bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial performance improvement after iron replacement in heart failure patients: The IRON-PATH II echo-substudy
Authors: Ramos-Polo Raúl , Ras-Jiménez Maria del Mar , Carbajales María del Carmen Basalo , Jovells-Vaqué Sílvia , Garcia-Pinilla José Manuel , Cobo-Marcos Marta , de Juan-Bagudá Javier , Fonseca Cândida , Manzano Josep Francesch , Cosa Andreea Eunice , Yun-Viladomat Sergi , Enjuanes Cristina , Orduña Marta Tajes , Comin-Colet Josep
Published: February 2025

Iron deficiency (ID) is a prevalent comorbidity in heart failure (HF) patients associated with poor prognosis and impaired physical capacity. Functional limitations linked to ID may be related to cardiac function abnormalities, which could be reversible with iron repletion. Some echocardiographic parameters, such as global longitudinal strain (GLS), myocardial work (MW), and its derivatives constructive work (CW), wasted work (WW), and work efficiency (WE), may provide additive value in advanced cardiac performance assessment. The IRON-PATH II was a multicenter, prospective and observational study designed to describe pathophysiological pathways associated to ID. The echo-substudy included 100 HF patients undergoing a specific pilot echocardiographic evaluation. Patients had left ventricular ejection fraction (LVEF) ≤50%, were in stable clinical condition, on standard HF medication, and with hemoglobin ≥11 g/dL. The final cohort included 98 patients. The ID group showed worse cardiac function, with lower GLS (–8.5±9% vs –10±10%), WE (74±10% vs 80±10%), and MW (665[453-1013] vs 947[542-1199] mmHg%), as well as higher WW (290[228-384] vs 212[138-305] mmHg%) and lower RV free wall strain (–13[-20-(–11)] % vs –17[-23-(–14)] %). Following iron repletion, ID patients demonstrated improved LV (GLS, MW, WE, and WW) and RV performance (RV free wall strain), aligning with non-ID patients (all p-values >0.05 compared to the non-ID group). In conclusion, among HF patients with reduced LVEF, ID was associated with worse myocardial performance in both the LV and RV, with these alterations being reversible after intravenous iron repletion.

Abstract Figure

Graphical Abstract
Detecting Primary Progressive Aphasia (PPA) from Text: A Benchmarking Study
Authors: Merhbene Ghofrane , Lecron Fabian , Fortemps Philippe , Dickerson Bradford C , Kurpicz-Briki Mascha , Rezaii Neguine
Published: February 2025

Classifying subtypes of primary progressive aphasia (PPA) from connected speech presents significant diagnostic challenges due to overlapping linguistic markers. This study benchmarks the performance of traditional machine learning models with various feature extraction techniques, transformer-based models, and large language models (LLMs) for PPA classification. Our results indicate that while transformer-based models and LLMs exceed chance-level performance in terms of balanced accuracy, traditional classifiers combined with contextual embeddings remain highly competitive. Notably, SVM using RoBERTa's embeddings achieves the highest classification accuracy. These findings underscore the potential of machine learning in enhancing the automatic classification of PPA subtypes.
Sex differences distinguish performance in four object recognition-based memory tasks in the Pink1-/- rat model of Parkinson’s disease
Authors: Desai Aveena M. , Aje Oluwagbohunmi A. , Kritzer Mary F.
Published: February 2025

Many patients with Parkinson’s disease (PD) experience early, sometimes prodromal non-motor deficits involving cognition and memory. These so-called mild cognitive impairments hold dire predictions for future risk of freezing, falls and developing PD-related dementia. Moreover, due to a dearth of effective treatments, these symptoms persist and progressively worsen. Thus, there is an urgent need to better understand and better treat these debilitating signs. Sex differences in incidence, severity and treatment sensitivities predict that the answers to these questions are sex-specific. The work presented here highlights new ways in which rats with knockout of PTEN-induced putative kinase 1 gene (Pink1-/-) emulate PD’s mild cognitive deficits and their clinical sex differences. Specifically, longitudinal behavioral testing confirmed that male Pink1-/- rats developed significant deficits in Novel Object Recognition and Novel Object Location tasks by 5 months old but that female Pink1-/- were unimpaired in these and the Object-in-Place task through 12 months of age. Further, What, Where, When Episodic-like Memory testing identified enduring deficits in all three memory domains in Pink1-/- males by 3 months of age whereas in Pink1-/- females, non-significant impairments emerged at 7 months of age and progressed to significant memory deficits by 12 months of age. Together, these data show that Pink1-/- rats model the generally greater vulnerability of male PD patients to cognitive and memory deficits in PD, the growing risk for higher order deficits in female patients as they age, and features including early onset that distinguish episodic memory impairments from other at-risk processes in this disorder.
The experience and perception of first language usage in healthcare: the Welsh perspective
Authors: Edwards Maisie E , Bodger Owen , Brown Menna , Roberts Llinos , Roberts Luke D , Davies Jeffrey S , Morgan Alwena H
Published: February 2025

Several studies have shown that using language that is most suitable for the patient is essential for effective communication in healthcare. Using a patients second language during health consultations can negatively impact a patient, causing delays in treatment and misdiagnosis. In Wales both Welsh and English have equal status in public sector organisations, however, independent primary care providers such as General Practices (GPs), do not need to comply with all the Welsh Language Standards. Thus, there is inconsistency in the availability of bilingual healthcare provision. This mixed methods study used a focus group and a survey of the Welsh speaking general population (361 participants) to gauge awareness of the Welsh Language Standards and collect experiences of bilingual healthcare, concentrating on GPs. The data underwent both qualitative thematic and quantitative analysis and revealed low awareness of the Welsh Language Standards (27%). Overall, respondents felt that their need to use Welsh is not taken seriously, with 71% having never been offered a Welsh consultation. 57% that have an English medium doctor reported that they would feel more comfortable having their consultations in Welsh. 32% of respondents from higher percentage Welsh speaking areas have felt restricted by their inability to communicate in their first language during GP appointments. There was overwhelming support for recording a patient’s preferred language on health records. The results suggest that the Welsh speaking public both want and need Welsh provision in primary care. However, there is a need to review primary care policies to facilitate a more effective roll out of an ‘active offer’ of first language healthcare in Wales.
β-Amyloid Induces Microglial Expression of GPC4 and APOE Leading to Increased Neuronal Tau Pathology and Toxicity
Authors: Holmes Brandon B. , Weigel Thaddeus K. , Chung Jesseca M. , Kaufman Sarah K. , Apresa Brandon I. , Byrnes James R. , Kumru Kaan S. , Vaquer-Alicea Jaime , Gupta Ankit , Rose Indigo V. L. , Zhang Yun , Nana Alissa L. , Alter Dina , Grinberg Lea T. , Spina Salvatore , Leung Kevin K. , Condello Carlo , Kampmann Martin , Seeley William W. , Coutinho-Budd Jaeda C. , Wells James A.
Published: February 2025

To elucidate the impact of Aβ pathology on microglia in Alzheimer’s disease pathogenesis, we profiled the microglia surfaceome following treatment with Aβ fibrils. Our findings reveal that Aβ-associated human microglia upregulate Glypican 4 (GPC4), a GPI-anchored heparan sulfate proteoglycan (HSPG). In aDrosophilaamyloidosis model, glial GPC4 expression exacerbates motor deficits and reduces lifespan, indicating that glial GPC4 contributes to a toxic cellular program during neurodegeneration. In cell culture, GPC4 enhances microglia phagocytosis of tau aggregates, and shed GPC4 can actin transto facilitate tau aggregate uptake and seeding in neurons. Additionally, our data demonstrate that GPC4-mediated effects are amplified in the presence of APOE. These studies offer a mechanistic framework linking Aβ and tau pathology through microglial HSPGs and APOE.
Dynamic fingerprinting of the human functional connectome
Authors: Ghaffari Amin , Zhao Yufei , Chen Xu , Langley Jason , Hu Xiaoping
Published: February 2025

Resting-state functional connectivity (FC) have distinct, personalized patterns that could serve as a unique fingerprint of each individual’s brain. While previous brain fingerprinting methods have used functional connectivity maps over a scanning session (static method), it has been shown that the brain is a dynamic system that switches between several metastable states, each of which having a different FC map. Taking the dynamic nature of brain connectivity into account will likely lead to more subject-specific information and better individual identification. In this paper, we derived the state-specific FCs using sliding window correlation and clustering and evaluated their performance in individual identification and cognitive score prediction. The resultant dynamic fingerprints outperformed the static fingerprints in identification accuracy. Furthermore, some of the brain states were more accurate in predicting cognitive scores, indicating that connectivity in some brain states is informative of cognition abilities, possibly useful as biomarkers for brain disorders.

Impact Statement

Our findings suggest that state-specific functional connectivity patterns of the brain are unique for each individual. These brain states predicted participants’ cognitive performance, suggesting that they have the potential to be used as biomarkers for cognitive function or neurological disorders. Integrating state-based functional connectivity into clinical frameworks could potentially enhance early diagnosis and patient stratification, and lead to targeted interventions for neuropsychiatric and neurodegenerative conditions.
Triphenylphosphonium is an effective targeting moiety for plants mitochondria
Authors: Lazary Shani , Maman Gal , Binenbaum Jenia , Ronen Mordechai , Tal Iris , Yariv Elon , Shani Eilon , Weinstain Roy
Published: February 2025

Small signaling molecule regulates key physiological processes in plants, often in a spatially distinct manner. However, current methods for applying small-molecules, endogenous or synthetic, in plants research lack spatial precision, limiting the ability to study and utilize their localized effects. Here, we validate triphenylphosphonium (TPP) as a mitochondrial targeting motif in plants. Using fluorescently labeled TPP conjugates in Arabidopsis thaliana, we demonstrate mitochondria-specific accumulation, even in the presence of plastids. This precise localization enables detailed imaging of mitochondria and mitochondrial DNA in living plants. We further exploit this targeting ability by developing a TPP-ciprofloxacin conjugate to selectively inhibit mitochondrial DNA gyrase, an enzyme involved in organellar DNA replication. Unlike free ciprofloxacin, which disrupts both mitochondrial and chloroplast DNA gyrase activity, the TPP-conjugate specifically targets mitochondrial gyrase, leading to slower plant growth without affecting chloroplast function. This targeted inhibition triggers a mitochondrial retrograde response, characterized by increased reactive oxygen species levels and the upregulation of stress-response genes in the nucleus. Our findings establish TPP as a reliable tool for mitochondrial targeting in plants and open avenues for both fundamental research and agricultural applications. By enabling organelle-specific manipulation in species not amenable to genetic engineering, TPP-based strategies have potential for advancing plant biology and precision agriculture.
An integrated system for comprehensive mouse peripheral vestibular function evaluation based on Vestibulo-ocular Reflex
Authors: Zhao Tong , Xiao Shijie , Liu Wenda , Zhong Jinhao , Sun BinXian , Chen Fangyi
Published: February 2025

In the realms of both vestibular and auditory research, conducting vestibular function tests is essential. However, unlike the auditory function tests which utilize standard equipment such as the Auditory Brainstem Response (ABR) device, there is no equivalent widely adopted apparatus for vestibular tests. This is largely due to the intricate nature of the vestibular system and the challenges associated with assessing its functions. Vestibulo-ocular reflexes (VORs) are the compensatory ocular reflexes that ensure stable vision during head motion. VORs are widely used in clinics for diagnosing the vestibular deficit. In the research field, VORs, including angular VOR (aVOR) or off-vertical axis rotation (OVAR) tests, have been used by various groups to evaluate the mouse vestibular function. However, the effectiveness of VOR tests has not been systematically evaluated with proper animal models, and the lack of commercial equipment hampers its accessibility, confining vestibular testing to a select few labs. In this study, we developed an integrated instrument system with both aVOR and OVAR modes for evaluating mouse vestibular function. To demonstrate its efficacy, peripheral vestibular animal models, 1) Vestibulotoxicity drugs 3,3’-iminodiproprionitrile (IDPN, 2 mg/g and 4 mg/g) induced; 2) Critical MET-related mutant (Cdh23v2J/v2JandTMC1-/-); 3) Vestibulo-specific mutant (Zpld1-/-for semicircular canal dysfunction andOtop1tlt/tltfor otoconia deficient; 4) Unilateral vestibular lesion (UVL) model by injecting gentamicin into horizontal semicircular canal, were constructed and evaluated with the system. The results showed 1) Quantification of the vestibular deficit is achieved in a daily manner; 2) Both the otolith organ and semicircular canals can be assessed respectively; and 3) The lesion side of UVL can be identified. During an 8-week study of IDPN vestibulotoxicity, the vestibular function of 3 groups of 20 animals was evaluated at 15 test days. These test results reveal the potential of our system as a standard system for evaluating common vestibular deficits in mice.
Interdigitating Modules for Visual Processing During Locomotion and Rest in Mouse V1
Authors: Meier Andrew M , D'Souza Rinaldo David , JI Weiqing , Han Edward B , Burkhalter Andreas
Published: February 2025

Layer 1 of V1 has been shown to receive locomotion-related signals from the dorsal lateral geniculate (dLGN) and lateral posterior (LP) thalamic nuclei (Roth et al., 2016). Inputs from the dLGN terminate in M2+ patches while inputs from LP target M2- interpatches (D’Souza et al., 2019) suggesting that motion related signals are processed in distinct networks. Here, we investigated by calcium imaging in head-fixed awake mice whether L2/3 neurons underneath L1 M2+ and M2- modules are differentially activated by locomotion, and whether distinct networks of feedback connections from higher cortical areas to L1 may contribute to these differences. We found that strongly locomotion-modulated cell clusters during visual stimulation were aligned with M2- interpatches, while weakly modulated cells clustered under M2+ patches. Unlike M2+ patch cells, pairs of M2- interpatch cells showed increased correlated variability of calcium transients when the sites in the visuotopic map were far apart, suggesting that activity is integrated across large parts of the visual field. Pathway tracing further suggests that strong locomotion modulation in L2/3 M2- interpatch cells of V1 relies on looped, like-to-like networks between apical dendrites of MOs-, PM- and RSP-projecting neurons and feedback input from these areas to L1. M2- interpatches receive strong inputs from SST neurons, suggesting that during locomotion these interneurons influence the firing of specific subnetworks by controlling the excitability of apical dendrites in M2- interpatches.
Sleep Resolves Competition Between Explicit and Implicit Memory Systems
Authors: Kleespies Katja , Paulus Philipp C. , Zhu Hao , Pargent Florian , Jakob Marie , Werle Jana , Czisch Michael , Boedecker Joschka , Gais Steffen , Schönauer Monika
Published: February 2025

Sleep supports stabilization of explicit, declarative memory and benefits implicit, procedural memory. In addition, sleep may change the quality of memory representations. Explicit and implicit learning systems, usually linked to the hippocampus and striatum, can compete during learning, but whether they continue to interact during offline periods remains unclear. Here, we investigate for feedback-driven classification learning, whether sleep integrates explicit and implicit aspects of memory. The negative relationship between implicit and explicit memory components was resolved over sleep, but not wakefulness. Additionally, sleep benefitted performance on a task that allows the cooperative use of explicit and implicit memory, and participants who slept showed superior performance in generalizing their knowledge to unseen exemplars. A reinforcement learning model relates this to better transfer of the learned exemplar value representation after sleep. This suggests that sleep integrates information learned by different routes and helps us respond optimally to everyday life contingencies.
The implementation of KPI (key performance indicators) to manage the Pharmacovigilance System of a public vaccine producer in Brazil
Authors: Oliveira Mayra M. M. , Oliveira Fernanda L. C. , Gattás Vera L. , Santos Clarissa L. , Wagner Gabriela A. , Taminato Monica
Published: February 2025

Background

Pharmacovigilance (PV) is a critical science aimed at enhancing patient safety. For a pharmacovigilance system (PVS) to be effective, it must be robust, efficient, and regularly evaluated to ensure ongoing improvement. Key Performance Indicators (KPIs) are essential quantifiable measures that evaluate the performance of companies, processes, and systems, including pharmacovigilance.

Aim

This study aimed to implement and evaluate KPIs for the PVS of a public vaccine producer in Brazil, identifying improvement areas and supporting continuous enhancement.

Methods

KPI selection for Instituto Butantan’s PVS was guided by a systematic review and benchmarking with pharmaceutical representatives, followed by validation through expert consensus. A dashboard was created for KPI implementation, with goals, measurements, and evaluation frequency detailed in the institution’s Standard Operating Procedure (SOP).

Results

The review identified one KPI for a Marketing Authorization Holder (MAH) PV process. Interviews with pharmaceutical company representatives led to 25 additional KPIs, with one overlapping. After expert review, all KPIs were approved after adjustments, and 10 were piloted, including metrics like the number of individual case safety reports (ICSR), ICSR per product, and serious adverse events (SAE) per product. A dashboard tracked these KPIs monthly in 2022 and 2023.

Conclusion

Over two years, KPI evaluations proved valuable, prompting improvements in PV processes and tools. Results indicated that expanding to the remaining KPIs would further enhance Instituto Butantan’s PVS.

Pharmacovigilance, Key Performance Indicators (KPIs), Quality Improvement
Mapping the bird reservoir potential for West Nile virus in Europe and its relationship with disease occurrence in humans
Authors: Bastard Jonathan , Métras Raphaëlle , Durand Benoit
Published: February 2025

Background

West Nile virus (WNV) is a zoonotic mosquito-borneFlavivirus, with bird populations reservoirs. Although often asymptomatic, infection in humans can cause febrile symptoms and more rarely, severe neurological symptoms that may lead to death. Mapping WNV bird reservoir is important towards understanding the distribution of WNV cases in humans.

Aim

Our objective was to generate a WNV Reservoir Index (RI), quantifying the bird reservoir potential across Europe, and validate the RI using human cases notifications.

Methods

We first used a bird traits-based model to estimate WNV seroprevalence in 150 European passerine bird species. This allowed us to build a map of the WNV bird RI across Europe. To validate this metric, we investigated its association with WNV human cases notified at the NUTS administrative region scale, using a Besag-York-Mollie spatial model in a Bayesian framework.

Results

We first identified eco-ethological characteristics associated with higher WNV seroprevalence in wild birds. Second, we mapped the RI that showed a strong spatial heterogeneity across Europe, with overall high RI values (i.e. a high reservoir potential for WNV) in Central and Eastern Europe, despite variations at small geographical scale. At the NUTS level, the RI was positively associated with the number of years with notified WNV human cases between 2016 and 2023.

Conclusions

We provide a map quantifying the suitability for WNV to circulate in the bird reservoir. This allows to target surveillance efforts in areas at risk for WNV zoonotic infections in the future.
Neurometabolic signaling and control of policy complexity
Authors: Tesmer Alexander L. , Pola Christine Dalla , Gilli Dino , Grujic Nikola , Bracey Eva F. , Patriarchi Tommaso , Peleg-Raibstein Daria , Polania Rafael , Burdakov Denis
Published: February 2025

Cognition and adaptive behavior emerge from neural information processing. This must operate within finite metabolic constraints, since neural information processing is metabolically expensive. While neural implementations of action selection and learning are well-studied, systems allocating the informational capacity required to encode complex behavioral policies remain unknown. We hypothesized that hypothalamic hypocretin/orexin neurons (HONs) are uniquely positioned to signal and control policy complexity, given that they are activated by metabolic depletion and influence decision-making systems. To explore this, we employed a set of cell/neurotransmitter-specific imaging and causal manipulations during a multi-armed bandit task where freely behaving mice learned probabilistic state-action-reward relationships (together ∼100,000 decisions from >100 mice). Miniscope recordings of HON activity revealed that pre-choice, but not post-choice activity correlates with decision policy, dissociating decisions from feedback. Furthermore, manipulating HON signals with optogenetics and pharmacology confirmed that they causally regulate the development of complex policies. Finally, neurotransmitter-specific sensors revealed that hypocretin/orexin receptors modulate decision policy-related dopamine and noradrenaline dynamics in the nucleus accumbens and medial prefrontal cortex. These findings identify HONs as subcortical regulators of policy complexity, encoding critical signals for decision-making adjustments. This opens a new window for the development of comprehensive mechanistic models of strategic learning which account for interplay between decision-making policies and metabolic/informational constraints, and may guide the development of potential treatments for disorders with policy deficits such as autism and schizophrenia.
MIG-21 is a novel regulator of Wnt and Netrin signaling in gonad migration identified from published scRNA-seq data and functionally validated inC. elegans
Authors: Li Xin , Gordon Kacy Lynn
Published: February 2025

Using a recently published scRNA-seq dataset of adultC. eleganshermaphrodites, we identified a previously unknown regulator of the germ line stem cell niche (the distal tip cell, or DTC). The genemig-21has the highest “marker score”–yet no known role–in the DTC. Using classical genetics techniques, RNAi knockdown, and live cell imaging, we discovered thatmig-21integrates information from the Wnt and Netrin pathways to guide anteroposterior and dorsoventral DTC migration. Our study demonstrates the utility of scRNA-seq datasets in revealing testable hypotheses about genetic networks that were masked by redundancy in traditional screening methods.
Agonistic behavior and fear response during consecutive encounters in female fish
Authors: Salustri Chiara , cavallino luciano , Brasca Mariano , Pozzi Andrea , Scaia Maria Florencia
Published: February 2025

While consecutive agonistic encounters modulating aggressive behavior are well studied in males, the extent to which social behavior can be altered by fear sensing during consecutive agonistic encounters remains unexplored. A well-established paradigm to assess fear sensing is the exposure to alarm substances (AS) from conspecifics in Ostariophysi fish, such as zebrafish, which causes several physiological and behavioral changes associated to distress. Considering that the exposure to AS induces changes in individual behavior associated to fear response, the aim of the present work is to examine whether repeated exposure to AS alters both agonistic behavior and fear response in female zebrafish. Moreover, since female aggression is understudied when compared to males, this study also assesses possible differences according to the reproductive stage. We performed intrasexual dyadic encounters between female zebrafish to determine if agonistic behavior is altered during two consecutive contests and by the presence of AS. When comparing agonistic behavior in different reproductive stages, results suggest there are no differences in latency and in freezing. Regarding time of aggression, while there are no differences between contests in prespawning or postspawning, significant differences are detected between postspawning dyads and mixed dyads with both females in different reproductive stages. Results suggest that exposure to AS reduces female motivation to engage in an agonistic encounter while aggressive behavior is still maintained despite sensing AS as potential threat, regardless of corresponding to the first or second contest. Finally, similar to agonistic behavior, the effect of fear sensing on individual behavioral parameters such as distance, mean velocity and freezing is also observed during a first and also a second exposure to AS. To the best of our knowledge, this is the first evidence assessing how consecutive agonistic encounters with a real opponent can be altered by repeated exposure to AS.
Intersecting impact of CAG repeat and Huntingtin knockout in stem cell-derived cortical neurons
Authors: Stocksdale Jennifer T. , Leventhal Matthew J. , Lam Stephanie , Xu Yu-Xin , Wang Yang Oliver , Wang Keona Q. , Tomas Reuben , Faghihmonzavi Zohreh , Raghav Yogi , Smith Charlene , Wu Jie , Miramontes Ricardo , Sarda Kanchan , Johnson Heather , Shin Min-Gyoung , Huang Terry , Foster Mikelle , Barch Mariya , Armani Naufa , Paiz Chris , Easter Lindsay , Duderstadt Erse , Vaibhav Vineet , Sundararaman Niveda , Felsenfeld Dan P. , Vogt Thomas F. , Van Eyk Jennifer , Finkbeiner Steve , Kaye Julia A. , Fraenkel Ernest , Thompson Leslie M.
Published: February 2025

Huntington’s Disease (HD) is caused by a CAG repeat expansion in the gene encoding Huntingtin (HTT). While normal HTT function appears impacted by the mutation, the specific pathways unique to CAG repeat expansion versus loss of normal function are unclear. To understand the impact of the CAG repeat expansion, we evaluated biological signatures of HTT knockout (HTTKO) versus those that occur from the CAG repeat expansion by applying multi-omics, live cell imaging, survival analysis and a novel feature-based pipeline to study cortical neurons (eCNs) derived from an isogenic human embryonic stem cell series (RUES2).HTTKO and the CAG repeat expansion influence developmental trajectories of eCNs, with opposing effects on the growth. Network analyses of differentially expressed genes and proteins associated with enriched epigenetic motifs identified subnetworks common to CAG repeat expansion andHTTKO that include neuronal differentiation, cell cycle regulation, and mechanisms related to transcriptional repression and may represent gain-of-function mechanisms that cannot be explained byHTTloss of function alone. A combination of dominant and loss-of-function mechanisms are likely involved in the aberrant neurodevelopmental and neurodegenerative features of HD that can help inform therapeutic strategies.
Axially decoupled photo-stimulation and two photon readout (ADePT) for mapping functional connectivity of neural circuits
Authors: Koh Matthew , Anselmi Francesca , Kaushalya Sanjeev K. , Hernandez Diego E. , Bast Walter Germán , Villar Pablo S. , Chae Honggoo , Davis Martin B. , Teja Sadhu Sai , Qu Zhe , Gradinaru Viviana , Gupta Priyanka , Banerjee Arkarup , Albeanu Dinu F.
Published: February 2025

All optical physiologyin vivoprovides a conduit for investigating the function of neural circuits in 3-D. Here, we report a new strategy for flexible, axially-decoupled photo-stimulation and two photon readout (ADePT) of neuronal activity. To achieve axially-contained widefield optogenetic patterned stimulation, we couple a digital micro-mirror device illuminated by a solid-state laser with a motorized holographic diffuser. In parallel, we use multiphoton imaging of neural activity across different z-planes. We useADePTto analyze the excitatory and inhibitory functional connectivity of the mouse early olfactory system. Specifically, we control the activity of individual input glomeruli on the olfactory bulb surface, and map the ensuing responses of output mitral and tufted cell bodies in deeper layers. This approach identifies cohorts ofsistermitral and tufted cells, whose firing is driven by the same parent glomerulus, and also reveals their differential inhibition by other glomeruli. In addition, selective optogenetic activation of glomerular GABAergic/dopaminergic (DAT+) interneurons triggers dense, but spatially heterogeneous suppression of mitral and tufted cell baseline activity and odor responses, further demonstrating specificity in the inhibitory olfactory bulb connectivity. In summary,ADePTenables high-throughput functional connectivity mapping in optically accessible brain regions.
Tryptophan metabolites as biomarkers to predict the severity and prognosis of acute ischemic stroke patients
Authors: Pan Chuzheng , Chen Feng , Yan Yan , Li Haiwen , Qiu Chengfeng
Published: February 2025

Background

A growing body of evidence indicates alterations in metabolite levels and enzyme activities associated with the conversion of tryptophan (TRP) throughout the course of cerebral ischemia. In this study we aim to explore the potential relationship between TRP metabolism and clinical prognosis in acute ischemic stroke (AIS) patients of mainland China.

Methods

Blood samples were obtained from a cohort of 304 patients diagnosed with AIS. The concentrations of ten TRP metabolites were quantified utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Stroke severity was evaluated upon admission using the National Institutes of Health Stroke Scale (NIHSS). A poor functional outcome was defined as modified Rankin scale (mRS) > 3, whereas a good functional outcome was defined by mRS ≤ 3 at 3 months post-stroke. LASSO regression and random forest algorithms were then employed to identify key TRP metabolism parameters associated with prognosis.

Results

Following the optimization of variable selection through Lasso regression, a prognostic risk model with 7-factors related to AIS was constructed, yielding an AUC of 0.917. Subsequently, a random forest analysis was conducted to establish an 11-factor prognostic risk model, which demonstrated an enhanced AUC of 1.000. Ultimately, three robust parameters related to TRP metabolism were identified. Multivariable logistic regression analysis, adjusted for covariates, revealed that TRP (odds ratio [OR] = 0.46, 95% confidence interval [CI]: 0.26 - 0.76,p= 0.004), the kynurenine (KYN)/TRP ratio (OR = 2.06, 95% CI: 1.23 - 3.60,p= 0.008), and the kynurenic acid (KYNA)/TRP ratio (OR = 2.15, 95% CI: 1.23 - 4.12,p= 0.014) were independently associated with poor functional prognosis.

Conclusions

The results of this study indicate that TRP metabolism is associated with the severity and prognosis of AIS. The TRP, KYN/TRP ratio and KYNA/TRP ratio may serve as potential biomarkers for 3-month prognostic evaluation.
Quantum information flow in impurity qubits interacting with Bose-Bose mixtures
Authors: Boudjemâa Abdelâali , Xu Lan , Tan Qing-Shou
Published: February 2025

We investigate the dynamics of quantum information flow in one and two impurity qubits trapped in a double-well potential and interacting with a one-dimensional ultracold Bose-Bose mixture reservoir. For a single qubit immersed in a binary Bose mixture, we show that the system maintains coherence over finite timescales and exhibits non-Markovian dynamics, particularly in the upper branch of the environment. We explore the transition from Markovian to non-Markovian dephasing through the Ohmicity of the spectral density functions, which are significantly influenced by interspecies interactions. In the case of two spatially separated qubits coupled to the Bose-Bose mixture reservoir, we demonstrate that collective decoherence affects the system dynamics, leading to prolonged coherence survival in both branches of the mixture. The intricate evolution of the decoherence factors is reflected in the density spectral functions and their Ohmicity characteristics. We find that the decoherence functions and spectra oscillate with increasing distance between the qubits, modifying the information flow dynamics. Additionally, we conduct a thorough investigation of the entanglement dynamics between the two qubits induced by the binary Bose mixture reservoir in both branches, underscoring the critical role of interspecies interactions.

Published by the American Physical Society
2025
Two-dimensional Planck spectroscopy for microwave photon calibration
Authors: Gandorfer S. , Renger M. , Yam W.K. , Fesquet F. , Marx A. , Gross R. , Fedorov K.G.
Published: February 2025

Quantum state tomography of weak microwave signals is an important part of many protocols in the field of quantum information processing with superconducting circuits. This step typically relies on an accurate estimation of signal losses in the experimental setup and requires a careful photon-number calibration. Here, we present an improved method for the microwave loss estimation inside of a closed cryogenic system. Our approach is based on Planck’s law and makes use of independent temperature sweeps of individual parts of the cryogenic setup. Using this technique, we can experimentally resolve changes in microwave losses of less than 0.1 dB in the cryogenic environment. We discuss potential applications of this approach for the precise characterization of quantum limited superconducting amplifiers and in other prominent experimental settings.

Published by the American Physical Society
2025
Toward a precision determination of the
X(6200)
parameters from data
Authors: Song Yi-Lin , Zhang Yu , Baru Vadim , Guo Feng-Kun , Hanhart Christoph , Nefediev Alexey
Published: February 2025

In a recent paper [], the LHCb data on the di-J/ψ production in proton-proton collisions were analyzed in a coupled-channel framework based on double-vector-charmonium channels. This investigation identified a robust pole near the J/ψJ/ψ threshold, tagged X(6200), suggesting it as a new state. The present work extends that investigation by incorporating recent di-J/ψ production data from the CMS and ATLAS Collaborations and performing a combined analysis of all three datasets. This study confirms the existence of the X(6200), and its pole position is now determined with a higher precision than in the previous study, where only a single dataset was employed. The pole corresponding to the X(6900) is also extracted, though its actual position and residue depend on a particular coupled-channel model employed and deviate from values reported in the experimental investigations. Moreover, we demonstrate that the currently available data do not allow one to determine whether there is an additional pole in the studied mass range. The dielectron width of the X(6200) is estimated under different conjectures on its quantum numbers, and the number of such states that can be annually produced at the future Super τ-Charm Facility is estimated. The line shape in the complimentary J/ψψ(2S) channel is discussed, and a good agreement with the ATLAS data is found.

Published by the American Physical Society
2025
Floquet evolution of the
q
-deformed
SU(3)1
Yang-Mills theory on a two-leg ladder
Authors: Hayata Tomoya , Hidaka Yoshimasa
Published: February 2025

We simulate Floquet time evolution of a truncated SU(3) lattice Yang-Mills theory on a two-leg ladder geometry under open boundary conditions using IBM’s superconducting 156-qubit device ibm_fez. To this end, we derive the quantum spin representation of the lattice Yang-Mills theory and compose a quantum circuit carefully tailored to hardware, reducing the number of controlled-Z gates. Since it is still challenging to simulate Hamiltonian evolution in present noisy quantum processors, we make the step size in the Suzuki-Trotter decomposition very large and simulate thermalization dynamics in Floquet circuit composed of the Suzuki-Trotter evolution. We demonstrate that IBM’s Heron quantum processor can simulate, by error mitigation, Floquet thermalization dynamics in a large system consisting of 62 qubits. Our work would be a benchmark for further quantum simulations of lattice gauge theories using real devices.

Published by the American Physical Society
2025
Identifying eccentricity in binary black hole mergers using a harmonic decomposition of the gravitational waveform
Authors: Patterson Ben G. , Tomson Sharon Mary , Fairhurst Stephen
Published: February 2025

We show that the gravitational waveform emitted by a binary on an eccentric orbit can be naturally decomposed into a series of harmonics. The frequencies of these harmonics depend upon the radial frequency, fr, determined by the time to return to apoapsis, and the azimuthal frequency, fϕ, determined by the time to complete one orbit relative to a fixed axis. These frequencies differ due to periapsis advance. Restricting to the (2, 2) multipole, we find that the frequencies can be expressed as f=2fϕ+kfr. We introduce a straightforward method of generating these harmonics and show that the majority of the signal power is contained in the k=−1,0,1 harmonics for moderate eccentricities. We demonstrate that by filtering these three leading harmonics, we are able to obtain a good estimate of the orbital eccentricity from their relative amplitudes.

Published by the American Physical Society
2025
Verification of the tenth-order QED contribution to the anomalous magnetic moment of the electron from diagrams without fermion loops
Authors: Aoyama Tatsumi , Hayakawa Masashi , Hirayama Akira , Nio Makiko
Published: February 2025

A discrepancy of approximately 5σ exists between the two known results for the tenth-order QED contribution to the anomalous magnetic moment of the electron, calculated from Feynman vertex diagrams without fermion loops. To investigate this, we decomposed this contribution into 389 parts based on a self-energy diagram representation, enabling a diagram-by-diagram numerical comparison of the two calculations. No significant discrepancies were found for individual diagrams. However, the numerical differences of the 98 diagrams sharing a common structure were not randomly distributed. The accumulation of these differences resulted in the 5σ discrepancy. A recalculation with increased statistics in the Monte Carlo integration was performed for these 98 diagrams. By replacing the old values with the new ones for these 98 integrals, we have obtained a revised result of 6.800±0.128, thereby resolving the discrepancy.

Published by the American Physical Society
2025
Successive phase transition in higher-order topological Anderson insulators
Authors: Li Aodong , Xu Bingcong , Xie Biye
Published: February 2025

Disorder, traditionally believed to hinder the propagation of waves, has recently been shown to prompt the occurrence of topological phase transitions. For example, when disorder strength continuously increases and surpasses a certain critical value, a transition from topologically trivial to nontrivial insulating phases can occur. However, in the nontrivial phase region, it remains unclear whether a finer phase diagram can be further classified by varying disorder strengths. Here, we present a successive topological phase transition driven by the disorder strength in a higher-order topological insulator with long-range couplings. As the disorder strength gradually increases, the real-space topological invariant of the system undergoes a consecutive change from 0 to 4, accompanied by a stepped increase in the number of boundary-localized corner states. Our work opens a pathway for utilizing disorder to induce phase transitions among different higher-order topological insulators.

Published by the American Physical Society
2025
Middle‐Aged Adults' Perspectives on Caregiving for Their Siblings With Intellectual and Developmental Disabilities
Authors: Hwang Se Kwang , Kim Kyung Mee , Lee Chung Eun
Published: February 2025

There is limited understanding of middle‐aged siblings' experiences of assuming caregiving roles and responsibilities in non‐Western cultures. This study explored middle‐aged siblings' perceived caregiving obligation for their siblings with intellectual and developmental disabilities within the South Korean societal framework that emphasizes the cultural value of “filial piety.” Data from in‐depth semi‐structured interviews with 13 middle‐aged siblings were thematically analyzed. The findings showed that middle‐aged siblings exhibit a strong urge to fulfill their filial duties and willingly embrace the primary caregiver role. However, gender, birth order, and financial responsibilities significantly influence the fulfillment of filial obligations, with older, male, and financially secure siblings who co‐reside with their siblings with disabilities being more likely to embrace caregiving roles. Despite advancements in South Korea's disability policies, the concept of caregiving as a familial duty rooted in filial piety remains unchanged. Future measures should consider individualized, culturally sensitive support for middle‐aged siblings.
Solid Lipid Nanoparticles Encapsulated With Paromomycin: An Effective Oral Formulation Against Leishmania major in Mouse Model
Authors: Heidari‐Kharaji Maryam , Rodrigues Priscilla , Petersen Christina
Published: February 2025

Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania. The treatment of intracellular infections such as leishmaniasis is often challenging due to limited drug access to infected cells and the development of drug resistance. Therefore, the development of new antileishmanial compounds is essential. Paromomycin sulphate (PM) has shown promise as an antileishmanial drug, and one way to enhance its effectiveness is through appropriate delivery systems. Solid lipid nanoparticles (SLN) are being explored as a potential delivery system for PM, as they offer advantages over other colloidal carriers. In a recent study, PM was loaded into solid lipid nanoparticles (PM‐SLN) and its oral effectiveness was evaluated in treating Leishmania (L.) major‐infected mice. The study measured footpad swelling, quantified parasite load through real‐time PCR and assessed levels of cytokines such as interleukin‐4 (IL‐4) and gamma interferon (IFN‐c), nitric oxide (NO) and Arginase (ARG). Overall, the study demonstrated that oral administration of the PM‐SLN formulation is safe and effective in treating leishmaniasis. The SLN in the PM‐SLN compound improved the killing of parasites by PM and stimulated a Th1 immune response, indicating its potential as a treatment for leishmaniasis.
Moral Dilemma Debates with Older Persons
Authors: De Souza Luciana Karine , Martínez Sophia Beylouni Santos , Pereira Milene Amaral , Fritzen Bruna Wagner , Bataglia Patrícia Unger Raphael , Gauer Gustavo
Published: February 2025

This research study and educational intervention aimed to foster ethical reasoning in older persons via systematic debates on moral dilemmas. We conducted an intervention via focus group with seven participants aged between 60 e 82 years old (six women and one man), all residing in Porto Alegre, Brazil. They participated in a 15-week intervention with 13 moral dilemma discussions. The first and the last group meeting were used for assessment (pre-test and post-test), with the Moral Competence Test and other measures. We gathered enough evidence that the intervention yielded positive results that fostered continued reflection on complex topics and the exercise of individual and group critical thinking. Results shed light on how moral competence, moral development after the age of 60, and universal and culture-specific moral issues are intertwined. This program has been requested to be offered regularly at the university.
Preventive Interventions Regarding Sexuality in Adolescence: A Systematic Review of School-Based Programs
Authors: De Azevedo Fernando Martins , Schnor Amanda Costa , Chaise Rodrigo Falcão , Jacobsen Gabriela dos Santos , Rocha Kátia Bones , Pizzinato Adolfo
Published: February 2025

This study describes preventive interventions in school-based settings aimed at reducing sexually transmitted infections (STIs) among adolescents. A systematic review was conducted. 3860 articles were identified, of which 25 were thoroughly analyzed. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Database searches using PsycNet, Scopus, and PubMed happened on May 27, 2020. MeSH terms were employed. The review was limited to articles published from January 1, 2016, to the search date. Inclusion criteria targeted original empirical studies on preventive interventions for school-age adolescents. The goal was to reach studies reporting school programs designed to work on adolescent sexuality, HIV, STIs, and sexual risk. Results indicate that most interventions significantly enhanced knowledge about HIV, STIs, and prevention. Notably, interventions with substantial behavioral outcomes (such as carrying a condom) covered a diverse range of topics. Gender, relationship equity, communication skills, decision-making, and violence are examples. It is possible to conclude the importance of a comprehensive approach to improving sexual health in adolescence.
Load Energy Coupling-Based Underactuated Control Method on Trajectory Planning and Anti-Swing for Bridge Cranes
Authors: Fan Bo , Zhao Yi , Zhou Hangyu , Wang Jianxiang , Sun Lifan
Published: February 2025

The closed-loop control methods of bridge crane systems adopt the real-time signal feedback to improve the performance of the systems. The energy-based closed-loop control method of bridge crane systems can be used to design the controller by constructing the energy function of the system, which avoids the direct analysis of the complex motion state of the systems and has the clear physical significance. However, the conventional energy-based control methods have some problems, including slow response, poor performance of eliminating pendulum and less parameters reflected by the control law. An novel load energy coupling-based underactuated control method for bridge cranes is proposed. The relationship between the energy of the bridge crane system and the energy of the load system is analyzed with the dynamic model of the two-dimensional bridge crane. The coupling function based on the load displacement and swing angle is constructed. The driving force of the system is obtained by Lyapunov method and the control law is designed. The boundedness and convergence of the closed-loop control system is explained by the principle of LaSalle invariance. With the comparison experiments and results analysis, it is shown that the proposed method can obtain the better performance of eliminating swing and realize the accurate positioning of the trolley. It also reflects this proposed method effectively reduces the dependence on model parameters and simplifies the control law.