bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome analysis of differentially expressed circRNAs miRNAs and mRNAs during the challenge of coccidiosis
Authors: Chen Xiaolan , Wang Zhijun , Chen Yangfeng , Akinci Ibrahim , Luo Wei , Xu Yibin , Jebessa Endashaw , Blake Damer , Sparks Nick , Hanotte Olivier , Nie Qinghua
Published: November 2022

Avian coccidiosis is a common enzootic disease caused by infection of Eimeria species parasites. It causes huge economic losses in the global poultry industry. Current control using anticoccidial drugs or vaccination is limited due to drug resistance and the relatively high cost of vaccines. Improving host genetic resistance to Eimeria species is considered an effective strategy for improved control of coccidiosis. Circular RNAs (circRNAs) have been found to function as biomarkers or diagnoses of various kinds of diseases. The molecular biological functions of circRNAs, miRNAs, and mRNAs related to Sasso chicken have not yet been described during Eimeria species challenge. In this study, RNA-seq was used to profile the expression pattern of circRNAs, miRNAs, and mRNAs in spleens from Eimeria tenella-infected and non-infected commercial dual-purpose Sasso T445 breed chickens. Results showed a total of 40 differentially expressed circRNAs (DEcircRNAs), 31 differentially expressed miRNAs (DEmiRNAs), and 820 differentially expressed genes (DEmRNAs) between infected and non-infected chickens. Regulatory networks were constructed between differentially expressed circRNAs, miRNAs, and mRNAs to offer insights into the interaction mechanisms between chickens and Eimeria spp. Functional validation of a significantly differentially expressed circRNA, circMGAT5, revealed that circMGAT5 could sponge miR-132c-5p to promote the expression of the miR-132c-5p target gene monocyte to macrophage differentiation-associated (MMD) during the infection of E. tenella sporozoites or LPS stimulation. Pathologically, knockdown of circMGAT5 significantly upregulated the expression of macrophage surface markers and the macrophage activation marker, F4/80 and MHC-II, which indicated that circMGAT5 might inhibit the activation of macrophage. miR-132c-5p markedly facilitated the expression of F4/80 and MHC-II while circMGAT5 could attenuate the increase of F4/80 and MHC-II induced by miR-132c-5p, indicating that circMGAT5 exhibited function through the circMGAT5-miR-132c-5p-MMD axis. Together, our results indicate that circRNAs exhibit their resistance or susceptive roles during E. tenella infection. Among these, circMGAT5 may inhibit the activation of macrophages through the circMGAT5-miR-132c-5p-MMD axis to participate in the immune response induced by Eimeria infection.
A methodology to uncertainty quantification of essential ocean variables
Authors: Waldmann Christoph , Fischer Philipp , Seitz Steffen , Köllner Manuela , Fischer Jens-Georg , Bergenthal Markus , Brix Holger , Weinreben Stefan , Huber Robert
Published: November 2022

The goal of this study is to provide a universally applicable procedure for a systematic evaluation of in situ measured data from single sensors regarding quantifying the uncertainty of the measurement results. As determining uncertainty for an environmental parameter also depends on the parameter itself, the focus here will be set on the variable water temperature in the first place. A separate analysis for salinity and other data will follow in later publications. With this first of a series of planned manuscripts on different parameters, we aim at providing a common understanding of how measurement uncertainty on single sensor measurements can be derived. Using an experimental in situ set-up with 6 different standard CTD sensors of two different brands, we created a four month-long, high-quality data set to be used to develop a reliable method for quantifying measurement uncertainties. Although the CTDs were deployed in a mooring in a coastal environment the described method can be extended to other deployment configurations as well. The described procedures have evolved as a stepwise process that takes the different perspectives of the involved authors into account, as well as the special conditions for environmental measurements, which are collected while the observed volume/area is undergoing a constant change. By sharing the ideas with other stakeholders, the basic concept can be extended to other observing programs and to other essential ocean variables.
Impact of progesterone-free luteal phase support following natural cycle frozen embryo transfer: Study protocol for a multicenter, non-inferiority, randomized controlled trial
Authors: Jiang Wen-Jing , Sun Zhen-Gao , Song Jing-Yan
Published: November 2022

Introduction

Nowadays, frozen-thawed embryo transfer (FET) has become one of the standard treatments for infertility in the field of assisted reproductive technology (ART). Natural cycle FET (NC-FET) has many advantages, such as simplicity and economics, no effect on patients’ menstrual cycles, estrogen and progesterone levels, as well as no interference in endometrial growth and transformation, which is aligned with the natural physiological state of embryo implantation. Nonetheless, there is a controversy regarding the need for luteal phase support (LPS) during NC-FET cycles. The purpose of this study is to assess whether LPS was not inferior to non-LPS in terms of OPR in NC-FET cycles.

Methods and analysis

This study including 1,010 ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles with an elective freeze-all strategy followed by NC-FET will be performed at four university-affiliated reproductive centers. Participants will be randomly assigned in a 1:1 ratio to receive LPS treatment or not. This study is designed as an open-label, non-inferiority, randomized controlled trial (RCT), and the primary statistical strategies were intention-to-treat (ITT) and per-protocol (PP) analysis.

Discussion

There may not have been any significant difference in the chance of a live birth after FET if no progesterone was supplemental during the luteal phase. However, due to the limited number of previous studies, which are mainly retrospective, evidence is still limited. Thus, by conducting this multicenter RCT, we intend to evaluate whether LPS is necessary in NC-FET.

Ethics and dissemination

A Reproductive Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (SDUTCM) has approved this study. This study will handle the data as required by general data protection regulations. Participants will sign a written informed consent regarding participation in the study and storage of blood samples in a biobank for future research. This study will be monitored by study personnel trained in Good Clinical Practice who are not involved in the study. The results of this study will be disseminated through publication in international peer-reviewed scientific journals.

Clinical trial registration

[https://www.chictr.org.cn/], identifier [ChiCTR2200057498].
Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227
Authors: Anderson Peter M. , Subbiah Vivek , Trucco Matteo M.
Published: November 2022

Osteosarcoma is a high-grade sarcoma characterized by osteoid formation, nearly universal expression of IGF1R and with a subset expressing HER-2. These qualities provide opportunities for the use of the alpha particle-emitting isotopes to provide targeted radiation therapy via alpha particles precisely to bone-forming tumors in addition to IFG1R or Her-2 expressing metastases. This review will detail experience using the alpha emitter radium-223 (223Ra, tradename Xofigo), that targets bone formation, in osteosarcoma, specifically related to patient selection, use of gemcitabine for radio-sensitization, and using denosumab to increasing the osteoblastic phenotype of these cancers. A case of an inoperable left upper lobe vertebral-paraspinal-mediastinal osteoblastic lesion treated successfully with 223Ra combined with gemcitabine is described. Because not all areas of osteosarcoma lesions are osteoblastic, but nearly all osteosarcoma cells overexpress IGF1R, and some subsets expressing Her-2, the anti-IGF1R antibody FPI-1434 linked to actinium-225 (225Ac) or the Her-2 antibody linked to thorium-227 (227Th) may become other means to provide targeted alpha particle therapy against osteosarcoma (NCT03746431 and NCT04147819).
Dynamic changes in myeloid-derived suppressor cells during the menstrual cycle: A pilot study
Authors: Xu Qiying , Liu Huifang , Qile Muge , Wuren Tana
Published: November 2022

Various studies have described the roles of myeloid-derived suppressor cells (MDSCs) in pathological conditions, but relatively few have described them under normal physiological conditions. Accumulation of MDSCs is important creating an anti-inflammation environment, which is essential for fertilized egg implantation. This study was designed to record the dynamic changes in MDSC-like cells composition during the menstrual period (MP) and ovulation period (OP) in healthy volunteers over the course of a single menstrual cycle to explore the association between MDSCs and the menstrual cycle under normal physiological conditions. The ratio of MDSC-like cells was higher in MP samples, whereas the activity of Arg-1 was higher during the OP window. There was a negative correlation between the ratio of MDSC-like cells and the percentage of lymphocytes and a positive correlation between MDSC-like cells and prostaglandin E2 (PGE2). Furthermore, regular changes in the ratio and function of MDSC-like cells in the peripheral blood were observed during menstruation, all of which corresponded to the cycle stage. During menstruation, MDSCs may promote endometrial repair, whereas they promote pregnancy during the OP. These findings may help to better understand the pathophysiology of pregnancy-related complications and lay a foundation for improving perinatal outcomes.
The role of FGF21 and its analogs on liver associated diseases
Authors: Falamarzi Kimia , Malekpour Mahdi , Tafti Mobin Fallah , Azarpira Negar , Behboodi Mehrdad , Zarei Mohammad
Published: November 2022

Fibroblast growth factor 21 (FGF21), a member of fibroblast growth factor family, is a hormone-like growth factor that is synthesized mainly in the liver and adipose tissue. FGF21 regulates lipid and glucose metabolism and has substantial roles in decreasing lipogenesis and increasing hepatic insulin sensitivity which causing lipid profile improvement. FGF21 genetic variations also affect nutritional and addictive behaviors such as smoking and alcohol consumption and eating sweets. The role of FGF21 in metabolic associated diseases like diabetes mellitus had been confirmed previously. Recently, several studies have demonstrated a correlation between FGF21 and liver diseases. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease worldwide. NAFLD has a wide range from simple steatosis to steatohepatitis with or without fibrosis and cirrhosis. Elevated serum levels of FGF21 associated with NAFLD and its pathogenesis. Alcoholic fatty liver disease (AFLD), another condition that cause liver injury, significantly increased FGF21 levels as a protective factor; FGF21 can reverse the progression of AFLD and can be a potential therapeutic agent for it. Also, NAFLD and AFLD are the most important risk factors for hepatocellular carcinoma (HCC) which is the fourth deadliest cancer in the world. Several studies showed that lack of FGF21 induced oncogenic condition and worsened HCC. In this review article, we intend to discuss different aspects of FGF21 in NAFLD, AFLD and HCC; including the role of FGF21 in pathophysiology of these conditions, the effects of FGF21 mutations, the possible use of the FGF21 as a biomarker in different stages of these diseases, as well as the usage of FGF21 and its analog molecules in the treatment of these diseases.
Outcome of keratolimbal allograft transplantation with deep anterior lamellar keratoplasty for bilateral limbal stem cell deficiency
Authors: Li Zongyuan , Yang Kunkun , Zhou Yannan , Wu Tengyun , Zhang Hongtao , Yang Qinghua , Wang Qun , Huang Yifei , Wang Liqiang
Published: November 2022

Objectives

To evaluate and compare the outcome of keratolimbal allograft (KLAL) transplantation with or without deep anterior lamellar keratoplasty (DALK) for bilateral severe limbal stem cell deficiency (LSCD).

Methods

This retrospective review included 49 eyes of 46 patients who underwent KLAL transplantation at the Department of Ophthalmology of Chinese PLA general hospital, 2009–2020, for bilateral severe LSCD were examined for corneal clarity and corneal scarring to determine whether to combine DALK with KLAL transplantation. Preoperative information, surgical decision tree, surgical procedures, and postoperative data were collected for each eye.

Results

All patients had preoperative severe or total LSCD. Twenty-four eyes underwent KLAL transplantation only, 25 KLAL transplantation plus DALK. The mean follow-up was 46.80 ± 31.22 months (18–158 months). Overall KLAL survival (with or without DALK) was 71.43% at the final follow-up (KLAL-only 66.67%, KLAL-DALK 76%). Kaplan–Meier survival analysis showed that the 3-year survival probability of all grafts was 70.53 ± 10.89% (KLAL-only 64.86 ± 10.11%, KLAL-DALK 75.79 ± 8.62%). The proportion of BCVA ≥ 20/200 eyes among all KLAL transplantations increased from 11 eyes (22.45%) preoperatively to 25 eyes (51.02%) after 1 year and 24 eyes (48.98%) at the last follow-up (P = 0.01). The proportion of BCVA ≥ 20/200 eyes in the KLAL-DALK group increased significantly (P = 0.04), from 16.0% at baseline to 48.0% after 1 year to 44.0% at the last follow-up. Seventeen eyes (34.69%) had postoperative complications.

Conclusion

KLAL-DALK is an effective option to restore a stable ocular surface and visual acuity rapidly in patients with bilateral, late-stage, severe LSCD.
Does cognitive frailty predict delayed neurocognitive recovery after noncardiac surgery in frail elderly individuals? Probably not
Authors: Zhang Jingya , Basnet Diksha , Du Xue , Yang Junjun , Liu Jiehui , Wu Fan , Zhang Xiaoqing , Liu Jianhui
Published: November 2022

Introduction

Delayed neurocognitive recovery (DNR) is a common post-surgical complication among the elderly. Cognitive frailty (CF) is also an age-related medical syndrome. However, little is known about the association between CF and DNR. Therefore, this study aimed to study whether CF is associated with DNR in elderly patients undergoing elective noncardiac surgery, as well as to explore the potential risk factors for DNR in frail elderly individuals and construct a prediction model.

Methods

This prospective cohort study administered a battery of cognitive and frailty screening instruments for 146 individuals (≥65 years old) scheduled for elective noncardiac surgery. Screening for CF was performed at least one day before surgery, and tests for the presence of DNR were performed seven days after surgery. The association between CF and DNR was investigated. Moreover, the study subjects were randomly divided into a modeling group (70%) and a validation group (30%). Univariate and multivariate logistic regression was performed to analyze the modeling group data and identify the independent risk factors for DNR. The R software was used to construct DNR's nomogram model, verifying the model.

Results

In total, 138 individuals were eligible. Thirty-three cases were diagnosed with DNR (23.9%). No significant difference in the number of patients with CF was observed between the DNR and non-DNR groups (P > 0.05). Multivariate analysis after adjusting relevant risk factors showed that only the judgment of line orientation (JLOT) test score significantly affected the incidence of DNR. After internal validation of the constructed DNR prediction model, the area under the curve (AUC) of the forecast probability for the modeling population (n = 97) for DNR was 0.801, and the AUC for the validation set (n = 41) was 0.797. The calibration curves of both the modeling and validation groups indicate that the prediction model has good stability.

Conclusion

Cognitive frailty is not an independent risk factor in predicting DNR after noncardiac surgery in frail elderly individuals. The preoperative JLOT score is an independent risk factor for DNR in frail elderly individuals. The prediction model has a good degree of discrimination and calibration, which means that it can individually predict the risk probability of DNR in frail elderly individuals.
Epileptic seizure first aid practices of publics in Northwest Ethiopia 2021: Unsafe practices of nearly three-fourths of the community
Authors: Asnakew Sintayehu , Legas Getasew , Belete Amsalu , Beyene Getnet Mihretie , Tedla Assasahegn , Shiferaw Kirubel , Mengist Birhanu , Bayih Wubet Alebachew , Feleke Dejen Getaneh , Birhane Binyam Minuye , Chanie Ermias Sisay , Birhan Zelalem , Birkie Mengesha , Yitbarek Getachew Yideg
Published: November 2022

Background

Religious and sociocultural beliefs influence how people with epilepsy (PWE) are treated and cared for. Many communities in Africa and other developing countries, including Ethiopia, believe that epilepsy is caused by evil spirits and should be treated with herbal plants by traditional doctors and religious leaders. The combination of these sociocultural beliefs and the level of community awareness of epilepsy affect first aid practices in the management of epileptic seizures.

Objective

This study aimed to assess epileptic seizure first aid practice of public and its associated factors in Northwest Ethiopia, south Gondar zone, Amhara, Ethiopia 2021.

Methods

A community-based cross-sectional study was conducted using a previously adapted standard questionnaire. A multistage cluster sampling technique was applied. A total of 756 participants were approached and 741 respondents completed the questionnaire with a response rate of 98.02%. Data were entered into Epi data version 4.4.2 and then exported to Statistical Package for Social Science (SPSS) version 24 for analysis. Descriptive and analytical statistical procedures and bivariable and multivariable binary logistic regressions with odds ratios and 95% confidence interval (CI) were employed. The level of significance of the association was determined at p < 0.05.

Results

Overall, 71.7% (95%CI: 68.3, 74.9) of the south Gondar community had unsafe practice measures in managing patients with seizure episodes. Individuals who were illiterate [adjusted odd ratio (AOR) = 1.99, 95%CI: 1.00.3.97] and participants who did not take training related to epilepsy (AOR = 2.07, 95%CI: 1.35, 3.17) and had poor knowledge about (AOR = 1.51, 95%CI: 1.06, 2.14) and a negative attitude toward epilepsy (AOR = 2.20, 95%CI: 1.50, 3.22) had unsafe practices compared to their counterparts. Conversely, participants who reached secondary education had safe practice measures (AOR = 0.4, 95%CI: 0.26, 0.63) in the management of epileptic seizures.

Conclusions

In this study, large numbers of the south Gondar community had unsafe practice measures in managing people with epileptic seizure episodes. Greater emphasis should be laid on individuals who were illiterate, in the provision of health education and/or training for the community to help them to acquire good knowledge about epilepsy and develop a positive attitude toward epilepsy.
Case report: Non-Alzheimer's disease tauopathy with logopenic variant primary progressive aphasia diagnosed using amyloid and tau PET
Authors: Momota Yuki , Konishi Mika , Takahata Keisuke , Kishimoto Taishiro , Tezuka Toshiki , Bun Shogyoku , Tabuchi Hajime , Ito Daisuke , Mimura Masaru
Published: November 2022

We report a patient with logopenic variant primary progressive aphasia (lv-PPA) who was diagnosed as having non-Alzheimer's disease (AD) tauopathy after multiple biophysical/biological examinations, including amyloid and 18F-florzolotau tau positron emission tomography (PET), had been performed. A woman in her late 60s who had previously been diagnosed as having AD was referred to us for a further, detailed examination. She had been unaware of any symptoms at the time of AD diagnosis, but she subsequently became gradually aware of a speech impairment. She talked nearly completely and fluently, although she occasionally exhibited word-finding difficulty and made phonological errors during naming, word fluency testing, and sentence repetition; these findings met the criteria for the diagnosis of lv-PPA, which is known to be observed more commonly in AD than in other proteinopathies. Magnetic resonance imaging, single photon emission computed tomography, and plasma phosphorylated tau and plasma neurofilament light chain measurements showed an AD-like pattern. However, both 11C-Pittsburgh compound-B and 18F-florbetaben amyloid PET showed negative results, whereas 18F-florzolotau tau PET yielded positive results, with radio signals predominantly in the left superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and frontal operculum. Whole-genome sequencing revealed no known dominantly inherited mutations in AD or frontotemporal lobar degeneration genes, including the genes encoding amyloid precursor protein, microtubule-associated protein tau, presenilin 1 and 2. To the best of our knowledge, this patient was a rare case of lv-PPA who was diagnosed as having non-AD tauopathy based on the results of multiple examinations, including whole-genome sequencing, plasma measurement, and amyloid and 18F-florzolotau tau PET. This case underscores the clinicopathologically heterogeneous nature of this syndrome.
Remote ischemic conditioning (RIC) with exercise (RICE) is safe and feasible for acute ischemic stroke (AIS) patients
Authors: Tong Yanna , Lee Hangil , Kohls Wesley , Han Zhenzhen , Duan Honglian , Cheng Zhe , Li Fenghai , Gao Jie , Liu Jing , Geng Xiaokun , Ding Yuchuan
Published: November 2022

Objective

Rehabilitation is essential in reducing stroke disability and should be performed as early as possible. Exercise is an established and effective rehabilitation method; however, its implementation has been limited as its very early use exacerbates cerebral injury and is restricted by patients' unstable conditions and disabilities. Remote ischemic conditioning (RIC) is a passive and accessible therapy in acute phases of stroke and appears to have similar neuroprotective effects as exercise. This study assessed the safety and feasibility of the novel rehabilitation strategy—early RIC followed by exercise (RICE) in acute ischemic stroke (AIS).

Methods

We conducted a single-center, double-blinded, randomized controlled trial with AIS patients within 24 h of stroke onset or symptom exacerbation. All enrolled patients were randomly assigned, at a ratio of 1:1, to either the RICE group or the sham-RICE group (sham RIC with exercise). Each group received either RIC or sham RIC within 24 h after stroke onset or symptom exacerbation, once a day, for 14 days. Both groups started the exercise routine on day 4, twice daily, for 11 total days. The safety endpoints included clinical deterioration, recurrence of stroke, hemorrhagic transformation, complications, and adverse events resulting from RICE during hospitalization. The efficacy endpoints [Modified Rankin Scale (mRS) score, National Institutes of Health Stroke Scale (NIHSS) score, Barthel Index, and walking ability] were evaluated at admission and 90 days after stroke onset.

Results

Forty AIS patients were recruited and completed the study. No significant differences in baseline characteristics were found between the two groups, which included risk factors, stroke severity at admission, pre-morbid disability, and other special treatments. No significant differences were found in the safety endpoints between two groups. Excellent recovery (mRS 0–2) at 3 months was obtained in 55% of the patients with RICE as compared 40% in sham group, but it did not reach a significant level.

Conclusions

RICE was safe and feasible for AIS patients, and seems to be a promising early stroke rehabilitation. The results of this study suggest a need for a future randomized and controlled multicenter trial with a larger sample size to determine the efficacy of RICE.
Language input in late infancy scaffolds emergent literacy skills and predicts reading related white matter development
Authors: Weiss Yael , Huber Elizabeth , Ferjan Ramírez Naja , Corrigan Neva M. , Yarnykh Vasily L. , Kuhl Patricia K.
Published: November 2022

Longitudinal studies provide the unique opportunity to test whether early language provides a scaffolding for the acquisition of the ability to read. This study tests the hypothesis that parental language input during the first 2 years of life predicts emergent literacy skills at 5 years of age, and that white matter development observed early in the 3rd year (at 26 months) may help to account for these effects. We collected naturalistic recordings of parent and child language at 6, 10, 14, 18, and 24 months using the Language ENvironment Analysis system (LENA) in a group of typically developing infants. We then examined the relationship between language measures during infancy and follow-up measures of reading related skills at age 5 years, in the same group of participants (N = 53). A subset of these children also completed diffusion and quantitative MRI scans at age 2 years (N = 20). Within this subgroup, diffusion tractography was used to identify white matter pathways that are considered critical to language and reading development, namely, the arcuate fasciculus (AF), superior and inferior longitudinal fasciculi, and inferior occipital-frontal fasciculus. Quantitative macromolecular proton fraction (MPF) mapping was used to characterize myelin density within these separately defined regions of interest. The longitudinal data were then used to test correlations between early language input and output, white matter measures at age 2 years, and pre-literacy skills at age 5 years. Parental language input, child speech output, and parent-child conversational turns correlated with pre-literacy skills, as well as myelin density estimates within the left arcuate and superior longitudinal fasciculus. Mediation analyses indicated that the left AF accounted for longitudinal relationships between infant home language measures and 5-year letter identification and letter-sound knowledge, suggesting that the left AF myelination at 2 years may serve as a mechanism by which early language experience supports emergent literacy.
The regulatory role of endoplasmic reticulum chaperone proteins in neurodevelopment
Authors: Sun Hongji , Wu Mengxue , Wang Minxin , Zhang Xiaomin , Zhu Jia
Published: November 2022

The endoplasmic reticulum (ER) is the largest tubular reticular organelle spanning the cell. As the main site of protein synthesis, Ca2+homeostasis maintenance and lipid metabolism, the ER plays a variety of essential roles in eukaryotic cells, with ER molecular chaperones participate in all these processes. In recent years, it has been reported that the abnormal expression of ER chaperones often leads to a variety of neurodevelopmental disorders (NDDs), including abnormal neuronal migration, neuronal morphogenesis, and synaptic function. Neuronal development is a complex and precisely regulated process. Currently, the mechanism by which neural development is regulated at the ER level remains under investigation. Therefore, in this work, we reviewed the recent advances in the roles of ER chaperones in neural development and developmental disorders caused by the deficiency of these molecular chaperones.
The association of dietary glutamine supplementation with the development of high salt-induced hypertension in rats
Authors: Yang Liu , Xu Longjin , Li Juan , Wang Huan , Sun Jiahong , Yu Ziqiang , Zhao Xiaoqian , Zhao Min , Xi Bo
Published: November 2022

Glutamine supplementation has been reported to affect blood pressure (BP). However, its role in the progression of hypertension induced by high salt diet (HSD) has not been elucidated. Male normotensive Wistar rats were exposed to high salt diet and treated with different doses of glutamine supplementation. Rats aged 6 weeks were assigned to five groups: (1) Normal-salt diet (0.3% NaCl, NSD); (2) High-salt diet (8% NaCl, HSD); (3) High-salt + low-dose diet (8% NaCl, 0.5 g of L-glutamine/kg body weight, HSLGD); (4) High-salt + middle-dose diet (8% NaCl, 1.5 g of L-glutamine/kg body weight, HSMGD); and (5) High-salt + high-dose diet (8% NaCl, 2.5 g of L-glutamine/kg body weight, HSHGD). After supplementing different doses of glutamine to male Wistar 6-week-old rats fed with HSD for 7 weeks, we found no difference in body weight among groups. Importantly, we showed that dietary L-glutamine supplementation could prevent the development of hypertension in a dose-dependent manner [dramatically lowering systolic blood pressure (SBP) and slightly reducing diastolic blood pressure (DBP) of hypertensive rats, while the differences of DBP between groups did not reach statistical significance]. Our data further elucidated that dietary glutamine supplementation mildly alleviated the degree of left ventricular hypertrophy, including interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in hypertensive rats. Together, our results offer evidence that the dietary uptake of glutamine may be associated with attenuating the development of high salt-induced hypertension and slightly alleviating the degree of left ventricular hypertrophy in hypertensive rats. Therefore, glutamine supplementation may act as a prospective dietary intervention for the treatment of hypertension.
The combination of phase angle and age has a good diagnostic value for sarcopenia in continuous ambulatory peritoneal dialysis patients
Authors: Chen Ye , Wu Jinlan , Ran Lei , Yu Dan , Chen Xi , Liu Maodong
Published: November 2022

Aims

There are limited studies on phase angle and sarcopenia in continuous ambulatory peritoneal dialysis patients. So, we want to explore the association between phase angle and sarcopenia and find a more sensitive indicator for diagnosing sarcopenia.

Methods

We included 101 continuous ambulatory peritoneal dialysis patients from March 2022 to August 2022 and measured the phase angle and body composition by bioelectrical impedance analysis. All patients had their handgrip strength measured. Then, we divided patients into the sarcopenia (n = 30) group and non-sarcopenia (n = 71) group according to the sarcopenia diagnostic strategy formulated by the Asian Working Group for Sarcopenia. We used logistic regression to explore the risk factors of sarcopenia. We applied Receiver-operating characteristics curves to determine the diagnostic accuracy of these risk factors.

Results

After adjustments for sex, age, diabetes, BMI, extracellular water ratio, extra water, serum creatinine, total kt/v, and residual kt/v, phase angle correlated to handgrip strength and lowered limb muscle mass but not to skeletal muscle mass, upper arm muscle circumference, upper limb muscle mass and appendicular skeletal muscle mass index. In the multivariate logistic model, low phase angle and older age are risk factors for sarcopenia. The AUROC of phase angle for sarcopenia is 0.79 (95%CI, 0.70–0.86, P < 0.01) for both sexes, 0.70 and 0.85 for females and males. After we combined age and phase angle as diagnostic indicators of sarcopenia, the AUROC is 0.91 (95%CI, 0.83–0.96, P < 0.0001) in both sexes, 0.89 and 0.93 for females and males.

Conclusion

This study illustrates that age 52 or older is an independent risk factor for sarcopenia in continuous ambulatory peritoneal dialysis patients. Phase angle can act as a predictor of sarcopenia in those patients. But the combination of age and phase angle is more valuable in diagnosing sarcopenia.
Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention
Authors: Saris Christiaan G. J. , Timmers Silvie
Published: November 2022

Ketogenic diets and orally administered exogenous ketone supplements are strategies to increase serum ketone bodies serving as an alternative energy fuel for high energy demanding tissues, such as the brain, muscles, and the heart. The ketogenic diet is a low-carbohydrate and fat-rich diet, whereas ketone supplements are usually supplied as esters or salts. Nutritional ketosis, defined as serum ketone concentrations of ≥ 0.5 mmol/L, has a fasting-like effect and results in all sorts of metabolic shifts and thereby enhancing the health status. In this review, we thus discuss the different interventions to reach nutritional ketosis, and summarize the effects on heart diseases, epilepsy, mitochondrial diseases, and neurodegenerative disorders. Interest in the proposed therapeutic benefits of nutritional ketosis has been growing the past recent years. The implication of this nutritional intervention is becoming more evident and has shown interesting potential. Mechanistic insights explaining the overall health effects of the ketogenic state, will lead to precision nutrition for the latter diseases.
Automated lesion detection of breast cancer in [18F] FDG PET/CT using a novel AI-Based workflow
Authors: Leal Jeffrey P. , Rowe Steven P. , Stearns Vered , Connolly Roisin M. , Vaklavas Christos , Liu Minetta C. , Storniolo Anna Maria , Wahl Richard L. , Pomper Martin G. , Solnes Lilja B.
Published: November 2022

Applications based on artificial intelligence (AI) and deep learning (DL) are rapidly being developed to assist in the detection and characterization of lesions on medical images. In this study, we developed and examined an image-processing workflow that incorporates both traditional image processing with AI technology and utilizes a standards-based approach for disease identification and quantitation to segment and classify tissue within a whole-body [18F]FDG PET/CT study.

Methods

One hundred thirty baseline PET/CT studies from two multi-institutional preoperative clinical trials in early-stage breast cancer were semi-automatically segmented using techniques based on PERCIST v1.0 thresholds and the individual segmentations classified as to tissue type by an experienced nuclear medicine physician. These classifications were then used to train a convolutional neural network (CNN) to automatically accomplish the same tasks.

Results

Our CNN-based workflow demonstrated Sensitivity at detecting disease (either primary lesion or lymphadenopathy) of 0.96 (95% CI [0.9, 1.0], 99% CI [0.87,1.00]), Specificity of 1.00 (95% CI [1.0,1.0], 99% CI [1.0,1.0]), DICE score of 0.94 (95% CI [0.89, 0.99], 99% CI [0.86, 1.00]), and Jaccard score of 0.89 (95% CI [0.80, 0.98], 99% CI [0.74, 1.00]).

Conclusion

This pilot work has demonstrated the ability of AI-based workflow using DL-CNNs to specifically identify breast cancer tissue as determined by [18F]FDG avidity in a PET/CT study. The high sensitivity and specificity of the network supports the idea that AI can be trained to recognize specific tissue signatures, both normal and disease, in molecular imaging studies using radiopharmaceuticals. Future work will explore the applicability of these techniques to other disease types and alternative radiotracers, as well as explore the accuracy of fully automated and quantitative detection and response assessment.
Consistent downregulation of the cleft lip/palate-associated genes IRF6 and GRHL3 in carcinomas
Authors: Parisi Ludovica , Mockenhaupt Carolin , Rihs Silvia , Mansour Farah , Katsaros Christos , Degen Martin
Published: November 2022

Interferon Regulatory Factor 6 (IRF6) and Grainyhead Like Transcription Factor 3 (GRHL3) are transcription factors that orchestrate gene regulatory networks required for the balance between keratinocyte differentiation and proliferation. Absence of either protein results in the lack of a normal stratified epidermis with keratinocytes failing to stop proliferating and to terminally differentiate. Numerous pathological variants within IRF6 and GRHL3 have been identified in orofacial cleft-affected individuals and expression of the two transcription factors has been found to be often dysregulated in cancers. However, whether orofacial cleft-associated IRF6 and GRHL3 variants in patients might also affect their cancer risk later in life, is not clear yet. The fact that the role of IRF6 and GRHL3 in cancer remains controversial makes this question even more challenging. Some studies identified IRF6 and GRHL3 as oncogenes, while others could attribute tumor suppressive functions to them. Trying to solve this apparent conundrum, we herein aimed to characterize IRF6 and GRHL3 function in various types of carcinomas. We screened multiple cancer and normal cell lines for their expression, and subsequently proceeded with functional assays in cancer cell lines. Our data uncovered consistent downregulation of IRF6 and GRHL3 in all types of carcinomas analyzed. Reduced levels of IRF6 and GRHL3 were found to be associated with several tumorigenic properties, such as enhanced cell proliferation, epithelial mesenchymal transition, migration and reduced differentiation capacity. Based on our findings, IRF6 and GRHL3 can be considered as tumor suppressor genes in various carcinomas, which makes them potential common etiological factors for cancer and CLP in a fraction of CLP-affected patients.
Efficacy and safety of belantamab-mafodotin in triple-refractory multiple myeloma patients: A multicentric real-life experience
Authors: Iula Rossella , De Novellis Danilo , Trastulli Fabio , Della Pepa Roberta , Fontana Raffaele , Carobene Angela , Di Perna Maria , D’Ambrosio Alessandro , Romano Martina , Leone Aldo , De Fazio Laura , Fiumarella Alfonso , Gaeta Giuseppe , Marafioti Violetta , Barbato Serafina , Palmieri Salvatore , Rocco Stefano , Serio Bianca , Califano Catello , Pane Fabrizio , Ferrara Felicetto , Giudice Valentina , Selleri Carmine , Catalano Lucio
Published: November 2022

Belantamab-mafodotin is an innovative and selective treatment for multi-refractory/relapsed multiple myeloma (MM) patients; however, available real-life experiences on efficacy and safety are limited. In this real-world multicentric retrospective study, we enrolled 28 MM patients treated in four Hematology units of Campania region, Italy, who received a median of six treatment lines prior to belantamab-mafodotin. The overall response rate (ORR) was 40% (complete remission, CR, 11%; very good partial remission, VGPR, 11%; and partial remission, PR, 18%), with a median progression-free survival (PFS) and overall survival (OS) of 3 and 8 months, respectively. One of the most frequent drug-related adverse events was keratopathy observed in nine (32%) patients, leading to therapy discontinuation in only three (11%) of them. Moreover, 22 out of 28 total patients who were treated with at least two administrations achieved an ORR of 50% (CR, 14%; VGPR, 14%; and PR, 22%) with a median PFS and OS of 5 and 11 months, respectively. In conclusion, our multicentric study confirmed efficacy and safety of belantamab-mafodotin in triple-refractory MM patients even in the real-life setting.
Accuracy of novel urinary biomarker tests in the diagnosis of prostate cancer: A systematic review and network meta-analysis
Authors: Wang Leibo , He Wei , Shi Guanyu , Zhao Guoqiang , Cen Zhuangding , Xu Feng , Tian Wu , Zhao Xin , Mo Chishou
Published: November 2022

Objective

The purpose of this study was to conduct a network meta-analysis comparing the diagnostic value of different urinary markers for prostate cancer.

Methods

As of June 2022, the literature was retrieved by searching Pubmed, EMBASE, Web of Science databases and other databases. The methodological quality of included studies was assessed using the Cochrane Collaboration’s risk of bias tool, and publication bias was assessed using funnel plots. The surface under the cumulative ranking curve (SUCRA) values ​​was used to determine the most effective diagnostic method and the data were analyzed accordingly using data analysis software.

Results

A total of 16 articles was included including 9952 patients. The ranking results of network meta-analysis showed that the diagnostic performance of the four urine markers Selectmdx, MIPS, PCA3 and EPI was better than that of PSA. Among them, the specificity, positive predictive value and diagnostic accuracy of Selectmdx ranked first in the SUCRA ranking (SUCRA values: 85.2%, 88.3%, 97.1%), and the sensitivity ranked second in the SUCRA ranking (SUCRA value: 54.4%), and the negative predictive value ranked fourth in SUCRA (SUCRA value: 51.6%). The most sensitive screening tool was MIPS (SUCRA value: 67.1%), and it was also the second screening tool ranked higher in specificity, positive predictive value, negative predictive value and diagnostic accuracy (SUCRA value: 56.5%, respectively)., 57.1%, 67.9%, 74.3%). The high negative predictive value SUCRA ranking is EPI (SUCRA value: 68.0%), its sensitivity ranks third (SUCRA value: 45.6%), and its specificity, positive predictive value and diagnostic accuracy are ranked fourth (SUCRA values are: 45%, 38.2%, 35.8%).

Conclusion

According to the network ranking diagram, we finally concluded that Selectmdx and MIPS can be used as the most suitable urine markers for prostate cancer screening and diagnosis. To further explore the diagnostic value of different urinary markers in the screening of PCa patients.

Systematic Review Registration

https://inplasy.com/, identifier INPLASY202290094.
Review of experimental investigations of wings in ground effect at low Reynolds numbers
Authors: Lee T. , Lin G.
Published: November 2022

The ground effect-induced large lift increase and lift-induced drag reduction have long been recognized and utilized in the design and construction of wing-in-ground effect (WIG) craft. Various wing planforms have been employed in WIG craft. In this study, the experimental investigations of rectangular wings and delta wings of reverse and regular configurations at low Reynolds numbers are reviewed. For rectangular wings, both chord-dominated and span-dominated ground effects on the aerodynamics, tip vortex, and lift-induced drag are reviewed. For reverse delta wings, in addition to the experimental measurements of the aerodynamics and tip vortex flow at different ground distances, passive flow control utilizing Gurney flap, cropping, and anhedral are reviewed. The impact of ground effect on delta wings is also discussed. Suggestions for future investigations applicable to each wing planform in-ground effect are provided.
Impact of the herbal medicine, Ephedra sinica stapf, on gut microbiota and body weight in a diet-induced obesity model
Authors: Song Eun-Ji , Shin Na Rae , Jeon Songhee , Nam Young-Do , Kim Hojun
Published: November 2022

Obesity is a chronic metabolic disease caused by excessive body fat and has become a global public health problem. Evidence suggests that obesity and obesity-induced metabolic disorders are closely related to gut microbiota. Bupropion (BP), an antidepressant medicine, and Ephedra sinica Stapf [Ephedraceae; Ephedrae Herba], a herbal medicine, are sympathetic stimulants and have weight loss effects. However, to our best knowledge, no studies have simultaneously assessed the effects of drugs and herbal medicines on obesity and gut microbiota. This study aimed to determine the effects of BP and ES on weight loss and re-modulation of host gut microbiota. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet supplemented with bupropion (BP; 30 mg/kg/day) and Ephedra sinica Stapf extract (ES; 150 mg/kg/day) via oral gavage for eight weeks. Further, we evaluated the effects of BP and ES on body weight and fat accumulation. In addition, we evaluated the effects of BP and ES on gut microbiota using 16S rRNA amplicon sequencing. Our results showed that weight loss was confirmed in both BP and ES; however, it was more pronounced in ES. ES changed the overall composition of the gut microbiota by restoring the relative abundance of Oscillospiraceae, Lachnospiraceae, and the Firmicutes/Bacteroidetes ratio, an indicator of gut microbiota dysbiosis. Nine amplicon sequence variants (ASVs) of the gut microbiome were significantly recovered by BP and ES treatment, of which eight ASVs correlated with body weight and fat accumulation. Additionally, three ASVs were significantly recovered by ES treatment alone. In conclusion, the anti-obesity effects of BP and ES, especially fat accumulation, are related to the regulation of gut microbiota. Moreover, ES had a greater influence on the gut microbiota than BP.
Intrapericardial cardiosphere-derived cells hinder epicardial dense scar expansion and promote electrical homogeneity in a porcine post-infarction model
Authors: Carta-Bergaz Alejandro , Ríos-Muñoz Gonzalo R. , Crisóstomo Verónica , Sánchez-Margallo Francisco M. , Ledesma-Carbayo María J. , Bermejo-Thomas Javier , Fernández-Avilés Francisco , Arenal-Maíz Ángel
Published: November 2022

The arrhythmic substrate of ventricular tachycardias in many structural heart diseases is located in the epicardium, often resulting in poor outcomes with currently available therapies. Cardiosphere-derived cells (CDCs) have been shown to modify myocardial scarring. A total of 19 Large White pigs were infarcted by occlusion of the mid-left anterior descending coronary artery for 150 min. Baseline cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement sequences was obtained 4 weeks post-infarction and pigs were randomized to a treatment group (intrapericardial administration of 300,000 allogeneic CDCs/kg), (n = 10) and to a control group (n = 9). A second CMR and high-density endocardial electroanatomical mapping were performed at 16 weeks post-infarction. After the electrophysiological study, pigs were sacrificed and epicardial optical mapping and histological studies of the heterogeneous tissue of the endocardial and epicardial scars were performed. In comparison with control conditions, intrapericardial CDCs reduced the growth of epicardial dense scar and epicardial electrical heterogeneity. The relative differences in conduction velocity and action potential duration between healthy myocardium and heterogeneous tissue were significantly smaller in the CDC-treated group than in the control group. The lower electrical heterogeneity coincides with heterogeneous tissue with less fibrosis, better cardiomyocyte viability, and a greater quantity and better polarity of connexin 43. At the endocardial level, no differences were detected between groups. Intrapericardial CDCs produce anatomical and functional changes in the epicardial arrhythmic substrate, which could have an anti-arrhythmic effect.
Potential allopolyploid origin of Ericales revealed with gene-tree reconciliation
Authors: Nie Shuai , Tian Xue-Chan , Kong Lei , Zhao Shi-Wei , Chen Zhao-Yang , Jiao Si-Qian , El-Kassaby Yousry A. , Porth Ilga , Yang Fu-Sheng , Zhao Wei , Mao Jian-Feng
Published: November 2022

Few incidents of ancient allopolyploidization (polyploidization by hybridization or merging diverged genomes) were previously revealed, although there is significant evidence for the accumulation of whole genome duplications (WGD) in plants. Here, we focused on Ericales, one of the largest and most diverse angiosperm orders with significant ornamental and economic value. Through integrating 24 high-quality whole genome data selected from ~ 200 Superasterids genomes/species and an algorithm of topology-based gene-tree reconciliation, we explored the evolutionary history of in Ericales with ancient complex. We unraveled the allopolyploid origin of Ericales and detected extensive lineage-specific gene loss following the polyploidization. Our study provided a new hypothesis regarding the origin of Ericales and revealed an instructive perspective of gene loss as a pervasive source of genetic variation and adaptive phenotypic diversity in Ericales.