bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear transport genes recurrently duplicate by means of RNA intermediates in Drosophila but not in other insects
Authors: Mirsalehi Ayda , Markova Dragomira N. , Eslamieh Mohammadmehdi , Betrán Esther
Published: December 2021

Background

The nuclear transport machinery is involved in a well-known male meiotic drive system in Drosophila. Fast gene evolution and gene duplications have been major underlying mechanisms in the evolution of meiotic drive systems, and this might include some nuclear transport genes in Drosophila. So, using a comprehensive, detailed phylogenomic study, we examined 51 insect genomes for the duplication of the same nuclear transport genes.

Results

We find that most of the nuclear transport duplications in Drosophila are of a few classes of nuclear transport genes, RNA mediated and fast evolving. We also retrieve many pseudogenes for the Ran gene. Some of the duplicates are relatively young and likely contributing to the turnover expected for genes under strong but changing selective pressures. These duplications are potentially revealing what features of nuclear transport are under selection. Unlike in flies, we find only a few duplications when we study the Drosophila duplicated nuclear transport genes in dipteran species outside of Drosophila, and none in other insects.

Conclusions

These findings strengthen the hypothesis that nuclear transport gene duplicates in Drosophila evolve either as drivers or suppressors of meiotic drive systems or as other male-specific adaptations circumscribed to flies and involving a handful of nuclear transport functions.
The theory on and software simulating large-scale genomic data for genotype-by-environment interactions
Authors: Li Xiujin , Song Hailiang , Zhang Zhe , Huang Yunmao , Zhang Qin , Ding Xiangdong
Published: December 2021

Background

With the emphasis on analysing genotype-by-environment interactions within the framework of genomic selection and genome-wide association analysis, there is an increasing demand for reliable tools that can be used to simulate large-scale genomic data in order to assess related approaches.

Results

We proposed a theory to simulate large-scale genomic data on genotype-by-environment interactions and added this new function to our developed tool GPOPSIM. Additionally, a simulated threshold trait with large-scale genomic data was also added. The validation of the simulated data indicated that GPOSPIM2.0 is an efficient tool for mimicking the phenotypic data of quantitative traits, threshold traits, and genetically correlated traits with large-scale genomic data while taking genotype-by-environment interactions into account.

Conclusions

This tool is useful for assessing genotype-by-environment interactions and threshold traits methods.
Evaluation of antimicrobial susceptibility testing of Nocardia spp. isolates by broth microdilution with resazurin and spectrophotometry
Authors: Caso Coelho Vivian , Pereira Neves Samara D’Ajuda , Cintra Giudice Mauro , Benard Gil , Lopes Marta Heloisa , Sato Paula Keiko
Published: December 2021

Background

Nocardia species are ubiquitous in natural environments and can cause nocardiosis. In the present study, the use of Resazurin salt and Spectrophotometry were proposed as alternative methods to reduce subjectivity in the interpretation of susceptibility results to antimicrobials by the broth microdilution method for Nocardia spp.

Results

The susceptibility of Nocardia spp. isolates to Amikacin, Ciprofloxacin, Minocycline and Trimethoprim-Sulfamethoxazole was evaluated by Minimum Inhibitory Concentration (MIC) determinations by the broth microdilution method. To verify cellular growth, the colour-changing dye Resazurin was applied, the Optical Densities were measured on a spectrophotometer, and both were compared to Clinical and Laboratory Standards Institute (CLSI) Gold Standard method (visual MIC determination). Percentages of essential and categorical agreements and interpretative categorical errors were calculated within each method (intra-reading) and between them (inter-reading). The Gold Standard visual reading demonstrated 100% of essential and categorical intra-reading agreements for Amikacin, and there was no error when compared with the alternative methods. For Ciprofloxacin, the comparison between the Gold Standard and the Spectrophotometric reading showed 91.5% of essential agreement. In the categorical intra-reading analysis for Minocycline, there were 88.1 and 91.7% in the Gold Standard and in the Spectrophotometric readings, respectively, and 86.4% of concordance between them. High rates of categorical agreement were also observed on the Trimethoprim-Sulfamethoxazole analyses, with 93.7% for the Gold Standard, 84.9% for the Resazurin readings, and 80.5% between them.

Conclusions

The alternative methods with Resazurin and Spectrophotometric readings showed high agreement rates with the Gold Standard.
Impact of vaccine prioritization strategies on mitigating COVID-19: an agent-based simulation study using an urban region in the United States
Authors: Tatapudi Hanisha , Das Rachita , Das Tapas K.
Published: December 2021

Background

Approval of novel vaccines for COVID-19 had brought hope and expectations, but not without additional challenges. One central challenge was understanding how to appropriately prioritize the use of limited supply of vaccines. This study examined the efficacy of the various vaccine prioritization strategies using the vaccination campaign underway in the U.S.

Methods

The study developed a granular agent-based simulation model for mimicking community spread of COVID-19 under various social interventions including full and partial closures, isolation and quarantine, use of face mask and contact tracing, and vaccination. The model was populated with parameters of disease natural history, as well as demographic and societal data for an urban community in the U.S. with 2.8 million residents. The model tracks daily numbers of infected, hospitalized, and deaths for all census age-groups. The model was calibrated using parameters for viral transmission and level of community circulation of individuals. Published data from the Florida COVID-19 dashboard was used to validate the model. Vaccination strategies were compared using a hypothesis test for pairwise comparisons.

Results

Three prioritization strategies were examined: a minor variant of CDC’s recommendation, an age-stratified strategy, and a random strategy. The impact of vaccination was also contrasted with a no vaccination scenario. The study showed that the campaign against COVID-19 in the U.S. using vaccines developed by Pfizer/BioNTech and Moderna 1) reduced the cumulative number of infections by 10% and 2) helped the pandemic to subside below a small threshold of 100 daily new reported cases sooner by approximately a month when compared to no vaccination. A comparison of the prioritization strategies showed no significant difference in their impacts on pandemic mitigation.

Conclusions

The vaccines for COVID-19 were developed and approved much quicker than ever before. However, as per our model, the impact of vaccination on reducing cumulative infections was found to be limited (10%, as noted above). This limited impact is due to the explosive growth of infections that occurred prior to the start of vaccination, which significantly reduced the susceptible pool of the population for whom infection could be prevented. Hence, vaccination had a limited opportunity to reduce the cumulative number of infections. Another notable observation from our study is that instead of adhering strictly to a sequential prioritizing strategy, focus should perhaps be on distributing the vaccines among all eligible as quickly as possible, after providing for the most vulnerable. As much of the population worldwide is yet to be vaccinated, results from this study should aid public health decision makers in effectively allocating their limited vaccine supplies.
Ethnographic research as an evolving method for supporting healthcare improvement skills: a scoping review
Authors: Black Georgia B. , van Os Sandra , Machen Samantha , Fulop Naomi J.
Published: December 2021

Background

The relationship between ethnography and healthcare improvement has been the subject of methodological concern. We conducted a scoping review of ethnographic literature on healthcare improvement topics, with two aims: (1) to describe current ethnographic methods and practices in healthcare improvement research and (2) to consider how these may affect habit and skill formation in the service of healthcare improvement.

Methods

We used a scoping review methodology drawing on Arksey and O’Malley’s methods and more recent guidance. We systematically searched electronic databases including Medline, PsychINFO, EMBASE and CINAHL for papers published between April 2013 – April 2018, with an update in September 2019. Information about study aims, methodology and recommendations for improvement were extracted. We used a theoretical framework outlining the habits and skills required for healthcare improvement to consider how ethnographic research may foster improvement skills.

Results

We included 274 studies covering a wide range of healthcare topics and methods. Ethnography was commonly used for healthcare improvement research about vulnerable populations, e.g. elderly, psychiatry. Focussed ethnography was a prominent method, using a rapid feedback loop into improvement through focus and insider status. Ethnographic approaches such as the use of theory and focus on every day practices can foster improvement skills and habits such as creativity, learning and systems thinking.

Conclusions

We have identified that a variety of ethnographic approaches can be relevant to improvement. The skills and habits we identified may help ethnographers reflect on their approaches in planning healthcare improvement studies and guide peer-review in this field. An important area of future research will be to understand how ethnographic findings are received by decision-makers.
Feasibility of a hybrid clinical trial for respiratory virus detection in toddlers during the influenza season
Authors: Muñoz-Ramírez Soledad , Escribano-López Begoña , Rodrigo-Casares Vallivana , Vergara-Hernández Carlos , Gil-Mary Desamparados , Sorribes-Monrabal Ignacio , Garcés-Sánchez María , Muñoz-Del-Barrio María-Jesús , Albors-Fernández Ana-María , Úbeda-Sansano María-Isabel , Planelles-Cantarino María-Victoria , Largo-blanco Ester-María , Suárez-Vicent Eva , García-Rubio Javier , Bruijning-Verhagen Patricia , Orrico-Sánchez Alejandro , Díez-Domingo Javier
Published: December 2021

Background

Traditional clinical trials are conducted at investigator sites. Participants must visit healthcare facilities several times for the trial procedures. Decentralized clinical trials offer an interesting alternative. They use telemedicine and other technological solutions (apps, monitoring devices or web platforms) to decrease the number of visits to study sites, minimise the impact on daily routine, and decrease geographical barriers for participants. Not much information is available on the use of decentralization in randomized clinical trials with vaccines.

Methods

A hybrid clinical trial may be assisted by parental recording of symptoms using electronic log diaries in combination with home collected nasal swabs. During two influenza seasons, children aged 12 to 35 months with a history of recurrent acute respiratory infections were recruited in 12 primary health centers of the Valencia Region in Spain. Parents completed a symptom diary through an ad hoc mobile app that subsequently assessed whether it was an acute respiratory infection and requested collection of a nasal swab. Feasibility was measured using the percentage of returned electronic diaries and the validity of nasal swabs collected during the influenza season. Respiratory viruses were detected by real-time PCR.

Results

Ninety-nine toddlers were enrolled. Parents completed 10,476 electronic diaries out of the 10,804 requested (97%). The mobile app detected 188 potential acute respiratory infections (ARIs) and requested a nasal swab. In 173 (92%) ARI episodes a swab was taken. 165 (95.4%) of these swabs were collected at home and 144 (87.3%) of them were considered valid for laboratory testing. Overall, 152 (81%) of the ARIs detected in the study had its corresponding valid sample collected.

Conclusions

Hybrid procedures used in this clinical trial with the influenza vaccine in toddlers were considered adequate, as we diagnosed most of the ARI cases on time, and had a valid swab in 81% of the cases. Hybrid clinical trials improve participant adherence to the study procedures and could improve recruitment and quality of life of the participants and the research team by decreasing the number of visits to the investigator site.

This report emphasises that the conduct of hybrid CTs is a valid alternative to traditional CTs with vaccines. This hybrid CT achieved high adherence of participant to the study procedures.

Trial registration

2019–001186-33 (EudraCT).
Individual and facility-level factors associated with women’s receipt of immediate postpartum family planning counseling in Ethiopia: results from national surveys of women and health facilities
Authors: Mickler Alexandria K. , Karp Celia , Ahmed Saifuddin , Yihdego Mahari , Seme Assefa , Shiferaw Solomon , Zimmerman Linnea
Published: December 2021

Background

Immediate postpartum family planning (IPPFP) helps prevent unintended and closely spaced pregnancies. Despite Ethiopia’s rising facility-based delivery rate and supportive IPPFP policies, the prevalence of postpartum contraceptive use remains low, with little known about disparities in access to IPPFP counseling. We sought to understand if women’s receipt of IPPFP counseling varied by individual and facility characteristics.

Methods

We used weighted linked household and facility data from the national Performance Monitoring for Action Ethiopia (PMA-Ethiopia) study. Altogether, 936 women 5–9 weeks postpartum who delivered at a government facility were matched to the nearest facility offering labor and delivery care, corresponding to the facility type in which each woman reported delivering (n = 224 facilities). We explored women’s receipt of IPPFP counseling and individual and facility-level characteristics utilizing descriptive statistics. The relationship between women’s receipt of IPPFP counseling and individual and facility factors were assessed through multivariate, multilevel models.

Results

Approximately one-quarter of postpartum women received IPPFP counseling (27%) and most women delivered government health centers (59%). Nearly all facilities provided IPPFP services (94%); most had short- and long-acting methods available (71 and 87%, respectively) and no recent stockouts (60%). Multivariate analyses revealed significant disparities in IPPFP counseling with lower odds of counseling among primiparous women, those who delivered vaginally, and women who did not receive delivery care from a doctor or health officer (all p < 0.05). Having never used contraception was marginally associated with lower odds of receiving IPPFP counseling (p < 0.10). IPPFP counseling did not differ by age, residence, method availability, or facility type, after adjusting for other individual and facility factors.

Conclusion

Despite relatively widespread availability of IPPFP services in Ethiopia, receipt of IPPFP counseling remains low. Our results highlight important gaps in IPPFP care, particularly among first-time mothers, women who have never used contraception, women who delivered vaginally, and those who did not receive delivery care from a doctor or health officer. As facility births continue to rise in Ethiopia, health systems and providers must ensure that equitable, high-quality IPPFP services are offered to all women.
Exploring the lived experiences of pregnant women and community health care providers during the pandemic of COVID-19 in Bangladesh through a phenomenological analysis
Authors: Akhter Sadika , Kumkum Feroza Akhter , Bashar Farzana , Rahman Aminur
Published: December 2021

Background

Like many countries, the government of Bangladesh also imposed stay-at-home orders to restrict the spread of severe acute respiratory syndrome coronavirus-2 (COVID-19) in March, 2020. Epidemiological studies were undertaken to estimate the early possible unforeseen effects on maternal mortality due to the disruption of services during the lockdown. Little is known about the constraints faced by the pregnant women and community health workers in accessing and providing basic obstetric services during the pandemic in the country. This study was conducted to explore the lived experience of pregnant women and community health care providers from two southern districts of Bangladesh during the pandemic of COVID-19.

Methods

The study participants were recruited through purposive sampling and non-structured in-depth interviews were conducted. Data was collected over the telephone from April to June, 2020. The data collected was analyzed through a phenomenological approach.

Results

Our analysis shows that community health care providers are working under tremendous strains of work load, fear of getting infected and physical and mental fatigue in a widely disrupted health system. Despite the fear of getting infected, the health workers are reluctant to wear personal protective suits because of gender norms. Similarly, the lived experience of pregnant women shows that they are feeling helpless; the joyful event of pregnancy has suddenly turned into a constant fear and stress. They are living in a limbo of hope and despair with a belief that only God could save their lives.

Conclusion

The results of the study present the vulnerability of pregnant women and health workers during the pandemic. It recognizes the challenges and constraints, emphasizing the crucial need for government and non-government organizations to improve maternal and newborn health services to protect the pregnant women and health workers as they face predicted waves of the pandemic in the future.
Prognostic value and predication model of microvascular invasion in patients with intrahepatic cholangiocarcinoma: a multicenter study from China
Authors: Chen Yifan , Liu Hongzhi , Zhang Jinyu , Wu Yijun , Zhou Weiping , Cheng Zhangjun , Lou Jianying , Zheng Shuguo , Bi Xinyu , Wang Jianming , Guo Wei , Li Fuyu , Wang Jian , Zheng Yamin , Li Jingdong , Cheng Shi , Zeng Yongyi , Liu Jingfeng
Published: December 2021

Background

At present, hepatectomy is still the most common and effective treatment method for intrahepatic cholangiocarcinoma (ICC) patients. However, the postoperative prognosis is poor. Therefore, the prognostic factors for these patients require further exploration. Whether microvascular invasion (MVI) plays a crucial role in the prognosis of ICC patients is still unclear. Moreover, few studies have focused on preoperative predictions of MVI in ICC patients.

Methods

Clinicopathological data of 704 ICC patients after curative resection were retrospectively collected from 13 hospitals. Independent risk factors were identified by the Cox or logistic proportional hazards model. In addition, the survival curves of the MVI-positive and MVI-negative groups before and after matching were analyzed. Subsequently, 341 patients from a single center (Eastern Hepatobiliary Hospital) in the above multicenter retrospective cohort were used to construct a nomogram prediction model. Then, the model was evaluated by the index of concordance (C-Index) and the calibration curve.

Results

After propensity score matching (PSM), Child-Pugh grade and MVI were independent risk factors for overall survival (OS) in ICC patients after curative resection. Major hepatectomy and MVI were independent risk factors for recurrence-free survival (RFS). The survival curves of OS and RFS before and after PSM in the MVI-positive groups were significantly different compared with those in the MVI-negative groups. Multivariate logistic regression results demonstrated that age, gamma-glutamyl transpeptidase (GGT), and preoperative image tumor number were independent risk factors for the occurrence of MVI. Furthermore, the prediction model in the form of a nomogram was constructed, which showed good prediction ability for both the training (C-index = 0.7622) and validation (C-index = 0.7591) groups, and the calibration curve showed good consistency with reality.

Conclusion

MVI is an independent risk factor for the prognosis of ICC patients after curative resection. Age, GGT, and preoperative image tumor number were independent risk factors for the occurrence of MVI in ICC patients. The prediction model constructed further showed good predictive ability in both the training and validation groups with good consistency with reality.
Current pattern of ocular trauma as seen in tertiary institutions in south-eastern Nigeria
Authors: Jac-Okereke Chinwe Cynthia , Jac-Okereke Chukwunonso Azubuike , Ezegwui Ifeoma Regina , Umeh Rich Enujioke
Published: December 2021

Background

Ocular trauma is a leading cause of monocular blindness worldwide and in developing countries, are not only more common but also more severe. Industrialization and urbanization may alter or modify prevalent aetiological factors and the presentation of ocular trauma.

Objective

To determine the current pattern of eye injuries in Teaching Hospitals in Enugu State.

Methods

This prospective cross-sectional descriptive study was carried out at the eye clinics and emergency units of two tertiary institutions in Enugu, Nigeria. Consecutive ocular trauma patients were enrolled over a 5-month period. On presentation, they underwent ocular examination including visual acuity (which was categorized according to the WHO classification of visual impairment and blindness}, anterior and posterior segment examinations. Injuries were grouped using the Birmingham Eye Trauma Terminology system.

Results

Within the study period, 2545 new patients presented to the hospitals where the study was conducted. A total of 89 patients presented with ocular trauma, giving an incidence of 3.5%. The male to female ratio was 1.3:1 and patients aged 10 to 19 years formed the majority (24%). Domestic accidents (22%) were the most common cause of ocular injuries while blunt objects (57%) were the most common agents. Closed globe injuries constituted 76% of all injuries. Forty-three per cent of patients presented within 24 h of injury.

Conclusion

Ocular trauma is still prevalent in South-eastern Nigeria and there has indeed been a change in the pattern as well as the incidence. Assault and road traffic accidents have emerged as important causes of eye injuries. In addition, there has been an improvement in the health-seeking behaviour of people living in Enugu and this may reflect positively on the uptake of recommended preventive strategies.
β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells
Authors: Yuan Xingyue , Ma Xiubin , Yang Lingling , Zhou Qingjun , Li Ya
Published: December 2021

Background

Topical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of β-blocker eye drops on corneal epithelial wound healing.

Methods

Corneal epithelial wound healing models were constructed by epithelial scraping including in the limbal region and unceasingly received eye drops containing 5 mg/mL β-blocker levobunolol, β1-adrenoceptor (β1AR)-specific antagonist atenolol or β2-adrenoceptor (β2AR)-specific antagonist ICI 118, 551. For the migration assay, the murine corneal epithelial stem/progenitor cells (TKE2) were wounded and subsequently incubated with levobunolol, atenolol, or ICI 118, 551. The proliferation and colony formation abilities of TKE2 cells treated with levobunolol, atenolol, or ICI 118, 551 were investigated by CCK-8 kit and crystal violet staining. The differentiation marker Cytokeratin 3 (CK3), the stem cell markers-Cytokeratin 14 (CK14) and Cytokeratin 19 (CK19), and corneal epithelium regeneration-related signaling including in Ki67 and the phosphorylated epithelial growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were assessed by immunofluorescence staining.

Results

Levobunolol and ICI 118, 551 impaired corneal wound healing, decreased the expressions of CK3, CK14, and CK19 after limbal region scraping in vivo and reduced the migration and proliferation of TKE2 in vitro, whereas atenolol had no significant effect. Moreover, levobunolol and ICI 118, 551 inhibited corneal wound healing by mediating the expression of Ki67, and the phosphorylation of EGFR and ERK1/2 in the limbal and regenerated corneal epithelium.

Conclusion

β-blocker eye drops impaired corneal wound healing by inhibiting the β2AR of limbal stem cells, which decreased corneal epithelial regeneration-related signaling. Therefore, a selective β1AR antagonist might be a good choice for glaucoma treatment to avoid ocular surface damage.
Functional visual acuity after implantation of diffractive extended depth-of-focus intraocular lenses using an echelett optics
Authors: Sakisaka Toshihiro , Minami Keiichiro , Takada Keita , Mori Yosai , Miyata Kazunori
Published: December 2021

Background

The prospective comparative case series aimed to evaluate all-distance visual acuity, contrast sensitivity, and functional visual acuity (FVA) of eyes with diffractive extended depth-of-focus (EDOF) intraocular lenses (IOLs) using an echelett optics and monofocal IOLs with the same platform.

Methods

Diffractive EDOF and monofocal IOLs were implanted in 27 eyes of 27 patients each. At 3 months after implantation, all-distance visual acuities at distances of 0.3, 0.5, 0.7, 1, 2, 3, and 5 m were measured under distance-corrected. Static visual function was also examined using photopic contrast sensitivity and area under the logarithmic contrast sensitivity function (AULCSF). Dynamic visual function was examined with FVA, and mean FVA value, visual maintenance ratio (VMR), mean response time, and number of blinks were evaluated. These outcomes were compared between the two IOLs.

Results

The mean distance-corrected visual acuities were better at distances of 0.7 m or nearer in eyes with EDOF IOLs. There was no difference in the contrast sensitivities (P > 0.22). In the FVA results, no difference was found in mean FVA and VMR (P > 0.68).

Conclusion

The static and dynamic evaluations of postoperative visual functions demonstrated that the visual function of eyes with EDOF IOLs under photopic and distance-corrected conditions was comparable to eyes with monofocal IOLs.
Hordeum murinum aspiration revealed by a pneumopleurocutaneous fistula in a 15-month-old infant
Authors: Richard Nicolas , Paygambar Audrey , Ducou Le Pointe Hubert , Biaz Sarah , Corvol Harriet
Published: December 2021

Background

Hordeum murinum is a specie of grass rarely reported among the aspirated foreign body. It has high tissue penetration power and may cause lung damages.

Case presentation

We report the case of a 15-month-old girl who choke while playing in the grass without any evident cause. This episode was immediately followed by vomiting and coughing with traces of blood. While she was fine during the following week, she relapsed at day (D) 7 with fever. At D10, she was finally hospitalized for signs of respiratory distress. The chest CT-scan revealed a voluminous right sub pleural empyema with an aerial component, responsible for the collapse of the right lower lobe, and complicated by a pneumopleurocutaneous fistula to the right paravertebral muscles. Intravenous antibiotics were prescribed, but no invasive procedure was performed. At D18, the spikelet of a false barley spontaneously externalized through the fistula. Evolution was favorable thereafter with disappearance of the fever and progressive decrease of the biological inflammatory syndrome. The follow-up at 4 months was reassuring, with normal clinical evaluation, and complete regression of the empyema on the chest X-rays.

Conclusions

Hordeum murinum is a rare type of foreign body, and the aspiration often goes unnoticed. In these peculiar cases, CT-scans can be as informative as bronchoscopies, and the evolution is usually favorable after fistulization.
Cost-utility of as-needed ICS-formoterol versus to maintenance ICS in mild to moderate persistent asthma
Authors: Buendía Jefferson Antonio , Patiño Diana Guerrero
Published: December 2021

Background

Recent asthma guidelines, such as the Global Initiative for Asthma (GINA), recommend in adult patients as-needed inhaled corticosteroids (ICS)-formoterol as an alternative to maintenance ICS in mild to moderate persistent asthma. The introduction of these recommendations concerns whether using as-needed budesonide-formoterol would be more cost-effective than to maintenance ICS. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared to short-acting β2-agonist (SABA) reliever therapy in patients with mild asthma.

Methods

A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared to short-acting β2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.

Results

The model suggests a potential gain of 0.37 QALYs and per patient per year on as-needed ICS-formoterol and a reduction in the discounted cost per person-year, of as-needed ICS-formoterol to maintenance ICS, of US$40. This position of dominance of as-needed ICS-formoterol negates the need to calculate an incremental cost-effectiveness ratio. In the deterministic and probabilistic sensitivity analysis, our base‐case results were robust to variations in all assumptions and parameters.

Conclusion

Low-dose budesonide-formoterol as a reliever was cost-effective when added to usual care in patients with mild asthma. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.
Cost-utility of triple versus dual inhaler therapy in moderate to severe asthma
Authors: Buendía Jefferson Antonio , Patiño Diana Guerrero
Published: December 2021

Background

An important proportion of asthma patients remain uncontrolled despite using inhaled corticosteroids and long-acting beta-agonists. Clinical guidelines recommend, in these patients, using add-on long-acting muscarinic antagonists (triple therapy) to treatment with high doses of inhaled corticosteroids-long-acting beta2-agonist (dual therapy). The purpose of this study was to assess the cost-effectiveness of triple therapy versus dual therapy for patients with severe asthma.

Methods

A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. Total costs and QALYS of dual and triple therapy were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.

Results

The model suggests a potential gain of 1.55 QALYs per patient per year on triple therapy with respect to dual therapy. We observed a difference of US$304 in discounted cost per person-year on triple therapy with respect to dual therapy. The incremental cost-effectiveness ratio was US$196 in the probabilistic model. In the sensitivity analysis, our base‐case results were robust to variations in all assumptions and parameters.

Conclusion

In conclusion, triple therapy in patients with moderate-severe asthma was cost-effective. Using triple therapy emerges with our results as an alternative before using oral corticosteroids or biologics, especially in resource-limited settings.
Phytochemical analysis and anticancer activity of Falcaria vulgaris Bernh growing in Moghan plain, northwest of Iran
Authors: Hosseini Kamran , Jasori Sanaz , Delazar Abbas , Asgharian Parina , Tarhriz Vahideh
Published: December 2021

Background

Falcaria vulgaris Bernh among the most important member of Apiaceae family has been used for medical investigation in Iran and some regions in the world. This plant possesses a range of coumarin and flavonoids compounds that have many therapeutic properties such as gastrointestinal and liver diseases, skin ulcers, gastric ulcers, and intestinal inflammation. It has also been found that these compounds lead to cytotoxic effects.

Objective

This study contains concentrates on the cytotoxic effect and induction of apoptosis on cancerous cells (SW-872) through various extracts and essential oil of Falcaria vulgaris Bernh. It considers the volatile compounds of effective samples.

Methods

The shoot of the plant was extracted by the Soxhlet apparatus and its essential oil was taken by the Clevenger apparatus. The cytotoxicity of the samples was evaluated by the MTT method and the mechanism of cancer cell death by flow cytometry and finally, the volatile compounds of essential oils and effective extracts were identified by GC-MS.

Results

The results demonstrated that n-Hexane extract and 40% VLC fraction had the greatest cytotoxic effect on SW-872 cells. While, the most abundant volatile compounds in essential oil and 40% VLC fraction of n-Hexane extract were terpenoid compounds like (+) spathulenol and caryophyllene oxide, in n-Hexane extract tetradecan, and spathulenol were the most, respectively.

Conclusion

The fraction of 40% n-Hexane was in a concentration-dependent manner and significantly with controlling cells inhibited the growth of cancer cells. A plausible explanation could be made to account for this effect. This inhibition was made through induction of apoptosis and due to the presence of effective volatile compounds such as terpenoids and non-terpenoids which could be considered as valuable natural sources for the isolation of anti-cancer compounds.
Drone versus ambulance for blood products transportation: an economic evaluation study
Authors: Zailani M. A. , Azma R. Z. , Aniza I. , Rahana A. R. , Ismail M. S. , Shahnaz I. S. , Chan K. S. , Jamaludin M. , Mahdy Z. A.
Published: December 2021

Background

Medical transportation is an essential step in health care services, and includes ground, air and water transportation. Among the important uses of medical transportation is the delivery of blood products in the event of a clinical emergency. Drone technology is the latest technological advancement that may revolutionize medical transportation globally. Nonetheless, its economic evaluation is scant and insufficient, whilst its cost-effectiveness remains controversial. The aim of this study was to compare the cost-effectiveness of drone transportation versus the ambulance.

Methods

The setting of the study was within a developing nation. An economic evaluation study of drone versus ambulance for emergency blood products transportation between the Sabah Women and Children Hospital (SWACH) and the Queen Elizabeth II Hospital (QEH2) on Borneo Island was conducted using the Cost-Effectiveness Analysis (CEA) technique. The total cost of each mode of transportation was calculated using the Activity Based Costing (ABC) method. Travel time was used as a denominator to estimate the Incremental Cost Effectiveness Ratio (ICER).

Results

For one clinical emergency in SWACH, a round trip of blood products transportation from SWACH to QEH2 costs RM1,266.02 (USD307.09) when using the ambulance, while the drone costs RM1,313.28 (USD319.36). The travel time for the drone was much shorter (18 min) compared to the ambulance (34 min). The Cost-Effectiveness Ratio (CER) of ambulance transportation was RM37.23 (USD9.05) per minute whilst the CER of drone transportation was RM72.96 (USD17.74) per minute. The ICER of drone versus ambulance was − 2.95, implying an increase of RM2.95 in cost for every minute saved using a drone instead of an ambulance.

Conclusion

Although drone transportation of blood products costs more per minute compared to the ambulance, the significantly shorter transport time of the drone offset its cost. Thus, we believe there is good economic potential for drone usage for blood products transportation in developing nations particularly if the drone price decreases and its operational lifespan increases. Our limitation of a non-clinical denominator used in this study leads to the recommendation for use of clinical outcomes in future studies.
Pulmonary lesion subtypes recognition of COVID-19 from radiomics data with three-dimensional texture characterization in computed tomography images
Authors: Li Wei , Cao Yangyong , Yu Kun , Cai Yibo , Huang Feng , Yang Minglei , Xie Weidong
Published: December 2021

Background

The COVID-19 disease is putting unprecedented pressure on the global healthcare system. The CT (computed tomography) examination as a auxiliary confirmed diagnostic method can help clinicians quickly detect lesions locations of COVID-19 once screening by PCR test. Furthermore, the lesion subtypes classification plays a critical role in the consequent treatment decision. Identifying the subtypes of lesions accurately can help doctors discover changes in lesions in time and better assess the severity of COVID-19.

Method

The most four typical lesion subtypes of COVID-19 are discussed in this paper, which are GGO (ground-glass opacity), cord, solid and subsolid. A computer-aided diagnosis approach of lesion subtype is proposed in this paper. The radiomics data of lesions are segmented from COVID-19 patients CT images with diagnosis and lesions annotations by radiologists. Then the three-dimensional texture descriptors are applied on the volume data of lesions as well as shape and first-order features. The massive feature data are selected by HAFS (hybrid adaptive feature selection) algorithm and a classification model is trained at the same time. The classifier is used to predict lesion subtypes as side decision information for radiologists.

Results

There are 3734 lesions extracted from the dataset with 319 patients collection and then 189 radiomics features are obtained finally. The random forest classifier is trained with data augmentation that the number of different subtypes of lesions is imbalanced in initial dataset. The experimental results show that the accuracy of the four subtypes of lesions is (93.06%, 96.84%, 99.58%, and 94.30%), the recall is (95.52%, 91.58%, 95.80% and 80.75%) and the f-score is (93.84%, 92.37%, 95.47%, and 84.42%).

Conclusion

The three-dimensional radiomics features used in this paper can better express the high-level information of COVID-19 lesions in CT slices. HAFS method aggregates the results of multiple feature selection algorithms intersects with traditional methods to filter out redundant features more accurately. After selection, the subtype of COVID-19 lesion can be judged by inputting the features into the RF (random forest) model, which can help clinicians more accurately identify the subtypes of COVID-19 lesions and provide help for further research.
Selective targeting of angiopoietin-like 3 (ANGPTL3) with vupanorsen for the treatment of patients with familial partial lipodystrophy (FPLD): results of a proof-of-concept study
Authors: Foss-Freitas Maria C. , Akinci Baris , Neidert Adam , Bartlett Victoria J. , Hurh Eunju , Karwatowska-Prokopczuk Ewa , Oral Elif A.
Published: December 2021

Background

Familial partial lipodystrophy (FPLD) is a rare disease characterized by selective loss of peripheral subcutaneous fat, associated with dyslipidemia and diabetes mellitus. Reductions in circulating levels of ANGPTL3 are associated with lower triglyceride and other atherogenic lipids, making it an attractive target for treatment of FPLD patients. This proof-of-concept study was conducted to assess the efficacy and safety of targeting ANGPTL3 with vupanorsen in patients with FPLD.

Methods

This was an open-label study. Four patients with FPLD (two with pathogenic variants in LMNA gene, and two with no causative genetic variant), diabetes (HbA1c ≥ 7.0 % and ≤ 12 %), hypertriglyceridemia (≥ 500 mg/dL), and hepatic steatosis (hepatic fat fraction, HFF ≥ 6.4 %) were included. Patients received vupanorsen subcutaneously at a dose of 20 mg weekly for 26 weeks. The primary endpoint was the percent change from baseline in fasting triglycerides at Week 27. Other endpoints analyzed at the same time point included changes in ANGPTL3, fasting lipids and lipoproteins, insulin secretion/sensitivity, postprandial lipids, and glycemic changes in response to a mixed meal test, HFF measured by MRI, and body composition measured by dual-energy absorptiometry (DEXA).

Results

Baseline mean ± SD fasting triglyceride level was 9.24 ± 4.9 mmol/L (817.8 ± 431.9 mg/dL). Treatment resulted in reduction in fasting levels of triglycerides by 59.9 %, ANGPTL3 by 54.7 %, and in several other lipoproteins/lipids, including very low-density lipoprotein cholesterol by 53.5 %, non-high-density lipoprotein cholesterol by 20.9 %, and free fatty acids (FFA) by 41.7 %. The area under the curve for postprandial triglycerides, FFA, and glucose was reduced by 60 %, 32 %, and 14 %, respectively. Treatment with vupanorsen also resulted in 55 % reduction in adipose tissue insulin resistance index, while other insulin sensitivity indices and HbA1c levels were not changed. Additional investigations into HFF and DEXA parameters suggested dynamic changes in fat partitioning during treatment. Adverse events observed were related to common serious complications associated with diabetes and FPLD. Vupanorsen was well tolerated, and there was no effect on platelet count.

Conclusions

Although limited, these results suggest that targeting ANGPTL3 with vupanorsen could address several metabolic abnormalities in patients with FPLD.
Discordance between the triglyceride glucose index and HOMA-IR in incident albuminuria: a cohort study from China
Authors: Gao Wei , Wang Jialu , Chen Yan , Qiao Hongmei , Qian Xiaozhong , Xin Zhuojun , Zhao Zhiyun , Wang Tiange , Xu Yu , Xu Min , Bi Yufang , Li Mian , Gao Jinli
Published: December 2021

Background

To date, there have no study comparing the associations between TyG index and HOMA-IR on the risk of incident albuminuria. Accordingly, the objective of the present study is to use discordance analysis to evaluate the diverse associations between TyG index and HOMA-IR on the risk of incident albuminuria.

Methods

A community-based prospective cohort study was performed with 2446 Chinese adults. We categorized participants into 4 concordance or discordance groups. Discordance was defined as a TyG index equal to or greater than the upper quartile and HOMA-IR less than the upper quartile, or vice versa.

Results

During a median follow-up period of 3.9 years, 203 of 2446 participants developed incident albuminuria (8.3%). In the multivariable logistic analyses, the high TyG index tertile group was associated with a 1.71-fold (95% confidence interval (CI) 1.07–2.72) higher risk of incident albuminuria, comparing with the low tertile group. Participants in TyG (+) & HOMA-IR (−) group had a greater risk of incident albuminuria compared with those in TyG (−) & HOMA-IR (−) group after multivariate adjustment. Subgroup analyses showed that low HOMA-IR and discordantly high TyG index was closely related to a highest risk of incident albuminuria in cardiovascular metabolic disorder subjects.

Conclusions

Participants with a discordantly high TyG index had a significantly greater risk of incident albuminuria, especially in metabolic dysfunction subjects. The TyG index might be a better predictor of early stage of chronic kidney disease than HOMA-IR for subjects with metabolic abnormality.
The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance
Authors: Kollar Branislav , Siarnik Pavel , Hluchanova Alzbeta , Klobucnikova Katarina , Mucska Imrich , Turcani Peter , Paduchova Zuzana , Katrencikova Barbora , Janubova Maria , Konarikova Katarina , Argalasova Lubica , Oravec Stanislav , Zitnanova Ingrid
Published: December 2021

Background

Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides.

Methods

The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically.

Results

OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3–7 and HDL8–10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals.

Conclusion

The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.
Nanofiber-mediated sequential photothermal antibacteria and macrophage polarization for healing MRSA-infected diabetic wounds
Authors: Xu Zhou , Deng Bin , Wang Xuewen , Yu Jie , Xu Zhuobin , Liu Penggang , Liu Caihong , Cai Yuan , Wang Fei , Zong Rongling , Chen Zhiling , Xing Hua , Chen Gang
Published: December 2021

Background

Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes.

Methods

We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds.

Results

The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation.

Conclusion

Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy.

Graphical abstract