bluuebunny/crossref_metadata_2025 huggingface dataset:
A training program for obstetrics point-of-care ultrasound to 514 rural healthcare providers in Kenya
Authors: Wachira James , Matheka Duncan Mwangangi , Masheti Sheila Ayesa , Githemo Grace Kirigo , Shah Sachita , Haldeman Matthew S. , Ramos Mena , Bergman Kevin
Published: December 2023

Background

Ultrasound is a crucial and effective diagnostic tool in medicine. Recent advancements in technology have led to increased use of point-of-care ultrasound (POCUS). Access to ultrasound equipment and training programs in low-and middle-income countries (LMICs) is limited. Despite the World Health Organization (WHO) recommendations for universal antenatal ultrasounds, POCUS for reproductive health applications has not been widely used in LMICs. We describe here the feasibility of implementation of a training of obstetrics point-of-care ultrasound (OB POCUS) for high-risk conditions in rural public healthcare facilities in Kenya with partnership from Butterfly Network, Global Ultrasound Institute, and Kenyatta University.

Methods

As part of the initiation of a large-scale implementation study of OB POCUS, clinician trainees were recruited from rural Kenyan hospitals for participation in a series of five-day POCUS workshops held between September and December 2022. Trainers provided brief didactic lessons followed by hands-on training with live models and at regional clinical sites for 5 OB POCUS applications. Instructor-observed assessment of students’ scanning and image interpretation occurred over the training period. Assessment of knowledge and confidence was performed via an online pre-test and post-test as well as Objective Structured Clinical Examination (OSCE) was administered at course completion.

Results

Five hundred and fourteen mid-level Health Care Providers (HCPs) in Kenya were trained over a three-month period through in-person didactic sessions, bedside instruction, and clinical practice over a 5-day period with a trainer: trainee ratio of approximately 1:5. Out of the 514 trained HCPs, 468 were from 8 rural counties with poor maternal and neonatal outcomes, while the remaining 46 were from nearby facilities. OB POCUS topics covered included: malpresentation, multiple gestation, fetal cardiac activity, abnormalities of the placenta and amniotic fluid volume. There was marked improvement in the post training test scores compared to the pretest scores.

Conclusion

Our implementation description serves as a guide for successful rapid dissemination of OB POCUS training for mid-level providers. Our experience demonstrates the feasibility of a short intensive POCUS training to rapidly establish specific POCUS skills in efforts to rapidly scale POCUS access and services. There is a widespread need for expanding access to ultrasound in pregnancy through accessible OB POCUS training programs. An implementation study is currently underway to assess the patient and systems-level impact of the training.
Better together: utilizing an interprofessional course and escape room to educate healthcare students about opioid use disorder
Authors: Schmuhl Kelsey K. , Nagel Steven , Tamburro Ross , Jewell T’Bony M. , Gilbert Emily , Gonzalez Anthony , Sullivan Donald L. , Sprague Jon E.
Published: December 2023

Background

The aim of the present study was to determine the impact of an innovative interprofessional educational activity on healthcare professional students’ learning. The educational activity targeted student knowledge of opioid use disorder (OUD) and perceptions of working with an interprofessional team while caring for patients with OUD.

Methods

Students from nursing, pharmacy, physician assistant, dentistry, social work, and medicine programs were recruited to participate in the interprofessional educational activity. The educational experience included seven asynchronous modules and a virtual synchronous escape room. Prior to the educational programming, participants completed a pre-survey that assessed their knowledge and attitudes towards working on an interprofessional team and perceptions of patients with OUD. The asynchronous modules were required in order to participate in the escape room and each module contained its own pre/post quiz to assess student knowledge.

Results

A total of 402 students participated in the course. Prior to participating in the course, students disagreed that they had extensive educational experience with SUD (2.45 ± 0.79). The students displayed significant improvement in the knowledge based areas after completing the seven asynchronous modules. The largest significant area of knowledge-based improvement was seen in treatment of OUD where on the pre-quiz 65.54 ± 20.21% were answered correctly compared to 95.97 ± 9.61% on the post-quiz. Participation in the escape room significantly changed the students’ perceptions of working in interprofessional teams while managing patients with OUD. Of the eleven perception variables assessed, seven showed a significant increase in the post-survey. Following the escape room, participants also strongly agreed that they now would refer patients to colleagues in other disciplines.

Conclusions

An interprofessional educational experience including both an asynchronous course and virtual synchronous escape room can increase participant knowledge around OUD and may improve student perceptions of working with an interprofessional team and caring for patients with OUD.
Preparing for success in final summative medical specialist examinations: The case for RACE
Authors: Allen Penelope , Jessup Belinda , Kirschbaum Melissa , Khanal Santosh , Baker-Smith Victoria , Graham Barnabas , Barnett Tony
Published: December 2023

Background

Failure rates on medical specialist final summative examinations in Australia are high, regardless of speciality. Examination failure can have detrimental psycho-social, financial and job security effects on the trainee, while delays in completion of training adversely impacts workforce growth and health outcomes for the community. The study aimed to explore the preparation factors that contribute to ophthalmology trainee success in their final summative examination.

Methods

Semi-structured in-depth interviews were conducted with 29 participants via telephone or Zoom with ophthalmology trainees and Fellows. To be eligible, interviewees had to have sat the Royal Australian and New Zealand College of Ophthalmologists Advanced Clinical Examination (RACE) within the past five years or were providing supervision to trainees preparing for RACE. Interviews were audio-recorded, transcribed and thematically analysed.

Results

Examination success was underpinned by six themes relating to preparation: (i) ‘Those who fail to plan, plan to fail’, which related to development and adherence to a study plan; (ii) ‘It takes a village’ encompassed trainees establishing and activating personal and professional supports; (iii) ‘Get to know your opponent’, which encompassed developing an understanding of the examination construct, format and requirements; (iv) ‘There is no substitute for hard work’, which related to intensive study over a period of 12–18 months; (v) ‘Keep pace with the herd’, which referred to benchmarking preparation efforts and progress against peers; and (vi) ‘Don’t jump the gun’, which related to ensuring readiness to sit.

Conclusions

Maximising medical specialist examination pass rates is in the best interest of trainees, training Colleges, health care systems and communities. Recognising and facilitating preparation approaches that foster success in final summative examinations are the collective responsibility of trainees, specialist training Colleges, training networks and health systems. Trainees need to plan for examination success, be self-determined to commit to intensive study over an extended time period and be realistic about their readiness to sit.
Ethical considerations for biobanking and use of genomics data in Africa: a narrative review
Authors: Amoakoh-Coleman Mary , Vieira Dorice , Abugri James
Published: December 2023

Background

Biobanking and genomic research requires collection and storage of human tissue from study participants. From participants’ perspectives within the African context, this can be associated with fears and misgivings due to a myriad of factors including myths and mistrust of researchers. From the researchers angle ethical dilemmas may arise especially with consenting and sample reuse during storage. The aim of this paper was to explore these ethical considerations in the establishment and conduct of biobanking and genomic studies in Africa.

Methods

We conducted a narrative synthesis following a comprehensive search of nine (9) databases and grey literature. All primary research study designs were eligible for inclusion as well as both quantitative and qualitative evidence from peer reviewed journals, spanning a maximum of 20 years (2000–2020). It focused on research work conducted in Africa, even if data was stored or analysed outside the region.

Results

Of 2,663 title and abstracts screened, 94 full texts were retrieved and reviewed for eligibility. We included 12 studies (7 qualitative; 4 quantitative and one mixed methods).

Ethical issues described in these papers related to community knowledge and understanding of biobanking and genomic research, regulation, and governance of same by research ethics committees, enrolment of participants, types of informed consents, data collection, storage, usage and sharing as well as material transfer, returning results and benefit sharing. ca. Biospecimen collection and storage is given in trust and participants expect confidentially of data and results generated. Most participants are comfortable with broad consent due to trust in researchers, though a few would like to be contacted for reconsenting in future studies, and this would depend on whether the new research is for good cause. Sharing data with external partners is welcome in some contexts but some research participants did not trust foreign researchers.

Conclusion

Biobanking and genomic studies are a real need in Africa. Linked to this are ethical considerations related to setting up and participation in biobanks as well as data storage, export, use and sharing. There is emerging or pre-existing consensus around the acceptability of broad consent as a suitable model of consent, the need for Africans to take the lead in international collaborative studies, with deliberate efforts to build capacity in local storage and analysis of samples and employ processes of sample collection and use that build trust of communities and potential study participants. Research ethics committees, researchers and communities need to work together to work together to adapt and use clearly defined ethical frameworks, guidelines, and policy documents to harmonize the establishment and running of biobanking and genomic research in Africa.
Ibrutinib versus bendamustine plus rituximab for first-line treatment of 65 or older patients with untreated chronic lymphocytic leukemia without del(17p)/TP53 mutation in China: a lifetime economic research study
Authors: Hong Yuan , Chen Xichuang , Hong Yuanquan , Xiao Xingfang , Wang Yan , You Xiaohong , Mi Jingyi , Zhou Tao , Zheng Panpan , Huang Zhihu
Published: December 2023

Background

The incidence and mortality rates of patients with chronic lymphocytic leukemia (CLL) in China have recently increased. This study performed a long-term economic evaluation of the first-line treatment strategies ibrutinib (IB) or bendamustine (BE) plus rituximab (RI) for previously untreated older patients with CLL without the del(17p)/TP53 mutation in China.

Methods

Based on clinical data from large, randomized trials, a Markov model including four disease states (event-free survival, treatment failure, post-treatment failure, and death) was used to estimate the incremental costs per quality adjusted-life year (QALY) gained from the first-line IB strategy versus the BE plus RI strategy over a 10-year period. All costs were adjusted to 2022 values based on the Chinese Consumer Price Index, and all costs and health outcomes were discounted at an annual rate of 5%. Sensitivity analysis was performed to confirm the robustness of base-case results.

Results

Compared to the first-line BE plus RI strategy, first-line IB treatment achieved 1.17 additional QALYs, but was accompanied by $88,046.78 (estimated in 2022 US dollars) in decremental costs per patient over 10 years. Thus, first-line treatment with IB appeared to have absolute dominance compared to the BE plus RI strategy. Sensitivity analysis confirmed the robustness of these results.

Conclusions

The first-line treatment with IB is absolutely cost-effective compared to the first-line BE plus RI treatment strategy for 65 or older patients with CLL without the del (17p)/TP53 mutation from the Chinese payer perspective. Therefore, it is strongly recommended that Chinese health authorities select the former strategy for these CLL patients.
Diversity across organisational scale emerges through dispersal ability and speciation dynamics in tropical fish
Authors: Keggin Thomas , Waldock Conor , Skeels Alexander , Hagen Oskar , Albouy Camille , Manel Stéphanie , Pellissier Loïc
Published: December 2023

Background

Biodiversity exists at different levels of organisation: e.g. genetic, individual, population, species, and community. These levels of organisation all exist within the same system, with diversity patterns emerging across organisational scales through several key processes. Despite this inherent interconnectivity, observational studies reveal that diversity patterns across levels are not consistent and the underlying mechanisms for variable continuity in diversity across levels remain elusive. To investigate these mechanisms, we apply a spatially explicit simulation model to simulate the global diversification of tropical reef fishes at both the population and species levels through emergent population-level processes.

Results

We find significant relationships between the population and species levels of diversity which vary depending on both the measure of diversity and the spatial partitioning considered. In turn, these population-species relationships are driven by modelled biological trait parameters, especially the divergence threshold at which populations speciate.

Conclusions

To explain variation in multi-level diversity patterns, we propose a simple, yet novel, population-to-species diversity partitioning mechanism through speciation which disrupts continuous diversity patterns across organisational levels. We expect that in real-world systems this mechanism is driven by the molecular dynamics that determine genetic incompatibility, and therefore reproductive isolation between individuals. We put forward a framework in which the mechanisms underlying patterns of diversity across organisational levels are universal, and through this show how variable patterns of diversity can emerge through organisational scale.
Minimal important difference of the 12-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 in persons with chronic low back pain
Authors: Wong Jessica J. , Hogg-Johnson Sheilah , De Groote Wouter , Ćwirlej-Sozańska Agnieszka , Garin Olatz , Ferrer Montse , Acuña Àngels Pont , Côté Pierre
Published: December 2023

Background

The World Health Organization Disability Assessment Schedule 2.0 12-item survey (WHODAS-12) is a questionnaire developed by the WHO to measure functioning across health conditions, cultures, and settings. WHODAS-12 consists of a subset of the 36 items of WHODAS-2.0 36-item questionnaire. Little is known about the minimal important difference (MID) of WHODAS-12 in persons with chronic low back pain (LBP), which would be useful to determine whether rehabilitation improves functioning to an extent that is meaningful for people experiencing the condition. Our objective was to estimate an anchor-based MID for WHODAS-12 questionnaire in persons with chronic LBP.

Methods

We analyzed data from two cohort studies (identified in our previous systematic review) conducted in Europe that measured functioning using the WHODAS-36 in adults with chronic LBP. Eligible participants were adults with chronic LBP with scores on another measure as an anchor to indicate participants with small but important changes in functioning over time [Short-form-36 Physical Functioning (SF36-PF) or Oswestry Disability Index (ODI)] at baseline and follow-up (study 1: 3-months post-treatment; study 2: 1-month post-discharge from hospital). WHODAS-12 scores were constructed as sums of the 12 items (scored 0–4), with possible scores ranging from 0 to 48. We calculated the mean WHODAS-12 score in participants who achieved a small but meaningful improvement on SF36-PF or ODI at follow-up. A meaningful improvement was an MID of 4–16 on ODI or 5–16 on SF36-PF.

Results

Of 70 eligible participants in study 1 (mean age = 54.1 years, SD = 14.7; 69% female), 18 achieved a small meaningful improvement based on SF-36 PF. Corresponding mean WHODAS-12 change score was − 3.22/48 (95% CI -4.79 to -1.64). Of 89 eligible participants in study 2 (mean age = 65.5 years, SD = 11.5; 61% female), 50 achieved a small meaningful improvement based on ODI. Corresponding mean WHODAS-12 change score was − 5.99/48 (95% CI − 7.20 to -4.79).

Conclusions

Using an anchor-based approach, the MID of WHODAS-12 is estimated at -3.22 (95% CI -4.79 to -1.64) or -5.99 (95% CI − 7.20 to -4.79) in adults with chronic LBP. These MID values inform the utility of WHODAS-12 in measuring functioning to determine whether rehabilitation or other health services achieve a minimal difference that is meaningful to patients with chronic LBP.
Experience of traumatic events in people with severe mental illness in a low-income country: a qualitative study
Authors: Ng Lauren C. , Hook Kimberly , Hailemariam Maji , Selamu Medhin , Fekadu Abebaw , Hanlon Charlotte
Published: December 2023

Background

This study describes the trauma experiences of people with severe mental illness (SMI) in Ethiopia and presents a model of how SMI and trauma exposure interact to reduce functioning and quality of life in this setting.

Methods

A total of 53 participants living and working in a rural district in southern Ethiopia were interviewed: 18 people living with SMI, 21 caregivers, and 14 primary health care providers.

Results

Many participants reported that exposure to traumatic and stressful events led to SMI, exacerbated SMI symptoms, and increased caregiver stress and distress. In addition, SMI symptoms and caregiver desperation, stress or stigma were also reported to increase the possibility of trauma exposure.

Conclusions

Results suggest it is incumbent upon health professionals and the broader health community to view trauma exposure (broadly defined) as a public health problem that affects all, particularly individuals with SMI.
Circular RNA circATP9A promotes non-small cell lung cancer progression by interacting with HuR and by promoting extracellular vesicles-mediated macrophage M2 polarization
Authors: Yao Yuanshan , Chen Chunji , Wang Jing , Xuan Haojie , Chen Xiuxiu , Li Zheng , Yang Fuzhi , Wang Bin , Lin Siyun , Li Saitian , Tang Dongfang , Gong Libao , Gao Wen
Published: December 2023

Background

CircRNA is recognized for its significant regulatory function across various cancers. However, its regulatory role in non-small cell lung cancer (NSCLC) is still largely uncharted.

Methods

Analysis based on public databases is completed using R software. circATP9A was identified by two circRNA datasets of NSCLC from the Gene Expression Omnibus database. To examine the impact of circATP9A on the phenotype of NSCLC, we conducted both in vitro and in vivo functional experiments. The mRNA and protein levels of specific molecules were determined through quantitative real-time PCR and western blot assays. RNA pulldown and RNA immunoprecipitation assays were performed to verify the interaction between RNA and protein. The functional role of extracellular vesicles (EVs)-circATP9A on tumor-associated macrophage (TAM) polarization was assessed using co-culture system and cell flow cytometry.

Results

Here, we elucidates the functional role of circATP9A in NSCLC. We demonstrated that circATP9A can foster the progression of NSCLC through in vivo and in vitro experiments. From a mechanistic standpoint, circATP9A can interact with the HuR protein to form an RNA–protein complex, subsequently amplifying the mRNA and protein levels of the target gene NUCKS1. Further, the PI3K/AKT/mTOR signaling was identified as the downstream pathways of circATP9A/HuR/NUCKS1 axis. More notably, hnRNPA2B1 can mediate the incorporation of circATP9A into EVs. Subsequently, these EVs containing circATP9A induce the M2 phenotype of TAMs, thereby facilitating NSCLC development.

Conclusions

Our discoveries indicate that circATP9A could serve as a promising diagnostic indicator and a therapeutic target for NSCLC.
Meiosis in an asymmetric dikaryotic genome of Tremella fuciformis Tr01 facilitates new chromosome formation
Authors: Deng Youjin , Guo Lin , Lin Longji , Li Yuefeng , Zhang Jinxiang , Zhang Yue , Yuan Bin , Ke Lina , Xie Baogui , Ming Ray
Published: December 2023

Background

The dikaryotic stage dominates most of the life cycle in basidiomycetes, and each cell carries two different haploid nuclei. Accurate phasing of these two nuclear genomes and their interactions have long been of interest.

Results

We combine PacBio HiFi reads, Nanopore ultra-long reads, and Hi-C data to generate a complete, high-quality asymmetric dikaryotic genome of Tremella fuciformis Tr01, including Haplotypes A and B genomes. We assemble a meiotic haploid DBZ04 genome and detect three recombination events in these two haplotypes. We identify several chromosomal rearrangements that lead to differences in chromosome number, length, content, and sequence arrangement between these two haplotypes. Each nucleus contains a two-speed genome, harboring three accessory chromosomes and two accessory compartments that affect horizontal chromatin transfer between nuclei. We find few basidiospores are ejected from fruiting bodies of Tr01. Most monospore isolates sequenced belong to Tr01-Haplotype A genome architecture. More than one-third of monospore isolates carry one or two extra chromosomes including Chr12B and two new chromosomes ChrN1 and ChrN2. We hypothesize that homologous regions of seven sister chromatids pair into a large complex during meiosis, followed by inter-chromosomal recombination at physical contact sites and formation of new chromosomes.

Conclusion

We assemble two haplotype genomes of T. fuciformis Tr01 and provide the first overview of basidiomycetous genomes with discrete genomic architecture. Meiotic activities of asymmetric dikaryotic genomes result in formation of new chromosomes, aneuploidy of some daughter cells, and inviability of most other daughter cells. We propose a new approach for breeding of sporeless mushroom.
Clinical and cost-effectiveness of ‘Live Well with Parkinson’s’ self-management intervention versus treatment as usual for improving quality of life for people with Parkinson’s: study protocol for a randomised controlled trial
Authors: Walters Kate , Armstrong Megan , Gardner Benjamin , Ambler Gareth , Hunter Rachael , Maydon Bev , Davies Nathan , Atkinson Catherine , Brown Richard , Rookes Tasmin , Davis Daniel , Schrag Anette
Published: December 2023

Background

The Live Well with Parkinson’s Self-Management Toolkit is designed for use in the NHS to support people with Parkinson’s, their carers and health professionals in managing motor and non-motor symptoms and promoting well-being. The Toolkit was developed based on theory-based behaviour change and self-management techniques in consultation with people living with Parkinson’s and health and social care practitioners. There are digital (e-Toolkit) and paper (manual) versions.

Methods

Single-blind two-arm randomised controlled trial RCT of clinical effectiveness and cost-effectiveness of the Toolkit, facilitated by up to six sessions with a trained non-specialist supporter, in improving quality of life. People with Parkinson’s will be assessed at baseline, 6 and 12 months. Assessors will be blind to the treatment group. The primary outcome measure is the Parkinson’s Disease Questionnaire (PDQ-39, Parkinson’s related quality of life) score at 12 months. Secondary outcome measures include the MDS Unified Parkinson’s Disease Rating Scale (Part I, II, III, IV), EQ-5D, and a Client Service Receipt Inventory shortened, adapted for Parkinson’s. Carer outcomes include the Zarit Carer Burden Inventory and Carer Quality of Life Questionnaire for Parkinsonism. A total of 338 people with Parkinson’s, and their carers if appropriate, will be recruited from diverse settings across England. Those with advanced dementia, at end-of-life or with atypical Parkinsonism will be excluded. A parallel mixed methods process evaluation will explore the factors promoting or inhibiting implementation, uptake, use, effectiveness and cost-effectiveness of the Toolkit and sessions.

Discussion

If successful, the Live Well with Parkinson’s Toolkit could be used as a model for other complex long-term disorders, including dementia. This would bridge existing gaps in the NHS (as shown by the national Parkinson’s audit data), by enabling patients and carers to access personalised information, advice and support on symptom management and ‘living well’ with Parkinson’s.

Trial registration

ISRCTN92831552. Registered on 26th Oct 2021.
A small stretch of poor codon usage at the beginning of dengue virus open reading frame may act as a translational checkpoint
Authors: Yimyaem Maneenop , Jitobaom Kunlakanya , Auewarakul Prasert
Published: December 2023

Objective

Rare codons were previously shown to be enriched at the beginning of the dengue virus (DENV) open reading frame. However, the role of rare codons in regulating translation efficiency and replication of DENV remains unclear. The present study aims to clarify the significance of rare codon usage at the beginning of DENV transcripts using the codon adaptation index (CAI).

Methodology

CAIs of the whole starting regions of DENV transcripts as well as 18-codon sliding windows of the regions were analyzed.

Results

One of the intriguing findings is that those rare codons do not typically result in uniformly low CAI in the starting region with rare codons. However, it shows a notable local drop in CAI around the 50th codon in all dengue serotypes. This suggests that there may be a translational checkpoint at this site and that the rare codon usage upstream to this checkpoint may not be related to translational control.
Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature
Authors: Tsuge Mitsuru , Shigehara Kenji , Uda Kazuhiro , Kawano Seiji , Iwamuro Masaya , Saito Yukie , Yashiro Masato , Ikeda Masanori , Tsukahara Hirokazu
Published: December 2023

Background

Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.

Case presentation

A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.

Conclusions

Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.
Clinicopathological and prognostic value of calcification morphology descriptors in ductal carcinoma in situ of the breast: a systematic review and meta-analysis
Authors: van Leeuwen Merle M. , Doyle Shannon , van den Belt–Dusebout Alexandra W. , van der Mierden Stevie , Loo Claudette E. , Mann Ritse M. , Teuwen Jonas , Wesseling Jelle
Published: December 2023

Background

Calcifications on mammography can be indicative of breast cancer, but the prognostic value of their appearance remains unclear. This systematic review and meta-analysis aimed to evaluate the association between mammographic calcification morphology descriptors (CMDs) and clinicopathological factors.

Methods

A comprehensive literature search in Medline via Ovid, Embase.com, and Web of Science was conducted for articles published between 2000 and January 2022 that assessed the relationship between CMDs and clinicopathological factors, excluding case reports and review articles. The risk of bias and overall quality of evidence were evaluated using the QUIPS tool and GRADE. A random-effects model was used to synthesize the extracted data. This systematic review is reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).

Results

Among the 4715 articles reviewed, 29 met the inclusion criteria, reporting on 17 different clinicopathological factors in relation to CMDs. Heterogeneity between studies was present and the overall risk of bias was high, primarily due to small, inadequately described study populations. Meta-analysis demonstrated significant associations between fine linear calcifications and high-grade DCIS [pooled odds ratio (pOR), 4.92; 95% confidence interval (CI), 2.64–9.17], (comedo)necrosis (pOR, 3.46; 95% CI, 1.29–9.30), (micro)invasion (pOR, 1.53; 95% CI, 1.03–2.27), and a negative association with estrogen receptor positivity (pOR, 0.33; 95% CI, 0.12–0.89).

Conclusions

CMDs detected on mammography have prognostic value, but there is a high level of bias and variability between current studies. In order for CMDs to achieve clinical utility, standardization in reporting of CMDs is necessary.

Critical relevance statement

Mammographic calcification morphology descriptors (CMDs) have prognostic value, but in order for CMDs to achieve clinical utility, standardization in reporting of CMDs is necessary.

Systematic review registration

CRD42022341599

Key points

• Mammographic calcifications can be indicative of breast cancer.

• The prognostic value of mammographic calcifications is still unclear.

• Specific mammographic calcification morphologies are related to lesion aggressiveness.

• Variability between studies necessitates standardization in calcification evaluation to achieve clinical utility.

Graphical Abstract
Emerging role of mesenchymal stromal cells in gynecologic cancer therapy
Authors: Song Yizuo , Liu Hejing , Pan Shuya , Xiang Xinli , Ye Miaomiao , Zhu Xueqiong
Published: December 2023

Mesenchymal stromal cells (MSCs) show considerable promise in regenerative medicine with superior anti-fibrotic, immunomodulatory, and angiogenic functions. More recently, discovered with the tumor tropism, MSCs have been exploited as the basis of targeted cancer therapy. In this scenario, MSCs can directly home to tumor tissues and play anti-tumor properties. In addition, MSCs, MSC-derived exosomes and MSC-derived membranes are often developed as carriers for precisely delivering cytotoxic agents to cancer sites, including chemotherapeutic drugs, therapeutic genes, or oncolytic viruses. However, it has revealed the tumorigenic risk of MSCs as an important component within the tumor microenvironment, hampering the translation of MSC-based cancer therapies into clinical settings. Therefore, in this review, we introduce the specific tumor-tropic ability of MSCs and underlying mechanisms. We also summarize the current application of MSC-based therapeutic approaches in treating gynecologic cancers, mainly including cervical, ovarian, and endometrial cancers. Moreover, we discuss the main challenges that the current MSC-based cancer therapies are facing.
Gene editing and cardiac disease modelling for the interpretation of genetic variants of uncertain significance in congenital heart disease
Authors: Fear Vanessa S. , Forbes Catherine A. , Shaw Nicole C. , Farley Kathryn O. , Mantegna Jessica L. , Htun Jasmin P. , Syn Genevieve , Viola Helena , Cserne Szappanos Henrietta , Hool Livia , Ward Michelle , Baynam Gareth , Lassmann Timo
Published: December 2023

Background

Genomic sequencing in congenital heart disease (CHD) patients often discovers novel genetic variants, which are classified as variants of uncertain significance (VUS). Functional analysis of each VUS is required in specialised laboratories, to determine whether the VUS is disease causative or not, leading to lengthy diagnostic delays. We investigated stem cell cardiac disease modelling and transcriptomics for the purpose of genetic variant classification using a GATA4 (p.Arg283Cys) VUS in a patient with CHD.

Methods

We performed high efficiency CRISPR gene editing with homology directed repair in induced pluripotent stem cells (iPSCs), followed by rapid clonal selection with amplicon sequencing. Genetic variant and healthy matched control cells were compared using cardiomyocyte disease modelling and transcriptomics.

Results

Genetic variant and healthy cardiomyocytes similarly expressed Troponin T (cTNNT), and GATA4. Transcriptomics analysis of cardiomyocyte differentiation identified changes consistent with the patient’s clinical human phenotype ontology terms. Further, transcriptomics revealed changes in calcium signalling, and cardiomyocyte adrenergic signalling in the variant cells. Functional testing demonstrated, altered action potentials in GATA4 genetic variant cardiomyocytes were consistent with patient cardiac abnormalities.

Conclusions

This work provides in vivo functional studies supportive of a damaging effect on the gene or gene product. Furthermore, we demonstrate the utility of iPSCs, CRISPR gene editing and cardiac disease modelling for genetic variant interpretation. The method can readily be applied to other genetic variants in GATA4 or other genes in cardiac disease, providing a centralised assessment pathway for patient genetic variant interpretation.
Association between body mass index and myopia in the United States population in the National Health and Nutrition Examination Surveys 1999 to 2008: a cross-sectional study
Authors: Qu Yaohui , Huang Huamin , Zhang Hongxing
Published: December 2023

Background

This study investigated the association between body mass index (BMI) and myopia in the United States.

Methods

This cross-sectional study included 8,000 participants from the 1999 to 2008 National Health and Nutrition Examination Survey (NHANES). BMI was classified into four groups: < 18.5, 18.5 – 24.9, 25–29.9, and > 29.9. Three diagnostic thresholds were used for myopia A\B\C: spherical equivalent ≤ −0.5\−0.75\−1 diopters in the right eye. Multivariate logistic regression analysis and smooth curve fitting were performed to evaluate the association between BMI and myopia.

Results

The incidence of myopia was 39.4%. BMI was correlated with myopia, with each 1 kg/m2 increase in BMI associated with a 1% increase in the risk of myopia (OR, 1.01; 95% CI 1.01 1.02; p < 0.05). In myopia B, after adjusting for confounding factors, compared with the reference group (BMI 18.5–24.9), participants with a BMI of 25–29.9 and greater than 29.9 had a 14% and 25% increased risk of myopia, respectively (OR 1.14; 95% CI 1.01 1.29; p = 0.037, OR 1.25; 95% CI 1.08 1.44; p = 0.003), which was similar to the results for myopic A (OR, 1.15; 95% CI 1.02 1.3; p = 0.027, OR 1.19; 95% CI 1.03 1.37; p = 0.018) and myopia C (OR 1.15; 95% CI 1.01 1.31; p = 0.035, OR 1.18; 95% CI 1.01 1.37; p = 0.032). Moreover, there was a linear relationship between myopia and BMI (p for nonlinearity = 0.767).

Conclusions

Myopia using all three diagnostic thresholds was positively associated with higher BMI. This suggests a potential association between myopia and higher BMI in the American population, warranting further investigations.
Role of the CASZ1 transcription factor in tissue development and disease
Authors: Liu Tiantian , Li Tao , Ke Shaorui
Published: December 2023

The zinc finger transcription factor gene, CASZ1/Castor (Castor zinc finger 1), initially identified in Drosophila, plays a critical role in neural, cardiac, and cardiovascular development, exerting a complex, multifaceted influence on cell fate and tissue morphogenesis. During neurogenesis, CASZ1 exhibits dynamic expression from early embryonic development to the perinatal period, constituting a key regulator in this process. Additionally, CASZ1 controls the transition between neurogenesis and gliomagenesis. During human cardiovascular system development, CASZ1 is essential for cardiomyocyte differentiation, cardiac morphogenesis, and vascular morphology homeostasis and formation. The deletion or inactivation of CASZ1 mutations can lead to human developmental diseases or tumors, including congenital heart disease, cardiovascular disease, and neuroblastoma. CASZ1 can be used as a biomarker for disease prevention and diagnosis as well as a prognostic indicator for cancer. This review explores the unique functions of CASZ1 in tissue morphogenesis and associated diseases, offering new insights for elucidating the molecular mechanisms underlying diseases and identifying potential therapeutic targets for disease prevention and treatment.
The economic fitness of nations in value added. 2000–2014
Authors: Cervantes-Martínez Rosario , Villaseñor–Becerra Jorge
Published: December 2023

In this paper, we explore the Economic Fitness (EF) indicator from the World Bank Database that measures the nations level of international competitiveness. At the same time, using input–output tables, we present our estimations of this new metric, replacing the revealed comparative advantages (RCA) from exports in gross value with an estimate of RCA from exports in domestic value-added (DVA). We find that between 1995 and 2015, there is a positive relationship between Economic Fitness and per capita GDP for low and middle-income countries. Besides, we also show that the estimations of the EF using the domestic value-added content of exports changed significantly from 2000 to 2014 since there has been a widening gap between global exports in gross value and exports in value-added. The latter suggests that, given the increasing levels of productive links at the international level, the competitiveness of nations is also conditioned by how they participate in global production networks.
Umbilical cord blood and cord tissue banking as somatic stem cell resources to support medical cell modalities
Authors: Nagamura-Inoue Tokiko , Nagamura Fumitaka
Published: December 2023

Human umbilical cord blood (CB) and umbilical cord tissue (UC) are attractive sources of somatic stem cells for gene and cell therapies. CB and UC can be obtained noninvasively from donors. CB, a known source of hematopoietic stem cells for transplantation, has attracted attention as a new source of immune cells, including universal chimeric antigen receptor-T cell therapy (CAR-T) and, more recently, universal CAR-natural killer cells. UC-derived mesenchymal stromal cells (UC-MSCs) have a higher proliferation potency than those derived from adult tissues and can be used anon-HLA restrictively. UC-MSCs meet the MSC criteria outlined by the International Society of Gene and Cellular Therapy. UC-MSCs are negative for HLA-DR, CD80, and CD86 and have an immunosuppressive ability that mitigates the proliferation of activated lymphocytes through secreting indoleamine 2,3-dioxygenase 1 and prostaglandin E2, and the expression of PD-L2 and PD-L1. We established the off-the-shelf cord blood/cord bank IMSUT CORD to support novel cell therapy modalities, including the CB-derived immune cells, MSCs, MSCs-derived extracellular vesicles, biological carriers loaded with chemotherapy drugs, prodrug, oncolytic viruses, nanoparticles, human artificial chromosome, combinational products with a scaffold, bio3D printing, and so on.
Evaluation of MR-safe bioptomes for MR-guided endomyocardial biopsy in minipigs: a potential radiation-free clinical approach
Authors: Svetlove Angelika , Ritter Christian O. , Dullin Christian , Schmid Michael , Schauer Senta , Uihlein Johannes , Uecker Martin , Mietsch Matthias , Stadelmann Christine , Lotz Joachim , Unterberg-Buchwald Christina
Published: December 2023

Background

Diagnostic accuracy of endomyocardial biopsy could improve if clinically safe magnetic resonance (MR)-compatible bioptomes were available. We explored two novel MR-compatible cardiac bioptomes for performance, safety, and clinical viability, employing in vivo minipig trials and phase-contrast synchrotron radiation computed microtomography (SRµCT).

Methods

Analysis of ex vivo obtained pig endomyocardial biopsies was performed using phase-contrast SRµCT and conventional two-dimensional histology. The technical performance was evaluated by measuring volume, inner and outer integrities, compression, and histological diagnostic value in 3 sets (6 per set) of biopsies for each experimental bioptome. The bioptomes were tested in vivo in 3 healthy minipigs per bioptome. The clinical feasibility was evaluated by procedural and cutting success as well as histological diagnostic value.

Results

The bioptome with the ‘grind-grind’ design achieved similar values to control in compression (p = 0.822), inner (p = 0.628), and outer (p = 0.507), integrities ex vivo. It showed a better performance in the in vivo real-time MRI setting demonstrating a higher cutting success (91.7%) than the ‘grind-anvil’ (86.2%) design. In both ex vivo and in vivo evaluations, the ‘grind-grind’ design displayed sufficient diagnostic value (83% and 95%). The ‘grind-anvil’ design showed adequate diagnostic value both ex vivo and in vivo (78% and 87.5%) but was not comparable to control according to the three-dimensional (3D) analysis.

Conclusion

A novel MR-compatible bioptome was identified as plausible in a clinical setting. Additionally, SRµCT and subsequent 3D structural analysis could be valuable in the label-free investigation of myocardial tissue at a micrometer level.

Relevance statement

Implementation of MR-guided biopsy can improve animal studies on structural myocardial changes at any point in an experimental setup. With further improvements in guiding catheters, MR-guided biopsy, using the new bioptome, has a potential to increase quality and diagnostic accuracy in patients both with structural and inflammatory cardiomyopathies.

Key points

• Novel MR-compatible bioptomes show promise for a clinical application.

• SRµCT enabled detailed analysis of endomyocardial biopsies.

• The bioptomes showed adequate in vivo performance without major complications.

Graphical Abstract
Interactive Association Between Gut Microbiota and Thyroid Cancer
Authors: Hou Tianzhichao , Wang Qi , Dai Huajie , Hou Yanan , Zheng Jie , Wang Tiange , Lin Hong , Wang Shuangyuan , Li Mian , Zhao Zhiyun , Chen Yuhong , Xu Yu , Lu Jieli , Liu Ruixin , Ning Guang , Wang Weiqing , Xu Min , Bi Yufang
Published: December 2023

Context

The association between the gut microbiota and thyroid cancer remains controversial.

Objective

We aimed to systematically investigate the interactive causal relationships between the abundance and metabolism pathways of gut microbiota and thyroid cancer.

Methods

We leveraged genome-wide association studies for the abundance of 211 microbiota taxa from the MiBioGen study (N = 18 340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N = 7738), and thyroid cancer from the Global Biobank Meta-analysis Initiative (N cases = 6699 and N participants = 1 620 354). We performed a bidirectional Mendelian randomization (MR) to investigate the causality from microbiota taxa and metabolism pathways to thyroid cancer and vice versa. We performed a systematic review of previous observational studies and compared MR results with observational findings.

Results

Eight taxa and 12 metabolism pathways had causal effects on thyroid cancer, where RuminococcaceaeUCG004 genus (P = .001), Streptococcaceae family (P = .016), Olsenella genus (P = .029), ketogluconate metabolism pathway (P = .003), pentose phosphate pathway (P = .016), and L-arginine degradation II in the AST pathway (P = .0007) were supported by sensitivity analyses. Conversely, thyroid cancer had causal effects on 3 taxa and 2 metabolism pathways, where the Holdemanella genus (P = .015) was supported by sensitivity analyses. The Proteobacteria phylum, Streptococcaceae family, Ruminococcus2 genus, and Holdemanella genus were significantly associated with thyroid cancer in both the systematic review and MR, whereas the other 121 significant taxa in observational results were not supported by MR.

Discussions

These findings implicated the potential role of host-microbiota crosstalk in thyroid cancer, while the discrepancy among observational studies calls for further investigations.