bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breaking barriers: exploring mechanisms behind opening the blood–brain barrier
Authors: Stamp Melanie E. M. , Halwes Michael , Nisbet David , Collins David J. 
Published: November 2023

AbstractThe blood–brain barrier (BBB) is a selectively permeable membrane that separates the bloodstream from the brain. While useful for protecting neural tissue from harmful substances, brain-related diseases are difficult to treat due to this barrier, as it also limits the efficacy of drug delivery. To address this, promising new approaches for enhancing drug delivery are based on disrupting the BBB using physical means, including optical/photothermal therapy, electrical stimulation, and acoustic/mechanical stimulation. These physical mechanisms can temporarily and locally open the BBB, allowing drugs and other substances to enter. Focused ultrasound is particularly promising, with the ability to focus energies to targeted, deep-brain regions. In this review, we examine recent advances in physical approaches for temporary BBB disruption, describing their underlying mechanisms as well as evaluating the utility of these physical approaches with regard to their potential risks and limitations. While these methods have demonstrated efficacy in disrupting the BBB, their safety, comparative efficacy, and practicality for clinical use remain an ongoing topic of research.
Much room for change: access to surgical care for stateless individuals in Pakistan
Authors: Thobani Humza , Shah Mashal Murad , Ehsan Anam N , Khan Sadaf 
Published: November 2023

Abstract
Background
As developing countries take steps towards providing universal essential surgery, ensuring the equitable distribution of such care for underrepresented populations is a vital function of the global surgery community. Unfortunately, in the context of the global “stateless”, there remains much room for improvement.

Key issues
Inherent structural deficiencies, such as lack of adequate population data on stateless communities, absent health coverage policies for stateless individuals, and minimal patient-reported qualitative data on barriers to surgical service delivery prevent stateless individuals from receiving the care they require – even when healthcare infrastructure to provide such care exists. The authors therefore propose more research and targeted interventions to address the systemic issues that prevent stateless individuals from accessing surgical care.

Conclusion
It is essential to address the aforementioned barriers in order to improve stateless populations’ access to surgical care. Rigorous empirical and qualitative research provides an important avenue through which these structural issues may be addressed.
Findings from a Malaysian multicentre study on oropharyngeal squamous cell carcinoma
Authors: Sathasivam Hans Prakash , Davan Sangeetha Passu , Chua Szu May , Rohaizat Rahmuna Fazlina , Japar Rohaizam , Zakaria Zahirrudin , Ahmad Abd Razak , Hashim Hasmah , Marimuthu Shashi Gopalan , Liew Yew Toong , Yong Doh Jeing , Vairavan Pappathy , Mohan Singh Avatar Singh , Goh Benjamin Hong Beng , Yusof Zulkifli , Abu Dahari Khairul Azlan Shahril , Haron Ali , Mansor Masaany , Ibrahim Mohd Zambri , Muhammad Abdul Kadar Shiraz Qamil , Hamal Mohamad Hazri , Wan Mohamad Wan Emelda ,   Malaysian Head & Neck Cancer Research Group
Published: November 2023

Abstract
Background
In addition to the conventional aetiologic agents of oropharyngeal squamous cell carcinoma (OPSCC) such as tobacco usage, alcohol consumption and betel quid usage, it has been established that a proportion of OPSCC are driven by persistent oncogenic human papillomavirus (HPV) infections. Currently, there is a lack of data on the burden of HPV- associated OPSCC in Asian countries including Malaysia.

Methods
A cross-sectional multicentre study with tissue analysis of Malaysian patients diagnosed with primary OPSCC within a five-year period, from 2015 to 2019 between 01/01/2015 to 31/12/2019 was undertaken. Determination of HPV status was carried out using p16INK4a immunohistochemistry on tissue microarrays constructed from archived formalin-fixed paraffin-embedded tissue.

Results
From the cases identified, 184 cases had sufficient tissue material for analysis. Overall, median age at diagnosis was 63.0 years (IQR = 15) and 76.1% of patients were males. In our cohort, 35.3% of patients were Indian, 34.2% were Chinese, 21.2% were Malay and 9.2% were from other ethnicities. The estimated prevalence of HPV-associated OPSCC in our cohort was 31.0% (CI 24.4–38.2%). The median age for the HPV-associated OPSCC sub-group of patients was not significantly lower than the median age of patients with HPV-independent OPSCC. More than half of HPV-associated OPSCC was seen in patients of Chinese ethnicity (54.4%). Patients with HPV-associated OPSCC had a much better overall survival than patients with HPV-independent OPSCC (Log rank test; p < 0.001). Patients with HPV-associated OPSCC with no habit-related risk factors such as smoking, were found to have much better overall survival when compared to all other sub-groups.

Conclusions
The findings from our study suggests that prevalence of HPV-associated OPSCC in Malaysia, though not as high as some developed countries, is however on an upward trend. HPV-associated OPSCC appears to be more frequently encountered in patients of Chinese ethnicity. Conventional risk-factors associated with OPSCC such as smoking, alcohol consumption and betel quid chewing should still be considered when estimating prognosis of patients with HPV-associated OPSCC.
External validation of the modified sepsis renal angina index for prediction of severe acute kidney injury in children with septic shock
Authors: Stanski Natalja L. , Basu Rajit K. , Cvijanovich Natalie Z. , Fitzgerald Julie C. , Bigham Michael T. , Jain Parag N. , Schwarz Adam J. , Lutfi Riad , Thomas Neal J. , Baines Torrey , Haileselassie Bereketeab , Weiss Scott L. , Atreya Mihir R. , Lautz Andrew J. , Zingarelli Basilia , Standage Stephen W. , Kaplan Jennifer , Chawla Lakhmir S. , Goldstein Stuart L. 
Published: November 2023

Abstract
Background
Acute kidney injury (AKI) occurs commonly in pediatric septic shock and increases morbidity and mortality. Early identification of high-risk patients can facilitate targeted intervention to improve outcomes. We previously modified the renal angina index (RAI), a validated AKI prediction tool, to improve specificity in this population (sRAI). Here, we prospectively assess sRAI performance in a separate cohort.

Methods
A secondary analysis of a prospective, multicenter, observational study of children with septic shock admitted to the pediatric intensive care unit from 1/2019 to 12/2022. The primary outcome was severe AKI (≥ KDIGO Stage 2) on Day 3 (D3 severe AKI), and we compared predictive performance of the sRAI (calculated on Day 1) to the original RAI and serum creatinine elevation above baseline (D1 SCr > Baseline +). Original renal angina fulfillment (RAI +) was defined as RAI ≥ 8; sepsis renal angina fulfillment (sRAI +) was defined as RAI ≥ 20 or RAI 8 to < 20 with platelets < 150 × 103/µL.

Results
Among 363 patients, 79 (22%) developed D3 severe AKI. One hundred forty (39%) were sRAI + , 195 (54%) RAI + , and 253 (70%) D1 SCr > Baseline + . Compared to sRAI-, sRAI + had higher risk of D3 severe AKI (RR 8.9, 95%CI 5–16, p < 0.001), kidney replacement therapy (KRT) (RR 18, 95%CI 6.6–49, p < 0.001), and mortality (RR 2.5, 95%CI 1.2–5.5, p = 0.013). sRAI predicted D3 severe AKI with an AUROC of 0.86 (95%CI 0.82–0.90), with greater specificity (74%) than D1 SCr > Baseline (36%) and RAI + (58%). On multivariable regression, sRAI + retained associations with D3 severe AKI (aOR 4.5, 95%CI 2.0–10.2, p < 0.001) and need for KRT (aOR 5.6, 95%CI 1.5–21.5, p = 0.01).

Conclusions
Prediction of severe AKI in pediatric septic shock is important to improve outcomes, allocate resources, and inform enrollment in clinical trials examining potential disease-modifying therapies. The sRAI affords more accurate and specific prediction than context-free SCr elevation or the original RAI in this population.
Methylation-directed regulatory networks determine enhancing and silencing of mutation disease driver genes and explain inter-patient expression variation
Authors: Edrei Yifat , Levy Revital , Kaye Daniel , Marom Anat , Radlwimmer Bernhard , Hellman Asaf 
Published: November 2023

Abstract
Background
Common diseases manifest differentially between patients, but the genetic origin of this variation remains unclear. To explore possible involvement of gene transcriptional-variation, we produce a DNA methylation-oriented, driver-gene-wide dataset of regulatory elements in human glioblastomas and study their effect on inter-patient gene expression variation.

Results
In 175 of 177 analyzed gene regulatory domains, transcriptional enhancers and silencers are intermixed. Under experimental conditions, DNA methylation induces enhancers to alter their enhancing effects or convert into silencers, while silencers are affected inversely. High-resolution mapping of the association between DNA methylation and gene expression in intact genomes reveals methylation-related regulatory units (average size = 915.1 base-pairs). Upon increased methylation of these units, their target-genes either increased or decreased in expression. Gene-enhancing and silencing units constitute cis-regulatory networks of genes. Mathematical modeling of the networks highlights indicative methylation sites, which signified the effect of key regulatory units, and add up to make the overall transcriptional effect of the network. Methylation variation in these sites effectively describe inter-patient expression variation and, compared with DNA sequence-alterations, appears as a major contributor of gene-expression variation among glioblastoma patients.

Conclusions
We describe complex cis-regulatory networks, which determine gene expression by summing the effects of positive and negative transcriptional inputs. In these networks, DNA methylation induces both enhancing and silencing effects, depending on the context. The revealed mechanism sheds light on the regulatory role of DNA methylation, explains inter-individual gene-expression variation, and opens the way for monitoring the driving forces behind deferential courses of cancer and other diseases.
Supporting physical activity for mobility in older adults with mobility limitations (SuPA Mobility): study protocol for a randomized controlled trial
Authors: Rice Jordyn , Li Linda C. , Davis Jennifer C. , Pahor Marco , Madden Kenneth , Wei Nathan , Wong Hubert , Skelton Dawn A. , McCormick Sioban , Falck Ryan S. , Barha Cindy K. , Rhodes Ryan E. , Loomba Sohail , Sadatsafavi Mohsen , Liu-Ambrose Teresa 
Published: November 2023

Abstract
Background
Limited mobility in older adults consistently predicts both morbidity and mortality. As individuals age, the rates of mobility disability increase from 1.0% in people aged 15–24 to 20.6% in adults over 65 years of age. Physical activity can effectively improve mobility in older adults, yet many older adults do not engage in sufficient physical activity. Evidence shows that increasing physical activity by 50 min of moderate intensity physical activity in sedentary older adults with mobility limitations can improve mobility and reduce the incidence of mobility disability. To maximize the healthy life span of older adults, it is necessary to find effective and efficient interventions that can be delivered widely to prevent mobility limitations, increase physical activity participation, and improve quality of life in older adults. We propose a randomized controlled trial to assess the effect of a physical activity health coaching intervention on mobility in older adults with mobility limitations.

Methods
This randomized controlled trial among 290 (145 per group) community-dwelling older adults with mobility limitations, aged 70–89 years old, will compare the effect of a physical activity health coaching intervention versus a general healthy aging education program on mobility, as assessed with the Short Physical Performance Battery. The physical activity health coaching intervention will be delivered by exercise individuals who are trained in Brief Action Planning. The coaches will use evidence-based behavior change techniques including goal-setting, action planning, self-monitoring, and feedback to improve participation in physical activity by a known dose of 50 min per week. There will be a total of 9 health coaching or education sessions delivered over 26 weeks with a subsequent 26-week follow-up period, wherein both groups will receive the same duration and frequency of study visits and activities.

Discussion
The consequences of limited mobility pose a significant burden on the quality of life of older adults. Our trial is novel in that it investigates implementing a dose of physical activity that is known to improve mobility in older adults utilizing a health coaching intervention.

Trial registration
ClinicalTrials.gov Protocol Registration System: NCT05978336; registered on 28 July 2023.
Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis
Authors: Sakhawat Azra , Khan Muhammad Umer , Rehman Raima , Khan Samiullah , Shan Muhammad Adnan , Batool Alia , Javed Muhammad Arshad , Ali Qurban 
Published: November 2023

AbstractBrain-Derived Neurotrophic Factor (BDNF) is a neurotrophin gene family gene that encodes proteins vital for the growth, maintenance, and survival of neurons in the nervous system. The study aimed to screen natural compounds against BDNF variant (V66M), which affects memory, cognition, and mood regulation. BDNF variant (V66M) as a target structure was selected, and Vitamin D, Curcumin, Vitamin C, and Quercetin as ligands structures were taken from PubChem database. Multiple tools like AUTODOCK VINA, BIOVIA discovery studio, PyMOL, CB-dock, IMOD server, Swiss ADEMT, and Swiss predict ligands target were used to analyze binding energy, interaction, stability, toxicity, and visualize BDNF-ligand complexes. Compounds Vitamin D3, Curcumin, Vitamin C, and Quercetin with binding energies values of − 5.5, − 6.1, − 4.5, and − 6.7 kj/mol, respectively, were selected. The ligands bind to the active sites of the BDNF variant (V66M) via hydrophobic bonds, hydrogen bonds, and electrostatic interactions. Furthermore, ADMET analysis of the ligands revealed they exhibited sound pharmacokinetic and toxicity profiles. In addition, an MD simulation study showed that the most active ligand bound favorably and dynamically to the target protein, and protein–ligand complex stability was determined. The finding of this research could provide an excellent platform for discovering and rationalizing novel drugs against stress related to BDNF (V66M). Docking, preclinical drug testing and MD simulation results suggest Quercetin as a more potent BDNF variant (V66M) inhibitor and forming a more structurally stable complex.
Intelligent deep reinforcement learning-based scheduling in relay-based HetNets
Authors: Chen Chao , Wu Zhengyang , Yu Xiaohan , Ma Bo , Li Chuanhuang 
Published: November 2023

AbstractWe consider a fundamental file dissemination problem in a two-hop relay-based heterogeneous network consisting of a macro base station, a half-duplex relay station, and multiple users. To minimize the dissemination delay, rateless code is employed at the base station. Our goal is to find an efficient channel-aware scheduling policy at the half-duplex relay station, i.e., either fetch a packet from the base station or broadcast a packet to the users at each time slot, such that the file dissemination delay is minimized. We formulate the scheduling problem as a Markov decision process and propose an intelligent deep reinforcement learning-based scheduling algorithm. We also extend the proposed algorithm to adapt to dynamic network conditions. Simulation results demonstrate that the proposed algorithm performs very close to a lower bound on the dissemination delay and significantly outperforms baseline schemes.
Physiological responses and algae inhibition of Pontederia cordata to simulated eutrophication and acid rain co-pollution
Authors: Li Yan , Qi Xi , Xin Jianpan , Zhao Chu , Tian Runan 
Published: November 2023

Abstract
Background
Eutrophication and acid rain are two threats that many water bodies must contend with. Eutrophication and climate change have accelerated widespread outbreaks of cyanobacterial blooms as both have become more severe. Pontederiacordata, a garden ornamental plant, can inhibit some algae growth and remove total nitrogen (TN) and total phosphorus (TP) from the water. In this study, we investigated how simulated acid rain and eutrophication co-pollution affected P.cordata's growth physiology and ability to inhibit algae growth.

Results
Under mild eutrophication (2 mg·L−1 TN, 0.4 mg·L−1 TP, and 15 mg·L−1 CODMn) or weak acid rain (pH = 5.0), P.cordata alleviated the degree of cell membrane lipid peroxidation by stabilizing superoxide dismutase (SOD) and catalase (CAT) activities in the leaves, allowing for normal plant growth. Under mild eutrophication and acid rain conditions, cultured P.cordata water samples maintained strong algae inhibition by reducing the Chl a content and SOD activity of Microcystisaeruginosa cells. Compound stress where acid rain was the primary inhibitory factor along with moderate or severe eutrophication inhibited P.cordata growth, which probably reduced the input of algae-inhibiting allelochemicals, thus reducing its ability to inhibit algae.

Conclusions
In summary, P. cordata has application potential in mild eutrophic water and acid rain (pH ≥ 4). These findings provide guidance for further research on phytoremediation and algae control in scenarios of compound pollution.
Predicting the prognosis, immune response, and immunotherapy in head and neck squamous cell carcinoma using a novel risk model based on anoikis-related lncRNAs
Authors: Deng Hongxia , Wei Zhengyu , Du Juan , Shen Zhisen , Zhou Chongchang 
Published: November 2023

Abstract
Background
Head and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous and metastatic disease. Anoikis, which is a specific type of programmed apoptosis, is involved in tumor metastasis, tissue homeostasis, and development. Herein, we constructed an anoikis-related long non-coding RNA (lncRNA) signature to predict the prognosis, immune responses, and therapeutic effects in HNSCC patients.

Methods
A total of 501 HNSCC samples were acquired from the TCGA database and randomly classified into the training and validation groups (1:1 ratio). Thereafter, the results derived from the training set were analyzed with the LASSO regression analysis, and a novel anoikis-related lncRNA risk model was constructed. Time-dependent ROC curves and Kaplan–Meier analysis were carried out to assess the diagnostic value and survival outcomes. A nomogram was utilized to predict the prognostic accuracy. Furthermore, we studied the tumor microenvironment, tumor mutation burden, enrichment pathways, and the response to chemotherapy and immunotherapy.

Results
Seven anoikis-related lncRNAs (AC015878.1, CYTOR, EMSLR, LINC01503, LINC02084, RAB11B-AS1, Z97200.1) were screened to design a novel risk model, which was recognized as the independent prognostic factor for HNSCC patients. The findings implied that low-risk patients showed significantly longer OS, PFS, and DSS compared to those high-risk patients. The two groups that were classified using the risk model showed significant differences in their immune landscape. The risk model also predicted that low-risk HNSCC patients could attain a better response to immunotherapy, while high-risk patients would be more sensitive to gemcitabine, docetaxel, and cisplatin.

Conclusions
We constructed a novel risk model that could be employed for effectively predicting patient prognosis with a good independent prognostic value for HNSCC patients. Furthermore, this model could be used for designing new immunotherapeutic and chemotherapeutic strategies, and it helps clinicians establish personalized and detailed strategies for HNSCC patients.
A novel tumor purity and immune infiltration-related model for predicting distant metastasis-free survival in prostate cancer
Authors: Su Qiang , Zhu Yongbei , He Bingxi , Dai Bin , Mu Wei , Tian Jie 
Published: November 2023

Abstract
Background
umor cells, immune cells and stromal cells jointly modify tumor development and progression. We aim to explore the potential effects of tumor purity on the immune microenvironment, genetic landscape and prognosis in prostate cancer (PCa).

Methods
Tumor purity of prostate cancer patients was extracted from The cancer genome atlas (TCGA). Immune cellular proportions were calculated by the CIBERSORT. To identify critical modules related to tumor purity, we used weighted gene co-expression network analysis (WGCNA). Using STRING and Cytoscape, protein–protein interaction (PPI) networks were constructed and analyzed. A Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Disease Ontology (DO), and Gene Set Enrichment Analysis (GSEA) enrichment analysis of identified modules was conducted. To identify the expression of key genes at protein levels, we used the Human Protein Atlas (HPA) platform.

Results
A model of tumor purity score (TPS) was constructed in the gene expression omnibus series (GSE) 116,918 cohort. TCGA cohort served as a validation set and was employed to validate the TPS. TPS model, as an independent prognostic factor of distant metastasis‐free survival (DMFS) in PCa. Patients had higher tumor purity and better prognosis in the low-TPS group. Tumor purity was related to the infiltration of mast cells and macrophage cells positively, whereas related to the infiltration of dendritic cells, T cells and B cells negatively in PCa. The nomogram based on TPS, Age, Gleason score and T stage had a good predictive value and could evaluate the prognosis of PCa metastasis. GO and KEGG enrichment analyses showed that hub genes mainly participate in T cell activation and T-helper lymphocytes (TH) differentiation. Hub genes were mainly enriched in primary immunodeficiency disease, according to DO analysis. SLAMF8 was identified as the most critical gene by Cytoscape and HPA analysis.

Conclusions
Dynamic changes in the immune microenvironment associated with tumor purity could correlate with a poor DMFS of low-purity PCa. The TPS can predict the DMFS of PCa. In addition, prostate cancer metastases may be related to immunosuppression caused by a disorder of the immune microenvironment.
An analysis of economic growth using input–output tables
Authors: Mendoza Marco Antonio Marquez 
Published: November 2023

AbstractTwo perspectives on the analysis of economic growth have developed within the input–output framework. On the one hand, Leontief proposed a dynamic model, where investment supplies the necessary capital stock needed to produce future output. On the other hand, Structural Decomposition Analysis assumes that changes in the output level are dependent on the behaviour of the technological and final demand components. This paper examines the differences between input–output tables of different periods to explain growth, as well as the contribution of the final demand components in the phenomenon. Further, the article provides examples based on the coefficient tables of five OECD economies, between 1995 and 2011, to illustrate the relevance of the method proposed here.