bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of ferroptosis-associated molecular subtypes and immunological characteristics in lupus nephritis based on artificial neural network learning
Authors: Zhang Li , Yan Qing , Lin Miao , He Juanjuan , Tian Jie , Chen Zhihan , Hong Fuyuan 
Published: July 2024

AbstractBackgroundLupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) with poor treatment outcomes. The role and underlying mechanisms of ferroptosis in LN remain largely unknown. We aimed to explore ferroptosis-related molecular subtypes and assess their prognostic value in LN patients.MethodsMolecular subtypes were classified on the basis of differentially expressed ferroptosis-related genes (FRGs) via the Consensus ClusterPlus package. The enriched functions and pathways, immune infiltrating levels, immune scores, and immune checkpoints were compared between the subgroups. A scoring algorithm based on the subtype-specific feature genes identified by artificial neural network machine learning, referred to as the NeuraLN, was established, and its immunological features, clinical value, and predictive value were evaluated in patients with LN. Finally, immunohistochemical analysis was performed to validate the expression and role of feature genes in glomerular tissues from LN patients and controls.ResultsA total of 10 differentially expressed FRGs were identified, most of which showed significant correlation. Based on the 10 FRGs, LN patients were classified into two ferroptosis subtypes, which exhibited significant differences in immune cell abundances, immune scores, and immune checkpoint expression. A NeuraLN-related protective model was established based on nine subtype-specific genes, and it exhibited a robustly predictive value in LN. The nomogram and calibration curves demonstrated the clinical benefits of the protective model. The high-NeuraLN group was closely associated with immune activation. Clinical specimens demonstrated the alterations of ALB, BHMT, GAMT, GSTA1, and HAO2 were in accordance with bioinformatics analysis results, GSTA1 and BHMT were negatively correlated with the severity of LN.ConclusionThe classification of ferroptosis subtypes and the establishment of a protective model may form a foundation for the personalized treatment of LN patients.
Significance of physical factors on activities of daily living in patients with tetraplegia after spinal cord injury: a retrospective study
Authors: Yun Kimin , Lim Jin-cheol , Kim Onyoo 
Published: July 2024

Abstract
Background
Tetraplegia is a debilitating sequela of spinal cord injury (SCI). However, comprehensive approaches for determining the influence of various factors on activities of daily living (ADL) in patients with tetraplegia are limited. Therefore, this study aimed to determine the influence of physical factors on ADL in patients with tetraplegia after adjusting for demographic, SCI-related, and cognitive factors.

Methods
This retrospective cross-sectional study enrolled 201 patients with tetraplegia who underwent inpatient rehabilitation at the National Rehabilitation Center in South Korea between 2019 and 2021. Patients’ mean age was 50.5 years (standard deviation, 16.3), and 170 (84.6%) were men. The Korean Spinal Cord Independence Measure III (K-SCIM III) was used as the main outcome measure to assess patients’ ADL ability. Hierarchical multiple regression modeling was conducted with K-SCIM as the dependent variable to examine the level of functioning and relative influencing factors.

Results
Upper-extremity motor score (UEMS), upper-extremity spasticity and sitting balance scores were significant predictors of self-care; lower-extremity motor score (LEMS), musculoskeletal pain of shoulder, and sitting balance were significant predictors of respiratory and sphincter management; UEMS, LEMS, and sitting balance score were significant predictors of mobility; and UEMS, LEMS, musculoskeletal pain of shoulder, and sitting balance scores were significant predictors of the K-SCIM III total score after adjustment for demographic, SCI-related, and cognitive factors.

Conclusions
Physical factors had the greatest impact on all subscores and the K-SCIM III total score. Upper- and lower-extremity muscle strength and sitting balance significantly affected functional ability across all subscores.
Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways
Authors: Martino David , Schultz Nikki , Kaur Ravinder , van Haren Simon D. , Kresoje Nina , Hoch Annmarie , Diray-Arce Joann , Su Jessica Lasky , Levy Ofer , Pichichero Michael ,   in association with the IDEAL Consortium
Published: July 2024

Abstract
Background
Infants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripheral blood mononuclear cells from respiratory infection allergy/asthma-prone (IAP) infants and non-infection allergy/asthma prone (NIAP) were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fisher's exact p-value = 0.02).

Results
An endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPL), a TLR agonist, partially reversed this signature at a subset of CpGs, suggesting the potential for epigenetic remodeling.

Conclusions
This proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for future investigation.
Heat-related illness and dementia: a study integrating epidemiological and experimental evidence
Authors: Kuo Wan-Yin , Huang Chien-Cheng , Chen Chi-An , Ho Chung-Han , Tang Ling‑Yu , Lin Hung-Jung , Su Shih-Bin , Wang Jhi-Joung , Hsu Chien-Chin , Chang Ching-Ping , Guo How-Ran 
Published: July 2024

Abstract
Background
Heat-related illness (HRI) is commonly considered an acute condition, and its potential long-term consequences are not well understood. We conducted a population-based cohort study and an animal experiment to evaluate whether HRI is associated with dementia later in life.

Methods
The Taiwan National Health Insurance Research Database was used in the epidemiological study. We identified newly diagnosed HRI patients between 2001 and 2015, but excluded those with any pre-existing dementia, as the study cohort. Through matching by age, sex, and the index date with the study cohort, we selected individuals without HRI and without any pre-existing dementia as a comparison cohort at a 1:4 ratio. We followed each cohort member until the end of 2018 and compared the risk between the two cohorts using Cox proportional hazards regression models. In the animal experiment, we used a rat model to assess cognitive functions and the histopathological changes in the hippocampus after a heat stroke event.

Results
In the epidemiological study, the study cohort consisted of 70,721 HRI patients and the comparison cohort consisted of 282,884 individuals without HRI. After adjusting for potential confounders, the HRI patients had a higher risk of dementia (adjusted hazard ratio [AHR] = 1.24; 95% confidence interval [CI]: 1.19–1.29). Patients with heat stroke had a higher risk of dementia compared with individuals without HRI (AHR = 1.26; 95% CI: 1.18–1.34). In the animal experiment, we found cognitive dysfunction evidenced by animal behavioral tests and observed remarkable neuronal damage, degeneration, apoptosis, and amyloid plaque deposition in the hippocampus after a heat stroke event.

Conclusions
Our epidemiological study indicated that HRI elevated the risk of dementia. This finding was substantiated by the histopathological features observed in the hippocampus, along with the cognitive impairments detected, in the experimental heat stroke rat model.
Prevalence, trends, and specialized palliative care utilization in Taiwanese children and young adults with life-limiting conditions between 2008 and 2017: a nationwide population-based study
Authors: Lin Shih-Chun , Huang Mei-Chih 
Published: July 2024

Abstract
Background
Previous studies have shown a growing need for pediatric palliative care, but there is a lack of knowledge in many countries concerning prevalence of service use among children and young adults with life-limiting conditions. This study aimed to estimate (1) the annual prevalence of children and young adults with a life-limiting condition, and (2) their specialized palliative care and other healthcare utilization.

Methods
Data from the Health and Welfare Data Science Center in Taiwan were used. All children and young adults aged 0–25 years recorded in inpatient or outpatient data, and infants aged < 1 year in death data with a life-limiting condition diagnostic code from 2008 to 2017 were recruited. Poisson regression was used to estimate the crude and adjusted relative risk of prevalence of life-limiting conditions with 95% confidence intervals, adjusted for age and sex, and to evaluate the trend in prevalence of each life-limiting diagnostic groups, in specialized palliative care and other service use.

Results
Data contained 236,250 individuals with a life-limiting condition, of which oncological and congenital abnormalities were the most common. There was an annualized increase over 10 years in the prevalence of life-limiting conditions of 36.4%, from 45,311 cases (59.4 per 10,000 population) to 52,226 cases (81.0 per 10,000 population), with the highest prevalence in individuals aged 21–25 years. All diagnostic groups showed significant increases in prevalence (p < .001) with the exception of oncology, circulatory, and “other” group. Specialized palliative care services, including family consultation, shared care, home visits have increased in use over time (p < .001), while inpatient hospice has slightly decreased. The highest prevalence of healthcare use was for traditional Chinese medicine (237.1 per 1,000 population in 2017), but this decreased over time (p < .001).

Conclusions
Due to a growing trend towards multidisciplinary care, healthcare professionals and policymakers must engage and take action to expand specialized palliative care and integrate delivery of other healthcare services. Traditional Chinese medicine having a decreasing slope, yet still the highest prevalence of use, needs further attention.
Validation of the Charlson Comorbidity Index for the prediction of 30-day and 1-year mortality among patients who underwent hip fracture surgery
Authors: de Haan Eveline , van Oosten Benthe , van Rijckevorsel Veronique. A. J. I. M. , Kuijper T. Martijn , de Jong Louis , Roukema Gert R. 
Published: July 2024

Abstract
Introduction
The aim of our study was to validate the original Charlson Comorbidity Index (1987) (CCI) and adjusted CCI (2011) as a prediction model for 30-day and 1-year mortality after hip fracture surgery. The secondary aim of this study was to verify each variable of the CCI as a factor associated with 30-day and 1-year mortality.

Methods
A prospective database of two-level II trauma teaching hospitals in the Netherlands was used. The original CCI from 1987 and the adjusted CCI were calculated based on medical history. To validate the original CCI and the adjusted CCI, the CCI was plotted against the observed 30-day and 1-year mortality, and the area under the curve (AUC) was calculated.

Results
A total of 3523 patients were included in this cohort study. The mean of the original CCI in this cohort was 5.1 (SD ± 2.0) and 4.6 (SD ± 1.9) for the adjusted CCI. The AUCs of the prediction models were 0.674 and 0.696 for 30-day mortality for the original and adjusted CCIs, respectively. The AUCs for 1-year mortality were 0.705 and 0.717 for the original and adjusted CCIs, respectively.

Conclusions
A higher original and adjusted CCI is associated with a higher mortality rate. The AUC was relatively low for 30-day and 1-year mortality for both the original and adjusted CCIs compared to other prediction models for hip fracture patients in our cohort. The CCI is not recommended for the prediction of 30-day and 1-year mortality in hip fracture patients.
Exergetic performance evaluation of louvered finned solar air heater: an experimental investigation
Authors: Chand Subhash , Ghritlahre Harish Kumar , Singh Ajay Partap 
Published: July 2024

AbstractSolar energy is a promising source of renewable energy, and solar air heaters are an important application for utilizing this energy source. This study investigates the exergetic performance of a louvered fin solar air heater (LFSAH) through experimental analysis conducted during day time from 9 am to 3 pm under identical operating and metrological parameters. Exergy analysis based on the 2nd law of thermodynamics is used to assess the quality of exergy losses and useful energy output and is deemed suitable for LFSAH design. The study experimentally examines the exergetic performance of LFSAH with various fin spacings and compares the results with those of a plane solar air heater (PSAH). The exergy efficiency is optimized by considering the fin spacing (ranging from 2 to 5 cm) and mass flow rate (MFR) (ranging from 0.007 to 0.0158 kg/s) through an exergy analysis of internal and exterior exergy losses. Based on the result analysis, the LFSAH’s maximum exergy efficiency was achieved at 3.31% for a fin spacing of 2 cm and a MFR of 0.007 kg/s. The study found that incorporating louvered fins into the SAH substantially improves its exergetic performance compared to the PSAH.
BY101921: Restoring interferon signaling and anti-tumor immunity through PARP7 inhibition.
Authors: Yu Jinming , Sun Yuping , Wei Yonggang , Ye Fei , Zhu Yuqin , Chen Yang , Liu Rui 
Published: July 2024

3123 Background: PARP7( TIPARP), a member of monoPARP family, catalyzes ADP-ribose transfer to specific amino acids within itself and other substrate proteins, utilizing nicotinamide adenine dinucleotide (NAD+) as substrate. It plays a vital role in various biological processes such as gene expression, protein degradation, and cellular stress response. PARP7 amplification has been observed in various cancers, including squamous cell carcinoma, ovarian cancer, breast cancer, and pancreatic ductal adenocarcinoma. Over expression of PARP7 correlates with reduced survival in squamous cell carcinoma. PARP7's MARylation of α-tubulin induces microtubule instability, promoting proliferation and migration of ovarian cancer cells. As a negative regulator of tumor cell nucleic acid sensing, PARP7 inhibits TBK1 through. This, in turn, hampers the cGAS-STING signal pathway and downregulates the type Ⅰ interferon expression. BY101921, developed by Chengdu Baiyu Pharmaceutical, is a highly selective PARP7 inhibitor demonstrating significant anti-tumor effect in vitro and in vivo, both alone and in combination with anti-PD-1. Methods: Enzymatic evaluation was conducted on BY101921 to assess its selectivity among major PARP family members. PK studies were investigated in both mouse and dog species. The anti-tumor activity of BY101921, both as a monotherapy and in combo with anti-PD-1, was investigated in NCI-H1373 and CT26 tumor-bearing mice, respectively. In terms of anti-tumor mechanism, pSTAT1, IFN-β and CXCL10 levels were analyzed in RAW264.7 cells and CT26 tumor-bearing tissues. In addition, the effect of BY101921 on the type Ⅰ interferon signaling pathway was systematically evaluated. Results: BY101921 demonstrated outstanding selectivity as a PARP7 inhibitor, displaying limited off-target effects on PARP1/2, reducing the risk of systemic toxicity, especially hematologic effects. In mice and dogs, BY101921 revealed favorable PK characteristics following oral administration. In vivo, BY101921 exhibited potent inhibition of tumor growth as a monotherapy, and its combination with anti-PD-1 further enhanced its anti-tumor efficacy, with excellent tolerability in animals. Mechanism of action studies showed that BY101921 generated an anti-tumor immune response by upregulating pSTAT1 levels and promoting the secretion of IFN-β and CXCL10, thereby restoring the type Ⅰ interferon signaling pathway. Conclusions: BY101921, a potent and selective PARP7 inhibitor, demonstrates significant anti-tumor efficacy both as a monotherapy and in combo with anti-PD-1, while maintaining excellent tolerability in animal models. With favorable drug-like properties and a promising safety profile, BY101921 holds potential as an enhanced therapeutic option for cancer patients. At present, clinical studies investigating BY101921 as a single agent and in combo with anti-PD-1 are in the recruitment phase.
Avelumab first-line maintenance (1LM) for advanced urothelial carcinoma (aUC): Long-term outcomes from JAVELIN Bladder 100 in patients (pts) with low tumor burden.
Authors: Bellmunt Joaquim , Powles Thomas , Park Se Hoon , Voog Eric , Valderrama Begoña Pérez , Gurney Howard , Ullén Anders , Loriot Yohann , Sridhar Srikala S. , Tsuchiya Norihiko , Sternberg Cora N. , Aragon-Ching Jeanny B. , Petrylak Daniel P. , Climent Duran Miguel A. , Tyroller Karin , Hoffman Jason , Jacob Natalia , Grivas Petros , Gupta Shilpa 
Published: July 2024

4566 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab 1LM + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in pts with aUC that had not progressed with 1L platinum-based chemotherapy (PBC). Results led to the incorporation of avelumab 1LM into international guidelines. Prior analyses have shown that low tumor burden (eg, nonvisceral metastases or lymph node [LN]-only disease) is associated with better outcomes in pts with aUC receiving immune checkpoint inhibitors. We report post hoc analyses of efficacy and safety in subsets of pts with low tumor burden from JAVELIN Bladder 100. Methods: Eligible pts with unresectable locally advanced (LA) or metastatic UC without progression after 1L PBC were randomized 1:1 to receive avelumab + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS measured from randomization; secondary endpoints included PFS and safety. In this post hoc analysis, pts with nonvisceral metastases included those with LA disease or only nonvisceral disease, including bone metastasis, at randomization. Results: In the avelumab + BSC and BSC alone arms, 159 and 159 pts had nonvisceral metastases and 51 and 51 pts had LN-only disease, of whom 42 and 35 pts had LN-only disease in the pelvic/retroperitoneal area. At the efficacy data cutoff (June 4, 2021), median follow-up was ≥38 mo in both arms (≥2 y in all pts). In all subgroups, OS and PFS were prolonged with avelumab + BSC vs BSC alone (Table). Incidence of treatment-related adverse events (TRAEs) with avelumab were similar across subgroups. In the avelumab + BSC and BSC alone arms, subsequent anticancer drug treatment was received by 90 (56.6%) vs 119 pts (74.8%) with nonvisceral metastases, 27 (52.9%) vs 39 pts (76.5%) with LN-only disease, and 22 (52.4%) vs 27 pts (77.1%) with pelvic/retroperitoneal LN-only disease. Conclusions: Exploratory analyses suggest that avelumab 1LM has pronounced efficacy and manageable toxicity in pts with aUC who have low tumor burden, supporting its use as a standard of care in this setting. Clinical trial information: NCT02603432 . [Table: see text]
A randomised, controlled, multicentre trial of imiquimod versus radiotherapy for lentigo maligna.
Authors: Hong Angela M , Lo Serigne N , Fogarty Gerald B , Stretch Jonathan , Wang Wei , Penas Pablo Fernandez , Martin Richard CW , Foote Matthew C , Soyer Hans Peter , Ruben Jeremy , Mar Victoria , Rocha Lilian , Wratten Christopher , Collgros Helena , Pereira Amanda Regio , Melhoranse Gouveia Bruna , Scolyer Richard A , King Madeleine T , Guitera Pascale 
Published: July 2024

9502 Background: Lentigo maligna (LM) is a form of melanoma in situ that occurs mainly on sun exposed skin. For patients with LM who are not suitable for surgery due to location, size, patient preference or co-morbidities, topical imiquimod or radiotherapy are alternative non-surgical treatments. There are no prospective randomized controlled trial data to form the basis of any recommendations for the management of LM. This multi-institutional, international randomized phase 3 trial evaluated the efficacy and safety of imiquimod verus radiotherapy for patients with LM. The primary hypothesis was that treatment of LM with topical imiquimod would result in fewer treatment failures than radiotherapy. Methods: Patients aged > 18 years old with LM not suitable for surgery were randomly assigned (1:1) to imiquimod or radiotherapy. The primary endpoint was treatment failure within 24 months. Secondary endpoints included development of invasive disease within the area, side effects and patient-reported quality of life (QOL) assessed with validated questionnaires (skin-specific Skindex-16 and generic EQ-5D-5L). Results: Between August 2015 and November 2021, 126 patients were randomised from 8 centres (imiquimod 60, radiotherapy 58 in final analysis). The median age was 72 years and 94.9% of lesions were on the head and neck area. Median follow-up was 27 months (range 3-62 months). Six (10.5%) patients in the imiquimod group and 12 (24.0%) patients in the radiotherapy group developed recurrence within 24 months (OR 2.68, 95% CI, 0·92-7.8, p = 0.063). Median time to recurrence was not reached in either group. Treatment failure was significantly different within the subgroup of patients who had reflectance confocal microscopy (RCM) follow up of the LM (imiquimod 4/46, 8.7% radiotherapy 13/52 25.0%; OR 3.50 95% CI 1.05-11.65, p = 0.033). Only one RCM feature was associated with failure at 24 months and significantly different between treatment groups : the presence of atypical round cells at the dermal-epidermal junction (6.9 % of imiquimod failure and 27% of radiotherapy failure: p = 0.035). There were no differences between trial groups in patient-reported skin symptoms (itching, burning/stinging, pain, irritation), skin-specific emotional and functional QOL impacts, or generic QOL at any time points. Conclusions: Both imiquimod and radiotherapy are valid, well-tolerated and efficient non-surgical options for LM. There is no significant difference in the acute or long term QoL for the two treatments. Clinical trial information: NCT02394132 .