bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Extrapulmonary Tuberculosis Among US Veterans, 1990–2022
Authors: Oda Gina , Lucero-Obusan Cynthia , Schirmer Patricia , Chung Joyce , Holodniy Mark
Published: November 2024

Purpose

To determine factors that put US veterans with active tuberculosis at risk for extrapulmonary tuberculosis (EPTB) compared with pulmonary tuberculosis.

Methods

We included veterans with laboratory-confirmed tuberculosis from 1990–2022 in our retrospective cohort study. Multivariable logistic regression was used to estimate the association of demographic and clinical risk factors with EPTB.

Results

Of 7493 veterans aged 20–100 years (median, 58 years) with laboratory-confirmed tuberculosis, 1397 (19%) had EPTB. The most common EPTB infection among veterans was pleural (31.4%), while meningitis carried the highest mortality risk at 90 days. Factors independently associated with EPTB among veterans were non-Hispanic black race/ethnicity, diabetes mellitus, human immunodeficiency virus infection, severe kidney disease, and all-cause mortality within 90 days after tuberculosis diagnosis.

Conclusions

Our study demonstrated several risk factors for EPTB among US veterans. Healthcare providers should be educated regarding patient populations at risk for EPTB, especially given the challenges in diagnosing this disease and the importance of instituting early treatment to prevent severe illness and death.
Assessment of the link between life purpose and health
Authors: Sias Richard , Turtle Harry J
Published: November 2024

Background

This study examined the temporal relations between a decline in health and changes in life purpose to better understand the causal direction between life purpose and morbidity.

Methods

Over a 16-year period, 7598 individuals completed up to four quadrennial surveys, which included information on 14 health metrics (lung function, grip strength, walking speed, balance and diagnoses of hypertension, diabetes, cancer, lung disease, heart condition, stroke, psychiatric problem, arthritis, dementia and Alzheimer’s) and life purpose. Ordinary and logistic regressions were used to examine the temporal relations between changes in purpose and changes in health over both the same 4-year period and over the subsequent 8 years.

Results

A decline in health was associated with a 5% standard deviation decline (95% confidence interval −0.08, −0.02) in purpose over the same 4-year period. In contrast, there was no evidence that a decline in purpose was associated with a subsequent decline in health.

Conclusions

The results fail to support the hypothesis that life purpose causes subsequent morbidity but support the hypothesis that a decline in health causes a decline in purpose. There is little evidence that life-purpose intervention policies will meaningfully impact subsequent morbidity.
A Survey of the Current UK Physician Associate Educator Workforce and Recommendations for Courses and Provider Organizations
Authors: Reeve Sarah , Gray James , Watkins Jeannie , Donaldson-Perrott Amy , Straughton Kate
Published: November 2024

Introduction

In the United Kingdom there are 37 physician associate (PA) training programs with limited knowledge of the educators involved, their training, and specific needs.

Method

An online questionnaire was sent to PA educators in all UK training programs requesting information on academic title and responsibilities, clinical and nonclinical background, education and qualifications before becoming a PA educator, formal and informal training received in the role, and insights into career progression.

Discussion

The questionnaire highlighted 5 specific areas that should be specific recommendations for UK training programs to support PA educators, alongside existing guidance. These centered on academic and leadership development, clinical engagement, student support, and pedagogical research.

Conclusion

We believe that implementing these recommendations across training programs will improve the opportunities for all those delivering PA education and consequently improve the offering to the students undertaking PA studies programmes.
Endoscopic management of colonic perforations
Authors: Sharma Prabin , Stavropoulos Stavros N.
Published: November 2024

Purpose of review

We will review the current management of colonic perforations, with particular emphasis on iatrogenic perforations caused by colonoscopy, the leading etiology. We will focus on recently developed endoscopic techniques and technologies that obviate morbid emergency surgery (the standard management approach in years past).

Recent findings

Colonic perforations are rare but potentially fatal complications of both diagnostic and therapeutic colonoscopy resulting in death in approximately 5% of cases with the mortality increasing with delay in diagnosis and treatment. As novel endoscopic techniques and tools have flourished in recent years, our approach to management of these perforations has evolved. With the availability of newer tools such as over the scope clips, enhanced through the scope clips and novel endoscopic suturing devices, colonic perforations can be managed effectively in many or most patients without the morbidity of surgical interventions.

With expanding use of colonoscopy, inadvertent outcomes such as perforations are bound to increase as well. Early diagnosis permits minimally invasive, nonsurgical, endoscopic management in most cases if the expertise and tools are available. Centers with high colonoscopy volumes including therapeutic procedures would be well served to invest in the requisite technologies and expertise.
Virucidal activity of olanexidine gluconate against SARS-CoV-2
Authors: Watanabe Rika , Yoshida Takuma , Nakaminami Hidemasa
Published: November 2024

Introduction: Antiseptics have been used for infection control against SARS-CoV-2. Ethanol (EtOH) was effective against SARS-CoV-2, while chlorhexidine gluconate (CHG) was less effective. Therefore, there may be differences in virucidal activity between classes of antiseptic agents.
Aim: In this study, we evaluated the efficacy of antiseptics against SARS-CoV-2 and identified effective agents for infection control.
Methods: The following antiseptics were used in this study: 1.5% olanexidine gluconate (OLG); 80% EtOH; 1% sodium hypochlorite (NaClO); 0.2% benzalkonium chloride (BKC); 1% povidone-iodine (PVP-I); 0.5%, 1%, and 1.5% chlorhexidine gluconate (CHG); and 0.5% alkyldiaminoethylglycine hydrochloride (AEG). Virucidal activity was evaluated at 0, 30 s, 1, 2, and 3 min according to EN14476.
Results: After 30 s of exposure, 1.5% OLG, 80% EtOH, 1% NaClO, 0.2% BKC, and 1% PVP-I inactivated SARS-CoV-2 below the detection limit. In contrast, the virus was survived in 0.5% CHG, 1% CHG, and 0.5% AEG after 3 min of exposure. However, the virucidal activity of 1.5% CHG was insufficient after 30 s of exposure.
Conclusion: This study showed that the virucidal activity against SARS-CoV-2 differs depending on the class of antiseptic agent. Despite belonging to the same class of biguanide antiseptics, OLG was more effective against SARS-CoV-2 than CHG.
Quantitative assessment of Candida albicans, Staphylococcus aureus and Staphylococcus epidermidis in peri-implant health and disease: correlation with clinical parameters
Authors: Fragkioudakis Ioannis , Konstantopoulos Georgios , Kottaridi Christine , Doufexi Aikaterini-Elisavet , Sakellari Dimitra
Published: November 2024

Introduction. Peri-implantitis poses a significant challenge in oral health due to its complex microbial profile and biofilm-related persistence, complicating both prevention and treatment strategies.

Hypothesis/Gap Statement. We hypothesized that biofilm formation by Candida albicans, Staphylococcus aureus and Staphylococcus epidermidis plays a critical role in peri-implantitis by inducing an inflammatory response, contributing to bone loss and implant failure. This study aimed to investigate the presence and quantify C. albicans, S. aureus and S. epidermidis in health and peri-implantitis using quantitative real-time PCR, enhancing our understanding of their roles in peri-implant disease.

Aim: To explore the microbial burden of C. albicans, S. aureus, and S. epidermidis in peri-implantitis and healthy conditions, correlating these findings with clinical parameters.

Methodology. In this cross-sectional study, 102 patients were recruited from the Department of Periodontology and Implant Biology at Aristotle University, Greece. Participants were divided into healthy/mucositis and peri-implantitis groups. Clinical parameters such as probing depth, clinical attachment levels and bleeding on probing were recorded, and microbiological samples were collected and analysed using real-time PCR, targeting specific genes for the pathogens.

Results. Results showed that C. albicans was detected in 3.92 and S. aureus in 9.82% of samples, while S. epidermidis was present in all samples, with significantly higher loads in the peri-implantitis group (404.75 copies µl−1) compared to the healthy/mucositis group (173.04 copies µl−1, P<0.001). Higher concentrations of S. epidermidis correlated with increased probing depth, clinical attachment levels and bleeding on probing.

Conclusions. The research strongly emphasizes the notable connection between S. epidermidis and peri-implantitis, indicating its potential impact on the development and progression of the condition. These findings underscore the significance of considering the quantity of S. epidermidis in clinical research aimed at effectively managing patients with peri-implant diseases.
Adaptive human behavior and delays in information availability autonomously modulate epidemic waves
Authors: Mahmud Md Shahriar , Eshun Solomon , Espinoza Baltazar , Kadelka Claus
Published: November 2024

The recurrence of epidemic waves has been a hall-mark of infectious disease outbreaks. Repeated surges in infections pose significant challenges to public health systems, yet the mechanisms that drive these waves remain insufficiently understood. Most prior models attribute epidemic waves to exogenous factors, such as transmission seasonality, viral mutations, or implementation of public health interventions. We show that epidemic waves can emerge autonomously from the feedback loop between infection dynamics and human behavior. Our results are based on a behavioral framework in which individuals continuously adjust their level of risk mitigation subject to their perceived risk of infection, which depends on information availability and disease severity. We show that delayed behavioral responses alone can lead to the emergence of multiple epidemic waves. The magnitude and frequency of these waves depend on the interplay between behavioral factors (delay, severity, and sensitivity of responses) and disease factors (transmission and recovery rates). Notably, if the response is either too prompt or excessively delayed, multiple waves cannot emerge. Our results further align with previous observations that adaptive human behavior can produce non-monotonic final epidemic sizes, shaped by the trade-offs between various biological and behavioral factors–namely, risk sensitivity, response stringency, and disease generation time. Interestingly, we found that the minimal final epidemic size occurs on regimes that exhibit a few damped oscillations. Altogether, our results emphasize the importance of integrating social and operational factors into infectious disease models, in order to capture the joint evolution of adaptive behavioral responses and epidemic dynamics.

Significance statement

We develop a behavioral-epidemiological framework in which individuals adjust their level of risk mitigation (e.g., social distancing, mask-wearing) based on both the available information and their perceived risk of infection. We show that the feedback loop between infectious disease dynamics and human behavior can autonomously produce multiple epidemic waves. The disease dynamics are strongly influenced by the interplay between the timing, severity and sensitivity of behavioral responses, as well as transmission and recovery rates. Moreover, our results confirm that adaptive human behavior can produce non-monotonic final epidemic sizes, which we show is due to oscillatory epidemic dynamics. Interestingly, we found that in the absence of interventions, the minimal final epidemic size occurs on regimes exhibiting a few damped oscillations.
Causal associations between niacin bluntness and schizophrenia: a GWAS and Mendelian randomization study
Authors: Sun Liya , Chen Fangyu , Li Mo , Liu Changchang , Jiang Jie , Dai Yuanyuan , Wang Jinfeng , Gao Yan , He Lin , Qin Shengying , Wan Chunling
Published: November 2024

Background and Hypothesis

Niacin skin bluntness is a promising biomarker for schizophrenia, especially in precision medicine, as it helps identify a distinct subgroup (around 1/3) of patients with schizophrenia who experience severe functional impairment. However, research has not clarified if this phenotype is just a byproduct of the onset of the disease or is involved in the etiology of schizophrenia. We hypothesize that niacin bluntness reflects causal alterations in schizophrenia.

Study Design

We firstly conducted a quasi-genome-wide association analysis within schizophrenia patients to identify instrumental SNPs for niacin response. Then a two-sample bi-directional Mendelian randomization (MR) analysis was implemented to estimate the potential causal effects between niacin response and schizophrenia.

Study Results

25 independent SNPs showed a trend of genome-wide significant association (p<E-05) with niacin response in schizophrenia. In the MR analysis, the F statistics of the two instrumental SNPs for niacin response is 30.77, indicating a proper strength. As heterogeneity of the SNPs was detected (p<0.05), the result of inverse variance weighted method for multiplicative random effects was adopted for evaluation of the detected causal effect (OR=1.272, p=9.46E-03). In reverse MR analysis, none of the methods supported a causal effect of schizophrenia on niacin response (all p>0.05).

Conclusions

Our results revealed that the attenuated niacin response caused schizophrenia but not vice versa. Etiological studies on niacin bluntness in schizophrenia are needed and will pave the way for biomarker-guided personalized treatment in future.
Shortwave infrared imaging increases the number of lymph nodes and the number of positive lymph nodes in surgical pathology specimens – a 104-patient study
Authors: Jorns J M , Smith R S , Strenk D , Stauble G , Khelifa S , Seltzer R , Manuel J , Rosenbaum M W , Almas J , Li Z
Published: November 2024

Aims

Adequate lymph node examination is key to accurate cancer staging. Lymph node search in surgical resection specimens is a challenging task because it can be labor intensive and inconsistent. This study investigates the effectiveness of shortwave infrared imaging technology in increasing the overall and positive lymph node numbers.

Methods

104 surgical resection specimens from two hospitals were first grossed with traditional manual palpation. The residual tissues were then grossed with the assistance of shortwave infrared imaging. The numbers of lymph nodes and positive lymph nodes within these two steps were documented and compared.

Results

In 90 of the 104 cases (86.5%), shortwave infrared imaging assisted gross examination identified additional lymph nodes. In 11 of 104 cases (10.6%), shortwave infrared imaging assisted gross examination identified additional positive lymph nodes.

Conclusions

Shortwave infrared imaging increases the number of lymph nodes and the number of positive lymph nodes in surgical pathology specimens compared to traditional visual and manual dissection.
A Cross-Sectional Survey of Knowledge, Attitudes and Practices (KAP) towards COVID-19 in working professionals of Islamabad during lockdown
Authors: Nisar Nadia , Haider Murtaza Haider , Yaqoob Aashifa , Safdar Inayah , Badar Nazish
Published: November 2024

Background

The first confirmed case of COVID-19 in Pakistan was reported on 26 February 2020. Along with several other regions, Islamabad was affected by COVID-19 epidemic. Smart lockdown was declared on 23 March 2020 in Islamabad. The purpose of the survey was to study the status of Knowledge, Attitude and Practice regarding COVID-19 among the government employees, residing in Islamabad city, during COVID-19 outbreak.

Methods

A week during smart lockdown, a cross sectional survey was conducted in Islamabad city between 5th to 19thMay 2020. Sociodemographic of participants were compared with one way, t-test, or Chi-square test. Data analysis was conducted using SPSS version 24.0.

Results

A total of 775 participants completed the survey. Among this final sample, average age was 24 years. Among the survey participants, 455 (59%) were men, 444 (had bachelor’s degree, 364(47%) had monthly income between Pakistani Rupees (PKR) 25,000 to 60,000, and 483 (62%) were married. The overall correct response rate of knowledge was 73.2%. The score in COVID-19 negative attitude was highest. 455 males reported handwashing. Majority (89%) had prior knowledge regarding COVID-19 clinical symptoms. The 71% showed their confidence in ability for Pakistan to control COVID-19 outbreak. 87% avoided reducing outdoor activities.

Conclusion

The study findings suggest that residents of Islamabad city have adequate levels of knowledge regarding COVID-19. However, it is paramount to introduce awareness campaigns and public health education to promote the knowledge and practice of COVID-19 disease.
Challenges in Implementing a Mobile AI Chatbot Intervention for Depression Among Youth on Psychiatric Waiting Lists: A Randomized Control Study Termination Report
Authors: Fujita Junichi , Yano Yuichiro , Shinoda Satoru , Sho Noriko , Otsuki Masaki , Suda Akira , Takayama Mizuho , Moroga Tomoko , Yamaguchi Hiroyuki , Ishii Mio , Miyazaki Tomoyuki
Published: November 2024

Background

The mental health of children and adolescents is a growing public health concern, with increasing rates of depression and anxiety impacting their emotional, social, and academic well-being. In Japan, access to timely psychiatric care is limited, leading to extended waiting periods that can range from three months to a year. AI-driven chatbots, such as emol, which integrate Acceptance and Commitment Therapy (ACT), show potential as digital solutions to support young patients during these waiting times. The AI chatbot emol was selected based on a comprehensive review of Japanese mental health technology applications, including in-person evaluations with company representatives.

Objective

This exploratory, parallel-group randomized controlled trial examined the feasibility of using AI chatbot emol with pediatric and adolescent individuals on psychiatric waiting lists.

Methods

Participants aged 12-18 years were recruited from four hospitals in Kanagawa Prefecture and randomly assigned to either an intervention group, receiving eight weekly chatbot sessions, or a control group, receiving standard mental health information. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) scores from pre- to post-intervention. Secondary assessments, such as voice and writing pressure analysis, provided additional engagement metrics, with data collected at baseline, during the intervention, and at week 9.

Results

Of the 96 eligible individuals on psychiatric waiting lists, eight expressed interest, and three provided initial consent. However, all participants subsequently withdrew or were excluded, resulting in no evaluable data for analysis. Low engagement may have been influenced by the perceived irrelevance of digital tools, complex protocols, and privacy concerns.

Conclusions

Significant barriers to engagement suggest that digital interventions may need simpler protocols and trusted environments to improve feasibility. Future studies could test these interventions in supportive settings, like schools or community centers, to enhance accessibility and participation among youth.

Trial Registration

Japan Registry of Clinical Trials (jRCT) jRCT1032230427
Extreme weather events in the UK and resulting public health outcomes
Authors: Dickinson Natalie , Spencer Llinos Haf , Yang Shuhua , Miller Caroline , Hursthouse Andrew , Lynch Mary
Published: November 2024

Objectives

Extreme Weather Events (EWEs) are increasingly frequent in the UK and can lead to adverse physical and mental health outcomes which may result in additional pressure on the NHS. The objective of this study is therefore to investigate the health impacts of EWEs on the population in the UK.

Method

A systematic review of the evidence was conducted. Seven databases were searched for studies related to the public health outcomes of EWEs.

Results

48 papers met the criteria for inclusion (22 flood, 25 extreme temperature, 1 wind). Flooding is most associated with mental health concerns and associated social effects, whilst temperature extremes impact more on physical health.

Conclusions

Whilst there is a great deal of research on the physical and mental health impacts of EWEs in the UK, there is limited evidence on social health impacts, and little consideration of the economic costs of holistic health outcomes. Building resilience against the health impacts of EWEs is essential. Future studies should consider incorporating cost-benefit analyses (CBA) to investigate the economic costs of EWEs on populations and health systems in the UK.
Expression of recombinant human glutamylating TTLLs in human cells leads to differential tubulin glutamylation patterns, with only TTLL6 disrupting microtubule dynamics
Authors: Al Kabbani Mohamed Aghyad , Jatoo Pragya , Klebl Kathrin , Klebl Bert M. , Zempel Hans
Published: November 2024

Polyglutamylation, a post-translational modification (PTM) catalyzed by a subset of Tubulin Tyrosine Ligase-Like (TTLL) family enzymes, regulates microtubule dynamics through its influence on interactions with microtubule-associated, motor, and severing proteins, and has recently also been implicated in genetic and neurodegenerative diseases. In this study, we characterized the glutamylation activity of various glutamylating TTLLs in human embryonic kidney 293T (HEK293T) cells, revealing distinct patterns of mono- and polyglutamylation among TTLL family members, with TTLL4 and TTLL11 exhibiting the strongest chain initiation and elongation activities, respectively. We found that TTLL6 expression uniquely decreased microtubule stability, with live-cell imaging of end-binding protein (EB3) showing a TTLL6-induced decrease in microtubule stability. To explore therapeutic modulation of TTLL activity, we tested LDC10, a novel TTLL inhibitor, which successfully blocked glutamylation across all TTLLs investigated in this study, while also reversing the microtubule-destabilizing effects of TTLL6. These findings identify a potential pathogenic role of TTLL6 in microtubule dynamics and highlight LDC10 as a promising pharmacological tool to counteract TTLL-induced microtubule destabilization.
Susceptibility to inflammatory bowel diseases promotes invasive carcinomas in a murine model of ATF6-driven colon cancer
Authors: Kövilein Janine , Sorbie Adam , Khaloian Sevana , Küntzel Vanessa , Ahmed Mohamed , Jarosch Sebastian , Remke Marianne , Metwaly Amira , Reuss Elena M. , Busch Dirk , Allez Matthieu , Steiger Katja , Schraml Barbara , Coleman Olivia I , Haller Dirk
Published: November 2024

Chronic inflammation in inflammatory bowel disease (IBD) patients represents a risk factor for developing colitis-associated cancer (CAC). We previously linked the endoplasmic reticulum unfolded protein response (UPRER) signal transducer activating transcription factor 6 (ATF6) with spontaneous microbiota-dependent colonic adenoma development in mice expressing epithelial-specific activated ATF6 (nATF6IEC). To investigate IBD-related risk factors in ATF6-mediated tumorigenesis, we crossed tumor-free monoallelic (tg/wt) nATF6IEC mice with Interleukin-10 deficient mice (Il10-/-). IL10 deficiency initiated tumor susceptibility, with 77% of 12-week tg/wt;Il10-/- mice developing colonic adenomas and invasive carcinomas in this novel CAC mouse model. Tumor formation correlated with mucosal immune cell infiltration, characterized by CD11b+ granulocytes and monocytes, and mucosa-associated dysbiosis. Colonization of germ-free nATF6IEC;Il10-/- mice with minimal biosynthetic consortia and IBD stool re-established CAC, confirming microbiota-dependent ATF6-driven tumorigenesis. Increased ATF6 expression in IBD patients during active disease highlights its human relevance. Our findings show that IBD susceptibility heightens the risk for ATF6-driven tumorigenesis.
Eosinophils promote monocyte to macrophage differentiation and anti-bacterial immunity
Authors: Wilson Gillian J , Foley Lily Koumbas , Pocalun Zuzanna , Pitmon Elise , Fukuoka Ayumi , Lee Kit M , Fernandez Lauren , Mathie Heather , Bartolini Robin , Cole John J. , Graham Gerard J
Published: November 2024

Chemokine receptors control cell migration within the body. Here we reveal a novel interaction between eosinophils and monocytes in the bone marrow, indirectly controlled by the atypical chemokine receptor ACKR2. We demonstrate that ACKR2 maintains eosinophil levels within the bone marrow by scavenging CCL11. In the absence of ACKR2, elevated CCL11 leads to increased egress of eosinophils from the bone marrow into the bloodstream. As a result, eosinophil and monocyte interactions are reduced within the bone marrow niche, leading to changes in monocyte gene expression. Monocytes from ACKR2-/- mice are recruited to the tissues but are fundamentally altered in their ability to differentiate into macrophages, in the lung, peritoneal cavity and cavity wall. Bacterial elimination is impaired in ACKR2-/- mice during peritoneal infection. ACKR2 is therefore a key regulator of eosinophil-driven monocyte education in the bone marrow, required for full monocyte differentiation and macrophage function within the tissues.
Reduced regulatory complexity associated with the evolutionary transition to sociality from cockroaches to termites despite evolutionary parallels with Hymenoptera
Authors: Jones Alun R.C. , Dohmen Elias , Berger Juliette , Legendre Frédéric , Harrison Mark , Bornberg-Bauer Erich
Published: November 2024

In social species, the phenotypic diversity within a single species has often been associated with more complex genetic regulation. Transcription factors (TFs) being key to genetic regulation, have been studied in the origins of eusociality in Hymenoptera (Bees, Ants and Wasps) but less so in Blattodea (Cockroaches and Termites). Here we show that the social transition in Blattodea, from cockroaches to termites, displays similar patterns of regulatory change to those found in Hymenoptera. Specifically, by analysing 3 cockroach and 5 termite genomes, we find more TF families with relaxed selection compared to intensified selection and lineage-specific gene family expansions in termites. We also find that genes under selection support neotenic caste determination. There are key differences in TF regulation in comparison with Hymenoptera with contractions in TF gene families and reduced diversity in enriched DNA binding motifs of TFs.

Furthermore, we show that with increased social complexity TF activating domain diversity, one of the evolutionary and structural building blocks of TFs, decreases with gene family size while DNA binding domain diversity and number increases. This study highlights similarities in social transitions between Hymenoptera and Blattodea, with evidence of large changes in transcriptional regulation followed by lineage specific adaptations. We also show that phenotypic diversity in termites does not necessitate greater transcriptional complexity.
Stepwise Assembly Of Crown Reptile Anatomy Clarified By Late Paleozoic Outgroups Of Neodiapsida
Authors: Jenkins Xavier A. , Benson Roger B. J. , Ford David P. , Browning Claire , Fernandez Vincent , Dollman Kathleen , Gomes Timothy , Griffiths Elizabeth , Choiniere Jonah N. , Peecook Brandon R.
Published: November 2024

Living reptiles include more than 20,000 species with disparate ecologies. Direct anatomical evidence from Neodiapsida, which includes the reptile crown-group Sauria and its closest extinct relatives, shows that this diversity originates from a single common reptilian ancestor that lived some 255 million years ago in the Paleozoic. However, the evolutionary assembly of crown reptile traits is poorly understood due to the lack of anatomically close outgroups to Neodiapsida1–7. We present a substantially revised phylogenetic hypothesis, informed by new anatomical data derived from high-resolution synchrotron tomography of Paleozoic reptiles8–12. We find strong evidence placing the clade Millerettidae as a close sister to Neodiapsida, which uniquely share a suite of derived features among Paleozoic stem reptiles. This grouping, for which we name the new clade Parapleurota, replaces previous phylogenetic paradigms by rendering the group Parareptilia as a polyphyletic assemblage of stem reptiles, of which millerettids are the most crownward. Our analysis presents hypotheses that resolve long-standing issues in Paleozoic reptile evolution, including the placement of captorhinids on the amniote stem lineage and firm support for varanopids as synapsids, which taken together provide a greatly improved fit to the observed stratigraphic record. Optimizations of character evolution on our phylogenetic hypothesis reveals gradual assembly of crown reptile anatomy, including a Permian origin of tympanic hearing, the presence of a lower temporal fenestra in the amniote common ancestor, with subsequent modifications on the reptile stem lineage, leading to the loss of the lower temporal bar. This evolutionary framework provides a platform for investigating the subsequent radiations of the reptile crown group in the Early Triassic, including the lines leading to dinosaurs (including birds), crocodilians, lepidosaurs, and extinct marine reptiles.
Shaping the developing homunculus: the roles of deprivation and compensatory behaviour in sensory remapping
Authors: Tucciarelli Raffaele , Bird Laura , Straka Zdenek , Szymanska Maggie , Kollamkulam Mathew , Sonar Harshal , Paik Jamie , Clode Danielle , Hoffmann Matej , Cowie Dorothy , Makin Tamar R.
Published: November 2024

Some of the most dramatic examples of neuroplasticity in the human brain follow congenital sensory deprivation, though we have limited understanding of the plasticity mechanisms driving such large-scale remapping. Hand loss due to congenital limb differences (CLD) offers a unique temporal dissociation of developmental neuroplasticity mechanisms: While sensory deprivation is congenital, compensatory motor behaviours develop progressively across childhood. Using paediatric neuroimaging and semi-ecological behavioural analysis in children (5-7 years old) and adults (>25 years old) with unilateral upper-limb CLD, we studied deprivation- and use-dependent plasticity in the deprived primary somatosensory cortex and beyond. We reveal that global remapping, encompassing the entire sensory homunculus, is established early and maintained in adulthood. We demonstrate that deprivation-driven homeostatic plasticity can drive this global remapping, with Hebbian-based compensatory learning further contributing to inter-individual differences both in childhood and adulthood. Our findings emphasise the early establishment and stability of cortical maps, despite extensive daily-life behavioural adaptation.
Impaired spatial coding and neuronal hyperactivity in the medial entorhinal cortex of agedAppNL-G-Fmice
Authors: Rodriguez Gustavo A. , Rothenberg Eva F. , Shetler C. Oliver , Aoun Andrew , Posani Lorenzo , Vajram Srujan V. , Tedesco Thomas , Fusi Stefano , Hussaini S. Abid
Published: November 2024

The progressive accumulation of amyloid beta (Aβ) pathology in the brain has been associated with aberrant neuronal network activity and poor cognitive performance in preclinical mouse models of Alzheimer’s disease (AD). Presently, our understanding of the mechanisms driving pathology-associated neuronal dysfunction and impaired information processing in the brain remains incomplete. Here, we assessed the impact of advanced Aβ pathology on spatial information processing in the medial entorhinal cortex (MEC) of 18-monthAppNL-G-F/NL-G-Fknock-in (APP KI) mice as they explored contextually novel and familiar open field arenas in a two-day, four-session recording paradigm. We tracked single unit firing activity across all sessions and found that spatial information scores were decreased in MEC neurons from APP KI mice versus those in age-matched C57BL/6J controls. MEC single unit spatial representations were also impacted in APP KI mice. Border cell firing preferences were unstable across sessions and spatial periodicity in putative grid cells was disrupted. In contrast, MEC border cells and grid cells in Control mice were intact and stable across sessions. We then quantified the stability of MEC spatial maps across sessions by utilizing a metric based on the Earth Mover’s Distance (EMD). We found evidence for increased instability in spatially-tuned APP KI MEC neurons versus Controls when mice were re-exposed to familiar environments and exposed to a novel environment. Additionally, spatial decoding analysis of MEC single units revealed deficits in position and speed coding in APP KI mice in all session comparisons. Finally, MEC single unit analysis revealed a mild hyperactive phenotype in APP KI mice that appeared to be driven by narrow-spiking units (putative interneurons). These findings tie Aβ-associated dysregulation in neuronal firing to disruptions in spatial information processing that may underlie certain cognitive deficits associated with AD.
Neural Mechanisms of Intersensory Switching: Evidence for Delayed Sensory Processing and Increased Cognitive Effort
Authors: Vanneau Theo , Quiquempoix Michael , Foxe John J. , Molholm Sophie
Published: November 2024

Intersensory switching (IS), the ability to shift attention between different sensory systems, is essential for cognitive flexibility, yet leads to slower responses compared to repeating the same sensory modality. The underlying neural mechanisms of IS remain largely unknown. In this study, high-density EEG was used to investigate these mechanisms in healthy adults (n=53) performing a speeded reaction time (RT) task involving visual and auditory stimuli. Trials were categorized as Repeat (same preceding modality) or Switch (different preceding modality). Switch trials showed slower RTs and delayed sensory responses (N1 and P2 components). Furthermore, across both Repeat and Switch trials, RT correlated with the latency of these neural responses. Additionally, lower alpha-band inter-trial phase coherence (ITPC) in primary sensory regions was noted for Switch compared to Repeat trials, suggesting reduced efficiency of sensory processing. Greater induced theta activity over fronto-central scalp regions in Switch trials suggested increased cognitive control demands, potentially involving the anterior cingulate cortex (ACC). These findings reveal that IS is characterized by delayed sensory processing and heightened cognitive load, supporting a model where prior stimulus primes the sensory cortex for faster processing in Repeat trials, while Switch trials demand more cognitive resources for adjustment. The similarity of effects across both auditory and visual sensory modalities suggests that IS effects represent core features of sensory processing, potentially reflecting a fundamental, modality-independent mechanism of attentional switching across sensory domains.
Enterococcal cell wall remodelling underpins pathogenesis via the release of the Enteroccocal Polysaccharide Antigen (EPA)
Authors: Smith Robert E , Christena Rene L , Michno Bartosz J , Davis Jessica L , Lidbury Ian DEA , Alaman-Zarate Marcel , Stefanidi Danai , Maes Emmanuel , Fisher Hannah , Prajsnar Tomasz K , Mesnage Stéphane
Published: November 2024

Enterococci are opportunistic pathogens displaying a characteristic ovoid shape, typically forming pairs of cells (diplococci) and short chains. Control of cell chain length in Enterococci is critical during pathogenesis for dissemination in the host and to limit recognition by innate immune effectors such as complement molecules and phagocytes. Here, we identify AtlE, an N-acetylmuramidase responsible for peptidoglycan hydrolysis-mediated septum cleavage during stationary phase. AtlE is encoded by the locus required to produce the decoration subunits of the Enterococcal Polysaccharide Antigen (EPA), which mediate evasion of phagocytosis. We show that peptidoglycan hydrolysis by AtlE is essential for pathogenesis and demonstrate that soluble cell wall fragments containing EPA decorations increase the virulence ofEnterococcus faecalis, suggesting that EPA plays a role as a decoy molecule to evade host defences. This research sheds light on the complex interplay between bacterial cell division, cell wall remodelling, and the host immune system, providing valuable insights into a novel mechanism underlying the virulence ofE. faecalis.
Behavioral and Neural Correlates of Temperament Traits: Insights from Temperament and Character Inventory and fMRI-Based Choice Tasks
Authors: Sisara Majid Abbasi , Hosseini Seyed Hamid Khodadad , Mahjoub Hossein , Kordnaeij Asadollah , Esmaeilinasab Maryam
Published: November 2024

A cognitive conflict that is negatively arousing and results in a divergence in preference attitudes toward the chosen and rejected alternatives occurs when individuals are compelled to choose between alternatives that are similarly preferable. This phenomenon, which is frequently referred to as “cognitive dissonance,” is of interest in the fields of decision neuroscience and psychology. This study examines the behavioral and neural underpinnings of Cloninger’s temperament traits—Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS)—in a decision-making context.Functional magnetic resonance imaging (fMRI) and a modified free-choice paradigm were used to formalize the effect of Cloninger temperaments on cognitive conflict induced by choice. Behavioral analysis revealed significant individual differences across the four TCI dimensions, highlighting distinct variability in participants’ responses. Imaging data showed that participants with the highest and lowest scores in each temperament trait exhibited unique brain activation patterns during difficult and easy decision tasks. Notably, novelty-seeking was linked to heightened activation in brain regions associated with exploration and cognitive flexibility, while harm avoidance was associated with emotional processing and conflict detection. These findings provide deeper insights into how personality traits influence both behavior and neural responses during cognitive dissonance and decision-making tasks, offering implications for understanding individual differences in decision-related behaviors. The results of this study confirm the effect of temperaments on the degree of perceived dissonance of people, which can be used in many areas such as consumer behavior in marketing. The reason for this is the hesitancy of customers after purchasing the products.

Significance Statement

This study provides novel insights into how Cloninger’s temperament traits—Novelty Seeking, Harm Avoidance, Reward Dependence, and Persistence—modulate both neural and behavioral responses during decision-making processes. By combining fMRI with a modified free-choice paradigm, we reveal that temperament traits significantly impact cognitive dissonance, with distinct brain activation patterns corresponding to individual differences in decision conflict. These findings enhance our understanding of the neural basis of cognitive dissonance and have practical implications for areas such as consumer behavior, where temperament-driven decision conflict can influence post-purchase attitudes. This research highlights the importance of accounting for personality traits when examining decision-related behaviors and suggests that tailoring strategies based on temperament could improve decision outcomes in various applied fields.
Polarized ATP synthase in synaptic mitochondria induced by learning and plasticity signals
Authors: Hu Yi , Wang Xi , Liu Kaiyuan , Xiong Songhai , Guan Ji-Song , Xie Hong , Gu Min
Published: November 2024

MINFLUX represents a state-of-the-art single-molecule localization microscopy technology that surpasses the conventional diffraction limit, enabling the visualization and analysis of nanostructures with exceptional precision. Despite its potential, the utilization of MINFLUX has been primarily confined to in vitro cultured cell environments. In this research, we have refined the sample preparation protocols to facilitate 3D MINFLUX imaging in fixed brain tissue sections, focusing on the mitochondrial distribution within dendritic spines and engram cells of the dentate gyrus. Probing single moleculesin vivoreveals an interesting finding: the reorganization of mitochondrial inner membrane proteins during synaptic plasticity within dendritic spines of engram cells. Utilizing 3D MINFLUX nanoscopy, we identified a significant redistribution of α-F1-ATP synthase, which correlates with learning related activities. This redistribution implies a pivotal function for polarized ATP synthesis in the vicinity of the postsynaptic zone, which may modulate both short-term and long-term synaptic modifications, thereby influencing synaptic plasticity and memory consolidation. Furthermore, dual-color 3D MINFLUX imaging has uncovered distinct patterns of mitochondrial reorganization involving both the inner and outer membranes within dendritic spines. These patterns, induced by plasticity signals, persist for up to 12 hours in neuronal cultures. This distinction highlights the presence of distinct regulatory mechanisms governing mitochondrial proteins during synaptic plasticity. These results offer new insights into the molecular mechanisms underlying synaptic plasticity and underscore the transformative potential of 3D MINFLUX imaging for studying neuronal processes in the brain.
NaviNIBS: a comprehensive and open-source software toolbox for neuronavigated noninvasive brain stimulation
Authors: Cline Christopher C. , Forman Lily , Hartford Winn , Truong Jade , Parmigiani Sara , Keller Corey J.
Published: November 2024

Image-guided positioning, or neuronavigation, is critical for precise targeting of transcranial magnetic stimulation (TMS) and other noninvasive brain stimulation. However, existing commercial systems have limitations in flexibility and extensibility for research applications. We present new open-source software for neuronavigated non-invasive brain stimulation (NaviNIBS) that provides comprehensive functionality for TMS experiments. NaviNIBS supports imaging data import, target planning, head registration, real-time tool tracking, and integration with robotic positioning and electrophysiology systems. Key features include flexible target specification, support for multiple tracking hardware options, refined head registration techniques, and an extensible addon system. We describe the software architecture, core functionality, characterization of tracking performance, and example applications of NaviNIBS. This software aims to facilitate methodological improvements and novel experimental paradigms in noninvasive brain stimulation research.
Quantifying information stored in synaptic connections rather than in firing patterns of neural networks
Authors: Fan Xinhao , Mysore Shreesh P
Published: November 2024

A cornerstone of our understanding of both biological and artificial neural networks is that they store information in the strengths of connections among the constituent neurons. However, in contrast to the well-established theory for quantifying information encoded by the firing patterns of neural networks, little is known about quantifying information encoded by its synaptic connections. Here, we develop a theoretical framework using continuous Hopfield networks as an exemplar for associative neural networks, and data that follow mixtures of broadly applicable multivariate log-normal distributions. Specifically, we analytically derive the Shannon mutual information between the data and singletons, pairs, triplets, quadruplets, and arbitrary n-tuples of synaptic connections within the network. Our framework corroborates well-established insights about storage capacity of, and distributed coding by, neural firing patterns. Strikingly, it discovers synergistic interactions among synapses, revealing that the information encoded jointly by all the synapses exceeds the 'sum of its parts'. Taken together, this study introduces an interpretable framework for quantitatively understanding information storage in neural networks, one that illustrates the duality of synaptic connectivity and neural population activity in learning and memory.
CalliCog:an open-source cognitive neuroscience toolkit for freely behaving nonhuman primates
Authors: Scott Jack T. , Mendivez Vasquez Bruno L. , Stewart Brian J. , Panacheril Dylan D. , Rajit Darren K. J. , Fan Angela Y. , Bourne James A.
Published: November 2024

Nonhuman primates (NHPs) are pivotal for unlocking the complexities of human cognition, yet traditional cognitive studies remain constrained to specialized laboratories. To revolutionize this paradigm, we presentCalliCog: an open-source, scalable in-cage platform tailored for freely behaving experiments in small primate species such as the common marmoset (Callithrix jacchus).CalliCogincludes modular operant chambers that operate autonomously and integrate seamlessly with home cages, eliminating human intervention. Our results showcase the power ofCalliCogto train experimentally naïve marmosets in touchscreen-based cognitive tasks. Remarkably, across two independent facilities, marmosets achieved touchscreen proficiency within two weeks and successfully completed tasks probing behavioral flexibility and working memory. Moreover,CalliCogenabled precise synchronization of behavioral data with electrocorticography (ECoG) recordings from freely moving animals, opening new frontiers for neurobehavioral research. By makingCalliCogopenly accessible, we aim to democratize cognitive experimentation with small NHPs, narrowing the translational gap between preclinical models and human cognition.

Motivation

Cognitive neuroscience research involving nonhuman primates (NHPs) has traditionally been confined to a few highly specialized laboratories equipped with advanced infrastructure, expert knowledge, and specialized resources for housing and testing these animals. The common marmoset (Callithrix jacchus), a small NHP species, has gained popularity in cognitive research due to its ability to address some of these challenges. However, behavioral studies in marmosets remain labor-intensive and restricted mainly to experts in the field, making them less accessible to the broader scientific community. To address these barriers, we introduce an open and accessible platform designed for automated cognitive experiments in home cage settings with marmosets. This system supports the integration of cognitive behavioral analysis with wireless neural recordings, is cost-effective, and requires minimal technical expertise to build and operate.