bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaving no patient behind! Expert recommendation in the use of innovative technologies for diagnosing rare diseases
Authors: van Karnebeek Clara D. M. , O’Donnell-Luria Anne , Baynam Gareth , Baudot Anaïs , Groza Tudor , Jans Judith J. M. , Lassmann Timo , Letinturier Mary Catherine V. , Montgomery Stephen B. , Robinson Peter N. , Sansen Stefaan , Mehrian-Shai Ruty , Steward Charles , Kosaki Kenjiro , Durao Patricia , Sadikovic Bekim
Published: September 2024

Genetic diagnosis plays a crucial role in rare diseases, particularly with the increasing availability of emerging and accessible treatments. The International Rare Diseases Research Consortium (IRDiRC) has set its primary goal as: “Ensuring that all patients who present with a suspected rare disease receive a diagnosis within one year if their disorder is documented in the medical literature”. Despite significant advances in genomic sequencing technologies, more than half of the patients with suspected Mendelian disorders remain undiagnosed. In response, IRDiRC proposes the establishment of “a globally coordinated diagnostic and research pipeline”. To help facilitate this, IRDiRC formed the Task Force on Integrating New Technologies for Rare Disease Diagnosis. This multi-stakeholder Task Force aims to provide an overview of the current state of innovative diagnostic technologies for clinicians and researchers, focusing on the patient’s diagnostic journey. Herein, we provide an overview of a broad spectrum of emerging diagnostic technologies involving genomics, epigenomics and multi-omics, functional testing and model systems, data sharing, bioinformatics, and Artificial Intelligence (AI), highlighting their advantages, limitations, and the current state of clinical adaption. We provide expert recommendations outlining the stepwise application of these innovative technologies in the diagnostic pathways while considering global differences in accessibility. The importance of FAIR (Findability, Accessibility, Interoperability, and Reusability) and CARE (Collective benefit, Authority to control, Responsibility, and Ethics) data management is emphasized, along with the need for enhanced and continuing education in medical genomics. We provide a perspective on future technological developments in genome diagnostics and their integration into clinical practice. Lastly, we summarize the challenges related to genomic diversity and accessibility, highlighting the significance of innovative diagnostic technologies, global collaboration, and equitable access to diagnosis and treatment for people living with rare disease.
A custom tailored, evidence-based, theory-informed intervention for healthcare professionals to prevent burnout (LAGOM): study protocol for a pragmatic randomized controlled trial
Authors: Koch Anna K. , Schröter Marleen , Berschick Julia , Schiele Julia K. , Bogdanski Martin , Steinmetz Melanie , Stritter Wiebke , Voss Andreas , Seifert Georg , Kessler Christian S.
Published: September 2024

Background

Healthcare professionals in hospitals are exposed to a high level of professional stress, time pressure, workload, and often times poor organizational support. This makes them especially susceptible to burnout. In this pragmatic randomized controlled trial, we test the hypothesis that participation in a 9-week program (LAGOM) that was designed in close collaboration with healthcare professionals, incorporating both individual and organizational aspects reduces emotional exhaustion in healthcare professionals (primary outcome).

Methods

Eighty four nurses and physicians working at the Charité – Universitätsmedizin Berlin and the Immanuel Hospital Berlin are automatically randomized to the LAGOM program (n = 42) or to usual care (n = 42) in a one-to-one allocation rate. The primary outcome emotional exhaustion is measured by the Maslach Burnout Inventory—Human Services Survey at baseline, post-intervention, and 1-month follow-up via an online survey. Secondary outcomes include depersonalization, personal accomplishment, subjective stress, mental well-being, self-care, self-efficacy, working conditions, mindfulness, and adverse events. Electrophysiological measures for heart rate variation analysis are captured. The PRECIS-2 tool is used to characterize the degree of pragmatism in our trial. Data analysis and primary intention-to-treat analysis using repeated measures analysis of variance are performed blind to intervention allocation. Per-protocol, subgroup, and secondary outcome analyses are conducted exploratively. An advisory board consisting of various stakeholders accompanies the study process.

Discussion

If LAGOM proves to be effective in reducing symptoms of burnout, the program could make an important contribution to tackling the problem of the very high burnout rates among healthcare professionals and become an integral part of preventive services offered by hospitals.

Trial registration

German Clinical Trials Register, DRKS00034060. Registered 31 May 2024.
An in vivo tumour organoid model based on the chick embryonic chorioallantoic membrane mimics key characteristics of the patient tissue: a proof-of-concept study
Authors: Benčurová Katarína , Tran Loan , Friske Joachim , Bevc Kajetana , Helbich Thomas H. , Hacker Marcus , Bergmann Michael , Zeitlinger Markus , Haug Alexander , Mitterhauser Markus , Egger Gerda , Balber Theresa
Published: September 2024

Background

Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient – in vitro PDOs – in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns.

Results

The main liver metastasis of the CRC patient exhibited high 2-[18F]FDG uptake and moderate and focal [68Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[18F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient’s liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient’s sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [68Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [68Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking.

Conclusions

We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient’s tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [68Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[18F]FDG was avidly taken up in the patient’s liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients.

Graphical Abstract
Genetic characteristics associated with the virulence of porcine epidemic diarrhea virus (PEDV) with a naturally occurring truncated ORF3 gene
Authors: Lu Ying , Huang Weijian , Lu Zhengpu , Zeng Deping , Yu Kechen , Bai Jiaguo , Qin Qiuying , Long Meijin , Qin Yifeng , Chen Ying , Wei Zuzhang , Ouyang Kang
Published: September 2024

Porcine epidemic diarrhea virus (PEDV) has emerged in American countries, and it has reemerged in Asia and Europe, causing significant economic losses to the pig industry worldwide. In the present study, the 17GXCZ-1ORF3d strain, which has a naturally large deletion at the 172–554 bp position of the ORF3 gene, together with the 17GXCZ-1ORF3c strain, was serially propagated in Vero cells for up to 120 passages. The adaptability of the two strains gradually increased through serial passages in vitro. Genetic variation analysis of the variants of the two strains from different generations revealed that the naturally truncated ORF3 gene in the 17GXCZ-1ORF3d variants was stably inherited. Furthermore, the survival, viral shedding and histopathological lesions following inoculation of piglets demonstrated that the virulence of 17GXCZ-1ORF3d-P120 was significantly attenuated. These results indicate that the naturally truncated ORF3 gene may accelerate the attenuation of virulence and is involved in PEDV virulence together with mutations in other structural genes. Importantly, immunization of sows with G2b 17GXCZ-1ORF3d-P120 increased PEDV-specific IgG and IgA antibody levels in piglets and conferred partial passive protection against heterologous G2a PEDV strains. Our findings suggest that an attenuated strain with a truncated ORF3 gene may be a promising candidate for protection against PEDV.
Energy consumption optimization in green cognitive radio networks based on collaborative spectrum sensing
Authors: Elghamrawy Sally , Ismail Alshimaa H. , Hassanien Aboul Ella
Published: September 2024

In the realm of green communications, the focus is on achieving high spectrum efficiency and low energy consumption. This paper addresses the crucial goal of reducing energy usage in green cognitive radio networks (CRNs) during communication between secondary users (SUs) and primary users (PUs). This paper proposed an energy consumption optimization model (ECOM) for green CRN utilizing collaborative spectrum sensing thereby minimizing the environmental impact and prolonging the operational lifetime of devices. The collaborative spectrum sensing proved its role in optimizing the energy consumption in the green CRN. An energy-efficient scheduling algorithm is implemented in ECOM, in which the SUs can be scheduled to perform their sensing process in a time-division manner to reduce energy consumption. Applied collaborative spectrum sensing serves as a valuable resource for researchers, network operators, and policymakers seeking to balance the increasing demand for wireless communication services with the imperative of sustainability. The simulation results and mathematical proof emphasize that ECOM demonstrates reduced energy usage and increased average effective throughput when compared to other recent models.
Domain knowledge free cloud-IDS with lightweight embedding method
Authors: Kim Yongsik , Park Gunho , Kim Huy Kang
Published: September 2024

The expansion of the cloud computing market has provided a breakthrough in efficiently storing and managing data for individuals and companies. As personal and corporate data move to the cloud, diverse attacks targeting the cloud have also increased for heist beneficial information. Therefore, cloud service providers offer protective environments through diverse security solutions. However, security solutions are limited in preventing advanced attacks because it is challenging to reflect the environment of each user. This paper proposes a Cloud Intrusion Detection System (C-IDS) that adapts to each user’s cloud environment and performs real-time attack detection using Natural Language Processing (NLP). Notably, the C-IDS learns the deployed client environment logs and detects anomalies using the Seq2Seq model with BI-LSTM and Bahdanau attention. We used multiple domain datasets, Linux, Windows, Hadoop, OpenStack, Apache, OpenSSH, and CICIDS2018 to verify the performance of the C-IDS. C-IDS consists of a ‘recognition’ that identifies logs in the deployed environment and a ‘detection’ that discovers anomalies. The recognition results showed an average accuracy of 98.2% for multiple domain datasets. Moreover, the detection results based on the trained model exhibited an average accuracy of 94.2% for the Hadoop, OpenStack, Apache, and CICIDS2018 datasets.
Beyond short-term impact of COVID-19 on transport decarbonization: a scenario analysis of passenger and freight transport by mode in China, 2020–2030
Authors: Li Linna , Loo Becky P. Y.
Published: September 2024

Background

The processes of transport decarbonisation are complicated. In this paper, we adopt the Activity-Modal Share-Energy Intensity-Carbon Intensity of Fuel (ASIF) approach and propose a conceptual framework on the direct and indirect impact of COVID-19 on transport CO2 emissions. In the Chinese context, changes of carbon emissions associated with passenger and freight transport (including urban, rural, and inter-city transport) across different transport modes are estimated. Scenario analysis is then used to estimate the impact of COVID-19 on total transport carbon emissions up to 2030. Four scenarios, from minimal to significant behavioural changes and global recession associated with COVID-19, are generated.

Results

Under the pandemic, the transport system in China was estimated to have produced 28% less CO2 emissions (1044.2 Mt) in 2020, when compared to 2019. Compared with the business-as-usual scenario, the estimated total transport carbon emissions in 2030 would drop by 6%, 15%, and 21% and 23% under the minimal-impact, low-impact, moderate-impact, and severe-impact scenarios, respectively.

Conclusions

The results suggest that the processes triggered by COVID-19 alone will not be sufficient to meet the ambitious transport decarbonisation targets. To meet China’s pledge under the United Nations Framework on Climate Change, the medium-term effects of COVID-19 must be combined with strong transport decarbonisation measures of modal shift and new energy applications. With these additional measures, it may be possible to advance the transport carbon peak before 2030. Lessons are relevant to other developing countries.
Comprehensive antitumor immune response boosted by dual inhibition of SUMOylation and MEK in MYC-expressing KRAS-mutant cancers
Authors: Kotani Hiroshi , Yamano Tomoyoshi , Boucher Justin C. , Sato Shigeki , Sakaguchi Hiroyuki , Fukuda Koji , Nishiyama Akihiro , Yamashita Kaname , Ohtsubo Koushiro , Takeuchi Shinji , Nishiuchi Takumi , Oshima Hiroko , Oshima Masanobu , Davila Marco L. , Yano Seiji
Published: September 2024

Precision medicine has drastically changed cancer treatment strategies including KRAS-mutant cancers which have been undruggable for decades. While intrinsic or acquired treatment resistance remains unresolved in many cases, epigenome-targeted therapy may be an option to overcome. We recently discovered the effectiveness of blocking small ubiquitin-like modifier (SUMO) signaling cascade (SUMOylation) in MYC-expressing KRAS-mutant cancer cells using a SUMO-activating enzyme E inhibitor TAK-981 that results in SUMOylation inhibition. Interestingly, TAK-981 promoted the degradation of MYC via the ubiquitin–proteasome system. Moreover, combination therapy with TAK-981 and MEK inhibitor trametinib remarkably regressed xenografted KRAS-mutant tumors by accumulating DNA damage and inducing apoptosis. Whereas our recent study revealed immune-independent antitumor efficacy, we evaluated the immune responses of cancer cells and immune cells in this study. We found that TAK-981-induced MYC downregulation promoted the activation of STING followed by Stat1 and MHC class I in KRAS-mutant cancer cells. Activation of dendritic cells or T cells treated with TAK-981 was also verified by upregulated activation markers in dendritic cells or skew-toward effector-like phenotypes in T cells. Furthermore, the enhanced immune-dependent antitumor efficacy of the combination therapy with TAK-981 and trametinib was confirmed by infiltration of immune cells into tumor tissues and immunodepleting-test using immunodepleting antibodies in syngeneic immunocompetent mouse models. Together with our recent study and here, the findings support that combination inhibition of SUMOylation and MEK comprehensively conquers MYC-expressing KRAS-mutant cancers by both immune-dependent and immune-independent antitumor responses.
A feasibility trial of olanzapine for young people with Anorexia Nervosa (OPEN): clinicians’ perspectives
Authors: Kellermann Vanessa , Sengun Filiz Ece , Said Olena , Bentley Jessica , Khor Joel W.T. , Simic Mima , Nicholls Dasha , Treasure Janet , Schmidt Ulrike , Himmerich Hubertus , Lawrence Vanessa
Published: September 2024

Background

The OPEN feasibility trial testing olanzapine in anorexia nervosa (AN) in young people (YP) was not successful due to poor recruitment. This study aims to understand clinicians’ views and experiences of using olanzapine in AN and the challenges in implementing the trial in National Health Service (NHS) clinical settings.

Methods

We conducted qualitative interviews with eating disorders (ED) clinicians involved with the study (n = 11). Framework analysis was applied to qualitative data to identify barriers and facilitators to recruitment and study implementation. A web-based semi-structured Qualtrics survey was administered to ED clinicians (n = 24). Findings from the survey were used to corroborate and expand on the information derived from qualitative interviews.

Results

Qualitative analysis identified four main themes: (1) Acknowledging Service User (SU) / Family Concerns, (2) Prioritising person-centred care, (3) Limited Service Capacity and (4) Study eligibility criteria. Subthemes are outlined accordingly. Clinicians appeared confident addressing SU concerns around olanzapine in clinical discussions, but timing was critical, and olanzapine was considered one aspect of treatment that needed to align with their holistic approach. Service pressures restricted opportunities for recruitment and the ability to offer regular review. At the same time, some YP were ineligible for the trial, as they were already taking olanzapine, or needed to be prescribed it more promptly than the study procedures allowed. Survey findings underlined confidence in prescribing and informing on olanzapine, the various possible benefits of olanzapine besides weight gain, and the importance of therapeutic alliances and informed consent. Both data sets highlight the need for further evidence on long-term safety, side effects and efficacy of olanzapine use for AN. Where clinical service capacity is at a premium, research implementation is not prioritised, particularly in intensive clinical settings.

Conclusions

Findings provide first-hand insight into individual and systemic challenges with research implementation in the NHS, which need to be considered when designing future clinical research studies. We emphasise a person-centred approach when discussing olanzapine to consider a holistic recovery from AN beyond weight-gain as an isolated outcome for improvement.
Inhibitory control and academic achievement – a study of the relationship between Stroop Effect and university students’ academic performance
Authors: Dvorak Martin
Published: September 2024

While previous research has identified executive functions as predictors of academic performance in school children, similar studies conducted among adults show mixed results. One of the reasons given for executive functions having a limited effect on academic achievements in adulthood is that they are usually fully developed by that time. Since these executive functions are at their peak at that age, the individual differences in these as well as their influence on academic performance in adults are harder to trace. The paper describes a study conducted among 107 university students the goal of which was to find out whether there is any relationship between the adult students’ inhibitory control values measured with the Stroop Test and their academic achievements. Although the results indicate a weak correlation between the Stroop Effect and the students’ academic performance of low statistical significance, which seems to confirm the outcomes of the previous studies focusing on adults, the study reveals an unexpected statistically significant correlation between the students’ grade averages and the number of their incorrect color identifications. This phenomenon appears to be worth pursuing in future research since it suggests the existence of another, relatively quickly measurable, variable possibly reflecting other predictors of academic performance in adults such as a degree of their manifested conscientiousness, their ability to concentrate on an assigned, relatively short, one-off task and their attitude to fulfilling this task. The Stroop Test, despite not being originally designed for this purpose, might thus be used as a simple tool suitable for providing information about these variables via the subject’s number of color identification errors. Such information can subsequently inform the activities that educators may include in their curricula to foster conscientiousness and concentration in the students lacking these.
New norm values of the brief resilience scale (BRS) from the German general population with new post-COVID-19 data
Authors: Rösner Christoph , Brähler Elmar , Sachser Cedric , Clemens Vera , Petrowski Katja
Published: September 2024

Background

The concept of psychological resilience has spurred extensive research across various fields, with the Brief Resilience Scale (BRS) emerging as a concise tool to measure an individual’s ability to rebound from stress. It has been translated into multiple languages, including German, but the validation of the German version occurred prior to the COVID-19 pandemic. Therefore, the main objective of this study was to examine new norm values and psychometric properties of the BRS.

Methods

Norm values, the factor structure, reliability and validity of the BRS were examined using data from a representative survey of the German general population (N = 2522).

Results

The results indicated that the method-factor model showed the best fit, suggesting a nuanced understanding of resilience beyond a single-factor approach. The BRS demonstrated good convergent and discriminant validity based on both latent and manifest correlations. Moreover, the study revealed increasing postpandemic resilience scores.

Conclusions

The results of this study provide support for the psychometric reliability and validity of the German version of the BRS after the COVID-19 pandemic and underscore the importance of assessing resilience amidst evolving societal challenges and highlight the need for further exploration in diverse populations.
The significant others of aurora kinase a in cancer: combination is the key
Authors: Nikhil Kumar , Shah Kavita
Published: September 2024

AURKA is predominantly famous as an essential mitotic kinase. Recent findings have also established its critical role in a plethora of other biological processes including ciliogenesis, mitochondrial dynamics, neuronal outgrowth, DNA replication and cell cycle progression. AURKA overexpression in numerous cancers is strongly associated with poor prognosis and survival. Still no AURKA-targeted drug has been approved yet, partially because of the associated collateral toxicity and partly due to its limited efficacy as a single agent in a wide range of tumors. Mechanistically, AURKA overexpression allows it to phosphorylate numerous pathological substrates promoting highly aggressive oncogenic phenotypes. Our review examines the most recent advances in AURKA regulation and focuses on 33 such direct cancer-specific targets of AURKA and their associated oncogenic signaling cascades. One of the common themes that emerge is that AURKA is often involved in a feedback loop with its substrates, which could be the decisive factor causing its sustained upregulation and hyperactivation in cancer cells, an Achilles heel not exploited before. This dynamic interplay between AURKA and its substrates offers potential opportunities for targeted therapeutic interventions. By targeting these substrates, it may be possible to disrupt this feedback loop to effectively reverse AURKA levels, thereby providing a promising avenue for developing safer AURKA-targeted therapeutics. Additionally, exploring the synergistic effects of AURKA inhibition with its other oncogenic and/or tumor-suppressor targets could provide further opportunities for developing effective combination therapies against AURKA-driven cancers, thereby maximizing its potential as a critical drug target.
Oncogenic ACSM6 impairs CD8+ T cell-based immune response in bladder cancer
Authors: Nie Zhenyu , Liu Bolong , Liu Jinhui , Zu Xiongbing , Wang Juanhua , Chen Jinbo , Fan Benyi , Deng Dingshan
Published: September 2024

Resistance to immunotherapy in bladder cancer has greatly limited its clinical application. Through single-cell sequencing, we determined that ACSM6, an oncogene that is highly expressed in bladder cancer, promotes the abilities of proliferation, cloning, migration, and invasion. The key point is that ACSM6 can also lead to a non-inflammatory immune microenvironment by inhibiting the chemotaxis and tumor killing ability of CD8+ T cells. Survival analysis revealed that high ACSM6 expression was associated with shorter overall survival in the immunotherapy cohort. In summary, ACSM6 is expected to become a novel biomarker for predict bladder cancer progression.
Antioxidant properties of lemon essential oils: a meta-analysis of plant parts, extraction methods, dominant compounds, and antioxidant assay categories
Authors: Budiarto Rahmat , Khalisha Ana , Sari Dwi Novanda , Ujilestari Tri , Wahyono Teguh , Azmi Amirul Faiz Mohd , Adli Danung Nur , Lusiana Evellin Dewi , Sitaresmi Pradita Iustitia , Sholikin Mohammad Miftakhus
Published: September 2024

Recent studies have explored the antioxidant properties of lemon essential oil (LEO), taking considering factors like plant part, extraction methods, and antioxidant assay. However, due to varied results and limited precision in individual studies, our meta-analysis aims to offer a comprehensive understanding across different experiments, irrespective of location or time. Out of 109 scientific articles published between 1947 and 2024, only 28 successfully validated their data on differences in antioxidant capacity and IC50, using weighted averages of Hedges’ d in meta-analysis. A meta-analysis revealed several key findings: (i) lemon leaf and peel extracts have higher IC50 compared to controls, whereas whole plant extracts show lower values (p < 0.001); (ii) the maceration preserves antioxidant properties better than hydro-distillation and Soxhlet extraction (p < 0.001); (iii) LEO require higher concentrations to achieve comparable free radical inhibition as the standard controls such as AsA, BHT, and quercetin, suggesting lower antioxidant efficiency. This was supported by IC50 result, which showed no significant difference between LEO and other compounds like thymol, Thymus vulgaris EO, and Citrus aurantium EO. However, compared to AsA, BHT, limonene, and trolox, the inhibition efficacy was significantly lower (p < 0.01). These findings consistently demonstrated significant antioxidant activity across multiple assays, including ABTS, β-carotene bleaching, DPPH, and FRAP (p < 0.01). Notably, the predominant components of LEO including α-linoleic acid, D-limonene, limonene, L-limonene, neryl acetate, sabinene, and Z-citral, which demonstrate significant potency as antioxidant agent (p < 0.01). Specifically, limonene and Z-citral make substantial contributions to its antioxidant capacity (p < 0.01). Despite variations in purity among LEO extractions, there is potential for future enhancement through nanoemulsion. In conclusion, LEO show promise as an alternative antioxidant, with emphasis to selecting samples based on leaves or peels and employing maceration extractions for various antioxidant assays. Active components rich in terpenoids, such as limonene and Z-citral, are particularly noteworthy.

Graphical Abstract
Impact of the transpulmonary pressure on right ventricle impairment incidence during acute respiratory distress syndrome: a pilot study in adults and children
Authors: Vedrenne-Cloquet Meryl , Petit Matthieu , Khirani Sonia , Charron Cyril , Khraiche Diala , Panaioli Elena , Habib Mustafa , Renolleau Sylvain , Fauroux Brigitte , Vieillard-Baron Antoine
Published: September 2024

Background

Right ventricle impairment (RVI) is common during acute respiratory distress syndrome (ARDS) in adults and children, possibly mediated by the level of transpulmonary pressure (PL). We sought to investigate the impact of the level of PL on ARDS-associated right ventricle impairment (RVI).

Methods

Adults and children (> 72 h of life) were included in this two centers prospective study if they were ventilated for a new-onset ARDS or pediatric ARDS, without spontaneous breathing and contra-indication to esophageal catheter. Serial measures of static lung, chest wall, and respiratory mechanics were coupled to critical care echocardiography (CCE) for 3 days. Mixed-effect logistic regression models tested the impact of lung stress (ΔPL) along with age, lung injury severity, and carbon dioxide partial pressure, on RVI using two definitions: acute cor pulmonale (ACP), and RV dysfunction (RVD). ACP was defined as a dilated RV with septal dyskinesia; RVD was defined as a composite criterion using tricuspid annular plane systolic excursion, S wave velocity, and fractional area change.

Results

46 patients were included (16 children, 30 adults) with 106 CCE (median of 2 CCE/patient). At day one, 19% of adults and 4/7 children > 1 year exhibited ACP, while 59% of adults and 44% of children exhibited RVD. In the entire population, ACP was present on 17/75 (23%) CCE. ACP was associated with an increased lung stress (mean ΔPL of 16.2 ± 6.6 cmH2O in ACP vs 11.3 ± 3.6 cmH2O, adjusted OR of 1.33, CI95% [1.11–1.59], p = 0.002) and being a child. RVD was present in 59/102 (58%) CCE and associated with lung stress. In children > 1 year, PEEP was significantly lower in case of ACP (9.3 [8.6; 10.0] cmH2O in ACP vs 15.0 [11.9; 16.3] cmH2O, p = 0.03).

Conclusion

Lung stress was associated with RVI in adults and children with ARDS, children being particularly susceptible to RVI.

Trial registration Clinical trials identifier: NCT0418467.
Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts
Authors: Han Han , Jia Hao , Wang Yi-Fan , Song Jiang-Ping
Published: September 2024

The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth’s magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth’s rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.
Assessment of porcine reproductive and respiratory syndrome virus (PRRSV) farm surface contamination through environmental sampling
Authors: Melini Claudio Marcello , Kikuti Mariana , Bruner Laura , Allerson Matt , O’Brien Katie , Stahl Chase , Roggow Brian , Yeske Paul , Leuwerke Brad , Schwartz Mark , Torremorell Montserrat , Corzo Cesar A.
Published: September 2024

Background

During the fall of 2020, the porcine reproductive and respiratory syndrome virus (PRRSV) L1C.5 variant emerged and rapidly spread throughout southern Minnesota generating questions regarding possible transmission routes. This study aimed to investigate whether PRRSV could be detected on surfaces inside and outside pig barns housing L1C.5 variant PRRSV-positive pigs to illustrate the potential for indirect transmission of PRRSV. Seven Midwestern U.S. PPRS-positive breeding or growing pig farms and one PRRS-negative farm were conveniently selected. Internal and external barn surfaces were wiped using a PBS moistened cloth and the resulting liquid was submitted to the University of Minnesota Veterinary Diagnostic Laboratory for PRRSV RT-PCR testing and virus isolation.

Results

All (n = 26) samples from PRRSV-negative farm tested negative. Nineteen (13%) out of 143 samples from positive farms yielded positive RT-PCR results. Positive samples originated primarily from exhaust fan cones and doorknobs, followed by anteroom floor and mortality carts/sleds. Virus isolation attempted on two samples did not yield positive results.

Conclusions

PRRSV contamination can occur on surfaces inside and outside pig barns that are in frequent contact with farm personnel. Although virus isolation attempts were negative, our results illustrate the potential for PRRSV to be transmitted indirectly through contaminated materials or farm personnel. The study supports the implementation of biosecurity practices by farm personnel to prevent the introduction of PRRSV into farms and the prevention of PRRSV transmission between farms.
Synthesized economic evidence on the cost-effectiveness of screening familial hypercholesterolemia
Authors: Wang Mengying , Jiang Shan , Li Boyang , Parkinson Bonny , Lu Jiao , Tan Kai , Gu Yuanyuan , Li Shunping
Published: September 2024

Background

Familial hypercholesterolemia (FH) is a prevalent genetic disorder with global implications for severe cardiovascular diseases. Motivated by the growing recognition of the need for early diagnosis and treatment of FH to mitigate its severe consequences, alongside the gaps in understanding the economic implications and equity impacts of FH screening, this study aims to synthesize the economic evidence on the cost-effectiveness of FH screening and to analyze the impact of FH screening on health inequality.

Methods

We conducted a systematic review on the economic evaluations of FH screening and extracted information from the included studies using a pre-determined form for evidence synthesis. We synthesized the cost-effectiveness components involving the calculation of synthesized incremental cost-effectiveness ratios (ICERs) and net health benefit (NHB) of different FH screening strategies. Additionally, we applied an aggregate distributional cost-effectiveness analysis (DCEA) to assess the impact of FH screening on health inequality.

Results

Among the 19 studies included, over half utilized Markov models, and 84% concluded that FH screening was potentially cost-effective. Based on the synthesized evidence, cascade screening was likely to be cost-effective, with an ICER of $49,630 per quality-adjusted life year (QALY). The ICER for universal screening was $20,860 per QALY as per evidence synthesis. The aggregate DCEA for six eligible studies presented that the incremental equally distributed equivalent health (EDEH) exceeded the NHB. The difference between EDEH and NHB across the six studies were 325, 137, 556, 36, 50, and 31 QALYs, respectively, with an average positive difference of 189 QALYs.

Conclusions

Our research offered valuable insights into the economic evaluations of FH screening strategies, highlighting significant heterogeneity in methods and outcomes across different contexts. Most studies indicated that FH screening is cost-effective and contributes to improving overall population health while potentially reducing health inequality. These findings offer implications that policies should promote the implementation of FH screening programs, particularly among younger population. Optimizing screening strategies based on economic evidence can help identify the most effective measures for improving health outcomes and maximizing cost-effectiveness.
Exploring the factors influencing the health-related quality of life in patients experiencing adverse drug reactions: a cross-sectional study
Authors: Pavan Garapati , Kumar Manish , Murti Krishna , Dhingra Sameer , Ravichandiran V.
Published: September 2024

Background

This study aimed to assess the factors influencing health-related quality of life (HRQoL) in patients experiencing adverse drug reactions (ADRs) at a tertiary care public sector hospital. A cross-sectional study was conducted over a period of 18 months, and included both male and female patients aged 18 years and above. Patients who visited the outpatient and inpatient departments with complaints associated with ADRs were included in this study. HRQoL data were collected using the EuroQol—5 Dimension—5 Level (EQ-5D-5L) questionnaire to assess five dimensions of health on a five-level scale. Descriptive statistics, t-tests, and analysis of variance were used to analyze the data. Multivariate regression analysis was performed to identify the potential determinants of HRQoL.

Results

A total of 316 patients were included in the study among these participants, of which 54% were female, and 65% were from rural areas. The majority (68%) of the patients had moderately severe ADRs, and 63% of the participants had an income < 2.5 lakh Indian rupees (3009 USD). The mean EQ-5D-5L and EuroQoL Visual Analog Scale (EQ VAS) scores of the study participants were 0.714 and 69.73, respectively. The variables ADR severity, income, and age showed a significant difference (p < 0.05) in HRQoL.

Conclusion

This study provides insights into HRQoL among patients with ADRs and identifies the determinants of HRQoL. The findings of this study will contribute to improving patient-centered care and optimizing patient outcomes.
Advancements and challenges in gastric cancer: epidemiology, biomarkers, and therapeutic strategies
Authors: Nishimuni Marina , Claro Laura Carolina Lopez , Braghiroli Maria Ignez Freitas Melro
Published: September 2024

Gastric cancer is the fifth most common cause of cancer-related deaths globally, with a decreasing but still high number of cases. Although there have been improvements in treatment choices, the expected survival rates have not yet been achieved. In addition to the challenges associated with developing effective therapies, there is an urgent need to establish diagnostic and predictive biomarkers to guide treatment selection. Therefore, this review summarizes key aspects of gastric cancer, including its epidemiology, associated risk factors, and underlying pathogenesis. It also discusses the main biomarkers involved in this disease, such as PD-L1, HER − 2, Epstein-Barr virus (EBV), Claudin 18.2, FGFR2, and the current standard and targeted therapies. Molecular testing for these changes is gaining significance in the context of gastric cancer. By incorporating detailed biomarker analysis into clinical practice, we can provide more effective and personalized treatment options, ultimately improving clinical management and enhancing survival rates for gastric cancer patients.
Gout comorbidities: results from the Korean National Health and Nutrition Examination Survey
Authors: Jeong Hyemin , Chang Young-Soo , Jeon Chan Hong
Published: September 2024

Objectives

Gout is associated with several comorbidities. This study aimed to evaluate the prevalence of comorbidities in the Korean adult population with gout and investigated the association of gout with these comorbidities.

Methods

Data from 15,935 (weighted n = 39,049,167) participants aged 19 years and older in the Korean National Health and Nutrition Examination Survey from 2019 to 2021 were used for analysis. Weighted prevalence and odds ratios (OR) of comorbidities in individuals with gout were compared to a non-gout population.

Results

The weighted prevalence of gout was 2.1% (weighted n = 808,778). Among individuals with gout, 66.5% had metabolic syndrome, 54.9% had hypertension, 41.2% had hypercholesterolemia, 19.1% had diabetes, 13.5% had chronic kidney disease (CKD), 4.1% had myocardial infarction or angina, 3.8% had stroke, and 2.8% had rheumatoid arthritis (RA). After adjusting for socioeconomic and lifestyle characteristics, gout was independently associated with the increased prevalence of metabolic syndrome (male OR = 2.0, 95% confidence interval (CI): 1.5–2.8; female OR = 3.7, 95% CI: 1.5–9.2), hypercholesterolemia (male OR = 1.9, 95% CI: 1.4–2.5; female OR = 3.1, 95% CI: 1.3–7.5), CKD (male OR = 4.5, 95% CI: 2.7–7.3; female OR = 11.5, 95% CI: 4.1–32.1), and RA (male OR = 2.8, 95% CI: 1.1–7.1; female OR = 3.1, 95% CI: 1.1–8.7) compared to the non-gout population.

Conclusions

Gout was associated with several comorbidities, including RA, in both males and females. These results suggest that the prevention and treatment of comorbidities at the individual level, carried out by clinicians, and knowledge of these comorbidities would help guide health policies for the Korean population.
Exhaustive computational studies on pyrimidine derivatives as GPR119 agonist for the development of compounds against NIDDM
Authors: Nema Priyanshu , Agarwal Shivangi , Kori Shivam Kumar , Kumar Ajay , Kashaw Varsha , Iyer Arun K. , Kashaw Sushil Kumar
Published: September 2024

Background

Type-2 Diabetes (T2DM) is a long-term medical disorder characterized by Insulin deficiency and high blood glucose levels. Among other medications to cure T2DM, the review of the literature found that various Pyrimidine derivatives act as an agonist for G-protein-coupled receptor 119 (GPR119) was proposed to control blood glucose levels by enhancing the function of pancreatic Beta-cells and its mechanism of action with fewer adverse effects. In the present research work, In-silico investigations were carried out to investigate the potential of the Pyrimidine analog as an agonist to the protein target GPR119 receptor. We performed exhaustive molecular modeling and protein modeling methodologies such as homology modeling, and molecular docking along with various drug designing tools such as 3D-QSAR and Pharmacophore Mapping to ascertain the design of better GPR119 agonists.

Results

Based on in-depth computational studies, we designed new pyrimidine moiety and analyzed them for GPR119 receptor agonist and further explored the ADMET properties. Designed compounds were found to exhibit better-predicted activities as compared to reference compound.

Conclusions

The current research on pyrimidine derivatives, using molecular docking, 3D-QSAR and Pharmacophore mapping demonstrated that the obtained computational model has significant properties and the designed molecules and Dataset from this model, produced antidiabetic compound against the target GPR119 i.e., compound 1S, 1Z and 1D with the docking score of − 11.696, − 9.314 and − 8.721, respectively. The pharmacokinetics and drug-likeness studies revealed that these compounds may be the future candidates for the treatment of diabetes acting via the GPR119 agonist mechanism.
Weather or Not
Authors: Duffy Andrea
Published: September 2024

This article introduces the field of climate history and highlights its connections to agricultural history and other historical subdisciplines. It is designed for historians curious about past climates and climate change and how this information might inform their work. It defines climate history and historical climatology, surveys the state of climate historiography, and provides an overview of the field's research methods and challenges, emphasizing the varied, interdisciplinary nature of its sources. This methodological review exposes the value and limitations of natural archives such as tree rings (dendroclimatology), and it presents human records as a complementary and underutilized source of paleoclimatological data that historians are well positioned to develop. It demonstrates that climate history offers a useful and accessible lens for interpreting the past and contextualizing contemporary social and environmental issues. Finally, it encourages historians to actively consider the climate, and it provides suggestions and resources for getting started.
Introduction
Authors: Ron Ariel
Published: September 2024

Agricultural policy in the United States is made through a distinctive coalition of interests that come together every five years or so to craft the so-called farm bill. The core of this coalition is a tacit trade of subsidies for agricultural commodity growers in exchange for food and nutrition programs for the needy. How has this coalition proved so durable and adaptable over the years? Or has it, in fact, changed in fundamental ways? Will future policy that confronts agriculture's significant contribution to greenhouse gas emissions take a different form? These questions motivate the forum's return to a venerable concept in agricultural history and social science: the “iron triangle,” which refers to a mutually supporting arrangement of legislators, bureaucrats, and special interests. This essay introduces and synthesizes contributors’ efforts to interrogate and apply the iron triangle concept, finding that it retains utility for understanding the challenges that will face a climate-oriented farm bill politics.
Research Note: The Association Between Parity and Odds of Alzheimer's Disease and Dementias Status
Authors: Zhang Yan , Fletcher Jason M.
Published: September 2024

While parity is a significant factor influencing parental health, its relationship with dementia remains underexplored. This research note advances the literature by conducting a well-powered analysis of associations between parity (i.e., number of children) and Alzheimer's disease and dementias (AD/D) status in large-scale population data. The data contain a large number of AD/D cases (37,228 women and 19,846 men), allowing a range (1–10) of parity associations to be estimated precisely. Using proxy (adult child's) reports of parental AD/D status, we find that both fathers and mothers with grand multiparity have decreased odds of AD/D status, and the effect sizes become larger as parity increases, with 30–40% reduction in AD/D status at parities above 7. The association is stronger for mothers than for fathers. This finding differs from much of the prior literature and likely suggests the impact of parity, as one of the important life course contexts, on people's cognitive function and risk of having AD/D. Finally, we include population projections that consider how large changes in parity distributions over time may contribute to small elevations in AD/D rates.