bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaming up to traverse loneliness: a co-creative journey toward a home care work model for supporting social participation among older adults
Authors: Nordin Therese , Coe Anna-Britt , Nilsson Ingeborg
Published: September 2022

Background

Participatory research is particularly suitable in adressing know-do gaps in health systems. There is a disparity between what is known about the benefits of social participation and home care’s responsibility to provide conditions amenable to older adults’ social participation, and what is accomplished in home care practice. Home care workers are a large, low-power group, whose competences should be better harnessed. We carried out a participatory action research (PAR) project with the goal of generating an improved structure for identifying and alleviating loneliness. This article aims to explore the co-creative process of designing a work model that guides home care workers in supporting social participation among older care recipients.

Methods

Multimodal data from 16 PAR workshops with 14 home care workers were described and explored through the ‘recursive PAR process’ and the ‘framework for occupational enablement for change in community practice”.

Results

The PAR process is outlined through the objectives, activities, and work model, as well as enablement strategies employed throughout the PAR process; as are its opportunities, challenges and implications. The work model describes how care workers can act as discoverers of care recipients’ unmet social needs, employ intentional communication, and link to relevant professions or community services to alleviate loneliness among older home care recipients.

Conclusions

This research process included opportunities of collaborating with enthusiastic and competent home care workers, but also challenges of moving between theory and practice and maintaining active participation between workshops. The resulting work model is in step with the requirements of elderly care, is unique in its field and could comprise a first step toward a more systematic approach of assessing and addressing loneliness. The vivid delineation of the PAR process provided in this paper can aid other researchers in navigating participatory research in home care contexts.
Gut symbiotic bacteria are involved in nitrogen recycling in the tephritid fruit fly Bactrocera dorsalis
Authors: Ren Xueming , Cao Shuai , Akami Mazarin , Mansour Abdelaziz , Yang Yishi , Jiang Nan , Wang Haoran , Zhang Guijian , Qi Xuewei , Xu Penghui , Guo Tong , Niu Changying
Published: September 2022

Background

Nitrogen is considered the most limiting nutrient element for herbivorous insects. To alleviate nitrogen limitation, insects have evolved various symbiotically mediated strategies that enable them to colonize nitrogen-poor habitats or exploit nitrogen-poor diets. In frugivorous tephritid larvae developing in fruit pulp under nitrogen stress, it remains largely unknown how nitrogen is obtained and larval development is completed.

Results

In this study, we used metagenomics and metatranscriptomics sequencing technologies as well as in vitro verification tests to uncover the mechanism underlying the nitrogen exploitation in the larvae of Bactrocera dorsalis. Our results showed that nitrogenous waste recycling (NWR) could be successfully driven by symbiotic bacteria, including Enterobacterales, Lactobacillales, Orbales, Pseudomonadales, Flavobacteriales, and Bacteroidales. In this process, urea hydrolysis in the larval gut was mainly mediated by Morganella morganii and Klebsiella oxytoca. In addition, core bacteria mediated essential amino acid (arginine excluded) biosynthesis by ammonium assimilation and transamination.

Conclusions

Symbiotic bacteria contribute to nitrogen transformation in the larvae of B. dorsalis in fruit pulp. Our findings suggest that the pattern of NWR is more likely to be applied by B. dorsalis, and M. morganii, K. oxytoca, and other urease-positive strains play vital roles in hydrolysing nitrogenous waste and providing metabolizable nitrogen for B. dorsalis.
Epigenetic machinery is functionally conserved in cephalopods
Authors: Macchi Filippo , Edsinger Eric , Sadler Kirsten C.
Published: September 2022

Background

Epigenetic regulatory mechanisms are divergent across the animal kingdom, yet these mechanisms are not well studied in non-model organisms. Unique features of cephalopods make them attractive for investigating behavioral, sensory, developmental, and regenerative processes, and recent studies have elucidated novel features of genome organization and gene and transposon regulation in these animals. However, it is not known how epigenetics regulates these interesting cephalopod features. We combined bioinformatic and molecular analysis ofOctopus bimaculoidesto investigate the presence and pattern of DNA methylation and examined the presence of DNA methylation and 3 histone post-translational modifications across tissues of three cephalopod species.

Results

We report a dynamic expression profile of the genes encoding conserved epigenetic regulators, including DNA methylation maintenance factors in octopus tissues. Levels of 5-methyl-cytosine in multiple tissues of octopus, squid, and bobtail squid were lower compared to vertebrates. Whole genome bisulfite sequencing of two regions of the brain and reduced representation bisulfite sequencing from a hatchling ofO. bimaculoidesrevealed that less than 10% of CpGs are methylated in all samples, with a distinct pattern of 5-methyl-cytosine genome distribution characterized by enrichment in the bodies of a subset of 14,000 genes and absence from transposons. Hypermethylated genes have distinct functions and, strikingly, many showed similar expression levels across tissues while hypomethylated genes were silenced or expressed at low levels. Histone marks H3K27me3, H3K9me3, and H3K4me3 were detected at different levels across tissues of all species.

Conclusions

Our results show that the DNA methylation and histone modification epigenetic machinery is conserved in cephalopods, and that, in octopus, 5-methyl-cytosine does not decorate transposable elements, but is enriched on the gene bodies of highly expressed genes and could cooperate with the histone code to regulate tissue-specific gene expression.
Design and construction of 3D printed devices to investigate active and passive bacterial dispersal on hydrated surfaces
Authors: Kuhn Thierry , Buffi Matteo , Bindschedler Saskia , Chain Patrick S. , Gonzalez Diego , Stanley Claire E. , Wick Lukas Y. , Junier Pilar , Richter Xiang-Yi Li
Published: September 2022

Background

To disperse in water-unsaturated environments, such as the soil, bacteria rely on the availability and structure of water films forming on biotic and abiotic surfaces, and, especially, along fungal mycelia. Dispersal along such “fungal highways” may be driven both by mycelial physical properties and by interactions between bacteria and fungi. However, we still do not have a way to disentangle the biotic and abiotic elements.

Results

We designed and 3D printed two devices establishing stable liquid films that support bacteria dispersal in the absence of biotic interactions. The thickness of the liquid film determined the presence of hydraulic flow capable of transporting non-motile cells. In the absence of flow, only motile cells can disperse in the presence of an energy source. Non-motile cells could not disperse autonomously without flow but dispersed as “hitchhikers” when co-inoculated with motile cells.

Conclusions

The 3D printed devices can be used as an abiotic control to study bacterial dispersal on hydrated surfaces, such as plant roots and fungal hyphae networks in the soil. By teasing apart the abiotic and biotic dimensions, these 3D printed devices will stimulate further research on microbial dispersal in soil and other water-unsaturated environments.
Point-of-care viscoelastic coagulation assessment in healthy dogs during the perianesthetic period
Authors: Wang Wen H. , Lynch Alex M. , Balko Julie A. , Duffy Daniel J. , Robertson James B. , Posner Lysa P.
Published: September 2022

Background

The viscoelastic coagulation monitor (VCM Vet) is a novel, portable device that provides a global assessment of hemostasis. The study aims were to evaluate serial viscoelastic analysis during the perianesthetic period in healthy dogs and to compare the agreement between two VCM Vet devices. Twenty healthy dogs undergoing orthopedic surgery were enrolled. Whole blood samples were collected from an intravenous catheter at four time points: baseline, 15 min after premedication, 60 min after inhalant initiation, and 60 min after inhalant termination. Viscoelastic tests were performed in duplicate on different devices, providing: clot time (CT; seconds), clot formation time (CFT; seconds), alpha angle (α; degrees), amplitude (units) at 10 (A10) and 20 (A20) minutes post clot time, maximum clot firmness (MCF; units), and lysis index (%) at 30 (Li30) and 45 (Li45) minutes post maximum clot formation.

Results

One hundred sixty samples were analyzed. The speed of CT and CFT significantly decreased an average of 25.5 s (95% confidence interval [CI]15.9–35.0) and 6.9 s (95% CI 3.1–10.7) per time point, respectively. There were no significant changes in clot strength or lysis variables. The Bland–Altman style plot shows an acceptable rate of agreement for all variables with intra-class correlation ranging from 0.64–0.94.

Conclusion

The rate of clot formation (CT and CFT) decreased over the perianesthetic period in healthy dogs undergoing surgery. These changes were small and occurred without changes in clot strength or fibrinolysis rate, thus were not clinically relevant. There was clinically acceptable consistency between devices.
Measurement of distal intramural spread and the optimal distal resection by naked eyes after neoadjuvant radiation for rectal cancers
Authors: Sun Ge , Ye Xiaolong , Zheng Kuo , Zhang Hang , Broens Paul , Trzpis Monika , Lou Zheng , Gao Xianhua , Liu Lianjie , Hao Liqiang , Furnee Edgar , Bai Chenguang , Zhang Wei
Published: September 2022

Background

The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length.

Methods

Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor’s visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o’clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature.

Results

At the distal 5, 6, and 7 o’clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was − 0.3 (95%CI − 4.0 ~ 3.4) mm, − 0.9 (95%CI − 3.4 ~ 1.7) mm, and − 0.4 (95%CI − 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively.

Conclusions

The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.
An effective method to reduce lymphatic drainage post-lateral cervical lymph node dissection of differentiated thyroid cancer: a retrospective analysis
Authors: Zhang Ming-Liang , Guo Lou-Ming , Li Peng-Cheng , Zhang Jing-Kang , Guo Chen-Xu
Published: September 2022

Background

Lymph or chyle leak (LL/CL) is severe complications after lateral cervical lymph node dissection (LLND), mainly due to iatrogenic injury of the lymphatic duct. Efficient and well-operated methods to reduce postoperative drainage are still lacking. This was a feasibility study to evaluate a new method of preventing LL/CL compared to conventional treatment.

Method

We retrospectively analyzed 20 consecutive patients who used the “pedicled omohyoid flap covering (POFC)” method during LLND from January 2019 to December 2021 in our center as an observation group. Another 20 consecutive patients used the conventional method during LLND in this period as a control group. The clinical and pathological features of the two groups were compared, and the related factors that affected postoperative lymphatic drainage were analyzed with Cox proportional hazards models.

Results

The drainage volume per 24 h and the incidence of LL/CL in the control group were both higher than that in the observation group (all P < 0.05), and the number of lymph nodes dissected in the IV region > 10 and the use of the POFC method were the independent risk factors that significantly affected the incidence of LL/CL post LLND (all P < 0.05).

Conclusions

POFC is a safe and useful method for reducing drainage and preventing LL/CL post-LLND, especially for patients with heavy metastasis of the lymph nodes in the IV region.
H19 may regulate the immune cell infiltration in carcinogenesis of gastric cancer through miR-378a-5p/SERPINH1 signaling
Authors: Li Jianxin , Han Ting , Wang Xin , Wang Yinchun , Chen Xuan , Chen Wangsheng , Yang Qingqiang
Published: September 2022

Background

Increasing studies have indicated that noncoding RNA (ncRNA)-mediated competing endogenous RNA (ceRNA) network serves as a significant role in cancer progression, but the underlying regulatory mechanisms of which in gastric cancer (GC) remain largely unclear.

Methods

Based on Gene Expression Omnibus and The Cancer Genome Atlas datasets, potential biomarkers for GC were screened and validated by machine learning. Then, upstream regulatory ncRNA of potential biomarkers was identified to construct a novel ceRNA network in GC through means of stepwise reverse prediction and validation. Ultimately, tumor immune cell infiltration analysis was performed based on the EPIC algorithm.

Results

A total of 188 differentially expressed genes (DEGs) were screened, and three candidate diagnostic biomarkers (FAP, PSAPL1, and SERPINH1) for GC were identified and validated. Subsequently, H19 and miR-378a-5p were identified as upstream regulatory ncRNAs that could potentially bind SERPINH1 in GC. Moreover, Immune infiltration analysis revealed that each component in the ceRNA network (H19/miR-378a-5p/SERPINH1) was significantly correlated with the infiltration abundances of diverse tumor-infiltrating immune cells.

Conclusions

H19 may regulate the immune cell infiltration in carcinogenesis of GC through miR-378a-5p/SERPINH1 signaling.
Probing spatiotemporal PKA activity at the ryanodine receptor and SERCA2a nanodomains in cardomyocytes
Authors: Xu Bing , Wang Ying , Bahriz Sherif M. F. M. , Zhao Meimi , Zhu Chaoqun , Xiang Yang K.
Published: September 2022

Spatiotemporal regulation of subcellular protein kinase A (PKA) activity for precise substrate phosphorylation is essential for cellular responses to hormonal stimulation. Ryanodine receptor 2 (RyR2) and (sarco)endoplasmic reticulum calcium ATPase 2a (SERCA2a) represent two critical targets of β adrenoceptor (βAR) signaling on the sarcoplasmic reticulum membrane for cardiac excitation and contraction coupling. Using novel biosensors, we show that cardiac β1AR signals to both RyR2 and SERCA2a nanodomains in cardiomyocytes from mice, rats, and rabbits, whereas the β2AR signaling is restricted from these nanodomains. Phosphodiesterase 4 (PDE4) and PDE3 control the baseline PKA activity and prevent β2AR signaling from reaching the RyR2 and SERCA2a nanodomains. Moreover, blocking inhibitory G protein allows β2AR signaling to the RyR2 but not the SERCA2a nanodomains. This study provides evidence for the differential roles of inhibitory G protein and PDEs in controlling the adrenergic subtype signaling at the RyR2 and SERCA2a nanodomains in cardiomyocytes.
Amine-modified nanoplastics promote the procoagulant activation of isolated human red blood cells and thrombus formation in rats
Authors: Kim Eun-Hye , Choi Sungbin , Kim Donghyun , Park Han Jin , Bian Yiying , Choi Sang Ho , Chung Han Young , Bae Ok-Nam
Published: September 2022

Background

Microplastics (MPs) and nanoplastics (NPs) formed from decomposed plastic are increasing environmental threats. Although MPs and NPs exposed through various routes enter the systemic circulation, the potential toxicity of those is largely unknown. We investigated whether polystyrene NPs (PS-NPs) promote the coagulation activity of red blood cells (RBCs).

Results

We tested several types of PS-NPs using human RBCs and found that amine-modified 100 nm PS-NPs were the most potent. We measured the uptake of PS-NPs using flow cytometry and confocal microscopy. Electron microscopy revealed morphological changes of RBCs by PS-NPs. PS-NPs induced the externalization of phosphatidylserine, generation of microvesicles in RBCs, and perturbations in the intracellular microenvironment. PS-NPs increased the activity of scramblases responsible for phospholipid translocation in RBCs. PS-NPs modulated the functional interaction to adjacent tissues and coagulation cascade, enhancing RBC adhesion and thrombin generation. Our observations in human RBCs were consistent with those in isolated rat RBCs, showing no inter-species differences. In rat venous thrombosis models, the intravenous administration of PS-NPs enhanced thrombus formation.

Conclusion

Amine-modified PS-NPs induce the prothrombotic activation of RBCs causing thrombus formation. We believe that our study will contribute to understanding the potential toxicity of amine-modified polystyrene particles in blood cells and cardiovascular systems.
Effect of dorsal nerve fascial island flap on repairing distal soft tissue defects at the proximal segment of the index, middle, ring, and little fingers
Authors: Wang Xun , Lv Jingdan , Liu Shujiao , Xu Shuangyue , Yan Guoliang
Published: September 2022

Background

To investigate the effect of the dorsal nerve fascial island (DNFI) flap on repairing finger soft tissue defects at the distal segments.

Methods

Fifty patients with distal soft tissue defects at the index, middle, ring, or little fingers were treated with a DNFI flap at the proximal phalanx between February 2008 and May 2018. The nutrient vascular chain around the dorsal branch of the proper palmar digital nerves served as the flap axis. The dorsal branch of the proper palmar digital arteries provided blood supply. The fascia pedicle served as the venous system. All patients were followed for 6 months.

Results

All 50 flaps survived. The appearance, color, and texture of the skin returned to normal. The sensory function was partially restored. The two-point discrimination of the finger flap was 7–10 mm.

Conclusions

The DNFI flap at the proximal phalanges of the index, middle, ring, and little fingers is an effective surgical option. The technique has a high flap survival rate and long pedicle, which can repair different parts of the finger. The flap also restores the sensory function of the finger without damaging the main nerves or blood vessels. The flap treatment is an optimal option for finger soft tissue defects at the distal segments.
Radiomics analysis using MR imaging of subchondral bone for identification of knee osteoarthritis
Authors: Xue Zhihao , Wang Liao , Sun Qi , Xu Jia , Liu Ying , Ai Songtao , Zhang Lichi , Liu Chenglei
Published: September 2022

Background

To develop a magnetic resonance imaging (MRI)-based radiomics predictive model for the identification of knee osteoarthritis (OA), based on the tibial and femoral subchondral bone, and compare with the trabecular structural parameter-based model.

Methods

Eighty-eight consecutive knees were scanned with 3T MRI and scored using MRI osteoarthritis Knee Scores (MOAKS), in which 56 knees were diagnosed to have OA. The modality of sagittal three-dimensional balanced fast-field echo sequence (3D BFFE) was used to image the subchondral bone. Four trabecular structural parameters (bone volume fraction [BV/TV], trabecular thickness [Tb.Th], trabecular separation [Tb.Sp], and trabecular number) and 93 radiomics features were extracted from four regions of the lateral and medial aspects of the femur condyle and tibial plateau. Least absolute shrinkage and selection operator (LASSO) was used for feature selection. Machine learning-based support vector machine models were constructed to identify knee OA. The performance of the models was assessed by area under the curve (AUC) of the receiver operator characteristic (ROC). The correlation between radiomics features and trabecular structural parameters was analyzed using Pearson’s correlation coefficient.

Results

Our radiomics-based classification model achieved the AUC score of 0.961 (95% confidence interval [CI], 0.912–1.000) when distinguishing between normal and knee OA, which was higher than that of the trabecular parameter-based model (AUC, 0.873; 95% CI, 0.788–0.957). The first-order, texture, and Laplacian of Gaussian-based radiomics features correlated positively with Tb.Th and BV/TV, but negatively with Tb.Sp (P < 0.05).

Conclusions

Our results suggested that our MRI-based radiomics models can be used as biomarkers for the classification of OA and are superior to the conventional structural parameter-based model.
Rare clinical phenotype of filaminopathy presenting as restrictive cardiomyopathy and myopathy in childhood
Authors: Muravyev A. , Vershinina T. , Tesner P. , Sjoberg G. , Fomicheva Yu. , Čajbiková N. Novák , Kozyreva A. , Zhuk S. , Mamaeva E. , Tarnovskaya S. , Jornholt J. , Sokolnikova P. , Pervunina T. , Vasichkina E. , Sejersen T. , Kostareva A.
Published: September 2022

Background

FLNC is one of the few genes associated with all types of cardiomyopathies, but it also underlies neuromuscular phenotype. The combination of concomitant neuromuscular and cardiac involvement is not often observed in filaminopathies and the impact of this on the disease prognosis has hitherto not been analyzed.

Results

Here we provide a detailed clinical, genetic, and structural prediction analysis of distinct FLNC-associated phenotypes based on twelve pediatric cases. They include early-onset restrictive cardiomyopathy (RCM) in association with congenital myopathy. In all patients the initial diagnosis was established during the first year of life and in five out of twelve (41.7%) patients the first symptoms were observed at birth. RCM was present in all patients, often in combination with septal defects. No ventricular arrhythmias were noted in any of the patients presented here. Myopathy was confirmed by neurological examination, electromyography, and morphological studies. Arthrogryposes was diagnosed in six patients and remained clinically meaningful with increasing age in three of them. One patient underwent successful heart transplantation at the age of 18 years and two patients are currently included in the waiting list for heart transplantation. Two died due to congestive heart failure. One patient had ICD instally as primary prevention of SCD. In ten out of twelve patients the disease was associated with missense variants and only in two cases loss of function variants were detected. In half of the described cases, an amino acid substitution A1186V, altering the structure of IgFLNc10, was found.

Conclusions

The present description of twelve cases of early-onset restrictive cardiomyopathy with congenital myopathy and FLNC mutation, underlines a distinct unique phenotype that can be suggested as a separate clinical form of filaminopathies. Amino acid substitution A1186V, which was observed in half of the cases, defines a mutational hotspot for the reported combination of myopathy and cardiomyopathy. Several independent molecular mechanisms of FLNC mutations linked to filamin structure and function can explain the broad spectrum of FLNC-associated phenotypes. Early disease presentation and unfavorable prognosis of heart failure demanding heart transplantation make awareness of this clinical form of filaminopathy of great clinical importance.
Identifying project topics and requirements in a citizen science project in rare diseases: a participative study
Authors: Neff Michaela , Storf Holger , Vasseur Jessica , Scheidt Jörg , Zerr Thomas , Khouri Andreas , Schaaf Jannik
Published: September 2022

Background

Due to their low prevalence (< 5 in 10,000), rare diseases are an important area of research, with the active participation of those affected being a key factor. In the Citizen Science project “SelEe” (Researching rare diseases in a citizen science approach), citizens collaborate with researchers using a digital application, developed as part of the project together with those affected, to answer research questions on rare diseases. The aim of this study was to define the rare diseases to be considered, the project topics and the initial requirements for the implementation in a digital application.

Methods

To address our research questions, we took several steps to engage citizens, especially those affected by rare diseases. This approach included the following methods: pre- and post-survey (questionnaire), two workshops with focus group discussion and a requirements analysis workshop (with user stories).

Results

In the pre-survey, citizens suggested 45 different rare diseases and many different disease groups to be considered in the project. Two main project topics (A) “Patient-guided documentation and data collection” (20 votes) and (B) “Exchange of experience and networking” (13 votes) were identified as priorities in the workshops and ranked in the post-survey. The requirements workshop resulted in ten user stories and six initial requirements to be implemented in the digital application.

Conclusion

Qualitative, citizen science research can be used to collectively identify stakeholder needs, project topics and requirements for a digital application in specific areas, such as rare diseases.
Comprehensive and scalable quantification of splicing differences with MntJULiP
Authors: Yang Guangyu , Sabunciyan Sarven , Florea Liliana
Published: September 2022

Tools for differential splicing detection have failed to provide a comprehensive and consistent view of splicing variation. We present MntJULiP, a novel method for comprehensive and accurate quantification of splicing differences between two or more conditions. MntJULiP detects both changes in intron splicing ratios and changes in absolute splicing levels with high accuracy, and can find classes of variation overlooked by other tools. MntJULiP identifies over 29,000 differentially spliced introns in 1398 GTEx brain samples, including 11,242 novel introns discovered in this dataset. Highly scalable, MntJULiP can process thousands of samples within hours to reveal splicing constituents of phenotypic differentiation.
PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO)
Authors: Kim Eun Kyoung , Choi Hong-Mi , Choi Eui-Young , Lee Hye Sun , Park Goeun , Han Dong Woo , Lee Sang-Eun , Park Chan Seok , Hwang Ji-won , Choi Jae Hyuk , Kim Mi-Na , Kim Hyung-Kwan , Kim Dae-Hee , Shin Sung-Hee , Sohn Il Suk , Shin Mi-Seung , Na Jin Oh , Cho Iksung , Lee Sun Hwa , Park Yong Hyun , Park Tae-Ho , Kim Kye Hun , Cho Goo-Young , Jung Hae Ok , Park Dae-Gyun , Hong Ji Yeon , Kang Duk-Hyun
Published: September 2022

Background

Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery.

Methods

This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery.

Discussion

This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs.

Trial registration

The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.
Perioperative statin medication impairs pulmonary outcome after abdomino-thoracic esophagectomy
Authors: Reichert Martin , Lang Maike , Pons-Kühnemann Joern , Sander Michael , Padberg Winfried , Hecker Andreas
Published: September 2022

Background

Although surgery is the curative option of choice for patients with locally advanced esophageal cancer, morbidity, especially the rate of pulmonary complications, and consequently mortality of patients undergoing abdomino-thoracic esophagectomy remain unacceptably high. Causes for developing post-esophagectomy pulmonary complications are trauma to the lung and thoracic cavity as well as systemic inflammatory response. Statins are known to influence inflammatory pathways, but whether perioperative statin medication impacts on inflammatory response and pulmonary complication development after esophagectomy had not been investigated, yet.

Methods

Retrospective analysis and propensity score matching of patients, who either received perioperative statin medication [statin( +)] or not [statin( −)], with regard to respiratory impairment (PaO2/FiO2 < 300 mmHg), pneumonia development, and inflammatory serum markers after abdomino-thoracic esophagectomy.

Results

Seventy-eight patients who underwent abdomino-thoracic esophagectomy for cancer were included into propensity score pair-matched analysis [statin( +): n = 26 and statin( −): n = 52]. Although no differences were seen in postoperative inflammatory serum markers, C-reactive protein values correlated significantly with the development of pneumonia beyond postoperative day 3 in statin( −) patients. This effect was attenuated under statin medication. No difference was seen in cumulative incidences of respiratory impairment; however, significantly higher rate (65.4% versus 38.5%, p = 0.0317, OR 3.022, 95% CI 1.165–7.892) and higher cumulative incidence (p = 0.0468) of postoperative pneumonia were seen in statin( +) patients, resulting in slightly longer postoperative stay on intensive care unit (p = 0.0612) as well as significantly prolonged postoperative in-hospital stay (p = 0.0185).

Conclusions

Development of pulmonary complications after abdomino-thoracic esophagectomy is multifactorial but frequent. The establishment of preventive measures into the perioperative clinical routine is mandatory for an improved patient outcome. Perioperative medication with statins might influence pneumonia development in the highly vulnerable lung after abdomino-thoracic esophagectomy. Perioperative interruption of statin medication might be beneficial in appropriate patients; however, further clinical trials and translational studies are needed to prove this hypothesis.
Travel related histoplasmosis – a diagnostic challenge in a patient with tumor necrosis factor alpha (TNF-α) inhibitor therapy
Authors: Hofmann Eveline , Mühlethaler Konrad , Pollak Matthias , Ott Daniel , Bienz Nora , Zimmerli Stefan , Hirzel Cédric
Published: September 2022

Introduction

In a non-endemic setting, disseminated histoplasmosis is a rare travel-related health problem of immunosuppressed returnees from endemic regions.

Methods

We describe the case of a 68-year-old man with rheumatoid arthritis and tumor necrosis factor alpha (TNF-α) inhibitor treatment-related immunodeficiency, who suffered from disseminated histoplasmosis after traveling to Brazil. Based on this case, we discuss challenges and pitfalls associated with the diagnosis of disseminated histoplasmosis in a non-endemic setting.

Results

The disease mimicked a hemophagocytic lymphohistiocytosis (HLH) like syndrome. Histoplasma capsulatum was microscopically detected in bronchoalveolar fluid and bone marrow aspirate smears, but was initially misclassified as Leishmania spp., another class of pathogens, which may cause HLH like syndromes in immunocompromised individuals.

Discussion

Since the clinical symptoms of histoplasmosis are nonspecific and physicians in non-endemic regions might not be familiar with this disease pattern, there is a risk of delayed diagnosis of travel related cases. Taking a thorough travel history is key in unclear cases of illness in immunocompromised patients.
A feasibility study of a randomized controlled trial protocol to assess the impact of an eHealth intervention on the provision of dietary advice in primary care
Authors: Jefferson Katherine , Ward Michael , Pang Wei-Hsi , Arcand JoAnne
Published: September 2022

Background

Canadian sodium intakes remain high despite population-wide sodium reduction initiatives, highlighting the need for personal action in reducing dietary sodium. eHealth interventions support patients in dietary change and assist clinicians in decision-making and delivering care, including provision of advice. To date, impact of diet-focused eHealth tools, like the Sodium Calculator (SC) dietary screening tool, on clinical outcomes has received minimal examination. This study assessed feasibility of a randomized controlled trial (RCT) protocol to examine the impact of the SC, a physician-focused intervention, on the quality of dietary sodium reduction advice provided by physicians to their patients with hypertension.

Methods

Primary care physicians from community-based primary care clinics were randomized to one of two groups: (1) ‘usual care’ for dietary sodium counselling or (2) dietary sodium counselling using the SC (‘experimental group’). The primary endpoint was protocol feasibility defined by the following outcomes: process (e.g. recruitment, retention, protocol adherence, acceptability of intervention), resources (e.g. needs, impact on workflow), and management (e.g. staff requirements). Outcomes were assessed using direct observation, interviews, and questionnaires with patients, physicians, and clinic staff.

Results

Seven physicians (n = 4 in experimental group, n = 3 in usual care group) and 65 patients with hypertension (48.5% men, 69.8 ± 10.1 years) successfully participated. The main challenges identified is related to recruitment rate (48% for patients, 20% for physicians) and physician protocol adherence (76%). These improved with minor protocol modifications. There were several areas of protocol success such as no disruption to physician workflow, hiring clinic nurses as research staff, having a physician site lead to support physician recruitment, and a ‘Protocol Prompt Form’ to increase physician protocol adherence. Importantly, there was a high degree of acceptability of the SC intervention among experimental group physicians [n = 3 (75%)].

Conclusions

The modified RCT protocol was considered feasible. The identified successes can be leveraged, and the risks can be mitigated, during implementation of a full-scale RCT. Assessment of this RCT protocol is an important step in understanding the effectiveness of diet-focused eHealth tools to supporting physician self-efficacy in assessing, monitoring, and implementing dietary advice in routine clinical practice and supporting patients in effective behaviour change.
Practice Patterns and Perspectives on Stereotactic Body Radiation Therapy for the Metastatic Spine From Lower- and Middle-Income Countries
Authors: Pathak Rima Sanjay , Tibdewal Anil , Kinhikar Rajesh , Wakeham Katherine , Akbarov Kamal , Cordero Lisbeth , Khandavalli Ashwini , Agarwal Jai Prakash
Published: September 2022

PURPOSE

We wanted to understand the current practice patterns and stereotactic body radiation therapy (SBRT) utilization for spine metastases in lower- and middle-income countries (LMICs).

METHODS

A questionnaire was designed to identify the current practice patterns of treating spine metastases, uptake of spine SBRT in routine care, dose fractionations commonly used, and the perceived benefits and toxicities of using ablative doses. Individuals registering for a spine SBRT workshop were requested to answer the questionnaire.

RESULTS

We received 395 responses from radiation oncologists (ROs) working in 12 different LMICs. The majority of respondents were from an academic institute (57.5%). Two hundred seventy-four respondents further identified themselves from the government/public sector (44.89%), corporate/private sector (47.89%), not-for-profit organization (5.4%), or public-private partnership (5.4%). The respondents indicated that 8.43%, 27.46%, 41.73%, and 10.04% of the spine metastases patients are treated using clinical marking, X-ray–based, 3D conformal radiation therapy, and SBRT, respectively. A third of the respondents did not have any experience of spine SBRT; those with high-volume practice were predominantly from an academic institute. The majority of respondents would use spine SBRT to reduce pain severity (71.9%) and achieve durable pain control (61.01%) in the setting of oligometastases (92.73%) and reirradiation (56.69%). Respondents preferred 3- to 5-fraction regimens (64.9%) over 1-2 fractions (33.68%). The top three reasons for not using spine SBRT were resource constraints (50%), lack of machine (37.11%), and lack of training (27.34%).

CONCLUSION

There is heterogeneity in spine SBRT practice and utilization between academic and nonacademic institutes. Resource and infrastructure constraints along with lack of training are limiting the use of SBRT among ROs from LMICs. Collaborative studies from LMICs will help in resolving unique challenges posed by resource constraints.
Molecular Tumor Board–Assisted Care in an Advanced Cancer Population: Results of a Phase II Clinical Trial
Authors: Miller Rachel W. , Hutchcraft Megan L. , Weiss Heidi L. , Wu Jianrong , Wang Chi , Liu Jinpeng , Jayswal Rani , Buchanan Mikayla , Anderson Abigail , Allison Derek B. , El Khouli Riham H. , Patel Reema A. , Villano John L. , Arnold Susanne M. , Kolesar Jill M.
Published: September 2022

PURPOSE

Multidisciplinary molecular tumor boards (MTBs) interpret next-generation sequencing reports and help oncologists determine best therapeutic options; however, there is a paucity of data regarding their clinical utility. The purpose of this study was to determine if MTB-directed therapy improves progression-free survival (PFS) over immediately prior therapy in patients with advanced cancer.

METHODS

This single-arm, prospective phase II clinical trial enrolled patients with advanced cancer with an actionable mutation who received MTB-recommended targeted therapy between January 1, 2017, and October 31, 2020. MTB-recommended both on-label (level 1 evidence) and off-label (evidence levels 2 and 3) therapies. Of the 93 enrolled patients, 43 were treated frontline and 50 received second-line or greater-line therapy. The primary outcome was the probability of patients treated with second-line or greater-line MTB-directed therapy who achieved a PFS ratio ≥ 1.3 (PFS on MTB-directed therapy divided by PFS on the patient's immediately prior therapy). Secondary outcomes included PFS for patients treated frontline and overall survival and adverse effects for the entire study population.

RESULTS

The most common disease sites were lung (35 of 93, 38%), gynecologic (17 of 93, 18%), GI (16 of 93, 17%), and head and neck (7 of 93, 8%). The Kaplan-Meier estimate of the probability of PFS ratio ≥ 1.3 was 0.59 (95% CI, 0.47 to 0.75) for patients treated with second-line or greater-line MTB-directed therapy. The median PFS was 449 (range 42-1,125) days for patients treated frontline. The median overall survival was 768 (range 22-1,240) days. There were four nontreatment-related deaths.

CONCLUSION

When treated with MTB-directed therapy, most patients experienced improved PFS compared with immediately prior treatment. MTB-directed targeted therapy may be a strategy to improve outcomes for patients with advanced cancer.
Advances on the roles of tenascin-C in cancer
Authors: Yilmaz Alev , Loustau Thomas , Salomé Nathalie , Poilil Surendran Suchithra , Li Chengbei , Tucker Richard P. , Izzi Valerio , Lamba Rijuta , Koch Manuel , Orend Gertraud
Published: September 2022

The roles of the extracellular matrix molecule tenascin-C (TNC) in health and disease have been extensively reviewed since its discovery over 40 years ago. Here, we will describe recent insights into the roles of TNC in tumorigenesis, angiogenesis, immunity and metastasis. In addition to high levels of expression in tumors, and during chronic inflammation, and bacterial and viral infection, TNC is also expressed in lymphoid organs. This supports potential roles for TNC in immunity control. Advances using murine models with engineered TNC levels were instrumental in the discovery of important functions of TNC as a danger-associated molecular pattern (DAMP) molecule in tissue repair and revealed multiple TNC actions in tumor progression. TNC acts through distinct mechanisms on many different cell types with immune cells coming into focus as important targets of TNC in cancer. We will describe how this knowledge could be exploited for cancer disease management, in particular for immune (checkpoint) therapies.
Development of a combined surface plasmon resonance and love wave-surface acoustic wave system for biophysical studies
Authors: Σαμαρέντσης Αναστάσιος
Published: September 2022

Ο τομέας των βιοαισθητήρων είναι στενά συνδεδεμένος με την ανάπτυξη ευαίσθητων αναλυτικών τεχνικών. Οι βιοαισθητήρες μπορούν να οριστούν ως αναλυτικές συσκευές, που ενσωματώνουν ένα βιολογικό στοιχείο αναγνώρισης και έναν φυσικό μετατροπέα με σκοπό την ανίχνευση ενός συγκεκριμένου βιολογικού μορίου-στόχου. Παρά την σημαντική πρόοδο στον τομέα, εξακολουθεί να υπάρχει έντονη ζήτηση για την ανάπτυξη καινοτόμων συστημάτων που θα παρέχουν περισσότερες και πιο ακριβείς αναλυτικές πληροφορίες. Σε αυτήν την διδακτορική διατριβή παρουσιάζουμε την ανάπτυξη ενός καινοτόμου συστήματος που συνδυάζει τις τεχνικές συντονισμού επιφανειακών πλασμονίων (SPR) και επιφανειακών ακουστικών κυμάτων τύπου Love (LW-SAW) σε μία ενιαία πλατφόρμα και την εφαρμογή της σε βιοφυσικές μελέτες. Για να επιτύχουμε τα παραπάνω, πρώτα ερευνήσαμε τις πειραματικές παραμέτρους που απαιτούνται για την αποτελεσματική σύζευξη των δύο τεχνικών. Συγκεκριμένα, σχεδιάστηκε και κατασκευάστηκε ένας υβριδικός βιοαισθητήρας SPR/LW-SAW που ενσωματώνει ένα στρώμα ακουστικού κυματοδηγού, από πολυμερές PMMA, και ένα στρώμα ανίχνευσης με επικάλυψη χρυσού. Ο αισθητήρας αξιολογήθηκε ως προς τα υλικά και τις δομές προκειμένου να προσδιοριστεί το βέλτιστο πάχος των παραπάνω στρωμάτων. Επιπλέον, αναπτύχθηκε ένα σύστημα ροής που αποτελείται από μια πλαστική θήκη τρισδιάστατης-εκτύπωσης ενσωματωμένη με μία κυψελίδα μικρο-ροής, από υλικό PDMS, για να επιτρέπει πειράματα υπό συνεχή ροή. Το σύστημα βαθμονομήθηκε σε μια συστηματική μελέτη των οπτικών και ακουστικών αποκρίσεων κατά την εναπόθεση αυξανόμενη μάζας μετάλλου και κατά την εναλλαγή διαλυμάτων γλυκερόλης και σουκρόζης διαφορετικού ιξώδους. Στην συνέχεια, η ολοκληρωμένη πλατφόρμα SPR/LW-SAW χρησιμοποιήθηκε για τη μελέτη της προσρόφησης πρωτεϊνών σε επιφάνεια χρυσού. Οι πρωτεΐνες που δοκιμάστηκαν περιλαμβάνουν την αλβουμίνη βόειου ορού (BSA) και τρεις πρωτεΐνες που δεσμεύουν τηv βιοτίνη, συγκεκριμένα την αβιδίνη (Av), την στρεπταβιδίνη (SAv) και την νιουτραβιδίνη (NAv). Αποδείξαμε ότι μέσω της κατάλληλης ποσοτικοποίησης των δεδομένων, είναι εφικτό να εξαχθούν ιδιότητες των στρωμάτων πρωτεϊνών που δεν είναι προσβάσιμες με μία μόνο τεχνική. Τέλος, το σύστημα εφαρμόστηκε για τον χαρακτηρισμό μορίων δίκλωνου DNA (dsDNAs) διαφόρων μεγεθών, ακινητοποιημένων στην επιφάνεια μέσω του συμπλόκου στρεπταβιδίνης-βιοτίνης. Τα ακουστικά και οπτικά σήματα αναλύθηκαν με σκοπό να προκύψουν περαιτέρω πληροφορίες για τις ιδιότητες των μορίων DNA, συμπεριλαμβανομένης της μάζας στην επιφάνεια, της διαμόρφωσης τους και της περιεκτικότητας σε νερό. Έχοντας επαληθεύσει τα προαναφερθέντα χαρακτηριστικά, πιστεύουμε ότι το συγκεκριμένο σύστημα θα μπορούσε να βοηθήσει σημαντικά στην μελέτη και ανάλυση βιο-μοριακών αλληλεπιδράσεων σε επιφάνειες.