bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived problems associated with perioperative blood product preparation
Authors: Smeltz Alan M , Huffman Andrew , Isaak Robert S , An Xinming , Balfanz Gregory
Published: January 2025

Timely blood product preparation is important for patients undergoing surgery with a high risk of blood loss. However, in circumstances where no blood refrigerators exist in the operating room theatre complex, numerous potential problem sources during blood product preparation may lead to delays, and tense interpersonal interactions between anaesthesia and blood bank personnel can ensue. To evaluate this at our institution, an anonymous online survey was sent to anaesthesia providers and blood bank technologists. The primary outcome was to determine what blood preparation time anaesthesia providers believed was reasonable to expect, compared to the institutional standard of 90 min. Of the 75 (36%) anaesthesia providers surveyed, 94.9% considered <90 min was reasonable for blood to be prepared and 79.7% considered <60 min was reasonable. There were 92 (42%) total survey respondents, with 54.8% reporting problems to occur ‘frequently’ or ‘always’. The perceived frequency of 18 different possible problem sources was identified. Overall, the results suggest problems with perioperative blood product preparation occur frequently and the expectations of the anaesthetic team around preparation time and availability of blood products are not met. Many potential problem areas were identified that warrant further investigation into the ongoing efforts to improve workflow and interdisciplinary interactions.
Innovative bioinks for 3D bioprinting: Exploring technological potential and regulatory challenges
Authors: Mathur Vidhi , Agarwal Prachi , Kasturi Meghana , Srinivasan Varadharajan , Seetharam Raviraja N , Vasanthan Kirthanashri S
Published: January 2025

The field of three dimensional (3D) bioprinting has witnessed significant advancements, with bioinks playing a crucial role in enabling the fabrication of complex tissue constructs. This review explores the innovative bioinks that are currently shaping the future of 3D bioprinting, focusing on their composition, functionality, and potential for tissue engineering, drug delivery, and regenerative medicine. The development of bioinks, incorporating natural and synthetic materials, offers unprecedented opportunities for personalized medicine. However, the rapid technological progress raises regulatory challenges regarding safety, standardization, and long-term biocompatibility. This paper addresses these challenges, examining the current regulatory frameworks and the need for updated guidelines to ensure patient safety and product efficacy. By highlighting both the technological potential and regulatory hurdles, this review offers a comprehensive overview of the future landscape of bioinks in bioprinting, emphasizing the necessity for cross-disciplinary collaboration between scientists, clinicians, and regulatory bodies to achieve successful clinical applications.
Comparison of Glenoid Bone Loss After Unidirectional Versus Combined Shoulder Instability in a Military Population
Authors: Yoon Annette H. , Sandler Alexis B. , Scanaliato John P. , Klahs Kyle J. , Hurley Eoghan T. , Tyler John , Parnes Nata
Published: January 2025

Background:

While glenoid bone loss (GBL) after anterior shoulder instability correlates with poor functional outcomes, the specific effects of GBL in posterior and combined-type shoulder instability remain poorly characterized, especially in a high-risk military population.

Purpose/Hypothesis:

The purpose of this study was to compare GBL between unidirectional anterior or posterior instability versus combined-type instability in active-duty servicemembers. It was hypothesized that total GBL and GBL in the direction of instability would be greater in those with combined-type instability compared with unidirectional instability.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Active-duty servicemembers who underwent shoulder stabilization surgery between January 2010 and December 2019 were eligible for inclusion. Patients with multidirectional instability, concomitant rotator cuff tears, osteochondritis dissecans of the glenoid or humeral head, superior labral anterior-posterior tears, biceps pathologies, and humeral avulsion of the glenohumeral ligament were excluded. Patients were grouped according to direction of instability (anterior, posterior, or combined), and patient characteristics, instability characteristics, suture anchor use, and GBL were compared between the 3 cohorts.

Results:

In total, 117 patients met the study inclusion criteria. The mean patient age was 29 years, 89.7% were male, the dominant extremity was involved in 63.2%, 65.8% attributed their injuries to a singular traumatic event, and the mean follow-up was 7.9 years. There was no significant difference regarding patient characteristics, injury mechanism, or follow-up time between the 3 cohorts. As compared with the combined-type instability cohort, mean anterior GBL was greater in the anterior instability cohort (8.00% ± 4.40% vs 4.98% ± 5.26% for combined; P = .012), while mean posterior GBL was greater in the posterior instability cohort (7.44% ± 4.54% vs 4.86% ± 5.69% for combined; P = .024). There was no significant difference in mean total GBL between the combined-type (9.84% ± 7.82%) and either of the unidirectional cohorts (anterior: 8.00% ± 4.40% [ P = .231]; posterior: 7.44% ± 4.54% [ P = .082]).

Conclusion:

GBL in the direction of instability was found to be significantly greater in the unidirectional versus combined-type instability cohorts.
Teaching Beyond the Textbook: Public Health Pedagogical Strategies for a Multicultural Landscape
Authors: Daniels Dennis E. N. , Zorich Shauna C.
Published: January 2025

As the national population grows more demographically and culturally diverse, it is critical that public health and health promotion students are equipped to engage with people from varied demographic and cultural backgrounds. One approach to address this need is the utilization of pedagogical approaches that promote cultural responsiveness and facilitate opportunities to apply course material to a multicultural environment. We posit that pedagogical strategies should apply a multicultural lens to real-life healthcare issues, while simultaneously prioritizing experiential learning. Our recommendation is to utilize the integration of two pedagogical approaches: Gay’s Culturally Responsive Teaching and Kolb’s Experiential Learning approaches to integrate diverse student experiences in course assessments, and to promote cultural responsiveness as an outcome in health promotion courses. This paper will examine the application of the integration of the two frameworks in university level health promotion courses.
Postglobalization or reglobalization? A reply to Victor Roudometof
Authors: Steger Manfred B.
Published: January 2025

As the vitality of the ongoing de/reglobalization debate demonstrates, rethinking globalization in our postglobalization era requires the integration and synthesis of multiple strands of knowledge in a way that does justice to the ever-growing complexity of our globalizing world. While I deeply appreciate Victor Roudometof's urgent call to reappraise globalization conceptually in light of our current ‘postglobalization era’, it is important to point out that such theoretical projects have been underway for some time now. To be sure, these research efforts can and should be strengthened as the current de/globalization debate evolves and broadens.
Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex
Authors: Kim Hyunseong , Hong Jin Young , Jeon Wan-Jin , Kim Hyun , Yeo Changhwan , Lee Junseon , Lee Yoon Jae , Ha In-Hyuk
Published: January 2025

Background

Inflammation is a critical protective response in the body, essential for combating infections and healing injuries. However, chronic inflammation can be harmful and significantly contribute to the development and progression of chronic diseases, with macrophage-mediated responses being central to these processes. This study presents “SBR-Pel,” a new therapeutic blend of Shinbaro tab (SBR), a traditional herbal formula, and pelubiprofen (Pel), a non-steroidal anti-inflammatory drug, and investigated their combined anti-inflammatory effects to create a treatment that both improves efficacy and reduces side effects.

Methods

To this end, we performed both in vitro and in vivo analyses, utilizing a mouse model of inflammation. Viability and cytotoxicity assays, immunohistochemistry, enzyme-linked immunosorbent assays, real-time polymerase chain reaction assays, nociception assays, writhing tests, and blood biochemical analyses were performed.

Results

In vitro, SBR-Pel synergistically reduced the production of nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines. SBR-Pel also significantly attenuated paw edema in vivo in a Complete Freund’s adjuvant-induced inflammation model in adult mice. Furthermore, immunohistochemical analyses showed that treatment with SBR-Pel reduced both the infiltration of CD68+ macrophages and the expression of pro-inflammatory cytokines in inflamed tissues. Additionally, compared with individual treatment alone, SBR-Pel enhanced the expression of anti-inflammatory cytokines CD206, TGF-β, and IL-10, indicating a synergistic effect. Our research demonstrates that SBR-Pel effectively diminishes inflammatory pain by reducing macrophage infiltration and pro-inflammatory cytokine secretion. Additionally, while 1.5 mg/kg of Pel alone increases levels of liver and kidney toxicity markers, such as aspartate aminotransferase, alanine aminotransferase, and creatinine, combining it with SBR at a reduced dosage of 0.5 mg/kg maintains these markers at normal levels.

Conclusions

This combined effect highlights SBR-Pel’s potential as an effective treatment for inflammatory diseases driven by heightened macrophage activity, while also minimizing side effects by reducing the Pel dosage.
Synergistic activity of Pitstop-2 and 1,6-hexanediol in aggressive human lung cancer cells
Authors: Stefanello Sílvio Terra , Mizdal Caren Rigon , da Silva Aline Franzen , Todesca Luca Matteo , Soares Félix Alexandre Antunes , Shahin Victor
Published: January 2025

Metastatic cancer cells undergo metabolic reprogramming, which involves changes in the metabolic fluxes, including endocytosis, nucleocytoplasmic transport, and mitochondrial metabolism, to satisfy their massive demands for energy, cell division, and proliferation compared to normal cells. We have previously demonstrated the ability of two different types of compounds to interfere with linchpins of metabolic reprogramming, Pitstop-2 and 1,6-hexanediol (1,6-HD). 1,6-HD disrupts glycolysis enzymes and mitochondrial function, enhancing reactive oxygen species production and reducing cellular ATP levels, while Pitstop-2 impedes clathrin-mediated endocytosis and small GTPases activity. Besides, both compounds interfere with the integrity of nuclear pore complexes, the gatekeepers for all nucleocytoplasmic transport. Herein, we investigate the possible synergistic effects of both compounds on lowly, highly metastatic, and erlotinib-resistant non-small cell lung cancer. We observe a synergistic cytotoxic effect on erlotinib-resistant cells. Moreover, motility assays show that the compounds combination significantly impedes the motility of all cells. Drug safety and tolerability assessments were validated using the in vivo model organism Caenorhabditis elegans, where fairly high doses showed negligible impact on survival, development, or behavioral parameters. Our findings propose that the 1,6-HD and Pitstop-2 combination may usher in the design of potent strategies for treating advanced lung cancer.
Exploring peer learning module vs. conventional tutorials: effects on engagement and learning outcomes among first-year medical students
Authors: Arasappa Vishwanath Vinay , Raghuramaiah Sindhu , Rasalkar Kavita
Published: January 2025

Background

In contemporary medical education, it is essential to raise student involvement and active participation in the learning process. By contrasting small-group peer learning modules with teacher-led conventional tutorial sessions, we aim to provide insights into their respective influences on learning outcomes and the overall learning experience among 150 first-year medical students.

Methods

Each group consisted of 50 students. These students were further divided into two groups and a pretest was administered on the day of the session. One group engaged in conventional tutorials, while the other participated in a peer learning module. Post-tests and session feedback were provided after each session.

Results

Results from the posttest revealed advancement in both learning approaches compared to the pretest. Compared to tutorials, the level of progress was much higher following peer learning with a p-value of < 0.05. Participants felt that while the tutorials helped them cover the full subject and saved time, they occasionally got monotonous and there was little active engagement. Students who participated in the peer learning method said that while interaction aided in a better learning experience, improved communication skills, and had more active participation, there was less time for discussion and some group members were reticent and ineffective in explaining the concepts.

Conclusions

The peer learning module is thought to be superior to conventional tutorial classes since it promises active involvement from all students, promotes greater learning, and aids in skill improvement, thus assisting students to help each other in gaining insight into the process of active learning.
How do staff work in NHS hospital operations management meetings to support resilience in everyday service delivery? A qualitative study
Authors: Sutton L. , Tarrant C. , Willars J. , Coats T. , Simmonds M. , Mclean D. , Boyle A. , Dreesbeimdiek K. , Richter S. , Oyedijo A. , Roland D.
Published: January 2025

Background

Operations Management meetings in NHS hospitals provide an opportunity for operational and clinical staff to monitor demand and capacity and manage patient flow. These meetings play an important role in the achievement of resilient performance over time. However, little is known about the work that takes place within these meetings in the United Kingdom’s National Health Service.

Methods

We conducted a qualitative study observing 29 Operations Management meetings across three English hospitals between June and October 2023. The observations focused on: who was present; how meetings were organised and conducted; what data were used; how decision-making took place; and the types of work that were undertaken. We also conducted 17 semi-structured interviews with divisional leads and meeting chairs. A grounded theory analytic approach involved exploring the data in two sites to identify key themes, and then testing these themes through a third comparator site.

Results

We identified the type and extent of work that took place in these meetings to maintain flow and enable resilient service delivery. Operations Management meetings provided an opportunity for staff to come together to engage in collective sense-making, to develop a shared mental model of the state of the hospital and to build a collective understanding of where action was needed. Review of centralised data, formally encoded and recorded in numerical form, played an important role, but staff also drew on local intelligence to make sense of and adapt to often pressurised situations. We identified three types of work: Sense-making and Interpretation, and Risk work (which together contributed to maintaining organisational function) and Maintaining morale (which supported individual staff resilience).

Conclusions

The work that went on in Operations Management meetings functioned to support organisational and individual resilience, through staff repeatedly sharing and assessing information on capacity and demand, taking action to address these continually changing pressures, and having their efforts recognised.
Advances in nucleic acid-based cancer vaccines
Authors: Liao Hung-Chun , Liu Shih-Jen
Published: January 2025

Nucleic acid vaccines have emerged as crucial advancements in vaccine technology, particularly highlighted by the global response to the COVID-19 pandemic. The widespread administration of mRNA vaccines against COVID-19 to billions globally marks a significant milestone. Furthermore, the approval of an mRNA vaccine for Respiratory Syncytial Virus (RSV) this year underscores the versatility of this technology. In oncology, the combination of mRNA vaccine encoding neoantigens and immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in eliciting protective responses against diseases like melanoma and pancreatic cancer. Although the use of a COVID-19 DNA vaccine has been limited to India, the inherent stability at room temperature and cost-effectiveness of DNA vaccines present a viable option that could benefit developing countries. These advantages may help DNA vaccines address some of the challenges associated with mRNA vaccines. Currently, several trials are exploring the use of DNA-encoded neoantigens in combination with ICIs across various cancer types. These studies highlight the promising role of nucleic acid-based vaccines as the next generation of immunotherapeutic agents in cancer treatment. This review will delve into the recent advancements and current developmental status of both mRNA and DNA-based cancer vaccines.
Association of high complement and low immunoglobulins with the clinical symptoms of patients with fibromyalgia
Authors: Izuno Satoshi , Hosoi Masako , Anno Kozo , Kato Takahiro A. , Sudo Nobuyuki , Yoshihara Kazufumi
Published: January 2025

Background

Fibromyalgia (FM) is a disease characterized by chronic widespread pain concomitant with various symptoms such as fatigue and anxiety. Although chronic inflammation has been implicated in the immunological abnormalities of FM, there are few human studies on complement and immunoglobulins. In this study, we investigated the immunological characteristics of FM patients and the association between their clinical symptoms and immunological indices, including complement and immunoglobulins.

Methods

1) The serum 50% hemolytic complement activity (CH50), C3, C4, IgG, IgM, and hsCRP of 36 FM patients and 30 healthy sex- and age-matched controls (HC) were measured and compared. 2) Data from the Brief Pain Inventory (pain intention and pain interference subscales), the visual analog scale (VAS) (low back pain, knee pain, and fatigue), the State-Trait Anxiety Inventory and the Center for Epidemiologic Studies Depression Scale (anxiety and depression), and CH50, IgG, and hsCRP as immunological indices were acquired for 41 FM patients. Correlation analysis was done of the clinical symptom and immunological indices.

Results

1) The FM group had significantly higher CH50 and lower IgG and IgM than the HC group after adjusting for body mass index (BMI). 2) Correlation analysis of immunological indices and clinical symptoms showed a positive, partial correlation between CH50 and fatigue and trait anxiety after adjusting for sex, age, and BMI.

Conclusions

FM patients had higher CH50 and lower immunoglobulin levels than HCs. CH50 was also associated with the fatigue and trait anxiety of FM patients. Further studies are needed to determine whether changes in these immunological indices can be used as biomarkers and/or therapeutic targets for FM.
Examining the integration of refugees into the national health system in Uganda: an analysis using the policy triangle framework
Authors: Komakech Henry , Elnakib Shatha , Karroum Lama Bou , Nyachwo Evelyn , Adoch Winnie , Sali Sarah , Okeny Godfrey Goddie , Orach Christopher Garimoi
Published: January 2025

Background

Uganda has been confronted with a sustained influx of refugees for decades. This prompted the government to explore opportunities to integrate refugees into local service structures including its national health system. This paper chronicles the history of policies and strategies that have influenced the integration of refugees into the national health system in Uganda and investigates factors that impacted policy evolution and progression.

Methods

We used a case study approach that drew on a document review and key informant interviews with 28 respondents at national and subnational levels. Interviews were analyzed using thematic qualitative analysis and findings were organized using Walt and Gilson’s Policy Triangle Framework. Data from the literature review, media review, and key informant interviews were triangulated.

Results

Uganda’s experience with the integration of refugee’s dates to 1999 when the country first implemented the Self-reliance strategy. Since then, policy learning and evolution have taken place, with policies around integration evolving and improving over time, moving the country towards more effective implementation of integrated health services. A conducive policy environment was key as a set of legislations at national and district-levels and sector-specific plans and budgets that included refugees have provided the foundation for implementation. The integration received support and buy-in from the highest levels of government including the President and the Office of The Prime Minister. This was coupled with deliberate efforts by the government to mainstream refugee response in local plans and budgets, allowing implementation at district and sub-district levels. These factors were pivotal to the implementation of the integration agenda.

Conclusion

Our study highlights the complex, dynamic, evolving, and multifaceted nature of the multisectoral health policy process in the integration of health services in refugee settings. The findings shed light on the importance of collaboration between stakeholders, mobilization of legal and political frameworks to shape the integration of refugee health services into the national health system, and the importance of ensuring that high-level commitments translate to action and development plans at local levels.
TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma
Authors: Guo Hanrui , Wang Meiling , Ni Caiya , Yang Chun , Fu Chunxue , Zhang Xiaoman , Chen Xueling , Wu Xiangwei , Hou Jun , Wang Lianghai
Published: January 2025

Background

Triggering receptor expressed on myeloid cells 2 (TREM2), a surface receptor predominantly expressed on myeloid cells, is a major hub gene in pathology-induced immune signaling. However, its function in hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the role of TREM2 in the tumor microenvironment in the context of HCC progression.

Methods

HCC was experimentally induced in wild-type (WT) and Trem2-deficient (Trem2
−/−) mice, and clinical sample analysis and in vitro studies on macrophages were conducted. HCC cells were treated with conditioned medium from WT or Trem2
−/− macrophages, and their malignant phenotypes and underlying mechanisms were analyzed.

Results

TREM2 deficiency reduced liver tumor burden in orthotopic and subcutaneous HCC models by altering CD8+ T cell infiltration. Trem2-deficient macrophages presented increased chemokine secretion. TGF-β1 was found to be positively correlated with TREM2 expression in HCC, and TGF-β blockade reversed TREM2 induction. On the other hand, TREM2+ macrophages were found to be associated with glycolysis and PKM2 expression in HCC cells; this association may be related to the secretion of IL-1β, which enhances the malignant phenotypes of HCC cells.

Conclusions

These results reveal that TREM2+ macrophages play a driving role in HCC progression by suppressing CD8+ T cell infiltration and promoting tumor cell glycolysis, providing a new therapeutic target for HCC.
Large simple randomized controlled trials—from drugs to medical devices: lessons from recent experience
Authors: Buccheri Sergio , James Stefan , Mafham Marion , Landray Martin , Melvin Tom , Oldgren Jonas , Bulbulia Richard , Bowman Louise , Hoogervorst Lotje Anna , de Mheen Perla J. Marang-van , Juni Peter , McCulloch Peter , Fraser Alan G.
Published: January 2025

Randomized controlled trials (RCTs) are the cornerstone of modern evidence-based medicine. They are considered essential to establish definitive evidence of efficacy and safety for new drugs, and whenever possible they should also be the preferred method for investigating new high-risk medical devices. Well-designed studies robustly inform clinical practice guidelines and decision-making, but administrative obstacles have made it increasingly difficult to conduct informative RCTs. The obstacles are compounded for RCTs of high-risk medical devices by extra costs related to the interventional procedure that is needed to implant the device, challenges with willingness to randomize patients throughout a trial, and difficulties in ensuring proper blinding even with sham procedures. One strategy that may help is to promote the wider use of simpler and more streamlined RCTs using data that are collected routinely during healthcare delivery. Recent large simple RCTs have successfully compared the performance of drugs and of high-risk medical devices, against alternative treatments; they enrolled many patients in a short time, limited costs, and improved efficiency, while also achieving major impact. From a task conducted within the CORE-MD project, we report from our combined experience of designing and conducting large pharmaceutical trials during the COVID-19 pandemic, and of planning and coordinating large registry-based RCTs of cardiovascular devices. We summarize the essential principles and utility of large simple RCTs, likely applicable to all interventions but especially in order to promote their wider adoption to evaluate new medical devices.
Exploring the prevalence of gout among underrepresented low socioeconomic status type 2 diabetes populations
Authors: Smith Jessica , Martin Abey , Mundadan Jane , Roberts Michael , Roman Youssef , Bravo-Nuevo Arturo , Daghigh Farzaneh
Published: January 2025

Background

Underserved and underrepresented populations often lack access to affordable, quality healthcare, educational resources, and nutritious foods, all of which contribute to increased risk of Type 2 Diabetes and gout. Type 2 Diabetes is a condition characterized by the denaturation of the insulin receptors, due to chronically high blood glucose levels, leading to impaired regulation of blood sugar. Gout is a chronic inflammatory disease affecting joints in the lower limbs, marked by elevated serum urate levels and the accumulation of uric acid crystals in synovial fluid, causing painful flare-ups that significantly impact quality of life.

Methods

This multisite cross-sectional study was conducted in three low-income senior residential communities across the mid-Atlantic United States, including Philadelphia and Harrisburg, Pennsylvania, and Clinton, Maryland. A total of 88 consenting participants were surveyed on their health history and tested for hemoglobin A1c (HbA1c), blood glucose, and uric acid levels using finger-stick blood tests and commercially available devices. Inclusion criteria included individuals of any gender, aged 35–92, residing in these communities. Exclusion criteria were a personal history of cancer, organ transplantation, or current pregnancy. Educational materials were provided after discussing each participant’s results.

Results

There is an identifiable prevalence of gout among this population of low-income senior adults living with Type 2 Diabetes. Among the participants, 30.7% had serum urate levels indicative of hyperuricemia, exceeding the national average of 20.1% as reported by the National Health and Nutrition Examination Survey. Participants with high HbA1c had significantly higher uric acid levels compared to those with lower HbA1c levels, with diabetic levels of HbA1c accounting for approximately 40% of the variance in uric acid levels. Additionally, study participants who smoked cigarettes were more likely to have hyperuricemia than non-smokers.

Conclusion

Preventive educational efforts focused on diet and lifestyle are critical to reducing the incidence of gout and Type 2 Diabetes in low-income elderly populations. Diabetic individuals are at a higher risk of developing hyperuricemia and gout compared to non-diabetics. Community-based educational health programs are necessary to make a measurable impact on these populations, prevent disease progression, and reduce the burden on healthcare systems.
StreamChol: a web-based application for predicting cholestasis
Authors: Rodríguez-Belenguer Pablo , Soria-Olivas Emilio , Pastor Manuel
Published: January 2025

This article introduces StreamChol, a software for developing and applying mechanistic models to predict cholestasis. StreamChol is a Streamlit application, usable as a desktop application or web-accessible software when installed on a server using a docker container.

StreamChol allows a seamless integration of pharmacokinetic analyses with Machine Learning models. This integration not only enables cholestasis prediction but also opens avenues for predicting other toxicological endpoints requiring similar integrations. StreamChol's Docker containerization also streamlines deployment across diverse environments, addressing potential compatibility issues. StreamChol is distributed as open-source under GNU GPL v3, reflecting our commitment to open science. Through StreamChol, researchers are offered a potent tool for predictive modelling in toxicology, harnessing its strengths within an intuitive and user-friendly interface, without the need for any programming knowledge.

Scientific contribution This work offers a user-friendly web-based tool for cholestasis prediction and a complete workflow for creating web platforms that require the combination of both programming languages, R and Python.
Saponins enhance the stability and cost-efficiency of human embryonic stem cell culture
Authors: Shi Jingyi , Wu Mei , Fang Shi , Liu Zhuo , Liu Huihui , Zhao Ying , Liu Linlin , Shao Zhicheng
Published: January 2025

The cultivation and differentiation of human embryonic stem cells (hESCs) into organoids are crucial for advancing of new drug development and personalized cell therapies. Despite establishing of chemically defined hESC culture media over the past decade, these media's reliance on growth factors, which are costly and prone to degradation, poses a challenge for sustained and stable cell culture. Here, we introduce an hESC culture system(E6Bs) that facilitates the long-term, genetically stable expansion of hESCs, enabling cells to consistently sustain high levels of pluripotency markers, including NANOG, SOX2, TRA-1–60, and SSEA4, across extended periods. Moreover, organoids derived from hESCs using this medium were successfully established and expanded for at least one month, exhibiting differentiation into cortical organoids, GABAergic precursor organoids and heart-forming organoids. This innovative system offers a robust tool for preserving hESC homeostasis and modeling the nervous system in vitro.
Exposure of Apis mellifera (Hymenoptera: Apidae) colonies to imidacloprid impairs larval development, promotes oxidative stress in pupae, and induces changes in the midgut of adult bees
Authors: Moreira Daiani Rodrigues , de Souza Tuan Henrique Smielevski , Galhardo Douglas , Figueira Cinthia Leão , Baulli Samara Calvi , da Silva Breno Gabriel , das Chagas Francieli , Oliveira José Washington Santos , Rocha Jean Samel , de Souza Khatlab Angélica , Gasparino Eliane , de Alencar Arnaut de Toledo Vagner , Gigliolli Adriana Aparecida Sinópolis , Ruvolo-Takasusuki Maria Claudia Colla
Published: January 2025

Bees are essential pollinators that contribute to maintaining biodiversity and increasing agricultural production. However, by foraging on agricultural crops, bees may become contaminated with compounds used for pest control. In this study, we exposed bee (Apis mellifera L.) colonies to the insecticide imidacloprid (IMD) under field conditions to assess the occurrence of oxidative stress in larvae and pupae and investigate morphological changes in the fat body and midgut of larvae and midgut of adult bees. The apiary area was divided into three groups: control, commercial formulation containing IMD (Evidence® 700WG) (IMDCF), and IMD active ingredient (Sigma–Aldrich) (IMDAI). Treatment groups were fed syrup containing 1 µg L−1 IMD, whereas the control group was fed syrup only. Compared with the control, larvae exposed to IMDCF or IMDAI for 42 days exhibited morphological changes in the external body, midgut, and fat body. The midgut of adult bees contaminated with IMDCF showed only structural remnants of the peritrophic membrane and absence of regenerative cell nests. Oxidative stress analyses revealed that IMDCF-exposed larvae had higher nitrite and carbonylated protein contents and lower catalase and superoxide dismutase activity than control individuals. In pupae, IMDAI decreased catalase activity while increasing superoxide dismutase activity. These findings indicate that IMD has the potential to significantly impact the development of bees and their colonies by disrupting vital organs responsible for normal physiological functioning and overall activities of individuals. Oxidative stress, which was detected at different stages of bee development, may induce lipid, protein, and DNA oxidation, leading to cell death.

Graphical Abstract
Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study
Authors: Jiang Fuchuan , Ahmad Sajjad , kanwal Sadia , Hameed Yasir , Tang Qian
Published: January 2025

Background

Uterine Corpus Endometrial Carcinoma (UCEC) is a prevalent gynecologic malignancy with complex molecular underpinnings. This study identifies key woundhealing genes involved in UCEC and elucidates their roles through a comprehensive analysis.

Methods

In silico and in vitro experiments.

Results

Seventy wound healing-associated genes were extracted from the Gene Ontology (GO) database, and a protein-protein interaction (PPI) network was constructed using the STRING database. CytoHubba analysis in Cytoscape identified six pivotal hub genes: CD44, FGF2, FGF10, KDM6A, FN1, and MMP2. These genes exhibited significantly lower expression in UCEC cell lines compared to normal controls, as confirmed by RT-qPCR. Receiver Operating Characteristic (ROC) analysis demonstrated their potential as diagnostic biomarkers, with Area Under the Curve (AUC) values ranging from 0.94 to 1.00. Validation using TCGA datasets revealed consistent downregulation of these genes in UCEC samples, corroborated by immunohistochemical staining. Promoter methylation analysis showed significantly higher methylation levels in UCEC, correlating with decreased mRNA expression and poor survival outcomes. Genetic alteration analysis indicated frequent mutations in FN1 and KDM6A, although these did not significantly affect survival. Functional analysis using the CancerSEA database highlighted the involvement of these genes in critical cancer-related processes, including angiogenesis, apoptosis, and metastasis. Immune correlation studies revealed significant associations with immune inhibitor genes and distinct expression patterns across immune subtypes. Overexpression studies in UCEC cell lines demonstrated that CD44 and MMP2 reduce proliferative ability while enhancing migration and wound healing.

Conclusion

Collectively, these findings underscore the crucial roles of CD44, FGF2, FGF10, KDM6A, FN1, and MMP2 in UCEC pathogenesis, highlighting their potential as biomarkers and therapeutic targets in this malignancy.
Applying quality improvement to clinical practice: primer for psychiatrists
Authors: Nidumolu Aditya , Waddell Andrea E. , Burra Tara A.
Published: January 2025

Quality improvement (QI) is an evidence-based approach to analysing and improving healthcare systems. QI's success has led it to become a required competency expected of medical professionals in several countries. However, much of the QI literature to date has not focused on mental health. Moreover, many psychiatrists have no formal training in QI. To address this gap, this article introduces key QI concepts, including six dimensions of quality care, the Model for Improvement and plan–do–study–act cycles. Each QI concept is illustrated using a fictitious case study of an out-patient psychiatrist reducing chronic benzodiazepine use in their clinic.
Functional and effective connectivity between reward and inhibitory control networks underlying subclinical binge eating
Authors: Chen Ximei , Li Wei , Luo Yijun , Liu Yong , Xu Xiaofei , Gao Xiao , Chen Hong
Published: January 2025

Background

Knowledge is growing on the essential role of neural circuits involved in aberrant cognitive control and reward sensitivity for the onset and maintenance of binge eating.

Aims

To investigate how the brain's reward (bottom-up) and inhibition control (top-down) systems potentially and dynamically interact to contribute to subclinical binge eating.

Method

Functional magnetic resonance imaging data were acquired from 30 binge eaters and 29 controls while participants performed a food reward Go/NoGo task. Dynamic causal modelling with the parametric empirical Bayes framework, a novel brain connectivity technique, was used to examine between-group differences in the directional influence between reward and executive control regions. We explored the proximal risk factors for binge eating and its neural basis, and assessed the predictive ability of neural indices on future disordered eating and body weight.

Results

The binge eating group relative to controls displayed fewer reward-inhibition undirectional and directional synchronisations (i.e. medial orbitofrontal cortex [mOFC]–superior parietal gyrus [SPG] connectivity, mOFC → SPG excitatory connectivity) during food reward_nogo condition. Trait impulsivity is a key proximal factor that could weaken the mOFC–SPG connectivity and exacerbate binge eating. Crucially, this core mOFC–SPG connectivity successfully predicted binge eating frequency 6 months later.

Conclusions

These findings point to a particularly important role of the bottom-up interactions between cortical reward and frontoparietal control circuits in subclinical binge eating, which offers novel insights into the neural hierarchical mechanisms underlying problematic eating, and may have implications for the early identification of individuals suffering from strong binge eating-associated symptomatology in the general population.
De-Escalation Strategies With Immune Checkpoint Blockers in Non–Small Cell Lung Cancer: Do We Already Have Enough Evidence?
Authors: Remon Jordi , Bortolot Martina , Bironzo Paolo , Cortiula Francesco , Menis Jessica , Brandao Mariana , Naidoo Jarushka , van Geel Robin , Reguart Noemi , Arrieta Oscar , Mountzios Giannis , Hendriks Lizza E.L. , Besse Benjamin
Published: January 2025

Immune checkpoint blockers (ICBs) have revolutionized the treatment of non–small cell lung cancer (NSCLC). Currently, one-dose-fits-all maximalist regimens have been considered the standard of care, with ICBs administered at flat doses regardless of patients’ weight. Treatment duration with ICBs is often arbitrary across stages, ranging from a fixed time point to until disease progression or unacceptable toxicity. However, the pharmacokinetic and pharmacodynamic properties of ICBs differ significantly from those of traditional cytotoxic drugs and the approved and selected doses on the basis of the maximum tolerated dose are often overestimated as there is limited evidence supporting a direct relationship between therapeutic intensity and outcomes. This can lead to overtreatment of patients, resulting in an increased risk of toxicity without enhanced efficacy. In addition, the use of these drugs is associated with significant costs that burden the global health care system and exacerbate disparities in access to care. De-escalating treatment by reducing the dose, duration, and frequency of administration of ICBs could optimize treatment efficacy, reduce toxicities, improve patients' quality of life, and even decrease costs. Ultimately, de-escalation strategies may help to reduce treatment inequalities and to improve drug access worldwide. The aim of this review is to summarize and discuss the main issues and challenges regarding the de-escalation of ICBs in patients with NSCLC, focusing on dose-intensity reduction and treatment duration selection. Moreover, we assess the economic impact of implementing de-escalation approaches.
Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis
Authors: Hawley Joshua , Lea Robert , Biga Veronica , Papalopulu Nancy , Manning Cerys
Published: January 2025

In the developing mouse ventral spinal cord, HES5, a transcription factor downstream of Notch signalling, is expressed as evenly spaced clusters of high HES5-expressing neural progenitor cells along the dorsoventral axis. While Notch signalling requires direct membrane contact for its activation, we have previously shown mathematically that contact needs to extend beyond neighbouring cells for the HES5 pattern to emerge. However, the presence of cellular structures that could enable such long-distance signalling was unclear. Here, we report that cellular protrusions are present all along the apicobasal axis of individual neural progenitor cells. Through live imaging, we show that these protrusions dynamically extend and retract reaching lengths of up to ∼20 µm, enough to extend membrane contact beyond adjacent cells. The Notch ligand DLL1 was found to colocalise with protrusions, further supporting the idea that Notch signalling can be transduced at a distance. The effect of protrusions on the HES5 pattern was tested by reducing the density of protrusions using the CDC42 inhibitor ML141, leading to a tendency to decrease the distance between high HES5 cell clusters. However, this tendency was not significant and leaves an open question about their role in the fine-grained organisation of neurogenesis.
Exposure to sub-optimal temperature during early development decreases hypoxia tolerance in juvenile Fundulus heteroclitus
Authors: Blanchard Tessa S. , Earhart Madison L. , Strowbridge Nicholas , Schulte Patricia M.
Published: January 2025

Cross-protection occurs when exposure to one stressor confers heightened tolerance against a different stressor. Alternatively, exposure to one stressor could result in reduced tolerance against other stressors. Although cross-protection has been documented in a wide range of taxa at juvenile and adult life stages, whether early developmental exposure to a stressor confers cross-protection or reduced tolerance to other stressors later in life through developmental plasticity remains largely unexplored. In this study, we examined whether altered temperature during embryonic development results in developmental plasticity in upper thermal tolerance or hypoxia tolerance using a small topminnow, Fundulus heteroclitus, and examined potential underlying molecular mechanisms. We incubated embryos at one of two ecologically relevant temperatures (20°C or 26°C) until hatch. Once hatched, fish were raised at a common temperature of 20°C for 1 year, and tolerance was assessed in both juveniles (6 months) and early adults (1 year). Developmental temperature had no significant effect on thermal tolerance (CTmax) in juvenile fish, or on the transcript abundance of thermal tolerance-related genes (constitutive heat shock proteins, hsc70, hsp90b). In contrast, reduced developmental temperature decreased hypoxia tolerance but increased transcript levels of the hypoxia inducible factor hif1α in juvenile fish but the effects were less evident in older fish. Overall, we found no indication of developmental plasticity for thermal tolerance, but there was evidence of negative impacts of lower developmental temperature on hypoxia tolerance in juveniles associated with changes in gene expression, providing evidence of developmental plasticity across stressors and levels of organization.
Sublethal changes to coral metabolism in response to deoxygenation
Authors: Mallon J. E. , Altieri A. H. , Cyronak T. , Melendez-Declet C. V. , Paul V. J. , Johnson M. D.
Published: January 2025

Coastal deoxygenation poses a critical threat to tropical coral reefs. Dissolved oxygen (DO) depletion can cause hypoxia-induced stress and mortality in scleractinian corals. Coral hypoxic responses are species-specific and likely modulated by the duration and severity of low-DO conditions, although the physiological mechanisms driving hypoxia tolerance are not fully understood. In this study, the Caribbean corals Acropora cervicornis, Porites astreoides and Siderastrea siderea were exposed to either severe (1.5 mg l−1 DO) or moderate (3.5 mg l−1 DO) deoxygenation or a control treatment (6 mg l−1 DO). All corals survived 2 weeks of deoxygenation but exhibited sublethal changes to coral metabolism after 1- and 2-week exposures, compared with controls. Maximum quantum yield (Fv/Fm) was suppressed after 1 week in both deoxygenation treatments in A. cervicornis, and after 2 weeks in S. siderea and P. astreoides exposed to severe or moderate treatments, respectively. Respiration rates were lower than controls in A. cervicornis and S. siderea after 1 and 2 weeks of severe deoxygenation. The reduced respiration of P. astreoides after 1 week of moderate deoxygenation returned to control levels in week 2. Overall coral metabolic budgets, assessed by ratios of gross photosynthesis to respiration (Pg:R), were more autotrophic, or photosynthesis-dominant, after 1 week of severe deoxygenation in S. siderea and P. astreoides, whereas Pg:R was not significantly different in A. cervicornis between treatments. These results reveal that some corals shift their metabolism to tolerate low-oxygen conditions and avoid bleaching or mortality, indicating that metabolic plasticity is an important aspect of coral resistance to deoxygenation.
Um estudo bibliométrico acerca dos laboratórios de inovação no setor público
Authors: Silva José Roberto Carvalho , Campelo Filho Eulálio Gomes
Published: January 2025

Os laboratórios de inovação constituem um espaço de experimentação com o objetivo principal de promover melhorias em setores considerados críticos na gestão pública. O objetivo desta pesquisa é fazer um levantamento bibliométrico acerca dos laboratórios de inovação no setor público, usando como base de dados a Web of Science e o Portal Periódico da Capes. Para tanto, realizou-se uma análise bibliométrica das publicações disponíveis entre os anos de 2018 a 2024. Dessa forma, desprenderam-se esforços analíticos para o entendimento e a compreensão de quatro pontos centrais: 1) área de concentração do estudo; 2) análise de cocitação; 3) literaturas mais citadas; 4) acoplamento bibliográfico por país. Os resultados encontrados sugerem uma área de pesquisa importante, porém, nascente, havendo a necessidade de mais pesquisas em busca de realidades de aplicação prática dessas ferramentas, assim como estudos para a mensuração dos resultados dos laboratórios de inovação em atividade no setor público.