bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluoxetine, fluvoxamine, and hearing loss or tinnitus after cisplatin treatment: A retrospective cohort study
Authors: Magagnoli Joseph , Cummings Tammy H. , Hardin James W. , Sutton S. Scott , Ambati Jayakrishna
Published: April 2024

Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors antidepressants, inhibit the NLR pyrin domain-containing protein 3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy. We use a retrospective cohort study within the U.S. Department of Veterans Affairs healthcare system. Adult patients with cancer who received cisplatin chemotherapy between 2000 and 2023 are included. Incidence of ototoxicity, defined by international classification of diseases revision 9-CM or international classification of diseases revision 10-CM diagnoses of hearing loss or tinnitus is compared between concurrent use of fluoxetine or fluvoxamine and cisplatin alone. A total of 20,552 patients were included. Of those, 489 received cisplatin and fluoxetine or fluvoxamine. After propensity score adjustment, the hazard of ototoxicity was lower in the group receiving fluoxetine or fluvoxamine compared to the group receiving cisplatin alone (HR = 0.62, 95% CI = (0.41–0.94)). Fluoxetine or fluvoxamine use may be associated with a reduced risk of cisplatin-induced ototoxicity. Randomized clinical trials are needed to confirm these findings and establish the efficacy of the medications in ototoxicity prevention. Further research is also warranted to investigate the potential mechanisms underlying this protective effect.
Association of statins with nonalcoholic fatty liver disease in patients with diabetes
Authors: Shah Raj , Kong Alexander , De Melo Silvio , Boktor Moheb , Henriquez Richard , Mandalia Amar , Samant Hrishikesh , Alvarez Carlos A. , Mansi Ishak A.
Published: April 2024

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in patients with diabetes; limited data suggested that statins may reduce the risk of NAFLD progression. This study aimed to examine the association between statins and the development or progression of NAFLD in veterans with diabetes. In a new-user negative control design, we conducted a retrospective propensity score (PS)-matched cohort study of patients with diabetes between 2003 and 2015. After excluding patients with other causes of liver disease, we formed PS using 85 characteristics. The primary outcome was a composite NAFLD progression outcome. Primary analysis examined odds of outcome in PS-matched cohort. Post-hoc analysis included a PS-matched cohort of statin users with intensive lowering of low-density lipoprotein-cholesterol (LDL-C) vs low-intensity lowering. We matched 34,102 pairs from 300,739 statin users and 38,038 non-users. The composite outcome occurred in 8.8% of statin users and 8.6% of non-users (odds ratio (OR) 1.02, 95% confidence interval (95% CI) 0.97–1.08). In the post-hoc analysis, intensive lowering of LDL-C compared to low-intensity showed increased NAFLD progression (OR 1.21, 95% CI 1.13–1.30). This study showed that statin use in patients with diabetes was not associated with decreased or increased risk of NAFLD progression. Intensive LDL-C lowering, compared to low-intensity LDL-C lowering, was associated with an increased risk of NAFLD progression.
Who Do the Socially Mobile Vote For? A Longitudinal Analysis of Intergenerational Mobility and Political Preferences
Authors: Jerrim John , Kaye Neil
Published: April 2024

Social mobility has become a key public policy issue across the Western world. But who do the upwardly and downwardly mobile vote for? Does their voting behaviour remain the same as their peers in their social origin class, or does it quickly assimilate to mimic the behaviour of others at their social destination? This article presents new, longitudinal evidence on this issue, documenting how the link between social origin, destination and political voting behaviour varies during adult life. We find individuals who move up the social ladder are more likely to vote Conservative than individuals who remain in the same social class as their parents. Overall, an individual’s social origin and social destination seem to be equally important for how they vote. Yet we find no evidence that social mobility is associated with political voting preferences per se; rather upwardly mobile individuals’ greater propensity to vote for the Conservatives is driven by the joint impact of their social origin and destination.
The play of education and market: A literature review on the roles commercial actors play for K-12 education
Authors: Verelst Sukriti , Simons Maarten , Berghmans Mieke
Published: April 2024

There has been an abundance of research on commercial actors in education. However, there has hardly been any attempt to streamline the existing ways of thinking about their presence and activity in the field of education. Therefore, the purpose of this article is to do a comprehensive literature review on the involvement of commercial actors in K-12 education. A total of 157 articles published between 2000 and 2023 were reviewed and “involvement of commercial actors in education” was operationalized as the roles they play in education. The research questions answered in this review were as follows: (i) What are the key perspectives that are addressed by researchers regarding the involvement of commercial actors in K-12 education? (ii) Which roles do commercial actors play in K-12 education and what are the issues being raised by researchers regarding each role? Three perspectives when it comes to research on involvement of commercial actors in education were identified: how commercial actors are changing the organization and functioning of K-12 education; how commercial actors are changing the organization and functioning of the education market; and the interaction between school actors and commercial actors. Under each perspective, various roles played by commercial actors were identified. The article demonstrated the multiplicity and diversity in the identified roles and also delved into the need to go beyond any reductionist understanding of commercial actors’ involvement in education. The multiple roles outlined in this review show how commercial actors’ involvement requires disentangling through novel approaches and how their inter-action with education creates the need to ask other important questions about the role of education itself and its key values and principles.
The ballistic performance of plain-weave multi-ply systems: An experimental investigation
Authors: Xu Lizhi , Zhou Xuan , Ren Wenke , Zhang Rui , Zhou Yi , Gao Guangfa
Published: April 2024

This paper studies the influence of the weave parameter on the ballistic performance of multi-ply systems. Three types of plain weaves were put into investigation, namely, A090, A200, and A400. Tensile and yarn pull-out tests were performed to investigate the responses of fabric upon quasi-static loading. Penetration tests were performed to characterize the energy absorption capability of different multi-ply systems at impacting velocities ranging from 250 m/s to 460 m/s. It was found that the strength of the fabric sample increased almost linearly with fabric areal density, and the coarser weaves exhibited a greater resistance against yarn pull-out. The ballistic limit ( V50) of finer weave 13A9, is around than 42.5% higher than coarser weave 3A4. In terms of hybrid systems, placing finer fabrics in front and coarser fabrics in the rear exhibits higher ballistic limits than the reversed sequence (8–20 m/s differences), while placing coarser fabrics in front exhibited greater energy absorption capability when the impact velocity is sufficient to cause instant and localized failure. It was also found that the ballistic performance of the hybrid systems does not alter significantly with the mass percentage of the coarser weaves at high impact velocities (greater than 400 m/s). The results indicate that replacing the expensive ballistic weaves with cheap materials in a hybrid system is a reasonable alternative to achieve cost reduction without significant performance degradation.
Gatekeeping the Gatekeepers: An Exploratory Study of Transformative Games Fandom & TikTok Algorithms
Authors: Tompkins Jessica E. , Guajardo (née Brown) Ashley ML
Published: April 2024

Within fandoms, gatekeeping practices such as delineating authentic from fake fans filter out certain identities. While the types of fans excluded vary by fandom, mainstream digital games culture–and the hegemonic, masculine groups within it–frequently leverage gatekeeping tactics like harassment to silence or churn others (i.e., women) from participating. While there has been considerable scholarship documenting gatekeeping in online digital games there has been less examination of this occurring within video game fandom. We conducted an exploratory study to investigate gatekeeping in response to TikTok videos about Call of Duty's masculine operator Ghost. We found more comments qualifying as celebratory fun than gatekeeping. We argue that social media spaces by virtue of their recommendation algorithms are productive sites for reimagining games counter to affirmational readings within relatively niche communities.
Whole Health Revolution: Value-Based Care + Lifestyle Medicine
Authors: Johnson Karen S. , Patel Padmaja
Published: April 2024

An outdated and burdensome fee-for-service (FFS) reimbursement system has significantly compromised primary care delivery in the US for decades, leading to a dire shortage of primary care workers. Support for primary care must increase from all public and private payers with well-designed value-based primary care payment. Patient care enabled by value-based payment is typically described or “labeled” as value-based care and commonly viewed as distinctly different from other models of care delivery. Unfortunately, labels tend to put individuals in camps that can make the differences seem greater than they are in practice. Achieving the aims of value-based care, aligned with the quintuple aims of health care, is common across many delivery models. The shrinking primary care workforce is too fragile to be fragmented across competing camps. Seeing the alignment across otherwise separate disciplines, such as lifestyle medicine and value-based care, is essential. In this article, we point to the opportunities that arise when we widen the lens to look beyond these labels and make the case that a variety of models and perspectives can meld together in practice to produce the kind of high-quality primary care physicians, care teams, and patients are seeking.
Developing a Personalized Educational Leadership Theory: A Promising Approach to School Leadership Development?
Authors: Lipscombe Kylie , Tindall-Ford Sharon , Kidson Paul
Published: April 2024

Behind every school leader is an individual with experiences. These experiences, personal and professional, shape how an educator conceptualizes leadership. This study examines the types of experiences that leaders, enrolled in a Master of Educational Leadership degree in Australia, draw on to inform their leadership. The findings reveal four key experiences that influence the way school leaders view and practice leadership: experiential; educative; vicarious; and personal. We discuss how the medium of digital story supports school leaders to develop their personalized educational leadership theory (PELT) as part of educational leadership development.
PhD stipends and program placement success in political science
Authors: Warner Seth B. , Stecuła Dominik A.
Published: April 2024

A key grievance of the student labor movement is that across much of academia, and especially in the social sciences and humanities, stipends tied to PhD assistantships fall short of a living wage. In this article, we consider the issue from a pedagogical perspective, expecting that higher pay may lead to stronger program outcomes. We collect and validate data on assistantship stipends in political science from PhDStipends.com, and on tenure-track placements from an analysis of departmental placement pages. Graduate pay is significantly associated with tenure-track placements in the job market cycles spanning 2019–2021, independently of program size, rank, student unionization, location, and institution type and endowment. Across model specifications, a US$5,000 increase in student pay corresponds with 2.7 more placements per 100 enrolled students (or 34% of the median rate) over this period.
Mapping the Dynamic Complexity of Social Isolation Among Older Adults in Singapore
Authors: Shuen Toh Emma Min , Wei-Yan Chia Aloysius , Ansah John P.
Published: April 2024

This study aims to develop a causal map of social isolation among older people that incorporates feedback to inform system-wide interventions. For this study, conducted between September 2019 and November 2019, 19 Senior Activity Centres (SACs) were first contacted, of which 10 responded and 5 agreed to participate. Based on an in-depth qualitative interview with 21 older people (50 years and older) who frequently attended Senior Activity Centres (SACs) in Singapore, a series of causal maps were generated and synthesized to describe the complex dynamic mechanisms of social isolation. Using thematic analysis based on grounded theory, 13 feedback loops (outputs of a system routed back as inputs as part of a chain of cause-and-effect) were elicited and categorized into 4 domains: (a) health and wellbeing, (b) income and unemployment, (c) relationships with family and friends, and (d) behavior and personality. These domains were found to be the most salient factors influencing social isolation. A qualitative mapping approach based on System Dynamics Methodology can provide a comprehensive understanding of the system-level factors of social isolation among older people.
Improvement in Clinical and Radiographic Outcomes After Isolated Realignment Surgery in Patients With Large Cystic Osteochondral Lesion of the Talar Shoulder and Concurrent Malalignment
Authors: Kim Jaeyoung , Yi Young , Lee Woo-Chun
Published: April 2024

Background:

Malalignment has been suggested as a predisposing factor for the development of osteochondral lesions of the talus (OLTs).

Purpose:

To evaluate the clinical and radiographic outcomes of realignment surgery in patients with a large cystic OLT of the talar shoulder and concurrent malalignment of the foot and ankle.

Study Design:

Case series; Level of evidence, 4.

Methods:

The authors reviewed consecutive patients with large cystic OLTs (diameter, >10 mm) of the talar shoulder and concurrent malalignment of the foot and ankle who underwent realignment surgery between September 2013 and April 2021. The type of realignment procedure was determined based on patient symptoms and findings on plain radiographs and weightbearing computed tomography. Clinical improvement was assessed using pre- and postoperative Foot Function Index (FFI) scores and the visual analog scale (VAS) for pain. The OLT location was categorized according to Raikin zone, and the OLT area and volume were measured and compared pre- and postoperatively. The comparative analysis was performed using the Wilcoxon signed-rank test.

Results:

In total, 27 ankles in 27 patients (mean age, 34.4 ± 11.9 years) were included in the analysis. There were 25 patients with a medial lesion (zone 4 [n = 19], zone 7 [n = 5], and zone 1 [n = 1]), and 2 patients with a lateral lesion (zone 6). Despite OLT location, patients’ symptoms varied; 15 (55.6%) patients reported both medial- and lateral-sided pain, 10 (37%) reported lateral-sided pain, and 2 (7%) reported medial-sided pain. Supramalleolar osteotomy was performed in 18 patients, while foot and hindfoot correction without supramalleolar osteotomy was performed in 9 patients. Postoperatively, both the median FFI (from 44.4 [interquartile range (IQR), 35.7-52.2] to 9.1 [IQR, 5.2-13.9]) and median VAS pain score (from 6 [IQR, 5-6] to 1 [IQR, 1-2]) improved significantly ( P < .0001 for both), and the median lesion size (from 25.8 mm2 [IQR, 19.3-45.2 mm2] to 13.8 mm2 [IQR, 6.8-26.5 mm2]) and median volume (from 2226.8 mm3 [IQR, 1311-3104 mm3] to 1326.5 mm3 [IQR, 714-2100 mm3]) decreased significantly ( P < .0001 for both). During the mean follow-up of 4.1 ± 2.1 years, no subsequent surgery for OLT was necessary.

Conclusion:

The results suggest that realignment procedures can improve the symptoms and radiographic profile of OLTs in patients with large cystic OLTs of the talar shoulder and malalignment of the foot and ankle.
NSD2 drives t(4;14) myeloma cell dependence on adenylate kinase 2 by diverting one-carbon metabolism to the epigenome
Authors: Sobh Amin , Encinas Elena , Patel Alisha , Surapaneni Greeshma , Bonilla Emilie , Kaestner Charlotte , Poullard Janai , Clerio Monica , Vasan Karthik , Freeman Tzipporah , Lv Dongwen , Dupéré-Richer Daphné , Riva Alberto , Barwick Benjamin G. , Zhou Daohong , Boise Lawrence H. , Mitsiades Constantine S. , Kim Baek , Bennett Richard L. , Chandel Navdeep S. , Licht Jonathan D.
Published: April 2024

Chromosomal translocation (4;14), an adverse prognostic factor in multiple myeloma (MM), drives overexpression of the histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2). A genome-wide CRISPR screen in MM cells identified adenylate kinase 2 (AK2), an enzyme critical for high-energy phosphate transfer from the mitochondria, as an NSD2-driven vulnerability. AK2 suppression in t(4;14) MM cells decreased nicotinamide adenine dinucleotide phosphate (NADP[H]) critical for conversion of ribonucleotides to deoxyribonucleosides, leading to replication stress, DNA damage, and apoptosis. Driving a large genome-wide increase in chromatin methylation, NSD2 overexpression depletes S-adenosylmethionine, compromising the synthesis of creatine from its precursor, guanidinoacetate. Creatine supplementation restored NADP(H) levels, reduced DNA damage, and rescued AK2-deficient t(4;14) MM cells. As the creatine phosphate shuttle constitutes an alternative means for mitochondrial high-energy phosphate transport, these results indicate that NSD2-driven creatine depletion underlies the hypersensitivity of t(4;14) MM cells to AK2 loss. Furthermore, AK2 depletion in t(4;14) cells impaired protein folding in the endoplasmic reticulum, consistent with impaired use of mitochondrial adenosine triphosphate (ATP). Accordingly, AK2 suppression increased the sensitivity of MM cells to proteasome inhibition. These findings delineate a novel mechanism in which aberrant transfer of carbon to the epigenome creates a metabolic vulnerability, with direct therapeutic implications for t(4;14) MM.
Patterns of CRS with teclistamab in relapsed/refractory multiple myeloma with or without prior T-cell redirection therapy
Authors: Hamadeh Issam S. , Shekarkhand Tala , Rueda Colin , Firestone Ross S. , Wang Alice X. , Korde Neha , Hultcrantz Malin L. , Lesokhin Alexander M. , Mailankody Sham , Hassoun Hani , Shah Urvi A. , Maclachlan Kylee , Rajeeve Sridevi , Patel Dhwani , Shah Gunjan L. , Scordo Michael , Lahoud Oscar B. , Chung David J. , Landau Heather J. , Giralt Sergio , Usmani Saad Z. , Tan Carlyn R.
Published: April 2024

Teclistamab (Tec) is a first-in-class BCMA × CD3 bispecific T-cell engager antibody approved for treating multiple myeloma progressing after at least 4 lines of therapy. The objective of this study was to evaluate the rate of cytokine release syndrome (CRS) in patients who were treated with commercial Tec and had prior exposure to other T-cell redirection therapies. A retrospective chart review was performed to identify patients who completed the Tec step-up dosing phase between November 2022 and November 2023. Patients were divided into 2 cohorts based on prior exposure to T-cell redirection therapy (cohort 1: T-cell redirection therapy experienced; cohort 2: T-cell redirection therapy naïve). The primary objective was to compare the differences in the rates of CRS between the 2 cohorts. Univariate and multivariate logistic regression analyses were performed to assess the association between CRS rates with Tec and prior treatment with T-cell redirection therapy. A total of 72 patients were included in the analysis (27 in cohort 1 and 45 in cohort 2). The CRS rates were significantly lower in cohort 1 (37%, n = 10) compared with cohort 2 (80%, n = 36; P = .0004). Based on multivariate logistic regression analysis, patients without prior exposure to T-cell redirection therapy (cohort 2) had about a fourfold increase in the incidence of CRS (95% confidence interval, 1.40-14.90; P = .0002) with Tec. In our study, prior exposure to T-cell redirection therapy reduced the risk of CRS with Tec during the step-up dosing phase. This observation will allow for the optimization of CRS prophylactic strategies for Tec.
Does local soil factor drive functional leaf trait variation? A test on Neilingding Island, South China
Authors: Tong Sen , Zhang Juanjuan , Qiao Xueting , Li Buhang , Yang Qiong , Hu Ping , Yu Shixiao
Published: April 2024

Leaf traits were affected by soil factors and displayed varietal differences in forest. However, few examples have been reported on the Island ecosystems. We comprehensively investigated 9 leaf traits (leaf length, leaf width, leaf area, SLA, leaf fresh weight, leaf C content, leaf N content, leaf K content, leaf C:N ratio) of 54 main subtropical woody species and soil parameters (soil pH, total C content, total N content, total K content, available N content, available P content, available K content and soil moisture) in Neilingding Island, Shenzhen, southern China. Intra-and interspecific variation of leaf traits were measured and their correlations with soil parameters were explored. The interspecific variations of leaf C:N ratio, leaf N content and leaf fresh weight were higher than their intraspecific variations. The intraspecific variation of leaf K content was larger than that of interspecific one, accounting for 80.69% of the total variance. Positive correlations were found among intraspecific coefficients of variations in leaf morphological traits. The correlation analysis between the variation of intraspecific traits and the variation of soil parameters showed that changes in soil factors affected leaf morphology and stoichiometry. The interaction between soil moisture and soil available P content was the key factor on intraspecific variations of leaf traits including leaf area, leaf fresh weight, leaf C and leaf K content. We concluded that leaf traits of plants in the island were tightly related to soil parameters. Soil parameters, especially soil moisture and available P content, affected plant leaf morphology and stoichiometry at the local scale.
Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection
Authors: Ganjo Aryan R. , Balaky Salah Tofik Jalal , Mawlood Ahang Hasan , Smail Sakar B. , Shabila Nazar P.
Published: April 2024

Background

Escherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin.

Methods

A total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated.

Results

The E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin.

Conclusions

The antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates.
Analysis of endophytic bacterial diversity in seeds of different genotypes of cotton and the suppression of Verticillium wilt pathogen infection by a synthetic microbial community
Authors: Wu Chong-Die , Fan Yong-Bin , Chen Xue , Cao Jiang-Wei , Ye Jing-Yi , Feng Meng-Lei , Liu Xing-Xing , Sun Wen-Jing , Liu Rui-Na , Wang Ai-Ying
Published: April 2024

Background

In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat.

Results

This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens.

Conclusion

This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.
The genome of Citrus australasica reveals disease resistance and other species specific genes
Authors: Nakandala Upuli , Furtado Agnelo , Masouleh Ardashir Kharabian , Smith Malcolm W. , Williams Darren C. , Henry Robert J.
Published: April 2024

Background

The finger lime (Citrus australasica), one of six Australian endemic citrus species shows a high natural phenotypic diversity and novel characteristics. The wide variation and unique horticultural features have made this lime an attractive candidate for domestication. Currently no haplotype resolved genome is available for this species. Here we present a high quality, haplotype-resolved reference genome for this species using PacBio HiFi and Hi-C sequencing.

Results

Hifiasm assembly and SALSA scaffolding resulted in a collapsed genome size of 344.2 Mb and 321.1 Mb and 323.2 Mb size for the two haplotypes. The nine pseudochromosomes of the collapsed genome had an N50 of 35.2 Mb, 99.1% genome assembly completeness and 98.9% gene annotation completeness (BUSCO). A total of 41,304 genes were predicted in the nuclear genome. Comparison with C. australis revealed that 13,661 genes in pseudochromosomes were unique in C. australasica. These were mainly involved in plant-pathogen interactions, stress response, cellular metabolic and developmental processes, and signal transduction. The two genomes showed a syntenic arrangement at the chromosome level with large structural rearrangements in some chromosomes. Genetic variation among five C. australasica cultivars was analysed. Genes related to defense, synthesis of volatile compounds and red/yellow coloration were identified in the genome. A major expansion of genes encoding thylakoid curvature proteins was found in the C. australasica genome.

Conclusions

The genome of C. australasica present in this study is of high quality and contiguity. This genome helps deepen our understanding of citrus evolution and reveals disease resistance and quality related genes with potential to accelerate the genetic improvement of citrus.
Amide proton transfer weighted and diffusion weighted imaging based radiomics classification algorithm for predicting 1p/19q co-deletion status in low grade gliomas
Authors: Ma Andong , Yan Xinran , Qu Yaoming , Wen Haitao , Zou Xia , Liu Xinzi , Lu Mingjun , Mo Jianhua , Wen Zhibo
Published: April 2024

Background

1p/19q co-deletion in low-grade gliomas (LGG, World Health Organization grade II and III) is of great significance in clinical decision making. We aim to use radiomics analysis to predict 1p/19q co-deletion in LGG based on amide proton transfer weighted (APTw), diffusion weighted imaging (DWI), and conventional MRI.

Methods

This retrospective study included 90 patients histopathologically diagnosed with LGG. We performed a radiomics analysis by extracting 8454 MRI-based features form APTw, DWI and conventional MR images and applied a least absolute shrinkage and selection operator (LASSO) algorithm to select radiomics signature. A radiomics score (Rad-score) was generated using a linear combination of the values of the selected features weighted for each of the patients. Three neuroradiologists, including one experienced neuroradiologist and two resident physicians, independently evaluated the MR features of LGG and provided predictions on whether the tumor had 1p/19q co-deletion or 1p/19q intact status. A clinical model was then constructed based on the significant variables identified in this analysis. A combined model incorporating both the Rad-score and clinical factors was also constructed. The predictive performance was validated by receiver operating characteristic curve analysis, DeLong analysis and decision curve analysis. P < 0.05 was statistically significant.

Results

The radiomics model and the combined model both exhibited excellent performance on both the training and test sets, achieving areas under the curve (AUCs) of 0.948 and 0.966, as well as 0.909 and 0.896, respectively. These results surpassed the performance of the clinical model, which achieved AUCs of 0.760 and 0.766 on the training and test sets, respectively. After performing Delong analysis, the clinical model did not significantly differ in predictive performance from three neuroradiologists. In the training set, both the radiomic and combined models performed better than all neuroradiologists. In the test set, the models exhibited higher AUCs than the neuroradiologists, with the radiomics model significantly outperforming resident physicians B and C, but not differing significantly from experienced neuroradiologist.

Conclusions

Our results suggest that our algorithm can noninvasively predict the 1p/19q co-deletion status of LGG. The predictive performance of radiomics model was comparable to that of experienced neuroradiologist, significantly outperforming the diagnostic accuracy of resident physicians, thereby offering the potential to facilitate non-invasive 1p/19q co-deletion prediction of LGG.
Biplex quantitative PCR to detect transcriptionally active human papillomavirus 16 from patient saliva
Authors: Deutsch Fiona , Sais Dayna , Keatinge Ni , Hill Meredith , Tran Ngoc Ha , Elliott Michael , Tran Nham
Published: April 2024

Head and neck cancers, particularly oropharyngeal cancers (OPC), have been increasingly associated with human papillomavirus (HPV) infections, specifically HPV16. The current methods for HPV16 detection primarily rely on p16 staining or PCR techniques. However, it is important to note the limitations of conventional PCR, as the presence of viral DNA does not always indicate an ongoing viral infection. Moreover, these tests heavily rely on the availability of tissue samples, which can present challenges in certain situations. In this study, we developed a RT-qPCR biplex approach to detect HPV16 oncogenes E6 and E7 RNA in saliva samples from OPC patients. Salivary supernatant was used as the liquid biopsy source. We successfully obtained RNA from salivary supernatant, preserving its integrity as indicated by the detection of several housekeeping genes. Our biplex approach accurately detected E6 and E7 RNA in HPV16-positive cell lines, tissues, and finally in OPC salivary samples. Importantly, the assay specifically targeted HPV16 and not HPV18. This biplexing technique allowed for reduced sample input without compromising specificity. In summary, our approach demonstrates the potential to detect viable HPV16 in saliva from OPC patients. Since the assay measures HPV16 RNA, it provides insights into the transcriptional activity of the virus. This could guide clinical decision-making and treatment planning for individuals with HPV-related OPC.
Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy
Authors: Wang Hanbing , Zhang Xin , Zhang Yipeng , Shi Tao , Zhang Yue , Song Xueru , Liu Baorui , Wang Yue , Wei Jia
Published: April 2024

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted.

Methods

The potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified.

Results

Our results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy.

Conclusions

Conclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells.

This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.
Identification of stemness-related glycosylation changes in head and neck squamous cell carcinoma
Authors: Routila E , Mahran R , Salminen S , Irjala H , Haapio E , Kytö E , Ventelä S , Petterson K , Routila J , Gidwani K , Leivo J
Published: April 2024

Background

Altered glycosylation is a hallmark of cancer associated with therapy resistance and tumor behavior. In this study, we investigated the glycosylation profile of stemness-related proteins OCT4, CIP2A, MET, and LIMA1 in HNSCC tumors.

Methods

Tumor, adjacent normal tissue, and blood samples of 25 patients were collected together with clinical details. After tissue processing, lectin-based glycovariant screens were performed.

Results

Strong correlation between glycosylation profiles of all four stemness-related proteins was observed in tumor tissue, whereas glycosylation in tumor tissue, adjacent normal tissue, and serum was differential.

Conclusions

A mannose- and galactose-rich glycosylation niche associated with stemness-related proteins was identified.
Elevated ADH5 expression suggested better prognosis in kidney renal clear cell carcinoma (KIRC) and related to immunity through single-cell and bulk RNA-sequencing
Authors: Sun Junhao , Zhang Xinyu , Wu Fan , Zhu Bingye , Xie Huyang
Published: April 2024

Background

Despite the rapid advances in modern medical technology, kidney renal clear cell carcinoma (KIRC) remains a challenging clinical problem in urology. Researchers urgently search for useful markers to break through the therapeutic conundrum due to its high lethality. Therefore, the study explores the value of ADH5 on overall survival (OS) and the immunology of KIRC.

Methods

The gene expression matrix and clinical information on ADH5 in the TCGA database were validated using external databases and qRT-PCR. To confirm the correlation between ADH5 and KIRC prognosis, univariate/multivariate Cox regression analysis was used. We also explored the signaling pathways associated with ADH5 in KIRC and investigated its association with immunity.

Results

The mRNA and protein levels showed an apparent downregulation of ADH5 in KIRC. Correlation analysis revealed that ADH5 was directly related to histological grade, clinical stage, and TMN stage (p < 0.05). Univariate and multivariate Cox regression analysis identified ADH5 as an independent factor affecting the prognosis of KIRC. Enrichment analysis looked into five ADH5-related signaling pathways. The results showed no correlation between ADH5 and TMB, TNB, and MSI. From an immunological perspective, ADH5 was found to be associated with the tumor microenvironment, immune cell infiltration, and immune checkpoints. Lower ADH5 expression was associated with greater responsiveness to immunotherapy. Single-cell sequencing revealed that ADH5 is highly expressed in immune cells.

Conclusion

ADH5 could be a promising prognostic biomarker and a potential therapeutic target for KIRC. Besides, it was found that KIRC patients with low ADH5 expression were more sensitive to immunotherapy.
Biometric analysis of furcation area of molar teeth and its relationship with instrumentation
Authors: Mukherjee Mun , Nair Vineet , Phull Tanvi , Jain Ashish , Grover Vishakha , Ali Ahmed Babiker Mohamed , Arora Suraj , Das Gotam , Hassan Saeed Awod Bin , Sainudeen Shan , Saluja Priyanka
Published: April 2024

The anatomy of furcation favours the bacterial retention and makes periodontal debridement as well as oral hygiene procedures difficult. Teeth that have lost attachment to a level of the furcation are said to have a furcal invasion or furcation involved.

Involvement of furcation in a multi-rooted tooth poses a very different type of clinical situation in terms of establishment of diagnosis, determination of prognosis and of course planning the treatment modality.The present study was carried out on 200 selected extracted human first and second permanent molar teeth based on a predefined criteria. Teeth with prosthetic crowns, fused or fractured roots, those not fully developed, grossly carious or heavily restored at the cementoenamel junction (CEJ) were excluded from the study. The morphology of the root trunk was recorded by measuring various dimensions of the root trunk,including furcal angle and root trunk volume was calculated by using a custom made special apparatus. The furcation areas were debrided with different types of curettes in the market in order to see how best the instrument could be maneuvered in the furcation area. The data so obtained was statistically analysed using SPSS version 22. The highest root trunk volume and the longest root trunk length were found to be in the maxillary second molar. 48.60% furcations didn’t allow instrument engagementof furcation area with standard area specific curettes. The proposal of inclusion of root trunk length (mm) is suggested in addition to classification ofFIto have assess prognosis and appropriate treatment for of the involved tooth.
Cultural adaptation and validation of the caring behaviors assessment tool into Spanish
Authors: Leyva-Moral Juan M. , Watson Carolina , Granel Nina , Raij-Johansen Cecilia , Ayala Ricardo A.
Published: April 2024

Background

The aim of the research was to translate, culturally adapt and validate the Caring Behaviors Assessment (CBA) tool in Spain, ensuring its appropriateness in the Spanish cultural context.

Methods

Three-phase cross-cultural adaptation and validation study. Phase 1 involved the transculturation process, which included translation of the CBA tool from English to Spanish, back-translation, and refinement of the translated tool based on pilot testing and linguistic and cultural adjustments. Phase 2 involved training research assistants to ensure standardized administration of the instrument. Phase 3 involved administering the transculturally-adapted tool to a non-probabilistic sample of 402 adults who had been hospitalized within the previous 6 months. Statistical analyses were conducted to assess the consistency of the item-scale, demographic differences, validity of the tool, and the importance of various caring behaviors within the Spanish cultural context. R statistical software version 4.3.3 and psych package version 2.4.1 were used for statistical analyses.

Results

The overall internal consistency of the CBA tool was high, indicating its reliability for assessing caring behaviors. The subscales within the instrument also demonstrated high internal consistency. Descriptive analysis revealed that Spanish participants prioritized technical and cognitive aspects of care over emotional and existential dimensions.

Conclusions

The new version of the tool proved to be valid, reliable and culturally situated, which will facilitate the provision of objective and reliable data on patients beliefs about what is essential in terms of care behaviors in Spain.
Patients’ perspectives on quality and patient safety failures: lessons learned from an inquiry into transvaginal mesh in Australia
Authors: Motamedi Mina , Degeling Chris , M. Carter Stacy
Published: April 2024

Background

Transvaginal mesh (TVM) surgeries emerged as an innovative treatment for stress urine incontinency and/or pelvic organ prolapse in 1996. Years after rapid adoption of these surgeries into practice, they are a key example of worldwide failure of healthcare quality and patient safety. The prevalence of TVM-associated harms eventually prompted action globally, including an Australian Commonwealth Government Senate Inquiry in 2017.

Method

We analysed 425 submissions made by women (n = 417) and their advocates (n = 8) to the Australian Senate Inquiry, and documents from 5 public hearings, using deductive and inductive coding, categorisation and thematic analysis informed by three ‘linked dilemmas’ from healthcare quality and safety theory. We focused on women’s accounts of: a) how harms arose from TVM procedures, and b) micro, meso and macro factors that contributed to their experience. Our aim was to explain, from a patient perspective, how these harms persisted in Australian healthcare, and to identify mechanisms at micro, meso and macro levels explaining quality and safety system failure.

Results

Our findings suggest three mechanisms explaining quality and safety failure: 1. Individual clinicians could ignore cases of TVM injury or define them as ‘non-preventable’; 2. Women could not go beyond their treating clinicians to participate in defining and governing quality and safety; and. 3. Health services set thresholds for concern based on proportion of cases harmed, not absolute number or severity of harms.

Conclusion

We argue that privileging clinical perspectives over patient perspectives in evaluating TVM outcomes allowed micro-level actors to dismiss women’s lived experience, such that women’s accounts of harms had insufficient or no weight at meso and macro levels. Establishing system-wide expectations regarding responsiveness to patients, and communication of patient reported outcomes in evaluation of healthcare delivery, may help prevent similar failures.
Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease
Authors: Lestelle François , Beigelman Catherine , Rotzinger David , Si-Mohamed Salim , Nasser Mouhamad , Wemeau Lidwine , Hirschi Sandrine , Prevot Grégoire , Roux Antoine , Bunel Vincent , Gomez Emmanuel , Sohier Laurent , Pradier Helene Morisse , Gaubert Martine Reynaud , Gondouin Anne , Lazor Romain , Glerant Jean-Charles , Bejui Françoise Thivolet , Colombat Magali , Cottin Vincent ,   the OrphaLung network, Uzunhan Yurdagül , Jouneau Stéphane
Published: April 2024

Background

Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs.

Study design and methods

A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry.

Results

Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005).

Conclusions

Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.