bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic evaluation of high-risk stone formers: a retrospective study
Authors: Parajuli Purushottam , Luitel Bhoj Raj , Pradhan Manish Man , Chapagain Suman , Poudyal Sujeet , Chalise Pawan Raj , Sharma Uttam Kumar , Gyawali Prem Raj
Published: January 2023

Background

The purpose of this study was to assess the metabolic abnormalities in high-risk stone formers.

Methods

This was a retrospective observational study done at Tribhuvan University Teaching Hospital, Nepal, over 1-year period. High-risk stone formers were identified and were evaluated with serum chemistries and 24-h urinary chemical evaluation. Stone analysis was also included whenever available. Common metabolic abnormalities and stone analysis results were reported and compared with different studies. Continuous variables were expressed as mean ± SD. Categorical variables were expressed as percentage and proportions.

Results

During 1 year of period, sixty-five patients had undergone extensive metabolic evaluation, but complete data were available for only forty-six patients. Of the total patients (n = 46), 63% were male (n = 29) and rest (36.9%) were female. Mean age of patients was 34.4 ± 15.1 years. Common reasons for metabolic evaluation were multiple stones (40%), bilateral stones (27%), recurrent stones (17%) and others (16%). Most common stone type was mixed stone with predominant composition being calcium oxalate mono- and dihydrate (62.9%). Twenty-four-hour urinary metabolic evaluation showed hyperoxaluria (32.6%) as most common abnormalities followed by hypocitraturia (21.7%) and hypocalciuria (21.7%).

Conclusion

Hyperoxaluria and hypocitraturia are common metabolic abnormalities in our patients. These findings help in counselling dietary measures to patients.
Detection of the local adaptive and genome-wide associated loci in southeast Nigerian taro (Colocasia esculenta (L.) Schott) populations
Authors: Fufa Tilahun Wondimu , Menamo Temesgen Matiwos , Abtew Wosene Gebreselassie , Amadi Charles Okechukwu , Oselebe Happiness Ogba
Published: January 2023

Background

Taro has a long history of being consumed and remains orphan and on the hand Nigeria farmers. The role of farmer-driven artificial selection is not negligible to fit landraces to a particular ecological condition. Limited study has been conducted on genome-wide association and no study has been conducted on genome-environment association for clinal adaptation for taro. Therefore, the objective of this study was to detect loci that are associated with environmental variables and phenotype traits and forward input to breeders. The study used 92 geographical referred taro landraces collected from Southeast (SE) Nigeria.

Results

The result indicates that SE Nigerian taro has untapped phenotype and genetic variability with low admixture. Redundancy analysis indicated that collinear explained SNP variation more than single climatic variable. Overall, the results indicated that no single method exclusively was able to capture population confounding effects better than the others for all six traits. Nevertheless, based on overall model performance, Blink seemed to provide slight advantage over other models and was selected for all subsequent assessment of genome-environment association (GEA) and genome-wide association study (GWAS) models. Genome scan and GEA identified local adapted loci and co-located genes. A total of nine SNP markers associated with environmental variables. Some of the SNP markers (such as S_101024366) co-located with genes which previously reported for climatic adaptation such as astringency, diaminopimelate decarboxylase and MYB transcription factor. Genome-wide association also identified 45, 40 and 34 significant SNP markers associated with studied traits in combined, year 1 and year 2 data sets, respectively. Out of these, five SNP markers (S1_18891752 S3_100795476, S1_100584471 S1_100896936 and S2_10058799) were consistent in two different data sets.

Conclusions

The findings from this study improve our understanding of the genetic control of adaptive and phenotypic traits in Nigerian taro. However, the study suggests further study on identification of local adaptive loci and GWAS through collection of more landraces throughout the country, and across different agro-ecologies.
Expression patterns and prognostic value of key regulators associated with m7G RNA modification based on all gene expression in colon adenocarcinoma
Authors: Zhu Yuanchang , Zhao Zeyi , Thandar Mya , Cheng Junhao , Chi Pan , Huang Shenghui
Published: January 2023

Background

N7-methylguanosine (m7G) is present in a wide variety of organisms and has important roles. m7G has been reported to be involved in multiple biological processes, and recent studies have reported that changes in RNA modifications result in tumor cellular transformation and cancer, such as colon adenocarcinoma, lung cancer, and intrahepatic cholangiocarcinoma. However, little is known about the function of the m7G in colon adenocarcinoma.

Methods

We established two clusters based on the expression of all genes associated with m7G to explore the expression pattern of 31 key regulatory factors of m7G RNA and assess the prognostic value of regulatory factors. Wilcoxon test and differential box line plots were applied for bioinformatics analysis. Receiver Operating and Kaplan‒Meier curves were utilized to evaluate the prognostic value. Finally, four genes' expression in the colon cancer cell line was confirmed by qRT-PCR.

Results

From The Cancer Genome Atlas database, we found that the expression levels of 25 out of the 31 key N7-methylguanosine RNA modification regulators were significantly different in colon adenocarcinoma. According to 25 methylation regulators’ expression, we identified two subgroups by consensus clustering, in which the prognosis was worse in Group 2 than in Group 1 and was significantly correlated with age. Cluster 2 was significantly enriched in tumor-associated pathways, and immune cells were highly infiltrated in Cluster 1 but weakly infiltrated in Cluster 2. Further results indicated that this risk profile may serve as a standalone predictive factor for colon adenocarcinoma, and the four genetic risk profiles’ prognostic relatedness was successfully verified through Gene Expression Omnibus dataset. At last, A nomogram for prognosis was created according to age, sex, histological grading, clinicopathological staging, and hazard score to accurately predict patient prognosis in colon adenocarcinoma. We successfully validated the differential expression of four genes using qRT-PCR.

Conclusions

In the present study, we revealed the important contribution of key regulators associated with m7G RNA modifications based on all gene expression in colon adenocarcinoma and developed a signature of risk that serves as a promising prognostic marker for patients with colon adenocarcinoma.
Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV
Authors: Dold Leona , Nielsen Mette J. , Praktiknjo Michael , Schwarze-Zander Carolynne , Boesecke Christoph , Wasmuth Jan-Christian , Bischoff Jenny , Rockstroh Jürgen Kurt , Karsdal Morten A. , Spengler Ulrich , Trebicka Jonel , Strassburg Christian P. , Leeming Diana J. , Langhans Bettina
Published: January 2023

Background and aims

Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis.

Methods

This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA.

Results

Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis.

Conclusion

Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease.
COVID-19 associated acute transplant failure after AB0-incompatible living donor kidney transplantation – a case report
Authors: Boss Kristina , Konik Margarethe , Bräsen Jan Hinrich , Schmitz Jessica , Jürgens Christiane , Kribben Andreas , Witzke Oliver , Dolff Sebastian , Gäckler Anja
Published: January 2023

Introduction

Immunosuppressive therapy is associated with an increased risk of severe courses of SARS-CoV-2 infection, with frequently delayed viral clearance. We report a case of an acute kidney transplant failure in persistent SARS-CoV-2 infection in a patient with absolute B-cell depletion after administration of rituximab for AB0-incompatible living donor kidney transplantation.

Case presentation

A 34-year-old unvaccinated patient is diagnosed with SARS-CoV-2 infection four months after kidney transplantation. With only mild symptoms and an estimated glomerular filtration rate (eGFR) of 44 ml/min/1.73 m2, therapy with molnupiravir was initially given. Within the next eight weeks, transplant biopsies were performed for acute graft failure. These showed acute T-cell rejection with severe acute tubular epithelial damage with only mild interstitial fibrosis and tubular atrophy (BANFF cat. 4 IB), and borderline rejection (BANFF cat. 3). A therapy with prednisolone and intravenous immunoglobulins was performed twice. With unchanged graft failure, the third biopsy also formally showed BANFF cat. 4 IB. However, fluorescence in situ hybridization detected SARS-CoV-2 viruses in large portions of the distal tubules. After nine weeks of persistent COVID-19 disease neither anti-SARS-CoV-2 IgG nor a SARS-CoV-2-specific cellular immune response could be detected, leading to the administration of sotrovimab and remdesivir. Among them, SARS-CoV-2 clearance, detection of IgG, and improvement of graft function were achieved.

Conclusion

Lack of viral clearance can lead to complications of SARS-CoV-2 infection with atypical manifestations. In kidney transplant patients, before initiating therapy, the differential diagnoses of “rejection” and “virus infection” should be weighed against each other in an interdisciplinary team of nephrologists, infectious diseases specialists and pathologists.
C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis
Authors: Long Haichen , Li Yangyang , Wang Huijuan , Guo Bingxuan , Song Shuyan , Zhe Xiangyi , Li Hongtao , Li Dongmei , Shao Renfu , Pan Zemin
Published: January 2023

Background

Cervical cancer is currently estimated to be the fourth most common cancer among women worldwide and the leading cause of cancer-related deaths in some of the world’s poorest countries. C/EBPβ has tumor suppressor effects because it is necessary for oncogene-induced senescence. However, C/EBPβ also has an oncogenic role. The specific role of C/EBPβ in cervical cancer as a tumor suppressor or oncoprotein is unclear.

Objective

To explore the role of the C/EBPβ protein in cervical tumorigenesis and progression.

Methods

Quantitative RT-PCR was used to analyze C/EBPβ (15 cervical cancer tissue samples and 15 corresponding normal cervical tissue samples), miR-661, and MTA1 mRNA expression in clinical samples (10 cervical cancer tissue samples and 10 corresponding normal cervical tissue samples). Immunohistochemistry was used to analyze C/EBPβ (381 clinical samples), Ki67 (80 clinical samples) and PCNA ( 60 clinical samples) protein expression. MALDI-TOF MassARRAY was used to analyze C/EBPβ gene methylation (13 cervical cancer tissues and 13 corresponding normal cervical tissues). Cell proliferation was analyzed by CCK-8 in cervical cancer cell lines. Western blotting and immunohistochemistry were performed to detect C/EBPβ protein expression levels, and mRNA expression was analyzed by quantitative RT-PCR analysis. Flow cytometry was performed to measure cell cycle distribution and cell apoptosis. Colony formation, Transwell, cell invasion, and wound healing assays were performed to detect cell migration and invasion.

Results

C/EBPβ protein expression was significantly reduced in cervical cancer tissues compared with cervicitis tissues (P < 0.01). Ki67 protein and PCNA protein expression levels were significantly higher in cervical cancer tissues compared with cervicitis tissues. The rate of C/EBPβ gene promoter methylation of CpG12, 13, 14 and CpG19 in cervical cancer tissues was significantly increased compared with normal cervical tissue (P < 0.05). In addition, C/EBPβ was overexpressed in cervical cancer cells and this overexpression inhibited cell proliferation, migration, invasion, arrested cells in S phase, and promoted apoptosis.

Conclusions

We have demonstrated that C/EBPβ decreased in cervical cancer tissues and overexpression of the C/EBPβ gene in cervical cancer cells could inhibit proliferation, invasion and migration.
Intersection between health, health literacy and local government: a mixed methods approach to identifying ways to better connect people to place-based primary health care in Western Australia
Authors: Millar Lynne , Bhoyroo Ranila , Molina Yesid Pineda , Watts Jessica , Geagea Antoinette , Murphy Jennifer , Pollard Christina M
Published: January 2023

Background

The aim of this year-long mixed methods research was to examine the intersection between health, health literacy and local government to identify ways to better connect people to place-based primary health care (PHC).

Methods

Four local government areas located within the Perth metropolitan geographic area provided the setting for the current research. Researchers were co-located into the four local governments over a 10-month period to engage with community stakeholders and services. Two methodologies were used to achieve the objective: eight group model building (GMB) workshops were conducted withN = 148 participants to create causal loop diagrams of the barriers and enablers to people being healthy and well in each of the LGAs and develop potential action ideas from these. Surveys were used to collect health service use and health literacy, as measured using a validated Health Literacy Questionnaire (HLQ), across the four LGAs (N = 409, approximately 100 respondents/area).

Results

The causal loop diagram themes common across LGAs included: (1) mental health; (2) access to services; (3) health system capacity; (4) economics; and (5) physical wellbeing. Health literacy was relatively high for all nine domains of the HLQ. In the five domains rated from one to four the lowest score was 2.8 for ‘appraisal of information’ and the highest was 3.2 for ‘feeling understood and supported by healthcare providers’. In the four domains rated from one to five; the lowest score was 3.7 for ‘navigating the healthcare system’ and the highest was 4.1 for ‘understand health information well enough to know what to do’. 

Prioritised action ideas recommended increases in practitioners to meet local needs and training General Practitioners and other health staff in culturally sensitive and trauma informed health care. The survey findings and field notes from the GMB were used to construct personas embodied in vignettes highlighting general themes identified in the workshops including those relevant to local areas.

Conclusions

There are many possibilities for health care and local governments to work together to bring services to community members disengaged from the health system. Bringing together people from diverse backgrounds and organisations created synergies that resulted in novel and feasible potential strategies to improve community health.
A recombinant capripoxvirus expressing the F protein of peste des petits ruminants virus and the P12A3C of foot-and-mouth disease virus
Authors: Li Jidong , Wang Jianlin , Guo Yanan , Gong Zhenxing , Cai Xuepeng
Published: January 2023

Background

Peste des petits ruminants (PPR), foot-and-mouth disease (FMD) and sheep pox and goat pox are three important infectious diseases that infect goats, sheep and other small ruminants. It is well-known that the prevention of three diseases rely mainly on their individual vaccines. However, the vaccines have a variety of different disadvantages, such as short duration of immunity, increasing the number of vaccinations, and poor thermal stability. The purpose of this study is to construct a recombinant goat pox virus (rGPV) capable of expressing the F gene of PPRV and the P12A3C gene of FMDV as a live vector vaccine.

Results

The IRES, FMDV P12A3C and PPRV F genes into the multi-cloning site of the universal transfer plasmid pTKfpgigp to construct a recombinant transfer plasmid pTKfpgigpFiP12A3C, and transfected GPV-infected lamb testis (LT) cells with liposomes and produced by homologous recombination Recombinant GPV (rGPV/PPRVF-FMDVP12A3C, rGPV). The rGPV was screened and purified by green florescence protein (GFP) and xanthine-guanine-phosphoribosyltransferase gene (gpt) of Escherichia coli as selective markers, and the expression of rGPV in LT cells was detected by RT-PCR and immunofluorescence techniques. The results showed that the virus strain rGPV/PPRVF-FMDVP12A3C containing FMDV P12A3C and PPRV F genes was obtained. The exogenous genes FMDV P12A3C and PPRV F contained in rGPV were normally transcribed and translated in LT cells, and the expression products could specifically react with PPRV and FMDV antiserum. Then, the rGPV was intradermally inoculated with goats, the animal experiments showed that rGPV/PPRVF-FMDVP12A3C could induce high levels of specific antibodies against GPV, PPRV and FMDV.

Conclusions

The constructed rGPV induced high levels of specific antibodies against GPV, PPRV and FMDV. The study provides a reference for “ one vaccine with multiple uses “ of GPV live vector vaccine.
A PK/PD model for the evaluation of clinical rifaximin dosage for the treatment of dairy cow mastitis induced by Escherichia coli
Authors: Wang Honglei , Chen Chen , Liu Chunshuang , Chen Xiaojie , Zhang Jingju , Wang Yufeng , Han Mingyue , Liu Yiming , Li Xiubo
Published: January 2023

Escherichia coli (E. coli) is an opportunistic pathogen that can cause clinical mastitis in dairy cows worldwide. Mastitis produces severe symptoms in dairy cows, such as udder inflammation, the production of harmful substances, reduced milk production, and altered milk quality. Intramammary injections of rifaximin have a beneficial effect on dairy cow mastitis, especially for mastitis caused by E. coli. However, we do not know whether the currently accepted clinical administration scheme is reasonable. Therefore, the purpose of this experiment was to evaluate the clinical dosing regimen for curing mastitis induced by E. coli. In this study, the pharmacokinetics of four single dose groups (50, 100, 200, and 400 µg/gland) were studied in CD-1 lactating mice, and the main pharmacokinetic parameters were obtained by non-compartment and two-compartment model of Phoenix 8.1 software. A total of 5,000 colony-forming units (CFU) of E. coli ATCC25922 were injected into the mammary glands of mice under anatomic microscope guidance. After 12 h of growth in vivo, the mouse mastitis model was successfully developed. In pharmacodynamics experiment, 12 different dosing regimens (doses ranged from 25 to 800 µg/gland and two dosing intervals of 12 and 24 h) were used to study the therapeutic potential of rifaximin for mastitis. The PK/PD model was established by integrating pharmacokinetics and pharmacodynamics using the inhibitory sigmoid Emax model. The optimal antibacterial effect was 2log10CFU/gland reduction of bacterial colony counts in vivo, when the magnitude of AUC24/MIC exceeded 57.80 h. A total of 57.80 h of AUC24/MIC was defined as a target value in the Monte Carlo simulation. The clinically recommended dosage regimen of 100 mg/gland every 12 h in a day achieved a 91.08% cure rate for the treatment of bovine mastitis caused by E. coli infection.
Relationship of liver fat content with systemic metabolism and chronic complications in patients with type 2 diabetes mellitus
Authors: Ren Weiwei , Feng Yunlu , Feng Youzhen , Li Jiaying , Zhang Chuangbiao , Feng Lie , Cui Lijuan , Ran Jianmin
Published: January 2023

Objective

This study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients.

Methods

Eighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared.

Results

BMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05).

Conclusion

LFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.
Ovulation induction drug and ovarian cancer: an updated systematic review and meta-analysis
Authors: Yu Liang , Sun Jiafan , Wang Qiqin , Yu Wennian , Wang Anqi , Zhu Shu , Xu Wei , Wang Xiuli
Published: January 2023

Objective

To explore the association between ovulation induction drugs and ovarian cancer.

Design

Systematic review and meta-analysis.

Setting

Not applicable.

Patient(s)

Women without ovarian cancer who ever or never underwent ovarian induction.

Intervention(s)

An extensive electronic search of the following databases was performed: PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library and CNKI, from inception until January 2022. A total of 34 studies fulfilled our inclusion criteria and were included in the final meta-analysis. The odds ratio (OR) and random-effects model were used to estimate the pooled effects. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Funnel plots and Egger tests were used to assess publication bias.

Main outcomes

New diagnosed borderline ovarian tumor (BOT) and invasive ovarian cancer (IOC) between ovulation induction (OI) group and control (CT) group considering fertility outcome, OI cycles and specific OI drugs.

Results

Primarily, there was no significant difference in the incidence of IOC and BOT between the OI and CT groups. Secondly, OI treatment did not increase the risk of IOC and BOT in the multiparous women, nor did it increase the risk of IOC in the nulliparous women. However, the risk of BOT appeared to be higher in nulliparous women treated with OI treatment. Thirdly, among women exposed to OI, the risk of IOC and BOT was higher in nulliparous women than in multiparous women. Fourthly, the risk of IOC did not increase with increasing OI cycles. Lastly, exposure to specific OI drugs also did not contribute to the risk of IOC and BOT.

Conclusion

Overall, OI treatment did not increase the risk of IOC and BOT in most women, regardless of OI drug type and OI cycle. However, nulliparous women treated with OI showed a higher risk of ovarian cancer, necessitating their rigorous monitoring and ongoing follow-up.
Epigenetic dysregulation-mediated COL12A1 upregulation predicts worse outcome in intrahepatic cholangiocarcinoma patients
Authors: Tang Zengwei , Yang Yuan , Zhang Qi , Liang Tingbo
Published: January 2023

Background

Collagen type XII alpha 1 chain (COL12A1) is associated with human cancer progression. Nevertheless, the expression pattern and the function of COL12A1 in intrahepatic cholangiocarcinoma (iCCA) remain unknown. The present study was performed to assess the role of COL12A1 in iCCA.

Results

A total of 1669 genes, differentially expressed between iCCA and nontumor liver tissue samples, were identified as potential tumor-specific biomarkers for iCCA patients. Of these, COL12A1 was significantly upregulated in clinical iCCA tissue samples and correlated with epithelial–mesenchymal transition gene set enrichment score and advanced tumor stage in clinical iCCA. COL12A1-high expression was associated with the poor prognoses of iCCA patients (n = 421) from four independent cohorts. Promoter hypermethylation-induced downregulation of miR-424-5p resulted in COL12A1 upregulation in clinical iCCA. Experimental knockout of COL12A1 inhibited the proliferation, invasiveness and growth of iCCA cells. MiR-424-5p had a therapeutic potential in iCCA via directly targeting COL12A1.

Conclusions

Promoter hypermethylation-induced miR-424-5p downregulation contributes to COL12A1 upregulation in iCCA. COL12A1 is a promising druggable target for epigenetic therapy of iCCA.

Graphical Abstract
Optimization of the radiation dosimetry protocol in Lutetium-177-PSMA therapy: toward clinical implementation
Authors: Peters Steffie M. B. , Mink Maaike C. T. , Privé Bastiaan M. , de Bakker Maarten , de Lange Frank , Muselaers Constantijn H. J. , Mehra Niven , Witjes J. Alfred , Gotthardt Martin , Nagarajah James , Konijnenberg Mark W.
Published: January 2023

Background

Dosimetry in [177Lu]Lu-PSMA therapy is a valuable tool to assess treatment efficacy and toxicity. This study aims to develop a clinically implementable protocol to determine the absorbed dose in organs and tumor lesions after [177Lu]Lu-PSMA-617 therapy, by reducing the imaging time points and utilizing population-based kinetics with a single scan, with evaluation of its influence on the uncertainty in absorbed dose.

Methods

Ten patients with metastatic hormone-sensitive prostate cancer received two cycles of [177Lu]Lu-PSMA-617. Post-treatment imaging was performed at 1 h, 24 h, 48 h, 72 h and 168 h, consisting of three-bed positions SPECT/CT and a whole-body planar scan. Five-time point SPECT dosimetry was performed for lesions and organs with physiological uptake (kidneys, liver and salivary glands) and used as the reference standard. Absorbed dose values for various simplified protocols were compared to the reference standard.

Results

Accurate lesion dosimetry is possible using one-time point SPECT imaging at 168 h, with an increase in uncertainty (20% vs. 14% for the reference standard). By including a second time point, uncertainty was comparable to the reference standard (13%). Organ dosimetry can be performed using a single SPECT at 24 h or 48 h. Dosimetry based on planar scans did not provide accurate dose estimations.

Conclusion

Accurate lesion dosimetry in [177Lu]Lu-PSMA therapy can be performed using a one- or two-time point protocol, making dosimetry assessments more suitable for routine clinical implementation, although dosimetry based om multiple time points is more accurate.

Clinical trial registration This study was approved by the Medical Review Ethics Committee Region Arnhem-Nijmegen on January 23, 2018 and was registered on clinicaltrials.gov (NCT03828838).
Brain nuclear receptors and cardiovascular function
Authors: Wang Mengjie , Yang Yongjie , Xu Yong
Published: January 2023

Brain–heart interaction has raised up increasing attentions. Nuclear receptors (NRs) are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis, etc. In this review, we will elaborate recent findings that have established the physiological relevance of brain NRs in the context of cardiovascular function. In addition, we will discuss the currently available evidence regarding the distinct neuronal populations that respond to brain NRs in the cardiovascular control. These findings suggest connections between cardiac control and brain dynamics through NR signaling, which may lead to novel tools for the treatment of pathological changes in the CVDs.
A novel machine learning model based on ubiquitin-related gene pairs and clinical features to predict prognosis and treatment effect in colon adenocarcinoma
Authors: Liang Liping , Liu Le , Mai Shijie , Chen Ye
Published: January 2023

Background

Ubiquitin and ubiquitin-like (UB/UBL) conjugations are essential post-translational modifications that contribute to cancer onset and advancement. In colon adenocarcinoma (COAD), nonetheless, the biological role, as well as the clinical value of ubiquitin-related genes (URGs), is unclear. The current study sought to design and verify a ubiquitin-related gene pairs (URGPs)-related prognostic signature for predicting COAD prognoses.

Methods

Using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression, URGP's predictive signature was discovered. Signatures differentiated high-risk and low-risk patients. ROC and Kaplan–Meier assessed URGPs' signature. Gene set enrichment analysis (GSEA) examined biological nomogram enrichment. Chemotherapy and tumor immune microenvironment were also studied.

Results

The predictive signature used six URGPs. High-risk patients had a worse prognosis than low-risk patients, according to Kaplan–Meier. After adjusting for other clinical characteristics, the URGPs signature could reliably predict COAD patients. In the low-risk group, we found higher amounts of invading CD4 memory-activated T cells, follicular helper T cells, macrophages, and resting dendritic cells. Moreover, low-risk group had higher immune checkpoint-related gene expression and chemosensitivity.

Conclusion

Our research developed a nomogram and a URGPs prognostic signature to predict COAD prognosis, which may aid in patient risk stratification and offer an effective evaluation method of individualized treatment in clinical settings.
CircFBXW7 in patients with T-cell ALL: depletion sustains MYC and NOTCH activation and leukemia cell viability
Authors: Buratin Alessia , Borin Cristina , Tretti Parenzan Caterina , Dal Molin Anna , Orsi Silvia , Binatti Andrea , Simon Katharina , Paganin Maddalena , Serafin Valentina , Gaffo Enrico , te Kronnie Geertruij , Van Vlierberghe Pieter , Bresolin Silvia , Bortoluzzi Stefania
Published: January 2023

Circular RNAs (circRNAs) are emerging as new players in leukemogenic mechanisms. In patients with T-cell Acute Lymphoblastic Leukemia (T-ALL), the recent report of a remarkable dysregulation of circRNAs incited further functional investigation. Here we focus on circFBXW7, highly expressed in T-cells, with a notably high abundance of the circular compared to linear transcript of FBXW7. Two T-ALL patient cohorts profiled with RNA-seq were analyzed in comparison with five populations of developing thymocytes as normal counterpart, quantifying circRNA and gene expression. CircFBXW7 expression was very heterogeneous in T-ALL patients allowing their stratification in two groups with low and high expression of this circRNA, not correlated with FBXW7 mutation status and T-ALL molecular subgroups. With a loss-of-function study in T-ALL in vitro, we demonstrate that circFBXW7 depletion increases leukemic cell viability and proliferation. Microarray profiling highlighted the effect of the circFBXW7 silencing on gene expression, with activation of pro-proliferative pathways, supporting a tumor suppressor role of circFBXW7 in T-ALL. Further, MYC and intracellular NOTCH1 protein levels, as well as expression of MYC target and NOTCH signaling genes were elevated after circFBXW7 depletion, suggesting an inhibitory role of circFBXW7 in these oncogenic axes. Plus, low circFBXW7 levels were associated with a particular gene expression profile in T-ALL patients, which was remarkably mirrored by the effects of circFBXW7 loss-of-function in vitro. CircFBXW7 depletion notably emerges as a new factor enhancing a proliferative phenotype and the activation of the MYC signaling pathway, key players in this aggressive malignancy.
Disparities in access to eating disorders treatment for publicly-insured youth and youth of color: a retrospective cohort study
Authors: Moreno Ruby , Buckelew Sara M. , Accurso Erin C. , Raymond-Flesch Marissa
Published: January 2023

Background

Eating disorders are associated with substantial morbidity and mortality that can be minimized by timely access to evidence-based treatment. However, disparate access to eating disorders treatment may contribute to significant health disparities amongst marginalized groups. This study examined the association between insurance type (public vs. private) and receipt of recommended mental health treatment in a sample of racially/ethnically diverse youth who presented to an adolescent medicine clinic with malnutrition secondary to disordered eating.

Methods

A retrospective chart review was conducted for youth ages 11–25 years (N = 1060) who presented to an urban adolescent medicine specialty program between June 1, 2012 and December 31, 2019 for malnutrition secondary to disordered eating. Bivariate and logistic regression analyses examined the association between insurance type (public vs. private) and other demographic/clinical factors on receipt of recommended treatment within six months of the initial evaluation.

Results

Patients with public insurance were one third as likely to receive recommended treatment as patients with private insurance (AOR = 3.23; 95% CI = 1.99, 4.52), after adjusting for demographic and clinical factors. Latinx (AOR = 0.49; 95% CI = 0.31, 0.77) and Asian (AOR = 0.55; 95% CI = 0.32, 0.94) patients were half as likely to receive recommended treatment as White patients.

Conclusions

Access to evidence-based mental health treatment is a necessary first step towards health equity for individuals with eating disorders. Additional work is needed to dismantle systemic inequities that contribute to disparities in care for youth of color and those with public insurance.
Educational L2 constructs and diagnostic measurement
Authors: Yumsek Meltem
Published: January 2023

Various stakeholders, such as policymakers and educators, require diagnostic feedback and actionable test results. One particular context in which fine-grained test results are of utmost importance is English language proficiency (ELP) assessments as they are used for critical decisions for students. Diagnostic classification models (DCMs) afford finer levels of feedback to improve learning outcomes. This study is part of a research project which implemented DCMs to the reading domain of a K–12 ELP assessment for grades 6–8 to evaluate its feasibility and utility. The research project is U.S.-based. However, the investigation is of relevance to the language testing community broadly. The paper discusses how to address second language reading construct within DCMs. Specifically, it details the identification of attributes underlying the construct and the development and selection of alternative Q-matrices.
Prediction of hamstring tendon autograft diameter using preoperative measurements with different cut‐offs between genders
Authors: Movahedinia Mohammad , Movahedinia Sajjadeh , Hosseini Seyedreza , Motevallizadeh Ali , Salehi Bentolhoda , Shekarchi Babak , Shahrezaee Mostafa
Published: January 2023

Purpose

Studies have suggested some predictors for hamstring tendon (HT) autograft diameter based on anthropometric factors and preoperative magnetic resonance imaging (MRI) with variable results. Some authors have attributed the variability to gender differences. This prospective cohort reports the sensitivity and specificity of anthropometric and MRI predictors in males and females separately to determine the difference.

Methods

Forty‐two eligible patients who underwent anterior cruciate ligament reconstruction (ACLR) and MRI in our center were included. ACLR was performed by the senior surgeon using a 4‐stranded HT autograft for all patients. A blinded musculoskeletal radiologist measured the cross‐sectional area (CSA) of gracilis and semitendinosus tendons using the free‐hand region of interest tool for all patients. An orthopaedic resident (PGY4) collected anthropometric factors and measured intraoperative autograft diameter.

Results

Mean intraoperative autograft diameter was 8.0 mm. Females had a significantly lower autograft diameter (7.4 vs. 8.2, P < 0.001), smaller gracilis (6.9 vs. 7.9, P = 0.003) and semitendinosus CSA (11.5 vs. 12.8, P = 0.014) compared to males. ROC curve analysis resulted different cut‐off values with high sensitivity and specificity for semitendinosus and combined CSA regarding gender.

Conclusion

Based on the results of this study, CSA of either isolated or combined HTs on preoperative axial MRI, height, and weight are the strongest predictors of intraoperative autograft diameter. It is suggested to consider different cut‐offs for males and females to have a better clinical guide for surgeons.

Level of evidence

Level II.
Advanced Image Segmentation and Modeling – A Review of the 2021–2022 Thematic Series
Authors: Ravi Prashanth
Published: January 2023

Medical 3D printing is a form of manufacturing that benefits patient care, particularly when the 3D printed part is patient-specific and either enables or facilitates an intervention for a specific condition. Most of the patient-specific medical 3D printing begins with volume based medical images of the patient. Several digital manipulations are typically performed to prescribe a final anatomic representation that is then 3D printed. Among these are image segmentation where a volume of interest such as an organ or a set of tissues is digitally extracted from the volumetric imaging data. Image segmentation requires medical expertise, training, software, and effort. The theme of image segmentation has a broad intersection with medical 3D printing. The purpose of this editorial is to highlight different points of that intersection in a recent thematic series within 3D Printing in Medicine.
Expression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer
Authors: Farooq Muzamil , Bhat Gh. Rasool , Besina Syed , Thakur Natasha , Zahoor Sheikh , Rather Rafiq A. , Mushtaq Ifra , Dar Sadaf , Rah Bilal , Bhat Ajaz A. , Macha Muzafar A. , Afroze Dil
Published: January 2023

Hypoxic zones exist in solid tumors, where oxygen levels are significantly lower than in normal tissues. Hypoxia makes chemo-radiation therapeutics less effective and renders the metastatic potential more favorable. Emerging research has found that the transcriptional expression of hypoxia-inducible factor-1alpha (HIF-1α) promotes the transcription of vascular endothelial growth factor A (VEGF-A) and Hexokinase-I (HK-I), which are associated to cellular growth, angiogenesis, and metastatic invasion in many malignancies. However, it is still unclear whether VEGFA and HK-I expression has any influence on survival based on the intrinsic subtypes of breast cancer. Their prognostic significance remains a debatable topic. In the present study, quantitative Real-time polymerase chain reaction (qRT-PCR) was employed to check the relative expression of HIF-1α, VEGF-A and HK-I. The hazard ratios (HR) of breast cancer-specific and overall mortality were calculated using Cox proportional hazards model, which were adjusted for demographic, clinicopathological, and associated molecular variables, as well as the diagnosis year. The relative mRNA expression levels of HIF-1α (p = 0.0010) and VEGFA (p = 0.0119) were significantly higher in tumor tissues. The expression of both HIF-1α (p = 0.0111) and VEGFA (p = 0.0078) was higher in the TNBC group of breast cancers, while HK-I (p = 0.0106) was higher in ER/PR-positive, HER2-negative group. HIF-1α and HK-I overexpression were associated with a higher likelihood of survival, while overexpression of VEGFA was associated with a low survival rate, although it was not statistically significant.
Patient participation in defining best-practice rheumatology service provision in Aotearoa New Zealand: a qualitative study with service consumers
Authors: Ngan Kee Rachel , Milne Valerie , Dalbeth Nicola , Grainger Rebecca
Published: January 2023

Background

Aotearoa New Zealand (AoNZ) has no agreed models for rheumatology service provision in government-funded health care. We aimed to describe what people with inflammatory rheumatic diseases who have used rheumatology services view as being important in those services, and map these views to previously collated statements describing best practice components of rheumatology services from international recommendations. If these statements did not capture all service aspects that people with inflammatory rheumatic diseases considered important, we aimed to co-create new statements with our patient-participants.

Methods

We conducted one focus group and an interview with people with inflammatory rheumatic disease who had used a government-funded rheumatology service in the previous 5 years (patient-participants) and analysed data using thematic analysis. The research team mapped subthemes to previously collated best practice recommendations that had been included in a Delphi consensus exercise with rheumatologists in AoNZ and proposed new statements, based on patient-participant data. Patient-participant feedback on thematic analysis and the new statements led to a refining of statements. A patient-partner in the research team informed research design and data analysis.

Results

Patient-participants viewed it as highly valuable for rheumatology services to respect and value their experiences as people and patients, and those of their whānau (Māori word for family). They expected rheumatology services to provide the right care, at the right time. Many of the subthemes mapped to the best-practice statements. However, three new principles and three new statements were developed and refined by patient-participants. The three principles addressed valuing individuals, and their whānau (family) and their experiences, and providing a patient-focused health system that supports patient participation in decision-making and self-management, and patient education. New statements related to having a specific rheumatologist and other staff for comprehensive care, having adequate nurse staffing, and active provision of outside services and support.

Conclusion

It was important to patients that rheumatology services demonstrated that patients and their whānau (family) were valued. The inclusion of people with rheumatic diseases who are users of rheumatology services in service development can provide valuable insights to inform how services should be delivered.
Management of ST-segment elevation myocardial infarction in comparison to European society of cardiology guidelines in Alexandria University Hospitals, Egypt
Authors: Kamal Amr , Zaki Amr , Abdelaaty Ahmed , Madkour Moustafa
Published: January 2023

Background

For patients with ST-elevation myocardial infarction (STEMI), early reperfusion with primary percutaneous coronary intervention (PPCI) or thrombolytic treatment is essential to prevent major adverse cardiac events. The aim of the study is to compare the current status of managing STEMI patients at **** with European Society of Cardiology guidelines recommendations. Prospective cohort of all patients presenting with ST-elevation myocardial infarction (STEMI) between March 2020 and February 2021 in Alexandria University hospitals. Reporting patterns, causes of delay, and reperfusion status for all STEMI patients were noted. MACE: (Mortality, Re-infarction, Stroke, or Heart failure) was reported and compared among different management strategies.

Results

The study was conducted over one year on 436 patients, 280 (64.2%) of them underwent PPCI, 32 (7.3%) received thrombolysis, and 124 (28.5%) had a conservative strategy. Patients’ mean age was 55.2 years, 72.2% were smokers and 80.9% were men. Family history was positive in 14.2% of patients, 33.5% had diabetes, 7.3% had renal impairment, and 41.5% had hypertension. The median pre-hospital waiting time was 360 min; the mean pre-hospital waiting time was 629.0 ± 796.7 min. The median Emergency Room waiting time was 48.24 ± 89.30 min. The median time from CCU admission to wire crossing was 40.0 min with a mean value 53.86 ± 49.0 min. The mean ischemia duration was 408 min, while the total ischemic time was 372 min. All patients who presented within 12 h received reperfusion therapy either a PPCI or thrombolysis at a rate of 71.5%, with 35.0% of those patients achieving prompt reperfusion in accordance with ESC guidelines. The PPCI group mortality rate was 2.9%, in comparison to 12.9% in the conservative group, which was statistically significant (P < 0.001). Overall in-hospital mortality was 5.5%, and total MACE was 27.3%. A statistically significant difference was observed between the three management groups as regards MACE rate, being 15%, 28.1%, and 54.8% in PPCI, thrombolysis, and conservative groups, respectively.

Conclusions

Despite financial and technical constraints, appropriate, timely reperfusion was near to achieving the ESC guidelines for the management of STEMI. The most common reperfusion strategy was PPCI, with an in-hospital death rate of less than 5% in the PPCI group. There was a concern about the increase in the total ischemia time due to some financial and technical constraints.
The interplay between left ventricular diastolic and right ventricular dysfunction: challenges in the interpretation of critical care echocardiography studies
Authors: La Via Luigi , Merola Federica , Schembari Giovanni , Liotta Calogero , Sanfilippo Filippo
Published: January 2023

Background

Sepsis is a leading cause of death and it is characterized not only by profound vasoplegia but also by myocardial dysfunction. Critical care echocardiography is the preferred modality for the initial assessment of the cause of shock. Moreover, it can be extremely helpful in the identification of progressing myocardial dysfunction during the course of sepsis, also known as septic cardiomyopathy.

Main body

One of the issues in the identification of septic cardiomyopathy is that it can be manifest with different clinical phenotypes, from overt biventricular dysfunction to isolated left ventricular (LV) systolic and/or diastolic dysfunction, from right ventricular (RV) systolic dysfunction to RV failure and dilatation. However, the commonly used echocardiography parameters for the assessment of LV and/or RV function are not always entirely reliable. Indeed, these are influenced by variable preload and afterload conditions imposed by critical illness such as fluid shifts, sedation level and mechanical ventilation with positive pressure.

Conclusions

Strain echocardiography is a promising tool for the early identification of myocardial dysfunction in the context of sepsis. Studies reporting data on strain echocardiography should be particularly detailed in order to increase the reproducibility of results and to favor comparison with future studies.