bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of 10 patients treated with the masquelet technique and microsurgical technique combined for Gustilo type III open tibial fractures
Authors: He Jingxuan , Xia Xiaofeng , Zuo Bing , Tang Jiaguo , Wang Peng
Published: May 2024

Background

Open tibial fractures often include severe bone loss and soft tissue defects and requires complex reconstructive operations. However, the optimal treatment is unclear.

Methods

This retrospective study enrolled patients with Gustilo type III open tibial fractures from January 2018 to January 2021 to assess the clinical utility of Masquelet technique together with microsurgical technique as a combined strategy for the treatment of open tibial fractures. The demographics and clinical outcomes including bone union time, infection, nonunion and other complications were recorded for analysis. The bone recovery quality was evaluated by the AOFAS Ankle-Hindfoot Scale score and the Paley criteria.

Results

We enrolled 10 patients, the mean age of the patients and length of bone defects were 31.7 years (range, 23–45 years) and 7.5 cm (range, 4.5–10 cm) respectively. Bone union was achieved for all patients, with an average healing time of 12.2 months (range, 11–16 months). Seven patients exhibited a bone healing time of less than 12 months, whereas 3 patients exhibited a bone healing time exceeding 12 months. No significant correlation was found between the length of bone loss and healing time. In addition, no deep infection or nonunion was observed, although 2 patients experienced wound fat liquefaction with exudates and 1 patient presented with a bloated skin flap. The average AOFAS Ankle-Hindfoot Scale score was 80.5 (range, 74–85), and all patients were evaluated as good or exellent based on the Paley criteria.

Conclusions

Our study indicated that the use of the Masquelet technique and the microsurgical technique as a combined strategy is safe and effective for the treatment of Gustilo type III open tibial fractures.
Effect of attachment flash on clear aligner force delivery: an in vitro study
Authors: Kiong Marisa , Ashari Asma , Zamani Nurul Syahira Mohamad , How Reuben Axel Wee Ming , Wahab Rohaya Megat Abdul , Mohamed Alizae Marny Fadzlin Syed , Lee HeeJeong Jasmine , Mokhtar Mohd Hadri Hafiz
Published: May 2024

Background

The introduction of auxiliaries such as composite attachment has improved the force delivery of clear aligner (CA) therapy. However, the placement of the attachment may give rise to a flash, defined as excess resin around the attachment which may affect CA force delivery. This in vitro study aims to determine the differences in the force generated by the attachment in the presence or absence of flash in CA.

Materials and methods

Tristar Trubalance aligner sheets were used to fabricate the CAs. Thirty-four resin models were 3D printed and 17 each, were bonded with ellipsoidal or rectangular attachments on maxillary right central incisors. Fuji Prescale pressure film was used to measure the force generated by the attachment of CA. The images of colour density produced on the films were processed using a calibrated pressure mapping system utilising image processing techniques and topographical force mapping to quantify the force. The force measurement process was repeated after the flash was removed from the attachment using tungsten-carbide bur on a slow-speed handpiece.

Results

The intraclass correlation coefficient showed excellent reliability (ICC = 0.96, 95% CI = 0.92–0.98). The average mean force exerted by ellipsoidal attachments with flash was 8.05 ± 0.16 N, while 8.11 ± 0.18 N was without flash. As for rectangular attachments, the average mean force with flash was 8.48 ± 0.27 N, while 8.53 ± 0.13 N was without flash. Paired t-test revealed no statistically significant difference in the mean force exerted by CA in the presence or absence of flash for both ellipsoidal (p = 0.07) and rectangular attachments (p = 0.41). Rectangular attachments generated statistically significantly (p < 0.001) higher mean force than ellipsoidal attachments for flash and without flash.

Conclusion

Although rectangular attachment generated a significantly higher force than ellipsoidal attachment, the force generated by both attachments in the presence or absence of flash is similar (p > 0.05).
Barriers and drivers of public engagement in palliative care, Scoping review
Authors: Barnestein-Fonseca Pilar , Nebro-Gil Alicia , Aguiar-Leiva Virginia P. , Víbora-Martín Eva , Ruiz-Torreras Inmaculada , Martín-Rosello Maria Luisa ,   on behalf iLIVE Group, van der Heide Agnes , Tripodoro Vilma , Veloso Verónica I. , Montilla Silvina , De Simone Gustavo G. , Goldraij Gabriel , Boughey Mark , Berger Michael , Fischer Claudia , Simon Judit , Voltz Raymond , Joshi Melanie , Strupp Julia , Halfdanardottir Svandis Iris , Sigurdardottir Valgerdur , Yildiz Berivan , Korfage Ida J. , Goossensen Anne , van Zuylen C. , Geijteman Eric C. T. , Allan Simon , Haugen Dagny Faksvåg , Iversen Grethe Skorpen , Lunder Urska , Bakan Misa , Kodba-Ceh Hana , Fürst Carl Johan , Schelin Maria E. C. , Eychmüller Steffen , Zambrano Sofia C. , Ellershaw John , Mason Stephen , McGlinchey Tamsin , Smeding Ruthmarijke
Published: May 2024

Background

The integral model of Palliative Care recognizes the community as essential element in improving quality of life of patients and families. It is necessary to find a formula that allows the community to have a voice. The aim of this scoping review is to identify barriers and facilitators to engage community in PC.

Methods

Systematic search was conducted in NICE, Cochrane Library, Health Evidence, CINAHL and PubMed database. Keywords: Palliative care, End of life care, community networks, community engagement, public engagement, community participation, social participation, barriers and facilitators.

Results

Nine hundred seventy-one results were obtained. Search strategy and inclusion criteria yielded 13 studies that were read in detail to identify factors influencing community engagement in palliative care, categorized into: Public health and public engagement; Community attitudes towards palliative care, death and preferences at the end of life; Importance of volunteers in public engagement programs; Compassionate communities.

Conclusion

Societal awareness must be a facilitated process to catalyse public engagement efforts. National policy initiatives and regional system support provide legitimacy and focus is essential for funding. The first step is to get a sense of what is important to society, bearing in mind cultural differences and to channel those aspects through health care professionals; connecting the most assistential part with community resources. The process and long-term results need to be systematically evaluated.
Quality of life and its related-influencing factors in patients with cervical cancer based on the scale QLICP-CE(V2.0)
Authors: Chen Huiyan , Zhou Lin , Fong Daniel , Cun Yingli , Yang Zheng , Wan Chonghua
Published: May 2024

Background

Quality of life research can guide clinical workers to adopt more targeted treatment and intervention measures, so as to achieve the purpose of improving patients’ quality of life. The objective of this study was to evaluate health-related quality of life in Chinese patients with cervical cancer and to explore its influencing factors.

Methods

A total of 186 patients with cervical cancer were investigated by using the QLICP-CE (V2.0) scale (Quality of Life Instruments for Cancer Patients-Cervical Cancer) developed by our group in China. The data were analyzed by t-test, one-way ANOVA, univariate analysis, and multivariate linear regression.

Results

The total score of quality of life scale for cervical cancer patients was (62.58 ± 12.69), Univariate analysis of objective clinical indexes showed that creatinine concentration was a negative influence factor in the psychological domain, potassium ion concentration was a negative influence factor in the common symptoms and side effect domain, erythrocyte content was a positive influence factor physical domain and common general domain. Multiple linear regression results suggested that clinical staging was the influencing factor of common symptom and side effect domain, common general module and total score of scale. Marital status has different degrees of influence on the psychological, social, and common general domains. The level of education also influenced scores in the social domain.

Conclusion

The total score of quality of life in patients with cervical cancer who received active treatment was acceptable. Marital status, clinical staging, and educational level are the factors that affect the quality of life of patients with cervical cancer. At the same time, potassium ion concentration, red blood cell count and creatinine concentration also have important effects on quality of life in patients with cervical cancer. Therefore, it is very important to give personalized treatment and nursing to patients based on various factors.
The impact of scheduling ketamine as an internationally controlled substance on anaesthesia care in Sub-Saharan Africa: a case study and key informant interviews
Authors: Ooms Gaby I. , Usman Mohammed A. , Reed Tim , van den Ham Hendrika A. , Mantel-Teeuwisse Aukje K.
Published: May 2024

Background

Access to anaesthesia and surgical care is a major problem for people living in Sub-Saharan Africa. In this region, ketamine is critical for the provision of anaesthesia care. However, efforts to control ketamine internationally as a controlled substance may significantly impact its accessibility. This research therefore aims to estimate the importance of ketamine for anaesthesia and surgical care in Sub-Saharan Africa and assess the potential impact on access to ketamine if it were to be scheduled.

Methods

This research is a mixed-methods study, comprising of a cross-sectional survey at the hospital level in Rwanda, and key informant interviews with experts on anaesthesia care in Sub-Saharan Africa. Data on availability of four anaesthetic agents were collected from hospitals (n = 54) in Rwanda. Semi-structured interviews with 10 key informants were conducted, collecting information on the importance of ketamine, the potential impact of scheduling ketamine internationally, and opinions on misuse of ketamine. Interviews were transcribed verbatim and analysed using a thematic analysis approach.

Results

The survey conducted in Rwanda found that availability of ketamine and propofol was comparable at around 80%, while thiopental and inhalational agents were available at only about half of the hospitals. Significant barriers impeding access to anaesthesia care were identified, including a general lack of attention given to the specialty by governments, a shortage of anaesthesiologists and migration of trained anaesthesiologists, and a scarcity of medicines and equipment. Ketamine was described as critical for the provision of anaesthesia care as a consequence of these barriers. Misuse of ketamine was not believed to be an issue by the informants.

Conclusion

Ketamine is critical for the provision of anaesthesia care in Sub-Saharan Africa, and its scheduling would have a significantly negative impact on its availability for anaesthesia care.
Exploring the experiences of adults with stroke in virtual community-based stroke programs: a qualitative descriptive study
Authors: Cruickshank Amy , Brooks Emma D’Andrea , Sperling Christina , Nelson Michelle LA , Singh Hardeep
Published: May 2024

Background

Stroke is among the top contributors to disability and can impact an individual’s cognition, physical functioning, and mental health. Since the COVID-19 pandemic, several community-based organizations have started delivering stroke programs virtually. However, participants’ experiences in these programs remain understudied, and evidence-based guidelines to inform and optimize virtual stroke program development and delivery are lacking. Thus, this study aimed to describe the perspectives and experiences of individuals with stroke who participated in virtual community-based organization stroke programs, including perceived access and participation facilitators and barriers and suggestions for improving these programs.

Methods

A qualitative descriptive design was used to gather participant experiences through semi-structured interviews. Audio-recorded interviews were conducted on Zoom and transcribed verbatim. Adult participants who had experienced a stroke and attended at least one Canadian virtual community-based organization stroke program were recruited. Data were analyzed using inductive thematic analysis.

Results

Twelve participants (32–69 years, 2–23 years post-stroke, eight women and four men) participated in this study. Five themes were identified: (1) motives to join virtual community-based organization stroke programs, including gaining peer connections, knowledge and information; (2) perceived barriers to accessing and participating in virtual community-based organization stroke programs, including technology inequities, difficulties navigating technology, and inadequate facilitation; (3) perceived facilitators to accessing and participating in virtual community-based organization stroke programs, including remote access, virtual platform features and program leader characteristics/skills; (4) unmet needs during virtual community-based organization stroke programs, including in-person connection and individualized support; and (5) suggestions and preferences for improving virtual community-based organization stroke programs, including program facilitation, content and format.

Conclusions

Study findings highlight opportunities to improve virtual community-based organization stroke programs to optimize participant experiences and outcomes. Addressing the barriers and suggestions identified in this study may improve virtual community-based organization stroke programs’ access and quality.
The role of healthcare providers and caregivers in monitoring critically ill children: a qualitative study in a tertiary hospital, southern Malawi
Authors: Mwale Daniel , Manda-Taylor Lucinda , Langton Josephine , Likumbo Alice , van Hensbroek Michael Boele ,   IMPALA Study team, Calis Job , Janssens Wendy , Pell Christopher
Published: May 2024

Background

Critically ill children require close monitoring to facilitate timely interventions throughout their hospitalisation. In low- and middle-income countries with a high disease burden, scarce paediatric critical care resources complicates effective monitoring. This study describes the monitoring practices for critically ill children in a paediatric high-dependency unit (HDU) in Malawi and examines factors affecting this vital process.

Methods

A formative qualitative study based on 21 in-depth interviews of healthcare providers (n = 12) and caregivers of critically ill children (n = 9) in the HDU along with structured observations of the monitoring process. Interviews were transcribed and translated for thematic content analysis.

Results

The monitoring of critically ill children admitted to the HDU was intermittent, using devices and through clinical observations. Healthcare providers prioritised the most critically ill children for more frequent monitoring. The ward layout, power outages, lack of human resources and limited familiarity with available monitoring devices, affected monitoring. Caregivers, who were present throughout admission, were involved informally in monitoring and flagging possible deterioration of their child to the healthcare staff.

Conclusion

Barriers to the monitoring of critically ill children in the HDU were related to ward layout and infrastructure, availability of accurate monitoring devices and limited human resources. Potential interventions include training healthcare providers to prioritise the most critically ill children, allocate and effectively employ available devices, and supporting caregivers to play a more formal role in escalation.
Temporal landscape and translational regulation of A-to-I RNA editing in mouse retina development
Authors: Yang Ludong , Yi Liang , Yang Jiaqi , Zhang Rui , Xie Zhi , Wang Hongwei
Published: May 2024

Background

The significance of A-to-I RNA editing in nervous system development is widely recognized; however, its influence on retina development remains to be thoroughly understood.

Results

In this study, we performed RNA sequencing and ribosome profiling experiments on developing mouse retinas to characterize the temporal landscape of A-to-I editing. Our findings revealed temporal changes in A-to-I editing, with distinct editing patterns observed across different developmental stages. Further analysis showed the interplay between A-to-I editing and alternative splicing, with A-to-I editing influencing splicing efficiency and the quantity of splicing events. A-to-I editing held the potential to enhance translation diversity, but this came at the expense of reduced translational efficiency. When coupled with splicing, it could produce a coordinated effect on gene translation.

Conclusions

Overall, this study presents a temporally resolved atlas of A-to-I editing, connecting its changes with the impact on alternative splicing and gene translation in retina development.
A proposed simplified definition of metabolic syndrome in children and adolescents: a global perspective
Authors: Zong Xin’nan , Kelishadi Roya , Kim Hae Soon , Schwandt Peter , Matsha Tandi E. , Mill Jose G. , Caserta Carmelo Antonio , Medeiros Carla Campos Muniz , Kollias Anastasios , Whincup Peter H. , Pacifico Lucia , López-Bermejo Abel , Zhao Min , Zheng Miaobing , Xi Bo
Published: May 2024

Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice.

We proposed a simplified definition for assessing MetS risk in youths aged 6–17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89–0.92) and 0.79 (0.78–0.81) when using the IDF or NCEP definition as the gold standard, respectively.

The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.
Exploring the extrachromosomal plasmid rDNA of Naegleria fowleri AY27 genotype II: A human brain-eating amoeba via high-throughput sequencing
Authors: Aurongzeb Muhammad , Talha Malik Hafiz Muhammad , Jahanzaib Muhammad , Hassan Syed Shah , Rashid Yasmeen , Aziz Tariq , Alharbi Metab
Published: May 2024

Naegleria fowleri, also known as brain-earing amoeba, causes severe and rapidly fatal CNS infection in humans called primary amebic meningoencephalitis (PAM). The DNA from the N. fowleri clinical isolate was sequenced for circular extrachromosomal ribosomal DNA (CERE - rDNA). The CERE contains 18 S, 5.8 S, and 28 S ribosomal subunits separated by internal transcribed spacers, 5 open reading frames (ORFs), and mostly repeat elements comprising 7268 bp out of 15,786 bp (46%). A wide variety of variations and recombination events were observed. Finally, the ORFs that comprised only 4 hypothetical proteins were modeled and screened against Zinc drug-like compounds. Two compounds [ZINC77564275 (ethyl 2-(((4-isopropyl-4 H-1,2,4-triazol-3-yl) methyl) (methyl)amino) oxazole-4-carboxylate) and ZINC15022129 (5-(2-methoxyphenoxy)-[2,2’-bipyrimidine]-4,6(1 H,5 H)-dione)] were finalized as potential druggable compounds based on ADME toxicity analysis. We propose that the compounds showing the least toxicity would be potential drug candidates after laboratory experimental validation is performed.
SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study
Authors: Lv Yanchen , Cheng Xin , Dong Qiang
Published: May 2024

Background

Sodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD.

Methods

Genetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations.

Results

A lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively.

Conclusions

SGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.
Growth differentiation factor 11 regulates high glucose-induced cardiomyocyte pyroptosis and diabetic cardiomyopathy by inhibiting inflammasome activation
Authors: Zhang Jing , Wang Guolong , Shi Yuxuan , Liu Xin , Liu Shuang , Chen Wendi , Ning Yunna , Cao Yongzhi , Zhao Yueran , Li Ming
Published: May 2024

Background

Diabetic cardiomyopathy (DCM) is a crucial complication of long-term chronic diabetes that can lead to myocardial hypertrophy, myocardial fibrosis, and heart failure. There is increasing evidence that DCM is associated with pyroptosis, a form of inflammation-related programmed cell death. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily, which regulates oxidative stress, inflammation, and cell survival to mitigate myocardial hypertrophy, myocardial infarction, and vascular injury. However, the role of GDF11 in regulating pyroptosis in DCM remains to be elucidated. This research aims to investigate the role of GDF11 in regulating pyroptosis in DCM and the related mechanism.

Methods and results

Mice were injected with streptozotocin (STZ) to induce a diabetes model. H9c2 cardiomyocytes were cultured in high glucose (50 mM) to establish an in vitro model of diabetes. C57BL/6J mice were preinjected with adeno-associated virus 9 (AAV9) intravenously via the tail vein to specifically overexpress myocardial GDF11. GDF11 attenuated pyroptosis in H9c2 cardiomyocytes after high-glucose treatment. In diabetic mice, GDF11 alleviated cardiomyocyte pyroptosis, reduced myocardial fibrosis, and improved cardiac function. Mechanistically, GDF11 inhibited pyroptosis by preventing inflammasome activation. GDF11 achieved this by specifically binding to apoptosis-associated speck-like protein containing a CARD (ASC) and preventing the assembly and activation of the inflammasome. Additionally, the expression of GDF11 during pyroptosis was regulated by peroxisome proliferator-activated receptor α (PPARα).

Conclusion

These findings demonstrate that GDF11 can treat diabetic cardiomyopathy by alleviating pyroptosis and reveal the role of the PPARα-GDF11-ASC pathway in DCM, providing ideas for new strategies for cardioprotection.
Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer
Authors: Kundu Moumita , Butti Ramesh , Panda Venketesh K. , Malhotra Diksha , Das Sumit , Mitra Tandrima , Kapse Prachi , Gosavi Suresh W. , Kundu Gopal C.
Published: May 2024

Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations.
Passive immunotherapy for Alzheimer’s disease: challenges & future directions
Authors: Yi Ling Xiao , Tan Eng King , Zhou Zhi Dong
Published: May 2024

Passive immunotherapy with specific antibodies targeting Amyloid β (Aβ) peptide or tubulin-associated unit (tau) protein has emerged as a promising therapeutic approach in Alzheimer’s disease (AD). However, in a recent phase III clinical study, Sperling et al. (N Engl J Med 10.1056/NEJMoa2305032, 2023) reported that solanezumab, a monoclonal antibody targeting Aβ peptide, failed to slow cognitive decline in AD patients. Previously, three other anti-Aβ antibodies, bapineuzumab, crenezumab, and gantenerumab, have also failed to show similar beneficial effects. In addition, three humanized antibodies targeting tau protein failed in their phase II trials. However, other anti-Aβ antibodies, such as lecanemab (a humanized mAb binds to soluble Aβ protofibrils), donanemab (a humanized mAb binds to insoluble, N-terminal truncated form of Aβ peptides) and aducanumab (a human mAb binds to the aggregated form of Aβ), have been shown to slow the decline of cognitive functions in early stage AD patients. The specific targets used in passive immunotherapy in these clinical trials may explain the divergent clinical outcomes. There are several challenges and limitations of passive immunotherapy using anti-Aβ antibodies and long term longitudinal studies are needed to assess their efficacy, side effects and cost effectiveness in a wider spectrum of subjects, from pre-dementia to more advanced dementia. A combination therapeutic approach using both anti-Aβ antibodies and other pharmaceutical agents should also be explored.
Evidence of SARS-CoV-2 convergent evolution in immunosuppressed patients treated with antiviral therapies
Authors: Feng Shuchen , Reid Gail E. , Clark Nina M. , Harrington Amanda , Uprichard Susan L. , Baker Susan C.
Published: May 2024

Background

The factors contributing to the accelerated convergent evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not fully understood. Unraveling the contribution of viral replication in immunocompromised patients is important for the early detection of novel mutations and developing approaches to limit COVID-19.

Methods

We deep sequenced SARS-CoV-2 RNA from 192 patients (64% hospitalized, 39% immunosuppressed) and compared the viral genetic diversity within the patient groups of different immunity and hospitalization status. Serial sampling of 14 patients was evaluated for viral evolution in response to antiviral treatments.

Results

We identified hospitalized and immunosuppressed patients with significantly higher levels of viral genetic diversity and variability. Further evaluation of serial samples revealed accumulated mutations associated with escape from neutralizing antibodies in a subset of the immunosuppressed patients treated with antiviral therapies. Interestingly, the accumulated viral mutations that arose in this early Omicron wave, which were not common in the patient viral lineages, represent convergent mutations that are prevalent in the later Omicron sublineages, including the XBB, BA.2.86.1 and its descendent JN sublineages.

Conclusions

Our results illustrate the importance of identifying convergent mutations generated during antiviral therapy in immunosuppressed patients, as they may contribute to the future evolutionary landscape of SARS-CoV-2. Our study also provides evidence of a correlation between SARS-CoV-2 convergent mutations and specific antiviral treatments. Evaluating high-confidence genomes from distinct waves in the pandemic with detailed patient metadata allows for discerning of convergent mutations that contribute to the ongoing evolution of SARS-CoV-2.
Efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy for malignant pleural effusion: a meta-analysis
Authors: Pan Xue , Hou Zhichao , Zhang Tangjuan , Ding Zheng , Ye Fei , Wang Zhulin , Huang Chunyao , Wang Peng , Li Xiangnan
Published: May 2024

Objective

To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE).

Methods

PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0.

Results

Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P < 0.05] and life quality improvement rate [RR = 2.88, 95%CI (1.95, 4.24), P < 0.05] than those in the IPC group. IPHC and IPC for MPE patients had similar incidence rates of asthenia, thrombocytopenia, hepatic impairment, and leukopenia.

Conclusion

Compared with IPC, IPHC has a higher objective response rate without significantly increasing adverse reactions. Therefore, IPHC is effective and safe. However, this study is limited by the quality of the literature. Therefore, more high-quality, multi-center, large-sample, rigorously designed randomized controlled clinical studies are still needed for verification and evaluation.
Anomalous circumflex artery encircling the aortic annulus: implications for mitral valve repair
Authors: Portoghese Michele , Mureddu Simone , Balata Andrea , Contini Cristina , Carta Giangiacomo
Published: May 2024

Injury to coronary arteries during mitral surgery is a rare but life-threatening procedural complication, an anomalous origin and course of the left circumflex artery (LCx) increase this risk. Recognizing the anomaly by the characteristic angiographic pattern and identifying its relationship with the surrounding anatomical structure using imaging techniques, mainly transesophageal echocardiography (TOE) or coronary computed tomography angiography (CCTA), is of crucial importance in setting up the best surgical strategy. We report a case of anomalous origin of a circumflex artery (LCx) from the proximal portion of the right coronary artery (RCA) with a pathway running retroaortically through the mitro-aortic space. An integrated diagnostic approach using a multidisciplinary team with a cardiologist and an imaging radiologist allowed us to decide the surgical strategy. We successfully performed a mitral valvular repair using a minimally invasive minithoracotomic approach and implanting a complete semirigid ring.
Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program
Authors: Giugliani Roberto , Gonzalez-Meneses Antonio , Scarpa Maurizio , Burton Barbara , Wang Raymond , Martins Esmeralda , Oussoren Esmeralda , Hennermann Julia B. , Chabrol Brigitte , Grant Christina L. , Sun Angela , Durand Consuelo , Hetzer Joel , Malkus Betsy , Marsden Deborah , Merritt II J. Lawrence
Published: May 2024

Background

Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.

Methods

This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022.

Results

As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and − 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died.

Conclusions

To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.
Investigating the effects of synbiotic supplementation on functional movement, strength and muscle health in older Australians: a study protocol for a double-blind, randomized, placebo-controlled trial
Authors: Barry David J. , Farragher Joshua B. , Betik Andrew C. , Fyfe Jackson J. , Convit Lilia , Cooke Matthew B.
Published: May 2024

Background

Aging has been associated with a progressive loss of skeletal muscle quality, quantity and strength, which may result in a condition known as sarcopenia, leading to a decline in physical performance, loss of independence and reduced quality of life. While the cause of impaired physical functioning observed in elderly populations appears to be multifactorial, recent evidence suggests that age-associated alterations in gut microbiota could be a contributing factor. The primary objective will be to assess the effects of a dietary synbiotic formulation on sarcopenia-related functional outcomes such as handgrip strength, gait speed and physical performance within older individuals living independently. The secondary objective will be to examine associations between changes in gut microbiota composition, functional performance and lean muscle mass.

Methods

Seventy-four elderly (60–85 years) participants will be randomized in a double-blind, placebo-controlled fashion to either an intervention or control group. The intervention group (n = 37) will receive oral synbiotic formulation daily for 16 weeks. The control group (n = 37) will receive placebo. Assessments of physical performance (including Short Physical Performance Battery, handgrip strength and timed up-and-go tests) and muscle ultrasonography will be performed at 4 time points (baseline and weeks 8, 16 and 20). Likewise, body composition via bioelectric impedance analysis and blood and stool samples will be collected at each time point. Dual-energy X-ray absorptiometry will be performed at baseline and week 16. The primary outcomes will be between-group changes in physical performance from baseline to 16 weeks. Secondary outcomes include changes in body composition, muscle mass and architecture, fecal microbiota composition and diversity, and fecal and plasma metabolomics.

Discussion

Gut-modulating supplements appear to be effective in modifying gut microbiota composition in healthy older adults. However, it is unclear whether these changes translate into functional and/or health improvements. In the present study, we will investigate the effects of a synbiotic formulation on measures of physical performance, strength and muscle health in healthy older populations.

Trial registration

This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000652774) in May 2022.
Rapid fractionation of corn stover by microwave-assisted protic ionic liquid [TEA][HSO4] for fermentative acetone–butanol–ethanol production
Authors: Wang Yankun , Cai Di , Jiang Yongjie , Mei Xueying , Ren Wenqiang , Sun Mingyuan , Su Changsheng , Cao Hui , Zhang Changwei , Qin Peiyong
Published: May 2024

Background

The use of ionic liquids (ILs) to fractionate lignocelluloses for various bio-based chemicals productions is in the ascendant. On this basis, the protic ILs consisting of triethylammonium hydrogen sulfate ([TEA][HSO4]) possessed great promise due to the low price, low pollution, and high efficiency. In this study, the microwave-assistant [TEA][HSO4] fractionation process was established for corn stover fractionation, so as to facilitate the monomeric sugars production and supported the downstream acetone–butanol–ethanol (ABE) fermentation.

Results

The assistance of microwave irradiation could obviously shorten the fractionation period of corn stover. Under the optimized condition (190 W for 3 min), high xylan removal (93.17 ± 0.63%) and delignification rate (72.90 ± 0.81%) were realized. The mechanisms for the promotion effect of the microwave to the protic ILs fractionation process were ascribed to the synergistic effect of the IL and microwaves to the depolymerization of lignocellulose through the ionic conduction, which can be clarified by the characterization of the pulps and the isolated lignin specimens. Downstream valorization of the fractionated pulps into ABE productions was also investigated. The [TEA][HSO4] free corn stover hydrolysate was capable of producing 12.58 g L−1 of ABE from overall 38.20 g L−1 of monomeric sugars without detoxification and additional nutrients supplementation.

Conclusions

The assistance of microwave irradiation could significantly promote the corn stover fractionation by [TEA][HSO4]. Mass balance indicated that 8.1 g of ABE and 16.61 g of technical lignin can be generated from 100 g of raw corn stover based on the novel fractionation strategy.
Evaluating the mosquito vector range for two orthobunyaviruses: Oya virus and Ebinur Lake virus
Authors: Liu Siyuan , Wang Xiaoyu , Wang Fei , Zaman Wahid , Yang Cihan , Huang Doudou , Ma Haixia , Wang Jinglin , Liu Qiyong , Yuan Zhiming , Xia Han
Published: May 2024

Background

Mosquito-borne viruses cause various infectious diseases in humans and animals. Oya virus (OYAV) and Ebinur Lake virus (EBIV), belonging to the genus Orthobunyavirus within the family Peribunyaviridae, are recognized as neglected viruses with the potential to pose threats to animal or public health. The evaluation of vector competence is essential for predicting the arbovirus transmission risk.

Methods

To investigate the range of mosquito vectors for OYAV (strain SZC50) and EBIV (strain Cu20-XJ), the susceptibility of four mosquito species (Culex pipiens pallens, Cx. quinquefasciatus, Aedes albopictus, and Ae. aegypti) was measured through artificial oral infection. Then, mosquito species with a high infection rate (IR) were chosen to further evaluate the dissemination rate (DR), transmission rate (TR), and transmission efficiency. The viral RNA in each mosquito sample was determined by RT-qPCR.

Results

The results revealed that for OYAV, Cx. pipiens pallens had the highest IR (up to 40.0%) among the four species, but the DR and TR were 4.8% and 0.0%, respectively. For EBIV, Cx. pipiens pallens and Cx. quinquefasciatus had higher IR compared to Ae. albopictus (1.7%). However, the EBIV RNA and infectious virus were detected in Cx. pipiens pallens, with a TR of up to 15.4% and a transmission efficiency of 3.3%.

Conclusions

The findings indicate that Cx. pipiens pallens was susceptible to OYAV but had an extremely low risk of transmitting the virus. Culex pipiens pallens and Cx. quinquefasciatus were susceptible to EBIV, and Cx. pipiens pallens had a higher transmission risk to EBIV than Cx. quinquefasciatus.

Graphical Abstract
The effects of kettlebell training versus resistance training using the own body mass on physical fitness and physiological adaptations in obese adults: a randomized controlled trial
Authors: Govindasamy Karuppasamy , Gogoi Hemantajit , Jebabli Nidhal , Bediri Sultan Mansour , Aljahni Mohammed , Parpa Koulla , Clark Cain C. T. , Granacher Urs , Zouhal Hassane
Published: May 2024

Aim of study

This study aimed to explore the effects of different types of resistance training using kettlebells versus the own body mass, in comparison to a passive control, on key physical fitness and physiological parameters in young, obese adults.

Methods

Data from 60 sedentary, obese male college students, aged 17–26, were used for final analyses. Participants were randomly assigned to one of three groups: a control group (CG,n = 20, no training), a kettlebell resistance training group (KRTG,n = 20), or a bodyweight resistance training group (BWRTG,n = 20). Selected measures of physical fitness were tested using the 12-minutes run test, the push-up test, the sit-up test, and the sit-and-reach test. Physiological measures included vital capacity, resting and maximum heart rate (HRmax), mean arterial blood pressure, breath holding time, and respiratory rate. Biochemical variables were measured in the morning, in a fasted state, and comprised high and low density lipoprotein, total cholesterol, and triglycerides. The 12-weeks progressive KRTG and BWRTG were specifically tailored using sets, repetitions, and intensity levels.

Results

Notable findings include significant body fat reductions in BWRTG (p < 0.001; d = 1.53) and KRTG (p < 0.001; d = 1.43), and a substantial increase in VO2max for BWRTG (p < 0.001; d = 1.32) and KRTG (p < 0.001; d = 1.34) compared to CG. KRTG also showed significant improvements in vital capacity (p < 0.001; d = 1.61) and reductions in resting heart rate (p = 0.024, d = 1.05) and respiratory rate (p = 0.001, d = 1.55), with BWRTG showing similar trends (resting heart rate:p = 0.041, d = 1.35; respiratory rate:p = 0.001, d = 1.98). Both intervention groups significantly improved breath holding time (KRTG:p = 0.001, d = 1.58; BWRTG:p < 0.001, d = 1.98) and reduced total cholesterol and low-density lipoprotein levels compared to CG.

Conclusions

This study demonstrates that both KRTG and BWRTG are effective in improving body composition and selected fitness and physiological measures. Thus, resistance training using kettlebells or bodyweight training are recommended if the goal is to improve body composition and fitness in obese male adults.

Trial Registration

OSF, September, 28th 2023.https://doi.org/10.17605/OSF.IO/Z6Y9Gosf.io/2mb98
Osteoinductive micro-nano guided bone regeneration membrane for in situ bone defect repair
Authors: Wang Bingqian , Xie Xinfang , Jiang Wenbin , Zhan Yichen , Zhang Yifan , Guo Yaqi , Wang Zhenxing , Guo Nengqiang , Guo Ke , Sun Jiaming
Published: May 2024

Background

Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects.

Methods

The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane’s potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining.

Results

The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone.

Conclusions

The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.