bluuebunny/crossref_metadata_2025 huggingface dataset:
Tibial plateau fractures are associated with poor functional outcomes and a low conversion rate to total knee arthroplasty
Authors: Kraml Nikolaus , Haslhofer David J. , Winkler Philipp W. , Stiftinger Julian M. , Heidecke Svenja , Kwasny Oskar , Gotterbarm Tobias , Klasan Antonio
Published: March 2024

Purpose

The aim of this study was to analyse the functional outcome and the conversion rate to total knee arthroplasty (TKA) after surgically treated tibial plateau fractures (TPF).

Methods

All patients undergoing surgical treatment of TPF at a single institution between January 2003 and December 2019 were retrospectively reviewed. The Knee injury and Osteoarthritis Outcome Score (KOOS) and Tegner activity scale (TAS) were collected. The conversion rate to TKA was examined 2, 5, 7 and 10 years after surgical treatment of TPF.

Results

Ninety‐four patients, with a mean follow‐up of 110.6 months (±60.0), were included in the functional outcome assessment. Mean KOOS scores were 75.4 for symptoms, 80.6 for pain, 84.3 for activities of daily living (ADL), 59.5 for sports and 61.3 for QOL. All subscales were significantly lower on the injured side compared with the contralateral leg. Lower KOOS was observed in patients with hardware removal and Schatzker type 5 and 6 injuries. Median TAS was postinjury (4) significantly lower than preinjury (5) (p < 0.001). The conversion rate to TKA was 6.3%, 10.9%, 11.7% and 12.2% after 2,5,7 and 10 years of follow‐up, respectively. Patients undergoing TKA were older than patients with no conversion to TKA (2 years follow‐up 53.8 vs. 64.5 years, p = 0.026).

Conclusion

TPFs decrease the function of the knee when compared with the contralateral side and to the preoperative condition. Bicondylar fractures are associated with worse functional outcomes. A conversion rate to TKA of 12.2% was found at 10 years follow‐up.

Level of Evidence

Level III.
Effect of nonsteroidal anti‐inflammatory drugs (aspirin and naproxen) on inflammation‐associated proteomic profiles in mouse plasma and prostate during TMPRSS2‐ERG (fusion)‐driven prostate carcinogenesis
Authors: Prasad Ram Raj , Mishra Neha , Kant Rama , Fox Jennifer T. , Shoemaker Robert H. , Agarwal Chapla , Raina Komal , Agarwal Rajesh
Published: March 2024

Recent preclinical studies have shown that the intake of nonsteroidal anti‐inflammatory drugs (NSAIDs) aspirin and naproxen could be an effective intervention strategy against TMPRSS2‐ERG fusion‐driven prostate tumorigenesis. Herein, as a follow‐up mechanistic study, employing TMPRSS2‐ERG (fusion) positive tumors and plasma from TMPRSS2‐ERG. Ptenflox/flox mice, we profiled the stage specific proteomic changes (focused on inflammatory circulating and prostate tissue/tumor‐specific cytokines, chemokines, and growth factors/growth signaling‐associated molecules) that contribute to prostate cancer (PCa) growth and progression in the TMPRSS2‐ERG fusion‐driven mouse model of tumorigenesis. In addition, the association of the protective effects of NSAIDs (aspirin 1400 ppm and naproxen 400 ppm) with the modulation of these specific molecular pathways was determined. A sandwich Elisa based membrane array‐proteome profiler identifying 111 distinct signaling molecules was employed. Overall, the plasma and prostate tissue sample analyses identified 54 significant and differentially expressed cytokines, chemokines, and growth factors/growth signaling‐associated molecules between PCa afflicted mice (TMPRSS2‐ERG. Ptenflox/flox, age‐matched noncancerous controls, NSAIDs‐supplemented and no‐drug controls). Bioinformatic analysis of the array outcomes indicated that the protective effect of NSAIDs was associated with reduced expression of (a) tumor promoting inflammatory molecules (M‐CSF, IL‐33, CCL22, CCL12, CX3CL1, CHI3L1, and CD93), (b) growth factors‐ growth signaling‐associated molecules (Chemerin, FGF acidic, Flt‐3 ligand, IGFBP‐5, and PEDF), and (c) tumor microenvironment/stromal remodeling proteins MMP2 and MMP9. Overall, our findings corroborate the pathological findings that protective effects of NSAIDs in TMPSS2‐ERG fusion‐driven prostate tumorigenesis are associated with antiproliferative and anti‐inflammatory effects and possible modulation of the immune cell enriched microenvironment.
Deep learning‐based target decomposition for markerless lung tumor tracking in radiotherapy
Authors: Fu Yabo , Zhang Pengpeng , Fan Qiyong , Cai Weixing , Pham Hai , Rimner Andreas , Cuaron John , Cervino Laura , Moran Jean M. , Li Tianfang , Li Xiang
Published: March 2024

Background

In radiotherapy, real‐time tumor tracking can verify tumor position during beam delivery, guide the radiation beam to target the tumor, and reduce the chance of a geometric miss. Markerless kV x‐ray image‐based tumor tracking is challenging due to the low tumor visibility caused by tumor‐obscuring structures. Developing a new method to enhance tumor visibility for real‐time tumor tracking is essential.

Purpose

To introduce a novel method for markerless kV image‐based tracking of lung tumors via deep learning‐based target decomposition.

Methods

We utilized a conditional Generative Adversarial Network (cGAN), known as Pix2Pix, to build a patient‐specific model and generate the synthetic decomposed target image (sDTI) to enhance tumor visibility on the real‐time kV projection images acquired by the onboard kV imager equipped on modern linear accelerators. We used 4DCT simulation images to generate the digitally reconstructed radiograph (DRR) and DTI image pairs for model training. We augmented the training dataset by randomly shifting the 4DCT in the superior‐inferior, anterior‐posterior, and left‐right directions during the DRR and DTI generation process. We performed real‐time 2D tumor tracking via template matching between the DTI generated from the CT simulation and the sDTI generated from the real‐time kV projection images. We validated the proposed method using nine patients’ datasets with implanted beacons near the tumor.

Results

The sDTI can effectively improve the image contrast around the lung tumors on the kV projection images for the nine patients. With the beacon motion as ground truth, the tracking errors were on average 0.8 ± 0.7 mm in the superior‐inferior (SI) direction and 0.9 ± 0.8 mm in the in‐plane left‐right (IPLR) direction. The percentage of successful tracking, defined as a tracking error less than 2 mm in the SI direction, is 92.2% on the 4312 tested images. The patient‐specific model took approximately 12 h to train. During testing, it took approximately 35 ms to generate one sDTI, and 13 ms to perform the tumor tracking using template matching.

Conclusions

Our method offers the potential solution for nearly real‐time markerless lung tumor tracking. It achieved a high level of accuracy and an impressive tracking rate. Further development of 3D lung tumor tracking is warranted.
Does COVID‐19 cause or worsen LUT dysfunction, what are the mechanisms and possible treatments? ICI‐RS 2023
Authors: Khullar Vik , Lemmon Berni , Acar Omer , Abrams Paul , Vahabi Bahareh
Published: March 2024

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19) and produced a worldwide pandemic in 2020. There have been 770,875,433 confirmed cases and 6,959,316 attributed deaths worldwide until September 19, 2023. The virus can also affect the lower urinary tract (LUT) leading to bladder inflammation and producing lower urinary tract symptoms (LUTS) in both the acute and chronic phases of disease.

Methods

At the 2023 meeting of the International Consultation on Incontinence‐Research Society (ICI‐RS), the literature relating to COVID‐19 and bladder dysfunction was reviewed. The LUTS reported, as well as the pathophysiology of these bladder symptoms, were the subject of considerable discussion. A number of different topics were discussed including lower LUTS reported in COVID‐19, how SARS‐CoV‐2 may infect and affect the urinary tract, and proposed mechanisms for how viral infection result in new, worsened, and in some persisting LUTS.

Conclusions

The workshop discussed the interaction between the virus and the immune system, covering current evidence supporting theories underlying the causes of acute and chronic LUTS related to COVID‐19 infection. Research questions for further investigation were suggested and identified.
A low‐burden, self‐weighing intervention to prevent weight gain in adults with obesity who do not enroll in comprehensive treatment
Authors: McVay Megan A. , Carrera Seoane Montserrat , Rajoria Melinda , Dye Marissa , Marshall Natalie , Muenyi Sofia , Alkanderi Anas , Scotti Kellie B. , Ruiz Jaime , Voils Corrine I. , Ross Kathryn M.
Published: March 2024

Background

For individuals who are eligible but unlikely to join comprehensive weight loss programs, a low burden self‐weighing intervention may be a more acceptable approach to weight management.

Methods

This was a single‐arm feasibility trial of a 12‐month self‐weighing intervention. Participants were healthcare patients with a BMI ≥25 kg/m2 with a weight‐related comorbidity or a BMI >30 kg/m2 who reported lack of interest in joining a comprehensive weight loss program, or did not enroll in a comprehensive program after being provided program information. In the self‐weighing intervention, participants were asked to weigh themselves daily on a cellular connected scale and were sent text messages every other week with tailored weight change feedback, including messages encouraging use of comprehensive programs if weight gain occurred.

Results

Of 86 eligible patients, 39 enrolled (45.3%) in the self‐weighing intervention. Self‐weighing occurred on average 4.6 days/week (SD = 1.4). At 12 months, 12 participants (30.8%) lost ≥3% baseline weight, 11 (28.2%) experienced weight stability (±3% baseline), 6 (15.4%) gained ≥3% of baseline weight, and 10 (25.6%) did not have available weight data to evaluate. Three participants reported joining a weight loss program during the intervention (7.7%). Participants reported high intervention satisfaction in quantitative ratings (4.1 of 5), and qualitative interviews identified areas of satisfaction (e.g., timing and content of text messages) and areas for improvement (e.g., increasing personalization of text messages).

Conclusion

A low‐burden self‐weighing intervention can reach adults with overweight/obesity who would be unlikely to engage in comprehensive weight loss programs; the efficacy of this intervention for preventing weight gain should be further evaluated in a randomized trial.
Biodegradation behavior of poly (lactic acid) samples obtained by three‐dimensional printing: Influence of temperature and pigment presence
Authors: Gonzaga Graziela L. , Babetto Alex S. , Gonçalves Lívia M. G. , Bettini Silvia H. P. , Souza Adriana M. C.
Published: March 2024

In this study, the biodegradation behavior in the soil of natural and pigmented poly (lactic acid) (PLA) plates obtained by three‐dimensional (3D) printing or by compression molding was evaluated by the respirometry method at three different temperatures: 21, 28, and 35°C. PLA samples before and after aerobic biodegradation tests were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and size exclusion chromatography analysis. The increase in test temperature enhanced the biodegradation process. At a test temperature of 35°C, the maximum biodegradation rates of natural PLA and pigmented PLA were 65% and 68% higher, respectively, compared to the maximum biodegradation rate observed at 21°C. DSC and TG analysis indicate that pigmented PLA samples were more susceptible to degradation by hydrolysis. However, the rate of biodegradation efficiency was lower in pigmented PLA samples, with a decrease of 16%, 24%, and 14% at 21, 28, and 35°C, respectively, compared to natural PLA. This behavior indicated that pigment hindered the hydrolysis by‐products absorption by microorganisms. Additionally, the presence of micro voids in PLA samples obtained through 3D printing accelerated the rate of biodegradation efficiency by 32% at 28°C compared to pressed samples.

Highlights

Poly (lactic acid) (PLA) plate biodegradation in soil was analyzed using respirometry method.

Temperature, pigment presence, and sample preparation method were considered.

Higher temperatures enhanced both natural and pigmented PLA biodegradation.

Pigments appeared to act as antimicrobial agents, slowing down the process.

Water presence in the micro voids accelerated hydrolysis and biodegradation.
Achieving bottle‐grade poly(ethylene terephthalate)‐like properties from blends of bottle‐grade and thermoform‐grade poly(ethylene terephthalate)
Authors: Ganapathi Anurag , Abdelwahab Mohamed A , Rabnawaz Muhammad
Published: March 2024

Poly(ethylene terephthalate) (PET), both bottle grade (PET‐B) and thermoform grade (PET‐T), are widely used in the packaging sector. However, only PET‐B is recycled and reused, while PET‐T needs to be separated from recycled PET bales. This study aims to assess the impact of solid‐state polymerization (SSP), chain extension and the combination of chain extension–SSP to transform PET‐B and PET‐T blends into PET‐T‐like material. The intrinsic viscosity (IV) values for PET‐B blends with 10–20 wt% of PET‐T are measured for the samples obtained in this study. The mechanical properties, such as tensile strength, modulus, elongation and impact strength, were also determined. The glass transition temperature, melting temperature, crystallinity and thermal degradation were also investigated. The findings suggest that the combination of SSP and chain extension leads to a significant improvement in IV and tensile strength, while SSP alone is less suitable to offer the desired IV values. © 2024 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.
Impact of obstructive sleep apnea on clinical outcomes of hospitalization due to influenza in children: A propensity score‐matched analysis of the US Nationwide Inpatient Sample 2005–2018
Authors: Wang Yao , Chiu Feng‐Hsiang
Published: March 2024

Background

Previous studies have explored the association between obstructive sleep apnea (OSA) and clinical outcomes of influenza in adults, whereas limited research examined this relationship in pediatric populations. This study aimed to evaluate the clinical impact of OSA on the outcomes of pediatric influenza hospitalizations.

Methods

This was a population‐based, retrospective study. Data of children aged 1–19 years hospitalized for influenza infection were extracted from the United States (US) Nationwide Inpatient Sample Database 2005–2018. Univariable and multivariable regression analyses determined associations between OSA, length of stay (LOS), total hospital costs, pneumonia, and life‐threatening events.

Results

After propensity‐score matching, a total of 2100 children were analyzed. The logistic analysis revealed that children with OSA had a significantly increased LOS (β = 2.29 days; 95% confidence interval, CI: 1.01–3.57, p < .001) and total hospital costs (β = 26.06 thousand dollars; 95% CI: 6.62–45.51, p = .009), and higher odds of pneumonia (aged 6–10 years: odds ratio [OR] = 1.52; 95% CI: 1.01–2.27, p = .043; aged ≥ 11 years: OR = 1.83; 95% CI: 1.33–2.53, p < .001).

Conclusions

During influenza admissions, children with OSA had longer LOS, higher hospital costs, and an increased risk of pneumonia compared to those without OSA. These findings underscore the importance of recognizing and managing OSA in influenza‐related infections among children.
Segmentation and detection of crop pests using novel U‐Net with hybrid deep learning mechanism
Authors: Biradar Nagaveni , Hosalli Girisha
Published: March 2024

OBJECTIVE

In India, agriculture is the backbone of economic sectors because of the increasing demand for agricultural products. However, agricultural production has been affected due to the presence of pests in crops. Several methods were developed to solve the crop pest detection issue, but they failed to achieve better results. Therefore, the proposed study used a new hybrid deep learning mechanism for segmenting and detecting pests in crops.

METHOD

Image collection, pre‐processing, segmentation, and detection are the steps involved in the proposed study. There are three steps involved in pre‐processing: image rescaling, equalized joint histogram based contrast enhancement (Eq‐JH‐CE), and bendlet transform based De‐noising (BT‐D). Next, the pre‐processed images are segmented using the DenseNet‐77 UNet model. In this section, the complexity of the conventional UNet model is mitigated by hybridizing it with the DenseNet‐77 model. Once the segmentation is done with an improved model, the crop pests are detected and classified by proposing a novel Convolutional Slice‐Attention based Gated Recurrent Unit (CS‐AGRU) model. The proposed model is the combination of a convolutional Neural Network (CNN) and a Gated Recurrent Unit (GRU). In order to achieve better accuracy outcomes, the proposed study hybridized these models due to their great efficiency. Also, the slice attention mechanism is applied over the proposed model for fetching relevant feature information and thereby enhancing the computational efficiency. So, pests in the crop are finally detected using the proposed method.

RESULT

The Python programming language is utilized for implementation. The proposed approach shows a better accuracy range of 99.52%, IoU of 99.1%, precision of 98.88%, recall of 99.53%, F1‐score of 99.35%, and FNR of 0.011 compared to existing techniques.

DISCUSSION

Identifying and classifying pests helps farmers anticipate potential threats to their crops. By knowing which pests are prevalent in their region or are likely to infest certain crops, farmers can implement preventive measures to protect their crops, such as planting pest‐resistant varieties, using crop rotation, or deploying traps and barriers. © 2024 Society of Chemical Industry.
Design of a Low‐Cost Electron Acceptor for Highly Efficient Organic Solar Cell through Alkyl Chain Branching Position Manipulation
Authors: Liu Xuefeng , Li Kun , Mei Zhe , Chen Yu , Xie Qian , Li Jiayu , Lu Zijing , Wu Yishi , Liao Qing , An Cunbin , Fu Hongbing
Published: March 2024

The state‐of‐the‐art bulk‐heterojunction (BHJ) organic solar cells (OSCs) typically include expensive fused‐ring electron acceptors, hindering industrialization. Designing low‐cost and highly efficient electron acceptors remains challenging. Herein, two low‐cost electron acceptors (DTB2 and DTB3) based on a conjugated 1,4‐di(thiophen‐2‐yl)benzene (DTB) core and two fluorinated 2‐(3‐oxo‐2,3‐dihydroinden‐1‐ylidene)malononitrile end‐groups are reported. Their only difference is the alkyl chain branching position on the benzene ring. Both acceptors exhibit similar low optical gaps of ≈1.35 eV but different molecular orientations. DTB2 shows an edge‐on arrangement, while DTB3, with a shift in branching positions toward the conjugated backbone, produces a face‐on arrangement. Such molecular orientations are maintained in their BHJ layers after blending with a polymer donor PBQx‐TF. The PBQx‐TF:DTB3 film demonstrates superior BHJ phase‐separation and faster charge carrier generation (0.44 ps) than those of the PBQx‐TF:DTB2 film (50 ps). As a result, the DTB2‐based OSC achieves a modest power conversion efficiency (PCE) of 8.5%. While the DTB3‐based OSC produces an outstanding PCE of 15.3%, which is much higher than those of the reported DTB‐based OSCs. Besides, DTB3 has a figure of merit up to 0.46, higher than the state‐of‐the‐art fused‐ring electron acceptors. This work provides new insights into designing low‐cost and highly efficient electron acceptors.
Numerical Modeling of Melt Flow and Mixing in an Inductively Stirred Ladle and Comparison with Gas and Mechanical Stirring
Authors: Avatar Krishna , Mazumdar Dipak
Published: March 2024

Fluid flow and mixing in an inductively stirred ladle are modeled mathematically. The effect of two modes of electromagnetic stirring on motion is simulated; one produces a predominantly swirling motion (as in mechanical, paddle‐stirred ladle), while the other generates an upwelling, toroidal motion (as in gas‐stirred ladle). Two different ANSYS software programs, namely, Maxwell‐3D and Fluent, are applied to carry out numerical simulations. In the former, 3D Maxwell's equations are solved to estimate, a priori, the distribution of Lorentz force within the melt phase due to the imposed three‐phase, alternating current excitation of copper coils, while in the latter, time‐averaged magnetohydrodynamic (MHD) turbulent flow equations are solved to yield the electromagnetically driven flow field. Model predictions are validated against published results and it is shown that the electromagnetic as well as turbulent‐MHD models developed in this work are robust and perform sufficiently accurately. Finally, numerically predicted results together with relevant published work indicated that at equivalent specific input stirring power and identical vessel shape and volume, mixing is fastest in electromagnetic stirring with a traveling magnetic field (producing an upwelling toroidal motion), followed by mechanical agitation, gas stirring, and electromagnetic stirring with a rotating magnetic field (inducing swirling flow).
Control of Electric Wheelchair by Brain‐Computer Interface Using Mixed Reality and Virtual Sound Source
Authors: Mori Fumina , Sugino Masato , Huang Yunshan , Kotani Kiyoshi , Jimbo Yasuhiko
Published: March 2024

A brain‐computer interface for operating an electric wheelchair (wheelchair BCI) has been studied to support independent living for physically disabled patients. The current wheelchair BCI systems are facing the problem that the wheelchair cannot be moved or rotated to an arbitrary place or direction in a single measurement. To solve this problem, we developed a BCI that uses audiovisual stimuli based on mixed‐reality (MR) and virtual sound sources. During the online analysis, six out of seven participants were able to move or rotate the wheelchair to the target location or direction at a rate higher than the chance level. Thus, our results indicate that audiovisual stimulation with MR and virtual sound sources may be useful for intuitive wheelchair operation. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC.
Integrative analysis of bulk RNA‐seq and scRNA‐seq data indicates the prognostic and immunologic values of SERPINH1 in glioma
Authors: Hou Shiqiang , Chen Yinan , Jin Chunjing , Lin Ning
Published: March 2024

Background

SERPINH1 is abnormally expressed in multiple cancers and is associated with malignant progression. However, few reports detail its role in the etiopathogenesis of glioma. Hence, the aim of this article was to investigate the potential value of SERPINH1 in glioma using an integrative analysis.

Methods

Data of RNA‐seq and scRNA‐seq was obtained and evaluated using online databases. The expression of SERPINH1 was confirmed by qRT‐PCR and immunohistochemistry. The prognostic value of SERPINH1 was evaluated using univariate and multivariate Cox regression analyses. SERPINH1‐related signaling pathways and the interaction of SERPINH1 with immunity were also investigated.

Results

SERPINH1 exhibited a markedly elevated expression in glioma compared to normal brain tissues in the online databases. Similar results were confirmed by qRT‐PCR and immunohistochemistry. SERPINH1 was found to be an independent prognosis factor, and high expression of SERPINH1 indicated poor survival. Moreover, a nomogram was constructed to predict prognosis more accurately and intuitively. GSEA analysis showed that SERPINH1 was involved in seven signaling pathways, including JAK‐STAT pathway. Further analysis indicated SERPINH1 was significantly associated with immunity, especially in low‐grade glioma. Additionally, an examination of scRNA‐seq data revealed that SERPINH1 was primarily expressed in T cells of the CD4+ and CD8+ subsets.

Conclusions

SERPINH1 is a key biomarker of glioma prognosis and is immunologically relevant, which provides additional options for targeted therapy of glioma.
Recovery rates and long‐term olfactory dysfunction following COVID‐19 infection
Authors: Dias Melanie , Shaida Zara , Haloob Nora , Hopkins Claire
Published: March 2024

Objectives

Olfactory dysfunction is one of the most recognized symptoms of COVID‐19, significantly impacting quality of life, particularly in cases where recovery is prolonged. This review aims to explore patterns of olfactory recovery post‐COVID‐19 infection, with particular focus on delayed recovery.

Data Sources

Published literature in the English language, including senior author's own work, online and social media platforms, and patients' anecdotal reports.

Method

A comprehensive review of the literature was undertaken by the authors with guidance from the senior author with expertise in the field of olfaction.

Results

Based on self‐report, an estimated 95% of patients recover their olfactory function within 6 months post‐COVID‐19 infection. However, psychophysical testing detects higher rates of persistent olfactory dysfunction. Recovery has been found to continue for at least 2 years postinfection; negative prognostic indicators include severe olfactory loss in the acute phase, female sex, and older age. Variability in quantitative and qualitative disturbance in prolonged cases likely reflects both peripheral and central pathophysiological mechanisms. Limitations of many of the reviewed studies reflect lack of psychophysical testing and baseline olfactory assessment.

Conclusions

Post‐COVID‐19 olfactory dysfunction remains a significant health and psychosocial burden. Emerging evidence is improving awareness and knowledge among clinicians to better support patients through their olfactory rehabilitation, with hope of recovery after several months or years. Further research is needed to better understand the underlying pathogenesis of delayed recovery, identify at risk individuals earlier in the disease course, and develop therapeutic targets.
Sich selbst beleihen. Anträge und die Verwaltung von Wissenschaftlichkeit
Authors: Lorenz Caspar-Fridolin
Published: March 2024

Der Text verhandelt das Zusammenspiel antragsstellender Wissenschaftler*innen auf der einen Seite und Institutionen, die Drittmittel ausschreiben, auf der anderen Seite. Ausgehend von der Frage nach der Gestaltung dieser Texte und den mit dieser »Antragsprosa« verbundenen Textstrategien, verfolgt der Text die These, dass sich neben den bekannten, die Wissenschaften einschränkenden Folgen der Förderungen auch kooperative Elemente finden lassen, die produktiv auf die Entstehung von wissenschaftlichem Wissen einwirken und in dieser Weise in den Bereich wissenschaftlichen Arbeitens gehören.
Verwaltungsreform?
Authors: Priddat Birger P.
Published: March 2024

Der Text erkundet in 49 Reflexionen, die Möglichkeiten, Funktionen und Konsequenzen von Reformen, die in Verwaltungseinheiten organisiert werden. Dabei blickt er auch auf die dabei entstehenden Programme und Techniken – Karrieren in Ämterbürokratien, Outsourcing, Auditing–, die als Folgen stringenter Logiken mitentstehen und Reformen zu ganz eigenen Entwicklungen nutzen.
The antiviral response triggered by the cGAS/STING pathway is subverted by the foot-and-mouth disease virus proteases
Authors: Sanz Miguel Ángel , Polo Miryam , Rodríguez-Pulido Miguel , Huildore Bommanna Ranjitha , Sáiz Margarita
Published: March 2024

Propagation of viruses requires interaction with host factors in infected cells and repression of innate immune responses triggered by the host viral sensors. Cytosolic DNA sensing pathway of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) is a major component of the antiviral response to DNA viruses, also known to play a relevant role in response to infection by RNA viruses, including foot-and-mouth disease virus (FMDV). Here, we provide supporting evidence of cGAS degradation in swine cells during FMDV infection and show that the two virally encoded proteases, Leader (Lpro) and 3Cpro, target cGAS for cleavage to dampen the cGAS/STING-dependent antiviral response. The specific target sequence sites on swine cGAS were identified as Q140/T141 for the FMDV 3Cpro and the KVKNNLKRQ motif at residues 322–330 for Lpro. Treatment of swine cells with inhibitors of the cGAS/STING pathway or depletion of cGAS promoted viral infection, while overexpression of a mutant cGAS defective for cGAMP synthesis, unlike wild type cGAS, failed to reduce FMDV replication. Our findings reveal a new mechanism of RNA viral antagonism of the cGAS-STING innate immune sensing pathway, based on the redundant degradation of cGAS through the concomitant proteolytic activities of two proteases encoded by an RNA virus, further proving the key role of cGAS in restricting FMDV infection.
Elementary Negative Group Delay Filter Functions
Authors: Nako Julia , Psychalinos Costas , Maundy Brent J. , Elwakil Ahmed S.
Published: March 2024

A theoretical study of the behavior of some elementary first- and second-order functions, which are suitable for realizing negative group delay, is performed in this work. As both the gain and phase responses are simultaneously considered, important derivations related to the actual bandwidth of operation are derived accompanied by useful design tips. The presented theory is supported by simulation and experimental results obtained through the utilization of typical active-RC filter structures, as well as from a field-programmable analog array device.
Patient and Public Involvement am Deutschen Zentrum für Psychische Gesundheit: Erreichtes und Herausforderungen
Authors: Lipinski Silke , Sünkel Ulrike , Totzeck Christina , Dresler Thomas , Baskow Irina , Bea Myriam , Hannig Rüdiger , Dziobek Isabel
Published: March 2024

Hintergrund

Patient and Public Involvement (PPI) beschreibt die Partizipation von Betroffenen und Angehörigen, d. h. Erfahrungsexpert:innen (EE), am Forschungsprozess. PPI ist in Deutschland in der Medizin und klinischen Psychologie wenig verbreitet, eine institutionelle Verankerung fehlt bislang. Die deutschlandweite und zentrumsübergreifende Umsetzung von PPI ist eines der Hauptziele des sich seit Mai 2023 im Aufbau befindenden Deutschen Zentrums für Psychische Gesundheit (DZPG). Partizipation von EE soll im DZPG auf allen Ebenen der Entscheidungsfindung implementiert werden.

Ziele

Der Artikel beschreibt die Anfänge, Entwicklung und Herausforderungen der Umsetzung von Partizipationsstrukturen und -projekten im DZPG. Das zentrale politische PPI-Gremium im DZPG, der Trialogische Zentrumsrat (TZR), hat noch vor dem Beginn der finanziellen Förderung des DZPG in fast dreijähriger Arbeit eine umfassende PPI-Strategie für das DZPG entwickelt. Die Strategie sieht u. a. vor, eine weitreichende Mitsprache für EE in allen Entscheidungsgremien des DZPG zu implementieren, EE als Reviewer in die Begutachtung von Forschungsanträgen einzubeziehen, partizipative Elemente in alle Studien des DZPG zu integrieren und nutzerinitiierte Studien zu fördern. Die Implementierung der Strategie wird durch eine zentrumsübergreifende PPI-Infrastruktur, das Center for PPI, und die wissenschaftlichen PPI-Referent:innen gewährleistet. Zu den Aufgaben des Center for PPI gehört die Unterstützung der Mitsprache der EE sowie u. a. die Entwicklung von Instrumenten und Leitfäden für partizipative Forschung, die Zusammenführung von EE und Forschenden für gemeinsame Projekte sowie die Dokumentation und Qualitätssicherung für Partizipative Forschung.

Zu den besonderen Herausforderungen für die erfolgreiche Umsetzung der PPI-Strategie gehört die geringe Erfahrung mit PPI in Deutschland im Bereich der psychischen Gesundheitsforschung und weitestgehend fehlende strukturelle Implementierung. Derzeit erarbeitete Lösungsstrategien umfassen z. B. Schulungen für Forschende und EE, um die Vorteile und Wege zur Realisierung von PPI zu vermitteln und so gemeinsame Entscheidungsfindung und Forschung zu ermöglichen. Außerdem werden weitreichend der Zugang zu Wissen und Ressourcen für EE geschaffen und einheitliche Vergütungsregeln für EE erarbeitet.

Schlussfolgerungen

Eine PPI-Strategie am DZPG wurde erfolgreich erarbeitet und wird derzeit durch die zentrumsübergreifende Infrastruktur Center for PPI implementiert.
CK2 activity is crucial for proper glucagon expression
Authors: Ampofo Emmanuel , Pack Mandy , Wrublewsky Selina , Boewe Anne S. , Spigelman Aliya F. , Koch Hanna , MacDonald Patrick E. , Laschke Matthias W. , Montenarh Mathias , Götz Claudia
Published: March 2024

Aims/hypothesis

Protein kinase CK2 acts as a negative regulator of insulin expression in pancreatic beta cells. This action is mainly mediated by phosphorylation of the transcription factor pancreatic and duodenal homeobox protein 1 (PDX1). In pancreatic alpha cells, PDX1 acts in a reciprocal fashion on glucagon (GCG) expression. Therefore, we hypothesised that CK2 might positively regulate GCG expression in pancreatic alpha cells.

Methods

We suppressed CK2 kinase activity in αTC1 cells by two pharmacological inhibitors and by the CRISPR/Cas9 technique. Subsequently, we analysed GCG expression and secretion by real-time quantitative RT-PCR, western blot, luciferase assay, ELISA and DNA pull-down assays. We additionally studied paracrine effects on GCG secretion in pseudoislets, isolated murine islets and human islets. In vivo, we examined the effect of CK2 inhibition on blood glucose levels by systemic and alpha cell-specific CK2 inhibition.

Results

We found that CK2 downregulation reduces GCG secretion in the murine alpha cell line αTC1 (e.g. from 1094±124 ng/l to 459±110 ng/l) by the use of the CK2-inhibitor SGC-CK2-1. This was due to a marked decrease in Gcg gene expression through alteration of the binding of paired box protein 6 (PAX6) and transcription factor MafB to the Gcg promoter. The analysis of the underlying mechanisms revealed that both transcription factors are displaced by PDX1. Ex vivo experiments in isolated murine islets and pseudoislets further demonstrated that CK2-mediated reduction in GCG secretion was only slightly affected by the higher insulin secretion after CK2 inhibition. The kidney capsule transplantation model showed the significance of CK2 for GCG expression and secretion in vivo. Finally, CK2 downregulation also reduced the GCG secretion in islets isolated from humans.

Conclusions/interpretation

These novel findings not only indicate an important function of protein kinase CK2 for proper GCG expression but also demonstrate that CK2 may be a promising target for the development of novel glucose-lowering drugs.

Graphical Abstract
The impact of environmental regulation on innovation and international competitiveness
Authors: Fabrizi Andrea , Gentile Marco , Guarini Giulio , Meliciani Valentina
Published: March 2024

The purpose of this paper is to analyze the impact of environmental regulation on innovation and international competitiveness. We test the weak, narrow, and strong versions of Porter's hypotheses by looking at the impact of environmental regulation on exports both directly and indirectly through innovation and by introducing the role of pollution intensity in moderating the impact of stringent regulation on innovation and international competitiveness. Green policies are measured with the OECD Environmental Stringency Policy Index, distinguishing between market, non-market instruments, and technology support policies. Differently from previous papers, we adopt the technology gap approach to trade, which is suitable for relating environmental regulation to trade competitiveness and we apply the simultaneous-equation system econometric model with a moderating factor represented by pollution intensity. The results support the weak and strong versions of Porter’s hypotheses and find that the positive impact of regulation on innovation and exports increases with a country’s pollution intensity, suggesting that green policies, if properly coordinated, can represent a win–win strategy, fostering, at the same time, sustainability and international competitiveness.
Impact of Underweight, Overweight, and Obesity on Health-Related Quality of Life in Children with Tetralogy of Fallot Variants
Authors: Hidestrand Pip , Svensson Birgitta , Simpson Pippa , Liuba Petru , Weismann Constance G.
Published: March 2024

Traditional cardiovascular risk factors put patients with congenital heart disease (CHD) at increased risk for cardiovascular morbidity and mortality. The aim of this study was to evaluate whether body mass index (BMI) is associated with health-related quality of life (HRQoL) in patients with variants of Tetralogy of Fallot (TOF). Patients and parents of children with variants of TOF–CHD were asked to fill out the PedsQL 4.0 questionnaire and provide weight and length. Patients were categorized into low, normal, and high BMI percentiles. Other demographic data were obtained from the Swedish national registry for congenital heart disease (SWEDCON). Statistical analyses included non-parametric Mann–Whitney U test, Fisher exact, and Chi-square tests. Eighty-five patients were included. Twelve were overweight or obese, 57 had a normal BMI, and 16 were underweight. There was a significant difference in age and gender between the groups. Comparing overweight/obese children to those with normal BMI, physical and social functioning were impaired, while emotional and school function were comparable between the groups. This applied to both child and parental assessment. When comparing underweight to normal weight children, school functioning assessed by the parent was the only domain significantly different from patients with a normal BMI. Children with variants of TOF and overweight/obesity have lower HRQoL, particularly in physical and social functioning, while underweight children may have impaired school functioning. We suggest that preventive measures aimed at maintaining a normal weight should be taken early in life to reduce long-term cardiovascular risk in the CHD population.
Rare earth contamination of edible vegetation: Ce, La, and summed REE in fungi
Authors: Falandysz Jerzy , Kilanowicz Anna , Fernandes Alwyn R. , Zhang Ji
Published: March 2024

The increasing and diversified use of rare earth elements (REE) is considered a potential source of pollution of environmental media including soils. This work documents critically overview data on the occurrence of REE in the fruiting bodies of wild and farmed species of edible and medicinal mushrooms, as this was identified as the largest published dataset of REE occurrence in foodstuff. Most of the literature reported occurrences of cerium (Ce) and lanthanum (La), but a number of studies lacked data on all lanthanides. The Ce, La, and summed REE occurrences were assessed through the criteria of environmental geochemistry, analytical chemistry, food toxicology, mushroom systematics, and ecology. Ce and La accumulate similarly in fruiting bodies and are not fractionated during uptake, maintaining the occurrence patterns of their growing substrates. Similarly, there is no credible evidence of variable REE uptake because the evaluated species data show natural, unfractionated patterns in accordance with the Oddo-Harkins’ order of environmental lanthanide occurrence. Thus, lithosphere occurrence patterns of Ce and La as the first and the third most abundant lanthanides are reflected in wild and farmed mushrooms regardless of substrate and show that Ce is around twice more abundant than La. The current state of knowledge provides no evidence that mushroom consumption at these REE occurrence levels poses a health risk either by themselves or when included with other dietary exposure. Macromycetes appear to bio-exclude lanthanides because independently reported bioconcentration factors for different species and collection sites, typically range from < 1 to 0.001. This is reflected in fruiting body concentrations which are four to two orders of magnitude lower than growing substrates.

Key points

•Original REE occurrence patterns in soils/substrates are reflected in mushrooms

•No evidence for the fractionation of REE during uptake by fungi

•Mushrooms bio-exclude REE in fruiting bodies

Graphical Abstract
Vocal and genetic variation between a land-bridge island and mainland populations of the Black-crowned Antshrike (Thamnophilus atrinucha)
Authors: Sedano-Cruz Raul Ernesto , Pérez-Amaya Natalia , Rivera-Gutierrez Hector Fabio
Published: March 2024

Island-mainland systems serve as natural laboratories for studying communication signals. We explored potential divergence in the song of the black-crowned antshrike between Gorgona Island, a land-bridge island off the Pacific coast of Colombia, and several mainland populations. We found that the perching song of this species, the so called loudsong, was distinctly different on Gorgona Island. This differentiation encompassed an increase in frequency bandwidth, a decrease in vocal performance, and a reduction in song duration. All are consistent with documented patterns of divergence observed in avian acoustic signals on oceanic islands. The observed distinctions in loudsong acoustics, including variations in frequency and temporal features, led to the inference that the population on Gorgona Island produces the least complex loudsong dialect across the entire species range. This pattern of how an innate vocalization manifests within a land-bridge island, which was connected to the mainland not long ago, lends support to the Character Release Hypothesis. To ensure an unbiased comparison, we considered genetic clusters and analyzed them by comparing ten acoustic signals between the land-bridge island and several mainland populations. Combined with the gene genealogy, this finding supports the validity of two geographic forms: Thamnophilus atrinucha atrinucha and Thamnophilus atrinucha gorgonae (island). However, they also reveal the existence of additional unrecognized dialects of loudsong that transcend current taxonomic classifications. We provide evidence that challenges the long-standing presumption suggesting minimal intraspecific geographic variation in the vocalization among non-vocal learning species.

Significance statement

Significant evolutionary implications exist for an intriguing pattern of variation of the loudsong behavior in the Black-crowned Antshrike over a land-bridge island. Our gene tree does provide evidence of the enormous haplotypic diversity accumulated in the trans-Andean region long after the final uplift of the northern Andes. The acoustic divergence of the loudsong suggests substantial geographic variation within a non-vocal learning suboscine. Genetic and loudsong divergence on a land-bridge island add to document that evolution of acoustic traits may be relaxed in islands as compared to those observed on the species-rich mainland. The island-mainland system is one of the few definitive biogeographic contexts for understanding evolution of acoustic behavior.
High-intensity focused ultrasound with visually directed power adjustment for focal treatment of localized prostate cancer: systematic review and meta-analysis
Authors: Peretsman Samuel J. , Emberton Mark , Fleshner Neil , Shoji Sunao , Bahler Clinton D. , Miller Larry E.
Published: March 2024

Purpose

To characterize patient outcomes following visually directed high-intensity focused ultrasound (HIFU) for focal treatment of localized prostate cancer.

Methods

We performed a systematic review of cancer-control outcomes and complication rates among men with localized prostate cancer treated with visually directed focal HIFU. Study outcomes were calculated using a random-effects meta-analysis model.

Results

A total of 8 observational studies with 1,819 patients (median age 67 years; prostate-specific antigen 7.1 mg/ml; prostate volume 36 ml) followed over a median of 24 months were included. The mean prostate-specific antigen nadir following visually directed focal HIFU was 2.2 ng/ml (95% CI 0.9–3.5 ng/ml), achieved after a median of 6 months post-treatment. A clinically significant positive biopsy was identified in 19.8% (95% CI 12.4–28.3%) of cases. Salvage treatment rates were 16.2% (95% CI 9.7–23.8%) for focal- or whole-gland treatment, and 8.6% (95% CI 6.1–11.5%) for whole-gland treatment. Complication rates were 16.7% (95% CI 9.9–24.6%) for de novo erectile dysfunction, 6.2% (95% CI 0.0–19.0%) for urinary retention, 3.0% (95% CI 2.1–3.9%) for urinary tract infection, 1.9% (95% CI 0.1–5.3%) for urinary incontinence, and 0.1% (95% CI 0.0–1.4%) for bowel injury.

Conclusion

Limited evidence from eight observational studies demonstrated that visually directed HIFU for focal treatment of localized prostate cancer was associated with a relatively low risk of complications and acceptable cancer control over medium-term follow-up. Comparative, long-term safety and effectiveness results with visually directed focal HIFU are lacking.
Unveiling the challenges of UTUC biopsies and cytology: insights from a global real-world practice study
Authors: Baard Joyce , Cormio Luigi , Dasgupta Ranan , Maruzzi Daniele , Rais-Bahrami Soroush , Serrano Alvaro , Geavlete Bogdan , Giannakopoulos Stilianos , de la Rosette Jean , Laguna Pilar
Published: March 2024

Purpose

Diagnostic ureteroscopy (dURS) is optional in the assessment of patients with upper tract urothelial carcinoma (UTUC) and provides the possibility of obtaining histology.

Methods

To evaluate endoscopic biopsy techniques and outcomes, we assessed data from patients from the CROES-UTUC registry. The registry includes multicenter prospective collected data on diagnosis and management of patients suspected having UTUC.

Results

We assessed 2380 patients from 101 centers. dURS with biopsy was performed in 31.6% of patients. The quality of samples was sufficient for diagnosis in 83.5% of cases. There was no significant association between biopsy techniques and quality (p = 0.458). High-grade biopsy accurately predicted high-grade disease in 95.7% and high-risk stage disease in 86%. In ureteroscopic low-grade tumours, the prediction of subsequent low-grade disease was 66.9% and low-risk stage Ta-disease 35.8%. Ureteroscopic staging correctly predicted non-invasive Ta-disease and ≥ T1 disease in 48.9% and 47.9% of patients, respectively. Cytology outcomes did not provide additional value in predicting tumour grade.

Conclusion

Biopsy results adequately predict high-grade and high-risk disease, but approximately one-third of patients are under-staged. Two-thirds of patients with low-grade URS-biopsy have high-risk stage disease, highlighting the need for improved diagnostics to better assess patient risk and guide treatment decisions.

Clinical trial registration: The study was registered at ClinicalTrials.gov (ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188).