bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroinflammation, autoinflammation, splenomegaly and anemia caused by bi-allelic mutations in IRAK4
Authors: Cooray Samantha , Price-Kuehne Fiona , Hong Ying , Omoyinmi Ebun , Burleigh Alice , Gilmour Kimberly C. , Ahmad Bilal , Choi Sangdun , Bahar Mohammad W. , Torpiano Paul , Gagunashvili Andrey , Jensen Barbara , Bellos Evangelos , Sancho-Shimizu Vanessa , Herberg Jethro A. , Mankad Kshitij , Kumar Atul , Kaliakatsos Marios , Worth Austen J. J. , Eleftheriou Despina , Whittaker Elizabeth , Brogan Paul A.
Published: September 2023

We describe a novel, severe autoinflammatory syndrome characterized by neuroinflammation, systemic autoinflammation, splenomegaly, and anemia (NASA) caused by bi-allelic mutations in IRAK4. IRAK-4 is a serine/threonine kinase with a pivotal role in innate immune signaling from toll-like receptors and production of pro-inflammatory cytokines. In humans, bi-allelic mutations in IRAK4 result in IRAK-4 deficiency and increased susceptibility to pyogenic bacterial infections, but autoinflammation has never been described. We describe 5 affected patients from 2 unrelated families with compound heterozygous mutations in IRAK4 (c.C877T (p.Q293*)/c.G958T (p.D320Y); and c.A86C (p.Q29P)/c.161 + 1G>A) resulting in severe systemic autoinflammation, massive splenomegaly and severe transfusion dependent anemia and, in 3/5 cases, severe neuroinflammation and seizures. IRAK-4 protein expression was reduced in peripheral blood mononuclear cells (PBMC) in affected patients. Immunological analysis demonstrated elevated serum tumor necrosis factor (TNF), interleukin (IL) 1 beta (IL-1β), IL-6, IL-8, interferon α2a (IFN-α2a), and interferon β (IFN-β); and elevated cerebrospinal fluid (CSF) IL-6 without elevation of CSF IFN-α despite perturbed interferon gene signature. Mutations were located within the death domain (DD; p.Q29P and splice site mutation c.161 + 1G>A) and kinase domain (p.Q293*/p.D320Y) of IRAK-4. Structure-based modeling of the DD mutation p.Q29P showed alteration in the alignment of a loop within the DD with loss of contact distance and hydrogen bond interactions with IRAK-1/2 within the myddosome complex. The kinase domain mutation p.D320Y was predicted to stabilize interactions within the kinase active site. While precise mechanisms of autoinflammation in NASA remain uncertain, we speculate that loss of negative regulation of IRAK-4 and IRAK-1; dysregulation of myddosome assembly and disassembly; or kinase active site instability may drive dysregulated IL-6 and TNF production. Blockade of IL-6 resulted in immediate and complete amelioration of systemic autoinflammation and anemia in all 5 patients treated; however, neuroinflammation has, so far proven recalcitrant to IL-6 blockade and the janus kinase (JAK) inhibitor baricitinib, likely due to lack of central nervous system penetration of both drugs. We therefore highlight that bi-allelic mutation in IRAK4 may be associated with a severe and complex autoinflammatory and neuroinflammatory phenotype that we have called NASA (neuroinflammation, autoinflammation, splenomegaly and anemia), in addition to immunodeficiency in humans.
A response-surface approach into the interactive effects of multiple stressors reveals new insights into complex responses
Authors: Brooks Paul R. , Browne Mark Anthony , Benedetti-Cecchi Lisandro , Lyons Devin A. , Crowe Tasman P.
Published: September 2023

Understanding the difficult to predict interactive effects of anthropogenic stressors is recognized as one of the major challenges facing environmental scientists and ecosystem managers. Despite burgeoning research, predicting stressor interactions is still difficult, in part because the same two stressors can interact, or not, depending on their intensities. While laboratory experiments have provided useful insights about how organisms respond to serial doses of single stressors, we lack ‘response-surface’ field experiments in which naturally occurring assemblages are exposed to multiple types and concentrations of stressors. Here we used a field-based dosing system combined with a ‘response-surface’ design to test the individual and combined effects of two stressors (copper and chlorpyrifos) at five concentrations of each, for a total of 25 replicated treatments (n=4). After six weeks of dosing, chemical uptake and impacts at several levels of biological organization in mussel assemblages were measured. Stressor combinations produced interactive effects that would not have been revealed without using this replicated ‘response-surface approach’. Results show that non-additive effects of multiple stressors may be more complex and more common than previously thought. Additionally, our findings suggest that interactive effects of multiple stressors vary across levels of organization which has implications for monitoring and managing the chemical, biological and ecological impacts of priority pollutants in the real world.
Global trends in the research of biodegradable biomedical magnesium-based materials: a bibliometric analysis
Authors: Zhu Yi , Liu Yuezhu , Wu Lanping , Yang Qian
Published: September 2023

Background: In recent years, there has been a notable surge in the interest surrounding biodegradable materials, particularly in the context of biomedical applications. This has led to a significant rise in the number of research studies focusing on the utilization of biodegradable magnesium-based materials in the field of biomedicine. However, a dearth of comprehensive assessment exists regarding the body of research concerning biodegradable biomedical magnesium-based materials. In this study, a bibliometric approach was used to illustrate the current state of research and global trends pertaining to biodegradable magnesium-based materials for biomedical applications.

Methods: We conducted a search of the Web of Science core collection database for the past decade (2013–2022). VOSviewer software and the bibliometric online analysis platform were employed for bibliometric analysis and visualization.

Results: Correspondingly, 1267 documents were retrieved. We discovered that the number of papers in the field of degradable biomedical magnesium-based materials research has increased annually. In addition, China and the Chinese Academy of Sciences have published the largest number of papers in the field of biodegradable biomedical magnesium-based materials. Papers related to biodegradable magnesium-based materials for biomedical use were mainly published in acta biomaterialia, materials science and engineering c-materials for biological applications and materials journals. Keyword co-occurrence analysis showed that “corrosion"and “mechanical-properties” appear more frequently. The top 10 common keywords include corrosion, mechanical-properties, microstructure, biocompatibility, behavior, magnesium, magnesium alloys, degradation magnesium alloy, in vitro.

Conclusion: Research on biodegradable magnesium-based materials for biomedical use continues to increase steadily. China maintains a leading position in the world, and the Chinese Academy of Sciences represents a notable contribution to the research of biodegradable magnesium-based materials for biomedical use. Subsequently, “corrosion” and “mechanical-properties” were identified as the current research hotspots in the area of biodegradable biomedical magnesium-based materials.
Feasibility of the preparation of cochleate suspensions from naturally derived phosphatidylserines
Authors: Kristensen Søren , Hassan Khadeija , Andersen Nadia Skarnager , Steiniger Frank , Kuntsche Judith
Published: September 2023

Introduction

Cochleates are cylindrical particles composed of dehydrated phospholipid bilayers. They are typically prepared by addition of calcium ions to vesicles composed of negatively charged phospholipids such as phosphatidylserines (PS). Due to their high physical and chemical stability, they provide an interesting alternative over other lipid-based drug formulations for example to improve oral bioavailability or to obtain a parenteral sustained-release formulation.

Methods

In the present study, the feasibility to prepare cochleate suspensions from soy lecithin-derived phosphatidylserines (SPS) was investigated and compared to the “gold standard” dioleoyl-phosphatidylserine (DOPS) cochleates. The SPS lipids covered a large range of purities between 53 and >96% and computer-controlled mixing was evaluated for the preparation of the cochleate suspensions. Electron microscopic investigations were combined with small-angle x-ray diffraction (SAXD) and Laurdan generalized polarization (GP) analysis to characterize particle structure and lipid organization.

Results

Despite some differences in particle morphology, cochleate suspensions with similar internal lipid structure as DOPS cochleates could be prepared from SPS with high headgroup purity (≥96%). Suspensions prepared from SPS with lower purity still revealed a remarkably high degree of lipid dehydration and well-organized lamellar structure. However, the particle shape was less defined, and the typical cochleate cylinders could only be detected in suspensions prepared with higher amount of calcium ions. Finally, the study proves the feasibility to prepare suspensions of cochleates or cochleate-like particles directly from a calcium salt of soy-PS by dialysis.
Different responses of soil fungal and bacterial communities to nitrogen addition in a forest grassland ecotone
Authors: Li Daiyan , Meng Meng , Ren Baihui , Ma Xinwei , Bai Long , Li Jiahuan , Bai Guohua , Yao Fengjun , Tan Chunming
Published: September 2023

Introduction

Continuous nitrogen deposition increases the nitrogen content of terrestrial ecosystem and affects the geochemical cycle of soil nitrogen. Forest-grassland ecotone is the interface area of forest and grassland and is sensitive to global climate change. However, the structure composition and diversity of soil microbial communities and their relationship with soil environmental factors at increasing nitrogen deposition have not been sufficiently studied in forest-grassland ecotone.

Methods

In this study, experiments were carried out with four nitrogen addition treatments (0 kgN·hm−2·a−1, 10 kgN·hm−2·a−1, 20 kgN·hm−2·a−1 and 40 kgN·hm−2·a−1) to simulate nitrogen deposition in a forest-grassland ecotone in northwest Liaoning Province, China. High-throughput sequencing and qPCR technologies were used to analyze the composition, structure, and diversity characteristics of the soil microbial communities under different levels of nitrogen addition.

Results and discussion

The results showed that soil pH decreased significantly at increasing nitrogen concentrations, and the total nitrogen and ammonium nitrogen contents first increased and then decreased, which were significantly higher in the N10 treatment than in other treatments (N:0.32 ~ 0.48 g/kg; NH4+-N: 11.54 ~ 13 mg/kg). With the increase in nitrogen concentration, the net nitrogen mineralization, nitrification, and ammoniation rates decreased. The addition of nitrogen had no significant effect on the diversity and structure of the fungal community, while the diversity of the bacterial community decreased significantly at increasing nitrogen concentrations. Ascomycetes and Actinomycetes were the dominant fungal and bacterial phyla, respectively. The relative abundance of Ascomycetes was negatively correlated with total nitrogen content, while that of Actinomycetes was positively correlated with soil pH. The fungal community diversity was significantly negatively correlated with nitrate nitrogen, while the diversity of the bacterial community was significantly positively correlated with soil pH. No significant differences in the abundance of functional genes related to soil nitrogen transformations under the different treatments were observed. Overall, the distribution pattern and driving factors were different in soil microbial communities in a forest-grassland ecotone in northwest Liaoning. Our study enriches research content related to factors that affect the forest-grassland ecotone.
A cross-sectional study on the nasopharyngeal microbiota of individuals with SARS-CoV-2 infection across three COVID-19 waves in India
Authors: Bose Tungadri , Wasimuddin  , Acharya Varnali , Pinna Nishal Kumar , Kaur Harrisham , Ranjan Manish , SaiKrishna Jandhyala , Nagabandi Tulasi , Varma Binuja , Tallapaka Karthik Bharadwaj , Sowpati Divya Tej , Haque Mohammed Monzoorul , Dutta Anirban , Siva Archana Bharadwaj , Mande Sharmila S.
Published: September 2023

Background

Multiple variants of the SARS-CoV-2 virus have plagued the world through successive waves of infection over the past three years. Independent research groups across geographies have shown that the microbiome composition in COVID-19 positive patients (CP) differs from that of COVID-19 negative individuals (CN). However, these observations were based on limited-sized sample-sets collected primarily from the early days of the pandemic. Here, we study the nasopharyngeal microbiota in COVID-19 patients, wherein the samples have been collected across the three COVID-19 waves witnessed in India, which were driven by different variants of concern.

Methods

The nasopharyngeal swabs were collected from 589 subjects providing samples for diagnostics purposes at the Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India and subjected to 16s rRNA gene amplicon - based sequencing.

Findings

We found variations in the microbiota of symptomatic vs. asymptomatic COVID-19 patients. CP showed a marked shift in the microbial diversity and composition compared to CN, in a wave-dependent manner. Rickettsiaceae was the only family that was noted to be consistently depleted in CP samples across the waves. The genera Staphylococcus, Anhydrobacter, Thermus, and Aerococcus were observed to be highly abundant in the symptomatic CP patients when compared to the asymptomatic group. In general, we observed a decrease in the burden of opportunistic pathogens in the host microbiota during the later waves of infection.

Interpretation

To our knowledge, this is the first analytical cross-sectional study of this scale, which was designed to understand the relation between the evolving nature of the virus and the changes in the human nasopharyngeal microbiota. Although no clear signatures were observed, this study shall pave the way for a better understanding of the disease pathophysiology and help gather preliminary evidence on whether interventions to the host microbiota can help in better protection or faster recovery.
Uniformly shaped harmonization combines human transcriptomic data from different platforms while retaining their biological properties and differential gene expression patterns
Authors: Borisov Nicolas , Tkachev Victor , Simonov Alexander , Sorokin Maxim , Kim Ella , Kuzmin Denis , Karademir-Yilmaz Betul , Buzdin Anton
Published: September 2023

Introduction: Co-normalization of RNA profiles obtained using different experimental platforms and protocols opens avenue for comprehensive comparison of relevant features like differentially expressed genes associated with disease. Currently, most of bioinformatic tools enable normalization in a flexible format that depends on the individual datasets under analysis. Thus, the output data of such normalizations will be poorly compatible with each other. Recently we proposed a new approach to gene expression data normalization termed Shambhala which returns harmonized data in a uniform shape, where every expression profile is transformed into a pre-defined universal format. We previously showed that following shambhalization of human RNA profiles, overall tissue-specific clustering features are strongly retained while platform-specific clustering is dramatically reduced.

Methods: Here, we tested Shambhala performance in retention of fold-change gene expression features and other functional characteristics of gene clusters such as pathway activation levels and predicted cancer drug activity scores.

Results: Using 6,793 cancer and 11,135 normal tissue gene expression profiles from the literature and experimental datasets, we applied twelve performance criteria for different versions of Shambhala and other methods of transcriptomic harmonization with flexible output data format. Such criteria dealt with the biological type classifiers, hierarchical clustering, correlation/regression properties, stability of drug efficiency scores, and data quality for using machine learning classifiers.

Discussion: Shambhala-2 harmonizer demonstrated the best results with the close to 1 correlation and linear regression coefficients for the comparison of training vs validation datasets and more than two times lesser instability for calculation of drug efficiency scores compared to other methods.
Template MRI scans reliably approximate individual and group-level tES and TMS electric fields induced in motor and prefrontal circuits
Authors: Cho Jennifer Y. , Van Hoornweder Sybren , Sege Christopher T. , Antonucci Michael U. , McTeague Lisa M. , Caulfield Kevin A.
Published: September 2023

Background

Electric field (E-field) modeling is a valuable method of elucidating the cortical target engagement from transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), but it is typically dependent on individual MRI scans. In this study, we systematically tested whether E-field models in template MNI-152 and Ernie scans can reliably approximate group-level E-fields induced in N = 195 individuals across 5 diagnoses (healthy, alcohol use disorder, tobacco use disorder, anxiety, depression).

Methods

We computed 788 E-field models using the CHARM–SimNIBS 4.0.0 pipeline with 4 E-field models per participant (motor and prefrontal targets for TMS and tES). We additionally calculated permutation analyses to determine the point of stability of E-fields to assess whether the 152 brains represented in the MNI-152 template is sufficient.

Results

Group-level E-fields did not significantly differ between the individual vs. MNI-152 template and Ernie scans for any stimulation modality or location (p > 0.05). However, TMS-induced E-field magnitudes significantly varied by diagnosis; individuals with generalized anxiety had significantly higher prefrontal and motor E-field magnitudes than healthy controls and those with alcohol use disorder and depression (p < 0.001). The point of stability for group-level E-field magnitudes ranged from 42 (motor tES) to 52 participants (prefrontal TMS).

Conclusion

MNI-152 and Ernie models reliably estimate group-average TMS and tES-induced E-fields transdiagnostically. The MNI-152 template includes sufficient scans to control for interindividual anatomical differences (i.e., above the point of stability). Taken together, using the MNI-152 and Ernie brains to approximate group-level E-fields is a valid and reliable approach.
Comparison of auditory brainstem response and electrocochleography to assess the coupling efficiency of active middle ear implants
Authors: Gawliczek Tom , Mantokoudis Georgios , Anschuetz Lukas , Caversaccio Marco D. , Weder Stefan
Published: September 2023

Aim

This study aimed to compare the effectiveness of auditory brainstem response (ABR) and extracochlear electrocochleography (ECochG) in objectively evaluating the coupling efficiency of floating mass transducer (FMT) placement during active middle ear implant (AMEI) surgery.

Methods

We enrolled 15 patients (mean age 58.5 ± 19.4 years) with mixed hearing loss who underwent AMEI implantation (seven ossicular chain and eight round window couplings). Before the surgical procedure, an audiogram was performed. We utilized a clinical measurement system to stimulate and record intraoperative ABR and ECochG recordings. The coupling efficiency of the VSB was evaluated through ECochG and ABR threshold measurements. Postoperatively, we conducted an audiogram and a vibrogram.

Results

In all 15 patients, ABR threshold testing successfully determined intraoperative coupling efficiency, while ECochG was successful in only eight patients. In our cohort, ABR measurements were more practical, consistent, and robust than ECochG measurements. Coupling efficiency, calculated as the difference between vibrogram thresholds and postoperative bone conduction thresholds, was found to be more accurately predicted by ABR measurements (p = 0.016, R2 = 0.37) than ECochG measurements (p = 0.761, R2 = 0.02). We also found a non-significant trend toward better results with ossicular chain coupling compared to round window coupling.

Conclusion

Our findings suggest that ABR measurements are more practical, robust, and consistent than ECochG measurements for determining coupling efficiency during FMT placement surgery. The use of ABR measurements can help to identify the optimal FMT placement, especially with round window coupling. Finally, we offer normative data for both techniques, which can aid other clinical centers in using intraoperative monitoring for AMEI placement.
Cancer-associated fibroblasts in hematologic malignancies: elucidating roles and spotlighting therapeutic targets
Authors: Ding Ziyang , Shi Run , Hu Weikang , Tian Lei , Sun Rong , Wu Yang , Zhang Xiaoyan
Published: September 2023

Hematologic malignancies comprise a diverse range of blood, bone marrow, and organ-related disorders that present significant challenges due to drug resistance, relapse, and treatment failure. Cancer-associated fibroblasts (CAFs) represent a critical component of the tumor microenvironment (TME) and have recently emerged as potential therapeutic targets. In this comprehensive review, we summarize the latest findings on the roles of CAFs in various hematologic malignancies, including acute leukemia, multiple myeloma, chronic lymphocytic leukemia, myeloproliferative neoplasms, and lymphoma. We also explore their involvement in tumor progression, drug resistance, and the various signaling pathways implicated in their activation and function. While the underlying mechanisms and the existence of multiple CAF subtypes pose challenges, targeting CAFs and their associated pathways offers a promising avenue for the development of innovative treatments to improve patient outcomes in hematologic malignancies.
Pan-cancer analysis identified OAS1 as a potential prognostic biomarker for multiple tumor types
Authors: Jiang Shan , Deng Xinzhou , Luo Ming , Zhou Le , Chai Jingjing , Tian Chao , Yan Yutao , Luo Zhiguo
Published: September 2023

Background

2’,5’-oligoadenylate synthetase 1 (OAS1), has been reported as a tumor driver gene in breast carcinoma and pancreatic carcinoma. However, the role of OAS1 in most tumors has not been reported.

Methods

The original data of 35 tumor types were down load from the TCGA (The Cancer Genome Atlas) database and Human Protein Atlas (HPA) database. TIMER2, Kmplot, UALCAN, and TISIDB tools were used to investigate the expression and function of OAS1, and the role of OAS1 in prognosis, diagnostic value, and immune characteristics of pan-cancer. LUAD and PRAD cell lines, A549, H1975, PC-3 and C4-2 were utilized to perform cell function tests.

Results

OAS1 expression was up-regulated in 12 tumor types and down-regulated in 2 tumor types. High OAS1 expression was correlated with poor prognosis in 6 tumor types, while high OAS1 expression was correlated with good prognosis in 2 tumor types. OAS1 was correlated with molecular subtypes in 8 tumor types and immune subtypes in 12 tumor types. OAS1 was positively associated with the expression of numerous immune checkpoint genes and tumor mutational burden (TMB). OAS1 had potential diagnostic value in 15 tumor types. Silence of OAS1 significantly inhibited the cell proliferation ability, and promoted G2/M cell cycle arrest of LUAD and PRAD cells. Meanwhile, silence of OAS1 enhanced cisplatin-induced apoptosis of LUAD and PRAD cells, but weakened cell migration.

Conclusion

This pan-cancer study suggests that OAS1can be used as a molecular biomarker for prognosis in pan-cancer and may play an important role in tumor immune response.
Combining stereotactic body radiotherapy with immunotherapy in stage IV non-small cell lung cancer
Authors: Liu Xiaoli , Chi Alexander
Published: September 2023

Immunotherapy has revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC). Oligometastasis has been associated with better prognosis than widespread metastatic disease and may be curable by stereotactic body radiotherapy (SBRT). SBRT can stimulate immunogenic anti-tumor activity, which can be further augmented when combined with immunotherapy, such as immune checkpoint inhibitors (ICIs). Thus, its combination with immunotherapy was recognized as a promising treatment option, especially in the metastatic setting. However, the most optimal approach to combine SBRT with immunotherapy remains controversial with early clinical evidence emerging. Here, we review the current clinical evidence supporting the combination of SBRT with immunotherapy in the treatment of metastatic NSCLC. Also, we discuss the current controversies and areas for further exploration associated with this treatment strategy.
Breastfeeding vs. breast milk transmission during COVID-19 pandemic, which is more important?
Authors: He Yan-fei , Liu Jun-qiang , Hu Xiao-dong , Li Hu-ming , Wu Ni , Wang Jie , Jiang Zhi-gang
Published: September 2023

The catastrophic coronavirus disease 2019 (COVID-19) pandemic has raised many health questions, and whether breast milk from SARS-CoV-2 infected mothers may be a vector for SARS-CoV-2 transmission has become a hot topic of concern worldwide. Currently, there are extremely limited and conflicting data on the risk of infection in infants through breastfeeding. For this reason, we investigated almost all current clinical studies and systematically analyzed the presence of SARS-CoV-2 and antibodies in the breast milk of mothers infected with SARS-CoV-2, their effects on newborns, and the mechanisms involved. A total of 82 studies were included in this review, of which 66 examined the presence of SARS-CoV-2 in breast milk samples from mothers diagnosed with COVID-19, 29 reported results of antibody detection of SARS-CoV-2 in breast milk, and 13 reported both nucleic acid and antibody test results. Seventeen studies indicated the presence of detectable SARS-CoV-2 nucleic acid in breast milk samples, and only two studies monitored viral activity, both of which reported that infectious viruses could not be cultured from RNA-positive breast milk samples. All 29 studies indicated the presence of at least one of the three antibodies, IgA, IgG and IgM, in breast milk. Five studies indicated the presence of at least one antibody in the serum of breastfed newborns. No COVID-19-related deaths were reported in all 1,346 newborns. Our study suggests that direct breastfeeding does not pose an additional risk of infection to newborns and that breast milk is a beneficial source of anti-SARS-CoV-2 antibodies that provide passive immune protection to infants. In addition, direct breastfeeding would provide maternal benefits. Our review supports the recommendation to encourage direct breastfeeding under appropriate infection control guidelines.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier: 458043.
Chronic jet lag reduces motivation and affects other mood-related behaviors in male mice
Authors: Acosta Julieta , Crespo Manuel T. , Plano Santiago A. , Golombek Diego A. , Chiesa Juan J. , Agostino Patricia V.
Published: September 2023

Introduction: The circadian system regulates various physiological processes such as sleep-wake cycles, hormone secretion, metabolism, and the reaction to both natural and drug-based rewards. Chronic disruption of the circadian system caused by unsteady synchronization with light-dark (LD) schedules, such as advancing chronic jet lag (CJL), leads to adverse physiological effects and pathologies, and is linked with changes in mood and depressive behaviors in humans and rodent models.

Methods: C57BL/6J male mice were subjected to circadian disruption through phase advances of 6 h every 2 days (CJL +6/2). Mice under 12:12-h LD cycle were used as controls. After 8 weeks under these conditions, a battery of behavioral tests was performed to assess if mood-related behaviors were affected.

Results: Compared to controls under 24 h LD cycles, mice under CJL presented desynchronization of activity-rest rhythms that led to several behavioral impairments, including a decrease in motivation for food reward, and an increase in anxiety, anhedonia, and depressive-like behavior.

Conclusion: Chronic circadian disruption, caused by an experimental CJL protocol, affects mood-related and reward-related behaviors in mice. Understanding the importance of the circadian system and its potential role for disruption due to CJL is important for maintaining good health and well-being.
Genetic diversity and population structure analyses in barley (Hordeum vulgare) against corn-leaf aphid, Rhopalosiphum maidis (Fitch)
Authors: Maanju Sunny , Jasrotia Poonam , Yadav Surender Singh , Sharma Preeti , Kashyap Prem Lal , Kumar Sudheer , Jat Manoj Kumar , Singh Gyanendra Pratap
Published: September 2023

Corn-leaf aphid (CLA), Rhopalosiphum maidis (Fitch) (Hemiptera: Aphididae) is a serious economic pest of barley worldwide. Breeding for aphid resistance in plants is considered a cost-effective and environmentally safe approach for aphid control, compared to the use of chemical pesticides. One of the challenges in breeding for aphid resistance is the identification of resistant plant genotypes, which can be achieved through the use of molecular markers. In the present study, a set of aphid specific 10 simple-sequence repeats (SSR) markers were used to investigate genetic diversity and population structure analyses in 109 barley genotypes against R. maidis. Three statistical methods viz., multivariate hierarchical clustering based on Jaccard’s similarity coefficient, principal coordinate analysis (PCoA) and the Bayesian approach were utilized to classify the 109 barley genotypes. The analyses revealed four subpopulations i.e., SubPop1, SubPop2, SubPop3 and SubPop4 with 19, 46, 20 and 24 genotypes including admixtures, respectively and represented 17.43%, 42.2%, 18.34% and 22.01% genotypes of the total population size, respectively. The studied SSR markers produced 67 polymorphic bands, with an average of 6.7 and ranging from 3 to 12 bands. Heterozygosity (H) was found to be highest in SSR28 (0.64) and lowest in SSR27 (0.89). The observed genetic diversity index varied from 0.10 to 0.34 (with an average of 0.19). Major allele frequency varied from 74.08% to 94.80%. On an average, 87.52% of the 109 barley genotypes shared a common major allele at any locus. Based on the Aphid Infestation Index (AII), only 2 genotypes were found to be resistant against CLA. SubPop2 also had lowest mean aphid population (28.83), widest genetic similarity index (0.60-1.00) and highest genetic similarity coefficient (0.82), which highlighted its potential for inclusion in future CLA resistance breeding programs.
Investigating the dynamic responses of Aegilops tauschii Coss. to salinity, drought, and nitrogen stress: a comprehensive study of competitive growth and biochemical and molecular pathways
Authors: Hameed Rashida , Abbas Adeel , Saeed Muhammad , Shahani Aitezaz A. A. , Huang Ping , Du Daolin , Zulfiqar Usman , Alamri Saud , Alfagham Alanoud T.
Published: September 2023

Aegilops tauschii (Coss.) is a highly deleterious, rapidly proliferating weed within the wheat, and its DD genome composition exhibits adaptability toward diverse abiotic stresses and demonstrates heightened efficacy in nutrient utilization. Current study investigated different variegated impacts of distinct nitrogen concentrations with varied plant densities, scrutinizing the behavior of Ae. tauschii under various salinity and drought stress levels through multiple physiological, biochemical, and molecular pathways. Different physiological parameters attaining high growth with different plant density and different nitrogen availability levels increased Ae. tauschii dominancy. Conversely, under the duress of salinity and drought, Ae. tauschii showcased an enhanced performance through a comprehensive array of physiological and biochemical parameters, including catalase, peroxidase, malondialdehyde, and proline content. Notably, salinity-associated traits such as sodium, potassium, and the sodium–potassium ratio exhibited significant variations and demonstrated remarkable tolerance capabilities. In the domain of molecular pathways, the HKT and DREB genes have displayed a remarkable upregulation, showcasing a comparatively elevated expression profile in reaction to different levels of salinity and drought-induced stress. Without a doubt, this information will make a substantial contribution to the understanding of the fundamental behavioral tendencies and the efficiency of nutrient utilization in Ae. tauschii. Moreover, it will offer innovative viewpoints for integrated management, thereby enabling the enhancement of strategies for adept control and alleviation.
Reliability and validity of the Chinese post-discharge coping difficulty scale-parent form in parents of premature infants: a multicenter cross-sectional study
Authors: Liu Jin , Gong Jingjing , Shen Qingqing , Si Zaixia , Gao Jianli , Xu Leijie , Liu Xiaoqin , Song Yayun , Li Minmin
Published: September 2023

Background

The measurement of the coping difficulties of parents of premature infants after discharge provides objective data for nurses to prepare infants for discharge. However, no Chinese scale has been developed to measure parents’ coping difficulties after their premature infants are discharged.

Aim

To translate the parent version of the Post-Discharge Coping Difficulty Scale (Ped-PDCDS) from English to Chinese and test the reliability and validity of the Chinese version in parents of premature infants.

Methods

A multicenter cross-sectional study of 356 parents of premature infants was conducted. The scale was symmetrically translated. Validity was evaluated in terms of content, construct, discriminant, and convergent validities. Reliability was assessed in terms of internal consistency, split-half reliability, and test–retest reliability.

Results

The Chinese Ped-PDCDS finally contained 11 items. Exploratory and confirmatory factor analyses results showed that the Chinese Ped-PDCDS had three dimensions, and the convergent and discriminant validities of the scale was satisfactory. The overall reliability, split-half reliability, and test–retest reliability of the scale was 0.85, 0.92, and 0.84, respectively.

Conclusion

The Chinese Ped-PDCDS has adequate psychometric properties, and is an easy and appropriate instrument for measuring parents’ difficulty in coping with premature infants.
Cannabis use during pregnancy and hemodynamic responses to infant cues in pregnancy: an exploratory study
Authors: Powers Shannon , Han Xu , Martinez Jacqueline , Dufford Alexander John , Metz Torri D. , Yeh Tom , Kim Pilyoung
Published: September 2023

Introduction

Cannabis is one of the most commonly used substances during pregnancy and has the potential to negatively impact parent-infant relationships. The prefrontal cortex (PFC) response to infant cues during pregnancy has been associated with subsequent positive parenting behaviors. However, PFC activation is altered in individuals who use cannabis. As the potency of cannabis has changed over the years, little is known about the specific role of cannabis use on gestational parent brain responses to infant cues.

Materials and methods

Using functional Near-Infrared Spectroscopy (fNIRS) in the second trimester of pregnancy, we measured hemodynamic responses to an infant cry task and an infant faces task among individuals who were using cannabis (N = 14) and compared them with those who were not using cannabis (N = 45). For the infant cry task, pregnant individuals listened to cry sounds and matched white noise. For the infant faces task, they viewed happy, sad, and neutral faces.

Results

There was no significant difference between the two groups after adjusting for multiple comparisons. Without adjusting for multiple comparisons, we found preliminary evidence for the differences in the dorsomedial PFC associated with heightened response to infant cry among individuals who use cannabis. The groups were also different in the dorsolateral PFC associated with decreased response to infant sad faces among individuals who use cannabis.

Discussion

Our preliminary data suggests that cannabis use during pregnancy was associated with brain activation in the regions involved in the emotional regulation and information processes. However, the results did not survive after adjustment for multiple comparisons, thus future research with larger sample sizes is needed to confirm potential differences in brain function among cannabis-using pregnant individuals.
Effectiveness and cost-effectiveness of six GLP-1RAs for treatment of Chinese type 2 diabetes mellitus patients that inadequately controlled on metformin: a micro-simulation model
Authors: Yuan Shuai , Wu Yingyu
Published: September 2023

Objective

To systematically estimate and compare the effectiveness and cost-effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) approved in China and to quantify the relationship between the burden of diabetic comorbidities and glycosylated hemoglobin (HbA1c) or body mass index (BMI).

Methods

To estimate the costs (US dollars, USD) and quality-adjusted life years (QALY) for six GLP-1RAs (exenatide, loxenatide, lixisenatide, dulaglutide, semaglutide, and liraglutide) combined with metformin in the treatment of patients with type 2 diabetes mellitus (T2DM) which is inadequately controlled on metformin from the Chinese healthcare system perspective, a discrete event microsimulation cost-effectiveness model based on the Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model was developed. A cohort of 30,000 Chinese patients was established, and one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) with 50,000 iterations were conducted considering parameter uncertainty. Scenario analysis was conducted considering the impacts of research time limits. A network meta-analysis was conducted to compare the effects of six GLP-1RAs on HbA1c, BMI, systolic blood pressure, and diastolic blood pressure. The incremental net monetary benefit (INMB) between therapies was used to evaluate the cost-effectiveness. China’s per capita GDP in 2021 was used as the willingness-to-pay threshold. A generalized linear model was used to quantify the relationship between the burden of diabetic comorbidities and HbA1c or BMI.

Results

During a lifetime, the cost for a patient ranged from USD 42,092 with loxenatide to USD 47,026 with liraglutide, while the QALY gained ranged from 12.50 with dulaglutide to 12.65 with loxenatide. Compared to exenatide, the INMB of each drug from highest to lowest were: loxenatide (USD 1,124), dulaglutide (USD −1,418), lixisenatide (USD −1,713), semaglutide (USD −4,298), and liraglutide (USD −4,672). Loxenatide was better than the other GLP-1RAs in the base-case analysis. Sensitivity and scenario analysis results were consistent with the base-case analysis. Overall, the price of GLP-1RAs most affected the results. Medications with effective control of HbA1c or BMI were associated with a significantly smaller disease burden (p < 0.05).

Conclusion

Loxenatide combined with metformin was identified as the most economical choice, while the long-term health benefits of patients taking the six GLP-1RAs are approximate.
Growth and rupture of an intracranial aneurysm: the role of wall aneurysmal enhancement and CD68+
Authors: Cannizzaro Delia , Zaed Ismail , Olei Simone , Fernandes Bethania , Peschillo Simone , Milani Davide , Cardia Andrea
Published: September 2023

Introduction

Intracranial aneurysms occur in 3%–5% of the general population. While the precise biological mechanisms underlying the formation, growth, and sudden rupture of intracranial aneurysms remain partially unknown, recent research has shed light on the potential role of inflammation in aneurysm development and rupture. In addition, there are ongoing investigations exploring the feasibility of employing new drug therapies for controlling the risk factors associated with aneurysms. CD68, a glycosylated glycoprotein and the human homolog of macrosialin, is prominently expressed in monocyte/macrophages within inflamed tissues and has shown potential application in oncology. An observational study was conducted with the aim of comparing the histological characteristics of aneurysm walls with preoperative MRI scans, specifically focusing on CD68 activity.

Method

An observational pilot study was conducted to investigate the histological characteristics of the aneurysm wall that could be potentially associated with aneurysm growth and rupture. A total of 22 patients diagnosed with ruptured and unruptured intracranial aneurysms who had undergone conventional clipping between January 2017 and December 2022 were included in the study.

Results

A histopathological analysis of the aneurysm wall was performed in all patients, particularly focusing on the presence of CD68. A preoperative MRI with gadolinium was conducted in 10 patients with unruptured aneurysms and six patients with ruptured aneurysms. An emergency clipping was performed in the remaining six patients. The results showed that CD68 positivity and wall enhancement were significantly associated with intracranial aneurysm wall degeneration, growth, and rupture.

Conclusion

The histological and radiological inflammatory findings observed in the wall of cerebral aneurysms, as well as the CD68 positivity, are significantly associated with the risk of intracranial aneurysm growth and rupture. This study highlights the crucial importance of considering clinical and medical data when making treatment decisions for intracranial aneurysms. Furthermore, it emphasizes the relevance of evaluating wall enhancement in MRI scans as part of the diagnostic and prognostic process.
Infrared thermography as a non-invasive method for evaluating stress in lactating dairy cows during isolation challenges
Authors: Mincu Madalina , Nicolae Ioana , Gavojdian Dinu
Published: September 2023

The overall objective of the current data report was to evaluate and test the feasibility of using infrared thermography (IRT) as a non-invasive method for measuring stress signs in lactating dairy cows during short negative challenges, such as visual isolation from herd-mates. The study was carried out at the Experimental Farm of the Research and Development Institute for Bovine Romania, on 20 Holstein-Friesian lactating multiparous dairy cows, between August and September 2022. Cows were housed in two identical tied stanchion barns (170/85 cm), and were isolated individually from the herd for 240 min post-morning milking. Our results shown significant (p ≤ 0.05) rises for both orbital and nasal IRT temperatures following the isolation challenge, suggesting that such approaches could represent adequate tools for assessing social stress in cattle. Overall, current results are in accordance with previous studies which validated both eye and nasal regions as IRT thermal windows for studying the effects of painful and negative contexts on stress response in farmed ruminants, while considering the stress-induced hyperthermia as an integral part of the physiological response to negative stimuli, as well as the current limitations that this tool faces.
Potential Use of Phosphate-Solubilizing Bacteria in Soybean Culture
Authors: Silvestrini Gabriel Rieth , da Rosa Elton José , Corrêa Henrique Cunha , Dal Magro Taísa , Silvestre Wendel Paulo , Pauletti Gabriel Fernandes , Conte Elaine Damiani
Published: September 2023

Using microorganisms to enhance crop productivity is an active and increasing field of research, which encompasses the productive, environmental, and economic aspects of agricultural production to obtain high-quality crops with a reduction in the need for fertilizers. Among the nutrients necessary for plant growth, phosphorous is problematic due to its low availability and its susceptibility to convert into non-labile forms. In this regard, phosphate-solubilizing bacteria (PSB) can be an interesting tool to improve phosphorous availability and to reduce the requirements of phosphate fertilizers. This work aimed to evaluate the potential use of phosphate-solubilizing bacteria in the supply of phosphorus and soybean development. This study was conducted in the 2019/2020 and 2020/2021 harvests. The experimental design was in randomized blocks, containing seven treatments and six replicates. The treatments consisted of five doses of phosphate fertilization, using triple superphosphate fertilizer, associated with the application of Bacillus subtilis and Bacillus megaterium bacteria, and two treatments, with and without the use of phosphorous fertilizer and without the use of an inoculant. Plant tissue nutrients and biometric and productive parameters of the crop were assessed. According to the observed results, applying PSB associated with phosphate fertilization and phosphate fertilization alone did not influence soybean’s nutritional, biometric, and productive parameters in the two harvests. Thus, the application of B. subtilis and B. megaterium, either associated or not associated with phosphate fertilization, does not contribute to the nutrition, development, and yield of soybean crops in soil with a naturally low P content, considering the climatic and soil conditions of the study.
Antibody Titer Prediction from Serum Immunodiffusion Test of Patients with Paracoccidioidomycosis Using Infrared Spectroscopy and Chemometrics
Authors: Koehler Alessandra , Scroferneker Maria Lúcia , de Moraes Paulo Cezar , Pereira Beatriz Aparecida Soares , Cavalcante Ricardo de Souza , Mendes Rinaldo Pôncio , Corbellini Valeriano Antonio
Published: September 2023

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi of the genus Paracoccidioides. Serological tests are auxiliary in the diagnosis of PCM. However, the lack of standardization is a central problem in serodiagnosis and antibody titration. The objective of this study was to propose a methodology based on Fourier transform infrared spectroscopy (FTIR) for predicting antibody titers in patients with PCM. A total of 118 serum samples from patients with PCM were included, for which antibody titration using double immunodiffusion (DID) was previously performed. Serum samples were analyzed by attenuated total reflection (ATR)-FTIR and a supervised analysis with partial least squares regression (PLS) was used to predict the antibody titers. The PLS model with two latent variables and with the use of one orthogonal signal correction (OSC) showed a determination coefficient (R2) higher than 0.9999 for both the calibration and prediction set. The model was able to predict the antibody titers from patients with PCM with a minimal error. Therefore, modeling with FTIR/ATR and multivariate calibration proved to be a fast and highly accurate method for antibody titration, replacing the need for antigen production and performance of traditional serological tests.