bluuebunny/crossref_metadata_2025 huggingface dataset:
Interdomain plant–microbe and fungi–bacteria ecological networks under different woodland use intensity during the dry and wet season
Authors: Li Jing , Li Shuaifeng , Huang Xiaobo , Lang Xuedong , Tang Rong , Zhang Rui , Su Jianrong
Published: August 2023

Microbial communities, which are affected by soil types and climate factors, contribute to maintain the function of terrestrial ecosystems. Recent studies have shown that interdomain relationships in below–aboveground communities may contribute greatly to ecosystem functioning. However, the responses of interactions among plant, soil fungal, and bacterial communities to the change of woodland use and their effects on ecosystem multifunctionality (EMF) remain poorly understood. In this study, the plant–microbe and fungi–bacteria interdomain ecology network (IDEN) based on SparCC pairwise associations were constructed by simultaneous aboveground plant surveys and belowground microbial analyses among four different woodland use intensities (WUI) along different seasons. The effects of different seasons on these relationships were surveyed to probe into the links to EMF. With the increase of woodland use intensity, the plant–microbe network complexity decreased, while the fungus–bacteria network complexity increased. In both dry and wet seasons, ecosystem multifunctionality decreased with the increase of woodland use intensity. Some tree species are the network hubs and may play a pivotal role in the community structure stability of the forest ecosystem. During the dry season, WUI could indirectly affect EMF through plant–microbial network complexity. During the wet season, WUI had a direct effect on EMF. WUI also indirectly affected EMF through plant–microbial network complexity and fungus–bacterial network complexity. Air temperature is the main climatic factor for EMF in the dry season, while soil moisture content is the climatic factor for EMF in the wet season. Our study revealed the important role of the relationship between plants and their associated soil microbial communities (IDENs) in maintaining ecosystem processes and function. Investigating the recovery dynamics of inter-domain ecological networks after extreme disturbances is important for understanding the overall development of ecosystems.
Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35
Authors: Cullina Sinead , Wojcik Genevieve L. , Shemirani Ruhollah , Klarin Derek , Gorman Bryan R. , Sorokin Elena P. , Gignoux Christopher R. , Belbin Gillian M. , Pyarajan Saiju , Asgari Samira , Tsao Philip S. , Damrauer Scott M. , Abul-Husn Noura S. , Kenny Eimear E.
Published: August 2023

Peripheral artery disease (PAD) is a form of atherosclerotic cardiovascular disease, affecting ∼8 million Americans, and is known to have racial and ethnic disparities. PAD has been reported to have a significantly higher prevalence in African Americans (AAs) compared to non-Hispanic European Americans (EAs). Hispanic/Latinos (HLs) have been reported to have lower or similar rates of PAD compared to EAs, despite having a paradoxically high burden of PAD risk factors; however, recent work suggests prevalence may differ between sub-groups. Here, we examined a large cohort of diverse adults in the BioMe biobank in New York City. We observed the prevalence of PAD at 1.7% in EAs vs. 8.5% and 9.4% in AAs and HLs, respectively, and among HL sub-groups, the prevalence was found at 11.4% and 11.5% in Puerto Rican and Dominican populations, respectively. Follow-up analysis that adjusted for common risk factors demonstrated that Dominicans had the highest increased risk for PAD relative to EAs [OR = 3.15 (95% CI 2.33–4.25), p < 6.44 × 10−14]. To investigate whether genetic factors may explain this increased risk, we performed admixture mapping by testing the association between local ancestry and PAD in Dominican BioMe participants (N = 1,813) separately from European, African, and Native American (NAT) continental ancestry tracts. The top association with PAD was an NAT ancestry tract at chromosome 2q35 [OR = 1.96 (SE = 0.16), p < 2.75 × 10−05) with 22.6% vs. 12.9% PAD prevalence in heterozygous NAT tract carriers versus non-carriers, respectively. Fine-mapping at this locus implicated tag SNP rs78529201 located within a long intergenic non-coding RNA (lincRNA) LINC00607, a gene expression regulator of key genes related to thrombosis and extracellular remodeling of endothelial cells, suggesting a putative link of the 2q35 locus to PAD etiology. Efforts to reproduce the signal in other Hispanic cohorts were unsuccessful. In summary, we showed how leveraging health system data helped understand nuances of PAD risk across HL sub-groups and admixture mapping approaches elucidated a putative risk locus in a Dominican population.
Intra-cervical lymphatic immunotherapy for dust mite-induced allergic rhinoconjunctivitis in children: a 3-year prospective randomized controlled trial
Authors: Wang Qixing , Wang Kai , Qin Yang , Huang Weijun , Li Yin , Yu Qingqing , Xiong Yu , Guo Yingwei , Zheng Rui , Tang Jun
Published: August 2023

Background

Pediatric allergic rhinoconjunctivitis has become a public concern with an increasing incidence year by year. Conventional subcutaneous immunotherapy (SCIT) has long treatment time, high cost and poor compliance. The novel immunotherapy significantly shortens the course of treatment by directly injecting allergens into cervical lymph nodes, which can perform faster clinical benefits to children.

Objective

By comparing with SCIT, this study aimed to evaluate the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT).

Methods

This is a prospective randomized controlled study. A total of 50 allergic rhinoconjunctivitis children with dust mite allergy was randomly divided into ICLIT group and SCIT group, receiving three cervical intralymphatic injections of dust mite allergen or three years of subcutaneous injection, separately. Primary outcomes included total nasal symptom scores (TNSS), total ocular symptom scores (TOSS), total symptom scores (TSS), total medication scores (TMS), and total quality of life score. Secondary outcomes included pain perception and adverse reactions during treatment. Other secondary outcome was change in Dermatophagoides pteronyssinus (Derp) and Dermatophagoides farina (Derf) -specific IgE level.

Results

Both groups had significantly decreased TNSS, TOSS, TSS, TMS, and total quality of life score after 36 months of treatment (p<0.0001). Compared with SCIT, ICLIT could rapidly improve allergic symptoms (p<0.0001). The short-term efficacy was consistent between the two groups (p=0.07), while the long-term efficacy was better in SCIT group (p<0.0001). The pain perception in ICLIT group was lower than that in SCIT group (p<0.0001). ICLIT group was safer. Specifically, the children had only 3 mild local adverse reactions without systemic adverse reactions. The SCIT group had 14 systemic adverse reactions. At last, the serum Derp and Derf-specific IgE levels in ICLIT and SCIT groups decreased 3 years later (p<0.0001).

Conclusion

ICLIT could ameliorate significantly the allergic symptoms in pediatric patients with an advantage in effectiveness and safety, besides an improved life quality including shortened period of treatment, frequency of drug use and pain perception.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR1800017130.
Homologous versus Heterologous prime-boost COVID-19 Vaccination in autologous hematopoietic stem cell transplantation recipients: a blinded randomized controlled trial
Authors: Sharifi Aliabadi Leyla , Karami Manoochehr , Barkhordar Maryam , Hashemi Nazari Seyed Saeed , Kavousi Amir , Ahmadvand Mohammad , Vaezi Mohammad
Published: August 2023

Background/Purpose

Optimizing vaccine efficacy is of particular concern in patients undergoing hematopoietic stem cell transplantation (HSCT), which mainly have an inadequate immune response to primary SARS-CoV-2 vaccination. This investigation aimed to explore the potential prime-boost COVID-19 vaccination strategies following autologous (auto-) HSCT.

Methods

In a randomized clinical trial, patients who had already received two primary doses of receptor-binding domain (RBD) tetanus toxoid (TT) conjugated SARS-CoV-2 vaccine during three to nine months after auto-HSCT were randomized to receive either a homologous RBD-TT conjugated or heterologous inactivated booster dose four weeks after the primary vaccination course. The primary outcome was comparing the anti-S IgG Immune status ratio (ISR) four weeks after the heterologous versus homologous booster dose. The assessment of safety and reactogenicity adverse events was considered as the secondary outcome.

Results

Sixty-one auto-HSCT recipients were recruited and randomly assigned to receive either homologous or heterologous booster doses four weeks after the primary vaccination course. The mean ISR was 3.40 (95% CI: 2.63- 4.16) before the booster dose with a 90.0% seropositive rate. The ISR raised to 5.12 (95% CI: 4.15- 6.08) with a 100% seropositive rate after heterologous (P= 0.0064) and to 3.42 (95% CI: 2.67- 4.17) with a 93.0% seropositivity after the homologous booster doses (P= 0.96). In addition, the heterologous group suffered more AEs following the booster dosage than the homologous group, but this difference was not statistically significant (p = 0.955). In multivariable analysis, the prime-boost vaccination strategy (heterologous versus homologous), the level of ISR before the booster dose, and the length of time between auto-HSCT and booster dose were the positive predictors of serologic response to a booster dose. No serious adverse event is attributed to booster vaccination.

Conclusion

In patients who were primed with two SARS-CoV-2 vaccine doses during the first year after auto-HSCT, heterologous prime-boost COVID-19 vaccination with inactivated platform resulted in considerably enhanced serologic response and non-significantly higher reactogenicity adverse events than homologous RBD-TT conjugated prime-boost COVID-19 vaccination strategy.
Clinical application of a body area network-based smart bracelet for pre-hospital trauma care
Authors: Han Wei , Yuan Jin-Yang , Li Rui , Yang Le , Fang Jia-Qin , Fan Hao-Jun , Hou Shi-Ke
Published: August 2023

Objective

This study aims to explore the efficiency and effectiveness of a body area network-based smart bracelet for trauma care prior to hospitalization.

Methods

To test the efficacy of the bracelet, an observational cohort study was conducted on the clinical data of 140 trauma patients pre-admission to the hospital. This study was divided into an experimental group receiving smart bracelets and a control group receiving conventional treatment. Both groups were randomized using a random number table. The primary variables of this study were as follows: time to first administration of life-saving intervention, time to first administration of blood transfusion, time to first administration of hemostatic drugs, and mortality rates within 24 h and 28 days post-admission to the hospital. The secondary outcomes included the amount of time before trauma team activation and the overall length of patient stay in the emergency room.

Results

The measurement results for both the emergency smart bracelet as well as traditional equipment showed high levels of consistency and accuracy. In terms of pre-hospital emergency life-saving intervention, there was no significant statistical difference in the mortality rates between both groups within 224 h post-admission to the hospital or after 28-days of treatment in the emergency department. Furthermore, the treatment efficiency for the group of patients wearing smart bracelets was significantly better than that of the control group with regard to both the primary and secondary outcomes of this study. These results indicate that this smart bracelet has the potential to improve the efficiency and effectiveness of trauma care and treatment.

Conclusion

A body area network-based smart bracelet combined with remote 5G technology can assist the administration of emergency care to trauma patients prior to hospital admission, shorten the timeframe in which life-saving interventions are initiated, and allow for a quick trauma team response as well as increased efficiency upon administration of emergency care.
NAFLD and nutraceuticals: a review of completed phase III and IV clinical trials
Authors: Hegazi Omar E. , Alalalmeh Samer O. , Alnuaimi Ghala Rashid Humaid , Shahwan Moyad , Jairoun Ammar Abdulrahman , Alorfi Nasser M. , Majrashi Shaker A. , Alkhanani Mustfa Faisal , Alkhattabi Abdullah , Alourfi Mansour M. , Alsolami Faris A. , Alsharif Saeed , Alshahrani Hatim
Published: August 2023

Background

Nonalcoholic Fatty Liver Disease (NAFLD) has become a significant public health concern, affecting approximately one-fourth of the population. Despite its prevalence, no FDA-approved drug treatments specifically target NAFLD.

Aim

To provide a review of clinical trials investigating the use of herbal remedies and dietary supplements in NAFLD management, utilizing the ClinicalTrials.gov database.

Methods

This review evaluates the current evidence by examining completed phase III and IV clinical trials registered on ClinicalTrials.gov. An exhaustive search was performed on April 17, 2023, using the terms “Nonalcoholic Fatty Liver Disease” and “NAFLD.” Two independent reviewers appraised eligible trials based on pre-defined inclusion and exclusion criteria.

Results

An initial search yielded 1,226 clinical trials, with 12 meeting the inclusion criteria after filtration. The majority of trials focused on Omega-3 fatty acids (20.0%) and vitamin D (26.7%), followed by caffeine, chlorogenic acid, ginger, phosphatidylcholine, Trigonella Foenum-graecum seed extract, vitamin C, and vitamin E (each 6.7%). Most studies were Phase 3 (75.0%) and used a parallel assignment model (91.7%). Quadruple masking was the most prevalent technique (58.3%), and Iran was the leading country in terms of trial locations (25.0%). These interventions constitute two herbal interventions and nine supplement interventions.

Conclusion

This reveals a diverse range of nutraceuticals, with Omega-3 fatty acids and vitamin D being predominant in the management of NAFLD. The global distribution of trials highlights the widespread interest in these therapeutics. However, more rigorous, large-scale trials are needed to establish safety, efficacy, and optimal dosages.
Sub-MIC antibiotics influence the microbiome, resistome and structure of riverine biofilm communities
Authors: Flores-Vargas Gabriela , Korber Darren R. , Bergsveinson Jordyn
Published: August 2023

The effects of sub-minimum inhibitory concentrations (sub-MICs) of antibiotics on aquatic environments is not yet fully understood. Here, we explore these effects by employing a replicated microcosm system fed with river water where biofilm communities were continuously exposed over an eight-week period to sub-MIC exposure (1/10, 1/50, and 1/100 MIC) to a mix of common antibiotics (ciprofloxacin, streptomycin, and oxytetracycline). Biofilms were examined using a structure–function approach entailing microscopy and metagenomic techniques, revealing details on the microbiome, resistome, virulome, and functional prediction. A comparison of three commonly used microbiome and resistome databases was also performed. Differences in biofilm architecture were observed between sub-MIC antibiotic treatments, with an overall reduction of extracellular polymeric substances and autotroph (algal and cyanobacteria) and protozoan biomass, particularly at the 1/10 sub-MIC condition. While metagenomic analyses demonstrated that microbial diversity was lowest at the sub-MIC 1/10 antibiotic treatment, resistome diversity was highest at sub-MIC 1/50. This study also notes the importance of benchmarking analysis tools and careful selection of reference databases, given the disparity in detected antimicrobial resistance genes (ARGs) identity and abundance across methods. Ultimately, the most detected ARGs in sub-MICs exposed biofilms were those that conferred resistance to aminoglycosides, tetracyclines, β-lactams, sulfonamides, and trimethoprim. Co-occurrence of microbiome and resistome features consistently showed a relationship between Proteobacteria genera and aminoglycoside ARGs. Our results support the hypothesis that constant exposure to sub-MICs antibiotics facilitate the transmission and promote prevalence of antibiotic resistance in riverine biofilms communities, and additionally shift overall microbial community metabolic function.
Genetic characteristics and integration specificity of Salmonella enterica temperate phages
Authors: Sun Siqi , Zhang Xianglilan
Published: August 2023

Introduction

Temperate phages can engage in the horizontal transfer of functional genes to their bacterial hosts. Thus, their genetic material becomes an intimate part of bacterial genomes and plays essential roles in bacterial mutation and evolution. Specifically, temperate phages can naturally transmit genes by integrating their genomes into the bacterial host genomes via integrases. Our previous study showed that Salmonella enterica contains the largest number of temperate phages among all publicly available bacterial species. S. enterica is an important pathogen that can cause serious systemic infections and even fatalities.

Methods

Initially, we extracted all S. enterica temperate phages from the extensively developed temperate phage database established in our previous study. Subsequently, we conducted an in-depth analysis of the genetic characteristics and integration specificity exhibited by these S. enterica temperate phages.

Results

Here we identified 8,777 S. enterica temperate phages, all of which have integrases in their genomes. We found 491 non-redundant S. enterica temperate phage integrases (integrase entries). S. enterica temperate phage integrases were classified into three types: intA, intS, and phiRv2. Correlation analysis showed that the sequence lengths of S. enterica integrase and core regions of attB and attP were strongly correlated. Further phylogenetic analysis and taxonomic classification indicated that both the S. enterica temperate phage genomes and the integrase gene sequences were of high diversities.

Discussion

Our work provides insight into the essential integration specificity and genetic diversity of S. enterica temperate phages. This study paves the way for a better understanding of the interactions between phages and S. enterica. By analyzing a large number of S. enterica temperate phages and their integrases, we provide valuable insights into the genetic diversity and prevalence of these elements. This knowledge has important implications for developing targeted therapeutic interventions, such as phage therapy, to combat S. enterica infections. By harnessing the lytic capabilities of temperate phages, they can be engineered or utilized in phage cocktails to specifically target and eradicate S. enterica strains, offering an alternative or complementary approach to traditional antibiotic treatments. Our study has implications for public health and holds potential significance in combating clinical infections caused by S. enterica.
Succession of endophytic fungi and rhizosphere soil fungi and their correlation with secondary metabolites in Fagopyrum dibotrys
Authors: Ma Nan , Yin Dengpan , Liu Ying , Gao Ziyong , Cao Yu , Chen Tongtong , Huang Ziyi , Jia Qiaojun , Wang Dekai
Published: August 2023

Golden buckwheat (Fagopyrum dibotrys, also known as F. acutatum) is a traditional edible herbal medicinal plant with a large number of secondary metabolites and is considered to be a source of therapeutic compounds. Different ecological environments have a significant impact on their compound content and medicinal effects. However, little is known about the interactions between soil physicochemical properties, the rhizosphere, endophytic fungal communities, and secondary metabolites in F. dibotrys. In this study, the rhizosphere soil and endophytic fungal communities of F. dibotrys in five different ecological regions in China were identified based on high-throughput sequencing methods. The correlations between soil physicochemical properties, active components (total saponins, total flavonoids, proanthocyanidin, and epicatechin), and endophytic and rhizosphere soil fungi of F. dibotrys were analyzed. The results showed that soil pH, soil N, OM, and P were significantly correlated with the active components of F. dibotrys. Among them, epicatechin, proanthocyanidin, and total saponins were significantly positively correlated with soil pH, while proanthocyanidin content was significantly positively correlated with STN, SAN, and OM in soil, and total flavone content was significantly positively correlated with P in soil. In soil microbes, Mortierella, Trechispora, Exophiala, Ascomycota_unclassified, Auricularia, Plectosphaerella, Mycena, Fungi_unclassified, Agaricomycetes_unclassified, Coprinellus, and Pseudaleuria were significantly related to key secondary metabolites of F. dibotrys. Diaporthe and Meripilaceae_unclassified were significantly related to key secondary metabolites in the rhizome. This study presents a new opportunity to deeply understand soil-plant-fungal symbioses and secondary metabolites in F. dibotrys, as well as provides a scientific basis for using biological fertilization strategies to improve the quality of F. dibotrys.
Identification and quantitative assessment of motor complications in Parkinson’s disease using the Parkinson’s KinetiGraph™
Authors: Qu Yan , Zhang Tingting , Duo Yunyan , Chen Liling , Li Xiaohong
Published: August 2023

Introduction

Effective management and therapies for the motor complications of Parkinson’s disease (PD) require appropriate clinical evaluation. The Parkinson’s KinetiGraph™ (PKG) is a wearable biosensor system that can record the motion characteristics of PD objectively and remotely.

Objective

The study aims to investigate the value of PKG in identifying and quantitatively assessing motor complications including motor fluctuations and dyskinesia in the Chinese PD population, as well as the correlation with the clinical scale assessments.

Methods

Eighty-four subjects with PD were recruited and continuously wore the PKG for 7 days. Reports with 7-day output data were provided by the manufacturer, including the fluctuation scores (FS) and dyskinesia scores (DKS). Specialists in movement disorders used the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale-IV (MDS-UPDRS IV), the wearing-off questionnaire 9 (WOQ-9), and the unified dyskinesia rating scale (UDysRS) for the clinical assessment of motor complications. Spearman correlation analyses were used to evaluate the correlation between the FS and DKS recorded by the PKG and the clinical scale assessment results. Receiver operating characteristic (ROC) curves were generated to analyze the sensitivity and specificity of the FS and DKS scores in the identification of PD motor complications.

Results

The FS was significantly positively correlated with the MDS-UPDRS IV motor fluctuation (items 4.3–4.5) scores (r = 0.645, p < 0.001). ROC curve analysis showed a maximum FS cut-off value of 7.5 to identify motor fluctuation, with a sensitivity of 74.3% and specificity of 87.8%. The DKS was significantly positively correlated with the UDysRS total score (r = 0.629, p < 0.001) and the UDysRS III score (r = 0.634, p < 0.001). ROC curve analysis showed that the maximum DKS cut-off value for the diagnosis of dyskinesia was 0.7, with a sensitivity of 83.3% and a specificity of 83.3%.

Conclusion

The PKG assessment of motor complications in the PD population analyzed in this study has a significant correlation with the clinical scale assessment, high sensitivity, and high specificity. Compared with clinical evaluations, PKG can objectively, quantitatively, and remotely identify and assess motor complications in PD, providing a good objective recording for managing motor complications.
The thalamic reuniens is associated with consolidation of non-spatial memory too
Authors: Hamilton Jennifer J. , Dalrymple-Alford John C.
Published: August 2023

The nucleus reuniens (RE) is situated in the midline thalamus and provides a key link between the hippocampus and prefrontal cortex. This anatomical relationship positions the Re as an ideal candidate to facilitate memory consolidation. However, there is no evidence that this role extends beyond spatial memory and contextual fear memory, which are both strongly associated with hippocampal function. We, therefore, trained intact male Long–Evans rats on an odor–trace–object paired-associate task where the explicit 10-s delay between paired items renders the task sensitive to hippocampal function. Neurons in the RE showed significantly increased activation of the immediate early gene (Zif268) when rats were re-tested for previous non-spatial memory 25 days after acquisition training, compared to a group tested at 5-days post-acquisition, as well as a control group tested 25 days after acquisition but with a new pair of non-spatial stimuli, and home cage controls. The remote recall group also showed relatively augmented IEG expression in the superficial layers of the medial PFC (anterior cingulate cortex and prelimbic cortex). These findings support the conclusion that the RE is preferentially engaged during remote recall in this non-spatial task and thus has a role beyond spatial memory and contextual fear memory.
Perfusion-weighted software written in Python for DSC-MRI analysis
Authors: Fernández-Rodicio Sabela , Ferro-Costas Gonzalo , Sampedro-Viana Ana , Bazarra-Barreiros Marcos , Ferreirós Alba , López-Arias Esteban , Pérez-Mato María , Ouro Alberto , Pumar José M. , Mosqueira Antonio J. , Alonso-Alonso María Luz , Castillo José , Hervella Pablo , Iglesias-Rey Ramón
Published: August 2023

Introduction

Dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion studies in magnetic resonance imaging (MRI) provide valuable data for studying vascular cerebral pathophysiology in different rodent models of brain diseases (stroke, tumor grading, and neurodegenerative models). The extraction of these hemodynamic parameters via DSC-MRI is based on tracer kinetic modeling, which can be solved using deconvolution-based methods, among others. Most of the post-processing software used in preclinical studies is home-built and custom-designed. Its use being, in most cases, limited to the institution responsible for the development. In this study, we designed a tool that performs the hemodynamic quantification process quickly and in a reliable way for research purposes.

Methods

The DSC-MRI quantification tool, developed as a Python project, performs the basic mathematical steps to generate the parametric maps: cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), signal recovery (SR), and percentage signal recovery (PSR). For the validation process, a data set composed of MRI rat brain scans was evaluated: i) healthy animals, ii) temporal blood–brain barrier (BBB) dysfunction, iii) cerebral chronic hypoperfusion (CCH), iv) ischemic stroke, and v) glioblastoma multiforme (GBM) models. The resulting perfusion parameters were then compared with data retrieved from the literature.

Results

A total of 30 animals were evaluated with our DSC-MRI quantification tool. In all the models, the hemodynamic parameters reported from the literature are reproduced and they are in the same range as our results. The Bland–Altman plot used to describe the agreement between our perfusion quantitative analyses and literature data regarding healthy rats, stroke, and GBM models, determined that the agreement for CBV and MTT is higher than for CBF.

Conclusion

An open-source, Python-based DSC post-processing software package that performs key quantitative perfusion parameters has been developed. Regarding the different animal models used, the results obtained are consistent and in good agreement with the physiological patterns and values reported in the literature. Our development has been built in a modular framework to allow code customization or the addition of alternative algorithms not yet implemented.
Non-canonical pathways in the pathophysiology and therapeutics of bipolar disorder
Authors: Machado-Vieira Rodrigo , Courtes Alan C. , Zarate Carlos A. , Henter Ioline D. , Manji Husseini K.
Published: August 2023

Bipolar disorder (BD) is characterized by extreme mood swings ranging from manic/hypomanic to depressive episodes. The severity, duration, and frequency of these episodes can vary widely between individuals, significantly impacting quality of life. Individuals with BD spend almost half their lives experiencing mood symptoms, especially depression, as well as associated clinical dimensions such as anhedonia, fatigue, suicidality, anxiety, and neurovegetative symptoms. Persistent mood symptoms have been associated with premature mortality, accelerated aging, and elevated prevalence of treatment-resistant depression. Recent efforts have expanded our understanding of the neurobiology of BD and the downstream targets that may help track clinical outcomes and drug development. However, as a polygenic disorder, the neurobiology of BD is complex and involves biological changes in several organelles and downstream targets (pre-, post-, and extra-synaptic), including mitochondrial dysfunction, oxidative stress, altered monoaminergic and glutamatergic systems, lower neurotrophic factor levels, and changes in immune-inflammatory systems. The field has thus moved toward identifying more precise neurobiological targets that, in turn, may help develop personalized approaches and more reliable biomarkers for treatment prediction. Diverse pharmacological and non-pharmacological approaches targeting neurobiological pathways other than neurotransmission have also been tested in mood disorders. This article reviews different neurobiological targets and pathophysiological findings in non-canonical pathways in BD that may offer opportunities to support drug development and identify new, clinically relevant biological mechanisms. These include: neuroinflammation; mitochondrial function; calcium channels; oxidative stress; the glycogen synthase kinase-3 (GSK3) pathway; protein kinase C (PKC); brain-derived neurotrophic factor (BDNF); histone deacetylase (HDAC); and the purinergic signaling pathway.
Vacuum-assisted biopsy system for breast lesions: a potential therapeutic approach
Authors: Zhu Yue , Chen Xingyan , Dou He , Liu Yuqi , Li Fucheng , Wang Youyu , Xiao Min
Published: August 2023

Purpose

The primary objective is to optimize the population eligible for Mammotome Minimally Invasive Surgery (MIS) by refining selection criteria. This involves maximizing procedure benefits, minimizing malignancy risk, and reducing the rate of malignant outcomes.

Patients and methods

A total of 1158 female patients who came to our hospital from November 2016 to August 2021 for the Mammotome MIS were analyzed retrospectively. Following χ2 tests to screen for risk variables, binary logistic regression analysis was used to determine the independent predictors of malignant lesions. In addition, the correlation between age and lesion diameter was investigated for BI-RADS ultrasound (US) category 4a lesions in order to better understand the relationship between these variables.

Results

The malignancy rates of BI-RADS US category 3, category 4a and category 4b patients who underwent the Mammotome MIS were 0.6% (9/1562), 6.4% (37/578) and 8.3% (2/24) respectively. Malignant lesions were more common in patients over the age of 40, have visible blood supply, and BI-RADS category 4 of mammography. In BI-RADS US category 4a lesions, the diameter of malignant tumor was highly correlated with age, and this correlation was strengthened in patients over the age of 40 and with BI-RADS category 4 of mammography.

Conclusion

The results of this study demonstrate that the clinical data and imaging results, particularly age, blood supply, and mammography classification, offer valuable insights to optimize patients’ surgical options and decrease the incidence of malignant outcomes.
Vein of Galen aneurysmal malformation in newborns: a retrospective study to describe a paradigm of treatment and identify risk factors of adverse outcome in a referral center
Authors: Buratti Silvia , Mallamaci Marisa , Tuo Giulia , Severino Mariasavina , Tortora Domenico , Parodi Costanza , Rossi Andrea , Pasetti Francesco , Castellan Lucio , Capra Valeria , Romano Ferruccio , De Marco Patrizia , Pavanello Marco , Piatelli Gianluca , Paladini Dario , Calevo Maria Grazia , Moscatelli Andrea
Published: August 2023

Background

Vein of Galen aneurysmal malformation (VGAM) is a rare cerebral vascular malformation associated with significant morbidity and mortality. Newborns with VGAM without adequate treatment may develop rapidly deteriorating high output heart failure (HOHF) and are at risk for severe neurological outcomes.

Objective

To describe the clinical course and management of newborns with VGAM, and identify which echocardiographic and neuroradiologic factors may be associated with severe heart failure at birth and adverse short term outcomes.

Methods

This is a single center retrospective cohort study including all consecutive newborns with VGAM admitted to Gaslini Children's Hospital between 2009 and 2022. We reviewed clinical data, intensive care support, fetal and neonatal cardiologic and neuroradiologic findings and we studied the association with severe HOHF, endovascular complications and death.

Results

Out of 40 newborns, 17 (42.5%) developed severe HOHF requiring early endovascular procedures. Medical treatment was focused on the main components of HOHF by providing inotropic support and peripheral vasodilation. Pulmonary vasodilators were avoided to reduce the negative effects of pulmonary overflow and prevent vascular remodeling. Reduction of the obligatory left to right shunt through the VGAM was possible only through endovascular treatment. Fetal cardiothoracic ratio was significantly associated with severe HOHF at birth and death. Cardiologic parameters of right ventricular overload, pulmonary hypertension and systemic steal were the leading findings associated with haemodynamic compromise at birth. The mediolateral diameter of the straight or falcine sinus at its shortest section (SS-MD), and arterial pseudofeeders were significantly associated with severe HOHF at birth in prenatal and postnatal assessments. None of the postnatal echocardiographic and MRI variables, nor a higher inotropic support were associated with major periprocedural complications or death. Mortality was due to palliation for congenital severe brain damage (4/40, 10%), or major periprocedural complications (3/40, 7.5%). None of the patients died due to HOHF and multiorgan failure. Overall survival at discharge was 82.5% (33/40).

Conclusions

The complexity of neonatal VGAM pathophysiology requires a multidisciplinary approach, specialized intensive care management, and early endovascular treatment to reduce mortality and optimize clinical outcomes. Cardiologic and neuroradiologic parameters are key to define risk stratification and treatment strategies.
A phase 1 study of dimdazenil to evaluate the pharmacokinetics, food effect and safety in Chinese healthy subjects
Authors: Wang Fei , He Jingjing , Zhou Yanling , Ye Lijun , Li Bei , Ma Zhiyuan , Chen Chunyan , Zhang Ruoxi , Lin Zhaocun , Tang Jinshan , Jin Zhiping , Jiang Yu , Lin Nengming
Published: August 2023

Background and objective: As a partial positive allosteric modulator of the gamma-aminobutyric acid A (GABAA) receptor, dimdazenil was used for the treatment of insomnia with the potential to alleviate associated side effects compared to full agonists. The objective of this trial is to assess the safety, tolerability, food effect and pharmacokinetics following single and multiple doses of dimdazenil in Chinese healthy subjects.

Methods: In this phase 1 trial, 36 healthy subjects aged ≥18 years were assigned to receive a single dose of 1.5, 2.5, or 5 mg dimdazenil, with each dose cohort consisting of 12 subjects, and 14 subjects were assigned to receive a multiple 2.5 mg daily dose of dimdazenil for 5 days. Safety, tolerability, and pharmacokinetic characteristics were evaluated.

Results: Of the 50 subjects enrolled and 49 completed the trial, the incidences of treatment-emergent adverse events (AEs) in the single-dose groups of 1.5, 2.5, and 5 mg were 16.7%, 58.3% and 66.7% respectively, while 61.5% in the multiple-dose group. There were no serious AEs, deaths, AEs leading to discontinuation or AEs of requiring clinical intervention in any treatment groups. The most treatment-emergent AEs were dizziness (n = 4, 8.2%), hyperuricemia (n = 2, 6.1%), upper respiratory tract infection (n = 2, 6.1%), diastolic blood pressure decreased (n = 2, 6.1%), blood TG increased (n = 2, 6.1%) and RBC urine positive (n = 2, 6.1%). All AEs were mild-to-moderate and transient, and no severe AEs were documented in any study phase. The PK profile of dimdazenil and its active metabolite Ro46-1927 was linear across 1.5–5 mg oral doses in humans. The median Tmax for dimdazenil was in the range of 0.5–1.5 h, and the apparent terminal t1/2z ranged from 3.50 to 4.32 h. Taking Dimdazenil with food may delay Tmax and decrease Cmax, without affecting the total exposure (AUC). No relevant accumulations of dimdazenil and Ro 46–1927 were observed in multiple-dose group.

Conclusion: Dimdazenil was generally well tolerated in healthy Chinese subjects after single and 5 days-multiple dosing. The pharmacokinetic properties of dimdazenil are compatible with a drug for the treatment of insomnia.

Clinical Trial Registration: chinadrugtrials.org.cn, identifier CTR20201978
Lineage-specific mutation of Lmx1b provides new insights into distinct regulation of suture development in different areas of the calvaria
Authors: Cabrera Pereira Angel , Dasgupta Krishnakali , Ho Thach-Vu , Pacheco-Vergara Maria , Kim Julie , Kataria Niam , Liang Yaowei , Mei Jeslyn , Yu Jinyeong , Witek Lukasz , Chai Yang , Jeong Juhee
Published: August 2023

The calvaria (top part of the skull) is made of pieces of bone as well as multiple soft tissue joints called sutures. The latter is crucial to the growth and morphogenesis of the skull, and thus a loss of calvarial sutures can lead to severe congenital defects in humans. During embryogenesis, the calvaria develops from the cranial mesenchyme covering the brain, which contains cells originating from the neural crest and the mesoderm. While the mechanism that patterns the cranial mesenchyme into bone and sutures is not well understood, function of Lmx1b, a gene encoding a LIM-domain homeodomain transcription factor, plays a key role in this process. In the current study, we investigated a difference in the function of Lmx1b in different parts of the calvaria using neural crest-specific and mesoderm-specific Lmx1b mutants. We found that Lmx1b was obligatory for development of the interfrontal suture and the anterior fontanel along the dorsal midline of the skull, but not for the posterior fontanel over the midbrain. Also, Lmx1b mutation in the neural crest-derived mesenchyme, but not the mesoderm-derived mesenchyme, had a non-cell autonomous effect on coronal suture development. Furthermore, overexpression of Lmx1b in the neural crest lineage had different effects on the position of the coronal suture on the apical part and the basal part. Other unexpected phenotypes of Lmx1b mutants led to an additional finding that the coronal suture and the sagittal suture are of dual embryonic origin. Together, our data reveal a remarkable level of regional specificity in regulation of calvarial development.
Ecosystem multifunctionality and soil microbial communities in response to ecological restoration in an alpine degraded grassland
Authors: Shu Xiangyang , Liu Weijia , Hu Yufu , Xia Longlong , Fan Kunkun , Zhang Yanyan , Zhang Yulin , Zhou Wei
Published: August 2023

Linkages between microbial communities and multiple ecosystem functions are context-dependent. However, the impacts of different restoration measures on microbial communities and ecosystem functioning remain unclear. Here, a 14-year long-term experiment was conducted using three restoration modes: planting mixed grasses (MG), planting shrub with Salix cupularis alone (SA), and planting shrub with Salix cupularis plus planting mixed grasses (SG), with an extremely degraded grassland serving as the control (CK). Our objective was to investigate how ecosystem multifunctionality and microbial communities (diversity, composition, and co-occurrence networks) respond to different restoration modes. Our results indicated that most of individual functions (i.e., soil nutrient contents, enzyme activities, and microbial biomass) in the SG treatment were significantly higher than in the CK treatment, and even higher than MG and SA treatments. Compared with the CK treatment, treatments MG, SA, and SG significantly increased the multifunctionality index on average by 0.57, 0.23 and 0.76, respectively. Random forest modeling showed that the alpha-diversity and composition of bacterial communities, rather than fungal communities, drove the ecosystem multifunctionality. Moreover, we found that both the MG and SG treatments significantly improved bacterial network stability, which exhabited stronger correlations with ecosystem multifunctionality compared to fungal network stability. In summary, this study demonstrates that planting shrub and grasses altogether is a promising restoration mode that can enhance ecosystem multifunctionality and improve microbial diversity and stability in the alpine degraded grassland.
Crop classification in high-resolution remote sensing images based on multi-scale feature fusion semantic segmentation model
Authors: Lu Tingyu , Gao Meixiang , Wang Lei
Published: August 2023

The great success of deep learning in the field of computer vision provides a development opportunity for intelligent information extraction of remote sensing images. In the field of agriculture, a large number of deep convolutional neural networks have been applied to crop spatial distribution recognition. In this paper, crop mapping is defined as a semantic segmentation problem, and a multi-scale feature fusion semantic segmentation model MSSNet is proposed for crop recognition, aiming at the key problem that multi-scale neural networks can learn multiple features under different sensitivity fields to improve classification accuracy and fine-grained image classification. Firstly, the network uses multi-branch asymmetric convolution and dilated convolution. Each branch concatenates conventional convolution with convolution nuclei of different sizes with dilated convolution with different expansion coefficients. Then, the features extracted from each branch are spliced to achieve multi-scale feature fusion. Finally, a skip connection is used to combine low-level features from the shallow network with abstract features from the deep network to further enrich the semantic information. In the experiment of crop classification using Sentinel-2 remote sensing image, it was found that the method made full use of spectral and spatial characteristics of crop, achieved good recognition effect. The output crop classification mapping was better in plot segmentation and edge characterization of ground objects. This study can provide a good reference for high-precision crop mapping and field plot extraction, and at the same time, avoid excessive data acquisition and processing.
Item response theory approach to ethnocentrism
Authors: Monaghan Conal , Bizumic Boris
Published: August 2023

Introduction

Although ethnocentrism is one of the fundamental concepts in the social sciences, its study has been impeded by a diversity of conceptualizations and measures. In recent years, a growing number of political scientists and psychologists have undertaken in-depth research into ethnocentrism. In addition, researchers have recently proposed a comprehensive reconceptualization of ethnocentrism and developed a new Ethnocentrism scale. There is strong evidence for this scale's reliability and validity in indexing ethnocentrism, but like most measures in psychology and political science, this scale is based on classical test theory. Item response theory (IRT) is a powerful psychometric technique that can provide a much more sophisticated test of test performance and is currently under-utilized in research.

Methods

We performed IRT to assess the psychometric properties of the Ethnocentrism scale on a sample of 4,187 participants.

Results

The scale's items had strong psychometric properties to capture the ethnocentrism latent construct, particularly in the below average to above average range. Men required marginally lower levels of ethnocentrism to endorse less socially acceptable items than women (items relating to superiority, purity, or exploitativeness). When compared to liberals, conservatives responded more readily to nearly all ethnocentrism items. Given this variation, the IRT approach highlighted that future measurements must adjust for differential item functioning, albeit more for political orientation than gender identity.

Discussion

The findings detail how IRT can enhance measurement in political science and demonstrate the implications for how gender and political ideology may affect the differential performance of items.
Problematic smartphone use and sleep disturbance: the roles of metacognitions, desire thinking, and emotion regulation
Authors: Akbari Mehdi , Seydavi Mohammad , Sheikhi Sonay , Spada Marcantonio M.
Published: August 2023

Background

The association between problematic Smartphone use (PSU) and sleep disturbance is evidenced in the literature, but more research is required to investigate the potential factors that may influence the effect of PSU on sleep disturbance. Given the considerable prevalence of PSU (9.3 to 36.7%) and sleep disturbance (55.2%) in Iran, the current study sought to examine an interactional model to test whether metacognitions about Smartphone use, desire thinking (verbal perseveration and imaginal prefiguration), and emotion regulation (expressive suppression and cognitive reappraisal) could have a moderating effect on the above-mentioned association.

Method

This present study is a cross-sectional, observational study that was conducted between June and September 2022 in a convenience sample of Iranians (n = 603, Female = 419, Age = 24.61 ± 8).

Results

Despite the significant association between metacognitions about the Smartphone use, PSU, and sleep disturbance, metacognitions failed to predict sleep disturbance above PSU. A slope analysis showed, however, that a high (not low or moderate) levels of imaginal prefiguration strengthen the association between PSU and sleep disturbance, while a high (not low or moderate) level of cognitive reappraisal and expressive suppression dampen the PSU-sleep disturbance association. We also found that verbal perseveration and expressive suppression were unique predictors of sleep disturbance, while imaginal prefiguration and reappraisal only predicted sleep disturbance if they interacted with PSU.

Conclusion

Theoretically, findings suggest that enhancing cognitive reappraisal (by 1 SD) and reducing imaginal prefiguration (by 1 SD), might protect against sleep disturbance by reducing its association with PSU. Limitations and future directions are discussed.