bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Bone Bridge Exposure Using Superficial Temporal Island Flap After Auricle Reconstruction and Bone Bridge Implantation
Authors: Gao Dejin , Ouyang Long , Wang Chenglong , Liu Tun , Chen Qi , Guo Rui , He Bei , Luo Pan , Wang Bingqing , Zhang Qingguo
Published: October 2024

Background:

Congenital microtia usually lead to impairment of both appearance and hearing especially for patients with bilateral microtia. The simultaneous combination of auricular reconstruction and bone bridge implantation has been proved effective and satisfied with the patients. We retrospectively analyzed this method and the complication of it. We summarized and found the application of superficial temporal island flap for repairing the bone bridge exposure.

Methods:

From January 2017 to December 2020, there were 84 patients who underwent the surgery of auricular reconstruction simultaneously combined with bone bridge implantation in the Plastic Surgery Hospital of Chinese Academy of Medical Sciences. And after 12 months follow-up, we evaluated the postoperative effect and collected data on the patients who had bone bridge exposure. We analyzed the reason of the complication and covered the exposed bone bridge with superficial temporal island flap.

Results:

There were 3 cases (3.6%) of implant exposure and the surgical outcome was satisfactory using the repairment of superficial temporal island flap. All 3 patients were healed in 1-stage surgery, and no further implant exposure occurred after another 12-month follow-up.

Conclusions:

The method of auricular reconstruction simultaneously combined with bone bridge implant is an optional choice for patients with bilateral microtia, and has a low incidence of implant exposure. The superficial temporal island flap could well fill the dead space and increase the wear resistance of the tissue, and the scar was not obvious. We found and summarized a satisfactory method of repairing the implantation exposure using the superficial temporal island flap.

Level of Evidence:

Level IV, cases study.
The Impact of Race and Ethnicity in Microvascular Head and Neck Reconstruction Postoperative Outcomes: A Nationwide Data Analysis
Authors: Escobar-Domingo Maria J. , Bustos Valeria P. , Mahmoud Amir-Ala , Kim Erin J. , Miller Amitai S. , Foppiani Jose A. , Alvarez Angelica Hernandez , Lin Samuel J. , Lee Bernard T.
Published: October 2024

Background:

Racial and ethnic disparities have been extensively reported across surgical specialties, highlighting existing healthcare inequities. Nevertheless, evidence is lacking regarding their influence on postoperative outcomes after head and neck reconstruction. This study aimed to evaluate the impact of race and ethnicity on postoperative complications in head and neck microvascular reconstruction.

Methods:

The ACS-NSQIP database was used to identify patients who underwent head and neck microvascular reconstruction between 2012 and 2022. Baseline characteristics were compared based on race (White, non-White) and ethnicity (Hispanic, non-Hispanic). Group differences were assessed using t tests and Fisher Exact tests. Multivariable logistic regression models were constructed to evaluate postoperative complications between the groups. A Cochran-Armitage test was conducted to evaluate the significance of trends over time.

Results:

A total of 11,373 patients met inclusion criteria. Among them, 9,082 participants reported race, and 9,428 reported ethnicity. Multivariable analysis demonstrated that Hispanic patients were more likely to experience 30-day readmission (OR 6.7; 95% CI, 1.17-38.4; P=0.032) and had an average total length of stay of 5.25 days longer (95% CI, 0.84-9.65; P=0.020) compared with non-Hispanic patients. Additional subgroup analyses revealed higher rates of all readmissions among non-White patients, particularly those indicated by malignancy (OR 1.23; 95% CI, 1.1-1.4; P=0.002). No significant differences were found in mortality, reoperation rates, and operative times between racial and ethnic groups.

Conclusions:

The findings of this study suggest that ethnicity may be a significant risk factor for readmission in head and neck microvascular reconstruction. However, future studies are needed to further clarify the impact of race and ethnicity on longer postoperative outcomes, particularly in head and neck cancer minorities.
A Familiar Working Environment Influences Surgeon’s Stress in the Operating Room
Authors: Awtry Jake A. , Skinner Sarah C. , Pascal Léa , Polazzi Stephanie , Lifante Jean-Christophe , Duclos Antoine ,   TopSurgeons Study Group
Published: October 2024

Objective:

To determine the influence of operating room familiarity on surgeon stress.

Background:

Regulating surgeon stress may improve patient safety. This study evaluated how assisting surgeon and operating room familiarity influence intraoperative heart rate variability among surgeons.

Methods:

Attending surgeons from seven specialties within four university hospitals in France were enrolled from 11/01/20-12/31/21. Vagal tone, an indicator of stress derived from heart rate variability, was assessed during the first five minutes after incision using the root mean square of successive differences (RMSSD). Higher RMSSD values indicate greater vagal tone. Team familiarity was quantified as the cumulative time the attending and assisting surgeons had operated together in the past, while operating rooms in which the surgeon conducted >10% of their operations were termed familiar. The effect of each on the RMSSD was assessed via a linear mixed-effect model adjusting for the random effect of the surgeon and possible confounders.

Results:

Overall, 643 surgeries performed by 37 surgeons were included. Median surgeon age was 49 years, 29(78.4%) were male, and 22(59.5%) were professors. Surgeons spent an average of 21.2 hours with the assisting surgeon prior to surgery and conducted 585(91.0%) of their operations in a familiar operating room. For every 10 additional hours spent operating together, ln(RMSSD) significantly increased by 0.018 (95%CI: 0.003 to 0.033, P=0.016). Familiar operating rooms also tended to increase surgeon ln(RMSSD) [0.098 (95%CI: -0.007 to 0.203, P=0.068)].

Conclusion:

Familiar assisting surgeons, and potentially operating rooms, increased surgeon vagal tone. Maintaining a stable operating room environment may improve surgeon stress and patient care.
Formalizing the law of diminishing returns in metabolic networks using an electrical analogy
Authors: Petrizzelli Marianyela , Coton Charlotte , de Vienne Dominique
Published: October 2024

The way biological systems respond to changes in parameter values caused by mutations is a key issue in evolution and quantitative genetics, as it affects fundamental aspects such as adaptation, selective neutrality, robustness, optimality, evolutionary equilibria, etc. We address this question using the enzyme–flux relationship in a metabolic network as a model of the genotype–phenotype relationship. The lack of a suitable mathematical tool from biochemical theory to investigate this relationship led us to use an analogy between electrical circuits and metabolic networks with uni–uni reactions. We show that a behaviour of diminishing returns, which is commonly observed at various phenotypic levels, is inevitable, irrespective of the complexity of the system. We also present a possible generalization to metabolic networks with both uni–uni and bi–bi reactions.
Interactions between reptiles and people: a perspective from wildlife rehabilitation records
Authors: Pyne Teagan , Haering Ron , Sriram Aditi , Lorigan Shona , Shine Richard , Jolly Chris J.
Published: October 2024

As urbanization expands globally, human–wildlife interactions will inevitably increase. Here, we analysed 10 years of wildlife rehabilitation records of squamate (snake and lizard) reptiles (
n
= 37 075) from the Greater Sydney region, New South Wales, Australia, to explore their value to address management and conservation issues. Rescues were highly non-random regarding taxonomic focus, spatial occurrences and temporal trends due to the combined influence of (i) reptile phenology and behaviour and (ii) human perceptions of reptiles. Seasonal peaks in rescues reflect reptile and, to a lesser extent, human activity. Spatial patterns of rescues were informative about distributions and presence of easily identified taxa but were primarily driven by human presence. Larger squamate species were rescued more frequently, potentially reflecting a perception of greater danger or rescue priority. While uncommon species were often misidentified, accurate reports of these taxa may guide targeted surveys. The value of these data for conservation and management could be enhanced by emphasizing reptile identification training of volunteers and use of applications for informed species identification. Wildlife rehabilitation data offer a cost-effective means of quantifying thousands of human–reptile interactions, identifying foci (in both time and space) of human–wildlife conflict such as snakebite risk and roadkill-related reptile mortality.
Pupillary responses to directional uncertainty while intercepting a moving target
Authors: Márquez Inmaculada , Treviño Mario
Published: October 2024

Pupillary responses serve as sensitive indicators of cognitive processes, attentional shifts and decision-making dynamics. Our study investigates how directional uncertainty and target speed (
V
T
) influence pupillary responses in a foveal tracking task involving the interception of a moving dot. Directional uncertainty, reflecting the unpredictability of the target’s direction changes, was manipulated by altering the angular range (AR) from which random directions for the moving dot were extracted. Higher AR values were associated with reduced pupillary diameters, indicating that heightened uncertainty led to smaller pupil sizes. Additionally, an inverse U-shaped relationship between
V
T
and pupillary responses suggested maximal diameters at intermediate speeds. Analysis of saccade-triggered responses showed a negative correlation between pupil diameter and directional uncertainty. Dynamic linear modelling revealed the influence of past successful collisions and other behavioural parameters on pupillary responses, emphasizing the intricate interaction between task variables and cognitive processing. Our results highlight the dynamic interplay between the directional uncertainty of a single moving target,
V
T
and pupillary responses, with implications for understanding attentional mechanisms, decision-making processes and potential applications in emerging technologies.
Re-thinking human interactions with the oceans
Authors: Depledge Michael H.
Published: October 2024

Earth’s marine ecosystems are changing rapidly, in large part owing to the damaging effects of human activities. Unless humans find better ways of interacting with the seas and oceans, the marine resources upon which we rely will diminish as more ecosystems collapse. The consequences for human health and wellbeing will be severe. The meta-discipline of Oceans and Human Health has catalogued how the oceans and their constituents benefit human lives. Examples include access to seafood, pharmaceuticals and physical and mental health benefits. This interdisciplinary research effort has also revealed how the integrated impact of anthropogenic activities has disrupted ocean processes resulting in extensive losses of marine biodiversity, increasing chemical and microbial pollution, proliferation of harmful algal blooms and increased coastal inundation, all of which threaten human populations. In response, non-governmental organizations and national governments have established various agreements and treaties to prevent further damage, restore what has been lost and grasp new economic opportunities. Nevertheless, ocean-related risks continue to escalate rapidly in the absence of political commitment. New thinking regarding the interconnectedness of all human/ocean interactions is required to remove the barriers and impediments that hamper tackling the wicked problem of fostering health and wellbeing while achieving ocean sustainability.
FlightTrackAI: a robust convolutional neural network-based tool for tracking the flight behaviour of
Aedes aegypti
mosquitoes
Authors: Javed Nouman , López-Denman Adam J. , Paradkar Prasad N. , Bhatti Asim
Published: October 2024

Monitoring the flight behaviour of mosquitoes is crucial for assessing their fitness levels and understanding their potential role in disease transmission. Existing methods for tracking mosquito flight behaviour are challenging to implement in laboratory environments, and they also struggle with identity tracking, particularly during occlusions. Here, we introduce FlightTrackAI, a robust convolutional neural network (CNN)-based tool for automatic mosquito flight tracking. FlightTrackAI employs CNN, a multi-object tracking algorithm, and interpolation to track flight behaviour. It automatically processes each video in the input folder without supervision and generates tracked videos with mosquito positions across the frames and trajectory graphs before and after interpolation. FlightTrackAI does not require a sophisticated setup to capture videos; it can perform excellently with videos recorded using standard laboratory cages. FlightTrackAI also offers filtering capabilities to eliminate short-lived objects such as reflections. Validation of FlightTrackAI demonstrated its excellent performance with an average accuracy of 99.9%. The percentage of correctly assigned identities after occlusions exceeded 91%. The data produced by FlightTrackAI can facilitate analysis of various flight-related behaviours, including flight distance and volume coverage during flights. This advancement can help to enhance our understanding of mosquito ecology and behaviour, thereby informing targeted strategies for vector control.
Nonlinear parametric models of viscoelastic fluid flows
Authors: Oishi C. M. , Kaptanoglu A. A. , Kutz J. Nathan , Brunton S. L.
Published: October 2024

Reduced-order models (ROMs) have been widely adopted in fluid mechanics, particularly in the context of Newtonian fluid flows. These models offer the ability to predict complex dynamics, such as instabilities and oscillations, at a considerably reduced computational cost. In contrast, the reduced-order modelling of non-Newtonian viscoelastic fluid flows remains relatively unexplored. This work leverages the
sparse identification of nonlinear dynamics
(SINDy) algorithm to develop interpretable ROMs for viscoelastic flows. In particular, we explore a benchmark oscillatory viscoelastic flow on the four-roll mill geometry using the classical Oldroyd-B fluid. This flow exemplifies many canonical challenges associated with non-Newtonian flows, including transitions, asymmetries, instabilities, and bifurcations arising from the interplay of viscous and elastic forces, all of which require expensive computations in order to resolve the fast timescales and long transients characteristic of such flows. First, we demonstrate the effectiveness of our data-driven surrogate model to predict the transient evolution and accurately reconstruct the spatial flow field for fixed flow parameters. We then develop a fully parametric, nonlinear model capable of capturing the dynamic variations as a function of the Weissenberg number. While the training data are predominantly concentrated on a limit cycle regime for moderate

W
i

, we show that the parametrized model can be used to extrapolate, accurately predicting the dominant dynamics in the case of high Weissenberg numbers. The proposed methodology represents an initial step in applying machine learning and reduced-order modelling techniques to viscoelastic flows.
Self-folding of two-dimensional thin templates into pyramidal microstructures by a liquid drop: a numerical model
Authors: Lecrivain Gregory , Lorenz Pierre , Zimmer Klaus , Hampel Uwe
Published: October 2024

We present a numerical framework bringing together a structural and a surface-energy minimization model to compute nano- and microorigami self-folding processes, that are three-dimensional in nature. A liquid drop, initially at rest on the template, triggers the spontaneous folding and deforms dynamically with the template. As application, the self-folding of thin two-dimensional templates into pyramidal microstructures is simulated. Each template is composed of a fixed regular base connected to rigid triangular side panels by two elastic hinges. We presently determine the condition, at which the transition from partial to full drop encapsulation occurs. The present model makes use of phase fields to numerically represent the drop and the template. This allows to: (i) develop an efficient computational method, which incorporates time-derivative terms and (ii) study three-dimensional complex self-folding processes.
Body size decline during thermal evolution is only detected at mild temperature
Authors: Antunes Marta A. , Grandela Afonso , Santos Marta A. , Santos Mauro , Matos Margarida , Simões Pedro
Published: October 2024

Body size is a key morphological trait that affects physiology and metabolism, as well as other relevant traits such as fertility and mating success. Some evidence points to a trend of shrinking body size with increasing temperature, but this is far from unequivocal. Here, we assess the evolution of body size under a warming environment in experimentally evolved
Drosophila subobscura
populations from two distinct geographical origins, tested in both ancestral and warming environments. We observed a decrease in body size in the warming populations, but only in the lower-latitude populations and only when tested in the ancestral (control) environment. The absence of a body size response in the warming environment may be owing to a balance between forces promoting thermodynamic stability—leading to a tendency for body size to decrease—and selection for increased reproductive output—leading to an increase in body size. Our findings indicate that body size variation is complex, with genotype-by-environment interactions occurring. This may explain the lack of consistency across studies. This highlights that predictions of body size evolution under climate warming are not straightforward and emphasizes the need for considering intra- and inter-specific variation in future studies.
Overcoming the pitfalls of categorizing continuous variables in ecology, evolution and behaviour
Authors: Beltran Roxanne S. , Tarwater Corey E.
Published: October 2024

Many variables in biological research—from body size to life-history timing to environmental characteristics—are measured continuously (e.g. body mass in kilograms) but analysed as categories (e.g. large versus small), which can lower statistical power and change interpretation. We conducted a mini-review of 72 recent publications in six popular ecology, evolution and behaviour journals to quantify the prevalence of categorization. We then summarized commonly categorized metrics and simulated a dataset to demonstrate the drawbacks of categorization using common variables and realistic examples. We show that categorizing continuous variables is common (31% of publications reviewed). We also underscore that predictor variables can and should be collected and analysed continuously. Finally, we provide recommendations on how to keep variables continuous throughout the entire scientific process. Together, these pieces comprise an actionable guide to increasing statistical power and facilitating large synthesis studies by simply leaving continuous variables alone. Overcoming the pitfalls of categorizing continuous variables will allow ecologists, ethologists and evolutionary biologists to continue making trustworthy conclusions about natural processes, along with predictions about their responses to climate change and other environmental contexts.
Global primary predictors of extinction risk in primates
Authors: Galán-Acedo Carmen , Verde Arregoitia Luis Darcy , Arasa-Gisbert Ricard , Auliz-Ortiz Daniel , Saldivar-Burrola Laura L. , Gouveia Sidney F. , Correia Isadora , Rosete-Vergés Fernando Antonio , Dinnage Russell , Villalobos Fabricio
Published: October 2024

Identifying the main predictors of species’ extinction risk while accounting for the effects of spatial and phylogenetic structures in the data is key to preventing species loss in tropical forests through adequate conservation practices. We recorded 22 705 precise geographical locations of primate occurrence across four major geographic realms (Neotropics, mainland Africa, Madagascar and Asia) to assess predictors of threat status using a novel Bayesian spatio-phylogenetic approach. We estimated the relative contributions of fixed factors (forest amount, body mass, home range, diel activity, locomotion, evolutionary distinctiveness and climatic instability) and random factors (space and phylogeny) to primate extinction risk. Precipitation instability increased the extinction risk in the Neotropics but decreased it in mainland Africa and Madagascar. Forest amount was negatively associated with extinction risk in all realms except Madagascar. Body mass increased the extinction risk in the Neotropics and Madagascar, whereas home range increased the extinction risk in mainland Africa and decreased it in Asia. Evolutionary distinctiveness negatively influenced extinction risk only in mainland Africa. Our findings highlight the importance of climate change mitigation and forest protection strategies. Increasing the protection of large primates and reducing hunting are also essential.
Bacterial skin infection caused by a plant pathogen Kosakonia cowanii - Identification with the MALDI Biotyper Sirius one and susceptibility testing
Authors: Merlino John , Pillay Kiora , Rizzo Sophia , Baskar Sai Rupa , Seed Daniel , Siarakas Steven , Hettiarachchi Ravin , McKew Genevieve , Gray Timothy
Published: October 2024

Kosakonia cowanii is a Gram-negative bacillus belonging to the order Enterobacterales. Kosakonia cowanii is a plant pathogen, we report the isolation of this organism from a gardening puncture injury from a plant. Pus examined from the site of infection showed the infecting organism as Kosakonia cowanii by MALDI-TOF MS Biotyper Sirius one and 16s rRNA analysis. The organism failed to be identified biochemically by the Vitek 2 XL identification system as Kosakonia spp.. The Gram-negative bacilli on the system was biochemically identified as Pantoea spp.. Difficulties in species identification biochemically suggests that potentially, Kosakonia cowanii might represent an underestimated opportunistic human pathogen in skin infections associated with plant injuries. The MALDI-TOF MS Biotyper Sirius one software was found to be a fast and reliable identification of the organism. The isolate was found to be susceptible to first generation cephalosporins, both to cefalexin and cefazolin by disc diffusion and Vitek 2 XL even though antibiotic breakpoints currently do not exist using EUCAST or CLSI guidelines for this organism.
Emendation of Appendix 9 of the International Code of Nomenclature of Prokaryotes to regulate the use of connecting vowels in compound names after stems ending in the same vowel
Authors: Oren Aharon
Published: October 2024

Following a proposal to emend Appendix 9 of the International Code of Nomenclature of Prokaryotes with guidelines to regulate the use of connecting vowels in compound names after stems ending in the same vowel, I here report the outcome of the ballot on this proposal by the members of the International Committee on Systematics of Prokaryotes. The new guidelines to be incorporated in Appendix 9 are presented.
Ultra-processed food consumption and risk of lung cancer: Results from a Prospective Study
Authors: Mekonnen Tefera Chane , Melaka Yohannes Adama , Shi Zumin , Gill Tiffany K
Published: October 2024

Background and Aims

There is limited evidence on the link between ultra-processed food (UPF) intake and the risk of lung cancer (LC). This study examined the association between UPF and LC risk using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer trial.

Methods

This study involved PLCO participants (n = 96,607, aged ≥ 55 years) who were followed between 1998 and 2009. Food items were categorized based on the NOVA classification. Cox regression models with inverse probability of censoring weighting (IPCW) were utilized to estimate the association between UPF intake and LC risk. The joint effect of UPF and diabetes was explored using additive hazard models to calculate the additional number of LC cases.

Results

During a median follow-up period of 9.4 years, 1,596 incident LC cases were identified. UPF consumption (in %gram/day) showed no significant association with the overall risk of LC. However, adults with diabetes in the highest quintile of UPF intake had a significantly higher risk of LC (HR = 2.44; 95% CI: 1.27, 4.67) compared to participants without diabetes. A small excess risk due to the interaction between UPF and diabetes (0.13; 95% CI −0.32, 0.58) was observed, resulting in an additional 201 cases of LC per 105person-years (95% CI: 70, 332) attributed to the highest UPF intake and diabetes interaction. Furthermore, a 10% increment in UPF intake (%kcal/day) increased the risk of LC by 32%.

Conclusions

While UPF, in terms of weight contribution, is associated with a higher risk of LC in participants with diabetes, UPF (in %kcal/day), is associated with an increased risk of LC in all participants. Lowering UPF intake may help reduce the risk of LC in both diabetic patients and the general population.
Deciphering the role of the nanoscale clustering of activating and costimulatory antibodies on T cell activation
Authors: Le Saux Guillaume , Nowakowski Piotr , Toledo Esti , Tzdaka Sivan , Al-Kader Yassin Abed , Naaz Shagufta , Segal Yuval , Maman Brit , Porgador Angel , Smith Ana-Sunčana , Schvartzman Mark
Published: October 2024

In a joint experimental and a modeling effort, we explored the regulation of T cell activation and cytotoxicity by the nanoscale clustering and surface density of activating and costimulatory antibodies. Specifically, we simulated T cells on nanolithographically patterned arrays of clusters of these antibodies, systematically varying the cluster size from intermediate to large and overall antibody density. We found that T-cell activation correlated more with global antibody density than with cluster size, such that at low density arrays were inefficient in activation, while high density arrays saturated the signal. However, when T-cells were exposed to patterns of low global densities but small, very dense clusters, full activation of T cells was achieved. These results could be rationalized using the membrane-fluctuation-model that integrates the cooperative effects between bonds with mechanical feedback from the cell activation. This insight into the spatial organization of activating ligands provides an important understanding of the mechanism of T cell activation and allows for the design of more effective T cell activation platforms for immunotherapy.
Evaluation of scalp-based targeting methods of dorsolateral prefrontal cortex for transcranial magnetic stimulation therapy: Electroencephalogram cap, Beam F3, CPC F3, and adjusted Beam F3
Authors: Jiang Yihan , Chen Yuanyuan , Wei Lijiang , Liu Farui , Zheng Zeqing , Zhang Zong , Li Zheng , Tang Yingying , Wang Jijun , Xie Qing , Niu Chuanxin M. , Zhu Chaozhe
Published: October 2024

Background

Repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex (DLPFC) offers a promising approach for treating depression. Scalp-based targeting methods, including EEG Cap, Beam F3, CPC F3, and adjusted Beam F3, have evolved to improve clinical application.

Obejectives

To evaluate and compare the accuracy, reliability, speed, and training efficacy of these four methods.

Methods

Three trained technicians conducted repeated DLPFC targeting measurements on 10 3D-printed head models. Accuracy was assessed by calculating targeting error and electric field strength at the subgenual anterior cingulate cortex anti-correlated peak. Reliability was evaluated through inter- and intra-rater variability, and training efficacy was examined by comparing targeting errors between trained technicians and novices.

Results

CPC F3, Beam F3, and adjusted Beam F3 demonstrated comparable accuracy in terms of electric field strength, but CPC F3 had the lowest targeting error (4.2 mm). CPC F3 also exhibited the highest reliability (inter-rater variability at 3.3 mm, intra-rater variability at 2.3 mm). The EEG cap was the fastest method (80 seconds), while CPC F3 was faster than Beam F3 but slower than EEG Cap. No significant differences in targeting error between trained technicians and novices were noted with CPC F3 and adjusted Beam F3.

Conclusion

The comparative analysis of four scalp-based targeting methods provides insights that can enhance clinical decision-making and the practical application. While accuracy among CPC F3, Beam F3, and adjusted Beam F3 was comparable, CPC F3 emerges as highly practical due to its significantly better reliability, training efficacy, moderate speed, and straightforward implementation.
A newly identified pathology of Episodic Angioedema with Hypereosinophilia (Gleich’s Syndrome) revealed by Multi-Omics Analysis
Authors: Koreeda Tatsuya , Muraoka Hirokazu , Sato Yasunori
Published: October 2024

Episodic Angioedema with Eosinophilia (Gleich syndrome) is a rare disease characterized by periodic angioedema, fever, and marked eosinophilia. This study aimed to elucidate the pathogenic factors of severe Gleich syndrome through comprehensive multi-omics analysis, including whole genome sequencing (WGS) and RNA sequencing (RNA-seq). A young female patient (age: 16-20 years old) presenting with periodic high fever, extensive urticaria/eczema, and marked eosinophilia was diagnosed with Gleich syndrome. The symptoms were severe, showing no spontaneous remission, but responded to oral steroid therapy with mild resolution. WGS of the patient’s blood identified high-impact pathogenic mutations in 16 genes, including PRDM16. RNA-seq analysis revealed differentially expressed genes (DEGs) associated with immune response regulation and viral defense. Combined z-score analysis of WGS and RNA-seq data highlighted ACE as a key gene, with its expression significantly downregulated during disease progression and recovered with treatment. IFNG was also identified. The findings suggest that decreased ACE expression, driven by PRDM16 mutations and altered IFNG expression, likely contributed to increased bradykinin levels and activation of the arachidonic acid cascade, resulting in the severe inflammation and angioedema characteristic of Gleich syndrome. This study highlights the utility of integrating WGS and RNA-seq data to uncover the molecular basis of rare diseases and provides a foundation for developing therapeutic strategies for hypereosinophilic syndromes.
Reversible and Noninvasive Modulation of a Historical Surgical Target for Depression with Low Intensity Focused Ultrasound
Authors: Tsuchiyagaito Aki , Kuplicki Rayus , Misaki Masaya , Edwards Landon S. , Camprodon Joan A. , Fitzgerald Kate D. , Khalsa Sahib S. , Philip Noah S. , Paulus Martin P. , Guinjoan Salvador M.
Published: October 2024

Major depressive disorder has a point prevalence of 5% of the world population and is the main cause of disability, with up to a third of patients not responding to first-line treatments. Surgical neuromodulation is offered to only an anecdotal proportion of these patients, because while these methods are curative in some individuals, the proportion of responders rarely exceeds 50%. Recent efforts to establish reliable brain circuit-symptom relationships and thus predict response have involved mapping with multiple intracranial electrodes, but the impracticality of this approach currently prevents its application at scale. In the present study (ClinicalTrials.govidentifierNCT05697172; FDA Q220192) we begin to address this gap by leveraging low-intensity focused ultrasound (LIFU), a novel noninvasive technique, to modulate the anterior limb of the internal capsule, which is an established surgical deep white matter target for depression. We based our study on burgeoning in vitro evidence that LIFU attenuates axonal conduction by operating mechanosensitive channels in nodes of Ranvier. Compared with sham stimulus, active LIFU produced a functional disconnection of gray matter hubs reached by the sonicated axonal tracts, an increase in positive emotion, and top-down effects on the cardiovascular autonomic balance. Our results using LIFU of deep-brain white matter tracts in humans open three potential avenues to understand the mechanisms and improve the outcome of depression, namely attaining a personalized definition of brain circuit-symptom relationships, serving as a noninvasive probe for neuromodulation before irreversible procedures in a “try before you buy” approach, and ultimately emerging as a therapeutic intervention itself.
Spring-loaded DNA origami arrays as energy-supplied hardware for modular nanorobots
Authors: Pfeiffer Martina , Cole Fiona , Wang Dongfang , Ke Yonggang , Tinnefeld Philip
Published: October 2024

DNA origami nanodevices allow us to mimic cellular functions in a rationally controlled manner. They describe machineries which respond to environmental stimuli by conducting different tasks. To date, this mostly is achieved by constructing conformational two-state switches which upon activation by stimuli change their conformation resulting in the performance of a priorly programmed task. Their applicability however is often limited to a single, specific stimuli – output combination due to their intrinsic properties as two-state systems only. This makes expanding them further to include multiple stimuli/ outputs challenging. Here, we address this problem by introducing reconfigurable DNA origami arrays as a coupled network of two-state systems. We use this network to create a universal design strategy in which different operational units can be incorporated into any two-state system of our nanorobot. The resulting nanorobot is capable of receiving different stimuli, computing the response to the received stimuli using multi-level Boolean logic gating and yielding multiple programmed output operations with controlled order, timing and spatial position. We expect that this strategy will be a crucial step towards further developing DNA origami nanorobots for applications in various technological fields.
The Deubiquitinating Enzyme Otub2 Modulates Pancreatic Beta-Cells Function and Survival
Authors: Oshry Michal , Isaac Roi , Boura-Halfon Sigalit , Sampson Sanford , Lev Sima , Zick Yehiel , Vinik Yaron
Published: October 2024

We have previously shown that otubain 2 (OTUB2), a deubiquitinating enzyme, inhibits caspase-3/7 activity in primary human islets; promotes insulin secretion and inhibits cytokine-induced nuclear factor-κB (NFκB) activity. In the present work we show that overexpression of Otub2 in MIN6 cells inhibits NFκB activity and the expression of its target genes MCP-1 and iNOS. Consequently, both the basal and the cytokine-induced apoptosis of cultured MIN6 cells and dispersed human islets were inhibited. Overexpression of Otub2 in MIN6 cells increase the mRNA levels of NKx6.1 and Glut2 and concomitantly increased glucose-stimulated insulin secretion (GSIS) (by 2-3-fold). The beneficial effects of Otub2 on β-cell function was demonstrated by the phenotype ofOtub2-/+andOtub2-/-mice, which manifested impaired glucose tolerance and increased expression of NFkB target genes (e.g. IP-10, MCP-1 and IL-1β). RNAseq analysis of pancreata derived from OTUB2 KO mice revealed reduced expression of genes that down regulate K+transporters (e.g.Ank2,Cacna1aandKcnab1)combined with an increase in oxidative phosphorylation related genes. Given that closure of K+channels is crucial for insulin secretion, these results could account, at least in part, for the impaired GSIS in the OTUB2 KO mice. Indeed, mass-spectrometry analysis of proteins co-immunoprecipitated with Otub2 revealed the voltage-gated potassium channel subunit Kv9.3 as a major Otub2 binding-partner. Additional binding partners included the Peg3 and Camk2d proteins, which promote NFκB signaling and β-cell death. Hence, by deubiquitinating proteins in complexes that contain Peg3 and Camk2d, Otub2 might inhibit propagation of NFκB signaling and β-cell apoptosis. Collectively our findings implicate Otub2 as a key regulator of β cell function, mainly affecting NFkB signaling and the K+channels that regulate insulin secretion.
An accelerated molecular dynamics study for investigating protein pathways using the bond-boost hyperdynamics method
Authors: Park Soon Woo , Choi Moon-ki , Lee Byung Ho , Seo Sangjae , Kim Woo Kyun , Kim Moon Ki
Published: October 2024

Molecular dynamics (MD) simulation is an important tool for understanding protein dynamics and the thermodynamic properties of proteins. However, due to the high computational cost of MD simulations, it is still challenging to explore a wide conformational space. To solve this problem, a variety of accelerated MD schemes have been proposed over the past few decades. The bond-boost method (BBM) is one of such accelerated MD schemes, which expedites escape events from energy basins by adding a bias potential based on changes in bond length. In this paper, we present a new methodology based on the BBM for accelerating the conformational transition of proteins. In our modified BBM, the bias potential is constructed using the dihedral angle and hydrogen bond, which are more suitable variables to monitor the conformational change in proteins. Additionally, we have developed an efficient algorithm compatible with the LAMMPS package. The method is validated with the conformational change of Adenylate kinase (AdK) by comparing the conventional and accelerated MD simulation results. Based on the accelerated MD results, the characteristics of AdK are investigated by monitoring the conformational transition pathways and the behavior of interdomain salt bridges. Moreover, the free energy landscape calculated using umbrella sampling confirms all the states identified by the accelerated MD simulation are the free energy minima and the system makes transitions following the path indicated by the free energy landscape. Our efficient approach is expected to play a key role in investigating transition pathways in a wide range of protein simulations.
Capturing Optimal and Suboptimal behavior Of Agents Via Structure Learning Of Their Internal Model
Authors: James Ashwin , Bethus Ingrid , Muzy Alexandre
Published: October 2024

This study introduces a novel framework for understanding the cognitive underpinnings of individual behavior which often deviates from rational decision-making aimed at maximizing rewards in real-life scenarios. We propose a structure learning approach to infer an agent’s internal model, composed of a learning rule and an internal representation of the environment. Crucially, the combined contribution of these components — rather than their individual contribution — determines the overall optimality of the agent’s behavior. By exploring various combinations of learning rules and environment representations, we identify the most probable agent model structure for each individual. We apply this framework to analyze rats’ learning behavior in a free-choice task within a T-maze with return arms, evaluating different internal models based on optimal and suboptimal learning rules, along with multiple possible representations of the T-maze decision graph. Identifying the most likely agent model structure based on the rats’ behavioral data reveals that slower learning rats employed either a suboptimal or a moderately optimal agent model, whereas fast learners employ an optimal agent model. Using the inferred agent models for each rat, we explore the qualitative differences in their individual learning processes. Policy entropy, derived from the inferred agent models, also highlights variations in the balance between exploration and exploitation strategies among the rats. Traditional reinforcement learning approaches to addressing suboptimal behavior focus separately on either suboptimal learning rules or flawed environment representations. Our approach jointly models these components, revealing that suboptimal decisions can arise from complex interactions between learning rules and environment representations within an agent’s internal model. This provides deeper insights into the cognitive mechanisms underlying real-world decision-making.
Multiple transcription factors regulate the expression of genes for error prone DNA polymerases in Acinetobacter baumannii
Authors: Nguyen Brian H , Ching Carly , Macguire Ashley , Casula Pranav , Newman Connor , Finley Faith , Godoy Veronica
Published: October 2024

Acinetobacter baumannii is an opportunistic pathogen causing several infections that are increasingly difficult to treat due to its ability to rapidly gain antibiotic resistances. These resistances can arise due to mutations during the DNA damage response (DDR), through the activity of error-prone DNA polymerases, such as DNA polymerase V (DNA Pol V). Currently, the DDR in A. baumannii is not well understood and the regulation of genes encoding multiple copies of DNA Pol V is not fully characterized. Through genome wide mutagenesis, we have identified a novel TetR-like family regulator of genes that encode DNA Pol V, which we have named Error-prone polymerase regulator, EppR. We have found that EppR represses the expression of the genes encoding DNA Pol V and itself through direct binding to a conserved EppR motif in their promoters. Lastly, we show that EppR also regulates UmuDAb, previously identified as a regulator of genes encoding DNA Pol V. These two gene products are functionally required to ensure regulation of expression of genes encoding DNA Pol Vs and umuDAb. With these results, we propose a co-repressor model for the regulation of genes encoding DNA Pol V and umuDAb.
Enhanced scattering from an almost-periodic optical temporal slab
Authors: Koufidis Stefanos Fr. , Koutserimpas Theodoros T. , Monticone Francesco , McCall Martin W.
Published: October 2024

We showcase the impact of almost-periodicity on the parametric amplification associated with the first-order momentum gap in photonic time-crystals with time-varying permittivity. Utilizing a vectorial coupled-wave theory approach, we rigorously analyze the scattering by a temporal slab of the considered medium. We pinpoint a critical regime wherein flaws in material tuning paradoxically enhance amplification due to the coupling of fewer, broader modes, resulting in a higher and broader pulselike amplification envelope. Additionally, we demonstrate that the intensity reflectances of time-reversed waves corresponding to secondary “Bragg” resonances achieve remarkably high levels of subharmonic parametric amplification, with the epsilon-near-zero regime serving as a preferred candidate for experimental implementation. Our counterintuitive findings highlight the potential of intentionally leveraging modulation desynchronization and impurities in the temporal unit cell of photonic time-crystals to enhance both the level and the bandwidth of amplification.

Published by the American Physical Society
2024
Complementarity for a dynamical black hole
Authors: Concepcion Benjamin , Nomura Yasunori , Ritchie Kyle , Weiss Samuel
Published: October 2024

Black hole complementarity posits that the interior of a black hole is not independent from its Hawking radiation. This leads to an apparent violation of causality: the interior can be acausally affected by operators acting solely on the radiation. We argue that this perspective is misleading and that the black hole interior must be viewed as existing in the causal past of the Hawking radiation, despite the fact that they are spacelike separated in the semiclassical description. Consequently, no operation on the Hawking radiation—no matter how complex—can affect the experience of an infalling observer. The black hole interior and the radiation only appear spacelike separated in the semiclassical description because an infalling observer’s ability to access complex information is limited; the chaotic dynamics on the horizon, as viewed from the exterior, then converts any effect caused by such an observer to information in the Hawking radiation which cannot be accessed at the semiclassical level. We arrive at the picture described above by considering a unitary exterior description in which the flow of information is strictly causal, which we extend to apply throughout the entire history of black hole evolution, including its formation. This description uses the stretched event horizon as an inner edge of spacetime, on which the information inside is holographically encoded. We argue that the global spacetime picture arises from coarse graining over black hole microstates, and discuss its relationship with the exterior description.

Published by the American Physical Society
2024
Pole-skipping and chaos in D3-D7 brane systems
Authors: Baishya Banashree , Chakrabarti Sayan , Maity Debaprasad , Nayek Kuntal
Published: October 2024

In this paper, we analyze the pole-skipping phenomena of finite temperature Yang-Mills theory with quark flavors, which is dual to D3-D7 brane systems in bulk. We also consider the external electric field in the boundary field theory, which is dual to the world volume electric field on the D7 brane. We will work in the probe limit where the D7 branes do not backreact to the D3 brane background. In this scenario, we decode the characteristic parameters of the chaos, namely, Lyapunov exponent λL and butterfly velocity vb from the pole-skipping points by performing the near effective horizon analysis of the linearized Einstein equations. Unlike pure Yang-Mills, once charged quarks with a background electric field are added into the system, the characteristic parameters of the chaos show nontrivial dependence on the quark mass and external electric field. We have observed that λL and vb decreases with increasing electric field. We further perform the pole-skipping analysis for the gauge invariant sound, shear, and tensor modes of the perturbation in the bulk and discuss their physical importance in the holographic context.

Published by the American Physical Society
2024
Characterization of sub-micrometre-sized voids in fixed human brain tissue using scanning X-ray microdiffraction
Authors: Nepal Prakash , Bashit Abdullah A. , Makowski Lee
Published: October 2024

Using a 5 µm-diameter X-ray beam, we collected scanning X-ray microdiffraction in both the small-angle (SAXS) and the wide-angle (WAXS) regimes from thin sections of fixed human brain tissue from Alzheimer's subjects. The intensity of scattering in the SAXS regime of these patterns exhibits essentially no correlation with the observed intensity in the WAXS regime, indicating that the structures responsible for these two portions of the diffraction patterns, which reflect different length scales, are distinct. SAXS scattering exhibits a power-law behavior in which the log of intensity decreases linearly with the log of the scattering angle. The slope of the log–log curve is roughly proportional to the intensity in the SAXS regime and, surprisingly, inversely proportional to the intensity in the WAXS regime. We interpret these observations as being due to the presence of sub-micrometre-sized voids formed during dehydration of the fixed tissue. The SAXS intensity is due largely to scattering from these voids, while the WAXS intensity derives from the secondary structures of macromolecular material surrounding the voids. The ability to detect and map the presence of voids within thin sections of fixed tissue has the potential to provide novel information on the degradation of human brain tissue in neurodegenerative diseases.