bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecularly imprinted nanogels as synthetic recognition materials for the ultrasensitive detection of periodontal disease biomarkers
Authors: Hix-Janssens Thomas , Davies Julia R. , Turner Nicholas W. , Sellergren Börje , Sullivan Mark V. 
Published: June 2024

AbstractPeriodontal disease affects supporting dental structures and ranks among one of the top most expensive conditions to treat in the world. Moreover, in recent years, the disease has also been linked to cardiovascular and Alzheimer’s diseases. At present, there is a serious lack of accurate diagnostic tools to identify people at severe risk of periodontal disease progression. Porphyromonas gingivalis is often considered one of the most contributing factors towards disease progression. It produces the Arg- and Lys-specific proteases Rgp and Kgp, respectively. Within this work, a short epitope sequence of these proteases is immobilised onto a magnetic nanoparticle platform. These are then used as a template to produce high-affinity, selective molecularly imprinted nanogels, using the common monomers N-tert-butylacrylamide (TBAM), N-isopropyl acrylamide (NIPAM), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). N,N-Methylene bis(acrylamide) (BIS) was used as a crosslinking monomer to form the interconnected polymeric network. The produced nanogels were immobilised onto a planar gold surface and characterised using the optical technique of surface plasmon resonance. They showed high selectivity and affinity towards their template, with affinity constants of 79.4 and 89.7 nM for the Rgp and Kgp epitope nanogels, respectively. From their calibration curves, the theoretical limit of detection was determined to be 1.27 nM for the Rgp nanogels and 2.00 nM for the Kgp nanogels. Furthermore, they also showed excellent selectivity against bacterial culture supernatants E8 (Rgp knockout), K1A (Kgp knockout), and W50-d (wild-type) strains in complex medium of brain heart infusion (BHI).
A novel biomimetic nanoplasmonic sensor for rapid and accurate evaluation of checkpoint inhibitor immunotherapy
Authors: Batool Razia , Soler Maria , Singh Rukmani , Lechuga Laura M. 
Published: June 2024

AbstractImmune checkpoint inhibitors (ICIs) emerged as promising immunotherapies for cancer treatment, harnessing the patient’s immune system to fight and eliminate tumor cells. However, despite their potential and proven efficacies, checkpoint inhibitors still face important challenges such as the tumor heterogeneity and resistance mechanisms, and the complex in vitro testing, which limits their widespread applicability and implementation to treat cancer. To address these challenges, we propose a novel analytical technique utilizing biomimetic label-free nanoplasmonic biosensors for rapid and reliable screening and evaluation of checkpoint inhibitors. We have designed and fabricated a low-density nanostructured plasmonic sensor based on gold nanodisks that enables the direct formation of a functional supported lipid bilayer, which acts as an artificial cell membrane for tumor ligand immobilization. With this biomimetic scaffold, our biosensing approach provides real-time, highly sensitive analysis of immune checkpoint pathways and direct assessment of the blocking effects of monoclonal antibodies in less than 20 min/test. We demonstrate the accuracy of our biomimetic sensor for the study of the programmed cell death protein 1 (PD1) checkpoint pathway, achieving a limit of detection of 6.7 ng/mL for direct PD1/PD-L1 interaction monitoring. Besides, we have performed dose–response inhibition curves for an anti-PD1 monoclonal antibody, obtaining a half maximal inhibitory concentration (IC50) of 0.43 nM, within the same range than those obtained with conventional techniques. Our biomimetic sensor platform combines the potential of plasmonic technologies for rapid label-free analysis with the reliability of cell-based assay in terms of ligand mobility. The biosensor is integrated in a compact user-friendly device for the straightforward implementation in biomedical and pharmaceutical laboratories.
Graphical Abstract
Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0
Authors: Albert Nathalie L. , Preusser Matthias , Traub-Weidinger Tatjana , Tolboom Nelleke , Law Ian , Palmer Joshua D. , Guedj Eric , Furtner Julia , Fraioli Francesco , Huang Raymond Y. , Johnson Derek R. , Deroose Christophe M. , Herrmann Ken , Vogelbaum Michael , Chang Susan , Tonn Joerg-Christian , Weller Michael , Wen Patrick Y. , van den Bent Martin J. , Verger Antoine , Ivanidze Jana , Galldiks Norbert 
Published: June 2024

Abstract
Purpose
To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands.

Methods
This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO).

Results
Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma.

Conclusion
These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576–87). The information provided should be considered in the context of local conditions and regulations.
TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma
Authors: Xue Han-Yue , Wei Fang 
Published: June 2024

AbstractAlthough substantial quantities of potent therapies for multiple myeloma (MM) have been established, MM remains an incurable disease. In recent years, our understanding of the initiation, development, and metastasis of cancers has made a qualitative leap. Cancers attain the abilities to maintain proliferation signals, escape growth inhibitors, resist cell death, induce angiogenesis, and more importantly, escape anti-tumor immunity and reprogram metabolism, which are the hallmarks of cancers. Besides, different cancers have different tumor microenvironments (TME), thus, we pay more attention to the TME in the pathogenesis of MM. Many researchers have identified that myeloma cells interact with the components of TME, which is beneficial for their survival, ultimately causing the formation of immunosuppressive and high-metabolism TME. In the process, transforming growth factor-β (TGF-β), as a pivotal cytokine in the TME, controls various cells’ fates and influences numerous metabolic pathways, including inhibiting immune cells to infiltrate the tumors, suppressing the activation of anti-tumor immune cells, facilitating more immunosuppressive cells, enhancing glucose and glutamine metabolism, dysregulating bone metabolism and so on. Thus, we consider TGF-β as the tumor promoter. However, in healthy cells and the early stage of tumors, it functions as a tumor suppressor. Due to the effect of context dependence, TGF-β has dual roles in TME, which attracts us to further explore whether targeting it can overcome obstacles in the treatment of MM by regulating the progression of myeloma, molecular mechanisms of drug resistance, and various signaling pathways in the immune and metabolic microenvironment. In this review, we predominantly discuss that TGF-β promotes the development of MM by influencing immunity and metabolism.
“How I would like AI used for my imaging”: children and young persons’ perspectives
Authors: Lee Lauren , Salami Raimat Korede , Martin Helena , Shantharam Lavanhya , Thomas Kate , Ashworth Emily , Allan Emma , Yung Ka-Wai , Pauling Cato , Leyden Deirdre , Arthurs Owen J. , Shelmerdine Susan Cheng 
Published: June 2024

Abstract
Objectives
Artificial intelligence (AI) tools are becoming more available in modern healthcare, particularly in radiology, although less attention has been paid to applications for children and young people. In the development of these, it is critical their views are heard.

Materials and methods
A national, online survey was publicised to UK schools, universities and charity partners encouraging any child or young adult to participate. The survey was “live” for one year (June 2022 to 2023). Questions about views of AI in general, and in specific circumstances (e.g. bone fractures) were asked.

Results
One hundred and seventy-one eligible responses were received, with a mean age of 19 years (6–23 years) with representation across all 4 UK nations. Most respondents agreed or strongly agreed they wanted to know the accuracy of an AI tool that was being used (122/171, 71.3%), that accuracy was more important than speed (113/171, 66.1%), and that AI should be used with human oversight (110/171, 64.3%). Many respondents (73/171, 42.7%) felt AI would be more accurate at finding problems on bone X-rays than humans, with almost all respondents who had sustained a missed fracture strongly agreeing with that sentiment (12/14, 85.7%).

Conclusions
Children and young people in our survey had positive views regarding AI, and felt it should be integrated into modern healthcare, but expressed a preference for a “medical professional in the loop” and accuracy of findings over speed. Key themes regarding information on AI performance and governance were raised and should be considered prior to future AI implementation for paediatric healthcare.

Clinical relevance statement
Artificial intelligence (AI) integration into clinical practice must consider all stakeholders, especially paediatric patients who have largely been ignored. Children and young people favour AI involvement with human oversight, seek assurances for safety, accuracy, and clear accountability in case of failures.

Key Points

Paediatric patient’s needs and voices are often overlooked in AI tool design and deployment.

Children and young people approved of AI, if paired with human oversight and reliability.

Children and young people are stakeholders for developing and deploying AI tools in paediatrics.
Preoperative proteinuria correlates with renal function after partial nephrectomy for renal cell carcinoma
Authors: Nicolazzini Michele , Palumbo Carlotta , Porté Francesca , Bondonno Gianmarco , De Angelis Paolo , Del Galdo Maria Teresa , Volpe Alessandro 
Published: June 2024

Abstract
Purpose
Preoperative proteinuria is a prognostic factor of chronic kidney disease (CKD). We assessed the association between preoperative proteinuria and postoperative renal function after partial nephrectomy (PN).

Methods
We retrospectively reviewed our records of patients with a single malignant renal mass who underwent PN between 2000 and 2021. Patients with data on preoperative proteinuria were included. Baseline characteristics and eGFR differences over time between patients with and without proteinuria were evaluated. Univariate and multivariable logistic regression models (LRM) tested for presence of CKDIII or higher at 12-month and at last follow-up.

Results
Two hundred ninety-five patients were included. Twenty-two of them had preoperative proteinuria. No differences of age, smoking status, hypertension or diabetes, tumor size and use of ischemia were observed. Patients with proteinuria had a higher rate of CKD-III at baseline. At a median follow-up of 46.5 months (IQR 19–82), 117 patients developed de novo CKD-III, without differences in the two groups. No differences in decline in eGFR were observed. At univariate LRM, predictors of CKD-III at 12 months after PN were preoperative proteinuria (OR 3.2, 95%CI 1.4–7.8, p = 0.005), age and baseline eGFR, while predictors of CKD-III at last follow-up were age and baseline eGFR. At multivariable LRM, only baseline eGFR predicted CKD-III at 12-month and at last-follow-up.

Conclusions
Preoperative eGFR is the only independent predictor of long-term renal function after PN. Preoperative proteinuria correlates with renal function at 12 months. Proteinuria should be assessed before PN to identify patients at higher risk of renal functional deterioration in the 12 months following PN.
HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion
Authors: Liu Yu , Wu Ruifang , Li Changzhong , Duan Lvfang , Wei Lihui , Li Ruizhen 
Published: June 2024

Abstract
Purpose
We aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL).

Methods
Retrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48–72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2.

Results
The mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT.

Conclusions
HiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.
The influence of cooling on biomechanical time since death estimations using ovine brain tissue
Authors: Zwirner Johann , Devananthan Pavithran , Docherty Paul D. , Ondruschka Benjamin , Kabaliuk Natalia 
Published: June 2024

AbstractThe significance of biomechanical analyses for forensic time since death estimations has recently been demonstrated. Previous biomechanical analyses successfully discriminated post-mortem brain tissue from tissue with a post-mortem interval of at least one day when held at 20 °C. However, the practical utility of such analyses beyond day one at 20 °C was limited. This study investigates the storage, loss, and complex shear modulus of various brain regions in sheep stored at 4 °C in 24-hour intervals over four days post-mortem using rheometry tests. The aim is to identify the critical biomechanical tissue property values to predict post-mortem time and assess the temperature sensitivity of the rheometry method by comparing results to recent findings at 20 °C. Thirty sheep brains were examined, including the frontal lobe, parietal lobe, anterior and posterior deep brain, superior colliculi, pons, medulla, and cerebellum. Rheometry tests were conducted, and receiver operator characteristic analyses were employed to establish cut-off values. At 4 °C storage, all investigated biomechanical properties of the examined brain regions remained stable for at least one day post-mortem. Using cerebellar samples stored at 4 °C, a post-mortem interval of at least two days could be determined with excellent diagnostic ability. Complex shear modulus values below 1435 Pa or storage modulus values below 1313 Pa allowed prediction of two or more days post-mortem. Comparisons between 4 °C and 20 °C revealed brain region-specific results. For instance, the complex shear moduli of the anterior deep brain at 4 °C were significantly higher on all individual testing days when compared to 20 °C. In contrast, the combined medulla and pons samples were similar on each day. Rheometry testing of brain tissue consistently stored at 4 °C since death proved valuable for forensic time since death estimations starting from two days after death.
Predicting daily recovery during long-term endurance training using machine learning analysis
Authors: Rothschild Jeffrey A. , Stewart Tom , Kilding Andrew E. , Plews Daniel J. 
Published: June 2024

Abstract
Purpose
The aim of this study was to determine if machine learning models could predict the perceived morning recovery status (AM PRS) and daily change in heart rate variability (HRV change) of endurance athletes based on training, dietary intake, sleep, HRV, and subjective well-being measures.

Methods
Self-selected nutrition intake, exercise training, sleep habits, HRV, and subjective well-being of 43 endurance athletes ranging from professional to recreationally trained were monitored daily for 12 weeks (3572 days of tracking). Global and individualized models were constructed using machine learning techniques, with the single best algorithm chosen for each model. The model performance was compared with a baseline intercept-only model.

Results
Prediction error (root mean square error [RMSE]) was lower than baseline for the group models (11.8 vs. 14.1 and 0.22 vs. 0.29 for AM PRS and HRV change, respectively). At the individual level, prediction accuracy outperformed the baseline model but varied greatly across participants (RMSE range 5.5–23.6 and 0.05–0.44 for AM PRS and HRV change, respectively).

Conclusion
At the group level, daily recovery measures can be predicted based on commonly measured variables, with a small subset of variables providing most of the predictive power. However, at the individual level, the key variables may vary, and additional data may be needed to improve the prediction accuracy.
Status quo of operative training in emergency surgery in Germany – results of a survey
Authors: Wachter N. , Güsgen C. , Geis C. , Penzkofer L.S. , Oldhafer K. , Willms A.G. , Huber Tobias 
Published: June 2024

Abstract
Background
Emergencies and emergency surgeries are a central part of everyday surgical care in Germany. However, it is unclear how emergency surgery is practically trained in clinics on a daily basis and what training concept is underlying. Therefore, the aim of this survey study was to capture the status quo of emergency surgical training of German general and visceral surgeons.

Methods
The members of the German Society for General and Visceral Surgery were surveyed online (n = 5281). The questionnaire included demographic data and expertise in surgery and assistance in emergency surgery regarding common emergency surgical operations. In addition, further training measures in emergency surgery and their support by employers were queried.

Results
Only complete questionnaires (n = 184, response rate 3.5%) were included in the analysis. Most participants were in training (n = 69; 38%), followed by senior physicians (n = 52; 29%), specialists (n = 31; 17%) and chief physicians (n = 30; 17%). 64% of the participants were employed at university hospitals or maximum care hospitals. Regarding further training opportunities, in-clinic shock room training was most frequently used. Outside of their own clinic, the ATLS course was most frequently mentioned. Operations for cholecystitis and appendicitis as well as emergency stoma procedures are the most common emergency procedures. There was a strong difference in the frequency of operated cases depending on the level of training. For operations to treat acute abdominal traumas (hemostasis of liver and spleen, packing) as well as outside of visceral surgery, only low competence was reported. Over 90% of survey participants consider emergency surgery to be an indispensable core competence. Neither in the old (76%) nor in the new training regulations (47%) is emergency surgery adequately represented according to the participants’ assessment. There was a significantly lower prevalence of the “sub-steps concept” in emergency surgery at 38% compared to elective surgery (44%). Important elements of imparting skills in emergency surgery are simulation and courses as well as operative sub-steps, according to the majority of survey participants.

Conclusion
The results show that general and visceral surgeons in Germany are introduced to emergency surgery too little structured during further training and at specialist level. The survey participants had, as expected, hardly any experience in emergency surgery outside of visceral surgery but surprisingly also little experience in visceral surgical trauma care. There is a need to discuss the future organization of emergency surgical training. Adequate simulation structures and extracurricular courses could contribute to an improvement in this respect.
Lysozyme: an endogenous antimicrobial protein with potent activity against extracellular, but not intracellular Mycobacterium tuberculosis
Authors: Maier Felix Immanuel , Klinger David , Grieshober Mark , Noschka Reiner , Rodriguez Armando , Wiese Sebastian , Forssmann Wolf-Georg , Ständker Ludger , Stenger Steffen 
Published: June 2024

AbstractEndogenous antimicrobial peptides (AMPs) play a key role in the host defense against pathogens. AMPs attack pathogens preferentially at the site of entry to prevent invasive infection. Mycobacterium tuberculosis (Mtb) enters its host via the airways. AMPs released into the airways are therefore likely candidates to contribute to the clearance of Mtb immediately after infection. Since lysozyme is detectable in airway secretions, we evaluated its antimicrobial activity against Mtb. We demonstrate that lysozyme inhibits the growth of extracellular Mtb, including isoniazid-resistant strains. Lysozyme also inhibited the growth of non-tuberculous mycobacteria. Even though lysozyme entered Mtb-infected human macrophages and co-localized with the pathogen we did not observe antimicrobial activity. This observation was unlikely related to the large size of lysozyme (14.74 kDa) because a smaller lysozyme-derived peptide also co-localized with Mtb without affecting the viability. To evaluate whether the activity of lysozyme against extracellular Mtb could be relevant in vivo, we incubated Mtb with fractions of human serum and screened for antimicrobial activity. After several rounds of sub-fractionation, we identified a highly active fraction-component as lysozyme by mass spectrometry. In summary, our results identify lysozyme as an antimycobacterial protein that is detectable as an active compound in human serum. Our results demonstrate that the activity of AMPs against extracellular bacilli does not predict efficacy against intracellular pathogens despite co-localization within the macrophage. Ongoing experiments are designed to unravel peptide modifications that occur in the intracellular space and interfere with the deleterious activity of lysozyme in the extracellular environment.