bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of dietary carbohydrate and calorie restriction on weight and metabolic health in overweight/obese individuals: a multi-center randomized controlled trial
Authors: Sun Jia , Ruan Yuting , Xu Ningning , Wu Peili , Lin Nie , Yuan Kun , An Shengli , Kang Pei , Li Shu , Huang Qiya , Yingzhang  , Li Yuzhong , Su Jialin , Ma Wenjun , Chen Bo , Zhang Xiuwei , Chen Xiaoming , Liang Yongqian , Lu Zeyuan , Deng Guobao , Zhang Zhen , Wang Yuqin , Wen Weiheng , Zhang Huijie , Chen Hong 
Published: May 2023

Abstract
Background
Both low‐carbohydrate (LC) and calorie-restricted (CR) diets have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a 12-week randomized trial to compare the effects of these diets separately and in combination on both weight loss and metabolic risk factors in overweight/obese individuals.

Methods
A total of 302 participants were randomized to LC diet (n = 76), CR diet (n = 75), LC + CR diet (n = 76), or normal control (NC) diet (n = 75) using a computer-based random number generator. The primary outcome was the change in body mass index (BMI). The secondary outcomes included body weight, waist circumference, waist-to-hip ratio, body fat, and metabolic risk factors. All participants attended health education sessions during the trial.

Results
A total of 298 participants were analyzed. BMI change over 12 weeks was − 0.6 (95% CI, − 0.8 to − 0.3) kg/m2 in NC, − 1.3 (95% CI, − 1.5 to − 1.1) kg/m2 in CR, − 2.3 (95% CI, − 2.6 to − 2.1) kg/m2 in LC, and − 2.9 (95% CI, − 3.2 to − 2.6) kg/m2 in LC + CR. LC + CR diet was more effective than LC or CR diet alone at reducing BMI (P = 0.001 and P < 0.001, respectively). Furthermore, compared with the CR diet, the LC + CR diet and LC diet further reduced body weight, waist circumference, and body fat. Serum triglycerides were significantly reduced in the LC + CR diet group compared with the LC or CR diet alone. Plasma glucose, homeostasis model assessment of insulin resistance, and cholesterol concentrations (total, LDL, and HDL) did not change significantly between the groups during the 12-week intervention.

Conclusions
The reduction of carbohydrate intake without restricting caloric intake is more potent to achieve weight loss over 12 weeks when compared to a calorie-restricted diet in overweight/obese adults. The combination of restricting carbohydrate and total calorie intake may augment the beneficial effects of reducing BMI, body weight, and metabolic risk factors among overweight/obese individuals.

Trial registration
The study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center (registration number: ChiCTR1800015156).
Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review
Authors: Maksoud Rebekah , Magawa Chandi , Eaton-Fitch Natalie , Thapaliya Kiran , Marshall-Gradisnik Sonya 
Published: May 2023

Abstract
Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifaceted condition that affects most body systems. There is currently no known diagnostic biomarker; instead, diagnosis is dependent on application of symptom-based case criteria following exclusion of any other potential medical conditions. While there are some studies that report potential biomarkers for ME/CFS, their efficacy has not been validated. The aim of this systematic review is to collate and appraise literature pertaining to a potential biomarker(s) which may effectively differentiate ME/CFS patients from healthy controls.

Methods
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane review guidelines. PubMed, Embase and Scopus were systematically searched for articles containing “biomarker” and “ME/CFS” keywords in the abstract or title and if they included the following criteria: (1) were observational studies published between December 1994 and April 2022; (2) involved adult human participants; (3) full text is available in English (4) original research; (5) diagnosis of ME/CFS patients made according to the Fukuda criteria (1994), Canadian Consensus Criteria (2003), International Consensus Criteria (2011) or Institute of Medicine Criteria (2015); (6) study investigated potential biomarkers of ME/CFS compared to healthy controls. Quality and Bias were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.

Results
A total of 101 publications were included in this systematic review. Potential biomarkers ranged from genetic/epigenetic (19.8%), immunological (29.7%), metabolomics/mitochondrial/microbiome (14.85%), endovascular/circulatory (17.82%), neurological (7.92%), ion channel (8.91%) and physical dysfunction biomarkers (8.91%). Most of the potential biomarkers reported were blood-based (79.2%). Use of lymphocytes as a model to investigate ME/CFS pathology was prominent among immune-based biomarkers. Most biomarkers had secondary (43.56%) or tertiary (54.47%) selectivity, which is the ability for the biomarker to identify a disease-causing agent, and a moderate (59.40%) to complex (39.60%) ease-of-detection, including the requirement of specialised equipment.

Conclusions
All potential ME/CFS biomarkers differed in efficiency, quality, and translatability as a diagnostic marker. Reproducibility of findings between the included publications were limited, however, several studies validated the involvement of immune dysfunction in the pathology of ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of illness. The heterogeneity shown across many of the included studies highlights the need for multidisciplinary research and uniform protocols in ME/CFS biomarker research.
A combination of genetically engineered oncolytic virus and melittin-CpG for cancer viro-chemo-immunotherapy
Authors: Bahreyni Amirhossein , Liu Huitao , Mohamud Yasir , Xue Yuan Chao , Fan Yiyun Michelle , Zhang Yizhuo Lyanne , Luo Honglin 
Published: May 2023

Abstract
Background
Immunotherapy has emerged as an efficient therapeutic approach for cancer management. However, stimulation of host immune system against cancer cells often fails to achieve promising clinical outcomes mainly owing to the immunosuppressive characteristics of the tumor microenvironment (TME). Combination therapeutics that can trigger sustained immunogenic cell death (ICD) have provided new opportunities for cancer treatment.

Methods
In this study, we designed and applied an ICD inducer regimen, including a genetically engineered oncolytic virus (miRNA-modified coxsackieviruses B3, miR-CVB3), a pore-forming lytic peptide (melittin, found in bee venom), and a synthetic toll-like receptor 9 ligand (CpG oligodeoxynucleotides), for breast cancer and melanoma treatment. We compared the anti-tumor efficacy of miR-CVB3 and CpG-melittin (CpGMel) alone and in combination (miR-CVB3 + CpGMel) and investigated possible mechanisms involved.

Results
We demonstrated that miR-CVB3 + CpGMel had no major impact on viral growth, while enhancing the cellular uptake of CpGMel in vitro. We further showed that combination therapy led to significant increases in tumor cell death and release of damage-associated molecular patterns compared with individual treatment. In vivo studies in 4T1 tumor-bearing Balb/c mice revealed that both primary and distant tumors were significantly suppressed, and the survival rate was significantly prolonged after administration of miR-CVB3 + CpGMel compared with single treatment. This anti-tumor effect was accompanied by increased ICD and immune cell infiltration into the TME. Safety analysis showed no significant pathological abnormalities in Balb/c mice. Furthermore, the developed therapeutic regimen also demonstrated a great anti-tumor activity in B16F10 melanoma tumor-bearing C57BL/6 J mice.

Conclusions
Overall, our findings indicate that although single treatment using miR-CVB3 or CpGMel can efficiently delay tumor growth, combining oncolytic virus-based therapy can generate even stronger anti-tumor immunity, leading to a greater reduction in tumor size.
Cardiovascular complications of diabetes: role of non-coding RNAs in the crosstalk between immune and cardiovascular systems
Authors: Spinetti Gaia , Mutoli Martina , Greco Simona , Riccio Federica , Ben-Aicha Soumaya , Kenneweg Franziska , Jusic Amela , de Gonzalo-Calvo David , Nossent Anne Yaël , Novella Susana , Kararigas Georgios , Thum Thomas , Emanueli Costanza , Devaux Yvan , Martelli Fabio 
Published: May 2023

AbstractDiabetes mellitus, a group of metabolic disorders characterized by high levels of blood glucose caused by insulin defect or impairment, is a major risk factor for cardiovascular diseases and related mortality. Patients with diabetes experience a state of chronic or intermittent hyperglycemia resulting in damage to the vasculature, leading to micro- and macro-vascular diseases. These conditions are associated with low-grade chronic inflammation and accelerated atherosclerosis. Several classes of leukocytes have been implicated in diabetic cardiovascular impairment. Although the molecular pathways through which diabetes elicits an inflammatory response have attracted significant attention, how they contribute to altering cardiovascular homeostasis is still incompletely understood. In this respect, non-coding RNAs (ncRNAs) are a still largely under-investigated class of transcripts that may play a fundamental role. This review article gathers the current knowledge on the function of ncRNAs in the crosstalk between immune and cardiovascular cells in the context of diabetic complications, highlighting the influence of biological sex in such mechanisms and exploring the potential role of ncRNAs as biomarkers and targets for treatments. The discussion closes by offering an overview of the ncRNAs involved in the increased cardiovascular risk suffered by patients with diabetes facing Sars-CoV-2 infection.Graphical Abstract
Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases
Authors: Zhu Junyan , Wang Sicong , Yang Dakai , Xu Wenrong , Qian Hui 
Published: May 2023

AbstractExtracellular vesicles (EVs), a cluster of cell-secreted lipid bilayer nanoscale particles, universally exist in body fluids, as well as cell and tissue culture supernatants. Over the past years, increasing attention have been paid to the important role of EVs as effective intercellular communicators in fibrotic diseases. Notably, EV cargos, including proteins, lipids, nucleic acids, and metabolites, are reported to be disease-specific and can even contribute to fibrosis pathology. Thus, EVs are considered as effective biomarkers for disease diagnosis and prognosis. Emerging evidence shows that EVs derived from stem/progenitor cells have great prospects for cell-free therapy in various preclinical models of fibrotic diseases and engineered EVs can improve the targeting and effectiveness of their treatment. In this review, we will focus on the biological functions and mechanisms of EVs in the fibrotic diseases, as well as their potential as novel biomarkers and therapeutic strategies.
Food availability positively affects the survival and somatic maintenance of hibernating garden dormice (Eliomys quercinus)
Authors: Giroud Sylvain , Ragger Marie-Therese , Baille Amélie , Hoelzl Franz , Smith Steve , Nowack Julia , Ruf Thomas 
Published: May 2023

Abstract
Background
Torpor is an energy saving strategy achieved by substantial reductions of metabolic rate and body temperature that enables animals to survive periods of low resource availability. During hibernation (multiday torpor), the frequency of periodic rewarming—characterised by high levels of oxidative stress—is associated with shortening of telomeres, a marker of somatic maintenance.

Objectives
In this study, we determined the impact of ambient temperature on feeding behaviour and telomere dynamics in hibernating garden dormice (Eliomys quercinus) over winter. This obligate hibernator prepares for hibernation by accumulating fat stores but can also feed during hibernation.

Methodology
Food intake, torpor pattern, changes in telomere length, and body mass change were assessed in animals housed at experimentally controlled temperatures of either 14 °C (i.e., a mild winter) or 3 °C (i.e., a cold winter) over 6 months.

Results
When hibernating at 14 °C, dormice experienced 1.7-fold more frequent and 2.4-fold longer inter-bout euthermia, and spent significantly less time torpid, compared to animals hibernating at 3 °C. Higher food intake enabled individuals to compensate for increased energetic costs when hibernating at milder temperatures (14 °C vs. 3 °C), to buffer body mass loss and thus increase winter survival. Interestingly, we observed a significant increase of telomere length over the entire hibernation period, irrespective of temperature treatment.

Conclusion
We conclude that higher temperatures during winter, if associated with sufficient food availability, can have a positive effect on the individual’s energy balance and somatic maintenance. These results suggest that winter food availability might be a crucial determinant for the survival of the garden dormouse in the context of ever-increasing environmental temperatures.
Oleoylethanolamide attenuates cocaine-primed reinstatement and alters dopaminergic gene expression in the striatum
Authors: González-Portilla Macarena , Mellado Susana , Montagud-Romero Sandra , Rodríguez de Fonseca Fernando , Pascual María , Rodríguez-Arias Marta 
Published: May 2023

AbstractThe lipid oleoylethanolamide (OEA) has been shown to affect reward-related behavior. However, there is limited experimental evidence about the specific neurotransmission systems OEA may be affecting to exert this modulatory effect. The aim of this study was to evaluate the effects of OEA on the rewarding properties of cocaine and relapse-related gene expression in the striatum and hippocampus. For this purpose, we evaluated male OF1 mice on a cocaine-induced CPP procedure (10 mg/kg) and after the corresponding extinction sessions, we tested drug-induced reinstatement. The effects of OEA (10 mg/kg, i.p.) were evaluated at three different timepoints: (1) Before each cocaine conditioning session (OEA-C), (2) Before extinction sessions (OEA-EXT) and (3) Before the reinstatement test (OEA-REINST). Furthermore, gene expression changes in dopamine receptor D1 gene, dopamine receptor D2 gene, opioid receptor µ, cannabinoid receptor 1, in the striatum and hippocampus were analyzed by qRT-PCR. The results obtained in the study showed that OEA administration did not affect cocaine CPP acquisition. However, mice receiving different OEA treatment schedules (OEA-C, OEA-EXT and OEA-REINST) failed to display drug-induced reinstatement. Interestingly, the administration of OEA blocked the increase of dopamine receptor gene D1 in the striatum and hippocampus caused by cocaine exposure. In addition, OEA-treated mice exhibited reduced striatal dopamine receptor gene D2 and cannabinoid receptor 1. Together, these findings suggest that OEA may be a promising pharmacological agent in the treatment of cocaine use disorder.
Reconciling art and science in the era of personalised medicine: the legacy of Georges Canguilhem
Authors: Contino Gianmarco 
Published: May 2023

Abstract
Background
Biomedicine, i.e. the application of basic sciences to medicine, has become the cornerstone for the study of etiopathogenesis and treatment of diseases. Biomedicine has enormously contributed to the progress of medicine and healthcare and has become the preferred approach to medical problems in the West. The developments in statistical inference and machine learning techniques have provided the foundation for personalised medicine where clinical management can be fully informed by biomedicine. The deployment of precision medicine may impact the autonomy and self-normativity of the patients. Understanding the relationship between biomedicine and medical practice can help navigate the benefits and challenges offered by precision medicine.

Methods
Conventional content analysis was applied to “Le Normal and le Pathologique” (Canguilhem G. The Normal and the Pathological. Princeton: Princeton University Press; 1991) and further investigated with respect to its relationship with techne and precision medicine using PubMed and Google Scholar and the Standford Encyclopedia of Philosophy to search for the following keywords singularly or in combination: “Canguilhem”, “techne”, “episteme”, “precision medicine”, “machine learning AND medicine”.

Results
The Hippocratic concept of techne accounts for many characteristics of medical knowledge and practice. The advances of biomedicine, experimental medicine and, more recently, machine learning offer, in contrast, the model of a medicine based purely on episteme. I argue that Canguilhem medical epistemology establishes a framework where episteme and data-driven medicine is compatible with the promotion of patient’s autonomy and self-normativity.

Conclusions
Canguilhem’s medical epistemology orders the relationship of applied medicine with experimental sciences, ethics and social sciences. It provides guidance to define the scope of medicine and the boundaries of medicalization of healthy life. Finally, it sets an agenda for a safe implementation of machine learning in medicine.
Scaling up an intervention to protect preterm infants from neurodevelopmental disabilities — findings from a qualitative process evaluation comparing standard with enhanced quality improvement support packages for maternity units in England
Authors: Redwood Sabi , Pithara-McKeown Christalla , Stone Tracey , Treloar Emma , Donovan Jenny L. , Luyt Karen 
Published: May 2023

Abstract

Background
A quality improvement strategy (PReCePT) was used in a standard and enhanced format to scale up a clinical intervention (administering magnesium sulphate to women in preterm labour) across all maternity units in England to protect prematurely born infants from neurodevelopmental disabilities. Formal evaluations reported the effectiveness of the standard package alone in increasing the administration of magnesium sulphate. In this paper, we focus on the findings of the process evaluations, using normalisation process theory to explain how different implementation contexts generated the observed outcomes relating to normative and relational restructuring and sustainment.

Methods
Interviews were conducted with key individuals in implementation of leadership positions nationally and locally. Interviews were analysed initially using the framework method. We then engaged recursively with NPT constructs to generate generalisable insights with pragmatic applicability in other settings.

Results
In total, 72 interviews were conducted with good representation from units across England and staff from the National Academic Health Science Network. We found that all units irrespective of whether they received a standard or enhanced QI package were successful in the ‘normative restructuring’ of their setting to enable magnesium sulphate to be administered. This suggests that this implementation outcome is necessary to achieve improvements. However, it may not be sufficient to sustain the changes once additional resources have been withdrawn. Sustainment, our findings suggest, required ‘relational restructuring’ to accommodate altered workflows and facilitate the sharing of responsibilities and tasks in daily practice. Relational restructuring was more likely to have been achieved units receiving enhanced QI support but also happened in units with standard QI support, especially in those where perinatal team working was already well established.

Conclusion
Unlike other large QI-focused spread-and-scale programmes which failed to show any impact on outcomes, the PReCePT programme in both the enhanced and standard support packages led to improvements in the uptake of magnesium sulphate. The findings suggest that QI programmes interact with the enabling factors, such as strong interprofessional team working, already present in the setting. A standard package with minimal support was therefore sufficient in settings with enabling factors, but enhanced support was required in units where these were absent.
Improving the efficacy of combined radiotherapy and immunotherapy: focusing on the effects of radiosensitivity
Authors: Gao Zhiru , Zhao Qian , Xu Yiyue , Wang Linlin 
Published: May 2023

AbstractCancer treatment is gradually entering an era of precision, with multitude studies in gene testing and immunotherapy. Tumor cells can be recognized and eliminated by the immune system through the expression of tumor-associated antigens, but when the cancer escapes or otherwise suppresses immunity, the balance between cancer cell proliferation and immune-induced cancer cell killing may be interrupted, resulting in tumor proliferation and progression. There has been significant attention to combining conventional cancer therapies (i.e., radiotherapy) with immunotherapy as opposed to treatment alone. The combination of radio-immunotherapy has been demonstrated in both basic research and clinical trials to provide more effective anti-tumor responses. However, the absolute benefits of radio-immunotherapy are dependent on individual characteristics and not all patients can benefit from radio-immunotherapy. At present, there are numerous articles about exploring the optimal models for combination radio-immunotherapy, but the factors affecting the efficacy of the combination, especially with regard to radiosensitivity remain inconclusive. Radiosensitivity is a measure of the response of cells, tissues, or individuals to ionizing radiation, and various studies have shown that the radiosensitivity index (RSI) will be a potential biomarker for predicting the efficacy of combination radio-immunotherapy. The purpose of this review is to focus on the factors that influence and predict the radiosensitivity of tumor cells, and to evaluate the impact and predictive significance of radiosensitivity on the efficacy of radio-immunotherapy combination.