bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma
Authors: Cai Zhimou , Chen Lin , Chen Siyu , Fang Ruihua , Chen Xiaolin , Lei Wenbin
Published: October 2023

Background

Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among all head-and-neck cancers, and treatment options are limited. Tumor microenvironment (TME) analysis can help identify new therapeutic targets and combined treatment strategies.

Methods

Six primary HPSCC tissues and two adjacent normal mucosae from six treatment-naïve patients with HPSCC were analyzed using scRNA-seq. Cell types were curated in detail, ecosystemic landscapes were mapped, and cell–cell interactions were inferred. Key results were validated with The Cancer Genome Atlas and cell biology experiments.

Results

Malignant HPSCC epithelial cells showed significant intratumor heterogeneity. Different subtypes exhibited distinct histological features, biological behaviors, and spatial localization, all affecting treatment selection and prognosis. Extracellular matrix cancer-associated fibroblasts (mCAFs) expressing fibroblast activation protein were the dominant CAFs in HPSCC tumors. mCAFs, constituting an aggressive CAF subset, promoted tumor cell invasion, activated endothelial cells to trigger angiogenesis, and synergized with SPP1+ tumor associated macrophages to induce tumor progression, ultimately decreasing the overall survival of patients with HPSCC. Moreover, the LAMP3+ dendritic cell subset was identified in HPSCC and formed an immunosuppressive TME by recruiting Tregs and suppressing CD8+ T cell function.

Conclusions

mCAFs, acting as the communication center of the HPSCC TME, enhance the invasion ability of HPSCC cells, mobilizing surrounding cells to construct a tumor-favorable microenvironment. Inhibiting mCAF activation offers a new anti-HPSCC therapeutic strategy.

Graphical Abstract
Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis
Authors: Wang Yi , Zhu Gui-Qi , Yang Rui , Wang Cheng , Qu Wei-Feng , Chu Tian-Hao , Tang Zheng , Yang Chun , Yang Li , Zhou Chang-Wu , Miao Geng-Yun , Liu Wei-Ren , Shi Ying-Hong , Zeng Meng-Su
Published: October 2023

Background and aims

The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features.

Methods

Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO.

Results

Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs.

Conclusion

This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.
BRAF D594A mutation defines a unique biological and immuno-modulatory subgroup associated with functional CD8+ T cell infiltration in colorectal cancer
Authors: Li Wenjing , Zhao Chenyi , Li Wenhui , Gong Yang , Ma Kaili , Lu Yujie , Liu Xiaowei , Zhang Lianjun , Guo Feng
Published: October 2023

Background

BRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells.

Methods

BRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 assay, Annexin V/PI staining and transwell assay. The concentrations of soluble cytokines were detected by ELISA. The membrane expression of immuno-modulatory molecules and the pattern of tumor infiltrating lymphocyte were evaluated by flow cytometry. The molecular mechanism was explored by RNA sequencing. Immunohistochemistry (IHC) staining was used for the detection of CD8α in tumor tissues. qRT-PCR and western blot were performed to assess the mRNA and protein expression. Anti-PD-L1 treatment and cytokines neutralization experiments were conducted in in vivo models.

Results

D594A mutant cells displayed lower grade malignancy characteristics than V600E (class I) and G469V (class II) mutant cells. Meanwhile, D594A mutation led to evident immuno-modulatory features including upregulation of MHC Class I and PD-L1. In vivo experiments displayed that the frequency of infiltrated CD8+ T cells was significantly high within D594A mutant tumors, which may provide potential response to anti-PD-L1 therapy. RNA sequencing analysis showed that D594A mutation led to enhanced expression of ATF3 and THBS1, which thus facilitated CXCL9 and CXCL10 production upon IFN-γ treatment. In addition, CXCL9 or CXCL10 neutralization reduced the infiltration of CD8+ T cells into THBS1-overexpressing tumors.

Conclusions

D594A mutant CRC exhibited lower aggressiveness and immune-activated phenotype. ATF3-THBS1-CXCL9/CXCL10 axis mediated functional CD8+ T cells infiltration into the microenvironment of D594A mutant CRC. Our present study is helpful to define this mutation in CRC and provide important insights in designing effective immunotherapeutic strategies in clinic.
RIZ2 at the crossroad of the EGF/EGFR signaling in colorectal cancer
Authors: Di Donato Marzia , Di Zazzo Erika , Salvati Annamaria , Sorrentino Carmela , Giurato Giorgio , Fiore Donatella , Proto Maria Chiara , Rienzo Monica , Casamassimi Amelia , Gazzerro Patrizia , Bifulco Maurizio , Castoria Gabriella , Weisz Alessandro , Nassa Giovanni , Abbondanza Ciro
Published: October 2023

Background

Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options, CRC shows a poor prognosis with a 5 year survival rate of ~ 45%. PRDM2/RIZ, a member of PR/SET domain family (PRDM), expresses two main molecular variants, the PR-plus isoform (RIZ1) and the PR-minus (RIZ2). The imbalance in their expression levels in favor of RIZ2 is observed in many cancer types. The full length RIZ1 has been extensively investigated in several cancers where it acts as a tumor suppressor, whereas few studies have explored the RIZ2 oncogenic properties. PRDM2 is often target of frameshift mutations and aberrant DNA methylation in CRC. However, little is known about its role in CRC.

Methods

We combined in-silico investigation of The Cancer Genome Atlas (TCGA) CRC datasets, cellular and molecular assays, transcriptome sequencing and functional annotation analysis to assess the role of RIZ2 in human CRC.

Results

Our in-silico analysis on TCGA datasets confirmed that PRDM2 gene is frequently mutated and transcriptionally deregulated in CRC and revealed that a RIZ2 increase is highly correlated with a significant RIZ1 downregulation. Then, we assayed several CRC cell lines by qRT-PCR analysis for the main PRDM2 transcripts and selected DLD1 cell line, which showed the lowest RIZ2 levels. Therefore, we overexpressed RIZ2 in these cells to mimic TCGA datasets analysis results and consequently to assess the PRDM2/RIZ2 role in CRC. Data from RNA-seq disclosed that RIZ2 overexpression induced profound changes in CRC cell transcriptome via EGF pathway deregulation, suggesting that RIZ2 is involved in the EGF autocrine regulation of DLD1 cell behavior. Noteworthy, the forced RIZ2 expression increased cell viability, growth, colony formation, migration and organoid formation. These effects could be mediated by the release of high EGF levels by RIZ2 overexpressing DLD1 cells.

Conclusions

Our findings add novel insights on the putative RIZ2 tumor-promoting functions in CRC, although additional efforts are warranted to define the underlying molecular mechanism.
Motor-cognitive functions required for driving in post-stroke individuals identified via machine-learning analysis
Authors: Tabuchi Genta , Furui Akira , Hama Seiji , Yanagawa Akiko , Shimonaga Koji , Xu Ziqiang , Soh Zu , Hirano Harutoyo , Tsuji Toshio
Published: October 2023

Background

People who were previously hospitalised with stroke may have difficulty operating a motor vehicle, and their driving aptitude needs to be evaluated to prevent traffic accidents in today’s car-based society. Although the association between motor-cognitive functions and driving aptitude has been extensively studied, motor-cognitive functions required for driving have not been elucidated.

Methods

In this paper, we propose a machine-learning algorithm that introduces sparse regularization to automatically select driving aptitude-related indices from 65 input indices obtained from 10 tests of motor-cognitive function conducted on 55 participants with stroke. Indices related to driving aptitude and their required tests can be identified based on the output probability of the presence or absence of driving aptitude to provide evidence for identifying subjects who must undergo the on-road driving test. We also analyzed the importance of the indices of motor-cognitive function tests in evaluating driving aptitude to further clarify the relationship between motor-cognitive function and driving aptitude.

Results

The experimental results showed that the proposed method achieved predictive evaluation of the presence or absence of driving aptitude with high accuracy (area under curve 0.946) and identified a group of indices of motor-cognitive function tests that are strongly related to driving aptitude.

Conclusions

The proposed method is able to effectively and accurately unravel driving-related motor-cognitive functions from a panoply of test results, allowing for autonomous evaluation of driving aptitude in post-stroke individuals. This has the potential to reduce the number of screening tests required and the corresponding clinical workload, further improving personal and public safety and the quality of life of individuals with stroke.
Dysregulation of intracellular redox homeostasis by the SARS-CoV-2 ORF6 protein
Authors: De Angelis Marta , Anichini Gabriele , Palamara Anna Teresa , Nencioni Lucia , Gori Savellini Gianni
Published: October 2023

SARS-CoV-2 has evolved several strategies to overcome host cell defenses by inducing cell injury to favour its replication. Many viruses have been reported to modulate the intracellular redox balance, affecting the Nuclear factor erythroid 2-Related Factor 2 (NRF2) signaling pathway. Although antioxidant modulation by SARS-CoV-2 infection has already been described, the viral factors involved in modulating the NRF2 pathway are still elusive. Given the antagonistic activity of ORF6 on several cellular pathways, we investigated the role of the viral protein towards NRF2-mediated antioxidant response. The ectopic expression of the wt-ORF6 protein negatively impacts redox cell homeostasis, leading to an increase in ROS production, along with a decrease in NRF2 protein and its downstream controlled genes. Moreover, when investigating the Δ61 mutant, previously described as an inactive nucleopore proteins binding mutant, we prove that the oxidative stress induced by ORF6 is substantially related to its C-terminal domain, speculating that ORF6 mechanism of action is associated with the inhibition of nuclear mRNA export processes. In addition, activation by phosphorylation of the serine residue at position 40 of NRF2 is increased in the cytoplasm of wt-ORF6-expressing cells, supporting the presence of an altered redox state, although NRF2 nuclear translocation is hindered by the viral protein to fully antagonize the cell response. Furthermore, wt-ORF6 leads to phosphorylation of a stress-activated serine/threonine protein kinase, p38 MAPK, suggesting a role of the viral protein in regulating p38 activation. These findings strengthen the important role of oxidative stress in the pathogenesis of SARS-CoV-2 and identify ORF6 as an important viral accessory protein hypothetically involved in modulating the antioxidant response during viral infection.
Traditional medical practices for children in five islands from the Society archipelago (French Polynesia)
Authors: Chassagne François , Butaud Jean-François , Ho Raimana , Conte Eric , Hnawia Édouard , Raharivelomanana Phila
Published: October 2023

Background

Traditional Polynesian medicine for children has been poorly documented, and few data are available on their efficacy and safety. In this context, the aim of this study was to identify traditional practices used for treating children and then assess the efficacy and safety of the most cited remedies by reviewing the literature.

Methods

In 2022, a semi-structured survey was carried out on five islands from the Society archipelago (Bora Bora, Huahine, Moorea, Raiatea, and Tahiti). A total of 86 participants were interviewed including 19 experts in herbalism. A thorough literature review was performed on the most cited plant species to gather the relevant ethnobotanical, pharmacological, and clinical data of each remedy.

Results

Participants mentioned using 469 remedies to treat 69 health disorders. The most represented health categories were digestive system, skin disorders, infectious diseases, and respiratory system. A total of 67 plant species (representing 731 use-reports) were mentioned and Annona muricata, Gardenia taitensis, and Hibiscus rosa-sinensis were the main plants reported. Regarding the safety of cited remedies, one plant (Microsorum grossum) showed high risk of toxicity, and its use should be avoided in infants and children.

Conclusion

Our survey confirms the importance of traditional medical practices for children in the Society Islands. A lack of data in children for most cited remedies demonstrate the need for more pharmacological and toxicological research on Polynesian medicinal plants. Finally, the potential risk of toxicity for some cited plant species reported calls for a better information of traditional medicine users and healers.
Avian Plasmodium spp. and Haemoproteus spp. parasites in mosquitoes in Germany
Authors: Köchling Katharina , Schaub Günter A. , Werner Doreen , Kampen Helge
Published: October 2023

Background

Although haemosporidian parasites may cause considerable health and economic problems in aviaries, there is limited understanding of the vectors transmitting them. Mosquito-borne Plasmodium species are responsible for the deaths of numerous exotic (= immunologically naïve) birds in zoos every year, while native birds are adapted to the parasites and largely protected by an effective immune response.

Methods

Mosquitoes were collected in bird/animal parks, wetlands and private gardens in various regions of Germany from 2020 to 2022. Females were pooled with up to 10 specimens according to taxon, location and date. Extracted DNA was screened for avian Haemosporida-specific mitochondrial rDNA using real-time polymerase chain reaction (PCR). Positive samples were amplified by a Plasmodium/Haemoproteus-specific nested PCR targeting the partial cytochrome b gene, followed by sequencing of the PCR product for species identification. Sequences were checked against GenBank and MalAvi databases.

Results

PCR of 2633 pools with 8834 female mosquitoes signalled infection with Plasmodium in 46 pools and with Haemoproteus in one pool. Further amplification and sequencing demonstrated the occurrence of Haemoproteus majoris lineage PARUS1 (n = 1) as well as several Plasmodium species and lineages, including Plasmodium relictum SGS1 (n = 16) and GRW11 (n = 1), P. matutinum LINN1 (n = 13), P. vaughani SYAT05 (n = 10), P. circumflexum TURDUS01 (n = 3), P. cathemerium PADOM02 (n = 1) and Plasmodium sp. SYBOR02 (n = 1) and PLOPRI01 (n = 1). The infections were detected in Culex pipiens sensu lato (n = 40), Culiseta morsitans/fumipennis (n = 6) and Aedes cinereus/geminus (n = 1).

Conclusions

Although the overall Plasmodium minimum infection rate (5.2) appears to be low, the results demonstrated not only the ongoing circulation of Plasmodium parasites in the German mosquito population, but also the occurrence of eight distinct Plasmodium lineages, with three of them (PADOM02, SYBOR02, PLOPRI01) being detected in Germany for the first time. This study highlights the importance of conducting mosquito-borne pathogen surveillance studies simultaneously targeting vectors and vertebrate hosts, as certain species may be detected more readily in their vectors than in their vertebrate hosts, and vice versa.

Graphical Abstract
An epigenetic hypothesis for ovarian cancer prevention by oral contraceptive pill use
Authors: Avramenko Anna S. , Flanagan James M.
Published: October 2023

Background

Ovarian cancer is the second most common gynecological cancer type after uterine cancers. In 2020, according to worldwide statistics, there were more than 313,000 new cases of ovarian cancer. Most concerning with ovarian cancer is the poor overall survival, with only 30% of patients surviving for longer than 5 years after diagnosis. The reason for this poor outcome includes late diagnosis due to non-specific symptoms and a lack of any highly effective biomarkers of the early stages of ovarian carcinogenesis. However, it is important to note that some modifiable lifestyle factors can be preventative [pregnancy, breastfeeding and combined oral contraceptives pill (COCP) use].

Results

There is now increasing data reporting the role of epigenetic changes, which are detectable in ovarian cancer tumors, suggesting the possibility that epigenetics may also play a key role in the mechanism of long-term effective prevention of ovarian cancer. To our knowledge, there is a lack of high-quality data on the molecular mechanisms of ovarian cancer prevention, although several hypotheses have been proposed.

Conclusions

This review focusses on the evidence for a proposed novel hypothesis—that COCPs act as a chemoprevention through the impact on the epigenome of the cells of origin of ovarian cancer—fallopian tubes epithelium.
A systematic review of mechanistic models used to study avian influenza virus transmission and control
Authors: Lambert Sébastien , Bauzile Billy , Mugnier Amélie , Durand Benoit , Vergne Timothée , Paul Mathilde C.
Published: October 2023

The global spread of avian influenza A viruses in domestic birds is causing increasing socioeconomic devastation. Various mechanistic models have been developed to better understand avian influenza transmission and evaluate the effectiveness of control measures in mitigating the socioeconomic losses caused by these viruses. However, the results of models of avian influenza transmission and control have not yet been subject to a comprehensive review. Such a review could help inform policy makers and guide future modeling work. To help fill this gap, we conducted a systematic review of the mechanistic models that have been applied to field outbreaks. Our three objectives were to: (1) describe the type of models and their epidemiological context, (2) list estimates of commonly used parameters of low pathogenicity and highly pathogenic avian influenza transmission, and (3) review the characteristics of avian influenza transmission and the efficacy of control strategies according to the mechanistic models. We reviewed a total of 46 articles. Of these, 26 articles estimated parameters by fitting the model to data, one evaluated the effectiveness of control strategies, and 19 did both. Values of the between-individual reproduction number ranged widely: from 2.18 to 86 for highly pathogenic avian influenza viruses, and from 4.7 to 45.9 for low pathogenicity avian influenza viruses, depending on epidemiological settings, virus subtypes and host species. Other parameters, such as the durations of the latent and infectious periods, were often taken from the literature, limiting the models’ potential insights. Concerning control strategies, many models evaluated culling (n = 15), while vaccination received less attention (n = 6). According to the articles reviewed, optimal control strategies varied between virus subtypes and local conditions, and depended on the overall objective of the intervention. For instance, vaccination was optimal when the objective was to limit the overall number of culled flocks. In contrast, pre-emptive culling was preferred for reducing the size and duration of an epidemic. Early implementation consistently improved the overall efficacy of interventions, highlighting the need for effective surveillance and epidemic preparedness.
Unmapped short reads from whole-genome sequencing indicate potential infectious pathogens in German Black Pied cattle
Authors: Neumann Guilherme B. , Korkuć Paula , Reißmann Monika , Wolf Manuel J. , May Katharina , König Sven , Brockmann Gudrun A.
Published: October 2023

When resequencing animal genomes, some short reads cannot be mapped to the reference genome and are usually discarded. In this study, unmapped reads from 302 German Black Pied cattle were analyzed to identify potential pathogenic DNA. These unmapped reads were assembled and blasted against NCBI’s database to identify bacterial and viral sequences. The results provided evidence for the presence of pathogens. We found sequences of Bovine parvovirus 3 and Mycoplasma species. These findings emphasize the information content of unmapped reads for gaining insight into bacterial and viral infections, which is important for veterinarians and epidemiologists.
Relationship between psychological detachment from work and depressive symptoms: indirect role of emotional exhaustion and moderating role of self-compassion
Authors: Wu Qinglu , Qi Tengfei , Wei Jun , Shaw Amy
Published: October 2023

The importance of psychological detachment during nonwork time has been emphasized, and its effect on depressive symptoms has been identified. However, the mechanism underlying this association remains to be elucidated. This study was conducted to identify the indirect role of emotional exhaustion in the association between psychological detachment and depressive symptoms and the moderating role of self-compassion in the relationship between emotional exhaustion and depressive symptoms on the basis of the recovery–engagement–exhaustion model and emotion regulation theory. Through an online survey, relevant data were collected from 727 university teachers (mean age, 37.65 ± 7.77 years; 38.5% men). Indirect and moderation effect were analyzed through structural equation modeling (Mplus). Psychological detachment was found to be associated with depressive symptoms through emotional exhaustion. Self-compassion moderated the association between emotional exhaustion and depressive symptoms. The association between emotional exhaustion and depressive symptoms was weaker among university teachers with high levels of self-compassion than among those with low levels of self-compassion. This study improves our understanding of the association between psychological detachment and depressive symptoms by identifying the emotional pathway and protective function of self-compassion. Interventions for improving mental health in work context should be designed considering psychological detachment and self-compassion to deal with work-induced emotional strain.
The hidden costs of emotional labor on withdrawal behavior: the mediating role of emotional exhaustion, and the moderating effect of mindfulness
Authors: Peng Peng , Li Xintian
Published: October 2023

Background

Employees’ withdrawal behavior concerns organization leaders and policymakers in many countries. However, the specific mechanism which emotional labor affects withdrawal behavior has yet to be thoroughly discussed. There needs to be systematic research on how different emotional labor strategies affect work withdrawal, whether directly or through individual perception, and how to respond.

Methods

A total of 286 hotel and catering service employees participated in our study. A series of hierarchical moderated regression analyses were performed to test the hypothesis.

Results

The results indicated that surface acting positively affected withdrawal behavior, while deep acting had a negative effect. Emotional exhaustion mediated in this relationship of surface acting with withdrawal behavior and deep acting with withdrawal behavior. Mindfulness showed moderation effects between emotional exhaustion and withdrawal behavior.

Conclusions

Emotional labor and emotional exhaustion are significant in predicting employees’ intentions to withdraw, given that emotional exhaustion partially mediates the effects of emotional labor on withdrawal behavior. Significantly, the relationship between emotional exhaustion and withdrawal behavior is weakened by mindfulness.
Trends in massive transfusion practice for trauma in Japan from 2011 to 2020: a nationwide inpatient database study
Authors: Ohbe Hiroyuki , Tagami Takashi , Endo Akira , Miyata Shigeki , Matsui Hiroki , Fushimi Kiyohide , Kushimoto Shigeki , Yasunaga Hideo
Published: October 2023

Background

Previous studies have reported conflicting results regarding fresh frozen plasma (FFP)-to-red blood cell (RBC) ratio and platelet-to-RBC ratio on outcomes for massive transfusion for trauma. Moreover, nationwide data on massive transfusion practices for trauma in the real-world clinical setting are scarce. This study aimed to examine the nationwide practice patterns and trends in massive transfusion for trauma in Japan using a national administrative, inpatient database.

Method

We identified patients who underwent emergency hospitalization for trauma and received massive transfusion, defined as administration of at least 20 units of RBC within the first 2 days of admission, using the nationwide inpatient database, which covers approximately 90% of all tertiary emergency hospitals in Japan, between 2011 and 2020. Trends in the incidence and practice patterns of massive transfusion were described by calendar year. The association of practice patterns with mortality or adverse events was tested.

Results

A total of 3,530,846 trauma hospitalizations were identified, of which 5247 (0.15%) received massive transfusion. A significant declining trend was observed in the incidence of massive transfusion in trauma hospitalizations from 0.24% in 2011 to 0.10% in 2020 (P for trend < 0.001). The FFP-to-RBC ratio rose significantly from 0.77 in 2011 to 1.08 in 2020 (P for trend < 0.001), while the platelet-to-RBC ratio remained virtually unchanged from 0.71 in 2011 to 0.78 in 2020 (P for trend 0.060). Massive transfusion with lower FFP-to-RBC (< 0.75) and platelets-to-RBC ratio (< 1.00) were associated with increased in-hospital mortality compared with those ≥ 1.00, while there were linear increases in adverse events with increasing FFP and platelets ratios.

Conclusions

This study demonstrated a declining trend in the incidence and a rise in higher FFP-to-RBC ratios in massive transfusion in association with patient outcomes for trauma from 2011 to 2020 in Japan.
A review of shallow slow earthquakes along the Nankai Trough
Authors: Takemura Shunsuke , Hamada Yohei , Okuda Hanaya , Okada Yutaro , Okubo Kurama , Akuhara Takeshi , Noda Akemi , Tonegawa Takashi
Published: October 2023

Slow earthquakes occur at deep and shallow plate boundaries along the Nankai Trough. Deep slow earthquakes are continuously distributed along the 30–40 km depth contours of the upper surface of the subducted Philippine Sea Plate. In contrast, shallow slow earthquakes occur in limited regions: Hyuga-nada, off Cape Muroto, and southeast off the Kii Peninsula. This review provides an overview of the up-to-date seismological, geodetic, geological, and experimental results in the shallow Nankai area for a unified understanding of the spot-like occurrence of shallow slow earthquakes. Shallow slow earthquakes tend to be distributed in transitional regions between the frictionally locked and stably sliding zones on the plate boundary. Based on geological and experimental studies, the lithology of incoming sediments and their friction coefficients can be variable along the Nankai Trough. Laboratory friction experiments revealed that sediments under shallow plate boundary conditions often exhibit positive (a − b) values, while negative (a − b) is possible via several processes. Subducted seamounts create complex fracture networks and stress shadows in their surrounding areas; however, not all subducted seamounts are related to shallow slow earthquake activities. This incomplete correlation suggests that alternative factors are required to explain the spot-like distribution of shallow slow earthquakes in the Nankai subduction zone. High pore fluid pressure conditions around shallow slow earthquake zones were interpreted based on seismological structural studies. In addition, ambient noise monitoring revealed temporal changes in seismic velocity structures associated with shallow slow earthquake migrations. This result suggests a close link between pore fluid migration and shallow slow earthquake episodes. Because transient changes in pore fluid pressure can lead to various slip behaviors, the episodic migration of pore fluid around the plate boundary could promote shallow slow earthquake activity along the Nankai Trough.

Graphical Abstract
Elucidating regulatory processes of intense physical activity by multi-omics analysis
Authors: Nakayasu Ernesto S. , Gritsenko Marina A. , Kim Young-Mo , Kyle Jennifer E. , Stratton Kelly G. , Nicora Carrie D. , Munoz Nathalie , Navarro Kathleen M. , Claborne Daniel , Gao Yuqian , Weitz Karl K. , Paurus Vanessa L. , Bloodsworth Kent J. , Allen Kelsey A. , Bramer Lisa M. , Montes Fernando , Clark Kathleen A. , Tietje Grant , Teeguarden Justin , Burnum-Johnson Kristin E.
Published: October 2023

Background

Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.

Methods

To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics modalities.

Results

Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.

Conclusion

This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.
OptiCogs: feasibility of a multicomponent intervention to rehabilitate people with cognitive impairment post-stroke
Authors: O’ Donoghue Mairéad , Boland Pauline , Taylor Sinead , Hennessy Edel , Murphy Eva , Leahy Siobhan , McManus John , Lisiecka Dominika , Purtill Helen , Galvin Rose , Hayes Sara
Published: October 2023

Background

Stroke is a leading cause of death and disability worldwide. Despite the prevalence and associated burden of cognitive impairment post-stroke, there is uncertainty regarding optimal cognitive rehabilitation for people post-stroke. This study aimed to assess whether a multicomponent intervention, called OptiCogs, is feasible, acceptable, and safe for people with cognitive impairment post-stroke. A secondary aim was to explore changes in cognitive function, fatigue, quality of life, physical function, and occupational performance, from pre-intervention to post-intervention.

Methods

A feasibility study was conducted where people post-stroke with cognitive impairment enrolled in a 6-week multicomponent intervention. The primary outcomes recorded included response rate, recruitment rate, retention rate, adherence to the intervention protocol, adverse events, and acceptability of the intervention to people post-stroke. Secondary outcomes included (i) change in cognitive functioning using the Addenbrooke’s Cognitive Examination III, (ii) fatigue using the Fatigue Severity scale, (iii) quality of life using the Stroke Specific Quality of Life scale (iv) physical function using the patient-reported outcomes measurement information system, and (v) patient-reported occupational performance using the Canadian Occupational Performance Measure. The Consolidated Standards of Reporting Trials extension reporting guidelines were followed, for pilot and feasibility studies, to standardize the conduct and reporting of this study.

Results

The response rate was 10.9%. Nine eligible participants were enrolled during the 4-month recruitment period, with eight participants completing the entire 6-week intervention, as well as the pre- and post-intervention outcome measures. There were no reported adverse events. Participants were satisfied with the intervention and found it acceptable overall. Results of the secondary outcomes were promising for cognitive function (ACE III, pre: 63.3 ± 23.9 to post: 69 ± 24.6), fatigue (FSS, pre: 52.5 ± 7.3 to post: 45.6 ± 7.2), quality of life (SSQoL, pre: 131.0 ± 26.3 to post: 169.9 ± 15.3), physical function (PROMIS-PF, pre: 15.5 ± 6.3 to post: 15.8 ± 5.3), and occupational performance (COPM performance, pre: 9.3 ± 2.3 to post: 22.9 ± 4.2) and COPM satisfaction, pre: 9.9 ± 2.1 to post: 22.7 ± 3.5).

Conclusion

Preliminary results suggest low-modest recruitment and high retention rates for the OptiCogs intervention. Changes in cognitive function, fatigue, quality of life, and self-reported occupational performance show improvement from pre- to post-intervention. These potential benefits require further testing in a larger pilot trial.

Trial registration

NCT05414539.
Shifts in energy allocation and reproduction in response to temperature in a small precocial mammal
Authors: Trillmich Fritz , Guenther Anja
Published: October 2023

Background

Species adjust to changes in temperature and the accompanying reduction in resource availability during the annual cycle by shifts in energy allocation. As it gets colder, the priority of energy allocation to maintenance increases and reproduction is reduced or abandoned.

Results

We studied whether and how young female guinea pigs (Cavia porcellus) adjust even under ad libitum food conditions growth, storage of fat reserves and reproduction when kept at 5 °C versus 15 °C, and how offspring born into these conditions compensate during development to independence. Reproducing females grew less in the cold. Their lower weight resulted largely from less fat storage whereas growth in fat free mass was about the same for both groups. The increased need for thermoregulation diminished fat storage most likely due to the development of more brown fat tissue. Reproductive activity did not differ between groups in terms of litter frequency, mass and size. However, females in 5 °C weaned pups later (around day 25) than females in 15 °C (around day 21). Later weaning did not make up for the higher energy expenditure of pups in cold conditions leading to slower growth and less fat storage. Female pups born into the cold matured later than those born in 15 °C. Investment in reproduction continued but allocation to individual pups declined.

Conclusions

In more thermally demanding conditions female guinea pigs - even under ad libitum food abundance - transfer the higher costs of maintenance and reproduction largely to offspring.
Acute phase reactants in non-COVID-19 community-acquired pneumonia
Authors: Akl Yosri , Elkomy Ahmed , Ibrahim Eman Kamal
Published: October 2023

Background

Acute phase reactants (APR) are markers of inflammation that could be applied for the assessment of community-acquired pneumonia (CAP) severity in association with various pneumonia severity scores. So, the aim of the study was to assess levels of APR such as total leucocytic count (TLC), platelets, neutrophils, neutrophils-to-lymphocyte ratio (NLR), CRP, D-dimer, ferritin, and ESR in patients with CAP and to correlate between their values and disease severity.

Methodology

The study included 51 patients diagnosed as non-COVID-19 (CAP). Patients were classified into two groups group A (pneumonia only) and group B (pneumonia complicated with empyema/complicated para-pneumonic effusion). All patients underwent clinical evaluation, CURB65, radiological assessment, and blood sampling to measure APR.

Results

The mean age of patients was 47 ± 17 years. The main symptoms were productive cough (90.2%) and Fever (92.2%).TLC, platelets, neutrophils, CRP, D-dimer, ferritin, and ESR were elevated than normal values. Significant positive correlations were found between the duration of fever and CRP, D-dimer, and ferritin with p values = 0.024, 0.012, and 0.034 respectively. Significant positive correlations were found between CURB65 and both CRP and ferritin with p values = 0.007 and 0.020. A significant increase in platelet count and ESR values was found in group B than in group A.

Conclusion

APR are important markers that can be used in the assessment of CAP in collaboration with clinical evaluation and severity scores. CRP, D-dimer, and ferritin were positively correlated with CURB65, while ESR and platelets could be considered predictors of the development of complications.

Trial registration

Retrospectively registered, registration number NCT05926089, date of registration is 06/29/2023.
Adverse childhood experiences and psychological functioning among women with schizophrenia or bipolar disorder: population-based study
Authors: Köhler-Forsberg Ole , Ge Fenfen , Hauksdóttir Arna , Thordardottir Edda Bjork , Ásbjörnsdóttir Kristjana , Rúnarsdóttir Harpa , Tómasson Gunnar , Jakobsdóttir Jóhanna , Guðmundsdóttir Berglind , Björnsson Andri Steinþór , Sigurðsson Engilbert , Aspelund Thor , Valdimarsdottir Unnur A.
Published: October 2023

Background

Adverse childhood experiences (ACEs) are well-known risk factors for schizophrenia and bipolar disorder.

Aims

The aim was to study the associations between specific ACEs and psychological functioning in women with schizophrenia or bipolar disorder.

Method

Among 29 367 women (mean age 44 years) from the Icelandic Stress-And-Gene-Analysis (SAGA) study, 534 (1.8%, mean age 40) reported having been diagnosed with schizophrenia or bipolar disorder, which were combined to ‘severe mental disorders’. Participants reported on 13 types of ACEs, childhood deprivation and psychological functioning (defined as coping ability and current symptoms of depression, anxiety and sleep disturbances). Adjusted Poisson regression calculated prevalence ratios (PRs) between ACEs and severe mental disorders. Linear regression assessed the association between ACEs and psychological functioning among women with a severe mental disorder.

Results

Women with a severe mental disorder reported more ACEs (mean 4.57, s.d. = 2.82) than women without (mean 2.51, s.d. = 2.34) in a dose-dependent manner (fully-adjusted PR = 1.23 per ACE, 95% CI 1.20–1.27). After mutual adjustment for other ACEs, emotional abuse, sexual abuse, mental illness of a household member, emotional neglect, bullying and collective violence were associated with severe mental disorders. Among women with severe mental disorders, a higher number of ACEs was associated with increased symptom burden of depression (β = 2.79, 95% CI = 1.19–4.38) and anxiety (β = 2.04, 95% CI = 0.99–3.09) including poorer sleep quality (β = 0.83, 95% CI = 0.07–1.59). Findings were similar for schizophrenia and bipolar disorder separately.

Conclusion

Women with schizophrenia or bipolar disorder show a strong history of ACEs, which may interfere with their psychological functioning and, therefore, need to be addressed as part of their treatment, for example, with trauma-focused psychotherapy.
Exploring the complex relationships between coping strategies, locus of control and self-esteem with psychopathology: structural equation modeling with a special focus on clinical high-risk of psychosis
Authors: Rinaldi Giulia , Osman Naweed , Kaess Michael , Schimmelmann Benno G. , Kindler Jochen , Schultze-Lutter Frauke , Michel Chantal
Published: October 2023

Background

Coping strategies, competence, and locus of control (LOC) beliefs are important predictors of mental health (MH). However, research into their complex interactions has produced mixed results. Our study investigated them further in the previously unexplored context of clinical high-risk (CHR) of psychosis.

Methods

We tested six alternative structural equation models in a community sample (N = 523), hypothesizing a mediating role of coping and treating CHR symptoms as (i) an additional mediator or (ii) a specific outcome. Our measurement model included two latent factors of MH: (1) psychopathology (PP), consisting of presence of mental disorders, global and psychosocial functioning, and (2) self-rated health (SRH) status.

Results

In the model with the best Akaike Information Criterion and the latent factors as outcome variables, maladaptive coping completely mediated the impact of maladaptive LOC on PP and SRH. Additionally, CHR symptoms partially mediated the effect of maladaptive coping on PP and SRH in the community sample, as long as sex was not entered into the model. In the clinical sample (N = 371), the model did not support a mediation by CHR symptoms, despite significant pathways with both coping and MH outcomes; further, competence beliefs directly impacted SRH.

Conclusions

Coping strategies are an important intervention target for MH promotion, especially in the community. In clinical populations, interventions focusing on coping strategies may improve CHR symptoms, thus potentially supporting better MH, especially SRH. Additionally, due to their mostly cascading effects on MH, improving competence and LOC beliefs may also promote psychological well-being.
Measuring What Is Meaningful in Cancer Cachexia Clinical Trials: A Path Forward With Digital Measures of Real-World Physical Behavior
Authors: Aryal Suvekshya , Bachman Shelby L. , Lyden Kate , Clay Ieuan
Published: October 2023

PURPOSE

The burden of cancer cachexia on patients' health-related quality of life, specifically their physical functioning, is well documented, but clinical trials thus far have failed to show meaningful improvement in physical functioning. The purpose of this review is to summarize existing methods of assessing physical function in cancer cachexia, outline a path forward for measuring what is meaningful to patients using digital measures derived from digital health technologies (DHTs), and discuss the current landscape of digital measures from the clinical and regulatory standpoint.

DESIGN

For this narrative review, peer-reviewed articles were searched on PubMed, clinical trials records were searched on clinicaltrials.gov, and records of digital measures submitted for regulatory qualification were searched on the US Food and Drug Administration's Drug Development Tool Qualification Program database.

RESULTS

There are gaps in assessing aspects of physical function that matter to patients. Existing assessment methods such as patient-reported outcomes and objective performance outcomes have limitations, including their episodic nature and burden to patients. DHTs such as wearable sensors can capture real-world physical behavior continuously, passively, and remotely, and may provide a more comprehensive picture of patients' everyday functioning. Recent regulatory submissions showcase potential clinical implementation of digital measures in various therapeutic areas.

CONCLUSION

Digital measures of real-world physical behavior present an opportunity to detect and demonstrate improvements in physical functioning in cancer cachexia, but evidence-based development is critical. For their use in clinical and regulatory decision making, studies demonstrating meaningfulness to patients as well as feasibility and validation are necessary.
Multicancer Early Detection Tests: An Overview of Early Results From Prospective Clinical Studies and Opportunities for Oncologists
Authors: Post Carl , Braun Theodore P. , Etzioni Ruth , Nabavizadeh Nima
Published: October 2023

A multitude of blood-based multicancer early detection (MCED) tests assessing cancer-related alterations in circulating genomic analytes and other associated signatures are currently being developed with the potential to disrupt current single-organ screening paradigms. Pathways for clinical implementation of these novel MCED tests have not been delineated, particularly for the patients with signal positive results requiring additional confirmatory testing. In this overview, we highlight early results from prospective clinical studies testing the efficacy of genomic MCED tests in cohorts of patients without known cancer diagnoses. Additionally, we discuss a proposed professional expansion of the oncology practice relating to the diagnostic workup of individuals found to have an MCED signal positive for cancer. As MCED blood tests have the potential to dramatically upend current cancer screening paradigms and downstream cancer therapy, it is imperative for oncologists to be aware of important clinical studies and the multitude of unanswered questions. The current gaps in the clinical implication of these tests may serve as a meaningful and rewarding expansion of oncology practice.