bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern‐centric transformation of omics data grounded on discriminative gene associations aids predictive tasks in TCGA while ensuring interpretability
Authors: Patrício André , Costa Rafael S. , Henriques Rui
Published: June 2024

The increasing prevalence of omics data sources is pushing the study of regulatory mechanisms underlying complex diseases such as cancer. However, the vast quantities of molecular features produced and the inherent interplay between them lead to a level of complexity that hampers both descriptive and predictive tasks, requiring custom‐built algorithms that can extract relevant information from these sources of data. We propose a transformation that moves data centered on molecules (e.g., transcripts and proteins) to a new data space focused on putative regulatory modules given by statistically relevant co‐expression patterns. To this end, the proposed transformation extracts patterns from the data through biclustering and uses them to create new variables with guarantees of interpretability and discriminative power. The transformation is shown to achieve dimensionality reductions of up to 99% and increase predictive performance of various classifiers across multiple omics layers. Results suggest that omics data transformations from gene‐centric to pattern‐centric data supports both prediction tasks and human interpretation, notably contributing to precision medicine applications.
Tumor treating fields for newly diagnosed high‐grade glioma based on the criteria of 2021 WHO CNS5: A retrospective analysis of Chinese patients in a single center
Authors: Zhang Li , Ren Yanming , Peng Youheng , Luo Yong , Liu Yanhui , Wang Xiang , Yang Yuan , Liu Lei , Ai Ping , Yang Xiaoyan , Li Yanchu , Mao Qing , Wang Feng
Published: June 2024

Background and Objective

High‐grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium‐frequency, low‐intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center.

Methods

We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non‐TTFields group. Progression‐free survival (PFS) and overall survival (OS) were compared between the two groups.

Results

There were 26 cases in the TTFields group and 26 cases in the non‐TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50–18.90), the median OS was 19.7 months (95% CI: 14.95–24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47–4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57–11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non‐TTFields group, the median PFS was 9.57 months (95% CI: 6.23–12.91) and the median OS was 16.07 months (95% CI: 12.90–19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups.

Conclusions

In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.
Identification ofPSMD11as a novel cuproptosis‐ and immune‐related prognostic biomarker promoting lung adenocarcinoma progression
Authors: Huang Qiumin , Tian Ran , Yu Jinxi , Du Wei
Published: June 2024

Background

Due to the unfavorable prognosis associated with lung adenocarcinoma (LUAD), the development of targeted therapies and immunotherapies is essential. Cuproptosis, an emerging form of regulated cell death, is implicated in mitochondrial metabolism and is induced by copper ions. This study aimed to explore the prognostic value of cuproptosis‐ and immune‐related genes (CIRGs) in LUAD.

Methods

We used The Cancer Genome Atlas database to develop a prognostic prediction model for LUAD patients based on eight CIRGs. Using Cox regression analysis, we determined that the CIRG signature is a reliable, independent prognostic factor. We further identifiedPSMD11as a critical CIRG and performed immunohistochemistry to study the protein expression levels of PSMD11 in LUAD tissues. We also investigated the impact of PSMD11 on the biological behavior of lung cancer cell lines.

Results

We found that patients with low PSMD11 expression levels displayed an improved prognosis compared with those with high PSMD11 expression levels. Overexpression ofPSMD11enhanced proliferation, migration, invasion, and tumor growth of lung carcinoma cell line A549, whilePSMD11knockdown diminished proliferation, migration, invasion, and tumor growth of lung carcinoma cell line PC9. Additionally, we discovered thatPSMD11expression was positively correlated with the infiltration of myeloid‐derived suppressor cells and the increased expression of immunosuppressive molecules.

Conclusion

These findings suggest thatPSMD11may serve as a valuable prognostic biomarker and therapeutic target for LUAD.
Client subgroups in emotion‐focussed therapy: Exploring profiles in observable emotion
Authors: Pascual‐Leone Antonio , Cristoffanini Florencia , Sawashima Tsubasa
Published: June 2024

Objective

The present study examined client profiles in observed emotion to explore possible subgroups among clients given that there is substantial heterogeneity in clients' expression of emotion in therapy. Subgroups were identified using the sequential model of emotional processing, which posits that global distress, shame/fear and rejecting anger represent ‘early expressions of distress’, whereas assertive anger, self‐compassion and grief/hurt are conceptualised to be ‘adaptive states’ that predict good outcomes. The present study also offers a unique strategy for studying differences in clients' emotional presentation with implications for within‐session assessment by therapists.

Method

Sections of videotaped therapy sessions for 34 participants in emotion‐focussed therapy were coded for each emotional state. Through cluster analysis, participants were grouped based on the relative magnitude of each emotion state in the model.

Results

In the first set of analyses, two naturalistic groups were formed: Cluster 2 had higher levels of adaptive emotion and rejecting anger than Cluster 1. There was a significantly greater proportion of good within‐session outcomes in Cluster 2 than in Cluster 1. In the second set of analyses, a separate cluster analysis categorised participants based on their early expressions of distress. Four groups were described as follows: Distressed, Protesters, Fearful & Ashamed and Minimally Distressed. Only the Minimally Distressed group showed significantly higher rates of good within‐session outcome.

Discussion

These findings provide support for the emotional processing model by using novel methods and analyses. Although the findings are preliminary, they have implications for clinicians' assessments of clients' emotional needs and characteristic presentations.
Management of severe aortic stenosis in the presence of an 8 mm right coronary stent protrusion
Authors: Novelli Alexandra , Gogo Prospero , Dauerman Harold L. , Polomsky Marek
Published: June 2024

Management of a protruding coronary stent into the aortic root in patients undergoing evaluation for transcatheter aortic valve replacement can be challenging. We describe a patient treated with stent trimming and surgical aortic valve replacement, highlighting the importance of a multidisciplinary evaluation and selection process in this complex scenario.
Subtelomeric microdeletion in chromosome 20p13 associated with short stature
Authors: Liu J. , Li Y. , Andersson H. C. , Upadia J.
Published: June 2024

Key Clinical Message

Among the total 10 reported cases with 20p13 microdeletion, including our patient, it is notable that 50% of patients presented a height below the 3rd percentile. We suggest that short stature is among the most common manifestations in patients with 20p13 subtelomeric microdeletion.

Chromosome 20p13 microdeletion occurs rarely, with only 10 reported cases. We report a 16‐year‐old male with a 1.59 Mb terminal deletion in chromosome 20p13, who presented with proportionate short stature, mild language delay, mild learning disability, and delayed puberty. The clinical phenotype associated with this deletion can exhibit clinical variability. Our patient deviates from the typical developmental and intellectual phenotype seen in the 20p13 deletion, instead displaying mild speech delay, short stature, and delayed puberty. The CSNK2A1 deletion, leading to haploinsufficiency, might be the potential mechanism. And the prominence of his proportionate short stature provides a unique perspective to review the existing literature.
Optimization of Batch Cooling Crystallization of Sodium Phosphite Through Genetic Algorithm
Authors: Wang Zechen , Rao Silin , Li Bao , Wang Jingtao
Published: June 2024

In this paper, the seeded batch cooling crystallization of sodium phosphite (SP) is simulated and optimized through a coupled method of the genetic algorithm and nonlinear programming. At first, the modeling and simulation test methods of the crystallization process are applied for the crystallization of SP, which expands the relevant study of SP from the experiment to the simulation. A comprehensive model is established in MATLAB/Simulink, and based on this model, the results of the common cooling strategy (linear cooling) on the process are investigated. Meanwhile, the process sensitivity to the change of seeding conditions is analyzed. Then, the coupled optimization method based on the genetic algorithm and nonlinear programming is applied to optimize the crystallization process for the first time, and the obtained optimized cooling strategy is compared to the result of the traditional nonlinear programming method (NLPM). The traditional NLPM has more significant effects on large seeding mass and small mean size, while the coupled method has better adaptability. When the coefficient of variation is almost fixed, the cooling strategy obtained by the coupled method could produce more crystals with large mean size. In addition, the end of the process can be reached earlier. The results show that the coupled method is more suitable for the optimization of the batch cooling crystallization of SP.
Dietary choline intake and its association with asthma: A study based on the National Health and Nutrition Examination Survey database
Authors: Shi Jiaqiang , Lin Yuming , Jiang Yingxiu , Qiu Guoguo , Jian Fanghua , Lin Wei , Zhang Shihao
Published: June 2024

Objective

This work endeavored to examine the correlation between dietary choline intake and the odds of asthma, utilizing data from the National Health and Nutrition Examination Survey (NHANES).

Methods

Aggregated data from seven cycles (2005–2018) in the NHANES database were utilized. The independent variable was dietary choline intake, and the dependent variable was asthma. The weighted logistic regression method was used to construct a model reflecting the relationship between these two factors. This work employed stratified analysis without adjusting for confounding factors and subgroup analysis with adjusted confounding factors to mine the association between dietary choline intake and asthma. Additionally, restricted cubic spline analysis examined nonlinear associations of the two in age subgroups.

Results

Forty five thousand and seven hundreds ninety seven samples were included here. The model indicating the relationship between dietary choline intake and asthma was constructed (OR: 0.86, 95% CI: 0.79–0.93, p < 0.001). Stratified analysis indicated that the interaction terms of age (p < 0.001) and body mass index (BMI) (p = 0.002) with dietary choline intake significantly influenced the relationship model. In the adjusted models, accounting for demographic characteristics, poverty impact ratio, BMI, exposure to environmental tobacco smoke, and total energy intake, an increase in dietary choline intake significantly reduced the odds of asthma (OR: 0.79, 95% CI: 0.72–0.88, p < 0.001). Subgroup analyses based on age and BMI revealed a significant negative correlation between dietary choline intake and the odds of asthma in the adult population (OR: 0.76, 95% CI: 0.67–0.86, p < 0.001), as well as in individuals with a BMI between 25 and 30 kg/m2 (OR: 0.79, 95% CI: 0.63–0.99, p = 0.042), and those with a BMI >30 kg/m2 (OR: 0.73, 95% CI: 0.60–0.89, p = 0.002).

Conclusion

Dietary choline intake was significantly inversely correlated with asthma prevalence, especially in adults and overweight/obese individuals, suggesting that increasing choline intake may reduce asthma risk. Further research is needed to explore this relationship and provide tailored dietary recommendations for different age and BMI groups to enhance asthma prevention and management.
Dispositional Empathy Among Psychotherapists: A Latent Profile Analysis
Authors: Lachance Valerie , Laverdière Olivier , Kealy David , Ogrodniczuk John S.
Published: June 2024

Objective

This study examined therapists' dispositional empathy profiles and how they differ based on professional and personal characteristics.

Method

A total of 376 clinicians was recruited for this study. Dispositional empathy was assessed with the Interpersonal Reactivity Index (IRI). Profiles were generated using latent profile analysis. Predictors of profiles were assessed with multiple self‐report questionnaires measuring demographic and professional characteristics, romantic attachment styles, five‐factor personality traits and vulnerable narcissism.

Results

A four‐profile solution was retained with the following proportions: rational empathic (20%), disengaged/detached (10%), empathic immersion (35%) and insecure/self‐absorbed (35%). Overall, few relationships were found regarding demographic and professional characteristics. In contrast, significant relationships were found between profile membership and personal characteristics, including avoidant and anxious attachment, agreeableness, conscientiousness, neuroticism, intellect/imagination and vulnerable narcissism.

Conclusion

The findings show that differences in therapists' empathic dispositions are linked to personality dimensions. Implications for psychotherapy research, practice and training are discussed.
Hot Exciton versus Hot Exciplex TADF Mechanism – Effect of the Donor‐Acceptor Functionalization Pattern on Anthracene‐based Emitters
Authors: Majer Felix , Roß Lars , Respondek A. Lennart , Bannwarth Christoph , Kuehne Alexander J. C.
Published: June 2024

Hot exciton emitters based on 9,10‐substituted anthracenes are a well‐investigated class of molecules featuring thermally activated delayed fluorescence (TADF). TADF converts triplet excitons into singlet excitons and improves the internal quantum efficiency of electroluminescent devices to performance beyond the limit of spin‐statistics of conventional emitters. In this paper, we compare different 1,8‐functionalized donor/acceptor‐substituted anthracenes and compare these to established 9,10‐functionalized hot exciton emitters. Interestingly, our new 1,8‐substituted anthracenes make use of a beneficial hot exciplex pathway, resulting in improved emission characteristics and higher photoluminescence quantum yield.
Ball‐Milling toward Nickel(II) Diphosphine Complexes for Direct Use in Catalysis
Authors: Pietras Natalia , Frąckowiak Dawid , Kownacki Ireneusz
Published: June 2024

Mechanochemistry turned out to be a powerful synthetic tool enabling the first efficient synthesis of nickel(II) complexes with diphosphines. It has been demonstrated that solventless ball‐milling of nickel(II) halides with diphosphines leads to the [NiX2(diphosphine)] type compounds, which can be directly used in catalysis without any purification. Moreover, it was confirmed that despite the presence of impurities in the resulting complexes, their catalytic activity remains identical to those obtained via traditional solvent‐based methods.
Stuttering in adolescence and the risk for dysglycemia in early adulthood
Authors: Rabotin Alexandra , Schwarz Yair , Pinhas‐Hamiel Orit , Amir Ofer , Derazne Estela , Tzur Dorit , Chodick Gabriel , Afek Arnon , Tsur Avishai M. , Twig Gilad
Published: June 2024

Aims

To investigate the association between stuttering during adolescence and the onset of dysglycemia (prediabetes or type 2 diabetes) in early adulthood among men and women.

Materials and Methods

This cohort study included Maccabi Health Services members assessed for mandatory military service at ages 16–19 during 1990–2019 and followed until 31 December 2020. Stuttering status was recorded in the baseline medical evaluation. Incident cases of dysglycemia were identified systematically using prediabetes and diabetes registries. Cox proportional hazard models were applied for men and women separately, adjusting for sociodemographics and medical status.

Results

The study cohort comprised 866,304 individuals (55% men; 0.21% with stuttering) followed for a total of 12,696,250 person‐years. During the study period, 7.6% (n = 36,603) of men and 9.0% (n = 34,723) of women were diagnosed with dysglycemia. The mean ages at diagnosis were 34 and 32 years for men and women, respectively. Women with stuttering exhibited the highest dysglycemia incidence rate (102.3 per 10,000 person‐years) compared with the other groups (61.4, 69.0, and 51.9 per 10,000 person‐years for women without stuttering, men with stuttering, and men without stuttering, respectively). For both men and women, those with stuttering showed an increased risk of being diagnosed with dysglycemia compared with those without (adjusted hazard ratios 1.18 [1.01–1.38] and 1.61 [1.15–2.26], respectively). The associations persisted in extensive sub‐analyses.

Conclusions

Stuttering in adolescence is associated with a higher risk of dysglycemia in early adulthood for men and women. Screening and targeted prevention in this population, especially women, may be beneficial.
Inferences about the population history of Rangifer tarandus from Y chromosome and mtDNA phylogenies
Authors: Bozlak Elif , Pokharel Kisun , Weldenegodguad Melak , Paasivaara Antti , Stammler Florian , Røed Knut H. , Kantanen Juha , Wallner Barbara
Published: June 2024

Reindeer, called caribou in North America, has a circumpolar distribution and all extant populations belong to the same species (Rangifer tarandus). It has survived the Holocene thanks to its immense adaptability and successful coexistence with humans in different forms of hunting and herding cultures. Here, we examine the paternal and maternal history of Rangifer based on robust Y‐chromosomal and mitochondrial DNA (mtDNA) trees representing Eurasian tundra reindeer, Finnish forest reindeer, Svalbard reindeer, Alaska tundra caribou, and woodland caribou. We first assembled Y‐chromosomal contigs, representing 1.3 Mb of single‐copy Y regions. Based on 545 Y‐chromosomal and 458 mtDNA SNPs defined in 55 males, maximum parsimony trees were created. We observed two well separated clades in both phylogenies: the “EuroBeringian clade” formed by animals from Arctic Islands, Eurasia, and a few from North America and the “North American clade” formed only by caribou from North America. The time calibrated Y tree revealed an expansion and dispersal of lineages across continents after the Last Glacial Maximum. We show for the first time unique paternal lineages in Svalbard reindeer and Finnish forest reindeer and reveal a circumscribed Y haplogroup in Fennoscandian tundra reindeer. The Y chromosome in domesticated reindeer is markedly diverse indicating that several male lineages have undergone domestication and less intensive selection on males. This study places R. tarandus onto the list of species with resolved Y and mtDNA phylogenies and builds the basis for studies of the distribution and origin of paternal and maternal lineages in the future.
Evaluation of flux and fate of plastic in terrestrial–aquatic–estuarine continuum by using an advanced process‐based model
Authors: Nakayama Tadanobu
Published: June 2024

Environmental contamination by plastics has been receiving considerable attention from scientists, policy makers and the public during the last few decades. Though some of the models have succeeded in simulating the transport and fate of plastic debris in freshwater systems, a complete model is now being developed to clarify the dynamic characteristics of the plastic budget on a continental scale. Recently, the author linked two process‐based eco‐hydrology models, NICE (National Integrated Catchment‐based Eco‐hydrology) and NICE‐BGC (BioGeochemical Cycle), to a plastic debris model that accounts for both the transport and fate of plastic debris (advection, dispersion, diffusion, settling, dissolution and biochemical degradation by light and temperature) and applied these models on a regional scale and also for global major rivers. The present study was newly modified to incorporate the plastic dynamics in estuaries by extending the previous studies. The model was employed to conduct a 2‐year global simulation aimed at evaluating changes in plastic dynamics in major rivers including 130 tidal estuaries. The model simulated the impact of estuaries on plastic budget and its seasonal variability caused by settling, resuspension and bedload transport during 2014–2015. The model showed that plastics with smaller particle sizes account for more in the water of estuaries than that of rivers, and plastics with larger particle sizes accumulate more on the riverbed. The simulated result also showed that estuaries trap more plastic than lakes and riverbeds (0.218 ± 0.053 Tg/year) although not as much as reservoirs (0.386 ± 0.103 Tg/year). More than 40% of plastics were retained by lakes, reservoirs, riverbeds and estuaries and the riverine plastic transport to the ocean was revised from 1.749 ± 0.371 Tg/year in the author's previous study to 1.000 ± 0.397 Tg/year in the present study. These results aid the development of solutions and measures for the reduction of plastic input to the ocean and help quantify the magnitude of plastic transport under climate change.
Measuring complexity for hierarchical models using effective degrees of freedom
Authors: Thorson James T.
Published: June 2024

Hierarchical models can express ecological dynamics using a combination of fixed and random effects, and measurement of their complexity (effective degrees of freedom, EDF) requires estimating how much random effects are shrunk toward a shared mean. Estimating EDF is helpful to (1) penalize complexity during model selection and (2) to improve understanding of model behavior. I applied the conditional Akaike Information Criterion (cAIC) to estimate EDF from the finite‐difference approximation to the gradient of model predictions with respect to each datum. I confirmed that this has similar behavior to widely used Bayesian criteria, and I illustrated ecological applications using three case studies. The first compared model parsimony with or without time‐varying parameters when predicting density‐dependent survival, where cAIC favors time‐varying demographic parameters more than conventional Akaike Information Criterion. The second estimates EDF in a phylogenetic structural equation model, and identifies a larger EDF when predicting longevity than mortality rates in fishes. The third compares EDF for a species distribution model fitted for 20 bird species and identifies those species requiring more model complexity. These highlight the ecological and statistical insight from comparing EDF among experimental units, models, and data partitions, using an approach that can be broadly adopted for nonlinear ecological models.
Evaluation dilemmas: Lessons learned in improving intervention outcomes and sustainability in Latin American communities
Authors: Zambrana Ruth Enid , Lovato Kristina , Burgos Nilsa
Published: June 2024

A significant number of studies on program evaluations in Latin America have limited, if any, information on procedures, impact, and sustainability. Scholarly work emphasizes how evaluation designs must be deeply cognizant of socioeconomic, ecological, and resource contexts to be effective. The purpose of this article is to bring together research findings from three types of knowledge centered on evaluation processes and practices for working within Latin American countries. A scan of the empirical literature, expert interviews, and a case study are triangulated to assess the barriers and impacts of program evaluations in economically disadvantaged Latin American countries. We conclude by describing long‐standing principles and guidelines for evaluation procedures to promote community engagement and human capital development in all evaluation collaborations. Lessons learned reinforce the tenets of culturally responsive evaluation (CRE) procedures as critical to reproduce interventions that improve the lives of communities. Equity, contextual knowledge, and equal partnership are driving forces in centering social problems and developing human capital and the betterment of community conditions in our partnering countries.
On the scientific credibility of paleoanthropology
Authors: Villmoare Brian , Kimbel William
Published: June 2024

Smith and Smith and Wood proposed that the human fossil record offers special challenges for causal hypotheses because “unique” adaptations resist the comparative method. We challenge their notions of “uniqueness” and offer a refutation of the idea that there is something epistemologically special about human prehistoric data. Although paleontological data may be sparse, there is nothing inherent about this information that prevents its use in the inductive or deductive process, nor in the generation and testing of scientific hypotheses. The imprecision of the fossil record is well‐understood, and such imprecision is often factored into hypotheses and methods. While we acknowledge some oversteps within the discipline, we also note that the history of paleoanthropology is clearly one of progress, with ideas tested and resolution added as data (fossils) are uncovered and new technologies applied, much like in sciences as diverse as astronomy, molecular genetics, and geology.
Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial)
Authors: Zeng Lijuan , Perin Jamie , Gross Alden L. , Shade David , Lanctôt Krista L. , Lerner Alan J. , Mintzer Jacobo E. , Brawman‐Mintzer Olga , Padala Prasad R. , van Dyck Christopher H. , Porsteinsson Anton P. , Craft Suzanne , Levey Allan , Herrmann Nathan , Rosenberg Paul B.
Published: June 2024

Objectives

To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia.

Methods

The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo‐controlled trial of MPH to treat apathy in individuals with apathy and AD. Participants in ADMET2 had vital signs and weight measured at monthly visits through 6 months. AEs, including insomnia, falls, and cardiovascular events, were reported at every visit by participants and families using a symptom checklist.

Results

The study included 98 participants in the MPH group and 101 in the placebo group. Participants in the MPH group experienced greater weight loss on average than the placebo through the 6‐month follow‐up, with a difference in change between MPH and placebo of 2.8 lb (95% confidence interval, CI: 0.7, 4.9 lb). No treatment group differences in change during the trial were found in systolic and diastolic blood pressure. More participants in the MPH group reported falls during the follow‐up, 10 versus 6 in MPH and placebo groups, respectively. No differences in post‐baseline insomnia were observed between the treatment groups. No participants reported instances of myocardial infarction, congestive heart failure, arrhythmia, stroke, or cardiomyopathy throughout the study period.

Conclusions

MPH use in AD patients for treating apathy is relatively safe, particularly notable given the many medical comorbidities in this population. There was a statistically significant but modest weight loss associated with MPH use, and clinicians are thus advised to monitor weight during MPH treatment.
Hypermethylation of GSTM5 and its effect on oxidation in myelodysplastic syndrome
Authors: Wang Chi , Yu Yafei , Chang Qing , Dong Tengteng , Wang Liye , Li Mianyang
Published: June 2024

Background

Hypermethylation of glutathione‐S‐transferase 5 (GSTM5) and its effect on oxidation in the pathogenesis of myelodysplastic syndrome (MDS) were investigated.

Methods

GSTM5 methylation was detected in bone marrow (BM) samples from MDS patients, acute myeloid leukemia (AML) patients, and control individuals using methylation‐specific PCR and MassARRAY analysis. Bisulfite sequencing PCR was performed to verify methylation levels, while mRNA levels were determined using reverse transcription polymerase chain reaction. Correlations between GSTM5 methylation and clinical parameters were analyzed. The MDS cell line, SKM‐1, was treated with decitabine, buthionine sulfoximine, or overexpression of GSTM5, and the glutathione level and cell viability were detected.

Results

The MassARRAY analysis revealed significant differences in GSTM5 methylation levels between the MDS and control groups. GSTM5 methylation levels were significantly increased in the high‐risk subgroup and showed a significant association with MDS progression to AML (hazard ratio = 3.6). Levels of GSTM5 mRNA were significantly decreased in the MDS group, exhibiting a negative correlation with the GSTM5 gene methylation level. Normal BM HS‐5 cells exhibited significantly lower levels of GSTM5 methylation than SKM‐1 cells. Overexpression of GSTM5 in SKM‐1 cells or treatment with buthionine sulfoximine or decitabine resulted in inhibition of proliferation and significantly decreased glutathione levels.

Conclusions

GSTM5 plays an anti‐oxidative role in MDS and the tumor suppressor effect of GSTM5 may be mediated by reducing glutathione levels. GSTM5 hypermethylation and low levels of GSTM5 expression may be prognostic markers for MDS.
AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases
Authors: Yu Yuan , Wang Shuqing , Wang Yaqi , Zhang Qianyi , Zhao Lina , Wang Yang , Wu Jinghua , Han Liyuan , Wang Junli , Guo Jimin , Xue Jiarui , Dong Fenglin , Zhang Jing Hua , Zhang Liu , Liu Yan , Shi Guogang , Zhang Xiaojun , Li Yufeng , Li Jingwu
Published: June 2024

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT‐mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull‐down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2‐[1,2‐3H]‐deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1‐mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1‐S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.
A novel interplay between PRC2 and miR‐3189 regulates epithelial–mesenchymal transition (EMT) via modulating COL6A2 in glioblastoma
Authors: Sharma Vikas , Vinchure Omkar Suhas , Yadav Garima , Sarkar Chitra , Kulshreshtha Ritu
Published: June 2024

Recent studies have shed light on disrupted collagen signaling in Gliomas, yet the regulatory landscape remains largely unexplored. This study enquired into the role of polycomb repressive complex‐2 (PRC2)‐mediated H3K27me3 modification, a key epigenetic factor in glioma. Using in‐house data, we identified miRNAs downregulated in glioblastoma (GBM) with the potential to regulate Collagen VI family genes. Notably, miR‐3189 emerged as a prime PRC2 target. Its expression was significantly downregulated in Indian GBM patients as well as other glioma cohorts. Mechanistic insights, involving Luciferase assays, mutagenesis, and Western blot analysis, confirmed direct targeting of Collagen VI member COL6A2 by miR‐3189‐3p. Functional assays demonstrated that miR‐3189‐3p restrained GBM malignancy by inhibiting proliferation, migration, and epithelial–mesenchymal transition (EMT). Conversely, COL6A2 overexpressed in GBM patients, countered miR‐3189, and promoted the malignant phenotype. Gene set enrichment analysis highlighted EMT enrichment in GBM patients with elevated COL6A2 expression, carrying prognostic implications. This study uncovers intricate interactions between two epigenetic regulators—H3K27me3 and miR‐3189—working synergistically to modulate Collagen VI gene; thus, influencing the malignancy of GBM. Targeting this H3K27me3|miR‐3189‐3p|COL6A2 axis presents a potential therapeutic avenue against GBM.
Short‐term mortality prediction in acute pulmonary embolism: Radiomics values of skeletal muscle and intramuscular adipose tissue
Authors: Shahzadi Iram , Zwanenburg Alex , Frohwein Lynn Johann , Schramm Dominik , Meyer Hans Jonas , Hinnerichs Mattes , Moenninghoff Christoph , Niehoff Julius Henning , Kroeger Jan Robert , Borggrefe Jan , Surov Alexey
Published: June 2024

Background

Acute pulmonary embolism (APE) is a potentially life‐threatening disorder, emphasizing the importance of accurate risk stratification and survival prognosis. The exploration of imaging biomarkers that can reflect patient survival holds the potential to further enhance the stratification of APE patients, enabling personalized treatment and early intervention. Therefore, in this study, we develop computed tomography pulmonary angiography (CTPA) radiomic signatures for the prognosis of 7‐ and 30‐day all‐cause mortality in patients with APE.

Methods

Diagnostic CTPA images from 829 patients with APE were collected. Two hundred thirty‐four features from each skeletal muscle (SM), intramuscular adipose tissue (IMAT) and both tissues combined (SM + IMAT) were calculated at the level of thoracic vertebra 12. Radiomic signatures were derived using 10 times repeated three‐fold cross‐validation on the training data for SM, IMAT and SM + IMAT for predicting 7‐ and 30‐day mortality independently. The performance of the radiomic signatures was then evaluated on held‐out test data and compared with the simplified pulmonary embolism severity index (sPESI) score, a well‐established biomarker for risk stratification in APE. Predictive accuracy was assessed by the area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI), sensitivity and specificity.

Results

The radiomic signatures based on IMAT and a combination of SM and IMAT (SM + IMAT) achieved moderate performance for the prediction of 30‐day mortality on test data (IMAT: AUC = 0.68, 95% CI [0.57–0.78], sensitivity = 0.57, specificity = 0.73; SM + IMAT: AUC = 0.70, 95% CI [0.60–0.79], sensitivity = 0.74, specificity = 0.54). Radiomic signatures developed for predicting 7‐day all‐cause mortality showed overall low performance. The clinical signature, that is, sPESI, achieved slightly better performance in terms of AUC on test data compared with the radiomic signatures for the prediction of both 7‐ and 30‐day mortality on the test data (7 days: AUC = 0.73, 95% CI [0.67–0.79], sensitivity = 0.92, specificity = 0.16; 30 days: AUC = 0.74, 95% CI [0.66–0.82], sensitivity = 0.97, specificity = 0.16).

Conclusions

We developed and tested radiomic signatures for predicting 7‐ and 30‐day all‐cause mortality in APE using a multicentric retrospective dataset. The present multicentre work shows that radiomics parameters extracted from SM and IMAT can predict 30‐day all‐cause mortality in patients with APE.
Experimental investigation and thermomechanical performance evaluation of supercritical water oxidation of n‐dodecane/tributyl phosphate
Authors: Mi Zhaoxia , Wang Shuzhong , Sun Shenghan , Li Yanhui , Zhang Fan , Duan Yuanwang
Published: June 2024

BACKGROUND

Nuclear energy has brought immense benefits while also generating a large amount of wastewater that urgently needs to be processed. Supercritical water oxidation (SCWO) technology serves as an efficient method for wastewater treatment. In this study, a SCWO experiment was carried out with organic solvent of 30% tributyl phosphate (TBP) and 70% n‐dodecane. This study investigated the operating parameters and the effects of enhanced oxidation techniques on chemical oxygen demand (COD) removal efficiency. An organic solvent SCWO process was developed, and its energy and exergy efficiencies were assessed using Aspen Plus.

RESULTS

The COD removal was about 96.18% at the experimental parameters of 500 °C, 10 min, 25 MPa, oxidation coefficient of 1.5 and material concentration of 4 wt%. COD removal increased by 3.09% with the addition of CeO2. Finally, the overall energy and exergy efficiencies of the SCWO system were found to be 58.8% and 9.1% respectively by Aspen Plus.

CONCLUSION

It was found that the reaction temperature had the greatest effect on the COD removal rate compared with other reaction parameters. The decomposition of organic solvents can be divided into two stages, fast and slow, and the addition of alkali and catalyst can effectively promote the decomposition of waste organic solvents. The experiments showed that SCWO is feasible for the treatment of n‐dodecane/TBP. © 2024 Society of Chemical Industry (SCI).
Electrical impedance detects early stages of bone healing: An in vivo explanatory study of tibial fractures in rabbits
Authors: Frost Markus Winther , Tirta Maria , Rahbek Ole , Rytoft Laura Amalie , Ding Ming , Shen Ming , Duch Kirsten , Kold Søren
Published: June 2024

Purpose

Healing after bone fracture is assessed by clinical examination and frequent radiographs, which expose patients to radiation and lack standardisation. This study aimed to explore electrical impedance patterns during bone healing using electrical impedance spectroscopy in 18 rabbits subjected to tibial fracture stabilised with an external fixator.

Methods

Impedance was measured daily across the fracture site at a frequency range of 5 Hz to 1 MHz. Biweekly radiographs were analysed using modified anterior‐posterior (AP) radiographic union score of the tibia (RUST). The animals were divided into three groups with different follow‐up times: 1, 3 and 6 weeks for micro‐computer tomography and mechanical testing.

Results

A decreasing trend in impedance was observed over time for all rabbits at lower frequencies. Impedance closest to 5 Hz showed a statistically significant decrease over time, with greatest decrease occurring during the first 7 postoperative days. At 5 Hz, a statistically significant correlation was found between impedance and the modified AP RUST score and between impedance and bone volume fraction.

Conclusions

This study showed that the electrical impedance can be measured in vivo at a distance from the fracture site with a consistent change in impedance over time and revealed significant correlation between increasing radiographic union score and decreasing impedance.

Level of Evidence

Not applicable.
Item‐reduced Forgotten Joint Score provides adequate psychometric properties in ACLR patients
Authors: Kekki Carolina , Wörner Tobias , Stålman Anders , von Essen Christoffer
Published: June 2024

Purpose

The purpose of this study was to evaluate content validity, test–retest reliability, internal consistency, construct validity, responsiveness and floor/ceiling effects of Forgotten Joint Score (FJS) for assessing functions in activities of daily living (ADL) following anterior cruciate ligament reconstruction (ACLR) and perform an item reduction of FJS.

Methods

Swedish‐speaking ACLR patients in one surgical clinic were eligible. Content validity was evaluated through patient responses and patient and expert clinician relevance ratings, omitting items with low relevance. Principal component factor analysis, Cronbach's ⍺, paired t test, correlations between FJS and Knee Injury and Osteoarthritis Outcome Score (KOOS), Cohen's d effect sizes (ESs) and standardized response mean (SRM) were used to evaluate internal consistency, test–retest reliability, construct validity and responsiveness. Floor/ceiling effects were calculated. FJS was expected to reveal one dominant factor, a Cronbach's ⍺ between 0.70 and 0.95, correlations >0.50 to all KOOS subscores, highest for ADL, moderate ES and SRM, floor/ceiling effects <15%.

Results

One hundred and seventy‐six participants (103 for assessing internal consistency, construct validity, responsiveness and floor/ceiling effects; 73 for assessing test–retest reliability and content validity) were included. Item reduction yielded a nine‐item FJS (FJS‐9). FJS‐12 and FJS‐9 demonstrated sufficient content validity (95% confidence interval [CI], 2.5–3.1, respectively, 2.9–3.3). FJS‐9 was found unidimensional, and FJS‐12 was multidimensional. Cronbach's ⍺ was 0.94 for FJS, and the intraclass correlation coefficient > 0.90. FJS showed significant correlations >0.65 to all KOOS subscales, moderate ES and SRM > 0.50. No floor/ceiling effects were found.

Conclusion

FJS‐9 demonstrated adequate validity for the evaluation of joint awareness in ACLR patients and can be a valuable tool to assess ADL and joint awareness.

Level of Eidence

Level III.
Burnout among the podiatry profession: A survey of podiatrists in Aotearoa New Zealand
Authors: Clarke Mia , Frecklington Mike , Stewart Sarah
Published: June 2024

Introduction

Burnout and occupational stress have not yet been explored within the Aotearoa New Zealand (AoNZ) podiatry workforce despite research suggesting an increased risk among this population. This study aimed to: (i) determine the prevalence and severity of burnout risk and occupational stress among AoNZ podiatrists; (ii) determine the factors associated with burnout risk and occupational stress among AoNZ podiatrists; and (iii) examine the relationship between burnout risk and occupational stress.

Methods

A cross‐sectional online survey study was undertaken involving registered podiatrists practicing in AoNZ. Personal and professional demographic characteristics were captured. Participants also completed the Maslach Burnout Inventory (assessing three domains of emotional exhaustion, depersonalisation and personal accomplishment) and the Workplace Stress Scale as measures of burnout risk and occupational stress, respectively. Descriptive statistics, multiple regression analyses and correlation analyses were performed to address the research aims.

Results

Responses from 112 AoNZ podiatrists were included in the analyses. High levels of emotional exhaustion were identified in 43.8% of practitioners and were associated with physical activity status, sector of work, working in isolation and work hours (R2 = 0.304, F (8, N = 110) = 5.519, p < 0.001). High levels of depersonalisation were seen in 13.4% of practitioners and were associated with patient caseload and work hours, (R2 = 0.183, F (4, N = 108) = 5.770, p < 0.001). Low levels of personal accomplishment were observed in 8.9% of practitioners and associated with ethnicity, physical activity status and patient caseload, (R2 = 0.152, F (5, N = 106) = 3.577, p < 0.005). A total of 27.7% of practitioners exhibited an overall moderate to high risk of developing burnout. Over a fifth of practitioners exhibited stress at severe or dangerous levels. Stress levels were significantly associated with physical activity status, sector of work and management responsibility, (R2 = 0.282, F (5, N = 47) = 3.218, p = 0.15). A strong positive relationship was found between emotional exhaustion and stress (rho = 0.59, p < 0.001).

Conclusions

The findings reflect a moderate to severe risk of developing burnout within the workforce, with high workloads and collegial isolation constituting the primary modifiable factors driving burnout development. To maintain retention and well‐being within the workforce, mitigation strategies must be implemented to address this issue.
Interleukin‐17A educated hepatic stellate cells promote hepatocellular carcinoma occurrence through fibroblast activation protein expression
Authors: Ni Jun‐Sheng , Fu Si‐Yuan , Wang Zong‐Yan , Ding Wen‐Bin , Huang Jian , Guo Xing‐Gang , Gu Fang‐Ming
Published: June 2024

Background

Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin‐17A (IL‐17A), a pivotal pro‐inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL‐17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL‐17A and HSCs in the context of HCC.

Methods

An HCC model was established in male Sprague–Dawley rats using diethylnitrosamine to explore the roles of IL‐17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno‐associated virus. A suite of molecular techniques, including RT‐qPCR, enzyme‐linked immunosorbent assays, Western blotting, cell counting kit‐8 assays and colony formation assays, was employed for in vitro analyses.

Results

The study findings indicate that IL‐17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro‐tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL‐17A‐induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL‐17A‐stimulated HSCs was observed to reverse the HCC‐promoting effects of HSCs.

Conclusions

The collective evidence from this study implicates the IL‐17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL‐17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.