bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung microbiome alterations in patients with anti-Jo1 antisynthetase syndrome and interstitial lung disease
Authors: Quintero-Puerta Teresa , Lira-Lucio Juan Alberto , Falfán-Valencia Ramcés , Vega-Sánchez Ángel E. , Márquez-García Eduardo , Mejía Mayra , Bautista-Becerril Brandon , Rojas-Serrano Jorge , Ramos-Martínez Espiridión , Buendía-Roldán Ivette , Pérez-Rubio Gloria
Published: December 2023

Aim

To characterize the lung microbiome in the bronchoalveolar lavage fluid (BALF) of patients with Antisynthetase Syndrome (ASSD) according to anti-Jo1 autoantibody positivity and evaluate the correlation with differential cell count and other bacterial genera in BALF.

Methods

We sequenced the 16S ribosomal RNA gene in the BALF of anti-Jo1-positive (JoP, n=6) and non-Jo1-positive (NJo, n=17) patients, and the differential cell count in BALF was evaluated. The Spearman’s correlation was calculated for the quantitative variables and abundance of bacterial species.

Results

The Veillonella genus showed a significant decrease (p<0.01) in JoP (2.2%) in comparison to NJo (4.1%) patients. The correlation analysis showed several high (rho ≥ ± 0.7) and significant (p < 0.05) correlations. We analyzed the results obtained for the Veillonella genera and other study variables. The JoP group showed that the abundance of Veillonella had a high negative correlation with macrophages (rho = - 0.77) and a positive correlation with eosinophils (rho = 0.77), lymphocytes (rho = 0.77), and Prevotella (rho = 1).

Conclusions

The lung microbiome in ASSD patients differs and may affect cell composition, contributing to lung damage mechanisms. The presence of anti-Jo1 autoantibodies showed a low abundance of Veillonella. This genus had a strong and positive correlation with Prevotella abundance and levels of eosinophils and lymphocytes, and it showed a strong negative correlation with the percentage of macrophages.
Metabolomics reveals the mechanism of action of meropenem and amikacin combined in the treatment of Pseudomonas aeruginosa
Authors: Yang Hai , Huang Zhen , Yue Jiali , Chen Jianqi , Yu Mingming , Qu Chengming
Published: December 2023

The treatment of Pseudomonas aeruginosa infection often involves the combined use of β-lactam and aminoglycoside antibiotics. In this study, we employed metabolomic analysis to investigate the mechanism responsible for the synergistic activities of meropenem/amikacin combination therapy against multidrug-resistant P. aeruginosa strains harboring OXA-50 and PAO genes. Antibiotic concentrations for meropenem (2 mg/L) monotherapy, amikacin (16 mg/L) monotherapy, and meropenem/amikacin (2/16 mg/L) combination therapy were selected based on clinical breakpoint considerations. Metabolomic analysis revealed significant alterations in relevant metabolites involved in bacterial cell membrane and cell wall synthesis within 15 min of combined drug administration. These alterations encompassed various metabolic pathways, including fatty acid metabolism, peptidoglycan synthesis, and lipopolysaccharide metabolism. Furthermore, at 1 h and 4 h, the combination therapy exhibited significant interference with amino acid metabolism, nucleotide metabolism, and central carbon metabolism pathways, including the tricarboxylic acid cycle and pentose phosphate pathway. In contrast, the substances affected by single drug administration at 1 h and 4 h demonstrated a noticeable reduction. Meropenem/amikacin combination resulted in notable perturbations of metabolic pathways essential for survival of P. aeruginosa, whereas monotherapies had comparatively diminished impacts.
Qualitative analysis of mental health conversational agents messages about autism spectrum disorder: a call for action
Authors: Aghakhani S. , Carre N. , Mostovoy K. , Shafer R. , Baeza-Hernandez K. , Entenberg G. , Testerman A. , Bunge E. L.
Published: December 2023

Background

Conversational agents (CA's) have shown promise in increasing accessibility to mental health resources. This study aimed to identify common themes of messages sent to a mental health CA (Wysa) related to ASD by general users and users that identify as having ASD.

Methods

This study utilized retrospective data. Two thematic analyses were conducted, one focusing on user messages including the keywords (e.g., ASD, autism, Asperger), and the second one with messages from users who self-identified as having ASD.

Results

For the sample of general users, the most frequent themes were “others having ASD,” “ASD diagnosis,” and “seeking help.” For the users that self-identified as having ASD (n = 277), the most frequent themes were “ASD diagnosis or symptoms,” “negative reaction from others,” and “positive comments.” There were 3,725 emotion words mentioned by users who self-identified as having ASD. The majority had negative valence (80.3%), and few were positive (14.8%) or ambivalent (4.9%).

Conclusion

Users shared their experiences and emotions surrounding ASD with a mental health CA. Users asked about the ASD diagnosis, sought help, and reported negative reactions from others. CA's have the potential to become a source of support for those interested in ASD and/or identify as having ASD.
Characteristics of undergraduate dental theses defended in Peruvian licensed universities and factors associated with their publication
Authors: Cossio-Alva Bryan Alexis , Corrales-Reyes Ibraín Enrique , Pares-Ballasco Giancarlo , Luna-Mazzola Ivo , Sánchez-Ormeño José , Laura-Lopez Nievesrosa , Villegas-Maestre José Daniel , Mejia Christian R.
Published: December 2023

Introduction

In Peru, the defense of a university thesis allow to obtain a professional degree and demonstrate the research skills of the aspirant.

Objectives

To characterize the undergraduate dental theses defended in Peruvian universities and those published in scientific journals, as well as to identify the factors associated with their publication.

Methods

A cross-sectional, analytical and observational study was conducted using a search strategy in Google Scholar. We ascertained whether the theses defended between 2015-2018 had been published in scientific journals. Prevalence ratios (aPR), 95% confidence intervals (CI 95%) and p-values were obtained using generalized linear models.

Results

Most of the theses were defended in private universities (65.9%), located in the provinces (76.7%), in 2017 (32.1%). The most studied line of research was Dental Education (n = 418; 18.4%). Of the total number of defended theses (n = 2,267), only 130 (5.7%) were published, in a total of 41 scientific journals, of which 22 are specialized in the dental field. The 130 articles received 443 citations, with an average of 3.4 citations per document. The Universidad Católica Santa María was the institution that defended the most theses (n = 372); however, the Universidad Científica del Sur presented the highest percentage of published theses (36.4%). Theses with case-control (aPR: 2.74; CI 95%: 1.07-7.01; p = 0.036) and cohort (aPR: 3.51; CI 95%: 2.02-6.11; p  < 0.001) methodological design had a higher frequency of publication; on the contrary, those executed in the community were less frequently published (aPR: 0.39; CI 95%: 0.17-0.93; p = 0.033), as well as, those with two researchers (aPR: 0.41; CI 95%: 0.18-0.92; p = 0.031), adjusted for two variables.

Conclusion

Only one in twenty theses was published. Publication was associated with the type of methodological design, the place of execution and the number of researchers.
Reproductive health in Turner’s syndrome: from puberty to pregnancy
Authors: Porcu Eleonora , Cipriani Linda , Damiano Giuseppe
Published: December 2023

Turner syndrome (TS) is a genetic pathology that affects about 1/2500 newborn females. Turner’s syndrome is characterized by highly variable genetic anomalies that consist in a partial or complete deletion of the X sexual chromosome; it can be present as a monosomy or as a mosaicism with two o three different cellular lines. 50% of the patients with Turner’s syndrome has a 45 XO karyotype while the remaining cases have karyotypes with mosaicism or X isochromosome or with partial or whole Y chromosome. This pathology is characterized by multiple anomalies that involve physical and cognitive development and in particular endocrine, cardiovascular, reproductive, auditive and visual systems. Integrity of the X chromosome in essential for fertility. In TS is accelerated germ cells apoptosis. About 30% of TS girls have some pubertal development, 10-20% undergo menarche and 2-8% go through spontaneous pregnancy. Women with TS should be informed about the risk of premature menopause and should be referred, if possible, to a specialist evaluation with a doctor expert in assisted reproductive techniques. In adolescents and in adults, Premature Ovarian Insufficiency (POI) can be evaluated clinically and biochemically with the classic combination of amenorrhea and elevated FSH concentrations (hypergonadotropic hypogonadism). However, in postpubertal adolescents and adult women, reproductive hormones may remain within the normal range before POI is clinically evident, despite significant depletion of the ovarian reserve. Today, reproductive medicine offers the opportunity of fertility preservation in women with premature ovarian insufficiency (POI). Two techniques have been suggested such as ovarian cortex cryopreservation and oocytes cryopreservation.
An updated meta-analysis of the relationship between vitamin D levels and precocious puberty
Authors: Cheng Hong , Chen Dan , Gao Hui
Published: December 2023

Background

Some studies have investigated the association between vitamin D levels and precocious puberty (PP) but with limited sample sizes and inconsistent conclusions across studies.

Methods

Until July 2022, a comprehensive electronic search of works of literature was conducted in MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). A systematic review and meta-analysis of 15 case-control studies with 2145 cases and 2063 controls was conducted to explore the relationship between vitamin D and PP. Stratified analyses by year of publication, country, diagnosis category of PP, child’s sex, and methods of 25(OH)D test were conducted.

Results

There was a negative correlation between 25(OH)D concentrations and PP in all study populations (SMD = -1.046, 95%CI = -1.366, -0.726). The pooled SMD remained significant in Chinese studies (SMD = -1.113, 95%CI = -0.486, -0.741), studies published before or after 2018 (SMD = -0.9832 and -1.185, 95%CI = -2.044, -1.133 and -1.755, -0.726), studies with female children (SMD = -1.114, 95%CI = -1.446, -0.781), and studies using electrochemiluminescence to detect 25(OH)D (SMD = -0.999, 95%CI = -1.467, -0.531). Vitamin D deficiency also increased the risk of PP (OR = 1.531, 95%CI = 1.098, 2.134). Unfortunately, heterogeneity was high in all analyses, and there was some publication bias.

Conclusion

This systematic review and meta-analysis demonstrated an association between vitamin D and precocious puberty. We recommend more high-quality studies, especially prospective cohort studies with big sample sizes or some randomized controlled intervention trials, to validate the reliability of the results.
Benefit distribution of integrated regional energy systems under carbon trading mechanisms based on improved Shapley value methods
Authors: Wang Yubao , Cao Rongyu , Luo Da , Li Pengpeng , Cheng Xiang
Published: December 2023

Carbon trading mechanisms and the development of integrated energy systems are important ways to realize the “carbon peaking and carbon neutrality” goal, and the problem of benefit distribution is of paramount importance to achieving the goal. The article innovatively takes the supply side of the provincial integrated energy system as the entry point, considers the economic value of carbon, and focuses on the rational allocation of each subject obtained by comparing different methods. The paper mainly uses the Shapley value of the cooperative game and the kernel method to establish the initial allocation to the main actors, and subsequently, it considers the introduction of the risk level, resource input, environmental pollution, technological innovation, and profit of the main actors to modify the result of the benefit allocation. This paper takes the power generation data of the Xinjiang region as an example, and the results show that 1) thermal power still has the most weight among all power generation modes and obtains 522.83, 503.48, and 406.30 billion yuan under the initial, nucleolus, and modified allocation methods, respectively, and receives the most revenue. 2) Considering that the multi-factor allocation method pays more attention to the allocation of fairness, compared with the initial allocation, thermal power gains decreased by 22.29%, while wind and solar power gains were improved by 17.87% and 60.90%, respectively. The result could be a stronger push for the development and transformation of power energy. 3) The feasibility of this game as a convex game should be verified, the improvement method should be demonstrated through examples, and the results should be compared with reality. Finally, policy recommendations are proposed, which will be useful for realizing the “carbon peaking and carbon neutrality” goal and the synergistic development of integrated energy systems.
A review of natural and managed revegetation responses in two de-watered reservoirs after large dam removals on the Elwha River, Washington, USA
Authors: Chenoweth Joshua , Shafroth Patrick B. , Brown Rebecca L. , Helfield James M. , Bauman Jenise M. , Cendejas-Zarelli Sara , Werner Chhaya M. , Schuster Jarrett L. , Morgan Olivia A.
Published: December 2023

Large dam removals are increasing in frequency and the response of natural and managed revegetation is a critical consideration for managed restoration of dewatered reservoir landscapes post dam removal. The removal of two large dams on the Elwha River in 2011-2014 provides insight into reservoir revegetation. We review literature and datasets from 2012 through 2018, 1-6 years since reservoir dewatering, to compare pre-dam removal predictions on the Elwha to post-dam removal of natural revegetation, managed revegetation effects and invasive non-native vegetation response. Pre-dam removal hypotheses about natural revegetation did not predict species performance on reservoir sediments, seed rain patterns, or seed bank response. Sediment texture and landform affected multiple aspects of revegetation, including vegetation cover, species richness, woody stem densities and species composition. Reservoir drawdown timing influenced species composition and seedling densities. Predictions about managed revegetation effects were mixed. Planting trees and shrubs did not accelerate woody cover but did increase species richness. Seeding reduced non-native vegetation frequency and species richness, had no effect on vegetation cover on fine sediments, but increased vegetation cover on coarse sediments. Planting trees and shrubs during drawdown appeared to result in higher survival rates compared to plantings installed 1+ years post drawdown. Seeding Lupinus rivularis (riverbank lupine) on coarse sediments was successful and increased foliar nitrogen in planted conifers. Invasive non-native vegetation was correctly predicted to be more abundant in the Aldwell reservoir but did not preclude native species establishment in either reservoir, likely due to rapid establishment of native species and robust management that occurred before, during and after dam removal.
Climate and dispersal limitation drive tree species range shifts in post-glacial Europe: results from dynamic simulations
Authors: Zani Deborah , Lischke Heike , Lehsten Veiko
Published: December 2023

Introduction

The ability of species to colonize newly suitable habitats under rapid climate change can be constrained by migration processes, resulting in a shift of the leading edge lagging behind the ameliorating climate, i.e. migration lag. The importance and extent of such migration lags during the forest expansion after the Last Glacial Maximum (LGM) are still debated. Similarly, the relative importance of the main drivers of post-glacial vegetation dynamics (temperature, dispersal limitation, and competition) is still discussed in the literature.

Methods

We used the dynamic global vegetation model LPJ-GM 2.0 to reconstruct the range shifts of 16 competing major European tree species after the LGM (18.5 ka BP) until recent times (0 ka BP). We simulated two dispersal modes by allowing free establishment whenever the climatic conditions suited the species (free dispersal), or by accounting for migration processes in the simulated vegetation dynamics (dispersal limitation). We then calculated thermal and range shift velocities, competition at establishment, thermal and dispersal lags for each species and dispersal mode. Finally, we compared our simulated range shift velocities with pollen-derived migration rates.

Results

The simulation assuming limited dispersal resulted in more accurate migration rates as compared to pollen-derived migration rates and spreading patterns. We found no marked migration lags in the post-glacial establishment of pioneer species (Pinus sylvestris and Betula pubescens). Under the free dispersal mode, the remaining temperate species expanded rapidly and almost synchronously across central Europe upon climate warming (Bølling-Allerød interstadial). Differently, the northward spread of temperate species simulated under dispersal limitation happened mainly during the Holocene and in successive waves, with late spreaders (e.g. Fraxinus excelsior) experiencing multi-millennial dispersal lags and higher competition.

Discussion

Our simulation under dispersal constraints suggests that the post-glacial tree expansion in Europe was mainly driven by species-specific thermal requirements and dispersal capacity, which in turn affected the order of taxa establishment and thus the degree of competition. Namely, taxa with less cold-tolerance and relatively low dispersal ability experienced the highest migration lags, whereas the establishment of pioneer species was mostly in equilibrium with the climate.
Cost of mitigating climate change through reforestation in China
Authors: Zhang Xianghua , Busch Jonah , Huang Yingli , Fleskens Luuk , Qin Huiyan , Qiao Zhenhua
Published: December 2023

Reforestation is a potentially large-scale approach for removing CO2 from the atmosphere, thereby helping China achieve its goal of carbon neutrality by 2060. Although China has set ambitious national targets, the cost of mitigating climate change through reforestation has yet to be identified across space and time over the next 40 years. We construct spatially disaggregated marginal abatement cost curves for reforestation by modeling the effects of compensation for enhanced CO2 removals on reforestation. We project that carbon prices (compensation) of US$20 tCO2−1 and US$50 tCO2−1 would motivate land users in China to enhance reforestation by 3.35 Mha (2.65%) and 8.53 Mha (6.74%) respectively from 2020 to 2060 relative to the business-as-usual (BAU) scenario (127 Mha). Carbon dioxide removals through reforestation between 2020 and 2060 in China would be enhanced by 0.0124 GtCO2/yr (1.7%) at US$20 tCO2−1 or 0.0315 GtCO2/yr (4.3%) at US$50 tCO2−1, relative to the BAU scenario (0.740 GtCO2/yr). The cost potential of carbon dioxide removal demonstrates significant spatial heterogeneity. The top 10 provinces (Yunnan, Sichuan, Guangxi, Guizhou, Hunan, Guangdong, Heilongjiang, Jiangxi, Fujian, and Zhejiang), which comprise 73.19% of low-cost abatement potential, should be identified as priority areas for reforestation. Our results confirm the vast potential for low-cost CO2 removal through reforestation to address China’s carbon neutrality challenges while underscoring that targeting reforestation to regions with the greatest potential for low-cost CO2 removal would significantly reduce the cost burden.
Tree growth as an effect indicator of silvopastoral systems in the low hilly area of western Henan province, China
Authors: Liu Peisong , Cheng Fan , Wang Xinlong , Liu Zhipeng , Cheng Liping , Tong Weishuang , Qi Guang , Kou Lixuan
Published: December 2023

The low hilly area is a major landform in the west of Henan province, China, and it is suffering soil and water loss because of human activities. The silvopastoral system that combines trees and grasses has been widely used to restore this fragile area. We conducted in situ field experiments in 2011 in the low hilly area of Henan province involving pure forests of Populus simonii (PS; Salicaceae), Platycladus orientalis (PO; Cupressaceae), Quercusvariabilis (QV; Fagaceae), and Robinia pseudoacacia (RP; Fabaceae), and also with each forest tree species being combined with Medicago sativa (MS; Fabaceae) as silvopastoral systems, i.e., PS-MS, PO-MS, QV-MS, and RP-MS, respectively. We recorded tree diameter at breast height (DBH) and tree height (TH) in the years 2014–2016, 2018, 2020, and 2022 for all the different vegetation types. Tree biomass load (TBL, i.e., tree biomass per unit area) was estimated based on DBH and TH using allometric equations for each tree species. Generally, the results showed that the DBH, TH, and TBL were promoted in the silvopastoral systems PS-MS, PO-MS, and QV-MS. Specially, the DBH and TBL of PS-MS and PO-MS tended to be higher and were significantly higher than the pure forests of PS and MS, respectively, in 2014–2016; the silvopastoral systems were not significantly different from the pure forests for DBH in 2018 and 2022, and for TBL in 2018 and 2020. TH was lower in PS-MS and PO-MS than that in PS and PO in 2014–2016, while there was no difference of TH between PS-MS and PS in 2018 and 2022, and TH was higher in PO-MS than that in PO in 2018, 2020 and 2022. The DBH, TH, and TBL were all higher in QV-MS than QV. The TBL in RP-MS was non-significant or lower compared to that in RP. Moreover, TBL tended to be lower in upslope positions than downslope in the pure forests, while there was no difference in most silvopastoral systems. In summary, PS and PO may be suggested as the tree species selection in vegetation restoration processes for about five years, QV may be a better alternative for a long term, while RP is not recommended.
Liquid biopsy in non-small cell lung cancer: a meta-analysis of state-of-the-art and future perspectives
Authors: Franzi Sara , Seresini Gabriele , Borella Paolo , Raviele Paola Rafaniello , Bonitta Gianluca , Croci Giorgio Alberto , Bareggi Claudia , Tosi Davide , Nosotti Mario , Tabano Silvia
Published: December 2023

Introduction: To date, tissue biopsy represents the gold standard for characterizing non-small-cell lung cancer (NSCLC), however, the complex architecture of the disease has introduced the need for new investigative approaches, such as liquid biopsy. Indeed, DNA analyzed in liquid biopsy is much more representative of tumour heterogeneity.

Materials and methods: We performed a meta-analysis of 17 selected papers, to attest to the diagnostic performance of liquid biopsy in identifying EGFR mutations in NSCLC.

Results: In the overall studies, we found a sensitivity of 0.59, specificity of 0.96 and diagnostic odds ratio of 24,69. Since we noticed a high heterogeneity among different papers, we also performed the meta-analysis in separate subsets of papers, divided by 1) stage of disease, 2) experimental design and 3) method of mutation detection. Liquid biopsy has the highest sensitivity/specificity in high-stage tumours, and prospective studies are more reliable than retrospective ones in terms of sensitivity and specificity, both NGS and PCR-based techniques can be used to detect tumour DNA in liquid biopsy.

Discussion: Overall, liquid biopsy has the potential to help the management of NSCLC, but at present the non-homogeneous literature data, lack of optimal detection methods, together with relatively high costs make its applicability in routine diagnostics still challenging.
Inhibition of focal adhesion kinase 2 results in a macrophage polarization shift to M2 which attenuates local and systemic inflammation and reduces heterotopic ossification after polysystem extremity trauma
Authors: Rowe Cassie J. , Nwaolu Uloma , Salinas Daniela , Hong Jonathan , Nunez Johanna , Lansford Jefferson L. , McCarthy Conor F. , Potter Benjamin K. , Levi Benjamin H. , Davis Thomas A.
Published: December 2023

Introduction

Heterotopic ossification (HO) is a complex pathology often observed in combat injured casualties who have sustained severe, high energy polytraumatic extremity injuries. Once HO has developed, prophylactic therapies are limited outside of surgical excision. Tourniquet-induced ischemia injury (IR) exacerbates trauma-mediated musculoskeletal tissue injury, inflammation, osteogenic progenitor cell development and HO formation. Others have shown that focal adhesion kinase-2 (FAK2) plays a key role in regulating early inflammatory signaling events. Therefore, we hypothesized that targeting FAK2 prophylactically would mitigate extremity trauma induced IR inflammation and HO formation.

Methods

We tested whether the continuous infusion of a FAK2 inhibitor (Defactinib, PF-573228; 6.94 µg/kg/min for 14 days) can mitigate ectopic bone formation (HO) using an established blast-related extremity injury model involving femoral fracture, quadriceps crush injury, three hours of tourniquet-induced limb ischemia, and hindlimb amputation through the fracture site. Tissue inflammation, infiltrating cells, osteogenic progenitor cell content were assessed at POD-7. Micro-computed tomography imaging was used to quantify mature HO at POD-56.

Results

In comparison to vehicle control-treated rats, FAK2 administration resulted in no marked wound healing complications or weight loss. FAK2 treatment decreased HO by 43%. At POD-7, marked reductions in tissue proinflammatory gene expression and assayable osteogenic progenitor cells were measured, albeit no significant changes in expression patterns of angiogenic, chondrogenic and osteogenic genes. At the same timepoint, injured tissue from FAK-treated rats had fewer infiltrating cells. Additionally, gene expression analyses of tissue infiltrating cells resulted in a more measurable shift from an M1 inflammatory to an M2 anti-inflammatory macrophage phenotype in the FAK2 inhibitor-treated group.

Discussion

Our findings suggest that FAK2 inhibition may be a novel strategy to dampen trauma-induced inflammation and attenuate HO in patients at high risk as a consequence of severe musculoskeletal polytrauma.
Separation of GVL from GVHD -location, location, location
Authors: Teshima Takanori , Hashimoto Daigo
Published: December 2023

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for various hematologic malignancies. However, alloimmune response is a double-edged sword that mediates both beneficial graft-versus-leukemia (GVL) effects and harmful graft-versus-host disease (GVHD). Separation of GVL effects from GVHD has been a topic of intense research to improve transplant outcomes, but reliable clinical strategies have not yet been established. Target tissues of acute GVHD are the skin, liver, and intestine, while leukemic stem cells reside in the bone marrow. Tissue specific effector T-cell migration is determined by a combination of inflammatory and chemotactic signals that interact with specific receptors on T cells. Specific inhibition of donor T cell migration to GVHD target tissues while preserving migration to the bone marrow may represent a novel strategy to separate GVL from GVHD. Furthermore, tissue specific GVHD therapy, promoting tissue tolerance, and targeting of the tumor immune microenvironment may also help to separate GVHD and GVL.
Synergetic support of cartilage homeostasis via coupled thermal-pressure stimuli: a transcriptomic study in human cartilage explants
Authors: Guo Yanheng , Stampoultzis Theofanis , Pioletti Dominique P.
Published: December 2023

During daily activities, cartilage encounters complex biophysical cues upon loading. Foremost among these is the coupled stimulation of hydrostatic pressure (HP) and loading-induced temperature increase (T), which encompasses both mechanical and thermal aspects of biophysical stimulations in cartilage. While prior research on this subject has been initiated in our laboratory, the detailed mechanisms of combined HP-T effects on chondrocytes in their natural environment remain largely unexplored. Using a custom bioreactor, we applied both isolated and combined HP-T stimuli to cartilage explants obtained from a non-inflammatory adolescent knee joint. Tissue and cellular responses were evaluated through histochemical staining and transcriptomic analyses, employing bulk RNA-sequencing complemented with signaling enrichment analyses. Our findings reveal that the thermal component of the coupled HP-T stimulation predominantly regulates the chondrocytes’ transcriptional profile during the stimulation period. When coupled with HP stimulation, a peak in chondroinduction was observed. This coupling process notably boosted chondroprotection in a synergistic manner, as demonstrated by the corresponding enhanced negative regulation of apoptotic processes and increased levels of Heat Shock Protein 70 (HSPA). Our study suggests that the upregulation in protein translation and processing, triggered by thermal stimulation, may serve as an adaptive mechanism in chondrocytes to mechanical simulations, thereby contributing to the observed synergy during the coupling of these two biophysical stimuli. The results highlight the potential of integrating thermal stimulation, a natural accompanying process during cartilage deformation, in tissue engineering, cell therapy or physiotherapy.
Morphological and multi-gene phylogenetic analyses reveal five new hyphomycetes from freshwater habitats
Authors: Zhang Ya-Zhou , Chen Qi-Lei , Ma Jian , Lu Yong-Zhong , Chen Hu-Biao , Liu Ning-Guo
Published: December 2023

During the survey on freshwater hyphomycetes in Guangxi, Guizhou and Hainan Provinces, China, five fresh collections were encountered. Based on their morphology, these five isolates were identified as belonging to Hermatomyces, Kirschsteiniothelia, Paramonodictys, Pleopunctum and Sparticola. Multi-gene phylogenetic analyses were performed for each genus, which resulted in the identification of five new species, namely Hermatomyces hainanensis, Kirschsteiniothelia ramus, Paramonodictys globosa, Pleopunctum guizhouense, and Sparticola irregularis. Detailed descriptions and illustrations of the morphological characteristics of these new taxa were provided. This research enriches the biodiversity of freshwater dematiaceous hyphomycetes.
Application of artificial intelligence approaches to predict the metabolism of xenobiotic molecules by human gut microbiome
Authors: Malwe Aditya S. , Sharma Vineet K.
Published: December 2023

A highly complex, diverse, and dense community of more than 1,000 different gut bacterial species constitutes the human gut microbiome that harbours vast metabolic capabilities encoded by more than 300,000 bacterial enzymes to metabolise complex polysaccharides, orally administered drugs/xenobiotics, nutraceuticals, or prebiotics. One of the implications of gut microbiome mediated biotransformation is the metabolism of xenobiotics such as medicinal drugs, which lead to alteration in their pharmacological properties, loss of drug efficacy, bioavailability, may generate toxic byproducts and sometimes also help in conversion of a prodrug into its active metabolite. Given the diversity of gut microbiome and the complex interplay of the metabolic enzymes and their diverse substrates, the traditional experimental methods have limited ability to identify the gut bacterial species involved in such biotransformation, and to study the bacterial species-metabolite interactions in gut. In this scenario, computational approaches such as machine learning-based tools presents unprecedented opportunities and ability to predict the gut bacteria and enzymes that can potentially metabolise a candidate drug. Here, we have reviewed the need to identify the gut microbiome-based metabolism of xenobiotics and have provided comprehensive information on the available methods, tools, and databases to address it along with their scope and limitations.
Indirect regulation of topsoil nutrient cycling by groundwater depth: impacts on sand-fixing vegetation and rhizosphere bacterial communities
Authors: Hao Lianyi , Liu Xiuhua , Ji Ruiqing , Ma Yandong , Wu Puxia , Cao Qingxi , Xin Yunling
Published: December 2023

Introduction

The impact of groundwater table depth (GTD) on bacterial communities and soil nutrition in revegetated areas remains unclear.

Methods

We investigated the impacts of plant growth and soil physicochemical factors on rhizosphere bacterial communities under different GTD.

Results

The four plant growth indices (Pielou, Margalef, Simpson, and Shannon-Wiener indices) and soil water content (SWC) at the Artem and Salix sites all showed a decreasing trend with increasing GTD. Salix had a higher nutrient content than Artem. The response of plant rhizosphere bacterial communities to GTD changes were as follows. Rhizosphere bacteria at the Artem and Salix sites exhibited higher relative abundance and alpha diversity in SW (GTD < 5 m) compared than in DW (GTD > 5 m). Functional microbial predictions indicated that the rhizosphere bacterial communities ofArtemandSalixpromoted carbon metabolism in the SW. In contrast, Artem facilitated nitrogen cycling, whereas Salix enhanced both nitrogen cycling and phototrophic metabolism in the DW.

Discussion

Mantel test analysis revealed that in the SW of Artem sites, SWC primarily governed the diversity of rhizosphere and functional bacteria involved in the nitrogen cycle by affecting plant growth. In DW, functional bacteria increase soil organic carbon (SOC) to meet nutrient demands. However, higher carbon and nitrogen availability in the rhizosphere soil was observed in the SW of the Salix sites, whereas in DW, carbon nutrient availability correlated with keystone bacteria, and changes in nitrogen content could be attributed to nitrogen mineralization. This indicates that fluctuations in the groundwater table play a role in regulating microbes and the distribution of soil carbon and nitrogen nutrients in arid environments.
Genetic components of Escherichia coli involved in its complex prey-predator interaction with Myxococcus xanthus
Authors: Zhang Ning , Li Tingyi , Pan Hongwei , Wang Yipeng , Li Qi , Luan Jia , He Xuesong , Shi Wenyuan , Li Yuezhong , Wang Chuandong , Zhang Fengyu , Hu Wei
Published: December 2023

Myxococcus xanthus and Escherichia coli represent a well-studied microbial predator-prey pair frequently examined in laboratory settings. While significant progress has been made in comprehending the mechanisms governing M. xanthus predation, various aspects of the response and defensive mechanisms of E. coli as prey remain elusive. In this study, the E. coli MG1655 large-scale chromosome deletion library was screened, and a mutant designated as ME5012 was identified to possess significantly reduced susceptibility to predation by M. xanthus. Within the deleted region of ME5012 encompassing seven genes, the significance of dusB and fis genes in driving the observed phenotype became apparent. Specifically, the deletion of fis resulted in a notable reduction in flagellum production in E. coli, contributing to a certain level of resistance against predation by M. xanthus. Meanwhile, the removal of dusB in E. coli led to diminished inducibility of myxovirescin A production by M. xanthus, accompanied by a slight decrease in susceptibility to myxovirescin A. These findings shed light on the molecular mechanisms underlying the complex interaction between M. xanthus and E. coli in a predatory context.
The role of ventral tegmental area in chronic stroke rehabilitation: an exploratory study
Authors: Astrakas Loukas G. , Elbach Sabrina , Giannopulu Irini , Li Shasha , Benjafield Howard , Tzika A. Aria
Published: December 2023

Introduction

The acknowledged role of external rewards in chronic stroke rehabilitation, offering positive reinforcement and motivation, has significantly contributed to patient engagement and perseverance. However, the exploration of self-reward’s importance in this context remains limited. This study aims to investigate the functional connectivity of the ventral tegmental area (VTA), a key node in the brain’s reward circuitry, during motor task-based rehabilitation and its correlation with the recovery process.

Methods

Twelve right-handed healthy volunteers (4 men, 8 women, aged 57.4 ± 11.3 years) and twelve chronic stroke patients (5 men, 7 women, aged 48.1 ± 11.1 years) with clinically significant right-sided motor impairment (mean FM-UE score of 27.6 ± 8.7) participated. The analysis employed the CONN toolbox to assess the association between motor tasks and VTA connectivity using psychophysiological interaction (PPI).

Results

PPI analysis revealed motor-dependent changes in VTA connectivity, particularly with regions within the motor circuitry, cerebellum, and prefrontal cortex. Notably, stronger connectivity between the ipsilesional VTA and cerebellum was observed in healthy controls compared to chronic stroke patients, highlighting the importance of VTA-cerebellum interactions in motor function. Stroke patients’ motor performance was associated with VTA modulation in areas related to both motor tasks and reward processing, emphasizing the role of self-reward processes in rehabilitation. Changes in VTA influence on motor circuitry were linked to improvements in motor performance resulting from rehabilitation.

Discussion

Our findings underscore the potential of neuroimaging techniques in quantifying and predicting rehabilitation outcomes by examining self-reward processes. The observed associations between VTA connectivity and motor performance in both healthy and stroke-affected individuals emphasize the role of psychological factors, particularly self-reward, in the rehabilitation process. This study contributes valuable insights into the intricate interplay between reward circuits and motor function, highlighting the importance of addressing psychological dimensions in neurorehabilitation strategies.
Intravenous cangrelor use for neuroendovascular procedures: a two-center experience and updated systematic review
Authors: Desai Harsh , Al-Salihi Mohammed Maan , Morsi Rami Z. , Vayani Omar R. , Kothari Sachin A. , Thind Sonam , Carrión-Penagos Julián , Baskaran Archit , Tarabichi Ammar , Bonderski Veronica A. , Siegler James E. , Hahn Mary , Coleman Elisheva R. , Brorson James R. , Mendelson Scott J. , Mansour Ali , Dabus Guilherme , Hurley Michael , Prabhakaran Shyam , Linfante Italo , Kass-Hout Tareq
Published: December 2023

Background

The optimal antiplatelet therapy regimen for certain neuroendovascular procedures remains unclear. This study investigates the safety and feasibility of intravenous dose-adjusted cangrelor in patients undergoing acute neuroendovascular interventions.

Methods

We conducted a retrospective chart review of all consecutive patients on intravenous cangrelor for neuroendovascular procedures between September 1, 2020, and March 13, 2022. We also conducted an updated systematic review and meta-analysis using PubMed, Scopus, Web of Science, Embase and the Cochrane Library up to February 22, 2023.

Results

In our cohort, a total of 76 patients were included [mean age (years): 57.2 ± 18.2, males: 39 (51.3), Black: 49 (64.5)]. Cangrelor was most used for embolization and intracranial stent placement (n = 24, 32%). Approximately 44% of our patients had a favorable outcome with a modified Rankin Scale (mRS) score of 0 to 2 at 90 days (n = 25/57); within 1 year, 8% of patients had recurrent or new strokes (n = 5/59), 6% had symptomatic intracranial hemorrhage [sICH] (4/64), 3% had major extracranial bleeding events (2/64), and 3% had a gastrointestinal bleed (2/64). In our meta-analysis, 11 studies with 298 patients were included. The pooled proportion of sICH and intraprocedural thromboembolic complication events were 0.07 [95% CI 0.04 to 1.13] and 0.08 [95% CI 0.05 to 0.15], respectively.

Conclusion

Our study found that intravenous cangrelor appears to be safe and effective in neuroendovascular procedures, with low rates of bleeding and ischemic events. However, further research is needed to compare different dosing and titration protocols of cangrelor and other intravenous agents.
Geographic atrophy: pathophysiology and current therapeutic strategies
Authors: Rajanala Kalpana , Dotiwala Farokh , Upadhyay Arun
Published: December 2023

Geographic atrophy (GA) is an advanced stage of age-related macular degeneration (AMD) that leads to gradual and permanent vision loss. GA is characterized by the loss of photoreceptor cells and retinal pigment epithelium (RPE), leading to distinct atrophic patches in the macula, which tends to increase with time. Patients with geographic atrophy often experience a gradual and painless loss of central vision, resulting in difficulty reading, recognizing faces, or performing activities that require detailed vision. The primary risk factor for the development of geographic atrophy is advanced age; however, other risk factors, such as family history, smoking, and certain genetic variations, are also associated with AMD. Diagnosis is usually based on a comprehensive eye examination, including imaging tests such as fundus photography, optical coherence tomography (OCT), and fluorescein angiography. Numerous clinical trials are underway, targeting identified molecular pathways associated with GA that are promising. Recent approvals of Syfovre and Izervay by the FDA for the treatment of GA provide hope to affected patients. Administration of these drugs resulted in slowing the rate of progression of the disease. Though these products provide treatment benefits to the patients, they do not offer a cure for geographic atrophy and are limited in efficacy. Considering these safety concerns and limited treatment benefits, there is still a significant need for therapeutics with improved efficacy, safety profiles, and better patient compliance. This comprehensive review discusses pathophysiology, currently approved products, their limitations, and potential future treatment strategies for GA.
Battlefield acupuncture for chronic musculoskeletal pain in cancer survivors: a novel care delivery model for oncology acupuncture
Authors: Zhang Yi Lily , Mao Jun J. , Li Q. Susan , Weitzman Matthew , Liou Kevin T.
Published: December 2023

Introduction

Battlefield Acupuncture (BFA), a standardized auricular acupuncture protocol, is widely used for pain in the military but is not well-studied in oncology. This study examined cancer survivors who received BFA for pain.

Methods

This is a secondary analysis of a randomized trial that compared the effectiveness of BFA and electroacupuncture vs. usual care for chronic musculoskeletal pain in cancer survivors. This study focused on participants randomized to BFA. Participants received 10 weekly treatments. Needles were placed until one of these stop conditions were satisfied: ten needles were administered; pain severity decreased to ≤1 out of 10; patient declined further needling, or vasovagal reaction was observed. Pain severity was assessed using Brief Pain Inventory. Responders were those with ≥30% pain severity reduction. We examined pain location, BFA stop reason, and pain reduction of participants during the first session. We also examined which factors predicted responder status after the first session (week 1) or the full treatment (week 12).

Results

Among 143 randomized to BFA, most common pain locations were lower back (30.8%) and knee/leg (18.2%). Of 138 who initiated treatment, 41 (30.0%) received ten needles; 81 (59.1%) achieved pain ≤1; 14 (10.2%) declined further needling; and 1 (0.7%) had vasovagal reaction. BFA reduced pain severity by 2.9 points (95% CI 2.6 to 3.2) after the first session (P < 0.001). After adjusting for baseline pain severity, responders at week 1 were 2.5 times more likely to be responders at week 12, compared to those who were non-responders at week 1 (AOR 2.5, 95% CI 1.02 to 6.11, P = 0.04). Among those who achieved pain ≤1, 74% were responders at week 12, a higher proportion compared to the proportion of responders among those who received ten needles (39.5%), those who declined further needling (50%), and those with vasovagal reaction (0.0%) (P = 0.001). Those with pain in proximal joints had a higher proportion of responders at week 12, compared to those with pain in distal joints (64.2% vs. 20%, P = 0.008).

Conclusion

Specific factors may predict the likelihood of achieving meaningful pain reduction from BFA. Understanding these predictors could inform precision pain management and acupuncture delivery models.
Multisystem inflammatory syndrome in children characterized by enhanced antigen-specific T-cell expression of cytokines and its reversal following recovery
Authors: Pavan Kumar Nathella , Abbas Kadar M. , Renji Rachel M. , Venkataraman Aishwarya , Nancy Arul , Varadarjan Poovazhagi , Selladurai Elilarasi , Sangaralingam Thankgavelu , Selvam Ramya , Thimmaiah Akshith , Natarajan Suresh , Ramasamy Ganesh , Hissar Syed , Ranganathan Uma Devi , Nutman Thomas B. , Babu Subash
Published: December 2023

Background

Multisystem inflammatory syndrome (MIS) in children is considered to be a post-infectious complication of COVID-19. T-cell responses in children with this condition have not been well-studied.

Methods

We aimed to study the immune responses in children with MIS in comparison to children with acute COVID-19 and children with other infections. Whole blood was stimulated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)–specific antigens and flow cytometry was performed to examine CD4+ and CD8+ T-cell responses.

Results

Children with MIS had higher frequencies of CD4+ and CD8+ T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen–specific stimulation in comparison to children with COVID-19 and/or other infections. Children with COVID-19 also exhibited higher frequencies of CD4+ and CD8+ T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen–specific stimulation in comparison to children with other infections. At 6–9 months following treatment and recovery, this enhanced response against SARS-CoV-2 antigens was down modulated in children with MIS.

Conclusion

Our study, therefore, provides evidence of enhanced activation of CD4+ and CD8+ T-cell responses in children with MIS and reversal following recovery.