bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the stability of the reference genes GAPDH, SDHA and RPL-19 in sheep from a semi-arid region infected by gastrointestinal nematodes
Authors: Lucas Nascimento Souza Jorge , Cavalcante Silva Fernanda , da Silva Carlikelly Gleicy , Maria Fortaleza Neves Bomfim Isabela , Rocha de Medeiros Henrique , Giotto Zaros Lilian
Published: September 2023

Analyzing the stability of reference genes already described as universal is an important methodology to lead gene expression analysis because different studies have shown that the expression of universal reference genes may vary between experimental treatments. In this sense, the glyceraldehyde 3-phosphate dehydrogenase (GAPDH), Succinate dehydrogenase complex subunit A (SDHA) and Ribosomal Protein L-19 (RPL-19) reference genes (already described in other studies with sheep from different regions, breeds and infectious agents or in organisms evolutionarily close to sheep) were investigated in the abomasum, small and large intestines of resistant and susceptible crossbred sheep groups to gastrointestinal nematode infections in the Semi-arid region in Northeast of Brazil. The animals were naturally infected to determine the resistance or susceptibility status by counting eggs per gram (EPG) of feces from the gastrointestinal tract after 33 weeks of observations of infection evolution. Relative gene expression was performed by RT-qPCR methodology using Sybr green and relative gene expression stability was tested by different software programs such as REST, BestKeeper, geNorm and Normfinder. Our results showed the susceptible animals had increase in egg counts per gram of feces than resistant animals (p < 0.001), and both groups showed a mixed infection by nematodes of the genus Haemonchus, Trichostrongylus, Oesophagostomum and Trichuris. Furthermore, we show the importance of analyzing different genes in different software programs and the importance to choose ideal reference genes. In this sense, GAPDH was the most stable gene in the abomasum, whereas SDHA was the most stable in the small and large intestines. In addition, we discuss about variables which can interfere in relative expression such as breed, species, climate and tissue. However, utilizing other reference genes already described in other studies with the same and different variables should be performed.
Epidemiological and clinical characteristics of psittacosis among cases with complicated or atypical pulmonary infection using metagenomic next-generation sequencing: a multi-center observational study in China
Authors: Huang Weifeng , Wang Fengge , Cai Qingqing , Xu Huiliang , Hong Dengwei , Wu Han , Zhou Lu , Hu Linjie , Lu Yihan
Published: September 2023

Background

Chlamydia psittaci (C. psittaci) causes parrot fever in humans. Development of metagenomic next-generation sequencing (mNGS) enables the identification of C. psittaci.

Methods

This study aimed to determine the epidemiological and clinical characteristics of parrot fever cases in China. A multi-center observational study was conducted in 44 tertiary and secondary hospitals across 14 provinces and municipalities between April 2019 and October 2021.

Results

A total of 4545 patients with complicated or atypical pulmonary infection were included in the study, among which the prevalence of C. psittaci was determined to be 2.1% using mNGS. The prevalence of C. psittaci was further determined across demographic groups and types of specimens. It was significantly higher in patients with senior age (2.6% in those > 50 years), winter-spring (3.6%; particularly in December, January, and February), and southwestern (3.4%) and central and southern China (2.7%) (each P < 0.001). Moreover, the prevalence was the highest in bronchoalveolar lavage fluid (BALF) (2.9%), compared with sputum (1.1%) and peripheral blood specimens (0.9%). Additionally, co-infection of principal microorganisms was compared. Certain microorganisms were more likely to co-infect in parrot fever cases, such as Candida albicans in BALF (26.7%) and peripheral blood (6.3%), compared with non-parrot fever cases (19.7% and 1.3%); however, they did not significantly differ (each P > 0.05).

Conclusion

Parrot fever remains low in patients with complicated or atypical pulmonary infection. It is likely to occur in winter-spring and southwestern region in China. BALF may be the optimal specimen in the application of mNGS. Co-infection of multiple microorganisms should be further considered.
Emergence of carbapenem-resistant enterobacterales co-harboring blaOXA−78 and blaOXA−58 from India
Authors: Das Bhaskar Jyoti , Singha K. Melson , Wangkheimayum Jayalaxmi , Chanda Debadatta Dhar , Bhattacharjee Amitabha
Published: September 2023

Background

Carbapenem-Resistant Enterobacterales (CRE) has been categorized as pathogens of critical priority by World Health organization (WHO) as they pose significant threat to global public health. Carbapenemase production considered as the principal resistance mechanism against carbapenems and with the recent surge and expansion of carbapenemases and its variants among clinically significant bacteria in India, the present study reports expansion blaOXA−78 and blaOXA−58 of in CRE of clinical origin.

Methods

Bacterial isolates were collected from a tertiary referral hospital and identified through VITEK® 2 Compact automated System (Biomerieux, France). Rapidec® Carba NP (Biomerieux, France) was used to investigate carbapenemase production followed by antibiotic susceptibility testing through Kirby-Bauer Disc Diffusion method and agar dilution method. Class D carbapenemase genes were targeted through PCR assay followed by investigation of horizontal transmission of blaOXA−58 and blaOXA−78. Whole genome sequencing was carried out using Illumina platform to investigate the genetic context of blaOXA−58 and blaOXA−78 genes and further characterization of the CRE isolates.

Results

The carbapenem-resistant Escherichia coli (BJD_EC456) and Serratia marcescens (BJD_SM81) received during the study from the tertiary referral hospital were isolated from sputum and blood samples respectively. PCR assay followed by whole genome sequencing revealed that the isolates co-harbor blaOXA−58 and blaOXA−78, a variant of blaOXA−51. Horizontal transfer of blaOXA−58 and blaOXA−78 genes were unsuccessful as these genes were located on the chromosome of the study isolates. Transposon Tn6080 was linked to blaOXA−78 in the upstream region while the insertion sequences ISAba26 and ISCfr1 were identified in the upstream and downstream region of blaOXA−58 gene respectively. In addition, both the isolates were co-harboring multiple antibiotic resistance genes conferring clinical resistance towards beta-lactams, aminoglycosides, fluroquinolones, sulphonamides, tetracyclines. BJD_EC180 belonged to ST2437 while BJD_SM81 was of an unknown sequence type. The nucleotide sequences of blaOXA−78 (OQ533021) and blaOXA−58 (OQ533022) have been deposited in GenBank.

Conclusions

The study provides a local epidemiological information regarding carbapenem resistance aided by transposon and insertion sequences associated blaOXA−78 and blaOXA−58 genes associated and warrants continuous monitoring to prevent their further dissemination into carbapenem non-susceptible strains thereby contributing to carbapenem resistance burden which is currently a global concern.
Antileukemic effect of venetoclax and hypomethylating agents via caspase-3/GSDME-mediated pyroptosis
Authors: Ye Fanghua , Zhang Wen , Fan Chenying , Dong Jiajia , Peng Min , Deng Wenjun , Zhang Hui , Yang Liangchun
Published: September 2023

Background

The identifying of B-cell lymphoma 2 (Bcl-2) as a therapeutic target has led to a paradigm shift in acute myeloid leukemia (AML) treatment. Pyroptosis is a novel antitumor therapeutic mechanism due to its cytotoxic and immunogenic effects. The combination of venetoclax and hypomethylating agents (HMAs) has been shown to lead to durable responses and significantly improve prognosis in patients with AML. However, our understanding of the mechanisms underlying this combinatorial activity is evolving.

Methods

We investigated whether the Bcl-2 inhibitor venetoclax induces AML cell pyroptosis and identified pyroptosis effector proteins. Via using western blotting, immunoprecipitation, RNA interference, CCK8 assays, and LDH assays, we explored the mechanism underlying the pyroptotic effect. The relationship between the expression of the pyroptosis effector protein GSDME and AML prognosis was investigated. The effect of GSDME demethylation combined with venetoclax treatment on pyroptosis was investigated and confirmed in mouse models and clinical samples.

Results

Venetoclax induces pyroptosis that is mediated by caspase-3-dependent GSDME cleavage. Mechanistically, venetoclax upregulates caspase-3 and GSDME cleavage by activating the intrinsic apoptotic pathway. GSDME is downregulated in AML by promoter methylation, and low GSDME expression is significantly associated with poor prognosis, based on public databases and patient sample analysis. In vivo and in vitro experiments showed that GSDME overexpression or HMAs-mediated restoration of GSDME expression significantly increased venetoclax-induced pyroptosis in AML.

Conclusion

GSDME-mediated pyroptosis may be a novel aspect of the antileukemic effect of Bcl-2 inhibitors. This finding offers new insights into potential biomarkers and therapeutic strategies, identifying an important mechanism explaining the clinical activity of venetoclax and HMAs in AML.
Diagnostic value of cerebrospinal fluid Neutrophil Gelatinase-Associated Lipocalin for differentiation of bacterial meningitis from tuberculous meningitis or cryptococcal meningitis: a prospective cohort study
Authors: Wang Qi , Lin Qingwen , Wang Haiyan , Tang Minjie , Fan Kengna , Zhang Zeqin , Huang Er , Zhang Weiqing , Wang Fengqing , Ou Qishui , Liu Xiaofeng
Published: September 2023

Background

The early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM) remains a significant clinical challenge. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been reported as a novel inflammatory biomarker in the early stages of infection. This study aimed to investigate whether cerebrospinal fluid (CSF) NGAL can serve as a potential biomarker for distinguishing between BM and TBM or CM.

Methods

We prospectively enrolled the patients with suspected CNS infections at admission and divided them into three case groups: BM (n = 67), TBM (n = 55), CM (n = 51), and an age- and sex-matched hospitalized control (HC, n = 58). Detected the CSF NGAL and assessed its diagnostic accuracy in distinguishing between BM and TBM or CM. Additionally, longitudinally measured the CSF NGAL levels in patients with BM to evaluate its potential as a monitoring tool for antibacterial treatment.

Results

The concentration of CSF NGAL in BM was significantly higher than in TBM, CM, and HC (allP < 0.05), while the serum NGAL did not show significant differences among the three case groups. The ROC analysis demonstrated that CSF NGAL presented a good diagnostic performance with an AUC of 0.834 (0.770–0.886) and at the optimal cutoff value of 74.27 ng/mL with 70.15% sensitivity and 77.36% specificity for discriminating BM with TBM and CM. Additionally, the CSF NGAL in the convalescent period of BM was significantly lower than in the acute period (P < 0.05).

Conclusions

CSF NGAL may serve as a potential biomarker for distinguishing between acute BM and TBM or CM. Additionally, it holds clinical significance in monitoring the effectiveness of antibiotic therapy for BM.
Effect of acceptance and commitment therapy for depressive disorders: a meta-analysis
Authors: Zhao Bing , Wang Qian , Wang Liping , Chen Jie , Yin Tongtong , Zhang Jingxuan , Cheng Xiaojing , Hou Ruihua
Published: September 2023

Objective

To systematically evaluate the effect of Acceptance and Commitment Therapy (ACT) on depressive disorders.

Methods

The electronic databases of Web of Science Core Collection, Pubmed, EMBASE, Cochrane Library, PsycInfo, CNKI, Wanfang and Weipu were used to select relevant publications. Screening, data extraction, and quality assessment were undertaken following PRISMA guidelines for preferred reporting of systematic reviews and meta-analysis. RevMan5.4 was used for meta-analysis.

Results

11 studies with a total of 962 patients were included. Random-effects model analysis showed that ACT could effectively reduce the level of depressive symptoms in patients with depressive disorders (SMD = − 1.05, 95% CI: − 1.43–− 0.66, P < 0.00001), improve psychological flexibility (MD = 4.84, 95% CI: 2.70–6.97, P < 0.00001), and have good maintenance effect (SMD = − 0.70, 95% CI: − 1.15–− 0.25, P = 0.002). All differences were statistically significant.

Conclusions

ACT not only improves depressive symptoms and psychological flexibility, but also has a good maintenance effect, and it is particularly effective in Chinese patients. Large randomized controlled trials are needed to validate the findings from this meta-analysis.
“The chameleon among diseases” - an explorative view of sarcoidosis and identification of the consequences for affected patients and relatives using qualitative interviews
Authors: Hilker Charlotte , Weis Johanna , Ziehfreund Stefanie , Arkema Elizabeth V. , Biedermann Tilo , Zink Alexander
Published: September 2023

Introduction

Sarcoidosis is a multisystemic disease, with the lungs being the main site of manifestation. Although the exact etiology remains unclear, both genetic and environmental factors are being discussed. Diagnostic evaluation is challenging, and the management of chronic patients and assessment of their needs proves difficult, especially in the absence of targeted therapy. Studies on sarcoidosis patients have shown that quality of life is limited even after clinically measurable parameters have resolved. The question remains how patients and their relatives perceive medical care and the diagnostic process and how these affect their well-being.

Methods

Qualitative, semi-structured interviews were conducted with patients and their relatives between September 2019 and February 2020. Interviews were recorded, transcribed verbatim, and analyzed using qualitative content analysis. Deductive hypotheses were then formed based on categories according to personal aspects, symptoms, diagnostic, daily life activity, therapy, psychological aspects and wishes.

Results

Fourteen patients and five relatives were included. Most patients reported subacute symptoms before the first organ-related episode. A high degree of personal initiative was required from the majority of respondents in both the diagnostic and subsequent therapeutic processes. In addition, respondents reported so-called “doctor-hopping”, a lack of specialists or contacts, and a lack of medical support. The Internet and self-help groups played a fundamental role for patients and relatives in exchanging information with other affected persons and to compensate for an existing information deficit.

Conclusion

The results provide new insights into patients’ and relatives’ perceptions of the sarcoidosis diagnosis and treatment process. Identification of barriers such as a lack of physicians and an information deficit highlights potential targets for strategies to optimize sarcoidosis management.
Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours
Authors: Nabbi Arash , Beck Pengbo , Delaidelli Alberto , Oldridge Derek A. , Sudhaman Sumedha , Zhu Kelsey , Yang S. Y. Cindy , Mulder David T. , Bruce Jeffrey P. , Paulson Joseph N. , Raman Pichai , Zhu Yuankun , Resnick Adam C. , Sorensen Poul H. , Sill Martin , Brabetz Sebastian , Lambo Sander , Malkin David , Johann Pascal D. , Kool Marcel , Jones David T. W. , Pfister Stefan M. , Jäger Natalie , Pugh Trevor J.
Published: September 2023

Background

Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers.

Methods

To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets.

Results

Within pedNST, we uncovered four broad immune clusters: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%) and Immune Desert (17%). We validated these clusters using immunohistochemistry, methylation immune inference and segmentation analysis of tissue images. We report shared biology of these immune clusters within and across cancer types, and characterization of specific immune cell frequencies as well as T- and B-cell repertoires. We found no associations between immune infiltration levels and tumour mutational burden, although molecular cancer entities were enriched within specific immune clusters.

Conclusions

Given the heterogeneity of immune infiltration within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies.
Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study
Authors: Wang Can , Sun Wenyan , Dalbeth Nicola , Wang Zhongjun , Wang Xuefeng , Ji Xiaopeng , Xue Xiaomei , Han Lin , Cui Lingling , Li Xinde , Liu Zhen , Ji Aichang , He Yuwei , Sun Mingshu , Li Changgui
Published: September 2023

Background

Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied.

Objectives

This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate.

Methods

A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 μmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints.

Results

Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups.

Conclusion

The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT.

Trial registration

This project was registered in ChiCTR (www.chictr.org.cn), with the registration number: ChiCTR2100050749.
Production of highly immunogenic and safe Triton X-100 produced bacterial ghost vaccine against Shigella flexneri 2b serotype
Authors: Abdelfattah Amany , Samir Reham , Amin Heba M.
Published: September 2023

Background

Bacterial ghost cells (BGCs) are cells were drained of their genetic and cytoplasmic components. This work aimed to develop vaccine candidates against the Shigella flexneri (S. flexneri) 2b serotype using the BGCs approach. For the first time, (S. flexneri) 2b serotype BGCs vaccine was prepared by incubation with Triton X-100 (TX100) for only 12 h. Its safety and immunogenicity were compared to another vaccine produced using a previously used surfactant, namely Tween 80 (TW80). Scanning electron microscopy (SEM), cellular DNA, protein contents measurements, and ghost cell re-cultivation were used to confirm the successful generation of the BGCs. Immunogenicity was assessed through mice's intraperitoneal (IP) immunization followed by infection with S. flexneri ATCC 12022. Finally, histopathological examination was carried out.

Results

Viable colony forming units (CFUs) of S. flexneri were counted from stool samples as well as homogenized colon tissues of the non-immunized challenged group. Immunized mice sera showed a significant increase in serum bactericidal activity of both preparations (TX100 = 40% and TW80 = 56%) compared to the non-immunized challenged group (positive control). The IgG levels of the bacterial ghost-vaccinated groups were four and three times greater for the TX100 and TW80 ghost vaccines, respectively, compared to that of the positive control; both bacterial ghost vaccines (BGVs) were safe and effective, according to the results of the safety check tests and histopathological analysis.

Conclusions

When comparing the BGVs prepared using TX100 and TW80 methods, the use of TX100 as a new chemical treating agent for BGC production attained robust results in terms of shorter incubation time with the targeted cells and a strong immune response against S. flexneri 2b serotype ATCC 12022 in the IP challenge test. However, a clinical study is needed to confirm the efficacy and total safety of this novel vaccine.
Pictorial essay: MRI evaluation of endometriosis-associated neoplasms
Authors: Radzynski Louise , Boyer Louis , Kossai Myriam , Mouraire Anne , Montoriol Pierre-François
Published: September 2023

Endometriosis is a frequent pathology mostly affecting women of young age. When typical aspects are present, the diagnosis can easily be made at imaging, especially at MRI. Transformation of benign endometriosis to endometriosis-associated neoplasms is rare. The physiopathology is complex and remains controversial. Endometrioid carcinoma and clear cell carcinoma are the main histological subtypes. Our goal was to review the main imaging characteristics that should point to an ovarian or extra-ovarian endometriosis-related tumor, especially at MRI, as it may be relevant prior to surgical management.

Key points

• Transformation of benign endometriosis to endometriosis-associated neoplasms is rare.

• MRI is useful when displaying endometriosis lesions associated to an ovarian tumor.

• Subtraction imaging should be used in the evaluation of complex endometriomas.
Sex-biased gene and microRNA expression in the developing mouse brain is associated with neurodevelopmental functions and neurological phenotypes
Authors: Szakats Susanna , McAtamney Alice , Cross Hugh , Wilson Megan J.
Published: September 2023

Background

Sex differences pose a challenge and an opportunity in biomedical research. Understanding how sex chromosomes and hormones affect disease-causing mechanisms will shed light on the mechanisms underlying predominantly idiopathic sex-biased neurodevelopmental disorders such as ADHD, schizophrenia, and autism. Gene expression is a crucial conduit for the influence of sex on developmental processes; therefore, this study focused on sex differences in gene expression and the regulation of gene expression. The increasing interest in microRNAs (miRNAs), small, non-coding RNAs, for their contribution to normal and pathological neurodevelopment prompted us to test how miRNA expression differs between the sexes in the developing brain.

Methods

High-throughput sequencing approaches were used to identify transcripts, including miRNAs, that showed significantly different expression between male and female brains on day 15.5 of development (E15.5).

Results

Robust sex differences were identified for some genes and miRNAs, confirming the influence of biological sex on RNA. Many miRNAs that exhibit the greatest differences between males and females have established roles in neurodevelopment, implying that sex-biased expression may drive sex differences in developmental processes. In addition to highlighting sex differences for individual miRNAs, gene ontology analysis suggested several broad categories in which sex-biased RNAs might act to establish sex differences in the embryonic mouse brain. Finally, mining publicly available SNP data indicated that some sex-biased miRNAs reside near the genomic regions associated with neurodevelopmental disorders.

Conclusions

Together, these findings reinforce the importance of cataloguing sex differences in molecular biology research and highlight genes, miRNAs, and pathways of interest that may be important for sexual differentiation in the mouse and possibly the human brain.
How biofilm changes our understanding of cleaning and disinfection
Authors: Maillard Jean-Yves , Centeleghe Isabella
Published: September 2023

Biofilms are ubiquitous in healthcare settings. By nature, biofilms are less susceptible to antimicrobials and are associated with healthcare-associated infections (HAI). Resistance of biofilm to antimicrobials is multifactorial with the presence of a matrix composed of extracellular polymeric substances and eDNA, being a major contributing factor. The usual multispecies composition of environmental biofilms can also impact on antimicrobial efficacy. In healthcare settings, two main types of biofilms are present: hydrated biofilms, for example, in drains and parts of some medical devices and equipment, and environmental dry biofilms (DSB) on surfaces and possibly in medical devices. Biofilms act as a reservoir for pathogens including multi-drug resistant organisms and their elimination requires different approaches. The control of hydrated (drain) biofilms should be informed by a reduction or elimination of microbial bioburden together with measuring biofilm regrowth time. The control of DSB should be measured by a combination of a reduction or elimination in microbial bioburden on surfaces together with a decrease in bacterial transfer post-intervention. Failure to control biofilms increases the risk for HAI, but biofilms are not solely responsible for disinfection failure or shortcoming. The limited number of standardised biofilm efficacy tests is a hindrance for end users and manufacturers, whilst in Europe there are no approved standard protocols. Education of stakeholders about biofilms and ad hoc efficacy tests, often academic in nature, is thus paramount, to achieve a better control of biofilms in healthcare settings.
Positron emission tomography imaging of the sodium iodide symporter senses real-time energy stress in vivo
Authors: Dzien Piotr , Mackintosh Agata , Malviya Gaurav , Johnson Emma , Soloviev Dmitry , Brown Gavin , Uribe Alejandro Huerta , Nixon Colin , Lyons Scott K. , Maddocks Oliver , Blyth Karen , Lewis David Y.
Published: September 2023

Background

Tissue environment is critical in determining tumour metabolic vulnerability. However, in vivo drug testing is slow and waiting for tumour growth delay may not be the most appropriate endpoint for metabolic treatments. An in vivo method for measuring energy stress would rapidly determine tumour targeting in a physiologically relevant environment. The sodium-iodide symporter (NIS) is an imaging reporter gene whose protein product co-transports sodium and iodide, and positron emission tomography (PET) radiolabelled anions into the cell. Here, we show that PET imaging of NIS-mediated radiotracer uptake can rapidly visualise tumour energy stress within minutes following in vivo treatment.

Methods

We modified HEK293T human embryonic kidney cells, and A549 and H358 lung cancer cells to express transgenic NIS. Next, we subjected these cells and implanted tumours to drugs known to induce metabolic stress to observe the impact on NIS activity and energy charge. We used [18F]tetrafluoroborate positron emission tomography (PET) imaging to non-invasively image NIS activity in vivo.

Results

NIS activity was ablated by treating HEK293T cells in vitro, with the Na+/K+ ATPase inhibitor digoxin, confirming that radiotracer uptake was dependent on the sodium–potassium concentration gradient. NIS-mediated radiotracer uptake was significantly reduced (− 58.2%) following disruptions to ATP re-synthesis by combined glycolysis and oxidative phosphorylation inhibition in HEK293T cells and by oxidative phosphorylation inhibition (− 16.6%) in A549 cells in vitro. PET signal was significantly decreased (− 56.5%) within 90 min from the onset of treatment with IACS-010759, an oxidative phosphorylation inhibitor, in subcutaneous transgenic A549 tumours in vivo, showing that NIS could rapidly and sensitively detect energy stress non-invasively, before more widespread changes to phosphorylated AMP-activated protein kinase, phosphorylated pyruvate dehydrogenase, and GLUT1 were detectable.

Conclusions

NIS acts as a rapid metabolic sensor for drugs that lead to ATP depletion. PET imaging of NIS could facilitate in vivo testing of treatments targeting energetic pathways, determine drug potency, and expedite metabolic drug development.
Sea surface temperature clustering and prediction in the Pacific Ocean based on isometric feature mapping analysis
Authors: Tseng John Chien-Han , Tsai Bo-An , Chung Kaoshen
Published: September 2023

Isometric feature mapping (ISOMAP) is a nonlinear dimensionality reduction method and closely reflects the actual nonlinear distance by the view of tracing along the local linearity in the original nonlinear structure. Thus, the first leading 20 principal components (PCs) of low-dimensional space can reveal the characteristics of real structures and be utilized for clustering. In this study, a k-means algorithm was used to diagnose SST clustering based on ISOMAP. Warm and cold El Niño–Southern Oscillation events were subdivided into Central Pacific and Eastern Pacific types, and a two-dimensional cluster map was used to depict the relationship. The leading low-dimensional PCs of ISOMAP were considered as the orthogonal basis, and their trajectories demonstrated meaningful patterns that could be learned by machine learning algorithms. Predictions of SST in the Pacific Ocean were performed using support vector regression (SVR) and feedforward neural network (NN) models based on the low-dimensional PCs of ISOMAP. The forecast skills, the root-mean-square error (RMSE) and anomaly correlation coefficient (ACC), were comparable to those of current numerical models.
Delineation of shallow volcanic structures from audio-frequency magnetotelluric data beneath Ulleung Island, East Sea (Sea of Japan)
Authors: Hong Jinpyo , Kim Kiyeon , Oh Seokhoon , Kwon Hyoung-Seok , Choi Sung Hi , Park Sun-Cheon
Published: September 2023

As volcanoes are closely related to the living environment of humans, in particular via natural hazards and geothermal energy, scientific studies on volcanic edifice structures are required. Ulleung Island is a Quaternary volcanic island located in the mid-western East Sea (Sea of Japan). In this study, we conducted an audio-frequency magnetotelluric (AMT) survey to image the substructure of the Ulleung volcanic edifice. In addition, the electrical structure was interpreted from the geothermal system perspective, geochemical compositions of volcanic rocks, and the possibility of the presence of a magma reservoir. AMT data were obtained from 25 stations and processed using the remote reference technique. Then, the three-dimensional (3-D) approach was reasonably adopted according to dimensionality analysis. Before conducting the 3-D inversion, the effects on topography and ocean were analyzed using a simplified 3-D synthetic model, because Ulleung Island is surrounded by sea and the topography is undulating. Most AMT stations on Ulleung Island are distorted by topographical and oceanic effects; in particular, oceanic effects are significant at frequencies lower than 10 Hz. The 3-D inversion was conducted with full impedance components and vertical magnetic transfer functions in a frequency range of 10,000–1 Hz. The results show that the Ulleung volcanic edifice is characterized by two layers of electrical structures as follows: near-surface resistive anomalies and an underlying conductive layer. Considering the high geothermal gradient on Ulleung Island, we suggest that the conductive layer of the volcanic edifice is due to hydrothermal alteration of basaltic rocks, with a potential heat source underneath. Based on the geochemical characteristics of the Ulleung volcanic rocks, the possibility of heat transfer from a trachytic magma reservoir within the shallow crustal is suggested. In summary, this study presents a geological interpretation of shallow volcanic structures beneath Ulleung Island and the possibility of an active magma reservoir as a potential heat source for the volcanic edifice.

Graphical Abstract
Evolution of neurodegeneration in patients with normal pressure hydrocephalus: a monocentric follow up study
Authors: Klemke Leonard L. , Müller-Schmitz Katharina , Kolman Aschwin , Seitz Rüdiger J.
Published: September 2023

Background

The aim of this study was to examine in patients with idiopathic and neurodegenerative normal pressure hydrocephalus (NPH) if motor and cognitive performance as well as changes in biomarkers in cerebrospinal fluid (CSF) evolve differently.

Methods

41 patients with a typical clinical and MR-/CT-morphological presentation of NPH divided into an Alzheimer-negative (AD–, n = 25) and an Alzheimer-positive (AD+, n = 16) group according to neurodegenerative biomarkers (S100 protein, neuron-specific enolase, β-amyloid 1–42, Tau protein, phospho-Tau, protein-level and CSF pressure) in CSF. Follow-up of cognitive and gait functions before and after a spinal tap of 40–50 ml CSF of up to 49 months. Clinical, motor, neuropsychological and CSF biomarkers were analyzed using a repeated multifactorial analysis of variance (ANOVA) with post-hoc testing.

Results

Gait and neuropsychological performance and CSF biomarkers evolved differently between the AD− and AD+ patients. In particular, the AD+ patients benefited from the spinal tap regarding short-term memory. In contrast, gait parameters worsened over time in the AD+ patients, although they showed a relevant improvement after the first tap.

Conclusions

The results substantiate the recently reported association between a tap-responsive NPH and CSF changes of Alzheimer disease. Furthermore, they suggest that the AD changes in CSF manifest in an age-related fashion in AD− patients presenting with NPH.
The effect of preemptive gabapentin and pregabalin on postoperative pain of septoplasty with and without turbinoplasty: a randomized triple-blind controlled clinical trial
Authors: Abbasi Rohollah , Hashemian Farnaz , Ahmadi Mohammad Saeed , Jahanshahi Javaneh , Khoshraftar Ebrahim , Karimian Amin , Moradi Abbas
Published: September 2023

Background

Septoplasty is a painful process. Nowadays, opioids and non-opioids are used to control patients’ pain, which has different efficacy and consequences. We aimed to assess the effect of preemptive gabapentin and pregabalin on postoperative pain of septoplasty with and without turbinoplasty.

Methods

This randomized triple-blind controlled clinical trial was performed on patients over 18 years who were candidates for elective septoplasty in Besat Hospital of Hamadan. In this study, 102 patients were randomly assigned to three equal groups, including pregabalin, gabapentin, and placebo. The pain score (VAS scale), analgesic use, and complications were assessed at the second, sixth, and 16th hours after surgery.

Results

Results showed that the mean pain score in the control group was higher than pregabalin and gabapentin at all times after surgery (P < 0.001). However, there was no significant difference between the pregabalin and gabapentin groups (P = 0.729). At the second and sixth hours after surgery, the amount of analgesic used in the control group was significantly higher than pregabalin and gabapentin (P < 0.001). But there was no significant difference between pregabalin and gabapentin groups regarding the used analgesics. Also, at 6 h after surgery, the incidence of complications in the control group was significantly higher than in the pregabalin group (P = 0.006), but there was no statistically significant difference between the control group and the gabapentin group.

Conclusions

Administering gabapentin or pregabalin, 1 h before surgery in patients undergoing septoplasty with or without turbinoplasty, can reduce postoperative pain and complications. Therefore, it is recommended to administer 300 mg oral pregabalin or 600 mg oral gabapentin 1 h before surgery to reduce pain after septoplasty.

Trial registration

Iranian Registry of Clinical Trials, IRCT2015112024852N2. Registered on August 28, 2016—retrospectively registered,  https://www.irct.ir/trial/20897.
Generalized internal multiple prediction for low relief structures
Authors: Zhang Dongliang , Tsingas Constantinos , Almubarak Mohammed S. , Liang Hong
Published: September 2023

Correlation- and convolution-based internal multiple prediction is one of the most common methods to predict and subsequently attenuate internal multiples. This technique requires the convolution of two seismic events from the deep section followed by the correlation with an event from the shallow part section to satisfy the so-called deep-shallow-deep (late-early-late) condition; otherwise, nonphysical seismic events can be predicted. To comply with this condition, seismic data are separated into shallow and deep portions according to a given phantom horizon. Internal multiples whose raypaths pass through the phantom horizon four times are predicted for one trial. In this way, only a portion of internal multiples are predicted. To address this limitation, a novel algorithm called the generalized internal multiple prediction (GIMP) algorithm is proposed. This algorithm is founded upon the adaptation of the deep-shallow correlation and deep-deep convolution techniques, constrained by specific integration boundaries. The GIMP method effectively accommodates the deep-shallow-deep (late-early-late) mode, without necessitating the segmentation of the seismic data set into shallow and deep segments via a user-defined phantom horizon. Notably, this approach is comprehensive in nature and has the capability to predict all potential internal multiples concurrently. Considering the computational cost, the current implementation focus of GIMP is primarily on 1D or 1.5D; however, GIMP is applicable to 2D and 3D scenarios.
Improving Access to Cancer Clinical Trials for Patients From Culturally and Linguistically Diverse Backgrounds in Australia: A Survey of Clinical and Research Professionals
Authors: Pal Abhijit , Smith Ben , Allan Christie , Karikios Deme , Boyle Frances
Published: September 2023

Barriers and solutions to cancer clinical trial access in Australia—results from a national survey.
The physiological consequences of a very large natural meal in a voracious marine fish, the staghorn sculpin (Leptocottus armatus)
Authors: Wood Chris M. , Wang Jun , Jung Ellen H. , Pelster Bernd
Published: September 2023

Little information exists on physiological consequences when wild fish eat natural food. Staghorn sculpins at 10–13°C voluntarily consumed 15.8% of their body mass in anchovies. Gastric clearance was slow with >60% of the meal retained in the stomach at 48 h, and was not complete until 84 h. At 14–24 h post-feeding, pH was depressed by 3 units and Cl− concentration was elevated 2-fold in gastric chyme, reflecting HCl secretion, while in all sections of the intestine, pH declined by 1 pH unit but Cl− concentration remained unchanged. PCO2 and total ammonia concentration were greatly elevated throughout the tract, whereas PNH3 and HCO3− concentration were depressed. Intestinal HCO3− secretion rates, measured in gut sacs in vitro, were also lower in fed fish. Whole-animal O2 consumption rate was elevated approximately 2-fold for 72 h post-feeding, reflecting ‘specific dynamic action’, whereas ammonia and urea-N excretion rates were elevated about 5-fold. Arterial blood exhibited a modest ‘alkaline tide’ for about 48 h, but there was negligible excretion of metabolic base to the external seawater. PaCO2 and PaO2 remained unchanged. Plasma total amino acid concentration and total lipid concentration were elevated about 1.5-fold for at least 48 h, whereas small increases in plasma total ammonia concentration, PNH3 and urea-N concentration were quickly attenuated. Plasma glucose concentration remained unchanged. We conclude that despite the very large meal, slow processing with high efficiency minimizes internal physiological disturbances. This differs greatly from the picture provided by previous studies on aquacultured species using synthetic diets and/or force-feeding. Questions remain about the role of the gastro-intestinal microbiome in nitrogen and acid–base metabolism.
Κρατική συγκρότηση, συστημικές πιέσεις και συμμαχίες στη Μέση Ανατολή (1979- 1995)
Authors: Τασόπουλος Ηλίας
Published: September 2023

Η μελέτη των προσπαθειών και των δυνατοτήτων ενός κράτους να επηρεάζει και να διαμορφώνει το εξωτερικό περιβάλλον του έχει συμβάλλει στην οργάνωση μίας πολυεπίπεδης πραγματικότητας διεθνών σχέσεων. Σε αυτό το πλαίσιο, η διατριβή επιχειρεί να απαντήσει ορισμένα βασικά ερωτήματα των διεθνών σχέσεων μέσω της εξέτασης της εξωτερικής πολιτικής των αραβικών κρατών. Ποια είναι τα κίνητρα της συμπεριφοράς ενός κράτους στη σύναψη μίας διακρατικής συμμαχίας; Κατά πόσο συσχετίζονται η άσκηση εξωτερικής πολιτικής με την περίοδο συγκρότησης των βασικών δομών του κράτους; Πως μπορεί η μελέτη περιφερειών, όπως η Μέση Ανατολή, να συνεισφέρει ουσιαστικά στη θεωρητική συζήτηση περί της συμπεριφοράς των κρατών;Ο εικοστός αιώνας αποτελεί την περίοδο όπου το κράτος εδραιώνει την παρουσία του ως παράγοντας των διεθνών σχέσεων του αραβικού κόσμου, ενώ ισχυρές δυνάμεις εκτός της Μέσης Ανατολής αποκτούν σημαντική επιρροή στην περιοχή. Αυτή η διαμορφωτική περίοδος κορυφώνεται με την πρώτη και τη δεύτερη συμφωνία ειρήνης του Ισραήλ με αραβικά κράτη, το 1979 με την Αίγυπτο και το 1994 με την Ιορδανία αντίστοιχα. Μέσω της μελέτης των διεθνών σχέσεων του αραβικού κόσμου αποδεικνύεται πως οι βασικές επιλογές εξωτερικής πολιτικής των κρατών συνδέονται άμεσα με την περίοδο συγκρότησης των βασικών δομών τους και τη νομιμοποίηση των ρυθμίσεων του περιφερειακού συστήματος.
Efficacy of lung boost device on pulmonary function and chest expansion in pleural effusion patient: a randomized control trial protocol
Authors: Zunzunwala Saurabh , Vardhan Dr Vishnu
Published: September 2023

Background: The respiratory system is consisting of alveoli, bronchioles, pleura etc. The pleura is the name for the layer of tissue that is thin covers every lung and folds to the back side and creates border of the cavity of chest. Pleural effusion medically is termed for an accumulation of fluid above the required amount in the pleural space. Firstly, while evaluating the subjects with effusion of pleura is to determine if it is an exudate or a transudate. The factors that are pathophysiological may be clinically significant and play role in differentiating trait of effusion of pleura -transudate vs. exudates-include oncotic pressure that is low, increase in pressure of pulmonary capillary, increased permeability, obstruction of lymphatic system, and lowered pressure between pleura.

Aim: To find the efficacy of the lung boost device on pulmonary functions and chest expansion in pleural effusion patient.

Methods: A total of 70 of participants with pleural effusion would be taken in the study and they are separated in two groups 35 participants in single group. Group A would be having lung boost device and group B would be treated with Conventional Physiotherapy program which will be included in both the groups. Treatment will last for two weeks with six sessions a week. Pre- and post-intervention pulmonary function test and chest expansion would be found out and would be sent for the analysis.

Expected results: The results of the study are expected to prove lung boost device is more effective than conventional physiotherapy. So that it can help in increasing expansion of chest and function of pulmonary system of patients with effusion of pleura.
Randomized clinical trial evaluating the effect of metacognitive interventions on planning skills in children with attention-deficit/hyperactivity disorder (ADHD) with mixed symptom presentation. Pilot trial design
Authors: Kajka Natalia , Kulik Agnieszka
Published: September 2023

Cel pracy

Celem pilotażowego badania eksperymentalnego była ocena wpływu 25 interwencji metapoznawczych na umiejętność planowania u dzieci z ADHD.

Metoda

W eksperymencie uczestniczyło 45 dzieci z ADHD o typie mieszanym, w wieku 7-12 lat (M = 10,41; SD = 1,42), wraz z rodzicem. Dzieci zostały losowo przydzielone do jednej z trzech grup, określających rodzaj zastosowanej techniki metakognitywnej w treningu: grupa Mapa Myśli, grupa Notatka Rysunkowa, grupa kontrolna. Następnie brały udział w 25 tematycznych treningach.
Pomiar był wykonywany na początku i na końcu treningów za pomocą narzędzi: Kwestionariusz Conners 3, Test Mapy Parku.

Wyniki

Stwierdzono istotne różnice w nasileniu średnich wyników dla zmiennej planowanie między pierwszym a drugim pomiarem (M1 = 6,13; SD1 = 0,35; M2 = 5,67; SD2 = 0,82) w grupie kontrolnej oraz nieistotne różnice w natężeniu średnich wyników dla tej zmiennej w grupach Mapa Myśli i Notatka Rysunkowa. Wynik uzyskany w zakresie siły efektu dla wyniku istotnego jest wysoki (rc = 0,53).

Wnioski

U dzieci, które nie uczestniczyły w treningu, wynik uległ pogorszeniu, a w grupach eksperymentalnych wyniki były bez zmian.