bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situ chemoimmunotherapy hydrogel elicits immunogenic cell death and evokes efficient antitumor immune response
Authors: Liu Qin , Xu Rui , Shen Jingwen , Tao Yaping , Shao Jingyi , Ke Yaohua , Liu Baorui 
Published: April 2024

Abstract
Background
Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application.

Methods
Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated.

Results
This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses.

Conclusions
Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.
Expression of the SARS-CoV-2 receptor-binding domain by live attenuated influenza vaccine virus as a strategy for designing a bivalent vaccine against COVID-19 and influenza
Authors: Stepanova Ekaterina , Isakova-Sivak Irina , Mezhenskaya Daria , Niskanen Sergei , Matyushenko Victoria , Bazhenova Ekaterina , Rak Alexandra , Wong Pei Fong , Prokopenko Polina , Kotomina Tatiana , Krutikova Elena , Legotskiy Sergei , Neterebskii Bogdan , Ostroukhova Tatiana , Sivak Konstantin , Orshanskaya Yana , Yakovlev Kirill , Rudenko Larisa 
Published: April 2024

AbstractInfluenza and SARS-CoV-2 are two major respiratory pathogens that cocirculate in humans and cause serious illness with the potential to exacerbate disease in the event of co-infection. To develop a bivalent vaccine, capable of protecting against both infections, we inserted the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein into hemagglutinin (HA) molecule or into the open reading frame of the truncated nonstructural protein 1 (NS1) of live attenuated influenza vaccine (LAIV) virus and assessed phenotypic characteristics of the rescued LAIV-RBD viruses, as well as their immunogenicity in mouse and Syrian hamster animal models. A panel of 9 recombinant LAIV-RBD viruses was rescued using the A/Leningrad/17 backbone. Notably, only two variants with RBD insertions into the HA molecule could express sufficient quantities of RBD protein in infected MDCK cells. Intranasal immunization of mice induced high levels of anti-influenza antibody responses in all chimeric LAIV-RBD viruses, which was comparable to the LAIV virus vector. The RBD-specific antibody responses were most pronounced in the variant expressing RBD194 fragment as a chimeric HA protein. This candidate was further tested in Syrian hamsters and was shown to be immunogenic and capable of protecting animals against both infections.
Body composition and body fat distribution in tissue-specific insulin resistance and in response to a 12-week isocaloric dietary macronutrient intervention
Authors: Trouwborst Inez , Jardon Kelly M. , Gijbels Anouk , Hul Gabby , Feskens Edith J.M. , Afman Lydia A. , Linge Jennifer , Goossens Gijs H. , Blaak Ellen E. 
Published: April 2024

Abstract
Background
Body composition and body fat distribution are important predictors of cardiometabolic diseases. The etiology of cardiometabolic diseases is heterogenous, and partly driven by inter-individual differences in tissue-specific insulin sensitivity.

Objectives
To investigate (1) the associations between body composition and whole-body, liver and muscle insulin sensitivity, and (2) changes in body composition and insulin sensitivity and their relationship after a 12-week isocaloric diet high in mono-unsaturated fatty acids (HMUFA) or a low-fat, high-protein, high-fiber (LFHP) diet.

Methods
This subcohort analysis of the PERSON study includes 93 individuals (53% women, BMI 25–40 kg/m2, 40–75 years) who participated in this randomized intervention study. At baseline and after 12 weeks of following the LFHP, or HMUFA diet, we performed a 7-point oral glucose tolerance test to assess whole-body, liver, and muscle insulin sensitivity, and whole-body magnetic resonance imaging to determine body composition and body fat distribution. Both diets are within the guidelines of healthy nutrition.

Results
At baseline, liver fat content was associated with worse liver insulin sensitivity (β [95%CI]; 0.12 [0.01; 0.22]). Only in women, thigh muscle fat content was inversely related to muscle insulin sensitivity (-0.27 [-0.48; -0.05]). Visceral adipose tissue (VAT) was inversely associated with whole-body, liver, and muscle insulin sensitivity. Both diets decreased VAT, abdominal subcutaneous adipose tissue (aSAT), and liver fat, but not whole-body and tissue-specific insulin sensitivity with no differences between diets. Waist circumference, however, decreased more following the LFHP diet as compared to the HMUFA diet (-3.0 vs. -0.5 cm, respectively). After the LFHP but not HMUFA diet, improvements in body composition were positively associated with improvements in whole-body and liver insulin sensitivity.

Conclusions
Liver and muscle insulin sensitivity are distinctly associated with liver and muscle fat accumulation. Although both LFHP and HMUFA diets improved in body fat, VAT, aSAT, and liver fat, only LFHP-induced improvements in body composition are associated with improved insulin sensitivity.

Trial registration
NCT03708419 (clinicaltrials.gov).
Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial
Authors: Johnson Christina , Chen Jinbo , McGowan Mary P. , Tricou Eric , Card Mary , Pettit Amy R. , Klaiman Tamar , Rader Daniel J. , Volpp Kevin G. , Beidas Rinad S. 
Published: April 2024

Abstract
Background
Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science—including mixed-methods contextual inquiry with clinicians, patients, and health system constituents—to co-design two patient-facing implementation strategies to address this care gap: (a) an automated health system-mediated strategy and (b) a nonprofit foundation-mediated strategy with contact from a foundation-employed care navigator. This trial will test the comparative effectiveness of these strategies on completion of cascade screening for relatives of individuals with FH, centering equitable reach.

Methods
We will conduct a hybrid effectiveness-implementation type III randomized controlled trial testing the comparative effectiveness of two strategies for implementing cascade screening with 220 individuals with FH (i.e., probands) per arm identified from a large northeastern health system. The primary implementation outcome is reach, or the proportion of probands with at least one first-degree biological relative (parent, sibling, child) in the USA who is screened for FH through the study. Our secondary implementation outcomes include the number of relatives screened and the number of relatives meeting the American Heart Association criteria for FH. Our secondary clinical effectiveness outcome is post-trial proband cholesterol level. We will also use mixed methods to identify implementation strategy mechanisms for implementation strategy effectiveness while centering equity.

Discussion
We will test two patient-facing implementation strategies harnessing insights from behavioral economics that were developed collaboratively with constituents. This trial will improve our understanding of how to implement evidence-based cascade screening for FH, which implementation strategies work, for whom, and why. Learnings from this trial can be used to equitably scale cascade screening programs for FH nationally and inform cascade screening implementation efforts for other genetic disorders.

Trial registration
ClinicalTrials.gov, NCT05750667. Registered 15 February 2023—retrospectively registered, https://clinicaltrials.gov/study/NCT05750667.
The socioeconomic epidemiology of inherited retinal diseases in Portugal
Authors: Marta Ana , Marques João Pedro , Santos Cristina , Coutinho-Santos Luísa , Vaz-Pereira Sara , Costa José , Arede Pedro , Félix Raquel , Geada Sara , Gouveia Nuno , Silva Rui , Baptista Margarida , Lume Miguel , Parreira Ricardo , Azevedo Soares Célia , Menéres Maria João , Lemos Carolina , Melo Beirão João 
Published: April 2024

Abstract
Background
Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures.

Results
This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001).

Conclusion
The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.
Cerebral venous congestion alters CNS homeostatic plasticity, evoking tinnitus-like behavior
Authors: Wei Huimin , Jiang Huimin , Zhou Yifan , Liu Lu , Ma Wei , Ni Shanshan , Zhou Chen , Ji Xunming 
Published: April 2024

Abstract
Background
Brain function and neuronal activity depend on a constant supply of blood from the cerebral circulation. The cerebral venous system (CVS) contains approximately 70% of the total cerebral blood volume; similar to the cerebral arterial system, the CVS plays a prominent role in the maintenance of central nervous system (CNS) homeostasis. Impaired venous autoregulation, which can appear in forms such as cerebral venous congestion, may lead to metabolic abnormalities in the brain, causing severe cerebral functional defects and even chronic tinnitus. However, the role of cerebral venous congestion in the progression of tinnitus is underrecognized, and its pathophysiology is still incompletely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in the onset and persistence of tinnitus and the possible neurophysiological mechanisms.

Results
We found that a rat model of cerebral venous congestion exhibited tinnitus-like behavioral manifestations at 14 days postoperatively; from that point onward, they showed signs of persistent tinnitus without significant hearing impairment. Subsequent neuroimaging and neurochemical findings showed CNS homeostatic plasticity disturbance in rats with cerebral venous congestion, reflected in increased neural metabolic activity, ultrastructural synaptic changes, upregulated synaptic efficacy, reduced inhibitory synaptic transmission (due to GABA deficiency), and elevated expression of neuroplasticity-related proteins in central auditory and extra-auditory pathways.

Conclusion
Collectively, our data suggest that alternations in CNS homeostatic plasticity may play a vital role in tinnitus pathology caused by cerebral venous congestion. These findings provide a new perspective on tinnitus related to cerebral venous congestion and may facilitate the development of precise interventions to interrupt its pathogenesis.
Association of socioeconomic deprivation with outcomes in critically ill adult patients: an observational prospective multicenter cohort study
Authors: Benaïs Morgan , Duprey Matthieu , Federici Laura , Arnaout Michel , Mora Pierre , Amouretti Marc , Bourgeon-Ghittori Irma , Gaudry Stéphane , Garçon Pierre , Reuter Danielle , Geri Guillaume , Megarbane Bruno , Lebut Jordane , Mekontso-Dessap Armand , Ricard Jean-Damien , da Silva Daniel , de Montmollin Etienne 
Published: April 2024

Abstract
Background
The influence of socioeconomic deprivation on health inequalities is established, but its effect on critically ill patients remains unclear, due to inconsistent definitions in previous studies.

Methods
Prospective multicenter cohort study conducted from March to June 2018 in eight ICUs in the Greater Paris area. All admitted patients aged ≥ 18 years were enrolled. Socioeconomic phenotypes were identified using hierarchical clustering, based on education, health insurance, income, and housing. Association of phenotypes with 180-day mortality was assessed using Cox proportional hazards models.

Results
A total of 1,748 patients were included. Median age was 62.9 [47.4–74.5] years, 654 (37.4%) patients were female, and median SOFA score was 3 [1–6]. Study population was clustered in five phenotypes with increasing socioeconomic deprivation. Patients from phenotype A (n = 958/1,748, 54.8%) were without socioeconomic deprivation, patients from phenotype B (n = 273/1,748, 15.6%) had only lower education levels, phenotype C patients (n = 117/1,748, 6.7%) had a cumulative burden of 1[1–2] deprivations and all had housing deprivation, phenotype D patients had 2 [1–2] deprivations, all of them with income deprivation, and phenotype E patients (n = 93/1,748, 5.3%) included patients with 3 [2–4] deprivations and included all patients with health insurance deprivation. Patients from phenotypes D and E were younger, had fewer comorbidities, more alcohol and opiate use, and were more frequently admitted due to self-harm diagnoses. Patients from phenotype C (predominant housing deprivation), were more frequently admitted with diagnoses related to chronic respiratory diseases and received more non-invasive positive pressure ventilation. Following adjustment for age, sex, alcohol and opiate use, socioeconomic phenotypes were not associated with increased 180-day mortality: phenotype A (reference); phenotype B (hazard ratio [HR], 0.85; 95% confidence interval CI 0.65–1.12); phenotype C (HR, 0.56; 95% CI 0.34–0.93); phenotype D (HR, 1.09; 95% CI 0.78–1.51); phenotype E (HR, 1.20; 95% CI 0.73–1.96).

Conclusions
In a universal health care system, the most deprived socioeconomic phenotypes were not associated with increased 180-day mortality. The most disadvantaged populations exhibit distinct characteristics and medical conditions that may be addressed through targeted public health interventions.
Patient characteristics of, and remedial interventions for, complaints and medico-legal claims against doctors: a rapid review of the literature
Authors: Schultz Timothy J. , Zhou Michael , Gray Jodi , Roseleur Jackie , Clark Richard , Mordaunt Dylan A. , Hibbert Peter D. , Haysom Georgie , Wright Michael 
Published: April 2024

Abstract
Background
It is uncertain if patient’s characteristics are associated with complaints and claims against doctors. Additionally, evidence for the effectiveness of remedial interventions on rates of complaints and claims against doctors has not been synthesised.

Methods
We conducted a rapid review of recent literature to answer: Question 1 “What are the common characteristics and circumstances of patients who are most likely to complain or bring a claim about the care they have received from a doctor?” and Question 2 “What initiatives or interventions have been shown to be effective at reducing complaints and claims about the care patients have received from a doctor?”. We used a systematic search (most recently in July 2023) of PubMed, Scopus, Web of Science and grey literature. Studies were screened against inclusion criteria and critically appraised in duplicate using standard tools. Results were summarised using narrative synthesis.

Results
From 8079 search results, we reviewed the full text of 250 studies. We included 25 studies: seven for Question 1 (6 comparative studies with controls and one systematic review) and 18 studies for Question 2 (14 uncontrolled pre-post studies, 2 comparative studies with controls and 2 systematic reviews). Most studies were set in hospitals across a mix of medical specialties.
Other than for patients with mental health conditions (two studies), no other patient characteristics demonstrated either a strong or consistent effect on the rate of complaints or claims against their treating doctors.
Risk management programs (6 studies), and communication and resolution programs (5 studies) were the most studied of 6 intervention types. Evidence for reducing complaints and medico-legal claims, costs or premiums and more timely management was apparent for both types of programs. Only 1 to 3 studies were included for peer programs, medical remediation, shared decision-making, simulation training and continuing professional development, with few generalisable results.

Conclusion
Few patient characteristics can be reliably related to the likelihood of medico-legal complaints or claims. There is some evidence that interventions can reduce the number and costs of claims, the number of complaints, and the timeliness of claims. However, across both questions, the strength of the evidence is very weak and is based on only a few studies or study designs that are highly prone to bias.
The Functional-Cognitive and Sensory Treatment (F-CaST) to improve rehabilitation outcomes of individuals with substance use disorder: a study protocol for a mixed-method randomized controlled trial
Authors: Assayag Naama , Bar-Shalita Tami , Rand Debbie 
Published: April 2024

Abstract
Background
Substance use disorder (SUD) is associated with executive function (EF) deficits and sensory modulation dysfunction (SMD). Yet, these deficits are not addressed therapeutically. This study aims to examine the effectiveness of the Functional-Cognitive and Sensory Treatment (F-CaST) compared to standard care to improve everyday performance and behavior and length of stay at the therapeutic community (TC) in individuals with SUD. In addition, to assess the improvement in EF, sensory modulation, participation, self-efficacy, life satisfaction, and use of strategies within and between groups. Satisfaction with F-CaST will also be assessed.

Methods
Forty-eight participants from a community of men in a TC, aged 18–45 years will be randomly allocated to (i) F-CaST—(experimental group) providing sensory and EF strategies for improving daily function; (ii) standard care (control group) as provided in the TC. Assessments will be conducted by assessors blind to group allocation at 4 time points: T1- pre-intervention; T2- post-intervention; T3- 1-month follow-up; and T4- 3-month follow-up. Primary outcome measures will be everyday performance, assessed by the Canadian Occupational Performance Measure (COPM), behavior and length of stay in the TC; secondary outcome measures will assess EF, SMD. Semi-structured in-depth qualitative interviews will be conducted at T1, T2 and T4.

Discussion
We hypothesize that F-CaST will lead to improved everyday performance and longer length of stay in the TC, compared to the control group. If F-CaST will prove to be effective, cognitive and sensory strategies may be incorporated as an adjunctive intervention in SUD rehabilitation.
Trial registration: ClinicalTrials.gov NCT05647863 Registered on 13 December 2022, https://classic.clinicaltrials.gov/ct2/show/NCT05647863.
Targeting ferroptosis for leukemia therapy: exploring novel strategies from its mechanisms and role in leukemia based on nanotechnology
Authors: Ashoub Muhammad Hossein , Razavi Razieh , Heydaryan Kamran , Salavati-Niasari Masoud , Amiri Mahnaz 
Published: April 2024

AbstractThe latest findings in iron metabolism and the newly uncovered process of ferroptosis have paved the way for new potential strategies in anti-leukemia treatments. In the current project, we reviewed and summarized the current role of nanomedicine in the treatment and diagnosis of leukemia through a comparison made between traditional approaches applied in the treatment and diagnosis of leukemia via the existing investigations about the ferroptosis molecular mechanisms involved in various anti-tumor treatments. The application of nanotechnology and other novel technologies may provide a new direction in ferroptosis-driven leukemia therapies. The article explores the potential of targeting ferroptosis, a new form of regulated cell death, as a new therapeutic strategy for leukemia. It discusses the mechanisms of ferroptosis and its role in leukemia and how nanotechnology can enhance the delivery and efficacy of ferroptosis-inducing agents. The article not only highlights the promise of ferroptosis-targeted therapies and nanotechnology in revolutionizing leukemia treatment, but also calls for further research to overcome challenges and fully realize the clinical potential of this innovative approach. Finally, it discusses the challenges and opportunities in clinical applications of ferroptosis.