bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated visual acuity estimation by optokinetic nystagmus using a stepped sweep stimulus
Authors: Turuwhenua Jason , LinTun Zaw , Norouzifard Mohammad , Edmonds Misty , Findlay Rebecca , Black Joanna , Thompson Benjamin
Published: September 2024

Purpose

To describe an automatic system for objective measurement of visual acuity (VA) using optokinetic nystagmus (OKN). This pilot study tested the system's sensitivity and specificity for detecting reduced VA in healthy adults by comparing VA‐OKN to VA with an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart (VA‐ETDRS).

Methods

Adult participants (age 30 ± 12 years) with either reduced VA (n = 11, VA‐ETDRS > 0.20 logMAR) or normal VA (n = 12, VA‐ETDRS ≤ 0.20 logMAR) completed monocular VA‐OKN measurements in each eye. The VA‐OKN stimulus was an array of drifting (5°/s) vanishing discs presented in descending/ascending size order (0.00–1.00 logMAR in 0.10 steps). The stimulus was stepped every 2 s, and 10 sweeps were shown per eye (five ascending and five descending). Eye‐tracking data determined when OKN activity ceased (descending sweep) or began (ascending sweep), which was used to determine VA‐OKN for each sweep. The estimates were averaged across sweeps to produce an automated VA‐OKN. The automated sweeps were then provided in randomised order to a reviewer blinded to the VA‐ETDRS findings who determined a final VA‐OKN for an eye.

Results

A single randomly selected eye from each observer was used for analysis. The sensitivity and specificity of VA‐OKN using the same 0.20 logMAR threshold as VA‐ETDRS was 100%. Comparisons between the VA‐OKN and VA‐ETDRS measures were made for participants in the reduced VA group. There was no significant difference between VA‐OKN and VA‐ETDRS (p = 0.55) and the two measures produced comparable values (r2 = 0.84, 95% limits of agreement = 0.19 logMAR, intra‐class correlation coefficient = 0.90 [95% CI:0.68–0.97]).

Conclusions

Visual acuity using optokinetic nystagmus correctly identified a VA deficit in adults and for those with a VA deficit, VA‐OKN was strongly correlated with the gold‐standard clinical measure of VA. OKN is a promising method which has the potential for use in cognitively impaired adults and pre‐verbal children.
Deciphering the Role of SVP‐Like Genes and Their Key Regulation Networks During Reproductive Cone Development in Pinus tabuliformis
Authors: Zhou Chengcheng , Liu Hongmei , Wang Huili , Niu Shihui , El‐Kassaby Yousry A. , Li Wei
Published: September 2024

Reproductive development plays an essential role in the perpetuation of genetic material and environmental adaptation. In angiosperms, the Short Vegetative Phase (SVP) serves as a flowering repressor, influencing the development of floral organs. In this study, heterologous transformation of Arabidopsis thaliana with SVP‐like genes (PtSVL1 and PtSVL2) derived from Pinus tabuliformis significantly impacted stamen formation and pollen fertility, without altering flowering time. Gene co‐expression networks revealed that SVP‐like and SOC1‐like genes function as key coregulatory transcription factors during the initial stages of cone development in P. tabuliformis. Interestingly, the regulatory module of SOC1 regulated by SVP in angiosperms is absent in conifers and conifer SVP‐like exercises its function in a form that is physically bound to SOC1‐like. Furthermore, combining the yeast one‐hybrid scanning with co‐expression network analysis, revealed that SPLs and TPSs were the principal downstream target genes of PtSVL1. Notably, the PtSPL16 promoter is positively regulated by PtSVL1, and overexpression of PtSPL16 results in delayed flowering in Arabidopsis, suggesting that the PtSVL1‐PtSPL16 module plays a crucial role in regulating reproductive development in conifers. Collectively, these findings enhance our understanding of the roles of SVP‐like genes in conifers and the key regulatory networks centred on PtSVL1 during reproductive cone development.
Clinical significance of direct fast scarlet staining on the diagnosis of eosinophilic colitis: A comparative study focusing on the eosinophil degranulation in colonic mucosal tissue
Authors: Ikeda Mina , Kato Hiroyuki , Arakawa Satoshi , Kobayashi Takashi , Hashimoto Senju , Katano Yoshiaki , Inada Ken‐ichi , Kiriyama Yuka , Ishihara Takuma , Yamamoto Satoshi , Asano Yukio , Horiguchi Akihiko
Published: September 2024

This study aimed to validate the DFS (direct fast scarlet) staining in the diagnosis of EC (eosinophilic colitis). The study included 50 patients with EC and 60 with control colons. Among the 60 control samples, 39 and 21 were collected from the ascending and descending colons, respectively. We compared the median number of eosinophils and frequency of eosinophil degranulation by HE (hematoxylin and eosin) and DFS staining between the EC and control groups. In the right hemi‐colon, eosinophil count by HE was useful in distinguishing between EC and control (41.5 vs. 26.0 cells/HPF, p < 0.001), but the ideal cutoff value is 27.5 cells/HPF (high‐power field). However, this method is not useful in the left hemi‐colon (12.5 vs. 13.0 cells/HPF, p = 0.990). The presence of degranulation by DFS allows us to distinguish between the groups even in the left hemi‐colon (58% vs. 5%, p < 0.001). DFS staining also enabled a more accurate determination of degranulation than HE. According to the current standard to diagnose EC (count by HE staining ≥20 cells/HPF), mucosal sampling from left hemi‐colon is problematic since the number of eosinophils could not be increased even in EC. Determination of degranulated eosinophils by DFS may potentiate the diagnostic performance even in such conditions.
Synergistic effects of melatonin and glycine betaine on seed germination, seedling growth, and biochemical attributes of maize under salinity stress
Authors: Su Wennan , Qiu Jiaoqi , Soufan Walid , El Sabagh Ayman
Published: September 2024

Salinity stress represents a major threat to crop production by inhibiting seed germination, growth of seedlings, and final yield and, therefore, to the social and economic prosperity of developing countries. Recently, plant growth‐promoting substances have been widely used as a chemical strategy for improving plant resilience towards abiotic stresses. This study aimed to determine whether melatonin (MT) and glycine betaine (GB) alone or in combination could alleviate the salinity‐induced impacts on seed germination and growth of maize seedlings. Increasing NaCl concentration from 100 to 200 mM declined seed germination rate (4.6–37.7%), germination potential (24.5–46.7%), radical length (7.7–40.0%), plumule length (2.2–35.6%), seedling fresh (1.7–41.3%) and dry weight (23.0–56.1%) compared to control (CN) plants. However, MT and GB treatments lessened the adverse effects of 100 and 150 mM NaCl and enhanced germination comparable to control plants. In addition, results from the pot experiments show that 200 mM NaCl stress disrupted the osmotic balance and persuaded oxidative stress, presented by higher electrolyte leakage, hydrogen peroxide, superoxide radicals, and malondialdehyde compared to control plants. However, compared to the NaCl treatment, NaCl+MT+GB treatment decreased the accumulation of malondialdehyde (24.2–42.1%), hydrogen peroxide (36.2–44.0%), and superoxide radicals (20.1–50.9%) by up‐regulating the activity of superoxide dismutase (28.4–51.2%), catalase (82.2–111.5%), ascorbate peroxidase (40.3–59.2%), and peroxidase (62.2–117.9%), and by enhancing osmolytes accumulation, thereby reducing NaCl‐induced oxidative damages. Based on these findings, the application of MT+GB is an efficient chemical strategy for improving seed germination and growth of seedlings by improving the physiological and biochemical attributes of maize under 200 mM NaCl stress.
Introduction and overview on Autogenous Platelet Concentrates
Authors: Quirynen Marc , Sculean Anton , Blanco Juan , Wang Hom‐Lay , Donos Nikos
Published: September 2024

This special issue on autologous platelet concentrates (APCs) provides clinicians with an overview on the current understanding of the use of these biomaterials for soft and hard tissue regeneration. The included papers summarize scientific evidence and the clinical findings, presented in simple tables that outline potential benefits including Patient Reported Outcome Measures (PROMs). This approach enables clinicians to assess clinical relevance and researchers to identify significant gaps in the literature. The first part provides a comprehensive summary of the basic science surrounding APC, with particular focus on their preparation methods. Clear recommendations are outlined, which are crucial for obtaining high‐quality APCs, alongside an exploration of how APCs may influence both soft and hard tissue healing processes. Part 2 delves into the clinical evidence for the potential benefits of APCs across a range of applications: alveolar ridge preservation, sinus floor elevation, periodontal plastic surgery, guided tissue regeneration, guided bone regeneration, the healing of Medication‐Related Osteonecrosis of the Jaw (MRONJ), and endodontic surgery. In the part 3, the discussion turns to the effects of APCs on the healing of extra‐oral wounds, including diabetic foot ulcers, venous leg ulcers, pressure injuries, burns, and more. The fourth section offers a detailed, step‐by‐step flowchart for each treatment modality, providing a clear guide for clinical application.
A Visibility‐Based Multitree of a Space Subdivision for Indoor Localization
Authors: Aleksandrov Mitko , Amoozandeh Kimia , Winter Stephan , Zlatanova Sisi , Tomko Martin
Published: September 2024

In an era where localization is increasingly vital for daily activities, determining an individual's location and providing suggestions is crucial for successful navigation. Central to our method is the concept of visibility areas, defined as spaces from which a landmark is at least partially visible. We tessellate space into a grid and use raycasting to determine these visibility areas. Visibility areas are further subdivided into sub‐spaces, each representing a unique set of visible landmarks. To efficiently manage and query these sub‐spaces, we create a tree of options for each landmark and merge them into one compact multitree. This structure represents a hierarchical composition of sub‐spaces and enhances query efficiency while storing each sub‐space only once in the memory. The multitree is designed to support the rapid identification of sub‐spaces based on observed landmarks, resulting in efficient localization within the environment is presented to calculating the optimal localization point in a visibility area based on suggested visible landmarks. The paper concludes with a discussion of the approach targeting indoor localization but highlights also its potential for further research and some limitations.
Trait association and prediction through integrative k‐mer analysis
Authors: He Cheng , Washburn Jacob D. , Schleif Nathaniel , Hao Yangfan , Kaeppler Heidi , Kaeppler Shawn M. , Zhang Zhiwu , Yang Jinliang , Liu Sanzhen
Published: September 2024

Genome‐wide association study (GWAS) with single nucleotide polymorphisms (SNPs) has been widely used to explore genetic controls of phenotypic traits. Alternatively, GWAS can use counts of substrings of length k from longer sequencing reads, k‐mers, as genotyping data. Using maize cob and kernel color traits, we demonstrated that k‐mer GWAS can effectively identify associated k‐mers. Co‐expression analysis of kernel color k‐mers and genes directly found k‐mers from known causal genes. Analyzing complex traits of kernel oil and leaf angle resulted in k‐mers from both known and candidate genes. A gene encoding a MADS transcription factor was functionally validated by showing that ectopic expression of the gene led to less upright leaves. Evolution analysis revealed most k‐mers positively correlated with kernel oil were strongly selected against in maize populations, while most k‐mers for upright leaf angle were positively selected. In addition, genomic prediction of kernel oil, leaf angle, and flowering time using k‐mer data resulted in a similarly high prediction accuracy to the standard SNP‐based method. Collectively, we showed k‐mer GWAS is a powerful approach for identifying trait‐associated genetic elements. Further, our results demonstrated the bridging role of k‐mers for data integration and functional gene discovery.
Placemaking in the nuclear sensorium
Authors: Lusztig Irene , Cram Shannon
Published: September 2024

This dialogue considers Irene Lusztig's 2023 film Richland, a place‐based documentary about a nuclear company town in southeastern Washington State. Built by the US government as part of the Manhattan Project, Richland fueled thousands of weapons in the nation's nuclear arsenal, including the bomb dropped on Nagasaki, Japan. Lusztig speaks with interdisciplinary scholar Shannon Cram about how this community inhabits the complex and contradictory relations of atomic violence and nuclear pride. So too, they discuss Lusztig's listening‐centered documentary method with a specific focus on what it means to facilitate listening across political and ideological difference.
Bioreactance noninvasive cardiac output monitoring in euvolemic adult horses subjected with 7.2% saline and 6% hydroxyethyl starch (130/0.4) solution infusions
Authors: Long Alicia E. , Hurcombe Samuel , Hopster Klaus
Published: September 2024

Objective

To compare the ability of bioreactance noninvasive cardiac output (BR‐NICO) with thermodilution cardiac output (TDCO) for the measurement of cardiac output (CO) in healthy adult horses receiving 2 different IV volume replacement solutions.

Design

Prospective randomized crossover study from September to November 2021.

Setting

University teaching hospital.

Animals

Six university‐owned adult horses.

Interventions

Horses were randomly assigned to receive 7.2% hypertonic saline solution (HSS) or 6% hydroxyethyl starch (130/0.4) solution (HETA). BR‐NICO and TDCO were measured simultaneously at baseline, 10, 20, 30, 40, 50, 60, 90, and 120 minutes before fluid administration and again at the same times after starting a bolus infusion of IV volume replacers. All solutions were administered within 10 minutes.

Measurements and Main Results

BR‐NICO and TDCO were strongly correlated (Pearson r2 = 0.93; P < 0.01). Regression analysis showed the relationship between TDCO and BR‐NICO was BR‐NICO = 0.48 × TDCO + 0.6. For the corrected BR‐NICO values, the Bland–Altman agreement mean bias and lower/upper limits of agreement were −0.62 and −5.3 to 3.9 L/min, respectively. Lin's concordance (95% confidence interval) between methods was 0.894 (0.825–1.097). Compared with baseline, HSS increased the CO at 10 and 20 minutes (TDCO and BR‐NICO). Compared with baseline, HETA decreased the CO at 10 and 20 minutes (TDCO and BR‐NICO) and increased the CO at 90 (TDCO only) and 120 minutes (TDCO and BR‐NICO).

Conclusions

BR‐NICO strongly agreed with TDCO in the measurement of CO in healthy unsedated adult horses. HSS administration significantly increased CO in the first 30 minutes, while HETA initially decreased CO at 10 minutes but increased CO to above baseline values by 90 minutes.
Description of a new genus and species of deep‐sea mysids (Malacostraca, Peracarida, Mysida) from the Caroline Ridge, Northwest Pacific, with a systematic analysis of the order
Authors: Kou Qi , Meland Kenneth , Li Xinzheng
Published: September 2024

The order Mysida Boas, 1883 is a group of small, shrimp‐like peracarid crustaceans with surprisingly high morphological and ecological diversity. In this study, a new genus and species of deep‐sea mysids, Muscamysis carolinensis gen. et sp. n., is described based on a solitary specimen recently collected from the Caroline Ridge, Northwest Pacific. To determine the phylogenetic position of the new genus within Mysida, we reconstruct a comprehensive multi‐gene phylogeny of the order, incorporating 45 species from 10 sub‐families and two families. Our analysis reveals strong support for a close relationship between the new genus and Mysidellinae Czerniavsky, 1882, with both forming a clade nested within Heteromysinae Norman, 1892. Notably, our findings do not support the current delineation or monophyly of most mysid sub‐families, emphasizing the necessity for further taxonomic revisions. Specifically, Palaumysinae Wittmann, 2013 is now synonymized with Erythropinae Hansen, 1910, while Heteromysinae is synonymized with Mysidellinae. Bayesian divergence time estimation uncovers, for the first time, multiple independent coastal subterranean colonizations of mysids during the Mesozoic. Ancestral state reconstruction analyses suggest that characters, such as the cleft telson and reduced male pleopods, are the results of parallel evolution, indicating that certain diagnostic characters may not be apomorphic, thereby necessitating more substantial revisions to the current higher‐level classification of the order.
Laurent family of simple modules over quiver Hecke algebras
Authors: Kashiwara Masaki , Kim Myungho , Oh Se-jin , Park Euiyong
Published: September 2024

We introduce the notions of quasi-Laurent and Laurent families of simple modules over quiver Hecke algebras of arbitrary symmetrizable types. We prove that such a family plays a similar role of a cluster in quantum cluster algebra theory and exhibits a quantum Laurent positivity phenomenon similar to the basis of the quantum unipotent coordinate ring $\mathcal {A}_q(\mathfrak {n}(w))$, coming from the categorification. Then we show that the families of simple modules categorifying Geiß–Leclerc–Schröer (GLS) clusters are Laurent families by using the Poincaré–Birkhoff–Witt (PBW) decomposition vector of a simple module $X$ and categorical interpretation of (co)degree of $[X]$. As applications of such $\mathbb {Z}\mspace {1mu}$-vectors, we define several skew-symmetric pairings on arbitrary pairs of simple modules, and investigate the relationships among the pairings and $\Lambda$-invariants of $R$-matrices in the quiver Hecke algebra theory.
Acute exercise alters brain glucose metabolism in aging and Alzheimer's disease
Authors: Green Zachary D. , John Casey S. , Kueck Paul J. , Blankenship Anneka E. , Kemna Riley E. , Johnson Chelsea N. , Yoksh Lauren E. , Best Shaun R. , Donald Joseph S. , Mahnken Jonathan D. , Burns Jeffrey M. , Vidoni Eric D. , Morris Jill K.
Published: September 2024

There is evidence that aerobic exercise improves brain health. Benefits may be modulated by acute physiological responses to exercise, but this has not been well characterized in older or cognitively impaired adults. The randomized controlled trial ‘AEROBIC’ (NCT04299308) enrolled 60 older adults who were cognitively healthy (n = 30) or cognitively impaired (n = 30) to characterize the acute brain responses to moderate [45–55% heart rate reserve (HRR)] and higher (65–75% HRR) intensity acute exercise. Each participant received two fluorodeoxyglucose positron emission tomography (FDG‐PET) scans, one at rest and one following acute exercise. Change in cerebral glucose metabolism from rest to exercise was the primary outcome. Blood biomarker responses were also characterized as secondary outcomes. Whole grey matter FDG‐PET standardized uptake value ratio (SUVR) differed between exercise (1.045 ± 0.082) and rest (0.985 ± 0.077) across subjects [Diff = −0.060, t(58) = 13.8, P < 0.001] regardless of diagnosis. Exercise increased lactate area under the curve (AUC) [F(1,56) = 161.99, P < 0.001] more in the higher intensity group [mean difference (MD) = 97.0 ± 50.8] than the moderate intensity group (MD = 40.3 ± 27.5; t = −5.252, P < 0.001). Change in lactate AUC and FDG‐PET SUVR correlated significantly (R2 = 0.179, P < 0.001). Acute exercise decreased whole grey matter cerebral glucose metabolism. This effect tracked with the systemic lactate response, suggesting that lactate may serve as a key brain fuel during exercise. Direct measurements of brain lactate metabolism in response to exercise are warranted.

image

Key points

Acute exercise is associated with a drop in global brain glucose metabolism in both cognitively healthy older adults and those with Alzheimer's disease.

Blood lactate levels increase following acute exercise.

Change in brain metabolism tracks with blood lactate, suggesting it may be an important brain fuel.

Acute exercise stimulates changes in brain‐derived neurotrophic factor and other blood biomarkers.
Rapid Airborne Gas-Plume Mapping and Source Localization With Feedforward Gas-Sensor Dynamics Compensation
Authors: Hoffman Kyle C. , Anderson Jacob M. , Leang Kam K.
Published: September 2024

This article focuses on improving the speed, accuracy, and robustness of autonomous aerial-based chemical sensing for plume mapping and source localization through characterizing, modeling, and feedforward compensation of gas-sensor dynamics. First, the dynamics of three types of gas sensors are modeled. Second, the maximum chemical-mapping speed is calculated and shown to be inversely proportional to sensor time constant. Third, an inversion-based approach is used to compensate for the sensor dynamics to improve mapping throughput. Results show that dynamics compensation enhances the chemical-mapping speed by over five times compared to the uncompensated case. Finally, to further demonstrate utility, the approach is applied to a particle swarm optimization example for plume-source localization. The improvement is observed by how well the agents converge to the true chemical gas source location when gas-sensor dynamics are taken into account. Specifically, for a static Gaussian plume source, feedforward compensation leads to 64% average improvement in localization success, and for a dynamic Quick Urban and Industrial Complex (QUIC) dispersion plume source, a 39% average improvement is observed. These results underscore the importance of sensor dynamics compensation for enhancing mapping and source localization throughput, accuracy, and robustness.
An Investigation into the Viability of Cell-Level Temperature Control in Lithium-Ion Battery Packs
Authors: Abadie Preston T. , Docimo Donald J.
Published: September 2024

This article focuses on the thermal management and temperature balancing of lithium-ion battery packs. As society transitions to relying more heavily on renewable energy, the need for energy storage rises considerably, as storage facilitates power regulation between these sources and the grid. Lithium-ion batteries are leading the market for energy storage options, but their properties are temperature sensitive, with thermal abuse resulting in shortened pack lifetime and possible safety issues. Current battery thermal management systems (BTMS) are implemented in a number of ways to ensure consistent and reliable operation. However, they are typically limited in architecture and restricted in ability to attend to temperature gradients. This work proposes a BTMS topology that permits control of the individual cooling received by a cell in a pack. First, an analysis is done using timescale separation to confirm that cell-level temperature control is capable of extending the lifetime of a pack as compared to pack-level control. The analysis is used to guide the gain tuning of a state feedback controller, which directs more cooling effort to cells of higher temperatures. Validation of the BTMS topology and control is performed through the simulation of a battery pack, with variations in total cooling power and resistance heterogeneity. The outcome of the validation studies indicates that the proposed BTMS configuration is better equipped to reduce temperature differences and extend pack life. This benefit increases as total input power increases, giving the controller more freedom to cool unhealthy cells while remaining within power constraints.
High-Speed 50,000 rpm Planetary Roller Reducer for Electric Vehicles: Design and Transmission Efficiency Analysis
Authors: Yamamoto Takeshi , Miura Yoshitaka , Matsushita Yuuki , Hashimoto Shin
Published: September 2024

Planetary rollers produce no meshing vibration and exhibit low noise, so that they are suitable for use as reducers for high-speed electric motors. On the other hand, at high rotational speeds of tens of thousands of rpm, there is a concern that the transmission efficiency may decrease due to oil churning resistance in the traction portion and the bearings, windage associated with the rollers, and rolling viscous resistance in the traction portion. However, accurate transmission efficiency at high rotational speeds has not been measured, and loss factors have not been analyzed. Therefore, a planetary roller prototype and a high-speed tester were designed and manufactured, and transmission efficiency measurements at speeds of up to 50,000 rpm were performed. In addition, a model was constructed to calculate the loss caused by the load and rotation of each part that configures the reducer, and the calculations were confirmed to agree well with the experimental results. It was clarified that the planetary roller prototype has a high transmission efficiency of up to 98%, that the decrease in efficiency is small even at high rotational speeds, and that the spin loss due to the bearings and churning is small.
Parallel gain modulation mechanisms set the resolution of color selectivity in human visual cortex
Authors: Schulz Marie-Christin , Bartsch Mandy V. , Merkel Christian , Strumpf Hendrik , Schoenfeld Mircea A. , Hopf Jens-Max
Published: September 2024

Color discrimination is fundamental to human behavior. We find bananas by coarsely searching for yellow but then differentiate nuances of yellow to pick the best exemplars. How does the brain adjust the resolution of color selectivity to our changing needs? Here, we analyze the brain magnetic response in the human visual cortex to show that color selectivity is adaptively set by coarse- and fine-resolving processes running in parallel at different hierarchical levels. Those include a gain enhancement in the higher-lever cortex of color units tuned away from the target to resolve very similar colors and a coarsely resolving gain enhancement in the mid-level cortex of units tuned to the target. Our findings suggest that attention operates on a form of multiresolution representation of color at different levels in the visual hierarchy, which keeps selectivity adaptive to a changing resolution context.
Antibiotics damage the colonic mucus barrier in a microbiota-independent manner
Authors: Sawaed Jasmin , Zelik Lilach , Levin Yehonatan , Feeney Rachel , Naama Maria , Gordon Ateret , Zigdon Mor , Rubin Elad , Telpaz Shahar , Modilevsky Sonia , Ben-Simon Shira , Awad Aya , Harshuk-Shabso Sarina , Nuriel-Ohayon Meital , Werbner Michal , Schroeder Bjoern O. , Erez Amir , Bel Shai
Published: September 2024

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.
Multiscale crack trapping for programmable adhesives
Authors: Park Seongjin , Kang Dong Kwan , Lee Donghyuk , Choi Geonjun , Kim Jaeil , Lee Chanhong , Seong Minho , Bartlett Michael D. , Jeong Hoon Eui
Published: September 2024

The precise control of crack propagation at bonded interfaces is crucial for smart adhesives with advanced performance. However, previous studies have primarily concentrated on either microscale or macroscale crack propagation. Here, we present a hybrid adhesive that integrates microarchitectures and macroscopic nonlinear cut architectures for unparalleled adhesion control. The integration of these architectural elements enables conformal attachment and simultaneous crack trapping across multiple scales for high capacity, enhancing adhesion by more than 70×, while facilitating crack propagation at the macroscale in specific directions for programmable release and reusability. As adhesion strength and directionality can be independently controlled at any location, skin adhesive patches are created that are breathable, nondamaging, and exceptionally strong and secure yet remove easily. These capabilities are demonstrated with a skin-mounted adhesive patch with integrated electronics that accurately detects human motion and wirelessly transmits signals, enabling real-time control of avatars in virtual reality applications.
Stretchable Arduinos embedded in soft robots
Authors: Woodman Stephanie J. , Shah Dylan S. , Landesberg Melanie , Agrawala Anjali , Kramer-Bottiglio Rebecca
Published: September 2024

To achieve real-world functionality, robots must have the ability to carry out decision-making computations. However, soft robots stretch and therefore need a solution other than rigid computers. Examples of embedding computing capacity into soft robots currently include appending rigid printed circuit boards to the robot, integrating soft logic gates, and exploiting material responses for material-embedded computation. Although promising, these approaches introduce limitations such as rigidity, tethers, or low logic gate density. The field of stretchable electronics has sought to solve these challenges, but a complete pipeline for direct integration of single-board computers, microcontrollers, and other complex circuitry into soft robots has remained elusive. We present a generalized method to translate any complex two-layer circuit into a soft, stretchable form. This enabled the creation of stretchable single-board microcontrollers (including Arduinos) and other commercial circuits (including SparkFun circuits), without design simplifications. As demonstrations of the method’s utility, we embedded highly stretchable (>300% strain) Arduino Pro Minis into the bodies of multiple soft robots. This makes use of otherwise inert structural material, fulfilling the promise of the stretchable electronic field to integrate state-of-the-art computational power into robust, stretchable systems during active use.
Targeted partial reprogramming of age-associated cell states improves markers of health in mouse models of aging
Authors: Sahu Sanjeeb Kumar , Reddy Pradeep , Lu Jinlong , Shao Yanjiao , Wang Chao , Tsuji Mako , Delicado Estrella Nuñez , Rodriguez Esteban Concepcion , Belmonte Juan Carlos Izpisua
Published: September 2024

Aging is a complex multifactorial process associated with epigenome dysregulation, increased cellular senescence, and decreased rejuvenation capacity. Short-term cyclic expression of
octamer-binding transcription factor 4
(
Oct4
),
sex-determining region Y-box 2
(
Sox2
),
Kruppel-like factor 4
(
Klf4
), and
cellular myelocytomatosis oncogene
(
cMyc
) (
OSKM
) in wild-type mice improves health but fails to distinguish cell states, posing risks to healthy cells. Here, we delivered a single dose of adeno-associated viruses (AAVs) harboring
OSK
under the control of the
cyclin-dependent kinase inhibitor 2a
(
Cdkn2a
) promoter to specifically partially reprogram aged and stressed cells in a mouse model of Hutchinson-Gilford progeria syndrome (HGPS). Mice showed reduced expression of proinflammatory cytokines and extended life spans upon aged cell–specific
OSK
expression. The bone marrow and spleen, in particular, showed pronounced gene expression changes, and partial reprogramming in aged HGPS mice led to a shift in the cellular composition of the hematopoietic stem cell compartment toward that of young mice. Administration of AAVs carrying
Cdkn2a-OSK
to naturally aged wild-type mice also delayed aging phenotypes and extended life spans without altering the incidence of tumor development. Furthermore, intradermal injection of AAVs carrying
Cdkn2a
-

OSK

led to improved wound healing in aged wild-type mice. Expression of
CDKN2A
-
OSK
in aging or stressed human primary fibroblasts led to reduced expression of inflammation-related genes but did not alter the expression of cell cycle–related genes. This targeted partial reprogramming approach may therefore facilitate the development of strategies to improve health and life span and enhance resilience in the elderly.
HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis
Authors: Jeelani Ishtiaq , Moon Jae-Su , da Cunha Flavia Franco , Nasamran Chanond A. , Jeon Seokhyun , Zhang Xinhang , Bandyopadhyay Gautam K. , Dobaczewska Katarzyna , Mikulski Zbigniew , Hosseini Mojgan , Liu Xiao , Kisseleva Tatiana , Brenner David A. , Singh Seema , Loomba Rohit , Kim Minkyu , Lee Yun Sok
Published: September 2024

Proinflammatory hepatic macrophage activation plays a key role in the development of nonalcoholic steatohepatitis (NASH). This involves increased embryonic hepatic Kupffer cell (KC) death, facilitating the replacement of KCs with bone marrow–derived recruited hepatic macrophages (RHMs) that highly express proinflammatory genes. Moreover, phago/efferocytic activity of KCs is diminished in NASH, enhancing liver inflammation. However, the molecular mechanisms underlying these changes in KCs are not known. Here, we show that hypoxia-inducible factor 2α (HIF-2α) mediates NASH-associated decreased KC growth and efferocytosis by enhancing lysosomal stress. At the molecular level, HIF-2α stimulated mammalian target of rapamycin (mTOR)– and extracellular signal–regulated kinase-dependent inhibitory transcription factor EB (TFEB) phosphorylation, leading to decreased lysosomal and phagocytic gene expression. With increased metabolic stress and phago/efferocytic burden in NASH, these changes were sufficient to increase lysosomal stress, causing decreased efferocytosis and lysosomal cell death. Of interest, HIF-2α–dependent TFEB regulation only occurred in KCs but not RHMs. Instead, in RHMs, HIF-2α promoted mitochondrial reactive oxygen species production and proinflammatory activation by increasing ANT2 expression and mitochondrial permeability transition. Consequently, myeloid lineage–specific or KC-specific HIF-2α depletion or the inhibition of mTOR-dependent TFEB inhibition using antisense oligonucleotide treatment protected against the development of NASH in mice. Moreover, treatment with an HIF-2α–specific inhibitor reduced inflammatory and fibrogenic gene expression in human liver spheroids cultured under a NASH-like condition. Together, our results suggest that macrophage subtype–specific effects of HIF-2α collectively contribute to the proinflammatory activation of liver macrophages, leading to the development of NASH.
BATF is a major driver of NK cell epigenetic reprogramming and dysfunction in AML
Authors: Kumar Bijender , Singh Anand , Basar Rafet , Uprety Nadima , Li Ye , Fan Huihui , Cortes Ana Karen Nunez , Kaplan Mecit , Acharya Sunil , Shaim Hila , Xu Anna C , Wu Manrong , Ensley Emily , Fang Dexing , Banerjee Pinaki P. , Garcia Luciana Melo , Tiberti Silvia , Lin Paul , Rafei Hind , Munir Maliha Nuzhat , Moore Madison , Shanley Mayra , Mendt Mayela , Kerbauy Lucila N. , Liu Bin , Biederstädt Alexander , Gokdemir Elif , Ghosh Susmita , Kundu Kiran , Reyes-Silva Francia , Jiang Xin Ru , Wan Xinhai , Gilbert April L. , Dede Merve , Mohanty Vakul , Dou Jinzhuang , Zhang Patrick , Liu Enli , Muniz-Feliciano Luis , Deyter Gary M. , Jain Abhinav K. , Rodriguez-Sevilla Juan Jose , Colla Simona , Garcia-Manero Guillermo , Shpall Elizabeth J. , Chen Ken , Abbas Hussein A. , Rai Kunal , Rezvani Katayoun , Daher May
Published: September 2024

Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism, and an exhausted phenotype at the single-cell transcriptomic and proteomic levels. In this study, we identified that this dysfunction was mediated through a cross-talk between NK cells and myeloid blasts necessitating cell-cell contact. NK cell dysfunction could be prevented by targeting the αvβ-integrin/TGF-β/SMAD pathway but, once established, was persistent because of profound epigenetic reprogramming. We identified BATF as a core transcription factor and the main mediator of this NK cell dysfunction in AML. Mechanistically, we found that BATF was directly regulated and induced by SMAD2/3 and, in turn, bound to key genes related to NK cell exhaustion, such as
HAVCR2
,
LAG3
,
TIGIT
, and
CTLA4
. BATF deletion enhanced NK cell function against AML in vitro and in vivo. Collectively, our findings reveal a previously unidentified mechanism of NK immune evasion in AML manifested by epigenetic rewiring and inactivation of NK cells by myeloid blasts. This work highlights the importance of using healthy allogeneic NK cells as an adoptive cell therapy to treat patients with myeloid malignancies combined with strategies aimed at preventing the dysfunction by targeting the TGF-β pathway or BATF.
HIV-induced RSAD2/Viperin supports sustained infection of monocyte-derived macrophages
Authors: Zankharia Urvi , Yi Yanjie , Lu Fang , Vladimirova Olga , Karisetty Bhanu Chandra , Wikramasinghe Jayamanna , Kossenkov Andrew , Collman Ronald G. , Lieberman Paul M.
Published: September 2024

HIV establishes long-term latent infection in memory CD4
+
T cells and also establishes sustained long-term productive infection in macrophages, especially in the central nervous system (CNS). To better understand how HIV sustains infection in macrophages, we performed RNAseq analysis after infection of human monocyte-derived macrophages (MDMs) with the brain-derived HIV-1 strain YU2 and compared this with acute infection of CD4
+
T cells. HIV infection in MDM and CD4
+
T cells altered many gene transcripts, but with few overlaps between these different cell types. We found interferon pathways upregulated in both MDM and CD4
+
T cells, but with different gene signatures. The interferon-stimulated gene RSAD2/Viperin was among the most upregulated genes following HIV infection in MDMs, but not in CD4
+
T cells. RSAD2/Viperin was induced early after infection with various HIV strains, was sustained over time, and remained elevated in established MDM infection even if new rounds of infection were blocked by antiretroviral treatment. Immunofluorescence microscopy revealed that RSAD2/Viperin was induced in HIV-infected cells, as well as in some uninfected neighboring cells. Knockdown of RSAD2/Viperin following the establishment of infection in MDMs reduced the production of HIV transcripts and viral p24 antigen. This correlated with the reduction in the number of multinucleated giant cells, and changes in the HIV DNA and chromatin structure, including an increased DNA copy number and loss of nucleosomes and histone modifications at the long terminal repeat (LTR). RNAseq transcriptomic analysis of RSAD2/Viperin knockdown during HIV infection of MDMs revealed the activation of interferon alpha/beta and gamma pathways and the inactivation of Rho GTPase pathways. Taken together, these results suggest that RSAD2/Viperin supports the sustained infection in macrophages, potentially through mechanisms involving the alteration of the LTR chromatin structure and the interferon response.

IMPORTANCE

HIV infection of macrophages is a barrier to HIV cure and a source of neurocognitive pathology. We found that HIV induces RSAD2/Viperin during sustained infection of macrophages. While RSAD2/Viperin is an interferon-stimulated gene with known antiviral activity, we find RSAD2/Viperin promotes HIV infection in macrophages through multiple mechanisms, including interferon signaling. Therefore, RSAD2/Viperin may be a therapeutic target for the treatment of HIV-infected macrophages.
Divergence of rhizosphere microbial communities between females and males of the dioecious
Hippophae tibetana
at different habitats
Authors: Mao YiFan , Li Ni , Huang YaLi , Chen DaWei , Sun Kun
Published: September 2024

Females and males of dioecious plants have evolved sex-specific characteristics in terms of their morphological and physiological properties. However, little is known about the difference in rhizosphere microbes in dioecious plants. In this study, we used amplicon sequencing to analyze the differences in rhizosphere microbial diversity and community composition of males and females of dioecious
Hippophae tibetana
at different habitats, and their key factors in driving the differences were investigated. The results showed that there were differences in the diversity, community composition, and connectivity and complexity of the co-occurrence network of rhizosphere microbes between females and males of the dioecious
H. tibetana
at different habitats. Zoopagomycota is a unique phylum of rhizosphere fungi in the males of the dioecious
H. tibetana
, while Dependentiae is a unique phylum of rhizosphere bacteria in the females of the dioecious
H. tibetana
. Linear discriminant analysis effect size (LEfSe) analysis indicated significant enrichment of species at different levels, suggesting that these species could be potential biomarkers for females and males of
H. tibetana
. Spearman’s analysis showed that the dominant genera of rhizosphere fungi were significantly positively correlated with soil physicochemical properties (total nitrogen and phosphorus; organic matter; available phosphorus, potassium and nitrogen; salt content; water content). PICRUSt and FUNGuild predictive analysis indicated that the function of rhizosphere fungi was different between females and males of the dioecious
H. tibetana
at different habitats, while metabolites were the dominant functions of rhizosphere bacteria in all samples. These results highlighted the sexual discrimination of rhizosphere microbes on the dioecious plants and provided important knowledge for females and males of the dioecious plant–microbe interaction.

IMPORTANCE

This study explores the differences in rhizosphere microbes of dioecious
Hippophae tibetana
at different habitats and their key factors in driving the differences. Through employing amplicon sequencing techniques, we found that rhizosphere microbial communities and diversity were different between females and males of the dioecious
H. tibetana
at different habitats, and there notably existed unique phylum and potential biomarkers of rhizosphere microbes between females and males of the dioecious
H. tibetana
. Rhizosphere fungi were significantly positively correlated with soil physicochemical properties. This study reveals the differences in rhizosphere microbes of dioecious
H. tibetana
at different habitats and driving factors; it also contributes to our understanding of the dioecious plant–microbe interaction.
Supplemental Material: The geometry of fault reactivation and uplift along the central part of the Maacama Fault Zone, Northern California Coast Ranges
Authors: Melosh Benjamin , al. et
Published: September 2024

.dxf files of the Maacama Fault, Ukiah Valley Fault, and Cow Mountain–Mill Creek Fault from Figure 11.  
Supplemental Material: Provenance of the Mesoproterozoic Shennongjia Group in the north Yangtze Block, South China, and implications for reconstructions of the Nuna and Rodinia supercontinents
Authors: Yang Jie , Hu Lisha , al. et
Published: September 2024

Table S1: U-Pb isotopic compositions of detrital zircons from the mid-Mesoproterozoic Taizi (TZ1–TZ3) and Luanshigou (T2370–T2375) formations of the Shennongjia Group. Table S2: Trace elemental concentrations of detrital zircons from the mid-Mesoproterozoic Taizi (TZ1–TZ3) and Luanshigou (T2370–T2375) formations of the Shennongjia Group. Table S3: Hf isotopic compositions of detrital zircons from the mid-Mesoproterozoic Taizi and Luanshigou formations of the Shennongjia Group. Table S4: Zircon U-Pb geochronological data used for the manuscript’s figures and analyses. Table S5: Hf isotopic data used for the manuscript’s figures and analyses.
Metformin-associated lactic acidosis: a serious complication of a common drug
Authors: Malani Kanika Ajay , Finn Arkadiy
Published: September 2024

Metformin-associated lactic acidosis (MALA) is a rare and potentially life-threatening complication of metformin use. It typically occurs in patients who are diabetic and also have other risk factors for lactic acidosis, including kidney and liver conditions, malignancy, or use of certain medications. We report a case of MALA in a man in his 70s with diabetes who presented with gradually worsening gastrointestinal symptoms, including severe abdominal pain and nausea. He reported these symptoms in the setting of metformin use with an acute kidney injury (AKI), likely brought on by poor oral intake and excessive antibiotic use for a urinary tract infection. He was promptly started on intravenous fluids with a bicarbonate drip to concurrently treat his prerenal AKI and lactic acidosis, which resulted in rapid resolution of his symptoms. Renal function normalised within 12 days of admission. Since diabetic patients commonly use metformin and are also at higher risk of renal dysfunction, this case highlights the vulnerability of this group of patients and the need for increased knowledge and awareness of MALA.
Stated preferences of adolescents and young adults for sexual and reproductive health services in Africa: a systematic review protocol
Authors: Alemu Melaku Birhanu , Norman Richard , Dantas Jaya , Belay Daniel Gashaneh , Pereira Gavin , Tessema Gizachew A
Published: September 2024

Background

Adolescence and young adulthood are critical life stages with varied healthcare needs. Adolescents and young adults (AYAs) are often confronted with challenges in their sexual and reproductive health (SRH) and rights. Uptake of SRH services among AYAs groups remains limited, especially in resource-limited settings. This could be partly attributed to the existing services not catering for the preferences of AYAs. However, there is no systematic evaluation of research to explore the preferences of AYAs for SRH services in Africa. Therefore, the objective of this systematic review is to assess AYAs’s preferences for SRH in Africa.

Methods and analysis

The systematic review will follow the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. Stated preference studies in the area of SRH services conducted among AYAs will be included. We will search MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, Global Health and Google Scholar databases. Two independent researchers will screen the articles, and any disagreement will be handled through discussion with the broader research team. The quality of the included papers will be assessed and reported. The preferences for attributes, the most important and least important attributes and preference heterogeneity will be reported. In addition, the preference research gap across African regions and SRH services among AYAs will be reported.

Ethics and dissemination

Ethical approval is not required for this protocol. The systematic review findings will be published in a peer-reviewed journal and presented at conferences.

PROSPERO registration number

CRD42023386944.