bluuebunny/crossref_metadata_2025 huggingface dataset:
Degradation effects of dietary solvents on microhardness and inorganic elements of computer-aided design/computer-aided manufacturing dental composites
Authors: Munusamy Selva Malar , Helen-Ng Lee Ching , Farook Mohideen Salihu
Published: February 2024

Background

Computer-aided design/computer-aided manufacturing (CAD/CAM) dental composites were introduced with superior mechanical properties than conventional dental composites. However, little is known on effects of dietary solvents on microhardness or inorganic elemental composition of CAD/CAM composites.

Objectives

The objectives of this study were to evaluate the degradation effects of each dietary solvent on the microhardness of the different CAD/CAM dental composites and to observe the degradation effects of dietary solvent on the inorganic elements of the dental composites investigated.

Methods

Fifty specimens with dimensions 12 mm x 14 mm x 1.5 mm were prepared for direct composite (Filtek Z350 XT [FZ]), indirect composite (Shofu Ceramage [CM]), and three CAD/CAM composites (Lava Ultimate [LU], Cerasmart [CS], and Vita Enamic [VE]). The specimens were randomly divided into 5 groups (n = 10) and conditioned for 1-week at 37°C in the following: air (control), distilled water, 0.02 N citric acid, 0.02 N lactic acid and 50% ethanol-water solution. Subsequently, the specimens were subjected to microhardness test (KHN) using Knoop hardness indenter. Air (control) and representative postconditioning specimens with the lowest mean KHN value for each material were analyzed using energy dispersive X-ray spectroscopy (EDX). Statistical analysis was done using one-way ANOVA and post hoc Bonferroni test at a significance level of p = 0.05.

Results

Mean KHN values ranged from 39.7 ± 2.7 kg/mm2 for FZ conditioned in 50% ethanol-water solution to 79.2 ± 3.4 kg/mm2 for VE conditioned in air (control). With exception to LU, significant differences were observed between materials and dietary solvents for other dental composites investigated. EDX showed stable peaks of the inorganic elements between air (control) and representative postconditioning specimens.

Conclusions

The microhardness of dental composites was significantly affected by dietary solvents, except for one CAD/CAM composite [LU]. However, no changes were observed in the inorganic elemental composition of dental composites between air (control) and 1-week postconditioning.
A systematic review of the childbearing needs of single-child couples
Authors: Seraj Shirvan Fatemeh , Moradi Maryam , Latifnejad Ruodsari Robab
Published: February 2024

Background

Nowadays, the challenge of having single child is spreading in many countries. Only- child family is prevalent in 26% of families in Canada, 21% in the United States, 47.5% in Europe and 20% in Iran, which can lead to fertility below replacement level. Therefore, the current review was conducted to identify the needs of single-child couples.

Methods

The PRISMA checklist was used to prepare this systematic review report. English and Persian articles published between 2000 and April 2023 were searched in the English databases of ISI, PubMed, Cochrane library and Google Scholar search engine as well as Persian databases of SID and Magiran using keywords of only child, needs assessment and Reproductive behavior. All cross-sectional and correlational studies that addressed the needs of single-child couples were included in the study. The quality assessment of the articles was done by the STROBE checklist. Data extraction was done by two independent researchers using a self-structured checklist. To analyze the data, following tabulating the extracted data, the process of qualitative synthesis was done for systematic review taking into account ethical considerations.

Results

Out of 1,581 articles found, 17 articles were included in the systematic review. The needs of single-child couples were divided into four general areas included 1) Financial needs, 2) Cultural needs, 3) Educational needs, and 4) Supportive needs. The support needs included two kinds of social and family support.

Conclusion

Solving financial needs, creating a culture of positive values of childbearing and men's participation in household affairs, considering women's preferences in order to increase education and employment, childbearing training and counseling and creating social and family support in line with work and family harmony and quality care of children, as the most important needs of single-child couples, should be incorporated in the formulation of childbearing incentive programs.
Mapping an undergraduate medical education curriculum against national and international palliative care reference learning objectives
Authors: Murphy Rebekah , Barnes Christopher J. , Enright Paula D. , Gratton Valerie , Bush Shirley H.
Published: February 2024

Background

The teaching of palliative care competencies is an essential component of undergraduate medical education. There is significant variance in the palliative care content delivered in undergraduate medical curricula, revealing the utility of reference standards to guide curricular development and assessment. To evaluate our university’s undergraduate palliative care teaching, we undertook a curriculum mapping exercise, comparing official learning objectives to the national Educating Future Physicians in Palliative and End-of-Life Care (EFPPEC) and the international Palliative Education Assessment Tool (PEAT) reference objectives.

Methods

Multiple assessors independently compared our university’s UGME learning objectives with EFPPEC and PEAT reference objectives to determine the degree-of-coverage. Visual curriculum maps were created to depict in which part of the curriculum each objective is delivered and by which medical specialty.

Results

Of 122 EFPPEC objectives, 55 (45.1%) were covered fully, 42 (34.4%) were covered partially, and 25 (20.5%) were not covered by university objectives. Of 89 PEAT objectives, 40 (44.9%) were covered fully, 35 (39.3%) were covered partially, and 14 (15.7%) were not covered by university objectives.

Conclusions

The majority of EFPPEC and PEAT reference objectives are fully or partially covered in our university’s undergraduate medical curriculum. Our approach could serve as a guide for others who endeavour to review their universities’ specialty-specific medical education against reference objectives. Future curriculum development should target the elimination of identified gaps and evaluate the attainment of palliative care competencies by medical learners.
End-of-life and bereavement support to families in cancer care: a cross-sectional survey with bereaved family members
Authors: Thaqi Qëndresa , Riguzzi Marco , Blum David , Peng-Keller Simon , Lorch Anja , Naef Rahel
Published: February 2024

Background

Losing a close other to cancer is an incisive experience that occurs after a long course of illness and intense family caregiving. Despite an evident need for family engagement and support and guidance on this, patients and family members may not receive the attention and support they need when a family unit is experiencing a disruption by death. A clear understanding of the quality of care that is currently provided and its ability to address family needs is necessary to improve end-of-life and bereavement support to families affected by cancer. The purpose of this study is to investigate the quality of support of end-of-life and bereavement care to families, their (un)met needs, grief experiences, and self-perceived health outcomes.

Methods

A multi-center, cross-sectional observational survey study with family members (n = 35) whose close other died of cancer in a health institution or their own home in German-speaking Switzerland.

Results

Bereaved family members were mostly satisfied with end-of-life care. Information on the grief process and services, and acknowledgment of their grief was experienced as helpful. Most coped with their grief drawing on family resources and exhibited resilience, but they reported unmet needs in relation to family togetherness and caregiving.

Conclusion

This study with a small number of family members indicates that support provided to families across settings and illness trajectories is perceived as helpful, with specific needs related to family support. The findings suggest that improvements should focus on ensuring care that addresses the family as a unit and enables togetherness, mutual reflection, meaningful relationships, preparedness for death, resilience, and benefit-finding.

Protocol registration

https://osf.io/j4kfh.
Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes
Authors: Gamez Monica , Elhegni Hesham E. , Fawaz Sarah , Ho Kwan Ho , Campbell Neill W. , Copland David A. , Onions Karen L. , Butler Matthew J. , Wasson Elizabeth J. , Crompton Michael , Ramnath Raina D. , Qiu Yan , Yamaguchi Yu , Arkill Kenton P. , Bates David O. , Turnbull Jeremy E. , Zubkova Olga V. , Welsh Gavin I. , Atan Denize , Satchell Simon C. , Foster Rebecca R.
Published: February 2024

Background

Diabetes mellitus is a chronic disease which is detrimental to cardiovascular health, often leading to secondary microvascular complications, with huge global health implications. Therapeutic interventions that can be applied to multiple vascular beds are urgently needed. Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are characterised by early microvascular permeability changes which, if left untreated, lead to visual impairment and renal failure, respectively. The heparan sulphate cleaving enzyme, heparanase, has previously been shown to contribute to diabetic microvascular complications, but the common underlying mechanism which results in microvascular dysfunction in conditions such as DR and DKD has not been determined.

Methods

In this study, two mouse models of heparan sulphate depletion (enzymatic removal and genetic ablation by endothelial specific Exotosin-1 knock down) were utilized to investigate the impact of endothelial cell surface (i.e., endothelial glycocalyx) heparan sulphate loss on microvascular barrier function. Endothelial glycocalyx changes were measured using fluorescence microscopy or transmission electron microscopy. To measure the impact on barrier function, we used sodium fluorescein angiography in the eye and a glomerular albumin permeability assay in the kidney. A type 2 diabetic (T2D, db/db) mouse model was used to determine the therapeutic potential of preventing heparan sulphate damage using treatment with a novel heparanase inhibitor, OVZ/HS-1638. Endothelial glycocalyx changes were measured as above, and microvascular barrier function assessed by albumin extravasation in the eye and a glomerular permeability assay in the kidney.

Results

In both models of heparan sulphate depletion, endothelial glycocalyx depth was reduced and retinal solute flux and glomerular albumin permeability was increased. T2D mice treated with OVZ/HS-1638 had improved endothelial glycocalyx measurements compared to vehicle treated T2D mice and were simultaneously protected from microvascular permeability changes associated with DR and DKD.

Conclusion

We demonstrate that endothelial glycocalyx heparan sulphate plays a common mechanistic role in microvascular barrier function in the eye and kidney. Protecting the endothelial glycocalyx damage in diabetes, using the novel heparanase inhibitor OVZ/HS-1638, effectively prevents microvascular permeability changes associated with DR and DKD, demonstrating a novel systemic approach to address diabetic microvascular complications.
Prevalence of helmintic infections in Brazilian Maxakali indigenous: a repeated cross-sectional design
Authors: Nacife Maria Beatriz Pena e Silva Leite , Siqueira Liliane Maria Vidal , Barbosa Keila Furbino , Vianna Valeska Natiely , Masioli Cássio Zumerle , da Silva Jaime Costa , Zicker Fábio , Coelho Paulo Marcos Zech , Katz Naftale , Machado-Coelho George Luiz Lins
Published: February 2024

Background

The prevalence of intestinal parasites is known to be high among Amerindian populations; further, there are serious problems in the healthcare of these populations in Brazil. The Maxakali, located in the northeastern region of Minas Gerais, Brazil, is an indigenous group that still preserves many of its cultural aspects. This study aimed to compare the positivity rate of schistosomiasis and soil-transmitted helminths in this ethnic group in epidemiological surveys conducted in 1972 and 2014.

Methods

Stool parasitological examinations were performed by the Kato-Katz technique during both periods in this population. In 2014, the parasitological diagnosis was also realized with the TF-Test® technique.

Results

In 1972, 270 inhabitants were examined. The positivity rates were 67.4% for Schistosoma mansoni, 72.9% for hookworms, 43.7% for Ascaris lumbricoides, and 23.7% for Trichuris trichiura. In 2014, 545 individuals were examined, and the positivity rates obtained were 45.7% for S. mansoni, 22.8% for hookworms, 0.6% for A. lumbricoides, and 2.8% for T. trichiura.

Conclusions

The comparison of the parasitological surveys conducted in 1972 and 2014, indicates that the indigenous Maxakali remained neglected by the health and indigenous protection authorities during these four decades. The infection rate observed in 2014 for schistosomiasis and hookworm remains high, considering the current epidemiological view of these diseases in the Brazilian population.
Impact of driving cessation on health-related quality of life trajectories
Authors: Mielenz Thelma J. , Jia Haomiao , DiGuiseppi Carolyn , Molnar Lisa J. , Strogatz David , Hill Linda L. , Andrews Howard F. , Eby David W. , Jones Vanya C. , Li Guohua
Published: February 2024

Background

Trajectories of health-related quality of life (HRQoL) after driving cessation (DC) are thought to decline steeply, but for some, HRQoL may improve after DC. Our objective is to examine trajectories of HRQoL for individuals before and after DC. We hypothesize that for urban drivers, volunteers and those who access alternative transportation participants’ health may remain unchanged or improve.

Methods

This study uses data from the AAA Longitudinal Research on Aging Drivers (LongROAD) study, a prospective cohort of 2,990 older drivers (ages 65–79 at enrollment). The LongROAD study is a five-year multisite study and data collection ended October 31, 2022. Participants were recruited using a convenience sample from the health centers roster. The number of participants approached were 40,806 with 7.3% enrolling in the study. Sixty-one participants stopped driving permanently by year five and had data before and after DC. The PROMIS®-29 Adult Profile was utilized and includes: 1) Depression, 2) Anxiety, 3) Ability to Participate in Social Roles and Activities, 4) Physical Function, 5) Fatigue, 6) Pain Interference, 7) Sleep Disturbance, and 8) Numeric Pain Rating Scale.

Adjusted (age, education and gender) individual growth models with 2989 participants with up to six observations from baseline to year 5 in the models (ranging from n = 15,041 to 15,300) were utilized.

Results

Ability to participate in social roles and activities after DC improved overall. For those who volunteered, social roles and activities declined not supporting our hypothesis. For those who accessed alternative transportation, fatigue had an initial large increase immediately following DC thus not supporting our hypothesis. Urban residents had worse function and more symptoms after DC compared to rural residents (not supporting our hypothesis) except for social roles and activities that declined steeply (supporting our hypothesis).

Conclusions

Educating older adults that utilizing alternative transportation may cause initial fatigue after DC is recommended. Accessing alternative transportation to maintain social roles and activities is paramount for rural older adults after DC especially for older adults who like to volunteer.
The effectiveness of interventions to disseminate the results of non-commercial randomised clinical trials to healthcare professionals: a systematic review
Authors: South Annabelle , Bailey Julia V. , Parmar Mahesh K. B. , Vale Claire L.
Published: February 2024

Background

It is unclear how to disseminate the results of randomised controlled trials effectively to health professionals and policymakers to improve treatment, care or prevention through changing policy and practice. This systematic review examined the effectiveness of different methods of dissemination of clinical research results to professional audiences.

Methods

We systematically reviewed the published and grey literature from 2000 to 2022 for studies assessing different approaches for disseminating clinical study results to professional audiences (health professionals, policymakers and guideline developers). Two reviewers assessed potentially relevant full texts for inclusion. We grouped studies by intervention type, synthesising findings using effect direction plots. Outcomes were grouped into out-takes (e.g. awareness, knowledge, understanding), outcomes (e.g. attitude changes) and impact (changes in policy/practice). The quality of evidence was assessed using GRADE.

Results

Our search identified 13,264 unique records, of which 416 full texts were assessed for eligibility. Of 60 studies that were identified as eligible for inclusion, 20 evaluated the effectiveness of interventions to disseminate clinical research results (13 RCTs, 2 observational studies, 3 pre- and post-intervention surveys and 2 cross-sectional surveys). Studies were grouped by intervention: 7 studies that involved face-to-face meetings between the target audience and trained educators were classified as ‘outreach interventions’; 5 studies that provided a summary format for systematic review findings (e.g. summary of findings tables) were grouped together. There was high certainty evidence of a small beneficial impact of outreach interventions on health and moderate certainty evidence of impact on practice (mostly prescribing). There was no evidence of impact on policy and very low certainty around benefits on outcomes and out-takes. We found no consistent benefits of summary formats for systematic review results on outcomes or out-takes (moderate quality evidence). Other interventions with less evidence are reported in the Additional Materials.

Conclusions

Outreach interventions to disseminate clinical research results can lead to changes in practice and improvements in health. However, these interventions can be resource-intensive. Investment is vital to identify and implement effective and cost-effective ways to disseminate results, so that the potential benefits of trials to patients can be realised.

Trial registration

International Prospective Register of Systematic Reviews (PROSPERO), CRD42019137364.
Real-life impacts of olipudase alfa: The experience of patients and families taking an enzyme replacement therapy for acid sphingomyelinase deficiency
Authors: Raebel Eva M. , Wiseman Samantha , Donnelly Conan , Mathieson Toni , Pountney Jackson , Crowe Joslyn , Hopkin Justin
Published: February 2024

Background

Acid Sphingomyelinase Deficiency (ASMD) is an ultra-rare autosomal recessive lysosomal storage disorder characterized by intracellular lipid accumulation resulting from reduced function of acid sphingomyelinase. Olipudase alfa, an enzyme replacement therapy, was recently approved in several countries for the treatment of the non-neurologic manifestations of ASMD. Studies demonstrate improvement in organomegaly, pulmonary function and lipid profiles with olipudase alfa, yet little is known about its impact on quality of life (QoL) for patients and caregivers. The purpose of this study is to better understand the real-life impact of ASMD on patients and caregivers and assess how olipudase alfa impacts QoL for pediatric patients and their caregivers.

Methods

Caregivers of pediatric patients (≤ 18 years of age) with a confirmed diagnosis of ASMD that received olipudase alfa for at least 12 months were recruited in early 2022 through national patient organizations to participate in a global online questionnaire followed by semi-structured interviews. Ten caregivers of patients with ASMD who utilized olipudase alfa as an experimental therapy for pediatric patients participated in the study. Quantitative analysis of the results was undertaken, and qualitative data was analyzed using an inductive thematic approach.

Results

Ten eligible participants completed questionnaires, and 8 of the 10 went on to participate in structured interviews. Symptom burden of ASMD and impact on symptomatology and quality of life after olipudase alfa use are reported here. Five themes emerged from analysis: (1) ASMD is a systemic disease with a wide array of manifestations that significantly impact QoL; (2) Olipudase alfa was associated with improvements in all non-neurologic manifestations of ASMD; (3) Participants perceived the risk associated with olipudase alfa to be low and the benefits to greatly outweigh any risk or burden; (4) Participants reported an unmet need to treat the neurologic manifestations of the disease despite the benefits of olipudase alfa in the management of non-neurological symptoms; (5) Participants felt all patients with ASMD need access to olipudase alfa based on the life-changing experience they perceived.

Conclusions

These findings highlight the sustained positive impact olipudase alfa had in many domains that are deemed important to patients and families living with ASMD and outline the extensive unmet need for patients and families living with ASMD.
Not only vaccine hesitancy, but also vaccination campaign hesitancy drives measles epidemics in conflict-torn eastern DR Congo
Authors: Van Brusselen Daan , Dubois Ali Heshima , Bindu Lucien Kandundao , Moluh Zakari , Nzomukunda Yvonne , Liesenborghs Laurens
Published: February 2024

The COVID-19 pandemic and vaccine hesitancy are not the only causes of the increase in measles cases in low- and middle-income countries. Measles epidemics, like the recent one in eastern DRC, are often quickly halted by mass vaccination in ‘easy to reach’ refugee camps. However, governmental and humanitarian actors fail to respond effectively in ‘hard-to-reach’ areas like Masisi, frequently limiting themselves to more accessible areas close to big cities.
Blockage of mechanosensitive Piezo1 channel alleviates the severity of experimental malaria-associated acute lung injury
Authors: Zhang Min , Wang Qian Ru , Hou Xinpeng , Wang Qi , Yang Xiaoyan , Zhou Tingting , Liu Xiaobo , Wu Lirong , Wang Jie , Jin Xiaobao , Liu Zhenlong , Huang Bo
Published: February 2024

Background

Malaria-associated acute lung injury (MA-ALI) is a well-recognized clinical complication of severe, complicated malaria that is partly driven by sequestrations of infected red blood cells (iRBCs) on lung postcapillary induced impaired blood flow. In earlier studies the mechanosensitive Piezo1 channel emerged as a regulator of mechanical stimuli, but the function and underlying mechanism of Piezo1 impacting MA-ALI severity via sensing the impaired pulmonary blood flow are still not fully elucidated. Thus, the present study aimed to explore the role of Piezo1 in the severity of murine MA-ALI.

Methods

Here, we utilized a widely accepted murine model of MA-ALI using C57BL/6 mice with Plasmodium berghei ANKA infection and then added a Piezo1 inhibitor (GsMTx4) to the model. The iRBC-stimulated Raw264.7 macrophages in vitro were also targeted with GsMTx4 to further explore the potential mechanism.

Results

Our data showed an elevation in the expression of Piezo1 and number of Piezo1+-CD68+ macrophages in lung tissues of the experimental MA-ALI mice. Compared to the infected control mice, the blockage of Piezo1 with GsMTx4 dramatically improved the survival rate but decreased body weight loss, peripheral blood parasitemia/lung parasite burden, experimental cerebral malaria incidence, total protein concentrations in bronchoalveolar lavage fluid, lung wet/dry weight ratio, vascular leakage, pathological damage, apoptosis and number of CD68+ and CD86+ macrophages in lung tissues. This was accompanied by a dramatic increase in the number of CD206+ macrophages (M2-like subtype), upregulation of anti-inflammatory cytokines (e.g. IL-4 and IL-10) and downregulation of pro-inflammatory cytokines (e.g. TNF-α and IL-1β). In addition, GsMTx4 treatment remarkably decreased pulmonary intracellular iron accumulation, protein level of 4-HNE (an activator of ferroptosis) and the number of CD68+-Piezo1+ and CD68+-4-HNE+ macrophages but significantly increased protein levels of GPX4 (an inhibitor of ferroptosis) in experimental MA-ALI mice. Similarly, in vitro study showed that the administration of GsMTx4 led to a remarkable elevation in the mRNA levels of CD206, IL-4, IL-10 and GPX-4 but to a substantial decline in CD86, TNF-α, IL-1β and 4-HNE in the iRBC-stimulated Raw264.7 cells.

Conclusions

Our findings indicated that blockage of Piezo1 with GsMTx4 alleviated the severity of experimental MA-ALI in mice partly by triggering pulmonary macrophage M2 polarization and subsequent anti-inflammatory responses but inhibited apoptosis and ferroptosis in lung tissue. Our data suggested that targeting Piezo1 in macrophages could be a promising therapeutic strategy for treating MA-ALI.

Graphical Abstract
Identification of DNA methylation biomarkers for evaluating cardiovascular disease risk from epigenome profiles altered by low-dose ionizing radiation
Authors: Park Jihye , Lee Hae-June , Han Yu Kyeong , Kang Keunsoo , Yi Joo Mi
Published: February 2024

Background

Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that such radiation can induce epigenetic changes. Nevertheless, whether exposure to low-dose radiation can disrupt endothelial cell function at the molecular level is unclear. Because endothelial cells play crucial roles in cardiovascular health and disease, we aimed to investigate whether low-dose radiation could lead to differential DNA methylation patterns at the genomic level in endothelial cell (EC) lines.

Methods

We screened for changes in DNA methylation patterns in primary human aortic (HAECs) and coronary artery endothelial cells following exposure to low-dose ionizing radiation. Using a subset of genes altered via DNA methylation by low-dose irradiation, we performed gene ontology (GO) analysis to predict the possible biological network mediating the effect of low-dose radiation. In addition, we performed comprehensive validation using methylation and gene expression analyses, and ChIP assay to identify useful biomarkers among candidate genes for use in detecting low-dose radiation exposure in human primary normal ECs.

Results

Low-dose radiation is sufficient to induce global DNA methylation alterations in normal EC lines. GO analysis demonstrated that these hyper- or hypo-methylated genes were linked to diverse biological pathways. Our findings indicated a robust correlation between promoter hypermethylation and transcriptional downregulation of four genes (PGRMC1, UNC119B, RERE, and FNDC3B) in response to low-dose ionizing radiation in HAECs.

Conclusions

Based on these findings, the identified genes can serve as potential DNA methylation biomarkers for the assessment of cardiovascular risk upon exposure to low-dose radiation.
The Cambrian fossil Pikaia, and the origin of chordate somites
Authors: Lacalli Thurston
Published: February 2024

The Middle Cambrian fossil Pikaia has a regular series of vertical bands that, assuming chordate affinities, can be interpreted as septa positioned between serial myotomes. Whether Pikaia has a notochord and nerve cord is less certain, as the dorsal organ, which has no obvious counterpart in living chordates, is the only clearly defined axial structure extending the length of the body. Without a notochord to serve as a reference point, the location of the nerve cord is then conjectural, which begs the question of how a dorsal neural center devoted to somite innervation would first have arisen from a more diffuse ancestral plexus of intraepithelial nerves. This question is examined using hemichordates as a reference point, first for the information they provide on the organization of the ancestral deuterostome nervous system, and second, extending the analysis of E. E. Ruppert, to explain why neural infoldings like the enteropneust collar cord would first have evolved. Both implicate the medial surface of the anterior-most part of the metacoel as the likely site for the evolution of the first somites. The analysis highlights the importance of the somatobranchial condition in chordates, meaning the linkage between the anterior trunk, hox1 expression, and the beginning of the gill series and somites. This feature is arguably a valid criterion by which to assess extinct taxa from the Cambrian that resemble chordates (e.g., vetulicolians and yunnanozoans), but may be unrelated to them. In a more speculative vein, the nature of the dorsal organ is discussed, including the possibility that it is an expanded neural tube combining neural and support functions in one structure.
Chronic disease and multimorbidity in the Chinese older adults’ population and their impact on daily living ability: a cross-sectional study of the Chinese Longitudinal Healthy Longevity Survey (CLHLS)
Authors: Chen Ye , Ji Huixia , Shen Yang , Liu Dandan
Published: February 2024

Background

Owing to an increase in life expectancy, it is common for the older adults to suffer from chronic diseases that can result in disability and a low quality of life. This study aimed to explore the influence of chronic diseases and multimorbidities on activities of daily living (ADLs) and instrumental ADLs (IADLs) in an older Chinese population.

Methods

Based on the Chinese Longitudinal Healthy Longevity Survey (2018), 9,155 older adults aged 65 years and above were included in the study. A self-administered questionnaire was used to collect information on demographic characteristics, chronic diseases, ADLs, and IADLs. The impact of factors affecting ADL and IADL impairment in older adults was analysed using binary logistic regression.

Results

In total, 66.3% participants had chronic diseases. Hypertension, heart disease, arthritis, diabetes and cerebrovascular disease were among the top chronic diseases. Of these, 33.7% participants had multimorbidities. The most common combination of the two chronic diseases was hypertension and heart disease (11.2%), whereas the most common combination of the three chronic diseases was hypertension, heart disease, and diabetes (3.18%). After categorising the older adults into four age groups, dementia, visual impairment, and hearing impairment were found to be more prevalent with increasing age. The prevalence of hypertension, heart disease, cerebrovascular disease, gastrointestinal ulcers, arthritis and chronic nephritis gradually increased with age until the age of 75 years, peaked in the 75–84 years age group, and then showed a decreasing trend with age. Multimorbidity prevalence followed a similar pattern. Regression analysis indicated that the increase in age group and the number of chronic diseases independently correlated with impairments in ADL as well as IADL. Additionally, gender, physical activity, educational background, obesity, depressive symptoms, and falls also had an impact on ADLs or IADLs.

Conclusion

Chronic diseases and multimorbidities are common in older adults, and it is important to note that aging, multimorbidity, obesity, and unhealthy lifestyle choices may interfere with ADLs or IADLs in older adults. Therefore, it is imperative that primary healthcare providers pay special attention to older adults and improve screening for multimorbidity and follow-up needs.
Lung function and the risk of frailty in the European population: a mendelian randomization study
Authors: Zhou Rong , Tian Ge , Guo Xingzhi , Li Rui
Published: February 2024

Background

Epidemiological evidence has suggested a relationship between lung function and frailty, but the precise nature of the causality remains unclear. In this study, we applied a two-sample Mendelian randomization (MR) analysis to determine the causal effects of lung function on frailty.

Methods

Single nucleotide polymorphisms (SNPs) independently related (P ≤ 5E−08) to lung function, as identified by genome-wide association study (GWAS), were applied as instrumental variables (IV). The association with frailty index (FI) was investigated using summary-level data from the latest GWAS on FI (n = 175,226). Different statistical methods were employed to evaluate the causal estimates between lung function and FI. The pleiotropy, heterogeneity, and leave-one-out analysis were applied to confirm the stability of the MR estimates.

Results

Using the random-effect inverse-variance weighted approach, genetically proxied forced expiratory volume in the first second (FEV1), ratio of FEV1 on forced vital capacity (FVC) [FEV1/FVC], and peak expiratory flow (PEF) were significantly and inversely associated with FI (FEV1, β = −0.08, P = 2.03E−05; FEV1/FVC, β = −0.06, P = 9.51E−06; PEF, β = −0.07, P = 4.09E−04) with good statistical power (99.7–100%). However, no significant association was observed between FVC and FI (β = −0.01, P = 0.681). Leave-one-out analysis showed that there was no single SNP driving the bias of the estimates. There was potential heterogeneity, but no obvious pleiotropy was founded in this MR study.

Conclusions

Our findings indicate that impaired pulmonary function is closely related to the risk of frailty. Enhancing lung function in the elderly population may contribute to the prevention of frailty to a certain extent.
Drug-drug interaction assessment based on a large-scale spontaneous reporting system for hepato- and renal-toxicity, and thrombocytopenia with concomitant low-dose methotrexate and analgesics use
Authors: Honma Takeshi , Onda Kenji , Masuyama Koichi
Published: February 2024

Background

Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment and is highly effective with low-dose intermittent administration. MTX is occasionally used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP)/paracetamol for pain or inflammation control. With MTX treatment, the side effects, such as hepatotoxicity, renal failure, and myelosuppression should be considered. These are also seen with analgesics treatment.

Methods

We used a large spontaneously reported adverse event database (FAERS [JAPIC AERS]) to analyze whether the reporting of adverse events increased upon MTX and analgesic therapy in patients with RA.

Results

After identifying RA cases, the crude reporting odds ratios (cRORs) for hepatotoxicity, renal failure, and thrombocytopenia associated with the use of MTX, APAP, or NSAIDs were calculated by disproportionality analysis, which revealed significantly higher cRORs for these events. No analgesics showed consistent positive signals for drug-drug interaction (DDI) with concomitant low-dose MTX analyzed using four algorithms for DDI interaction (the Ω shrinkage measure, additive or multiplicative, and combination risk ratio models). However, in renal failure and thrombocytopenia, loxoprofen (Ω025 = 0.08) and piroxicam (Ω025 = 0.46), and ibuprofen (Ω025 = 0.74) and ketorolac (Ω025 = 3.52), respectively, showed positive signals in the Ω shrinkage measure model, and no consistency was found among adverse events or NSAIDs.

Conclusions

Studies using spontaneous reporting systems have limitations such as reporting bias or lack of patient background; however, the results of our comprehensive analysis support the results of previous clinical or epidemiological studies. This study also demonstrated the usefulness of FAERS for DDI assessment.
A HBIM pipeline for the conservation of large-scale architectural heritage: the city Walls of Pisa
Authors: Giuliani Francesca , Gaglio Francesca , Martino Massimiliano , De Falco Anna
Published: February 2024

In the architectural heritage field, a complete and in-depth knowledge of the assets is indispensable for any restoration and conservation strategy. In this context, the Historical Building Information Modelling (HBIM) technique is gaining much interest in supporting the diagnostic phase and the design and management of conservation activities. The HBIM provides opportunities to collect, organize and integrate information coming from different sources, inspections, and diagnosis techniques as well as to use standardized and effective tools for orienting cultural heritage asset management. This study addresses the challenges of developing HBIM for large-scale assets, that require adapting the conventional workflow to deliver results in a reasonable time. To this aim, a novel procedure involving a fit-for-purpose Inventory form and a scan-to-BIM approach is proposed. The data acquisition process is speeded up using multiple surveying techniques, and the modelling and information phases benefit from the interoperability among different tools that are already known by professionals in the field. As such, the main innovation lies in the ability to oversee the entire process through a single software, ensuring centralized and efficient control. This innovative process has been applied to investigate a significant portion of the city walls of Pisa, proving its ability to support the decision-making phase for planned conservation of large-scale architectural heritage. The emphasis is on the all-encompassing, interdisciplinary understanding of the assets across different scales. The suggested approach ensures a swift yet precise and reliable outcome in the diagnostic process and facilitating the critical temporal assessments and the review of information by any actor involved in the conservation.
CDK4/6 inhibitor-induced bone marrow micronuclei might be caused by cell cycle arrest during erythropoiesis
Authors: Okada Yuki , Chikura Satsuki , Kimoto Takafumi , Iijima Takeshi
Published: February 2024

Background

A micronucleus test is generally used to evaluate the genotoxic potential of chemicals. Exaggerated erythropoiesis, as occurs following bleeding, may induce an unexpected increase in micronucleus frequency. This false positive result would be typical in a genotoxicity study due to the enhanced progression of the cell cycle that restores decreased blood cells. The cyclin-dependent kinase (CDK) family is known to play an essential role in preventing genomic instability. Conversely, a selective CDK4/6 inhibitor PD0332991, clinically named Palbociclib, is reported to have genotoxic potential, shown by positive results in both in vitro and in vivo micronucleus studies. To clarify the mechanism by which cell cycle arrest induced by a CDK4/6 inhibitor increases micronucleus frequency, we investigated the positive results of the bone marrow micronucleus test conducted with PD0332991.

Results

Rats treated with PD0332991 exhibited increased micronucleus frequency in an in vivo bone marrow micronucleus test whereas it was not increased by treatment in human lymphoblastoid TK6 cells. In addition, all other genotoxicity tests including the Ames test and the comet assay showed negative results with PD0332991. Interestingly, PD0332991 treatment led to an increase in erythrocyte size in rats and affected the size distribution of erythrocytes, including the micronucleus. The mean corpuscular volume of reticulocytes (MCVr) in the PD0332991 treatment group was significantly increased compared to that of the vehicle control (83.8 fL in the PD0332991, and 71.6 fL in the vehicle control.). Further, the average micronucleated erythrocytes (MNE) size of the PD0332991 group and vehicle control was 8.2 and 7.3 µm, respectively. In the histogram, the vehicle control showed a monomodal distribution with a peak near 7.3 µm. In contrast, the PD0332991 group showed a bimodal distribution with peaks around 7.5 and 8.5 µm. Micronucleated erythrocytes in the PD0332991 group were significantly larger than those in the vehicle control.

These results suggest that the increase in micronucleus frequency induced by the CDK4/6 inhibitor is not due to genotoxicity, but is attributable to disturbance of the cell cycle, differentiation, and enucleation of erythroblasts.

Conclusions

It was suggested that the positive outcome of the in vivo bone marrow micronucleus test resulting from treatment with PD0332991 could not be attributed to its genotoxicity. Further studies to clarify the mechanism of action can contribute to the development of drug candidate compounds lacking intrinsic genotoxic effects.
CT-GCN+: a high-performance cryptocurrency transaction graph convolutional model for phishing node classification
Authors: Fu Bingxue , Wang Yixuan , Feng Tao
Published: February 2024

Due to the anonymous and contract transfer nature of blockchain cryptocurrencies, they are susceptible to fraudulent incidents such as phishing. This poses a threat to the property security of users and hinders the healthy development of the entire blockchain community. While numerous studies have been conducted on identifying cryptocurrency phishing users, there is a lack of research that integrates class imbalance and transaction time characteristics. This paper introduces a novel graph neural network-based account identification model called CT-GCN+, which utilizes blockchain cryptocurrency phishing data. It incorporates an imbalanced data processing module for graphs to consider cryptocurrency transaction time. The model initially extracts time characteristics from the transaction graph using LSTM and Attention mechanisms. These time characteristics are then fused with underlying features, which are subsequently inputted into a combined SMOTE and GCN model for phishing user classification. Experimental results demonstrate that the CT-GCN+ model achieves a phishing user identification accuracy of 97.22% and a phishing user identification area under the curve of 96.67%. This paper presents a valuable approach to phishing detection research within the blockchain and cryptocurrency ecosystems.
Alternating hemiplegia of childhood misdiagnosed as hysteria: a case report
Authors: Wei Danlei , Lv Kang , He Jialinzi , Xiao Bo , Long Lili
Published: February 2024

Background

Alternating hemiplegia of childhood (AHC) is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia, and frequently accompanied by dystonic posturing, choreoathetosis movements, anomalous ocular motions, and a gradual deterioration in cognitive function. The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.

Case presentation

Here, we report a 16-year-old girl with recurrent hemiplegia since her infancy. This patient has experienced paroxysmal limb weakness and aphasia for over 15 years, and has kept seeking medical attention but without receiving effective treatment. A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital. Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C (p.Leu757Pro) mutation in her ATP1A3 gene. Notably, her clinical manifestations, including pathological emotional responses and autonomic dysfunction, differed from the established profile associated with the same ATP1A3 mutation, which typically present with intellectual disability, a rostrocaudal symptom gradient, choreoathetosis, and dysarthria. The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.

Conclusions

This case enhances our understanding of the intricate clinical manifestations of AHC, which require careful differentiation from various diseases such as epilepsy, hysteria, and paroxysmal dyskinesias. In the diagnosis of patients presenting with suspected symptoms, adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments. Additionally, when AHC is suspected in a patient, genetic testing should be considered as part of the diagnostic approach.
Quantitative seismic fracture characterization of a sandstone reservoir — Decatur, Illinois Basin
Authors: Chaudhuri Debasis , Roy Ankur
Published: February 2024

The Illinois Basin Decatur Project, a carbon capture and sequestration task, was undertaken to sequester 1 million tonnes of CO2 into a sandstone reservoir. A 3D seismic survey was conducted to characterize the reservoir. A geomodel was developed from seismic data, inversion results, and well data to geostatistically map the storage potential of the reservoir. However, no fracture model was created or utilized in this exercise. Fractures inherently influence the porosity and permeability of a reservoir. Ignoring them in reservoir characterization is not an optimal reservoir management practice. The image-log interpretation from a few vertical wells drilled in the area shows the bedding plane dips, but no fracture has been identified. However, the lack of fracture crossings in a few vertical wells does not imply that a formation is devoid of fractures altogether. Hence, seismic fracture characterization (leveraging the dense 3D seismic data) is necessary for a reservoir characterization exercise. We utilized the publicly available Decatur 3D seismic data set to run a seismic fracture characterization workflow to delineate potential fracture corridors present in the reservoir. We calculated three edge detection attributes (structural tensor, structure-oriented semblance, and structural dip) in combination to delineate the fracture lineaments. Our workflow extracts several quantitative measures of the seismic lineaments such as dip, azimuth, area, and length, which can be analyzed statistically. The principal focus of this work is to find a way forward to integrate the fractures from seismic data in a geologic model that can be utilized in simulations. Based on our interpretation of seismic fractures, we created a discrete fracture network that can be a building block for creating a finer-resolution fracture model. We also explored the fractal characteristics of seismic-derived fracture lineaments as a way forward for generating discrete fracture networks.
Reviews
Authors: Aitken Julie
Published: February 2024

Mission Earth: Geodynamics and Climate Change Observed Through Satellite Geodesy, by D. Angermann, R. Pail, F. Seitz, and U. Hugentobler, 2022.
Co-design of ‘Ways of Being’, a web-based experience to optimise online arts and culture for mental health in young people
Authors: Syed Sheriff Rebecca J. , Sinclair Eloise , Young Jen , Bhamra Sophia , Chandler Louise , Arachchige Tharuka , Adams Helen , Bonsaver Laura , Riga Evgenia , Bergin Laura , Mirtorabi Negin , Abuelgasim Leenah , Beuchner Hadassah , Geddes John
Published: February 2024

Aims and method

We aimed to co-design an intervention optimising the benefits of online arts and culture for mental health in young people for subsequent testing in a trial. Co-design followed the double diamond phases of design, discover, define, develop and deliver.

Results

Navigating the views of all co-designers to produce a testable resource demanded in-depth understanding, and frequent iterations in multiple modalities of the theoretical basis of the intervention, amplification of youth voice and commitment to a common goal.

Clinical implications

Co-design with a broad range of collaborators with a shared vision was valued by young co-designers and produced an effective intervention. Co-design allowed the theoretical basis to be followed and refined to create an engaging, practical and testable web experience, aiming to optimise the mental health benefits of online arts and culture for young people in a randomised controlled trial.