bluuebunny/crossref_metadata_2025 huggingface dataset:
Redox state and metabolic responses to severe heat stress in lenok Brachymystax lenok (Salmonidae)
Authors: Chen Yan , Pan Zhe , Bai Yucen , Xu Shaogang
Published: May 2023

In order to provide new insights into the physiological responses of lenok (Brachymystax lenok: Salmonidae) to acute and severe heat stress (25°C, 48 h), dynamic changes in redox state and metabolic responses are studied combined biochemical index and non-targeted metabolome. Nicotinamide adenine dinucleotide (NAD+) consumption causes significant increases in ratio of reduced NADH to NAD+ and ratio of reduced nicotinamide adenine dinucleotide phosphate (NADPH) to NADP+, which induced the redox imbalance in heat stressed lenok. Lowered reduced glutathione/oxidized glutathione (GSH/GSSG) ratios suggested that more oxidized conditions occurred in heat-stressed lenok, leading to membrane lipid oxidation. The first few hours of heat stress promoted the activity of enzymes involved in anaerobic glycolysis (hexokinase, pyruvate kinase, lactic dehydrogenase) and glutamicpyruvic transaminase and glutamic oxaloacetic transaminase, which might lead to consumption of many carbohydrates and amino acid catabolism. These enzyme activities decreased with time in a possible compensatory strategy to manage anabolic and catabolic metabolism, maintaining the redox homeostasis. After 48 h of recovery, NAD+, carbohydrate levels and enzyme activities had returned to control levels, whereas many amino acids were consumed for repair and new synthesis. GSH remained at levels lower than controls, and the more oxidized conditions had not recovered, aggravating oxidative damage. Glutamic acid, glutamine, lysine and arginine may play important roles in survival of heat-stressed lenok.
Unsupervised neural network for single cell Multi-omics INTegration (UMINT): an application to health and disease
Authors: Maitra Chayan , Seal Dibyendu B. , Das Vivek , De Rajat K.
Published: May 2023

Multi-omics studies have enabled us to understand the mechanistic drivers behind complex disease states and progressions, thereby providing novel and actionable biological insights into health status. However, integrating data from multiple modalities is challenging due to high dimensionality and diverse nature of data, and noise associated with each platform. Sparsity in data, non-overlapping features and technical batch effects make the task of learning more complicated. Conventional machine learning (ML) tools are not quite effective against such data integration hazards due to their simplistic nature with less capacity. In addition, existing methods for single cell multi-omics integration are computationally expensive. Therefore, in this work, we have introduced a novel Unsupervised neural network for single cell Multi-omics INTegration (UMINT). UMINT serves as a promising model for integrating variable number of single cell omics layers with high dimensions. It has a light-weight architecture with substantially reduced number of parameters. The proposed model is capable of learning a latent low-dimensional embedding that can extract useful features from the data facilitating further downstream analyses. UMINT has been applied to integrate healthy and disease CITE-seq (paired RNA and surface proteins) datasets including a rare disease Mucosa-Associated Lymphoid Tissue (MALT) tumor. It has been benchmarked against existing state-of-the-art methods for single cell multi-omics integration. Furthermore, UMINT is capable of integrating paired single cell gene expression and ATAC-seq (Transposase-Accessible Chromatin) assays as well.
Education differentiates cognitive performance and resting state fMRI connectivity in healthy aging
Authors: Montemurro Sonia , Filippini Nicola , Ferrazzi Giulio , Mantini Dante , Arcara Giorgio , Marino Marco
Published: May 2023

Objectives

In healthy aging, the way people cope differently with cognitive and neural decline is influenced by exposure to cognitively enriching life-experiences. Education is one of them, so that in general, the higher the education, the better the expected cognitive performance in aging. At the neural level, it is not clear yet how education can differentiate resting state functional connectivity profiles and their cognitive underpinnings. Thus, with this study, we aimed to investigate whether the variable education allowed for a finer description of age-related differences in cognition and resting state FC.

Methods

We analyzed in 197 healthy individuals (137 young adults aged 20–35 and 60 older adults aged 55–80 from the publicly available LEMON database), a pool of cognitive and neural variables, derived from magnetic resonance imaging, in relation to education. Firstly, we assessed age-related differences, by comparing young and older adults. Then, we investigated the possible role of education in outlining such differences, by splitting the group of older adults based on their education.

Results

In terms of cognitive performance, older adults with higher education and young adults were comparable in language and executive functions. Interestingly, they had a wider vocabulary compared to young adults and older adults with lower education. Concerning functional connectivity, the results showed significant age- and education-related differences within three networks: the Visual-Medial, the Dorsal Attentional, and the Default Mode network (DMN). For the DMN, we also found a relationship with memory performance, which strengthen the evidence that this network has a specific role in linking cognitive maintenance and FC at rest in healthy aging.

Discussion

Our study revealed that education contributes to differentiating cognitive and neural profiles in healthy older adults. Also, the DMN could be a key network in this context, as it may reflect some compensatory mechanisms relative to memory capacities in older adults with higher education.
Association of Life's Simple 7 with mild cognitive impairment in community-dwelling older adults in China: a cross-sectional study
Authors: Yang Mengshu , Liu Yilan , Hu Xiuzhen , Ren Dianxu , Yang Qing , Mao Jing , Chen Jing
Published: May 2023

Background

Life's Simple 7 (LS7), a metric composed of seven intervenable cardiovascular risk factors, is initiated by the American Heart Association to improve cardiovascular health. The components of LS7 have been reported as risk factors for dementia. However, few studies investigated the association between LS7 metric and mild cognitive impairment (MCI).

Methods

The study was carried out in a primary care facility between 8 June and 10 July 2022. A total of 297 community-dwelling residents aged 65 years or older were recruited. Sociodemographic, comorbidity, and lifestyle characteristics were collected through the questionnaires, and biological parameters were obtained from blood sample examinations. Logistic regression was used to analyze the association between LS7 scores (overall, behavioral, and biological) and individual components with MCI, adjusting sex, age, education, and cardiovascular disease (CVD).

Results

In comparison with the cognitively intact group (n = 195), the MCI group (n = 102) had a lower education level and a higher proportion of hypertension. Multivariate logistic regression analysis, adjusting sex, age, education, and CVD demonstrated a significant association between MCI and overall LS7 score [odd ratio = 0.805, 95% confidence interval (0.690, 0.939)] and biological score [odd ratio = 0.762, 95% confidence interval (0.602, 0.965)].

Conclusion

Life's Simple 7 was associated with MCI in community-dwelling older adults, indicating that LS7 could be used as guidance in the prevention of dementia in the community.
Tackling the glial scar in spinal cord regeneration: new discoveries and future directions
Authors: Shafqat Areez , Albalkhi Ibrahem , Magableh Hamzah M. , Saleh Tariq , Alkattan Khaled , Yaqinuddin Ahmed
Published: May 2023

Axonal regeneration and functional recovery are poor after spinal cord injury (SCI), typified by the formation of an injury scar. While this scar was traditionally believed to be primarily responsible for axonal regeneration failure, current knowledge takes a more holistic approach that considers the intrinsic growth capacity of axons. Targeting the SCI scar has also not reproducibly yielded nearly the same efficacy in animal models compared to these neuron-directed approaches. These results suggest that the major reason behind central nervous system (CNS) regeneration failure is not the injury scar but a failure to stimulate axon growth adequately. These findings raise questions about whether targeting neuroinflammation and glial scarring still constitute viable translational avenues. We provide a comprehensive review of the dual role of neuroinflammation and scarring after SCI and how future research can produce therapeutic strategies targeting the hurdles to axonal regeneration posed by these processes without compromising neuroprotection.
Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential
Authors: She Ruining , Liu Danhong , Liao Jun , Wang Guozuo , Ge Jinwen , Mei Zhigang
Published: May 2023

Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents the leading cause of mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade of pathophysiological events following the restoration of blood flow and reoxygenation, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, further aggravate the damage of brain tissue. Paradoxically, there are still no effective methods to prevent CI/RI, since the detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, which are characterized by mitochondrial oxidative stress, Ca2+ overload, iron dyshomeostasis, mitochondrial DNA (mtDNA) defects and mitochondrial quality control (MQC) disruption, are closely relevant to the pathological process of CI/RI. There is increasing evidence that mitochondrial dysfunctions play vital roles in the regulation of programmed cell deaths (PCDs) such as ferroptosis and PANoptosis, a newly proposed conception of cell deaths characterized by a unique form of innate immune inflammatory cell death that regulated by multifaceted PANoptosome complexes. In the present review, we highlight the mechanisms underlying mitochondrial dysfunctions and how this key event contributes to inflammatory response as well as cell death modes during CI/RI. Neuroprotective agents targeting mitochondrial dysfunctions may serve as a promising treatment strategy to alleviate serious secondary brain injuries. A comprehensive insight into mitochondrial dysfunctions-mediated PCDs can help provide more effective strategies to guide therapies of CI/RI in IS.
Case report: Treatment of advanced CSF1-receptor associated leukoencephalopathy with hematopoietic stem cell transplant
Authors: Bergner Caroline G. , Schäfer Lisa , Vucinic Vladan , Schetschorke Birthe , Lier Julia , Scherlach Cordula , Rullmann Michael , Sabri Osama , Classen Joseph , Platzbecker Uwe , Kühl Jörn-Sven , Barthel Henryk , Köhler Wolfgang , Franke Georg-Nikolaus
Published: May 2023

CSF1 receptor-related leukoencephalopathy is a rare genetic disorder presenting with severe, adult-onset white matter dementia as one of the leading symptoms. Within the central nervous system, the affected CSF1-receptor is expressed exclusively in microglia cells. Growing evidence implicates that replacing the defective microglia with healthy donor cells through hematopoietic stem cell transplant might halt disease progression. Early initiation of that treatment is crucial to limit persistent disability. However, which patients are suitable for this treatment is not clear, and imaging biomarkers that specifically depict lasting structural damage are lacking. In this study, we report on two patients with CSF1R-related leukoencephalopathy in whom allogenic hematopoietic stem cell transplant at advanced disease stages led to clinical stabilization. We compare their disease course with that of two patients admitted in the same timeframe to our hospital, considered too late for treatment, and place our cases in context with the respective literature. We propose that the rate of clinical progression might be a suitable stratification measure for treatment amenability in patients. Furthermore, for the first time we evaluate [18F] florbetaben, a PET tracer known to bind to intact myelin, as a novel MRI-adjunct tool to image white matter damage in CSF1R-related leukoencephalopathy. In conclusion, our data add evidence for allogenic hematopoietic stem cell transplant as a promising treatment in CSF1R-related leukoencephalopathy patients with slow to moderate disease progression.
Programmable RNA editing with endogenous ADAR enzymes – a feasible option for the treatment of inherited retinal disease?
Authors: Bellingrath Julia-Sophia , McClements Michelle E. , Fischer M. Dominik , MacLaren Robert E.
Published: May 2023

RNA editing holds great promise for the therapeutic correction of pathogenic, single nucleotide variants (SNV) in the human transcriptome since it does not risk creating permanent off-targets edits in the genome and has the potential for innovative delivery options. Adenine deaminases acting on RNA (ADAR) enzymes catalyse the most widespread form of posttranscriptional RNA editing in humans and their ability to hydrolytically deaminate adenosine to inosine in double stranded RNA (dsRNA) has been harnessed to change pathogenic single nucleotide variants (SNVs) in the human genome on a transcriptional level. Until now, the most promising target editing rates have been achieved by exogenous delivery of the catalytically active ADAR deaminase domain (ADARDD) fused to an RNA binding protein. While it has been shown that endogenous ADARs can be recruited to a defined target site with the sole help of an ADAR-recruiting guide RNA, thus freeing up packaging space, decreasing the chance of an immune response against a foreign protein, and decreasing transcriptome-wide off-target effects, this approach has been limited by a low editing efficiency. Through the recent development of novel circular ADAR-recruiting guide RNAs as well as the optimisation of ADAR-recruiting antisense oligonucleotides, RNA editing with endogenous ADAR is now showing promising target editing efficiency in vitro and in vivo. A target editing efficiency comparable to RNA editing with exogenous ADAR was shown both in wild-type and disease mouse models as well as in wild-type non-human primates (NHP) immediately following and up to 6 weeks after application. With these encouraging results, RNA editing with endogenous ADAR has the potential to present an attractive option for the treatment of inherited retinal diseases (IRDs), a field where gene replacement therapy has been established as safe and efficacious, but where an unmet need still exists for genes that exceed the packaging capacity of an adeno associated virus (AAV) or are expressed in more than one retinal isoform. This review aims to give an overview of the recent developments in the field of RNA editing with endogenous ADAR and assess its applicability for the field of treatment of IRD.
Comparative analysis of transcriptional changes in zebrafish cep290 and bbs2 mutants by RNA-seq reveals upregulation of inflammatory and stress-related pathways
Authors: Grabinski Sarah E. , Parsana Dhwani , Perkins Brian D.
Published: May 2023

Acute injury to the adult zebrafish retina triggers the release of pro-inflammatory cytokines and growth factors that stimulate multiple gene regulatory networks, which ultimately stimulate Müller glia to proliferate and regenerate neurons. In contrast, zebrafish carrying mutations in cep290 or bbs2 undergo progressive loss of cone photoreceptors and exhibit signs of microglia activation and inflammation, but the mutants fail to stimulate a regeneration response. To identify transcriptional changes that occur in zebrafish mutants undergoing progressive photoreceptor degeneration, RNA-seq transcriptional profiling was performed on cep290−/− and bbs2−/− retinas. The PANTHER Classification System was used to identify biological processes and signaling pathways that were differentially expressed between mutants and wild-type siblings during degeneration. As expected, genes associated with phototransduction were downregulated in cep290 and bbs2 mutants compared to wild-type siblings. Although both cep290 and bbs2 mutants undergo proliferation of rod precursors in response to retinal degeneration, the process of negatively regulating proliferation is enriched for upregulated genes, and this negative regulation may restrict proliferation of Müller glia and inhibit regeneration. A total of 815 differentially expressed genes (DEGs) were shared by cep290 and bbs2 retinas. Genes in pathways associated with inflammation, apoptosis, stress response, and PDGF signaling were overrepresented. Identifying the genes and biological pathways that are common in zebrafish models of inherited retinal degeneration provides a foundation for future studies on the mechanisms that regulate cell death as well as processes that prohibit Müller cell reprogramming or proliferation in a model capable of retinal regeneration. The pathways will provide targets for future interventions that may promote successful regeneration of lost photoreceptors.
Valorization of polyphenolic compounds from food industry by-products for application in polysaccharide-based nanoparticles
Authors: Rosales Thiécla Katiane Osvaldt , Fabi João Paulo
Published: May 2023

In the last decades, evidence has indicated the beneficial properties of dietary polyphenols. In vitro and in vivo studies support that the regular intake of these compounds may be a strategy to reduce the risks of some chronic non-communicable diseases. Despite their beneficial properties, they are poorly bioavailable compounds. Thus, the main objective of this review is to explore how nanotechnology improves human health while reducing environmental impacts with the sustainable use of vegetable residues, from extraction to the development of functional foods and supplements. This extensive literature review discusses different studies based on the application of nanotechnology to stabilize polyphenolic compounds and maintain their physical–chemical stability. Food industries commonly generate a significant amount of solid waste. Exploring the bioactive compounds of solid waste has been considered a sustainable strategy in line with emerging global sustainability needs. Nanotechnology can be an efficient tool to overcome the challenge of molecular instability, especially using polysaccharides such as pectin as assembling material. Complex polysaccharides are biomaterials that can be extracted from citrus and apple peels (from the juice industries) and constitute promising wall material stabilizing chemically sensitive compounds. Pectin is an excellent biomaterial to form nanostructures, as it has low toxicity, is biocompatible, and is resistant to human enzymes. The potential extraction of polyphenols and polysaccharides from residues and their inclusion in food supplements may be a possible application to reduce environmental impacts and constitutes an approach for effectively including bioactive compounds in the human diet. Extracting polyphenolics from industrial waste and using nanotechnology may be feasible to add value to food by-products, reduce impacts on nature and preserve the properties of these compounds.
Exploring the practice of nutritional support during hospitalization across physicians, dietitians, and pharmacists based in Saudi Arabia
Authors: Ajabnoor Sarah M. , Zaher Sara , Malatani Rania , Jawa Hani
Published: May 2023

Background

Nutritional support has a pivotal role in preventing and treating malnutrition. Recognizing the gaps in nutritional support practice can aid the development of tailored nutritional protocols. Therefore, this study aimed to assess the current practices, attitudes, and perceptions related to nutritional support for hospitalized patients in one of the largest Middle Eastern countries.

Methods

A cross-sectional study was conducted among different healthcare professionals currently working in hospitals in Saudi Arabia and involved in nutritional support practice. Data were collected using convenient sample via a self-administered web-based questionnaire.

Results

A total of 114 participants were included in this study. The majority were dietitians (54%), followed by physicians (33%) and pharmacists (12%), and were from the western region (71.9%). Various attitudes in many practices were observed among the participants. Only 44.7% of the participants had a formal nutritional support team. The mean confidence level of all respondents was significantly higher for enteral nutrition practice (7.7 ± 2.3) than for parenteral nutrition practice (6.1 ± 2.5) (p< 0.01). The confidence level for enteral nutrition practice was significantly influenced by nutritional qualification (β = 0.202,p< 0.05), type of healthcare facility (β = 0.210, p < 0.05), profession (β = -0.308,p< 0.01), and years of experience (β = 0.220,p< 0.05).

Conclusion

This study comprehensively assessed various aspects of nutritional support practice in Saudi Arabia. Healthcare practice of nutritional support should be guided by evidence-based guidelines. Professional qualification and training in nutritional support are essential for promoting practice in hospitals.
Diet quality and associated factors in Brazilian undergraduates during the COVID-19 pandemic
Authors: Galvão Liana L. P. , Santos Thanise S. S. , Slater Betzabeth , Lyra Clélia de O. , Rolim Priscilla M. , Ramalho Alanderson A. , Dalamaria Tatiane , Martins Fernanda Andrade , Höfelmann Doroteia A. , Crispim Sandra P. , Gorgulho Bartira M. , Rodrigues Paulo R. M. , Marchioni Dirce M. , Maciel Bruna L. L.
Published: May 2023

Background

Diet quality is associated with psychobiological, psychological, biological, and physiological factors of individuals, and in the context of prolonged stress, such as the COVID-19 pandemic, it can lead to a worsening of the quality of food for undergraduates. This study aimed to analyze diet quality and associated factors in Brazilian undergraduates.

Methods

Data were collected from 4,799 undergraduate students from all Brazilian regions, from August 2020 to February 2021. The online questionnaire contained socioeconomic variables, the ESQUADA scale to assess diet quality, self-referred changes in weight, the Brazilian food insecurity scale (EBIA), sleep assessment and the perceived stress scale. Unconditional multiple logistic regression analysis was performed to study variables associated with poor and very poor diet quality.

Results

Most of participants presented a good diet quality (51.7%), while 9.8% had a poor or very poor diet quality and only 1.1% had an excellent diet quality. 58.2% of undergraduates reported to have an increase in weight during the pandemic and 74.3% of the students presented elevated stress during the pandemic. Logistic regressions showed students who gained weight during the pandemic presented the highest AOR = 1.56 (95% CI = 1.12–2.20) for poor or very poor diet quality. The elevated perceived stress was also associated with a higher AOR = 2.85 (95% CI = 1.71–4.74) for poor or very poor diet quality.

Conclusion

Most of the studied undergraduates presented a good diet quality. Nevertheless, poor/very poor diet quality was associated with higher perceived stress and weight gain. Our study indicated that policies should beaimed at the socioeconomically most vulnerable undergraduates, those in a situation of food and nutritional insecurity, high perceived stress, and who gained weight during the pandemic.
Elevation of preoperative serum hs-CRP is an independent risk factor for malnutrition in patients with gastric cancer
Authors: Mao Yuantian , Liu Jinlu , Li Jiaming , Qiu Yue , Wang Zhen , Li Bopei , Liu Siyu , Tian Lei , Chen Junqiang
Published: May 2023

Background

Recent studies have reported hypersensitive C-reactive protein (hs-CRP) linked to clinicopathological characteristics and nutritional status of the tumor, but its clinical significance in GC remains unclear. This study aimed to investigate the relationship between preoperative serum hs-CRP level and clinicopathological features and nutritional status in gastric cancer (GC) patients.

Methods

The clinical data of 628 GC patients who met the study criteria were analyzed retrospectively. The preoperative serum hs-CRP level was divided into two groups (<1 mg/L and ≥1 mg/L) to evaluate clinical indicators. Nutritional Risk Screening and nutritional assessment of GC patients were performed by the Nutritional Risk Screening 2002 (NRS2002) and the Patient-Generated Subjective Global Assessment (PG-SGA), respectively. The data were subjected to chi-square test, univariate and multivariate logistic regression analyses, respectively.

Results

The analysis of 628 GC cases revealed that 338 patients (53.8%) were on malnutrition risk(NRS2002≥3 points), and 526(83.8%) had suspected/moderate to severe malnutrition(PG-SGA≥ 2 points). Preoperative serum hs-CRP level was significantly correlated with age, tumor maximum diameter (TMD), peripheral nerve invasion (PNI), lymph-vascular invasion (LVI), depth of tumor invasion (DTI), lymph node metastasis (LNM), pTNM stage, body weight loss (BWL), body mass index (BMI), NRS2002 score, PG-SGA grade, hemoglobin (HB), total protein (TP), albumin (ALB), prealbumin (PAB) and total lymphocyte count (TLC). Multivariate logistic regression analysis revealed that hs-CRP (OR=1.814, 95%CI=1.174-2.803; P=0.007), age, ALB, BMI, BWL and TMD were independent risk factors for existing malnutritional risk in GC. Similarly, non-malnutrition and suspected/moderate to severe malnutrition groups presented that hs-CRP (OR=3.346, 95%CI=1.833-6.122; P< 0.001), age, HB, ALB, BMI and BWL were independent risk factors for malnutrition in GC.

Conclusion

In addition to the generally used nutritional evaluation indicators such as age, ALB, BMI, and BWL, the hs-CRP level may be used as a nutritional screening and evaluation indicator for GC patients.
Analysis of bronchovascular patterns in the left superior division segment to explore the relationship between the descending bronchus and the artery crossing intersegmental planes
Authors: Li Zhikai , Zhao Qingtao , Wu Wenbo , Hu Zhonghui , Zhang Xiaopeng
Published: May 2023

Background

A comprehensive understanding of the anatomical variations in the pulmonary bronchi and arteries is particularly essential to the implementation of safe and precise left superior division segment (LSDS) segmentectomy. However, no report shows the relationship between the descending bronchus and the artery crossing intersegmental planes. Thus, the purpose of the present study was to analyze the branching pattern of the pulmonary artery and bronchus in LSDS using three-dimensional computed tomography bronchography and angiography (3D-CTBA) and to explore the associated pulmonary anatomical features of the artery crossing intersegmental planes.

Materials and methods

The 3D-CTBA images of 540 cases were retrospectively analyzed. We reviewed the anatomical variations of the LSDS bronchus and artery and assorted them according to different classifications.

Results

Among all 540 cases of 3D-CTBA, there were 16 cases (44.4%) with lateral subsegmental artery crossing intersegmental planes (AX3a), 20 cases (55.6%) Without AX3a in the descending B3a or B3 type, and 53 cases (10.5%) with AX3a, 451 cases (89.5%) Without AX3a in the Without the descending B3a or B3 type. This illustrated that the AX3a was more common in the descending B3a or B3 type (P < 0.005). Similarly, there were 69 cases (36.1%) with horizontal subsegmental artery crossing intersegmental planes (AX1 + 2c), 122 cases (63.9%) Without AX1 + 2c in the descending B1 + 2c type, and 33 cases (9.5%) with AX1 + 2c, 316 cases (90.5%) Without AX1 + 2c in the Without the descending B1 + 2c type. Combinations of the branching patterns of the AX1 + 2c and the descending B1 + 2c type were significantly dependent (p < 0.005). The combinations of the branching patterns of the AX1 + 2c and the descending B1 + 2c type were frequently observed.

Conclusions

This is the first report to explore the relationship between the descending bronchus and the artery crossing intersegmental planes. In patients with the descending B3a or B3 type, the incidence of the AX3a was increased. Similarly, the incidence of the AX1 + 2c was increased in patients with the descending B1 + 2c type. These findings should be carefully identified when performing an accurate LSDS segmentectomy.
Tackling the dysregulated immune-checkpoints in classical Hodgkin lymphoma: bidirectional regulations between the microenvironment and Hodgkin/Reed-Sternberg cells
Authors: Cellini Alessandro , Scarmozzino Federico , Angotzi Francesco , Ruggeri Edoardo , Dei Tos Angelo Paolo , Trentin Livio , Pizzi Marco , Visentin Andrea
Published: May 2023

Immune evasion is considered one of the modern hallmarks of cancer and is a key element in the pathogenesis of classical Hodgkin Lymphoma (cHL). This haematological cancer achieves effective avoidance of the host’s immune system by overexpressing the PD-L1 and PD-L2 proteins on the surface of the neoplastic cells. Subversion of the PD-1/PD-L axis, however, is not the sole contributor to immune evasion in cHL, as the microenvironment nurtured by the Hodgkin/Reed-Sternberg cells is a major player in the creation of a biological niche that sustains their survival and hinders immune recognition. In this review, we will discuss the physiology of the PD-1/PD-L axis and how cHL is able to exploit a plethora of different molecular mechanisms to build an immunosuppressive microenvironment and achieve optimal immune evasion. We will then discuss the success obtained by checkpoint inhibitors (CPI) in treating cHL, both as single agents and as part of combination strategies, analysing the rationale for their combination with traditional chemotherapeutic compounds and the proposed mechanisms of resistance to CPI immunotherapy.
Medical cannabinoids for painful symptoms in patients with severe dementia: a randomized, double-blind cross-over placebo-controlled trial protocol
Authors: Bianchi Federica , Pautex Sophie , Wampfler James , Curtin François , Daali Youssef , Desmeules Jules Alexandre , Broers Barbara
Published: May 2023

Background

In an observational study in Geneva (Switzerland), we found that administering a standardized THC/CBD oil was feasible, safe, and beneficial in an elderly polymedicated population with severe dementia, behavioral troubles, and pain. Those findings need to be confirmed in a randomized clinical trial.

Objectives

The MedCanDem trial is a randomized, double-blind cross-over placebo-controlled trial to study the efficacy of cannabinoids in improving painful symptoms during severe dementia disorders in patients living in long-term care facilities in Geneva. This manuscript describes the MedCanDem trial protocol.

Materials and methods

Participants will be patients suffering from severe dementia associated with pain and behavioral troubles and living in long-term care facilities. We selected five facilities specialized in caring for severely demented patients in Geneva (Switzerland). A total of 24 subjects will be randomized 1:1 to the sequence study intervention/placebo or the sequence placebo/study intervention. Patients will receive study intervention treatment or placebo for eight weeks, and then after a one-week wash-out, treatments will be inversed for another eight weeks. The intervention will be a standardized THC/CBD 1:2 oil extract, and the placebo will be a hemp seed oil. The primary outcome is the reduction from the baseline of the Cohen-Mansfield score; secondary outcomes include the reduction in the Doloplus scale, the reduction of rigidity, the monitoring of concomitant drugs prescription and de-prescription, the safety assessment, and a pharmacokinetic evaluation. The primary and secondary outcomes will be assessed at the baseline, after 28 days, and at the end of both study periods. In addition, safety laboratory analysis, pharmacokinetic evaluation, and therapeutic drug monitoring for the cannabinoids will be evaluated through a blood sample analysis conducted at the beginning and the end of both study periods.

Discussion and conclusion

This study will allow us to confirm the clinical results observed during the observational study. It represents one of the few studies aiming to prove natural medical cannabis efficacy in a population of non-communicating patients with severe dementia, experimenting with behavioral troubles, pain, and rigidity.

Trial registration

The trial has Swissethics authorization (BASEC 2022-00999), and it is registered on clinicaltrials.gov (NCT05432206) and the SNCTP (000005168).
Principles of care for pregnant and parenting people with substance use disorder: the obstetrician gynecologist perspective
Authors: Barber Cecily May , Terplan Mishka
Published: May 2023

Substance use in pregnant and parenting persons is common, yet still underdiagnosed. Substance use disorder (SUD) is one of the most stigmatized and undertreated chronic medical conditions, and this is exacerbated in the perinatal period. Many providers are not sufficiently trained in screening or treatment for substance use, so gaps in care for this population persist. Punitive policies towards substance use in pregnancy have proliferated, lead to decreased prenatal care, do not improve birth outcomes, and disproportionately impact Black, Indigenous, and other families of color. We discuss the importance of understanding the unique barriers of pregnancy-capable persons and drug overdose as one of the leading causes of maternal death in the United States. We highlight the principles of care from the obstetrician-gynecologist perspective including care for the dyad, person-centered language, and current medical terminology. We then review treatment of the most common substances, discuss SUD during the birthing hospitalization, and highlight the high risk of mortality in the postpartum period.
Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis
Authors: Chen Dinghua , Niu Yue , Liu Fei , Yang Yue , Wang Xue , Li Ping , Chen Xiangmei
Published: May 2023

Aim: We performed a systematic review and network meta-analysis evaluating the safety and efficacy of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) among dialysis chronic kidney disease patients.

Methods: Safety was evaluated with any adverse events (AEs), serious adverse events (SAEs), and 12 common events. Efficacy was mainly analyzed with hemoglobin response. All reported results were summarized using mean difference and risk ratio (RR) with 95% confidence interval (CI). Publication bias was assessed through funnel plots.

Results: Twenty trials (19 studies) with 14,947 participants were included, comparing six HIF-PHIs with erythropoiesis-stimulating agents (ESAs). No significant differences were indicated in overall AEs and SAEs between each HIF-PHI and ESA. The occurrence of gastrointestinal disorder was higher in enarodustat and roxadustat than in ESAs (RR: 6.92, 95% CI: 1.52–31.40, p = 0.01; RR: 1.30, 95% CI: 1.04–1.61, p = 0.02). The occurrence of hypertension was lower in vadadustat than in ESAs (RR: 0.81, 95% CI: 0.69–0.96, p = 0.01). The occurrence of vascular-access complications was higher in roxadustat (RR: 1.15, 95% CI: 1.04–1.27, p<0.01) and lower in daprodustat (RR: 0.78, 95% CI: 0.66–0.92, p<0.01) than in ESAs. In the risk of the other nine events, including cardiovascular events, no significant differences were observed between HIF-PHIs and ESAs. For hemoglobin response, network meta-analysis showed that compared with ESAs, significant increases were shown in roxadustat (RR: 1.04, 95% CI: 1.01–1.07, p<0.01) and desidustat (RR: 1.22, 95% CI: 1.01–1.48, p = 0.04), whereas noticeable reductions were indicated in vadadustat (RR: 0.88, 95% CI: 0.82–0.94, p<0.01) and molidustat (RR: 0.83, 95% CI: 0.70–0.98, p = 0.02). There was no significant difference between daprodustat and ESAs (RR: 0.97, 95% CI: 0.89–1.06, p = 0.47).

Conclusion: Although HIF-PHIs did not show significant differences from ESAs in terms of overall AEs and SAEs, statistical differences in gastrointestinal disorder, hypertension, and vascular-access complications were observed between HIF-PHIs, which deserved to be noted in clinical decision making.

Systematic review registration: This study is registered with PROSPERO (registration number CRD42022312252)
A randomized controlled trial to evaluate the impact of pharmacist-led clinical interventions on the health-related quality of life among TB patients
Authors: Khan Farman Ullah , Khan Faiz Ullah , Aqeel Muhammad Tahir , Hayat Khezar , Chang Jie , Rehman Asim ur , Fang Yu
Published: May 2023

Background: The study was designed to evaluate the impact of pharmacist-led clinical interventions on the health-related quality of life among tuberculosis patients in Pakistan.

Methods: A randomized, controlled prospective study was carried out in a Pakistan Institute of Medical Sciences hospital tuberculosis (TB) control center. Participants who visited the TB center between September 2020 and December 2021 were randomly assigned to two clusters, the usual care group (UC group) vs. the intervention group (pharmaceutical care group), in a 1:1 ratio by a simple envelope technique. In the intervention group, a patient received centered care that encompassed informed decision-making, which can increase the quality of care and monitoring of adverse drug events. However, the control group received routine TB treatment at the hospital. The EuroQol-5D-3L instrument was used to assess the health-related quality of life (HRQoL) at the baseline and in the third and sixth months of the treatment time period.

Results: A total of 503 patients were eligible, of which only 426 patients were included in this study. At the end of the study, n = 205 of the patients in the intervention group and n = 185 of those in the control group were analyzed. In the intervention group, the EQ-5D-3L health utility score improved significantly (p < 0.001) (from the baseline mean ± SD, 0.40 ± 0.36, to 6 months of treatment, 0.89 ± 0.09, while in the control group from 0.42 ± 0.35 to 0.78 ± 0.27). In multivariate regression analysis, the variables that remained statistically associated (p < 0.001) with the HRQoL (unstandardized β [95% confidence interval]) of the control group were as follows: gender, female vs. male (-0.039 [-0.076 to -0.003]); body weight, less than 40 kg vs. more than 40 kg (-0.109 [-0.195 to -0.024]); patients with any comorbidity vs. without comorbidity (-0.136 [-0.252 to -0.020]); and smokers vs. non-smokers (-0.204 [-0.291 to -0.118]). The study did not find any statistically significant associations between the intervention group’s variables and the HRQoL.

Conclusion: Patient-centered care interventions led by pharmacists as part of care coordination enhanced the HRQoL for TB patients significantly. According to this study, clinical pharmacists should be included in the interdisciplinary clinical staff for TB patient management.
Case report: Fatal poisoning caused by additive effects of two barbiturates
Authors: Takei Sella , Kinoshita Hiroshi , Jamal Mostofa , Kumihashi Mitsuru , Yamashita Tadayoshi , Tanaka Etsuko , Kawahara Sachiko , Abe Hiroko , Tsutsui Kunihiko , Kimura Shoji
Published: May 2023

A case of fatal poisoning involving multiple psychotropic drugs is presented. Quantitative toxicological analysis showed femoral blood concentrations of pentobarbital, phenobarbital, duloxetine, acetaminophen and tramadol were 10.39, 22.57, 0.22, 0.61 and 0.22 μg/ml, respectively. We concluded that the death was due to the additive effects of two barbiturates. As both pentobarbital and phenobarbital act on gamma-aminobutyric acid (GABA) receptors, central nervous system activity was suppressed, causing respiratory depression. Additive pharmacological effects should be considered in cases of massive ingestion of multiple drugs.
Carrier-envelope offset frequency measurement by means of an external optical resonator
Authors: Giannotti Dario , Suerra Edoardo , Canella Francesco , Cialdi Simone , Laporta Paolo , Galzerano Gianluca
Published: May 2023

A general-purpose method based on the implementation of the asymmetric Pound–Drever–Hall (PDH) technique is proposed to measure the carrier-envelope offset (CEO) frequency of a mode-locked laser using an external optical cavity. By analyzing the synchronously demodulated signal of the spectrally filtered cavity reflection when the optical resonator is locked to the mode-locked laser, a discriminating signal depending on the relative frequency offset between the mode-locked and optical cavity comb-like spectra is obtained. For a given geometry and group delay dispersion (GDD) of the cavity parameters (i.e., a known cavity mode offset), this signal can be used to retrieve the laser CEO. This approach turns out to be advantageous in terms of setup complexity with respect to other well-known techniques that rely on non-linear frequency generation, such as f–2f interferometers. In addition, this method can be used to precisely determine the laser–cavity spectral coupling, which is an important topic in cavity-enhanced spectroscopy and non-linear optics applications. After the theoretical description of the generalized asymmetric PDH signal, an experimental validation of the proposed method is reported using an Er-doped fiber frequency comb source centered at 1,550 nm, with a repetition rate of 250 MHz, locked to a linear optical cavity with a 1 GHz free spectral range. The theoretical effect of the GDD is confirmed experimentally using different cavity configurations. Moreover, the comparison with the CEO frequency values measured using an f–2f interferometer demonstrates the feasibility of the proposed method.
Blaming it on NATO? Framing the role of NATO in the full-scale Russian invasion of Ukraine on Twitter
Authors: Kobilke Lara , Kulichkina Aytalina , Baghumyan Ani , Pipal Christian
Published: May 2023

Introduction

Since social media has become a significant tool for conflict communication amid the full-scale Russian invasion of Ukraine, researchers have grown more interested in the digital content citizens are exposed to.

Methods

To further investigate the role of social media in the ongoing invasion, we conducted a manual content analysis to examine tweets in English, Russian, and German that explicitly mentioned NATO in the context of the full-scale invasion during February to May 2022. Our analysis explored how these language-specific Twitter communities framed NATO's role in the conflict.

Results

We found that English-speaking tweeters were more likely to hold NATO responsible for finding a solution and least likely to blame NATO for the war compared to German and Russian speakers. We also observed that the Russian-speaking Twitter community exhibits a comparatively lower tendency to hold NATO accountable for the ongoing war as compared to their German-speaking counterparts, and they are also notably the least likely to expect NATO to bring an end to the war. Finally, English-speaking Twitter users who attribute blame to NATO for the ongoing war tend to adhere to a preconceived notion, rather than arriving at an interpretation based on the situation at hand. This is in contrast to the Russian-speaking community, where the opposite is true. German-speaking users fall somewhere in between these two perspectives.

Discussion

Our research contributes to the literature by providing a novel integration of conceptual and methodological perspectives on the framing and stance-taking of social media users during wartime, addressing known research gaps in the comparative analysis of these discussions, i.e., adding “non-English” perspectives. It also highlights the importance of cultural and linguistic sensitivity when addressing responsibility in armed conflicts and the need to consider the diverse perspectives derived from divergent problem definitions and evaluative standards.
The emergence of phonological dispersion through interaction: an exploratory secondary analysis of a communicative game
Authors: Roberts Gareth , Clark Robin
Published: May 2023

Introduction

Why is it that phonologies exhibit greater dispersion than we might expect by chance? In earlier work we investigated this using a non-linguistic communication game in which pairs of participants sent each other series of colors to communicate a set of animal silhouettes. They found that above-chance levels of dispersion, similar to that seen in vowel systems, emerged as a result of the production and perception demands acting on the participants. However, they did not investigate the process by which this dispersion came about.

Method

To investigate this we conducted a secondary statistical analysis of the data, looking in particular at how participants approached the communication task, how dispersion emerged, and what convergence looked like.

Results

We found that dispersion was not planned from the start but emerged as a large-scale consequence of smaller-scale choices and adjustments. In particular, participants learned to reproduce colors more reliably over time, paid attention to signaling success, and shifted towards more extreme areas of the space over time.

Conclusion

This study sheds light on the role of interactive processes in mediating between human minds and the emergence or larger-scale structure, as well as the distribution of features across the world's languages.
Mixed-mode Zentangle and Pastel Nagomi artwork for improving mental well-being in university students during COVID-19 pandemic – a randomized controlled feasibility trial
Authors: Cheung Kin , Ma Ka Yan , Tsang Hilda , Leung Nok Hang , Lui Ka Yee , Ho Sze Wing
Published: May 2023

Background

University students are identified as a high-risk group for mental health problems. Artworks have been found effective in enhancing individuals’ mental well-being in different populations, but none have been conducted on university students. This study was to address this research gap to determine the feasibility and estimate the preliminary effects of Zentangle and Pastel Nagomi on the mental well-being of undergraduate students during the COVID-19 pandemic.

Method

This was a 3-arm randomized controlled trial, with 33 undergraduates allocated to two 8-week artworks (Zentangle or Pastel Nagomi Art group) and a control group. Data were collected at baseline, and weeks 4, 6, 8, and 12. Focus group interviews were conducted at the 12-week follow-up.

Results

The consent and attrition rates were 80.5 and 6.06%, respectively. The attendance rate ranged from 83.3 to 100%. Compared with the control group, the Pastel Nagomi art group had a significant improvement in retaining positive affect at week 6. This retention could be further observed at week 12. Moreover, the Zentangle group had a significant increase in positive affect at week 4, with better retention at week 12. In addition, the within-group analyses showed that the Pastel Nagomi art group had significantly decreased negative affect at weeks 6 and week 12; and the Zentangle group had significantly decreased depression at week 8. The qualitative findings suggested that the intervention resulted in the participants enjoying the artwork process, and being proud of their artwork and personal growth.

Limitation

The study included an imbalance number of online vs. face-to-face sessions, and repeated measures may have affected the results.

Conclusion

The study suggests that both artworks are effective in improving undergraduates’ mental well-being and that it is feasible to conduct future large-scale studies (263 words).