bluuebunny/crossref_metadata_2025_split huggingface dataset:
Season of drought affects growth, but not nonstructural carbohydrates dynamics, in Pinus taeda saplings
Authors: Oswald Scott W , Aubrey Doug P 
Published: February 2024

Abstract
In temperate evergreen conifers, growth occurs mostly in summer but photosynthesis proceeds year-round; thus, nonstructural carbohydrates (NSCs) increase in winter but decrease in summer. Given that mild drought reduces growth but not photosynthesis, a drought in summer should increase NSCs more than one in winter. However, the active regulation hypothesis suggests that to increase future drought resilience, plants might downregulate growth to increase NSCs after a winter drought even if NSCs do not increase during the drought. To test whether this is so, potted Pinus taeda saplings (age $&lt;\kern-3pt1$ year) were subjected to 6-month droughts in a greenhouse with one treatment receiving drought during winter (September–March), and another during summer (March–September). Both treatments were compared with a control. To measure dry biomass and NSCs, we harvested plants monthly following each drought, while to assess changes in growth rates, we measured height and diameter monthly. While we observed seasonal variation and an overall increase during the study, we found no drought-related changes in NSC dynamics; however, drought did reduce growth. Furthermore, drought in winter did reduce growth during the following summer, but the reduction was less than for a drought in summer. We conclude that the effect of drought on NSCs was too small to detect in our plants. While better control of soil water would have reduced a major source of uncertainty, plants with larger NSC reserves or more intense stress would also yield easier-to-detect effects. Although not definitive, our results suggest that water stress does not lead to dramatic changes in seasonal NSC dynamics in its aftermath, despite what one might expect under the active regulation hypothesis.
Imaging and clinical features of pulsatile polypoidal choroidal vasculopathy
Authors: Choi Kwang-Eon , Lee Young Joo , Bae So Hyeon 
Published: February 2024

Purpose:
To investigate the imaging and clinical features of polypoidal choroidal vasculopathy (PCV) with the pulsation.

Methods:
The PCV eyes were classified into pulsatile and non-pulsatile PCV groups according to the pulsation on indocyanine green angiography (ICGA). Imaging features including the dye filling time of the polyp and clinical features were compared.

Results:
A total of 75 eyes were classified into the pulsatile PCV (30 eyes) or the non-pulsatile PCV (45 eyes) groups. The initial and complete filling time of the polyp of the pulsatile PCV group (2.59 ± 0.93 and 8.33 ± 3.42 seconds) were shorter than those of the non-pulsatile PCV group (4.11 ± 1.87 and 10.63 ± 3.81 seconds, p < 0.001 and p = 0.010, respectively). Pigment epithelial detachment (PED) height of the pulsatile PCV group (414.90 ± 377.15 µm) was greater than that of the non-pulsatile PCV group (247.81 ± 164.07 µm, p = 0.030). Pulsatile PCV group showed a higher prevalence of subretinal hemorrhage (43.33%) after intravitreal injection than non-pulsatile PCV group (13.95%, p = 0.005) during 12 months. The mean number of injections during 12 months of the pulsatile PCV group (5.48 ± 1.46) was greater than that of the non-pulsatile PCV group (4.09 ± 1.21, p < 0.001).

Conclusion:
Eyes with pulsatile PCV showed shorter filling time of the polyp, greater PED height, higher prevalence of subretinal hemorrhage, and more intravitreal injection numbers during 12 months. These might suggest that PCV has distinct imaging and clinical features according to the polyp pulsation.
Resting-state Functional Connectivity Predicts Cochlear-Implant Speech Outcomes
Authors: Esmaelpoor Jamal , Peng Tommy , Jelfs Beth , Mao Darren , Shader Maureen J. , McKay Colette M. 
Published: February 2024

AbstractBackgroundCochlear implants (CIs) have revolutionized hearing restoration for individuals with severe or profound hearing loss. However, a substantial and unexplained variability persists in CI outcomes, even when considering subject-specific factors such as age and the duration of deafness. In this study, we explore the utility of resting-state functional near-infrared spectroscopy (fNIRS) recordings to predict speech understanding outcomes before and after CI implantation. Our hypothesis revolves around resting-state functional connectivity (FC) as a reflection of brain plasticity post-hearing loss and implantation. Specifically, we hypothesized that the average clustering coefficient in resting FC networks can capture this variation among CI users.MethodsTwenty-two cochlear implant candidates participated in this study. Resting-state fNIRS data were collected pre-implantation and at one month, three months, and one year post-implantation. Speech understanding performance was assessed using CNC words in quiet and BKB sentences in noise one year post-implantation. Resting-state functional connectivity networks were constructed using regularized partial correlation, and the average clustering coefficient was measured in the signed weighted networks as a predictive measure for implantation outcomes.ResultsOur findings demonstrate a significant correlation between the average clustering coefficient in resting-state functional networks and speech understanding outcomes. Importantly, our analysis reveals that this measure provides unique information not accounted for by subject-specific factors such as age and duration of deafness.ConclusionThis approach utilizes an easily deployable resting-state functional brain imaging metric to predict speech understanding outcomes in implant recipients. The results indicate that the average clustering coefficient, both pre and post implantation, correlates with speech understanding outcomes.
Renal Profile of Herbal Medicine Users versus Non-users: an Exploratory Cross-sectional Study in a Family Medicine Clinic in Nigeria
Authors: Maiyegun Afisulahi Abiodun , Akangoziri Mark Divine , Grema Bukar Alhaji , Mutalub Yahkub Babatunde , Ibrahim Farida Buhari 
Published: February 2024

ABSTRACTBackgroundA major risk of herbal medicine is the potential for toxicity and serious side effects. Unlike orthodox medicine, herbs are usually consumed without prior safety assessment via clinical studies. This means the clinical effects of herbs may be detected only through an assessment of health parameters of consumers.ObjectiveTo evaluate participants’ renal profile, comparing that of herb users with non-users, thereby identifying any differences between the two groups.DesignCross-sectional study.SettingPrimary care clinic of a teaching hospital in NigeriaParticipants341 patients participated in the study. Of these, 60% were female and 80 % were of Hausa/Fulani ethnicity. All adult patients attending the clinic were eligible. Very sick patients were excluded from the research.Primary outcomeestimated glomerular filtration rate, microalbuminuria and proteinuria among patients who reported using herbs and those who did not report any use.Secondary outcomeelectrolyte, urea, and creatinine levels among study participants.ResultsThe mean eGFR for participants who used herbs was 87.47 ± 25.44 ml/min/1.73m2and 84.76 ± 25.49 ml/min/1.73m2for those who never used herbs (P value 0.48). Proteinuria ≥0.3g/l was present in 29(8.50%) of participants, and microalbuminuria ≥30mg/l in 138 (40.47%). There was no statistically significant difference in the renal parameters of both groups.ConclusionThe study could not establish harmful effect of the herbs reported on kidney function. Further studies in human subjects of the effect of herbal medicine on the kidney and other systems are suggested.Article SummaryStrengths and LimitationsThis study provides empiric evidence to compare renal function among users of herbal medicine and others.The study provides a detailed evaluation of renal function in the participants using estimated glomerular filtration rate, as well as urine protein and microalbumin estimation.It identifies the common herbs used in a primary care clinic in the most populous black nation.A major limitation of the study is that the quantity and frequency of herbal medicine use were not measured.
Mechanical confinement governs phenotypic plasticity in melanoma
Authors: Hunter Miranda V. , Montal Emily , Ma Yilun , Moncada Reuben , Yanai Itai , Koche Richard P. , White Richard M. 
Published: February 2024

ABSTRACTPhenotype switching is a form of cellular plasticity in which cancer cells reversibly move between two opposite extremes - proliferative versus invasive states. While it has long been hypothesised that such switching is triggered by external cues, the identity of these cues has remained elusive. Here, we demonstrate that mechanical confinement mediates phenotype switching through chromatin remodelling. Using a zebrafish model of melanoma coupled with human samples, we profiled tumor cells at the interface between the tumor and surrounding microenvironment. Morphological analysis of these rare cells showed flattened, elliptical nuclei suggestive of mechanical confinement by adjacent tissue. Spatial and single-cell transcriptomics demonstrated that the interface cells adopted a gene program of neuronal invasion, including acquisition of an acetylated tubulin cage that protects the nucleus during migration. We identified the DNA-bending protein HMGB2 as a confinement-induced mediator of the neuronal state. HMGB2 is upregulated in confined cells, and quantitative modelling revealed that confinement prolongs contact time between HMGB2 and chromatin, leading to changes in chromatin configuration that favor the neuronal phenotype. Genetic disruption of HMGB2 showed that it regulates the trade-off between proliferative and invasive states, in which confined HMGB2hightumor cells are less proliferative but more drug resistant. Our results implicate the mechanical microenvironment as a mechanism driving phenotype switching in melanoma.
Development of a LRRC15-Targeted Radio-Immunotheranostic Approach to Deplete Pro-tumorigenic Mechanisms and Immunotherapy Resistance
Authors: Storey Claire M , Altai Mohamed , Lückerath Katharina , Zedan Wahed , Zhu Henan , Trajkovic-Arsic Marija , Park Julie , Peekhaus Norbert , Siveke Jens , Lilljebjörn Henrik , Abou Diane , Marks Haley , Ulmert Enna , Lilja Hans , Ridley Alexander , Safi Marcella , Yuen Constance , Geres Susanne , Mao Liqun , Cheng Michael , Czernin Johannes , Herrmann Ken , Bentolila Laurent , Yang Xia , Fioretos Thoas , Graeber Thomas , Sjöström Kjell , Damoiseaux Robert , Thorek Daniel , Ulmert David 
Published: February 2024

ABSTRACTLeucine-rich repeat containing 15 (LRRC15) has emerged as an attractive biomarker and target for cancer therapy. We have developed a humanized monoclonal antibody (mAb), DUNP19, that specifically binds to a phylogenetically conserved LRRC15 epitope and is internalized by target-expressing cancer and stromal cells. In xenograft mouse models, Lutetium-177 labeled DUNP19 ([177Lu]-DUNP19) enables non-invasive imaging and precise radiotherapy to LRRC15-expressing cancer cells and murine cancer-associated fibroblasts (CAFs), halting tumor progression and prolonging survival with minimal toxicity. Transcriptomic analyses of [177Lu]-DUNP19-treated tumors reveal a loss of pro-tumorigenic mechanisms, including a transforming growth factor beta (TGFβ)-driven and LRRC15+ signature associated with immunotherapy resistance. Together, these results demonstrate that radio-theranostic targeting of LRRC15 with DUNP19 is a compelling precision medicine platform for image-guided diagnosis, eradication, and reprogramming of LRRC15+ tumor tissue that drives immuno-resistance and aggressive disease.SIGNIFICANCEWe introduce a pioneering LRRC15-guided radio-theranostic approach integrating clinical imaging and radioimmunotherapy. Our strategy utilizes a mAb, DUNP19, to target LRRC15-expressing cancer cells and fibroblasts, demonstrating significant tumor reduction, prolonged survival, and reversal of TGFβ-driven treatment resistance. This approach offers a promising strategy for improving outcomes in aggressive cancers.
CELL CYCLE STATE PREDICTION USING GRAPH NEURAL NETWORKS
Authors: Acharya Sayan , Ganguly Aditya , Sarkar Ram , Jose Abin 
Published: February 2024

ABSTRACTMitosis is a crucial process ensuring the faithful transmission of the genetic information stored in the cell nucleus. Aberrations in this intricate process pose a significant threat to an organism’s health, leading to conditions like cancer and various diseases. Hence, the study of mitosis holds paramount importance. Recent investigations have involved manual and semiautomated analyses of time-lapse microscopy images to understand mitosis better. This paper introduces an approach for predicting mitosis stages, employing a Convolutional Neural Network (CNN) as the initial feature extractor, followed by a Graph Neural Network (GNN) for predicting cell cycle states. A distinctive timestamp is incorporated into the feature vectors, treating this information as a graph to leverage internal interactions for predicting the subsequent cell state. To assess performance, experiments were conducted on three datasets, demonstrating that our method exhibits comparable efficacy to state-of-the-art techniques.
Integrated Closed-loop Control of Bio-actuation for Proprioceptive Bio-hybrid Robots
Authors: Filippi Miriam , Balciunaite Aiste , Georgopoulou Antonia , Paniagua Pablo , Drescher Felix , Nie Minghao , Takeuchi Shoji , Clemens Frank , Katzschmann Robert 
Published: February 2024

AbstractBiohybrid robots are emergent soft robots that combine engineered artificial structures and living biosystems to exploit unique characteristics of biological cells and tissues. Skeletal muscle tissue-based bio-actuators can respond to externally applied stimuli, such as electrical fields. However, current bio-actuation systems rely on open-loop control strategies that lack knowledge of the actuator’s state. The regulation of output force and position of bio-hybrid robots requires self-sensing control systems that combine bio-actuators with sensors and control paradigms. Here, we propose a soft, fiber-shaped mechanical sensor based on a composite with piezoresistive properties that efficiently integrates with engineered skeletal muscle tissue and senses its contracting states in a cell culture environment in the presence of applied electrical fields. After testing the sensor’s insulation and biocompatibility, we characterized its sensitivity for typical strains (<1%) and proved its ability to detect motions from contractile skeletal muscle tissue constructs. Finally, we showed that the sensor response can feed an autonomous control system, thus demonstrating the first proprioceptive bio-hybrid robot that can sense and respond to its contraction state. In addition to inspiring intelligent implantable systems, informative biomedical models, and other bioelectronic systems, the proposed technology will encourage strategies to exceed the durability, design, and portability limitations of biohybrid robots and confer them decisional autonomy, thus driving the paradigm shift between bio-actuators and intelligent bio-hybrid robots.One Sentence SummaryIntegrating soft mechanical sensors into engineered skeletal muscle tissue enables bio-hybrid robots with proprioception.
miR-210 is essential to retinal homeostasis in fruit flies and mice
Authors: Colaianni Davide , Virga Federico , Tisi Annamaria , Stefanelli Chiara , Zaccagnini Germana , Cusumano Paola , Sales Gabriele , Ivan Mircea , Martelli Fabio , Taverna Daniela , Mazzone Massimiliano , Bertolucci Cristiano , Maccarone Rita , De Pittà Cristiano 
Published: February 2024

SummarymiR-210 is one of the most evolutionarily conserved microRNAs. Recent studies inDrosophila melanogasterhave unveiled that the absence of miR-210 leads to a progressive retinal degeneration characterized by the accumulation of lipid droplets and disruptions in lipid metabolism. Further investigation into lipid anabolism and catabolism revealed significant alterations in gene expression within these pathways. We provide the first morphological characterization of miR-210 KO mice retinas, highlighting a significant photoreceptor degeneration. While exploring potential parallels between miR-210 KO models in flies and mice, we examined mice lipid metabolism, circadian behaviour, and retinal transcriptome yet found no resemblances, suggesting divergent mechanisms of retinal degeneration between the two species. Simultaneously, analysis of the transcriptome in the brains of miR-210 KO flies revealed the potential existence of a shared upstream mechanism contributing to retinal degeneration in both fruit flies and mammals.
A mutant ASXL1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia
Authors: Dong Zhen , Sepulveda Hugo , Arteaga-Vazquez Leo J. , Blouin Chad , Fernandez Jenna , Binder Moritz , Chou Wen-Chien , Tien Hwei-Fang , Patnaik Mrinal , Faulkner Geoffrey J , Myers Samuel A , Rao Anjana 
Published: February 2024

AbstractASXL1is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongsideDNMT3AandTET2. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML), and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing de-repression of silenced elements in heterochromatin. In contrast, the mechanisms that connect mutant ASXL1 and CH are not yet fully understood. CH/CMML-associatedASXL1mutations encode C-terminally truncated proteins that enhance the deubiquitinase activity of the ASXL-BAP1 “PR-DUB” deubiquitinase complex, which removes mono-ubiquitin from H2AK119Ub. Here we show that ASXL1 mutant proteins interact with the EHMT1-EHMT2 methyltransferase complex, which generates H3K9me1 and me2, the latter a repressive modification in constitutive heterochromatin. Compared to cells from age-matched wildtype mice, we found that expanded myeloid cells from old (≥18-month-old)Asxl1tm/+mice, a heterozygous knock-in mouse model of CH, display genome-wide decreases of H3K9me2, H3K9me3 and H2AK119Ub as well as an associated increase in expression of transposable elements (TEs) and satellite repeats. Increased TE expression was also observed in monocytes fromASXL1-mutant CMML patients compared to monocytes from healthy controls. Our data suggest that mutant ASXL1 proteins compromise the integrity of both constitutive and facultative heterochromatin in an age-dependent manner, by reducing the levels of H3K9me2/3 and H2AK119Ub. This increase in TE expression correlated with increased expression of nearby genes, including many interferon-inducible (inflammation-associated) genes (ISGs).Significance StatementAge-related clonal hematopoiesis (CH) is a premalignant condition associated with inflammatory cardiovascular disease.ASXL1mutations are very frequent in CH. We show that ASXL1 interacts with EHMT1 and EHMT2, H3K9 methyltransferases that deposit H3K9me1 and me2. Using a mouse model of mutantASXL1to recapitulate CH, we found that old ASXL1-mutant mice showed marked expansion of myeloid cells in bone marrow, with decreased H3K9me2/3 and increased expression of transposable elements (TEs) in heterochromatin. In humans, ASXL1-mutant CH progresses to chronic monomyelocytic leukemia (CMML); CMML patient samples showed striking upregulation of many TE families, suggesting that ASXL1 mutations compromise heterochromatin integrity, hence causing derepression of TEs. Targeting heterochromatin-associated proteins and TEs might counter the progression of CH, CMML and other myeloid malignancies.
Identifying compositional and density changes across the Murine and Human Dentin-enamel Junction
Authors: Truhlar Michael , Rosenberg Bradley , Katebifar Sobhan , Kroger Roland , Deymier Alix 
Published: February 2024

AbstractHuman and mouse incisors are both primarily composed of dentin and enamel which meet at an interface called the dentin-enamel junction (DEJ). However, incisors in the two species have very different growth patterns, structures, and loading requirements. Since the DEJ is responsible for minimizing cracking at this at-risk interface between mechanically dissimilar dentin and enamel, its structure is expected to be significantly different between humans and mice. Here, strucutral and compositional gradients across human and murine incisors DEJs were measured via microcomputed tomography and Raman spectroscopy. Density gradients across the DEJ were significantly larger in humans compared to murine teeth likely due to the larger size of the mantle dentin. Multiple gradients in mineral content and crystallinity were found at the murine DEJ while the human DEJ only exhibited gradients in mineral content. Models predicting the modulus across the DEJ according to compositional results show that mineral crystallinity is critical in regulating the mechanical gradient across the murine DEJ. Together these results show the multiple ways in which the DEJ can adapt to variations in loading environment.
Single-Cell Peripheral Immunoprofiling of Lewy Body Disease in a Multi-site Cohort
Authors: Phongpreecha Thanaphong , Mathi Kavita , Cholerton Brenna , Fox Eddie J. , Sigal Natalia , Espinosa Camilo , Reincke Momsen , Chung Philip , Hwang Ling-Jen , Gajera Chandresh R. , Berson Eloise , Perna Amalia , Xie Feng , Shu Chi-Hung , Hazra Debapriya , Channappa Divya , Dunn Jeffrey E. , Kipp Lucas B. , Poston Kathleen L. , Montine Kathleen S. , Maecker Holden T. , Aghaeepour Nima , Montine Thomas J. 
Published: February 2024

SummaryStudies implicated peripheral organs involvement in the development of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson’s Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). This study characterized peripheral immune responses unique to LBD at single-cell resolution. Peripheral mononuclear cell (PBMC) samples were collected from sites across the U.S. The diagnosis groups comprise healthy controls (HC, n=164), LBD (n=132), Alzheimer’s disease dementia (ADD, n=98), other neurodegenerative disease controls (NDC, n=21), and immune disease controls (IDC, n=14). PBMCs were activated with three stimulants, stained by surface and intracellular signal markers, and analyzed by flow cytometry, generating 1,184 immune features. Our model classified LBD from HC with an AUROC of 0.90±0.06. The same model distinguished LBD from ADD, NDC, IDC, or other common conditions associated with LBD. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations and activations.