bluuebunny/crossref_metadata_2025 huggingface dataset:
Bending properties of human cartilaginous ribs and costal cartilage material vary with age, sex, and calcification
Authors: Goh Megan H , Anderson Dennis E
Published: December 2024

Costal cartilage plays an important functional role in the rib cage, but its mechanical properties have not been well characterized. The objective of this study is to characterize the properties of human costal cartilage and examine the effects of age, sex, rib level, and degree of calcification. We obtained cadaveric costal cartilage samples of ribs 3-6 with intact perichondrium from 24 donors (12 females and 12 males) evenly distributed by age (range 47-94 yr). Peripheral QCT scans were used to quantify geometric properties (area moments) and tissue calcification (as volume, length, and classified as central, peripheral, and mixed). Four-point bending tests were performed on each sample, and bending stiffness and modulus outcomes were evaluated by fitting data from mechanical testing with non-linear pseudo-elastic models (composed of linear and cubic components, separated into loading and unloading regimes). Effects of sex, age, rib level, and cartilage calcification on bending stiffness and modulus outcomes were assessed with mixed-effects regression models. Cartilage size (area moment) was larger in males than females and positively associated with age, while there was more calcification volume in cartilage of females than males. During loading, stiffness (linear and cubic) was larger in males, while modulus (linear and cubic) was larger in females. Linear stiffness and modulus were both negatively associated with age, positively associated with calcification, and varied between rib levels. Cubic (nonlinear) components of stiffness and modulus were positively associated with calcification and varied by rib, while modulus (but not stiffness) was negatively associated with age. During unloading, the linear stiffness and modulus values were much lower, though some similar associations were found. Overall, this study adds to our understanding of the behavior of costal cartilage as a nonlinear visco-elastic material, and the effects of sex, aging, and calcification on mechanical behavior.
Fault frequency band segmentation and domain adaptation with fault simulated signal for fault diagnosis of rolling element bearings
Authors: Park Jongmin , Yoo Jinoh , Kim Taehyung , Kim Minjung , Park Jonghyuk , Ha Jong Moon , Youn Byeng D
Published: December 2024

Rolling element bearings are vital components in rotating machinery, and ensuring their reliable operation through robust fault diagnosis is crucial in industrial settings. Deep-learning-based methods have shown promise due to their high accuracy, but they often face challenges in data acquisition and domain shifts between training and inference datasets. Existing approaches have attempted to address these issues through signal generation using simulation models, deep learning techniques, and domain adaptation under partial label scenarios. However, generated signals often lack plausibility or physical fidelity, and partial domain adaptation approaches frequently fail to incorporate fault-related knowledge. This paper proposes a novel method combining fault frequency band segmentation domain adaptation (FBSDA) with fault-added and uncertainty-aware signal simulation. To address the scarcity of fault-labeled signals, the proposed simulation method accounts for uncertainties in the signal acquisition environment by leveraging statistical cyclo-stationary modeling of fault bearings. By adding simulated fault signals to normal signals that contain system characteristic information, the generated signals more accurately reflect real-site environments and physical principles. Additionally, the FBSDA method, a domain adaptation approach focusing on segmenting fault-related information within the fault frequency band, is introduced. To enhance the focus on the fault frequency band, FBSDA employs a fault frequency segmentation module and a loss function inspired by image segmentation techniques. This method effectively reduces the domain gap between source and target domains and simultaneously captures fault information common to both simulated and real signals. The proposed method is validated through two case studies using different testbed datasets under various operating conditions. The results demonstrate the superior performance of our approach in handling domain shifts and different levels of partial labels, outperforming existing signal generation and domain adaptation methods. The proposed method also has a practical value in that the target bearing system can be diagnosed using physical knowledge even in the absence of fault signals that are difficult to obtain.
First detection of Bemisia tabaci (Hemiptera: Aleyrodidae) MED in Oklahoma and development of a high-resolution melting assay for MEAM1 and MED discrimination
Authors: Krause-Sakate Renate , Gomes Ruschel Rafaela , Ochoa-Corona Francisco , Andreason Sharon A , de Marchi Bruno Rossito , Ribeiro-Junior Marcos Roberto , Nascimento Daniele Maria , Trujillo Reese , Smith Hugh A , Hutton Samuel F , Wallace Sara
Published: December 2024

The sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is a polyphagous pest recognized as composed of several cryptic or sibling species. The Middle East-Asia Minor 1 (MEAM1) and the Mediterranean (MED) putative species are invasive and destructive worldwide. The MEAM1 is established throughout the United States, while MED is documented in 27 states. This study determines the status of MED in Oklahoma and develops and validates a high-resolution melting (HRM) assay for discrimination of MEAM1 and MED. In August–October 2022, whiteflies were collected from different host plants in Stillwater, Oklahoma, and identified as species based on analysis of a diagnostic fragment of the mitochondrial cytochrome oxidase I (mtCOI) gene. MED was found in mixed infestations with MEAM1 on both sweetpotato in a greenhouse and cucumber in the field. Other cryptic species were not detected. Sequencing followed by phylogenetic analysis indicated that the MED specimens belonged to the Q2 mitotype. Additionally, the secondary endosymbionts in captured and progeny whiteflies were identified. For rapid discrimination of MEAM1 and MED species, an HRM assay using a single set of primer pairs targeting the mtCOI gene was developed. Species discrimination was tested in 2 laboratories using MEAM1 and MED Q2 mitotype genomic DNA, and a synthetic plasmid containing the MED Q1 mitotype mtCOI fragment. The HRM assay was validated to discriminate MEAM1 from MED Q1 and Q2 mitotypes. This is the first report of B. tabaci MED in Oklahoma and reinforces the need for continued monitoring of this insect species complex.
Hidden invaders: intraspecific cryptic invasion and hybridization of Dolichoderus thoracicus (Hymenoptera: Formicidae) in Taiwan
Authors: Hsu Feng-Chuan , Chen Joanne Tzu-Chia , Yamada Aiki , Hsiao Yun , Ho Chuan-Kai , Lin Chung-Chi , Oguri Emiko , Tseng Shu-Ping
Published: December 2024

Biological invasions pose substantial threats to global biodiversity, agriculture, and ecological stability. Among these, intraspecific cryptic invasions, characterized by the spread of nonnative genotypes within a species, present unique challenges for detection and management. Despite the well-documented influence of invasive ants on ecosystems, instances of intraspecific cryptic ant invasions have rarely been documented. This study focused on the black cocoa ant, Dolichoderus thoracicus (Smith 1860), which has been increasingly reported as a pest in Taiwan over the past decade. In this study, we utilized a genome-wide approach employing multiplexed inter-simple sequence repeats genotyping by sequencing to identify single nucleotide polymorphisms across the D. thoracicus populations, elucidating the variations in the genetic population structure of the species in Taiwan. Our findings confirmed the occurrence of intraspecific cryptic invasions, demonstrating the coexistence of native and nonnative lineages, along with potential hybridization events between them. This study underscores the critical role of comprehensive genetic analysis in uncovering the complex dynamics of species invasions.
Telling Meaningful Stories About Climate Change and Public Law
Authors: Fisher Elizabeth
Published: December 2024

Current scholarly discourse is dominated by stories about the role of strategic litigation as a mechanism for forcing public action in relation to climate change. While such stories are satisfying, they are not necessarily meaningful because they narrow the intellectual field of vision. By using an essay by Ursula Le Guin on narrative forms, I show that other more meaningful narratives are possible to tell. Narratives that encompass a bigger picture and, in so doing, draw attention to how public law is a resource for the institutional and reasoning capacity required for responding to the polycentric and multivalent nature of climate change. Such capacity does not provide a ‘solution’ to climate change but does underscore the need to foster legal and scholarly expertise and imagination in relation to climate change and public law.
Bolivia’s resistance to modification and commodification of seeds: challenges in aligning domestic situation with its international position
Authors: Ghimire Saurav , Van der Borght Kim , Frison Christine
Published: December 2024

Based on the concept of vivir bien, Bolivia has developed laws resisting modification and commodification of genetic resources. It has played an important role in international forums in promotion of these ideas and has been contributing to international law-making for farmers’ rights. From the perspective of farmers’ rights to seeds, this article examines Bolivia’s Plant Variety Protection (PVP) legislation and the cultivation of genetically modified soybean, the crop most frequently protected under PVP. This article argues that, while Bolivia has laws discouraging the modification and commodification of seeds and has been internationally resisting the same in favour of farmers’ rights, domestically the soybean farmers cannot exercise their minimally recognized rights of saving seeds under the PVP law. This article shows that mere exception to save seeds is not adequate to retain farmers’ ownership over the seeds, particularly in industrial farming. Therefore, the seed suppliers can exercise more rights than granted by law, ultimately securing the repeated purchase of seeds even from the smallholders. Besides, this article shows how the agro-industrial sector has influenced the government and has successfully accommodated their interest in the broader political objectives of food sovereignty and farmers’ rights. This article ultimately proposes that enabling smallholders soybean farmers to exercise their legally recognized right to save and repeatedly use their own seeds could be one of the means to protect them from the agricultural exclusion currently happening in the soybean sector in Bolivia.
Patent quality matters
Authors: Baldus Oliver
Published: December 2024

Patent quality can be determined reliably based on three distinct quality objectives, namely legal framework (legal quality), prior art (substantial quality) and market potential (economic quality). The legal quality of a patent is given by compliance with all legal requirements of the underlying legal framework. The substantial quality of a patent is given by the likelihood that a patent will not be invalidated based on prior art. The economic quality of a patent is given by the market potential of the subject matter protected by the patent.
Effects of elicitors on plant host selection by adult Leptinotarsa decemlineata (Coleoptera: Chrysomelidae)
Authors: Butcher Alexander , Rondon Silvia I , Lee Jana , Paul Ryan
Published: December 2024

The Colorado Potato Beetle, Leptinotarsa decemlineata Say, is the principal defoliator of potato crops globally. It is well known for its propensity to rapidly develop resistance. Thus, new control options which are resilient to the pest’s resistance capabilities are a critical need. The use of chemical ecology in integrated pest management (IPM) programs has been proposed as a means to delay resistance. Elicitors are chemical growth regulators that activate plant defenses. These plant defenses provide numerous opportunities to integrate chemical ecology into IPM programs, including changes to a plants volatile profile. In this laboratory study, we provide evidence that elicitors which mimic jasmonic acid (JA) and salicylic acid (SA) can be used to attract or repel L. decemlineata respectively. Adult beetles are highly attracted to potato plants sprayed with the JA mimicking elicitor Blush 2X, while plants sprayed with SA mimicking elicitor, Actigard 50WG, appear to be repellent. Additionally, residency time on plants sprayed with Actigard 50WG was significantly shorter than with control plants. The potential use of elicitors within IPM program is discussed.
Association of plasma branched-chain amino acid levels with colorectal cancer risk in a nested case–control study
Authors: Hisada Izumi , Yamaji Taiki , Sawada Norie , Inoue Manami , Tsugane Shoichiro , Iwasaki Motoki ,   Japan Public Health Center-Based Prospective Study Group
Published: December 2024

Background

Intake of branched-chain amino acids (BCAA) has been suggested to have a prophylactic effect against carcinogenesis in colorectal cancer (CRC). However, the possible effect of plasma BCAA concentration has not been fully evaluated.

Methods

We conducted a prospective case–control study within a cohort of four public health center areas for which blood sample and questionnaire data from a 5-year follow-up survey were available. We identified 360 newly diagnosed CRC cases during the follow-up period and selected two matched controls for each case. We estimated odds ratio (OR) and 95% confidence intervals (CI) for CRC using conditional logistic regression models adjusted for potential confounding factors.

Results

Increased plasma concentrations of BCAAs were not inversely associated with CRC risk after adjustment for potential confounders. Compared with the lowest quartile, ORs in the highest quartile of leucine, isoleucine, valine, and total BCAA were 0.74 (95% CI, 0.49–1.12), 0.85 (0.56–1.29), 0.75 (0.50–1.13), and 0.70 (0.47–1.05), respectively. After excluding cases diagnosed within the first 6 years of follow-up, total BCAA and leucine were significantly related to a decreased risk of CRC, with ORs in the highest quartile of total BCAA and leucine of 0.58 (0.35–0.96) and 0.56 (0.33–0.93), respectively.

Conclusions

We found no statistically significant inverse association between plasma BCAA concentrations and CRC risk in overall analyses, whereas on 6-year exclusion, total BCAA and leucine were associated with decreased CRC risk. Plasma BCAA concentrations may play a prophylactic role in colorectal carcinogenesis, and further investigation is warranted.
Patronage Networks, Personal Ties, and Political Selection: Evidence from a New Group of Subnational Officials in China
Authors: Si Ruichao , Xu Gang
Published: December 2024

The current literature has paid much attention to the political selection of China’s subnational party secretaries and government executives (e.g., provincial governors). However, the party’s rule of collective leadership dictates that it is the Chinese Communist Party Provincial Standing Committee (PPSC), a group of officials with substantial power over local affairs, that collectively rules the province. How the members of PPSC are selected and promoted remains surprisingly understudied. This article fills this gap by examining how various types of personal connections with senior leaders can account for their career advancements. Empirical results show that they are more likely to be promoted if the provincial party secretary who once promoted them to the PPSC members later becomes a national leader. Further evidence indicates that this promotion-based patronage network fosters loyalty of junior officials to senior ones. Finally, we show that such patronage may also jeopardize the clients’ political careers during purges. (JEL D72, H77, P27)
Acceptability of an organ inventory for cancer screening across gender identity and intersex status
Authors: Moseson Heidi , Ragosta Sachiko , Gómez Anu Manchikanti , Corman Jae , Zussman Jay , Lesser-Lee Bori , Reese Sydney , Carter-Bolick India Rose , Obedin-Maliver Juno
Published: December 2024

Objectives

To evaluate the acceptability and performance of an organ inventory as an alternative to asking about gender and/or sex assigned at birth in cancer screening.

Methods

We fielded an online, self-administered survey to a convenience sample of English- or Spanish-speaking transgender and gender-diverse (TGD), intersex, and cisgender people (≥15 years) in the United States. The survey contained an organ inventory developed with community input and questions regarding acceptability. The primary outcome was organ inventory acceptability by the 4-item Acceptability of Intervention Measure (AIM). Additional outcomes included inter-method screening agreement between the organ inventory, gender, and sex assigned at birth.

Results

In 2022, 333 eligible individuals completed the survey: 44.4% cisgender, 34.2% TGD, and 14.1% intersex. Overall, participants rated the organ inventory as acceptable (median AIM score = 18/20, IQR: 16-20). Most of them found it easy to understand (73%) and comfortable to complete (65%). Cancer screening eligibility varied based on the method used; relying solely on gender or sex data would have missed some eligible participants that the organ inventory identified.

Conclusions

Using an organ inventory as an alternative to gender- or sex-based screening questions was acceptable and has implications for addressing cancer screening disparities.
Improving real-world evaluation of patient- and physician-reported tolerability: niraparib for recurrent ovarian cancer (NiQoLe)
Authors: Joly Florence , Bazan Fernando , Garbay Decoopman Delphine , Ouldbey Yaelle , Follana Philippe , Champeaux-Orange Élise , Legouffe Eric , Brachet Pierre-Emmanuel , Spaeth Dominique , Combe Pierre , Hardy-Bessard Anne-Claire , Selle Frédéric , Grenier Julien , Lebreton Coriolan , Derbel Olfa , Bonnet Elise , Fournel Pierre , Fernandez Diez Yolanda , Delecroix Valérie , Emambux Sheik , Alexandre Jérôme , Grellety Thomas , Mille Dominique , Orfeuvre Hubert , Favier Catherine , Le Roux Delphine , Mouret-Reynier Marie-Ange , Quesada Stanislas , Kurtz Jean-Emmanuel
Published: December 2024

Background

Maintenance niraparib at an individualized starting dose (ISD) is established in platinum-sensitive recurrent ovarian cancer (PSROC). However, patients’ perspectives on the burden of prolonged maintenance therapy have not been reported in prospective trials or routine practice.

Methods

In the real-life multicenter NiQoLe study, patients with PSROC received ISD maintenance niraparib. The primary objective was to describe physician-reported adverse events (AEs) leading to treatment modification during the first 3 months. Secondary endpoints included patient-reported outcomes (symptomatic AEs using PRO-CTCAE, self-reported fatigue and impact on daily activities/function using FACT-F) collected remotely weekly using a specifically designed electronic device.

Results

Most (80%) of 139 treated patients (median age 70 years) began niraparib at 200 mg/day. Median treatment duration was 5.7 (range 0.2–21.4) months. During the first 3 months, 86 patients (62%) required treatment modification (median 27 days to modification). Physician-reported grade ≥3 niraparib-related AEs occurred in 34 patients (24%); 68 patients (49%) had treatment modification for AEs, predominantly thrombocytopenia. The most frequent patient-reported AEs (PRO-CTCAE) were fatigue, insomnia, constipation, and dry mouth. Self-reported AEs were severe in 66% of patients. At baseline, 33% of patients reported severe fatigue (FACT-F), which generally persisted during niraparib. Physicians systematically underestimated major patient-reported symptoms.

Conclusions

In routine practice, dose modification was often required during the first 3 months despite individualized dosing. Physicians underestimated the burden of fatigue and symptomatic AEs. Digital self-reporting of AEs is feasible, provides patient-centered information complementing physician-reported AEs, and allows fuller appreciation of toxicity in real-world studies.

Clinical trial information

NCT03752216
Assessment of adherence to the Infectious Diseases Society of America guidelines for treating suspected meningitis in adults: a retrospective observational study
Authors: Mohialdin Dina , Abu-Farha Rana , ALkhawaldeh Rama , Al-Ashwal Fahmi Y , Abu Hammour Khawla
Published: December 2024

Objectives

This study aimed to assess physicians’ adherence to the Infectious Diseases Society of America (IDSA) guidelines in managing and treating adult patients (≥ 18 years old) admitted with suspected cases of meningitis and to investigate any associations between guideline adherence and hospital length of stay (LOS) as well as all-cause mortality among these patients.

Methods

This retrospective observational study was conducted at a tertiary care hospital in Jordan, focussing on adult patients admitted with suspected meningitis between 1 January 2019 and 30 September 2022. The study aimed to assess the appropriateness of antibiotic prescriptions before culture results according to IDSA guidelines and calculate the overall adherence rate. Additionally, the study observed hospital LOS and all-cause mortality among the enrolled patients.

Key findings

Of the enrolled adult patients (n = 118), 14.4% (n = 17) were diagnosed with bacterial meningitis. Notably, only five patients (4.2%) were treated appropriately, adhering entirely to the IDSA guidelines, whereas the remaining 95.8% (n = 113) showed various forms of non-adherence to these recommendations. The highest adherence to IDSA recommendations was observed in performing cerebrospinal fluid culture (100%), whereas the lowest adherence was noted in selecting appropriate doses and durations for the empiric antibiotics (n = 18, 26.5% and n = 21, 30.9%, respectively). No significant associations were found between adherence to IDSA treatment guidelines and hospital LOS (P = .100) or all-cause mortality (P = .332) among these patients.

Conclusion

This study revealed low overall adherence to IDSA guidelines among adult patients. Key areas for improvement in management include promptly selecting appropriate empiric antibiotics with correct dosing and duration to mitigate adverse effects and prevent bacterial resistance.
Decoding the power of saponins in ferroptosis regulation and disease intervention: a review
Authors: Ouyang Min , Wu Jianhua , Hu Xizhuo , Liu Changfu , Zhou Dan
Published: December 2024

Objectives

This review endeavors to elucidate the complex interplay underlying diseases associated with ferroptosis and to delineate the multifaceted mechanisms by which triterpenoid and steroidal saponins modulate this form of cell death.

Methods

A meticulous examination of the literature was undertaken, drawing from an array of databases including Web of Science, PubMed, and Wiley Library, with a focus on the keywords “ferroptosis,” “saponin,” “cancer,” “inflammation,” “natural products,” and “signaling pathways.”

Key findings

Ferroptosis represents a distinctive mode of cell death that holds considerable promise for the development of innovative therapeutic strategies targeting a wide range of diseases, especially cancer and inflammatory disorders. This review reveals the nuanced interactions between saponins and critical signaling pathways, including system Xc−-GSH-GPX4, Nrf2, p53, and mTOR. These interactions highlight the dual capacity of saponins to modulate ferroptosis, thereby offering fresh perspectives for therapeutic intervention.

Conclusions

The insights garnered from this review significantly advance our comprehension of the dynamic relationship between saponins and ferroptosis. By shedding light on these mechanisms, this work sets the stage for leveraging these insights in the creation of pioneering approaches to disease treatment, marking a significant stride in the evolution of therapeutic modalities.
Robustness, model checking, and hierarchical models
Authors: Cabral Rafael , Bolin David , Rue Håvard
Published: December 2024

Model checking is essential to evaluate the adequacy of statistical models and the validity of inferences drawn from them. Particularly, hierarchical models such as latent Gaussian models (LGMs) pose unique challenges as it is difficult to check assumptions on the latent parameters. Diagnostic statistics are often used to quantify the degree to which a model fit deviates from the observed data. We construct diagnostic statistics by (a) defining an alternative model with relaxed assumptions and (b) deriving the diagnostic statistic most sensitive to discrepancies induced by this alternative model. We also promote a workflow for model criticism that combines model checking with subsequent robustness analysis. As a result, we obtain a general recipe to check assumptions in hierarchical models and the impact of these assumptions on the results. We demonstrate the ideas by assessing the latent Gaussianity assumption, a crucial but often overlooked assumption in LGMs. We illustrate the methods via examples utilizing Stan and provide functions for easy usage of the methods for general models fitted through R-INLA.
The first case of combined pancreatic neuroendocrine tumour and neuroendocrine carcinoma
Authors: Lun Tegan , Rosty Christophe , Palamuthusingam Pranavan
Published: December 2024

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

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 (<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.
Protracted Katayama syndrome in an immunocompromised traveller: the challenge of assessing cure
Authors: Van Den Broucke Steven , Schrijvers Rik , Van Esbroeck Marjan , Coppens Jasmine , Van Lieshout Lisette , Bottieau Emmanuel
Published: December 2024

We describe a case of prolonged Katayama syndrome in an immunocompromised traveller. We highlight the difficulty of evaluating a cure due to persistent polymerase chain reaction (PCR) positivity and fluctuating markers. We discuss limitations of current diagnostic assays and advocate for improved access to reliable markers like the circulating anodic antigen test.
Self-Directed Skills Laboratories Increase Emergency Medicine Physician Confidence in High-Acuity, Low-Opportunity Procedures
Authors: Stuart Sean M , Aubuchon Thomas
Published: December 2024

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

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 < .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

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

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

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

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

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

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

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.