bluuebunny/crossref_metadata_2025 huggingface dataset:
SLE Partition Functions via Conformal Welding of Random Surfaces
Authors: Sun Xin , Yu Pu
Published: November 2024

Schramm–Loewner evolution (SLE) curves describe the scaling limit of interfaces from many 2D lattice models. Heuristically speaking, the SLE partition function is the continuum counterpart of the partition function of the corresponding discrete model. It is well known that conformally welding of Liouville quantum gravity (LQG) surfaces gives SLE curves as the interfaces. In this paper, we demonstrate in several settings how the SLE partition function arises from conformal welding of LQG surfaces. The common theme is that we conformally weld a collection of canonical LQG surfaces which produces a topological configuration with a random conformal structure. Conditioning on the conformal modulus, the surface after welding is described by Liouville conformal field theory, and the density of the random modulus contains the SLE partition function for the interfaces as a multiplicative factor. The settings we treat includes the multiple SLE for $\kappa \in (0,4)$, the flow lines of imaginary geometry on the disk with boundary marked points, and the boundary Green function. These results demonstrate an alternative approach to construct and study the SLE partition function, which complements the traditional method based on stochastic calculus and differential equation.
Control of iron acquisition by multiple small RNAs unravels a new role for transcriptional terminator loops in gene regulation
Authors: Solchaga Flores Eugenio , Jagodnik Jonathan , Quenette Fanny , Korepanov Alexey , Guillier Maude
Published: November 2024

Small RNAs (sRNAs) controlling gene expression by imperfect base-pairing with mRNA(s) are widespread in bacteria. They regulate multiple genes, including genes involved in iron homeostasis, through a wide variety of mechanisms. We previously showed that OmrA and OmrB sRNAs repress the synthesis of the Escherichia coli FepA receptor for iron–enterobactin complexes. We now report that five additional sRNAs, namely RprA, RybB, ArrS, RseX and SdsR, responding to different environmental cues, also repress fepA, independently of one another. While RprA follows the canonical mechanism of pairing with the translation initiation region, repression by ArrS or RseX requires a secondary structure far upstream within the long fepA 5′ untranslated region. We also demonstrate a dual action of SdsR, whose 5′-part pairs with the fepA translation initiation region while its 3′-end behaves like ArrS or RseX. Strikingly, mutation analysis shows a key role for the loops of these sRNAs’ intrinsic terminators in the regulation. Furthermore, regulation depends on both the Hfq chaperone and the RNase E endonuclease. Overall, our data strongly suggest that FepA levels must be tightly controlled under a variety of conditions and highlight the diversity of mechanisms that underly the regulation of gene expression by sRNAs in bacteria.
Challenges and opportunities in 2D materials for high-performance aqueous ammonium ion batteries
Authors: Xu Jie , Liu Tao , Dong Xusheng , Dong Xiaoyi , Zhou Wanhai , Li Xiaojie , Chao Dongliang , Zhou Zhen , Zhao Ruizheng
Published: November 2024

Aqueous ammonium ion batteries (AAIBs) have attracted considerable attention due to their high safety and rapid diffusion kinetics. Unlike spherical metal ions, NH4+ forms hydrogen bonds with host materials, leading to a unique storage mechanism. A variety of electrode materials have been proposed for AAIBs, but their performance often falls short in terms of future energy storage needs. Hence, there is a critical need to design and develop advanced electrode materials for AAIBs. 2D materials, with their tunable interlayer spacing, remarkable interfacial chemistry and abundant surface functional groups, are an ideal choice for electrode materials for NH4+ storage. This review highlights the latest research on 2D electrode materials for AAIBs, providing insights into their working principles, NH4+ storage mechanisms and control strategies for designing high-performance AAIBs. Furthermore, a summary and future perspectives on 2D electrode materials in the development of AAIBs are provided, aiming to promote the advancement of high-performance AAIBs.
Ecological drivers of coloniality in Oreotrochilus chimborazo chimborazo (Chimborazo Hillstar), a hummingbird endemic to the High Andes of Ecuador
Authors: Cañas-Valle Gustavo X , Bouzat Juan L
Published: November 2024

The adaptive significance of group-living has promoted considerable debate about the potential role of environmental drivers in the evolution of coloniality. Nest aggregations may result as a plastic response of reproductive individuals to limited substrate availability and favorable environmental conditions for nesting (limited substrate availability hypothesis). However, few studies have demonstrated the direct role of environmental factors in promoting social aggregations. A population survey of Oreotrochilus chimborazo chimborazo (Chimborazo Hillstar), a hummingbird subspecies endemic to the Ecuadorian High Andes, resulted in the identification of 7 nesting aggregations and 13 solitary nests. Of a total of 74 active nests detected, most (82%) were found in reproductive colonies. Furthermore, nesting aggregations were consistently associated year-round with roosting groups of males and non-reproductive females, a unique case among birds. These findings challenge the widespread assumption that hummingbirds are highly competitive solitary nesters. The subsequent characterization of O. c. chimborazo nesting habitat revealed that wind speed, temperature, humidity, and landscape features associated with substrate availability, ground cover vegetation, and water represent environmental factors associated with nesting, consistent with the limited substrate availability hypothesis. However, a semi-natural “experiment” comparing occupancy of solitary nesting locations vs. nesting aggregations revealed that only 45.5% of the sites available for solitary nesting showed individual active nests, significantly lower than the 95% expected by random simulations. In contrast, nesting aggregations consistently had multiple active nests at significantly higher frequencies than expected, producing broods across multiple reproductive seasons. These results suggest that other factors beyond those associated with the limited substrate availability hypothesis may play a role in the development of nesting/roosting aggregations in O. c. chimborazo, emphasizing the importance of the interaction of environmental and social factors in driving coloniality in birds.
Ships, Guns and Money: The Logistics of Revolution and Garibaldi’s Campaign of 1860
Authors: Banks Daniel F
Published: November 2024

When Giuseppe Garibaldi set sail for Sicily on the campaign that led to the unification of Italy in 1860, he gave a group of exiled political radicals living in the port city of Genoa the task of procuring weapons, equipment and reinforcements for his expedition. These exiled veterans of the 1848 revolutions quickly developed a fluid yet highly integrated fundraising and procurement organization that provided Garibaldi with the means for success. To do this, they leveraged decades of experience as clandestine transnational organizers, but also relied on the business and professional expertise and contacts they had accrued during a commercial and industrial boom in Genoa in the 1850s. Crucially, they took advantage of logistical innovations like steam travel to concentrate people and equipment where and when they needed them and guarantee a positive outcome for their revolution. They also successfully negotiated with trans-imperial power brokers and navigated jurisdictional gaps in the waters of the Mediterranean. These former 48ers used their experiences as exiles and businessmen to challenge the conservative status quo of the 1850s and force the creation of a united Italy. A focus on the material underpinning of their success restores their role in transforming nineteenth-century Europe.
National Study Examining Excellence and Value in Physical Therapist Residency Education: Part 2—A Call to Action
Authors: Osborne Raine , Briggs Matthew S , Kraft Sara , Rapport Mary Jane , Black Lisa , Tichenor Carol Jo , Hartley Gregory W , Bailey Chloe E , Jensen Gail M
Published: November 2024

This Perspective provides a crucial set of actions with corresponding recommendations aimed at propelling the physical therapy profession toward excellence in residency education. The conceptual model includes elements of excellence in the delivery and outcomes of physical therapist residency education and the domain of value experienced by stakeholders impacted by physical therapist residency education. Linked to the conceptual model, the 15 actions, and 28 recommendations draw from (1) the Physical Therapist Residency Excellence and Value (PT-REV) study, (2) the Physical Therapist Education for the 21st Century (PTE-21) study, and (3) research in the learning sciences. This paper proposes a transformative call for decisive and consistent reform directed toward residency programs, residents, sponsoring organizations, and the physical therapy profession. Physical therapist residency education, initiated over 23 years ago, is no longer in its infancy with critical gaps in its maturation that need to be addressed systematically by stakeholders across the profession, thus improving the profession’s ability to respond to changing societal needs.

This Perspective serves as a call to action and provides specific recommendation for what is needed to promote and achieve excellence in physical therapist residency education to improve the professions’ ability to adapt to changing societal needs.
Transcriptional and functional regulation of cell cycle and UV response by PPARβ in human skin epidermal cells
Authors: Nguyen Thanh Nhan , Winkler Carine , Ginster Stefanie , Claudinot Stéphanie , Michalik Liliane , Jafari Paris
Published: December 2024

Solar radiation is the main source of human exposure to UV rays, which is the major carcinogen in skin cancers by inducing DNA damage. Skin cells repair these damages by activating the DNA damage response (DDR) to safeguard genome integrity, thereby preventing skin cancers. Peroxisome proliferator‐activated receptor beta (PPARβ), a druggable transcription factor, is involved in the development of UV‐dependent skin cancers, although its role is not mechanistically elucidated. We showed previously that PPARβ knockout (KO) mice are less prone to UV‐induced skin cancers. Here, we report that PPARβ directly regulates gene expression programs associated with cell cycle and DNA repair pathways in normal human epidermal keratinocytes (NHEK). The loss of function of PPARβ in human keratinocytes led to a downregulation in the expression of key cell cycle regulators, including cyclins and cyclin‐dependent kinases (CDKs). Simultaneously, it upregulated the expression of p21 protein, a known CDK inhibitor. These molecular alterations resulted in a significant reduction in cell proliferation and induced cell cycle arrest at the G2/M phase. Moreover, the absence of functional PPARβ disrupted the expression and activation of the ataxia telangiectasia and Rad3‐related (ATR) pathway, a critical component of the cellular response to UV‐induced DNA damage. The alterations in the ATR pathway likely contributed to an increased apoptotic response of NHEK to UV radiation. Using a mouse melanoma model, we demonstrated that the depletion of PPARβ decreases tumorigenicity of melanoma cells and delays tumor formation. Our data suggest that PPARβ inhibition could be considered as a therapeutic target for the prevention of UV‐induced skin cancers, by regulating cell proliferation, attenuating DDR, and eliminating skin cells with high UV‐induced mutational burden.
Treatment of relapse valgus knee deformity in fibular hemimelia with hemiepiphysiodesis
Authors: Cuoghi Ana Gabriela Santana , Paccola Ana Maria Ferreira , Pagotto Roger Frossard , Prina Douglas Manuel Carrapeiro , Nogueira Monica Paschoal
Published: November 2024

The objective of this study was to analyze the treatment of recurrent valgus knee in fibular hemimelia patients with hemiepiphysiodesis and define associated variables for deformity relapse. Sixteen consecutive patients with fibular hemimelia treated with hemiepiphysiodesis (57 physis) were compared to 21 physis of idiopathic cases, in terms of magnitude, speed, and time of correction. Correction of valgus deformity was successfully achieved in all cases. In the fibular hemimelia group, children 4 years and younger had a bigger magnitude of correction than older ones (11° versus 6.9°) and greater speed (1° versus 0.6°), with statistical significance (P = 0.018 and P = 0.009, respectively), while time for correction was similar among these groups (11.6 months versus 12.3 months). Femoral distal physis corrected faster than proximal tibial physis (10.8 months versus 16.8 months), with statistical significance (P = 0.032). Thirty-three physis (57.9%) were isolated and 24 (42.1%) were tibia and femur. We found no statistical difference between the two groups regarding time for correction, magnitude, or speed (P = 0.526, P = 0.910, P = 0.803, respectively). Relapse was observed in 49 physis (86%) of the fibular hemimelia patients. These had a mean age of 5.5 years versus 3.9 years for those without a relapse, with statistical significance (P = 0.204). Relapse occurred after 2 years of the first procedure. Recurrent valgus deformity in fibular hemimelia can be successfully treated with single or multiple hemiepiphysiodesis with tension band plates in skeletally immature patients in an effective and gradual manner. Level of Evidence: Level III, therapeutic study.
Unrecognized Provider Burden During Hospital EMR Introduction
Authors: Poelstra Kornelis , Cooper Lara
Published: December 2024

Introduction:

The introduction of—or the transition to—a new electronic health record system (EHR) places an unrecognized burden on health care providers in our ever-changing health care environment of increased mandates, increased overhead, and reduced reimbursement to practice medicine.

Purpose:

The purpose of this study was to track the non-reimbursed time investment required for 6 providers from an independent spine surgery practice after a hospital system independently decided to transition to a new EHR system.

Results:

Between the 6 providers of the practice, 266 hours of required classroom time, in-person training, and video and phone call teaching sessions had to be completed to become “proficient” so that clinical utilization of the system for in-patient care was certified by the hospital trainers and the EHR company.

Conclusions:

The burdens associated with the introduction of mandatory EHRs are putting tremendous pressure on providers from a time commitment perspective. This detracts from patient care during that time and deserves to be compensated for by the EHR companies that extract billions of dollars from both federal and private insurers’ health care budgets.
Geospatial Mapping of Head and Neck Cancer Research
Authors: Glehan Alexander , Kumaresan Talitha , Ramsey Tam , Kumaresan Jonathan , Gildener-Leapman Neil
Published: November 2024

Objective:

To report geographic distribution and characteristics of head and neck cancer (HNC) clinical trials in the United States.

Methods:

We conducted a retrospective analysis of U.S. HNC clinical trials searching ClinicalTrials.gov from January 1, 2017 to December 31, 2021 using the terms “head and neck cancer” or “head and neck neoplasms.”

Results:

A total of 381 clinical trials met inclusion criteria with 2181 trial opportunities, which were correlated with population density. Of the U.S. population, 72% live within a 25-mile radius of trials. California, Pennsylvania, and New York had the greatest number of clinical trial entries. The majority of patients living more than 25 miles from an HNC clinical trial site are located in rural areas. One hundred sixty-five (43.3%) trials were about systemic therapy, of which 138 (83.6%) involved targeted immunotherapy. There were 286 unique principal investigators. One hundred six (37.1%) were females and 180 (62.9%) were males.

Conclusions:

We demonstrate disparity in the geographic distribution of HNC trials favoring densely populated urban areas, which may limit patient access due to travel burden. Studies are skewed towards immunotherapy drug trials, with fewer radiation and surgery investigations.

Level of Evidence:

Level III.
Artificial Intelligence and Postpartum Hemorrhage
Authors: Mathewlynn Sam J , Soltaninejad Mohammadreza , Collins Sally L
Published: December 2024

Postpartum hemorrhage (PPH) remains a significant contributor to maternal mortality and morbidity worldwide, with approximately 14 million women affected annually and 70,000 resulting deaths. Despite advances in health care, PPH continues to pose challenges even in developed settings. Apart from mortality, PPH leads to various adverse outcomes and morbidity. Recently, there has been a surge in interest in using artificial intelligence (AI), including machine learning and deep learning, across many areas of health care. This article explores the application of AI in tackling PPH, including predictive modeling and risk stratification. Some studies have shown promising results in predicting PPH. However, external validation of these models is crucial and frequently lacking, with barriers including differences in cohort characteristics and variations in outcome measurement methods. Most of the existing research has taken place in well-resourced health care settings, and there is a lack of models applicable to resource-limited settings where the need is arguably greatest. Incorporating uterine contractility metrics and radiomics into predictive models offers new avenues for enhancing prediction accuracy. Beyond risk prediction, AI has also been explored in other aspects of PPH management, including blood product management and early detection using wearable devices. In conclusion, while AI presents exciting opportunities for PPH prediction and management, challenges such as model validation, clinical translation, and applicability in diverse health care settings remain. Further research, particularly in low-and middle-income countries, is necessary to realize the full potential of AI for addressing the global burden of PPH.
Persistent Genital Arousal Disorder/Genitopelvic Dysesthesia
Authors: Pukall Caroline F.
Published: December 2024

Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is a distressing condition characterized by persistent or recurrent, unwanted, or intrusive sensations of genital arousal that occur in the absence of subjective feelings of sexual desire that persist for at least 3 months. Despite its negative psychosocial impact, including high levels of suicidal ideation, it is not well known by most health care providers and can easily be misdiagnosed or remain undiagnosed. This paper describes a detailed biopsychosocial regional algorithm for the assessment and management of PGAD/GPD and draws attention to the need for multidisciplinary approaches to its effective management.
Cardiac selectivity in pulsed field ablation
Authors: Meng Fanchao , Jin Shuqi , Liu Nian
Published: November 2024

Purpose of review

This review examines the selective cardiac injury induced by pulsed electric fields during atrial fibrillation ablation. It consolidates findings from both preclinical and clinical studies on cardiac selectivity and explores the potential mechanisms behind this selectivity.

Recent findings

Preclinical studies indicate that pulsed electric fields cause significantly more myocardial injury compared with other tissues. Clinical studies have similarly shown that complication rates for pulsed field ablation are notably lower than those for radiofrequency and cryoballoon ablation.

Pulsed field ablation demonstrates a notable selectivity for myocardial injury, likely because of the unique functional and metabolic characteristics of cardiomyocytes. This review delves into the underlying principles of cardiac selectivity and proposes future directions for improving this selectivity. It is important to note that while pulsed field ablation shows promise, its cardiac selectivity is not absolute, as some complications still occur, necessitating further research.
Metabolic issues in patients with metabolic dysfunction–associated steatohepatitis (MASH) and their impact on MASH recurrence following liver transplantation: A narrative review
Authors: Alnimer Lynna , Arellano Diego , Brombosz Elizabeth , Noureddin Mazen
Published: December 2024

Decompensated cirrhosis secondary to metabolic dysfunction–associated steatohepatitis (MASH) is not only a common indication for liver transplant (LT) but is becoming the leading cause of LT in postmenopausal women in the United States. Given the different complex mechanisms involved in the occurrence of MASH, it is being recognized as the hepatic manifestation of the metabolic syndrome. There are multiple metabolic issues associated with MASH, including obesity, DMT2, cardiovascular disease, and chronic kidney disease, which need to be addressed in the pretransplant and posttransplant setting for better patient outcomes. Recurrence of MASH following LT can occur due to many reasons including reversal of the catabolic state seen in cirrhosis, improvement in appetite, and the effect of certain post-LT medications on the graft; however, managing recurrence can be challenging and thus urges addressing these issues before transplant, in addition to recognizing, and treating them in the posttransplant setting. In this review, we discuss the various metabolic issues that face patients with MASH and the medical and surgical management options available to improve outcomes and reduce chances of recurrence.
Optical coherence tomography versus angiography to guide percutaneous coronary intervention in patients with in-stent restenosis: an observational study
Authors: Wang Yi-Fei , Xu Tian , Meng Pei-Na , You Wei , Xu Yi , Kong Xiao-Han , Wu Xiang-Qi , Wu Zhi-Ming , Zhao Meng-Yao , Jia Hai-Bo , Wang Feng , Ye Fei
Published: December 2024

Background

Although optical coherence tomography (OCT) guidance with the ‘MLDMAX’ criteria is very useful for de-novo lesions during percutaneous coronary intervention (PCI), there are limited studies on its benefits in patients with in-stent restenosis (ISR). This study aimed to compare the clinical outcomes of patients with ISR who underwent repeat PCI (re-PCI) with OCT or angiographic guidance.

Methods

This retrospective study enrolled 2142 patients with ISR who underwent re-PCI at Nanjing First Hospital from January 2016 to January 2023. The primary endpoint was the incidence of target vessel failure (TVF) post-re-PCI within 3 years. The secondary endpoints included each component of TVF.

Results

After propensity score matching, 161 matched pairs were enrolled. OCT guidance of re-PCI was associated with a significantly lower risk of TVF compared with angiographic guidance alone [hazard ratio (HR), 0.51; 95% confidence interval (CI), 0.31–0.83; P = 0.007] in patients with ISR. However, only 68.9% of patients with ISR met the final criteria of ‘MLDMAX’ post-re-PCI, which was associated with a lower risk of TVF compared with patients without meeting the OCT criteria (HR, 0.24; 95% CI, 0.11–0.54; P < 0.001), and satisfied the angiographic criteria (HR, 0.40; 95% CI, 0.19–0.85; P = 0.017).

Conclusion

Compared with angiographic guidance, OCT guidance significantly reduced TVF risk following re-PCI for ISR lesions, especially for patients who met the final criteria of ‘MLDMAX’.
Antioxidants and the risk of metabolic dysfunction-associated steatotic liver disease: results of National Health and Nutrition Examination Survey and two-sample Mendelian randomization analyses
Authors: He Yijia , Ye Miaomin , Xia Yin , Zhong Ziyi , Li Qian
Published: December 2024

Background

The link between antioxidants and metabolic dysfunction-associated steatotic liver disease (MASLD) is a topic of considerable discussion in the field of observational studies, with the exact causal connections still being unclear.

Methods

In this investigation, a cohort consisting of 17 061 participants from the National Health and Nutrition Examination Surveys was studied. Initially, a cross-sectional analysis was carried out to examine the relationship between the CDAI and MASLD. Further, Mendelian randomization (MR) was utilized to assess the possible causal links between antioxidant levels in the bloodstream and MASLD.

Results

The association between the CDAI and MASLD was found to be significant in the fully adjusted logistic regression model, showing an OR of 0.95 [95% confidence interval (CI): 0.94–0.97; P < 0.001]. The use of restricted cubic spline regression revealed no significant nonlinear association between the CDAI and the occurrence of MASLD (P
nonlinearity = 0.321). Additionally, MR findings did not suggest any causal connections between circulating levels of various antioxidants and MASLD. These antioxidants included vitamin A (retinol) (IVW: OR: 0.67, 95% CI: 0.33–1.36, P = 0.272), vitamin C (ascorbate) (IVW: OR: 0.61, 95% CI: 0.34–1.09, P = 0.094), vitamin E (α-tocopherol) (IVW: OR: 0.55, 95% CI: 0.13–2.25, P = 0.407), vitamin E (γ-tocopherol) (IVW: OR: 0.89, 95% CI: 0.36–2.23, P = 0.806), zinc (IVW: OR: 0.95, 95% CI: 0.82–1.09, P = 0.449), selenium (IVW: OR: 0.98, 95% CI: 0.84–1.16, P = 0.855), and carotene (IVW: OR: 0.80, 95% CI: 0.36–1.81, P = 0.596).

Conclusion

The findings highlight a significant negative linear relationship between CDAI and MASLD prevalence in the observational component of the study. However, the MR analysis did not indicate any causal effects of circulating antioxidant levels on MASLD.
Social Perceptions of Preoperative and Postoperative Photographs of Patients With Syndromic Craniosynostosis Undergoing Le Fort III Advancement
Authors: Swift Clarice A. , Morin Samantha D. , Benedict Katherine C. , Bhanat Eldrin L. , Humphries Laura S. , Hoppe Ian C.
Published: December 2024

In patients with syndromic craniosynostosis and midface hypoplasia, the Le Fort III osteotomy is a surgical intervention that alleviates nasopharyngeal obstruction and improves facial features that influence societal perceptions of a patient’s attractiveness and interpersonal characteristics. This study determines how perceptions of personality traits, expressed emotion, interpersonal experiences, and expected life achievements and experiences changed in pediatric patients with syndromic craniosynostosis and midface hypoplasia undergoing Le Fort III osteotomy with distraction osteogenesis. The goal of this study is to help quantify the significance of surgical interventions on these perceived social parameters to guide preoperative education and manage expectations with patients and their families.
Sensitivity of M2tidal magnetic signals to seasonal and spatial variations of ocean electric conductivity
Authors: Velímský J. , Šachl L.
Published: December 2024

Electrical conductivity of the Earth’s oceans is an important oceanographic parameter related through its dependence on temperature and salinity to the state of the ocean. The tidally induced magnetic field then provides a directly and globally observable physical variable affected by the ocean conductivity spatial and temporal distribution. This contribution addresses two topics of the impact of the ocean conductivity variations on the principal lunar semi-diurnal magnetic signals. First, using high-resolution forward modelling, we investigate the sensitivity of the magnetic field to seasonal conductivity variations. Here, we find that the differences between magnetic signatures calculated for individual monthly conductivity climatologies are small, and localized to the marginal seas of the global ocean. Second, we formulate an inverse method to provide a constraint for the ocean conductivity in the upper 1000 m of the ocean, and test it using a synthetic dataset, demonstrating a proof-of-concept for such an approach.

This article is part of the theme issue ‘Magnetometric remote sensing of Earth and planetary oceans’.
Molecular characterization of enteroviruses circulating among pigs and goats in two Central African countries, Cameroon and the Central African Republic.
Authors: MODIYINJI Abdou Fatawou , JOFFRET Marie-Line , NOMBOT-YAZENGUET Marina Prisca de Marguerite , ENDENGUE ZANGA Marie-Claire , SADEUH-MBA Serge , NJOUOM Richard , Bessaud Mael
Published: December 2024

To date, data on animal enteroviruses (EVs) are scarce, especially in Central Africa. The aim of this study was to characterize EVs among pigs and goats in Cameroon and Central African Republic. A total of 226 pig and goat faecal samples collected in two previous studies carried out in Cameroon and CAR were pooled and were screened with molecular assays targeting EV-Es, EV-Fs and EV-Gs. EV genomes were amplified by RT-PCR and their sequences obtained by Illumina sequencing and de novo assembly. Based on the capsid sequences, 27 EV-G sequences were identified and assigned to 11 virus types while no EV-E or EV-F was observed. Phylogenetic analysis revealed that the EV-Gs detected in Central Africa do not form specific cluster compared to EV-Gs previously reported in other continents. This suggests a worldwide circulation of EV-Gs, which is likely due the massive international trade of live animals. One human EV, EVC-99, which belongs to the species Enterovirus C, was detected in pigs. This is the third detection of such an event in a similar context, reinforcing the hypothesis that some EV-Cs could be infecting pigs. Our work provides new data on the genetic diversity of EVs circulating among domestic animals in Central Africa.
Transformer-based long-term predictor of subthalamic beta activity in Parkinson’s disease
Authors: Falciglia Salvatore , Caffi Laura , Baiata Claudio , Palmisano Chiara , Isaias Ioannis Ugo , Mazzoni Alberto
Published: November 2024

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a mainstay treatment for patients with Parkinson’s disease (PD). The adaptive DBS approach (aDBS) modulates stimulation, based on the power in the beta range ([12 30] Hz) of STN local field potential, aiming to follow the patient’s clinical state. Control of aDBS relies on identifying the correct thresholds of pathological beta power. Currently, in-person reprogramming sessions, due to changes in beta power distribution over time, are needed to ensure clinical efficacy. Here we present LAURA, a Transformer-based framework predicting the nonlinear evolution of subthalamic beta power up to six days in advance, based on the analysis of chronic recordings. High prediction accuracy (>90%) was achieved in four PD patients with chronic DBS over months of recordings, independently from stimulation parameters. Our study paves the way for remote monitoring strategies and the implementation of new algorithm for personalized auto-tuning aDBS devices.
A-tDCS over DLPFC is no more effective than placebo in improving cognition and pain-experience in chronic lower back pain
Authors: Corti Emily J. , Marinovic Welber , Nguyen An T. , Gasson Natalie , Loftus Andrea M.
Published: November 2024

Chronic pain is associated with deficits in cognitive functioning and increased pain intensity. Research investigating the potential for transcranial direct current stimulation (tDCS) to improve cognitive functioning, pain experience, and psychological health in individuals with chronic lower back pain (CLBP) yield mixed results. The present randomised, placebo-controlled study examined the impact of anodal-tDCS over left-dorsolateral prefrontal cortex (left-DLPFC) on cognitive functioning, pain experience, and psychological health in those with CLBP. Thirty participants with CLBP (Mage = 57.47 years, SDage = 14.28 years) received 20-minutes of sham or anodal tDCS, twice weekly, for 4 weeks. Cognitive functioning was assessed using two measures for each of the five cognitive domains; memory, attention and working memory, executive function, visuospatial, and language. Cognition, pain experience, and psychological health were assessed prior to and immediately following the tDCS intervention. Linear Mixed Models revealed a significant tDCS group and time interaction on an attention and working memory task, whereby participants in the a-tDCS showed a significant improvement on the letter number sequencing task at post-intervention. There was a significant main effect of time for both tDCS groups across the five cognitive domains. Both groups demonstrated a significant improvement on at least one measure for each of the five cognitive domains. Linear Mixed Models revealed there was a significant main effect of time for both tDCS groups on pain intensity, disability, catastrophising, anxiety, and stress, whereby both groups demonstrated a significant reduction on these outcome measures. There was a significant main effect of time for both tDCS groups on quality of life, whereby both groups demonstrated a significant improvement in quality of life. There was no significant main effect of tDCS group or interaction between tDCS group and time on pain intensity, disability, catastrophising, anxiety, stress, and quality of life. These findings suggest anodal-tDCS over left-DLPFC is no more effective than sham-tDCS in improving cognition, pain experience, and psychological health in those with CLBP.
Impact of Medical Cannabis Treatment on Healthcare Utilization in Patients with Post-traumatic Stress Disorder: A Retrospective Cohort Study
Authors: Doucette Mitchell L. , Macfarlan D. Luke , Kasabuski Mark , Chin Junella , Fisher Emily
Published: November 2024

Introduction

Medical cannabis is increasingly used as a therapy for managing post-traumatic stress disorder (PTSD). Patients with PTSD often have high healthcare utilization rates, particularly for acute services. This study examines the association between medical cannabis treatment and healthcare utilization among patients with PTSD.

Methods

We conducted a retrospective cohort study using cross-sectional data with tem-poral elements, derived from administrative records provided by Leafwell, among patients with PTSD. The cohort was defined based on medical cannabis use: the treated group included patients who had used medical cannabis for at least one year (returning for medical card renewal), while the untreated group consisted of cannabis-naive patients reporting no prior cannabis use. The primary outcomes were healthcare utilization within the past six months, including at least one urgent care visit, emergency department (ED) visit, or hospitalization related to their primary medical condition. We used inverse probability weighting with regression adjustment (IPWRA) to estimate the average treatment effect (ATE) of medical cannabis use on healthcare utilization, controlling for key demographics and health factors, including PTSD severity. Sensitivity analyses were conducted to assess the robustness of our findings.

Results

Among the 1,946 participants, the treated group (n = 1,261) had significantly lower healthcare utilization rates compared to the untreated group (n = 685). Using the doubly robust IPWRA model, medical cannabis treatment was associated with a significant 35.6% reduction in urgent care visits (coefficient = -0.024, Standard Error (SE) = 0.0117) and a 35.1% reduction in ED visits (coefficient = -0.027, SE = 0.0124). Hospitalization rates were 26.3% lower among the treated group but did not reach statistical significance. Sensitivity analyses utilizing alternative ATE estimation strategies displayed consistent reductions in urgent care and ED visits among cannabis users, though hospitalizations remained non-significant. Adjusting the IPWRA model’s tolerance levels strengthened the found associations while maintaining strong covariate balance. Fewer than 2% of the treated group reported an adverse event.

Discussion

These findings suggest that medical cannabis treatment among patients with PTSD may be associated with reduced utilization of urgent care and ED services. This relationship remains robust across multiple statistical models and sensitivity analyses, underscoring the potential role of medical cannabis in reducing acute healthcare needs in this population. Further longitudinal research is warranted to explore causality and assess its impact on hospitalization rates.
Sleep Quality Mediates the Relationship Between Sleep Hygiene and Psychological Stress Among Adults With Multiple Cardiovascular Risk Factors
Authors: Liu Xiaoyue , Li Junxin , Hu Jinyu , Fletcher Jason , Commodore-Mensah Yvonne , Himmelfarb Cheryl R.
Published: December 2024

Background

Poor sleep quality and psychological stress are interrelated and disproportionately affect adults with multiple cardiovascular disease (CVD) risk factors. Maintaining an optimal home environment and engaging in healthy bedtime behaviors are important components of sleep hygiene practices that influence sleep health and mental well-being. However, research is scarce in exploring the associations between sleep hygiene, sleep quality, and psychological stress among adults with multiple CVD risk factors.

Methods

A cross-sectional study was conducted with 300 adults diagnosed with hypertension and type 2 diabetes. Individuals were recruited from a large academic health center and were asked to complete an online survey. Sleep hygiene was assessed by nine individual factors focusing on negative household environment (safety, physical comfort, temperature, and light) and poor bedtime behaviors (watching TV, playing video games, using small screens, and eating) and by a composite score. Multiple regression and mediation analysis with bootstrapping were employed to examine the associations.

Results

Of the sample, 78% reported poor sleep quality and 44% reported high psychological stress. Individual sleep hygiene factors as well as the composite score were significantly associated with poorer sleep quality and higher psychological stress. Sleep quality mediated the association between the composite score and psychological stress (Indirect effect: 0.16; 95% bootstrap confidence interval: 0.04-0.35).

Conclusions

The study highlights strong links between sleep hygiene, sleep quality, and psychological stress. Although causality cannot be established, current evidence suggests that promoting home environment and bedtime behaviors may alleviate sleep and psychological burdens in adults with multiple CVD risk factors.

CLINICAL PERSPECTIVE

What Is New?

Adults with hypertension and type 2 diabetes often experience poor sleep quality and elevated psychological stress.

Room environment and bedtime behaviors are important components of sleep hygiene practices that strongly associate with sleep quality and mental well-being.

Sleep quality may serve as a mediating factor between sleep hygiene and psychological stress.

What Are the Clinical Implications?

Enhancing room environment and bedtime behaviors is crucial for adults with multiple cardiovascular disease risk factors.

Given the crucial roles of both sleep and psychological stress in cardiovascular health, promoting modifiable sleep hygiene practices may be an effective strategy to mitigate health risks in this population.
Development of the Incompatible Insect Technique targeting Aedes albopictus: introgression of a wild nuclear background restores the performance of males artificially infected with Wolbachia
Authors: Lejarre Quentin , Scussel Sarah , Esnault Jérémy , Gaudillat Benjamin , Duployer Marianne , Mavingui Patrick , Tortosa Pablo , Cattel Julien
Published: November 2024

The bacterium Wolbachia pipientis is increasingly studied for its potential use in controlling insect vectors or pests due to its ability to induce Cytoplasmic Incompatibility (CI). CI can be exploited by establishing an opportune Wolbachia infection in a targeted insect species through trans-infection and then releasing the infected males into the environment as sterilizing agents. Several host life history traits (LHT) have been reported to be negatively affected by artificial Wolbachia infection. Wolbachia is often considered as the causative agent of these detrimental effects, and the importance of the host’s genetic origins in the outcome of trans-infection is generally overlooked. In this study, we investigated the impact of host genetic background using an Aedes albopictus line recently trans-infected with wPip from Culex pipiens mosquito, which exhibited some fitness costs. We measured several LHTs including fecundity, egg hatch rate and male mating competitiveness in the incompatible line after four rounds of introgression aiming at restoring genetic diversity in the nuclear genome. Our results show that introgression with a wild genetic background restored most fitness traits and conferred a mating competitiveness comparable to that of wild males. Finally, we show that introgression leads to faster and stronger population suppression under laboratory conditions. Overall, our data support that host genome plays a decisive role in determining the fitness of Wolbachia infected incompatible males.
Structure and organization of full-length Epidermal Growth Factor Receptor in extracellular vesicles by cryo-electron tomography
Authors: Gonzalez-Magaldi Monica , Gullapalli Anuradha , Papoulas Ophelia , Liu Chang , Leung Adelaide Y.-H. , Guo Luqiang , Brilot Axel , Marcotte Edward M. , Ke Zunlong , Leahy Daniel J.
Published: November 2024

We report here transport of the Epidermal Growth Factor Receptor (EGFR), Insulin Receptor, 7-pass transmembrane receptor Smoothened, and 13-pass Sodium-iodide symporter to extracellular vesicles (EVs) for structural and functional studies. Mass spectrometry confirmed the transported proteins as the most abundant in EV membranes, and the presence of many receptor-interacting proteins demonstrates the utility of EVs for characterizing membrane protein interactomes. Cryo-electron tomography of EGFR-containing EVs reveals that EGFR forms clusters in the presence of EGF with a ∼3 nm gap between the inner membrane and cytoplasmic density. EGFR extracellular regions do not form regular arrays, suggesting that clustering is mediated by the intracellular region. Subtomogram averaging of the EGFR extracellular region (ECR) yielded a 15 Å map into which the crystal structure of the ligand-bound EGFR ECR dimer fits well. These findings refine our understanding of EGFR activation, clustering, and signaling, and they establish EVs as a versatile platform for structural and functional characterization of human membrane proteins in a native-like environment.

Significance Statement

Atomic or near-atomic resolution structural studies of proteins embedded in cell membranes have proven challenging. We show that transporting integral membrane proteins to cell-derived extracellular vesicles enables structural and functional studies of human membrane proteins in a native membrane environment. We have used this approach to visualize an active form of full-length Epidermal Growth Factor Receptor (EGFR) and show that it forms clusters in the membrane and projects its cytoplasmic signaling domains ∼3 nm away from the membrane surface. EGFR is essential for normal development, but abnormal EGFR activity is associated with several human cancers and is the target of many anticancer therapies. Our studies refine current models of how ligand binding to EGFR transmits signals across cell membranes.
Machine Learning Approaches for Survival Prediction in Bladder Cancer: A Single-Center Analysis of Clinical and Inflammatory Markers
Authors: Causio Francesco Andrea , De Vita Vittorio , Nappi Andrea , Sawaya Melissa , Rocco Bernardo , Foschi Nazario , Maioriello Giuseppe , Russo Pierluigi
Published: November 2024

This study investigated the application of machine learning algorithms for survival prediction in bladder cancer patients undergoing cystectomy. We analyzed retrospective data from 370 patients, developing predictive models for disease-free survival (DFS), overall survival (OS), and cause of death. Multiple machine learning approaches were employed, including linear regression, random forests, gradient boosting, support vector machines, and neural networks. The models achieved mean absolute errors of 22-23 months for survival predictions and 66.67% accuracy in cause-of-death classification. Clinical T-stage emerged as the strongest predictor, while the Systemic Immune-Inflammation Index (SII) demonstrated a consistent negative correlation with survival outcomes. An unexpected positive correlation between age and survival was observed, possibly reflecting selection bias in surgical candidates. The study’s findings suggest that machine learning approaches, despite current limitations, offer promising tools for risk stratification in clinical trial design and patient allocation, though further refinement is needed for individual prognostication.
EasyPubPlot: a shiny web application for rapid omics data exploration and visualization
Authors: Tien Nguyen Tran Nam , Thu Nguyen Quang , Kim Dong Hyun , Park Seongoh , Long Nguyen Phuoc
Published: November 2024

Computational toolkits for data exploration and visualization from widely used omics platforms often lack flexibility and customization. While many tools generate standardized output, advanced programming skills are necessary to create high-quality visualizations. Therefore, user-friendly tools that simplify this crucial yet time-consuming step are essential. We developed EasyPubPlot (Easy Publishable Plotting), a straightforward, easy-to-use, user experience-oriented, open-source, and shiny web application along with its associated R package to streamline data exploration and visualization for functional omics-empowered research. EasyPubPlot generates publishable scores plots, volcano plots, heatmaps, box plots, dot plots, and bubble plots with minimal necessary steps. The tool was designed to guide new users for accurate and efficient navigation. Step-by-step tutorials for each type of plot are also provided. Herein, we demonstrated EasyPubPlot’s competent functionality and versatility by showcasing metabolomics and transcriptomics data. Collectively, EasyPubPlot reduces the gap between data analysis and stunning visualization, thereby diminishing friction and focusing on science. The app can be downloaded and installed locally (https://github.com/Pharmaco-OmicsLab/EasyPubPlot) or used through a web application (https://pharmaco-omicslab.shinyapps.io/EasyPubPlot).
Small-Angle and Quasi-Elastic Neutron Scattering from Polydisperse Oligolamellar Vesicles Containing Glycolipids
Authors: Bange Lukas , Rahimzadeh Amin , Mukhina Tetiana , von Klitzing Regine , Hoffmann Ingo , Schneck Emanuel
Published: November 2024

Glycolipids are known to stabilize biomembrane multilayers through preferential sugar-sugar interactions that act as weak transient membrane cross-links. Here, we use small-angle and quasi-elastic neutron scattering on oligolamellar phospholipid vesicles containing defined glycolipid fractions in order to elucidate the influence of glycolipids on membrane mechanics and dynamics. Small-angle neutron scattering (SANS) reveals that the oligolamellar vesicles (OLVs) obtained by extrusion are polydisperse with regard to the number of lamellae,n, which renders the interpretation of the quasi-elastic neutron spin echo (NSE) data non-trivial. To overcome this problem, we propose a method to model the NSE data in a rigorous fashion based on the obtained histograms ofnand on theirq-dependent intensity-weighted contribution. This procedure yields meaningful values for the bending rigidity of individual lipid membranes and insights into the mechanical coupling between adjacent membrane lamellae, including the effect of the glycolipids.