Olomoucine treatment produced small changes in aspects of Iba1 immunolabelling and in the number of CD68-positive cells in cerebral cortex but did not selectively modify responses in peri-infarct tissue. The content of the astrocytic protein, vimentin, was reduced by 30% in the region of the lesion in olomoucine-treated rats.

Conclusions

Olomoucine treatment modified functional recovery in the absence of significant changes in infarct volume. The effects on recovery were markedly test dependent, adding to evidence that skilled tasks requiring specific training and general measures of motor function can be differentially modified by some interventions. The altered recovery was not associated with specific changes in key responses of peri-infarct microglia, even though these cells were considered a likely target for early olomoucine treatment. Changes detected in peri-infarct reactive astrogliosis could contribute to the altered patterns of functional recovery.
miR-3113-5p, miR-223-3p, miR-133a-3p, and miR-499a-5p are sensitive biomarkers to diagnose sudden cardiac death
Authors: Yan Fengping , Chen Yuanyuan , Ye Xing , Zhang Fu , Wang Shiquan , Zhang Le , Luo Xiaoting
Published: July 2021

Background

Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases.

Methods

This study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and gross myocardial scar. Carbon monoxide (CO) intoxication (n = 14) and fatal injury death (n = 14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs.

Results

It showed that heart samples from the SCD-negative autopsy group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, receiver operating characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71–97.06% and specificity of 70–100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, and a combination of two miRNAs presented higher diagnostic value (AUC = 0.7407–0.8667).

Conclusion

miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.
Clinicopathological significance of primitive phenotypes in early gastric cancer with differentiated histology
Authors: Zhou Zhi-Yi , Sun Jie , Guo Qing , Zhao Hai-Bin , Zhou Zhi-Hua
Published: July 2021

Background

Certain gastric cancers exhibit some primitive phenotypes, which may indicate a high malignancy. In histologically differentiated early gastric cancer (EGC), the presence and the clinicopathological significance of the primitive phenotype remain unclear.

Methods

Using immunohistochemical staining we detected the expression of three primitive phenotypic markers SALL4, Glypican-3(GPC3), and AFP in whole tissue sections of differentiated EGC (gastrectomy specimens, n = 302). For those cases with primitive phenotypes, we analyzed their clinicopathological features and evaluated whether the criteria for endoscopic resection were met.

Results

We found that 9.3% (28/302) of all differentiated EGC cases have primitive phenotypes, and most of these cases (25/28) exhibit a histomorphology similar to conventional differentiated EGC. Patients with primitive phenotypes had a deeper invasion, a higher rate of ulcer and lymphatic invasion than cases without primitive phenotype. Moreover, patients with primitive phenotypes displayed a significantly higher frequency of LNM than those without (57.1% vs 8.8%, P < 0.001). Multivariate analysis revealed that presence of primitive phenotypes was an independent risk factor for LNM (P = 0.001, HR 6.977, 95% CI: 2.199–22.138). Interestingly, we found 2 cases with primitive phenotypes developed LNM, and they both met the expanded indications of endoscopic resection for differentiated EGC.

Conclusions

A small number of differentiated EGC have primitive phenotypes, which were closely related to LNM and were an independent risk factor for LNM. Given its highly aggressive behavior, differentiated EGC with primitive phenotypes should be evaluated with stricter criteria before endoscopic resection, or considered to give an additional surgical operation after endoscopic resection.
Barriers and facilitators to shared decision-making in hospitals from policy to practice: a systematic review
Authors: Waddell Alex , Lennox Alyse , Spassova Gerri , Bragge Peter
Published: July 2021

Background

Involving patients in their healthcare using shared decision-making (SDM) is promoted through policy and research, yet its implementation in routine practice remains slow. Research into SDM has stemmed from primary and secondary care contexts, and research into the implementation of SDM in tertiary care settings has not been systematically reviewed. Furthermore, perspectives on SDM beyond those of patients and their treating clinicians may add insights into the implementation of SDM. This systematic review aimed to review literature exploring barriers and facilitators to implementing SDM in hospital settings from multiple stakeholder perspectives.

Methods

The search strategy focused on peer-reviewed qualitative studies with the primary aim of identifying barriers and facilitators to implementing SDM in hospital (tertiary care) settings. Studies from the perspective of patients, clinicians, health service administrators, and decision makers, government policy makers, and other stakeholders (for example researchers) were eligible for inclusion. Reported qualitative results were mapped to the Theoretical Domains Framework (TDF) to identify behavioural barriers and facilitators to SDM.

Results

Titles and abstracts of 8724 articles were screened and 520 were reviewed in full text. Fourteen articles met inclusion criteria. Most studies (n = 12) were conducted in the last four years; only four reported perspectives in addition to the patient-clinician dyad. In mapping results to the TDF, the dominant themes were Environmental Context and Resources, Social/Professional Role and Identity, Knowledge and Skills, and Beliefs about Capabilities. A wide range of barriers and facilitators across individual, organisational, and system levels were reported. Barriers specific to the hospital setting included noisy and busy ward environments and a lack of private spaces in which to conduct SDM conversations.

Conclusions

SDM implementation research in hospital settings appears to be a young field. Future research should build on studies examining perspectives beyond the clinician-patient dyad and further consider the role of organisational- and system-level factors. Organisations wishing to implement SDM in hospital settings should also consider factors specific to tertiary care settings in addition to addressing their organisational and individual SDM needs.

Trial Registration

The protocol for the review is registered on the Open Science Framework and can be found at https://osf.io/da645/, DOI 10.17605/OSF.IO/DA645.
Incorporation of an intercostal catheter into a multimodal analgesic strategy for uniportal video-assisted thoracoscopic surgery: a feasibility study
Authors: Tan Jian Wei , Mohamed Jameelah Sheik , Tam John Kit Chung
Published: July 2021

Background

Well-controlled postoperative pain is essential for early recovery after uniportal video-assisted thoracoscopic surgery (UVATS). Conventional analgesia like opioids and thoracic epidural anaesthesia have been associated with hypotension and urinary retention. Intercostal catheters are a regional analgesic alternative that can be inserted during UVATS to avoid these adverse effects. This feasibility study aims to evaluate the postoperative pain scores and analgesic requirements with incorporation of an intercostal catheter into a multimodal analgesic strategy for UVATS.

Methods

In this observational study, 26 consecutive patients who underwent UVATS were administered a multilevel intercostal block and oral paracetamol. All of these patients received 0.2% ropivacaine continuously at 4 ml/h via an intercostal catheter at the level of the incision. Rescue analgesia including etoricoxib, gabapentin and opioids were prescribed using a pain ladder approach. Postoperative pain scores and analgesic usage were assessed. The secondary outcomes were postoperative complications, days to ambulation and length of stay.

Results

No technical difficulties were encountered during placement of the intercostal catheter. There was only one case of peri-catheter leakage. Mean pain score was 0.31 (range 0–2) on post-operative day 1 and was 0.00 by post-operative day 5. 16 patients (61.6%) required only oral rescue analgesia. The number of patients who required rescue non-opioids only increased from 1 in the first 7 months to 8 in the next 7 months. There were no cases of hypotension or urinary retention. Median time to ambulation was 1 day (range 1–2). Mean post-operative length of stay was 4.17 ± 2.50 days.

Conclusions

Incorporation of an intercostal catheter into a multimodal analgesia strategy for UVATS is feasible and may provide adequate pain control with decreased opioid usage.
An extremely rare case of Rosai–Dorfman disease in the thymus
Authors: Shen Cheng , Liao Hu
Published: July 2021

Background

There were very few reports of Rosai–Dorfman disease in the thymus, which known as sinus histiocytosis with massive lymphadenopathy. It usually accompanied with other systemic symptoms such as fever, malaise, night sweats, or weight loss in the short term.

Case presentation

We herein report a rare case of RDD of thymic origin and a review of the literature concerning the clinical and pathological features of this disease, which is often misdiagnosed as thymoma. The patient was underwent thymectomy to extirpate the lesion completely by video-assisted thoracic surgery.

Conclusions

To the best of our knowledge, this is the fourth thymus occurring RDD case with proof via histology and IHC. Our findings suggest the difficulty of making a diagnosis before surgery and more cases will need to be reported in order to facilitate the preoperative diagnosis of such a rare tumor.
Three-dimensional transesophageal echocardiography in diagnosis of intermediate atrioventricular septal defect in the adult: case report and literature review
Authors: Schusterova Ingrid , Jakubova Marta , Vachalcova Marianna , Sieradzka Karolinska , Gibarty Claudia , Poruban Tibor , Gasparovic Ivo , Artemiou Panagiotis
Published: July 2021

Background

Intermediate type atrioventricular septal defect is less frequent than complete or partial atrioventricular septal defect, and is rarely encountered in the elderly and the utility of three dimensional transesophageal echocardiography in the diagnosis has not been reported to date.

Case presentation

In this case report, we described a rare case of an intermediate atrioventricular septal defect in an adult patient and we showed the valuable utility of real time 3D transesophageal echocardiography in the diagnosis and future surgical planning. The patient was referred to a tertiary center for an elective surgical repair. Finally, we provided a detailed review of the literature concerning the intermediate type of atrioventricular septal defect.

Conclusion

Although 2D transthoracic and transesophageal echocardiography enables diagnosis of the intermediate type atrioventricular septal defect, precise assessment of anatomy of atrioventricular septal defects and common atrioventricular valve was enabled only by real time 3D echocardiography.
Health Disparities among adults cared for at an urban cystic fibrosis program
Authors: DiMango Emily , Simpson Kaitlyn , Menten Elizabeth , Keating Claire , Fan Weijia , Leu Cheng-Shiun
Published: July 2021

Background

Evidence is conflicting regarding differential health outcomes in racial and ethnic minorities with cystic fibrosis (CF), a rare genetic disease affecting approximately 28,000 Americans. We performed a cross-sectional analysis of health outcomes in Black/Latinx patients compared with non-Hispanic Caucasian patients cared for in a CF center in New York City. Adult patients enrolled in the CF Foundation Patient Registry at the Columbia University Adult CF Program and seen at least once during 2019 were included. Health metrics were compared between Black/Latinx and non-Hispanic Caucasian patients.

Results

262 patients were eligible. 39 patients (15%) identified as Black/Latinx or non-Hispanic Caucasian. Descriptive statistics are reported with mean (standard deviation). Current age was 35.9 (13.3) years for non-Hispanic Caucasian and 32.0 (9.3) years for Black/Latinx patients (p = 0.087). Age of diagnosis did not differ between groups; 9.56 (15.96) years versus 11.59 (15.8) years for non-Hispanic Caucasian versus Black/Latinx respectively (p = 0.464). Pulmonary function, measured as mean forced expiratory volume in one second (FEV1) was 70.6 (22.5) percent predicted in non-Hispanic Caucasian versus 59.50 (27.9) percent predicted in Black/Latinx patients (p = 0.010). Number of visits to the CF clinic were similar between groups. When controlled for age, gender, co-morbidities, median income, and insurance status, there was a continued association between minority status and lower FEV1.

Conclusions

Minorities with CF have significantly lower pulmonary function, the major marker of survival, than non-Hispanic Caucasians, even when controlled for a variety of demographic and socioeconomic factors that are known to affect health status in CF. Significant health disparities based on race and ethnicity exist at a single CF center in New York City, despite apparent similarities in access to guideline based care at an accredited CF Center. This data confirms the importance of design of culturally appropriate preventative and management strategies to better understand how to direct interventions to this vulnerable population with a rare disease.
The first European consensus on principles of management for achondroplasia
Authors: Cormier-Daire Valerie , AlSayed Moeenaldeen , Ben-Omran Tawfeg , de Sousa Sérgio Bernardo , Boero Silvio , Fredwall Svein O. , Guillen-Navarro Encarna , Irving Melita , Lampe Christian , Maghnie Mohamad , Mortier Geert , Peijin Zagorka , Mohnike Klaus
Published: July 2021

Achondroplasia is the most common type of skeletal dysplasia, caused by a recurrent pathogenic variant in the fibroblast growth factor receptor 3 (FGFR3). The management of achondroplasia is multifaceted, requiring the involvement of multiple specialties across the life course. There are significant unmet needs associated with achondroplasia and substantial differences in different countries with regard to delivery of care. To address these challenges the European Achondroplasia Forum (EAF), a network of senior clinicians and orthopaedic surgeons from Europe and the Middle East representative of the achondroplasia clinical community, came together with the overall aim of improving patient outcomes. The EAF developed a consensus on guiding principles of management of achondroplasia to provide a basis for developing optimal care in Europe. All members of the EAF were invited to submit suggestions for guiding principles of management, which were consolidated and then discussed during a meeting in December 2020. The group voted anonymously on the inclusion of each principle, with the requirement of a 75% majority at the first vote to pass the principle. A vote on the level of agreement was then held. A total of six guiding principles were developed, which cover management over the lifetime of a person with achondroplasia. The principles centre on the lifelong management of achondroplasia by an experienced multidisciplinary team to anticipate and manage complications, support independence, and improve quality of life. There is focus on timely referral to a physician experienced in the management of achondroplasia on suspicion of the condition, shared decision making, the goals of management, access to adaptive measures to enable those with achondroplasia to access their environment, and the importance of ongoing monitoring throughout adolescence and adulthood. All principles achieved the 75% majority required for acceptance at the first vote (range 91–100%) and a high level of agreement (range 8.5–9.6). The guiding principles of management for achondroplasia provide all healthcare professionals, patient advocacy groups and policy makers involved in the management of achondroplasia with overarching considerations when developing health systems to support the management of achondroplasia.
Randomized double blind clinical trial evaluating the Ellagic acid effects on insulin resistance, oxidative stress and sex hormones levels in women with polycystic ovarian syndrome
Authors: Kazemi Mahnaz , Lalooha Fatemeh , Nooshabadi Mohammadreza Rashidi , Dashti Fariba , Kavianpour Maria , Haghighian Hossein Khadem
Published: July 2021

Objective

The design of this study was due to the report of the antioxidant properties of Ellagic acid (EA) for its evaluation on the Insulin resistance (IR), oxidative stress and sex hormones levels in women with polycystic ovarian syndrome (PCOS).

Methods

In this randomized, double-blind, placebo-controlled clinical trial, 60 patients were recruited. Patients were randomly allocated consumed a capsule containing 200 mg of EA per day (n = 30) or placebo (n = 30) for 8 weeks. The fasting blood sugar (FBS), insulin, IR, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), total antioxidant capacity (TAC), Malondialdehyde (MDA), C-reactive protein (CRP), Tumor necrosis factor-alpha (TNF-α), sex hormones and anti-mullerian hormone (AMH) were measured at the beginning and end of the study.

Result

At the end of the study, the mean of FBS, insulin, IR, TC, TG, LDL, MDA, CRP, TNF-α, total testosterone, prolactin and AMH were significantly decreased in the intervention group compared to the placebo group (P < 0.05). Also, there was a significant increase in the mean of TAC after supplementation with EA (P < 0.05). At the end of the study, no significant changes were observed in the mean of anthropometric factors, physical activity and food intake (P > 0.05).

Conclusion

EA supplementation can be helpful as a diet supplement in women with PCOS through improvement in insulin resistance. This supplement may be used to reduce metabolic disorders in women.

Trial registration

This study was retrospectively (07–07-2019) registered in the Iranian website (www.irct.ir) for registration of clinical trials (IRCT20141025019669N12).
Normative data for handgrip strength in Iranian healthy children and adolescents aged 7–18 years: comparison with international norms
Authors: Rostamzadeh Sajjad , Saremi Mahnaz , Abouhossein Alireza , Vosoughi Shahram , Molenbroek Johan F. M.
Published: July 2021

Background

Grip strength is an essential component of physical fitness. The objective of this study was to develop normative handgrip strength data for Iranian healthy boys and girls comparing their handgrip strength with international reference values.

Methods

Handgrip strength was measured in 2637 healthy children/adolescents (1391 boys and 1246 girls), aged 7–18 years, using a standard adjustable Jamar hand dynamometer (Model 5030 J1, Sammons Preston Rolyan, Bolingbrook, IL, USA). Body mass (kg) and stature (cm) were measured and body mass index was computed in kg/m2. The sample was stratified by gender, age, and hand preference.

Results

Handgrip strength increased with age and was considerably higher in boys than in girls for all age groups (p < 0.001). Grip strength had a parallel and linear growth for both genders until the age of about 11 years and showed a steeper upward slope in boys than in girls thereafter. The findings of the current investigation were significantly different from those of the previously published normative data, especially for boys over the age of 12 years and girls in the age range of 7–18 years (p < 0.001). This difference was mainly in such a way that the Iranians had lower handgrip strength.

Conclusions

The differences between present results and those of similar available in the literature in this field emphasize the significant role of using normative data specific to a particular population in research or clinical settings.
Detection of endocrine disorders in young children with multi-transfused thalassemia major
Authors: Mahmoud Ramadan A. , Khodeary Ashraf , Farhan Marwa S.
Published: July 2021

Background

Beta thalassemia major (TM) is the most common inherited genetic disorder worldwide. Patients are at risk of iron overload, which leads to various forms of tissue damage, including endocrinopathies. The aim of this study was to evaluate the prevalence and risk factors of endocrine disorders in young patients with multi-transfused TM receiving iron chelation therapy.

Methods

The inclusion criteria included all known cases of TM according to hemoglobin electrophoresis data, aged 12 years or younger, during the study period. The patient’s age, gender, parent’s consanguinity, clinical examination, and types of iron chelating agents used were recorded. Serum ferritin level, complete blood count (CBC), blood glucose homeostasis, thyroid, and parathyroid functions were determined.

Results

One hundred twenty patients met the inclusion criteria; 70% of them had malnutrition. The presence of endocrine disorders was observed in 28/120 (23.33%) patients. The most common endocrine disorders were thyroid disorders, either subclinical or clinical hypothyroidism in 11/120 (9.17%) patients, followed by abnormalities in glucose homeostasis 9/120 (7.5%). The prevalence of impaired glucose tolerance, impaired fasting glucose, and diabetes mellitus in the present study was 5 (4.17%), 4 (3.33%), and 0 (00%), respectively, while the least frequent endocrine disorder seen in our patients was hypoparathyroidism in 8/120 (6.66%). We noted that high serum ferritin levels and poor patient compliance to therapy were significantly associated with increased endocrine disorders (OR 0.98, 95% CI 0.96–0.99,P = 0.003 and OR 0.38, 95% CI 0.16:0.93,P = 0.03, respectively). Combined chelating iron agents significantly decreased the prevalence of endocrine disorders when compared with monotherapy (OR 0.40, 95% CI 0.16:0.97,P = 0.04).

Conclusion

Endocrine disorders could occur in TM patients early before or equal to 12 years of life in about one-fourth of the patients. A high serum ferritin level and poor patient compliance to therapy were significantly associated with increased endocrine disorders. Combined iron-chelating agents were associated with a decreased prevalence of endocrine disorders when compared with monotherapy.
Assessment of bedside lower limb angiography combined with continuous NIRS monitoring for the detection of lower limb complications of VA-ECMO: an observational monocentric study
Authors: Koszutski Matthieu , Mattei Mathieu , Maureira Juan Pablo , Kimmoun Antoine , Levy Bruno
Published: July 2021

Trial registration: ClinicalTrials.gov Identifier: NCT03910062.
Protocol for the development of a Core Outcome Set for trials on the prevention and treatment of Orthodontically induced enamel White Spot Lesions (COS-OWSL)
Authors: Qin Danchen , Wang Yunlei , Levey Colin , Ngan Peter , He Hong , Hua Fang ,   on behalf of the Core Outcome Set for trials on the prevention and treatment of enamel White Spot Lesions (COS-WSL) group
Published: July 2021

Background

Enamel white spot lesions (WSLs), characterized by an opaque, matt, and chalky white appearance of enamel, are a sign of incipient caries. WSLs are common in orthodontic practice and can affect both the oral health and dental aesthetics of patients. Extensive studies have been conducted to evaluate the effectiveness of prevention or treatment for orthodontically induced enamel WSLs. However, substantial heterogeneity has been found in the outcomes used for the prevention and treatment of WSLs in literature, which prevents researchers from comparing and combining the results of different studies to draw more decisive conclusions. Therefore, we aim to develop a Core Outcome Set for trials on the prevention and treatment of Orthodontically induced enamel White Spot Lesions (COS-OWSL).

Methods

The development of COS-OWSL comprises four phases: (1) a scoping review to identify and summarize all existing outcomes that have been used in trials on the prevention or treatment of orthodontically induced WSLs; (2) qualitative interviews with orthodontic patients without (for prevention) and with WSL-affected teeth (for treatment) and relevant dental professionals to identify additional outcomes relevant to them; (3) Delphi surveys to collect opinions from key stakeholders including patients, dental professionals, and researchers and to reach a preliminary consensus; and (4) a consensus meeting to develop the final COS-OWSL.

Discussion

The COS-OWSL will be developed to facilitate the synthesis of evidence regarding the prevention and treatment of orthodontically induced WSLs and to promote the consistent use of relevant patient-important outcomes among future studies in this field.

Trial registration

Core Outcome Measures in Effectiveness Trials (COMET) initiative (the COS-WSL project) 1399
Effects of an exclusive human-milk diet in preterm neonates on early vascular aging risk factors (NEOVASC): study protocol for a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial
Authors: Mitterer Wolfgang , Binder Christoph , Blassnig-Ezeh Anya , Auer-Hackenberg Lorenz , Berger Angelika , Simma Burkhard , Wald Martin , Lee Martin , Kiechl-Kohlendorfer Ursula
Published: July 2021

Background

Preterm birth accounts for approximately 11% of all livebirths globally. Due to improvements in perinatal care, more than 95% of these infants now survive into adulthood. Research has indicated a robust association between prematurity and increased cardiovascular risk factors and cardiovascular mortality. While the innate adverse effects of prematurity on these outcomes have been demonstrated, therapeutic strategies on the mitigation of these concerning developments are lacking. The primary objective of the NEOVASC clinical trial is therefore to investigate whether the administration of a prolonged exclusive human-milk diet in preterm infants is capable of alleviating the harmful effects of preterm birth on the early development of cardiovascular risk factors.

Methods

The NEOVASC study is a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial conducted in four Austrian tertiary neonatal care facilities. The purpose of the present trial is to investigate the effects of a prolonged exclusive human-milk-diet devoid of bovine-milk-based food components on cardiovascular and metabolic risk factors at 1, 2, and 5 years of corrected age. Primary outcomes include assessments of fasting blood glucose levels, blood pressure levels, and the distensibility of the descending aorta using validated echocardiographic protocols at 5 years of corrected age. The test group, which consists of 200 preterm infants, will therefore be compared to a control group of 100 term-born infants and a historical control group recruited previously.

Discussion

Given the emerging implications of an increased cardiovascular risk profile in the potentially growing population of preterm infants, further research on the mitigation of long-term morbidities in formerly preterm infants is urgently warranted. Further optimizing preterm infants’ nutrition by removing bovine-milk-based food components may therefore be an interesting approach worth pursuing.

Trial registration

ClinicalTrials.govNCT04413994. Registered on 4 June 2020.
REBOARREST, resuscitative endovascular balloon occlusion of the aorta in non-traumatic out-of-hospital cardiac arrest: a study protocol for a randomised, parallel group, clinical multicentre trial
Authors: Brede Jostein Rødseth , Skulberg Arne Kristian , Rehn Marius , Thorsen Kjetil , Klepstad Pål , Tylleskär Ida , Farbu Bjørn , Dale Jostein , Nordseth Trond , Wiseth Rune , Krüger Andreas Jørstad
Published: July 2021

Background

Survival after out-of-hospital cardiac arrest (OHCA) is poor and dependent on high-quality cardiopulmonary resuscitation. Resuscitative endovascular balloon occlusion of the aorta (REBOA) may be advantageous in non-traumatic OHCA due to the potential benefit of redistributing the cardiac output to organs proximal to the aortic occlusion. This theory is supported by data from both preclinical studies and human case reports.

Methods

This multicentre trial will enrol 200 adult patients, who will be randomised in a 1:1 ratio to either a control group that receives advanced cardiovascular life support (ACLS) or an intervention group that receives ACLS and REBOA. The primary endpoint will be the proportion of patients who achieve return of spontaneous circulation with a duration of at least 20 min. The secondary objectives of this trial are to measure the proportion of patients surviving to 30 days with good neurological status, to describe the haemodynamic physiology of aortic occlusion during ACLS, and to document adverse events.

Discussion

Results from this study will assess the efficacy and safety of REBOA as an adjunctive treatment for non-traumatic OHCA. This novel use of REBOA may contribute to improve treatment for this patient cohort.

Trial registration

The trial is approved by the Regional Committee for Medical and Health Research Ethics in Norway (reference 152504) and is registered at ClinicalTrials.gov (reference NCT04596514) and as Universal Trial Number WHO: U1111-1253-0322.
SUMOylated non-canonical polycomb PRC1.6 complex as a prerequisite for recruitment of transcription factor RBPJ
Authors: Sotomska Małgorzata , Liefke Robert , Ferrante Francesca , Schwederski Heiko , Oswald Franz , Borggrefe Tilman
Published: July 2021

Background

Notch signaling controls cell fate decisions in many contexts during development and adult stem cell homeostasis and, when dysregulated, leads to carcinogenesis. The central transcription factor RBPJ assembles the Notch coactivator complex in the presence of Notch signaling, and represses Notch target gene expression in its absence.

Results

We identified L3MBTL2 and additional members of the non-canonical polycomb repressive PRC1.6 complex in DNA-bound RBPJ associated complexes and demonstrate that L3MBTL2 directly interacts with RBPJ. Depletion of RBPJ does not affect occupancy of PRC1.6 components at Notch target genes. Conversely, absence of L3MBTL2 reduces RBPJ occupancy at enhancers of Notch target genes. Since L3MBTL2 and additional members of the PRC1.6 are known to be SUMOylated, we investigated whether RBPJ uses SUMO-moieties as contact points. Indeed, we found that RBPJ binds to SUMO2/3 and that this interaction depends on a defined SUMO-interaction motif. Furthermore, we show that pharmacological inhibition of SUMOylation reduces RBPJ occupancy at Notch target genes.

Conclusions

We propose that the PRC1.6 complex and its conjugated SUMO-modifications provide a favorable environment for binding of RBPJ to Notch target genes.
Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia
Authors: Barliana Melisa Intan , Kusuma Arif Satria Wira , Insani Widya Norma , Alfian Sofa Dewi , Diantini Ajeng , Mutakin Mutakin , Rostinawati Tina , Herlambang Herlambang , Puspitasari Irma Melyani , Suwantika Auliya Abdurrohim , Abdulah Rizky
Published: July 2021

Objective

The risk of contracting tuberculosis (TB) and the efficacy of TB therapy are affected by several factors, including genetic variation among populations. In the Indonesian population, data on the genes involved in drug transport and metabolism of TB therapy are limited. The aim of this study was to identify the genetic profile of the ABCB1 gene (rs1128503 and rs1045642) and CYP2E1 gene (rs3813867) in Indonesians with TB. This study was a cross-sectional study of 50 TB outpatients in Jambi city, Indonesia. Sociodemographic characteristics were obtained from medical records. Whole blood was collected, and genomic DNA was isolated. Single nucleotide polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism with HaeIII, MboI, and PstI for rs1128503, rs1045642 (ABCB1), and rs3813867 (CYP2E1), respectively.

Result

The frequency of alleles of each gene was analyzed by Hardy–Weinberg equilibrium. The genetic profiles of ABCB1 rs1128503 and rs1045642 were varied (CC, CT, TT), while CYP2E1 rs3813867 was present in CC (wild type). The genetic variations of ABCB1 and CYP2E1 may have no significant correlation with the duration of TB therapy. Nevertheless, this study may provide as preliminary results for the genetic profiles of ABCB1 (rs1128503, rs1045642) and CYP2E1 (rs3813867) in the Indonesia population.
Chromatin insulation dynamics in glioblastoma: challenges and future perspectives of precision oncology
Authors: Sesé Borja , Ensenyat-Mendez Miquel , Iñiguez Sandra , Llinàs-Arias Pere , Marzese Diego M.
Published: July 2021

Glioblastoma (GBM) is the most aggressive primary brain tumor, having a poor prognosis and a median overall survival of less than two years. Over the last decade, numerous findings regarding the distinct molecular and genetic profiles of GBM have led to the emergence of several therapeutic approaches. Unfortunately, none of them has proven to be effective against GBM progression and recurrence. Epigenetic mechanisms underlying GBM tumor biology, including histone modifications, DNA methylation, and chromatin architecture, have become an attractive target for novel drug discovery strategies. Alterations on chromatin insulator elements (IEs) might lead to aberrant chromatin remodeling via DNA loop formation, causing oncogene reactivation in several types of cancer, including GBM. Importantly, it is shown that mutations affecting the isocitrate dehydrogenase (IDH) 1 and 2 genes, one of the most frequent genetic alterations in gliomas, lead to genome-wide DNA hypermethylation and the consequent IE dysfunction. The relevance of IEs has also been observed in a small population of cancer stem cells known as glioma stem cells (GSCs), which are thought to participate in GBM tumor initiation and drug resistance. Recent studies revealed that epigenomic alterations, specifically chromatin insulation and DNA loop formation, play a crucial role in establishing and maintaining the GSC transcriptional program. This review focuses on the relevance of IEs in GBM biology and their implementation as a potential theranostic target to stratify GBM patients and develop novel therapeutic approaches. We will also discuss the state-of-the-art emerging technologies using big data analysis and how they will settle the bases on future diagnosis and treatment strategies in GBM patients.
Genome analysis of Salmonella strains isolated from imported frozen fish in Burkina Faso
Authors: Kagambèga Assèta , Belem Salifou , McMillan Elizabeth A. , Hiott Lari M. , Ramadan Hazem , Soro Daniel K. , Sharma Poonam , Gupta Sushim K. , Barro Nicolas , Jackson Charlene R. , Frye Jonathan G.
Published: July 2021

Purpose

Fish is an excellent source of protein and vitamins for humans, but improperly handled, fish can expose consumers to pathogenic bacteria. This study was aimed to isolate and characterize the genomes of Salmonella strains isolated from imported fish sold in the open market in Ouagadougou.

Methods

One hundred and fifty-nine fish were collected from open markets and were cultured for Salmonella. Antimicrobial susceptibility was determined by broth microdilution. Whole-genome sequencing was done to further study antibiotic resistance genes, plasmid replicons, and MSLT types. Serotyping was done using SeqSero 2.

Result

Out of the 159 fish samples analyzed, 30 (18.9%) were found to be contaminated with Salmonella. Among the isolated Salmonella strains, six different serotypes, Nima, Liverpool, Kokomlemle, Teshie, Derby, and Tennessee, were found using SeqSero2. Salmonella Tennessee was the predominant serotype. All the isolates possessed at least one resistance gene. The aac6-Iaa aminoglycoside resistance gene was the most prevalent gene found in the strains. The gene fosA7 was detected in three strains. All the S. Nima isolates were of Multilocus Sequence Type (MLST) 8086, S. Teshie isolate was ST 530; Liverpool was ST 1959; Derby was ST 7880; Kokomlemle was ST 2696. The Tennessee isolates gave two different STs including ST 8395 and 8398.

Conclusion

The presented results highlight the prevalence of Salmonella on imported fish purchased from the open markets. More attention should be paid regarding fish selling conditions in the country to prevent the potential health risk for consumers.
Brain organoid: a 3D technology for investigating cellular composition and interactions in human neurological development and disease models in vitro
Authors: Agboola Oluwafemi Solomon , Hu Xinglin , Shan Zhiyan , Wu Yanshuang , Lei Lei
Published: July 2021

The study of human brain physiology, including cellular interactions in normal and disease conditions, has been a challenge due to its complexity and unavailability. Induced pluripotent stem cell (iPSC) study is indispensable in the study of the pathophysiology of neurological disorders. Nevertheless, monolayer systems lack the cytoarchitecture necessary for cellular interactions and neurological disease modeling. Brain organoids generated from human pluripotent stem cells supply an ideal environment to model both cellular interactions and pathophysiology of the human brain. This review article discusses the composition and interactions among neural lineage and non-central nervous system cell types in brain organoids, current studies, and future perspectives in brain organoid research. Ultimately, the promise of brain organoids is to unveil previously inaccessible features of neurobiology that emerge from complex cellular interactions and to improve our mechanistic understanding of neural development and diseases.

Graphical abstract
MLSolvA: solvation free energy prediction from pairwise atomistic interactions by machine learning
Authors: Lim Hyuntae , Jung YounJoon
Published: July 2021

Recent advances in machine learning technologies and their applications have led to the development of diverse structure–property relationship models for crucial chemical properties. The solvation free energy is one of them. Here, we introduce a novel ML-based solvation model, which calculates the solvation energy from pairwise atomistic interactions. The novelty of the proposed model consists of a simple architecture: two encoding functions extract atomic feature vectors from the given chemical structure, while the inner product between the two atomistic feature vectors calculates their interactions. The results of 6239 experimental measurements achieve outstanding performance and transferability for enlarging training data owing to its solvent-non-specific nature. An analysis of the interaction map shows that our model has significant potential for producing group contributions on the solvation energy, which indicates that the model provides not only predictions of target properties but also more detailed physicochemical insights.