bluuebunny/crossref_metadata_2025 huggingface dataset:
Rural healthcare professionals’ participation in Medical Assistance in Dying (MAiD): beyond a binary decision
Authors: Sedgwick Monique , Brassolotto Julia , Manduca-Barone Alessandro
Published: April 2024

Background

Medical Assistance in Dying (MAiD) was legalized in Canada in 2016 and amended in 2021. At the time that this study was conducted, the federal government was considering expanding the eligibility criteria to include patients whose death was not reasonably foreseeable. The purpose of this study was to better understand rural healthcare professionals’ experiences with assisted dying set against the backdrop of legislative expansion.

Methods

A qualitative exploratory study was undertaken with general rural practice physicians, nurse practitioners, registered nurses, ethicists, patients, and patient families in rural Southern Alberta, Canada. For this paper, data from 18 audio-recorded and transcribed semi-structured interviews with healthcare professionals were analyzed using thematic analysis. Categories and patterns of shared meaning that linked to an overarching theme were identified.

Results

Between the binary positions of full support for and conscientious objection to assisted dying, rural healthcare professionals’ decisions to participate in MAiD was based on their moral convictions, various contextual factors, and their participation thresholds. Factors including patient suffering; personal and professional values and beliefs; relationships with colleagues, patients and family, and community; and changing MAiD policy and legislation created nuances that informed their decision-making.

Conclusions

The interplay of multiple factors and their degree of influence on healthcare professionals’ decision-making create multiple decision points between full support for and participation in MAiD processes and complete opposition and/or abstention. Moreover, our findings suggest evolving policy and legislation have the potential to increase rural healthcare professionals’ uncertainty and level of discomfort in providing services. We propose that the binary language typically used in the MAiD discourse be reframed to reflect that decision-making processes and actions are often fluid and situational.
Exploring medical and nursing students’ perceptions about a patient safety course: a qualitative study
Authors: Ayub Farwa , Afzal Noreen , Ali Wajid , Asif Fozia , ul Hassan Syed Sabih , Haque Ghazal , Ahmed Fasih Ali , Ajani Khairulnissa , Tharani Zahra , Jaffer Mehtab , Haider Adil H , Aboumatar Hanan J , Latif Asad
Published: April 2024

Background

Educating health professionals on patient safety can potentially reduce healthcare-associated harm. Patient safety courses have been incorporated into medical and nursing curricula in many high-income countries and their impact has been demonstrated in the literature through objective assessments. This study aimed to explore student perceptions about a patient safety course to assess its influence on aspiring health professionals at a personal level as well as to explore differences in areas of focus between medical and nursing students.

Methods

A dedicated patient safety course was introduced for year III medical and year II and IV nursing students at the Aga Khan University (2021–2022). As part of a post-course assessment, 577 participating students (184 medical and 393 nursing) wrote reflections on the course, detailing its influence on them. These free-text responses were thematically analyzed using NVivo.

Results

The findings revealed five major themes: acquired skills (clinical, interpersonal), understanding of medical errors (increased awareness, prevention and reduction, responding to errors), personal experiences with patient safety issues, impact of course (changed perceptions, professional integrity, need for similar sessions, importance of the topic) and course feedback (format, preparation for clinical years, suggestions). Students reported a lack of baseline awareness regarding the frequency and consequences of medical errors. After the course, medical students reported a perceptional shift in favor of systems thinking regarding error causality, and nursing students focused on human factors and error prevention. The interactive course format involving scenario-based learning was deemed beneficial in terms of increasing awareness, imparting relevant clinical and interpersonal skills, and changing perspectives on patient safety.

Conclusions

Student perspectives illustrate the benefits of an early introduction of dedicated courses in imparting patient safety education to aspiring health professionals. Students reported a lack of baseline awareness of essential patient safety concepts, highlighting gaps in the existing curricula. This study can help provide an impetus for incorporating patient safety as a core component in medical and nursing curricula nationally and across the region. Additionally, patient safety courses can be tailored to emphasize areas identified as gaps among each professional group, and interprofessional education can be employed for shared learning. The authors further recommend conducting longitudinal studies to assess the long-term impact of such courses.
The mediating role of flow in the relationship between simulation design and simulation educational satisfaction in korean nursing students: a cross-sectional study
Authors: Lee Eun-Kyung , Ji Eun-Joo
Published: April 2024

Background

In Korea, there has been recent interest in nursing simulation education. In nursing, simulation education has many advantages, such as improving nursing students’ problem-solving and judgment skills. Simulation education satisfaction is an indicator for evaluating educational performance from the learners’ perspective and an important criterion for the development and progress of nursing education. Therefore, based on NLN/Jeffries simulation theory, this study aims to identify the relationship between simulation design and educational satisfaction and to confirm the mediating effect of flow.

Methods

This cross-sectional study was conducted using 143 fourth-year nursing students who had participated in classes using simulations at three universities in Seoul, Daegu, and Jeonbuk. Data were collected from April 24 to May 3, 2023. Demographic data, simulation design scale (SDS), flow in simulation, and the educational satisfaction scale in simulation were collected via an online questionnaire. The collected data were analyzed through t-test, ANOVA, Scheffé test, and Pearson’s correlation coefficient using SPSS 25.0. The mediating effect of flow was analyzed through the three-stage mediation effect procedure using hierarchical regression analysis and the Sobel test.

Results

The simulation educational satisfaction had a statistically significant positive correlation with simulation design (r = .65, p < .001) and flow (r = .47, p < .001), and simulation design was positively correlated with the flow (r = .55, p < .001). The simulation design had a statistically significant effect on flow, which was the mediating variable (β = 0.55, p < .001). Additionally, simulation design had a statistically significant effect on simulation educational satisfaction (β = 0.56, p < .001). The significance of the mediating effect of flow on the relationship between simulation design and simulation educational satisfaction was investigated using the Sobel test, and the mediating effect of flow was found to be statistically significant (Z = 5.36, p < .001).

Conclusion

The significance of the current study lies in its confirmation of the link between simulation design and simulation educational satisfaction, as well as the mediating function of flow. Nursing students can achieve simulation educational satisfaction through simulation-based education if simulation educators follow best practices that improve flow through well-organized simulation design.
Differential expression and analysis of extrachromosomal circular DNAs as serum biomarkers in pulmonary arterial hypertension
Authors: Zhang Chun , Du Qiang , Zhou Xiao , Qu Tianyu , Liu Yingying , Ma Kai , Shen Ziling , Wang Qun , Zhang Zaikui , Zhang Ruifeng
Published: April 2024

Background

Extrachromosomal circular DNAs (eccDNAs) have been reported to play a key role in the occurrence and development of various diseases. However, the characterization and role of eccDNAs in pulmonary arterial hypertension (PAH) remain unclear.

Methods

In the discovery cohort, we first explored eccDNA expression profiles by Circle-sequencing analysis. The candidate eccDNAs were validated by routine polymerase chain reaction (PCR), TOPO-TA cloning and Sanger sequencing. In the validation cohort, 30 patients with PAH and 10 healthy controls were recruited for qPCR amplification to detect the candidate eccDNAs. Datas at the baseline were collected, including clinical background, biochemical variables, echocardiography and hemodynamic factors. Receiver operating characteristic curve was used to investigate the diagnostic effect of the eccDNA.

Results

We identified a total of 21,741 eccDNAs in plasma samples of 3 IPAH patients and 3 individuals in good health, and the expression frequency, GC content, length distribution, and genome distribution of the eccDNAs were thoroughly characterized and analyzed. In the validation cohort, 687 eccDNAs were differentially expressed in patients with IPAH compared with healthy controls (screening threshold: |FC|≥2 and P < 0.05). Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the specific eccDNAs in IPAH were significantly enriched in calcium channel activity, the mitogen-activated protein kinase pathway, and the wnt signaling pathway. Verification queue found that the expression of eccDNA-chr2:131208878–131,424,362 in PAH was considerably higher than that in healthy controls and exhibited a high level of accuracy in predicting PAH with a sensitivity of 86.67% and a specificity of 90%. Furthermore, correlation analysis disclosed a significant association between serum eccDNA-chr2:131208878–131,424,362 and mean pulmonary artery pressure (mPAP) (r = 0.396, P = 0.03), 6 min walking distance (6MWD) (r = -0.399, P = 0.029), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r = 0.685, P < 0.001) and cardiac index (CI) (r = − 0.419, P = 0.021).

Conclusions

This is the first study to identify and characterize eccDNAs in patients with PAH. We revealed that serum eccDNA-chr2:131208878–131,424,362 is significantly overexpressed and can be used in the diagnosis of PAH, indicating its potential as a novel non-invasive biomarker.
Neutrophil extracellular traps promote proliferation of pulmonary smooth muscle cells mediated by CCDC25 in pulmonary arterial hypertension
Authors: Sun Hongxiao , Du Zhanhui , Zhang Xu , Gao Shuai , Ji Zhixian , Luo Gang , Pan Silin
Published: April 2024

Background

Previous studies have indicated that neutrophil extracellular traps (NETs) play a pivotal role in pathogenesis of pulmonary arterial hypertension (PAH). However, the specific mechanism underlying the impact of NETs on pulmonary artery smooth muscle cells (PASMCs) has not been determined. The objective of this study was to elucidate underlying mechanisms through which NETs contribute to progression of PAH.

Methods

Bioinformatics analysis was employed in this study to screen for potential molecules and mechanisms associated with occurrence and development of PAH. These findings were subsequently validated in human samples, coiled-coil domain containing 25 (CCDC25) knockdown PASMCs, as well as monocrotaline-induced PAH rat model.

Results

NETs promoted proliferation of PASMCs, thereby facilitating pathogenesis of PAH. This phenomenon was mediated by the activation of transmembrane receptor CCDC25 on PASMCs, which subsequently activated ILK/β-parvin/RAC1 pathway. Consequently, cytoskeletal remodeling and phenotypic transformation occur in PASMCs. Furthermore, the level of NETs could serve as an indicator of PAH severity and as potential therapeutic target for alleviating PAH.

Conclusion

This study elucidated the involvement of NETs in pathogenesis of PAH through their influence on the function of PASMCs, thereby highlighting their potential as promising targets for the evaluation and treatment of PAH.
Did the prolonged residual efficacy of clothianidin products lead to a greater reduction in vector populations and subsequent malaria transmission compared to the shorter residual efficacy of pirimiphos-methyl?
Authors: Odjo Esdras Mahoutin , Akpodji Christian S. T. , Djènontin Armel , Salako Albert Sourou , Padonou Gil Germain , Adoha Constantin Jésukèdè , Yovogan Boulais , Adjottin Bruno , Tokponnon Filémon T. , Osse Razaki , Agbangla Clement , Akogbeto Martin C.
Published: April 2024

Background

The residual activity of a clothianidin + deltamethrin mixture and clothianidin alone in IRS covered more than the period of malaria transmission in northern Benin. The aim of this study was to show whether the prolonged residual efficacy of clothianidin-based products resulted in a greater reduction in vector populations and subsequent malaria transmission compared with the shorter residual efficacy of pirimiphos-methyl.

Methods

Human bait mosquito collections by local volunteers and pyrethrum spray collections were used in 6 communes under IRS monitoring and evaluation from 2019 to 2021. ELISA/CSP and species PCR tests were performed on Anopheles gambiae sensu lato (s.l.) to determine the infectivity rate and subspecies by commune and year. The decrease in biting rate, entomological inoculation rate, incidence, inhibition of blood feeding, resting density of An. gambiae s.l. were studied and compared between insecticides per commune.

Results

The An. gambiae complex was the major vector throughout the study area, acounting for 98.71% (19,660/19,917) of all Anopheles mosquitoes collected. Anopheles gambiae s.l. collected was lower inside treated houses (45.19%: 4,630/10,245) than outside (54.73%: 5,607/10,245) after IRS (p < 0.001). A significant decrease (p < 0.001) in the biting rate was observed after IRS in all departments except Donga in 2021 after IRS with clothianidin 50 WG. The impact of insecticides on EIR reduction was most noticeable with pirimiphos-methyl 300 CS, followed by the clothianidin + deltamethrin mixture and finally clothianidin 50 WG. A reduction in new cases of malaria was observed in 2020, the year of mass distribution of LLINs and IRS, as well as individual and collective protection measures linked to COVID-19. Anopheles gambiae s.l. blood-feeding rates and parous were high and similar for all insecticides in treated houses.

Conclusion

To achieve the goal of zero malaria, the optimal choice of vector control tools plays an important role. Compared with pirimiphos-methyl, clothianidin-based insecticides induced a lower reductions in entomological indicators of malaria transmission.
Effect of a vapor barrier in combination with active external rewarming for cold-stressed patients in a prehospital setting: a randomized, crossover field study
Authors: Mydske Sigurd , Brattebø Guttorm , Østerås Øyvind , Wiggen Øystein , Assmus Jörg , Thomassen Øyvind
Published: April 2024

Background

Use of a vapor barrier in the prehospital care of cold-stressed or hypothermic patients aims to reduce evaporative heat loss and accelerate rewarming. The application of a vapor barrier is recommended in various guidelines, along with both insulating and wind/waterproof layers and an active external rewarming device; however, evidence of its effect is limited. This study aimed to investigate the effect of using a vapor barrier as the inner layer in the recommended “burrito” model for wrapping hypothermic patients in the field.

Methods

In this, randomized, crossover field study, 16 healthy volunteers wearing wet clothing were subjected to a 30-minute cooling period in a snow chamber before being wrapped in a model including an active heating source either with (intervention) or without (control) a vapor barrier. The mean skin temperature, core temperature, and humidity in the model were measured, and the shivering intensity and thermal comfort were assessed using a subjective questionnaire. The mean skin temperature was the primary outcome, whereas humidity and thermal comfort were the secondary outcomes. Primary outcome data were analyzed using analysis of covariance (ANCOVA).

Results

We found a higher mean skin temperature in the intervention group than in the control group after approximately 25 min (p < 0.05), and this difference persisted for the rest of the 60-minute study period. The largest difference in mean skin temperature was 0.93 °C after 60 min. Humidity levels outside the vapor barrier were significantly higher in the control group than in the intervention group after 5 min. There were no significant differences in subjective comfort. However, there was a consistent trend toward increased comfort in the intervention group compared with the control group.

Conclusions

The use of a vapor barrier as the innermost layer in combination with an active external heat source leads to higher mean skin rewarming rates in patients wearing wet clothing who are at risk of accidental hypothermia.

Trial registration

ClinicalTrials.gov identifier: NCT05779722.
Statistical analysis plan for a cluster randomised trial in Madhya Pradesh, India: community health promotion and medical provision and impact on neonates (CHAMPION2)
Authors: Magill Nicholas , Shivalli Siddharudha , Fazzio Ila , Elbourne Diana , Keddie Suzanne , Reddy Padmanabh , Nair Rakhi , Gopal Madan , Karnati Sridevi , Reddy Harshavardhan , Boone Peter , Frost Chris
Published: April 2024

Background

Neonatal mortality in India has fallen steadily and was estimated to be 24 per 1000 live births in the year 2017. However, neonatal mortality remains high in rural parts of the country. The Community Health Promotion and Medical Provision and Impact On Neonates (CHAMPION2) trial investigates the effect of a complex health intervention on neonatal mortality in the Satna District of Madhya Pradesh.

Methods/design

The CHAMPION2 trial forms one part of a cluster-randomised controlled trial with villages (clusters) randomised to receive either a health (CHAMPION2) or education (STRIPES2) intervention. Villages receiving the health intervention are controls for the education intervention and vice versa. The primary outcome is neonatal mortality. The effect of the active intervention on the primary outcome (compared to usual care) will be expressed as a risk ratio, estimated using a generalised estimating equation approach with robust standard errors that take account of clustering at village level. Secondary outcomes include maternal mortality, stillbirths, perinatal deaths, causes of death, health care and knowledge, hospital admissions of enrolled women during pregnancy or in the immediate post-natal care period or of their babies (during the neonatal period), maternal blood transfusions, and the cost effectiveness of the intervention. A total of 196 villages have been randomised and over 34,000 women have been recruited in CHAMPION2.

Discussion

This update to the published trial protocol gives a detailed plan for the statistical analysis of the CHAMPION2 trial.

Trial registration

Registry of India: CTRI/2019/05/019296. Registered on 23 May 2019. https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MzExOTg=&Enc=&userName=champion2
The effect of movement system impairment-based classification treatment compared to routine physiotherapy on pain, disability, alignment, and movement impairments in individuals with tibiofemoral rotation syndrome: a randomized controlled trial
Authors: Mousavi Forouzan , Kajbafvala Mehrnaz , Mohsenifar Holakoo , Salehi Reza , Hejazi Anahita
Published: April 2024

Background

Knee pain is a common musculoskeletal problem. Lower extremity movement impairments could alter stresses in different planes and contribute to knee pain. Classifying these impairments may be helpful in the diagnosis and treatment of knee problems. Movement system impairment (MSI)-based classification is a system to evaluate movement impairments. Trials that involve this classification are limited. Therefore, it will be of interest to examine the effect of movement system impairment-based classification treatment compared to routine physiotherapy in individuals with tibiofemoral rotation syndrome.

Methods

Twenty-two individuals with knee pain aged 18–40 years (2 males, 20 females) diagnosed with tibiofemoral rotation (TFR) syndrome were included. After initial evaluation, individuals were randomly assigned into two treatment groups (MSI-based treatment and routine physiotherapy). Both treatment groups contained 8 treatment sessions over 4 weeks. Alignment and movement impairments data form, a numeric rating scale (NRS), and the Kujala Disability Questionnaire were assessed at baseline and after a four-week intervention. Independent samples t-test and Mann-Whitney U test were used for quantitative variables, and Fisher’s exact test was employed for qualitative variables to compare the groups. One-way Analysis of variance (ANOVA) and paired samples t-test were utilized to within-group changes of quantitative variables, and qualitative variables were analyzed with the McNemar test.

Results

The results showed that pain intensity and disability significantly decreased within and between groups after intervention (P > 0.05). There were also statistically significant differences between treatment groups for 3 out of 6 alignment and movement impairments (PS-FAdd/IR, Step down-Add/Valgus, and STS-Add/Valgus) (P > 0.05). Within-group differences for alignment and movement impairments were significant only for the MSI-based treatment group (P > 0.05).

Conclusions

The findings suggest that a specific MSI-based treatment, considering a homogenous group of individuals with knee pain, may contribute to pain, disability, and alignment and movement impairments improvement. Therefore, it is important to notice the classification-based treatment for individuals with knee pain.

Trial Registration Number (TRN) and date of registration

The trial was registered at the (https://www.irct.ir), (IRCT20210505051181N3) on 17/7/2021.
Associations of plasma neurofilament light chain with cognition and neuroimaging measures in community-dwelling early old age men
Authors: Tang Rongxiang , Buchholz Erik , Dale Anders M. , Rissman Robert A. , Fennema-Notestine Christine , Gillespie Nathan A. , Hagler Donald J , Lyons Michael J. , Neale Michael C. , Panizzon Matthew S. , Puckett Olivia K. , Reynolds Chandra A. , Franz Carol E. , Kremen William S. , Elman Jeremy A.
Published: April 2024

Background

Plasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations.

Methods

We examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61–73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter.

Results

After adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals.

Conclusions

These results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.
Ontological representation, modeling, and analysis of parasite vaccines
Authors: Huffman Anthony , Zhang Xumeng , Lanka Meghana , Zheng Jie , Masci Anna Maria , He Yongqun
Published: April 2024

Background

Pathogenic parasites are responsible for multiple diseases, such as malaria and Chagas disease, in humans and livestock. Traditionally, pathogenic parasites have been largely an evasive topic for vaccine design, with most successful vaccines only emerging recently. To aid vaccine design, the VIOLIN vaccine knowledgebase has collected vaccines from all sources to serve as a comprehensive vaccine knowledgebase. VIOLIN utilizes the Vaccine Ontology (VO) to standardize the modeling of vaccine data. VO did not model complex life cycles as seen in parasites. With the inclusion of successful parasite vaccines, an update in parasite vaccine modeling was needed.

Results

VIOLIN was expanded to include 258 parasite vaccines against 23 protozoan species, and 607 new parasite vaccine-related terms were added to VO since 2022. The updated VO design for parasite vaccines accounts for parasite life stages and for transmission-blocking vaccines. A total of 356 terms from the Ontology of Parasite Lifecycle (OPL) were imported to VO to help represent the effect of different parasite life stages. A new VO class term, ‘transmission-blocking vaccine,’ was added to represent vaccines able to block infectious transmission, and one new VO object property, ‘blocks transmission of pathogen via vaccine,’ was added to link vaccine and pathogen in which the vaccine blocks the transmission of the pathogen. Additionally, our Gene Set Enrichment Analysis (GSEA) of 140 parasite antigens used in the parasitic vaccines identified enriched features. For example, significant patterns, such as signal, plasma membrane, and entry into host, were found in the antigens of the vaccines against two parasite species: Plasmodium falciparum and Toxoplasma gondii. The analysis found 18 out of the 140 parasite antigens involved with the malaria disease process. Moreover, a majority (15 out of 54) of P. falciparum parasite antigens are localized in the cell membrane. T. gondii antigens, in contrast, have a majority (19/24) of their proteins related to signaling pathways. The antigen-enriched patterns align with the life cycle stage patterns identified in our ontological parasite vaccine modeling.

Conclusions

The updated VO modeling and GSEA analysis capture the influence of the complex parasite life cycles and their associated antigens on vaccine development.
Protocol for the development of a consensus practice guideline To address clinical and regulatory barriers to buprenorphine dispensing in community pharmacy
Authors: Varisco Tyler J. , Fish Hannah , Bolin Joshua , Dadiomov David , Hill Lucas G. , Essien Ekere J. , Wanat Matthew A. , Ginsburg Diane , Waggener Jeanne , Yazdanfard Sahar , Song Juhyeon , Chi Whanhui , Thornton Douglas
Published: April 2024

Background

Less than half of community pharmacies in the United States stock buprenorphine products indicated for the treatment of opioid use disorder. This lack of access to buprenorphine in community pharmacies is a significant barrier to care. To address this issue, this protocol outlines a comprehensive approach to develop a practice guideline aimed at improving access to safe and effective opioid use disorder treatment in community pharmacies.

Methods

The guideline development process will proceed in three phases, following a technique closely aligned with the Institute of Medicine’s guidance on guideline development. The first phase will involve conducting qualitative interviews with pharmacists in three states to identify their beliefs toward buprenorphine dispensing. As limitations on buprenorphine supply are related to constraints at all levels of the drug supply and regulatory system, the second phase, we will recruit representatives from regulatory agencies, pharmacy organizations, the Drug Enforcement Administration, pharmaceutical wholesalers as well as addiction medicine physicians and psychiatric pharmacists to develop consensus recommendations through a modified Delphi design. This will be followed by a public comment period and external expert review of the recommendations led by the National Association of Boards of Pharmacy. Finally, in the third phase, a national, mixed media dissemination campaign will be led by the National Community Pharmacists Association (NCPA) to convey recommendations to practicing pharmacists.

Discussion

The guideline development process aims to incorporate the perspectives of multiple stakeholders and emphasize the importance of addressing the regulatory and pharmacy-specific aspects of care in addition to clinical evidence and guidance. The development of this guideline will provide targeted, multidisciplinary guidance for pharmacists, improving access to safe and effective opioid use disorder treatment in the community setting.

Preregistration

This protocol was registered with the Open Science Framework in March of 2023. Registration may be found at: https://doi.org/10.17605/OSF.IO/6S9DY.
LINC complex alterations are a key feature of sporadic and familial ALS/FTD
Authors: Sirtori Riccardo , J. Gregoire Michelle , M. Potts Emily , Collins Alicia , Donatelli Liviana , Fallini Claudia
Published: April 2024

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects motor neurons, leading to progressive muscle weakness and loss of voluntary muscle control. While the exact cause of ALS is not fully understood, emerging research suggests that dysfunction of the nuclear envelope (NE) may contribute to disease pathogenesis and progression. The NE plays a role in ALS through several mechanisms, including nuclear pore defects, nucleocytoplasmic transport impairment, accumulation of mislocalized proteins, and nuclear morphology abnormalities. The LINC complex is the second biggest multi-protein complex in the NE and consists of the SUN1/2 proteins spanning the inner nuclear membrane and Nesprin proteins embedded in the outer membrane. The LINC complex, by interacting with both the nuclear lamina and the cytoskeleton, transmits mechanical forces to the nucleus regulating its morphology and functional homeostasis. In this study we show extensive alterations to the LINC complex in motor and cortical iPSC-derived neurons and spinal cord organoids carrying the ALS causative mutation in the C9ORF72 gene (C9). Importantly, we show that such alterations are present in vivo in a cohort of sporadic ALS and C9-ALS postmortem spinal cord and motor cortex specimens. We also found that LINC complex disruption strongly correlated with nuclear morphological alterations occurring in ALS neurons, independently of TDP43 mislocalization. Altogether, our data establish morphological and functional alterations to the LINC complex as important events in ALS pathogenic cascade, making this pathway a possible target for both biomarker and therapy development.
X-ray fluorescence analysis of three late medieval silver chalices associated with Ireland
Authors: Biolcati Veronica , McDonnell Richard Keyes , Hoffman Anna Grace , Ó Macháin Pádraig , Krasnodębska-D’Aughton Małgorzata , Iacopino Daniela
Published: April 2024

This paper presents the results of the first X-ray fluorescence (XRF) investigation conducted on three late medieval chalices associated with Ireland: the Ó Learghusa chalice, auctioned as medieval Irish in 2021, does not have a confirmed provenance; the de Burgo-O'Malley chalice, dated 1494, and the TP-IEP chalice, dated 1589, both of Irish provenance. This study effectively addressed the knowledge gap concerning Irish medieval silver chalices composition. The analysis revealed that both the Ó Learghusa and de Burgo-O'Malley chalices were crafted from a silver-copper alloy and adorned using a fire-gilding technique. The blue and green enamels on the de Burgo-O'Malley chalice were found to be constituted by cobalt and iron/copper glasses, respectively. In contrast, the TP-IEP chalice exhibited a more intricate structure, being a composite object with partial silver gilt and with the bowl and base possibly made of a ternary silver-copper-gold alloy. The TP-IEP chalice’s knop displayed glass, simulating gems with transparent, blue, and purple colorations. XRF analysis allowed identification of lead-potash glass, while the red glass displayed a rich iron content and was identified as soda-lime glass. The analysis allowed concluding that the de Burgo-O'Malley chalice had retained its original condition, including its original gilding and enamels, while the Ó Learghusa and TP-IEP chalices appeared to have undergone refurbishment. These significant discoveries contribute to a deeper understanding of the historical context and artistic craftsmanship behind these late medieval chalices, shedding light on their unique stories within Irish art and history.
11C-CFT PET brain imaging in Parkinson’s disease using a total-body PET/CT scanner
Authors: Sun Xiaolin , Tan Xiaoyue , Zhang Qing , He Shanzhen , Wang Siyun , Zhou Yongrong , Huang Qi , Jiang Lei
Published: April 2024

Purpose

This study aimed to evaluate the feasibility of 11C-CFT PET brain imaging in Parkinson’s Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice.

Methods

Thirty-two patients with Parkinson’s disease (PD) performing 11C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference.

Results

The overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P < 0.05). However, all G300 image quality was clinically acceptable (≥ 3 points). As the scan duration reduced, the SUVmean and DAT binding of caudate nucleus and putamen decreased progressively, while there were no statistically significant variations in the SUVmean of the background among the different groups. Moreover, the changes in the lesion DAT binding (ΔDAT-binding) between the full-time reference G900 image and other reconstructed group G720 to G30 images generally increased along with the reduced scan time.

Conclusion

Sufficient image quality and lesion conspicuity could be achieved at 600-s scan duration for 11C-CFT PET brain imaging in PD assessment using a total-body PET/CT scanner, while the image quality of G300 was acceptable to meet clinical diagnosis, contributing to improve patient compliance and throughput of PET brain imaging.
Integrating 5E Model with Planned-Incidental Grammar Teaching Approach to enhance grammar competency of eighth-grade Odia medium school students, in a time-sensitive manner
Authors: Behera Rashmi Ranjan , Rath Chirashree Srabani , Acharya Amulya Kumar , Subhrajyoti Trupti , Acharya Sujata , Kumar Rajesh
Published: April 2024

Prompted by the challenges faced by teachers in balancing grammar and content in English classes, coupled with the poor English proficiency of rural Odia medium school students, the study aimed to devise an intervention that could balance content and grammar, thereby enhancing the grammar competency and content comprehension of eighth-grade students. Based on quasi-experimental research with a pretest-posttest nonequivalent group design, two groups were assigned treatment conditions: the 5E Model with Planned-Incidental Grammar Teaching Approach (experimental group) and the traditional Grammar Translation Method (control group) during class instructions. Data were collected from 100 school students, with 52 in the experimental group and 48 in the control group, using pretest and posttest assessments. The mixed ANOVA test results revealed significantly higher posttest scores in the experimental group compared to the control group, highlighting the positive impact of the intervention on students’ grammar proficiency. The t-test for the comprehension test suggested comparable levels of comprehension in both groups, indicating the efficiency of the new pedagogical strategy in seamlessly integrating grammar instruction into regular classroom teaching, optimizing instructional time and ensuring balance between content and grammar, making it particularly valuable for educators facing time constraints. This study underscores the need for professional development opportunities to enhance teachers’ pedagogical skills and knowledge. Further research is warranted to explore the intervention’s impact on various language skills and assess its applicability in diverse contexts, contributing to a broader understanding of its implications.
School absence of adolescents from single-parent families in Andalusia (Spain): exploring the mediating and moderating role of economic and social resources
Authors: Mejías-Leiva Manuel , Moreno Mínguez Almudena
Published: April 2024

This study examines the relationship between growing up in single-parent families and school absence in Andalusia (Spain), considering differences according to adolescents’ social background. Empirical analyses of data from theSocial Survey 2010: Education and Housingshow that adolescents growing up in single-parent families have, on average, a higher number of school absences than their peers in two-parent families. These disadvantages are greater for adolescents with low social backgrounds, regardless of whether this is measured by parental education or housing tenure. Both economic resources (lower household income) and social resources (poor relationship with absent parent) partially explain the differences in school absence rates amongst adolescents growing up in single-parent families. School environment (teacher–student relationship, atmosphere amongst students, experiences of school violence or ownership of educational institution) are not influential in explaining educational disadvantage amongst adolescents from different family structures, although they are strong predictors of school absence.
Add-on multiple submucosal injections of the RNA oligonucleotide GUT-1 to anti-TNF antibody treatment in patients with moderate-to-severe ulcerative colitis: an open-label, proof-of concept study
Authors: Suzuki Kenji , Sameshima Yukinori , Yokoyama Junji , Terai Shuji , Yoneyama Hiroyuki , Atreya Raja , Neurath Markus F. , Hibi Toshifumi , Asakura Hitoshi
Published: April 2024

Background

Carbohydrate sulfotransferase 15 (CHST15) is an enzyme biosynthesizing matrix glycosaminoglycan that modulates tissue remodeling. We evaluated the efficacy of add-on submucosal injections of GUT-1, the RNA oligonucleotide inhibitor of CHST15, to ongoing anti-tumor necrosis factor (TNF) antibody treatment in patients with moderate-to-severe ulcerative colitis (UC).

Methods

This was an open-label study of 250 nM of GUT-1 by endoscopic submucosal injections at weeks 0, 2, 4 in five UC patients who lost response during maintenance treatment to anti-TNF antibodies. The primary endpoint was the rate of endoscopic improvement at week 6 and secondary endpoints included the rates of clinical remission by modified Mayo Score (mMS). Patients received follow-up observation with continuous maintenance treatment by the same anti-TNF antibody till the time of clinical recurrence or for overall 52 weeks.

Results

At week 6, rates of endoscopic improvement and clinical remission were 80% (n = 4/5) and 60% (n = 3/5), respectively. The mean Endoscopy Subscore was reduced from 2.4 (95%CI: 1.7 to 3.1) at baseline, to 1.0 (95%CI: 0.1 to 1.9) at week 6. The mean mMS was reduced from 7.8 (95%CI: 6.2 to 9.4) to 1.3 (95%CI: 2.9 to 4.3). GUT-1 was well tolerated. Three patients did not show clinical recurrence for 52 weeks. All three corticosteroid-dependent patients showed no corticosteroid exposure for at least 24 weeks after achieving clinical remission. Multiple dosing was also well tolerated.

Conclusions

Add-on multiple injections of GUT-1 to ongoing anti-TNF antibody was able to induce rapid and durable clinical responses in UC patients who lost response to anti-TNF therapy.

Trial registration

Clinical trial Registration Number (Japan): UMIN000020900.
Construction of new energy consumption optimization model based on improved pathfinder algorithm
Authors: Pan Zhen , Huang Feipeng , Lin Xin , Yu Ming
Published: April 2024

As traditional energy reserves continue to decline, the importance of new energy sources increases. However, the current traditional power system often fails to consider new energy sources, particularly in power supply systems that integrate multiple new energy sources. The cost, efficiency, and environmental factors seriously affect the energy system’s efficiency. Therefore, this proposal presents a multi-objective optimization discrete assignment pathfinder algorithm. The algorithm can handle multi-objective optimization problems and adapt to various constraints, providing a more precise optimization scheme for new energy systems. The experimental results indicated that the proposed research method exhibits better performance compared to other algorithms of the same type. Compared with the multi-objective multivariate universe optimization algorithm and the multi-objective sparrow search algorithm, the research method was ahead in terms of fitness value by 9.54% and 14.67%, respectively. Meanwhile, in the grid simulation, the research method achieved an average efficiency of 96.16%, which is better than the comparative algorithms by 6.57–14.02%. The study not only improves the optimization efficiency of new energy consumption, but also provides a powerful decision support tool for the planning and operation of wind farms. It is of great significance for the improvement of power system efficiency and decarbonization, and helps to promote the large-scale integration and sustainable development of new energy.
Temporal and spatial characterization of a thermogenic, fault-controlled gas hydrate system, Woolsey Mound, Gulf of Mexico
Authors: Alam Saiful , Knapp Camelia C. , Knapp James H. , Simonetti Antonello
Published: April 2024

Woolsey Mound, located at Mississippi Canyon Lease Block 118 (MC118), is the site of the Gulf of Mexico hydrate research consortium’s seafloor observatory, where gas hydrates outcrop at the seafloor. The presence of gas hydrates in the mound is confirmed directly by coring and indirectly by 3D seismic reflection data. Craters, pockmarks, chemosynthetic communities, and authigenic carbonates populate the seafloor at Woolsey Mound. Each crater is characterized by a network of shallow crestal faults that connect the hydrate mound to the underlying allochthonous salt body. We characterize the temporal and spatial evolution of gas hydrates at Woolsey Mound under natural perturbations using four collocated 3D seismic reflection data sets that span over 14 years. Data acquisition differences embedded in the data sets arising from variation in geometry, sample rate, and phase are minimized using the “cross-equalization” method. Our results indicate that hydrate formation and dissociation vary temporally and spatially in close connection to the shallow crestal faults. Evidence of gas hydrate dissociation is observed over a period of three years (2000–2003), where major dissociation occurred along the southern portion of the crestal fault in the southeast crater. The dissociation is less prominent in the southwest crater. Evidence of methane venting is observed between 2000 and 2010, which is mostly concentrated in the southeast crater. The residual amplitude anomalies observed between 2000 and 2014 in the mound are mostly positive, implying that the methane venting had increased significantly. The positive anomalies are correlated with the methane seepage recorded in 2011. Our results indicate the evolution of a fault-controlled gas hydrate system in the northern Gulf of Mexico, which would aid in assessing its impact on the seafloor.
Toward Equitable Precision Oncology: Monitoring Racial and Ethnic Inclusion in Genomics and Clinical Trials
Authors: García-Cárdenas Jennyfer M. , Indacochea Alberto , Pesantez-Coronel David , Terán-Navas Martín , Aleaga Ana , Armendáriz-Castillo Isaac , Peña Zúñiga Lizbeth , Morán-Erazo Carla , Chávez-Vélez Erik , Pérez-Villa Andy , López-Cortés Andrés , Guerrero Santiago
Published: April 2024

PURPOSE

Ethnic diversity in cancer research is crucial as race/ethnicity influences cancer incidence, survival, drug response, molecular pathways, and epigenetic phenomena. In 2018, we began a project to examine racial/ethnic diversity in cancer research, with a commitment to review these disparities every 4 years. This report is our second assessment, detailing the present state of racial/ethnic diversity in cancer genomics and clinical trials.

METHODS

To study racial/ethnic inclusion in cancer genomics, we extracted ethnic records from all data sets available at cBioPortal (n = 125,128 patients) and cancer-related genome-wide association studies (n = 28,011,282 patients) between 2018 and 2022. Concerning clinical trials, we selected studies related to breast cancer (n = 125,518 patients, 181 studies), lung cancer (n = 34,329 patients, 119 studies), and colorectal cancer (n = 40,808 patients, 105 studies).

RESULTS

In cancer genomics (N = 28,136,410), 3% of individuals lack racial/ethnic registries; tumor samples were collected predominantly from White patients (89.14%), followed by Asian (7%), African American (0.55%), and Hispanic (0.21%) patients and other populations (0.1%). In clinical trials (N = 200,655), data on race/ethnicity are missing for 60.14% of the participants; for individuals whose race/ethnicity was recorded, most were characterized as White (28.33%), followed by Asian (7.64%), African (1.79), other ethnicities (1.37), and Hispanic (0.73). Racial/ethnic representation significantly deviates from global ethnic proportions ( P ≤ .001) across all data sets, with White patients outnumbering other ethnic groups by a factor of approximately 4-6.

CONCLUSION

Our second update on racial/ethnic representation in cancer research highlights the persistent overrepresentation of White populations in cancer genomics and a notable absence of racial/ethnic information across clinical trials. To ensure more equitable and effective precision oncology, future efforts should address the reasons behind the insufficient representation of ethnically diverse populations in cancer research.