bluuebunny/crossref_metadata_2025 huggingface dataset:
Sternal fixation for traumatic sternal fractures demonstrates better long‐term quality of life outcomes than nonoperative management: A survey analysis
Authors: Bauman Zachary M. , Todd Sydney J. , Khan Hason , Raposo‐Hadley Ashley , Cantrell Emily , Matos Miguel , Sheppard Olabisi , Kamien Andrew , Daubert Trevor , Cemaj Samuel , Evans Charity H. , Nguyen Jonathan , Berning Bennett
Published: March 2024

Introduction

Sternal fractures are rare, causing significant pain, respiratory compromise, and decreased upper extremity range of motion. Sternal fixation (SF) is a viable treatment option; however, there remains a paucity of literature demonstrating long‐term benefits. This study examined long‐term outcomes of SF, hypothesizing they have better long‐term quality of life (QoL) than patients managed nonoperatively (NOM).

Methods

This was a survey study at our level 1 academic hospital. All patients diagnosed with a sternal fracture were included from January 2016 to July 2021. Patients were grouped whether they received SF or NOM. Basic demographics were obtained. Three survey phone call attempts were conducted. The time from injury to survey was recorded. Outcomes included responses to the QoL survey, which included mobility, self‐care, usual activities, chest pain/discomfort, and anxiety/depression. The survey scale is 1–5 (1 = worst condition possible; 5 = best possible condition). Patients were asked to rate their current health on a scale of 0–100 (100 being the best possible health imaginable). Chi square and t‐tests were used. Significance was set at p < 0.05.

Results

Three hundred eighty four patients were surveyed. Sixty nine underwent SF and 315 were NOM. Thirty‐eight (55.1%) SF patients and 126 (40%) NOM patients participated in the survey. Basic demographics were similar. Average days from sternal fracture to survey was 1198 (±492) for the SF group and 1454 (±567) for the NOM group. The SF cohort demonstrated statistically significant better QoL than the NOM cohort for all categories except anxiety/depression.

Conclusion

SF provides better long‐term QoL and better overall health scores compared to NOM.
Treatment of local recurrence of esophageal cancer following Ivor‐Lewis esophagectomy—Experiences of a high‐volume center
Authors: Knipper Karl , Krey Thaddaeus , Lyu Su Ir , Jung Jin‐On , Wirsik Naita M. , Fuchs Hans F. , Schröder Wolfgang , Schlößer Hans A. , Popp Felix C. , Quaas Alexander , Bruns Christiane J. , Schmidt Thomas
Published: March 2024

Purpose

Patients with local recurrence of esophageal cancer have a highly decreased overall survival. There is currently no standardized treatment algorithm for this group. This retrospective cohort study aimed to evaluate the survival of patients with local recurrence, despite receiving individualized treatment options.

Methods

241 of 1791 patients were diagnosed with a local recurrence following Ivor‐Lewis esophagectomy at the University Hospital of Cologne. 59 patients, who were diagnosed only with a local recurrence of adeno‐ or squamous cell carcinoma and received their individualized therapy regimes at our high‐volume center, were included.

Results

The study included 52 patients with adenocarcinoma and 7 with squamous cell carcinoma. Among these, 6 patients underwent resection, 19 received solely chemotherapy, 29 received chemoradiotherapy, and 5 were provided with best supportive care. Patients who underwent resection showed a better survival outcome compared to patients without resection (median OS: not reached vs. 15.1 months, p = 0.012). Best supportive care and palliative care were found to be independent risk factors for shorter overall survival compared to curative intended treatment options like local resection or chemoradiotherapy.

Conclusion

In this study, different treatment strategies for patients with local recurrence of esophageal cancer were depicted. Resection as well as chemoradiotherapy could play a role in selected patients. Further prospective studies are needed to improve the selection of eligible patients.
The UK: Brexit and Competing Populism
Authors: Oh Dayei , Castrén Olli
Published: March 2024

The chapter discusses the political context and political communication environment in the UK during the 2019 EP election. Particular attention is given to the role of Twitter in the UK’s political communication and populism in the party field during the twenty-first century. The empirical Twitter analysis focuses on 7296 tweets sent from 966 Twitter accounts by various political actors in May 2019. The 2019 election was the UK’s last participation in the EP elections before the country left the EU following the 2016 Brexit referendum. As the two major political parties, Conservatives and Labour, refrained from the 2019 EP election debates, smaller Europhilic parties (e.g., Liberal Democrats, Change UK, SNP, Green, Cymru) and Eurosceptic parties (e.g., UKIP, Brexit Party) dominated the Twittersphere. Brexit and the EU were popular themes in the British tweets alongside tweets encouraging supporters to vote and attacking rival political parties. Topic modelling shows differences in the debates on the EU, Brexit, the populist construction of ‘the people’ and media, as well as economic and environmental issues between regions and across the Europhilic and Eurosceptic parties. Network analysis demonstrates that the British Twittersphere was clustered into two antagonistic camps divided by their stance on Brexit. In this, the UK represented a clear case of competing populism.
Fire Severity as a Determinant of the Socioeconomic Impact of Wildfires
Authors: Marcos E. , Fernández-Guisuraga J. M. , Fernández-García V. , Fernández-Manso A. , Quintano C. , Suárez-Seoane S. , Calvo L.
Published: March 2024

Fire has played a crucial role in shaping Earth's landscapes for millions of years and has been used as a cultural tool for human development for millennia. However, changing fire regimes driven by global change drivers and human influences are reshaping landscapes and leading to more severe wildfires, with significant socioeconomic and environmental consequences. These wildfires have substantial direct impacts on human lives, properties, and mental health, as well as indirect impacts on ecosystem services, negatively affecting provisioning, regulating, and cultural services. In general, severe wildfires disrupt the functioning of ecosystems and the subsequent recovery of the ecosystems services. Remote sensing techniques represent efficient tools for monitoring post-fire ecosystem service recovery. On the other hand, the impact of large fires is perceived differently by society influenced by socioeconomic factors, previous experiences, and community dynamics. Understanding these perceptions is essential for developing effective wildfire management and mitigation strategies at the local level. To address the challenges posed by changing fire regimes, a Fire Smart Territory (FST) approach could be considered, emphasizing integrated fire management that considers prevention, effective response, and post-fire restoration. This approach presented in this book chapter also promotes the involvement of local communities in fire prevention and management. So, the conservation of ecosystem services in fire-prone areas requires a holistic and adaptive approach that incorporates ecological knowledge, societal needs, and sustainable land management practices. By adopting an FST framework and considering the complex interactions between fire, ecosystems, and human communities, it is possible to mitigate the impacts of wildfires and promote resilience in these vulnerable landscapes.
Regional Issues of Fire Management: The Role of Extreme Weather, Climate and Vegetation Type
Authors: Pereira M. G. , Nunes J. P. , Silva J. M. N. , Calheiros T.
Published: March 2024

It is of paramount importance to discuss and reflect on the influence that climate and land management have on fire regimes and, consequently, on the regional character of fire management. Our focus is on the Iberian Peninsula, although the results and conclusions presented here are common to many other regions of the world with a Mediterranean climate. The discussion is based on the concept of risk, starting with conjunctural risk factors, moving on to structural factors and including their interconnection. Conjunctural risk factors of weather and climate are discussed in the context of requirements for fire to occur, which include the existence of fuels, a state of dryness suitable for combustion and a source of ignition. The influence of climate and weather is discussed at different space–time scales and related to characteristics of vegetation and land management. The roles of atmospheric patterns, types of weather, extreme events, meteorological hazard indices in patterns of fire incidence, their grouping and definition of pyro-regions are presented. Within structural factors, human populations shape fire regimes by changing the ignition patterns, fighting wildfires, modifying landscapes (e.g., urbanization, deforestation and afforestation) and changing land management. Finally, the interconnection between these risk factors in the context of global changes, in particular climate change, and the challenges they pose to the regional landscape, forest and fire management are highlighted.
Decision Systems in Disaster Management with Application to Fire
Authors: Bostenaru Dan Maria , Crăciun Cerasella , Ibric Adrian
Published: March 2024

This book chapter explores the utilization of an ontology of disaster images in the design of a decision support system for intervening in prevention or reconstruction efforts following events such as earthquakes, floods, and even fires. Grounded in philosophy, ontology in computer science relies on taxonomies, which are classifications of concepts used to facilitate object-oriented programming. To this end, existing collections of disaster images have been analyzed based on relevant literature. The objective here is to map the perception of disasters across different groups, including experts, the passive public, and actively affected individuals. These stakeholders play a crucial role in decision-making within a participatory planning framework, with the most advanced form being strategic planning. This approach offers an alternative to traditional urban regulatory and landscape planning. Urban planning and land use are essential considerations for non-structural disaster prevention interventions, particularly in areas where urban and wildland environments intersect. In such contexts, the coexistence of human settlements and forests in urban settings emphasizes the dual nature of forests as both natural heritage and a domain that calls for nature-based solutions.
Before the Boom: The Historical Background
Authors: O’Malley Eoin
Published: March 2024

The Celtic tiger boom was a major departure from previous experience since the Irish economy had a long previous history of relative weakness compared to many other European countries. The Irish economy had a chronic problem with insufficient generation of employment, resulting in high rates of emigration, as well as relatively low incomes. Previous attempts to promote industrial development included a period of protection and a focus on indigenous industry, followed by a more externally oriented free trade approach with a welcome for foreign investment after the late 1950s. By the mid-1980s, just before the boom, the economy was facing very serious problems, with record unemployment, a high rate of emigration and a major government financial crisis, as well as an industrial sector that was in crisis and an industrial policy that appeared to be failing.
Conclusion
Authors: O’Malley Eoin
Published: March 2024

Foreign direct investment was a major part of the explanation for the boom. A substantial surge in FDI coming into the EU was brought on by the Single European Market and by the rise of new high-tech industries. Ireland’s share of FDI in the EU was increased by Ireland’s existing tax incentives being particularly attractive for the type of companies that predominated in those rising new industries, and by a focus in Irish education on preparing graduates for those industries. It was possible for FDI to have a major impact on the overall economy because the Irish economy was relatively small and open. Increased growth in Irish indigenous companies, assisted by new industrial policy measures, also played a part. Strong growth in demand in export markets, the EU structural funds and social partnership all helped to boost growth. Heavy reliance on FDI may be a strategy that could work out well for Ireland in some periods, but it is a strategy with significant risks. To achieve more sustainable results, Ireland needs to put greater emphasis on the development of indigenous companies.
Konzeptioneller Rahmen
Authors: Tkotzyk Vanessa
Published: March 2024

Das zweite Kapitel dieser Arbeit ist in drei Bereiche unterteilt. Um die Grundlage zur Analyse der Interviews hinsichtlich der Erforschung der Frage, warum Japanerinnen und Japaner nach Deutschland migrieren und sich hier niederlassen, zu schaffen, wird zunächst in Abschnitt 2.1.1 der Begriff der Migration erläutert und es wird mithilfe des „Kaigai Zairyū Hōjinsū Chōsa Tōkei (Annual Report on Japanese Nationals Living Abroad)“, der Angaben des Statistikamtes des Ministeriums für öffentliche Verwaltung, Inneres, Post und Telekommunikation (Sōmushō Tōkei Kyoku) und der Daten der GENESIS-Datenbank ein erster Überblick über mögliche Migrationsgründe gegeben. Im Anschluss daran, in Abschnitt 2.1.2, folgt ein Überblick über die Migrationstheorien und damit die Grundlage für die Interpretation der Ergebnisse der qualitativen Studie zum Migrationsverhalten der permanent ansässigen Japanerinnen und Japaner.
Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy
Authors: Campos-Díaz Aurora , Morejón-García Patricia , Monte-Serrano Eva , Ros-Pardo David , Marcos-Alcalde Iñigo , Gómez-Puertas Paulino , Lazo Pedro A.
Published: March 2024

Rare recessive variants in the human VRK1 gene are associated with several motor neuron diseases (MND), such as amyotrophic lateral sclerosis, spinal muscular atrophy, or distal hereditary motor neuropathies (dHMN). A case with dHMN carrying two novel VRK1 gene variants, expressing Leu200Pro (L200P) and Arg387His (R387H) variant proteins, identified that these protein variants are functionally different. The Leu200Pro variant shares with several variants in the catalytic domain the loss of the kinase activity on different substrates, such as histones, p53, or coilin. However, the distal Arg387His variant and the distal Trp375* (W375X) chinese variant, both located at the end of the low complexity C-terminal region and proximal to the termination codon, retain their catalytic activity on some substrates, and mechanistically their functional impairment is different. The L200P variant, as well as most VRK1 pathogenic variants, impairs the phosphorylation of BAF and histone H4K16 acetylation, which are required for DNA attachment to the nuclear envelope and chromatin accessibility to DNA repair mechanisms, respectively. The R387H variant impairs phosphorylation of H2AX, an early step in different types of DNA damage responses. The functional variability of VRK1 protein variants and their different combinations are a likely contributor to the clinical phenotypic heterogeneity of motor neuron and neurological diseases associated with rare VRK1 pathogenic variants.

Key messages

VRK1 variants implicated in motor neuron diseases are functionally different.

The L200P variant is kinase inactive, and the R387H variant is partially active.

VRK1 variants alter H4K16 acetylation and loss of coilin and BAF phosphorylation.

VRK1 variants alter Cajal bodies and DNA damage responses.

VRK1 variant combination determines the neurological phenotype heterogeneity.
A thermo-mechanically coupled constitutive model for semi-crystalline polymers at finite strains: Mechanical and thermal characterization of polyamide 6 blends
Authors: Reuvers Marie-Christine , Kulkarni Sameer , Boes Birte , Felder Sebastian , Wutzler André , Johlitz Michael , Lion Alexander , Brepols Tim , Reese Stefanie
Published: March 2024

In the field of material modeling, thermoplastic polymers are often studied because of their complex material behavior and their prevalence in industry applications due to their low cost and wide range of applications. Nowadays, where reusability becomes more and more important, materials which can undergo reversible thermomechanical deformations are appealing for, e.g., the construction of car body components. To predict such complex forming processes with multiple influencing factors, such as temperature, strain rate or underlying material morphology, model formulations are needed that account for these influences simultaneously and are validated against experimental data. Unfortunately, up to now only a few contributions are available which consider all these phenomena. In addition, the range of process parameters considered is often narrow due to the experimental effort required for testing. This usually results in limited predictive capabilities of the model. To overcome these limitations, in this work, a thermo-mechanically coupled material model is developed that accounts for the underlying morphology in terms of the degree of crystallinity (DOC). The model formulation is derived in a thermodynamically consistent manner, incorporating coupled nonlinear visco-elastic and elasto-plastic material behavior at finite strains. To characterize and further validate the model, mechanical as well as thermal experiments are conducted for polyamide 6 (PA6). Here, a blending strategy of PA6 together with an amorphous co-polymer is introduced during specimen production to achieve a wider range of stable DOCs(approximately 15%). The model formulation is successfully applied to experimental results and its predictions are in good agreement with experimental observations.
SFRP1 decreases WNT-Mediated M2 macrophage marker expression in breast tissue
Authors: Gregory Kelly J. , Mason Holly , Casaubon Jesse , Schneider Sallie S.
Published: March 2024

The Wnt family of secreted proteins are involved in mammary gland development and tumorigenesis. It has recently been shown that Wnt ligands promote M2 macrophage polarization and so we sought to determine the effects of a Wnt signaling antagonist, Secreted Frizzled Related Protein 1 (SFRP1), on M2 marker expression. We measured a murine M2 marker (Arg1) in mice with a targeted deletion of Sfrp1 during different stages of mammary gland development including puberty, pregnancy, and lactation, as well as in response to obesity. Next, to determine whether Wnt signaling/antagonism affects human M2 markers (CD209 and CCL18), we treated a human patient derived explant (PDE) breast tissue sample with exogenous Wnt3a in the presence and absence of rSFRP1. Finally, we expanded our PDE study to 13 patients and performed bulk RNAseq analysis following the treatment described above. We found that in loss of Sfrp1 in the murine mammary gland increased Arg1 expression. Moreover, we showed that Wnt3a increases CD209 and CCL18 mRNA and protein expression in breast PDEs and that their expression is decreased in response to rSFRP1. Our RNAseq analysis unveiled novel genes that were affected by Wnt3a treatment and subsequently reversed when rSFRP1 was added. Validation of these data exhibited that chemokines involved in promoting macrophage polarization and cancer metastasis, including CCL11 and CCL26, were stimulated by Wnt3a signaling and their expression was abrogated by treatment with rSFRP1. Our data suggest that SFRP1 may be an important mediator that tempers Wnt signaling in the tumor microenvironment.
Targeting osteosarcoma with canine B7-H3 CAR T cells and impact of CXCR2 Co-expression on functional activity
Authors: Cao Jennifer W. , Lake Jessica , Impastato Renata , Chow Lyndah , Perez Luisanny , Chubb Laura , Kurihara Jade , Verneris Michael R. , Dow Steven
Published: March 2024

The use of large animal spontaneous models of solid cancers, such as dogs with osteosarcoma (OS), can help develop new cancer immunotherapy approaches, including chimeric antigen receptor (CAR) T cells. The goal of the present study was to generate canine CAR T cells targeting the B7-H3 (CD276) co-stimulatory molecule overexpressed by several solid cancers, including OS in both humans and dogs, and to assess their ability to recognize B7-H3 expressed by canine OS cell lines or by canine tumors in xenograft models. A second objective was to determine whether a novel dual CAR that expressed a chemokine receptor together with the B7-H3 CAR improved the activity of the canine CAR T cells. Therefore, in the studies reported here we examined B7-H3 expression by canine OS tumors, evaluated target engagement by canine B7-H3 CAR T cells in vitro, and compared the relative effectiveness of B7-H3 CAR T cells versus B7-H3-CXCR2 dual CAR T cells in canine xenograft models. We found that most canine OS tumors expressed B7-H3; whereas, levels were undetectable on normal dog tissues. Both B7-H3 CAR T cells demonstrated activation and OS-specific target killing in vitro, but there was significantly greater cytokine production by B7-H3-CXCR2 CAR T cells. In canine OS xenograft models, little anti-tumor activity was generated by B7-H3 CAR T cells; whereas, B7-H3-CXCR2 CAR T cells significantly inhibited tumor growth, inducing complete tumor elimination in most treated mice. These findings indicated therefore that addition of a chemokine receptor could significantly improve the anti-tumor activity of canine B7-H3 CAR T cells, and that evaluation of this new dual CAR construct in dogs with primary or metastatic OS is warranted since such studies could provide a critical and realistic validation of the chemokine receptor concept.
Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma
Authors: He Yijia , Liu Lingyun , Dong Yuexin , Zhang Xiaoxin , Song Yuxian , Jing Yue , Ni Yanhong , Wang Yi , Wang Zhiyong , Ding Liang
Published: March 2024

Background

Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC).

Methods

PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis.

Results

Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3high tumor showed high proliferation index with metastasis potential, accompanied with less CD3+CD8+ T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8+ T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3highB7-H2high tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285–6.851).

Conclusions

LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.
IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models
Authors: Yu Justin , Gadwa Jacob , Ross Richard B. , Knitz Michael , Darragh Laurel B. , Abdelazeem Khalid N. M. , Beynor Jessica , Neupert Brooke , Nguyen Alexander , Nguyen Diemmy , Olimpo Nicholas , Corbo Sophia , Van Court Benjamin , D’Alessandro Angelo , Saviola Anthony , Karam Sana D.
Published: March 2024

Clinically approved head and neck squamous cell carcinoma (HNSCC) immunotherapies manipulate the immune checkpoint blockade (ICB) axis but have had limited success outside of recurrent/metastatic disease. Interleukin-7 (IL7) has been shown to be essential for effector T-cell survival, activation, and proliferation. Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models. Immune populations from the tumor, draining lymph nodes, and blood were compared between treatment groups and controls using flow cytometry, proteomics, immunofluorescence staining, and RNA sequencing. Treatment with RT and IL7 (RT + IL7) resulted in significant tumor growth reduction, high CD8 T-cell tumor infiltration, and increased proliferation of T-cell progenitors in the bone marrow. IL7 also expanded a memory-like subpopulation of CD8 T-cells. These results indicate that IL7 in combination with RT can serve as an effective immunotherapy strategy outside of the conventional ICB axis to drive the antitumor activity of CD8 T-cells.
DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy
Authors: Ma Zhe , Zhou Zhenxing , Duan Wenwen , Yao Gaofeng , Sheng Shimei , Zong Sidou , Zhang Xin , Li Changkui , Liu Yuanyuan , Ou Fengting , Dahar Maha Raja , Huang Yanshan , Yu Lushan
Published: March 2024

Background

Claudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma. The T cell engager targeting CLDN18.2 represents a compelling strategy for enhancing anti-cancer efficacy.

Methods

Based on the in-house screened anti-CLDN18.2 VHH, we have developed a novel tri-specific T cell engager targeting CLDN18.2 for gastric and pancreatic cancer immunotherapy. This tri-specific antibody was designed with binding to CLDN18.2, human serum albumin (HSA) and CD3 on T cells.

Results

The DR30318 demonstrated binding affinity to CLDN18.2, HSA and CD3, and exhibited T cell-dependent cellular cytotoxicity (TDCC) activity in vitro. Pharmacokinetic analysis revealed a half-life of 22.2–28.6 h in rodents and 41.8 h in cynomolgus monkeys, respectively. The administration of DR30318 resulted in a slight increase in the levels of IL-6 and C-reactive protein (CRP) in cynomolgus monkeys. Furthermore, after incubation with human PBMCs and CLDN18.2 expressing cells, DR30318 induced TDCC activity and the production of interleukin-6 (IL-6) and interferon-gamma (IFN-γ). Notably, DR30318 demonstrated significant tumor suppression effects on gastric cancer xenograft models NUGC4/hCLDN18.2 and pancreatic cancer xenograft model BxPC3/hCLDN18.2 without affecting the body weight of mice.
Let-7i enhances anti-tumour immunity and suppresses ovarian tumour growth
Authors: Wilkinson Andrew N. , Chen Rui , Coleborn Elaina , Neilson Trent , Le Khang , Bhavsar Chintan , Wang Yue , Atluri Sharat , Irgam Gowri , Wong Kiefer , Yang Da , Steptoe Raymond , Wu Sherry Y.
Published: March 2024

Cancer immunotherapy has seen significant success in the last decade for cancer management by enhancing endogenous cancer immunity. However, immunotherapies developed thus far have seen limited success in the majority of high-grade serous carcinoma (HGSC) ovarian cancer patients. This is largely due to the highly immunosuppressive tumour microenvironment of HGSC and late-stage identification. Thus, novel treatment interventions are needed to overcome this immunosuppression and complement existing immunotherapies. Here, we have identified through analysis of > 600 human HGSC tumours a critical role for Let-7i in modulating the tumoural immune network. Tumoural expression of Let-7i had high positive correlation with anti-cancer immune signatures in HGSC patients. Confirming this role, enforced Let-7i expression in murine HGSC tumours resulted in a significant decrease in tumour burden with a significant increase in tumour T cell numbers in tumours. In concert with the improved tumoural immunity, Let-7i treatment also significantly increased CD86 expression in antigen presenting cells (APCs) in the draining lymph nodes, indicating enhanced APC activity. Collectively, our findings highlight an important role of Let-7i in anti-tumour immunity and its potential use for inducing an anti-tumour effect in HGSC.
Wall shear stress measurement using a zero-displacement floating-element balance
Authors: Aguiar Ferreira M. , Costa P. , Ganapathisubramani B.
Published: March 2024

The floating-element (FE) principle, introduced nearly a century ago, remains one of the most versatile direct wall shear stress measurement methods. Yet, its intrinsic sources of systematic error, associated with the flow-exposed gap, off-axis load sensitivity, and calibration, have thus far limited its widespread application. In combination with the lack of standard designs and testing procedures, measurement reliability still hinges heavily on individual judgement and expertise. This paper presents a framework to curb these limitations, whereby the design and operation of a FE balance are leveraged by an analytical model that attempts to capture the behaviour and predict the relative contribution of the systematic sources of error. The design is based on a parallel-shift linkage and a zero-displacement force-feedback system. The FE has a surface area of $$200\times 200\,$$

200
×
200

mm, and measurement sensitivity is adjustable depending on the surface condition and the Reynolds number. It is thus suitable for application in a wide range of low-speed, boundary-layer wind tunnels, small or large scale. Measurements of the skin friction coefficient over a smooth wall show a remarkable agreement with oil-film interferometry, especially for $${\rm Re}_{\theta } > 1.3 \times 10^4$$

Re
θ

>
1.3
×

10
4

. The discrepancy relative to the empirical Coles–Fernholz relation ($$\kappa = 0.39$$

κ
=
0.39

and $$C = 4.352$$

C
=
4.352

) is within $$0.5\,$$

0.5

%, and the level of uncertainty is below $$1\,$$

1

% for a confidence interval of $$95\,$$

95

%.
Skin color reporting in squamous cell carcinoma-related randomized controlled trials in top dermatology journals: a systematic review
Authors: Salmen Natasha L. , Menage Klarens , Baumann Anthony N. , Curtis Deven P. , Brodell Robert T.
Published: March 2024

The objectives are to determine the frequency that skin color is reported in randomized controlled trials (RCTs) involving squamous cell carcinoma (SCC) detection and treatment in leading dermatology journals. A systematic review of RCTs involving SCC was conducted among the top ten most impactful dermatology journals from inception to July 10th, 2023. Studies were included if they reviewed the treatment, prevention, or detection of SCC, involved patients directly and were classified as traditional RCTs. Studies were considered positive for reporting SOC if there was any demographic data in the methods or results of the following terms: Fitzpatrick scale, race, ethnicity, sunburn tendency, or skin of color. Of the 39 studies which were identified, 23 reported data related to skin color data (59.0%). White individuals were the most reported in these studies (56.5%). Subgroup analysis was conducted, and no statistical significance was found for study location, year of publication, or funding source. Skin color impacts skin cancer detection, predominant location of tumors, and recurrence. Less than 60% of high-quality RCTs related to SCC in top global dermatology journals included skin color among the demographic traits of study participants. Subgroup analysis demonstrated no improvement in reporting over the past 2 decades. Further research is needed to understand the reason for low skin color reporting rates among SCC-related RCTs and the impact this has on society.
Subcortical auditory system in tinnitus with normal hearing: insights from electrophysiological perspective
Authors: Colak Hasan , Sendesen Eser , Turkyilmaz Meral Didem
Published: March 2024

Purpose

The mechanism of tinnitus remains poorly understood; however, studies have underscored the significance of the subcortical auditory system in tinnitus perception. In this study, our aim was to investigate the subcortical auditory system using electrophysiological measurements in individuals with tinnitus and normal hearing. Additionally, we aimed to assess speech-in-noise (SiN) perception to determine whether individuals with tinnitus exhibit SiN deficits despite having normal-hearing thresholds.

Methods

A total 42 normal-hearing participants, including 22 individuals with chronic subjective tinnitus and 20 normal individuals, participated in the study. We recorded auditory brainstem response (ABR) and speech-evoked frequency following response (sFFR) from the participants. SiN perception was also assessed using the Matrix test.

Results

Our results revealed a significant prolongation of the O peak, which encodes sound offset in sFFR, for the tinnitus group (p < 0.01). The greater non-stimulus-evoked activity was also found in individuals with tinnitus (p < 0.01). In ABR, the tinnitus group showed reduced wave I amplitude and prolonged absolute wave I, III, and V latencies (p ≤ 0.02). Our findings suggested that individuals with tinnitus had poorer SiN perception compared to normal participants (p < 0.05).

Conclusion

The deficit in encoding sound offset may indicate an impaired inhibitory mechanism in tinnitus. The greater non-stimulus-evoked activity observed in the tinnitus group suggests increased neural noise at the subcortical level. Additionally, individuals with tinnitus may experience speech-in-noise deficits despite having a normal audiogram. Taken together, these findings suggest that the lack of inhibition and increased neural noise may be associated with tinnitus perception.
Exposure to psychotropic drugs and breast cancer risk in patients with bipolar disorder and major depressive disorder: a nested case–control study
Authors: Li Dian-Jeng , Tsai Shih-Jen , Chen Tzeng-Ji , Liang Chih-Sung , Chen Mu-Hong
Published: March 2024

Breast cancer is one of the most prevalent and serious types of cancer globally. Previous literature has shown that women with mental illness may have an increased risk of breast cancer, however whether this risk is associated with the use of psychotropic drugs has yet to be elucidated. This study aimed to assess such risk among women with major depressive disorder (MDD) and bipolar disorder (BD). A nested case–control study design was used with data obtained from the Taiwan National Health Insurance Research Database. Logistic regression analysis with adjustments for demographic characteristics, medical and mental comorbidities, and all-cause clinical visits was performed to estimate the risk of breast cancer according to the cumulative defined daily dose (cDDD) of psychotropic drugs. The study included 1564 women with MDD or BD who had breast cancer, and 15,540 women with MDD or BD who did not have breast cancer. After adjusting for important confounders, the long-term use of valproic acid (odds ratio, 95% confidence interval: 0.58, 0.39–0.56, cDDD ≥ 365), citalopram (0.58, 0.37–0.91, cDDD 180–365), and sertraline (0.77, 0.61–0.91, cDDD ≥ 365) was associated with a lower risk of breast cancer compared to a cDDD < 30. The short-term use of fluvoxamine (0.82, 0.69–0.96, cDDD 30–180), olanzapine (0.54, 0.33–0.89, cDDD 30–179), risperidone (0.7, 0.51–0.98, cDDD 30–179), and chlorpromazine (0.48, 0.25–0.90, cDDD 30–179) was associated with a lower risk of breast cancer. We found no evidence of an increased risk of breast cancer in patients with MDD or BD receiving psychotropic drugs.
Factors associated with success of conservative therapy in chronic subdural hematoma: a single-center retrospective analysis
Authors: Foppen Merijn , Lodewijkx Roger , Bandral Harssh Verdan , Yah Kevin , Slot K. Mariam , Vandertop William , Verbaan Dagmar
Published: March 2024

Introduction

Conservative therapy is a viable option for patients with chronic subdural hematoma (cSDH) who express no, or only mild symptoms. It is not clear which factors are associated with success of conservative therapy. This study aims to determine conservative therapy's success rate and to identify features possibly associated with success.

Methods

A monocenter retrospective cohort study, including cSDH patients treated conservatively (wait-and-watch) from 2012 to 2022, was performed. The primary outcome was success of conservative therapy, defined as ‘no crossover to surgery’ during the follow-up period. Secondary outcomes were (1) factors associated with success, analyzed with univariate and multivariable logistic regression analyses, (2) 30-day mortality (3) time to crossover and (4) reasons for crossover.

Results

We included 159 patients. Conservative therapy was successful in 96 (60%) patients. Hematoma volume (OR 0.79, 95% CI 0.69–0.92) and hypodense hematoma type (OR 3.57, 95% 1.38–9.23) were associated with success. Thirty-day mortality rate was 5% and the median duration between diagnosis and surgery was 19 days (IQR 8–39). Clinical deterioration was the most frequent reason for crossover (in 61/63 patients, 97%) and was accompanied by radiological hematoma progression in 42 patients (67%).

Conclusion

In this selected group of patients, conservative therapy was successful in 60%. Smaller hematoma volume and hypodense hematoma type were associated with success. As time until crossover was approximately three weeks, deploying conservative therapy as primary treatment seems safe and could be rewarding as surgical complications can be avoided. Improvement in patient selection in future cohorts remains warranted.
Management and outcomes of bronchiolitis in Italy and Latin America: a multi-center, prospective, observational study
Authors: Camporesi Anna , Yock-Corrales Adriana , Gomez-Vargas Jessica , Roland Damian , Gonzalez Magali , Barreiro Sandra , Morello Rosa , Brizuela Martin , Buonsenso Danilo
Published: March 2024

We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and economic status during to post-pandemic bronchiolitis seasons.  This was a prospective observational cohort study performed in two academic centers in Latin America (LA) and three in Italy. All consecutive children with a clinical diagnosis of bronchiolitis were included, following the same data collection form.  Nine hundred forty-three patients have been enrolled: 275 from the two Latin American Centers (San Jose, 215; Buenos Aires, 60), and 668 from Italy (Rome, 178; Milano, 163; Bologna, 251; Catania, 76). Children in LA had more frequently comorbidities, and only rarely received palivizumab. A higher number of patients in LA had been hospitalized in a ward (64% versus 23.9%, p < 0.001) or in a PICU (16% versus 6.2%, p < 0.001), and children in LA required overall more often respiratory support, from low flow oxygen to invasive mechanical ventilation, except for CPAP which was more used in Italy. There was no significant difference in prescription rates for antibiotics, but a significantly higher number of patients treated with systemic steroids in Italy.

Conclusions: We found significant differences in the care for children with bronchiolitis in Italy and LA. Reasons behind such differences are unclear and would require further investigations to optimize and homogenize practice all over the world.

What is Known:• Bronchiolitis is among the commest cause of morbidity and mortality in infants all over the world.

What is New:• There are significant differences on how clinicians care for bronchiolitis in different centers and continents. Differences in care can be principally due to different local practices than differences in patients severity/presentations.• Understanding these differences should be a priority to optime and standardize bronchiolitis care globally.
The intransitive dice kernel: $$\frac{\mathbbm {1}_{x\ge y}-\mathbbm {1}_{x\le y}}{4} - \frac{3(x-y)(1+xy)}{8}$$
Authors: Sah Ashwin , Sawhney Mehtaab
Published: March 2024

Answering a pair of questions of Conrey, Gabbard, Grant, Liu, and Morrison, we prove that a triplet of dice drawn from the multiset model are intransitive with probability $$1/4+o(1)$$

1
/
4
+
o
(
1
)

and the probability a random pair of dice tie tends toward $$\alpha n^{-1}$$

α

n

-
1

for an explicitly defined constant $$\alpha $$
α
. This extends and sharpens the recent results of Polymath regarding the balanced sequence model. We further show the distribution of larger tournaments converges to a universal tournamenton in both models. This limit naturally arises from the discrete spectrum of a certain skew-symmetric operator (given by the kernel in the title acting on $$L^2([-1,1])$$

L
2

(

[
-
1
,
1
]

)

). The limit exhibits a degree of symmetry and can be used to prove that, for instance, the limiting probability that $$A_i$$

A
i

beats $$A_{i+1}$$

A

i
+
1

for $$1\le i\le 4$$

1
≤
i
≤
4

and that $$A_5$$

A
5

beats $$A_1$$

A
1

is $$1/32+o(1)$$

1
/
32
+
o
(
1
)

. Furthermore, the limiting tournamenton has range contained in the discrete set $$\{0,1\}$$

{
0
,
1
}

. This proves that the associated tournamenton is non-quasirandom in a dramatic fashion, vastly extending work of Cornacchia and Hązła regarding the continuous analogue of the balanced sequence model. The proof is based on a reduction to conditional central limit theorems (related to work of Polymath), the use of a “Poissonization” style method to reduce to computations with independent random variables, and the systematic use of switching-based arguments to extract cancellations in Fourier estimates when establishing local limit-type estimates.
Rotation Inside Convex Kakeya Sets
Authors: Janzer Barnabás
Published: March 2024

Let K be a convex body (a compact convex set) in $$\mathbb {R}^d$$

R

d

, that contains a copy of another body S in every possible orientation. Is it always possible to continuously move any one copy of S into another, inside K? As a stronger question, is it always possible to continuously select, for each orientation, one copy of S in that orientation? These questions were asked by Croft. We show that, in two dimensions, the stronger question always has an affirmative answer. We also show that in three dimensions the answer is negative, even for the case when S is a line segment – but that in any dimension the first question has a positive answer when S is a line segment. And we prove that, surprisingly, the answer to the first question is negative in dimensions four and higher for general S.
iATT liver fat quantification for steatosis grading by referring to MRI proton density fat fraction: a multicenter study
Authors: Hirooka Masashi , Ogawa Sadanobu , Koizumi Yohei , Yoshida Yuichi , Goto Tatsuya , Yasuda Satoshi , Yamahira Masahiro , Tamai Tsutomu , Kuromatsu Ryoko , Matsuzaki Toshihisa , Suehiro Tomoyuki , Kamada Yoshihiro , Sumida Yoshio , Hiasa Yoichi , Toyoda Hidenori , Kumada Takashi
Published: March 2024

Background

Several preliminary reports have suggested the utility of ultrasound attenuation coefficient measurements based on B-mode ultrasound, such as iATT, for diagnosing steatotic liver disease. Nonetheless, evidence supporting such utility is lacking. This prospective study aimed to investigate whether iATT is highly concordant with magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF) and could well distinguish between steatosis grades.

Methods

A cohort of 846 individuals underwent both iATT and MRI-PDFF assessments. Steatosis grade was defined as grade 0 with MRI-PDFF < 5.2%, grade 1 with 5.2% MRI-PDFF < 11.3%, grade 2 with 11.3% MRI-PDFF < 17.1%, and grade 3 with MRI-PDFF of 17.1%. The reproducibility of iATT and MRI-PDFF was evaluated using the Bland–Altman analysis and intraclass correlation coefficients, whereas the diagnostic performance of each steatosis grade was examined using receiver operating characteristic analysis.

Results

The Bland–Altman analysis indicated excellent reproducibility with minimal fixed bias between iATT and MRI-PDFF. The area under the curve for distinguishing steatosis grades 1, 2, and 3 were 0.887, 0.882, and 0.867, respectively. A skin-to-capsula distance of ≥ 25 mm was identified as the only significant factor causing the discrepancy. No interaction between MRI-logPDFF and MRE-LSM on iATT values was observed.

Conclusions

Compared to MRI-PDFF, iATT showed excellent diagnostic accuracy in grading steatosis. iATT could be used as a diagnostic tool instead of MRI in clinical practice and trials.

Trial registration This study was registered in the UMIN Clinical Trials Registry (UMIN000047411).
Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly
Authors: Ding Xiufang , Wang Yue , Zhang Sida , Zhang Ruihua , Chen Dong , Liu Changcai , Xu Jianfu , Chen Long
Published: March 2024

Peptide drugs have disadvantages such as low stability, short half-life and side effects, which limit their widespread use in clinical practice. Therefore, peptide drugs can be modified to improve these disadvantages. Numerous studies have shown that alkyl-modified peptide drugs can self-assemble to prolong the duration of efficacy and/or reduce side effects. However, the commonly used solid-phase synthesis method for alkyl-modified peptides is time-consuming. To overcome this, a simple reductive amination reaction was employed, which can directly graft the alkyl chain to the peptide sequence and effectively avoid stepwise synthesis from C- to N-terminal with amino acids. In this study, ω-conotoxin MVIIA was used as the peptide drug, while myristic aldehyde was used as the alkylating agent. To obtain the maximum productivity of modified peptides, the molar ratio of peptide MVIIA to myristic aldehyde in the reductive amination reaction was optimized. Furthermore, the peptide modification sites in this reaction were confirmed by secondary mass spectrometry analysis. Besides, alkyl-modified peptide MVIIA was able to form micelles by self-assembly and improved stability in serum, which was related to our previous work where myristoylated peptide MVIIA micelles can improve the drug stability. Finally, this study was intended to provide a methodological basis for modifying the alkyl chain of peptide drugs.