bluuebunny/crossref_metadata_2025 huggingface dataset:
How familiar are German dermatologists with placebo and nocebo effects and to what extent are these targeted in clinical practice: A survey within the dermatological community
Authors: Krefting Frederik , Hölsken Stefanie , Benson Sven , Schedlowski Manfred , Sondermann Wiebke
Published: June 2023

Background

Every medical treatment inevitably comprises not only physiological, but also psychological components, reflected by placebo and nocebo effects, which significantly affect treatment outcome. However, the extent of knowledge on the mechanisms steering placebo and nocebo effects in the dermatological community in Germany is currently unclear.

Objectives

To assess the state of knowledge about placebo and nocebo effects in the German dermatological community, to evaluate whether this knowledge is already being used in clinical practice, and to investigate whether German dermatologists are interested in learning more about the topic.

Methods

German Dermatologists, the majority working in their own practice, were asked to fill in an online survey addressing the knowledge about placebo and nocebo effects and the feasibility of special techniques to enhance placebo and minimize nocebo effects within the clinical routine.

Results

N = 154 complete (79%) or partial (21%) responses to the survey were recorded in the online database and included in the analysis. All participants reported to know what the placebo effect is and 59.7% (74/124) indicated that they already had experience with prescribing or recommending a treatment without active substances. In contrast, only 62.0% (80/129) stated to know what the nocebo effect is. Participants showed a rather superficial knowledge regarding placebo and nocebo mechanisms. The majority of participants (76.7%, 99/129) expressed their willingness to be further educated about the underlying mechanisms mediating placebo and nocebo effects and the possible application in clinical practice.

Conclusions

The current survey offers a so far unique insight into the state of knowledge of German dermatologists on placebo and nocebo effects. The results indicate a need for education about this topic. Encouragingly, however, German dermatologists considered communication strategies to maximize placebo and reduce nocebo effects and expressed motivation to be trained to implement these strategies in everyday clinical practice.
The invasive twospot livebearer's biology, and its current and potential global distribution
Authors: Gomez‐Maldonado Sebastian , Calleros Adrian , Salazar‐Rueda Isabel , Camacho‐Cervantes Morelia
Published: June 2023

Poeciliids are widely recognized as successful invaders, possessing traits associated with invasion success. Native to Central America and south‐eastern Mexico, the twospot livebearer (Pseudoxiphophorus bimaculatus) is a species recently recognized as invasive in both Central and northern Mexico. Despite its invasive status, limited research exists on its invasion process and the potential threats it poses to native species. In this study, we conducted a comprehensive review of the current knowledge on the twospot livebearer and mapped its current and potential distribution worldwide. The twospot livebearer shares similar traits with other successful invaders within the same family. Notably, it exhibits high fecundity throughout the year and demonstrates resilience to highly polluted and oxygen‐deprived water conditions. This fish serves as a host for several parasites, including generalists, and has been extensively translocated for commercial purposes. Recently, it has also been used for biocontrol within its native range. Apart from existing outside its native range, the twospot livebearer, under current climate conditions and if transported there, could readily colonize biodiversity hotspots in tropical zones worldwide, including the Caribbean Islands, the Horn of Africa, North of Madagascar Island, south‐eastern Brazil, and others located in southern and eastern Asia. Given that this fish is highly plastic and our Species Distribution Model, we consider that all areas with a habitat suitability >0.2 should prevent its arrival and establishment. Our findings underscore the urgent need to recognize this species as a threat to freshwater native topminnows and prevent its introduction and spread.
Microneedle fractional radiofrequency in the treatment of periorbital dark circles
Authors: Nilforoushzadeh Mohammad Ali , Heidari‐Kharaji Maryam , Shahverdi Mohammadhasan , Nouri Maryam , Enamzadeh Rozhin , Nobari Niloufar Najar , Fakhim Tannaz , Rafiee Shohreh
Published: June 2023

Background

Periorbital hyperpigmentation (POH) is a common disorder in the patients. Women are more upset with POH in compare to males. Several methods have been used to the POH, with different efficacy and adverse reactions.

Aim

The aim of the present study is to evaluate the efficacy of microneedle fractional radiofrequency (MRF) in treating POH.

Methods

So, nine patients with POH and the age range of 25–57 years, were treated by microneedle fractional radiofrequency (MRF). The outcome was evaluated via biometric assessment. The colorimeter was used to assess the skin lightness. Mexameter was used for evaluated the amount of Melanin in the periorbital skin. Cutometer was used for skin elasticity assessment. The skin ultrasound imaging system was utilized to estimate the epidermis and dermis diameter and density. Furthermore, Visioface was applied to assessed the skin color and wrinkles. Also patient's satisfaction and physician's assessment were evaluated.

Results

The results displayed that the periorbital skin lightness 32.38% ± 5.67 and elasticity of the R2: 40.29% ± 8.18, R5: 39.03 ± 5.38 and R7: 42.03% ± 14.16 were significantly improved after treatment (p < 0.05). Also the melanin content of the skin was decreased (49.41% ± 9.12). The skin layers were denser in the dermis and also in the epidermis (skin density: 30.21% ± 10.16 and skin thickness: 41.12% ± 13.21) (p < 0.05). The results revealed the decrease in the percent change of the skin color (30.34% ± 9.30) and wrinkle (area: 25.84% ± 6.43 and volume: 30.66% ± 8.12) (p < 0.05). Similarly, the physician and patient's assessment were confirmed the obtained outcomes.

Conclusion

In conclusion, the microneedle RF technique is practicable, effective and safe method for periorbital dark circles treatment.
Sexual well‐being needs of patients with chronic illness expressed in health care: A scoping review
Authors: Igerc Irina , Schrems Berta
Published: June 2023

Aims

To systematically identify and summarize the needs of chronically ill people concerning their sexual well‐being in peer‐reviewed published literature, to enable healthcare professionals to provide support in self‐management satisfying the needs.

Design

A scoping review was performed according to the framework of (JBI Manual for Evidence Synthesis. JBI Global Wiki, 2020). Findings are reported in line with the PRISMA extension for scoping reviews.

Review Methods

A literature search and thematic analysis were conducted.

Data Sources

Full research was carried out in 2022 in the search engine BASE and the following databases: Scopus, MEDLINE, Science Citation Index Expanded, Social Sciences Citation Index and CINAHL. Peer‐reviewed articles published after 2011 were included.

Results

Fifty articles could be found. Seven categories of needs could be identified. People with chronic diseases want their providers to initiate discussions about sexual concerns and treat them trustfully and respectfully. Most of the patients would like the issue of sexuality to be included in routine care. They perceive their medical specialists and psychologists as preferred providers to talk to about this issue. Nurses are seen as primary contact persons but in a smaller number of studies.

Conclusion

Although the scoping review included different types of chronic diseases, the needs of chronically ill patients concerning their sexual well‐being are not very different. Healthcare professionals, especially nurses, who are often the first point of contact for people with chronic illnesses, should take the initiative for open discussions about sexual issues. That requires a new understanding of the role of nurses, training and further education.

Implications for the Profession and/or Patient Care

Providing patient education and facilitating an open discussion about sexuality require further training in the new understanding of the role of the nurse and the concept of sexual well‐being.

Impact

What problem did the study address? Chronic diseases have an impact on patients' sexuality. Patients want to be informed about sexual issues, but providers often do not address them. What were the main findings? Patients with a chronic condition expect providers to initiate discussions about sexual well‐being, regardless of the type of chronic disease. Where and on whom will the research have an impact? The research will impact healthcare professionals', especially nurses', future educational standards and ultimately patients.

Reporting Method

PRISMA extension for scoping reviews.

No patient or public contribution

Not required as it was a literary work (scoping review).
Diurnal changes in apoplast bypass flow of water and ions in salt‐stressed wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.)
Authors: Lu Yingying , Fricke Wieland
Published: June 2023

The aim of the present study was to quantify the contribution of apoplastic bypass flow to the uptake of water and salt across the root cylinder of wheat and barley during day and night. Plants were grown on hydroponics until they were 14–17 days old and then analysed over a single day (16 h) or night (8 h) period while being exposed to different concentrations of NaCl (50, 100, 150 and 200 mM NaCl). Exposure to salt started just before the experiment (short‐term stress) or had started 6d before (longer‐term stress). Bypass flow was quantified using the apoplastic tracer dye 8‐hydroxy‐1,3,6‐pyrenesulphonic acid (PTS). The percent contribution of bypass flow to root water uptake increased in response to salt stress and during the night and amounted to up to 4.4%. Bypass flow across the root cylinder of Na+ and Cl− made up 2%–12% of the net delivery of these ions to the shoot; this percentage changed little (wheat) or decreased (barley) during the night. Changes in the contribution of bypass flow to the net uptake of water, Na+ and Cl− in response to salt stress and day/night are the combined result of changes in xylem tension, the contribution of alternative cell‐to‐cell flow path and the requirement to generate xylem osmotic pressure.
Consumption risk‐sharing under terror shocks: Evidence from value‐chain network rosters in Nigeria
Authors: Chuku Chuku , Ubabukoh Chisom
Published: June 2023

Households in Nigeria live in inherently risky environments; accentuated by the preponderance of terror incidences, banditry, and farmer–herder‐related clashes that are more concentrated in the northern than southern parts of the country. This study examines the proposition that households with a robust network roster—especially networks related to ethnicities and financial remittances from outside their communities—are better able to weather the idiosyncratic and aggregate impact of terror‐related shocks; and thus, experience less consumption variability to terror‐related shock than other similar households without the “insurance” of an external network. Our main empirical strategy applies a panel difference‐in‐differences specification to three waves of the LSMS‐ISA surveys for Nigeria. The results from the study indicate that having external networks outside the community is an important coping mechanism for terror‐related shocks, both for overall welfare and food consumption. The difference in consumption variability between groups with outside network “insurance” and those without could be as high as 20 percentage points. Thus, risk‐sharing arrangements for households should exploit outside network insurance mechanisms to mitigate welfare losses from terror‐related shocks.
‘I've probably risk assessed this myself’: Choice, control and participant co‐regulation in a disability individualised funding scheme
Authors: Yates Sophie , Dickinson Helen , West Raelene
Published: June 2023

Co‐production is an intrinsic component of disability individualised funding schemes such as Australia's National Disability Insurance Scheme (NDIS). In this paper, we argue that an under‐explored facet of co‐production is the role that users of these services play in co‐regulation. We draw on data collected in a qualitative study exploring participants' use of providers who are not registered with the NDIS regulator, the Quality and Safeguards Commission. Employing Steiner et al.'s (2023) 5Ws framework, we focus particularly on the dimensions of what, why and where to understand the conditions underpinning client co‐regulation of quality and safety in the NDIS. We also explore the various types of activities participants engage in to co‐produce their NDIS services, highlighting activities designed to improve the quality and safety of services delivered by unregistered providers.
Standing Pelvic Tilt Is Associated With Dynamic Pelvic Tilt During Running When Measured by 3-Dimensional Motion Capture
Authors: Mach Madison S. , Ebersole Kyle T. , Ericksen Hayley E. , Nguyen Anh-Dung , Earl-Boehm Jennifer E.
Published: June 2023

Standing pelvic tilt (PT) is related to biomechanics linked with increased risk of injury such as dynamic knee valgus. However, there is limited evidence on how standing PT relates to dynamic PT and whether the palpation meter (PALM), a tool to measure standing PT, is valid against 3-dimensional (3D) motion analysis. The purposes of this study were to (1) determine the criterion validity of the PALM for measuring standing PT and (2) identify the relationship between standing PT and dynamic PT during running. Participants (n = 25; 10 males and 15 females) had their standing PT measured by the PALM and 3D motion analysis. Dynamic PT variables were defined at initial contact and toe off. No relationship between the 2 tools was found. Significant large positive relationships between standing PT and PT at initial contact (r = .751, N = 25, P < .001) and PT at toe off (r = .761, N = 25, P < .001) were found. Since no relationship was found between standing PT measured by the PALM and 3D motion analysis, the PALM is not a valid alternative to 3D motion analysis. Clinicians may be able to measure standing PT and gain valuable information on dynamic PT, allowing clinicians to quickly assess whether further biomechanical testing is needed.
Stabilizing Co
2
C with H
2
O and K promoter for CO
2
hydrogenation to C
2+
hydrocarbons
Authors: Wang Mingrui , Wang Peng , Zhang Guanghui , Cheng Zening , Zhang Mengmeng , Liu Yulong , Li Rongtan , Zhu Jie , Wang Jianyang , Bian Kai , Liu Yi , Ding Fanshu , Senftle Thomas P. , Nie Xiaowa , Fu Qiang , Song Chunshan , Guo Xinwen
Published: June 2023

The decomposition of cobalt carbide (Co
2
C) to metallic cobalt in CO
2
hydrogenation results in a notable drop in the selectivity of valued C
2+
products, and the stabilization of Co
2
C remains a grand challenge. Here, we report an in situ synthesized K-Co
2
C catalyst, and the selectivity of C
2+
hydrocarbons in CO
2
hydrogenation achieves 67.3% at 300°C, 3.0 MPa. Experimental and theoretical results elucidate that CoO transforms to Co
2
C in the reaction, while the stabilization of Co
2
C is dependent on the reaction atmosphere and the K promoter. During the carburization, the K promoter and H
2
O jointly assist in the formation of surface C
*
species via the carboxylate intermediate, while the adsorption of C
*
on CoO is enhanced by the K promoter. The lifetime of the K-Co
2
C is further prolonged from 35 hours to over 200 hours by co-feeding H
2
O. This work provides a fundamental understanding toward the role of H
2
O in Co
2
C chemistry, as well as the potential of extending its application in other reactions.
Relict duck-billed dinosaurs survived into the last age of the dinosaurs in subantarctic Chile
Authors: Alarcón-Muñoz Jhonatan , Vargas Alexander O. , Püschel Hans P. , Soto-Acuña Sergio , Manríquez Leslie , Leppe Marcelo , Kaluza Jonatan , Milla Verónica , Gutstein Carolina S. , Palma-Liberona José , Stinnesbeck Wolfgang , Frey Eberhard , Pino Juan Pablo , Bajor Dániel , Núñez Elaine , Ortiz Héctor , Rubilar-Rogers David , Cruzado-Caballero Penélope
Published: June 2023

In the dusk of the Mesozoic, advanced duck-billed dinosaurs (Hadrosauridae) were so successful that they likely outcompeted other herbivores, contributing to declines in dinosaur diversity. From Laurasia, hadrosaurids dispersed widely, colonizing Africa, South America, and, allegedly, Antarctica. Here, we present the first species of a duck-billed dinosaur from a subantarctic region,
Gonkoken nanoi
, of early Maastrichtian age in Magallanes, Chile. Unlike duckbills further north in Patagonia,
Gonkoken
descends from North American forms diverging shortly before the origin of Hadrosauridae. However, at the time, non-hadrosaurids in North America had become replaced by hadrosaurids. We propose that the ancestors of
Gonkoken
arrived earlier in South America and reached further south, into regions where hadrosaurids never arrived: All alleged subantarctic and Antarctic remains of hadrosaurids could belong to non-hadrosaurid duckbills like
Gonkoken
. Dinosaur faunas of the world underwent qualitatively different changes before the Cretaceous-Paleogene asteroid impact, which should be considered when discussing their possible vulnerability.
Prevalence and predictive modeling of undiagnosed diabetes and impaired fasting glucose in Taiwan: a Taiwan Biobank study
Authors: Chung Ren-Hua , Chuang Shao-Yuan , Chen Ying-Erh , Li Guo-Hung , Hsieh Chang-Hsun , Chiou Hung-Yi , Hsiung Chao A
Published: June 2023

Introduction

We investigated the prevalence of undiagnosed diabetes and impaired fasting glucose (IFG) in individuals without known diabetes in Taiwan and developed a risk prediction model for identifying undiagnosed diabetes and IFG.

Research design and methods

Using data from a large population-based Taiwan Biobank study linked with the National Health Insurance Research Database, we estimated the standardized prevalence of undiagnosed diabetes and IFG between 2012 and 2020. We used the forward continuation ratio model with the Lasso penalty, modeling undiagnosed diabetes, IFG, and healthy reference group (individuals without diabetes or IFG) as three ordinal outcomes, to identify the risk factors and construct the prediction model. Two models were created: Model 1 predicts undiagnosed diabetes, IFG_110 (ie, fasting glucose between 110 mg/dL and 125 mg/dL), and the healthy reference group, while Model 2 predicts undiagnosed diabetes, IFG_100 (ie, fasting glucose between 100 mg/dL and 125 mg/dL), and the healthy reference group.

Results

The standardized prevalence of undiagnosed diabetes for 2012–2014, 2015–2016, 2017–2018, and 2019–2020 was 1.11%, 0.99%, 1.16%, and 0.99%, respectively. For these periods, the standardized prevalence of IFG_110 and IFG_100 was 4.49%, 3.73%, 4.30%, and 4.66% and 21.0%, 18.26%, 20.16%, and 21.08%, respectively. Significant risk prediction factors were age, body mass index, waist to hip ratio, education level, personal monthly income, betel nut chewing, self-reported hypertension, and family history of diabetes. The area under the curve (AUC) for predicting undiagnosed diabetes in Models 1 and 2 was 80.39% and 77.87%, respectively. The AUC for predicting undiagnosed diabetes or IFG in Models 1 and 2 was 78.25% and 74.39%, respectively.

Conclusions

Our results showed the changes in the prevalence of undiagnosed diabetes and IFG. The identified risk factors and the prediction models could be helpful in identifying individuals with undiagnosed diabetes or individuals with a high risk of developing diabetes in Taiwan.
Improving the efficiency of virtual insulin teaching for patients admitted to hospital through the COVID-19 pandemic: a quality improvement initiative
Authors: Tong Jeffery , Meehan Rebecca , Iannicello Dane , Li Raymond , Joy Tisha , Spaic Tamara , Tung Tsan-Hua , Clemens Kristin K
Published: June 2023

Background

Throughout the COVID-19 pandemic, many areas of medicine transitioned to virtual care. For patients with diabetes admitted to hospital, this included diabetes education and insulin teaching. Shifting to a virtual model of insulin teaching created new challenges for inpatient certified diabetes educators (CDE).

Objective

We advanced a quality improvement project to improve the efficiency of safe and effective virtual insulin teaching throughout the COVID-19 pandemic. Our primary aim was to reduce the mean time between CDE referral to successful inpatient insulin teach by 0.5 days.

Design, setting, participants

We conducted this initiative at two large academic hospitals between April 2020 and September 2021. We included all admitted patients with diabetes who were referred to our CDE for inpatient insulin teaching and education.

Intervention

Alongside a multidisciplinary team of project stakeholders, we created and studied a CDE-led, virtual (video conference or telephone) insulin teaching programme. As tests of change, we added a streamlined method to deliver insulin pens to the ward for patient teaching, created a new electronic order set and included patient-care facilitators in the scheduling process.

Main outcome and measures

Our main outcome measure was the mean time between CDE referral and successful insulin teach-back. Our process measure was the percentage of successful insulin pen deliveries to the ward for teaching. As balance measures, we captured the percentage of patients with a successful insulin teach, the time between insulin teach and hospital discharge, and readmissions to hospital for diabetes-related complications.

Results

Our tests of change improved the efficiency of safe and effective virtual insulin teaching by 0.27 days. The virtual model appeared less efficient than usual in-person care.

Conclusions

In our centre, virtual insulin teaching supported patients admitted to hospital through the pandemic. Improving the administrative efficiency of virtual models and leveraging key stakeholders remain important for long-term sustainability.
Unravelling the USP6 gene: an update
Authors: Cordier Fleur , Creytens David
Published: June 2023

Ubiquitin-specific protease 6(USP6) rearrangements have been identified in aneurysmal bone cyst, nodular fasciitis, myositis ossificans, fibro-osseous pseudotumour of digits and cellular fibroma of tendon sheath. These entities show clinical as well as histological overlap, suggesting they are all clonal neoplastic belonging to the same biological spectrum and referred to as ‘USP6-associated neoplasms’. They all show a characteristic gene fusion formed by juxtaposition of theUSP6coding sequences to the promoter regions of several partner genes, leading toUSP6transcriptional upregulation.
First-line treatment of unresectable or metastatic HER2 positive esophagogastric adenocarcinoma: liquid biomarker analysis of the phase 2 INTEGA trial
Authors: Paschold Lisa , Stein Alexander , Thiele Benjamin , Tintelnot Joseph , Henkes Svenja-Sibylla , Coith Cornelia , Schultheiß Christoph , Pantel Klaus , Riethdorf Sabine , Binder Mascha
Published: June 2023

Background

The addition of nivolumab to trastuzumab and chemotherapy in first-line unresectable or metastatic HER2 positive esophagogastric adenocarcinoma (HER2+ EGA) results in long progression-free and overall survival as shown by the INTEGA (ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in HER2 positive esophagogastric adenocarcinoma) trial. This trial suggested that the chemotherapy backbone is needed in an unselected HER2+ patient population. Yet, it remains an open question if there are specific patient subsets that may benefit from an enhanced immunotherapeutic but chemotherapy-free approach.

Methods

We analyzed blood T cell repertoire metrics determined by next-generation sequencing, circulating tumor cell (CTC) counts detected by CellSearch and their expression of HER2 and PD-L1 as potential liquid biomarkers predicting outcomes on ipilimumab versus FOLFOX (folinic acid, FOL, fluorouracil, F, oxaliplatin, OX) chemotherapy added to a backbone of trastuzumab and nivolumab in patients with HER2+ EGA in the INTEGA trial population.

Results

Patients with two out of three baseline-determined liquid biomarkers—high T cell repertoire richness, absence of CTCs or HER2-expression on CTCs—made up approximately 44% of HER2+ EGA cases and did not show compromise in efficacy if treated with a chemotherapy-free regimen. Long-term responders showing a progression-free survival of >12 months were enriched in this biomarker triad, especially if treated on the chemotherapy-free arm.

Conclusion

Prospective validation of this liquid biomarker triad is needed to molecularly define HER2+ EGA patient subsets with different needs in the first-line systemic treatment setting.
Designing with AI
Authors: Chilton Lydia
Published: June 2023

How I came to love design and used AI to alleviate the most frustrating parts of the process.
Machines as Collaborators for Art and Rituals
Authors: E Jane , Fang Cathy Mengying , Bourgault Sam
Published: June 2023

We spoke with artist Sougwen Chung about her views on human-machine collaborations; where her machines are evolving multigenerational configurations of collaborators that drive her understanding of both the emerging technologies and the human experiences of co-creating and collective rituals.
Analysis of Dust Reduction Characteristics of Multistage Tandem Dust Removal System
Authors: Zhang Jiajun , Liang Dong , Cao Yuanwen
Published: June 2023

Asphalt hot regeneration pavement maintenance vehicle is a type of in situ heating waste asphalt special vehicle equipment for mix and regeneration of aged asphalt. When waste asphalt mixture is heated and melted, a lot of organic fumes are typically produced, along with dust from the mixing process. Because of the complex composition of the exhaust gases produced by asphalt hot regeneration pavement maintenance vehicles, it can be difficult to purify and remove them using a single method. In order to effectively purify exhaust gas with complicated compositions, a multistage combined treatment dust removal system structure is presented that includes cyclone sections, spray sections, and adsorption sections. With an emphasis on the cyclone section structure with the dust-gas separation function, computational fluid dynamics (CFD) is used to analyze the internal flow field characteristics, turbulence intensity, tangential velocity, and velocity field vector characteristics. The results reveal that the more symmetrical the distribution of tangential velocity field and static pressure field is, the greater the cyclone dust collector’s dust removal efficiency is, the more stable the flow field is, and the lower the turbulence intensity is. Furthermore, the center cyclone’s growing speed is adversely connected with dust removal effectiveness. As a result, an antiventuri cyclone dust collector with a scrambling column was designed. When the inlet air speed is 6 m/s, the dust removal efficiency of the improved device is 97.0%, which is 5.1% higher than that of the original device, and when the inlet air speed is 8 m/s, the dust removal efficiency of the improved device is 97.3%, which is 4.16% higher than that of the original device. With the increase of the inlet air speed, the difference between them keeps decreasing.
Supplementary Figure S4 from HLA Class II Loss and JAK1/2 Deficiency Coevolve in Melanoma Leading to CD4 T-cell and IFNγ Cross-Resistance
Authors: Stupia Simone , Heeke Christina , Brüggemann Alicia , Zaremba Anne , Thier Beatrice , Kretz Julia , Sucker Antje , Philip Manuel , Zelinskyy Gennadiy , Ferrone Soldano , Roesch Alexander , Horn Susanne , Hadaschik Eva , Schadendorf Dirk , Trilling Mirko , Dittmer Ulf , Griewank Klaus , Zhao Fang , Paschen Annette
Published: June 2023

CD4 T-cell sensitivity of constHLA-II melanoma cells
Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders
Authors: Mairinger Marco , Maget Alexander , Wagner-Skacel Jolana , Mörkl Sabrina , Dalkner Nina , Hellinger Teresa , Birner Armin , Fellendorf Frederike T. , Platzer Martina , Kreuzer Kathrin , Queissner Robert , Reininghaus Bernd , Lenger Melanie , Fabisch Karin , Fitz Werner , Kohlhammer-Dohr Alexandra , Krammer Alexandra , Holl Anna Katharina , Painold Annamaria , Häussl Alfred , Stross Tatjana Maria , Schmiedhofer Franziska , Tmava-Berisha Adelina , Pahsini Karoline , Marinschek Sabine , Wenninger Julian , Hamm Carlo , Pilz René , Lehofer Michael , Amouzadeh-Ghadikolai Omid , Horvath Angela , Kainz Gudrun , Gallé Birgit , Dinan Timothy G. , Butler Mary I. , Reininghaus Eva , Bengesser Susanne
Published: June 2023

Introduction: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. Methods: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. Results: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). Conclusion: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.
The Effect of Oral Simethicone in a Bowel Preparation in a Colorectal Cancer Screening Colonoscopy Setting: A Randomized Controlled Trial
Authors: João Mafalda , Areia Miguel , Alves Susana , Elvas Luís , Brito Daniel , Saraiva Sandra , Cadime Ana Teresa
Published: June 2023

Introduction: Current guidelines suggest adding oral simethicone to bowel preparation for colonoscopy. However, its effect on key quality indicators for screening colonoscopy remains unclear. The primary aim was to assess the rate of adequate bowel preparation in split-dose high-volume polyethylene glycol (PEG), with or without simethicone. Methods: This is an endoscopist-blinded, randomized controlled trial, including patients scheduled for colonoscopy after a positive faecal immunochemical test. Patients were randomly assigned to 4 L of PEG split dose (PEG) or 4 L of PEG split dose plus 500 mg oral simethicone (PEG + simethicone). The Boston Bowel Preparation Scale (BBPS) score, the preparation quality regarding bubbles using the Colon Endoscopic Bubble Scale (CEBuS), ADR, CIR, and the intraprocedural use of simethicone were recorded. Results: We included 191 and 197 patients in the PEG + simethicone group and the PEG group, respectively. When comparing the PEG + simethicone group versus the PEG group, no significant differences in adequate bowel preparation rates (97% vs. 93%; p = 0.11) were found. However, the bubble scale score was significantly lower in the PEG + simethicone group (0 [0] versus 2 [5], p < 0.01), as well as intraprocedural use of simethicone (7% vs. 37%; p < 0.01). ADR (62% vs. 61%; p = 0.86) and CIR (98% vs. 96%, p = 0.14) did not differ between both groups. Conclusion: Adding oral simethicone to a split-bowel preparation resulted in a lower incidence of bubbles and a lower intraprocedural use of simethicone but no further improvement on the preparation quality or ADR.
Diffuse Infiltrating Retinoblastoma with Anterior Chamber Involvement: Conservative Management and Identification of RB1 Alterations in Aqueous Humor
Authors: Cassoux Nathalie , Malaise Denis , Lumbroso-Le Rouic Livia , Le Gall Jessica , Golmard Lisa , Cardoen Liesbeth , Fréneaux Paul , Bouchoucha Yassine , Aerts Isabelle , Doz François , Matet Alexandre
Published: June 2023

Introduction: The aim of the study was to describe the successful conservative management of diffuse infiltrating retinoblastoma (DIR). Identification of RB1 pathogenic variant was done after cell-free DNA (cfDNA) analysis in aqueous humor. Case presentation: Herein, we report 2 patients with unilateral, non-familial DIR with anterior and posterior involvement. Both patients underwent liquid biopsy for tumor cfDNA analysis in aqueous humor. Treatment consisted of a combination of systemic and intra-arterial chemotherapy, with consecutive intracameral and intravitreal injections of melphalan. One patient also required iodine-125 brachytherapy. In both cases, tumor cfDNA analysis revealed biallelic somatic alterations of the RB1 gene. These alterations were not found in germline DNA. Both patients retained their eyes and had a useful vision after a follow-up of 2 years. Conclusion: In selected cases, conservative management of DIR is safe and effective. Tumor cfDNA analysis in aqueous humor is an effective technique to disclose RB1 somatic alterations that guide the germline molecular explorations and improve genetic counseling after conservative treatment.
App-Based Lifestyle Coaching (PINK!) Accompanying Breast Cancer Patients and Survivors to Reduce Psychological Distress and Fatigue and Improve Physical Activity: A Feasibility Pilot Study
Authors: Wolff Josefine , Wuelfing Pia , König Alexander , Ehrl Brigitte , Damsch Jana , Smollich Martin , Baumann Freerk Theeagnus , Harbeck Nadia , Wuerstlein Rachel
Published: June 2023

Introduction: This pilot study aimed to investigate the effects of using an app-based certified medical product named PINK! on breast cancer patients and survivors. The objectives were to measure psychological distress, physical activity, and therapy-related fatigue of patients using PINK! to identify trends and develop a study design for a subsequent multicentric proof of efficacy RCT. Materials and Methods: PINK! offers individualized, evidence-based therapy and side-effect management, mindfulness-based stress reduction, nutritional and psychological education, physical activity tracking, and motivational exercises to implement lifestyle changes sustainably in daily routine. A prospective, intraindividual RCT was performed with n = 60 patients in 2021 at Comprehensive Cancer Center Munich. Patients with BC were included independent of the stage of diseases. The intervention group got access to PINK! over 12 weeks. Control group served as a waiting-list comparison to “standard of care.” Results: Primary efficacy variable analysis revealed a relative average decrease of 32.9% in psychological distress, which corresponds to a statistically significant reduction (p < 0.001) within 12 weeks compared to the control group. Linear regressions within usage groups showed a correlation of high app usage and a reduction of psychological distress. Fatigue data presented a statistically significant antifatigue efficacy (p < 0.001) and physical activity increased by 63.9%. Conclusion: App-based supportive care offers a promising, low-threshold, and cost-efficient opportunity to improve psychological well-being, quality of life, fatigue, and physical activity. More research is needed to implement eHealth solutions in clinical cancer care.
Transient Daratumumab-Induced Refractive Shift in Multidrug-Resistant Multiple Myeloma: Case Report and Literature Review
Authors: Troisi Salvatore , Giudice Valentina , Troisi Mario , Morini Denise , Crudele Andrea , Cuffa Bianca , Selleri Carmine , Serio Bianca
Published: June 2023

Daratumumab, an anti-CD38 monoclonal antibody, is worldwide approved for treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM) patients and is available as intravenous or subcutaneous formulations. Intravenous daratumumab is associated with frequent infusion-related reactions, while eye complications, especially refractive shifts, are very rare, with only previously reported cases. Here, we described a rare case of multi-refractory MM who developed transient myopic shift during intravenous daratumumab infusion successfully treated only with cycloplegic collyrium not requiring infusion rate lowering or drug discontinuation. This conservative therapeutic approach allowed termination of induction therapy and autologous hematopoietic stem-cell transplantation resulting in durable complete remission.
Abstract 10201: Impact of Crohn’s Disease on Mortality and Outcomes in Hospitalized Patients Presenting With Non- St-segment Elevation Myocardial Infarction
Authors: Busari Olukayode , Fatuyi Michael , Oh Jeremy , Akuna Emmanuel , Hegde Sudhanva
Published: June 2023

Introduction:
Crohn's disease is a systemic inflammatory disease with high levels of cytokines that can lead to endothelial damage and atherosclerotic disease. We sought to evaluate the association between Crohn’s disease and mortality in patients hospitalized with Non-ST-Segment Elevation Myocardial Infarction (NSTEMI).

Methods:
Patients hospitalized for NSTEMI with and without Crohn’s disease between 2016 and 2018 were identified from the National Inpatient Sample. The primary outcome was all-cause mortality. The secondary outcomes were cardiac arrest, cardiogenic shock, acute respiratory failure, acute kidney injury, length of stay, and patient charge. A multivariable logistic regression analysis was used to adjust for in-hospital complications. A p-value of <0.05 was considered significant.

Results:
A total of 1,398,309 hospitalized patients with NSTEMI were identified. Of those, 3,356 patients (0.24%) were found to have Crohn's disease. Overall, the mean age was similar (66.4 years vs 68.1 years) among Crohn’s vs non-Crohn's patients. Crohn’s patients had less male (54.4% vs 59.8%) and more Caucasians (84.4% vs 72.5%). The primary outcome did not di!er significantly between the two groups; the rate of mortality was 2.2% in Crohn’s patients and 3.4% patients without Crohn’s disease in hospitalized patients with NSTEMI (Adjusted odds ratio, 0.67; 95% confidence interval, 0.34 to 1.30; p = 0.236). There was no statistical difference between the two groups regarding cardiac arrest, cardiogenic shock, acute respiratory failure, acute kidney injury, length of stay, and patient charge.

Conclusions:
Patients with Crohn’s disease in the setting of NSTEMI did not have a di!erence in mortality or other clinical outcomes when compared with patients without Crohn’s disease. As with most observational studies, causality may not be confirmed due to potential residual confounding.
Abstract 103: Regulation Of Cardiac PTEN/Akt Signaling By Moderate Intra-Ischemic Therapeutic Hypothermia
Authors: Justice Cody N , Zhu Xiangdong , Li Jing , Odonnell J M , Vanden Hoek Terry L
Published: June 2023

Introduction:
Previous studies demonstrate a critical role for Akt in mediating cardioprotection by therapeutic hypothermia. However, the mechanism of hypothermia-induced Akt activation remains poorly understood. Akt activation is determined in part by PTEN activity and degradation.

Hypothesis:
We hypothesized that moderate intra-ischemic cooling activates Akt in the ischemic-reperfused heart due to enhanced PTEN degradation.

Methods:
Rat hearts were isolated and perfused media containing 5 mM glucose. LV function was monitored continuously by an intraventricular balloon. Rate-pressure product (RPP=heart rate x LV developed pressure) was monitored as an index of cardiac function. Hearts in the normothermic control group (I/R) were subjected to 20 min. of global, no-flow ischemia followed by reperfusion at 37 °C. In the hypothermia intervention group (I/R+TH), hearts were cooled to 30 °C at the start of ischemia and then rewarmed 10 min. after reperfusion. Coronary perfusate was collected from the pulmonary artery at preischemic baseline and 10 min. after reperfusion. Ventricular tissue was harvested at 0 or 30 min. after reperfusion for western blotting.

Results:
RPP was significantly higher in the I/R+TH group (n=7) compared to the I/R group (n=8) at 30 min. post-reperfusion (24,725 ± 1,112 mmHg*beats/min. vs. 18,237 ± 2,223 mmHg*beats/min., p<0.05). Coronary perfusate taurine concentration was significantly higher in the I/R group compared to the I/R+TH group at 10 min. post-reperfusion (19 ± 4 μM vs. 5 ± 1 μM, p<0.01). Akt serine473 phosphorylation was significantly
higher
in the I/R+TH group compared to the I/R group at 0 min. post-reperfusion (p<0.01), but significantly
lower
at 30 min. post-reperfusion (p<0.01). Additionally, TH enhanced total PTEN expression at 0 min. (p<0.05) and 30 min. (p<0.01) post-reperfusion without affecting the ratio of phospho-PTEN/PTEN.

Conclusion:
Intra-ischemic cooling was associated with temporal changes in Akt phosphorylation despite enhanced PTEN expression. Additionally, modulation of cardiac taurine release by hypothermia should be carefully considered in future studies assessing taurine as a biomarker for cardiac arrest and ischemic heart pathologies.
Abstract 10714: Disparities in Cardiovascular Investigator-Initiated Research Studies
Authors: Knight Stacey , Le Viet T , Horne Benjamin D , Rasmusson Kismet D , Anderson Jeffrey L , Knowlton Kirk U , May Heidi T , Muhlestein Joseph B
Published: June 2023

Introduction:
Recently there has been a much-needed focus on disparity and inequity in cardiovascular disease (CVD) care. Race, ethnicity, sex, and geography are shown to impact CVD care and outcomes. Perhaps one of the reasons for this is the lack of diversity and representation in CVD research studies, especially in non-sponsored research studies. Here we examine three investigator-initiated clinical CVD trials to describe current enrollment patterns and compare them to the comparable populations.

Methods:
Three Intermountain Healthcare, internally funded, CVD clinical trials were examined. These studies include a pragmatic trial, a randomized unblinded treatment trial, and a biobanking registry. Basic study characteristics and the comparison populations are shown in Table 1.

Results:
Demographic comparisons are shown in Table 2. Females were equally or slightly more represented in the studies. Minority races were under-represented in the pragmatic trial and the biobank registry. Rural or frontier counties were under-represented in the pragmatic trial and randomized trial. Hispanic/Latino patients were under-represented in all studies.

Conclusions
Females were well represented in all studies, but other minority groups were under-represented. The largest under-representation was for Hispanic/Latino patients. The reasons and mechanisms that may lead to under-representation and the impact on research results are unknown and deserve further study. While addressing these disparities may increase research costs (e.g., translation costs), future studies will benefit from the development of new resources and processes, and ultimately could lead to better care.
Abstract 10770: Effects of Glucagon-Like Peptide-1 Receptor Agonists on Patients With or Without Heart Failure: A Meta-Analysis of Randomized Control Trials
Authors: OBATA SHOTA , Miyamoto Yoshihisa , Slipczuk Leandro , Takagi Hisato , Kuno Toshiki
Published: June 2023

Background:
Glucagon-like peptide-1 receptor agonists (GLP -1RAs) reduce the risk of a major adverse cardiovascular event (MACE) and heart failure (HF) in patients with type 2 diabetes mellitus (T2DM). However, these outcomes are not similarly demonstrated in those with HF in subgroup analyses of several randomized controlled trials (RCTs). We evaluated the effect of GLP-1RAs on MACE and HF admissions for T2DM patients with the previous history of HF.

Methods:
We searched PubMed and EMBASE through March 2022 to identify RCTs examining the effects of GLP-1RAs compared to placebo on MACE and HF admission in T2DM patients with a history of HF. MACE was mainly defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke. We performed a meta-analysis with random effects model.

Results:
Our analysis included subgroup analyses of 7 RCTs enrolling a total of 8,965 patients with T2DM and history of HF. Pooled analysis demonstrated a significant decreased MACE (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.78-0.99; P = 0.039; I2 = 18.1%) in the GLP-1RAs group (Figure 1A). In contrast, the rate of HF admission was not significantly different between the both groups (HR, 1.03; 95% CI, 0.91-1.16; P = 0.67; I2 = 0.0%) (Figure 1B).

Conclusions:
GLP-1RAs significantly reduced MACE in patients with HF and T2DM compared to the placebo group but did not affect the risk of HF admission in both groups.
Abstract 10909: A Novel ATP Citrate Lyase-Dependent Metabolic-Transcriptional Axis in Pulmonary Arterial Hypertension
Authors: Bonnet Sebastien , Romanet Charlotte , Grobs Yann , Lemay Sarah-Eve , Bourgeois Alice , Breuils-bonnet Sandra , Martineau Sandra , SALEM MABROUKA , Potus Francois , Provencher Steeve , Boucherat Olivier
Published: June 2023

INTRODUCTION:
Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary artery smooth muscle (PASMC) proliferation and suppressed apoptosis. In cancer, the sustainability of this phenotype required metabolic adaptation (Warburg effect / lipid synthesis) influencing chromatin structure and gene expression. By producing Acetyl coA the ATP Citrate Lyase (ACLY) has emerged as a key player in cancer by favoring Warburg effect, lipid synthesis and histone acetylation.

We hypothesized that ACLY is upregulated in PAH and supports PAH-PASMC proliferation and contributes to PA remodelling.

METHODS/RESULTS:
The implication of ACLY in PAH was demonstrated by
1)
an upregulation (n=10 p<0.05) of its expression, activation (P-ACLY) and nuclear localization in human PAH lungs, PASMCs and experimental PAH models (sugen/hypoxia, Su/Hx rats and mice) compared to control (immunoblot/immunofluorescence);
2)
mice with ACLY deleted in SMCs did not develop Su/Hx-induced PA remodelling and PAH (n=20 p<0.05). Mechanistically, ACLY inhibition (siRNA/BMS) decreased proliferation (Ki67/PCNA) and increased apoptosis (AnnexinV / Survivin) in PAH-PASMCs (n=8 p<0.05). These effects were associated with the inhibition of multiple genes linked to cell cycle, metabolism and lipid synthesis (RNAseq p<0.05 n=6) leading to a decrease (p<0.05) in Warburg effect (LDH, PKM2, P-PDH) and an increase in OCR/ECAR (seahorse). These findings were coupled with an inhibition of the histone acetyl-transferase P300 and histones H3/H4 acetylation. Motif enrichment analyses of transcriptomic datasets identified NFY, NFAT and FOXM1 (all involved in PAH and P300 regulated) as putative transcription factors implicated in ACLY-dependent gene regulation in PAH. This will be confirmed by CHIPseq/ATACseq. In vivo, effects of ACLY inhibitors (BMS/ETC1002) were assessed in rats with Su/Hx-PAH. Both decreased PA pressure, resistance, wall thickness and improved right ventricular functions (n=20; p<0.05) (Echo/catheterization).

CONCLUSION:
We uncovered a novel ACLY-dependent metabolic-transcriptional axis explaining how PASMCs proliferate and survive in PAH. ACLY inhibition is an attractive therapeutic strategy to improve PAH as ETC1002 is clinically advanced.