bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of patient-related factors on hospitalization service satisfaction and recommendation intention of medical institutions in Korea
Authors: Shin Jeong Woo , Choi Bo Ram
Published: June 2023

Objective

This study examined the factors that influence the 'Overall Satisfaction' and 'Intention to Recommend' of medical institutions used using the Korea Medical Service Experience Survey (2019–2021).

Data sources

This study used the data of Medical Service Experience Survey in Korea. The data collected for data analysis were from 2019 to 2021 (Medical service period: 2018.07.01. ~ 2021.06.30).

Study design

The 2019 Medical Service Experience Survey was conducted from July 8 to September 20, 2019, and a total of 12,507 people (Medical service period: 2018.07.01. ~ 2019.06.30) were collected. The 2020 survey was conducted from July 13 to October 9, 2020, and a total of 12,133 people (Medical service period: 2019.07.01 ~ 2020.06.30.) were collected. The 2021 survey was conducted from July 19 to September 17, 2021), and a total of 13,547 people were collected (Medical service period: 2020.07.01. ~ 2021.06.30). Overall satisfaction and recommendation intentions for medical institutions consist of a Likert 5-point scale. At this time, the Top-box rating model used in the United States was applied.

Data collections/extraction methods

In this study, only those who used inpatient services (15 years of age or older) were included because they spent a long time in a medical institution and had an intensive experience, and a total of 1,105 subjects were included in the analysis.

Principal findings

Self-rated health and the type of bed influenced overall satisfaction with medical institutions. In addition, the type of economic activity, living area, self-rated health, the type of bed, and the type of nursing service affected the intention to recommend. And it was confirmed that overall satisfaction with medical institutions and intention to recommend them were higher in the 2021 survey than in 2019.

Conclusions

These results suggest that government policy on resources and systems is important. Through the case of Korea, it was found that the policy of reducing multi-person beds and expansion of integrated nursing service had a significant impact on patients' experience of using medical institutions and improving the quality of care.
Exploring an immune cells-related molecule in STEMI by bioinformatics analysis
Authors: Zhang Min , Li Jiaxing , Hua Cuncun , Niu Jiayin , Liu Pengfei , Zhong Guangzhen
Published: June 2023

Background

ST-elevated myocardial infarction (STEMI) is the leading cause of mortality worldwide. The mortality rate of heart attacks has decreased due to various preventive factors and the development of early diagnostic resuscitation measures, but the long-term prognosis remains poor. The present study aimed to identify novel serum biomarkers in STEMI patients and explored a possible new mechanism of STEMI from an immune molecular angle with bioinformatics analysis.

Methods

Gene expression profiles were obtained from Gene Expression Omnibus (GEO) database. Differential gene analysis, machine learning algorithms, gene set enrichment analysis, and immune cell infiltration analysis were conducted using R software.

Results

We identified 146 DEGs (differentially expressed genes) in the integrated dataset between the STEMI and CAD (coronary artery disease) groups. Immune infiltration analysis indicated that eleven cell types were differentially infiltrated. Through correlation analysis, we further screened 25 DEGs that showed a high correlation with monocytes and neutrophils. Afterwards, five genes consistently selected by all three machine learning algorithms were considered candidate genes. Finally, we identified a hub gene (ADM) as a biomarker of STEMI. AUC curves showed that ADM had more than 80% high accuracy in all datasets.

Conclusions

In this study, we explored a potentially new mechanism of STEMI from an immune molecular perspective, which might provide insights into the pathogenesis of STEMI. ADM positively correlated with monocytes and neutrophils, suggesting its potential role in the immune response during STEMI. Additionally, we validated the diagnostic performance of ADM in two external datasets, which could help to develop new diagnostic tools or therapeutic strategies.
Clinical and molecular features of NDM-producing Acinetobacter baumannii in a multicenter study in Israel
Authors: Adler Amos , Ghosh Hiren , Gross Andrea , Rechavi Amit , Lasnoy Michal , Assous Marc V. , Geffen Yuval , Darawsha Basel , Wiener-Well Yonit , Alony Anat , Grundmann Hajo , Reuter Sandra
Published: June 2023

Background

NDM-producing Acinetobacter baumannii (NDMAb) were reported sporadically worldwide but little is known about the transmission, epidemiology and clinical features of NDMAb-infected patients. The goals of this study were to characterize (1) the epidemiology and clinical features of NDMAb–infected patients; (2) the microbiological and molecular features of NDMAb isolates and (3) the transmission networks of NDMAb within healthcare facilities.

Methods

The study was conducted at the Tel-Aviv Sourasky, Rambam and Sha’are-Zedek Medical centers (TASMC, RMC and SZMC, respectively) in Israel. All cases detected between January 2018 and July 2019 were included. Phylogenetic analysis was based on core genome SNP distances. Clonal transmission was defined according to molecular (≤ 5 SNP) and epidemiological criteria (overlapping hospital stay). NDMAb cases were compared at a ratio of 1:2 with non-NDM carbapenem-resistant A. baumannii (CRAb) cases.

Results

The study included 54 NDMAb-positive out of 857 CRAb patients, including 6/179 (3.3%) in TASMC, 18/441 (4.0%) in SZMC and 30/237 (12.6%) in RMC. Patients infected by NDMAb had similar clinical features and risk factors as patients with non-NDM CRAb. The length-of-stay was higher in NDMAb cases (48.5 days vs. 36 days, respectively, p = 0.097) and the in-hospital mortality was similarly high in both groups. Most isolates (41/54, 76%) were first detected from surveillance culture. The majority of isolates harbored the blaNDM−2 gene allele (n = 33), followed by the blaNDM−1 (n = 20) allele and the blaNDM−4 allele (n = 1). The majority of isolates were related within the ST level to other isolates in SZMC and RMC: 17/18 and 27/30 isolates, respectfully. The common ST’s were the blaNDM−1 harboring ST-2 (n = 3) and ST-107 (n = 8) in SZMC and the blaNDM−2 harboring ST-103 in SZMC (n = 6) and in RMC (n = 27). All blaNDM alleles were located within a conserved mobile genetic environment flanked by the ISAb125 and IS91 family transposon. Clonal transmission was identified in most hospital-acquired cases in RMC and SZMC.

Conclusion

NDMAb constitutes a minor part of CRAb cases and are clinically similar to non-NDM CRAb. Transmission of NDMAb occurs mostly by clonal spread.
Epigenetic modification of m6A regulator proteins in cancer
Authors: Wang Yumin , Wang Yan , Patel Harsh , Chen Jichao , Wang Jinhua , Chen Zhe-Sheng , Wang Hongquan
Published: June 2023

Divergent N6-methyladenosine (m6A) modifications are dynamic and reversible posttranscriptional RNA modifications that are mediated by m6A regulators or m6A RNA methylation regulators, i.e., methyltransferases (“writers”), demethylases (“erasers”), and m6A-binding proteins (“readers”). Aberrant m6A modifications are associated with cancer occurrence, development, progression, and prognosis. Numerous studies have established that aberrant m6A regulators function as either tumor suppressors or oncogenes in multiple tumor types. However, the functions and mechanisms of m6A regulators in cancer remain largely elusive and should be explored. Emerging studies suggest that m6A regulators can be modulated by epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, and lactylation or via noncoding RNA action, in cancer. This review summarizes the current roles of m6A regulators in cancer. The roles and mechanisms for epigenetic modification of m6A regulators in cancer genesis are segregated. The review will improve the understanding of the epigenetic regulatory mechanisms of m6A regulators.
Targeting RNA-binding protein HuR to inhibit the progression of renal tubular fibrosis
Authors: Huang Zhimin , Liu Simeng , Tang Anna , Wu Xiaoqing , Aube Jeffrey , Xu Liang , Huang Yufeng
Published: June 2023

Background

Upregulation of an RNA-binding protein HuR has been implicated in glomerular diseases. Herein, we evaluated whether it is involved in renal tubular fibrosis.

Methods

HuR was firstly examined in human kidney biopsy tissue with tubular disease. Second, its expression and the effect of HuR inhibition with KH3 on tubular injury were further assessed in a mouse model induced by a unilateral renal ischemia/reperfusion (IR). KH3 (50 mg kg−1) was given daily via intraperitoneal injection from day 3 to 14 after IR. Last, one of HuR-targeted pathways was examined in cultured proximal tubular cells.

Results

HuR significantly increases at the site of tubular injury both in progressive CKD in patients and in IR-injured kidneys in mice, accompanied by upregulation of HuR targets that are involved in inflammation, profibrotic cytokines, oxidative stress, proliferation, apoptosis, tubular EMT process, matrix remodeling and fibrosis in renal tubulointerstitial fibrosis. KH3 treatment reduces the IR-induced tubular injury and fibrosis, accompanied by the remarkable amelioration in those involved pathways. A panel of mRNA array further revealed that 519 molecules in mouse kidney following IR injury changed their expression and 71.3% of them that are involved in 50 profibrotic pathways, were ameliorated when treated with KH3. In vitro, TGFβ1 induced tubular HuR cytoplasmic translocation and subsequent tubular EMT, which were abrogated by KH3 administration in cultured HK-2 cells.

Conclusions

These results suggest that excessive upregulation of HuR contributes to renal tubulointerstitial fibrosis by dysregulating genes involved in multiple profibrotic pathways and activating the TGFß1/HuR feedback circuit in tubular cells. Inhibition of HuR may have therapeutic potential for renal tubular fibrosis.
Endothelial progenitor cell-derived exosomes promote anti-inflammatory macrophages via SOCS3/JAK2/STAT3 axis and improve the outcome of spinal cord injury
Authors: Yuan Feifei , Peng Wei , Yang Yuying , Xu Jiaqi , Liu Yudong , Xie Yong , Huang Tingmo , Shi Chaoran , Ding Yinghe , Li Chengjun , Qin Tian , Xie Shanshan , Zhu Fengzhang , Lu Hongbin , Huang Jianjun , Hu Jianzhong
Published: June 2023

Background

Macrophage in the spinal cord injury (SCI) area imparts a chronic pro-inflammation effect that challenges the recovery of SCI. Previously, endothelial progenitor cell-produced exosomes (EPC-EXOs) have been noticed to facilitate revascularization and inflammation control after SCI. However, their effects on macrophage polarization remained unclear. This study aimed to investigate the EPC-EXOs' role in macrophage polarization and reveal its underlying mechanism.

Methods

We extracted the macrophages and EPC from the bone marrow suspension of C57BL/L mice by centrifugation. After cell identification, the EPC-EXOs were collected by ultra-high-speed centrifugation and exosome extraction kits and identified by transmission electron microscopy and nanoparticle tracking analysis. Then, macrophages were cultured with EPC-EXOs in different concentrations. We labeled the exosome to confirm its internalization by macrophage and detected the macrophage polarization marker level both in vitro and in vivo. We further estimated EPC-EXOs' protective effects on SCI by mice spinal cord tissue H&E staining and motor behavior evaluation. Finally, we performed RT-qPCR to identify the upregulated miRNA in EPC-EXOs and manipulate its expression to estimate its role in macrophage polarization, SOCS3/JAK2/STAT3 pathway activation, and motor behavior improvement.

Results

We found that EPC-EXOs decreased the macrophages’ pro-inflammatory marker expression and increased their anti-inflammatory marker expression on the 7 and 14 days after SCI. The spinal cord H&E staining results showed that EPC-EXOs raised the tissue-sparing area rate significantly after 28 days of SCI and the motor behavior evaluation indicated an increased BMS score and motor-evoked potential by EPC-EXOs treatment after SCI. The RT-qPCR assay identified that miR-222-3P upregulated in EPC-EXOs and its miRNA-mimic also decreased the pro-inflammatory macrophages and increased the anti-inflammatory macrophages. Additionally, miR-222-3P mimic activated the SOCS3/JAK2/STAT3 pathway, and SOCS3/JAK2/STAT3 pathway inhibition blocked miR-2223P’s effects on macrophage polarization and mouse motor behavior.

Conclusion

Comprehensively, we discovered that EPC-EXOs-derived miR-222-3p affected macrophage polarization via SOCS3/JAK2/STAT3 pathway and promoted mouse functional repair after SCI, which reveals EPC-EXOs’ role in modulation of macrophage phenotype and will provide a novel interventional strategy to induce post-SCI recovery.
Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of Huang–Qi–Gui–Zhi–Wu–Wu decoction against deep vein thrombosis
Authors: Fan Wei , Lan Shuangli , Yang Yunkang , Liang Jie
Published: June 2023

Background

Huangqi Guizhi Wuwu decoction (HQGZWWD) has been used to treat and prevent deep vein thrombosis (DVT) in China. However, its potential mechanisms of action remain unclear. This study aimed to utilize network pharmacology and molecular docking technology to elucidate the molecular mechanisms of action of HQGZWWD in DVT.

Methods

We identified the main chemical components of HQGZWWD by reviewing the literature and using a Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. We used GeneCards and Online Mendelian Inheritance in Man databases to identify the targets of DVT. Herb-disease-gene-target networks using Cytascape 3.8.2 software; a protein–protein interaction (PPI) network was constructed by combining drug and disease targets on the STRING platform. Additionally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking verification of active components and core protein targets was conducted.

Results

A total of 64 potential targets related to DVT were identified in HQGZWWD, with 41 active components; quercetin, kaempferol, and beta-sitosterol were the most effective compounds. The PPI network analysis revealed that AKT1, IL1B, and IL6 were the most abundant proteins with the highest degree. GO analysis indicated that DVT treatment with HQGZWWD could involve the response to inorganic substances, positive regulation of phosphorylation, plasma membrane protein complexes, and signaling receptor regulator activity. KEGG analysis revealed that the signaling pathways included pathways in cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. The molecular docking results indicated that quercetin, kaempferol, and beta-sitosterol exhibited strong binding affinities for AKT1, IL1B, and IL6.

Conclusion

Our study suggests that AKT1, IL1B, and IL6 are promising targets for treating DVT with HQGZWWD. The active components of HQGZWWD likely responsible for its effectiveness against DVT are quercetin, kaempferol, and beta-sitosterol, they may inhibit platelet activation and endothelial cell apoptosis by regulating the PI3K/Akt and MAPK signaling pathways, slowing the progression of DVT.
Efficient production of icariin and baohuoside I from Epimedium Folium flavonoids by fungal α-l-rhamnosidase hydrolysing regioselectively the terminal rhamnose of epimedin C
Authors: Zhang Shanshan , Lu Changning , Cao Shiping , Li Qi , Wu Guangwei , Zhao Linguo
Published: June 2023

Industrial application of icariin and baohuoside I has been hindered by the short supply to a great extent. In this work, a novel GH78 α-l-rhamnosidase AmRha catalyzed the bioconversion of low-value epimedin C in crude Epimedium Folium flavonoids (EFs) to icariin and baohuoside I was developed. Firstly, the high-level expression of AmRha in Komagataella phaffii GS115 attained an enzyme activity of 571.04 U/mL. The purified recombinant AmRha could hydrolyze α-1,2-rhamnoside bond between two rhamnoses (α-Rha(2 → 1)α-Rha) in epimedin C to produce icariin with a molar conversion rate of 92.3%, in vitro. Furtherly, the biotransformation of epimedin C to icariin by the recombinant Komagataella phaffii GS115 cells was also investigated, which elevated the EFs concentration by fivefold. In addition, biotransformation of epimedins A-C and icariin in the raw EFs to baohuoside I was fulfilled by a collaboration of AmRha and β-glucosidase/β-xylosidase Dth3. The results obtained here provide a new insight into the preparation of high-value products icariin and baohuoside I from cheap raw EFs.
Two peptides derivate from Acinetobacter baumannii outer membrane protein K as vaccine candidates: a comprehensive in silico study
Authors: Heidarinia Hana , Tajbakhsh Elahe , Rostamian Mosayeb , Momtaz Hassan
Published: June 2023

Background

The lack of appropriate vaccines is an obstacle to the effective management of A. baumannii infections. Peptide vaccines offer an attractive and promising preventive strategy against A. baumannii.

Objective

In this study, we identified specific T cell epitopes of A. baumannii outer membrane protein K (OMPK) using comprehensive bioinformatics and detailed molecular docking analysis.

Methods

Both class-I and class-II T cell epitopes of A. baumannii OMPK were predicted by three tools namely IEDB, SYFPEITHI, and ProPred. The predicted epitopes were shortlisted based on several analyses including prediction scoring, clustering, exclusion of human similarity, considering immunogenicity and cytokine production, and removal of toxic and/or allergen epitopes. The epitopic peptides with high prediction scores and appropriate properties containing both class-I and class-II T cell epitopes were selected. Two of these class I/II epitopic peptides were chosen for molecular docking studies and assessing their physicochemical properties as vaccine candidates.

Results

The results showed many T-cell epitopes of OMPK that could be evaluated for possible immunogenicity. Two of these epitopes (containing both class-I and II epitopes) had high prediction scores, were predicted by several tools, attached to several HLAs, and had the best docking score. They had different physicochemical properties and were conserved among Acinetobacter species.

Discussion

We identified the A. baumannii OMPK high immunogenic class-I and class-II T cell epitopes and introduced two promising high immunogenic peptides as vaccine candidates. It is recommended to perform in vitro/in vivo investigation of these peptides to determine their true efficacy and efficiency.
A rare primary hepatic neuroendocrine tumour with laparoscopic resection: a case report
Authors: Alghamdi Hanan M.
Published: June 2023

Introduction

Primary hepatic neuroendocrine tumours (PHNETs) are a rare form of hepatic neoplasms, and it is difficult to differentiate them from common hepatic malignancies in routine imaging studies.

Presentation of the case

We describe the case of a 60-year-old Indian male patient with a tentative preoperative diagnosis of hepatocellular carcinoma (HCC). Nevertheless, the definitive post-operative diagnosis was made by Histopathological and immunohistochemical assessment, which revealed a grade II neuroendocrine tumour (NET) of moderate differentiation. Surgical resection was performed through a minimally invasive approach with a favourable postoperative course and a short hospital stay. One-month Post-operative Octreotide scan showed no extrahepatic primary origin of the tumour.

Discussion

PHNET is a rare entity, and multi modalities investigations, including imaging, serology, endoscopy series, and histopathology findings, aside from long-term follow-up to rule out another primary origin, are essential for the final diagnosis of PHNET. Surgical resection stands as the mainstay of treatment of PHNETs.

Conclusion

The absence of primary liver diseases should expand our possible differential diagnosis. Laparoscopic surgical resection of PHNETs carries a favourable outcome.
Validation of a Farsi version of the Eating Disorder Examination Questionnaire (F-EDE-Q) in adolescents and university students from Iran
Authors: Sahlan Reza N. , Saunders Jessica F. , Klimek-Johnson Patrycja , Convertino Alexandra D. , Lavender Jason M. , Fitzsimmons-Craft Ellen E. , Nagata Jason M.
Published: June 2023

Background

Although the Farsi version of the Eating Disorder Examination-Questionnaire (F-EDE-Q) is frequently utilized to assess disordered eating in Iran, its factor structure, reliability, and validity have not been investigated in Iranian samples, which is the aim of the current investigation.

Method

Using convenience sampling, this study recruited 1112 adolescents and 637 university students to complete disordered eating and mental health-focused questionnaires, including the F-EDE-Q.

Results

Confirmatory factor analyses of the 22 attitudinal items in the F-EDE-Q indicated that a brief seven-item, three-factor model (i.e., Dietary Restraint, Shape/Weight Overvaluation, Body Dissatisfaction with Shape and Weight) was the only factor structure that fit the data well for either sample. This brief version of the F-EDE-Q was invariant across gender, body weight, and age. Adolescent and university participants with higher weight reported higher average scores on each of the three subscales. Subscale scores showed good internal consistency reliability in the two samples. Further, supporting convergent validity, subscales were significantly associated with measures of body image-related preoccupation and bulimia symptoms, as well as measures of other theoretically related constructs including depressive symptoms and self-esteem.

Conclusion

Findings suggest that this brief, validated measure will enable researchers and clinical providers to appropriately assess disordered eating symptoms in adolescent and young adult Farsi-speaking populations.
Cancer metabolites: promising biomarkers for cancer liquid biopsy
Authors: Wang Wenxiang , Rong Zhiwei , Wang Guangxi , Hou Yan , Yang Fan , Qiu Mantang
Published: June 2023

Cancer exerts a multitude of effects on metabolism, including the reprogramming of cellular metabolic pathways and alterations in metabolites that facilitate inappropriate proliferation of cancer cells and adaptation to the tumor microenvironment. There is a growing body of evidence suggesting that aberrant metabolites play pivotal roles in tumorigenesis and metastasis, and have the potential to serve as biomarkers for personalized cancer therapy. Importantly, high-throughput metabolomics detection techniques and machine learning approaches offer tremendous potential for clinical oncology by enabling the identification of cancer-specific metabolites. Emerging research indicates that circulating metabolites have great promise as noninvasive biomarkers for cancer detection. Therefore, this review summarizes reported abnormal cancer-related metabolites in the last decade and highlights the application of metabolomics in liquid biopsy, including detection specimens, technologies, methods, and challenges. The review provides insights into cancer metabolites as a promising tool for clinical applications.
A voluntary-sector meeting place as a site for interpreting and ‘doing’ integration: a case of later-life Russian-speaking migrants
Authors: Asikainen Anastasia
Published: June 2023

While a great deal of research has been conducted on implications of integrative policies targeted at migrants, later-life migrants and their relational and spatial negotiations and enactments of the policy-driven discourse of integration, and the dynamics under which it is interpreted remains understudied. Older migrants are presented as ‘special cases’ in the Finnish integration policy and are discussed mainly in relation to their social and health care needs. Integration is the model and aim for migrant settlements in Finland, however the aim to integrate possesses intrinsic value. Therefore, they need to make sense of what integration is for them in their everyday lives. This paper focuses on the interpretations and mundane enactments of ‘integration’ in a voluntary sector-organised meeting place for later-life Russian-speaking migrants in Finland. By comparing the views of different actors within the meeting place (steering group, organisers and attendees), the paper presents a nuanced understanding of the dynamics under which the later-life migrants negotiate their positions in the Finnish community of value, vis-à-vis the expectations of integration. The paper argues that ‘doing integration’ as a category of practice is an emergent feature in places where it is possible to negotiate integration as a lived experience. Drawing from participant observations, interviews, and applications and reports gathered in a meeting in the capital region of Finland, the paper foregrounds the lived and contested experiences of finding a sense of belonging in dialogue with the omnipresent discourse of integration. The paper concludes that the interpretations of the policy-driven discourse of integration are context-bound and negotiated in a set of relationships.
First preclinical evaluation of [225Ac]Ac-DOTA-JR11 and comparison with [177Lu]Lu-DOTA-JR11, alpha versus beta radionuclide therapy of NETs
Authors: Handula Maryana , Beekman Savanne , Konijnenberg Mark , Stuurman Debra , de Ridder Corrina , Bruchertseifer Frank , Morgenstern Alfred , Denkova Antonia , de Blois Erik , Seimbille Yann
Published: June 2023

Background

The [177Lu]Lu-DOTA-TATE mediated peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) is sometimes leading to treatment resistance and disease recurrence. An interesting alternative could be the somatostatin antagonist, [177Lu]Lu-DOTA-JR11, that demonstrated better biodistribution profile and higher tumor uptake than [177Lu]Lu-DOTA-TATE. Furthermore, treatment with alpha emitters showed improvement of the therapeutic index of PRRT due to the high LET offered by the alpha particles compared to beta emitters. Therefore, [225Ac]Ac-DOTA-JR11 can be a potential candidate to improve the treatment of NETs (Graphical abstract). DOTA-JR11 was radiolabeled with [225Ac]Ac(NO3)3 and [177Lu]LuCl3. Stability studies were performed in phosphate buffered saline (PBS) and mouse serum. In vitro competitive binding assay has been carried out in U2OS-SSTR2 + cells for natLa-DOTA-JR11, natLu-DOTA-JR11 and DOTA-JR11. Ex vivo biodistribution studies were performed in mice inoculated with H69 cells at 4, 24, 48 and 72 h after injection of [225Ac]Ac-DOTA-JR11. A blocking group was included to verify uptake specificity. Dosimetry of selected organs was determined for [225Ac]Ac-DOTA-JR11 and [177Lu]Lu-DOTA-JR11.

Results

[225Ac]Ac-DOTA-JR11 has been successfully prepared and obtained in high radiochemical yield (RCY; 95%) and radiochemical purity (RCP; 94%). [225Ac]Ac-DOTA-JR11 showed reasonably good stability in PBS (77% intact radiopeptide at 24 h after incubation) and in mouse serum (~ 81% intact radiopeptide 24 h after incubation). [177Lu]Lu-DOTA-JR11 demonstrated excellent stability in both media (> 93%) up to 24 h post incubation. Competitive binding assay revealed that complexation of DOTA-JR11 with natLa and natLu did not affect its binding affinity to SSTR2. Similar biodistribution profiles were observed for both radiopeptides, however, higher uptake was noticed in the kidneys, liver and bone for [225Ac]Ac-DOTA-JR11 than [177Lu]Lu-DOTA-JR11.

Conclusion

[225Ac]Ac-DOTA-JR11 showed a higher absorbed dose in the kidneys compared to [177Lu]Lu-DOTA-JR11, which may limit further studies with this radiopeptide. However, several strategies can be explored to reduce nephrotoxicity and offer opportunities for future clinical investigations with [225Ac]Ac-DOTA-JR11.
Stem cell-based drug delivery strategy for skin regeneration and wound healing: potential clinical applications
Authors: Zhang Weiyue , Huang Xin
Published: June 2023

Stem cell-based therapy is widely accepted to be a promising strategy in tissue regenerative medicine. Nevertheless, there are several obstacles to applying stem cells in skin regeneration and wound healing, which includes determining the optimum source, the processing and administration methods of stem cells, and the survival and functions of stem cells in wound sites. Owing to the limitations of applying stem cells directly, this review aims to discuss several stem cell-based drug delivery strategies in skin regeneration and wound healing and their potential clinical applications. We introduced diverse types of stem cells and their roles in wound repair. Moreover, the stem cell-based drug delivery systems including stem cell membrane-coated nanoparticles, stem cell-derived extracellular vesicles, stem cell as drug carriers, scaffold-free stem cell sheets, and stem cell-laden scaffolds were further investigated in the field of skin regeneration and wound healing. More importantly, stem cell membrane-coating nanotechnology confers great advantages compared to other drug delivery systems in a broad field of biomedical contexts. Taken together, the stem cell-based drug delivery strategy holds great promise for treating skin regeneration and wound healing.
The REBURN model: simulating system-level forest succession and wildfire dynamics
Authors: Prichard Susan J. , Salter R. Brion , Hessburg Paul F. , Povak Nicholas A. , Gray Robert W.
Published: June 2023

Background

Historically, reburn dynamics from cultural and lightning ignitions were central to the ecology of fire in the western United States (wUS), whereby past fire effects limited future fire growth and severity. Over millennia, reburns created heterogenous patchworks of vegetation and fuels that provided avenues and impediments to the flow of future fires, and feedbacks to future fire event sizes and their severity patterns. These dynamics have been significantly altered after more than a century of settler colonization, fire exclusion, and past forest management, now compounded by rapid climatic warming. Under climate change, the area impacted by large and severe wildfires will likely increase — with further implications for self-regulating properties of affected systems. An in-depth understanding of the ecology of reburns and their influence on system-level dynamics provides a baseline for understanding current and future landscape fire-vegetation interactions.

Results

Here, we present a detailed characterization of REBURN — a geospatial modeling framework designed to simulate reburn dynamics over large areas and long time frames. We interpret fire-vegetation dynamics for a large testbed landscape in eastern Washington State, USA. The landscape is comprised of common temperate forest and nonforest vegetation types distributed along broad topo-edaphic gradients. Each pixel in a vegetation type is represented by a pathway group (PWG), which assigns a specific state-transition model (STM) based on that pixel’s biophysical setting. STMs represent daily simulated and annually summarized vegetation and fuel succession, and wildfire effects on forest and nonforest succession. Wildfire dynamics are driven by annual ignitions, fire weather and topographic conditions, and annual vegetation and fuel successional states of burned and unburned pixels.

Conclusions

Our simulation study is the first to evaluate how fire exclusion and forest management altered the active fire regime of this landscape, its surface and canopy fuel patterns, forest and nonforest structural conditions, and the dynamics of forest reburning. The REBURN framework is now being used in related studies to evaluate future climate change scenarios and compare the efficacy of fire and fuel management strategies that either enable the return of active fire regimes or depend on fire suppression and wildfire effects on forest burning.
Laboratory study of metakaolin and microsilica effect on the performance of high-strength concrete containing Forta fibers
Authors: Faghihmaleki Hadi , Nazari Hossien
Published: June 2023

In the present study aims to produce high-strength fiber concrete containing microsilica and metakaolin. Eight concrete mixing samples have been defined. The samples include the control concrete with ordinary Portland cement, replacing 10 percent of the weight of cement with microsilica. The amount of microsilica was kept constant in the next six designs. Three samples with the addition of Forta fibers at the rate of 0.2, 0.5, and 0.8 percent. Finally three samples with 0.5% Forta fibers and 8, 10 and 12% metakaolin were subjected to compressive, tensile and elastic modulus tests at the ages of 7 and 28 days. The addition of Forta fibers and the replacement of microsilica and metakaolin in concrete reduced the slump of concrete up to 5 cm. The highest compressive strength, tensile strength and elastic modulus at the age of 28 days of design 8 (concrete containing 10% microsilica, 0.5% Forte fibers and 12% metakaolin) are respectively equal to 73.6 MPa, 5.55 MPa and 37.49 MPa with The increase was 19.43%, 32.77% and 15.21% compared to control concrete without pozzolan and additives. Also, the relationship between compressive and tensile strength were presented. In total, all samples containing microsilica and fibers had a favorable effect on the resistance properties of concrete compared to the control design. The constant concern of bridge engineers, especially concrete bridges, is the production of concrete with high-strength and very low permeability in the face of their surroundings. Therefore, the result of this research can be a significant contribution to improving the quality of concrete used in bridge constructions.
Traits of Patients With Pituitary Tumors in Multiple Endocrine Neoplasia Type 1 and Comparing Different Mutation Status
Authors: Lin Kuan-Yu , Kuo Yu-Ting , Cheng Mei-Fang , Chen Pei-Lung , Wang Hsiu-Po , Cheng Tsu-Yao , Chang Chia-Hsuin , Kao Hsiang-Fong , Yang Shih-Hung , Li Hung-Yuan , Lin Chia-Hung , Chou Yuh-Tsyr , Chung An-Ko , Wu Wan-Chen , Lu Jin-Ying , Wang Chih-Yuan , Hsih Wen-Hui , Wen Chen-Yu , Yang Wei-Shiung , Shih Shyang-Rong
Published: June 2023

Context

Recent studies suggest that the clinical characteristics and biological behavior of pituitary tumors (PITs) in patients with multiple endocrine neoplasia type 1 (MEN1) may not be as aggressive as previously reported. Increased imaging of the pituitary as recommended by screening guidelines identifies more tumors, potentially at an earlier stage. However, it is unknown if these tumors have different clinical characteristics in different MEN1 mutations.

Objective

To assess characteristics of patients with MEN1 with and without PITs, and compare among different MEN1 mutations.

Methods

Data of patients with MEN1 in a tertiary referral center from 2010 to 2023 were retrospectively analyzed.

Results

Forty-two patients with MEN1 were included. Twenty-four patients had PITs, 3 of which were invasive and managed with transsphenoidal surgery. One PIT enlarged during follow-up. Patients with PITs had a higher median age at MEN1 diagnosis than those without PITs. MEN1 mutations were identified in 57.1% of patients, including 5 novel mutations. In patients with PITs, those with MEN1 mutations (mutation+/PIT+ group) had more additional MEN1-associated tumors than those without (mutation−/PIT+ group). The mutation+/PIT+ group had a higher incidence of adrenal tumors and a lower median age at initial manifestation of MEN1 than the mutation−/PIT+ group. The most common neuroendocrine neoplasm was nonfunctional in the mutation+/PIT+ group and insulin-secreting in the mutation−/PIT+ group.

Conclusion

This is the first study comparing characteristics of patients with MEN1 with and without PITs harboring different mutations. Patients without MEN1 mutations tended to have less organ involvement and it might be reasonable for them to receive less intensive follow-up.
Gestational Transient Thyrotoxicosis Complicated by Thyroid Storm in a Patient With Hyperemesis Gravidarum
Authors: Villavicencio Camila A , Franco-Akel Alberto , Belokovskaya Regina
Published: June 2023

We describe a patient with gestational transient thyrotoxicosis (GTT) associated with hyperemesis gravidarum (HG) in a twin gestation complicated by thyroid storm resulting in intrauterine fetal demise. GTT is a well-documented complication of the first trimester of pregnancy that may affect up to 60% of pregnancies with HG. Typically, GTT is not associated with unfavorable maternal or fetal outcomes and has a spontaneous resolution. Aside from supportive care, the use of antithyroid drugs (ATD) in GTT is not regularly recommended. Although to our knowledge one similar case has been reported in the literature, the incidence of thyroid storm in GTT has not yet been established. Our case highlights that, although rare, GTT may be complicated by thyroid storm resulting in adverse maternal and fetal outcomes. Our case further suggests that consideration of ATD use in GTT should be given in pregnancies with higher serum human chorionic gonadotropin (hCG) concentration as occurs in HG and multiple pregnancies.
Topological Data Analysis and Use of Mapper for Cerebral Aneurysm Rupture Status Discrimination Based on 3-Dimensional Shape Analysis
Authors: Lauric Alexandra , Ludwig Calvin G. , Malek Adel M.
Published: June 2023

BACKGROUND AND OBJECTIVES:

Topological data analysis (TDA), which identifies patterns in data through simplified topological signatures, has yet to be applied to aneurysm research. We investigate TDA Mapper graphs (Mapper) for aneurysm rupture discrimination.

METHODS:

Two hundred sixteen bifurcation aneurysms (90 ruptured) from 3-dimensional rotational angiography were segmented from vasculature and evaluated for 12 size/shape and 18 enhanced radiomics features. Using Mapper, uniformly dense aneurysm models were represented as graph structures and described by graph shape metrics. Mapper dissimilarity scores (MDS) were computed between pairs of aneurysms based on shape metrics. Lower MDS described similar shapes, whereas high MDS represented shapes that do not share common characteristics. Ruptured/unruptured average MDS scores (how “far” an aneurysm is shape-wise to ruptured/unruptured data sets, respectively) were evaluated for each aneurysm. Rupture status discrimination univariate and multivariate statistics were reported for all features.

RESULTS:

The average MDS for pairs of ruptured aneurysms were significantly larger compared with unruptured pairs (0.055 ± 0.027 vs 0.039 ± 0.015, P < .0001). Low MDS suggest that, in contrast to ruptured aneurysms, unruptured aneurysms have similar shape characteristics. An MDS threshold value of 0.0417 (area under the curve [AUC] = 0.73, 80% specificity, 60% sensitivity) was identified for rupture status classification. Under this predictive model, MDS scores <0.0417 would identify unruptured status. MDS statistical performance in discriminating rupture status was similar to that of nonsphericity and radiomics Flatness (AUC = 0.73), outperforming other features. Ruptured aneurysms were more elongated (P < .0001), flatter (P < .0001), and showed higher nonsphericity (P < .0001) compared with unruptured. Including MDS in multivariate analysis resulted in AUC = 0.82, outperforming multivariate analysis on size/shape (AUC = 0.76) and enhanced radiomics (AUC = 0.78) alone.

CONCLUSION:

A novel application of Mapper TDA was proposed for aneurysm evaluation, with promising results for rupture status classification. Multivariate analysis incorporating Mapper resulted in high accuracy, which is particularly important given that bifurcation aneurysms are challenging to classify morphologically. This proof-of-concept study warrants future investigation into optimizing Mapper functionality for aneurysm research.
Recurrent Chronic Subdural Hematoma After Burr-Hole Surgery and Postoperative Drainage: A Systematic Review and Meta-Analysis
Authors: Lodewijkx Roger , Foppen Merijn , Slot Kari-Anne Mariam , Vandertop William Peter , Verbaan Dagmar
Published: June 2023

BACKGROUND AND OBJECTIVE:

Reported recurrence rates of chronic subdural hematoma treated by burr-hole surgery with postoperative drainage vary considerably in the literature. We performed a systematic review and meta-analysis to define the recurrence rate of burr-hole surgery with postoperative drainage.

METHODS:

PubMed and EMBASE were searched, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. We used the Newcastle-Ottawa scale and Cochrane risk-of-bias tool for quality assessment of included studies and the random-effects model to calculate pooled incidence rates in R with the metaprop function if appropriate.

RESULTS:

The search yielded 2969 references; 709 were screened full text, and 189 met the inclusion criteria. In 174 studies (34 393 patients), the number of recurrences was reported as per patient and 15 studies (3078 hematomas) reported the number of recurrences per hematoma, for a pooled incidence of 11.2% (95% CI: 10.3-12.1; I2= 87.7%) and 11.0% (95% CI: 8.6-13.4; I2= 78.0%), respectively. The pooled incidence of 48 studies (15 298 patients) with the highest quality was 12.8% (95% CI 11.4-14.2; I2= 86.1%). Treatment-related mortality (56 patients) has a pooled incidence of 0.7% (95% CI 0.0-1.4; I2= 0.0%).

CONCLUSION:

The recurrence rate of chronic subdural hematoma treated by burr-hole surgery and postoperative drainage is 12.8%.
Expansion and Subsequent Rupture of Carotid Pseudoaneurysm After Tandem Carotid and Middle Cerebral Artery Occlusion Treated With Mechanical Thrombectomy and Carotid Stenting
Authors: Housley Steven B. , Turner Ryan C. , Bouslama Mehdi , Lim Jaims , Raygor Kunal P. , Lai Pui Man Rosalind , Monteiro Andre , Baig Ammad A. , Nyabuto Elizabeth , Davies Jason M. , Siddiqui Adnan H. , Snyder Kenneth V. , Levy Elad I.
Published: June 2023

BACKGROUND AND IMPORTANCE:

Extracranial carotid artery pseudoaneurysm is a rare entity with potential etiologies including infection, blunt trauma, postsurgical atherosclerotic disease, and invasive neoplasia. Although the natural history of carotid pseudoaneurysm is difficult to determine because of its rarity, complications such as stroke, rupture, and local mass effect may occur at staggering rates.

CLINICAL PRESENTATION:

In this case, a middle-aged man presented with a tandem carotid, middle cerebral artery occlusion that was treated with a carotid stent and mechanical thrombectomy. He returned 3 weeks later with a ruptured carotid pseudoaneurysm that was then treated with a covered stent. He made a full recovery and was neurologically intact on follow-up.

CONCLUSION:

This case illustrates a rare potential complication of carotid occlusion and stenting with possible catastrophic consequences. The goal of this report was to educate other clinicians in remaining vigilant in awareness of this complication and provide a framework for potential treatment if and when it occurs.
Labor Market Responses to Unemployment Insurance: The Role of Heterogeneity
Authors: Birinci Serdar , See Kurt
Published: June 2023

We document considerable scope of heterogeneity within the unemployed, especially when they are divided along eligibility for and receipt of unemployment insurance (UI). We study the implications of this heterogeneity on UI’s insurance-incentive trade-off using a heterogeneous-agent job search model capable of matching the wealth and income differences that distinguish UI recipients from nonrecipients. Insurance benefits are larger for UI recipients who are predominantly wealth poor. Meanwhile, incentive costs are nonmonotonic in wealth because the poorest individuals, who value employment, exhibit weak responses. Differential elasticities imply that accounting for the composition of recipients is material to the evaluation of UI’s insurance-incentive trade-off. (JEL D91, E24, E32, J64, J65)
Evaluation by app in smartphones of awake bruxism at the return of presential classes in two university centers
Authors: Velasquez Ron Byron , Mosquera Cisneros Veronica , Pazmiño Troncoso Pamela , Rodriguez Tates Maria , Alvares Lalvay Eddy , Chauca  Bajaña Luis , Ordoñez Balladares Andrea
Published: June 2023

Background. The return to normality post-pandemic brought some inconveniences to the population, especially students. To evaluate the frequency of awake bruxism behaviors through the use of an app on smartphones in dental students returning to presential classes.  Awake bruxism was evaluated with the creation of an app that according to the authors evaluates: relaxed jaw muscles, dental contact, jaw effort, clenching teeth and teeth grinding, 5 frequent oral conditions in the population. The frequency of awake/daytime bruxism (AB) in  healthy individuals when comparing other populations with possible risk factors for additive bruxism (psychological factors, depression, suicide delusions, etc.), evaluating consequent clinical signs (fatigue, muscle pain, attritions and dental openings). 

Methods: The sample of three hundred (n=300) young adults legally enrolled in two Ecuadorian universities, the sample was selected among fifth, sixth, seventh, eighth and ninth semester students legally enrolled and who are attending Faculty of  Dentistry classes in 2 different cities (Quito and Guayaquil). The app was configured to provide 20 alerts during the day x seven days a week, in real time.

Results. The study obtained 95% reliability and 5% error in research, was used. The relaxation condition was present in all users, but 40% of the alerts were associated with jaw and tooth discomfort, 39% corresponded to the discomfort of mandibular clenching, and 24% corresponded to tooth contact. A direct significant association was found between the state of relaxation and nonrelaxation, with a high probability of reports related to nonrelaxation (p ≤ 0.05).

Conclusions: Awake bruxism with the app  was evaluated, identifying 5 behaviors such as: relaxed mandibular muscles, dental contact, mandibular effort, clenching and grinding teeth, frequent conditions in the population; reporting a state of mandibular relaxation, there is a high probability that a condition of nonrelaxation would be reported (p≤0.05).
Breakthrough pain and rapid-onset opioids in patients with cancer pain: a narrative review
Authors: Yeo Jinseok
Published: June 2023

Breakthrough pain is transitory pain that occurs despite the use of opioids for background pain control. Breakthrough pain occurs in 40% to 80% of patients with cancer pain. Despite effective analgesic therapy, patients and their caregivers often feel that their pain is not sufficiently controlled. Therefore, an improved understanding of breakthrough pain and its management is essential for all physicians caring for patients with cancer. This article reviews the definition, clinical manifestations, accurate diagnostic strategies, and optimal treatment options for breakthrough pain in patients with cancer. This review focuses on the efficacy and safety of rapid-onset opioids, which are the primary rescue drugs for breakthrough pain.