bluuebunny/crossref_metadata_2025 huggingface dataset:
(249) SHORTER DURATION OF POSTOP IPP INFLATION FOLLOWING MANUAL MODELING MAY LEAD TO CURVATURE REGRESSION
Authors: Gross BL , Gross MS , Madden-Fuentes RJ
Published: December 2024

Introduction

Patients with concomitant erectile dysfunction (ED) and PD are best served by insertion of an inflatable penile prosthesis (IPP) in order to adequately treat both conditions. We elect to leave the IPP inflated postoperatively to maintain curvature reduction improvements, but the ideal duration of postoperative inflation for this purpose has not been determined. There is also little data regarding how the duration of postoperative IPP inflation may affect penile curvature.

Objective

The primary objective was to evaluate how the duration of post-operative IPP inflation may impact changes in penile curvature.

Methods

All IPP patients with known preoperative penile curvature undergoing IPP placement by a single surgeon from January 2017 to June 2023 were included in this IRB-approved (IRB 00031589) retrospective series. All patients received a 3-piece Coloplast Titan Touch IPP (Coloplast, Minneapolis, MN, USA). Goniometer was used to assess curvature during preoperative intracavernosal injection and duplex Doppler ultrasound. All patients followed a standard postoperative follow-up protocol of visits at 2 weeks, 6 weeks and 6 months, although some were also seen sooner than anticipated or with additional unplanned follow-up. Our practice is to leave the device partially (to 60-70%) inflated for2 weeks postoperatively and perform device teaching at 6 weeks postoperatively if feasible. Patients who cannot tolerate device inflation due to pain or other extenuating circumstances are deflated earlier than two weeks. The change in penile curvature, as determined by goniometry at various timepoints, was evaluated relative to the duration of IPP inflation postoperatively.

Results

Sixty-one patients were included. The average preoperative penile curvature was 40° ± 16° (0° to 80°). At the time of surgery, all IPPs were left inflated on average 11 ± 5.2 days with device deflation at <2 weeks for 31.3% patients (n = 19) and at ≥2 weeks for 68.9% patients (n = 42). There was no curvature regression for either group at 2 weeks or 6 months; however, both groups had a subset of patients with worsened curvature at 6 weeks. Penile curvature was worse at 6 weeks for 26.3% (n = 5) of patients with a shorter IPP inflation period compared to 12.8% (n = 5) of patients with device inflation of at least two weeks.

Conclusions

Patients with IPP deflation <2 weeks had a higher incidence of curvature regression 6 weeks postoperatively compared to patients with IPP deflation ≥2 weeks. Curvature did not regress while device was inflated or between the 6 week and 6 month postoperative visits. Additional studies are needed to elucidate the optimal timeframe for, and degree of, IPP inflation to avoid postoperative penile curvature regression.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, MenMD.
(251) ATYPICAL HORMONAL PROFILE AND POST-TREATMENT SEXUAL HEALTH CHALLENGES IN A YOUNG PATIENT WITH NON-SEMINOMATOUS TESTICULAR GERM CELL CARCINOMA
Authors: Souza L , Sousa L , Freire M , Moura D , Araujo F , Barretto N
Published: December 2024

Introduction

Non-seminomatous testicular germ cell carcinoma (NSTGCC) is a complex pathological entity known for its aggressiveness and metastatic potential, primarily affecting young men. The association of this tumor with specific hormonal changes, such as abnormal testosterone levels, underscores the importance of detailed evaluations in these patients.

Objective

To describe a case of a young patient who exhibited an atypical hormonal profile with elevated testosterone levels before a surgical intervention for NSTGCC, but post-treatment, despite normal testosterone levels, reported abnormal sexual quality of life.

Methods

This case study involved a detailed review of the patient’s medical history, physical examinations, laboratory analyses of hormones (Testosterone, LH, FSH), imaging (testicular ultrasound), and histopathological findings from the tumor after a left unilateral radical orchiectomy. Additionally, a literature review was conducted to compare these findings with existing reports, focusing on NSTGCC and its association with hormonal changes, as well as clinical management post-oncological treatment.

Results

Before surgical intervention, the patient exhibited an atypical hormonal profile with elevated testosterone levels (1556.51 ng/dL) and suppressed LH and FSH, without using exogenous testosterone. Post-orchiectomy and chemotherapy, LH and FSH levels normalized, and testosterone levels decreased to normal (495.0 ng/dL). Post-treatment, the patient experienced normal testosterone levels but reported erectile dysfunction and a significant reduction in quality of life. Considering the patient prior sperm cryopreservation and the urgent need to address changes in his sexual health, treatment with exogenous testosterone (deposteron 200 mg, one intramuscular ampoule every 14 days) was initiated. The patient now reports improved sexual quality of life and satisfaction with the therapeutic effects.

Conclusions

This case highlights the complexity of NSTGCC and the critical role of monitoring hormonal levels before and after treatment. The normalization of hormonal levels post-treatment underscores the necessity for individualized management, as these results do not always correlate with the patient’s quality of life, thereby optimizing therapeutic and prognostic outcomes. It also emphasizes the need for further studies on the clinical management of NSTGCC patients to enhance existing procedures and improve their quality of life and psychosocial well-being.

Disclosure

No.
(270) WORLDWIDE INTEREST IN TESTOSTERONE REPLACEMENT THERAPY
Authors: Lumbiganon S , Hammad M , Abou Chawareb E , Azad B , Miller J , Lee J , Yafi F
Published: December 2024

Introduction

Testosterone replacement therapy (TRT) has garnered substantial attention in recent years as a potential solution to various health concerns associated with low testosterone levels. TRT addresses symptoms ranging from low energy and libido to muscle loss and mood disturbances. Interest in TRT varies across different geographical regions, and comprehending these distinctions may assist healthcare providers in tailoring the appropriate use of TRT.

Objective

This study aims to assess global interest in testosterone replacement therapy and explore its correlation with available health-related and socioeconomic data.

Methods

Google Trends was employed to gauge online-based public interest in TRT. The data from various countries were ranked and compared using correlation statistics with health-related and socioeconomic data from the World Health Organization and the World Bank.

Results

Interest in TRT, as indicated by Google Trends, has experienced a consistent increase over the past five years. The top five countries with the highest levels of interest were the United States, Australia, Canada, New Zealand, and the United Kingdom, respectively. Positive correlations were identified between the rank of TRT interest for each country and government healthcare expenditure (R = 0.517, 95%CI; 0.211, 0.731) as well as gross domestic product per capita (R = 0.581, 95%CI; 0.286, 0.776). However, there was no significant correlation between TRT interest and population life expectancy (R = 0.229, 95%CI −0.130, 0.535), the percentage of the population with internet accessibility (R = 0.225, 95%CI; −0.102, 0.555), density of medical doctors per population (R = 0.096, 95%CI; −0.261, 0.430), or the WHO universal health coverage index (R = 0.314, 95%CI; −0.039, 0.598).

Conclusions

The analysis reveals a rising trend of interest in TRT, particularly in countries with higher GDP and greater government healthcare expenditure. This heightened interest may be attributed to improved economic status and increased healthcare spending. These findings can inform healthcare policy implementation based on each country’s income level and facilitate the monitoring of inappropriate TRT usage within individual countries.

Disclosure

No.
(282) IN THE EYES OF PATIENTS COMPLAINING OF PREMATURE EJACULATION, WHAT ARE THE NORMAL INTRAVAGINAL EJACULATION LATENCY TIME (IELT) AND EXPECTED IELT?
Authors: Wang C , Colonnello E , Sansone A , Zhang H , Zhu D , Jannini EA , Zhang Y
Published: December 2024

Introduction

Although the normal intravaginal ejaculation latency time (NIELT) in the eyes of patients with premature ejaculation (PE) and expected intravaginal ejaculation latency time (EIELT) are critically influential in the treatment of patients with PE, there is a significant dearth of exploratory research on these clinical parameters among patients with PE.

Objective

To explore the NIELT and EIELT of patients with PE, understand why patients with PE perceive such a long IELT as normal, and identify factors associated with EIELT.

Methods

We recruited both patients with PE and controls and administered questionnaires to gather data relevant to the research objectives.

Results

A total of 592 individuals (mean age 29.6 ± 6.2) were included in the study, comprising 466 patients with PE (mean age 28.3 ± 5.4) and 126 controls without PE (mean age 34.6 ± 6.5). The actual perceived IELT (PIELT), NIELT, and EIELT of patients with PE were 1.0 (1.0–2.0), 14.0 (10.0–15.0), and 15.0 (10.0–20.0), respectively, with a p-value <0.001. Among patients with PE, 51.3% expressed a NIELT >10 minutes, identical to the EIELT in a higher percentage (59.4%). Reasons why patients with PE perceived such long IELT as normal included self-perception (42.5%), online sources (21.0%), advice from friends (11.4%), information from sexual partners (8.2%), exposure to pornography (7.5%), and other sources (9.4%). Among various factors, NIELT accounted for the greatest extent of variability in EIELT (beta = 0.817, P < 0.001).

Conclusions

Patients with PE often have excessively high expectations regarding IELT, primarily due to their insufficient understanding of IELT. Sexual health care providers should provide comprehensive sexual education to patients with PE and strive to normalize their expectations of IELT, thereby enhancing their satisfaction with treatments, which is still a significant problem in PE management. Furthermore, the dissemination of these research findings to the public can promote a correct understanding of IELT, aligning people’s expectations with reality and mitigating sexual disappointment.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: EAJ is or has been paid consultant and/or paid speaker for Bayer, Ibsa, Menarini, Otsuka, Pfizer, Viatris.
(304) CORRELATION BETWEEN PENILE STRETCH LENGTH AND ERECT LENGTH OF VIETNAMESE MEN: A PROSPECTIVE STUDY
Authors: Ho P , Nguyen AT , Pham TMH , Nguyen THT , Pham MN , Nguyen THH
Published: December 2024

Introduction

Erect penis length plays an important role in the sexual confidence and sexual life of men. However, there was some difficulty in measuring the exact erection length while doing the clinical examination. Men who come for examination at our hospital in Vietnam are diverse in ages, geographical areas, and occupations. Clinical examination of male genitalia includes the penis and testicles as the two most important components. During the penile examination, assessment of the patient’s penis length at the time of examination reflects characteristics related to fertility and sexual function and contributes to diagnosis and prognosis. Moreover, there have not been many studies on penis size that fully evaluate measurements of flaccid, stretched, and erection. There were some studies about the average erect penile length in Europe and America, but there are have been no study studies in Vietnamese in recent years. In clinical practice, we also use stretch penile length to evaluate the erection length indirectly, but is there a correlation between them in the Asian men group or our report Vietnamese men?

Objective

To determine the correlation between penile length measured when stretched and erection.

Methods

Three hundred eight men who visited our hospital in Hanoi, Viet Nam were involved in our study between December 2022 and December 2023. The age, geographical areas, and occupations of the subjects were recorded. Penile measurements (flaccid, erect length, stretched length) were predominantly taken by one investigator using a tape measure and the same measurement technique. STATA version 17.0 was used for statistical evaluation of the results. Results were evaluated using descriptive statistics and Pearson correlation analysis between penile flaccid, erect length, stretched length parameters, p value less than 0.05 was considered significant.

Results

The mean age of the subjects was 28 (range: 15-55) years. Men from big urban areas (Ha Noi, Hai Phong, Ho Chi Minh City) had the most visits (29,9%). Nearly 3% of participants had circumcision. It accounted for 55,2% of freelancers and businessmen who were consulted. The mean penile length in flaccid, stretched and erection states were 9.41 ± 1.75 cm, 12.75 ± 1.73 cm, and 13.43 ± 1.53 cm, respectively. Mean penile length were not significantly different between ages, geographical area, and occupation (p > 0.05). There was a positive correlation between stretch length and erection length (r = 0.73, p < 0.05); with the equation of erect length = 13.34 + 0.01x stretched length.

Conclusions

Our study provides fully evaluate measurements of flaccid, stretched, and erection in Vietnamese men and there was a positive correlation between stretch length and erection length. So we suggest using stretch penile length to evaluate erection length in our clinical practice.

Disclosure

No.
Contribution of the main contaminating materials during pig slaughter to the microbial numbers on carcasses
Authors: Tholen Janna , Upmann Matthias
Published: December 2024

During pig slaughter, contaminants such as intestinal and stomach contents, bile, tubular rail fat, and reddish foam from the respiratory tract frequently appear on carcasses, potentially compromising meat safety. This study examined the impact of these contaminants on the bacterial loads of pig carcasses, using total bacterial counts and Enterobacteriaceae counts as hygiene indicators. Examination of the substances as such showed that intestinal and stomach contents were particularly conspicuous to undermine the carcase hygiene due to total bacterial counts of ∼6.0 log10 CFU g−1 (intestinal content) and 5.5 log10 CFU g−1 (stomach content). Tubular rail fat showed varying contamination levels, from low (3.1 log10 CFU g−1) to high (6.4 log10 CFU g−1). The reddish foam had moderate contamination (4.3 log10 CFU g−1). Enterobacteriaceae levels mirrored these results at a lower level. Subsequently, a comparative study analysing bacterial levels in contaminated and in noncontaminated pork rind regions was performed. Even small amounts of intestinal and stomach contents led to significant increases in total bacterial counts of up to 3 log10 CFU cm−² and in Enterobacteriaceae counts (up to 5 log10 CFU cm−²). Other contaminants did not significantly raise bacterial levels: their total viable counts around 3.5 log10 CFU cm−² were similar to those of uncontaminated carcass areas. Nevertheless, they should be removed before further processing.
Modulation of physiological functions and metabolome of Vibrio alginolyticus by quorum-regulatory sRNA, Qrr1
Authors: Zhao Yanni , Wu Ruobing , Wu Xuan , Zhou Ningning , Ren Jiamin , Liu Wang , Yu Rui , Zhang Senhu , Yang Jinfang , Li Hua , Liu Huan
Published: December 2024

Vibrio alginolyticus, the causative agent of aquatic vertebrates and invertebrates, can cause severe infections (e.g. septicemia, gill necrosis, and surface ulcers) and high mortality in aquatic organisms, leading to serious economic losses in global aquaculture. Small non-coding RNAs (sRNAs), emerging modulators of gene expression, played vital regulatory roles in virulence, pathogenicity, and physiological metabolism of bacteria. In this work, the modulation of physiological functions and metabolome of V. alginolyticus by the quorum-regulatory sRNA, Qrr1, was figured out. We found that the deletion of qrr1 induced significant cell shape elongation. Meanwhile, Qrr1 could inhibit the production of alkaline serine protease by weakening the expression of main regulator LuxR in the quorum sensing (QS) system. Moreover, the untargeted metabolomics and lipidomics approaches showed that most of nucleotides, organic acids, carbohydrates, and lipidome (both lipid content and category) were significantly altered in response to the qrr1 deletion. Spearman correlation analysis demonstrated that most of the intermediates involved in glutamate metabolism, sphingolipid metabolism, and glycerolipid metabolism displayed high correlations with cell virulence factors. These findings illuminate the mechanism of bacterial virulence regulation and further exploit potential therapeutic targets for virulence prevention in V. alginolyticus.
Introduction
Authors: Derham Rory
Published: December 2024

This chapter introduces the key concept of set-off. Despite the difficulty of a comprehensive definition without reference to the various forms it takes, a set-off is generally defined as the setting of money cross-claims against each other to produce a balance. Additionally, set-off provides a defence to an action, although, depending on the form of set-off, the issue need not arise in that context. The chapter then elaborates on the importance of set-off that revolves around insolvency, counterclaims, costs, third party interests, and arbitration. It then details the forms of set-off and civil procedures rules as per the Civil Procedure Rules 1998
Mutuality: Introduction
Authors: Derham Rory
Published: December 2024

This chapter provides an overview of mutuality. It highlights that, under the Statutes of Set-off, there must be mutuality for both insolvency set-off and set-off. Essentially, mutuality does not require that the claims should arise at the same time, nor that there should be any connection between them. However, claims may have a different nature since the notion of mutuality conveys reciprocity instead of correspondence. Additionally, mutuality needs commensurable cross-demands between the same parties and that they are held in the same capacity, right, or interest. The chapter examines the general principles of equitable interests and the correlation of mutuality to set-off under the Statutes of Set-off.
Mutuality: Same Right
Authors: Derham Rory
Published: December 2024

This chapter explains the requirement that the demands be held in the same right in the case of insolvency set-off. It cites that each of the parties to a proposed set-off must be both personally liable to the other and the beneficial owner of a cross-demand against the other. The Statutes of Set-off contemplate mutuality as reference to the legal title of the debts. However, equity may allow a set-off by analogy with the Statues if there is mutuality in equity but not in law. The chapter considers the requirement of mutuality in correlation with personal capacities, trustees in bankruptcy, and the effect of company liquidation.
Combination of Bank Accounts
Authors: Derham Rory
Published: December 2024

This chapter discusses the circumstances wherein a customer has more than one account with a bank. It highlights the bank’s power to combine, or consolidate, the accounts and proceed on the basis that there is only one debt for the balance. Combination is important if the bank is suspicious of the customer’s solvency because it provides the bank with a means to obtain the benefit of the account in credit, by setting it against the debit account before the customer dissipates the credit balance. The chapter then provides an overview of the nature of the right of combination. It also considers the criticisms surrounding the combination since it was considered to be inconsistent with many of the features of bank accounts.
Chemically peculiar stars as members of open clusters
Authors: Faltová N , Jadlovský D , Kueß L , Labaj M , Mesarč M , Mondal P , Neumannová K , Paunzen E , Prišegen M , Ramezani T , Supíková J , Svačinková K , Szász G , Vítková M , Xia C
Published: December 2024

The chemically peculiar (CP) stars of the upper main sequence are excellent astrophysical laboratories to test the diffusion, mass-loss, rotational mixing, and pulsation in the (non-)presence of a stable local magnetic field. These processes are time-dependent. The age estimation of Galactic field stars suffers from several limitations. Therefore, studying members of star clusters overcomes these difficulties. We matched the most recently published catalogues of star clusters and CP stars. For the matching, we used the newest Gaia Data Release. We also used the $\Delta$a photometry tool to further distinguish between the CP subgroups. We found 595 CP stars in 408 star clusters of all ages. Furthermore, we report on misclassified metallic line stars (Am or CP1) and objects with no CP classification. The distribution of magnetic and non-magnetic CP stars on the main sequence seems different. We do not detect very young and very old CP stars showing rotationally induced variability. CP members of star clusters help to study all relevant processes responsible for this phenomenon in more detail. Still, a larger sample is desired to put tighter constraints on models.
Metallicity of RR Lyrae stars from the Gaia Data Release 3 catalogue computed with Machine Learning algorithms
Authors: Muraveva Tatiana , Giannetti Andrea , Clementini Gisella , Garofalo Alessia , Monti Lorenzo
Published: December 2024

We present new $P -\phi _{31}-{\rm [Fe/H]}$ and $P -\phi _{31}- A_2 - {\rm [Fe/H]}$ relations for fundamental mode (RRab) and first-overtone mode (RRc) RR Lyrae stars (RRLs), respectively. The relations were calibrated based on pulsation periods and Fourier parameters of the RRL light curves in the GaiaG-band published in the Gaia Data Release 3 (DR3), and accurate spectroscopically measured metallicities available in the literature. We apply the feature selection algorithm to identify the most relevant parameters for the determination of metallicity. To fit the relations, we used the Bayesian approach, which allowed us to carefully take into account uncertainties in various parameters and the intrinsic scatter of the relations. The root mean squared errors of the predicted metallicity values in the training samples are 0.28 and 0.21 dex for RRab and RRc stars, respectively, comparable with the typical uncertainty of low/intermediate resolution spectroscopic metallicity measurements. We applied the new relations to measure individual metallicities and distances to $\sim$134 000 RRLs from the Gaia DR3 catalogue, as well as mean metallicities and distances to 38 Milky Way globular clusters. We also estimate the mean metallicity and distance to the Large Magellanic Cloud and Small Magellanic Cloud: ${\rm [Fe/H]_{LMC} = -1.63\pm 0.36}$ and $\mu _{\rm LMC}=18.55\pm 0.18$ mag, and ${\rm [Fe/H]_{SMC}=-1.86\pm 0.36}$ dex and $\mu _{\rm SMC}=19.01\pm 0.17$ mag, respectively, in excellent agreement with previous measurements.
The total mass of the close, double degenerate (DA+DQ) system NLTT 16249
Authors: Vennes Stéphane , Kawka Adela
Published: December 2024

We revisit the binary and stellar properties of the double-degenerate system NLTT 16249. An analysis of new echelle spectra, supported by a joint study of a DQZ velocity template NLTT 44303, confirms the orbital period and constrains the mass ratio revealing a carbon-polluted DQ white dwarf that is up to ${\approx} 6$ per cent more massive than its hydrogen-rich DA companion. Our new model atmosphere analysis of the DA and DQ components, constrained by an accurate Gaia parallax measurement that places the binary at a distance of 57.8 pc, reveals lower mass and temperature than previously estimated for both components, but with higher carbon and nitrogen abundances in the DQ atmosphere. The two components are nearly coeval and could have been generated following a single common envelope event.
Bgee in 2024: focus on curated single-cell RNA-seq datasets, and query tools
Authors: Bastian Frederic B , Cammarata Alessandro Brandulas , Carsanaro Sara , Detering Harald , Huang Wan-Ting , Joye Sagane , Niknejad Anne , Nyamari Marion , Mendes de Farias Tarcisio , Moretti Sébastien , Tzivanopoulou Marianna , Wollbrett Julien , Robinson-Rechavi Marc
Published: December 2024

Bgee (https://www.bgee.org/) is a database to retrieve and compare gene expression patterns in multiple animal species. Expression data are integrated and made comparable between species thanks to consistent data annotation and processing. In the past years, we have integrated single-cell RNA-sequencing expression data into Bgee through careful curation of public datasets in multiple species. We have fully integrated this new technology along with the wealth of other data existing in Bgee. As a result, Bgee can now provide one definitive answer all the way to the cell resolution about a gene’s expression pattern, comparable between species. We have updated our programmatic access tools to adapt to these changes accordingly. We have introduced a new web interface, providing detailed access to our annotations and expression data. It enables users to retrieve data, e.g. for specific organs, cell types or developmental stages, and leverages ontology reasoning to build powerful queries. Finally, we have expanded our species count from 29 to 52, emphasizing fish species critical for vertebrate genome studies, species of agronomic and veterinary importance and nonhuman primates.
ATAC and SAGA histone acetyltransferase modules facilitate transcription factor binding to nucleosomes independent of their acetylation activity
Authors: Chesnutt Kristin V , Yayli Gizem , Toelzer Christine , Damilot Mylène , Cox Khan , Gautam Gunjan , Berger Imre , Tora László , Poirier Michael G
Published: December 2024

Transcription initiation involves the coordination of multiple events, starting with activators binding specific DNA target sequences, which recruit transcription coactivators to open chromatin and enable binding of general transcription factors and RNA polymerase II to promoters. Two key human transcriptional coactivator complexes, ATAC (ADA-two-A-containing) and SAGA (Spt-Ada-Gcn5 acetyltransferase), containing histone acetyltransferase (HAT) activity, target genomic loci to increase promoter accessibility. To better understand the function of ATAC and SAGA HAT complexes, we used in vitro biochemical and biophysical assays to characterize human ATAC and SAGA HAT module interactions with nucleosomes and how a transcription factor (TF) coordinates these interactions. We found that ATAC and SAGA HAT modules bind nucleosomes with high affinity, independent of their HAT activity and the tested TF. ATAC and SAGA HAT modules directly interact with the VP16 activator domain and this domain enhances acetylation activity of both HAT modules. Surprisingly, ATAC and SAGA HAT modules increase TF binding to its DNA target site within the nucleosome by an order of magnitude independent of histone acetylation. Altogether, our results reveal synergistic coordination between HAT modules and a TF, where ATAC and SAGA HAT modules (i) acetylate histones to open chromatin and (ii) facilitate TF targeting within nucleosomes independently of their acetylation activity.
Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery
Authors: Buniello Annalisa , Suveges Daniel , Cruz-Castillo Carlos , Llinares Manuel Bernal , Cornu Helena , Lopez Irene , Tsukanov Kirill , Roldán-Romero Juan María , Mehta Chintan , Fumis Luca , McNeill Graham , Hayhurst James D , Martinez Osorio Ricardo Esteban , Barkhordari Ehsan , Ferrer Javier , Carmona Miguel , Uniyal Prashant , Falaguera Maria J , Rusina Polina , Smit Ines , Schwartzentruber Jeremy , Alegbe Tobi , Ho Vivien W , Considine Daniel , Ge Xiangyu , Szyszkowski Szymon , Tsepilov Yakov , Ghoussaini Maya , Dunham Ian , Hulcoop David G , McDonagh Ellen M , Ochoa David
Published: December 2024

The Open Targets Platform (https://platform.opentargets.org) is a unique, open-source, publicly-available knowledge base providing data and tooling for systematic drug target identification, annotation, and prioritisation. Since our last report, we have expanded the scope of the Platform through a number of significant enhancements and data updates, with the aim to enable our users to formulate more flexible and impactful therapeutic hypotheses. In this context, we have completely revamped our target–disease associations page with more interactive facets and built-in functionalities to empower users with additional control over their experience using the Platform, and added a new Target Prioritisation view. This enables users to prioritise targets based upon clinical precedence, tractability, doability and safety attributes. We have also implemented a direction of effect assessment for eight sources of target–disease association evidence, showing the effect of genetic variation on the function of a target is associated with risk or protection for a trait to inform on potential mechanisms of modulation suitable for disease treatment. These enhancements and the introduction of new back and front-end technologies to support them have increased the impact and usability of our resource within the drug discovery community.
Dicle University Hospital’s hospital disaster plan and emergency service management: Kahramanmaraş earthquake experience
Authors: Yaman Mahmut , Ülgüt Şilan Göger , Şen Abdullah , Ülgüt Ali Fırat , Belek Sema , Durgun Hasan Mansur
Published: December 2024

Background

Hospitals, being establishments with varying functions and capacities, must have disaster plans that reduce vulnerability, ensure the continuity, and possibly increase the capacity of healthcare services; these measures are crucial for reducing mortality and facilitating the normalization of life after a disaster. In this study, the aim was to analyze the operational process of the disaster management plan at Dicle University Faculty of Medicine Hospital following the earthquake in Kahramanmaraş on 6 February 2023.

Methods

This is a retrospective observational study. The study focused on determining the role of the hospital’s disaster plan in crisis situations, specifically examining the emergency service task distribution and management.

Results

The study included patients aged 1 to 85 years (median 34, mean 36.9 ± 19.0), with 52.5% being female. The median injury severity score was 17 (mean 20.1 ± 19.2). Hospital admission was 65.7%, with nephrology and orthopedics being the most common departments. Higher injury severity scores were significantly associated with mortality (P < .05), and dialysis and surgery rates were significantly higher in deceased patients (P < .05). No significant differences were found in age, gender, or comorbidities between groups.

Conclusion

The earthquake highlighted the importance of disaster preparedness in hospitals for effective patient care, collaboration among disciplines, and resource management. Detailed data on the hospital’s disaster plan and its operational process during the earthquake were provided to underscore its critical role in managing the crisis. Lessons learned will shape future disaster response protocols, stressing continual evaluation and improvement in healthcare disaster readiness.
O013 Sleep and overnight emotional memory in older adults with depression: A high-density EEG investigation
Authors: Riccardiello A , Wassing R , Kao C , Kumfor F , Ireland C , Bartlett D , Blackwell C , Grunstein R , McKinnon A , Naismith S , D’Rozario A
Published: December 2024

Older adults with depression have a high incidence of sleep disturbance which is posited to be mechanistically involved in maladaptive overnight emotional memory consolidation. In older adults (≥ 50 years) with and without depression, we aimed to compare group differences in overnight emotional memory and rapid eye movement (REM) and non-rapid eye movement (NREM) (N2 and N3) sleep disturbance. Secondly, we investigated the relationship between emotional memory consolidation, self-report emotional valence and arousal perception, and sleep disturbance.

Participants underwent overnight PSG with high-density EEG. An emotional memory image task with concurrent subjective emotional arousal and valence rating was completed before and after sleep. REM sleep disturbance was measured by REM sleep duration, global REM gamma and alpha activity and REM EEG arousal index. NREM sleep disturbance was measured by NREM sleep duration, global NREM delta, alpha and sigma power, and NREM EEG arousal index. T-tests and non-parametric tests were used for group comparisons. Linear regressions were used to assess relationships between sleep disturbance and emotional memory.

Twenty-two older adults (Depression: n = 12, Control: n = 10) with a mean age of 63.7 ± 6.5 years completed the study. Older adults with depression demonstrated differences in overnight perception of emotional valence and arousal for negative information, suggesting sleep may be involved in emotion perception. Global delta power in NREM was reduced in older adults with depression, suggestive of homeostatic alterations. However, no robust associations between overnight memory consolidation, emotional valence or arousal and REM or NREM sleep disturbance were observed.
O024 Bidirectional associations between maternal and infant sleep and mental health across the perinatal period
Authors: Astbury L , Crowther M , Pinnington D , Milgrom J , Bei B
Published: December 2024

Introduction

The bidirectional relationship between sleep and mental health in the perinatal periods is still poorly understood, with infant sleep rarely considered in this relationship. This longitudinal study investigated the bidirectional relationships between maternal sleep, infant sleep, and maternal depressive and anxiety symptoms over five years.

Methods

This is a secondary data analysis of a randomised controlled trial on maternal sleep health. A community sample of nulliparous participants (N=163, Mage=33.47, SDage=3.52) self-reported depressive and anxiety symptoms, maternal sleep, and infant sleep collected via questionnaires at 30- and 35 weeks’ gestation, 1.5, 3, 6, 12 and 24 months postpartum. Data were analysed using cross-lagged panel analyses, controlling for intervention condition in the larger randomised controlled trial.

Results

Variables were generally associated with each other at the same timepoint and the same variable tended to predict itself at the prospective timepoint. Depressive symptoms at 30 weeks’ gestation predicted maternal insomnia symptoms at 35 weeks’ gestation. Infant night-time sleep duration at 1.5m predicted maternal anxiety at 3m postpartum. Maternal insomnia scores at 1.5m, 6m and 12m predicted maternal anxiety at 3m, 12m, and 24m respectively. Depression symptoms at 12m postpartum predicted maternal insomnia symptoms at 24m postpartum.

Discussion

There are bidirectional associations between maternal, infant sleep and maternal mental health, and the direction of these associations differed between perinatal stages. Future studies are needed to better understand these relationships and examine whether intervening on sleep or mental health may be protective of the other.
O046 Autonomic Control of Heart Rate in Growth Hormone Naïve Children with Prader-Willi Syndrome
Authors: Patoglu O , Walter L , Davey M , Nixon G , Edwards B , Horne R
Published: December 2024

Background

Adults with Prader Willi syndrome (PWS) have an increased risk of cardiovascular morbidity and mortality, which may be due to impaired autonomic control. Heart rate variability (HRV) has been used in different populations as a strong and independent predictor of cardiac mortality and diseases. Studies have not assessed cardiovascular control in children with PWS during sleep while accounting for sleep disordered breathing severity which affects HRV.

Methods

Overnight electrocardiogram recordings during routine sleep studies in children with PWS pre-growth hormone treatment (n=48) and typically developing (TD) children matched in age, obstructive and central apnoea hypopnoea index, body mass index and sex were collected. Power spectral analysis determined HRV for total, low frequency (LF, sympathetic and parasympathetic activity), high frequency (HF, parasympathetic activity) power and LF/HF (sympathovagal balance) during N2, N3, REM and total sleep. Linear mixed-effects modelling adjusting for age, and obstructive and central sleep apnoea severity compared HRV parameters between children with PWS and TD children.

Results

Children with PWS had significantly reduced LF power in N2, REM and total sleep when compared to TD children (p<0.05 for all).

Conclusions

The significant reduction in LF power indicates children with PWS have reduced parasympathetic and sympathetic activity, which may increase cardiovascular risk, however longitudinal studies following children into adulthood are required to confirm this.
The role of silent mutations in KRAS-mutant tumors
Authors: Lu Jun , Zhou Chao , Pan Feng , Liu Hongyu , Jiang Haohua , Zhong Hua , Han Baohui
Published: December 2024

Silent mutations within the RAS gene have garnered increasing attention for their potential roles in tumorigenesis and therapeutic strategies. Kirsten-RAS (KRAS) mutations, predominantly oncogenic, are pivotal drivers in various cancers. While extensive research has elucidated the molecular mechanisms and biological consequences of active KRAS mutations, the functional significance of silent mutations remains relatively understudied. This review synthesizes current knowledge on KRAS silent mutations, highlighting their impact on cancer development. Silent mutations, which do not alter protein sequences but can affect RNA stability and translational efficiency, pose intriguing questions regarding their contribution to tumor biology. Understanding these mutations is crucial for comprehensively unraveling KRAS-driven oncogenesis and exploring novel therapeutic avenues. Moreover, investigations into the clinical implications of silent mutations in KRAS-mutant tumors suggest potential diagnostic and therapeutic strategies. Despite being in early stages, research on KRAS silent mutations holds promise for uncovering novel insights that could inform personalized cancer treatments. In conclusion, this review underscores the evolving landscape of KRAS silent mutations, advocating for further exploration to bridge fundamental biology with clinical applications in oncology.
Chalazia: A Scoping Review to Identify the Evidence Behind Treatments
Authors: Park James K. , Vyas Charu , Dagi Glass Lora R.
Published: December 2024

Purpose:

Current treatment approaches aimed at resolving a chalazion vary greatly among practice settings and practitioners. Our objective is to provide a review of existing literature on treatment modalities aimed at resolving a chalazion.

Methods:

We conducted a review of existing peer-reviewed publications that described treatment methods aimed at resolving chalazia in patients of any age. Literature searches were conducted using PubMed, Embase, and Cochrane. A 3-stage review process was conducted by 2 trained reviewers, including an initial screening, a full-text review, and data extraction. Articles were assessed for baseline study identifiers, study design, country of origin, number of patients, demographic characteristics, types and number of treatments administered, and resolution rates. Publications were graded using the Oxford Centre for Evidence-Based Medicine levels of evidence table.

Results:

A total of 2814 articles were initially identified based on database queries; 39 studies met inclusion criteria for full-text review. The most represented study design was case series (15), followed by randomized controlled trials (14). Twenty-five publications discussed intralesional corticosteroid injections, 18 discussed incision or excision and curettage, 5 discussed conservative treatments, and 8 discussed topical antibiotic±steroid treatments. Both the definition of chalazion resolution and resolution rates for each treatment modality varied widely between publications.

Conclusions:

Procedural management of chalazia, including corticosteroid injections and surgical management, is most often studied in the literature. Fewer publications exist on the efficacy of conservative and topical treatments.
Nursing Resilience
Authors: George Nicole , Warshawsky Nora E. , Doucette Jeffrey
Published: December 2024

Nurse resilience took a hard hit during the COVID-19 pandemic and is showing signs of stabilization. Nationally, nurse leaders ask for guidance to better support frontline nurses. We conducted a review of literature to identify interventions to improve nurse resilience. This article presents a review and critique of individual-, team-, and system-level interventions to support frontline nurses. Nurse leaders are encouraged to implement systematic strategies to help frontline nurses disconnect from work.
Differences in Nurse Practitioner Work Effectiveness by Level of Education and Work Experience
Authors: Hampton Debra , Melander Sheila , Rayens Mary Kay
Published: December 2024

OBJECTIVE

The purpose of this study was to assess the association of educational level, work experience, and other demographic factors with the perceived impact of nurse practitioner role effectiveness.

BACKGROUND

Nurse practitioners (NPs) bring value by impacting patient and organizational outcomes in multiple ways. Employers report difficulties differentiating between how MSN- versus DNP-educated NPs affect patient and organizational outcomes.

METHODS

A cross-sectional descriptive survey design was used in this study that included demographic variables, productivity information, and variables related to perceived organizational outcome impacts.

RESULTS

Participants included 128 NPs with an average of 9.5 years of experience as an NP. Years of practice as an NP was correlated with age. Educational preparation (MSN or DNP) was significantly correlated with overall perceived organizational outcomes and with specific outcomes.

CONCLUSIONS

Based on the results of this study, hiring DNP-prepared NPs is expected to bring a return-on-investment value for organizations.
Assessing alexithymia in chronic pain: psychometric properties of the Toronto Alexithymia Scale-20 and Perth Alexithymia Questionnaire
Authors: Aaron Rachel V. , Preece David A. , Heathcote Lauren C. , Wegener Stephen T. , Campbell Claudia M. , Mun Chung Jung
Published: December 2024

Introduction:

Alexithymia is elevated in chronic pain and relates to poor pain-related outcomes. However, despite concerns from other clinical populations, the psychometric properties of alexithymia measures have not been rigorously established in chronic pain.

Objective:

This study examined the psychometric properties of the Toronto Alexithymia Scale-20 Item (TAS-20) and the Perth Alexithymia Questionnaire (PAQ) in adults with chronic pain.

Methods:

An online sample of adults with chronic pain across the United States (N = 1453) completed the TAS-20, PAQ, and related questionnaires at baseline, 3-month follow-up, and 12-month follow-up.

Results:

Both measures showed good temporal stability, convergent validity (with emotion regulation scores), divergent validity (with depression and anxiety scores), and criterion validity. Some concerns were raised about the TAS-20: the original 3-factor structure showed a poor model fit; the Externally Oriented Thinking subscale of the TAS-20 had poor factor loadings and unacceptable internal consistency; and, we identified several TAS-20 items that may slightly inflate the predictive validity of the TAS-20 on pain-related outcomes. The original 5-factor structure of the PAQ showed a good fit; each PAQ subscale had good factor loadings and excellent internal consistency.

Conclusions:

Both the TAS-20 and PAQ had psychometric strengths. Our data raised some concern for the use of TAS-20 subscales; the PAQ may be a psychometrically stronger option, particularly for investigators interested in alexithymia subscale analysis in people with chronic pain.
Dopamine dynamics in chronic pain: music-induced, sex-dependent, behavioral effects in mice
Authors: Flores-García Montse , Flores África , Aso Ester , Otero-López Paloma , Ciruela Francisco , Videla Sebastià , Grau-Sánchez Jennifer , Rodríguez-Fornells Antoni , Bonaventura Jordi , Fernández-Dueñas Víctor
Published: December 2024

Introduction:

Chronic pain is a debilitating disease that is usually comorbid to anxiety and depression. Current treatment approaches mainly rely on analgesics but often neglect emotional aspects. Nonpharmacological interventions, such as listening to music, have been incorporated into clinics to provide a more comprehensive management of chronic pain. However, the underlying mechanisms of music-mediated pain relief are not fully understood.

Objectives:

Our aim was to evaluate the effects and mechanisms of music exposure in an animal model of chronic pain.

Methods:

We injected mice with the complete Freund adjuvant (CFA) inflammatory agent into the hind paw and housed them for 14 days with background music, or ambient noise, during their active period (Mozart K.205, overnight). The effect of music exposure on nociception, anxiety-like behaviors, and depression-like behaviors was evaluated through different paradigms, including the hot plate, Von Frey, elevated plus maze, splash, and tail suspension tests. In addition, we conducted fiber photometry experiments to investigate whether music influences dopamine dynamics in the nucleus accumbens (NAcc), a crucial region involved in pain processing, anhedonia, and reward.

Results:

Our findings indicate that music exposure prevents the decrease in NAcc activity observed in CFA-injected mice, linking with a sex-dependent reduction in allodynia, anxiety-like behaviors, and depression-like behaviors. Accordingly, female mice were more sensitive to music exposure than male mice.

Conclusion:

Collectively, our findings provide compelling evidence for the integration of music as a nonpharmacological intervention in chronic pain conditions. Moreover, the observed effect on NAcc suggests its potential as a therapeutic target for addressing chronic pain and its associated symptoms.
Insights into Dentatorubral-Pallidoluysian Atrophy from a newDrosophilamodel of disease
Authors: Prifti Matthew V. , Nuga Oluwademilade , Dulay Ryan O. , Patel Nikhil C. , Kula Truman , Libohova Kozeta , Jackson-Butler Autumn , Tsou Wei-Ling , Richardson Kristin , Todi Sokol V.
Published: December 2024

Dentatorubral-pallidoluysian atrophy (DRPLA) is a neurodegenerative disorder that presents with ataxia, dementia and epilepsy. As a member of the polyglutamine family of diseases, DRPLA is caused by abnormal CAG triplet expansion beyond 48 repeats in the protein-coding region ofATROPHIN 1(ATN1), a transcriptional co-repressor. To better understand DRPLA, we generated newDrosophilalines that express full-length, human ATN1 with a normal (Q7) or pathogenic (Q88) repeat. Expression of ATN1 is toxic, with the polyglutamine-expanded version being consistently more problematic than wild-type ATN1. Fly motility, longevity and internal structures are negatively impacted by pathogenic ATN1. RNA-seq identified altered protein quality control and immune pathways in the presence of pathogenic ATN1. Based on these data, we conducted genetic experiments that confirmed the role of protein quality control components that ameliorate or exacerbate ATN1 toxicity. Hsc70-3, a chaperone, arose as a likely suppressor of toxicity. VCP (a proteasome-related AAA ATPase), Rpn11 (a proteasome-related deubiquitinase) and select DnaJ proteins (co-chaperones) were inconsistently protective, depending on the tissues where they were expressed. Lastly, informed by RNA-seq data that exercise-related genes may also be involved in this model of DRPLA, we conducted short-term exercise, which improved overall fly motility. This new model of DRPLA will prove important to understanding this understudied disease and will help to identify therapeutic targets for it.