bluuebunny/crossref_metadata_2025_split huggingface dataset:
(402) Peyronie's Disease Treatment- Active Vs. Stable Phase- Retrospective Review of Cases
Authors: Gal J , Marinaro J , Bhambhvani H , Lassiter S , Brant A , Kashanian J 
Published: February 2024

Abstract

Introduction
Peyronie's disease (PD) may be treated with collagenase clostridium histolyticum (CCH) during the stable phase. However, the effectiveness and safety of this treatment during the active phase remain unclear. To address this, we investigated and compared the outcomes of patients receiving treatment in the active phase versus the stable phase of PD.

Objective
To assess the effectiveness and safety of CCH treatment in patients diagnosed with PD during the active phase.

Methods
A retrospective review was conducted on men who underwent at least one cycle of CCH injections for PD with a single fellowship-trained urologist between 2017 and 2023. Active PD was defined as occurring within one year from the onset of symptoms. The severity of penile curvature was measured at the point of maximal curvature and assessed at baseline and after each CCH cycle. In addition to the CCH treatment, patients were prescribed daily phosphodiesterase inhibitors (PDEi) and coenzyme-Q10 (CoQ-10). The treatment response was defined as any improvement in curvature from baseline to the final assessment. The characteristics and outcomes of patients were compared between those with active and stable PD.

Results
Of 107 patients who underwent CCH treatment, 75 were diagnosed with stable PD and 32 with active PD. There were no significant differences observed between the two groups in terms of age (58.1 vs. 57.9 years, p = 0.89), baseline curvature (58.4 vs. 60.5 degrees, p = 0.60), or the number of CCH cycles received (6.6 vs. 6.3 cycles, p = 0.57). Among the active PD patients, 26 (81.2%) experienced an improvement in curvature, which was comparable to the stable PD group (58 (77.3%), p = 0.85). There were no significant differences in the degree of curvature improvement (14.4 vs. 14.0 degrees, p = 0.91) or the percentage of improvement from baseline (22.67% vs. 24.05%, p = 0.86) between the active and stable PD patients. In the subset of patients who showed an improvement in curvature angle, there was no notable distinction in the percentage of improvement from baseline between the stable and active phases (37.4% vs 34.8%, p=0.63). Among the treated patients, we observed two cases of potential penile fractures in the stable phase. All adverse events were conservatively managed.

Conclusions
Patients treated with CCH during the active phase achieved comparable outcomes to those in the stable phase. There were no additional adverse events in the active phase treatment group. These data suggest that early active phase treatment yields similar effectiveness as treatment administered during the stable phase. Treatment during the active phase could be a disease modifier and may change the course of progression.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Endo, Roman Health.
(403) Pilot Study: Fractional CO2 Laser in the Treatment of Chronic Phase Peyronie’s Disease
Authors: Chan J , Alhamam A , Witherspoon L , Rivers J , Flannigan R 
Published: February 2024

Abstract

Introduction
Peyronie’s Disease (PD) is a fibrosing disorder of the penis which may result in penile curvature and deformity of the erect penis. Fractional CO2 laser therapy has been used to remodel severe skin scarring and more recently led to improvements in Dupytren’s contractures.

Objective
We sought to evaluate the safety of Fractional CO2 Laser Therapy in treating Peyronie’s disease. The assessment includes changes in penile curvature, Peyronie’s Disease Questionnaire (PDQ) Symptom bother score, and International Index of Erectile Function (IIEF) scores.

Methods
This pilot study examined the use of fractional CO2 laser therapy with adjuvant topical triamcinolone (10mg/cc) in patients with PD. Each patient underwent three treatment cycles with 6 weeks interval between each treatment. During the interval time period, patients were required to perform at-home penile modeling three times daily. Penile curvature assessments, self-reported questionnaires and any adverse events were collected at baseline, 24 weeks and 52 weeks.

Results
A total of 5 patients were included. The mean baseline curvature was 41.80 ± 10.57 degrees and at 24-week follow-up mean curvature was found to be 34.20 ±18.21 degrees, resulting in an 18.1% reduction in curve (p=0.44). Mean IIEF scores were 55.40 ± 14.26 vs. 61.40 ± 6.58, (p=0.234) at baseline and 24-week follow-up, respectively. Similarly, the IIEF erectile function domain scores were 24.40 ± 4.72 vs. 28.60 ±1.52, (p=0.061) at baseline and 24-week, respectively. PDQ symptom bother average scores were 7.6 vs. 5.4 at baseline and 24-week, respectively. Mild adverse effects such as temporary bruising and penile pain were reported. There were no significant adverse events noted.

Conclusions
Preliminary results, at 24 weeks, suggest that fractionated CO2 laser therapy may serve as a well-tolerated therapy for PD. While this pilot trial was not powered to assess effectiveness, initial results are encouraging. Based upon these findings, a dose escalating phase I clinical trial is warranted to further systematically evaluate the tolerability and utility of Fractional CO2 laser therapy in the treatment of PD.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Boston Scientific. Allergen/Abvie, Galderma, Johnson and Johnson, Leo, MetOptima, Pfizer.
On the role of minor neutrals in determining the characteristic features of the Venus ionosphere at low altitudes
Authors: Ambili K M , Choudhary R K , Tripathi K R 
Published: February 2024

ABSTRACT
Electron density profiles obtained from radio occultation experiments reveal significant ionization occurring at altitudes below 120 km in the Venusian ionosphere. The presence of such ionization remains unexplained when considering only major neutrals and the resulting ion chemistry. In this study, we investigate the role of minor neutrals, including NO, O2, C, Ar, H2, and H, in the lower altitudes of the Venusian ionosphere using a one-dimensional photochemical model and Akatsuki radio science measurements. We derive the density of minor neutrals from the profiles of major neutrals. Our analysis demonstrates that NO+ and O$_2^+$ ions exhibit a notable presence below 140 km. When we incorporate the minor neutrals, electron density increases below 115 km but remains unchanged above this altitude. Specifically, the density of NO+ increases below 125 km, with corresponding reductions in O$_2^+$. The increase in NO+ above 115 km can be attributed to the charge-exchange reaction between O$_2^+$ and NO. However, below 115 km, the photoionization of NO results in a net increase in NO+ and electron density. These findings highlight the significant role played by minor neutrals, particularly below 115 km, in shaping the Venusian ionosphere at low altitudes.
Examining baryonic Faber–Jackson relation in galaxy groups
Authors: Sadhu Pradyumna , Tian Yong 
Published: February 2024

ABSTRACT
We investigate the baryonic Faber–Jackson relation (BFJR), examining the correlation between baryonic mass and velocity dispersion in galaxy groups and clusters. Originally analysed in elliptical galaxies, the BFJR is derivable from the empirical radial acceleration relation (RAR) and MOdified Newtonian Dynamics (MOND), both showcasing a characteristic acceleration scale $\mathrm{g}_\mathrm{\dagger }=1.2\times 10^{-10}\, \mathrm{m}\, \mathrm{s}^{-2}$. Recent interpretations within MOND suggest that galaxy group dynamics can be explained solely by baryonic mass, hinting at a BFJR with g† in these systems. To explore this BFJR, we combined X-ray and optical measurements for 6 galaxy clusters and 13 groups, calculating baryonic masses by combining X-ray gas and stellar mass estimates. Simultaneously, we computed spatially resolved velocity dispersion profiles from membership data using the biweight scale in radial bins. Our results indicate that the BFJR in galaxy groups, using total velocity dispersion, aligns with MOND predictions. Conversely, galaxy clusters exhibit a parallel BFJR with a larger acceleration scale. Analysis using tail velocity dispersion in galaxy groups shows a leftward deviation from the BFJR. Additionally, stacked velocity dispersion profiles reveal two distinct types: declining and flat, based on two parallel BFJRs. The declining profile, if not due to the anisotropy parameters or the incomplete membership, suggests a deviation from standard dark matter (DM) density profiles. We further identify three galaxy groups with unusually low DM fractions.
ProPane: image warping with fire
Authors: Robotham A S G , Tobar R , Bellstedt S , Casura S , Cook R H W , D’Silva J C J , Davies L J , Driver S P , Li J , Garate-Nuñez L P 
Published: February 2024

ABSTRACT
In this paper, we introduce the software package propane, written for the r data analysis language. propane combines the full range of wcslib projections with the C++ image manipulation routines provided by the cimg library. propane offers routines for image warping and combining (including stacking), and various related tasks such as image alignment tweaking and pixel masking. It can stack an effectively unlimited number of target frames using multiple parallel cores, and offers threading for many lower level routines. It has been used for a number of current and upcoming large surveys, and we present a range of its capabilities and features. propane is already available under a permissive open-source LGPL-3 license at github.com/asgr/ProPane (DOI: 10.5281/zenodo.10057053).
Dynamics of baryon ejection in magnetar giant flares: implications for radio afterglows, r-process nucleosynthesis, and fast radio bursts
Authors: Cehula Jakub , Thompson Todd A , Metzger Brian D 
Published: February 2024

ABSTRACT
We explore the impact of a magnetar giant flare (GF) on the neutron star (NS) crust, and the associated baryon mass ejection. We consider that sudden magnetic energy dissipation creates a thin high-pressure shell above a portion of the NS surface, which drives a relativistic shockwave into the crust, heating a fraction of these layers sufficiently to become unbound along directions unconfined by the magnetic field. We explore this process using spherically symmetric relativistic hydrodynamical simulations. For an initial shell pressure PGF we find the total unbound ejecta mass roughly obeys the relation $M_{\rm {ej}}\sim 4\!-\!9\times 10^{24}\, \rm {g}\, (P_{\rm GF}/10^{30}\, \rm {erg}\, \rm {cm}^{-3})^{1.43}$. For $P_{\rm {GF}}\sim 10^{30}\!-\!10^{31}\, \rm {erg}\, \rm {cm}^{-3}$ corresponding to the dissipation of a magnetic field of strength $\sim 10^{15.5}\!-\!10^{16}\, \rm {G}$, we find $M_{\rm {ej}}\sim 10^{25}\!-\!10^{26}\, \rm {g}$ with asymptotic velocities vej/c ∼ 0.3–0.6 compatible with the ejecta properties inferred from the afterglow of the 2004 December GF from SGR 1806-20. Because the flare excavates crustal material to a depth characterized by an electron fraction Ye ≈ 0.40–0.46, and is ejected with high entropy and rapid expansion time-scale, the conditions are met for heavy element r-process nucleosynthesis via the alpha-rich freeze-out mechanism. Given an energetic GF rate of roughly once per century in the Milky Way, we find that magnetar GFs could be an appreciable heavy r-process source that tracks star formation. We predict that GFs are accompanied by short ∼minutes long, luminous $\sim 10^{39}\, \rm {erg}\, \rm {s}^{-1}$ optical transients powered by r-process decay (nova brevis), akin to scaled-down kilonovae. Our findings also have implications for the synchrotron nebulae surrounding some repeating fast radio burst sources.
Carrageenan oligosaccharide alleviates intestinal damage via gut microflora through activating IMD/relish pathway in female Drosophila melanogaster
Authors: Wang Lu , Zhang Guocai , Li Qiaowei , Lu Fangyuan , Yang Kun , Dai Xianjun 
Published: February 2024

AbstractRecent evidence suggests the anti‐inflammatory effect of carrageenan oligosaccharides (COS). The effects of COS on intestinal injury induced by 0.6% sodium dodecyl sulfate (SDS) and the molecular mechanisms involved were investigated in this study. 0.625, 1.25, and 2.5 mg/mL COS in diet had no toxic effect in flies, and they could all prolong SDS‐treated female flies' survival rate. 1.25 mg/mL COS prevented the development of inflammation by improving the intestinal barrier integrity and maintaining the intestinal morphology stability, inhibited the proliferation of intestine stem cells (ISCs), and the production of lysosomes induced by SDS, accompanied by a decrease in the expression of autophagy‐related genes. Moreover, COS decreased the active oxygen species (ROS) content in gut and increased the antioxidant activity in SDS‐induced female flies, while COS still played a role in increasing survival rate and decreasing intestinal leakage in CncC‐RNAi flies. The improvement of anti‐inflammation capacity may be associated with the regulation of intestinal microflora with COS supplementation for Drosophila melanogaster. COS changed the gut microbiota composition, and COS had no effect on germ‐free (GF) flies. It is highlighted that COS could not work in Relish‐RNAi flies, indicating relish is required for COS to perform beneficial effects. These results provide insights into the study of gut microbiota interacting with COS to modulate intestinal inflammation in specific hosts.
Digital PCR-based deep quantitative profiling delineates heterogeneity and evolution of uveal melanoma
Authors: Nell R.J. , Versluis M. , Menger N.V. , Verdijk R.M. , Kroes W.G.M. , Kapiteijn H.W. , Luyten G.P.M. , Jager M.J. , van der Velden P.A. 
Published: February 2024

AbstractUveal melanoma is an aggressive intraocular tumour characterised by a limited number of genetic alterations. However, the evolution of this malignancy remains enigmatic. In this study, we performed a deep quantitative analysis of 80 primary uveal melanomas by novel digital PCR-based approaches. Mutations were quantified by targeted and drop-off mutation assays, copy number alterations were precisely measured by quantifying the allelic imbalance of heterozygous single-nucleotide polymorphisms. By comparing the absolute abundances of genetic alterations present in a bulk tumour, the heterogeneity and early evolution could be inferred. Tumour progression was further studied by analysing matched primary and metastatic lesions from five patients.Gαqsignalling mutations were generically and always clonally present, suggesting to be acquired in the earliest stage of uveal melanoma development (‘primary driver’). Next, three main evolutionary subtypes could be identified based on having anEIF1AXmutation,SF3B1mutation or monosomy 3p. These alterations were usually mutually-exclusive and (near-) clonally abundant, suggesting to represent distinct secondary drivers. This contrasts with gains and amplifications of chromosome 8q, which were not restricted to one of the main subtypes and showed subclonality in 31% of the affected tumours. These tertiary alterations were not required for metastatic dissemination.Using high-resolution analyses, we identified systematic differences in the evolutionary timing of genetic events in uveal melanoma. The observed intratumour heterogeneity suggests a more complex model of gradual tumour evolution and argues for a comprehensive genetic analysis in clinical practice, which may be facilitated by the sensitive digital PCR assays developed in this study.
Cardiorespiratory Dynamics During Prone Positioning for Severe Ards: A Retrospective Cohort Study
Authors: Barros Andrew , Lee Seung Wook , Moorman J. Randall 
Published: February 2024

ABSTRACTObjectivesTo elucidate the changes in cardiorespiratory dynamics during neuromuscular blockade and prone positioning and determine the associations between changes in cardiorespiratory dynamics following prone positioning and mortality.DesignSingle center retrospective cohort study of patients admitted to the medical ICU between June 1, 2020 and September 1, 2022 who received prone positioning while mechanically ventilated.ResultsOur final cohort consisted of 136 patients. Prone position was associated with an improvement in A-a gradient of 113 mmHg (95% CrI 78 – 149) between the pre-proning values and 10 hours post proning. Norepinephrine dose did not significantly change before and after prone positioning (Estimated difference: 0.04 mcg/min 95% CrI -1.00 – 1.07). For the outcome of 7-d mortality, there was a high probability that the baseline factors of increasing age, male sex, and higher baseline A-a gradient were associated with increased risk of death. Increased total vasopressor requirement and increased in PCO2 were associated with worse prognosis while a decrease in instantaneous heart rate and a decrease in heart rate variability were associated with improved prognosis.ConclusionThe immediate changes in prone positioning primarily impact respiratory physiology, with limited influence on circulatory parameters. Predictors of short-term mortality after prone positioning include both respiratory and cardiovascular parameters suggesting that extrapulmonary effects, such as improvement in right ventricular heart function, might also contribute to the benefit of prone positioning.
AI-Driven Predictive Biomarker Discovery with Contrastive Learning to Improve Clinical Trial Outcomes
Authors: Arango-Argoty Gustavo , Bikiel Damian E. , Sun Gerald J. , Kipkogei Elly , Smith Kaitlin M. , Pro Sebastian Carrasco , Jacob Etai 
Published: February 2024

ABSTRACTModern clinical trials can capture tens of thousands of clinicogenomic measurements per individual. Discovering predictive biomarkers, as opposed to prognostic markers, is challenging when using manual approaches. To address this, we present an automated neural network framework based on contrastive learning—a machine learning approach that involves training a model to distinguish between similar and dissimilar inputs. We have named this framework the Predictive Biomarker Modeling Framework (PBMF). This general-purpose framework explores potential predictive biomarkers in a systematic and unbiased manner, as demonstrated in simulated “ground truth” synthetic scenarios resembling clinical trials, well-established clinical datasets for survival analysis, real-world data, and clinical trials for bladder, kidney, and lung cancer. Applied retrospectively to real clinicogenomic data sets, particularly for the complex task of discovering predictive biomarkers in immunooncology (IO), our algorithm successfully found biomarkers that identify IO-treated individuals who survive longer than those treated with other therapies. In a retrospective analysis, we demonstrated how our framework could have contributed to a phase 3 clinical trial (NCT02008227) by uncovering a predictive biomarker based solely on early study data. Patients identified with this predictive biomarker had a 15% improvement in survival risk, as compared to those of the original trial. This improvement was achieved with a simple, interpretable decision tree generated via PBMF knowledge distillation. Our framework additionally identified potential predictive biomarkers for two other phase 3 clinical trials (NCT01668784,NCT02302807) by utilizing single-arm studies with synthetic control arms and identified predictive biomarkers with at least 10% improvement in survival risk. The PBMF offers a broad, rapid, and robust approach to inform biomarker strategy, providing actionable outcomes for clinical decision-making.
The heartbeat-evoked potential in young and older adults during attention orienting
Authors: Aprile Francesca , Simões Marco , Henriques Jorge , Carvalho Paulo , Castelo-Branco Miguel , Sel Alejandra , Ribeiro Maria J. 
Published: February 2024

AbstractCardiac cycle duration, or interbeat interval (IBI), is the period from one heartbeat to the next. IBI changes from cycle to cycle. Periods with longer IBI are associated with higher sensitivity to external sensory stimuli (exteroception). Warning cues induce a state of attentive anticipation characterized by an increase in IBI (anticipatory cardiac deceleration) and faster reaction times. Ageing reduces the increase in IBI induced by warning cues and response speed. However, it is unclear which mechanism, if any, connects IBI with reaction time. The heartbeat-evoked potential (HEP) is a cortical response evoked by the heartbeat, modulated by attention and associated with sensitivity to external sensory stimuli. HEP might be affected by IBI and mediate the association between cardiac output and cortical processing.We investigated if the HEP was affected by warning cues as well as spontaneous fluctuations in IBI. To explore the impact of age-related changes in cardiac responses, we included young and older people [N = 33/29; 26/23 women; mean age 23/61 years]. We analysed the electroencephalograms and electrocardiograms simultaneously acquired during auditory cued simple reaction time and go/no-go tasks.The warning cue did not induce significant changes in the HEP. Yet, fluctuations in IBI (not locked with the warning cue) affected the HEP and HEP amplitude was associated with average reaction time in the older group. However, on a trial-by-trial basis, reaction time was independent from IBI fluctuations.In conclusion, we found no evidence that the HEP mediates the effect of attention orienting on reaction time.
Genetic interference with HvNotch provides new insights into the role of the Notch-signalling pathway for developmental pattern formation inHydra
Authors: Pan Qin , Mercker Moritz , Klimovich Alexander , Wittlieb Jörg , Marciniak-Czochra Anna , Böttger Angelika 
Published: February 2024

AbstractThe Notch-signalling pathway plays an important role in pattern formation inHydra. Using pharmacological Notch inhibitors (DAPT and SAHM1), it has been demonstrated that HvNotch is required for head regeneration and tentacle patterning inHydra. HvNotch is also involved in establishing the parent-bud boundary and instructing buds to develop feet and detach from the parent. To further investigate the functions of HvNotch, we successfully constructed NICD (HvNotch intracellular domain)-overexpressing and HvNotch-knockdown transgenicHydrastrains. NICD-overexpressing transgenicHydrashowed a pronounced inhibition on the expression of predicted HvNotch-target genes, suggesting a dominant negative effect of ectopic NICD. This resulted in a “Y-shaped” phenotype, which arises from the parent-bud boundary defect seen in polyps treated with DAPT. Additionally, “multiple heads”, “two-headed” and “ectopic tentacles” phenotypes were observed. The HvNotch-knockdown transgenicHydrawith reduced expression of HvNotch exhibited similar, but not identical phenotypes, with the addition of a “two feet” phenotype. Furthermore, approximately 20% of the HvNotch-knockdown polyps were unable to regenerate a new head after decapitation. We integrated these findings into a mathematical model based on long-range gradients of signalling molecules underlying sharply defined positions of HvNotch-signalling cells at theHydratentacle and bud boundaries.