bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving dual cover crop mixtures to increase shoot biomass production and weed suppression potential
Authors: Groß Jonas , Kümmerer Robin , Heuermann Diana , Gentsch Norman , Schweneker Dörte , Feuerstein Ulf , Guggenberger Georg , von Wirén Nicolaus , Bauer Bernhard
Published: September 2024

Introduction

Cover crop services depend on biomass production and species composition of the cover crop stand. In this study, we investigated the interactions in shoot biomass of dual cover crop mixtures and their competitiveness to suppress weeds before winter under different growing conditions.

Methods

A field experiment was performed on sandy loam soil in Triesdorf, Germany, for two consecutive years. The cover crop species white mustard (Sinapis alba L.), oil radish (Raphanus sativus var. oleiformis L.), phacelia (Phacelia tanacetifolia J.), Egyptian clover (Trifolium alexandrinum L.), common vetch (Vicia sativa L.), field pea (Pisum sativum L.), and field bean (Vicia faba L.) were grown in pure stands or dual mixtures. Cover crops were sown in August, and shoot biomass was harvested at the end of the vegetation period. Cover crop shoot biomass was dried, and the share of each species and the sown test weed (Brassica napus L.) were determined.

Results

The share of shoot biomass of a cover crop species in dual-species mixtures was closely related to its shoot biomass in its pure stand. In both years, mustard and phacelia showed similar interactions in shoot biomass production when growing with a second species. Regarding competitiveness against weeds, cruciferous species outperformed other cover crop species and could suppress weeds even if they were mixed with a less competitive partner. Weed suppression of mixtures with phacelia depended on the second component in the mixture and was more effective in a dry season. Legume species, especially Egyptian clover and common vetch could not suppress weeds in a pure stand.

Discussion

Our results show that species with high weed suppression potential as single stands retain this ability in dual cover crop mixtures, regardless of the suppression potential of the second species that completes the mixture.
Asthma management in the digital age
Authors: Bocian Ilan Y. , Chin Andrew R. , Rodriguez Alyssa , Collins William , Sindher Sayantani B. , Chinthrajah R. Sharon
Published: September 2024

Asthma affects 25 million people in the United States, and its prevalence is increasing. Access to care and adherence to prescribed asthma-treatment programs remain the principal formidable challenges for asthma management. Telemedicine offers substantial opportunities for improved asthma care of patients across the full range of socioeconomic strata. Ever-improving digital tools for asthma assessment and treatment are key components of telemedicine platforms for asthma management. These include a variety of remote patient-monitoring devices, digital inhaler systems, and mobile-health applications that facilitate ongoing assessment and adherence to treatment protocols. Digital tools for monitoring treatment focus on tracking medication use, inhalation technique, and physiological markers such as peak-flow rate and pulse-oximetry. Telemedicine visits allow for elements of assessment via video, approximating or duplicating many aspects of in-person visits, such as evaluating a patient's general appearance, breathing effort, and cough. Challenges remain in ensuring equitable access to these technologies, especially in rural and low-income areas, and in maintaining patient privacy and data security in digital platforms.
Research on design and control methods of a lightweight upper limb joint isokinetic rehabilitation training equipment
Authors: Zhou Zhou , Wan Yuzhu , Su Yingbing , Li Yunwei , Hu Bingshan , Yu Hongliu
Published: September 2024

Introduction

Isokinetic exercise can improve joint muscle strength and stability, making it suitable for early rehabilitation of stroke patients. However, traditional isokinetic equipment is bulky and costly, and cannot effectively avoid external environmental interference.

Methods

This paper designed a lightweight upper limb joint isokinetic rehabilitation training equipment, with a control system that includes a speed planning strategy and speed control with disturbance rejection. Based on the established human-machine kinematic closed-loop model between the equipment and the user, a dynamic evaluation method of torque at the joint level was proposed.

Results

To validate the effectiveness of the equipment, experiments were conducted by manually applying random disturbances to the equipment operated at an isokinetic speed. The results showed that the root mean square error between the observed torque curve of the second-order linear extended state observer used in this paper and the actual disturbance curve was 0.52, and the maximum speed tracking error of the speed control algorithm was 1.27%. In fast and slow sinusoidal speed curve tracking experiments, the root mean square errors of the speed tracking results for this algorithm were 9.65 and 5.27, respectively, while the tracking errors for the PID speed control algorithm under the same environment were 19.94 and 12.11.

Discussion

The research results indicate that compared with traditional PID control method, the proposed control strategy demonstrates superior performance in achieving isokinetic control and suppressing external disturbances, thereby exhibiting significant potential in promoting upper limb rehabilitation among patients.
Rebuilding vascular access: from the viewpoint of mechanics and materials
Authors: Battistella Aurora , Linger Morgan , Nguyen Anh Thy , Madukwe David , Roy-Chaudhury Prabir , Tan Wei
Published: September 2024

This review presents a comprehensive analysis of vascular access in hemodialysis, focusing on the current modalities, their associated challenges, and recent technological advancements. It closely examines the status of three primary types of vascular access: arteriovenous fistulas, arteriovenous grafts, and central venous catheters. The review delves into the complications and pathologies associated with these access types, emphasizing the mechanobiology-related pathogenesis of arteriovenous access. Furthermore, it explores recent clinical trials, biomaterials, and device innovations, highlighting novel pharmaceutical approaches, advanced materials, device designs, and cutting-edge technologies aimed at enhancing the efficacy, safety, and longevity of vascular access in hemodialysis. This synthesis of current knowledge and emerging trends underscores the dynamic evolution of vascular access strategies and their critical role in improving patient care in hemodialysis.
Exploring the barriers and enablers of industrial solutions in renovation projects: a mixed-methods study in the finnish AEC industry
Authors: Chauhan Krishna , Peltokorpi Antti , Lavikka Rita , Seppänen Olli
Published: September 2024

Offsite construction is a major approach to promote industrialisation in construction. However, implementation of prevailing industrial solutions is often less adequate and unsatisfactory, especially in renovation projects. Thus, the overall objective of this study is to understand the reasons behind the poor performance in implementation of the industrial solutions. The specific objectives include identifying the prominent barriers and enablers of prefabricated products in renovation projects. This study employed exploratory sequential mixed method. The qualitative data were gathered via semi-structured interviews to collect experiences and perception of experts related to industrial solutions. This was followed by quantitative data collection via questionnaire survey using a seven-point Likert scale. The major barriers and enablers of industrial solutions in renovation projects have been ranked in this study. The findings reveal that immutability of heritage buildings, the tolerances of old buildings and insufficient spaces to ensure construction work ranked the top three barriers for implementing industrial solutions in renovation projects. Moreover, the study identifies the most significant enablers including shorter project schedules, quality improvement and work safety improvement. The novelty of the research lies in the comprehensive presentation of the barriers and enablers of industrial solutions in the renovation project context. Policymakers, designers, and contractors can utilize these findings as guiding principles to enhance decision-making processes and create viable solutions for the obstacles encountered in renovation projects. This study further represents a vital step towards the efficient and effective implementation of industrial solutions in renovation projects, resulting in more sustainable and cost-effective outcomes.
Performance investigation of a hybrid liquid-desiccant air conditioning system in a pharmaceutical warehouse: a case study and refined strategy
Authors: Huang Li , Guan Bowen , Qi Meiwei , Liu Yanbin , Yang Haobo
Published: September 2024

Liquid-desiccant-based air conditioning demonstrates significant potential for energy conservation and emission reduction in industrial building applications, contributing to the advancement of a cleaner industrial future. In this study, the on-site performance of a hybrid liquid-desiccant air conditioning system installed in a pharmaceutical warehouse was assessed. The results revealed that blind use of the liquid desiccant caused considerable heat–cold offset in the system, which badly restricted its energy performance. Under the basic conditions, only 81.8% of the total cooling capacity provided by the system could be obtained through the return air, while the remaining 18.2% was wasted owing to the considerable heat–cold offset. A refined system was then proposed to improve the system energy performance. By avoiding the heat–cold offset, the coefficient of performance could be improved from 2.2–2.4 to 2.9–3.1. Moreover, an electricity savings rate of 20.2% was achieved with the refined system over the duration of the entire cooling season. Hence, this work provides valuable insights into energy conservation and emission reduction in industrial air conditioning systems, supporting the process of industrial decarbonization.
Effects of platelet-rich fibrin on human endometrial stromal cells behavior in comparison to platelet-rich plasma
Authors: Yuan Guanghui , Li Duan , Du Xin , Liu Yingxue , Wang Xiaoxiao , Hao Cuifang
Published: September 2024

Introduction

Intrauterine transfusion of platelet-rich plasma (PRP) has become a new treatment for thin endometrium (TE) in recent years, but its low efficacy due to rapid release of growth factors limits its clinical use. Platelet-rich fibrin (PRF) starts the coagulation cascade reaction immediately after the blood comes into contact with the test tube. The natural coagulation process results in stable platelet activation and the slow release of growth factors.

Methods

In our study, primary human endometrial stromal cells (hESCs) were extracted from endometrial tissue. PRP and PRF were prepared from the patient cubital vein blood. Stromal cells were cultured in conditioned medium supplemented with PRP and PRF. Differences in cell behavior were observed by cell proliferation test and cell migration test. The relative expression levels of apoptotic Bax and antiapoptotic Bcl-2 genes were measured by qRT-PCR. The release of growth factors from PRP and PRF was detected by ELISA.

Results

We found that both PRP and PRF inhibited apoptosis of hESCs, which favored cell proliferation and migration. In addition, PRF releases growth factors for a longer period of time compared to PRP.

Discussion

PRF offer a more sustained therapeutic effect compared to PRP, which provides a new idea for endometrial regeneration and repair.
Determinants of small-scale irrigation adoption in drought-prone areas of northcentral Ethiopia in the context of climate change
Authors: Asfaw Eshetu Amogne , Mekonen Abebe Arega
Published: September 2024

Introduction

One feasible way to prepare for the adverse effects of climate change in rainfed-dependent livelihood zones is through irrigation. This study examines small-scale irrigation practices and their determinants.

Methods

Using structured survey questionnaires, interviews, and field observations, we used a cross-sectional survey design to collect data from 380 randomly selected households. The data analysis involved percentages, problem confrontation index, Chi-square test, independent samples t-test, and binary logistic regression model.

Results

The findings revealed that river/stream diversion (40%), using nearby springs (19%), and hand-dug walls (18%) were the predominant types of irrigation. At the same time, water scarcity (PCI = 743), land shortage (PCI = 345), and labor (PCI = 212) were the main impediments to irrigation practices. The binary logistic regression model revealed educational status (OR = 1.239, p < 0.05), headship type (OR = 0.246, p < 0.05), age (OR = 0.943, p < 0.05), relative agroecological location (OR = 7.605; 13.929, p < 0.05), family size (OR = 1.936, p < 0.05), land size (OR = 8.609, p < 0.05), responsibility (OR = 2.069, p < 0.05), and crop failure (OR = 0.389, p < 0.05) as factors affecting the adoption of small-scale irrigation.

Discussion

We recommend offering financial assistance to farmers with limited resources to acquire and install labor- and water-saving irrigation systems. Training and extension services on operating and maintaining small-scale irrigation technologies should be provided. Timely information sharing is also necessary to increase the use of irrigation on a small scale as a feasible adaptation to climate change.
Effectiveness analysis of deceleration capacity and traditional heart rate variability in diagnosing vasovagal syncope
Authors: Guo Yongzhe , Lin Tao , Lin Nanyu , Lin Huizhong
Published: September 2024

Background

Vasovagal syncope (VVS) is a prevalent medical condition with a lack of efficient methods for its detection.

Aim

This study aimed to explore an objective clinical indicator in diagnosing VVS.

Methods

The retrospective analysis involved clinical data of 243 syncope patients from 1 June 2020 to 31 July 2023. Among them, 108 patients had a negative result in the tilt test (TTT), while the remaining 135 patients had a positive result in the TTT. Relevant statistical methods were utilized to examine the correlation between VVS and different indicators of heart rate variability.

Results

After screening, 354 patients being considered for VVS were evaluated, resulting in a final sample size of 243. Sex, age, deceleration capacity (DC), and standard deviation of all normal-to-normal intervals (SDNNs) were the variables that showed statistical significance between the TTT(−) group and the TTT(+) group. Independent risk factors identified by multivariate logistic regression were DC [odds ratio (OR) 1.710, 95% confidence interval (CI) 1.388–2.106, P < 0.001] and SDNN (OR 1.033, 95% CI 1.018–1.049, P < 0.001). Comparing the groups, receiver operating characteristic analysis revealed a notable distinction in both DC and SDNN [the respective areas under the curve were 0.789 (95% CI 0.730–0.848) and 0.702 (95% CI 0.637–0.767); the cutoff values were 7.15 and 131.42; P < 0.001, respectively].

Conclusion

In summary, DC can function as an impartial and easily accessible clinical marker for differentiating VVS. A value exceeding 7.15 ms might suggest a higher likelihood of syncope.
Coil-assisted ethanol embolization of traumatic arteriovenous fistulas: a 10-year retrospective study
Authors: Shen Yuchen , Han Qianyun , Wang Deming , Su Lixin , Wen Mingzhe , Fan Xindong , Yang Xitao
Published: September 2024

Purpose

This study aimed to evaluate the efficacy and safety of ethanol embolization in treating traumatic arteriovenous fistulas (TAVFs).

Materials and methods

From March 2012 to April 2020, 42 consecutive patients (29.9 ± 15.1 years, range: 3–68 years) with peripheral TAVFs underwent ethanol embolization. All patients underwent clinical and imaging follow-ups (40.0 ± 25.9 months, range: 3–90 months). The mean time to onset of symptoms after trauma was 5.4 ± 5.9 months (range: 0.5–30 months). Among the patients, 27 (64.3%) reported that the TAVFs occurred after blunt trauma, 10 (23.8%) presented after penetrating trauma (with 4 patients involving penetration by infusion indwelling needles), and 3 (7.1%) had a history of surgery. Treatment effects, devascularization rates, and complications were evaluated at follow-ups conducted at 1–3 month intervals.

Results

Seventy-one embolization procedures were performed, with a mean of 1.6 ± 0.7 procedures per patient. Thirty-four patients received coil-assisted ethanol embolization. Absolute ethanol was used in all procedures, with an average volume of 7.1 ± 4.2 ml per procedure (range: 1–18 ml); 28 patients (28/42, 66.7%) received coil embolization in 36 procedures (36/71, 50.7%). Upon re-examination, 39 patients (92.9%) achieved 100% devascularization; of these, 29 patients (74.4%) with Schobinger stage II TAVFs improved to stage I or became asymptomatic. Overall, 30 cases (66.7%) achieved a complete response, while the other 12 cases (33.3%) showed a partial response. In addition, no major complications were observed postoperatively, apart from minor complications.

Conclusions

Coil-assisted ethanol embolization can effectively manage TAVFs with an acceptable risk of mild complications.
Angiogenic factor-driven improvement of refractory thin endometrium with autologous platelet-rich plasma intrauterine infusion in frozen embryo transfer cycles
Authors: Shin So Yeon , Chung Nanum , Shin Ji Eun , Kim Jee Hyun , Park Chan , Kwon Hwang , Choi Dong Hee , Lee Jung Ryeol , Kim Ji Hyang
Published: September 2024

Objective

A beneficial effect on endometrial thickness (EMT) and improvement of pregnancy outcome after intrauterine infusion of platelet-rich plasma (PRP) has been suggested. This study assessed the effect of intrauterine PRP infusion on live birth rate and obstetrical outcomes and analyzed cytokines that can potentially improve pregnancy outcomes through PRP.

Method

This study was a prospective cohort study conducted in a university hospital fertility center. The study included ninety-one patients who had a history of two or more failed in vitro fertilization (IVF) attempts and refractory thin endometrium that remained unresponsive after at least two conventional treatments for thin endometrium. Patients were treated with an intrauterine infusion of autologous PRP between days 7 and 14 of their hormone replacement therapy-frozen embryo transfer (HRT-FET) cycle. PRP was administered at 3-day intervals until their EMT reached 7mm. After a maximum of three PRP administrations, embryo transfer (ET) was performed. The primary outcome was the live birth rate. Secondary outcomes included the implantation rate and increase in EMT compared to the previous cycle. We compared the cytokines related to angiogenesis in a patient’s whole blood (WB) and PRP by utilizing a commercial screening kit.

Results

The live birth rate in the PRP treatment cycle was 20.9% (19 of 91 patients), significantly superior to the previous cycle without PRP infusion (p < 0.001). The implantation rate was also significantly higher during the PRP treatment cycle (16.4%) compared to the previous cycle (3.1%) (p < 0.001). The mean EMT post-PRP treatment was 6.1 mm, showing a significant increase of 0.8 mm (p < 0.001). Nonetheless, an increase in EMT was also observed in the non-pregnancy group. No adverse effects were reported by patients treated with autologous PRP. Cytokine array analysis confirmed marked increases in well-known pro-angiogenic factors such as Ang-1, EGF, LAP (TGF-b1), MMP-8, PDGF-AA, and PDGF-AB/PDGF-BB.

Conclusion

Intrauterine PRP infusion offers a safe and effective treatment for patients with refractory thin endometrium and implantation failures. The angiogenic cytokines present in PRP are the primary drivers of this improvement.
Navigating the fungal battlefield: cysteine-rich antifungal proteins and peptides from Eurotiales
Authors: Holzknecht Jeanett , Marx Florentine
Published: September 2024

Fungi are ubiquitous in the environment and play a key role in the decomposition and recycling of nutrients. On the one hand, their special properties are a great asset for the agricultural and industrial sector, as they are used as source of nutrients, producers of enzymes, pigments, flavorings, and biocontrol agents, and in food processing, bio-remediation and plant growth promotion. On the other hand, they pose a serious challenge to our lives and the environment, as they are responsible for fungal infections in plants, animals and humans. Although host immunity opposes invading pathogens, certain factors favor the manifestation of fungal diseases. The prevalence of fungal infections is on the rise, and there is an alarming increase in the resistance of fungal pathogens to approved drugs. The limited number of antimycotics, the obstacles encountered in the development of new drugs due to the poor tolerability of antifungal agents in patients, the limited number of unique antifungal targets, and the low species specificity contribute to the gradual depletion of the antifungal pipeline and newly discovered antifungal drugs are rare. Promising candidates as next-generation therapeutics are antimicrobial proteins and peptides (AMPs) produced by numerous prokaryotic and eukaryotic organisms belonging to all kingdom classes. Importantly, filamentous fungi from the order Eurotiales have been shown to be a rich source of AMPs with specific antifungal activity. A growing number of published studies reflects the efforts made in the search for new antifungal proteins and peptides (AFPs), their efficacy, species specificity and applicability. In this review, we discuss important aspects related to fungi, their impact on our life and issues involved in treating fungal infections in plants, animals and humans. We specifically highlight the potential of AFPs from Eurotiales as promising alternative antifungal therapeutics. This article provides insight into the structural features, mode of action, and progress made toward their potential application in a clinical and agricultural setting. It also identifies the challenges that must be overcome in order to develop AFPs into therapeutics.
mtPCDI: a machine learning-based prognostic model for prostate cancer recurrence
Authors: Cheng Guoliang , Xu Junrong , Wang Honghua , Chen Jingzhao , Huang Liwei , Qian Zhi Rong , Fan Yong
Published: September 2024

Background

This research seeks to formulate a prognostic model for forecasting prostate cancer recurrence by examining the interaction between mitochondrial function and programmed cell death (PCD).

Methods

The research involved analyzing four gene expression datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) using univariate Cox regression. These analyses identified genes linked with mitochondrial function and PCD that correlate with recurrence prognosis. Various machine learning algorithms were then employed to construct an optimal predictive model.

Results

A key outcome was the creation of a mitochondrial-related programmed cell death index (mtPCDI), which effectively predicts the prognosis of prostate cancer patients. It was observed that individuals with lower mtPCDI exhibited higher immune activity, correlating with better recurrence outcomes.

Conclusion

The study demonstrates that mtPCDI can be used for personalized risk assessment and therapeutic decision-making, highlighting its clinical significance and providing insights into the biological processes affecting prostate cancer recurrence.
Variation of tRNA modifications with and without intron dependency
Authors: Hayashi Sachiko
Published: September 2024

tRNAs have recently gained attention for their novel regulatory roles in translation and for their diverse functions beyond translation. One of the most remarkable aspects of tRNA biogenesis is the incorporation of various chemical modifications, ranging from simple base or ribose methylation to more complex hypermodifications such as formation of queuosine and wybutosine. Some tRNAs are transcribed as intron-containing pre-tRNAs. While the majority of these modifications occur independently of introns, some are catalyzed in an intron-inhibitory manner, and in certain cases, they occur in an intron-dependent manner. This review focuses on pre-tRNA modification, including intron-containing pre-tRNA, in both intron-inhibitory and intron-dependent fashions. Any perturbations in the modification and processing of tRNAs may lead to a range of diseases and disorders, highlighting the importance of understanding these mechanisms in molecular biology and medicine.
Detection, isolation and characterization of phage-host complexes using BONCAT and click chemistry
Authors: Hellwig Patrick , Dittrich Anna , Heyer Robert , Reichl Udo , Benndorf Dirk
Published: September 2024

Introduction

Phages are viruses that infect prokaryotes and can shape microbial communities by lysis, thus offering applications in various fields. However, challenges exist in sampling, isolation and accurate prediction of the host specificity of phages as well as in the identification of newly replicated virions in response to environmental challenges.

Methods

A new workflow using biorthogonal non-canonical amino acid tagging (BONCAT) and click chemistry (CC) allowed the combined analysis of phages and their hosts, the identification of newly replicated virions, and the specific tagging of phages with biotin for affinity chromatography.

Results

Replication of phage λ in Escherichia coli was selected as a model for workflow development. Specific labeling of phage λ proteins with the non-canonical amino acid 4-azido-L-homoalanine (AHA) during phage development in E. coli was confirmed by LC–MS/MS. Subsequent tagging of AHA with fluorescent dyes via CC allowed the visualization of phages adsorbed to the cell surface by fluorescence microscopy. Flow cytometry enabled the automated detection of these fluorescent phage-host complexes. Alternatively, AHA-labeled phages were tagged with biotin for purification by affinity chromatography. Despite biotinylation the tagged phages could be purified and were infectious after purification.

Discussion

Applying this approach to environmental samples would enable host screening without cultivation. A flexible and powerful workflow for the detection and enrichment of phages and their hosts in pure cultures has been established. The developed method lays the groundwork for future workflows that could enable the isolation of phage-host complexes from diverse complex microbial communities using fluorescence-activated cell sorting or biotin purification. The ability to expand and customize the workflow through the growing range of compounds for CC offers the potential to develop a versatile toolbox in phage research. This work provides a starting point for these further studies by providing a comprehensive standard operating procedure.
New insights into the structure and function of microbial communities in Maxwell Bay, Antarctica
Authors: Wang Zheng , Gao Zhiwei , Yu Yong , Li Huirong , Luo Wei , Ji Zhongqiang , Ding Haitao
Published: September 2024

The microbial communities inhabiting polar ecosystems, particularly in Maxwell Bay, Antarctica, play a pivotal role in nutrient cycling and ecosystem dynamics. However, the diversity of these microbial communities remains underexplored. In this study, we aim to address this gap by investigating the distribution, environmental drivers, and metabolic potential of microorganisms in Maxwell Bay. We analyzed the prokaryotic and eukaryotic microbiota at 11 stations, revealing distinctive community structures and diverse phylum dominance by using high-throughput sequencing. Spatial analysis revealed a significant impact of longitude on microbial communities, with microeukaryotes exhibiting greater sensitivity to spatial factors than microprokaryotes. We constructed co-occurrence networks to explore the stability of microbial communities, indicating the complexity and stability of microprokaryotic communities compared with those of microeukaryotes. Our findings suggest that the microeukaryotic communities in Maxwell Bay are more susceptible to disturbances. Additionally, this study revealed the spatial correlations between microbial communities, diversity, and environmental variables. Redundancy analysis highlighted the significance of pH and dissolved oxygen in shaping microprokaryotic and microeukaryotic communities, indicating the anthropogenic influence near the scientific research stations. Functional predictions using Tax4Fun2 and FUNGuild revealed the metabolic potential and trophic modes of the microprokaryotic and microeukaryotic communities, respectively. Finally, this study provides novel insights into the microbial ecology of Maxwell Bay, expanding the understanding of polar microbiomes and their responses to environmental factors.
Automated brain segmentation and volumetry in dementia diagnostics: a narrative review with emphasis on FreeSurfer
Authors: Khadhraoui Eya , Nickl-Jockschat Thomas , Henkes Hans , Behme Daniel , Müller Sebastian Johannes
Published: September 2024

Background

Dementia can be caused by numerous different diseases that present variable clinical courses and reveal multiple patterns of brain atrophy, making its accurate early diagnosis by conventional examinative means challenging. Although highly accurate and powerful, magnetic resonance imaging (MRI) currently plays only a supportive role in dementia diagnosis, largely due to the enormous volume and diversity of data it generates. AI-based software solutions/algorithms that can perform automated segmentation and volumetry analyses of MRI data are being increasingly used to address this issue. Numerous commercial and non-commercial software solutions for automated brain segmentation and volumetry exist, with FreeSurfer being the most frequently used.

Objectives

This Review is an account of the current situation regarding the application of automated brain segmentation and volumetry to dementia diagnosis.

Methods

We performed a PubMed search for “FreeSurfer AND Dementia” and obtained 493 results. Based on these search results, we conducted an in-depth source analysis to identify additional publications, software tools, and methods. Studies were analyzed for design, patient collective, and for statistical evaluation (mathematical methods, correlations).

Results

In the studies identified, the main diseases and cohorts represented were Alzheimer’s disease (n = 276), mild cognitive impairment (n = 157), frontotemporal dementia (n = 34), Parkinson’s disease (n = 29), dementia with Lewy bodies (n = 20), and healthy controls (n = 356). The findings and methods of a selection of the studies identified were summarized and discussed.

Conclusion

Our evaluation showed that, while a large number of studies and software solutions are available, many diseases are underrepresented in terms of their incidence. There is therefore plenty of scope for targeted research.
Polarized benzene rings can promote the interaction between CaM and the CaMBD region of nNOS
Authors: Wan Wei , Wang Nan
Published: September 2024

Introduction

The neuronal nitric oxide synthase (nNOS) subtype of nitric oxide synthase (NOS) is an enzyme required for learning and memory. Overactivation of nNOS can lead to oxidative/nitrite stress, which is complicit in the pathophysiology of various neurological and psychiatric disorders. Previous studies have shown that calmodulin (CaM) forms complexes with Ca2+ and binds to the calmodulin-binding domain (CaMBD) of nNOS, thereby upregulating its catalytic activity in hippocampal neurons. To date, there has been no explanation for the non-covalent interactions in the CaMBD-CaM binding structure model of nNOS.

Methods

In this study, we aimed to investigate the intrinsic factors involved in the binding of CaM to NOS-CaMBD and designed interfering peptides based on the N0 peptide structure of the original nNOS-CaMBD sequence: N1 (obtained from the L734F mutation), N2 (obtained from the F731Y and F740Y mutations), and N3 (obtained from the F731L, V738L, and F740L mutations). We employed homology modeling to construct six CaM-peptide complex models, aiming to elucidate the roles of key amino acid residues within the N0 peptide in its interaction with CaM by means of molecular dynamics simulations. The effect of the peptides on the activation and release of NO by nNOS in neurons was assessed using murine primary neuronal cells.

Results

When measuring neuronal NO content, it was found that adding N2 and N3 to cultivated neurons significantly increased nNOS activity, leading to the increased NO production. We found that interfering peptides could stably bind to CaM. Among them, N2 and CaM exhibited the strongest binding ability, indicating that the polarized benzene ring significantly enhanced the binding between nNOS-CaMBD and CaM. Conversely, the binding ability between N0 and CaM was the weakest, as they exhibited the worst polar contact, weakest hydrogen bonding, and the lowest binding free energy. The simulation results also highlighted several important amino acid residues: The K76 of CaM plays an important role in polar contact and hydrogen bonding formation, the L734 residue suppressed model flexibility to a certain extent and had an adverse effect on the overall binding free energy of the model. These results, compared with the results of cellular NO content, a preliminary verification of the antagonistic competitive mechanism between CaM allosteric activation of nNOS and SUMOylation hyperactivation was performed.

Discussion

In summary, this study explored the ability and mode of action of key residues in nNOS-CaMBD on the binding of interfering peptides to CaM, thereby providing new structural perspectives for the activation of nNOS by CaM and recommendations for drug design targeting the specific inhibition of nNOS.
Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial
Authors: Lin Chu-hui , Zeng Ting , Lu Cui-wei , Li De-yang , Liu Yi-ying , Li Bing-mei , Chen Sheng-qiang , Deng Yu-hong
Published: September 2024

Background

The clinical utility of Bacteroides fragilis in treating autism spectrum disorder (ASD) remains unclear. Therefore, this randomized, double-blind, placebo-controlled study aimed to explore the therapeutic effects and safety of B. fragilis BF839 in the treatment of pediatric ASD.

Methods

We examined 60 children aged 2–10 years diagnosed with ASD, and participants received either BF839 powder (10 g/bar with ≥106 CFU/bar of viable bacteria, two bars/day) or placebo for 16 weeks. The primary outcomes was Autism Behavior Checklist (ABC) score. The secondary outcomes were Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Normal Development of Social Skills from Infants to Junior High School Children (S-M), Gastrointestinal Symptom Rating Scale (GSRS) scores, and fecal microbiome composition. Assessments were performed on day 0 and at weeks 8 and 16.

Results

Compared with the placebo group, the BF839 group showed significant improvement in the ABC body and object use scores at week 16, which was more pronounced in children with ASD aged <4 years. Among children with a baseline CARS score ≥30, the BF839 group showed significant improvements at week 16 in the ABC total score, ABC body and object use score, CARS score, and GSRS score compared to the placebo group. Only two patients (6.67%) in the BF839 group experienced mild diarrhea. Compared with baseline and placebo group levels, the BF839 group showed a significant post-intervention increase in abundance of bifidobacteria and change in the metabolic function of neuroactive compounds encoded by intestinal microorganisms.

Conclusion

BF839 significantly and safely improved abnormal behavior and gastrointestinal symptoms in children with ASD.
Case report: Germline BRCA 2 mutation in primary peritoneal carcinoma: a rare malignancy
Authors: Huang Yan-Ying , Zhang Yue , Xie Wen-Jun , Li Zhao-Dong
Published: September 2024

Background

Primary peritoneal carcinoma (PPC) is a rare malignancy. Clinically, its histological morphology resembles that of epithelial ovarian tumors (EOC), often leading to misdiagnosis. Diagnosis and treatment of PPC are time-sensitive because of the rapidly progressive nature of the disease.

Case report

Herein, we report the case of a 54-year-old woman who was initially diagnosed with ovarian cancer; however, extensive workup showed evidence of Müllerian PPC origin. Furthermore, the patient harbored a targetable BRCA mutation.

Conclusion

The patient was treated with the BRCA-targeting agents and had a good prognosis after surgery.
PFKFB3 deprivation attenuates the cisplatin resistance via blocking its autophagic elimination in colorectal cancer cells
Authors: Li Qianqian , Ma Jianxing , Zhang Yaqin , Sun Fengyao , Li Wen , Shen Wenzhi , Ai Zhiying , Li Changli , Wang Shanshan , Wei Xiaonan , Yan Siyuan
Published: September 2024

Introduction

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is highly expressed in several cancers and plays important roles during the whole pathological process of cancer. It is also involved in chemoresistance, while the intrinsic mechanism needs to be further revealed.

Methods

The different responses to cisplatin (DDP) between wild type (WT) and DDP-resistant (DDR) colorectal cancer (CRC) cells were analyzed by several assays. Coumarin conjugated DDP (CP-DDP) was utilized to trace the distribution of DDP. Pharmacological and genetic methods were used to deprive autophagy and PFKFB3, and the effects were investigated. The mouse xenograft model was performed to confirm the effect of the PFKFB3 inhibitor on reversing DDP resistance.

Results

DDR cells showed a lower capacity for apoptosis upon DDP treatment, but exhibited higher levels of autophagy and PFKFB3. CP-DDP partly co-localized with LC3, and its content lessened faster in DDR cells. Deprivation of both autophagy and PFKFB3 attenuated CP-DDP elimination, and reversed the DDP resistance. Moreover, PFKFB3 inhibition reduced DDP-induced autophagy. PFKFB3 inhibitor in combination with DDP led to a remarkable reduction in tumor growth in vivo.

Discussions

Inhibition of PFKFB3 reduced the autophagy induced by DDP, and therefore extended the retention time of CP-DDP. Meanwhile, PFKFB3 deprivation reversed the DDP resistance and made it a potent therapeutic target for CRC.
Liquiritin ameliorates painful diabetic neuropathy in SD rats by inhibiting NLRP3-MMP-9-mediated reversal of aquaporin-4 polarity in the glymphatic system
Authors: Jia Shuai-Ying , Yin Wen-Qin , Xu Wen-Mei , Li Jiang , Yan Wei , Lin Jing-Yan
Published: September 2024

Background

Despite advancements in diabetes treatment, the management of Painful Diabetic Neuropathy (PDN) remains challenging. Our previous research indicated a significant correlation between the expression and distribution of Aquaporin-4 (AQP4) in the spinal glymphatic system and PDN. However, the potential role and mechanism of liquiritin in PDN treatment remain uncertain.

Methods

This study established a rat model of PDN using a combination of low-dose Streptozotocin (STZ) and a high-fat, high-sugar diet. Rats were treated with liquiritin and MCC950 (an NLRP3 inhibitor). We monitored fasting blood glucose, body weight, and mechanical allodynia periodically. The glymphatic system’s clearance function was evaluated using Magnetic Resonance Imaging (MRI), and changes in proteins including NLRP3, MMP-9, and AQP4 were detected through immunofluorescence and Western blot techniques.

Results

The rats with painful diabetic neuropathy (PDN) demonstrated several physiological changes, including heightened mechanical allodynia, compromised clearance function within the spinal glymphatic system, altered distribution of AQP4, increased count of activated astrocytes, elevated expression levels of NLRP3 and MMP-9, and decreased expression of AQP4. However, following treatment with liquiritin and MCC950, these rats exhibited notable improvements.

Conclusion

Liquiritin may promote the restoration of AQP4 polarity by inhibiting NLRP3 and MMP-9, thereby enhancing the clearance functions of the spinal cord glymphatic system in PDN rats, alleviating the progression of PDN.
Paulownin elicits anti-tumor effects by enhancing NK cell cytotoxicity through JNK pathway activation
Authors: Park Eun Sun , Hwang Yo Sep , Ryu Hyung Won , Yoon Hyang Ran , Kim Jong-Tae , Lim Jong-Seok , Cho Hee Jun , Lee Hee Gu
Published: September 2024

Paulownin, a natural compound derived from Paulownia tomentosa wood, exhibits various physiological functions, including anti-bacterial and anti-fungal effects. However, the impact of paulownin on natural killer (NK) cell immune activity remains largely unknown. In this study, we investigated the effect of paulownin on NK cell activity both in vitro and in vivo, and explored its potential mechanisms. NK-92 cells were used for in vitro experiments and a BALB/c mouse model with B16F10 cells injected subcutaneously were used for in vivo anti-tumor analysis. We found that paulownin enhanced the cytolytic activity of NK-92 cells against leukemia, human colon, and human lung cancer cell lines. Paulownin treatment increased the expression of the degranulation marker protein CD107a and cytolytic granules, including granzyme B and perforin in NK-92 cells. Moreover, these enhancements of cytotoxicity and the expression of cytolytic granules induced by paulownin were also observed in human primary NK cells. Signaling studies showed that paulownin promoted the phosphorylation of JNK. The increased perforin expression and elevated cytotoxic activity induced by paulownin were effectively inhibited by pre-treatment with a JNK inhibitor. In vivo studies demonstrated that the administration of paulownin suppressed the growth of B16F10 melanoma cells allografted into mice. Paulownin administration promoted the activation of NK cells in the spleen of mice, resulting in enhanced cytotoxicity against YAC-1 cells. Moreover, the anti-tumor effects of paulownin were reduced upon the depletion of NK cells. Therefore, these results suggest that paulownin enhances NK cell cytotoxicity by activating the JNK signaling pathway and provide significant implications for developing new strategies for cancer immunotherapy.
Drug-drug interaction between diltiazem and tacrolimus in relation to CYP3A5 genotype status in Chinese pediatric patients with nephrotic range proteinuria: a retrospective study
Authors: Yang Qiaoling , Wang Yan , Wang Xuebin , Wang Ping , Tan Boyu , Li Yijun , Sun Huajun , Huang Wenyan , Liu Hongxia
Published: September 2024

Background

Tacrolimus is widely used to treat pediatric nephrotic range proteinuria (NRP). Diltiazem, a CYP3A4/5 inhibitor, is often administered with tacrolimus, affecting its pharmacokinetic profile. The impact of this combination on tacrolimus exposure, particularly in CYP3A5*3 genetic polymorphism, remains unclear in pediatric NRP patients. This study aimed to evaluate the effects of diltiazem on tacrolimus pharmacokinetics, focusing on the CYP3A5*3 polymorphism.

Methods

We conducted a retrospective clinical study involving pediatric NRP patients, divided into two groups: those receiving tacrolimus with diltiazem and those receiving tacrolimus alone. Propensity score matching (PSM) was used to balance the baseline characteristics between the groups. We compared daily dose-adjusted trough concentrations (C0/D) of tacrolimus in both the original and PSM cohorts. The influence of diltiazem on tacrolimus C0/D, stratified by CYP3A5*3 genetic polymorphism, was assessed in a self-controlled case series study.

Results

Before PSM, the tacrolimus C0/D in patients taking diltiazem was significantly higher compared to those with tacrolimus alone (75.84 vs. 56.86 ng/mL per mg/kg, P = 0.034). This finding persisted after PSM (75.84 vs. 46.93 ng/mL per mg/kg, P= 0.028). In the self-controlled case study, tacrolimus C0/D elevated about twofold (75.84 vs. 34.76 ng/mL per mg/kg, P < 0.001) after diltiazem administration. CYP3A5 expressers (CYP3A5*1/*1 and *1/*3) and CYP3A5 non-expressers (CYP3A5*3/*3) experienced a 1.8-fold and 1.3-fold increase in tacrolimus C0/D when combined with diltiazem, respectively.

Conclusion

Diltiazem significantly increased tacrolimus C0/D, with CYP3A5*3 expressers showing higher elevations than non-expressers among pediatric NRP patients. These findings highlight the importance of personalized tacrolimus therapy based on CYP3A5*3 genotypes in pediatric patients taking diltiazem.
A new perspective on the regulation of glucose and cholesterol transport by mitochondria-lysosome contact sites
Authors: Chen Xiaolong , Li Chun Guang , Zhou Xian , Zhu Minghua , Jin Jing , Wang Ping
Published: September 2024

Mitochondria and lysosomes play a very important role in maintaining cellular homeostasis, and the dysfunction of these organelles is closely related to many diseases. Recent studies have revealed direct interactions between mitochondria and lysosomes, forming mitochondria-lysosome contact sites that regulate organelle network dynamics and mediate the transport of metabolites between them. Impaired function of these contact sites is not only linked to physiological processes such as glucose and cholesterol transport but also closely related to the pathological processes of metabolic diseases. Here, we highlight the recent progress in understanding the mitochondria-lysosome contact sites, elucidate their role in regulating metabolic homeostasis, and explore the potential implications of this pathway in metabolic disorders.
Key microbial taxa play essential roles in maintaining soil muti-nutrient cycling following an extreme drought event in ecological buffer zones along the Yangtze River
Authors: Fang Jie , Liu Zihao , Deng Yongcui , Song Bin , Adams Jonathan M.
Published: September 2024

Climatic extremes, especially extreme droughts, are occurring more frequently and profoundly impacting biogeochemical processes. However, the relative importance of microbial communities on soil nutrient cycling and community maintenance under natural extreme drought events remains elusive. During a record-breaking drought in the Yangtze River Basin (YRB) in the summer of 2022, we collected ambient soils and drought-affected bare and vegetated soils in ecological buffer zones from two sites with similar soil and vegetation characteristics along the YRB, and examined the relative contribution of soil bacterial communities in supporting multi-nutrient cycling index (MNCI) involving carbon-, nitrate- and phosphorus-cycling and their associations with microbial network. Extreme drought decreased (p < 0.05) bacterial α-diversity but increased MNCI in vegetated soils at both sites, while both remained unchanged (p > 0.05) in bare soils, possibly as a result of vegetation releasing rhizodeposits under drought which selectively recruited bacterial communities. Bacterial community compositions were shifted (p < 0.05) only in vegetated soils, and they exerted more influence than α-diversity on soil MNCI. Notably, the Anaerolineae, identified as a biomarker enriched in vegetated soils, had close associations with enzyme activities and soil MNCI at both sites, suggesting their potential recruitment by vegetation to withstand drought. Furthermore, key ecological clusters (Module 1) in bacterial co-occurrence networks at both sites supported (p < 0.05) higher MNCI, despite no substantial variation in network structure due to drought. Specifically, the most important taxa within Module 1 for predicting soil MNCI revealed by random forest modeling analysis (R2 = 0.44 - 0.63, p < 0.001), such as B1-7BS, SBR1031 and Nocardioides, could be deeply involved in soil nitrogen-cycling, suggesting an essential role of specialized interactions of bacterial communities in maintaining soil multifunctionality. Overall, this study demonstrates that changes in biomarkers and functional taxa under extreme drought may better reflect the biological mechanisms involved in microbial communities impacting ecosystem function, which may aid in forecasting the ecological consequences of ongoing climate change in the ecological buffer zones along the YRB.