bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effect of an evolving amyloid and tau pathology on brain phospholipids and bioactive lipid mediators in rat models of Alzheimer-like pathology
Authors: Do Carmo Sonia , Kautzmann Marie-Audrey I. , Bhattacharjee Surjyadipta , Jun Bokkyoo , Steinberg Carolyn , Emmerson Joshua T. , Malcolm Janice C. , Bonomo Quentin , Bazan Nicolas G. , Cuello A. Claudio 
Published: July 2024

Abstract
Background
Brain inflammation contributes significantly to the pathophysiology of Alzheimer’s disease, and it is manifested by glial cell activation, increased production of cytokines/chemokines, and a shift in lipid mediators from a pro-homeostatic to a pro-inflammatory profile. However, whether the production of bioactive lipid mediators is affected at earlier stages, prior to the deposition of Aβ plaques and tau hyperphosphorylation, is unknown. The differential contribution of an evolving amyloid and tau pathology on the composition and abundance of membrane phospholipids and bioactive lipid mediators also remains unresolved.

Methods
In this study, we examined the cortical levels of DHA- and AA-derived bioactive lipid mediators and of membrane phospholipids by liquid chromatography with tandem mass spectrometry in transgenic rat models of the Alzheimer’s-like amyloid and tau pathologies at early and advanced pathological stages.

Results
Our findings revealed a complex balance between pro-inflammatory and pro-resolving processes in which tau pathology has a more pronounced effect compared to amyloid pathology. At stages preceding tau misfolding and aggregation, there was an increase in pro-resolving lipid mediators (RVD6 and NPD1), DHA-containing phospholipids and IFN-γ levels. However, in advanced tau pathology displaying NFT-like inclusions, neuronal death, glial activation and cognitive deficits, there was an increase in cytokine and PGD2, PGE2, and PGF2α generation accompanied by a drop in IFN-γ levels. This pathology also resulted in a marked increase in AA-containing phospholipids. In comparison, pre-plaque amyloid pathology already presented high levels of cytokines and AA-containing phospholipids together with elevated RVD6 and NPD1 levels. Finally, Aβ plaque deposition was accompanied by a modest increase in prostaglandins, increased AA-containing phospholipids and reduced DHA-containing phospholipids.

Conclusions
Our findings suggest a dynamic trajectory of inflammatory and lipid mediators in the evolving amyloid and tau pathologies and support their differing roles on membrane properties and, consequentially, on signal transduction.
Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling
Authors: Gerelkhuu Zayakhuu , Park Sehee , Lee Kyoung Hwa , Kim Yong Chan , Kwon Sook Jin , Song Kyoung-Ho , Kim Eu Suk , Song Young Goo , Park Yoon Soo , Ahn Jin Young , Choi Jun Yong , Choi Won Suk , Bae Seongman , Kim Sung-Han , Kim Shin-Woo , Kwon Ki Tae , Jeong Hye Won , Peck Kyong Ran , Kang Eun-Suk , Koh June-Young , Ko Jae-Hoon , Yoon Tae Hyun 
Published: July 2024

Abstract
Background
Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear.

Methods
This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points.

Results
We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21–63). There was a significant inverse correlation between age and Sab levels after the second dose (slope − 14.96, P = 0.032), and this was more pronounced after the third dose (slope − 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age.

Conclusions
Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.
Safety & efficacy of a robotic hip exoskeleton on outpatient stroke rehabilitation
Authors: Macaluso Rebecca , Giffhorn Matt , Prokup Sara , Cleland Brice , Lee Jusuk , Lim Bokman , Lee Minhyung , Lee Hwang-Jae , Madhavan Sangeetha , Jayaraman Arun 
Published: July 2024

Abstract
Objective
The objective of this study was to analyze the safety and efficacy of using a robotic hip exoskeleton designed by Samsung Electronics Co., Ltd., Korea, called the Gait Enhancing and Motivating System-Hip (GEMS-H), in assistance mode only with the poststroke population in an outpatient-rehabilitation setting.

Methods
Forty-one participants with an average age of 60 and average stroke latency of 6.5 years completed this prospective, single arm, interventional, longitudinal study during the COVID-19 pandemic. Significant modifications to the traditional outpatient clinical environment were made to adhere to organizational physical distancing policies as well as guidelines from the Centers for Disease Control. All participants received gait training with the GEMS-H in assistance mode for 18 training sessions over the course of 6–8 weeks. Performance-based and self-reported clinical outcomes were assessed at four time points: baseline, midpoint (after 9 training sessions), post (after 18 training sessions), and 1-month follow up. Daily step count was also collected throughout the duration of the study using an ankle-worn actigraphy device. Additionally, corticomotor excitability was measured at baseline and post for 4 bilateral lower limb muscles using transcranial magnetic stimulation.

Results
By the end of the training program, the primary outcome, walking speed, improved by 0.13 m/s (p < 0.001). Secondary outcomes of walking endurance, balance, and functional gait also improved as measured by the 6-Minute Walk Test (47 m, p < 0.001), Berg Balance Scale (2.93 points, p < 0.001), and Functional Gait Assessment (1.80 points, p < 0.001). Daily step count significantly improved with and average increase of 1,750 steps per day (p < 0.001). There was a 35% increase in detectable lower limb motor evoked potentials and a significant decrease in the active motor threshold in the medial gastrocnemius (-5.7, p < 0.05) after training with the device.

Conclusions
Gait training with the GEMS-H exoskeleton showed significant improvements in walking speed, walking endurance, and balance in persons with chronic stroke. Day-to-day activity also improved as evidenced by increased daily step count. Additionally, corticomotor excitability changes suggest that training with this device may help correct interhemispheric imbalance typically seen after stroke.

Trial Registration
This study is registered with ClinicalTrials.gov (NCT04285060).
Adverse cardiac events of hypercholesterolemia are enhanced by sitagliptin in sprague dawley rats
Authors: Palfrey Henry A. , Kumar Avinash , Pathak Rashmi , Stone Kirsten P. , Gettys Thomas W. , Murthy Subramanyam N. 
Published: July 2024

Abstract
Background
Cardiovascular disease (CVD) affects millions worldwide and is the leading cause of death among non-communicable diseases. Western diets typically comprise of meat and dairy products, both of which are rich in cholesterol (Cho) and methionine (Met), two well-known compounds with atherogenic capabilities. Despite their individual effects, literature on a dietary combination of the two in the context of CVD are limited. Therefore, studies on the combined effects of Cho and Met were carried out using male Sprague Dawley rats. An additional interest was to investigate the cardioprotective potential of sitagliptin, an anti-type 2 diabetic drug. We hypothesized that feeding a dietary combination of Cho and Met would result in adverse cardiac effects and would be attenuated upon administration of sitagliptin.

Methods
Adult male Sprague-Dawley rats were fed either a control (Con), high Met (1.5%), high Cho (2.0%), or high Met (1.5%) + high Cho (2.0%) diet for 35 days. They were orally gavaged with an aqueous preparation of sitagliptin (100 mg/kg/d) or vehicle (water) from day 10 through 35. On day 36, rats were euthanized, and tissues were collected for analysis.

Results
Histopathological evaluation revealed a reduction in myocardial striations and increased collagen deposition in hypercholesterolemia (HChol), responses that became exacerbated upon sitagliptin administration. Cardiac pro-inflammatory and pro-fibrotic responses were adversely impacted in similar fashion. The addition of Met to Cho (MC) attenuated all adverse structural and biochemical responses, with or without sitagliptin.

Conclusions
Adverse cardiac outcomes in HChol were enhanced by the administration of sitagliptin, and such effects were alleviated by Met. Our findings could be significant for understanding or revisiting the risk-benefit evaluation of sitagliptin in type 2 diabetics, and especially those who are known to consume atherogenic diets.
Quantitative PSMA-PET parameters in localized prostate cancer: prognostic and potential predictive value
Authors: Bela Andela Stephanie , Amthauer Holger , Furth Christian , Rogasch Julian M. , Beck Marcus , Mehrhof Felix , Ghadjar Pirus , van den Hoff Jörg , Klatte Tobias , Tahbaz Rana , Zips Daniel , Hofheinz Frank , Zschaeck Sebastian 
Published: July 2024

Abstract
Background
PSMA-PET is increasingly used for staging prostate cancer (PCA) patients. However, it is not clear if quantitative imaging parameters of positron emission tomography (PET) have an impact on disease progression and are thus important for the prognosis of localized PCA.

Methods
This is a monocenter retrospective analysis of 86 consecutive patients with localized intermediate or high-risk PCA and PSMA-PET before treatment The quantitative PET parameters maximum standardized uptake value (SUVmax), tumor asphericity (ASP), PSMA tumor volume (PSMA-TV), and PSMA total lesion uptake (PSMA-TLU = PSMA-TV × SUVmean) were assessed for their prognostic significance in patients with radiotherapy or surgery. Cox regression analyses were performed for biochemical recurrence-free survival, overall survival (OS), local control, and loco-regional control (LRC).

Results
67% of patients had high-risk disease, 51 patients were treated with radiotherapy, and 35 with surgery. Analysis of metric PET parameters in the whole cohort revealed a significant association of PSMA-TV (p = 0.003), PSMA-TLU (p = 0.004), and ASP (p < 0.001) with OS. Upon binarization of PET parameters, several other parameters showed a significant association with clinical outcome. When analyzing high-risk patients according to the primary treatment approach, a previously published cut-off for SUVmax (8.6) showed a significant association with LRC in surgically treated (p = 0.048), but not in primary irradiated (p = 0.34) patients. In addition, PSMA-TLU (p = 0.016) seemed to be a very promising biomarker to stratify surgical patients.

Conclusion
Our data confirm one previous publication on the prognostic impact of SUVmax in surgically treated patients with high-risk PCA. Our exploratory analysis indicates that PSMA-TLU might be even better suited. The missing association with primary irradiated patients needs prospective validation with a larger sample size to conclude a predictive potential.
Trial registration Due to the retrospective nature of this research, no registration was carried out.
Identification of truncated variants in GLI family zinc finger 3 (GLI3) associated with polydactyly
Authors: Wang Run-Yan , Xiong Qin , Chang Si-Hua , Jin Jie-Yuan , Xiang Rong , Zeng Lei , Yu Fang 
Published: July 2024

Abstract
Background
Polydactyly is a prevalent congenital anomaly with an incidence of 2.14 per 1000 live births in China. GLI family zinc finger 3 (GLI3) is a classical causative gene of polydactyly, and serves as a pivotal transcription factor in the hedgehog signaling pathway, regulating the development of the anterior-posterior axis in limbs.

Methods
Three pedigrees of polydactyly patients were enrolled from Hunan Province, China. Pathogenic variants were identified by whole-exome sequencing (WES) and Sanger sequencing.

Results
Three variants in GLI3 were identified in three unrelated families, including a novel deletion variant (c.1372del, p.Thr458GlnfsTer44), a novel insertion-deletion (indel) variant (c.1967_1968delinsAA, p.Ser656Ter), and a nonsense variant (c.2374 C > T, p.Arg792Ter). These variants were present exclusively in patients but not in healthy individuals.

Conclusions
We identified three pathogenic GLI3 variants in polydactyly patients, broadening the genetic spectrum of GLI3 and contributing significantly to genetic counseling and diagnosis for polydactyly.
SMARCA4 controls state plasticity in small cell lung cancer through regulation of neuroendocrine transcription factors and REST splicing
Authors: Redin Esther , Sridhar Harsha , Zhan Yingqian A. , Pereira Mello Barbara , Zhong Hong , Durani Vidushi , Sabet Amin , Manoj Parvathy , Linkov Irina , Qiu Juan , Koche Richard P. , de Stanchina Elisa , Astorkia Maider , Betel Doron , Quintanal-Villalonga Álvaro , Rudin Charles M. 
Published: July 2024

Abstract
Introduction
Small Cell Lung Cancer (SCLC) can be classified into transcriptional subtypes with distinct degrees of neuroendocrine (NE) differentiation. Recent evidence supports plasticity among subtypes with a bias toward adoption of low-NE states during disease progression or upon acquired chemotherapy resistance. Here, we identify a role for SMARCA4, the catalytic subunit of the SWI/SNF complex, as a regulator of subtype shift in SCLC.

Methods
ATACseq and RNAseq experiments were performed in SCLC cells after pharmacological inhibition of SMARCA4. DNA binding of SMARCA4 was characterized by ChIPseq in high-NE SCLC patient derived xenografts (PDXs). Enrichment analyses were applied to transcriptomic data. Combination of FHD-286 and afatinib was tested in vitro and in a set of chemo-resistant SCLC PDXs in vivo.

Results
SMARCA4 expression positively correlates with that of NE genes in both SCLC cell lines and patient tumors. Pharmacological inhibition of SMARCA4 with FHD-286 induces the loss of NE features and downregulates neuroendocrine and neuronal signaling pathways while activating non-NE factors. SMARCA4 binds to gene loci encoding NE-lineage transcription factors ASCL1 and NEUROD1 and alters chromatin accessibility, enhancing NE programs. Enrichment analysis applied to high-confidence SMARCA4 targets confirmed neuron related pathways as the top GO Biological processes regulated by SMARCA4 in SCLC. In parallel, SMARCA4 also controls REST, a known suppressor of the NE phenotype, by regulating SRRM4-dependent REST transcript splicing. Furthermore, SMARCA4 inhibition drives ERBB pathway activation in SCLC, rendering SCLC tumors sensitive to afatinib.

Conclusions
This study nominates SMARCA4 as a key regulator of the NE state plasticity and defines a novel therapeutic strategy for SCLC.
Parapneumonic empyema in children: a scoping review of the literature
Authors: Buonsenso Danilo , Cusenza Francesca , Passadore Lucrezia , Bonanno Francesca , Calanca Carolina , Mariani Francesco , Di Martino Carlotta , Rasmi Sonia , Esposito Susanna 
Published: July 2024

AbstractCommunity-acquired pneumonia can lead to a serious complication called empyema, which refers to pus within the pleural space. While it poses a significant threat to morbidity, particularly in children, it is fortunately not associated with high mortality rates. However, determining the best course of management for children, including decisions regarding antibiotic selection, administration methods, and treatment duration, remains a topic of ongoing debate. This scoping review aims to map the existing literature on empyema in children, including types of studies, microbiology, therapies (both antimicrobial and surgical) and patient outcomes. We systematically searched PubMed and SCOPUS using the terms “pediatric” (encompassing children aged 0 to 18 years) and “pleural empyema” to identify all relevant studies published since 2000. This search adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA ScR) checklist.A total of 127 studies was included. Overall, 15 attempted to compare medical treatments (alone or in combination with pleural drainage or fibrinolysis) with more invasive surgical approaches, and six studies compared diverse surgical interventions. However, the diversity of study designs makes it difficult to derive firm conclusions on the optimal approach to pediatric empyema. The heterogeneity in inclusion criteria, pharmacological/surgical approaches and settings limit the ability to draw definitive conclusions. Overall, 78 out of 10,896 children (0.7%) included in the review died, with mortality being higher in Asia and Africa. Our scoping review highlights important gaps regarding several aspects of empyema in children, including specific serotypes of the most common bacteria involved in the etiology, the optimal pharmacological and surgical approach, and the potential benefits of newer antibiotics with optimal lung penetration. New trials, designed on a multi-country level a higher number of patients and more rigorous inclusion criteria and designs, should be urgently funded.
Modelling the demographic history of human North African genomes points to a recent soft split divergence between populations
Authors: Serradell Jose M. , Lorenzo-Salazar Jose M. , Flores Carlos , Lao Oscar , Comas David 
Published: July 2024

AbstractBackgroundNorth African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa.ResultsWe conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa.ConclusionsWe have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.
Epigenomic identification of vernalization cis-regulatory elements in winter wheat
Authors: Liu Yanhong , Liu Pan , Gao Lifeng , Li Yushan , Ren Xueni , Jia Jizeng , Wang Lei , Zheng Xu , Tong Yiping , Pei Hongcui , Lu Zefu 
Published: July 2024

AbstractBackgroundWinter wheat undergoes vernalization, a process activated by prolonged exposure to low temperatures. During this phase, flowering signals are generated and transported to the apical meristems, stimulating the transition to the inflorescence meristem while inhibiting tiller bud elongation. Although some vernalization genes have been identified, the keycis-regulatory elements and precise mechanisms governing this process in wheat remain largely unknown.ResultsIn this study, we construct extensive epigenomic and transcriptomic profiling across multiple tissues—leaf, axillary bud, and shoot apex—during the vernalization of winter wheat. Epigenetic modifications play a crucial role in eliciting tissue-specific responses and sub-genome-divergent expressions during vernalization. Notably, we observe that H3K27me3 primarily regulates vernalization-induced genes and has limited influence on vernalization-repressed genes. The integration of these datasets enables the identification of 10,600 putative vernalization-related regulatory elements including distal accessible chromatin regions (ACRs) situated 30Kb upstream ofVRN3, contributing to the construction of a comprehensive regulatory network. Furthermore, we discover that TaSPL7/15, integral components of the aging-related flowering pathway, interact with theVRN1promoter andVRN3distal regulatory elements. These interactions finely regulate their expressions, consequently impacting the vernalization process and flowering.ConclusionsOur study offers critical insights into wheat vernalization’s epigenomic dynamics and identifies the putative regulatory elements crucial for developing wheat germplasm with varied vernalization characteristics. It also establishes a vernalization-related transcriptional network, and uncovers that TaSPL7/15 from the aging pathway participates in vernalization by directly binding to theVRN1promoter andVRN3distal regulatory elements.