bluuebunny/crossref_metadata_2025_split huggingface dataset:
The first case of combined pancreatic neuroendocrine tumour and neuroendocrine carcinoma
Authors: Lun Tegan , Rosty Christophe , Palamuthusingam Pranavan 
Published: December 2024

Abstract
Pancreatic neuroendocrine neoplasms are currently thought to originate from distinct progenitor cells that cannot differentiate into each other. We present the first reported case of a combined pancreatic neuroendocrine tumour and neuroendocrine carcinoma in a 58-year-old man who was investigated for abdominal pain and constipation. Imaging revealed a large left upper quadrant mass infiltrating the pancreatic body and tail, splenic hilum, and posterior stomach wall, with five hepatic metastases. This was treated with neoadjuvant and adjuvant chemotherapy, debulking surgery, and lutetium-177-DOTATATE peptide receptor radionuclide therapy. This case emphasises the importance of molecular imaging, meticulous microscopic examination, and multidisciplinary discussion for accurate diagnoses, improved prognostication, and efficacious treatment.
An illustrated description of a modified collagenase Clostridium histolyticum protocol for Peyronie’s disease
Authors: Trost Landon 
Published: December 2024

Abstract

Background
Our team recently published outcomes of a novel technique for the administration of Collagenase Clostridium histolyticum (CCH), which resulted in improved curvature outcomes and reduced number of CCH injections required.

Aim
To provide a detailed and illustrated description of our CCH-administration technique.

Methods
A descriptive summary is provided of the technique, including drug administration, protocol modifications, and post-treatment protocols. Additional details are provided on measurement techniques and disease classification.

Outcomes
Key outcomes include a written and illustrated description of the injection technique and pre-, and postinjection management.

Results
The use of a modified CCH-administration technique has previously been shown to result in mean improvements of 54%–58% in penile curvature while significantly reducing the total number of injections applied. These findings represent the largest improvements published to date. Key aspects of the technique include back-to-back day administration of 0.9 mg suspended in 0.8 mL, application to an ~3 × 1 cm region, inclusion of the dorsal septum (exempting ventral curves), administration during a full erection (day 1), repeat artificial erections with the first injection of each series, in-office modeling (day 2), and post-treatment use of PDE5s and Restorex traction. Appropriate patient counseling on expectations and necessity of complying with all treatment protocols (including post-treatment wrapping) is critical to optimizing outcomes. Common side effects may include ecchymoses, hematomas, blood blisters, impacts on erections and penile sensation, bronzing of the skin, and skin scarring, while more severe complications are rare (&lt;1%).

Clinical Implications
The current manuscript provides a more detailed description of previously published techniques to aid providers in implementation and to mitigate potential adverse events.

Strengths and Limitations
Strengths include reliance on the largest single-team series published on CCH outcomes, rigorous study methodology, prospective/sequential series, and step-wise improvements. Limitations include data obtained from a single center.

Conclusion
The current manuscript provides a detailed narrative and illustrated description of our current CCH-administration technique.
Self-Directed Skills Laboratories Increase Emergency Medicine Physician Confidence in High-Acuity, Low-Opportunity Procedures
Authors: Stuart Sean M , Aubuchon Thomas 
Published: December 2024

ABSTRACT

Introduction
The critical role of emergency physicians in military settings underscores the necessity for a broad and proficient skill set, especially in life-saving procedures such as thoracostomies, endotracheal intubations, and cricothyrotomies, to maintain combat readiness. The current peacetime phase, however, presents challenges in maintaining these skills because of decreased exposure to high-acuity medical scenarios. This decrease in exposure jeopardizes skills retention among military emergency medicine physicians, highlighted by studies showing a significant decline in performance over time because of reduced practice.

Materials and Methods
This study was carried out at the Naval Medical Readiness Training Center Portsmouth under IRB approval, employing a prospective, observational, mixed-methods design. Participants included board-certified emergency medicine physicians engaged in a self-directed, small-group skills lab focusing on central venous catheterization, thoracostomy, intraosseous access, endotracheal intubation, cricothyrotomy, and resuscitative thoracotomy. Pre- and post-lab surveys on a 5-point confidence scale assessed the impact of the lab, with data analyzed via the Wilcoxon signed-rank test to evaluate significant changes.

Results
Fourteen physicians reported pre-lab confidence levels, showing high confidence in central venous catheter access, thoracostomy tube placement, intraosseous catheter placement, and endotracheal intubation. The interventions of cricothyrotomy, resuscitative thoracotomy, and suprapubic catheterization started with notably lower confidence levels. Statistically significant improvements in confidence were observed post-lab for cricothyrotomy, resuscitative thoracotomy, and suprapubic catheterization suggesting the lab’s effectiveness in addressing less frequently practiced procedures.

Conclusions
The Military Health System must find avenues to maintain the clinical skills of wartime procedures in the peacetime environment. Although there is no substitute for clinical encounters, alternative modalities are needed to augment skills retention in high-acuity, low-frequency procedures. Self-directed, small-group task trainers and cadaveric labs are a lower maintenance mechanism by which faculty can improve their confidence in certain procedural skills. Further studies should evaluate if this translates to changes in clinically oriented outcomes and how to optimize such training evolutions within the skills retention paradigm.
Improving Expeditionary Blood Supply via Type-Specific Whole Blood
Authors: Comes Ryan , Olsen Cara , Huang Chih , Carrillo Michael , Patton Seng , April Michael D , Hall Jennifer H , Kulis Peter , Hall Andrew 
Published: December 2024

ABSTRACT

Introduction
Blood is critical to expeditionary casualty care. Currently, low-titer O whole blood is the preferred product, because it serves as a universal blood product, but demand is higher than supply. Type-specific whole blood (TSWB) has the potential to address this shortfall and provide an identical clinical benefit to specific patient populations. This study estimates the benefit of TSWB to the expeditionary blood supply.

Materials and Methods
Potential TSWB demand was estimated based on the product demand during the US involvement in Afghanistan (2001–2021). Potential production yield increases were based on blood production at the Keesler AFB Blood Distribution Center (FY2016–FY2023).

Results
Including type A TSWB is estimated to increase whole blood production 11.1% monthly. Type-specific whole blood, if available, is expected to be utilized in 20.7% to 35.6% of U.S. Military casualties requiring blood transfusion. Seasonality was found in production (P &lt; .001).

Conclusions
Incorporating TSWB is anticipated to meaningfully expand whole blood availability to meet current shortfalls and future expeditionary casualty needs.
Veterans Affairs Military Toxic Exposure Research Conference: Veteran-centric Approach and Community of Practice
Authors: Trembley Janeen H , Barach Paul , Tomáška Julie M , Poole Jedidah T , Ginex Pamela K , Miller Robert F , Sandri Brian J , Szema Anthony M , Gandy Kimberly , Siddharthan Trishul , Kirkness Jason P , Nixon Joshua P , Torres Rosie Lopez , Klein Mark A , Nurkiewicz Timothy R , Butterick Tammy A 
Published: December 2024

ABSTRACT
The U.S. Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act expands benefits and services to U.S. Veterans exposed to military and deployment-related toxicants. Open-air burn pits were used on military bases in the Middle East and Southwest Asia for trash disposal, exposing U.S. troops to numerous and profound health consequences. Research is underway to understand the scope of the health and wellness impacts from burn pit exposures and to establish care standards and meaningfully address the needs of Veterans and military personnel. A virtual plenary conference and a subsequent hybrid in-person/virtual conference were conducted to foster a cross-professional Community of Practice (CoP) approach to address knowledge and implementation gaps in research and clinical care. For the plenary conference, leading experts in Veteran health care advocacy, preclinical, clinical and implementation scientists, clinicians, Veterans, and their families were engaged to present information on the current state of knowledge and solicit feedback from attendees. Often, clinical trials and health care delivery enterprises function as separate entities, with siloed goals, infrastructure, and incentives. Consequently, trials can have less relevance and be less responsive to the needs of Veterans and those responsible for their care. The conference highlighted the need to support Veteran health systems learning, requiring continuous cooperation and a loop of basic and clinical knowledge generation and uptake, and how best to provide care under real-world conditions, not just in determining what interventions work, under what contexts, and also how best to ensure they are provided to Veterans who need them. The in-person/virtual hybrid conference was held to further discuss what was learned from the plenary conference and propose next steps in collaborative efforts to address unmet needs. The purpose of this publication is to disseminate information presented and discussed in the two conferences. Findings are summarized related to centering the Veteran voice and creating a novel, CoP approach for research and health care. U.S. Veteran health care and policy are strengthened and informed by collaborative scientific knowledge, research, and innovation generated by bringing together stakeholders for effective implementation and sustained improvement of Veterans’ health.
The Rich Evolutionary History of the Reactive Oxygen Species Metabolic Arsenal Shapes Its Mechanistic Plasticity at the Onset of Metazoan Regeneration
Authors: Vullien Aurore , Amiel Aldine R , Baduel Loeiza , Diken Dilara , Renaud Cécile , Krasovec Gabriel , Vervoort Michel , Röttinger Eric , Gazave Eve 
Published: December 2024

Abstract
Regeneration, the ability to restore body parts after injury, is widespread in metazoans; however, the underlying molecular and cellular mechanisms involved in this process remain largely unknown, and its evolutionary history is consequently unresolved. Recently, reactive oxygen species (ROS) have been shown in several metazoan models to be triggers of apoptosis and cell proliferation that drive regenerative success. However, it is not known whether the contribution of ROS to regeneration relies on conserved mechanisms. Here we performed a comparative genomic analysis of ROS metabolism actors across metazoans, and carried out a comparative study of the deployment and roles of ROS during regeneration in two different metazoan models: the annelid Platynereis dumerilii and the cnidarian Nematostella vectensis. We established that the vast majority of metazoans encode a core redox kit allowing for the production and detoxification of ROS, and overall regulation of ROS levels. However, the precise composition of the redox arsenal can vary significantly from species to species, suggesting that evolutionary constraints apply to ROS metabolism functions rather than precise actors. We found that while ROS are necessary for regeneration in both Platynereis and Nematostella, the two species deploy different enzymatic activities controlling ROS dynamics, and display distinct effects of ROS signaling on injury-induced apoptosis and cell proliferation. We conclude that, while ROS are a common feature of metazoan regeneration, their production and contribution to this phenomenon may depend on different molecular mechanisms highlighting the overall plasticity of the machinery.
Gene expression analysis of ovarian follicles and stromal cells in girls with Turner syndrome
Authors: Peek Ron , van der Coelen Sanne , Dolmans Marie-Madeleine 
Published: December 2024

Abstract
In patients with mosaic Turner syndrome, the ovarian somatic cells (granulosa and stromal cells) display a high level of aneuploidy with a 45,X karyotype, which may affect gene expression in the ovary and contribute to their reduced fertility. The aim of the current research is to study the effect of aneuploidy of somatic ovarian cells on gene expression in ovarian cortex stromal cells and small ovarian follicles from mosaic (45,X/46,XX) Turner syndrome patients. To this end, ovarian cortical tissue was obtained by laparoscopic surgery from eight mosaic Turner syndrome patients (aged 5–19 years) and eight controls (aged 6–18 years). The tissue was fractionated to obtain purified follicles and stromal cells. Part of the purified fractions was used to determine the X chromosomal content of ovarian cells of Turner syndrome patients by interphase FISH, while the remaining part was used to compare the gene expression profile of these cells to controls. The results demonstrated that high level 45,X haploidy in cortical stromal cells of Turner syndrome patients had no effect on gene expression, gross morphology of the ovary, or histological appearance of the cortex compared to controls. Gene expression analysis of purified small follicles of Turner syndrome patients with mainly 45,X granulosa cells revealed aberrant expression of 11 genes. Of these, six were upregulated (CD24, TLR1, EPHA2, PLXND1, ST6GALNAC5, and NOX4) while five genes (CRYAB, DLX1, PCYT2, TNFRSF8, and CA12) were downregulated compared to follicles of controls. Interestingly, the overexpressed genes in these small follicles were all associated with more advanced stages of follicular development. The consequences of this abnormal gene expression in follicles for Turner syndrome patients remain to be investigated, but they are likely to affect fertility.
Endometrial stromal cell signaling and microRNA exosome content in women with adenomyosis
Authors: Zipponi Margherita , Cacciottola Luciana , Camboni Alessandra , Stratopoulou Christina Anna , Taylor Hugh S , Dolmans Marie-Madeleine 
Published: December 2024

Abstract
Adenomyosis is a chronic, estrogen-driven disorder characterized by the presence of endometrial glands and stroma within the myometrium. Despite its significant impact on reproductive health and quality of life, the pathogenesis of the disease remains unclear. Both the glandular and stromal compartments of eutopic endometrium from women with adenomyosis show alterations compared to healthy subjects. However, the molecular mechanisms driving crosstalk between stromal cells and epithelial glands, along with paracrine signaling underlying lesion development and progression, are still poorly understood. Exosomes, small cell-derived carriers and microRNAs, namely non-coding RNA molecules, are crucial to intercellular communication within the endometrium and may elucidate interactions between the two compartments that contribute to adenomyotic lesion formation. To our knowledge, this is the first foundational study to comprehensively isolate and characterize stroma-derived exosomes from women with adenomyosis. Exosome isolation by means of differential ultracentrifugation was validated in 22 samples, including 11 healthy subjects and 11 women with adenomyosis, using nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry. Profiling of microRNA in secreted exosomes revealed 10 microRNAs with significantly altered expression in adenomyosis subjects during the menstrual phase compared to controls. Thorough investigations into menstruation-specific molecular mechanisms, as well as predicted target genes and enriched pathways of exosomal microRNAs, offer promising insights into the pathogenesis of adenomyosis, shedding light on the potential mechanisms underlying stromal cell signaling and adenomyotic lesion establishment. This work does, however, have certain drawbacks, including modest sample size and limited representation due to a lack of readily available endometrial biopsies in the menstrual phase. Having done the groundwork in this study, future research should seek to validate these findings in larger cohorts and apply functional assays. Indeed, our findings can serve as a resource to elucidate the role of menstruation-specific stroma-derived microRNA-mediated signaling and its potential impact on adenomyosis development.
Immunosenescence Inventory—a multi-omics database for immune aging research
Authors: Li Hao , Zhao Wei , Yang Fei , Qiao Qin , Ma Shuai , Yang Kuan , Song Shuhui , Wang Si , Qu Jing , Liu Guang-Hui , Bao Yiming , Zhang Weiqi 
Published: December 2024

Abstract
The immune system is intricately interconnected with all other bodily systems. As individuals age, the immune system undergoes changes known as immunosenescence, increasing susceptibility to disease, and contributing significantly to the morbidity and mortality observed in older populations. Immunosenescence drives systemic aging and therefore represents a key therapeutic target to extend healthy aging. In recent years, the extensive application of omics technologies has broadened our understanding of aging and immunity, necessitating a comprehensive database to encapsulate these advancements and deepen our insights into immune aging in the era of artificial intelligence. The Immunosenescence Inventory is a pioneering database designed to provide a multidimensional and integrative view of the aging immune system. By leveraging cutting-edge omics technologies and analytical tools, Immunosenescence Inventory offers a comprehensive resource for researchers to explore the intricate relationship between immunosenescence and age-related health outcomes. Furthermore, the database, which aids in the creation of diagnostic tools for immune aging conditions, is now publicly available at https://ngdc.cncb.ac.cn/iaa/home.
Programming ADAR-recruiting hairpin RNA sensor to detect endogenous molecules
Authors: Qin Pei-Pei , Chen Pin-Ru , Tan Liu , Chu Xiaohe , Ye Bang-Ce , Yin Bin-Cheng 
Published: December 2024

Abstract
RNA editing leveraging ADARs (adenosine deaminases acting on RNA) shows promising potential for in vivo biosensing beyond gene therapy. However, current ADAR sensors sense only a single target of RNA transcripts, thus limiting their use in different biosensing scenarios. Here, we report a hairpin RNA sensor that exploits new mechanisms to generate intramolecular duplex substrates for efficient ADAR recruitment and editing and apply it to detection of various intracellular molecules, including messenger RNA, small molecules and proteins. We utilize the base pairing interactions between neighbouring bases for enhanced stability, as well as the reverse effects to sense RNA transcripts and single-nucleotide variants with high sensitivity and specificity, irrespective of sequence requirement for complementarity to an UAG stop codon. In addition, we integrate RNA aptamers into the hairpin RNA sensor to realize the detection of the primary energy-supplying molecule, ATP, and a transcription factor, nuclear factor-kappa B (NF-κB), in live cells via a simple conformational change for programming the activation of hairpin RNA. This sensor not only broadens the detection of applicable molecules, but also offers potential for diverse cell manipulation.
Novel role of zinc-finger protein 518 in heterochromatin formation on α-satellite DNA
Authors: Ohta Shinya , Ohzeki Jun-Ichirou , Sato Nobuko , Tanizawa Hideki , Chung Claire Yik-Lok , Noma Ken-Ichi , Masumoto Hiroshi 
Published: December 2024

Abstract
Aneuploidy is caused by chromosomal missegregation and is frequently observed in cancers and hematological diseases. Therefore, it is important to understand the molecular mechanisms underlying chromosomal segregation. The centromere's intricate structure is crucial for proper chromosome segregation, with heterochromatin at the pericentromeric α-satellites playing a key role. However, the mechanism targeting heterochromatin to pericentromeres remains elusive. This study identifies a novel mechanism involving two homologous zinc-finger proteins ZNF518A and ZNF518B in human pericentric heterochromatin formation. Our investigation demonstrated that ZNF518s localize to the centromere via centromere protein B (CENP-B). Moreover, ZNF518s interact with heterochromatin protein 1 (HP1) and H3K9 methyltransferase G9A, recruiting the heterochromatin components to pericentromeres. We found that centromeric histone H3K9 trimethylation was diminished in the absence of ZNF518s when another H3K9 methyltransferase, SUV39H1, was depleted. In somatic cells, the ZNF518s-G9a axis is not the principal pathway for heterochromatin formation but plays a supplementary role. Furthermore, ZNF518s are involved in histone H3K9 trimethylation at ectopic sites, indicating their broad role in heterochromatin establishment. Consequently, we propose that ZNF518s participate in the mechanism underlying heterochromatin establishment at pericentromeres. Our findings shed light on the novel mechanism underlying pericentromeric heterochromatin formation, highlighting the central role of ZNF518 in this process.
Functional RNA mining using random high-throughput screening
Authors: Liu Li-Hua , Chen Jinde , Lai Shijing , Zhao Xuemei , Yang Min , Wu Yi-Rui , Zhang Zhiqian , Jiang Ao 
Published: December 2024

Abstract
Functional RNA participates in various life processes in cells. However, there is currently a lack of effective methods to screen for functional RNA. Here, we developed a technology named random high-throughput screening (rHTS). rHTS uses a random library of ∼250-nt synthesized RNA fragments, with high uniformity and abundance. These fragments are circularized into circular RNA by an auto-cyclizing ribozyme to improve their stability. Using rHTS, we successfully screened and identified three RNA fragments contributing significantly to the growth of Escherichia coli, one of which possesses coding potential. Moreover, we found that two noncoding RNAs (ncRNAs) effectively inhibited the growth of E. coli, in vivo rather than in vitro. Subsequently, we applied the rHTS to a coenzyme-dependent screening platform. In this context, two ncRNAs were identified that could effectively promote the conversion from NADPH to NADP+. Exogenous expression of these two ncRNAs was able to increase the conversion rate of glycerol dehydrogenase from glycerol to 1,3-dihydroxyacetone from 18.3% to 21.8% and 23.2%, respectively. These results suggest that rHTS is a powerful technology for functional RNA mining.