bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from CD49a Targeting Enhances NK Cell Function and Antitumor Immunity
Authors: Zhang Yu , Li Yangyang , Zhang Zhengfeng , Zheng Xiaodong , Peng Hui , Tian Zhigang , Sun Rui , Sun Haoyu
Published: January 2025

Abstract
Approximately 70% of patients receiving immune checkpoint blockade therapies develop treatment resistance. Thus, there is a need for the identification of additional immunotherapeutic targets. CD49a is a membrane protein expressed on NK cells and T cells. In this study, we found that CD49a was highly expressed on the surface of tumor-infiltrating NK cells in various mouse tumor models and that CD49a+ tumor-infiltrating NK cells were more exhausted than CD49a− tumor-infiltrating NK cells. Furthermore, CD49a or NK-specific CD49a deficiency slowed tumor growth and prolonged survival in several mouse tumor models, primarily through the essential role played by NK cells in antitumor activities. Blockade of CD49a using an mAb suppressed tumor development in mice, and combination treatment with anti–PD-L1 further enhanced antitumor efficacy. Our research reveals CD49a on NK cells as an immunotherapeutic target and highlights the potential clinical applications of CD49a-targeted therapies.
Data from Preclinical Development of T Cells Engineered to Express a T-Cell Antigen Coupler Targeting Claudin 18.2–Positive Solid Tumors
Authors: Xu Stacey X. , Wang Ling , Ip Philbert , Randhawa Ritu R. , Benatar Tania , Prosser Suzanna L. , Lal Prabha , Khan Alima Naim , Nitya-Nootan Thanyashanthi , Thakor Gargi , MacGregor Heather , Hayes Danielle L , Vucicevic Andrea , Mathew Princy , Sengupta Sadhak , Helsen Christopher W. , Bader Andreas G.
Published: January 2025

Abstract
The T-cell antigen coupler (TAC) is a chimeric receptor that facilitates tumor antigen–specific activation of T cells by co-opting the endogenous T-cell receptor complex in the absence of tonic signaling. Previous data demonstrate that the TAC affords T cells with the ability to induce durable and safe antitumor responses in preclinical models of hematologic and solid tumors. In this study, we describe the preclinical pharmacology and safety of an autologous Claudin 18.2 (CLDN18.2)-directed TAC T-cell therapy, TAC01-CLDN18.2, in preparation for a phase I/II clinical study in subjects with CLDN18.2-positive solid tumors. Following a screen of putative TAC constructs, the specificity, activity, and cytotoxicity of TAC T cells expressing the final CLDN18.2-TAC receptor were evaluated in vitro and in vivo using gastric, gastroesophageal, and pancreatic tumor models as well as human cells derived from normal tissues. CLDN18.2-specific activity and cytotoxicity of CLDN18.2-TAC T cells were observed in coculture with various 2D tumor cultures naturally expressing CLDN18.2 as well as tumor spheroids. These effects occurred in models with low antigen levels and were positively associated with increasing CLDN18.2 expression. CLDN18.2-TAC T cells effectively eradicated established tumor xenografts in mice in the absence of observed off-target or on-target/off-tumor effects, elicited durable efficacy in recursive killing and tumor rechallenge experiments, and remained unreactive in coculture with human cells representing vital organs. Thus, the data demonstrate that CLDN18.2-TAC T cells can induce a specific and long-lasting antitumor response in various CLDN18.2-positive solid tumor models without notable TAC-dependent toxicities, supporting the clinical development of TAC01-CLDN18.2.
Host tissue factors predict immune surveillance and therapeutic outcomes in gastric cancer
Authors: Abate Miseker , Stroobant Emily , Fei Teng , Lin Ya-Hui , Shimada Shoji , Drebin Harrison , Chen Eunise , Tang Laura H. , Shah Sohrab P. , Wolchok Jedd D. , Janjigian Yelena Y. , Strong Vivian E. , Vardhana Santosha A.
Published: January 2025

The immune composition of solid tumors is typically inferred from biomarkers, such as histologic and molecular classifications, somatic mutational burden, and PD-L1 expression. However, the extent to which these biomarkers predict the immune landscape in gastric adenocarcinoma—an aggressive cancer often linked to chronic inflammation—remains poorly understood. We leveraged high-dimensional spectral cytometry to generate a comprehensive single-cell immune landscape of tumors, normal tissue, and lymph nodes from patients in the Western Hemisphere with gastric adenocarcinoma. The immune composition of gastric tumors could not be predicted by traditional metrics such as tumor histology, molecular classification, mutational burden, or PD-L1 expression via IHC. Instead, our findings revealed that innate immune surveillance within tumors could be anticipated by the immune profile of the normal gastric mucosa. Additionally, distinct T-cell states in the lymph nodes were linked to the accumulation of activated and memory-like CD8+ tumor-infiltrating lymphocytes (TILs). Unbiased re-classification of patients based on tumor-specific immune infiltrate generated four distinct subtypes with varying immune compositions. Tumors with a T-cell-dominant immune subtype, which spanned TCGA molecular subtypes, were exclusively associated with superior responses to immunotherapy. Parallel analysis of metastatic gastric cancer patients treated with immune checkpoint blockade showed that patients who responded to immunotherapy had a pre-treatment tumor composition that corresponded to a T-cell-dominant immune subtype from our analysis. Taken together, this work identifies key host-specific factors associated with intratumoral immune composition in gastric cancer and offers an immunological classification system that can effectively identify patients likely to benefit from immune-based therapies.
Supplemental Figure 2 from Clonal Hematopoiesis of Indeterminate Potential and its Association with Treatment Outcomes and Adverse Events in Patients with Solid Tumors
Authors: Krishnan Tharani , Solar Vasconcelos Joao Paulo , Titmuss Emma , Vanner Robert J. , Schaeffer David F. , Karsan Aly , Lim Howard , Ho Cheryl , Gill Sharlene , Yip Stephen , Chia Stephen K. , Kennecke Hagen F. , Jonker Derek J. , Chen Eric X. , Renouf Daniel J. , O’Callaghan Chris J. , Loree Jonathan M.
Published: January 2025

Progression free survival for patients on PREDiCT-l, split by tumor type. Therapy received is indicated in each title above each Kaplan Meier curve.
Echocardiography of turquoise-fronted parrots (Amazona aestiva, Linnaeus, 1758) subjected to physical orpharmacological restraint protocols
Authors: Kuster Marieta Cristina Couto , Santos Amanda Maria Miranda Rodrigues dos , Pontes Beathriz Giostri , Spalenza Thiago Barbosa , Resende Gabriela de Oliveira , Oliveira Paula da Rocha , Trivilin Leonardo Oliveira
Published: January 2025

The tranquilizers can influence the preload and the afterload and alter echocardiographic parameters in parrots since echocardiography in these animals invariably depends on pharmacological containment. This study aimed to determine the echocardiographic parameters of turquoise-fronted parrots (Amazona aestiva) under physical and pharmacological restraint using midazolam and a combination of midazolam and ketamine and evaluate these drugs as facilitators of echocardiography. Echocardiographic examinations were performed on 10 healthy parrots using three restraint protocols at 30-day washout: midazolam 1.5 mg/kg IM (PM protocol), midazolam 0.2 mg/kg with ketamine 25 mg/kg IM (PMK protocol), and physical (PRP protocol). Apical images were obtained using the horizontal ventromedian approach using B-mode. Sedation scores and duration of exams were determined. In the PMK protocol, it was observed that Vmax-Ao (p = 0.0052), Ao-Grad (p = 0.0110), LVLd (p = 0.0219), LALd (p = 0.0304), IVSs (p = 0.0219) and IVSd (p = 0.0156) was lower than the PRP protocol and equal to PM protocol. However, cardiac debit was lower than the PM protocol (p = 0.0417) and equal to the PRP protocol. The A-wave velocity was greater than the E-wave velocity in 80% of the birds, while 20% showed E-wave velocity greater than the A wave velocity in the PMK and PM protocols. PMK protocol showed a higher level of sedation without resistance to manipulation. In parrots, ketamine and midazolam alter echocardiographic parameters dependent on preload and afterload, but midazolam causes minor changes. In addition, pharmacological restraint facilitates echocardiography without altering the examination time.
Rose Marie Muraro: catolicismo, feminismo, edição e censura
Authors: Reimão Sandra , Nery João Elias , Maués Flamarion
Published: January 2025

Este artigo enfoca a censura, pelo Ministério da Justiça, dos livros de Rose Marie Muraro A mulher na construção do mundo futuro (primeira edição 1966) e A automação e o futuro do homem (1968). Buscamos compreender os vetos censórios em 1975, muitos anos depois do lançamento e quando já tinham tido ampla discussão entre o público. A censura desses livros, a nosso ver, tem que ser analisada como uma tentativa de coação e demonstração de poder do governo ditatorial que estava sentindo a pressão das crescentes mobilizações feministas e pela democracia. Este artigo articula-se em duas partes: 1) Panorama das atividades de Rose Marie Muraro, com destaque para sua atuação na Editora Vozes; 2) Abordagem das temáticas das duas obras, e análise contextualizada sobre o despacho de veto censório.
Painting Humanitarian Experiences at Sea: The Raft of the Medusa
Authors: Martín-Moruno Dolores
Published: January 2025

Taking We’re Not All in the Same Boat (2015) – Banksy’s reinterpretation of Théodore Géricault’s The Raft of the Medusa (1819) – as its departure point, this article explores the maritime routes through which artists have produced and circulated humanitarian experiences amongst international audiences as a colourful palette of embodied practices, emotions, sensations, feelings, perceptions and thoughts. Drawing on the accounts of the Medusa’s survivors, I analyse the advocacy strategies used by Géricault in his painting to make the spectator feel the sufferings experienced by the shipwrecked aboard the raft through the hallucinations provoked by calenture: a madness which affected sailors who crossed the tropics. Ultimately, a comparison between Géricault’s and Banksy’s artworks allows us to sail on a raft – the humanitarian theatre par excellence at sea – to connect past and present-day migratory journeys through the legacies of colonialism and denounce Western immigration controls by performing solidarity towards refugees.
Automated quantification of anterior chamber cells using swept-source anterior segment optical coherence tomography
Authors: Pillar Shani , Kadomoto Shin , Chen Keren , Gonzalez Saitiel Sandoval , Cherian Nina , Privratsky Joseph K. , Zargari Nicolette , Jackson Nicholas J. , Corradetti Giulia , Chen Judy L. , Sadda SriniVas R. , Holland Gary N. , Tsui Edmund
Published: January 2025

Purpose

To validate automated counts of presumed anterior chamber (AC) cells in eyes with histories of uveitis involving the anterior segment using swept-source (SS) anterior segment optical coherence tomography (AS-OCT) against manual counts and compare automated counts against Standardized Uveitis Nomenclature (SUN) criteria.

Methods

Eyes were imaged with the ANTERION SS AS-OCT device (Heidelberg Engineering). A fully automated custom algorithm quantified the number of hyper-reflective foci (HRF) in line-scan images. Automated and manual counts were compared using interclass correlation (ICC) and Pearson correlation coefficient. Automated counts were compared to SUN grades using a mixed-effects linear regression model.

Results

90 eyes (54 participants) were included; 67 eyes (41 participants) had histories of uveitis, while 23 eyes (13 healthy participants) served as controls. ICC comparing automated to manual counts was 0.99 and the Pearson correlation coefficient was 0.98. Eyes at each SUN grade with corresponding median HRF (interquartile range [IQR]) were: Grade 0, 42 eyes, 2 HRF (0,4); 0.5+, 10 eyes, 10 HRF (8,15); 1+, 9 eyes, 22 HRF (15,33); 2+, 3 eyes, 27 HRF; 3+, 2 eyes, 128 HRF; 4+, 1 eye, 474 HRF. For every 1-step increase in grade, automated count increased by 38 (p < 0.001) or 293% (Pearson correlation coefficient 0.80, p < 0.001). Automated counts differed significantly between clinically inactive eyes (2 HRF [0,4]) and controls (0 HRF [0,1], p = 0.02).

Conclusions

Our algorithm accurately counts HRF when compared to manual counts, with strong correlation to SUN clinical grades. SS AS-OCT offers the advantage of imaging of the entire AC and may allow detection of subclinical inflammation in eyes that appear clinically inactive.
Measuring fluid balance in end-stage renal disease with a wearable bioimpedance sensor
Authors: Bremnes Frida , Øien Cecilia Montgomery , Kvaerness Jørn , Jaatun Ellen Andreassen , Aas Sigve Nyvik , Saether Terje , Lund Henrik , Romundstad Solfrid
Published: January 2025

Background

Accurate assessment of fluid volume and hydration status is essential in many disease states, including patients with chronic kidney disease. The aim of this study was to investigate the ability of a wearable continuous bioimpedance sensor to detect changes in fluid volume in patients undergoing regular hemodialysis (HD).

Methods

31 patients with end-stage renal disease were enrolled and monitored with a sensor patch (Re:Balans®) on the upper back through two consecutive HD sessions and the interdialytic period between. The extracellular resistance RE was calculated from multi-frequency bioimpedance measurements and was hypothesized to correlate with the amount of extracted fluid during dialysis.

Results

Only HD sessions with a positive net fluid extraction were included in the primary analysis. Participants had an increase of 7.5 ± 4.3 Ω (Ohm) in RE during the first HD and 6.2 ± 2.3 Ω during the second HD, and a fluid extraction (ultrafiltration (UF) volume) of 1.5 ± 0.8 L and 1.2 ± 0.6 L, respectively. The relative change in RE during HD correlated strongly with UF volume (r = 0.82, p < 0.001). During the interdialytic period, the patients had a mean decrease in RE of 6.0 ± 3.5 Ω. Longitudinal changes in RE (%) and body weight (kg) over the entire study period was negatively correlated (r = -0.61 p < 0.001). Longitudinal changes in blood samples and cardiovascular changes were also in agreement with changes in weight and RE.

Conclusions

The results of this clinical investigation indicate that the investigational device is capable of tracking both rapid and gradual changes in hydration status in patients undergoing regular HD.
COVID-19 workplace countermeasures that occupational physicians could not change in Japan: a qualitative study
Authors: Igarashi Yu , Tateishi Seiichiro , Matsuoka Juri , Sawajima Tomoko , Kawasumi Mika , Harada Arisa , Mori Koji
Published: January 2025

Background

During the COVID-19 pandemic, information and circumstances changed from moment to moment, including the accumulation of scientific knowledge, the emergence of variants, social tolerance, and government policy. Therefore, it was important to adapt workplace countermeasures punctually and flexibly based on scientific evidence and according to circumstances. However, there has been no assessment of changes in workplace countermeasures. With a view toward preparedness for future pandemics, we surveyed COVID-19 workplace countermeasures that occupational physicians considered as needing to be changed but went unchanged.

Methods

We invited 685 professional occupational physicians certified by Japan Society for Occupational Health to complete an online questionnaire by sending postcards with QR codes. The main questions concerned countermeasures that the participants wanted to change but could not. The survey period was from February 21 to April 28, 2022. The responses were analyzed using the KJ method.

Results

Of the 168 invitees (24.5%) who responded to the survey, 125 reported countermeasures that needed to be changed (total count: 254). The responses were categorized into basic systems, occupational health services, workplace countermeasures, vaccines, and incidents, with a code count of 7, 8,147, 10, and 82, respectively. The type of countermeasure was 115 for countermeasures to be strengthened (CBS), 110 for measures to be mitigated (CBM), and 29 for neither.

Conclusions

Often-mentioned CBS were increased teleworking, strengthened ventilation, smoking cessation, and promotion of vaccines. Often-mentioned CBM were relaxation of protective equipment rules, discontinued environmental disinfection, and shorted isolation and reinstatement. In the early pandemic phases, CBSs were frequently mentioned, whereas CBMs were featured more prominently in the latter phases. The survey revealed countermeasures that occupational physicians thought needed to be changed but were not changed in practice. For future responses to emerging and reemerging infectious diseases, it will be necessary to establish rules compatible with flexible modification of workplace countermeasures in response to changing circumstances.
Changes to muscle and fascia tissue after eighteen days of ankle immobilization post-ankle sprain injury: an MRI case study
Authors: Perera Meeghage Randika , Su Pan , Holdsworth Samantha , Handsfield Geoffrey
Published: January 2025

Background

Ankle sprains often result in muscle atrophy and reduced range of motion, which can cause long-term ankle instabilities. Understanding the changes to muscle—such as atrophy—and concomitant changes to deep fascia—which may thicken alongside muscle loss—after ankle sprain injury is important to understanding structural changes about the joint and how they might contribute to longer-term impairments. Here, we employ advanced MRI to investigate skeletal muscle and fascial structural changes during the recovery period of one patient undergoing immobilization after ankle sprains.

Material and methods

In this case study, a participant who suffered an ankle sprain underwent initial MRI scans and, after 21 days (18 of which included immobilization), a follow-up MRI. Techniques used included proton density, 3D stack of spirals, and diffusion tensor imaging to analyse muscle and fascia changes pre- and post-injury.

Results

Results showed muscle atrophy in most shank muscles, with volume loss ranging from no change in the lateral gastrocnemius to 12.11% in the popliteus. Thigh muscles displayed hypertrophy of 6% in the hamstrings, while the quadriceps atrophied by 2.5%. Additionally, fascia thickness increased from 0.94 mm to 1.03 mm. Diffusion tensor imaging indicated that the biceps femoris experienced the most significant changes in physiological cross-sectional area, while the rectus femoris showed minimal change.

Conclusion

The findings highlight the variable responses of muscles and a notable thickening of deep fascia post-injury, underscoring its role in recovery from ankle sprains.
Enhanced recovery after surgery protocol optimizes results and cost of laparoscopic radical nephroureterectomy
Authors: Shi Jiageng , Chen Siming , Nie Jiawei , Xiong Kangping , Wang Gang , Qian Kaiyu , Zheng Hang , Wang Xinghuan
Published: January 2025

Purpose

To evaluate the efficacy of an enhanced recovery after surgery (ERAS) strategy for upper tract urothelial carcinoma (UTUC) patients undergoing laparoscopic radical nephroureterectomy (LRNU).

Methods

90 patients who received LRNU at Zhongnan Hospital of Wuhan University between January 2018 and July 2022 were retrospectively analyzed, including 43 in the ERAS group and 47 in the pre-ERAS group. The clinical features, postoperative complications, length of hospital stay (LOS), and hospital expenditures of the two groups were compared via t-test, Mann-Whitney test, and Chi-square test.

Results

In comparison to the pre-ERAS group, the total and postoperative LOS were significantly shorter in the ERAS group [total LOS: 15.0 (13.0–20.0) vs. 21.0 (16.0–26.0), p < 0.001; postoperative LOS: 8.0 (7.0–9.0) vs. 11.0 (9.0–13.0), p < 0.001]. The ERAS group had lower hospitalization costs than that in the pre-ERAS group [56896.40 (48324.30-67498.01) vs. 64249.83 (55574.36-81581.82), p = 0.010]. Additionally, the ERAS group experienced a reduction in postoperative fever incidence (23.4% vs. 4.7%, p = 0.011).

Conclusions

In the realm of LRNU, ERAS protocols are safe and practical for minimizing the LOS while accelerating the rehabilitation of patients undergoing LRNU. This study offers insights for enhancing ERAS protocols for UTUC patients even further.
Healing potentiality of blood clot, S-PRF and A-PRF as scaffold in treatment of non-vital mature single rooted teeth with chronic peri-apical periodontitis following regenerative endodontic therapy: randomized clinical trial
Authors: Darwish Omnia Badawy , Aziz Said Mohamed Abdel , Sadek Hany Samy
Published: January 2025

Objectives

This randomized prospective controlled trial investigated the effectiveness of different strategies of regenerative endodontic therapy on necrotic mature anterior teeth with chronic periapical periodontitis with 18 months follow up.

Methods

A total analyzed 51 adult participant with mature single rooted teeth having necrotic pulp with chronic periapical periodontitis (PAI ≥ 3) were selected. Patients had been randomly categorized into three distinct groups (n = 17 each group). All groups received the same treatment on the first visit. After 2 weeks, regenerative treatment was performed using either blood clot technique, Standard-PRF and Advanced-PRF approach. A standardized radiograph was taken, and the patients instructed for 6, 12 and 18 months follow up periods. Fisher's exact test was applied to compare the frequency of PAI scores at different follow-up intervals between the three groups.

Results

The results showed radiographic success at 18 months (58.8% in blood group, 94.1% in S-PRF group and 76.5% in A-PRF group). There was no statistically significant difference between the three groups according to incidence of healing at 6, 12 and 18 months. Clinical success was 82.4% in blood group and 88.2% in both S-PRF and A-PRF groups. There was no significant difference between the three groups (p = 1). The overall success (clinical and radigraphic) was 76.5%. Incidence of the gaining sensitivity after 12 and 18 months was 29.4% with A-PRF group and 41.2% within the S-PRF group, 17.6% with BC group.

Conclusion

PRF based regenerative technique may outperform the blood clot technique in treatment of non-vital mature teeth with chronic periapical periodontitis. There is a need for future randomized clinical studies to consolidate procedures in this field with more prolonged evaluation periods.

Clinical trial registration

The study was retrospectively registered with ClinicalTrials.gov (ID: NCT04606719) in 28/10/2020.
The influence of sintering of osteoporotic vertebral fractures on the sagittal lumbar profile and degenerative changes
Authors: Beyersdorf Christoph , Prost Max , Röckner Melanie Elisabeth , Maus Uwe Martin , Jacobs Cornelius , Scheyerer Max Joseph
Published: January 2025

Background

Osteoporosis, a skeletal disorder affecting nearly 20% of the global population, poses a significant health concern, with osteoporotic vertebral body fractures (VBF) representing a common clinical manifestation. The impact of osteoporotic sintering fractures in the thoracolumbar spine on the sagittal lumbar profile is incompletely understood and may lead to the onset of clinical symptoms in previously asymptomatic patients.

Methods

This retrospective single-center study analyzed data from patients presenting with osteoporotic spine fractures between 2017 and 2022. Patient selection involved stringent inclusion and exclusion criteria, focusing on radiologically documented osteoporotic sintering fractures in the thoracolumbar junction (TH11-L2). Clinical parameters were recorded and analyzed, alongside lateral-view radiographic assessments utilizing the IDS 7-PACS®-System (Sectra, Linköping, Sweden). Measurements included total lumbar lordosis, lordosis caudal to the fracture, kyphosis of the fractured vertebra, and sacral slope. Statistical analysis was conducted using SPSS 27 (IBM, Armonk, USA).

Results

Thirty patients (73.3% female, 26.7% male) met the inclusion criteria, with an average age of 82.4 years. Analysis revealed a significant increase in kyphosis of the fractured vertebra in the thoracolumbar spine (p < 0.0001) following further sintering of osteoporotic VBF with increased lordosis caudal to the fracture (p < 0.0001). Total lumbar lordosis remained unchanged, alongside sacral slope measurements (p = 0.612 and p = 0.863, respectively).

Conclusion

Progressive sintering of osteoporotic fractures in the thoracolumbar junction accentuates lordosis in underlying segments, potentially exacerbating degenerative changes and symptomatic manifestations. Thus, prioritizing interventions aimed at preventing progressive sintering and restoring sagittal balance is paramount in optimizing treatment outcomes for affected individuals.
Quality of life in people with syndromic heritable thoracic aortic disease and their relatives: a qualitative interview based study
Authors: Velvin Gry , Johansen Heidi , Aune Gunnbjørg , Fugl-Meyer Kerstin , Geirdal Amy Østertun
Published: January 2025

Introduction

The purpose of this study was to investigate perceptions and opinions on what constitutes determinants for quality of life (QoL) in individuals with syndromic Heritable Aortic Disease (sHTAD), utilizing a qualitative study approach. Further to discuss clinical implications and direction for research.

Method

A qualitative focus group interview study was conducted of 47 adults (Marfan syndrome (MFS) = 14, Loeys-Dietz syndrome (LDS) = 11, vascular Ehlers Danlos syndrome (EDS) = 11, relatives = 11). The interviews were digitally recorded and transcribed verbatim. Significant themes were identified, extracted, and organised undergoing content analyses.

Results

The two main themes and 10 subthemes identified; I. Psychosocial well-being; (i) Social engagement and activity, (ii) Self-sufficient in daily living, (iii) Participation in education and work life, (iv) Coping with fear related to the disease, (v) Being able to control and accept fatigue and pain, (vi) Maintaining active engagement with family and friends (vii) Finding health-promoting physical activities. II. Monitoring and meetings with the health service: (viii) Feeling safe and receiving coordinated care, (ix) Being recognized, seen, and accepted, (x) Receiving factual and sober information and advice. The sub-themes seemed mutually interrelated in terms of barriers, strategies, and facilitators for improving quality of life. There was high degree of consensus regarding the factors emphasized as important for QoL among the various diagnostic groups and the relatives.

Conclusion

Based on our findings, to improve QoL in patients with sHTAD we should more effectively integrate the patient`s perspectives and voice on the elements crucial to QoL. In addition, it is vital for developing and customizing validated questionnaires to accurately reflect the factors deemed significant by this specific patient cohort. The research is limited on patients’ perspectives on QoL, and more research is warranted. This might also be crucial for identifying relevant validated QoL instruments that reflect the patients` perceptions of what is vital for QoL.
Phenotypic diversity of CTCs and tdEVs in liquid biopsies of tumour-draining veins is linked to poor prognosis in colorectal cancer
Authors: Cieslik Stefan A. , Zafra Andrés G. , Driemel Christiane , Sudarsanam Monica , Cieslik Jan-Philipp , Flügen Georg , Dizdar Levent , Krieg Andreas , Vaghiri Sascha , Ashmawy Hany , Fung Stephen , Wilms Miriam , Terstappen Leon W. M. M. , Nanou Afroditi , Neubauer Hans , Rahbari Nuh N. , Knoefel Wolfram T. , Stoecklein Nikolas H. , Neves Rui P. L.
Published: January 2025

Background

Circulating tumour cells (CTCs) and tumour-derived extracellular vesicles (tdEVs) have great potential for monitoring therapy response and early detection of tumour relapse, facilitating personalized adjuvant therapeutic strategies. However, their low abundance in peripheral blood limits their informative value. In this study, we explored the presence of CTCs and tdEVs collected intraoperatively from a tumour-draining vein (DV) and via a central venous catheter (CVC) prior to tumour resection.

Methods

CellSearch analyses of 395 blood samples from 306 patients with gastrointestinal tumours and 93 blood samples from healthy donors were used to establish and validate gates for the automated detection of CTCs and tdEVs with ACCEPT software and R scripts. The selected gate settings were applied to 227 samples of 142 patients with colorectal cancer (CRC) from two independent collectives. Phenotypic features were obtained via numeric analysis of their fluorescence signals (e.g. size, shape, and intensity) and were used for calculating diversity using Shannon index (SI) of clusters generated via the k-means algorithm after Uniform Manifold Approximation and Projection (UMAP) pre-processing, and standard deviation (SD).

Results

CTCs and tdEVs were more abundant in the DV samples compared to CVC samples (p < 0.05). tdEVs were detected in higher numbers than CTCs in both compartments. Importantly, tdEVs in CVCs were associated with tumor spread, whereas CTCs in DVs were linked to tumor size. In both compartments, the prognostic value of tdEVs for overall survival (OS) surpassed that of CTCs, as demonstrated by univariate, multivariate, and Kaplan-Meier analyses. CTCs and tdEVs in DVs were phenotypically distinct, being larger, more eccentric, and displaying stronger cytokeratin intensities (p < 0.05) compared to those in CVC samples. Furthermore, increased diversity in CTC and tdEV phenotypes was significantly associated with shorter survival, validating the prognostic relevance of the SD-diversity metric.

Conclusion

Our study demonstrates that DV sampling significantly enhances the detection of prognostically relevant CTCs and tdEVs in CRC patients, underscoring the superior prognostic significance of tdEVs compared to CTCs. Importantly, the combined phenotypic diversity of both markers emerges as a more powerful biomarker than their enumeration alone. These findings suggest that comprehensive, automated analysis of CTCs and tdEVs in DVs may open new avenues for tailoring individualized therapies in CRC patients.
Batch and semi-continuous fermentation with Parageobacillus thermoglucosidasius DSM 6285 for H2 production
Authors: Ardila Magda S. , Aliyu Habibu , de Maayer Pieter , Neumann Anke
Published: January 2025

Background

Parageobacillus thermoglucosidasius is a facultatively anaerobic thermophile that is able to produce hydrogen (H2) gas from the oxidation of carbon monoxide through the water–gas shift reaction when grown under anaerobic conditions. The water–gas shift (WGS) reaction is driven by a carbon monoxide dehydrogenase–hydrogenase enzyme complex. Previous experiments exploring hydrogenogenesis with P. thermoglucosidasius have relied on batch fermentations comprising defined media compositions and gas atmospheres. This study evaluated the effects of a semi-continuous feeding strategy on hydrogenogenesis.

Results

A batch and two semi-continuous fermentations, with feeding of the latter fresh media (with glucose) in either 24 h or 48 h intervals were undertaken and H2 production, carbon monoxide dehydrogenase (CODH) activity, and metabolite consumption/production were monitored throughout. Maximum H2 production rates (HPR) of 0.14 and 0.3 mmol min−1, were observed for the batch and the semi-continuous fermentations, respectively. Daily feeding attained stable H2 production for 7 days, while feeding every 48 h resulted in high variations in H2 production. CODH enzyme activity correlated with H2 production, with a maximum of 1651 U mL−1 on day 14 with the 48 h feeding strategy, while CODH activity remained relatively constant throughout the fermentation process with the 24 h feeding strategy.

Conclusions

The results emphasize the significance of a semi-continuous glucose-containing feed for attaining stable hydrogen production with P. thermoglucosidasius. The semi-continuous fermentations achieved a 46% higher HPR than the batch fermentation. The higher HPRs achieved with both semi-continuous fermentations imply that this approach could enhance the biohydrogen platform. However, optimizing the feeding interval is pivotal to ensuring stable hydrogen production.
Seismic and GNSS strain-based probabilistic seismic hazard evaluation for northern Chile using DAS Magnitude Scale
Authors: Das Ranjit , Meneses Claudio , Wang Hua
Published: January 2025

Background

Probabilistic Seismic Hazard Assessment (PSHA) is a leading methodology for determining key ground motion parameters such as Peak Ground Acceleration (PGA) and spectral acceleration (SA), essential for structural design. This approach uses extensive earthquake data, typically spanning over a century, leveraging frequency and magnitude statistics. However, long-term ground shaking probabilities may not always be accurately captured by traditional data-driven methods. To address these limitations, this study develops a PSHA map for Northern Chile using both seismic and GNSS (Global Navigation Satellite System) data. A curated homogeneous earthquake catalog, based on the advanced seismic moment magnitude scale Mwg(Das Magnitude Scale), replaces the traditional Mw scale to ensure superior accuracy, particularly for intermediate and smaller earthquakes.

Results

Using the earthquake catalog, seismicity parameters ‘a’ and ‘b’ from the Gutenberg-Richter relationship were derived. Seismogenic modeling and Ground Motion Models (GMMs) were applied to estimate ground motion probabilities for a 475-year return period. Additionally, a PSHA map was constructed using GNSS strain rates, translating velocity-derived strain rates into seismic moment rates and ground shaking probabilities for seismic source zones. Comparative analyses revealed higher PGA values from GNSS strain data compared to seismic catalog data. GNSS strain data proved invaluable for refining seismic segmentation in Northern Chile, enhancing the precision of PSHA calculations.

Conclusions

A PSHA map for Northern Chile, synthesizing seismic catalog data and GNSS strain rates using a Logic Tree-based algorithm, has been developed for a 475-year return period. This map provides a critical tool for generating seismic hazard assessments aligned with building codes and emergency planning protocols. By integrating GNSS strain rates and seismic data, this study advances the reliability and accuracy of long-term ground shaking predictions.
Causal estimation of FTX collapse on cryptocurrency: a counterfactual prediction analysis
Authors: Khan Khalid , Khurshid Adnan , Cifuentes-Faura Javier
Published: January 2025

This study uses the Bayesian structural model to assess the causal effect of the futures exchange (FTX) insolvency on cryptocurrencies from October 2022 to December 14, 2022. Findings show that FTX insolvency negatively impacts cryptocurrencies. Moreover, the results indicate rapid divergence from counterfactual predictions, and the actual cryptocurrencies are consistently lower than would have been expected in the absence of the FTX collapse. Cryptocurrency is reacting strongly to the uncertainty caused by insolvency. In relative terms, the collapse of FTX has been highly detrimental to Solana and Ethereum. Furthermore, the outcomes show that cryptocurrencies would not have been negatively affected if the intervention had not occurred. FTX collapsed owing to a mismatch between the assets and liabilities. The industry is still mostly unregulated, and regulators must act quickly, highlighting the need for outstanding innovation and decentralized and trustless technology adoption.
Mir-615-5p inhibits cervical cancer progression by targeting TMIGD2
Authors: Zhao Yan , Chen Haitao , Zhang Wenhui , Shang Wei , Cao Jinwei , Zhao Huijuan , Zou Zhixiang
Published: January 2025

Background

Cervical cancer (CC) is a prevalent gynecological malignancy, contributing to a substantial number of fatalities among women. MicroRNAs (miRNAs) have emerged as promising biomarkers with significant potential for the early detection and prognosis of CC.

Objective

This study aimed to explore the clinical significance and biological role of miR-615-5p in CC, with the goal of identifying novel biomarkers for this disease.

Materials and methods

The levels of miR-615-5p and TMIGD2 mRNA in tissue samples and cells were quantified through quantitative reverse transcription real-time PCR, followed by statistical analyses to investigate the correlation between miR-615-5p and clinical data. The effects of miR-615-5p on the proliferation and metastasis of CC cells were evaluated using the Cell Counting Kit-8 and Transwell assays. The potential mechanism of miR-615-5p was elucidated by bioinformatics analyses and Dual-luciferase reporter assay. Western blotting was employed to measure the protein levels of TMIGD2.

Results

In CC, the downregulation of miR-615-5p was related to poor prognosis and emerged as an independent prognostic factor. The levels of miR-615-5p were reduced in CC cells. miR-615-5p overexpression restrained the proliferation and metastasis of CC cells. Furthermore, TMIGD2 was identified as a target gene regulated by miR-615-5p, and its expression was notably elevated in CC. The influence of miR-615-5p on the biological behaviors of CC cells was mediated through the modulation of TMIGD2.

Conclusions

Downregulation of miR-615-5p was a prognostic indicator of poor prognosis in CC. miR-615-5p exerted its tumor-suppressive effects by inhibiting cell growth and metastasis through the regulation of TMIGD2.
Exploring the effects of elaborated and motivational feedback on learning engagement in online scripted role discussion
Authors: Feng Qinna , Li Wenhao , Zhu Xueping , Li Xiuhan
Published: January 2025

Giving feedback is key to online collaborative discussion, but the impact of feedback on role-scripts in online discussion remains unclear. To address this research gap, a mixed factorial experiment was conducted to investigate the potential effects and interactions of feedback type (elaborated vs. motivational feedback) and scripted roles (yes vs. no) on behavioral, cognitive, and emotional engagement. Fifty participants enrolled in an undergraduate blended course were randomly assigned to a role-script group (n = 25) and a role-free group (n = 25). Both groups received elaborated and motivational feedback sequentially. Mixed ANOVA results showed that (a) scripted roles significantly facilitated behavioral engagement; (b) elaborated feedback intrigued more cognitive engagement compared to motivational feedback; (c) the role-scripting strategy and feedback type had an interaction effect on behavioral engagement; and (d) there was a significant difference in cognitive engagement among various roles. The epistemic network analysis results revealed evolving cognitive engagement patterns associated with distinct roles when exposed to two distinct types of feedback. The implications of these findings for the design and implementation of online discussions are discussed.
Patient-reported outcome measures to assess mental and physical health status, functionality, and quality of life in patients with major depression or schizophrenia
Authors: San Luis , Arranz Belen , Romans Carlota , García Berta , Coromina Marta , Ortiz Sonia , Vilaplana Miriam , Soto Víctor , Villaescusa Ruth , Alvaros Joan
Published: January 2025

Background

Patient-reported outcomes measures (PROMs) are standardized self-administered tools that assess the patient’s opinion on the level of health, quality of life, and disability among other aspects. The objective of this study was to gather information on physical and mental health in patients with major mental illness using PROMs.

Methods

This was an observational, naturalistic, prospective study carried out in adult stabilized outpatients attended at nine Adult Mental Health Centers in Barcelona, Spain. All participants had a confirmed diagnosis of major depression disorder or schizophrenia (DSM-5) and were currently on drug treatment. Participants (n = 508) self-completed a baseline questionnaire for clinical data and PROMs scales (PHQ-19, SF-12, and WHODAS 2.0) at baseline and 9 months thereafter (n = 482).

Results

Mean (SD) age was 50.9 (13.2) years, and 83% of patients lived with their families. Although 93.9% of patients recognized having a mental illness, 15.7% did not know their diagnosis. When asked if they considered that during the last year their treatment had offered some type of improvement, 83.9% answered affirmatively. Patients reported that their degree of adherence to treatment was high (77%) and most of them (80%) believed the medication had a beneficial effect. Depressed patients showed both at baseline and at follow up significantly more depressive symptoms than the group with schizophrenia. In the schizophrenia group, a statistically significant improvement in depressive symptoms was noted at 9 months follow-up. We did not find significant differences within or between groups in quality of life (SF-12 scores) obtained at baseline and after 9 months of follow-up Both at baseline and at follow-up, patients with depression reported a significantly higher degree of disability (WHODAS scores) than those with schizophrenia.

Conclusions

PROMs can be used in real-world conditions to assess severity of disease, quality of life, and disability in major depression and schizophrenia. The present results are relevant for both patients and clinicians.
Validation of Härtel Surface Anatomical Landmarks for Locating the Foramen Ovale: A Computed Tomography Scan Analysis and Revised Technique Description
Authors: Saavedra Azcona Tomás , Villaescusa Miguel , Casto Florencia , Paolinelli Pablo , Dover Sophia E. , Plou Pedro L. , Ciraolo Carlos A. , Ajler Pablo M.
Published: January 2025

BACKGROUND AND OBJECTIVES:

Härtel triangle provides surface landmarks for locating the foramen ovale (FO) when performing trigeminal nerve percutaneous procedures. Although widely adopted in clinical practice, there is no report that these landmarks have ever been formally validated through modern imaging techniques. Here we aim to validate Härtel anatomical landmarks using computed tomography scans and propose technical considerations for percutaneous trigeminal procedures.

METHODS:

Retrospective analysis of 198 FO from 99 adult head computed tomography scans. Measurements included distances from FO to external auditory canal (EAC), FO to midline, eye's midpupillary (MP) line to midline, and eye's inner canthus (IC) line to midline. Statistical analysis was performed, and results were compared with Härtel description.

RESULTS:

The mean distance from EAC to FO was 23.26 mm (SD: 3.00 mm). Distance from midline to FO was 25.43 mm overall (SD: 1.87 mm). Distance from midline to MP line was measured at 31.96 mm (SD: 1.89 mm). The mean distance from midline to IC line was 14.68 mm (SD: 1.73 mm).

CONCLUSION:

Härtel landmarks can be adjusted for greater accuracy when performing percutaneous trigeminal nerve procedures. The FO is located closer to the EAC and more medially situated than previously assumed. Revised technique suggests aiming the needle trajectory approximately 2 to 2.5 cm anterior to the tragus and targeting a point between the IC and MP lines rather than directly along the MP line. Excessive medial and posterior needle displacement should be avoided to prevent inadvertent vascular injury. These adjustments could enhance procedural accuracy and safety, improving patient outcomes.
rRFtargetDB: a database of Ago1-mediated targets of ribosomal RNA fragments
Authors: Guan Lingyu , Vaidhyanathan Sathyanarayanan , Grigoriev Andrey
Published: January 2025

rRNA-derived fragments (rRFs) are a class of emerging post-transcriptional regulators of gene expression likely binding to the transcripts of target genes. However, the lack of knowledge about such targets hinders our understanding of rRF functions or binding mechanisms. The paucity of resources supporting the identification of the targets of rRFs creates a bottleneck in the fast-developing field. We have previously analyzed chimeric reads in crosslinked Argonaute1-RNA complexes to help infer the guide-target pairs and binding mechanisms of multiple rRFs based on experimental data in human HEK293 cells. To efficiently disseminate these results to the research community, we designed a web-based database rRFtargetDB that preserves most of the experimental results after removal of noise and has a user-friendly interface with flexible query options and filters allowing users to obtain comprehensive information on rRFs (or targets) of interest. rRFtargetDB is populated by ~163,000 experimentally determined unique rRF-mRNA pairs (~60,000 supported by ≥2 reads). Almost 30,000 rRF isoforms produced >385 000 (>156 000 with ≥2 reads) chimeras with all types of RNA targets (mRNAs and non-coding RNAs). Further analyses suggested hypothetical modes of interactions, supported by secondary structures of potential guide-target hybrids and binding motifs, essential for understanding the targeting mechanisms of rRFs. All these results (ranging from the weakest to the strongest experimental support) are presented in rRFtargetDB, whose goal is to provide a resource for building users’ hypotheses on potential roles of rRFs. Further, we illustrate the value/application of the database on several examples. rRFtargetDB is freely accessible at https://grigoriev-lab.camden.rutgers.edu/tardb
Πιθανοτική βραχυπρόθεσμη πρόβλεψη παραγωγής από αιολικά και φωτοβολταϊκά συστήματα με τεχνικές μηχανικής μάθησης
Authors: Μπαζιώνης Ιωάννης
Published: January 2025

Η παρούσα διδακτορική διατριβή, αναπτύσσοντας πρωτότυπα μοντέλα πρόβλεψης της αιολικής και φωτοβολταϊκής παραγωγής, συμβάλλει στη διείσδυση της αιολικής και φωτοβολταϊκής παραγωγής στα συστήματα ηλεκτρικής ενέργειας. Αρχικά, παρουσιάζονται οι κατηγορίες μοντέλων πρόβλεψης που έχουν αναπτυχθεί ανά τα χρόνια για την επιτυχή και ακριβή πρόβλεψη από συστήματα αιολικής και φωτοβολταϊκής παραγωγής αλλά και οι βασικότεροι παράγοντες που επηρεάζουν την ακρίβεια της πρόβλεψης. Ιδιαίτερη έμφαση δίνεται στην ανάλυση των Τεχνητών Νευρωνικών Δικτύων, που στα πλαίσια εξέλιξης του κλάδου της μηχανικής μάθησης έχουν παίξει καθοριστικό ρόλο στη βελτίωση της απόδοσης των μοντέλων πρόβλεψης ενέργειας από Ανανεώσιμες Πηγές. Σε αυτό το πλαίσιο και εστιάζοντας στην κατανόηση της αβεβαιότητας που περιέχεται σε μια διαδικασία πρόβλεψης παραγωγής ενέργειας, προτείνεται ένα καινοτόμο, υβριδικό μοντέλο βραχυπρόθεσμης πρόβλεψης αιολικής παραγωγής, στηριζόμενο σε τεχνικές μηχανικής μάθησης. Ένας βελτιστοποιημένος αλγόριθμος σμήνους προσαρμόζεται και εφαρμόζεται στην προτεινόμενη μεθοδολογία για την βελτιστοποίηση των υπερπαραμέτρων της προτεινόμενης αρχιτεκτονικής. Το μοντέλο εφαρμόζεται σε πραγματικά δεδομένα αιολικών συστημάτων. Η αποτελεσματικότητα του μοντέλου αποδεικνύεται μέσω της σύγκρισης των αποτελεσμάτων που προκύπτουν με τελευταίας τεχνολογίας μοντέλα πιθανοτικής πρόβλεψης αιολικής παραγωγής.Στη συνέχεια, εστιάζοντας στην πρόβλεψη παραγωγής ενέργειας από φωτοβολταϊκά συστήματα, αναπτύσσεται ένα πρωτότυπο, υβριδικό μοντέλο βραχυπρόθεσμης, πιθανοτικής πρόβλεψης, κατάλληλο για την πρόβλεψη φωτοβολταϊκής παραγωγής. Ένας πολύπλοκος, βελτιωμένος αλγόριθμος τύπου σμήνους κοτόπουλων προσαρμόζεται στην αρχιτεκτονική του προτεινόμενου μοντέλου, καταφέρνοντας να βελτιώσει την απόδοσή του, αποφεύγοντας παράλληλα να επιβαρύνει το υπολογιστικό κόστος της μεθοδολογίας. Επιπλέον, ένας μηχανισμός θηράματος-θηρευτή ενσωματώνεται στο τελικό υβριδικό μοντέλο για να βελτιώσει εκ νέου τις δυνατότητες αναζήτησης του προτεινόμενου μοντέλου για τη βέλτιστη δυνατή πρόβλεψη. Το μοντέλο εφαρμόζεται σε πραγματικά δεδομένα φωτοβολταϊκών συστημάτων. Τα τελικά αποτελέσματα αναδεικνύουν, τόσο την ανωτερότητα του προτεινόμενου μοντέλου πρόβλεψης έναντι μοντέλων τελευταίας τεχνολογίας στα οποία εφαρμόστηκαν τα διαθέσιμα δεδομένα, όσο και τη δυνατότητα εφαρμογής του μοντέλου σε πραγματικά προβλήματα πρόβλεψης φωτοβολταϊκής παραγωγής.Συμπερασματικά, τα προτεινόμενα μοντέλα εισάγουν ένα καινοτόμο πλαίσιο μεθοδολογιών πιθανοτικής βραχυπρόθεσμης πρόβλεψης με υβριδικές μεθόδους μηχανικής μάθησης, που συμβάλλουν στη διείσδυση της αιολικής και φωτοβολταϊκής παραγωγής στα συστήματα ηλεκτρικής ενέργειας.