bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of MLF1 safeguards cardiomyocytes against senescence-associated chromatin opening
Authors: Lv Jian , Chen Qin , Wang Junmei , Guo Ningning , Fang Yu , Guo Qiuxiao , Li Jiajie , Ma Xiao , Zhan Hongchao , Chen Weihao , Wang Li , Yan Qingqing , Tong Jingjing , Wang Zhihua
Published: December 2024

Aging-associated cardiac hypertrophy (AACH) increases susceptibility to heart failure in the elderly. Chromatin remodeling contributes to the gene reprogramming in AACH; however, the intrinsic regulations remain elusive. We performed a transcriptome analysis for AACH in comparison with pressure-overload-induced pathological cardiac hypertrophy in mice and identified myeloid leukemia factor 1 (MLF1) as an aging-sensitive factor whose expression was reduced during aging but could be reversed by anti-aging administrations. In human AC16 cardiomyocytes, silencing MLF1 suppressed H2O2-induced cell senescence while the phenotype was exacerbated by MLF1 overexpression. RNA-seq analysis revealed that MLF1 functioned as a transcription activator, regulating genomic-clustered genes that mainly involved in inflammation and development. ATAC-seq analysis showed a prominent reduction in chromatin accessibility at the promoter regions of senescence effectors, like IL1B and p21, after MLF1 knockdown. Despite a potential interaction of MLF1 with the histone methyltransferase PRC2, its inhibition failed to reverse the impact of MLF1 knockdown. Instead, MLF1-mediated regulation was blunted by inhibiting the acetyltransferase EP300. CUT&Tag analysis showed that MLF1 bound to target promoters and recruited EP300 to promote H3K27ac deposition. Collectively, we identify MLF1 as a pro-aging epigenetic orchestrator that recruits EP300 to facilitate opening of the condensed chromatin encompassing senescence effectors.
Using paired-end read orientations to assess technical biases in capture Hi-C
Authors: Hansen Peter , Blau Hannah , Hecht Jochen , Karlebach Guy , Krannich Alexander , Steinhaus Robin , Truss Matthias , Robinson Peter N
Published: December 2024

Hi-C and capture Hi-C (CHi-C) both leverage paired-end sequencing of chimeric fragments to gauge the strength of interactions based on the total number of paired-end reads mapped to a common pair of restriction fragments. Mapped paired-end reads can have four relative orientations, depending on the genomic positions and strands of the two reads. We assigned one paired-end read orientation to each of the four possible re-ligations that can occur between two given restriction fragments. In a large hematopoietic cell dataset, we determined the read pair counts of interactions separately for each orientation. Interactions with imbalances in the counts occur much more often than expected by chance for both Hi-C and CHi-C. Based on such imbalances, we identified target restriction fragments enriched at only one instead of both ends. By matching them to the baits used for the experiments, we confirmed our assignment of paired-end read orientations and gained insights that can inform bait design. An analysis of unbaited fragments shows that, beyond bait effects, other known types of technical biases are reflected in count imbalances. Taking advantage of distance-dependent contact frequencies, we assessed the impact of such biases. Our results have the potential to improve the design and interpretation of CHi-C experiments.
TGV: suite of tools to visualize transmission graphs
Authors: Phelan Jody E , Niazi Fatima , Wang Linfeng , Ngwana-Joseph Gabrielle C , Sobkowiak Benjamin , Cohen Ted , Campino Susana , Clark Taane G
Published: December 2024

Graph structures are often used to visualize transmission networks generated using genomic epidemiological methods. However, tools to interactively visualize these graphs do not exist. A browser-based tool allowing users to load and interactively visualize transmission graphs was developed in JavaScript. Associated metadata can be loaded and used to annotate and filter the nodes and edges of transmission networks. The tool is available at jodyphelan.github.io/tgv.
Artificial Sweeteners in US-Marketed Oral Nicotine Pouch Products: Correlation With Nicotine Contents and Effects on Product Preference
Authors: Jabba Sairam V , Silinski Peter , Yang Alicia Y , Ouyang Wenyi , Jordt Sven E
Published: December 2024

Introduction

Artificial sweeteners, sucralose and acesulfame-k, are listed as ingredients of oral nicotine pouches (ONPs), a product category with a rapidly growing market share. The exact quantities of these sweeteners in ONPs remain unknown. Artificial sweeteners in ONPs may reduce aversion, facilitate initiation, and encourage consumption behavior.

Aims and Methods

Sucralose and acesulfame-k contents in major US-marketed ONP brands (Zyn, on!, and Velo) were determined by liquid chromatography–mass spectrometry. Sweetener effects on aversion and consumption of ONPs were modeled in single- and two-bottle drinking tests, offering mice ONP extracts calibrated to contain nicotine levels similar to the saliva of people who use smokeless tobacco. To examine the contribution of sweet taste perception, consumption behavior was compared between wild-type and sweet taste receptor-deficient mice (Tas1r2−/−).

Results

Acesulfame-k was detected in on!, Zyn, and Velo ONPs (~0.3 to 0.9 mg/pouch), including products marketed as “Unflavored” or “Flavor ban-approved.” In Velo ONPs, sweetened with sucralose (~0.6 to 1.2 mg/pouch), higher nicotine strength products contained higher sucralose levels. Tas1r2−/− mice consumed less ONP extracts than wild-type mice in both sexes. ONP extracts with both higher nicotine and sweetener strengths were tolerated by wild-type mice, but produced stronger aversion in Tas1r2−/− mice.

Conclusions

ONPs contain significant amounts of artificial sweeteners acesulfame-k and sucralose, with some brands adding more sweeteners to higher nicotine strength ONPs. In mice, artificial sweeteners, at levels present in ONPs, increase nicotine consumption. Increasing sweetener contents facilitates the consumption of higher nicotine strength ONPs. Sweetness imparted by sweetener addition to ONPs likely reduces the aversive sensory effects of nicotine and other ONP constituents.

Implications

Artificial sweeteners such as acesulfame-k or sucralose reduce aversion and likely facilitate the consumption of ONPs. The marketing of some artificially sweetened ONPs as “Unflavored” or “Flavor ban-approved” suggests that the tobacco industry rejects sweet taste as a determinant for the presence of a characterizing flavor. Sweetness as imparted by artificial sweeteners in tobacco products needs to be addressed by regulators as a component of a characterizing flavor, with the aim to reduce product appeal and initiation by never users, and especially youth attracted to sweet flavors.
On learning what to learn: Heterogeneous observations of dynamics and establishing possibly causal relations among them
Authors: Sroczynski David W , Dietrich Felix , Koronaki Eleni D , Talmon Ronen , Coifman Ronald R , Bollt Erik , Kevrekidis Ioannis G
Published: December 2024

Before we attempt to (approximately) learn a function between two sets of observables of a physical process, we must first decide what the inputs and outputs of the desired function are going to be. Here we demonstrate two distinct, data-driven ways of first deciding “the right quantities” to relate through such a function, and then proceeding to learn it. This is accomplished by first processing simultaneous heterogeneous data streams (ensembles of time series) from observations of a physical system: records of multiple observation processes of the system. We determine (i) what subsets of observables are common between the observation processes (and therefore observable from each other, relatable through a function); and (ii) what information is unrelated to these common observables, therefore particular to each observation process, and not contributing to the desired function. Any data-driven technique can subsequently be used to learn the input–output relation—from k-nearest neighbors and Geometric Harmonics to Gaussian Processes and Neural Networks. Two particular “twists” of the approach are discussed. The first has to do with the identifiability of particular quantities of interest from the measurements. We now construct mappings from a single set of observations from one process to entire level sets of measurements of the second process, consistent with this single set. The second attempts to relate our framework to a form of causality: if one of the observation processes measures “now,” while the second observation process measures “in the future,” the function to be learned among what is common across observation processes constitutes a dynamical model for the system evolution.
Perceptual categorization and perceptual concepts
Authors: Green E J
Published: December 2024

Conceptualism is the view that at least some perceptual representation is conceptual. This paper considers a prominent recent argument against Conceptualism due to Ned Block. Block's argument appeals to patterns of color representation in infants, alleging that infants exhibit categorical perception of color while failing to deploy concepts of color categories. Accordingly, the perceptual representation of color categories in infancy must be non-conceptual. This argument is distinctive insofar as it threatens not only the view that all perception is conceptual, but also views that restrict the Conceptualist thesis to perceptual categorization. However, I contend that it fails at two stages. Block's arguments for the perceptual representation of color categories in infancy, and against color concept deployment in infancy, are unpersuasive. Thus, Block has not vanquished Conceptualism. I draw out implications for debates about the perception–cognition border and for the question of whether explicit categorization occurs in perception.
Extension of Λ NN → NNN Weak Interactions and the Two-Nucleon Induced Hypernuclear Nonmesonic Decays: Roles of Strange-Meson and Δ 33-Induced (ρρ)-Pair Exchanges
Authors: Itonaga K , Motoba T , Rijken Th A
Published: December 2024

In the preceding paper we introduced three-body $\Lambda NN \rightarrow NNN$ weak interactions and proposed a framework to deduce the effective two-body $\Lambda N \rightarrow NN$ potentials to be used for estimates of nonmesonic decay rates of hypernuclei. In order to complete the framework, here we extend the treatment to include new diagrams arising from strange-meson exchanges and the $\Delta _{33}$-isobar induced $(\rho \rho )$-pair exchange. Thus we present new forms of the $V^{(\text {eff.2B})}_{(K \pi )\kappa }$, $V^{(\text {eff.2B)}}_{(K \pi )K^{*}}$, and $V^{(\text {eff.2B})}_{D33(\rho \rho )}$ potentials. By adding these potentials to the previous ones, we investigate in full the roles of various types of effective $\Lambda N \rightarrow NN$ potentials in the estimates of two-nucleon induced nonmesonic decays. It is shown that the destructive interference of the tensor forces between the strange-meson-exchange potentials and the non-strange-meson-exchange ones is particularly important in reducing the theoretical two-nucleon induced nonmesonic decay rates. The potential $V^{(\text {eff.2B})}_{D33(\rho \rho )}$ is weak in comparison with $V^{(\text {eff.2B})}_{\rm FM(\pi \pi )}$. The full terms of the potentials have features of strong central, moderately strong, or weak tensors, and weak parity-violating vector forces. Erroneous overestimates of the decay rates reported in the previous paper are corrected, and new numbers calculated with the full terms are presented for the two-nucleon induced decay rates of the $^5_\Lambda {\rm He}$, $^{11}_\Lambda {\rm B}$, and $^{12}_\Lambda {\rm C}$ hypernuclei, which are comparable to the experimental data.
Evaluation of yeast-based additives on rumen fermentation in high- and low-concentrate diets using a dual-flow continuous culture system
Authors: Cagliari Amanda Regina , Magnani Elaine , Loregian Kalista Eloisa , Rigon Fernanda , Casagrande Ana Claudia , Amancio Bruna Roberta , Giacomelli Charles Marcon , da Silva Juliana Bueno , Santos Veronica Lisboa , Marcondes Marcos Inacio , Branco Renata Helena , Del Bianco Benedeti Pedro , Paula Eduardo Marostegan de
Published: December 2024

The objective of this study was to evaluate the efficacy of using 3 yeast-based additives as an alternative to sodium monensin on rumen fermentation parameters using a dual-flow continuous fermentation system. Ten fermenters (1,223 ± 21 mL) were used in 2 simultaneous 5 × 5 Latin squares arrangement with 3 periods of 10 d each, with 7 d for diet adaptation and 3 d for sample collections. Each Latin square assigning either a low or high level of concentrate to beef cattle diets, with 5 specified treatments: Control: no additives; Blend 1: yeast culture (Saccharomyces cerevisiae), beta-glucans, fructooligosaccharides, galactooligosaccharides, and mannanoligosaccharides [1,600 mg/kg dry matter (DM)]; Blend 2: Beta-glucan and mannanoligosaccharide fractions from S. cerevisiae (1,600 mg/kg DM); Yeast Cells: hydrolyzed, inactivated, and spray-dried yeast cells (S. cerevisiae; 2,133 mg/kg DM); monensin (25 mg/kg DM). On days 8, 9, and 10, samples of 500 mL of solid and liquid digesta effluent were mixed, homogenized, and stored at −20 °C. Subsamples of 10 mL were collected for later determination of ammonia nitrogen (NH3–N) and volatile fatty acids (VFA). Diets with high-concentrate showed higher organic matter (OM) digestibility but lower crude protein and neutral detergent fiber (NDF) digestibilities (P < 0.01). There were no feed additive effects for DM, OM, and NDF digestibilities (P > 0.05). Total VFA concentration and butyrate concentration were higher for the high-concentrate diet (P < 0.01). Conversely, pH and concentrations of acetate and iso-butyrate were higher for the low-concentrate diet (P < 0.01). Treatments with Blend 1, Blend 2, and Yeast Cells had higher VFA concentrations compared to the control (P = 0.04). Blend 1 treatment exhibited higher propionate concentration in fermenters fed with a high-concentrate diet (P < 0.01). In the high-concentrate diet, Blend 1 had a lower acetate: propionate ratio compared to Control, Yeast Cells, and Blend 2 treatments (P < 0.01). The high-concentrate diet showed higher means for all other parameters: Microbial efficiency, N efficiency, N flow, and Bacterial N flow (P < 0.01). Treatments with Blend 2 and Control showed higher rumen undegradable protein N flow compared to Yeast Cells and Blend 1 treatments (P < 0.01). Our findings imply that yeast-based additives might be used as alternatives to monensin, improving ruminal fermentation and promoting enhanced sustainability in livestock.
Snaplage residue as a fiber source for finishing beef cattle under grazing: effects on residue characteristics, cattle behavior and performance, and carcass traits
Authors: de Lima Italo B G , Cruz Priscila J R , Borges Lucas P C , Gionbelli Mateus P , Ladeira Marcio M , Shike Daniel W , Casagrande Daniel R , Bernardes Thiago F
Published: December 2024

The snaplage residue presents itself as a potential alternative roughage source in finishing systems, owing to its high fiber concentration which aids in maintaining rumen health. Nevertheless, the performance of animals will hinge on both the allowance and the nutritive value it offers. This study aimed to evaluate different stocking rates of heifers grazing snaplage residue as an exclusive source of fiber on finishing phase performance. The treatments included two stocking rates (SR): i) low stocking rate (LS; 3.5 AU/ha) and ii) high stocking rate (HS; 7.0 AU/ha), which were obtained by modifying the size of the paddocks. Crossbred beef heifers (n = 48; initial body weight = 276 ± 23 kg) were assigned to 16 paddocks (3 heifers/paddock). The concentrate (87% of corn, 3.5% of soybean meal, 3.9% of cottonseed meal, 1.2% of urea, and 4% of mineral; DM basis) was fed ad libitum daily at 0600 hours. Data were analyzed using the MIXED procedure of SAS. There was no SR × time effect (P = 0.88) on residue mass. There was less (P < 0.01) total residue mass for HS than LS, and total mass decreased (P < 0.01) over time. There was no SR × time effect (P ≥ 0.16) for behavior characteristics. There was no difference between HS and LS for average residue intake (P = 0.34; 0.44 vs 0.48 kg/d, respectively), concentrate intake (P = 0.84; 7.72 vs 7.78 kg/d, respectively), and daily gain (ADG; P = 0.94; 0.95 vs 0.95 kg/d, respectively), The HS treatment increased (P < 0.01) gain per area (618 vs 309 kg/ha) compared to LS. No differences between SR were observed for carcass characteristics (P ≥ 0.12). The meat’s chemical composition was not different (P ≥ 0.37) between treatments. Overall, the snaplage residue stocking rate did not affect the finishing phase performance of beef heifers, but the greater stocking rate (7.0 AU/ha) increased gain per land area.
Sex-Specific Obesity Paradox in Critically Ill Patients With Severe Acute Kidney Injury: A Retrospective Analysis
Authors: Jung Hyo Jin , Seo Yu Jin , Jung Jiyun , Lee Jangwook , Park Jae Yoon , Kim Yong Chul , Lee Sung Woo , Ban Tae Hyun , Park Woo Yeong , Kim Kipyo , Kim Hyosang , Kim Kyeongmin , Jung Hee-Yeon , Choi Ji-Young , Cho Jang-Hee , Park Sun-Hee , Kim Chan-Duck , Lim Jeong-Hoon , Kim Yong-Lim
Published: December 2024

OBJECTIVES:

Although obesity is typically correlated with adverse outcomes in various diseases, certain acute critical illnesses exhibit a phenomenon known as the obesity paradox. This study evaluated sex-specific differences in the prognostic implications of the body mass index (BMI) of patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT).

DESIGN:

A multicenter retrospective cohort study.

SETTING:

Data from eight tertiary hospitals in Korea.

PATIENTS:

A total of 3805 critically ill patients receiving CRRT. Patients were categorized into four BMI groups: underweight, normal weight, overweight, and obese.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

There were 2308 male and 1497 female patients. The 90-day mortality risk significantly differed among BMI groups in the overall patient population and the male subpopulation but not the female subpopulation. Following adjustment for confounding variables, the 90-day mortality risk was higher in the underweight group than in the obese group (hazard ratio [HR], 1.20; 95% CI, 1.05–1.36; p = 0.006). Among male patients, the 90-day mortality risk was higher in both the underweight and normal weight groups than in the obese group (underweight: HR, 1.30; 95% CI, 1.10–1.53; p = 0.002 and normal weight: HR, 1.18; 95% CI, 1.04–1.35; p = 0.010); however, no such association was observed among female patients. Subgroup analysis demonstrated the obesity paradox in male patients of old age, with septic AKI, or with low albumin levels.

CONCLUSIONS:

There were sex differences in the association between BMI and mortality in critically ill patients with severe AKI. Although the precise distribution of fat mass and muscle mass was not identified, obese male patients had a more favorable prognosis, which was not evident among female patients. These findings highlight the importance of considering sex-specific factors in understanding the complex relationship between obesity and mortality in critically ill patients with AKI.
Evolution of Diagnostic Medical Physics Enterprise
Authors: Misseldine Ryan , Kocak Ryan , Dietz Andrew , Leuenberger Ronald , Jordan David
Published: December 2024

The roles and responsibilities of radiation safety officers (RSO), medical health physicists (MHP) and diagnostic medical physicists (DMP) have evolved significantly over the past 20 years. With the availability of enterprise software systems and aggregated data platforms for various radiologic healthcare systems, the roles of these professions are expanding beyond their original scopes in managing the Radioactive Materials License (RSO, MHP) and Machine Specific Physics Testing (DMP). Workers in medical radiation safety are transitioning from siloed workers working within their specific disciplines as new emerging technology and clinical care require these roles to evolve. This paper aims to demonstrate the value in embracing the change in these roles to better serve the patients and occupational workers RSOs, MHPs, and DMPs serve. As medical physics enterprise solutions evolve, so will the relationships between these valuable stakeholders.
Long-term Follow Up of a Complex Case of Foldable Capsular Vitreous Bag Implantation
Authors: Christou Louise , Coupland Sarah E , Hunter Guy , Hussain Rumana
Published: December 2024

Purpose:

The Foldable Capsular Vitreous Bag (FCVB) implant is useful in maintaining ocular structure in cases of chronic hypotony secondary to trauma or repeated surgery. There are few published reports of long-term outcomes and no indication of the chronic cellular changes of the adjacent tissues associated with FCVB implantation. We describe one of few FCVB cases in the UK and present histological findings associated with it following secondary enucleation.

Methods:

A 33-year-old man underwent a left primary globe repair following a left penetrating injury and intraocular metal foreign body secondary to a close-range blast injury. Postoperatively, a retinal detachment was detected and a left vitrectomy with lensectomy, retinectomy and silicone oil (SO) insertion was performed. Subsequently, pupillary prolene sutures were used to create a two-chamber eye. Despite this, hypotony, SO in the anterior chamber and upper limb deep vein thromboses (DVTs) occurred postoperatively. He had a complex history of Factor V Leiden with renal thrombosis in childhood. After warfarinisation, his FCVB procedure was uneventful with a good bag SO fill.

Results:

Post-operative outcomes were initially favourable; however, enucleation was necessary almost three years post-implantation due to spontaneous left hyphaema and intractable raised intraocular pressure. Histology revealed extensive intraretinal fibrotic pannus membranes, loss of photoreceptor architecture and focal foreign body-cell reaction.

Conclusions:

A complex case of FCVB implantation following ocular trauma with post-operative complications years later. Long-term outcomes of FCVBs are poorly understood; this case was complicated by the patient’s systemic coagulopathy.
Mediating Role of Financial Toxicity in the Relationships Between Health-Related Quality of Life and Its Risk Factors in Chinese Patients With Cancer
Authors: Xu Binbin , So Winnie K. W. , Choi Kai Chow , Huang Yu , Liu Mei , Qiu Lanxiang , Tan Jianghong , Tao Hua , Yan Keli , Yang Fei
Published: December 2024

Background

Factors influencing health-related quality of life (HRQoL) and financial toxicity (FT) have been found to overlap, and the robust correlation between HRQoL and FT raises the possibility that FT mediates the relationships between the shared risk factors and HRQoL. However, empirical evidence supporting this hypothesis is limited.

Objective

This study aimed to explore whether FT mediates the relationships between HRQoL and its risk factors.

Methods

A cross-sectional study was conducted, with 1208 participants from 12 hospitals (6 tertiary, 6 secondary) in 6 cities across 3 income-level-diverse provinces in China from February to October 2022. FT and HRQoL were measured using the COmprehensive Score for financial Toxicity and the Functional Assessment of Cancer Therapy—General. Twenty-two risk factors for both HRQoL and FT were included for analysis. Mediation analyses were conducted using Mplus 8.3.

Results

FT predominantly mediated the relationships between HRQoL and both annual household income and hospital level. Meanwhile, it partially mediated the relationships of HRQoL with the number of treatment modalities, social support, perceived stress, healthcare provider–patient discussion regarding cancer care costs, and social medical insurance, and the mediating effect accounted for 19.7%, 7.8%, 10.7%, 22.3%, and 46.8% of the total effect, respectively.

Conclusions

FT plays a significant mediating role in the associations between HRQoL and some of its risk factors among patients with cancer.

Implications for Practice

Developing a more comprehensive and patient-centered approach to cancer care that addresses the unique challenges posed by cancer-related FT is urgently needed to improve the HRQoL among this population.
AONL Foundation–Funded Studies Offer Insights on Resilience, Recognition, and Chief Nurse Executive Turnover
Authors: Ward Danielle M.
Published: December 2024

Since the American Organization for Nursing Leadership (AONL) Foundation for Nursing Leadership Research and Education began awarding grants for nursing leadership research in 2003, more than $500,000 has funded research supporting nurse leaders of all levels. This column discusses several studies that leaders of all levels, but most especially the senior leaders, chief nurse executives, and others, may find useful. Publications from these studies are ongoing, and readers will be able to access links to published articles on the AONL Foundation's website.
Claudin-18 and Mutation Surrogate Immunohistochemistry in Gastric-type Endocervical Lesions and their Differential Diagnoses
Authors: Lin Lawrence Hsu , Kaur Harsimar , Kolin David L. , Nucci Marisa R. , Parra-Herran Carlos
Published: December 2024

Gastric-type endocervical adenocarcinomas (GAS) are aggressive HPV-independent neoplasms with molecular alterations in TP53, STK11, CDKN2A, and SMAD4. Claudin-18 (CLDN18) has emerged as a useful marker to distinguish GAS from HPV-associated neoplasia. Its role in separating GAS from benign proliferations and exuberant endocervical glands is unknown. We studied the utility of immunohistochemistry for CLDN18, progesterone receptor (PR), and mutation surrogate stains (P53, STK11/LKB1, MTAP, SMAD4/DPC4) in 46 GAS, 12 benign gastric-type endocervical lesions, 54 benign Mullerian endocervical populations, and 11 HPV-associated endocervical adenocarcinomas. PD-L1 and HER2 immunostains were evaluated in GAS. Gastric-type lesions were more often positive for CLDN18 (100% benign, 78% GAS, most often well to moderately differentiated) compared to benign Mullerian endocervical specimens (all negative) and HPV-associated neoplasia (18%, always focal). Conversely, PR was negative in all gastric-type lesions and positive in 92% of benign Mullerian endocervical populations. GAS revealed aberrant/mutant expression of P53 in 35%, STK11/LKB1 in 25%, MTAP in 23%, and SMAD4/DPC4 in 9% of cases. Abnormal staining in at least one of these 4 mutation surrogate markers was present in 63% of GAS. HER2 score of 3+ was seen in 25% of GAS, and PD-L1 was positive in 37% based on a combined positive score. CLDN18 is a sensitive and highly specific marker of gastric-type benign and malignant endocervical lesions. Once a gastric-type phenotype is confirmed, mutation surrogate immunostains can be used to support a diagnosis of GAS. PD-L1 and HER2 expression is seen in a subset of GAS offering therapeutic options for this aggressive tumor.
Supporting physical activity for health: What activities would people with transtibial amputation like to perform?
Authors: Asher Miranda , Diss Ceri , Strike Siobhan
Published: December 2024

Background:

Participation in physical activity (PA) for health by people with transtibial amputation (PTTA) may moderate comorbidities experienced by this population. It is more likely that interventions which aim to increase participation by PTTA in PA for health will increase participation if the type of PA used is tailored to the preferences of the PTTA.

Objective:

This study aimed to identify the types of PA performed by PTTA, the types of PA PTTA who performed no physical activities would like to adopt, and if these outcomes were influenced by the cause of amputation.

Methods:

The cross-sectional survey was accessible through an online survey tool and in paper format. It was distributed primarily at sports events and relevant locations, which support people with limb differences. A total of 115 PTTA adults (both active and those who did not perform any physical activities) completed the survey, consisting of 65 people with amputation due to traumatic causes and 50 people with amputation due to nontraumatic causes.

Results:

From all PTTA respondents, the most popular current activities were walking (N = 42), going to the gym (N = 39), swimming (N = 35), and cycling (N = 32). For PTTA who did not perform any physical activity, the most popular PA they would like to participate in were walking (N = 10), going to the gym (N = 8), swimming (N = 7), and cycling (N = 6). While there are differences in the hierarchy of popularity of different types of PA depending on the cause of amputation, these results indicate some consistencies.

Conclusions:

Walking, going to the gym, swimming, and cycling appear throughout the results, indicating a potential to encourage PTTA participation in PA for health through these activities.
The Fate of the Frozen Bone Flap: Quantitative and Volumetric Assessment Following Cranioplasty Using the Autologous Bone Flap
Authors: Cherukuri Sai K. , Van Gompel Jamie , Zheng Eugene E. , Vierkant Robert A. , Meira Pazelli Alexandre , Mardini Samir , Morris Jonathan , Sears Victoria A. , Gibreel Waleed
Published: December 2024

Objective:

The pattern, rate, and natural history of bone flap resorption following cranioplasty with frozen, autologous bone flap has not been fully defined. The authors sought to quantify the progression and natural history of bone flap resorption.

Methods:

Patients who had craniectomy and delayed cranioplasty with stored, frozen bone flap between 2012 and 2022 were included in this study.

Results:

Ninety patients (63% male) were included, with a median age of 44.8 years (range: 4.2–84.4 y) at the time of autologous bone flap cranioplasty. Delayed, autologous cranioplasty occurred at a median time of 29.5 days (range: 2 d–10 y) from the index craniectomy. The median follow-up was 16.6 months (range: 3.4–85.4 mo). Radiographically quantifiable bone flap resorption occurred in 50 patients (56%). During the follow-up, the average percentage volume loss was 17%, with a nonlinear pattern of resorption. Following delayed, autologous cranioplasty, 11 patients had clinically significant bone flap resorption requiring secondary alloplastic cranioplasty at a median time of 13.8 months (range: 5.9–57.2 mo), with a mean percentage volume loss of 61%. Younger age was a risk factor for bone flap resorption (P < 0.05), whereas active smoking, presence of comorbidities, and number of days of bone flap storage were not risk factors for bone flap resorption. Penalized B-spline regression analysis showed that bone flap resorption followed a nonlinear pattern.

Conclusion:

Radiographically quantifiable bone flap resorption occurred in about 56% of patients following delayed autologous cranioplasty. Resorption followed a non-linear pattern. Young age is a risk factor for bone flap resorption.
Isolation and molecular characterization of foot-and-mouth disease viruses from small ruminants in Nigeria.
Authors: Ehizibolo David , Oyekan Olumuyiwa , Oguche Moses , Ardo Abdullahi , Ludi Anna , Wood Britta , Gubbins Simon , Hicks Hayley , Wadsworth Jemma , Chevanne Etienne , Rosso Fabrizio , Knowles Nick , Mioulet Valerie , King Donald , Limon Georgina
Published: December 2024

Foot-and-mouth disease (FMD) poses significant economic challenges to the livestock industry in Nigeria due to its widespread prevalence and detrimental impacts on animal health and international trade. Documented FMD outbreaks in the endemic areas of West and Central Africa consistently highlight the role of cattle as the indicator species for FMD. However, the role of small ruminants (SR) is poorly understood. Aiming to improve our understanding of the role of SR in the epidemiology of the disease, this study investigated FMD outbreaks on farms where cattle intermixed with sheep and goats. Blood and oral swabs (n=177) were collected from 138 sheep and 39 goats in nine local government areas (LGAs) of Plateau State, Nigeria. Additionally, epithelial tissue samples were obtained from suspected cases of FMD in six sheep and three goats in four of the LGAs. The majority (71.2%, 95% CI 64-77) of SR sampled seroconverted to FMDV measured by a 3ABC non-structural protein (NSP) enzyme-linked immunosorbent assay (ELISA) where 77.5% (95% CI 70.7-84.5) of sheep and 48.7% (95% CI 33-64.4) goats tested positive for FMDV-NSP antibodies. FMDV genomic RNA was detected in 36.6% (95% CI 25-49) of oral swabs samples collected from SR and two FMDV serotypes: O and A were detected using antigen-ELISA. Phylogenetic analyses of the VP1 coding sequences indicate that these viruses were closely related to those identified from cattle in the same farms and to those previously published from the same region. The findings from this study demonstrate that SR should be considered when developing FMD risk-based surveillance and control strategies in Nigeria.
Aging and the Spectral Properties of Brain Hemodynamics
Authors: Park Ki Yun , Snyder Abraham Z , Goyal Manu S , Laumann Timothy O , Lee John J , Adeyemo Babatunde , Metcalf Nicholas , Vlassenko Andrei G , Shimony Joshua S , Leuthardt Eric C
Published: December 2024

Cerebral glucose metabolism (CMRGlc) systematically decreases with advancing age. We sought to identify correlates of decreased CMRGlc in the spectral properties of fMRI signals imaged in the task-free state. We analyzed lifespan resting-state fMRI data acquired in 455 healthy adults (ages 18-87 years) and cerebral metabolic data acquired in a separate cohort of 94 healthy adults (ages 25-45 years, 65-85 years). We characterized the spectral properties of the fMRI data in terms of the relative predominance of slow vs. fast activity using the spectral slope (SS) measure. We found that the relative proportion of fast activity increases with advancing age (SS flattening) across most cortical regions. The regional distribution of spectral slope was topographically correlated with CMRGlc in young adults. Notably, whereas most older adults maintained a youthful pattern of SS topography, a distinct subset of older adults significantly diverged from the youthful pattern. This subset of older adults also diverged from the youthful pattern of CMRGlc metabolism. This divergent pattern was associated with T2-weighted signal changes in frontal lobe white matter, an independent marker of small vessel disease. These findings suggest that BOLD signal spectral slope flattening may represent a biomarker of age-associated neurometabolic pathology.
Revealing long-range heterogeneous organization of nucleoproteins with N6-methyladenine footprinting
Authors: Yang Wentao , Wang Xueqing David , Wenger Aaron M , Fan Wei , Yu Jingqi , Liu Yifan , Dou Yali
Published: December 2024

A major challenge in epigenetics is uncovering the dynamic distribution of nucleosomes and other DNA-binding proteins, which plays a crucial role in regulating cellular functions. Established approaches such as ATAC-seq, ChIP-seq, and CUT&RUN provide valuable insights but are limited by the ensemble nature of their data, masking the cellular and molecular heterogeneity that is often functionally significant. Recently, long-read sequencing technologies, particularly Single Molecule, Real-Time (SMRT/PacBio) sequencing, have introduced transformative capabilities, such as N6-methyladenine (6mA) footprinting. This technique enables the detection of joint binding events and long-range chromatin organization on individual DNA molecules spanning multiple kilobases. Despite the potential of 6mA footprinting, existing analytical tools for 6mA detection in SMRT sequencing data suffer from significant limitations in both performance and applicability, especially with the latest sequencing platform. To address these gaps, we developed a novel 6mA-calling pipeline based on polymerase kinetics analysis. Our approach significantly outperforms current tools in terms of accuracy and computational efficiency, setting a new benchmark for 6mA detection. Utilizing our optimized experimental and computational framework, we extensively mapped nucleosome positioning and transcription factor occupancy at the single-molecule level, revealing critical features of the transcription-associated epigenetic landscape. Additionally, our work established high-resolution, long-range binding events in mitochondrial DNA, revealing simultaneous loading of two sets of replication machinery onto the displacement loop (D-loop). Our study highlights the potential of 6mA footprinting in capturing the coordinate binding of nucleoproteins and unraveling heterogeneous epigenetic states with unprecedented resolution.
UltimateSynth: MRI Physics for Pan-Contrast AI
Authors: Adams Rhea , Zhao Walter , Hu Siyuan , Lyu Wenjiao , Huynh Khoi Minh , Ahmad Sahar , Ma Dan , Yap Pew-Thian
Published: December 2024

Magnetic resonance imaging (MRI) is commonly used in healthcare for its ability to generate diverse tissue contrasts without ionizing radiation. However, this flexibility complicates downstream analysis, as computational tools are often tailored to specific MRI types and lack generalizability across the full spectrum of scans used in healthcare. Here, we introduce a versatile framework for the development and validation of pan-contrast AI models that can exhaustively cater to the full spectrum of scans achievable with MRI, enabling model deployment across scanner models, scan types, and age groups. Core to our framework is UltimateSynth, a technology that combines tissue physiology and MR physics in synthesizing realistic images across a comprehensive range of contrasts to bolster the AI development life cycle through efficient data labeling, generalizable model training, and thorough performance benchmarking. UltimateSynth is a platform for pan-contrast generalization of contrast-specific tools. We showcase the effectiveness of UltimateSynth by training an off-the-shelf U-Net to generalize anatomical segmentation across over 150,000 unique MRI contrasts, achieving robust tissue volumetric quantification with exceptionally low variability below 2%.
Comparative Analysis of Neural Decoding Algorithms for Brain-Machine Interfaces
Authors: Shevchenko Olena , Yeremeieva Sofiia , Laschowski Brokoslaw
Published: December 2024

Accurate neural decoding of brain dynamics remains a significant and open challenge in brain-machine interfaces. While various signal processing, feature extraction, and classification algorithms have been proposed, a systematic comparison of these is lacking. Accordingly, here we conducted one of the largest comparative studies evaluating different combinations of state-of-the-art algorithms for motor neural decoding to find the optimal combination. We studied three signal processing methods (i.e., artifact subspace reconstruction, surface Laplacian filtering, and data normalization), four feature extractors (i.e., common spatial patterns, independent component analysis, short-time Fourier transform, and no feature extraction), and four machine learning classifiers (i.e., support vector machine, linear discriminant analysis, convolutional neural networks, and long short-term memory networks). Using a large-scale EEG dataset, we optimized each combination for individual subjects (i.e., resulting in 672 total experiments) and evaluated performance based on classification accuracy. We also compared the computational and memory storage requirements, which are important for real-time embedded computing. Our comparative analysis provides novel insights that help inform the design of next-generation neural decoding algorithms for brain-machine interfaces used to interact with and control robots and computers.
Hormetic curve of dietary mono- and disaccharide content determines weight gain, gut microbiota composition and cognitive ability in mice
Authors: Bartochowski Piotr , Chwastek Jakub , Zglinicki Bartosz , Pietrzyk Olga , Olech-Kochańczyk Gabriela , Szewc Monika , Bartelik Aleksandra , Torres Julio C. , Karpinski Adam , Jaholkowski Piotr , Klejman Agata , Kochańczyk Marek , Bulska Ewa , Gałęcka Mirosława , Kursa Miron , Konopka Anna , Kiryk Anna , Konopka Witold
Published: December 2024

Hormesis is defined as dose response phenomenon characterized by low-dose stimulation and high-dose inhibition (Calabrese & Mattson, 2017). To date, low doses of several stressors (intermittent fasting, caloric restriction or selected phytochemicals) have been shown to exert beneficial effects on health (Martin et al., 2006). In the present study, we aimed to determine hormetic factors in a series of diets used in mice. We found that animals fed high-sugar diet (HSD) or high-fat diet (HFD) containing relatively high amounts of mono- and disaccharides become obese compared to animals fed standard diet (STAND) or ketogenic diet (KD) containing low doses of these compounds. Underlying the observed metabolic phenotype may be changes in the composition of the intestinal microbiota, showing u-shaped features in selected species. It is noteworthy that a short-term dietary regimen of several weeks resulted in difficulties in achieving effective scores on a complex cognitive test based on spatial procedural acquisition in the HSD and HFD groups. Our data identify dietary mono- and disaccharide content (commonly known as sugars) as a critical hormetic factor with beneficial/harmful effects at multiple levels of body function.
CLE4 peptide hormone regulatesde novoshoot regeneration in potato
Authors: Gancheva Maria , Lutova Ludmila
Published: December 2024

Background

De novoshoot regeneration involves reconstitution of stem cells under control of stem cell regulators. The WUSCHEL (WUS) transcription factor acts as a master regulator ofde novoshoot regeneration controlling genotype-dependent regeneration efficiency. Previously we found that potato plants overexpressing theStCLE4gene encodingSolanum tuberosumCLAVATA3/EMBRYO SURROUNDING REGION-RELATED peptide hormone exhibited awus-like phenotype with inhibited growth of the shoot apical meristem. We hypothesized that StCLE4 could also modulatede novoshoot regeneration.

Methods and results

In this study the role of the StCLE4 peptide inde novoshoot regeneration was studied by CRISPR/Cas9 mutant analysis, evaluation of overexpression effects and gene expression analysis. We found thatcle4mutation enhanced shoot regeneration in potato.

Conclusions

We have found a gene in potato, the loss of which can lead to increased shoot formation. These results can be used to improve the efficiency of shoot regeneration in potato.
Chemical perturbations impacting histone acetylation govern colorectal cancer differentiation
Authors: Likasitwatanakul Pornlada , Li Zhixin , Doan Paul , Spisak Sandor , Raghawan Akhouri Kishore , Liu Qi , Liow Priscilla , Lee Sunwoo , Chen David , Bala Pratyusha , Sahgal Pranshu , Aitymbayev Daulet , Thalappillil Jennifer S. , Papanastasiou Malvina , Hawkins William , Carr Steven A. , Park Haeseong , Cleary James M. , Qi Jun , Sethi Nilay S.
Published: December 2024

Dysregulated epigenetic programs that restrict differentiation, reactivate fetal genes, and confer phenotypic plasticity are critical to colorectal cancer (CRC) development. By screening a small molecule library targeting epigenetic regulators using our dual reporter system, we found that inhibiting histone deacetylase (HDAC) 1/2 promotes CRC differentiation and anti-tumor activity. Comprehensive biochemical, chemical, and genetic experiments revealed that on-target blockade of the HDAC1/2 catalytic domain mediated the differentiated phenotype. Unbiased profiling of histone posttranslational modifications induced by HDAC1/2 inhibition nominated acetylation of specific histone lysine residues as potential regulators of differentiation. Genome-wide assessment of implicated marks indicated that H3K27ac gains at HDAC1/2-bound regions associated with open chromatin and upregulation of differentiation genes upon HDAC1/2 inhibition. Disrupting H3K27ac by degrading acetyltransferase EP300 rescued HDAC1/2 inhibitor-mediated differentiation of a patient-derived CRC model using single cell RNA-sequencing. Genetic screens revealed that DAPK3 contributes to CRC differentiation induced by HDAC1/2 inhibition. These results highlight the importance of specific chemically targetable histone modifications in governing cancer cell states and epigenetic reprogramming as a therapeutic strategy in CRC.

BRIEF SUMMARY

HDAC1/2 inhibition promotes colorectal cancer differentiation via gains in H3K27ac, which can be reversed by blocking its acetyltransferase EP300.
UniFORM: Towards Universal Immunofluorescence Normalization for Multiplex Tissue Imaging
Authors: Wang Kunlun , Ait-Ahmad Kaoutar , Kupp Samuel D , Sims Zachary , Cramer Eric , Sayar Zeynep , Yu Jessica , Wong Melissa H. , Mills Gordon B. , Eksi S. Ece , Chang Young Hwan
Published: December 2024

Multiplexed tissue imaging (MTI) technologies enable high-dimensional spatial analysis of tumor microenvironments but face challenges with technical variability in staining intensities. Existing normalization methods, including z-score, ComBat, and MxNorm, often fail to account for the heterogeneous, right-skewed expression patterns of MTI data, compromising signal alignment and downstream analyses. We present UniFORM, a non-parametric, Python-based pipeline for normalizing both feature- and pixel-level MTI data. UniFORM preserves marker intensity distribution shapes while maintaining positive population proportions without prior assumptions and uses automated normalization. Benchmarking across two distinct MTI platforms and datasets demonstrates that UniFORM outperforms existing methods in mitigating batch effects while maintaining biological signal fidelity. This is evidenced by improved marker distribution alignment, enhanced kBET scores, and improved downstream analyses such as UMAP visualizations and Leiden clustering. UniFORM also introduces a novel guided fine-tuning option for complex and heterogeneous datasets. Although optimized for fluorescence-based platforms, UniFORM provides a scalable and robust solution for MTI data normalization, enabling accurate and biologically meaningful interpretations.
Behavioural biomechanics: leaf-cutter ant cutting behaviour depends on leaf edge geometry
Authors: Püffel Frederik , Kang Victor , Yap Mia , Shojaeifard Mohammad , Bacca Mattia , Labonte David
Published: December 2024

Leaf-cutter ants cut fresh leaves to grow a symbiotic fungus as crop. During cutting, one mandible is typically anchored onto the leaf lamina while the other slices through it like a knife. When initiating cuts into the leaf edge, however, foragers sometimes deviate from this behaviour, and instead used their mandibles symmetrically, akin to scissors.In-vivobehavioural assays revealed that the preference for either of the two cutting strategies depended on leaf edge geometry, and differed between natural leaf margins that were straight or serrated with notch-like folds: leaf-cutter ants displayed a strong preference for scissor-cutting when leaf edges were straight or had wide notches. This preference, however, reversed in favour of knife-cutting when notches were narrow. To investigate whether this behavioural difference had a mechanical origin, we mimicked knife-cutting inex-vivocutting experiments: for wide notches, all but the sharpest mandibles failed to initiate cuts, or only did so at large forces, caused by substantial leaf buckling and bending. This increased force demand would substantially limit the ability of foragers to cut leaves, and so reduce the colony’s access to food sources. Scissor-cutting may thus be an adaptation to the mechanical difficulties associated with bending and buckling of thin leaves.