bluuebunny/crossref_metadata_2025 huggingface dataset:
AI-enabled manufacturing process discovery
Authors: Quispe D , Kozjek D , Mozaffar M , Xue T , Cao J
Published: February 2025

Discovering manufacturing processes has been largely experienced-based. We propose a shift to a systematic approach driven by dependencies between energy inputs and performance outputs. Uncovering these dependencies across diverse process classes requires a universal language that characterizes process inputs and performances. Traditional manufacturing languages, with their individualized syntax and terminology, hinder the characterization across varying length scales and energy inputs. To enable the evaluation of process dependencies, we propose a broad manufacturing language that facilitates the characterization of diverse process classes, which include energy inputs, tool-material interactions, material compatibility, and performance outputs. We analyze the relationships between these characteristics by constructing a dataset of over 50 process classes, which we use to train a variational autoencoder (VAE) model. This generative model encodes our dataset into a 2D latent space, where we can explore, select, and generate processes based on desired performances and retrieve the corresponding process characteristics. After verifying the dependencies derived from the VAE model match with existing knowledge on manufacturing processes, we demonstrate the usefulness of using the model to discover new potential manufacturing processes through three illustrative cases.
Radiative Acceleration and X-ray Spectrum of Outflowing Pure Electron-Positron Pair Fireball in Magnetar Bursts
Authors: Wada Tomoki , Asano Katsuaki
Published: February 2025

An X-ray short burst associated with a Galactic fast radio burst was observed in 2020, distinguished by its X-ray cut-off energy significantly exceeding that of other X-ray short bursts. X-ray photons of these short bursts are believed to originate from fireballs within the magnetospheres of magnetars. If a fireball forms near a magnetic pole, it expands along the magnetic field lines, subsequently emitting photons and generating plasma outflows that may account for the observed radio bursts. We numerically study the radiative acceleration and X-ray spectrum of such outflowing fireballs consisting of pure electron-positron pairs and radiation, employing spherically symmetric relativistic radiation hydrodynamics calculations with the effects of strong magnetic fields. Using Monte-Carlo scheme in the radiation calculation, we consistently incorporate both the acceleration of the fluid by radiation and the scattering of radiation by the fluid, both of which are enhanced by the cyclotron resonant scattering. Our calculation reveals that cyclotron resonant scattering accelerates the plasma outflow significantly and broadens the X-ray spectrum. The plasma outflow is accelerated up to ultra-relativistic velocities, with Lorentz factors exceeding 100. The calculated X-ray spectrum broadened due to the scattering is similar to the observed X-ray spectrum in the Galactic fast radio burst.
vis-r: Quick radial profile modelling for radio interferometric visibilities
Authors: Kennedy Grant M
Published: February 2025

This paper describes a method for parametric radial profile modelling of radio interferometric visibility data. Image-based parametric modelling is common in the field of circumstellar debris disks, and high resolution ALMA observations make this method computationally expensive because many high resolution images must be generated and Fourier transformed. Most circumstellar disks are axisymmetric, so here a method that avoids generating images and instead models radial profiles is outlined. The two main elements are i) u, v space visibility averaging, and ii) using the Discrete Hankel Transform to convert arbitrary parametric radial surface brightness profiles to visibilities. Vertical scale height can be included, but is fixed with radius; in principle this is a limitation but in practise radially-dependent vertical structure information is beyond even ALMA’s capability for all but a few debris disks. Combined, these ingredients yield a method that is one to two orders of magnitude faster than image based methods and can be run on a laptop, is sufficient for most ALMA observations of debris disks, and can be used with gradient-based fitting methods such as Hamiltonian Monte-Carlo. A small software package is provided, which is dubbed vis-r.
Septic pulmonary embolism associated with Staphylococcus aureus: case series and review of the literature
Authors: Ünal Asena , Özdemir Ulaş , Tapaç Nisanur , Kılınç Fatma , Bakanoğlu Emel , Çetin Fatma Tuğba , Kılıç Çil Merve , Çay Ümmühan , Özgür Gündeşlioğlu Özlem , Yıldızdaş Rıza Dinçer , Çelik Ümit , Alabaz Derya
Published: February 2025

Septic pulmonary embolism (SPE) is a rare, life-threatening disease in children. We assessed the clinical, microbiological, radiological, and treatment results of patients who developed SPE due to Staphylococcus aureus (S. aureus). We retrospectively reviewed the medical records of patients with SPE associated with S. aureus between 2012 and 2023. Six patients were included in the study; the median age was 13 years (range: 9–16 years), and four (66.7%) of them were boys. At admission, the most common complaints were chest pain (83.3%), respiratory distress (83.3%), limb swelling (83.3%), limitation of movement in the extremities (83.3%), fever (50%), fatigue (50%), and cough (16.7%). Extrapulmonary septic foci were identified as follows: septic arthritis in four patients (66.7%), soft tissue infection in one patient (16.7%), and deep vein thrombosis in one patient (16.7%). Methicillin-resistant S. aureus was the most common causative pathogen (66.7%) and methicillin-susceptible S. aureus was found in 33% of patients. The median length of hospital stay was 43.5 days (range: 25-45 days). Three (50%) patients required intensive care, and one required mechanical ventilation support. No mortality was observed. In our study, the clinical and radiological features of staphylococcal SPE in children were nonspecific, similar to the literature. Although no mortality was observed in our study, previous studies have reported mortality rates of up to 11.8% in children with SPE. Early diagnosis, appropriate antibiotic treatment, and respiratory support are important in patients with SPE, especially in low-income settings where timely access to healthcare and diagnostic resources may be limited.
Firm-Level Adaptation to Climate Change in Low- and Middle-Income Countries
Authors: Goicoechea Ana , Lang Megan
Published: February 2025

The effects of climate change are disproportionately concentrated in low- and middle-income countries (LMICs). Firms have incentives to adapt to climate change, but market frictions common in developing country contexts may hinder firm adaptation efforts. This paper reviews microeconomic, empirical evidence on the impacts of climate change on firms in LMICs and firm-level adaptation strategies. Current evidence highlights challenges and opportunities from climate change and suggests that firms are attempting to adapt but face barriers to full adaptation. Limited geographic coverage and a focus on short-term responses to weather rather than responses to long-term changes in climate highlight the need for further work on firm-level climate adaptation in LMICs.
Nearly a Quarter of Americans Are Underinsured
Authors: Roush Karen
Published: February 2025

And out-of-pocket spending is increasing faster than workers' wages.
Critical Care Transport Nursing
Authors: Vest Jason C.
Published: February 2025

Transporting critically ill patients while providing ICU-level care
To Address the Nursing Faculty Shortage, Start with the Salary Gap
Authors: Christianson Jacqueline , Schindler Christine , Grabert Lisa
Published: February 2025

Nurses must advocate with policymakers for meaningful change.
Posterior Plating versus Anterior to Posterior Screws in Fixation of Posterior Column in Pilon Fractures
Authors: Baraka Mostafa M. , Fayyad Tamer A. , Thakeb Mootaz F. , Lamei Mina A. , Al Kersh Mohamed A.
Published: February 2025

Objectives:

To compare the results of anterior to posterior screws (AP screws) versus posterior buttress plating in the fixation of posterior columns fractures in pilon injuries, regarding the 1) functional and 2) radiological outcomes and 3) the incidence of complications.

Methods:

Design: Prospective, randomized clinical trial.

Setting:

Single Center, Level 1 trauma Center.

Patient Selection criteria:

All patients with two, three and four column fracture according to the four-column classification (OTA/AO 43-C1 and 43-C2) during the study period were eligible for inclusion. Patients were randomized into two groups: direct reduction and fixation by posterior buttress plating (group A) and indirect reduction with fixation by AP screws (group B). Exclusion criteria included pediatric age group with open physis, pathological fractures, open fractures and fractures with neurovascular injuries. The minimum follow up period was 24 months.

Outcome Measures and Comparisons:

The primary outcome was the quality of reduction as evaluated using postoperative plain radiographs and computed tomography (CT). Secondary outcomes included the functional American Orthopaedic Foot and Ankle Society (AOFAS) score and the incidence of complications.

Results:

30 patients were included, 15 patients were randomized to group A (mean age 42.3 (range 19-65) and 15 patients in group B (mean age 38.0 in group B (range 23-58). The mean follow up was 32 months (24-45 months). Anatomical reduction was achieved in 80% and 26.7% of group A and group B respectively. AOFAS score was significantly higher in group A compared to group B (p=0.03). There was no statistically significant difference between the two groups regarding the time to union and the complication rates (p>0.05).

Conclusions:

A higher percentage of anatomical reduction was associated with direct reduction and posterior buttress plating compared to indirect reduction and anterior to posterior screws. This was reflected by a significantly higher AOFAS score.
Heart Rate Index—An Alternative Exercise-Based Equation for Estimating Peak VO2
Authors: Wicks John R. , Oldridge Neil B. , Franklin Barry A.
Published: February 2025

Purpose:

Heart rate (HR)-derived variables (HR reserve [HRpeak − HRrest], chronotropic indices [attenuated HR response to exercise], HR recovery [attenuated HR response to exercise recovery], and peak HR index [HRpeak/HRrest]) together with peak oxygen uptake (VO2peak) are potential prognostic variables for cardiovascular and all-cause mortality. However, heart rate index (HRI) has not been established as a surrogate for VO2peak, whether measured (Meas) or estimated (Est), during cycle ergometry (CE) and/or treadmill testing (TT).

Methods:

HR-derived prognostic variables to assess cardiovascular outcomes were identified from 150 studies obtained from MEDLINE and Google Scholar searches. The Meas CE/TT-VO2peak was reported in 81 studies (21 773 participants) and Est CE/TT-VO2peak in 69 studies (331 435 participants). Using the HRI equation with metabolic equivalent (METs) = 6 × HRI − 5 (where HRI = peak HR/resting HR), HRI-VO2peak was calculated from HR data reported in the 150 studies. The HRI-VO2peak was then compared against group mean data for both Meas CE/TT-VO2peak and Est CE/TT-VO2peak.

Results:

The difference between Meas CE/TT-VO2peak and HRI-VO2peak was 1% (7.15 ± 3.25 METs vs 7.08 ± 3.02 METs [P = .833], respectively). By comparison, the difference between Est CE/TT-VO2peak and HRI-VO2peak was 25.6% (8.94 ± 2.36 METs vs 7.12 ± 2.27 METs [P < .001], respectively). Moreover, HRI equation estimation of VO2peak showed greater overprediction for TT, 26.6%, than for CE, 11.9%.

Conclusions:

The Meas-VO2peak and HRI-VO2peak agreed closely. When compared with HRI-VO2peak, Est-VO2peak from currently used exercise-based equations shows significant overprediction. Use of HRI and/or Fitness Registry and the Importance of Exercise National Database (FRIEND) registry equations warrant consideration for more accurately estimating VO2peak.
Development of the European Society of Hypertension guidelines for the management of arterial hypertension: comparison of the helpfulness of ESH 2013, 2018, and 2023 guidelines
Authors: Koller Akos , Járai Zoltán , Takács Johanna
Published: February 2025

Objective:

Over the last decade, the European Society of Hypertension (ESH) published several guidelines (GLs) for the Management of Arterial Hypertension (2013, 2018, and 2023). We hypothesized that the GL has been improved because of the publications of new evidence. Thus, we aimed to examine the development of ESH guidelines (ESH GLs) by comparing their helpfulness regarding the diagnosis and treatment of hypertension.

Methods:

A novel mathematical analysis was used to compare ESH GLs. Not only the frequency of Classes of Recommendations (CLASS) and the Levels of Evidence (LEVEL) were examined but a newly developed certainty index (CI) was calculated. This CI allows the CLASS and LEVEL to be assessed together, providing a less biased assessment of GLs, than examining the CLASS and LEVEL independently or related to each other.

Results:

The number of recommendations showed continuous and significant increases from 2013 (N = 110) to 2018 (N = 169), and 2023 (N = 269). Examining the frequency of CLASS and/or LEVEL led to biased results, showing both improvements and/or worsening comparing years. However, based on the new analysis, a continuous improvement was shown in the percentage of certainty from 2013 to 2023 (2013: 60.5%, 2018: 72.1%, 2023: 75.3%). Accordingly, the CI was also significantly increased from 2013 (CI: 0.21), to 2018 (CI: 0.44), and to 2023 (CI: 0.51).

Conclusion:

The analysis shows that compared to previous GLs, the structure of the ESH 2023 GL has been rearranged and simplified. The higher number of Recommendations indicates a continuously accumulating knowledge regarding the mechanisms, clinical findings, and epidemiology of hypertension. Moreover, the ESH 2023 GL shows a higher degree of certainty and CI, corresponding to a higher level of helpfulness of the ESH 2023 GL for healthcare professionals to diagnose, prevent, and treat hypertension.
Cannabis and liver transplant in the era of legalization: Effects of pre-transplant cannabis use on postoperative opioid use and transplant outcomes
Authors: Runge Ava , Loeb Becca , Shui Amy M. , Fenton Cynthia , Lai Jennifer , Rubin Jessica
Published: February 2025

Background:

Cannabis use is increasing in the United States, including among liver transplant candidates. Although the anesthesia literature suggests an association between cannabis use and increased post-operative pain, the impact of cannabis use on post-liver transplant (LT) opioid use remains unknown. This study investigates changes in cannabis use at a transplant center over time, as well as the impact of cannabis use on post-LT opioid use, healthcare utilization, and mortality.

Methods:

We included 4,236 patients evaluated for LT at our institution between January 2013 and July 2023. Our primary risk factor was cannabis use, defined as urine toxicology (UTox) positive for cannabis within 90 days of LT evaluation. Our primary outcome was post-LT opioid use, including oral morphine equivalents (OME) received during the LT hospitalization and discharge opioid prescriptions. We used multivariable logistic and quantile regression to compare post-LT opioid use, healthcare utilization outcomes, and mortality between cannabis users and nonusers.

Results:

Cannabis use was associated with higher OME use in the 48 hours post-LT (p=0.04). There were no statistically significant differences between groups in 72-hour (p=0.07) or 7-day cumulative OME (p=0.33), opioid prescriptions on discharge (p=0.25), hospital length of stay (LOS, p=0.69), intensive care unit LOS (p=0.94), 90-day readmission (p=0.66), or 90-day mortality (p=0.96).

Conclusions:

While cannabis use pre-LT was associated with significantly higher opioid use in the immediate postoperative period, this did not translate to differences in opioid use beyond 48 hours post-LT, or short-term healthcare utilization or clinical outcomes. These findings should help set provider expectations for immediate post-LT pain control. Our findings support the growing body of literature that fails to identify an association between pre-LT cannabis use and post-LT outcomes.
Parallel Venvovenous Extracorporeal Membrane Oxygenation Circuits During Bridge-to-Lung Transplantation
Authors: Doko Donias , Creel-Bulos Christina , Collins Keely , Miller Casey Frost , Morris Melissa , Javidfar Jeffrey , Chan Josh , Daneshmand Mani , Jabaley Craig S. , Dave Sagar B.
Published: February 2025

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) supports end-organ oxygen delivery in patients with refractory respiratory failure. Physical therapy (PT) while on ECMO provides conceptual benefits of strength and conditioning. Physical therapy can additionally be used to facilitate improvements in functional status of pulmonary reserve while VV ECMO is used to bridge to lung transplant or recovery. We report the case of a patient initially supported with VV ECMO that due to a course complicated by refractory hypoxia, cardiac arrest, and cardiogenic shock, was successfully supported with parallel, independent VV ECMO circuits, allowing for ongoing PT, to bridge to lung transplant, decannulation, and hospital discharge.
The Impact of Preoperative Right Ventricular Dysfunction and Ventricular Arrhythmias on Left Ventricular Assist Device Outcomes
Authors: Hall Douglas , Chhana Rahul A. , Yang Bin Q. , Deych Elena , Sparrow Christopher T. , Rao Praveen , Nassif Michael E. , LaRue Shane J. , Schilling Joel D.
Published: February 2025

Ventricular arrhythmias (VA) are common in patients being evaluated for left ventricular assist devices (LVADs) but the impact of comorbid right ventricular dysfunction (RVD) on outcomes after LVAD is not known. We performed a single-center, retrospective cohort study of patients undergoing LVAD implantation from 2005 to 2021. Patients were stratified by VA history before LVAD into no VA, low burden VA (LBVA), or clinically significant VA (CSVA) groups. Right ventricular function was assessed by baseline echo. Time-to-event analyses were used with a primary outcome of all-cause mortality. Secondary outcomes were implantable cardioverter-defibrillator (ICD) shock, rehospitalization, and postoperative complications related to RV failure. A total of 761 patients were included, of which 442 (58%) had no VA, 120 (16%) had LBVA, and 199 (26%) had CSVA. The mean age was 57 and 584 (77%) of patients were male. Within the CSVA group, mortality was higher in those with baseline RVD (hazard ratio [HR] = 1.6, confidence interval [CI] = 1.1–2.5). Clinically significant VA and renal dysfunction were associated with mortality on Cox proportional hazards modeling. Implantable cardioverter-defibrillator shocks after LVAD were more common in those with LBVA or CSVA. There was no difference in 6-month rehospitalization between groups. Patients with a history of CSVA undergoing LVAD implantation are at increased risk for mortality and this risk is predominantly seen in those with comorbid RVD.
Current situation of pediatric cystic fibrosis-related liver disease: results of a Spanish nationwide study
Authors: Vicente-Santamaría Saioa , Tabares-González Ana , Gascón-Galindo Celia , Tutau-Gómez Carlos , Álvarez-Beltrán Marina , Muñoz-Codoceo Rosa Ana , Rubio-Murillo María , De-Los-Santos Marianela , Salcedo-Lobato Enrique , Masip-Simó Etna , García-Romero Ruth , Fernández-Lorenzo Ana Estefanía , Moreno-Álvarez Ana , Serrano-Nieto Juliana , Hierro-Llanillo Loreto , Loverdos-Eseverri Inés , Crehuá-Gaudiza Elena , Juste-Ruiz Mercedes , Blitz-Castro Enrique , Morales-Tirado Ana , López-Cárdenes Concepción Marina , Bousoño-García Carlos , González-Jiménez David ,   on behalf of Cystic Fibrosis working group from Spanish Society of Gastroenterology, Hepatology and Pediatric Nutrition (SEGHNP)
Published: February 2025

Background

Cystic fibrosis-related liver disease (CFRLD) is a health problem that can affect as many as 30–40% of cystic fibrosis patients by the age of 12 years. We studied the epidemiology of CFRLD thanks to the first exclusively pediatric CFRLD patient registry to date.

Methods

Descriptive cross-sectional study. Information from medical records from January 2018 to December 2020 is collected. CFRLD was classified according to the European Society of Paediatric Gastroenterology, Hepatology and Nutrition 2017 criteria.

Results

Data were collected from 168 pediatric patients diagnosed with CFRLD (90.5% liver involvement without cirrhosis and 8.5% multinodular cirrhosis).

Conclusion

In this national registry, including exclusively pediatric population, liver disease is diagnosed around 7 years of age. Liver involvement without cirrhosis is the most frequent finding among our patients but about 9% of the patients already had cirrhosis. CFRLD is one of the challenges faced by pediatric gastroenterologists in the future and national registries give us the opportunity to further study and broaden our knowledge.
Plasma microRNA-30a expression in patients with chronic hepatitis B and its application value in the assessment of the severity of liver fibrosis
Authors: He Qiufeng , Chen Zhili , Deng Yang , Mao Chuangjie
Published: February 2025

Objective

The severity of liver fibrosis (LF) in chronic hepatitis B (CHB) affects the outcome and treatment. We probed plasma miR-30a expression in CHB patients and its value in assessing LF severity.

Methods

This retrospective study included 160 CHB patients and another 98 controls. Levels of lipid parameters, liver function parameters, hemoglobin, and alpha-fetoprotein were quantified by ELISA and chemiluminescence immunoassay. White blood cell, platelet, and red blood cell counts were determined using an automatic hematology analyzer. Fibrosis index based on four factors (FIB-4) was calculated. miR-30a level was determined, followed by the analysis of correlations of miR-30a expression with LF classification or with FIB-4 in CHB patients. The diagnostic value of plasma miR-30a for mild-to-moderate and severe LF in CHB patients was analyzed by receiver operating characteristic (ROC) curve.

Results

Plasma miR-30a was poorly expressed in CHB patients and decreased dependently with LF aggravation. miR-30a was negatively interrelated with LF classification and FIB-4. Plasma miR-30a had high diagnostic value for mild-to-moderate LF in CHB patients [area under the ROC curve (AUC) = 0.775, cutoff value = 0.71, 95% confidence interval (CI) = 0.685–0.849]. Plasma miR-30a had high diagnostic value for severe LF in CHB patients (AUC = 0.873, cutoff value = 0.49, 95% CI = 0.804–0.924).

Conclusion

Plasma miR-30a was weakly expressed in CHB patients. miR-30a expression was negatively correlated with LF severity in CHB patients. miR-30a had high diagnostic value for mild-to-moderate and severe LF in CHB patients. miR-30a might serve as a promising target for LF treatment.
Leveraging the gut microbiome to understand the risk factor of cognitive impairment in patients with liver cirrhosis
Authors: Li Shuyao , Niu Xiao-Xia , Liu Jia-Liang , Su Min , Li Qian-Qian , Wang Chun-Yan , Wang Jian-Jun , Chen Hong-Yan , Ji Dong
Published: February 2025

Objectives

The role of the gut-liver axis in liver cirrhosis is becoming increasingly recognized. We investigated the fecal microbiome in patients with liver cirrhosis and its potential function as a predictive biomarker of hepatic encephalopathy.

Methods

Patients were divided into either a high plasma ammonia (HPA) group or a low plasma ammonia (LPA) group according to the upper limit of normal of plasma ammonia concentration. 16S rRNA sequencing of fecal samples was performed to study how the microbiota affects the clinical symptoms of liver cirrhosis. The Stroop test was used to assess the ability of the brain to inhibit habitual behaviors.

Results

Totally, 21 subjects were enrolled. Among the 18 patients with liver cirrhosis, 14 were male, the age range was 42–56 years, and the plasma ammonia level range was 20–125.9 μmol/l. The Stroop test showed more severe cognitive impairment in HPA than in LPA individuals. At the same time, there were significant differences in fecal microbiome characteristics between the two groups, characterized by a further increase in the abundance of the Proteobacteria phylum in the gut (especially aerobic Enterobacteriaceae). Function predictions of Phylogenetic Investigation of Communities by Reconstruction of Unobserved States in the microbiome further explained the increase in the Enterobacteriaceae-dominated polyamine synthesis pathway in the gut microbiome of HPA groups.

Conclusion

Cirrhotic patients with hyperammonemia have a specific fecal bacterial composition (characterized via expansion of Enterobacteriaceae). The ability to bio-synthesize polyamines that Enterobacteriaceae possesses is likely to be a key factor in the elevation of plasma ammonia.
All hands on deck
Authors: Reed Sokonie , Hermann Maureen
Published: February 2025

There exists a lack of emphasis on community and public health in nursing school. New approaches like the use of guest speakers and targeted classroom activities may bridge this gap.
Preschool children with insufficient physiological hyperopia experience accelerated myopic drift
Authors: Bian Shimeng , Pu Jianing , Chen Wei , Zhou Zhen , Zhang Ranran , Wang Dan , Mi Xuejing , Yang Yanyan , Peng Chuzhi , Xu Huaying , Jin Mingrui , Jiao Yonghong
Published: February 2025

SIGNIFICANCE

This study reveals that preschool children with insufficient physiological hyperopia experience accelerated myopic drift and axial length elongation. Regular monitoring can serve as an early warning for impending myopia during early childhood, highlighting its critical role in future myopia prevention strategies.

PURPOSE

This study examines the patterns of spherical equivalent and biometric parameters if physiological hyperopia has shown an accelerated tendency to regress by preschool age and whether the early onset of physiological hyperopia regression accelerates myopia onset.

METHODS

This kindergarten-based longitudinal observational study included 1308 children between 3 and 6 years old from kindergartens in Haidian District, Beijing, China. Comprehensive eye examinations were performed on all participants.

RESULTS

Two grouping methods were used for all children. The first was based on their baseline age and divided into four groups of 3 to 6 years. The second was based on spherical equivalent, with spherical equivalent >0.75 D designated as the physiological hyperopia group and spherical equivalent ≤+0.75 D designated as the pre-myopia or myopia group. Physiological hyperopia and the proportion of children with physiological hyperopia displayed a declining trend over time in all age groups (p<0.001), with the older the baseline age, the more pronounced the decline (p<0.001), and the rate increased year by year (p<0.001). In contrast, axial length, anterior chamber depth, and axial length/corneal curvature radius displayed an increasing trend (p<0.001), and the rate of increase of axial length and anterior chamber depth accelerated over time (p<0.001). Female children have more physiological hyperopia and a higher proportion of children with physiological hyperopia compared with males (p<0.001) but displayed a more rapid decline (p<0.001). The axial length, anterior chamber depth, and the axial length/curvature radius were found to be elevated in the pre-myopia or myopia group in comparison to the physiological hyperopia group (p<0.001). Furthermore, the magnitude of the rate increase in myopic drift and axial length was found to be greater in the aforementioned group.

CONCLUSIONS

The regression of physiological hyperopia accelerates in preschool-age children, with older children showing faster regression and lower levels of physiological hyperopia. This premature decline correlates with an increased rate of myopic drift and accelerated biometric growth. Therefore, regular monitoring of physiological hyperopia should begin at preschool age, as the rate of regression serves as a more reliable predictor of future myopia than refraction alone.
Insights into the Clinical Prognosis of High-grade Appendiceal Mucinous Neoplasms
Authors: Dartigues Peggy , Kepenekian Vahan , Illac-Vauquelin Claire , Verriele Véronique , Fontaine Juliette , Isaac Sylvie , Chevallier Anne , Valmary-Degano Séverine , Laverriere Marie-Hélène , Avérous Gerlinde , Bibeau Frédéric , Villeneuve Laurent , Glehen Olivier , Benzerdjeb Nazim ,   on behalf of the RENAPE Network
Published: February 2025

High-grade appendiceal mucinous neoplasm (HAMN) is used to describe a rare epithelial neoplasm of the appendix characterized by pushing-type invasion and high-grade cytologic atypia. Its implications regarding lymph node spread and the necessity of right colectomy are currently debate. The objective of the present study was to assess the clinicopathologic characteristics, the risk of lymph node and peritoneal metastasis, and long-term outcomes of patients diagnosed as HAMN in comparison to low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma, treated by right hemicolectomy. A total of 443 patients diagnosed with LAMN (n=246), HAMN (n=34), or appendiceal adenocarcinoma (n=163) and who underwent right colectomy with lymph node dissection in all cases within 32 institutions of the French Network for Rare Peritoneal Malignancies (RENAPE) were included. The median age was 56.5 years (range: 21 to 91), and the majority were female (n=250, 56.4%) without difference between groups (P=0.604). Lymph node metastases were identified in 17.8% of appendiceal adenocarcinoma cases (29/163); none were found among LAMN or HAMN cases. A higher number of lymph nodes were analyzed in those treated for appendiceal adenocarcinoma than LAMN (P<0.001) and HAMN (P=0.035). Regarding peritoneal metastasis, a higher proportion of cases were classified as high-grade with/without signet cells in patients treated for HAMN (P<0.001) and appendiceal adenocarcinoma (P<0.001) than those treated for LAMN. Among patients with perforation of the appendix, those treated for LAMN had longer overall survival (OS; P<0.001) and progression-free survival (PFS; P<0.0001) than those treated for appendiceal adenocarcinoma or those treated for HAMN; among patients without perforation, those treated for LAMN and HAMN had longer OS (P=0.042) and PFS (P=0.012) than those treated for appendiceal adenocarcinoma. No lymph node metastases were observed in patients treated for HAMN, and those without appendix perforation had a similar prognosis to LAMN. This study supports staging HAMN using the same system as LAMN and treating it with appendectomy alone in the absence of appendix perforation.
P2Y12-mediated HIV gp120 and ddC-induced neuropathic pain improved by esculin
Authors: Yi Zhihua , Si Han , Liang Shangdong , Li Guilin , Dang Yifan , Zhou Congfa
Published: February 2025

We studied whether esculin (ES) has the effect of alleviating peripheral neuropathic pain (NP) in rat models of HIV glycoprotein 120 (gp120) together with zalcitabine (2’,3’-dideoxycytidine; ddC) treatment and explored the possible mechanism of it. The rats pain behaviors were evaluated by observing the paw withdrawal threshold (PWT) and the paw withdrawal latency (PWL). The rats were divided into a control group, sham group, gp120 combined with a ddC treatment group (gp120& ddC group), gp120&ddC combined with ES treatment group (gp120&ddC+ES group), which ES was administered intragastrically, and gp120&ddC combined with short hair RNA of P2Y12 receptor (rP2Y12) treatment group (gp120&ddC+shP2Y12 group), which shRNA of rP2Y12 was injected intrathecally with a dose of 25 µg/20 µl for every rat, and a negative control plasmid was administered to the gp120&ddC+nc group. Western blotting was used to measure the protein expression levels of the rP2Y12, the nuclear factor of activated T-cells type c1 (NFATc1), phospho-NFATc1 and the C-C motif chemokine ligand 3 (CCL3) in the L4–L6 dorsal root ganglia (DRG). Real-time quantitative PCR (RT-qPCR) was used to test the mRNA expression level of the CCL3. Double-labeling immunofluorescence was used to identify the co-localization of the rP2Y12 with glial fibrillary acidic protein (GFAP) in DRG. Fluorescence imaging with calcium indicator fluo-3 AM (7.5 μM) was performed to observe the change of intracellular calcium concentration ([Ca2+]i). Molecular docking was performed to identify the interaction between rP2Y12 and the ligand ES. We found that accompanied by the attenuation of mechanical allodynia and thermal hyperalgesia, rP2Y12 expression in the gp120+ddC+ES group of rats was downregulated compared with the gp120+ddC ones, as was the coexpression of the rP2Y12 and GFAP of satellite glial cells (SGCs) in DRG, and the CCL3 mRNA levels and protein expression were both decreased. In addition, mechanistic studies have found that there is a docking pocket between ES and the rP2Y12 protein, which causes ES to decrease the [Ca2+]i, thus increasing the phosphorylation level of NFATc1. Taken together, the results suggest that ES can combine with the rP2Y12, inhibit DRG SGCs activation caused by gp120&ddC, reduce [Ca2+]i, and prevent the NFATc1-mediated gene transcription of CCL3, finally relieving NP in rats treated with gp120&ddC.
Gamma-aminobutyric acid and glutamate/glutamine associations with tinnitus and hearing loss
Authors: Khan Rafay Ali , Wang Zepeng , Zhao Ruiyang , Kim Gibbeum , Lam Fan , Husain Fatima Tazeena
Published: February 2025

The present study aimed to evaluate the association between concentrations of the metabolites gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx), which have predominantly inhibitory and excitatory effects on neural function, respectively, in adults with tinnitus and hearing loss, those with only hearing loss, and controls with neither condition. Metabolite concentrations in all three participant groups were assessed via magnetic resonance spectroscopic imaging in auditory and fronto-parietal regions. The concentration of a third metabolite, creatine (Cre) was also acquired. Ratios of GABA/Cre, Glx/Cre, and Glx/GABA were compared across six manually delineated regions of interest (ROIs). Neither GABA/Cre nor Glx/Cre showed significant group differences in any of the six ROIs. For the Glx/GABA ratio, group-level differences were seen only in the right auditory cortex, where the control group had a significantly larger ratio than the group with tinnitus and hearing loss. While results largely did not replicate previous human work in this area, we cannot exclude the possibility of a neurochemical mechanism underlying any causal relationship between hearing loss and tinnitus, particularly given the finding of altered balance in excitatory/inhibitory metabolites in the right auditory cortex. In the context of previous work, the right auditory cortex is highlighted as a particular region of interest for further investigation. Methodological differences in human studies and inconsistent findings in animal studies have thus far impeded the field’s ability to gain direct insight into the relationship between tinnitus and hearing loss, and so we make some suggestions to help design future studies.
A Bayesian phylodynamic inference framework for single-cell CRISPR/Cas9 lineage tracing barcode data with dependent target sites
Authors: Zwaans A. , Seidel S. , Manceau M. , Stadler T.
Published: February 2025

Analysing single-cell lineage relationships of an organism is crucial towards understanding the fundamental cellular dynamics that drive development. Clustered regularly interspaced short palindromic repeats (CRISPR)-based dynamic lineage tracing relies on recent advances in genome editing and sequencing technologies to generate inheritable, evolving genetic barcode sequences that enable reconstruction of such cell lineage trees, also referred to as phylogenetic trees. Recent work generated custom computational strategies to produce robust tree estimates from such data. We further capitalize on these advancements and introduce GESTALT analysis using Bayesian inference (GABI), which extends the analysis of genome editing of synthetic target arrays for lineage tracing (GESTALT) data to a fully integrated Bayesian phylogenetic inference framework in software BEAST 2. This implementation allows users to represent the uncertainty in reconstructed trees and enables their scaling in absolute time. Furthermore, based on such time-scaled lineage trees, the underlying processes of growth, differentiation and apoptosis are quantified through so-called phylodynamic inference, typically relying on a birth–death or coalescent model. After validating its implementation, we demonstrate that our methodology results in robust estimates of growth dynamics characteristic of early
Danio rerio
development. GABI’s codebase is publicly available at
https://github.com/azwaans/GABI
.

This article is part of the theme issue ‘“A mathematical theory of evolution”: phylogenetic models dating back 100 years’.
Decoding non-human mammalian adaptive signatures of 2.3.4.4b H5N1 to assess its human adaptive potential
Authors: Nataraj Ranjana , Ashok Avinash Karkada , Dey Ayushi Amin , Kesavardhana Sannula
Published: February 2025

The recent panzootic 2.3.4.4b clade H5N1 infected diverse non-human mammalian species globally, showed mammal-to-mammal transmission among them and caused sporadic human infections. However, whether 2.3.4.4b H5N1 circulating in non-human mammals can establish human infections and spread among humans is unclear. Gain-of-function research restrictions preclude assessing human adapting mutations of 2.3.4.4b H5N1. Here, we tracked the evolution of 2.3.4.4b H5N1 that infected non-human mammals and evaluated their ability to gain human adaptations. The non-human mammal 2.3.4.4b H5N1 partly acquired classical human adapting mutations, which are identical to the residues of H1N1pdm09 and seasonal human H3N2 infections while showing a few species-specific adaptations that might be potential barriers for successful human adaptations. Despite minimal changes in Hemagglutinin (HA), A160T and T199I mutations near the receptor binding site of HA in dairy cattle viruses indicate the rapid HA glycan surface evolution affecting virus entry and immune evasion. The quantitative assessment indicated that 2.3.4.4b H5N1 circulating in bears, cattle, dolphins, and foxes show higher human adaptive potential than other hosts. Also, H5N1 infections in mammals across time showed a unique set of adaptations in the 2.3.4.4b clade compared to previously circulating strains, especially the acquisition of Q591 adaptation in PB2 that enables human adaptation. Thus, 2.3.4.4b H5N1 acquires human adaptations due to natural selection pressure in non-human mammals. Overall, our study delineates human adaptation and infection risk of specific non-human mammalian circulating HPAI 2.3.4.4b H5N1 strains.

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Women’s empowerment and life stage: assessing intersectional differences in contraceptive method mix in sub-Saharan Africa
Authors: Hellwig Franciele , Wado Yohannes Dibaba , Faye Cheikh M , Requejo Jennifer , Alkema Leontine , Kananura Rornald Muhumuza , Boerma Ties , Barros Aluísio JD
Published: February 2025

Background

Women’s empowerment positively impacts family planning in sub-Saharan Africa, but little is known about its relationship with contraceptive method mix. Considering that contraceptive needs vary across life stages, we aimed to explore the intersectional differences in contraceptive method mix according to age and level of empowerment in sub-Saharan Africa.

Methods

We analyzed data from Demographic and Health Surveys conducted from 2015 to 2022 across 28 countries in West & Central and Eastern & Southern Africa. Within each region, we calculated pooled estimates of demand for family planning satisfied by any method (DFPS) and contraceptive method mix, stratifying by women’s age and empowerment level according to the SWPER Global index.

Results

Our sample included 138,374 married women of reproductive age. Across both regions, DFPS increased with empowerment, especially among women older than 19. Among adolescents, a substantial increase was only identified in terms of decision-making. Contraceptive method mix was skewed towards injectables and implants, but their shares dropped as empowerment increased. This trend appeared across all age groups and empowerment domains, with the largest declines observed for social independence. High-empowered women had a more diversified method mix, with adolescents and young women showing increased use of condoms, pills, and fertility-awareness methods, while women over 34 relied more on IUDs and sterilization.

Conclusion

Our findings reveal that age, empowerment, and contraceptive method mix intersect in diverse ways. Tailoring family planning policies and counseling while addressing empowerment drivers could enhance informed contraceptive choices and better meet women’s reproductive health goals.
Random patterns of medicinal plants on a phylogeny do not imply random selections of medicinal plants
Authors: Yessoufou Kowiyou , Yaradua Samaila Samaila , Gaoue Orou G.
Published: February 2025

Existing studies report that medicinal plants are either phylogenetically clustered or that plant medicinal property is phylogenetically conserved. Each scenario is traditionally interpreted as evidence of non-random selection, by humans, of medicinal plants. Here, we argue that this interpretation is misleading arguing that both scenarios are simultaneously required for a correct interpretation of human selection of medicinal plants, and we propose a framework to illustrate all possible scenarios of phylogenetic patterns and human selection options.

To demonstrate the use of this framework, we conducted a survey across Katsina State in northern Nigeria, West Africa, to record plants used to treat various ailments and then employed phylogenetic comparative methods to investigate the basis for integrating a given plant in the regional pharmacopoeia.

First, we found a mixed selection pattern in organs used for medicine, perhaps mirroring the within-plants heterogeneous distribution of secondary compounds as predicted in the optimal defense theory. Second, medicinal plants used to treat most diseases follow a random distribution on the phylogeny whereas their medicinal property is convergent on the phylogeny. This pattern is plausible only when humans select preferentially less-related species for medicinal uses.

That we found a random phylogenetic structure for species used to treat most diseases would, traditionally, have been interpreted as random selections of medicinal plants. We therefore call for caution and the use of the framework we propose while interpreting phylogenetic patterns in ethnobiology.

Societal Impact Statement

Plants are sources of modern drugs, and traditionally used plants for medicine are the first target in bio-screening. Early discussions suggest that humans randomly select plants that they use medicinally. However, recent studies demonstrate a rather nonrandom selection pattern. Here, we argue that the conclusion of nonrandom selection is grounded on less accurate interpretation of phylogenetic patterns. We consequently propose a framework with which to interpret medicinal plant selection by human and demonstrate, using data from Nigeria in West Africa, how this framework can be used.
Effects of Pesticide Exposure on Neuroinflammation and Microglial Gene Expression: Relevance to Mechanisms of Alzheimer’s Disease Risk
Authors: Mhatre-Winters Isha , Eid Aseel , Blum Nicole , Han Yoonhee , Sammoura Ferass M. , Wu Long-Jun , Richardson Jason R.
Published: February 2025

Background

Alzheimer’s disease (AD) is characterized by the presence of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Previously, we reported serum levels of dichlorodiphenyldichloroethylene (DDE), the primary metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were significantly higher in AD patients compared to age-matched controls and that DDT exposure worsened AD pathology in animal models.

Objective

Here, we investigated the effect of DDT on neuroinflammation in primary mouse microglia (PMG) and C57BL/6J mice.

Methods

Effects of DDT on inflammation and disease-associated microglia were determined in primary mouse microglia and C57BL/6J mice.

Results

PMG exposed to DDT (0.5-5.0 µM) elicited a ∼2-3-fold increase inIl-1bmRNA levels, with similar concentration-dependent upregulation inIl-6, Nos2,andTnfa. These effects were blocked by the sodium channel antagonist tetrodotoxin, demonstrating the role of DDT-microglial sodium channel interactions in mediating this response. Additionally, NOS2 protein levels increased by ∼1.5-2-fold, while TNFa was elevated by 2-4-fold. C57BL/6J male and female mice exposed to DDT (30 mg/kg) demonstrated significantly increased mRNA levels ofNos2,Il-1b, andIl-6in the frontal cortex (1.5-2.3-fold), andNos2,Il-1b,andTnfa(1.5-1.8-fold) in the hippocampus. Furthermore, microglial homeostatic genes,Cx3cr1,P2ry12,andTmem119, were downregulated, while stage 1 disease-associated microglia genes were upregulated bothin vitroandin vivo. Notably,ApoeandTrem2were only upregulated in the frontal cortex and hippocampus of females.

Conclusion

These data indicate that DDT increases neuroinflammation, which may result from direct actions of DDT on microglia, providing a novel pathway by which DDT may contribute to AD risk.