bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: a prospective cohort study
Authors: Wang Shuai-Kang , Wang Qi-Jun , Wang Peng , Li Xiang-Yu , Cui Peng , Wang Dong-Fan , Chen Xiao-Long , Kong Chao , Lu Shi-Bao 
Published: May 2024

Background:
Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. Enhanced recovery after surgery (ERAS) can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains.

Materials and methods:
An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes, and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay after surgery.

Results:
A total of 245 patients (age of 79.8±3.4 year) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between nonfrail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery.

Conclusion:
Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.
In dystrophicmdxhindlimb muscles where fibrosis is limited versican haploinsufficiency transiently improves contractile function without decreasing inflammation
Authors: Debruin Danielle , McRae Natasha L. , Addinsall Alex B. , McCulloch Daniel R. , Barker Robert G. , Hayes Alan , Murphy Robyn M. , Stupka Nicole 
Published: May 2024

ABSTRACTThe provisional matrix protein versican is upregulated in Duchenne muscular dystrophy. Versican heightens inflammation in fibrotic diseases and is involved in myogenesis. In fibrotic diaphragm muscles from dystrophicmdxmice, versican reduction attenuated macrophage infiltration and improved contractile function. We investigated the association between versican andmdxhindlimb muscle pathology, where inflammation and regeneration are increased but fibrosis is minimal. Immunohistochemistry and qRT-PCR were used to assess how fiber type and glucocorticoids (α-methylprednisolone) modulate versican expression. Femalemdxand male versican haploinsufficient (hdf) mice were bred resulting in malemdx-hdf andmdx(control) pups. Versican expression, contractile function, and pathology were evaluated in fast extensor digitorum longus (EDL) and slow soleus muscles, excised under medetomidine-midazolam- fentanyl anesthesia.Versican immunoreactivity was highest in soleus muscles.VersicanmRNA transcripts were reduced by α-methylprednisolone in soleus, but not EDL, muscles. Versican expression was decreased in soleus muscles from 6-week-oldmdx-hdf mice leading to increased force output and a modest reduction in fatiguability. These functional benefits were not accompanied by decreased inflammation; muscle architecture, regeneration markers, and fiber type also did not differ between genotypes. Improvements in soleus function were lost in adult (20-week-old)mdx-hdf mice with no significant effect of versican haploinsufficiency on macrophage infiltration and regeneration markers.Soleus muscles from juvenilemdxmice were most responsive to pharmacological or genetic approaches targeting versican; however, the benefits of versican reduction were limited due to low fibrosis. Pre-clinical matrix research in dystrophy should account for muscle phenotype and the interdependence between the fibrosis and inflammation.NEW & NOTEWORTHYThe proteoglycan versican is upregulated in muscular dystrophy. In fibrotic diaphragm muscles frommdxmice, versican reduction attenuated macrophage infiltration and improved performance. Here, in hindlimb muscles from 6- and 20-week-oldmdxmice, where pathology is mild, versican reduction did not decrease inflammation and contractile function improvements were limited to juvenile mice. In dystrophicmdxmuscles, the association between versican and inflammation is mediated by fibrosis, demonstrating interdependence between the immune system and extracellular matrix.
Polygenic prediction and gene regulation networks
Authors: Poyatos Juan F 
Published: May 2024

AbstractExploring the degree to which phenotypic variation, influenced by intrinsic nonlinear biological mechanisms, can be accurately captured using statistical methods is essential for advancing our comprehension of complex biological systems and predicting their functionality. Here, we examine this issue by combining a computational model of gene regulation networks with a linear additive prediction model, akin to polygenic scores utilized in genetic analyses. Inspired by the variational framework of quantitative genetics, we create a population of individual networks possessing identical topology yet showcasing diversity in regulatory strengths. By discerning which regulatory connections determine the prediction of phenotypes, we contextualize our findings within the framework of core and peripheral causal determinants, as proposed by the omnigenic model of complex traits. We establish connections between our results and concepts such as global sensitivity and local stability in dynamical systems, alongside the notion of sloppy parameters in biological models. Furthermore, we explore the implications of our investigation for the broader discourse surrounding the role of epistatic interactions in the prediction of complex phenotypes.Author SummaryThis research delves into how well statistical methods can capture phenotypic variation influenced by nonlinear biological mechanisms. The study combines a computational model of gene regulation networks with a linear additive prediction model, similar to polygenic scores used in genetic analysis. By creating a population of individual networks with identical topology but varying regulatory strengths, the research identifies key regulatory connections that predict phenotypes. The findings are framed within the omnigenic model of complex traits, distinguishing core and peripheral causal determinants. The study also links its results to concepts like global sensitivity and local stability in dynamical systems, as well as sloppy parameters in biological models. Additionally, it examines the implications for understanding the role of epistatic interactions in predicting complex phenotypes. This work enhances our understanding of complex biological systems and their functionality.
EFFECT OF AYAHUASCA ON EXPERIMENTAL MODELS OF ETHANOL ADDICTION AND IMMUNOHISTOCHEMISTRY ANALYSIS IN RODENTS
Authors: Distefano Wiltenburg Victor , Morales-Lima Gabriela , Sousa Santos Aline Valéria , Bermúdez Echeverry Marcela , Cardoso Cruz Fábio , de Oliveira Silveira Gabriela , Yonamine Maurício , Ayako Tiba Paula , Rieli Mendes Fúlvio 
Published: May 2024

AbstractAyahuasca, a psychoactive brew originally used ritually and therapeutically by various traditional peoples in the Amazon, is receiving special attention for its potential therapeutic effects on addiction. This study investigates the effects of lyophilized ayahuasca in alcohol-induced animal model, examining behavioral, pharmacological, and neurobiological aspects. Phytochemical analysis confirmed the presence of β-carbolines and dimethyltryptamine, with all compound’s levels within literature ranges. Pharmacological screening revealed dose-dependent behavioral changes, with the highest dose inducing transient effects. Motor coordination deficits were observed at the highest dose, consistent with pharmacological screening. Pretreatment with ayahuasca prevented ethanol-induced conditioned place preference, suggesting anti-addictive potential. Immunoreactivity analysis revealed no significant changes in DeltaFosB and c-Fos expression in the nucleus accumbens core and shell subsections. This study suggests low acute toxicity of ayahuasca, motor coordination impairment at high doses, and potential anti-addictive effects in preventing ethanol-induced conditioned place preference. These findings contribute to the understanding of the pharmacological and behavioral effects of ayahuasca and highlight the need for further research and clinical studies to elucidate its therapeutic potential in substance use disorders.
Effects of longitudinal bending stiffness and midsole foam on running energetics
Authors: Perry Damion , Lino Herlandt , Bertschy Montgomery , Hoogkamer Wouter 
Published: May 2024

AbstractBackgroundAdvanced footwear technology has become commonplace in the competitive running world. However, a systematic exploration of the effects of each of the primary components has not yet been presented.PurposeTo quantify running economy and step parameters in four different shoe conditions: PEBA shoes with plate, PEBA shoes without plate, EVA shoes with plate and EVA shoes without plate.MethodsParticipants ran at 14 km/h (n = 8 males) or 12 km/h (n = 6 females) on a treadmill. The shoe order was randomly assigned for the four shoe conditions, where the participants wore each shoe twice in a mirrored order.ResultsThere was a significant reduction in metabolic power (1.0%) associated with the presence of a plate, as well as a similar reduction based on foam type (1.0%). However, there was no significant interaction between presence of plate and foam type. Adding a plate significantly reduced metabolic power for EVA by 1.3% but not for PEBA. PEBA foam significantly reduced metabolic power by 1.3% in shoes without a plate, but not for the shoes with a plate. Step frequency and contact time were similar between shoes and not correlated to running economy improvements.ConclusionsStarting from a baseline condition with traditional foam without a plate, either adding a plate or using PEBA foam improved running economy with a similar amount (1.3%). Adding the alternate second feature non-significantly improved running economy with an additional 0.6%. The benefit of both technologies combined (1.9%) was smaller than the sum of its parts (1.3% each).Key pointsThe use of a PEBA foam midsole or the addition of a carbon fiber plate improves running economy a similar amount when compared to a traditional EVA running shoe without a plate.Contrary to our hypothesis, the benefit of both technologies combined (1.9%) was smaller than the sum of its parts (1.3% each).
A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis
Authors: Ediriwickrema Asiri , Nakauchi Yusuke , Fan Amy C. , Köhnke Thomas , Hu Xiaoyi , Luca Bogdan A. , Kim YeEun , Ramakrishnan Sreejith , Nakamoto Margaret , Karigane Daiki , Linde Miles H. , Azizi Armon , Newman Aaron M. , Gentles Andrew J. , Majeti Ravindra 
Published: May 2024

SummaryHematopoietic multipotent progenitors (MPPs) regulate blood cell production to appropriately meet the biological demands of the human body. Human MPPs remain ill-defined whereas mouse MPPs have been well characterized with distinct immunophenotypes and lineage potencies. Using multiomic single cell analyses and complementary functional assays, we identified new human MPPs and oligopotent progenitor populations within Lin-CD34+CD38dim/lo adult bone marrow with distinct biomolecular and functional properties. These populations were prospectively isolated based on expression of CD69, CLL1, and CD2 in addition to classical markers like CD90 and CD45RA. We show that within the canonical Lin-CD34+CD38dim/loCD90CD45RA-MPP population, there is a CD69+ MPP with long-term engraftment and multilineage differentiation potential, a CLL1+ myeloid-biased MPP, and a CLL1-CD69-erythroid-biased MPP. We also show that the canonical Lin-CD34+CD38dim/loCD90-CD45RA+ LMPP population can be separated into a CD2+ LMPP with lymphoid and myeloid potential, a CD2-LMPP with high lymphoid potential, and a CLL1+ GMP with minimal lymphoid potential. We used these new HSPC profiles to study human and mouse bone marrow cells and observe limited cell type specific homology between humans and mice and cell type specific changes associated with aging. By identifying and functionally characterizing new adult MPP sub-populations, we provide an updated reference and framework for future studies in human hematopoiesis.
Unequal genetic redundancies among MYC bHLH transcription factors underlie seedling photomorphogenesis in Arabidopsis
Authors: Garhwal Vikas , Das Sreya , Gangappa Sreeramaiah N. 
Published: May 2024

SummaryLight is one of the most critical ecological cues controlling plant growth and development. Plants have evolved complex mechanisms to cope with fluctuating light signals. In Arabidopsis, bHLH transcription factors MYC2, MYC3, and MYC4 have been shown to play a vital role in protecting plants against herbivory and necrotrophic pathogens. While the role of MYC2 in light-mediated seedling development has been studied in some detail, the role of MYC3 and MYC4 still needs to be discovered. Here, we show that MYC4 negatively regulates seedling photomorphogenesis, while the MYC3 function seems redundant. However, the genetic analysis reveals that MYC3/MYC4 together act as positive regulators of seedling photomorphogenic growth as themyc3myc4double mutants showed exaggerated hypocotyl growth compared tomyc4single mutants and Col-0. Intriguingly, the loss ofMYC2function in themyc3myc4double mutant background (myc2myc3myc4) resulted in further enhancement in the hypocotyl growth thanmyc3myc4double mutants in WL, BL and FRL, suggesting that MYC2/3/4 together play an essential and positive role in meditating optimal seedling photomorphogenesis. Besides, MYC3/MYC4 genetically and physically interact with HY5 to partially inhibit its function in controlling hypocotyl and photo-pigment accumulation. Moreover, our results suggest that COP1 physically interacts and degrades MYC3 and MYC4 through the 26S proteasomal pathway and controls their response to dark and light for fine-tuning HY5 function and seedling photomorphogenesis.
Optimized Dosing and Delivery of Bacteriophage Therapy for Wound Infections
Authors: Lin Yung-Hao , Dharmaraj Tejas , Chen Qingquan , Echterhof Arne , Manasherob Robert , Zhang Lucy J. , de Leeuw Cas , Peterson Nana A. , Stannard Whitney , Li Zhiwei , Hajfathalian Maryam , Hargil Aviv , Martinez Hunter A. , Pourtois Julie , Chang Tony H. W. , Blankenberg Francis G. , Amanatullah Derek , Chaudhuri Ovijit , Bollyky Paul L. 
Published: May 2024

AbstractLytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistantPseudomonas aeruginosa.However, the optimal dosing and delivery strategies for phage therapy remain unclear. In a mouse wound infection model, we investigated the impact of dose, frequency, and administration route on the efficacy of phage therapy. We find that topical but not intravenous delivery is effective in this model. High-doses of phage reduces bacterial burden more effectively than low-doses, and repeated dosing achieves the highest eradication rates. Building on these insights, we developed “HydroPhage”, a hyaluronan-based hydrogel system that uses dynamic covalent crosslinking to deliver high-titre phages over one week. HydroPhage eradicates infections five times more effectively than intravenous injection. We conclude that hydrogel-based sustained phage delivery enhances the efficacy of phage therapy and offers a practical, well-tolerated option for topical application.
Melanoma-specific mutation hotspots in distal, non-coding, promoter-interacting regions implicate novel candidate driver genes
Authors: Pudjihartono Michael , Pudjihartono Nicholas , O’Sullivan Justin M. , Schierding William 
Published: May 2024

AbstractInvestigations of the non-coding region are essential for uncovering the full spectrum of genetic drivers in melanoma. Here, we map distal, non-coding, promoter-interacting regulatory elements using Hi-C data from melanoma cells and integrating these with whole-genome sequence and gene expression data from the Pan Cancer Analysis of Whole Genomes. We identified eight recurrently mutated hotspots that are melanoma-specific, alter transcription factor binding motifs, and affect the expression of genes (e.g.HSPB7,CLDN1, ADCY9andFDXR) previously implicated as tumor suppressors/oncogenes. Our study integrates multiple levels of biological data to uncover novel melanoma-specific non-coding candidate drivers beyond the well-characterizedTERTpromoter.
Cellulose Rich Food Leads Anxiety through Gut-Brain Axis-mediated Amygdalar Dopamine Upregulation
Authors: Ito Kaede , Hosoki Haruka , Kasai Yuya , Sasaki Hiroyuki , Haraguchi Atsushi , Shibata Shigenobu , Nozaki Chihiro 
Published: May 2024

AbstractIt is widely said that healthy intestinal environment takes essential role for better mental condition. One of the known dietary nutrients which maintains intestinal environment is the dietary fiber. Recent study showed that maintaining intestinal environment by dietary fiber succeeded to alleviate the psychiatric disorder symptoms in animals. However, such effects have only been reported with soluble fiber, which is highly fermentable and promotes short-chain fatty acid (SCFA) production, and not with insoluble fiber. Therefore, we aimed to verify whether insoluble fiber, such as cellulose, can alter emotion via changes in the gut. We divided mice into two groups and fed either standard diet (SD, contains both insoluble and soluble dietary fibers) or cellulose rich diet (CRD, contains cellulose alone as the dietary fibers). The CRD-fed mice displayed 1) the increased the anxiety-like behavior accompanied with 2) the modified amygdalar dopamine signaling. We further found the decreased intestinal SCFA levels along with intestinal permeability, dysmotility and hypersensitivity in CRD-fed mice. These behavioral and physiological effect of CRD has been completely abolished in vagotomized mice, indicating the direct link between intestinal environment exacerbation to the emotion through gut-brain axis. Additionally, the opioid antagonist abolished the CRD-induced anxiety, suggesting the involvement of opioidergic system to the anxiety which may evoked by increased amygdalar dopamine levels. Altogether, our findings suggest that consumption of cellulose alone as the dietary fiber may evoke intestinal abnormalities which fires the vagus nerve then opiodergic system and amygdalar dopamine upregulation, resulting in the enhancement of anxiety.Graphical Abstract: Possible mechanism of CRD-induced anxiety unveiled by current studyOur study clarified that long-consumption of cellulose-rich food (CRD) will lead decrease of SCFAs which may cause the intestinal disability, including decreased motility and increased intestinal permeability as well as upregulation of TRPA1 and SGLT1. These physiological modifications resulted as the intestinal hypersensitivity, which possibly overstimulate the vagal transmission which may activate endogenous opioidergic systems such as enkephalin (Enk) at the nucleus tractus solitarii (NTS). The activation of opioidergic system may suppress the GABAergic neuron in ventral tegmental area (VTA), resulting in the excess release of dopamine and further receptor modification in amygdala (Amyg), which might in the end cause the characteristic anxiety. The figure was created withBioRender.com.
Comparative genomics of three non-hematophagous leeches (Whitmaniaspp.): focusing on antithrombotic genes
Authors: Zhao Fang , Huang Zuhao , Tang Lizhou , He Bo , Liu Zichao , Lin Gonghua 
Published: May 2024

AbstractLeeches are well known for their blood-feeding habits and are widely used for medicinal purposes as they secrete various antithrombotic substances. However, some leeches such asWhitmaniaspp. exhibit non-hematophagous feeding habits and their significance for medicinal use is debated. In this study, we provide chromosome-level genomes of two non-hematophagous leechesWhitmania acranulataandWhitmania laevis, and combined with our previous results ofWhitmania pigra, we systematically analyzed the similarities and differences on the genomes and especially their antithrombotic genes among the three non-hematophagousWhitmanialeeches. ForW. acranulata,W. laevis, andW. pigra, the genome size (181.72 Mb, 173.87 Mb, and 173.56), the percentage of repeat sites (29.55%, 28.28%, and 27.02%), and the number of protein-coding genes (27,068, 23,805, and 24,156) were close to each other, respectively. In contrast, both the total number of the antithrombotic genes (100, 63, and 79), and the detailed constitutes of different antithrombotic gene families were obviously different among the three leeches. There were also massive genetic variations among the members within each antithrombotic gene/protein family. RNA-Seq-based gene expression estimation showed that the expression profiles of the antithrombotic gene families were apparently different among the three leeches. This is the most comprehensive comparison of the genomes and antithrombic biomacromolecules for theWhitmanialeeches to date. Our results will greatly facilitate the evolutionary research and application of leech derivatives for medical and pharmaceutical purposes of thrombosis.
Extensive folding variability between homologous chromosomes in mammalian cells
Authors: Irastorza-Azcarate Ibai , Kukalev Alexander , Kempfer Rieke , Thieme Christoph J. , Mastrobuoni Guido , Markowski Julia , Loof Gesa , Sparks Thomas M. , Brookes Emily , Natarajan Kedar Nath , Sauer Stephan , Fisher Amanda G. , Nicodemi Mario , Ren Bing , Schwarz Roland F. , Kempa Stefan , Pombo Ana 
Published: May 2024

AbstractGenetic variation and 3D chromatin structure have major roles in gene regulation. Due to challenges in mapping chromatin conformation with haplotype-specific resolution, the effects of genetic sequence variation on 3D genome structure and gene expression imbalance remain understudied. Here, we applied Genome Architecture Mapping (GAM) to a hybrid mouse embryonic stem cell (mESC) line with high density of single nucleotide polymorphisms (SNPs). GAM resolved haplotype-specific 3D genome structures with high sensitivity, revealing extensive allelic differences in chromatin compartments, topologically associating domains (TADs), long-range enhancer-promoter contacts, and CTCF loops. Architectural differences often coincide with allele-specific differences in gene expression, mediated by Polycomb repression. We show that histone genes are expressed with allelic imbalance in mESCs, are involved in haplotype-specific chromatin contact marked by H3K27me3, and are targets of Polycomb repression through conditional knockouts of Ezh2 or Ring1b. Our work reveals highly distinct 3D folding structures between homologous chromosomes, and highlights their intricate connections with allelic gene expression.