bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher Levels of Multiple Types of Stress Are Associated With Worse State Anxiety and Morning Fatigue Profiles in Patients Receiving Chemotherapy
Authors: Garcia Philip , Block Astrid , Mark Sueann , Mackin Lynda , Paul Steven M. , Cooper Bruce A. , Conley Yvette P. , Hammer Marilyn J. , Levine Jon D. , Miaskowski Christine
Published: January 2024

Background

Anxiety and fatigue are common problems in patients receiving chemotherapy. Unrelieved stress is a potential cause for the co-occurrence of these symptoms.

Objectives

The aims of this study were to identify subgroups of patients with distinct state anxiety and morning fatigue profiles and evaluate for differences among these subgroups in demographic and clinical characteristics, as well as measures of global, cancer-specific, and cumulative life stress and resilience and coping.

Methods

Patients (n = 1335) completed measures of state anxiety and morning fatigue 6 times over 2 cycles of chemotherapy. All of the other measures were completed prior to the second or third cycle of chemotherapy. Latent profile analysis was used to identify the state anxiety and morning fatigue profiles.

Results

Three distinct joint profiles were identified: Low Anxiety and Low Morning Fatigue (59%), Moderate Anxiety and Moderate Morning Fatigue (33.4%), and High Anxiety and High Morning Fatigue (7.6%). Patients in the 2 highest classes were younger, were less likely to be married/partnered, and had a higher comorbidity burden. All of the stress scores demonstrated a dose-response effect (ie, as anxiety and morning fatigue profiles worsened, stress increased). Patients in the 2 highest classes reported higher rates of emotional abuse, physical neglect, physical abuse, and sexual harassment.

Conclusions

More than 40% of these patients experienced moderate to high levels of both anxiety and morning fatigue. Higher levels of all 3 types of stress were associated with the 2 highest profiles.

Implications for Practice

Clinicians need to perform comprehensive evaluations of patients’ levels of stress and recommend referrals to psychosocial services.
Spotlight on Leadership
Authors: Fontenot Justin
Published: January 2024

Artificial intelligence (AI) is not a new concept. Since the 2022 release of a popular large language model, AI has become readily accessible to the general population, brought transformational shifts in healthcare, and created significant implications for nurse leaders. Specifically, AI has major indications in the area of evidence-based practice. Historically, new evidence takes years to reach the bedside. Nurse leaders are instrumental in closing the research-to-practice gap and, in doing so, promote optimal patient safety and care delivery methods. This article provides an overview of using AI in the context of nursing leadership in healthcare settings, including appropriate case use. In addition, this article covers the ethical challenges of using AI in clinical settings.
Autopsy-Based Comparative Study of Gross and Histopathological Findings at Bone Fracture Surfaces Before and After Death
Authors: Moirangthem Sangita , Arora Arneet , Vidua Raghvendra Kumar , Goel Garima
Published: January 2024

Fractures of bones are commonly encountered in traumatic injuries, and distinguishing between antemortem (AM) and postmortem (PM) bone fractures is crucial for estimating the time since injury and has important medicolegal implications. Correct differentiation enables understanding the dynamics of the injury and, in some cases, the cause of death. The present study aims to evaluate the gross morphological and histopathological characteristics of bony fracture surfaces to determine whether they occurred before or after an individual's death.

Fifty-seven sets of bone samples, including both antemortem and artificially created postmortem fractures, were collected from cadavers during medicolegal autopsies, meeting the inclusion criteria. Gross morphological and histopathological features were examined after staining the bony fracture edges with hematoxylin and eosin stain. The study revealed distinct morphological characteristics at fracture surfaces for both antemortem and artificially created postmortem fractures. In addition, signs of vital reaction were observed exclusively in antemortem fracture cases.

In conclusion, the findings emphasize the importance of meticulous morphological and histopathological examination of bony fracture surfaces to differentiate between antemortem fractures and artificially created postmortem artifacts. This differentiation holds significant value in forensic investigations and medicolegal cases.
Traditional Lecture Versus Procedural Video Randomized Trial: Comparative Analysis of Instructional Methods for Teaching Baclofen Pump Management
Authors: Weppner Justin , Conti Andrea , Locklear Tonja M. , Mayer Robert Samuel
Published: January 2024

Objective

This study compared the effectiveness of traditional lectures and micro-videos in teaching baclofen pump programming and refilling to physicians who have completed less than ten refills for the previous two years.

Design

A mixed-method approach was employed with 60 participating physicians specializing in physical medicine & rehabilitation or pain management. Pre- and post-intervention assessments were conducted using a rubric, and the participants’ perceptions and preferences were gathered through focus group sessions.

Results

Two-thirds of the participants specialized in physical medicine & rehabilitation. No significant differences in the pre-intervention, post-intervention, or knowledge retention scores were found between the traditional lecture and micro-video groups. Both methods demonstrated comparable effectiveness in improving the baclofen pump refilling and programming skills. Qualitatively, participants perceived both approaches as equally helpful, but those in the micro-video group raised concerns owing to instructors’ unavailability and online platform navigation. Nevertheless, they preferred the convenience, accessibility, and time-efficiency of the micro-videos.

Conclusions

The study concluded that micro-videos are an effective alternative to traditional lectures for acquiring knowledge on baclofen pump programming and refilling. Further research should consider learners’ characteristics and investigate the benefits of blended learning in medical education.
The development of cancer nutrition research from 2013 to 2022: a bibliometric and visualized analysis study
Authors: Zhang Chuying , Zhang Gege , Wu Tiantian , Fida Saba , Zhou Mingming , Song Chunhua
Published: January 2024

Background:

The use of nutrition in cancer treatment has become increasingly widespread in recent decades, and the current stage of nutritional support and assessment has had a positive effect on reducing the side effects of cancer treatment. Based on the analysis of international literature on “tumor nutrition,” we identified the current status of research, research hotspots, and frontiers and provided a theoretical basis and reference for the development of related research in China. This study aimed to conduct a bibliometric analysis of the global literature published from 2013 to 2022 to assess the current research directions.

Methods:

The Web of Science core collection was searched from 2013 to 2022. The VOSviewer 1.6.19 and CiteSpace 6.2.2 were adopted to conduct the analysis.

Results:

Following the inclusion and exclusion criteria, a total of 28,245 documents were collected. The number of articles issued annually was fluctuatingly increasing. These articles were written by 124,412 authors from 20,162 affiliations in 166 countries or regions and were published in 3110 journals. The leading authors were Susan M. Gapstur, Heiner Boeing, and Hanping Shi. All publications were taken from 166 countries/regions and 20,162 organizations. The most productive countries were the United States and China. The most active institutions were the Harvard Medical School and University of Alberta. A total of 3110 journals contributed to this field, and the leading journals were Nutrients and Clinical Nutrition. The important author keywords occurred most frequently were cancer, nutrition, risk, survival, mortality, and sarcopenia.

Conclusions:

This study provided the dynamics and progress of nutrition research field. The studies about nutrition are booming. The current growth trend predicts that the global field of oncology nutrition will still increase. In addition to the traditional research on tumor nutrition, the development of interdisciplinary research should be promoted. Every country should strengthen international cooperation to enhance the influence of research results and solve many common scientific problems in the field of tumor nutrition research in multiple dimensions.
Vitamin E and risk of first stroke in general hypertensive patients: a nested case–control study
Authors: Siddiqi Sultan Mehmood , Chen Ping , Li Shuqun , Wei Yaping , He Qiangqiang , Zhou Ziyi , Xu Jiafeng , Bai Jie , Liu Lishun , Wang Binyan , Xu Xiping , Qin Xianhui , Mehmood Anam , Yiming Du , Song Yun , Zhang Zhijie
Published: January 2024

Background:

Epidemiological studies on the association between levels of plasma vitamin E and first stroke risk are inconclusive.

Methods:

A nested, case–control study was conducted utilizing data on 115,337 hypertensive patients from the H-type Hypertension and Stroke Prevention and Control Project. The current analysis comprised 2193 cases of first stroke and 2193 controls matched for age, sex, and study site.

Results:

The mean plasma concentration of vitamin E was 12.37 (3.61) μg/mL. The smoothing curve showed a linear correlation between plasma vitamin E levels and the risk of the first stroke. Hypertensive patients with plasma vitamin E levels ≥14.1 μg/mL (Q4) had an increased risk of first stroke (adjusted odds ratios [OR]: 1.18; 95% confidence interval [CI]: 1.01, 1.37) compared with those with plasma vitamin E < 14.1 μg/mL (Q1–Q3). Sub-group analysis revealed that the relationship between plasma vitamin E (≥14.1.1 vs. P interaction = 0.035).

Conclusions:

This study suggests that higher levels of plasma vitamin E are associated with an elevated risk of first stroke among Chinese hypertensive patients.
Utility of Enteral Contrast Protocols in Pediatric Adhesive Small Bowel Obstruction
Authors: Acker Shannon N. , Ignacio Romeo , Russell Katie W. , Kelley-Quon Lorraine , Lofberg Katrine , Lee Justin , Jensen Aaron R. , Pickett-Nairne Kaci , Prendergast Connor , Iantorno Stephanie E. , Thangarajah Hari , Patwardhan Utsav , Melhado Caroline , Zhong Allen , Padilla Ben , Rothstein David H. , Nicassio Lauren , Pandya Samir , Valencia Maria , Wang Kasper , Inge Tom H. ,   on behalf of the Western Pediatric Surgery Research Consortium
Published: January 2024

Objective:

Our objective was to determine the utility of enteral contrast-based protocols in the diagnosis and management of adhesive small bowel obstruction (ASBO) for children.

Background:

Enteral contrast-based protocols for adults with ASBO are associated with decreased need for surgery and shorter hospitalization. Pediatric-specific data are limited.

Methods:

We conducted a prospective observational study between October 2020 and December 2022 at nine children’s hospitals who are members of the Western Pediatric Surgery Research Consortium. Inclusion criteria were children aged 1-20 years diagnosed with ASBO who underwent a trial of nonoperative management (NOM) at hospital admission. Comparisons were made between those children who received an enteral contrast challenge and those who did not. The primary outcome was need for surgery.

Results:

We enrolled 136 children (71% male; median age: 12 y); 84 (62%) received an enteral contrast challenge. There was no difference in rate of operative intervention between the no contrast (34.6%) and contrast groups (36.9%; P=0.93). Eighty-seven (64%) were successfully managed nonoperatively with no difference in median length of stay (P=0.10) or rate of unplanned readmission (P=0.14). Among the 49 children who required an operation, there was no significant difference in time from admission to surgery or rate of small bowel resection based on prior contrast administration.

Conclusions:

The addition of enteral contrast-based protocols for management of pediatric ASBO does not decrease the likelihood of surgery or shorten hospitalization. Larger randomized studies may be needed to further define the role of radiologic contrast in the management of ASBO in children.
Centralization of Pancreaticoduodenectomy
Authors: Kotecha Krishna , Tree Kevin , Ziaziaris William A. , McKay Siobhan C. , Wand Handan , Samra Jaswinder , Mittal Anubhav
Published: January 2024

Objective:

Through a systematic review and spline curve analysis, to better define the minimum volume threshold for hospitals to perform (pancreaticoduodenectomy) and the high volume centre (HVC).

Summary Background Data:

The pancreaticoduodenectomy (PD) is a resource intensive procedure, with high morbidity and long hospital stays resulting in centralization towards high-volume hospitals; the published definition of high-volume remains variable.

Materials and Methods:

Following a systematic review of studies comparing PD outcomes across volume groups, semiparametric regression modelling of morbidity (%), mortality (%), length of stay (days), lymph node harvest (number of nodes) and cost ($USD) as continuous variables was performed and fitted as a smoothed function of splines. If this showed a non-linear association, then a “zero-crossing” technique was used which produced “first and second derivatives” to identify volume thresholds.

Results:

Our analysis of 33 cohort studies (198,377 patients) showed 55 PDs/year and 43 PDs/year were the threshold value required to achieve lowest morbidity and highest lymph node harvest, with model estimated degrees of freedoms

5.154 (P<0.001) and 8.254 (P<0.001) respectively. The threshold value for mortality was approximately 45 PDs/year (model

9.219 (P <0.001)) with the lowest mortality value (the optimum value) at approximately 70 PDs/year (i.e. a high volume centre). No significant association was observed for cost (e.d.f=2, P=0.989), and length of stay (e.d.f=2.04, P=0.099).

Conclusions:

There is a significant benefit from centralization of PD, with 55 PDs/year and 43 PDs/year the threshold value required to achieve lowest morbidity and highest lymph node harvest respectively. To achieve mortality benefit, the minimum procedure threshold is 45 PDs/year, with the lowest and optimum mortality value (i.e. a high volume center) at approximately 70 PDs/year.
The American Society of Transplant Surgeons Consensus Statement on Normothermic Regional Perfusion
Authors: Wall Anji E. , Adams Bradley L. , Brubaker Aleah , Chang Cherylee W.J. , Croome Kristopher P. , Frontera Jennifer , Gordon Elisa , Hoffman Jordan , Kaplan Lewis J. , Kumar Deepali , Levisky Josh , Miñambres Eduardo , Parent Brendan , Watson Christopher , Zemmar Ajmal , Pomfret Elizabeth A.
Published: January 2024

On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.
Immunomodulatory options for neurodevelopmental spectrum conditions: are we there yet?
Authors: Arenella Martina
Published: January 2024

About 3–7% of the worldwide population is diagnosed with a neurodevelopmental condition, including autism and attention-deficit hyperactivity disorder. Nonetheless, the aetiology of these conditions is unclear and support options are limited or not effective for all those diagnosed. Cumulating evidence, however, supports a role of the immune system in neurodevelopment, and immune dysregulations have been implicated in neurodevelopmental atypicalities. This knowledge offers tremendous opportunities, especially the possibility to adopt immunomodulatory compounds, which are already available and safe to use, for the management of neurodevelopmental difficulties. This perspective discusses the potential of immune-based interventions in neurodevelopmental care. Here, the application of existing immunomodulatory compounds to symptom management is justified by findings of immune dysregulations across neurodevelopmental conditions and preliminary, encouraging immune-based clinical trials. Still, key considerations are presented, specifically the necessity of immune biomarkers to ensure the right support option for the right (subgroup of) individuals within the neurodevelopmental spectrum.
Autoprot: Processing, Analysis and Visualization of Proteomics Data in Python
Authors: Bender Julian , Mühlhäuser Wignand W. D. , Zimmerman Johannes P. , Drepper Friedel , Warscheid Bettina
Published: January 2024

Motivation

The increasing numbers of complex quantitative mass spectrometry-based proteomics data sets demand a standardised and reliable analysis pipeline. For this purpose, Python-based analysis, particularly through Jupyter notebooks, serves as a simple yet powerful tool. Nevertheless, the availability of Python software for standardised and accessible MS data analysis is limited, and this software is often constrained to using analysis functions written in Python. This excludes existing and well-tested software, for example written in R. Despite this, Python offers several interactive data visualisation modules that greatly enhance exploratory research and facilitate result communication with collaboration partners. Consequently, there is a need for an integrated and Jupyter-compatible Python analysis pipeline that incorporates R algorithms and interactive visualization for proteomics data analysis.

We developed autoprot, a Python module for simplified analysis of quantitative mass spectrometry-based proteomics experiments processed with the MaxQuant software. It provides access to established functions written in both Python and R for statistical testing and data transformation. Moreover, it generates JavaScript-based interactive plots that can be integrated into interactive web applications. Thereby, autoprot offers standardised, fast and reliable proteomics data analysis while maintaining the high customisability required to tailor the analysis pipeline to specific experiments.

Availability and Implementation

Autoprot is implemented in Python ≥ 3.9 and can be downloaded fromhttps://github.com/ag-warscheid/autoprot. Online documentation is available athttps://ag-warscheid.github.io/autoprot/.
Preliminary Survey of Fungal Communities Across a Plastics/No Plastics Transition on an Oregon Beach
Authors: Cullings Ken , Arterbury Karisa Boyce , Arterbury Richard
Published: January 2024

Plastics pose an increasing and significant threat to both human and environmental health. While many fungi can degrade a variety of organic polymers, investigations into which fungi possess the potential to remediate environmental plastics contamination have only recently become a priority. To help address this need, we tested the null hypothesis that chronic plastics contamination has no impact on the fungal communities across a plastics/no plastics transition in a beach sand in northern Oregon. We used sieving and binocular microscopy of microplastics (particle size, 12.6µm +/-5.5µm, detection range 1-5000µm) to confirm the plastics/no plastics transition. We used paired plot design to collect samples across this transition and analyzed the fungal communities using high-throughput DNA sequencing methods for fungal ITS-2. Results indicated that the beach sand contaminated with plastics held an extensive fungal community, while un-contaminated sand held no fungal community at all. System dominants includedAcremoniumandPenicillium, both free-living ascomycete fungi that have shown plastics-degrading capabilities in lab studies, and the ectomycorrhizal genus,Russulaa symbiotic fungus that has known plastics-degrading enzyme capabilities. Also amongst dominant genera was a human fungal pathogen (genusMalassezia) that causes chronic skin disease. These results provide new fungal models for further studies of fungal and ectomycorrhizal remediation of plastics contaminated contaminated beach sand.
Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories
Authors: Frigon Eve-Marie , Gérin-Lajoie Amy , Dadar Mahsa , Boire Denis , Maranzano Josefina
Published: January 2024

Background

Brain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous work in mice showed that two gross-anatomy laboratory solutions, a saturated-salt-solution (SSS) and an alcohol-formaldehyde-solution (AFS), preserve antigenicity of the main cellular markers. Our goal is now to compare the quality of histology and antigenicity preservation of human brains fixed with NBF by immersion (practice of brain banks) vs. those fixed with a SSS and an AFS by whole body perfusion, practice of gross-anatomy laboratories.

Methods

We used a convenience sample of 42 brains (31 males, 11 females; 25-90 years old) fixed with NBF (N=12), SSS (N=13), and AFS (N=17). One cm3tissue blocks were cut, cryoprotected, frozen and sliced into 40 μm sections. The four cell populations were labeled using immunohistochemistry (neuronal-nuclei (NeuN), glial-fibrillary-acidic-protein (GFAP), ionized-calcium-binding-adaptor-molecule1 (Iba1) and myelin-proteolipid-protein (PLP)). We qualitatively assessed antigenicity and cell distribution, and compared the ease of manipulation of the sections, the microscopic tissue quality, and the quality of common histochemical stains (e.g., Cresyl violet, Luxol fast blue, etc.) across solutions.

Results

Sections of SSS-fixed brains were more difficult to manipulate and showed poorer tissue quality than those from brains fixed with the other solutions. The four antigens were preserved, and cell labeling was more often homogenous in AFS-fixed specimens. NeuN and GFAP were not always present in the NBF and SSS samples. Some antigens were heterogeneously distributed in some specimens, independently of the fixative, but an antigen retrieval protocol successfully recovered them. Finally, the histochemical stains were of sufficient quality regardless of the fixative, although neurons were more often paler in SSS-fixed specimens.

Conclusion

Antigenicity was preserved in human brains fixed with solutions used in human gross-anatomy (albeit the poorer quality of SSS-fixed specimens). For some specific variables, histology quality was superior in AFS-fixed brains. Furthermore, we show the feasibility of frequently used histochemical stains. These results are promising for neuroscientists interested in using brain specimens from anatomy laboratories.
Effects of a school-based physical activity implementation program to reduce musculoskeletal pain frequency in children aged 9 to 12: a randomised clinical trial
Authors: Viana da Silva Priscilla , Kamper Steven J , Yamato Tiê Parma , Wolfenden Luke , Sutherland Rachel , McCarthy Nicole , Nolan Erin , Oldmeadow Christopher , Nathan Nicole , Williams Christopher M
Published: January 2024

Objective

To estimate the effect of scheduling physical activity during the school day on pain outcomes (frequency, severity, and impact), quality of life, physical activity and sedentary time in school children with musculoskeletal pain.

Design, setting, and participants

A preplanned secondary analysis of a cluster randomised trial in private elementary schools from Australia. Eligible participants were students aged 9 to 12 (grades 4 to 6) who reported having previous MSK pain.

Interventions

Intervention schools received support to increase the scheduling of physical activity during the school day (with and without nutrition strategies). Control schools received either support to implement nutrition strategies or no active support.

Main outcomes and measures

Pain frequency reported at 9-months after randomisation over the last six months. Secondary outcomes: quality of life (PedsQL 4.0), pain severity (FSP-R), physical activity and sedentary times, the prevalence of recent pain, and pain-related impact on physical activity, usual activities, school absenteeism, and health care utilisation.

Results

We included 633 students (mean age 10.5 years). Of those, 33% of students reported previous frequent pain at follow-up. We found no difference in pain frequency between groups (OR 1.0, 95% CI: 0.6 to 1.6). The intervention group had slightly higher physical activity levels (mean difference: 3.1 min/day, 95% CI: −0.02 to 6.2) and lower pain impact in usual activities (OR 0.7, 95% CI: 0.4 to 1.0).

Conclusion and relevance

Increased scheduling of physical activity in schools did not improve pain outcomes in children with MSK pain. However, results suggest that children can improve physical activity levels during school time despite experiencing pain.

Trial registration

ACTRN12616001228471

SUMMARY BOX

What is already known on this topic

Musculoskeletal (MSK) pain is prevalent among children and adolescents. The relationship between physical activity and pain is complex, with evidence indicating that physical inactivity can contribute to MSK pain, but pain may also serve as a barrier to engaging in physical activities.

What this study adds

We found that scheduling physical activity during school time did not improve pain outcomes of school-aged children with MSK pain. However, there appears to be a small benefit to improving physical activity levels and impact on usual activities in students with prior MSK pain.

How this study might affect research, practice or policy

This study highlights that children with MSK pain might need a more comprehensive approach to school-based physical activity programs, combining strategies that not only promote physical activity but also address the unique challenges posed by MSK pain in this age group.
A Dynamical Systems Approach to Optimal Foraging
Authors: Chaturvedi Siddharth , El-Gazzar Ahmed , Gerven Marcel van
Published: January 2024

Foraging for resources in an environment is a fundamental activity that must be addressed by any biological agent. Modelling this phenomenon in simulations can enhance our understanding of the characteristics of natural intelligence. In this work, we present a novel approach to model foraging in-silico using a continuous coupled dynamical system. The dynamical system is composed of three differential equations, representing the position of the agent, the agent’s control policy, and the environmental resource dynamics. Crucially, the control policy is implemented as a parameterized differential equation which allows the control policy to adapt in order to solve the foraging task. Using this setup, we show that when these dynamics are coupled and the controller parameters are optimized to maximize the rate of reward collected, adaptive foraging emerges in the agent. We further show that the internal dynamics of the controller, as a surrogate brain model, closely resemble the dynamics of the evidence accumulation mechanism, which may be used by certain neurons of the dorsal anterior cingulate cortex region in non-human primates, for deciding when to migrate from one patch to another. We show that by modulating the resource growth rates of the environment, the emergent behaviour of the artificial agent agrees with the predictions of the optimal foraging theory. Finally, we demonstrate how the framework can be extended to stochastic and multi-agent settings.

Author Summary

Intelligence is a phenomenon that arises due to the interactions of an agent’s dynamics with the environment’s dynamics under the assumption that the agent seeks optimization of certain objective. Modelling both these dynamics as a single coupled dynamical system can shed light on patterns of intelligence that unfold in time. This report aims to provide a minimal in-silico framework that models the main components involved in natural phenomena, like optimal foraging, as a coupled dynamical system. Interestingly, we observe similarities between the surrogate brain dynamics of the artificial agent with the evidence accumulation mechanism that can be responsible for decision-making in certain non-human primates performing a similar foraging task. We also observe similarities between trends prescribed by theories prevalent in behavioural ecology such as the optimal foraging theory and those shown by the artificial agent. Such similarities can increase the predictability and explainability of artificial systems. We can now expect them to mimic these natural decision-making mechanisms by replicating such trends and we can thus understand the reasoning behind their actions. They can also increase the confidence of researchers to consider using such artificial agent models as simulation tools to make predictions and test hypotheses about aspects of natural intelligence.
Spreading depolarization causes reversible neuronal mitochondria fragmentation and swelling in healthy, normally perfused neocortex
Authors: Sword Jeremy , Fomitcheva Ioulia V. , Kirov Sergei A.
Published: January 2024

Mitochondrial function is tightly linked to their morphology, and fragmentation of dendritic mitochondria during noxious conditions suggests loss of function. In the normoxic cortex, spreading depolarization (SD) is a phenomenon underlying migraine aura. It is unknown whether mitochondria structure is affected by normoxic SD.In vivotwo-photon imaging followed by quantitative serial section electron microscopy (ssEM) was used to monitor dendritic mitochondria in the normoxic cortex of urethane-anesthetized mature male and female mice during and after SD initiated by focal KCl microinjection. Structural dynamics of dendrites and their mitochondria were visualized by transfecting excitatory, glutamatergic neurons of the somatosensory cortex with bicistronic AAV, which induced tdTomoto labeling in neuronal cytoplasm and mitochondria labeling with roGFP. Normoxic SD triggered a rapid fragmentation of dendritic mitochondria alongside dendritic beading, both reversible; however, mitochondria took significantly longer to recover. Several rounds of SD resulted in transient mitochondrial fragmentation and dendritic beading without accumulating injury, as both recovered. SsEM corroborated normoxic SD-elicited dendritic and mitochondrial swelling and transformation of the filamentous mitochondrial network into shorter, swollen tubular and globular structures. Our results revealed normoxic SD-induced disruption of the dendritic mitochondrial structure that might impact mitochondrial bioenergetics during migraine with aura.
WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration
Authors: Coulter Alyssa M , Cortés Valerie , Theodore Corey J , Cianciolo Rachel E , Korstanje Ron , Campellone Kenneth G
Published: January 2024

The actin cytoskeleton is essential for many functions of eukaryotic cells, but the factors that nucleate actin assembly are not well understood at the organismal level or in the context of disease. To explore the function of the actin nucleation factor WHAMM in mice, we examined howWhamminactivation impacts kidney physiology and cellular proteostasis. We show that male WHAMM knockout mice excrete elevated levels of albumin, glucose, phosphate, and amino acids, and display abnormalities of the kidney proximal tubule, suggesting that WHAMM activity is important for nutrient reabsorption. In kidney tissue, the loss of WHAMM results in the accumulation of the lipidated autophagosomal membrane protein LC3, indicating an alteration in autophagy. In mouse fibroblasts and human proximal tubule cells, WHAMM and its binding partner the Arp2/3 complex control autophagic membrane closure and cargo receptor recruitment. These results reveal a role for WHAMM-mediated actin assembly in maintaining kidney function and promoting proper autophagosome membrane remodeling.
Evolution of a bistable genetic system in fluctuating and non-fluctuating environments
Authors: Fernández-Fernández Rocío , Olivenza David R. , Weyer Esther , Singh Abhyudai , Casadesús Josep , Sánchez-Romero María Antonia
Published: January 2024

Epigenetic mechanisms can generate bacterial lineages capable of spontaneously switching between distinct phenotypes. Currently, mathematical models and simulations propose epigenetic switches as a mechanism of adaptation to deal with fluctuating environments. However, bacterial evolution experiments for testing these predictions are lacking. Here, we exploit an epigenetic switch inSalmonella enterica,theopvABoperon, to show clear evidence that OpvAB bistability persists in changing environments but not in stable conditions. Epigenetic control of transcription in theopvABoperon produces OpvABOFF(phage-sensitive) and OpvABON(phage-resistant) cells in a reversible manner and may be interpreted as an example of bet-hedging to preadaptSalmonellapopulations to the encounter with phages. Our experimental observations and computational simulations illustrate the adaptive value of epigenetic variation as evolutionary strategy for mutation avoidance in fluctuating environments. In addition, our study provides experimental support to game theory models predicting that phenotypic heterogeneity is advantageous in changing and unpredictable environments.
Structure-Guided Mutagenesis Targeting Interactions between pp150 Tegument Protein and Small Capsid Protein Identify Five Lethal and Two Live Attenuated HCMV Mutants
Authors: Stevens Alex , Cruz-cosme Ruth , Armstrong Najealicka , Tang Qiyi , Zhou Z. Hong
Published: January 2024

Human cytomegalovirus (HCMV) replication relies on a nucleocapsid coat of the 150kDa, subfamily-specific tegument phosphoprotein (pp150) to regulate cytoplasmic virion maturation. While recent structural studies revealed pp150-capsid interactions, the role of specific amino-acids involved in these interactions have not been established experimentally. In this study, pp150 and the small capsid protein (SCP), one of pp150’s binding partners found atop the major capsid protein (MCP), were subjected to mutational and structural analyses. Mutations to clusters of polar or hydrophobic residues along the pp150-SCP interface abolished viral replication, with no replication detected in mutant virus-infected cells. Notably, a single point mutation at the pp150-MCP interface significantly attenuated viral replication, unlike the situation of pp150-deletion mutation where capsids degraded outside host nuclei. These functionally significant mutations targeting pp150-capsid interactions, particularly the pp150 K255E replication-attenuated mutant, can be explored to overcome the historical challenges of developing effective antivirals and vaccines against HCMV infection.
TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in ALS/FTD and related disorders
Authors: Arnold Frederick J. , Cui Ya , Michels Sebastian , Colwin Michael R. , Stockford Cameron , Ye Wenbin , Tam Oliver H. , Menon Sneha , Situ Wendy G. , Ehsani Kean C. K. , Howard Sierra , Hammell Molly Gale , Li Wei , La Spada Albert R.
Published: January 2024

Nuclear clearance and cytoplasmic aggregation of the RNA-binding protein TDP-43 are observed in many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and fronto- temporal dementia (FTD). Although TDP-43 dysregulation of splicing has emerged as a key event in these diseases, TDP-43 can also regulate polyadenylation; yet, this has not been adequately studied. Here, we applied the dynamic analysis of polyadenylation from RNA-seq (DaPars) tool to ALS/FTD transcriptome datasets, and report extensive alternative polyadenylation (APA) upon TDP-43 alteration in ALS/FTD cell models and postmortem ALS/FTD neuronal nuclei. Importantly, many identified APA genes highlight pathways implicated in ALS/FTD pathogenesis. To determine the functional significance of APA elicited by TDP-43 nuclear depletion, we examined microtubule affinity regulating kinase 3 (MARK3). Nuclear loss of TDP-43 yielded increased expression of MARK3 transcripts with longer 3’UTRs, resulting in greater transcript stability and elevated MARK3 protein levels, which promotes increased neuronal tau S262 phosphorylation. Our findings define changes in polyadenylation site selection as a previously unrecognized feature of TDP-43-driven disease pathology in ALS/FTD and highlight a potentially novel mechanistic link between TDP-43 dysfunction and tau regulation.
Birth of new protein folds and functions in the virome
Authors: Nomburg Jason , Price Nathan , Doudna Jennifer A.
Published: January 2024

Rapid virus evolution generates proteins essential to infectivity and replication but with unknown function due to extreme sequence divergence1. Using a database of 67,715 newly predicted protein structures from 4,463 eukaryotic viral species, we found that 62% of viral proteins are evolutionarily young and lack homologs in the Alphafold database2,3. Among the 38% of more ancient viral proteins, many have non-viral structural homologs that revealed surprising similarities between human pathogens and their eukaryotic hosts. Structural comparisons suggested putative functions for >25% of unannotated viral proteins, including those with roles in the evasion of innate immunity. In particular, RNA ligase T- (ligT) like phosphodiesterases were found to resemble phage-encoded proteins that hydrolyze the host immune-activating cyclic dinucleotides 3’3’ and 2’3’ cyclic G-A monophosphate (cGAMP). Experimental analysis showed that ligT homologs encoded by avian poxviruses likewise hydrolyze 2’3’ cGAMP, showing that ligT-mediated targeting of cGAMP is an evolutionarily conserved mechanism of immune evasion present in both bacteriophage and eukaryotic viruses. Together, the viral protein structural database and analytics presented here afford new opportunities to identify mechanisms of virus-host interactions that are common across the virome.
Evaluating Climate Warming Effects on Soil Resistome and Pathogenome: Future Risks for Agriculture and Human Health
Authors: Zhang Zhiguo , Ju Feng
Published: January 2024

How climate change affects the collection of antibiotic resistance genes (ARGs), called resistome, is a critical question for environmental and human health. By scrutinizing the dynamics of soil resisomes in a six-year (2014-2019) climate change experiment, this study provides explicit insights into the risk of antibiotic resistance in cropland and grassland microbiomes under future climate scenarios. Extreme summers (+2.2° and -35.4% soil moisture during 2018-2019) significantly shifted the resistomic composition of soil bacteria, resulting in a prominent increase in abundance of ARGs (copy/cell) conferring resistance to novobiocin (52.7%-72.8%), tetracycline (32.5%-53.0%) and vancomycin (31.5%-62.9%. Importantly, simulated warming (+0.6° and -9.1% soil moisture) significantly increased the proportion of mobilizable ARGs, possibly resulting from the warming-induced SOS response of soil microbes. In contrast, extreme summers decreased the mobility potential by dramatically filtering the hosts (e.g., γ-Proteobacteria) of mobilizable ARGs. Besides resistome conditioning, climate warming and extreme summers also disrupt the ecological balance of soil microbiome, offering a worrisome competitive advantage for specific soil-dwelling antibiotic-resistant phytopathogens (Clavibacter michiganensis and Rhodococcus fascians) and human pathogens (e.g., Staphylococcus aureus, Mycobacterium tuberculosis, Streptococcus pneumoniae and Listeria monocytogenes). This worrisome advantage will increase the likelihood of outbreaks of particular plant and human infectious diseases, resulting in significant economic losses and severe threats to human health worldwide. Overall, our findings emphasize the importance of surveilling soil resistomes and pathogens under future climate scenarios.
A neural correlate of learning fails to predict foraging efficiency inBombus terrestris
Authors: Pasquier Grégoire , Pull Christopher D. , Ott Swidbert R. , Leadbeater Ellouise
Published: January 2024

The mushroom bodies (MB) are integrative structures in the insect brain that, in social bees, contribute to both visual and olfactory learning. Changes in the density of presynaptic boutons (or microglomeruli) within the calyx region of the MB have been repeatedly linked to various aspects of foraging, including forms of learning that are thought to be key to support foraging efficiency. Here we set out to directly test the relationship between foraging efficiency and microglomerulus density in a bumblebee model,Bombus terrestris.We found no evidence that microglomerulus density predicted real-world foraging performance, nor any relationship with foraging experience. Instead, our data suggest a potential non-linear relationship between individual age, independent of foraging experience, and microglomerulus density in the lip region of the calyx, which is associated with olfactory processing. Our findings suggest that in real-world scenarios there is no simple direct relationship between microglomerular density, learning ability and foraging efficiency in bumblebees, highlighting the gap in knowledge regarding the relationships between learning abilities, neuroanatomy and foraging efficiency.
Encoding of task regularities links grid-like signals to human timing behavior
Authors: Polti Ignacio , Nau Matthias , Kaplan Raphael , van Wassenhove Virginie , Doeller Christian F.
Published: January 2024

Grid cells have been proposed to encode task regularities that allow predicting future states. Entorhinal grid-like signals might therefore mirror behavioral biases associated with relying on task regularities, like regression-to-the-mean biases in time estimation. Here, we tested this proposal using functional magnetic resonance imaging and a rapid timing task in humans. Indeed, trial-wise entorhinal activity reflected task accuracy and the degree to which interval estimates regressed towards the mean of all tested intervals. Grid-like signals were observed exclusively for the interval closest to the mean, which was explained by differences in temporal stability across intervals. Finally, both behavioral and entorhinal results were explained by a Bayesian observer model that assumes the integration of current-trial sensory evidence with prior expectations. Together, we find that entorhinal activity and grid-like signals reflect behavioral performance in a timing task, supporting the proposed role of grid cells in encoding task structure for predictive coordination of behavior.
Bleomycin induced EBV-specific gastric epithelial cell death is enhanced by LMP2A
Authors: Wai Aung Phyo , Azzahra Ahmad Wadi Afifa Fatimah , Liu Yuxin , Zolzaya Tumurgan , Okada Shunpei , Iizasa Hisashi , Yoshiyama Hironori
Published: January 2024

Epstein-Barr virus (EBV) infects more than 90% of the global population, leading to EBV-related cancers, such as EBV-associated gastric cancer and nasopharyngeal carcinoma. Despite the rarity of p53 mutations in tumor cells, there is a lack of specific therapies targeting EBV-associated gastric cancers. Our study demonstrated that EBV-infected gastric epithelial cells exhibited high sensitivity to the bleomycin family, encompassing bleomycin and zeocin, compared to uninfected cells. Zeocin treatment induces a DNA damage response (DDR) and promotes the expression of BZLF1, triggering the expression of EBV lytic genes. This cascade leads to apoptosis via a p53 dependent pathway, coinciding with the activation of caspase-3. Cells infected with the BZLF1-deficient virus could not induce apoptosis by zeocin treatment, and the cells maintained a tight latent infection but initiated a robust DDR. Conversely, neither lytic infection nor DDR was induced by zeocin treatment in cells infected with LMP2A-deficient virus. These findings indicate that LMP2A augments DDR in EBV-infected gastric epithelial cells, facilitating the transition from latent to lytic infection, and consequently inducing cell death. Bleomycin derivatives are expected to serve as fundamental components in the development of specific anticancer drugs targeting EBV-positive epithelial cancer cells.

IMPORTANCE

Because of its ubiquitous infection in the human population, the number of patients suffering from EBV-related diseases, including malignant tumors and severe active infections, is substantial. Previous research has reported the potential of drugs such as HDAC inhibitors and poly ADP-ribose polymerase inhibitors to induce cell death in EBV-infected cells. However, a clinical therapeutic agent specifically reducing EBV-infected cells has not yet been available. In this study, we report that bleomycin, or its derivative, which has been used for over half a century, induces apoptotic cell death in EBV-infected cells by triggering lytic viral replication associated with DNA damage response. Particularly, we discovered that the viral latent gene LMP2A unexpectedly enhances bleomycin-induced EBV-infected epithelial cell death by promoting DDR.
Quantitative reconstruction of atomic orbital densities of neon from partial cross sections
Authors: Kirschner Hans , Gottwald Alexander , Soltwisch Victor , Richter Mathias , Puschnig Peter , Moser Simon
Published: January 2024

The approach of photoemission orbital tomography, i.e., the orbital density reconstruction from photoemission of planar molecular layers by using a formalism equivalent to a Fourier transformation, is transferred to free atoms. Absolute radial orbital densities of neon 1s, 2s, and 2p orbitals are reconstructed with a central-field one-electron model, using well-known atomic photoionization data. The model parameters are optimized by a Markov chain Monte Carlo method with Bayesian inference from which uncertainties for the reconstructed orbital densities are derived. The presented model opens the path for photoemission orbital tomography as a powerful tool, as well as for a quantitative analysis.

Published by the American Physical Society
2024
Holographic
TT¯
deformed entanglement entropy in
dS3/CFT2
Authors: Chen Deyou , Jiang Xin , Yang Haitang
Published: January 2024

In this paper, based on the TT¯ deformed version of dS3/CFT2 correspondence, we calculate the pseudoentropy for an entangling surface consisting of two antipodal points on a sphere and find it is exactly dual to the complex geodesic in the bulk.

Published by the American Physical Society
2024
A new vista on the heterotic moduli space from six and three dimensions
Authors: Del Zotto Michele , Fazzi Marco , Giri Suvendu
Published: January 2024

We settle a longstanding question about the hypermultiplet moduli spaces of the heterotic strings on asymptotically locally Euclidean singularities. These heterotic backgrounds are specified by the singularity type, an instanton number, and a (nontrivial) flat connection at infinity. Building on their interpretation as six-dimensional theories, we determine a class of three-dimensional N=4 quiver gauge theories whose quantum corrected Coulomb branch coincides with the exact heterotic hypermultiplet moduli space.

Published by the American Physical Society
2024