bluuebunny/crossref_metadata_2025 huggingface dataset:
1,2,3-Triazoles and their metal chelates with antimicrobial activity
Authors: Todorov Lozan , Kostova Irena
Published: August 2023

The emergence of drug-resistant bacterial and fungal pathogens has highlighted the urgent need of innovative antimicrobial therapeutics. Transition metal complexes with biologically active ligands (coumarins, terpyridines, triazoles, uracils, etc.) have long been investigated for antimicrobial activity. 1,2,3-Triazoles and their molecular derivatives are well known for a plethora of physiological activities, including antibacterial and antifungal. The aim of the present mini-review is to inform the reader about research conducted on potential antimicrobial 1,2,3-triazole complexes with transition metals. What the authors find surprising is how little such research and experimentation has actually been performed and reported in scientific literature. The goal is to highlight research efforts up to now and impress upon the reader the vast perspectives for novel, effective medicinal substances hidden in this yet unexplored field.
Case Report: Clinical analysis of a cluster outbreak of chlamydia psittaci pneumonia
Authors: Wu Yinxia , Xu Xuemei , Liu Yun , Jiang Xiangwei , Wu Hongjing , Yang Jie , He Limei
Published: August 2023

Objective

To explore the clinical characteristics and prognosis of clustered cases of psittacosis pneumonia.

Method

We retrospectively analyzed the clinical data of a cluster outbreak of psittacosis pneumonia. The analysis included epidemiological data, clinical symptoms, laboratory results, and prognosis. The diagnosis was made using mNGS and nested PCR technology.

Result

Of the four cases, two had direct contact with diseased poultry while the other two did not. All cases presented with more than 39.5 °C fever and chills. Additionally, significant increases in C-reactive protein, ferritin, creatine kinase, and lactate dehydrogenase were observed in all cases, while absolute lymphocyte count decreased. Case 2 also had increased calcitonin levels. Acute respiratory failure occurred during the treatment of case 1 and case 2, leading to tracheal intubation and ventilator-assisted ventilation. Unfortunately, case 2 passed away due to sepsis and multiple organ dysfunction, while the other cases had a positive prognosis.

Conclusion

mNGS facilitated the early diagnosis of psittacosis pneumonia. It is important to note that there is still a substantial risk of human-to-human transmission in psittacosis pneumonia. Absolute lymphocyte count and calcitonin levels can predict the severity and prognosis of the disease.
Clinical magnetocardiography: the unshielded bet—past, present, and future
Authors: Brisinda D. , Fenici P. , Fenici R.
Published: August 2023

Magnetocardiography (MCG), which is nowadays 60 years old, has not yet been fully accepted as a clinical tool. Nevertheless, a large body of research and several clinical trials have demonstrated its reliability in providing additional diagnostic electrophysiological information if compared with conventional non-invasive electrocardiographic methods. Since the beginning, one major objective difficulty has been the need to clean the weak cardiac magnetic signals from the much higher environmental noise, especially that of urban and hospital environments. The obvious solution to record the magnetocardiogram in highly performant magnetically shielded rooms has provided the ideal setup for decades of research demonstrating the diagnostic potential of this technology. However, only a few clinical institutions have had the resources to install and run routinely such highly expensive and technically demanding systems. Therefore, increasing attempts have been made to develop cheaper alternatives to improve the magnetic signal-to-noise ratio allowing MCG in unshielded hospital environments. In this article, the most relevant milestones in the MCG's journey are reviewed, addressing the possible reasons beyond the currently long-lasting difficulty to reach a clinical breakthrough and leveraging the authors’ personal experience since the early 1980s attempting to finally bring MCG to the patient's bedside for many years thus far. Their nearly four decades of foundational experimental and clinical research between shielded and unshielded solutions are summarized and referenced, following the original vision that MCG had to be intended as an unrivaled method for contactless assessment of the cardiac electrophysiology and as an advanced method for non-invasive electroanatomical imaging, through multimodal integration with other non-fluoroscopic imaging techniques. Whereas all the above accounts for the past, with the available innovative sensors and more affordable active shielding technologies, the present demonstrates that several novel systems have been developed and tested in multicenter clinical trials adopting both shielded and unshielded MCG built-in hospital environments. The future of MCG will mostly be dependent on the results from the ongoing progress in novel sensor technology, which is relatively soon foreseen to provide multiple alternatives for the construction of more compact, affordable, portable, and even wearable devices for unshielded MCG inside hospital environments and perhaps also for ambulatory patients.
Low-carbon economic operation of IES based on life cycle method and hydrogen energy utilization
Authors: Xie Weiqiang , Li Xiaoyun
Published: August 2023

The Integrated Energy System (IES) that coordinates multiple energy sources can effectively improve energy utilization and is of great significance to achieving energy conservation and emission reduction goals. In this context, a low-carbon and economic dispatch model for IES is proposed. Firstly, a hydrogen energy-based IES (H2-IES) is constructed to refine the utilization process of hydrogen energy. Secondly, the carbon emissions of different energy chains throughout their life cycle are analyzed using the life cycle assessment method (LCA), and the carbon emissions of the entire energy supply and demand chain are considered. Finally, a staged carbon trading mechanism is adopted to promote energy conservation and emission reduction. Based on this, an IES low-carbon and economic dispatch model is constructed with the optimization goal of minimizing the sum of carbon trading costs, energy procurement costs, and hydrogen sales revenue, while considering network constraints and constraints on key equipment. By analyzing the model under different scenarios, the introduction of life cycle assessment, staged carbon trading, and hydrogen energy utilization is shown to promote low-carbon and economic development of the comprehensive energy system.
Caribbean small island developing states must incorporate water quality and quantity in adaptive management of the water-energy-food nexus
Authors: Crisman Thomas L. , Winters Zachary S.
Published: August 2023

The 10 Small Island Developing States (SIDS) of the Caribbean in this study have unsustainable water-energy-food Nexus conditions, with stress becoming more acute via climate change, population demographics and increasing tourist demands. Water resources are limited, and wastewater treatment is inadequate or missing. Nature-based solutions (NBS), especially constructed wetlands, are effective treatment options for all SIDS and have added value for recreation, conservation and product development. On islands with abundant rainfall, NBS treated water adds little to total water resources, but can be important for small scale agriculture. Rainwater harvesting is an important alternative water source for individual households and small communities, but water reuse from tourist infrastructure has the greatest potential for SIDS to reach water sustainability, while protecting coastal waters from sewage pollution. Tourism is a two-edged sword. It swells populations and associated water demand significantly and can degrade coastal waters if wastes are not treated effectively. However, a partnership among the tourist industry, local communities and national government must be given top priority to ensure sustainability of the Water-Energy-Food (WEF) Nexus in the face of progressively increasing tourist numbers and pressures. Effective governance is needed at the island and regional level to develop sound adaptative management approaches for sustainability.
Modeling spatial variation in radiata pine slenderness (height/diameter ratio) and vulnerability to wind damage under current and future climate in New Zealand
Authors: Watt Michael S. , Moore John R.
Published: August 2023

Wind is a significant disturbance agent in forests that is likely to become more prevalent as plantation forests are increasingly grown at high stand density to maximize yields and carbon sequestration. Although research has used models to characterize plantation wind risk at discrete sites, little research has regionally scaled these predictions under both current and future climate. Stem slenderness, or height/diameter ratio, has been found to be a useful proxy for stand stability in the widely grown species, radiata pine (Pinus radiata), which constitutes 90% of the New Zealand plantation area. Stands with a slenderness that exceed 80 m m–1 are likely to be at risk when exposed to strong winds. In this study, slenderness was derived from 4,004 radiata pine permanent growth monitoring plots, that covered the spatial distribution of the species, and matched with stand density, age and key climatic and edaphic variables derived from surfaces. Using these data, the objectives of this study were to (i) develop a model to predict slenderness using machine learning and partition the impacts of key factors on slenderness, (ii) use this model to spatially predict slenderness throughout New Zealand for three contrasting silvicultural regimes, under current and future climate, and (iii) identify any regions that may be particularly vulnerable to wind risk. The final model of slenderness developed using the random forest algorithm included, in order of importance, stand density, stand age, mean annual air temperature and total annual rainfall. Predictions made on a withheld independent dataset (n = 401) were both unbiased and accurate (R2 = 0.85). Spatial predictions of slenderness under current climate showed wide regional variation with mean slenderness at age 30 years increasing from 62.1 m m–1 for low stand density clearwood regimes to 73.5 m m–1 for medium stand density structural grade regimes and 79.5 m m–1 for high stand density carbon regimes. Mean changes in slenderness were relatively low to 2040 and 2090 within the North Island. In contrast, within the South Island there were moderate increases in slenderness for the three silvicultural regimes that were markedly higher for 2090 than 2040.
Optimization of tropical rainforest ecosystem management: implications from the responses of ecosystem service values to landscape pattern changes in Hainan Tropical Rainforest National Park, China, over the past 40 years
Authors: Lin Xiaofu , Fu Hui
Published: August 2023

Exploring the comprehensive impact of landscape pattern changes on regional ecosystem service values (ESVs) over a long time series is significant for optimizing ecosystem management. This study took Hainan Tropical Rainforest National Park (HTRNP) as a case and first assessed its five vital ecosystem services (ESs): water supply (WS), water purification (WP), carbon storage (CS), soil retention (SR), and habitat quality (HQ). Based on the ESs assessment results, we further calculated their ESVs and quantified the responses of ESVs to landscape pattern changes during 1980–2020. The results revealed that: (1) Forestland is the basal landscape type of HTRNP. Landscape patterns changed significantly after 2000; the proportion of both cultivated land and grassland decreased, while the proportion of forestland, water, and construction land increased; with the areas and landscape dominance of both forestland and water increased, the agglomeration and connectivity of the overall landscape increased and its homogenization decreased. (2) WS, WP, CS, and SR services tended to weaken, and HQ service tended to strengthen. The spatial heterogeneities of WS and SR changed significantly over time. WS, HQ, SR, and CS are the main contributors to the total ESV. During 1980–2020, the four ESVs of WS, WP, SR, and CS showed a decreasing trend; HQ’s ESV tended to increase, and the total ESV tended to decrease. (3) The increase of areas and dominance in forestland and water was the main reason that HQ’s ESV tended to increase, and WP’s ESV and CS’s ESV tended to decrease. The construction land scale was relatively small, so its impacts on ESVs were limited. The responses of both WS’s ESV and SR’s ESV to landscape pattern changes were insignificant due to the impacts of topographic and climatic factors. The study results provide a reference for managing and optimizing HTRNP’s ecosystem to improve its integrated benefits of crucial ESs.
Single-cell RNA-seq analysis reveals that immune cells induce human nucleus pulposus ossification and degeneration
Authors: Guo Song , Yan Meijun , Li Xinhua , Zhang Shuya , Liu Zhong , Li Kewei , Liu Pengcheng , Liu Yanbin , Sun Guixin , Fu Qiang
Published: August 2023

Background and aims

Determining the transcriptomes and molecular mechanism underlying human degenerative nucleus pulposus (NP) is of critical importance for treating intervertebral disc degeneration (IDD). Here, we aimed to elucidate the detailed molecular mechanism of NP ossification and IDD using single-cell RNA sequencing.

Methods

Single-cell RNA-seq and bioinformatic analysis were performed to identify NP cell populations with gene signatures, biological processes and pathways, and subpopulation analysis, RNA velocity analysis, and cell-to-cell communication analysis were performed in four IDD patients. We also verified the effects of immune cells on NP ossification using cultured NP cells and a well-established rat IDD model.

Results

We identified five cell populations with gene expression profiles in degenerative NP at single-cell resolution. GO database analysis showed that degenerative NP-associated genes were mainly enriched in extracellular matrix organization, immune response, and ossification. Gene set enrichment analysis showed that rheumatoid arthritis signaling, antigen processing and presentation signaling were activated in the blood cell cluster. We revealed that stromal cells, which are progenitor cells, differentiated toward an ossification phenotype and delineated interactions between immune cells (macrophages and T cells) and stromal cells. Immune factors such as TNF-α, CD74 and CCL-3 promoted the differentiation of stromal cells toward an ossification phenotype in vitro. Blocking TNF-α with a specific inhibitor successfully reversed NP ossification and modified NP morphology in vivo.

Conclusion

Our study revealed an increase in macrophages and T cells in degenerative NP, which induced stromal cell differentiation toward an ossification phenotype, and contributed to the identification of a novel therapeutic target to delay IDD.
Dupilumab improve acquired reactive perforating collagenosis characterized by type 2 inflammation
Authors: Liu Ben , Wu Yibei , Wu Xiaoyan , Zhong Xinyu , Xue Ruzeng , Zhang Zhenying
Published: August 2023

Background

Acquired reactive perforating collagenosis (ARPC) is a clinically challenging disease with an unclear pathogenesis.

Objective

To evaluate the efficacy and safety of dupilumab for the treatment of ARPC, and analyze the expression of type 2 inflammation-related molecules in ARPC lesions.

Methods

This retrospective cohort study included 20 patients with ARPC; 10 received dupilumab and 10 received conventional therapy. The efficacy and safety of dupilumab were evaluated at 12 weeks. Immunohistochemical and immunofluorescence analyses of T- and B-cell markers, and type 2 inflammation-related cytokines, were performed on skin samples from ARPC patients, atopic dermatitis (AD) patients, and healthy controls.

Results

Significantly more patients showed improvements in the Investigator Global Assessment score (100% vs. 0%; p < 0.0001) and itching (90%/8.33%, P =.001) in the dupilumab group compared to the conventional group at 12 weeks. There were no adverse effects in the dupilumab group. The ARPC lesions showed enhanced dermal infiltration of CD3+ T-cells, with a predominance of Th2 cells, similar to AD lesions. IL-4 and IL-13 were co-localized with GATA3 in ARPC lesions.

Conclusion

Dupilumab improved ARPC charaterized with type 2 inflammation.
Remote sensing-based spatiotemporal variation and driving factor assessment of chlorophyll-a concentrations in China’s Pearl River Estuary
Authors: Fan Wenjie , Xu Zhihao , Dong Qian , Chen Weiru , Cai Yanpeng
Published: August 2023

Climate change and intensive anthropogenic activities have severely challenged the water quality of China’s Pearl River Estuary (PRE). Further investigations into long-term water quality variation and associated driving mechanisms are therefore necessary to support the sustainable development of the PRE’s Greater Bay Area (GBA). This study used remote sensing retrieval to address long-term spatiotemporal chlorophyll-a (Chl-a) variation characteristics in the PRE and the relationship between Chl-a concentrations and socioeconomic/environmental indicators. Three decades of Landsat satellite images and measured data were collected, and a two-band global algorithm was used to retrieve Chl-a concentration data. Results reveal significant spatiotemporal variability in Chl-a concentrations. The space-averaged Chl-a concentration exhibited a slight downward trend during the past three decades, and the multi-year mean value was 5.20 mg/L. Changes to environmental protection policies in recent years have improved overall PRE water quality. The western section of the PRE had the highest Chl-a concentration (i.e., 5.92 mg/L average) while the eastern section had the lowest (i.e., 3.98 mg/L average). This discrepancy was likely caused by the western section’s more intensive industrial activities, resulting in a higher overall wastewater discharge volume. Affected by climatic conditions, winter Chl-a concentrations were evenly distributed while summer concentrations were significantly higher. Additionally, Chl-a concentrations significantly and positively correlated with total phosphorus (TP), total nitrogen (TN), ammonia nitrogen (NH3-N), and the biotic oxygen demand (BOD5). Chl-a concentrations also correlated with external factors (i.e., climate and anthropogenic activities). Among these factors, industrial wastewater discharge and the proportion of primary industries in coastal cities significantly and positively correlated with water quality. This study is intended to help direct water quality improvement management and urban sustainable development in the GBA.
Estimation of subsurface salinity and analysis of Changjiang diluted water volume in the East China Sea
Authors: Kim So-Hyun , Shin Jisun , Kim Dae-Won , Jo Young-Heon
Published: August 2023

In the East China Sea (ECS), the sea surface salinity (SSS) changes as the Changjiang Diluted Water (CDW) propagates toward the Korean Peninsula via the ocean current and winds every summer annually. Although the vertical stratifications resulting from the CDW volume changes are important, it has not been analyzed yet. Therefore, in this study, we aimed to estimate the salinity at a depth of 10 m (S10m) using convolutional neural network (CNN) model based on multi-satellite measurements and analyze CDW volume variations. The main CDW mass in the ECS reaches approximately 10 m in depth; thus, the CNN model was developed using sea surface physical factors as input and in situ S10m obtained from the National Institute of Fisheries Science (NIFS) as ground truth data from 2015 to 2021. The CNN tests result showed a determination coefficient (R2) of 0.81, root mean square error (RMSE) of 0.63 psu, and relative RMSE (RRMSE) of 2.00%. Unlike the sea surface distribution, the spatial distribution of S10m showed that the CDW was predominantly present in the center of the ECS. From SHapley Additive exPlanations (SHAP) analysis, SSS exhibited a strong positive relationship with S10m, and the sea level anomaly showed a strong negative relationship. After calculating the volume of the CDW from the surface to a depth of 10 m, the maximum (3.01×1012 m3) and minimum volumes (1.31×1012 m3) were represented in 2016 and 2018, respectively. Finally, the warming effect induced by the CDW volume changes was analyzed in two different years: 2016 and 2018. Specifically, in 2016, the sea surface temperature increased by more than 4.79 °C in the Ieodo location, while in 2018, it increased by 2.19 °C. Thus, our findings can obtain information about the volume variation of the CDW and its effect on the ECS in summer.
Prevalence and risk factors of malnutrition in patients with pulmonary tuberculosis: a systematic review and meta-analysis
Authors: Li Ai , Yuan Su-yun , Li Quan-guo , Li Jin-xing , Yin Xiang-yu , Liu Na-na
Published: August 2023

Background

Malnutrition is prevalent in patients with pulmonary tuberculosis (PTB) and is associated with a poor prognosis.

Objective

This study aims to assess the prevalence and risk factors of malnutrition in patients with PTB.

Methods

Studies related to the prevalence and risk factors of malnutrition in patients with PTB were searched through PubMed, Embase, Web of Science, and Cochrane Library databases from January 1990 to August 2022, and two researchers screened the literature, evaluated the quality, and extracted data independently. A random-effects model was used to pool the effect sizes and 95% confidence intervals. Subgroup analysis, meta-regression analysis, and sensitivity analysis were further performed to identify sources of heterogeneity and evaluate the stability of the results. Publication bias was assessed by Doi plot, Luis Furuya-Kanamori (LFK) asymmetry index, funnel plot, and Egger's tests.

Results

A total of 53 studies involving 48, 598 participants were identified in this study. The prevalence of malnutrition was 48.0% (95% CI, 40.9–55.2%). Subgroup analysis revealed that malnutrition was more common among male gender (52.3%), bacterial positivity (55.9%), family size over 4 (54.5%), drug resistance (44.1%), residing in rural areas (51.2%), HIV infection (51.5%), Asian (51.5%), and African (54.5%) background. The prevalence of mild, moderate, and severe malnutrition was 21.4%, 14.0%, and 29.4%, respectively. Bacterial positivity (OR = 2.08, 95% CI 1.26–3.41), low income (OR = 1.44, 95% CI 1.11–1.86), and residing in rural areas (OR = 1.51, 95% CI 1.20–1.89) were risk factors of malnutrition in patients with PTB. However, male (OR = 1.04, 95% CI 0.85–1.26) and drinking (OR = 1.17, 95% CI 0.81–1.69) were not risk factors for malnutrition in patients with PTB. Due to the instability of sensitivity analysis, HIV infection, age, family size, smoking, and pulmonary cavity need to be reevaluated. Meta-regression suggested that sample size was a source of heterogeneity of prevalence. The Doi plot and LFK asymmetry index (LFK = 3.87) indicated the presence of publication bias for prevalence, and the funnel plot and Egger's test showed no publication bias for risk factors.

Conclusion

This meta-analysis indicated that malnutrition was prevalent in patients with PTB, and bacterial positivity, low income, and those residing in rural areas were risk factors for malnutrition. Therefore, clinical workers should pay attention to screening the nutritional status of patients with PTB and identifying the risk factors to reduce the incidence of malnutrition and provide nutritional interventions early to improve the prognosis in patients with PTB.
Neutrophil extracellular traps−related signature predicts the prognosis and immune infiltration in gastric cancer
Authors: Li Mingzhe , Zhao Zidan , Mak Tsz Kin , Wang Xiaoqun , Chen Jingyao , Ren Hui , Yu Zhiwei , Zhang Changhua
Published: August 2023

Introduction

Gastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown.

Methods

The keywords “neutrophil extracellular traps and gastric cancer” were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis (p < 0.05). 27 NETs-related genes were employed to identify and categorize NETs-subgroups of GC patients under the Consensus clustering analysis. 808 GC patients in TCGA-STAD combined with GES84437 were randomly divided into a training group (n = 403) and a test group (n = 403) at a ratio of 1:1 to validate the NETs-related signature.

Results

Based on Multivariate Cox regression and LASSO regression analysis to develop a NETs-related prognosis model. We developed a very specific nomogram to improve the NETs-clinical score’s usefulness. Similarly, we also performed a great result in pan-cancer study with NETs-score. Low NETs scores were linked to higher MSI-H (microsatellite instability-high), mutation load, and immune activity. The cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity were also connected to the NET score. Our comprehensive analysis of NETs in GC suggests that NETs have a role in the tumor microenvironment, clinicopathological features, and prognosis.

Discussion

The NETs-score risk model provides a basis for better prognosis and therapy outcomes in GC patients.
Geometric morphometrics and machine learning from three-dimensional facial scans for difficult mask ventilation prediction
Authors: Pei Bei , Jin Chenyu , Cao Shuang , Ji Ningning , Xia Ming , Jiang Hong
Published: August 2023

Background

Unanticipated difficult mask ventilation (DMV) is a potentially life-threatening event in anesthesia. Nevertheless, predicting DMV currently remains a challenge. This study aimed to verify whether three dimensional (3D) facial scans could predict DMV in patients scheduled for general anesthesia.

Methods

The 3D facial scans were taken on 669 adult patients scheduled for elective surgery under general anesthesia. Clinical variables currently used as predictors of DMV were also collected. The DMV was defined as the inability to provide adequate and stable ventilation. Spatially dense landmarks were digitized on 3D scans to describe sufficient details for facial features and then processed by 3D geometric morphometrics. Ten different machine learning (ML) algorithms, varying from simple to more advanced, were introduced. The performance of ML models for DMV prediction was compared with that of the DIFFMASK score. The area under the receiver operating characteristic curves (AUC) with its 95% confidence interval (95% CI) as well as the specificity and sensitivity were used to evaluate the predictive value of the model.

Results

The incidence of DMV was 35/669 (5.23%). The logistic regression (LR) model performed best among the 10 ML models. The AUC of the LR model was 0.825 (95% CI, 0.765–0.885). The sensitivity and specificity of the model were 0.829 (95% CI, 0.629–0.914) and 0.733 (95% CI, 0.532–0.819), respectively. The LR model demonstrated better predictive performance than the DIFFMASK score, which obtained an AUC of 0.785 (95% CI, 0.710–0.860) and a sensitivity of 0.686 (95% CI, 0.578–0.847). Notably, we identified a significant morphological difference in the mandibular region between the DMV group and the easy mask ventilation group.

Conclusion

Our study indicated a distinct morphological difference in the mandibular region between the DMV group and the easy mask ventilation group. 3D geometric morphometrics with ML could be a rapid, efficient, and non-invasive tool for DMV prediction to improve anesthesia safety.
Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients
Authors: Mori Tatsuhiko , Namikawa Kenjiro , Yamazaki Naoya , Kiniwa Yukiko , Yamasaki Osamu , Yoshikawa Shusuke , Inozume Takashi , Kato Hiroshi , Nakai Yasuo , Fukushima Satoshi , Takenouchi Tatsuya , Maekawa Takeo , Matsushita Shigeto , Otsuka Atsushi , Nomura Motoo , Baba Natsuki , Isei Taiki , Saito Shintaro , Fujimoto Noriki , Tanaka Ryo , Kaneko Takahide , Kuwatsuka Yutaka , Matsuya Taisuke , Nagase Kotaro , Onishi Masazumi , Onuma Takehiro , Nakamura Yasuhiro
Published: August 2023

Background

Anti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF.

Patients and methods

The study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

Thirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p < 0.001). Cox multivariate analysis demonstrated that nail apparatus melanoma independently predicted unfavorable PFS and OS (p = 0.006 and 0.001). The total OS (from PD-1 monotherapy initiation to death/last follow-up) was insignificant between the groups.

Conclusion

Nivo/ipi was not more effective than cytotoxic chemotherapy and ipilimumab after PD-1 MF in patients with advanced AM. The prognosis after PD-1 MF would be poorer for nail apparatus melanoma than for palm and sole melanoma.
A sweet new set of inducible and constitutive promoters in Haloferax volcanii
Authors: Rados Theopi , Andre Katherine , Cerletti Micaela , Bisson Alex
Published: August 2023

Inducible promoters are one of cellular and molecular biology’s most important technical tools. The ability to deplete, replete, and overexpress genes on demand is the foundation of most functional studies. Here, we developed and characterized a new xylose-responsive promoter (Pxyl), the second inducible promoter system for the model haloarcheon Haloferax volcanii. Generating RNA-seq datasets from cultures in the presence of four historically used inducers (arabinose, xylose, maltose, and IPTG), we mapped upregulated genomic regions primarily repressed in the absence of the above inducers. We found a highly upregulated promoter that controls the expression of the xacEA (HVO_B0027-28) operon in the pHV3 chromosome. To characterize this promoter region, we cloned msfGFP (monomeric superfold green fluorescent protein) under the control of two upstream regions into a modified pTA962 vector: the first 250 bp (P250) and the whole 750 bp intergenic fragments (P750). The P250 sequence drove the expression of msfGFP constitutively, and its expression did not respond to the presence or absence of xylose. However, the P750 promoter showed not only to be repressed in the absence of xylose but also expressed higher levels of msfGFP than the previously described inducible promoter PtnaA in the presence of the inducer. Finally, we validated the inducible Pxyl promoter by reproducing morphological phenotypes already described in the literature. By overexpressing the tubulin-like FtsZ1 and FtsZ2, we observed similar but slightly more pronounced morphological defects than the tryptophan-inducible promoter PtnaA. FtsZ1 overexpression created larger, deformed cells, whereas cells overexpressing FtsZ2 were smaller but mostly retained their shape. In summary, this work contributes a new xylose-inducible promoter that could be used simultaneously with the well-established PtnaA in functional studies in H. volcanii in the future.
Effects of moderate drought extension on bacterial network structure in the rhizosphere soil of Leymus chinensis in semi-arid grasslands
Authors: Wang Jinlong , Wang Chunjuan , Wu Xuefeng , Zhang Jinwei , Zhao Guiyun , Hou Yu , Sun Haiming
Published: August 2023

Introduction

Grasslands are home to complex bacterial communities whose dynamic interactions play a crucial role in organic matter and nutrient cycling. However, there is limited understanding regarding the impact of changes in rainfall amount and the duration of dry intervals on bacterial interactions.

Methods

To assess the impact of changes in precipitation volume and dry intervals on bacterial co-occurrence networks, we carried out precipitation manipulation experiments in the Eastern Eurasian Steppe of China.

Results and Discussion

We found that alterations in precipitation and dry intervals did not significantly affect bacterial alpha and beta diversity. However, we observed significant changes in the co-occurrence network structure of bacteria in the rhizosphere ecosystem, with the 12-day dry interval showing the most notable reduction in the number of degrees, edges, and clustering coefficient. Additionally, the study identified putative keystone taxa and observed that the moderately prolonged dry intervals between precipitation events had a major effect on the robustness of bacterial networks. The complexity and stability of the network were found to be positively correlated, and were primarily influenced by soil water content, phosphorous, and aboveground biomass, followed by available phosphorus (AP) and total biomass. These findings have the potential to enhance our comprehension of how bacterial co-occurrence pattern react to variations in dry intervals, by regulating their interactions in water-limited ecosystems. This, in turn, could aid in predicting the impact of precipitation regime alterations on ecosystem nutrient cycling, as well as the feedback between ecosystem processes and global climate change.
Effects of tea oil camellia (Camellia oleifera Abel.) shell-based organic fertilizers on the physicochemical property and microbial community structure of the rhizosphere soil
Authors: Huang Anxiang , Wang Zhongwei , Yang Dingyun , Yang Shoulu , Bai Wennian , Wu Nengying , Lu Xiang , Liu Zhu
Published: August 2023

Soil microorganisms play important roles in promoting soil ecosystem restoration, but much of the current research has been limited to changes in microbial community structure in general, and little is known regarding the soil physicochemical property and microbial community structure. In this study, four organic fertilizers were first prepared based on tea oil camellia shell (TOCS). Our findings indicate that the application of BOFvo increased both total pore volume and BET surface area of the rhizosphere soils, as well there was a remarkable enhancement in total organic matter (TOM), total nitrogen (TN), available nitrogen (AN), total phosphorus (TP), total potassium (TK), and available potassium (AK) contents of the rhizosphere soils. Meanwhile, in comparison to the CK and CF groups, the utilization of BOFvo led to a substantial increase in both average yield and fruiting rate per plant at maturity, as well resulted in a significant increase in TN and TP contents of tea oil camellia leaves. Furthermore, our findings suggest that the application of TOCS-based organic fertilizers significantly enhances the microbial diversity in the rhizosphere soils with Proteobacteria and Ascomycota being the dominant bacterial and fungal phyla, respectively, and Rhodanobacter and Fusarium being the dominant bacterial and fungal genus, respectively. Redundancy analysis (RDA) indicates that the physicochemical characteristics of TOCS-based organic fertilizers had a significant impact on the composition and distribution of microbial communities in the rhizosphere soils. This study will facilitate the promotion and application of TOCS-based organic fertilizers, thereby establishing a foundation for the reuse of tea oil camellia waste resources.
Development of a methodology for large-scale production of prions for biological and structural studies
Authors: Concha-Marambio Luis , Wang Fei , Armijo Enrique , Gorski Damian , Ramirez Frank , Scowcroft Andrew , Pritzkow Sandra , Soto Claudio
Published: August 2023

Prion diseases are a group of infectious neurodegenerative diseases produced by the conversion of the normal prion protein (PrPC) into the disease-associated form (PrPSc). Extensive evidence indicate that the main or sole component of the infectious agent is PrPSc, which can replicate in affected individuals in the absence of nucleic acids. However, the mechanism of PrPC-to-PrPSc conversion remains elusive, which has been attributed to the lack of sufficient structural information of infectious PrPSc and a reliable system to study prion replication in vitro. In this article we adapted the Protein Misfolding Cyclic Amplification (PMCA) technology for rapid and efficient generation of highly infectious prions in large-scale. Murine prions of the RML strain were efficiently propagated in volumes up to 1,000-fold larger than conventional PMCA. The large-scale PMCA (LS-PMCA) procedure enabled to produce highly infectious prions, which maintain the strain properties of the seed used to begin the reaction. LS-PMCA was shown to work with various species and strains of prions, including mouse RML and 301C strains, hamster Hyper prion, cervid CWD prions, including a rare Norwegian CWD prion, and human CJD prions. We further improved the LS-PMCA into a bioreactor format that can operate under industry-mimicking conditions for continuous and unlimited production of PrPSc without the need to keep adding brain-derived prions. In our estimation, this bioreactor can produce in 1d an amount of prions equivalent to that present in 25 infected animals at the terminal stage of the disease. Our LS-PMCA technology may provide a valuable tool to produce large quantities of well-defined and homogeneous infectious prions for biological and structural studies.
Probing magnetization dynamics of iron oxide nanoparticles using a point-probe magneto-optical method
Authors: Wang Xuyiling , Cabrera David , Yang Ying , Telling Neil
Published: August 2023

Magnetic nanoparticles (MNPs) are promising as local heat generators for magnetic hyperthermia under AC magnetic fields. The heating efficacy of MNPs is determined by the AC hysteresis loop area, which in turn is affected by the dynamic magnetic properties of the nanoparticles. Whilst inductive-based AC magnetometers can measure the average magnetic behavior of samples, the use of the magneto-optical Faraday effect with a focused laser spot allows point-probe measurements to be made, and without some of the magnetic field limitations imposed by inductive methods. In this work, the AC magnetic properties of different sized iron oxide MNPs in suspension were measured by AC magnetometry and AC susceptibility techniques. AC hysteresis loops measured by magneto-optical magnetometry were validated using a commercial inductive AC magnetometer, and compared to the magnetization relaxation behavior revealed by fitting the AC susceptibility data. The spatial sensitivity of the point-probe magneto-optical method is also demonstrated by measuring the AC hysteresis loop from large (>1 μm) MNP aggregates dried onto glass slides. These aggregated particles are found to be magnetically softer than in their suspension form, suggesting interparticle coupling mechanisms could occur when the nanoparticles form dense aggregates.
Cofilin overactivation improves hippocampus-dependent short-term memory
Authors: Raven Frank , Riemersma Iris W. , Olthuis Martha F. , Rybakovaite Ieva , Meijer Elroy L. , Meerlo Peter , Van der Zee Eddy A. , Havekes Robbert
Published: August 2023

Many living organisms of the animal kingdom have the fundamental ability to form and retrieve memories. Most information is initially stored as short-term memory, which is then converted to a more stable long-term memory through a process called memory consolidation. At the neuronal level, synaptic plasticity is crucial for memory storage. It includes the formation of new spines, as well as the modification of existing spines, thereby tuning and shaping synaptic efficacy. Cofilin critically contributes to memory processes as upon activation, it regulates the shape of dendritic spines by targeting actin filaments. We previously found that prolonged activation of cofilin in hippocampal neurons attenuated the formation of long-term object-location memories. Because the modification of spine shape and structure is also essential for short-term memory formation, we determined whether overactivation of hippocampal cofilin also influences the formation of short-term memories. To this end, mice were either injected with an adeno-associated virus expressing catalytically active cofilin, or an eGFP control, in the hippocampus. We show for the first time that cofilin overactivation improves short-term memory formation in the object-location memory task, without affecting anxiety-like behavior. Surprisingly, we found no effect of cofilin overactivation on AMPA receptor expression levels. Altogether, while cofilin overactivation might negatively impact the formation of long-lasting memories, it may benefit short-term plasticity.
Ipsilateral and contralateral carotid stenosis contribute to the outcome of reperfusion treatment for ischemic stroke
Authors: Viticchi Giovanna , Falsetti Lorenzo , Riva Alice , Paolucci Silvia , Malatini Simone , Guerrieri Emanuele , Bartolini Marco , Silvestrini Mauro
Published: August 2023

Introduction

Ipsilateral and contralateral carotid stenosis (ICS, CCS) influence acute ischemic stroke (AIS) severity and prognosis. Few data are available about their impact on reperfusion therapies efficacy. Aim of this study was to evaluate the impact of ICS and CCS on the effect of intravenous thrombolysis (IT), mechanical thrombectomy (MT) or both and of antiplatelet therapy (AT).

Methods

We enrolled all the consecutive patients admitted for AIS to our stroke unit and submitted to IT, MT, IT+MT, or AT. We established the presence of a significant ICS or CCS (≥70%) by ultrasound examination or brain angio-CT, or MRI. Clinical and instrumental information were collected; delta National Institutes of Health Stroke Scale (NIHSS) from pre-treatment to patients' discharge was employed as the main outcome measure.

Results

In total, 460 subjects were enrolled, 86 with ICS and 38 with CCS. We observed a significant linear trend of delta (NIHSS) between carotid stenosis categories for patients undergoing IT (p = 0.011), MT (p = 0.046), and MT+IT (p = 0.040), but no significant trend among subjects receiving no reperfusion treatments was observed (p = 0.174).

Discussion

According to our findings, ICS and CCS negatively influence AIS patients' outcome treated by interventional therapies. ICS might exert an unfavorable effect both by cerebral hypoperfusion and by continuous microembolization toward ischemic area, while CCS is probable involved in reducing the collateral circles effectiveness. The importance of early carotid stenosis detection and treatment should then be reevaluated not only to manage the prevention approaches but also to obtain insights about post-stroke treatment strategies efficacy.
Exploring the feasibility of tensor decomposition for analysis of fNIRS signals: a comparative study with grand averaging method
Authors: Chan Jasmine Y. , Hssayeni Murtadha D. , Wilcox Teresa , Ghoraani Behnaz
Published: August 2023

The analysis of functional near-infrared spectroscopy (fNIRS) signals has not kept pace with the increased use of fNIRS in the behavioral and brain sciences. The popular grand averaging method collapses the oxygenated hemoglobin data within a predefined time of interest window and across multiple channels within a region of interest, potentially leading to a loss of important temporal and spatial information. On the other hand, the tensor decomposition method can reveal patterns in the data without making prior assumptions of the hemodynamic response and without losing temporal and spatial information. The aim of the current study was to examine whether the tensor decomposition method could identify significant effects and novel patterns compared to the commonly used grand averaging method for fNIRS signal analysis. We used two infant fNIRS datasets and applied tensor decomposition (i.e., canonical polyadic and Tucker decompositions) to analyze the significant differences in the hemodynamic response patterns across conditions. The codes are publicly available on GitHub. Bayesian analyses were performed to understand interaction effects. The results from the tensor decomposition method replicated the findings from the grand averaging method and uncovered additional patterns not detected by the grand averaging method. Our findings demonstrate that tensor decomposition is a feasible alternative method for analyzing fNIRS signals, offering a more comprehensive understanding of the data and its underlying patterns.
A multidimensional investigation of the relationship between skin-mediated somatosensory signals, emotion regulation and behavior problems in autistic children
Authors: Riquelme Inmaculada , Hatem Samar M. , Sabater-Gárriz Álvaro , Montoya Pedro
Published: August 2023

Introduction

Autistic children may have abnormal sensory perception, emotion dysregulation and behavior problems. The aim of this cross-sectional study was to explore the relationship between skin-mediated somatosensory signals and emotion/behavior difficulties in autistic children and adolescents, in comparison typically developing peers (TDP).

Methods

Thirty-eight autistic children and adolescents and 34 TDP completed a multidimensional assessment consisting of the measurement of somatosensory thresholds of touch, pain and temperature, a task on emotion knowledge and parent-reported questionnaires on sensory reactivity, emotion regulation and behavior.

Results

Autistic children had higher pain sensitivity, less sensory reactive behaviors and more behavior problems than their TDP. In contrast to TDP, several somatosensory thresholds of autistic children correlated with emotion regulation and behavior problems.

Discussion

Sensory dysfunction may affect the development of emotional processing and behavior in autistic children and adolescents. This knowledge can lay the foundation for future studies on co-occurring alterations in corresponding neural networks and for the implementation of early interventions, including sensory rehabilitation therapy, for promoting regulated behaviors in autistic children and adolescents.
Daprodustat: A potential game-changer in renal anemia therapy—A perspective
Authors: Haider Muhammad Usman , Furqan Muhammad , Mehmood Qasim
Published: August 2023

The United States FDA has approved daprodustat (DPD) as the first oral treatment option for anemia due to chronic kidney disease (CKD) in dialysis patients. Clinical trials have demonstrated DPD’s efficacy and safety, showing non-inferiority to darbepoetin and suggesting reduced IV iron usage. DPD also holds potential for treating chronic kidney disease anemia in non-dialysis patients and may have benefits for patients with coexisting renal anemia and heart failure, pending further research and trials.