bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers and facilitators to health care access for people experiencing homelessness in four European countries: an exploratory qualitative study
Authors: Carmichael Christina , Schiffler Tobias , Smith Lee , Moudatsou Maria , Tabaki Ioanna , Doñate-Martínez Ascensión , Alhambra-Borrás Tamara , Kouvari Matina , Karnaki Pania , Gil-Salmeron Alejandro , Grabovac Igor 
Published: October 2023

Abstract
Background
People experiencing homelessness (PEH) are known to be at higher risk of adverse health outcomes and premature mortality when compared to the housed population and often face significant barriers when attempting to access health services. This study aimed to better understand the specific health care needs of PEH and the barriers and facilitators associated with their timely and equitable access to health services in the European context.

Methods
We conducted an exploratory cross-national qualitative study involving people with lived experience of homelessness and health and social care professionals in Austria, Greece, Spain, and the UK. A total of 69 semi-structured interviews comprising 15 social care professionals, 19 health care professionals, and 35 PEH were completed, transcribed, and analysed thematically.

Results
Findings were organised into three overarching themes relating to the research question: (a) Health care needs of PEH, (b) Barriers to health care access, and (c) Facilitators to health care access. Overall, the general health of PEH was depicted as extremely poor, and mainstream health services were portrayed as ill-equipped to respond to the needs of this population. Adopting tailored approaches to care, especially involving trusted professionals in the delivery of care, was identified as a key strategy for overcoming existing barriers.

Conclusions
The results of this study indicate there to be a high degree of consistency in the health care needs of PEH and the barriers and facilitators associated with their access to health care across the various European settings. Homelessness in itself is recognized to represent an essential social determinant of health, with PEH at risk of unequal access to health services. Changes are thus required to facilitate PEH’s access to mainstream primary care. This can also be further complemented by investment in ‘in-reach’ services and other tailored and person-centred forms of health care.

Trial registration
This study was registered retrospectively on June 6, 2022, in the registry of ClinicalTrials.gov under the number NCT05406687.
Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches
Authors: Hasan Nazeer , Nadaf Arif , Imran Mohammad , Jiba Umme , Sheikh Afsana , Almalki Waleed H. , Almujri Salem Salman , Mohammed Yousuf Hussain , Kesharwani Prashant , Ahmad Farhan Jalees 
Published: October 2023

AbstractSkin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.
Graphical Abstract
Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation
Authors: Wang Kangchun , Wang Xin , Pan Qi , Zhao Bei 
Published: October 2023

AbstractPancreatic cancer (PC) is one of the most common malignancies. Surgical resection is a potential curative approach for PC, but most patients are unsuitable for operations when at the time of diagnosis. Even with surgery, some patients may still experience tumour metastasis during the operation or shortly after surgery, as precise prognosis evaluation is not always possible. If patients miss the opportunity for surgery and resort to chemotherapy, they may face the challenging issue of chemotherapy resistance. In recent years, liquid biopsy has shown promising prospects in disease diagnosis, treatment monitoring, and prognosis assessment. As a noninvasive detection method, liquid biopsy offers advantages over traditional diagnostic procedures, such as tissue biopsy, in terms of both cost-effectiveness and convenience. The information provided by liquid biopsy helps clinical practitioners understand the molecular mechanisms underlying tumour occurrence and development, enabling the formulation of more precise and personalized treatment decisions for each patient. This review introduces molecular biomarkers and detection methods in liquid biopsy for PC, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), noncoding RNAs (ncRNAs), and extracellular vesicles (EVs) or exosomes. Additionally, we summarize the applications of liquid biopsy in the early diagnosis, treatment response, resistance assessment, and prognostic evaluation of PC.
Periodontitis is associated with stroke
Authors: Zheng Xiaodan , Li Xin , Zhen Juanying , Xue Dai , Hu Jun , Cao Qing , Xu Aimin , Cheung Bernard Man Yung , Wu Jun , Li Chao 
Published: October 2023

Abstract
Background
Periodontitis is considered as a risk factor for cardiovascular diseases and atherosclerosis. However, the relationship between periodontitis and stroke is rarely studied. Therefore, we aimed to explore the relationship between periodontitis and stroke.

Methods
Statistical analysis was performed using the complex sampling design. We analyzed data on 6,460 participants, representing 92,856,028 American citizens aged 30 years or older, who had valid data on periodontitis and stroke from the National Health and Nutrition Examination Survey 2009–2014. We used clinical attachment level and probing pocket depth precisely to determine periodontitis and it is the first time to use such a precise method for exploring the relationship between periodontitis and stroke.

Results
39.9% of participants had periodontitis and 2.1% of participants had a record of stroke diagnosis. Stroke was associated with severity levels of periodontitis (p for trend = 0.018). The odds ratio for stroke was significantly elevated in the severe periodontitis and moderate periodontitis participants compared to participants without periodontitis (OR for severe periodontitis: 2.55, 95% CI 1.25–5.21; OR for moderate periodontitis: 1.71, 95% CI 1.17–2.50). After adjusting for race/ethnicity and sex, the association remained significant (p for trend = 0.009). After further adjusting for BMI, hypercholesterolemia, diabetes, alcohol consumption and physical activity, the association still existed (p for trend = 0.027). The association was significant consistently after further adjusting for age (p for trend = 0.033).

Conclusions
In this nationally representative study, we found an association between periodontitis and stroke. The risk of stroke in participants with severe periodontitis and moderate periodontitis was 2.55 times and 1.71times as high as those without periodontitis. Dental health management may be of benefit to stroke prevention.
Proteasome inhibition protects blood–brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer’s disease model
Authors: Vulin Milica , Zhong Yu , Maloney Bryan J. , Bauer Björn , Hartz Anika M. S. 
Published: October 2023

Abstract
Background
Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods
We treated hAPP mice with the proteasome inhibitor BTZ or a combination of BTZ with the P-gp inhibitor cyclosporin A (CSA) for 2 weeks. Vehicle-treated wild-type (WT) mice were used as a reference for normal P-gp protein expression and transport activity. In addition, we used the opioid receptor agonist loperamide as a P-gp substrate in tail flick assays to indirectly assess P-gp transport activity at the blood–brain barrier in vivo. We also determined P-gp protein expression by Western blotting, measured P-gp transport activity levels in isolated brain capillaries with live cell confocal imaging and assessed Aβ plasma and brain levels with ELISA.

Results
We found that 2-week BTZ treatment of hAPP mice restored P-gp protein expression and transport activity in brain capillaries to levels found in WT mice. We also observed that hAPP mice displayed significant loperamide-induced central antinociception compared to WT mice indicating impaired P-gp transport activity at the blood–brain barrier of hAPP mice in vivo. Furthermore, BTZ treatment prevented loperamide-induced antinociception suggesting BTZ protected P-gp loss in hAPP mice. Further, BTZ-treated hAPP mice had lower Aβ40 and Aβ42 brain levels compared to vehicle-treated hAPP mice.

Conclusions
Our data indicate that BTZ protects P-gp from proteasomal degradation in hAPP mice, which helps to reduce Aβ brain levels. Our data suggest that the proteasome system could be exploited for a novel therapeutic strategy in AD, particularly since increasing Aβ transport across the blood–brain barrier may prove an effective treatment for patients.
Advancements of radiotherapy for recurrent head and neck cancer in modern era
Authors: Zhang Shu , Zeng Ni , Yang Jiangping , He Jinlan , Zhu Fubin , Liao Wenjun , Xiong Maoqi , Li Yan 
Published: October 2023

AbstractHead and neck cancer is a kind of cancer which can be eradicated from radical radiation therapy. However, with best efforts, nearly 40% patients will experience locoregional recurrence. Locoregional recurrence is the main cause of cancer-related death in head and neck cancers, so local treatments play a key role in improving progression free survival. In the last decades, radiation techniques have been tremendously developed, highly conformal radiation techniques such as intensity-modulated radiotherapy, stereotactic body radiation therapy, brachytherapy and proton or heavy ion radiation therapy have their unique radiobiological advances. Although reirradiation is widely used in clinical practice, but little is known when comparing the different techniques. In this review, we will provide a comprehensive overview of the role of reirradiation in recurrent head and neck cancers including radiation techniques, patient selection, overall clinical benefits, and toxicities.
Towards deep-learning (DL) based fully automated target delineation for rectal cancer neoadjuvant radiotherapy using a divide-and-conquer strategy: a study with multicenter blind and randomized validation
Authors: Geng Jianhao , Zhu Xianggao , Liu Zhiyan , Chen Qi , Bai Lu , Wang Shaobin , Li Yongheng , Wu Hao , Yue Haizhen , Du Yi 
Published: October 2023

Abstract
Purpose
Manual clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy is pivotal but labor-intensive. This study aims to propose a deep learning (DL)-based workflow towards fully automated clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy.

Materials & methods
We retrospectively included 141 patients with Stage II-III mid-low rectal cancer and randomly grouped them into training (n = 121) and testing (n = 20) cohorts. We adopted a divide-and-conquer strategy to address CTV and GTV segmentation using two separate DL models with DpuUnet as backend-one model for CTV segmentation in the CT domain, and the other for GTV in the MRI domain. The workflow was validated using a three-level multicenter-involved blind and randomized evaluation scheme. Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) metrics were calculated in Level 1, four-grade expert scoring was performed in Level 2, and head-to-head Turing test in Level 3.

Results
For the DL-based CTV contours over the testing cohort, the DSC and 95HD (mean ± SD) were 0.85 ± 0.06 and 7.75 ± 6.42 mm respectively, and 96.4% cases achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.3%. For GTV, the DSC and 95HD were 0.87 ± 0.07 and 4.07 ± 1.67 mm respectively, and 100% of the DL-based contours achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.0%.

Conclusion
The proposed DL-based workflow exhibited promising accuracy and excellent clinical viability towards automated CTV and GTV delineation for rectal cancer neoadjuvant radiotherapy.
Changes in vital signs during adrenaline administration for hemostasis in intracordal injection: an observational study with a hypothetical design of endotracheal adrenaline administration in cardiopulmonary arrest
Authors: Hasegawa Tomohiro , Watanabe Yusuke 
Published: October 2023

Abstract
Background
The background is that intravenous adrenaline administration is recommended for advanced cardiovascular life support in adults and endotracheal administration is given low priority. The reason is that the optimal dose of adrenaline in endotracheal administration is unknown, and it is ethically difficult to design studies of endotracheal adrenaline administration with non-cardiopulmonary arrest. We otolaryngologists think so because we administered adrenaline to the vocal folds for hemostasis after intracordal injection under local anesthesia, but have had few cases of vital changes. We hypothesized that examining vital signs before and after adrenaline administration for hemostasis would help determine the optimal dose of endotracheal adrenaline.

Methods
We retrospectively examined the medical records of 79 patients who visited our hospital from January 2018 to December 2020 and received adrenaline in the vocal folds and trachea for hemostasis by intracordal injection under local anesthesia to investigate changes in heart rate and systolic blood pressure before and after the injection.

Results
The mean heart rates before and after injection were 83.96 ± 18.51 (standard deviation) beats per minute (bpm) and 81.50 ± 15.38 (standard deviation) bpm, respectively. The mean systolic blood pressure before and after the injection were 138.13 ± 25.33 (standard deviation) mmHg and 135.72 ± 22.19 (standard deviation) mmHg, respectively. Heart rate and systolic blood pressure had P-values of 0.136, and 0.450, respectively, indicating no significant differences.

Conclusions
Although this study was an observational, changes in vital signs were investigated assuming endotracheal adrenaline administration. The current recommended dose of adrenaline in endotracheal administration with cardiopulmonary arrest may not be effective. In some cases of cardiopulmonary arrest, intravenous and intraosseous routes of adrenaline administration may be difficult and the opportunity for resuscitation may be missed. Therefore, it is desirable to have many options for adrenaline administration. Therefore, if the optimal dose and efficacy of endotracheal adrenaline administration can be clarified, early adrenaline administration will be possible, which will improve return of spontaneous circulation (ROSC) and survival discharge rates.
Effects of multimodal low-opioid anesthesia protocol during on-pump coronary artery bypass grafting: a prospective cohort study
Authors: Stepan Maruniak , Oleh Loskutov , Oleksandr Druzhyna , Justyna Swol 
Published: October 2023

Abstract
Background
The most favorable anesthesia protocol during on-pump coronary artery bypass grafting (CABG) in patients with coronary heart disease remains unclear, despite previous publications regarding the interaction between anesthesia protocol and postoperative complications. The aim of the study was to compare the effect of a multimodal low-opioid anesthesia protocol (MLOP) on early postoperative complications during on-pump CABG.

Methods
A single-center prospective cohort study including 120 patients undergoing on-pump CABG aged 18 to 65 years, divided into two groups according to undergoing MLOP or routine-opioid anesthesia protocol (ROP). The analyzed parameters were plasma IL-6 levels, complications, duration of mechanical ventilation, length of intensive care unit stay, and hospitalization.

Results
In the MLOP group, the levels of IL-6 at the end of the surgery were 25.6% significantly lower compared to the ROP group (33.4 ± 9.4 vs. 44.9 ± 15.9, p < 0.0001), the duration of mechanical ventilation was significantly shorter (2.0 (2.0; 3.0) h vs. 4.0 (3.0; 5.0) h, p < 0.001), the incidence of low cardiac output syndrome was almost two and half times lower (7 (11.7%) vs. 16 (26.7%), p = 0.037), and also the incidence of postoperative atrial fibrillation was significantly lower (9 (15.0%) vs. 19 (31.7%), p = 0.031).

Conclusion
Our study confirms that using MLOP was characterized by significantly lower levels of IL-6 at the end of surgery and a lower incidence of low cardiac output syndrome and postoperative atrial fibrillation than ROP.

Trial registration
The study is registered in clinicaltrials.gov №NCT05514652.
Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment
Authors: Peroni Edoardo , Randi Maria Luigia , Rosato Antonio , Cagnin Stefano 
Published: October 2023

AbstractAcute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard “one size fits all” treatment approach included intensive chemotherapy treatment with anthracyclines and cytarabine.The manuscript first traces the evolution of the understanding of the pathology from the 1970s to the present. The enormous strides made in its categorization prove to be crucial for risk stratification, enabling an increasingly personalized diagnosis and treatment approach.Subsequently, we highlight how, over the past 15 years, technological advances enabling single cell RNA sequencing and T-cell modification based on the genomic tools are affecting the classification and treatment of AML. At the dawn of the new millennium, the advent of high-throughput next-generation sequencing technologies has enabled the profiling of patients evidencing different facets of the same disease, stratifying risk, and identifying new possible therapeutic targets that have subsequently been validated. Currently, the possibility of investigating tumor heterogeneity at the single cell level, profiling the tumor at the time of diagnosis or after treatments exist. This would allow the identification of underrepresented cellular subclones or clones resistant to therapeutic approaches and thus responsible for post-treatment relapse that would otherwise be difficult to detect with bulk investigations on the tumor biopsy. Single-cell investigation will then allow even greater personalization of therapy to the genetic and transcriptional profile of the tumor, saving valuable time and dangerous side effects. The era of personalized medicine will take a huge step forward through the disclosure of each individual piece of the complex puzzle that is cancer pathology, to implement a “tailored” therapeutic approach based also on engineered CAR-T cells.
The therapeutic landscape of tauopathies: challenges and prospects
Authors: Cummings Jeffrey L. , Gonzalez M. Isabel , Pritchard Martyn C. , May Patrick C. , Toledo-Sherman Leticia M. , Harris Glenn A. 
Published: October 2023

AbstractTauopathies are a group of neurodegenerative disorders characterized by the aggregation of the microtubule-associated protein tau. Aggregates of misfolded tau protein are believed to be implicated in neuronal death, which leads to a range of symptoms including cognitive decline, behavioral change, dementia, and motor deficits. Currently, there are no effective treatments for tauopathies. There are four clinical candidates in phase III trials and 16 in phase II trials. While no effective treatments are currently approved, there is increasing evidence to suggest that various therapeutic approaches may slow the progression of tauopathies or improve symptoms. This review outlines the landscape of therapeutic drugs (indexed through February 28, 2023) that target tau pathology and describes drug candidates in clinical development as well as those in the discovery and preclinical phases. The review also contains information on notable therapeutic programs that are inactive or that have been discontinued from development.