bluuebunny/crossref_metadata_2025 huggingface dataset:
Eye-Opening Effect Achieved by Modified Transconjunctival Lower Blepharoplasty
Authors: Kubo Takayuki
Published: October 2024

Background

Enophthalmia (abnormally sunken eyeball in the socket) and ptotic upper lid, as well as lower lid symptoms, are commonly observed in patients seeking periorbital rejuvenation.

Objectives

The aim of this study was to assess the effect of transconjunctival lower blepharoplasty (TCLB) modified by adding deframing and decompression maneuvers to the lower orbital fat compartment (LOFC) and its support structures to obtain better results in both the lower and upper lids.

Methods

Modified TCLB was performed in patients with lower eyelid symptoms. Palpebral fissure height (PFH) (the distance between the upper and lower eyelids in vertical alignment with the center of the pupil) was measured before surgery and 12 months postoperatively from 3-dimensional photographs. These data were compared to validate the postoperative eye-opening effect. The weight of the excised fat from each LOFC was also measured and compared.

Results

Forty patients (36 females and 4 males) who underwent modified TCLB were followed up 12 months postoperatively. Mean [standard deviation] preoperative PFHs were 8.41 [1.15] mm (range, 6.1-10.7 mm) for the right and 8.41 [1.12] mm (range, 5.5-10.4 mm) for the left. Postoperative PFHs were 9.26 [0.95] mm (range, 6.4-11.1 mm) for the right and 9.21 [0.94] mm (range, 6.2-11.1 mm) for the left. The improvement in postoperative eye opening was statistically significant. The total excised LOFC was 0.43 [0.24] g (range, 0-1.2 g) for the right and 0.42 [0.25] g (range, 0-1.5 g) for the left. The largest amount of fat was excised bilaterally from the lateral LOFC, and the difference was statistically significant.

Conclusions

The results after the modified TCLB clearly demonstrate increased eye-opening ability and marked resolution of observable symptoms. The anatomical dynamics of the orbit involved in this procedure are detailed through scientific data.

Level of Evidence: 4 (Therapeutic)
MSIreg: an R package for unsupervised coregistration of mass spectrometry and H&E images
Authors: Lakkimsetty Sai Srikanth , Weber Andreas , Bemis Kylie A , Stehl Verena , Bronsert Peter , Föll Melanie C , Vitek Olga
Published: October 2024

Joint analysis of mass spectrometry images (MS images) and microscopy images of hematoxylin and eosin (H&E) stained tissues assists pathologists in characterizing the morphological structure of the tissues, and in performing diagnosis. Unfortunately, the analysis is undermined by substantial differences between these modalities in terms of aspect ratios, spatial resolution, number of channels in each image, as well as by large global or small local elastic spatial deformations of one image with respect to the other. Therefore, accurate coregistration of the images is a critical pre-requisite for their joint interpretation. We introduce MSIreg, an open-source R package for coregistration of MSI and H&E images. MSIreg is designed for high-dimensional MSI experiments where each spatial location is represented by thousands of mass features. Unlike most existing coregistration methods, MSIreg implements a landmark free workflow, and quantitative metrics for performance evaluation. We evaluate the performance of MSIreg on six case studies, including coregistration of contiguous tissues with large deformations, as well as simultaneous coregistration of 29 tissue microarray cores.

Availability and implementation

The R package, installation instructions, and fully reproducible vignettes describing methods and Case Studies are available open-source under the GPL-3.0 license at https://github.com/sslakkimsetty/msireg/.
DPNN-ac4C: a dual-path neural network with self-attention mechanism for identification of N4-acetylcytidine (ac4C) in mRNA
Authors: Yuan Jiahao , Wang Ziyi , Pan Zhuoyu , Li Aohan , Zhang Zilong , Cui Feifei
Published: October 2024

Motivation

The modification of N4-acetylcytidine (ac4C) in RNA is a conserved epigenetic mark that plays a crucial role in post-transcriptional regulation, mRNA stability, and translation efficiency. Traditional methods for detecting ac4C modifications are laborious and costly, necessitating the development of efficient computational approaches for accurate identification of ac4C sites in mRNA.

Results

We present DPNN-ac4C, a dual-path neural network with a self-attention mechanism for the identification of ac4C sites in mRNA. Our model integrates embedding modules, bidirectional GRU networks, convolutional neural networks, and self-attention to capture both local and global features of RNA sequences. Extensive evaluations demonstrate that DPNN-ac4C outperforms existing models, achieving an AUROC of 91.03%, accuracy of 82.78%, MCC of 65.78%, and specificity of 84.78% on an independent test set. Moreover, DPNN-ac4C exhibits robustness under the Fast Gradient Method attack, maintaining a high level of accuracy in practical applications.

Availability and implementation

The model code and dataset are publicly available on GitHub (https://github.com/shock1ng/DPNN-ac4C).
On role models and Joe LeDoux
Authors: Josselyn Sheena A
Published: October 2024

Joseph LeDoux is a pioneering neuroscientist who has made profound discoveries that continue to impact our understanding of the neural basis of emotion and memory, particularly the role of the amygdala in threat conditioning. LeDoux’s trailblazing and elegant studies were some of the first to examine the circuit basis of behavior. His work combined techniques to trace pathways into and out of the amygdala important for threat conditioning and related behaviors. Since that time, these types of circuit tracing studies have exploded in popularity across neuroscience, and I would argue, we all owe a debt to LeDoux for this. LeDoux has made numerous additional contributions to neuroscience and, by bringing emotion back to neuroscience, has helped unite neuroscience with psychology. A gifted writer with a knack for communicating complicated scientific ideas in an accessible manner, LeDoux has become an ambassador of science who uses his love of music to help educate and inspire. Perhaps more important than these laudable scientific achievements, LeDoux is also a true “gentleman” of science, showing that science need not be a contact sport. Here, I give a personal account on why Joseph LeDoux is one of my scientific role models.
Dynamic prediction of kidney allograft and patient survival using post-transplant estimated glomerular filtration rate trajectory
Authors: Bakar Khandoker Shuvo , Teixeira-Pinto Armando , Gately Ryan , Boroumand Farzaneh , Lim Wai H , Wong Germaine
Published: October 2024

Background

Allograft loss is the most feared outcome of kidney transplant recipients. We aimed to develop a dynamic Bayesian model using estimated glomerular filtration rate (eGFR) trajectories to predict long-term allograft and patient survivals.

Methods

We used data from the Australian and New Zealand Dialysis and Transplant registry and included all adult kidney transplant recipients (1980–2017) in Australia (derivation cohort) and New Zealand (NZ, validation cohort). Using a joint model, the temporal changes of eGFR trajectories were used to predict patient and allograft survivals.

Results

The cohort composed of 14 915 kidney transplant recipients [12 777 (86%) from Australia and 2138 (14%) from NZ] who were followed for a median of 8.9 years. In the derivation cohort, eGFR trajectory was inversely associated with allograft loss [every 10 ml/min/1.73 m2 reduction in eGFR, adjusted hazard ratio [HR, 95% credible intervals (95%CI) 1.31 (1.23–1.39)] and death [1.12 (1.10–1.14)]. Similar estimates were observed in the validation cohort. The respective dynamic area under curve (AUC) (95%CI) estimates for predicting allograft loss at 5-years post-transplantation were 0.83 (0.75–0.91) and 0.81 (0.68–0.93) for the derivation and validation cohorts.

Conclusion

This straightforward model, using a single metric of eGFR trajectory, shows good model performance, and effectively distinguish transplant recipients who are at risk of death and allograft loss from those who are not. This simple bedside tool may facilitate early identification of individuals at risk of allograft loss and death.
Like a Punch in the Gut: A Novel Perspective On Annual Recurrences of Ulcerative Colitis
Authors: Johnston Sasha , Fraser Aileen , Biddle Carrie , Wild Jennifer
Published: October 2024

Background

Ulcerative colitis (UC), a chronic inflammatory bowel disease, causes stomach pain, diarrhea, and rectal bleeding. The exact cause is unknown, but it is thought to involve genetic, environmental, and psychological factors. Some people experience annual flare-ups without obvious reason. This article adopts a theory-driven approach to consider how and why past traumatic events may contribute to annual flare-ups.

Methods

We applied learning theory, which explains the development of re-experiencing phenomena in post-traumatic stress disorder (PTSD), to better understand the occurrence of annual flares in patients living with UC.

Results

Two possibilities emerged in which associative learning may contribute to annual UC flares. First, flare-ups could be a physical response to sensory cues in the present that overlap with trauma experienced at the first onset of UC. Annual episodes may strengthen the UC flare as a learned physiological response to trauma reminders. Second, flare-ups may result from elevated stress due to trauma re-experiencing at anniversaries. Sensory features of the initial UC trauma may be associated with strong reactions, which generalize to similar stimuli, triggering re-experiencing symptoms and increasing psychological stress. Elevated stress raises glucocorticoid levels, promoting UC-specific inflammation. Stimulus discrimination from cognitive therapy for PTSD may help to over-ride the associations that have formed between sensory features of past trauma, linked reactions, and similar cues in the present.

Conclusions

Research is needed to understand how traumatic events influence the onset and recurrence of ulcerative colitis, as well as the potential benefits of stimulus discrimination for reducing the frequency of annual flares.
Three-layered functionally specialized nest structures enhance strength and water retention in mounds of Globitermes sulphureus (Blattodea: Termitidae)
Authors: Chiu Chun-I , Attasopa Korrawat , Wongkoon Sinsap , Chromkaew Yupa , Liao Hauchuan , Kuan Kuan-Chih , Suttiprapan Piyawan , Guswenrivo Ikhsan , Li Hou-Feng , Sripontan Yuwatida
Published: October 2024

Termite mounds are a ubiquitous feature of savanna ecosystems, yet the mechanisms by which termites (Blattodea: Termitoidae) mitigate the challenges posed by seasonal drought and flooding through mound construction remain insufficiently explored. This study investigates the material properties, water retention capabilities, and resistance to raindrop penetration across three distinct layers of Globitermes sulphureus (Haviland, 1898) (Blattodea: Termitidae) nests. Our findings reveal a pronounced diversification and specialization of materials and functions across these layers. Specifically, the outer layer has decreased moisture permeability, the middle layer has enhanced resistance to water penetration, and the innermost layer has a high capacity for water retention. The integration of these functionally specialized layers provides a compelling evidence for explaining how these termites are able to adapt to the fluctuating environmental conditions characteristic of savanna ecosystems. Furthermore, this highlights the nest’s buffering capability against environmental stressors. The complexity of this construction, marked by a level of self-organization rarely observed in the animal kingdom, underscores a significant instance of architectural ingenuity among non-human builders.
Cardiac arrest in pregnancy with successful stabilization and delivery on veno-arterial extracorporeal membrane oxygenation: a case report
Authors: Burton Alice , Ratwatte Seshika , Zalcberg David , Morgan Matthew , Narayan Rajit , Cordina Rachael
Published: October 2024

Background

Cardiac arrest in pregnancy is rare. Clinicians need to adapt management to the altered anatomy and physiology of pregnancy, and the well-being of two patients (mother and foetus) may come into consideration. The medical literature has limited reports on outcomes following extracorporeal membrane oxygenation (ECMO) in pregnancy.

Case summary

We report the evaluation, management, and outcome of a woman with cardiac arrest and severe left ventricle (LV) dysfunction in mid-trimester of pregnancy. The previously well woman had tolerated two prior term pregnancies without complication. At 25 weeks of gestation, she presented to the hospital with breathlessness and vomiting after a pre-syncopal episode at home. She then had in-hospital cardiac arrest, managed initially with cardiopulmonary resuscitation. The LV was dilated, thin walled, and severely impaired (LV ejection fraction 14%), and there was a secundum atrial septal defect (ASD). She was supported with veno-arterial ECMO. Planned birth occurred 5 days post-arrest for maternal indication. Coronary angiography demonstrated 99% proximal left anterior descending artery stenosis and aneurysm, raising the possibility of previous subclinical Kawasaki disease. She underwent surgical revascularization and ASD closure. Both mother and infant made a good recovery.

Discussion

We report a case of cardiac arrest in pregnancy as first presentation of severe LV dysfunction. The case highlights the role of ECMO for cardiac arrest in pregnancy and outlines specific interventions and management concepts in this setting.
The emerging role of clonal haematopoiesis in the pathogenesis of dilated cardiomyopathy
Authors: Verdonschot Job A J , Fuster Jose J , Walsh Kenneth , Heymans Stephane R B
Published: October 2024

The increased sensitivity of novel DNA sequencing techniques has made it possible to identify somatic mutations in small circulating clones of haematopoietic stem cells. When the mutation affects a ‘driver’ gene, the mutant clone gains a competitive advantage and has the potential to expand over time, a phenomenon referred to as clonal haematopoiesis (CH), which is emerging as a new risk factor for various non-haematological conditions, most notably cardiovascular disease (e.g. heart failure). Dilated cardiomyopathy (DCM) is a form of non-ischaemic heart failure that is characterized by a heterogeneous aetiology. The first evidence is arising that CH plays an important role in the disease course in patients with DCM, and a strong association of CH with multiple aetiologies of DCM has been described (e.g. inflammation, chemotherapy, and atrial fibrillation). The myocardial inflammation induced by CH may be an important trigger for DCM development for an already susceptible heart, e.g. in the presence of genetic variants, environmental triggers, and comorbidities. Studies investigating the role of CH in the pathogenesis of DCM are expected to increase rapidly. To move the field forward, it will be important to report the methodology and results in a standardized manner, so results can be combined and compared. The accurate measurement of CH in patients with DCM can provide guidance of specific (anti-inflammatory) therapies, as mutations in the CH driver genes prime the inflammasome pathway.
Are drivers recurring or ephemeral? observations from serial mapping of persistent atrial fibrillation
Authors: Hunt Bram , Kwan Eugene , Paccione Eric , Orkild Benjamin , Yazaki Kyoichiro , Bergquist Jake , Dong Jiawei , MacLeod Robert S , Dosdall Derek J , Ranjan Ravi
Published: October 2024

Aims

Rotational re-entries and ectopic foci, or ‘drivers’, are proposed mechanisms for persistent atrial fibrillation (persAF), but driver-based interventions have had mixed success in clinical trials. Selective targeting of drivers with multi-month stability may improve these interventions, but no prior work has investigated whether drivers can be stable on such a long timescale.

Objective

We hypothesized that drivers could recur even several months after initial observation.

Methods and results

We performed serial electrophysiology studies on paced canines (n = 18, 27–35 kg) at 1−, 3−, and 6 months post-initiation of continual persAF. Using a high-density 64-electrode catheter, we captured endocardial electrograms in the left atrium (LA) and right atrium (RA) to determine the presence of drivers at each major anatomical site. We defined drivers that were repeatedly observed across consecutive studies to be recurrent. The mean probability that any driver would recur was 66% (LA: 73%, RA: 41%). We also found evidence of ‘multi-recurring’ drivers, i.e. those seen in all three studies. Multi-recurring drivers constituted 53% of initially observed drivers with at least one found in 92% of animals, and we found more multi-recurring drivers per animal than predicted by random chance (2.6 ± 1.5 vs. 1.2 ± 1.1, P < 0.001). Driver sites showed more enhancement than non-drivers during late gadolinium enhancement-magnetic resonance imaging (P = 0.04), but we observed no relationship between enhancement and driver recurrence type.

Conclusion

We observed recurring drivers over a 6-month period at fixed locations, confirming our hypothesis. We also found drivers to be associated with fibrosis, implying a structural basis.
Associations Between Loneliness, Epigenetic Aging, and Multimorbidity Through Older Adulthood
Authors: Freilich Colin D , Markon Kristian E , Mann Frank D , Cole Steve W , Krueger Robert F
Published: October 2024

Objectives

Loneliness is a pressing public health concern, but the mechanisms by which it leads to declining physical health are uncertain. Prior work has begun to explore epigenetic pathways, with some evidence suggesting a link between loneliness and DNA methylation, though it is unclear whether epigenetic variation can help explain loneliness–health associations.

Methods

Associations between loneliness and epigenetic age acceleration (EAA) were estimated, as well as the degree to which EAA mediated and moderated the association between loneliness and the development of chronic physical health conditions (multimorbidity) in older adulthood. The sample consisted of Health and Retirement Study participants who provided blood draws and consented to methylation profiling (n = 4,018).

Results

Baseline loneliness was associated with greater EAA in the GrimAge measure net of demographic and behavioral covariates (β = 0.07, p = .003). Loneliness and GrimAge each predicted increasing condition counts, but there was no evidence of an interactive effect. The association between loneliness and increasing condition counts was, however, significantly mediated by GrimAge (indirect path β = 0.020, p = .003).

Discussion

These results suggest that the impact of loneliness on multimorbidity may, in part, operate through DNA methylation. The specific intermediary, physiological mechanisms that are involved will require further research, but EAA measures like GrimAge are promising in helping to understand the health impacts of loneliness.
Theoretical investigation of the excitation of leaky modes for multilayered models
Authors: Wu Bo , Shi Caiwang , Chen Xiaofei , Zhang Qi
Published: October 2024

The dispersion analysis with array-based methods enables us to detect and analyse the multimode dispersive waves with weak amplitudes. Over the past years, there has been widespread extraction of higher normal modes from earthquake records and ambient noise, which have been extensively employed in near-surface and crustal investigations. Notably, the frequent reporting of leaky modes in recent observations has gained significant attention. This is because leaky modes can provide more constraints on subsurface structures. Particularly, a subset of leaky modes is found to be sensitive to P-wave velocities, which has the potential to compensate for the limitations of traditional surface wave inversion. Nevertheless, due to the lack of knowledge of the excitation and practical application of leaky modes, it is urgent to have an effective guide in selecting certain leaky modes for practical inversion combined with other imaging methods. To this end, the theoretical investigation into the excitation of leaky modes for multilayered models is undertaken. By computing theoretical seismograms for various source mechanisms and source depths with the discrete wavenumber and the normal-mode summation methods, respectively, the qualitative evaluation of the leaky-mode contributions to the synthesized seismograms is conducted. Additionally, the impact of the source depth for the same source mechanism is meticulously examined by the dispersion spectra. Furthermore, with the accurate computation of leaky modes, we categorize the leaky modes into PL and OP (organ-pipe) modes according to their distinctive properties, that is, their attenuation and eigen-displacements, which may be used to explain very well the occurrence of certain leaky modes on the dispersion spectrum and be indicative of the reasonable choice of PL modes to put them into practical inversion for P-velocity structures.
A new semi-analytic model for Stern-layer polarization in pore throats
Authors: Kreith D , Leroy P , Bücker M
Published: October 2024

To explain induced polarization, membrane polarization is often referred to as a relevant process taking place in granular media – particularly, when narrow pore throats are present. This polarization effect is based on the membrane-like behaviour of pore throats caused by the presence of an usually negative charge on the pore surface, that influences charge transport in the pore fluid. Existing analytical, 1D models describe the pore system as a series of cylindrical pores with different radii and lengths. The polarization response is calculated by solving the Poisson–Nernst–Planck system for the current densities of one single anion and one single cation species representing the charge transport in the electrolyte and the diffuse layer at the pore surface. To include charge transport in the Stern layer, cations in the Stern layer have so far simply been considered by increasing the concentration of the diffuse layer cations. As we know from numerical modelling, this approach fails to predict the polarization response when the Stern layer is significantly charged. Here, we present a new semi-analytical model that treats the Stern-layer cations as a separate ion species and allows the Stern layer to polarize individually. To validate our new model, we compare it to the previously used analytical model and numerical simulations for different relative charges in Stern- and diffuse layer. We also use electrostatic surface-complexation models for two mineral surfaces (quartz and montmorillonite) to simulate the response of real geologic material under varying chemical conditions. This work is a step forward for considering realistic pore properties in induced-polarization modelling.
No Surprises Act independent dispute resolution outcomes for emergency services
Authors: Duffy Erin L , Garmon Christopher , Adler Loren , Biener Adam , Trish Erin
Published: October 2024

The No Surprises Act banned surprise billing and established a final-offer arbitration system, independent dispute resolution (IDR), to resolve disagreements between health plans and providers. One factor that arbiters must consider in the IDR process is the qualifying payment amount (QPA), the median contracted rate for the same or similar service in the same market as computed by health plans. We analyzed public IDR data from 2023 for the most common disputed professional service: evaluation and management of a moderate to severe emergency medicine visit. Providers won 86% of cases, with mean decisions 2.7 times the QPA. Private equity-backed providers won more often and higher monetary awards than other providers. The mean QPA was 2.4 times Medicare payments. Disputes were dominated by a small group of health plans and providers, so payments may not reflect the overall market for emergency services.
Predicting Outcomes in Hospitalized Patients With Acute Severe Ulcerative Colitis in a Prospective Multicenter Cohort
Authors: Chaaban Lara , Cohen Benjamin , Cross Raymond K , Kayal Maia , Long Millie , Ananthakrishnan Ashwin , Melia Joanna
Published: October 2024

Background and Aims

Acute severe ulcerative colitis (UC) (ASUC) requiring hospitalization affects up to 1 in 4 patients with UC. There is a paucity of prospective and multicenter clinical cohorts to study treatment trends and predictors of disease outcomes. Here, we conduct a US-based multicenter prospective clinical cohort of ASUC to study predictors of the need for medical rescue therapy and colectomy.

Methods

A total of 94 patients hospitalized for ASUC were included across 5 academic centers from December 2018 to December 2021. Demographic, clinical, and laboratory data were collected throughout the hospitalization. Patients were followed up to 1-year post-hospitalization to identify predictors of the need for rescue therapy and colectomy.

Results

A total of 21 (22.3%) patients required colectomy within 1 year of admission with 11 (12%) requiring colectomy during the index admission. On multivariate analyses, a BMI < 21.5 kg/m2 (OR = 6.16, P = .02), a simple clinical colitis activity index (SCCAI) greater than 8 (OR = 14.44, P = .01) and an albumin level at admission lower than 2.4 g/dL (OR = 10.61, P = .04) were significant predictors of inpatient colectomy after adjusting for sex, age, and duration of disease.

Conclusions

In a prospective, multicenter cohort of patients hospitalized with ASUC, BMI, SCCAI, and albumin at admission were important determinants of colectomy risk during the index hospitalization and within 1 year of admission. Colectomy rates remain high—22.3% in this cohort across 5 academic, tertiary care centers—underscoring the need to identify the highest-risk patients, establish novel treatment and care paradigms, and examine opportunities to standardize care.
Long-term exposure to PM2.5 and mortality: a national health insurance cohort study
Authors: Moon Jeongmin , Kim Ejin , Jang Hyemin , Song Insung , Kwon Dohoon , Kang Cinoo , Oh Jieun , Park Jinah , Kim Ayoung , Choi Moonjung , Cha Yaerin , Kim Ho , Lee Whanhee
Published: October 2024

Background

Previous studies with large data have been widely reported that exposure to fine particulate matter (PM2.5) is associated with all-cause mortality; however, most of these studies adopted ecological time-series designs or have included limited study areas or individuals residing in well-monitored urban areas. However, nationwide cohort studies including cause-specific mortalities with different age groups were sparse. Therefore, this study examined the association between PM2.5 and cause-specific mortality in South Korea using the nationwide cohort.

Methods

A longitudinal cohort with 187 917 National Health Insurance Service-National Sample Cohort participants aged 50–79 years in enrolment between 2002 and 2019 was used. Annual average PM2.5 was collected from a machine learning-based ensemble model (a test R2 = 0.87) as an exposure. We performed a time-varying Cox regression model to examine the association between long-term PM2.5 exposure and mortality. To reduce the potential estimation bias, we adopted generalized propensity score weighting method.

Results

The association with long-term PM2.5 (2-year moving average) was prominent in mortalities related to diabetes mellitus [hazard ratio (HR): 1.03 (95% CI: 1.01, 1.06)], circulatory diseases [HR: 1.02 (95% CI: 1.00, 1.03)] and cancer [HR: 1.01 (95% CI: 1.00, 1.02)]. Meanwhile, circulatory-related mortalities were associated with a longer PM2.5 exposure period (1 or 2-year lags), whereas respiratory-related mortalities were associated with current-year PM2.5 exposure. In addition, the association with PM2.5 was more evident in people aged 50–64 years than in people aged 65–79 years, especially in heart failure-related deaths.

Conclusions

This study identified the hypothesis that long-term exposure to PM2.5 is associated with mortality, and the association might be different by causes of death. Our result highlights a novel vulnerable population: the middle-aged population with risk factors related to heart failure.
Khovanov Algebras for the Periplectic Lie Superalgebras
Authors: Nehme Jonas
Published: October 2024

The periplectic Lie superalgebra $\mathfrak{p}(n)$ is one of the most mysterious and least understood simple classical Lie superalgebras with reductive even part. We approach the study of its finite dimensional representation theory in terms of Schur–Weyl duality. We provide an idempotent version of its centralizer, that is, the super Brauer algebra. We use this to describe explicitly the endomorphism ring of a projective generator for $\mathfrak{p}(n)$ resembling the Khovanov algebra of [ 5]. We also give a diagrammatic description of the translation functors from [ 1] in terms of certain bimodules and study their effect on projective, standard, costandard, and irreducible modules. These results will be used to classify irreducible summands in $V^{\otimes d}$, compute $\operatorname{Ext}^{1}$ between irreducible modules and show that $\mathfrak{p}(n)\operatorname{-mod}$ does not admit a Koszul grading.
Stable STFT Phase Retrieval and Poincaré Inequalities
Authors: Rathmair Martin
Published: October 2024

In recent work [P. Grohs and M. Rathmair. Stable Gabor Phase Retrieval and Spectral Clustering. Communications on Pure and Applied Mathematics (2018) and P. Grohs and M. Rathmair. Stable Gabor phase retrieval for multivariate functions. Journal of the European Mathematical Society (2021)], the instabilities of Gabor phase retrieval problem, that is, reconstructing $ f\in L^{2}(\mathbb{R})$ from its spectrogram, $|\mathcal{V}_{g} f|$ where $$ \begin{align*} & \mathcal{V}_g f(x,\xi) = \int_{\mathbb{R}} f(t)\overline{g(t-x)}e^{-2\pi i \xi t}\,\mbox{d}t, \end{align*} $$ have been classified in terms of the connectivity of the measurements. These findings were however crucially restricted to the case where the window $g(t)=e^{-\pi t^{2}}$ is Gaussian. In this work we establish a corresponding result for a number of other window functions including the one-sided exponential $g(t)=e^{-t}{1\kern-3.4pt1}_{[0,\infty )}(t)$ and $g(t)=\exp (t-e^{t})$. As a by-product we establish a modified version of Poincaré’s inequality, which can be applied to non-differentiable functions and may be of independent interest.
Changes in Hepatic Steatosis Before and After Direct-Acting Antiviral Treatment in People With HIV and Hepatitis C Coinfection
Authors: Truscello Esther , Wang Shouao , Young Jim , Sebastiani Giada , Walmsley Sharon L , Hull Mark , Cooper Curtis , Klein Marina B
Published: October 2024

Background

Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections increase the risk of hepatic steatosis (HS), which in turn contribute to the severity and progression of liver disease. Direct-acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear.

Methods

HS was assessed using the controlled attenuation parameter (CAP) and the Hepatic Steatosis Index (HSI) in participants coinfected with HIV and HCV from the Canadian Coinfection Cohort. Changes in HS, before, during, and after successful DAA treatment were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides, and hazardous drinking).

Results

In total, 431 participants with at least 1 measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval [CrI], 1.6–4.9) before, and 3.9 dB/m (95% CrI, 1.9–5.9) after DAA treatment, irrespective of pretreatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI, −0.1 to 0.5) before and 0.2 (95% CrI, −0.1 to 0.5) after, but demonstrated a marked reduction during treatment −4.5 (95% CrI, −5.9 to −3.1).

Conclusions

When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV.
Signaling, interests, and domestic politics: What matters for US credibility in Taiwan
Authors: Fu Ronan Tse-min , Lee Elaine I-lien , Park Gene
Published: October 2024

There have been growing calls for a rethink of U.S. policy towards Taiwan. Some argue that the U.S. should signal stronger commitment to Taiwan to deter China and maintain peace. To do so, a growing number of commentators and policymakers advocate that the U.S. provide a clear security guarantee to Taiwan. Others have suggested deploying troops on Taiwanese soil again. These calls beg an empirical question, one central to the study of international politics: how much would such reassurance measures increase confidence that one country would defend another if attacked? We find that an alliance with the U.S. and the deployment of troops on Taiwan would meaningfully increase confidence in the U.S. even when controlling for other factors. By estimating the magnitude of the effect of other variables cited in the literature, we also contribute to the ongoing debate over their relative influence on credibility. Specifically, our evidence suggests that the perceived alignment of interests is the cornerstone of credibility. The degree of division in the domestic politics of the patron state, in this case the U.S., also is a crucial determinant of credibility.
Long-term stability of sufentanil quantified by UPLC–MS–MS in human plasma frozen for 11 years at −20°C
Authors: Wehrfritz Andreas , Schmidt Stefanie , Ihmsen Harald , Schüttler Jürgen , Jeleazcov Christian
Published: October 2024

The long-term stability of drug concentrations in human plasma samples, when stored under normal laboratory conditions over several years, is important for research purposes and clinical re-evaluation, and forensic toxicology. Fifty human plasma samples from a former clinical trial were re-analyzed after storage at −20°C for 11 years. Plasma samples were extracted using solid-phase extraction. Isotope labeled sufentanil-d5 was used as internal standard. Sufentanil plasma concentrations were determined by ultra-performance liquid chromatography with gradient elution, followed by tandem mass spectrometry with electrospray ionization. The linear dynamic range was 25–2500 pg/mL, the limit of detection was 10 pg/mL, and the lower limit of quantification was 25 pg/mL. Intra- and inter-assay error did not exceed 6%. The deviation of the measured sufentanil plasma concentrations between the re-analysis and the first analysis was −63 ± 14% (mean ± SD). Therefore, sufentanil concentrations in human plasma were not stable in samples frozen at −20°C over 11 years.
Dorsal agenesis of the pancreas: an incidental finding
Authors: Cauchi Daphne , Mangion Shaun , Cassar Noel
Published: October 2024

This case report focuses on a 29-year-old female who presented with acute abdominal pain at Mater Dei Hospital, Malta. Her clinical presentation, followed up by diagnostic imaging, led to the diagnosis of a rare congenital abnormality known as dorsal agenesis of the pancreas. This condition is characterized by the absence or underdevelopment of the dorsal portion of the pancreas, a crucial aspect of pancreatic anatomy and function. The following text details the clinical presentation, diagnostic findings, and the broader implications of dorsal pancreatic agenesis in medical practice, reflecting on the rarity of this condition and the complexity of its diagnosis and management.
State-space analysis of a continuous gravitational wave source with a pulsar timing array: inclusion of the pulsar terms
Authors: Kimpson Tom , Melatos Andrew , O’Leary Joseph , Carlin Julian B , Evans Robin J , Moran William , Cheunchitra Tong , Dong Wenhao , Dunn Liam , Greentree Julian , O’Neill Nicholas J , Suvorova Sofia , Thong Kok Hong , Vargas Andrés F
Published: October 2024

Pulsar timing arrays (PTA) can detect continuous nanohertz gravitational waves (GW) emitted by individual supermassive black hole binaries. The data analysis procedure can be formulated within a time-domain, state-space framework, in which the radio timing observations are related to a temporal sequence of latent states, namely the intrinsic pulsar spin frequency. The achromatic wandering of the pulsar spin frequency is tracked using a Kalman filter concurrently with the pulse frequency modulation induced by a GW from a single source. The modulation is the sum of terms proportional to the GW strain at the Earth and at every pulsar in the array. Here, we generalize previous state-space formulations of the PTA problem to include the pulsar terms; that is, we copy the pulsar terms from traditional, non-state-space analyses over to the state-space framework. The performance of the generalized Kalman filter is tested using astrophysically representative software injections in Gaussian measurement noise. It is shown that including the pulsar terms corrects for previously identified biases in the parameter estimates (especially the sky position of the source) which also arise in traditional matched-filter analyses that exclude the pulsar terms. Additionally, including the pulsar terms decreases the minimum detectable strain by 14 per cent. Overall, the study verifies that the pulsar terms do not raise any special extra impediments for the state-space framework, beyond those studied in traditional analyses. The inspiral-driven evolution of the wave frequency at the Earth and at the retarded time at every pulsar in the array is also investigated.
Nexus: a framework for controlled simulations of idealized galaxies
Authors: Tepper-García Thor , Bland-Hawthorn Joss , Vasiliev Eugene , Agertz Oscar , Teyssier Romain , Federrath Christoph
Published: October 2024

Motivated by the need for realistic, dynamically self-consistent, evolving galaxy models that avoid the complexity of full, and zoom-in, cosmological simulations, we have developed Nexus, an integral framework to create and evolve synthetic galaxies made of collisionless and gaseous components. Nexus leverages the power of publicly available, tried-and-tested packages: the stellar-dynamics, action-based library Action-based Galaxy Modelling Architecture (AGAMA); and the adaptive mesh refinement, N-body/hydrodynamical code Ramses, modified to meet our needs. In addition, we make use of a proprietary module to account for galaxy formation physics, including gas cooling and heating, star formation, stellar feedback, and chemical enrichment. Nexus’ basic functionality consists in the generation of bespoke initial conditions (ICs) for a diversity of galaxy models, which are advanced in time to simulate the galaxy’s evolution. The fully self-consistent ICs are generated with a distribution-function-based approach, as implemented in the galaxy modelling module of AGAMA – up to now restricted to collisionless components, extended in this work to treat two types of gaseous configurations: hot haloes and gas discs. Nexus allows constructing equilibrium models with disc gas fractions $0~\le ~f_{\rm {\rm gas}}~\le ~1$, appropriate to model both low- and high-redshift galaxies. Similarly, the framework is ideally suited to the study of galactic ecology, i.e. the dynamical interplay between stars and gas over billions of years. As a validation and illustration of our framework, we reproduce several isolated galaxy model setups reported in earlier studies, and present a new, ‘nested bar’ galaxy simulation. Future upgrades of Nexus will include magnetohydrodynamics and highly energetic particle (‘cosmic ray’) heating.
Predicting Phylogenetic Bootstrap Values via Machine Learning
Authors: Wiegert Julius , Höhler Dimitri , Haag Julia , Stamatakis Alexandros
Published: October 2024

Estimating the statistical robustness of the inferred tree(s) constitutes an integral part of most phylogenetic analyses. Commonly, one computes and assigns a branch support value to each inner branch of the inferred phylogeny. The still most widely used method for calculating branch support on trees inferred under maximum likelihood (ML) is the Standard, nonparametric Felsenstein bootstrap support (SBS). Due to the high computational cost of the SBS, a plethora of methods has been developed to approximate it, for instance, via the rapid bootstrap (RB) algorithm. There have also been attempts to devise faster, alternative support measures, such as the SH-aLRT (Shimodaira–Hasegawa-like approximate likelihood ratio test) or the UltraFast bootstrap 2 (UFBoot2) method. Those faster alternatives exhibit some limitations, such as the need to assess model violations (UFBoot2) or unstable behavior in the low support interval range (SH-aLRT). Here, we present the educated bootstrap guesser (EBG), a machine learning-based tool that predicts SBS branch support values for a given input phylogeny. EBG is on average 9.4 (σ=5.5) times faster than UFBoot2. EBG-based SBS estimates exhibit a median absolute error of 5 when predicting SBS values between 0 and 100. Furthermore, EBG also provides uncertainty measures for all per-branch SBS predictions and thereby allows for a more rigorous and careful interpretation. EBG can, for instance, predict SBS support values on a phylogeny comprising 1,654 SARS-CoV2 genome sequences within 3 h on a mid-class laptop. EBG is available under GNU GPL3.
Ancient Secretory Pathways Contributed to the Evolutionary Origin of an Ecologically Impactful Bioluminescence System
Authors: Mesrop Lisa Y , Minsky Geetanjali , Drummond Michael S , Goodheart Jessica A , Proulx Stephen R , Oakley Todd H
Published: October 2024

Evolutionary innovations in chemical secretion—such as the production of secondary metabolites, pheromones, and toxins—profoundly impact ecological interactions across a broad diversity of life. These secretory innovations may involve a “legacy-plus-innovation” mode of evolution, whereby new biochemical pathways are integrated with conserved secretory processes to create novel products. Among secretory innovations, bioluminescence is important because it evolved convergently many times to influence predator–prey interactions, while often producing courtship signals linked to increased rates of speciation. However, whether or not deeply conserved secretory genes are used in secretory bioluminescence remains unexplored. Here, we show that in the ostracod Vargula tsujii, the evolutionary novel c-luciferase gene is co-expressed with many conserved genes, including those related to toxin production and high-output protein secretion. Our results demonstrate that the legacy-plus-innovation mode of secretory evolution, previously applied to sensory modalities of olfaction, gustation, and nociception, also encompasses light-producing signals generated by bioluminescent secretions. This extension broadens the paradigm of secretory diversification to include not only chemical signals but also bioluminescent light as an important medium of ecological interaction and evolutionary innovation.
Development of hydrophobic tag purifying monophosphorylated RNA for chemical synthesis of capped mRNA and enzymatic synthesis of circular mRNA
Authors: Ototake Mami , Inagaki Masahito , Kimura Seigo , Onda Kaoru , Tada Mizuki , Kawaguchi Daisuke , Murase Hirotaka , Fukuchi Kosuke , Gao Yinuo , Kokubo Kengo , Acharyya Susit , Meng Zheyu , Ishida Tatsuma , Kawasaki Tairin , Abe Naoko , Hashiya Fumitaka , Kimura Yasuaki , Abe Hiroshi
Published: October 2024

We developed phosphorylation reagents with a nitrobenzyl hydrophobic tag and used them for 5′-phosphorylation of chemically or transcriptionally synthesized RNA. The capability of hydrophobic tags to synthesize 5′-monophosphorylated RNA was evaluated based on the yield of the desired oligonucleotides, stability of protecting groups during cleavage/deprotection, separation ability in reverse-phase HPLC (RP-HPLC), and deprotection efficiency after RP-HPLC purification. The results showed that a nitrobenzyl derivative with a tert-butyl group at the benzyl position was most suitable for RNA 5′-phosphorylation. Using the developed phosphorylation reagent, we chemically synthesized 5′-phosphorylated RNA and confirmed that it could be purified by RP-HPLC and the following deprotection. In addition, we demonstrated complete chemical synthesis of minimal mRNA by chemical capping of 5′-monophosphorylated RNA. Ribonucleoside 5′-monophosphates with hydrophobic protecting groups have also been developed and used as substrates to transcriptionally synthesize 5′-phosphorylated RNA with >1000 bases. From the mixture of the by-products and the desired RNA, only 5′-monophosphorylated RNA could be effectively isolated by RP-HPLC. Furthermore, monophosphorylated RNA can be converted into circular mRNA via RNA ligase-mediated cyclization. Circular mRNA expression of nanoluciferase in cultured cells and mice. These techniques are important for the production of chemically synthesized mRNA and circular mRNA.
Structure-based discovery of first inhibitors targeting the helicase activity of human PIF1
Authors: Wever Mark J A , Scommegna Francesca R , Egea-Rodriguez Sara , Dehghani-Tafti Saba , Brandao-Neto Jose , Poisson Jean-François , Helfrich Iris , Antson Alfred A , Rodeschini Vincent , Bax Ben , Roche Didier , Sanders Cyril M
Published: October 2024

PIF1 is a conserved helicase and G4 DNA binding and unwinding enzyme, with roles in genome stability. Human PIF1 (hPIF1) is poorly understood, but its functions can become critical for tumour cell survival during oncogene-driven replication stress. Here we report the discovery, via an X-ray crystallographic fragment screen (XChem), of hPIF1 DNA binding and unwinding inhibitors. A structure was obtained with a 4-phenylthiazol-2-amine fragment bound in a pocket between helicase domains 2A and 2B, with additional contacts to Valine 258 from domain 1A. The compound makes specific interactions, notably through Leucine 548 and Alanine 551, that constrain conformational adjustments between domains 2A and 2B, previously linked to ATP hydrolysis and DNA unwinding. We next synthesized a range of related compounds and characterized their effects on hPIF1 DNA-binding and helicase activity in vitro, expanding the structure activity relationship (SAR) around the initial hit. A systematic analysis of clinical cancer databases is also presented here, supporting the notion that hPIF1 upregulation may represent a specific cancer cell vulnerability. The research demonstrates that hPIF1 is a tractable target through 4-phenylthiazol-2-amine derivatives as inhibitors of its helicase action, setting a foundation for creation of a novel class of anti-cancer therapeutics.