bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms with papillary thyroid carcinoma: A case–control study
Authors: Saljooghi Shaghayegh , Heidari Zahra , Saravani Mohsen , Rezaei Mahnaz , Salimi Saeedeh
Published: December 2022

Background

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer which its precise etiology remains unknown. However, environmental and genetic factors contribute to the etiology of PTC. Axis inhibition protein 1 (Axin1) is a scaffold protein that exerts its role as a tumor suppressor. In addition, Cathepsin B (Ctsb) is a cysteine protease with higher expression in several types of tumors. Therefore, the aim of this study was to investigate the possible association of AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms with PTC susceptibility.

Materials & Methods

In total, 156 PTC patients and 158 sex‐, age‐, and BMI‐matched control subjects were enrolled in the study. AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms were genotyped using the PCR–RFLP method.

Results

There was a relationship between AXIN1 rs12921862 C/A polymorphism and an increased risk of PTC in all genetic models except the overdominant model. The AXIN1 rs1805105 G/A polymorphism was associated with an increased PTC risk only in codominant and overdominant models. The frequency of AXIN1 Ars12921862 Ars1805105 haplotype was higher in the PTC group and also this haplotype was associated with an increased risk of PTC. Moreover, the AXIN1 rs12921862 C/A polymorphism was not associated with PTC clinical and pathological findings, but AXIN1 rs1805105 G/A polymorphism was associated with almost three folds of larger tumor size (≥1 cm). There was no association between CTSB rs12898 G/A polymorphism and PTC and its findings.

Conclusion

The AXIN1 rs12921862 C/A and rs1805105 G/A polymorphisms were associated with PTC. AXIN1 rs1805105 G/A polymorphism was associated with higher tumor size.
Patterns and predictors of material hardship among poor families with children
Authors: Marçal Katherine E.
Published: December 2022

Experiences of material hardship vary across poor families, but little is understood about this variability. The present study aimed to distinguish subtypes of material hardship as well as which characteristics predict subtypes. Latent class analysis with data from a large, longitudinal study of families with youth children investigated subtypes of material hardship as well as predictors of subtypes. Multinomial logistic regression then predicted class membership used on known housing risk factors maternal IPV victimization, depression, and substance use. Analyses identified three distinct subtypes of material hardship: “Housing Insecure,” “Food Insecure,” and “Cost‐Burdened but Managing.” Maternal IPV victimization and depression reduced likelihood of membership in the “Managing” class, but no predictors distinguished families who become food versus housing insecure. Findings suggest widespread financial stress and complex tradeoffs for low‐income families, who struggle to afford basic needs. Maternal safety and mental health prove crucial to families' coping abilities. Increased systemic supports targeting specific circumstances may promote stability and prevent more severe hardship.
Contamination of bacterial extracellular vesicles (bEVs) in human urinary extracellular vesicles (uEVs) samples and their effects on uEVs study
Authors: Noonin Chadanat , Peerapen Paleerath , Thongboonkerd Visith
Published: December 2022

Bacterial overgrowth is common for improperly stored urine. However, its effects on human urinary extracellular vesicles (uEVs) study had not been previously examined nor documented. This study investigated the presence of bacterial EVs (bEVs) contaminated in uEVs samples and their effects on uEVs study. Nanoscale uEVs were isolated from normal human urine immediately after collection (0‐h) or after 25°C‐storage with/without preservative (10 mM NaN3) for up to 24‐h. Turbidity, bacterial count and total uEVs proteins abnormally increased in the 8‐h and 24‐h‐stored urine without NaN3. NanoLC‐ESI‐LTQ‐Orbitrap MS/MS identified 6–13 bacterial proteins in these contaminated uEVs samples. PCR also detected bacterial DNAs in these contaminated uEVs samples. Besides, uEVs derived from 8‐h and 24‐h urine without NaN3 induced macrophage activation (CD11b and phagocytosis) and secretion of cytokines (IFN‐α, IL‐8, and TGF‐β) from macrophages and renal cells (HEK‐293, HK‐2, and MDCK). All of these effects induced by bacterial contamination were partially/completely prevented by NaN3. Interestingly, macrophage activation and cytokine secretion were also induced by bEVs purified from Escherichia coli. This study clearly shows evidence of bEVs contamination and their effects on human uEVs study when the urine samples were inappropriately stored, whereas NaN3 can partially/completely prevent such effects from the contaminated bEVs.
Inhibition of HIST1H2AB suppresses the proliferation of lung adenocarcinoma
Authors: Chai Xiaojun , Wang Guangxue , Hong Xuan , Feng Minghao , Wang He , Liu Fabing , Yao Wei , Zhu Dongyi , Li Qinchuan
Published: December 2022

Background

Lung adenocarcinoma is one of the common causes of cancer‐related deaths worldwide. Histone cluster 1 H2A family member b (HIST1H2AB) is a member of the histone H2A family. Bioinformatic analyses have revealed that HIST1H2AB is highly expressed in some cancers and might be an oncogene. However, information on the function of HIST1H2AB in lung adenocarcinoma is limited.

Methods

The expression of HIST1H2AB was analyzed in normal lung, lung adenocarcinoma and paracancerous tissues from The Cancer Genome Atlas (TCGA) database and immunohistochemistry staining. It was further verified in the relative cell lines using real‐time quantitative polymerase chain reaction (RT‐qPCR). When the adenocarcinoma cells lines (A549 and H1299) were successfully transfected with shHIST1H2AB or an empty plasmid packaged into a lentivirus, cell proliferation was detected using Celigo fluorescence cell‐counting, colony formation and annexin V‐allophycocyanin assays. Twenty nude mice were subcutaneously injected with A549 cells transfected with shHIST1H2AB or empty plasmid; the tumor size was recorded on day 25 and then measured every 3 days thereafter. The final tumor weight was measured on day 37. Significantly differentially expressed genes were analyzed using a human gene expression array. Furthermore, the potentially relevant genes were verified using RT‐qPCR and western blotting.

Results

HIST1H2AB was highly expressed in lung adenocarcinoma tissues from TCGA database and immunohistochemistry staining. Similar results were seen in the lung adenocarcinoma cells. When the cells were successfully transfected with shHIST1H2AB or an empty plasmid, downregulation of HIST1H2AB inhibited the growth and promoted the apoptosis of lung adenocarcinoma cells. The xenograft results suggested that HIST1H2AB downregulation delayed tumor growth and reduced tumor weight. Moreover, interferon signaling pathway and four genes (HMGB1, FOXM1, F2RL1 and SLC4A7) might be regulated by HIST1H2AB in the development of lung adenocarcinoma as indicated through gene expression array, RT‐qPCR and western blotting analyses.

Conclusions

HIST1H2AB acts as an oncogenic protein and HIST1H2AB inhibition suppresses the proliferation of lung adenocarcinoma cells. It may be a novel target for lung adenocarcinoma therapy.
GSK3 inhibitor enhances gemtuzumab ozogamicin‐induced apoptosis in primary human leukemia cells by overcoming multiple mechanisms of resistance
Authors: Inase Aki , Maimaitili Yimamu , Kimbara Shiro , Mizutani Yu , Miyata Yoshiharu , Ohata Shinya , Matsumoto Hisayuki , Kitao Akihito , Sakai Rina , Kawaguchi Koji , Higashime Ako , Nagao Shigeki , Kurata Keiji , Goto Hideaki , Kawamoto Shinichiro , Yakushijin Kimikazu , Minami Hironobu , Matsuoka Hiroshi
Published: December 2022

In acute myeloid leukemia (AML), the heterogeneity of genetic and epigenetic characteristics makes treatment difficult. The prognosis for AML is therefore poor, and there is an urgent need for new treatments for this condition. Gemtuzumab ozogamicin (GO), the first antibody‐drug conjugate (ADC), targets the CD33 antigen expressed in over 90% of AML cases. GO therefore has the potential to counter the heterogeneity of AML patients. However, a major clinical problem is that drug resistance to GO diminishes its effect over time. Here, we report that the inhibition of glycogen synthase kinase 3 (GSK3) alone overcomes several forms of GO resistance at concentrations without antileukemic effects. The GSK3 inhibitors tested significantly enhanced the cytotoxic effect of GO in AML cell lines. We elucidated four mechanisms of enhancement: (1) increased expression of CD33, the target antigen of GO; (2) activation of a lysosomal function essential for hydrolysis of the GO linker; (3) reduced expression of MDR1 that eliminates calicheamicin, the payload of GO; and (4) reduced expression of the anti‐apoptotic factor Bcl‐2. A similar combination effect was observed against patient‐derived primary AML cells. Combining GO with GSK3 inhibitors may be efficacious in treating heterogeneous AML.
Phosphorylation of enteroviral 2Apro at Ser/Thr125 benefits its proteolytic activity and viral pathogenesis
Authors: Wang Yuya , Zou Wenjia , Niu Yan , Wang Sanyuan , Chen Bangtao , Xiong Rui , Zhang Peng , Luo Zhijun , Wu Yong , Fan Changfa , Zhong Zhaohua , Xu Ping , Peng Yihong
Published: December 2022

Enteroviral 2A proteinase (2Apro), a well‐established and important viral functional protein, plays a key role in shutting down cellular cap‐dependent translation, mainly via its proteolytic activity, and creating optimal conditions for Enterovirus survival. Accumulated data show that viruses take advantage of various signaling cascades for their life cycle; studies performed by us and others have demonstrated that the extracellular signal‐regulated kinase (ERK) pathway is essential for enterovirus A71 (EV‐A71) and other viruses replication. We recently showed that ERK1/2 is required for the proteolytic activity of viral 2Apro; however, the mechanism underlying the regulation of 2Apro remains unknown. Here, we demonstrated that the 125th residue Ser125 of EV‐A71 2Apro or Thr125 of coxsackievirus B3 2Apro, which is highly conserved in the Enterovirus, was phosphorylated by ERK1/2. Importantly, 2Apro with phosphor‐Ser/Thr125 had much stronger proteolytic activity toward eukaryotic initiation factor 4GI and rendered the virus more efficient for multiplication and pathogenesis in hSCARB2 knock‐in mice than that in nonphospho‐Ser/Thr125A (S/T125A) mutants. Notably, phosphorylation‐mimic mutations caused deleterious changes in 2Apro catalytic function (S/T125D/E) and in viral propagation (S125D). Crystal structure simulation analysis showed that Ser125 phosphorylation in EV‐A71 2Apro enabled catalytic Cys to adopt an optimal conformation in the catalytic triad His‐Asp‐Cys, which enhances 2Apro proteolysis. Therefore, we are the first to report Ser/Thr125 phosphorylation of 2Apro increases enteroviral adaptation to the host to ensure enteroviral multiplication, causing pathogenicity. Additionally, weakened viruses containing a S/T125A mutation could be a general strategy to develop attenuated Enterovirus vaccines.
Wolf's isotopic response: A case of dermatomal granuloma annulare after COVID‐19 vaccination
Authors: Esfandiari Negar , Benson Patrick , Morley Keith
Published: December 2022

The SARS‐CoV‐2 pandemic was announced in March 2020, with the first vaccines becoming available later that year. Although generally well tolerated, there have been reports of skin reactions occurring after receiving COVID‐19 vaccines, with a rare occurrence of granuloma annulare. Granuloma annulare can occur secondarily to herpes zoster infection in a phenomenon known as Wolf's isotopic response (WIR). WIR has been described to often occur after herpes zoster virus infection, at the location of the healed shingles rash, termed ‘post‐herpetic isotopic response' (PHIR). We present the first reported case of PHIR with granuloma annulare after the Moderna COVID‐19 vaccination series. This reported reaction should not limit receipt of the COVID‐19 vaccine, but awareness of this association can minimise additional work‐up and treatment.
Thermoplastic vulcanizates with an integration of good mechanical performance and excellent resistance to high temperature and oil based on HNBR/TPEE
Authors: Cui Ziwen , Jing Yuanrong , Wang Lin , Liu Yingjun , Du Aihua
Published: December 2022

Thermoplastic vulcanizates (TPVs), with a combination of excellent resilience of conventional elastomer and re‐processibility of thermoplastic, have been widely explored both in academia and industry in recent years. Herein, a new type of thermoplastic vulcanizates with good mechanical performance, excellent resistance to high temperature and oil has been successfully developed based on hydrogenated acrylonitrile butadiene rubber (HNBR) and thermoplastic polyester elastomer (TPEE) by the masterbatch procedure of dynamic vulcanization. The effect of composition ratio of rubber phase/plastic phase (R/P ratio) on the mechanical properties, rheological properties, micromorphology, thermal stability, high temperature‐ and oil‐ resistance of HNBR/TPEE TPV was systematically investigated. The results show that all HNBR/TPEE TPVs exhibit good tensile strength, low hardness, superior stretchability (≥880% elongation at break) and high elasticity (only 13% residual strain when stretched at 50% strain). Interestingly, with the increase in R/P ratio, the hardness of TPVs is decreased linearly and the elasticity increases. Besides, by combining the morphology study and rubber processing analyzer suggest that size of the dispersed rubber phase domains increases significantly as R/P ratio increases, which strengthen the rubber network, creating a better elasticity but reduces the rheological properties of TPVs. In addition, the thermogravimetric analysis shows that the thermal stability of TPV improved with the increase of R/P ratio. HNBR/TPEE TPV shows excellent high temperature‐ and oil‐ resistance after aging which is expected to be used in automotive applications.
Semimechanistic modeling of copeptin and aldosterone kinetics and dynamics in response to rehydration treatment for diabetic ketoacidosis in children
Authors: Otto Marije E. , Burckhardt Marie‐Anne , Szinnai Gabor , Pfister Marc , Gotta Verena
Published: December 2022

Diabetic ketoacidosis (DKA), a frequent complication of type 1 diabetes (T1D), is characterized by hyperosmolar hypovolemia. The response of water‐regulating hormones arginine vasopressin (AVP; antidiuretic hormone) and aldosterone to DKA treatment in children is not well understood, although they may have potential as future diagnostic, prognostic, and/or treatment monitoring markers in diabetic patients. We aimed to characterize the dynamics of the response in copeptin (marker for AVP) and aldosterone secretion to rehydration treatment in pediatric patients with DKA. Data originated from a prospective, observational, multicenter study including 28 pediatric T1D patients treated for DKA (median age, 11.5 years; weight, 35 kg). Serial measurements of hormone levels were obtained during 72 h following rehydration start. Semimechanistic pharmacometric modeling was used to analyze the kinetic/dynamic relationship of copeptin and aldosterone secretion in response to the correction of hyperosmolality and hypovolemia, respectively. Modeling revealed different sensitivities for osmolality‐dependent copeptin secretion during the first 72 h of rehydration, possibly explained by an osmotic shift introduced by hypovolemia. Response in aldosterone secretion to the correction of hypovolemia seemed to be delayed, which was well described by an extra upstream turnover compartment, possibly representing chronic upregulation of aldosterone synthase (cytochrome P450 11B2). In conclusion, semimechanistic modeling provided novel physiological insights in hormonal water regulation in pediatric patients during DKA treatment, providing rationale to further evaluate the potential of monitoring copeptin, but not aldosterone due to its delayed response, for future optimization of rehydration treatment to reduce the risk of acute complications such as cerebral edema.
Management practice and soil properties affect plant productivity and root biomass in endophyte‐symbiotic and endophyte‐free meadow fescue grasses
Authors: Keronen Sanna , Helander Marjo , Saikkonen Kari , Fuchs Benjamin
Published: December 2022

Introduction

Pesticides are increasingly used in intensely managed agro‐environments, with an increasingly acknowledged impact on crop production, root establishment and plant resilience. At the same time management practices are intensified with the goal to maximize productivity.

Materials and Methods

In a greenhouse, we studied the effects of three mowing regimes (uncut, and cutting 5 or 15 cm) employed three times during the season on root and shoot biomass and chlorophyll content of the cool‐season grass Festuca pratensis (meadow fescue) growing in soil with a history of glyphosate‐based herbicide (GBH) use, the corresponding control soil, and sterilized control soil. Half of the plants hosted a systemic and vertically transmitted fungal endophyte, Epichloë uncinata, which is known to promote host grass growth.

Results

Endophyte symbiosis did not affect any tested plant parameters. Cutting the plants to 5 cm decreased both root and cumulative shoot biomass. Herbicide soil history, together with intense cutting (5 cm), caused a decrease in shoot biomass and lowered the chlorophyll content. Surprisingly, soil sterilization boosted shoot biomass and chlorophyll concentrations during less intense cutting (15 cm) and noncutting when compared to the control soil. Root biomass reduced in uncut plants when growing in soil with a history of glyphosate use.

Conclusion

Our results indicate that GBH residues in the soil can diminish shoot biomass when grass is frequently cut. Decreased root biomass caused by soil glyphosate history goes together with a reduction of carbon allocation belowground, which decreases grassland resilience to climate warming, increasingly occurring droughts and extreme weather events.
Detection of Glucose Based on Noble Metal Nanozymes: Mechanism, Activity Regulation, and Enantioselective Recognition
Authors: Chen Jiaqi , Liu Xiaoyang , Zheng Guangchao , Feng Wei , Wang Pan , Gao Jian , Liu Jianbo , Wang Mingzhe , Wang Qingyuan
Published: December 2022

Glucose monitoring is essential to evaluate the degree of glucose metabolism disorders. The enzymatic determination has been the most widely used method in glucose detection because of its high efficiency, accuracy, and sensitivity. Noble metal nanomaterials (NMs, i.e., Au, Ag, Pt, and Pd), inheriting their excellent electronic, optical, and enzyme‐like properties, are classified as noble metal nanozymes (NMNZs). As the NMNZs are often involved in two series of reactions, the oxidation of glucose and the chromogenic reaction of peroxide, here the chemical mechanism by employing NMNZs with glucose oxidase (GOx) and peroxidase (POD) mimicking activities is briefly summarized first. Subsequently, the regulation strategies of the GOx‐like, POD‐like and tandem enzyme‐like activities of NMNZs are presented in detail, including the materials, size, morphology, composition, and the reaction condition of the representative NMs. In addition, in order to further mimic the enantioselectivity of enzyme, the design of NMNZs with enantioselective recognition of d‐glucose and l‐glucose by using different chiral compounds (DNA, amino acids, and cyclodextrins) and molecular imprinting is further described in this review. Finally, the feasible solutions to the existing challenges and a vision for future development possibilities are discussed.
Hot Working Tool Steel with Bainitic Microstructure—The Mechanical Properties at Elevated Temperature
Authors: Krull Hans-Günter , van Soest Frank , Niederhofer Philipp , Schneiders Till
Published: December 2022

Usually, tool steels are used in quenched and tempered conditions. Due to the phase transition from austenite to martensite and the volume change during the transformation, controlling distortion might be challenging. A newly developed steel focusing on a bainitic structure, even for bigger dimensions, shows a lower hardness at ambient temperature than conventional hot working tool steels but with a lower temperature dependency. Therefore, at service temperature, the mechanical properties are comparable to established grades. Heat treatment is simplified by a simple austenitization and cooling process without special requirements on the cooling rate. Due to a generally lower cooling rate and lower hardness compared to a quench and tempering process, the risk of cracking is reduced while machinability is improved. With the combination of good weldability and rather low hardness after rapid cooling, this grade can also be processed in additive manufacturing and is well suited for a hybrid process of conventional and additive manufacturing.
Structure prediction via global energy landscape exploration of the ternary rare‐earth compound LaOI
Authors: Pejić M. , Zagorac D. , Zagorac J. , Matović B. , Schön J. C.
Published: December 2022

Crystal structure prediction has been performed via the global exploration of the energy landscape of lanthanum oxyiodide (LaOI), using simulated annealing and involving over one million local optimizations. Afterwards, the most promising structure candidates among the minima found were subjected to local optimizations onab initiolevel. Density functional theory (DFT) calculations were performed, using the GGA‐PBE functional, together with the hybrid HSE06 exchange‐correlation functional. Seven most relevant low‐energy minima were found after the finalab initiorelaxation. The global minimum found corresponds to the α‐LaOI tetragonal structure in agreement with previous experimental and theoretical reports. The prediction of the additional β‐, γ‐, δ‐, ϵ‐, ζ‐, and η‐LaOI modifications demonstrate the rich diversity of local cation‐anion coordinations and structure types ranging from cubic and tetragonal, over rhombohedral and orthorhombic to monoclinic symmetry. Moreover, there are many previous experimental reports on related structures in the lanthanide oxyfluorides, which might guide possible future syntheses of LaOI‐modifications. A successful synthesis of these novel LaOI materials could have multiple technological applications ranging from nano‐ and bio‐materials to medicine, solid oxide fuel cells and photocatalytic materials.
The Dissipation Properties of Transport Noise
Authors: Flandoli Franco , Luongo Eliseo
Published: December 2022

The aim of this work is to present, in a compact way, the latest results about the dissipation properties of transport noise in fluid mechanics. Starting from the reasons why transport noise is natural in a passive scalar equation for the heat diffusion and transport, several results about enhanced dissipation due to the noise are presented. Rigorous statements are matched with numerical experiments in order to understand that the sufficient conditions stated are not yet optimal but give a first useful indication.
Erste Schritte zur automatisierten Generation von Items in einem webbasierten Tracingsystem
Authors: Bastian Morten , Mühling Andreas
Published: December 2022

Der Beitrag stellt die Ergebnisse einer Vorstudie und einer experimentellen Studie (N = 273) in der Sekundarstufe und der Universität im Kontext der Programmierung, genauer der Programmablaufverfolgung (Tracing), vor. Das Ziel ist die automatische Generierung von Items in einem adaptiven Testsystem, die bekannte Fehlvorstellungen sichtbar machen können. Verglichen werden dazu zunächst die empirisch unter Lernenden ermittelten Schwierigkeiten bekannter Items mit den Schwierigkeiten, die aus einem theoretischen Vorhersagemodell abgeleitet werden, sowie mit einem Rating von Experten. Darauf aufbauend werden Items anhand von einfachen Regeln generiert und in einer Hauptstudie deren durch die Regeln vorhergesagte Schwierigkeitsrangfolge empirisch überprüft. Die Ergebnisse zeigen, dass eine solche regelbasierte Generierung von Items vielversprechend ist. Bestimmte Programmkonstrukte sind hinsichtlich ihrer Schwierigkeit auf diese Weise gut klassifizierbar und können so für die automatisierte Itemkonstruktion genutzt werden. Praktisch erlauben solche adaptiven Testverfahren in kurzer Zeit die Diagnose von Fehlvorstellungen, die eine große Hürde in der Programmierausbildung darstellen. Aufgrund der Regeln und des Itemformats ist es darüber hinaus möglich, gezielt Feedback zu den Fehlvorstellungen an die Testerinnen und Tester, oder auch die Lernenden selbst, zu geben.
On Loops in Water Wave Branches and Monotonicity of Water Waves
Authors: Kozlov Vladimir
Published: December 2022

We give a quite simple approach how to prove the absence of loops in bifurcation branches of water waves in rotational case with arbitrary vorticity distribution. The supporting flow may contain stagnation points and critical layers and water surface is allowed to be overhanging. Monotonicity properties of the free surface are presented. Especially simple criterium of absence of loops is given for bifurcation branches when the bifurcation parameter is the water wave period. We show that there are no loops if you start from a water wave with a positive/negative vertical component of velocity on the positive half period.
Transparenz in der klinischen Forschung: Welchen Beitrag leistet die neue EU-Verordnung 536/2014?
Authors: Strech Daniel
Published: December 2022

Klinische Studien können in 4 Bereichen mehr oder weniger transparent sein: A) Studienregistrierung, B) Ergebnisveröffentlichung, C) Teilen von Daten und Codes, D) studienbezogene Dokumente. Dieser Diskussionsbeitrag erläutert, in welcher Ausprägung die EU-Verordnung 536/2014 (Clinical Trials Regulation – CTR) den Bereich Ergebnisveröffentlichung bei interventionellen Arzneimittelstudien nachweisbar positiv beeinflusst hat und wie sie die Verfügbarkeit studienbezogener Dokumente für unabhängige Forschung in Zukunft verbessern kann.

Da der positive Trend aktuell nur im Bereich Ergebnisveröffentlichung auszumachen ist und zudem nur bei der Subgruppe interventioneller Arzneimittelstudien, scheint sich eine „2-Klassen-Transparenz“ zu entwickeln, die zwischen Studien gemäß CTR und den übrigen Studien unterscheidet. Unabhängig von der CTR sollten sich deshalb akademische Einrichtungen, Förderer und Ethikkommissionen mit der besseren Umsetzung aller 4 Transparenzbereiche beschäftigen und dies bei allen klinischen Studien. Ein Monitoring zur Umsetzung der Transparenz bei klinischen Studien wäre ein wichtiger erster Schritt, um den Handlungsbedarf zu konkretisieren. Eine Neuerung im Kontext Transparenz klinischer Studien könnte sich zudem dadurch ergeben, dass das neue EU-Portal „Clinical Trials Information System“ (CTIS) gemäß CTR studienbezogene Dokumente zur informierten Einwilligung (Informed Consent), Studienprotokolle und Prüferinformationen (Investigator Brochures) transparenter machen soll. Damit ergäbe sich erstmals die Möglichkeit einer unabhängigen Forschung und Qualitätssicherung zu Fragen der informierten Einwilligung und der Nutzen-Schaden-Abwägung bei klinischen Studien.
Verruköser exophytischer Tumor der Glans penis
Authors: Aebischer Valentin , Forchhammer Stephan
Published: December 2022

Ein 59-jähriger Patient stellte sich mit einem seit 1 Jahr wachsenden Tumor an der Glans penis vor, den wir exzidierten. Histologisch zeigte sich eine akanthotische Epidermis, unter der die Papillarkörper prall angefüllt waren mit zahlreichen schaumigen Histiozyten. Der Befund entspricht einem verruziformen Xanthom. Die Differenzialdiagnose eines Peniskarzinoms erfordert eine deutlich radikalere Therapie. Da mutilierende Penisoperationen mit erheblichen psychosexuellen Belastungen für die Patienten einhergehen, kann die Kenntnis dieser gutartigen Diagnose einem vorschnell aggressiven Vorgehen bei ähnlichen Tumoren vorbeugen und zu bedachtem Vorgehen anregen.
Heating of Large Endovascular Stents and Stent Grafts in Magnetic Particle Imaging—Influence of Measurement Parameters and Isocenter Distance
Authors: Wegner Franz , von Gladiss Anselm , Wei Huimin , Behrends André , Grzyska Ulrike , Sieren Malte M. , Haegele Julian , Graeser Matthias , Buzug Thorsten M. , Barkhausen Joerg , Friedrich Thomas
Published: December 2022

Purpose

Magnetic particle imaging (MPI) is a tomographic imaging modality with the potential for cardiovascular applications. In this context, the extent to which stents are heated should be estimated from safety perspective. Furthermore, the influence of the measurement parameters and stent distance to the isocenter of the MPI scanner on stent heating were evaluated.

Materials and Methods

Nine different endovascular stents and stent grafts were tested in polyvinyl-chloride tubes. The stents had diameters from 10 to 31 mm, lengths between 25 and 100 mm and were made from stainless steel, nitinol or cobalt-chromium. The temperature differences were recorded with fiber-optic thermometers. All measurements were performed in a preclinical commercial MPI scanner. The measurement parameters were varied (drive field strengths: 3, 6, 9, 12 mT and selection field gradients: 0, 1.25 and 2.5 T/m). Furthermore, measurements with different distances to the scanner’s isocenter were performed (100 to 0 mm).

Results

All stents showed heating (maximum 53.1 K, minimum 4.6 K). The stent diameter directly correlated with the temperature increase. The drive field strength influenced the heating of the stents, whereas the selection field gradient had no detectable impact. The heating of the stents decreased with increasing distance from the scanner’s isocenter and thus correlated with the loss of the scanner’s magnetic field.

Conclusion

Stents can cause potentially harmful heating in MPI. In addition to the stent diameter and design, the drive field strength and the distance to the MPI scanner’s isocenter must be kept in mind as influencing parameters.
Prediction of incident cardiovascular events using machine learning and CMR radiomics
Authors: Pujadas Esmeralda Ruiz , Raisi-Estabragh Zahra , Szabo Liliana , McCracken Celeste , Morcillo Cristian Izquierdo , Campello Víctor M. , Martín-Isla Carlos , Atehortua Angelica M. , Vago Hajnalka , Merkely Bela , Maurovich-Horvat Pal , Harvey Nicholas C. , Neubauer Stefan , Petersen Steffen E. , Lekadir Karim
Published: December 2022

Objectives

Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), and stroke using machine learning techniques.

Methods

We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.

Results

AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.

Conclusions

Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.

Key Points

• Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques.

• CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models.

• The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.
Tear film layers and meibomian gland assessment in patients with type 1 diabetes mellitus using a noninvasive ocular surface analyzer: a cross-sectional case–control study
Authors: Silva-Viguera María-Carmen , Pérez-Barea Alicia , Bautista-Llamas María-José
Published: December 2022

Purpose

To assess the tear film layers and Meibomian glands by a noninvasive ocular surface analyzer in patients with and without type 1 diabetes mellitus (T1DM).

Methods

Eighty-eight participants were enrolled in this study: 44 patients with T1DM without diabetic retinopathy, and 44 patients as a control group, between 18 and 49 years old. Limbal and bulbar redness classification, lipid layer thickness (LLT), tear meniscus height (TMH), first and mean noninvasive tear break-up time (FNIBUT and MNIBUT, respectively), and Meibomian glands loss (MGL) were assessment through the ICP Ocular Surface Analyzer (OSA). Schirmer’s I test (SIT), the fluorescein tear break-up time test (TFBUT), OSDI and SPEED questionnaires, and percentage of glycosylated hemoglobin (HbA1c) were also tested.

Results

The T1DM group showed higher limbal and bulbar redness (p = 0.010) and lower LLT (p < 0.001), TMH (p < 0.001), FNIBUT (p < 0.001), MNIBUT (p < 0.001), SIT (p = 0.001), and TFBUT (p < 0.001) than the control group. A higher percentage of MGL was found in the T1DM group in the upper (p = 0.097) and lower (p < 0.001) eyelids. No significant differences were found in dry eye symptoms across the OSDI and SPEED questionnaires between the two groups.

Conclusion

Patients with T1DM without signs of retinopathy showed involvement of the mucoaqueous and lipid layers of the tear film, as well as a higher percentage of MGL, using a noninvasive analyzer. Dry eye disease in people with T1DM cannot be ruled out by anamnesis and subjective symptom questionnaires alone; therefore, these patients should undergo regular anterior pole examinations.
Food intolerances in children and adolescents in Switzerland
Authors: Légeret Corinne , Lohmann Clarissa , Furlano Raoul I. , Köhler Henrik
Published: December 2022

Adverse food reactions have become an important health concern in pediatrics. There are discrepancies between diagnosed and self-reported food allergies and intolerances, leading to food avoidance with possible psychological and nutritional implications in the latter. There is no data available so far on the number of children and adolescents, who reduce or completely avoid certain foods in their diet. The aim of this study was to determine the prevalence of children and adolescents in the Northwest of Switzerland, who omit foods from their diet because of a self-reported intolerance, as well as the prevalence of children and adolescents who eliminate well-tolerated foods for presumed health reasons. This is a cross-sectional study conducted in the Children’s hospitals of Aarau and Basel (Switzerland) and in 4 pediatric private practices. A total of 2036 children and adolescents (54% male and 46% female) between 1 month and 18 years (mean age: 7.4 years) were included, of which 316 (16%) participants reported to avoid foods due to intolerance. Lactose intolerance is the most frequent one. In 55% of all cases, no medical tests had been performed to confirm such an intolerance. Avoiding tolerated foods for presumed health reasons was stated by 251 (12%) participants.

  Conclusions: Clinicians should be aware of the high frequency of food avoidance in the pediatric population due to true intolerance, functional diseases, or due to lifestyle reasons. Milk is the most avoided food and half of the affected patients avoid foods without guidance by professional dieticians, therefore risking possible negative impacts on their physical and mental health. Pediatricians should perform further investigations or advise nutritional guidance if an avoidance of foods or specific diets occurs.

What is Known:• The prevalence of food intolerances in children and adolescents is unknown.• Eating behavior in children is influenced by the consumption of social media.

What is New:• Based on this large cross-sectional study, it was shown that 16% of children and adolescents avoid foods, half of them without any medical advice.• Food avoidance is common among this Swiss cohort of children because of different reasons: lifestyle habits, functional diseases, true intolerances with possible consequences such as micronutrient deficiencies if not properly monitored.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal surface malignancies (PSM): a prospective single-center registry study
Authors: Jansen-Winkeln B. , Eberth J. , Moulla Y. , Mehdorn M. , Niebisch S. , Schierle K. , Bläker H. , Lordick F. , Gockel I. , Thieme R.
Published: December 2022

Purpose

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new, palliative approach for patients with peritoneal surface malignancies (PSMs). Its main goals are to control symptoms and ascites. For this experimental procedure, treatment efficacy and patient safety need to be closely monitored.

Methods

We performed a prospective registry study for patients with PSMs. Cisplatin (C) (7.5 mg/m2 body surface) and doxorubicin (D) (1.5 mg/m2) were administered laparoscopically via PIPAC.

Results

Between November 2015 and June 2020, we recorded data from 108 patients and 230 scheduled procedures. Tumor burden, patient fitness, quality of life, operating time and in-hospital stay remained stable over consecutive procedures. We recorded 21 non-access situations and 14 intraoperative complications (11 intestinal injuries, and three aspirations while inducing anesthesia). Three or more previous abdominal surgeries or cytoreductive surgery (CRS) with intraperitoneal hyperthermic chemoperfusion (HIPEC) were risk factors for non-access and intestinal injuries (χ2, p ≤ 0.01). Five Grade IV and three Grade V postoperative complications according to the Clavien–Dindo Classification (CDC) occurred. Median overall survival was 264 days (interquartile range 108–586). Therapies were primarily discontinued because of death (34%), progressive (26%), or regressive (16%) disease.

Conclusion

PIPAC is effective in stabilizing PSMs and retaining quality of life in selected patients. Earlier abdominal surgeries and CRS with HIPEC should be considered when determining the indication for PIPAC. Randomized controlled studies are needed to evaluate PIPAC’s therapeutic benefits compared to systemic chemotherapy (sCHT) alone.

Trial registration

NCT03100708 (April 2017).
‘It made me feel part of the team, having my homework to do’ — women and specialist nurse experiences of remote follow-up after ovarian cancer treatment: a qualitative interview study
Authors: Kennedy Fiona , Shearsmith Leanne , Holmes Marie , Velikova Galina
Published: December 2022

Purpose

Ovarian cancer patients require monitoring for relapse post-treatment, and alternative follow-up pathways are increasing, which require in-depth exploration to ensure acceptability and inform implementation. This study aimed to explore women and specialist nurses’ experiences of participating in a feasibility study of an electronic patient-reported outcome (ePRO) follow-up pathway after ovarian cancer treatment.

Methods

The feasibility study incorporated an ePRO questionnaire, blood test and telephone consultation with a specialist nurse, instead of face-to-face hospital visits. All women and the nurses involved were invited to take part in nested semi-structured interviews. Interviews were recorded and transcripts analysed using framework analysis.

Results

Twenty interviews were conducted (16 out of 24 women who took part in the feasibility study and all 4 nurses). Four themes were identified: (1) readiness and motivators, (2) practicalities and logistics, (3) personal impact and (4) future role. An overarching theme highlighted how women strived to seek reassurance and gain confidence. Most women and nurses were positive about the ePRO pathway and would happily continue using it.

Conclusion

This work provides invaluable insight into the experiences of women on remote ePRO follow-up post-treatment. Important logistic and implementation issues were identified, which should inform future large-scale work to introduce and evaluate remote ePRO methods in cancer follow-up. This work highlights the key factors influencing women’s readiness and acceptability of an ePRO pathway, and how services should be carefully designed to ensure patients feel reassured and confident post-treatment. Furthermore, it highlights that flexibility and patient preference should be considered in remote service delivery.

Trial registration

ClinicalTrials.gov ID: NCT02847715 (first registered 19 May 2016).
High-field/High-frequency EPR Spectroscopy in Protein Research: Principles and Examples
Authors: Möbius Klaus , Savitsky Anton
Published: December 2022

During the last decades, the combined efforts of biologists, chemists, and physicists in developing high-field/high-frequency EPR techniques and applying them to functional proteins have demonstrated that this type of magnetic resonance spectroscopy is particularly powerful for characterizing the structure and dynamics of stable and transient states of proteins in action on biologically relevant time scales ranging from nanoseconds to hours. The review article describes how high-field EPR methodology, in conjunction with site-specific isotope and spin-labeling strategies, is capable of providing new insights into fundamental biological processes. Specifically, we discuss the theoretical and instrumental background of continuous-wave and pulse high-field EPR and the multiple-resonance extensions EDNMR, ENDOR, TRIPLE, ESEEM, PELDOR, and RIDME. Some emphasis is placed on a balanced description of both the historical spadework and the achieved performance of advanced EPR at 95 GHz and 360 GHz. This culminates in a coherent treatment of state-of-the-art research of high-field EPR in terms of both instrumentation development and application to representative protein complexes such as cofactor binding sites in photosynthesis.
Säuglings‑, Kinder- und Jugendlichen- (SKJ) Psychotherapien während der Covid-19 Pandemie: Ergebnisse einer Studie unter psychodynamischen Psychotherapeut*innen in Österreich
Authors: Fiala-Baumann Brigitte , Ploner Helga , Witzmann Dominik , Jesser Andrea
Published: December 2022

Fragestellung

Diese explorative Studie untersucht die Situation der Säuglings‑, Kinder- und Jugendlichen- (SKJ) Psychotherapien während der Covid-19 Pandemie in Österreich.

Methodik

23 psychodynamisch arbeitende Psychotherapeut*innen nahmen an einer Online-Umfrage teil, die quantitative und qualitative Daten generierte. Offene Fragen zu subjektiv wahrgenommenen Veränderungen wurden mithilfe der qualitativen Inhaltsanalyse ausgewertet.

Ergebnisse

Insgesamt sank die Anzahl an Psychotherapien insbesondere bei den Säuglings- und Kleinkind-Psychotherapien. Die Zahl der Kinder und Jugendlichen-Psychotherapien nahm zunächst ab, stieg nach dem ersten Lockdown aber an. Große Nachfrage wurde zuletzt vor allem bei Jugendlichenpsychotherapien wahrgenommen. Anpassungsleistungen an sich ändernde Bedingungen und Settings erforderten große Flexibilität der Psychotherapeut*innen, die mit Fortschreiten der Pandemie zunehmend an ihre Belastungsgrenzen kamen. Befragte beobachteten eine Zunahme an Symptomen sowie einen gestiegenen Bedarf an Eltern- und Vernetzungsarbeit mit Institutionen.

Schlussfolgerungen

Tele-Psychotherapie kann vor allem mit jüngeren Kindern Präsenztherapie nicht ersetzen. Ergebnisse deuten auf eine Unterversorgung dieser Zielgruppe hin. Dies, sowie die beobachtete Zunahme an Symptomen bei älteren Kindern und Jugendlichen, ist gesellschaftspolitisch und gesundheitsökonomisch ein großes Thema und erfordert dringend einen weiteren Ausbau der Versorgungsnetzwerke.
Electroconvulsive therapy in children and adolescents: results from a population‑based study utilising the Swedish National Quality Register
Authors: Rask Olof , Nordenskjöld Axel , Johansson Björn Axel , Movahed Rad Pouya
Published: December 2022

Electroconvulsive therapy (ECT) is effective and safe for adults with severe depression, but less studied in adolescents. Here, we examined the indications, prevalence, practice, response and remission rates, and side effects in young people treated with ECT in Sweden. We also examined the usage of ECT in the transition to adult psychiatry. Using data from national patient registers and the Swedish National Quality Register for ECT (Q-ECT), we identified patients aged up to 19 years treated with ECT over a 5-year study period. Response and remission rates were analysed using the Clinical Global Impression (7-point scale)-Improvement (CGI-I) and Severity (CGI-S). A total of 118 individuals were identified, of which 105 were also enrolled in the Q-ECT. The most common indication for ECT was depression (68%; n = 80). Adolescents aged < 18 years were more severely ill before treatment than those aged 18 years (P < 0.01). Three of the hospitals in Sweden treated the majority of adolescents < 18 years old. The median number of sessions in each ECT series was seven. Unilateral placement of the electrodes was the most common (88%; n = 99). Fifty-seven percent (n = 54) of the patients responded (CGI-I, 1–2) to the treatment; remission (CGI-S, 1–2) was achieved by 32% (n = 30). Psychotic symptoms were associated with a higher response rate in patients with depression (P = 0.038). A deterioration of memory compared to pre-treatment was reported in six patients. ECT was associated with high response and remission rates in adolescents with severe psychiatric disorders after non-response to medication.