bluuebunny/crossref_metadata_2025 huggingface dataset:
Dexmedetomidine-associated hypothermia in critical trauma: A case report and literature analysis
Authors: Kim Se Heon , Sul Younghoon , Ye Jin Bong , Lee Jin Young , Lee Jin Suk
Published: January 2025

Rationale:

Hypothermia, defined as a core body temperature below 35°C, is a common and serious complication in severe trauma patients, often worsened by hemorrhage and medical interventions. Dexmedetomidine, an α2-adrenergic agonist used for sedation in intensive care units, has known thermoregulatory effects; however, its association with hypothermia in trauma patients remains insufficiently explored.

Patient concerns:

A 40-year-old male with severe polytrauma from a motor vehicle accident presented in distress, with hypotension, tachycardia, and a baseline temperature of 35.8°C. Despite effective management, he developed profound hypothermia, with a recorded temperature dropping below 34.0°C after switching from midazolam to dexmedetomidine for sedation.

Diagnoses:

The patient had multiple bilateral rib fractures, a right-sided pneumothorax, and grade 3 liver and grade 5 splenic injuries, along with orthopedic fractures. His Injury Severity Score signified critical trauma, increasing the risk of complications like hypothermia.

Interventions:

Following stabilization, dexmedetomidine was administered for sedation. Continuous warming interventions were initiated to address hypothermia; however, the temperature continued to decline. Suspecting dexmedetomidine’s contribution, its administration was discontinued.

Outcomes:

After stopping dexmedetomidine, the patient’s temperature gradually recovered to 36.8°C within 5 hours. He demonstrated improved consciousness and stable vital signs, subsequently undergoing 2 successful orthopedic surgeries and discharging without further hypothermia-related issues.

Lessons:

This case highlights dexmedetomidine’s potential to induce hypothermia in critically ill trauma patients. It stresses the importance of careful temperature monitoring and proactive thermoregulation during sedative administration in intensive care. Further research is needed to explore the prevalence and mechanisms of dexmedetomidine-associated hypothermia in trauma populations.
Lupus Nephritis Renal Response in a Real-World Setting in Argentina
Authors: Reyes Torres Alvaro Andres , Scaglioni Valeria , Soriano Enrique R. , Rosa Javier Eduardo , Scolnik Marina
Published: January 2025

Objective

To identify the percentage of patients with incident lupus nephritis who achieved primary efficacy renal response (PERR) and complete renal response (CRR) after 2 years of treatment at a university hospital.

Methods

An observational study including patients with lupus with a first renal biopsy with nephritis class III, IV, or V, or combined, performed between years 2000 and 2018 and follow-up for over 2 years at a university hospital in Argentina. The proportion of patients with PERR and CRR at 1 and 2 years and the proportion of patients requiring rescue therapy were calculated. Comparison with clinical trials and observational studies was done through literature search.

Results

Seventy-five patients were included; 85.3% were female and 36.5 years in average at the time of biopsy, with lupus nephritis class III (n = 7), class IV (n = 59), combination of IV + V (n = 4), and pure V (n = 5). At 1 and 2 years, PERR was achieved in 57 patients (76.0%; 95% confidence interval [CI], 64.8%–84.5%), whereas CRR was achieved in 44 patients (58.7%; 95% CI, 46.9%–69.4%). A proteinuria level <0.7 g/24 hours was observed in 80.0% (95% CI, 69.2%–87.7%) of patients at 2 years and <0.5 g/24 hours in 76.0% (95% CI, 64.8%–84.5%). Fifteen patients (20.0%; 95% CI, 12.3%–30.8%) needed rescue therapy during the first 2 years after biopsy.

Conclusion

We found higher PERR (76.0%) and CRR (58.7%) at 2 years after the first renal biopsy than those reported in many randomized trials, similar to those reported in observational studies.
NAT10 promotes pyroptosis and pancreatic injury of severe acute pancreatitis through ac4C modification of NLRP3
Authors: Gao Ke , Yang Xuejiao , Zhao Wei , Lin Yipeng , Hu Bin , Wang Dadong
Published: January 2025

Severe acute pancreatitis (SAP) is a highly morbid acute digestive disorder linked to pyroptosis. N-acetyltransferase 10 (NAT10) facilitates the production of N4-acetylcytidine (ac4C) modifications in mRNA, thereby contributing to the progression of various diseases. However, the specific role of NAT10 in SAP remains to be elucidated. This study aimed to elucidate the mechanism through which NAT10 mediates pyroptosis in SAP. Sprague-Dawley rats and AR42J rat pancreatic exocrine cells were used to establish in vivo and in vitro models of SAP. The levels of ac4C and NAT10 expression were quantified using dot blot analysis and quantitative real-time PCR (qPCR). Assessment of cell viability, apoptosis, amylase content, and concentrations of lactate dehydrogenase (LDH), interleukin (IL)-1β, and IL-18 was conducted to evaluate the severity of SAP both in vivo and in vitro. Pyroptosis was assessed by measuring caspase-1 and gasdermin D (GSDMD)-N-terminal (GSDMD-N) expression. Further mechanistic insights were gained using methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays. Our findings indicate that the levels of ac4C modification and NAT10 were elevated in both in vivo and in vitro SAP models. Knockdown of NAT10 inhibited cell death and reduced the levels of amylase, LDH, IL-1β, and IL-18 as well as the protein expression of caspase-1 and GSDMD-N, suggesting that NAT10 knockdown suppresses pyroptosis in SAP cell models. Mechanistically, NAT10 knockdown decreased the expression and stability of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) mRNA by inhibiting ac4C modification of NLRP3. Moreover, NAT10 knockdown alleviated pancreatic tissue pathology, mitigated SAP severity, and suppressed pyroptosis in an SAP rat model. Collectively, these results demonstrate that NAT10 exacerbates pancreatic injury in SAP by promoting pyroptosis through ac4C modification of NLRP3, thereby enhancing its expression. These findings suggest a potential novel therapeutic target for SAP.
Obstetric Anal Sphincter Injury: Vaginal Birth After Cesarean Versus First Vaginal Delivery
Authors: Mumford Brigid S. , Lemon Lara , Harris John , Giugale Lauren E.
Published: January 2025

Importance

Modern data regarding the relationship between vaginal birth after cesarean (VBAC) and obstetric anal sphincter injury (OASI) are minimal with mixed results.

Objective

The aim of the study was to determine if VBAC is associated with an increased risk of OASIs.

Study Design

This was a retrospective cohort study of liveborn deliveries from 2018 to 2022 within a large, multihospital academic health system. The primary outcome was the proportion of OASIs compared between patients who underwent a first vaginal delivery (primiparous vaginal delivery group) versus patients who underwent a first VBAC (VBAC group).

Results

A total of 17,044 patients were included. A total of 16,208 had a primiparous vaginal delivery and 836 underwent VBAC. Vaginal birth after cesarean patients were older (29.9 vs 27.0 years, P < 0.01), more likely to self-identify as Black or Asian race (26.1% vs 18.0%, P < 0.01), and had lower maternal weight (182.7 vs 187.2 lbs, P < 0.01). The proportion of OASIs was significantly higher in the VBAC group (6.9% vs 5.1%, P = 0.02). Vacuum-assisted vaginal deliveries were more common in the VBAC group (7.7% vs 5.4%, P < 0.01).

On multivariable logistic regression, VBAC was not significantly associated with OASIS (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.75–1.36, P = 0.95). Operative vaginal delivery (OR = 6.44, CI = 5.51–7.52, P < 0.01), older maternal age (OR = 1.05, CI = 1.03–1.07), and Asian race (OR 2.62, CI = 2.10–3.26) demonstrated increased odds of OASIs. Patients who identified as Black demonstrated lower odds of OASIs (OR = 0.68, CI = 0.50–0.93).

Conclusions

While there was a greater proportion of OASIs in the VBAC group compared to the primiparous vaginal delivery group, VBAC was not an independent risk factor.
External and Internal Load Profiles of Male and Female Participants during a Walking Football Practice
Authors: da Costa Julio Alejandro Henriques Castro , Pereira Catarina , Barbosa Ana , Seabra André , Brito João , Pinto Ana , Martins Catarina , Moreira Rafaela , Gonçalves Bruno
Published: January 2025

BACKGROUND: High levels of sedentary behavior among older adults highlight the importance of walking football (WF) in promoting physical activity for healthy aging. This study examines the external and internal load profiles of male and female participants during a WF tournament, addressing a gap in research on game demands and induced load. METHODS: The study involved 176 players aged 50+ participating in a 40-min, 5v5 WF tournament with unlimited substitutions. External load (total and categorized distances) was measured using Global Positioning System (GPS), while heart rate (HR) monitors assessed internal load, including absolute HR and intensity zones based on %HRmax. RESULTS: The proportion of male participants (n=123; 70.3%) was higher than females (n=52; 29.7%), p<.001. They were similar in age (61.6±8.6 and 60.8±6.9, respectively). Males covered a higher distance per minute than females, with sex showing a moderate effect (63.3±10.7 m/min vs. 54.7±15.8 m/min; p < .001; Cohen’s dunbiased = 0.69 [0.36; 1.03]), especially in fast walking (41.7±12.2 m/min vs. 32.6±16.7 m/min; p < .001; Cohen’s dunbiased = 0.66 [0.33; 1.00]). Males played more time than females (22:26±09:47 min:ss vs. 15:41±07:46 min:ss; p<.001), with moderate effect (Cohen’s dunbiased = 0.73 [0.40; 1.06]). However, no differences between sexes were identified in the internal load variables, such that the female average %HRmax was 80±11% and the male was 82±8% during the practice. CONCLUSIONS: Overall, while males generally exhibit higher external loads in WF, both sexes experience similar internal load demands, highlighting WF’s potential as a scalable, health-promoting intervention for aging populations.
The impact of physician handoffs on the outcomes of admitted emergency department patients: a medical administrative database retrospective cohort study
Authors: Mokhtari Akram , Simonyan David , Mallet Myriam , Blais S. , Moore L. , Berthelot Simon
Published: January 2025

Introduction

A physician handoff is the process through which physicians transfer the primary responsibility of a care unit. The emergency department (ED) is a fast-paced and crowded environment where the risk of information loss between shifts is significant. Yet, the impact of handoffs between emergency physicians on patient outcomes remains understudied. We performed a retrospective cohort study in the ED to determine if handed-off patients, when compared to non-handed-off patients, were at higher risk of negative outcomes.

Methods

We included every adult patient first assessed by an emergency physician and subsequently admitted to hospital in one of the five sites of the CHU de Québec-Université Laval during fiscal year 2016-17. Primary outcome was mortality. Secondary outcomes were incidence of ICU admission and surgery and hospital length of stay. We conducted propensity score based analysis accounting for patient and hospital clusters and adjusting for demographics, multiple disease severity indicators and ED processes indicators, including crowding.

Results

21,136 ED visits and 17,150 unique individuals were included in the study. Median[Q1-Q3] age, Charlson score, door-to-emergency-physician time and ED length of stay were 71[55-83] years old, 3[1-4], 48 [24,90] minutes, 20.8[9.9,32.7] hours, respectively. In propensity score analysis (OR handoff/no handoff [CI95%] or GMR[Cl95%]), handoff status was not associated with mortality (1.08[0.93,1.26]), ICU admission (1.01[0.87,1.18]) or hospital length of stay (1.02[0.94-1.10]). Sensitivity and sub-group based analyses yielded no further information.

Conclusion

Emergency physicians’ handoffs were not associated with an increase in risk of severe in-hospital adverse events. Further studies are needed to explore the impact of ED handoffs on adverse events of low and moderate severity.

What is already known on this subject

Handoffs are widely believed to affect patient outcomes in the ED, although data remains scarce.

What did this study ask

What is the impact of handoffs between emergency physicians on patient outcomes

What this study adds

Handed off patients do not seem to do worse than non handed off patients concerning majors outcomes (mortality, ICU admission, LOS).

Why does it matter to clinicians?

In the ED, handoffs may not represent a risk to patient outcomes. QI efforts may be better invested in other care inefficiencies.
OsWRKY53 dictates wound responses in rice through fine-tuning cross-talk between PEP and PSK mediated signalling
Authors: Harshith Chitthavalli Y. , Dey Riju , Palchaudhuri Dipasmit , Shivaprasad Padubidri V.
Published: January 2025

Wounding and tissue damage are major events among the multitude of stresses that plants face in their natural environment. Wound response is a very dynamic event that involves the integration of various regulatory networks culminating in successful wound-induced downstream signalling. Plants depend on endogenously derived molecular signals to initiate wound responses. Transcriptional response is paramount in dictating successful transition of early defense to late growth responses. Here we show the involvement of a WRKY transcription factor (TF) named OsWRKY53, that is responsive to both wounding as well as wound-derived plant elicitor peptide (PEP), OsPep2 treatments. OsWRKY53 is involved in positive regulation of gene expression of OsPep2 responsive genes. OsWRKY53 displays altered DNA occupancy in response to OsPep2 treatment over time correlating with the altered gene expression. Further, OsWRKY53 is involved in simultaneous activation and suppression of OsPep2-responsive and phytosulfokine (PSK) responsive genes, respectively. In agreement with these, mis-expression of OsWRKY53 led to compromised wound responses. Collectively, we establish that OsWRKY53 acts at the intersection of PEP and PSK mediated transition of wound responses and positively regulates the early defense-related gene expression.
VDR-calcium axis regulates the diet-driven metabolic shift during weaning
Authors: Jawla Neha , Khare Shubhi , Yadav Nidhi , Nanda Ranjan Kumar , Arimbasseri Gopalakrishnan Aneeshkumar
Published: January 2025

Weaning in mammals is associated with a shift in the metabolism, driven by the differences in the macronutrient composition of milk and post-weaning diet. Milk has a higher fat content compared with the carbohydrate-enriched solid food. Malnutrition during this stage could affect this transition with long-term adverse effects. The role of micronutrients during this transition is not well understood. Mice lacking a functional vitamin D receptor (VDR) progressively develop severe skeletal muscle and adipose atrophy after weaning, suggesting a role for vitamin D signaling in the metabolic transition during weaning. Here, we demonstrate that after weaning, VDR knock-out mice exhibit systemic energy deprivation and higher lipolysis in inguinal white adipose tissue, probably due to increased norepinephrine signaling via protein kinase A (PKA) and extracellular signalling-regulated kinase (ERK) pathways. Energy deprivation invdr-/-mice is associated with defective liver glycogenolysis, characterized by increased expression of protein phosphatase-1α and decreased phosphorylation of glycogen phosphorylase. However, restoration of serum calcium levels by a rescue diet is sufficient to restore energy metabolism invdr-/-mice. Interestingly, maintaining a high-fat-containing milk-based diet post-weaning could prevent the onset of energy deprivation, liver glycogen storage defect, and adipose atrophy in these mice without restoring serum calcium levels. Our data show that the vitamin D-calcium axis is essential for the adaptation of mice to the dietary shift from high-fat-containing milk to post-weaning carbohydrate-enriched diets. It also reveals a novel macronutrient-micronutrient interaction that shapes the metabolic flexibility of the individual based on the dietary composition of nutrients.
Multiple neural network approaches, including use of topological data analysis, enhances classification of human induced pluripotent stem cell colonies by treatment condition
Authors: Ruys de Perez Alexander , Anderson Paul E. , Dimitrova Elena S. , Kemp Melissa L.
Published: January 2025

Understanding how stem cells organize to form early tissue layers remains an important open question in developmental biology. Helpful in understanding this process are biomarkers or features that signal when a significant transition or decision occurs. We show such features from the spatial layout of the cells in a colony are sufficient to train neural networks to classify stem cell colonies according to differentiation protocol treatments each colony has received. We use topological data analysis to derive input information about the cells’ positions to a four-layer feedforward neural network. We find that despite the simplicity of this approach, such a network has performance similar to the traditional image classifier ResNet. We also find that network performance may reveal the time window during which differentiation occurs across multiple conditions.

Author summary

Our understanding of how stem cells determine what specialized cells to differentiate into is still incomplete. One aspect of understanding this process involves identifying when key decisions about a cell’s fate occur. We explored whether by looking at the layout of the cells of the colony, we can infer knowledge regarding the eventual phenotypes the cells are differentiating towards. We train an algorithm to recognize cell type using spatial information by taking as input the number and size of holes that appear among the colony’s cells. We find this method succeeds in its classification, similar to an industry-grade image classifier.
Advanced Manufacturing of Coil-Reinforced Multilayer Vascular Grafts to Optimize Biomechanical Performance
Authors: Robinson Andrew , Jiang David , Nkansah Abbey , Herrera Duran Juan S. , Leung Jonathan , Laude Madeline , Craig John , Guo Leopold , Timmins Lucas , Cosgriff-Hernandez Elizabeth
Published: January 2025

Small diameter vascular grafts require a complex balance of biomechanical properties to achieve target burst pressure, arterial compliance-matching, and kink resistance to prevent failure. Iterative design of our multilayer vascular was previously used to achieve high compliance while retaining the requisite burst pressure and suture retention strength for clinical use. To impart kink resistance, a custom 3D solution printer was used to add a polymeric coil to the electrospun polyurethane graft to support the graft during bending. The addition of this reinforcing coil increased kink resistance but reduced compliance. A matrix of grafts were fabricated and tested to establish key structure-property relationships between coil parameters (spacing, diameter, modulus) and biomechanical properties (compliance, kink radius). A successful graft design was identified with a compliance similar to saphenous vein grafts (4.1 ± 0.4 %/mmHgx10-2) while maintaining comparable kink resistance to grafts used currently in the clinic. To explore graft combinations that could increase graft compliance to match arterial values while retaining this kink resistance, we utilized finite element (FE) models of compliance and kink radius that simulated experimental testing. The FE-predicted graft compliance agreed well with experimental values. Although the kink model over-predicted the experimental kink radius values, key trends between graft parameters and kink resistance were reproduced. As an initial proof-of-concept, the validated models were then utilized to parse through a targeted graft design space. Although this initial parameter range tested did not yield a graft that improved upon the previous balance of graft properties, this combination of advanced manufacturing and computational framework paves the way for future model-driven design to further optimize graft performance.

TOC
Feasibility and effectiveness of a smartwatch-based intervention program for ameliorating depressive symptoms: a pilot-study
Authors: Tamm Jeanette , Brendler Andy , Bauer Anastasia , Gordon Janina , Strauss Daniela , Brinkmann Ronja , Degmayr Raphael , Pfahl Daniel , Friedrichs Markus , Schwind Julia , Spoormaker Victor
Published: January 2025

Objective

Depression remains one of the most critical healthcare concerns worldwide. While increasing patient numbers inevitably lead to a greater need for treatment, resources to adequately match this demand are limited. Digital technologies hold promises to complement standard therapeutic approaches such as psychotherapy, thereby alleviating the strain on an increasingly burdened healthcare system. This study aimed at testing a new comprehensive smartwatch-based digital intervention program administered for 12 weeks in depressed patients to aid therapeutic progression and symptom relief.

Methods

Seventeen mildly to moderately depressed patients receiving the smartwatch-based intervention were compared to an existing, retrospective control group (35 patients). The intervention program comprised behavioral activation, cognitive-behavioral intervention for insomnia and physical activity interventions. Intervention effects on the reduction of depression severity, measured by the PHQ-9, were investigated using a repeated measure analysis of variance (rmANOVA).

Results

The rmANOVA showed a significant group x time interaction for the PHQ-9 scores,F(1, 50) = 7.21,p= 0.010, with post-hoc t-tests revealing group differences after but not before the intervention.

Conclusion

This study suggests that smartwatch-based interventions are feasible and effective in reducing mild to moderate depressive symptoms and could therefore be a promising stand-alone or complementary intervention to psychotherapy. Further research with a randomized controlled trial is required to validate these results.
High-resolution computational modeling of Transcranial Photobiomodulation: Light propagation and thermal effects
Authors: Guillen Alexander R , Truong Dennis Q , Faria Paula Cristina , Pryor Brian , de Taboada Luis , Datta Abhishek
Published: January 2025

Background

Transcranial Photobiomodulation (tPBM) is the non-invasive application of light to modulate underlying brain activity. There is increasing interest in evaluating tPBM as a therapeutic option. The typical technological questions are extent of light penetration and associated tissue temperature increases. Limited computational efforts to quantify these aspects are restricted to simplified models.

Methods

We consider a 3D high-resolution (1 mm) anatomically realistic head model to simulate tPBM at 800 nm wavelength and using power densities spanning three decades (10, 100, and 1,000) mW/cm2. The intended target was the F3 region. We also tested time-variant application at 100 mW/cm2for up to 20 minutes. Finally, tissue temperature rises for the American National Standards Institute (ANSI) safety limit of 330 mW/cm2was also investigated at a test case.

Results

Our predictions reveal that the induced cortical irradiance is largely focal demarcated by the shape and extent of the source. Around 1% of the injected irradiance reaches the gray matter. Aligned with previous efforts, the scalp accounts for the greatest loss (∼65%). The irradiance reduces to a hundredth of the value from gray matter at ∼113 mm perpendicular distance from its surface. There is a growing halo-like effect at the level of CSF which is extended down to the underlying cortex. The CSF was found to be mainly responsible for this effect. We observe scalp temperature increases of 0.38°C and 3.76°C for 100 and 1,000 mW/cm2power density, respectively. The corresponding brain temperature increases are predicted to be 0.06°C and 0.57°C. As expected, irradiance absorption is linear with applied power density. While maximum induced scalp temperature increases linearly with power density, maximum brain temperature increases less slowly with power density. Transient analysis at 100 mW/cm2power density demonstrates expected scalp temperature rise with increasing stimulation duration. Temperature rises asymptote in ∼ 10 minutes.

Conclusions

tPBM presents unique potential to directly impose desired spatial profile using simple alteration of shape and size of the source. Usage of power density of 1,000 mW/cm2exceeds scalp and brain temperature safety limits. Contrary to prior reports, light penetration can exceed >10 cm from gray matter surface.
Actomyosin and the Arp2/3 Complex Are Involved in the Internalization of Cellulose Synthase Complexes
Authors: Xu Liyuan , Zhang Weiwei , Huang Lei , Zhang Chunhua , Staiger Christopher J.
Published: January 2025

The coupling of exo- and endocytic trafficking of Cellulose Synthase Complexes (CSCs) has been proposed to be important for maintaining the population of active CSCs at the plasma membrane (PM) and thus appropriate levels of cell wall assembly. Although actin and myosin are known to participate in the late stages of exocytosis of CSCs, their exact role during CSC internalization events remains controversial. We constructed a functional, photoconvertible fluorescent mEOS2-CESA6 reporter and developed single-particle live-cell imaging approaches to visualize and quantify the dynamic behavior of CSCs at the PM during internalization. Using the small molecule inhibitor of clathrin, Endosidin 9-17 or ES9-17, we confirmed that clathrin-mediated endocytosis is a major pathway for CSC internalization. We also found that the actin cytoskeleton is involved in CSC internalization. Genetic or chemical inhibition of actin, myosin, or the Arp2/3 complex significantly reduced the frequency of CSC internalization events and prolonged the CSC pause time prior to internalization. Additionally, we found that the Arp2/3 complex contributes to the late stage of exocytosis of CSCs into the PM. These results reveal a role for actomyosin and the Arp2/3 complex in both CSC secretion as well as internalization that was previously undescribed in plant cells.

One sentence summary

Direct visualization of individual CSC internalization events reveals that actomyosin participates in CSC internalization and the Arp2/3 complex contributes to both exocytosis and internalization of CSCs through regulating the dynamic homeostasis of the cortical actin cytoskeleton.
Biocircuitry linked to exercise adaptations: impact of dose and inter-individual response heterogeneity
Authors: McAdam Jeremy S. , Craig Michael P. , Graham Zachary A. , Peoples Brandon , Tuggle S. Craig , Seay Regina S. , Lavin Kaleen M. , Sullivan Amber B. , O’Bryan Samia M. , Yang Sufen , Drummer Devin J. , Kelley Christian J. , Peri Kalyani , Bell Margaret B. , Aban Inmaculada , Cutter Gary R. , Mahyari Arash , Wen Yuan , Zhang Jin , Hira Akshay , Broderick Timothy J. , Kadakia Madhavi , Bamman Marcas M.
Published: January 2025

In a randomized, dose-response trial, we used molecular and phenomic profiling to compare responses to traditional (TRAD) endurance plus resistance training and high-intensity tactical training (HITT). Ninety-four participants (18-27 years) completed 12 weeks of TRAD or HITT followed by 4 weeks of detraining. Whilein vivophenotype improvements were not dose-dependent, a few dose-dependentex vivomuscle adaptations were overshadowed by wide-ranging inter-individual response heterogeneity (IRH). To address this, we established minimum clinically important difference (MCID) scores to classify participants by their attainment of MCIDs for functional muscle quality (fMQ) and cardiorespiratory fitness (CRF). Using differential gene expression (DGE) of muscle and exosomal microRNAs (miRs) and higher-order singular value decomposition (HOSVD), we mapped the molecular and phenomic biocircuitry of IRH. Nine miRs emerged as robust features of training adaptability, providing new insights into the integrated biocircuitry driving exercise adaptations and response heterogeneity.

In brief

We examinedin vivoandex vivoadaptations to two randomized exercise prescriptions. Individual response variability overshadowed dose dependent effects. Deep phenotyping and miR transcriptomics of serum exosomes and skeletal muscle enabled multidimensional modeling of integrated biocircuits linked to attaining clinically significant outcomes.
Combinations comprising dual β-lactams and a β-lactamase inhibitor achieve optimal synergistic inhibition ofMycobacterium abscessusgrowth
Authors: Rimal Binayak , Xie Yi , Panthi Chandra M. , Devlin Kaylyn L. , Beatty Kimberly E. , Lamichhane Gyanu
Published: January 2025

The historical model, which posits that β-lactams inhibit bacterial growth while β-lactamase inhibitors (BLIs) merely protect β-lactams from enzymatic degradation, fails to fully explain their activity againstMycobacterium abscessus(Mab). This study demonstrates that synergistic effects extend beyond the traditional one β-lactam+one BLI paradigm, refuting the oversimplified mechanistic framework. First, β-lactam-based BLIs such as clavulanic acid, sulbactam, and tazobactam exhibit intrinsic antibacterial activity againstMab. These agents synergized not only with β-lactams but also with one another, undermining their historical classification as mere β-lactamase inhibitors. The data indicate that their activity is not limited to inhibiting β-lactamases but extends to directly targeting critical bacterial processes. Second, dual β-lactam combinations exhibit synergism againstMabeven in the absence of BLIs. For example, despite being rapidly hydrolyzed by the native β-lactamase BlaMab, amoxicillin demonstrates strong synergism with β-lactams such as imipenem or ceftaroline. This suggests that the second β-lactam either acts as a functional BLI surrogate or targets complementary pathways. Supporting this, experiments using penicillin- and carbapenem-based probes revealed that β-lactams bind to multipleMabproteins simultaneously, reinforcing the idea that their synergy arises from targeting complementary essential proteins. Finally, triple combinations comprising dual β-lactam and one BLI, such as amoxicillin + ceftaroline + avibactam, achieved very high synergy, underscoring the complementary roles of dual β-lactams and BLIs. The evidence in this study necessitates a revised model that can more accurately explain the activities of β-lactams and BLIs and underscores the potential for optimizing β-lactam/BLI regimens againstMab.

IMPORTANCE

This research challenges old assumptions about how antibiotics fight bacteria, particularlyMycobacterium abscessus(Mab), a tough-to-treat infection. Traditionally, β-lactam antibiotics were thought to stop bacterial growth, while β-lactamase inhibitors (BLIs) just protected them from breakdown. However, this study reveals that BLIs like clavulanic acid can work together with another BLI or β-lactam antibiotics for stronger effects. Surprisingly, even combinations comprising two BLIs can be highly effective, showing they target multiple critical bacterial processes simultaneously. Triple combinations—two β-lactams and one BLI—proved especially powerful. These findings overturn outdated ideas, offering a smarter way to use these drugs to combat difficult infections and save lives.
A linked Genomics Sequencing and Mass Spectrometry multi-modal dataset and models for Streamlined Natural Products Discovery in Microbial Strain Libraries
Authors: Tay Dillon W. P. , Koh Winston , Ang Shi Jun , Wong Zicong Marvin , Lim Yi Wee , Heng Elena , Yeo Naythan Z. X. , Adaikkappan Krishnan , Wong Fong Tian , Lim Yee Hwee
Published: January 2025

Natural products (NP) are instrumental in drug development, but their discovery and validation remain challenging and laborious despite advances in both genomic and analytical technologies. In this study, we demonstrate the use of an integrated multi-modal characterization of a microbial strain library for enhanced natural product discovery. This characterization utilizes language- and transformer-based models, integrated through a cross-validate and rank approach to search a mass spectrometry (MS)-genome multi-modal dataset with high confidence. MS data are analysed using an in-house developed tandem mass spectral MS/MS to structural elucidation workflow (WISE) that features a combination of molecular language and transformer-based models to predict corresponding molecular structures. Simultaneously, the related genomic data is pre-processed using the protein language model (ESM2) to extract meaningful embeddings. As a proof of concept, these models and pre-processed linked MS-genome datasets were applied and validated for the rapid identification of microbial strains capable of producing three diverse natural product compounds with precision ranging from 75-100%. Our findings demonstrate the transformative potential of linked MS-genome datasets at the strain-level to accelerate natural product discovery. This approach can expand the range of biotechnological innovations beyond what is currently known and curated, while also greatly reduce the resources and effort needed for discovery.
Social License Pressure and Public Support for the Lethal Control of Dingoes in Australia
Authors: Pearson A I , Cobb M L
Published: January 2025

The lethal control of dingoes to protect livestock has been publicly funded since Australia was colonised. Although lethal dingo control had social license to operate (i.e., public support) from colonial settlers, there have been limited examinations into contemporary Australian opinions. This study explored predictive factors for Australian public support for lethal dingo control. It was hypothesised that higher social license pressure (perceptions of low procedural fairness, trust, and confidence in the government’s dingo management policies), positive attitudes toward Australian wildlife, and dog ownership would predict less support for lethal dingo control. Additionally, attitude towards Australian wildlife was predicted to mediate the relationship between social license pressure and support for lethal dingo control. Australian adults (N= 990, aged 18 – 83, 52% women) voluntarily completed an online survey, which included the Attitudes to Australian Wildlife scale and novel items. Results supported all hypotheses (p< .001). More Australians opposed lethal dingo control than supported it. Social license pressure, attitude towards Australian wildlife, and dog ownership significantly predicted support for lethal dingo control as hypothesised. Attitude towards Australian wildlife mediated the relationship between social license pressure and support for lethal dingo control with a large effect size (f2= 1.73). This study provides evidence of tenuous community support for the lethal control of dingoes. Given that a loss of social license would challenge Australia’s longstanding livestock practices, our findings are particularly useful for the proactive development of dingo management policies that the Australian public will support.

Highlights

Support for lethal dingo control was polarised, but more Australians were opposed

Unfavourable public perception of dingo policies; increasing social license pressure

Dog owners demonstrated less support for lethal dingo control than non-dog owners

Wildlife attitudes mediated social license and support for dingo control relationship

Social license to operate for lethal dingo control is tenuous in Australia
Dissipation-induced quantum homogenization for temporal information processing
Authors: Yosifov Alexander , Iyer Aditya , Vedral Vlatko
Published: January 2025

Quantum reservoirs have great potential as they utilize the complex real-time dissipative dynamics of quantum systems for information processing and target time-series generation without precise control or fine-tuning of the Hamiltonian parameters. Nonetheless, their realization is challenging as quantum hardware with appropriate dynamics, robustness to noise, and ability to produce target steady states is required. To that end, we propose the disordered quantum homogenizer as an alternative interaction model, and prove it satisfies the necessary and sufficient conditions ( and ) of the reservoir dynamics, necessary for solving machine learning tasks with time-series input data streams. The results indicate that the quantum homogenization protocol, physically implementable as either nuclear magnetic resonance ensemble or a photonic system, can potentially function as a reservoir computer.

Published by the American Physical Society
2025
Hydrogen and deuterium tunneling in niobium
Authors: Abogoda Abdulaziz , Shelton W. A. , Vekhter I. , Sauls J. A.
Published: January 2025

We use density functional methods to identify the atomic configurations of H and D atoms trapped by O impurities embedded in bulk Nb. The O atoms are located at the octahedral position in the Nb body-centered cubic (BCC) lattice, and H (D) atoms tunnel between two degenerate tetrahedral sites separated by a mirror plane. Using nudged elastic band (NEB) methods, we calculate the double-well potential for O-H and O-D impurities and the wave functions and tunnel splittings for H and D atoms. Our results agree with those obtained from analysis of heat capacity and neutron scattering measurements on Nb with low concentrations of O-H and O-D.

Published by the American Physical Society
2025
Chiral versus deconfinement properties of the QCD crossover: Differences in the volume and chemical potential dependence from the lattice
Authors: Borsányi Szabolcs , Fodor Zoltán , Guenther Jana N. , Kara Ruben , Parotto Paolo , Pásztor Attila , Pirelli Ludovica , Wong Chik Him
Published: January 2025

The crossover from hadronic to quark matter is understood to be both a deconfinement as well as a chiral symmetry–restoring transition. The precise definition of these aspects may be ambiguous. Here we use the static quark free energy and its temperature derivative as proxies for deconfinement and the chiral condensate and its mass derivatives for the chiral transition. At zero baryochemical potential, and infinite volume, the chiral and deconfinement crossover temperatures almost agree. However, as we vary the spatial volume of the simulation, we observe that chiral and deconfinement-related observables have a qualitatively different chemical potential and volume dependence. In general, deconfinement-related observables have a milder volume dependence. Furthermore, while the deconfinement transition appears to get broader with increasing μB, the width as well as the strength of the chiral transition is approximately constant. Our results are based on simulations at zero and imaginary chemical potentials using 4-stout-improved staggered fermions with Nτ=12 time slices and physical quark masses.

Published by the American Physical Society
2025
Dynamics of microscale and nanoscale systems in the weak-memory regime: A mathematical framework beyond the Markov approximation
Authors: Brandner Kay
Published: January 2025

The visible dynamics of small-scale systems are strongly affected by unobservable degrees of freedom, which can belong to either external environments or internal subsystems and almost inevitably induce memory effects. Formally, such inaccessible degrees of freedom can be systematically eliminated from essentially any microscopic model through projection operator techniques, which result in nonlocal time evolution equations. This article investigates how and under what conditions locality in time can be rigorously restored beyond the standard Markov approximation, which generally requires the characteristic timescales of accessible and inaccessible degrees of freedom to be sharply separated. Specifically, we consider nonlocal time evolution equations that are autonomous and linear in the variables of interest. For this class of models, we prove a mathematical theorem that establishes a well-defined weak-memory regime, where faithful local approximations exist, even if the relevant timescales are of comparable order of magnitude. The generators of these local approximations, which become exact in the long-time limit, are time independent and can be determined to arbitrary accuracy through a convergent perturbation theory in the memory strength, where the Markov generator is recovered in first order. For illustration, we work out three simple, yet instructive, examples covering coarse-grained Markov jump networks, semi-Markov jump processes, and generalized Langevin equations.

Published by the American Physical Society
2025
Cut it out: Out-of-plane stresses in cell sheet folding of
Volvox
embryos
Authors: Haas Pierre A. , Höhn Steph S. M. H.
Published: January 2025

The folding of cellular monolayers pervades embryonic development and disease, and is often caused by cell shape changes such as cell wedging. However, the function and mechanical role of different active cellular changes in different regions of folding tissues remain unclear in many cases, at least partially because the quantification of out-of-plane mechanical stresses in complex three-dimensional tissues has proved challenging. The gastrulationlike inversion process of the green alga provides a unique opportunity to overcome this difficulty: Combining laser ablation experiments and a mechanical model, we infer the mechanical properties of the curved tissue from its unfurling on ablation. We go on to reproduce the tissue shapes at different developmental timepoints quantitatively using our mechanical model. Strikingly, this reveals out-of-plane stresses associated with additional cell shape changes away from those regions where cell wedging bends the tissue. Moreover, the fits indicate an adaptive response of the tissue to these stresses. In this way, our paper provides not only the experimental and theoretical framework to quantify out-of-plane stresses in tissue folding, but it also shows how additional cell shape changes can provide another source of out-of-plane stresses in development complementing cell wedging.

Published by the American Physical Society
2025
Study of the atmospheric neutron radiation effects using compact laser-driven spallation neutron source
Authors: Wu Z. B. , Yao Y. L. , Shen X. F. , Li K. , Liu A. D. , He X. T. , Qiao B.
Published: January 2025

We propose a laboratory accelerated test method for study of the atmospheric neutron radiation effects by using a compact laser-driven spallation neutron source (LDSNS). The LDSNS is obtained by injecting a GeV quasimonoenergetic proton beam accelerated by light-sail (LS) radiation pressure of intense lasers into a lead target. According to the LS scaling law, proton energy spectra can be regulated by adjusting the laser and foil target parameters, so that the neutron spectra at various atmospheric altitudes are well reproduced. Integrated PIC and MC simulations have verified the scheme (for that at altitude 12 km, laser intensity of 1022W/cm2 is required) and shown that the neutron fluence per laser shot is as high as 1.73×108n/cm2, equivalent to 3.7 year flux accumulation in atmosphere. Using the G4SEE toolkit, we estimate that the HM628128 SRAM may undergo an average of ten single event upsets per shot for the proposed laboratory test.

Published by the American Physical Society
2025
Neural quantum propagators for driven-dissipative quantum dynamics
Authors: Zhang Jiaji , Benavides-Riveros Carlos L. , Chen Lipeng
Published: January 2025

Describing the dynamics of strong-laser driven open quantum systems is a very challenging task that requires the solution of highly involved equations of motion. While machine learning techniques are being applied with some success to simulate the time evolution of individual quantum states, their use to approximate time-dependent operators (that can evolve various states) remains largely unexplored. In this work, we develop driven (NQP), a universal neural network framework that solves driven-dissipative quantum dynamics by approximating propagators rather than wave functions or density matrices. NQP can handle arbitrary initial quantum states, adapt to various external fields, and simulate long-time dynamics, even when trained on far shorter time windows. Furthermore, by appropriately configuring the external fields, our trained NQP can be transferred to systems governed by different Hamiltonians. We demonstrate the effectiveness of our approach by studying the spin-boson and the three-state transition Gamma models.

Published by the American Physical Society
2025
Extreme weather events and economic growth: empirical evidence from Africa
Authors: Insaidoo Michael , Kunawotor Mark Edem , Ahiabor Godson
Published: January 2025

Purpose

The persistent occurrence of extreme weather events redirects both public and private resources, constrains economic expansion, employment opportunities and threatens the well-being of Africans. To provide an empirical econometric update, this study examines the unconditional effects of extreme weather events on economic growth. Also, it disaggregates weather events into floods and droughts to determine which is more consequential to economic growth. The paper further examines the distribution of economic growth at which extreme weather events may be more consequential.

Design/methodology/approach

The study deploys the system generalized method of moments estimation strategy, in addition to the method of moment quantile regression.

Findings

The results show that extreme weather event is detrimental to economic growth. Among the types of weather events, the incidence of drought has a consequential impact on economic growth while floods do not.

Practical implications

The gross implication of these findings is that policy makers and governments in Africa need to be proactive at least in devising robust adaptive capacities to combat extreme weather events. Also, more efforts need to be invested in understanding the adverse effects of extreme weather events on economic growth.

Originality/value

This study provides novel econometric evidence on the effects of extreme weather events on economic growth and disaggregates weather events into floods and droughts. In addition, the study examines the distributions of economic growth at which extreme weather events may be more consequential.
Interactive or not? Enhancing the interactive effectiveness of virtual brand ambassadors on consumer behavior
Authors: Shen Zheng
Published: January 2025

Purpose

Nowadays, more and more brands are developing their own virtual ambassadors for interactive communication and marketing with consumers. Exploring the interactive effectiveness of virtual brand ambassadors on consumer behavior is crucial to understanding the interactions between brands, virtual ambassadors and consumers as well as further increasing consumer engagement in AI-mediated interactive marketing.

Design/methodology/approach

This study investigated different interactive effects of virtual ambassadors on consumer behavior in terms of virtual ambassadors’ anthropomorphism, virtual experience and consumer behavior through a mixed method of questionnaires and semi-structured interviews.

Findings

The results indicate that consumers’ sharing, reviewing and purchasing behavior is significantly and positively influenced by virtual ambassadors’ anthropomorphism and virtual experience. In addition, specific anthropomorphic features and virtual experiences were discussed in detail.

Originality/value

This study helps brands develop and manage their virtual ambassadors and consumers in AI-mediated interactive marketing and communication.