bluuebunny/crossref_metadata_2025 huggingface dataset:
Paleomagnetic inclinations and relative paleointensity variations during the upper Aptian to middle Albian in Sergipe-Alagoas Basin, South Atlantic Ocean (NE Brazil)
Authors: Gewehr de Mello Raquel , Savian Jairo F , Fauth Gerson , Florindo Fabio , Di Chiara Anita , Satolli Sara , Roisenberg Henrique B , Leandro Carolina G , Lopes Camila Trindade , Pontel Caroline A , Frigo Everton , Santos Alessandra , Baecker-Fauth Simone , Bruno Mauro D R , Guerra Rodrigo M , Krahl Guilherme , Kochhann Karlos G D , Lopes Fernando M , Trindade Ricardo I F , Spagnuolo Lilla
Published: December 2024

During the Jurassic and Early Cretaceous, Earth's magnetic field experienced a high frequency of polarity reversals. This hyperactivity period is followed by a ∼38 Myr prolonged period of stable normal polarity from the Aptian until the Santonian, known as the Cretaceous Normal Superchron (CNS; chron C34n, from 121.4 to 83.65 Ma). However, the CNS might have been characterized by more variability than previously thought, but the current database is uneven in its spatial and temporal distribution. In this study, we integrate paleomagnetic and biostratigraphic data from the SER-03 sedimentary core, drilled onshore in the Sergipe-Alagoas Basin, NE Brazilian margin, South Atlantic Ocean. The 183-m cored interval spans 5.2 Myr (114.7–109.5 Ma), including the Aptian–Albian transition. It records the evolution from restricted marine settings to the complete opening of the South Atlantic Ocean. Magnetic remanence and rock magnetic parameters, such as magnetic susceptibility, anhysteretic remanent magnetization and isothermal remanent magnetization, were measured. Rock magnetic analyses indicated that primary magnetizations were preserved throughout the interval, with detrital magnetite identified as the primary magnetic carrier, predominantly in the pseudo-single domain and low-coercivity states. Normalizations by χ, ARM15mT and IRM15mT were used to determine relative paleointensity curves and were compared to the curve resulting from the pseudo-Thellier method. The SER-03 relative paleointensity record shows marked changes in both intensity and inclination. Inclination instability results are comparable with those found in volcanic rocks from surrounding the region. The high-resolution SER-03 magnetic record revealed that the field variability was higher than expected during the CNS, but remaining substantially lower than during other periods, such as the late Jurassic. The new SER-03 can serve as a dating and correlation tool for coeval records.
An endoplasmic reticulum stress related signature for clinically predicting prognosis of breast cancer patients
Authors: Qiao Enqi , Ye Jiayi , Huang Kaiming
Published: December 2024

Background

Endoplasmic Reticulum Stress (ER stress) was an important event in the development of breast cancer. We aimed to predict prognosis based on ER stress related key genes.

Methods

Data of the RNA-seq and clinical information of breast cancer cases were downloaded from the TCGA database. A total of 4 genes related with ER stress was identified by the univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the ER stress model was evaluated by utilizing Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. Moreover, we verified 4 genes expression and its relationship with clinical breast cancer cases in real-world.

Results

4 genes including RNF186, BCAP31, SERPINA1, TAPBP were identified as a prognostic risk score model. Based on that, we found patients of breast cancer had a better survival with low-risk score. And also, ER stress model showed a good diagnostic efficacy with AUC curve. The risk score was significantly associated with patients’ age, T stage and clinical stage. A nomogram was constructed to estimate individual survival. Further GO and KEGG analysis showed our model was related with immune infiltration. Patients of breast cancer with high-risk scores were usually accompanied with poor immune infiltration. It was predicted that high risk group was more sensitive to Vinorelbine, Docetaxel and Cisplatin. At last, we verified the expression of four signature genes using qRT-PCR and immunohistochemistry.

Conclusion

Our ER stress model performed a valuable prediction on breast cancer patients.
Development of a riboflavin-responsive model of riboflavin transporter deficiency in zebrafish
Authors: Choueiri Catherine M , Lau Jarred , O’Connor Emily , DiBattista Alicia , Wong Brittany Y , Spendiff Sally , Horvath Rita , Pena Izabella , MacKenzie Alexander , Lochmüller Hanns
Published: December 2024

Riboflavin transporter deficiency (RTD) is a rare and progressive neurodegenerative disease resulting from the disruption of RFVT2- and RFVT3- mediated riboflavin transport caused by biallelic mutations in SLC52A2 and SLC52A3, respectively. The resulting impaired mitochondrial metabolism leads to sensorimotor neurodegeneration and symptoms including muscle weakness, respiratory difficulty, and sensorineural deafness. Although over 70% of patients with RTD improve following high-dose riboflavin supplementation, remaining patients either stabilise or continue to deteriorate. This may be due to the rapid excretion of central nervous system (CNS) riboflavin by organic anion transporter 3 (OAT-3), highlighting the need for alternative or supplemental RTD treatments. Probenecid is a promising therapeutic candidate for RTD due to its known inhibitory effect on OAT-3. Therefore, this study aimed to generate morpholino-mediated knockdowns of human SLC52A3 ortholog slc52a3 in zebrafish larvae for use in therapeutic screening of riboflavin and probenecid. Knockdown of slc52a3 resulted in an RTD-like phenotype indicative of altered neurodevelopment, hearing loss, and reduced mobility. This RTD-like phenotype overlaps with the phenotype of CRISPR/Cas9-mediated knockout of slc52a3 in zebrafish, is maintained following slc52a3 morpholino + p53 morpholino co-injection, and is rescued following slc52a3 morpholino + human SLC52A3 mRNA co-injection, indicating specificity of the knockdown. Riboflavin treatment alone ameliorates locomotor activity and hearing ability in slc52a3 morphants. Riboflavin and probenecid co-treatment provides an additional small benefit to hearing but not to locomotion. Our findings demonstrate that this model recapitulates both the RTD phenotype and the riboflavin-responsiveness of RTD patients, and possible therapeutic benefit conferred by probenecid warrants further investigation.
LoBLH6 interacts with LoMYB65 to regulate anther development through feedback regulation of gibberellin synthesis in lily
Authors: Yu Junpeng , Wu Ze , Liu Xinyue , Fang Qianqian , Pan Xue , Xu Sujuan , He Man , Lin Jinxing , Teng Nianjun
Published: December 2024

The homeostasis of gibberellin (GA) is crucial for the normal development of anthers, but its underlying regulatory mechanisms are not clear. The GA induced v-Myb myeloblastosis viral oncogene homolog (MYB) transcription factor LoMYB65 is involved in anther development. In this study, we screened and identified an interacting protein of LoMYB65, Lilium Oriental Hybrids BEL1-Like Homeodomain6 (LoBLH6). LoBLH6 was localized in both the nucleus and cytoplasm, and it interacted with LoMYB65 through its BELL domain, exhibiting transcriptional repression activity. LoBLH6 was continuously expressed during anther development, with particularly high expression in the mid and late stages. In situ hybridization revealed high expression of LoBLH6 in the tapetum and microspores, with the same tissue specificity as LoMYB65. Silencing of LoBLH6 in lilies resulted in abnormal anther development, reduced pollen, and increased GA content. The application of GA induced phenotypes in the anthers and pollen of lily that were similar to the silencing of LoBLH6. Further research showed that LoBLH6 directly binds to the promoter of Lilium Oriental Hybrids GA 20-oxidase1 (LoGA20ox1) to suppress its expression, and co-expression with LoMYB65 enhances this repression. Additionally, GA treatment enhanced the interaction between LoBLH6 and LoMYB65 and their complex's inhibitory effect on downstream target genes. During the transition from microspores to mature pollen grains in lily anthers, GA levels maintain a steady state, which is disrupted by silencing LoBLH6, leading to abnormal pollen development. Overall, our results reveal that the interaction between LoBLH6 and LoMYB65 regulates anther development through feedback regulation of GA synthesis.
Dexamethasone Upregulates the Expression of the Human SLC26A3 (DRA, Down-Regulated in Adenoma) Transporter (an IBD Susceptibility Gene) in Intestinal Epithelial Cells and Attenuates Gut Inflammation
Authors: Kumar Anoop , Husain Nazim , Anbazhagan Arivarasu N , Jayawardena Dulari , Priyamvada Shubha , Singhal Megha , Jain Charu , Kaur Prabhdeep , Guzman Grace , Saksena Seema , Dudeja Pradeep K
Published: December 2024

Background

Down-Regulated in Adenoma (DRA) plays a critical role in intestinal chloride absorption and a decrease in its expression is a key event in diarrheal disorders. Recently, DRA has emerged as an Inflammatory Bowel Disease (IBD) susceptibility gene. Therefore, the strategies to upregulate DRA expression are potentially novel approaches to not only treat IBD-associated diarrhea but also gut inflammation. In this study, the effect of dexamethasone (DEX), an anti-inflammatory corticosteroid on DRA expression was investigated.

Methods

GR (glucocorticoid receptor) overexpressed Caco-2 cells and C57BL/6/J mice and anti-αIL-10R mAb model of IBD were used. Protein expression was assessed by immunoblotting and immunofluorescence. Transcript levels were assessed by quantative-real-time polymerase chain reaction (qRT-PCR) and promoter activity was measured by luciferase assays.

Results

Our results showed that DEX significantly increased DRA mRNA and protein expression in GR overexpressing Caco-2 cells. DEX-induced upregulation of DRA was GR dependent and appeared at least in part to occur via a transcriptional mechanism, as promoter activity of the DRA construct (−1183/+114 bp) was significantly increased in response to DEX. The increase in DRA mRNA was abrogated in the presence of MKP-1 inhibitor, triptolide. Administration of DEX (2 mg/kg body weight) to mice for 24 and 48 hours significantly increased the DRA expression in mouse colon. DEX treatment to mice for 7 days in the αIL-10R mAb model of colitis was able to significantly attenuate the gut inflammation and associated decrease in DRA expression.

Conclusions

We demonstrate that DEX stimulates DRA expression via transcriptional mechanisms and suggest that upregulation of DRA may contribute to both anti-inflammatory and pro-absorptive effects of DEX.
Community pharmacists’ readiness for minor ailment services in Saudi Arabia: a cross-sectional study of perceptions, barriers, and facilitators
Authors: Alzahrani Fahad , Khairi Nosaiba B , Alattas Baraah O , Alrehaili Toqa H , Aljehani Ghadeer S , Alahmadi Renad B , Refi Dalia Mohammed , Aljohani Lama S , Fadil Haifa Abdulrahman , Alnezary Faris S , Al Thaqfan Sultan S
Published: December 2024

Objectives

Minor ailments are a significant burden on primary care services globally. In Saudi Arabia’s evolving healthcare landscape, pharmacists play a crucial informal role, but no coordinated national approach exists. Understanding pharmacists’ preparedness is thus vital to optimize successful integration. This study evaluated Saudi community pharmacists’ perceptions, barriers, and facilitators related to minor ailment services (MAS) for capacity-building strategies.

Methods

A cross-sectional survey was conducted from April to July 2023. Data were collected from participants using a self-administered, anonymous questionnaire with 48 questions. The data were analyzed using descriptive and inferential statistics in SPSS v.27.

Key findings

Of the 720 pharmacists invited to participate, 442 completed the questionnaire, yielding an overall response rate of 61.4% (442/720). Most pharmacists recognized the value of accessible self-care support using their skills (92.6%), but 26.9% feared misdiagnosis risks. Most (93.9%) emphasized prudent triage and history-taking, and yet 22.2% were ambivalent on referrals. Key barriers that were identified included the lack of patient information (71.5%), lack of reimbursement for MAS (61.8%), lack of a private/counseling area (59.5%), and lack of knowledge for minor ailment management (48.2%). Pharmacists who work in rural areas, work part-time, and have not attended any training or education programs also tend to display a more uncertain attitude toward delivering services for minor ailments.

Conclusions

Pharmacists in Saudi Arabia can play a significant role in managing minor ailments, but the identified barriers must be addressed to integrate their services thoroughly. That can be done through comprehensive training, allocating resources, and establishing structured communication and referral pathways. This integration can improve healthcare accessibility, reduce costs, and better utilize pharmacists’ expertise for delivering patient care.
Rational Weighted Projective Hypersurfaces
Authors: Esser Louis
Published: December 2024

A very general hypersurface of dimension $n$ and degree $d$ in complex projective space is rational if $d \leq 2$, but is expected to be irrational for all $n, d \geq 3$. Hypersurfaces in weighted projective space with degree small relative to the weights are likewise rational. In this paper, we introduce rationality constructions for weighted hypersurfaces of higher degree that provide many new rational examples over any field. We answer in the affirmative a question of Okada about the existence of very general terminal Fano rational weighted hypersurfaces in all dimensions $n \geq 6$.
Evaluation of joint external evaluation to COVID-19 and other infectious diseases mortality outcomes in 96 countries
Authors: Lee Yuri , Kim Siwoo , Lee Sieun , Kim Min Kyung , Gostin Lawrence O , Oh Juhwan
Published: December 2024

Background

This study evaluated the effectiveness of Joint External Evaluation (JEE) scores with regard to coronavirus disease 2019 (COVID-19) and other infectious diseases performance in 96 countries. To propose a revised JEE tool, potential JEE indicators were also examined.

Methods

JEE data from 2016–2019 were linked with outcomes such as COVID-19 fatality rates and infections, as well as mortality rates for other infectious diseases. We also examined potential indicators such as the Sustainable Development Goals (SDGs) and Universal Health Coverage index to propose enhancements to the JEE tool. Multiple regression analysis was used to assess these associations.

Results

The average JEE score was 2.70 (SD=0.92) in 96 countries. Detection capabilities received the highest average score (3.23), while the other areas (2.30) section received the lowest scores. However, the analysis revealed that the JEE tool had limited predictive accuracy for COVID-19 outcomes. By contrast, the JEE scores showed a negative association with the performance of other infectious diseases. Notably, SDGs 2 (zero hunger), 4 (quality education) and 8 (decent work and economic growth) were strongly associated with better COVID-19 outcomes.

Conclusion

The JEE scores showed limited predictive value for COVID-19 mortality outcomes in 96 countries. The tool offers insights into health security, but needs revision to better handle future pandemics.
Virophage infection mode determines ecological and evolutionary changes in a host-virus-virophage system
Authors: del Arco Ana , Becks Lutz
Published: December 2024

Giant viruses can control their eukaryotic host populations, shaping the ecology and evolution of aquatic microbial communities. Understanding the impact of the viruses’ own parasites, the virophages, on the control of microbial communities remains a challenge. Most virophages have two modes of infection. They can exist as free particles coinfecting host cells together with the virus, where they replicate while inhibiting viral replication. Virophages can also integrate into the host genome, replicate through host cell division and remain dormant until the host is infected with a virus, leading to virophage reactivation and replication without inhibiting viral replication. Both infection modes (reactivation vs. coinfection) occur within host-virus-virophage communities, and their relative contributions are expected to be dynamic and context dependent. The consequences of this dynamic regime for ecological and evolutionary dynamics remain unexplored. Here, we test whether and how the relative contribution of virophage infection modes influences the ecological dynamics of an experimental host-virus-virophage system and the evolutionary responses of the virophage. We indirectly manipulated the level of virophage (Mavirus) integration into the host (Cafeteria burkhardae) in the presence of the giant Cafeteria roenbergensis virus. Communities with higher virophage integration were characterized by lower population densities and reduced fluctuations in host and virus populations, whereas virophage fluctuations were increased. The virophage evolved toward lower inhibition and higher replication, but the evolution of these traits was weaker with higher virophage integration. Our study shows that differences in the virophage infection modes contributes to the complex interplay between virophages, viruses and hosts.
Ceftolozane/tazobactam disrupts Pseudomonas aeruginosa biofilms under static and dynamic conditions
Authors: Kostoulias Xenia , Fu Ying , Morris Faye C , Yu Crystal , Qu Yue , Chang Christina C , Blakeway Luke , Landersdorfer Cornelia B , Abbott Iain J , Wang Lynn , Wisniewski Jessica , Yu Yunsong , Li Jian , Peleg Anton Y
Published: December 2024

Background

Pseudomonas aeruginosa biofilms limit the efficacy of currently available antibacterial therapies and pose significant clinical challenges. Pseudomonal biofilms are complicated further when other markers of persistence such as mucoid and hypermutable phenotypes are present. There is currently a paucity of data regarding the activity of the newer β-lactam/β-lactamase inhibitor combination ceftolozane/tazobactam against P. aeruginosa biofilms.

Methods

We evaluated the efficacy of ceftolozane/tazobactam against clinical P. aeruginosa isolates, the laboratory isolate PAO1 and its isogenic mutS-deficient hypermutator derivative (PAOMS) grown under static and dynamic biofilm conditions. The clinical isolate collection included strains with mucoid and hypermutable phenotypes.

Results

Ceftolozane/tazobactam exposure led to a bactericidal (≥3 log cfu/cm2) biofilm reduction in 15/18 (83%) clinical isolates grown under static conditions, irrespective of carbapenem susceptibility or mucoid phenotype, with greater activity compared with colistin (P < 0.05). Dynamically grown biofilms were less susceptible to ceftolozane/tazobactam with active biofilm reduction (≥1 log cfu/cm2) observed in 2/3 isolates. Hypermutability did not affect the antibiofilm efficacy of ceftolozane/tazobactam in either static or dynamic conditions when comparing PAO1 and PAOMS. Consistent with the activity of ceftolozane/tazobactam as a potent inhibitor of PBP3, dramatic impacts on P. aeruginosa morphology were observed.

Conclusions

Our data demonstrate that ceftolozane/tazobactam has encouraging properties in the treatment of P. aeruginosa biofilm infections, and its activity is not diminished against mucoid or hypermutable variants at the timepoints examined.
Threshold and Spatial Effects of Fiscal Policy on Business Cycle Synchronisation in the Economic Community of West African States
Authors: Diendere Louis-Joel B , Diendere Achille A , Eggoh Jude
Published: December 2024

This research analyses the threshold effects of fiscal policy on business cycle synchronisation in the Economic Community of West African States (ECOWAS). The main contribution is the analysis of the effects of respecting versus not respecting deficit and debt thresholds on the synchronisation of business cycles through the creation of binary variables. The study covers the period 1990–2020 and fourteen ECOWAS countries. The results show that the optimal pro-growth thresholds for the budget deficit and debt are 5.559% and 45.61% of GDP, respectively. Furthermore, spatial analysis reveals significant positive spatial spillover effects of respecting these thresholds on synchronising business cycles within ECOWAS. The current convergence criterion of −3% for the budget balance is favourable for growth and business cycle convergence. In addition, the current debt convergence criterion of 70% of GDP could be adjusted. Our results suggest the need to strengthen revenue mobilisation, harmonise taxation and improve the monitoring of fiscal standards.
Soybean isoflavone promotes milk yield and milk fat yield through the ERα-mediated Akt/mTOR pathway in dairy goats
Authors: Shao Yuexin , Huang Jiangtao , Wei Manhong , Fan Liaoyu , Shi Huaiping , Shi Hengbo
Published: December 2024

Soybean isoflavone (SIF) in soybeans are natural phytoestrogens, which is functioned as an estrogen agonistic or antagonistic. SIF regulates the capacity of animals to synthesize triacylglycerols by directly utilizing long-chain fatty acids. However, few studies have focused on its regulatory lipid metabolism in lactating dairy goats. The objective of this study was to investigate the influence of SIF on milk yield and composition using Saanen dairy goats as a model, employing both in vivo and in vitro approaches. In the in vivo phase, a total of 20 goats were randomly divided into 2 groups: the control group fed a basal diet, and the experimental group fed a basal diet supplemented with SIF at a dosage of 100 mg/d. The results underscored a significant elevation in serum estrogen and prolactin levels in the SIF-supplemented group (P < 0.05). Notably, SIF supplementation also displayed a higher milk fat percentage (P = 0.03). Transitioning to in vitro experimentation, the addition of SIF (75 µM) to goat mammary epithelial cells exhibited a pronounced effect on cell proliferation. It spurred cell proliferation and led to an increase in triacylglycerol levels (P < 0.05). Consistently, SIF showcased an enhancement in the expression of key genes associated with milk fat de novo synthesis. SIF demonstrated a rescuing effect on the suppressive impact of MK2206 on Akt protein phosphorylation. Importantly, the study observed that the knockdown of estrogen receptor alpha (ERα) expression completely counteracted the effect of SIF on lipid droplet accumulation. Collectively, the current study establishes the critical role of SIF in process of fatty acid de novo in the goat mammary gland. This regulation is notably mediated through the ERα-Akt axis, thus enriching our understanding of this intricate biological process. This research sheds light on the potential benefits of SIF supplementation in dairy goat farming, ultimately contributing to improved milk production and quality.
Management of multiple vertebral fractures during lactation in a patient with osteogenesis imperfecta type I following twin delivery
Authors: Ng Chrislyn , Trinh Anne , Zebaze Roger , Shore-Lorenti Cat , Ebeling Peter R , Milat Frances
Published: December 2024

Osteogenesis imperfecta (OI) is an uncommon bone disorder caused by mutations in type I collagen involved in bone matrix leading to increased fracture risk. There are several sub-categories within OI, with OI type I being the most common and mildest form. Women with OI considering pregnancy need to be aware of bone loss and fracture risk, particularly with lactation. We report the first case of a female with twin pregnancy and OI type I who presented with multiple vertebral fractures following delivery and postpartum lactation. Following endocrine review, she weaned breast-feeding but represented within weeks with further pain and magnetic resonance imaging (MRI) demonstrating new T12 and L1 fractures. Even after receiving intravenous zoledronic acid, she experienced further thoracic pain after lifting, and MRI demonstrated a further T7 fracture. Following modification of her treatment regimen to daily teriparatide injections for 12 months, repeat dual-energy X-ray absorptiometry scan showed a significant improvement in bone mineral density at the lumbar spine and left hip. Bone loss with lactation is an important consideration for women with OI considering pregnancy. Women with OI should be assessed by an endocrinologist prior to conception to optimize bone health and have an individualized plan to mitigate bone loss and fracture risk during pregnancy and the postpartum period.
Establishing Neurorights: New Rights versus Derived Rights
Authors: Istace Timo
Published: December 2024

The way in which neurotechnology interferes with the human mind by enabling reverse inferences of mental states and alterations of mental processes, is a source of significant concern. Both human rights scholars and international and regional human rights institutions are actively examining which human rights safeguards are needed to address these concerns and protect the human mind. Central to this exploration is the question of how human rights law should formally establish these safeguards: through the introduction of neurorights as new stand-alone human rights, or by deriving neurorights form existing rights? This article seeks to contrast arguments in favour and against both strategies, to inform a substantiated choice for the preferable option. To this end, the article will first outline the origins of the neurorights debate. Subsequently, it will elaborate on the two identified approaches to establishing neurorights. Thereafter, both approaches will be assessed on their merits, focussing on the general criteria of ‘need’ and ‘feasibility’. Based on this evaluation, the article identifies the Derivation Approach as the preferable path forward. The need for new, stand-alone rights is insufficiently established, whereas deriving neurorights from existing rights provides clearer and more coherent safeguards, and encounters fewer political challenges.
The value of a nomogram based on 18F-FDG PET/CT metabolic parameters and metabolic heterogeneity in predicting distant metastasis in gastric cancer
Authors: Zhang Guanjie , Shi Aiqi , Ding Xiaofang , Wang Jianlin
Published: December 2024

Objective

To investigate the value of metabolic parameters and metabolic heterogeneity from pretreatment deoxy-2-[fluorine-18]-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting distant metastasis in gastric cancer.

Methods

Eighty-six patients with pathologically confirmed gastric adenocarcinoma were included in this study. All patients underwent a whole-body 18F-FDG PET/CT scan before treatment. Clinicopathologic and imaging data were collected, including metabolic parameters such as maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary gastric cancer lesions. Heterogeneity index (HI)-1 was expressed as the absolute value of the linear regression slopes between the MTVs at different SUVmax thresholds (40% × SUVmax, 80% × SUVmax), while HI-2 was expressed as the difference between SUVmax and SUVmean. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. The correlation between the above parameters and distant metastasis in gastric cancer was analyzed using the training cohort. A nomogram prediction model was then established and later verified with the validation cohort. Finally, decision curve analysis was used to evaluate the clinical utility of the model.

Results

This study included 86 patients with gastric cancer, with 60 (69.8%) in the training cohort and 26 (30.2%) in the validation cohort. There was no significant difference in the balanced comparison between both cohorts (all P > .05). Among all patients, 31 (36.0%) developed distant metastasis, while 55 (64.0%) did not. In patients who developed distant tumor metastasis, carcinoembryonic antigen, carbohydrate antigen (CA)12–5, CA19–9, CA72–4, MTV, TLG, and HI-1 were significantly higher than in patients without distant metastasis (all P < .05). Multivariate logistic regression analysis identified CA72–4 (OR: 1.151, 95% CI: 1.020–1.300, P = .023) and HI-1 (OR: 1.647, 95% CI: 1.063–2.553, P = .026) as independent risk factors for predicting distant metastasis in gastric cancer. The nomogram constructed from this analysis exhibited high predictive efficacy in the training (AUC: 0.874, 95% CI: 0.766–0.983) and validation (AUC: 0.915, 95% CI: 0.790–1.000) cohorts, providing a net clinical benefit for patients.

Conclusion

HI-1 is an independent risk factor for predicting distant metastasis in gastric cancer. A comprehensive prediction model combining HI-1 with the tumor marker CA72–4 can increase the net clinical benefit for patients.
Protection From COVID-19 Vaccination and Prior SARS-CoV-2 Infection Among Children Aged 6 Months–4 Years, United States, September 2022–April 2023
Authors: Feldstein Leora R , Ruffin Jasmine , Wiegand Ryan , Grant Lauren , Babu Tara M , Briggs-Hagen Melissa , Burgess Jefferey L , Caban-Martinez Alberto J , Chu Helen Y , Ellingson Katherine D , Englund Janet A , Hegmann Kurt T , Jeddy Zuha , Kuntz Jennifer , Lauring Adam S , Lutrick Karen , Martin Emily T , Mathenge Clare , Meece Jennifer , Midgley Claire M , Monto Arnold S , Naleway Allison L , Newes-Adeyi Gabriella , Odame-Bamfo Leah , Olsho Lauren E W , Phillips Andrew L , Rai Ramona P , Saydah Sharon , Smith Ning , Tyner Harmony , Vaughan Molly , Weil Ana A , Yoon Sarang K , Britton Amadea , Gaglani Manjusha
Published: December 2024

To understand how coronavirus disease 2019 vaccines impact infection risk in children <5 years, we assessed risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from September 2022 to April 2023 in 3 cohort studies. There was no difference in risk by vaccination status. While vaccines reduce severe disease, they may not reduce SARS-CoV-2 infections in naïve young children.
It’s about time: revisiting reciprocity and triadicity in relational event analysis
Authors: Juozaitienė Rūta , Wit Ernst C
Published: December 2024

Societies are intricate systems comprising interdependent social actors interconnected through diverse relationships. It has long been recognized that reciprocity and triadic closure are two fundamental components of this interdependence, and have as such been included in social network models. However, computational limitations and modelling complexity have meant that reciprodicity and triadic closure statistics included in such models have necessarily been simplified. Using novel computational and modelling approaches in relational event analysis, the aim of this paper is to explore a spectrum of endogenous network effect definitions, ranging from straightforward binary variables to complex, temporal functions accounting for the diminishing relevance of past events. Through simulation studies and real-world dataset analyses, it highlights the importance of comprehensively considering temporal dynamics and subtle assumptions in defining network effects. Neglecting these aspects can lead to significant pitfalls in the analysis. Fundamentally, the paper highlights the time-varying nature of reciprocity and triadic closure effects evident in empirical datasets. While exponential decay functions sometimes capture their temporal structure, more complex continuous functions of time often describe the intricate structure of both effects more precisely.
(009) ERECTION DURATION, FREQUENCY AND FIRMNESS: A DESCRIPTIVE ANALYSIS FROM A POPULATION-BASED STUDY USING A WEARABLE PENILE RING
Authors: Saffati G , Orozco Rendon D , Daily R , Khera M , Mulhall J
Published: December 2024

Introduction

Erectile function is a crucial aspect of male sexual health and well-being, influenced by various physical and psychological factors. Traditional assessment methods have relied heavily on subjective self-reports and laboratory-based techniques, which often fail to capture the full scope of erections in real-world settings. The emergence of wearable penile ring devices marks a significant advancement, enabling continuous, objective monitoring of erections in naturalistic environments.

Objective

This study aims to synthesize data collected from the FirmTech TechRing, a wearable penile ring device, and analyze the typical attributes of nocturnal erections.

Methods

The study employed a cross-sectional design, with data collected from July 2023 to June 2024. All patients who utilized the FirmTech TechRing for a minimum of four hours per night during this period were included. The device measures erection frequency, rigidity, and duration through embedded sensors. De-identified data were analyzed using descriptive and inferential statistical methods to assess typical attributes of nocturnal erections.

Results

A total of 774 participants were included, encompassing a total of 4653 recorded observations. The median recording duration was 7.75 hours (IQR: 6.67, 8.82 hours). Analysis revealed a total of 12 581 erections, with a median duration of 36.2 minutes (IQR: 22.0-57.8 minutes), as summarized in Fig. 1. Participants experienced a median of 2.72 erections (IQR: 2.0-3.5) per recording, with a median firmness score of 4.69 on a scale of 1 to 10 (IQR: 3.28-7.02). These findings align closely with previously reported ranges, underscoring the validity of the data obtained from penile ring devices.

Conclusions

This study offers an unprecedented glimpse into the objective characteristics of male erections in naturalistic settings. By leveraging the capabilities of wearable technology and objective data collection, researchers and clinicians can continue to unravel the complexities of penile physiology and develop more effective strategies for the prevention, diagnosis, and management of erectile dysfunction and other sexual health concerns.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: FirmTech.
(019) CONTEMPORARY FINDINGS REGARDING THE EFFICACY AND SAFETY OF THE “DRAIN AND RETAIN” MANEUVER FOR UROLOGIC PROSTHETIC RESERVOIRS DURING INFLATABLE PENILE PROSTHESIS REVISION SURGERY
Authors: Pereira TA , Rust JO , Good J , Alverman TA , Barham D , Egemba C , Gross MS , Hammad M , Hsieh M , Huynh A , Lentz AC , Nose B , Simhan J , Yafi F , Bernie HL
Published: December 2024

Introduction

Urologic prosthetic reservoirs (UPR) can become firmly adherent to surrounding structures, and their removal during revision surgeries carries significant risks. Over the last decade, the “drain and retain” maneuver has been increasingly implemented to safely leave decommissioned UPRs in place. The utility and safety of this technique have not been further explored in the literature following the original descriptive publications.

Objective

We sought to update the efficacy and safety of the “drain and retain” maneuver by analyzing a contemporary multi-institutional cohort.

Methods

Patients who underwent inflatable penile prosthesis (IPP) surgery at seven busy penile implant centers in the United States between July 2016 and June 2024 were reviewed. We compared patients who underwent revision IPP surgery and subtotal device removal with “drain and retain” to those who had complete component removal and exchange. Explant cases for infection and revision cases using the original UPR were excluded. Postoperative complications and infection rates were evaluated and compared to patients receiving primary IPP surgery as a control group.

Results

1201 primary IPP cases and 231 revision cases were included. Among the revision cases, 112 (48.5%) utilized the "drain and retain" technique, while 119 (51.5%) involved complete reservoir removal. Patient demographics are listed in Table 1. There were no statistically significant differences in postoperative infection rates (p = 0.897) among the groups (Table 2). Similarly, there were no statistically significant differences in postoperative infections when stratified by different prosthesis types (p = 0.987). Regarding non-infections complications, there were no significant differences between the “drain and retain” group compared to revision cases where all components were removed. (p = 0.393) (Table 3).

Conclusions

To our knowledge, this is the most extensive study assessing the safety of leaving UPR in place during IPP revision surgery. The "drain and retain" strategy is a safe approach for IPP revision surgery. It avoids the potential morbidity of dissection into the retropubic space while maintaining infection and complication rates comparable to primary IPP cases.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific; Coloplast; BK Ultrasound.
(035) EFFICACY AND SAFETY OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM TREATMENT IN PATIENTS WITH VENTRAL PENILE PLAQUES
Authors: Saffati G , Orozco Rendon D , Hinojosa-Gonzalez DE , Kronstedt S , Miller JA , Moukhtar Hammad MA , Yafi FA , Angulo-Llanos L , Garret GM , Sandler MD , Tran DV , Masterson TA , Raheem O , Khera M
Published: December 2024

Introduction

Peyronie's disease (PD) is an acquired connective tissue disorder characterized by the formation of fibrous plaques within the tunica albuginea of the penis. Previous studies have demonstrated the efficacy and safety of Collagenase Clostridium Histolyticum (CCH) injections for the treatment of PD; however, few of these studies analyzed the impact of plaque location on treatment outcomes.

Objective

This study aimed to evaluate the efficacy and safety of CCH injections for the treatment of PD in patients with ventral penile plaques.

Methods

This study was approved by our Institutional Review Board, and is a multi-center, retrospective study investigating those who received CCH injections for the treatment of PD. Clinical and demographic data were extracted from patients' medical records. The study included only those patients who received CCH injections. Patients were stratified by plaque location. Main outcomes were adverse events from CCH (bruising, swelling, pain, hematoma, penile fracture, loss of length, new erectile dysfunction (ED)), satisfaction, change in curvature, and conversion to surgery after CCH treatment.

Results

In total, 550 patients met inclusion criteria. Among them, 54 patients had a ventral plaque, while the remaining 496 patients had a non-ventral plaque. Mean age of the ventral plaque cohort was 57.55 ± 11.08 years, compared to 56.52 ± 9.14 years in the non-ventral plaque group. There was no significant difference in change in penile curvature between ventral and non-ventral plaques, with a mean change of 27.76 ± 21.3 degrees vs 22.66 ± 18.55 degrees, p = 0.13, respectively. Patients with ventral plaques were more likely to experience newfound ED compared to patients without ventral plaques (p = 0.001). No significant difference was found for other side effects experienced between the two cohorts (Table 1).

Conclusions

CCH injections significantly improved penile curvature in both ventral and non-ventral plaque groups, with no significant difference in the rate of side effects between these two groups.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Disclosures: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast, Halozyme Investor: Sprout.
(041) IN CLINIC VERAPAMIL INJECTIONS FOR PEYRONIE’S DISEASE: A RETROSPECTIVE STUDY ON PATIENT SEXUAL SATISFACTION
Authors: Campbell J , Mcmartin C , Ory J , Power L , Patel P
Published: December 2024

Introduction

Peyronie’s disease (PD) is an acquired curvature of the penis that affects 5-10% of men and is associated with psychological distress. Intralesional Clostridium collagenase (Xiaflex) and interferon have been removed from Canada, leaving verapamil as the only effective therapy available to our patients. The results of intralesional verapamil (ILV) are variable depending on dosing, injection protocols, and practitioner technique. Surgical treatment of PD endorses substantial risk of penile length loss and erectile dysfunction, which most patients prefer to avoid.

Objective

We aimed to evaluate our experience with ILV to determine whether off-label ILV provides satisfactory results to men with PD and avoids more invasive interventions.

Methods

This is a retrospective multicenter cohort study of 224 men who completed ILV treatment between January 1st 2021 and December 31st 2023 performed by three urologists. Dorsal penile block was performed, and verapamil was injected using FAN technique into PD scar. Subjective clinical data was retrieved from initial consultation and follow-up visits through our electronic records.

Results

Mean age was 57 years old, with a majority of men having an upward curvature (56.7%) between 30-45° (43.8%). Mean onset of the curvature was 20.5 months before the initial consult, with a disease stability of 11.3 months. Risk factors including erectile dysfunction (44.2%), diabetes (19.1%) and active smoking (20.6%) were evaluated. The curvature was initially impairing sexual intercourse for 59% of patients. After ILV treatment protocol, 81.3% of patient’s curvature were subjectively improved, with 94.6% of men being able to engage in sexual intercourse, an increase of 35.6%. Only 14.3% required subsequent surgical treatment for their PD.

Conclusions

We conclude that our ILV treatment protocol helps men regain their ability to engage in sexual intercourse, provides a subjective lesser degree of curvature and reduces the need to undergo more invasive interventions.

Disclosure

No.
(044) ASSESSING THE EFFICACY OF INTRAURETHRAL BIMIX GEL AS AN ADJUNCT THERAPY IN 55 ERECTILE DYSFUNCTION PATIENTS
Authors: Cruz J , Farias A , Defauwes N , Prabhakar P , Martinez D , Caso J
Published: December 2024

Introduction

Erectile dysfunction can affect men from ages 40 to 70, with a range of 30% to 50% of the population experiencing this inability to achieve and sustain an erection (1). Erectile dysfunction can have a myriad of problems with risk factors such as obesity, smoking, and age, to name a few. The traditional treatments for ED are oral therapy, injections, and penile prostheses, but in some cases, these may not be effective.

Objective

To evaluate the effectiveness of intraurethral Bimix gel as an adjunct to therapy in 56 patients diagnosed with ED.

Methods

A retrospective chart review of patients who were prescribed intraurethral Bimix gel for a diagnosis of ED as an adjunct following primary therapy were selected. This yielded a total of 55 patients with a mean age of 61 (range, 25-85) years. The patients were prescribed intraurethral Bimix gel because of their unsatisfactory response to oral therapy. The efficacy of the gel was evaluated by comparing the Sexual Health Inventory for Men (SHIM) scores before and after the treatment with a Wilcoxon signed rank test.

Results

The mean SHIM score prior to intraurethral Bimix gel was 9.62 (range, 0-24), and following the Bimix gel administration was 11.93 (range, 1-25) (p < 0.001). The patients had a favorable response to the intraurethral Bimix gel therapy. This therapy offers a good alternative to patients and an easier mode of administration for patients who are wary of intracavernosal injections. One of the common side effects reported was a mild burning sensation at the administration site during the application and absorption period. There were no other adverse effects.

Conclusions

Intraurethral Bimix gel is a good alternative adjunct to primary oral therapy for erectile dysfunction which can be used together with the initial therapy or as a booster during the act of sexual intercourse as a salvage option. References 1. Khera, M., & Goldstein, I. (2011). Erectile dysfunction. BMJ Clinical evidence, 2011.

Disclosure

No.
(074) OFFICE-BASED MICRODISSECTION TESTICULAR SPERM EXTRACTION FOR NONOBSTRUCTIVE AZOOSPERMIA RESULTS IN HIGH SPERM RETRIEVAL RATES
Authors: Seyer A , Walker D , Ainsworth A , Shenoy C , Babayev S , Stewart E , Khan Z , Zhao Y , Helo S
Published: December 2024

Introduction

Microdissection testicular sperm extraction (microTESE) is performed in men with nonobstructive azoospermia who desire sperm retrieval for use in IVF. This procedure can be performed in the operating room or in the clinic with local analgesic.

Objective

To report office-based microTESE sperm retrieval, fertilization, and livebirth rates.

Methods

A review was conducted of all patients who underwent office-based microTESE for nonobstructive azoospermia with a partner that who underwent concurrent oocyte retrieval for an intended in-vitro fertilization (IVF) intracytoplasmic injection (ICSI) cycle 2022-2024. All male partners underwent Y chromosome microdeletion testing, karyotype analysis, and hormonal testing preoperatively. Patients with a diagnosis of hypogonadism were offered medical therapy and those diagnosed with a varicocele were offered varicocelectomy prior to microTESE. Office-based microTESE was performed using a surgical operating microscope, spermatic cord block, and oral anxiolytic. Female partners underwent oocyte retrieval with oocyte cryopreservation prior to microTESE. Oocyte warming and ICSI was performed only following the collection of motile sperm from the fresh microTESE samples. Relevant demographic and clinical data were collected for patients and their partners. Descriptive data analysis was performed and reported as mean ± standard deviation.

Results

Ten patients underwent 11 office-based microTESE procedures. One patient had repeat microTESE following an unsuccessful IVF/ICSI cycle. Overall sperm retrieval rate was 70% for first time microTESE with mean search time 197.2 ± 96.5 min. Amongst couples with successful sperm retrieval, normal fertilization rate was 42%. Early cleavage arrest was seen in 84% of normally fertilized oocytes with a 16% blastocyst rate. Embryo development arrested entirely in two couples, while the remaining five couples had at least one blastocyst on day 5 and underwent embryo transfer. Of these, four resulted in a clinical pregnancy (36%). Three couples had a successful live birth and one has an ongoing pregnancy with ultrasound-confirmed fetal heartbeat.

Conclusions

Our small series demonstrates high sperm retrieval rates from office-based microTESE. Fertilization rates, clinical pregnancies and live birth rates are comparable with those reported in the literature. Given the financial cost associated with microTESE and IVF/ICSI for nonobstructive azoospermia patients, office-based microTESE may be a solution to make the process more financially accessible for couples.

Disclosure

No.