bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Cancer Stem Cells a Suitable Target for Breast Cancer Immunotherapy?
Authors: Ruiu Roberto , Di Lorenzo Antonino , Cavallo Federica , Conti Laura
Published: April 2022

There is substantial evidence to suggest that complete tumor eradication relies on the effective elimination of cancer stem cells (CSCs). CSCs have been widely described as mediators of resistance to conventional therapies, including chemo- and radiotherapy, as well as of tumor metastasization and relapse in different tumor types, including breast cancer. However, the resistant phenotype of CSCs makes their targeting a tough task, and immunotherapy may therefore be an interesting option. Nevertheless, although immunotherapeutic approaches to cancer treatment have generated great enthusiasm due to recent success in clinics, breast cancer treatment mostly relies on standard approaches. In this context, we review the existing literature on the immunological properties of breast CSC and immunotherapeutic approaches to them. We will thus attempt to clarify whether there is room for the immunotargeting of breast CSCs in the current landscape of breast cancer therapies. Finally, we will provide our opinion on the CSC-targeting immunotherapeutic strategies that could prospectively be attempted.
Circular RNA ERBIN Promotes Proliferation of Hepatocellular Carcinoma via the miR-1263/CDK6 Axis
Authors: Yang Shikun , Yu Fei , Ji Yang , Shen Yanjun , Lu Hao , Gao Yuan , Zhang Feng , Wang Xuehao , Zhang Chuanyong
Published: April 2022

Objectives

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and characterized by high aggressiveness and extremely poor prognosis. Increasing evidence has suggested that circular RNAs (circRNAs), which are highly stable, play crucial roles in the progression of multiple malignancies. However, the roles of circRNAs in HCC remain elusive.

Materials and Methods

The expression patterns of circRNAs in HCC were identified by qRT-PCR. A series of functional experiments both in vivo and in vitro were used to determine the role of circERBIN in HCC proliferation. Bioinformatics and an RNA pulldown assay were used to identify potential downstream targets of circERBIN.

Results

The expression of circERBIN was upregulated in HCC cell lines and tissues, which was predictive of a poor prognosis in HCC patients. Elevated circERBIN promoted G1/S transition of HCC cells, thus facilitating the proliferation and tumorigenesis of HCC cells. Mechanistic investigations revealed that circERBIN regulated HCC proliferation by acting as a sponge of miR-1263, which subsequently targeted cyclin dependent kinase 6 and controlled G1/S transition.

Conclusion

Taken together, these results determined that circERBIN functions as an important epigenetic regulator in HCC development, highlighting that circERBIN is a promising target for treatment of HCC.
Functional Interaction Between the Oncogenic Kinase NEK2 and Sam68 Promotes a Splicing Program Involved in Migration and Invasion in Triple-Negative Breast Cancer
Authors: Naro Chiara , Barbagallo Federica , Caggiano Cinzia , De Musso Monica , Panzeri Valentina , Di Agostino Silvia , Paronetto Maria Paola , Sette Claudio
Published: April 2022

Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype. Poor prognosis in TNBC is partly due to lack of efficacious targeted therapy and high propensity to metastasize. Dysregulation of alternative splicing has recently emerged as a trait of TNBC, suggesting that unveiling the molecular mechanisms underlying its regulation could uncover new druggable cancer vulnerabilities. The oncogenic kinase NEK2 is significantly upregulated in TNBC and contributes to shaping their unique splicing profile. Herein, we found that NEK2 interacts with the RNA binding protein Sam68 in TNBC cells and that NEK2-mediated phosphorylation of Sam68 enhances its splicing activity. Genome-wide transcriptome analyses identified the splicing targets of Sam68 in TNBC cells and revealed a common set of exons that are co-regulated by NEK2. Functional annotation of splicing-regulated genes highlighted cell migration and spreading as biological processes regulated by Sam68. Accordingly, Sam68 depletion reduces TNBC cell migration and invasion, and these effects are potentiated by the concomitant inhibition of NEK2 activity. Our findings indicate that Sam68 and NEK2 functionally cooperate in the regulation of a splicing program that sustains the pro-metastatic features of TNBC cells.
The Biological Functions and Clinical Values of Exosomal Circular RNAs in Hepatocellular Carcinoma
Authors: Zhao Ying , Yao Jinmei
Published: April 2022

Hepatocellular carcinoma (HCC) exacts a heavy disease burden and is currently the second most common cause of cancer-related deaths worldwide. HCC usually lacks obvious symptoms in the early stage, and most HCC patients are diagnosed at advanced stages with poor prognosis. Circular RNAs (circRNAs) are single-stranded RNAs that form covalently closed loops and are stable in exosomes. Exosomes are known as important messengers of the cross-talk between tumor and immune cells. Accumulating studies have demonstrated the promoter or suppressor roles of exosomal circRNAs in the carcinogenesis, progression, and metastasis of HCC. In this review, we summarized the current studies on the biological functions and diagnostic and prognostic values of exosomal circRNAs in HCC progression.
Short-Term Effects of Elexacaftor/Tezacaftor/Ivacaftor Combination on Glucose Tolerance in Young People With Cystic Fibrosis—An Observational Pilot Study
Authors: Korten Insa , Kieninger Elisabeth , Krueger Linn , Bullo Marina , Flück Christa E. , Latzin Philipp , Casaulta Carmen , Boettcher Claudia
Published: April 2022

Background

The effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on glucose tolerance and/or cystic-fibrosis-related diabetes (CFRD) is not well understood. We performed an observational study on the short-term effects of ELX/TEZ/IVA on glucose tolerance.

Methods

Sixteen adolescents with CF performed oral glucose tolerance tests (OGTT) before and 4–6 weeks after initiating ELX/TEZ/IVA therapy. A continuous glucose monitoring (CGM) system was used 3 days before until 7 days after starting ELX/TEZ/IVA treatment.

Results

OGTT categories improved after initiating ELX/TEZ/IVA therapy (p = 0.02). Glucose levels of OGTT improved at 60, 90, and 120 min (p < 0.05), whereas fasting glucose and CGM measures did not change.

Conclusion

Shortly after initiating ELX/TEZ/IVA therapy, glucose tolerance measured by OGTT improved in people with CF. This pilot study indicates that ELX/TEZ/IVA treatment has beneficial effects on the endocrine pancreatic function and might prevent or at least postpone future CFRD.
Long Term Follow up of Patients With Primary Obstetric Antiphospholipid Syndrome
Authors: Niznik Stanley , Rapoport Micha J. , Avnery Orly , Lubetsky Aharon , Shavit Ronen , Ellis Martin H. , Agmon-Levin Nancy
Published: April 2022

Introduction: Primary obstetric antiphospholipid syndrome (OAPS) is defined by specific morbidities and/or losses of pregnancy in the presence of persistent antiphospholipid antibodies (aPL). This variant of APS is usually treated during pregnancy and the post-partum period. Data on occurrence of thrombotic event during long term follow-up of OAPS patients is limited.

Methods: A multi-centre retrospectively cohort of female patients with primary APS (pAPS) was assembled during 2004–2019. Patients were grouped according to disease presentation as pure OAPS or thrombotic APS (tAPS) for those presenting with thrombosis. Clinical and serological data were compared between groups.

Results: Of 219 pAPS female patients 67 (30.6%) were diagnosed with OAPS and 152 (69.4%) with tAPS. During >10 years of follow-up 24/67 (35.8%) OAPS and 71/152 (50%) tAPS suffered a new thrombotic event (p = 0.06), while obstetric morbidity was more likely in the OAPS group (31.3 vs. 10.5%, p < 0.001) respectively. Among patients with OAPS at presentation heart valve disease and the presence of ANA were related to thrombosis following diagnosis (25 vs. 4.7%, p = 0.02; and 45.8 vs. 20.8%, p = 0.04 respectively).

Conclusion: Thrombotic event following diagnosis were common among female patients with pAPS regardless of disease presentation. Heart valve disease and ANA positivity may be risk factors for thrombosis during follow-up of patients presenting with pure OAPS.
New Insight in HDACs: Potential Therapeutic Targets for the Treatment of Atherosclerosis
Authors: Luan Yi , Liu Hui , Luan Ying , Yang Yang , Yang Jing , Ren Kai-Di
Published: April 2022

Atherosclerosis (AS) features include progressive hardening and reduced elasticity of arteries. AS is the leading cause of morbidity and mortality. An increasing amount of evidence showed that epigenetic modifications on genes serve are a main cause of several diseases, including AS. Histone deacetylases (HDACs) promote the deacetylation at lysine residues, thereby condensing the chromatin structures and further inhibiting the transcription of downstream genes. HDACs widely affect various physiological and pathological processes through transcriptional regulation or deacetylation of other non-histone proteins. In recent years, the role of HDACs in vascular systems has been revealed, and their effects on atherosclerosis have been widely reported. In this review, we discuss the members of HDACs in vascular systems, determine the diverse roles of HDACs in AS, and reveal the effects of HDAC inhibitors on AS progression. We provide new insights into the potential of HDAC inhibitors as drugs for AS treatment.
A Tau Pathogenesis-Based Network Pharmacology Approach for Exploring the Protections of Chuanxiong Rhizoma in Alzheimer’s Disease
Authors: Zeng Peng , Su Hong-Fei , Ye Chao-Yuan , Qiu Shuo-Wen , Shi Anbing , Wang Jian-Zhi , Zhou Xin-Wen , Tian Qing
Published: April 2022

Alzheimer’s disease (AD) is the most common cause of neurodegenerative dementia and one of the top medical concerns worldwide. Currently, the approved drugs to treat AD are effective only in treating the symptoms, but do not cure or prevent AD. Although the exact causes of AD are not understood, it is recognized that tau aggregation in neurons plays a key role. Chuanxiong Rhizoma (CR) has been widely reported as effective for brain diseases such as dementia. Thus, we explored the protections of CR in AD by a tau pathogenesis–based network pharmacology approach. According to ultra-HPLC with triple quadrupole mass spectrometry data and Lipinski’s rule of five, 18 bioactive phytochemicals of CR were screened out. They were shown corresponding to 127 tau pathogenesis–related targets, among which VEGFA, IL1B, CTNNB1, JUN, ESR1, STAT3, APP, BCL2L1, PTGS2, and PPARG were identified as the core ones. We further analyzed the specific actions of CR-active phytochemicals on tau pathogenesis from the aspects of tau aggregation and tau-mediated toxicities. It was shown that neocnidilide, ferulic acid, coniferyl ferulate, levistilide A, Z-ligustilide, butylidenephthalide, and caffeic acid can be effective in reversing tau hyperphosphorylation. Neocnidilide, senkyunolide A, butylphthalide, butylidenephthalide, Z-ligustilide, and L-tryptophan may be effective in promoting lysosome-associated degradation of tau, and levistilide A, neocnidilide, ferulic acid, L-tryptophan, senkyunolide A, Z-ligustilide, and butylidenephthalide may antagonize tau-mediated impairments of intracellular transport, axon and synaptic damages, and neuron death (especially apoptosis). The present study suggests that acting on tau aggregation and tau-mediated toxicities is part of the therapeutic mechanism of CR against AD.
Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury
Authors: Ismaiel Nada , Whynot Sara , Geldenhuys Laurette , Xu Zhaolin , Slutsky Arthur S. , Chappe Valerie , Henzler Dietrich
Published: April 2022

Background and Objective: Lung-protective mechanical ventilation is known to attenuate ventilator-associated lung injury (VALI), but often at the expense of hypoventilation and hypercapnia. It remains unclear whether the main mechanism by which VALI is attenuated is a product of limiting mechanical forces to the lung during ventilation, or a direct biological effect of hypercapnia.

Methods: Acute lung injury (ALI) was induced in 60 anesthetized rats by the instillation of 1.25 M HCl into the lungs via tracheostomy. Ten rats each were randomly assigned to one of six experimental groups and ventilated for 4 h with: 1) Conventional HighVENormocapnia (high VT, high minute ventilation, normocapnia), 2) Conventional Normocapnia (high VT, normocapnia), 3) Protective Normocapnia (VT 8 ml/kg, high RR), 4) Conventional iCO2Hypercapnia (high VT, low RR, inhaled CO2), 5) Protective iCO2Hypercapnia (VT 8 ml/kg, high RR, added CO2), 6) Protective endogenous Hypercapnia (VT 8 ml/kg, low RR). Blood gasses, broncho-alveolar lavage fluid (BALF), and tissue specimens were collected and analyzed for histologic and biologic lung injury assessment.

Results: Mild ALI was achieved in all groups characterized by a decreased mean PaO2/FiO2 ratio from 428 to 242 mmHg (p < 0.05), and an increased mean elastance from 2.46 to 4.32 cmH2O/L (p < 0.0001). There were no differences in gas exchange among groups. Wet-to-dry ratios and formation of hyaline membranes were significantly lower in low VT groups compared to conventional tidal volumes. Hypercapnia reduced diffuse alveolar damage and IL-6 levels in the BALF, which was also true when CO2 was added to conventional VT. In low VT groups, hypercapnia did not induce any further protective effect except increasing pulmonary IL-10 in the BALF. No differences in lung injury were observed when hypercapnia was induced by adding CO2 or decreasing minute ventilation, although permissive hypercapnia decreased the pH significantly and decreased liver histologic injury.

Conclusion: Our findings suggest that low tidal volume ventilation likely attenuates VALI by limiting mechanical damage to the lung, while hypercapnia attenuates VALI by limiting pro-inflammatory and biochemical mechanisms of injury. When combined, both lung-protective ventilation and hypercapnia have the potential to exert an synergistic effect for the prevention of VALI.
Differential Physiological, Transcriptomic, and Metabolomic Responses of Paspalum wettsteinii Under High-Temperature Stress
Authors: Zhao Xin , Huang Li-Juan , Sun Xiao-Fu , Zhao Li-Li , Wang Pu-Chang
Published: April 2022

Global warming has far-reaching effects on plant growth and development. As a warm-season forage grass, Paspalum wettsteinii is highly adaptable to high temperatures. However, the response mechanism of P. wettsteinii under high-temperature stress is still unclear. Therefore, we investigated the physiological indicators, transcriptome and metabolome of P. wettsteinii under different heat stress treatments. Plant height, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the contents of soluble sugar, proline, chlorophyll a, and chlorophyll b increased and then decreased, while the malondialdehyde (MDA) content decreased and then increased with increasing heat stress. Transcriptomic analysis revealed that genes related to energy and carbohydrate metabolism, heat shock proteins (HSPs), and transcription factors (TFs), secondary metabolite biosynthesis and the antioxidant system significantly changed to varying degrees. Metabolomic analysis showed that only free fatty acids were downregulated, while amino acids and their derivatives, organic acids, flavonoids, and sugars were both up- and downregulated under heat stress. These combined analyses revealed that growth was promoted at 25–40°C, while at 45°C, excess reactive oxygen species (ROS) damage reduced antioxidant and osmoregulatory effects and inactivated genes associated with the light and electron transport chains (ETCs), as well as damaged the PS II system and inhibited photosynthesis. A small number of genes and metabolites were upregulated to maintain the basic growth of P. wettsteinii. The physiological and biochemical changes in response to high-temperature stress were revealed, and the important metabolites and key genes involved in the response to high temperature were identified, providing an important reference for the physiological and molecular regulation of high-temperature stress in plants.
Neural Response to Low Energy and High Energy Foods in Bulimia Nervosa and Binge Eating Disorder: A Functional MRI Study
Authors: Donnelly Brooke , Foroughi Nasim , Williams Mark , Touyz Stephen , Madden Sloane , Kohn Michael , Clark Simon , Sachdev Perminder , Peduto Anthony , Caterson Ian , Russell Janice , Hay Phillipa
Published: April 2022

Objective

Bulimia nervosa (BN) and binge eating disorder (BED) are eating disorders (EDs) characterized by recurrent binge eating (BE) episodes. Overlap exists between ED diagnostic groups, with BE episodes presenting one clinical feature that occurs transdiagnostically. Neuroimaging of the responses of those with BN and BED to disorder-specific stimuli, such as food, is not extensively investigated. Furthermore, to our knowledge, there have been no previous published studies examining the neural response of individuals currently experiencing binge eating, to low energy foods. Our objective was to examine the neural responses to both low energy and high energy food images in three emotive categories (disgust; fear; and happy) in BN and BED participants.

Methods

Nineteen females with BN (n = 14) or BED (n = 5), comprising the binge eating group (BEG; N = 19), and 19 age-matched healthy control (HC)’s completed thorough clinical assessment prior to functional MRI (fMRI). Neural response to low energy and high energy foods and non-food images was compared between groups using whole-brain exploratory analyses, from which six regions of interest (ROI) were then selected: frontal, occipital, temporal, and parietal lobes; insula and cingulate.

Results

In response to low energy food images, the BEG demonstrated differential neural responses to all three low energy foods categories (disgust; fear; and happy) compared to HCs. Correlational analyses found a significant association between frequency of binge episodes and diminished temporal lobe and greater occipital lobe response. In response to high energy food images, compared to HC’s, the BEG demonstrated significantly decreased neural activity in response to all high energy food images. The HC’s had significantly greater neural activity in the limbic system, occipital lobe, temporal lobe, frontal lobe, and limbic system in response to high energy food images.

Conclusion

Results in the low energy food condition indicate that binge frequency may be related to increased aberrant neural responding. Furthermore, differences were found between groups in all ROI’s except the insula. The neural response seen in the BEG to disgust food images may indicate disengagement with this particular stimuli. In the high energy food condition, results demonstrate that neural activity in BN and BED patients may decrease in response to high energy foods, suggesting disengagement with foods that may be more consistent with those consumed during a binge eating episode.
Praying for a Miracle: Negative or Positive Impacts on Health Care?
Authors: Leal Miriam Martins , Nwora Emmanuel Ifeka , de Melo Gislane Ferreira , Freitas Marta Helena
Published: April 2022

The belief in miracle, as a modality of spiritual/religious coping (SRC) strategy in the face of stress and psychic suffering, has been discussed in psychological literature with regard to its positive or negative role on the health and well-being of patients and family members. In contemporary times, where pseudo-conflicts between religion and science should have been long overcome, there is still some tendency of interpreting belief in miracle – as the possibility of a cure granted by divine intervention, modifying the normal course of events in a bleak medical diagnosis – as having unhealthy impacts in the care and treatment of health. This position seeks to find a base in the three characteristics of hoping in a miracle, frequently pointed out by psychological literature: (a) it would imply a negation of reality instead of its confrontation; (b) it would be a coping strategy focused on emotion instead of the problem; (c) it would imply seeking to modify the supposed desire of God by extra-natural facts. In this study, we shall critically discuss this position and the dangers of its crystallization by the use of SRC scales in which the act of praying for a miracle is previously classified as a negative strategy. We revisit some tendencies in psychological literature about the subject, taking into consideration the various facets of miracle, sociocultural facts, elements of idiographic nature, and their profound outcomes in the lives of people especially in health contexts. We illustrate the dangers of a hasty generalization of the results of nomothetic studies about the role of belief in miracle with two examples of research in the Brazilian context: one carried out with pregnant women with fetal malformation and the other with family members caring for children and adolescents with cancer under chemotherapeutic treatment. In both studies, the results do not confirm the predominance of the negative aspects associated with the act of praying for a miracle, which we discuss and analyze in light of the phenomenological perspective. In this perspective, “pray for a miracle”, as experienced by patients and caregivers, can be recognized as an act of openness to life (instead of isolation in a bleak perspective), bolstering hope, and the resignification of reality in the psyche.
Case Report: Right Insular Stroke Causing Simultaneous Onset of a Functional Vestibular Disorder and Psychiatric Disorder—Persistent Postural–Perceptual Dizziness and Post–stroke Depression
Authors: Fipps David C. , Staab Jeffrey P. , Allen Nicholas D.
Published: April 2022

Introduction

Persistent postural–perceptual dizziness (PPPD) is a chronic functional vestibular disorder that can be precipitated by acquired brain injuries. Poststroke depression (PSD) is the most common psychiatric sequela of stroke, affecting 33% of stroke survivors. Pathophysiologic mechanisms of PPPD and PSD are not fully understood.

Case Report

A 40-year-old woman developed new, debilitating chronic dizziness exacerbated by her own motion and exposure to visual motion stimuli plus prolonged depressive symptoms, both beginning within days after a localized right insular stroke. A collaborative evaluation by specialists in neurology, otorhinolaryngology, optometry, and psychiatry concluded that the insular stroke caused simultaneous onset of PPPD and PSD.

Discussion

Prior case reports described short-lived vertigo following insular strokes, but no long-term vestibular symptoms without ongoing nystagmus or gait ataxia. In this case, chronic dizziness and motion sensitivity continued in the absence of focal neurologic deficits, invoking the possibility that changes in functioning of brain networks subserving spatial orientation persisted despite otherwise adequate recovery from the stroke, a mechanism previously proposed for PPPD. This case also reinforced prior work implicating pathways through the insula in PSD. Co-occurrence of PPPD and PSD offers insights into simultaneous functions of the insula in multiple networks in human brain.
Alternations in Dynamic and Static Functional Connectivity Density in Chronic Smokers
Authors: Yang Zhengui , Wen Mengmeng , Wei Yarui , Huang Huiyu , Zheng Ruiping , Wang Weijian , Gao Xinyu , Zhang Mengzhe , Cheng Jingliang , Han Shaoqiang , Zhang Yong
Published: April 2022

Previous studies have implicated abnormal functional coordination in brain regions of smokers. Neuroimaging studies demonstrated alternations in brain connectivity by using the resting-state functional connectivity (rsFC) method which arbitrarily chooses specific networks or seed regions as priori selections and cannot provide a full picture of the FC changes in chronic smokers. The aim of this study was to investigate the whole-brain functional coordination measured by functional connectivity density (FCD). As the variance of brain activity, dynamic FCD (dFCD) was performed to investigate dynamic changes of whole-brain integration in chronic smokers. In total, 120 chronic smokers and 56 nonsmokers were recruited, and static FCD and dFCD were performed to investigate aberrance of whole-brain functional coordination. Shared aberrance in visual areas has been found in both static and dFCD study in chronic smokers. Furthermore, the results exhibited that both heavy and light smokers demonstrated decreased dFCD in the visual cortex and left precuneus, and also increased dFCD in the right orbitofrontal cortex, left caudate, right putamen, and left thalamus compared with nonsmokers. In addition, alternations of dFCD have been found between heavy and light smokers. Furthermore, the dFCD variations showed significant positive correlation with smoking-related behaviors. The results demonstrated that chronic smokers not only have some initial areas, but also have some regions associated with severity of cigarette smoking. Lastly, dFCD could provide more subtle variations in chronic smokers, and the combination of static and dFCD may deepen our understanding of the brain alternations in chronic smokers.
A Literature Mini-Review of Transcranial Direct Current Stimulation in Schizophrenia
Authors: Stuchlíková Zuzana , Klírová Monika
Published: April 2022

Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation method that utilizes the effect of low-current on brain tissue. In recent years, the effect of transcranial direct current stimulation has been investigated as a therapeutic modality in various neuropsychiatric indications, one of them being schizophrenia. This article aims to provide an overview of the potential application and effect of tDCS in treating patients with schizophrenia. A literature search was performed using the PubMed, Web of Science, and Google Scholar databases for relevant research published from any date until December 2021. Eligible studies included those that used randomized controlled parallel-group design and focused on the use of transcranial direct current stimulation for the treatment of positive, negative, or cognitive symptoms of schizophrenia. Studies were divided into groups based on the focus of research and an overview is provided in separate sections and tables in the article. The original database search yielded 705 results out of which 27 randomized controlled trials met the eligibility criteria and were selected and used for the purpose of this article. In a review of the selected trials, transcranial direct current stimulation is a safe and well-tolerated method that appears to have the potential as an effective modality for the treatment of positive and negative schizophrenic symptoms and offers promising results in influencing cognition. However, ongoing research is needed to confirm these conclusions and to further specify distinct application parameters.
Trends in Mortality From Novel Psychoactive Substances as “Legal Highs”: Gender Differences in Manner of Death and Implications for Risk Differences for Women
Authors: Webb Lucy , Shi Xin , Goodair Christine , Cheeta Survjit
Published: April 2022

Introduction

This study aimed to examine drug-related deaths in the UK in which novel psychoactive substances (NPS) are an implicated substance, and to focus on female deaths in comparison with male deaths. While male overdoses dominate epidemiological statistics, there is an increase in female drug-related deaths and a narrowing of the gap between gender mortality rates which is to date unexplained.

Method

This study analyzed data from the National Programme for Substance Abuse Deaths (NPSAD) database that records drug-related deaths in the UK from coronial records. A dataset was constructed using parameters to capture all drug-related cases during the period 2007–2017 when NPS were legal and highly available in the UK, in order to capture deaths recorded among both regular and occasional drug users, and to include all cases recorded during that period regardless of NPS status in order to make comparisons. The final dataset comprised 10,159 cases, with 456 NPS-related deaths. Data for NPS and non-NPS were compared, and comparisons were made between cohorts by gender. The dataset also includes coronial narrative notes which allowed a qualitative analysis of NPS female deaths to add contextual explanation.

Results

The proportion of male NPS deaths is significantly higher than that for female NPS deaths but does not reflect the generalized difference between male and female drug-related mortality of this period studied. Demographic and outcome data by gender difference were significant for all drug-related deaths, but not for NPS-only deaths, indicating a greater homogeneity among NPS deaths by gender. Older women using NPS were more likely to have methadone or diazepam as another drug implicated and have established histories of drug misuse.

Conclusion

Where NPS have been used, differences in drug death profiles are less likely to be accounted for by gender than other demographic or behavioral differences more typically found in opiate deaths. The social and health problems of older women may be key characteristics that differentiate female deaths from male deaths. These findings also support evidence of increasing uptake of NPS among older established drug users that adds further risk to polydrug use.
Selling World Health Organization's Alcohol “Best Buys” and Other Recommended Interventions in an Urban Chinese Population: Public Acceptability of Alcohol Harms Reduction Strategies in Hong Kong
Authors: Yu Jiazhou , Dong Dong , Sumerlin Timothy S. , Goggins William B. , Feng Qi , Kim Jean H.
Published: April 2022

Background

To counter the harms caused by alcohol use, the World Health Organization (WHO) outlined a series of evidence-based recommendations, including the highly cost-effective “Best Buys” recommendations. While many Western countries have been actively introducing alcohol harms reduction strategies, it is unclear whether these cost-effective policies would be publicly acceptable in Asian regions with traditionally low alcohol consumption. This study examines the public acceptability of WHO-recommended alcohol harms reduction strategies in an Asian city with few extant alcohol regulations.

Methods

A cross-sectional telephone survey of Hong Kong Chinese residents aged 18–74 (n = 4,000) was conducted from January to August 2018. Respondents were asked about their perceptions of various WHO-recommended strategies and consequences of their implementation. After reducing the strategies into several policy categories by principal component analysis, multivariable linear regression was performed to identify factors associated with endorsement of the various policies.

Results

Among the “Best Buys”, introduction of moderate beer/wine taxes (68.7%) and shortened alcohol retail hours (51.9%) were the most supported while bans on event sponsorships (19.5%) and public drinking events (17.7%) were the least popular. Strategies targeting young drinkers were particularly highly supported. Males, younger adults, Non-abstainers, and those who believed in drinking's social benefits were less likely to endorse stringent control measures (p < 0.05). Adults with higher household income were less supportive, partially due to concerns about infringements on local economy, lifestyles, and economic freedom. Women and older people were generally more supportive, partially because they perceived these policies would lower alcohol-related harms.

Conclusion

In order to reduce barriers to implementing WHO-recommended strategies in the region, it is imperative to increase awareness of alcohol-related harms and to strengthen beliefs in the effectiveness of these countermeasures, especially among men, young adults, and drinkers.
Spatio-Temporal Disparity and Driving Forces of the Supply Level of Healthcare Service in the Yangtze River Delta
Authors: Li Zaijun , Hu Meijuan
Published: April 2022

The equalization of healthcare supply is not only related to the people's need for a better life, but can also provide a strong guarantee for the high-quality and sustainable development of the Yangtze River Delta integration. By using exploratory spatial analysis techniques, this study analyzed the spatio-temporal evolution characteristics and heterogeneous influence effects of the supply level of healthcare service in the Yangtze River Delta from 2007 to 2019. It was found that the supply level of healthcare service in the Yangtze River Delta had improved significantly. The differences in the supply level of healthcare service between cities had tended to narrow without polarization, and the supply level of healthcare service generally showed a high spatial pattern in the south delta and low spatial pattern in the north delta. The higher the supply level of healthcare service was, the weaker the interannual variability was. The supply level of healthcare service in the Yangtze River Delta region presented obvious spatial association and differentiated tendency of local high and low spatial clusters. The relative length and curvature of the supply level of healthcare service in the Yangtze River Delta generally presented a spatial pattern with low values in the northeast and high values in the southwest. Population density and urban-rural income gap generally exhibited negative spatio-temporal impact on the supply level of healthcare service across most cities. On the other hand, urbanization level and per capita disposable income generally had positive spatio-temporal impact on the supply level of healthcare service across most cities. Per capita gross domestic product (GDP) showed an increasingly positive spatio-temporal impact on the supply level of healthcare service across most cities. While per capita fiscal expenditure exhibited significantly negative impact on the supply level of healthcare service across most cities in space.
Revealing the Effectiveness of Tourism Development on Health in Asian Economies
Authors: Song Yun , Su Zhi-Wei , Tao Ran , Umut Alican
Published: April 2022

Most Asian economies consist of tourism attraction destinations. The traditional literature explores the cultural, social, and economic effects of tourism; thus, there exists a vacuum related to the impacts of tourism development on the human health of local people. Hence, the current study examines the impact of tourism development on health outcomes of the tourism-based selected Asian economies. The panel autoregressive distributed lag (ARDL) methodology is used to deduce the short-run and long-run impacts of tourism development on health outcomes. The results disclose that tourism activities insignificantly influence health outcomes in the short run. However, tourism development brings improvement in health outcomes in the long run. This research offers a new approach highlighting the significance of tourism development for human health and emphasizes the importance of tourism development for destination management and marketing.
Groundwater: Discovering Our Hidden Resource
Authors: Pearson Andrew , Aitchison-Earl Philippa
Published: April 2022

Have you ever wondered where the water in your tap comes from? Or why rivers still flow, and lakes can still be full, even when it has not rained for a long time? Or how people can get drinking water from a well in the middle of a dry, hot desert? The answer to these questions may be groundwater! Groundwater is underground, so we very rarely see it, but it is extremely important for billions of people. It gives us water for drinking and for producing food, and it provides habitats for animals. However, groundwater is also facing some big challenges, such as climate change, overuse, and pollution. We all need to do our best to protect groundwater and to spread the word to our families, friends, and governments.
Incorporating Blood Flow in Nerve Injury and Regeneration Assessment
Authors: Yeoh Stewart , Warner Wesley S. , Merchant Samer S. , Hsu Edward W. , Agoston Denes v. , Mahan Mark A.
Published: April 2022

Peripheral nerve injury is a significant public health challenge, with limited treatment options and potential lifelong impact on function. More than just an intrinsic part of nerve anatomy, the vascular network of nerves impact regeneration, including perfusion for metabolic demands, appropriate signaling and growth factors, and structural scaffolding for Schwann cell and axonal migration. However, the established nerve injury classification paradigm proposed by Sydney Sunderland in 1951 is based solely on hierarchical disruption to gross anatomical nerve structures and lacks further information regarding the state of cellular, metabolic, or inflammatory processes that are critical in determining regenerative outcomes. This review covers the anatomical structure of nerve-associated vasculature, and describes the biological processes that makes these vessels critical to successful end-organ reinnervation after severe nerve injuries. We then propose a theoretical framework that incorporates measurements of blood vessel perfusion and inflammation to unify perspectives on all mechanisms of nerve injury.
Developing Immune Profiles of Endangered Australian Sea Lion (Neophoca cinerea) Pups Within the Context of Endemic Hookworm (Uncinaria sanguinis) Infection
Authors: Meza Cerda María-Ignacia , Gray Rachael , Thomson Peter C. , Butcher Loreena , Simpson Kelly , Cameron Abby , Marcus Alan D. , Higgins Damien P.
Published: April 2022

As a top predator, the endangered Australian sea lion (Neophoca cinerea) is a sentinel of ecosystem change, where population trends can reflect broader shifts in the marine environment. The population of this endemic pinniped was historically diminished by commercial sealing, and recovery has been slowed by fishery interactions, disease and, potentially, pollutants. Hookworm infects 100% of neonatal pups and has been identified as a contributor to population decline. Here, a multivariable approach using traditional serological and novel molecular tools such as qPCR and ddPCR was used to examine immune phenotypes of developing Australian sea lion pups infected with the endemic hookworm (Uncinaria sanguinis) from two South Australian colonies. Results show changing immunophenotypes throughout the patent period of infection represented by pro-inflammatory cytokines (IL-6), IgG and acute-phase proteins. Although cytokines may prove useful as markers of resistance, in this study, IL-6 is determined to be an early biomarker of inflammation in Australian sea lion pups, excluding the alternative hypothesis. Additionally, immunological differences between animals from high- and low-intensity hookworm seasons, as well as ivermectin-treated animals, indicate hookworm infection modulation of the host immune response, as evidenced by a lower IL-6 mRNA expression in the non-treated groups. This study of the Australian sea lion is an example of an ecoimmunological approach to disease investigation, which can be applied to evaluate the impact of environmental and anthropogenic factors on susceptibility to infectious diseases in free-ranging species
New Insights for the Design of Bionic Robots: Adaptive Motion Adjustment Strategies During Feline Landings
Authors: Xu Datao , Zhou Huiyu , Jiang Xinyan , Li Shudong , Zhang Qiaolin , Baker Julien S. , Gu Yaodong
Published: April 2022

Felines have significant advantages in terms of sports energy efficiency and flexibility compared with other animals, especially in terms of jumping and landing. The biomechanical characteristics of a feline (cat) landing from different heights can provide new insights into bionic robot design based on research results and the needs of bionic engineering. The purpose of this work was to investigate the adaptive motion adjustment strategy of the cat landing using a machine learning algorithm and finite element analysis (FEA). In a bionic robot, there are considerations in the design of the mechanical legs. (1) The coordination mechanism of each joint should be adjusted intelligently according to the force at the bottom of each mechanical leg. Specifically, with the increase in force at the bottom of the mechanical leg, the main joint bearing the impact load gradually shifts from the distal joint to the proximal joint; (2) the hardness of the materials located around the center of each joint of the bionic mechanical leg should be strengthened to increase service life; (3) the center of gravity of the robot should be lowered and the robot posture should be kept forward as far as possible to reduce machine wear and improve robot operational accuracy.
Canine Geriatric Syndrome: A Framework for Advancing Research in Veterinary Geroscience
Authors: McKenzie Brennen A. , Chen Frances L. , Gruen Margaret E. , Olby Natasha J.
Published: April 2022

Biological aging is the single most important risk factor for disease, disability, and ultimately death in geriatric dogs. The effects of aging in companion dogs also impose significant financial and psychological burdens on their human caregivers. The underlying physiologic processes of canine aging may be occult, or early signs of aging may be ignored because of the misconception that biological aging is natural and therefore inevitable. The ability to detect, quantify, and mitigate the deleterious processes of canine aging would greatly enhance veterinary preventative medicine and animal welfare. In this paper we propose a new conceptual framework for aging in dogs, the Canine Geriatric Syndrome (CGS). CGS consists of the multiple, interrelated physical, functional, behavioral, and metabolic changes that characterize canine aging as well as the resulting clinical manifestations, including frailty, diminished quality of life, and age-associated disease. We also identify potential key components of a CGS assessment tool, a clinical instrument that would enable veterinarians to diagnose CGS and would facilitate the development and testing of interventions to prolong healthspan and lifespan in dogs by directly targeting the biological mechanisms of aging. There are many gaps in our knowledge of the mechanisms and phenotype of aging in dogs that must be bridged before a CGS assessment tool can be deployed. The conceptual framework of CGS should facilitate identifying these gaps and should stimulate research to better characterize the processes and effects of aging in dogs and to identify the most promising preventative strategies to target these.
The Biometric Parameters of Microgreen Crops Grown under Various Light Conditions
Authors: Frąszczak Barbara , Kula-Maximenko Monika
Published: April 2022

Microgreens are becoming increasingly popular both as horticultural crops and as vegetables consumed by humans. They are classified as foods of high nutritional value. Twenty-eight microgreens crops were grown in a growth chamber under fully controlled conditions in order to determine how different light treatments affected their growth rate. The plants were grown under three light sources emitting red/blue ratios of about 6.7, 0.6, and 1.6 units (Red light, Blue light, and R + B light, respectively). Apart from that, the spectrum contained 10% yellow and orange light and 10% green light. The fresh weight of the plants ranged from 8 (perilla) to 1052 mg (nasturtium), whereas the length ranged for the same plants from 2.0 to 26.2 cm. The nasturtium was particularly strongly distinguished from the other species by the high values of its biometric parameters. The fresh mass of most of the other microgreens ranged from 20 to 100 mg, whereas their height ranged from 5 to 8 cm. Red light caused a significant increase in the fresh and dry weights of more than half of the species. The light spectrum had a lesser influence on the length of the plants. The research results showed considerable differences in the dynamics of growth of commonly cultivated microgreens.
Investigating the Impact of Ultrasound, Microwave, and High-Pressure Processing of Milk on the Volatile Compounds and Sensory Properties of Cheddar Cheese
Authors: Munir Masooma , Nadeem Muhammad , Ali Barkat , Sultan Muhammad , Kanwal Rabia , Al-Jumayi Huda Abdalrahman , Algarni Eman Hassan Ahmed , Alnofeai Maged B. , Mahmoud Samy F.
Published: April 2022

Each cheese type has a unique flavor. A variety of compounds of various concentrations and different chemical classes contribute to this flavor. In the present study, the effect of processing techniques (ultrasonication (US), high pressure processing (HPP), microwave (MW)) on the flavors and sensory properties of milk and cheese was investigated. Samples of treated and untreated milk and cheese were analyzed for volatile compounds (including aldehydes, ketones, alcohols, fatty acids, and hydrocarbons). Significant variation was observed, and the results of sensory evaluation showed that cheese prepared from HPP and US-1 (21 J/g) secured higher sensory scores when compared to cheese prepared from US-2 (41 J/g), MW treatment, and the control. Variations in volatile profiles of milk and cheese were also evident according to the treatment process i.e., dodecanoic acid, octanoic acid, heptanoic acid, and nonanoic acid. Valeric acid was present only in US-1- (21 J/g) and US-2- (41 J/g) treated cheese, which is responsible for burnt and metallic flavors in milk and cheese. Butanoic acid, heptanal, heptanone, and butanediol were present in HPP, while ethyl butanoate, decanone, and 2,3-butanedione were present in microwave-treated milk. In a nutshell, the results of volatile compounds and sensory scores of cheeses are analogous, which shows that ultrasonication with high power output has some drawback because of the burnt and metallic flavor.
Opportunities and Challenges for Lebanese Horticultural Producers Linked to Corporate Buyers
Authors: Mukahhal Walid , Abebe Gumataw Kifle , Bahn Rachel A.
Published: April 2022

This paper aims to analyze procurement decisions and contractual arrangements in the horticultural supply chain and evaluate opportunities for and challenges of horticultural producers linked to supermarkets and corporate restaurants in Lebanon. Accordingly, in-depth, semi-structured interviews were conducted with key horticultural supply chain actors in Lebanon. The study finds that corporate restaurants offer more opportunities for large horticultural producers and suppliers than supermarkets. Yet, corporate restaurants have more stringent quality requirements, as demonstrated by food safety certifications, and their contractual relationships are binding, symbiotic, and formal. Supermarkets source most of their products from wholesale markets and have opportunistic, non-binding relationships with their suppliers. In sum, the nature of the business relationships between horticultural producers and suppliers and corporate buyers depends on the ability of the producers to meet the quality requirements of the latter. Although corporate buyers have shown some interest in the local produce, they are yet to invest in local supplier development initiatives to enhance the capabilities of producers. Instead, corporate buyers resort to imports when the local producers fail to meet the quality standards or required volumes. The study suggests several alternative routes to enhance the market position of horticultural producers and suppliers in Lebanon.