bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular detection and identification of hemotropic Mycoplasma species in dogs and their ectoparasites in Iran
Authors: Beus Kimia , Goudarztalejerdi Ali , Sazmand Alireza
Published: May 2023

Hemotropic Mycoplasma species are vector-borne bacteria that attach and grow on the surface of erythrocytes in various mammals, yet reports of canine hemoplasmosis in Iran are scarce. The aim of this study was molecular detection and identification of hemoplasmas in the blood of dogs (n = 370) from five provinces of Iran and ectoparasites infesting them including Ctenocephalides canis and Pulex irritans fleas, Rhipicephalus sanguineus sensu lato ticks, Heterodoxus spiniger lice and Hippobosca longipennis keds. The presence of hemotropic Mycoplasma spp. pathogens were detected using group-specific, and identified using species-specific conventional PCRs detecting Mycoplasma haemocanis (Mhc) and Candidatus Mycoplasma haematoparvum (CMhp) followed by Sanger sequencing. Correlation of infection and risk factors (geographical area, keeping condition, body condition, sex, age, infestation with ectoparasite) were analyzed. In total, 210 dogs (56.7%) tested PCR-positive for hemotropic Mycoplasma spp. Species-specific PCR and sequencing revealed infection with Mhc in 17.8%, with CMhp in 7.02% and co-infection in 31.9% of dogs. Flea infestation, poor body condition, and being older than 3-years-old correlated with hemoplasmosis. In ectoparasites, DNA of hemoplasmas were detected only in fleas i.e. Mhc in P. irritans, CMhp in P. irritans and C. canis, and co-infection with Mhc an CMhp in C. canis. To our knowledge, this is the first large-scale molecular epidemiology study of canine hemoplasmosis in Iran. Considering the high prevalence of canine hemoplasmosis all over the country including potentially zoonotic CMhp, effective ectoparasite control strategies, regular examination of dogs, successful chemoprophylaxis and public awareness strategies are advocated.
Sustainability and Environmental Impact of the Tourism Sector: Analysis Applied to Swimming Pools in the Hotel Industry on the Costa Brava
Authors: Arimany-Serrat Núria , Guillén Juan José Gómez
Published: May 2023

The hotel industry already has a high level of sensitivity to environmental sustainability at all levels, from the owners and managers of the establishments to the clients who stay there. The Costa Brava is an area with high water stress during the high tourist season; therefore, any initiative that seeks to make the sector and one of its main assets, such as swimming pools, more environmentally sustainable is of great social interest. Swimming pools are one of the hotel industry's most important assets in attracting visitors to their facilities. Improving the energy efficiency of these facilities will not only improve the sustainability of the hotel industry but will also improve operating costs and allow establishments to dedicate more resources to their hospitality business. The aim of this research is to collect data on the swimming pools installed in hotels on the Costa Brava, to calculate the carbon footprint equivalent to the consumption of electrical energy and to identify the possibilities for improvement in the installations
Nanoscale Doping of Polymeric Semiconductors with Confined Electrochemical Ion Implantation
Authors: Xiang Lanyi , He Zihan , Jia Lingxuan , Jiang Ziling , Dai Xiaojuan , Ma Yingqiao , Liu Liyao , Meng Qing , Zou Ye , Zhang Fengjiao , Zhu Daoben , Di Chong-an
Published: May 2023

Nano-resolved doping of polymeric semiconductors can overcome scaling limitations toward highly integrated flexible electronics, but remains a fundamental challenge. Here, we report a general methodology for achieving nanoscale ion-implantation-like electrochemical doping of polymeric semiconductors by confining counterion electromigration in an electrolyte. The process is mediated by adjusting the electrolyte glass transition temperature (Tg) and the operating temperature (T), which generates a highly localized electric field distribution and anisotropic ion migration that nearly vertical to the nanotip electrodes. The confined doping produces a record resolution of 56 nm with a lowest lateral diffusion length (LDL) down to 6 nm, which approaches the polaron delocalization limit of the host polymer. Moreover, we demonstrate a universal exponential dependence of the doping resolution on the temperature difference (Tg−T) that can be used to depict the doping resolution for almost infinite polymeric semiconductors. Our results may stimulate the design and nanofabrication of novel polymer devices based on the nanoscale defined doping patterns.
Attenuated Salmonella carrying siRNA-PD-L1 and radiation combinatorial therapy induces tumor regression on HCC through T cell-mediated immuno-enhancement
Authors: Jia Huijie , wei pengkun , Zhou Shijie , Hu Yuanyuan , Zhang Chunjing , Li Bingqian , Gan Zerui , Xia Yuanling , Jiang Hanyu , Shao Mingguang , Guo Sheng , Yang Zishan , Zhong Jiateng , Ren Feng , Zhang Huiyong , Zhang Yongxi , Zhao Tiesuo
Published: May 2023

Hepatocellular carcinoma (HCC), the most prevalent type of aggressive liver cancer, accounts for the majority of liver cancer diagnoses and fatalities. Despite recent advancements in HCC treatment, it remains one of the deadliest cancers. Radiation therapy (RT) is among the locoregional therapy modalities employed to treat unresectable or medically inoperable HCC. However, radio-resistance poses a significant challenge. It has been demonstrated that RT induced the upregulation of programmed death ligand 1 (PD-L1) on tumor cells, which may affect response to PD-1-based immunotherapy, providing a rationale for combining PD-1/PD-L1 inhibitors with radiation. Here, we utilized attenuated Salmonella as a carrier to explore whether attenuated Salmonella carrying siRNA-PD-L1 could effectively enhance the anti-tumor effect of radiotherapy on HCC-bearing mice. Our results showed that a combination of siRNA-PD-L1 and radiotherapy had a synergistic anti-tumor effect by inhibiting the expression of PD-L1 induced by radiation therapy. Mechanistic insights indicated that the combination treatment significantly suppressed tumor cell proliferation, promoted cell apoptosis, and stimulated immune cell infiltration and activation in tumor tissues. Additionally, the combination treatment increased the ratios of CD4+ T, CD8+ T, and NK cells from the spleen in tumor-bearing mice. This study presents a novel therapeutic strategy for HCC treatment, especially for patients with RT resistance.
Elucidation of Molecular Mechanisms of ASK1 Regulation by 14-3-3 for NASH therapeutics: Insights from Computational Simulations
Authors: Agrahari Ashish , Sarmadhikari Debapriyo , Asthana Shailendra
Published: May 2023

Nonalcoholic steatohepatitis (NASH) is a global health concern with no effective treatment options. Apoptosis-signaling kinase 1 (ASK1) hyperactivity induced by oxidative stress has been identified as a key contributor to hepatic inflammation, apoptosis, and liver fibrogenesis, is the hallmark of NASH. Several attempts by companies and academia have attempted to develop ASK1 inhibitors, however, they failed in clinical trials due to substantial side effects. Hence, there is an unmet need for an alternate approach such as protein-protein interactions (PPIs) to modulate ASK1 activity via allosteric regulators rather than complete blockage of ASK1. The PPI driven allosteric inhibition of ASK1 traverses a promising strategy as its regulators in disease states are well documented. Among them, 14-3-3, a -ve regulator that allosterically inhibits ASK1 as it restricts the access of the catalytic site by preventing the substrate from entering into the catalytic site, however the mechanistic insights have not been explored. The 14-3-3 binding site and its impact at catalysis site is wired through an unstructured region indicating the possibility that this process is highly dynamics coupled, a major bottleneck in PPI-based inhibitor designing. Therefore, we are investigating the structural behavior of 14-3-3 and ASK1 interfaces using molecular modeling and microsecond molecular dynamics simulations. We identified that dynamics which correlate the structural and functional implications of the allosteric modulation via 14-3-3 on ASK1’s catalytic site and underscores a novel strategy for allosteric inhibition of ASK1. Extensive molecular dynamics simulations revealed that the complex state of ASK1 (with 14-3-3) was more stable than the apo state with a more restricted catalytic pocket volume as it visualizes that it potentially prevents the substrate entry in the absence of a ligand. Our findings provide structural determinants of allosteric regulation of ASK1 by 14-3-3 for the development of novel therapeutics against ASK1.
Fasting-induced RNF152 re-sensitizes gallbladder cancer cells to gemcitabine by inhibiting mTORC1-mediated glycolysis
Authors: Tao Ying , Gong Zijun , Shen Sheng , Ding Yaqi , Zan Rui , Zheng Bohao , Sun Wentao , Ma Chaolin , Shu Mengxuan , Lu Xiao , Liu Han , Ni Xiaoling , Liu Houbao , Suo Tao
Published: May 2023

Accumulating evidence indicates that the lysosomal Ragulator complex is essential for the full activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal mTORC1 activation has been implicated in cancer and glycolytic metabolism associated with drug resistance. Fasting is known to upregulate the ring finger protein 152 (RNF152) and mediate the metabolic status of cells. Here we report that RNF152 regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator, and attenuates gemcitabine resistance in gallbladder cancer (GBC). The effects of RNF152 expression on molecular behavior were analyzed. RNF152 and p18 levels were detected in tissues, and detailed mechanistic studies were undertaken by using activators, inhibitors, and lentivirus transfections. RNF152 levels were significantly lower in GBC than in adjacent non-cancer tissues. Fasting impairs glycolysis, induces gemcitabine sensitivity, and upregulates the expression of RNF152. RNF152 overexpression increases the sensitivity of GBC cells to the chemotherapeutic drug gemcitabine, whereas silencing RNF152 exhibited the opposite effect. Our study verified that fasting-induced RNF152 ubiquitinates p18, resulting in proteasomal degradation. RNF152 deficiency induces the increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity, to promote glycolysis and decrease gemcitabine sensitivity in GBC. Our research suggests that RNF152 is a fasting sensor and an important regulator of the mTORC1 signal. RNF152 functions as a tumor suppressor that can suppress the activity of mTORC1 to inhibit glycolysis and enhance the sensitivity of gemcitabine in GBC. RNF152 may have potential in the therapeutic management of GBC.
The interaction between microbiome and epigenetic diversity as a source of phenotypic variation for fish with low genetic diversity
Authors: Anka Ishrat , Webster Tamsyn Uren , Berbel-Filho Waldir , Hitchings Matthew , Overland Benjamin , de Leaniz Carlos Garcia , Consuegra Sofia
Published: May 2023

Non-genetic sources of phenotypic variation, such as the epigenome and the microbiome, could be important sources of adaptive variation for species with low genetic diversity, but little is known about the complex interaction between them and the genetic diversity of the host, particularly in wild populations. We examined the skin microbiome composition of two closely related mangrove killifish species with different mating systems (self-fertilising and outcrossing) under sympatric and allopatric conditions, to partition the influence of the genotype and the environment on their microbiome and epigenetic profiles. The diversity and community composition of the skin microbiome were shaped by strong genotype by environment interactions. We also found positive relationships between individual genetic diversity (heterozygosity) and microbiome alpha diversity (Faith and Chao1 measures) and between epigenetic variation and alpha diversity (Simpson evenness). Individual pairwise epigenetic and microbiome differentiation were positively correlated and influenced by species. We propose that the interaction between the host genotype, the microbiome and the epigenome can provide a plastic response to environmental variation, particularly relevant for individuals with low genetic diversity, and highlight the importance of considering the holobiont as the unit of selection to understand adaptation to environmental change.
Malnutrition as a Prognostic Factor in the Survival of Patients With Gastric Cancer
Authors: Bicakli Derya Hopanci , Miftari Almir , Almuradova Elvina , Aktuna Atalay , Gursoy Pinar , Cakar Burcu , Ersin Sinan , Sanlı Ulus Ali , Goker Erdem
Published: May 2023

Objective The purpose of this study was to identify the effects of nutritional status and sarcopenia on survival in gastric cancer (GC) patients. Research Methods: This prospective study was conducted with 150 GC patients at the oncology outpatient clinic. Malnutrition and sarcopenia status were determined according to The Patient Generated Subjective Global Assessment (PG-SGA) and anthropometric measurements. Survival analyses were conducted using Kaplan–Meier method and Cox-regression analysis. Results The mean age was 60.1 ± 11.4, and 64% (n = 96) were male, 36% were female (n = 54) patients. Severe malnutrition was observed in 63.3% (n = 95) of patients. In univariate analysis, the mean survival time (ST) for patients with a PG-SGA score < 9 point was 76.3 ± 7.4 month (95% CI:61.7–90.9), for patients with PG-SGA score ≥ 9 was 35.8 ± 4.1 month (95% CI:27.8–43.7) (p < 0.001). The mean ST for patients with and without sarcopenia was 32.0 ± 7.3 month (95% CI:17.7–46.3), 54.1 ± 4.8 month (95% CI:44.7–63.6) respectively (p < 0.05). In multivariate analysis, the risk of death in the patients who didn’t undergo gastrectomy [HR = 1.9 (95% CI:1.2–2.9)], malnourished [HR = 2.3 (95% CI:1.5–3.5)], had metastases [HR = 2.4 (95% Cl:1.4-4.0)] was higher. With the adjustment there was no association between the survival and sarcopenia (p > 0,05). Conclusions Malnutrition was identified as one of the independent risk factors for survival in GC patients, similar to the presence of metastases and the absence of gastrectomy. GC patients should be followed carefully in terms of these issues and nutritional interventions should be made when necessary.
Periodontitis is associated with uncontrolled hypertension: results from a cross-sectional study of urban elderly population in southeast China
Authors: Chen Yue , Zheng Jiaoer , Zhu Haihua
Published: May 2023

Background Periodontitis is a common local inflammatory disease associated with hypertension, this study aims to explore the relationship between periodontitis and uncontrolled hypertension and whether inflammation indication is a mediator of this relationship.Methods 1488 elders attending annual physical and oral examinations in Zhejiang province were included in this study. The staging of Periodontitis was classified as none, mild-moderate and severe. Uncontrolled hypertension was categorized as: normotensive (SBP < 140 mmHg and DBP < 90 mmHg) and hypertensive (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). Peripheral blood samples were collected, information on hypertension history and potential confounders (age, gender, smoking, alcohol consumption, exercise frequency, diabetes) was collected in questionnaires. The correlation between periodontitis and hypertension was investigated using linear regression analyses, mediation analysis was assessed for the effect of inflammation on hypertension.Results The results showed that uncontrolled hypertension is statistically significant associated with periodontitis, the association is mediated by inflammation indexes.Conclusions In a study of urban elderly population in southeast China, periodontitis is found to be significantly associated with uncontrolled hypertension, such relation is mediated by WBC and neutrophil count. Promotion of periodontal health strategies in the dental setting could help reduce the burden of hypertension and its complications.
Salivary pellicle modulates biofilm formation on titanium surfaces
Authors: Martínez-Hernández Miryam , Reyes-Grajeda Juan Pablo , Hannig Matthias , Almaguer-Flores Argelia
Published: May 2023

Objectives.
The present study aimed to evaluate the potential of the salivary pellicle (SP) formed on titanium (Ti) surfaces to modulate the formation of a biofilm composed of Streptococcus gordonii, Actinomyces naeslundii, Fusobacterium nucleatum, and Porphyromonas gingivalis.
Materials and Methods.
Ti substrates were incubated for two hours with a pool of saliva samples obtained from 10 systemically and periodontally healthy subjects. Enamel substrates were included as a biological reference. Scanning electron microscopy (SEM) and Raman spectroscopy analysis were used to analyze the formation of the salivary pellicle. After the SP formation, the surfaces were incubated for 12 hours with a mix of Streptococcus gordonii, Actinomyces naeslundii, Fusobacterium nucleatum, and Porphyromonas gingivalis. The number of bacterial cells attached to each surface was determined by the XTT assay, while bacterial viability was analyzed by fluorescence microscopy using the LIVE/DEAD® BacLightTM kit.
Results.
The SEM and Raman spectroscopy analysis confirmed the presence of a salivary pellicle formed on tested surfaces. Regarding the biofilm formation, the presence of the SP decreases the number of the bacterial cells detected in the test surfaces, compared with the uncover substrates. Even more, the SP-covered substrates showed similar bacterial counts in both Ti and enamel surfaces, meaning that the physicochemical differences of the substrates were less determinant than the presence of the SP. While on the SP-uncover substrates, differences in the bacterial adhesion patterns were directly related to the physicochemical nature of the substrates.
Conclusions.
The salivary pellicle was the main modulator in the development of the biofilm consisting of representative oral bacteria on the Ti substrates.
Clinical relevance:
The results of this study provide valuable information on the modulatory effect of the salivary pellicle on biofilm formation; such information allows us to understand better the events involved in the formation of oral biofilms on Ti dental implants.
Practical Strategies to Achieve Resilient Health Systems: Results from a Scoping Review
Authors: Bishai David , Saleh Basma , Huda Maryam , Aly Eman Mohammed , Hafiz Marwa , Ardalan Ali , Mataria Awad
Published: May 2023

Background: This paper presents the results of a systematic review to identify practical strategies to create the institutions, skills, values, and norms that will improve health systems resilience.
Methods: A PRISMA 2020 compliant systematic review identified peer-reviewed and gray literature on practical strategies to make health systems more resilient. Investigators screened 970 papers to identify 65 English language papers published since 2015.
Results: Practical strategies focus efforts on system changes to improve a health system’s resilience components of collective knowing, collective thinking, and collaborative doing. The most helpful studies identified potential lead organizations to serve as the stewards of resilience improvement, and these were commonly in national and local departments of public health. Papers on practical strategies suggested possible measurement tools to benchmark resilience components in efforts to focus performance improvement and ways to sustain their use. Essential Public Health Function (EPHF) measurement and improvement tools are well-aligned to the resilience agenda. The field of health systems resilience lacks empirical trials linking resilience improvement interventions to outcomes.
Conclusions: The rigorous assessment of practical strategies to improve resilience based on cycles of measurement should be a high priority.
Structural equation model of the relationship between depression with functional and nutritional status among Iranian older women: A Cross-sectional Study
Authors: Rezapour Vahideh , Papi Shahab , Matlabi Hossein , Tanjani Parisa Taheri
Published: May 2023

Background
In this study we used the structural equation model (SEM) and confirmatory factor analysis (CFA) to evaluate the relationship between the activities of daily living instrumental activities of daily living, and mini nutritional assessment with depression.
Methods
In this research, using a systematic random sampling method, 384 older women were selected from people covered by the health centers in Marand, Iran. To collect data, we used several tools, including Demographic Information Questionnaire, GDS, MNA, ADL, and IADL. The Statistical Package for the Social Sciences (SPSS) software version 28 was used for descriptive statistics and drawing figures, and AMOS software version 26 was used to analyze data. A P-value < 0.05 was considered as significant.
Results
According to the results, the obtained model had a good fit (P < 0.05, RMSEA = 0.071, CFI = 0.965, GFI = 0.934, IFI = 0.937, RFI = 0.918, χ^2/df = 1.46). Based on the CFA results, the MNA, IADL, and ADL constructs had an inverse and significant effect on the depression of the older people In addition, the IADL score had the highest effect on the depression of the elderly (P = 0.03), followed by ADL (P = 0.034) and MNA (P < 0.0013).
Conclusion
According to our results, functional disability and malnutrition are related to the risk of depression in older people.
Endogenous bile acids are associated with body lipid accumulation in non-diet induced obese pigs
Authors: Hu Yaolian , Wu Aimin , Yan Hui , Pu Junning , Luo Junqiu , Zheng Ping , Luo Yuheng , Yu Jie , He Jun , Yu Bing , Chen Daiwen
Published: May 2023

Background
Non-diet-induced obesity has been difficult to improve due to the complex etiology. Pigs can serve as an animal model for biomedical researches due to their physiological similarities to humans. This study first explored the differences in endogenous bile acids profiles (content and composition) between lean and obese pigs when they were fed to the same diet. Then, the effects of the characteristic bile acids within obese pigs on lipid accumulation were further verified by using 3T3-L1 adipocyte cells model.
Methods
Fourteen pigs including lean and obese pigs with body weight about 80 kg were fed the same diet with a level of feeding at approximately 3% of their respective body weight daily for 42d. The 3T3-L1 pre-adipocytes were cultured in a medium with high glucose levels, and then differentiated into mature adipocytes using differentiation medium.
Results
There was a significant difference in endogenous bile acids profiles between obese and lean pigs. The obesity had a strong correlation with isoallolithocholic acid and 3-oxodeoxycholic acid in colonic digesta of pigs, and isoallolithocholic acid enhanced lipid content in 3T3-L1 adipocytes. The differential bile acids between obese and lean pigs may be caused by the differences in gut microorganisms.
Conclusion
The results provide evidences that the obesity of obese pigs is independent of dietary nutrients intake, but closely related to endogenous bile acids, implying that bile acids may be the targets to prevent non-diet-induced obesity.
Profound sex-specific differences of metabolic hormone and adipose tissue dynamics induced by moderate low-carbohydrate and ketogenic diet
Authors: Smolensky Ilya , Zajac-Bakri Kilian , Odermatt Timothy Sasha , Brégère Catherine , Cryan John F. , Guzman Raphael , Timper Katharina , Inta Dragos
Published: May 2023

Low-carbohydrates diets are increasingly used to treat obesity and metabolic disorders. A very low-carbohydrate, ketogenic diet is hard to follow and is linked to severe side effects. Therefore, a less restrictive unsaturated fat-based low-carbohydrate diet seems a promising alternative. Since neither sex differences, nor their effect on specific adipose tissue compartments have been investigated thoroughly in these diets, we aimed to analyze their dynamics and metabolic factors in mice. We found a significant sexual dimorphism with decreased body weight and subcutaneous fat only in males on ketogenic diet, while diminished insulin, elevated ghrelin and FGF-21 were present with a differential time course in both sexes. The non-ketogenic low-carbohydrate diet increased body weight and visceral fat in females, but induced leptin elevation in males. Both diets induced transient TNFɑ increase only in males and had no impact on behavior. Altogether, these results reveal complex sex-dependent effect of dietary interventions, indicating unexpectedly females as more prone to unfavorable metabolic effects of low-carbohydrate diets.
Research on the Appearance Size Detection Method of Highway Engineering Based on Tilt Photography Technology
Authors: Wang Fang , Liu Shixiao , Zhang Huiying , Huang Siping
Published: May 2023

Based on the application research of UAV tilt photogrammetry technology in highway engineering design and construction compliance detection, this paper changes the shortcomings of traditional detection with low efficiency, poor overall evaluation level and high cost, and provides a new high-efficiency, high-precision and low-cost highway engineering design and construction compliance evaluation and detection method for design units. After constructing the inclined real scene model for the aerial photography of the test section of Uma expressway, the new LSV drawing software is used to integrate the three-dimensional real scene model with the design CAD drawing, extract and measure the virtual 3M ruler measurement method, EPS conversion two-dimensional model, and extract and measure the appearance storage quality inspection index in the standard for quality inspection and evaluation of Highway Engineering - Civil Engineering (JTGF80/1-2017). The advantages of the new system are verified by comparing with the traditional compliance detection in terms of index coverage, detection accuracy and cost. It provides a reference for the further study of highway engineering design compliance evaluation in the later stage.
Identification Of Platelet-related Biomarkers And Construction of Transcriptional Regulatory Network in Patients with Proliferative Diabetic Retinopathy
Authors: Lu Mingzhi , Jiao Feng , Lu Xiulan , Huang Rong , Yang Wanju , Ren He , Xing YiQiao
Published: May 2023

Objective: To identify the platelet-related biomarkers in Proliferative diabetic retinopathy (PDR).
Methods: Two mRNA expression profiles of PDR (GSE102485 and GSE60436) were downloaded from the Gene Expression Omnibus (GEO) database with the platelet-related genes from gene set enrichment analysis (GSEA) database. A protein-protein interaction (PPI) network was established to screen out hub genes based on the interaction between differentially expressed platelet-related genes (DEPRGs), followed by the prediction of the associated microRNAs (miRNAs), transcription factors (TFs) and drugs, which were taken to establish the regulatory networks of miRNA-hub gene, TF-hub gene and drug-hub gene. To verify the expression of Hub genes, both retinal samples from experimental diabetes mouse models and human retina microvascular endothelial cells (HRMECs) treated with high glucose (HG) were subjected to quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).
Results: A total of 168 DEPRGs were determined, with 146 genes for upregulation and 22 for downregulation. 9 hub genes (CDC42, GNAI2, LCK, LCP2, LYN, PLCG2, PTPN6, RAC1 and SYK) were eventually screened. 446 miRNAs, 46 TFs and 138 hub gene targeted by drugs were presented after prediction. RAC1 and GNAI2 respectively targeted by 156 miRNAs and 19 TFs lied the most connected hub genes in the miRNA-hub gene and TF-hub gene regulatory networks. Based on the drug-hub gene regulatory network, LCK was targeted by 52 drugs. qRT-PCR results indicated that the expression of LPC2 and PTPN6 was upregulated in both diabetes mouse models and HRMECs treated with HG.
Conclusions: Nine hub genes were screened with the prediction of miRNAs, which were targeted by TFs and drugs, and may play an essential role in the progression of PDR, utilized as potential biomarkers and therapeutic targets.
Structural analysis and susceptibility inversion based on ground magnetic data to map the chromite mineral resources: A case study of the Koh Safi Chromite Ore Deposit, Parwan, Afghanistan
Authors: Rezayee Mohammad Hakim , Khalaj Mahdi , Mizunaga Hideki
Published: May 2023

The Koh Safi Chromite Ore Deposit is located in Afghanistan's northern-northeastern end of the Kabul-Kandahar ophiolite zone. Sedimentary formations, delayed volcanic, and ultramafic rock groups, including peridotites and serpentinites, could all have been found in the Koh Safi area, where structural discontinuities with the two trends of northwest-southeast and east-west can be identified. High-grade serpentinite units have many chromite deposits, whereas peridotite has a lot of medium-grade deposits. This paper performs a ground magnetic data analysis based on structural analysis and 3-D susceptibility inversion. The boundaries of structural faults and anomalous bodies are likely delineated in a northwest-to-southeast orientation using a series of derivative maps, including Total Horizontal Derivative, Analytical Signal, and Theta Map. For inversion, many regularization norms that included the range of smooth, intermediate, and compact models were used to examine a particular susceptibility value that occurred in a model cell. The sparse and blocky norms [0,1,1,1] were suggested for our inversion in field data based on synthetic data to determine an appropriate norm. A 3-D inversion of ground magnetic data shows that the highly magnetic zone supposed to be the host rocks seems to be where chromite occurs in the study area.
Tolerability of pulse high dose L-AmB as pre-emptive therapy in patients at high risk for intra- abdominal candidiasis: a phase 2 study (LAMBDA Study)
Authors: Rinaldi Matteo , Bartoletti Michele , Bonazzetti Cecilia , Caroccia Natascia , Gatti Milo , Tazza Beatrice , Horna Clara Solera , Giannella Maddalena , Viale Pierluigi
Published: May 2023

Background.
Intra-abdominal candidiasis (IAC) is burdened by high mortality rates. However, the correct management of a critically ill patient with suspected IAC is an issue still on debate. The aim of our study was to evaluate the safety of pulse high-dose of liposomal amphotericin B (L-AmB) in patients with suspected IAC managed with a Beta-D-Glucan (BDG)-guided strategy.
Methods.
Phase 2 prospective study enrolling adult patients with intra-abdominal sepsis following surgery. Patients received a single dose of L-AmB 5mg/kg on day 1. At day 3, L-AmB was discontinued in case of negativity of basal serum (1, 3)-Beta-D-Glucan (BDG) and was continued (3 mg/kg/daily) in case of positive basal BDG, or microbiologically confirmed IAC. The main endpoint was occurrence of adverse events according with common toxic criteria definition.
Results.
Overall, 40 patients were enrolled from January 2019 until August 2022. Of them 15 (37.5%) were male, median age was 65 (49–76) years. Urgent surgery accounted for 31 (77.5%) cases, principal indication was secondary/tertiary peritonitis (22, 55%), half of patients had a previous surgical operation within 30 days. Five (12.5%) patients had criteria for septic shock at enrolment. The median APACHE II score at ICU admission was 12 (10–15). In 33 (85%) cases IAC was excluded, whereas 5 (12.5%) and 2 (5%) patients had a probable and proven IAC, respectively. The single dose of L-AmB 5 mg/Kg was well tolerated in all patients, no early and late severe adverse events related to the drug were reported. L-AmB was discontinued in 65% of patients following a negative basal BDG result. All-cause 30-day mortality rate was 15%, in none case death was related to L-AmB administration or uncontrolled IAC. More specifically, mortality rates between patients with and without proven IAC was 0% vs. 15.8%, p = 0.99.
Conclusions.
The rate of proven IAC among critically ill high-risk patients was low, attesting at 5%. A single dose of L-AmB 5 mg/Kg following prompt withdrawal in case of basal negative BDG result seems to be a safe and effective approach in such population.
Evaluating Professionalism in Residency Training: The Learning Environment for Professionalism Survey
Authors: Byszewski Anna , Pearson Alexander , Wood Timothy , Lochnan Heather , Johnston Donna , Whiting Sharon
Published: May 2023

Background Professionalism is a key competency in multiple medical education frameworks. The teaching and evaluation of professionalism is an accreditation standard for undergraduate and postgraduate medical training in Canada. As a result, there is a need for valid tools to assess professionalism in the learning environment (LE). One method that has demonstrated promise is the Learning Environment for Professionalism (LEP) survey. It is a brief and balanced tool consisting of 11 questions that assesses medical trainees' and attending physicians' positive and negative professionalism behaviours. Previous studies have shown it is an easily administered, reliable tool that produces valid results for assessing professionalism in both undergraduate and postgraduate LEs. This study aimed to expand the application of the LEP survey to more varied programs, across several institutions and to examine LEs longitudinally over a longer period of time.Methods All postgraduate medical programs at the University of Ottawa were approached to participate in this study. Seven training programs (anesthesiology, cardiac surgery, plastic surgery, urology, family medicine, internal medicine, and pediatrics) agreed to facilitate the administration of the LEP survey at four hospitals in Ottawa (The Ottawa Hospital Civic and General campuses, the Ottawa Heart Institute, and Children’s Hospital of Eastern Ontario). The LEP survey was carried out iteratively between 2013 and 2020. The LE ratings in each training program and hospital were assessed longitudinally using univariate linear regression. A Bonferroni corrected p-value of ≤ .0045 was used to account for multiple comparisons.Results 3783 survey responses over seven years were included in the analysis. Overall, positive professional behaviours were observed across time and programs. However, one negative item relating to attending physicians treating patients unfairly because of their financial status, ethnic background, sexual or religious preferences worsened.Conclusions This study demonstrated that applying the LEP survey longitudinally across diverse training programs is feasible. Furthermore, it can help program leaders identify areas that require attention and acknowledge areas of exemplary professionalism. Implementation of the LEP survey is an effective strategy to demonstrate continuous monitoring of the LE to accrediting bodies and can be considered an important quality improvement metric.
The potential biomass resources for a sustainable bioenergy planning in West Africa: insight from Niger
Authors: Mounkaila Hama Amadou , Soulé Moussa , Cecilia Eberechi Osuagwu
Published: May 2023

Sub-Sahara Africa main energy supply comes from forest and coal mining. Indeed, wood is largely the most energy source that has been using in Niger, leading several environmental and climate impact. Consequence of the limited power Supply; and the weak alternative for upgrading existing energy production resources and technologies. This study aimed at: estimating the biomass resources, characterizing Niger bioenergy technologies and, assessing the potential sustainable biopower capacity. The method had involved a literature review, a survey; processing of spatial data (Land Use Land Cover, Plant Dry Matter, GIS. The results shown, a significant potential of biomass deposits of which respectively 651,788,458 tons/Ha/year, 6,935,764 tons/year, 20,876,240 tons/year, and 322,784,07 tons/year for forest resources, agricultural residues, livestock dung, and organic MSW. These resources should produce am significant sustainable bioenergy power and, resolve many conservation challenges. Therefore, deep investigations in the designing program, projects are important for sustainable perspectives regarding green bioenergy resources. And energy policy strategies must be developed, adapted promoted in order to help sustainable bioenergy well integration especially in rural area, despite all the potential barriers.
Receiver operating characteristic (ROC) to determine cut-off points of clinical and biomolecular markers to discriminate mortality in severe COVID-19 living at high altitude
Authors: Vélez-Páez Jorge Luis , Baldeón-Rojas Lucy , Herrera Cristina Cañadas , Montalvo Mario Patricio , Jara Fernando Esteban , Aguayo-Moscoso Santiago , Tercero-Martínez Wendy , Saltos Lenin , Jiménez-Alulima Glenda , Guerrero Verónica , Pérez-Galarza Jorge
Published: May 2023

Background
In 2020, Ecuador had one of the highest death rates because of COVID-19. The role of clinical and biomolecular markers in COVID disease prognosis, is still not well supported by available data. In order for these markers to have practical application in clinical decision-making regarding patient treatment and prognosis, it is necessary to know an optimal cut-off point, taking into consideration ethnic differences and geographic conditions.
Aim: To determine the value of clinical and biomolecular markers, to predict mortality of patients with severe COVID-19 living at high altitude.
Methods: In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of ROC, sensitivity, specificity and likelihood ratios were calculated to determine levels of clinical and biomolecular markers that best differentiate survivors versus non-survivors in severe COVID subjects that live at a high altitude setting.
Results: Selected cut-off values for ferritin (≥ 1225 ng/dl, p = 0.026), IL-6 (≥ 11 pg/ml, p = 0.005) and NLR (≥ 22, p = 0.008) at 24 hours, as well as PaFiO2 (≤ 164 mmHg, p = 0.015), NLR (≥ 16, p = p = 0.013) and SOFA (≥ 6, p = 0.031) at 72 hours, appear to have good discriminating power to differentiate survivors versus non-survivors. Additionally, odds ratios for ferritin (OR = 3.38); IL-6 (OR = 17.07); PaFiO2 (OR = 4.61); NLR 24h (OR = 4.95); NLR 72h (OR = 4.46), and SOFA (OR = 3.77) indicate increased risk of mortality when cut-off points were taken into consideration.
Conclusions: We proposed a straightforward and understandable method to identify dichotomized levels of clinical and biomolecular markers that can discriminate between survivors and non-survivors patients with severe COVID-19 living at high altitudes.
Catheter-related bloodstream infection caused by Tsukamurella tyrosinosolvens identified by secA1 sequencing in an immunocompromised child: a case report
Authors: Mizuno Shinsuke , Tsukamura Yoshiyuki , Nishio Shuro , Ishida Toshiaki , Hasegawa Daiichiro , Kosaka Yoshiyuki , Ooka Tadasuke , Nishi Junichiro , Kasai Masashi
Published: May 2023

Background: Tsukamurellaspp. are obligate aerobic, gram-positive, non-motile, and slightly acid-fast bacilli belonging to the Actinomycetes family. Theyshare many characteristics with Nocardia, Rhodococcus, Gordonia, and the rapidly growing Mycobacterium species. Therefore, standard testing may misidentify Tsukamurella spp. as another species. Accurate and rapid diagnosis is critical for proper infection management, but identification of this bacterium is difficult in the standard laboratory setting.
Case presentation: A bloodstream infection caused by a gram-positive bacterium and related to a central venous catheter was identified in an immunocompromised 2-year-old girl. Tsukamurella tyrosinosolvens was identified by modified secA1 sequencing. Antibiotic treatment and removal of the central venous catheter resolved the infection. Inappropriate management of the catheter during an overnight stay outside of the hospital was considered as a possible source of infection.
Conclusions: SecA1 sequencing may be a useful diagnostic tool in the identification of T. tyrosinosolvens. Providing proper central venous catheter care instructions to patients, their families, and medical staff is important for infection prevention.
Seasonal variation in the metabolome expression of Jania rubens (Rhodophyta) reveals eicosapentaenoic acid as a potential anticancer metabolite
Authors: Krupnik Nimrod , Israel Alvaro , Meiri David
Published: May 2023

Seaweeds of the intertidal zone are subjected to diverse stresses due to environmental changes in radiation, salinity, water quality, herbivore communities, etc. Thus, marine seaweeds developed various unique compounds to deal with environmental fluctuations. Therefore, they are a good source of unique novel compounds. Here, we explored the seasonal metabolomics changes in J. rubens and found notable changes between extracts of different seasons in the metabolomic profile and in their anticancer activity. The most bioactive extract was from samples collected during the Fall season, which demonstrated an LC50 of 178.39 µg/ml toward Non-Small Cell Lung Cancer (NSCLC), followed by the Winter season extract. The Fall and Winter extracts also displayed more resemblance in their metabolic profile relative to Spring and Summer extracts. The Fall extract was fractionated and tested for cytotoxic activity toward an array of cancer cell lines. Through a series of fractionations followed by a bio-guided assay, we isolated and identified the essential fatty acid, eicosapentaenoic acid, as the active anticancer agent, showing an LC50 of 5.23 µg · ml− 1 toward NSCLC. Our results emphasize the potential use of J. rubens as a source of beneficial fatty acids and stress the importance of environmental effects on metabolic constitutes.
The effect of lemborexant on insomnia in patients with psychiatric disorders: detailed evaluation using the Athens Insomnia Scale
Authors: Murayama Tomonori , Ito Yuji , Narita Kenji , Ishida Tetsuro , Hinotsu Shiro , Fujita Masahiko
Published: May 2023

Chronic insomnia is common and associated with reduced quality of life. Benzodiazepine hypnotics are commonly prescribed for insomnia, but have potential side effects including concentration impairment, somnolence, and dependence. Lemborexant is an orexin receptor antagonist considered to have fewer side effects. The objectives of this study were to evaluate in detail the effects of lemborexant and examine whether the addition of lemborexant could gradually taper off benzodiazepine hypnotics. We retrospectively examined the effectiveness of lemborexant in 28 outpatients with insomnia. Insomnia symptoms were assessed using the Athens Insomnia Scale before and after lemborexant administration. We also attempted to taper and assessed doses of benzodiazepine hypnotics using diazepam equivalents for some patients taking benzodiazepine hypnotics. The mean Athens Insomnia Scale score was significantly improved after lemborexant treatment (8.7 ± 5.2 vs. 3.8 ± 3.3; p < 0.01). Among the Athens Insomnia Scale sub-items, significant improvement was observed for six items: sleep induction, awakenings during the night, total sleep duration, sleep quality, well-being, functioning capacity, and sleepiness during the day. The mean benzodiazepine dose was significantly lower after lemborexant treatment (4.6 ± 5.0 mg vs. 2.1 ± 3.3 mg; p < 0.01). This study indicated the potential of lemborexant for improving insomnia and reducing benzodiazepine dose.
Spatio-temporal analysis of Highly Pathogenic Avian Influenza HPAI (H5N1) in poultry in Menofia governorate, Egypt
Authors: Elsobky Yumna , Eltholth Mahmoud , Abdalla Ehsan , Eissa Nourhan , Hadad Ghada , Nayel Mohamed , Salama Akram , Mousa Walid , Kamal Ahmed , Elkamshishi Mohamed
Published: May 2023

Background: Menofia governorate is one of Lower Egypt's governorates where the probability of zoonotic transmission of the H5N1 pandemic was high. This study aimed to investigate the spatiotemporal pattern, identify, and trace the highest risk clusters of HPAI H5N1 outbreaks at the subdistrict/village level in Menofia governorate, from 2006 to 2017 as a trial for tracking the HPAI H5N1 endemicity dynamics for better establishment of effective disease control strategies at that level.
Results: The epidemic curve in Menofia was similar to the national curve. Although the poultry population in Menofia was affected earlier than other places, the 1st Epidemic Wave (EW) started one week after the initial outbreak in Egypt, the HPAI H5N1 outbreaks never initiated from Menofia in all EWs. The outbreaks' spatial risk increases at the northern governorate border with a decrease in the spatial risk by the 6th EW. The hot spot region in Menofia was found in rural districts, especially villages, while outbreak density decreased with increased urbanization. Observed smoothed densities describe epidemic spread dynamics where the infection spreads and connects many different locations inside the same city, before jumping to new areas and directly connecting the nearest neighbor cities. The primary clusters could be predicted since they occur in the same areas where the highest relative risk clusters were recorded in the previous wave. Identifying continuous pinpointing clusters that persist for a long time, possibly spanning months, indicates the local transmission of the virus among poultry due to contact and widespread circulation. It is crucial to take early measures to prevent outbreaks at the initial sites before the outbreak acceleration phase, in order to minimize the geographic spread and confine the infection to specific areas. That suggests the need for the establishment of effective disease control strategies at the subdistrict level based on a better understanding of the endemicity dynamics.
Fine-scale clonal structure of the lingonberry Vaccinium vitis-idaea under the nurse plant Pinus pumila vegetation in alpine region, Mt. Norikura.
Authors: Sugimoto Kensuke , Kawai Rio , Koizumi Takahiko , Matsuo Ayumi , Suyama Yoshihisa , MIZUKI INOUE
Published: May 2023

Nursery effect is a positive interaction wherein a nurse plant improves the abiotic environment for another species (beneficiary plant) and facilitates its establishment. The evergreen shrub Vaccinium vitis-idaea (beneficiary plant) grows mainly under the dwarf shrub Pinus pumila (nurse plant) in the alpine regions of central Japan. However, whether V. vitis-idaea shrubs under various P. pumila shrubs spread through clonal growth and/or seeds remains unclear. Here, we aimed to investigate the clonal structure of V. vitis-idaea under the nurse plant, P. pumila, in Japanese alpine regions. MIG-seq analysis was conducted to compare isolated and patchy P. pumila plots on the ridge (PATs) and plots covered by dense P. pumila on the slope (MAT) on Mt. Norikura, Japan. We detected 15 and 17 multi-locus genotypes in 209 ramets across 11 PATs and 130 ramets in one MAT, respectively. Approximately half of the PATs consisted of a single genet. These results suggest that the seeds of V. vitis-idaea were dispersed under small P. pumila patchy shrubs and spread by clonal growth in small PATs. The genet abundance curve of MAT was more moderate than that of PATs, and the clonal diversity of MAT was lower than that of PATs on a small scale. Therefore, spatial spread of the nurse plant P. pumila facilitates germination via the seeds of V. vitis-idaea. Our results show that the nursery effect on the genetic diversity of beneficiary plant increased positively with the spatial size of nurse plants in alpine regions, leading the sustainability of the beneficiary populations.