bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non-coding RNAs and JAK/STAT signaling pathway regulation in colorectal cancer development
Authors: Ghasemian Abdolmajid , Omear Hadeel A. , Mansoori Yaser , Mansouri Pardis , Deng Xinpei , Darbeheshti Farzaneh , Zarenezhad Elham , Kohansal Maryam , Pezeshki Babak , Wang Zhangling , Tang Hailin
Published: November 2023

Colorectal cancer (CRC) is one of the main fatal cancers. Cell signaling such as Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling substantially influences the process of gene expression and cell growth. Long non-coding RNAs (lncRNAs) play regulatory roles in cell signaling, cell proliferation, and cancer fate. Hence, lncRNAs can be considered biomarkers in cancers. The inhibitory or activating effects of different lncRNAs on the JAK/STAT pathway regulate cancer cell proliferation or tumor suppression. Additionally, lncRNAs regulate immune responses which play a role in immunotherapy. Mechanisms of lncRNAs in CRC via JAK/STAT regulation mainly include cell proliferation, invasion, metastasis, apoptosis, adhesion, and control of inflammation. More profound findings are warranted to specifically target the lncRNAs in terms of activation or suppression in hindering CRC cell proliferation. Here, to understand the lncRNA cross-talk in CRC through the JAK/STAT signaling pathway, we collected the related in vitro and in vivo data. Future insights may pave the way for the development of novel diagnostic tools, therapeutic interventions, and personalized treatment strategies for CRC patients.
Early autoantibody screening for type 1 diabetes: a Kuwaiti perspective on the advantages of multiplexing chemiluminescent assays
Authors: Al-Mulla Fahd , Alhomaidah Doha , Abu-Farha Mohamed , Hasan Amal , Al-Khairi Irina , Nizam Rasheeba , Alqabandi Rawan , Alkandari Hessa , Abubaker Jehad
Published: November 2023

Type 1 diabetes (T1D) incidence has increased globally over the last decades, alongside other autoimmune diseases. Early screening of individuals at risk of developing T1D is vital to facilitate appropriate interventions and improve patient outcomes. This is particularly important to avoid life-threatening diabetic ketoacidosis and hospitalization associated with T1D diagnosis. Additionally, considering that new therapies have been developed for T1D, screening the population and individuals at high risk would be of great benefit. However, adopting such screening approaches may not be feasible due to limitations, such as cost, adaptation of such programs, and sample processing. In this perspective, we explore and highlight the use of multiplexing chemiluminescent assays for T1D screening and emphasize on their advantages in detecting multiple autoantibodies simultaneously, maximizing efficiency, and minimizing sample volume requirements. These assays could be extremely valuable for pediatric populations and large-scale screening initiatives, providing a cost-efficient solution with increased diagnostic accuracy and deeper insights into T1D pathogenesis. Eventually, the adoption of such screening methods can help transform T1D diagnosis, especially in countries with high T1D prevalence, such as Kuwait, which will contribute to the development of novel therapeutic interventions, positively impacting the lives of those affected by T1D and other autoimmune diseases.
Bioavailable central nervous system disease-modifying therapies for multiple sclerosis
Authors: Hartung Hans-Peter , Cree Bruce A.C. , Barnett Michael , Meuth Sven G. , Bar-Or Amit , Steinman Lawrence
Published: November 2023

Disease-modifying therapies for relapsing multiple sclerosis reduce relapse rates by suppressing peripheral immune cells but have limited efficacy in progressive forms of the disease where cells in the central nervous system play a critical role. To our knowledge, alemtuzumab, fumarates (dimethyl, diroximel, and monomethyl), glatiramer acetates, interferons, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and teriflunomide are either limited to the periphery or insufficiently studied to confirm direct central nervous system effects in participants with multiple sclerosis. In contrast, cladribine and sphingosine 1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are central nervous system-penetrant and could have beneficial direct central nervous system properties.
Satellite to buoy IoT communications in the Arctic Ocean
Authors: Røste Terje , Yang Kun , Wen Chengyuan
Published: November 2023

Internet of things (IoT), to Arctic Ocean areas using Low Earth Orbit (LEO) satellites for communication to and from sensor units on the sea, has become increasingly important. It is challenging to close the link budget from a buoy on sea to a LEO satellite due to restrictions on the availability of power in such installations. Phenomena as scattering from the sea surface and small-scale fading, ionospheric scintillations, diffraction loss at low elevation angles, and power availability in small LEO satellites and models for analysis are described. It is of great importance to have a radio wave propagation model that accurately predicts path loss between an installation on the sea and a LEO satellite taking all loss mechanisms into account. In this paper, a path-loss model for satellite to buoy communications over the sea is described. In this model, maritime propagation phenomena in the radio link include free space loss, scintillation loss caused by the ionosphere, diffraction loss at low elevation angle, and scattering at the sea surface depending on the wave height and small-scale fading. Furthermore, a buoy on the sea surface with strong angular movement will cause a varying receive signal level depending on the antenna diagram. These phenomena are assessed. A link budget for the frequencies 433, 868, and 3,400 MHz is calculated for a LEO satellite at a height of 800 km.
Synthesis of organic photothermal agents for combined photothermal/enzymatic dynamic therapy of breast cancer
Authors: Zhang Meifeng , Huang Qian , Zhang Bo , Wu Wei
Published: November 2023

Nanoparticle-based photothermal therapy is an effective treatment for superficial tumors. However, due to the highly heterogeneous nature of breast cancer, photothermal therapy (PTT) used alone was unable to achieve satisfactory therapeutic results. Therefore, combining PTT with other therapies is a promising strategy for tumor treatment. Inspired by the significant elevation of lactate levels at the tumor site, we prepared a novel nanocomposite therapeutic platform (PPy-LOX) for combined PTT and enzyme dynamic treatment (EDT) of breast cancer. In detail, Polypyrrole (PPy) nanoparticles were synthesized using a simple chemical oxygenation method and polyvinylpyrrolidone (PVP) was used as a surface linker to enhance its colloidal stability. Further, the loading of lactate oxidase (LOX) is accomplished by simple physical mixing. The in vivo and in vitro results demonstrated the excellent biocompatibility of the synthesized PPy-LOX NPs. More importantly, PPy-LOX NPs has excellent photothermal conversion (η = 29.9%) and lactic acid catalytic ability. On the one hand, the temperature increase induced by near-infrared light irradiation can cause apoptosis of tumor cells; on the other hand, LOX can catalyze the generation of hydrogen peroxide from excess lactate in the tumor microenvironment to induce oxidative stress to kill tumor cells. In conclusion, the combination of PTT and EDT can effectively kill tumor cells. This work provides new ideas on how to design rational nanotherapeutic systems by exploiting the tumor microenvironment.
A systematic review of pregnancy-related clinical intervention of drug regimens due to pharmacokinetic reasons
Authors: Borda Lauren A. , Någård Mats , Boulton David W. , Venkataramanan Raman , Coppola Paola
Published: November 2023

Background and objective

Published works have discussed the pharmacokinetic interactions of drugs with pregnancy, but none comprehensively identify all the approved United States Food and Drug Administration (FDA) and European Medicines Administration (EMA) drugs that have a pregnancy-related intervention. The objective of this systematic review is to comprehensively identify medications that have clinically meaningful interventions due to pharmacokinetic reasons.

Methods

An in-depth search of clinical data using the PDR3D: Reed Tech Navigator™ for Drug Labels was conducted from 1 June to 12 August 2022. The PDR3D was analyzed using the search terms “pregnant” and “pregnancy” within the proper label section. Regarding the US labels, the terms were searched under the “dosage and administration” section, whereas with the EU labels, the terms were searched within the “posology and method of administration” section. If a finding was discovered within the search, the rest of the label was analyzed for further information. Clinical relevance was based on whether an intervention was needed.

Results

Using the search strategy, 139 US and 20 EU medications were found to have clinically meaningful interventions in pregnancy. The most common explanations for clinical relevance included hepatic metabolism, protein binding, renal elimination, and P-gp influence. Of the US labels: 40 were found to undergo hepatic metabolism, 11 were found to be influenced by renal elimination, 12 were found to be influenced by protein binding, 7 were found to be influenced by P-gp, and the remaining drugs required further research. Of the EU labels: 11 were found to undergo hepatic metabolism, 3 were found to be influenced by renal elimination, 3 were found to be influenced by protein binding, 1 was found to be influenced by P-gp, and the remaining drugs required further research.

Conclusion

This comprehensive review of clinically relevant interventions in pregnancy will potentially aid in the treatment of pregnant females when they are undergoing therapy, provide intervention and dosing guidance for physicians, and save time for prescribers and pharmacists. Advances in non-clinical predictions for pregnancy dosing may guide the need for a future clinical evaluation.
Exploring the risk factors of early sepsis after liver transplantation: development of a novel predictive model
Authors: Chen Wanting , Wu Shengdong , Gong Lingwen , Guo Yu , Wei Li , Jin Haoran , Zhou Yan , Li Chuanshuang , Lu Caide , Xu Lanman
Published: November 2023

Background

Sepsis is a severe and common complication of liver transplantation (LT) with a high risk of mortality. However, effective tools for evaluating its risk factors are lacking. Therefore, this study identified the risk factors of early post-liver transplantation sepsis and established a nomogram.

Methods

We analyzed the risk factors of post-liver transplantation sepsis in 195 patients. Patients with infection and a systemic inflammatory response syndrome (SIRS) score ≥ 2 were diagnosed with sepsis. The predictive indicators were screened with the least absolute shrinkage and selection operator (LASSO) and collinearity analyses to develop a nomogram. The prediction performance of the new nomogram model, Sequential Organ Failure Assessment (SOFA) score, and Modified Early Warning Score (MEWS) was compared through assessment of the area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI).

Results

The nomogram was based on postoperative heart rate, creatinine concentration, PaO2/FiO2 ratio < 400 mmHg, blood glucose concentration, and international normalized ratio. The AUC of the nomogram, the SOFA score, and MEWS were 0.782 (95% confidence interval CI: 0.716–0.847), 0.649 (95% CI: 0.571–0.727), and 0.541 (95% CI: 0.469–0.614), respectively. The DCA curves showed that the net benefit rate of the nomogram was higher than that of the SOFA score and MEWS. The NRI and IDI tests revealed better predictive performance for the nomogram than SOFA score and MEWS.

Conclusion

Heart rate, creatinine concentration, PaO2/FiO2, glucose concentration, and international normalized ratio should be monitored postoperatively for patients at risk of post-liver transplantation sepsis. The nomogram based on the aforementioned risk factors had a better predictive performance than SOFA score and MEWS.
Outcomes of direct-acting antivirals in patients with HCV decompensated cirrhosis: a systematic review and meta-analysis
Authors: Jongraksak Tanawat , Chuncharunee Alan , Intaraprasong Pongphob , Tansawet Amarit , Thakkinstian Ammarin , Sobhonslidsuk Abhasnee
Published: November 2023

Background

Direct-acting antivirals (DAA) are effective for chronic hepatitis C virus (HCV) treatment. However, their impact on overall survival (OS), hepatocellular carcinoma (HCC) occurrence, HCC-free survival, and liver function in patients with HCV decompensated cirrhosis remains uncertain. This study aimed to evaluate the effects of DAA treatment on this population.

Methods

Studies were identified by searching the MEDLINE, SCOPUS, and CENTRAL databases. OS and HCC-free survival probabilities and time data were extracted from Kaplan-Meier curves. A one-stage meta-analysis using parametric Weibull regression was conducted to estimate the relative treatment effects of DAA vs. no DAA. The primary outcome was the OS rate. The secondary outcomes were HCC-free survival, HCC occurrence rate, and improvement in the Model for End-stage Liver Disease (MELD) score.

Results

Eight cohorts comprising 3,430 participants (2,603 in the DAA group and 1,999 in the no-DAA group) were included. The OS probabilities at 12 and 24 months were 95 and 90% for the DAA group, respectively, compared with 89 and 80% in the no-DAA group, respectively. Hazard ratio (HR) was 0.48 (95% confidence interval (CI): 0.39, 0.60; p < 0.001). The HCC-free survival probabilities at 12 and 24 months were 96 and 90%, respectively, in the former, and 94 and 85%, respectively, in the latter. The HR of HCC occurrence was 0.72 (95% CI: 0.52, 1.00; p = 0.05), which suggests that DAA treatment in decompensated cirrhosis may lead to a 28% lower risk of HCC occurrence. The mean MELD score difference was −7.75 (95% CI: −14.52, −0.98; p = 0.02).

Conclusion

Improvement in OS and MELD score is a long-term benefit of DAA treatment in patients with HCV decompensated cirrhosis, with a marginal effect of the treatment on HCC development.
Impact of wet-lab protocols on quality of whole-genome short-read sequences from foodborne microbial pathogens
Authors: Forth Leonie F. , Brinks Erik , Denay Grégoire , Fawzy Ahmad , Fiedler Stefan , Fuchs Jannika , Geuthner Anne-Catrin , Hankeln Thomas , Hiller Ekkehard , Murr Larissa , Petersen Henning , Reiting Ralf , Schäfers Christian , Schwab Claudia , Szabo Kathrin , Thürmer Andrea , Wöhlke Anne , Fischer Jennie , Lüth Stefanie , Projahn Michaela , Stingl Kerstin , Borowiak Maria , Deneke Carlus , Malorny Burkhard , Uelze Laura
Published: November 2023

For successful elucidation of a food-borne infection chain, the availability of high-quality sequencing data from suspected microbial contaminants is a prerequisite. Commonly, those investigations are a joint effort undertaken by different laboratories and institutes. To analyze the extent of variability introduced by differing wet-lab procedures on the quality of the sequence data we conducted an interlaboratory study, involving four bacterial pathogens, which account for the majority of food-related bacterial infections: Campylobacter spp., Shiga toxin-producing Escherichia coli, Listeria monocytogenes, and Salmonella enterica. The participants, ranging from German federal research institutes, federal state laboratories to universities and companies, were asked to follow their routine in-house protocols for short-read sequencing of 10 cultures and one isolated bacterial DNA per species. Sequence and assembly quality were then analyzed centrally. Variations within isolate samples were detected with SNP and cgMLST calling. Overall, we found that the quality of Illumina raw sequence data was high with little overall variability, with one exception, attributed to a specific library preparation kit. The variability of Ion Torrent data was higher, independent of the investigated species. For cgMLST and SNP analysis results, we found that technological sequencing artefacts could be reduced by the use of filters, and that SNP analysis was more suited than cgMLST to compare data of different contributors. Regarding the four species, a minority of Campylobacter isolate data showed the in comparison highest divergence with regard to sequence type and cgMLST analysis. We additionally compared the assembler SPAdes and SKESA for their performance on the Illumina data sets of the different species and library preparation methods and found overall similar assembly quality metrics and cgMLST statistics.
Oral microbiome alterations in epilepsy and after seizure control
Authors: Lian Xiaolei , Liu Zhenguo , Wu Tianwen , Lou Jiamin , Chen Yuan , Liu Shanshuo , Jin Limin , Li Shuang , Lian Yajun , Jiang Yan , Ren Zhigang
Published: November 2023

Background

The existing diagnostic methods of epilepsy such as history collection and electroencephalogram have great limitations in practice, so more reliable and less difficult diagnostic methods are needed.

Methods

By characterizing oral microbiota in patients diagnosed with epilepsy (EPs) and patients whose seizures were under control (EPRs), we sought to discover biomarkers for different disease states. 16S rRNA gene sequencing was performed on 480 tongue swabs [157 EPs, 22 EPRs, and 301 healthy controls (HCs)].

Results

Compared with normal individuals, patients with epilepsy exhibit increased alpha diversity in their oral microbiota, and the oral microbial communities of the two groups demonstrate significant beta diversity differences. EPs exhibit a significant increase in the abundance of 26 genera, including Streptococcus, Granulicatella, and Kluyvera, while the abundance of 14 genera, including Peptostreptococcus, Neisseria, and Schaalia, is significantly reduced. The area under the receiver operating characteristic curve (AUC) of oral microbial markers in the training cohort and validation cohort was 98.85% and 97.23%, respectively. Importantly, the AUC of the biomarker set achieved 92.44% of additional independent validation sets. In addition, EPRs also have their own unique oral community.

Conclusion

This study describes the characterization of the oral microbiome in EP and EPR and demonstrates the potential of the specific microbiome as a non-invasive diagnostic tool for epilepsy.
Physiology governing diatom vs. dinoflagellate bloom and decline in coastal Santa Monica Bay
Authors: Ollison Gerid A. , Hu Sarah K. , Hopper Julie V. , Stewart Brittany P. , Beatty Jennifer L. , Caron David A.
Published: November 2023

Algal blooms on the Southern California coast are typically dominated by diatom and dinoflagellate taxa, and are governed by their physiological responses to environmental cues; however, we lack a predictive understanding of the environmental controls underlying the establishment and persistence of these distinct bloom events. In this study, we examined gene expression among the numerically dominant diatom and dinoflagellate taxa during spring upwelling bloom events to compare the physiological underpinnings of diatom vs. dinoflagellate bloom dynamics. Diatoms, which bloomed following upwelling events, expressed genes related to dissolved inorganic nitrogen utilization, and genes related to the catabolism of chitin that may have prolonged their bloom duration following nitrogen depletion. Conversely, dinoflagellates bloomed under depleted inorganic nitrogen conditions, exhibited less variation in transcriptional activity, and expressed few genes associated with dissolved inorganic nutrients during their bloom. Dinoflagellate profiles exhibited evidence of proteolysis and heterotrophy that may have enabled them to bloom to high abundances under depleted inorganic nutrients. Taken together, diatom and dinoflagellate transcriptional profiles illustrated guild-specific physiologies that are tuned to respond to and thrive under distinct environmental “windows of opportunity.”
Time-resolved transcriptomic and proteomic profiling of Heyndrickxia coagulans during NaOH-buffered L-lactic acid production
Authors: Huang Xing , Tian Wenzhe , Wang Xiuwen , Qin Jiayang
Published: November 2023

The L-lactic acid (L-LA) fermentation process, based on sodium hydroxide neutralization, demonstrates environmental friendliness during product extraction. However, lactate fermentation is hindered by the pronounced stress effect of sodium lactate on the strain compared with calcium lactate. In this study, we performed time-resolved transcriptomic and proteomic analyses of Heyndrickxia coagulans DSM1 during NaOH-buffered L-LA production. The expression levels of the glycolytic genes demonstrated an initial increase followed by a subsequent decrease, whereas the tricarboxylic acid cycle genes exhibited an initial decrease followed by a subsequent increase throughout the fermentation process. Moreover, we identified clusters of genes consisting of transcription factors and ATP-binding cassette (ABC) transporters that demonstrate a progressive elevation of expression levels throughout the fermentation process, with significant upregulation observed at later stages. This investigation yields valuable insights into the response mechanisms of H. coagulans during NaOH-buffered L-LA fermentation and presents potential targets for metabolic engineering.
Association between gene expression and altered resting-state functional networks in type 2 diabetes
Authors: Zhang Yang , Du Xin , Qin Wen , Fu Yumeng , Wang Zirui , Zhang Quan
Published: November 2023

Background

Type 2 diabetes (T2DM) is a polygenic metabolic disorder that accelerates brain aging and harms cognitive function. The underlying mechanism of T2DM-related brain functional changes has not been clarified.

Methods

Resting-fMRI data were obtained from 99 T2DM and 109 healthy controls (HCs). Resting-state functional connectivity networks (RSNs) were separated using the Independent Component Analysis (ICA) method, and functional connectivity (FC) differences between T2DM patients and HCs within the RSNs were detected. A partial least squares (PLS) regression was used to test the relation between gene expression from Allen Human Brain Atlas (AHBA) and intergroup FC differences within RSNs. Then the FC differences-related gene sets were enriched to determine the biological processes and pathways related to T2DM brain FC changes.

Result

The T2DM patients showed significantly increased FC in the left middle occipital gyrus (MOG) of the precuneus network (PCUN) and the right MOG / right precuneus of the dorsal attention network (DAN). FC differences within the PCUN were linked with the expression of genes enriched in the potassium channel and TrkB-Rac1 signaling pathways and biological processes related to synaptic function.

Conclusion

This study linked FC and molecular alterations related to T2DM and suggested that the T2DM-related brain FC changes may have a genetic basis. This study hoped to provide a unique perspective to understand the biological substrates of T2DM-related brain changes.
Genome-wide association study in Alzheimer’s disease: a bibliometric and visualization analysis
Authors: Zhang Junyao , Wang Yinuo , Zhang Yingying , Yao Junyan
Published: November 2023

Background

Thousands of research studies concerning genome-wide association studies (GWAS) in Alzheimer’s disease (AD) have been published in the last decades. However, a comprehensive understanding of the current research status and future development trends of GWAS in AD have not been clearly shown. In this study, we tried to gain a systematic overview of GWAS in AD by bibliometric and visualization analysis.

Methods

The literature search terms are: (“genome-wide analysis” or “genome-wide association study” or “whole-genome analysis”) AND (“Alzheimer’s Disease” or “Alzheimer Disease”). Relevant publications were extracted from the Web of Science Core Collection (WoSCC) database. Collected data were further analyzed using VOSviewer, CiteSpace and R package Bibliometrix. The countries, institutions, authors and scholar collaborations were investigated. The co-citation analysis of publications was visualized. In addition, research hotspots and fronts were examined.

Results

A total of 1,350 publications with 59,818 citations were identified. The number of publications and citations presented a significant rising trend since 2013. The United States was the leading country with an overwhelming number of publications (775) and citations (42,237). The University of Washington and Harvard University were the most prolific institutions with 101 publications each. Bennett DA was the most influential researcher with the highest local H-index. Neurobiology of Aging was the journal with the highest number of publications. Aβ, tau, immunity, microglia and DNA methylation were research hotspots. Disease and causal variants were research fronts.

Conclusion

The most frequently studied AD pathogenesis and research hotspots are (1) Aβ and tau, (2) immunity and microglia, with TREM2 as a potential immunotherapy target, and (3) DNA methylation. The research fronts are (1) looking for genetic similarities between AD and other neurological diseases and syndromes, and (2) searching for causal variants of AD. These hotspots suggest noteworthy directions for future studies on AD pathogenesis and genetics, in which basic research regarding immunity is promising for clinical conversion. The current under-researched directions are (1) GWAS in AD biomarkers based on large sample sizes, (2) studies of causal variants of AD, and (3) GWAS in AD based on non-European populations, which need to be strengthened in the future.
Kale improves bowel movements in constipated women and affects some intestinal microbes and metabolites: a pilot study
Authors: Nishimoto Yuichiro , Salim Felix , Yamauchi Yohsuke , Mori Yuka , Murakami Shinnosuke , Suzuki Asahi , Fukuda Shinji , Yamada Takuji
Published: November 2023

Dietary fiber improves intestinal environments, by, among others, increasing stool frequency. Kale is a good source of dietary fiber and minerals; however, the effects of kale on the intestinal environment have not yet been evaluated. This study determined how the intestinal environment, including the intestinal microbiota and its metabolome, and stool frequency are affected by the consumption of kale, in humans. A randomized controlled crossover trial, with a 4-week consumption of kale or control food, was conducted. An integrated analysis of the intestinal microbiota and metabolome was performed, and their relationship with improvements in stool frequency was analyzed. Kale intake for 4 weeks significantly increased stool frequency and altered some intestinal microbes, such as an increase in the [Eubacterium] eligens group and a decrease in the [Ruminococcus] gnavus group. Analysis of subjects with increased stool frequency revealed that this group had smaller amounts of stool before kale intake. Our findings indicate that kale modifies certain gut microbes, such as [Eubacterium] eligens and [Ruminococcus] gnavus, and improves bowel movements, particularly in those with smaller stool amounts.
Common millet and soybean intercropping with bio-fertilizer as sustainable practice for managing grain yield and quality
Authors: Šenk Milena , Simić Milena , Milojković-Opsenica Dušanka , Brankov Milan , Tolimir Miodrag , Kodranov Igor , Dragičević Vesna
Published: November 2023

Climate changes are one of the biggest threats to food security. Sustainable agriculture, focused on eco-friendly practices for highly efficient food production, enables greater resilience and safety. This study experimented on intercropping and bio-fertilizer application as convenient ecological solutions for crop yield stability and quality. The experiment was conducted during 2018 and 2020 with soybean and common millet sown in three sowing patterns: alternating rows, alternating strips 1 (2 rows of soybean + 2 rows of millet), and alternating strips 2 (2 rows of soybean + 4 rows of millet), as well as sole crops (control), with or without a bio-fertilizer Coveron. Grain yield and nutrient grain yield response were calculated through land equivalent ratio (LER) and element-LER (E-LER), while quality was estimated based on the concentration of antioxidants (phytate phosphorus, total phenolic compounds, and yellow pigment) and elements in grains, including potential bio-availability of essential elements. Results revealed LER values to be >1 for all sowing patterns, with the highest one achieved in alternating strips 1 (1.38) together with a greater level of all antioxidants in millet grain. Intercropping significantly enhanced Fe and Mn accumulation in both crops and simultaneously decreased the concentration of potentially toxic elements (Al, Cr) in millet grain. Potential bio-availability of essential elements, expressed through the ratio between phytic acid and Ca, Mg, Fe, and Zn revealed smaller values in intercropped soybean and millet with the bio-fertilizer. The bio-fertilizer also increased the concentration of some micro-elements in millet grain, classifying it as a highly dependent plant to microbial inoculation. Interaction of intercropping and bio-fertilizer was most pronounced for LER, E-LER, and accumulation of Fe and Mn in grains. These results highlighted the benefits of soybean–common millet intercropping, especially in combination with the bio-fertilizer, in light of enhanced land utilization and nutrient absorption, thus increasing the resilience of soybean and millet under dry land conditions and low-input systems toward stability and food security.
Case Report: Remarkable breakthrough: successful treatment of a rare intracranial mesenchymal, FET::CREB fusion-positive tumor treated with patient-tailored multimodal therapy
Authors: D’Antonio Federica , Rossi Sabrina , Giovannoni Isabella , Alaggio Rita , Carai Andrea , Milano Giuseppe M. , Cacchione Antonella , Cancellieri Alessandra , Gessi Marco , Antonelli Manila , Colafati Giovanna S. , Megaro Giacomina , Vennarini Sabina , Mastronuzzi Angela
Published: November 2023

Background

Intracranial mesenchymal tumors are a rare type of neoplasm (0.3% of all soft tissue tumors) characterized by a fusion of a FET family gene (usually EWSR1, rarely FUS) to CREB family genes (CREB1, ATF1, and CREM) with a slow-growing and favorable prognosis. Mesenchymal tumors are most frequently localized in the subcutaneous tissue (typically in the limbs and hands) of young adults and have rarely been diagnosed in the central nervous system. Surgery is the gold standard treatment; adjuvant radiation therapy and chemotherapy with sarcoma-based regimens have been used in rare cases when complete surgical excision was not recommended. In terms of prognosis, these tumors show a tendency for local relapse. The longest patient outcomes reported in the literature are five years.

Case description

This case describes a 27-year-old woman with unconventional extracranial metastatic sites of myxoid intracranial mesenchymal tumor FET::CREB fusion-positive and high expression of PD-1 (40%) and PD-L1 (30%). Based on clinical, molecular, and histological characteristics, she underwent various local and systemic therapies, including surgery, proton beam therapy, the use of immune checkpoint inhibitors, and chemotherapy. These treatments led to a complete remission of the disease after eight years from tumor diagnosis.

Conclusions

Our case sheds light on the importance of precision medicine and tailored therapy to explore new treatment opportunities for rare or unknown tumor entities.
Breastfeeding women in need of information about antiemetics for nausea and vomiting during pregnancy: a review of inquiries to a medicines information service
Authors: Heitmann Kristine , Bakkebø Tina , Havnen Gro C. , Schjøtt Jan
Published: November 2023

Introduction: The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during pregnancy (NVP) or hyperemesis gravidarum (HG). However, treatment guidelines for NVP or HG do not address the use of antiemetics in women who are breastfeeding while becoming pregnant again. Our objective was to characterize inquiries to describe the need for lactation risk information among women with NVP or HG and also to raise awareness of this topic.

Method: We conducted a review of inquiries to the Norwegian web-based medicines information service, SafeMotherMedicine.

Results: In total, 97 inquiries addressing the use of antiemetics for NVP or HG during breastfeeding were identified. The following medications were addressed in the inquiries (n = 97): meclizine (51%), metoclopramide (33%), promethazine (16%), ondansetron (9%), and others (6%). The breastfed child was older than 6 months and 1 year in 96% and 71% of the inquiries, respectively. There was a preponderance of general inquiries (unclear motivation/double checking) (64%); however, one-third of the inquiries were generated by restrictive information from sources such as product information.

Conclusion: Based on our small review of spontaneous inquiries, there seems to be an information need about the use of antiemetics during lactation among women breastfeeding an older infant whilst suffering from NVP or HG. Addressing such use in guidelines for NVP and HG and/or other easily available information sources may be considered in order to balance out the restrictive information provided by the manufacturers. This could avoid potential unnecessary weaning of breastfeeding in an otherwise challenging situation.
Efficacy and safety of pregabalin and gabapentin in spinal stenosis: a systematic review and meta-analysis
Authors: Martínez Telmo , Mariscal Gonzalo , de la Rubia Ortí Jose Enrique , Barrios Carlos
Published: November 2023

Background and Objective: Multimodal management of spinal stenosis is on the rise, and central sensitisation inhibitors are playing an essential role in the treatment of central sensitisation processes. Pregabalin and gabapentin are antiepileptic drugs that decrease presynaptic excitability. The aim of this study was to investigate whether the use of pregabalin and gabapentin is effective in the symptomatic management of spinal stenosis, compared to other drugs, by using pain and disability rating scales. We also assessed the safety profile associated with these drugs.

Methods: We conducted a bibliographic search in the Pubmed, Web of Science, and Cochrane Collaboration Library databases. The inclusion criteria were studies that compared pregabalin or gabapentin to a control group in patients with lumbar spinal stenosis. We included randomized clinical trialsand a comparative retrospective cohort study. The primary clinical endpoints were VAS/NRS and ODI, measured at two, four, 8 weeks, and 3 months, while adverse events and walking distance were also collected. We combined the data using Review Manager 5.4 software.

Results: Our meta-analysis included six studies with a total of 392 patients, with a mean age of 60.3 years. We observed no significant differences in VAS scores at two, four, and 8 weeks: MD: 0.23, 95% CI: 0.63 to 1.09; MD: −0.04, 95% CI: −0.64 to −0.57; and MD: −0.6, 95% CI: −1.22 to 0.02, respectively. However, at 3 months, we found significant differences in favor of pregabalin with respect to VAS: MD: −2.97, 95% CI: −3.43 to −2.51. We did not observe significant differences respect to the ODI: MD: −3.47, 95% CI: −7.15 to −0.21. Adverse events were significantly higher in the pregabalin/gabapentin group (OR 5.88, 95% CI: 1.28–27.05).

Conclusion: Our meta-analysis suggests that abapentinoids may have a significant effect on VAS score at 3 months, but no significant differences were observed in ODI scores, and adverse events were higher in the gabapentinoids group.
ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway
Authors: Peng Zhen , Lv Xiaolong , Wang Xintong , Shang Ting , Chang Jing , Salahdiin Khalid , Guo Yue , Zhang Zhisen , Shen Ru , Lyu Ming , He Shuang , Yang Jian , Wang Yuefei , Gao Xiumei , Zhu Yan , Feng Yuxin
Published: November 2023

Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by a microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) and coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported that ACT001, a modified compound of parthenolide, improved the survival of sepsis mice. In this work, we used cecal ligation and puncture (CLP) model to induce SIC. Transthoracic echocardiography and HE staining assays were adopted to evaluate the influence of ACT001 on sepsis-induced cardiac dysfunction. Our results showed that ACT001 significantly improved heart function and reduced SIC. Coagulation accelerates organ damage in sepsis. We found that ACT001 decreased blood clotting in the FeCl3-induced carotid artery thrombosis experiment. ACT001 also reduced the production of neutrophil extracellular traps (NETs). RNA-sequencing of heart tissues revealed that ACT001 significantly downregulated the expression of pro-inflammatory cytokines and the JAK-STAT signaling pathway. These results were confirmed with real-time PCR and ELISA. In summary, we found ACT001 rescued mice from septic shock by protecting the cardiovascular system. This was partially mediated by inhibiting pro-inflammatory cytokine production and down-regulating the JAK-STAT signaling.
TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter
Authors: Sun Xin , Yang Le , Sun Hui , Sun Ye , Wei Shuyun , Han Ying , Wang Wenkai , Kong Ling , Wang Xijun
Published: November 2023

Gout represents a metabolic ailment resulting from the accumulation of monosodium urate crystals within joints, causing both inflammation and, harm to tissues. The primary contributor to gout’s emergence is an elevated presence of serum urate, which is under the regulation of kidney and, gut urate transporters. Mitigating this risk factor is crucial for averting gout’s onset. Several treatments rooted in TCM and related active compounds have demonstrated efficacy in managing gout, skillfully regulating serum uric acid (UA) levels and curbing inflammation’s progression. This analysis compiles key foundational research concerning the molecular signaling pathways and UA transporters linked to gout, under the regulation of TCM. The focus includes individual botanical drug, active compounds, and TCM formulations, which have been consolidated and examined in this overview. The primary keywords chosen were “gout, hyperuricemia, gouty arthritis, traditional Chinese medicine, Chinese botanical drug, medicinal botanical drug, and natural plant”. Various relevant literature published within the last 5 years were gathered from electronic databases, including PubMed, Web of Science, CNKI, and others. The findings revealed that TCM has the capacity to modulate various signaling pathways, including MAPK, NF-κB, PI3K/Akt, NLRP3 and JAK/STAT. Additionally, it impacts UA transporters like URAT1, GLUT9, ABCG2, as well as OATs and OCTs, thereby contributing to gout treatment. TCM helps maintain a balanced inflammatory interaction and facilitates UA excretion. This study enhances our understanding of TCM’s anti-gout mechanisms and introduces novel perspectives for establishing the clinical significance and future prospects of TCM-based gout treatment.
Sex differences in the factors that affect medical lethality in elderly suicide attempters
Authors: Kim HeungKyu , Min Seongho , Ahn Joung-Sook , Kim Hyun , Cha Yong Sung , Lee Jinhee , Kim Min-Hyuk
Published: November 2023

Objectives

This study aimed to identify sex differences in the factors that affect medical lethality in elderly suicide attempters.

Methods

A total of 253 elderly suicide attempters and 351 middle-aged attempters (comparison group) who visited the emergency room at a general hospital were included. The sociodemographic and clinical characteristics of the patients were investigated. The Chi-squared test and logistic regression analysis were performed. And Spearman’s correlation coefficient was calculated.

Results

In older males, the risk of high lethality was lower when attempting suicide due to the loss of family members [adjusted odds ratio (AOR): 0.08]. The risk increased as the intent to die became more certain (some AOR: 11.31, certain AOR: 28.75), and this association became more pronounced with age (rho middle-aged: 0.329; young-old: 0.387; old-old: 0.415). In older females, the risk was lower when employed (AOR: 0.28). The method of suicide attempt also affected lethality (agricultural chemicals AOR: 3.71; psychiatric medication AOR: 0.31).

Conclusion

Sex differences in the factors that affect medical lethality were identified among elderly suicide attempters. In particular, medical lethality can be predicted by the degree of suicide intention in older males. These findings will help to establish more efficient preventive strategies with specific targets.
Effect of brain acidification on depression-related behaviors in diabetes mellitus
Authors: Temma Yusuke , Obi-Nagata Kisho , Hoshiba Yoshio , Miyake Ryuhei , Katayama Yuta , Hagihara Hideo , Suzuki Norimitsu , Miyakawa Tsuyoshi , Nakayama Keiichi I. , Hayashi-Takagi Akiko
Published: November 2023

Major depressive disorder (depression) is a leading cause of disability. The severity of depression is affected by many factors, one of which being comorbidity with diabetes mellitus (DM). The comorbidity of depression with DM is a major public health concern due to the high incidence of both conditions and their mutually exacerbating pathophysiology. However, the mechanisms by which DM exacerbates depression remain largely unknown, and elucidating these regulatory mechanisms would contribute to a significant unmet clinical need. We generated a comorbid mouse model of depression and DM (comorbid model), which was extensively compared with depression and DM models. Depressive and anhedonic phenotypes were more severe in the comorbid model. We thus concluded that the comorbid model recapitulated exacerbated depression-related behaviors comorbid with DM in clinic. RNA sequencing analysis of prefrontal cortex tissue revealed that the brain pH homeostasis gene set was one of the most affected in the comorbid model. Furthermore, brain pH negatively correlated with anhedonia-related behaviors in the depression and comorbid models. By contrast, these correlations were not detected in DM or control group, neither of which had been exposed to chronic stress. This suggested that the addition of reduced brain pH to stress-exposed conditions had synergistic and aversive effects on anhedonic phenotypes. Because brain pH was strongly correlated with brain lactate level, which correlated with blood glucose levels, these findings highlight the therapeutic importance of glycemic control not only for DM, but also for psychiatric problems in patients with depression comorbid with DM.
Association between Life’s simple 7 and rheumatoid arthritis in adult Americans: data from the National Health and nutrition examination survey
Authors: Wang Jie , Xing Fei , Sheng Ning , Xiang Zhou
Published: November 2023

Objective

The study aimed to investigate the relationship between Life’s Simple 7 (LS7) and the risk of rheumatoid arthritis (RA) in adult Americans.

Methods

A total of 17,532 participants were included in this study. The association between LS7 and the risk of RA was assessed using a weighted logistic regression model, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. Moreover, the nonlinear relationship was further characterized through smooth curve fitting (SCF) and weighted generalized additive model (GAM) analysis.

Results

After adjusting for all covariates, the weighted logistic regression model demonstrated that the LS7 was negatively correlated with the risk of RA. Compared to quintile 1 of LS7, the OR between the risk of RA and quartile 4 of LS7 (LS7.Q4) was 0.261 (95% CI, 0.203, 0.337) in males under 50 years old, while in females of the same age group, the OR was 0.183 (95% CI, 0.142, 0.234). For females aged between 50 and 70 years old, the OR between the risk of RA and LS7.Q4 was 0.313 (95% CI, 0.264, 0.371). In females aged 70 years or older, the OR between the risk of RA and LS7.Q4 was 0.632 (95% CI, 0.486, 0.822).

Conclusion

This finding suggested the healthy lifestyle behaviors represented by LS7 have a negative association with RA. However, further prospective studies are needed to verify the causal relationship in the results.
Promoting physical activity and a healthy active lifestyle in community-dwelling older adults: a design thinking approach for the development of a mobile health application
Authors: Daniels Kim , Lemmens Ryanne , Knippenberg Els , Marinus Nastasia , Vonck Sharona , Baerts Jan , Bergs Jochen , Spooren Annemie , Hansen Dominique , Bonnechère Bruno
Published: November 2023

Background

Physical activity (PA) has wide-ranging, and well documented benefits for older adults, encompassing physical, cognitive, and mental well-being. The World Health Organization advocates for a minimum of 150–300 min of moderate intensity PA per week, supplemented by muscle-strengthening exercises. However, the rates of PA among older adults remain a concern. While portable technologies hold promises in promoting PA, sustaining long-term engagement continues to be a challenge.

Objective

The aims of this study are to identify barriers and facilitators to PA in older adults, to develop an mHealth app promoting PA and an active healthy lifestyle in collaboration with community-dwelling older adults guided by the design thinking process, and to test it.

Methods

A co-creative process was used, employing design thinking. Interviews were conducted to understand the needs of the target population and identify the problem of insufficient PA. Two cocreation sessions involving older adults and experts were conducted to generate innovative ideas. Participants were selected based on age (≥65 years), no severe illness, Dutch language proficiency, and active participation ability. Results were qualitatively analyzed and coded. Finally a prototype was developed and tested.

Results

Interviews with older adults highlighted diverse perceptions of PA but unanimous agreement on its importance. They recognized health benefits such as improved mobility, balance, and reduced fall risk, while emphasizing the social and mental aspects. Barriers included poor health, time constraints, weather conditions and fear of falling. Cocreation sessions identified key topics: perception of a healthy lifestyle, coping strategies, mHealth App features, screen visualization, and tailored notifications, which led to the development of a mobile app promoting PA and an active lifestyle. The app was stepwise prototyped.

Conclusion

This study emphasizes the importance of promoting PA among older adults through a collaborative design thinking approach. However, the implementation of mHealth apps faces obstacles due to the digital divide, necessitating personalized solutions to bridge the gap. Moreover, it calls for further research to investigate the long-term impact of such interventions and explore behavior change patterns in this population.