bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO-035: Immune profiles of long-term survivors of patients with head and neck squamous carcinoma on immune checkpoint inhibitor therapy
Authors: Christensen Brock , Lee Min Kyung , Zhang Ze , Butler Rondi , Ramush Geat , Sehgal Kartik , Shirai Keisuke , Koestler Devin , Salas Lucas , Wiencke John , Haddad Robert , Kelsey Karl
Published: September 2023

Background: Only 15 – 20% of patients with head and neck squamous cell carcinoma (HNSCC) have response to anti-programmed cell death (PD)-1 immunotherapy and there remain gaps in predicting which patients will respond. Method: Here, we utilized DNA methylation cytometry to sequentially delineate detailed immune profiles of six patients with HNSCC (n=38 samples), who had durable response to immunotherapy over a one-year period without disease progression. Results: During the initial 3.5 months of anti-PD-1 immunotherapy treatment, increases in levels of CD8 T memory cells and natural killer cells were observed. Compared to healthy populations in similar age ranges, CD4 T and B cell levels were lower, while monocyte levels were higher in patients with HNSCC at baseline and throughout the year of treatment with immunotherapy. Conclusions: Our results suggest monitoring changes in immune cell type levels as potential biomarkers for patients with HNSCC who respond to anti-PD-1 immunotherapy.

Citation Format: Brock Christensen, Min Kyung Lee, Ze Zhang, Rondi Butler, Geat Ramush, Kartik Sehgal, Keisuke Shirai, Devin Koestler, Lucas Salas, John Wiencke, Robert Haddad, Karl Kelsey. Immune profiles of long-term survivors of patients with head and neck squamous carcinoma on immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-035.
Abstract PR03: Cholinergic modulation of tumor infiltrating lymphocytes in oral squamous cell carcinoma
Authors: White Ruth A.
Published: September 2023

Response to immunotherapy remains less than 20% for Oral Cavity Squamous Cell Carcinoma (OSCC). The poor response is in part due to dysfunctional cytotoxic T cell activity resulting from terminal exhaustion as a response to chronic exposure to tumor antigen. New strategies are needed to sensitize OSCC to immunotherapy to improve response rates and overall survival. Stimulation of muscarinic receptors by Acetylcholine (Ach), the primary neurotransmitter of the parasympathetic nervous system, restrains pancreatic and breast cancer but promotes gastric and late stage prostate cancer. The role of cholinergic signaling in OSCC is unknown. Ach can be secreted from non-neuronal tissues, including lymphocytes, which are abundant in the OSCC microenvironment. These lymphocytes express choline acetyltransferase (ChaT), the enzyme catalyzing the rate limiting step of Ach production and are important in maintaining chronic anti-viral immune responses. Our objective is to uncover the role of these Ach secreting T cells in mediating the anti-tumor immune response in OSCC. We utilized the 4MOSC1 and 4MOSC2 orthotopic OSCC tumor model. Orthotopic tumors were generated in recipient mice with impaired Ach-muscarinic signaling. ChaT+ CD8+ T cells were amplified in the tumor microenvironment and in vitro after activation. Inhibition of Ach-muscarinic signaling in the tumor immune microenvironment (TIME) accelerated tumor growth kinetics and was associated with loss of tumor infiltrating lymphocytes (TILs). Analysis of T cell activation states in TILs and after in vitro activation demonstrated that disruption of Ach-muscarinic signaling promotes differentiation of effector T lymphocytes at the expense of central memory. These data suggest that the Ach-muscarinic axis promotes CD8+ T cell infiltration and maintains T cell memory in the TIME supporting long term anti-tumor immune responses.

Citation Format: Ruth A. White. Cholinergic modulation of tumor infiltrating lymphocytes in oral squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PR03.
Os processos de desenvolvimento do site Precisa Cantar, Senhora?
Authors: Rangel Débora Rodrigues , Lackschevitz Eduardo
Published: September 2023

Descrição do processo de pesquisa e construção do site XXX para apoio a educadores musicais e regentes corais, que teve como base a metodologia Design Science Research. O projeto traz diversas narrativas e estudos de caso baseados na experiência da pesquisadora à frente de classes de canto coral juvenil em entidades socioeducativas. Tais histórias abordam questões de ordem comportamental, social e institucional relacionadas ao canto coral. O usuário tem acesso gratuito a oito casos através de diferentes materiais multimídia e pode interagir com a pesquisadora pelas redes sociais compartilhando suas próprias experiências e discutindo os casos com outros profissionais.
ANGPTL3 Deficiency and Risk of Hepatic Steatosis
Authors: D’Erasmo Laura , Di Martino Michele , Neufeld Thomas , Fraum Tyler J. , Kang Chul Joo , Burks Kendall H. , Di Costanzo Alessia , Minicocci Ilenia , Bini Simone , Maranghi Marianna , Pigna Giovanni , Labbadia Giancarlo , Zheng Jie , Fierro Davide , Montali Anna , Ceci Fabrizio , Catalano Carlo , Davidson Nicholas O. , Lucisano Giuseppe , Nicolucci Antonio , Arca Marcello , Stitziel Nathan O.
Published: September 2023

BACKGROUND:

ANGPTL3 (angiopoietin-like 3) is a therapeutic target for reducing plasma levels of triglycerides and low-density lipoprotein cholesterol. A recent trial with vupanorsen, an antisense oligonucleotide targeting hepatic production of ANGPTL3, reported a dose-dependent increase in hepatic fat. It is unclear whether this adverse effect is due to an on-target effect of inhibiting hepatic ANGPTL3.

METHODS:

We recruited participants with ANGPTL3 deficiency related to
ANGPTL3
loss-of-function (LoF) mutations, along with wild-type (WT) participants from 2 previously characterized cohorts located in Campodimele, Italy, and St. Louis, MO. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction were performed to measure hepatic fat fraction and the distribution of extrahepatic fat. To estimate the causal relationship between ANGPTL3 and hepatic fat, we generated a genetic instrument of plasma ANGPTL3 levels as a surrogate for hepatic protein synthesis and performed Mendelian randomization analyses with hepatic fat in the UK Biobank study.

RESULTS:

We recruited participants with complete (n=6) or partial (n=32) ANGPTL3 deficiency related to
ANGPTL3
LoF mutations, as well as WT participants (n=92) without LoF mutations. Participants with ANGPTL3 deficiency exhibited significantly lower total cholesterol (complete deficiency, 78.5 mg/dL; partial deficiency, 172 mg/dL; WT, 188 mg/dL;
P
<0.05 for both deficiency groups compared with WT), along with plasma triglycerides (complete deficiency, 26 mg/dL; partial deficiency, 79 mg/dL; WT, 88 mg/dL;
P
<0.05 for both deficiency groups compared with WT) without any significant difference in hepatic fat (complete deficiency, 9.8%; partial deficiency, 10.1%; WT, 9.9%;
P
>0.05 for both deficiency groups compared with WT) or severity of hepatic steatosis as assessed by magnetic resonance imaging. In addition, ANGPTL3 deficiency did not alter the distribution of extrahepatic fat. Results from Mendelian randomization analyses in 36 703 participants from the UK Biobank demonstrated that genetically determined ANGPTL3 plasma protein levels were causally associated with low-density lipoprotein cholesterol (
P
=1.7×10
-17
) and triglycerides (
P
=3.2×10
-18
) but not with hepatic fat (
P
=0.22).

CONCLUSIONS:

ANGPTL3 deficiency related to LoF mutations in
ANGPTL3
, as well as genetically determined reduction of plasma ANGPTL3 levels, is not associated with hepatic steatosis. Therapeutic approaches to inhibit ANGPTL3 production in hepatocytes are not necessarily expected to result in the increased risk for hepatic steatosis that was observed with vupanorsen.
Atoms for Industry: The Early Nuclear Activities of Fiat and the Atoms for Peace Program in Italy, 1956–1959
Authors: Curli Barbara
Published: September 2023

Fiat's nuclear activities began in the immediate postwar period, when the company financed initiatives meant to reconstruct applied and theoretical research on nuclear physics in Italy. However, its actual industrial involvement originated in the framework of the Atoms for Peace initiative, which provided the opportunity for the purchase of an American Machine and Foundry pool-type reactor for a research center founded by Società Ricerche Impianti Nucleari (SORIN), a joint-venture created in 1956 by Fiat and the Italian chemical company Montecatini. SORIN developed know-how and technology in the electromechanical and biomedical industries. The SORIN center was the first private initiative within the Atoms for Peace framework. This article is a first attempt to assess Fiat's involvement in the nuclear sector, shedding light on the reception of Atoms for Peace in Italy and the way various actors on the Italian nuclear scene used it to pursue their own objectives during the Cold War.
Morphological and molecular characterization of the Makran Glossogobius cf. giuris (Teleostei: Gobiidae) and the Glossogobius giuris species complex taxonomy
Authors: ZAREI FATAH , KOVAČIĆ MARCELO , ESMAEILI HAMID REZA , GHANBARIFARDI MEHDI
Published: September 2023

The Indo-West Pacific Glossogobius giuris (Hamilton, 1822) species complex has four spatially circumscribed independent lineages, partially taxonomically resolved. A sample of gobies from the G. giuris species complex was recently collected from the Makran River System, south-eastern Iran, which drains into the northern Oman Sea. The taxonomic status of this population was clarified using a molecular and morphological framework. Molecular and morphological data both revealed that the examined sample from the Makran River System is conspecific with G. giuris B which is widely distributed in the coastal habitats and basins of the Indian Ocean. In addition, consensus from different molecular species delimitations, K2P genetic distance, and tree topologies confirmed the four lineages of the G. giuris species complex as distinct taxonomic entities, hereby highlighting the necessity of an integrative morphological and molecular approach to complete the clarification of taxonomic diversity within this group. Glossogobius giuris species complex taxonomy is discussed and solution recommended.
Additional records and poorly known species of Kamimuria Klapálek, 1907 (Plecoptera, Perlidae) from southern China
Authors: LI KEFAN , WANG BINGLI , BOZDOĞAN HAKAN , LI WEIHAI
Published: September 2023

Two poorly known species of Kamimuria Klapálek, 1907 originally known from southern China, K. melli Wu, 1935 and K. taoi Wu, 1936, are rediscovered and amended with supplementary descriptions of the aedeagi. Kamimuria atra Sivec & Stark, 2008 is recorded for the first time from China. Kamimuria liui (Wu, 1940) is newly recorded from southern China, amended with descriptions of the aedeagus and noted morphological variability, and compared to related congeners. Digital micrographs of the adult male, including the fully extruded aedeagi, are presented for the first time for the above four species.
A new genus and endangered species of euptychiine butterfly from isolated mountains in southeastern Brazil (Lepidoptera: Nymphalidae: Satyrinae)
Authors: ZACCA THAMARA , CORDEIRO DANILO PACHECO , GONELLA PAULO MINATEL
Published: September 2023

Agojie rupicola gen. et sp. nov., a new genus and species of Euptychiina from the campos rupestres and granitic inselbergs of eastern Minas Gerais, southeastern Brazil, is herein described using comparative morphology and ecological data. Diagnoses, photos, and illustrations are also provided, in addition to a discussion on the putative systematic placement of the new taxa and its conservation status. Considering the collecting points, the estimated value for the extent of occurrence (EOO) is 100.263 km2 and the area of occupancy (AOO) is 20 km2, which combined with the reduced number of localities in which the species is known to occur, and the observed continuing decline of the quality of the habitat, we recommend that A. rupicola gen. et sp. nov. should be formally assessed as Endangered based on criteria B1+2(a,biii) of the International Union for Conservation of Nature (IUCN). The results presented here add to the increasing faunistic and floristic novelties that justify the priority for the conservation of these still scientifically underexplored Brazilian mountains.
Left ventricular remodelling in rheumatic heart disease – trends over time and implications for follow-up in childhood
Authors: MacDonald Bradley , Tarca Adrian , Causer Louise , Maslin Katie , Bruce Di , Schreiber-Wood Rachel , Kumar Mohit , Ramsay James , Andrews David , Budgeon Charley , Katzenellenbogen Judith , Bowen Asha C. , Carapetis Jonathan , Friedberg Mark K. , Yim Deane
Published: September 2023

Background

Rheumatic heart disease (RHD) is the most common form of acquired heart disease worldwide. In RHD, volume loading from mitral regurgitation leads to left ventricular (LV) dilatation, increased wall stress, and ultimately LV dysfunction. Improved understanding of LV dynamics may contribute to refined timing of intervention. We aimed to characterize and compare left ventricular remodelling between rheumatic heart disease (RHD) severity groups by way of serial echocardiographic assessment of volumes and function in children.

Methods

Children with RHD referred to Perth Children’s Hospital (formally Princess Margaret Hospital) (1987–2020) were reviewed. Patients with longitudinal pre-operative echocardiograms at diagnosis, approximately 12 months and at most recent follow-up, were included and stratified into RHD severity groups. Left ventricular (LV) echocardiographic parameters were assessed. Adjusted linear mixed effect models were used to compare interval changes.

Results

146 patients (median age 10 years, IQR 6–14 years) with available longitudinal echocardiograms were analysed. Eighty-five (58.2%) patients had mild, 33 (22.6%) moderate and 28 (19.2%) severe RHD at diagnosis. Mean duration of follow-up was 4.6 years from the initial diagnosis. Severe RHD patients had significantly increased end-systolic volumes (ESV) and end-diastolic volumes (EDV) compared to mild/moderate groups at diagnosis (severe versus mild EDV mean difference 27.05 ml/m2, p < 0.001, severe versus moderate EDV mean difference 14.95 ml/m2, p = 0.006). Mild and moderate groups experienced no significant progression of changes in volume measures. In severe RHD, LV dilatation worsened over time. All groups had preserved cardiac function.

Conclusions

In mild and moderate RHD, the lack of progression of valvular regurgitation and ventricular dimensions suggest a stable longer-term course. Significant LV remodelling occurred at baseline in severe RHD with progression of LV dilatation over time. LV function was preserved across all groups. Our findings may guide clinicians in deciding the frequency and timing of follow-up and may be of clinical utility during further reiterations of the Australia and New Zealand RHD Guidelines.
Giant coronary aneurysm of Behcet’s disease with sudden syncope: a case report
Authors: Feng Jingwei , Miao Qi , Zhang Chaoji
Published: September 2023

Behcet’s disease(BD) is a chronic inflammatory vasculitis that rarely affects the arteries, making myocardial infarction unlikely. We report a 28-year-old patient who was admitted to our hospital with multiple sudden syncope. Cardiovascular risk factors such as hypertension (HT), diabetes and obesity were not found in her. Preoperatively, imaging examinations suggested thrombosis of the inferior and superior vena cava and right heart combined with coronary artery aneurysm. The patient was finally diagnosed with a huge coronary artery aneurysm proximal to the left anterior descending artery. Syncope is considered to be caused right ventricular outflow tract obstruction. The patient received a successful aneurysm resection and had an uneventful postoperative recovery.
SASE, Success and Adverse event Score in Endoscopic Retrograde Cholangiopancreatography: a Novel Grading System
Authors: Maieron Andreas , Duller Christine , Püspök Andreas , Steiner Emanuel , Kapral Christine
Published: September 2023

Background

Validated, accepted grading tools for preprocedural complexity assessment in ERCP are lacking. We therefore created a grading system for ERCP based on the classification used by the American Society for Gastrointestinal Endoscopy (ASGE).

Methods

Data on ERCP adverse events (AE) and success were collected in a multicenter, prospective uncontrolled study. Multiple logistic regressions were applied to success and AEs in accordance with the ASGE classification. Each procedure suggested by ASGE was tested against different outcomes. Results were used to create a score and were evaluated in a control cohort.

Results

16,327 ERCPs were documented in 27 centers. Analysis of ASGE categorization (10,904 cases) showed that this model fails to adequately predict parameters of complexity; only for cardiopulmonary AEs and perforation was no significant variance evident. Depending on the specific clinical circumstances, probability of success of the intervention sometimes varied significantly in risk, implying a twofold score, one part for probability of success and one for risk. A split score with three levels each was designed and tested in a validation cohort (5,423 procedures). Achieving therapeutic targets / post-ERCP pancreatitis could be correctly predicted in 87.0%/95.3%.

Conclusions

Grading ERCP success and AEs have to be considered independently. Onefold grading systems appear incomplete and unable to provide an adequate classification of severity. SASE (Success and Adverse Event Score in Endoscopic Retrograde Cholangiopancreatography) was created to incorporate these findings. Showing high predictive value, this score could be a potent tool for planning ERCP and training in endoscopy.
Predictors and impact of trust on vaccine decisions in parents of 2-year-old children in Canada: findings from the 2017 Childhood National Immunization Coverage Survey (cNICS)
Authors: N Schellenberg , M Dietrich Leurer , P Petrucka , AM Crizzle
Published: September 2023

Trust is known to be an important factor in vaccine decisions for parents of young children, but there has been a lack of Canadian data measuring the determinants and impact of trust. Using data from the 2017 Canadian Childhood National Immunization Coverage Survey (cNICS), this study analyzed the relationships between sources that parents trust for vaccine information and demographics, parental knowledge, attitudes, and beliefs (KAB) and vaccine decisions (refusal, delay or reluctance) in parents of 2-year-old children who had accepted at least one vaccine for their child (n = 6125). The findings show that 83% of parents trust doctors for vaccine information; 70–80% trust pharmacists, PMH, nurses and HC/PHAC; 34% trust family and 23% trust friends and CAM HCPs. However, parents found to have poor or moderate KAB were less likely to trust doctors, nurses, pharmacists, PMH and HC/PHAC. Parents were also less likely to trust the PMH or HC/PHAC if they had high school education or less or trade/college education, or were widowed, separated, or divorced. Parents who had never been reluctant to vaccinate their 2-year-old child were over 2 times more likely to trust doctors, nurses, pharmacists, PMH and HC/PHAC while parents who trusted family and friends were less likely to delay or refuse vaccines. There was also significant regional variation within Canada, with parents from Quebec most likely to trust doctors, nurses, pharmacists, friends, PMH and HC/PHAC. Parents from the Territories were less likely to trust doctors, nurses and pharmacists, but more likely to trust family. Parents were less likely to trust doctors if they were from the Prairies, and pharmacists if they were from BC, and parents from the Prairies and BC were less likely to trust HC/PHAC. Parents from Ontario were less likely to trust family or friends, but more likely to trust the PMH. Tailored vaccine campaigns are needed to account for educational, marital, and regional differences across Canada to improve vaccine uptake.
Meta-analysis of integrated ChIP-seq and transcriptome data revealed genomic regions affected by estrogen receptor alpha in breast cancer
Authors: Piryaei Zeynab , Salehi Zahra , Ebrahimie Esmaeil , Ebrahimi Mansour , Kavousi Kaveh
Published: September 2023

Background

The largest group of patients with breast cancer are estrogen receptor-positive (ER+) type. The estrogen receptor acts as a transcription factor and triggers cell proliferation and differentiation. Hence, investigating ER-DNA interaction genomic regions can help identify genes directly regulated by ER and understand the mechanism of ER action in cancer progression.

Methods

In the present study, we employed a workflow to do a meta-analysis of ChIP-seq data of ER+ cell lines stimulated with 10 nM and 100 nM of E2. All publicly available data sets were re-analyzed with the same platform. Then, the known and unknown batch effects were removed. Finally, the meta-analysis was performed to obtain meta-differentially bound sites in estrogen-treated MCF7 cell lines compared to vehicles (as control). Also, the meta-analysis results were compared with the results of T47D cell lines for more precision. Enrichment analyses were also employed to find the functional importance of common meta-differentially bound sites and associated genes among both cell lines.

Results

Remarkably, POU5F1B, ZNF662, ZNF442, KIN, ZNF410, and SGSM2 transcription factors were recognized in the meta-analysis but not in individual studies. Enrichment of the meta-differentially bound sites resulted in the candidacy of pathways not previously reported in breast cancer. PCGF2, HNF1B, and ZBED6 transcription factors were also predicted through the enrichment analysis of associated genes. In addition, comparing the meta-analysis results of both ChIP-seq and RNA-seq data showed that many transcription factors affected by ER were up-regulated.

Conclusion

The meta-analysis of ChIP-seq data of estrogen-treated MCF7 cell line leads to the identification of new binding sites of ER that have not been previously reported. Also, enrichment of the meta-differentially bound sites and their associated genes revealed new terms and pathways involved in the development of breast cancer which should be examined in future in vitro and in vivo studies.
Three-dimensional analysis of the tricuspid annular geometry in healthy subjects and in patients with different grades of functional tricuspid regurgitation
Authors: Bieliauskienė Gintarė , Kažukauskienė Ieva , Kramena Rita , Zorinas Aleksejus , Mainelis Antanas , Zakarkaitė Diana
Published: September 2023

Background

Accurate sizing of the tricuspid valve annulus is essential for determining the optimal timing of tricuspid valve (TV) intervention. Two-dimensional (2D) echocardiography has limitations for comprehensive TV analysis. Three-dimensional (3D) imaging of the valve provides a better understanding of its spatial anatomy and enables more accurate measurements of TV structures.

Objectives

The study aimed to analyze tricuspid annulus (TA) parameters in normal heart and in different grades of functional tricuspid regurgitation (TR); to compare TA measurements obtained by 2D and 3D echocardiography.

Methods

One hundred fifty-five patients (median age 65 years, 57% women) with normal TV and different functional TR grades underwent 2D and 3D transthoracic echocardiography. The severity of TR was estimated using multiparametric assessment according to the guidelines. Mid-systolic 3D TA parameters were calculated using TV dedicated software. The conventional 2D systolic TA measurements in a standard four-chamber view were performed.

Results

In mid-systole, the normal TA area was 9.2 ± 2.0 cm2 for men and 7.4 ± 1.6 cm2 for women. When indexed to body surface area (BSA), there were no significant differences in the 3D parameters between genders. The 2D TA diameters were smaller than those measured in 3D. The ROC curve analysis identified that all 3D TA parameters can accurately differentiate between different functional TR grades. Additionally, the optimal cut-off values were identified for each TA parameter.

Conclusions

Gender, body size, and age have an impact on the TA parameters in healthy subjects. 2D measurements are smaller than 3D parameters. The reference values for 3D metrics according to TR severity can help in identifying TA dilation and distinguishing between different functional TR grades.

Graphical Abstract
Thermosensitive black phosphorus hydrogel loaded with silver sulfadiazine promotes skin wound healing
Authors: Zhou Jie , Li Tianjiao , Zhang Meili , Han Bo , Xia Tao , Ni Shuangshuang , Liu Zhiyong , Chen Zhenyang , Tian Xing
Published: September 2023

Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.
Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer’s disease diagnosis in clinically-relevant volumes of sample
Authors: Surpi Alessandro , Murgia Mauro , López-Amoedo Sonia , González-Gómez Manuel A. , Piñeiro Yolanda , Rivas José , Perugini Valeria , Santin Matteo , Sobrino Tomás , Greco Pierpaolo , Campos Francisco , Dediu Valentin Alek
Published: September 2023

Background

Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy in the elderly, implying a progressive cognitive decline and limitation of social activities. The progressive aging of the population is expected to exacerbate this problem in the next decades. Therefore, there is an urgent need to develop quantitative diagnostic methodologies to assess the onset the disease and its progression especially in the initial phases.

Results

Here we describe a novel technology to extract one of the most important molecular biomarkers of AD (Aβ1−42) from a clinically-relevant volume − 100 µl – therein dispersed in a range of concentrations critical for AD early diagnosis. We demonstrate that it is possible to immunocapture Aβ1−42 on 20 nm wide magnetic nanoparticles functionalized with hyperbranced KVLFF aptamers. Then, it is possible to transport them through microfluidic environments to a detection system where virtually all (~ 90%) the Aβ1−42 molecules are concentrated in a dense plug of ca.50 nl. The technology is based on magnetic actuation by permanent magnets, specifically designed to generate high gradient magnetic fields. These fields, applied through submillimeter-wide channels, can concentrate, and confine magnetic nanoparticles (MNPs) into a droplet with an optimized shape that maximizes the probability of capturing highly diluted molecular biomarkers. These advancements are expected to provide efficient protocols for the concentration and manipulation of molecular biomarkers from clinical samples, enhancing the accuracy and the sensitivity of diagnostic technologies.

Conclusions

This easy to automate technology allows an efficient separation of AD molecular biomarkers from volumes of biological solutions complying with the current clinical protocols and, ultimately, leads to accurate measurements of biomarkers. The technology paves a new way for a quantitative AD diagnosis at the earliest stage and it is also adaptable for the biomarker analysis of other pathologies.
SIRT1 activation promotes energy homeostasis and reprograms liver cancer metabolism
Authors: Varghese Benluvankar , Chianese Ugo , Capasso Lucia , Sian Veronica , Bontempo Paola , Conte Mariarosaria , Benedetti Rosaria , Altucci Lucia , Carafa Vincenzo , Nebbioso Angela
Published: September 2023

Background

Cancer cells are characterized by uncontrolled cell proliferation and impaired bioenergetics. Sirtuins are a family of highly conserved enzymes that play a fundamental role in energy metabolism regulation. SIRT1, in particular, drives many physiological stress responses and metabolic pathways following nutrient deprivation. We previously showed that SIRT1 activation using SCIC2.1 was able to attenuate genotoxic response and senescence. Here, we report that in hepatocellular carcinoma (HCC) cells under glucose-deprived conditions, SCIC2.1 treatment induced overexpression of SIRT1, SIRT3, and SIRT6, modulating metabolic response.

Methods

Flow cytometry was used to analyze the cell cycle. The MTT assay and xCELLigence system were used to measure cell viability and proliferation. In vitro enzymatic assays were carried out as directed by the manufacturer, and the absorbance was measured with an automated Infinite M1000 reader. Western blotting and immunoprecipitation were used to evaluate the expression of various proteins described in this study. The relative expression of genes was studied using real-time PCR. We employed a Seahorse XF24 Analyzer to determine the metabolic state of the cells. Oil Red O staining was used to measure lipid accumulation.

Results

SCIC2.1 significantly promoted mitochondrial biogenesis via the AMPK-p53-PGC1α pathway and enhanced mitochondrial ATP production under glucose deprivation. SIRT1 inhibition by Ex-527 further supported our hypothesis that metabolic effects are dependent on SIRT1 activation. Interestingly, SCIC2.1 reprogrammed glucose metabolism and fatty acid oxidation for bioenergetic circuits by repressing de novo lipogenesis. In addition, SCIC2.1-mediated SIRT1 activation strongly modulated antioxidant response through SIRT3 activation, and p53-dependent stress response via indirect recruitment of SIRT6.

Conclusion

Our results show that SCIC2.1 is able to promote energy homeostasis, attenuating metabolic stress under glucose deprivation via activation of SIRT1. These findings shed light on the metabolic action of SIRT1 in the pathogenesis of HCC and may help determine future therapies for this and, possibly, other metabolic diseases.
Negative correlation between central sensitization and forgotten joint score-12 after total hip arthroplasty
Authors: Imagama Takashi , Okazaki Tomoya , Matsuki Yuta , Kaneoka Takehiro , Kawakami Takehiro , Yamazaki Kazuhiro , Sakai Takashi
Published: September 2023

Background

Central sensitization is a condition in which even mild stimuli cause pain due to increased neuronal reactivity in the dorsal horn of the spinal cord. It is one of factors of chronic pain in patients with osteoarthritis. However, it is unknown whether central sensitization relates to clinical outcomes after total hip arthroplasty (THA). This study aimed to clarify whether preoperative central sensitization relates to the forgotten joint score-12 (FJS) after THA. Moreover, the secondary outcome was to identify which items in the FJS were most related by central sensitization.

Methods

This retrospective analysis included 263 hips (263 patients; 51 males and 212 females) that underwent primary THA in our institute and were available for evaluation one year postoperatively. The average patient age was 64.8 ± 11.9 years. The Central Sensitization Inventory (CSI) part A, which is a patient-reported outcome, was used to measure preoperative central sensitization. The correlation between preoperative CSI and postoperative FJS and the association between postoperative FJS and preoperative CSI severity were determined. Moreover, difference in each FJS item was evaluated by CSI severity.

Results

Twenty-six patients (9.9%) had central sensitization preoperatively. Preoperative CSI scores and postoperative FJS were negatively correlated (r =  − 0.331, p < 0.0001). The postoperative FJS was significantly lower in patients with moderate or higher preoperative CSI severity than that in patients with subclinical or mild preoperative CSI severity (p < 0.05). FJS items with movement of daily life were significantly worse in the moderate or higher CSI severity compared with subclinical group (p < 0.05 or p < 0.01).

Conclusion

Central sensitization prior to THA negatively related to postoperative FJS. In particular, the relationship of central sensitization was found to be significant in FJS items with movement, which would lead to lower patient satisfaction after THA. To get better postoperative outcomes in patients with preoperative central sensitization, improving central sensitization would be important.
A mHealth intervention to reduce perceived stress in patients with ischemic heart disease: study protocol of the randomized, controlled confirmatory intervention “mStress-IHD” trial
Authors: Lortz Julia , Rassaf Tienush , Jansen Christoph , Knuschke Ramtin , Schweda Adam , Schnaubert Lenka , Rammos Christos , Köberlein-Neu Juliane , Skoda Eva-Maria , Teufel Martin , Bäuerle Alexander
Published: September 2023

Background

Stress is highly prevalent in patients with ischemic heart disease (IHD) and is associated with lower health-related quality of life and impaired cardiovascular outcome. The importance of stress management is now recognized in recent guidelines for the management of cardiovascular disease. However, effective stress management interventions are not implemented in clinical routine yet. The development of easily disseminated eHealth interventions, particularly mHealth, may offer a cost-effective and scalable solution to this problem. The aim of the proposed trial is to assess the efficiency and cost-effectiveness of the mHealth intervention “mindfulHeart” in terms of reducing stress in patients with IHD.

Methods and analysis

This randomized controlled confirmatory interventional trial with two parallel arms has assessments at six measurement time points: baseline (T0, prior randomization), post-treatment (T1), and four follow-ups at months 1, 3, 6, and 12 after intervention (T2, T3, T4, and T5). We will include patients with confirmed diagnosis of IHD, high-perceived stress, and use of an internet-enabled smartphone. Patients will be randomized into two groups (intervention vs. control). The proposed sample size calculation allocates 128 participants in total. The primary analysis will be performed in the intention-to-treat population, with missing data imputed. An ANCOVA with the outcome at T1, a between-subject factor (intervention vs. control), and the participants’ pre-intervention baseline values as a covariate will be used. Different ANOVAs, regression, and descriptive approaches will be performed for secondary analyses.

Ethics

The Ethics Committee of the Medical Faculty of the University of Duisburg-Essen approved the study (22–11,015-BO).

Trial registration

ClinicalTrials NCT05846334. Release 26.04.2023.
Successful management of temporary veno-venous extracorporeal membrane oxygenation for a pediatric lung transplant recipient with bronchiolitis obliterans syndrome awaiting lung re-transplantation: a case report
Authors: Tomioka Yasuaki , Miyoshi Kentaroh , Tanaka Shin , Sugimoto Seiichiro , Kanai Rie , Nikai Tetsuro , Toyooka Shinichi , Yamane Masaomi
Published: September 2023

Background

The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is an uncommon strategy in Japan owing to the severe donor shortage and absence of urgent allocation policy. Moreover, the use of veno-venous (VV) ECMO for immunosuppressed patients is controversial; thus, applying ECMO to patients who await lung re-transplantation is challenging.

Case presentation

A 16-year-old lung transplant recipient with grade 3 bronchiolitis obliterans syndrome was waitlisted for lung re-transplantation. Eleven months later, he fell into severe respiratory acidosis with hypercapnia, which were not resolved with mechanical ventilation. VV ECMO was introduced to minimize lung stress and strain. Tracheostomy was additionally performed on day 5 after the start of ECMO, and respiratory condition swiftly improved; hence, the weaning process from VV ECMO began on day 9. Rehabilitation became implementable, and bilateral re-lung transplantation was successfully performed 6 months after the ECMO treatment. No critical complication related to the precedent use of ECMO was noted.

Conclusions

VV ECMO can be a feasible treatment option even for lung transplant candidates awaiting re-transplantation for a prolonged period. Introduction of ECMO and tracheostomy in the early deterioration stage may be crucial to successful subsequent patient management.
A comparative study of two-sex life table parameters of Orius laevigatus fieber (Hemiptera: anthocoridae) on two mealybug species, Planococcus citri Risso, and P. solenopsis Tinsley (Hemiptera: Pseudococcidae)
Authors: Kahya Dogancan
Published: September 2023

Background

Augmentative biological control is a crucial component of Integrated Pest Management, and Orius laevigatus Fieber (Hemiptera: Anthocoridae) is an important predator used commercially. However, the two-sex life table parameters of O. laevigatus on Planoccocus citri Risso, and P. solenopsis Tinsley (Hemiptera: Pseudococcidae) have not been fully characterised. This study aimed to assess the potential of P. citri and, P. solenopsis as prey for mass-rearing the predatory bug. To accomplish this, three different prey items (individuals of P. citri, P. soleneopsis, and eggs of Ephestia kuehniella Zeller (Lepidoptera: Pyralidae)) were used to determine the life table parameters of the minute pirate bug.

Results

Daily and total fecundity, adult longevity, APOP, TPOP, and pre-adult periods were calculated in this study. The results showed that daily fecundity was 7.4 ± 0.10, 4.41 ± 0.08, 3.47 ± 0.08, and adult longevity was 20.9 ± 0.47, 15.17 ± 0.31, 14.03 ± 0.39 on E. kuehniella, P. solenopsis and P. citri, respectively. Net reproduction rate (R0) was 57.23 ± 11.35, 17.27 ± 3.57, 11.05 ± 2.30, and the intrinsic rate of increase (r) was 0.172 ± 0.009, 0.084 ± 0.006, 0.069 ± 0.006 on E. kuehniella, P. soleneopsis, and P. citri, respectively. Additionally, finite rate of increase (λ), gross reproductive rate (GRR), and mean generation time (T) were calculated on the three tested prey.

Conclusion

Overall, the results showed that eggs of E. kuehniella were the most suitable prey for the mass-rearing of O. laevigatus. Although P. citri and P. solenopsis had worse results than E. kuehniella, P. solenopsis may still have potential, and O. laevigatus could potentially be used against this pest with further studies in laboratory and field conditions.
Classical Hematology Referrals at an National Cancer Institute–Designated Cancer Center: Lessons Learned
Authors: West Chase V. , Butler Matthew J. , Kaur Supreet , Bowhay-Carnes Elizabeth , Karnad Anand B.
Published: September 2023

PURPOSE

To understand the spectrum and volume of classical hematology (CH) referrals to hematology clinics at a National Cancer Institute (NCI)–designated cancer center (CC) to plan for the delivery of effective and equitable care for this population.

METHODS

One referral office at the Academic CC located in Bexar County, TX, handles all adult hematology referrals. From October 1, 2021, to September 30, 2022, all nonmalignant hematology (MH) referrals were triaged daily to define the category of CH problem. Declined referrals (confirmed at triage that no CH problem was evident) are included as part of this analysis. Electronic consultation (opinion rendered without patient seen) at our CC is available and is not part of this analysis.

RESULTS

One thousand nine hundred forty-five CH referrals were received in the 12-month period. Seventy-six referrals (3.9%) were declined. During the study period, there were 2,289 medical oncology referrals and 779 referrals for MH. CH referrals therefore comprise 39% of all hematology-oncology referrals and 71% of all hematology referrals at the CC. Anemia and thrombotic disorders were the most common categories of the accepted CH referrals at 487 (26%) and 393 (21%), respectively. Video visits were used for 447 of all CH referrals (23%), and the rest were in person.

CONCLUSION

Nearly 40% of all referrals to hematology and medical oncology at our NCI-designated CC are for CH. Effective management of the CH population of patients will allow ideal care for CH problems and also allow cancer-focused care to improve.
Healthcare Professionals’ Insights on the Integration of Kinesiologists into Ontario’s Health System
Authors: Auger Leslie E. , Thomas Scott G. , Fischer Steve , Smith Leanne , Armstrong John , Dar Raheel M. , Srbely John
Published: September 2023

Introduction/Purpose

Kinesiologists are well suited to work collaboratively or independently within the health system to improve patient/client care and well-being. This cross-sectional survey explored perceptions of the integration of registered kinesiologists (RKins) into the health system in Ontario.

Methods

RKins (n = 202) and other health professionals (OHP; n = 337), including physicians, physiotherapists, nurse practitioners, etc., participated in an online survey.

Results

RKins reported working in diverse practice environments, and more than half reported receiving patients/clients through referrals. Of the OHP, 37.7% had ongoing professional interactions with RKins and 86.7% reported high satisfaction with these interactions; 32.6% of OHP reported referring patients/clients to RKins, primarily for exercise prescription (86.0%), treatment of clinical conditions (48.8%), and patient education (46.5%). Perceived barriers to referral included lack of awareness of the RKins’ scope of practice (81.0%), inadequate funding for services (67.1%), and low confidence in the clinical competency of RKins (61.8%).

Conclusions

RKins are experts in exercise-based interventions to prevent, treat, and manage many chronic lifestyle-related diseases. Initiatives to increase awareness of the RKins’ scope of practice, clinical competency, and standards of practice and to increase funding for RKin services are important next steps.
Superior mesenteric artery embolism associated with Cisplatin-induced aortic thrombosis
Authors: Aoki Ryo , Kato Shingo , Nakajima Kento , Sakai Jun , Yoshida Kenichi , Masui Hidenori , Ikeda Shin , Yoshigi Jun , Utsunomiya Daisuke
Published: September 2023

Cardiovascular complications of cancer therapy are among the most important factors affecting cancer prognosis. Cisplatin-induced aortic thrombosis is rare but can be life-threatening in the event of peripheral embolism. In this report, we describe a case of superior mesenteric artery (SMA) embolism associated with cisplatin-induced aortic thrombosis. A 66-year-old male, diagnosed with esophageal cancer, initiated systemic chemotherapy with a regimen consisting of 5-fluorouracil and cisplatin, combined with radiotherapy. After 7 days of chemoradiotherapy, the patient developed a floating thrombus in the ascending aorta and an SMA embolism; chemoradiotherapy was then discontinued. Laparoscopy revealed an ischemic small intestine that required resection; intravenous unfractionated heparin was initiated 3 days after. Computed tomography showed disappearance of the floating aortic thrombus and reduce SMA thrombus size. Early detection of cisplatin-induced aortic thrombosis may prevent fatal outcomes in symptomatic peripheral embolisms, such as SMA embolism, considering anticoagulation, and discontinuation of cisplatin-based chemotherapy may cause resolution of thrombus events.
A checklist and some new records on the teuthofauna of Türkiye in the Northeastern Mediterranean Sea
Authors: Salman Alp , Akalın Sencer , Ünlüoğlu Aydın , Aydın Coşkun Menderes
Published: September 2023

The cephalopod species observed in this study were caught during two concurrent projects on the demersal fisheries resources conducted along the coasts of Türkiye in the Northeastern Mediterranean Sea. The samples were collected by a bottom trawl at depths ranging from 50 to 800 meters, following the guidelines set by MEDITS (International Bottom Trawl Survey in the Mediterranean). Through the study, a total of 22 cephalopod species were determined. Among them, Heteroteuthis dispar (Rüppell, 1844), Chiroteuthis veranii (A. Férussac, 1834), Onychoteuthis banksii (Leach, 1817), Octopus salutii Vérany, 1839 are being reported first time in the Mediterranean coasts of Türkiye.
Effect of different hydraulic loading rates on growth of basil (Ocimum basilicum L. ‘Genovese’) in nutrient film technique aquaponics
Authors: Yeşiltaş Murat , Koçer Mehmet Ali Turan , Sevgili Hüseyin , Koru Edis
Published: September 2023

Aquaponics are promising and sustainable technologies consisting of fish-plant-bacteria consortia in the same system, thereby providing an environmentally friendly system by recycling water and nutrients. This study was planned to investigate the influence of varying hydraulic loading rates (HLR) on the growth of basil plant (Ocimum basilicum L. ‘Genovese’) in a low-cost of electricity nutrient film technique aquaponics (NFT) integrated with African catfish (Clarias gariepinus (Burchell)) under the Eastern Mediterranean climate conditions, Antalya, Türkiye. The hydraulic loading rates tested in plant-growing troughs 2, 4, 8, and 12 m3/m2/day. African catfish showed an excellent feed conversion ratio (0.695) over the experiment. There was no statistically significant difference in plant height, number of leaves, and stem diameter for basil plants, but a statistically significant difference was found in plant weight and leaf area. The best plant weight gain was observed in the 4 m3/m2/day group with 23.0±2.5 g mean weight. The optimum HLR for basil production was estimated as 4.41 m3/m2/day based on yield (kg/m2) and energy consumption (KWh/kg basil) in a basil-African catfish integrated NFT aquaponics. The optimum HLR can maximize production without further increase of energy expenditure. Higher HLRs of 4.41 increase energy cost per unit of basil production.