bluuebunny/crossref_metadata_2025 huggingface dataset:
On How to Develop Emotion Taxonomies
Authors: Majeed Raamy
Published: June 2024

How should we go about developing emotion taxonomies suitable for a science of emotion? Scientific categories are supposed to be “projectable”: They must support generalizations required for the scientific practices of induction and explanation. Attempts to provide projectable emotion categories typically classify emotions in terms of a limited set of modules, but such taxonomies have had limited uptake because they arguably misrepresent the diversity of our emotional repertoire. However, more inclusive, non-modular, taxonomies also prove problematic, for they struggle to meet the projectability constraint. In this paper, I explain how a developmental approach to emotion, one that utilizes the notion of progressive modularization, can help us approach emotion categorization in a more inclusive and projectable manner.
Fatal Hemoperitoneum Secondary to a Spontaneous Splenic Vein Rupture
Authors: Fleury Luther , McEnnan Carolina
Published: June 2024

Spontaneous hemoperitoneum is rare and is often labeled as idiopathic because the source of bleeding is never found. We report the case of a 35-year-old male who died of a splenic vein rupture. The decedent was a chronic alcoholic with a reported history of cirrhosis and medication noncompliance. Internal examination revealed pale visceral organs, marked hemoperitoneum, a fibrotic/nodular liver, esophageal varices, and a ruptured splenic vein. Pertinent microscopic findings include liver parenchyma with bridging fibrous septa, nodules of regenerating hepatocytes, and the presence of Mallory-Denk bodies. The immediate cause of death was determined to be splenic vein rupture with the underlying cause of death being chronic alcoholism. This case is reported to emphasize the importance of correlating past medical history with thorough vascular dissection in cases of spontaneous hemoperitoneum. In a patient with fatal hemoperitoneum and risk factors for splenic vein pathology (ie, cirrhosis, portal vein hypertension), a high suspicion should be kept for splenic vein rupture.
Wearable biosensors for human health: A bibliometric analysis from 2007 to 2022
Authors: Muñoz-Urtubia Nicolás , Vega-Muñoz Alejandro , Estrada-Muñoz Carla , Salazar-Sepúlveda Guido , Contreras-Barraza Nicolás , Salinas-Martínez Nicolás , Méndez-Celis Paula , Carmelo-Adsuar José
Published: June 2024

Objective

This study aimed to determine the status of scientific production on biosensor usage for human health monitoring.

Methods

We used bibliometrics based on the data and metadata retrieved from the Web of Science between 2007 and 2022. Articles unrelated to health and medicine were excluded. The databases were processed using the VOSviewer software and auxiliary spreadsheets. Data extraction yielded 275 articles published in 161 journals, mainly concentrated on 13 journals and 881 keywords plus.

Results

The keywords plus of high occurrences were estimated at 27, with seven to 30 occurrences. From the 1595 identified authors, 125 were consistently connected in the coauthorship network in the total set and were grouped into nine clusters. Using Lotka's law, we identified 24 prolific authors, and Hirsch index analysis revealed that 45 articles were cited more than 45 times. Crosses were identified between 17 articles in the Hirsch index and 17 prolific authors, highlighting the presence of a large set of prolific authors from various interconnected clusters, a triad, and a solitary prolific author.

Conclusion

An exponential trend was observed in biosensor research for health monitoring, identifying areas of innovation, collaboration, and technological challenges that can guide future research on this topic.
Mapping Racial and Ethnic Variation in Climate Belief Networks
Authors: Stewart Evan , Rivera-Kientz Katsyris , Dacey Timothy
Published: June 2024

Past research observing differences in environmental attitudes across racial and ethnic groups often mischaracterized those differences as deficits, casting environmental concern as a predominately White issue. Our study contributes to current work correcting this account by mapping substantive differences in the structure of climate attitudes across racial and ethnic groups. We use belief network analysis on 14 years of survey data from the Climate Change in the American Mind (CCAM) survey ( n = 20,396), and we find substantive differences in the climate belief networks of White, Black, and Hispanic survey respondents. These differences are not primarily about the strength or weakness of associations between attitudes, as theorized by deficit accounts. Instead, we find different attitudes are most central to these respective belief networks. We argue research on the social construction of race and ethnicity can better measure substantive variation in climate attitudes among Black, Indigenous, and People of Color (BIPOC) respondents by attending to how racialized experiences with climate change may produce aggregated belief networks with different profiles of salient issues and different interpretive frameworks.
Autistic pupils’ experiences in primary and post-primary schools: A scoping review and consultation with autistic pupils in Ireland
Authors: Lynam Aoife , Sweeney Mary Rose , Keenan Lisa , McNally Sinéad
Published: June 2024

Background and aims

Autistic pupils have the right to be heard in matters concerning their education and to be active agents in shaping their school experiences. Despite this, educational policies and research have rarely included the voices of autistic children, failing to identify what they consider to be beneficial and meaningful in their own education. This study aimed to (i) summarise existing literature exploring autistic pupils’ experiences at school from their own perspectives and (ii) identify gaps for future research through a consultation with autistic pupils.

Methods

A scoping review was conducted to identify studies exploring first-person accounts of autistic pupils’ school experiences (primary and secondary; aged 4–18 years) published between 2005 and 2023. Thematic analysis was conducted to identify overarching thematic categories across the included studies. Review findings were discussed through a consultation with a Child and Youth Advisory Group (CYAG) comprised of autistic pupils in Ireland ( N = 3), to seek feedback and inform a future research agenda.

Main contribution

Thirty-six studies were included in the review and six themes were identified: Experiences of feeling misunderstood, of bullying and masking, of feeling excluded, of anxiety, of sensory needs in school, and of being overwhelmed during transitions. Consultation with the CYAG highlighted that these six themes were consistent with autistic pupils’ experiences but that reports of positive experiences were missing in the literature.

Conclusions

This study identified several gaps in the literature on the school experiences of autistic pupils, based on both the scoping review and consultation with the CYAG. While the CYAG validated the themes identified in existing literature, there is a need for greater diversity in the samples included and increased focus on the potential positive aspects of the school experience. Implications. These findings have important research implications. In particular, further studies are needed with autistic pupils at primary school level, including those who are minimally or non-speaking, as well as ensuring pupils with positive school experiences are also represented. Findings also highlight the need for continued collaboration with autistic pupils themselves in matters concerning their education.
Humanitarian border: Reprise. Anti-human trafficking discourses and security practices at the southern Italian border
Authors: Anderlini Jacopo
Published: June 2024

The article analyses the friction between anti-human trafficking discourse and border practices in the context of EU migration management: the narrative of protecting migrants from human traffickers, evoked by law enforcement actors, merges with a discourse criminalizing migration, discerning between the migrant as a passive victim – the asylum seeker –the “economic migrant” and the ruthless smuggler. Practices and procedures at the border aim primarily at classifying migrants within these categories, in fact identifying potentially dangerous subjects for the country of arrival. The case study is the Southern European border in Sicily, and the operations enacted by law enforcement actors and EU agencies within the hotspot facilities. Moving from the ethnographic fieldwork I conducted on this context since 2016, witnessing disembarkations and border procedures and getting access to the hotspot structures of Lampedusa and Pozzallo in 2021, the article analyses the transformation of the border apparatus and of contemporary governance of mobility. What delineates is a revival of the humanitarian border, where anti-human trafficking discourses are evoked to legitimize exclusionary border procedures and practices.
Genomic analyses of withers height and linear conformation traits in German Warmblood horses using imputed sequence-level genotypes
Authors: Reich Paula , Möller Sandra , Stock Kathrin F. , Nolte Wietje , von Depka Prondzinski Mario , Reents Reinhard , Kalm Ernst , Kühn Christa , Thaller Georg , Falker-Gieske Clemens , Tetens Jens
Published: June 2024

Background

Body conformation, including withers height, is a major selection criterion in horse breeding and is associated with other important traits, such as health and performance. However, little is known about the genomic background of equine conformation. Therefore, the aim of this study was to use imputed sequence-level genotypes from up to 4891 German Warmblood horses to identify genomic regions associated with withers height and linear conformation traits. Furthermore, the traits were genetically characterised and putative causal variants for withers height were detected.

Results

A genome-wide association study (GWAS) for withers height confirmed the presence of a previously known quantitative trait locus (QTL) on Equus caballus (ECA) chromosome 3 close to the LCORL/NCAPG locus, which explained 16% of the phenotypic variance for withers height. An additional significant association signal was detected on ECA1. Further investigations of the region on ECA3 identified a few promising candidate causal variants for withers height, including a nonsense mutation in the coding sequence of the LCORL gene. The estimated heritability for withers height was 0.53 and ranged from 0 to 0.34 for the conformation traits. GWAS identified significantly associated variants for more than half of the investigated conformation traits, among which 13 showed a peak on ECA3 in the same region as withers height. Genetic parameter estimation revealed high genetic correlations between these traits and withers height for the QTL on ECA3.

Conclusions

The use of imputed sequence-level genotypes from a large study cohort led to the discovery of novel QTL associated with conformation traits in German Warmblood horses. The results indicate the high relevance of the QTL on ECA3 for various conformation traits, including withers height, and contribute to deciphering causal mutations for body size in horses.
Revealing critical mechanisms in determining sorghum resistance to drought and salt using mRNA, small RNA and degradome sequencing
Authors: Li Qiong , Wang Jibin , Liu Qian , Zhang Junhan , Zhu Xinlei , Hua Yinpeng , Zhou Ting , Yan Songxian
Published: June 2024

Background

Plant growth and development are severely threatened by drought and salt stresses. Compared with structural genes, transcription factors (TFs) play more pivotal roles in plant growth and stress adaptation. However, the underlying mechanisms of sorghum adapting to drought and salt are insufficient, and systematic analysis of TFs in response to the above stresses is lacking.

Results

In this study, TFs were identified in sorghum and model plants (Arabidopsis thaliana and rice), and gene number and conserved domain were compared between sorghum and model plants. According to syntenic analysis, the expansion of sorghum and rice TFs may be due to whole-genome duplications. Between sorghum and model plants TFs, specific conserved domains were identified and they may be related to functional diversification of TFs. Forty-five key genes in sorghum, including four TFs, were likely responsible for drought adaption based on differently expression analysis. MiR5072 and its target gene (Sobic.001G449600) may refer to the determination of sorghum drought resistance according to small RNA and degradome analysis. Six genes were associated with drought adaptation of sorghum based on weighted gene co-expression network analysis (WGCNA). Similarly, the core genes in response to salt were also characterized using the above methods. Finally, 15 candidate genes, particularly two TFs (Sobic.004G300300, HD-ZIP; Sobic.003G244100, bZIP), involved in combined drought and salt resistance of sorghum were identified.

Conclusions

In summary, the findings in this study help clarify the molecular mechanisms of sorghum responding to drought and salt. We identified candidate genes and provide important genetic resource for potential development of drought-tolerant and salt-tolerant sorghum plants.
Using machine learning to develop preoperative model for lymph node metastasis in patients with bladder urothelial carcinoma
Authors: Ji Junjie , Zhang Tianwei , Zhu Ling , Yao Yu , Mei Jingchang , Sun Lijiang , Zhang Guiming
Published: June 2024

Background

Lymph node metastasis (LNM) is associated with worse prognosis in bladder urothelial carcinoma (BUC) patients. This study aimed to develop and validate machine learning (ML) models to preoperatively predict LNM in BUC patients treated with radical cystectomy (RC).

Methods

We retrospectively collected demographic, pathological, imaging, and laboratory information of BUC patients who underwent RC and bilateral lymphadenectomy in our institution. Patients were randomly categorized into training set and testing set. Five ML algorithms were utilized to establish prediction models. The performance of each model was assessed by the area under the receiver operating characteristic curve (AUC) and accuracy. Finally, we calculated the corresponding variable coefficients based on the optimal model to reveal the contribution of each variable to LNM.

Results

A total of 524 and 131 BUC patients were finally enrolled into training set and testing set, respectively. We identified that the support vector machine (SVM) model had the best prediction ability with an AUC of 0.934 (95% confidence interval [CI]: 0.903–0.964) and accuracy of 0.916 in the training set, and an AUC of 0.855 (95%CI: 0.777–0.933) and accuracy of 0.809 in the testing set. The SVM model contained 14 predictors, and positive lymph node in imaging contributed the most to the prediction of LNM in BUC patients.

Conclusions

We developed and validated the ML models to preoperatively predict LNM in BUC patients treated with RC, and identified that the SVM model with 14 variables had the best performance and high levels of clinical applicability.
Air pollutants, seasonal influenza, and acute otitis media in children: a population-based analysis using 22-year hospitalization data
Authors: Li Conglu , Jiang Xiaoting , Wei Yuchen , Wang Yawen , Lao Xiangqian , Yue Qianying , Chong Ka Chun
Published: June 2024

Background

Acute otitis media (AOM) is a prevalent childhood acute illness, with 13.6 million pediatric office visits annually, often stemming from upper respiratory tract infections (URI) and affected by environmental factors like air pollution and cold seasons.

Methods

Herein, we made use of territory-wide hospitalization data to investigate the relationships between meteorological factors, air pollutants, influenza infection, and AOM for children observed from 1998 to 2019 in Hong Kong. Quasi-Poisson generalized additive model, combined with a distributed-lag non-linear model, was employed to examine the relationship between weekly AOM admissions in children and weekly influenza-like illness-positive (ILI +) rates, as well as air pollutants (i.e., oxidant gases, sulfur dioxide, and fine particulate matter), while accounting for meteorological variations.

Results

There were 21,224 hospital admissions due to AOM for children aged ≤ 15 years throughout a 22-year period. The cumulative adjusted relative risks (ARR) of AOM were 1.15 (95% CI, 1.04–1.28) and 1.07 (95% CI, 0.97–1.18) at the 95th percentile concentration of oxidant gases (65.9 ppm) and fine particulate matter (62.2 μg/m3) respectively, with reference set to their medians of concentration. The ARRs exhibited a monotone increasing trend for all-type and type-specific ILI + rates. Setting the reference to zero, the cumulative ARRs of AOM rose to 1.42 (95% CI, 1.29–1.56) at the 95th percentile of ILI + Total rate, and to 1.07 (95% CI, 1.01–1.14), 1.19 (95% CI, 1.11–1.27), and 1.22 (95% CI, 1.13–1.32) for ILI + A/H1N1, A/H3N2, and B, respectively.

Conclusions

Our findings suggested that policy on air pollution control and influenza vaccination for children need to be implemented, which might have significant implications for preventing AOM in children.
Effectiveness of home treatment in children and adolescents with psychiatric disorders—systematic review and meta-analysis
Authors: Graf Daniel , Sigrist Christine , Boege Isabel , Cavelti Marialuisa , Koenig Julian , Kaess Michael
Published: June 2024

Background

Home treatment in child and adolescent psychiatry offers an alternative to conventional inpatient treatment by involving the patient’s family, school, and peers more directly in therapy. Although several reviews have summarised existing home treatment programmes, evidence of their effectiveness remains limited and data synthesis is lacking.

Methods

We conducted a meta-analysis on the effectiveness of home treatment compared with inpatient treatment in child and adolescent psychiatry, based on a systematic search of four databases (PubMed, CINAHL, PsychINFO, Embase). Primary outcomes were psychosocial functioning and psychopathology. Additional outcomes included treatment satisfaction, duration, costs, and readmission rates. Group differences were expressed as standardised mean differences (SMD) in change scores. We used three-level random-effects meta-analysis and meta-regression and conducted both superiority and non-inferiority testing.

Results

We included 30 studies from 13 non-overlapping samples, providing data from 1795 individuals (mean age: 11.95 ± 2.33 years; 42.5% female). We found no significant differences between home and inpatient treatment for postline psychosocial functioning (SMD = 0.05 [− 0.18; 0.30], p = 0.68, I2 = 98.0%) and psychopathology (SMD = 0.10 [− 0.17; 0.37], p = 0.44, I2 = 98.3%). Similar results were observed from follow-up data and non-inferiority testing. Meta-regression showed better outcomes for patient groups with higher levels of psychopathology at baseline and favoured home treatment over inpatient treatment when only randomised controlled trials were considered.

Conclusions

This meta-analysis found no evidence that home treatment is less effective than conventional inpatient treatment, highlighting its potential as an effective alternative in child and adolescent psychiatry. The generalisability of these findings is reduced by limitations in the existing literature, and further research is needed to better understand which patients benefit most from home treatment.

Trial registration

Registered at PROSPERO (CRD42020177558), July 5, 2020.
DUSP5 regulated by YTHDF1-mediated m6A modification promotes epithelial-mesenchymal transition and EGFR-TKI resistance via the TGF-β/Smad signaling pathway in lung adenocarcinoma
Authors: Fan Weina , Xing Ying , Yan Shi , Liu Wei , Ning Jinfeng , Tian Fanglin , Wang Xin , Zhan Yuning , Luo Lixin , Cao Mengru , Huang Jian , Cai Li
Published: June 2024

Background

Lung adenocarcinoma (LUAD) patients have a dismal survival rate because of cancer metastasis and drug resistance. The study aims to identify the genes that concurrently modulate EMT, metastasis and EGFR-TKI resistance, and to investigate the underlying regulatory mechanisms.

Methods

Cox regression and Kaplan–Meier analyses were applied to identify prognostic oncogenes in LUAD. Gene set enrichment analysis (GSEA) was used to indicate the biological functions of the gene. Wound-healing and Transwell assays were used to detect migratory and invasive ability. EGFR-TKI sensitivity was evaluated by assessing the proliferation, clonogenic survival and metastatic capability of cancer cells with treatment with gefitinib. Methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) analyses established the level of m6A modification present on the target gene and the protein’s capability to interact with RNA, respectively. Single-sample gene set enrichment (ssGSEA) algorithm used to investigate levels of immune cell infiltration.

Results

Our study identified dual-specificity phosphatase 5 (DUSP5) as a novel and powerful predictor of adverse outcomes for LUAD by using public datasets. Functional enrichment analysis found that DUSP5 was positively enriched in EMT and transforming growth factor-beta (TGF-β) signaling pathway, a prevailing pathway involved in the induction of EMT. As expected, DUSP5 knockdown suppressed EMT via inhibiting the canonical TGF-β/Smad signaling pathway in in vitro experiments. Consistently, knockdown of DUSP5 was first found to inhibit migratory ability and invasiveness of LUAD cells in in vitro and prevent lung metastasis in in vivo. DUSP5 knockdown re-sensitized gefitinib-resistant LUAD cells to gefitinib, accompanying reversion of EMT progress. In LUAD tissue samples, we found 14 cytosine-phosphate-guanine (CpG) sites of DUSP5 that were negatively associated with DUSP5 gene expression. Importantly, 5′Azacytidine (AZA), an FDA-approved DNA methyltransferase inhibitor, restored DUSP5 expression. Moreover, RIP experiments confirmed that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a m6A reader protein, could bind DUSP5 mRNA. YTHDF1 promoted DUSP5 expression and the malignant phenotype of LUAD cells. In addition, the DUSP5-derived genomic model revealed the two clusters with distinguishable immune features and tumor mutational burden (TMB).

Conclusions

Briefly, our study discovered DUSP5 which was regulated by epigenetic modification, might be a potential therapeutic target, especially in LUAD patients with acquired EGFR-TKI resistance.

Graphical Abstract
The modern-day “Rest Cure”: “The yellow Wallpaper” and underrepresentation in clinical research
Authors: Villar Camille Francesca
Published: June 2024

Gothic literature—a genre brimming with madness, supernaturalism, and psychological terror—offers innumerable case studies potentially representing how psychiatric patients perceive their treatment from healthcare professionals. Charlotte Perkins Gilman’s famous 1892 short story “The Yellow Wallpaper” offers a poignant example of this through its fictional narrator, a diarist many interpret to be suffering from postpartum depression. The fiction here does not stray far from reality: Gilman orchestrated her diarist’s experience to mirror her own, as both real author and fictional character suffocated from a melancholy only made worse by their physicians’ insistence on following the “Rest Cure.” While this instruction to cease all work and activity was a prevalent depression treatment at the time, Gilman, through “The Yellow Wallpaper,” reveals how the intervention ultimately harmed more than helped because it overlooked her—and, by extension, her fictional diarist’s— unique needs and identities. Today, while the ineffective Rest Cure no longer exists, applying observations from “The Yellow Wallpaper” to clinical research calls attention to underrepresentation in treatment development, a costly problem that could be mitigated by mindful incorporation of intersectionality theory into study designs.
Visualization of the existence of growth hormone secretagogue receptor in the rat nucleus accumbens
Authors: Lee Seohyeon , Cai Wen Ting , Yoon Hyung Shin , Kim Jeong-Hoon
Published: June 2024

The potential role of the ghrelin receptor, also known as the growth hormone secretagogue receptor (GHSR), within the nucleus accumbens (NAcc) in regulating drug addiction and feeding has been documented; however, the pattern of its expression in this site remains elusive. In this study, we characterized the expression patterns of GHSR1a and 1b, two subtypes of GHSRs, within the NAcc of the rat brain by immunohistochemistry. We visually detected GHSR signals, for the first time, at the protein level in the NAcc in which they were mostly expressed in neurons including both medium spiny neurons (MSNs) and non-MSNs. Furthermore, GHSR1a was found expressed as localized near the cellular membrane or some in the cytoplasm, whereas GHSR1b expressed solely throughout the large cytoplasmic area. The existence and subcellular expression pattern of GHSRs in the NAcc identified in this study will contribute to improving our understanding about the role of GHSR-mediated neurosignaling in feeding and drug addiction.
Leaf: an ultrafast filter for population-scale long-read SV detection
Authors: Pan Chenxu , Reinert Knut
Published: June 2024

Advances in sequencing technology have facilitated population-scale long-read structural variant (SV) detection. Arguably, one of the main challenges in population-scale analysis is developing effective computational pipelines. Here, we present a new filter-based pipeline for population-scale long-read SV detection. It better captures SV signals at an early stage than conventional assembly-based or alignment-based pipelines. Assessments in this work suggest that the filter-based pipeline helps better resolve intra-read rearrangements. Moreover, it is also more computationally efficient than conventional pipelines and thus may facilitate population-scale long-read applications.
Facilitators, barriers and support needs to GLA:D exercise adherence – a mixed method study
Authors: Matile Franziska , Nast Irina , Niedermann Karin
Published: June 2024

Background

Knee and hip osteoarthritis (OA) are among the most common musculoskeletal joint diseases worldwide. International guidelines recommend exercise and education as first-line interventions for their management. The Good Life with osteoArthritis Denmark (GLA:D) programme aims to achieve self-management using group exercise and education sessions. It also encourages participants to stay physically active and perform GLA:D exercises (GE) twice weekly after programme end. This study investigated the participants’ self-reported level of physical activity (PA) and self-reported adherence to the GE between five and 17 months after completion of the GLA:D programme and also explored the barriers, facilitators and support needs to achieve long-term adherence to GE.

Methods

A mixed method study using an exploratory sequential design was performed. A qualitative phase, involving semi-structured interviews and a focus group, led to the development of a questionnaire on participants’ level of PA, as well as ratings of the barriers, facilitators and support needs for the achievement of long-term adherence to GE. In a second quantitative phase, the survey was conducted online with former GLA:D participants from Switzerland. Descriptive statistical analysis and a group comparison between adherent and non-adherent participants to the GE were performed using Fisher’s exact test, odds ratio, and confidence interval.

Results

Eleven former GLA:D participants attended the interviews and focus group, and former GLA:D participants (30% response rate) participated in the survey. Of these, 84% (n = 285) reported to reach the recommended level of PA and 53% (n = 178) GE adherence. The top barrier to GE adherence was no/little self-discipline to perform GE (40%, n = 112) and the top facilitator was GE are easy to perform (93%, n = 300). The top 3 items regarding support needs to enhance GE adherence were a shortened version (max. 30 min) of the GE home programme (75%, n = 255), monthly continuation of small GE groups under GLA:D physiotherapists’ supervision (65%, n = 221), and monitoring with regular testing of individual progress (65%, n = 221).

Conclusions

The top barriers and facilitators should be considered by those responsible for the GLA:D programme and may need to be specifically addressed during and after the programme. The development of a shortened version of the GLA:D programme, a post-GLA:D group, and monitoring with regular testing seem crucial for enhancing GE adherence.

Clinical Trial Registration

not applicable.
A comprehensive analysis of m6A/m7G/m5C/m1A-related gene expression and immune infiltration in liver ischemia–reperfusion injury by integrating bioinformatics and machine learning algorithms
Authors: Meng Zhanzhi , Li Xinglong , Lu Shounan , Hua Yongliang , Yin Bing , Qian Baolin , Li Zhongyu , Zhou Yongzhi , Sergeeva Irina , Fu Yao , Ma Yong
Published: June 2024

Background

Liver ischemia–reperfusion injury (LIRI) is closely associated with immune infiltration, which commonly occurs after liver surgery, especially liver transplantation. Therefore, it is crucial to identify the genes responsible for LIRI and develop effective therapeutic strategies that target immune response. Methylation modifications in mRNA play various crucial roles in different diseases. This study aimed to identify potential methylation-related markers in patients with LIRI and evaluate the corresponding immune infiltration.

Methods

Two Gene Expression Omnibus datasets containing human liver transplantation data (GSE12720 and GSE151648) were downloaded for integrated analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted to investigate the functional enrichment of differentially expressed genes (DEGs). Differentially expressed methylation-related genes (DEMRGs) were identified by overlapping DEG sets and 65 genes related toN6-methyladenosine (m6A), 7-methylguanine (m7G), 5-methylcytosine (m5C), andN1-methyladenosine (m1A). To evaluate the relationship between DEMRGs, a protein–protein interaction (PPI) network was utilized. The core DEMRGs were screened using three machine learning algorithms: least absolute shrinkage and selection operator, random forest, and support vector machine-recursive feature elimination. After verifying the diagnostic efficacy using the receiver operating characteristic curve, we validated the expression of the core DEMRGs in clinical samples and performed relative cell biology experiments. Additionally, the immune status of LIRI was comprehensively assessed using the single sample gene set enrichment analysis algorithm. The upstream microRNA and transcription factors of the core DEMRGs were also predicted.

Results

In total, 2165 upregulated and 3191 downregulated DEGs were identified, mainly enriched in LIRI-related pathways. The intersection of DEGs and methylation-related genes yielded 28 DEMRGs, showing high interaction in the PPI network. Additionally, the core DEMRGsYTHDC1,METTL3,WTAP, andNUDT3demonstrated satisfactory diagnostic efficacy and significant differential expression and corresponding function based on cell biology experiments. Furthermore, immune infiltration analyses indicated that several immune cells correlated with all core DEMRGs in the LIRI process to varying extents.

Conclusions

We identified core DEMRGs (YTHDC1,METTL3,WTAP, andNUDT3) associated with immune infiltration in LIRI through bioinformatics and validated them experimentally. This study may provide potential methylation-related gene targets for LIRI immunotherapy.
Prebiotic galactooligosaccharide improves piglet growth performance and intestinal health associated with alterations of the hindgut microbiota during the peri-weaning period
Authors: Boston Timothy E. , Wang Feng , Lin Xi , Kim Sung Woo , Fellner Vivek , Scott Mark F. , Ziegler Amanda L. , Van Landeghem Laurianne , Blikslager Anthony T. , Odle Jack
Published: June 2024

Background

Weaning stress reduces growth performance and health of young pigs due in part to an abrupt change in diets from highly digestible milk to fibrous plant-based feedstuffs. This study investigated whether dietary galactooligosaccharide (GOS), supplemented both pre- and post-weaning, could improve growth performance and intestinal health via alterations in the hindgut microbial community.

Methods

Using a 3 × 2 factorial design, during farrowing 288 piglets from 24 litters received either no creep feed (FC), creep without GOS (FG–) or creep with 5% GOS (FG+) followed by a phase 1 nursery diet without (NG–) or with 3.8% GOS (NG+). Pigs were sampled pre- (D22) and post-weaning (D31) to assess intestinal measures.

Results

Creep fed pigs grew 19% faster than controls (P < 0.01) prior to weaning, and by the end of the nursery phase (D58), pigs fed GOS pre-farrowing (FG+) were 1.85 kg heavier than controls (P < 0.05). Furthermore, pigs fed GOS in phase 1 of the nursery grew 34% faster (P < 0.04), with greater feed intake and efficiency. Cecal microbial communities clustered distinctly in pre- vs. post-weaned pigs, based on principal coordinate analysis (P < 0.01). No effects of GOS were detected pre-weaning, but gruel creep feeding increased Chao1 α-diversity and altered several genera in the cecal microbiota (P < 0.05). Post-weaning, GOS supplementation increased some genera such asFusicatenibacterandCollinsella,whereas others decreased such asCampylobacterandFrisingicoccus(P < 0.05). Changes were accompanied by higher molar proportions of butyrate in the cecum of GOS-fed pigs (P < 0.05).

Conclusions

Gruel creep feeding effectively improves suckling pig growth regardless of GOS treatment. When supplemented post-weaning, prebiotic GOS improves piglet growth performance associated with changes in hindgut microbial composition.
Hematological profiles and mortality risk in critically ill and drug-resistant tuberculosis patients: insights from a longitudinal study
Authors: Ali Asmaa , Wu Liang , Moazen Eman M. , Elsawy Sawsan Bakr , Salama Khadiga S. M. , Ullah Kalim , Elfeky Seham Ezzat Fathy , Alharbi Sami H. , Saleh Mai M.
Published: June 2024

Background

While tuberculosis (TB) remains a significant global health threat, data on mortality in critically ill TB patients and those with drug-resistant TB (DR-TB) is limited. This study explores hematological profiles of critically ill TB patients and those with DR-TB, investigating associations with in-hospital and short-term mortality.

Methods

A longitudinal study of 269 patients with confirmed TB evaluated baseline blood cell counts and indices from medical records. We calculated in-hospital mortality and short-term prognosis, followed by analysis to identify predictors of mortality using hematological parameters.

Results

One-third of TB patients were critically ill (35.32%) and required intensive care unit (ICU) admission, while 14.5% had DR-TB, more common in females and smokers. Critically ill patients were older and tended to be non-smokers. DR-TB patients exhibited elevated lymphocyte and monocyte counts but lower neutrophil count and blood indices. Critically ill DS-TB patients had lower hemoglobin (Hb) and platelet (PLT) but higher total leucocytes count (TLC) and mean platelet volume (MPV). In-hospital mortality rate was 29.37%, significantly higher in critically ill DS-TB patients (74.74%). In-hospital mortality was 14-fold higher in critically ill DS-TB patients, 11-fold higher in stable DR-TB patients, and 6-fold higher in patients with comorbidities. Decreased Hb, monocyte level, and neutrophil to lymphocyte ratio (NLR) were significantly associated with in-hospital mortality. Predictors of short-term mortality included critical illness and comorbidities. However, the effect of DR-TB on short-term mortality disappeared. Decreasing Hb and TLC, especially neutrophils were significantly linked to short-term mortality. The utility of Hb in discriminating in-hospital and short-term mortality was very good, with AUC values of 78% and 79%, respectively. Cutoff values of less than 10 mg/dL and 9.75 mg/dL showed sensitivity ranging from 71 to 80% and specificity ranging from 75 to 80%, respectively.

Conclusion

This study provides valuable insights into patients with DR-TB and DS-TB with critically illness. We observed elevated lymphocyte and monocyte counts in DR-TB patients, as well as significant alterations in blood indices in critically ill patients. Importantly, the in-hospital mortality was notably higher in critically ill DS-TB patients, highlighting the importance of early recognition and aggressive management in this subgroup. Specifically, certain blood parameters such as hemoglobin, monocytes, neutrophils, and the NLR were associated with an increased risk of both in-hospital and short-term mortality. Furthermore, our findings underscore the prognostic significance of hematological parameters, particularly in resource-limited settings.
Associations Between Radiation Oncologist Demographic Factors and Segmentation Similarity Benchmarks: Insights From a Crowd-Sourced Challenge Using Bayesian Estimation
Authors: Wahid Kareem A. , Sahin Onur , Kundu Suprateek , Lin Diana , Alanis Anthony , Tehami Salik , Kamel Serageldin , Duke Simon , Sherer Michael V. , Rasmussen Mathis , Korreman Stine , Fuentes David , Cislo Michael , Nelms Benjamin E. , Christodouleas John P. , Murphy James D. , Mohamed Abdallah S.R. , He Renjie , Naser Mohammed A. , Gillespie Erin F. , Fuller Clifton D.
Published: June 2024

PURPOSE

The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors.

METHODS

Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference standard benchmark. The Dice similarity coefficient (DSC) was primarily used as a metric for the comparisons. DSC was stratified into binary groups on the basis of structure-specific expert-derived interobserver variability (IOV) cutoffs. Generalized linear mixed-effects models using Bayesian estimation were used to investigate the association between demographic variables and the binarized DSC for each disease site. Variables with a highest density interval excluding zero were considered to substantially affect the outcome measure.

RESULTS

Five hundred seventy-four, 110, 452, 112, and 48 segmentations were used for the breast, sarcoma, H&N, GYN, and GI cases, respectively. The median percentage of segmentations that crossed the expert DSC IOV cutoff when stratified by structure type was 55% and 31% for OARs and tumors, respectively. Regression analysis revealed that the structure being tumor-related had a substantial negative impact on binarized DSC for the breast, sarcoma, H&N, and GI cases. There were no recurring relationships between segmentation quality and demographic variables across the cases, with most variables demonstrating large standard deviations.

CONCLUSION

Our study highlights substantial uncertainty surrounding conventionally presumed factors influencing segmentation quality relative to benchmarks.
Sintilimab, doxorubicin and ifosfamide (AI) as first-line treatment in patients with advanced undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), myxoid liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS): A single-arm phase 2 trial.
Authors: Liu Xin , Guo Yanjing , Yan Wangjun , Chen Yong , Xu Yu , Wang Chun-Meng , Yao Weiqiang , Wang Jian , Yu Lin , Jiang Shiyu , Zhang Xiaowei , Luo Zhiguo
Published: June 2024

11505

Background: Anti-PD-1 antibody had showed encouraging activity as salvage treatment in patients with certain subtypes of advanced soft tissue sarcoma. However, its role in first-line setting is uncertain. We assessed the safety and activity of sintilimab, an anti-PD-1 antibody, combined with doxorubicin (ADM) and ifosfamide (IFO) in patients with advanced undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), myxoid liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS). Methods: This is a single-arm, phase 2 study. Systemic treatment naïve patients with metastatic or unresectable locally advanced UPS, SS, MLPS and DDLPS were treated with sintilimab (200mg, d1), ADM (60mg/m2, d1) and IFO (1.8 g/m2/d, d1-5) every 3 weeks for up to 6 cycles, followed by sintilimab maintenance until disease progression, unacceptable toxicities or up to 2 years. The primary endpoint was objective response rate (ORR, per RECIST 1.1), and secondary endpoints included progression free survival (PFS), overall survival (OS) and safety. Results: Between June 2020 and June 2023, 46 eligible patients were enrolled. 31 were male, and the median age was 47 years old. Of the 41 evaluable pts, ORR was 68.3% (28/41), including 7/8 (87.5%) UPS, 13/20 (65.0%) SS, 3/3 (100%) MLPS and 5/10 (50%) DDLPS patients. At a median follow-up time of 28.0 months (95% CI: 9.4-46.7 months), the median PFS and OS were 9.0 months (95% CI: 6.5-11.5 months) and 19.9 months (95% CI: 14.9-24.9 months), respectively. 1 DLT was observed in the first six patients during the DLT observation window. The most frequent ≥ grade 3 adverse events were leucopenia (50.0%), neutropenia (45.7%), thrombocytopenia (21.7%), anemia (21.7%), and febrile neutropenia (21.7%). Conclusions: The primary endpoint of ORR was met. This study indicated promising efficacy and safety of sintilimab combined with AI in the first-line treatment of UPS, SS, MLPS and DDLPS. Clinical trial information: NCT04356872 .
Extracorporeal irradiation and reimplantation for bone sarcomas: Medium- and long-term oncologic and functional outcomes.
Authors: Mishra Biplab , Shah Mandip C , Jani Kinjal
Published: June 2024

11524

Background: Extracorporeal irradiation is an effective and established method for limb salvage in the management of malignant bone tumours.We analyzed the oncological and functional outcomes of extracorporeal radiotherapy (ECRT) and reimplantation done for bone sarcomas. Methods: 67 patients (29 osteosarcoma, 27 Ewing’s sarcoma, 11 others; mean age 16 years) were treated with ECRT between 2010 and 2022. Femur was commonest bone (33) followed by tibia (11) and humerus (11). 48 had a metadiaphyseal while 19 had osteoarticular resections. A single dose of 50 Gy was delivered to the resected bone segments. The irradiated bones were reimplanted immediately as a biological graft. Construct was stabilized with long locking plates. Osteoarticular ECRT was coupled with joint replacement. Patients were treated with chemotherapy as per standard protocol. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. Results: The mean resected length of bone was 17 cm (9 to 26). All 67 patients were available at a mean follow-up of 66 months (22 to 166). The mean time to union for all osteotomy sites was 6 months (2 to 17): metaphyseal osteotomy sites united quicker than diaphyseal osteotomy sites (3.8 months (3 to 6) versus 9.5 months (4 to 17)). 2 deep infections necessitated removal of the ECRT segment. There were 2 local recurrences in soft-tissue needing amputation. 6 of the remaining 113 (5.3%) junctions remained ununited which needed additional bone grafting. 5/6 junctions united after bone grafting. 1 remained ununited needing cementation across the segment. At the time of final follow-up, 47 patients were free of disease, one was alive with disease and 19 had died of disease. The mean Musculoskeletal Tumor Society Score at the last follow-up was 26 (18 to 30). Conclusions: The radiated bone acts as a size-matched allograft and has very good union rates. The complication rates are very low. Extracorporeal irradiation is an oncologically safe and biological reconstruction technique for limb salvage in sarcomas and has good functional results. It should be recommended to all suitable patients.
Apatinib combined with ifosfamide and etoposide versus ifosfamide and etoposide in relapsed or refractory osteosarcoma (OAIE/PKUPH-sarcoma 11): A multicenter, randomized controlled trial.
Authors: Xie Lu , Xu Jie , Sun Xin , Liang Xin , Liu Kuisheng , Sun Kunkun , Li Yuan , Liu Rong , Wang Du , Shao Shurong , Li Peiyu , Pang Zheng , Zhou Guangxin , Wu Sujia , Hua Yingqi , Hu Haiyan , Yang Yi , Ji Tao , Guo Wei , Tang Xiaodong
Published: June 2024

11527

Background: Retrospective studies have suggested the potential of apatinib, an anti-angiogenesis tyrosine kinase inhibitor, plus ifosfamide and etoposide (IE) over IE in advanced osteosarcoma. This trial aimed to further compared apatinib plus IE versus IE alone in patients with advanced osteosarcomas post first-line chemotherapy failure. Methods: In this multicenter, randomized controlled trial, patients with histologically confirmed osteosarcoma, progressing after at least one prior line of chemotherapy, were randomized (2:1) to either apatinib plus IE or IE alone. The apatinib plus IE group received oral apatinib 500mg daily plus ifosfamide (1.8 g/m2/d) and etoposide (100 mg/m2/d) on days 1-3, every 3 weeks. The IE group received IE on days 1-5, every 3 weeks. Apatinib was continued until disease progression or for a maximum of one year, and IE was administered for up to 10 cycles. The primary endpoint was progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1. Results: A total of 81 patients were enrolled, with 53 receiving apatinib and IE, while 28 using IE alone. The median follow-up period was 9.5 (interquartile range, 7.1 to 13.0) months. The apatinib plus IE group showed a median PFS of 5.5 months (95% confidence interval [CI], 3.9 to 6.7), compared to 3.4 months (95% CI, 1.4 to 4.6) in the IE group, yielding a hazard ratio of 0.41 (95% CI, 0.24 to 0.71), P=0.0010. Objective response rates were 32.1% (95% CI, 19.9 to 46.3) for the apatinib plus IE group and 25.0% (95% CI, 10.7 to 44.9) for the IE group. Disease control rates were numerically higher in the apatinib plus IE group at 90.6% (95% CI, 79.3 to 96.9), compared to 60.7% (95% CI, 40.6 to 78.5) in the IE group. The median time to response was 1.4 months (95% CI, 1.2 to 2.6) for the apatinib plus IE group and 1.5 months (95% CI, 1.3 to 2.0) for the IE group. Duration of response also favored the apatinib plus IE group, with a median of 6.1 months (95% CI, 1.9 to 8.0) compared to 4.1 months (95% CI, 1.7 to not estimated [NE]) in the IE group. The median overall survival has not yet been reached in either group. Grade 3-4 treatment-related adverse events occurred in 69.8% of patients in the apatinib plus IE group and 64.3% in the IE group, with the most common events being white blood cell count decreased and neutrophil count decreased. Conclusions: Apatinib plus IE demonstrated a significant improvement in PFS in patients with advanced osteosarcomas, with an acceptable safety. Clinical trial information: NCT05277480 . [Table: see text]