bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance in Kahoot! activities as predictive of exam performance
Authors: Garza MC , Olivan S , Monleón E , Cisneros Ana Isabel , García-Barrios A , Ochoa I , Whyte J , Lamiquiz-Moneo I
Published: June 2023

Background

Game-based learning (GBL) is effective for increasing participation, creativity, and student motivation. However, the discriminative value of GBL for knowledge acquisition has not yet been proven. The aim of this study is to assess the value of Kahoot! as a discriminative tool for formative assessment in medical education in two different subjects.

Methods

A prospective experimental study was conducted on a sample of 173 students enrolled in neuroanatomy (2021–2022). One hundred twenty-five students individually completed the Kahoot! prior to the final exam. In addition, students enrolled in human histology during two academic courses were included in the study. The control group course (2018–2019) received a traditional teaching methodology (N = 211), while Kahoot! was implemented during 2020–2021 (N = 200). All students completed similar final exams for neuroanatomy and human histology based on theory tests and image exams.

Results

The correlation between the Kahoot score and the final grade was analyzed for all students enrolled in neuroanatomy who completed both exercises. The correlation between the Kahoot exercise and the theory test, image exam and final grade was significantly positive in all cases (r = 0.334 p < 0.001, r = 0.278 p = 0.002 and r = 0.355 p < 0.001, respectively). Moreover, students who completed the Kahoot! exercise obtained significantly higher grades in all parts of the exam. Regarding human histology, the theory tests, image exams and final grades were significantly higher when using Kahoot! versus the “traditional” methodology (p < 0.001, p < 0.001 and p = 0.014, respectively).

Conclusions

Our study demonstrates for the first time that Kahoot! can be used to improve and predict the final grade in medical education subjects.
The Sapria himalayana genome provides new insights into the lifestyle of endoparasitic plants
Authors: Guo Xuelian , Hu Xiaodi , Li Jianwu , Shao Bingyi , Wang Yajun , Wang Long , Li Kui , Lin Dongliang , Wang Hanchen , Gao Zhiyuan , Jiao Yuannian , Wen Yingying , Ji Hongyu , Ma Chongbo , Ge Song , Jiang Wenkai , Jin Xiaohua
Published: June 2023

Background

Sapria himalayana (Rafflesiaceae) is an endoparasitic plant characterized by a greatly reduced vegetative body and giant flowers; however, the mechanisms underlying its special lifestyle and greatly altered plant form remain unknown. To illustrate the evolution and adaptation of S. himalayasna, we report its de novo assembled genome and key insights into the molecular basis of its floral development, flowering time, fatty acid biosynthesis, and defense responses.

Results

The genome of S. himalayana is ~ 1.92 Gb with 13,670 protein-coding genes, indicating remarkable gene loss (~ 54%), especially genes involved in photosynthesis, plant body, nutrients, and defense response. Genes specifying floral organ identity and controlling organ size were identified in S. himalayana and Rafflesia cantleyi, and showed analogous spatiotemporal expression patterns in both plant species. Although the plastid genome had been lost, plastids likely biosynthesize essential fatty acids and amino acids (aromatic amino acids and lysine). A set of credible and functional horizontal gene transfer (HGT) events (involving genes and mRNAs) were identified in the nuclear and mitochondrial genomes of S. himalayana, most of which were under purifying selection. Convergent HGTs in Cuscuta, Orobanchaceae, and S. himalayana were mainly expressed at the parasite–host interface. Together, these results suggest that HGTs act as a bridge between the parasite and host, assisting the parasite in acquiring nutrients from the host.

Conclusions

Our results provide new insights into the flower development process and endoparasitic lifestyle of Rafflesiaceae plants. The amount of gene loss in S. himalayana is consistent with the degree of reduction in its body plan. HGT events are common among endoparasites and play an important role in their lifestyle adaptation.
Snakes on a plain: biotic and abiotic factors determine venom compositional variation in a wide-ranging generalist rattlesnake
Authors: Smith Cara F. , Nikolakis Zachary L. , Ivey Kathleen , Perry Blair W. , Schield Drew R. , Balchan Neil R. , Parker Joshua , Hansen Kirk C. , Saviola Anthony J. , Castoe Todd A. , Mackessy Stephen P.
Published: June 2023

Background

Snake venoms are trophic adaptations that represent an ideal model to examine the evolutionary factors that shape polymorphic traits under strong natural selection. Venom compositional variation is substantial within and among venomous snake species. However, the forces shaping this phenotypic complexity, as well as the potential integrated roles of biotic and abiotic factors, have received little attention. Here, we investigate geographic variation in venom composition in a wide-ranging rattlesnake (Crotalus viridis viridis) and contextualize this variation by investigating dietary, phylogenetic, and environmental variables that covary with venom.

Results

Using shotgun proteomics, venom biochemical profiling, and lethality assays, we identify 2 distinct divergent phenotypes that characterize major axes of venom variation in this species: a myotoxin-rich phenotype and a snake venom metalloprotease (SVMP)-rich phenotype. We find that dietary availability and temperature-related abiotic factors are correlated with geographic trends in venom composition.

Conclusions

Our findings highlight the potential for snake venoms to vary extensively within species, for this variation to be driven by biotic and abiotic factors, and for the importance of integrating biotic and abiotic variation for understanding complex trait evolution. Links between venom variation and variation in biotic and abiotic factors indicate that venom variation likely results from substantial geographic variation in selection regimes that determine the efficacy of venom phenotypes across populations and snake species. Our results highlight the cascading influence of abiotic factors on biotic factors that ultimately shape venom phenotype, providing evidence for a central role of local selection as a key driver of venom variation.
Contrasting outcomes of genome reduction in mikrocytids and microsporidians
Authors: Žárský Vojtečh , Karnkowska Anna , Boscaro Vittorio , Trznadel Morelia , Whelan Thomas A. , Hiltunen-Thorén Markus , Onut-Brännström Ioana , Abbott Cathryn L. , Fast Naomi M. , Burki Fabien , Keeling Patrick J.
Published: June 2023

Background

Intracellular symbionts often undergo genome reduction, losing both coding and non-coding DNA in a process that ultimately produces small, gene-dense genomes with few genes. Among eukaryotes, an extreme example is found in microsporidians, which are anaerobic, obligate intracellular parasites related to fungi that have the smallest nuclear genomes known (except for the relic nucleomorphs of some secondary plastids). Mikrocytids are superficially similar to microsporidians: they are also small, reduced, obligate parasites; however, as they belong to a very different branch of the tree of eukaryotes, the rhizarians, such similarities must have evolved in parallel. Since little genomic data are available from mikrocytids, we assembled a draft genome of the type species, Mikrocytos mackini, and compared the genomic architecture and content of microsporidians and mikrocytids to identify common characteristics of reduction and possible convergent evolution.

Results

At the coarsest level, the genome of M. mackini does not exhibit signs of extreme genome reduction; at 49.7 Mbp with 14,372 genes, the assembly is much larger and gene-rich than those of microsporidians. However, much of the genomic sequence and most (8075) of the protein-coding genes code for transposons, and may not contribute much of functional relevance to the parasite. Indeed, the energy and carbon metabolism of M. mackini share several similarities with those of microsporidians. Overall, the predicted proteome involved in cellular functions is quite reduced and gene sequences are extremely divergent. Microsporidians and mikrocytids also share highly reduced spliceosomes that have retained a strikingly similar subset of proteins despite having reduced independently. In contrast, the spliceosomal introns in mikrocytids are very different from those of microsporidians in that they are numerous, conserved in sequence, and constrained to an exceptionally narrow size range (all 16 or 17 nucleotides long) at the shortest extreme of known intron lengths.

Conclusions

Nuclear genome reduction has taken place many times and has proceeded along different routes in different lineages. Mikrocytids show a mix of similarities and differences with other extreme cases, including uncoupling the actual size of a genome with its functional reduction.
Predicting the risk of malaria re-introduction in countries certified malaria-free: a systematic review
Authors: Lu Guangyu , Zhang Dongying , Chen Juan , Cao Yuanyuan , Chai Liying , Liu Kaixuan , Chong Zeying , Zhang Yuying , Lu Yan , Heuschen Anna-Katharina , Müller Olaf , Zhu Guoding , Cao Jun
Published: June 2023

Background

Predicting the risk of malaria in countries certified malaria-free is crucial for the prevention of re-introduction. This review aimed to identify and describe existing prediction models for malaria re-introduction risk in eliminated settings.

Methods

A systematic literature search following the PRISMA guidelines was carried out. Studies that developed or validated a malaria risk prediction model in eliminated settings were included. At least two authors independently extracted data using a pre-defined checklist developed by experts in the field. The risk of bias was assessed using both the prediction model risk of bias assessment tool (PROBAST) and the adapted Newcastle–Ottawa Scale (aNOS).

Results

A total 10,075 references were screened and 10 articles describing 11 malaria re-introduction risk prediction models in 6 countries certified malaria free. Three-fifths of the included prediction models were developed for the European region. Identified parameters predicting malaria re-introduction risk included environmental and meteorological, vectorial, population migration, and surveillance and response related factors. Substantial heterogeneity in predictors was observed among the models. All studies were rated at a high risk of bias by PROBAST, mostly because of a lack of internal and external validation of the models. Some studies were rated at a low risk of bias by the aNOS scale.

Conclusions

Malaria re-introduction risk remains substantial in many countries that have eliminated malaria. Multiple factors were identified which could predict malaria risk in eliminated settings. Although the population movement is well acknowledged as a risk factor associated with the malaria re-introduction risk in eliminated settings, it is not frequently incorporated in the risk prediction models. This review indicated that the proposed models were generally poorly validated. Therefore, future emphasis should be first placed on the validation of existing models.
Accessing hepatitis C direct acting antivirals among people living with hepatitis C: a qualitative study
Authors: Antoniou Tony , Pritlove Cheryl , Shearer Dana , Tadrous Mina , Shah Hemant , Gomes Tara
Published: June 2023

Background

Hepatitis C is curable with direct-acting antivirals (DAAs). However, treatment uptake remains low among marginalized populations such as people who inject drugs. We sought to understand challenges to treatment uptake with DAAs among people living with hepatitis C and compare treatment experiences between people who do and do not inject prescription and/or unregulated drugs.

Methods

We conducted a qualitative study using focus groups with 23 adults aged 18 years and over who completed DAA treatment or were about to begin such treatment at the time of the study. Participants were recruited from hepatitis C treatment clinics across Toronto, Ontario. We drew upon stigma theory to interpret participants’ accounts.

Results

Following analysis and interpretation, we generated five theoretically-informed themes characterizing the experiences of individuals accessing DAAs: “being ‘worthy’ of the cure”, “spatially enacted stigma”, “countering social and structural vulnerability: the importance of peers”, “identity disruption and contagion: attaining a ‘social cure’” and “challenging stigma with population-based screening”. Overall, our findings suggest that structural stigma generated and reproduced through healthcare encounters limits access to DAAs among people who inject drugs. Peer-based programs and population-based screening were proposed by participants as mechanisms for countering stigma within health care settings and ‘normalizing’ hepatitis C among the general population.

Conclusions

Despite the availability of curative therapies, access to such treatment for people who inject drugs is limited by stigma enacted in and structured within healthcare encounters. Developing novel, low-threshold delivery programs that remove power differentials and attend to the social and structural determinants of health and reinfection are needed to facilitate further scale up of DAAs and support the goal of eradicating hepatitis C as a public health threat.
Yunnan Baiyao-loaded multifunctional microneedle patches for rapid hemostasis and cutaneous wound healing
Authors: Yang Jie , Wang Xiaocheng , Wu Dan , Yi Kexin , Zhao Yuanjin
Published: June 2023

Microneedle patches have been extensively employed for wound healing, while the lack of rapid hemostasis efficiency and multiple tissue-repair properties restrict their values in hemorrhagic wound applications. Herein, we propose a Yunnan Baiyao-loaded multifunctional microneedle patch, namely (BY + EGF)@MN, with deep tissue penetration, hemostasis efficiency and regenerative properties for hemorrhagic wound healing. The (BY + EGF)@MNs are designed with a BY-loaded Bletilla striata polysaccharide (BSP) base for rapid hemostasis and epidermal growth factor (EGF)-loaded GelMA tips for subsequent wound healing. As the BSP base can be fastly dissolved and completely release BY in 6 min to promote platelet adhesion and activate coagulation system, while the EGF can achieve a controlled and sustained release behavior in 7 days with the gradual degradation of the GelMA tips, the (BY + EGF)@MNs exhibit strong pro-coagulability and satisfactory hemostatic effect in a rat hepatic hemorrhage wound model. Based on the multifunctional characteristics, we have verified that when applied in rat cutaneous wounds, the proposed MNs can accelerate the wound healing process by enhancing neovascularization, fibroblast density, and collagen deposition. Thus, we believe that such (BY + EGF)@MNs are promising candidates for rapid hemostasis and diverse wound healing applications.

Graphical Abstract
WHODAS measurement properties for women with dysmenorrhea
Authors: de Arruda Guilherme Tavares , de Melo Mantovan Sara Giovanna , Da Roza Thuane , Silva Barbara Inácio da , Tonon da Luz Soraia Cristina , Avila Mariana Arias
Published: June 2023

Background

There is an association of dysmenorrhea with human functioning and disability. However, no patient-reported outcome measure has been developed to assess this construct in women with dysmenorrhea. WHODAS 2.0 has been recognized as an important generic patient-reported outcome information of physical function and disability. Thus, the aim of this study was to assess the measurement properties of the WHODAS 2.0 in women with dysmenorrhea.

Methods

This is an online and cross-sectional study conducted with Brazilian women aged 14 to 42 years with self-report of dysmenorrhea in the last three months. According to COSMIN, structural validity was evaluated by exploratory and confirmatory factor analysis; internal consistency by Cronbach’s Alpha; measurement invariance by multigroup confirmatory factor analysis between geographic regions of Brazil; and construct validity by correlating WHODAS 2.0 to the Numerical Rating Scale for pain severity.

Results

One thousand three hundred and eighty-seven women (24.7 ± 6.5 years) with dysmenorrhea participated in the study. WHODAS 2.0 presented a single factor by exploratory factor analysis and adequate model by confirmatory factor analysis (CFI = 0.924, TLI = 0.900, RMSEA = 0.038), excellent internal consistence (α = 0.892) for all items and an invariancy across geographic regions (ΔCFI ≤ 0.01 and ΔRMSEA < 0.015). Correlation between WHODAS 2.0 and numerical rating scale was positive and moderate (r = 0.337).

Conclusion

WHODAS 2.0 has a valid structure to assess functioning and disability related to dysmenorrhea in women.
Embedding rapid reviews in health policy and systems decision-making: Impacts and lessons learned from four low- and middle-income countries
Authors: Robson Reid C. , Thomas Sonia M. , Langlois Étienne V. , Mijumbi Rhona , Kawooya Ismael , Antony Jesmin , Courvoisier Melissa , Amog Krystle , Marten Robert , Chikovani Ivdity , Nambiar Devaki , Ved Rajani R. , Bhaumik Soumyadeep , Balqis-Ali Nur Zahirah , Sararaks Sondi , Md. Sharif Shakirah , Kangwende Rugare Abigail , Munatsi Ronald , Straus Sharon E. , Tricco Andrea C.
Published: June 2023

Background

Demand for rapid evidence-based syntheses to inform health policy and systems decision-making has increased worldwide, including in low- and middle-income countries (LMICs). To promote use of rapid syntheses in LMICs, the WHO’s Alliance for Health Policy and Systems Research (AHPSR) created the Embedding Rapid Reviews in Health Systems Decision-Making (ERA) Initiative. Following a call for proposals, four LMICs were selected (Georgia, India, Malaysia and Zimbabwe) and supported for 1 year to embed rapid response platforms within a public institution with a health policy or systems decision-making mandate.

Methods

While the selected platforms had experience in health policy and systems research and evidence syntheses, platforms were less confident conducting rapid evidence syntheses. A technical assistance centre (TAC) was created from the outset to develop and lead a capacity-strengthening program for rapid syntheses, tailored to the platforms based on their original proposals and needs as assessed in a baseline questionnaire. The program included training in rapid synthesis methods, as well as generating synthesis demand, engaging knowledge users and ensuring knowledge uptake. Modalities included live training webinars, in-country workshops and support through phone, email and an online platform. LMICs provided regular updates on policy-makers’ requests and the rapid products provided, as well as barriers, facilitators and impacts. Post-initiative, platforms were surveyed.

Results

Platforms provided rapid syntheses across a range of AHPSR themes, and successfully engaged national- and state-level policy-makers. Examples of substantial policy impact were observed, including for COVID-19. Although the post-initiative survey response rate was low, three quarters of those responding felt confident in their ability to conduct a rapid evidence synthesis. Lessons learned coalesced around three themes – the importance of context-specific expertise in conducting reviews, facilitating cross-platform learning, and planning for platform sustainability.

Conclusions

The ERA initiative successfully established rapid response platforms in four LMICs. The short timeframe limited the number of rapid products produced, but there were examples of substantial impact and growing demand. We emphasize that LMICs can and should be involved not only in identifying and articulating needs but as co-designers in their own capacity-strengthening programs. More time is required to assess whether these platforms will be sustained for the long-term.
Cross-sectional and longitudinal associations of domain-specific physical activity composition with health-related quality of life in childhood and adolescence in Australia
Authors: Kemp Byron J. , Dumuid Dorothea , Chong Kar Hau , Parrish Anne-Maree , Cliff Dylan
Published: June 2023

Background

Health benefits have been linked with physical activity (PA), as well as some domains of PA among youth (e.g. organized PA and active transport). However, less is known about whether some PA domains are more beneficial than others. There is also a lack of evidence about whether health outcomes are related to the composition of PA (i.e. the share of PA spent in different domains). This study aimed to identify: (1) how the absolute durations of organized PA, non-organized PA, active transport and active chores/work at 10-11y are individually associated with physical, psychosocial and total health-related quality of life (HRQOL) at 10-11y and 12-13y; and (2) how the domain-specific composition of PA at 10-11y is associated with HRQOL at 10-11y and 12-13y.

Methods

Data from the Longitudinal Study of Australian Children were used in cross-sectional (n ≥ 2730) and longitudinal analyses (n ≥ 2376). Measurement included the Pediatric Quality of Life Inventory (PedsQL™) for HRQOL domains and one-day time-use diaries (TUDs) for PA domains. Robust linear regression models were used, controlling for age, sex, pubertal status, socioeconomic position, body mass index and TUD context (season and school attendance). Compositional models additionally adjusted for total PA duration and longitudinal models controlled for baseline PedsQL™ scores.

Results

Non-compositional models indicated that the duration of organized PA, and to a lesser extent non-organized PA, were positively but weakly associated with some HRQOL outcomes at 10-11y. These trends were not reflected in longitudinal models, although a 30-min increase in non-organized PA per day did predict marginally better psychosocial HRQOL at 12-13y (+ 0.17%; 95%CI =  + 0.03%, + 0.32%). Compositional models revealed that a 30-min increase in organized PA relative to other domains was positively but weakly associated with physical (+ 0.32%; 95%CI =  + 0.01%, + 0.63%), psychosocial (+ 0.41%; 95%CI =  + 0.11%, + 0.72%) and total HRQOL (+ 0.39%; 95%CI =  + 0.12%, + 0.66%) at 10-11y. However, the overall PA composition at 10-11y was not related to HRQOL at 12-13y.

Conclusions

Non-compositional and compositional models generally concurred on the direction of cross-sectional and longitudinal relationships (and lack thereof) between PA domains and HRQOL outcomes. The strongest associations were cross-sectional between organized PA and HRQOL at 10-11y. However, all associations between PA domains and HRQOL outcomes were weak and may not be clinically meaningful.
University students’ fertility awareness and its influencing factors: a systematic review
Authors: Ren Yue , Xie Yue , Xu Qulian , Long Miaochen , Zheng Ying , Li Lin , Niu Changmin
Published: June 2023

Introduction

In recent years, a growing number of researchers have begun to study fertility awareness (FA). Evidence suggests that college students in their reproductive years have a common understanding of fertility, risk factors for infertility, and assisted reproductive technologies. Therefore, this systematic review summarizes these studies and explores the factors affecting college students’ fertility awareness.

Methods

A systematic literature search of databases (PUBMED/MEDLINE, Cochrane, Web of Science, Embase, and EBSCO) was conducted from inception to September 2022. Studies that assessed the levels of fertility awareness and factors influencing college students were considered for the review. The qualities of the included studies were evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. This systematic review is reported according to the preferred reporting items for systematic review (PRISMA) guidelines.

Results

Twenty-one articles met the eligibility criteria and were included. The preliminary results showed that participants reported low to moderate FA. Female medical students demonstrated higher levels of fertility awareness. The association between age, years of education, and FA was insufficient.

Conclusion

The results of the current study suggest that increased FA interventions are warranted, especially for the male, non-medical student population. Governments and educational institutions should strengthen education programs for young students on reproductive health to help them raise awareness about childbirth, and society should provide family support for young people.
Phylogenetic characterization of canine distemper virus from stray dogs in Kathmandu Valley
Authors: Manandhar Prajwol , Napit Rajindra , Pradhan Saman M , Rajbhandari Pragun G , Moravek Jessie A , Joshi Pranav R , Shrestha Rima D , Karmacharya Dibesh
Published: June 2023

Canine distemper is a highly contagious, often fatal disease caused by canine distemper virus (CDV) in domestic dogs and wild carnivores. The virus has caused mass epidemics in both wild and captive carnivores of high conservation value such as tigers, lions and leopards. Hence, understanding and managing CDV outbreaks is particularly important in Nepal, which is home to many species of threatened wild carnivores including tigers, leopards, snow leopards, dholes and wolves, and also contains a large population of stray dogs. Previous studies have suggested that CDV may pose a threat to wild carnivores, but there have not been any studies characterizing the genetic strains of the virus circulating in Nepal’s carnivores. We collected invasive and non-invasive biological samples from stray dogs in Kathmandu Valley and genetically characterized the strains of CDV in the dogs to belong to the Asia-5 lineage by using phylogenetic analysis. The same lineage also contained CDV strains sequenced from dogs, civets, red panda and lions in India. Based on our phylogenetic analysis, we think it is likely that CDV is maintained through sylvatic cycle among sympatric carnivores allowing the recurring spillovers and outbreaks. It is crucial to prevent the virus transmission from reservoir hosts to other species, especially threatened populations of large carnivores in Nepal. Hence, we recommend for regular surveillance of CDV targeting wild carnivores in addition to the domestic dogs.
The features of high-risk human papillomavirus infection in different female genital sites and impacts on HPV-based cervical cancer screening
Authors: Li Tingyuan , Chen Simiao , Li Xinyue , Wu Zeni , Zhao Yuqian , Cui Jianfeng , Liu Bin , Chen Feng , Zhang Xun , Qiao Youlin , Chen Wen
Published: June 2023

Background

The causal role of high-risk Human papillomavirus (HR-HPV) in the pathogenesis of anogenital cancers is well established. In contrast, information on HR-HPV distribution of continuous anatomic sites within the female genital tract is limited, and the impact of sample type on the clinical performance in HPV-based cervical cancer screening warrants investigation.

Methods

A total of 2,646 Chinese women were enrolled in the study from May 2006 to April 2007. We analyzed the infection features by infection status and pathological diagnoses of 489 women with complete HR-HPV type and viral load data on the cervix, upper vagina, lower vagina, and perineum samples. Additionally, we assessed the clinical performance for detecting high-grade cervical intraepithelial neoplasia of grade two or worse (≥ CIN2) among these four types of samples.

Results

HR-HPV positivity rate was lower in the cervix (51.53%) and perineum (55.83%), higher in the upper (65.64%) and lower vagina (64.42%), and increased with the severity of cervical histological lesions (all P<0.001). Single infection was more dominant than multiple infections at each anatomic site of the female genital tract. The proportion of single HR-HPV infection decreased successively from the cervix (67.05%) to the perineum (50.00%) (Ptrend=0.019) in cervical intraepithelial neoplasia grade 1 (CIN1) and was higher in samples of the cervix (85.11%) and perineum (72.34%) in ≥ CIN2. In addition, the highest viral load was observed in the cervix compared to the other three sites. The overall agreement of the cervical and perineum samples was 79.35% and increased continuously from normal (76.55%) to ≥ CIN2 (91.49%). As for the detection of ≥ CIN2, the sensitivity was 100.00%, 97.87%, 95.74%, and 91.49% for the cervix, upper vagina, lower vagina, and perineum samples, respectively.

Conclusions

Single HR-HPV infection predominated throughout the female genital tract, but the viral load was lower compared to multiple HR-HPV infections. Despite the decreasing viral load from cervix to perineum, the clinical performance for detecting ≥ CIN2 of the perineum sample was comparable to that of the cervix.
Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer
Authors: Wang Weikai , Lu Kaizhong , Jiang Xin , Wei Qi , Zhu Liyuan , Wang Xian , Jin Hongchuan , Feng Lifeng
Published: June 2023

Introduction

Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, the crosstalk between cuproptosis and ferroptosis is obscure.

Materials and methods

We analyzed the effect of ferroptosis inducers on copper ionophores-induced cell death through CCK-8 assay. Cuproptosis was studied using immunofluorescence and protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR and western blot were adopted to explore the machinery of ferroptosis inducers enhanced cuproptosis. And mouse xenograft model was built to detect the synergy effect of elesclomol-Cu and sorafenib in vivo.

Results

Herein we found that ferroptosis inducers sorafenib and erastin could enhance cuproptosis in primary liver cancer cells by increasing copper dependent lipoylated protein aggregation. Mechanically, sorafenib and erastin upregulated protein lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) protein degradation, and reduced intracellular copper chelator glutathione (GSH) synthesis through inhibiting cystine importing.

Discussion/Conclusion

Our findings proposed that combination of ferroptosis inducers and copper ionophores to co-targeting ferroptosis and cuproptosis could be a novel therapeutic strategy for primary liver cancer.
Do ethnic chinese older adults with epithelial ovarian cancer survive a poorer prognosis?
Authors: Huang Wu , Bao Yiting , Luo Xukai , Yao Liangqing , Yuan Lei
Published: June 2023

Background

The risk of suffering epithelial ovarian cancer (EOC) for women increases with age evidently, while the prognosis of older EOC patients remain unclear. Against the backdrop of the accelerate aging process in China, this paper investigates whether the older EOC patients have a lower overall survival probability than the younger patients based on the sample of ethnic Chinese population.

Methods

A total of 323 ethnic Chinese patients diagnosed as epithelial ovarian cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared the overall survival probability between the younger group (< 70 years) and the older patients group (≥ 70 years). Survival curves were drawn using the Kaplan-Meier method, comparisons among different subgroups were evaluated using log-rank tests, and independent prognostic factors were identified by univariate and multivariate Cox regression analyses.

Results

43 patients were (13.3%) in the older patients group and 280 (86.7%) in the younger group. The distribution patterns between two groups were significantly different with regard to marital status, histologic type and FIGO stage. The median overall survival (OS) was significantly longer in the younger group than the older patients group (not reached vs. median 39 months, p < 0.05). The multivariate analysis demonstrated that the age (The older vs. the younger, HR: 1.967, P = 0.007), primary tumor laterality (HR: 1.849, P = 0.009), and FIGO stage (III vs. I, HR: 3.588, P = 0.001; and IV vs. I, HR: 4.382, P = 0.001; respectively) remained as important risk factors while Histology (HGSOC vs. CCOC, HR: 0.479, P = 0.025; and LGSOC/MOC/EC vs. CCOC, HR: 0.390, P = 0.034; respectively) and the number of lymph node dissected more than 10 was a protective factor (HR: 0.397, P = 0.008). In an analysis of 104 pairs of patients matched on the basis of the propensity score, the older patients group had significantly lower overall mortality (HR = 2.561, P = 0.002).

Conclusion

Ethnic Chinese Older EOC patients have a worse prognosis than the younger patients.
Epiphany: predicting Hi-C contact maps from 1D epigenomic signals
Authors: Yang Rui , Das Arnav , Gao Vianne R. , Karbalayghareh Alireza , Noble William S. , Bilmes Jeffrey A. , Leslie Christina S.
Published: June 2023

Recent deep learning models that predict the Hi-C contact map from DNA sequence achieve promising accuracy but cannot generalize to new cell types and or even capture differences among training cell types. We propose Epiphany, a neural network to predict cell-type-specific Hi-C contact maps from widely available epigenomic tracks. Epiphany uses bidirectional long short-term memory layers to capture long-range dependencies and optionally a generative adversarial network architecture to encourage contact map realism. Epiphany shows excellent generalization to held-out chromosomes within and across cell types, yields accurate TAD and interaction calls, and predicts structural changes caused by perturbations of epigenomic signals.
Diagnostic challenges for Aelurostrongylus abstrusus infection in cats from endemic areas in Italy
Authors: Vismarra Alice , Schnyder Manuela , Strube Christina , Kramer Laura , Colombo Liliana , Genchi Marco
Published: June 2023

Background

The lungworm Aelurostrongylus abstrusus infects wild and domestic feline species worldwide and is considered a primary respiratory parasite of cats. Definitive diagnosis is based on the identification of first-stage larvae (L1s) released in faeces approximately 5 to 6 weeks after infection. More recently, serology has been shown to be a diagnostic alternative for A. abstrusus infection in cats. The present study aimed at evaluating the diagnostic performance of serological antibody detection compared to faecal examination for A. abstrusus infection in a population of cats with known infection status from endemic areas in Italy and to identify factors (larval scores, age, co-infections with other helminths) that may influence test sensitivity and specificity of serology.

Methods

All cats resulting positive using the Baermann technique (n = 78) were tested with the A. abstrusus ELISA. An additional 90 serum samples from cats living in three geographical areas with infection prevalence > 10%, but that resulted negative on Baermann, were also tested.

Results

Among 78 cats copromicroscopically positive for L1s of A. abstrusus (Group 1), 29 (37.2%) were seropositive in ELISA. Of the 90 cats from Group 2 (cats living in three geographical areas in Italy with A. abstrusus prevalence > than 10%, but negative on Baermann examination), 11 (12.2%) were positive on ELISA. The overall seroprevalence was 23.8%. There was no statistical difference either between average optical density (OD) values of cats excreting > 100 L1s vs. cats excreting < 100 L1s (0.84 vs. 0.66; P value = 0.3247) or comparing the OD values with age of infected cats. Few Baermann-negative cats positive for Toxocara cati or hookworms were seropositive, supporting lack of cross-reactivity to these nematodes.

Conclusions

Results from the present study suggest that relying solely on faecal examination may underestimate prevalence of A. abstrusus infection in cats and that field surveys based on antibody detection are useful for establishing true prevalence of infected and/or exposed animals.

Graphical Abstract
Increased gut permeability and intestinal inflammation precede arthritis onset in the adjuvant-induced model of arthritis
Authors: Hecquet Sophie , Totoson Perle , Martin Hélène , Algros Marie-Paule , Saas Philippe , Pais-de-Barros Jean-Paul , Atchon Alban , Valot Benoît , Hocquet Didier , Tournier Maude , Prati Clément , Wendling Daniel , Demougeot Céline , Verhoeven Frank
Published: June 2023

Background

Intestinal inflammation, dysbiosis, intestinal permeability (IP), and bacterial translocation (BT) have been identified in patients with spondyloarthritis but the time at which they appear and their contribution to the pathogenesis of the disease is still a matter of debate.

Objectives

To study the time-course of intestinal inflammation (I-Inf), IP, microbiota modification BT in a rat model of reactive arthritis, the adjuvant-induced arthritis model (AIA).

Methods

Analysis was performed at 3 phases of arthritis in control and AIA rats: preclinical phase (day 4), onset phase (day 11), and acute phase (day 28). IP was assessed by measuring levels of zonulin and ileal mRNA expression of zonulin. I-inf was assessed by lymphocyte count from rat ileum and by measuring ileal mRNA expression of proinflammatory cytokines. The integrity of the intestinal barrier was evaluated by levels of iFABP. BT and gut microbiota were assessed by LPS, soluble CD14 levels, and 16S RNA sequencing in mesenteric lymph node and by 16S rRNA sequencing in stool, respectively.

Results

Plasma zonulin levels increased at the preclinical and onset phase in the AIA group. Plasma levels of iFABP were increased in AIA rats at all stages of the arthritis course. The preclinical phase was characterized by a transient dysbiosis and increased mRNA ileal expression of IL-8, IL-33, and IL-17. At the onset phase, TNF-α, IL-23p19, and IL-8 mRNA expression were increased. No changes in cytokines mRNA expression were observed at the acute phase. Increased CD4+ and CD8+ T cell number was measured in the AIA ileum at day 4 and day 11. No increase in BT was observed.

Conclusion

These data show that intestinal changes precede the development of arthritis but argue against a strict “correlative” model in which arthritis and gut changes are inseparable.
Rapid activation of hematopoietic stem cells
Authors: Thapa Roshina , Elfassy Erez , Olender Leonid , Sharabi Omri , Gazit Roi
Published: June 2023

Adult hematopoietic stem cells (HSCs) in the bone marrow (BM) are quiescent. Following perturbations, such as blood loss or infection, HSCs may undergo activation. Surprisingly, little is known about the earliest stages of HSCs activation. We utilize surface markers of HSCs activation, CD69 and CD317, revealing a response as early as 2 h after stimulation. The dynamic expression of HSCs activation markers varies between viral-like (poly-Inosinic-poly-Cytidylic) or bacterial-like (Lipopolysaccharide) immune stimuli. We further quantify dose response, revealing a low threshold, and similar sensitivity of HSCs and progenitors in the BM. Finally, we find a positive correlation between the expression of surface activation markers and early exit from quiescence. Our data show that the response of adult stem cells to immune stimulation is rapid and sensitive, rapidly leading HSCs out of quiescence.
Ultrasound cavitation: a reliable non-enzymatic method for adipose-derived mesenchymal stem cell (ADSC) isolation
Authors: Park Joo-Hoo , Choi Yujin , Shin Jae-Min , Yang Hyun-Woo , Jeong Seong-Ho , Park Il-Ho
Published: June 2023

Background

Adipose tissue is known to serve as an abundant and readily accessible source of adipose-derived stem cells (ADSCs) as an alternative to bone marrow. Collagenase is one of the most widely used methods for the isolation of ADSCs from adipose tissue, but it takes a long time, and there are also debates about safety. We propose an ultrasonic cavitation-treated method that can significantly reduce time and avoid the problem of using xenogeneic enzymes in ADSCs isolation.

Methods

ADSCs were isolated from adipose tissue using the enzyme treatment method and the ultrasonic cavitation treatment method. Cell proliferation was measured using cell viability assay. The expression levels of the surface markers of ADSCs were estimated by real-time PCR. After, ADSCs were cultured in chondrogenic, osteogenic, or adipogenic differentiation medium; the differentiation potential of ADCSs was analyzed by Alcian blue, Alizarin Red S, Oil Red O, and real-time PCR.

Results

The cells treated with collagenase and ultrasound had similar cell yields and proliferation after isolation. The difference in the expression of surface markers of ADSCs was not statistically significant. ADSCs showed differentiation potential into adipocytes, osteocytes, and chondrocytes, and there was no difference between the enzyme treatment method and the ultrasonic cavitation treatment method. The yield of the ADSC increased in time- and intensity dependently.

Conclusions

Ultrasound certainly serves as a promising method in advancing ADSC isolation technology.
Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer
Authors: Ahmadi Seyed Esmaeil , Shabannezhad Ashkan , Kahrizi Amir , Akbar Armin , Safdari Seyed Mehrab , Hoseinnezhad Taraneh , Zahedi Mohammad , Sadeghi Soroush , Mojarrad Mahsa Golizadeh , Safa Majid
Published: June 2023

Tissue factor (TF) is a protein that plays a critical role in blood clotting, but recent research has also shown its involvement in cancer development and progression. Herein, we provide an overview of the structure of TF and its involvement in signaling pathways that promote cancer cell proliferation and survival, such as the PI3K/AKT and MAPK pathways. TF overexpression is associated with increased tumor aggressiveness and poor prognosis in various cancers. The review also explores TF's role in promoting cancer cell metastasis, angiogenesis, and venous thromboembolism (VTE). Of note, various TF-targeted therapies, including monoclonal antibodies, small molecule inhibitors, and immunotherapies have been developed, and preclinical and clinical studies demonstrating the efficacy of these therapies in various cancer types are now being evaluated. The potential for re-targeting TF toward cancer cells using TF-conjugated nanoparticles, which have shown promising results in preclinical studies is another intriguing approach in the path of cancer treatment. Although there are still many challenges, TF could possibly be a potential molecule to be used for further cancer therapy as some TF-targeted therapies like Seagen and Genmab’s tisotumab vedotin have gained FDA approval for treatment of cervical cancer. Overall, based on the overviewed studies, this review article provides an in-depth overview of the crucial role that TF plays in cancer development and progression, and emphasizes the potential of TF-targeted and re-targeted therapies as potential approaches for the treatment of cancer.
SYT7 regulates the progression of chronic lymphocytic leukemia through interacting and regulating KNTC1
Authors: Zhang Wenjie , Long Jinlan , Tang Peixia , Chen Kaili , Guo Guangyao , Yu Zezhong , Lin Jie , Liu Liping , Zhan Rong , Xu Zhenshu
Published: June 2023

Background

Chronic lymphocytic leukemia (CLL) is one of the most frequent occurring types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. At present, the molecular mechanism driving the pathogenesis and progression of CLL is not fully understood. The protein Synaptotagmin 7 (SYT7) encoded by the SYT7 gene has been found to be closely related to the development of various solid tumors, but its role in CLL is unclear. In this study, we investigated the function and molecular mechanism of SYT7 in CLL.

Methods

The expression level of SYT7 in CLL was determined by immunohistochemical staining and qPCR. The role of SYT7 in promoting CLL development was verified by in vivo and in vitro experiments. The molecular mechanism of SYT7 in CLL was elucidated by methods such as GeneChip analysis and Co-immunoprecipitation assay.

Results

Malignant behaviors such as proliferation, migration, and anti-apoptosis of CLL cells were significantly inhibited after SYT7 gene knockdown. In contrast, SYT7 overexpression promoted CLL development in vitro. Consistently, the knockdown of SYT7 also inhibited xenograft tumor growth of CLL cells. Mechanistically, SYT7 promoted CLL development by inhibiting SYVN1-mediated KNTC1 ubiquitination. The KNTC1 knockdown also attenuated the effects of SYT7 overexpression on development of CLL.

Conclusions

SYT7 regulates the progression of CLL through SYVN1-mediated KNTC1 ubiquitination, which has potential value for molecular targeted therapy of CLL.
Multiple cardiac surgical procedures in a case of an octogenarian with essential thrombocythemia
Authors: Maeda Motohiro , Sakamoto Shun-Ichiro , Murata Tomohiro , Hiromoto Atsushi , Suzuki Kenji , Ishii Yosuke
Published: June 2023

Background

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by an elevation of platelet counts with a tendency for thrombosis and hemorrhage. The perioperative management of cardiovascular surgery of an ET patient is complicated. There is limited literature on the perioperative management of patients with ET undergoing cardiovascular surgery, particularly those requiring multiple procedures.

Case presentation

An 85-year-old woman with a history of essential thrombocythemia (ET), which resulted in an abnormally high platelet count, was diagnosed with aortic valve stenosis, ischemic heart disease and paroxysmal atrial fibrillation. She underwent aortic valve replacement, coronary artery bypass grafting, and pulmonary vein isolation. The postoperative course was uneventful, nor hemorrhage and thrombosis.

Conclusions

We represent a case of perioperative management and successful treatment of three combined cardiac surgery for an octogenarian ET patient who is the oldest case ever reported.