bluuebunny/crossref_metadata_2025 huggingface dataset:
Network-informed discovery of multidrug combinations for ERα+/HER2-/PI3Kα-mutant breast cancer
Authors: Hany Dina , Zoetemelk Marloes , Bhattacharya Kaushik , Nowak-Sliwinska Patrycja , Picard Didier
Published: March 2023

Breast cancer is a persistent threat to women worldwide. A large proportion of breast cancers are dependent on the estrogen receptor α (ERα) for tumor progression. Therefore, targeting ERα with antagonists, such as tamoxifen, or estrogen deprivation by aromatase inhibitors remain standard therapies for ERα + breast cancer. The clinical benefits of monotherapy are often counterbalanced by off-target toxicity and development of resistance. Combinations of more than two drugs might be of great therapeutic value to prevent resistance, and to reduce doses, and hence, decrease toxicity. We mined data from the literature and public repositories to construct a network of potential drug targets for synergistic multidrug combinations. With 9 drugs, we performed a phenotypic combinatorial screen with ERα + breast cancer cell lines. We identified two optimized low-dose combinations of 3 and 4 drugs of high therapeutic relevance to the frequent ERα + /HER2-/PI3Kα-mutant subtype of breast cancer. The 3-drug combination targets ERα in combination with PI3Kα and cyclin-dependent kinase inhibitor 1 (p21). In addition, the 4-drug combination contains an inhibitor for poly (ADP-ribose) polymerase 1 (PARP1), which showed benefits in long-term treatments. Moreover, we validated the efficacy of the combinations in tamoxifen-resistant cell lines, patient-derived organoids, and xenograft experiments. Thus, we propose multidrug combinations that have the potential to overcome the standard issues of current monotherapies.
Vergleich von Behandlungspfaden beim akuten Schlaganfall – eine qualitative multizentrische Studie in drei zuweisenden Kliniken eines Schlaganfallnetzwerkes
Authors: Herzog Franziska , Sert Melek , Hoffmann Johanna , Stang Christina , Seker Fatih , Purrucker Jan , Wick Wolfgang , Busetto Loraine , Gumbinger Christoph
Published: March 2023

Hintergrund

In Schlaganfallnetzwerken verlegen Kliniken, die selbst keine endovaskuläre Thrombektomie (EVT) durchführen (hier: Primärkliniken), Patient*innen für diese Therapie in spezialisierte Schlaganfallzentren. Zur Verbesserung des Zugangs und des Managements der EVT muss der Fokus der Forschung nicht nur auf den spezialisierten Zentren, sondern auch auf den vorangehenden Prozessen in den Primärkliniken liegen.

Fragestellung

Wie stellen sich die Schlaganfallbehandlungspfade in verschiedenen Primärkliniken dar und was wird in diesen Pfaden als Vor- und Nachteil gesehen?

Methoden

Im Rahmen einer qualitativen multizentrischen Studie in drei Primärkliniken eines Schlaganfallnetzwerkes wurde die Versorgung von Schlaganfallpatient*innen mithilfe von nichtteilnehmenden Beobachtungen und 15 leitfadengestützten Interviews mit Beschäftigten unterschiedlicher Professionen erfasst und analysiert.

Ergebnisse

Innerhalb der Schlaganfallbehandlungspfade wurden folgende Aspekte als vorteilhaft berichtet: (1) eine strukturierte und persönliche Ankündigung von Schlaganfallpatient*innen in der Primärklinik durch den Rettungsdienst, (2) ein effizienter Ablauf des Telekonsils, (3) die Notfallverlegung zur EVT durch die gleichen Rettungsdienstmitarbeitenden der Primärzuweisung und (4) die Integration von externen Neurolog*innen in klinikinterne Strukturen.

Diskussion

Die Studie liefert einen Einblick in die z. T. unterschiedlichen Schlaganfallbehandlungspfade drei verschiedener Primärkliniken eines Schlaganfallnetzwerkes. Aus den Ergebnissen lassen sich Verbesserungspotenziale auch für andere Kliniken ableiten. Allerdings ist diese Studie zu klein, um verlässliche Aussagen über deren Wirksamkeit zu geben. Zukünftige Studien sollten daher untersuchen, ob Implementierungen der hier erarbeiteten Empfehlungen tatsächlich zu Verbesserungen führen bzw. unter welchen Bedingungen diese erfolgreich sind. Zur Sicherstellung der Patientenzentrierung sollte dabei auch die Perspektive von Betroffenen und Angehörigen miteinbezogen werden.
ANOVA analysis for estimating the accuracy and surface roughness of precisely drilled holes of steel 42CrMo4 QT
Authors: Řehoř Jan , Fulemová Jaroslava , Kutlwašer Jan , Gombár Miroslav , Harničárová Marta , Kušnerová Milena , Vagaská Alena , Povolný Michal , Valíček Jan , Zatloukal Tomáš
Published: March 2023

The presented publication is focused on increasing the productivity and efficiency of machine production of precision holes. Considerable attention was paid to the influence of the pre-preparation and drilling technology on the quality of the reamed hole. The material selected for machining was chromium-molybdenum steel 42CrMo4 QT. The cluster analysis is implemented to evaluate the experimental results obtained by measuring the cylindricity and surface roughness of the drilled and reamed holes. The factor of hole pre-preparation technology was selected in two quality levels, and the factor of drilling technology in four quality levels. The constant factors were carefully controlled during the experiment, i.e., other possible influences were excluded or minimised. Under constant cutting conditions, the experiment of the subject machining process was carried out. The cutting process parameters investigated were the cylindricity and the roughness of the machined surface Ra. The novelty and contribution of this research lie in confirming the assumption that drilling technology influences hole quality primarily, whereas hole pre-preparation technology has a secondary effect.
Numerical and experimental study to predict the forming process conditions of non-axisymmetric glass perfume bottles
Authors: Biosca Adrià , Borrós Salvador , Clemente Vicenç Pedret , Hyre Matthew R. , Granada Andrés‐Amador García
Published: March 2023

Blow and blow forming process for glass bottle is already validated for 2D axisymmetrical bottles. Current research evaluates the capabilities of the 3D simulations with more complex geometries. This article presents the results of a numerical and experimental study of a non-axisymmetrical glass bottle. In this study, a perfume bottle with a square-based prism geometry and a new set of industrial process conditions have been evaluated. To validate the numerical results, the predicted temperatures in the glass domain have been correlated with experimental infrared measurements of the glass at various stages of the forming process. A comparison of the predicted glass thickness distributions with the section profiles obtained from the manufactured glass bottles is also provided. Finally, transition from the 2 Da to 3D model resulted in new difficulties and capabilities that are also discussed. This study validates simulations with experimental results to help in the design process of molds to avoid undesired thickness distributions and even fracture of glass containers for low thickness 3D corners.
Dramatic effect of the nature of R on the intrinsic acidity and basicity of potential astrochemical R–C≡COH and R–C≡CSH compounds
Authors: Mó Otilia , Alkorta Ibon , Guillemin Jean-Claude , Yáñez Manuel
Published: March 2023

The effect of changing the nature of the R substituent from the first row (H, Li, BeH, BH2, CH3, NH2, OH and F) to second row (Na, MgH, AlH2, SiH3, PH2, SH and Cl) on the intrinsic acidity and basicity of R–C≡COH and R–C≡CSH compounds was investigated through the use of G4 high-levelab initiocalculation. The variation of the acidity and basicity of the R–C≡CSH derivatives as a function of R is practically parallel to that found for the corresponding R–C≡COH analogs; though the basicities of the former are 9–14% higher than those of the latter, the acidity gap being very small (~ 2%). When this analysis is extended to the derivatives in which the triple CC bond is replaced by a double or single bond, it is found that the acidity gap increases systematically as the CC bond goes from triple to single; whereas, as expected for the basicity, the trend is the opposite. Quite surprisingly, however, the variation of the basicity of R–C≡CX (X = OH, SH) compounds with the nature of the first-row substituents, R, is remarkably different from that produced by the second-row analogs. The same is observed as far as intrinsic acidities are concerned. These dissimilarities reflect the rather different changes in the strength of the CC and the CX (X = OH, SH) bonds when a first-row substituent is replaced by the second-row analog, as reflected in the atoms in molecules (AIM), natural bond orbital (NBO) and the electron localization function (ELF) analyses of the corresponding species.
225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings
Authors: Sathekge Mike , Bruchertseifer Frank , Vorster Mariza , Lawal Ismaheel O. , Mokoala Kgomotso , Reed Janet , Maseremule Letjie , Ndlovu Honest , Hlongwa Khanyi , Maes Alex , Morgenstern Alfred , Van de Wiele Christophe
Published: March 2023

Purpose

225Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following 225Ac-PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment and are seeking alternative therapies. Thus, we report our preliminary findings in a retrospective series of 21 mHSPC patients that refused standard treatment options and were treated with 225Ac-PSMA-617.

Methods

We retrospectively reviewed patients with histologically confirmed de novo treatment-naïve bone ± visceral mHSPC that were treated with 225Ac-PSMA-617 radioligand therapy (RLT). Inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, treatment-naive bone ± visceral mHSPC, and patients refusal for ADT ± docetaxel, abiraterone acetate, or enzalutamide. We evaluated the response to treatment using prostate-specific antigen (PSA) response and the progression-free survival (PFS) and overall survival (OS) as well as the toxicities.

Results

Twenty-one mHSPC patients were included in this preliminary work. Following treatment, twenty patients (95%) had any decline in PSA and eighteen patients (86%) presented with a PSA decline of ≥ 50% including 4 patients in whom PSA became undetectable. A lower percentage decrease in PSA following treatment was associated with increased mortality and shorter progression-free survival. Overall, administration of 225Ac-PSMA-617 was well tolerated. The commonest toxicity seen was grade I/II dry mouth observed in 94% of patients.

Conclusions

Given these favorable results, randomized prospective multicenter trials assessing the clinical value of 225Ac-PSMA-617 as a therapeutic agent for mHSPC administered either as monotherapy or administered concomitant with ADT are of interest.
A radiohybrid theranostics ligand labeled with fluorine-18 and lutetium-177 for fibroblast activation protein-targeted imaging and radionuclide therapy
Authors: Yang Tianhong , Peng Lei , Qiu Jia , He Xingjin , Zhang Dake , Wu Renbo , Liu Jianbo , Zhang Xiangsong , Zha Zhihao
Published: March 2023

Purpose

A series of radiotracers targeting fibroblast activation protein (FAP) with great pharmacokinetics have been developed for cancer diagnosis and therapy. Nevertheless, the use of dominant PET tracers, gallium-68–labeled FAPI derivatives, was limited by the short nuclide half-life and production scale, and the therapeutic tracers exhibited rapid clearance and insufficient tumor retention. In this study, we developed a FAP targeting ligand, LuFL, containing organosilicon-based fluoride acceptor (SiFA) and DOTAGA chelator, capable of labeling fluorine-18 and lutetium-177 in one molecular with simple and highly efficient labeling procedure, to achieve cancer theranostics.

Methods

The precursor LuFL (20) and [natLu]Lu-LuFL (21) were successfully synthesized and labeled with fluorine-18 and lutetium-177 using a simple procedure. A series of cellular assays were performed to characterize the binding affinity and FAP specificity. PET imaging, SPECT imaging, and biodistribution studies were conducted to evaluate pharmacokinetics in HT-1080-FAP tumor-bearing nude mice. A comparison study of [177Lu]Lu-LuFL ([177Lu]21) and [177Lu]Lu-FAPI-04 was carried out in HT-1080-FAP xenografts to determine the cancer therapeutic efficacy.

Results

LuFL (20) and [natLu]Lu-LuFL (21) demonstrated excellent binding affinity towards FAP (IC50: 2.29 ± 1.12 nM and 2.53 ± 1.87 nM), compared to that of FAPI-04 (IC50: 6.69 ± 0.88 nM). In vitro cellular studies showed that 18F-/177Lu-labeled 21 displayed high specific uptake and internalization in HT-1080-FAP cells. Micro-PET, SPECT imaging and biodistribution studies with [18F]/[177Lu]21 revealed higher tumor uptake and longer tumor retention than those of [68 Ga]/[177Lu]Ga/Lu-FAPI-04. The radionuclide therapy studies showed significantly greater inhibition of tumor growth for the [177Lu]21 group, than for the control group and the [177Lu]Lu-FAPI-04 group.

Conclusion

The novel FAPI-based radiotracer containing SiFA and DOTAGA was developed as a theranostics radiopharmaceutical with simple and short labeling process, and showed promising properties including higher cellular uptake, better FAP binding affinity, higher tumor uptake and prolong retention compared to FAPI-04. Preliminary experiments with 18F- and 177Lu-labeled 21 showed promising tumor imaging properties and favorable anti-tumor efficacy.
The prognostic value of patient-reported outcomes in allogeneic hematopoietic stem cell transplantation: exploratory analysis of a randomized nutrition intervention trial
Authors: Gudmundstuen Anne Marte , Efficace Fabio , Tjønnfjord Geir Erland , Skaarud Kristin Joan , Cottone Francesco , Hjermstad Marianne Jensen , Iversen Per Ole
Published: March 2023

Whether patient-reported outcomes (PROs) can predict overall survival (OS) and non-relapse mortality (NRM) among recipients of allogeneic stem cell transplantation (allo-HSCT), is unclear. We performed an exploratory analysis of the prognostic value of patient-reported outcomes (PROs) among 117 recipients of allogeneic stem cell transplantation (allo-HSCT) who participated in a randomized nutrition intervention trial. Cox proportional hazards models were used to investigate possible associations between PROs collected pre-allo-HSCT (baseline) using scores from the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) and 1-year overall survival (OS), whereas logistic regression was used to study associations between these PROs and 1-year non-relapse mortality (NRM). Multivariable analyses indicated that only the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European Bone Marrow Transplantation (EBMT) risk score were associated with 1-year OS. In the multivariable model including clinical-sociodemographic factors for 1-year NRM, our analysis showed that living alone (p=0.009), HCT-CI (p=0.016), EBMT risk score (p=0.002), and stem cell source (p=0.046) could be associated with 1-year NRM. Moreover, in the multivariable model, our analysis showed that only appetite loss from the QLQ-C30 was associated with 1-year NRM (p=0.026). In conclusion, in this specific setting, our analysis suggests that the commonly used HCT-CI and EBMT risk scores could be predictive for both 1-year OS and 1-year NRM, whereas baseline PROs in general were not.
EGFR and MMP-9 are associated with neointimal hyperplasia in systemic-to-pulmonary shunts in children with complex cyanotic heart disease
Authors: Kottmann Philip , Eildermann Katja , Murthi Sarala Raj , Cleuziou Julie , Lemmer Julia , Vitanova Keti , von Stumm Maria , Lehmann Luisa , Hörer Jürgen , Ewert Peter , Sigler Matthias , Lange Rüdiger , Lahm Harald , Dreßen Martina , Lichtner Peter , Wolf Cordula M.
Published: March 2023

Systemic-to-pulmonary shunt malfunction contributes to morbidity in children with complex congenital heart disease after palliative procedure. Neointimal hyperplasia might play a role in the pathogenesis increasing risk for shunt obstruction. The aim was to evaluate the role of epidermal growth factor receptor (EGFR) and matrix-metalloproteinase 9 (MMP-9) in the formation of neointimal within shunts. Immunohistochemistry was performed with anti-EGFR and anti-MMP-9 on shunts removed at follow-up palliative or corrective procedure. Whole-genome single-nucleotide polymorphisms genotyping was performed on DNA extracted from patients´ blood samples and allele frequencies were compared between the group of patients with shunts displaying severe stenosis (≥ 40% of lumen) and the remaining group. Immunohistochemistry detected EGFR and MMP-9 in 24 of 31 shunts, located mainly in the luminal area. Cross-sectional area of EGFR and MMP-9 measured in median 0.19 mm2 (IQR 0.1–0.3 mm2) and 0.04 mm2 (IQR 0.03–0.09 mm2), respectively, and correlated positively with the area of neointimal measured on histology (r = 0.729, p < 0.001 and r = 0.0479, p = 0.018, respectively). There was a trend of inverse correlation between the dose of acetylsalicylic acid and the degree of EGFR, but not MMP-9, expression within neointima. Certain alleles in epidermal growth factor (EGF) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were associated with increased stenosis and neointimal hyperplasia within shunts. EGFR and MMP-9 contribute to neointimal proliferation in SP shunts of children with complex cyanotic heart disease. SP shunts from patients carrying certain risk alleles in the genes encoding for EGF and TIMP-1 displayed increased neointima.
The impact of plasmonic electrodes on the photocarrier extraction of inverted organic bulk heterojunction solar cells
Authors: Kolb Florian , El Gemayel Mirella , Khan Imran , Dostalek Jakub , Trattnig Roman , Sommer Christian , List-Kratochvil Emil J. W.
Published: March 2023

Nano-patterning the semiconducting photoactive layer/back electrode interface of organic photovoltaic devices is a widely accepted approach to enhance the power conversion efficiency through the exploitation of numerous photonic and plasmonic effects. Yet, nano-patterning the semiconductor/metal interface leads to intertwined effects that impact the optical as well as the electrical characteristic of solar cells. In this work we aim to disentangle the optical and electrical effects of a nano-structured semiconductor/metal interface on the device performance. For this, we use an inverted bulk heterojunction P3HT:PCBM solar cell structure, where the nano-patterned photoactive layer/back electrode interface is realized by patterning the active layer with sinusoidal grating profiles bearing a periodicity of 300 nm or 400 nm through imprint lithography while varying the photoactive layer thickness (LPAL) between 90 and 400 nm. The optical and electrical device characteristics of nano-patterned solar cells are compared to the characteristics of control devices, featuring a planar photoactive layer/back electrode interface. We find that patterned solar cells show for an enhanced photocurrent generation for a LPAL above 284 nm, which is not observed when using thinner active layer thicknesses. Simulating the optical characteristic of planar and patterned devices through a finite-difference time-domain approach proves for an increased light absorption in presence of a patterned electrode interface, originating from the excitation of propagating surface plasmon and dielectric waveguide modes. Evaluation of the external quantum efficiency characteristic and the voltage dependent charge extraction characteristics of fabricated planar and patterned solar cells reveals, however, that the increased photocurrents of patterned devices do not stem from an optical enhancement but from an improved charge carrier extraction efficiency in the space charge limited extraction regime. Presented findings clearly demonstrate that the improved charge extraction efficiency of patterned solar cells is linked to the periodic surface corrugation of the (back) electrode interface.
Analysis of clinical features and inflammatory-related molecules with the disease in acute infectious urticaria
Authors: Liu Zhezhang , Al-Quran Lina , Tong Jianbo , Cao Xianwei
Published: March 2023

Acute infectious urticaria, a subset of acute urticaria, with severe persistence wheals and systemic symptoms, response well to corticosteroids treatment in combination with antibiotics. The exact pathogenic mechanisms are not fully understood. In this study, we aim to analyze the different clinical features, compare the level of neutrophil activation, and investigate the expression of inflammatory related cytokine in patients with acute urticaria and acute infectious urticaria. Eighteen patients with acute infectious urticaria and eighteen patients with acute urticaria were included in this study. We analyzed the difference between the clinical features and the serum expressions of pro-inflammatory factors in the two groups, then examined the levels of inflammation-associated cytokines before and after treatment of acute infectious urticaria. Hematoxylin & eosin (HE) staining and immunohistochemistry (IHC) were used to further study the relationship between neutrophil and neutrophil-derived Myeloperoxidase (MPO) of lesions in the two groups. The expression levels of C-reactive protein (CRP), D-dimer, interleukin 6 (IL-6), IL-8 and chemokine ligand 8 (CCL8) in serum were significantly higher in acute infectious urticaria than acute urticaria. In acute infectious urticaria, the serum expression levels of CCL8 were significantly decreased after the treatment, a significant correlation observed between CRP levels and IL-6, both CCL8 and CRP were positively correlated with neutrophil granulocytes. Neutrophils infiltration were not observed by HE stains in two groups, but in IHC stains we found a positive expression of MPO in acute infectious urticaria lesions. Elevated neutrophil in the serum, which is associated with the levels of IL-8 & CCL8, and positively expressed MPO in lesions, may be involved in the pathogenic mechanism of acute infectious urticaria.
Identification of linear time-varying dynamic systems based on the WKB method
Authors: Chen Tengfei , Sorokin Vladislav , Tang Lihua , Chen Guoping , He Huan
Published: March 2023

This work proposes a new parameter identification method based on the Wentzel-Kramers-Brillouin (WKB) approximation for slow linear time-varying (LTV) dynamic systems. The considered time period is divided into a series of short time windows. In each time window, the assumption of “short time linearly varying” parameters is employed, and a nonlinear optimization problem is solved using the WKB results for the slow LTV dynamic system. A search algorithm is developed to find the optimal solution. In the identification process, only one type of response signal (displacement, velocity or acceleration) is required. Thus, numerical differentiation or integration of the measured signal, which leads to truncation or cumulative errors in noise environment, is avoided. The accuracy and robustness of the new identification method are validated by applying it to a particular LTV system with time-varying stiffness.
Gamma oscillations provide insights into cortical circuit development
Authors: Bitzenhofer Sebastian H.
Published: March 2023

Rhythmic coordination in gamma oscillations provides temporal structure to neuronal activity. Gamma oscillations are commonly observed in the mammalian cerebral cortex, are altered early on in several neuropsychiatric disorders, and provide insights into the development of underlying cortical networks. However, a lack of knowledge on the developmental trajectory of gamma oscillations prevented the combination of findings from the immature and the adult brain. This review is intended to provide an overview on the development of cortical gamma oscillations, the maturation of the underlying network, and the implications for cortical function and dysfunction. The majority of information is drawn from work in rodents with particular emphasis on the prefrontal cortex, the developmental trajectory of gamma oscillations, and potential implications for neuropsychiatric disorders. Current evidence supports the idea that fast oscillations during development are indeed an immature form of adult gamma oscillations and can help us understand the pathology of neuropsychiatric disorders.
Heart rate and respiratory rate in predicting risk of serious bacterial infection in febrile children given antipyretics: prospective observational study
Authors: Wittmann Stefanie , Jorgensen Rikke , Oostenbrink Rianne , Moll Henriette , Herberg Jethro , Levin Mike , Maconochie Ian , Nijman Ruud
Published: March 2023

Clinical algorithms used in the assessment of febrile children in the Paediatric Emergency Departments are commonly based on threshold values for vital signs, which in children with fever are often outside the normal range. Our aim was to assess the diagnostic value of heart and respiratory rate for serious bacterial infection (SBI) in children after temperature lowering following administration of antipyretics. A prospective cohort of children presenting with fever between June 2014 and March 2015 at the Paediatric Emergency Department of a large teaching hospital in London, UK, was performed. Seven hundred forty children aged 1 month–16 years presenting with a fever and ≥ 1 warning signs of SBI given antipyretics were included. Tachycardia or tachypnoea were defined by different threshold values: (a) APLS threshold values, (b) age-specific and temperature-adjusted centiles charts and (c) relative difference in z-score. SBI was defined by a composite reference standard (cultures from a sterile site, microbiology and virology results, radiological abnormalities, expert panel). Persistent tachypnoea after body temperature lowering was an important predictor of SBI (OR 1.92, 95% CI 1.15, 3.30). This effect was only observed for pneumonia but not other SBIs. Threshold values for tachypnoea > 97th centile at repeat measurement achieved high specificity (0.95 (0.93, 0.96)) and positive likelihood ratios (LR + 3.25 (1.73, 6.11)) and may be useful for ruling in SBI, specifically pneumonia. Persistent tachycardia was not an independent predictor of SBI and had limited value as a diagnostic test.

  Conclusion: Among children given antipyretics, tachypnoea at repeat measurement had some value in predicting SBI and was useful to rule in pneumonia. The diagnostic value of tachycardia was poor. Overreliance on heart rate as a diagnostic feature following body temperature lowering may not be justified to facilitate safe discharge.

What is Known:• Abnormal vital signs at triage have limited value as a diagnostic test to identify children with SBI, and fever alters the specificity of commonly used threshold values for vital signs.• The observed temperature response after antipyretics is not a clinically useful indicator to differentiate the cause of febrile illness.

What is New:• Persistent tachycardia following reduction in body temperature was not associated with an increased risk of SBI and of poor value as a diagnostic test, whilst persistent tachypnoea may indicate the presence of pneumonia.
Plant species composition and local habitat conditions as primary determinants of terrestrial arthropod assemblages
Authors: Tobisch Cynthia , Rojas-Botero Sandra , Uhler Johannes , Müller Jörg , Kollmann Johannes , Moning Christoph , Brändle Martin , Gossner Martin M. , Redlich Sarah , Zhang Jie , Steffan-Dewenter Ingolf , Benjamin Caryl , Englmeier Jana , Fricke Ute , Ganuza Cristina , Haensel Maria , Riebl Rebekka , Uphus Lars , Ewald Jörg
Published: March 2023

Arthropods respond to vegetation in multiple ways since plants provide habitat and food resources and indicate local abiotic conditions. However, the relative importance of these factors for arthropod assemblages is less well understood. We aimed to disentangle the effects of plant species composition and environmental drivers on arthropod taxonomic composition and to assess which aspects of vegetation contribute to the relationships between plant and arthropod assemblages. In a multi-scale field study in Southern Germany, we sampled vascular plants and terrestrial arthropods in typical habitats of temperate landscapes. We compared independent and shared effects of vegetation and abiotic predictors on arthropod composition distinguishing between four large orders (Lepidoptera, Coleoptera, Hymenoptera, Diptera), and five functional groups (herbivores, pollinators, predators, parasitoids, detritivores). Across all investigated groups, plant species composition explained the major fraction of variation in arthropod composition, while land-cover composition was another important predictor. Moreover, the local habitat conditions depicted by the indicator values of the plant communities were more important for arthropod composition than trophic relationships between certain plant and arthropod species. Among trophic groups, predators showed the strongest response to plant species composition, while responses of herbivores and pollinators were stronger than those of parasitoids and detritivores. Our results highlight the relevance of plant community composition for terrestrial arthropod assemblages across multiple taxa and trophic levels and emphasize the value of plants as a proxy for characterizing habitat conditions that are hardly accessible to direct environmental measurements.
Cross-entropy boosted CRO-SL for optimal power flow in smart grids
Authors: Marcelino C. G. , Pérez-Aracil J. , Wanner E. F. , Jiménez-Fernández S. , Leite G. M. C. , Salcedo-Sanz S.
Published: March 2023

Optimal power flow (OPF) is a complex, highly nonlinear, NP-hard optimization problem, in which the goal is to determine the optimal operational parameters of a power-related system (in many cases a type of smart or micro grid) which guarantee an economic and effective power dispatch. In recent years, a number of approaches based on metaheuristics algorithms have been proposed to solve OPF problems. In this paper, we propose the use of the Cross-Entropy (CE) method as a first step depth search operator to assist population-based evolutionary methods in the framework of an OPF problem. Specifically, a new variant of the Coral Reefs Optimization with Substrate Layers algorithm boosted with CE method (CE+CRO-SL) is presented in this work. We have adopted the IEEE 57-Bus System as a test scenario which, by default, has seven thermal generators for power production for the grid. We have modified this system by replacing three thermal generators with renewable source generators, in order to consider a smart grid approach with renewable energy production. The performance of CE+CRO-SL in this particular case study scenario has been compared with that of well-known techniques such as population’s methods CMA-ES and EPSO (both boosted with CE). The results obtained indicate that CE+CRO-SL showed a superior performance than the alternative techniques in terms of efficiency and accuracy. This is justified by its greater exploration capacity, since it has internally operations coming from different heuristics, thus surpassing the performance of classic methods. Moreover, in a projection analysis, the CE+CRO-SL provides a profit of millions of dollars per month in all cases tested considering the modified version of the IEEE 57-Bus smart grid system.
Characterizing recurrent infections after one-stage revision for periprosthetic joint infection of the knee: a systematic review of the literature
Authors: Bosco Francesco , Cacciola Giorgio , Giustra Fortunato , Risitano Salvatore , Capella Marcello , Vezza Daniele , Barberis Luca , Cavaliere Pietro , Massè Alessandro , Sabatini Luigi
Published: March 2023

Background

Periprosthetic joint infection (PJI) of the knee represents a severe complication after 1.5% to 2% of primary total knee replacement. Although two-stage revision was considered the gold-standard treatment for PJI of the knee, in the last decades, more studies reported the outcomes of one-stage revisions. This systematic review aims to assess reinfection rate, infection-free survival after reoperation for recurrent infection, and the microorganisms involved in both primary and recurrent infection.

Material and methods

A systematic review of all studies reporting the outcome of one-stage revision for PJI of the knee up to September 2022, according to PRISMA criteria and AMSTAR2 guidelines, was performed. Patient demographics, clinical, surgical, and postoperative data were recorded. PROSPERO ID: CRD42022362767.

Results

Eighteen studies with a total of 881 one-stage revisions for PJI of the knee were analyzed. A reinfection rate of 12.2% after an average follow-up of 57.6 months was reported. The most frequent causative microorganism were gram-positive bacteria (71.1%), gram-negative bacteria (7.1%), and polymicrobial infections (8%). The average postoperative knee society score was 81.5, and the average postoperative knee function score was 74.2. The infection-free survival after treatment for recurrent infection was 92.1%. The causative microorganisms at reinfections differed significantly from the primary infection (gram-positive 44.4%, gram-negative 11.1%).

Conclusion

Patients who underwent a one-stage revision for PJI of the knee showed a reinfection rate lower or comparable to other surgical treatments as two-stage or DAIR (debridement, antibiotics, and implant retention). Reoperation for reinfection demonstrates a lower success compared to one-stage revision. Moreover, microbiology differs between primary infection and recurrent infection.

Level of evidence Level IV.
Effectiveness of conservative instrumentation in root canal disinfection
Authors: Usta Sıla Nur , Solana Carmen , Ruiz-Linares Matilde , Baca Pilar , Ferrer-Luque Carmen María , Cabeo Monica , Arias-Moliz Maria Teresa
Published: March 2023

Objectives

The impact of conservative instrumentation on the disinfection of root canals with different curvatures has not yet been determined. This ex vivo study aimed to evaluate and compare the effect of conservative instrumentation with TruNatomy (TN) and Rotate and a conventional rotary system, ProTaper Gold (PTG), on root canal disinfection during chemomechanical preparation of straight and curved canals.

Materials and methods

Ninety mandibular molars with straight (n = 45) and curved (n = 45) mesiobuccal root canals were contaminated with polymicrobial clinical samples. Teeth were divided into three subgroups (n = 14) according to the file systems and the curvature. Canals were instrumented with TN, Rotate, and PTG, respectively. Sodium hypochlorite and EDTA were used as irrigants. Intracanal samples were taken before (S1) and after (S2) instrumentation. Six uninfected teeth were used as negative controls. The bacterial reduction between S1 and S2 was measured by ATP assay, flow cytometry, and culture methods. Kruskal–Wallis and ANOVA tests were followed by the Duncan post hoc test (p < 0.05).

Results

Bacterial reduction percentages were similar for the three file systems in straight canals (p > 0.05). However, PTG showed a lower reduction percentage of intact membrane cells in flow cytometry than TN and Rotate (p = 0.036). For the curved canals, no significant differences were obtained (p > 0.05).

Conclusion

Conservative instrumentation of straight and curved canals using TN and Rotate files resulted in similar bacterial reduction compared to PTG.

Clinical relevance

The disinfection efficacy of conservative instrumentation is similar to conventional instrumentation in straight and curved root canals.
Composite grafts made of polycaprolactone fiber mats and oil-based calcium phosphate cement pastes for the reconstruction of cranial and maxillofacial defects
Authors: Fuchs Andreas , Bartolf-Kopp Michael , Böhm Hartmut , Straub Anton , Kübler Alexander C. , Linz Christian , Gbureck Uwe
Published: March 2023

Objectives

Synthetic bone substitutes which can be adapted preoperatively and patient specific may be helpful in various bony defects in the field of oral- and maxillofacial surgery. For this purpose, composite grafts made of self-setting and oil-based calcium phosphate cement (CPC) pastes, which were reinforced with 3D-printed polycaprolactone (PCL) fiber mats were manufactured.

Materials and methods

Bone defect models were acquired using patient data from real defect situations of patients from our clinic. Using a mirror imaging technique, templates of the defect situation were fabricated via a commercially available 3D-printing system. The composite grafts were assembled layer by layer, aligned on top of these templates and fitted into the defect situation. Besides, PCL-reinforced CPC samples were evaluated regarding their structural and mechanical properties via X-ray diffraction (XRD), infrared (IR) spectroscopy, scanning electron microscopy (SEM), and 3-point-bending testing.

Results

The process sequence including data acquisition, template fabrication, and manufacturing of patient specific implants proved to be accurate and uncomplicated. The individual implants consisting mainly of hydroxyapatite and tetracalcium phosphate displayed good processability and a high precision of fit. The mechanical properties of the CPC cements in terms of maximum force and stress load to material fatigue were not negatively affected by the PCL fiber reinforcement, whereas clinical handling properties increased remarkably.

Conclusion

PCL fiber reinforcement of CPC cements enables the production of very freely modelable three-dimensional implants with adequate chemical and mechanical properties for bone replacement applications.

Clinical relevance

The complex bone morphology in the region of the facial skull often poses a great challenge for a sufficient reconstruction of bony defects. A full-fledged bone replacement here often requires the replication of filigree three-dimensional structures partly without support from the surrounding tissue. With regard to this problem, the combination of smooth 3D-printed fiber mats and oil-based CPC pastes represents a promising method for fabricating patient specific degradable implants for the treatment of various craniofacial bone defects.
Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review
Authors: Rice Lauren J. , Cannon Lisa , Dadlani Navin , Cheung Melissa Mei Yin , Einfeld Stewart L. , Efron Daryl , Dossetor David R. , Elliott Elizabeth J.
Published: March 2023

A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected neuropsychiatric or neurodevelopmental conditions. Risk of bias and quality of evidence was assessed for each article. Of 4466 articles screened, 18 were eligible for inclusion, addressing eight conditions (anxiety disorders (n = 1); autism spectrum disorder (n = 5); foetal alcohol spectrum disorder (n = 1); fragile X syndrome (n = 2); intellectual disability (n = 1); mood disorders (n = 2); post-traumatic stress disorder (n = 3); and Tourette syndrome (n = 3)). Only one randomised controlled trial (RCT) was identified. The remaining seventeen articles included one open-label trial, three uncontrolled before-and-after trials, two case series and 11 case reports, thus the risk of bias was high. Despite growing community and scientific interest, our systematic review identified limited and generally poor-quality evidence for the efficacy of CBP in neuropsychiatric and neurodevelopmental disorders in children and adolescents. Large rigorous RCTs are required to inform clinical care. In the meantime, clinicians must balance patient expectations with the limited evidence available.
Import ban and clean air: estimating the effect of China’s waste import ban on ozone pollution
Authors: Li Jinsong , Takeuchi Kenji
Published: March 2023

In this study, we investigate the effects of the ban on imports of plastic waste on local air quality in China. Using city-level daily ozone concentrations, we examine whether the pollution levels differ after the implementation of the import ban. The results demonstrate that the daily ozone concentration was reduced by 2.8% in treatment areas after the import ban. Additional analyses also suggest that the effect of the ban was larger during the later period and in coastal cities with ports while the effect of the ban might get weak in the long run. These findings highlight the effectiveness of policies that reduce the availability of inputs for pollutive activities.
Meningitis-retention syndrome: a review and update of an unrecognized clinical condition
Authors: Pellegrino Francesco , Funiciello Elisa , Pruccoli Giulia , Silvestro Erika , Scolfaro Carlo , Mignone Federica , Tocchet Aba , Roasio Luca , Garazzino Silvia
Published: March 2023

Objectives

We summarized
the clinical and radiological characteristics of meningitis-retention syndrome (MRS), its therapeutic options, and urological outcome, to better understand the pathogenesis of this syndrome and to evaluate the effectiveness of corticosteroids in reducing the period of urinary retention.

Methods

We reported a new case of MRS in a male adolescent. We also reviewed the previously 28 reported cases of MRS, collected from inception up to September 2022.

Results

MRS is characterized by aseptic meningitis and urinary retention. The mean length of the interval between the onset of the neurological signs and the urinary retention was 6.4 days. In most cases, no pathogens were isolated in cerebrospinal fluid, except for 6 cases in which Herpesviruses were detected. The urodynamic study resulted in a detrusor underactivity, with a mean period for urination recovery of 4.5 weeks, regardless of therapies.

Discussion

Neurophysiological studies and electromyographic examination are not pathological, distinguishing MRS from polyneuropathies. Although there are no encephalitic symptoms or signs, and the magnetic resonance is often normal, MRS may represent a mild form of acute disseminated encephalomyelitis, without radiological detectable medullary involvement, due to the prompt use of steroids. It is believed that MRS is a self-limited disease, and no evidence suggests the effectiveness of steroids, antibiotics, and antiviral treatment in its clinical course.
Effect of femtosecond laser interaction with human fibroblasts: a preliminary study
Authors: Zaki Ewiss M. A. , Mahmoud M. A. , Steiner R.
Published: March 2023

In in vitro methods and cell culture models, femtosecond (fs) laser interaction has been employed to assess its effect on the proliferation and morphology of human skin fibroblasts. We cultured a primary human skin fibroblast cell line on a glass plate, passages 17–23. The cells were irradiated with a 90-fs laser at a wavelength of 800 nm and a repetition rate of 82 MHz. The target received an average power of 320 mW for 5, 20, and 100 s, corresponding to the radiation exposures of 22.6, 90.6, and 452.9 J/cm2, respectively. Using a laser scanning microscopy technique, the photon densities were measured to be 6.4 × 1018, 2.6 × 1019, and 1.3 × 1020 photons/cm2 in a spot area of 0.07 cm2; the recorded spectra were obtained from the laser interaction after 0.00, 1.00, 25.00, and 45.00 h. The cell count and morphological changes showed that the cultured cells were affected by laser irradiation under photon stress; some fibroblasts were killed, while others were injured and survived. We discovered evidence of the formation of several coenzyme compounds, such as flavin (500–600 nm), lipopigments (600–750 nm), and porphyrin (500–700 nm). This study is motivated by the future development of a novel, ultra-short fs laser system and the need to develop a basic in vitro understanding of photon–human cell interaction. The cell proliferation indicated that cells are partly killed or wounded. The exposure of fibroblasts to fs laser fluence up to 450 J/cm2 accelerates cell growth of the viable residual cell.
Curvature properties of 3-$$(\alpha ,\delta )$$-Sasaki manifolds
Authors: Agricola Ilka , Dileo Giulia , Stecker Leander
Published: March 2023

We investigate curvature properties of 3-$$(\alpha ,\delta )$$

(
α
,
δ
)

-Sasaki manifolds, a special class of almost 3-contact metric manifolds generalizing 3-Sasaki manifolds (corresponding to $$\alpha =\delta =1$$

α
=
δ
=
1

) that admit a canonical metric connection with skew torsion and define a Riemannian submersion over a quaternionic Kähler manifold with vanishing, positive or negative scalar curvature, according to $$\delta =0$$

δ
=
0

, $$\alpha \delta >0$$

α
δ
>
0

or $$\alpha \delta <0$$

α
δ
<
0

. We shall investigate both the Riemannian curvature and the curvature of the canonical connection, with particular focus on their curvature operators, regarded as symmetric endomorphisms of the space of 2-forms. We describe their spectrum, find distinguished eigenforms, and study the conditions of strongly definite curvature in the sense of Thorpe.
Investigating the effects of microstructural changes induced by myocardial infarction on the elastic parameters of the heart
Authors: Miller Laura , Penta Raimondo
Published: March 2023

Within this work, we investigate how physiologically observed microstructural changes induced by myocardial infarction impact the elastic parameters of the heart. We use the LMRP model for poroelastic composites (Miller and Penta in Contin Mech Thermodyn 32:1533–1557, 2020) to describe the microstructure of the myocardium and investigate microstructural changes such as loss of myocyte volume and increased matrix fibrosis as well as increased myocyte volume fraction in the areas surrounding the infarct. We also consider a 3D framework to model the myocardium microstructure with the addition of the intercalated disks, which provide the connections between adjacent myocytes. The results of our simulations agree with the physiological observations that can be made post-infarction. That is, the infarcted heart is much stiffer than the healthy heart but with reperfusion of the tissue it begins to soften. We also observe that with the increase in myocyte volume of the non-damaged myocytes the myocardium also begins to soften. With a measurable stiffness parameter the results of our model simulations could predict the range of porosity (reperfusion) that could help return the heart to the healthy stiffness. It would also be possible to predict the volume of the myocytes in the area surrounding the infarct from the overall stiffness measurements.