bluuebunny/crossref_metadata_2025 huggingface dataset:
Geochemistry, petrogenesis and geological implication of granitic rocks in Igarra area, southwestern Nigeria
Authors: Oyebamiji Abiola , Akinola Oluwatoyin , Olaolorun Olusola , Abdu-Raheem Yusuf , Adeoye Aderemi , Oguntuase Mary
Published: August 2024

The Igarra area in southwestern Nigeria hosts a diverse suite of granitic rocks that play a significant role in understanding the regional geological framework. This study employs a comprehensive geochemical and petrogenetic approach to unravel these granitic rock’s origin, evolution and geological implications. A comprehensive geochemical analysis was conducted on samples of the granitoids. The results showed moderate to high SiO2, Na2O and K2O, with average compositions of 68.95%, 3.50% and 4.09%, respectively. The total alkalis are characterised by low MgO, CaO, TiO2 and P2O5, consistent with metaluminous to weak peraluminous compositions. The granite primarily falls within the high-K calc-alkaline region, exhibiting distinctive patterns in rare earth elements, with notable depletion in Nb, P and Ti. Geochemical modelling suggests that the granitoids originated from incomplete melting of metasedimentary source rocks under low to moderate pressure conditions, with limited crustal contamination. Trace element discrimination diagrams indicate a collisional tectonic setting for the Igarra granitoids, interpreted to have formed during continental collision. This mixed-source model suggests a complex magmatic system involving both crustal and mantle contributions, with potential interaction between these diverse melt components during the formation of the granites. This study offers fresh perspectives on the evolutional setting of the Igarra granitoids, understanding the geological effect of the Pan-African belt in Southwestern Nigeria and its broader implications.
Kick-starting an Innovation Ecosystem
Authors: Meyer Arnoud De , Williamson Peter J.
Published: August 2024

Do you believe that innovation ecosystems are valuable but don’t know how to start or build them? Arnoud De Meyer and Peter J. Williamson tell you how to do it.
How Modern Tech Companies Differ from the Twentieth Century's Industrial Giants
Authors: Govindarajan Vijay , Srivastava Anup
Published: August 2024

Vijay Govindarajan and Anup Srivastava describe six factors that differentiate today’s corporate technology giants from those of the twentieth century, illustrating why professionals should appreciate these differences.
Prevalence of Tobacco Products’ Use and Associated Factors Among Adolescents in Morocco: A Systematic Review
Authors: MOUTAWAKKIL Salma Ghofrane , EL-AMMARI Abdelfettah , EL MALKI Hicham , RAGALA Mohammed El Amine , EL RHAZI Karima , ZARROUQ Btissame
Published: August 2024

Introduction:

Tobacco use is the major preventable cause of premature death worldwide, responsible for about 8 million deaths per year, mostly in low- and middle-income countries, such as Morocco. Adolescents’ tobacco use is a matter of concern, because early initiation increases the risk of becoming a lifelong user. There exists a notable gap in the synthesis of evidence concerning tobacco use among Moroccan adolescents. Thus, the purpose of this study was to provide a comprehensive view of the prevalence of tobacco products’ use and associated factors among adolescents in Morocco.

Methods:

We systematically searched PubMed, Scopus, Web of Science and ScienceDirect for relevant studies reporting prevalence rates of tobacco products’ use among Moroccan adolescents, published until June 2024, using inclusion and exclusion criteria in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Additional searches were completed on other sources to reach unpublished reports. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the quality of included studies.

Results:

After the final screening, 22 papers met the inclusion criteria. Life-time prevalence of tobacco use ranged from 7.8% to 20.4% for cigarettes smoking, from 10.6% to 21.9% for waterpipe, from 7.9% to 9.1% for chewing tobacco and from 9.2% to 12.4% for snuff. The last 12-month prevalence of cigarette smoking was comprised between 6.9% and 10.8%. As for the prevalence of current use, ranges of (1.8%-16.4%) and (4.9%-8.4%) were noted for cigarettes and waterpipe, respectively. The most commonly highlighted risk factors for tobacco use included male sex, older age, having friends or family members who use tobacco and low perception of risk associated with tobacco use.

Conclusion:

Our findings reveal an alarming situation of tobacco use among Moroccan adolescents. Therefore, it is crucial that all stakeholders engage in concerted efforts to develop and implement evidence-based preventive interventions among early adolescents.
The silent epidemic: exploring the link between loneliness and chronic diseases in China’s elderly
Authors: Meng Lingbing , Xu Ruofan , Li Jianyi , Hu Jiabin , Xu Hongxuan , Wu Dishan , Hu Xing , Zeng Xuezhai , Zhang Qiuxia , Li Juan , Liu Deping
Published: August 2024

Background

Chronic diseases, such as heart disease, cancer, and diabetes, are the leading causes of death and disability. Loneliness is linked to a greater risk of chronic disease. However, the lack of loneliness may change this relationship.

Methods

The 4th Survey of the Aged Population in Urban and Rural China (SSAPUR) was performed. 222,179 people over 60 years old were recruited. Chronic disease was defined by self-reported tumble incidents using the fourth SSAPUR questionnaire. We found that the residuals were well normally distributed. Subsequently, we analyzed the association between each studied factor and chronic disease by univariate logistic regression analysis. Finally, we stratified the population by age, gender, and urban and rural.

Results

77,448 individuals experienced loneliness, while 137,593 did not. Loneliness correlated significantly with urban-rural classification, age, and gender (P < 0.001). There was a significant association between chronic diseases and loneliness (P < 0.05). Compared to lonely individuals, those with low level of loneliness had a lower incidence of gastric diseases (OR = 0.752, 95% CI, 0.736–0.769, P < 0.001), osteoarthritis (OR = 0.685, 95% CI, 0.673–0.697, P < 0.001), chronic obstructive pulmonary disease (COPD) (OR = 0.678, 95% CI, 0.659–0.698, P < 0.001), asthma (OR = 0.608, 95% CI, 0.583–0.633, P < 0.001), malignant tumors (OR = 0.892, 95% CI, 0.822–0.968, P = 0.006), and reproductive system diseases (OR = 0.871, 95% CI, 0.826–0.918, P < 0.001).

Conclusion

In summary, loneliness is an important risk factor in the occurrence and development of chronic diseases in the elderly in China, and it has adverse effects on hypertension, stomach disease, cataract or glaucoma, osteoarthrosis, chronic lung disease, asthma, malignant tumor, and reproductive system diseases.
Monitoring the VDPV2 outbreak in Egypt during 2020–2021 highlights the crucial role of environmental surveillance and boosting immunization in combating Poliovirus
Authors: Shabana Menna R. , Zaghloul Amira Y. , El Shaarawy Tamer H. , Elleboudy Nooran S. , Aboshanab Khaled M.
Published: August 2024

Background

Poliovirus is a highly infectious enterovirus (EV) that primarily affects children and can lead to lifelong paralysis or even death. Vaccine-derived polioviruses (VDPVs) are a great threat since they are derived from the attenuated virus in the Oral Poliovirus Vaccine (OPV) and can mutate to a more virulent form. The purpose of this study was to identify VDPV serotype 2 through the year 2020–2021 via surveillance of sewage samples collected from different localities and governorates in Egypt and stool specimens from Acute Flaccid Paralysis (AFP) cases. Both were collected through the national poliovirus surveillance system and according to the guidelines recommended by the WHO.

Methods

A total of 1266 sewage samples and 3241 stool samples from January 2020 to December 2021 were investigated in the lab according to World Health Organization (WHO) protocol for the presence of Polioviruses by cell culture, molecular identification of positive isolates on L20B cell line was carried out using real-time polymerase chain reactions (RT-PCR). Any positive isolates for Poliovirus type 2 and isolates suspected of Vaccine Derived Poliovirus Type 1 and type 3 screened by (VDPV1) or Vaccine Poliovirus Type 3 (VDPV3) assay in RT-PCR were referred for VP1 genetic sequencing.

Results

The outbreak was caused by circulating VDPV2 (cVDPV2) strains started in January 2021. By the end of February 2021, a total of 11 cVDPV2s were detected in sewage samples from six governorates confirming the outbreak situation. One additional cVDPV2 was detected later in the sewage sample from Qena (June 2021). The first and only re-emergence of VDPV2 in stool samples during the outbreak was in contact with Luxor in June 2021. By November 2021, a total of 80 VDPVs were detected. The Egyptian Ministry of Health and Population (MOHP), in collaboration with the WHO, responded quickly by launching two massive vaccination campaigns targeting children under the age of five. Additionally, surveillance systems were strengthened to detect new cases and prevent further spread of the virus.

Conclusion

The continued threat of poliovirus and VDPVs requires ongoing efforts to prevent their emergence and spread. Strategies such as improving immunization coverage, using genetically stable vaccines, and establishing surveillance systems are critical to achieving global eradication of poliovirus and efficient monitoring of VDPVs outbreaks.
Association of monoaminergic gene polymorphisms in chronic inflammatory pulmonary disease patients with successful smoking cessation
Authors: Mikaczo Angela , Papp Csaba , Erdei Tamas , Posa Aniko , Zahuczky Gabor , Varga Csaba , Szabo Janos , Gesztelyi Rudolf , Szilasi Maria , Zsuga Judit
Published: August 2024

Background

Albeit smoking cessation has unequivocal health benefits, attempts to quit are not unanimous, even in patient populations at high risk for smoking-related diseases cessation. Allelic variations of enzymes involved in dopamine metabolism are being considered as candidates for nicotine addiction. We set out to assess whether rs4680 G/A and rs2235186 G/A polymorphisms of COMT and MAO-A, respectively are associated with the ability to quit smoking in chronic inflammatory pulmonary disease patients.

Methods

Patients managed for chronic inflammatory pulmonary disease by the Department of Pulmonology (University of Debrecen, Hungary), with a current or past smoking habit were included in the current analysis. The study was designed in line with the STROBE statement for cross-sectional studies and was approved by the National Center for Public Health, Hungary. Genomic DNA was extracted from peripheral blood specimens. SNPs were genotyped using TaqMan SNP genotyping assays.

Results

rs4680 COMT polymorphism showed significant effect for successful smoking cessation in patients with pulmonary disease. Accordingly, A/A subjects had lower odds for successful smoking cessation (odds ratio 0.37; 95% confidence interval 0.20–0.69, p = 0.002 (additive model). On the other hand, patients homozygous for the minor allele (A) at rs2235186 of MAO-A showed a non-significant trend toward increased odds for successful smoking cessation.

Conclusions

The presence of the minor allele for rs4680 COMT was shown to decrease the odds for successful smoking cessation, a finding that may be interpreted in view of the altered balance between tonic and phasic dopamine release.
Leveraging implementation science theories to develop and expand the use of a penicillin allergy de-labeling intervention
Authors: Alagoz Esra , Saucke Megan , Balasubramanian Prakash , Liebenstein Tyler , Kakumanu Sujani
Published: August 2024

Background

Penicillin allergy is the most frequently reported drug allergy, yet most patients can tolerate the drug if challenged. Despite this discrepancy, large scale penicillin allergy de-labeling interventions have not been widely implemented in many health care systems. The application of a multi-method implementation science approach can provide key tools to study this evidence to practice gap and provide insight to successfully operationalize penicillin allergy evaluation in real-world clinical settings.

Methods

We followed a four-step process that leverages qualitative analysis to design evidence-based, actionable strategies to develop an intervention. First, we specified the clinician-perceived barriers to penicillin allergy de-labeling (intervention targets). We then mapped intervention targets onto Theoretical Domains Framework (domains and constructs) and found the root causes of behavior. Next, we linked root causes of behavior with intervention functions (BCW). In the final step, we synthesized participants’ suggestions for process improvement with implementation strategies aligning with the intervention functions.

Results

Evidence-based strategies such as focused education and training in penicillin allergy evaluation can address knowledge and confidence barriers reported by frontline clinicians. Other key strategies involve developing a system of champions, improving communications systems, and restructuring the healthcare team. Implementation mapping can provide a powerful multi-method framework to study, design, and customize intervention strategies. Conclusion: Empowering clinicians beyond allergy specialists to conduct penicillin allergy assessments requires designing new workflows and systems and providing additional knowledge to those clinicians.
No evidence that ACE2 or TMPRSS2 drive population disparity in COVID risks
Authors: Pearson Nathaniel M. , Novembre John
Published: August 2024

Early in the SARS-CoV2 pandemic, in this journal, Hou et al. (BMC Med 18:216, 2020) interpreted public genotype data, run through functional prediction tools, as suggesting that members of particular human populations carry potentially COVID-risk-increasing variants in genes ACE2 and TMPRSS2 far more often than do members of other populations. Beyond resting on predictions rather than clinical outcomes, and focusing on variants too rare to typify population members even jointly, their claim mistook a well known artifact (that large samples reveal more of a population’s variants than do small samples) as if showing real and congruent population differences for the two genes, rather than lopsided population sampling in their shared source data. We explain that artifact, and contrast it with empirical findings, now ample, that other loci shape personal COVID risks far more significantly than do ACE2 and TMPRSS2—and that variation in ACE2 and TMPRSS2 per se unlikely exacerbates any net population disparity in the effects of such more risk-informative loci.
Adulthood weight changes, body mass index in youth, genetic susceptibility and risk of atrial fibrillation: a population-based cohort study
Authors: Du Yufeng , Qi Lu , Borné Yan , Sonestedt Emily
Published: August 2024

Background

Epidemiological evidence on weight change and atrial fibrillation (AF) remains limited and inconsistent. Previous studies on body mass index (BMI) in youth and AF rarely considered subsequent BMI. This study aimed to assess the associations of AF with weight change and BMI in youth, as well as modified effect by genetic susceptibility of AF.

Methods

The study included 21,761 individuals (mean age 57.8 years) from the Malmö Diet and Cancer cohort. Weight information was obtained at three time points, including recalled weight at age 20 years, measured weight at baseline (middle adulthood), and reported weight at 5-year follow-up examination (late middle adulthood). A weighted genetic risk score of AF was created using 134 variants.

Results

During a median follow-up of 23.2 years, a total of 4038 participants developed AF. The association between weight change from early to middle adulthood and AF risk was modified by sex (Pinteraction = 0.004); weight loss was associated with a lower AF risk in females, but not in males. Conversely, weight gain was positively associated with AF risk in a linear manner in females, whereas increased AF risk appeared only when weight gain exceeded a threshold in males. Participants with weight gain of > 5 kg from middle to late middle adulthood had a 19% higher risk of AF relative to those with stable weight, whereas weight loss showed a null association. Compared to individuals with a lower BMI at age 20 years, those with a BMI above 25 kg/m2 had an increased risk of AF (HR = 1.14; 95% CI: 1.02–1.28), after controlling for baseline BMI; this association was more pronounced in males or those with a lower genetic risk of AF.

Conclusions

Weight gain in middle adulthood was associated with higher AF risk. Weight loss from early to middle adulthood, but not from middle to late middle adulthood, was associated with a lower risk of AF only in females. Higher BMI in youth was associated with an increased risk of AF, particularly among males or those with a lower genetic risk of AF.
Access to community-based eye services in Meru, Kenya: a cross-sectional equity analysis
Authors: Allen Luke N , Karanja Sarah , Gichangi Michael , Bunywera Cosmas , Rono Hillary , Macleod David , Kim Min Jung , Tlhajoane Malebogo , Burton Matthew J. , Ramke Jacqueline , Bolster Nigel M. , Bastawrous Andrew
Published: August 2024

Background

Over 80% of blindness in Kenya is due to curable or preventable causes and 7.5 m Kenyans currently need eye services. Embedding sociodemographic data collection into screening programmes could help identify the groups facing systematic barriers to care. We aimed to determine the sociodemographic characteristics that were associated with access among patients diagnosed with an eye problem and referred for treatment in the Vision Impact Programme, currently operating in Meru County.

Method

We used an embedded, pragmatic, cross-sectional design. A list of sociodemographic questions was developed with input from key stakeholders. The final question set included the following domains: age, gender, religion, marital status, disability, education, occupation, income, housing, assets, and health insurance. These were integrated into an app that is used to screen, refer, and check-in (register) participants within a major eye screening programme. We gathered data from 4,240 people who screened positive and were referred to their local outreach treatment clinic. We used logistic regression to identify which groups were facing the greatest barriers to accessing care.

Results

A quarter of those screened between April – July 2023 were found to have an eye problem and were referred, however only 46% of these people were able to access care. In our fully adjusted model, at the 0.05 level there were no statistically significant differences in the odds of attendance within the domains of disability, health insurance, housing, income, or religion. Strong evidence (p < 0.001) was found of an association between access and age, gender, and occupation; with males, younger adults, and those working in sales, services and manual jobs the least likely to receive care.

Conclusions

Access to essential eye services is low and unequal in Meru, with less than a third of those aged 18–44 receiving the care they need. Future work should explore the specific barriers faced by this group.
Older adults’ compliance with mobile ecological momentary assessments in behavioral nutrition and physical activity research: pooled results of four intensive longitudinal studies and recommendations for future research
Authors: Compernolle Sofie , Vetrovsky T. , Maes I. , Delobelle J. , Lebuf E. , De Vylder F. , Cnudde K. , Van Cauwenberg J. , Poppe L. , Van Dyck D.
Published: August 2024

Background

Mobile Ecological Momentary Assessment (EMA) is increasingly used to gather intensive, longitudinal data on behavioral nutrition, physical activity and sedentary behavior and their underlying determinants. However, a relevant concern is the risk of non-random non-compliance with mobile EMA protocols, especially in older adults. This study aimed to examine older adults’ compliance with mobile EMA in health behavior studies according to participant characteristics, and prompt timing, and to provide recommendations for future EMA research.

Methods

Data of four intensive longitudinal observational studies employing mobile EMA to understand health behavior, involving 271 community-dwelling older adults (M = 71.8 years, SD = 6.8; 52% female) in Flanders, were pooled. EMA questionnaires were prompted by a smartphone application during specific time slots or events. Data on compliance (i.e. information whether a participant answered at least one item following the prompt), time slot (morning, afternoon or evening) and day (week or weekend day) of each prompt were extracted from the EMA applications. Participant characteristics, including demographics, body mass index, and smartphone ownership, were collected via self-report. Descriptive statistics of compliance were computed, and logistic mixed models were run to examine inter- and intrapersonal variability in compliance.

Results

EMA compliance averaged 77.5%, varying from 70.0 to 86.1% across studies. Compliance differed among subgroups and throughout the day. Age was associated with lower compliance (OR = 0.96, 95%CI = 0.93–0.99), while marital/cohabiting status and smartphone ownership were associated with higher compliance (OR = 1.83, 95%CI = 1.21–2.77, and OR = 4.43, 95%CI = 2.22–8.83, respectively). Compliance was lower in the evening than in the morning (OR = 0.82, 95%CI = 0.69–0.97), indicating non-random patterns that could impact study validity.

Conclusions

The findings of this study shed light on the complexities surrounding compliance with mobile EMA protocols among older adults in health behavior studies. Our analysis revealed that non-compliance within our pooled dataset was not completely random. This non-randomness could introduce bias into study findings, potentially compromising the validity of research findings. To address these challenges, we recommend adopting tailored approaches that take into account individual characteristics and temporal dynamics. Additionally, the utilization of Directed Acyclic Graphs, and advanced statistical techniques can help mitigate the impact of non-compliance on study validity.
Genetic association of antinuclear antibodies with HLA in JIA patients: a Swedish cohort study
Authors: Saleh Raya , Sundberg Erik , Olsson Mia , Tengvall Katarina , Alfredsson Lars , Kockum Ingrid , Padyukov Leonid , Harris Helena Erlandsson
Published: August 2024

Background

Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition.

Methods

We analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm.

Results

Case–control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to HLA-DQA1 and HLA-DRB1. HLA-DRB1*08:01, HLA-DQA1*04:01, and HLA-DQB1*04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the HLA-DRB1-DQA1-DQB1 haplotype, our analysis suggests that HLA-DRB1*08 might be the primary allele linked to JIA susceptibility. The HLA-DRB1*11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the HLA-DRB1-DQA1-DQB1 haplotype, HLA-DRB1*11, and HLA-DPB1*02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity.

Conclusions

This study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.
Contextualizing family planning messages for the BornFyne-PNMS digital platform in Cameroon: a community-based approach
Authors: Nkangu Miriam , Detchaptche Sarah Pascale Ngassa , Njoache Mildred , Fantaye Arone , Wanda Franck , Ngo Valery , Obegu Pamela , Kasonde Mwenya , Buh Amos , Sinsai Regina , Kepgang Evrard , Kibu Odette , Tassegning Armel , Fobellah Nkengfac , Elate Nfongue , Tabebot Alice , Weledji Donald , Little Julian , Yaya Sanni
Published: August 2024

Background

Family planning (FP) is crucial for reducing maternal and infant mortality and morbidity, particularly through the prevention of unsafe abortions resulting from unwanted pregnancies. Despite Cameroon’s commitment to increasing the adoption of modern FP strategies, rural and poor populations still exhibit low demand due to limited access to healthcare services. This study documents the approach in developing family planning messages for the BornFyne prenatal management system as a platform to improve family planning awareness and enhance uptake.

Method

This is a mixed-methods study that employed the Health Belief Model (HBM). The study included a cross-sectional survey and focus group discussions in four districts of Cameroon. The survey explored household perspectives of FP and the use of mobile phone. Focus group discussions involved women, men, and community health workers to gain in-depth insights. Thematic analysis using themes from the HBM guided the analysis, focusing on perceived benefits, barriers, and cues to action.

Results

The survey included 3,288 responses. Thematic analysis of focus group discussions highlighted knowledge gaps and areas requiring additional information. Identified gaps informed the development of targeted FP messages aligned with BornFyne objectives and the Health Belief Model. Results revealed that most respondents recognized the benefits of FP but faced knowledge barriers related to side effects, cultural influences, and communication challenges between partners. Focus group discussions further highlighted the need for education targeting both men and women, dispelling misconceptions, and addressing adolescent and youths’ ignorance. The study emphasized the importance of tailored messaging for specific demographic groups and culture.

Conclusion

Developing effective FP intervention messages requires a nuanced understanding of community perspectives. The BornFyne-PNMS family planning feature, informed by the Health Belief Model, addresses knowledge gaps by delivering educational messages in local dialects via mobile phones. The study’s findings underscore the importance of community-based approaches to contextualizing and developing FP content targeting specific populations to generate tailored messages to promote awareness, acceptance, and informed decision-making. The contextualized and validated messages are uploaded into the BornFyne-family planning feature.
Multi-omics association study of DNA methylation and gene expression levels and diagnoses of cardiovascular diseases in Danish Twins
Authors: Skovgaard Asmus Cosmos , Mohammadnejad Afsaneh , Beck Hans Christian , Tan Qihua , Soerensen Mette
Published: August 2024

Background

Cardiovascular diseases (CVDs) are major causes of mortality and morbidity worldwide; yet the understanding of their molecular basis is incomplete. Multi-omics studies have significant potential to uncover these mechanisms, but such studies are challenged by genetic and environmental confounding—a problem that can be effectively reduced by investigating intrapair differences in twins. Here, we linked data on all diagnoses of the circulatory system from the nationwide Danish Patient Registry (spanning 1977–2022) to a study population of 835 twins holding genome-wide DNA methylation and gene expression data. CVD diagnoses were divided into prevalent or incident cases (i.e., occurring before or after blood sample collection (2007–2011)). The diagnoses were classified into four groups: cerebrovascular diseases, coronary artery disease (CAD), arterial and other cardiovascular diseases (AOCDs), and diseases of the veins and lymphatic system. Statistical analyses were performed by linear (prevalent cases) or cox (incident cases) regression analyses at both the individual-level and twin pair-level. Significant genes (p < 0.05) in both types of biological data and at both levels were inspected by bioinformatic analyses, including gene set enrichment analysis and interaction network analysis.

Results

In general, more genes were found for prevalent than for incident cases, and bioinformatic analyses primarily found pathways of the immune system, signal transduction and diseases for prevalent cases, and pathways of cell–cell communication, metabolisms of proteins and RNA, gene expression, and chromatin organization groups for incident cases. This potentially reflects biology related to response to CVD (prevalent cases) and mechanisms related to regulation and development of disease (incident cases). Of specific genes, Myosin 1E was found to be central for CAD, and DEAD-Box Helicase 5 for AOCD. These genes were observed in both the prevalent and the incident analyses, potentially reflecting that their DNA methylation and gene transcription levels change both because of disease (prevalent cases) and prior disease (incident cases).

Conclusion

We present novel biomarkers for CVD by performing multi-omics analysis in twins, hereby lowering the confounding due to shared genetics and early life environment—a study design that is surprisingly rare in the field of CVD, and where additional studies are highly needed.
CT-based multimodal deep learning for non-invasive overall survival prediction in advanced hepatocellular carcinoma patients treated with immunotherapy
Authors: Xia Yujia , Zhou Jie , Xun Xiaolei , Zhang Jin , Wei Ting , Gao Ruitian , Reddy Bobby , Liu Chao , Kim Geoffrey , Yu Zhangsheng
Published: August 2024

Objectives

To develop a deep learning model combining CT scans and clinical information to predict overall survival in advanced hepatocellular carcinoma (HCC).

Methods

This retrospective study included immunotherapy-treated advanced HCC patients from 52 multi-national in-house centers between 2018 and 2022. A multi-modal prognostic model using baseline and the first follow-up CT images and 7 clinical variables was proposed. A convolutional-recurrent neural network (CRNN) was developed to extract spatial-temporal information from automatically selected representative 2D CT slices to provide a radiological score, then fused with a Cox-based clinical score to provide the survival risk. The model’s effectiveness was assessed using a time-dependent area under the receiver operating curve (AUC), and risk group stratification using the log-rank test. Prognostic performances of multi-modal inputs were compared to models of missing modality, and the size-based RECIST criteria.

Results

Two-hundred seven patients (mean age, 61 years ± 12 [SD], 180 men) were included. The multi-modal CRNN model reached the AUC of 0.777 and 0.704 of 1-year overall survival predictions in the validation and test sets. The model achieved significant risk stratification in validation (hazard ratio [HR] = 3.330, p = 0.008), and test sets (HR = 2.024, p = 0.047) based on the median risk score of the training set. Models with missing modalities (the single-modal imaging-based model and the model incorporating only baseline scans) can still achieve favorable risk stratification performance (all p < 0.05, except for one, p = 0.053). Moreover, results proved the superiority of the deep learning-based model to the RECIST criteria.

Conclusion

Deep learning analysis of CT scans and clinical data can offer significant prognostic insights for patients with advanced HCC.

Critical relevance statement

The established model can help monitor patients’ disease statuses and identify those with poor prognosis at the time of first follow-up, helping clinicians make informed treatment decisions, as well as early and timely interventions.

Key Points

An AI-based prognostic model was developed for advanced HCC using multi-national patients.

The model extracts spatial-temporal information from CT scans and integrates it with clinical variables to prognosticate.

The model demonstrated superior prognostic ability compared to the conventional size-based RECIST method.

Graphical Abstract
A radioligand for in vitro autoradiography of CSF1R in post-mortem CNS tissues
Authors: Foss Catherine A. , Naik Ravi , Das Deepankar , Cha Hyojin , Minn Il , Hall Andrew , Finley Paige , Wu Sophia Jiang , Du Yong , Dannals Robert F. , Pomper Martin G. , Horti Andrew G.
Published: August 2024

Background

Reactive microglia and recruited peripheral macrophages contribute to the pathogenesis of Alzheimer’s dementia (AD). Monocytes, macrophages and microglia all express the marker colony-stimulating factor 1 receptor (CSF1R). 4-Cyano-N-(4-(4-methylpiperazin-1-yl)-2-(4-methylpiperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide (1) is a high-affinity antagonist for CSF1R. We report the radiosynthesis of both [3H]1 and [11C]1. The PET imaging properties of [11C]1 in mice and baboon were investigated. [3H]1 was studied in Bmax measurement in post-mortem autoradiography in the frontal cortex, inferior parietal cortex and hippocampus from donors diagnosed with AD and age-matched controls. In vitro binding affinity of 1 was measured commercially. Nor-methyl-1 precursor was radiolabeled with [11C]iodomethane or [3H]iodomethane to produce [11C]1 and [3H]1, respectively. Ex vivo brain biodistribution of [11C]1 was compared in normal mice versus lipopolysaccharide-administered (LPS) murine model of neuroinflammation. Dynamic PET imaging was performed in a healthy male Papio anubis baboon. Post-mortem autoradiography with [3H]1 was performed in frozen sections using a standard saturation binding technique.

Results

Compound 1 exhibits a high in vitro CSF1R binding affinity (0.59 nM). [11C]1 was synthesized with high yield. [3H]1 was synthesized similarly (commercially). Biodistribution of [11C]1 in healthy mice demonstrated moderate brain uptake. In LPS-treated mice the brain uptake of [11C]1 was ~ 50% specific for CSF1R. PET/CT [11C]1 study in baboon revealed low brain uptake (0.36 SUV) of [11C]1. Autoradiography with [3H]1 gave significantly elevated Bmax values in AD frontal cortex versus control (47.78 ± 26.80 fmol/mg vs. 12.80 ± 5.30 fmol/mg, respectively, P = 0.023) and elevated, but not significantly different binding in AD hippocampus grey matter and inferior parietal cortex (IPC) white matter.

Conclusions

Compound 1 exhibits a high in vitro CSF1R binding affinity. [11C]1 specifically labels CSF1R in the mouse neuroinflammation, but lacks the ability to efficiently cross the blood–brain barrier in baboon PET. [3H]1 specifically labels CSF1R in post-mortem human brain. The binding of [3H]1 is significantly higher in the post-mortem frontal cortex of AD versus control subjects.
Integrating surgical intervention and watch-and-wait approach in dMMR metastatic rectal cancer with pembrolizumab: a case report
Authors: Ando Yohei , Sakurai Tsubasa , Ozaki Kosuke , Matsui Shimpei , Mukai Toshiki , Yamaguchi Tomohiro , Akiyoshi Takashi , Nakayama Izuma , Shigematsu Yasuyuki , Oba Atsushi , Chino Akiko , Fukunaga Yosuke
Published: August 2024

Background

Treating rectal cancer presents challenges due to postoperative complications and reduced quality of life (QOL). Recent evidence supports the watch-and-wait (WW) approach for patients with a clinical complete response (cCR) following preoperative treatment. In this report, we discuss a case of metastatic rectal cancer with deficient mismatch repair (dMMR) treated successfully with pembrolizumab.

Case presentation

A 47-year-old male with dMMR rectal cancer and a single liver metastasis underwent treatment with pembrolizumab as neoadjuvant therapy. After 10 courses, the rectal lesion achieved cCR, prompting the selection of the WW approach. The liver metastasis showed significant shrinkage; however, the presence of a residual tumor was suspected, leading to a metastasectomy. A pathological complete response (pCR) was confirmed via histological examination. During a 24-month follow-up, there was no evidence of tumor regrowth, local recurrence, or distant metastasis.

Conclusions

The WW strategy is increasingly accepted for patients achieving cCR after preoperative treatment. While pCR in dMMR rectal cancer patients treated with immune checkpoint inhibitors (ICIs) has been documented, accurately predicting pCR from imaging remains challenging. This case illustrates that integrating ICI therapy, surgical interventions, and the WW approach can effectively achieve both oncological safety and improved QOL in the treatment of dMMR metastatic rectal cancer.
A case of abdominal aortic aneurysm presenting with multiple organs embolization
Authors: Tanaka Shinichi , Ohmine Takahiro , Maeda Takashi
Published: August 2024

Background

Distal embolization as the first manifestation of an abdominal aortic aneurysm (AAA) is relatively rare. AAAs presenting with multiple organs embolization are rarer and serious systemic conditions. There are no reports of life-saving outcomes in patients with AAAs presenting with multiple organs embolization prior to surgery.

Case presentation

A 78-year-old man presented with right acute lower limb ischemia (ALLI) and ischemic enteritis coexisting with an 83-mm AAA with a large mural thrombus. Although the patient underwent successful revascularization with endovascular treatment for right ALLI, the manifestation of ischemia of the calf muscles and infection forced right above-knee amputation. The patient also presented with ischemic colitis that resolved with conservative treatment. After receiving appropriate medical therapy and rehabilitation, the patient was successfully treated with open aortic repair for the AAA.

Conclusion

We successfully performed open aortic surgery for a rare case of AAA presenting with multiple organs embolization.
Clinical profiles and functional outcomes in elderly stroke survivors undergoing neurorehabilitation: a retrospective cohort study
Authors: Albu Sergiu , Izcara López de Murillas Elisenda , Secanell Espluga Mariona , Jimenez Crespo Andrea , Kumru Hatice
Published: August 2024

Background

This retrospective study characterizes clinical profiles and evolution of elderly stroke patients undergoing neurorehabilitation. Additionally, it identifies predictors of functional outcomes and hospital length of stay (LOS). For this purpose, patients aged ≥ 60 years admitted for neurorehabilitation within 6 months post-stroke, were recruited between January 2015 and August 2022. Rehabilitation profiles were identified using two-step clustering analysis, including the Modified Rankin Score (mRS), the National Institutes of Health Stroke Scale (NIHSS) and the motor and cognitive Functional Independence Measure (m-FIM and c-FIM) upon admission. FIM-effectiveness was calculated as (FIM-discharge−FIM-admission)/(maximum FIM−FIM-admission). Linear regression analyses were conducted to identify predictors of functional outcomes and LOS (days).

Results

The study enrolled 104 patients (68 male; mean age = 69.45 ± 6.5 years). Three clusters were identified: “Moderate” [NIHSS = 7.70 ± 3.21, motor-FIM = 59.42 ± 12.24, cognitive-FIM = 26.96 ± 4.69, mRS = 4 (4–4), aphasia = 41.7%, severe dysphagia = 4.2%, LOS = 45 (33.25–59) days]; “Moderate-severe” [NIHS = 10.40 ± 3.23, motor-FIM = 28.00 ± 7.74, cognitive-FIM = 25.92 ± 6.55, mRS = 4 (4–5), aphasia = 13%, severe dysphagia = 6.4%, LOS = 61 (45–92) days]; and “Severe” group [NIHS = 18.76 ± 4.19, motor-FIM = 16.12 ± 6.69, cognitive-FIM = 10.58 ± 4.14, mRS = 5 (5–5), aphasia = 60.6%, severe dysphagia = 42.4%, LOS = 71 (60.5–97.5) days]. The motor and cognitive FIM effectiveness significantly improved in the “Moderate” (m-FIM-effectiveness = 33.70 [12.16–53.54]; c-FIM-effectiveness = 33.3 [0–50.0]) and “Moderate-severe” cluster (m-FIM-effectiveness = 31.15 [10.34–46.55]; c-FIM-effectiveness = 33.3[0–63.16]) compared to the “Severe” cluster (m-FIM-effectiveness = 5.77 [0–18.77]; c-FIM-effectiveness = 4.65 [0–22.30]) (p = 0.001 and p = 0.025), whereas aphasia and dysphagia improved in all groups (p > 0.1). Severe stroke (NIHSS) (β = 0.33, p < 0.001), greater functional dependence (mRS) (β = 0.24, p = 0.013), presenting dysphagia (β = 0.30, p = 0.002), neuropathic pain (β = 0.22, p = 0.02), depression (β = 0.29, p = 0.003) or in-hospital infections (β = 0.23, p = 0.02) predicted higher LOS.

Conclusions

Patient clustering proves valuable in identifying distinct stroke rehabilitation profiles. Low FIM on admission, severe dysphagia, in-hospital infections, and psychotropic medication use, predicted poor functional outcomes and longer hospitalization.
Realignment of federal environmental policies to recognize fire’s role
Authors: Clark Sara A. , Archer Jenna N. , Stephens Scott L. , Collins Brandon M. , Hankins Don L.
Published: August 2024

Background

Enactment of the Clean Air Act (CAA), Endangered Species Act (ESA), and National Environmental Policy Act (NEPA), three of the primary federal environmental laws, all coincided with the height of fire suppression and exclusion in the United States. These laws fail to acknowledge or account for the importance of fire in many fire-adapted and fire-dependent ecosystems, particularly in the American west, or the imperative for fire restoration to improve resiliency and reduce wildfire risk as identified by western science and Indigenous knowledge. We review the statutory and regulatory provisions of these federal laws to identify how the existing policy framework misaligns with the unique role of fire in ecosystems and with Tribal sovereignty, identify specific barriers and disincentives to beneficial fire use, and propose specific policy reforms.

Results

The CAA, the ESA, and NEPA inhibit the use of beneficial fire as they are founded in a policy framework that treats fire restoration and maintenance as a federal action or human activity, rather than as a natural, baseline, or keystone process. The emergency exceptions in these policies reduce accountability and incentivize the wrong kind of fire, and compliance creates a perverse outcome by disincentivizing fire restoration. Further, these federal policies impede Tribal sovereignty.

Conclusions

Modifications to these laws would better enable fire restoration in fire-dependent and fire-adapted ecosystems, reduce wildfire risk, and ultimately meet the statutes’ core purposes. Federal agencies and Congress should reform regulatory frameworks to explicitly recognize fire as a baseline, natural, or keystone process, such that restoring fire in fire-dependent and fire-adapted ecosystems at levels not significantly exceeding pre-1800 fire return intervals is not treated as a federal or agency action. Further, non-Tribal governments should not attempt to regulate cultural burning, as it is a retained right of Indigenous peoples.
Broadening Access to STEM through the Community College: Investigating the Role of Course-Based Research Experiences (CREs)
Authors: Hanauer David I. , Graham Mark J. , Jacobs-Sera Deborah , Garlena Rebecca A. , Russell Daniel A. , Sivanathan Viknesh , Asai David J. , Hatfull Graham F.
Published: August 2024

In a propensity score -matching design students in course-based research experiences (CREs; here SEA-PHAGES) and traditional laboratory courses at the same community colleges were compared on a range of psychosocial variables. End-point outcomes revealed significantly higher ratings in the SEA-PHAGES for women and PEER students on important predictors of persistence.
Modeling a pure qP wave in attenuative transverse isotropic media using a complex-valued fractional viscoacoustic wave equation
Authors: Gu Bingluo , Zhang Shanshan , Huang Jianping , Xu Shibo , Han Jianguang
Published: August 2024

Seismic anisotropy, characterized by direction-dependent seismic velocity and attenuation, is a fundamental property of the earth, widely observed in field and laboratory measurements. This anisotropy significantly influences seismic wavefield attributes, such as amplitude, phase, and traveltime. Accurate quantification of anisotropy-related seismic wave propagation is essential for global- and regional-scale studies in seismology, such as imaging and inversion. Because the elastic assumption of the earth requires contending with S waves, which are often weak in our seismic recording, we derive a new general complex-valued spatial fractional Laplacian (SFL) viscoacoustic anisotropic pure quasi-P (qP) wave equation (WE) in attenuative transverse isotropic (A-TI) media under the acoustic assumption and use the fixed-order SFL operator to quantify seismic wave propagation in heterogeneous media. Our WE accurately captures anisotropic effects in seismic velocity and attenuation, even in strongly attenuative and anisotropic environments. It also describes the decoupled energy attenuation and velocity dispersion behaviors of the frequency-independent quality factor Q, beneficial for seismic imaging and inversion. Compared with existing viscoacoustic anisotropic pure qP WEs in A-TI media, our WE simplifies computational complexity and is easy to implement, as it decomposes into a complex-valued scalar operator and two differential operators. The evaluated dispersion curves further confirm the accuracy of our approach. Numerical examples in complex geologic settings demonstrate the new equation’s precision, stability, and efficiency in modeling seismic wave propagation.