bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate risk assessment of the Tangier-Tetouan-Al Hoceima coastal Region (Morocco)
Authors: Agharroud Kamal , Puddu Manuela , Ivčević Ante , Satta Alessio , Kolker Alexander S. , Snoussi Maria
Published: April 2023

Coastal zones occupy a prominent position in the sustainable management perspective of Tangier-Tetouan-Al Hoceima (TTA) region because they accommodate a majority of the region’s population and contribute to the economic wellbeing of local communities. High demographic and economic pressures associated to climatic and environmental factors increase and intensify the vulnerability of these coastal areas. The latter are severely affected by climate change implications in the course of time, which lead to damage and loss in coastal low-lying zones. In practice, the risks related to climate change, as coastal risks, are frequently addressed, and assessing coastal risk in the context of climate change is a research priority. The aim of this work is to evaluate the flooding risk of TTA coasts, taking into account the inundation level related to the conditions of extreme wave (return period of 100-year) and extreme sea level rise. We firstly defined the coastal hazard zone that corresponds to the maximum inundation level of 13 m for the whole area. We then applied a Coastal Risk Index application at the Local Scale (CRI-LS) methodology to calculate forcing, vulnerability, exposure and risk indices using nineteen physical, environmental and socioeconomical variables. Findings show that coastal hazard zone of Tangier-Tetouan-Al Hoceima region is extremely exposed to coastal forcing. More than 50% of the hazard zones indicates highly vulnerable zones and highest exposure is generally focused on the most populated urban zones. In the light of this, the coastal risk mapping shows hotspot zones in terms of climate change-related coastal risks located at Tangier Bay, south of Tangier city, Fnideq and Martil coasts, Tetouan city and north of Ksar El Kbir city. This paper corresponds to a useful support that can help policy-makers in decision-making to quietly follow coastal planning and management processes and participate in preserving coastal areas for future generations, which support the sustainable development goals of Agenda 2030 started by the United Nations with the goal of eradicating all kinds of poverty.
Individualized assessment predictive models for risk and overall survival in elderly patients of primary kidney cancer with bone metastases: A large population-based study
Authors: Jiang Liming , Tong Yuexin , Jiang Jiajia , Zhao Dongxu
Published: April 2023

Background

Elderly people are at high risk of metastatic kidney cancer (KC), and, the bone is one of the most common metastatic sites for metastatic KC. However, studies on diagnostic and prognostic prediction models for bone metastases (BM) in elderly KC patients are still vacant. Therefore, it is necessary to establish new diagnostic and prognostic nomograms.

Methods

We downloaded the data of all KC patients aged more than 65 years during 2010–2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses were used to study independent risk factors of BM in elderly KC patients. Univariate and multivariate Cox regression analysis for the study of independent prognostic factors in elderly KCBM patients. Survival differences were studied using Kaplan–Meier (K–M) survival analysis. The predictive efficacy and clinical utility of nomograms were assessed by receiver operating characteristic (ROC) curve, the area under curve (AUC), calibration curve, and decision curve analysis (DCA).

Results

A final total of 17,404 elderly KC patients (training set: n = 12,184, validation set: n = 5,220) were included to study the risk of BM. 394 elderly KCBM patients (training set: n = 278, validation set: n = 116) were included to study the overall survival (OS). Age, histological type, tumor size, grade, T/N stage and brain/liver/lung metastasis were identified as independent risk factors for developing BM in elderly KC patients. Surgery, lung/liver metastasis and T stage were identified as independent prognostic factors in elderly KCBM patients. The diagnostic nomogram had AUCs of 0.859 and 0.850 in the training and validation sets, respectively. The AUCs of the prognostic nomogram in predicting OS at 12, 24 and 36 months were: training set (0.742, 0.775, 0.787), and validation set (0.721, 0.827, 0.799), respectively. The calibration curve and DCA also showed excellent clinical utility of the two nomograms.

Conclusion

Two new nomograms were constructed and validated to predict the risk of developing BM in elderly KC patients and 12-, 24-, and 36-months OS in elderly KCBM patients. These models can help surgeons provide more comprehensive and personalized clinical management programs for this population.
Application of DCE-MRI radiomics signature analysis in differentiating molecular subtypes of luminal and non-luminal breast cancer
Authors: Huang Ting , Fan Bing , Qiu Yingying , Zhang Rui , Wang Xiaolian , Wang Chaoxiong , Lin Huashan , Yan Ting , Dong Wentao
Published: April 2023

Background

The goal of this study was to develop and validate a radiomics signature based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) preoperatively differentiating luminal and non-luminal molecular subtypes in patients with invasive breast cancer.

Methods

One hundred and thirty-five invasive breast cancer patients with luminal (n = 78) and non-luminal (n = 57) molecular subtypes were divided into training set (n = 95) and testing set (n = 40) in a 7:3 ratio. Demographics and MRI radiological features were used to construct clinical risk factors. Radiomics signature was constructed by extracting radiomics features from the second phase of DCE-MRI images and radiomics score (rad-score) was calculated. Finally, the prediction performance was evaluated in terms of calibration, discrimination, and clinical usefulness.

Results

Multivariate logistic regression analysis showed that no clinical risk factors were independent predictors of luminal and non-luminal molecular subtypes in invasive breast cancer patients. Meanwhile, the radiomics signature showed good discrimination in the training set (AUC, 0.86; 95% CI, 0.78–0.93) and the testing set (AUC, 0.80; 95% CI, 0.65–0.95).

Conclusion

The DCE-MRI radiomics signature is a promising tool to discrimination luminal and non-luminal molecular subtypes in invasive breast cancer patients preoperatively and noninvasively.
The clinical efficacy of melatonin in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials
Authors: Huang Po-Yu , Wu Jheng-Yan , Liu Ting-Hui , Tsai Ya-Wen , Chen Po-Tsang , Liao Chia-Te , Toh Han Siong
Published: April 2023

Background

The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide, with cytokine storm leading to exaggerating immune response, multi-organ dysfunction and death. Melatonin has been shown to have anti-inflammatory and immunomodulatory effects and its effect on COVID-19 clinical outcomes is controversial. This study aimed to conduct a meta-analysis to evaluate the impact of melatonin on COVID-19 patients.

Methods

PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched without any language or publication year limitations from inception to 15 Nov 2022. Randomized controlled trials (RCTs) using melatonin as therapy in COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included were the recovery rate of clinical symptoms, changes in the inflammatory markers like C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR). A random-effects model was applied for meta-analyses, and further subgroup and sensitivity analyses were also conducted.

Results

A total of nine RCTs with 718 subjects were included. Five studies using melatonin with the primary outcome were analyzed, and the pooled results showed no significant difference in mortality between melatonin and control groups with high heterogeneity across studies identified (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.47–1.11, p = 0.14, I2 = 82%). However, subgroup analyses revealed statistically significant effects in patients aged under 55 years (RR 0.71, 95% CI 0.62–0.82, p < 0.01) and in patients treated for more than 10 days (RR 0.07, 95% CI 0.01–0.53, p = 0.01). The recovery rate of clinical symptoms and changes in CRP, ESR, and NLR were not statistically significant. No serious adverse effects were reported from melatonin use.

Conclusion

In conclusion, based on low certainty of evidence, the study concluded that melatonin therapy does not significantly reduce mortality in COVID-19 patients, but there are possible benefits in patients under 55 years or treated for more than 10 days. With a very low certainty of evidence, we found no significant difference in the recovery rate of COVID-19 related symptoms or inflammatory markers in current studies. Further studies with larger sample sizes are warranted to determine the possible efficacy of melatonin on COVID-19 patients.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022351424.
A new pathogenic isolate of Kocuria kristinae identified for the first time in the marine fish Larimichthys crocea
Authors: Meng Xiangyu , Chen Fangyi , Xiong Ming , Hao Hua , Wang Ke-Jian
Published: April 2023

In recent years, new emerging pathogenic microorganisms have frequently appeared in animals, including marine fish, possibly due to climate change, anthropogenic activities, and even cross-species transmission of pathogenic microorganisms among animals or between animals and humans, which poses a serious issue for preventive medicine. In this study, a bacterium was clearly characterized among 64 isolates from the gills of diseased large yellow croaker Larimichthys crocea that were raised in marine aquaculture. This strain was identified as K. kristinae by biochemical tests with a VITEK 2.0 analysis system and 16S rRNA sequencing and named K. kristinae_LC. The potential genes that might encode virulence-factors were widely screened through sequence analysis of the whole genome of K. kristinae_LC. Many genes involved in the two-component system and drug-resistance were also annotated. In addition, 104 unique genes in K. kristinae_LC were identified by pan genome analysis with the genomes of this strain from five different origins (woodpecker, medical resource, environment, and marine sponge reef) and the analysis results demonstrated that their predicted functions might be associated with adaptation to living conditions such as higher salinity, complex marine biomes, and low temperature. A significant difference in genomic organization was found among the K. kristinae strains that might be related to their hosts living in different environments. The animal regression test for this new bacterial isolate was carried out using L. crocea, and the results showed that this bacterium could cause the death of L. crocea and that the fish mortality was dose-dependent within 5 days post infection, indicating the pathogenicity of K. kristinae_LC to marine fish. Since K. kristinae has been reported as a pathogen for humans and bovines, in our study, we revealed a new isolate of K. kristinae_LC from marine fish for the first time, suggesting the potentiality of cross-species transmission among animals or from marine animals to humans, from which we would gain insight to help in future public prevention strategies for new emerging pathogens.
A community outbreak of Legionnaires’ disease caused by outdoor hot tubs for private use in a hotel
Authors: Gumá Mercedes , Drasar Vladimir , Santandreu Beatriz , Cano Rosa , Afshar Baharak , Nicolau Antonio , Bennassar Magdalena , Barrio Jorge del , Crespi Pau , Crespi Sebastian
Published: April 2023

During the period October–November 2017, an outbreak of Legionnaires’ disease involving 27 cases occurred in the tourist area of Palmanova (Mallorca, Spain). The majority of cases were reported by the European Centre of Disease Prevention and Control (ECDC) as travel associated cases of Legionnaires’ disease (TALD). Most cases belonged to different hotel cluster alerts. No cases were reported among the local population residing in the area. All tourist establishments associated with one or more TALD cases were inspected and sampled by public health inspectors. All relevant sources of aerosol emission detected were investigated and sampled. The absence of active cooling towers in the affected area was verified, by documents and on-site. Samples from hot tubs for private use located on the terraces of the penthouse rooms of a hotel in the area were included in the study. Extremely high concentrations (> 106 CFU/l) of Legionella pneumophila, including the outbreak strain, were found in the hot tubs of vacant rooms of this hotel thus identifying the probable source of infection. Meteorological situation may have contributed to the geographical distribution pattern of this outbreak. In conclusion, hot tubs for private use located outdoors should be considered when investigating community outbreaks of Legionnaires’ disease of unclear origin.
Associations between anxiety, depression with migraine, and migraine-related burdens
Authors: Duan Shaojie , Ren Zhiying , Xia Hui , Wang Ziyao , Zheng Tao , Li Guanglu , Liu Lei , Liu Zunjing
Published: April 2023

Background

Anxiety and depression are the most common psychiatric comorbidities in migraine, but their impact on the risk of developing migraine and their gender and age differences are unclear, and research on their associations with migraine-related burdens are limited.

Objective

To systematically explore the association between anxiety and depression with migraine and migraine-related burdens, including the risk of developing migraine, as well as migraine frequency, severity, disability, headache impact, quality of life and sleep quality.

Methods

A total of 170 migraineurs and 85 sex-and age-matched healthy control subjects were recruited consecutively for this study. Anxiety and depression were assessed using Zung’s Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS), respectively. Logistic regression and linear regression analyses were used to explore the associations between anxiety and depression with migraine and its burdens. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SAS score and SDS score on migraine and its severe burdens.

Results

After adjusting for confounders, anxiety and depression remained significantly associated with an increased risk of developing migraine, with odds ratios of 5.186 (95% CI:1.755–15.322) and 3.147 (95% CI:1.387–7.141), respectively. Meanwhile, there were significant additive interactions between the association of anxiety and depression with the risk of developing migraine in gender and age (P for interaction <0.05), and the stronger correlations were found in participants with an age ≤ 36 years old and females. In addition, anxiety and depression were significantly independently associated with the migraine frequency, severity, disability, headache impact, quality of life, and sleep quality in migraine patients (P trend <0.05). The area under the ROC curve (AUC) of SAS score in predicting developing migraine was significantly higher than that of SDS score [0.749 (95% CI: 0.691–0.801) vs. 0.633 (95% CI: 0.571–0.692), p < 0.0001].

Conclusion

Anxiety and depression were significantly independently associated with the increased risk of migraine and migraine-related burdens. Enhanced assessment of SAS score and SDS score is of great clinical value for the early prevention and treatment of migraine and its burdens.
NeuroWRAP: integrating, validating, and sharing neurodata analysis workflows
Authors: Bowen Zac , Magnusson Gudjon , Diep Madeline , Ayyangar Ujjwal , Smirnov Aleksandr , Kanold Patrick O. , Losert Wolfgang
Published: April 2023

Multiphoton calcium imaging is one of the most powerful tools in modern neuroscience. However, multiphoton data require significant pre-processing of images and post-processing of extracted signals. As a result, many algorithms and pipelines have been developed for the analysis of multiphoton data, particularly two-photon imaging data. Most current studies use one of several algorithms and pipelines that are published and publicly available, and add customized upstream and downstream analysis elements to fit the needs of individual researchers. The vast differences in algorithm choices, parameter settings, pipeline composition, and data sources combine to make collaboration difficult, and raise questions about the reproducibility and robustness of experimental results. We present our solution, called NeuroWRAP (www.neurowrap.org), which is a tool that wraps multiple published algorithms together, and enables integration of custom algorithms. It enables development of collaborative, shareable custom workflows and reproducible data analysis for multiphoton calcium imaging data enabling easy collaboration between researchers. NeuroWRAP implements an approach to evaluate the sensitivity and robustness of the configured pipelines. When this sensitivity analysis is applied to a crucial step of image analysis, cell segmentation, we find a substantial difference between two popular workflows, CaImAn and Suite2p. NeuroWRAP harnesses this difference by introducing consensus analysis, utilizing two workflows in conjunction to significantly increase the trustworthiness and robustness of cell segmentation results.
The effects of nutritional supplementation on older sarcopenic individuals who engage in resistance training: a meta-analysis
Authors: Song Zixian , Pan Tingting , Tong Xu , Yang Ying , Zhang Ze
Published: April 2023

Objective

Sarcopenia is a typical age-related disorder characterized by loss of muscle mass, strength, and physical function. Resistance training has a noticeable effect on sarcopenia, but there is no consensus on whether nutritional supplements can boost this effect. We conducted a meta-analysis of relevant literature to investigate the therapeutic effect of resistance training combined with nutrition intervention on sarcopenia compared with resistance training alone.

Methods

Cochrane Library, PubMed, Web of Science, Embase, Sinomed, CNKI, VIP, and Wanfang Data were searched for relevant studies on resistance training combined with nutritional intervention for aging adults with sarcopenia. The retrieval period ranged from the inception of the databases to May 24, 2022. Literature screening and information extraction were performed by two researchers. The Physiotherapy Evidence Database (PEDro) scale was adopted for literature quality evaluation and Stata 15.0 software for analysis.

Results

Twelve clinical trials were included, involving 713 older adults diagnosed with sarcopenia, of whom 361 were assigned to the experimental group and 352 to the control group. Compared with the control group, grip strength of the experimental group was substantially elevated [WMD = 1.87, 95% CI (0.01, 3.74), P = 0.049]. Subgroup analysis demonstrated that vitamin D and protein increased grip strength and gait speed. There were no significant improvement in grip strength and gait speed in the protein and vitamin D free subgroup.

Conclusions

This meta-analysis demonstrated that resistance training combined with additional nutritional supplementation, especially compound nutritional supplements that included protein and vitamin D, might further enhance grip strength rather than muscle mass in older adults with sarcopenia.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022346734.
Virtual screening of ultra-large chemical libraries identifies cell-permeable small-molecule inhibitors of a “non-druggable” target, STAT3 N-terminal domain
Authors: Bonilla Pedro Andrade , Hoop Cody L. , Stefanisko Karen , Tarasov Sergey G. , Sinha Sourav , Nicklaus Marc C. , Tarasova Nadya I.
Published: April 2023

STAT3 N-terminal domain is a promising molecular target for cancer treatment and modulation of immune responses. However, STAT3 is localized in the cytoplasm, mitochondria, and nuclei, and thus, is inaccessible to therapeutic antibodies. Its N-terminal domain lacks deep pockets on the surface and represents a typical “non-druggable” protein. In order to successfully identify potent and selective inhibitors of the domain, we have used virtual screening of billion structure-sized virtual libraries of make-on-demand screening samples. The results suggest that the expansion of accessible chemical space by cutting-edge ultra-large virtual compound databases can lead to successful development of small molecule drugs for hard-to-target intracellular proteins.
Fibrodysplasia ossificans progressiva in Hong Kong—A case report series
Authors: Chan Joshua Chun Ki , Kuong Evelyn Eugenie , Chan Joyce Pui Kwan , Luk Ho Ming , Fung Jasmine Lee Fong , Tung Joanna Yuet-ling , Chung Brian Hon Yin
Published: April 2023

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare condition. The diagnosis could be challenging due to its rarity and non-specific presenting symptoms. However, early diagnosis and appropriate management help in preserving patients' function and quality of life. Herein, we report the diagnostic journeys and clinical courses of 8 patients with FOP in Hong Kong and illustrate the challenges involved.
Clinical efficacy analysis of paxlovid in children with hematological diseases infected with the omicron SARS-CoV-2 new variant
Authors: Li Yixian , Liu Yong , Wen Luping , Chen Hui , Wang Wenqing , Tian Mengyao , Cheng Yucai , Xue Hongman , Chen Chun
Published: April 2023

Objective

To summarize the clinical characteristics of children with hematological malignancies co-infected with novel coronavirus and explore the safety and effectiveness of Paxlovid treatment.

Methods

From December 10, 2022, to January 20, 2023, the clinical data of children with hematological diseases diagnosed with novel coronavirus infection in the outpatient and emergency department of the Seventh Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed.

Results

According to whether to give paxlovid or not, it is divided into group A (paxlovid group) and group B (non-paxlovid group). The length of fever was 1–6 days in group A and 0–3 days in group B. The viral clearance time was shorter in group A than in group B. The inflammatory indexes CRP and PCT were significantly higher in group A than in group B (P < 0.05). Twenty patients were followed up for 1 month after leaving the hospital, and there were 5 cases of reappearance of fever, 1 case of increased sleep, 1 case of physical fatigue and 1 case of loss of appetite within 2 weeks.

Conclusions

Paxlovid has no apparent adverse reactions in children 12 years old and younger with underlying hematological diseases infected with the new coronavirus. Focusing on the interaction between paxlovid and other drugs is necessary during the treatment.
Post-transplant donor-specific anti-HLA antibodies with a higher mean fluorescence intensity are associated with graft fibrosis in pediatric living donor liver transplantation
Authors: Goto Ryoichi , Fukasaku Yasutomo , Ganchiku Yoshikazu , Kawamura Norio , Watanabe Masaaki , Ota Takuji , Hatanaka Kanako C. , Suzuki Tomomi , Shimamura Tsuyoshi , Taketomi Akinobu
Published: April 2023

The roles of post-transplant anti-HLA donor specific antibody (DSA) in pediatric liver transplantation (LT), including therapeutic strategies, remain controversial. This study aimed to identify the risks of post-transplant DSA for graft fibrosis progression in pediatric living donor LT (LDLT). We retrospectively evaluated 88 LDLT pediatric cases between December 1995 and November 2019. DSAs were assessed with single antigen bead test. Graft fibrosis was histopathologically scored with METAVIR and the centrilobular sinusoidal fibrosis system. Post-transplant DSAs were detected in 37 (52.9%) cases at 10.8 (1.3–26.9) years post-LDLT. The histopathological examination of 32 pediatric cases with post-transplant DSA revealed that 7 (21.9%) with a high DSA-MFI (≥9,378) showed graft fibrosis progression (≥F2). No graft fibrosis was observed in the subjects with a low DSA-MFI. The risk factors for developing graft fibrosis in pediatric cases with post-transplant DSA were an older graft age (>46.5 years old), lower platelet count (<10.7 × 104/ml) and higher Fib4 index (>0.7807, recipient age; >1.8952, donor age). Limited efficacy of additional immunosuppressants was observed in DSA positive pediatric cases. In conclusion, pediatric cases with a high DSA-MFI and risk factors should undergo a histological examination. The appropriate treatment for post-transplant DSA in pediatric LT needs to be determined.
Immunohistochemical, pharmacovigilance, and omics analyses reveal the involvement of ATP-sensitive K+ channel subunits in cancers: role in drug–disease interactions
Authors: Maqoud Fatima , Zizzo Nicola , Attimonelli Marcella , Tinelli Antonella , Passantino Giuseppe , Antonacci Marina , Ranieri Girolamo , Tricarico Domenico
Published: April 2023

Background: ATP-sensitive-K+ channels (KATP) are involved in diseases, but their role in cancer is poorly described. Pituitary macroadenoma has been observed in Cantu’ syndrome (C.S.), which is associated with the gain-of-function mutations of the ABCC9 and KCNJ8 genes. We tested the role of the ABCC8/Sur1, ABCC9/Sur2A/B, KCNJ11/Kir6.2, and KCNJ8/Kir6.1 genes experimentally in a minoxidil-induced renal tumor in male rats and in the female canine breast cancer, a spontaneous animal model of disease, and in the pharmacovigilance and omics databases.

Methods: We performed biopsies from renal tissues of male rats (N = 5) following a sub-chronic high dosing topical administration of minoxidil (0.777–77.7 mg/kg/day) and from breast tissues of female dogs for diagnosis (N = 23) that were analyzed by immunohistochemistry. Pharmacovigilance and omics data were extracted from EudraVigilance and omics databases, respectively.

Results: An elevated immunohistochemical reactivity to Sur2A-mAb was detected in the cytosol of the Ki67+/G3 cells other than in the surface membrane in the minoxidil-induced renal tumor and the breast tumor samples. KCNJ11, KCNJ8, and ABCC9 genes are upregulated in cancers but ABCC8 is downregulated. The Kir6.2-Sur2A/B-channel opener minoxidil showed 23 case reports of breast cancer and one case of ovarian cancer in line with omics data reporting, respectively, and the negative and positive prognostic roles of the ABCC9 gene in these cancers. Sulfonylureas and glinides blocking the pancreatic Kir6.2-Sur1 subunits showed a higher risk for pancreatic cancer in line with the positive prognostic role of the ABCC8 gene but low risks for common cancers. Glibenclamide, repaglinide, and glimepiride show a lower cancer risk within the KATP channel blockers. The Kir6.2-Sur1 opener diazoxide shows no cancer reactions.

Conclusion: An elevated expression of the Sur2A subunit was found in proliferating cells in two animal models of cancer. Immunohistochemistry/omics/pharmacovigilance data reveal the role of the Kir6.1/2-Sur2A/B subunits as a drug target in breast/renal cancers and in C.S.
Immune-enhancing activity of polysaccharides and flavonoids derived from Phellinus igniarius YASH1
Authors: Zhu Xiaoya , Guo Ruirui , Su Xiayu , Shang Kun , Tan Conglian , Ma Junheng , Zhang Yuemeng , Lin Dan , Ma Yueran , Zhou Min , Yang Jiale , Wu Qiqi , Sun Jiale , Wang Zhuoling , Guo Yuyue , Su Ruifan , Cui Xiangyi , Han Jiming , Lü Yuhong , Yue Changwu
Published: April 2023

Introduction:Phellinus igniarius (P. igniarius) (Sanghuang) is a widely used traditional Chinese medicine fungus, and its natural products have great potential for clinical application in immune enhancement. This study aimed to explore the immune-enhancing activity and underlying mechanisms of the polysaccharides and flavonoids derived from Phellinus igniarius (P. igniarius) and to provide a theoretical and experimental basis for the development of novel drugs.

Methods: Wild P. igniarius YASH1 from the Loess Plateau in Yan’an region was collected, and polysaccharides and total flavonoids were extracted, isolated and identified from mycelium and sporophore. In vitro antioxidant activity was detected through the scavenging activity of hydroxyl radicals and total antioxidant capacity. Cell Counting Kit-8 and trypan blue detection kit were used to detect the effect of extract polysaccharides and flavonoids on the proliferation and phagocytosis ability of immune cells. To assess the effect of the drugs on cytokine secretion by immune cells and immune recovery in immunocompromised mice, the expression of interleukin (IL)-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were examined at the cellular and animal levels. The species composition, abundance of gut microbiota and the altered content of short-chain fatty acids in the feces were analyzed to elucidate the possible mechanisms of drugs by 16S ribosomal RNA (rRNA) amplifiers sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: Both polysaccharides and flavonoids derived from mycelium or sporophore had antioxidant activity and may stimulate the expression and secretion of IL-2, IL-6, and IFN-γ in immune cells while inhibiting TNF-α expression and secretion and increasing IL-2, IL-6, and IFN- γ expression levels in mice. Furthermore, polysaccharides and flavonoids from mycelium and sporophore showed different effects on the metabolic response of intestinal short-chain fatty acids (SCFAs) in mice, and the use of these drugs remarkably changed the species composition and abundance of intestinal flora in mice.

Discussion: Polysaccharides and flavonoids from P. igniarius YASH1 mycelium and sporophore have in vitro antioxidant activity, and they affect the promotion of cell proliferation, stimulation of IL-2, IL-6, and IFN-γ secretion, and inhibition of TNF-α expression in immune cells. Polysaccharides and flavonoids from P. igniarius YASH1 may enhance immunity in immunocompromised mice and remarkably affect the intestinal flora and content of SCFAs.
Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery
Authors: Sunildutt Naina , Parihar Pratibha , Chethikkattuveli Salih Abdul Rahim , Lee Sang Ho , Choi Kyung Hyun
Published: April 2023

The inefficiency of existing animal models to precisely predict human pharmacological effects is the root reason for drug development failure. Microphysiological system/organ-on-a-chip technology (organ-on-a-chip platform) is a microfluidic device cultured with human living cells under specific organ shear stress which can faithfully replicate human organ-body level pathophysiology. This emerging organ-on-chip platform can be a remarkable alternative for animal models with a broad range of purposes in drug testing and precision medicine. Here, we review the parameters employed in using organ on chip platform as a plot mimic diseases, genetic disorders, drug toxicity effects in different organs, biomarker identification, and drug discoveries. Additionally, we address the current challenges of the organ-on-chip platform that should be overcome to be accepted by drug regulatory agencies and pharmaceutical industries. Moreover, we highlight the future direction of the organ-on-chip platform parameters for enhancing and accelerating drug discoveries and personalized medicine.
Dose- and time-dependent renoprotection of Angelica sinensis in patients with chronic kidney disease: A longitudinal cohort study
Authors: Chen Hsiao-Tien , Yu Ben-Hui , Yeh Ming-Hsien , Hung Shih-Kai , Chen Yi-Chun
Published: April 2023

Background:Based on their anti-oxidative and anti-fibrotic properties,Angelica sinensis(Oliv.) Diels roots [Apiaceae; Radix Angelicae sinensis] (Danggui [abbreviated as S in the context]),Astragalus membranaceus(Fisch.) Bunge [Fabaceae;Astragalus membranaceus] (Huangqi [A]),Rheum palmatumL. [Polygonaceae; Rheum palmatum] (Dahuang [R]), andSalvia miltiorrhizaBunge [Lamiaceae; Salvia miltiorrhiza Bunge radix et rhizoma] (Danshen [D]) are potential renoprotective Chinese herbal medicines (CHMs). Renoprotection using ARD alone for the treatment of chronic kidney disease (CKD) has been documented in pre-clinical, clinical, and meta-analysis research; however, only pre-clinical data are available for the use of S alone. Moreover, with an increasing number of CKD patients taking prescribed CHMs, hyperkalemia risk remains unclear.

Methods:This study retrospectively analyzed national health insurance claims data in 2001–2017. Propensity score matching was used to analyze renal and survival outcomes and the dose-response effects of S without ARD use in 18,348 new S users, 9,174 new ARD users, and 36,696 non-users. Cox proportional hazard regression was used to investigate adjusted hazard ratios (aHRs) for end-stage renal disease (ESRD) in the presence of competing mortality and death. The additive effect of the S herb in single form to compounds was also analyzed. Additionally, to analyze hyperkalemia risk, an exact match on each covariate was used to include 42,265 new CHM users and non-users, while Poisson regression was used to estimate adjusted incidence rate ratios (aIRRs) of hyperkalemia of prescribed CHMs.

Results:S users and ARD users were associated with aHRs of 0.77 (95% confidence interval; 0.69–0.86) and 1.04 (0.91–1.19), respectively, for ESRD and 0.55 (0.53–0.57) and 0.71 (0.67–0.75), respectively, for death. The renal and survival benefits of S use were consistent in several sensitivity analyses. The dose- and time-dependent renoprotection and dose-dependent survival benefits were observed for S use. The top two additive renoprotective collocations of the S herb in compounds were Xue-Fu-Zhu-Yu-Tang and Shen-Tong-Zhu-Yu-Tang, followed by Shu-Jing-Huo-Xue-Tang and Shen-Tong-Zhu-Yu-Tang. Moreover, CHM users were associated with aIRRs of 0.34 (0.31–0.37) for hyperkalemia.

Conclusion:This study suggests dose- and time-dependent renoprotection and dose-dependent survival benefits of the S herb in compounds and no increased hyperkalemia risk of the prescribed CHMs in CKD patients.
Physical exercise, health, and disease treatment: The role of macrophages
Authors: Callegari Irineu O. M. , Rocha Guilherme Z. , Oliveira Alexandre G.
Published: April 2023

Subclinical inflammation is linked to comorbidities and risk factors, consolidating the diagnosis of chronic non-communicable diseases, such as insulin resistance, atherosclerosis, hepatic steatosis, and some types of cancer. In this context, the role of macrophages is highlighted as a marker of inflammation as well as for the high power of plasticity of these cells. Macrophages can be activated in a wide range between classical or proinflammatory, named M1, and alternative or anti-inflammatory, also known as M2 polarization. All nuances between M1 and M2 macrophages orchestrate the immune response by secreting different sets of chemokines, while M1 cells promote Th1 response, the M2 macrophages recruit Th2 and Tregs lymphocytes. In turn, physical exercise has been a faithful tool in combating the proinflammatory phenotype of macrophages. This review proposes to investigate the cellular and molecular mechanisms in which physical exercise can help control inflammation and infiltration of macrophages within the non-communicable diseases scope. During obesity progress, proinflammatory macrophages predominate in adipose tissue inflammation, which reduces insulin sensitivity until the development of type 2 diabetes, progression of atherosclerosis, and diagnosis of non-alcoholic fatty liver disease. In this case, physical activity restores the balance between the proinflammatory/anti-inflammatory macrophage ratio, reducing the level of meta-inflammation. In the case of cancer, the tumor microenvironment is compatible with a high level of hypoxia, which contributes to the advancement of the disease. However, exercise increases the level of oxygen supply, favoring macrophage polarization in favor of disease regression.
Elastin haploinsufficiency accelerates age-related structural and functional changes in the renal microvasculature and impairment of renal hemodynamics in female mice
Authors: Dixon Alethia J. , Osei-Owusu Patrick
Published: April 2023

Age-related decline in functional elastin is associated with increased arterial stiffness, a known risk factor for developing cardiovascular disease. While the contribution of elastin insufficiency to the stiffening of conduit arteries is well described, little is known about the impact on the structure and function of the resistance vasculature, which contributes to total peripheral resistance and the regulation of organ perfusion. In this study, we determined how elastin insufficiency impinges on age-related changes in the structure and biomechanical properties of the renal microvasculature, altering renal hemodynamics and the response of the renal vascular bed to changes in renal perfusion pressure (RPP) in female mice. Using Doppler ultrasonography, we found that resistive index and pulsatility index were elevated in young Eln+/− and aged mice. Histological examination showed thinner internal and external elastic laminae, accompanied by increased elastin fragmentation in the medial layer without any calcium deposits in the small intrarenal arteries of kidneys from young Eln+/− and aged mice. Pressure myography of interlobar arteries showed that vessels from young Eln+/− and aged mice had a slight decrease in distensibility during pressure loading but a substantial decline in vascular recoil efficiency upon pressure unloading. To examine whether structural changes in the renal microvasculature influenced renal hemodynamics, we clamped neurohumoral input and increased renal perfusion pressure by simultaneously occluding the superior mesenteric and celiac arteries. Increased renal perfusion pressure caused robust changes in blood pressure in all groups; however, changes in renal vascular resistance and renal blood flow (RBF) were blunted in young Eln+/− and aged mice, accompanied by decreased autoregulatory index, indicating greater impairment of renal autoregulation. Finally, increased pulse pressure in aged Eln+/− mice positively correlated with high renal blood flow. Together, our data show that the loss of elastin negatively affects the structural and functional integrity of the renal microvasculature, ultimately worsening age-related decline in kidney function.
Regulation of Nicotiana benthamiana cell death induced by citrus chlorotic dwarf-associated virus-RepA protein by WRKY 1
Authors: Qin Yangyang , Zhao Jinfa , Wang Jiajun , Ye Xiao , Zhou Changyong , Zhou Yan
Published: April 2023

Citrus chlorotic dwarf-associated virus (CCDaV) is a Citlodavirus species in the Geminiviridae family that causes tremendous economic loss to the citrus industry in China. Some proteins encoded by geminiviruses are crucial for the interaction between the virus and its host plant. However, the exact functions of CCDaV-encoded proteins such as CCDaV-RepA have not been investigated. This study presents evidence that CCDaV-RepA elicits a hypersensitive response (HR)-like cell death in Nicotiana benthamiana that was accompanied by the production of H2O2 and ion leakage, which suggested that CCDaV-RepA is a potential recognition target for inducing host defense responses. Furthermore, the rolling-circle replication motifs of CCDaV-RepA are associated with triggering HR-like cell death in N. benthamiana. Confocal microscopy and deletion mutagenesis assays showed that CCDaV-RepA was located in the nucleus, while the first eight amino acids (aa) at the N terminus and two regions located between aa residues 122-263 and 220-264 of RepA were not associated with nuclear localization. Tobacco rattle virus-induced gene silencing of the key signaling cascade components revealed that HR-like cell death induced by RepA was inhibited in WRKY1-silenced N. benthamiana. Moreover, WRKY1 expression was upregulated in RepA-GFP infiltrated Overall, the results suggest that NbWRKY1 positively regulated CCDaV-RepA -induced cell death in N. benthamiana. These findings provide novel information for further research on the interactions between CCDaV and the host plant.
Voice vs. silence: the role of cognitive appraisal of and emotional response to stressors
Authors: Pahng Phoebe Haemin , Kang Sung Mo
Published: April 2023

Stress is in the nature of work, employees, teams, and organizations. Some speak up under stress, whereas others keep silent. Given that employee voice has long been recognized to enhance high-quality decisions and organizational effectiveness, understanding conditions under which employees practice voice is important. In this article, we combine appraisal theory, prospect theory, and threat-rigidity thesis so as to enrich our understanding of the relationship between stressors and voice. In so doing, our theory paper integrates threat-rigidity thesis, prospect theory, and appraisal theory on the basis of the interaction between cognition and emotion, and it explores the detailed cognition-emotion-behavior (voice) relationship.
A systematic review evaluating loneliness assessment instruments in older adults
Authors: Bugallo-Carrera César , Dosil-Díaz Carlos , Anido-Rifón Luis , Pacheco-Lorenzo Moisés , Fernández-Iglesias Manuel J. , Gandoy-Crego Manuel
Published: April 2023

Introduction and objectives

The experiences and changes that come along with old age may lead to a feeling of loneliness, usually followed by negative physical and mental manifestations. In this systematic review, we evaluated the existing tools to assess loneliness in older adults.

Methods

We performed a literature search in the Web of Science, Medline, and PsycINFO, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After, we examined the psychometric properties of the instruments with a focus on reliability, validity, and main conclusions.

Results

We included 27 articles published between 1996 and 2021.

Conclusion

To date, there are few instruments to assess loneliness in older adults. In general, they present adequate psychometric properties, although it is true that some scales show somewhat low levels of reliability and validity.
Multidimensional schizotypy and embodied emotions
Authors: Torregrossa Lénie J. , Blain Scott D. , Snodgress Matthew A. , Park Sohee
Published: April 2023

Background

Disembodiment and socio-emotional deficits are core features of the schizophrenia spectrum from the prodromal stages to chronic illness. A recent study documented anomalous emotional embodiment in individuals with schizophrenia. Although bodily self disturbances have been shown to precede and predict psychosis onset in at-risk populations, the etiology of anomalous emotional embodiment remains largely unexplored. The present study investigated bodily maps of emotions in relation to schizotypy to extend our understanding of embodied emotions in the schizophrenia spectrum.

Methods

A total of 419 participants (312 female; 19.50 ± 1.22 years) completed a topographical body mapping task where they reported patterns of embodiment experienced in the context of eleven different emotions and a neutral state (EmBODY). Embodied emotions were investigated in relation to multidimensional schizotypy.

Results

Individuals with elevated negative schizotypy experienced embodied emotions with higher intensity (r = 0.16, p = 0.003) but lower clarity (i.e., endorsing activation and deactivation in the same bodily location; β = −0.28, 95% CI [−0.54, −0.03], Z = 2.25, p=0.02) and endorsed more incongruent bodily sensations of emotions (i.e., reporting bodily activation in the context of a low-arousal emotion, r = 0.12, p = 0.05; reporting bodily deactivation in the context of high-arousal emotions, r = 0.13, p = 0.02). In line with the anomalous emotional embodiment documented in individuals with schizophrenia, some of these differences were particularly notable for low-arousal emotions.

Discussion

These results reveal negative schizotypy as a significant correlate of differences in emotional embodiment. More work is needed to link these differences to the anomalous bodily sensations of emotions documented in schizophrenia and assess their functional impact.
Agomelatine's antiglycoxidative action—In vitro and in silico research and systematic literature review
Authors: Nesterowicz Miłosz , Lauko Kamil Klaudiusz , Żendzian-Piotrowska Małgorzata , Ładny Jerzy Robert , Zalewska Anna , Maciejczyk Mateusz
Published: April 2023

Introduction

Agomelatine is an atypical antidepressant drug enhancing norepinephrine and dopamine liberation; nevertheless, additional mechanisms are considered for the drug's pharmacological action. Since protein glycoxidation plays a crucial role in depression pathogenesis, agomelatine's impact on carbonyl/oxidative stress was the research purpose.

Methods

Reactive oxygen species scavenging (hydroxyl radical, hydrogen peroxide, and nitrogen oxide) and antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating assays) of agomelatine were marked. Agomelatine's antiglycoxidation properties were assayed in sugars (glucose, fructose, and galactose) and aldehydes- (glyoxal and methylglyoxal) glycated bovine serum albumin (BSA). Aminoguanidine and α-lipoic acid were used as standard glycation/oxidation inhibitors.

Results

Agomelatine did not show meaningful scavenging/antioxidant capacity vs. standards. Sugars/aldehydes increased glycation (↑kynurenine, ↑N-formylkynurenine, ↑dityrosine, ↑advanced glycation end products, and ↑β-amyloid) and oxidation (↑protein carbonyls and ↑advanced oxidation protein products) parameters in addition to BSA. Standards restored BSA baselines of glycation and oxidation markers, unlike agomelatine which sometimes even intensifies glycation above BSA + glycators levels. Molecular docking analysis of agomelatine in BSA demonstrated its very weak binding affinity.

Discussion

Agomelatine's very low affinity to the BSA could proclaim non-specific bonding and simplify attachment of glycation factors. Thereby, the drug may stimulate brain adaptation to carbonyl/oxidative stress as the systematic review indicates. Moreover, the drug's active metabolites could exert an antiglycoxidative effect.
Excellence fulfilled? On the unique developmental needs of professional athletes
Authors: Baker Joseph , Johnston Kathryn , Singh Harjiv , Farah Lou , Lablans Dale
Published: April 2023

While the term “athlete development” has been used to capture the changes (physical, psychological, etc.) that occur as an athlete moves from initial sport engagement to elite performance, much of the research in this area has focused on earlier stages of the pathway, with very little work examining the highest levels of sport. Considering a person's bio-psycho-social development continues through adulthood, the limited attention to development for athletes at higher competitive levels is perhaps surprising. In this short article, we highlight several notable discrepancies between different competitive levels (e.g., pre-professional sport and professional sport) in the way development is conceptualized, contextualized, and operationalized. We use available evidence to provide guidance for researchers and practitioners to encourage the delivery of structured developmental programming in professional sport systems to aid with the transitionary period between pre-elite and elite levels, and to help foster career longevity.