bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of muscle mass-based indications for the cystatin C test in renal function evaluation
Authors: Yim Jisook , Son Nak-Hoon , Kim Kyoung Min , Yoon Dukyong , Cho Yonggeun , Kyong Taeyoung , Moon Ja-Young , Yi Tae Im , Lee Sang-Guk , Park Yongjung , Lee Jung Joo , Kim Kyung-Ah , Lee Jung Eun , Kim Jeong-Ho
Published: November 2022

Background

We aimed to suggest muscle mass-based criteria for using of the cystatin C test for the accurate estimated glomerular filtration rate (eGFR).

Materials and methods

We recruited 138 Korean subjects and evaluated eGFRcr (derived from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) based on creatinine) was compared to eGFRcys based on cystatin C as the reference value. The skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) was used as representative of muscle mass. Calf circumference (CC) was also evaluated. We defined the patients by eGFRcr as those with values of eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2 as the detection of hidden renal impairment (DHRI). Cut-off values were determined based on muscle mass for the cases of DHRI suggesting the criteria of cystatin C test in renal function evaluation.

Results

We confirmed significant negative correlation between %difference of eGFRcr from eGFRcys and SMI (r, −0.592 for male, −0.484 for female) or CC (r, −0.646 for male, −0.351 for female). SMI of 7.3 kg/m2 for males and 5.7 kg/m2 for females were suggested to be significant cutoffs for indication of cystatin C test. We also suggested CC would be valuable for cystatin C indication.

Conclusion

We suggested the muscle mass-based objective criteria relating to SMI and CC that would indicate the use of cystatin C to evaluate renal function test in sarcopenic cases. Our results highlight the importance of muscle mass-based selection of renal function.
Progressive fibrosing interstitial lung disease in rheumatoid arthritis: A retrospective study
Authors: Denis Anna , Henket Monique , Ernst Marie , Maes Nathalie , Thys Marie , Regnier Céline , Malaise Olivier , Frix Anne-Noëlle , Gester Fanny , Desir Colin , Meunier Paul , Louis Renaud , Malaise Michel , Guiot Julien
Published: November 2022

Background and objective

Rheumatoid arthritis associated-interstitial lung disease (RA-ILD) is the most common pulmonary manifestation of rheumatoid arthritis (RA) and an important cause of mortality. In patients suffering from interstitial lung diseases (ILD) from different etiologies (including RA-ILD), a significant proportion is exhibiting a fibrotic progression despite immunosuppressive therapies, defined as progressive fibrosing interstitial lung disease (PF-ILD). Here, we report the frequency of RA-ILD and PF-ILD in all RA patients’ cohort at University Hospital of Liège and compare their characteristics and outcomes.

Methods

Patients were retrospectively recruited from 2010 to 2020. PF-ILD was defined based on functional, clinical and/or iconographic progression criteria within 24 months despite specific anti-RA treatment.

Results

Out of 1,500 RA patients, about one third had high-resolution computed tomography (HRCT) performed, 89 showed RA-ILD and 48 PF-ILD. RA-ILD patients were significantly older than other RA patients (71 old of median age vs. 65, p < 0.0001), with a greater proportion of men (46.1 vs. 27.7%, p < 0.0001) and of smoking history. Non-specific interstitial pneumonia pattern was more frequent than usual interstitial pneumonia among RA-ILD (60.7 vs. 27.0%) and PF-ILD groups (60.4 vs. 31.2%). The risk of death was 2 times higher in RA-ILD patients [hazard ratio 2.03 (95% confidence interval 1.15–3.57), p < 0.01] compared to RA.

Conclusion

We identified a prevalence of PF-ILD of 3% in a general RA population. The PF-ILD cohort did not seem to be different in terms of demographic characteristics and mortality compared to RA-ILD patients who did not exhibit the progressive phenotype yet.
Complete resolution of stage II avascular necrosis affecting three joints by hyperbaric oxygen in a patient with sickle cell disease: A case report
Authors: Alshurafa Awni , Elhissi Mohammad , Yassin Mohamed A.
Published: November 2022

Avascular necrosis (AVN) or joint osteonecrosis is a debilitating complication of sickle cell disease, increasing the disease burden on both patients and healthcare systems. AVN can be radiologically categorized into early and late stages depending on the extent of the disease. Management of AVN is challenging and controversial. Generally, it includes conservative measures for early disease to preserve the joint for as long as possible and surgical management for more advanced diseases. Hyperbaric oxygen (HBO) therapy can be used as primary or adjunctive therapy for different medical disorders. Currently, the main rule of HBO in AVN is an adjunctive therapy to control symptoms and improve the quality of life of a patient; however, the concept of using HBO as a primary treatment choice for AVN in patients with sickle cell disease is not well evaluated yet. In this case study, we reported a 15-year-old boy with sickle cell disease who was suffering from stage II AVN in bilateral femoral and right shoulder joints. A total of 57 sessions of HBO resulted in the complete resolution of AVN in post-treatment MRI.
Retinal changes in patients with idiopathic inflammatory myopathies: A case-control study in the MyoCite cohort
Authors: Aggarwal Rachna , Naveen R. , Thakare Darpan , Shahi Rohit , Anuja Anamika Kumari , Husain Ahmad , Abbasi Maryam , Rathore Upendra , Agarwal Vikas , Gupta Latika
Published: November 2022

Background

Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with Idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health.

Methods

Adult and Juvenile IIM patients (2017 ACR/EULAR criteria), visiting a tertiary care center in 2021 were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis.

Results

43 patients with IIM [31 females; age 36 (23–45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6 vs. 4.3%,p< 0.001), AV nicking (14 vs. 2.2%,p= 0.053), and vascular tortuosity (18.6 vs. 2.2%, p= 0.012), besides decreased visual acuity (53.5 vs. 10.9%, p<0.001) and immature cataracts (34.9 vs. 2.2%,p< 0.001). Attenuation of vessels [OR 10.9 (1.7–71), p= 0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p= 0.068], especially attenuation of vessels [14(38%) vs. 0(0), p= 0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI.

Conclusion

Retinal microvasculopathy and diminution of vision occur in nearly one-thirds to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.
18F-FDG PET molecular imaging: A relevant tool to investigate chronic inflammatory rheumatisms in clinical practice?
Authors: Pean De Ponfilly – Sotier Marie , Seror Raphaële , Nocturne Gaetane , Besson Florent L.
Published: November 2022

18F-Labeled Fluorodeoxyglucose-Positron Emission Tomography (18F-FDG PET) is a molecular imaging tool commonly used in practice for the assessment of many cancers. Thanks to its properties, its use has been progressively extended to numerous inflammatory conditions, including chronic inflammatory rheumatism (CIR) such as rheumatoid arthritis (RA), spondylarthritis (SpAs) and polymyalgia rheumatica (PMR). 18F-FDG PET is currently not recommended for the diagnostic of CIRs. However, this whole-body imaging tool has emerged in clinical practice, providing a general overview of systemic involvement occurring in CIRs. Numerous studies have highlighted the capacity of 18F-FDG PET to detect articular and extra articular involvements in RA and PMR. However, the lack of specificity of 18F-FDG limits its use for diagnosis purpose. Finally, the key question is the definition of the best way to integrate this whole-body imaging tool in the patient’s management workflow.
Short interpregnancy interval can lead to adverse pregnancy outcomes: A meta-analysis
Authors: Wang Yumei , Zeng Can , Chen Yuhong , Yang Liu , Tian Di , Liu Xinghui , Lin Yonghong
Published: November 2022

Background

The evidence of some previous papers was insufficient in studying the causal association between interpregnancy interval (IPI) and adverse pregnancy outcomes. In addition, more literature have been updated worldwide during the last 10 years.

Methods

English and Chinese articles published from January 1980 to August 2021 in the databases of PubMed, Cochrane Library, Ovid, Embase, China Biology Medicine disc (CBM), and China National Knowledge Infrastructure (CNKI) were searched. Then following the inclusion and exclusion criteria, we screened the articles. Utilizing the Newcastle–Ottawa Scale (NOS), we evaluated the quality of the included articles. The literature information extraction table was set up in Excel, and the meta-analysis was performed with Stata 16.0 software (Texas, USA).

Results

A total of 41 articles were included in the meta-analysis, and NOS scores were four to eight. The short IPI after delivery was the risk factor of preterm birth (pooled odds ratio 1.49, 95% confidence interval 1.42–1.57), very preterm birth (pooled OR: 1.82, 95% CI: 1.55–2.14), low birth weight (pooled OR: 1.33, 95% CI: 1.24–1.43), and small for gestational age (pooled OR: 1.14, 95% CI: 1.07–1.21), offspring death (pooled OR: 1.60, 95% CI: 1.51–1.69), NICU (pooled OR: 1.26, 95% CI: 1.01–1.57), and congenital abnormality (pooled OR: 1.10, 95% CI: 1.05–1.16), while was not the risk factor of gestational hypertension (pooled OR: 0.95, 95% CI: 0.93–0.98) or gestational diabetes (pooled OR: 1.06, 95% CI: 0.93–1.20).

Conclusion

Short IPI (IPI < 6 months) can lead to adverse perinatal outcomes, while it is not a risk factor for gestational diabetes and gestational hypertension. Therefore, more high-quality studies covering more comprehensive indicators of maternal and perinatal pregnancy outcomes are needed to ameliorate the pregnancy policy for women of childbearing age.
River damming enhances ecological functional stability of planktonic microorganisms
Authors: Li Wanzhu , Wang Baoli , Liu Na , Yang Meiling , Liu Cong-Qiang , Xu Sheng
Published: November 2022

Planktonic microorganisms play an important role in maintaining the ecological functions in aquatic ecosystems, but how their structure and function interrelate and respond to environmental changes is still not very clear. Damming interrupts the river continuum and alters river nutrient biogeochemical cycling and biological succession. Considering that river damming decreases the irregular hydrological fluctuation, we hypothesized that it can enhance the ecological functional stability (EFS) of planktonic microorganisms. Therefore, the community composition of planktonic bacteria and archaea, functional genes related to carbon, nitrogen, sulfur, and phosphorus cycling, and relevant environmental factors of four cascade reservoirs in the Pearl River, Southern China, were investigated to understand the impact of damming on microbial community structure and function and verify the above hypothesis. Here, the ratio of function to taxa (F:T) based on Euclidean distance matrix analysis was first proposed to characterize the microbial EFS; the smaller the ratio, the more stable the ecological functions. The results showed that the reservoirs created by river damming had seasonal thermal and chemical stratifications with an increasing hydraulic retention time, which significantly changed the microbial structure and function. The river microbial F:T was significantly higher than that of the reservoirs, indicating that river damming enhances the EFS of the planktonic microorganisms. Structural equation modeling demonstrated that water temperature was an important factor influencing the relationship between the microbial structure and function and thus affected their EFS. In addition, reservoir hydraulic load was found a main factor regulating the seasonal difference in microbial EFS among the reservoirs. This study will help to deepen the understanding of the relationship between microbial structure and function and provide a theoretical basis of assessing the ecological function change after the construction of river damming.
A putative multi-sensor hybrid histidine kinase, BarAAc, inhibits the expression of the type III secretion system regulator HrpG in Acidovorax citrulli
Authors: Qiao Pei , Zhao Mei , Guan Wei , Walcott Ron , Ye Yunfeng , Yang Yuwen , Zhao Tingchang
Published: November 2022

Bacterial fruit blotch (BFB), caused by Acidovorax citrulli, severely damages watermelon, melon, and other cucurbit crops worldwide. Although many virulence determinants have been identified in A. citrulli, including swimming motility, twitching motility, biofilm formation, and the type III secretion system (T3SS), research on their regulation is lacking. To study virulence regulation mechanisms, we found a putative histidine kinase BarAAc that may be related to the T3SS regulator HrpG in A. citrulli. We deleted and characterized barAAc (Aave_2063) in A. citrulli Aac5 strain. Compared to the wild-type Aac5, virulence and early proliferation of barAAc mutant in host watermelon cotyledons were significantly increased, and induction of hypersensitive response in non-host tobacco was accelerated, while biofilm formation and swimming motility were significantly reduced. In addition, the transcriptomic analysis revealed that the expression of many T3SS-related genes was upregulated in the ΔbarAAc deletion mutant when cultured in KB medium. Meanwhile, the ΔbarAAc deletion mutant showed increased accumulation of the T3SS regulator HrpG in KB medium, which may account for the increased deployment of T3SS. This suggests that the putative histidine kinase BarAAc is able to repress the T3SS expression by inhibiting HrpG in the KB medium, which appears to be important for rational energy allocation. In summary, our research provides further understanding of the regulatory network of A. citrulli virulence.
A Chinese herbs complex ameliorates gut microbiota dysbiosis induced by intermittent cold exposure in female rats
Authors: Jin Lu , Bian Xiangyu , Dong Weiyun , Yang Renren , Jing Che , Li Xi , Yang Danfeng , Guo Changjiang , Gao Weina
Published: November 2022

Cold is a common source of stress in the alpine areas of northern China. It affects the microbial community, resulting in the invasion of pathogenic microorganisms and intestinal diseases. In recent years, studies have reported that Chinese herbal extracts and their fermentation broth have a significant beneficial effect on gut microbiota. This study aimed to investigate the probiotic effect of a self-designed Chinese herbs complex on the gut microbiota of rats exposed to cold. The rats were treated with intermittent cold exposure and Chinese herbs complex for 14 days, and the gut microbiota composition and other parameters were assayed. The 16s ribosomal DNA high-throughput sequencing and analysis confirmed that the Chinese herbs complex positively improved the gut microbiota. We found that cold exposure could lead to significant changes in the composition of gut microbiota, and affect the intestinal barrier and other physiological functions. The relative abundance of some probiotics in the genus such asRoseburia, Parasutterella, and Elusimicrobiumin rats treated with Chinese herbs complex was significantly increased. Serum D-lactic acid (D-LA) and lipopolysaccharide (LPS) were increased in the cold exposure group and decreased in the Chinese herbs complex-treated group. Moreover, the Chinese herbs complex significantly increased the protein expression of occludin. In conclusion, the Chinese herbs complex is effective in restoring the gut microbiota caused by cold exposure, improving the function of the intestinal barrier, and may act as a prebiotic in combatting gut dysbiosis.
The role of ADAM10 in astrocytes: Implications for Alzheimer’s disease
Authors: Elsworthy Richard J. , Hill Eric J. , Dunleavy Connor , Aldred Sarah
Published: November 2022

Much of the early research into AD relies on a neuron-centric view of the brain, however, evidence of multiple altered cellular interactions between glial cells and the vasculature early in AD has been demonstrated. As such, alterations in astrocyte function are widely recognized a contributing factor in the pathogenesis of AD. The processes by which astrocytes may be involved in AD make them an interesting target for therapeutic intervention, but in order for this to be most effective, there is a need for the specific mechanisms involving astrocyte dysfunction to be investigated. “α disintegrin and metalloproteinase” 10 (ADAM10) is capable of proteolytic cleavage of the amyloid precursor protein which prevents amyloid-β generation. As such ADAM10 has been identified as an interesting enzyme in AD pathology. ADAM10 is also known to play a role in a significant number of cellular processes, most notable in notch signaling and in inflammatory processes. There is a growing research base for the involvement of ADAM10 in regulating astrocytic function, primarily from an immune perspective. This review aims to bring together available evidence for ADAM10 activity in astrocytes, and how this relates to AD pathology.
Recent technological advances in correlative light and electron microscopy for the comprehensive analysis of neural circuits
Authors: Iwasaki Hirohide , Ichinose Sotaro , Tajika Yuki , Murakami Tohru
Published: November 2022

Light microscopy (LM) covers a relatively wide area and is suitable for observing the entire neuronal network. However, resolution of LM is insufficient to identify synapses and determine whether neighboring neurons are connected via synapses. In contrast, the resolution of electron microscopy (EM) is sufficiently high to detect synapses and is useful for identifying neuronal connectivity; however, serial images cannot easily show the entire morphology of neurons, as EM covers a relatively narrow region. Thus, covering a large area requires a large dataset. Furthermore, the three-dimensional (3D) reconstruction of neurons by EM requires considerable time and effort, and the segmentation of neurons is laborious. Correlative light and electron microscopy (CLEM) is an approach for correlating images obtained via LM and EM. Because LM and EM are complementary in terms of compensating for their shortcomings, CLEM is a powerful technique for the comprehensive analysis of neural circuits. This review provides an overview of recent advances in CLEM tools and methods, particularly the fluorescent probes available for CLEM and near-infrared branding technique to match LM and EM images. We also discuss the challenges and limitations associated with contemporary CLEM technologies.
Who's driving? The default mode network in healthy elderly individuals at risk of cognitive decline
Authors: González-López Mauricio , Gonzalez-Moreira Eduardo , Areces-González Ariosky , Paz-Linares Deirel , Fernández Thalía
Published: November 2022

Introduction

Age is the main risk factor for the development of neurocognitive disorders, with Alzheimer's disease being the most common. Its physiopathological features may develop decades before the onset of clinical symptoms. Quantitative electroencephalography (qEEG) is a promising and cost-effective tool for the prediction of cognitive decline in healthy older individuals that exhibit an excess of theta activity. The aim of the present study was to evaluate the feasibility of brain connectivity variable resolution electromagnetic tomography (BC-VARETA), a novel source localization algorithm, as a potential tool to assess brain connectivity with 19-channel recordings, which are common in clinical practice.

Methods

We explored differences in terms of functional connectivity among the nodes of the default mode network between two groups of healthy older participants, one of which exhibited an EEG marker of risk for cognitive decline.

Results

The risk group exhibited increased levels of delta, theta, and beta functional connectivity among nodes of the default mode network, as well as reversed directionality patterns of connectivity among nodes in every frequency band when compared to the control group.

Discussion

We propose that an ongoing pathological process may be underway in healthy elderly individuals with excess theta activity in their EEGs, which is further evidenced by changes in their connectivity patterns. BC-VARETA implemented on 19-channels EEG recordings appears to be a promising tool to detect dysfunctions at the connectivity level in clinical settings.
Efficacy and safety of hypoglycemic drugs in improving cognitive function in patients with Alzheimer's disease and mild cognitive impairment: A systematic review and network meta-analysis
Authors: Wang Xin-Chen , Chu Chen-Liang , Li Han-Cheng , Lu Kuan , Liu Cheng-Jiang , Cai Ye-Feng , Quan Shi-Jian , Zhang Shi-Jie
Published: November 2022

Objective

The purpose of this study was to compare the effects of oral hypoglycaemic drugs (HDs) on cognitive function and biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) through a network meta-analysis of randomized controlled trials (RCTs).

Methods

We conducted systematic searches for English- and Chinese-language articles in the PubMed, Medline, Embase, Cochrane Library and Google Scholar databases, with no date restrictions. We performed a network meta-analysis, which we report here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The 16 studies included a total of 3,081 patients. We selected the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living section (ADCS-ADL) and amyloid beta (Aβ) 42 as the outcome measures for analysis and comparison.

Result

We selected seven treatments and assessed the clinical trials in which they were tested against a placebo control. Of these treatments, intranasal insulin 20 IU (ITSN20), glucagon-like peptide-1 (GLP-1), and dipeptidyl peptidase 4 inhibitor (DPP-4) were associated with significantly improved MMSE scores (7 RCTs, 333 patients, 30≥MMSE score≥20: mild) compared with placebo [standardized mean difference (SMD) 1.11, 95% confidence interval (CI) (0.87, 1.35); SMD 0.75, 95% CI (0.04, 1.41); and SMD 4.08, 95% CI (3.39, 4.77), respectively]. Rosiglitazone 4 mg (RLZ4), rosiglitazone 10 mg (RLZ10), intranasal insulin 40 IU (ITSN40), and ITSN20 significantly decreased ADAS-Cog scores (11 RCTs, 4044 patients, 10 ≤ ADAS-Cog scores ≤ 30: mild and moderate) compared with placebo [SMD −1.40, 95% CI (−2.57, −0.23), SMD −3.02, 95% CI (−4.17, −1.86), SMD −0.92, 95% CI (−1.77, −0.08), SMD −1.88, 95% CI (−3.09, −0.66)]. Additionally, ITSN20 and ITSN40 significantly improved ADCS-ADL scores (2 RCTs, 208 patients, ADCS-ADL scale score ≤ 10: mild) compared with placebo [SMD 0.02, 95% CI (0.01, 0.03), and SMD 0.04, 95% CI (0.03, 0.05), respectively]. In the 16 included studies, the degree of AD was classified as mild or moderate. For mild cognitive impairment, DPP-4 performed best, but for mild to moderate impairment, ITSN40 had excellent performance.

Conclusion

Various HDs can improve the cognitive function of MCI and AD patients. Different drug regimens brought different degrees of improvement, which may be related to their dosage, duration, and mechanism of action.

Systematic review registration

www.crd.york.ac.uk/prospero.
Data and sample sharing as an enabler for large-scale biomarker research and development: The EPND perspective
Authors: Bose Niranjan , Brookes Anthony J. , Scordis Phil , Visser Pieter Jelle
Published: November 2022

Biomarker discovery, development, and validation are reliant on large-scale analyses of high-quality samples and data. Currently, significant quantities of data and samples have been generated by European studies on Alzheimer's disease (AD) and other neurodegenerative diseases (NDD), representing a valuable resource for developing biomarkers to support early detection of disease, treatment monitoring, and patient stratification. However, discovery of, access to, and sharing of data and samples from AD and NDD research are hindered both by silos that limit collaboration, and by the array of complex requirements for secure, legal, and ethical sharing. In this Perspective article, we examine key challenges currently hampering large-scale biomarker research, and outline how the European Platform for Neurodegenerative Diseases (EPND) plans to address them. The first such challenge is a fragmented landscape filled with technical barriers that make it difficult to discover and access high-quality samples and data in one location. A second challenge is related to the complex array of legal and ethical requirements that must be navigated by researchers when sharing data and samples, to ensure compliance with data protection regulations and research ethics. Another challenge is the lack of broad-scale collaboration and opportunities to facilitate partnerships between data and sample contributors and researchers, in addition to a lack of regulatory engagement early in the research process to enable validation of potential biomarkers. A further challenge facing projects is the need to remain sustainable beyond initial funding periods, ensuring data and samples are shared and reused, thereby driving further research and innovation. In addressing these challenges, EPND will enable an environment of faster and more disruptive research on diagnostics and disease-modifying therapies for Alzheimer's disease and other neurodegenerative diseases.
Intestinal proline is a potential anti-allergy factor for allergy diagnosis and therapy
Authors: Ma Jinya , Wang Chong , Wang Fangting , Zhang Yong , Liu Yinghua , Zhang Jiachao , Gao Zhongshan , Zhang Yi , Xie Hujun , Wang Yanbo , Fu Linglin
Published: November 2022

Allergy has become a public health problem worldwide, but effective diagnostic and therapeutic approaches are limited currently. Amino acids are essential macronutrients that potentially participated in the allergy process. This work aimed to investigate whether amino acids can be applied as a mediator for allergy diagnosis and therapy. Two cohort studies were performed to investigate the correlation between fecal amino acids and allergy responses, and a spleen cell model was used to validate the role of amino acids in regulating allergy. In a cohort study with 193 volunteers, fecal proline was found to be negatively correlated with serum IgE, and detailed data analysis revealed that people with high-IgE-mediated allergy had decreased odds of high intestinal proline. In another cohort study with distinct allergic and non-allergic individuals, proline concentration was significantly lower in the allergic group. Daily diet and metagenomics analysis showed that the proline intake and microbiota amino acid metabolism were not significantly different, implying that the body’s proline metabolism might be different between allergic and non-allergic individuals. Furthermore, the spleen cell model demonstrated that proline specifically targeted Th2 and Treg activity. Overall, this work revealed a tight correlation between gut proline and serum IgE, indicating proline as a promising biomarker and a potential therapeutic method for allergic diseases.
Fortification and bioaccessibility of saffron apocarotenoids in potato tubers
Authors: Gómez Gómez Lourdes , Morote Lucía , Frusciante Sarah , Rambla José Luis , Diretto Gianfranco , Niza Enrique , López-Jimenez Alberto José , Mondejar María , Rubio-Moraga Ángela , Argandoña Javier , Presa Silvia , Martín-Belmonte Alejandro , Luján Rafael , Granell Antonio , Ahrazem Oussama
Published: November 2022

Carotenoids are C40 isoprenoids with well-established roles in photosynthesis, pollination, photoprotection, and hormone biosynthesis. The enzymatic or ROS-induced cleavage of carotenoids generates a group of compounds named apocarotenoids, with an increasing interest by virtue of their metabolic, physiological, and ecological activities. Both classes are used industrially in a variety of fields as colorants, supplements, and bio-actives. Crocins and picrocrocin, two saffron apocarotenoids, are examples of high-value pigments utilized in the food, feed, and pharmaceutical industries. In this study, a unique construct was achieved, namely O6, which contains CsCCD2L, UGT74AD1, and UGT709G1 genes responsible for the biosynthesis of saffron apocarotenoids driven by a patatin promoter for the generation of potato tubers producing crocins and picrocrocin. Different tuber potatoes accumulated crocins and picrocrocin ranging from 19.41–360 to 105–800 μg/g DW, respectively, with crocetin, crocin 1 [(crocetin-(β-D-glucosyl)-ester)] and crocin 2 [(crocetin)-(β-D-glucosyl)-(β-D-glucosyl)-ester)] being the main compounds detected. The pattern of carotenoids and apocarotenoids were distinct between wild type and transgenic tubers and were related to changes in the expression of the pathway genes, especially from PSY2, CCD1, and CCD4. In addition, the engineered tubers showed higher antioxidant capacity, up to almost 4-fold more than the wild type, which is a promising sign for the potential health advantages of these lines. In order to better investigate these aspects, different cooking methods were applied, and each process displayed a significant impact on the retention of apocarotenoids. More in detail, the in vitro bioaccessibility of these metabolites was found to be higher in boiled potatoes (97.23%) compared to raw, baked, and fried ones (80.97, 78.96, and 76.18%, respectively). Overall, this work shows that potatoes can be engineered to accumulate saffron apocarotenoids that, when consumed, can potentially offer better health benefits. Moreover, the high bioaccessibility of these compounds revealed that potato is an excellent way to deliver crocins and picrocrocin, while also helping to improve its nutritional value.
Intake of slow-digesting carbohydrates is related to changes in the microbiome and its functional pathways in growing rats with obesity induced by diet
Authors: Plaza-Díaz Julio , Manzano Manuel , Ruiz-Ojeda Francisco Javier , Giron Maria D. , Salto Rafael , López-Pedrosa Jose M. , Santos-Fandila Angela , Garcia-Corcoles Maria Teresa , Rueda Ricardo , Gil Ángel
Published: November 2022

Introduction

The main cause of insulin resistance in childhood is obesity, which contributes to future comorbidities as in adults. Although high-calorie diets and lack of exercise contribute to metabolic disease development, food quality rather than the quantity of macronutrients is more important than food density. The purpose of the present study was to examine the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on the composition of the gut microbiota and the profiles of the functional pathways in growing rats with obesity due to a high-fat diet (HFD).

Methods

During the course of 4 weeks, rats growing on an HFD-containing carbohydrates with different digestive rates were fed either HFD-containing carbohydrates with a rapid digestion rate (OBE group) or HFD-containing carbohydrates with a slow digestion rate (OBE-ISR group). A non-obese group (NOB) was included as a reference, and rats were fed on a rodent standard diet (AIN93G). An analysis of gut microbiota was conducted using 16S rRNA-based metagenomics; a linear mixed-effects model (LMM) was used to determine changes in abundance between baseline and 4 weeks of treatment, and functional pathways were identified. Gut microbiota composition at bacterial diversity and relative abundance, at phylum and genus levels, and functional profiles were analyzed by integrating the Integrated Microbial Genomes (IMG) database.

Results

The groups showed comparable gut microbiota at baseline. At the end of the treatment, animals from the ISR group exhibited differences at the phylum levels by decreasing the diversity of Fisher’s index and Firmicutes (newly named as Bacillota), and increasing the Pielou’s evenness and Bacteroidetes (newly named as Bacteroidota); at the genus level by increasing Alistipes, Bifidobacterium, Bacteroides, Butyricimonas, Lachnoclostridium, Flavonifractor, Ruminiclostridium 5, and Faecalibaculum and decreasing Muribaculum, Blautia, and Ruminiclostridium 9. Remarkably, relative abundances of genera Tyzzerella and Angelakisella were higher in the OBE group compared to NOB and OBE-ISR groups. In addition, some microbiota carbohydrate metabolism pathways such as glycolysis, glucuronic acid degradation, pentose phosphate pathway, methanogenesis, and fatty acid biosynthesis exhibited increased activity in the OBE-ISR group after the treatment. Higher levels of acetate and propionate were found in the feces of the ISR group compared with the NOB and OBE groups.

Conclusion

The results of this study demonstrate that replacing rapidly digestible carbohydrates with slowly digestible carbohydrates within an HFD improve the composition of the gut microbiota. Consequently, metabolic disturbances associated with obesity may be prevented.
PD-L1 is associated with the prognosis of penile cancer: A systematic review and meta-analysis
Authors: Lu Yi , Wang Yutao , Su Hao , Li Hongjun
Published: November 2022

Background

Previous studies have explored the role of PD-L1 in the survival outcomes of penile cancer patients with controversies existed. Thus, the meta-analysis was conducted to report and review the association between PD-L1 and survival in penile cancer patients.

Methods

PubMed, Cochrane Library, EMBASE, and Web of Science were all searched, screened, and reviewed by June 1, 2022. Hazard ratio (HR) was used to evaluate the relationship between PD-L1 and survival outcome, and odds ratio (OR) was for tumor features.

Results

Nine retrospective studies (1,003 patients) were incorporated. The prevalence of PD-L1 in patients with penile cancer was 51.4% (95% CI = 42.1%-60.8%, I2 = 88.5%). Higher PD-L1 on tumor cells was related to shorter cancer-specific survival (CSS) in patients (HR = 1.578, 95% CI = 1.227-2.029, I2 = 23.3%), but had no associations with overall survival (OS) (HR = 1.123, 95% CI = 0.511-2.465, I2 = 0.0%). Subgroup analysis indicated that higher PD-L1 was related to shorter CSS in Caucasus (HR = 1.827, 95% CI = 1.355-2.465, I2 = 0.0%) only. Furthermore, PD-L1 had associations with tumor stage (pT1 vs. pT2-4, OR = 0.480, 95% CI = 0.346-0.667, P = 0.001) and tumor grade (Well and moderate vs. Poor, OR = 0.377, 95% CI = 0.264-0.538, P < 0.001). PD-L1 positivity was also related to lymph node (LN) status (pN0/NX vs. pN1–3, OR = 0.541, 95% CI = 0.385-0.759, P = 0.001) and HPV status (Positive vs. Negative, OR = 0.510, 95% CI = 0.322-0.810, P = 0.003). A trend toward statistical significance between PD-L1 and histological types was also observed (Usual SCC vs. Others, OR = 1.754, 95% CI = 0.984-3.124, P = 0.070).

Conclusions

PD-L1 over-expression was related to worse survival outcomes and several clinicopathological features of penile cancer. PD-L1 expression can be applied to select appropriate treatment strategies for penile malignancies.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=343041, identifier CRD42022343041.
Role of estrogen receptor signaling pathway-related genes in diffuse large B-cell lymphoma and identification of key targets via integrated bioinformatics analysis and experimental validation
Authors: Chen Bo , Mao Tianjiao , Qin Xiuni , Zhang Wenqi , Watanabe Nobumoto , Li Jiang
Published: November 2022

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy. Epidemiologically, the incidence of DLBCL is higher in men, and the female sex is a favorable prognostic factor, which can be explained by estrogen. This study aimed to explore the potential targets of the estrogen receptor (ER) signaling pathway and provide a meaningful way to treat DLBCL patients. Datasets were obtained from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). Representative gene sets estrogen receptor pathways, and growth regulatory pathways were identified based on Gene Set Enrichment Analysis (GSEA) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for function and pathway analysis. STRING and Cytoscape were used to construct the interaction network, and the MCODE plug-in performed the module analysis. GEPIA, TCGA, and LOGpc databases were used for expression and predictive analysis. The Human Protein Atlas (HPA) database was used to analyze the protein expression levels, cBioPortal was used to explore genetic alterations, and ROC analysis and prognostic assessment were used to predict the diagnostic value of genes. Finally, BJAB cells were treated with ER inhibitor fulvestrant and specific shRNA, and the expression of hub genes was verified by RT-qPCR. We identified 81 overlapping DEGs and CDC6, CDC20, KIF20A, STIL, and TOP2A as novel biomarkers affecting the prognosis of DLBCL. In addition, the STAT and KRAS pathways are considered potential growth regulatory pathways. These results hold promise for new avenues for the treatment of DLBCL patients.
Deep learning model for diagnosing early gastric cancer using preoperative computed tomography images
Authors: Zeng Qingwen , Feng Zongfeng , Zhu Yanyan , Zhang Yang , Shu Xufeng , Wu Ahao , Luo Lianghua , Cao Yi , Xiong Jianbo , Li Hong , Zhou Fuqing , Jie Zhigang , Tu Yi , Li Zhengrong
Published: November 2022

Background

Early gastric cancer (EGC) is defined as a lesion restricted to the mucosa or submucosa, independent of size or evidence of regional lymph node metastases. Although computed tomography (CT) is the main technique for determining the stage of gastric cancer (GC), the accuracy of CT for determining tumor invasion of EGC was still unsatisfactory by radiologists. In this research, we attempted to construct an AI model to discriminate EGC in portal venous phase CT images.

Methods

We retrospectively collected 658 GC patients from the first affiliated hospital of Nanchang university, and divided them into training and internal validation cohorts with a ratio of 8:2. As the external validation cohort, 93 GC patients were recruited from the second affiliated hospital of Soochow university. We developed several prediction models based on various convolutional neural networks, and compared their predictive performance.

Results

The deep learning model based on the ResNet101 neural network represented sufficient discrimination of EGC. In two validation cohorts, the areas under the curves (AUCs) for the receiver operating characteristic (ROC) curves were 0.993 (95% CI: 0.984-1.000) and 0.968 (95% CI: 0.935-1.000), respectively, and the accuracy was 0.946 and 0.914. Additionally, the deep learning model can also differentiate between mucosa and submucosa tumors of EGC.

Conclusions

These results suggested that deep learning classifiers have the potential to be used as a screening tool for EGC, which is crucial in the individualized treatment of EGC patients.
A systematic review and meta-analysis comparing tumor progression and complications between radiofrequency ablation and thyroidectomy for papillary thyroid carcinoma
Authors: Sun Yuan-dong , Zhang Hao , Zhu Hai-tao , Wu Chun-xue , Chen Miao-ling , Han Jian-jun
Published: November 2022

Background

Papillary thyroid cancer (PTC) is the most frequent thyroid cancers worldwide. The efficacy and acceptability of radiofrequency ablation (RFA) in the treatment of PTC have been intensively studied. The aim of this study is to focus on extra detailed that may influent for PTC or papillary thyroid microcarcinoma (PTMC).

Materials and methods

We identified a total of 1,987 records of a primary literature searched in PubMed, Embase, Cochrane Library, and Google Scholar by key words, from 2000 to 2022. The outcome of studies included complication, costs, and local tumor progression. After scrutiny screening and full-text assessment, six studies were included in the systematic review. Heterogeneity was estimated using I2, and the quality of evidence was assessed for each outcome using the GRADE guidelines.

Results

Our review enrolled 1,708 patients reported in six articles in the final analysis. There were 397 men and 1,311 women in the analysis. Two of these studies involved PTC and four focused on PTMC. There were 859 patients in the RFA group and 849 patients in the thyroidectomy group. By contrast, the tumor progression of RFA group was as same as that surgical groups [odds ratio, 1.31; 95% CI, 0.52–3.29; heterogeneity (I2 statistic), 0%, p = 0.85]. The risk of complication rates was significantly lower in the RFA group than that in the surgical group [odds ratio, 0.18; 95% CI, 0.09–0.35; heterogeneity (I2 statistic), 40%, p = 0.14].

Conclusions

RFA is a safe procedure with a certain outcome for PTC. RFA can achieve a good efficacy and has a lower risk of major complications.
Effect of spinal anesthesia-induced deafferentation on pain processing in healthy male volunteers: A task-related fMRI study
Authors: Sitsen Elske , Khalili-Mahani Najmeh , de Rover Mischa , Dahan Albert , Niesters Marieke
Published: November 2022

Background

Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the effect of spinal anesthesia on pain response to noxious thermal stimuli in non-deafferented skin areas using a functional magnetic resonance imaging (fMRI) paradigm.

Methods

Twenty-two healthy subjects participated in the study. We performed a task-based fMRI study using a randomized crossover design. Subjects were scanned under two conditions (spinal anesthesia or control) at two-time points: before and after spinal anesthesia. Spinal anesthesia resulted in sensory loss up to dermatome Th6. Calibrated heat-pain stimuli were administered to the right forearm (C8-Th1) using a box-car design (blocks of 10s on/25s off) during MRI scanning. Pain perception was measured using a visual analogue scale (1–100) at the beginning and the end of each session. Generalized estimating equations were used to examine the effect of intervention by time by order on pain scores. Similarly, higher-level effects were tested with appropriate general linear models (accounting for within-subject variations in session and time) to examine: (1) Differences in BOLD response to pain stimulus under spinal anesthesia versus control; and (2) Effects of spinal anesthesia on pain-related modulation of the cerebral activation.

Results

Complete fMRI data was available for eighteen participants. Spinal anesthesia was associated with moderate pain score increase. Significant differences in brain response to noxious thermal stimuli were present in comparison of spinal versus control condition (post—pre). Spinal condition was associated with higher BOLD signal in the bilateral inferior parietal lobule and lower BOLD signal in bilateral postcentral and precentral gyrus. Within the angular regions, we observed a positive correlation between pain scores and BOLD signal. These observations were independent from order effect (whether the spinal anesthesia was administered in the first or the second visit). However, we did observe order effect on brain regions including medial prefrontal regions, possibly related to anticipation of the experience of spinal anesthesia.

Conclusions

The loss of sensory and motor activity caused by spinal anesthesia has a significant impact on brain regions involved in the sensorimotor and cognitive processing of noxious heat pain stimuli. Our results indicate that the anticipation or experience of a strong somatosensory response to the spinal intervention might confound and contribute to increased sensitivity to cognitive pain processing. Future studies must account for individual differences in subjective experience of pain sensation within the experimental context.
Irigenin inhibits glioblastoma progression through suppressing YAP/β-catenin signaling
Authors: Xu Jiayun , Sun Shanshan , Zhang Wei , Dong Jianhong , Huang Changgang , Wang Xin , Jia Mengxian , Yang Hao , Wang Yongjie , Jiang Yuanyuan , Cao Liying , Huang Zhihui
Published: November 2022

Glioblastoma (GBM) is the most malignant glioma in brain tumors with low survival and high recurrence rate. Irigenin, as an isoflavone compound extracted from Shegan, has shown many pharmacological functions such as antioxidant, anti-inflammatory and anti-tumor. However, the effects of irigenin on GBM cells and the related molecular mechanisms remain unexplored. In this study, we found that irigenin inhibited the proliferation of GBM cells in a dose-dependent manner by several assays in vitro. Subsequently, we found that irigenin arrested cell cycle at G2/M phase and induced apoptosis of GBM cells in vitro. In addition, irigenin inhibited the migration of GBM cells. Mechanically, we found that irigenin treatment decreased the expression of YAP (yes-associated protein), suppressed β-catenin signaling. Furthermore, overexpression of YAP partially restored the anti-tumor effects of irigenin on GBM cells in vitro. Finally, we found that irigenin inhibited the growth of tumor in GBM xenograft mice model through inactivation of YAP. Taken together, these results suggest that irigenin exerts its anticancer effects on GBM via inhibiting YAP/β-catenin signaling, which may provide a new strategy for the treatment of GBM.
Hypertension related toxicity of chloroquine explains its failure against COVID-19: Based on rat model
Authors: Wang Junqi , Jing Xian , Hua Lizhong , Zheng Yuling , Hu Shiheng , Xiao Jing , Guo Dawei , Wu Wenda , Ji Hui , Peng Lin , Jiang Shanxiang , Gao Xiuge
Published: November 2022

Chloroquine was once thought to be a promising treatment for COVID-19 but it quickly failed due to its inefficiency and association with increased mortality. Further, comorbidities such as hypertension may have contributed this failure. The safety and toxicity of chloroquine at doses required for treating SARS-CoV-2 infection in hypertensive patients remain unknown. Herein, to investigate these effects, we performed a safety evaluation of chloroquine at the approved dose (63 mg/kg) and at a high dose (126 mg/kg) in hypertensive rats. We found that chloroquine increased the mortality of hypertensive rats to 18.2% and 100%, respectively, after 7 days. During the chloroquine exposure period, the bodyweight, feed, and water consumption of hypertensive rats were decreased significantly. In addition, we show that chloroquine induces prolongation of QTc interval, elevation of LDH and CK, and histopathological damage of the myocardium in hypertensive rats. Ocular toxicity was observed in hypertensive rats in the form of hemorrhage in the eyes and retinal damage. Furthermore, we also observed intestinal toxicity in hypertensive rats, which presented as thinning intestinal walls with hemorrhagic contents, and histopathological changes of the jejunum. Hepatotoxicity was also evidenced by elevated ALT, and vacuolization of hepatocytes was also observed. Nephrotoxicity was observed only in high dose chloroquine-treated hypertensive rats, presenting as alterations of urinalysis and renal function. Immune alterations were also found in high-dose chloroquine-treated hypertensive rats with elevation of serum IL-10, IL-1β and GRO, and moderate damage to the spleen. In summary, this study partially explains the reason for the failure of chloroquine as a COVID-19 therapy, and underlines the importance of safety evaluation and medical supervision of chloroquine to avoid patient harm, especially to those with hypertension.