bluuebunny/crossref_metadata_2025 huggingface dataset:
Aesthetic Outcome of Isolated Advancement Genioplasty With and Without Submental Liposuction in the Treatment of Skeletal Chin Deficiency in Double Chin Patients (A Randomized Controlled Clinical Trial)
Authors: Atef Marwan M. , Sholkamy Hisham , Khashaba Mohammed M. , Behairy Galal , Ellabban Mohamed A.
Published: December 2024

This study was conducted to evaluate the effect of submental liposuction with advancement genioplasty versus advancement genioplasty alone on esthetics in double chin patients. Twenty-six patients with deficient chin were included in the study. The patients were distributed into 2 groups: submental fat liposuction in conjunction with advancement genioplasty group as intervention one and advancement genioplasty alone as a control group. Preoperative and postoperative computed tomography was performed for all patients. With the help of various software, diagnosis, virtual planning, and evaluation were done. Patient satisfaction was evaluated by a Face-Q questionnaire. The study was conducted on 26 patients with deficient chin, 88.9% were females and 11.1% were males. The mean age of cases was (25.5±3.5 y), clinically all cases went uneventful, and there were no statistically significant differences regarding soft tissue relapse between the study and control groups. All patients showed statistically significant increases in scores of satisfaction with the chin, psychological well-being, and social well-being scales. Submental fat liposuction can be a good intervention choice in mild-moderate chin deficient cases when added to an advanced genioplasty procedure.
Oral Rehabilitation After Maxillary Protraction With Skeletal Anchorage in a Patient With Oligodontia
Authors: Buyukcavus Muhammed Hilmi , Sari Ömer Faruk , Buyukcavus Esra
Published: December 2024

Objective:

To evaluate the outcomes of skeletal anchorage-supported maxillary protraction and prostetic restoration in a patient with class III malocclusion and hypodontia.

Methods:

Anchorage plates were placed in the apertura piriformis region as skeletal anchorage support. Subsequently, 500 g orthopedic force per side was applied for maxillary protraction. After protraction, fixed orthodontic treatment corrected the tooth spaces and occlusion. It was made ready for prosthetic restoration. The active treatment process lasted 23 months. After 3 years, long-term follow-up checks were performed and prosthetic restorations were completed.

Results:

Following treatment, the SNA angle [Angle between cranial base (SN) and point A] increased by 2.96 degrees, and the SN/GoGn [Angle between cranial base (SN) and mandibular plane] angle increased by 0.18 degrees. The SNB [Angle between cranial base (SN) and point B] and FMA angles [Angle between Frankfurt horizontal plane and mandibular plane] decreased by 2.28 degrees and 0.79 degrees, respectively. The overjet increased by 6.35 mm. As a result of long-term follow-up, the results were seen to be stable, and ideal smile aesthetics and occlusion were achieved with prosthetic restorations.

Conclusion:

Skeletal anchorage-supported protraction treatments in class III malocclusion with insufficient dental support lead to significant improvements in profile and facial appearance.
Impact of American College of Surgeons Geriatric Surgery Verification Program in Patients Undergoing Major Abdominal Oncologic Operation at a Cancer Center
Authors: Jimenez Mercy , Salehi Omid , Somasundar Ponnandai , Dandeneau Jayme , Chebl Joanna , Vognar Lidia , Espat N Joseph , Calvino Abdul Saied , Kwon Steve
Published: December 2024

BACKGROUND:

Patients older than 65 years have unique needs and treatment outcomes goals. The objective of this study was to evaluate the impact of Geriatric Surgery Verification (GSV) initiative in oncology patients ≥65 years undergoing major abdominal surgeries.

STUDY DESIGN:

We implemented the American College of Surgeons’ GSV program protocols for patients 65 and older starting in 2022. A retrospective review was conducted of patients undergoing major abdominal oncologic surgeries from January 2021 through December 2022 to create pre-GSV and post-GSV initiative cohorts. Main outcomes variables were postoperative institutionalization and change in the patient's primary residence disposition (measured as primary residence score, PRS, as a proxy for loss of independence).

RESULTS:

57 patients in the control group and 43 patients in the intervention group met inclusion criteria. The average age was 76.5 and 75 years, respectively. Patients were well matched for clinical and sociodemographic characteristics. The intervention group had a shorter mean length of stay (LOS) 4.4 ± 2.5 days vs 6.5 ± 3.6 days in control group (p<.01) and were less likely to be newly discharged to an institution (7.3% vs 24.1%, p=0.03). The GSV initiative was associated with 72% lower odds of increased PRS (i.e. care needs) at time of discharge (OR 0.28, 95% CI 0.1 – 0.81).

CONCLUSION:

The GSV initiative intervention in geriatric oncology patients undergoing major abdominal surgeries was associated with reducing postoperative institutionalization and change in primary residence disposition. Further studies to explore different mechanisms within GSV that lead to improved outcomes in geriatric oncologic population will be informative.
Dysregulation of cellular iron predisposes chemotherapy resistant cancer cells to ferroptosis
Authors: Loftus Luke V. , Rolle Louis T.A. , Cherry Christopher , Patatanian Michael , Orzolek Linda , Wang Bowen , Pienta Kenneth J. , Amend Sarah R.
Published: December 2024

Despite centuries of research, metastatic cancer remains incurable due to resistance against all conventional cancer therapeutics. Alternative strategies leveraging non-proliferative vulnerabilities in cancer are required to overcome cancer recurrence. Ferroptosis is an iron dependent cell death pathway that has shown promising pre-clinical activity in several contexts of therapeutic resistant cancer. However, ferroptosis sensitivity is highly variable across tissue types and cell state posing a challenge for clinical translation.

We describe a convergent phenotype induced by chemotherapy where cells surviving chemotherapy have similar transcriptomic signatures and dysregulated iron homeostasis, regardless of initial cell type or chemotherapy used. Elevated labile iron levels are counteracted by NRF2 signaling that does not alleviate the amount of labile iron. Selectively inhibiting GPX4 leads to uniform susceptibility to ferroptosis in surviving cells, highlighting the common reliance on lipid peroxidation defenses. Cellular iron dysregulation is a vulnerability of chemoresistant cancer cells that can be leveraged by triggering ferroptosis.

STATEMENT OF SIGNIFICANCE

We show that cells surviving chemotherapy are uniformly sensitive to ferroptosis, despite different sensitivity in untreated cells. Ferroptosis sensitivity surprisingly occurs alongside NRF2 signaling, likely due to loss of PCBP1 and accumulated labile iron. Labile iron accumulation as a driver of ferroptosis sensitivity constitutes another starting point for translation of ferroptosis.
Controlled “out-of-season” spawning of reef-forming corals in aquaria using offset environmental profiles
Authors: Koukoumaftsis Lonidas P. , Salmon Matthew , Everson Glenn , Hughes David J. , Varkey Deepa , Heyward Andrew J. , Severati Andrea , Humphrey Craig
Published: December 2024

The global climate crisis has heightened the urgency for developing interventions to enhance resilience and recovery of coral reef ecosystems. However, research programs are often bottlenecked by availability of coral early life stage material due to the seasonal (annual) nature of coral mass spawning events. Here, we present a proof-of-concept of “out-of-season” coral spawning, utilising advanced aquarium control technology to induce spawning in multiple key Great Barrier Reef (GBR) coral species held in long-term indoor aquaria. By developing a 6-month offset environmental profile encompassing seasonal temperature, photoperiod, and lunar profiles, we successfully induced synchronised mass coral spawning during austral autumn/winter (May - June) over consecutive years in 2022 and 2023. We also “phase-shifted” the hour of sunset by five hours on spawning nights, creating a more favourable time window (i.e., minimising late nights) for gamete fertilisation. The timing of gamete release in captive corals closely matched previous GBR field observations for both nights after full moon (NAFM) and time after sunset (TAS). Gamete fertilisation was successful for six GBR species:Acropora millepora, Acropora loripes, Acropora hyacinthus, Acropora elseyi, Acropora austera,andMontipora aequituberculataproducing a total of 1.75 million larvae. We outline key physiological insights gained into environmental regulation of coral spawning synchronicity and discuss the potential for out-of-season spawning to accelerate various aspects of coral reproduction research and enhance the growing toolbox of active restoration strategies aimed at reversing global coral reef decline.
GM-CSF engages multiple signaling pathways to enhance pro-inflammatory cytokine responses in human monocytes duringLegionellainfection
Authors: Vázquez Marrero Víctor R. , Dresler Madison , Haggadone Mikel D. , Lu Allyson , Shin Sunny
Published: December 2024

The proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for host defense against a wide range of pathogens. We previously found that GM-CSF enhances inflammatory cytokine production in murine monocytes and is required forin vivocontrol of the intracellular bacterial pathogenLegionella pneumophila. It is unclear whether GM-CSF similarly augments cytokine production in human monocytes during bacterial infection.

Here, we find that GM-CSF enhances inflammatory cytokine expression inLegionella-infected human monocytes by engaging multiple signaling pathways.Legionella- and TLR-dependent NF-𝜅B signaling is a prerequisite signal for GM-CSF to promote cytokine expression. Then, GM-CSF-driven JAK2/STAT5 signaling is required to augment cytokine expression inLegionella-infected human monocytes. We also found a role for PI-3K/Akt/mTORC1 signaling in GM-CSF-dependent upregulation of cytokine expression. Finally, glycolysis and amino acid metabolism are also critical for GM-CSF to boost cytokine gene expression in human monocytes during infection. Our findings show that GM-CSF-mediated enhancement of cytokine expression in infected human monocytes is regulated by multiple signaling pathways, thereby allowing the host to fine tune antibacterial immunity.
Tactile stimulations reduce or promote the segregation of auditory streams: psychophysics and modelling
Authors: Darki Farzaneh , Rankin James , Słowiński Piotr
Published: December 2024

Auditory stream segregation plays a crucial role in understanding the auditory scene. This study investigates the role of tactile stimulation in auditory stream segregation through psychophysics experiments and a computational model of audio-tactile interactions. We examine how tactile pulses, synchronized with specific tones in a sequence of interleaved high- and low-frequency tones (ABA-triplets), influence the likelihood of perceiving integrated or segregated auditory streams. Our findings reveal that tactile pulses synchronized with specific tones enhance perceptual segregation, while pulses synchronized with both tones promote integration. Based on these findings, we developed a dynamical model that captures interactions between auditory and tactile neural circuits, including recurrent excitation, mutual inhibition, adaptation, and noise. The proposed model shows excellent agreement with the experiment. Model predictions are validated through psychophysics experiments. In the model, we assume that selective tactile stimulation dynamically modulates the tonotopic organization within the auditory cortex. This modulation facilitates segregation by reinforcing specific tonotopic responses through single-tone synchronization while smoothing neural activity patterns with dual-tone alignment to promote integration. The model offers a robust computational framework for exploring cross-modal effects on stream segregation and predicts neural behaviour under varying tactile conditions. Our findings imply that cross-modal synchronization, with carefully timed tactile cues, could improve auditory perception with potential applications in auditory assistive technologies aimed at enhancing speech recognition in noisy settings.
Blood flow simulation and uncertainty quantification in extensive microvascular networks: Application to brain cortical networks
Authors: Rasmussen Peter Mondrup
Published: December 2024

Spatially resolved simulation models of microcirculatory blood flow facilitate a detailed understanding of microcirculatory phenomena at the micrometer scale by capturing heterogeneity in blood flow. These models combine physical laws, empirical descriptions of the blood's complex rheological behavior, and in-vivo/ex-vivo imaging of the microvasculature. However, imaged areas often only partially represent self-contained tissue regions, leading to numerous vessels crossing boundaries and strongly influencing simulated blood flows through imposed boundary conditions. Selecting appropriate boundary conditions is challenging due to the heterogeneity of pressures and blood flows, resulting in significant uncertainties. This study addresses two key methodological aspects of spatially resolved blood flow simulations: selecting appropriate boundary conditions and quantifying the impact of boundary condition uncertainties on simulated hemodynamic variables. An adaptive method for assigning appropriate pressure boundary conditions is proposed and rigorously evaluated in extensive brain cortical networks against reference data from an established blood flow simulation model. A probabilistic approach is adopted to assess the impact of boundary condition uncertainties on blood flow simulations. The adaptive method is further integrated into a Bayesian calibration framework, inferring distributions over thousands of unknown pressure boundary conditions and providing uncertainty estimates for blood flow simulations. The adaptive method, which is straightforward to implement and scales well with extensive microvascular networks, produces hemodynamic simulations consistent with reference data, yielding depth-dependent pressure profiles and layer-wise capillary blood flow profiles consistent with previous studies. These phenomena are demonstrated to generalize also to biphasic blood flow simulation models incorporating in-vivo viscosity formulations. The uncertainty analysis further reveals a novel spatially heterogeneous and depth-dependent pattern in blood flow uncertainty. It is anticipated that the adaptive method for pressure boundary conditions will be useful in future applications of both forward and inverse blood flow modeling, and that uncertainty quantification will be valuable in complementing hemodynamic predictions with associated uncertainties.
Good fire: quantifying the beneficial ecosystem work of western U.S. wildfires (2010-2020)
Authors: Balch Jennifer K. , McIntosh Tyler L. , Illangakoon Nayani T. , Cummins Karen , Varner J. Morgan , Hansen Winslow D. , Marquis Kate Dargan , Raymond Crystal L. , Harvey Brian J. , Platt Rutherford V.
Published: December 2024

Wildfires are doing necessary work for western US forests that have evolved with fire. Here we define “good fire” as areas that burn in an ecologically beneficial way, with a severity that is analogous to their historical fire regimes prior to European settlement. We focus on low-moderate severity wildfire as this type of burning can promote regeneration, even in the context of a warming climate (Davis et al., 2023). We quantify the amount of forested area (i.e., deciduous, conifer, or mixed forest types) burned in low-moderate severity good fire and compare that to the amount of forested area that received prescribed burns (2010-2020). Our results show that 50% of the forested area burned by wildfires in the western US burned as low-moderate severity good fire. Moreover, the total area of this type of good fire was 3.3 million ha for wildfires (N = 18,126 events), compared with 2.7 million ha for forested prescribed burning (N = 25,761 events) over this same period. Lower severity wildfires are doing important work to promote healthy forests, 23% more by area than accomplished through prescribed burning. We also quantified high severity good fire in systems that historically experienced stand replacement, which represents an additional 10% of the forest area burned. Knowing that fires are likely going to increase in frequency and area with warming (Stephens et al., 2023), our key challenge in the future will be promoting good fire while still protecting lives and property.
Regulation of XPG-DNA damage binding dynamics by pre- and post-incision nucleotide excision repair factors and EXO1
Authors: Muniesa-Vargas Alba , Ribeiro-Silva Cristina , Geverts Bart , Davó-Martínez Carlota , van de Grint Jacinta , Ganpat Maroussia , Thijssen Karen L. , Pothof Joris , Houtsmuller Adriaan B. , Theil Arjan F. , Vermeulen Wim , Lans Hannes
Published: December 2024

The XPG endonuclease plays a crucial role in nucleotide excision repair (NER) and other genome maintenance pathways. Precise regulation of XPG recruitment and activity during DNA repair is essential to avoid erroneous DNA incisions and genomic instability. In this study, we employed live-cell imaging to investigate how XPG function is regulated during NER, focusing on its dynamic interactions with key factors involved in the pre- and post-incision steps. We found that TFIIH and XPA facilitate the recruitment and association of XPG with DNA damage, and that XPG localizes separately from TFIIH to UV-induced lesions. Furthermore, our results show that XPG’s dissociation from DNA damage is triggered by its own incision activity as well as by that of XPF. Additionally, the exonuclease EXO1 promotes XPG dissociation, likely by processing incised DNA, even in the absence of XPG-mediated incision. Our findings help to better understand the regulatory mechanisms that control XPG activity during NER and provide important insights into the complex dynamics of the repair process.
FedPyDESeq2: a federated framework for bulk RNA-seq differential expression analysis
Authors: Muzellec Boris , Marteau-Ferey Ulysse , Marchand Tanguy
Published: December 2024

Despite opportunities for deeper clinical insights, large-scale transcriptome studies are often limited by data silos and risks of privacy leakage. While meta-analysis can be employed to aggregate local results, this is at the price of lower statistical power, especially in heterogeneous settings. A recent paradigm in distributed computing, federated learning (FL) is a means of fitting models from siloed data, while ensuring that private data does not leave its storage facilities. Here, we introduce FedPyDESeq2, a software for differential expression analysis (DEA) on siloed bulk RNA-seq. Building on FL tools,FedPyDESeq2implements theDESeq2pipeline for DEA on siloed datasets in a privacy-enhancing manner. We benchmarkFedPyDESeq2on datasets from The Cancer Genome Atlas corresponding to 8 different indications, split by geographical origin.FedPyDESeq2achieves near-identical results on siloed data compared withDESeq2on pooled data, and significantly outperforms meta-analysis baselines on siloed data.
Convincing Evidence of Carnivorous Diet in Alvarezsaurian Dinosaur
Authors: Wang Shuo , Ding Nuo , Ma Waisum , Yu Wenmiao , Zheng Tingting , Choiniere Jonah , Xu Xing
Published: December 2024

A dietary shift from carnivory to insectivore has been proposed to explain the dramatic morphological evolution of alvarezsaurians, particularly the adaptation related to the manual digital reduction and body size miniaturization. However, based solely on morphological shifts, this hypothesis lacked direct dietary evidence to support either carnivory or insectivore. Here, we present the first convincing dietary evidence for alvarezsaurians, derived from the intestinal contents of the Early CretaceousBannykus wulatensis. Our analysis revealed significantly higher levels of calcium and phosphorus in the intestinal contents compared to the surrounding sandstone. Scanning electron microscopy identified hard tissue debris and possible soft tissues surrounding by phosphatized bacteria and tightly packed hollow microspheres, suggesting that the intestinal contents were strongly pseudomorphed by phosphatized microbes during fossilization. Raman spectroscopy showed characteristic peaks indicative of bone-derived material, consistent with the hard tissue debris appeared in the intestinal contents. Our results suggest thatBannykushad a carnivorous diet with strong chemical digestion, which likely compensated for its delicate cranial structures and small teeth. These results imply that if a dietary shift to insectivore occurred, it likely took place later in alvarezsaurian evolution, probably coinciding with a reduction in body size.
COMPETENCES OF LOWER COMMUNITY HEALTH CENTRE LEADERS IN ANNUAL HEALTH WORK PLANS AND ITS INFLUENCE ON DISTRICT PERFORMANCE IMPROVEMENT IN BUSOGA SUB-REGION: A RETROSPECTIVE STUDY
Authors: Muluya Kharim Mwebaza , Muwanguzi Gangu David , Babatunde Aremu , Rashid Naziru , Wananda Irene , Kayemba Jonah Fred , Ogara Collin , Waibi Musa , Mugisha John Francis , Waiswa Peter
Published: December 2024

Background

Lower-level community health centres play a crucial role in the delivery of primary healthcare services, and the competences of their leaders can significantly influence district health performance.

Objective

The study assessed the influence of competences of lower community health centre leaders in annual health work planning on the district performance improvement. Staffs are recruited based on staffing standards and expected to participate in district health planning cycles, and use implementation manuals in developing annual health work plans to improve district health performance.

Methods

A retrospective (case control) study design was employed to understand health centre performance data across various districts in the Busoga sub-region. There was a comparison of performance between the worst performing (case) and best performing (control) districts in the region according to the Annual Health Sector Performance reports from 2017/18 financial year to 2021/2022. Data was collected between 17thJuly, 2024 and 23rdAugust, 2024. Statistical analysis of data from 12 health centres in the case and 12 in the control was conducted using STATAversion 16to determine competences of lower community health centre leaders that influence district performance.

Results

The study found that the district performance in annual health work planning was not good in both the case and control groups (26.4% and 47.2% respectively). Only three competences variables were statistically significantly associated with improved district health performance. Health centres that (1) met staffing levels in accordance with public facility standards (χ2, 7.756;p-value, 0.005*), (2) staff attended district planning cycle meetings (χ216.713;p-value, 0.001*), and (3) health centres utilized four or more implementation manuals for the development of their annual health work plans (χ243.333;p-value, 0.001*) demonstrated statistically significant improvements in performance. These competences enabled more effective service delivery, better alignment with district health priorities, and the implementation of comprehensive, evidence-based interventions.

Conclusion

The competences of lower community health centre leaders is held together with health centres meeting staffing standards, their participation in district planning cycles, and the utilization of implementation manuals and are critical for improving district health performance in the Busoga sub-region. Strengthening these competences through targeted supportive meetings and capacity-building initiatives is recommended to enhance the overall effectiveness of health service delivery at the district level.
The two crystal structures of unloaded and cargo-loaded Vacuolar Sorting Receptor 1 lumenal domain (VSR1-Nt) reveal two cargo binding sites and a mechanism of transport
Authors: Borges Rafael J. , Eldahshoury Mahmoud K. , Parr Rebecca J. , Paul Marilyn , Fyfe Paul , Nettleship Joanne E. , An Jing , Shah Nita , Loureiro Levada Ana J. , Fontes Marcos R. M. , Owens Raymond J. , Denecke Jurgen , Quigley Andrew , Goldman Adrian , Postis Vincent , Usón Isabel , de Marcos Lousa Carine
Published: December 2024

Vacuolar sorting receptors (VSRs) are type I membrane proteins crucial for seed germination and plant development. While VSR trafficking has been extensively studied, the mechanism of cargo binding and release by the N-terminal lumenal region is less understood. We have elucidated the crystal structures of unloaded and cargo-loaded forms of the lumenal region of VSR1 containing the protease-associated domain, the Central domain and epidermal growth factor-like repeats. Calcium coordination induces remodeling of the linkers between domains, triggering large conformational changes that expose two binding sites, one across the PA and Central domain and a second site in the Central domain. Our findings provide a mechanistic model for cargo binding in a calcium rich environment, where VSR is locked in a conformation exposing the cargo binding sites, while cargo release is favoured by lower calcium concentrations and trimer formation. These results advance our current knowledge on VSRs and will inform future studies on vacuolar trafficking and cargo binding/release.
Genomic Epidemiology of 2023-2024 Oropouche Outbreak in Iquitos, Peru reveals independent origin from a concurrent outbreak in Brazil
Authors: Olortegui Maribel Paredes , Schiaffino Francesca , Peñataro_Yori Pablo , Colston Josh M. , Shapiama_Lopez Valentino , Pinedo_Vasquez Tackeshy , Garcia_Bardales Paul F. , Flynn Thomas G. , Ramal-Asayag Cesar , Hughes Holley R , Davis Emily , Russell Brandy J. , Brault Aaron C. , Palomino Yuri Alfonso Alegre , Munayco Cesar , Liu Jie , Houpt Eric , Cooper Kerry K. , Parker Craig T. , Kosek Margaret N.
Published: December 2024

Oropouche virus is an arbovirus endemic to the Americas. Periodic outbreaks have occurred since its description in 1955. In late 2023, an outbreak occurred in Peru, centered in and around Iquitos in the Eastern Peruvian Amazon. An existing acute febrile illness (AFI) surveillance program was able to document its emergence and characterize arthralgia and dysuria and the absence of diarrhea as distinctive clinical features of Oropouche virus-associated febrile illness relative to other causes of AFI. Sequencing of isolates from the outbreak demonstrated that strains from this region were distinct from those causing disease in Brazil, despite the large-scale movement of people along the Amazon corridor, but highly similar to strains from Colombia and Ecuador. Our findings suggest that the current outbreak in South America is fundamentally multifocal in origin and not the result of geographic spread from Brazil, which experienced an outbreak between 2022 and 2024.
Epidemiological Patterns, Treatment Response, and Metabolic Correlations of Idiopathic Intracranial Hypertension: A US-Based Study From 1990 to 2024
Authors: Azzam Ahmed Y. , Nassar Mahmoud , Morsy Mahmoud M. , Mohamed Adham A. , Wu Jin , Essibayi Muhammed Amir , Altschul David J.
Published: December 2024

Introduction

Idiopathic Intracranial Hypertension (IIH) presents an increasing health burden with changing demographic patterns. We studied nationwide trends in IIH epidemiology, treatment patterns, and associated outcomes using a large-scale database analysis within the United States (US).

Methods:

We performed a retrospective analysis using the TriNetX US Collaborative Network database (1990-2024). We investigated demographic characteristics, time-based trends, geographic distribution, treatment pathways patterns, comorbidity profiles and associated risks with IIH. We used multivariate regression, Cox proportional hazards modeling, and standardized morbidity ratios to assess various outcomes and associations.

Results:

Among 51,526 patients, we found a significant increase in adult IIH incidence from 16.0 to 127.0 per 100,000 (adjusted RR: 6.94, 95% CI: 6.71-7.17). Female predominance increased over time (female-to-male ratio: 3.29, 95% CI: 3.18-3.40). Southern regions showed the highest prevalence (43.0%, n=21,417). Initial medical management success rates varied between acetazolamide (42.3%) and topiramate (28.7%). Advanced interventional procedures showed 82.5% success rates in refractory cases. Cox modeling revealed significant associations between IIH and metabolic syndrome (HR: 2.14, 95% CI: 1.89-2.39) and cardiovascular complications (HR: 1.76, 95% CI: 1.58-1.94), independent of BMI.

Conclusions:

Our findings highlight IIH as a systemic disorder with significant metabolic implications beyond its neurological manifestations. The marked regional disparities and rising incidence rates, especially among adults, suggest the need for targeted healthcare strategies.

Early intervention success strongly predicts favorable outcomes, supporting prompt diagnosis and treatment initiation. These results advocate for an integrated approach combining traditional IIH management with broad metabolic screening care.
Circling back:Vespulaspp. re-invasion after knockout from volcanic ash fall in Patagonia
Authors: Pereira Ana Julia , Corley Juan Carlos , Giménez Gustavo , Masciocchi Maité
Published: December 2024

Effective management of invasive species requires understanding re-invasion dynamics, to prevent control failures, refine methodologies, and enhance protocols. Re-invasion is the process by which eradicated or naturally disappeared exotic species establish themselves again, in previously occupied areas. Re-invasion often bypasses initial invasion phases such as transport and introduction. During re-establishment, changes in the invader, the invaded environment, and species interactions can influence the success of invasion.

We investigated re-invasion patterns ofVespula germanicaandVespula vulgariswasps in NW Patagonia (Argentina) following a significant natural disturbance: the 2011 Puyehue-Cordón Caulle volcanic eruption, which caused unprecedented arthropod defaunation. By establishing 23 sampling sites in heavily affected regions, we conducted sampling events over three years (2012-2014).

Our findings show that re-invasion of bothVespulaspp. occurs fast, with minimal interspecific competition among them observed. The proximity to urban centers, acting as refuges, further facilitated their establishment.

This unique case study highlights the adaptability of these invasive wasps in the face of extreme environmental disruptions. By describing the importance of considering reinvasion routes and refuges, this research may help develop more effective management strategies to controlVespulapopulations.
The effectiveness of Cenobamate in patients previously treated with Vagus Nerve Stimulation for drug resistant epilepsy
Authors: Hogeveen Lara , Legros Benjamin , Meurs Alfred , De Herdt Veerle , Sprengers Mathieu , Hödl Stephanie , Mertens Ann , Gadeyne Stefanie , Raedt Robrecht , Dewaele Frank , Vandersteene Jelle , Boon Paul , Vonck Kristl
Published: December 2024

Background

Vagus Nerve Stimulation (VNS) is an efficacious neuromodulatory treatment for patients with drug resistant epilepsy (DRE). In many VNS treated patients, seizures are not fully controlled. These patients often represent a highly refractory group in whom novel anti-seizure medication (ASM) may be tried. This study evaluates the effectiveness of Cenobamate (CNB) in patients previously treated with VNS.

Methods

The medication history of all patients treated with VNS at Ghent University Hospital and HUB-Hôpital Erasme Brussels between 1995 and 2024 was reviewed. In patients who received an add-on treatment with CNB after at least 12 months of VNS therapy, mean monthly seizure frequency before VNS, after VNS, and after CNB was assessed.

Results

54/620 patients treated with VNS between March 1995 and November 2023 were treated with CNB after a median VNS treatment time of 9 years. With VNS, 13/52 (25%) had a seizure frequency reduction of ≥50%. Side-effects were mild and stimulation-related. After add-on of CNB (median daily dosage of 200mg) for a median follow-up of 10 months, 24/54 (44.4%) became responders. Of these patients, 6 (11.1% from total cohort) reported seizure freedom for a median duration of 26 weeks. Almost half (46.2%) of the VNS non-responders became CNB responder. The median number of concomitant ASM was 3. In 20/54 (37%), the number of ASM was reduced. 7/54 (13%) stopped CNB because of side-effects. Fatigue was the most prevalent side effect in 23/54 patients (42.6%).

Conclusion

In DRE patients treated with VNS therapy who could benefit from further improvement in seizure control, add-on treatment with CNB is useful. This most recently marketed ASM leads to a significant improvement in seizure frequency in more than 40% of the patients.
Genome-wide association study identifies novel risk variants for celiac disease in the 5p15.33 locus: insights from a population-based screening of adults, the HUNT study
Authors: Alam Mohammad Sayeef , Thomas Laurent F. , Brumpton Ben , Hveem Kristian , Lundin Knut E. A. , Withoff Sebo , Jonkers Iris H. , Sollid Ludvig M. , Hjort Rebecka , Ness-Jensen Eivind
Published: December 2024

Previous studies have uncovered genetic loci associated with celiac disease (CeD) within both the human leukocyte antigen (HLA) and non-HLA regions. However, half of the heritability remains unexplained. This study aimed to identify novel loci associated with CeD in a general adult population screened for the disease, mitigating the likely selection bias observed in previous case-control studies. The study utilized data from the fourth Trøndelag Health Study (HUNT4) in Norway, where 52,358 adults were screened for CeD using serology, identifying 465 previously undiagnosed biopsy-confirmed cases. Additionally, 377 previously diagnosed cases were identified through hospital journal searches and registry data. Genotyping of 373,185 single nucleotide polymorphisms was performed on all participant using four Illumina HumanCoreExome arrays. Imputation, using the Haplotype Reference Consortium panel, resulted in approximately 24.9 million variants, post quality control. A genome-wide association study was performed using SAIGE, and functional mapping and pathway enrichment analysis was conducted using FUMA. All except one of the 42 known autosomal loci were present in the data, of which seven reached the suggestive significance threshold (P ≤ 5 × 10−6). Thirteen independent novel associations were observed (P ≤ 5× 10−8), with the 5p15.33 locus showing the highest potential for a true association with CeD, warranting further studies to validate the findings. Notably, theIRX1gene, located close to the 5p15.33 locus has also been associated with rheumatoid arthritis, suggesting a new shared autoimmune locus.
A Machine Learning Framework for Cancer Prognostics: Integrating Temporal and Immune Gene Dynamics via ARIMA-CNN
Authors: Lin Rui-Bin , Zhou Linlin , Lin Yu-Chun , Yu Yu , Yang Hung-Chih , Yu Chen-Wei
Published: December 2024

Hepatocellular carcinoma (HCC) poses a significant global health challenge due to its high incidence and mortality rates. Our study investigates the prognostic significance of chemokine (C-C motif) ligand 5 (CCL5) and various immune gene signatures in HCC using an innovative combination of Autoregressive Integrated Moving Average (ARIMA) and Convolutional Neural Network (CNN) models. Time series data were utilized to apply an ARIMA model that captures the temporal dynamics of CCL5 expression. This model’s residual was integrated with immune signature expression data, including lymphocytes and macrophages, to extract features using a CNN model. Our study demonstrates that CNN-extracted features yield a statistically more robust association with patient survival compared to the traditional median split method, which primarily focuses on single-gene analysis. Specifically, CNN-extracted features from CD8 T cells and effector T cells resulted in a hazard ratio (HR) of 0.7324 (p= 0.0008) with log-rankp-value (0.0131), underscoring their pivotal role in the anti-tumor immune response. This methodology highlights the superior prognostic value obtained through integrated multi-gene analyses, providing deeper insights into tumor-immune interactions than conventional single-gene approaches. Moreover, clustering immune genes based on non-parametric correlations unveiled distinct survival patterns. A cluster comprising B cells, Th2 cells, T cells, and NK cells exhibited a moderate protective effect (HR: 0.8714,p= 0.1093) alongside a significant log-rankp-value (0.0233). However, the cluster, including granulocytes, Tregs, macrophages, and myeloid-derived suppressor cells, showed no significant survival association, highlighting the intricate immune regulation within the tumor microenvironment. These findings emphasize the necessity of incorporating temporal dynamics and synergistic immune gene interactions for more accurate prognostic evaluations. Our integrated ARIMA-CNN framework represents a significant advancement, leveraging both linear and nonlinear modeling to uncover the dynamic influence of multiple immune genes. This framework holds excellent potential for identifying robust biomarkers and personalizing immunotherapy strategies, ultimately paving the way for innovative cancer management solutions.
Genetic Architecture of Postpartum Psychosis: From Common to Rare Genetic Variation
Authors: Jung Seulgi , Caballero Madison , Kępińska Adrianna , Smout Shelby , Munk-Olsen Trine , Robakis Thalia K. , Bergink Veerle , Mahjani Behrang
Published: December 2024

Postpartum psychosis is a severe psychiatric condition marked by the abrupt onset of psychosis, mania, or psychotic depression following childbirth. Despite evidence for a strong genetic basis, the roles of common and rare genetic variation remain poorly understood. Leveraging data from Swedish national registers and genomic data from the All of Us Research Program, we estimated family-based heritability at 55% and WGS-based heritability at 37%, with an overrepresentation on the X chromosome. Rare coding variant analysis identifiedDNMT1andHMGCRas potential risk genes (q < 0.1). Analysis of 240,009 samples from All of Us demonstrated significant associations between these genes and multiple psychiatric disorders, supporting their biological relevance. Additionally, 17% of bipolar disorder, 21% of schizophrenia, and 16–25% of multiple autoimmune disorder risk genes overlapped with postpartum psychosis. These findings reveal unique genetic contributions and shared pathways, providing a foundation for understanding pathophysiology and advancing therapeutic strategies.
Diverging repeatomes in holoparasitic Hydnoraceae uncover a playground of genome evolution
Authors: Kim Woorin , Schmidt Nicola , Jost Matthias , Mkala Elijah Mbandi , Winkler Sylke , Hu Guang-Wan , Heitkam Tony , Wanke Stefan
Published: December 2024

The nuclear genomes of parasitic plants have undergone unique evolutionary trajectories to adapt to the heterotrophic lifestyle. These adaptations often involve large genomic alterations, potentially driven by repetitive DNAs. Despite the recognized role of repetitive DNAs for shaping plant genomes, their contribution to parasitic plant genome evolution remains largely unexplored. This study presents the first analysis of repetitive DNAs in eleven genomes of Hydnoraceae, a holoparasitic plant family.

The repetitive DNAs were identified and annotatedde novo. Patterns of abundance and presence-absence were aligned with the phylogenetic relationships, geographical distribution, and host shifts, suggesting repetitive DNAs’ key role in shaping Hydnoraceae genomes.

The two Hydnoraceae genera,HydnoraandProsopanche, exhibit distinct profiles. EightHydnoragenomes are largely populated by long terminal repeat retrotransposons, while threeProsopanchegenomes vary greatly in repetitive DNA composition, includingP. bonacinaewith massive amplifications of a single DNA transposon andP. panguanensiswith over 15% 5S rDNA, compared to <0.1% in some Hydnoraceae. Both extremely low and very high abundance of 5S rDNA challenges our current understanding on chromosomal stabilization and rDNA transcription.

These genome dynamics, while inviting for further investigations, suggest rapidly evolving repeat profiles, potentially accelerated by the adaptation to the parasitic lifestyle.
A bacterial site 2 protease contributes to RNA phage resistance by targeting phage lysis protein
Authors: Bae Hee-Won , Kim So-Youn , Choi Shin-Yae , Ki Hyeong-Jun , Ahn Se-Jeong , Cho You-Hee
Published: December 2024

Lytic phages culminate their lifecycle by causing lysis of the infected host cell. Despite extensive research on the molecular mechanisms of phage lysis, our understanding of anti-phage resistance mechanisms during the lysis stage remains less understood. Here, we demonstrated that MucP, a site 2 protease ofPseudomonas aeruginosa(PA), mitigates the activity of the RNA phage PP7 lysis protein (LP), which contains a transmembrane (TM) helix, suggesting that MucP act as a resistance mechanism against PP7-induced lysis. We identified an LP variant (LP*) having enhanced helical propensity due to P26L and S40L mutations, which was unaffected by MucP and exhibited killing activity against PA strains that are resistant to the wild type LP, with an inverse correlation between MucP activity and LP susceptibility. A PP7 mutant with LP* exhibited MucP-escaper phenotype such as discernable plaque formation on MucP-expressing cells. These results suggest that MucP targets the RNA phage LP at the TM helix in certain strains, providing a resistance function compromising phage lysis by utilizing an existing bacterial enzyme in PA.

SIGNIFICANCE

Host cell lysis is the last step of the phage lifecycle, occurring only when the progeny virions reach a certain number. The factors influencing coordinated lysis have not been well-studied, particularly in the context of the evolutionary arms race between phages and their hosts. Our study identifies MucP, a membrane protease inPseudomonas aeruginosa(PA), as a resistance mechanism against the RNA phage PP7 by destabilizing its lysis protein (LP), which has lower helical tendency at the transmembrane (TM) domain. An LP variant with higher helical tendency exhibits strong killing activity against PA strains normally resistant to LP-mediated killing, revealing an inverse correlation between MucP activity and LP susceptibility in various PA clinical stains. Given that MucP is a conserved protease critical for mucoid conversion in PA, we propose that MucP offers a phage resistance mechanism or an intrinsic or nonprofessional defense mechanism against the RNA phages, which varies among the phenotypically diverse PA isolates.

SYNOPSIS

Pseudomonas aeruginosaMucP, a site 2 protease, destabilizes the PP7 lysis protein (LP).

Helical propensity of the LP transmembrane domain affects MucP-susceptibility.

Clinical strains with higher MucP activity exhibit greater LP and RNA phage resistance.

PP7* with MucP-resistant LP* shows broadened spectrum with no less reduced infectivity.

Abstract Figure
Structural Determinants of Mucins in Influenza Virus Inhibition: The Synergistic Role of Sialylated Glycans and Molecular Size
Authors: Butnarasu Cosmin , Safferthal Marc , Thomas Jolly , Povolotsky Tatyana L. , Diehn Robyn , Fentker Kerstin , Mertins Philipp , Pagel Kevin , Lauster Daniel
Published: December 2024

Mucins are heavily glycosylated proteins that play a crucial role in protecting mucosal surfaces against pathogens, including influenza viruses. This study investigates the antiviral properties of bovine submaxillary mucins (BSM) as a model for oral mucins against the influenza virus (A/H3N2 subtype), focusing on glycan composition and mucin size. BSM was purified, and characterized by proteomic and glycomic analysis and its antiviral efficacy was assessed after selective removal of sialic acids,N-glycans, or all glycans via enzymatic and chemical treatments. We employed virus binding and inhibition assays, including microscale thermophoresis (MST) and hemagglutination inhibition (HAI), to characterize processed mucins for structure activity correlations. Removal of sialic acids reduced BSM’s antiviral activity by over 10-fold, while complete glycan removal abolished it entirely, highlighting sialylatedO-glycans as critical for viral inhibition.N-glycan removal had minimal impact on antiviral efficacy. A size-dependent antiviral effect was observed: smaller mucin fragments (∼50 and 330 kDa), which retained comparableO-glycosylation patterns, showed significantly reduced inhibition and viral binding affinity compared to intact BSM. These findings underscore the importance of mucin size and sialylatedO-glycans in antiviral defense mechanisms against influenza.

Significance

This study sheds light on the intrinsic antiviral properties of mucin from the bovine submaxillary gland, revealing the roles of glycans and mucin’s size in binding and inhibiting influenza virus. Our findings suggest a clear correlation between sialylatedO-glycans and mucin size with the antiviral efficacy. Ultimately, we show that mucin-derived fragments retaining virus-binding capacity, with defined size andO-glycosylation patterns, can be isolated from mucin and could serve as versatile building blocks for designing next-generation antiviral biomaterials.
Evidence for the pairing of mRNA exiting ribosomes acting as a Driver of unidirectional forward bypassing: Its cessation permits Backwards scanning
Authors: Wills Norma M. , Parsawar Krishna , Atkins John F.
Published: December 2024

Efficient translational avoidance of a 50 nucleotide non-coding insert in phage T4 gene60sequence involves dissociation of peptidyl-tRNA pairing from the mRNA ‘take-off’ codon, GGA. This tRNA is retained in the ribosomal P-site during bypassing. Its anticodon does not scan the 5’ part of the non-coding sequence, which contains a cognate GGG codon, but it does scan the main and 3’ part of the coding gap for potential complementarity. Re-pairing to a matched GGA ‘landing site’ codon occurs exclusively 48-50 nt after take-off. Coding resumption ensues. Here we analyze proteins synthesized from mutants that abrogate the potential for re-pairing at the canonical landing site. The results show that some ribosomes move backwards 39 nt allowing re-pairing to the initially hidden GGG or forwards at least 56 additional nt before resumed anticodon: codon pairing at a downstream matched codon. We discuss the nature of the driving force for the initial unidirectional movement and why it becomes dissipated when the site of landing in WT is reached. Also presented is an analysis of the relative importance of recoding signals located 6 nucleotides upstream (5’) and close downstream (3’) of the WT landing site, for re-pairing to mRNA and coding resumption.