bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of patients’ knowledge about their medications: A cross-sectional study in Qassim region, Saudi Arabia
Authors: Alfadl Abubakr Abdelraouf , Anaam Mohammed Saif , Alhassun Musaad Saleh , Albuaymi Yazeed Rasheed , Alrehaili Faris Moallath , Alsikhan Rawan Saleh
Published: April 2023

Background:

To authors’ knowledge, in Saudi Arabia, information regarding patients’ knowledge about their medications is lacking.

Objectives:

This study aimed to fill this literature gap by assessing patients’ knowledge and perceptions about their medications.

Design:

To achieve the objective of the study, a cross-sectional survey was conducted outside community pharmacies in Qassim region through an exit interview with patients after getting their prescriptions filled or refilled.

Methods:

A convenient sample of patients was chosen based on acceptance to participate. A form was prepared based on the core and complementary medicines use indicators for evaluation of medicines use in healthcare settings developed by the World Health Organization (WHO).

Results:

Four hundred forty-three forms were completed. A total of 70% of the indicators of patients’ knowledge about their medications were found to be satisfactory, and a total of 89% of the patients were found to have positive perceptions about safety and effectiveness of their medications.

Conclusion:

Overall, patients’ knowledge about their medications was found to be reasonable with exception of the area “information about precautions and possible side effects” which had shown poor patients’ knowledge.
RNA interference therapy in acute hepatic porphyrias
Authors: Yasuda Makiko , Keel Siobán , Balwani Manisha
Published: April 2023

The acute hepatic porphyrias (AHPs) are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks precipitated by factors that upregulate hepatic 5-aminolevulinic acid synthase 1 (ALAS1) activity. Induction of hepatic ALAS1 leads to the accumulation of porphyrin precursors, in particular 5-aminolevulinic acid (ALA), which is thought to be the neurotoxic mediator leading to acute attack symptoms such as severe abdominal pain and autonomic dysfunction. Patients may also develop debilitating chronic symptoms and long-term medical complications, including kidney disease and an increased risk of hepatocellular carcinoma. Exogenous heme is the historical treatment for attacks and exerts its therapeutic effect by inhibiting hepatic ALAS1 activity. The pathophysiology of acute attacks provided the rationale to develop an RNA interference therapeutic that suppresses hepatic ALAS1 expression. Givosiran is a subcutaneously administered N-acetylgalactosamine–conjugated small interfering RNA against ALAS1 that is taken up nearly exclusively by hepatocytes via the asialoglycoprotein receptor. Clinical trials established that the continuous suppression of hepatic ALAS1 mRNA via monthly givosiran administration effectively reduced urinary ALA and porphobilinogen levels and acute attack rates and improved quality of life. Common side effects include injection site reactions and increases in liver enzymes and creatinine. Givosiran was approved by the US Food and Drug Administration and European Medicines Agency in 2019 and 2020, respectively, for the treatment of patients with AHP. Although givosiran has the potential to decrease the risk of chronic complications, long-term data on the safety and effects of sustained ALAS1 suppression in patients with AHP are lacking.
A fixed-duration immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial
Authors: Michallet Anne-Sophie , Letestu Rémi , Le Garff-Tavernier Magali , Campos Lydia , Ticchioni Michel , Dilhuydy Marie-Sarah , Morisset Stephane , Rouille Valérie , Mahé Béatrice , Laribi Kamel , Villemagne Bruno , Ferrant Emmanuelle , Tournilhac Olivier , Delmer Alain , Molina Lysiane , Leblond Véronique , Tomowiak Cécile , de Guibert Sophie , Orsini-Piocelle Frederique , Banos Anne , Carassou Philippe , Cartron Guillaume , Fornecker Luc Mathieu , Ysebaert Loic , Dartigeas Caroline , Truchan-Graczyk Margot , Vilque Jean-Pierre , Schleinitz Thérèse Aurran , Cymbalista Florence , Leprêtre Stéphane , Lévy Vincent , Nguyen-Khac Florence , Feugier Pierre
Published: April 2023

In previously untreated, medically fit patients with chronic lymphocytic leukemia (CLL), research is focused on developing fixed-duration strategies to improve long-term outcomes while sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach in which after obinutuzumab-ibrutinib induction for 9 months, patients (n = 10) in complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) <0.01% continued only ibrutinib 420 mg/day for 6 additional months (I arm), whereas the majority (n = 115) received up to 4 cycles of fludarabine/cyclophosphamide-obinutuzumab 1000 mg alongside the ibrutinib (I-FCG arm). Primary analysis at month 16 showed that 84 of 135 (62.2%) patients enrolled achieved CR with a BM MRD <0.01%. Here, we report follow-up at median 63 months. Peripheral blood (PB) MRD was assessed 6 monthly beyond the end of treatment using a highly sensitive (10-6) flow cytometry technique. In the I-FCG arm, the PB MRD <0.01% rate (low-level positive <0.01% or undetectable with limit of detection ≤10-4) in evaluable patients was still 92.5% (74/80) at month 40 and 80.6% (50/62) at month 64. No differences in the PB MRD status were apparent per to the IGHV mutational status. In the overall population, 4-year progression-free and overall survival rates were 95.5% and 96.2%, respectively. Twelve deaths occurred overall. Fourteen serious adverse events occurred beyond the end of treatment. Thus, our fixed-duration immunochemotherapy approach produced deep and sustained PB MRD responses, high survival rates, and low long-term toxicity. A randomized trial is needed to compare our immunochemotherapy approach with a chemotherapy-free strategy. This trial was registered at www.clinicaltrials.gov as #NCT02666898.
Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions
Authors: Major Ajay , Yu Jovian , Shukla Navika , Che Yan , Karrison Theodore G. , Treitman Rachel , Kamdar Manali K. , Haverkos Bradley M. , Godfrey James , Babcook Melissa A. , Voorhees Timothy J. , Carlson Sophie , Gaut Daria , Oliai Caspian , Romancik Jason T. , Winter Allison M. , Hill Brian T. , Bansal Radhika , Villasboas Bisneto Jose C. , Nizamuddin Imran A. , Karmali Reem , Fitzgerald Lindsey A. , Stephens Deborah M. , Pophali Priyanka A. , Trabolsi Asaad , Schatz Jonathan H. , Hu Marie , Bachanova Veronika , Slade Michael J. , Singh Nathan , Ahmed Nausheen , McGuirk Joseph P. , Bishop Michael R. , Riedell Peter A. , Kline Justin
Published: April 2023

Checkpoint inhibitor (CPI) therapy with anti–PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 vs 51 days) and OS (387 vs 131 days) were significantly longer in patients with late (>180 days) vs early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, commonly because of progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post–CAR-T outcomes.
Dynamic susceptibility of Fe3O4 nanotubes
Authors: Pusiol Enzo Fabrizio , Saavedra Eduardo , Pereira Alejandro , Palma Juan Luis , Bajales Noelia , Escrig Juan
Published: April 2023

In this work we performed a detailed numerical analysis to investigate the dynamic susceptibility of 1000 nm long Fe3O4 nanotubes by varying the diameter, the tube wall thickness and the magnitude of the external magnetic field applied along the tube axis. We found two well-defined modes, one of low frequency associated with the caps of the nanotubes, and another of high frequency associated with the central area of the nanotubes, which can be controlled by varying the geometry of the tubes or the external magnetic field to which they are subjected. These results allow us to suggest the use of these nanotubes in applications that require controlling the resonant frequency in the GHz range.
Automatic block-wise genotype-phenotype association detection based on hidden Markov model
Authors: Du Jin , Wang Chaojie , Wang Lijun , Mao Shanjun , Zhu Bencong , Li Zheng , Fan Xiaodan
Published: April 2023

Background

For detecting genotype-phenotype association from case–control single nucleotide polymorphism (SNP) data, one class of methods relies on testing each genomic variant site individually. However, this approach ignores the tendency for associated variant sites to be spatially clustered instead of uniformly distributed along the genome. Therefore, a more recent class of methods looks for blocks of influential variant sites. Unfortunately, existing such methods either assume prior knowledge of the blocks, or rely on ad hoc moving windows. A principled method is needed to automatically detect genomic variant blocks which are associated with the phenotype.

Results

In this paper, we introduce an automatic block-wise Genome-Wide Association Study (GWAS) method based on Hidden Markov model. Using case–control SNP data as input, our method detects the number of blocks associated with the phenotype and the locations of the blocks. Correspondingly, the minor allele of each variate site will be classified as having negative influence, no influence or positive influence on the phenotype. We evaluated our method using both datasets simulated from our model and datasets from a block model different from ours, and compared the performance with other methods. These included both simple methods based on the Fisher’s exact test, applied site-by-site, as well as more complex methods built into the recent Zoom-Focus Algorithm. Across all simulations, our method consistently outperformed the comparisons.

Conclusions

With its demonstrated better performance, we expect our algorithm for detecting influential variant sites may help find more accurate signals across a wide range of case–control GWAS.
Risk factors associated with home care safety for older people with dementia: family caregivers’ perspectives
Authors: Yin Guo , Lin Siting , Chen Linghui
Published: April 2023

Background

Many older people with dementia currently prefer home care; however, homes are neither professionally designed nor regulated like health care facilities, and home care is more prone to safety incidents. Many studies have examined home care safety for older people with dementia. However, factors contributing to safety incidents in home care have not been adequately considered. This study explored the risk factors for home care safety for older people with dementia based on the perspective of family caregivers.

Methods

This study used a qualitative research approach; a total of 24 family caregivers were interviewed face-to-face and semi-structured from February 2022 to May 2022, and the Colaizzi seven-step phenomenological research method was used to analyze the data and refine the themes.

Results

Safety risks in home care for older people with dementia stem from five areas: poor health of older people with dementia, dementia symptoms, unsafe home environment, the insufficient caring ability of family caregivers, and lack of safety awareness of family caregivers.

Conclusion

The risk factors for home care safety for older people with dementia are complex. And as the primary caregivers of older people with dementia, the caregiving ability and safety awareness of family caregivers primarily determine the safety of home care for older people with dementia. Therefore, when addressing home care safety for older people with dementia, the focus should be on providing targeted education programs and support services for family caregivers of older people with dementia.
Healthcare expenditure and technology use in pediatric diabetes care
Authors: de Vries Silvia A. G. , Bak Jessica C. G. , Verheugt Carianne L. , Stangenberger Vincent A. , Mul Dick , Wouters Michel W. J. M. , Nieuwdorp Max , Sas Theo C. J.
Published: April 2023

Background

Diabetes mellitus is one of the most common chronic diseases in childhood. With more advanced care options including ever-evolving technology, allocation of resources becomes increasingly important to guarantee equal care for all. Therefore, we investigated healthcare resource utilization, hospital costs, and its determinants in Dutch children with diabetes.

Methods

We conducted a retrospective, observational analysis with hospital claims data of 5,474 children with diabetes mellitus treated in 64 hospitals across the Netherlands between 2019–2020.

Results

Total hospital costs were €33,002,652 per year, and most of these costs were diabetes-associated (€28,151,381; 85.3%). Mean annual diabetes costs were €5,143 per child, and treatment-related costs determined 61.8%. Diabetes technology significantly increased yearly diabetes costs compared to no technology: insulin pumps € 4,759 (28.7% of children), Real-Time Continuous Glucose Monitoring € 7,259 (2.1% of children), and the combination of these treatment modalities € 9,579 (27.3% of children). Technology use increased treatment costs significantly (5.9 – 15.3 times), but lower all-cause hospitalisation rates were observed. In all age groups, diabetes technology use influenced healthcare consumption, yet in adolescence usage decreased and consumption patterns changed.

Conclusions

These findings suggest that contemporary hospital costs of children with diabetes of all ages are driven primarily by the treatment of diabetes, with technology use as an important additive factor. The expected rise in technology use in the near future underlines the importance of insight into resource use and cost-effectiveness studies to evaluate if improved outcomes balance out these short-term costs of modern technology.
Circulating levels of adropin and diabetes: a systematic review and meta-analysis of observational studies
Authors: Soltani Sepideh , Beigrezaei Sara , Malekahmadi Mahsa , Clark Cain C. T. , Abdollahi Shima
Published: April 2023

Objective

Adropin, a newly identified regulatory protein has garnered attention given its potential role in metabolism regulation, especially glucose metabolism and insulin resistance. However, studies on the association between adropin and type 2 diabetes mellitus (T2DM) are equivocal. The aim of this study is to assess the association between serum adropin levels and T2DM using a systematic review and meta-analysis of observational studies.

Methods

PubMed, Scopus, ISI Web of science, and Google Scholar were searched, up to August 2022, for studies that reported the association between serum levels of adropin in adults with T2DM compared to a control group without diabetes. A random-effect model was used to compute the pooled weighted mean difference (WMD) with 95% confidence intervals (CI).

Results

Meta-analysis of 15 studies (n = 2813 participants) revealed that the serum adropin concentrations were significantly lower in patients with T2DM compared with the control group (WMD= -0.60 ng/mL, 95% CI: -0.70 to -0.49; I2 = 99.5%). Subgroup analysis also found lower concentration of adropin in patients with T2DM who were otherwise healthy compared to a control group (n = 9; WMD=-0.04 ng/ml, 95% CI= -0.06 to -0.01, p = 0.002; I2 = 96.4).

Conclusions

Our study showed adropin levels are lower in patients with diabetes compared to a control group without diabetes. However, the limitations of observational studies challenge the validity of the results, and further investigations are needed to confirm the veracity of these findings and additionally explore possible mechanisms.
Learning needs of nursing postgraduates in Southwest China based on Hutchinson’s learning needs theory: a qualitative research
Authors: Zhang Suofei , Ma Huijuan , Zhu Xiaoli , Niu Aifang , Luo Yu
Published: April 2023

Background

The process of education is mutual. The learning needs of students need to be paid attention to and can affect the learning outcome. In order to make nursing postgraduates’ curriculum better, meet the learning needs of students, and help to achieve the learning objectives of students, this study based on Hutchinson’s learning needs theory, aims to collect the learning experience of nursing graduates, as well as the gap between learning needs and target needs, and explore the benefits and barriers of nursing graduates in the curriculum learning. It may provide beneficial reference for further optimizing teaching content and improving teaching methods.

Methods

This study was designed as a qualitative research. Purposive sampling was used to recruit 17 nursing postgraduates in the only two universities in Chongqing, Southwest China, 2021. Semi-structured, in-depth individual interviews were conducted to explore how they subjectively experience the benefits and demands of the professional curriculum. Data was analyzed using Colaizzi’s seven-step analysis.

Results

Three main themes “clear learning cognition and goals,” “positive learning attitude,” and “the gap between learning goals and actual needs” were identified from the original data. Respectively, Subthemes concerning the first theme included “improve scientific research capabilities, enlighten thinking and broaden your horizons, and learn new knowledge and new skills.” Subthemes of the second theme were “improve abilities in practice and actively seek diversification of course content and format.” Subthemes of the third theme included “the course has a certain depth and breadth, but the course study does not meet the needs of scientific research, the course contents are theoretical, not knowing how to use the research method in certain conditions.”

Conclusions

The learning needs of nursing postgraduates in Southwest China could be divided into two parts: benefits and barriers, among which the benefits were participants had clear learning goals and positive learning attitudes. When curriculum could not meet their needs, they actively sought methods (e.g., networks or off-campus resources) to close the gap between those needs and their goals. Follow-up educators should focus on learning needs and build curricula by optimizing the contents and methods of existing teaching resources.
Newly qualified registered nurses’ and midwives’ experiences from rural health district placement in Namibia
Authors: Katuta Martha N , Nuuyoma Vistolina
Published: April 2023

Background

The transition period for newly qualified registered nurses/midwives (NQRN/Ms) is a fundamental phase in their career. Yet, transition experiences have been studied mostly within urban and/or specialised healthcare settings in high-resource countries. This study aimed to explore and describe the experiences of NQRN/Ms in a rural health district in Namibia.

Methods

A qualitative, descriptive, explorative, and contextual design was followed. The sample consisted of eight participants who were purposively selected. Data were collected via in-depth individual interviews and analysed following a reflexive thematic analysis. The researchers were guided by Lincoln and Guba’s strategies for establishing trustworthiness.

Findings

Themes conceptualised from the analysis include encounters with rural community members; encounters with colleagues; staffing, management, and supervision; shortage of resources; poor infrastructure; unreliable communication networks; and the lack of social life.

Conclusion

The NQRN/Ms had mixed experiences related to a variety of aspects such as social life, resources, colleagues and community members. These findings can be used to improve undergraduate nursing curricula, as well as to create graduate job preparation workshops and support networks.
Back to the roots, desiccation and radiation resistances are ancestral characters in bdelloid rotifers
Authors: Hespeels Boris , Fontaneto Diego , Cornet Valérie , Penninckx Sébastien , Berthe Jérémy , Bruneau Lucie , Larrick James W. , Rapport Eloïse , Bailly Jérémie , Debortoli Nicolas , Iakovenko Nataliia , Janko Karel , Heuskin Anne-Catherine , Lucas Stéphane , Hallet Bernard , Van Doninck Karine
Published: April 2023

Background

Bdelloid rotifers are micro-invertebrates distributed worldwide, from temperate latitudes to the most extreme areas of the planet like Antarctica or the Atacama Desert. They have colonized any habitat where liquid water is temporarily available, including terrestrial environments such as soils, mosses, and lichens, tolerating desiccation and other types of stress such as high doses of ionizing radiation (IR). It was hypothesized that bdelloid desiccation and radiation resistance may be attributed to their potential ability to repair DNA double-strand breaks (DSBs). Here, these properties are investigated and compared among nine bdelloid species collected from both mild and harsh habitats, addressing the correlation between the ability of bdelloid rotifers to survive desiccation and their capacity to repair massive DNA breakage in a phylogenetically explicit context. Our research includes both specimens isolated from habitats that experience frequent desiccation (at least 1 time per generation), and individuals sampled from habitats that rarely or never experienced desiccation.

Results

Our analysis reveals that DNA repair prevails in somatic cells of both desiccation-tolerant and desiccation-sensitive bdelloid species after exposure to X-ray radiation. Species belonging to both categories are able to withstand high doses of ionizing radiation, up to 1000 Gy, without experiencing any negative effects on their survival. However, the fertility of two desiccation-sensitive species,Rotaria macruraandRotaria rotatoria, was more severely impacted by low doses of radiation than that of desiccation-resistant species. Surprisingly, the radioresistance of desiccation-resistant species is not related to features of their original habitat. Indeed, bdelloids isolated from Atacama Desert or Antarctica were not characterized by a higher radioresistance than species found in more temperate environments.

Conclusions

Tolerance to desiccation and radiation are supported as ancestral features of bdelloid rotifers, with a group of species of the genus Rotaria having lost this trait after colonizing permanent water habitats. Together, our results provide a comprehensive overview of the evolution of desiccation and radiation resistance among bdelloid rotifers.
Increased iron deposition in nucleus accumbens associated with disease progression and chronicity in migraine
Authors: Xu Xiaopei , Zhou Mengting , Wu Xiao , Zhao Fangling , Luo Xiao , Li Kaicheng , Zeng Qingze , He Jiahui , Cheng Hongrong , Guan Xiaojun , Huang Peiyu , Zhang Minming , Liu Kaiming
Published: April 2023

Background

Migraine is one of the world’s most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments.

Methods

A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well.

Results

Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI.

Conclusions

These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine.

Trial registration

ClinicalTrials.gov, number NCT04939922.
Malaria control and elimination in Kenya: economy-wide benefits and regional disparities
Authors: Elnour Zuhal , Grethe Harald , Siddig Khalid , Munga Stephen
Published: April 2023

Background

Malaria remains a public health problem in Kenya despite several concerted control efforts. Empirical evidence regarding malaria effects in Kenya suggests that the disease imposes substantial economic costs, jeopardizing the achievement of sustainable development goals. The Kenya Malaria Strategy (2019–2023), which is currently being implemented, is one of several sequential malaria control and elimination strategies. The strategy targets reducing malaria incidences and deaths by 75% of the 2016 levels by 2023 through spending around Kenyan Shillings 61.9 billion over 5 years. This paper assesses the economy-wide implications of implementing this strategy.

Methods

An economy-wide simulation model is calibrated to a comprehensive 2019 database for Kenya, considering different epidemiological zones. Two scenarios are simulated with the model. The first scenario (GOVT) simulates the annual costs of implementing the Kenya Malaria Strategy by increasing government expenditure on malaria control and elimination programmes. The second scenario (LABOR) reduces malaria incidences by 75% in all epidemiological malaria zones without accounting for the changes in government expenditure, which translates into rising the household labour endowment (benefits of the strategy).

Results

Implementing the Kenya Malaria Strategy (2019–2023) enhances gross domestic product at the end of the strategy implementation period due to more available labour. In the short term, government health expenditure (direct malaria costs) increases significantly, which is critical in controlling and eliminating malaria. Expanding the health sector raises the demand for production factors, such as labour and capital. The prices for these factors rise, boosting producer and consumer prices of non-health-related products. Consequently, household welfare decreases during the strategy implementation period. In the long run, household labour endowment increases due to reduced malaria incidences and deaths (indirect malaria costs). However, the size of the effects varies across malaria epidemiological and agroecological zones depending on malaria prevalence and factor ownership.

Conclusions

This paper provides policymakers with an ex-ante assessment of the implications of malaria control and elimination on household welfare across various malaria epidemiological zones. These insights assist in developing and implementing related policy measures that reduce the undesirable effects in the short run. Besides, the paper supports an economically beneficial long-term malaria control and elimination effect.
Genotyping of Anopheles mosquito blood meals reveals nonrandom human host selection: implications for human-to-mosquito Plasmodium falciparum transmission
Authors: Mbewe Rex B. , Keven John B. , Mangani Charles , Wilson Mark L. , Mzilahowa Themba , Mathanga Don P. , Valim Clarissa , Laufer Miriam K. , Walker Edward D. , Cohee Lauren M.
Published: April 2023

Background

Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to human-to-mosquito transmission than others. Infection prevalence peaks in school-age children, but it is not known how often they are fed upon. Genotypic profiling of human blood permits identification of individual humans who were bitten. The present investigation used this method to estimate which human demographic groups were most responsible for transmitting malaria parasites to Anopheles mosquitoes. It was hypothesized that school-age children contribute more than other demographic groups to human-to-mosquito malaria transmission.

Methods

In a region of moderate-to-high malaria incidence in southeastern Malawi, randomly selected households were surveyed to collect human demographic information and blood samples. Blood-fed, female Anopheles mosquitoes were sampled indoors from the same houses. Genomic DNA from human blood samples and mosquito blood meals of human origin was genotyped using 24 microsatellite loci. The resultant genotypes were matched to identify which individual humans were sources of blood meals. In addition, Plasmodium falciparum DNA in mosquito abdomens was detected with polymerase chain reaction. The combined results were used to identify which humans were most frequently bitten, and the P. falciparum infection prevalence in mosquitoes that resulted from these blood meals.

Results

Anopheles females selected human hosts non-randomly and fed on more than one human in 9% of the blood meals. Few humans contributed most of the blood meals to the Anopheles vector population. Children ≤ 5 years old were under-represented in mosquito blood meals while older males (31–75 years old) were over-represented. However, the largest number of malaria-infected blood meals was from school age children (6–15 years old).

Conclusions

The results support the hypothesis that humans aged 6–15 years are the most important demographic group contributing to the transmission of P. falciparum to the Anopheles mosquito vectors. This conclusion suggests that malaria control and prevention programmes should enhance efforts targeting school-age children and males.
CaCO3 powder-mediated biomineralization of antigen nanosponges synergize with PD-1 blockade to potentiate anti-tumor immunity
Authors: Su Runping , Gu Jingjing , Sun Juanjuan , Zang Jie , Zhao Yuge , Zhang Tingting , Chen Yingna , Chong Gaowei , Yin Weimin , Zheng Xiao , Liu Bingbing , Huang Li , Ruan Shuangrong , Dong Haiqing , Li Yan , Li Yongyong
Published: April 2023

Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of “antigen multi-copy display” and “calcium carbonate (CaCO3) biomineralization” to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4+ T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.
Remodeling the hepatic fibrotic microenvironment with emerging nanotherapeutics: a comprehensive review
Authors: Zhao Xingtao , Amevor Felix Kwame , Xue Xinyan , Wang Cheng , Cui Zhifu , Dai Shu , Peng Cheng , Li Yunxia
Published: April 2023

Liver fibrosis could be the last hope for treating liver cancer and remodeling of the hepatic microenvironment has emerged as a strategy to promote the ablation of liver fibrosis. In recent years, especially with the rapid development of nanomedicine, hepatic microenvironment therapy has been widely researched in studies concerning liver cancer and fibrosis. In this comprehensive review, we summarized recent advances in nano therapy-based remodeling of the hepatic microenvironment. Firstly, we discussed novel strategies for regulatory immune suppression caused by capillarization of liver sinusoidal endothelial cells (LSECs) and macrophage polarization. Furthermore, metabolic reprogramming and extracellular matrix (ECM) deposition are caused by the activation of hepatic stellate cells (HSCs). In addition, recent advances in ROS, hypoxia, and impaired vascular remodeling in the hepatic fibrotic microenvironment due to ECM deposition have also been summarized. Finally, emerging nanotherapeutic approaches based on correlated signals were discussed in this review. We have proposed novel strategies such as engineered nanotherapeutics targeting antigen-presenting cells (APCs) or direct targeting T cells in liver fibrotic immunotherapy to be used in preventing liver fibrosis. In summary, this comprehensive review illustrated the opportunities in drug targeting and nanomedicine, and the current challenges to be addressed.

Graphical Abstract
An optimized circular polymerase extension reaction-based method for functional analysis of SARS-CoV-2
Authors: Liu GuanQun , Gack Michaela U.
Published: April 2023

Background

Reverse genetics systems have been crucial for studying specific viral genes and their relevance in the virus lifecycle, and become important tools for the rational attenuation of viruses and thereby for vaccine design. Recent rapid progress has been made in the establishment of reverse genetics systems for functional analysis of SARS-CoV-2, a coronavirus that causes the ongoing COVID-19 pandemic that has resulted in detrimental public health and economic burden. Among the different reverse genetics approaches, circular polymerase extension reaction (CPER) has become one of the leading methodologies to generate recombinant SARS-CoV-2 infectious clones. Although CPER has greatly facilitated SARS-CoV-2 analysis, it still has certain intrinsic limitations that impede the efficiency and robustness of virus rescue.

Results

We developed an optimized CPER methodology which, through the use of a modified linker plasmid and by performing DNA nick ligation and direct transfection of permissive cells, overcomes certain intrinsic limitations of the ‘traditional’ CPER approaches for SARS-CoV-2, allowing for efficient virus rescue.

Conclusions

The herein described optimized CPER system may facilitate research studies to assess the contribution of SARS-CoV-2 genes and individual motifs or residues to virus replication, pathogenesis and immune escape, and may also be adapted to other viruses.
The 100 most cited papers on thymoma: a bibliometric analysis
Authors: Liu Lei , Zhang Jiaqi , Wang Guige , Zhao Ke , Guo Chao , Huang Cheng , Li Shanqing , Chen Yeye
Published: April 2023

Objectives

The aim of this bibliometric analysis was twofold: to identify the 100 most cited research articles on thymoma and to highlight future research opportunities in light of past and current research efforts.

Methods

The Web of Science database was queried to identify the 100 most cited articles on thymoma. Imformations relevant to scientific research were extracted and analyzed: first author, journal, impact factor, type of article, year of publication, country, organization and keywords.

Results

The publication year of the top 100 most cited articles ranged from 1981 to 2018, and the number of citations ranged from 97 to 1182. Most of the included articles are original (75/100) and are mainly retrospective studies (52/75). The United States has the most published articles and citations, and the Annals of Thoracic Surgery is the most sourced journal (n = 16). Through VOSviewer analysis, high-density keywords mainly come from thymic carcinoma/invasive thymoma management, immune-related diseases, and laboratory research.

Conclusions

To our knowledge, this is the first bibliometric study on thymoma. We found most of the top 100 most cited articles are original and retrospective research. The United States has the published and cited works. Presently, the hot keywords for thymoma research has gradually tilted towards immune-related diseases and laboratory research.
Seasonal and daily variations in the occurence and outcomes of acute Stanford type A dissections: a retrospective single-center study
Authors: Lin Qinmei , Wu Qingsong , Chen Xiaodong , Chen Xingfeng , Xie Linfeng , Chen Liangwan
Published: April 2023

Background

To investigate the seasonal, monthly, and daily distributions of the incidence of Stanford type-A acute aortic dissection (TAAAD) and identify seasonality in the duration of hospital stay and in-hospital mortality of TAAAD in south-eastern China.

Methods

We enrolled patients diagnosed with TAAAD between 1 June 2017 and 31 May 2021. Participants were divided into seasonal, monthly, and daily groups according to the need for analysis. Analysis of variance was applied to compare the number of TAAAD in different seasons, months, and days. χ2 test was used to compare in-hospital mortality among the four groups. Non-parametric methods were used for all comparisons of the duration of hospital stay. Univariate logistic and multivariable logistic regression analyses were performed to assess the duration of hospital stay.

Results

Of the 485 patients, 154 were diagnosed in winter (31.8%), 115 in spring (23.7%), 73 in summer (15.1%), and 143 in autumn (29.5%). The daily, monthly, and seasonal distributions of TAAAD were significantly different (P = 0.04, P < 0.01, and P < 0.01, respectively). This study did not identify any significant decrease in maximal, mean, or minimum temperatures between the three days before TAAAD and the day of TAAAD. No seasonal variations associated with in-hospital mortality was observed (P = 0.89). However, significant differences were observed in the seasonal distribution of the duration of hospital stay for TAAAD [winter was 17.0 (4.0–24.0) days, spring was 20.0 (14.0–29.0) days, summer was 20.0 (12.5–31.0) days, and autumn was 20.0 (13.0–30.0) days, P < 0.01]. Multiple factor analysis showed that winter was the independent risk factor for the increased duration of hospital stay. The odds ratio for winter was 2.21 (1.46, 3.33, P < 0.01).

Conclusions

Our study confirmed that the incidence of TAAAD exhibits seasonal, monthly, and daily variations in south-eastern China. Moreover, the daily incidence of TAAAD is higher on weekdays than that on weekends.
Fibrinogen is an independent preoperative predictor of hospital length of stay among patients undergoing coronary artery bypass grafting
Authors: Huang Chunsheng , Zhang Wenyuan , Chen Xiaofei , Xu Xia , Qiu Jun , Pan Zhihao
Published: April 2023

Objective

This study aims to examine the impact of preoperative fibrinogen concentration on the short-term outcomes and hospital length of stay (LOS) of patients undergoing Coronary Artery Bypass Grafting (CABG).

Methods

Between January 2010 and June 2022, a retrospective analysis comprised 633 patients who sequentially received isolated, primary CABG. These patients were categorized into normal fibrinogen group (fibrinogen < 3.5 g/L) and high fibrinogen group (fibrinogen ≥ 3.5 g/L) according to preoperative fibrinogen concentration. The primary outcome was LOS. To correct for confounding and investigate the effect of preoperative fibrinogen concentration on the short-term outcomes and LOS, we employed propensity score matching (PSM). The correlation between fibriongen concentration and LOS in subgroups was examined using subgroup analysis.

Results

We categorized 344 and 289 patients in the “normal fibrinogen group” and “high fibrinogen group”, respectively. After PSM, compared to the normal fibrinogen group, the high fibrinogen group had a longer LOS [12.00 (9.00–15.00) vs. 13.00 (10.00–16.00), P = 0.028] and higher incidence of postoperative renal impairment [49 (22.1%) vs. 72 (32.4%), P = 0.014]. Cardiopulmonary bypass (CPB) or non-CPB CABG patients showed similar correlations between various fibrinogen concentrations and LOS, according to subgroup analyses.

Conclusions

Fibrinogen is an independent preoperative predictor of both the LOS and the postoperative renal impairment that occurs after CABG. Patients with high preoperative fibrinogen concentration had a higher incidence of postoperative renal impairment and a longer LOS, emphasizing the significance of preoperative fibrinogen management.
Grading criteria for venous invasion in thoracic esophageal squamous cell carcinoma
Authors: Wang An , Liu Xiaojia , Lu Lu , Wang Shaohua , Chen Xiaofeng
Published: April 2023

Background

Venous invasion (VI) is an adverse prognostic indicator in esophageal squamous cell carcinoma. However, grading criteria for venous invasion in thoracic esophageal squamous cell carcinoma (ESCC) have not been established.

Methods

We enrolled 598 thoracic ESCC patients from 2005 to 2017. We detected the presence of venous invasion using the hematoxylin and eosin (H&E)-staining method and evaluated the VI grade on the basis of the number and maximal size of the involved veins. The degree of VI was classified as either 0, V1, V2, or V3, according to the combination of V-number and V-size.

Results

The 1-year, 3-year and 5-year disease-free survival rates were 79.7%, 64.7% and 61.2%, respectively. Multivariate analysis demonstrated that lymphatic invasion (HR: 1.457, 95% CI: 1.058–2.006, p = 0.021), T category (HR: 1.457, 95% CI: 1.058–2.006, p = 0.022), N category (HR: 1.535, 95% CI: 1.276–2.846, p < 0.001), stage (HR: 1.563, 95% CI: 1.235–1.976, p < 0.001) and the degree of venous invasion (HR: 1.526, 95% CI: 1.279–2.822, p < 0.001) were significant indicators of recurrence. The disease-free survival curves were distinguished especially well by the degree of venous invasion in stage III and IV patients.

Conclusions

The present study explored an objective grading criterion for VI and proved the prognostic value of the degree of venous invasion in ESCC. The classification of venous invasion into 4 groups is useful for the differentiation of prognosis in ESCC patients. The prognostic significance of the degree of VI in advanced ESCC patients for recurrence may have to be considered.
The impact of social capital and social environmental factors on mental health and flourishing: the experiences of asylum-seekers in France
Authors: De Jesus Maria , Warnock Bronwyn , Moumni Zoubida , Sougui Zara Hassan , Pourtau Lionel
Published: April 2023

Background

There is growing interest on how social capital and related social environmental factors impact overall population health and well-being. The nature of asylum-seekers’ social environment alters once they migrate to a new context and these changes influence their mental health and well-being. However, there is limited scholarship on how these social environmental factors impact the mental health, well-being, and capacity to flourish of asylum-seekers.

Methods

The aim of the study, therefore, was to examine how specific social environmental factors—social networks, social support, and social cohesion at various levels (micro, meso, and macro)—influence the mental health, well-being, and capacity to flourish of asylum-seekers in France. In collaboration with a community-based organization, we used a qualitative research design to conduct 120 semi-structured interviews with asylum-seekers in France.

Results

The emerging salient themes depicted how the asylum-seekers’ usual informal social networks comprised of family and friends had been disrupted since they migrated to France, which impacted their mental health and well-being. Conversely, staying connected with their informal transnational social networks via social media and developing ties with new local informal and formal social networks allowed them to receive different forms of social support, and buffered some of the negative mental health consequences. However, the lack of social cohesion due to a lack of belonging, marginalization, and current harmful migration-related policies impeded asylum-seekers’ capacity to flourish.

Conclusion

While social support derived from social networks buffered some negative impacts on mental health and well-being, the overall lack of social cohesion ultimately impeded asylum-seekers’ capacity to flourish within their host communities, which was further exacerbated by harmful migration policies of exclusion within France. Introducing more inclusive policies related to the governance of migration and an intersectoral approach that views health in all policies is key to promoting social cohesion and flourishing among asylum-seekers in France.