bluuebunny/crossref_metadata_2025 huggingface dataset:
A look at the GLP‐1 agonists
Authors: Price Lawrence H.
Published: July 2023

A couple of years ago, I started exercising at home instead of going to the local Y. I'd typically have a television cable news channel on to keep me company, and was thereby subjected to abundant commercial advertising. Aside from marveling at the remarkably precise targeting of my demographic (old people), I pretty much managed to tune out the content. Recently, however, during more purposeful encounters with the media, I have found myself inundated with discussions of a specific product I had previously only associated with a strikingly annoying jingle: Ozempic.
Achieving High Fill Factor in Efficient P‐i‐N Perovskite Solar Cells
Authors: Shi Junwei , Zhao Chenyu , Yuan Jianyu
Published: July 2023

Lead halide perovskite solar cells (PSCs) have made unprecedented progress, exhibiting great potential for commercialization. Among them, inverted p‐i‐n PSCs provide outstanding compatibility with flexible substrates, more importantly, with silicon (Si) bottom devices for higher efficiency perovskite‐Si tandem solar cells. However, even with recently obtained efficiency over 25%, the investigation of inverted p‐i‐n PSCs is still behind the n‐i‐p counterpart so far. Recent progress has demonstrated that the fill factor (FF) in inverted PSCs currently still underperforms relative to open‐circuit voltage and short‐circuit current density, which requires an in‐depth understanding of the mechanism and further research. In this review article, the recent advancements in high FF inverted PSCs by adopting the approaches of interfacial optimization, precursor engineering as well as fabrication techniques to minimize undesirable recombination are summarized. Insufficient carrier extraction and transport efficiency are found to be the main factors that hinder the current FF of inverted PSCs. In addition, insights into the main factors limiting FF and strategies for minimizing series resistance in inverted PSCs are presented. The continuous efforts dedicated to the FF of high‐performance inverted devices may pave the way toward commercial applications of PSCs in the near future.
Bacteriosynthetic Degradable Tranexamic Acid‐Functionalized Short Fibers for Inhibiting Invisible Hemorrhage
Authors: Bao Luhan , Zhang Zhiqiang , Li Xiaoxiao , Zhang Lei , Tian Hua , Zhao Minwei , Ye Tingjun , Cui Wenguo
Published: July 2023

Current research on hemostatic materials have focused on the inhibition of visible hemorrhage, however, invisible hemorrhage is the unavoidable internal bleeding that occurs after trauma or surgery, leading directly to a dramatic drop in hemoglobin and then to anemia and even death. In this study, bacterial nanocellulose (BNC) was synthesized and oxidized from the primary alcohols to carboxyl groups, and then grafted with tranexamic acid through amide bonds to construct degradable nanoscale short fibers (OBNC‐TXA), which rapidly activated the coagulation response. The hemostatic material is made up of nanoscale short fibers that can be constructed into different forms such as emulsions, gels, powders, and sponges to meet different clinical applications. In the hemostatic experiments in vitro, the composites had significantly superior pro‐coagulant properties due to the rapid aggregation of blood cells. In the coagulation experiments with rat tail amputation and liver trauma hemorrhage models, the group treated with OBNC‐TXA1 sponge showed low hemorrhage and inhibited invisible hemorrhage in rectus abdominis muscle defect hemorrhage models, with a rapid recovery of hemoglobin values from 128±5.5 to 165±2.6 g L−1 within 4 days. In conclusion, the degradable short fibers constructed from bacterial nano‐cellulose achieved inhibition of invisible hemorrhage in vivo.
Revealing the Role of Active Fillers in Li‐ion Conduction of Composite Solid Electrolytes
Authors: Xue Shida , Chen Shiming , Fu Yanda , Zhu Hengyao , Ji Yuchen , Song Yongli , Pan Feng , Yang Luyi
Published: July 2023

Composite solid electrolytes (CSEs) consisting of polyethylene oxide (PEO) matrix and active inorganic fillers have shown great potential for practical applications. However, mechanisms of how different active fillers enhance ion transport in CSEs still remain inconclusive. In this work, the component dependencies of ionic conductivity of PEO‐based CSEs are investigated by comparing two widely investigated active fillers: NASICON‐type (LATP) and garnet‐type (LLZTO). In terms of ionic conductivity, the optimum ratios are strikingly different for LLZTO (10 wt%) and LATP (50 wt%). Through experimental and computational studies, it is demonstrated that the high affinity between LATP and PEO facilitates unhindered interfacial Li+ transfer so that LATP functions as a bulk‐active filler to provide additional inorganic ion pathways. By contrast, Li+ transfer between LLZTO and PEO is found to be sluggish. Instead, LLZTO mainly improves ionic conductivity by dissociating lithium salt, making it a surface‐active filler. Through categorizing active fillers based on their Li+ conductive mechanisms, this work provides new understanding and guidelines for componential design and optimization of solid composite electrolytes.
Serum C‐reactive protein concentrations in dogs with structural and idiopathic epilepsy
Authors: Mahon Elizabeth K. , Williams Tim L. , Alves Lisa
Published: July 2023

Background

C‐reactive protein (CRP) is an acute‐phase protein produced by the liver during systemic inflammation. In humans, some epilepsies are associated with increased serum CRP (sCRP) concentrations, but this has yet to be proven in veterinary studies. Dogs with structural epilepsy (SE) and normal interictal neurological examination are hard to distinguish from dogs with idiopathic epilepsy (IE) without the use of advanced imaging.

Methods

The study included eight dogs with SE and 12 dogs with IE from a referral hospital population. This was a retrospective observational cohort study. The Mann–Whitney test was used to compare the sCRP concentrations within 24 hours of the last epileptic seizure between dogs with SE or IE.

Results

Dogs with SE had higher sCRP concentrations than dogs with IE (8.9 [range <2.2–53.2] mg/L vs. <2.2 [range <2.2–6.9] mg/L; p = 0.043). Five of the eight (62%) dogs with SE had an sCRP concentration above the reference interval, compared with none of the 12 dogs with IE.

Limitations

The small sample size was the major limitation of this study. Other inflammatory causes were also not exclusively ruled out, although further clinical investigations were not indicated.

Conclusions

This study found that sCRP concentrations were higher in this cohort of dogs with SE than in those with IE. Further studies with larger cohorts of dogs are warranted to validate if sCRP can be used as an additional biomarker for SE.
Value of [68Ga]Ga‐FAPI‐04 PET imaging in acute coronary syndrome complicated by suspected gastrointestinal malignancies
Authors: Ying Mingzhen , Yang Qinqin , Xu Xudong , Wu Shengyong , Yin Wei , Liang Siyu , Pan Guixia , Zuo Changjing , Guo Zhifu , Cheng Chao , Liu Suxuan
Published: July 2023

Early diagnosis of gastrointestinal malignancies in patients with acute coronary syndrome (ACS) is often delayed. The present study aims to demonstrate the value of [68Ga]Ga‐FAPI‐04 PET imaging in ACS with suspected gastrointestinal malignancies. Twelve ACS patients with suspected gastrointestinal malignancies were enrolled, including ST‐elevation myocardial infarction (STEMI) (n = 5), non‐ST‐elevation myocardial infarction (NSTEMI) (n = 5), and unstable angina (UA) (n = 2). All patients underwent coronary angiography (CAG) and [68Ga]Ga‐FAPI‐04 PET/MR or PET/CT within 1 week. All five STEMI and five NSTEMI patients had high [68Ga]Ga‐FAPI‐04 uptake in the injured myocardium compared to remote area (TBR: 2.10 ± 0.72 vs. 0.62 ± 013; p < .001), correlated with peak cTnI level (R = .82, p = .004). No [68Ga]Ga‐FAPI‐04 in the myocardium was found in UA patients. NSTEMI displayed a similar myocardial [68Ga]Ga‐FAPI‐04 intensity as STEMI (p = .42). Compared with STEMI, NSTEMI patients had a significantly delayed door‐to‐balloon time for reperfusion treatment (p = .023). High uptake of [68Ga]Ga‐FAPI‐04 in the gastrointestinal tract was detected in three patients. Because of no myocardial [68Ga]Ga‐FAPI‐04 expression, they discontinued antiplatelet therapy and underwent endoscopy. The rectal, colon, and gastric cancer diagnoses were made by biopsy. The other nine patients showed no accumulation of [68Ga]Ga‐FAPI‐04 beyond the heart, and invasive tumor examinations were delayed. During a median 6‐month follow‐up, no tumor formation was observed. [68Ga]Ga‐FAPI‐04 PET imaging is valuable to assess injured myocardium, detect tumors, and guide invasive examinations in ACS patients with suspected gastrointestinal malignancies.
Two-loop corrections to Lamb shift and hyperfine splitting in hydrogen via multi-loop methods
Authors: Krachkov Petr A. , Lee Roman N.
Published: July 2023

Abstract

We revisit the contributions of order α2(Zα)5m and α2(Zα)EF, respectively, to the Lamb shift and to the hyperfine splitting from mixed self-energy-vacuum-polarization diagrams, involving fermionic loop. We use modern multi-loop calculation techniques based on IBP reduction and differential equations. We construct the ϵ-regular basis [1] and explicitly demonstrate that it is compatible with the renormalization. We obtain analytic results in terms of one-fold integral involving elliptic function and dilogarithm. As a by-product, we obtain the analogous contribution for the limiting cases of heavy and light fermionic loop.
Collagen VI sustains cell stemness and chemotherapy resistance in glioblastoma
Authors: Cescon Matilde , Rampazzo Elena , Bresolin Silvia , Da Ros Francesco , Manfreda Lorenzo , Cani Alice , Della Puppa Alessandro , Braghetta Paola , Bonaldo Paolo , Persano Luca
Published: July 2023

Microenvironmental factors are known fundamental regulators of the phenotype and aggressiveness of glioblastoma (GBM), the most lethal brain tumor, characterized by fast progression and marked resistance to treatments. In this context, the extracellular matrix (ECM) is known to heavily influence the behavior of cancer cells from several origins, contributing to stem cell niches, influencing tumor invasiveness and response to chemotherapy, mediating survival signaling cascades, and modulating inflammatory cell recruitment. Here, we show that collagen VI (COL6), an ECM protein widely expressed in both normal and pathological tissues, has a distinctive distribution within the GBM mass, strongly correlated with the most aggressive and phenotypically immature cells. Our data demonstrate that COL6 sustains the stem-like properties of GBM cells and supports the maintenance of an aggressive transcriptional program promoting cancer cell proliferation and survival. In particular, we identified a specific subset of COL6-transcriptionally co-regulated genes, required for the response of cells to replicative stress and DNA damage, supporting the concept that COL6 is an essential stimulus for the activation of GBM cell response and resistance to chemotherapy, through the ATM/ATR axis. Altogether, these findings indicate that COL6 plays a pivotal role in GBM tumor biology, exerting a pleiotropic action across different GBM hallmarks, including phenotypic identity and gene transcription, as well as response to treatments, thus providing valuable information for the understanding of the complex microenvironmental cues underlying GBM malignancy.
SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study
Authors: Anson Matthew , Zhao Sizheng S. , Austin Philip , Ibarburu Gema H. , Malik Rayaz A. , Alam Uazman
Published: July 2023

Aims/hypothesis

Insulin is the primary treatment for type 1 diabetes. However, alternative glucose-lowering therapies are used adjunctively, but importantly are off-label in type 1 diabetes. Little work has previously been undertaken to evaluate safety with long-term efficacy and cardio-renal benefits of such therapies. We sought to investigate the real-world impact of sodium–glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with type 1 diabetes in relation to effect on blood glucose levels, adverse events and cardio-renal outcomes.

Methods

We performed a retrospective cohort study of all patients aged 18 or over with type 1 diabetes on the TriNetX platform, a global collaborative network providing access to real-time, anonymised medical records. We included patients who had been treated with an SGLT2i or GLP-1 RA for at least 6 months and analysed the efficacy, safety and cardio-renal outcomes 5 years after initiation of therapy.

Results

We identified 196,691 individuals with type 1 diabetes, 13% of whom were treated with adjunctive glucose-lowering therapy in addition to insulin. Included in the core analysis were 1822 patients treated with a GLP-1 RA and 992 individuals treated with an SGLT2i. Both agents provided clinically meaningful reductions in HbA1c (−2.6 mmol/mol [−0.2%] with SGLT2i and −5.4 mmol/mol [−0.5%] with GLP-1 RA). The SGLT2i treated cohort showed preservation of eGFR over a 5-year period compared with the GLP-1 RA treated cohort (+3.5 ml/min per 1.73 m2 vs −7.2 ml/min per 1.73 m2, respectively), including patients with established chronic kidney disease (CKD). The SGLT2i treated cohort experienced higher rates of diabetic ketoacidosis (DKA) (RR 2.08 [95% CI 1.05, 4.12] p=0.0309) and urinary tract infection/pyelonephritis (RR 2.27 [95% CI 1.12, 4.55] p=0.019) compared with the GLP-1 RA treated cohort. However, the SGLT2i treated cohort were less likely to develop heart failure (RR 0.44 [95% CI 0.23, 0.83] p=0.0092), CKD (RR 0.49 [95% CI 0.28, 0.86] p=0.0118) and be hospitalised for any cause (RR 0.59 [95% CI 0.46, 0.76] p≤0.0001) when compared with the GLP-1 RA treated cohort.

Conclusions/interpretation

Both SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes.

Graphical Abstract
Notwendigkeit von SOPs am Beispiel der postpartalen Hämorrhagie
Authors: Brun Romana
Published: July 2023

Die postpartale Blutung stellt eine Notfallsituation in der Geburtshilfe dar und ist immer noch eine der häufigsten Ursachen für mütterliche Morbidität und Mortalität weltweit. Verschiedene Analysen der schwangerschaftsassoziierten Todesfälle konnten im Nachhinein darstellen, dass ein Drittel bis ein Viertel vermeidbar gewesen wäre, z. B.: durch Verbesserung der sog. nichttechnischen Fertigkeiten. Unter dem Begriff „standard operating procedure“ (SOP oder auch standardisierte Vorgehensweisen) versteht man ein allgemeingültiges, standardisiertes Vorgehen von Abläufen in kritischen Bereichen wie in der Medizin. Viele internationale Fachgesellschaften fordern festgelegte Vorgehensweisen zur Verbesserung der Qualität zur Bewältigung der postpartalen Blutung. Die Implementierung von SOP ist deshalb ein wichtiger Grundpfeiler für den Erfolg der Behandlung der postpartalen Blutung. Es sollte zudem auch eine Plattform geben zu Repetition und Trainings dieser Vorgehensweisen.
Revisiting the conservativity of fixpoints over intuitionistic arithmetic
Authors: Granberg Olsson Mattias , Leigh Graham E.
Published: July 2023

This paper presents a novel proof of the conservativity of the intuitionistic theory of strictly positive fixpoints, $$\widehat{{\textrm{ID}}}{}_{1}^{{\textrm{i}}}{}$$

ID
^

1

i

, over Heyting arithmetic ($${\textrm{HA}}$$
HA
), originally proved in full generality by Arai (Ann Pure Appl Log 162:807–815, 2011. https://doi.org/10.1016/j.apal.2011.03.002). The proof embeds $$\widehat{{\textrm{ID}}}{}_{1}^{{\textrm{i}}}{}$$

ID
^

1

i

into the corresponding theory over Beeson’s logic of partial terms and then uses two consecutive interpretations, a realizability interpretation of this theory into the subtheory generated by almost negative fixpoints, and a direct interpretation into Heyting arithmetic with partial terms using a hierarchy of satisfaction predicates for almost negative formulae. It concludes by applying van den Berg and van Slooten’s result (Indag Math 29:260–275, 2018. https://doi.org/10.1016/j.indag.2017.07.009) that Heyting arithmetic with partial terms plus the schema of self realizability for arithmetic formulae is conservative over $${\textrm{HA}}$$
HA
.
Simulation of machining behaviour of two-phase brittle materials during grinding by modelling single-grain scratching using a combination of FE and SPH methods
Authors: Dehmer Alexander , Prinz Sebastian , Breuer Peter , Barth Sebastian , Bergs Thomas
Published: July 2023

Two-phase, brittle-hard materials are widely used not only in the tool industry but also increasingly in the aerospace industry. Due to the two-phase nature, the materials have unique material properties adapted to the respective application. But the material properties also lead to challenging machinability. Therefore, two-phase, brittle-hard materials are mostly ground. The analogy process of single-grain scratching is used to analyse the material removal behaviour and design the grinding process. Since single-grain scratching is time-consuming and costly, it is desirable to substitute the analogy process with numerical simulation. This paper discusses the suitability of the Smooth Particle Hydrodynamic (SPH) simulation method in combination with the Finite Element Method (FEM) for single-grain scratching of two-phase, brittle-hard materials. The approach is validated using the examples of tungsten carbide-cobalt (WC-Co) cemented carbides and Silicon carbide fibre-reinforced silicon carbide (SiC/SiC) ceramics. For both applications, the material removal behaviour was optically analysed and in good agreement with the experimental results and theoretical assumptions. For SiC/SiC ceramics, several surface phenomena could be identified in the simulation as well as in the experimental results. The scratching forces were compared qualitatively and were in good agreement with the experimental results for both applications.
Development and evaluation of a closed-loop z-axis control strategy for wire-and-arc-additive manufacturing using the process signal
Authors: Hölscher Lennart Vincent , Hassel Thomas , Maier Hans Jürgen
Published: July 2023

Wire-and-arc-additive manufacturing (WAAM) is an additive manufacturing technology with a high deposition rate. WAAM usually employs a layer wise build-up strategy. This makes it necessary to know the height of each deposited layer to determine the height the z-axis has to travel after each layer. Current bead geometry models (BGM) lead to variations, which can gradually accumulate over the layers. The present study focuses on the development of a closed-loop control system capable of keeping the contact tube working distance (CTWD) constant during short-circuit gas metal arc welding (GMAW) based WAAM. The algorithm calculates the CTWD based on the resistance during the short circuit. The closed-loop strategy is compared to an open-loop control strategy, which moves along a predefined height step after each layer. Using the proposed control strategy, WAAM becomes a fully automated process without the need for preliminary experiments to determine the height step. Only a short calibration slope is necessary for a complete closed-loop additive build-up. To study the influence of the control strategy on the workpiece the energy input, mechanical strength, microhardness, porosity, and microstructure were analyzed. It is shown that the CTWD of the open-loop deposited component increases slowly. Due to the novel control approach, this is prevented by the closed-loop control, while the mechanical strength and microhardness remain.
Graphene nanoplatelets reinforced Al-Cu-Mg composite fabricated using laser powder bed fusion: microstructure, mechanical properties, and wear behaviour
Authors: Pekok Mulla Ahmet , Setchi Rossitza , Ryan Michael , Brousseau Emmanuel , Han Quanquan , Gu Dongdong
Published: July 2023

Aluminium-based metal matrix composites reinforced with graphene (Gr) and its derivatives have been reported as promising composites due to their superior properties such as strength, damage tolerance, fatigue resistance, and density. However, the crack and porosity susceptibility of Aluminium 2024 Alloy (AA2024) with added Gr when fabricated using additive manufacturing techniques is not sufficiently well understood. The present work addresses this knowledge gap by focusing on the effect of graphene nanoplatelets (GNPs) and scanning speed on the AA2024 composites’ wear performance and microstructural and mechanical properties of specimens fabricated using laser powder bed fusion (LPBF). The experimental findings demonstrate that up to 0.5% presence of Gr in the composite improves its crystallite size and microhardness by up to 37.6% and 45%, respectively; however, it increases the porosity and crack formation due to the high laser power requirement. Moreover, the composites’ macroscale scratch and nanoscale wear performances showed improvements by up to 50% and 56% with higher Gr concentration (0.5%), suggesting that Gr is distributed uniformly in the structure. The improved understanding of the relationship between microstructure and mechanical characteristics of the GNPs/Al2024 composites fabricated using LPBF in terms of cracking and porosity formation is another significant contribution of this work.

Graphical abstract
Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment
Authors: Maldonado Maria del Mar , Schlom Jeffrey , Hamilton Duane H.
Published: July 2023

The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment.
Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis
Authors: Cheung Wing Keung , Pakzad Ashkan , Mogulkoc Nesrin , Needleman Sarah , Rangelov Bojidar , Gudmundsson Eyjolfur , Zhao An , Abbas Mariam , McLaverty Davina , Asimakopoulos Dimitrios , Chapman Robert , Savas Recep , Janes Sam M. , Hu Yipeng , Alexander Daniel C. , Hurst John R. , Jacob Joseph
Published: July 2023

Objectives

The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF).

Methods

In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT.

Results

No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66–0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22–2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco.

Conclusions

AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value.

Clinical relevance statement

Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree.

Key Points

• AirQuant generates measures of intersegmental tapering and segmental tortuosity.

• Automated airway quantification associates with mortality in IPF independent of established measures of disease severity.

• Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF.

Graphical Abstract
Trust and stakeholder perspectives on the implementation of AI tools in clinical radiology
Authors: Bergquist Magnus , Rolandsson Bertil , Gryska Emilia , Laesser Mats , Hoefling Nickoleta , Heckemann Rolf , Schneiderman Justin F. , Björkman-Burtscher Isabella M.
Published: July 2023

Objectives

To define requirements that condition trust in artificial intelligence (AI) as clinical decision support in radiology from the perspective of various stakeholders and to explore ways to fulfil these requirements.

Methods

Semi-structured interviews were conducted with twenty-five respondents—nineteen directly involved in the development, implementation, or use of AI applications in radiology and six working with AI in other areas of healthcare. We designed the questions to explore three themes: development and use of AI, professional decision-making, and management and organizational procedures connected to AI. The transcribed interviews were analysed in an iterative coding process from open coding to theoretically informed thematic coding.

Results

We identified four aspects of trust that relate to reliability, transparency, quality verification, and inter-organizational compatibility. These aspects fall under the categories of substantial and procedural requirements.

Conclusions

Development of appropriate levels of trust in AI in healthcare is complex and encompasses multiple dimensions of requirements. Various stakeholders will have to be involved in developing AI solutions for healthcare and radiology to fulfil these requirements.

Clinical relevance statement

For AI to achieve advances in radiology, it must be given the opportunity to support, rather than replace, human expertise. Support requires trust. Identification of aspects and conditions for trust allows developing AI implementation strategies that facilitate advancing the field.

Key Points

• Dimensions of procedural and substantial demands that need to be fulfilled to foster appropriate levels of trust in AI in healthcare are conditioned on aspects related to reliability, transparency, quality verification, and inter-organizational compatibility.

•Creating the conditions for trust to emerge requires the involvement of various stakeholders, who will have to compensate the problem’s inherent complexity by finding and promoting well-defined solutions.
Information extraction from weakly structured radiological reports with natural language queries
Authors: Dada Amin , Ufer Tim Leon , Kim Moon , Hasin Max , Spieker Nicola , Forsting Michael , Nensa Felix , Egger Jan , Kleesiek Jens
Published: July 2023

Objectives

Provide physicians and researchers an efficient way to extract information from weakly structured radiology reports with natural language processing (NLP) machine learning models.

Methods

We evaluate seven different German bidirectional encoder representations from transformers (BERT) models on a dataset of 857,783 unlabeled radiology reports and an annotated reading comprehension dataset in the format of SQuAD 2.0 based on 1223 additional reports.

Results

Continued pre-training of a BERT model on the radiology dataset and a medical online encyclopedia resulted in the most accurate model with an F1-score of 83.97% and an exact match score of 71.63% for answerable questions and 96.01% accuracy in detecting unanswerable questions. Fine-tuning a non-medical model without further pre-training led to the lowest-performing model. The final model proved stable against variation in the formulations of questions and in dealing with questions on topics excluded from the training set.

Conclusions

General domain BERT models further pre-trained on radiological data achieve high accuracy in answering questions on radiology reports. We propose to integrate our approach into the workflow of medical practitioners and researchers to extract information from radiology reports.

Clinical relevance statement

By reducing the need for manual searches of radiology reports, radiologists’ resources are freed up, which indirectly benefits patients.

Key Points

• BERT models pre-trained on general domain datasets and radiology reports achieve high accuracy (83.97% F1-score) on question-answering for radiology reports.

• The best performing model achieves an F1-score of 83.97% for answerable questions and 96.01% accuracy for questions without an answer.

• Additional radiology-specific pretraining of all investigated BERT models improves their performance.

Graphical Abstract
Impact of virtual reality training on mastoidectomy performance: a prospective randomised study
Authors: Tapiala Jesse , Iso-Mustajärvi Matti , Timonen Tomi , Vrzáková Hana , Dietz Aarno
Published: July 2023

Purpose

The opportunities for surgical training and practice in the operating room are in decline due to limited resources, increased efficiency demands, growing complexity of the cases, and concerns for patient safety. Virtual reality (VR) offers a novel opportunity to enhance surgical training and provide complementary three-dimensional experience that has been usually available in the operating room. Since VR allows viewing and manipulation of realistic 3D models, the VR environment could enhance anatomical and topographical knowledge, in particular. In this study, we explored whether incorporating VR anatomy training improves novices’ performance during mastoidectomy over traditional methods.

Methods

Thirty medical students were randomized into two groups and taught mastoidectomy in a structured manner. One group utilized a VR temporal bone model during the training while the other group used more traditional materials such as anatomy books. After the training, all participants completed a mastoidectomy on a 3D-printed temporal bone model under expert supervision. Performance during the mastoidectomy was evaluated with multiple metrics and feedback regarding the two training methods was gathered from the participants.

Results

The VR training method was rated better by the participants, and they also needed less guidance during the mastoidectomy. There were no significant differences in operational time, the occurrence of injuries, self-assessment scores, and the surgical outcome between the two groups.

Conclusion

Our results support the utilization of VR training in complete novices as it has higher trainee satisfaction and leads to at least as good results as the more traditional methods.
Inverse pattern of GABAergic system impairment in the external versus internal globus pallidus in male heroin addicts
Authors: Gos Anna , Steiner Johann , Trübner Kurt , Ungewickell Jonas , Mawrin Christian , Karnecki Karol , Kaliszan Michał , Gos Tomasz
Published: July 2023

Opioid addiction is a global problem that has been exacerbated in the USA and Europe by the COVID-19 pandemic. The globus pallidus (GP) plays a prominent neurobiological role in the regulation of behaviour as an output station of the striato-pallidal system. GABAergic large projection neurons are the main neuronal type in the external (EGP) and internal (IGP) parts of the GP, where addiction-specific molecular and functional abnormalities occur. In these neurons, glutamate decarboxylase (GAD) with isoforms GAD 65 and 67 is a key enzyme in GABA synthesis, and experimental studies suggest GAD dysregulation in the GP of heroin addicts. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of large GP neurons by densitometric evaluation of their GAD 65/67-immunostained thick dendrites. The study revealed a bilaterally decreased fibres density in the EGP paralleled by the increase in the IGP in 11 male heroin addicts versus 11 healthy controls (significant U-test P values). The analysis of confounding variables found no interference of age, brain volume, and duration of formalin fixation with the results. Our findings suggest a dysregulation of GABAergic activity in the GP of heroin addicts, which is consistent with experimental data from animal models and plays potentially a role in the disturbed function of basal ganglia circuit in opioid addiction.
Unlocking customer flexibilities through standardized communication interfaces
Authors: Reihs David , Bouda Fabian , Leimgruber Fabian , Machtinger Katharina , Strasser Thomas I. , Stefan Mark , Einfalt Alfred , Schober Lukas
Published: July 2023

The need for a more sustainable energy system is leading to more electric energy generation being connected to low voltage (LV) distribution grids. At the same time, due to accelerated growth in electric mobility and heat pumps, more and more energy consumed by end customers is supplied via LV distribution grids. These developments cause distribution networks to become less predictable and make them subject to much higher changes in supply and demand. Therefore, additional flexibility will be needed to keep such systems operating with high quality of service. The required flexibility could be provided by distributed generators as well as flexible loads. This leads to the question of how these flexibilities can be activated by distribution system operators when needed. A digital interface between distribution system operator and device operator could be implemented to communicate flexibility requirements. In this work, three possible deployment scenarios for such a digital interface are presented. A market review of available standards and commonly implemented communication protocols was conducted to identify potential candidates for the standardization of such an interface.
Using mixed methods and community participation to explore household and ambient air pollution practices in a rural community in Malawi
Authors: Phillip Eunice , Conroy Ronan M. , Walsh Aisling , Jumbe Vincent , Jewitt Sarah , Lee Shona , Stanistreet Debbi
Published: July 2023

Aim

Globally, household and ambient air pollution (HAAP) accounts for almost 7 million premature deaths each year. Over half of these are from incomplete biomass fuel combustion in open fires and inefficient cookstoves. Solutions to the problem remain challenging due to cost, people’s perception of pollution and unsuitability to meet user needs.

Subject and methods

We used mixed methods and participatory approaches to measure and understand practices and beliefs relating to HAAP in a low-resource community in Malawi. Eighty-six households were randomly sampled for the survey, fine particulate matter (PM2.5) levels were measured in 46 kitchens and four ambient locations, and 38 households were engaged during participatory transect walks. We analysed the data using descriptive and thematic analysis.

Results

Kitchen PM2.5 levels far exceeded the World Health Organization’s recommended safe levels. Open-burning practices further contributed to ambient air pollution in the community. While there was high awareness of smoke in cooking areas, participants did not associate it with adverse health outcomes. Availability and affordability of cleaner alternatives influenced household energy choices. Integrating participatory methods alongside quantitative data allowed an in-depth understanding of the community’s practices and relationship with HAAP.

Conclusion

The findings demonstrate that energy poverty is a key factor in access to clean energy sources and highlight the importance of engaging communities to design HAAP interventions that meet their physical, socioeconomic and cultural needs.
Active pairwise distance learning for efficient labeling of large datasets by human experts
Authors: Pries Joris , Bhulai Sandjai , van der Mei Rob
Published: July 2023

In many machine learning applications, the labeling of datasets is done by human experts, which is usually time-consuming in cases of large data sets. This raises the need for methods to make optimal use of the human expert by selecting model instances for which the expert opinion is of most added value. This paper introduces the problem of active pairwise distance learning (APDL), where the goal is to actively learn the pairwise distances between all instances. Any distance function can be used, which means that APDL techniques can e.g., be used to determine likeness between faces or similarities between users for recommender systems. Starting with an unlabeled dataset, each round an expert determines the distance between one pair of instances. Thus, there is an important choice to make each round: ‘Which combination of instances is presented to the expert?’ The objective is to accurately predict all pairwise distances, while minimizing the usage of the expert. In this research, we establish upper and lower bound approximations (including an update rule) for the pairwise distances and evaluate many domain-independent query strategies. The observations from the experiments are therefore general, and the selection strategies are ideal candidates to function as baseline in future research. We show that using the criterion max degree consistently ranks amongst the best strategies. By using this criterion, the pairwise distances of a new dataset can be labeled much more efficiently.
How do HEIs’ students accept nudging? Expert perspective analysis
Authors: Ochrana František , Korečková Jana , Kovács Radek
Published: July 2023

The study examines the influence of nudging on the successful studies of Higher education institutions (HEI’s) students. Data from one of the typical countries of the Central European region (Czech Republic) is analyzed. The goal of the research was to find out how students accept individual forms of nudging. For this purpose, a questionnaire survey at Czech HEIs (N = 207) and structured interviews with experts (N = 19) were conducted. This study showed that information nudges and high-touch nudges enjoyed the highest level of acceptance. A strong correlation was also found between “most irritating” and group “manipulative” nudges. These forms of nudging fluctuated around the borderline value of acceptance. A strong or moderate correlation was also found between nudges with similar content and different forms. Structured interviews showed that experts supported the use of nudges. They considered it an important tool to influence the study’s success. Experts explained the differences in the acceptance of nudges in connection with the different ages of students, the type of study, the students’ life experiences, and partly with the type of field of study. They considered parents’ education rather ambivalent.
Finding digital solutions in pandemic times: the case of appointment procedures for professors at German universities
Authors: Gerchen Anna
Published: July 2023

In higher education and beyond, the Covid-19 pandemic is considered to have accelerated digitalisation. While this acceleration is usually viewed in the context of the digital transformation that is characterised by its longevity, the permanence of pandemic-driven digitalisation requires investigation. Focusing on appointment procedures for professors as a central element of universities’ governance, the qualitative study presented here employed expert interviews and group discussions to investigate how German universities responded to the challenges of the Covid-19 pandemic by furthering digitalisation. Drawing on the concept of synchronous and asynchronous communication and Luhmann’s understanding of decision programmes, this article proposes differentiating between two modes of digitalisation in order to systematise the empirical findings and thus analytically distinguish pandemic-driven digitalisation from the general digital transformation. It finds that not all of the newly implemented digital solutions will be used permanently and argues that this can be understood in terms of obstructed decision programmes.
Development and Pre-Feasibility Testing of SPECIFiC: A Psychoeducation Programme for Caregivers of Children with Fetal Alcohol Spectrum Disorder (FASD)
Authors: Price Alan D. , Mukherjee Raja A. S. , Webster Anna , Tate David , Allely Clare S. , Brown Sarah , Buckard Joanna , Burd Larry , Butcher Sandra , Shields Jennifer , Cook Penny A.
Published: July 2023

A growing number of evidence-based services are available for fetal alcohol spectrum disorder (FASD), but few focus on caregiver psychoeducation. Despite new guidance in the UK requiring FASD services, the evidence base for effective interventions is currently lacking. An FASD caregiver training program would be a novel and valuable addition to service provision. SPECIFiC (Salford parents and carers education course for improvements in FASD outcomes in children) was developed using an evidence-based logic model with input from clinicians, families, and the charity sector. The course was delivered online to a small number (n = 9) of families in a mixed-methods, exploratory pre-feasibility study. Families were represented by either one or two caregivers, all of whom were adoptive parents or special guardians of a child with FASD. Parent perceptions were assessed using semi-structured interviews. The performance of proposed outcome measures (stress, psychological functioning, parenting self-efficacy, knowledge of FASD, and child behavioral difficulties) was evaluated. Pre- and post-measures were acceptable and showed promise as outcome measures for a future trial. Participants spoke positively about the course, welcomed the opportunity to discuss their own situations with other FASD caregivers, found the advice to be immediately useful, and described the course as therapeutic. Suggestions for improvements tended to focus on timing and technical issues. Based on a small sample, SPECIFiC was shown to be an acceptable and feasible psychoeducation program. Further evidence from a randomized controlled trial is needed to evaluate whether SPECIFiC can lead to reduced stress in parents, improved parenting self-efficacy, and ultimately a reduction in children’s behavioral difficulties.
An Evolution Model for Polygonal Tessellations as Models for Crack Networks and Other Natural Patterns
Authors: Bálint Péter , Domokos Gábor , Regős Krisztina
Published: July 2023

We introduce and study a general framework for modeling the evolution of crack networks. The evolution steps are triggered by exponential clocks corresponding to local micro-events, and thus reflect the state of the pattern. In an appropriate simultaneous limit of pattern domain tending to infinity and time step tending to zero, a continuous time model, specifically a system of ODE is derived that describes the dynamics of averaged quantities. In comparison with the previous, discrete time model, studied recently by two of the present three authors, this approach has several advantages. In particular, the emergence of non-physical solutions characteristic to the discrete time model is ruled out in the relevant nonlinear version of the new model. We also comment on the possibilities of studying further types of pattern formation phenomena based on the introduced general framework.
A multilevel study of peer victimization and its associations with teacher support and well-functioning class climate
Authors: Thornberg Robert , Wänström Linda , Sjögren Björn , Bjereld Ylva , Edling Silvia , Francia Guadalupe , Gill Peter
Published: July 2023

The aim of the current study was to examine whether students’ perceptions of teacher support at an individual-level, teacher support and well-functioning class climate at classroom-level, and teacher support and well-functioning class climate at school-level were associated with peer victimization. Data were obtained from a Student School Survey administered by the selected Swedish municipality. Multilevel analyses were based on 5,646 students in 277 classes and 27 schools. At the individual-level, girls and students who perceived greater teacher support than their classmates were victimized less often by their peers. In addition, students in schools with classes characterized by greater cooperation, cohesion, working atmosphere and respect toward their teachers tended to score lower on peer victimization. Within schools, students belonging to classes with a more well-functioning class climate than what was average in the school, and students belonging to classes that scored their teacher as more caring, fair and respectful compared to other classes in the school, were less likely to be targets of peer victimization.
A point mass proposal method for Bayesian state-space model fitting
Authors: Llewellyn Mary , King Ruth , Elvira Víctor , Ross Gordon
Published: July 2023

State-space models (SSMs) are commonly used to model time series data where the observations depend on an unobserved latent process. However, inference on the model parameters of an SSM can be challenging, especially when the likelihood of the data given the parameters is not available in closed-form. One approach is to jointly sample the latent states and model parameters via Markov chain Monte Carlo (MCMC) and/or sequential Monte Carlo approximation. These methods can be inefficient, mixing poorly when there are many highly correlated latent states or parameters, or when there is a high rate of sample impoverishment in the sequential Monte Carlo approximations. We propose a novel block proposal distribution for Metropolis-within-Gibbs sampling on the joint latent state and parameter space. The proposal distribution is informed by a deterministic hidden Markov model (HMM), defined such that the usual theoretical guarantees of MCMC algorithms apply. We discuss how the HMMs are constructed, the generality of the approach arising from the tuning parameters, and how these tuning parameters can be chosen efficiently in practice. We demonstrate that the proposed algorithm using HMM approximations provides an efficient alternative method for fitting state-space models, even for those that exhibit near-chaotic behavior.