bluuebunny/crossref_metadata_2025 huggingface dataset:
The IL-7R antagonist lusvertikimab reduces leukemic burden in xenograft ALL via antibody-dependent cellular phagocytosis
Authors: Lenk Lennart , Baccelli Irène , Laqua Anna , Heymann Julia , Reimer Claas , Dietterle Anna , Winterberg Dorothee , Mary Caroline , Corallo Frédérique , Taurelle Julien , Narbeburu Emma , Neyton Stéphanie , Déramé Mylène , Pengam Sabrina , Vogiatzi Fotini , Bornhauser Beat , Bourquin Jean-Pierre , Raffel Simon , Dovhan Vladyslava , Schüler Thomas , Escherich Gabriele , den Boer Monique L. , Boer Judith M. , Wessels Wiebke , Peipp Matthias , Alten Julia , Antić Željko , Bergmann Anke K. , Schrappe Martin , Cario Gunnar , Brüggemann Monika , Poirier Nicolas , Schewe Denis M.
Published: March 2024

Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of B-cell precursors (BCP-ALL) or T cells (T-ALL). Current treatment protocols obtain high cure rates in children but are based on toxic polychemotherapy. Novel therapies are urgently needed, especially in relapsed/refractory (R/R) disease, high-risk (HR) leukemias and T-ALL, in which immunotherapy approaches remain scarce. Although the interleukin-7 receptor (IL-7R) plays a pivotal role in ALL development, no IL-7R–targeting immunotherapy has yet reached clinical application in ALL. The IL-7Rα chain (CD127)–targeting IgG4 antibody lusvertikimab (LUSV; formerly OSE-127) is a full antagonist of the IL-7R pathway, showing a good safety profile in healthy volunteers. Here, we show that ∼85% of ALL cases express surface CD127. We demonstrate significant in vivo efficacy of LUSV immunotherapy in a heterogeneous cohort of BCP- and T-ALL patient-derived xenografts (PDX) in minimal residual disease (MRD) and overt leukemia models, including R/R and HR leukemias. Importantly, LUSV was particularly effective when combined with polychemotherapy in a phase 2-like PDX study with CD127high samples leading to MRD-negativity in >50% of mice treated with combination therapy. Mechanistically, LUSV targeted ALL cells via a dual mode of action comprising direct IL-7R antagonistic activity and induction of macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). LUSV–mediated in vitro ADCP levels significantly correlated with CD127 expression levels and the reduction of leukemia burden upon treatment of PDX animals in vivo. Altogether, through its dual mode of action and good safety profile, LUSV may represent a novel immunotherapy option for any CD127+ ALL, particularly in combination with standard-of-care polychemotherapy.
Endothelial ZIP8 plays a minor role in BMP6 regulation by iron in mice
Authors: Fisher Allison L. , Phillips Sydney , Wang Chia-Yu , Paulo Joao A. , Xiao Xia , Moschetta Gillian A. , Sridhar Adhvaith , Mancias Joseph D. , Babitt Jodie L.
Published: March 2024

Iron-mediated induction of bone morphogenetic protein (BMP)6 expression by liver endothelial cells is essential for iron homeostasis regulation. We used multiple dietary and genetic mouse cohorts to demonstrate a minor functional role for the metal-ion transporter ZIP8 in regulating BMP6 expression under high-iron conditions.
Vascular smooth muscle cells in response to cholesterol crystals modulates inflammatory cytokines release and promotes neutrophil extracellular trap formation
Authors: Thazhathveettil Jishamol , Kumawat Ashok Kumar , Demirel Isak , Sirsjö Allan , Paramel Geena Varghese
Published: March 2024

Background

The formation and accumulation of cholesterol crystals (CC) at the lesion site is a hallmark of atherosclerosis. Although studies have shown the importance of vascular smooth muscle cells (VSMCs) in the disease atherosclerosis, little is known about the molecular mechanism behind the uptake of CC in VSMCs and their role in modulating immune response.

Methods

Human aortic smooth muscle cells were cultured and treated with CC. CC uptake and CC mediated signaling pathway and protein induction were studied using flow cytometry, confocal microscopy, western blot and Olink proteomics. Conditioned medium from CC treated VSMCs was used to study neutrophil adhesion, ROS production and phagocytosis. Neutrophil extracellular traps (NETs) formations were visualized using confocal microscopy.

Results

VSMCs and macrophages were found around CC clefts in human carotid plaques. CC uptake in VSMCs are largely through micropinocytosis and phagocytosis via PI3K–AkT dependent pathway. The uptake of CC in VSMCs induce the release inflammatory proteins, including IL-33, an alarming cytokine. Conditioned medium from CC treated VSMCs can induce neutrophil adhesion, neutrophil reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) formation. IL-33 neutralization in conditioned medium from CC treated VSMCs inhibited neutrophil ROS production and NETs formation.

Conclusion

We demonstrate that VSMCs due to its vicinity to CC clefts in human atherosclerotic lesion can modulate local immune response and we further reveal that the interaction between CC and VSMCs impart an inflammatory milieu in the atherosclerotic microenvironment by promoting IL-33 dependent neutrophil influx and NETs formation.
A case of Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim
Authors: Dong Michael , Pearce Fiona , Singh Nandini , Lin Ming-Lee
Published: March 2024

Purpose

To report a case of endogenous Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim.

Case report

A 57-year-old man developed disseminated Lomentospora prolificans with right endophthalmitis on the background of immunosuppression following lung transplantation for interstitial lung disease. He was treated with early vitrectomy, intravitreal voriconazole, and systemic Olorofim, voriconazole and terbinafine. His symptoms improved and remained stable in the right eye. Eight weeks later the patient represented with Lomentopora prolificans endophthalmitis in the left eye when systemic voriconazole and terbinafine treatment were withdrawn. Despite aggressive treatment he ultimately succumbed due to vascular complications of extensive disseminated disease.

Conclusion

We report a rare case of disseminated Lomentosporosis with panophthalmitis in an immunocompromised host with prolonged survival on systemic Olorofim, voriconazole and terbinafine in conjunction with pars plana vitrectomy and intravitreal voriconazole. Early suspicion of an opportunistic fungal infection is critical, as managing disseminated disease is often unsuccessful. Despite presumed inherent resistance, intravitreal and systemic voriconazole appeared to limit disease progression in the right eye. The potential synergistic effects of combined antifungal therapy with orotomides warrant further investigation.
An evolutionary view of the Fusarium core genome
Authors: Gomez-Chavarria Daniel A. , Rua-Giraldo Alvaro L. , Alzate Juan F.
Published: March 2024

Fusarium, a member of the Ascomycota fungi, encompasses several pathogenic species significant to plants and animals. Some phytopathogenic species have received special attention due to their negative economic impact on the agricultural industry around the world. Traditionally, identification and taxonomic analysis of Fusarium have relied on morphological and phenotypic features, including the fungal host, leading to taxonomic conflicts that have been solved using molecular systematic technologies. In this work, we applied a phylogenomic approach that allowed us to resolve the evolutionary history of the species complexes of the genus and present evidence that supports the F. ventricosum species complex as the most basal lineage of the genus. Additionally, we present evidence that proposes modifications to the previous hypothesis of the evolutionary history of the F. staphyleae, F. newnesense, F. nisikadoi, F. oxysporum, and F. fujikuroi species complexes. Evolutionary analysis showed that the genome GC content tends to be lower in more modern lineages, in both, the whole-genome and core-genome coding DNA sequences. In contrast, genome size gain and losses are present during the evolution of the genus. Interestingly, core genome duplication events positively correlate with genome size. Evolutionary and genome conservation analysis supports the F3 hypothesis of Fusarium as a more compact and conserved group in terms of genome conservation. By contrast, outside of the F3 hypothesis, the most basal clades only share 8.8% of its genomic sequences with the F3 clade.
Development and validation of a Radiopathomics model based on CT scans and whole slide images for discriminating between Stage I-II and Stage III gastric cancer
Authors: Tan Yang , Feng Li-juan , Huang Ying-he , Xue Jia-wen , Feng Zhen-Bo , Long Li-ling
Published: March 2024

Objective

This study aimed to develop and validate an artificial intelligence radiopathological model using preoperative CT scans and postoperative hematoxylin and eosin (HE) stained slides to predict the pathological staging of gastric cancer (stage I-II and stage III).

Methods

This study included a total of 202 gastric cancer patients with confirmed pathological staging (training cohort: n = 141; validation cohort: n = 61). Pathological histological features were extracted from HE slides, and pathological models were constructed using logistic regression (LR), support vector machine (SVM), and NaiveBayes. The optimal pathological model was selected through receiver operating characteristic (ROC) curve analysis. Machine learnin algorithms were employed to construct radiomic models and radiopathological models using the optimal pathological model. Model performance was evaluated using ROC curve analysis, and clinical utility was estimated using decision curve analysis (DCA).

Results

A total of 311 pathological histological features were extracted from the HE images, including 101 Term Frequency-Inverse Document Frequency (TF-IDF) features and 210 deep learning features. A pathological model was constructed using 19 selected pathological features through dimension reduction, with the SVM model demonstrating superior predictive performance (AUC, training cohort: 0.949; validation cohort: 0.777). Radiomic features were constructed using 6 selected features from 1834 radiomic features extracted from CT scans via SVM machine algorithm. Simultaneously, a radiopathomics model was built using 17 non-zero coefficient features obtained through dimension reduction from a total of 2145 features (combining both radiomics and pathomics features). The best discriminative ability was observed in the SVM_radiopathomics model (AUC, training cohort: 0.953; validation cohort: 0.851), and clinical decision curve analysis (DCA) demonstrated excellent clinical utility.

Conclusion

The radiopathomics model, combining pathological and radiomic features, exhibited superior performance in distinguishing between stage I-II and stage III gastric cancer. This study is based on the prediction of pathological staging using pathological tissue slides from surgical specimens after gastric cancer curative surgery and preoperative CT images, highlighting the feasibility of conducting research on pathological staging using pathological slides and CT images.
Incidence rates of retinal vascular occlusive diseases from 2011 to 2020 in South Korea: a nationwide cohort study
Authors: Park Shin Hyeong , Kim Bum Jun , Kim Ji Hye , Kim Seung Chan , Kim Rock Bum , Han Yong Seop
Published: March 2024

Background

Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea.

Methods

This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates.

Results

We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18–70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06–2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79–51.19) cases/100,000 person-years.

Conclusion

The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75–79 years for total retinal vascular occlusion and retinal vein occlusion, and 80–85 years for central retinal artery occlusion.
Key predictors of food security and nutrition in Africa: a spatio-temporal model-based study
Authors: Bofa Adusei , Zewotir Temesgen
Published: March 2024

There is voluminous literature on Food Security in Africa. This study explicitly considers the spatio-temporal factors in addition to the usual FAO-based metrics in modeling and understanding the dynamics of food security and nutrition across the African continent. To better understand the complex trajectory and burden of food insecurity and nutrition in Africa, it is crucial to consider space-time factors when modeling and interpreting food security. The spatio-temporal anova model was found to be superior(employing statistical criteria) to the other three models from the spatio-temporal interaction domain models. The results of the study suggest that dietary supply adequacy, food stability, and consumption status are positively associated with severe food security, while average food supply and environmental factors have negative effects on Food Security and Nutrition. The findings also indicate that severe food insecurity and malnutrition are spatially and temporally correlated across the African continent. Spatio-temporal modeling and spatial mapping are essential components of a comprehensive practice to reduce the burden of severe food insecurity. likewise, any planning and intervention to improve the average food supply and environment to promote sustainable development should be regional instead of one size fit all.
Clinical skills development for healthcare practitioners working with patients with persistent physical symptoms (PPS) in healthcare settings: a systematic review and narrative synthesis
Authors: Thursby Stacie , Dismore Lorelle , Swainston Katherine
Published: March 2024

Background

The complexity and uncertainty around Persistent Physical Symptoms (PPS) make it difficult to diagnose and treat, particularly under time-constrained consultations and limited knowledge. Brief interventions that can be utilised in day-to-day practice are necessary to improve ways of managing PPS. This review aimed to establish (i) what training primary and secondary healthcare practitioners have undertaken to develop their clinical skills when working with PPS, (ii) what training techniques or theoretical models have been used within these interventions, and (iii) how effective was the training.

Method

A systematic literature search was undertaken on eight databases to identify professional development interventions for healthcare practitioners working with PPS, were of any study design, and at a minimum were single measure studies (i.e., training outcome alone). Studies were assessed using the Mixed Methods Appraisal Tool (MMAT) and narratively synthesised.

Results

Despite high methodological heterogeneity across the six included studies, they all aimed to improve healthcare practitioners’ communication skills through educational (theory, awareness, attitudes, assessment, treatment, and management of PPS) and experiential (role play) learning.

Conclusions

The review findings demonstrate that developing healthcare practitioners’ communicative behaviours led to increased confidence and self-efficacy when working with PPS, which facilitated improved consultations and improvements on some patient outcomes. Barriers to the uptake of training programmes and implementation into daily clinical practice are discussed, including the need for PPS to be formally implemented into undergraduate teaching and post-qualification continuous professional development.

Trial registration

This review was registered at PROSPERO [CRD42022315631] prior to the review starting.
Validation study of the Amharic version Safety Attitudes Questionnaire (SAQ) in public hospitals of Addis Ababa, Ethiopia: a cross-sectional study
Authors: Bekele Bisrat Tamene , Berhe Trhas Tadesse , Wotango Biniam Yohannes , Workneh Wubet Mihretu , Wendwessen Nebiyou
Published: March 2024

Background

In Ethiopia, there is a growing concern about improving patients’ safety in healthcare facilities. However, the lack of a valid and reliable instrument sensitive to the Ethiopian culture for measuring health professional practice environment leads to difficulty in constructing evaluations of safety climate and further linking organizational research to outcomes research. This research study examined the psychometric properties of the Safety Attitude Questionnaire (SAQ) in the Amharic language within an Ethiopian healthcare context.

Method

A hospital-based cross-sectional study design was conducted. The SAQ was meticulously translated into Amharic using forward and backward translation methods. Content validity was evaluated with input from seven patient safety and healthcare quality experts. Face validity was established through feedback from healthcare professionals. Then, the Amharic SAQ (SAQ-A) was distributed to 648 participants working in 11 public hospitals, and a total of 611 valid questionnaires were completed and returned (95.2% response rate). Cronbach’s alpha, McDonald’s omega, composite reliability, correlation analysis, and average variance estimation were calculated, and confirmatory factor analysis was performed. Descriptive analyses were performed to describe socio-demographic characteristics. A P-value of ≤0.05 was considered statistically significant. Tables, figures, charts, and texts are used for data presentation.

Result

The overall internal consistency (Cronbach’s alpha) for the 31-item SAQ-A was 0.903, indicating excellent reliability. Confirmatory factor analyses demonstrated a good model fit for each dimension and the entire construct (χ2=1086.675, df=412, p<0.001, comparative fit index (CFI)=0.923, Tucker Lewis index (TLI)=0.913, and root mean square error of approximation (RMSEA)=0.052). The positive response rate of healthcare workers in hospitals was 32.1%. The positive response rates of the six dimensions were teamwork climate (59.7%), safety climate (41.9%), job satisfaction (57.1%), working conditions (37.5%), perception of management (37.6%), and stress recognition (46.2%).

Conclusion

The Amharic translation of the SAQ showed good psychometric properties, making it a valuable tool for assessing safety attitudes among Amharic-speaking Ethiopian healthcare practitioners.
Single-cell RNA sequencing integrated with bulk RNA sequencing analysis identifies a tumor immune microenvironment-related lncRNA signature in lung adenocarcinoma
Authors: Ren Yuqing , Wu Ruhao , Li Chunwei , Liu Long , Li Lifeng , Weng Siyuan , Xu Hui , Xing Zhe , Zhang Yuyuan , Wang Libo , Liu Zaoqu , Han Xinwei
Published: March 2024

Background

Recently, long non-coding RNAs (lncRNAs) have been demonstrated as essential roles in tumor immune microenvironments (TIME). Nevertheless, researches on the clinical significance of TIME-related lncRNAs are limited in lung adenocarcinoma (LUAD).

Methods

Single-cell RNA sequencing and bulk RNA sequencing data are integrated to identify TIME-related lncRNAs. A total of 1368 LUAD patients are enrolled from 6 independent datasets. An integrative machine learning framework is introduced to develop a TIME-related lncRNA signature (TRLS).

Results

This study identified TIME-related lncRNAs from integrated analysis of single‑cell and bulk RNA sequencing data. According to these lncRNAs, a TIME-related lncRNA signature was developed and validated from an integrative procedure in six independent cohorts. TRLS exhibited a robust and reliable performance in predicting overall survival. Superior prediction performance barged TRLS to the forefront from comparison with general clinical features, molecular characters, and published signatures. Moreover, patients with low TRLS displayed abundant immune cell infiltration and active lipid metabolism, while patients with high TRLS harbored significant genomic alterations, high PD-L1 expression, and elevated DNA damage repair (DDR) relevance. Notably, subclass mapping analysis of nine immunotherapeutic cohorts demonstrated that patients with high TRLS were more sensitive to immunotherapy.

Conclusions

This study developed a promising tool based on TIME-related lncRNAs, which might contribute to tailored treatment and prognosis management of LUAD patients.
Regional disparities and risk factors of mortality among patients at high risk of sudden cardiac death in emerging countries: a nonrandomized controlled trial
Authors: Zhao Shuang , Ching Chi-Keong , Huang Dejia , Liu Yen-Bin , Rodriguez-Guerrero Diego A. , Hussin Azlan , Kim Young-Hoon , Van Dorn Brian , Zhou Xiaohong , Singh Balbir , Zhang Shu ,   the Improve SCA Investigators
Published: March 2024

Background

Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries.

Methods

Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD.

Results

We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531–0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116–0.343, p < 0.0001) lower SCD risk.

Conclusions

There was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent.

Trial registration

ClinicalTrials.gov, NCT02099721.
The effect of COVID-19 on malaria cases in Zambia: a mixed effect multilevel analysis
Authors: Sampa Mutale , Fisa Ronald , Mukuma Chilombo , Mwanza Mercy , Hamainza Busiku , Musonda Patrick
Published: March 2024

Background

The burden of Malaria in Zambia remains a challenge, with the entire population at risk of contracting this infectious disease. Despite concerted efforts by African countries, including Zambia, to implement malaria policies and strategies aimed at reducing case incidence, the region faces significant hurdles, especially with emerging pandemics such as COVID-19. The efforts to control malaria were impacted by the constraints imposed to curb its transmission during the COVID-19 pandemic. The aim of the study was to assess the effect of the COVID-19 pandemic on malaria cases in Zambia and the factors associated by comparing the COVID-19 period and the pre-COVID-19 era.

Methods

This was a cross-sectional panel study in which routinely collected programmatic data on malaria was used. The data were extracted from the Health Management Information System (HMIS) for the period January 2018 to January 2022. The period 2018 to 2022 was selected purely due to the availability of data and to avoid the problem of extrapolating too far away from the period of interest of the study. A summary of descriptive statistics was performed in which the number of cases were stratified by province, age group, and malaria cases. The association of these variables with the COVID-19 era was checked using the Wilcoxon rank-sum test and Kruskal‒Wallis test as applicable. In establishing the factors associated with the number of malaria cases, a mixed-effect multilevel model using the Poisson random intercept and random slope of the COVID-19 panel. The model was employed to deal with the possible correlation of the number of cases in the non-COVID-19 panel and the expected correlation of the number of cases in the COVID-19 panel.

Results

A total of 18,216 records were extracted from HMIS from January 2018 to January 2022. Stratifying this by the COVID-19 period/era, it was established that 8,852 malaria cases were recorded in the non-COVID-19 period, whereas 9,364 cases were recorded in the COVID-19 era. Most of the people with malaria were above the age of 15 years. Furthermore, the study found a significant increase in the relative incidence of the COVID-19 panel period compared to the non-COVID-19 panel period of 1.32, 95% CI (1.18, 1.48, p < 0.0001). The observed numbers, as well as the incident rate ratio, align with the hypothesis of this study, indicating an elevated incidence rate ratio of malaria during the COVID-19 period.

Conclusion

This study found that there was an increase in confirmed malaria cases during the COVID-19 period compared to the non-COVID-19 period. The study also found Age, Province, and COVID-19 period to be significantly associated with malaria cases.
Ethnobotany of traditional cosmetics among the Oromo women in Madda Walabu District, Bale Zone, Southeastern Ethiopia
Authors: Sultan Siraj , Telila Habte , Kumsa Lemessa
Published: March 2024

Traditional cosmetics play a significant role in the cultural practices and personal hygiene of many ethnic groups worldwide. The Oromo, an indigenous community in Ethiopia, has a rich history of utilizing local plants for cosmetic purposes. However, the use of plants as traditional cosmetics has only been poorly investigated as more emphasis was given to traditional medicines. The study thus aimed to identify and document plant species, and parts used in traditional cosmetics and associated knowledge, and practices among Oromo women in the Madda Walabu district, Southeastern Ethiopia. A total of 150 Oromo women were interviewed to gather ethnobotanical information including the plant species used for cosmetics, their preparation methods, and their applications. Ethnobotanical indices were computed to determine the most important species used by the women. A total of 48 plant species belonging to 31 families used as sources of traditional cosmetics were recorded. Most of these plants were trees. Leaves were the most commonly used plant part in traditional cosmetics, and maceration and decoction were the most common preparation methods applied to prepare traditional cosmetics. Topical application of traditional cosmetics was the most common, while oral infusions were rarely reported type of administration. All categories had high informant consensus factor (ICF) values, ranging from 0.80 to 0.98. The highest ICF value was found for skin treatment, followed by the hair, and face mask. Overall, Commiphora habessinica, Gnidia stenophylla, Kalanchoe lanceolata, Mimusops kummel, Sesamothamnus rivae, Terminalia brownii, T. laxiflora, Acacia drepanolobium, A. mellifera, and Aloe citrina were the most frequently cited and culturally important plants by Oromo women for traditional cosmetics in the area. The study highlights the importance of local plant resources for maintaining cultural practices and personal hygiene. However, the cultural heritage associated with traditional cosmetics is facing threats from various factors. Therefore, a continuous effort to document and disseminate knowledge about traditional cosmetics practices to ensure their preservation and transmission and awakening younger generations about the importance of traditional cosmetics and their role in cultural heritage is crucial.
Variation in traditional knowledge of culturally important macromycete species among three indigenous communities of Oaxaca, Mexico
Authors: López-García Alexanders , Gómez-Hernández Marko , Gándara Etelvina
Published: March 2024

Background

For centuries, wild mushrooms have been a forest resource of significant cultural value in several ethnic groups worldwide. In Mexico, extensive traditional knowledge on the use of fungal resources has been developed and deeply rooted. Mexico is the second country in the world in which the most species of wild mushroom are consumed, and it is considered a pioneer in ethnomycology. Nonetheless, there are still many indigenous groups in this country that have not been studied from an ethnomycological approach. The present study aimed to record the traditional knowledge on wild mushrooms in three indigenous groups of the state of Oaxaca, Mexico, and assess the variation in this knowledge within and across the studied groups.

Methods

The data were recorded from April to October 2022 within three communities belonging to the indigenous groups Chatino, Chontal, and Chinanteco. Through 84 interviews, information related to their knowledge of wild mushrooms was obtained. The cultural significance index of wild edible mushrooms was calculated for each community. Regression analyses, analysis of variance and covariance, t test, and non-metric multidimensional scaling analysis were performed to assess the distribution of traditional knowledge in the communities.

Results

A total of 32 culturally important mushroom species were recorded for the three indigenous groups (30 edible, 2 medicinal); 23 used by Chatinos, 16 by Chontales, and 6 by Chinantecos. Only Chatinos and Chinantecos use wild mushrooms in medicine. The cultural significance of wild edible mushrooms differed among groups. Traditional knowledge about wild mushrooms declines when the level of schooling increases and age decreases, especially in the Chatino group. This knowledge distributes more homogeneously in the Chontal and Chinanteco groups. Their age determines the difference in knowledge between men and women.

Conclusion

Documenting how traditional knowledge differs among ethnic groups is relevant for preserving cultural and biological diversity. Factors such as level of schooling and age can affect traditional knowledge of wild mushrooms, but the effects of these factors vary within and across communities. Conducting studies encompassing a broader range of variables is of interest for a better understanding of the human–mushroom relationship.
What features of drug treatment programs help, or not, with access? a qualitative study of the perspectives of family members and community-based organization staff in Atlantic Canada
Authors: Mathias Holly , Jackson Lois A. , Buxton Jane A. , Dubé Anik , Kiepek Niki , Martin Fiona , Martin Paula
Published: March 2024

Background

Withdrawal management and opioid agonist treatment (OAT) programs help to reduce some of the harms experienced by people who use substances (PWUS). There is literature on how features of drug treatment programs (e.g., policies and practices) are helpful, or not helpful, to PWUS when seeking access to, or in, treatment. There is, however, relatively little literature based on the perspectives of family members/family of choice of PWUS and community-based organization staff within the context of Atlantic Canada. This paper explored the perspectives of these two groups on what was helpful, or not, about drug treatment programs in Atlantic Canada in terms of supporting access to, and retention in, treatment.

Methods

One-on-one qualitative telephone interviews were conducted in 2020 with the two groups. Interviews focused on government-funded withdrawal management and OAT programs. Data were coded using a qualitative data management program (ATLAS.ti) and analyzed inductively for key themes/subthemes using grounded theory techniques.

Results

Fifteen family members/family of choice and 16 community-based organization staff members participated (n = 31). Participants spoke about features of drug treatment programs in various places, and noted features that were perceived as helpful (e.g., quick access), as well as not helpful (e.g., wait times, programs located far from where PWUS live). Some participants provided their perceptions of how PWUS felt when seeking or accessing treatment. A number of participants reported taking various actions to help support access to treatment, including providing transportation to programs. A few participants also provided suggestions for change to help support access and retention such as better alignment of mental health and addiction systems.

Conclusions

Participants highlighted several helpful and not helpful features of drug treatment programs in terms of supporting treatment access and retention. Previous studies with PWUS and in other places have reported similar features, some of which (e.g., wait times) have been reported for many years. Changes are needed to reduce barriers to access and retention including the changes recommended by study participants. It is critical that the voices of key groups, (including PWUS) are heard to ensure treatment programs in all places support access and retention.
Total iridoid glycoside extract of Lamiophlomis rotata (Benth) Kudo accelerates diabetic wound healing by the NRF2/COX2 axis
Authors: Geng Xiaoyu , Wang Ying , Li Huan , Song Liang , Luo Chen , Gu Xiaojie , Zhong Haixin , Chen Huilin , Chen Xinzhu , Wang Jianwei , Pan Zheng
Published: March 2024

Background

Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid glycosides are naturally occurring active compounds that can be used as the oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound healing and its associated mechanism is largely unclear.

Materials and methods

With macrophages and dermal fibroblasts in vitro, as well as a thickness excision model of db/db mouse in vivo, the role of IGLR in diabetic wound
healing and the probable mechanism of the action were investigated.

Results

Our results showed that IGLR suppressed oxidative distress and inflammation partly through the NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro. The intercellular communication between macrophages and dermal fibroblasts was investigated by the conditioned medium (CM) of IGLR treatment cells. The CM increased the transcription and translation of collagen I (COL1A1) and alpha smooth muscle actin (α-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory targets of the axis, like interleukin-1beta (IL-1β), interleukin 6 (IL-6), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In addition, the deposition of COL1A1, and the level of α-SMA, and Transforming growth factor-β1 (TGF-β1) obviously elevated, whereas that of pro-inflammatory factors reduced in the diabetic wound tissue with IGLR treatment.

Conclusion

IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 axis, thus promoting paracrine and accelerating wound healing in diabetes mice.

Graphical Abstract
Family case of Potocki-Lupski syndrome
Authors: Kolbasin L. N. , Dubrovskaya T. A. , Salnikova G. B. , Solovieva E. N. , Donnikov M. Yu. , Illarionov R. A. , Glotov A. S. , Kovalenko L. V. , Belotserkovtseva L. D.
Published: March 2024

Background

Potocki-Lupski syndrome (PTLS, OMIM # 610883) is a rare genetic developmental disorder resulting from a partial heterozygous microduplication at chromosome 17p11.2. The condition is characterized by a wide variability of clinical expression, which can make its clinical and molecular diagnosis challenging.

Case presentation

We report here a family (mother and her two children) diagnosed with PTLS. When examining children, neurological and psychological (neuropsychiatric) manifestations (speech delay, mild mental retardation), motor disorders, craniofacial dysmorphism (microcephaly, dolichocephaly, triangular face, wide bulging forehead, long chin, antimongoloid slant, "elfin" ears) were revealed. The suspected clinical diagnosis was confirmed by MLPA and CMA molecular genetic testing which revealed the presence of a segmental aneusomy; microduplication in the 17p11.2 region.

Conclusions

Children with PTLS can have a clinically recognizable and specific phenotype: craniofacial dysmorphism, motor and neurological manifestations, which may implicate a possible genetic disease to the attending physician. Moreover, each child with this syndrome is unique and may have a different clinical picture. The management of such patients requires a multidisciplinary team approach, including medical genetic counseling.
Peers plus mobile app for treatment in HIV (PATH): protocol for a randomized controlled trial to test a community-based integrated peer support and mHealth intervention to improve viral suppression among Hispanic and Black people living with HIV
Authors: Pitpitan Eileen V. , Horvath Keith J. , Aldous Jeannette , Stockman Jamila K. , Patterson Thomas L. , Liang Megan , Barrozo Constantino , Moore Veronica , Penninga Katherine , Smith Laramie R.
Published: March 2024

Background

Significant disparities continue to exist in the HIV care continuum, whereby Hispanic and Black people living with HIV (PLWH) are less likely to achieve viral suppression compared to their White counterparts. Studies have shown that intervention approaches that involve peer navigation may play an important role in supporting patients to stay engaged in HIV care. However, implementation may be challenging in real-world settings where there are limited resources to support peer navigators. Combining a peer navigation approach with scalable mobile health (mHealth) technology may improve impact and implementation outcomes.

Methods

We combined a peer navigation intervention with a mHealth application and are conducting a randomized controlled trial (RCT) to test the efficacy of this integrated “Peers plus mobile App for Treatment in HIV” (PATH) intervention to improve HIV care engagement, and ultimately sustained viral suppression, among Hispanic and Black PLWH. We will enroll up to 375 PLWH into a two-arm prospective RCT, conducting follow-up assessments every 3 months up to 12 months post-baseline. Participants randomized to the control arm will continue to receive usual care Ryan White Program case management services. Individuals randomized to receive the PATH intervention will receive usual care plus access to two main intervention components: (1) a peer navigation program and (2) a mHealth web application. The primary outcome is sustained HIV viral suppression (undetectable viral load observed at 6- and 12-month follow-up). Secondary outcomes are retention in HIV care, gaps in HIV medical visits, and self-reported ART adherence. Recruitment for the RCT began in November 2021 and will continue until June 2024. Follow-up assessments and medical chart abstractions will be conducted to collect measurements of outcome variables.

Discussion

The efficacy trial of PATH will help to fill gaps in our scientific understanding of how a combined peer navigation and mHealth approach may produce effects on HIV care outcomes while addressing potential implementation challenges of peer navigation in Ryan White-funded clinics.

Trial registration

The PATH trial is registered at the United States National Institutes of Health National Library of Medicine (ClinicalTrials.gov) under ID # NCT05427318. Registered on 22 June 2022.
Evaluation of endometrial receptivity in women with unexplained infertility by shear wave elastography
Authors: Li Zheng-ying , Cai Lu , Zhang Zhi-jun , Zou Hai-rong , He Mei , Qin Mei-lin , Wang Hui
Published: March 2024

Objectives

The endometrium of most unexplained infertility (UI) patients has been altered histologically. Shear wave elastography (SWE) is utilized to assess the signature of living tissue. This study aimed to explore the value of SWE in evaluating endometrial receptivity (ER) in UI patients.

Methods

In total, 59 UI patients (UI group) and 52 normal control women (NC group) who received fertility consultation in our hospital were included between January 2022 and June 2023. We divided them into the late-proliferative phase of UI group (LPUI; n = 59), mid-secretory phase of UI group (MPUI; n = 41), late-proliferative phase of NC group (LPNC; n = 52), and mid-secretory phase of NC group (MPNC; n = 45). Transvaginal ultrasonography and SWE were performed during the LP and MP. Endometrial thickness (EMT), uterine artery pulsatility index (UA-PI), endometrial mean elasticity (E-mean), and mean shear wave velocities (SWV-mean) were measured.

Results

There were significant differences in E-mean, SWV-mean, EMT, and UA-PI between the UI group and the NC group during both the LP and MP (p MPNC vs MPUI < 0.05, p LPNC vs LPUI < 0.05). E-mean and SWV-mean decreased with increasing EMT but increased with increasing UA-PI (p < 0.05). The most effective parameter for evaluating ER in UI patients is the E-mean (AUC = 0.89).

Conclusions

UI patients exhibited thinner endometrium, increased endometrial stiffness, and poor endometrial blood perfusion. E-mean was the most effective parameter to evaluate ER in UI patients. The study preliminarily proved that SWE is a promising non-invasive tool for evaluating the condition of endometrium.

Critical relevance statement

This study aimed to explore the significance of endometrial elasticity measured by SWE in evaluating patients with UI. The findings revealed a correlation between EMT, UA-PI, and E-mean. Endometrial elasticity can serve as an effective indicator for predicting ER.

Key points

1. To explore the significance of endometrial elasticity in assessing patients with UI.

2. The endometrium of UI patient exhibited thinness, stiffness, and poor blood perfusion.

3. Endometrial elasticity serves as a valuable indicator for evaluating endometrial receptivity.

Graphical Abstract
Semi-automated computer vision-based tracking of multiple industrial entities: a framework and dataset creation approach
Authors: Rutinowski Jérôme , Youssef Hazem , Franke Sven , Priyanta Irfan Fachrudin , Polachowski Frederik , Roidl Moritz , Reining Christopher
Published: March 2024

This contribution presents the TOMIE framework (Tracking Of Multiple Industrial Entities), a framework for the continuous tracking of industrial entities (e.g., pallets, crates, barrels) over a network of, in this example, six RGB cameras. This framework makes use of multiple sensors, data pipelines, and data annotation procedures, and is described in detail in this contribution. With the vision of a fully automated tracking system for industrial entities in mind, it enables researchers to efficiently capture high-quality data in an industrial setting. Using this framework, an image dataset, the TOMIE dataset, is created, which at the same time is used to gauge the framework’s validity. This dataset contains annotation files for 112,860 frames and 640,936 entity instances that are captured from a set of six cameras that perceive a large indoor space. This dataset out-scales comparable datasets by a factor of four and is made up of scenarios, drawn from industrial applications from the sector of warehousing. Three tracking algorithms, namely ByteTrack, Bot-Sort, and SiamMOT, are applied to this dataset, serving as a proof-of-concept and providing tracking results that are comparable to the state of the art.
Co-Processed Crystalline Solids of Ivermectin with Span® 60 as Solubility Enhancers of Ivermectin in Natural Oils
Authors: de Vos Luandri , Gerber Minja , Liebenberg Wilna , Wessels Johanna C. , Lemmer Hendrik J. R.
Published: March 2024

Despite being discovered over five decades ago, little is still known about ivermectin. Ivermectin has several physico-chemical properties that can result in it having poor bioavailability. In this study, polymorphic and co-crystal screening was used to see if such solid-state modifications can improve the oil solubility of ivermectin. Span® 60, a lipophilic non-ionic surfactant, was chosen as co-former. The rationale behind attempting to improve oil solubility was to use ivermectin in future topical and transdermal preparations to treat a range of skin conditions like scabies and head lice. Physical mixtures were also prepared in the same molar ratios as the co-crystal candidates, to serve as controls. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The FTIR spectra of the co-crystal candidates showed the presence of Span® 60’s alkyl chain peaks, which were absent in the spectra of the physical mixtures. Due to the absence of single-crystal X-ray data, co-crystal formation could not be confirmed, and therefore these co-crystal candidates were referred to as co-processed crystalline solids. Following characterization, the solid-state forms, physical mixtures and ivermectin raw material were dissolved in natural penetration enhancers, i.e., avocado oil (AVO) and evening primrose oil (EPO). The co-processed solids showed increased oil solubility by up to 169% compared to ivermectin raw material. The results suggest that co-processing of ivermectin with Span® 60 can be used to increase its oil solubility and can be useful in the development of oil-based drug formulations.

Graphical Abstract