bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Tranexamic Acid and Recombinant Activated Factor VII on Traumatic Bleeding and Mortality in Mice
Authors: Chumappumkal Joseph Bilgimol , De Pablo-Moreno Juan Andres , Falah Nicca , Wentzel Abraham , Frias-Anaya Eduardo , von Drygalski Annette
Published: December 2024

Introduction

Trauma-associated bleeding and coagulopathy are often lethal. Early administration of tranexamic acid (TXA) is included in massive transfusion protocols since it somewhat reduces mortality. Recombinant activated factor VIIa (rFVIIa) is used variably during exsanguination when its procoagulant effects may outweigh potential prothrombotic risks. Since a comprehensive understanding of the effects of TXA and rFVIIa on bleeding, coagulopathy, and mortality is lacking, we investigated those in a murine trauma model.

Materials and Methods

C57BL/6J mice (8-10 weeks old, ~20 per group) were pretreated (within 5 minutes of trauma) intravenously with saline, TXA (10mg/kg), or rFVIIa (3mg/kg) and subjected to liver laceration. Blood loss (weighing blood-soaked sponges from the abdomen), coagulopathy [APTT, Factor (F)II, FV, FVIII, FX, and fibrinogen), thrombin-antithrombin (TAT), plasmin-antiplasmin (PAP) complexes, and D-dimer] were analyzed at 60 minutes after trauma. Data were expressed as median and compared by Mann-Whitney test. Seven-day survival was analyzed using Kaplan-Meier curves and pulmonary fibrin burden was determined by Orcein and Martius Scarlet Blue staining.

Results

Blood loss in saline-treated mice (21 µL/g) was reduced significantly by both agents, TXA or rFVIIa (~16 µL/g). Saline-treated mice developed acute traumatic coagulopathy (ATC), characterized by elevated APTT (35 seconds vs 23 seconds baseline [BL]), TAT-complex formation (334 ng/mL vs 7 ng/mL BL), and reductions of FV (14% vs 94% BL) FVIII (4% vs 101% BL)), and fibrinogen (47% vs 99% BL). Consistent with ATC, FII, and FX remained unaffected. Whereas TXA normalized the ATC, rFVIIa over-corrected the APTT, and increased TAT complexes and FVIII levels. While both agents reduced PAP complex formation similarly, suggestive of fibrinolysis control, rFVIIa was unable to suppress D-dimer formation, suggestive of persistent clot turnover. Seven-day survival was ~80% for mice treated with saline or TXA, but only ~50% for mice treated with rFVIIa. Pronounced pulmonary fibrin depositions (luminal thrombi) were noted in the surviving mice treated with rFVIIa, but were absent in TXA-treated mice

Conclusion

Peri-traumatic TXA and rFVIIa resulted in similar bleed reduction. However, while TXA normalized ATC, rFVIIa promoted prothrombotic coagulation abnormalities associated with increased mortality and thromboembolic complications. Since TXA mitigates but does not abolish bleeding and death in humans, our findings highlight the urgent need for alternative, targeted interventions to reduce ATC, traumatic bleeding, and death in humans.
Repolarisation of M2 Macrophages Via Cgas-Sting Activation Enhances Phagocytosis of Acute Myeloid Leukaemia
Authors: Markham Matthew , Maynard Rebecca S , Bell George , Hampton Katherine , Fowler-Shorten Dominic James , Polski-Delve Alyssa Nicole , Altera Annalisa , Taylor Rosie , Hellmich Charlotte , Bowles Kristian , Rushworth Stuart A
Published: December 2024

The tumour microenvironment is composed of extracellular matrix and non-mutated cells supporting tumour growth and development. Tumour-associated macrophages are among the most abundant immune cells in the microenvironment. Studies of the innate immune compartment in the bone marrow of patients with acute myeloid leukaemia (AML) reveal a shift toward a tumour-supportive M2-polarised macrophage (Weinhäuser et al., 2023). Furthermore, previous work by our group has shown that AML drives activation of the stimulator of interferon genes (STING) pathway in macrophages in the AML bone marrow microenvironment (Moore et al., 2022). We found that AML-derived mitochondrial damage-associated molecular patterns were processed by bone marrow macrophages via LC3-associated phagocytosis. This activation of STING resulted in a suppression of AML growth.

To fully characterise the role of STING pathway in AML-associated macrophages we have combined RNA sequencing, flow cytometry and in vivo characterisation to reveal a shift of M2 tumour supportive macrophages towards an M1 phenotype in response to STING activation. We used various STING agonists including DMXAA, 2'3'-cGAMP, and CpG oligonucleotides to model STING activation of bone marrow derived macrophages (BMDM) in vitro. Functionally, STING activation of BMDM induced an anti-tumour response by increasing phagocytosis of AML blasts which was also established in an in vivo model of AML in C57Bl/6 mice. Using the well-established syngeneic AML murine model (MN1), STING activation in vivo slowed tumour progression and prolonged survival. RNA sequencing of STING activation in macrophages revealed a M1 proinflammatory polarisation phenotype. Moreover, AML-induced M2 macrophage polarisation was reversed in response to STING activation.

Additionally, we show that STING activation upregulates genes involved with cell-cell adhesion, and we used blocking antibodies to assess their involvement in the increased phagocytic clearance of AML blasts. We observed that inhibiting the ICAM1/LFA1 interaction blocked STING-induced phagocytosis of AML blasts, therefore demonstrating the role this interaction plays in mediating the anti-tumour response of STING activation. Finally, we show that AML cells have higher levels of LFA1 cell surface expression than non-AML cells within the bone marrow. This is further supported by the BloodSpot database which demonstrates a higher level of LFA1 expression in human AML subtypes compared to haematopoietic stem and progenitor cells (Bagger, F.O. et al., 2016).

Our study provides insight into mechanisms by which AML-associated macrophages can be reprogrammed through STING activation towards an anti-tumour, pro-phagocytic phenotype, thus providing an alternative strategy for targeting leukaemia progression.
Hospital-Acquired Venous Thromboembolism (HA-VTE) Epidemiology and Risk Factors Among Critically Ill Children and Young Adults with Diabetic Ketoacidosis
Authors: DeMayo Kristin , Havlicek Elizabeth , Root Maya , Betensky Marisol , Goldman Zachary , Goldenberg Neil , Sochet Anthony A
Published: December 2024

Introduction: Children hospitalized for diabetic ketoacidosis (DKA) experience hyperglycemic hyperosmolarity and severe dehydration that are considered prothrombotic, heightening the risk of hospital-acquired venous thromboembolism (HA-VTE). Yet, the occurrence rate and risk factors for HA-VTE among cases of pediatric DKA remain ill-defined.

Methods: We performed a retrospective, single center cohort study including children and young adults 0 - 21 years of age hospitalized in the pediatric intensive care unit for DKA from Oct 2020 - December 2023. The primary outcome was radiographically confirmed HA-VTE (i.e., pulmonary embolism, limb/neck deep venous thrombosis, and cerebral sinovenous thromboembolism). Detailed data were collected on HA-VTE (timing, location, central venous catheterization [CVC]-relatedness), DKA (degrees of acidosis and hyperglycemia, β-hydroxybutyrate levels, clinical cerebral edema), thromboprophylaxis (TP) modalities, and putative HA-VTE risk factors (age, inherited coagulopathy, acute and chronic immobility, mechanical ventilation [IMV], infectious comorbidity). Descriptive and comparative (e.g., chi-square, student's t, and Wilcoxon rank sum tests) statistics were performed.

Results: During the study period, 386 children and young adults were hospitalized for DKA of which 2 (0.5%) developed a HA-VTE (both were CVC-related). The children who developed HA-VTE were 13 and 14 years of age, prescribed mechanical TP without pharmacologic TP, treated for acute cerebral edema, profoundly acidotic (β-hydroxybutyrate: 8.5 and 9.6 mmol/L, respectively), acutely immobilized (per Braden QD values), and exhibited plasma hyperosmolarity (339 and 342 mOsm/kg, respectively). Rates of HA-VTE were more common among subpopulations with CVC (40% vs 0%), symptomatic cerebral edema (12.5% vs 0%), undergoing IMV (20% vs 0.2%), and COVID-19 infection (5.6% vs 0.3%) as compared to those without these clinical features.

Conclusion: The observed HA-VTE rate among critically ill children with DKA over a three-year period was 0.5%. Putative risk factors for HA-VTE in this population, including comorbid conditions and markers of disease severity at presentation such as symptomatic cerebral edema, degree of acidosis, CVC, and IMV, should be prospectively investigated.
Management of Upper Extremity Superficial Vein Thrombosis in Patients with Cancer: A Retrospective Observational Cohort Study
Authors: Tokessy Lauren , Brown Cameron , Wang Tzu-Fei , Kimpton Miriam , Carrier Marc
Published: December 2024

Introduction:

Venous thromboembolism (VTE) including superficial vein thromboses are common in patients with cancer. Although clinical studies have reported that anticoagulant therapy may be beneficial in some patients with lower extremity superficial vein thrombosis, the management of upper extremity superficial vein thrombosis (UESVT), especially in patient with cancer, remains unclear. Patients with cancer are at higher risk of both recurrent VTE and bleeding complications while receiving anticoagulant therapy. Hence, the risks and benefits of anticoagulant therapy are unknown in this patient population. We sought to assess the efficacy and safety of anticoagulant therapy in patients with cancer and UESVT.

Methods:

A single center retrospective observational cohort study which included consecutive patients with cancer and UESVT assessed between 2019 and 2023 was conducted. The primary outcome was the extension of the UESVT or recurrence of VTE during a 90-day follow-up period. Secondary outcomes included major bleeding and clinically relevant non-major bleeding (CRNMB), and overall mortality. Major bleeding and CRNMB were defined according to the International Society on Thrombosis and Haemostasis criteria. Outcomes were reported as proportions along with their 95% confidence intervals (CI) during the follow-up period.

Results:

Overall, 86 patients were included in the analyses. The median age was 79±48 years, and 47.7% were female. The most common locations for cancer types were lung (16.3%) and breast (11.6%), and 57.0% in stage 3 or 4. A majority of patients had a central venous catheter in place. A total of 64 (74.4%) patients received anticoagulant therapy, including 27 patients (31.4%) at a therapeutic dosage. The overall rate of UESVT or VTE recurrence was 17.4% (95% CI: 10.1-27.1) over the 90-day follow-up period. There were 2 major bleeding events (2.3%, 95% CI: 0.2-8.2) and 5 CRNMB (5.8%, 95% CI: 1.9-13.1) during the follow-up period. The overall mortality rate was 24.4%.

Conclusion:

In patients with cancer and UESVT, the risk of superficial vein thrombosis extension or recurrent VTE is high despite anticoagulant therapy. Future prospective studies are needed to derive the optima management strategy for this patient population.
Barriers and opportunities for developing, implementing and operating inclusive digital mobility services
Authors: Delaere Hannes , Basu Samyajit , Macharis Cathy , Keseru Imre
Published: December 2024

As digital mobility services increasingly reshape the transportation landscape, offering a multitude of choices for users, a significant lack of equality emerges: vulnerable-to-exclusion groups are often left behind, unable to equally access digital transport services. This study investigates the opportunities to create inclusive and accessible digital mobility services, based on the viewpoints of developers, operators, and policy makers. Through 32 semi-structured interviews with stakeholders, we look into the existing regulatory frameworks, the extent of user involvement in service (re-)development, considerations for data protection and privacy for vulnerable groups, and the financial aspects supporting the development and operation of inclusive digital transport services. A thematic content analysis reveals a complex challenge: a lack of effective communication, collaboration, and co-creation across the majority of services, in combination with a widespread failure to disseminate insights among stakeholders, resulting in a lack of knowledge about vulnerable-to-exclusion groups. Despite a general awareness of the importance of inclusive design, actionable steps to achieve inclusive digital services remain scarce, with only a handful of services actively pursuing these goals. Our findings push for a comprehensive approach that enhances clear communication, stakeholder collaboration, and promotes the co-creation of services, while also protecting vulnerable users' data and thereby bridging the accessibility gap to ensure that the benefits of digital mobility extend to all users, including those most at risk of exclusion.
The complexity of addressing equity in COVID-19-related global health governance and population health research priorities in Canada: a multilevel qualitative study
Authors: Mac-Seing Muriel , Di Ruggiero Erica
Published: December 2024

Background

Since COVID-19 emerged in 2020, the promotion of health equity, including in research, has further been challenged worldwide by both global health governance (GHG) processes and decisions, and national public health control measures. These global and national decisions have also led to the ‘covidization’ of health research agendas where resources have been massively channelled to address COVID-19, especially during the first years of the pandemic. This situation could potentially result in current and future population health research priorities not explicitly tackling equity as a central tenet. The study objective examined how and to what extent the COVID-19-related GHG architecture is affecting population health research priorities in Canada.

Methods

We conducted a multilevel qualitative study informed by the intersectionality-based policy analysis and multiple streams frameworks. We collected and thematically analysed data from four groups of respondents (n = 35: researchers, research funders and global and public health research institutes in Canada, and WHO/international actors) and an interactive feedback workshop (n = 40 participants).

Results

Study findings generated four main themes. First, both global and national COVID-19 responses failed to address equity considerations, especially among populations in situations of vulnerability and marginalisation. Second, the integrated examination of funding, equity, and accountability was judged as necessary determinants of GHG and population health research priorities in Canada. Third, contrary to common beliefs about COVID-19, the consequences were not all negative, but they were also positive and unintended, and lessons can be learned. Fourth, study respondents proposed multiple recommendations to address inequities in the complex intersection between COVID-19-related GHG and population health research in Canada.

Conclusion

This study provides substantial evidence of the multilayered and complex intersection between COVID-19-related GHG and population health research priorities in Canada. Although the window of opportunity was slim according to study respondents, there was still a unique collective effort to address COVID-19-related socioeconomic and health inequities by considering the numerous recommendations proposed by the four groups of study respondents. These recommendations can directly contribute to improving knowledge of global and national population health and equity research strategies in the context of an evolving pandemic and for policy- and decision-makers to adjust and rectify the course of global and public health governance.
The effect of life skills training on reducing domestic violence and improving treatment adherence in women with diabetes experiencing intimate partner violence: a randomized clinical trial based on the theory of self-efficacy
Authors: Rezaee Shahrbanoo , Bagherzadeh Razieh , Reisi Mahnoush , Fotovat Leila , Vahedparast Hakimeh
Published: December 2024

Background

Intimate partner violence (IPV) is a global health problem and the cause of chronic diseases, such as diabetes. It has a negative effect on adherence to treatment, decreases self-efficacy beliefs, and intensifies stress in women. Therefore, this study aimed to investigate the effect of life skills training based on the self-efficacy theory on IPV and adherence to treatment in women with type 2 diabetes.

Methods

This trial was conducted using a pretest-posttest design and follow-up after one month. The samples included 100 women selected by convenience sampling with random block allocation with type 2 diabetes and IPV. The intervention consisted of 8 sessions over one month of life skills training based on self-efficacy theory. Participants completed questionnaires at pre-test, post-test and follow-up, including a demographic information form and questionnaires on IPV and treatment adherence. Considered statistically significant at P < 0. 05.

Results

The mean changes in IPV scores from the pre-test to the post-test were − 8.38 ± 4.06 and − 0.06 ± 3.09 in the intervention and control groups, respectively. Also, the reduction in the intervention group was significantly more than in the control group (P < 0.001; 95%CI=-9.75; -6.89). The mean changes in IPV scores from post-test to follow-up were − 1.36 ± 3.47 and 1.50 ± 4.14 in intervention and control groups, respectively, indicating a statistically significant difference between the two groups (P < 0.001; 95%CI=-4.38; -1.34). The mean changes in adherence scores from the pre-test to the post-test were 11.40 ± 4.23 and 0.68 ± 3.49 in the intervention and control groups, respectively. The increase was significantly higher in the intervention group than in the control group (P < 0.001; 95%CI = 9.18; 12.26). The mean changes in adherence scores from post-test to follow-up were 2.68 ± 5.06 and − 0.86 ± 2.43 in the intervention and control groups, respectively. The difference between the two groups was statistically significant (P < 0.001; 95%CI = 1.95; 5.12).

Conclusion

Life skills training based on self-efficacy theory reduced IPV and improved treatment compliance in women with diabetes under IPV. It is recommended that this training be taught to other patients with chronic conditions as a means of violence prevention and treatment adherence.

Trial registration

The trial was registered with the Iranian Registry of Clinical Trials (IRCT) on 13 October 2022 and can be found on the Iranian Registry of Clinical Trials platform. IRCT registration number: IRCT20090522001930N6.
Information access and COVID-19 vaccination hesitancy among foreign-born persons in Sweden – a focus group interview-study
Authors: Söderberg Mia , Swaid Juhaina , Aurelius Kristina , Rosengren Annika , Jakobsson Kristina , Magnusson Maria
Published: December 2024

Background

In most countries, lower rates of COVID-19 vaccination have been observed in foreign-born individuals, yet little is known about the underlying reasons, especially as reported by these individuals themselves. This exploratory interview study investigated lack of information access and hesitancy towards taking the COVID-19 vaccine among foreign-born individuals in Sweden.

Methods

We used purposive sampling to recruit foreign-born adults who expressed being hesitant towards getting vaccinated, as well as health guides and doulas who were assigned to spread COVID-19 related information in immigrant-dense urban areas. Data were collected using semi-structured focus group interviews, which were transcribed verbatim and analysed according to systematic text condensation.

Results

Three focus group interviews were conducted with altogether eleven participants. One group consisted of health guides/doulas, while the participants in the other groups were gainfully employed in other jobs, or full-time students, or housewives. Four main themes emerged: (1) Language barriers and sociocultural differences, (2) Consequences of not using official Swedish information, (3) Decision-making on COVID-19 vaccination, and (4) Suggestions to improve information dissemination. The lack of information in other languages than Swedish and lack of effective information channels resulted in that most participants barely used information from official Swedish health care and public health institutions. Instead, they relied on social media, social contacts and international media, through which contradictive and negative information about the vaccine was spread. The decision to get vaccinated or not became a process fraught with insecurities about the effectiveness and side effects of the vaccine, which was balanced against wishing to be protected and to contribute to the battle against COVID-19. The participants suggested that information dissemination could be improved by producing a multilingual information outreach and to increase the use of transmission through social interaction with trusted persons and platforms.

Conclusions

An inadequately adapted information strategy prevented some members of the society from making fact-based decisions about getting vaccinated. Several suggestions for improving dissemination were brought forth that can be tested in future communication strategies.
General practitioners’ attitudes and practices regarding sick leave certification for patients with depression in Norway – a cross-sectional study
Authors: Hetlevik Øystein , Ruths Sabine , Grung Ina , Nilsen Stein , Bringedal Berit
Published: December 2024

Background

Depression is among the most frequent reasons for sick leave, whereas health authorities recommend a rather strict practice, arguing that work is health-promoting. We aimed to explore GPs’ attitudes and practices regarding sick leave certification for depressed patients.

Methods

A cross-sectional study using the Norwegian Physician Survey (N = 1617, 70% response rate) in 2021. The GPs in the panel (N = 221) responded to questions about sick leave certification and cooperation with employers and the Norwegian Labour and Welfare Administration (Norwegian acronym: Nav) regarding patients with depression. We used crosstabulation with chi square statistics and logistic regression models to assess differences among GPs.

Results

Among 221 GPs, 62% often/very often perceived patients’ questions for sick leave certification as the main reason for encountering. A total of 46% often/very often considered patients’ expectations inappropriate, with female GPs more frequently than male GPs (36% vs 56%, p = 0.005) and younger GPs more frequently than their older counterparts (p < 0.001). Although 68% considered sick leave as part of treatment, only 16% often/very often initiated sick leave unless patients raised the question. Sixty-seven percent of GPs reported to often/very often avoid sick listing, if possible, more females than males. GPs who often/very often considered questions for sick leave inappropriate less often considered sick leave as part of treatment (odds ratio (OR): 0.25; 95% CI: 0.13–0.49), and less often report a well-functioning cooperation with Nav (OR:0.37; 95% CI:0.14–0.96). GPs who often/very often considered sick leave as part of treatment more often proposed sick leave for their patients (OR:4.70; 96% CI 1.57–14.01) and reported a less strict approach to sick listing (OR: 40; 95% CI: 0.20–0.79). Ninety-five percent of the GPs rarely/never had direct contact with patients’ employers, whereas 92% often/very often asked patients about their dialogue with the workplace. Eighty-eight percent of the GPs often/very often experienced cooperation with NAV as good, and 87% often/very often felt trusted by them.

Conclusions

Most GPs reported a strict attitude towards sick leave for depression, whereas one-third had a less strict approach. Different perceptions of the appropriateness of sick listing indicate variations in treatment and access to social security benefits.
Managing conflict styles to accelerate leadership effectiveness
Authors: Pennington Greg
Published: December 2024

When describing leadership effectiveness as influencing and impacting the feelings, thoughts and behaviors of others, it can be seen as a critical skill in the overall effectiveness of leaders in general, including those in higher education. Understanding what leadership skills contribute to differentiating between average leaders and more effective leaders, provides insights into where transitions from individual academic roles to leadership ones can be accelerated. In this article we share thoughts and an approach to identifying the importance of conflict management as a key leadership skill to increasing overall leadership effectiveness. We describe a workshop facilitated as a component of the Accomplishing Career Transitions (ACT) Program of the American Society for Cell Biology (ASCB). The workshop, A Leadership Primer uses the Thomas-Kilmann Instrument (TKI), individual reflection, peer coaching and goal setting to provide insight into the origin and impact of individual conflict management styles. While there is evidence indicating that the use of a Collaborative style provides more opportunities for effective leadership, the participants in the ACT were like other academic leader samples that showed more use of a Compromising style. The workshop and follow up sessions provided coaching support to identify origins of conflict styles and options for increasing flexibility to apply a range of conflict styles.
Cranial ultrasonographic findings in newborns exposed to SARS-CoV-2: a single-centre cross-sectional analysis
Authors: Scalia Bruna , Saporito Marco Andrea Nicola , Mauceri Laura , Saporito Alessandro Valerio , Privitera Grete Francesca , Ruggieri Martino , Falsaperla Raffaele
Published: December 2024

Background

SARS-CoV-2’s potential consequences on the developing brain are still unknown. The aim of this study was to describe cranial ultrasonographic (cUS) findings in a population of newborns exposed to SARS-CoV-2 born at San Marco Hospital in Catania.

Methods

Two cohort of newborns, one exposed to SARS-CoV-2 both during gestation and at birth and one unexposed, were enrolled in this cross-sectional study conducted according to the STROBE guidelines (Strenghtening the Reporting of Observational Studies in Epidemiology) and underwent cUS. We performed a statistical analysis using the Fisher’s exact test to assess whether significant differences among the two groups existed.

Results

we enrolled 139 exposed newborns (62 females, 77 males with median gestational age 38.4 ± 1.9 W and median weight at birth 3142.8 ± 594.4 g) and 139 unexposed newborns (60 females, 79 males with median gestational age 38,9 ± 1.3 W and median weight at birth 3230 ± 336 g). cUS abnormalities were found in 32 exposed patients (23%) and in 23 (16.5%) unexposed patients. A statistically significant difference was found in the incidence of minor intracranial abnormalities (p 0.036) between exposed and unexposed patients and between newborns exposed during pregnancy and unexposed patients (p 0.016).

Conclusions

in our experience, the incidence of minor intracranial abnormalities was higher in SARS-COV-2-exposed newborns. Our results must be taken with caution and need further confirmation in larger studies but suggest to consider performing cUS at birth in newborns exposed to SARS-CoV-2 in research contexts.
Increased spatial coupling of integrin and collagen IV in the immunoresistant clear-cell renal-cell carcinoma tumor microenvironment
Authors: Soupir Alex C. , Hayes Mitchell T. , Peak Taylor C. , Ospina Oscar , Chakiryan Nicholas H. , Berglund Anders E. , Stewart Paul A. , Nguyen Jonathan , Segura Carlos Moran , Francis Natasha L. , Echevarria Paola M. Ramos , Chahoud Jad , Li Roger , Tsai Kenneth Y. , Balasi Jodi A. , Peres Yamila Caraballo , Dhillon Jasreman , Martinez Lindsey A. , Gloria Warren E. , Schurman Nathan , Kim Sean , Gregory Mark , Mulé James , Fridley Brooke L. , Manley Brandon J.
Published: December 2024

Background

Immunotherapy has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with immunotherapy naïve and exposed primary ccRCC tumors to better understand immunotherapy resistance.

Results

Spatial molecular imaging of tumor and adjacent stroma samples from 21 tumors suggests that viable tumors following immunotherapy harbor more stromal CD8 + T cells and neutrophils than immunotherapy naïve tumors. YES1 is significantly upregulated in immunotherapy exposed tumor cells. Spatial GSEA shows that the epithelial-mesenchymal transition pathway is spatially enriched and the associated ligand-receptor transcript pair COL4A1-ITGAV has significantly higher autocorrelation in the stroma after exposure to immunotherapy. More integrin αV + cells are observed in immunotherapy exposed stroma on multiplex immunofluorescence validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of both COL4A1 and ITGAV. Assessing bulk RNA expression and proteomic correlates in CPTAC databases reveals that collagen IV protein is more abundant in advanced stages of disease.

Conclusions

Spatial transcriptomics of samples of 3 patient cohorts with cRCC tumors indicates that COL4A1 and ITGAV are more autocorrelated in immunotherapy-exposed stroma compared to immunotherapy-naïve tumors, with high expression among fibroblasts, tumor cells, and endothelium. Further research is needed to understand changes in the ccRCC tumor immune microenvironment and explore potential therapeutic role of integrin after immunotherapy treatment.
Pre-vaccination carriage prevalence of Streptococcus pneumoniae serotypes among internally displaced people in Somaliland: a cross-sectional study
Authors: van Zandvoort Kevin , Hassan Abdirahman Ibrahim , Bobe Mohamed Omer , Pell Casey L. , Ahmed Mohamed Saed , Ortika Belinda D. , Ibrahim Saed , Abdi Mohamed Ismail , Karim Mustapha A. , Eggo Rosalind M. , Ali Saleban Yousuf , Hinds Jason , Soleman Saeed Mohamood , Cummings Rachael , McGowan Catherine R. , Mulholland E. Kim , Hergeye Mohamed Abdi , Satzke Catherine , Checchi Francesco , Flasche Stefan
Published: December 2024

Background

Populations affected by humanitarian crises likely experience high burdens of pneumococcal disease. Streptococcus pneumoniae carriage estimates are essential to understand pneumococcal transmission dynamics and the potential impact of pneumococcal conjugate vaccines (PCV). Over 100 million people are forcibly displaced worldwide, yet here we present only the second pneumococcal carriage estimates for a displaced population.

Methods

In October 2019, we conducted a cross-sectional survey among internally displaced people (IDP) living in Digaale, a permanent IDP camp in Somaliland where PCV has not been implemented. We collected nasopharyngeal swab samples from 453 residents which were assessed for presence of pneumococci and serotyped using DNA microarray.

Results

We found that pneumococcal carriage prevalence was 36% (95%CI 31–40) in all ages, and 70% (95%CI 64–76) in children under 5. The three most common serotypes were vaccine serotypes 6B, 19F, and 23F. We estimated that the serotypes included in the 10-valent PNEUMOSIL vaccine were carried by 41% (95%CI 33–49) of all pneumococcal carriers and extrapolated that they caused 52% (95%CI 35–70) of invasive pneumococcal disease. We found some evidence that pneumococcal carriage was associated with recent respiratory symptoms, the total number of physical contacts made, and with malnutrition in children under 5. Through linking with a nested contact survey we projected that pneumococcal exposure of children under 2 was predominantly due to contact with children aged 2–5 (39%; 95%CI 31–48) and 6–14 (25%; 95%CI 17–34).

Conclusions

These findings suggest considerable potential for direct and indirect protection against pneumococcal disease in Digaale through PCV use in children and potentially adolescents.
Can Massive Technological Progress Hurt Workers? A Review of Power and Progress by Daron Acemoglu and Simon Johnson
Authors: Morton Fiona Scott
Published: December 2024

This book offers a radical thesis: Technological innovation often benefits elites while worsening conditions for workers, challenging the common view that technology always improves living standards. Through historical transitions like the Industrial Revolution, the authors illustrate how innovations have frequently led to worker exploitation. They argue that governance, rather than competition, determines whether technological advances benefit society. In the digital age, platforms exploit user data without fair compensation, causing harm through addictive services and poor regulation. The book calls for stronger regulations to protect consumers and ensure that innovation aligns with societal well-being, especially as artificial intelligence spreads. (JEL D72, J80, N30, N40, N70, O31, O33)
Sources on the history of Premonstratensian nunneries in medieval Bohemia in Czech archives and libraries
Authors: Pátková Hana , Hradilová Marta
Published: December 2024

The dissolution of the female Premonstratensian convents of Doksany and Chotěšov in Bohemia during the reforms of Joseph II at the end of the eighteenth century had a direct impact on the preservation of the sources of their history. Now, they are scattered in more places, both archives and libraries. This paper aims to draw attention to the institutions and fonds where these sources are deposited today.
waves of flickering murmurs in everyday life: playing between ages
Authors: Haynes Joanna , Costa carvalho Magda , Johansson Viktor , Almeida Tiago , Peach Lois , Wickett Karen , Blandon Claudia , Bush Emma , Wolf Arthur c. , Petropoulos Georgios , Reynolds Rose-anne , Caetano-silva Giovanna , Paal Kathrin , Khosa Bakhtawar , Hannam Patricia , Oester-barkey Hanna , Landau Dani , Andrews Mandy , Georgeson Jan
Published: December 2024

The article explores the rich and varied experiences of a collective writing project, unfolding through an anecdote involving Charlie, a young boy who creatively disrupted conventional photography methods. This incident, during an evening promenade by the sea in Ericeira (Portugal), epitomizes the project's embrace of playfulness and exploration of diverse perspectives–materialized through Charlie's playful insistence on experimenting with different angles. The event embodied the group’s approach to writing, leading to a collective inquiry into the interplay of ages, angles, and other themes like waves, threads, shadows, and liminal spaces. The project, driven by the Between Ages Collective, began with informal gatherings in Plymouth, UK, and expanded into a year-long online reading group. Participants, spanning different generations and academic stages, shared various materials, including films, picture books, and scholarly texts, which inspired individual contributions. Influenced by the Collective's collaborative spirit, these contributions explore the concept of 'between ages' – a metaphorical and literal space of transition and fluidity. Contributors were invited to craft pieces that delve into the 'between ages' theme, often exploring serendipitous moments that transform interactions and experiences. The writing tries to capture a sense of openness and curiosity, embracing the uncertainties and ambiguities inherent in the process. The works do not strictly adhere to conventional academic or narrative forms but rather emerge from the collective's shared experiences, including cooking, eating, swimming and walking together. The article suggests that these writings are not meant to be definitive or conclusive but are explorations that invite readers to engage with the mundane and profound textures of everyday life. The stories and themes explored are marked by their diversity in style, rhythm, and imagery, ranging from reflections on the philosophy of shadows to the profound implications of intergenerational and interspecies relationships. The Collective’s work is presented as an ongoing experiment in thinking and writing together, with each piece offering unique insights into the fluid and often blurred boundaries between different states of being. This openness to the in-between spaces brings into question the notion of fixed identities and experiences, inviting a more nuanced understanding of the relational dynamics that shape existence. The article allows the readers to delve into these narratives and engage with the myriad ways they resonate with broader themes of being, storying, and connecting.
Leveraging Critical Diversity Literacy (CDL) to Promote Social Justice through Reflexive Research in Higher Education
Authors: Vanyoro Kudzaiishe Peter , Steyn Melissa
Published: December 2024

Critical Diversity Literacy (CDL) is a lens we can use to achieve social justice consciousness among privileged identities in academic spaces. CDL, by Melissa Steyn (2014), consists of ten criteria that reveal how and why specific differences make a difference. Among other things, CDL exposes the workings of power through structures and individual complicity within structures. CDL is about having the capacity to read the complexities of the twenty-first-century world. The article argues that CDL nurtures the development of “critique towards” normalised quotidian language and personal prejudices in research in higher education. Critiquing and interrogating our positionality comes with the literacy of social, political and economic scenarios that play out in our practices. Using the intersections of race, gender, and disability, the article shows how researchers can use Steyn’s ten CDL criteria to acknowledge differences in research in higher education. In this article, the researchers argue that the university, its curriculum, pedagogy, and research methods are contested cultural terrains. The article illustrates how CDL can challenge some limitations of traditional research methods in creating positive social justice outcomes.
Multispectral imaging through scattering media and around corners via spectral component separation
Authors: Wei Yi , Zhao Yan , Liu Lingfeng , Hu Jinfei , Bai Lianfa , Guo Enlai , Han Jing
Published: December 2024

Existing methods for imaging through scattering media prioritize grayscale and often falter in resolving multispectral speckles, leading to inadequate spectral recovery. We propose a method that establishes a spectral component separation model for high-quality multispectral imaging through scattering media and around corners. By leveraging the uncorrelation among speckles of different wavelengths and the superposition essence of multispectral speckles, a multispectral speckle simplex with speckles of different wavelengths as vertices is constructed. To resolve these vertices, spectral intensity modulation and a joint-solving mechanism are designed for mutual cooperation. This mechanism employs the Harsanyi-Farrand-Chang method for wavelength number estimation, enhances vertex component analysis with a standby rule for initial solutions, and implements an improved non-negative matrix factorization algorithm for accurate separation. Our method successfully recovers multispectral objects from separated speckles, as confirmed by experiments across six wavelength channels. It is also validated for imaging hidden objects around corners, enhancing surround view functionality. This technique holds significant promise for multispectral imaging in various scattering environments.
Multiplexed wavefront sensing using a grating array-based wavefront sensor
Authors: Singh Jaspal , Pathak Biswajit , Narayanamurthy C. S. , Ganesan A. R.
Published: December 2024

This paper addresses the ambiguity problem associated with a periodic array of spots in the Shack-Hartmann wavefront sensor (SHWS) when used for multiplexed wavefront sensing, corresponding to multiple isoplanatic patches. We overcome this issue by introducing a multiplexed wavefront sensing scheme, utilizing a grating array-based wavefront sensor that is a programmable version of SHWS. Three beams representing lights from three distinct guide stars are generated to validate the proposed scheme. Each beam passed through different regions of a pseudo-random phase plate, resulting in different random phases that mimic turbulence effects. We detected three wavefronts from a single frame of data by employing a binary phase grating array on a spatial light modulator at the pupil plane. The proposed sensing scheme is compatible with existing wavefront reconstruction algorithms. This study has potential applications in multi-conjugate adaptive optics, where multiple wavefront sensors are needed to detect various isoplanatic patches in order to expand the field of view in turbulent conditions.
Can the speed of information dissemination exceed the speed of light?
Authors: Wan Chuyi
Published: December 2024

In the double-slit interference experiment with light, once one of the slits is instantaneously closed, the point H on the screen directly opposite the other slit will experience a change in the intensity of light at that point. Moreover, the time it takes for the intensity of light at point H to change after the slit is closed is shorter than the time it takes for light from the slit to reach point H. This indicates that information is transmitted from the slit to point H on the screen at a speed faster than the speed of light c. This does not violate Relativity, as it does not conflict with the Principle of Constancy of Light Velocity. Information is transmitted at varying speeds within the wave packet. In the direction parallel to the propagation of the photons, the speed of information transmission matches c. However, in other directions, the speed of information transmission can exceed c. And according to the inference, it appears that causality is not an immutable law of nature. Causality is not easily overturned at the macro level, while it is not so at the quantum level. The law of causality varies under different inertial or non-inertial reference frames. In one reference frame, the cause leads to the result; in another reference frame, the result may leads back to the cause. Cause and result are mutually causal in different reference frames.
Interventions to address empathy-based stress in mental health workers: A scoping review and research agenda
Authors: May Hannah , Millar Josie , Griffith Emma , Gillmore Chris , Kristoffersen Mhairi , Robinson Ross , West Michael
Published: December 2024

Consistently engaging with client distress can negatively impact mental health workers (MHWs). This has been described by the concept of empathy-based stress (EBS) (which encompasses burnout; secondary traumatic stress; compassion fatigue and vicarious trauma). Previous reviews of interventions to reduce EBS have not addressed MHWs as a distinct group, despite evidence suggesting they are particularly vulnerable to it. In the context of rising demand for mental health services, it is especially important to understand how to mitigate the impact of EBS on MHWS. This scoping review therefore aimed to identify and describe available interventions to reduce or prevent EBS in MHWs. A systematic scoping review of the literature between 1970 and 2022 was undertaken using five electronic databases. A total of 51 studies were included, which varied significantly with regards to: interventions used; study methodology and theoretical underpinnings. Studies were grouped according to the level at which they aimed to intervene, namely: individual; team or organisational. The review concluded that most studies intervened at the level of the individual, despite the proposed causes of EBS being predominantly organisational. Furthermore, theoretical links to the origins of EBS were largely unclear. This suggests a lack of empirical evidence from which organisations employing MHWs can draw, to meaningfully prevent or reduce EBS in their staff. A dedicated research agenda is outlined to address this, and, other pertinent issues in the field and signifies a call for more theoretically grounded research.
Quantum game strategy solution for R&D cartel: Reorganizing government R&D investment strategy in Korea
Authors: Won Dongkyu , Lim Jongyeon , Lee BangRae
Published: December 2024

This study reevaluates criticism of the Korean government’s R&D investment strategy, which was considered an ’R&D cartel’ and was cited as a reason for the Korean government’s R&D cuts in 2023, through an advanced framework of quantum game theory. By modeling the interaction between the government and researchers as a quantum information strategy game, it redefines the dynamics of R&D investment as a quantum game involving two key players: the R&D manager (Alice) and the research performer (Bob). This quantum game, akin to the Prisoner’s Dilemma but focused on responsibility and sincerity, allows for the exploration of strategic complexities and decision-making dynamics not possible in classical models. It introduces quantum entanglement and superposition as innovative strategies to shift the paradigm of R&D investment, suggesting that terms like ’R&D bureaucracy’ and ’R&D monopoly’ more accurately describe the moral hazards in this sector than ’R&D cartel’. Through simulations, the paper demonstrates how quantum strategies can significantly alter outcomes, providing fresh insights and policy alternatives for R&D innovation. This research not only challenges conventional investment frameworks but also proposes a novel approach for achieving Pareto optimal outcomes in government R&D investments, emphasizing the transformative potential of quantum game theory in strategic decision-making and policy development.
A framework for fused deposition modelling process evaluation using multivariate process capability analysis
Authors: Alatefi Moath , Al-Ahmari Abdulrahman M. , AlFaify Abdullah Yahia , Saleh Mustafa
Published: December 2024

The rapid advancement of additive manufacturing (AM) requires researchers to keep up with these advancements by continually improving the AM processes. Improving manufacturing processes involves evaluating the process outputs and their conformity to the required specifications. Process capability indices, calculated using critical quality characteristics (QCs), have long been used in the evaluation process due to their proven effectiveness. AM processes typically involve multi-correlated critical QCs, indicating the need to develop a multivariate process capability index (MPCI) rather than a univariate capability index, which may lead to misleading results. In this regard, this study proposes a general methodological framework for evaluating AM processes using MPCI. The proposed framework starts by identifying the AM process and product design. Fused Deposition Modeling (FDM) is chosen for this investigation. Then, the specification limits associated with critical QCs are established. To ensure that the MPCI assumptions are met, the critical QCs data are examined for normality, stability, and correlation. Additionally, the MPCI is estimated by simulating a large sample using the properties of the collected QCs data and determining the percent of nonconforming (PNC). Furthermore, the FDM process and its capable tolerance limits are then assessed using the proposed MPCI. Finally, the study presents a sensitivity analysis of the FDM process and suggestions for improvement based on the analysis of assignable causes of variation. The results revealed that the considered process mean is shifted for all QCs, and the most variation is associated with part diameter data. Moreover, the process data are not normally distributed, and the proposed transformation algorithm performs well in reducing data skewness. Also, the performance of the FDM process according to different designations of specification limits was estimated. The results showed that the FDM process is incapable of different designs except with very coarse specifications.