bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences of living with idiopathic pulmonary fibrosis in relation to physical activity - “How the hills became steeper and steeper”: a qualitative interview study
Authors: Jernås Anna , Fagevik Olsén Monika , Holmqvist Emma , Danielsbacka Jenny
Published: May 2024

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive disease presenting with symptoms like dyspnoea, dry cough, and fatigue, which affect physical function and quality of life. No earlier qualitative studies have investigated physical activity in IPF. This study aims to explore experiences of living with IPF in relation to physical activity.

Materials and methods

Qualitative interviews were conducted with 14 participants living with IPF. The participants were 77 years old (range: 56–86) and diagnosed with IPF between 2 and 9 years ago. The analysis was performed by qualitative content analysis according to Graneheim and Lundman.

Results

The results indicated that life and one’s ability to be physically active is affected by IPF. Despite this, it seems possible to navigate past obstacles, which was illustrated by an overall theme: “My life is constrained, but I am hanging on”. Two major categories cover topics of IPF being a life changing diagnosis with changes in self-image and changed future plans regarding physical activity, as well as life. Physical activity was perceived to be challenging, yet in many ways used as a strategy, developed to manage life.

Conclusions

IPF affects physical activity as well as life, from onset onwards. By developing strategies for facilitating physical activity as well as identifying barriers, it seems possible to maintain an active life despite the disease. The healthcare system needs to create support systems that meet different needs during different phases of the disease.

Trial registration

“FoU in Sweden” Research and Development in Sweden (id: 227081).
Extending the intermedullary nail will not reduce the potential risk of femoral head varus in PFNA patients biomechanically: a clinical review and corresponding numerical simulation
Authors: Cha Xiaofeng , Zhou Qin , Li Jujie , Xu Hong , Xu Wenqiang , Li Jingchi
Published: May 2024

Femoral head varus is an important complication in intertrochanteric fracture patients treated with proximal femoral nail anti-rotation (PFNA) fixation. Theoretically, extending the length of the intramedullary nail could optimize fixation stability by lengthening the force arm. However, whether extending the nail length can optimize patient prognosis is unclear. In this study, a review of imaging data from intertrochanteric fracture patients with PFNA fixation was performed, and the length of the intramedullary nail in the femoral trunk and the distance between the lesser trochanter and the distal locking screw were measured. The femoral neck varus status was judged at the 6-month follow-up. The correlation coefficients between nail length and femoral neck varus angle were computed, and linear regression analysis was used to determine whether a change in nail length was an independent risk factor for femoral neck varus. Moreover, the biomechanical effects of different nail lengths on PFNA fixation stability and local stress distribution have also been verified by numerical mechanical simulations. Clinical review revealed that changes in nail length were not significantly correlated with femoral head varus and were also not an independent risk factor for this complication. In addition, only slight biomechanical changes can be observed in the numerical simulation results. Therefore, commonly used intramedullary nails should be able to meet the needs of PFNA-fixed patients, and additional procedures for longer nail insertion may be unnecessary.
Ceramic soft tissue trimming bur gingival depigmentation: clinical performance and patient experience. A split mouth randomized controlled trial
Authors: Nassar Sally K , Abuel-Ela Hala Ahmed , Fouad Yasmine Ahmed
Published: May 2024

Background

The ceramic soft tissue trimming bur (CeraTip™) was initially introduced for use in gingivoplasty but has recently been used for gingival depigmentation. The aim of this study is to compare the efficacy of depigmentation between the novel CeraTip™ and the gold-standard surgical scalpel technique.

Methods

Eight healthy, nonsmokers with moderate to severe gingival hyperpigmentation in both arches were randomly assigned for CeraTip™ depigmentation in one arch as the test group (TG) and scalpel depigmentation in the opposite arch as the control group (CG). Pigmentation indices were used to assess clinical performance. Treatment time, pain level, and esthetic satisfaction were the parameters of patient experience. The assessments were performed at baseline, one week, one month, and three months.

Results

At all assessment visits, pigmentation intensity represented by the Dummet oral pigmentation index (DOPI), and pigmentation distribution represented by the Hedin melanin index (MI), were significantly lower than those at baseline (p < 0.001) in both groups. When comparing the two groups, Scalpel depigmentation had better initial clinical outcomes, while CeraTip™ had less visible repigmentation, pain scores, treatment time, and greater esthetic satisfaction. However, none of the differences were statistically significant.

Conclusion

Both techniques successfully removed gingival hyperpigmentation with comparable clinical performance. The patients preferred CeraTip™ depigmentation.

Trial registration

The study protocol was registered on 11/09/2023 on the www.clinicaltrials.gov database (NCT06031116) after the approval of the Ethics Committee, Faculty of Dentistry, Ain Shams University (FDASU-Rec012124).
Investigating racial/ethnic differences in procedure experience in obstetrics & gynecology trainees at a single academic institution: a retrospective cohort study
Authors: GiglioAyers Patricia , Foley Christine E. , Cronin Beth , Burrell Dayna
Published: May 2024

Background

Discrimination is common in medical education. Resident physicians of races and ethnicities underrepresented in medicine experience daily discrimination which has been proven to negatively impact training. There is limited data on the impact of resident race/ethnicity on OB/GYN surgical training. The objective of this study was to investigate the impact of race/ethnicity on procedural experience in OB/GYN training.

Methods

A retrospective analysis of graduated OB/GYN resident case logs from 2009 to 2019 was performed at a single urban academic institution. Self-reported race/ethnicity data was collected. Association between URM and non-URM were analyzed using t-tests. Trainees were categorized by self-reported race/ethnicity into underrepresented in medicine (URM) (Black, Hispanic, Native American) and non-URM (White, Asian).

Results

The cohort consisted of 84 residents: 19% URM (N = 16) and 79% non-URM (n = 66). Difference between URM and non-URM status and average case volume was analyzed using t-tests. There was no difference between non-URM and URM trainees and reported mean number of Total GYN (349 vs. 334, p = 0.31) and Total OB (624 vs. 597, P = 0.11) case logs. However, compared with non-URM, on average URM performed fewer Total procedures (1562 vs. 1469, P = 0.04). Analyzing individual procedures showed a difference in average number of abortions performed between URM and non-URM (76 vs. 53, P = 0.02). There were no other statistically significant differences between the two groups.

Conclusions

This single institution study highlights potential differences in trainee experience by race/ethnicity. Larger national studies are warranted to further explore these differences to identify bias and discrimination, and to ensure equitable experience for all trainees.
Integrating the social determinants of health into graduate medical education training: a scoping review
Authors: Nour Nehal , Onchonga David , Neville Siobhan , O’Donnell Patrick , Abdalla Mohamed Elhassan
Published: May 2024

Background

The social determinants of health (SDH) play a key role in the health of individuals, communities, and populations. Academic institutions and clinical licensing bodies increasingly recognize the need for healthcare professionals to understand the importance of considering the SDH to engage with patients and manage their care effectively. However, incorporating relevant skills, knowledge, and attitudes relating to the SDH into curricula must be more consistent. This scoping review explores the integration of the SDH into graduate medical education training programs.

Methods

A systematic search was performed of PubMed, Ovid MEDLINE, ERIC, and Scopus databases for articles published between January 2010 and March 2023. A scoping review methodology was employed, and articles related to training in medical or surgical specialties for registrars and residents were included. Pilot programs, non-SDH-related programs, and studies published in languages other than English were excluded.

Results

The initial search produced 829 articles after removing duplicates. The total number of articles included in the review was 24. Most articles were from developed countries such as the USA (22), one from Canada, and only one from a low- and middle-income country, Kenya. The most highly represented discipline was pediatrics. Five papers explored the inclusion of SDH in internal medicine training, with the remaining articles covering family medicine, obstetrics, gynecology, or a combination of disciplines. Longitudinal programs are the most effective and frequently employed educational method regarding SDH in graduate training. Most programs utilize combined teaching methods and rely on participant surveys to evaluate their curriculum.

Conclusion

Applying standardized educational and evaluation strategies for SDH training programs can pose a challenge due to the diversity of the techniques reported in the literature. Exploring the most effective educational strategy in delivering these concepts and evaluating the downstream impacts on patient care, particularly in surgical and non-clinical specialties and low- and middle-income countries, can be essential in integrating and creating a sustainable healthcare force.
Challenges of care coordination for complex patients among family medicine residents in a community ambulatory clinic: a qualitative study
Authors: Heng Moses Tan Mong , Seng Gilbert Yeo Tian , Lee Eng Sing
Published: May 2024

Background

Care coordination has been identified as one of five focuses of HealthierSG. Family medicine residents are expected to collaborate with other healthcare professionals for complex patients by the end of residency. However, many residents felt that it was challenging to coordinate care effectively among healthcare stakeholders. However, to date, no qualitative studies have explored these challenges. Therefore, this study aimed to understand the challenges encountered by family medicine residents when coordinating care for complex patients.

Methods

This was a qualitative descriptive study in which semi structured in-depth interviews were conducted and guided by a topic guide. Total population sampling of 15 third-year family medicine residents in the National Healthcare Group Polyclinics was performed. The interviews were performed over Zoom and were transcribed. Thematic analysis was subsequently performed to analyse the transcripts. Coding was performed iteratively by two independent researchers. Disagreements were adjudicated by a third coder. A coding framework was agreed upon. Potential themes were then independently developed based on the coding framework.

Results

Six themes emerged from the data, namely, interprofessional communications, accessibility, personal knowledge, time constraints, patient factors and caregiver dissent.

Conclusion

Challenges faced by family medicine residents are multifaceted. While a few are systemic and pertain to the broader healthcare framework, others, such as issues of unfamiliarity with institutional workflows, community resources, and confidentiality, pertain to the microcosm of residency itself. These are reversible areas for improvement. These challenges can be addressed during planning of residency curricula to better equip family medicine residents with coordinating care for complex patients in the future.
Pass or fail: Teachers’ experience of assessment of postgraduate critical care nursing students’ competence in placement. A qualitative study
Authors: Øvrebø Line J. , Dyrstad Dagrunn Nåden , Hansen Britt Sætre
Published: May 2024

Background

Learning in placement is essential to postgraduate critical care nursing students’ education. Assessment of students’ competence in placement is important to ensure highly qualified postgraduate critical care nurses. The placement model applied in Norway involves students being assessed by a preceptor in practice and a teacher from the university. The teacher has a more distant role in placement, and the aim of this study was to explore how the teachers experience the assessment of postgraduate critical care nursing students’ competence in placement. Additionally, to explore the content of assessment documents used for postgraduate critical care nursing placement education in Norway.

Methods

This study has a qualitative design with main data collection from individual interviews with 10 teachers from eight universities and colleges in Norway. Additionally, we performed a document analysis of assessment documents from all 10 universities and colleges providing postgraduate critical care nursing education in Norway. We followed the Consolidated Criteria for Reporting Qualitative Research.

Results

The teachers experienced the assessment of postgraduate critical care nursing students’ competence in placement as important but complex, and some found it difficult to determine what critical care nursing competence is at advanced level. A thematic analysis resulted in one main theme: “Teacher facilitates the bridging between education and practice.” Furthermore, three themes were identified: “Assessment based on trust and shared responsibility”; “The teacher’s dual role as judge and supervisor”; and “A need for common, clear and relevant assessment criteria”.

Conclusions

Teachers have a key role in placement as they contribute to the bridging between education and practice by providing valuable pedagogical and academic input to the assessment process. We suggest that more teachers should be employed in joint university and clinical positions to enhance the collaboration between practice and education. Clear and relevant assessment criteria are essential for providing assessment support for both students and educators. Education and practice should collaborate on developing assessment criteria. Further, there is a need to collaborate on developing, both nationally and internationally, common, clear, relevant and user-friendly assessment tools.
Identification of mitochondria-related biomarkers in childhood allergic asthma
Authors: Zhao Wei , Fang Hongjuan , Wang Tao , Yao Chao
Published: May 2024

Background

The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. The aim of this study was to find new biomarkers related to MRGs in CAS.

Methods

This research utilized two CAS-related datasets (GSE40888 and GSE40732) and extracted 40 MRGs from the MitoCarta3.0 Database. Initially, differential expression analysis was performed on CAS and control samples in the GSE40888 dataset to obtain the differentially expressed genes (DEGs). Differentially expressed MRGs (DE-MRGs) were obtained by overlapping the DEGs and MRGs. Protein protein interactions (PPI) network of DE-MRGs was created and the top 10 genes in the degree ranking of Maximal Clique Centrality (MCC) algorithm were defined as feature genes. Hub genes were obtained from the intersection genes from the Least absolute shrinkage and selection operator (LASSO) and EXtreme Gradient Boosting (XGBoost) algorithms. Additionally, the expression validation was conducted, functional enrichment analysis, immune infiltration analysis were finished, and transcription factors (TFs)-miRNA-mRNA regulatory network was constructed.

Results

A total of 1505 DEGs were obtained from the GSE40888, and 44 DE-MRGs were obtained. A PPI network based on these 44 DE-MRGs was created and revealed strong interactions between ADCK5 and MFN1, BNIP3 and NBR1. Four hub genes (NDUFAF7, MTIF3, MRPS26, and NDUFAF1) were obtained by taking the intersection of genes from the LASSO and XGBoost algorithms based on 10 signature genes which obtained from PPI. In addition, hub genes-based alignment diagram showed good diagnostic performance. The results of Gene Set Enrichment Analysis (GSEA) suggested that hub genes were closely related to mismatch repair. The B cells naive cells were significantly expressed between CAS and control groups, and MTIF3 was most strongly negatively correlated with B cells naive. In addition, the expression of MTIF3 and MRPS26 may have influenced the inflammatory response in CAS patients by affecting mitochondria-related functions. The quantitative real-time polymerase chain reaction (qRT‒PCR) results showed that four hub genes were all down-regulated in the CAS samples.

Conclusion

NDUFAF7, MTIF3, MRPS26, and NDUFAF1 were identified as an MRGs-related biomarkers in CAS, which provides some reference for further research on CAS.
Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies
Authors: Yin Jia-Li , Yang Jing , Song Xin-Jian , Qin Xue , Chang Yu-Jiao , Chen Xing , Liu Fang-Hua , Li Yi-Zi , Xu He-Li , Wei Yi-Fan , Cao Fan , Bai Xue-Li , Wu Lang , Tao Tao , Du Jian , Gong Ting-Ting , Wu Qi-Jun
Published: May 2024

Background

Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence.

Methods

A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587).

Results

Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index.

Conclusion

We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.
Exploring class III cellobiose dehydrogenase: sequence analysis and optimized recombinant expression
Authors: Giorgianni Angela , Zenone Alice , Sützl Leander , Csarman Florian , Ludwig Roland
Published: May 2024

Background

Cellobiose dehydrogenase (CDH) is an extracellular fungal oxidoreductase with multiple functions in plant biomass degradation. Its primary function as an auxiliary enzyme of lytic polysaccharide monooxygenase (LPMO) facilitates the efficient depolymerization of cellulose, hemicelluloses and other carbohydrate-based polymers. The synergistic action of CDH and LPMO that supports biomass-degrading hydrolases holds significant promise to harness renewable resources for the production of biofuels, chemicals, and modified materials in an environmentally sustainable manner. While previous phylogenetic analyses have identified four distinct classes of CDHs, only class I and II have been biochemically characterized so far.

Results

Following a comprehensive database search aimed at identifying CDH sequences belonging to the so far uncharacterized class III for subsequent expression and biochemical characterization, we have curated an extensive compilation of putative CDH amino acid sequences. A sequence similarity network analysis was used to cluster them into the four distinct CDH classes. A total of 1237 sequences encoding putative class III CDHs were extracted from the network and used for phylogenetic analyses. The obtained phylogenetic tree was used to guide the selection of 11 cdhIII genes for recombinant expression in Komagataella phaffii. A small-scale expression screening procedure identified a promising cdhIII gene originating from the plant pathogen Fusarium solani (FsCDH), which was selected for expression optimization by signal peptide shuffling and subsequent production in a 5-L bioreactor. The purified FsCDH exhibits a UV-Vis spectrum and enzymatic activity similar to other characterized CDH classes.

Conclusion

The successful production and functional characterization of FsCDH proved that class III CDHs are catalytical active enzymes resembling the key properties of class I and class II CDHs. A detailed biochemical characterization based on the established expression and purification strategy can provide new insights into the evolutionary process shaping CDHs and leading to their differentiation into the four distinct classes. The findings have the potential to broaden our understanding of the biocatalytic application of CDH and LPMO for the oxidative depolymerization of polysaccharides.
Fermentative aminopyrrolnitrin production by metabolically engineered Corynebacterium glutamicum
Authors: Putri Virginia Ryandini Melati , Jung Min-Hee , Lee Ji-Young , Kwak Mi-Hyang , Mariyes Theavita Chatarina , Kerbs Anastasia , Wendisch Volker F. , Kong Hee Jeong , Kim Young-Ok , Lee Jin-Ho
Published: May 2024

Aminopyrrolnitrin (APRN), a natural halogenated phenylpyrrole derivative (HPD), has strong antifungal and antiparasitic activities. Additionally, it showed 2.8-fold increased photostability compared to pyrrolnitrin, a commercially available HPD with antimicrobial activity. For microbial production of APRN, we first engineered anthranilate phosphoribosyltransferase encoded by trpD from Corynebacterium glutamicum, resulting in a TrpDA162D mutation that exhibits feedback-resistant against l-tryptophan and higher substrate affinity compared to wild-type TrpD. Plasmid-borne expression of trpDA162D in C. glutamicum TP851 strain with two copies of trpDA162D in the genome led to the production of 3.1 g/L l-tryptophan in flask culture. Subsequent step for l-tryptophan chlorination into 7-chloro-l-tryptophan was achieved by introducing diverse sources of genes encoding tryptophan 7-halogenase (PrnA or RebH) and flavin reductase (Fre, PrnF, or RebF). The combined expression of prnA from Serratia grimesii or Serratia plymuthica with flavin reductase gene from Escherichia coli, Pseudomonas fluorescens, or Lechevalieria aerocolonigenes yielded higher production of 7-chloro-l-tryptophan in comparison to other sets of two-component systems. In the next step, production of putative monodechloroaminopyrrolnitrin (MDAP) from 7-chloro-l-tryptophan was achieved through the expression of prnB encoding MDAP synthase from S. plymuthica or P. fluorescens. Finally, an artificial APRN biosynthetic pathway was constructed by simultaneously expressing genes coding for tryptophan 7-halogenase, flavin reductase, MDAP synthase, and MDAP halogenase (PrnC) from different microbial sources within the l-tryptophan-producing TP851 strain. As prnC from S. grimesii or S. plymuthica was introduced into the host strain, which carried plasmids expressing prnA from S. plymuthica, fre from E. coli, and prnB from S. plymuthica, APN3639 and APN3638 accumulated 29.5 mg/L and 28.1 mg/L of APRN in the culture broth. This study represents the first report on the fermentative APRN production by metabolically engineered C. glutamicum.
NEK2 contributes to radioresistance in esophageal squamous cell carcinoma by inducing protective autophagy via regulating TRIM21
Authors: Guo Dong , Zhou Shuo , Liu Ruixue , Yao Weinan , Li Shuguang , Zhang Xueyuan , Shen Wenbin , Zhu Shuchai
Published: May 2024

Background

Radiotherapy (RT) has been identified as a vital treatment for esophageal squamous cell carcinoma (ESCC), while the development of radioresistance remains a major obstacle in ESCC management. The aim of this study was to investigate the effect of NIMA-related kinase 2 (NEK2) on radioresistance in ESCC cells and to reveal potential molecular mechanisms.

Methods

Human esophageal epithelial cells (HEEC) and human ESCC cell lines were obtained from the Research Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Cell Counting Kit-8 (CCK-8) and flow cytometry assays were applied to assess the proliferation ability, cell cycle, apoptosis rates, and ROS production of ESCC cells. The colony-forming assay was used to estimate the effect of NEK2 on radiosensitivity. Autophagy was investigated by western blotting analysis, GFP-mRFP-LC3 fluorescence assay, and transmission electron microscopy (TEM).

Results

In the present study, our results showed that NEK2 was associated with radioresistance, cell cycle arrest, apoptosis, ROS production, and survival of ESCC. NEK2 knockdown could significantly inhibit growth while enhancing radiosensitivity and ROS production in ESCC cells. Interestingly, NEK2 knockdown inhibited ESCC cell autophagy and reduced autophagic flux, ultimately reversing NEK2-induced radioresistance. Mechanistically, NEK2 bound to and regulated the stability of tripartite motif-containing protein 21 (TRIM21). The accumulation of NEK2-induced light chain 3 beta 2 (LC3B II) can be reversed by the knockdown of TRIM21.

Conclusion

These results demonstrated that NEK2 activated autophagy through TRIM21, which may provide a promising therapeutic strategy for elucidating NEK2-mediated radioresistance in ESCC.
Action against inequalities: a synthesis of social justice & equity, diversity, inclusion frameworks
Authors: Hayvon John C.
Published: May 2024

Inequalities in health have long been recognized as interconnected with social, economic, and various other inequalities. The application of social justice and equity, diversity, inclusion (EDI) frameworks may help expand interdisciplinary perspectives in addressing inequalities. This review study conducted an environmental scan for existing syntheses of theories, models, and frameworks (TMFs) relevant to the social justice and EDI. Results from Web of Science, Scopus, PubMed, CINAHL, PsychINFO, and MEDLINE retrieved an existing implementation science framework intently centered upon health inequalities, and draws from a synthesis of postcolonial theory, reflexivity, intersectionality, structural violence, and governance theory. Given this high degree of relevance to the objective of this review, the framework was selected as a basis for expanded synthesis. Subsequent processes sought to identify social justice TMFs which could be integrated into the base framework selected, as well as to refine scope of the study. Based upon considerations of level of evidence and non-tokenistic integration, the following social justice and EDI TMFs were identified: John Rawls’ theory of justice; Amartya Sen’s Capabilities Approach; Iris Marion Young’s theories of justice; Paulo Freire’s critical consciousness; and critical race theory (CRT). The focus of the synthesis performed was scoped towards minimizing potential harms arising from actions intending to reduce inequalities. EDI considerations were not collated into a singular construct, but rather extended as a separate component assessing inequitable distribution of risks and benefits given population heterogeneity. Reflexive analysis amended the framework with two key decisions: first, the integration of environmental justice into a single construct, which helps to inform Rawls’ and Sen’s TMFs; second, a temporal element of sequential-analysis was employed over a unified output. The result of synthesis consists of a three-component framework which: (1) presents sixteen constructs drawn from selected TMFs, to consider various harms or potential reinforcement of existing inequalities; (2) aims to de-invisibilize marginalized groups who are noted to experience inequitable outcomes, and acknowledges the presence of individuals belonging to multiple groups; and (3) synthesizes seven considerations related to equitable dissemination and evaluation as drawn from TMFs, separated for sequential analysis after assessment of harms.
Clinical outcomes of single blastocyst transfer with machine learning guided noninvasive chromosome screening grading system in infertile patients
Authors: Li Xiaoxi , Yao Yaxin , Zhao Dunmei , Chang Xiufeng , Li Yi , Lin Huilan , Wei Huijuan , Wang Haiye , Mi Ying , Huang Lei , Lu Sijia , Yang Weimin , Cai Liyi
Published: May 2024

Background

Prospective observational studies have demonstrated that the machine learning (ML) -guided noninvasive chromosome screening (NICS) grading system, which we called the noninvasive chromosome screening-artificial intelligence (NICS-AI) grading system, can be used embryo selection. The current prospective interventional clinical study was conducted to investigate whether this NICS-AI grading system can be used as a powerful tool for embryo selection.

Methods

Patients who visited our centre between October 2018 and December 2021 were recruited. Grade A and B embryos with a high probability of euploidy were transferred in the NICS group. The patients in the control group selected the embryos according to the traditional morphological grading. Finally, 90 patients in the NICS group and 161 patients in the control group were compared statistically for their clinical outcomes.

Results

In the NICS group, the clinical pregnancy rate (70.0% vs. 54.0%, p < 0.001), the ongoing pregnancy rate (58.9% vs. 44.7%, p = 0.001), and the live birth rate (56.7% vs. 42.9%, p = 0.001) were significantly higher than those of the control group. When the female was ≥ 35 years old, the clinical pregnancy rate (67.7% vs. 32.1%, p < 0.001), ongoing pregnancy rate (56.5% vs. 25.0%, p = 0.001), and live birth rate (54.8% vs. 25.0%, p = 0.001) in the NICS group were significantly higher than those of the control group. Regardless of whether the patients had a previous record of early spontaneous abortion or not, the live birth rate of the NICS group was higher than that of the control group (61.0% vs. 46.9%; 57.9% vs. 34.8%; 33.3% vs. 0%) but the differences were not statistically significant.

Conclusions

NICS-AI was able to improve embryo utilisation rate, and the live birth rate, especially for those ≥ 35 years old, with transfer of Grade A embryos being preferred, followed by Grade B embryos. NICS-AI can be used as an effective tool for embryo selection in the future.
Evaluation of a low-cost staining method for improved visualization of sweet potato whitefly (Bemisia tabaci) eggs on multiple crop plant species
Authors: van Raalte Benjamin , Watrous Kristal , Lujan Miguel , Le Ricky , Sun Penglin , Ellis Benjamin , Mauck Kerry E.
Published: May 2024

Background

The sweet potato whitefly (Bemisia tabaci) is a globally important insect pest that damages crops through direct feeding and by transmitting viruses. Current B. tabaci management revolves around the use of insecticides, which are economically and environmentally costly. Host plant resistance is a sustainable option to reduce the impact of whiteflies, but progress in deploying resistance in crops has been slow. A major obstacle is the high cost and low throughput of screening plants for B. tabaci resistance. Oviposition rate is a popular metric for host plant resistance to B. tabaci because it does not require tracking insect development through the entire life cycle, but accurate quantification is still limited by difficulties in observing B. tabaci eggs, which are microscopic and translucent. The goal of our study was to improve quantification of B. tabaci eggs on several important crop species: cassava, cowpea, melon, sweet potato and tomato.

Results

We tested a selective staining process originally developed for leafhopper eggs: submerging the leaves in McBryde’s stain (acetic acid, ethanol, 0.2% aqueous acid Fuchsin, water; 20:19:2:1) for three days, followed by clearing under heat and pressure for 15 min in clearing solution (LGW; lactic acid, glycerol, water; 17:20:23). With a less experienced individual counting the eggs, B. tabaci egg counts increased after staining across all five crops. With a more experienced counter, egg counts increased after staining on melons, tomatoes, and cowpeas. For all five crops, there was significantly greater agreement on egg counts across the two counting individuals after the staining process. The staining method worked particularly well on melon, where egg counts universally increased after staining for both counting individuals.

Conclusions

Selective staining aids visualization of B. tabaci eggs across multiple crop plants, particularly species where leaf morphological features obscure eggs, such as melons and tomatoes. This method is broadly applicable to research questions requiring accurate quantification of B. tabaci eggs, including phenotyping for B. tabaci resistance.
MNMST: topology of cell networks leverages identification of spatial domains from spatial transcriptomics data
Authors: Wang Yu , Liu Zaiyi , Ma Xiaoke
Published: May 2024

Advances in spatial transcriptomics provide an unprecedented opportunity to reveal the structure and function of biology systems. However, current algorithms fail to address the heterogeneity and interpretability of spatial transcriptomics data. Here, we present a multi-layer network model for identifying spatial domains in spatial transcriptomics data with joint learning. We demonstrate that spatial domains can be precisely characterized and discriminated by the topological structure of cell networks, facilitating identification and interpretability of spatial domains, which outperforms state-of-the-art baselines. Furthermore, we prove that network model offers an effective and efficient strategy for integrative analysis of spatial transcriptomics data from various platforms.
In vivo rescue of genetic dilated cardiomyopathy by systemic delivery of nexilin
Authors: Shao Yanjiao , Liu Canzhao , Liao Hsin-Kai , Zhang Ran , Yuan Baolei , Yang Hanyan , Li Ronghui , Zhu Siting , Fang Xi , Rodriguez Esteban Concepcion , Chen Ju , Izpisua Belmonte Juan Carlos
Published: May 2024

Background

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Multiple identified mutations in nexilin (NEXN) have been suggested to be linked with severe DCM. However, the exact association between multiple mutations of Nexn and DCM remains unclear. Moreover, it is critical for the development of precise and effective therapeutics in treatments of DCM.

Results

In our study, Nexn global knockout mice and mice carrying human equivalent G645del mutation are studied using functional gene rescue assays. AAV-mediated gene delivery is conducted through systemic intravenous injections at the neonatal stage. Heart tissues are analyzed by immunoblots, and functions are assessed by echocardiography. Here, we identify functional components of Nexilin and demonstrate that exogenous introduction could rescue the cardiac function and extend the lifespan of Nexn knockout mouse models. Similar therapeutic effects are also obtained in G645del mice, providing a promising intervention for future clinical therapeutics.

Conclusions

In summary, we demonstrated that a single injection of AAV-Nexn was capable to restore the functions of cardiomyocytes and extended the lifespan of Nexn knockout and G645del mice. Our study represented a long-term gene replacement therapy for DCM that potentially covers all forms of loss-of-function mutations in NEXN.
The influence of oviposition status on measures of transmission potential in malaria-infected mosquitoes depends on sugar availability
Authors: Shiau Justine C. , Garcia-Diaz Nathan , Kyle Dennis E. , Pathak Ashutosh K.
Published: May 2024

Background

Like other oviparous organisms, the gonotrophic cycle of mosquitoes is not complete until they have selected a suitable habitat to oviposit. In addition to the evolutionary constraints associated with selective oviposition behavior, the physiological demands relative to an organism’s oviposition status also influence their nutrient requirement from the environment. Yet, studies that measure transmission potential (vectorial capacity or competence) of mosquito-borne parasites rarely consider whether the rates of parasite replication and development could be influenced by these constraints resulting from whether mosquitoes have completed their gonotrophic cycle.

Methods

Anopheles stephensi mosquitoes were infected with Plasmodium berghei, the rodent analog of human malaria, and maintained on 1% or 10% dextrose and either provided oviposition sites (‘oviposited’ herein) to complete their gonotrophic cycle or forced to retain eggs (‘non-oviposited’). Transmission potential in the four groups was measured up to 27 days post-infection as the rates of (i) sporozoite appearance in the salivary glands (‘extrinsic incubation period' or EIP), (ii) vector survival and (iii) sporozoite densities.

Results

In the two groups of oviposited mosquitoes, rates of sporozoite appearance and densities in the salivary glands were clearly dependent on sugar availability, with shorter EIP and higher sporozoite densities in mosquitoes fed 10% dextrose. In contrast, rates of appearance and densities in the salivary glands were independent of sugar concentrations in non-oviposited mosquitoes, although both measures were slightly lower than in oviposited mosquitoes fed 10% dextrose. Vector survival was higher in non-oviposited mosquitoes.

Conclusions

Costs to parasite fitness and vector survival were buffered against changes in nutritional availability from the environment in non-oviposited but not oviposited mosquitoes. Taken together, these results suggest vectorial capacity for malaria parasites may be dependent on nutrient availability and oviposition/gonotrophic status and, as such, argue for more careful consideration of this interaction when estimating transmission potential. More broadly, the complex patterns resulting from physiological (nutrition) and evolutionary (egg-retention) trade-offs described here, combined with the ubiquity of selective oviposition behavior, implies the fitness of vector-borne pathogens could be shaped by selection for these traits, with implications for disease transmission and management. For instance, while reducing availability of oviposition sites and environmental sources of nutrition are key components of integrated vector management strategies, their abundance and distribution are under strong selection pressure from the patterns associated with climate change.

Graphical Abstract
From compartments to loops: understanding the unique chromatin organization in neuronal cells
Authors: Zagirova Diana , Kononkova Anna , Vaulin Nikita , Khrameeva Ekaterina
Published: May 2024

The three-dimensional organization of the genome plays a central role in the regulation of cellular functions, particularly in the human brain. This review explores the intricacies of chromatin organization, highlighting the distinct structural patterns observed between neuronal and non-neuronal brain cells. We integrate findings from recent studies to elucidate the characteristics of various levels of chromatin organization, from differential compartmentalization and topologically associating domains (TADs) to chromatin loop formation. By defining the unique chromatin landscapes of neuronal and non-neuronal brain cells, these distinct structures contribute to the regulation of gene expression specific to each cell type. In particular, we discuss potential functional implications of unique neuronal chromatin organization characteristics, such as weaker compartmentalization, neuron-specific TAD boundaries enriched with active histone marks, and an increased number of chromatin loops. Additionally, we explore the role of Polycomb group (PcG) proteins in shaping cell-type-specific chromatin patterns. This review further emphasizes the impact of variations in chromatin architecture between neuronal and non-neuronal cells on brain development and the onset of neurological disorders. It highlights the need for further research to elucidate the details of chromatin organization in the human brain in order to unravel the complexities of brain function and the genetic mechanisms underlying neurological disorders. This research will help bridge a significant gap in our comprehension of the interplay between chromatin structure and cell functions.
Targeting pathogenic fibroblast-like synoviocyte subsets in rheumatoid arthritis
Authors: Qian Hongyan , Deng Chaoqiong , Chen Shiju , Zhang Xinwei , He Yan , Lan Jingying , Wang Aodi , Shi Guixiu , Liu Yuan
Published: May 2024

Fibroblast-like synoviocytes (FLSs) play a central role in RA pathogenesis and are the main cellular component in the inflamed synovium of patients with rheumatoid arthritis (RA). FLSs are emerging as promising new therapeutic targets in RA. However, fibroblasts perform many essential functions that are required for sustaining tissue homeostasis. Direct targeting of general fibroblast markers on FLSs is challenging because fibroblasts in other tissues might be altered and side effects such as reduced wound healing or fibrosis can occur. To date, no FLS-specific targeted therapies have been applied in the clinical management of RA. With the help of high-throughput technologies such as scRNA-seq in recent years, several specific pathogenic FLS subsets in RA have been identified. Understanding the characteristics of these pathogenic FLS clusters and the mechanisms that drive their differentiation can provide new insights into the development of novel FLS-targeting strategies for RA. Here, we discuss the pathogenic FLS subsets in RA that have been elucidated in recent years and potential strategies for targeting pathogenic FLSs.
Potential clinical application of anti-Müllerian hormone testing in radioiodine treatment of thyroid carcinoma
Authors: Havlínová Barbora , Součková Ilona , Kopřivová Kateřina , Doležal Jiří
Published: May 2024

Differentiated thyroid cancer is the most common endocrinological malignancy. Radioiodine treatment has a clear benefit in locally aggressive and metastatic cancers. There are discussions about long-term and acute adverse events.

Anti-Müllerian hormone is regarded as the best endocrine marker for evaluating the physiological loss of oocytes in healthy women with regard to age. The impact of radioiodine treatment on anti-Müllerian hormone levels has been more significantly reported in patients over 35 years of age. About reproductive dysfunction, calculations of individual absorbed doses of radioiodine in ovaries after thyroid cancer therapy have not been performed yet. The aim of our ongoing prospective study is to determine serum anti-Müllerian hormone to estimate ovarian reserve for premenopausal women treated with radioiodine and to compare anti-Müllerian hormone levels before and after radioiodine treatment. Predicting radioiodine side effects by evaluating a simple serum biomarker may help to select an appropriate treatment strategy for young women planning pregnancy, specifically in the assessment of ovarian reserve and premature ovarian failure with early onset of menopause.
Geography and health: role of human translocation and access to care
Authors: Brattig Norbert , Bergquist Robert , Vienneau Danielle , Zhou Xiao-Nong
Published: May 2024

Natural, geographical barriers have historically limited the spread of communicable diseases. This is no longer the case in today’s interconnected world, paired with its unprecedented environmental and climate change, emphasising the intersection of evolutionary biology, epidemiology and geography (i.e. biogeography). A total of 14 articles of the special issue entitled “Geography and health: role of human translocation and access to care” document enhanced disease transmission of diseases, such as malaria, leishmaniasis, schistosomiasis, COVID-19 (Severe acute respiratory syndrome corona 2) and Oropouche fever in spite of spatiotemporal surveillance. High-resolution satellite images can be used to understand spatial distributions of transmission risks and disease spread and to highlight the major avenue increasing the incidence and geographic range of zoonoses represented by spill-over transmission of coronaviruses from bats to pigs or civets. Climate change and globalization have increased the spread and establishment of invasive mosquitoes in non-tropical areas leading to emerging outbreaks of infections warranting improved physical, chemical and biological vector control strategies. The translocation of pathogens and their vectors is closely connected with human mobility, migration and the global transport of goods. Other contributing factors are deforestation with urbanization encroaching into wildlife zones. The destruction of natural ecosystems, coupled with low income and socioeconomic status, increase transmission probability of neglected tropical and zoonotic diseases. The articles in this special issue document emerging or re-emerging diseases and surveillance of fever symptoms. Health equity is intricately connected to accessibility to health care and the targeting of healthcare resources, necessitating a spatial approach. Public health comprises successful disease management integrating spatial surveillance systems, including access to sanitation facilities. Antimicrobial resistance caused, e.g. by increased use of antibiotics in health, agriculture and aquaculture, or acquisition of resistance genes, can be spread by horizontal gene transfer. This editorial reviews the key findings of this 14-article special issue, identifies important gaps relevant to our interconnected world and makes a number of specific recommendations to mitigate the transmission risks of infectious diseases in the post-COVID-19 pandemic era.