bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiomultiomics: quantitative CT clusters of severe asthma associated with multiomics
Authors: Zounemat Kermani Nazanin , Chung Kian Fan , Macis Giuseppe , Santini Giuseppe , Clemeno Franz A.A. , Versi Ali , Sun Kai , Abdel-Aziz Mahmoud I. , Andersson Lars I. , Auffray Charles , Badi Yusef , Bakke Per , Brightling Chris , Brinkman Paul , Caruso Massimo , Chanez Pascal , De Meulder Bertrand , Djukanovic Ratko , Fabbri Leonardo , Fowler Stephen J. , Horvath Ildiko , Howarth Peter , James Anna J. , Kolmert Johan , Kraft Monica , Li Chuan-Xing , Maitland-van der Zee Anke H. , Malerba Mario , Papi Alberto , Rabe Klaus , Sanak Marek , Shaw Dominick E. , Singh Dave , Sparreman Mikus Maria , van Den Berge Maarten , Wheelock Asa M. , Wheelock Craig E. , Yasinska Valentyna , Guo Yi-ke , Wagers Scott , Barnes Peter J. , Bush Andrew , Sterk Peter J. , Dahlen Sven-Erik , Adcock Ian M. , Siddiqui Salman , Montuschi Paolo
Published: October 2024

Background

Lung quantitative computed tomography (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways, using radiomultiomics, integrating qCT, multiomics and machine learning/artificial intelligence.

Methods

We used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort. The same qCT measurements were used to replicate qCT clusters in a subsample of the ATLANTIS asthma cohort (n=97). We performed integrated enrichment analysis using blood, sputum, bronchial biopsies, bronchial brushings and nasal brushings transcriptomics and blood and sputum proteomics to characterise radiomultiomic-associated clusters (RACs).

Results

qCT clusters and clinical features in U-BIOPRED were replicated in the matched ATLANTIS cohort. In the U-BIOPRED cohort, RAC1 (n=30) was predominantly female with elevated body mass index, mild airflow limitation, decreased CT lung volume and increased lung density and upregulation of the complement pathway. RAC2 (n=34) subjects had airway wall thickness and a mild degree of airflow limitation, with upregulation of proliferative pathways including neurotrophic receptor tyrosine kinase 2/tyrosine kinase receptor B, and downregulation of semaphorin pathways. RAC3 (n=41) showed increased lung attenuation area and air trapping, severe airflow limitation, hyperinflation, and upregulation of cytokine signalling and signalling by interleukin pathways, and matrix metallopeptidase 1, 2 and 9.

Conclusions

U-BIOPRED severe asthma qCT clusters were replicated in a matched independent asthmatic cohort and associated with specific molecular pathways. Radiomultiomics might represent a novel strategy to identify new molecular pathways in asthma pathobiology.
Enormous headward and gully erosion in a floodplain area reclaimed for open-cast lignite mining during the July 2021 flood in the Inde River valley (Western Germany)
Authors: Keßels Johannes , Wolf Stefanie , Römer Wolfgang , Dörwald Lukas , Schulte Philipp , Lehmkuhl Frank
Published: October 2024

Background

The July flood 2021 at the mountain front of the Eifel-Ardennes Mountains and their foreland resulted in the flooding of the lignite mining area of Inden in Germany. The mining activities resulted in large-scale anthropogenic changes to the relief and fluvial system, leading to a landscape that is no longer adjusted to the recent process-response system. This paper concentrates on the Inde River, where lignite mining led to the relocation of a 5-km-long river section. The flood event resulted in the temporary avulsion of the Inde River into the former channel and, ultimately, in the flooding of the open-cast lignite mine Inden.

Results

The flooding of the open-cast lignite mine Inden led to headwall erosion and enormous sediment mobilisation, mobilising more than half a million cubic metres of sediment within a few hours, forming a 700-m-long deeply incised channel cut. Thereby, the underlying bedrock, near-subsurface man-made structures, and former river channels influence the erosional processes to different degrees. Surface erosion is likely to be the decisive process, and subsurface erosion is likely to play a secondary role. In both cases, former channels and mill ditches were likely impacting the course of erosional processes.

Conclusions

During high flood events open-cast mining sites in floodplains are endangered by enormous erosion and sediment transport within a short period of time (several hours). Understanding such complex erosion and depositional processes in open-cast mining areas could provide a blueprint for geomorphological processes and hazards in these anthropogenically shaped fluvial landscapes. Further, information on historic impact in the area is crucial to estimate potential risks.
Factors that affect the implementation of an integrated care programme for older people with different frailty levels: a qualitative study of commissioners and provider stakeholders
Authors: Khan Nimra , Hewson David , Randhawa Gurch
Published: October 2024

Introduction

The NHS has made it mandatory for General Practices in England to proactively identify and manage older people with moderate and severe frailty since the GMS contract of 2017/2018. In Luton, stakeholders developed the Luton Framework of Frailty (LFF) to implement this national policy. The aim of this study was to explore the factors that affect the implementation of this national policy at a local level.

Methods

In-depth interviews were conducted with 18 commissioners and service providers, all of whom were involved in providing services for older people with different frailty levels (OPDFL). Purposive and snowball sampling methods were used, with thematic analysis used for data analysis.

Results

Two main themes with several sub-themes were found. The first theme was the tension within existing national policy initiatives to provide integrated care services for OPDFL, which illuminated their strengths and limitations. Participants felt that new initiatives, such as the development of Primary Care Networks and Enhanced Health in Care Homes, have improved primary care coordination. However, the traditional reactive approach for managing older people who are frail was thought to be counterproductive, when an approach that focused on prevention and early intervention would have been better. The second theme concerned the contextual factors that affect implementation of integrated care. These included having key leaders at a local level, the requirement for more funding, as well as the need for good working relationships among service providers. However, the lack of awareness about the care pathways among GPs was thought to be a reason for the variation in the implementation of the LFF. The COVID-19 pandemic was perceived as a challenge for the implementation of the LFF. Finally, polices were thought to succeed only if more resources are provided, while the term frailty should be used with caution due to the negative connotations of OPDFL towards this term.

Conclusion

The implementation of an integrated care programme for OPDFL can be affected by several factors. Having proactive national policies that facilitate coordination and, having key leaders locally, the need for more funding, and good working relationships, are some of the contextual factors that could facilitate a successful implementation. In contrast, the lack of awareness of the care pathways that have been introduced locally, insufficient resources to deliver the programmes efficiently and a lack of careful consideration of how the term frailty is used could hinder this being put into practice.
A seroprevalence study indicates a high proportion of clinically undiagnosed MPXV infections in men who have sex with men in Berlin, Germany
Authors: Marcus Ulrich , Michel Janine , Lunchenkov Nikolay , Beslic Denis , Treindl Fridolin , Surtees Rebecca , Weber Christoph , Baumgarten Axel , Nitsche Andreas , Stern Daniel
Published: October 2024

Introduction

During the mpox outbreak in 2022, the highest number of cases in Germany were registered in Berlin, almost all of them in men who have sex with men (MSM). However, the frequency of clinically undiagnosed infections is unknown.

Methods

A cross-sectional study was conducted among MSM in Berlin, Germany. Participants were recruited from private practices and community-based checkpoints specialised in HIV and STI care for MSM. They were asked to complete an online questionnaire on socio-demographic data, mpox diagnosis, vaccination history and sexual behaviour, and to provide a blood sample for serological analysis. The samples were tested for antibodies against a range of antigens to distinguish between antibodies induced by mpox infection and MVA vaccination, with pre-immune sera from childhood smallpox vaccination as a confounding factor. Associations of behavioural variables with reported and suspected mpox diagnosis as the outcome were tested using univariable and multivariable logistic regression models.

Results

Between the 11th April and 1st July 2023, 1,119 participants were recruited in eight private practices and two community-based checkpoints in Berlin. All participants provided a blood sample for serological testing. Information for the online questionnaire was provided by 728 participants; core data on age and mpox history for participants who did not provide questionnaire data were provided by the practices for an additional 218 participants. A previous diagnosis of mpox was reported for/by 70 participants (7.4%). Using a conservative and strict case definition, we serologically identified an additional 91 individuals with suspected undiagnosed mpox infection. Individuals with reported or suspected mpox infections reported more condomless anal sex partners in the past 3 months (OR = 5.93; 95% CI 2.10-18.35 for 5–10 partners; OR = 9.53; 95% CI 2.72–37.54 for > 10 partners) and were more likely to report sexual contact with partners diagnosed with mpox (OR = 2.87; 95% CI 1.39–5.84).

Conclusion

A substantial proportion of mpox infections were clinically undiagnosed. The number of condomless anal sex partners was strongly associated with both confirmed and suspected undiagnosed mpox infection. Therefore, mpox control measures based on clinical diagnosis of mpox are likely to have limited effectiveness in preventing mpox transmission in outbreak situations because many infections remain unrecognised and undiagnosed.
Chronic pain and use of painkillers, healthcare services and long-term impairment among Syrian refugees: a cross-sectional study
Authors: Standnes Mari Bakken , Haukenes Inger , Lunde Astrid , Diaz Esperanza
Published: October 2024

Background

The global increase in forcibly displaced populations highlights the importance of understanding their health needs. Chronic pain is prevalent among refugees, poses significant personal and public health challenges, and complicates their integration into new home countries. Understanding refugees' pain post-migration and how it is being managed is crucial for ensuring adequate and timely interventions and fostering health equity. This paper explores the associations between pain levels and the use of painkillers, healthcare services, and long-term impairment among Syrian refugees with chronic pain, one year after their resettlement in Norway.

Methods

This cross-sectional study is based on survey data collected from 353 quota refugees in 2018–19, one year after resettlement in Norway. The primary outcomes were the use of painkillers, the use of healthcare services, and long-term impairment, according to reported chronic pain levels. Associations between these outcomes and chronic pain levels were studied using Poisson regression, adjusted by sociodemographic variables and trauma experience.

Results

Of the 353 adults included, 52% were women, and the median age was 36 years. A total of 5% reported very mild/mild, 10% moderate, and 12% strong/very strong chronic pain over the last four weeks. Significant associations were found between all chronic pain levels and use of non-prescription painkillers (adjusted relative risks (aRR) (95% CI)); mild (3.1 (2.0–4.7)), moderate (1.8 (1.1–2.8)), strong (1.7 (1.1–2.6)), and prescription painkillers; mild (4.6 (2.2–9.5)), moderate (5.6 (3.2–10.0)), strong (6.7 (3.9–11.3)), compared to those without chronic pain. Use of emergency rooms, specialist care, and hospitalization were significantly associated with strong chronic pain, with aRR (95% CI) of 2.0 (1.2–3.5), 3.9 (2.1–7.0) and 2.4 (1.3–4.4), respectively. Long-term impairment was strongly associated with chronic pain across all pain levels; mild (8.6 (5.6–13.49)), moderate (6.7 (4.3–10.5)) and strong (6.6 (4.3–10.4)).

Conclusion

Despite their young age, more than a quarter of the Syrian refugees in our study reported chronic pain one year after resettlement in Norway. High levels of pain were related to the use of medication, healthcare services, and long-term impairment. Understanding the dynamics of pain among refugees is crucial to ensure adequate and timely management.
Obesity and survival in advanced non-small cell lung cancer patients treated with chemotherapy, immunotherapy, or chemoimmunotherapy: a multicenter cohort study
Authors: Nie Wei , Lu Jun , Qian Jie , Wang Shu-Yuan , Cheng Lei , Zheng Liang , Tao Guang-Yu , Zhang Xue-Yan , Chu Tian-Qing , Han Bao-Hui , Zhong Hua
Published: October 2024

Background

The association of body mass index (BMI) with survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy, immunotherapy, or chemoimmunotherapy is controversial. We aimed to investigate these associations, including associations in male and female patients specifically, in a multicenter cohort study.

Methods

We retrospectively analyzed data from seven cohorts comprising 7021 advanced non-small cell lung cancer patients who received chemotherapy (three cohorts), immunotherapy (two cohorts), and chemoimmunotherapy (two cohorts) from five data sources, including a de-identified nationwide (US-based) NSCLC clinico-genomic database and two randomized, double-blind, phase 3 clinical trials. BMI was categorized as underweight, normal weight, overweight, or obese. Underweight patients were excluded because of their small proportion. The primary endpoints were the associations between BMI and progression-free survival (PFS) and overall survival (OS) stratified by treatment type and sex, which were assessed using Kaplan–Meier methods and adjusted Cox modeling. Meta-analyses were performed to combine the adjusted hazard ratios.

Results

In the pooled analysis, obesity was significantly associated with improved OS in patients receiving chemotherapy (hazard ratios [HR] = 0.84, 95% confidence interval (CI) 0.76–0.93), but there was no association with PFS (HR = 0.91, 95% CI 0.82–1.02). The association of BMI with OS for patients receiving chemotherapy differed by sex, with an inverse association in men (HR = 0.74, 95% CI 0.64–0.84), but no association observed in women (HR = 0.96, 95% CI 0.81–1.13, Pinteraction = 0.018). No impact of BMI on OS or PFS was detected in patients receiving immunotherapy or chemoimmunotherapy. Obese patients had the lowest level of tumor mutational burden, similar level of programmed death-ligand 1 expression and ESTIMATE scores.

Conclusions

Obesity may be associated with an increased overall survival among male patients treated with chemotherapy, whereas not associated with the outcomes in patients treated with immunotherapy or chemoimmunotherapy.
School-based healthy eating interventions for adolescents aged 10–19 years: an umbrella review
Authors: Samad Nandeeta , Bearne Lindsay , Noor Farha Musharrat , Akter Fahmida , Parmar Divya
Published: October 2024

Background

The benefits of healthy eating are well known, yet adolescent diet is often poor. School based interventions offer a promising option to promote healthy eating, however, evidence is unclear.

Aim

This umbrella review synthesised the current evidence on school-based interventions for healthy eating in adolescents (10–19 years old).

Methods

Using Joanna Briggs Institute (JBI) umbrella review guidelines, a systematic search was conducted on 11 electronic databases (PubMed, CINHAL, EMBASE, Science Direct, PsycINFO, MEDLINE, Scopus, ERIC, Web of Science, Cochrane Register of Systemic Review and JBI Evidence Synthesis) to identify reviews published between January 2000 and December 2023. Methodological quality was assessed using JBI critical appraisal tool. A narrative synthesis was conducted informed by the World Health Organisation’s Health Promoting School (HPS) framework that categorises school-based interventions into three components i.e., health education, school environment changes, and family and community involvement.

Results

Seventeen reviews were identified (including 347 unique primary studies) that were published between 2008 and 2023. 87% of the reviews were based on interventions in high- income countries, limiting applicability to low- and middle-income countries. Fourteen reviews were rated as high, two as moderate, and one was rated as low methodological quality. Evidence from 71% of the reviews (n = 14 reviews, 13 = high methodological quality) found that multi-component interventions (i.e., interventions incorporating more than two components of the HPS framework) improved adolescents’ knowledge and behaviour concerning healthy eating. At the individual level, tech-driven healthy eating curricula effectively improved eating behaviours of adolescents. These individual-level interventions proved to be more effective and sustainable when supported by system-level changes, such as modifying school environments including increased availability of healthy foods and involving parents to promote healthy eating for adolescents. However, limited evidence from only three reviews suggests mixed feasibility for technology-based interventions and lower feasibility for multi-component interventions. The lack of information on stakeholder involvement in intervention design is another critical evidence gap.

Conclusion

School-based multi-component healthy eating interventions that combine individual-level interventions with system-level changes are effective in promoting healthy eating behaviours among adolescents. Future reviews should assess the effectiveness of participatory approaches in intervention design, feasibility and scale-up studies, and analysing evidence from low- and middle-income countries.
Ex vivo nanoscale abluminal mapping of putative cargo receptors at the blood-brain barrier of expanded brain capillaries
Authors: Holst Mikkel Roland , Richner Mette , Arenshøj Pernille Olsgaard , Alam Parvez , Hyldig Kathrine , Nielsen Morten Schallburg
Published: October 2024

Receptor mediated transport of therapeutic antibodies through the blood-brain barrier (BBB) give promise for drug delivery to alleviate brain diseases. We developed a low-cost method to obtain nanoscale localization data of putative cargo receptors. We combine existing ex vivo isolation methods with expansion microscopy (ExM) to analyze receptor localizations in brain microcapillaries. Using this approach, we show how to analyze receptor localizations in endothelial cells of brain microcapillaries in relation to the abluminal marker collagen IV. By choosing the thinnest capillaries, microcapillaries for analysis, we ensure the validity of collagen IV as an abluminal marker. With this tool, we confirm transferrin receptors as well as sortilin to be both luminally and abluminally localized. Furthermore, we identify basigin to be an abluminal receptor. Our methodology can be adapted to analyze different types of isolated brain capillaries and we anticipate that this approach will be very useful for the research community to gain new insight into cargo receptor trafficking in the slim brain endothelial cells to elucidate novel paths for future drug design.
Redo aortic arch repair using trifurcated hybrid prosthesis after failed Ascyrus medical dissection stent treatment
Authors: Al-Obaidi Mustafa , Salem Razan , Walther Thomas , Holubec Tomas
Published: October 2024

Background

The management of acute type A aortic dissection (ATAAD) using the Ascyrus Medical Dissection Stent (AMDS) can lead to complications due to the persistence of the false lumen (FL). This case report presents two instances of failed AMDS treatment for ATAAD, highlighting the novel use of a trifurcated hybrid prosthesis for redo aortic arch repair using a minimally invasive frozen elephant trunk (FET) technique.

Case Presentation

Case 1: A 57-year-old male, previously treated with AMDS for ATAAD, presented with an enlarging aortic arch and persistent FL two years post-surgery caused by re-entry in the distal aortic arch. Redo surgery using the FET technique with an E-vita OPEN NEO Trifurcated hybrid prosthesis resulted in successful repair and partial FL thrombosis. Case 2: A 51-year-old male with prior AMDS treatment for ATAAD presented with severe aortic valve regurgitation and a maintained FL perfusion due to a residual re-entry in the proximal region of the descending aorta. Redo surgery using the FET technique with the same hybrid prosthesis led to successful repair and good recovery, confirmed by follow-up imaging.

Conclusions

The use of the E-vita OPEN NEO Trifurcated hybrid prosthesis in the FET technique offers a promising solution for redo aortic arch repair in cases of failed AMDS treatment for ATAAD. This approach can improve patient outcomes by addressing complications associated with persistent FL and enhancing long-term survival.
Understanding menstrual factors associated with poor mental health among female secondary school students in Uganda: a cross-sectional analysis
Authors: Ssesanga Titus , Thomas Katherine A. , Nelson Kate Andrews , Oenen Evaline , Kansiime Catherine , Lagony Stephen , Enomut Jonathan R. , Mayanja Yunia , Weiss Helen A.
Published: October 2024

Background

There is growing global concern about poor mental health among adolescents in sub-Saharan Africa. In particular, adolescent girls face multiple challenges in managing menstruation which can impact both their health and wellbeing. In this study we address an evidence gap on the association of a broad range of menstrual-related factors with mental health problems amongst secondary school female adolescents in Uganda.

Methods

We used baseline data from a cluster-randomised menstrual health intervention trial conducted in 60 secondary schools in two districts in Uganda. Baseline data were collected between March and July 2022, including socio-demographic characteristics, menstrual knowledge and attitudes, menstrual practices and self-efficacy, and mental health problems measured using the Strengths and Difficulties Questionnaire Total Difficulties score (SDQ-25). We used random-effects linear regression to estimate the adjusted mean difference (aMD) for the association between mental health problems (SDQ Total Difficulties Score) and menstrual-related factors, including the Menstrual Practice Needs Scale (MPNS) and the Self-Efficacy in Addressing Menstrual Needs scale (SAMNS)), accounting for school-level clustering and adjusting for prior confounders.

Results

Among the 3841 female participants, there was strong and consistent evidence of associations between mental health problems and menstrual-related factors. Mental health problems were associated with poor knowledge about menstruation (aMD = 1.17, 95%CI 0.50, 1.84 <0.001), using disposable and reusable menstrual products compared to using just disposable products (aMD = 1.42, 95%CI 0.92, 1.92, p <0.001), and experiencing menstrual pain even when using an effective management method at last menstrual period (LMP) compared to those experiencing no pain (aMD = 1.60, 95%CI 1.19, 2.01, p <0.001). Mental health problems were also associated with greater unmet menstrual needs according to the MPNS (aMD = 4.40 95%CI 3.96, 4.84, p <0.001), and with lower menstrual self-efficacy measured by the SAMNS (aMD = 0.94 95% CI 0.51, 1.37, p <0.001).

Conclusion

This study shows strong evidence that mental health problems reported by adolescent girls in Uganda are associated with poor menstrual health. The association between menstrual health and mental health provides evidence as to why menstrual health should be a public health priority.

Trial registration

Trial registration: ISRCTN 45461276. Registered on 16 September 2021.
When less is more: sketching with minimizers in genomics
Authors: Ndiaye Malick , Prieto-Baños Silvia , Fitzgerald Lucy M. , Yazdizadeh Kharrazi Ali , Oreshkov Sergey , Dessimoz Christophe , Sedlazeck Fritz J. , Glover Natasha , Majidian Sina
Published: October 2024

The exponential increase in sequencing data calls for conceptual and computational advances to extract useful biological insights. One such advance, minimizers, allows for reducing the quantity of data handled while maintaining some of its key properties. We provide a basic introduction to minimizers, cover recent methodological developments, and review the diverse applications of minimizers to analyze genomic data, including de novo genome assembly, metagenomics, read alignment, read correction, and pangenomes. We also touch on alternative data sketching techniques including universal hitting sets, syncmers, or strobemers. Minimizers and their alternatives have rapidly become indispensable tools for handling vast amounts of data.
Cognitive flexibility predicts attitudes towards vaccination: evidence from a New Zealand sample
Authors: Gomes-Ng Stephanie , Wood Jay K. , Cowie Sarah
Published: October 2024

Background

Vaccine hesitancy (the reluctance or refusal to vaccinate) poses a significant threat to public health worldwide, with declining vaccination coverage resulting in the resurgence of vaccine-preventable diseases (e.g., measles) in recent years. Despite efforts to combat vaccine hesitancy through information-based campaigns and other interventions, vaccine-hesitant attitudes persist. Given that such interventions likely expose individuals to information that conflicts with their own viewpoints about vaccination, cognitive flexibility – the ability to adapt one’s thoughts, attitudes, beliefs, or behavior in response to changing information or environmental demands – may play a role in vaccine hesitancy.

Methods

The current study investigated the relationship between cognitive flexibility and attitudes towards vaccination in a sample of New Zealand residents (N = 601). Cognitive flexibility was measured using perseverative responses in the Wisconsin Card-Sorting Task, and vaccination attitudes were measured using an adapted version of the Multidimensional Vaccine Hesitancy Scale (MVHS). Linear regression was used with MVHS scores as the dependent variable and cognitive flexibility and sociodemographic variables (age, gender, ethnicity, education level, religion) as predictors.

Results

Cognitive flexibility predicted personal barriers to vaccination (e.g.,” vaccines go against my personal beliefs”), with participants with lower levels of cognitive flexibility reporting greater personal barriers. In contrast, there was no significant relationship between cognitive flexibility and external barriers to vaccination (e.g., “vaccines cost too much”). Additionally, religious participants reported overall higher levels of vaccine hesitancy than non-religious participants.

Conclusions

These findings join others demonstrating that individual differences in cognitive style are associated with attitudes towards vaccination, and tentatively suggest that interventions aiming to reduce vaccine hesitancy may be more effective if combined with techniques to increase cognitive flexibility. To be sure, future work is needed to test the causal relationship between cognitive flexibility and attitudes towards vaccination.
Oxidative damage biomarkers and antioxidant enzymes in saliva of patients with peri-implant diseases
Authors: Özkan Karasu Yerda , Maden Oğuzhan , Çanakçı Cenk Fatih
Published: October 2024

Objectives

8-hydroxydeoxyguanosine (8-OHdG) and Malondialdehyde (MDA) are commonly used as markers to evaluate oxidative DNA and Lipid damage in disorders including chronic inflammatory diseases. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) protect tissues against oxidative injury from free oxygen radicals generated by various metabolic processes. The aim of this study was to evaluate 8-OHdG and MDA levels, and SOD and GPx activities in whole saliva of patients with peri-implant diseases.

Materials and methods

A cross-sectional study was conducted on a sum of 60 age gender balanced; peri-implantitis (n = 20), peri-mucositis (n = 20) and healthy (n = 20) individuals. Unstimulated whole saliva samples were collected and to determine the clinical condition of each subject; the plaque index (PI), gingival index (GI), peri-implant probing pocket depth (PIPD), peri-implant presence of bleeding on probing (BOP) (with/without suppuration) and radiographic signs of crestal bone loss (BL) were measured. The salivary 8-OHdG level was measured using the ELISA method. SOD, GPx activities and MDA levels were determined spectrophotometrically.

Results

A total of 60 individuals had evaluations of 318 implants. In comparison to the peri-mucositis and peri-implantitis groups, the healthy group had significantly lower PI and GI scores (p < 0.001). The PIPD value differed amongst the groups, with the peri-implantitis group having the highest value (p < 0.001). Compared to the peri-mucositis and control groups, the peri-implantitis group had a significantly higher BL score (p < 0.001 and p < 0.001, respectively). The peri-implantitis group showed a significantly higher 8-OHdG level (p < 0.001; p < 0.001 respectively) than the peri-mucositis and control groups. Compared to the peri-mucositis and control groups, the peri-implantitis group had a significantly higher MDA level (p < 0.001 and p < 0.001, respectively). The peri-implantitis group had a significantly higher SOD level (p < 0.001 and p < 0.001, respectively) in comparison to the peri-mucositis and control groups. There was no significant difference in GPx levels between the peri-mucositis and control groups (p > 0.05), while the peri-implantitis group had significantly lower GPx levels than the peri-mucositis and control groups (p < 0.001 and p < 0.001, respectively).

Conclusions

Elevated levels of oxidative stress in saliva may indicate the onset of pathological bone loss surrounding the implant and may be an indication of peri-implantitis.

Clinical relevance

In peri-implant diseases, changes may occur in the levels of 8-OHdG, MDA, SOD and GPx in saliva, which may lead to a deterioration in the oxidant/antioxidant balance.
Diagnosis and treatment of heart failure with preserved ejection fraction in patients on hemodialysis
Authors: Nitta Kosaku , Kinugawa Koichiro
Published: October 2024

Heart failure (HF) is a frequent complication and the main cause of death in patients on dialysis. HF with preserved ejection fraction (HFpEF) is a complicated syndrome that manifests as diastolic dysfunction and increased left ventricular filling pressure. Few studies have investigated HFpEF in dialysis patients, so the diagnosis and treatment of HFpEF remains challenging. The recently published the Japanese Circulation Society (JCS)/the Japanese Heart Failure Society (JHFS) 2021 guidelines have reported a new diagnostic procedure for HF. In dialysis patients, HF is typically observed as left ventricular diastolic dysfunction in association with HFpEF. Recent reports have shown that risk factors for HF in dialysis patients include not only traditional risk factors, such as age, smoking, obesity, hypertension, dyslipidemia, and diabetes, but also nontraditional risk factors such as fluid overload, renal anemia, disorders of calcium and phosphate metabolism, uremic toxins, and malnutrition. In the management of dialysis patients, volume control is important for controlling intradialytic hypotension, which is associated with higher mortality. Also, adequate pharmacological treatment of HFpEF is difficult in these patients, so a robust protocol developed for non-dialysis patients with HFpEF may be useful for treating patients on dialysis. This review explores the characteristics of hemodialysis patients with HFpEF and diagnostic and treatment procedures for these patients.
Pharmacokinetic interaction between single and multiple doses of darunavir, in combination with cobicistat or ritonavir, and single-dose dabigatran etexilate in healthy adults
Authors: Van Hemelryck Sandy , Van Landuyt Erika , Ariyawansa Jay , Palmer Martyn , Kothe Martine J. C. , Pollefliet Caroline
Published: October 2024

Objective

Darunavir (DRV) is a P-glycoprotein (P-gp) inhibitor. Dabigatran etexilate, prodrug of the anticoagulant dabigatran, is a P-gp probe substrate. This study evaluated the effect of single and multiple doses of DRV, coadministered with cobicistat (COBI) or ritonavir (rtv), on the pharmacokinetics (PK) of single-dose dabigatran etexilate.

Methods

This was an open-label, fixed-sequence, single-center, 2-panel, phase 1 study in which healthy adult participants were equally divided over 2 panels. In panel 1, participants received single and multiple doses of DRV/COBI 800/150 mg coadministered with single-dose dabigatran etexilate 150 mg. In panel 2, participants received single and multiple doses of DRV 800 mg + rtv 100 mg coadministered with single-dose dabigatran etexilate 150 mg. Key PK parameters evaluated were maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinity (AUCinf) for free and total dabigatran.

Results

Overall, 28 participants were enrolled and treated (n = 14 per panel). Dabigatran Cmax and AUCinf increased 2.64-fold after a single dose of DRV/COBI and 1.99- and 1.88-fold, respectively, after multiple doses of DRV/COBI. Dabigatran Cmax and AUCinf increased 1.64- and 1.72-fold, respectively, after a single dose of DRV + rtv and 1.22- and 1.18-fold, respectively, after multiple doses of DRV + rtv. In both panels, the most commonly reported adverse events were diarrhea and headache.

Conclusion

Findings of increased dabigatran exposure with DRV/COBI or DRV + rtv coadministration indicate an inhibitory effect of single-dose boosted DRV on P-gp, and a mixed inhibitory/inductive effect of multiple doses of boosted DRV on P-gp.

Trial registration

ClinicalTrials.gov, NCT04208061. Registered December 19, 2019
CT-based body composition analysis and pulmonary fat attenuation volume as biomarkers to predict overall survival in patients with non-specific interstitial pneumonia
Authors: Salhöfer Luca , Bonella Francesco , Meetschen Mathias , Umutlu Lale , Forsting Michael , Schaarschmidt Benedikt M. , Opitz Marcel , Beck Nikolas , Zensen Sebastian , Hosch René , Parmar Vicky , Nensa Felix , Haubold Johannes
Published: October 2024

Background

Non-specific interstitial pneumonia (NSIP) is an interstitial lung disease that can result in end-stage fibrosis. We investigated the influence of body composition and pulmonary fat attenuation volume (CTpfav) on overall survival (OS) in NSIP patients.

Methods

In this retrospective single-center study, 71 NSIP patients with a median age of 65 years (interquartile range 21.5), 39 females (55%), who had a computed tomography from August 2009 to February 2018, were included, of whom 38 (54%) died during follow-up. Body composition analysis was performed using an open-source nnU-Net-based framework. Features were combined into: Sarcopenia (muscle/bone); Fat (total adipose tissue/bone); Myosteatosis (inter-/intra-muscular adipose tissue/total adipose tissue); Mediastinal (mediastinal adipose tissue/bone); and Pulmonary fat index (CTpfav/lung volume). Kaplan–Meier analysis with a log-rank test and multivariate Cox regression were used for survival analyses.

Results

Patients with a higher (> median) Sarcopenia and lower (< median) Mediastinal Fat index had a significantly better survival probability (2-year survival rate: 83% versus 71% for high versus low Sarcopenia index, p = 0.023; 83% versus 72% for low versus high Mediastinal fat index, p = 0.006). In univariate analysis, individuals with a higher Pulmonary fat index exhibited significantly worse survival probability (2-year survival rate: 61% versus 94% for high versus low, p = 0.003). Additionally, it was an independent risk predictor for death (hazard ratio 2.37, 95% confidence interval 1.03–5.48, p = 0.043).

Conclusion

Fully automated body composition analysis offers interesting perspectives in patients with NSIP. Pulmonary fat index was an independent predictor of OS.

Relevance statement

The Pulmonary fat index is an independent predictor of OS in patients with NSIP and demonstrates the potential of fully automated, deep-learning-driven body composition analysis as a biomarker for prognosis estimation.

Key Points

This is the first study assessing the potential of CT-based body composition analysis in patients with non-specific interstitial pneumonia (NSIP).

A single-center analysis of 71 patients with board-certified diagnosis of NSIP is presented

Indices related to muscle, mediastinal fat, and pulmonary fat attenuation volume were significantly associated with survival at univariate analysis.

CT pulmonary fat attenuation volume, normalized by lung volume, resulted as an independent predictor for death.

Graphical Abstract
Functional associations of the gut microbiome with dopamine, serotonin, and BDNF in schizophrenia: a pilot study
Authors: Ghorbani Mahin , Stephen Joseph Gerard Benedict , Mei Mei Tew , Ramly Siti Salwa , Muhamad Rasat Muhammad Arif , Croft Lawrence , Parimannan Sivachandran , Rajandas Heera , Lee Su Yin
Published: October 2024

Background

Schizophrenia is a complex neuropsychiatric disorder with various etiologic factors. Aberrant levels of neurotransmitters or growth factors such as dopamine, serotonin, and BDNF have been shown to cause cognitive impairment in schizophrenia. Recently, the gut microbiome has also been suggested as a factor in the development of the disorder. To explore this potential link, we conducted a pilot study to examine the relationship between the gut microbiome and plasma levels of neurotransmitters and growth factors in schizophrenia. Shotgun metagenome sequencing of total RNA from fecal samples were used to profile the gut microbiome of schizophrenia patients (SCZ) and healthy controls (HC). The MetaPhlAn2 and HUMaN2 pipelines were used for bioinformatic analyses. ELISA was used to measure the plasma levels of dopamine, serotonin, and BDNF. Spearman’s rank correlation coefficient was used for correlation analysis.

Results

We found that butyrate-producing bacteria were enriched in HC, whereas succinate-producing bacteria, namely Phascolarctobacterium succinatutens and Paraprevotella clara, were enriched in SCZ. The gut microbiota of SCZ was enriched in lipid biosynthesis pathways related to bile-resistant bacteria, whereas phospholipid pathways linked with butyrate-producing bacteria were enriched in HC. Alistipes indistinctus, Dorea longicatena, and Roseburia inulinivorans were negatively correlated with dopamine levels. Roseburia intestinalis and Parabacteroides goldsteini were negatively correlated with serotonin and BDNF levels, respectively. We found a significant correlation between dopamine and serotonin levels, and the super-pathway of purine deoxyribonucleoside degradation.

Conclusions

This study provides further support that gut microbiota could modulate neurotransmitter levels. The results suggest that gut microbiome-targeted therapies may help to rebalance neurotransmitter levels, offering new hope for the treatment of schizophrenia.
Comparative assessment of the scientific structure of biomass-based hydrogen from a cross-domain perspective
Authors: Okuda Kunihiko , Sasaki Hajime
Published: October 2024

Biomass-based hydrogen production is an innovative approach for realizing carbon-neutral energy solutions. Despite their promise, both structures differ in terms of the biomass energy domain, which is at the entry point of the technology, and the hydrogen energy domain, which is at the exit point of the technology. In this study, we conducted structural and predictive analyses via cross-domain bibliometric analysis to clarify the differences in the structures and perspectives of researchers across domains and to suggest ways to strengthen collaboration to promote innovation. Our study revealed that the hydrogen energy domain has a balanced impact on realizing a hydrogen society using biomass-based hydrogen production technology, while the biomass energy domain has a strong interest in the process of processing biomass. The results reveal that different communities have different ideas about research, resulting in a divide in the areas to be achieved. This comparative analysis reveals the importance of synergistic progress through interdisciplinary efforts. By filling these gaps, our findings can lead to the development of a roadmap for future research and policy development in renewable energy and highlight the importance of a unified approach to sustainable hydrogen production. The contribution of this study is to provide evidence for the importance of cross-disciplinary cooperation for R&D directors and policy makers.
Exploring compound suitability and employing DFT calculations, molecular docking, and dynamics simulation to investigate potent compounds from podophyllum medicinal plants for breast cancer therapy
Authors: Mande Srinivasarao , Repudi Lalitha , Goswami Sanchari , Nallasivan P. Kumar , Gandla Kumaraswamy
Published: October 2024

Background

Breast cancer, one of the most often diagnosed malignancies worldwide, continues to take countless women's lives. Its treatment usually involves targeting the human estrogen receptor alpha (ERα). Current research explores the potential of natural compounds to regulate ERα activity, providing a hopeful direction for breast cancer therapy. Our study utilized a comprehensive approach to identify promising natural compounds for breast cancer treatment, including quantum descriptors, molecular docking, molecular dynamics simulations, and ADMET/pharmacokinetics analysis.

Results

Six natural compounds derived from podophyllum medicinal plants, namely 4-demethylpodophyllotoxin (NP1), α-peltatin (NP2), podophyllotoxin (NP3), deoxypodophyllotoxin (NP4), podophyllotoxone (NP5), and β-peltatin (NP6), were investigated as potential selective estrogen receptor α (ERα) inhibiting agents for breast cancer. These compounds demonstrated the strongest binding affinity to the target enzyme, with binding energies of  − 8.9 and  − 8.1 kcal/mol, respectively. Further assessments of drug-likeness and ADME properties were conducted for these compounds, along with quantum calculations (HOMO–LUMO) to evaluate their reactivity. Additionally, molecular dynamics studies were performed to assess the stability of the NP1 and NP2 protein–ligand complexes.

Conclusions

We analyzed six natural compounds comprehensively, evaluating their ADME properties, molecular docking interactions, quantum descriptors, and dynamic simulations. Our findings demonstrate that these natural compounds are promising possibilities for treating breast cancer. Additionally, they may provide a basis for developing future compounds targeting estrogen receptor α (ERα) activity.

Graphical abstract
Identification and interaction analysis of molecular markers in myocardial infarction by bioinformatics and next-generation sequencing data analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya
Published: October 2024

Background

Cardiovascular diseases are prevalent worldwide with any age, and it is characterized by sudden blockage of blood flow to heart and permanent damage to the heart muscle, whose cause and underlying molecular mechanisms are not fully understood. This investigation aimed to explore and identify essential genes and signaling pathways that contribute to the progression of MI.

Methods

The aim of this investigation was to use bioinformatics and next-generation sequencing (NGS) data analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in MI. NGS dataset (GSE132143) was downloaded from the Gene Expression Omnibus (GEO) database. DEGs between MI and normal control samples were identified using the DESeq2 R bioconductor tool. The gene ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed using g:Profiler. Next, four kinds of algorithms in the protein–protein interaction (PPI) were performed to identify potential novel biomarkers. Next, miRNA-hub gene regulatory network analysis and TF-hub gene regulatory network were constructed by miRNet and NetworkAnalyst database, and Cytoscape software. Finally, the diagnostic effectiveness of hub genes was predicted by receiver operator characteristic curve (ROC) analysis and AUC more than 0.800 was considered as having the capability to diagnose MI with excellent specificity and sensitivity.

Results

A total of 958 DEGs were identified, consisting of 480 up-regulated genes and 478 down-regulated genes. The enriched GO terms and pathways of the DEGs include immune system, neuronal system, response to stimulus and multicellular organismal process. Ten hub genes (namely cftr, cdk1, rps13, rps15a, rps27, notch1, mrpl12, nos2, ccdc85b and atn1) were obtained via protein–protein interaction analysis results. MiRNA-hub gene regulatory network and TF-hub gene regulatory network showed that hsa-mir-409-3p, hsa-mir-3200-3p, creb1 and tp63 might play an important role in the MI.

Conclusions

Analysis of next-generation sequencing dataset combined with global network information and validation presents a successful approach to uncover the risk hub genes and prognostic markers of MI. Our investigation identified four risk- and prognostic-related gene signatures, including cftr, cdk1, rps13, rps15a, rps27, notch1, mrpl12, nos2, ccdc85b and atn1. This gene sets contribute a new perspective to improve the diagnostic, prognostic, and therapeutic outcomes of MI.
Utility of clinical, laboratory, and lymph node MYD88 L265P mutation in risk assessment of diffuse large B-cell lymphoma patients
Authors: Hanbal Ahmed Talaat , El-Ashwah Shaimaa , Eladl Ahmed E. , Shamaa Sameh , Saleh Layla M.
Published: October 2024

Background

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma and is characterized by heterogeneity in biology and clinical behavior. Mutations in the myeloid differentiation primary response 88 (MYD88) are found in different lymphoproliferative disorders and are associated with variable clinical and prognostic impact.

Aim

To investigate the frequency of MYD88 L265P mutation and its clinical impact in a cohort of Egyptian DLBCL patients.

Methods

FFPE lymph node samples from 87 DLBCL patients (46 males / 41 females; median age, 58 years) were included and analyzed for MYD88 L265P by an allele-specific PCR.

Results

MYD88 L265P mutations were found in 52 patients (59.8%) out of 87 DLBCL cases. Patients with L265 mutation were significantly younger than non-mutated patients (p = 0.022). None of the patients with the L265P mutation showed a significant association with the clinical parameters of DLBCL. Interestingly, MYD88 L265 mutated patients were found to be significantly correlated with HCV infection (p = 0.037). The median follow-up time across the entire cohort was 26 months. Univariate analysis showed that overall survival (OS) was affected by gender, LDH level, and CNS-IPI scoring (p = 0.048, 0.008, and 0.046, respectively), while disease-free survival (DFS) was affected by B symptoms and LDH level (p =  < 0.000 and 0.02, respectively). However, the MYD88 mutation status and other prognostic factors showed no association with OS or DFS.

Conclusions

Our findings indicate a high frequency of MYD88 L265P mutations in our study population and not associated with prognostic markers or the outcome of the disease.