bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary embolism and 529 human blood metabolites: genetic correlation and two-sample Mendelian randomization study
Authors: Feng Ruoyang , Lu Mengnan , Xu Jiawen , Zhang Feng , Yang Mingyi , Luo Pan , Xu Ke , Xu Peng
Published: August 2022

Background

The incidence of pulmonary embolism complications in the literature ranges from 10 to 50%, with a 0.5–10% risk of fatal pulmonary embolism. However, the biological cause of pulmonary embolism is unknown.

Methods

This study used data from the Genome-Wide Association Study (GWAS) of Pulmonary Embolism and Human Blood Metabolites from the UK Biobank, and the data from subjects of European ancestry were analyzed. We explored the relationship between pulmonary embolism and blood metabolites in three ways. We first analyzed the genetic correlation between pulmonary embolism and human blood metabolites using the linkage disequilibrium score regression (LDSC) and then analyzed the causal relationship between pulmonary embolism and meaningful blood metabolites obtained from the LDSC, a procedure for which we used Mendelian randomization analysis. Finally, we obtained transcriptome sequencing data for patients with a pulmonary embolism from the GEO database, analyzed differentially expressed genes (DEGs) in patients with pulmonary embolism versus healthy populations, and compared the DEGs with the resulting blood metabolite genes to further validate the relationship between pulmonary embolism and blood metabolites.

Result

We found six human blood metabolites genetically associated with pulmonary embolism, stearic acid glycerol phosphate ethanolamine (correlation coefficient = 0.2582, P = 0.0493), hydroxytryptophan (correlation coefficient = 0.2894, P = 0.0435), and N1-methyladenosine (correlation coefficient = 0.0439, P = 0.3728), and a significant causal relationship was discovered between hydroxytryptophan and pulmonary embolism. After screening microarray data from the GEO database, we performed differential gene analysis on the GSE19151 dataset and screened a total of 22,216 genes with P values less than 0.05, including 17,361 upregulated genes and 4854 downregulated genes. By comparing the resulting differentially expressed genes with six genes encoding blood metabolites, LIPC and NAT2 were found to be differentially expressed in association with pulmonary embolism.
MiR-659-3p inhibits osteosarcoma progression and metastasis by inhibiting cell proliferation and invasion via targeting SRPK1
Authors: Gong Yubao , Wei Zheng-Ren
Published: August 2022

Objective

Osteosarcoma is the most common primary bone cancer that affects mostly children and young adults. Despite the advances in osteosarcoma treatment, the long-term survival rate of metastatic patients has not significantly improved in the past few decades, thus demonstrating the need for novel therapeutic targets or methods to improve metastatic osteosarcoma treatment. In this study we aimed to elucidate the role of miR-659-3p and SRPK1 in osteosarcoma.

Methods

We evaluated miR-659-3p and SRPK1 function in osteosarcoma cell proliferation, migration, and cell cycle progression in vitro by using gain- and loss-of-function strategies. The effect of miR-659-3p in tumor progression and metastasis was determined by in vivo mouse model.

Results

We revealed that expression of miR-659-3p was significantly downregulated in osteosarcoma compared with normal bone cells and was inversely correlated with serine-arginine protein kinase 1 (SRPK1) expression. We proved that miR-659-3p targets 3’ UTR of SRPK1 and negatively regulates SRPK1 expression in osteosarcoma cells via luciferase assay. In vitro studies revealed that gain of miR-659-3p function inhibited osteosarcoma cells growth, migration, and invasion by down-regulating SRPK1 expression. Inversely, inhibiting miR-659-3p in osteosarcoma cells promoted cell growth, migration, and invasion. Cell cycle profile analysis revealed that miR-659-3p inhibited osteosarcoma cells’ G1/G0 phase exit by down-regulating SRPK1 expression. By using an in vivo mouse model, we demonstrated that miR-659-3p inhibits osteosarcoma tumor progression and lung metastasis by inhibiting SRPK1 expression and potentially downstream cell proliferation, and epithelial-to-mesenchymal transition genes.

Conclusions

This study demonstrated that miR-659-3p is a potential therapeutic method and SRPK1 is a potential therapeutic target for osteosarcoma treatment.
Evaluation of the diagnostic performance of colposcopy in the diagnosis of histologic cervical intraepithelial neoplasia 2+ (CIN2+)
Authors: Dorji Namkha , Tshering Sangay , Choden Sonam , Chhetri Meera , Bhujel Damanti , Wangden Tshering , Pradhan Birendra , Bhutia Pema Choden , Tshomo Ugyen
Published: August 2022

Background

Colposcopy is a tool for triaging screen positive women regardless of method used for cervical cancer screening. The objective of this study was to evaluate the diagnostic performance of colposcopy in the diagnosis of histologic cervical intraepithelial neoplasia 2+ (CIN 2+) at Jigme Dorji Wangchuck National Referral Hospital (JDWNRH), Thimphu, Bhutan.

Methods

This cross-sectional study was conducted from March 2021 to August 2021 among 299 women who availed colposcopy services at the colposcopy clinic of JDWNRH, Bhutan. Women included in this study were either screen positive (Pap smear) or were suspected to have invasive cancer; they underwent colposcopy and a cervical biopsy irrespective of colposcopy impression. This histopathologic assessment was considered as the gold standard test for the diagnosis of cervical intraepithelial neoplasia (CIN) or invasive cancer.

Results

The mean age of the study participants was 43 years (ranges, 25–76 years). The sensitivity, specificity and accuracy of senior colposcopists to diagnose histologic CIN 2+ were 80.0% (95% CI 59.30, 93.17), 71.07% (95% CI 62.13, 78.95), and 72.60% (95% CI 64.61, 79.65), and for junior colposcopists were 59.46% (95% CI 42.10, 75.25), 76.72% (95% CI 67.97, 84.04), and 72.55% (95% CI 64.76, 79.45) respectively. The overall sensitivity, specificity, and accuracy of colposcopy to diagnose histologic CIN 2+ were 66.67% (95% CI 53.66, 78.05), 73.73% (95% CI 67.63, 79.23), and 72.24% (95% CI 66.79, 77.24) respectively.

Conclusions

In this study, the senior and junior colposcopists had a comparable colposcopic accuracy to diagnose histologic CIN 2+, whereas senior had a higher sensitivity but a lower specificity than junior colposcopists.
Prevalence of short and long sleep duration: Ravansar NonCommunicable Disease (RaNCD) cohort study
Authors: Najafi Arezu , Akbarpour Samaneh , Najafi Farid , Safari-Faramani Roya , Sadeghniiat-Haghighi Khosro , Aghajani Faezeh , Asgari Samaneh , Aleebrahim Forugh , Nakhostin-Ansari Amin
Published: August 2022

Background

Prevalence of short and long sleep duration varies in different countries and changes over time. There are limited studies on Iranians’ sleep duration, and we aimed to evaluate the prevalence of short and long sleep duration and associated factors among people living in Kermanshah, Iran.

Methods

This population-based cross-sectional study was conducted between November 2014 and February 2017. Data was collected from 10,025 adults aged 35 to 65 years using census sampling, and we evaluated the short and long sleep duration (≤ 6 and ≥ 9 h, respectively) and its relation with the socio-demographic factors and health-related status of the participants.

Results

Mean age of participants was 48.1 years (standard deviation = 8.2), and 47.4% of participants were male. Of our participants, 11.6% had short, and 21.9% had long sleep duration. Age ≥ 50 years, female gender, being single, mobile use for longer than 8 h per day, working in night shifts, moderate and good levels of physical activity, BMI ≥ 30, past smoking, and alcohol use were associated with short sleep duration (P < 0.05). Female gender and living in rural areas were associated with long sleep duration (P < 0.05).

Conclusion

In the Ravansar population, short and long sleep duration are prevalent, with long sleep duration having higher prevalence. People at risk, such as night shift workers, as well as modifiable factors, such as mobile phone use, can be targeted with interventions to improve sleep hygiene.
Developmental trajectories of tobacco use and risk factors from adolescence to emerging young adulthood: a population-based panel study
Authors: Kim Seong Yeon , Cho Sung-il
Published: August 2022

Background

Adolescence to young adulthood is a critical developmental period that determines lifelong patterns of tobacco use. We examined the longitudinal trajectories of tobacco use, and risk factors for its use, and explored the association between the trajectories of mobile phone dependency and smoking throughout the life-course among adolescents and young adults.

Methods

Data of 1,723 subjects (853 boys and 870 girls) were obtained from six waves of the Korean Children and Youth Panel Survey (mean age = 13.9–19.9 years). To identify trajectories of smoking and mobile phone dependency, group-based trajectory modelling (GBTM) was conducted. A multinomial logistic regression analysis was performed to identify the characteristics of the trajectory groups.

Results

GBTM identified four distinct smoking trajectories: never smokers (69.1%), persistent light smokers (8.7%), early established smokers (12.0%), and late escalators (10.3%). Successful school adjustment decreased the risk of being an early established smoker (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.27–0.78). The number of days not supervised by a guardian after school was positively associated with the risk of being an early established smoker (OR 1.96, 95% CI 1.23–3.13). Dependency on mobile phones throughout the life-course was positively associated with the risk of being a persistent light smoker (OR 4.04, 95% CI 1.32–12.34) or early established smoker (OR 8.18, 95% CI 4.04–16.56).

Conclusions

Based on the group-based modeling approach, we identified four distinctive smoking trajectories and highlight the long-term effects of mobile phone dependency, from early adolescence to young adulthood, on smoking patterns.
Introduction of a modified single stage reconstruction technique of male penopubic epispadias
Authors: Bitaraf Masoud , Mahdavi Sharif Pouya , Torabinavid Parham , Kajbafzadeh Abdol-Mohammad
Published: August 2022

Objective

To represent the long-term outcomes of our modified single-stage technique for the reconstruction of isolated penopubic epispadias in male patients.

Patients and methods

Data from 113 patients were obtained from bladder-exstrophy-epispadias database of our tertiary center. A total of seven boys with isolated penopubic epispadias with no prior history of surgery and any other anomaly underwent our modified surgical approach from February 1997 to September 2019. The mean ± SD age at surgery was 6.5 ± 2.4 years. Volitional voiding status and cosmetic appearance were evaluated at each follow-up interval. Postoperative follow-up was performed at quarterly intervals in the first year and once a year in subsequent years.

Results

The mean ± SD of follow-up was 8.5 ± 6 years. All boys who were incontinent achieved urinary control and the ability of normal transurethral micturition following the surgery. Four boys became completely dry, and the other three attained social dryness. Postoperative mean (SD) bladder capacity was significantly increased from 54.5 (11) to 124 (40.0) within 6 months, and to 194 (47.5) at 18 months after surgery. Dorsal curvature has been resolved in all cases, and no postoperative complications were noted except for surgical site infection in one patient treated with antibiotics and bilateral vesicourethral reflux resolved after injection of bulking agents. Four patients had normal erectile function and ejaculation, while the others have not reached puberty yet. Moreover, none of the patients developed urethrocutaneous fistula, stricture, or penile ischemia.

Conclusion

The present findings suggest the safety and effectiveness of the combination of single-stage urethro-genitoplasty, bladder neck plication, and fat pad pedicled flap in management of boys with isolated penopubic epispadias that can lead to the achievement of urinary control, acceptable sexual function, and cosmetically satisfactory genitalia. Minimal morbidity, low complication rate, and promising outcomes are essential factors, supporting the notion of introducing this technique as a valid option for management of this entity.
940 nm diode laser induced differentiation of human adipose derived stem cells to temporomandibular joint disc cells
Authors: Karic Vesna , Chandran Rahul , Abrahamse Heidi
Published: August 2022

Background

Temporomandibular disorder (TMD) refers to a group of disorders that affect temporomandibular joint (TMJ) and its associated muscles with very limited treatment options. Stem cell research is emerging as one of the promising fields in the treatment of degenerative diseases. The ability of human adipose derived stem cells to differentiate into many cell types is driving special interest in several disease management strategies. Photobiomodulation has enhanced the role of these stem cells through their ability to promote cell proliferation and differentiation. Hence, this study examined the differentiation potential of human adipose derived stem cells (ADSCs) into fibroblasts and chondrocytes using a 940 nm diode laser for possible TMD therapy.

Materials and methods

ADSCs were cultured at different seeding densities and for different time intervals. After irradiation at 24, 48, 72 h, 1, 2 and 3 weeks, ADSC viability and morphological changes were assessed in groups with and without basic fibroblast growth factor. Additionally, the level of adenosine triphosphate (ATP) in the cells was also recorded. The differentiated fibroblasts and chondrocytes were characterized with flow cytometry and immunofluorescence techniques, at 1- and 2-weeks post-irradiation.

Results

Increased ATP proliferation and cell viability above 90% were observed in all post-irradiation experimental groups. Post irradiation results from flow cytometry and immunofluorescence at 1- and 2‐weeks confirmed the expression of chondrogenic and fibroblastic cell surface markers.

Conclusion

This study describes stimulatory techniques utilized to differentiate ADSCs into fibroblastic and chondrogenic phenotypes using diode lasers at 940 nm. The study proposes a new treatment model for patients with degenerative disc diseases of the TMJ. The study will offer new possibilities in tissue engineering and TMJ disc management through photobiomodulation of ADSCs using a 940 nm diode laser.
Performance of IRBs in China: a survey on IRB employees and researchers’ experiences and perceptions
Authors: Liu Xing , Wu Ying , Yang Min , Li Yang , Khoshnood Kaveh , Luo Esther , Li Lun , Wang Xiaomin
Published: August 2022

Background

Performance evaluation is vital for IRB operations. As the number of IRBs and their responsibilities in reviewing and supervising clinical research grow in China, there is a significant need to evaluate their performances. To date, little research has examined IRB performance within China. The aim of this study was to ascertain the perspectives and experiences of IRB employees and researchers to (1) understand the current status of IRBs; (2) compare collected results with those of other countries; and (3) identify shortcomings to improve IRB performance.

Methods

This study was conducted in China from October 2020 to September 2021, using an online survey with the IRB-researcher assessment tool-Chinese version.

Results

757 respondents were included in the analysis and classified into IRB employees, researchers, or those who are both IRB employees and researchers. Overall, the score for an ideal IRB was significantly higher than that of an actual IRB. Compared to the US National Validation study, Chinese participants and American participants both agree and differ in their perspectives on the most and least important ideal items.

Conclusion

This investigation provides a benchmark of the perceived performance of actual IRBs in China. IRBs in China can be precisely adjusted by targeting identified areas of weakness to improve their performances.
How to establish workplace learning in long-term care: results from a World Café dialogue
Authors: van Lierop Merel E. A. , Meijers Judith M. M. , van Rossum Erik , Rutten Johanna E. R. , Thoma-Lürken Theresa , Zwakhalen Sandra M. G.
Published: August 2022

Background

As long-term care continues to change, the traditional way of learning for work purposes is no longer sufficient. Long-term care organisations need to become ‘learning organisations’ and facilitate workplace learning for nursing staff teams. Therefore, insight is needed into what conditions are important for establishing workplace learning. The aim and objective of this article is to gain insight into necessary individual, team and organisational conditions for nursing staff to enhance workplace learning in long-term care settings.

Methods

This study is a qualitative explorative study. A World Café method was used to host group dialogues in which participants (n = 42) discussed certain questions. Group dialogues were held for the nursing home and community care setting separately due to organisational differences. Nursing staff, experts in workplace learning, educational staff, client representatives and experts in the field of work and organisation in healthcare organisations were invited to a Dutch long-term care organisation to discuss questions of interest. Data were analysed using theme-based content analysis.

Results

Overall themes concerning individual, team and organisational conditions for workplace learning included: facilitating characteristics (e.g. to be given time and room for [team] development); behavioural characteristics (e.g. an open attitude); context and culture (e.g. feeling safe); cooperation and communication (e.g. giving/receiving feedback); and knowledge and skills (e.g. acquiring knowledge from each other). No major differences were found between settings.

Conclusions

By assessing the themes at the individual, team and organisational level regarding nursing staff, the current workplace learning situation, and its possible improvements, can be detected.
Barriers and facilitators of access to HIV prevention, care, and treatment services among people living with HIV in Kerman, Iran: a qualitative study
Authors: Jaafari Zahra , McFarland Willi , Eybpoosh Sana , Tabatabaei Seyed Vahid Ahmadi , Bafti Mehdi Shafiei , Ranjbar Ebrahim , Sharifi Hamid
Published: August 2022

Background

Low access to HIV prevention, care, and treatment services among people living with HIV (PLWH) is a barrier to the control of the epidemic worldwide. The present study aimed to assess the barriers and facilitators to HIV services among PLWH in Kerman, Iran.

Methods

In this qualitative study, a convenience sample of 25 PLWH who had received HIV prevention, treatment, or care services, and six PLWH who had not yet received services were recruited between August-October 2020. Data were collected using a semi-structured, face-to-face interview. Data were examined by inductive content analysis using MAXQDA 10 software.

Results

Nine categories of facilitators and 11 categories of barriers to HIV services were identified. Facilitating factors included: maintaining health status, feeling scared, trust in the health system, how they were treated by service providers, provision of suitable hours by the service provider center, changing attitudes towards HIV in society, acceptance of the disease by the patient's family, hope for the future and feeling the need for consulting services. Barriers included financial problems, side effects and belief in efficacy, distance and transportation problems, fear of being recognized, stigma towards PLWH, organization of services, improper treatment by service providers, unsuitable hours by the service provider center, lack of trust in the health system, lack of family support, and inadequate or low-quality service.

Conclusion

Many facilitators and barriers to HIV prevention, treatment, and care are amenable to change and better management by healthcare and service providers. Addressing these factors is likely to increase the willingness to use services by those who have never previously accessed them.
Transcriptional response of individual Hawaiian Culex quinquefasciatus mosquitoes to the avian malaria parasite Plasmodium relictum
Authors: Ferreira Francisco C. , Videvall Elin , Seidl Christa M. , Wagner Nicole E. , Kilpatrick A. Marm , Fleischer Robert C. , Fonseca Dina M.
Published: August 2022

Background

Plasmodium parasites that cause bird malaria occur in all continents except Antarctica and are primarily transmitted by mosquitoes in the genus Culex. Culex quinquefasciatus, the mosquito vector of avian malaria in Hawaiʻi, became established in the islands in the 1820s. While the deadly effects of malaria on endemic bird species have been documented for many decades, vector-parasite interactions in avian malaria systems are relatively understudied.

Methods

To evaluate the gene expression response of mosquitoes exposed to a Plasmodium infection intensity known to occur naturally in Hawaiʻi, offspring of wild-collected Hawaiian Cx. quinquefasciatus were fed on a domestic canary infected with a fresh isolate of Plasmodium relictum GRW4 from a wild-caught Hawaiian honeycreeper. Control mosquitoes were fed on an uninfected canary. Transcriptomes of five infected and three uninfected individual mosquitoes were sequenced at each of three stages of the parasite life cycle: 24 h post feeding (hpf) during ookinete invasion; 5 days post feeding (dpf) when oocysts are developing; 10 dpf when sporozoites are released and invade the salivary glands.

Results

Differential gene expression analyses showed that during ookinete invasion (24 hpf), genes related to oxidoreductase activity and galactose catabolism had lower expression levels in infected mosquitoes compared to controls. Oocyst development (5 dpf) was associated with reduced expression of a gene with a predicted innate immune function. At 10 dpf, infected mosquitoes had reduced expression levels of a serine protease inhibitor, and further studies should assess its role as a Plasmodium agonist in C. quinquefasciatus. Overall, the differential gene expression response of Hawaiian Culex exposed to a Plasmodium infection intensity known to occur naturally in Hawaiʻi was low, but more pronounced during ookinete invasion.

Conclusions

This is the first analysis of the transcriptional responses of vectors to malaria parasites in non-mammalian systems. Interestingly, few similarities were found between the response of Culex infected with a bird Plasmodium and those reported in Anopheles infected with human Plasmodium. The relatively small transcriptional changes observed in mosquito genes related to immune response and nutrient metabolism support conclusions of low fitness costs often documented in experimental challenges of Culex with avian Plasmodium.
Predictive ability of viscoelastic testing using ClotPro® for short-term outcome in patients with severe Covid-19 ARDS with or without ECMO therapy: a retrospective study
Authors: Heubner Lars , Greiner Marvin , Vicent Oliver , Beyer-Westendorf Jan , Tiebel Oliver , Scholz Ute , Güldner Andreas , Mirus Martin , Fries Dietmar , Koch Thea , Spieth Peter Markus
Published: August 2022

Background

SARS-CoV-2 infections are suspected to trigger the coagulation system through various pathways leading to a high incidence of thromboembolic complications, hypercoagulation and impaired fibrinolytic capacity were previously identified as potentially mechanisms. A reliable diagnostic tool for detecting both is still under discussion. This retrospective study is aimed to examine the prognostic relevance of early viscoelastic testing compared to conventional laboratory tests in COVID-19 patients with acute respiratory distress syndrome (ARDS).

Methods

All mechanically ventilated patients with COVID-19 related ARDS treated in our intensive care unit (ICU) between January and March 2021 were included in this study. Viscoelastic testing (VET) was performed using the ClotPro® system after admission to our ICU. Prevalence of thromboembolic events was observed by standardized screening for venous and pulmonary thromboembolism using complete compression ultrasound and thoracic computed tomography pulmonary angiography at ICU admission, respectively. We examined associations between the severity of ARDS at admission to our ICU, in-hospital mortality and the incidence of thromboembolic events comparing conventional laboratory analysis and VET. ECMO related coagulopathy was investigated in a subgroup analysis. The data were analyzed using the Mann–Whitney U test.

Results

Of 55 patients enrolled in this study, 22 patients required treatment with ECMO. Thromboembolic complications occurred in 51% of all patients. Overall hospital mortality was 55%. In patients with thromboembolic complications, signs of reduced fibrinolytic capacity could be detected in the TPA assay with prolonged lysis time, median 460 s (IQR 350–560) vs 359 s (IQR 287–521, p = 0.073). Patients with moderate to severe ARDS at admission to our ICU showed increased maximum clot firmness as a sign of hypercoagulation in the EX-test (70 vs 67 mm, p < 0.05), FIB-test (35 vs 24 mm, p < 0.05) and TPA-test (52 vs 36 mm, p < 0.05) as well as higher values of inflammatory markers (CRP, PCT and IL6). ECMO patients suffered more frequently from bleeding complications (32% vs 15%).

Conclusion

Although, the predictive value for thromboembolic complications or mortality seems limited, point-of-care viscoelastic coagulation testing might be useful in detecting hypercoagulable states and impaired fibrinolysis in critically ill COVID-19 ARDS patients and could be helpful in identifying patients with a potentially very severe course of the disease.
Soil conditions on bacterial wilt disease affect bacterial and fungal assemblage in the rhizosphere
Authors: Liu Xiaojiao , Liu Liehua , Gong Jie , Zhang Lixin , Jiang Qipeng , Huang Kuo , Ding Wei
Published: August 2022

Natural soil has the ability to suppress the soil-borne pathogen to a certain extent, and the assemblage of soil microbiome plays a crucial role in maintaining such ability. Long-term monoculture accelerates the forms of soil microbiome and leads to either disease conducive or suppressive soils. Here, we explored the impact of soil conditions on bacterial wilt disease (healthy or diseased) under long-term tobacco monoculture on the assemblage of bacterial and fungal communities in bulk and rhizosphere soils during the growth periods. With Illumina sequencing, we compared the bacterial and fungal composition of soil samples from tobacco bacterial wilt diseased fields and healthy fields in three growth periods. We found thatProteobacteriaandAscomycotawere the most abundant phylum for bacteria and fungi, respectively. Factors of soil conditions and tobacco growth periods can significantly influence the microbial composition in bulk soil samples, while the factor of soil conditions mainly determined the microbial composition in rhizosphere soil samples. Next, rhizosphere samples were further analyzed with LEfSe to determine the discriminative taxa affected by the factor of soil conditions. For bacteria, the genusRalstoniawas found in the diseased soils, whereas the genusFlavobacteriumwas the only shared taxon in healthy soils; for fungi, the genusChaetomiumwas the most significant taxon in healthy soils. Besides, network analysis confirmed that the topologies of networks of healthy soils were higher than that of diseased soils. Together, our results suggest that microbial assemblage in the rhizosphere will be largely affected by soil conditions especially after long-term monoculture.
What is the impact of SARS-CoV-2 pandemic on antimicrobial stewardship programs (ASPs)? The results of a survey among a regional network of infectious disease centres
Authors: Comelli Agnese , Genovese Camilla , Lombardi Andrea , Bobbio Chiara , Scudeller Luigia , Restelli Umberto , Muscatello Antonio , Antinori Spinello , Bonfanti Paolo , Casari Salvatore , Castagna Antonella , Castelli Francesco , Monforte Antonella d’Arminio , Franzetti Fabio , Grossi Paolo , Lupi Matteo , Morelli Paola , Piconi Stefania , Puoti Massimo , Pusterla Luigi , Regazzetti Angelo , Rizzi Marco , Rusconi Stefano , Zuccaro Valentina , Gori Andrea , Bandera Alessandra ,   the ASP Lomb Study Group, Giacomelli Andrea , Rossi Marianna , Bruno Raffaele , Garilli Silvia , Marco Ripa , Signorini Liana , Bai Francesca , Pan Angelo , Merli Marco , Ricaboni Davide , Molteni Chiara , Benatti Simone Vasilij , Castiglioni Barbara , Rovelli Cristina , Piazza Manuela , Franzetti Marco
Published: August 2022

Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.
Clustered and dispersed: exploring the morphological evolution of traditional villages based on cellular automaton
Authors: Yang Xi , Pu Fuan
Published: August 2022

The spatial pattern of traditional villages can be generally divided into two main types: clustered and dispersed. In order to explore and compare the spatial evolutionary characteristics of different village patterns, and provide a reliable basis for spatial planning, a universal Cellular Automaton (CA) model was built and applied in different spatial simulations. Through model comparison, it was established that: (1) both types of villages have developed in the same cyclical changing mode of "outlying + edge-expansion", which was probably rooted in the inherent spatial sense of the ethnic group inhabiting village types; (2) the spatial growth of the clustered village was more relevant to the distribution structure of pre-existing buildings, whereas the spatial sprawl of a dispersed one was more connected to external natural factors; and (3) the development of every economic unit in a dispersed village was strictly restricted to the building area, and to the proportion of population inhabiting farmland area. Although village patterns developed under the same logical framework rooted in ethnic culture, their development tendency varied, with different dynamic mechanisms and constraints.
Novel nannofossils extraction methods from paintings, coupled with GC–MS for provenance determination and binder analysis
Authors: Jaques Victory Armida Janine , Trubač Jakub , Rathouský Jiří , Cajthaml Tomáš , Holcová Katarína
Published: August 2022

The use of calcareous nannofossils for provenance analysis is a new-old topic for cultural heritage. Several studies have already mentioned it for ceramic, but less for paintings. Preparatory layers of the paintings are often made with chalk, which is composed of microfossils. To extract a calcareous nannofossils assemblage from a painting layer, we need to disaggregate it. The method is to plunge the micro-samples into water and heat it if water alone does not work. The disaggregation process takes a long time and is not efficient in terms of quantitative results. In this work, we aimed to develop a disaggregation method that increases the number of determinable nannofossils extracted from a painting micro-sample. As these samples are valuable and unique, we decided that a combination of analyses on the disaggregated micro-sample should be tried to extract the most information from it. We studied the possibility of binder determination by gas chromatography–mass spectrometer after the nannofossils assemblage extraction on the residual liquid from the disaggregation. The method we are presenting is easy to apply, has a high disaggregation rate for most paintings, and a low impact on binders fatty acids for their determination.
Indication-wide drug pricing: Insights from the pharma market
Authors: Siegmeier Florian , Büssgen Melanie
Published: August 2022

Background

Pharmaceutical spending has been increasing rapidly for years and is higher than ever before. To control the rising costs, countries are implementing regulatory frameworks such as (internal) reference pricing, price cuts or generics substitution. Internal reference pricing establishes a reference price within a country which serves as the maximum level of reimbursement for a group of pharmaceuticals. Price setting in the German market is especially relevant for many European countries, which use Germany as a reference country for their own price setting.

Methods

We evaluate pharmaceutical price dynamics for not reference priced pharmaceuticals (NRPs) as well as for reference priced pharmaceuticals (RPs) in Germany—referring to the internal reference price system. 64,862 medication packs have been extracted from the German pharmaceutical pricing register Lauer-Taxe. For each pack, we extracted detailed data on the company, manufacturer rebates, pharmacy retail prices, reference prices, co-payments, import quotas, and discount agreements. We then investigated price setting and dynamics of NRPs vs. RPs for all 14 indication areas by ATC code level 1.

Results

The average manufacturer price per pack was 604.84€ for NRPs and 112.11€ for RPs. Similar differences were found for the wholesale price and the pharmacy retail price. The reference price was—as expected—0.00€ for NRPs, and 154.40€ for RPs. NRP packs were imported in 42.38%, while RP packs were imported only in 24.62%. Highest average pharmacy retail prices could be found in the therapeutic areas ‘antineoplastic and immunomodulating agents’ (1711.47€), ‘systemic hormonal preparations’ (1331.95€), and ‘blood and blood forming organs’ (1260.58€). We detected high fluctuations in pharmacy retail prices per indication, as well as for reference prices per indication. The indications with the highest number of reference price regulated medical packs are ‘cardiovascular system’, ‘musculo-skeletal system’, and ‘nervous system’. Highest co-payments were found in the indications ‘antineoplastic and immunomodulating agents’, ‘blood and blood forming organs’, and ‘antiinfectives for systemic use’.

Conclusion

Price setting and price dynamics vary substantially between NRP and RP medication packs. Further, we saw major differences across all indication areas as well as when comparing medication packs launched by top 20 pharma companies vs. the rest.
Efficient biodegradation of straw and persistent organic pollutants by a novel strategy using recombinant Trichoderma reesei
Authors: Xia Ying , Lin Xinda
Published: August 2022

Efficient biodegradation of lignocellulosic biomass needs a battery of enzymes targeting cellulose, hemicellulose, and lignin. In this study, recombinant Trichoderma reesei ZJ-09 with Pycnoporus sanguineus laccase gene was used to degrade rice straw by in situ production of laccase, xylanase, and cellulases under solid-state fermentation (SSF). Effects of parameters on key enzymes (cellulase, xylanase, and laccase) in biodegradation during SSF were investigated. Under the optimized SSF conditions, the FPA, xylanase activity, and laccase activity reached 110.47 FPU/g, 5787.59 IU/g, and 24.45 IU/g, respectively, on day 12. The obtained recombinant T. reesei SSF system achieved efficient degradation of rice straw with the final mass loss up to 51.16% which was 1.4-fold higher than the host strain. Further, bioconversion of rice straw into a novel laccase-enriched koji for persistent organic pollutants bioremediation (LKPB) was conducted by the optimized SSF system. LKPB was found to degrade persistent organic pollutants (POPs) effectively without the addition of mediators. 4-h removal rates of three POPs mediated by LKPB (87.21% for 2,4,5-trichlorophenol, 92.45% for nonylphenol, and 90.73% for oxytetracycline) were comparable to those achieved by laccase-co-mediator system. The newly established recombinant T. reesei SSF system could be potential to effectively degrade lignocellulosic wastes as well as organic pollutants.

Graphical abstract
Development of highly efficient whole-cell catalysts of cis-epoxysuccinic acid hydrolase by surface display
Authors: Zhou Rui , Dong Sheng , Feng Yingang , Cui Qiu , Xuan Jinsong
Published: August 2022

Bacterial cis-epoxysuccinic acid hydrolases (CESHs) are intracellular enzymes used in the industrial production of enantiomeric tartaric acids. The enzymes are mainly used as whole-cell catalysts because of the low stability of purified CESHs. However, the low cell permeability is the major drawback of the whole-cell catalyst. To overcome this problem, we developed whole-cell catalysts using various surface display systems for CESH[L] which produces L(+)-tartaric acid. Considering that the display efficiency depends on both the carrier and the passenger, we screened five different anchoring motifs in Escherichia coli. Display efficiencies are significantly different among these five systems and the InaPbN-CESH[L] system has the highest whole-cell enzymatic activity. Conditions for InaPbN-CESH[L] production were optimized and a maturation step was discovered which can increase the whole-cell activity several times. After optimization, the total activity of the InaPbN-CESH[L] surface display system is higher than the total lysate activity of an intracellular CESH[L] overexpression system, indicating a very high CESH[L] display level. Furthermore, the whole-cell InaPbN-CESH[L] biocatalyst exhibited good storage stability at 4 °C and considerable reusability. Thereby, an efficient whole-cell CESH[L] biocatalyst was developed in this study, which solves the cell permeability problem and provides a valuable system for industrial L(+)-tartaric acid production.

Graphical Abstract
Effect of bovine milk fat-based infant formulae on microbiota, metabolites and stool parameters in healthy term infants in a randomized, crossover, placebo-controlled trial
Authors: Looijesteijn Ellen , Brouwer Rutger W. W. , Schoemaker Ruud J. W. , Ulfman Laurien H. , Ham Stephanie L. , Jeurink Prescilla , Karaglani Eva , van IJcken Wilfred F. J. , Manios Yannis
Published: August 2022

Background

Natural enrichment of sn-2 palmitate content of infant formulae by using bovine milk fat is known to reduce formation of faecal fatty acid soaps and to improve stool consistency, but effects on gut microbiota composition are unknown. The purpose of this study was to test the influence of milk fat-based formula high in sn-2 palmitate on the infants’ gut microbiota composition and to confirm the beneficial effects of the formula on formation of faecal fatty acid soaps and stool consistency.

Methods

Twenty-two healthy term, formula-fed infants were enrolled in a single-blinded randomized, crossover, placebo-controlled trial. After a 2-week run-in period, infants received either a 50% milk fat-based formula containing 39% sn-2 palmitate (MF) or a vegetable fat-based formula (VF) containing 10% sn-2 palmitate in a 2 × 2-week crossover design. Faecal microbiota composition was the primary outcome of the study. Other outcomes included faecal fatty acid soap excretion, calcium excretion, gut comfort parameters and faecal metabolites.

Results

Microbiota analysis showed that bifidobacteria dominated the gut microbiota of most infants. Neither alpha- nor beta-diversity was significantly influenced by the intervention. Also, abundance of metabolic pathways was independent of the intervention. The MF formula resulted in significantly lower faecal levels of palmitic acid soap (p = 0.0002) and total fatty acid soaps (p = 0.0001) than the VF formula. Additionally, calcium excretion and palmitic acid concentration were significantly (p = 0.0335) lower in stool samples after MF intervention. Furthermore, a significant physiological effect on softer stools was observed in the MF intervention compared to the VF intervention (p = 0.02).

Of the 870 measured faecal metabolites, 190 were significantly different after MF and VF intervention (FDR corrected p < 0.05). Most of these were found at higher levels after MF intervention, potentially indicative of the complex structure of milk fat. Metabolites with more than twofold change between interventions were mostly lipid-derived and included several milk fat-specific fatty acids.

Conclusions

Replacing part of the vegetable fat in infant formula with bovine milk fat with high sn-2 palmitate levels did not change the microbiota composition, although a reduction in faecal palmitate soaps, total fatty acid soaps and calcium excretion while improving stool consistency in the MF intervention was confirmed. In addition, 190 faecal metabolites were significantly different, many related to the fat source.

Trial registration

Netherlands Trial Registry Identifier: NL7815 19/06/2019.
Computation of contrast-enhanced perfusion using only two CT scan phases: a proof-of-concept study on abdominal organs
Authors: Cressoni Massimo , Cozzi Andrea , Schiaffino Simone , Cadringher Paolo , Vitali Paolo , Basso Gianpaolo , Ippolito Davide , Sardanelli Francesco
Published: August 2022

Background

Computed tomography perfusion imaging (CTPI) by repeated scanning has clinical relevance but implies relatively high radiation exposure. We present a method to measure perfusion from two CT scan phases only, considering tissue enhancement, feeding vessel (aortic) peak enhancement, and bolus shape.

Methods

CTPI scans (each with 40 frames acquired every 1.5 s) of 11 patients with advanced hepatocellular carcinoma (HCC) enrolled between 2012 and 2016 were retrospectively analysed (aged 69 ± 9 years, 8/11 males). Perfusion was defined as the maximal slope of the time-enhancement curve divided by the peak enhancement of the feeding vessel (aorta). Perfusion was computed two times, first using the maximum slope derived from all data points and then using the peak tissue enhancement and the bolus shape obtained from the aortic curve.

Results

Perfusion values from the two methods were linearly related (r2 = 0.92, p < 0.001; Bland–Altman analysis bias -0.12). The mathematical model showed that the perfusion ratio of two ROIs with the same feeding vessel (aorta) corresponds to their peak enhancement ratio (r2 = 0.55, p < 0.001; Bland–Altman analysis bias -0.68). The relationship between perfusion and tissue enhancement is predicted to be linear in the clinical range of interest, being only function of perfusion, peak feeding vessel enhancement, and bolus shape.

Conclusions

This proof-of-concept study showed that perfusion values of HCC, kidney, and pancreas could be computed using enhancement measured only with two CT scan phases, if aortic peak enhancement and bolus shape are known.
An extremely rare presentation of non-Hodgkin lymphoma in the head and neck: a case report
Authors: Nasirmohtaram Sevil , Mesbah Alireza , Mazloom Farnaz
Published: August 2022

Background

Non-Hodgkin lymphoma (NHL) frequently presents as extra-nodal involvement, although primary diffuse large B cell lymphoma of extra-nodal origin is a distinct entity. Different subtypes may have propensity for specific anatomic locations. In the head and neck region, diffuse large B cell lymphoma (DLBCL) is most commonly presented in the paranasal sinuses, jaws, and Waldeyer’s ring. DLBCL involving fibroadipose tissue and presenting as an extra-nodal mass is extremely unusual, particularly in the head and neck region.

Case presentation

We will present a case of forehead mass as presenting features of a highly aggressive B cell lymphoma.

Conclusion

Although soft tissue DLBCL presenting as scalp mass is rare, it should be considered in differential diagnosis of every soft tissue lump.
Experimental and numerical study of novel Coanda-based unmanned aerial vehicle
Authors: Siddiqi Zaid , Lee Jin W.
Published: August 2022

Conventional Coanda-based unmanned aerial vehicles (UAV) experience thrust losses in the radial direction. To address these losses, a rectangular, linear arrangement of the Coanda surface was adopted in the proposed novel design. This arrangement minimizes the area change in the radial direction to recover such thrust losses. A prototype of the proposed UAV structure was 3D printed and assembled with a single 9-inch propeller. Performance characteristics of the UAV were evaluated through static testing on a dynamometer under different loading conditions. Experimental results were validated through computational fluid dynamics (CFD) simulations, using the k-ε realizable turbulence model, while the multiple reference frame (MRF) approach was applied in steady state. CFD simulations provided good overall agreement with experimental results having errors less than 8%. Numerical comparison between the novel Coanda design and a conventional Coanda design, having similar radial dimensions, showed that the novel design offered an overall 17% improvement in thrust per the side surface area, thus demonstrating an effective reduction of thrust losses in the radial direction.
The Cytoskeletal Transport Protein, Secretagogin, Is Essential for Diurnal Glucagon-like Peptide-1 Secretion in Mice
Authors: Biancolin Andrew David , Srikrishnaraj Arjuna , Jeong Hyerin , Martchenko Alexandre , Brubaker Patricia Lee
Published: August 2022

The intestinal L-cell incretin, glucagon-like peptide-1 (GLP-1), exhibits a circadian pattern of secretion, thereby entraining diurnal insulin release. Secretagogin (Scgn), an actin-binding regulatory protein, is essential for the temporal peak of GLP-1 secretion in vitro. To interrogate the role of Scgn in diurnal GLP-1 secretion in vivo, peak and trough GLP-1 release were evaluated in knockout mice (Scgn−/−, Gcg-CreERT2/+; Scgnfl/fl and Vil-CreERT2/+; Scgnfl/fl), and RNA sequencing (RNA-Seq) was conducted in Scgn knockdown L-cells. All 3 knockout models demonstrated loss of the diurnal rhythm of GLP-1 secretion in response to oral glucose. Gcg-CreERT2/+; Scgnfl/fl mice also lost the normal pattern in glucagon secretion, while Scgn−/− and Vil-CreERT2/+; Scgnfl/fl animals demonstrated impaired diurnal secretion of the related incretin, glucose-dependent insulinotrophic polypeptide. RNA-Seq of mGLUTag L-cells showed decreased pathways regulating vesicle transport, transport and binding, and protein-protein interaction at synapse, as well as pathways related to proteasome-mediated degradation including chaperone-mediated protein complex assembly following Scgn knockdown. Scgn is therefore essential for diurnal L-cell GLP-1 secretion in vivo, likely mediated through effects on secretory granule dynamics.