bluuebunny/crossref_metadata_2025 huggingface dataset:
PD223 Early Dialogue With Researchers: The Case Of The OPTIBIO Study, Innovating From The Investigation Stages
Authors: Paz-Valiñas Lucinda , Rotea-Salvo Sandra , Carmen Maceira-Rozas Maria del , Casal-Acción Beatriz , Vallés María-José Faraldo
Published: January 2025

Introduction

An early dialogue (ED) is non-binding scientific advice given to industry in the initial stages of technology development to help create evidence that the health technology assessment (HTA) agency will request. ED could also be used in the academic ecosystem. We report our experience with the clinical validation of an algorithm to predict persistent remission in patients with rheumatoid arthritis treated with biological therapy.

Methods

A systematic review (SR) was undertaken to compare optimization algorithms with current clinical management. The review focused on the effectiveness and safety of these tools and included clinical practice guidelines, SRs, and primary studies. Several meetings took place between the research team and HTA researchers to integrate HTA requirements (e.g., choice of comparators, relevant outcomes, quality of life, and patient groups) into the study design to ensure the quality and accuracy assurance of data collected as well as the proper monitoring of good clinical practice.

Results

Local clinical practice guidelines pointed to the importance of optimization strategies to select the most suitable patients in remission. However, there is currently no validated algorithm to select these patients. The literature search retrieved 1,809 references. There were no primary studies identified and only two ongoing randomized controlled trials met the inclusion criteria: REMRABIT-Plus (OPTIBIO) and PATIO. There were some important differences between the studies with respect to the patient populations and stages of the disease. Based on these results, the review will continue in “living evidence” mode, with the aim of collecting new evidence as it becomes available.

Conclusions

There is currently an unfulfilled need between research projects in the academic context and HTA that can be resolved with ED. Collaboration in the early stages of technology development is fundamental to improving the appropriateness of data produced for future HTAs. This will facilitate quality decision-making on the incorporation of procedures into the National Health Service.
PD231 A New Way Of Identifying And Selecting Health Technology Assessment Topics: Using Social Media And Citizen Involvement
Authors: Jung Yeryeon , Lee Sou Hyun , Choi Hayoung
Published: January 2025

Introduction

As unfiltered health information overflows through social networking services, people’s health rights are being violated and unnecessary medical expenses are increasing. Citizens and patients participating in the group initiative Public Involvement in the National Evidence-based Healthcare Collaborating Agency (NECA), the sole health technology assessment (HTA) agency in South Korea, began monitoring information on health technology in social media from 2021 as a new way to identify HTA topics.

Methods

Citizens and patients in Public Involvement in NECA were provided with search keywords related to “common diseases on general public” and “diseases with high public interest”. They monitored social media platforms for one month and collected information about health technologies, such as medicines and treatments without scientific evidence on their safety and effectiveness. The target information included subjective information on health technologies based on personal experience; information with unclear sources; information that might cause excessive anxiety and fear; and information with a high risk of side effects. Information was collected from the internet and a checklist was given to the participants to evaluate the suitability of the information.

Results

In the topic selection process, NECA, and the Korean Society of Science Journalists (KSIA) evaluated the priority of HTA topics developed from the collected information. HTA topics were evaluated using five criteria, including the possible harm the information might cause throughout society. As a result, the safety and effectiveness of saw palmetto in patients with prostatic hyperplasia and high-dose intravenous vitamin C in patients with cancer were selected. NECA conducted health technology reassessments on these topics and was able to successfully disseminate the reassessment results in collaboration with the KSIA.

Conclusions

Participation in the HTA process using social media lowered the barriers that laypersons experience with HTA and increased the possibility of bringing HTA topics closer to citizens’ lives. However, as there were difficulties in collecting meaningful information for developing a HTA topic, providing systematic training on health information monitoring remains a challenge.
PD241 Supporting Patient Groups To Enhance Their Input To Health Technology Assessment
Authors: Cairns Daniel , Russell Kate , McCormack Jackie , Dickson Jennifer
Published: January 2025

Introduction

The Scottish Medicines Consortium (SMC) patient group submission process includes a written submission of patient experience evidence from Patient Group Partners (PGPs). To maximize the relevance and quality of information included in submissions, the first draft is reviewed by the Public Involvement Team and feedback is provided. The submission is then amended by the submitting PGP before final submission.

Methods

Upon receiving a new written patient group submission, the Public Involvement Team reviews it and provides feedback highlighting any evidence gaps and areas where wording could be amended to strengthen the patient voice. The draft submission is then amended by the submitting PGP, with support from the SMC reviewer. Once finalized, the submission is collated into the body of evidence used by the SMC Committee members to assess a new medicine. The satisfaction of participating PGPs is continually assessed by an online survey. During the 2021 to 2023 period, the SMC received 232 patient group submissions, with 77 percent being amended and strengthened after receiving feedback.

Results

The feedback and collaboration on amendments to draft submissions has improved the quality of patient experience evidence submitted to the SMC by PGPs. PGPs value their draft evidence being reviewed by the SMC Public Involvement Team prior to final submission. This approach resulted in high levels of trust in and satisfaction with how the SMC involves patient representatives in medicine assessments. In 2022, 89 percent of the 28 PGPs surveyed were very satisfied and 11 percent were satisfied with the support provided during the submission process.

Conclusions

Evaluation of the SMC’s formal process to provide input and feedback on draft written patient group submissions demonstrates high levels of satisfaction with how the SMC works in partnership with PGPs. This approach has strengthened written evidence of patient experiences for SMC assessments. Furthermore, it helps to build and maintain a partnership approach in how the SMC works with PGPs.
“A little world within itself”: The South Carolina Penitentiary and the Roots of the Carceral State
Authors: Butorac Sean Kim
Published: January 2025

This article tracks the buildup of the South Carolina criminal legal system between 1867 and 1899 through three eras of its state penitentiary: from the politics of reform to convict leasing to the prison plantation. To track the delayed emergence and unusual trajectory of South Carolina’s criminal legal system, I argue that two approaches became entangled after the Civil War: On the one hand, a modern, nationalized politics of reform, and on the other, a decidedly Southern vision of crime and punishment haunted by the afterlife of slavery. It was the tension between—and variegated blending of—these two approaches that yielded a hybrid carceral project and set the trajectory for the state’s criminal legal system as it entered the twentieth century.
Isolated pulmonary valve endocarditis leading to right ventricular outflow obstruction
Authors: Kulkarni Ankita , Sabnis Girish , Rathod Keyur Rajendra
Published: January 2025

Isolated native pulmonary valve endocarditis is rare. We present a rare case of isolated native pulmonary valve endocarditis resulting in severe right ventricular outflow tract obstruction in an immunocompetent patient with surgically repaired ventricular septal defect caused by Burkholderia cepacia.
Changes in grocery shopping behaviour among low-income households during the COVID-19 pandemic
Authors: Trude Angela CB , Lowery Caitlin M , Vedovato Gabriela M , Ali Shahmir H , Dudzik Josephine M
Published: January 2025

Objective:

The Supplemental Nutrition Assistance Program (SNAP) Online Purchasing Pilot (OPP) authorised the use of SNAP benefits online in Maryland in May 2020. We assessed shopping behaviour and intentions associated with uptake and intended future use of online grocery shopping during and after COVID-19 among SNAP-eligible households.

Design:

In this mixed-methods study, participants completed a survey on online grocery shopping, and a purposefully sampled subset participated in focus groups or in-depth interviews between November 2020 and March 2021.

Setting:

Predominantly urban households in Maryland

Participants:

Primary shoppers of SNAP-eligible households with young children (n 310)

Results:

Most participants reported first shopping for groceries online after the OPP was implemented (57 %). Families who purchased groceries in-store less frequently were less likely to report ever buying groceries online (rate ratio (RR): 0·66, 95 % CI 0·46, 0·93) compared with weekly grocery shoppers. Shoppers who intended to purchase more groceries online in the next 6 months were more likely to have online shopping experience, although this differed by timing of online grocery service adoption. Participants reported more negative attitudes towards in-store grocery shopping during the pandemic than prior to its onset and cited COVID-19 as a motivator for ordering groceries online in focus groups. Most participants who had shopped online planned to continue after the pandemic (79 %).

Conclusions:

Most participants who shopped online started during the COVID-19 pandemic and considered the pandemic a key motivator. Findings suggest that low-income households will continue to shop online, affirming the need for policies that promote equitable access to healthy food online.
Ignan Earths: Habitability of Terrestrial Planets With Extreme Internal Heating
Authors: Reinhold Matthew , Schaefer Laura
Published: January 2025

Is it possible for a rocky planet to have too much internal heating to maintain a habitable surface environment? In the Solar System, the best example of a world with high internal heating is Jupiter's moon Io, which has a heat flux of approximately 2 W compared to the Earth's 90 mW . The ultimate upper limit to internal heating rates is the Tidal Venus Limit, where the geothermal heat flux exceeds the Runaway Greenhouse Limit of 300 W for an Earth‐mass planet. Between Io and a Tidal Venus there is a wide range of internal heating rates whose effects on planetary habitability remain unexplored. We investigate the habitability of these worlds, referred to as Ignan Earth's. We demonstrate how the mantle will remain largely solid despite high internal heating, allowing for the formation of a convectively buoyant and stable crust. In addition, we model the long‐term climate of Ignan Earth's by simulating the carbonate‐silicate cycle in a vertical tectonic regime (known as heat‐pipe tectonics, expected to dominate on such worlds) at varying amounts of internal heating. We find that Earth‐mass planets with internal heating fluxes below 15 W produce average surface temperatures that Earth has experienced in its past (below 30C), and worlds with significantly higher heat fluxes still result in surface temperatures far below that of 100C, indicating a wide range of internal heating rates may be conducive with habitability.
Impact of Dust and Temperature on Primary Productivity in Late Miocene Oceans
Authors: Pillot Q. , Sarr A.‐C. , Donnadieu Y. , Gramoullé A. , Suchéras‐Marx B.
Published: January 2025

Most of the primary productivity in the ocean comes from phytoplankton, and is impacted, among other things, by the amount of nutrients available, as well as by temperature. The Late Miocene and Pliocene were marked by global aridification, linked to the emergence of the large deserts, likely increasing the input of dust and thus nutrients into the ocean. There was also a global decrease in temperature during this period, linked to a decline in atmospheric CO2 concentration. The objective of this study is to explore the sensitivity to dust and CO2 levels on primary productivity in the oceans under Late Miocene boundary conditions. Here we used simulations performed with the coupled ocean‐atmosphere model IPSL‐CM5A2 and its marine biogeochemistry component PISCES and a Late Miocene paleogeography. Our results show that an increase in dust input produces a quasi‐generalized increase in primary productivity, associated with a decrease in nutrient limitation. This increase in productivity also leads to nutrient deficits in some areas, such as coastlines and the Eastern Equatorial Pacific. The decrease in CO2 levels and the associated lower water temperatures lead to a reduction in primary productivity. This decrease is mainly due to a reduction in the supply of nutrients resulting from less intense remineralization. In addition, our results show that change in carbon export resulting from change in dust input and temperature are highly heterogeneous spatially. Simulations combined with sedimentary data suggesting a link between aridification, cooling and the Biogenic Bloom of the Late Miocene and Pliocene.
Nowcasting of a Warm‐Sector Rainfall Event in Southern China With the TRAMS Model: Sensitivity to Different Radar Reflectivity Retrieval Methods and Incremental Updating Strategies
Authors: Lin Xiaoxia , Feng Yerong , Jian Yuntao , Xu Daosheng , Huang Jincan , Chen Haowei , Zhang Banglin
Published: January 2025

To improve the radar data assimilation scheme for the high‐resolution Tropical Regional Atmospheric Model System (TRAMS) model, this study investigates the sensitivity of simulating a warm‐sector rainfall event in southern China to different radar reflectivity retrieval methods and incremental updating strategies. The findings indicate that the ice cloud retrieval (ICR) method yields more reasonable cloud hydrometeors. However, the impact of different retrieval methods is minimal without corresponding adjustments to the dynamic field. Further assimilation of the wind field effectively reduced the overestimated south winds and successfully simulated the observed low‐level convergence in northern Guangdong, significantly improving precipitation forecasts. Both incremental analysis update (IAU) and Nudging methods were able to adjust the forecast to better match the observations, with IAU performing slightly better. These findings are beneficial for further improving the forecast accuracy of precipitation intensity. Extending the IAU relaxation time from 4 to 10 min has almost no impact on the actual forecasting. However, prioritizing the adjustment of the wind field through time‐dependent IAU weighting factors, the impact of cloud particle adjustments on the dynamical field can be avoided (e.g., the drag caused by the sinking of cloud particles may offset the upward motion induced by dynamical convergence adjustments). This allows for more realistic low‐level wind convergence and precipitation forecasts to be obtained. Overall, the ICR method for retrieving cloud hydrometeors, combined with the IAU method using time‐dependent distribution weighting factors appears to be a more suitable option for the radar data assimilation scheme in TRAMS model.
Air Pollution and Cognitive Impairment Among the Chinese Elderly Population: An Analysis of the Chinese Longitudinal Healthy Longevity Survey (CLHLS)
Authors: Zhu Qingyang , Lyu Yuebin , Huang Keyong , Zhou Jinhui , Wang Wenhao , Steenland Kyle , Chang Howard H. , Ebelt Stefanie , Shi Xiaoming , Liu Yang
Published: January 2025

Cognitive impairment and dementia have long been recognized as growing public health threats. Studies have found that air pollution is a potential risk factor for dementia, but the literature remains inconclusive. This study aimed to evaluate the association between three major air pollutants (i.e., PM2.5, O3, and NO2) and cognitive impairment among the Chinese elderly population. Study participants were selected from the Chinese Longitudinal Health Longevity Survey (CLHLS) after 2005. We define cognitive impairment as a Chinese Mini‐Mental‐State Exam (CMMSE) score <24. The associations of air pollution with cognitive impairment and CMMSE score were evaluated with a logistic regression model and a linear mixed‐effect model with random intercepts, respectively. A total of 3,887 participants were enrolled in this study. Of the 2,882 participants who completed at least one follow‐up visit, 931 eventually developed cognitive impairment. In single‐pollutant models, we found that yearly average PM2.5 and NO2 as well as warm season O3, were positively associated with cognitive impairment. NO2 remained positively associated with cognitive impairment in the multi‐pollutant model. The linear mixed‐effect models revealed that warm season O3 and yearly average NO2 were significantly associated with decreased CMMSE scores. Our research has established a positive association between cognitive impairment and air pollution in China. These findings underscore the imperative for the next iteration of China's Air Pollution Prevention and Control Action Plan to broaden its focus to encompass gaseous air pollutants since mitigating single air pollutant is insufficient to protect the aging population.
Plausible Last Interglacial Antarctic Ice Sheet Changes Do Not Fully Explain Antarctic Ice Core Water Isotope Records
Authors: Zou Huiling , Sime Louise C. , Bertler Nancy A. N. , Keller Elizabeth D. , Wolff Eric W.
Published: January 2025

Antarctic ice cores can help determine ice mass loss from the Antarctic Ice Sheet (AIS) during past warm periods. We compile Last Interglacial (LIG) measurements from eight Antarctic cores and compare these to new isotope‐enabled LIG simulations, which explore three plausible LIG AIS elevation and extent scenarios. We find that these simulations capture less than 10% of East Antarctic core‐mean changes. Although our simulations do not fully explain the changes, they capture some inter‐core geographical variations. Some LIG AIS configurations show higher skill than PI AIS configurations in simulating the inter‐core differences. The remaining discrepancies between the simulated and observed core‐mean water isotope changes suggest that LIG simulations also need to include the influences of reduced Antarctic sea ice, a warmer Southern Ocean, and resultant shifts in vapor source regions to produce a more satisfactory match to observed at ice core sites.
The Process‐Oriented Understanding on the Reduced Double‐ITCZ Bias in the High‐Resolution CESM1
Authors: Dong Enze , Song Fengfei , Wu Lixin , Dong Lu , Wang Shengpeng , Liu Fukai , Wang Hong
Published: January 2025

The double‐Intertropical Convergence Zone (ITCZ) bias is a common model bias, which has puzzled the climate model community for several decades. Here, by comparing a high‐ and low‐resolution state‐of‐the‐art model CESM1, it is found that the double‐ITCZ bias is largely reduced in the high‐resolution CESM1. The key reason is the realistic colder sea surface temperature (SST) over the southeast Pacific (SEP) in the high‐resolution model. This realistic SEP SST is mainly due to a spuriously deeper mixed layer with a more realistic wind, as the sensitivity of mixed layer depth to wind is overestimated in both versions of CESM1. The better representation of terrain, such as Andes Mountains, elevates warm advection from inland to the coastal region, which maintains the inversion structure favorable for low cloud. The resultant increased coastal cloud in the high‐resolution CESM1 causes the colder coastal SST, thus improving the wind and deepening the mixed layer.
Seismic Wavefield Modeling of Enceladus: Challenges and Opportunities Presented by a 3D Ice Shell
Authors: Dapré K. , Irving J. C. E.
Published: January 2025

Understanding the interior structures of icy moons will be crucial in untangling narratives of formation and evolution, both within our solar system and beyond it. Seismology is a proven and unparalleled methodology for investigating the deep interiors of planetary bodies but has never been deployed on an icy moon. To improve future mission design, we conduct seismic simulations for Saturn's icy moon Enceladus which account for the unique seismic responses of icy ocean worlds. We discover that even with high surface temperatures at the south pole and 3D ice thickness models, seismic amplitudes are two orders of magnitude higher than the self‐noise of mission‐candidate instrumentation. We compare the effects of a 2D and 3D ice shell to determine the detail of seismic inversion for ice shell properties and how this varies with source and receiver location. We also compare the travel time differences caused by ice shell variation with potential effects from the uncertain core structure and discover that these two sources of travel time perturbation have similar magnitudes but could be distinguished through careful inversion strategy. We investigate varied source types to represent focal mechanisms likely to be present at the south pole of Enceladus. We finally make recommendations supporting landing sites between 20 and 30 from the south pole that should enable observation of a wide range of seismic phases, including core‐transmitted phases that could constrain core velocities.
Hot or Not? An Evaluation of Methods for Identifying Hot Moments of Nitrous Oxide Emissions From Soils
Authors: Stuchiner Emily R. , Xu Jiacheng , Eddy William C. , DeLucia Evan H. , Yang Wendy H.
Published: January 2025

Effectively quantifying hot moments of nitrous oxide (N2O) emissions from agricultural soils is critical for managing this potent greenhouse gas. However, we are challenged by a lack of standard approaches for identifying hot moments, including (a) determining thresholds above which emissions are considered hot moments, and (b) considering seasonal variation in the magnitude and frequency distribution of net N2O fluxes. We used one year of hourly N2O flux measurements from 16 autochambers that varied in flux magnitude and frequency distribution in a conventionally tilled maize field in central Illinois, USA, to compare three approaches to identify hot moment thresholds: standard deviations (SD) above the mean, 1.5x the interquartile range (IQR), and isolation forest (IF) identification of anomalous values. We also compared these approaches on seasonally subdivided data (early, late, and non‐growing seasons) versus the whole year. Our analyses revealed that 1.5x IQR method best identified N2O hot moments. In contrast, using 2 or 4 SD both yielded hot moment threshold values too high, and IF yielded threshold values too low, leading to missed N2O hot moments or low net N2O fluxes mischaracterized as hot moments, respectively. Furthermore, seasonally subdividing the data set not only facilitated identification of smaller hot moments in the late‐ and non‐growing seasons when N2O hot moments were generally smaller but it also increased hot moment threshold values in the early growing season when N2O hot moments were larger. Consequently, of the methods evaluated here, we recommend using the 1.5x IQR method on whole year data sets to identify N2O hot moments.
Activation of glutamine synthetase (GS) as a new strategy for the treatment of major depressive disorder and other GS-related diseases
Authors: Kang Jae Soon , Kim Hwajin , Baek Ji Hyeong , Song Miyoung , Park Hyeongchan , Jeong Wonjune , Chung Hye Jin , Yoo Dae Young , Lee Dong Kun , Park Sang Won , Kim Hyun Joon
Published: January 2025

Glutamine synthetase (GS) plays a crucial role in the homeostasis of the glutamate–glutamine cycle in the brain. Hypoactive GS causes depressive behaviors. Under chronic stress, GS has no change in expression, but its activity is decreased due to nitration of tyrosine (Tyr). Thus, we speculate that agents that prevent nitration or facilitate denitration of GS would be candidates for new antidepressants. Using human recombinant GS and mouse lysate from the medial prefrontal cortex, we demonstrated that Tyr (0.0313−0.5 µM) dose-dependently protected GS activity against peroxynitrite-induced Tyr-nitration of GS. Diet supplementation with Tyr exerted significant antidepressant effects in a chronic immobilization stress depression mouse model. We further found that dipeptides, such as tyrosyl-glutamine (YQ), that had appropriate chemical properties for medication also increased GS activity both in vitro and in vivo and exerted antidepressant effects. Because reduced GS activity also occurs in epilepsy and hyperammonemia, we evaluated whether Tyr and YQ had therapeutic effects. Interestingly, Tyr or YQ administration significantly attenuated kainic acid-induced seizures in mice and reduced blood ammonia levels in azoxymethane- or bile duct ligation-induced hyperammonemia mouse models, which was accompanied by an increment in GS activity. The activation of GS was accomplished by a decrement in Tyr-nitration, so-called Tyr-denitration. Therefore, this study demonstrates that the activation of GS could be a new strategy to treat depression and other GS-related diseases.
Double trouble: a comprehensive study into unrelated genetic comorbidities in adult patients with Facioscapulohumeral Muscular Dystrophy Type I
Authors: Puma Angela , Tammam Giulia , Ezaru Andra , Slioui Abderhmane , Torchia Eleonora , Tasca Giorgio , Villa Luisa , Cavalli Michele , Salviati Leonardo , van der Vliet Patrick J. , Lemmers Richard JLF , Pini Jonathan , van der Maarel Silvère M. , Sacconi Sabrina
Published: January 2025

Facioscapulohumeral dystrophy type 1 (FSHD1) displays prominent intra- and interfamilial variability, which complicates the phenotype-genotype correlation. In this retrospective study, we investigated FSHD1 patients classified as category D according to the Comprehensive Clinical Evaluation Form (CCEF), a category defined by FSHD patients showing uncommon clinical features, to identify genetic causes explaining these uncommon phenotypes. Demographics, clinical data and clinical scales of FSHD1 patients were retrospectively evaluated. Patients were divided into four CCEF categories, and comparisons between groups were performed. In category D, when uncommon features suggested the presence of an unrelated genetic disease, a more extensive collection of data was performed. 157 FSHD1 patients were included in the study (82 males, 75 females) with mean age of 52.1 ± 13.5 years at the time of the study. D4Z4 repeat sizes ranged between 2 and 10 RU. According to the CCEF, 114 patients were classified into category A, 8 into category B and C each, and 27 into category D. In category D, 9 patients presented uncommon features related to commonly acquired comorbidities, whereas in the remaining 18 patients, all but two with upper-sized FSHD1 D4Z4 repeats (7–10 RU), we suspected an unrelated genetic neurological disease based on clinical phenotype. In 14/18 patients, we identified FSHD-unrelated genetic causes, most often unrelated repeat expansion disorders. This emphasizes the need of careful clinical and genetic work-up to avoid confusion between FSHD-intrinsic clinical variability and clinical features unrelated to the disease.
Are metal-based antibacterial gels a potential alternative for disinfection in contemporary endodontics?
Authors: Murchie Bryan D. , Edwards David
Published: January 2025

Aims

This study aimed to assess the effectiveness of a novel antimicrobial gel, containing copper and silver nanoparticles, for use in root canal disinfection.

Methods

Copper and silver-based gels were created in-house, using a support network of biocompatible polymers, including polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), and polyethylene glycol (PEG). Six experimental groups were created, three containing silver ions and three copper ions, where the PVA, PVP and PEG ratios were also adjusted in each group to test the gel’s physical state. One control contained no metal nanoparticles. The gels surface characteristics, roughness, mechanical properties, and flowability, were characterised using a combination of atomic force microscopy, scanning electron microscopy, transmission electron microscopy and Rheometery. Further biological testing measured the gels cytotoxicity levels, using human periodontal ligament cells, and the anti-microbial effects against E. Faecalis and a multi-species bacteria biofilm.

Results

Each gel demonstrated high levels of viscosity, which was lowered in gels containing a reduced PVA concentration. The overall antimicrobial properties of the gels increased in those with a higher dissolution, lower porosity, and reduced surface roughness. Copper nanoparticles were shown to be significantly more effective against E. Faecalis, compared with silver. Gels containing higher PVA levels, and silver nanoparticles, had greater toxicity levels against human cells, however, testing was not possible for most experimental groups as the gels dissolved before measurements took place. The antimicrobial properties of all gel formulations were significantly less effective than sodium hypochlorite (after 1 h), but a similar outcome was detected in comparison with calcium hydroxide (after 7 days).

Conclusions

Developing an antimicrobial gel is highly dependent upon numerous compositional factors, where development is still at the early stages. The use of copper nanoparticles appeared to be more appropriate for use in canal disinfection, compared with silver that also had higher levels of human cell toxicity. The ratios selected for the biocompatible polymers had a critical impact on the physical state, antimicrobial, and toxicity levels. At present, antimicrobial gels are not as effective as sodium hypochlorite.
The burden of X-linked retinitis pigmentosa (XLRP) on patient experience and patient-reported outcomes (PROs): findings from the EXPLORE XLRP-2 study
Authors: Parmeggiani Francesco , Weber Michel , Bremond-Gignac Dominique , Daly Avril , Denee Tom , Lahaye Marjolein , Lotery Andrew , Paudel Nabin , Ritter Markus , Rodríguez de la Rúa Enrique , Rotenstreich Ygal , Sankila Eeva-Marja , Stingl Katarina , Van Denderen Jacqueline , Pungor Katalin
Published: January 2025

Background/aims

X-linked retinitis pigmentosa (XLRP) is considered one of the most severe forms of retinitis pigmentosa (RP), accounting for 5–15% of all RP cases and primarily affecting males. However, the real-world humanistic impacts of this disease on patients are poorly investigated, especially with respect to burdens faced by patients with varying disease severities.

Methods

EXPLORE XLRP-2 was an exploratory, multicentre, non-interventional study. A retrospective chart review was conducted to collect clinical/demographic data, including XLRP clinical stage (mild, moderate or severe). Cross-sectional surveys were used to gather experiences directly from patients by validated and modified patient-reported outcomes.

Results

176 patients with XLRP caused by retinitis pigmentosa GTPase regulator (RPGR) gene mutation were enrolled, of whom 169 were included in analyses. 81% of patients were male, mean (SD) age was 39.3 (17.61) years, and 20 adolescents were included. Mean age (SD) at genetic confirmation was 33.4 years (17.98), and the mean duration (SD) from initial symptoms to genetic diagnosis was 16.4 (15.66) years. Compared with patients with mild disease, patients with severe XLRP are more likely to experience difficulties with functioning in low luminance, depression, unemployment, productivity issues, mobility and daily activities.

Conclusion

This is the first real-world study to collect data directly from patients on the burden of XLRP and to correlate that burden with disease stage. As a result, several areas of significant burden, especially for patients with severe disease, have been identified that should provide focus for future public policies and therapeutic prospects.
Safety and efficacy of supraciliary dexamethasone implantation for macular oedema: a preliminary comparative study
Authors: Doganay Selim , Ucan Gunduz Gamze , Kiristioglu Mehmet Omer , Demirel Elif , Yalcinbayir Ozgur
Published: January 2025

Purpose

To evaluate the efficacy and safety of dexamethasone implantation in the supraciliary (SC) space, a novel and potential effective implantation site, compared to intravitreal (IV) application.

Methods

This prospective study included 39 eyes of 38 patients with macular oedema (ME) who underwent SC and IV dexamethasone implantation (SC-DEX and IV-DEX). Patients were randomly assigned to treatment groups and followed for 3 months. Preoperative and postoperative assessments included maximum retinal thickness (MRT), change in central retinal thickness between consecutive visits (ΔCRT), intraocular pressure (IOP), and best corrected visual acuity (BCVA).

Results

Both SC-DEX and IV-DEX groups showed significant MRT reductions during at follow-up. In the SC group, MRT significantly decreased at 1st and 3rd months (p = 0.0002 for both), but not at 1st week (p = 0.2517). In the IV-DEX group, significant reductions in MRT were observed at all postoperative visits: 1st week (p = 0.0002), 1st month (p = 0.0004), and 3rd month (p = 0.0003). There were no significant differences in the change in ΔCRT between the SC-DEX and IV-DEX groups at any visit (p > 0.05). IOP did not show significant changes (p > 0.05). BCVA improved significantly in the SC group compared to the IV-DEX group during the first week (p = 0.014). No other perioperative or postoperative sight-threatening complications were noted in either group, including hypotony or endophthalmitis.

Conclusion

SC-DEX shows promise as an alternative for managing ME, offering similar effectiveness to IV-DEX with safe profile. Further studies are needed to confirm its long-term safety and efficacy.
UnidecNMR: automatic peak detection for NMR spectra in 1-4 dimensions
Authors: Buchanan Charles , Karunanithy Gogulan , Tkachenko Olga , Barber Michael , Marty Michael T. , Nott Timothy J. , Redfield Christina , Baldwin Andrew J.
Published: January 2025

To extract information from NMR experiments, users need to identify the number of resonances in the spectrum, together with characteristic features such as chemical shifts and intensities. In many applications, particularly those involving biomolecules, this procedure is typically a manual and laborious process. While many algorithms are available to tackle this problem, their performance tends to be inferior to that of an experienced user. Here, we introduce UnidecNMR, which identifies resonances in NMR spectra using deconvolution. We demonstrate its favourable performance on 1 and 2D simulated spectra, strongly overlapped 1D spectra of oligosaccharides and 2D HSQC, 3D HNCO, 3D HNCA and 3/4D methyl-methyl NOE experimental spectra from a range of proteins. UnidecNMR outperforms a number of freely available algorithms and provides results comparable to those generated manually. Introducing additional restraints, such as a 2D peak list when analysing 3 and 4D data and incorporating reflection symmetry in NOE analysis further improves the results. UnidecNMR outputs a back-calculated spectrum and a peak list, both of which can be easily examined using the supplied GUI. The software allows interactive processing using nmrPipe, allowing users to go directly from raw data to processed spectra with picked peak lists.
Inferring effects of mutations on SARS-CoV-2 transmission from genomic surveillance data
Authors: Lee Brian , Quadeer Ahmed Abdul , Sohail Muhammad Saqib , Finney Elizabeth , Ahmed Syed Faraz , McKay Matthew R. , Barton John P.
Published: January 2025

New and more transmissible variants of SARS-CoV-2 have arisen multiple times over the course of the pandemic. Rapidly identifying mutations that affect transmission could improve our understanding of viral biology and highlight new variants that warrant further study. Here we develop a generic, analytical epidemiological model to infer the transmission effects of mutations from genomic surveillance data. Applying our model to SARS-CoV-2 data across many regions, we find multiple mutations that substantially affect the transmission rate, both within and outside the Spike protein. The mutations that we infer to have the largest effects on transmission are strongly supported by experimental evidence from prior studies. Importantly, our model detects lineages with increased transmission even at low frequencies. As an example, we infer significant transmission advantages for the Alpha, Delta, and Omicron variants shortly after their appearances in regional data, when they comprised only around 1-2% of sample sequences. Our model thus facilitates the rapid identification of variants and mutations that affect transmission from genomic surveillance data.
Morphometry and mechanical instability at the onset of epithelial bladder cancer
Authors: Lampart Franziska L. , Vetter Roman , Yamauchi Kevin A. , Wang Yifan , Runser Steve , Strohmeyer Nico , Meer Florian , Hussherr Marie-Didiée , Camenisch Gieri , Seifert Hans-Helge , Rentsch Cyrill A. , Le Magnen Clémentine , Müller Daniel J. , Bubendorf Lukas , Iber Dagmar
Published: January 2025

Malignancies of epithelial tissues, called carcinomas, account for most cancer cases. Research has largely focused on correlating different carcinoma subtypes to genetic alterations. However, as well as a rewiring in the signalling networks, carcinoma progression is accompanied by mechanical changes in the epithelial cells and the extracellular matrix. Here we reveal intricate morphologies in the basement membrane at the onset of bladder cancer and propose that they emerge from a mechanical instability upon epithelial overgrowth. We imaged mouse and human bladder tissue and performed differential growth simulations, and found that stiffness changes in the different mucosa layers can result in aberrant tissue morphologies. The resulting thickening, wrinkles and folds resemble early papillary tumours and carcinomas in situ. Atomic force microscopy confirmed local stiffness changes in the pathological basement membrane. Our findings suggest a possible mechanical origin of the different bladder carcinoma subtypes and may guide future developments in treatment and prophylaxis.
Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial
Authors: Vitanza Nicholas A. , Ronsley Rebecca , Choe Michelle , Seidel Kristy , Huang Wenjun , Rawlings-Rhea Stephanie D. , Beam Madison , Steinmetzer Leonel , Wilson Ashley L. , Brown Christopher , Beebe Adam , Lindgren Catherine , Gustafson Joshua A. , Wein Amy , Holtzclaw Susan , Hoeppner Corrine , Goldstein Hannah E. , Browd Samuel R. , Hauptman Jason S. , Lee Amy , Ojemann Jeffrey G. , Crotty Erin E. , Leary Sarah E. S. , Perez Francisco A. , Wright Jason N. , Alonso Marta M. , Dun Matthew D. , Foster Jessica B. , Hurst Diana , Kong Ada , Thomsen Alison , Orentas Rimas J. , Albert Catherine M. , Pinto Navin , Annesley Colleen , Gardner Rebecca A. , Ho On , Pattabhi Sowmya , Gust Juliane , Wendler Jason P. , Park Julie R. , Jensen Michael C.
Published: January 2025

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG. The primary objectives were to assess feasibility and tolerability, which were both met. Secondary objectives included assessments of CAR T cell distribution and survival. A total of 23 patients with DIPG enrolled, and 21 were treated with repeated doses of ICV B7-H3 CAR T cells using intra-patient dose-escalation regimens without previous lymphodepletion. Concurrent tumor-directed therapy, including re-irradiation, was not allowed while on protocol therapy. We delivered a total of 253 ICV doses and established the highest planned dose regimen, DR4, which escalated up to 10 × 107 cells per dose, as the maximally tolerated dose regimen. Common adverse events included headache, fatigue and fever. There was one dose-limiting toxicity (intratumoral hemorrhage) during DR2. For all treated patients (n = 21), the median survival from their initial CAR T cell infusion was 10.7 months and the median survival from diagnosis was 19.8 months with 3 patients still alive at 44, 45 and 52 months from diagnosis. Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial. ClinicalTrials.gov registration: NCT04185038.
Hydrocarbon potential in the Northern Egyptian Red Sea: insights from geophysical datasets and analysis of onshore marginal outcrop analogues and subsurface sequences
Authors: Noureldin Ahmed M. , Hassan Mustafa , Farouk Mohamed , Mabrouk Walid M. , Radwan Ahmed E. , Metwally Ahmed
Published: January 2025

The Red Sea remains a largely under-explored basin, with the Northern Egyptian Red Sea requiring further investigation due to limited borehole data, sparse case studies, and poor seismic quality. A petroleum system, regional structural cross-section, and geological block diagrams integrating onshore fieldwork from Gebel Duwi and offshore subsurface geology were utilized to assess the hydrocarbon potential of the Northern Egyptian Red Sea (NERS). The findings highlight that pre- and syn-rift organic-rich source units in the NERS could generate oil and gas, similar to the capped reservoirs of the Southern Gulf of Suez. The study also reveals that both regions (NERS and SGOS) were influenced by the Levant-Aqaba transform fault influenced both regions (NERS and SGOS), resulting in southwest-dipping strata, replicating the Northern Gulf of Suez structural style. Additionally, rifting extended the rotated basement faulted blocks from the shoreline to the axial trough, creating wedged Miocene sections. Most offshore boreholes in the Red Sea bottomed in Precambrian rock directly below the syn-rift Miocene sequence, suggesting these wells were off-structure, similar to sidetracked wells in the Gulf of Suez, which successfully captured thick pre- and syn-rift sediments. These insights can drive further advancements in hydrocarbon exploration in the Northern Egyptian Red Sea.
Ovario- protective effect of Moringa oleifera leaf extract against cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats
Authors: Soliman Seham Samir , Suliman Ahmed A. , Fathy Khaled , Sedik Ahmed A.
Published: January 2025

It is crucial to develop new tactics to prevent ovarian tissue damage in women whose reproductive toxicity is caused by chemotherapy. The present investigation was performed to assess the protective effects of Moringa oleifera (M. oleifera) leaf extract on cyclophosphamide (CP)-induced ovarian damage and reproductive dysfunction. Thirty-two female, healthy Wistar albino rats were randomly assigned to four groups (8 rats/group). The first group was given saline intraperitoneally (i.p.). The second group was given a single dose of CP (200 mg/kg; i.p.). The third and fourth groups were given M. oleifera leaf extract (150 and 250 mg/kg; orally) for 20 days before receiving CP on the final day of the experiment. Hormonal assessments, including follicle stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (ES), were performed 24 h after CP administration. In addition, the antioxidant status and inflammatory response against CP were evaluated. Moreover, detailed histopathological and ultra- structural observations were conducted. For evaluation of statistical significance between different groups; One-way analysis of variance (ANOVA) with Tukey’s post hoc test was adopted. Our findings revealed that rats subjected to CP showed increased levels of FSH, LH, malondialdehyde (MDA), tumor necrosis factor-alpha, and interleukin-8 and decreased levels of ES and glutathione. Pre-treatment with M. oleifera leaf extract (250 mg/kg; orally) was statistically significant (p values < 0.05) as it could improve hormonal changes, oxidative stress indices, and pro- inflammatory mediator levels. Consequently, a marked improvement was observed in the ovarian and uterine architectures, with a normal ovarian reserve and a normal endothelium with normal tubular glands. In conclusion, M. oleifera leaf extract (250 mg/kg) could be used as a pharmaceutical supplement because it protects female rats against CP-induced ovarian damage and reproductive dysfunction.
Patterns and implications of spatial covariation in herbivore functions on resilience of coral reefs
Authors: Cook Dana T. , Holbrook Sally J. , Schmitt Russell J.
Published: January 2025

Persistent shifts to undesired ecological states, such as shifts from coral to macroalgae, are becoming more common. This highlights the need to understand processes that can help restore affected ecosystems. Herbivory on coral reefs is widely recognized as a key interaction that can keep macroalgae from outcompeting coral. Most attention has been on the role ‘grazing’ herbivores play in preventing the establishment of macroalgae, while less research has focused on the role of ‘browsers’ in extirpating macroalgae. Here we explored patterns, environmental correlates and state shift consequences of spatial co-variation in grazing and browsing functions of herbivorous fishes. Grazing and browsing rates were not highly correlated across 20 lagoon sites in Moorea, French Polynesia, but did cluster into 3 (of 4) combinations of high and low consumption rates (no site had low grazing but high browsing). Consumption rates were not correlated with grazer or browser fish biomass, but both were predicted by specific environmental variables. Experiments revealed that reversibility of a macroalgal state shift was strongly related to spatial variation in browsing intensity. Our findings provide insights and simple diagnostic tools regarding heterogeneity in top-down forcing that influences the vulnerability to and reversibility of shifts to macroalgae on coral reefs.