bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting microgenderome: detecting and cataloguing sexually unique and enriched species in human microbiomes
Authors: Ma Zhanshan Sam
Published: December 2024

Background

Microgenderome or arguably more accurately microsexome refers to studies on sexual dimorphism of human microbiomes aimed at investigating bidirectional interactions between human microbiomes, sex hormones, and immune systems. It is important because of its implications to disease susceptibility and therapy, in which men and women demonstrate divergence in many diseases especially autoimmune diseases. In a previous report [1], we presented analyses of several key ecological aspects of microgenderome by leveraging the large datasets of the HMP (human microbiome project) but failed to offer species-level composition differences such as sexually unique species (US) and enriched species (ES). Existing approaches, for such tasks, including differential species relative abundance analysis and differential network analysis, possess certain limitations given that virtually all rely on species abundance alone or are univariate, while ignoring species distribution information across samples. Obviously, it is both species abundance and distribution that shape/drive the structure and dynamics of human microbiomes, and both should be equally responsible for the universal heterogeneity of microbiomes including the sexual dimorphism.

Results

Here, we fill the gap by taking advantages of a recently developed computational algorithm, species specificity, and specificity diversity (SSD) framework (refer to the companion article) to reanalyze the HMP and complementary seminovaginal microbiome datasets. The SSD framework can randomly search and catalogue the sexually specific unique/enriched species with statistical rigor, guided by species specificity (a synthetic metric of abundance and distribution) and specificity diversity (SD). The SSD framework reveals that men seem to have more unique species than women in their gut and reproductive system microbiomes, but women seem to have more unique species than men in the airway, oral, and skin microbiomes, which is likely due to sexual dimorphism in the hormone and immune systems. We further investigate co-dependency and heterogeneity of those sexually unique/enriched species across 15 body sites, with core/periphery network analyses.

Conclusions

This study not only produced sexually unique/enriched species in the human microbiomes and analyzed their codependency and heterogeneity but also further validated the robustness of the SSD framework presented in the companion article, by performing all negative control tests based on the HMP gut microbiome samples.
Pre-pregnancy LDL/HDL and total Cholesterol/HDL ratios are strong predictors of gestational diabetes mellitus in women undergoing assisted reproductive technologies
Authors: Liu Yvonne , Hocher Johann-Georg , Ma Shujuan , Hu Liang , Chen Huijun , Zhang Xiaoli , Gong Fei , Krämer Bernhard K. , Lin Ge , Hocher Berthold
Published: December 2024

Background & Objective

To analyze whether there is an association between pre-pregnancy lipid parameters and gestational diabetes mellitus (GDM) in women undergoing assisted reproductive technologies (ART), a group especially at risk for GDM, and if so, which parameter is associated the strongest.

Methods

Data was collected at the Reproductive and Genetic Hospital CITIC-Xiangya in Changsha, China from January 2017 to December 2018. The measured lipid parameters include LDL (low-density lipoprotein), HDL (high-density lipoprotein), TC (total cholesterol), and TG (triglycerides).

Results

119 (15.5%) of the 767 patients developed GDM. On average, women who developed GDM were older, had a higher BMI, LDL, TC, and TG, and lower HDL. After adjusting for confounders, LDL and HDL showed a significant association with GDM (p < 0.05), but TC and TG did not. Binary LDL/HDL and TC/HDL ratios showed the strongest association with GDM incidence (OR 1.957 [95%CI 1.258–3.044] and 1.942 [1.243–3.034] respectively). Subgroup analysis showed that an elevated LDL/HDL ratio also increased GDM risk in subgroups with a typically lower prevalence of GDM, such as young women with a low BMI and low blood pressure. Both lipid ratios (LDL/HDL and TC/HD) show strong interactions with baseline age, fasting plasma glucose, and LH.

Conclusions

In this cohort of Chinese women undergoing ART, pre-pregnancy LDL/HDL and TC/HDL were associated with GDM the strongest from the lipid parameters and could be useful to estimate GDM risk even before ART treatments and pregnancy.

Clinical trial number

NCT03503006 registered on the 21st of March 2018 (on clinicaltrials.gov). https://clinicaltrials.gov/study/NCT03503006?locStr=Changsha,%20Hunan,%20China&country=China&state=Hunan&city=Changsha&cond=ivf&rank=2.
Analysis of how a complex systems perspective is applied in studies on socioeconomic inequalities in health and health behaviour—a call for reporting guidelines
Authors: Mudd Andrea L. , Bal Michèlle , Verra Sanne E. , Poelman Maartje P. , Kamphuis Carlijn B. M.
Published: December 2024

Background

A complex systems perspective is gaining popularity in research on socioeconomic inequalities in health and health behaviour, though there may be a gap between its popularity and the way it is implemented. Building on our recent systematic scoping review, we aim to analyse the application of and reporting on complex systems methods in the literature on socioeconomic inequalities in health and health behaviour.

Methods

Selected methods and results from the review are presented as a basis for in-depth critical reflection. A traffic light-based instrument was used to assess the extent to which eight key concepts of a complex systems perspective (e.g. feedback loops) were applied. Study characteristics related to the applied value of the models were also extracted, including the model evidence base, the depiction of the model structure, and which characteristics of model relationships (e.g. polarity) were reported on.

Results

Studies that applied more key concepts of a complex systems perspective were also more likely to report the direction and polarity of relationships. The system paradigm, its deepest held beliefs, is seldom identified but may be key to recognize when designing interventions. A clear, complete depiction of the full model structure is also needed to convey the functioning of a complex system. We recommend that authors include these characteristics and level of detail in their reporting.

Conclusions

Above all, we call for the development of reporting guidelines to increase the transparency and applied value of complex systems models on socioeconomic inequalities in health, health behaviour and beyond.

Graphical Abstract
A fully human IgG1 antibody targeting connexin 32 extracellular domain blocks CMTX1 hemichannel dysfunction in an in vitro model
Authors: Tettey-Matey Abraham , Donati Viola , Cimmino Chiara , Di Pietro Chiara , Buratto Damiano , Panarelli Mariateresa , Reale Alberto , Calistri Arianna , Fornaini Maria Vittoria , Zhou Ruhong , Yang Guang , Zonta Francesco , Marazziti Daniela , Mammano Fabio
Published: December 2024

Connexins (Cxs) are fundamental in cell–cell communication, functioning as gap junction channels (GJCs) that facilitate solute exchange between adjacent cells and as hemichannels (HCs) that mediate solute exchange between the cytoplasm and the extracellular environment. Mutations in the GJB1 gene, which encodes Cx32, lead to X-linked Charcot-Marie-Tooth type 1 (CMTX1), a rare hereditary demyelinating disorder of the peripheral nervous system (PNS) without an effective cure or treatment. In Schwann cells, Cx32 HCs are thought to play a role in myelination by enhancing intracellular and intercellular Ca2+ signaling, which is crucial for proper PNS myelination. Single-point mutations (p.S85C, p.D178Y, p.F235C) generate pathological Cx32 HCs characterized by increased permeability (“leaky”) or excessive activity (“hyperactive”).

We investigated the effects of abEC1.1-hIgG1, a fully human immunoglobulin G1 (hIgG1) monoclonal antibody, on wild-type (WT) and mutant Cx32D178Y HCs. Using HeLa DH cells conditionally co-expressing Cx and a genetically encoded Ca2+ biosensor (GCaMP6s), we demonstrated that mutant HCs facilitated 58% greater Ca2+ uptake in response to elevated extracellular Ca2+ concentrations ([Ca2+]ex) compared to WT HCs. abEC1.1-hIgG1 dose-dependently inhibited Ca2+ uptake, achieving a 50% inhibitory concentration (EC50) of ~ 10 nM for WT HCs and ~ 80 nM for mutant HCs. Additionally, the antibody suppressed DAPI uptake and ATP release. An atomistic computational model revealed that serine 56 (S56) of the antibody interacts with aspartate 178 (D178) of WT Cx32 HCs, contributing to binding affinity. Despite the p.D178Y mutation weakening this interaction, the antibody maintained binding to the mutant HC epitope at sub-micromolar concentrations.

In conclusion, our study shows that abEC1.1-hIgG1 effectively inhibits both WT and mutant Cx32 HCs, highlighting its potential as a therapeutic approach for CMTX1. These findings expand the antibody’s applicability for treating diseases associated with Cx HCs and inform the rational design of next-generation antibodies with enhanced affinity and efficacy against mutant HCs.
Cross cultural adaptation and validation of the Hindi version of foot function index
Authors: Sidiq Mohammad , Chahal Aksh , Sharma Jyoti , Rai Richa Hirendra , Kashoo Faizan Zaffar , Jayavelu Jayaprakash , Kashyap Neha , Vajrala Krishna Reddy , Veeragoudhaman T. S. , Arasu Vinitha , Janakiraman Balamurugan
Published: December 2024

Background

The Foot Function Index (FFI) is a reliable and widely used standardized questionnaire that measures the impact of foot pathology on function. With 571 million Hindi-speaking people living globally and an increasing incidence of foot-related pathologies, it is imperative to cross-culturally translate and adapt a Hindi version of the FFI (FFI-Hi). We aimed to translate, cross-cultural adapt, and psychometrically test the FFI-Hi for use in Hindi-speaking individuals with foot conditions.

Methods

The translation of FFI-Hi was performed according to guidelines given by MAPI Research Trust. A total of 223 Hindi-speaking participants afflicted with foot conditions completed the FFI-Hi alongside the Short Form 36 (SF-36) questionnaire. The study duration spanned between October 2023 and January 2024. The initial phase was the translation and adaptation of FFI to cultural context. Followed by testing of psychometric properties involving of 133 participants for the test-retest reliability of FFI-Hi after a 7-day interval.

Results

The mean age of the participants was 47.10 (± 8.1) years. The majority of the participants were male (n = 148, 66.4%) and the most common foot condition was plantar fasciopathy (n = 91, 40.8%). The mean score of FF-Hi was 33.7 ± 11.7. The internal consistency of FFI-Hi was good with the Cronbach’s alpha (α) value of 0.891 and excellent reproducibility with the intra-class correlation of 0.90. The 95% minimal detectable change (MCD) and the standard error of measurement of the FFI-Hi was 22.02 and 7.94 respectively. Convergent validity between FFI-Hi subscales and SF-36 domains was moderate. Factor analysis corroborated the multidimensional nature of the FFI-Hi.

Conclusion

The FFI-Hindi version was successfully cross-culturally adapted, translated and demonstrated acceptable psychometric properties to be used in clinical practice and research. Further, the context-specific Hindi language version of FFI will enhance the utility of FFI in foot function evaluation and remove language barrier in patients reporting disability and activity limitation related to foot conditions.

Registration

Clinical Trials Registry of India (CTRI/2023/07/055734).
Firm, yet flexible: a fidelity debate paper with two case examples
Authors: Albers Bianca , Verweij Lotte , Blum Kathrin , Oesch Saskia , Schultes Marie-Therese , Clack Lauren , Naef Rahel
Published: December 2024

Background

In healthcare research and practice, intervention and implementation fidelity represent the steadfast adherence to core components of research-supported interventions and the strategies employed for their implementation. Evaluating fidelity involves determining whether these core components were delivered as intended. Without fidelity data, the results of complex interventions cannot be meaningfully interpreted. Increasingly, the necessity for firmness and strict adherence by implementers and their organizations has been questioned, with calls for flexibility to accommodate contextual conditions. This shift makes contemporary fidelity a balancing act, requiring researchers to navigate various tensions. This debate paper explores these tensions, drawing on experiences from developing fidelity assessments in two ongoing effectiveness-implementation hybrid trials.

Main body

First, given often scarce knowledge about the core components of complex interventions and implementation strategies, decisions about fidelity requirements involve a degree of subjective reasoning. Researchers should make these decisions transparent using theory or logic models. Second, because fidelity is context-dependent and applies to both interventions and implementation strategies, researchers must rethink fidelity concepts with every study while balancing firmness and flexibility. This is particularly crucial for hybrid studies, with their differing emphasis on intervention and implementation fidelity. Third, fidelity concepts typically focus on individual behaviors. However, since organizational and system factors also influence fidelity, there is a growing need to define fidelity criteria at these levels. Finally, as contemporary fidelity concepts prioritize flexible over firm adherence, building, evaluating, and maintaining fidelity in healthcare research has become more complex. This complexity calls for intensified efforts to expand the knowledge base for pragmatic and adaptive fidelity measurement in trial and routine healthcare settings.

Conclusion

Contemporary conceptualizations of fidelity place greater demands on how fidelity is examined, necessitating the expansion of fidelity frameworks to include organizational and system levels, the service- and study-specific conceptualizations of intervention and implementation fidelity, and the development of pragmatic approaches for assessing fidelity in research and practice. Continuing to build knowledge on how to balance requirements for firmness and flexibility remains a crucial task within the field of implementation science.
Immediate dam-sourced colostrum provision reduces calf mortality - management practices and calf mortality in large dairy herds
Authors: Keller Steffi , Donat Karsten , Söllner-Donat Stefanie , Wehrend Axel , Klassen Anne
Published: December 2024

Background

Farm-specific management practices greatly impact calf mortality rates. This cross-sectional study aimed to analyse the association between calf mortality and management practices in large dairy farms. A total of 93 dairy farms were voluntarily included in the study. All farms reared their own youngstock, and all but one kept more than 100 dairy cows. From March 2017 to March 2018, calf management practices were monitored during a farm visit, and farm managers were surveyed regarding calving procedures, neonate management, and environmental factors. Data were collated and analysed in conjunction with the 2017 calf mortality rate, as determined for each farm by using data from the German database of animal origin and movement (HI-Tier). All variables from the topics of colostrum supply, calf feeding, housing, health related information and calving preparation of the cows that resulted in P ≤ 0.1 in the analysis of variance were assumed to be associated with the calf mortality rate and were considered for a general linear mixed regression model.

Results

According to the data from the HI-Tier database of the 93 study herds from 2017, 54,474 calves were born alive and 3,790 calves died within the first six months of life. The calf mortality rate was lower on farms where calves were immediately provided with dam-sourced colostrum. Farm managers perceiving dust as the primary factor precipitating respiratory disease on the farm was positively associated with calf mortality. Regularly replacing bucket teats correlated with lower calf mortality rates compared to replacing them only upon detection of abrasion.

Conclusions

The study findings suggest that feeding calves with dam-sourced colostrum can potentially reduce overall calf mortality within the herd. This management practice holds comparable importance to ensuring successful passive transfer through timely and adequate colostrum feeding. Moreover, maintaining a low dust environment for the calves and consistently replacing bucket teats play significant roles in promoting better overall calf health.
Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysis
Authors: Chen Xiaokun , Jiang Guohua , Zhao Tianjing , Sun Nian , Liu Shanshan , Guo Hao , Zeng Canjun , Liu Yijun
Published: December 2024

Background

Diabetic polyneuropathy (DPN) is a common diabetes complication with limited treatment options. We aimed to identify circulating plasma proteins as potential therapeutic targets for DPN using Mendelian Randomization (MR).

Methods

The protein quantitative trait loci (pQTLs) utilized in this study were derived from seven previously published genome-wide association studies (GWASs) on plasma proteomics. The DPN data were obtained from the IEU OpenGWAS project. This study employed two-sample MR using MR-Egger and inverse-variance weighted methods to evaluate the causal relationship between plasma proteins and DPN risk, with Cochran’s Q test, and I2 statistics, among other methods, used to validate the robustness of the results.

Results

Using cis-pQTLs as genetic instruments, we identified 62 proteins associated with DPN, with 33 increasing the risk and 29 decreasing the risk of DPN. Using cis-pQTLs + trans-pQTLs, we identified 116 proteins associated with DPN, with 44 increasing the risk and 72 decreasing the risk of DPN. Steiger directionality tests indicated that the causal relationships between circulating plasma proteins and DPN were consistent with expected directions.

Conclusion

This study identified 96 circulating plasma proteins with genetically determined levels that affect the risk of DPN, providing new potential targets for DPN drug development, particularly ITM2B, CREG1, CD14, and PLXNA4.
Life cycle environmental impacts and costs of water electrolysis technologies for green hydrogen production in the future
Authors: Koj Jan Christian , Zapp Petra , Wieland Christoph , Görner Klaus , Kuckshinrichs Wilhelm
Published: December 2024

Background

To limit climate change and reduce further harmful environmental impacts, the reduction and substitution of fossil energy carriers will be the main challenges of the next few decades. During the United Nations Climate Change Conference (COP28), the participants agreed on the beginning of the end of the fossil fuel era. Hydrogen, when produced from renewable energy, can be a substitute for fossil fuel carriers and enable the storage of renewable energy, which could lead to a post-fossil energy age. This paper outlines the environmental impacts and levelized costs of hydrogen production during the life cycle of water electrolysis technologies.

Results

The environmental impacts and life cycle costs associated with hydrogen production will significantly decrease in the long term (until 2045). For the case of Germany, the worst-case climate change results for 2022 were 27.5 kg CO2eq./kg H2. Considering technological improvements, electrolysis operation with wind power and a clean heat source, a reduction to 1.33 kg CO2eq./kg H2 can be achieved by 2045 in the best case. The electricity demand of electrolysis technologies is the main contributor to environmental impacts and levelized costs in most of the considered cases.

Conclusions

A unique combination of possible technological, environmental, and economic developments in the production of green hydrogen up to the year 2045 was presented.

Based on a comprehensive literature review, several research gaps, such as a combined comparison of all three technologies by LCA and LCC, were identified, and research questions were posed and answered. Consequently, prospective research should not be limited to one type of water electrolysis but should be carried out with an openness to all three technologies. Furthermore, it has been shown that data from the literature for the LCA and LCC of water electrolysis technologies differ considerably in some cases. Therefore, extensive research into material inventories for plant construction and into the energy and mass balances of plant operation are needed for a corresponding analysis to be conducted. Even for today’s plants, the availability and transparency of the literature data remain low and must be expanded.
Lay people expect social modernization will bring more societal well-being: the relation between expected societal development, communion, agency and subjective well-being
Authors: Olechowski Mateusz , Krys Kuba
Published: December 2024

Background

Previous studies showed that lay people see modernization as a threat to social fabric because it will make people less warm and moral. The purpose of this paper is to describe lay people’s understanding of the effects of different types of modernization. Specifically, we checked how social, economic, technological and conventional development are expected to influence communion, agency and well-being in the future society.

Methods

We conducted three cross-sectional studies using online surveys. Prolific participant pool users over 18 years of age that held Canadian citizenship and resided in Canada were eligible to take part in the study in exchange for financial compensation. T-tests and linear regression analyses were conducted using SPSS statistical package.

Results

Participants expected that people in future society will have lower well-being than today. Technological modernization was expected to decrease communion and well-being but increase agency in the future, while social modernization was expected to strengthen societal communion, agency and well-being.

Conclusion

Lay people believe that different types of modernization will have different effects on society. Whereas technological progress is viewed ambivalently, social development is seen as uniformly positive for well-being of society. In order to counter pessimism about the future, policy makers should focus on social development while striving to mitigate negative social aspects of technological advancements.
The feasibility of a self-regulation and mental imagery programme to enhance everyday functioning for people with Parkinson’s disease: study protocol
Authors: Hill Christine , Pillay Renai , Liu Karen P. Y.
Published: December 2024

Background

Less dopaminergic neurons in people with Parkinson’s disease result in a reliance on a slow and energy-intensive control, restricting their ability to complete routine everyday activities. Self-regulation takes an active learning approach to rehabilitation by enhancing the person’s self-awareness and encourages self-reflection to overcome problems. Mental imagery assists the person to focus attention on the requirements for the task, making it a goal-directed action and allowing for faster movements. There is a growing body of evidence to support the use of self-regulation and mental imagery in rehabilitation to maintain or improve the performance of everyday activities for people with a neurological condition.

Methods

A prospective pilot study using a single-group, pre-test and posttest design will test the feasibility and acceptability of a self-regulation and mental imagery programme to enhance performance of everyday activities and motor and cognitive function in people with Parkinson’s disease. People who have a diagnosis of Parkinson’s disease with mild-to-moderate severity and intact attention, comprehension and short-term memory will be recruited. The participants will receive a 6-week programme with one therapist-led session, a home programme and a telephone call each week. The programme uses self-regulation through a step-based problem-solving process and mental imagery to assist in movement planning. Appropriate rehabilitation strategies are used as solutions to tackle problems experienced, impacting performance in everyday activities. The attendance rate will be recorded to indicate the feasibility. A questionnaire will be administered post-intervention to collect feedback on programme acceptability. Patient outcomes will include Barthel index, Lawton Instrumental Activities of Daily Living Scale, Canadian Occupational Performance Measure and Timed Up and Go test. Trail Making Test and Montreal Cognitive Assessment will be collected pre- and post-intervention.

Discussion

The programme aims to combine the metacognitive strategies of self-regulation and mental imagery to enable individuals with Parkinson’s disease to improve the performance of everyday activities. If feasible, the programme has the potential to be further tested in a randomised controlled trial and benefit people with Parkinson’s disease by enhancing their performance required in independent community living.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12621000903886, Registered on 12 July 2021 — retrospectively registered.
Thrombo-inflammation linking androgen suppression with cardiovascular risk in patients with prostate cancer
Authors: Beitzen-Heineke Antonia , Wise David R. , Berger Jeffrey S.
Published: December 2024

Androgen deprivation therapy (ADT), a key element of prostate cancer treatment, is associated with increased risk for cardiovascular morbidity and mortality. The underlying mechanisms include adverse metabolic alterations, but further mechanisms are likely. Animal studies suggest increased progression of atherosclerosis in androgen deprived conditions. Based on in vitro studies, lack of androgens may modulate immune cells including monocytes, macrophages, and T-cells towards a pro-inflammatory phenotype and pro-atherogenic function. As a novel aspect, this review summarizes existing data on the effect of androgens and androgen deprivation on platelet activity, which play a major role in inflammation and in the initiation and progression of atherosclerotic lesions. Testosterone modulates platelet aggregation responses which are affected by dose level, source of androgen, and age. Data on the effects of ADT on platelet activity and aggregation are limited and conflicting, as both increased and decreased aggregation responses during ADT have been reported. Gaps in knowledge about the mechanisms leading to increased cardiovascular risk during ADT remain and further research is warranted. Improved understanding of pathogenic pathways linking ADT to cardiovascular risk may help identify clinically useful diagnostic and prognostic biomarkers, and accelerate finding novel therapeutic targets, and thus optimize prostate cancer treatment outcomes.
Identifying innovation factors and actors in autonomous inland shipping: a literature review
Authors: Al Amien Dhaneswara
Published: December 2024

Autonomous shipping is introduced to increase the competitiveness of inland shipping and promote a modal shift toward sustainable transport. This innovation has the potential to disrupt the existing inland shipping industry paradigm. This paper identifies the characteristics of autonomous inland shipping through the lens of the diffusion of innovation theory. A systematic literature review, based on the PRISMA 2020 guidelines methodology, was conducted. The existing literature aligns well with the theory and reveals most of the innovation variables and relevant actors. The result indicates that the literature on this topic is limited but still developing, and the paper presents opportunities for agendas in business, innovation, and transportation research. Further discussion shows industry implications, using a generalized transport cost model and stakeholder analysis to emphasize the motivations for sustainable transport through the adoption of autonomous shipping.
Assessment of the physiological effects and safety of transpulmonary chemoembolization with doxorubicin on pulmonary tissue using a human-isolated lung perfusion model
Authors: Slama Alexis , Steinberg Hannah , Collaud Stéphane , Okumus Özlem , Hilger Ralph-Axel , Bauer Sebastian , Schildhaus Hans-Ulrich , Aigner Clemens , Schaarschmidt Benedikt M.
Published: December 2024

Background

Whole lung transpulmonary chemoembolization using a combination of doxorubicin (DXO) and degradable starch microspheres (DSM-TPCE) might be a promising treatment option in soft tissue sarcoma. To pave the way for clinical studies, this study aimed to evaluate the short-term effects of DSM-TPCE with DXO using an ex vivo isolated lung perfusion (ILP) model.

Methods

Nine lung specimens retrieved from patients undergoing lobectomy underwent ex vivo ILP. In groups of three, lung specimens were either treated with sole DXO, sole DSM, or combined substances (DSM + DXO). During ex vivo ILP, histological samples were obtained from each lung every 15 min. Quantitative DXO analysis and histopathological grading of possible tissue damage using a five-point Likert scale was performed. Two-way repeated measures ANOVA tested for differences between treatment groups and changes over time.

Results

We created a preclinical ex vivo ILP model to simulate the effects of DSM-TPCE. In histopathological analysis, only two specimens, treated with only DXO, showed an increase in parenchymal damage over time. No significant effect of time (3.3%, p = 0.305) or group (23.3; p = 0.331) was identified. Within the lung tissue, the DXO concentration ranged from 205 to 1,244 ng/g. No significant effects could be detected regarding different treatment groups (4.9% of total variation, p = 0.103).

Conclusion

In an ex vivo ILP model using human lung lobes, the physiological effects of DSM-TPCE with DXO could be tested. Neither increased DXO concentrations in lung tissue nor histopathological changes indicating early lung toxicity were observed.

Relevance statement

An ex vivo ILP model using human lung specimens did not show any signs of early lung toxicity after transpulmonary chemoembolization with DXO. These results support further evaluation of DSM-TPCE in phase I/II trials.

Key Points

Transpulmonary chemoembolization can be investigated in an ex vivo ILP model.

DSM did not increase DXO in normal lung tissue.

DSM did not increase parenchymal toxicity compared to the control groups.

Graphical Abstract
Focal liver lesions: multiparametric microvasculature characterization via super-resolution ultrasound imaging
Authors: Zeng Qian-Qian , An Shi-Zhe , Chen Chao-Nan , Wang Zhen , Liu Jia-Cheng , Wan Ming-Xi , Zong Yu-Jin , Jian Xiao-Hua , Yu Jie , Liang Ping
Published: December 2024

Background

Noninvasive and functional imaging of the focal liver lesion (FLL) vasculature at microscopic scales is clinically challenging. We investigated the feasibility of using super-resolution ultrasound (SR-US) imaging for visualizing and quantifying the microvasculature of intraparenchymal FLLs.

Methods

Patients with FLLs between June 2022 and February 2023 were prospectively screened. Following bolus injection of microbubbles at clinical concentration, SR-US was performed using a high frame rate (350–500 Hz) modified ultrasound scanner and a convex array transducer with a central frequency of 3.1 MHz.

Results

In total, 47 pathologically proven FLLs at a depth of 5.7 ± 1.7 cm (mean ± standard deviation) were included: 30 hepatocellular carcinomas (HCC), 11 liver metastases (LM), and 6 focal nodular hyperplasias (FNH). The smallest detectable vessel size of the hepatic microvasculature was 128.4 ± 18.6 μm (mean ± standard deviation) at a depth of 8 cm. Significant differences were observed among the three types of lesions in terms of pattern categories, vessel density, minimum flow velocity, and perfusion index. We observed higher vessel density for FNH versus liver parenchyma (p < 0.001) as well as fractal dimension and local flow direction entropy value for FNH versus HCC (p = 0.002 and p < 0.001, respectively) and for FNH versus LM (p = 0.006 and p = 0.002, respectively).

Conclusion

Multiparametric SR-US showed that these three pathological types of FLLs have specific microvascular phenotypes. Vessel density, fractal dimension and local flow direction entropy served as valuable parameters in distinguishing between benign and malignant FLLs.

Trial registration

ClinicalTrials.gov (NCT06018142).

Relevance statement

Multiparametric SR-US imaging offers precise morphological and functional assessment of the microvasculature of intraparenchymal focal liver lesions, providing insights into tumor heterogeneity and angiogenesis.

Key Points

Super-resolution (SR)-US imaging allowed morphological and functional evaluation of intraparenchymal hepatic lesion microvasculature.

Hepatocellular carcinoma, liver metastasis, and focal nodular hyperplasia exhibit distinct microvascular architectures and hemodynamic profiles.

Multiparametric microvasculature characterization via SR-US imaging facilitates the differentiation between benign and malignant microvascular phenotypes.

Graphical Abstract
Diagnostic value of digital breast tomosynthesis in suspicious lesions detected in screening mammogram
Authors: Mousa Waleed Abd El-Fattah , Tolba Dalia Ayman Abd El-Raof , Moawad Mahmoud Mohamed
Published: December 2024

Background

Digital mammography (DM) serves as the primary breast imaging technique for early cancer detection and diagnosis. However, it faces certain limitations, particularly in imaging dense breasts. DM exhibits reduced sensitivity and specificity in women with radiographically dense breast tissue due to diminished contrast between potential tumors and surrounding tissue, as well as tissue summation potentially obscuring lesions. The aim of this study was to assess the diagnostic efficacy of digital breast tomosynthesis compared to digital mammography in evaluating suspicious breast lesions. The study included 60 female patients eligible for mammography. All participants underwent full-field digital mammography and 3d tomosynthesis. Written informed consent was obtained from all subjects after explaining the research’s purpose and benefits. The Ethics Committee of the Faculty of Medicine, Menoufia University approved the study under code no. 10/2022RADI24.

Results

Regarding BIRADS classification: All 60 patients were categorized using the BIRADS lexicon for both mammography and digital breast tomosynthesis. Mammography results showed BIRADS 3 in 10% (6/60), BIRADS 4a in 33.3% (20/60), 4b in 10% (6/60), BIRADS 4c in 26.7% (16/60), and BIRADS 5 in 20% (12/60) of cases. In comparison, tomosynthesis classified cases as BIRADS 3 in 13.3% (8/60), 4b in 16.7% (10/60), BIRADS 4c in 23.3% (14/60), and BIRADS 5 in 46.7% (28/60) of cases.

Conclusions

Digital breast tomosynthesis (DBT) has established itself as a significant advancement in three-dimensional breast imaging for both screening and diagnostic purposes. It exhibits enhanced performance in identifying breast abnormalities and generates images of superior diagnostic quality with improved precision compared to conventional digital mammography. This improvement is particularly notable when examining dense breast tissue, which has traditionally been one of the most challenging aspects of breast imaging.
Mental health and its wider determinants in young people in the UK during 12 months of the COVID-19 pandemic: repeated cross-sectional representative survey
Authors: Rouquette Olivier Y. , Dekel Dana , Siddiqi Abdul-Moiz , Seymour Catherine , Weeks Lauren , John Ann
Published: December 2024

Background

The COVID-19 pandemic posed an unprecedented global challenge, with past evidence suggesting negative psychological effects with the additional concern that social and physical restrictions might disproportionately affect adolescents.

Aims

To explore mental health and its wider determinants in young people in the UK during 1 year of the COVID-19 pandemic (August 2020–August 2021).

Method

A representative sample of 11 898 participants (48.7% female) aged between 13 and 19 years (mean = 16.1) participated in five waves of data collection. Using validated self-reported questionnaires for loneliness, anxiety and depression, this survey measured the extent and nature of the mental health impacts of the coronavirus pandemic and help-seeking behaviours, and changes over time.

Results

Young people experienced higher levels of anxiety during the summer and fall 2020, followed by higher levels of depression during the winter 2020–2021, with loneliness gradually increasing then peaking during the spring and summer of 2021. Young people who were older, female, with pre-existing mental-health issues and experiencing financial difficulties were at higher risk of anxiety, depression and loneliness. Help-seeking behaviours reduced the risk of depression and loneliness.

Conclusions

The COVID-19 pandemic had substantial impact on young people, whether on their mental health, their social contacts and interactions or their perspective on what the future holds for them. Young people strongly advocated for better teacher training, and a better integration of mental health services, particularly within their schools.
Extremism, racism and riots: exploring the political, social and cultural determinants of poor mental health
Authors: Bhui Kamaldeep , Roberts Dianndra , Lashley Myrna , Jones Edgar , Kaufman Kenneth R.
Published: December 2024

The UK has seen an outbreak of riots after the death of three children in a knife attack. Misinformation about the suspect's heritage and religion was spread by social media, which was then used to incite violence and racism resulting in damage to property, terror and injuries. We put forward arguments that this was an extremist act and draw on the literature on terrorism, extremism and identity to put forward a deeper analysis of how this happened and what can be done to prevent future riots. We bring an interdisciplinary perspective drawing on research from social, cultural, psychological and political perspectives.
Development and Validation of Dynamic 5-Year Breast Cancer Risk Model Using Repeated Mammograms
Authors: Jiang Shu , Bennett Debbie L. , Rosner Bernard A. , Tamimi Rulla M. , Colditz Graham A.
Published: December 2024

PURPOSE

Current image-based long-term risk prediction models do not fully use previous screening mammogram images. Dynamic prediction models have not been investigated for use in routine care.

METHODS

We analyzed a prospective WashU clinic-based cohort of 10,099 cancer-free women at entry (between November 3, 2008 and February 2012). Follow-up through 2020 identified 478 pathology-confirmed breast cancers (BCs). The cohort included 27% Black women. An external validation cohort (Emory) included 18,360 women screened from 2013, followed through 2020. This included 42% Black women and 332 pathology-confirmed BC excluding those diagnosed within 6 months of screening. We trained a dynamic model using repeated screening mammograms at WashU to predict 5-year risk. This opportunistic screening service presented a range of mammogram images for each woman. We applied the model to the external validation data to evaluate discrimination performance (AUC) and calibrated to US SEER.

RESULTS

Using 3 years of previous mammogram images available at the current screening visit, we obtained a 5-year AUC of 0.80 (95% CI, 0.78 to 0.83) in the external validation. This represents a significant improvement over the current visit mammogram AUC 0.74 (95% CI, 0.71 to 0.77;
P
< .01) in the same women. When calibrated, a risk ratio of 21.1 was observed comparing high (>4%) to very low (<0.3%) 5-year risk. The dynamic model classified 16% of the cohort as high risk among whom 61% of all BCs were diagnosed. The dynamic model performed comparably in Black and White women.

CONCLUSION

Adding previous screening mammogram images improves 5-year BC risk prediction beyond static models. It can identify women at high risk who might benefit from supplemental screening or risk-reduction strategies.
Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial
Authors: Palmer Daniel H. , Jackson Richard , Springfeld Christoph , Ghaneh Paula , Rawcliffe Charlotte , Halloran Christopher M. , Faluyi Olusola , Cunningham David , Wadsley Jonathan , Darby Suzanne , Meyer Tim , Gillmore Roopinder , Lind Pehr , Glimelius Bengt , Falk Stephen , Ma Yuk Ting , Middleton Gary William , Cummins Sebastian , Ross Paul J. , Wasan Harpreet , McDonald Alec , Crosby Tom , Hammel Pascal , Borg David , Sothi Sharmila , Valle Juan W. , Mehrabi Arianeb , Bailey Peter , Tjaden Christine , Michalski Christoph , Hackert Thilo , Büchler Markus W. , Neoptolemos John P.
Published: December 2024

PURPOSE

The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria. Our aim was to analyze the ESPAC4 survival on long-term follow-up.

METHODS

The OS of 732 ESPAC4 patients comparing 367 randomly assigned to gemcitabine and 365 to GemCap was previously reported after a median follow-up time of 43.2 months (95% CI, 39.7 to 45.5) and 458 deaths. Analysis was now carried out after a median follow-up of 104 months (101-108) and 566 deaths.

RESULTS

The median OS was 29.5 months (27.5-32.1) for all patients, 28.4 months (25.2-32.0) in the gemcitabine group and 31.6 months (26.5-38.0) in the GemCap group (hazard ratio [HR], 0.83 [0.71 to 0.98];
P
= .031). R0 patients given gemcitabine had a median survival of 32.2 months (27.9-41.6) compared with 49.9 months (39.0-82.3) for those given GemCap (HR, 0.63 [0.47 to 0.84];
P
= .002). Lymph node-negative patients had significantly higher 5 year OS rates on GemCap (59% [49%-71%]) than gemcitabine (53% [42%-66%]; HR, 0.63 [0.41 to 0.98];
P
= .04) but not those with positive lymph nodes (
P
= .225). The OS advantage for GemCap was retained in the PRODIGE24 subgroup of 193 (26.4%) ESPAC4 patients not eligible for PRODIGE24 with a median survival of 20.7 (16.2-27.3) months in patients allocated to gemcitabine compared with 25.9 (22.3-30.2) months for ineligible patients allocated to GemCap (HR, 0.71 [95% CI, 0.52 to 0.98]; χ
2
log-rank-1df
= 4.31;
P
= .038).

CONCLUSION

GemCap is a standard option for patients not eligible for mFOLFIRINOX. Exploratory evidence suggests that GemCap may be particularly efficacious in R0 patients and also in lymph node-negative patients.
Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy
Authors: Bansal Rani , Adeyelu Tolulope , Elliott Andrew , Tan Antoinette R. , Ribeiro Jennifer R. , Meisel Jane , Oberley Matthew J. , Graff Stephanie L. , Sledge George W. , Grilley-Olson Juneko E. , Sammons Sarah L. , Rosenberger Laura H.
Published: December 2024

PURPOSE

Malignant phyllodes tumors (MPTs) are rare fibroepithelial tumors of the breast with aggressive biologic behavior and high recurrence rates. Surgery remains the primary treatment modality for these tumors; however, initial investigations suggest a potential for targeted therapies in managing this disease. Therefore, we aimed to assess the molecular landscape of MPTs to reveal possible treatment opportunities.

METHODS

MPTs (n = 57) from primary and metastatic sites underwent genomic sequencing (592-gene panel or whole exome), whole-transcriptome sequencing, and immunohistochemistry (PD-L1, human epidermal growth factor receptor 2 [HER2]) at Caris Life Sciences (Phoenix, AZ). Immune cell fractions in the tumor microenvironment were estimated using quanTIseq. Mann-Whitney
U
, chi-square, and Fisher’s exact tests were used to determine significance (
P
< .05).

RESULTS

MPTs had low
ERBB2
expression, comparable with the HER2-negative subset of a large cohort of breast adenocarcinoma samples (N = 9,926). Frequent alterations included
TERT
promoter;
MED12
,
TP53
, and
NF1
mutations; and less frequently
EGFR
,
PIK3CA
, and
BRAF
. Differences in mutation prevalences were observed between primary sites, lung metastases, and nonlung metastases. One MPT specimen harbored a pathogenic
TPM4:NTRK1
fusion, and treatment with larotrectinib for over 16 months suggested a clinical response to therapy. PD-L1+ status was observed in 15.2% of MPTs overall, with similar prevalence in primary sites and lung metastases. B cells, M2 macrophages, neutrophils, and natural killer cells had the highest median cell fractions in MPTs.

CONCLUSION

Considering the occurrence of several actionable alterations including a
TPM4:NTRK1
fusion reported herein, these results support the use of next-generation sequencing (NGS) including RNA analysis for fusion detection to identify such alterations in patients with MPTs. These findings highlight the importance of comprehensive NGS in MPT research to uncover potential targeted treatment options for these patients.
Macroscopic arrow of time from multiscale perspectives
Authors: Verma Mahendra K.
Published: December 2024

Fundamental laws of physics are symmetric under time reversal (T) symmetry, but the T symmetry is strongly broken in the macroscopic world. In this Perspective, I review T symmetry breaking frameworks: second law of thermodynamics, multiscale energy transfer, and open systems. In driven dissipative nonequilibrium systems, including turbulence, the multiscale energy flux from large scales to small scales helps determine the arrow of time. In addition, open systems are often irreversible due to particle and energy exchanges between the system and the environment. Causality is another important factor that breaks the T symmetry.